doc_id sent_index relation_id relation trigger trigger_offset arg_num arg_head arg_protein arg_domain arg_site arg_sugar arg_head_offset arg_base_np arg_base_np_offset arg_np arg_np_offset sent_text 25374123 0 0 theme tandem 87:92 arg1 spectrometry 99:110 tandem mass spectrometry 87:110 tandem mass spectrometry with immunoprecipitation 87:135 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 4 1 theme tryptic 772:778 arg1 N-glycopeptides 780:794 tryptic N-glycopeptides 772:794 tryptic N-glycopeptides 772:794 Vitronectin was purified with immunoprecipitation by monoclonal antibody from plasma and digested to tryptic N-glycopeptides. 25374123 5 2 used used 838:841 arg2 enrichment 802:811 enrichment 802:811 enrichment with HILIC materials 802:832 Then, enrichment with HILIC materials was used and followed by analysis with nano-LC/MS/MS. 25374123 3 3 theme tandem 542:547 arg1 spectrometry 554:565 tandem mass spectrometry 542:565 tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment 542:668 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 9 4 theme vitronectin 1352:1362 arg1 N-glycopeptides 1394:1408 12 N-glycopeptides 1391:1408 12 N-glycopeptides first reported 1391:1423 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 4 theme vitronectin 1352:1362 arg1 vitronectin 1352:1362 vitronectin 1352:1362 vitronectin in human plasma 1352:1378 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 4 theme vitronectin 1352:1362 arg1 sites 1343:1347 the three N-glycosylation sites 1317:1347 the three N-glycosylation sites 1317:1347 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 0 5 from analysis 9:16 arg1 vitronectin 54:64 vitronectin 54:64 vitronectin from human plasma 54:82 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 4 6 gly N-glycopeptides 780:794 arg2 N-glycopeptides 780:794 tryptic N-glycopeptides 772:794 tryptic N-glycopeptides 772:794 Vitronectin was purified with immunoprecipitation by monoclonal antibody from plasma and digested to tryptic N-glycopeptides. 25374123 3 7 theme mass 549:552 arg1 spectrometry 554:565 tandem mass spectrometry 542:565 tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment 542:668 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 10 8 theme human 1569:1573 arg1 plasma 1575:1580 HCC human plasma 1565:1580 HCC human plasma 1565:1580 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 5 9 theme HILIC 818:822 arg1 materials 824:832 HILIC materials 818:832 HILIC materials 818:832 Then, enrichment with HILIC materials was used and followed by analysis with nano-LC/MS/MS. 25374123 9 10 theme human 1367:1371 arg1 plasma 1373:1378 human plasma 1367:1378 human plasma 1367:1378 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 10 11 theme triantennary 1509:1520 arg1 forms 1522:1526 triantennary forms 1509:1526 triantennary forms 1509:1526 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 6 12 theme N-glycopeptides 905:919 arg1 sequences 892:900 The sequences 888:900 The sequences of N-glycopeptides 888:919 The sequences of N-glycopeptides were identified from the mass spectra by high-energy C-trap dissociation (HCD) and collision-induced dissociation (CID). 25374123 7 13 used used 1073:1076 arg2 ions 1063:1066 oxonium ions 1055:1066 oxonium ions 1055:1066 In HCD mode, oxonium ions were used for recognizing glycopeptides and y ions for sequencing the peptide backbone. 25374123 0 14 theme mass 94:97 arg1 spectrometry 99:110 tandem mass spectrometry 87:110 tandem mass spectrometry with immunoprecipitation 87:135 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 8 15 theme Y 1169:1169 arg1 ions 1171:1174 Y ions 1169:1174 Y ions 1169:1174 In CID mode, Y ions were used for characterizing their glycoforms. 25374123 3 16 theme hydrophilic 605:615 arg1 HILIC 652:656 HILIC 652:656 HILIC 652:656 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 3 16 theme hydrophilic 605:615 arg1 chromatography 636:649 hydrophilic interaction liquid chromatography 605:649 hydrophilic interaction liquid chromatography (HILIC) 605:657 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 7 17 theme HCD 1045:1047 arg1 mode 1049:1052 HCD mode 1045:1052 HCD mode 1045:1052 In HCD mode, oxonium ions were used for recognizing glycopeptides and y ions for sequencing the peptide backbone. 25374123 2 18 theme multifunctional 317:331 arg1 glycoprotein 333:344 a multifunctional glycoprotein 315:344 a multifunctional glycoprotein in the blood 315:357 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 2 18 theme multifunctional 317:331 arg1 related 398:404 related 398:404 related 398:404 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 2 18 theme multifunctional 317:331 arg1 Vitronectin 283:293 Vitronectin 283:293 Vitronectin 283:293 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 10 19 with glycopeptides 1492:1504 arg1 fucosylation 1539:1550 outer fucosylation 1533:1550 outer fucosylation 1533:1550 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 0 20 from vitronectin 54:64 arg1 analysis 9:16 In-depth analysis 0:16 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 0:136 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 2 21 from matrix 381:386 arg1 blood 353:357 the blood 349:357 the blood 349:357 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 10 22 theme forms 1522:1526 arg1 hybrid 1468:1473 three hybrid and four complex glycopeptides 1462:1504 hybrid 1468:1473 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 10 22 theme forms 1522:1526 arg1 glycopeptides 1492:1504 three hybrid and four complex glycopeptides 1462:1504 glycopeptides 1492:1504 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 9 23 gly N-glycopeptides 1264:1278 arg2 N-glycopeptides 1264:1278 17 site-specific N-glycopeptides 1247:1278 17 site-specific N-glycopeptides 1247:1278 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 1 24 from characterization 142:157 arg1 glycoprotein 198:209 glycoprotein 198:209 glycoprotein 198:209 The characterization of site-specific microheterogeneity in glycoprotein is very important for understanding cell biology and disease processes. 25374123 10 25 gly glycopeptides 1492:1504 arg2 glycopeptides 1492:1504 three hybrid and four complex glycopeptides 1462:1504 glycopeptides 1492:1504 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 10 25 gly glycopeptides 1492:1504 arg1 forms 1522:1526 triantennary forms 1509:1526 triantennary forms 1509:1526 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 4 26 from plasma 749:754 arg1 antibody 735:742 monoclonal antibody 724:742 monoclonal antibody from plasma 724:754 Vitronectin was purified with immunoprecipitation by monoclonal antibody from plasma and digested to tryptic N-glycopeptides. 25374123 0 27 from N-glycosylation 35:49 arg1 vitronectin 54:64 vitronectin 54:64 vitronectin from human plasma 54:82 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 0 27 from N-glycosylation 35:49 arg1 plasma 77:82 human plasma 71:82 human plasma 71:82 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 9 28 theme N-glycopeptides 1264:1278 arg1 result 1228:1233 a result 1226:1233 a result 1226:1233 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 28 theme N-glycopeptides 1264:1278 arg1 total 1238:1242 a total 1236:1242 a total of 17 site-specific N-glycopeptides 1236:1278 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 6 29 theme collision-induced 1004:1020 arg1 CID 1036:1038 CID 1036:1038 CID 1036:1038 The sequences of N-glycopeptides were identified from the mass spectra by high-energy C-trap dissociation (HCD) and collision-induced dissociation (CID). 25374123 6 29 theme collision-induced 1004:1020 arg1 dissociation 1022:1033 collision-induced dissociation 1004:1033 collision-induced dissociation (CID) 1004:1039 The sequences of N-glycopeptides were identified from the mass spectra by high-energy C-trap dissociation (HCD) and collision-induced dissociation (CID). 25374123 0 30 theme In-depth 0:7 arg1 analysis 9:16 In-depth analysis 0:16 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 0:136 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 10 31 theme outer 1533:1537 arg1 fucosylation 1539:1550 outer fucosylation 1533:1550 outer fucosylation 1533:1550 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 0 32 with spectrometry 99:110 arg1 immunoprecipitation 117:135 immunoprecipitation 117:135 immunoprecipitation 117:135 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 10 33 with hybrid 1468:1473 arg1 fucosylation 1539:1550 outer fucosylation 1533:1550 outer fucosylation 1533:1550 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 2 34 theme hepatocellular 409:422 arg1 HCC 435:437 HCC 435:437 HCC 435:437 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 2 34 theme hepatocellular 409:422 arg1 carcinoma 424:432 hepatocellular carcinoma 409:432 hepatocellular carcinoma (HCC) 409:438 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 0 35 theme site-specific 21:33 arg1 N-glycosylation 35:49 site-specific N-glycosylation 21:49 site-specific N-glycosylation in vitronectin from human plasma 21:82 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 3 36 theme interaction 617:627 arg1 HILIC 652:656 HILIC 652:656 HILIC 652:656 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 3 36 theme interaction 617:627 arg1 chromatography 636:649 hydrophilic interaction liquid chromatography 605:649 hydrophilic interaction liquid chromatography (HILIC) 605:657 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 5 37 with enrichment 802:811 arg1 materials 824:832 HILIC materials 818:832 HILIC materials 818:832 Then, enrichment with HILIC materials was used and followed by analysis with nano-LC/MS/MS. 25374123 9 38 gly N-glycopeptides 1394:1408 arg2 N-glycopeptides 1394:1408 12 N-glycopeptides 1391:1408 12 N-glycopeptides first reported 1391:1423 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 8 39 theme CID 1159:1161 arg1 mode 1163:1166 CID mode 1159:1166 CID mode 1159:1166 In CID mode, Y ions were used for characterizing their glycoforms. 25374123 6 40 theme C-trap 974:979 arg1 HCD 995:997 HCD 995:997 HCD 995:997 The sequences of N-glycopeptides were identified from the mass spectra by high-energy C-trap dissociation (HCD) and collision-induced dissociation (CID). 25374123 6 40 theme C-trap 974:979 arg1 dissociation 981:992 high-energy C-trap dissociation 962:992 high-energy C-trap dissociation (HCD) 962:998 The sequences of N-glycopeptides were identified from the mass spectra by high-energy C-trap dissociation (HCD) and collision-induced dissociation (CID). 25374123 3 41 theme liquid 629:634 arg1 HILIC 652:656 HILIC 652:656 HILIC 652:656 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 3 41 theme liquid 629:634 arg1 chromatography 636:649 hydrophilic interaction liquid chromatography 605:649 hydrophilic interaction liquid chromatography (HILIC) 605:657 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 1 42 theme cell 247:250 arg1 biology 252:258 cell biology 247:258 cell biology 247:258 The characterization of site-specific microheterogeneity in glycoprotein is very important for understanding cell biology and disease processes. 25374123 8 43 used used 1181:1184 arg2 ions 1171:1174 Y ions 1169:1174 Y ions 1169:1174 In CID mode, Y ions were used for characterizing their glycoforms. 25374123 7 44 theme peptide 1138:1144 arg1 backbone 1146:1153 the peptide backbone 1134:1153 the peptide backbone 1134:1153 In HCD mode, oxonium ions were used for recognizing glycopeptides and y ions for sequencing the peptide backbone. 25374123 6 45 theme high-energy 962:972 arg1 HCD 995:997 HCD 995:997 HCD 995:997 The sequences of N-glycopeptides were identified from the mass spectra by high-energy C-trap dissociation (HCD) and collision-induced dissociation (CID). 25374123 6 45 theme high-energy 962:972 arg1 dissociation 981:992 high-energy C-trap dissociation 962:992 high-energy C-trap dissociation (HCD) 962:998 The sequences of N-glycopeptides were identified from the mass spectra by high-energy C-trap dissociation (HCD) and collision-induced dissociation (CID). 25374123 10 46 gly fucosylation 1539:1550 arg1 hybrid 1468:1473 three hybrid and four complex glycopeptides 1462:1504 hybrid 1468:1473 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 10 46 gly fucosylation 1539:1550 arg1 glycopeptides 1492:1504 three hybrid and four complex glycopeptides 1462:1504 glycopeptides 1492:1504 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 3 47 theme site-specific 478:490 arg1 N-glycopeptides 492:506 the site-specific N-glycopeptides 474:506 the site-specific N-glycopeptides of vitronectin in human plasma 474:537 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 0 48 theme N-glycosylation 35:49 arg1 analysis 9:16 In-depth analysis 0:16 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 0:136 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 6 49 gly N-glycopeptides 905:919 arg2 N-glycopeptides 905:919 N-glycopeptides 905:919 N-glycopeptides 905:919 The sequences of N-glycopeptides were identified from the mass spectra by high-energy C-trap dissociation (HCD) and collision-induced dissociation (CID). 25374123 10 50 theme HCC 1565:1567 arg1 plasma 1575:1580 HCC human plasma 1565:1580 HCC human plasma 1565:1580 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 0 51 from plasma 77:82 arg1 vitronectin 54:64 vitronectin 54:64 vitronectin from human plasma 54:82 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 0 51 from plasma 77:82 arg1 N-glycosylation 35:49 site-specific N-glycosylation 21:49 site-specific N-glycosylation in vitronectin from human plasma 21:82 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 9 52 from plasma 1373:1378 arg1 N-glycopeptides 1394:1408 12 N-glycopeptides 1391:1408 12 N-glycopeptides first reported 1391:1423 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 52 from plasma 1373:1378 arg1 vitronectin 1352:1362 vitronectin 1352:1362 vitronectin in human plasma 1352:1378 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 52 from plasma 1373:1378 arg1 sites 1343:1347 the three N-glycosylation sites 1317:1347 the three N-glycosylation sites 1317:1347 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 4 53 theme monoclonal 724:733 arg1 antibody 735:742 monoclonal antibody 724:742 monoclonal antibody from plasma 724:754 Vitronectin was purified with immunoprecipitation by monoclonal antibody from plasma and digested to tryptic N-glycopeptides. 25374123 10 54 theme complex 1484:1490 arg1 glycopeptides 1492:1504 three hybrid and four complex glycopeptides 1462:1504 glycopeptides 1492:1504 Finally, we specifically found that three hybrid and four complex glycopeptides of triantennary forms with outer fucosylation increased in HCC human plasma. 25374123 9 55 from sites 1343:1347 arg1 plasma 1373:1378 human plasma 1367:1378 human plasma 1367:1378 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 3 56 gly N-glycopeptides 492:506 arg2 N-glycopeptides 492:506 the site-specific N-glycopeptides 474:506 the site-specific N-glycopeptides of vitronectin in human plasma 474:537 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 3 56 gly N-glycopeptides 492:506 arg1 vitronectin 511:521 vitronectin 511:521 vitronectin 511:521 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 3 57 from N-glycopeptides 492:506 arg1 plasma 532:537 human plasma 526:537 human plasma 526:537 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 3 58 theme vitronectin 511:521 arg1 N-glycopeptides 492:506 the site-specific N-glycopeptides 474:506 the site-specific N-glycopeptides of vitronectin in human plasma 474:537 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 9 59 from vitronectin 1352:1362 arg1 plasma 1373:1378 human plasma 1367:1378 human plasma 1367:1378 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 7 60 gly glycopeptides 1094:1106 arg2 glycopeptides 1094:1106 glycopeptides 1094:1106 glycopeptides 1094:1106 In HCD mode, oxonium ions were used for recognizing glycopeptides and y ions for sequencing the peptide backbone. 25374123 6 61 theme mass 946:949 arg1 spectra 951:957 the mass spectra 942:957 the mass spectra 942:957 The sequences of N-glycopeptides were identified from the mass spectra by high-energy C-trap dissociation (HCD) and collision-induced dissociation (CID). 25374123 3 62 dep immunoprecipitation 581:599 arg1 enrichment 659:668 enrichment 659:668 enrichment 659:668 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 1 63 gly glycoprotein 198:209 arg1 glycoprotein 198:209 glycoprotein 198:209 glycoprotein 198:209 The characterization of site-specific microheterogeneity in glycoprotein is very important for understanding cell biology and disease processes. 25374123 9 64 theme site-specific 1250:1262 arg1 N-glycopeptides 1264:1278 17 site-specific N-glycopeptides 1247:1278 17 site-specific N-glycopeptides 1247:1278 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 0 65 gly N-glycosylation 35:49 arg1 vitronectin 54:64 vitronectin 54:64 vitronectin from human plasma 54:82 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 7 66 theme oxonium 1055:1061 arg1 ions 1063:1066 oxonium ions 1055:1066 oxonium ions 1055:1066 In HCD mode, oxonium ions were used for recognizing glycopeptides and y ions for sequencing the peptide backbone. 25374123 2 67 theme extracellular 367:379 arg1 matrix 381:386 the extracellular matrix 363:386 the extracellular matrix 363:386 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 2 67 theme extracellular 367:379 arg1 related 398:404 related 398:404 related 398:404 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 1 68 theme disease 264:270 arg1 processes 272:280 disease processes 264:280 disease processes 264:280 The characterization of site-specific microheterogeneity in glycoprotein is very important for understanding cell biology and disease processes. 25374123 9 69 theme N-glycosylation 1327:1341 arg1 N-glycopeptides 1394:1408 12 N-glycopeptides 1391:1408 12 N-glycopeptides first reported 1391:1423 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 69 theme N-glycosylation 1327:1341 arg1 vitronectin 1352:1362 vitronectin 1352:1362 vitronectin in human plasma 1352:1378 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 69 theme N-glycosylation 1327:1341 arg1 sites 1343:1347 the three N-glycosylation sites 1317:1347 the three N-glycosylation sites 1317:1347 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 5 70 with analysis 859:866 arg1 nano-LC/MS/MS 873:885 nano-LC/MS/MS 873:885 nano-LC/MS/MS 873:885 Then, enrichment with HILIC materials was used and followed by analysis with nano-LC/MS/MS. 25374123 3 71 theme human 526:530 arg1 plasma 532:537 human plasma 526:537 human plasma 526:537 Here, we systematically analyzed the site-specific N-glycopeptides of vitronectin in human plasma by tandem mass spectrometry combined with immunoprecipitation and hydrophilic interaction liquid chromatography (HILIC) enrichment. 25374123 2 72 from glycoprotein 333:344 arg1 blood 353:357 the blood 349:357 the blood 349:357 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 9 73 gly N-glycosylation 1327:1341 arg2 three 1321:1325 three 1321:1325 three 1321:1325 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 73 gly N-glycosylation 1327:1341 arg2 sites 1343:1347 the three N-glycosylation sites 1317:1347 the three N-glycosylation sites 1317:1347 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 73 gly N-glycosylation 1327:1341 arg2 N-glycopeptides 1394:1408 12 N-glycopeptides 1391:1408 12 N-glycopeptides first reported 1391:1423 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 73 gly N-glycosylation 1327:1341 arg2 plasma 1373:1378 human plasma 1367:1378 human plasma 1367:1378 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 73 gly N-glycosylation 1327:1341 arg1 vitronectin 1352:1362 vitronectin 1352:1362 vitronectin in human plasma 1352:1378 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 9 73 gly N-glycosylation 1327:1341 arg2 vitronectin 1352:1362 vitronectin 1352:1362 vitronectin in human plasma 1352:1378 As a result, a total of 17 site-specific N-glycopeptides were completely identified in all of the three N-glycosylation sites of vitronectin in human plasma, including 12 N-glycopeptides first reported. 25374123 1 74 theme site-specific 162:174 arg1 microheterogeneity 176:193 site-specific microheterogeneity 162:193 site-specific microheterogeneity 162:193 The characterization of site-specific microheterogeneity in glycoprotein is very important for understanding cell biology and disease processes. 25374123 7 75 theme y 1112:1112 arg1 ions 1114:1117 y ions 1112:1117 y ions 1112:1117 In HCD mode, oxonium ions were used for recognizing glycopeptides and y ions for sequencing the peptide backbone. 25374123 0 76 theme human 71:75 arg1 plasma 77:82 human plasma 71:82 human plasma 71:82 In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. 25374123 1 77 theme microheterogeneity 176:193 arg1 characterization 142:157 The characterization 138:157 The characterization of site-specific microheterogeneity in glycoprotein 138:209 The characterization of site-specific microheterogeneity in glycoprotein is very important for understanding cell biology and disease processes. 25374123 1 77 theme microheterogeneity 176:193 arg1 important 219:227 important 219:227 important 219:227 The characterization of site-specific microheterogeneity in glycoprotein is very important for understanding cell biology and disease processes. 25374123 2 78 gly glycoprotein 333:344 arg1 glycoprotein 333:344 a multifunctional glycoprotein 315:344 a multifunctional glycoprotein in the blood 315:357 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 2 78 gly glycoprotein 333:344 arg1 related 398:404 related 398:404 related 398:404 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 25374123 2 78 gly glycoprotein 333:344 arg1 Vitronectin 283:293 Vitronectin 283:293 Vitronectin 283:293 Vitronectin is well known to be a multifunctional glycoprotein in the blood and the extracellular matrix, which is related to hepatocellular carcinoma (HCC). 22171320 10 0 from analysis 1698:1705 arg1 CID-MS 1642:1647 Subsequent CID-MS 1631:1647 Subsequent CID-MS(3) 1631:1650 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 10 0 from analysis 1698:1705 arg1 fragment-ions 1665:1677 selected fragment-ions 1656:1677 selected fragment-ions from the CID-MS(2) analysis 1656:1705 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 10 0 from analysis 1698:1705 arg1 3 1649:1649 3 1649:1649 3 1649:1649 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 10 1 theme selected 1656:1663 arg1 fragment-ions 1665:1677 selected fragment-ions 1656:1677 selected fragment-ions from the CID-MS(2) analysis 1656:1705 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 2 2 theme glycan 341:346 arg1 structures 348:357 glycan structures 341:357 glycan structures 341:357 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 7 3 theme fragmentation 1254:1266 arg1 techniques 1268:1277 collision induced dissociation (CID) and electron capture dissociation fragmentation techniques 1183:1277 collision induced dissociation (CID) and electron capture dissociation fragmentation techniques 1183:1277 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 6 4 theme solid 1003:1007 arg1 support 1009:1015 a solid support 1001:1015 a solid support 1001:1015 Sialylated urinary glycoproteins were conjugated to a solid support by hydrazide chemistry and trypsin digested. 22171320 10 5 theme CID-MS 1688:1693 arg1 analysis 1698:1705 the CID-MS(2) analysis 1684:1705 the CID-MS(2) analysis 1684:1705 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 7 6 theme capture 1233:1239 arg1 dissociation 1241:1252 electron capture dissociation 1224:1252 electron capture dissociation 1224:1252 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 0 7 theme Human 0:4 arg1 glycoproteomics 14:28 Human urinary glycoproteomics 0:28 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 0:113 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 22171320 9 8 theme tetra-antennary 1566:1580 arg1 N-glycans 1582:1590 tetra-antennary N-glycans 1566:1590 tetra-antennary N-glycans 1566:1590 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 4 9 theme MS-fragmentation 736:751 arg1 techniques 753:762 complementary MS-fragmentation techniques 722:762 complementary MS-fragmentation techniques for glycopeptide analysis 722:788 We have developed a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis. 22171320 14 10 theme intact 2264:2269 arg1 glycopeptides 2272:2284 "intact" glycopeptides 2263:2284 "intact" glycopeptides 2263:2284 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 11 11 theme peptide 1907:1913 arg1 sequences 1915:1923 peptide sequences 1907:1923 peptide sequences 1907:1923 In total, 58 N- and 63 O-linked glycopeptides from 53 glycoproteins were characterized with respect to glycan- and peptide sequences. 22171320 1 12 theme products 164:171 arg1 Urine 115:119 Urine 115:119 Urine 115:119 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 1 12 theme products 164:171 arg1 fluid 202:206 a challenging biological fluid 177:206 a challenging biological fluid for biomarker discovery 177:230 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 1 12 theme products 164:171 arg1 mixture 134:140 a complex mixture 124:140 a complex mixture of proteins and waste products 124:171 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 12 13 theme O-glycosylation 2083:2097 arg1 sites 2099:2103 40 of 57 putative O-glycosylation sites 2065:2103 40 of 57 putative O-glycosylation sites 2065:2103 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 9 14 theme core 1608:1611 arg1 O-glycans 1620:1628 fucosylated core 2-like O-glycans 1596:1628 fucosylated core 2-like O-glycans 1596:1628 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 4 15 theme urinary 681:687 arg1 glycoproteins/glycopeptides 689:715 urinary glycoproteins/glycopeptides 681:715 urinary glycoproteins/glycopeptides 681:715 We have developed a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis. 22171320 14 16 theme urinary 2235:2241 arg1 glycoproteins 2243:2255 human urinary glycoproteins 2229:2255 human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt 2229:2380 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 5 17 theme clinical 805:812 arg1 size 821:824 clinical sample size 805:824 clinical sample size 805:824 Starting from clinical sample size, we eliminated interfering urinary compounds by dialysis and concentrated the purified urinary proteins by lyophilization. 22171320 1 18 theme biological 191:200 arg1 fluid 202:206 a challenging biological fluid 177:206 a challenging biological fluid for biomarker discovery 177:230 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 4 19 gly glycopeptide 768:779 arg2 glycopeptide 768:779 glycopeptide analysis 768:788 glycopeptide analysis 768:788 We have developed a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis. 22171320 11 20 gly glycopeptides 1824:1836 arg2 glycopeptides 1824:1836 63 O-linked glycopeptides 1812:1836 63 O-linked glycopeptides 1812:1836 In total, 58 N- and 63 O-linked glycopeptides from 53 glycoproteins were characterized with respect to glycan- and peptide sequences. 22171320 11 20 gly glycopeptides 1824:1836 arg1 glycoproteins 1846:1858 53 glycoproteins 1843:1858 53 glycoproteins 1843:1858 In total, 58 N- and 63 O-linked glycopeptides from 53 glycoproteins were characterized with respect to glycan- and peptide sequences. 22171320 10 21 theme specific 1726:1733 arg1 b- 1735:1736 peptide specific b- 1718:1736 peptide specific b- 1718:1736 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 7 22 theme collision 1183:1191 arg1 dissociation 1201:1212 collision induced dissociation 1183:1212 collision induced dissociation (CID) 1183:1218 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 7 22 theme collision 1183:1191 arg1 CID 1215:1217 CID 1215:1217 CID 1215:1217 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 11 23 from glycoproteins 1846:1858 arg1 N- 1805:1806 58 N- 1802:1806 58 N- 1802:1806 In total, 58 N- and 63 O-linked glycopeptides from 53 glycoproteins were characterized with respect to glycan- and peptide sequences. 22171320 11 23 from glycoproteins 1846:1858 arg1 glycopeptides 1824:1836 63 O-linked glycopeptides 1812:1836 63 O-linked glycopeptides 1812:1836 In total, 58 N- and 63 O-linked glycopeptides from 53 glycoproteins were characterized with respect to glycan- and peptide sequences. 22171320 9 24 gly fucosylated 1596:1606 arg1 O-glycans 1620:1628 fucosylated core 2-like O-glycans 1596:1628 fucosylated core 2-like O-glycans 1596:1628 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 2 25 theme proteomic 242:250 arg1 studies 252:258 Previous proteomic studies 233:258 Previous proteomic studies 233:258 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 3 26 link O-linked 577:584 arg1 residues 587:594 asparagine (N-linked) or serine/threonine (O-linked) residues 534:594 residues 587:594 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 8 27 theme O-linked 1427:1434 arg1 structures 1448:1457 known N-linked biantennary complex-type and O-linked core 1-like structures 1383:1457 structures 1448:1457 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 5 28 theme interfering 841:851 arg1 compounds 861:869 interfering urinary compounds 841:869 interfering urinary compounds 841:869 Starting from clinical sample size, we eliminated interfering urinary compounds by dialysis and concentrated the purified urinary proteins by lyophilization. 22171320 7 29 theme mild 1107:1110 arg1 hydrolysis 1117:1126 mild acid hydrolysis 1107:1126 mild acid hydrolysis 1107:1126 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 1 30 theme complex 126:132 arg1 Urine 115:119 Urine 115:119 Urine 115:119 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 1 30 theme complex 126:132 arg1 mixture 134:140 a complex mixture 124:140 a complex mixture of proteins and waste products 124:171 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 10 31 from CID-MS 1642:1647 arg1 analysis 1698:1705 the CID-MS(2) analysis 1684:1705 the CID-MS(2) analysis 1684:1705 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 8 32 theme 1-like 1441:1446 arg1 structures 1448:1457 known N-linked biantennary complex-type and O-linked core 1-like structures 1383:1457 structures 1448:1457 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 12 33 theme Ser/Thr 2034:2040 arg1 s 2058:2058 Ser/Thr attachment site(s) 2034:2059 Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites 2034:2103 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 0 34 theme glycosylations 84:97 arg1 analysis 56:63 attachment site specific analysis 31:63 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 0:113 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 22171320 8 35 located observed 1355:1362 arg1 2 1290:1290 2 1290:1290 2 1290:1290 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 8 35 located observed 1355:1362 arg2 Hex 1294:1296 Hex(5) 1294:1299 Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr 1294:1338 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 8 35 located observed 1355:1362 arg1 agreement 1368:1376 agreement 1368:1376 agreement with known N-linked biantennary complex-type and O-linked core 1-like structures 1368:1457 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 8 35 located observed 1355:1362 arg1 CID-MS 1283:1288 CID-MS 1283:1288 CID-MS(2) 1283:1291 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 2 36 theme glycoproteins 394:406 arg1 structures 348:357 glycan structures 341:357 glycan structures 341:357 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 2 36 theme glycoproteins 394:406 arg1 sites 377:381 glycosylation sites 363:381 glycosylation sites 363:381 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 2 36 theme glycoproteins 394:406 arg1 glycoproteins 394:406 urinary glycoproteins 386:406 urinary glycoproteins 386:406 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 14 37 gly glycoproteins 2243:2255 arg1 glycoproteins 2243:2255 human urinary glycoproteins 2229:2255 human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt 2229:2380 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 5 38 theme purified 904:911 arg1 proteins 921:928 the purified urinary proteins 900:928 the purified urinary proteins 900:928 Starting from clinical sample size, we eliminated interfering urinary compounds by dialysis and concentrated the purified urinary proteins by lyophilization. 22171320 14 39 dep glycoproteins 2243:2255 arg1 studied 2291:2297 studied 2291:2297 studied 2291:2297 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 14 39 dep glycoproteins 2243:2255 arg1 proven 2361:2366 proven 2361:2366 were proven without doubt 2356:2380 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 3 40 theme complexity 486:495 arg1 difficult 461:469 difficult 461:469 difficult 461:469 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 12 41 theme dissociation 1970:1981 arg1 techniques 1983:1992 electron capture dissociation techniques 1953:1992 electron capture dissociation techniques 1953:1992 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 14 42 theme glycans 2321:2327 arg1 presence 2309:2316 the presence 2305:2316 the presence of glycans 2305:2327 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 10 43 theme Subsequent 1631:1640 arg1 CID-MS 1642:1647 Subsequent CID-MS 1631:1647 Subsequent CID-MS(3) 1631:1650 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 10 43 theme Subsequent 1631:1640 arg1 3 1649:1649 3 1649:1649 3 1649:1649 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 9 44 dep N-glycans 1582:1590 arg1 e.g. 1561:1564 e.g. 1561:1564 e.g. 1561:1564 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 6 45 gly glycoproteins 968:980 arg1 glycoproteins 968:980 Sialylated urinary glycoproteins 949:980 Sialylated urinary glycoproteins 949:980 Sialylated urinary glycoproteins were conjugated to a solid support by hydrazide chemistry and trypsin digested. 22171320 9 46 theme Additional 1474:1483 arg1 glycoforms 1485:1494 Additional glycoforms 1474:1494 Additional glycoforms for specific N- and O-linked glycopeptides 1474:1537 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 0 47 link O-linked 75:82 arg1 glycosylations 84:97 N- and O-linked glycosylations 68:97 N- and O-linked glycosylations 68:97 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 22171320 9 48 gly glycopeptides 1525:1537 arg2 glycopeptides 1525:1537 O-linked glycopeptides 1516:1537 O-linked glycopeptides 1516:1537 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 13 49 theme O-glycosylation 2120:2134 arg1 sites 2136:2140 29 O-glycosylation sites 2117:2140 29 O-glycosylation sites which have, to our knowledge, not been previously reported 2117:2199 We defined 29 O-glycosylation sites which have, to our knowledge, not been previously reported. 22171320 0 50 theme specific 47:54 arg1 analysis 56:63 attachment site specific analysis 31:63 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 0:113 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 22171320 12 51 theme CID 1945:1947 arg1 combination 1930:1940 The combination 1926:1940 The combination of CID and electron capture dissociation techniques 1926:1992 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 6 52 theme Sialylated 949:958 arg1 glycoproteins 968:980 Sialylated urinary glycoproteins 949:980 Sialylated urinary glycoproteins 949:980 Sialylated urinary glycoproteins were conjugated to a solid support by hydrazide chemistry and trypsin digested. 22171320 3 53 theme glycan 500:505 arg1 structures 507:516 glycan structures 500:516 glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues 500:594 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 12 54 theme electron 1953:1960 arg1 dissociation 1970:1981 electron capture dissociation 1953:1981 electron capture dissociation techniques 1953:1992 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 0 55 dep glycoproteomics 14:28 arg1 analysis 56:63 attachment site specific analysis 31:63 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 0:113 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 22171320 11 56 link O-linked 1815:1822 arg1 glycopeptides 1824:1836 63 O-linked glycopeptides 1812:1836 63 O-linked glycopeptides 1812:1836 In total, 58 N- and 63 O-linked glycopeptides from 53 glycoproteins were characterized with respect to glycan- and peptide sequences. 22171320 4 57 theme glycoproteomic 617:630 arg1 approach 632:639 a glycoproteomic approach 615:639 a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis 615:788 We have developed a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis. 22171320 2 58 theme glycosylation 363:375 arg1 sites 377:381 glycosylation sites 363:381 glycosylation sites 363:381 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 2 58 theme glycosylation 363:375 arg1 glycoproteins 394:406 urinary glycoproteins 386:406 urinary glycoproteins 386:406 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 9 59 theme O-linked 1516:1523 arg1 glycopeptides 1525:1537 O-linked glycopeptides 1516:1537 O-linked glycopeptides 1516:1537 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 14 60 theme " 2270:2270 arg1 glycopeptides 2272:2284 "intact" glycopeptides 2263:2284 "intact" glycopeptides 2263:2284 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 10 61 theme fragment-ions 1665:1677 arg1 CID-MS 1642:1647 Subsequent CID-MS 1631:1647 Subsequent CID-MS(3) 1631:1650 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 10 61 theme fragment-ions 1665:1677 arg1 3 1649:1649 3 1649:1649 3 1649:1649 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 5 62 theme urinary 853:859 arg1 compounds 861:869 interfering urinary compounds 841:869 interfering urinary compounds 841:869 Starting from clinical sample size, we eliminated interfering urinary compounds by dialysis and concentrated the purified urinary proteins by lyophilization. 22171320 4 63 gly glycoproteins/glycopeptides 689:715 arg2 glycoproteins/glycopeptides 689:715 urinary glycoproteins/glycopeptides 681:715 urinary glycoproteins/glycopeptides 681:715 We have developed a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis. 22171320 8 64 link N-linked 1389:1396 arg1 complex-type 1410:1421 complex-type 1410:1421 complex-type 1410:1421 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 7 65 theme dissociation 1241:1252 arg1 techniques 1268:1277 collision induced dissociation (CID) and electron capture dissociation fragmentation techniques 1183:1277 collision induced dissociation (CID) and electron capture dissociation fragmentation techniques 1183:1277 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 3 66 theme serine/threonine 559:574 arg1 residues 587:594 asparagine (N-linked) or serine/threonine (O-linked) residues 534:594 residues 587:594 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 7 67 gly glycopeptides 1075:1087 arg2 glycopeptides 1075:1087 Desialylated glycopeptides 1062:1087 Desialylated glycopeptides 1062:1087 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 8 68 with agreement 1368:1376 arg1 structures 1448:1457 known N-linked biantennary complex-type and O-linked core 1-like structures 1383:1457 structures 1448:1457 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 8 68 with agreement 1368:1376 arg1 complex-type 1410:1421 complex-type 1410:1421 complex-type 1410:1421 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 7 69 theme electron 1224:1231 arg1 dissociation 1241:1252 electron capture dissociation 1224:1252 electron capture dissociation 1224:1252 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 12 70 gly O-glycosylation 2083:2097 arg2 sites 2099:2103 40 of 57 putative O-glycosylation sites 2065:2103 40 of 57 putative O-glycosylation sites 2065:2103 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 12 70 gly O-glycosylation 2083:2097 arg2 57 2071:2072 57 2071:2072 57 2071:2072 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 1 71 theme proteins 145:152 arg1 Urine 115:119 Urine 115:119 Urine 115:119 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 1 71 theme proteins 145:152 arg1 fluid 202:206 a challenging biological fluid 177:206 a challenging biological fluid for biomarker discovery 177:230 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 1 71 theme proteins 145:152 arg1 mixture 134:140 a complex mixture 124:140 a complex mixture of proteins and waste products 124:171 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 8 72 link O-linked 1427:1434 arg1 structures 1448:1457 known N-linked biantennary complex-type and O-linked core 1-like structures 1383:1457 structures 1448:1457 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 9 73 link O-linked 1516:1523 arg1 glycopeptides 1525:1537 O-linked glycopeptides 1516:1537 O-linked glycopeptides 1516:1537 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 4 74 theme glycoproteins/glycopeptides 689:715 arg1 purification 665:676 efficient purification 655:676 efficient purification of urinary glycoproteins/glycopeptides 655:715 We have developed a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis. 22171320 10 75 theme peptide 1718:1724 arg1 b- 1735:1736 peptide specific b- 1718:1736 peptide specific b- 1718:1736 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 1 76 theme waste 158:162 arg1 products 164:171 waste products 158:171 waste products 158:171 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 4 77 theme complementary 722:734 arg1 techniques 753:762 complementary MS-fragmentation techniques 722:762 complementary MS-fragmentation techniques for glycopeptide analysis 722:788 We have developed a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis. 22171320 2 78 theme urinary 291:297 arg1 proteins 299:306 more than 2800 urinary proteins 276:306 more than 2800 urinary proteins 276:306 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 9 79 theme fucosylated 1596:1606 arg1 O-glycans 1620:1628 fucosylated core 2-like O-glycans 1596:1628 fucosylated core 2-like O-glycans 1596:1628 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 12 80 theme putative 2074:2081 arg1 sites 2099:2103 40 of 57 putative O-glycosylation sites 2065:2103 40 of 57 putative O-glycosylation sites 2065:2103 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 8 81 theme core 1436:1439 arg1 structures 1448:1457 known N-linked biantennary complex-type and O-linked core 1-like structures 1383:1457 structures 1448:1457 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 4 82 theme efficient 655:663 arg1 purification 665:676 efficient purification 655:676 efficient purification of urinary glycoproteins/glycopeptides 655:715 We have developed a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis. 22171320 14 83 theme glycoproteins 2243:2255 arg1 This 2202:2205 This 2202:2205 This 2202:2205 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 14 83 theme glycoproteins 2243:2255 arg1 study 2220:2224 the first study 2210:2224 the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt 2210:2380 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 7 84 theme induced 1193:1199 arg1 dissociation 1201:1212 collision induced dissociation 1183:1212 collision induced dissociation (CID) 1183:1218 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 7 84 theme induced 1193:1199 arg1 CID 1215:1217 CID 1215:1217 CID 1215:1217 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 9 85 theme 2-like 1613:1618 arg1 O-glycans 1620:1628 fucosylated core 2-like O-glycans 1596:1628 fucosylated core 2-like O-glycans 1596:1628 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 12 86 theme s 2058:2058 arg1 identification 2016:2029 the exact identification 2006:2029 the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites 2006:2103 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 3 87 link N-linked 546:553 arg1 asparagine 534:543 asparagine (N-linked) or serine/threonine (O-linked) residues 534:594 asparagine 534:543 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 14 88 theme human 2229:2233 arg1 glycoproteins 2243:2255 human urinary glycoproteins 2229:2255 human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt 2229:2380 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 14 89 theme first 2214:2218 arg1 This 2202:2205 This 2202:2205 This 2202:2205 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 14 89 theme first 2214:2218 arg1 study 2220:2224 the first study 2210:2224 the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt 2210:2380 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 7 90 theme tandem 1151:1156 arg1 experiments 1161:1171 tandem MS experiments 1151:1171 tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques 1151:1277 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 7 91 theme MS 1158:1159 arg1 experiments 1161:1171 tandem MS experiments 1151:1171 tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques 1151:1277 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 3 92 theme O-linked 577:584 arg1 residues 587:594 asparagine (N-linked) or serine/threonine (O-linked) residues 534:594 residues 587:594 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 0 93 theme N- 68:69 arg1 glycosylations 84:97 N- and O-linked glycosylations 68:97 N- and O-linked glycosylations 68:97 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 22171320 2 94 theme Previous 233:240 arg1 studies 252:258 Previous proteomic studies 233:258 Previous proteomic studies 233:258 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 3 95 located found 518:522 arg1 asparagine 534:543 asparagine (N-linked) or serine/threonine (O-linked) residues 534:594 asparagine 534:543 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 3 95 located found 518:522 arg1 residues 587:594 asparagine (N-linked) or serine/threonine (O-linked) residues 534:594 residues 587:594 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 3 95 located found 518:522 arg2 structures 507:516 glycan structures 500:516 glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues 500:594 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 0 96 theme O-linked 75:82 arg1 glycosylations 84:97 N- and O-linked glycosylations 68:97 N- and O-linked glycosylations 68:97 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 22171320 12 97 theme attachment 2042:2051 arg1 s 2058:2058 Ser/Thr attachment site(s) 2034:2059 Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites 2034:2103 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 7 98 theme acid 1112:1115 arg1 hydrolysis 1117:1126 mild acid hydrolysis 1107:1126 mild acid hydrolysis 1107:1126 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 8 99 dep Hex 1294:1296 arg1 HexNAc 1300:1305 HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr 1300:1338 HexNAc 1300:1305 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 8 99 dep Hex 1294:1296 arg1 HexHexNAc-O-Ser/Thr 1320:1338 HexHexNAc-O-Ser/Thr 1320:1338 HexHexNAc-O-Ser/Thr 1320:1338 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 4 100 theme glycopeptide 768:779 arg1 analysis 781:788 glycopeptide analysis 768:788 glycopeptide analysis 768:788 We have developed a glycoproteomic approach that combines efficient purification of urinary glycoproteins/glycopeptides with complementary MS-fragmentation techniques for glycopeptide analysis. 22171320 5 101 theme sample 814:819 arg1 size 821:824 clinical sample size 805:824 clinical sample size 805:824 Starting from clinical sample size, we eliminated interfering urinary compounds by dialysis and concentrated the purified urinary proteins by lyophilization. 22171320 12 102 theme exact 2010:2014 arg1 identification 2016:2029 the exact identification 2006:2029 the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites 2006:2103 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 14 103 dep presence 2309:2316 arg1 i.e. 2300:2303 i.e. 2300:2303 i.e. 2300:2303 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 2 104 gly glycoproteins 394:406 arg1 glycoproteins 394:406 urinary glycoproteins 386:406 urinary glycoproteins 386:406 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 2 105 theme urinary 386:392 arg1 glycoproteins 394:406 urinary glycoproteins 386:406 urinary glycoproteins 386:406 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 0 106 theme urinary 6:12 arg1 glycoproteomics 14:28 Human urinary glycoproteomics 0:28 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 0:113 Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. 22171320 7 107 theme Desialylated 1062:1073 arg1 glycopeptides 1075:1087 Desialylated glycopeptides 1062:1087 Desialylated glycopeptides 1062:1087 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 11 108 gly glycoproteins 1846:1858 arg1 glycoproteins 1846:1858 53 glycoproteins 1843:1858 53 glycoproteins 1843:1858 In total, 58 N- and 63 O-linked glycopeptides from 53 glycoproteins were characterized with respect to glycan- and peptide sequences. 22171320 14 109 theme attachment 2339:2348 arg1 sites 2350:2354 their attachment sites 2333:2354 their attachment sites 2333:2354 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 5 110 theme urinary 913:919 arg1 proteins 921:928 the purified urinary proteins 900:928 the purified urinary proteins 900:928 Starting from clinical sample size, we eliminated interfering urinary compounds by dialysis and concentrated the purified urinary proteins by lyophilization. 22171320 12 111 theme techniques 1983:1992 arg1 combination 1930:1940 The combination 1926:1940 The combination of CID and electron capture dissociation techniques 1926:1992 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 10 112 used used 1759:1762 arg2 y-ions 1742:1747 y-ions 1742:1747 y-ions 1742:1747 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 10 112 used used 1759:1762 arg2 b- 1735:1736 peptide specific b- 1718:1736 peptide specific b- 1718:1736 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 2 113 gly glycosylation 363:375 arg2 sites 377:381 glycosylation sites 363:381 glycosylation sites 363:381 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 2 113 gly glycosylation 363:375 arg1 glycoproteins 394:406 urinary glycoproteins 386:406 urinary glycoproteins 386:406 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 2 113 gly glycosylation 363:375 arg2 glycoproteins 394:406 urinary glycoproteins 386:406 urinary glycoproteins 386:406 Previous proteomic studies have identified more than 2800 urinary proteins but analyses aimed at unraveling glycan structures and glycosylation sites of urinary glycoproteins are lacking. 22171320 1 114 theme challenging 179:189 arg1 fluid 202:206 a challenging biological fluid 177:206 a challenging biological fluid for biomarker discovery 177:230 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 3 115 theme Glycoproteomic 421:434 arg1 characterization 436:451 Glycoproteomic characterization 421:451 Glycoproteomic characterization 421:451 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 1 116 theme biomarker 212:220 arg1 discovery 222:230 biomarker discovery 212:230 biomarker discovery 212:230 Urine is a complex mixture of proteins and waste products and a challenging biological fluid for biomarker discovery. 22171320 10 117 theme peptide 1768:1774 arg1 identification 1776:1789 peptide identification 1768:1789 peptide identification 1768:1789 Subsequent CID-MS(3), of selected fragment-ions from the CID-MS(2) analysis, generated peptide specific b- and y-ions that were used for peptide identification. 22171320 6 118 theme urinary 960:966 arg1 glycoproteins 968:980 Sialylated urinary glycoproteins 949:980 Sialylated urinary glycoproteins 949:980 Sialylated urinary glycoproteins were conjugated to a solid support by hydrazide chemistry and trypsin digested. 22171320 7 119 theme dissociation 1201:1212 arg1 techniques 1268:1277 collision induced dissociation (CID) and electron capture dissociation fragmentation techniques 1183:1277 collision induced dissociation (CID) and electron capture dissociation fragmentation techniques 1183:1277 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 8 120 dep HexNAc 1300:1305 arg1 -N-Asn 1309:1314 -N-Asn 1309:1314 -N-Asn 1309:1314 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 8 120 dep HexNAc 1300:1305 arg1 4 1307:1307 4 1307:1307 4 1307:1307 In CID-MS(2), Hex(5)HexNAc(4)-N-Asn and HexHexNAc-O-Ser/Thr were typically observed, in agreement with known N-linked biantennary complex-type and O-linked core 1-like structures, respectively. 22171320 11 121 theme O-linked 1815:1822 arg1 glycopeptides 1824:1836 63 O-linked glycopeptides 1812:1836 63 O-linked glycopeptides 1812:1836 In total, 58 N- and 63 O-linked glycopeptides from 53 glycoproteins were characterized with respect to glycan- and peptide sequences. 22171320 9 122 theme specific 1500:1507 arg1 N- 1509:1510 specific N- 1500:1510 specific N- 1500:1510 Additional glycoforms for specific N- and O-linked glycopeptides were also identified, e.g. tetra-antennary N-glycans and fucosylated core 2-like O-glycans. 22171320 12 123 theme capture 1962:1968 arg1 dissociation 1970:1981 electron capture dissociation 1953:1981 electron capture dissociation techniques 1953:1992 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 14 124 gly glycopeptides 2272:2284 arg2 glycopeptides 2272:2284 "intact" glycopeptides 2263:2284 "intact" glycopeptides 2263:2284 This is the first study of human urinary glycoproteins where "intact" glycopeptides were studied, i.e. the presence of glycans and their attachment sites were proven without doubt. 22171320 7 125 gly Desialylated 1062:1073 arg1 glycopeptides 1075:1087 Desialylated glycopeptides 1062:1087 Desialylated glycopeptides 1062:1087 Desialylated glycopeptides, released through mild acid hydrolysis, were characterized by tandem MS experiments utilizing collision induced dissociation (CID) and electron capture dissociation fragmentation techniques. 22171320 12 126 theme site 2053:2056 arg1 s 2058:2058 Ser/Thr attachment site(s) 2034:2059 Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites 2034:2103 The combination of CID and electron capture dissociation techniques allowed for the exact identification of Ser/Thr attachment site(s) for 40 of 57 putative O-glycosylation sites. 22171320 3 127 theme structures 507:516 arg1 complexity 486:495 the complexity 482:495 the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues 482:594 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 22171320 13 128 gly O-glycosylation 2120:2134 arg2 sites 2136:2140 29 O-glycosylation sites 2117:2140 29 O-glycosylation sites which have, to our knowledge, not been previously reported 2117:2199 We defined 29 O-glycosylation sites which have, to our knowledge, not been previously reported. 22171320 13 128 gly O-glycosylation 2120:2134 arg2 29 2117:2118 29 2117:2118 29 2117:2118 We defined 29 O-glycosylation sites which have, to our knowledge, not been previously reported. 22171320 3 129 theme N-linked 546:553 arg1 asparagine 534:543 asparagine (N-linked) or serine/threonine (O-linked) residues 534:594 asparagine 534:543 Glycoproteomic characterization remains difficult because of the complexity of glycan structures found mainly on asparagine (N-linked) or serine/threonine (O-linked) residues. 15955802 3 0 link N-linked 361:368 arg1 sites 384:388 five N-linked glycosylation sites 356:388 five N-linked glycosylation sites 356:388 The mu (heavy) chain of IgM has five N-linked glycosylation sites. 15955802 6 1 theme occupancy 709:717 arg1 occupancy 680:688 100% occupancy 675:688 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563 675:758 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 7 2 theme Mannan-binding 761:774 arg1 MBL 784:786 MBL 784:786 MBL 784:786 Mannan-binding lectin (MBL) is a member of the collectin family of proteins, which bind to oligomannose and GlcNAc-terminating structures. 15955802 7 2 theme Mannan-binding 761:774 arg1 lectin 776:781 Mannan-binding lectin 761:781 Mannan-binding lectin (MBL) 761:787 Mannan-binding lectin (MBL) is a member of the collectin family of proteins, which bind to oligomannose and GlcNAc-terminating structures. 15955802 7 2 theme Mannan-binding 761:774 arg1 member 794:799 a member 792:799 a member 792:799 Mannan-binding lectin (MBL) is a member of the collectin family of proteins, which bind to oligomannose and GlcNAc-terminating structures. 15955802 8 3 theme IgM 1050:1052 arg1 purification 1013:1024 partial purification 1005:1024 partial purification of mouse and also human IgM 1005:1052 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 6 4 contain contain 609:615 arg1 IgM 592:594 IgM 592:594 IgM 592:594 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 6 4 contain contain 609:615 arg2 GlcNAc2Man5-9 644:656 23.4% oligomannose glycans GlcNAc2Man5-9 617:656 23.4% oligomannose glycans GlcNAc2Man5-9 617:656 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 9 5 theme Human 1055:1059 arg1 glycoforms 1065:1074 Human IgM glycoforms 1055:1074 Human IgM glycoforms that bind to immobilized MBL 1055:1103 Human IgM glycoforms that bind to immobilized MBL were isolated; these accounted for only 20% of total serum IgM. 15955802 4 6 theme oligomannose 498:509 arg1 glycans 511:517 oligomannose glycans 498:517 oligomannose glycans 498:517 Asn-171, Asn-332, and Asn-395 are occupied by complex glycans, whereas Asn-402 and Asn-563 are occupied by oligomannose glycans. 15955802 11 7 theme J 1487:1487 arg1 chain 1489:1493 the J chain 1483:1493 the J chain 1483:1493 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 11 8 gly glycosylated 1315:1326 arg1 model 1328:1332 A glycosylated model 1313:1332 A glycosylated model of pentameric IgM 1313:1350 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 6 9 theme 17 705:706 arg1 % 707:707 % 707:707 % 707:707 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 5 10 theme human 541:545 arg1 IgM 558:560 human polyclonal IgM 541:560 human polyclonal IgM 541:560 The glycosylation of human polyclonal IgM from serum has been analyzed. 15955802 10 11 theme more 1283:1286 arg1 structures 1301:1310 8% more oligomannose structures 1280:1310 8% more oligomannose structures 1280:1310 Compared with total serum IgM, the MBL-binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more oligomannose structures. 15955802 4 12 used occupied 425:432 arg2 Asn-171 391:397 Asn-171 391:397 Asn-171 391:397 Asn-171, Asn-332, and Asn-395 are occupied by complex glycans, whereas Asn-402 and Asn-563 are occupied by oligomannose glycans. 15955802 4 12 used occupied 425:432 arg2 Asn-395 413:419 Asn-395 413:419 Asn-395 413:419 Asn-171, Asn-332, and Asn-395 are occupied by complex glycans, whereas Asn-402 and Asn-563 are occupied by oligomannose glycans. 15955802 4 12 used occupied 425:432 arg2 Asn-332 400:406 Asn-332 400:406 Asn-332 400:406 Asn-171, Asn-332, and Asn-395 are occupied by complex glycans, whereas Asn-402 and Asn-563 are occupied by oligomannose glycans. 15955802 10 13 theme MBL-binding 1204:1214 arg1 glycoforms 1216:1225 the MBL-binding glycoforms 1200:1225 the MBL-binding glycoforms 1200:1225 Compared with total serum IgM, the MBL-binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more oligomannose structures. 15955802 1 14 theme primary 159:165 arg1 response 174:181 the primary immune response 155:181 the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer 155:252 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 9 15 gly glycoforms 1065:1074 arg1 IgM 1061:1063 Human IgM glycoforms 1055:1074 Human IgM glycoforms that bind to immobilized MBL 1055:1103 Human IgM glycoforms that bind to immobilized MBL were isolated; these accounted for only 20% of total serum IgM. 15955802 5 16 theme IgM 558:560 arg1 glycosylation 524:536 The glycosylation 520:536 The glycosylation of human polyclonal IgM from serum 520:571 The glycosylation of human polyclonal IgM from serum has been analyzed. 15955802 9 17 theme IgM 1061:1063 arg1 glycoforms 1065:1074 Human IgM glycoforms 1055:1074 Human IgM glycoforms that bind to immobilized MBL 1055:1103 Human IgM glycoforms that bind to immobilized MBL were isolated; these accounted for only 20% of total serum IgM. 15955802 6 18 from Asn-563 752:758 arg1 Asn-402 693:699 Asn-402 693:699 Asn-402 693:699 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 6 18 from Asn-563 752:758 arg1 occupancy 680:688 100% occupancy 675:688 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563 675:758 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 6 18 from Asn-563 752:758 arg1 occupancy 709:717 17% occupancy 705:717 17% occupancy of the variably occupied site at Asn-563 705:758 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 1 19 gly glycoprotein 104:115 arg1 glycoprotein 104:115 The glycoprotein IgM 100:119 The glycoprotein IgM 100:119 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 6 20 gly occupancy 680:688 arg2 occupancy 709:717 17% occupancy 705:717 17% occupancy of the variably occupied site at Asn-563 705:758 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 6 20 gly occupancy 680:688 arg2 Asn-402 693:699 Asn-402 693:699 Asn-402 693:699 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 6 21 gly occupancy 709:717 arg2 site 744:747 the variably occupied site 722:747 the variably occupied site 722:747 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 7 22 theme GlcNAc-terminating 869:886 arg1 structures 888:897 GlcNAc-terminating structures 869:897 GlcNAc-terminating structures 869:897 Mannan-binding lectin (MBL) is a member of the collectin family of proteins, which bind to oligomannose and GlcNAc-terminating structures. 15955802 10 23 theme GlcNAc-terminating 1246:1263 arg1 structures 1265:1274 97% more GlcNAc-terminating structures 1237:1274 97% more GlcNAc-terminating structures 1237:1274 Compared with total serum IgM, the MBL-binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more oligomannose structures. 15955802 4 24 used occupied 486:493 arg2 Asn-563 474:480 Asn-563 474:480 Asn-563 474:480 Asn-171, Asn-332, and Asn-395 are occupied by complex glycans, whereas Asn-402 and Asn-563 are occupied by oligomannose glycans. 15955802 4 24 used occupied 486:493 arg2 Asn-402 462:468 Asn-402 462:468 Asn-402 462:468 Asn-171, Asn-332, and Asn-395 are occupied by complex glycans, whereas Asn-402 and Asn-563 are occupied by oligomannose glycans. 15955802 3 25 contain has 352:354 arg2 sites 384:388 five N-linked glycosylation sites 356:388 five N-linked glycosylation sites 356:388 The mu (heavy) chain of IgM has five N-linked glycosylation sites. 15955802 3 25 contain has 352:354 arg1 chain 339:343 The mu (heavy) chain 324:343 The mu (heavy) chain of IgM 324:350 The mu (heavy) chain of IgM has five N-linked glycosylation sites. 15955802 13 26 theme aggregated 1794:1803 arg1 IgM 1805:1807 aggregated IgM 1794:1807 aggregated IgM 1794:1807 Antigen-bound IgM pentamers therefore do not activate complement via the lectin pathway, but MBL might have a role in the clearance of aggregated IgM. 15955802 11 27 contain has 1417:1419 arg1 IgM 1413:1415 IgM 1413:1415 IgM 1413:1415 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 11 27 contain has 1417:1419 arg2 faces 1434:1438 two distinct faces 1421:1438 two distinct faces 1421:1438 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 9 28 theme serum 1158:1162 arg1 IgM 1164:1166 total serum IgM 1152:1166 total serum IgM 1152:1166 Human IgM glycoforms that bind to immobilized MBL were isolated; these accounted for only 20% of total serum IgM. 15955802 8 29 theme commercial 902:911 arg1 resin 937:941 A commercial affinity chromatography resin 900:941 A commercial affinity chromatography resin containing immobilized MBL 900:968 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 8 29 theme commercial 902:911 arg1 useful 994:999 useful 994:999 useful 994:999 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 10 30 theme more 1241:1244 arg1 structures 1265:1274 97% more GlcNAc-terminating structures 1237:1274 97% more GlcNAc-terminating structures 1237:1274 Compared with total serum IgM, the MBL-binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more oligomannose structures. 15955802 0 31 theme mannan-binding 77:90 arg1 lectin 92:97 mannan-binding lectin 77:97 mannan-binding lectin 77:97 Human serum IgM glycosylation: identification of glycoforms that can bind to mannan-binding lectin. 15955802 8 32 theme chromatography 922:935 arg1 resin 937:941 A commercial affinity chromatography resin 900:941 A commercial affinity chromatography resin containing immobilized MBL 900:968 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 8 32 theme chromatography 922:935 arg1 useful 994:999 useful 994:999 useful 994:999 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 13 33 theme lectin 1732:1737 arg1 pathway 1739:1745 the lectin pathway 1728:1745 the lectin pathway 1728:1745 Antigen-bound IgM pentamers therefore do not activate complement via the lectin pathway, but MBL might have a role in the clearance of aggregated IgM. 15955802 7 34 theme collectin 808:816 arg1 family 818:823 the collectin family 804:823 the collectin family of proteins 804:835 Mannan-binding lectin (MBL) is a member of the collectin family of proteins, which bind to oligomannose and GlcNAc-terminating structures. 15955802 8 35 contain containing 943:952 arg2 MBL 966:968 immobilized MBL 954:968 immobilized MBL 954:968 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 8 35 contain containing 943:952 arg1 resin 937:941 A commercial affinity chromatography resin 900:941 A commercial affinity chromatography resin containing immobilized MBL 900:968 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 8 35 contain containing 943:952 arg1 useful 994:999 useful 994:999 useful 994:999 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 0 36 theme Human 0:4 arg1 glycosylation 16:28 Human serum IgM glycosylation 0:28 Human serum IgM glycosylation 0:28 Human serum IgM glycosylation: identification of glycoforms that can bind to mannan-binding lectin. 15955802 1 37 theme a 244:244 arg1 hexamer 246:252 a pentamer and a hexamer 229:252 hexamer 246:252 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 11 38 theme pentameric 1337:1346 arg1 IgM 1348:1350 pentameric IgM 1337:1350 pentameric IgM 1337:1350 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 0 39 theme IgM 12:14 arg1 glycosylation 16:28 Human serum IgM glycosylation 0:28 Human serum IgM glycosylation 0:28 Human serum IgM glycosylation: identification of glycoforms that can bind to mannan-binding lectin. 15955802 13 40 contain have 1762:1765 arg1 MBL 1752:1754 MBL 1752:1754 MBL 1752:1754 Antigen-bound IgM pentamers therefore do not activate complement via the lectin pathway, but MBL might have a role in the clearance of aggregated IgM. 15955802 13 40 contain have 1762:1765 arg2 role 1769:1772 a role 1767:1772 a role 1767:1772 Antigen-bound IgM pentamers therefore do not activate complement via the lectin pathway, but MBL might have a role in the clearance of aggregated IgM. 15955802 11 41 theme non-antigen-binding 1513:1531 arg1 face 1533:1536 the non-antigen-binding face 1509:1536 the non-antigen-binding face 1509:1536 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 3 42 theme N-linked 361:368 arg1 sites 384:388 five N-linked glycosylation sites 356:388 five N-linked glycosylation sites 356:388 The mu (heavy) chain of IgM has five N-linked glycosylation sites. 15955802 4 43 dep occupied 425:432 arg1 whereas 454:460 whereas 454:460 whereas 454:460 Asn-171, Asn-332, and Asn-395 are occupied by complex glycans, whereas Asn-402 and Asn-563 are occupied by oligomannose glycans. 15955802 3 44 gly glycosylation 370:382 arg2 sites 384:388 five N-linked glycosylation sites 356:388 five N-linked glycosylation sites 356:388 The mu (heavy) chain of IgM has five N-linked glycosylation sites. 15955802 3 44 gly glycosylation 370:382 arg2 five 356:359 five 356:359 five 356:359 The mu (heavy) chain of IgM has five N-linked glycosylation sites. 15955802 10 45 contain contained 1227:1235 arg1 glycoforms 1216:1225 the MBL-binding glycoforms 1200:1225 the MBL-binding glycoforms 1200:1225 Compared with total serum IgM, the MBL-binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more oligomannose structures. 15955802 10 45 contain contained 1227:1235 arg2 structures 1265:1274 97% more GlcNAc-terminating structures 1237:1274 97% more GlcNAc-terminating structures 1237:1274 Compared with total serum IgM, the MBL-binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more oligomannose structures. 15955802 10 45 contain contained 1227:1235 arg2 structures 1301:1310 8% more oligomannose structures 1280:1310 8% more oligomannose structures 1280:1310 Compared with total serum IgM, the MBL-binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more oligomannose structures. 15955802 6 46 theme occupied 735:742 arg1 site 744:747 the variably occupied site 722:747 the variably occupied site 722:747 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 6 47 theme Asn-402 693:699 arg1 occupancy 680:688 100% occupancy 675:688 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563 675:758 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 10 48 theme serum 1189:1193 arg1 IgM 1195:1197 total serum IgM 1183:1197 total serum IgM 1183:1197 Compared with total serum IgM, the MBL-binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more oligomannose structures. 15955802 8 49 theme partial 1005:1011 arg1 purification 1013:1024 partial purification 1005:1024 partial purification of mouse and also human IgM 1005:1052 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 13 50 theme IgM 1805:1807 arg1 clearance 1781:1789 the clearance 1777:1789 the clearance of aggregated IgM 1777:1807 Antigen-bound IgM pentamers therefore do not activate complement via the lectin pathway, but MBL might have a role in the clearance of aggregated IgM. 15955802 6 51 with consistent 659:668 arg1 occupancy 680:688 100% occupancy 675:688 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563 675:758 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 6 52 theme glycans 636:642 arg1 GlcNAc2Man5-9 644:656 23.4% oligomannose glycans GlcNAc2Man5-9 617:656 23.4% oligomannose glycans GlcNAc2Man5-9 617:656 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 6 53 theme % 621:621 arg1 GlcNAc2Man5-9 644:656 23.4% oligomannose glycans GlcNAc2Man5-9 617:656 23.4% oligomannose glycans GlcNAc2Man5-9 617:656 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 6 54 theme % 707:707 arg1 occupancy 709:717 17% occupancy 705:717 17% occupancy of the variably occupied site at Asn-563 705:758 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 2 55 theme Pentameric 255:264 arg1 IgM 266:268 Pentameric IgM 255:268 Pentameric IgM 255:268 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 1 56 theme pentamer 231:238 arg1 hexamer 246:252 a pentamer and a hexamer 229:252 hexamer 246:252 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 8 57 theme human 1044:1048 arg1 IgM 1050:1052 human IgM 1044:1052 human IgM 1044:1052 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 2 58 from absent 301:306 arg1 hexamer 315:321 the hexamer 311:321 the hexamer 311:321 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 5 59 theme polyclonal 547:556 arg1 IgM 558:560 human polyclonal IgM 541:560 human polyclonal IgM 541:560 The glycosylation of human polyclonal IgM from serum has been analyzed. 15955802 9 60 theme immobilized 1089:1099 arg1 MBL 1101:1103 immobilized MBL 1089:1103 immobilized MBL 1089:1103 Human IgM glycoforms that bind to immobilized MBL were isolated; these accounted for only 20% of total serum IgM. 15955802 2 61 theme single 276:281 arg1 absent 301:306 absent 301:306 absent 301:306 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 2 61 theme single 276:281 arg1 chain 285:289 a single J chain 274:289 a single J chain 274:289 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 1 62 theme immune 167:172 arg1 response 174:181 the primary immune response 155:181 the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer 155:252 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 6 63 theme % 678:678 arg1 occupancy 680:688 100% occupancy 675:688 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563 675:758 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 1 64 dep serum 215:219 arg1 both 221:224 both 221:224 both 221:224 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 1 65 theme glycoprotein 104:115 arg1 antibody 134:141 the major antibody 124:141 the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer 124:252 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 1 65 theme glycoprotein 104:115 arg1 IgM 117:119 The glycoprotein IgM 100:119 The glycoprotein IgM 100:119 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 1 66 from antigens 186:193 arg1 serum 215:219 the serum 211:219 the serum 211:219 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 11 67 theme faces 1434:1438 arg1 faces 1434:1438 two distinct faces 1421:1438 two distinct faces 1421:1438 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 11 67 theme faces 1434:1438 arg1 one 1446:1448 one 1446:1448 one 1446:1448 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 11 68 theme IgM 1348:1350 arg1 model 1328:1332 A glycosylated model 1313:1332 A glycosylated model of pentameric IgM 1313:1350 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 1 69 theme major 128:132 arg1 antibody 134:141 the major antibody 124:141 the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer 124:252 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 1 69 theme major 128:132 arg1 IgM 117:119 The glycoprotein IgM 100:119 The glycoprotein IgM 100:119 The glycoprotein IgM is the major antibody produced in the primary immune response to antigens, circulating in the serum both as a pentamer and a hexamer. 15955802 12 70 theme Antigen-bound 1539:1551 arg1 IgM 1553:1555 Antigen-bound IgM 1539:1555 Antigen-bound IgM 1539:1555 Antigen-bound IgM does not bind to MBL, as the target glycans appear to become inaccessible once IgM has bound antigen. 15955802 9 71 theme total 1152:1156 arg1 IgM 1164:1166 total serum IgM 1152:1166 total serum IgM 1152:1166 Human IgM glycoforms that bind to immobilized MBL were isolated; these accounted for only 20% of total serum IgM. 15955802 8 72 theme affinity 913:920 arg1 resin 937:941 A commercial affinity chromatography resin 900:941 A commercial affinity chromatography resin containing immobilized MBL 900:968 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 8 72 theme affinity 913:920 arg1 useful 994:999 useful 994:999 useful 994:999 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 9 73 theme IgM 1164:1166 arg1 IgM 1164:1166 total serum IgM 1152:1166 total serum IgM 1152:1166 Human IgM glycoforms that bind to immobilized MBL were isolated; these accounted for only 20% of total serum IgM. 15955802 9 73 theme IgM 1164:1166 arg1 % 1147:1147 only 20% 1140:1147 only 20% of total serum IgM 1140:1166 Human IgM glycoforms that bind to immobilized MBL were isolated; these accounted for only 20% of total serum IgM. 15955802 10 74 theme oligomannose 1288:1299 arg1 structures 1301:1310 8% more oligomannose structures 1280:1310 8% more oligomannose structures 1280:1310 Compared with total serum IgM, the MBL-binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more oligomannose structures. 15955802 6 75 theme 23.4 617:620 arg1 % 621:621 % 621:621 % 621:621 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 13 76 theme Antigen-bound 1659:1671 arg1 pentamers 1677:1685 Antigen-bound IgM pentamers 1659:1685 Antigen-bound IgM pentamers 1659:1685 Antigen-bound IgM pentamers therefore do not activate complement via the lectin pathway, but MBL might have a role in the clearance of aggregated IgM. 15955802 8 77 theme immobilized 954:964 arg1 MBL 966:968 immobilized MBL 954:968 immobilized MBL 954:968 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 7 78 theme proteins 828:835 arg1 family 818:823 the collectin family 804:823 the collectin family of proteins 804:835 Mannan-binding lectin (MBL) is a member of the collectin family of proteins, which bind to oligomannose and GlcNAc-terminating structures. 15955802 0 79 theme serum 6:10 arg1 glycosylation 16:28 Human serum IgM glycosylation 0:28 Human serum IgM glycosylation 0:28 Human serum IgM glycosylation: identification of glycoforms that can bind to mannan-binding lectin. 15955802 7 80 theme family 818:823 arg1 lectin 776:781 Mannan-binding lectin 761:781 Mannan-binding lectin (MBL) 761:787 Mannan-binding lectin (MBL) is a member of the collectin family of proteins, which bind to oligomannose and GlcNAc-terminating structures. 15955802 7 80 theme family 818:823 arg1 member 794:799 a member 792:799 a member 792:799 Mannan-binding lectin (MBL) is a member of the collectin family of proteins, which bind to oligomannose and GlcNAc-terminating structures. 15955802 3 81 theme mu 328:329 arg1 chain 339:343 The mu (heavy) chain 324:343 The mu (heavy) chain of IgM 324:350 The mu (heavy) chain of IgM has five N-linked glycosylation sites. 15955802 10 82 theme total 1183:1187 arg1 IgM 1195:1197 total serum IgM 1183:1197 total serum IgM 1183:1197 Compared with total serum IgM, the MBL-binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more oligomannose structures. 15955802 3 83 theme IgM 348:350 arg1 chain 339:343 The mu (heavy) chain 324:343 The mu (heavy) chain of IgM 324:350 The mu (heavy) chain of IgM has five N-linked glycosylation sites. 15955802 6 84 from occupancy 680:688 arg1 Asn-563 752:758 Asn-563 752:758 Asn-563 752:758 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 11 85 theme glycosylated 1315:1326 arg1 model 1328:1332 A glycosylated model 1313:1332 A glycosylated model of pentameric IgM 1313:1350 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 13 86 theme IgM 1673:1675 arg1 pentamers 1677:1685 Antigen-bound IgM pentamers 1659:1685 Antigen-bound IgM pentamers 1659:1685 Antigen-bound IgM pentamers therefore do not activate complement via the lectin pathway, but MBL might have a role in the clearance of aggregated IgM. 15955802 4 87 theme complex 437:443 arg1 glycans 445:451 complex glycans 437:451 complex glycans 437:451 Asn-171, Asn-332, and Asn-395 are occupied by complex glycans, whereas Asn-402 and Asn-563 are occupied by oligomannose glycans. 15955802 6 88 theme 100 675:677 arg1 % 678:678 % 678:678 % 678:678 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 3 89 theme glycosylation 370:382 arg1 sites 384:388 five N-linked glycosylation sites 356:388 five N-linked glycosylation sites 356:388 The mu (heavy) chain of IgM has five N-linked glycosylation sites. 15955802 0 90 theme glycoforms 49:58 arg1 identification 31:44 identification 31:44 identification of glycoforms that can bind to mannan-binding lectin 31:97 Human serum IgM glycosylation: identification of glycoforms that can bind to mannan-binding lectin. 15955802 2 91 contain has 270:272 arg2 absent 301:306 absent 301:306 absent 301:306 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 2 91 contain has 270:272 arg2 chain 285:289 a single J chain 274:289 a single J chain 274:289 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 2 91 contain has 270:272 arg1 IgM 266:268 Pentameric IgM 255:268 Pentameric IgM 255:268 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 6 92 theme site 744:747 arg1 Asn-402 693:699 Asn-402 693:699 Asn-402 693:699 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 6 92 theme site 744:747 arg1 occupancy 709:717 17% occupancy 705:717 17% occupancy of the variably occupied site at Asn-563 705:758 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 15955802 0 93 dep identification 31:44 arg1 glycosylation 16:28 Human serum IgM glycosylation 0:28 Human serum IgM glycosylation 0:28 Human serum IgM glycosylation: identification of glycoforms that can bind to mannan-binding lectin. 15955802 2 94 from hexamer 315:321 arg1 absent 301:306 absent 301:306 absent 301:306 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 2 94 from hexamer 315:321 arg1 chain 285:289 a single J chain 274:289 a single J chain 274:289 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 3 95 theme heavy 332:336 arg1 chain 339:343 The mu (heavy) chain 324:343 The mu (heavy) chain of IgM 324:350 The mu (heavy) chain of IgM has five N-linked glycosylation sites. 15955802 11 96 theme distinct 1425:1432 arg1 faces 1434:1438 two distinct faces 1421:1438 two distinct faces 1421:1438 A glycosylated model of pentameric IgM was constructed, and from this model, it became evident that IgM has two distinct faces, only one of which can bind to antigen, as the J chain projects from the non-antigen-binding face. 15955802 5 97 from serum 567:571 arg1 glycosylation 524:536 The glycosylation 520:536 The glycosylation of human polyclonal IgM from serum 520:571 The glycosylation of human polyclonal IgM from serum has been analyzed. 15955802 2 98 theme J 283:283 arg1 absent 301:306 absent 301:306 absent 301:306 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 2 98 theme J 283:283 arg1 chain 285:289 a single J chain 274:289 a single J chain 274:289 Pentameric IgM has a single J chain, which is absent in the hexamer. 15955802 8 99 theme mouse 1029:1033 arg1 purification 1013:1024 partial purification 1005:1024 partial purification of mouse and also human IgM 1005:1052 A commercial affinity chromatography resin containing immobilized MBL has been reported to be useful for partial purification of mouse and also human IgM. 15955802 12 100 theme target 1586:1591 arg1 glycans 1593:1599 the target glycans 1582:1599 the target glycans 1582:1599 Antigen-bound IgM does not bind to MBL, as the target glycans appear to become inaccessible once IgM has bound antigen. 15955802 5 101 gly glycosylation 524:536 arg1 IgM 558:560 human polyclonal IgM 541:560 human polyclonal IgM 541:560 The glycosylation of human polyclonal IgM from serum has been analyzed. 15955802 6 102 theme oligomannose 623:634 arg1 GlcNAc2Man5-9 644:656 23.4% oligomannose glycans GlcNAc2Man5-9 617:656 23.4% oligomannose glycans GlcNAc2Man5-9 617:656 IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9, consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably occupied site at Asn-563. 20030399 8 0 link N-linked 1443:1450 arg1 IgA2 1435:1438 IgA2 1435:1438 IgA2 (4 N-linked sites) 1435:1457 The application of this tool to characterize the N- and O-linked glycopeptides from human secretory IgA (sIgA), consisting of secretory component (7 N-linked sites), IgA1 (2 N-linked, 4)GlcNAc beta (1-->.) 8130392 9 0 theme oligosaccharides 1532:1547 arg1 many 1509:1512 many 1509:1512 many 1509:1512 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 12 1 theme latter 1765:1770 arg1 trisaccharide 1772:1784 the latter trisaccharide 1761:1784 the latter trisaccharide 1761:1784 Since the latter trisaccharide was first [Yan, S.B., Chao, B.Y. and Van Halbeek,H. (1992) J. Cell. 8130392 12 1 theme latter 1765:1770 arg1 [Yan 1796:1799 [Yan 1796:1799 [Yan 1796:1799 Since the latter trisaccharide was first [Yan, S.B., Chao, B.Y. and Van Halbeek,H. (1992) J. Cell. 8130392 11 2 theme GalNAc 1696:1701 arg1 1-->4 1709:1713 1-->4 1709:1713 1-->4 1709:1713 , and/or in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 11 2 theme GalNAc 1696:1701 arg1 beta 1703:1706 GalNAc beta 1696:1706 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 1696:1752 , and/or in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 0 3 theme Novel 0:4 arg1 oligosaccharides 17:32 Novel Asn-linked oligosaccharides 0:32 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 0:105 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 1 4 theme recombinant 122:132 arg1 C 148:148 recombinant human protein C 122:148 recombinant human protein C expressed in human kidney 293 cells 122:184 are present in recombinant human protein C expressed in human kidney 293 cells. 8130392 4 5 theme Protein 576:582 arg1 C 584:584 Protein C 576:584 Protein C 576:584 Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. 8130392 4 5 theme Protein 576:582 arg1 protease 636:643 a heavily post-translationally modified serine protease 589:643 a heavily post-translationally modified serine protease with four N-glycosylation sites 589:675 Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. 8130392 7 6 theme Asn-linked 986:995 arg1 oligosaccharides 997:1012 The Asn-linked oligosaccharides 982:1012 The Asn-linked oligosaccharides of rHPC 982:1020 The Asn-linked oligosaccharides of rHPC were released by N-glycanase and separated into 25 fractions by high-pH anion-exchange chromatography. 8130392 2 7 theme human 236:240 arg1 cells 253:257 human kidney 293 cells 236:257 human kidney 293 cells 236:257 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 1 8 theme protein 140:146 arg1 C 148:148 recombinant human protein C 122:148 recombinant human protein C expressed in human kidney 293 cells 122:184 are present in recombinant human protein C expressed in human kidney 293 cells. 8130392 9 9 theme GalNAc 1584:1589 arg1 1-->4 1597:1601 1-->4 1597:1601 1-->4 1597:1601 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 9 theme GalNAc 1584:1589 arg1 beta 1591:1594 GalNAc beta 1584:1594 GalNAc beta (1-->4)GlcNAc beta (1-->.) 1584:1621 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 0 10 theme GlcNAc 87:92 arg1 beta 94:97 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta 49:97 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 49:105 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 8 11 theme abundant 1134:1141 arg1 oligosaccharides 1143:1158 The most abundant oligosaccharides 1125:1158 The most abundant oligosaccharides 1125:1158 The most abundant oligosaccharides were structurally characterized by glycosyl composition and linkage analysis, in conjunction with 1H-NMR spectroscopy at 600 MHz. 8130392 3 12 theme antithrombotic 508:521 arg1 drug 523:526 the recombinant antithrombotic drug 492:526 the recombinant antithrombotic drug 492:526 In seeking to elucidate the molecular basis for the improved efficacy of the recombinant antithrombotic drug, we focused on the carbohydrate moiety of rHPC. 8130392 5 13 theme lower 769:773 arg1 content 787:793 a 2-fold lower sialic acid content 760:793 a 2-fold lower sialic acid content 760:793 Glycosyl composition analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC. 8130392 4 14 theme modified 620:627 arg1 C 584:584 Protein C 576:584 Protein C 576:584 Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. 8130392 4 14 theme modified 620:627 arg1 protease 636:643 a heavily post-translationally modified serine protease 589:643 a heavily post-translationally modified serine protease with four N-glycosylation sites 589:675 Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. 8130392 10 15 theme 2-->6 1640:1644 arg1 1-->4 1659:1663 1-->4 1659:1663 1-->4 1659:1663 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 10 15 theme 2-->6 1640:1644 arg1 beta 1653:1656 NeuAc alpha (2-->6)GalNAc beta 1627:1656 NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta 1627:1675 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 1 16 from C 148:148 arg1 present 111:117 present 111:117 present 111:117 are present in recombinant human protein C expressed in human kidney 293 cells. 8130392 9 17 theme sialylated 1418:1427 arg1 oligosaccharides 1429:1444 the sialylated oligosaccharides 1414:1444 the sialylated oligosaccharides in rHPC are 1414:1456 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 6 18 link Asn-linked 915:924 arg1 oligosaccharides 926:941 its Asn-linked oligosaccharides 911:941 its Asn-linked oligosaccharides 911:941 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 5 19 theme Glycosyl 678:685 arg1 analysis 699:706 Glycosyl composition analysis 678:706 Glycosyl composition analysis of rHPC 678:714 Glycosyl composition analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC. 8130392 2 20 theme Recombinant 187:197 arg1 rHPC 216:219 rHPC 216:219 rHPC 216:219 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 2 20 theme Recombinant 187:197 arg1 C 213:213 Recombinant human Protein C 187:213 Recombinant human Protein C (rHPC) 187:220 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 5 21 theme plasma 807:812 arg1 HPC 814:816 plasma HPC 807:816 plasma HPC 807:816 Glycosyl composition analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC. 8130392 14 22 dep determinant 2079:2089 arg1 trisaccharide 2054:2066 terminal trisaccharide 2045:2066 terminal trisaccharide 2045:2066 terminal trisaccharide the PC-293 determinant. 8130392 13 23 theme Asn-linked 1890:1899 arg1 oligosaccharides 1901:1916 the Asn-linked oligosaccharides 1886:1916 the Asn-linked oligosaccharides of rHPC 1886:1924 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 0 24 theme [Fuc 68:71 arg1 beta 94:97 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta 49:97 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 49:105 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 2 25 theme Protein 205:211 arg1 rHPC 216:219 rHPC 216:219 rHPC 216:219 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 2 25 theme Protein 205:211 arg1 C 213:213 Recombinant human Protein C 187:213 Recombinant human Protein C (rHPC) 187:220 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 9 26 from rHPC 1449:1452 arg1 [formula 1483:1490 [formula 1483:1490 [formula: see text] 1483:1501 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 26 from rHPC 1449:1452 arg1 structure 1294:1302 The structure 1290:1302 The structure of the major neutral oligosaccharide in rHPC 1290:1347 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 26 from rHPC 1449:1452 arg1 representatives 1395:1409 Two representatives 1391:1409 : [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] 1369:1501 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 26 from rHPC 1449:1452 arg1 [formula 1459:1466 [formula 1459:1466 [formula: see text] 1459:1477 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 6 27 theme GalNAc/mol 891:900 arg1 rHPC 902:905 2.6 mol GalNAc/mol rHPC 883:905 2.6 mol GalNAc/mol rHPC 883:905 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 6 27 theme GalNAc/mol 891:900 arg1 N-acetylgalactosamine 860:880 N-acetylgalactosamine 860:880 N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides 860:941 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 9 28 from structure 1294:1302 arg1 rHPC 1344:1347 rHPC 1344:1347 rHPC 1344:1347 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 15 29 theme anticoagulant 2160:2172 arg1 activity 2174:2181 the higher anticoagulant activity 2149:2181 the higher anticoagulant activity of rHPC 2149:2189 The PC-293-containing oligosaccharides may contribute to the higher anticoagulant activity of rHPC as compared to plasma HPC. 8130392 6 30 theme GalNAc 974:979 arg1 devoid 964:969 devoid 964:969 devoid 964:969 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 2 31 theme plasma 301:306 arg1 HPC 308:310 plasma HPC 301:310 plasma HPC 301:310 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 5 32 theme higher 734:739 arg1 content 748:754 a 5-fold higher fucose content 725:754 a 5-fold higher fucose content 725:754 Glycosyl composition analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC. 8130392 8 33 with conjunction 1241:1251 arg1 spectroscopy 1265:1276 1H-NMR spectroscopy 1258:1276 1H-NMR spectroscopy at 600 MHz 1258:1287 The most abundant oligosaccharides were structurally characterized by glycosyl composition and linkage analysis, in conjunction with 1H-NMR spectroscopy at 600 MHz. 8130392 2 34 theme human 199:203 arg1 rHPC 216:219 rHPC 216:219 rHPC 216:219 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 2 34 theme human 199:203 arg1 C 213:213 Recombinant human Protein C 187:213 Recombinant human Protein C (rHPC) 187:220 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 9 35 dep rHPC 1449:1452 arg1 are 1454:1456 are 1454:1456 are 1454:1456 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 11 36 theme alpha 1720:1724 arg1 beta 1741:1744 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1696:1744 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 1696:1752 , and/or in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 15 37 theme PC-293-containing 2096:2112 arg1 oligosaccharides 2114:2129 The PC-293-containing oligosaccharides 2092:2129 The PC-293-containing oligosaccharides 2092:2129 The PC-293-containing oligosaccharides may contribute to the higher anticoagulant activity of rHPC as compared to plasma HPC. 8130392 13 38 theme rHPC 1921:1924 arg1 oligosaccharides 1901:1916 the Asn-linked oligosaccharides 1886:1916 the Asn-linked oligosaccharides of rHPC 1886:1924 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 39 theme 1-->4 2000:2004 arg1 1-->3 2018:2022 1-->3 2018:2022 1-->3 2018:2022 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 39 theme 1-->4 2000:2004 arg1 beta 2032:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1983:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1--> 1983:2041 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 7 40 theme high-pH 1086:1092 arg1 chromatography 1109:1122 high-pH anion-exchange chromatography 1086:1122 high-pH anion-exchange chromatography 1086:1122 The Asn-linked oligosaccharides of rHPC were released by N-glycanase and separated into 25 fractions by high-pH anion-exchange chromatography. 8130392 9 41 dep see 1381:1383 arg1 [formula 1371:1378 [formula 1371:1378 [formula 1371:1378 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 5 42 theme rHPC 711:714 arg1 analysis 699:706 Glycosyl composition analysis 678:706 Glycosyl composition analysis of rHPC 678:714 Glycosyl composition analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC. 8130392 9 43 from representatives 1395:1409 arg1 rHPC 1449:1452 rHPC are 1449:1456 rHPC are 1449:1456 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 12 44 dep [Yan 1796:1799 arg1 H 1835:1835 H 1835:1835 H 1835:1835 Since the latter trisaccharide was first [Yan, S.B., Chao, B.Y. and Van Halbeek,H. (1992) J. Cell. 8130392 12 44 dep [Yan 1796:1799 arg1 B.Y. 1814:1817 B.Y. 1814:1817 B.Y. 1814:1817 Since the latter trisaccharide was first [Yan, S.B., Chao, B.Y. and Van Halbeek,H. (1992) J. Cell. 8130392 12 44 dep [Yan 1796:1799 arg1 Halbeek 1827:1833 Halbeek 1827:1833 Halbeek 1827:1833 Since the latter trisaccharide was first [Yan, S.B., Chao, B.Y. and Van Halbeek,H. (1992) J. Cell. 8130392 12 44 dep [Yan 1796:1799 arg1 Chao 1808:1811 Chao 1808:1811 Chao 1808:1811 Since the latter trisaccharide was first [Yan, S.B., Chao, B.Y. and Van Halbeek,H. (1992) J. Cell. 8130392 12 44 dep [Yan 1796:1799 arg1 1992 1839:1842 1992 1839:1842 1992 1839:1842 Since the latter trisaccharide was first [Yan, S.B., Chao, B.Y. and Van Halbeek,H. (1992) J. Cell. 8130392 13 45 link Asn-linked 1890:1899 arg1 oligosaccharides 1901:1916 the Asn-linked oligosaccharides 1886:1916 the Asn-linked oligosaccharides of rHPC 1886:1924 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 0 46 theme beta 56:59 arg1 beta 94:97 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta 49:97 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 49:105 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 9 47 theme major 1311:1315 arg1 oligosaccharide 1325:1339 the major neutral oligosaccharide 1307:1339 the major neutral oligosaccharide in rHPC 1307:1347 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 48 dep representatives 1395:1409 arg1 see 1381:1383 see 1381:1383 see text 1381:1388 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 48 dep representatives 1395:1409 arg1 [formula 1483:1490 [formula 1483:1490 [formula: see text] 1483:1501 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 48 dep representatives 1395:1409 arg1 representatives 1395:1409 Two representatives 1391:1409 : [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] 1369:1501 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 48 dep representatives 1395:1409 arg1 [formula 1459:1466 [formula 1459:1466 [formula: see text] 1459:1477 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 14 49 theme terminal 2045:2052 arg1 trisaccharide 2054:2066 terminal trisaccharide 2045:2066 terminal trisaccharide 2045:2066 terminal trisaccharide the PC-293 determinant. 8130392 9 50 theme oligosaccharide 1325:1339 arg1 structure 1294:1302 The structure 1290:1302 The structure of the major neutral oligosaccharide in rHPC 1290:1347 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 50 theme oligosaccharide 1325:1339 arg1 representatives 1395:1409 Two representatives 1391:1409 : [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] 1369:1501 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 13 51 theme alpha 2011:2015 arg1 1-->3 2018:2022 1-->3 2018:2022 1-->3 2018:2022 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 51 theme alpha 2011:2015 arg1 beta 2032:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1983:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1--> 1983:2041 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 52 theme human 1939:1943 arg1 cells 1956:1960 human kidney 293 cells 1939:1960 human kidney 293 cells 1939:1960 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 3 53 theme rHPC 570:573 arg1 moiety 560:565 the carbohydrate moiety 543:565 the carbohydrate moiety of rHPC 543:573 In seeking to elucidate the molecular basis for the improved efficacy of the recombinant antithrombotic drug, we focused on the carbohydrate moiety of rHPC. 8130392 8 54 from MHz 1285:1287 arg1 spectroscopy 1265:1276 1H-NMR spectroscopy 1258:1276 1H-NMR spectroscopy at 600 MHz 1258:1287 The most abundant oligosaccharides were structurally characterized by glycosyl composition and linkage analysis, in conjunction with 1H-NMR spectroscopy at 600 MHz. 8130392 9 55 theme Asn-linked 1521:1530 arg1 oligosaccharides 1532:1547 the Asn-linked oligosaccharides 1517:1547 the Asn-linked oligosaccharides in rHPC 1517:1555 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 5 56 theme composition 687:697 arg1 analysis 699:706 Glycosyl composition analysis 678:706 Glycosyl composition analysis of rHPC 678:714 Glycosyl composition analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC. 8130392 2 57 theme higher 266:271 arg1 activity 287:294 a higher anticoagulant activity 264:294 a higher anticoagulant activity than plasma HPC 264:310 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 7 58 theme rHPC 1017:1020 arg1 oligosaccharides 997:1012 The Asn-linked oligosaccharides 982:1012 The Asn-linked oligosaccharides of rHPC 982:1020 The Asn-linked oligosaccharides of rHPC were released by N-glycanase and separated into 25 fractions by high-pH anion-exchange chromatography. 8130392 3 59 theme molecular 447:455 arg1 basis 457:461 the molecular basis 443:461 the molecular basis for the improved efficacy of the recombinant antithrombotic drug 443:526 In seeking to elucidate the molecular basis for the improved efficacy of the recombinant antithrombotic drug, we focused on the carbohydrate moiety of rHPC. 8130392 15 60 theme plasma 2206:2211 arg1 HPC 2213:2215 plasma HPC 2206:2215 plasma HPC 2206:2215 The PC-293-containing oligosaccharides may contribute to the higher anticoagulant activity of rHPC as compared to plasma HPC. 8130392 2 61 theme kidney 242:247 arg1 cells 253:257 human kidney 293 cells 236:257 human kidney 293 cells 236:257 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 0 62 link Asn-linked 6:15 arg1 oligosaccharides 17:32 Novel Asn-linked oligosaccharides 0:32 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 0:105 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 63 theme kidney 1945:1950 arg1 cells 1956:1960 human kidney 293 cells 1939:1960 human kidney 293 cells 1939:1960 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 10 64 dep 1--> 1678:1681 arg1 beta 1672:1675 NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta 1627:1675 NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta 1627:1675 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 5 65 theme acid 782:785 arg1 content 787:793 a 2-fold lower sialic acid content 760:793 a 2-fold lower sialic acid content 760:793 Glycosyl composition analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC. 8130392 8 66 theme glycosyl 1195:1202 arg1 composition 1204:1214 glycosyl composition 1195:1214 glycosyl composition 1195:1214 The most abundant oligosaccharides were structurally characterized by glycosyl composition and linkage analysis, in conjunction with 1H-NMR spectroscopy at 600 MHz. 8130392 5 67 theme sialic 775:780 arg1 content 787:793 a 2-fold lower sialic acid content 760:793 a 2-fold lower sialic acid content 760:793 Glycosyl composition analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC. 8130392 9 68 from oligosaccharides 1429:1444 arg1 rHPC 1449:1452 rHPC are 1449:1456 rHPC are 1449:1456 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 13 69 dep beta 2032:2035 arg1 1--> 2038:2041 1--> 2038:2041 1--> 2038:2041 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 70 theme beta- 1994:1998 arg1 1-->3 2018:2022 1-->3 2018:2022 1-->3 2018:2022 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 70 theme beta- 1994:1998 arg1 beta 2032:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1983:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1--> 1983:2041 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 3 71 theme improved 471:478 arg1 efficacy 480:487 the improved efficacy 467:487 the improved efficacy of the recombinant antithrombotic drug 467:526 In seeking to elucidate the molecular basis for the improved efficacy of the recombinant antithrombotic drug, we focused on the carbohydrate moiety of rHPC. 8130392 1 72 theme human 134:138 arg1 C 148:148 recombinant human protein C 122:148 recombinant human protein C expressed in human kidney 293 cells 122:184 are present in recombinant human protein C expressed in human kidney 293 cells. 8130392 9 73 link Asn-linked 1521:1530 arg1 oligosaccharides 1532:1547 the Asn-linked oligosaccharides 1517:1547 the Asn-linked oligosaccharides in rHPC 1517:1555 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 6 74 theme mol 887:889 arg1 rHPC 902:905 2.6 mol GalNAc/mol rHPC 883:905 2.6 mol GalNAc/mol rHPC 883:905 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 6 74 theme mol 887:889 arg1 N-acetylgalactosamine 860:880 N-acetylgalactosamine 860:880 N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides 860:941 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 1 75 theme kidney 169:174 arg1 cells 180:184 human kidney 293 cells 163:184 human kidney 293 cells 163:184 are present in recombinant human protein C expressed in human kidney 293 cells. 8130392 10 76 theme NeuAc 1627:1631 arg1 1-->4 1659:1663 1-->4 1659:1663 1-->4 1659:1663 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 10 76 theme NeuAc 1627:1631 arg1 beta 1653:1656 NeuAc alpha (2-->6)GalNAc beta 1627:1656 NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta 1627:1675 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 11 77 dep beta 1741:1744 arg1 1--> 1747:1750 1--> 1747:1750 1-->. 1747:1751 , and/or in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 10 78 theme alpha 1633:1637 arg1 1-->4 1659:1663 1-->4 1659:1663 1-->4 1659:1663 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 10 78 theme alpha 1633:1637 arg1 beta 1653:1656 NeuAc alpha (2-->6)GalNAc beta 1627:1656 NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta 1627:1675 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 79 theme beta 1591:1594 arg1 beta 1610:1613 GalNAc beta (1-->4)GlcNAc beta 1584:1613 GalNAc beta (1-->4)GlcNAc beta (1-->.) 1584:1621 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 3 80 theme recombinant 496:506 arg1 drug 523:526 the recombinant antithrombotic drug 492:526 the recombinant antithrombotic drug 492:526 In seeking to elucidate the molecular basis for the improved efficacy of the recombinant antithrombotic drug, we focused on the carbohydrate moiety of rHPC. 8130392 13 81 dep 16D 1864:1866 arg1 151 1869:1871 151 1869:1871 151 1869:1871 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 8 82 theme linkage 1220:1226 arg1 analysis 1228:1235 linkage analysis 1220:1235 linkage analysis 1220:1235 The most abundant oligosaccharides were structurally characterized by glycosyl composition and linkage analysis, in conjunction with 1H-NMR spectroscopy at 600 MHz. 8130392 9 83 dep beta 1610:1613 arg1 1--> 1616:1619 1--> 1616:1619 1-->. 1616:1620 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 11 84 theme 1-->3 1727:1731 arg1 beta 1741:1744 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1696:1744 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 1696:1752 , and/or in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 3 85 dep elucidate 433:441 arg1 seeking 422:428 seeking 422:428 seeking 422:428 In seeking to elucidate the molecular basis for the improved efficacy of the recombinant antithrombotic drug, we focused on the carbohydrate moiety of rHPC. 8130392 9 86 from oligosaccharides 1532:1547 arg1 rHPC 1552:1555 rHPC 1552:1555 rHPC 1552:1555 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 87 theme GlcNAc 1603:1608 arg1 beta 1610:1613 GalNAc beta (1-->4)GlcNAc beta 1584:1613 GalNAc beta (1-->4)GlcNAc beta (1-->.) 1584:1621 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 13 88 theme GalNAc 1987:1992 arg1 1-->3 2018:2022 1-->3 2018:2022 1-->3 2018:2022 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 88 theme GalNAc 1987:1992 arg1 beta 2032:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1983:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1--> 1983:2041 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 10 89 theme GlcNAc 1665:1670 arg1 beta 1672:1675 NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta 1627:1675 NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta 1627:1675 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 90 theme oligosaccharides 1429:1444 arg1 [formula 1483:1490 [formula 1483:1490 [formula: see text] 1483:1501 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 90 theme oligosaccharides 1429:1444 arg1 structure 1294:1302 The structure 1290:1302 The structure of the major neutral oligosaccharide in rHPC 1290:1347 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 90 theme oligosaccharides 1429:1444 arg1 representatives 1395:1409 Two representatives 1391:1409 : [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] 1369:1501 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 90 theme oligosaccharides 1429:1444 arg1 [formula 1459:1466 [formula 1459:1466 [formula: see text] 1459:1477 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 4 91 theme serine 629:634 arg1 C 584:584 Protein C 576:584 Protein C 576:584 Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. 8130392 4 91 theme serine 629:634 arg1 protease 636:643 a heavily post-translationally modified serine protease 589:643 a heavily post-translationally modified serine protease with four N-glycosylation sites 589:675 Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. 8130392 3 92 theme drug 523:526 arg1 efficacy 480:487 the improved efficacy 467:487 the improved efficacy of the recombinant antithrombotic drug 467:526 In seeking to elucidate the molecular basis for the improved efficacy of the recombinant antithrombotic drug, we focused on the carbohydrate moiety of rHPC. 8130392 13 93 located observed 1874:1881 arg2 16D 1864:1866 16D 1864:1866 16D 1864:1866 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 93 located observed 1874:1881 arg1 oligosaccharides 1901:1916 the Asn-linked oligosaccharides 1886:1916 the Asn-linked oligosaccharides of rHPC 1886:1924 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 6 94 theme Asn-linked 915:924 arg1 oligosaccharides 926:941 its Asn-linked oligosaccharides 911:941 its Asn-linked oligosaccharides 911:941 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 2 95 theme natural 402:408 arg1 protein 410:416 the natural protein 398:416 the natural protein 398:416 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 9 96 gly sialylated 1418:1427 arg1 oligosaccharides 1429:1444 the sialylated oligosaccharides 1414:1444 the sialylated oligosaccharides in rHPC are 1414:1456 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 8 97 theme 1H-NMR 1258:1263 arg1 spectroscopy 1265:1276 1H-NMR spectroscopy 1258:1276 1H-NMR spectroscopy at 600 MHz 1258:1287 The most abundant oligosaccharides were structurally characterized by glycosyl composition and linkage analysis, in conjunction with 1H-NMR spectroscopy at 600 MHz. 8130392 0 98 theme alpha 73:77 arg1 beta 94:97 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta 49:97 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 49:105 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 0 99 dep beta 94:97 arg1 1--> 100:103 1--> 100:103 1-->. 100:104 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 11 100 theme GlcNAc 1734:1739 arg1 beta 1741:1744 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1696:1744 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 1696:1752 , and/or in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 9 101 dep [formula 1483:1490 arg1 see 1493:1495 see 1493:1495 see text 1493:1500 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 0 102 theme 1-->3 80:84 arg1 beta 94:97 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta 49:97 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 49:105 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 2 103 contain has 260:262 arg2 activity 287:294 a higher anticoagulant activity 264:294 a higher anticoagulant activity than plasma HPC 264:310 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 2 103 contain has 260:262 arg1 rHPC 216:219 rHPC 216:219 rHPC 216:219 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 2 103 contain has 260:262 arg1 C 213:213 Recombinant human Protein C 187:213 Recombinant human Protein C (rHPC) 187:220 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 1 104 from present 111:117 arg1 C 148:148 recombinant human protein C 122:148 recombinant human protein C expressed in human kidney 293 cells 122:184 are present in recombinant human protein C expressed in human kidney 293 cells. 8130392 12 105 dep Chao 1808:1811 arg1 Cell 1848:1851 Cell 1848:1851 Cell 1848:1851 Since the latter trisaccharide was first [Yan, S.B., Chao, B.Y. and Van Halbeek,H. (1992) J. Cell. 8130392 4 106 gly N-glycosylation 655:669 arg2 sites 671:675 four N-glycosylation sites 650:675 four N-glycosylation sites 650:675 Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. 8130392 4 106 gly N-glycosylation 655:669 arg2 four 650:653 four 650:653 four 650:653 Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. 8130392 15 107 theme rHPC 2186:2189 arg1 activity 2174:2181 the higher anticoagulant activity 2149:2181 the higher anticoagulant activity of rHPC 2149:2189 The PC-293-containing oligosaccharides may contribute to the higher anticoagulant activity of rHPC as compared to plasma HPC. 8130392 7 108 theme anion-exchange 1094:1107 arg1 chromatography 1109:1122 high-pH anion-exchange chromatography 1086:1122 high-pH anion-exchange chromatography 1086:1122 The Asn-linked oligosaccharides of rHPC were released by N-glycanase and separated into 25 fractions by high-pH anion-exchange chromatography. 8130392 0 109 theme Asn-linked 6:15 arg1 oligosaccharides 17:32 Novel Asn-linked oligosaccharides 0:32 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 0:105 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 9 110 dep [formula 1459:1466 arg1 see 1469:1471 see 1469:1471 see text 1469:1476 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 11 111 theme beta 1703:1706 arg1 beta 1741:1744 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1696:1744 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 1696:1752 , and/or in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 5 112 theme fucose 741:746 arg1 content 748:754 a 5-fold higher fucose content 725:754 a 5-fold higher fucose content 725:754 Glycosyl composition analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC. 8130392 15 113 theme higher 2153:2158 arg1 activity 2174:2181 the higher anticoagulant activity 2149:2181 the higher anticoagulant activity of rHPC 2149:2189 The PC-293-containing oligosaccharides may contribute to the higher anticoagulant activity of rHPC as compared to plasma HPC. 8130392 10 114 theme beta 1653:1656 arg1 beta 1672:1675 NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta 1627:1675 NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta 1627:1675 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 2 115 theme circulatory 331:341 arg1 half-life 343:351 its in vivo circulatory half-life 319:351 its in vivo circulatory half-life 319:351 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 6 116 from N-acetylgalactosamine 860:880 arg1 oligosaccharides 926:941 its Asn-linked oligosaccharides 911:941 its Asn-linked oligosaccharides 911:941 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 3 117 theme carbohydrate 547:558 arg1 moiety 560:565 the carbohydrate moiety 543:565 the carbohydrate moiety of rHPC 543:573 In seeking to elucidate the molecular basis for the improved efficacy of the recombinant antithrombotic drug, we focused on the carbohydrate moiety of rHPC. 8130392 4 118 theme N-glycosylation 655:669 arg1 sites 671:675 four N-glycosylation sites 650:675 four N-glycosylation sites 650:675 Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. 8130392 2 119 theme in 323:324 arg1 half-life 343:351 its in vivo circulatory half-life 319:351 its in vivo circulatory half-life 319:351 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 0 120 theme GalNAc 49:54 arg1 1-->4 62:66 1-->4 62:66 1-->4 62:66 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 0 120 theme GalNAc 49:54 arg1 beta 56:59 GalNAc beta 49:59 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 49:105 Novel Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 6 121 theme plasma 950:955 arg1 HPC 957:959 plasma HPC 950:959 plasma HPC 950:959 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 14 122 theme PC-293 2072:2077 arg1 determinant 2079:2089 the PC-293 determinant 2068:2089 the PC-293 determinant 2068:2089 terminal trisaccharide the PC-293 determinant. 8130392 11 123 theme [Fuc 1715:1718 arg1 beta 1741:1744 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1696:1744 GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 1696:1752 , and/or in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 9 124 from rHPC 1344:1347 arg1 structure 1294:1302 The structure 1290:1302 The structure of the major neutral oligosaccharide in rHPC 1290:1347 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 124 from rHPC 1344:1347 arg1 representatives 1395:1409 Two representatives 1391:1409 : [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] 1369:1501 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 13 125 theme GlcNAc 2025:2030 arg1 1-->3 2018:2022 1-->3 2018:2022 1-->3 2018:2022 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 125 theme GlcNAc 2025:2030 arg1 beta 2032:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1983:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1--> 1983:2041 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 2 126 dep in 323:324 arg1 vivo 326:329 vivo 326:329 vivo 326:329 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 8130392 9 127 theme neutral 1317:1323 arg1 oligosaccharide 1325:1339 the major neutral oligosaccharide 1307:1339 the major neutral oligosaccharide in rHPC 1307:1347 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 9 128 from oligosaccharide 1325:1339 arg1 rHPC 1344:1347 rHPC 1344:1347 rHPC 1344:1347 The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 13 129 theme [Fuc 2006:2009 arg1 1-->3 2018:2022 1-->3 2018:2022 1-->3 2018:2022 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 13 129 theme [Fuc 2006:2009 arg1 beta 2032:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta 1983:2035 the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1--> 1983:2041 Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) 8130392 10 130 theme GalNAc 1646:1651 arg1 1-->4 1659:1663 1-->4 1659:1663 1-->4 1659:1663 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 10 130 theme GalNAc 1646:1651 arg1 beta 1653:1656 NeuAc alpha (2-->6)GalNAc beta 1627:1656 NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta 1627:1675 , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.) 8130392 1 131 theme human 163:167 arg1 cells 180:184 human kidney 293 cells 163:184 human kidney 293 cells 163:184 are present in recombinant human protein C expressed in human kidney 293 cells. 8130392 7 132 link Asn-linked 986:995 arg1 oligosaccharides 997:1012 The Asn-linked oligosaccharides 982:1012 The Asn-linked oligosaccharides of rHPC 982:1020 The Asn-linked oligosaccharides of rHPC were released by N-glycanase and separated into 25 fractions by high-pH anion-exchange chromatography. 8130392 4 133 with protease 636:643 arg1 sites 671:675 four N-glycosylation sites 650:675 four N-glycosylation sites 650:675 Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. 8130392 6 134 contain contains 851:858 arg1 rHPC 846:849 rHPC 846:849 rHPC 846:849 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 6 134 contain contains 851:858 arg2 N-acetylgalactosamine 860:880 N-acetylgalactosamine 860:880 N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides 860:941 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 6 134 contain contains 851:858 arg2 rHPC 902:905 2.6 mol GalNAc/mol rHPC 883:905 2.6 mol GalNAc/mol rHPC 883:905 In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. 8130392 2 135 theme anticoagulant 273:285 arg1 activity 287:294 a higher anticoagulant activity 264:294 a higher anticoagulant activity than plasma HPC 264:310 Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. 1388166 6 0 theme same 1167:1170 arg1 properties 1172:1181 the same properties 1163:1181 the same properties as those expressed in the pituitary 1163:1217 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 5 1 from plasma 1059:1064 arg1 clearance 1044:1052 their rapid clearance 1032:1052 their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells 1032:1115 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 4 2 theme 6-9 696:698 arg1 residues 700:707 the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues 659:707 the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites 659:745 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 4 3 theme 2Man 888:891 arg1 beta 880:883 a GalNAc beta 1,4GlcNAc beta 1 856:885 a GalNAc beta 1,4GlcNAc beta 1 856:885 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 4 3 theme 2Man 888:891 arg1 alpha-4-sulfotransferase 893:916 2Man alpha-4-sulfotransferase 888:916 2Man alpha-4-sulfotransferase 888:916 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 7 4 theme Asn-linked 1450:1459 arg1 oligosaccharides 1461:1476 sulfated Asn-linked oligosaccharides 1441:1476 sulfated Asn-linked oligosaccharides 1441:1476 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 4 5 theme N-terminal 709:718 arg1 residues 700:707 the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues 659:707 the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites 659:745 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 2 6 theme oligosaccharides 302:317 arg1 % 293:293 greater than 70% 278:293 greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells 278:360 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 2 6 theme oligosaccharides 302:317 arg1 oligosaccharides 302:317 the oligosaccharides 298:317 the oligosaccharides on recombinant TFPI expressed in 293 cells 298:360 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 0 7 theme 1,2 122:124 arg1 alpha 131:135 4GlcNAc beta 1,2 Mana alpha 109:135 4GlcNAc beta 1,2 Mana alpha 109:135 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 0 7 theme 1,2 122:124 arg1 beta 101:104 SO4-4GalNAc beta 1 89:106 SO4-4GalNAc beta 1 89:106 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 1 8 theme endothelial 189:199 arg1 cells 201:205 endothelial cells 189:205 endothelial cells 189:205 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 8 9 theme sequence 1497:1504 arg1 residues 1521:1528 the sequence Pro-Phe-Lys, 9 residues 1493:1528 residues 1521:1528 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 4 10 theme motif 674:678 arg1 residues 700:707 the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues 659:707 the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites 659:745 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 7 11 theme CHO 1414:1416 arg1 cells 1418:1422 CHO cells 1414:1422 CHO cells 1414:1422 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 5 12 theme reticuloendothelial 1091:1109 arg1 cells 1111:1115 hepatic reticuloendothelial cells 1083:1115 hepatic reticuloendothelial cells 1083:1115 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 5 13 theme sulfated 960:967 arg1 oligosaccharides 969:984 The sulfated oligosaccharides 956:984 The sulfated oligosaccharides present on these hormones 956:1010 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 5 13 theme sulfated 960:967 arg1 responsible 1016:1026 responsible 1016:1026 responsible 1016:1026 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 9 14 theme hepatic 1757:1763 arg1 cells 1785:1789 hepatic reticuloendothelial cells 1757:1789 hepatic reticuloendothelial cells 1757:1789 rTFPI produced by 293 cells, but not that produced by CHO cells, is bound by the receptor on hepatic reticuloendothelial cells suggesting the sulfated structures play a role in the biologic behavior of TFPI. 1388166 6 15 theme lower 1267:1271 arg1 levels 1273:1278 lower levels 1267:1278 lower levels in endothelial cells 1267:1299 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 4 16 theme specific 764:771 arg1 addition 773:780 the specific addition 760:780 the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins 760:845 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 6 17 from levels 1273:1278 arg1 cells 1295:1299 endothelial cells 1283:1299 endothelial cells 1283:1299 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 5 18 theme present 986:992 arg1 oligosaccharides 969:984 The sulfated oligosaccharides 956:984 The sulfated oligosaccharides present on these hormones 956:1010 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 5 18 theme present 986:992 arg1 responsible 1016:1026 responsible 1016:1026 responsible 1016:1026 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 2 19 from % 293:293 arg1 TFPI 334:337 recombinant TFPI 322:337 recombinant TFPI expressed in 293 cells 322:360 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 4 20 theme Asn 723:725 arg1 sites 741:745 Asn glycosylation sites 723:745 Asn glycosylation sites 723:745 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 1 21 theme factor 145:150 arg1 TFPI 171:174 TFPI 171:174 TFPI 171:174 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 1 21 theme factor 145:150 arg1 inhibitor 160:168 Tissue factor pathway inhibitor 138:168 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells 138:205 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 7 22 link Asn-linked 1450:1459 arg1 oligosaccharides 1461:1476 sulfated Asn-linked oligosaccharides 1441:1476 sulfated Asn-linked oligosaccharides 1441:1476 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 0 23 from oligosaccharides 22:37 arg1 inhibitor 64:72 tissue factor pathway inhibitor 42:72 tissue factor pathway inhibitor 42:72 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 9 24 theme reticuloendothelial 1765:1783 arg1 cells 1785:1789 hepatic reticuloendothelial cells 1757:1789 hepatic reticuloendothelial cells 1757:1789 rTFPI produced by 293 cells, but not that produced by CHO cells, is bound by the receptor on hepatic reticuloendothelial cells suggesting the sulfated structures play a role in the biologic behavior of TFPI. 1388166 0 25 theme SO4-4GalNAc 89:99 arg1 alpha 131:135 4GlcNAc beta 1,2 Mana alpha 109:135 4GlcNAc beta 1,2 Mana alpha 109:135 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 0 25 theme SO4-4GalNAc 89:99 arg1 beta 101:104 SO4-4GalNAc beta 1 89:106 SO4-4GalNAc beta 1 89:106 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 4 26 theme oligosaccharide 799:813 arg1 acceptor 815:822 the oligosaccharide acceptor 795:822 the oligosaccharide acceptor on these glycoproteins 795:845 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 0 27 theme 4GlcNAc 109:115 arg1 alpha 131:135 4GlcNAc beta 1,2 Mana alpha 109:135 4GlcNAc beta 1,2 Mana alpha 109:135 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 0 27 theme 4GlcNAc 109:115 arg1 beta 101:104 SO4-4GalNAc beta 1 89:106 SO4-4GalNAc beta 1 89:106 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 9 28 dep rTFPI 1664:1668 arg1 produced 1706:1713 produced 1706:1713 produced by CHO cells 1706:1726 rTFPI produced by 293 cells, but not that produced by CHO cells, is bound by the receptor on hepatic reticuloendothelial cells suggesting the sulfated structures play a role in the biologic behavior of TFPI. 1388166 5 29 theme rapid 1038:1042 arg1 clearance 1044:1052 their rapid clearance 1032:1052 their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells 1032:1115 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 7 30 theme transferase 1379:1389 arg1 levels 1362:1367 detectable levels 1351:1367 detectable levels of either transferase and rTFPI expressed in CHO cells 1351:1422 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 8 31 contain contains 1484:1491 arg1 TFPI 1479:1482 TFPI 1479:1482 TFPI 1479:1482 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 8 31 contain contains 1484:1491 arg2 TFPI 1479:1482 TFPI 1479:1482 TFPI 1479:1482 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 8 31 contain contains 1484:1491 arg1 position 1570:1577 position 228 1570:1581 position 228 1570:1581 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 8 31 contain contains 1484:1491 arg2 residues 1521:1528 the sequence Pro-Phe-Lys, 9 residues 1493:1528 residues 1521:1528 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 2 32 theme sequence 381:388 arg1 alpha 431:435 2Man alpha 426:435 2Man alpha 426:435 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 2 32 theme sequence 381:388 arg1 beta 402:405 the sequence SO4-4GalNAc beta 1 377:407 the sequence SO4-4GalNAc beta 1 377:407 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 2 32 theme sequence 381:388 arg1 beta 418:421 4GlcNAc beta 1 410:423 4GlcNAc beta 1 410:423 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 9 33 theme biologic 1845:1852 arg1 behavior 1854:1861 the biologic behavior 1841:1861 the biologic behavior of TFPI 1841:1869 rTFPI produced by 293 cells, but not that produced by CHO cells, is bound by the receptor on hepatic reticuloendothelial cells suggesting the sulfated structures play a role in the biologic behavior of TFPI. 1388166 4 34 dep accounts 747:754 arg1 whereas 848:854 whereas 848:854 whereas 848:854 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 7 35 theme detectable 1351:1360 arg1 levels 1362:1367 detectable levels 1351:1367 detectable levels of either transferase and rTFPI expressed in CHO cells 1351:1422 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 4 36 theme GalNAc 858:863 arg1 beta 880:883 a GalNAc beta 1,4GlcNAc beta 1 856:885 a GalNAc beta 1,4GlcNAc beta 1 856:885 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 4 36 theme GalNAc 858:863 arg1 alpha-4-sulfotransferase 893:916 2Man alpha-4-sulfotransferase 888:916 2Man alpha-4-sulfotransferase 888:916 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 0 37 theme tissue 42:47 arg1 inhibitor 64:72 tissue factor pathway inhibitor 42:72 tissue factor pathway inhibitor 42:72 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 4 38 gly glycoproteins 833:845 arg1 glycoproteins 833:845 these glycoproteins 827:845 these glycoproteins 827:845 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 8 39 theme recognition 1615:1625 arg1 sequence 1627:1634 the recognition sequence 1611:1634 the recognition sequence for the GalNAc-transferase 1611:1661 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 8 39 theme recognition 1615:1625 arg1 tripeptide 1589:1598 this tripeptide 1584:1598 this tripeptide 1584:1598 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 4 40 theme 1,4GlcNAc 870:878 arg1 beta 880:883 a GalNAc beta 1,4GlcNAc beta 1 856:885 a GalNAc beta 1,4GlcNAc beta 1 856:885 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 4 40 theme 1,4GlcNAc 870:878 arg1 alpha-4-sulfotransferase 893:916 2Man alpha-4-sulfotransferase 888:916 2Man alpha-4-sulfotransferase 888:916 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 0 41 theme pathway 56:62 arg1 inhibitor 64:72 tissue factor pathway inhibitor 42:72 tissue factor pathway inhibitor 42:72 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 5 42 theme hepatic 1083:1089 arg1 cells 1111:1115 hepatic reticuloendothelial cells 1083:1115 hepatic reticuloendothelial cells 1083:1115 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 1 43 theme sulfated 216:223 arg1 oligosaccharides 236:251 sulfated Asn-linked oligosaccharides 216:251 sulfated Asn-linked oligosaccharides 216:251 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 7 44 theme CHO 1325:1327 arg1 cells 1330:1334 Chinese hamster ovary (CHO) cells 1302:1334 Chinese hamster ovary (CHO) cells 1302:1334 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 7 45 theme ovary 1318:1322 arg1 cells 1330:1334 Chinese hamster ovary (CHO) cells 1302:1334 Chinese hamster ovary (CHO) cells 1302:1334 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 8 46 theme glycosylation 1548:1560 arg1 site 1562:1565 the glycosylation site 1544:1565 the glycosylation site 1544:1565 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 5 47 attach present 986:992 arg1 hormones 1003:1010 these hormones 997:1010 these hormones 997:1010 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 5 47 attach present 986:992 arg2 oligosaccharides 969:984 The sulfated oligosaccharides 956:984 The sulfated oligosaccharides present on these hormones 956:1010 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 5 47 attach present 986:992 arg2 responsible 1016:1026 responsible 1016:1026 responsible 1016:1026 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 2 48 from TFPI 334:337 arg1 % 293:293 greater than 70% 278:293 greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells 278:360 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 2 48 from TFPI 334:337 arg1 oligosaccharides 302:317 the oligosaccharides 298:317 the oligosaccharides on recombinant TFPI expressed in 293 cells 298:360 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 7 49 theme Chinese 1302:1308 arg1 cells 1330:1334 Chinese hamster ovary (CHO) cells 1302:1334 Chinese hamster ovary (CHO) cells 1302:1334 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 0 50 link asparagine-linked 4:20 arg1 oligosaccharides 22:37 The asparagine-linked oligosaccharides 0:37 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor 0:72 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 9 51 theme CHO 1718:1720 arg1 cells 1722:1726 CHO cells 1718:1726 CHO cells 1718:1726 rTFPI produced by 293 cells, but not that produced by CHO cells, is bound by the receptor on hepatic reticuloendothelial cells suggesting the sulfated structures play a role in the biologic behavior of TFPI. 1388166 6 52 theme high 1235:1238 arg1 levels 1240:1245 high levels 1235:1245 high levels in 293 cells 1235:1258 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 4 53 theme Pro-Xaa-Arg/Lys 680:694 arg1 residues 700:707 the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues 659:707 the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites 659:745 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 0 54 theme Mana 126:129 arg1 alpha 131:135 4GlcNAc beta 1,2 Mana alpha 109:135 4GlcNAc beta 1,2 Mana alpha 109:135 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 0 54 theme Mana 126:129 arg1 beta 101:104 SO4-4GalNAc beta 1 89:106 SO4-4GalNAc beta 1 89:106 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 1 55 link Asn-linked 225:234 arg1 oligosaccharides 236:251 sulfated Asn-linked oligosaccharides 216:251 sulfated Asn-linked oligosaccharides 216:251 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 8 56 theme Pro-Phe-Lys 1506:1516 arg1 residues 1521:1528 the sequence Pro-Phe-Lys, 9 residues 1493:1528 residues 1521:1528 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 7 57 theme sulfated 1441:1448 arg1 oligosaccharides 1461:1476 sulfated Asn-linked oligosaccharides 1441:1476 sulfated Asn-linked oligosaccharides 1441:1476 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 3 58 theme anterior 602:609 arg1 pituitary 611:619 the anterior pituitary 598:619 the anterior pituitary 598:619 Oligosaccharides terminating with this sequence have previously been described on lutropin, thyrotropin, and pro-opiomelanocortin: glycoproteins synthesized in the anterior pituitary. 1388166 5 59 from receptor 1071:1078 arg1 cells 1111:1115 hepatic reticuloendothelial cells 1083:1115 hepatic reticuloendothelial cells 1083:1115 The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. 1388166 6 60 theme endothelial 1283:1293 arg1 cells 1295:1299 endothelial cells 1283:1299 endothelial cells 1283:1299 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 4 61 theme tripeptide 663:672 arg1 residues 700:707 the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues 659:707 the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites 659:745 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 7 62 contain contain 1343:1349 arg2 levels 1362:1367 detectable levels 1351:1367 detectable levels of either transferase and rTFPI expressed in CHO cells 1351:1422 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 7 62 contain contain 1343:1349 arg1 cells 1330:1334 Chinese hamster ovary (CHO) cells 1302:1334 Chinese hamster ovary (CHO) cells 1302:1334 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 8 63 gly glycosylation 1548:1560 arg2 site 1562:1565 the glycosylation site 1544:1565 the glycosylation site 1544:1565 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 8 64 theme N-terminal 1530:1539 arg1 residues 1521:1528 the sequence Pro-Phe-Lys, 9 residues 1493:1528 residues 1521:1528 TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. 1388166 3 65 gly glycoproteins 569:581 arg1 glycoproteins 569:581 glycoproteins 569:581 glycoproteins synthesized in the anterior pituitary 569:619 Oligosaccharides terminating with this sequence have previously been described on lutropin, thyrotropin, and pro-opiomelanocortin: glycoproteins synthesized in the anterior pituitary. 1388166 4 66 gly glycosylation 727:739 arg2 sites 741:745 Asn glycosylation sites 723:745 Asn glycosylation sites 723:745 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 4 67 theme sulfate 947:953 arg1 addition 935:942 the addition 931:942 the addition of sulfate 931:953 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 1 68 theme Tissue 138:143 arg1 TFPI 171:174 TFPI 171:174 TFPI 171:174 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 1 68 theme Tissue 138:143 arg1 inhibitor 160:168 Tissue factor pathway inhibitor 138:168 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells 138:205 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 9 69 from receptor 1745:1752 arg1 cells 1785:1789 hepatic reticuloendothelial cells 1757:1789 hepatic reticuloendothelial cells 1757:1789 rTFPI produced by 293 cells, but not that produced by CHO cells, is bound by the receptor on hepatic reticuloendothelial cells suggesting the sulfated structures play a role in the biologic behavior of TFPI. 1388166 7 70 theme rTFPI 1395:1399 arg1 levels 1362:1367 detectable levels 1351:1367 detectable levels of either transferase and rTFPI expressed in CHO cells 1351:1422 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 1388166 1 71 theme pathway 152:158 arg1 TFPI 171:174 TFPI 171:174 TFPI 171:174 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 1 71 theme pathway 152:158 arg1 inhibitor 160:168 Tissue factor pathway inhibitor 138:168 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells 138:205 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 9 72 theme sulfated 1806:1813 arg1 structures 1815:1824 the sulfated structures 1802:1824 the sulfated structures 1802:1824 rTFPI produced by 293 cells, but not that produced by CHO cells, is bound by the receptor on hepatic reticuloendothelial cells suggesting the sulfated structures play a role in the biologic behavior of TFPI. 1388166 4 73 theme glycosylation 727:739 arg1 sites 741:745 Asn glycosylation sites 723:745 Asn glycosylation sites 723:745 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 4 74 from acceptor 815:822 arg1 glycoproteins 833:845 these glycoproteins 827:845 these glycoproteins 827:845 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 2 75 from oligosaccharides 302:317 arg1 TFPI 334:337 recombinant TFPI 322:337 recombinant TFPI expressed in 293 cells 322:360 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 6 76 from levels 1240:1245 arg1 cells 1254:1258 293 cells 1250:1258 293 cells 1250:1258 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 0 77 theme beta 117:120 arg1 alpha 131:135 4GlcNAc beta 1,2 Mana alpha 109:135 4GlcNAc beta 1,2 Mana alpha 109:135 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 0 77 theme beta 117:120 arg1 beta 101:104 SO4-4GalNAc beta 1 89:106 SO4-4GalNAc beta 1 89:106 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 2 78 theme SO4-4GalNAc 390:400 arg1 alpha 431:435 2Man alpha 426:435 2Man alpha 426:435 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 2 78 theme SO4-4GalNAc 390:400 arg1 beta 402:405 the sequence SO4-4GalNAc beta 1 377:407 the sequence SO4-4GalNAc beta 1 377:407 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 2 78 theme SO4-4GalNAc 390:400 arg1 beta 418:421 4GlcNAc beta 1 410:423 4GlcNAc beta 1 410:423 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 0 79 theme asparagine-linked 4:20 arg1 oligosaccharides 22:37 The asparagine-linked oligosaccharides 0:37 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor 0:72 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 6 80 theme sulfotransferase 1130:1145 arg1 activities 1147:1156 GalNAc- and sulfotransferase activities 1118:1156 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary 1118:1217 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 2 81 theme 2Man 426:429 arg1 alpha 431:435 2Man alpha 426:435 2Man alpha 426:435 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 2 81 theme 2Man 426:429 arg1 beta 402:405 the sequence SO4-4GalNAc beta 1 377:407 the sequence SO4-4GalNAc beta 1 377:407 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 6 82 theme GalNAc- 1118:1124 arg1 activities 1147:1156 GalNAc- and sulfotransferase activities 1118:1156 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary 1118:1217 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 4 83 theme GalNAc 785:790 arg1 addition 773:780 the specific addition 760:780 the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins 760:845 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 2 84 theme 4GlcNAc 410:416 arg1 beta 402:405 the sequence SO4-4GalNAc beta 1 377:407 the sequence SO4-4GalNAc beta 1 377:407 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 2 84 theme 4GlcNAc 410:416 arg1 beta 418:421 4GlcNAc beta 1 410:423 4GlcNAc beta 1 410:423 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 0 85 theme factor 49:54 arg1 inhibitor 64:72 tissue factor pathway inhibitor 42:72 tissue factor pathway inhibitor 42:72 The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 1388166 9 86 theme TFPI 1866:1869 arg1 behavior 1854:1861 the biologic behavior 1841:1861 the biologic behavior of TFPI 1841:1869 rTFPI produced by 293 cells, but not that produced by CHO cells, is bound by the receptor on hepatic reticuloendothelial cells suggesting the sulfated structures play a role in the biologic behavior of TFPI. 1388166 6 87 with activities 1147:1156 arg1 properties 1172:1181 the same properties 1163:1181 the same properties as those expressed in the pituitary 1163:1217 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 1 88 contain contains 207:214 arg2 oligosaccharides 236:251 sulfated Asn-linked oligosaccharides 216:251 sulfated Asn-linked oligosaccharides 216:251 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 1 88 contain contains 207:214 arg1 TFPI 171:174 TFPI 171:174 TFPI 171:174 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 1 88 contain contains 207:214 arg1 inhibitor 160:168 Tissue factor pathway inhibitor 138:168 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells 138:205 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 4 89 theme beta 865:868 arg1 beta 880:883 a GalNAc beta 1,4GlcNAc beta 1 856:885 a GalNAc beta 1,4GlcNAc beta 1 856:885 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 4 89 theme beta 865:868 arg1 alpha-4-sulfotransferase 893:916 2Man alpha-4-sulfotransferase 888:916 2Man alpha-4-sulfotransferase 888:916 A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. 1388166 6 90 located detected 1223:1230 arg1 levels 1240:1245 high levels 1235:1245 high levels in 293 cells 1235:1258 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 6 90 located detected 1223:1230 arg2 activities 1147:1156 GalNAc- and sulfotransferase activities 1118:1156 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary 1118:1217 GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. 1388166 2 91 theme recombinant 322:332 arg1 TFPI 334:337 recombinant TFPI 322:337 recombinant TFPI expressed in 293 cells 322:360 We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. 1388166 1 92 theme Asn-linked 225:234 arg1 oligosaccharides 236:251 sulfated Asn-linked oligosaccharides 216:251 sulfated Asn-linked oligosaccharides 216:251 Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. 1388166 7 93 theme hamster 1310:1316 arg1 cells 1330:1334 Chinese hamster ovary (CHO) cells 1302:1334 Chinese hamster ovary (CHO) cells 1302:1334 Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. 2592374 7 0 theme additional 1442:1451 arg1 unit 1471:1474 an additional hexose-hexosamine unit 1439:1474 an additional hexose-hexosamine unit 1439:1474 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 7 1 theme acid 1415:1418 arg1 groups 1428:1433 three N-acetylneuraminic acid (NeuAc) groups 1390:1433 three N-acetylneuraminic acid (NeuAc) groups 1390:1433 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 1 2 theme mass 235:238 arg1 mapping 262:268 mass spectrometric peptide mapping 235:268 mass spectrometric peptide mapping 235:268 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 6 3 theme following 1267:1275 arg1 structures 1289:1298 the following biantennary structures 1263:1298 the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1 1263:1350 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 1 4 theme receptor 156:163 arg1 form 140:143 a soluble form 130:143 a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells 130:211 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 6 5 dep see 1311:1313 arg1 Formula 1302:1308 Formula 1302:1308 Formula 1302:1308 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 4 6 theme disulfides 821:830 arg1 arrangements 805:816 No other arrangements 796:816 No other arrangements of disulfides 796:830 No other arrangements of disulfides were detected. 2592374 6 7 theme specific 1159:1166 arg1 sites 1179:1183 the specific attachment sites 1155:1183 the specific attachment sites 1155:1183 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 5 8 theme Carbohydrate 847:858 arg1 mapping 860:866 Carbohydrate mapping 847:866 Carbohydrate mapping by mass spectrometry 847:887 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 7 9 theme Minor 1353:1357 arg1 components 1372:1381 Minor carbohydrate components 1353:1381 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups 1353:1433 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 3 10 theme previous 702:709 arg1 studies 711:717 previous studies 702:717 previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse 702:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 3 11 theme disulfide 513:521 arg1 bonds 523:527 the three disulfide bonds 503:527 the three disulfide bonds in recombinant sCD4 503:547 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 6 12 theme oligosaccharides 1241:1256 arg1 families 1229:1236 both families 1224:1236 both families of oligosaccharides 1224:1256 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 1 13 theme Chinese 185:191 arg1 cells 207:211 Chinese hamster ovary cells 185:211 Chinese hamster ovary cells 185:211 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 6 14 theme families 1229:1236 arg1 components 1210:1219 the major components 1200:1219 the major components of both families of oligosaccharides 1200:1256 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 3 15 theme disulfide 733:741 arg1 bonding 743:749 intrachain disulfide bonding 722:749 intrachain disulfide bonding in T4 antigens derived from sheep and mouse 722:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 6 16 from each 1147:1150 arg1 oligosaccharides 1127:1142 oligosaccharides 1127:1142 oligosaccharides at each of the specific attachment sites 1127:1183 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 6 16 from each 1147:1150 arg1 family 1117:1122 the heterogeneous family 1099:1122 the heterogeneous family of oligosaccharides at each of the specific attachment sites 1099:1183 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 6 17 theme major 1204:1208 arg1 components 1210:1219 the major components 1200:1219 the major components of both families of oligosaccharides 1200:1256 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 0 18 theme soluble 62:68 arg1 receptor 74:81 a recombinant soluble CD4 receptor 48:81 a recombinant soluble CD4 receptor 48:81 Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. 2592374 1 19 theme form 140:143 arg1 structure 117:125 The primary structure 105:125 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells 105:211 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 3 20 from arrangement 488:498 arg1 sCD4 544:547 recombinant sCD4 532:547 recombinant sCD4 532:547 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 0 21 theme receptor 74:81 arg1 Protein 0:6 Protein 0:6 Protein 0:6 Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. 2592374 0 21 theme receptor 74:81 arg1 analysis 36:43 carbohydrate structural analysis 12:43 carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry 12:102 Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. 2592374 0 22 theme mass 86:89 arg1 spectrometry 91:102 mass spectrometry 86:102 mass spectrometry 86:102 Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. 2592374 2 23 theme ends 477:480 arg1 absence 458:464 the absence 454:464 the absence of "ragged ends 454:480 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 1 24 dep spectrometry 290:301 arg1 tandem 278:283 tandem 278:283 tandem 278:283 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 2 25 theme NH2 422:424 arg1 terminal 435:442 the NH2 and COOH terminal 418:442 terminal 435:442 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 2 26 theme acid-long 352:360 arg1 sequence 362:369 the 369-amino acid-long sequence 338:369 the 369-amino acid-long sequence 338:369 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 1 27 theme spectrometric 240:252 arg1 mapping 262:268 mass spectrometric peptide mapping 235:268 mass spectrometric peptide mapping 235:268 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 6 28 contain have 1258:1261 arg1 components 1210:1219 the major components 1200:1219 the major components of both families of oligosaccharides 1200:1256 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 6 28 contain have 1258:1261 arg2 structures 1289:1298 the following biantennary structures 1263:1298 the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1 1263:1350 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 6 29 theme mass 1053:1056 arg1 spectrometry 1058:1069 mass spectrometry 1053:1069 mass spectrometry 1053:1069 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 2 30 dep corroborated 318:329 arg1 " 482:482 " 482:482 " 482:482 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 3 31 from sCD4 544:547 arg1 arrangement 488:498 The arrangement 484:498 The arrangement of the three disulfide bonds in recombinant sCD4 484:547 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 0 32 theme carbohydrate 12:23 arg1 analysis 36:43 carbohydrate structural analysis 12:43 carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry 12:102 Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. 2592374 7 33 contain having 1383:1388 arg1 components 1372:1381 Minor carbohydrate components 1353:1381 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups 1353:1433 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 7 33 contain having 1383:1388 arg2 groups 1428:1433 three N-acetylneuraminic acid (NeuAc) groups 1390:1433 three N-acetylneuraminic acid (NeuAc) groups 1390:1433 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 5 34 theme Asn-linked 931:940 arg1 sites 956:960 both potential Asn-linked glycosylation sites 916:960 both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) 916:988 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 3 35 theme performance 612:622 arg1 chromatography 631:644 comparative high performance liquid chromatography 595:644 comparative high performance liquid chromatography 595:644 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 7 36 theme performance 1498:1508 arg1 chromatography 1525:1538 high performance anion-exchange chromatography 1493:1538 high performance anion-exchange chromatography 1493:1538 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 2 37 theme COOH 430:433 arg1 terminal 435:442 the NH2 and COOH terminal 418:442 terminal 435:442 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 3 38 from antigens 757:764 arg1 studies 711:717 previous studies 702:717 previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse 702:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 3 39 theme comparative 595:605 arg1 chromatography 631:644 comparative high performance liquid chromatography 595:644 comparative high performance liquid chromatography 595:644 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 6 40 from family 1117:1122 arg1 sites 1179:1183 the specific attachment sites 1155:1183 the specific attachment sites 1155:1183 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 6 40 from family 1117:1122 arg1 each 1147:1150 each 1147:1150 each 1147:1150 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 1 41 theme mass 285:288 arg1 spectrometry 290:301 and tandem mass spectrometry 274:301 spectrometry 290:301 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 6 42 theme oligosaccharides 1127:1142 arg1 family 1117:1122 the heterogeneous family 1099:1122 the heterogeneous family of oligosaccharides at each of the specific attachment sites 1099:1183 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 1 43 theme hamster 193:199 arg1 cells 207:211 Chinese hamster ovary cells 185:211 Chinese hamster ovary cells 185:211 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 7 44 theme N-acetylneuraminic 1396:1413 arg1 NeuAc 1421:1425 NeuAc 1421:1425 NeuAc 1421:1425 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 7 44 theme N-acetylneuraminic 1396:1413 arg1 acid 1415:1418 N-acetylneuraminic acid 1396:1418 three N-acetylneuraminic acid (NeuAc) groups 1390:1433 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 6 45 theme family 1117:1122 arg1 characterization 1033:1048 Structural characterization 1022:1048 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites 1022:1183 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 5 46 contain have 990:993 arg1 sites 956:960 both potential Asn-linked glycosylation sites 916:960 both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) 916:988 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 5 46 contain have 990:993 arg2 oligosaccharides 995:1010 oligosaccharides 995:1010 oligosaccharides attached 995:1019 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 5 47 link Asn-linked 931:940 arg1 sites 956:960 both potential Asn-linked glycosylation sites 916:960 both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) 916:988 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 7 48 theme hexose-hexosamine 1453:1469 arg1 unit 1471:1474 an additional hexose-hexosamine unit 1439:1474 an additional hexose-hexosamine unit 1439:1474 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 5 49 from sites 956:960 arg1 sCD4 965:968 sCD4 965:968 sCD4 (Asn271 and Asn300) 965:988 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 6 50 dep structures 1289:1298 arg1 see 1311:1313 see 1311:1313 see text 1311:1318 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 6 51 theme biantennary 1277:1287 arg1 structures 1289:1298 the following biantennary structures 1263:1298 the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1 1263:1350 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 1 52 theme CD4 152:154 arg1 sCD4 166:169 sCD4 166:169 sCD4 166:169 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 1 52 theme CD4 152:154 arg1 receptor 156:163 the CD4 receptor 148:163 the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells 148:211 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 4 53 theme other 799:803 arg1 arrangements 805:816 No other arrangements 796:816 No other arrangements of disulfides 796:830 No other arrangements of disulfides were detected. 2592374 6 54 theme attachment 1168:1177 arg1 sites 1179:1183 the specific attachment sites 1155:1183 the specific attachment sites 1155:1183 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 3 55 theme bonds 523:527 arg1 arrangement 488:498 The arrangement 484:498 The arrangement of the three disulfide bonds in recombinant sCD4 484:547 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 3 56 theme intrachain 722:731 arg1 bonding 743:749 intrachain disulfide bonding 722:749 intrachain disulfide bonding in T4 antigens derived from sheep and mouse 722:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 7 57 theme carbohydrate 1359:1370 arg1 components 1372:1381 Minor carbohydrate components 1353:1381 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups 1353:1433 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 3 58 theme T4 754:755 arg1 antigens 757:764 T4 antigens 754:764 T4 antigens derived from sheep and mouse 754:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 3 59 theme recombinant 532:542 arg1 sCD4 544:547 recombinant sCD4 532:547 recombinant sCD4 532:547 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 1 60 theme primary 109:115 arg1 structure 117:125 The primary structure 105:125 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells 105:211 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 5 61 dep sCD4 965:968 arg1 Asn300 982:987 Asn300 982:987 Asn300 982:987 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 5 61 dep sCD4 965:968 arg1 Asn271 971:976 Asn271 971:976 Asn271 971:976 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 3 62 theme bonding 743:749 arg1 studies 711:717 previous studies 702:717 previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse 702:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 3 63 theme mass 573:576 arg1 spectrometry 578:589 mass spectrometry 573:589 mass spectrometry 573:589 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 3 64 from bonds 523:527 arg1 sCD4 544:547 recombinant sCD4 532:547 recombinant sCD4 532:547 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 0 65 theme CD4 70:72 arg1 receptor 74:81 a recombinant soluble CD4 receptor 48:81 a recombinant soluble CD4 receptor 48:81 Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. 2592374 5 66 used used 893:896 arg2 mapping 860:866 Carbohydrate mapping 847:866 Carbohydrate mapping by mass spectrometry 847:887 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 1 67 theme soluble 132:138 arg1 form 140:143 a soluble form 130:143 a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells 130:211 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 5 68 gly glycosylation 942:954 arg2 sites 956:960 both potential Asn-linked glycosylation sites 916:960 both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) 916:988 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 5 69 theme mass 871:874 arg1 spectrometry 876:887 mass spectrometry 871:887 mass spectrometry 871:887 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 3 70 from bonding 743:749 arg1 antigens 757:764 T4 antigens 754:764 T4 antigens derived from sheep and mouse 754:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 5 71 theme glycosylation 942:954 arg1 sites 956:960 both potential Asn-linked glycosylation sites 916:960 both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) 916:988 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 6 72 theme methylation 1075:1085 arg1 analysis 1087:1094 methylation analysis 1075:1094 methylation analysis 1075:1094 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 2 73 theme ragged 470:475 arg1 ends 477:480 "ragged ends 469:480 "ragged ends 469:480 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 3 74 from studies 711:717 arg1 antigens 757:764 T4 antigens 754:764 T4 antigens derived from sheep and mouse 754:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 2 75 theme sequence 362:369 arg1 sequence 362:369 the 369-amino acid-long sequence 338:369 the 369-amino acid-long sequence 338:369 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 2 75 theme sequence 362:369 arg1 % 333:333 95% 331:333 95% of the 369-amino acid-long sequence 331:369 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 3 76 attach derived 766:772 arg2 antigens 757:764 T4 antigens 754:764 T4 antigens derived from sheep and mouse 754:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 3 76 attach derived 766:772 arg1 sheep 779:783 sheep 779:783 sheep 779:783 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 3 76 attach derived 766:772 arg1 mouse 789:793 mouse 789:793 mouse 789:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 2 77 theme 369-amino 342:350 arg1 sequence 362:369 the 369-amino acid-long sequence 338:369 the 369-amino acid-long sequence 338:369 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 0 78 theme structural 25:34 arg1 analysis 36:43 carbohydrate structural analysis 12:43 carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry 12:102 Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. 2592374 1 79 theme peptide 254:260 arg1 mapping 262:268 mass spectrometric peptide mapping 235:268 mass spectrometric peptide mapping 235:268 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 5 80 theme potential 921:929 arg1 sites 956:960 both potential Asn-linked glycosylation sites 916:960 both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) 916:988 Carbohydrate mapping by mass spectrometry was used to establish that both potential Asn-linked glycosylation sites in sCD4 (Asn271 and Asn300) have oligosaccharides attached. 2592374 2 81 theme translation 403:413 arg1 fidelity 391:398 the fidelity 387:398 the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends 387:480 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 3 82 theme high 607:610 arg1 chromatography 631:644 comparative high performance liquid chromatography 595:644 comparative high performance liquid chromatography 595:644 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 6 83 theme Structural 1022:1031 arg1 characterization 1033:1048 Structural characterization 1022:1048 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites 1022:1183 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 2592374 2 84 theme terminal 435:442 arg1 translation 403:413 translation 403:413 translation of the NH2 and COOH terminal 403:442 These studies corroborated 95% of the 369-amino acid-long sequence and established the fidelity of translation of the NH2 and COOH terminal including the absence of "ragged ends." 2592374 0 85 theme recombinant 50:60 arg1 receptor 74:81 a recombinant soluble CD4 receptor 48:81 a recombinant soluble CD4 receptor 48:81 Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. 2592374 7 86 theme anion-exchange 1510:1523 arg1 chromatography 1525:1538 high performance anion-exchange chromatography 1493:1538 high performance anion-exchange chromatography 1493:1538 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 7 87 theme high 1493:1496 arg1 chromatography 1525:1538 high performance anion-exchange chromatography 1493:1538 high performance anion-exchange chromatography 1493:1538 Minor carbohydrate components having three N-acetylneuraminic acid (NeuAc) groups and an additional hexose-hexosamine unit were detected by high performance anion-exchange chromatography. 2592374 3 88 theme liquid 624:629 arg1 chromatography 631:644 comparative high performance liquid chromatography 595:644 comparative high performance liquid chromatography 595:644 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 1 89 theme ovary 201:205 arg1 cells 207:211 Chinese hamster ovary cells 185:211 Chinese hamster ovary cells 185:211 The primary structure of a soluble form of the CD4 receptor (sCD4) expressed in Chinese hamster ovary cells has been confirmed by mass spectrometric peptide mapping and and tandem mass spectrometry. 2592374 3 90 dep spectrometry 578:589 arg1 shown 658:662 shown 658:662 shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse 658:793 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 3 90 dep spectrometry 578:589 arg1 mapping 646:652 mapping 646:652 mapping 646:652 The arrangement of the three disulfide bonds in recombinant sCD4 was also established by mass spectrometry and comparative high performance liquid chromatography mapping and shown to be identical to that expected from previous studies of intrachain disulfide bonding in T4 antigens derived from sheep and mouse. 2592374 6 91 theme heterogeneous 1103:1115 arg1 family 1117:1122 the heterogeneous family 1099:1122 the heterogeneous family of oligosaccharides at each of the specific attachment sites 1099:1183 Structural characterization by mass spectrometry and methylation analysis of the heterogeneous family of oligosaccharides at each of the specific attachment sites indicates that the major components of both families of oligosaccharides have the following biantennary structures: (Formula, see text) where m + n = 0-2, and x = 0,1. 36239522 1 0 theme molar 297:301 arg1 ratio 303:307 a molar ratio 295:307 a molar ratio of 4.2: 1 295:317 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 4 1 theme alcoholic 698:706 arg1 ALI 722:724 ALI 722:724 ALI 722:724 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 4 1 theme alcoholic 698:706 arg1 injury 714:719 alcoholic liver injury 698:719 alcoholic liver injury (ALI) 698:725 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 5 2 dep index 873:877 arg1 TNF-α 880:884 TNF-α 880:884 TNF-α 880:884 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 2 dep index 873:877 arg1 SOD 899:901 SOD 899:901 SOD 899:901 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 2 dep index 873:877 arg1 MDA 908:910 MDA 908:910 MDA 908:910 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 2 dep index 873:877 arg1 PGE2 893:896 PGE2 893:896 PGE2 893:896 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 2 dep index 873:877 arg1 IL-6 887:890 IL-6 887:890 IL-6 887:890 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 4 3 theme injury 714:719 arg1 models 734:739 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models 645:739 models 734:739 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 1 4 theme composition 245:255 arg1 weight 202:207 molecular weight 192:207 molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 192:317 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 0 5 theme liver 82:86 arg1 injury 88:93 liver injury 82:93 liver injury 82:93 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 0 6 from characterization 11:26 arg1 officinale 137:146 Dendrobium officinale 126:146 Dendrobium officinale 126:146 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 0 6 from characterization 11:26 arg1 mucosa 71:76 alcoholic gastric mucosa 53:76 alcoholic gastric mucosa 53:76 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 0 6 from characterization 11:26 arg1 injury 88:93 liver injury 82:93 liver injury 82:93 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 6 7 theme hepatocyte 1163:1172 arg1 necrosis 1174:1181 hepatocyte necrosis 1163:1181 hepatocyte necrosis 1163:1181 Histopathological results displayed that the DOP groups improved gastric epithelial defect and inflammatory cell redness caused by AGMI, and decreased vacuolization, hepatocyte necrosis and fibrosis caused by ALI. 36239522 3 8 theme In 457:458 arg1 data 466:469 In vitro data 457:469 In vitro data 457:469 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 8 9 theme therapeutic 1391:1401 arg1 reagent 1403:1409 a therapeutic reagent 1389:1409 a therapeutic reagent to attenuate alcohol gastric mucosal and liver injury 1389:1463 These results manifested that DOP may be a therapeutic reagent to attenuate alcohol gastric mucosal and liver injury. 36239522 8 9 theme therapeutic 1391:1401 arg1 DOP 1378:1380 DOP 1378:1380 DOP 1378:1380 These results manifested that DOP may be a therapeutic reagent to attenuate alcohol gastric mucosal and liver injury. 36239522 6 10 theme DOP 1042:1044 arg1 groups 1046:1051 the DOP groups 1038:1051 the DOP groups 1038:1051 Histopathological results displayed that the DOP groups improved gastric epithelial defect and inflammatory cell redness caused by AGMI, and decreased vacuolization, hepatocyte necrosis and fibrosis caused by ALI. 36239522 4 11 theme liver 708:712 arg1 ALI 722:724 ALI 722:724 ALI 722:724 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 4 11 theme liver 708:712 arg1 injury 714:719 alcoholic liver injury 698:719 alcoholic liver injury (ALI) 698:725 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 7 12 theme free 1287:1290 arg1 radicals 1292:1299 free radicals 1287:1299 free radicals 1287:1299 The results might be related to adjusting inflammatory factors, eliminating free radicals, and inhibiting lipid peroxidation capacities. 36239522 1 13 theme mannose 260:266 arg1 8.25 × 105 Da 212:224 8.25 × 105 Da 212:224 8.25 × 105 Da 212:224 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 1 13 theme mannose 260:266 arg1 composition 245:255 monosaccharide composition 230:255 monosaccharide composition 230:255 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 1 14 theme 4.2 312:314 arg1 ratio 303:307 a molar ratio 295:307 a molar ratio of 4.2: 1 295:317 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 4 15 theme DOP 818:820 arg1 abilities 805:813 the gastrotrophic and hepatoprotective abilities 766:813 the gastrotrophic and hepatoprotective abilities of DOP 766:820 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 3 16 theme IC50 490:493 arg1 2.762 mg/mL 602:612 2.762 mg/mL 602:612 2.762 mg/mL 602:612 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 3 16 theme IC50 490:493 arg1 values 495:500 the IC50 values 486:500 the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity 486:595 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 5 17 theme mucosal 865:871 arg1 index 873:877 gastric mucosal index 857:877 gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) 857:911 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 0 18 theme polysaccharide 106:119 arg1 characterization 11:26 Structural characterization 0:26 Structural characterization 0:26 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 0 18 theme polysaccharide 106:119 arg1 effect 43:48 preventive effect 32:48 preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale 32:146 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 6 19 theme Histopathological 997:1013 arg1 results 1015:1021 Histopathological results 997:1021 Histopathological results 997:1021 Histopathological results displayed that the DOP groups improved gastric epithelial defect and inflammatory cell redness caused by AGMI, and decreased vacuolization, hepatocyte necrosis and fibrosis caused by ALI. 36239522 4 20 theme gastrotrophic 770:782 arg1 abilities 805:813 the gastrotrophic and hepatoprotective abilities 766:813 the gastrotrophic and hepatoprotective abilities of DOP 766:820 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 5 21 theme gastric 857:863 arg1 index 873:877 gastric mucosal index 857:877 gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) 857:911 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 0 22 theme novel 100:104 arg1 polysaccharide 106:119 a novel polysaccharide 98:119 a novel polysaccharide from Dendrobium officinale 98:146 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 2 23 theme DOP 430:432 arg1 effect 375:380 The preventive effect 360:380 The preventive effect on alcoholic gastric mucosa and liver injury of DOP 360:432 The preventive effect on alcoholic gastric mucosa and liver injury of DOP was also investigated. 36239522 1 24 theme 8.25 × 105 Da 212:224 arg1 weight 202:207 molecular weight 192:207 molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 192:317 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 1 25 attach isolated 323:330 arg1 officinale 348:357 Dendrobium officinale 337:357 Dendrobium officinale 337:357 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 1 25 attach isolated 323:330 arg2 DOP 182:184 DOP 182:184 DOP 182:184 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 1 25 attach isolated 323:330 arg2 polysaccharide 166:179 a polysaccharide 164:179 a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 164:317 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 0 26 from effect 43:48 arg1 officinale 137:146 Dendrobium officinale 126:146 Dendrobium officinale 126:146 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 0 26 from effect 43:48 arg1 mucosa 71:76 alcoholic gastric mucosa 53:76 alcoholic gastric mucosa 53:76 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 0 26 from effect 43:48 arg1 injury 88:93 liver injury 82:93 liver injury 82:93 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 4 27 theme hepatoprotective 788:803 arg1 abilities 805:813 the gastrotrophic and hepatoprotective abilities 766:813 the gastrotrophic and hepatoprotective abilities of DOP 766:820 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 4 28 used used 746:749 arg2 models 734:739 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models 645:739 models 734:739 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 0 29 theme Structural 0:9 arg1 characterization 11:26 Structural characterization 0:26 Structural characterization 0:26 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 7 30 theme lipid 1317:1321 arg1 capacities 1336:1345 lipid peroxidation capacities 1317:1345 lipid peroxidation capacities 1317:1345 The results might be related to adjusting inflammatory factors, eliminating free radicals, and inhibiting lipid peroxidation capacities. 36239522 3 31 dep In 457:458 arg1 vitro 460:464 vitro 460:464 vitro 460:464 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 0 32 theme preventive 32:41 arg1 effect 43:48 preventive effect 32:48 preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale 32:146 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 0 33 theme Dendrobium 126:135 arg1 officinale 137:146 Dendrobium officinale 126:146 Dendrobium officinale 126:146 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 4 34 theme alcoholic 654:662 arg1 AGMI 688:691 AGMI 688:691 AGMI 688:691 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 4 34 theme alcoholic 654:662 arg1 injury 680:685 alcoholic gastric mucosal injury 654:685 alcoholic gastric mucosal injury (AGMI) 654:692 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 2 35 theme gastric 395:401 arg1 mucosa 403:408 alcoholic gastric mucosa 385:408 alcoholic gastric mucosa 385:408 The preventive effect on alcoholic gastric mucosa and liver injury of DOP was also investigated. 36239522 3 36 theme capacity 588:595 arg1 2.762 mg/mL 602:612 2.762 mg/mL 602:612 2.762 mg/mL 602:612 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 3 36 theme capacity 588:595 arg1 values 495:500 the IC50 values 486:500 the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity 486:595 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 5 37 theme DOP 847:849 arg1 administration 829:842 administration 829:842 administration of DOP 829:849 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 2 38 theme preventive 364:373 arg1 effect 375:380 The preventive effect 360:380 The preventive effect on alcoholic gastric mucosa and liver injury of DOP 360:432 The preventive effect on alcoholic gastric mucosa and liver injury of DOP was also investigated. 36239522 1 39 from ratio 303:307 arg1 8.25 × 105 Da 212:224 8.25 × 105 Da 212:224 8.25 × 105 Da 212:224 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 1 39 from ratio 303:307 arg1 composition 245:255 monosaccharide composition 230:255 monosaccharide composition 230:255 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 1 39 from ratio 303:307 arg1 weight 202:207 molecular weight 192:207 molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 192:317 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 1 40 theme glucose 278:284 arg1 8.25 × 105 Da 212:224 8.25 × 105 Da 212:224 8.25 × 105 Da 212:224 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 1 40 theme glucose 278:284 arg1 composition 245:255 monosaccharide composition 230:255 monosaccharide composition 230:255 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 3 41 dep ability 561:567 arg1 1-diphenyl-2-picrylhydrazy 508:533 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability 505:567 1-diphenyl-2-picrylhydrazy 508:533 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 3 42 theme DPPH 536:539 arg1 ability 561:567 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability 505:567 ability 561:567 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 6 43 theme epithelial 1070:1079 arg1 defect 1081:1086 gastric epithelial defect 1062:1086 gastric epithelial defect 1062:1086 Histopathological results displayed that the DOP groups improved gastric epithelial defect and inflammatory cell redness caused by AGMI, and decreased vacuolization, hepatocyte necrosis and fibrosis caused by ALI. 36239522 1 44 theme molecular 192:200 arg1 weight 202:207 molecular weight 192:207 molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 192:317 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 1 45 theme Dendrobium 337:346 arg1 officinale 348:357 Dendrobium officinale 337:357 Dendrobium officinale 337:357 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 2 46 theme alcoholic 385:393 arg1 mucosa 403:408 alcoholic gastric mucosa 385:408 alcoholic gastric mucosa 385:408 The preventive effect on alcoholic gastric mucosa and liver injury of DOP was also investigated. 36239522 7 47 theme inflammatory 1253:1264 arg1 factors 1266:1272 inflammatory factors 1253:1272 inflammatory factors 1253:1272 The results might be related to adjusting inflammatory factors, eliminating free radicals, and inhibiting lipid peroxidation capacities. 36239522 0 48 theme gastric 63:69 arg1 mucosa 71:76 alcoholic gastric mucosa 53:76 alcoholic gastric mucosa 53:76 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 3 49 theme chelating 578:586 arg1 capacity 588:595 Fe2+ chelating capacity 573:595 Fe2+ chelating capacity 573:595 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 5 50 theme hepatic 917:923 arg1 SOD 947:949 SOD 947:949 SOD 947:949 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 50 theme hepatic 917:923 arg1 MDA 955:957 MDA 955:957 MDA 955:957 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 50 theme hepatic 917:923 arg1 ALT 937:939 ALT 937:939 ALT 937:939 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 50 theme hepatic 917:923 arg1 AST 942:944 AST 942:944 AST 942:944 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 50 theme hepatic 917:923 arg1 indicators 925:934 hepatic indicators 917:934 hepatic indicators (ALT, AST, SOD and MDA) 917:958 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 1 51 from weight 202:207 arg1 ratio 303:307 a molar ratio 295:307 a molar ratio of 4.2: 1 295:317 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 4 52 theme gastric 664:670 arg1 AGMI 688:691 AGMI 688:691 AGMI 688:691 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 4 52 theme gastric 664:670 arg1 injury 680:685 alcoholic gastric mucosal injury 654:685 alcoholic gastric mucosal injury (AGMI) 654:692 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 0 53 theme alcoholic 53:61 arg1 mucosa 71:76 alcoholic gastric mucosa 53:76 alcoholic gastric mucosa 53:76 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 1 54 dep 4.2 312:314 arg1 1 317:317 1 317:317 1 317:317 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 8 55 theme liver 1452:1456 arg1 injury 1458:1463 alcohol gastric mucosal and liver injury 1424:1463 injury 1458:1463 These results manifested that DOP may be a therapeutic reagent to attenuate alcohol gastric mucosal and liver injury. 36239522 6 56 theme cell 1105:1108 arg1 redness 1110:1116 inflammatory cell redness 1092:1116 inflammatory cell redness 1092:1116 Histopathological results displayed that the DOP groups improved gastric epithelial defect and inflammatory cell redness caused by AGMI, and decreased vacuolization, hepatocyte necrosis and fibrosis caused by ALI. 36239522 3 57 theme Fe2+ 573:576 arg1 capacity 588:595 Fe2+ chelating capacity 573:595 Fe2+ chelating capacity 573:595 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 4 58 theme animal 727:732 arg1 models 734:739 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models 645:739 models 734:739 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 6 59 theme inflammatory 1092:1103 arg1 redness 1110:1116 inflammatory cell redness 1092:1116 inflammatory cell redness 1092:1116 Histopathological results displayed that the DOP groups improved gastric epithelial defect and inflammatory cell redness caused by AGMI, and decreased vacuolization, hepatocyte necrosis and fibrosis caused by ALI. 36239522 3 60 theme ability 561:567 arg1 2.762 mg/mL 602:612 2.762 mg/mL 602:612 2.762 mg/mL 602:612 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 3 60 theme ability 561:567 arg1 values 495:500 the IC50 values 486:500 the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity 486:595 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 4 61 theme injury 680:685 arg1 models 734:739 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models 645:739 models 734:739 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 1 62 with polysaccharide 166:179 arg1 weight 202:207 molecular weight 192:207 molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 192:317 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36239522 6 63 theme gastric 1062:1068 arg1 defect 1081:1086 gastric epithelial defect 1062:1086 gastric epithelial defect 1062:1086 Histopathological results displayed that the DOP groups improved gastric epithelial defect and inflammatory cell redness caused by AGMI, and decreased vacuolization, hepatocyte necrosis and fibrosis caused by ALI. 36239522 4 64 theme mucosal 672:678 arg1 AGMI 688:691 AGMI 688:691 AGMI 688:691 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 4 64 theme mucosal 672:678 arg1 injury 680:685 alcoholic gastric mucosal injury 654:685 alcoholic gastric mucosal injury (AGMI) 654:692 Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. 36239522 0 65 from officinale 137:146 arg1 characterization 11:26 Structural characterization 0:26 Structural characterization 0:26 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 0 65 from officinale 137:146 arg1 effect 43:48 preventive effect 32:48 preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale 32:146 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 0 65 from officinale 137:146 arg1 polysaccharide 106:119 a novel polysaccharide 98:119 a novel polysaccharide from Dendrobium officinale 98:146 Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale. 36239522 7 66 theme peroxidation 1323:1334 arg1 capacities 1336:1345 lipid peroxidation capacities 1317:1345 lipid peroxidation capacities 1317:1345 The results might be related to adjusting inflammatory factors, eliminating free radicals, and inhibiting lipid peroxidation capacities. 36239522 3 67 theme radical 542:548 arg1 ability 561:567 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability 505:567 ability 561:567 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 5 68 dep indicators 925:934 arg1 SOD 947:949 SOD 947:949 SOD 947:949 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 68 dep indicators 925:934 arg1 AST 942:944 AST 942:944 AST 942:944 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 68 dep indicators 925:934 arg1 ALT 937:939 ALT 937:939 ALT 937:939 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 68 dep indicators 925:934 arg1 indicators 925:934 hepatic indicators 917:934 hepatic indicators (ALT, AST, SOD and MDA) 917:958 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 5 68 dep indicators 925:934 arg1 MDA 955:957 MDA 955:957 MDA 955:957 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 2 69 theme liver 414:418 arg1 injury 420:425 liver injury 414:425 liver injury 414:425 The preventive effect on alcoholic gastric mucosa and liver injury of DOP was also investigated. 36239522 5 70 theme non-DOP 981:987 arg1 groups 989:994 non-DOP groups 981:994 non-DOP groups 981:994 After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. 36239522 3 71 theme scavenging 550:559 arg1 ability 561:567 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability 505:567 ability 561:567 In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. 36239522 2 72 from effect 375:380 arg1 mucosa 403:408 alcoholic gastric mucosa 385:408 alcoholic gastric mucosa 385:408 The preventive effect on alcoholic gastric mucosa and liver injury of DOP was also investigated. 36239522 2 72 from effect 375:380 arg1 injury 420:425 liver injury 414:425 liver injury 414:425 The preventive effect on alcoholic gastric mucosa and liver injury of DOP was also investigated. 36239522 1 73 theme monosaccharide 230:243 arg1 composition 245:255 monosaccharide composition 230:255 monosaccharide composition 230:255 In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. 36098859 3 0 theme Modified 309:316 arg1 pectin 329:334 Modified sugar beet pectin 309:334 Modified sugar beet pectin 309:334 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 3 0 theme Modified 309:316 arg1 polymer 362:368 a natural polymer 352:368 a natural polymer with pronounced surface activity 352:401 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 8 1 theme shell 1140:1144 arg1 content 1146:1152 the shell content 1136:1152 the shell content 1136:1152 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 9 2 theme cross-linked 1182:1193 arg1 220-240 nm 1205:1214 220-240 nm 1205:1214 220-240 nm 1205:1214 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 9 2 theme cross-linked 1182:1193 arg1 capsules 1195:1202 The obtained submicrometer cross-linked capsules 1155:1202 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties 1155:1252 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 1 3 theme liposomal 145:153 arg1 suspensions 155:165 diluted liposomal suspensions 137:165 diluted liposomal suspensions 137:165 The Ugi four-component condensation in diluted liposomal suspensions was used to prepare pectin-based submicron capsules. 36098859 10 4 contain have 1322:1325 arg2 potential 1335:1343 a great potential 1327:1343 a great potential as sustained drug delivery systems for different administration routes 1327:1414 Thus, the proposed carriers have a great potential as sustained drug delivery systems for different administration routes. 36098859 10 4 contain have 1322:1325 arg1 carriers 1313:1320 the proposed carriers 1300:1320 the proposed carriers 1300:1320 Thus, the proposed carriers have a great potential as sustained drug delivery systems for different administration routes. 36098859 3 5 theme sugar 318:322 arg1 pectin 329:334 Modified sugar beet pectin 309:334 Modified sugar beet pectin 309:334 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 3 5 theme sugar 318:322 arg1 polymer 362:368 a natural polymer 352:368 a natural polymer with pronounced surface activity 352:401 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 4 6 theme suitable 495:502 arg1 conditions 504:513 suitable conditions 495:513 suitable conditions 495:513 At first, liposomal composition was optimized in order to select suitable conditions for capsule formation. 36098859 9 7 theme colloidal 1233:1241 arg1 properties 1243:1252 controlled colloidal properties 1222:1252 controlled colloidal properties 1222:1252 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 7 8 theme various 877:883 arg1 parameters 896:905 various processing parameters 877:905 various processing parameters (concentration, cross-linking components, the density of linkage) 877:971 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 8 9 from dependence 1122:1131 arg1 content 1146:1152 the shell content 1136:1152 the shell content 1136:1152 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 0 10 theme beet 85:88 arg1 pectin 90:95 sugar beet pectin 79:95 sugar beet pectin 79:95 Application of the Ugi reaction for preparation of submicron capsules based on sugar beet pectin. 36098859 9 11 theme controlled 1222:1231 arg1 properties 1243:1252 controlled colloidal properties 1222:1252 controlled colloidal properties 1222:1252 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 7 12 theme linkage 964:970 arg1 density 953:959 the density 949:959 the density of linkage 949:970 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 7 12 theme linkage 964:970 arg1 concentration 908:920 concentration 908:920 concentration 908:920 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 7 13 theme processing 885:894 arg1 parameters 896:905 various processing parameters 877:905 various processing parameters (concentration, cross-linking components, the density of linkage) 877:971 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 0 14 theme sugar 79:83 arg1 pectin 90:95 sugar beet pectin 79:95 sugar beet pectin 79:95 Application of the Ugi reaction for preparation of submicron capsules based on sugar beet pectin. 36098859 7 15 with particles 833:841 arg1 core 858:861 liposomal core 848:861 liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage) 848:971 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 10 16 theme drug 1358:1361 arg1 systems 1372:1378 sustained drug delivery systems 1348:1378 sustained drug delivery systems for different administration routes 1348:1414 Thus, the proposed carriers have a great potential as sustained drug delivery systems for different administration routes. 36098859 5 17 theme modified 584:591 arg1 scaffold 611:618 modified sugar beet pectin scaffold 584:618 modified sugar beet pectin scaffold 584:618 Then, the wide set of capsules constructed on modified sugar beet pectin scaffold has been synthesized. 36098859 6 18 theme degree 693:698 arg1 diversity 722:730 possible chemical diversity 704:730 possible chemical diversity of the modified surface 704:754 The choice was determined by level of substitution degree and possible chemical diversity of the modified surface. 36098859 6 18 theme degree 693:698 arg1 level 671:675 level 671:675 level of substitution degree 671:698 The choice was determined by level of substitution degree and possible chemical diversity of the modified surface. 36098859 5 19 theme beet 599:602 arg1 scaffold 611:618 modified sugar beet pectin scaffold 584:618 modified sugar beet pectin scaffold 584:618 Then, the wide set of capsules constructed on modified sugar beet pectin scaffold has been synthesized. 36098859 5 20 theme sugar 593:597 arg1 scaffold 611:618 modified sugar beet pectin scaffold 584:618 modified sugar beet pectin scaffold 584:618 Then, the wide set of capsules constructed on modified sugar beet pectin scaffold has been synthesized. 36098859 6 21 theme substitution 680:691 arg1 degree 693:698 substitution degree 680:698 substitution degree 680:698 The choice was determined by level of substitution degree and possible chemical diversity of the modified surface. 36098859 5 22 theme pectin 604:609 arg1 scaffold 611:618 modified sugar beet pectin scaffold 584:618 modified sugar beet pectin scaffold 584:618 Then, the wide set of capsules constructed on modified sugar beet pectin scaffold has been synthesized. 36098859 5 23 theme wide 548:551 arg1 capsules 560:567 capsules 560:567 capsules constructed on modified sugar beet pectin scaffold 560:618 Then, the wide set of capsules constructed on modified sugar beet pectin scaffold has been synthesized. 36098859 5 23 theme wide 548:551 arg1 set 553:555 the wide set 544:555 the wide set of capsules constructed on modified sugar beet pectin scaffold 544:618 Then, the wide set of capsules constructed on modified sugar beet pectin scaffold has been synthesized. 36098859 7 24 theme liposomal 848:856 arg1 core 858:861 liposomal core 848:861 liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage) 848:971 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 1 25 from condensation 121:132 arg1 suspensions 155:165 diluted liposomal suspensions 137:165 diluted liposomal suspensions 137:165 The Ugi four-component condensation in diluted liposomal suspensions was used to prepare pectin-based submicron capsules. 36098859 2 26 used used 259:262 arg2 aldehydes 245:253 aldehydes 245:253 aldehydes 245:253 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 2 26 used used 259:262 arg2 isocyanides 229:239 isocyanides 229:239 isocyanides 229:239 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 2 26 used used 259:262 arg2 set 222:224 A set 220:224 A set of isocyanides and aldehydes 220:253 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 3 27 theme pronounced 375:384 arg1 activity 394:401 pronounced surface activity 375:401 pronounced surface activity 375:401 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 7 28 dep parameters 896:905 arg1 density 953:959 the density 949:959 the density of linkage 949:970 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 7 28 dep parameters 896:905 arg1 concentration 908:920 concentration 908:920 concentration 908:920 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 7 28 dep parameters 896:905 arg1 components 937:946 cross-linking components 923:946 cross-linking components 923:946 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 2 29 theme shells 301:306 arg1 synthesis 280:288 the synthesis 276:288 the synthesis of capsule shells 276:306 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 3 30 theme capsule 415:421 arg1 shell 423:427 a capsule shell 413:427 a capsule shell 413:427 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 0 31 theme Ugi 19:21 arg1 reaction 23:30 the Ugi reaction 15:30 the Ugi reaction 15:30 Application of the Ugi reaction for preparation of submicron capsules based on sugar beet pectin. 36098859 1 32 used used 171:174 arg2 condensation 121:132 The Ugi four-component condensation 98:132 The Ugi four-component condensation in diluted liposomal suspensions 98:165 The Ugi four-component condensation in diluted liposomal suspensions was used to prepare pectin-based submicron capsules. 36098859 8 33 theme particles 1086:1094 arg1 morphology 1034:1043 morphology 1034:1043 morphology 1034:1043 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 8 33 theme particles 1086:1094 arg1 stability 1046:1054 stability 1046:1054 stability 1046:1054 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 8 33 theme particles 1086:1094 arg1 size 1006:1009 average size 998:1009 average size 998:1009 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 8 33 theme particles 1086:1094 arg1 index 1027:1031 polydispersity index 1012:1031 polydispersity index 1012:1031 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 8 33 theme particles 1086:1094 arg1 cytotoxicity 1061:1072 cytotoxicity 1061:1072 cytotoxicity 1061:1072 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 8 33 theme particles 1086:1094 arg1 structure 987:995 chemical structure 978:995 chemical structure 978:995 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 5 34 theme capsules 560:567 arg1 capsules 560:567 capsules 560:567 capsules constructed on modified sugar beet pectin scaffold 560:618 Then, the wide set of capsules constructed on modified sugar beet pectin scaffold has been synthesized. 36098859 5 34 theme capsules 560:567 arg1 set 553:555 the wide set 544:555 the wide set of capsules constructed on modified sugar beet pectin scaffold 544:618 Then, the wide set of capsules constructed on modified sugar beet pectin scaffold has been synthesized. 36098859 2 35 theme capsule 293:299 arg1 shells 301:306 capsule shells 293:306 capsule shells 293:306 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 8 36 theme polydispersity 1012:1025 arg1 index 1027:1031 polydispersity index 1012:1031 polydispersity index 1012:1031 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 1 37 theme pectin-based 187:198 arg1 capsules 210:217 pectin-based submicron capsules 187:217 pectin-based submicron capsules 187:217 The Ugi four-component condensation in diluted liposomal suspensions was used to prepare pectin-based submicron capsules. 36098859 3 38 with polymer 362:368 arg1 activity 394:401 pronounced surface activity 375:401 pronounced surface activity 375:401 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 7 39 theme products 786:793 arg1 characterization 766:781 Detailed characterization 757:781 Detailed characterization of products 757:793 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 8 40 theme obtained 1077:1084 arg1 particles 1086:1094 obtained particles 1077:1094 obtained particles 1077:1094 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 1 41 theme submicron 200:208 arg1 capsules 210:217 pectin-based submicron capsules 187:217 pectin-based submicron capsules 187:217 The Ugi four-component condensation in diluted liposomal suspensions was used to prepare pectin-based submicron capsules. 36098859 10 42 theme proposed 1304:1311 arg1 carriers 1313:1320 the proposed carriers 1300:1320 the proposed carriers 1300:1320 Thus, the proposed carriers have a great potential as sustained drug delivery systems for different administration routes. 36098859 0 43 theme capsules 61:68 arg1 preparation 36:46 preparation 36:46 preparation of submicron capsules 36:68 Application of the Ugi reaction for preparation of submicron capsules based on sugar beet pectin. 36098859 9 44 theme high 1261:1264 arg1 stability 1266:1274 high stability 1261:1274 high stability 1261:1274 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 2 45 theme isocyanides 229:239 arg1 aldehydes 245:253 aldehydes 245:253 aldehydes 245:253 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 2 45 theme isocyanides 229:239 arg1 isocyanides 229:239 isocyanides 229:239 isocyanides 229:239 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 2 45 theme isocyanides 229:239 arg1 set 222:224 A set 220:224 A set of isocyanides and aldehydes 220:253 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 7 46 theme polysaccharide 818:831 arg1 particles 833:841 polysaccharide particles 818:841 polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage) 818:971 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 0 47 theme reaction 23:30 arg1 Application 0:10 Application 0:10 Application of the Ugi reaction for preparation of submicron capsules 0:68 Application of the Ugi reaction for preparation of submicron capsules based on sugar beet pectin. 36098859 8 48 theme average 998:1004 arg1 size 1006:1009 average size 998:1009 average size 998:1009 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 4 49 theme liposomal 440:448 arg1 composition 450:460 liposomal composition 440:460 liposomal composition 440:460 At first, liposomal composition was optimized in order to select suitable conditions for capsule formation. 36098859 3 50 theme natural 354:360 arg1 pectin 329:334 Modified sugar beet pectin 309:334 Modified sugar beet pectin 309:334 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 3 50 theme natural 354:360 arg1 polymer 362:368 a natural polymer 352:368 a natural polymer with pronounced surface activity 352:401 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 6 51 theme surface 748:754 arg1 diversity 722:730 possible chemical diversity 704:730 possible chemical diversity of the modified surface 704:754 The choice was determined by level of substitution degree and possible chemical diversity of the modified surface. 36098859 6 51 theme surface 748:754 arg1 level 671:675 level 671:675 level of substitution degree 671:698 The choice was determined by level of substitution degree and possible chemical diversity of the modified surface. 36098859 7 52 theme Detailed 757:764 arg1 characterization 766:781 Detailed characterization 757:781 Detailed characterization of products 757:793 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 3 53 theme surface 386:392 arg1 activity 394:401 pronounced surface activity 375:401 pronounced surface activity 375:401 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 9 54 link cross-linked 1182:1193 arg1 220-240 nm 1205:1214 220-240 nm 1205:1214 220-240 nm 1205:1214 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 9 54 link cross-linked 1182:1193 arg1 capsules 1195:1202 The obtained submicrometer cross-linked capsules 1155:1202 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties 1155:1252 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 6 55 theme modified 739:746 arg1 surface 748:754 the modified surface 735:754 the modified surface 735:754 The choice was determined by level of substitution degree and possible chemical diversity of the modified surface. 36098859 9 56 with capsules 1195:1202 arg1 properties 1243:1252 controlled colloidal properties 1222:1252 controlled colloidal properties 1222:1252 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 9 57 theme low 1280:1282 arg1 toxicity 1284:1291 low toxicity 1280:1291 low toxicity 1280:1291 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 10 58 theme sustained 1348:1356 arg1 systems 1372:1378 sustained drug delivery systems 1348:1378 sustained drug delivery systems for different administration routes 1348:1414 Thus, the proposed carriers have a great potential as sustained drug delivery systems for different administration routes. 36098859 1 59 theme Ugi 102:104 arg1 condensation 121:132 The Ugi four-component condensation 98:132 The Ugi four-component condensation in diluted liposomal suspensions 98:165 The Ugi four-component condensation in diluted liposomal suspensions was used to prepare pectin-based submicron capsules. 36098859 7 60 theme cross-linking 923:935 arg1 concentration 908:920 concentration 908:920 concentration 908:920 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 7 60 theme cross-linking 923:935 arg1 components 937:946 cross-linking components 923:946 cross-linking components 923:946 Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). 36098859 4 61 theme capsule 519:525 arg1 formation 527:535 capsule formation 519:535 capsule formation 519:535 At first, liposomal composition was optimized in order to select suitable conditions for capsule formation. 36098859 8 62 theme chemical 978:985 arg1 structure 987:995 chemical structure 978:995 chemical structure 978:995 The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. 36098859 1 63 theme four-component 106:119 arg1 condensation 121:132 The Ugi four-component condensation 98:132 The Ugi four-component condensation in diluted liposomal suspensions 98:165 The Ugi four-component condensation in diluted liposomal suspensions was used to prepare pectin-based submicron capsules. 36098859 9 64 theme submicrometer 1168:1180 arg1 220-240 nm 1205:1214 220-240 nm 1205:1214 220-240 nm 1205:1214 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 9 64 theme submicrometer 1168:1180 arg1 capsules 1195:1202 The obtained submicrometer cross-linked capsules 1155:1202 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties 1155:1252 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 9 65 theme obtained 1159:1166 arg1 220-240 nm 1205:1214 220-240 nm 1205:1214 220-240 nm 1205:1214 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 9 65 theme obtained 1159:1166 arg1 capsules 1195:1202 The obtained submicrometer cross-linked capsules 1155:1202 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties 1155:1252 The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. 36098859 10 66 theme delivery 1363:1370 arg1 systems 1372:1378 sustained drug delivery systems 1348:1378 sustained drug delivery systems for different administration routes 1348:1414 Thus, the proposed carriers have a great potential as sustained drug delivery systems for different administration routes. 36098859 10 67 theme administration 1394:1407 arg1 routes 1409:1414 different administration routes 1384:1414 different administration routes 1384:1414 Thus, the proposed carriers have a great potential as sustained drug delivery systems for different administration routes. 36098859 10 68 theme great 1329:1333 arg1 potential 1335:1343 a great potential 1327:1343 a great potential as sustained drug delivery systems for different administration routes 1327:1414 Thus, the proposed carriers have a great potential as sustained drug delivery systems for different administration routes. 36098859 3 69 theme beet 324:327 arg1 pectin 329:334 Modified sugar beet pectin 309:334 Modified sugar beet pectin 309:334 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 3 69 theme beet 324:327 arg1 polymer 362:368 a natural polymer 352:368 a natural polymer with pronounced surface activity 352:401 Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. 36098859 10 70 theme different 1384:1392 arg1 routes 1409:1414 different administration routes 1384:1414 different administration routes 1384:1414 Thus, the proposed carriers have a great potential as sustained drug delivery systems for different administration routes. 36098859 2 71 theme aldehydes 245:253 arg1 aldehydes 245:253 aldehydes 245:253 aldehydes 245:253 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 2 71 theme aldehydes 245:253 arg1 isocyanides 229:239 isocyanides 229:239 isocyanides 229:239 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 2 71 theme aldehydes 245:253 arg1 set 222:224 A set 220:224 A set of isocyanides and aldehydes 220:253 A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. 36098859 6 72 theme chemical 713:720 arg1 diversity 722:730 possible chemical diversity 704:730 possible chemical diversity of the modified surface 704:754 The choice was determined by level of substitution degree and possible chemical diversity of the modified surface. 36098859 0 73 theme submicron 51:59 arg1 capsules 61:68 submicron capsules 51:68 submicron capsules 51:68 Application of the Ugi reaction for preparation of submicron capsules based on sugar beet pectin. 36098859 6 74 theme possible 704:711 arg1 diversity 722:730 possible chemical diversity 704:730 possible chemical diversity of the modified surface 704:754 The choice was determined by level of substitution degree and possible chemical diversity of the modified surface. 36098859 1 75 theme diluted 137:143 arg1 suspensions 155:165 diluted liposomal suspensions 137:165 diluted liposomal suspensions 137:165 The Ugi four-component condensation in diluted liposomal suspensions was used to prepare pectin-based submicron capsules. 35333306 6 0 theme stark 1013:1017 arg1 contrast 1019:1026 stark contrast 1013:1026 stark contrast to S. cerevisiae 1013:1043 Unexpectedly, and in stark contrast to S. cerevisiae, loss of Anp1, Mnn10, or Mnn11, which together synthesize most of the backbone, have no obvious deleterious phenotypes. 35333306 2 1 theme outer 342:346 arg1 chain 348:352 The asparagine (N)-linked mannose outer chain 308:352 The asparagine (N)-linked mannose outer chain of these glycoproteins 308:375 The asparagine (N)-linked mannose outer chain of these glycoproteins is produced by Golgi mannosyltransferases (MTases). 35333306 1 2 theme host 258:261 arg1 recognition 263:273 host recognition 258:273 host recognition 258:273 Candida albicans cell wall glycoproteins, and in particular their mannose-rich glycans, are important for maintaining cellular integrity as well as host recognition, adhesion, and immunomodulation. 35333306 0 3 link N-linked 25:32 arg1 glycan 46:51 The Mnn10/Anp1-dependent N-linked outer chain glycan 0:51 The Mnn10/Anp1-dependent N-linked outer chain glycan 0:51 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 0 3 link N-linked 25:32 arg1 dispensable 56:66 dispensable 56:66 dispensable 56:66 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 4 4 theme mannose 761:767 arg1 backbone 781:788 the α1,6 mannose outer chain backbone 752:788 the α1,6 mannose outer chain backbone 752:788 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 6 5 theme obvious 1133:1139 arg1 phenotypes 1153:1162 no obvious deleterious phenotypes 1130:1162 no obvious deleterious phenotypes 1130:1162 Unexpectedly, and in stark contrast to S. cerevisiae, loss of Anp1, Mnn10, or Mnn11, which together synthesize most of the backbone, have no obvious deleterious phenotypes. 35333306 1 6 theme mannose-rich 176:187 arg1 glycans 189:195 their mannose-rich glycans 170:195 their mannose-rich glycans 170:195 Candida albicans cell wall glycoproteins, and in particular their mannose-rich glycans, are important for maintaining cellular integrity as well as host recognition, adhesion, and immunomodulation. 35333306 4 7 theme chain 775:779 arg1 backbone 781:788 the α1,6 mannose outer chain backbone 752:788 the α1,6 mannose outer chain backbone 752:788 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 6 8 theme Mnn10 1060:1064 arg1 loss 1046:1049 loss 1046:1049 loss 1046:1049 Unexpectedly, and in stark contrast to S. cerevisiae, loss of Anp1, Mnn10, or Mnn11, which together synthesize most of the backbone, have no obvious deleterious phenotypes. 35333306 5 9 theme albicans 799:806 arg1 och1Δ/Δ 808:814 Candida albicans och1Δ/Δ 791:814 Candida albicans och1Δ/Δ 791:814 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 6 10 theme Anp1 1054:1057 arg1 loss 1046:1049 loss 1046:1049 loss 1046:1049 Unexpectedly, and in stark contrast to S. cerevisiae, loss of Anp1, Mnn10, or Mnn11, which together synthesize most of the backbone, have no obvious deleterious phenotypes. 35333306 5 11 theme earliest 856:863 arg1 steps 865:869 the earliest steps 852:869 the earliest steps of backbone synthesis 852:891 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 3 12 theme α1,6-linked 485:495 arg1 mannoses 497:504 ∼50 α1,6-linked mannoses 481:504 ∼50 α1,6-linked mannoses 481:504 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 1 13 theme cell 127:130 arg1 glycoproteins 137:149 Candida albicans cell wall glycoproteins 110:149 Candida albicans cell wall glycoproteins 110:149 Candida albicans cell wall glycoproteins, and in particular their mannose-rich glycans, are important for maintaining cellular integrity as well as host recognition, adhesion, and immunomodulation. 35333306 9 14 theme wall 1613:1616 arg1 integrity 1618:1626 cell wall integrity 1608:1626 cell wall integrity 1608:1626 This hypo-mannosylation did not elicit increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches. 35333306 3 15 theme mannoses 561:568 arg1 addition 536:543 addition 536:543 addition of ∼150 or more mannoses in other linkages 536:586 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 8 16 gly glycoproteins 1403:1415 arg1 glycoproteins 1403:1415 glycoproteins 1403:1415 glycoproteins with severely truncated N-glycan chains 1403:1455 Analyses of secreted glycosylation reporters demonstrated that anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains accumulate glycoproteins with severely truncated N-glycan chains. 35333306 5 17 theme growth 973:978 arg1 phenotypes 980:989 severe cell wall and growth phenotypes 952:989 phenotypes 980:989 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 10 18 theme N-linked 1727:1734 arg1 levels 1743:1748 N-linked mannan levels 1727:1748 N-linked mannan levels 1727:1748 Thus, C. albicans has evolved an alternate mechanism to adapt to cell wall weakness when N-linked mannan levels are reduced. 35333306 1 19 from glycans 189:195 arg1 particular 159:168 particular 159:168 particular 159:168 Candida albicans cell wall glycoproteins, and in particular their mannose-rich glycans, are important for maintaining cellular integrity as well as host recognition, adhesion, and immunomodulation. 35333306 8 20 theme mnn11Δ/Δ 1375:1382 arg1 strains 1384:1390 anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains 1352:1390 strains 1384:1390 Analyses of secreted glycosylation reporters demonstrated that anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains accumulate glycoproteins with severely truncated N-glycan chains. 35333306 7 21 theme drug 1223:1226 arg1 sensitivities 1228:1240 drug sensitivities 1223:1240 drug sensitivities 1223:1240 These mutants were unaffected in cell morphology, growth, drug sensitivities, hyphal formation, and macrophage recognition. 35333306 3 22 theme other 573:577 arg1 linkages 579:586 other linkages 573:586 other linkages 573:586 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 0 23 theme albicans 80:87 arg1 integrity 99:107 Candida albicans cell wall integrity 72:107 Candida albicans cell wall integrity 72:107 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 0 24 theme wall 94:97 arg1 integrity 99:107 Candida albicans cell wall integrity 72:107 Candida albicans cell wall integrity 72:107 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 5 25 theme synthesis 883:891 arg1 steps 865:869 the earliest steps 852:869 the earliest steps of backbone synthesis 852:891 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 8 26 theme truncated 1431:1439 arg1 chains 1450:1455 severely truncated N-glycan chains 1422:1455 severely truncated N-glycan chains 1422:1455 Analyses of secreted glycosylation reporters demonstrated that anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains accumulate glycoproteins with severely truncated N-glycan chains. 35333306 4 27 dep albicans 634:641 arg1 VAN1 655:658 VAN1 655:658 VAN1 655:658 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 4 27 dep albicans 634:641 arg1 MNN11 678:682 MNN11 678:682 MNN11 678:682 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 4 27 dep albicans 634:641 arg1 ANP1 661:664 ANP1 661:664 ANP1 661:664 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 4 27 dep albicans 634:641 arg1 OCH1 643:646 OCH1 643:646 OCH1 643:646 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 4 27 dep albicans 634:641 arg1 MNN9 649:652 MNN9 649:652 MNN9 649:652 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 4 27 dep albicans 634:641 arg1 MNN10 667:671 MNN10 667:671 MNN10 667:671 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 2 28 gly glycoproteins 363:375 arg1 glycoproteins 363:375 these glycoproteins 357:375 these glycoproteins 357:375 The asparagine (N)-linked mannose outer chain of these glycoproteins is produced by Golgi mannosyltransferases (MTases). 35333306 8 29 with glycoproteins 1403:1415 arg1 chains 1450:1455 severely truncated N-glycan chains 1422:1455 severely truncated N-glycan chains 1422:1455 Analyses of secreted glycosylation reporters demonstrated that anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains accumulate glycoproteins with severely truncated N-glycan chains. 35333306 9 30 theme increased 1497:1505 arg1 deposition 1514:1523 increased chitin deposition 1497:1523 increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches 1497:1635 This hypo-mannosylation did not elicit increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches. 35333306 6 31 contain have 1125:1128 arg2 phenotypes 1153:1162 no obvious deleterious phenotypes 1130:1162 no obvious deleterious phenotypes 1130:1162 Unexpectedly, and in stark contrast to S. cerevisiae, loss of Anp1, Mnn10, or Mnn11, which together synthesize most of the backbone, have no obvious deleterious phenotypes. 35333306 6 31 contain have 1125:1128 arg1 loss 1046:1049 loss 1046:1049 loss 1046:1049 Unexpectedly, and in stark contrast to S. cerevisiae, loss of Anp1, Mnn10, or Mnn11, which together synthesize most of the backbone, have no obvious deleterious phenotypes. 35333306 0 32 theme N-linked 25:32 arg1 glycan 46:51 The Mnn10/Anp1-dependent N-linked outer chain glycan 0:51 The Mnn10/Anp1-dependent N-linked outer chain glycan 0:51 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 0 32 theme N-linked 25:32 arg1 dispensable 56:66 dispensable 56:66 dispensable 56:66 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 1 33 theme Candida 110:116 arg1 albicans 118:125 Candida albicans 110:125 Candida albicans cell wall glycoproteins 110:149 Candida albicans cell wall glycoproteins, and in particular their mannose-rich glycans, are important for maintaining cellular integrity as well as host recognition, adhesion, and immunomodulation. 35333306 7 34 theme cell 1198:1201 arg1 morphology 1203:1212 cell morphology 1198:1212 cell morphology 1198:1212 These mutants were unaffected in cell morphology, growth, drug sensitivities, hyphal formation, and macrophage recognition. 35333306 3 35 from mannoses 561:568 arg1 linkages 579:586 other linkages 573:586 other linkages 573:586 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 0 36 theme chain 40:44 arg1 glycan 46:51 The Mnn10/Anp1-dependent N-linked outer chain glycan 0:51 The Mnn10/Anp1-dependent N-linked outer chain glycan 0:51 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 0 36 theme chain 40:44 arg1 dispensable 56:66 dispensable 56:66 dispensable 56:66 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 2 37 theme mannose 334:340 arg1 chain 348:352 The asparagine (N)-linked mannose outer chain 308:352 The asparagine (N)-linked mannose outer chain of these glycoproteins 308:375 The asparagine (N)-linked mannose outer chain of these glycoproteins is produced by Golgi mannosyltransferases (MTases). 35333306 9 38 theme key 1579:1581 arg1 response 1596:1603 a key compensatory response 1577:1603 a key compensatory response to cell wall integrity 1577:1626 This hypo-mannosylation did not elicit increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches. 35333306 8 39 theme glycosylation 1310:1322 arg1 reporters 1324:1332 secreted glycosylation reporters 1301:1332 secreted glycosylation reporters 1301:1332 Analyses of secreted glycosylation reporters demonstrated that anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains accumulate glycoproteins with severely truncated N-glycan chains. 35333306 1 40 theme cellular 228:235 arg1 integrity 237:245 cellular integrity 228:245 cellular integrity as well as host recognition, adhesion, and immunomodulation 228:305 Candida albicans cell wall glycoproteins, and in particular their mannose-rich glycans, are important for maintaining cellular integrity as well as host recognition, adhesion, and immunomodulation. 35333306 5 41 theme Saccharomyces 908:920 arg1 counterparts 933:944 their Saccharomyces cerevisiae counterparts 902:944 their Saccharomyces cerevisiae counterparts 902:944 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 3 42 theme mannoses 497:504 arg1 backbone 469:476 a linear backbone 460:476 a linear backbone 460:476 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 3 42 theme mannoses 497:504 arg1 scaffold 523:530 a scaffold 521:530 a scaffold for addition of ∼150 or more mannoses in other linkages 521:586 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 9 43 theme other 1552:1556 arg1 yeast 1558:1562 other yeast 1552:1562 other yeast 1552:1562 This hypo-mannosylation did not elicit increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches. 35333306 3 44 theme ∼50 481:483 arg1 mannoses 497:504 ∼50 α1,6-linked mannoses 481:504 ∼50 α1,6-linked mannoses 481:504 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 5 45 theme van1Δ/Δ 830:836 arg1 mutants 838:844 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants 791:844 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants 791:844 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 9 46 theme compensatory 1583:1594 arg1 response 1596:1603 a key compensatory response 1577:1603 a key compensatory response to cell wall integrity 1577:1626 This hypo-mannosylation did not elicit increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches. 35333306 2 47 link -linked 326:332 arg1 chain 348:352 The asparagine (N)-linked mannose outer chain 308:352 The asparagine (N)-linked mannose outer chain of these glycoproteins 308:375 The asparagine (N)-linked mannose outer chain of these glycoproteins is produced by Golgi mannosyltransferases (MTases). 35333306 9 48 theme cell 1532:1535 arg1 wall 1537:1540 the cell wall 1528:1540 the cell wall 1528:1540 This hypo-mannosylation did not elicit increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches. 35333306 6 49 theme Mnn11 1070:1074 arg1 loss 1046:1049 loss 1046:1049 loss 1046:1049 Unexpectedly, and in stark contrast to S. cerevisiae, loss of Anp1, Mnn10, or Mnn11, which together synthesize most of the backbone, have no obvious deleterious phenotypes. 35333306 6 50 theme deleterious 1141:1151 arg1 phenotypes 1153:1162 no obvious deleterious phenotypes 1130:1162 no obvious deleterious phenotypes 1130:1162 Unexpectedly, and in stark contrast to S. cerevisiae, loss of Anp1, Mnn10, or Mnn11, which together synthesize most of the backbone, have no obvious deleterious phenotypes. 35333306 4 51 theme α1,6 756:759 arg1 backbone 781:788 the α1,6 mannose outer chain backbone 752:788 the α1,6 mannose outer chain backbone 752:788 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 5 52 theme Candida 791:797 arg1 albicans 799:806 Candida albicans 791:806 Candida albicans och1Δ/Δ 791:814 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 4 53 theme outer 769:773 arg1 backbone 781:788 the α1,6 mannose outer chain backbone 752:788 the α1,6 mannose outer chain backbone 752:788 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 5 54 theme cell 959:962 arg1 wall 964:967 severe cell wall and growth phenotypes 952:989 wall 964:967 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 10 55 theme alternate 1671:1679 arg1 mechanism 1681:1689 an alternate mechanism 1668:1689 an alternate mechanism to adapt to cell wall weakness when N-linked mannan levels are reduced 1668:1760 Thus, C. albicans has evolved an alternate mechanism to adapt to cell wall weakness when N-linked mannan levels are reduced. 35333306 3 56 link α1,6-linked 485:495 arg1 mannoses 497:504 ∼50 α1,6-linked mannoses 481:504 ∼50 α1,6-linked mannoses 481:504 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 8 57 theme anp1Δ/Δ 1352:1358 arg1 mnn10Δ/Δ 1361:1368 anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains 1352:1390 mnn10Δ/Δ 1361:1368 Analyses of secreted glycosylation reporters demonstrated that anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains accumulate glycoproteins with severely truncated N-glycan chains. 35333306 1 58 gly glycoproteins 137:149 arg1 glycoproteins 137:149 Candida albicans cell wall glycoproteins 110:149 Candida albicans cell wall glycoproteins 110:149 Candida albicans cell wall glycoproteins, and in particular their mannose-rich glycans, are important for maintaining cellular integrity as well as host recognition, adhesion, and immunomodulation. 35333306 10 59 theme wall 1708:1711 arg1 weakness 1713:1720 cell wall weakness 1703:1720 cell wall weakness 1703:1720 Thus, C. albicans has evolved an alternate mechanism to adapt to cell wall weakness when N-linked mannan levels are reduced. 35333306 7 60 theme macrophage 1265:1274 arg1 recognition 1276:1286 macrophage recognition 1265:1286 macrophage recognition 1265:1286 These mutants were unaffected in cell morphology, growth, drug sensitivities, hyphal formation, and macrophage recognition. 35333306 5 61 dep Saccharomyces 908:920 arg1 cerevisiae 922:931 cerevisiae 922:931 cerevisiae 922:931 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 1 62 theme albicans 118:125 arg1 glycoproteins 137:149 Candida albicans cell wall glycoproteins 110:149 Candida albicans cell wall glycoproteins 110:149 Candida albicans cell wall glycoproteins, and in particular their mannose-rich glycans, are important for maintaining cellular integrity as well as host recognition, adhesion, and immunomodulation. 35333306 4 63 theme conserved 702:710 arg1 albicans 634:641 C. albicans 631:641 C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11 631:682 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 4 63 theme conserved 702:710 arg1 MTases 718:723 the conserved Golgi MTases 698:723 the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone 698:788 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 10 64 theme mannan 1736:1741 arg1 levels 1743:1748 N-linked mannan levels 1727:1748 N-linked mannan levels 1727:1748 Thus, C. albicans has evolved an alternate mechanism to adapt to cell wall weakness when N-linked mannan levels are reduced. 35333306 1 65 theme wall 132:135 arg1 glycoproteins 137:149 Candida albicans cell wall glycoproteins 110:149 Candida albicans cell wall glycoproteins 110:149 Candida albicans cell wall glycoproteins, and in particular their mannose-rich glycans, are important for maintaining cellular integrity as well as host recognition, adhesion, and immunomodulation. 35333306 9 66 from deposition 1514:1523 arg1 wall 1537:1540 the cell wall 1528:1540 the cell wall 1528:1540 This hypo-mannosylation did not elicit increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches. 35333306 7 67 theme hyphal 1243:1248 arg1 formation 1250:1258 hyphal formation 1243:1258 hyphal formation 1243:1258 These mutants were unaffected in cell morphology, growth, drug sensitivities, hyphal formation, and macrophage recognition. 35333306 3 68 from addition 536:543 arg1 linkages 579:586 other linkages 573:586 other linkages 573:586 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 0 69 theme Candida 72:78 arg1 albicans 80:87 Candida albicans 72:87 Candida albicans cell wall integrity 72:107 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 5 70 theme och1Δ/Δ 808:814 arg1 mutants 838:844 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants 791:844 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants 791:844 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 4 71 theme albicans 634:641 arg1 characterization 611:626 the characterization 607:626 the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone 607:788 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 0 72 theme cell 89:92 arg1 integrity 99:107 Candida albicans cell wall integrity 72:107 Candida albicans cell wall integrity 72:107 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 5 73 theme mnn9Δ/Δ 817:823 arg1 mutants 838:844 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants 791:844 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants 791:844 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 9 74 theme cell 1608:1611 arg1 integrity 1618:1626 cell wall integrity 1608:1626 cell wall integrity 1608:1626 This hypo-mannosylation did not elicit increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches. 35333306 5 75 theme backbone 874:881 arg1 synthesis 883:891 backbone synthesis 874:891 backbone synthesis 874:891 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 8 76 theme N-glycan 1441:1448 arg1 chains 1450:1455 severely truncated N-glycan chains 1422:1455 severely truncated N-glycan chains 1422:1455 Analyses of secreted glycosylation reporters demonstrated that anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains accumulate glycoproteins with severely truncated N-glycan chains. 35333306 5 77 dep block 846:850 arg1 have 947:950 have 947:950 have severe cell wall and growth phenotypes 947:989 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 10 78 link N-linked 1727:1734 arg1 levels 1743:1748 N-linked mannan levels 1727:1748 N-linked mannan levels 1727:1748 Thus, C. albicans has evolved an alternate mechanism to adapt to cell wall weakness when N-linked mannan levels are reduced. 35333306 9 79 dep breaches 1628:1635 arg1 wall 1537:1540 the cell wall 1528:1540 the cell wall 1528:1540 This hypo-mannosylation did not elicit increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches. 35333306 3 80 from linkages 579:586 arg1 addition 536:543 addition 536:543 addition of ∼150 or more mannoses in other linkages 536:586 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 3 81 theme outer 433:437 arg1 chain 439:443 The outer chain 429:443 The outer chain 429:443 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 0 82 theme Mnn10/Anp1-dependent 4:23 arg1 glycan 46:51 The Mnn10/Anp1-dependent N-linked outer chain glycan 0:51 The Mnn10/Anp1-dependent N-linked outer chain glycan 0:51 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 0 82 theme Mnn10/Anp1-dependent 4:23 arg1 dispensable 56:66 dispensable 56:66 dispensable 56:66 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 2 83 theme glycoproteins 363:375 arg1 chain 348:352 The asparagine (N)-linked mannose outer chain 308:352 The asparagine (N)-linked mannose outer chain of these glycoproteins 308:375 The asparagine (N)-linked mannose outer chain of these glycoproteins is produced by Golgi mannosyltransferases (MTases). 35333306 0 84 theme outer 34:38 arg1 glycan 46:51 The Mnn10/Anp1-dependent N-linked outer chain glycan 0:51 The Mnn10/Anp1-dependent N-linked outer chain glycan 0:51 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 0 84 theme outer 34:38 arg1 dispensable 56:66 dispensable 56:66 dispensable 56:66 The Mnn10/Anp1-dependent N-linked outer chain glycan is dispensable for Candida albicans cell wall integrity. 35333306 9 85 theme chitin 1507:1512 arg1 deposition 1514:1523 increased chitin deposition 1497:1523 increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches 1497:1635 This hypo-mannosylation did not elicit increased chitin deposition in the cell wall, which in other yeast and fungi is a key compensatory response to cell wall integrity breaches. 35333306 2 86 theme Golgi 392:396 arg1 mannosyltransferases 398:417 Golgi mannosyltransferases 392:417 Golgi mannosyltransferases (MTases) 392:426 The asparagine (N)-linked mannose outer chain of these glycoproteins is produced by Golgi mannosyltransferases (MTases). 35333306 2 86 theme Golgi 392:396 arg1 MTases 420:425 MTases 420:425 MTases 420:425 The asparagine (N)-linked mannose outer chain of these glycoproteins is produced by Golgi mannosyltransferases (MTases). 35333306 5 87 theme severe 952:957 arg1 wall 964:967 severe cell wall and growth phenotypes 952:989 wall 964:967 Candida albicans och1Δ/Δ, mnn9Δ/Δ, and van1Δ/Δ mutants block the earliest steps of backbone synthesis and like their Saccharomyces cerevisiae counterparts, have severe cell wall and growth phenotypes. 35333306 2 88 theme -linked 326:332 arg1 chain 348:352 The asparagine (N)-linked mannose outer chain 308:352 The asparagine (N)-linked mannose outer chain of these glycoproteins 308:375 The asparagine (N)-linked mannose outer chain of these glycoproteins is produced by Golgi mannosyltransferases (MTases). 35333306 4 89 theme Golgi 712:716 arg1 albicans 634:641 C. albicans 631:641 C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11 631:682 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 4 89 theme Golgi 712:716 arg1 MTases 718:723 the conserved Golgi MTases 698:723 the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone 698:788 Here, we describe the characterization of C. albicans OCH1, MNN9, VAN1, ANP1, MNN10, and MNN11, which encode the conserved Golgi MTases that sequentially catalyze the α1,6 mannose outer chain backbone. 35333306 10 90 theme cell 1703:1706 arg1 weakness 1713:1720 cell wall weakness 1703:1720 cell wall weakness 1703:1720 Thus, C. albicans has evolved an alternate mechanism to adapt to cell wall weakness when N-linked mannan levels are reduced. 35333306 8 91 theme secreted 1301:1308 arg1 reporters 1324:1332 secreted glycosylation reporters 1301:1332 secreted glycosylation reporters 1301:1332 Analyses of secreted glycosylation reporters demonstrated that anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains accumulate glycoproteins with severely truncated N-glycan chains. 35333306 3 92 theme linear 462:467 arg1 backbone 469:476 a linear backbone 460:476 a linear backbone 460:476 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 3 92 theme linear 462:467 arg1 scaffold 523:530 a scaffold 521:530 a scaffold for addition of ∼150 or more mannoses in other linkages 521:586 The outer chain is composed of a linear backbone of ∼50 α1,6-linked mannoses, which acts as a scaffold for addition of ∼150 or more mannoses in other linkages. 35333306 8 93 theme reporters 1324:1332 arg1 Analyses 1289:1296 Analyses 1289:1296 Analyses of secreted glycosylation reporters 1289:1332 Analyses of secreted glycosylation reporters demonstrated that anp1Δ/Δ, mnn10Δ/Δ, and mnn11Δ/Δ strains accumulate glycoproteins with severely truncated N-glycan chains. 35267310 0 0 theme Soluble 77:83 arg1 Polysaccharide 85:98 a Hot Water Soluble Polysaccharide 65:98 a Hot Water Soluble Polysaccharide from Hulless Barley Grass 65:124 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 8 1 from grass 1335:1339 arg1 foods 1355:1359 functional foods 1344:1359 functional foods to aid in preventing cancer 1344:1387 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 6 2 contain possessed 940:948 arg1 HBGP 935:938 HBGP 935:938 HBGP 935:938 Based on infrared spectrum analysis, HBGP possessed pyranose and galactose residues. 35267310 6 2 contain possessed 940:948 arg2 residues 973:980 pyranose and galactose residues 950:980 residues 973:980 Based on infrared spectrum analysis, HBGP possessed pyranose and galactose residues. 35267310 2 3 theme chemical 346:353 arg1 characterization 355:370 its chemical characterization 342:370 its chemical characterization 342:370 Here, a hot water soluble polysaccharide was extracted from hulless barley grass, and its chemical characterization and in vitro anti-cancer activities were investigated. 35267310 8 4 theme barley 1328:1333 arg1 grass 1335:1339 hulless barley grass 1320:1339 hulless barley grass in functional foods to aid in preventing cancer 1320:1387 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 0 5 from Characterization 9:24 arg1 Grass 120:124 Hulless Barley Grass 105:124 Hulless Barley Grass 105:124 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 1 6 theme many 159:162 arg1 benefits 171:178 many health benefits 159:178 many health benefits attributed to its bioactive functional components, such as polysaccharides 159:253 Hulless barley grass may confer many health benefits attributed to its bioactive functional components, such as polysaccharides. 35267310 5 7 theme % 854:854 arg1 arabinose 856:864 25.6% arabinose 850:864 25.6% arabinose 850:864 The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. 35267310 3 8 theme high 644:647 arg1 column 665:670 an S-400 high resolution (HR) column 635:670 an S-400 high resolution (HR) column 635:670 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 4 9 theme molecular 713:721 arg1 weight 723:728 number-average molecular weight 698:728 number-average molecular weight 698:728 The molecular weight and number-average molecular weight of HBGP were 3.3 × 104 and 2.9 × 104 Da, respectively. 35267310 5 10 theme 5.5 867:869 arg1 % 870:870 % 870:870 % 870:870 The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. 35267310 0 11 theme Polysaccharide 85:98 arg1 Activities 51:60 In Vitro Anti-Cancer Activities 30:60 In Vitro Anti-Cancer Activities 30:60 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 0 11 theme Polysaccharide 85:98 arg1 Characterization 9:24 Chemical Characterization 0:24 Chemical Characterization 0:24 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 3 12 theme S-400 638:642 arg1 column 665:670 an S-400 high resolution (HR) column 635:670 an S-400 high resolution (HR) column 635:670 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 4 13 theme number-average 698:711 arg1 weight 723:728 number-average molecular weight 698:728 number-average molecular weight 698:728 The molecular weight and number-average molecular weight of HBGP were 3.3 × 104 and 2.9 × 104 Da, respectively. 35267310 2 14 theme soluble 274:280 arg1 polysaccharide 282:295 a hot water soluble polysaccharide 262:295 a hot water soluble polysaccharide 262:295 Here, a hot water soluble polysaccharide was extracted from hulless barley grass, and its chemical characterization and in vitro anti-cancer activities were investigated. 35267310 8 15 from development 1289:1299 arg1 foods 1355:1359 functional foods 1344:1359 functional foods to aid in preventing cancer 1344:1387 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 2 16 theme barley 324:329 arg1 grass 331:335 hulless barley grass 316:335 hulless barley grass 316:335 Here, a hot water soluble polysaccharide was extracted from hulless barley grass, and its chemical characterization and in vitro anti-cancer activities were investigated. 35267310 0 17 theme Barley 113:118 arg1 Grass 120:124 Hulless Barley Grass 105:124 Hulless Barley Grass 105:124 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 0 18 from Activities 51:60 arg1 Grass 120:124 Hulless Barley Grass 105:124 Hulless Barley Grass 105:124 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 4 19 theme molecular 677:685 arg1 weight 687:692 The molecular weight 673:692 The molecular weight 673:692 The molecular weight and number-average molecular weight of HBGP were 3.3 × 104 and 2.9 × 104 Da, respectively. 35267310 4 19 theme molecular 677:685 arg1 Da 767:768 3.3 × 104 and 2.9 × 104 Da 743:768 3.3 × 104 and 2.9 × 104 Da 743:768 The molecular weight and number-average molecular weight of HBGP were 3.3 × 104 and 2.9 × 104 Da, respectively. 35267310 2 20 theme water 268:272 arg1 polysaccharide 282:295 a hot water soluble polysaccharide 262:295 a hot water soluble polysaccharide 262:295 Here, a hot water soluble polysaccharide was extracted from hulless barley grass, and its chemical characterization and in vitro anti-cancer activities were investigated. 35267310 4 21 theme HBGP 733:736 arg1 weight 687:692 The molecular weight 673:692 The molecular weight 673:692 The molecular weight and number-average molecular weight of HBGP were 3.3 × 104 and 2.9 × 104 Da, respectively. 35267310 4 21 theme HBGP 733:736 arg1 weight 723:728 number-average molecular weight 698:728 number-average molecular weight 698:728 The molecular weight and number-average molecular weight of HBGP were 3.3 × 104 and 2.9 × 104 Da, respectively. 35267310 4 21 theme HBGP 733:736 arg1 Da 767:768 3.3 × 104 and 2.9 × 104 Da 743:768 3.3 × 104 and 2.9 × 104 Da 743:768 The molecular weight and number-average molecular weight of HBGP were 3.3 × 104 and 2.9 × 104 Da, respectively. 35267310 1 22 theme health 164:169 arg1 benefits 171:178 many health benefits 159:178 many health benefits attributed to its bioactive functional components, such as polysaccharides 159:253 Hulless barley grass may confer many health benefits attributed to its bioactive functional components, such as polysaccharides. 35267310 0 23 theme Hulless 105:111 arg1 Grass 120:124 Hulless Barley Grass 105:124 Hulless Barley Grass 105:124 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 3 24 theme HR 661:662 arg1 column 665:670 an S-400 high resolution (HR) column 635:670 an S-400 high resolution (HR) column 635:670 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 7 25 theme proliferation 1054:1066 arg1 effects 1079:1085 significant cell proliferation inhibitory effects 1037:1085 significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT 1037:1142 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 26 theme half-inhibitory 1197:1211 arg1 value 1232:1236 the half-inhibitory concentration IC50 value 1193:1236 the half-inhibitory concentration IC50 value 1193:1236 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 2 27 theme hot 264:266 arg1 polysaccharide 282:295 a hot water soluble polysaccharide 262:295 a hot water soluble polysaccharide 262:295 Here, a hot water soluble polysaccharide was extracted from hulless barley grass, and its chemical characterization and in vitro anti-cancer activities were investigated. 35267310 2 28 theme anti-cancer 385:395 arg1 activities 397:406 in vitro anti-cancer activities 376:406 in vitro anti-cancer activities 376:406 Here, a hot water soluble polysaccharide was extracted from hulless barley grass, and its chemical characterization and in vitro anti-cancer activities were investigated. 35267310 5 29 theme % 888:888 arg1 xylose 890:895 5.3% xylose 885:895 5.3% xylose 885:895 The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. 35267310 5 30 theme 35.1 833:836 arg1 % 837:837 % 837:837 % 837:837 The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. 35267310 2 31 theme hulless 316:322 arg1 grass 331:335 hulless barley grass 316:335 hulless barley grass 316:335 Here, a hot water soluble polysaccharide was extracted from hulless barley grass, and its chemical characterization and in vitro anti-cancer activities were investigated. 35267310 7 32 theme cancer 1095:1100 arg1 4T1 1127:1129 4T1 1127:1129 4T1 1127:1129 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 32 theme cancer 1095:1100 arg1 lines 1107:1111 cancer cell lines HT29, Caco-2, 4T1, and CT26.WT 1095:1142 cancer cell lines HT29, Caco-2, 4T1, and CT26.WT 1095:1142 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 32 theme cancer 1095:1100 arg1 Caco-2 1119:1124 Caco-2 1119:1124 Caco-2 1119:1124 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 32 theme cancer 1095:1100 arg1 CT26.WT 1136:1142 CT26.WT 1136:1142 CT26.WT 1136:1142 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 32 theme cancer 1095:1100 arg1 HT29 1113:1116 HT29 1113:1116 HT29 1113:1116 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 5 33 theme monosaccharide 789:802 arg1 composition 804:814 The monosaccharide composition 785:814 The monosaccharide composition of HBGP 785:822 The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. 35267310 0 34 theme Chemical 0:7 arg1 Characterization 9:24 Chemical Characterization 0:24 Chemical Characterization 0:24 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 8 35 from foods 1355:1359 arg1 utilization 1305:1315 utilization 1305:1315 utilization 1305:1315 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 8 35 from foods 1355:1359 arg1 development 1289:1299 development 1289:1299 development 1289:1299 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 2 36 theme in 376:377 arg1 activities 397:406 in vitro anti-cancer activities 376:406 in vitro anti-cancer activities 376:406 Here, a hot water soluble polysaccharide was extracted from hulless barley grass, and its chemical characterization and in vitro anti-cancer activities were investigated. 35267310 0 37 theme In 30:31 arg1 Activities 51:60 In Vitro Anti-Cancer Activities 30:60 In Vitro Anti-Cancer Activities 30:60 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 4 38 theme × 747:747 arg1 weight 687:692 The molecular weight 673:692 The molecular weight 673:692 The molecular weight and number-average molecular weight of HBGP were 3.3 × 104 and 2.9 × 104 Da, respectively. 35267310 4 38 theme × 747:747 arg1 Da 767:768 3.3 × 104 and 2.9 × 104 Da 743:768 3.3 × 104 and 2.9 × 104 Da 743:768 The molecular weight and number-average molecular weight of HBGP were 3.3 × 104 and 2.9 × 104 Da, respectively. 35267310 7 39 theme water-soluble 1001:1013 arg1 polysaccharide 1015:1028 this water-soluble polysaccharide 996:1028 this water-soluble polysaccharide 996:1028 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 5 40 theme 25.6 850:853 arg1 % 854:854 % 854:854 % 854:854 The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. 35267310 6 41 theme galactose 963:971 arg1 residues 973:980 pyranose and galactose residues 950:980 residues 973:980 Based on infrared spectrum analysis, HBGP possessed pyranose and galactose residues. 35267310 5 42 theme % 870:870 arg1 glucose 872:878 5.5% glucose 867:878 5.5% glucose 867:878 The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. 35267310 8 43 theme hulless 1320:1326 arg1 grass 1335:1339 hulless barley grass 1320:1339 hulless barley grass in functional foods to aid in preventing cancer 1320:1387 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 8 44 theme grass 1335:1339 arg1 utilization 1305:1315 utilization 1305:1315 utilization 1305:1315 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 8 44 theme grass 1335:1339 arg1 development 1289:1299 development 1289:1299 development 1289:1299 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 3 45 theme polydispersity 529:542 arg1 PDI 551:553 PDI 551:553 PDI 551:553 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 3 45 theme polydispersity 529:542 arg1 index 544:548 a polydispersity index 527:548 a polydispersity index (PDI) of 1.11 527:562 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 8 46 from utilization 1305:1315 arg1 foods 1355:1359 functional foods 1344:1359 functional foods to aid in preventing cancer 1344:1387 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 1 47 theme bioactive 198:206 arg1 polysaccharides 239:253 polysaccharides 239:253 polysaccharides 239:253 Hulless barley grass may confer many health benefits attributed to its bioactive functional components, such as polysaccharides. 35267310 1 47 theme bioactive 198:206 arg1 components 219:228 its bioactive functional components 194:228 its bioactive functional components 194:228 Hulless barley grass may confer many health benefits attributed to its bioactive functional components, such as polysaccharides. 35267310 0 48 theme Anti-Cancer 39:49 arg1 Activities 51:60 In Vitro Anti-Cancer Activities 30:60 In Vitro Anti-Cancer Activities 30:60 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 8 49 dep foods 1355:1359 arg1 aid 1364:1366 aid 1364:1366 to aid in preventing cancer 1361:1387 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 7 50 dep HT29 1187:1190 arg1 = 1238:1238 = 1238:1238 = 1238:1238 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 3 51 theme DE-32 617:621 arg1 column 624:629 a diethylaminoethyl cellulose (DE-32) column 586:629 a diethylaminoethyl cellulose (DE-32) column 586:629 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 6 52 theme pyranose 950:957 arg1 residues 973:980 pyranose and galactose residues 950:980 residues 973:980 Based on infrared spectrum analysis, HBGP possessed pyranose and galactose residues. 35267310 1 53 theme functional 208:217 arg1 polysaccharides 239:253 polysaccharides 239:253 polysaccharides 239:253 Hulless barley grass may confer many health benefits attributed to its bioactive functional components, such as polysaccharides. 35267310 1 53 theme functional 208:217 arg1 components 219:228 its bioactive functional components 194:228 its bioactive functional components 194:228 Hulless barley grass may confer many health benefits attributed to its bioactive functional components, such as polysaccharides. 35267310 3 54 theme hulless 440:446 arg1 polysaccharide 461:474 hulless barley grass polysaccharide 440:474 hulless barley grass polysaccharide (HBGP) 440:481 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 3 54 theme hulless 440:446 arg1 HBGP 477:480 HBGP 477:480 HBGP 477:480 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 7 55 theme inhibitory 1068:1077 arg1 effects 1079:1085 significant cell proliferation inhibitory effects 1037:1085 significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT 1037:1142 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 3 56 theme diethylaminoethyl 588:604 arg1 column 624:629 a diethylaminoethyl cellulose (DE-32) column 586:629 a diethylaminoethyl cellulose (DE-32) column 586:629 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 3 57 theme 1.11 559:562 arg1 PDI 551:553 PDI 551:553 PDI 551:553 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 3 57 theme 1.11 559:562 arg1 index 544:548 a polydispersity index 527:548 a polydispersity index (PDI) of 1.11 527:562 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 3 58 theme polysaccharide 461:474 arg1 yield 431:435 The yield 427:435 The yield of hulless barley grass polysaccharide (HBGP) 427:481 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 3 58 theme polysaccharide 461:474 arg1 % 490:490 2.3% 487:490 2.3% 487:490 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 7 59 theme significant 1037:1047 arg1 effects 1079:1085 significant cell proliferation inhibitory effects 1037:1085 significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT 1037:1142 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 60 dep lines 1107:1111 arg1 lines 1107:1111 cancer cell lines HT29, Caco-2, 4T1, and CT26.WT 1095:1142 cancer cell lines HT29, Caco-2, 4T1, and CT26.WT 1095:1142 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 60 dep lines 1107:1111 arg1 4T1 1127:1129 4T1 1127:1129 4T1 1127:1129 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 60 dep lines 1107:1111 arg1 CT26.WT 1136:1142 CT26.WT 1136:1142 CT26.WT 1136:1142 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 60 dep lines 1107:1111 arg1 Caco-2 1119:1124 Caco-2 1119:1124 Caco-2 1119:1124 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 60 dep lines 1107:1111 arg1 HT29 1113:1116 HT29 1113:1116 HT29 1113:1116 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 3 61 theme cellulose 606:614 arg1 column 624:629 a diethylaminoethyl cellulose (DE-32) column 586:629 a diethylaminoethyl cellulose (DE-32) column 586:629 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 5 62 theme % 837:837 arg1 galactose 839:847 35.1% galactose 833:847 35.1% galactose 833:847 The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. 35267310 7 63 theme cell 1049:1052 arg1 effects 1079:1085 significant cell proliferation inhibitory effects 1037:1085 significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT 1037:1142 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 64 theme IC50 1227:1230 arg1 value 1232:1236 the half-inhibitory concentration IC50 value 1193:1236 the half-inhibitory concentration IC50 value 1193:1236 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 8 65 theme functional 1344:1353 arg1 foods 1355:1359 functional foods 1344:1359 functional foods to aid in preventing cancer 1344:1387 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 7 66 theme dose-dependent 1149:1162 arg1 manner 1164:1169 a dose-dependent manner 1147:1169 a dose-dependent manner 1147:1169 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 5 67 theme 5.3 885:887 arg1 % 888:888 % 888:888 % 888:888 The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. 35267310 0 68 dep In 30:31 arg1 Vitro 33:37 Vitro 33:37 Vitro 33:37 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 1 69 theme Hulless 127:133 arg1 grass 142:146 Hulless barley grass 127:146 Hulless barley grass 127:146 Hulless barley grass may confer many health benefits attributed to its bioactive functional components, such as polysaccharides. 35267310 6 70 theme spectrum 916:923 arg1 analysis 925:932 infrared spectrum analysis 907:932 infrared spectrum analysis 907:932 Based on infrared spectrum analysis, HBGP possessed pyranose and galactose residues. 35267310 2 71 dep in 376:377 arg1 vitro 379:383 vitro 379:383 vitro 379:383 Here, a hot water soluble polysaccharide was extracted from hulless barley grass, and its chemical characterization and in vitro anti-cancer activities were investigated. 35267310 1 72 theme barley 135:140 arg1 grass 142:146 Hulless barley grass 127:146 Hulless barley grass 127:146 Hulless barley grass may confer many health benefits attributed to its bioactive functional components, such as polysaccharides. 35267310 7 73 theme concentration 1213:1225 arg1 value 1232:1236 the half-inhibitory concentration IC50 value 1193:1236 the half-inhibitory concentration IC50 value 1193:1236 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 6 74 theme infrared 907:914 arg1 analysis 925:932 infrared spectrum analysis 907:932 infrared spectrum analysis 907:932 Based on infrared spectrum analysis, HBGP possessed pyranose and galactose residues. 35267310 0 75 theme Hot 67:69 arg1 Polysaccharide 85:98 a Hot Water Soluble Polysaccharide 65:98 a Hot Water Soluble Polysaccharide from Hulless Barley Grass 65:124 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 3 76 theme grass 455:459 arg1 polysaccharide 461:474 hulless barley grass polysaccharide 440:474 hulless barley grass polysaccharide (HBGP) 440:481 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 3 76 theme grass 455:459 arg1 HBGP 477:480 HBGP 477:480 HBGP 477:480 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 8 77 dep development 1289:1299 arg1 the 1285:1287 the 1285:1287 the 1285:1287 The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer. 35267310 3 78 theme barley 448:453 arg1 polysaccharide 461:474 hulless barley grass polysaccharide 440:474 hulless barley grass polysaccharide (HBGP) 440:481 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 3 78 theme barley 448:453 arg1 HBGP 477:480 HBGP 477:480 HBGP 477:480 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 3 79 theme resolution 649:658 arg1 column 665:670 an S-400 high resolution (HR) column 635:670 an S-400 high resolution (HR) column 635:670 The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. 35267310 5 80 theme HBGP 819:822 arg1 composition 804:814 The monosaccharide composition 785:814 The monosaccharide composition of HBGP 785:822 The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. 35267310 7 81 theme cell 1102:1105 arg1 4T1 1127:1129 4T1 1127:1129 4T1 1127:1129 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 81 theme cell 1102:1105 arg1 lines 1107:1111 cancer cell lines HT29, Caco-2, 4T1, and CT26.WT 1095:1142 cancer cell lines HT29, Caco-2, 4T1, and CT26.WT 1095:1142 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 81 theme cell 1102:1105 arg1 Caco-2 1119:1124 Caco-2 1119:1124 Caco-2 1119:1124 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 81 theme cell 1102:1105 arg1 CT26.WT 1136:1142 CT26.WT 1136:1142 CT26.WT 1136:1142 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 7 81 theme cell 1102:1105 arg1 HT29 1113:1116 HT29 1113:1116 HT29 1113:1116 In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). 35267310 0 82 from Grass 120:124 arg1 Activities 51:60 In Vitro Anti-Cancer Activities 30:60 In Vitro Anti-Cancer Activities 30:60 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 0 82 from Grass 120:124 arg1 Characterization 9:24 Chemical Characterization 0:24 Chemical Characterization 0:24 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 35267310 0 82 from Grass 120:124 arg1 Polysaccharide 85:98 a Hot Water Soluble Polysaccharide 65:98 a Hot Water Soluble Polysaccharide from Hulless Barley Grass 65:124 Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass. 36168850 3 0 theme N-glycans 352:360 arg1 nature 342:347 the hydrophilic nature 326:347 the hydrophilic nature of N-glycans 326:360 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 1 1 theme disease 174:180 arg1 progression 182:192 the disease progression 170:192 the disease progression 170:192 Human serum N-linked glycans expression levels change during the disease progression. 36168850 0 2 theme cellulose/polymer 79:95 arg1 nanohybrid 97:106 the newly developed asparagine immobilized cellulose/polymer nanohybrid 36:106 the newly developed asparagine immobilized cellulose/polymer nanohybrid 36:106 Human serum N-glycome profiling via the newly developed asparagine immobilized cellulose/polymer nanohybrid. 36168850 6 3 theme nanohybrid/asparagine 1071:1091 arg1 capability 1057:1066 The enrichment capability 1042:1066 The enrichment capability of nanohybrid/asparagine 1042:1091 The enrichment capability of nanohybrid/asparagine is assessed by the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively. 36168850 7 4 dep 100 1338:1340 arg1 to 1335:1336 to 1335:1336 to 1335:1336 The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. 36168850 7 5 with sensitivity 1318:1328 arg1 albumin 1306:1312 spiked bovine serum albumin 1286:1312 spiked bovine serum albumin 1286:1312 The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. 36168850 8 6 theme Human 1352:1356 arg1 profiling 1364:1372 Human serum profiling 1352:1372 Human serum profiling for N-glycans 1352:1386 Human serum profiling for N-glycans identifies 52 glycan structures. 36168850 7 7 theme spiked 1286:1291 arg1 albumin 1306:1312 spiked bovine serum albumin 1286:1312 spiked bovine serum albumin 1286:1312 The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. 36168850 7 8 theme serum 1300:1304 arg1 albumin 1306:1312 spiked bovine serum albumin 1286:1312 spiked bovine serum albumin 1286:1312 The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. 36168850 4 9 theme electron 701:708 arg1 microscopy 710:719 scanning electron microscopy 692:719 scanning electron microscopy 692:719 The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. 36168850 5 10 theme × 866:866 arg1 m2 872:873 2.09 × 102 m2 /g 861:876 2.09 × 102 m2 /g 861:876 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 5 10 theme × 866:866 arg1 area 823:826 The large surface area 805:826 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) 805:877 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 7 11 with selectivity 1259:1269 arg1 albumin 1306:1312 spiked bovine serum albumin 1286:1312 spiked bovine serum albumin 1286:1312 The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. 36168850 9 12 theme serum 1529:1533 arg1 salts 1501:1505 salts 1501:1505 salts 1501:1505 This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth. 36168850 9 12 theme serum 1529:1533 arg1 peptides 1535:1542 endogenous serum peptides 1518:1542 endogenous serum peptides 1518:1542 This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth. 36168850 4 13 theme scanning 692:699 arg1 microscopy 710:719 scanning electron microscopy 692:719 scanning electron microscopy 692:719 The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. 36168850 3 14 theme 1,2-Epoxy-5-hexene 382:399 arg1 nanohybrid 402:411 cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid 363:411 cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid 363:411 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 6 15 theme enrichment 1046:1055 arg1 capability 1057:1066 The enrichment capability 1042:1066 The enrichment capability of nanohybrid/asparagine 1042:1091 The enrichment capability of nanohybrid/asparagine is assessed by the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively. 36168850 5 16 theme interaction 969:979 arg1 chromatography 988:1001 better hydrophilic interaction liquid chromatography 950:1001 better hydrophilic interaction liquid chromatography enrichment under optimized conditions 950:1039 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 4 17 theme X-ray 740:744 arg1 spectroscopy 746:757 energy dispersive X-ray spectroscopy 722:757 energy dispersive X-ray spectroscopy 722:757 The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. 36168850 3 18 theme phase 493:497 arg1 extraction 499:508 solid phase extraction 487:508 solid phase extraction 487:508 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 6 19 theme immunoglobulin 1157:1170 arg1 G 1172:1172 immunoglobulin G 1157:1172 immunoglobulin G 1157:1172 The enrichment capability of nanohybrid/asparagine is assessed by the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively. 36168850 9 20 theme salts 1501:1505 arg1 presence 1489:1496 the presence 1485:1496 the presence of salts, proteins, endogenous serum peptides 1485:1542 This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth. 36168850 5 21 theme immobilization 922:935 arg1 density 900:906 the high density 891:906 the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions 891:1039 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 9 22 theme enrichment 1430:1439 arg1 strategy 1441:1448 This new enrichment strategy 1421:1448 This new enrichment strategy 1421:1448 This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth. 36168850 2 23 theme spectrometry 291:302 arg1 analysis 304:311 mass spectrometry analysis 286:311 mass spectrometry analysis 286:311 The low abundance, structural diversity, and coexisting matrices hinder their detection in mass spectrometry analysis. 36168850 4 24 theme Fourier-transform 764:780 arg1 spectroscopy 791:802 Fourier-transform infrared spectroscopy 764:802 Fourier-transform infrared spectroscopy 764:802 The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. 36168850 0 25 theme serum 6:10 arg1 N-glycome 12:20 Human serum N-glycome 0:20 Human serum N-glycome 0:20 Human serum N-glycome profiling via the newly developed asparagine immobilized cellulose/polymer nanohybrid. 36168850 9 26 theme endogenous 1518:1527 arg1 salts 1501:1505 salts 1501:1505 salts 1501:1505 This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth. 36168850 9 26 theme endogenous 1518:1527 arg1 peptides 1535:1542 endogenous serum peptides 1518:1542 endogenous serum peptides 1518:1542 This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth. 36168850 7 27 theme 1:1200 1274:1279 arg1 selectivity 1259:1269 selectivity 1259:1269 selectivity of 1:1200 with spiked bovine serum albumin 1259:1312 The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. 36168850 7 27 theme 1:1200 1274:1279 arg1 sensitivity 1318:1328 sensitivity 1318:1328 sensitivity down to 100 attomole 1318:1349 The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. 36168850 0 28 theme immobilized 67:77 arg1 nanohybrid 97:106 the newly developed asparagine immobilized cellulose/polymer nanohybrid 36:106 the newly developed asparagine immobilized cellulose/polymer nanohybrid 36:106 Human serum N-glycome profiling via the newly developed asparagine immobilized cellulose/polymer nanohybrid. 36168850 5 29 theme optimized 1020:1028 arg1 conditions 1030:1039 optimized conditions 1020:1039 optimized conditions 1020:1039 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 0 30 theme Human 0:4 arg1 N-glycome 12:20 Human serum N-glycome 0:20 Human serum N-glycome 0:20 Human serum N-glycome profiling via the newly developed asparagine immobilized cellulose/polymer nanohybrid. 36168850 4 31 theme surface 653:659 arg1 properties 661:670 surface properties 653:670 surface properties 653:670 The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. 36168850 7 32 dep attomole 1342:1349 arg1 100 1338:1340 100 1338:1340 100 1338:1340 The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. 36168850 1 33 theme Human 109:113 arg1 levels 149:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels change during the disease progression. 36168850 3 34 theme solid 487:491 arg1 extraction 499:508 solid phase extraction 487:508 solid phase extraction 487:508 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 8 35 theme serum 1358:1362 arg1 profiling 1364:1372 Human serum profiling 1352:1372 Human serum profiling for N-glycans 1352:1386 Human serum profiling for N-glycans identifies 52 glycan structures. 36168850 1 36 theme serum 115:119 arg1 levels 149:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels change during the disease progression. 36168850 3 37 theme interaction 528:538 arg1 chromatography 547:560 hydrophilic interaction liquid chromatography sorbent 516:568 hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine) 516:610 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 3 37 theme interaction 528:538 arg1 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 5 38 theme better 950:955 arg1 chromatography 988:1001 better hydrophilic interaction liquid chromatography 950:1001 better hydrophilic interaction liquid chromatography enrichment under optimized conditions 950:1039 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 5 39 theme cellulose/polymer 831:847 arg1 nanohybrid 849:858 cellulose/polymer nanohybrid 831:858 cellulose/polymer nanohybrid 831:858 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 9 40 theme new 1426:1428 arg1 strategy 1441:1448 This new enrichment strategy 1421:1448 This new enrichment strategy 1421:1448 This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth. 36168850 1 41 theme N-linked 121:128 arg1 levels 149:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels change during the disease progression. 36168850 3 42 theme liquid 540:545 arg1 chromatography 547:560 hydrophilic interaction liquid chromatography sorbent 516:568 hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine) 516:610 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 3 42 theme liquid 540:545 arg1 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 5 43 theme high 895:898 arg1 density 900:906 the high density 891:906 the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions 891:1039 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 5 44 theme nanohybrid 849:858 arg1 area 823:826 The large surface area 805:826 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) 805:877 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 5 44 theme nanohybrid 849:858 arg1 m2 872:873 2.09 × 102 m2 /g 861:876 2.09 × 102 m2 /g 861:876 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 2 45 theme low 199:201 arg1 abundance 203:211 The low abundance 195:211 The low abundance 195:211 The low abundance, structural diversity, and coexisting matrices hinder their detection in mass spectrometry analysis. 36168850 5 46 theme liquid 981:986 arg1 chromatography 988:1001 better hydrophilic interaction liquid chromatography 950:1001 better hydrophilic interaction liquid chromatography enrichment under optimized conditions 950:1039 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 4 47 theme infrared 782:789 arg1 spectroscopy 791:802 Fourier-transform infrared spectroscopy 764:802 Fourier-transform infrared spectroscopy 764:802 The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. 36168850 4 48 theme elemental 629:637 arg1 analysis 639:646 elemental analysis 629:646 elemental analysis 629:646 The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. 36168850 8 49 theme glycan 1402:1407 arg1 structures 1409:1418 52 glycan structures 1399:1418 52 glycan structures 1399:1418 Human serum profiling for N-glycans identifies 52 glycan structures. 36168850 3 50 theme hydrophilic 516:526 arg1 chromatography 547:560 hydrophilic interaction liquid chromatography sorbent 516:568 hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine) 516:610 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 3 50 theme hydrophilic 516:526 arg1 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 0 51 theme developed 46:54 arg1 nanohybrid 97:106 the newly developed asparagine immobilized cellulose/polymer nanohybrid 36:106 the newly developed asparagine immobilized cellulose/polymer nanohybrid 36:106 Human serum N-glycome profiling via the newly developed asparagine immobilized cellulose/polymer nanohybrid. 36168850 6 52 theme N-Linked 1112:1119 arg1 glycans 1121:1127 the N-Linked glycans 1108:1127 the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively 1108:1224 The enrichment capability of nanohybrid/asparagine is assessed by the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively. 36168850 0 53 theme asparagine 56:65 arg1 nanohybrid 97:106 the newly developed asparagine immobilized cellulose/polymer nanohybrid 36:106 the newly developed asparagine immobilized cellulose/polymer nanohybrid 36:106 Human serum N-glycome profiling via the newly developed asparagine immobilized cellulose/polymer nanohybrid. 36168850 2 54 theme coexisting 240:249 arg1 matrices 251:258 coexisting matrices 240:258 coexisting matrices 240:258 The low abundance, structural diversity, and coexisting matrices hinder their detection in mass spectrometry analysis. 36168850 1 55 theme glycans 130:136 arg1 levels 149:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels change during the disease progression. 36168850 5 56 theme asparagine 911:920 arg1 immobilization 922:935 asparagine immobilization 911:935 asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions 911:1039 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 5 57 theme large 809:813 arg1 area 823:826 The large surface area 805:826 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) 805:877 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 5 57 theme large 809:813 arg1 m2 872:873 2.09 × 102 m2 /g 861:876 2.09 × 102 m2 /g 861:876 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 9 58 theme serum 1459:1463 arg1 glycans 1474:1480 serum N-linked glycans 1459:1480 serum N-linked glycans 1459:1480 This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth. 36168850 7 59 theme bovine 1293:1298 arg1 albumin 1306:1312 spiked bovine serum albumin 1286:1312 spiked bovine serum albumin 1286:1312 The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. 36168850 1 60 theme expression 138:147 arg1 levels 149:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels change during the disease progression. 36168850 5 61 theme surface 815:821 arg1 area 823:826 The large surface area 805:826 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) 805:877 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 5 61 theme surface 815:821 arg1 m2 872:873 2.09 × 102 m2 /g 861:876 2.09 × 102 m2 /g 861:876 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 9 62 theme N-linked 1465:1472 arg1 glycans 1474:1480 serum N-linked glycans 1459:1480 serum N-linked glycans 1459:1480 This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth. 36168850 2 63 theme mass 286:289 arg1 analysis 304:311 mass spectrometry analysis 286:311 mass spectrometry analysis 286:311 The low abundance, structural diversity, and coexisting matrices hinder their detection in mass spectrometry analysis. 36168850 3 64 theme hydrophilic 330:340 arg1 nature 342:347 the hydrophilic nature 326:347 the hydrophilic nature of N-glycans 326:360 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 2 65 theme structural 214:223 arg1 diversity 225:233 structural diversity 214:233 structural diversity 214:233 The low abundance, structural diversity, and coexisting matrices hinder their detection in mass spectrometry analysis. 36168850 5 66 dep chromatography 988:1001 arg1 enrichment 1003:1012 enrichment 1003:1012 enrichment 1003:1012 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 3 67 theme sorbent 562:568 arg1 chromatography 547:560 hydrophilic interaction liquid chromatography sorbent 516:568 hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine) 516:610 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 3 67 theme sorbent 562:568 arg1 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 cellulose/1,2-Epoxy-5-hexene/asparagine 571:609 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 3 68 theme cellulose/polymer 363:379 arg1 nanohybrid 402:411 cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid 363:411 cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid 363:411 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 6 69 attach released 1129:1136 arg1 ovalbumin 1143:1151 ovalbumin 1143:1151 ovalbumin 1143:1151 The enrichment capability of nanohybrid/asparagine is assessed by the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively. 36168850 6 69 attach released 1129:1136 arg2 glycans 1121:1127 the N-Linked glycans 1108:1127 the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively 1108:1224 The enrichment capability of nanohybrid/asparagine is assessed by the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively. 36168850 6 69 attach released 1129:1136 arg1 G 1172:1172 immunoglobulin G 1157:1172 immunoglobulin G 1157:1172 The enrichment capability of nanohybrid/asparagine is assessed by the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively. 36168850 5 70 theme hydrophilic 957:967 arg1 chromatography 988:1001 better hydrophilic interaction liquid chromatography 950:1001 better hydrophilic interaction liquid chromatography enrichment under optimized conditions 950:1039 The large surface area of cellulose/polymer nanohybrid (2.09 × 102 m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. 36168850 9 71 link N-linked 1465:1472 arg1 glycans 1474:1480 serum N-linked glycans 1459:1480 serum N-linked glycans 1459:1480 This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth. 36168850 4 72 theme dispersive 729:738 arg1 spectroscopy 746:757 energy dispersive X-ray spectroscopy 722:757 energy dispersive X-ray spectroscopy 722:757 The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. 36168850 1 73 link N-linked 121:128 arg1 levels 149:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels 109:154 Human serum N-linked glycans expression levels change during the disease progression. 36168850 7 74 dep sensitivity 1318:1328 arg1 attomole 1342:1349 attomole 1342:1349 attomole 1342:1349 The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. 36168850 3 75 theme oxirane 432:438 arg1 groups 440:445 oxirane groups 432:445 oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine) 432:610 Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). 36168850 4 76 theme energy 722:727 arg1 spectroscopy 746:757 energy dispersive X-ray spectroscopy 722:757 energy dispersive X-ray spectroscopy 722:757 The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. 37215435 8 0 theme electrical 1367:1376 arg1 stimulation 1378:1388 electrical stimulation 1367:1388 electrical stimulation 1367:1388 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 6 1 theme cell 1069:1072 arg1 proliferation 1074:1086 nerve cell proliferation 1063:1086 nerve cell proliferation 1063:1086 In addition, the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth was demonstrated. 37215435 1 2 theme more 159:162 arg1 patients 173:180 more and more patients 159:180 more and more patients 159:180 Currently, more and more patients suffer from peripheral nerve injury due to trauma, tumor and other causes worldwide. 37215435 4 3 theme polylactic-co-glycolic 614:635 arg1 acid 637:640 polylactic-co-glycolic acid 614:640 polylactic-co-glycolic acid 614:640 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 5 4 theme nerve 992:996 arg1 injury 998:1003 severe peripheral nerve injury 974:1003 severe peripheral nerve injury 974:1003 LBP were confirmed to accelerate long-distance axon regeneration after severe peripheral nerve injury. 37215435 4 5 theme nanofibers 877:886 arg1 layers 863:868 the core and shell layers 844:868 layers 863:868 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 2 6 theme nerve 358:362 arg1 autografts 364:373 nerve autografts 358:373 nerve autografts 358:373 Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. 37215435 1 7 theme other 243:247 arg1 causes 249:254 other causes 243:254 other causes 243:254 Currently, more and more patients suffer from peripheral nerve injury due to trauma, tumor and other causes worldwide. 37215435 0 8 theme barbarum 98:105 arg1 polysaccharides 107:121 Lycium barbarum polysaccharides 91:121 Lycium barbarum polysaccharides 91:121 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 9 9 used used 1627:1630 arg2 fibers 1582:1587 conductive composite fibers 1561:1587 conductive composite fibers with optimized fiber alignment 1561:1618 Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery. 37215435 8 10 with combination 1318:1328 arg1 stimulation 1378:1388 electrical stimulation 1367:1388 electrical stimulation 1367:1388 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 4 11 theme coaxial 704:710 arg1 electrospinning 712:726 coaxial electrospinning 704:726 coaxial electrospinning 704:726 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 0 12 theme Lycium 91:96 arg1 polysaccharides 107:121 Lycium barbarum polysaccharides 91:121 Lycium barbarum polysaccharides 91:121 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 9 13 theme nerve 1653:1657 arg1 recovery 1659:1666 nerve recovery 1653:1666 nerve recovery 1653:1666 Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery. 37215435 7 14 theme neurons 1287:1293 arg1 growth 1255:1260 directional growth 1243:1260 directional growth 1243:1260 MWCNTs were introduced into the aligned fibers to further increase the electrical conductivity, which promoted the directional growth and neurite extension of neurons in vitro. 37215435 7 14 theme neurons 1287:1293 arg1 extension 1274:1282 neurite extension 1266:1282 neurite extension 1266:1282 MWCNTs were introduced into the aligned fibers to further increase the electrical conductivity, which promoted the directional growth and neurite extension of neurons in vitro. 37215435 2 15 theme nerve 285:289 arg1 alternative 343:353 a potential alternative 331:353 a potential alternative to nerve autografts for the treatment of peripheral nerve injury 331:418 Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. 37215435 2 15 theme nerve 285:289 arg1 conduits 291:298 Biomaterial-based nerve conduits 267:298 Biomaterial-based nerve conduits 267:298 Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. 37215435 4 16 dep Lycium 763:768 arg1 barbarum 770:777 barbarum 770:777 barbarum 770:777 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 4 17 theme growth 739:744 arg1 NGF 754:756 NGF 754:756 NGF 754:756 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 4 17 theme growth 739:744 arg1 factor 746:751 nerve growth factor 733:751 nerve growth factor (NGF) 733:757 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 5 18 theme severe 974:979 arg1 injury 998:1003 severe peripheral nerve injury 974:1003 severe peripheral nerve injury 974:1003 LBP were confirmed to accelerate long-distance axon regeneration after severe peripheral nerve injury. 37215435 3 19 theme guidance 476:483 arg1 mechanisms 536:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 However, an ideal nerve conduit must offer topological guidance and biochemical and electrical signal transduction mechanisms. 37215435 2 20 theme Biomaterial-based 267:283 arg1 alternative 343:353 a potential alternative 331:353 a potential alternative to nerve autografts for the treatment of peripheral nerve injury 331:418 Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. 37215435 2 20 theme Biomaterial-based 267:283 arg1 conduits 291:298 Biomaterial-based nerve conduits 267:298 Biomaterial-based nerve conduits 267:298 Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. 37215435 5 21 theme axon 950:953 arg1 regeneration 955:966 long-distance axon regeneration 936:966 long-distance axon regeneration 936:966 LBP were confirmed to accelerate long-distance axon regeneration after severe peripheral nerve injury. 37215435 1 22 theme more 168:171 arg1 patients 173:180 more and more patients 159:180 more and more patients 159:180 Currently, more and more patients suffer from peripheral nerve injury due to trauma, tumor and other causes worldwide. 37215435 0 23 theme polysaccharides 107:121 arg1 release 80:86 controlled release 69:86 controlled release of Lycium barbarum polysaccharides and nerve growth factor 69:145 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 4 24 theme shell 857:861 arg1 layers 863:868 the core and shell layers 844:868 layers 863:868 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 8 25 theme endogenous 1402:1411 arg1 fields 1422:1427 endogenous electric fields 1402:1427 endogenous electric fields 1402:1427 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 2 26 theme peripheral 396:405 arg1 injury 413:418 peripheral nerve injury 396:418 peripheral nerve injury 396:418 Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. 37215435 8 27 theme fibrous 1344:1350 arg1 scaffolds 1352:1360 conductive fibrous scaffolds 1333:1360 conductive fibrous scaffolds 1333:1360 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 6 28 from promotion 1035:1043 arg1 proliferation 1074:1086 nerve cell proliferation 1063:1086 nerve cell proliferation 1063:1086 In addition, the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth was demonstrated. 37215435 6 28 from promotion 1035:1043 arg1 outgrowth 1100:1108 neurite outgrowth 1092:1108 neurite outgrowth 1092:1108 In addition, the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth was demonstrated. 37215435 7 29 theme neurite 1266:1272 arg1 extension 1274:1282 neurite extension 1266:1282 neurite extension 1266:1282 MWCNTs were introduced into the aligned fibers to further increase the electrical conductivity, which promoted the directional growth and neurite extension of neurons in vitro. 37215435 9 30 theme fiber 1604:1608 arg1 alignment 1610:1618 optimized fiber alignment 1594:1618 optimized fiber alignment 1594:1618 Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery. 37215435 6 31 theme neurite 1092:1098 arg1 outgrowth 1100:1108 neurite outgrowth 1092:1108 neurite outgrowth 1092:1108 In addition, the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth was demonstrated. 37215435 4 32 theme conductive 570:579 arg1 scaffolds 593:601 aligned conductive nanofibrous scaffolds 562:601 aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) 562:682 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 4 33 theme Lycium 763:768 arg1 polysaccharides 779:793 Lycium barbarum polysaccharides 763:793 Lycium barbarum polysaccharides (LBP) purified from the wolfberry 763:827 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 4 33 theme Lycium 763:768 arg1 LBP 796:798 LBP 796:798 LBP 796:798 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 8 34 theme electric 1413:1420 arg1 fields 1422:1427 endogenous electric fields 1402:1427 endogenous electric fields 1402:1427 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 3 35 theme ideal 433:437 arg1 conduit 445:451 an ideal nerve conduit 430:451 an ideal nerve conduit 430:451 However, an ideal nerve conduit must offer topological guidance and biochemical and electrical signal transduction mechanisms. 37215435 0 36 theme cells 20:24 arg1 Regulation 0:9 Regulation 0:9 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 0:146 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 4 37 theme aligned 562:568 arg1 scaffolds 593:601 aligned conductive nanofibrous scaffolds 562:601 aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) 562:682 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 0 38 theme growth 133:138 arg1 factor 140:145 nerve growth factor 127:145 nerve growth factor 127:145 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 8 39 theme PC12 1475:1478 arg1 cells 1480:1484 PC12 cells 1475:1484 PC12 cells 1475:1484 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 5 40 theme peripheral 981:990 arg1 injury 998:1003 severe peripheral nerve injury 974:1003 severe peripheral nerve injury 974:1003 LBP were confirmed to accelerate long-distance axon regeneration after severe peripheral nerve injury. 37215435 1 41 theme peripheral 194:203 arg1 injury 211:216 peripheral nerve injury 194:216 peripheral nerve injury due to trauma, tumor and other causes worldwide 194:264 Currently, more and more patients suffer from peripheral nerve injury due to trauma, tumor and other causes worldwide. 37215435 0 42 theme nerve 14:18 arg1 cells 20:24 nerve cells 14:24 nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor 14:145 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 0 43 theme nerve 127:131 arg1 factor 140:145 nerve growth factor 127:145 nerve growth factor 127:145 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 8 44 theme neurons 1512:1518 arg1 differentiation 1456:1470 the differentiation 1452:1470 the differentiation of PC12 cells 1452:1484 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 8 44 theme neurons 1512:1518 arg1 outgrowth 1499:1507 the axon outgrowth 1490:1507 the axon outgrowth of neurons 1490:1518 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 3 45 theme transduction 523:534 arg1 mechanisms 536:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 However, an ideal nerve conduit must offer topological guidance and biochemical and electrical signal transduction mechanisms. 37215435 1 46 theme nerve 205:209 arg1 injury 211:216 peripheral nerve injury 194:216 peripheral nerve injury due to trauma, tumor and other causes worldwide 194:264 Currently, more and more patients suffer from peripheral nerve injury due to trauma, tumor and other causes worldwide. 37215435 0 47 theme conductive 32:41 arg1 scaffolds 55:63 conductive nanofibrous scaffolds 32:63 conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor 32:145 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 4 48 theme nanofibrous 581:591 arg1 scaffolds 593:601 aligned conductive nanofibrous scaffolds 562:601 aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) 562:682 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 9 49 theme conductive 1561:1570 arg1 fibers 1582:1587 conductive composite fibers 1561:1587 conductive composite fibers with optimized fiber alignment 1561:1618 Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery. 37215435 9 50 theme cell-induced 1537:1548 arg1 behaviors 1550:1558 robust cell-induced behaviors 1530:1558 robust cell-induced behaviors 1530:1558 Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery. 37215435 9 51 theme recovery 1659:1666 arg1 promotion 1640:1648 the promotion 1636:1648 the promotion of nerve recovery 1636:1666 Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery. 37215435 6 52 theme nerve 1063:1067 arg1 proliferation 1074:1086 nerve cell proliferation 1063:1086 nerve cell proliferation 1063:1086 In addition, the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth was demonstrated. 37215435 2 53 theme nerve 407:411 arg1 injury 413:418 peripheral nerve injury 396:418 peripheral nerve injury 396:418 Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. 37215435 0 54 theme factor 140:145 arg1 release 80:86 controlled release 69:86 controlled release of Lycium barbarum polysaccharides and nerve growth factor 69:145 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 6 55 theme synergistic 1023:1033 arg1 promotion 1035:1043 the synergistic promotion 1019:1043 the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth 1019:1108 In addition, the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth was demonstrated. 37215435 5 56 theme long-distance 936:948 arg1 regeneration 955:966 long-distance axon regeneration 936:966 long-distance axon regeneration 936:966 LBP were confirmed to accelerate long-distance axon regeneration after severe peripheral nerve injury. 37215435 9 57 with fibers 1582:1587 arg1 alignment 1610:1618 optimized fiber alignment 1594:1618 optimized fiber alignment 1594:1618 Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery. 37215435 2 58 theme injury 413:418 arg1 treatment 383:391 the treatment 379:391 the treatment of peripheral nerve injury 379:418 Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. 37215435 7 59 theme aligned 1160:1166 arg1 fibers 1168:1173 the aligned fibers 1156:1173 the aligned fibers 1156:1173 MWCNTs were introduced into the aligned fibers to further increase the electrical conductivity, which promoted the directional growth and neurite extension of neurons in vitro. 37215435 3 60 theme signal 516:521 arg1 mechanisms 536:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 However, an ideal nerve conduit must offer topological guidance and biochemical and electrical signal transduction mechanisms. 37215435 1 61 dep trauma 225:230 arg1 worldwide 256:264 worldwide 256:264 worldwide 256:264 Currently, more and more patients suffer from peripheral nerve injury due to trauma, tumor and other causes worldwide. 37215435 8 62 theme cells 1480:1484 arg1 differentiation 1456:1470 the differentiation 1452:1470 the differentiation of PC12 cells 1452:1484 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 8 62 theme cells 1480:1484 arg1 outgrowth 1499:1507 the axon outgrowth 1490:1507 the axon outgrowth of neurons 1490:1518 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 8 63 theme scaffolds 1352:1360 arg1 combination 1318:1328 the combination 1314:1328 the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields 1314:1427 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 0 64 theme nanofibrous 43:53 arg1 scaffolds 55:63 conductive nanofibrous scaffolds 32:63 conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor 32:145 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 9 65 theme composite 1572:1580 arg1 fibers 1582:1587 conductive composite fibers 1561:1587 conductive composite fibers with optimized fiber alignment 1561:1618 Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery. 37215435 4 66 theme core 848:851 arg1 layers 863:868 the core and shell layers 844:868 layers 863:868 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 9 67 theme robust 1530:1535 arg1 behaviors 1550:1558 robust cell-induced behaviors 1530:1558 robust cell-induced behaviors 1530:1558 Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery. 37215435 3 68 theme electrical 505:514 arg1 mechanisms 536:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 However, an ideal nerve conduit must offer topological guidance and biochemical and electrical signal transduction mechanisms. 37215435 3 69 theme nerve 439:443 arg1 conduit 445:451 an ideal nerve conduit 430:451 an ideal nerve conduit 430:451 However, an ideal nerve conduit must offer topological guidance and biochemical and electrical signal transduction mechanisms. 37215435 8 70 theme axon 1494:1497 arg1 outgrowth 1499:1507 the axon outgrowth 1490:1507 the axon outgrowth of neurons 1490:1518 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 9 71 theme optimized 1594:1602 arg1 alignment 1610:1618 optimized fiber alignment 1594:1618 optimized fiber alignment 1594:1618 Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery. 37215435 2 72 theme potential 333:341 arg1 alternative 343:353 a potential alternative 331:353 a potential alternative to nerve autografts for the treatment of peripheral nerve injury 331:418 Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. 37215435 2 72 theme potential 333:341 arg1 conduits 291:298 Biomaterial-based nerve conduits 267:298 Biomaterial-based nerve conduits 267:298 Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. 37215435 4 73 theme carbon 658:663 arg1 MWCNTs 676:681 MWCNTs 676:681 MWCNTs 676:681 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 4 73 theme carbon 658:663 arg1 nanotubes 665:673 multiwalled carbon nanotubes 646:673 multiwalled carbon nanotubes (MWCNTs) 646:682 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 3 74 theme biochemical 489:499 arg1 mechanisms 536:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 However, an ideal nerve conduit must offer topological guidance and biochemical and electrical signal transduction mechanisms. 37215435 4 75 theme multiwalled 646:656 arg1 MWCNTs 676:681 MWCNTs 676:681 MWCNTs 676:681 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 4 75 theme multiwalled 646:656 arg1 nanotubes 665:673 multiwalled carbon nanotubes 646:673 multiwalled carbon nanotubes (MWCNTs) 646:682 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 0 76 theme controlled 69:78 arg1 release 80:86 controlled release 69:86 controlled release of Lycium barbarum polysaccharides and nerve growth factor 69:145 Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor. 37215435 1 77 theme due 218:220 arg1 injury 211:216 peripheral nerve injury 194:216 peripheral nerve injury due to trauma, tumor and other causes worldwide 194:264 Currently, more and more patients suffer from peripheral nerve injury due to trauma, tumor and other causes worldwide. 37215435 3 78 theme topological 464:474 arg1 mechanisms 536:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 topological guidance and biochemical and electrical signal transduction mechanisms 464:545 However, an ideal nerve conduit must offer topological guidance and biochemical and electrical signal transduction mechanisms. 37215435 4 79 theme nerve 733:737 arg1 NGF 754:756 NGF 754:756 NGF 754:756 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 4 79 theme nerve 733:737 arg1 factor 746:751 nerve growth factor 733:751 nerve growth factor (NGF) 733:757 In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. 37215435 8 80 theme conductive 1333:1342 arg1 scaffolds 1352:1360 conductive fibrous scaffolds 1333:1360 conductive fibrous scaffolds 1333:1360 Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. 37215435 6 81 theme LBP 1048:1050 arg1 promotion 1035:1043 the synergistic promotion 1019:1043 the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth 1019:1108 In addition, the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth was demonstrated. 37215435 7 82 theme electrical 1199:1208 arg1 conductivity 1210:1221 the electrical conductivity 1195:1221 the electrical conductivity 1195:1221 MWCNTs were introduced into the aligned fibers to further increase the electrical conductivity, which promoted the directional growth and neurite extension of neurons in vitro. 37215435 6 83 theme NGF 1056:1058 arg1 promotion 1035:1043 the synergistic promotion 1019:1043 the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth 1019:1108 In addition, the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth was demonstrated. 37215435 7 84 theme directional 1243:1253 arg1 growth 1255:1260 directional growth 1243:1260 directional growth 1243:1260 MWCNTs were introduced into the aligned fibers to further increase the electrical conductivity, which promoted the directional growth and neurite extension of neurons in vitro. 36323778 4 0 theme receptor 875:882 arg1 deletion 828:835 deletion 828:835 deletion of the bile acid receptor farnesoid X receptor 828:882 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 7 1 dep allergen- 1233:1241 arg1 inflammation 1271:1282 inflammation 1271:1282 inflammation 1271:1282 Finally, we demonstrate that inulin enhances allergen- and helminth-induced type 2 inflammation. 36323778 1 2 theme fatty 181:185 arg1 acid 187:190 microbially fermented short-chain fatty acid 147:190 microbially fermented short-chain fatty acid metabolites<sup>1,2</sup> 147:228 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 2 3 theme microbiota 485:494 arg1 acids 559:563 bile acids 554:563 bile acids 554:563 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 2 3 theme microbiota 485:494 arg1 levels 504:509 the levels 500:509 the levels of microbiota-derived metabolites 500:543 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 2 3 theme microbiota 485:494 arg1 composition 460:470 the composition 456:470 the composition of the mouse microbiota 456:494 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 4 4 theme X 873:873 arg1 receptor 875:882 the bile acid receptor farnesoid X receptor 840:882 the bile acid receptor farnesoid X receptor 840:882 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 0 5 link microbiota-derived 22:39 arg1 acids 46:50 microbiota-derived bile acids 22:50 microbiota-derived bile acids 22:50 Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation. 36323778 1 6 theme acid 187:190 arg1 metabolites< 192:205 microbially fermented short-chain fatty acid metabolites< 147:205 microbially fermented short-chain fatty acid metabolites<sup>1,2</sup> 147:228 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 8 7 with surfaces 1420:1427 arg1 implications 1434:1445 implications 1434:1445 implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence 1434:1544 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 2 8 theme microbial 363:371 arg1 sequencing 373:382 microbial sequencing 363:382 microbial sequencing 363:382 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 6 9 from enzyme 1092:1097 arg1 species 1116:1122 one bacterial species 1102:1122 one bacterial species 1102:1122 Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. 36323778 4 10 theme acid 772:775 arg1 Delivery 753:760 Delivery 753:760 Delivery of cholic acid 753:775 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 3 11 theme metabolomic 571:581 arg1 shift 583:587 This metabolomic shift 566:587 This metabolomic shift 566:587 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 2 12 theme metabolites 533:543 arg1 acids 559:563 bile acids 554:563 bile acids 554:563 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 2 12 theme metabolites 533:543 arg1 levels 504:509 the levels 500:509 the levels of microbiota-derived metabolites 500:543 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 2 12 theme metabolites 533:543 arg1 composition 460:470 the composition 456:470 the composition of the mouse microbiota 456:494 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 3 13 theme cells 729:733 arg1 eosinophilia 739:750 eosinophilia 739:750 eosinophilia 739:750 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 3 13 theme cells 729:733 arg1 production 679:688 IL-33 production 673:688 IL-33 production 673:688 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 3 13 theme cells 729:733 arg1 activation 691:700 activation 691:700 activation of group 2 innate lymphoid cells 691:733 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 7 14 theme helminth-induced 1247:1262 arg1 type 1264:1267 helminth-induced type 2 1247:1269 helminth-induced type 2 1247:1269 Finally, we demonstrate that inulin enhances allergen- and helminth-induced type 2 inflammation. 36323778 4 15 theme cholic 765:770 arg1 acid 772:775 cholic acid 765:775 cholic acid 765:775 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 3 16 from inflammation 615:626 arg1 lungs 649:653 lungs 649:653 lungs 649:653 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 3 16 from inflammation 615:626 arg1 intestine 635:643 intestine 635:643 intestine 635:643 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 1 17 theme fibre 275:279 arg1 diets 281:285 most fibre diets 270:285 most fibre diets 270:285 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 2 18 theme microbiota-derived 514:531 arg1 metabolites 533:543 microbiota-derived metabolites 514:543 microbiota-derived metabolites 514:543 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 4 19 theme acid 849:852 arg1 receptor 875:882 the bile acid receptor farnesoid X receptor 840:882 the bile acid receptor farnesoid X receptor 840:882 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 4 20 theme inulin-induced 784:797 arg1 inflammation 806:817 inulin-induced type 2 inflammation 784:817 inulin-induced type 2 inflammation 784:817 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 6 21 theme bacterial 1106:1114 arg1 species 1116:1122 one bacterial species 1102:1122 one bacterial species 1102:1122 Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. 36323778 3 22 theme innate 713:718 arg1 cells 729:733 group 2 innate lymphoid cells 705:733 group 2 innate lymphoid cells 705:733 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 4 23 theme bile 844:847 arg1 receptor 875:882 the bile acid receptor farnesoid X receptor 840:882 the bile acid receptor farnesoid X receptor 840:882 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 1 24 theme Dietary 77:83 arg1 fibres 85:90 Dietary fibres 77:90 Dietary fibres 77:90 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 5 25 link human-derived 1008:1020 arg1 microbiota 1022:1031 human-derived microbiota 1008:1031 human-derived microbiota 1008:1031 The effects of inulin are microbiota dependent and were reproduced in mice colonized with human-derived microbiota. 36323778 3 26 theme lymphoid 720:727 arg1 cells 729:733 group 2 innate lymphoid cells 705:733 group 2 innate lymphoid cells 705:733 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 4 27 theme farnesoid 863:871 arg1 receptor 875:882 the bile acid receptor farnesoid X receptor 840:882 the bile acid receptor farnesoid X receptor 840:882 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 6 28 from deletion 1055:1062 arg1 species 1116:1122 one bacterial species 1102:1122 one bacterial species 1102:1122 Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. 36323778 8 29 theme barrier 1412:1418 arg1 surfaces 1420:1427 barrier surfaces 1412:1427 barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence 1412:1544 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 6 30 theme genetic 1047:1053 arg1 deletion 1055:1062 genetic deletion 1047:1062 genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species 1047:1122 Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. 36323778 1 31 theme diets 281:285 arg1 roles 261:265 the immunoregulatory roles 240:265 the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites 240:326 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 4 32 theme receptor 854:861 arg1 receptor 875:882 the bile acid receptor farnesoid X receptor 840:882 the bile acid receptor farnesoid X receptor 840:882 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 6 33 theme enzyme 1092:1097 arg1 deletion 1055:1062 genetic deletion 1047:1062 genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species 1047:1122 Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. 36323778 2 34 theme fibre 443:447 arg1 diet 428:431 a diet 426:431 a diet of inulin fibre 426:447 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 8 35 theme inflammation 1497:1508 arg1 pathophysiology 1469:1483 the pathophysiology 1465:1483 the pathophysiology of allergic inflammation, tissue protection and host defence 1465:1544 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 5 36 theme inulin 933:938 arg1 dependent 955:963 dependent 955:963 dependent 955:963 The effects of inulin are microbiota dependent and were reproduced in mice colonized with human-derived microbiota. 36323778 5 36 theme inulin 933:938 arg1 effects 922:928 The effects 918:928 The effects of inulin 918:938 The effects of inulin are microbiota dependent and were reproduced in mice colonized with human-derived microbiota. 36323778 8 37 theme cholic 1373:1378 arg1 acid 1380:1383 microbiota-derived cholic acid 1354:1383 microbiota-derived cholic acid 1354:1383 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 6 38 theme bile-acid-metabolizing 1069:1090 arg1 enzyme 1092:1097 a bile-acid-metabolizing enzyme 1067:1097 a bile-acid-metabolizing enzyme in one bacterial species 1067:1122 Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. 36323778 6 39 from species 1116:1122 arg1 deletion 1055:1062 genetic deletion 1047:1062 genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species 1047:1122 Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. 36323778 8 40 theme tissue 1511:1516 arg1 protection 1518:1527 tissue protection 1511:1527 tissue protection 1511:1527 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 1 41 theme beneficial 102:111 arg1 effects 131:137 beneficial anti-inflammatory effects 102:137 beneficial anti-inflammatory effects 102:137 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 2 42 theme untargeted 388:397 arg1 metabolomics 399:410 untargeted metabolomics 388:410 untargeted metabolomics 388:410 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 2 43 theme mouse 479:483 arg1 microbiota 485:494 the mouse microbiota 475:494 the mouse microbiota 475:494 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 1 44 theme microbiota-derived 297:314 arg1 metabolites 316:326 their microbiota-derived metabolites 291:326 their microbiota-derived metabolites 291:326 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 2 45 theme bile 554:557 arg1 acids 559:563 bile acids 554:563 bile acids 554:563 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 3 46 theme type 608:611 arg1 inflammation 615:626 type 2 inflammation 608:626 type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia 608:750 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 0 47 theme bile 41:44 arg1 acids 46:50 microbiota-derived bile acids 22:50 microbiota-derived bile acids 22:50 Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation. 36323778 1 48 theme metabolites 316:326 arg1 roles 261:265 the immunoregulatory roles 240:265 the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites 240:326 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 0 49 theme microbiota-derived 22:39 arg1 acids 46:50 microbiota-derived bile acids 22:50 microbiota-derived bile acids 22:50 Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation. 36323778 3 50 dep intestine 635:643 arg1 the 631:633 the 631:633 the 631:633 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 0 51 theme type 56:59 arg1 inflammation 63:74 type 2 inflammation 56:74 type 2 inflammation 56:74 Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation. 36323778 8 52 theme type 1389:1392 arg1 inflammation 1396:1407 microbiota-derived cholic acid and type 2 inflammation 1354:1407 microbiota-derived cholic acid and type 2 inflammation 1354:1407 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 8 53 theme protection 1518:1527 arg1 pathophysiology 1469:1483 the pathophysiology 1465:1483 the pathophysiology of allergic inflammation, tissue protection and host defence 1465:1544 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 1 54 dep metabolites< 192:205 arg1 sup> 207:212 sup> 207:212 microbially fermented short-chain fatty acid metabolites<sup>1,2</sup> 147:228 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 1 54 dep metabolites< 192:205 arg1 /sup> 221:227 /sup> 221:227 microbially fermented short-chain fatty acid metabolites<sup>1,2</sup> 147:228 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 1 54 dep metabolites< 192:205 arg1 1,2< 214:219 1,2< 214:219 microbially fermented short-chain fatty acid metabolites<sup>1,2</sup> 147:228 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 8 55 link microbiota-derived 1354:1371 arg1 acid 1380:1383 microbiota-derived cholic acid 1354:1383 microbiota-derived cholic acid 1354:1383 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 1 56 theme anti-inflammatory 113:129 arg1 effects 131:137 beneficial anti-inflammatory effects 102:137 beneficial anti-inflammatory effects 102:137 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 8 57 theme defence 1538:1544 arg1 pathophysiology 1469:1483 the pathophysiology 1465:1483 the pathophysiology of allergic inflammation, tissue protection and host defence 1465:1544 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 8 58 theme microbiota-derived 1354:1371 arg1 acid 1380:1383 microbiota-derived cholic acid 1354:1383 microbiota-derived cholic acid 1354:1383 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 8 59 theme host 1533:1536 arg1 defence 1538:1544 host defence 1533:1544 host defence 1533:1544 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 6 60 theme inulin 1149:1154 arg1 ability 1138:1144 the ability 1134:1144 the ability of inulin to trigger type 2 inflammation 1134:1185 Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. 36323778 6 61 theme type 1167:1170 arg1 inflammation 1174:1185 type 2 inflammation 1167:1185 type 2 inflammation 1167:1185 Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. 36323778 4 62 theme inulin 910:915 arg1 effects 899:905 the effects 895:905 the effects of inulin 895:915 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 4 63 theme type 799:802 arg1 inflammation 806:817 inulin-induced type 2 inflammation 784:817 inulin-induced type 2 inflammation 784:817 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 2 64 link microbiota-derived 514:531 arg1 metabolites 533:543 microbiota-derived metabolites 514:543 microbiota-derived metabolites 514:543 Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. 36323778 4 65 dep mimics 777:782 arg1 whereas 820:826 whereas 820:826 whereas 820:826 Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. 36323778 8 66 theme acid 1380:1383 arg1 inflammation 1396:1407 microbiota-derived cholic acid and type 2 inflammation 1354:1407 microbiota-derived cholic acid and type 2 inflammation 1354:1407 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 3 67 theme IL-33 673:677 arg1 production 679:688 IL-33 production 673:688 IL-33 production 673:688 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 5 68 theme human-derived 1008:1020 arg1 microbiota 1022:1031 human-derived microbiota 1008:1031 human-derived microbiota 1008:1031 The effects of inulin are microbiota dependent and were reproduced in mice colonized with human-derived microbiota. 36323778 1 69 link microbiota-derived 297:314 arg1 metabolites 316:326 their microbiota-derived metabolites 291:326 their microbiota-derived metabolites 291:326 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 1 70 theme fermented 159:167 arg1 acid 187:190 microbially fermented short-chain fatty acid 147:190 microbially fermented short-chain fatty acid metabolites<sup>1,2</sup> 147:228 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 3 71 theme group 705:709 arg1 cells 729:733 group 2 innate lymphoid cells 705:733 group 2 innate lymphoid cells 705:733 This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. 36323778 8 72 theme allergic 1488:1495 arg1 inflammation 1497:1508 allergic inflammation 1488:1508 allergic inflammation 1488:1508 Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. 36323778 1 73 theme short-chain 169:179 arg1 acid 187:190 microbially fermented short-chain fatty acid 147:190 microbially fermented short-chain fatty acid metabolites<sup>1,2</sup> 147:228 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36323778 1 74 theme immunoregulatory 244:259 arg1 roles 261:265 the immunoregulatory roles 240:265 the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites 240:326 Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. 36852467 0 0 theme Cell 96:99 arg1 Fate 101:104 Mouse Embryonic Stem Cell Fate 75:104 Mouse Embryonic Stem Cell Fate 75:104 Chemoproteomic and Transcriptomic Analysis Reveals that O-GlcNAc Regulates Mouse Embryonic Stem Cell Fate through the Pluripotency Network. 36852467 4 1 theme neuronal 687:694 arg1 lineage 696:702 the neuronal lineage 683:702 the neuronal lineage 683:702 Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. 36852467 4 2 from sites 739:743 arg1 PTFs-was 782:789 PTFs-was 782:789 PTFs-was found to decline 782:806 Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. 36852467 4 2 from sites 739:743 arg1 stoichiometry 718:730 the O-GlcNAc stoichiometry 705:730 the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which 705:775 Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. 36852467 1 3 theme embryonic 176:184 arg1 ESCs 198:201 ESCs 198:201 ESCs 198:201 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36852467 1 3 theme embryonic 176:184 arg1 cells 191:195 embryonic stem cells 176:195 embryonic stem cells (ESCs) 176:202 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36852467 0 4 theme Stem 91:94 arg1 Fate 101:104 Mouse Embryonic Stem Cell Fate 75:104 Mouse Embryonic Stem Cell Fate 75:104 Chemoproteomic and Transcriptomic Analysis Reveals that O-GlcNAc Regulates Mouse Embryonic Stem Cell Fate through the Pluripotency Network. 36852467 1 5 theme stem 186:189 arg1 ESCs 198:201 ESCs 198:201 ESCs 198:201 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36852467 1 5 theme stem 186:189 arg1 cells 191:195 embryonic stem cells 176:195 embryonic stem cells (ESCs) 176:202 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36852467 6 6 theme PTF 998:1000 arg1 network 1002:1008 the core PTF network 989:1008 the core PTF network 989:1008 By acting on the core PTF network, suppression of O-GlcNAcylation upregulates neuron-related genes, thus contributing to the mESC fate determination. 36852467 6 7 theme fate 1106:1109 arg1 determination 1111:1123 the mESC fate determination 1097:1123 the mESC fate determination 1097:1123 By acting on the core PTF network, suppression of O-GlcNAcylation upregulates neuron-related genes, thus contributing to the mESC fate determination. 36852467 3 8 theme core 540:543 arg1 factor 572:577 third core pluripotency transcription factor 534:577 the third core pluripotency transcription factor (PTF) NANOG 530:589 In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. 36852467 3 8 theme core 540:543 arg1 PTF 580:582 PTF 580:582 PTF 580:582 In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. 36852467 5 9 theme PTFs 970:973 arg1 901 941:943 901 941:943 901 941:943 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 5 9 theme PTFs 970:973 arg1 genes 956:960 target genes 949:960 target genes of core PTFs 949:973 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 6 10 theme core 993:996 arg1 network 1002:1008 the core PTF network 989:1008 the core PTF network 989:1008 By acting on the core PTF network, suppression of O-GlcNAcylation upregulates neuron-related genes, thus contributing to the mESC fate determination. 36852467 4 11 theme proteins-several 751:766 arg1 sites 739:743 123 sites 735:743 123 sites of 83 proteins-several of which 735:775 Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. 36852467 4 11 theme proteins-several 751:766 arg1 proteins-several 751:766 83 proteins-several 748:766 83 proteins-several of which 748:775 Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. 36852467 3 12 theme pluripotency 545:556 arg1 factor 572:577 third core pluripotency transcription factor 534:577 the third core pluripotency transcription factor (PTF) NANOG 530:589 In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. 36852467 3 12 theme pluripotency 545:556 arg1 PTF 580:582 PTF 580:582 PTF 580:582 In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. 36852467 5 13 theme responsive 879:888 arg1 genes 873:877 2,456 differentially expressed genes 842:877 2,456 differentially expressed genes responsive to OGT inhibition 842:906 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 0 14 theme Pluripotency 118:129 arg1 Network 131:137 the Pluripotency Network 114:137 the Pluripotency Network 114:137 Chemoproteomic and Transcriptomic Analysis Reveals that O-GlcNAc Regulates Mouse Embryonic Stem Cell Fate through the Pluripotency Network. 36852467 6 15 theme O-GlcNAcylation 1026:1040 arg1 suppression 1011:1021 suppression 1011:1021 suppression of O-GlcNAcylation 1011:1040 By acting on the core PTF network, suppression of O-GlcNAcylation upregulates neuron-related genes, thus contributing to the mESC fate determination. 36852467 1 16 theme cells 191:195 arg1 Self-renewal 140:151 Self-renewal 140:151 Self-renewal 140:151 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36852467 3 17 theme third 534:538 arg1 factor 572:577 third core pluripotency transcription factor 534:577 the third core pluripotency transcription factor (PTF) NANOG 530:589 In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. 36852467 3 17 theme third 534:538 arg1 PTF 580:582 PTF 580:582 PTF 580:582 In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. 36852467 6 18 theme mESC 1101:1104 arg1 determination 1111:1123 the mESC fate determination 1097:1123 the mESC fate determination 1097:1123 By acting on the core PTF network, suppression of O-GlcNAcylation upregulates neuron-related genes, thus contributing to the mESC fate determination. 36852467 2 19 theme 1,340 418:422 arg1 sites 437:441 1,340 modification sites 418:441 1,340 modification sites 418:441 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 2 20 from identification 368:381 arg1 mESCs 458:462 mESCs 458:462 mESCs 458:462 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 2 20 from identification 368:381 arg1 ESCs 452:455 mouse ESCs 446:455 mouse ESCs (mESCs) 446:463 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 5 21 theme OGT 893:895 arg1 inhibition 897:906 OGT inhibition 893:906 OGT inhibition 893:906 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 0 22 theme Chemoproteomic 0:13 arg1 Analysis 34:41 Chemoproteomic and Transcriptomic Analysis 0:41 Chemoproteomic and Transcriptomic Analysis 0:41 Chemoproteomic and Transcriptomic Analysis Reveals that O-GlcNAc Regulates Mouse Embryonic Stem Cell Fate through the Pluripotency Network. 36852467 1 23 link O-linked 230:237 arg1 modification 272:283 protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification 222:283 protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification 222:283 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36852467 5 24 theme Transcriptomic 809:822 arg1 profiling 824:832 Transcriptomic profiling 809:832 Transcriptomic profiling 809:832 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 2 25 theme proteins 405:412 arg1 identification 368:381 the identification 364:381 the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) 364:463 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 1 26 theme underlying 294:303 arg1 mechanism 305:313 the underlying mechanism 290:313 the underlying mechanism 290:313 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36852467 3 27 theme transcription 558:570 arg1 factor 572:577 third core pluripotency transcription factor 534:577 the third core pluripotency transcription factor (PTF) NANOG 530:589 In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. 36852467 3 27 theme transcription 558:570 arg1 PTF 580:582 PTF 580:582 PTF 580:582 In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. 36852467 0 28 theme Transcriptomic 19:32 arg1 Analysis 34:41 Chemoproteomic and Transcriptomic Analysis 0:41 Chemoproteomic and Transcriptomic Analysis 0:41 Chemoproteomic and Transcriptomic Analysis Reveals that O-GlcNAc Regulates Mouse Embryonic Stem Cell Fate through the Pluripotency Network. 36852467 3 29 theme factor 572:577 arg1 NANOG 585:589 the third core pluripotency transcription factor (PTF) NANOG 530:589 the third core pluripotency transcription factor (PTF) NANOG 530:589 In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. 36852467 2 30 theme mouse 446:450 arg1 mESCs 458:462 mESCs 458:462 mESCs 458:462 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 2 30 theme mouse 446:450 arg1 ESCs 452:455 mouse ESCs 446:455 mouse ESCs (mESCs) 446:463 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 6 31 theme neuron-related 1054:1067 arg1 genes 1069:1073 neuron-related genes 1054:1073 neuron-related genes 1054:1073 By acting on the core PTF network, suppression of O-GlcNAcylation upregulates neuron-related genes, thus contributing to the mESC fate determination. 36852467 5 32 theme expressed 863:871 arg1 genes 873:877 2,456 differentially expressed genes 842:877 2,456 differentially expressed genes responsive to OGT inhibition 842:906 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 2 33 theme chemoproteomics 476:490 arg1 method 492:497 a chemoproteomics method 474:497 a chemoproteomics method 474:497 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 1 34 theme protein 222:228 arg1 modification 272:283 protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification 222:283 protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification 222:283 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36852467 2 35 from proteins 405:412 arg1 mESCs 458:462 mESCs 458:462 mESCs 458:462 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 2 35 from proteins 405:412 arg1 ESCs 452:455 mouse ESCs 446:455 mouse ESCs (mESCs) 446:463 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 4 36 theme O-GlcNAc 709:716 arg1 PTFs-was 782:789 PTFs-was 782:789 PTFs-was found to decline 782:806 Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. 36852467 4 36 theme O-GlcNAc 709:716 arg1 stoichiometry 718:730 the O-GlcNAc stoichiometry 705:730 the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which 705:775 Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. 36852467 2 37 theme modification 424:435 arg1 sites 437:441 1,340 modification sites 418:441 1,340 modification sites 418:441 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 5 38 theme core 965:968 arg1 PTFs 970:973 core PTFs 965:973 core PTFs 965:973 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 1 39 theme O-linked 230:237 arg1 modification 272:283 protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification 222:283 protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification 222:283 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36852467 4 40 theme which 771:775 arg1 proteins-several 751:766 83 proteins-several 748:766 83 proteins-several of which 748:775 Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. 36852467 5 41 theme target 949:954 arg1 901 941:943 901 941:943 901 941:943 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 5 41 theme target 949:954 arg1 genes 956:960 target genes 949:960 target genes of core PTFs 949:973 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 1 42 theme β-N-acetylglucosamine 239:259 arg1 modification 272:283 protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification 222:283 protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification 222:283 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36852467 0 43 theme Embryonic 81:89 arg1 Fate 101:104 Mouse Embryonic Stem Cell Fate 75:104 Mouse Embryonic Stem Cell Fate 75:104 Chemoproteomic and Transcriptomic Analysis Reveals that O-GlcNAc Regulates Mouse Embryonic Stem Cell Fate through the Pluripotency Network. 36852467 2 44 theme sites 437:441 arg1 identification 368:381 the identification 364:381 the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) 364:463 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 2 45 from sites 437:441 arg1 mESCs 458:462 mESCs 458:462 mESCs 458:462 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 2 45 from sites 437:441 arg1 ESCs 452:455 mouse ESCs 446:455 mouse ESCs (mESCs) 446:463 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 2 46 theme O-GlcNAcylated 390:403 arg1 proteins 405:412 979 O-GlcNAcylated proteins 386:412 979 O-GlcNAcylated proteins 386:412 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 0 47 theme Mouse 75:79 arg1 Fate 101:104 Mouse Embryonic Stem Cell Fate 75:104 Mouse Embryonic Stem Cell Fate 75:104 Chemoproteomic and Transcriptomic Analysis Reveals that O-GlcNAc Regulates Mouse Embryonic Stem Cell Fate through the Pluripotency Network. 36852467 2 48 from ESCs 452:455 arg1 identification 368:381 the identification 364:381 the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) 364:463 Here, we report the identification of 979 O-GlcNAcylated proteins and 1,340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. 36852467 5 49 theme differentiation 915:929 arg1 901 941:943 901 941:943 901 941:943 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 5 49 theme differentiation 915:929 arg1 genes 956:960 target genes 949:960 target genes of core PTFs 949:973 Transcriptomic profiling reveals 2,456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. 36852467 1 50 theme O-GlcNAc 262:269 arg1 modification 272:283 protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification 222:283 protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification 222:283 Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. 36811005 2 0 with function 400:407 arg1 accumulation 567:578 active component accumulation 550:578 active component accumulation 550:578 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 6 1 from abundances 1193:1202 arg1 structure 1166:1174 their structure 1160:1174 their structure 1160:1174 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 1 2 theme high 269:272 arg1 materials 292:300 high quality medicinal materials 269:300 high quality medicinal materials 269:300 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 0 3 theme components 182:191 arg1 accumulation 159:170 the accumulation 155:170 the accumulation of active components 155:191 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 7 4 from contents 1242:1249 arg1 RAM 1283:1285 wild RAM 1278:1285 wild RAM 1278:1285 Meanwhile, the contents of effective components in wild RAM were significantly higher than those in cultivated RAM. 36811005 2 5 from relationships 531:543 arg1 cultivated 469:478 cultivated 469:478 cultivated 469:478 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 5 from relationships 531:543 arg1 wild 460:463 wild 460:463 wild 460:463 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 1 6 theme quality 274:280 arg1 materials 292:300 high quality medicinal materials 269:300 high quality medicinal materials 269:300 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 0 7 from Diversity 0:8 arg1 effects 144:150 their effects 138:150 their effects on the accumulation of active components 138:191 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 0 7 from Diversity 0:8 arg1 accumulation 159:170 the accumulation 155:170 the accumulation of active components 155:191 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 0 7 from Diversity 0:8 arg1 Macrocephalae 120:132 Macrocephalae 120:132 Macrocephalae 120:132 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 4 8 theme classes 907:913 arg1 total 885:889 A total 883:889 A total of 24 phyla, 46 classes, and 110 genera 883:929 A total of 24 phyla, 46 classes, and 110 genera were detected. 36811005 5 9 theme dominant 950:957 arg1 taxa 959:962 The dominant taxa 946:962 The dominant taxa 946:962 The dominant taxa were Proteobacteria, Ascomycota, and Basidiomycota. 36811005 5 9 theme dominant 950:957 arg1 Proteobacteria 969:982 Proteobacteria 969:982 Proteobacteria 969:982 The dominant taxa were Proteobacteria, Ascomycota, and Basidiomycota. 36811005 0 10 from accumulation 159:170 arg1 Diversity 0:8 Diversity 0:8 Diversity 0:8 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 0 10 from accumulation 159:170 arg1 analysis 25:32 structural analysis 14:32 structural analysis 14:32 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 6 11 theme microorganism 1207:1219 arg1 taxa 1221:1224 microorganism taxa 1207:1224 microorganism taxa 1207:1224 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 2 12 from composition 372:382 arg1 cultivated 469:478 cultivated 469:478 cultivated 469:478 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 12 from composition 372:382 arg1 wild 460:463 wild 460:463 wild 460:463 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 8 13 theme Correlation 1343:1353 arg1 analysis 1355:1362 Correlation analysis 1343:1362 Correlation analysis 1343:1362 Correlation analysis showed that 16 bacterial and 10 fungal genera were positively or negatively correlated with active ingredient accumulation. 36811005 3 14 with diversity 725:733 arg1 accumulation 806:817 the accumulation 802:817 the accumulation of polysaccharides, atractylone, and lactones 802:863 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 1 15 theme materials 292:300 arg1 formation 256:264 the formation 252:264 the formation of high quality medicinal materials 252:300 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 2 16 theme component 557:565 arg1 accumulation 567:578 active component accumulation 550:578 active component accumulation 550:578 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 17 dep cultivated 469:478 arg1 RAM 516:518 RAM 516:518 RAM 516:518 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 17 dep cultivated 469:478 arg1 Macrocephalae 501:513 Macrocephalae 501:513 Macrocephalae 501:513 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 18 with relationships 531:543 arg1 accumulation 567:578 active component accumulation 550:578 active component accumulation 550:578 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 19 theme microbial 424:432 arg1 communities 434:444 rhizosphere microbial communities 412:444 rhizosphere microbial communities 412:444 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 20 theme active 550:555 arg1 accumulation 567:578 active component accumulation 550:578 active component accumulation 550:578 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 3 21 theme RAM 765:767 arg1 species 769:775 three RAM species 759:775 three RAM species 759:775 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 3 22 dep diversity 725:733 arg1 fungi 749:753 fungi 749:753 fungi 749:753 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 3 22 dep diversity 725:733 arg1 bacteria 736:743 bacteria 736:743 bacteria 736:743 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 2 23 from diversity 385:393 arg1 cultivated 469:478 cultivated 469:478 cultivated 469:478 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 23 from diversity 385:393 arg1 wild 460:463 wild 460:463 wild 460:463 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 24 theme rhizosphere 412:422 arg1 communities 434:444 rhizosphere microbial communities 412:444 rhizosphere microbial communities 412:444 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 3 25 theme species 769:775 arg1 correlation 785:795 its correlation 781:795 its correlation with the accumulation of polysaccharides, atractylone, and lactones 781:863 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 3 25 theme species 769:775 arg1 diversity 725:733 the rhizosphere microbial community diversity 689:733 the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species 689:775 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 6 26 from communities 1030:1040 arg1 samples 1088:1094 both wild and artificially cultivated soil samples 1045:1094 both wild and artificially cultivated soil samples 1045:1094 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 7 27 theme wild 1278:1281 arg1 RAM 1283:1285 wild RAM 1278:1285 wild RAM 1278:1285 Meanwhile, the contents of effective components in wild RAM were significantly higher than those in cultivated RAM. 36811005 1 28 theme Rhizosphere 194:204 arg1 microorganisms 206:219 Rhizosphere microorganisms 194:219 Rhizosphere microorganisms 194:219 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 1 28 theme Rhizosphere 194:204 arg1 factors 234:240 the main factors 225:240 the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites 225:356 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 7 29 from RAM 1283:1285 arg1 Meanwhile 1227:1235 Meanwhile 1227:1235 Meanwhile 1227:1235 Meanwhile, the contents of effective components in wild RAM were significantly higher than those in cultivated RAM. 36811005 7 29 from RAM 1283:1285 arg1 contents 1242:1249 the contents 1238:1249 the contents of effective components in wild RAM 1238:1285 Meanwhile, the contents of effective components in wild RAM were significantly higher than those in cultivated RAM. 36811005 3 30 theme high-throughput 618:632 arg1 sequencing 634:643 high-throughput sequencing 618:643 high-throughput sequencing 618:643 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 6 31 from differences 1145:1155 arg1 structure 1166:1174 their structure 1160:1174 their structure 1160:1174 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 7 32 theme cultivated 1327:1336 arg1 RAM 1338:1340 cultivated RAM 1327:1340 cultivated RAM 1327:1340 Meanwhile, the contents of effective components in wild RAM were significantly higher than those in cultivated RAM. 36811005 7 33 from components 1264:1273 arg1 RAM 1283:1285 wild RAM 1278:1285 wild RAM 1278:1285 Meanwhile, the contents of effective components in wild RAM were significantly higher than those in cultivated RAM. 36811005 9 34 theme future 1627:1632 arg1 research 1634:1641 future research 1627:1641 future research on endangered materials 1627:1665 These results showed that rhizosphere microorganisms could play an important role in component accumulation and might lay a foundation for future research on endangered materials. 36811005 6 35 theme wild 1050:1053 arg1 samples 1088:1094 both wild and artificially cultivated soil samples 1045:1094 both wild and artificially cultivated soil samples 1045:1094 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 0 36 theme structural 14:23 arg1 analysis 25:32 structural analysis 14:32 structural analysis 14:32 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 6 37 theme relative 1184:1191 arg1 abundances 1193:1202 the relative abundances 1180:1202 the relative abundances of microorganism taxa 1180:1224 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 3 38 theme microbial 705:713 arg1 diversity 725:733 the rhizosphere microbial community diversity 689:733 the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species 689:775 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 9 39 from research 1634:1641 arg1 materials 1657:1665 endangered materials 1646:1665 endangered materials 1646:1665 These results showed that rhizosphere microorganisms could play an important role in component accumulation and might lay a foundation for future research on endangered materials. 36811005 7 40 theme effective 1254:1262 arg1 components 1264:1273 effective components 1254:1273 effective components in wild RAM 1254:1285 Meanwhile, the contents of effective components in wild RAM were significantly higher than those in cultivated RAM. 36811005 0 41 theme rhizosphere 37:47 arg1 communities 64:74 rhizosphere soil microbial communities 37:74 rhizosphere soil microbial communities 37:74 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 4 42 theme genera 924:929 arg1 total 885:889 A total 883:889 A total of 24 phyla, 46 classes, and 110 genera 883:929 A total of 24 phyla, 46 classes, and 110 genera were detected. 36811005 3 43 theme community 715:723 arg1 diversity 725:733 the rhizosphere microbial community diversity 689:733 the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species 689:775 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 3 44 theme correlation 649:659 arg1 analysis 661:668 correlation analysis 649:668 correlation analysis 649:668 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 8 45 dep 16 1376:1377 arg1 bacterial 1379:1387 bacterial 1379:1387 bacterial 1379:1387 Correlation analysis showed that 16 bacterial and 10 fungal genera were positively or negatively correlated with active ingredient accumulation. 36811005 8 45 dep 16 1376:1377 arg1 genera 1403:1408 fungal genera 1396:1408 fungal genera 1396:1408 Correlation analysis showed that 16 bacterial and 10 fungal genera were positively or negatively correlated with active ingredient accumulation. 36811005 1 46 theme main 229:232 arg1 microorganisms 206:219 Rhizosphere microorganisms 194:219 Rhizosphere microorganisms 194:219 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 1 46 theme main 229:232 arg1 factors 234:240 the main factors 225:240 the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites 225:356 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 6 47 theme soil 1083:1086 arg1 samples 1088:1094 both wild and artificially cultivated soil samples 1045:1094 both wild and artificially cultivated soil samples 1045:1094 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 2 48 with composition 372:382 arg1 accumulation 567:578 active component accumulation 550:578 active component accumulation 550:578 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 8 49 theme fungal 1396:1401 arg1 genera 1403:1408 fungal genera 1396:1408 fungal genera 1396:1408 Correlation analysis showed that 16 bacterial and 10 fungal genera were positively or negatively correlated with active ingredient accumulation. 36811005 2 50 theme communities 434:444 arg1 relationships 531:543 their relationships 525:543 their relationships with active component accumulation 525:578 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 50 theme communities 434:444 arg1 diversity 385:393 diversity 385:393 diversity 385:393 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 50 theme communities 434:444 arg1 function 400:407 function 400:407 function 400:407 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 50 theme communities 434:444 arg1 composition 372:382 composition 372:382 composition 372:382 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 0 51 theme microbial 54:62 arg1 communities 64:74 rhizosphere soil microbial communities 37:74 rhizosphere soil microbial communities 37:74 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 1 52 theme secondary 336:344 arg1 metabolites 346:356 secondary metabolites 336:356 secondary metabolites 336:356 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 0 53 theme communities 64:74 arg1 Diversity 0:8 Diversity 0:8 Diversity 0:8 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 0 53 theme communities 64:74 arg1 analysis 25:32 structural analysis 14:32 structural analysis 14:32 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 2 54 from function 400:407 arg1 cultivated 469:478 cultivated 469:478 cultivated 469:478 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 2 54 from function 400:407 arg1 wild 460:463 wild 460:463 wild 460:463 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 9 55 theme rhizosphere 1514:1524 arg1 microorganisms 1526:1539 rhizosphere microorganisms 1514:1539 rhizosphere microorganisms 1514:1539 These results showed that rhizosphere microorganisms could play an important role in component accumulation and might lay a foundation for future research on endangered materials. 36811005 0 56 theme soil 49:52 arg1 communities 64:74 rhizosphere soil microbial communities 37:74 rhizosphere soil microbial communities 37:74 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 1 57 theme metabolites 346:356 arg1 accumulation 320:331 the accumulation 316:331 the accumulation of secondary metabolites 316:356 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 4 58 theme phyla 897:901 arg1 total 885:889 A total 883:889 A total of 24 phyla, 46 classes, and 110 genera 883:929 A total of 24 phyla, 46 classes, and 110 genera were detected. 36811005 2 59 with diversity 385:393 arg1 accumulation 567:578 active component accumulation 550:578 active component accumulation 550:578 However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. 36811005 9 60 theme endangered 1646:1655 arg1 materials 1657:1665 endangered materials 1646:1665 endangered materials 1646:1665 These results showed that rhizosphere microorganisms could play an important role in component accumulation and might lay a foundation for future research on endangered materials. 36811005 8 61 theme active 1456:1461 arg1 accumulation 1474:1485 active ingredient accumulation 1456:1485 active ingredient accumulation 1456:1485 Correlation analysis showed that 16 bacterial and 10 fungal genera were positively or negatively correlated with active ingredient accumulation. 36811005 3 62 theme polysaccharides 822:836 arg1 accumulation 806:817 the accumulation 802:817 the accumulation of polysaccharides, atractylone, and lactones 802:863 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 0 63 theme active 175:180 arg1 components 182:191 active components 175:191 active components 175:191 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 3 64 with correlation 785:795 arg1 accumulation 806:817 the accumulation 802:817 the accumulation of polysaccharides, atractylone, and lactones 802:863 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 6 65 theme taxa 1221:1224 arg1 abundances 1193:1202 the relative abundances 1180:1202 the relative abundances of microorganism taxa 1180:1224 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 6 65 theme taxa 1221:1224 arg1 differences 1145:1155 some differences 1140:1155 some differences in their structure 1140:1174 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 9 66 theme important 1555:1563 arg1 role 1565:1568 an important role 1552:1568 an important role 1552:1568 These results showed that rhizosphere microorganisms could play an important role in component accumulation and might lay a foundation for future research on endangered materials. 36811005 3 67 theme rhizosphere 693:703 arg1 diversity 725:733 the rhizosphere microbial community diversity 689:733 the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species 689:775 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 9 68 theme component 1573:1581 arg1 accumulation 1583:1594 component accumulation 1573:1594 component accumulation 1573:1594 These results showed that rhizosphere microorganisms could play an important role in component accumulation and might lay a foundation for future research on endangered materials. 36811005 3 69 theme lactones 856:863 arg1 accumulation 806:817 the accumulation 802:817 the accumulation of polysaccharides, atractylone, and lactones 802:863 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 8 70 theme ingredient 1463:1472 arg1 accumulation 1474:1485 active ingredient accumulation 1456:1485 active ingredient accumulation 1456:1485 Correlation analysis showed that 16 bacterial and 10 fungal genera were positively or negatively correlated with active ingredient accumulation. 36811005 1 71 dep factors 234:240 arg1 affecting 242:250 affecting 242:250 affecting the formation of high quality medicinal materials 242:300 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 1 71 dep factors 234:240 arg1 promoting 306:314 promoting 306:314 promoting the accumulation of secondary metabolites 306:356 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 7 72 theme components 1264:1273 arg1 Meanwhile 1227:1235 Meanwhile 1227:1235 Meanwhile 1227:1235 Meanwhile, the contents of effective components in wild RAM were significantly higher than those in cultivated RAM. 36811005 7 72 theme components 1264:1273 arg1 contents 1242:1249 the contents 1238:1249 the contents of effective components in wild RAM 1238:1285 Meanwhile, the contents of effective components in wild RAM were significantly higher than those in cultivated RAM. 36811005 0 73 from effects 144:150 arg1 accumulation 159:170 the accumulation 155:170 the accumulation of active components 155:191 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 3 74 dep study 683:687 arg1 II 869:870 II 869:870 II 869:870 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 3 74 dep study 683:687 arg1 III 877:879 III 877:879 III 877:879 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 3 75 used used 675:678 arg2 sequencing 634:643 high-throughput sequencing 618:643 high-throughput sequencing 618:643 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 3 75 used used 675:678 arg2 analysis 661:668 correlation analysis 649:668 correlation analysis 649:668 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36811005 6 76 theme cultivated 1072:1081 arg1 samples 1088:1094 both wild and artificially cultivated soil samples 1045:1094 both wild and artificially cultivated soil samples 1045:1094 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 1 77 theme medicinal 282:290 arg1 materials 292:300 high quality medicinal materials 269:300 high quality medicinal materials 269:300 Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. 36811005 0 78 from analysis 25:32 arg1 effects 144:150 their effects 138:150 their effects on the accumulation of active components 138:191 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 0 78 from analysis 25:32 arg1 accumulation 159:170 the accumulation 155:170 the accumulation of active components 155:191 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 0 78 from analysis 25:32 arg1 Macrocephalae 120:132 Macrocephalae 120:132 Macrocephalae 120:132 Diversity and structural analysis of rhizosphere soil microbial communities in wild and cultivated Rhizoma Atractylodis Macrocephalae and their effects on the accumulation of active components. 36811005 6 79 theme microbial 1020:1028 arg1 communities 1030:1040 The microbial communities 1016:1040 The microbial communities in both wild and artificially cultivated soil samples 1016:1094 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 6 79 theme microbial 1020:1028 arg1 species-rich 1111:1122 species-rich 1111:1122 species-rich 1111:1122 The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. 36811005 3 80 theme atractylone 839:849 arg1 accumulation 806:817 the accumulation 802:817 the accumulation of polysaccharides, atractylone, and lactones 802:863 In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). 36118574 7 0 theme productivity 946:957 arg1 yield 920:924 a glucose yield 910:924 a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1 910:975 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 8 1 theme fermentation 1005:1016 arg1 mode 1018:1021 the established fermentation mode 989:1021 the established fermentation mode 989:1021 Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1. 36118574 7 2 theme 0.62 g g-1 929:938 arg1 yield 920:924 a glucose yield 910:924 a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1 910:975 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 3 3 theme chemical 327:334 arg1 industries 336:345 the food, pharmaceutical, and chemical industries 297:345 the food, pharmaceutical, and chemical industries 297:345 They are produced by a variety of microorganisms, and they are widely used in the food, pharmaceutical, and chemical industries. 36118574 0 4 from biosynthesis 10:21 arg1 glabrata 55:62 Candida glabrata 47:62 Candida glabrata 47:62 Efficient biosynthesis of exopolysaccharide in Candida glabrata by a fed-batch culture. 36118574 3 5 theme microorganisms 253:266 arg1 microorganisms 253:266 microorganisms 253:266 microorganisms 253:266 They are produced by a variety of microorganisms, and they are widely used in the food, pharmaceutical, and chemical industries. 36118574 3 5 theme microorganisms 253:266 arg1 variety 242:248 a variety 240:248 a variety of microorganisms 240:266 They are produced by a variety of microorganisms, and they are widely used in the food, pharmaceutical, and chemical industries. 36118574 6 6 theme shaking 661:667 arg1 flasks 669:674 shaking flasks 661:674 shaking flasks 661:674 By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. 36118574 8 7 theme 113.8 g L-1 1080:1090 arg1 yield 1071:1075 an exopolysaccharide yield 1050:1075 an exopolysaccharide yield of 113.8 g L-1 1050:1090 Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1. 36118574 7 8 theme aeration 765:772 arg1 rate 774:777 aeration rate 765:777 aeration rate 765:777 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 8 9 theme 15-L 1028:1031 arg1 fermenter 1033:1041 a 15-L fermenter 1026:1041 a 15-L fermenter 1026:1041 Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1. 36118574 2 10 theme microbial 160:168 arg1 exopolysaccharides 170:187 microbial exopolysaccharides 160:187 microbial exopolysaccharides 160:187 In particular, microbial exopolysaccharides have received much attention. 36118574 0 11 theme Efficient 0:8 arg1 biosynthesis 10:21 Efficient biosynthesis 0:21 Efficient biosynthesis of exopolysaccharide in Candida glabrata 0:62 Efficient biosynthesis of exopolysaccharide in Candida glabrata by a fed-batch culture. 36118574 3 12 used used 289:292 arg2 they 273:276 they 273:276 they 273:276 They are produced by a variety of microorganisms, and they are widely used in the food, pharmaceutical, and chemical industries. 36118574 6 13 theme design 638:643 arg1 optimization 645:656 orthogonal design optimization 627:656 orthogonal design optimization 627:656 By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. 36118574 4 14 contain has 389:391 arg2 capacity 397:404 the capacity to produce exopolysaccharide 393:433 the capacity to produce exopolysaccharide 393:433 The Candida glabrata mutant 4-C10, which has the capacity to produce exopolysaccharide, was previously obtained by random mutagenesis. 36118574 4 14 contain has 389:391 arg1 mutant 369:374 The Candida glabrata mutant 4-C10 348:380 The Candida glabrata mutant 4-C10 348:380 The Candida glabrata mutant 4-C10, which has the capacity to produce exopolysaccharide, was previously obtained by random mutagenesis. 36118574 8 15 theme glucose 1100:1106 arg1 yield 1108:1112 a glucose yield 1098:1112 a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1 1098:1163 Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1. 36118574 7 16 theme 1.24 g L-1 h-1 962:975 arg1 0.62 g g-1 929:938 0.62 g g-1 929:938 0.62 g g-1 929:938 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 7 16 theme 1.24 g L-1 h-1 962:975 arg1 productivity 946:957 a productivity 944:957 a productivity of 1.24 g L-1 h-1 944:975 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 0 17 theme exopolysaccharide 26:42 arg1 biosynthesis 10:21 Efficient biosynthesis 0:21 Efficient biosynthesis of exopolysaccharide in Candida glabrata 0:62 Efficient biosynthesis of exopolysaccharide in Candida glabrata by a fed-batch culture. 36118574 8 18 theme exopolysaccharide 1053:1069 arg1 yield 1071:1075 an exopolysaccharide yield 1050:1075 an exopolysaccharide yield of 113.8 g L-1 1050:1090 Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1. 36118574 8 19 theme 0.60 g g-1 1117:1126 arg1 yield 1108:1112 a glucose yield 1098:1112 a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1 1098:1163 Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1. 36118574 1 20 theme important 108:116 arg1 biomacromolecules 126:142 important natural biomacromolecules 108:142 important natural biomacromolecules 108:142 Polysaccharides are important natural biomacromolecules. 36118574 1 20 theme important 108:116 arg1 Polysaccharides 88:102 Polysaccharides 88:102 Polysaccharides 88:102 Polysaccharides are important natural biomacromolecules. 36118574 7 21 theme fermentation 886:897 arg1 mode 899:902 fermentation mode 886:902 fermentation mode 886:902 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 7 22 theme agitation 748:756 arg1 speed 758:762 agitation speed 748:762 agitation speed 748:762 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 1 23 theme natural 118:124 arg1 biomacromolecules 126:142 important natural biomacromolecules 108:142 important natural biomacromolecules 108:142 Polysaccharides are important natural biomacromolecules. 36118574 1 23 theme natural 118:124 arg1 Polysaccharides 88:102 Polysaccharides 88:102 Polysaccharides 88:102 Polysaccharides are important natural biomacromolecules. 36118574 7 24 theme constant 864:871 arg1 rate 873:876 a constant rate 862:876 a constant rate feeding fermentation mode 862:902 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 0 25 theme Candida 47:53 arg1 glabrata 55:62 Candida glabrata 47:62 Candida glabrata 47:62 Efficient biosynthesis of exopolysaccharide in Candida glabrata by a fed-batch culture. 36118574 7 26 theme glucose 912:918 arg1 yield 920:924 a glucose yield 910:924 a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1 910:975 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 6 27 theme factor 603:608 arg1 optimization 610:621 single factor optimization 596:621 single factor optimization 596:621 By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. 36118574 2 28 theme much 203:206 arg1 attention 208:216 much attention 203:216 much attention 203:216 In particular, microbial exopolysaccharides have received much attention. 36118574 6 29 theme orthogonal 627:636 arg1 optimization 645:656 orthogonal design optimization 627:656 orthogonal design optimization 627:656 By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. 36118574 4 30 theme Candida 352:358 arg1 mutant 369:374 The Candida glabrata mutant 4-C10 348:380 The Candida glabrata mutant 4-C10 348:380 The Candida glabrata mutant 4-C10, which has the capacity to produce exopolysaccharide, was previously obtained by random mutagenesis. 36118574 6 31 theme single 596:601 arg1 optimization 610:621 single factor optimization 596:621 single factor optimization 596:621 By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. 36118574 7 32 theme exopolysaccharide 828:844 arg1 118.6 g L-1 813:823 118.6 g L-1 813:823 118.6 g L-1 of exopolysaccharide 813:844 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 3 33 theme pharmaceutical 307:320 arg1 industries 336:345 the food, pharmaceutical, and chemical industries 297:345 the food, pharmaceutical, and chemical industries 297:345 They are produced by a variety of microorganisms, and they are widely used in the food, pharmaceutical, and chemical industries. 36118574 4 34 theme random 463:468 arg1 mutagenesis 470:480 random mutagenesis 463:480 random mutagenesis 463:480 The Candida glabrata mutant 4-C10, which has the capacity to produce exopolysaccharide, was previously obtained by random mutagenesis. 36118574 5 35 theme fermentation 566:577 arg1 optimization 579:590 systemic fermentation optimization 557:590 systemic fermentation optimization 557:590 In this study we aimed to further enhance exopolysaccharide production by systemic fermentation optimization. 36118574 8 36 theme productivity 1134:1145 arg1 yield 1108:1112 a glucose yield 1098:1112 a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1 1098:1163 Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1. 36118574 6 37 from optimization 645:656 arg1 flasks 669:674 shaking flasks 661:674 shaking flasks 661:674 By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. 36118574 6 38 theme medium 701:706 arg1 composition 708:718 an optimal fermentation medium composition 677:718 an optimal fermentation medium composition 677:718 By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. 36118574 3 39 theme food 301:304 arg1 industries 336:345 the food, pharmaceutical, and chemical industries 297:345 the food, pharmaceutical, and chemical industries 297:345 They are produced by a variety of microorganisms, and they are widely used in the food, pharmaceutical, and chemical industries. 36118574 4 40 theme glabrata 360:367 arg1 mutant 369:374 The Candida glabrata mutant 4-C10 348:380 The Candida glabrata mutant 4-C10 348:380 The Candida glabrata mutant 4-C10, which has the capacity to produce exopolysaccharide, was previously obtained by random mutagenesis. 36118574 6 41 theme fermentation 688:699 arg1 composition 708:718 an optimal fermentation medium composition 677:718 an optimal fermentation medium composition 677:718 By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. 36118574 7 42 theme fermentation 794:805 arg1 mode 807:810 fed-batch fermentation mode 784:810 fed-batch fermentation mode 784:810 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 36118574 8 43 theme 1.29 g L-1 h-1 1150:1163 arg1 0.60 g g-1 1117:1126 0.60 g g-1 1117:1126 0.60 g g-1 1117:1126 Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1. 36118574 8 43 theme 1.29 g L-1 h-1 1150:1163 arg1 productivity 1134:1145 a productivity 1132:1145 a productivity of 1.29 g L-1 h-1 1132:1163 Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1. 36118574 6 44 from optimization 610:621 arg1 flasks 669:674 shaking flasks 661:674 shaking flasks 661:674 By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. 36118574 5 45 theme systemic 557:564 arg1 optimization 579:590 systemic fermentation optimization 557:590 systemic fermentation optimization 557:590 In this study we aimed to further enhance exopolysaccharide production by systemic fermentation optimization. 36118574 8 46 theme established 993:1003 arg1 mode 1018:1021 the established fermentation mode 989:1021 the established fermentation mode 989:1021 Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1. 36118574 6 47 theme optimal 680:686 arg1 composition 708:718 an optimal fermentation medium composition 677:718 an optimal fermentation medium composition 677:718 By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. 36118574 0 48 theme fed-batch 69:77 arg1 culture 79:85 a fed-batch culture 67:85 a fed-batch culture 67:85 Efficient biosynthesis of exopolysaccharide in Candida glabrata by a fed-batch culture. 36118574 0 49 dep biosynthesis 10:21 arg1 culture 79:85 a fed-batch culture 67:85 a fed-batch culture 67:85 Efficient biosynthesis of exopolysaccharide in Candida glabrata by a fed-batch culture. 36118574 5 50 theme exopolysaccharide 525:541 arg1 production 543:552 exopolysaccharide production 525:552 exopolysaccharide production 525:552 In this study we aimed to further enhance exopolysaccharide production by systemic fermentation optimization. 36118574 7 51 theme fed-batch 784:792 arg1 fermentation 794:805 fed-batch fermentation 784:805 fed-batch fermentation mode 784:810 By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. 35962820 10 0 theme sulfur 1599:1604 arg1 source 1606:1611 a good sulfur source 1592:1611 a good sulfur source for cultivating sulfur-oxidizing bacteria 1592:1653 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 10 0 theme sulfur 1599:1604 arg1 biosulfur 1578:1586 biosulfur 1578:1586 biosulfur 1578:1586 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 3 1 theme globules 530:537 arg1 characteristics 501:515 the characteristics 497:515 the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 497:580 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 3 1 theme globules 530:537 arg1 possibility 590:600 the possibility 586:600 the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source 586:685 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 5 2 theme biosulfur 814:822 arg1 globule 824:830 The biosulfur globule 810:830 The biosulfur globule 810:830 The biosulfur globule was wrapped with an organic layer composed of polysaccharides and proteins. 35962820 0 3 theme Thioalkalivibrio 111:126 arg1 D301 137:140 haloalkaliphilic Thioalkalivibrio versutus D301 94:140 haloalkaliphilic Thioalkalivibrio versutus D301 94:140 Organic layer characteristics and microbial utilization of the biosulfur globules produced by haloalkaliphilic Thioalkalivibrio versutus D301 during biological desulfurization. 35962820 10 4 theme halophilus 1479:1488 arg1 rates 1370:1374 the growth rates 1359:1374 the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur 1359:1510 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 7 5 theme organic 1010:1016 arg1 layer 1018:1022 the organic layer 1006:1022 the organic layer 1006:1022 In the formation stage of biosulfur globules, the organic layer was dominated by polysaccharides, and in later stage, proteins became the main component. 35962820 0 6 theme haloalkaliphilic 94:109 arg1 D301 137:140 haloalkaliphilic Thioalkalivibrio versutus D301 94:140 haloalkaliphilic Thioalkalivibrio versutus D301 94:140 Organic layer characteristics and microbial utilization of the biosulfur globules produced by haloalkaliphilic Thioalkalivibrio versutus D301 during biological desulfurization. 35962820 7 7 theme globules 996:1003 arg1 stage 977:981 the formation stage 963:981 the formation stage of biosulfur globules 963:1003 In the formation stage of biosulfur globules, the organic layer was dominated by polysaccharides, and in later stage, proteins became the main component. 35962820 1 8 theme genus 198:202 arg1 Thioalkalivibrio 204:219 The haloalkaliphilic genus Thioalkalivibrio 177:219 The haloalkaliphilic genus Thioalkalivibrio 177:219 The haloalkaliphilic genus Thioalkalivibrio, widely used in bio-desulfurization, can oxidize H2S to So, which is excreted outside cells in the form of biosulfur globules. 35962820 8 9 theme organic 1198:1204 arg1 matter 1206:1211 organic matter 1198:1211 organic matter secreted by cells 1198:1229 We speculated that the organic layer was mainly formed by the passive adsorption of organic matter secreted by cells. 35962820 6 10 theme layer 940:944 arg1 composition 912:922 The composition 908:922 The composition of this organic layer 908:944 The composition of this organic layer could change. 35962820 3 11 theme versutus 568:575 arg1 D301 577:580 Thioalkalivibrio versutus D301 551:580 Thioalkalivibrio versutus D301 551:580 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 0 12 theme versutus 128:135 arg1 D301 137:140 haloalkaliphilic Thioalkalivibrio versutus D301 94:140 haloalkaliphilic Thioalkalivibrio versutus D301 94:140 Organic layer characteristics and microbial utilization of the biosulfur globules produced by haloalkaliphilic Thioalkalivibrio versutus D301 during biological desulfurization. 35962820 6 13 theme organic 932:938 arg1 layer 940:944 this organic layer 927:944 this organic layer 927:944 The composition of this organic layer could change. 35962820 2 14 from information 386:396 arg1 globules 411:418 biosulfur globules 401:418 biosulfur globules 401:418 As by-product of bio-desulfurization, information on biosulfur globules is still very scant, which limits its high-value utilization. 35962820 5 15 theme organic 852:858 arg1 layer 860:864 an organic layer 849:864 an organic layer composed of polysaccharides and proteins 849:905 The biosulfur globule was wrapped with an organic layer composed of polysaccharides and proteins. 35962820 10 16 theme sulfur-oxidizing 1629:1644 arg1 bacteria 1646:1653 cultivating sulfur-oxidizing bacteria 1617:1653 cultivating sulfur-oxidizing bacteria 1617:1653 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 0 17 theme layer 8:12 arg1 characteristics 14:28 Organic layer characteristics 0:28 Organic layer characteristics 0:28 Organic layer characteristics and microbial utilization of the biosulfur globules produced by haloalkaliphilic Thioalkalivibrio versutus D301 during biological desulfurization. 35962820 10 18 theme good 1594:1597 arg1 source 1606:1611 a good sulfur source 1592:1611 a good sulfur source for cultivating sulfur-oxidizing bacteria 1592:1653 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 10 18 theme good 1594:1597 arg1 biosulfur 1578:1586 biosulfur 1578:1586 biosulfur 1578:1586 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 7 19 theme biosulfur 986:994 arg1 globules 996:1003 biosulfur globules 986:1003 biosulfur globules 986:1003 In the formation stage of biosulfur globules, the organic layer was dominated by polysaccharides, and in later stage, proteins became the main component. 35962820 3 20 theme cultivating 605:615 arg1 bacteria 634:641 cultivating sulfur-oxidizing bacteria 605:641 cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source 605:685 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 4 21 from element 712:718 arg1 globules 737:744 the biosulfur globules 723:744 the biosulfur globules 723:744 The sulfur element in the biosulfur globules existed in the form α-S8, which was similar to chemical sulfur. 35962820 4 22 theme biosulfur 727:735 arg1 globules 737:744 the biosulfur globules 723:744 the biosulfur globules 723:744 The sulfur element in the biosulfur globules existed in the form α-S8, which was similar to chemical sulfur. 35962820 0 23 theme Organic 0:6 arg1 characteristics 14:28 Organic layer characteristics 0:28 Organic layer characteristics 0:28 Organic layer characteristics and microbial utilization of the biosulfur globules produced by haloalkaliphilic Thioalkalivibrio versutus D301 during biological desulfurization. 35962820 7 24 theme formation 967:975 arg1 stage 977:981 the formation stage 963:981 the formation stage of biosulfur globules 963:1003 In the formation stage of biosulfur globules, the organic layer was dominated by polysaccharides, and in later stage, proteins became the main component. 35962820 3 25 theme sulfur-oxidizing 617:632 arg1 bacteria 634:641 cultivating sulfur-oxidizing bacteria 605:641 cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source 605:685 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 9 26 with endowed 1263:1269 arg1 bioavailability 1293:1307 better bioavailability 1286:1307 better bioavailability 1286:1307 The existence of organic layer endowed biosulfur with better bioavailability. 35962820 2 27 theme high-value 458:467 arg1 utilization 469:479 its high-value utilization 454:479 its high-value utilization 454:479 As by-product of bio-desulfurization, information on biosulfur globules is still very scant, which limits its high-value utilization. 35962820 0 28 theme biological 149:158 arg1 desulfurization 160:174 biological desulfurization 149:174 biological desulfurization 149:174 Organic layer characteristics and microbial utilization of the biosulfur globules produced by haloalkaliphilic Thioalkalivibrio versutus D301 during biological desulfurization. 35962820 4 29 theme chemical 793:800 arg1 sulfur 802:807 chemical sulfur 793:807 chemical sulfur 793:807 The sulfur element in the biosulfur globules existed in the form α-S8, which was similar to chemical sulfur. 35962820 9 30 theme organic 1249:1255 arg1 layer 1257:1261 organic layer 1249:1261 organic layer 1249:1261 The existence of organic layer endowed biosulfur with better bioavailability. 35962820 10 31 theme chemical 1342:1349 arg1 sulfur 1351:1356 chemical sulfur 1342:1356 chemical sulfur 1342:1356 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 4 32 theme form 761:764 arg1 α-S8 766:769 the form α-S8 757:769 the form α-S8 757:769 The sulfur element in the biosulfur globules existed in the form α-S8, which was similar to chemical sulfur. 35962820 4 32 theme form 761:764 arg1 similar 782:788 similar 782:788 similar 782:788 The sulfur element in the biosulfur globules existed in the form α-S8, which was similar to chemical sulfur. 35962820 10 33 theme magnitude 1551:1559 arg1 order 1542:1546 an order 1539:1546 an order of magnitude 1539:1559 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 9 34 theme layer 1257:1261 arg1 existence 1236:1244 The existence 1232:1244 The existence of organic layer 1232:1261 The existence of organic layer endowed biosulfur with better bioavailability. 35962820 4 35 theme sulfur 705:710 arg1 element 712:718 The sulfur element 701:718 The sulfur element in the biosulfur globules 701:744 The sulfur element in the biosulfur globules existed in the form α-S8, which was similar to chemical sulfur. 35962820 0 36 theme microbial 34:42 arg1 utilization 44:54 microbial utilization 34:54 microbial utilization of the biosulfur globules 34:80 Organic layer characteristics and microbial utilization of the biosulfur globules produced by haloalkaliphilic Thioalkalivibrio versutus D301 during biological desulfurization. 35962820 3 37 theme high 648:651 arg1 source 680:685 a high biological-activity sulfur source 646:685 a high biological-activity sulfur source 646:685 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 10 38 theme cultivating 1617:1627 arg1 bacteria 1646:1653 cultivating sulfur-oxidizing bacteria 1617:1653 cultivating sulfur-oxidizing bacteria 1617:1653 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 10 39 dep several 1522:1528 arg1 folds 1530:1534 folds 1530:1534 folds 1530:1534 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 1 40 theme biosulfur 328:336 arg1 globules 338:345 biosulfur globules 328:345 biosulfur globules 328:345 The haloalkaliphilic genus Thioalkalivibrio, widely used in bio-desulfurization, can oxidize H2S to So, which is excreted outside cells in the form of biosulfur globules. 35962820 8 41 theme organic 1137:1143 arg1 layer 1145:1149 the organic layer 1133:1149 the organic layer 1133:1149 We speculated that the organic layer was mainly formed by the passive adsorption of organic matter secreted by cells. 35962820 3 42 theme bacteria 634:641 arg1 characteristics 501:515 the characteristics 497:515 the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 497:580 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 3 42 theme bacteria 634:641 arg1 possibility 590:600 the possibility 586:600 the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source 586:685 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 2 43 theme bio-desulfurization 365:383 arg1 by-product 351:360 by-product 351:360 by-product of bio-desulfurization 351:383 As by-product of bio-desulfurization, information on biosulfur globules is still very scant, which limits its high-value utilization. 35962820 1 44 theme globules 338:345 arg1 form 320:323 the form 316:323 the form of biosulfur globules 316:345 The haloalkaliphilic genus Thioalkalivibrio, widely used in bio-desulfurization, can oxidize H2S to So, which is excreted outside cells in the form of biosulfur globules. 35962820 7 45 theme main 1098:1101 arg1 component 1103:1111 the main component 1094:1111 the main component 1094:1111 In the formation stage of biosulfur globules, the organic layer was dominated by polysaccharides, and in later stage, proteins became the main component. 35962820 10 46 theme growth 1363:1368 arg1 rates 1370:1374 the growth rates 1359:1374 the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur 1359:1510 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 3 47 theme biosulfur 520:528 arg1 globules 530:537 biosulfur globules 520:537 biosulfur globules produced by Thioalkalivibrio versutus D301 520:580 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 7 48 theme later 1065:1069 arg1 stage 1071:1075 later stage 1065:1075 later stage 1065:1075 In the formation stage of biosulfur globules, the organic layer was dominated by polysaccharides, and in later stage, proteins became the main component. 35962820 9 49 theme better 1286:1291 arg1 bioavailability 1293:1307 better bioavailability 1286:1307 better bioavailability 1286:1307 The existence of organic layer endowed biosulfur with better bioavailability. 35962820 10 50 theme microaerophila 1437:1450 arg1 rates 1370:1374 the growth rates 1359:1374 the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur 1359:1510 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 8 51 theme matter 1206:1211 arg1 adsorption 1184:1193 the passive adsorption 1172:1193 the passive adsorption of organic matter secreted by cells 1172:1229 We speculated that the organic layer was mainly formed by the passive adsorption of organic matter secreted by cells. 35962820 1 52 theme haloalkaliphilic 181:196 arg1 Thioalkalivibrio 204:219 The haloalkaliphilic genus Thioalkalivibrio 177:219 The haloalkaliphilic genus Thioalkalivibrio 177:219 The haloalkaliphilic genus Thioalkalivibrio, widely used in bio-desulfurization, can oxidize H2S to So, which is excreted outside cells in the form of biosulfur globules. 35962820 0 53 theme globules 73:80 arg1 characteristics 14:28 Organic layer characteristics 0:28 Organic layer characteristics 0:28 Organic layer characteristics and microbial utilization of the biosulfur globules produced by haloalkaliphilic Thioalkalivibrio versutus D301 during biological desulfurization. 35962820 0 53 theme globules 73:80 arg1 utilization 44:54 microbial utilization 34:54 microbial utilization of the biosulfur globules 34:80 Organic layer characteristics and microbial utilization of the biosulfur globules produced by haloalkaliphilic Thioalkalivibrio versutus D301 during biological desulfurization. 35962820 3 54 theme biological-activity 653:671 arg1 source 680:685 a high biological-activity sulfur source 646:685 a high biological-activity sulfur source 646:685 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 10 55 theme ATCC 1409:1412 arg1 rates 1370:1374 the growth rates 1359:1374 the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur 1359:1510 Compared with those found using chemical sulfur, the growth rates of Acidithiobacillus thiooxidans ATCC 19377T, Thiomicrospira microaerophila BDL05 and Thioalkalibacter halophilus BDH06 using biosulfur increased several folds to an order of magnitude, indicating that biosulfur was a good sulfur source for cultivating sulfur-oxidizing bacteria. 35962820 2 56 theme biosulfur 401:409 arg1 globules 411:418 biosulfur globules 401:418 biosulfur globules 401:418 As by-product of bio-desulfurization, information on biosulfur globules is still very scant, which limits its high-value utilization. 35962820 0 57 theme biosulfur 63:71 arg1 globules 73:80 the biosulfur globules 59:80 the biosulfur globules 59:80 Organic layer characteristics and microbial utilization of the biosulfur globules produced by haloalkaliphilic Thioalkalivibrio versutus D301 during biological desulfurization. 35962820 3 58 theme sulfur 673:678 arg1 source 680:685 a high biological-activity sulfur source 646:685 a high biological-activity sulfur source 646:685 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 3 59 theme Thioalkalivibrio 551:566 arg1 D301 577:580 Thioalkalivibrio versutus D301 551:580 Thioalkalivibrio versutus D301 551:580 In this paper, the characteristics of biosulfur globules produced by Thioalkalivibrio versutus D301 and the possibility of cultivating sulfur-oxidizing bacteria as a high biological-activity sulfur source were studied. 35962820 8 60 theme passive 1176:1182 arg1 adsorption 1184:1193 the passive adsorption 1172:1193 the passive adsorption of organic matter secreted by cells 1172:1229 We speculated that the organic layer was mainly formed by the passive adsorption of organic matter secreted by cells. 36766120 2 0 theme conventional 445:456 arg1 HW 480:481 HW 480:481 HW 480:481 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 2 0 theme conventional 445:456 arg1 extraction 468:477 conventional hot water extraction 445:477 conventional hot water extraction (HW) 445:482 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 9 1 theme extraction 1447:1456 arg1 strategy 1484:1491 a promising strategy 1472:1491 a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods 1472:1583 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 9 1 theme extraction 1447:1456 arg1 method 1458:1463 the ultrasound-assisted DES extraction method 1419:1463 the ultrasound-assisted DES extraction method 1419:1463 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 7 2 dep transform 1276:1284 arg1 infrared 1286:1293 infrared 1286:1293 transform infrared analysis 1276:1302 Little difference was observed in the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis. 36766120 6 3 theme CHP 1061:1063 arg1 structure 1048:1056 the molecular structure 1034:1056 the molecular structure of CHP 1034:1063 Monosaccharide composition analysis displayed that the molecular structure of CHP exhibited more arabinose but less glucose, mannose, galacturonic acid, and glucuronic acid than HWP. 36766120 4 4 dep in 803:804 arg1 vitro 806:810 vitro 806:810 vitro 806:810 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 2 5 from tea 416:418 arg1 TPs 395:397 TPs 395:397 TPs 395:397 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 2 5 from tea 416:418 arg1 polysaccharides 378:392 extract tea polysaccharides 366:392 extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW) 366:482 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 9 6 theme excellent 1517:1525 arg1 bioactivities 1527:1539 excellent bioactivities 1517:1539 excellent bioactivities for future applications in functional foods 1517:1583 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 5 7 theme molecular 965:973 arg1 weight 975:980 a lower molecular weight 957:980 a lower molecular weight 957:980 Furthermore, compared to the HWP, the CHP had a higher extraction yield and total carbohydrate content and a lower molecular weight. 36766120 9 8 theme DES 1443:1445 arg1 strategy 1484:1491 a promising strategy 1472:1491 a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods 1472:1583 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 9 8 theme DES 1443:1445 arg1 method 1458:1463 the ultrasound-assisted DES extraction method 1419:1463 the ultrasound-assisted DES extraction method 1419:1463 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 9 9 theme functional 1568:1577 arg1 foods 1579:1583 functional foods 1568:1583 functional foods 1568:1583 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 6 10 theme galacturonic 1117:1128 arg1 acid 1130:1133 galacturonic acid 1117:1133 galacturonic acid 1117:1133 Monosaccharide composition analysis displayed that the molecular structure of CHP exhibited more arabinose but less glucose, mannose, galacturonic acid, and glucuronic acid than HWP. 36766120 3 11 theme physicochemical 489:503 arg1 properties 533:542 The physicochemical, structural, and biological properties 485:542 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) 485:606 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) were further investigated. 36766120 8 12 theme α-glucosidase 1335:1347 arg1 activity 1377:1384 α-glucosidase inhibitory and hypoglycemic activity 1335:1384 α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP 1335:1405 Besides, CHP possessed better α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP. 36766120 1 13 theme recent 257:262 arg1 years 264:268 recent years 257:268 recent years 257:268 Deep eutectic solvent as a new green and safe solvent system has attracted more and more attention in recent years. 36766120 4 14 theme choline 682:688 arg1 chloride 690:697 choline chloride 682:697 choline chloride 682:697 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 9 15 theme promising 1474:1482 arg1 strategy 1484:1491 a promising strategy 1472:1491 a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods 1472:1583 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 9 15 theme promising 1474:1482 arg1 method 1458:1463 the ultrasound-assisted DES extraction method 1419:1463 the ultrasound-assisted DES extraction method 1419:1463 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 9 16 from applications 1552:1563 arg1 foods 1579:1583 functional foods 1568:1583 functional foods 1568:1583 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 6 17 dep glucose 1099:1105 arg1 less 1094:1097 less 1094:1097 less 1094:1097 Monosaccharide composition analysis displayed that the molecular structure of CHP exhibited more arabinose but less glucose, mannose, galacturonic acid, and glucuronic acid than HWP. 36766120 4 18 theme extraction 773:782 arg1 yield 784:788 the optimal extraction yield 761:788 the optimal extraction yield (19.18%) 761:797 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 4 18 theme extraction 773:782 arg1 % 796:796 19.18% 791:796 19.18% 791:796 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 2 19 theme tea 374:376 arg1 TPs 395:397 TPs 395:397 TPs 395:397 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 2 19 theme tea 374:376 arg1 polysaccharides 378:392 extract tea polysaccharides 366:392 extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW) 366:482 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 4 20 theme optimal 765:771 arg1 yield 784:788 the optimal extraction yield 761:788 the optimal extraction yield (19.18%) 761:797 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 4 20 theme optimal 765:771 arg1 % 796:796 19.18% 791:796 19.18% 791:796 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 2 21 theme white 410:414 arg1 tea 416:418 Anji white tea 405:418 Anji white tea 405:418 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 8 22 theme L6 1389:1390 arg1 cells 1392:1396 L6 cells 1389:1396 L6 cells 1389:1396 Besides, CHP possessed better α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP. 36766120 1 23 theme new 182:184 arg1 system 209:214 a new green and safe solvent system 180:214 a new green and safe solvent system 180:214 Deep eutectic solvent as a new green and safe solvent system has attracted more and more attention in recent years. 36766120 0 24 theme Deep 20:23 arg1 Extraction 42:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction 0:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 0:153 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 0 25 from Extraction 42:51 arg1 Tea 88:90 Anji White Tea 77:90 Anji White Tea 77:90 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 6 26 theme glucuronic 1140:1149 arg1 acid 1151:1154 glucuronic acid 1140:1154 glucuronic acid 1140:1154 Monosaccharide composition analysis displayed that the molecular structure of CHP exhibited more arabinose but less glucose, mannose, galacturonic acid, and glucuronic acid than HWP. 36766120 0 27 with Comparison 114:123 arg1 Method 147:152 the Conventional Method 130:152 the Conventional Method 130:152 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 2 28 theme eutectic 297:304 arg1 DES 316:318 DES 316:318 DES 316:318 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 2 28 theme eutectic 297:304 arg1 solvents 306:313 three deep eutectic solvents 286:313 three deep eutectic solvents (DES) 286:319 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 4 29 theme in 803:804 arg1 activities 824:833 in vitro antioxidant activities 803:833 in vitro antioxidant activities for TPs (CHP) 803:847 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 7 30 theme preliminary 1204:1214 arg1 characteristics 1227:1241 the preliminary structural characteristics 1200:1241 the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis 1200:1302 Little difference was observed in the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis. 36766120 0 31 theme Ultrasound-Assisted 0:18 arg1 Extraction 42:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction 0:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 0:153 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 2 32 theme deep 292:295 arg1 DES 316:318 DES 316:318 DES 316:318 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 2 32 theme deep 292:295 arg1 solvents 306:313 three deep eutectic solvents 286:313 three deep eutectic solvents (DES) 286:319 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 7 33 from Fourier 1268:1274 arg1 CHP 1259:1261 CHP 1259:1261 CHP 1259:1261 Little difference was observed in the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis. 36766120 7 33 from Fourier 1268:1274 arg1 HWP 1251:1253 HWP 1251:1253 HWP 1251:1253 Little difference was observed in the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis. 36766120 7 34 theme structural 1216:1225 arg1 characteristics 1227:1241 the preliminary structural characteristics 1200:1241 the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis 1200:1302 Little difference was observed in the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis. 36766120 0 35 theme Solvent 34:40 arg1 Extraction 42:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction 0:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 0:153 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 0 36 theme Conventional 134:145 arg1 Method 147:152 the Conventional Method 130:152 the Conventional Method 130:152 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 0 37 with Characterization 93:108 arg1 Method 147:152 the Conventional Method 130:152 the Conventional Method 130:152 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 3 38 theme structural 506:515 arg1 properties 533:542 The physicochemical, structural, and biological properties 485:542 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) 485:606 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) were further investigated. 36766120 4 39 theme 1:2 747:749 arg1 ratio 738:742 the molar ratio 728:742 the molar ratio of 1:2 728:749 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 1 40 theme safe 196:199 arg1 system 209:214 a new green and safe solvent system 180:214 a new green and safe solvent system 180:214 Deep eutectic solvent as a new green and safe solvent system has attracted more and more attention in recent years. 36766120 0 41 theme Eutectic 25:32 arg1 Extraction 42:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction 0:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 0:153 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 8 42 theme hypoglycemic 1364:1375 arg1 activity 1377:1384 α-glucosidase inhibitory and hypoglycemic activity 1335:1384 α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP 1335:1405 Besides, CHP possessed better α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP. 36766120 6 43 theme molecular 1038:1046 arg1 structure 1048:1056 the molecular structure 1034:1056 the molecular structure of CHP 1034:1063 Monosaccharide composition analysis displayed that the molecular structure of CHP exhibited more arabinose but less glucose, mannose, galacturonic acid, and glucuronic acid than HWP. 36766120 1 44 theme solvent 201:207 arg1 system 209:214 a new green and safe solvent system 180:214 a new green and safe solvent system 180:214 Deep eutectic solvent as a new green and safe solvent system has attracted more and more attention in recent years. 36766120 0 45 from Tea 88:90 arg1 Polysaccharides 56:70 Polysaccharides 56:70 Polysaccharides from Anji White Tea 56:90 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 0 45 from Tea 88:90 arg1 Extraction 42:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction 0:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 0:153 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 3 46 theme TPs 547:549 arg1 properties 533:542 The physicochemical, structural, and biological properties 485:542 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) 485:606 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) were further investigated. 36766120 3 47 theme biological 522:531 arg1 properties 533:542 The physicochemical, structural, and biological properties 485:542 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) 485:606 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) were further investigated. 36766120 7 48 dep Fourier 1268:1274 arg1 transform 1276:1284 transform 1276:1284 transform infrared analysis 1276:1302 Little difference was observed in the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis. 36766120 3 49 theme hot 592:594 arg1 HWP 603:605 HWP 603:605 HWP 603:605 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) were further investigated. 36766120 3 49 theme hot 592:594 arg1 water 596:600 hot water 592:600 hot water (HWP) 592:606 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) were further investigated. 36766120 2 50 theme Anji 405:408 arg1 tea 416:418 Anji white tea 405:418 Anji white tea 405:418 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 8 51 from activity 1377:1384 arg1 cells 1392:1396 L6 cells 1389:1396 L6 cells 1389:1396 Besides, CHP possessed better α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP. 36766120 2 52 theme water 462:466 arg1 HW 480:481 HW 480:481 HW 480:481 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 2 52 theme water 462:466 arg1 extraction 468:477 conventional hot water extraction 445:477 conventional hot water extraction (HW) 445:482 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 5 53 theme total 926:930 arg1 content 945:951 total carbohydrate content 926:951 total carbohydrate content 926:951 Furthermore, compared to the HWP, the CHP had a higher extraction yield and total carbohydrate content and a lower molecular weight. 36766120 5 54 theme extraction 905:914 arg1 yield 916:920 a higher extraction yield 896:920 a higher extraction yield 896:920 Furthermore, compared to the HWP, the CHP had a higher extraction yield and total carbohydrate content and a lower molecular weight. 36766120 6 55 theme composition 998:1008 arg1 analysis 1010:1017 Monosaccharide composition analysis 983:1017 Monosaccharide composition analysis 983:1017 Monosaccharide composition analysis displayed that the molecular structure of CHP exhibited more arabinose but less glucose, mannose, galacturonic acid, and glucuronic acid than HWP. 36766120 4 56 theme DES 659:661 arg1 system 663:668 the DES system 655:668 the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 655:749 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 0 57 theme Polysaccharides 56:70 arg1 Extraction 42:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction 0:51 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 0:153 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 4 58 theme TPs 839:841 arg1 CHP 844:846 TPs (CHP) 839:847 TPs (CHP) 839:847 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 1 59 dep new 182:184 arg1 green 186:190 green 186:190 green 186:190 Deep eutectic solvent as a new green and safe solvent system has attracted more and more attention in recent years. 36766120 7 60 theme Little 1166:1171 arg1 difference 1173:1182 Little difference 1166:1182 Little difference 1166:1182 Little difference was observed in the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis. 36766120 5 61 theme lower 959:963 arg1 weight 975:980 a lower molecular weight 957:980 a lower molecular weight 957:980 Furthermore, compared to the HWP, the CHP had a higher extraction yield and total carbohydrate content and a lower molecular weight. 36766120 4 62 theme molar 732:736 arg1 ratio 738:742 the molar ratio 728:742 the molar ratio of 1:2 728:749 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 1 63 theme Deep 155:158 arg1 solvent 169:175 Deep eutectic solvent 155:175 Deep eutectic solvent as a new green and safe solvent system 155:214 Deep eutectic solvent as a new green and safe solvent system has attracted more and more attention in recent years. 36766120 9 64 theme future 1545:1550 arg1 applications 1552:1563 future applications 1545:1563 future applications in functional foods 1545:1583 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 5 65 theme higher 898:903 arg1 yield 916:920 a higher extraction yield 896:920 a higher extraction yield 896:920 Furthermore, compared to the HWP, the CHP had a higher extraction yield and total carbohydrate content and a lower molecular weight. 36766120 8 66 contain possessed 1318:1326 arg1 CHP 1314:1316 CHP 1314:1316 CHP 1314:1316 Besides, CHP possessed better α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP. 36766120 8 66 contain possessed 1318:1326 arg2 activity 1377:1384 α-glucosidase inhibitory and hypoglycemic activity 1335:1384 α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP 1335:1405 Besides, CHP possessed better α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP. 36766120 9 67 with TPs 1508:1510 arg1 bioactivities 1527:1539 excellent bioactivities 1517:1539 excellent bioactivities for future applications in functional foods 1517:1583 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 4 68 theme antioxidant 812:822 arg1 activities 824:833 in vitro antioxidant activities 803:833 in vitro antioxidant activities for TPs (CHP) 803:847 Results showed that the DES system composed of choline chloride and 1,6-hexanediol (CH) with the molar ratio of 1:2 exhibited the optimal extraction yield (19.18%) and in vitro antioxidant activities for TPs (CHP). 36766120 5 69 theme carbohydrate 932:943 arg1 content 945:951 total carbohydrate content 926:951 total carbohydrate content 926:951 Furthermore, compared to the HWP, the CHP had a higher extraction yield and total carbohydrate content and a lower molecular weight. 36766120 0 70 dep Extraction 42:51 arg1 Comparison 114:123 Comparison 114:123 Comparison with the Conventional Method 114:152 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 0 70 dep Extraction 42:51 arg1 Characterization 93:108 Characterization 93:108 Characterization 93:108 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 6 71 theme Monosaccharide 983:996 arg1 analysis 1010:1017 Monosaccharide composition analysis 983:1017 Monosaccharide composition analysis 983:1017 Monosaccharide composition analysis displayed that the molecular structure of CHP exhibited more arabinose but less glucose, mannose, galacturonic acid, and glucuronic acid than HWP. 36766120 1 72 theme more 230:233 arg1 attention 244:252 more and more attention 230:252 more and more attention 230:252 Deep eutectic solvent as a new green and safe solvent system has attracted more and more attention in recent years. 36766120 0 73 theme White 82:86 arg1 Tea 88:90 Anji White Tea 77:90 Anji White Tea 77:90 Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides from Anji White Tea: Characterization and Comparison with the Conventional Method. 36766120 8 74 theme inhibitory 1349:1358 arg1 activity 1377:1384 α-glucosidase inhibitory and hypoglycemic activity 1335:1384 α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP 1335:1405 Besides, CHP possessed better α-glucosidase inhibitory and hypoglycemic activity in L6 cells than HWP. 36766120 9 75 theme ultrasound-assisted 1423:1441 arg1 strategy 1484:1491 a promising strategy 1472:1491 a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods 1472:1583 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 9 75 theme ultrasound-assisted 1423:1441 arg1 method 1458:1463 the ultrasound-assisted DES extraction method 1419:1463 the ultrasound-assisted DES extraction method 1419:1463 Therefore, the ultrasound-assisted DES extraction method can be a promising strategy for extracting TPs with excellent bioactivities for future applications in functional foods. 36766120 2 76 theme ultrasound 340:349 arg1 irradiation 351:361 ultrasound irradiation 340:361 ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW) 340:482 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 2 77 theme extract 366:372 arg1 TPs 395:397 TPs 395:397 TPs 395:397 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 2 77 theme extract 366:372 arg1 polysaccharides 378:392 extract tea polysaccharides 366:392 extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW) 366:482 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 2 78 theme hot 458:460 arg1 HW 480:481 HW 480:481 HW 480:481 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 2 78 theme hot 458:460 arg1 extraction 468:477 conventional hot water extraction 445:477 conventional hot water extraction (HW) 445:482 In this study, three deep eutectic solvents (DES) were combined with ultrasound irradiation to extract tea polysaccharides (TPs) from Anji white tea, which was compared with conventional hot water extraction (HW). 36766120 3 79 theme ultrasound-assisted 564:582 arg1 DES 584:586 ultrasound-assisted DES 564:586 ultrasound-assisted DES 564:586 The physicochemical, structural, and biological properties of TPs extracted by ultrasound-assisted DES and hot water (HWP) were further investigated. 36766120 7 80 located observed 1188:1195 arg2 difference 1173:1182 Little difference 1166:1182 Little difference 1166:1182 Little difference was observed in the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis. 36766120 7 80 located observed 1188:1195 arg1 characteristics 1227:1241 the preliminary structural characteristics 1200:1241 the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis 1200:1302 Little difference was observed in the preliminary structural characteristics between HWP and CHP from Fourier transform infrared analysis. 36766120 1 81 theme eutectic 160:167 arg1 solvent 169:175 Deep eutectic solvent 155:175 Deep eutectic solvent as a new green and safe solvent system 155:214 Deep eutectic solvent as a new green and safe solvent system has attracted more and more attention in recent years. 36766120 5 82 contain had 892:894 arg1 CHP 888:890 the CHP 884:890 the CHP 884:890 Furthermore, compared to the HWP, the CHP had a higher extraction yield and total carbohydrate content and a lower molecular weight. 36766120 5 82 contain had 892:894 arg2 yield 916:920 a higher extraction yield 896:920 a higher extraction yield 896:920 Furthermore, compared to the HWP, the CHP had a higher extraction yield and total carbohydrate content and a lower molecular weight. 36766120 5 82 contain had 892:894 arg2 content 945:951 total carbohydrate content 926:951 total carbohydrate content 926:951 Furthermore, compared to the HWP, the CHP had a higher extraction yield and total carbohydrate content and a lower molecular weight. 36766120 1 83 theme more 239:242 arg1 attention 244:252 more and more attention 230:252 more and more attention 230:252 Deep eutectic solvent as a new green and safe solvent system has attracted more and more attention in recent years. 35377640 6 0 theme reaction 1039:1046 arg1 mixtures 1048:1055 the crude reaction mixtures 1029:1055 the crude reaction mixtures 1029:1055 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 4 1 gly glycosylation 605:617 arg1 strategy 632:639 a one-pot strategy 622:639 a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5 622:708 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 35377640 1 2 theme cellular 178:185 arg1 glycoproteins 187:199 several cellular glycoproteins 170:199 several cellular glycoproteins 170:199 N-Glycans are major constituents of several cellular glycoproteins. 35377640 4 3 theme direct 571:576 arg1 β-mannosylation 578:592 triflate-mediated direct β-mannosylation 553:592 triflate-mediated direct β-mannosylation 553:592 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 35377640 6 4 theme spectrometry-based 922:939 arg1 analysis 954:961 ion mobility-mass spectrometry-based quantitative analysis 904:961 ion mobility-mass spectrometry-based quantitative analysis 904:961 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 1 5 theme glycoproteins 187:199 arg1 N-Glycans 134:142 N-Glycans 134:142 N-Glycans 134:142 N-Glycans are major constituents of several cellular glycoproteins. 35377640 1 5 theme glycoproteins 187:199 arg1 constituents 154:165 major constituents 148:165 major constituents of several cellular glycoproteins 148:199 N-Glycans are major constituents of several cellular glycoproteins. 35377640 0 6 theme N-Linked 107:114 arg1 Oligosaccharides 116:131 N-Linked Oligosaccharides 107:131 N-Linked Oligosaccharides 107:131 One-Pot Glycosylation Strategy Assisted by Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides. 35377640 4 7 theme triflate-mediated 553:569 arg1 β-mannosylation 578:592 triflate-mediated direct β-mannosylation 553:592 triflate-mediated direct β-mannosylation 553:592 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 35377640 5 8 theme one-pot 726:732 arg1 glycosylation 745:757 a one-pot sequential glycosylation 724:757 a one-pot sequential glycosylation of the N-linked trisaccharide core 7 724:794 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 3 9 theme N-glycans 413:421 arg1 synthesis 400:408 the synthesis 396:408 the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions 396:527 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 5 10 theme high-mannose 814:825 arg1 N-glycans 832:840 diverse high-mannose type N-glycans 806:840 diverse high-mannose type N-glycans 806:840 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 5 11 theme sequential 734:743 arg1 glycosylation 745:757 a one-pot sequential glycosylation 724:757 a one-pot sequential glycosylation of the N-linked trisaccharide core 7 724:794 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 6 12 theme ion 904:906 arg1 analysis 954:961 ion mobility-mass spectrometry-based quantitative analysis 904:961 ion mobility-mass spectrometry-based quantitative analysis 904:961 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 3 13 theme double 368:373 arg1 strategy 383:390 a double one-pot strategy 366:390 a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions 366:527 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 4 14 theme core 701:704 arg1 synthesis 649:657 the synthesis 645:657 the synthesis of the challenging N-linked trisaccharide core β-5 645:708 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 35377640 4 15 gly includes 544:551 arg1 strategy 632:639 a one-pot strategy 622:639 a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5 622:708 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 35377640 0 16 theme Oligosaccharides 116:131 arg1 Synthesis 94:102 the Synthesis 90:102 the Synthesis of N-Linked Oligosaccharides 90:131 One-Pot Glycosylation Strategy Assisted by Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides. 35377640 6 17 theme regioselective 1002:1015 arg1 outcomes 1017:1024 the stereo- and regioselective outcomes 986:1024 the stereo- and regioselective outcomes of the crude reaction mixtures 986:1055 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 2 18 theme samples 297:303 arg1 generation 278:287 the rapid generation 268:287 the rapid generation of pure samples to determine their biological functions 268:343 One-pot strategies for the synthesis of N-glycans are crucial for the rapid generation of pure samples to determine their biological functions. 35377640 3 19 theme rapid 466:470 arg1 screening 472:480 rapid screening 466:480 rapid screening of optimized glycosylation reaction conditions 466:527 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 0 20 theme Glycosylation 8:20 arg1 Strategy 22:29 One-Pot Glycosylation Strategy 0:29 One-Pot Glycosylation Strategy 0:29 One-Pot Glycosylation Strategy Assisted by Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides. 35377640 6 21 theme efficient 1077:1085 arg1 protocol 1095:1102 a highly efficient one-pot protocol 1068:1102 a highly efficient one-pot protocol 1068:1102 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 6 22 theme crude 1033:1037 arg1 mixtures 1048:1055 the crude reaction mixtures 1029:1055 the crude reaction mixtures 1029:1055 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 3 23 theme analysis 444:451 arg1 approach 453:460 an IM-MS analysis approach 435:460 an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions 435:527 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 0 24 theme One-Pot 0:6 arg1 Strategy 22:29 One-Pot Glycosylation Strategy 0:29 One-Pot Glycosylation Strategy 0:29 One-Pot Glycosylation Strategy Assisted by Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides. 35377640 6 25 theme quantitative 941:952 arg1 analysis 954:961 ion mobility-mass spectrometry-based quantitative analysis 904:961 ion mobility-mass spectrometry-based quantitative analysis 904:961 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 5 26 theme trisaccharide 775:787 arg1 core 789:792 the N-linked trisaccharide core 7 762:794 the N-linked trisaccharide core 7 762:794 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 3 27 theme optimized 485:493 arg1 conditions 518:527 optimized glycosylation reaction conditions 485:527 optimized glycosylation reaction conditions 485:527 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 6 28 theme one-pot 1087:1093 arg1 protocol 1095:1102 a highly efficient one-pot protocol 1068:1102 a highly efficient one-pot protocol 1068:1102 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 5 29 theme core 789:792 arg1 glycosylation 745:757 a one-pot sequential glycosylation 724:757 a one-pot sequential glycosylation of the N-linked trisaccharide core 7 724:794 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 6 30 theme stereo- 990:996 arg1 outcomes 1017:1024 the stereo- and regioselective outcomes 986:1024 the stereo- and regioselective outcomes of the crude reaction mixtures 986:1055 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 2 31 theme biological 324:333 arg1 functions 335:343 their biological functions 318:343 their biological functions 318:343 One-pot strategies for the synthesis of N-glycans are crucial for the rapid generation of pure samples to determine their biological functions. 35377640 3 32 theme glycosylation 495:507 arg1 conditions 518:527 optimized glycosylation reaction conditions 485:527 optimized glycosylation reaction conditions 485:527 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 0 33 theme Ion 43:45 arg1 Analysis 74:81 Ion Mobility-Mass Spectrometry Analysis 43:81 Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides 43:131 One-Pot Glycosylation Strategy Assisted by Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides. 35377640 4 34 theme one-pot 624:630 arg1 strategy 632:639 a one-pot strategy 622:639 a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5 622:708 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 35377640 4 35 link N-linked 678:685 arg1 core 701:704 the challenging N-linked trisaccharide core β-5 662:708 the challenging N-linked trisaccharide core β-5 662:708 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 35377640 3 36 theme IM-MS 438:442 arg1 approach 453:460 an IM-MS analysis approach 435:460 an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions 435:527 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 2 37 theme One-pot 202:208 arg1 strategies 210:219 One-pot strategies 202:219 One-pot strategies for the synthesis of N-glycans 202:250 One-pot strategies for the synthesis of N-glycans are crucial for the rapid generation of pure samples to determine their biological functions. 35377640 3 38 theme one-pot 375:381 arg1 strategy 383:390 a double one-pot strategy 366:390 a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions 366:527 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 0 39 theme Spectrometry 61:72 arg1 Analysis 74:81 Ion Mobility-Mass Spectrometry Analysis 43:81 Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides 43:131 One-Pot Glycosylation Strategy Assisted by Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides. 35377640 5 40 theme diverse 806:812 arg1 N-glycans 832:840 diverse high-mannose type N-glycans 806:840 diverse high-mannose type N-glycans 806:840 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 5 41 theme excellent 847:855 arg1 stereo- 857:863 excellent stereo- 847:863 excellent stereo- 847:863 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 0 42 theme Mobility-Mass 47:59 arg1 Analysis 74:81 Ion Mobility-Mass Spectrometry Analysis 43:81 Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides 43:131 One-Pot Glycosylation Strategy Assisted by Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides. 35377640 2 43 theme N-glycans 242:250 arg1 synthesis 229:237 the synthesis 225:237 the synthesis of N-glycans 225:250 One-pot strategies for the synthesis of N-glycans are crucial for the rapid generation of pure samples to determine their biological functions. 35377640 5 44 link N-linked 766:773 arg1 core 789:792 the N-linked trisaccharide core 7 762:794 the N-linked trisaccharide core 7 762:794 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 4 45 theme tandem 598:603 arg1 glycosylation 605:617 tandem glycosylation 598:617 tandem glycosylation 598:617 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 35377640 1 46 gly glycoproteins 187:199 arg1 glycoproteins 187:199 several cellular glycoproteins 170:199 several cellular glycoproteins 170:199 N-Glycans are major constituents of several cellular glycoproteins. 35377640 2 47 theme pure 292:295 arg1 samples 297:303 pure samples 292:303 pure samples 292:303 One-pot strategies for the synthesis of N-glycans are crucial for the rapid generation of pure samples to determine their biological functions. 35377640 6 48 theme mobility-mass 908:920 arg1 analysis 954:961 ion mobility-mass spectrometry-based quantitative analysis 904:961 ion mobility-mass spectrometry-based quantitative analysis 904:961 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 1 49 theme major 148:152 arg1 N-Glycans 134:142 N-Glycans 134:142 N-Glycans 134:142 N-Glycans are major constituents of several cellular glycoproteins. 35377640 1 49 theme major 148:152 arg1 constituents 154:165 major constituents 148:165 major constituents of several cellular glycoproteins 148:199 N-Glycans are major constituents of several cellular glycoproteins. 35377640 4 50 theme challenging 666:676 arg1 core 701:704 the challenging N-linked trisaccharide core β-5 662:708 the challenging N-linked trisaccharide core β-5 662:708 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 35377640 5 51 theme N-linked 766:773 arg1 core 789:792 the N-linked trisaccharide core 7 762:794 the N-linked trisaccharide core 7 762:794 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 3 52 theme conditions 518:527 arg1 screening 472:480 rapid screening 466:480 rapid screening of optimized glycosylation reaction conditions 466:527 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 3 53 theme reaction 509:516 arg1 conditions 518:527 optimized glycosylation reaction conditions 485:527 optimized glycosylation reaction conditions 485:527 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 5 54 theme type 827:830 arg1 N-glycans 832:840 diverse high-mannose type N-glycans 806:840 diverse high-mannose type N-glycans 806:840 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 5 55 gly glycosylation 745:757 arg1 core 789:792 the N-linked trisaccharide core 7 762:794 the N-linked trisaccharide core 7 762:794 Furthermore, a one-pot sequential glycosylation of the N-linked trisaccharide core 7 furnishes diverse high-mannose type N-glycans with excellent stereo- and regioselectivities. 35377640 4 56 theme trisaccharide 687:699 arg1 core 701:704 the challenging N-linked trisaccharide core β-5 662:708 the challenging N-linked trisaccharide core β-5 662:708 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 35377640 3 57 theme assisted 423:430 arg1 N-glycans 413:421 N-glycans assisted 413:430 N-glycans assisted 413:430 Herein, we describe a double one-pot strategy for the synthesis of N-glycans assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. 35377640 6 58 theme mixtures 1048:1055 arg1 outcomes 1017:1024 the stereo- and regioselective outcomes 986:1024 the stereo- and regioselective outcomes of the crude reaction mixtures 986:1055 In particular, ion mobility-mass spectrometry-based quantitative analysis is applied to identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol. 35377640 2 59 theme rapid 272:276 arg1 generation 278:287 the rapid generation 268:287 the rapid generation of pure samples to determine their biological functions 268:343 One-pot strategies for the synthesis of N-glycans are crucial for the rapid generation of pure samples to determine their biological functions. 35377640 1 60 theme several 170:176 arg1 glycoproteins 187:199 several cellular glycoproteins 170:199 several cellular glycoproteins 170:199 N-Glycans are major constituents of several cellular glycoproteins. 35377640 4 61 theme N-linked 678:685 arg1 core 701:704 the challenging N-linked trisaccharide core β-5 662:708 the challenging N-linked trisaccharide core β-5 662:708 This research includes triflate-mediated direct β-mannosylation and tandem glycosylation in a one-pot strategy for the synthesis of the challenging N-linked trisaccharide core β-5. 36972171 0 0 theme sequence 109:116 arg1 retrotranslocation 74:91 luminal-to-cytosolic retrotranslocation 53:91 luminal-to-cytosolic retrotranslocation of glycosylated sequence 53:116 Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence. 36972171 0 1 theme glycosylated 96:107 arg1 sequence 109:116 glycosylated sequence 96:116 glycosylated sequence 96:116 Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence. 36972171 4 2 gly glycosylated 646:657 arg1 N163 659:662 N163 659:662 glycosylated N163 but not N132 646:675 In the absence of ceramide, the sequence surrounding glycosylated N163 but not N132 is retrotranslocated from lumen to cytosol independent of ER-associated degradation. 36972171 7 3 theme topological 1159:1169 arg1 regulation 1171:1180 topological regulation 1159:1180 topological regulation of transmembrane proteins 1159:1206 Our findings suggest that N-linked glycans, although synthesized in the lumens, may be exposed to cytosol through retrotranslocation, a reaction that may play a crucial role in topological regulation of transmembrane proteins. 36972171 4 4 theme ER-associated 735:747 arg1 degradation 749:759 ER-associated degradation 735:759 ER-associated degradation 735:759 In the absence of ceramide, the sequence surrounding glycosylated N163 but not N132 is retrotranslocated from lumen to cytosol independent of ER-associated degradation. 36972171 4 5 theme ceramide 611:618 arg1 absence 600:606 the absence 596:606 the absence of ceramide 596:618 In the absence of ceramide, the sequence surrounding glycosylated N163 but not N132 is retrotranslocated from lumen to cytosol independent of ER-associated degradation. 36972171 7 6 theme proteins 1199:1206 arg1 regulation 1171:1180 topological regulation 1159:1180 topological regulation of transmembrane proteins 1159:1206 Our findings suggest that N-linked glycans, although synthesized in the lumens, may be exposed to cytosol through retrotranslocation, a reaction that may play a crucial role in topological regulation of transmembrane proteins. 36972171 3 7 theme C 482:482 arg1 terminus 484:491 a cytosolic C terminus 470:491 a cytosolic C terminus 470:491 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 0 8 gly glycosylated 96:107 arg1 sequence 109:116 glycosylated sequence 96:116 glycosylated sequence 96:116 Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence. 36972171 4 9 theme glycosylated 646:657 arg1 N163 659:662 N163 659:662 glycosylated N163 but not N132 646:675 In the absence of ceramide, the sequence surrounding glycosylated N163 but not N132 is retrotranslocated from lumen to cytosol independent of ER-associated degradation. 36972171 6 10 theme retrotranslocation 886:903 arg1 process 905:911 the retrotranslocation process 882:911 the retrotranslocation process 882:911 Ceramide delays the retrotranslocation process, causing accumulation of the protein that is originally synthesized. 36972171 7 11 theme transmembrane 1185:1197 arg1 proteins 1199:1206 transmembrane proteins 1185:1206 transmembrane proteins 1185:1206 Our findings suggest that N-linked glycans, although synthesized in the lumens, may be exposed to cytosol through retrotranslocation, a reaction that may play a crucial role in topological regulation of transmembrane proteins. 36972171 0 12 theme Topological 0:10 arg1 regulation 12:21 Topological regulation 0:21 Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence. 0:117 Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence. 36972171 1 13 theme Transmembrane 119:131 arg1 proteins 133:140 Transmembrane proteins 119:140 Transmembrane proteins 119:140 Transmembrane proteins must adopt proper topology to perform their functions. 36972171 5 14 theme protein 822:828 arg1 terminus 806:813 the C terminus 800:813 the C terminus of the protein 800:828 Accompanying this retrotranslocation, the C terminus of the protein is relocated from cytosol to lumen. 36972171 2 15 theme protein 333:339 arg1 topology 303:310 the topology 299:310 the topology of the transmembrane protein 299:339 We previously demonstrated that ceramide regulates TM4SF20 (transmembrane 4 L6 family 20) by altering the topology of the transmembrane protein, but the underlying mechanism remains obscure. 36972171 3 16 theme cytosolic 472:480 arg1 terminus 484:491 a cytosolic C terminus 470:491 a cytosolic C terminus 470:491 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 4 17 theme independent 720:730 arg1 cytosol 712:718 cytosol 712:718 cytosol independent of ER-associated degradation 712:759 In the absence of ceramide, the sequence surrounding glycosylated N163 but not N132 is retrotranslocated from lumen to cytosol independent of ER-associated degradation. 36972171 7 18 link N-linked 1008:1015 arg1 glycans 1017:1023 N-linked glycans 1008:1023 N-linked glycans 1008:1023 Our findings suggest that N-linked glycans, although synthesized in the lumens, may be exposed to cytosol through retrotranslocation, a reaction that may play a crucial role in topological regulation of transmembrane proteins. 36972171 3 19 theme transmembrane 528:540 arg1 helix 542:546 the last transmembrane helix 519:546 the last transmembrane helix where N132, N148, and N163 are glycosylated 519:590 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 2 20 theme transmembrane 319:331 arg1 protein 333:339 the transmembrane protein 315:339 the transmembrane protein 315:339 We previously demonstrated that ceramide regulates TM4SF20 (transmembrane 4 L6 family 20) by altering the topology of the transmembrane protein, but the underlying mechanism remains obscure. 36972171 3 21 gly glycosylated 579:590 arg1 N148 560:563 N148 560:563 N148 560:563 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 3 21 gly glycosylated 579:590 arg1 N163 570:573 N163 570:573 N163 570:573 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 3 21 gly glycosylated 579:590 arg1 N132 554:557 N132 554:557 N132 554:557 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 0 22 theme protein 42:48 arg1 regulation 12:21 Topological regulation 0:21 Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence. 0:117 Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence. 36972171 3 23 theme luminal 499:505 arg1 loop 507:510 a luminal loop 497:510 a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated 497:590 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 3 24 theme endoplasmic 438:448 arg1 ER 461:462 ER 461:462 ER 461:462 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 3 24 theme endoplasmic 438:448 arg1 reticulum 450:458 the endoplasmic reticulum 434:458 the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated 434:590 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 0 25 theme transmembrane 28:40 arg1 protein 42:48 a transmembrane protein 26:48 a transmembrane protein 26:48 Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence. 36972171 2 26 theme L6 273:274 arg1 family 276:281 transmembrane 4 L6 family 20 257:284 transmembrane 4 L6 family 20 257:284 We previously demonstrated that ceramide regulates TM4SF20 (transmembrane 4 L6 family 20) by altering the topology of the transmembrane protein, but the underlying mechanism remains obscure. 36972171 2 26 theme L6 273:274 arg1 TM4SF20 248:254 TM4SF20 248:254 TM4SF20 (transmembrane 4 L6 family 20) 248:285 We previously demonstrated that ceramide regulates TM4SF20 (transmembrane 4 L6 family 20) by altering the topology of the transmembrane protein, but the underlying mechanism remains obscure. 36972171 0 27 theme luminal-to-cytosolic 53:72 arg1 retrotranslocation 74:91 luminal-to-cytosolic retrotranslocation 53:91 luminal-to-cytosolic retrotranslocation of glycosylated sequence 53:116 Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence. 36972171 3 28 with reticulum 450:458 arg1 terminus 484:491 a cytosolic C terminus 470:491 a cytosolic C terminus 470:491 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 3 28 with reticulum 450:458 arg1 loop 507:510 a luminal loop 497:510 a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated 497:590 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 36972171 7 29 dep exposed 1069:1075 arg1 synthesized 1035:1045 synthesized 1035:1045 synthesized in the lumens 1035:1059 Our findings suggest that N-linked glycans, although synthesized in the lumens, may be exposed to cytosol through retrotranslocation, a reaction that may play a crucial role in topological regulation of transmembrane proteins. 36972171 7 30 theme crucial 1143:1149 arg1 role 1151:1154 a crucial role 1141:1154 a crucial role 1141:1154 Our findings suggest that N-linked glycans, although synthesized in the lumens, may be exposed to cytosol through retrotranslocation, a reaction that may play a crucial role in topological regulation of transmembrane proteins. 36972171 2 31 theme transmembrane 257:269 arg1 family 276:281 transmembrane 4 L6 family 20 257:284 transmembrane 4 L6 family 20 257:284 We previously demonstrated that ceramide regulates TM4SF20 (transmembrane 4 L6 family 20) by altering the topology of the transmembrane protein, but the underlying mechanism remains obscure. 36972171 2 31 theme transmembrane 257:269 arg1 TM4SF20 248:254 TM4SF20 248:254 TM4SF20 (transmembrane 4 L6 family 20) 248:285 We previously demonstrated that ceramide regulates TM4SF20 (transmembrane 4 L6 family 20) by altering the topology of the transmembrane protein, but the underlying mechanism remains obscure. 36972171 1 32 theme proper 153:158 arg1 topology 160:167 proper topology 153:167 proper topology 153:167 Transmembrane proteins must adopt proper topology to perform their functions. 36972171 6 33 theme protein 942:948 arg1 accumulation 922:933 accumulation 922:933 accumulation of the protein that is originally synthesized 922:979 Ceramide delays the retrotranslocation process, causing accumulation of the protein that is originally synthesized. 36972171 2 34 theme underlying 350:359 arg1 mechanism 361:369 the underlying mechanism 346:369 the underlying mechanism 346:369 We previously demonstrated that ceramide regulates TM4SF20 (transmembrane 4 L6 family 20) by altering the topology of the transmembrane protein, but the underlying mechanism remains obscure. 36972171 4 35 theme degradation 749:759 arg1 independent 720:730 independent 720:730 independent 720:730 In the absence of ceramide, the sequence surrounding glycosylated N163 but not N132 is retrotranslocated from lumen to cytosol independent of ER-associated degradation. 36972171 7 36 theme N-linked 1008:1015 arg1 glycans 1017:1023 N-linked glycans 1008:1023 N-linked glycans 1008:1023 Our findings suggest that N-linked glycans, although synthesized in the lumens, may be exposed to cytosol through retrotranslocation, a reaction that may play a crucial role in topological regulation of transmembrane proteins. 36972171 5 37 theme C 804:804 arg1 terminus 806:813 the C terminus 800:813 the C terminus of the protein 800:828 Accompanying this retrotranslocation, the C terminus of the protein is relocated from cytosol to lumen. 36972171 3 38 theme last 523:526 arg1 helix 542:546 the last transmembrane helix 519:546 the last transmembrane helix where N132, N148, and N163 are glycosylated 519:590 Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. 35891957 1 0 theme polyvinyl 304:312 arg1 alcohol 314:320 polyvinyl alcohol 304:320 polyvinyl alcohol 304:320 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 2 1 theme /carboxymethyl 571:584 arg1 /tetracycline 625:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline 548:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) 548:643 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 2 1 theme /carboxymethyl 571:584 arg1 Tet 640:642 Tet 640:642 Tet 640:642 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 1 2 theme natural 159:165 arg1 polymers 229:236 natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers 159:236 natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) 159:321 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 1 2 theme natural 159:165 arg1 polymers 119:126 The most common polymers 103:126 The most common polymers in the treatment of wounds 103:153 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 9 3 theme surface 1525:1531 arg1 morphology 1533:1542 surface morphology 1525:1542 surface morphology 1525:1542 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 1 4 dep acid 259:262 arg1 e.g. 239:242 e.g. 239:242 e.g. 239:242 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 2 5 theme PAMAM 619:623 arg1 /tetracycline 625:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline 548:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) 548:643 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 2 5 theme PAMAM 619:623 arg1 Tet 640:642 Tet 640:642 Tet 640:642 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 6 6 theme different 1022:1030 arg1 tetracycline 1058:1069 the antibiotic tetracycline 1043:1069 the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) 1043:1100 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 6 6 theme different 1022:1030 arg1 amounts 1032:1038 different amounts 1022:1038 different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) 1022:1100 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 4 7 theme composite 799:807 arg1 nanofiber 809:817 the composite nanofiber 795:817 the composite nanofiber 795:817 Materials and Methods The morphology of the composite nanofiber was studied by a field emission scanning electron microscope. 35891957 10 8 theme spectroscopy 1617:1628 arg1 results 1601:1607 The results 1597:1607 The results of FTIR spectroscopy 1597:1628 The results of FTIR spectroscopy indicated that the tetracycline and polyamidoamine were successfully placed in nanofibers. 35891957 9 9 theme drug 1483:1486 arg1 release 1488:1494 the drug release 1479:1494 the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet 1479:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 10 theme PVA/CMC/15 1499:1508 arg1 % 1509:1509 % 1509:1509 % 1509:1509 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 4 11 theme nanofiber 809:817 arg1 morphology 781:790 Materials and Methods The morphology 755:790 Materials and Methods The morphology of the composite nanofiber 755:817 Materials and Methods The morphology of the composite nanofiber was studied by a field emission scanning electron microscope. 35891957 2 12 theme amine 612:616 arg1 /tetracycline 625:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline 548:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) 548:643 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 2 12 theme amine 612:616 arg1 Tet 640:642 Tet 640:642 Tet 640:642 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 6 13 theme amounts 1032:1038 arg1 release 1011:1017 the release 1007:1017 the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) 1007:1100 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 8 14 contain containing 1365:1374 arg1 those 1359:1363 those 1359:1363 those 1359:1363 It was found that nanofiber membranes loaded with 1%, 3%, and 5% tetracycline released drugs for over 28 days, while those containing 7% tetracycline released drugs for more than 14 days. 35891957 8 14 contain containing 1365:1374 arg2 tetracycline 1379:1390 7% tetracycline 1376:1390 7% tetracycline 1376:1390 It was found that nanofiber membranes loaded with 1%, 3%, and 5% tetracycline released drugs for over 28 days, while those containing 7% tetracycline released drugs for more than 14 days. 35891957 1 15 theme poly-glycolic 245:257 arg1 acid 259:262 poly-glycolic acid 245:262 poly-glycolic acid 245:262 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 3 16 theme antibacterial 669:681 arg1 effect 683:688 The antibacterial effect 665:688 The antibacterial effect of PAMAM 665:697 The antibacterial effect of PAMAM was also tested against E. coli and S. aureus bacteria. 35891957 2 17 theme /polyamide 601:610 arg1 /tetracycline 625:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline 548:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) 548:643 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 2 17 theme /polyamide 601:610 arg1 Tet 640:642 Tet 640:642 Tet 640:642 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 6 18 theme wound 1119:1123 arg1 infection 1125:1133 wound infection 1119:1133 wound infection 1119:1133 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 8 19 theme 7 1376:1376 arg1 % 1377:1377 % 1377:1377 % 1377:1377 It was found that nanofiber membranes loaded with 1%, 3%, and 5% tetracycline released drugs for over 28 days, while those containing 7% tetracycline released drugs for more than 14 days. 35891957 2 20 theme CMC 597:599 arg1 /tetracycline 625:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline 548:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) 548:643 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 2 20 theme CMC 597:599 arg1 Tet 640:642 Tet 640:642 Tet 640:642 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 9 21 theme Tet 1585:1587 arg1 Tet 1585:1587 Tet 1585:1587 Tet 1585:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 21 theme Tet 1585:1587 arg1 amount 1575:1580 the optimal amount 1563:1580 the optimal amount of Tet 1563:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 21 theme Tet 1585:1587 arg1 PAMAM/Tet 1511:1519 PVA/CMC/15% PAMAM/Tet 1499:1519 PVA/CMC/15% PAMAM/Tet 1499:1519 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 22 theme % 1509:1509 arg1 Tet 1585:1587 Tet 1585:1587 Tet 1585:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 22 theme % 1509:1509 arg1 amount 1575:1580 the optimal amount 1563:1580 the optimal amount of Tet 1563:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 22 theme % 1509:1509 arg1 PAMAM/Tet 1511:1519 PVA/CMC/15% PAMAM/Tet 1499:1519 PVA/CMC/15% PAMAM/Tet 1499:1519 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 1 23 theme human 440:444 arg1 body 446:449 the human body 436:449 the human body 436:449 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 1 24 dep natural 159:165 arg1 polysaccharides 174:188 polysaccharides 174:188 polysaccharides 174:188 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 1 24 dep natural 159:165 arg1 proteins 191:198 proteins 191:198 proteins 191:198 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 1 24 dep natural 159:165 arg1 peptides 205:212 peptides 205:212 peptides 205:212 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 2 25 dep Objectives 452:461 arg1 aimed 481:485 aimed 481:485 aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound 481:662 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 7 26 theme nanofibers 1199:1208 arg1 release 1184:1190 the highest-profile release 1164:1190 the highest-profile release of all nanofibers 1164:1208 The findings indicated that the highest-profile release of all nanofibers occurred early within 12 hours. 35891957 3 27 theme PAMAM 693:697 arg1 effect 683:688 The antibacterial effect 665:688 The antibacterial effect of PAMAM 665:697 The antibacterial effect of PAMAM was also tested against E. coli and S. aureus bacteria. 35891957 2 28 theme cellulose 586:594 arg1 /tetracycline 625:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline 548:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) 548:643 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 2 28 theme cellulose 586:594 arg1 Tet 640:642 Tet 640:642 Tet 640:642 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 2 29 theme /tetracycline 625:637 arg1 nanofibers 534:543 the nanofibers 530:543 the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) 530:643 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 5 30 theme Infrared 881:888 arg1 spectroscopy 890:901 Infrared spectroscopy 881:901 Infrared spectroscopy (FTIR) was 881:912 Infrared spectroscopy (FTIR) was used to characterize the nano chemical structure. 35891957 5 30 theme Infrared 881:888 arg1 FTIR 904:907 FTIR 904:907 FTIR 904:907 Infrared spectroscopy (FTIR) was used to characterize the nano chemical structure. 35891957 8 31 theme % 1377:1377 arg1 tetracycline 1379:1390 7% tetracycline 1376:1390 7% tetracycline 1376:1390 It was found that nanofiber membranes loaded with 1%, 3%, and 5% tetracycline released drugs for over 28 days, while those containing 7% tetracycline released drugs for more than 14 days. 35891957 4 32 theme scanning 851:858 arg1 microscope 869:878 a field emission scanning electron microscope 834:878 a field emission scanning electron microscope 834:878 Materials and Methods The morphology of the composite nanofiber was studied by a field emission scanning electron microscope. 35891957 1 33 theme common 112:117 arg1 polymers 229:236 natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers 159:236 natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) 159:321 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 1 33 theme common 112:117 arg1 polymers 119:126 The most common polymers 103:126 The most common polymers in the treatment of wounds 103:153 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 5 34 theme chemical 944:951 arg1 structure 953:961 the nano chemical structure 935:961 the nano chemical structure 935:961 Infrared spectroscopy (FTIR) was used to characterize the nano chemical structure. 35891957 5 35 used used 914:917 arg2  was 909:912 Infrared spectroscopy (FTIR) was 881:912 Infrared spectroscopy (FTIR) was 881:912 Infrared spectroscopy (FTIR) was used to characterize the nano chemical structure. 35891957 1 36 theme polyacrylic 265:275 arg1 acid 277:280 polyacrylic acid 265:280 polyacrylic acid 265:280 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 4 37 theme emission 842:849 arg1 microscope 869:878 a field emission scanning electron microscope 834:878 a field emission scanning electron microscope 834:878 Materials and Methods The morphology of the composite nanofiber was studied by a field emission scanning electron microscope. 35891957 3 38 dep coli 726:729 arg1 bacteria 745:752 bacteria 745:752 bacteria 745:752 The antibacterial effect of PAMAM was also tested against E. coli and S. aureus bacteria. 35891957 9 39 theme nanofibers 1551:1560 arg1 morphology 1533:1542 surface morphology 1525:1542 surface morphology 1525:1542 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 39 theme nanofibers 1551:1560 arg1 Tet 1585:1587 Tet 1585:1587 Tet 1585:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 39 theme nanofibers 1551:1560 arg1 amount 1575:1580 the optimal amount 1563:1580 the optimal amount of Tet 1563:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 39 theme nanofibers 1551:1560 arg1 PAMAM/Tet 1511:1519 PVA/CMC/15% PAMAM/Tet 1499:1519 PVA/CMC/15% PAMAM/Tet 1499:1519 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 0 40 theme Nanofibers 52:61 arg1 Optimization 0:11 Optimization 0:11 Optimization of Dendrimer Polyamidoamin Electrospun Nanofibers: Preparation and Properties. 0:90 Optimization of Dendrimer Polyamidoamin Electrospun Nanofibers: Preparation and Properties. 35891957 9 41 theme morphology 1533:1542 arg1 release 1488:1494 the drug release 1479:1494 the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet 1479:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 42 theme PAMAM/Tet 1511:1519 arg1 release 1488:1494 the drug release 1479:1494 the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet 1479:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 1 43 dep polysaccharides 174:188 arg1 e.g. 168:171 e.g. 168:171 e.g. 168:171 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 7 44 theme highest-profile 1168:1182 arg1 release 1184:1190 the highest-profile release 1164:1190 the highest-profile release of all nanofibers 1164:1208 The findings indicated that the highest-profile release of all nanofibers occurred early within 12 hours. 35891957 2 45 theme electrospinning 501:515 arg1 method 517:522 an electrospinning method 498:522 an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound 498:662 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 8 46 theme % 1305:1305 arg1 tetracycline 1307:1318 5% tetracycline 1304:1318 5% tetracycline 1304:1318 It was found that nanofiber membranes loaded with 1%, 3%, and 5% tetracycline released drugs for over 28 days, while those containing 7% tetracycline released drugs for more than 14 days. 35891957 1 47 theme polylactic 283:292 arg1 acid 294:297 polylactic acid 283:297 polylactic acid 283:297 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 2 48 theme alcohol 558:564 arg1 /tetracycline 625:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline 548:637 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) 548:643 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 2 48 theme alcohol 558:564 arg1 Tet 640:642 Tet 640:642 Tet 640:642 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 8 49 theme 5 1304:1304 arg1 % 1305:1305 % 1305:1305 % 1305:1305 It was found that nanofiber membranes loaded with 1%, 3%, and 5% tetracycline released drugs for over 28 days, while those containing 7% tetracycline released drugs for more than 14 days. 35891957 4 50 theme electron 860:867 arg1 microscope 869:878 a field emission scanning electron microscope 834:878 a field emission scanning electron microscope 834:878 Materials and Methods The morphology of the composite nanofiber was studied by a field emission scanning electron microscope. 35891957 4 51 theme Methods 769:775 arg1 morphology 781:790 Materials and Methods The morphology 755:790 Materials and Methods The morphology of the composite nanofiber 755:817 Materials and Methods The morphology of the composite nanofiber was studied by a field emission scanning electron microscope. 35891957 2 52 theme polyvinyl 548:556 arg1 PVA 567:569 PVA 567:569 PVA 567:569 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 2 52 theme polyvinyl 548:556 arg1 alcohol 558:564 polyvinyl alcohol 548:564 polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) 548:643 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 4 53 theme Materials 755:763 arg1 morphology 781:790 Materials and Methods The morphology 755:790 Materials and Methods The morphology of the composite nanofiber 755:817 Materials and Methods The morphology of the composite nanofiber was studied by a field emission scanning electron microscope. 35891957 1 54 dep Background 92:101 arg1 polymers 229:236 natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers 159:236 natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) 159:321 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 1 54 dep Background 92:101 arg1 polymers 119:126 The most common polymers 103:126 The most common polymers in the treatment of wounds 103:153 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 5 55 theme nano 939:942 arg1 structure 953:961 the nano chemical structure 935:961 the nano chemical structure 935:961 Infrared spectroscopy (FTIR) was used to characterize the nano chemical structure. 35891957 4 56 theme field 836:840 arg1 microscope 869:878 a field emission scanning electron microscope 834:878 a field emission scanning electron microscope 834:878 Materials and Methods The morphology of the composite nanofiber was studied by a field emission scanning electron microscope. 35891957 1 57 theme structural 382:391 arg1 resemblance 393:403 their structural resemblance 376:403 their structural resemblance to the macromolecules known to the human body 376:449 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 6 58 dep tetracycline 1058:1069 arg1 % 1089:1089 7% 1088:1089 7% 1088:1089 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 6 58 dep tetracycline 1058:1069 arg1 % 1073:1073 1% 1072:1073 1% 1072:1073 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 6 58 dep tetracycline 1058:1069 arg1 % 1077:1077 3% 1076:1077 3% 1076:1077 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 6 58 dep tetracycline 1058:1069 arg1 % 1081:1081 5% 1080:1081 5% 1080:1081 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 9 59 theme related 1468:1474 arg1 findings 1459:1466 the findings 1455:1466 the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet 1455:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 6 60 theme tetracycline 1058:1069 arg1 tetracycline 1058:1069 the antibiotic tetracycline 1043:1069 the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) 1043:1100 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 6 60 theme tetracycline 1058:1069 arg1 amounts 1032:1038 different amounts 1022:1038 different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) 1022:1100 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 1 61 from polymers 119:126 arg1 treatment 135:143 the treatment 131:143 the treatment of wounds 131:153 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 5 62 theme spectroscopy 890:901 arg1  was 909:912 Infrared spectroscopy (FTIR) was 881:912 Infrared spectroscopy (FTIR) was 881:912 Infrared spectroscopy (FTIR) was used to characterize the nano chemical structure. 35891957 6 63 theme antibiotic 1047:1056 arg1 tetracycline 1058:1069 the antibiotic tetracycline 1043:1069 the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) 1043:1100 Results Nanofibers were evaluated based on the release of different amounts of the antibiotic tetracycline (1%, 3%, 5%, and 7% by weight) while preventing wound infection. 35891957 9 64 theme optimal 1567:1573 arg1 Tet 1585:1587 Tet 1585:1587 Tet 1585:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 64 theme optimal 1567:1573 arg1 amount 1575:1580 the optimal amount 1563:1580 the optimal amount of Tet 1563:1587 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 9 64 theme optimal 1567:1573 arg1 PAMAM/Tet 1511:1519 PVA/CMC/15% PAMAM/Tet 1499:1519 PVA/CMC/15% PAMAM/Tet 1499:1519 Conclusions According to the findings related to the drug release of PVA/CMC/15% PAMAM/Tet and surface morphology of the nanofibers, the optimal amount of Tet was 5%. 35891957 8 65 theme nanofiber 1260:1268 arg1 membranes 1270:1278 nanofiber membranes 1260:1278 nanofiber membranes loaded with 1%, 3%, and 5% tetracycline 1260:1318 It was found that nanofiber membranes loaded with 1%, 3%, and 5% tetracycline released drugs for over 28 days, while those containing 7% tetracycline released drugs for more than 14 days. 35891957 1 66 theme wounds 148:153 arg1 treatment 135:143 the treatment 131:143 the treatment of wounds 131:153 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 1 67 theme synthetic 219:227 arg1 polymers 229:236 natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers 159:236 natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) 159:321 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 1 67 theme synthetic 219:227 arg1 polymers 119:126 The most common polymers 103:126 The most common polymers in the treatment of wounds 103:153 Background The most common polymers in the treatment of wounds are natural (e.g., polysaccharides, proteins, and peptides) and synthetic polymers (e.g., poly-glycolic acid, polyacrylic acid, polylactic acid, and polyvinyl alcohol) due to their biodegradability, biocompatibility, and their structural resemblance to the macromolecules known to the human body. 35891957 2 68 theme current 467:473 arg1 study 475:479 The current study 463:479 The current study 463:479 Objectives The current study aimed to develop an electrospinning method using the nanofibers of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyamide amine (PAMAM)/tetracycline (Tet) to cover the wound. 35891957 0 69 dep Optimization 0:11 arg1 Properties 80:89 Properties 80:89 Properties 80:89 Optimization of Dendrimer Polyamidoamin Electrospun Nanofibers: Preparation and Properties. 35891957 0 69 dep Optimization 0:11 arg1 Preparation 64:74 Preparation 64:74 Preparation 64:74 Optimization of Dendrimer Polyamidoamin Electrospun Nanofibers: Preparation and Properties. 35891957 10 70 theme FTIR 1612:1615 arg1 spectroscopy 1617:1628 FTIR spectroscopy 1612:1628 FTIR spectroscopy 1612:1628 The results of FTIR spectroscopy indicated that the tetracycline and polyamidoamine were successfully placed in nanofibers. 35877898 0 0 theme Carbon 76:81 arg1 Dots 91:94 Green Carbon Quantum Dots 70:94 Green Carbon Quantum Dots 70:94 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 2 1 theme stronger 473:480 arg1 links 492:496 stronger molecular links 473:496 stronger molecular links 473:496 The resulting films have, however, limits associated with the resistance to mechanical stress; therefore, it is important to reinforce the initial mixture with additives that promote the development of stronger molecular links. 35877898 2 2 theme mechanical 347:356 arg1 stress 358:363 mechanical stress 347:363 mechanical stress 347:363 The resulting films have, however, limits associated with the resistance to mechanical stress; therefore, it is important to reinforce the initial mixture with additives that promote the development of stronger molecular links. 35877898 4 3 theme mechanical 766:775 arg1 properties 777:786 the mechanical properties 762:786 the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers 762:905 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 0 4 theme Green 70:74 arg1 Dots 91:94 Green Carbon Quantum Dots 70:94 Green Carbon Quantum Dots 70:94 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 3 5 theme Carbon 499:504 arg1 CDs 512:514 CDs 512:514 CDs 512:514 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 3 5 theme Carbon 499:504 arg1 dots 506:509 Carbon dots 499:509 Carbon dots (CDs) 499:515 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 3 5 theme Carbon 499:504 arg1 candidates 531:540 excellent candidates 521:540 excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers 521:700 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 1 6 theme food 255:258 arg1 packaging 260:268 food packaging 255:268 food packaging 255:268 Nowadays, proteins and polysaccharides play a fundamental role in the manufacturing of biocompatible materials applied in food packaging. 35877898 8 7 theme dispersions 1503:1513 arg1 viscosity 1463:1471 the viscosity 1459:1471 the viscosity of the protein-polysaccharide dispersions 1459:1513 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 4 8 theme methoxyl 851:858 arg1 HMP 868:870 HMP 868:870 HMP 868:870 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 4 8 theme methoxyl 851:858 arg1 pectin 860:865 high methoxyl pectin 846:865 high methoxyl pectin (HMP) 846:871 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 6 9 theme corresponded 1138:1149 arg1 films 1151:1155 the corresponded films 1134:1155 the corresponded films 1134:1155 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 5 10 theme carbon 914:919 arg1 gCDs 927:930 gCDs 927:930 gCDs 927:930 Green carbon dots (gCDs) were obtained from natural organic sources by green synthesis. 35877898 5 10 theme carbon 914:919 arg1 dots 921:924 Green carbon dots 908:924 Green carbon dots (gCDs) 908:931 Green carbon dots (gCDs) were obtained from natural organic sources by green synthesis. 35877898 6 11 theme shear 1195:1199 arg1 measurements 1213:1224 steady and unsteady shear rheological measurements 1175:1224 measurements 1213:1224 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 0 12 theme Quantum 83:89 arg1 Dots 91:94 Green Carbon Quantum Dots 70:94 Green Carbon Quantum Dots 70:94 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 8 13 theme thermomechanical 1523:1538 arg1 properties 1540:1549 the thermomechanical properties 1519:1549 the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs 1519:1622 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 4 14 theme high 846:849 arg1 HMP 868:870 HMP 868:870 HMP 868:870 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 4 14 theme high 846:849 arg1 pectin 860:865 high methoxyl pectin 846:865 high methoxyl pectin (HMP) 846:871 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 6 15 theme scanning 1243:1250 arg1 calorimetry 1252:1262 differential scanning calorimetry 1230:1262 differential scanning calorimetry (DSC) tests 1230:1274 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 15 theme scanning 1243:1250 arg1 DSC 1265:1267 DSC 1265:1267 DSC 1265:1267 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 3 16 theme excellent 521:529 arg1 dots 506:509 Carbon dots 499:509 Carbon dots (CDs) 499:515 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 3 16 theme excellent 521:529 arg1 candidates 531:540 excellent candidates 521:540 excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers 521:700 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 0 17 theme Rheological 97:107 arg1 Studies 124:130 Rheological and Mechanical Studies 97:130 Rheological and Mechanical Studies 97:130 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 6 18 theme differential 1230:1241 arg1 calorimetry 1252:1262 differential scanning calorimetry 1230:1262 differential scanning calorimetry (DSC) tests 1230:1274 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 18 theme differential 1230:1241 arg1 DSC 1265:1267 DSC 1265:1267 DSC 1265:1267 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 4 19 from effect 745:750 arg1 properties 777:786 the mechanical properties 762:786 the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers 762:905 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 2 20 theme resulting 275:283 arg1 films 285:289 The resulting films 271:289 The resulting films 271:289 The resulting films have, however, limits associated with the resistance to mechanical stress; therefore, it is important to reinforce the initial mixture with additives that promote the development of stronger molecular links. 35877898 6 21 from properties 1120:1129 arg1 behavior 1028:1035 the flow behavior 1019:1035 the flow behavior 1019:1035 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 7 22 theme dynamic 1295:1301 arg1 measurements 1314:1325 The dynamic mechanical measurements 1291:1325 The dynamic mechanical measurements 1291:1325 The dynamic mechanical measurements were realized taking into account the parameters of temperature and relative humidity. 35877898 4 23 theme sodium 822:827 arg1 CAS 840:842 CAS 840:842 CAS 840:842 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 4 23 theme sodium 822:827 arg1 caseinate 829:837 sodium caseinate 822:837 sodium caseinate (CAS) 822:843 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 4 24 theme CDs 755:757 arg1 effect 745:750 the effect 741:750 the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers 741:905 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 6 25 theme flow 1023:1026 arg1 behavior 1028:1035 the flow behavior 1019:1035 the flow behavior 1019:1035 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 7 26 theme mechanical 1303:1312 arg1 measurements 1314:1325 The dynamic mechanical measurements 1291:1325 The dynamic mechanical measurements 1291:1325 The dynamic mechanical measurements were realized taking into account the parameters of temperature and relative humidity. 35877898 0 27 theme Methoxyl 5:12 arg1 Pectin 14:19 High Methoxyl Pectin 0:19 High Methoxyl Pectin 0:19 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 8 28 theme film 1572:1575 arg1 samples 1577:1583 the corresponding film samples 1554:1583 the corresponding film samples reinforced with higher amounts of gCDs 1554:1622 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 8 29 from change 1449:1454 arg1 viscosity 1463:1471 the viscosity 1459:1471 the viscosity of the protein-polysaccharide dispersions 1459:1513 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 6 30 theme thermophysical 1105:1118 arg1 properties 1120:1129 the thermophysical properties 1101:1129 the thermophysical properties of the corresponded films 1101:1155 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 31 theme gCDs 1011:1014 arg1 effects 1000:1006 The effects 996:1006 The effects of gCDs on the flow behavior 996:1035 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 31 theme gCDs 1011:1014 arg1 properties 1120:1129 the thermophysical properties 1101:1129 the thermophysical properties of the corresponded films 1101:1155 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 31 theme gCDs 1011:1014 arg1 properties 1054:1063 viscoelastic properties 1041:1063 viscoelastic properties 1041:1063 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 0 32 theme High 0:3 arg1 Pectin 14:19 High Methoxyl Pectin 0:19 High Methoxyl Pectin 0:19 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 8 33 theme corresponding 1558:1570 arg1 samples 1577:1583 the corresponding film samples 1554:1583 the corresponding film samples reinforced with higher amounts of gCDs 1554:1622 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 6 34 theme rheological 1201:1211 arg1 measurements 1213:1224 steady and unsteady shear rheological measurements 1175:1224 measurements 1213:1224 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 35 from effects 1000:1006 arg1 behavior 1028:1035 the flow behavior 1019:1035 the flow behavior 1019:1035 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 7 36 theme relative 1395:1402 arg1 humidity 1404:1411 relative humidity 1395:1411 relative humidity 1395:1411 The dynamic mechanical measurements were realized taking into account the parameters of temperature and relative humidity. 35877898 1 37 theme fundamental 179:189 arg1 role 191:194 a fundamental role 177:194 a fundamental role 177:194 Nowadays, proteins and polysaccharides play a fundamental role in the manufacturing of biocompatible materials applied in food packaging. 35877898 0 38 theme Mechanical 113:122 arg1 Studies 124:130 Rheological and Mechanical Studies 97:130 Rheological and Mechanical Studies 97:130 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 6 39 theme dispersions 1085:1095 arg1 effects 1000:1006 The effects 996:1006 The effects of gCDs on the flow behavior 996:1035 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 39 theme dispersions 1085:1095 arg1 properties 1120:1129 the thermophysical properties 1101:1129 the thermophysical properties of the corresponded films 1101:1155 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 39 theme dispersions 1085:1095 arg1 properties 1054:1063 viscoelastic properties 1041:1063 viscoelastic properties 1041:1063 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 5 40 theme Green 908:912 arg1 gCDs 927:930 gCDs 927:930 gCDs 927:930 Green carbon dots (gCDs) were obtained from natural organic sources by green synthesis. 35877898 5 40 theme Green 908:912 arg1 dots 921:924 Green carbon dots 908:924 Green carbon dots (gCDs) 908:931 Green carbon dots (gCDs) were obtained from natural organic sources by green synthesis. 35877898 5 41 theme organic 960:966 arg1 sources 968:974 natural organic sources 952:974 natural organic sources 952:974 Green carbon dots (gCDs) were obtained from natural organic sources by green synthesis. 35877898 2 42 theme initial 410:416 arg1 mixture 418:424 the initial mixture 406:424 the initial mixture with additives that promote the development of stronger molecular links 406:496 The resulting films have, however, limits associated with the resistance to mechanical stress; therefore, it is important to reinforce the initial mixture with additives that promote the development of stronger molecular links. 35877898 8 43 theme samples 1577:1583 arg1 change 1449:1454 a significant change 1435:1454 a significant change in the viscosity of the protein-polysaccharide dispersions 1435:1513 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 8 43 theme samples 1577:1583 arg1 properties 1540:1549 the thermomechanical properties 1519:1549 the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs 1519:1622 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 7 44 theme humidity 1404:1411 arg1 parameters 1365:1374 the parameters 1361:1374 the parameters of temperature and relative humidity 1361:1411 The dynamic mechanical measurements were realized taking into account the parameters of temperature and relative humidity. 35877898 0 45 dep Reinforced 54:63 arg1 Studies 124:130 Rheological and Mechanical Studies 97:130 Rheological and Mechanical Studies 97:130 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 0 46 theme Caseinate 32:40 arg1 Matrix 47:52 Sodium Caseinate Film Matrix 25:52 Sodium Caseinate Film Matrix 25:52 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 2 47 contain have 291:294 arg1 films 285:289 The resulting films 271:289 The resulting films 271:289 The resulting films have, however, limits associated with the resistance to mechanical stress; therefore, it is important to reinforce the initial mixture with additives that promote the development of stronger molecular links. 35877898 2 47 contain have 291:294 arg2 limits 306:311 limits 306:311 limits associated with the resistance to mechanical stress 306:363 The resulting films have, however, limits associated with the resistance to mechanical stress; therefore, it is important to reinforce the initial mixture with additives that promote the development of stronger molecular links. 35877898 6 48 theme mixed 1068:1072 arg1 dispersions 1085:1095 mixed biopolymer dispersions 1068:1095 mixed biopolymer dispersions 1068:1095 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 4 49 theme films 802:806 arg1 properties 777:786 the mechanical properties 762:786 the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers 762:905 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 6 50 theme films 1151:1155 arg1 effects 1000:1006 The effects 996:1006 The effects of gCDs on the flow behavior 996:1035 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 50 theme films 1151:1155 arg1 properties 1120:1129 the thermophysical properties 1101:1129 the thermophysical properties of the corresponded films 1101:1155 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 50 theme films 1151:1155 arg1 properties 1054:1063 viscoelastic properties 1041:1063 viscoelastic properties 1041:1063 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 0 51 theme Sodium 25:30 arg1 Matrix 47:52 Sodium Caseinate Film Matrix 25:52 Sodium Caseinate Film Matrix 25:52 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 8 52 from properties 1540:1549 arg1 viscosity 1463:1471 the viscosity 1459:1471 the viscosity of the protein-polysaccharide dispersions 1459:1513 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 4 53 theme biopolymer 791:800 arg1 films 802:806 biopolymer films 791:806 biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers 791:905 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 2 54 with mixture 418:424 arg1 additives 431:439 additives 431:439 additives that promote the development of stronger molecular links 431:496 The resulting films have, however, limits associated with the resistance to mechanical stress; therefore, it is important to reinforce the initial mixture with additives that promote the development of stronger molecular links. 35877898 8 55 theme higher 1601:1606 arg1 gCDs 1619:1622 gCDs 1619:1622 gCDs 1619:1622 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 8 55 theme higher 1601:1606 arg1 amounts 1608:1614 higher amounts 1601:1614 higher amounts of gCDs 1601:1622 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 8 56 theme significant 1437:1447 arg1 change 1449:1454 a significant change 1435:1454 a significant change in the viscosity of the protein-polysaccharide dispersions 1435:1513 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 3 57 theme due 559:561 arg1 purpose 551:557 this purpose 546:557 this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers 546:700 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 6 58 from properties 1054:1063 arg1 behavior 1028:1035 the flow behavior 1019:1035 the flow behavior 1019:1035 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 59 theme biopolymer 1074:1083 arg1 dispersions 1085:1095 mixed biopolymer dispersions 1068:1095 mixed biopolymer dispersions 1068:1095 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 0 60 theme Film 42:45 arg1 Matrix 47:52 Sodium Caseinate Film Matrix 25:52 Sodium Caseinate Film Matrix 25:52 High Methoxyl Pectin and Sodium Caseinate Film Matrix Reinforced with Green Carbon Quantum Dots: Rheological and Mechanical Studies. 35877898 8 61 theme protein-polysaccharide 1480:1501 arg1 dispersions 1503:1513 the protein-polysaccharide dispersions 1476:1513 the protein-polysaccharide dispersions 1476:1513 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 3 62 theme intramolecular 649:662 arg1 bonds 664:668 numerous intramolecular bonds 640:668 numerous intramolecular bonds between the charged biopolymers 640:700 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 5 63 theme green 979:983 arg1 synthesis 985:993 green synthesis 979:993 green synthesis 979:993 Green carbon dots (gCDs) were obtained from natural organic sources by green synthesis. 35877898 6 64 theme calorimetry 1252:1262 arg1 tests 1270:1274 differential scanning calorimetry (DSC) tests 1230:1274 differential scanning calorimetry (DSC) tests 1230:1274 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 6 65 theme steady 1175:1180 arg1 measurements 1213:1224 steady and unsteady shear rheological measurements 1175:1224 measurements 1213:1224 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 5 66 theme natural 952:958 arg1 sources 968:974 natural organic sources 952:974 natural organic sources 952:974 Green carbon dots (gCDs) were obtained from natural organic sources by green synthesis. 35877898 3 67 theme bonds 664:668 arg1 formation 627:635 the formation 623:635 the formation of numerous intramolecular bonds between the charged biopolymers 623:700 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 3 68 theme functional 590:599 arg1 groups 601:606 surface functional groups 582:606 surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers 582:700 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 6 69 theme unsteady 1186:1193 arg1 measurements 1213:1224 steady and unsteady shear rheological measurements 1175:1224 measurements 1213:1224 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 7 70 theme temperature 1379:1389 arg1 parameters 1365:1374 the parameters 1361:1374 the parameters of temperature and relative humidity 1361:1411 The dynamic mechanical measurements were realized taking into account the parameters of temperature and relative humidity. 35877898 3 71 theme groups 601:606 arg1 presence 570:577 the presence 566:577 the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers 566:700 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 4 72 theme present 707:713 arg1 research 715:722 The present research 703:722 The present research 703:722 The present research aims to evaluate the effect of CDs on the mechanical properties of biopolymer films obtained from sodium caseinate (CAS), high methoxyl pectin (HMP) and glycerol used as plasticizers. 35877898 1 73 theme biocompatible 220:232 arg1 materials 234:242 biocompatible materials 220:242 biocompatible materials applied in food packaging 220:268 Nowadays, proteins and polysaccharides play a fundamental role in the manufacturing of biocompatible materials applied in food packaging. 35877898 2 74 theme links 492:496 arg1 development 458:468 the development 454:468 the development of stronger molecular links 454:496 The resulting films have, however, limits associated with the resistance to mechanical stress; therefore, it is important to reinforce the initial mixture with additives that promote the development of stronger molecular links. 35877898 3 75 theme numerous 640:647 arg1 bonds 664:668 numerous intramolecular bonds 640:668 numerous intramolecular bonds between the charged biopolymers 640:700 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 6 76 theme viscoelastic 1041:1052 arg1 properties 1054:1063 viscoelastic properties 1041:1063 viscoelastic properties 1041:1063 The effects of gCDs on the flow behavior and viscoelastic properties of mixed biopolymer dispersions and the thermophysical properties of the corresponded films were evaluated by steady and unsteady shear rheological measurements and differential scanning calorimetry (DSC) tests, respectively. 35877898 1 77 theme materials 234:242 arg1 manufacturing 203:215 the manufacturing 199:215 the manufacturing of biocompatible materials applied in food packaging 199:268 Nowadays, proteins and polysaccharides play a fundamental role in the manufacturing of biocompatible materials applied in food packaging. 35877898 2 78 theme molecular 482:490 arg1 links 492:496 stronger molecular links 473:496 stronger molecular links 473:496 The resulting films have, however, limits associated with the resistance to mechanical stress; therefore, it is important to reinforce the initial mixture with additives that promote the development of stronger molecular links. 35877898 3 79 theme charged 682:688 arg1 biopolymers 690:700 the charged biopolymers 678:700 the charged biopolymers 678:700 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 3 80 theme surface 582:588 arg1 groups 601:606 surface functional groups 582:606 surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers 582:700 Carbon dots (CDs) are excellent candidates for this purpose due to the presence of surface functional groups that determine the formation of numerous intramolecular bonds between the charged biopolymers. 35877898 8 81 theme gCDs 1619:1622 arg1 gCDs 1619:1622 gCDs 1619:1622 gCDs 1619:1622 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 35877898 8 81 theme gCDs 1619:1622 arg1 amounts 1608:1614 higher amounts 1601:1614 higher amounts of gCDs 1601:1622 The results indicate a significant change in the viscosity of the protein-polysaccharide dispersions and the thermomechanical properties of the corresponding film samples reinforced with higher amounts of gCDs. 36877384 0 0 theme ester-to-amide 81:94 arg1 derivatization 96:109 ester-to-amide derivatization 81:109 ester-to-amide derivatization 81:109 Simultaneous and sialic acid linkage-specific N- and O-linked glycan analysis by ester-to-amide derivatization. 36877384 7 1 theme sialylated 1427:1436 arg1 N- 1438:1439 N- 1438:1439 N- 1438:1439 This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins. 36877384 6 2 theme simultaneous 1186:1197 arg1 N- 1247:1248 simultaneous, quantitative, and sialic acid linkage-specific N- 1186:1248 simultaneous, quantitative, and sialic acid linkage-specific N- 1186:1248 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 6 3 theme N- 1247:1248 arg1 analyses 1270:1277 simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses 1186:1277 simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein 1186:1301 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 1 4 gly glycoproteins 184:196 arg1 glycoproteins 184:196 glycoproteins 184:196 glycoproteins 184:196 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 4 5 from residues 919:926 arg1 solid-phase 931:941 solid-phase 931:941 solid-phase 931:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 1 6 theme known 279:283 arg1 endoglycosidases 303:318 no known O-glycan-specific endoglycosidases 276:318 no known O-glycan-specific endoglycosidases 276:318 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 2 7 from termini 395:401 arg1 residues 366:373 sialic acid residues 354:373 sialic acid residues at the non-reducing termini through various linkages 354:426 Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. 36877384 3 8 link O-linked 507:514 arg1 analysis 523:530 sialic acid linkage-specific O-linked glycan analysis 478:530 sialic acid linkage-specific O-linked glycan analysis 478:530 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 6 9 link O-linked 1254:1261 arg1 glycan 1263:1268 O-linked glycan 1254:1268 O-linked glycan 1254:1268 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 4 10 theme sialic 907:912 arg1 residues 919:926 sialic acid residues 907:926 sialic acid residues on solid-phase 907:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 4 11 theme ester 891:895 arg1 groups 897:902 methyl or ethyl ester groups 875:902 methyl or ethyl ester groups of sialic acid residues on solid-phase 875:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 4 11 theme ester 891:895 arg1 residues 919:926 sialic acid residues 907:926 sialic acid residues on solid-phase 907:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 1 12 theme O-glycan-specific 285:301 arg1 endoglycosidases 303:318 no known O-glycan-specific endoglycosidases 276:318 no known O-glycan-specific endoglycosidases 276:318 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 4 13 theme ethyl 885:889 arg1 ester 891:895 methyl or ethyl ester 875:895 ester 891:895 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 7 14 theme novel 1336:1340 arg1 approach 1351:1358 This novel glycomic approach 1331:1358 This novel glycomic approach 1331:1358 This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins. 36877384 1 15 dep serine 152:157 arg1 residues 172:179 residues 172:179 residues 172:179 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 4 16 theme non-reductive 683:695 arg1 β-elimination 697:709 non-reductive β-elimination 683:709 non-reductive β-elimination 683:709 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 1 17 theme O-glycans 132:140 arg1 Characterization 112:127 Characterization 112:127 Characterization of O-glycans linked to serine or threonine residues in glycoproteins 112:196 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 5 18 theme O-glycans 1021:1029 arg1 derivatization 986:999 In-solution lactone-driven ester-to-amide derivatization 944:999 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans 944:1029 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. 36877384 1 19 from threonine 162:170 arg1 glycoproteins 184:196 glycoproteins 184:196 glycoproteins 184:196 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 2 20 theme Most 321:324 arg1 O-glycans 326:334 Most O-glycans 321:334 Most O-glycans 321:334 Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. 36877384 6 21 theme O-linked 1254:1261 arg1 glycan 1263:1268 O-linked glycan 1254:1268 O-linked glycan 1254:1268 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 6 22 theme linkage-specific 1230:1245 arg1 N- 1247:1248 simultaneous, quantitative, and sialic acid linkage-specific N- 1186:1248 simultaneous, quantitative, and sialic acid linkage-specific N- 1186:1248 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 6 23 theme model 1284:1288 arg1 glycoprotein 1290:1301 a model glycoprotein 1282:1301 a model glycoprotein 1282:1301 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 6 24 theme human 1307:1311 arg1 tissue 1323:1328 human cartilage tissue 1307:1328 human cartilage tissue 1307:1328 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 2 25 mod modified 340:347 arg1 O-glycans 326:334 Most O-glycans 321:334 Most O-glycans 321:334 Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. 36877384 2 25 mod modified 340:347 arg3 residues 366:373 sialic acid residues 354:373 sialic acid residues at the non-reducing termini through various linkages 354:426 Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. 36877384 4 26 theme acid 914:917 arg1 residues 919:926 sialic acid residues 907:926 sialic acid residues on solid-phase 907:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 3 27 theme lactone-driven 540:553 arg1 derivatization 570:583 lactone-driven ester-to-amide derivatization 540:583 lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine 540:658 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 3 28 theme sialic 478:483 arg1 acid 485:488 sialic acid 478:488 sialic acid linkage-specific O-linked glycan analysis 478:530 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 5 29 theme lactone-driven 956:969 arg1 derivatization 986:999 In-solution lactone-driven ester-to-amide derivatization 944:999 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans 944:1029 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. 36877384 6 30 theme PNGase 1151:1156 arg1 digestion 1160:1168 PNGase F digestion 1151:1168 PNGase F digestion 1151:1168 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 7 31 theme N- 1438:1439 arg1 characterization 1385:1400 detailed characterization 1376:1400 detailed characterization of biologically relevant sialylated N- and O-glycans 1376:1453 This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins. 36877384 1 32 from serine 152:157 arg1 glycoproteins 184:196 glycoproteins 184:196 glycoproteins 184:196 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 2 33 theme acid 361:364 arg1 residues 366:373 sialic acid residues 354:373 sialic acid residues at the non-reducing termini through various linkages 354:426 Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. 36877384 3 34 theme novel 459:463 arg1 approach 465:472 a novel approach 457:472 a novel approach for sialic acid linkage-specific O-linked glycan analysis 457:530 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 0 35 theme Simultaneous 0:11 arg1 N- 46:47 Simultaneous and sialic acid linkage-specific N- 0:47 Simultaneous and sialic acid linkage-specific N- 0:47 Simultaneous and sialic acid linkage-specific N- and O-linked glycan analysis by ester-to-amide derivatization. 36877384 2 36 theme sialic 354:359 arg1 residues 366:373 sialic acid residues 354:373 sialic acid residues at the non-reducing termini through various linkages 354:426 Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. 36877384 5 37 theme resulting 1054:1062 arg1 isomers 1082:1088 the resulting sialylated glycan isomers 1050:1088 the resulting sialylated glycan isomers 1050:1088 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. 36877384 5 38 theme ester-to-amide 971:984 arg1 derivatization 986:999 In-solution lactone-driven ester-to-amide derivatization 944:999 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans 944:1029 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. 36877384 4 39 theme groups 897:902 arg1 modification 859:870 modification 859:870 modification of methyl or ethyl ester groups of sialic acid residues on solid-phase 859:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 3 40 theme O-linked 507:514 arg1 analysis 523:530 sialic acid linkage-specific O-linked glycan analysis 478:530 sialic acid linkage-specific O-linked glycan analysis 478:530 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 0 41 theme sialic 17:22 arg1 acid 24:27 sialic acid 17:27 sialic acid 17:27 Simultaneous and sialic acid linkage-specific N- and O-linked glycan analysis by ester-to-amide derivatization. 36877384 6 42 theme F 1158:1158 arg1 digestion 1160:1168 PNGase F digestion 1151:1168 PNGase F digestion 1151:1168 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 4 43 theme residues 919:926 arg1 groups 897:902 methyl or ethyl ester groups 875:902 methyl or ethyl ester groups of sialic acid residues on solid-phase 875:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 4 43 theme residues 919:926 arg1 residues 919:926 sialic acid residues 907:926 sialic acid residues on solid-phase 907:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 3 44 theme hydroxylamine 646:658 arg1 presence 634:641 the presence 630:641 the presence of hydroxylamine 630:658 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 3 45 theme glycan 516:521 arg1 analysis 523:530 sialic acid linkage-specific O-linked glycan analysis 478:530 sialic acid linkage-specific O-linked glycan analysis 478:530 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 6 46 theme glycoprotein 1290:1301 arg1 tissue 1323:1328 human cartilage tissue 1307:1328 human cartilage tissue 1307:1328 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 6 46 theme glycoprotein 1290:1301 arg1 analyses 1270:1277 simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses 1186:1277 simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein 1186:1301 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 6 47 theme cartilage 1313:1321 arg1 tissue 1323:1328 human cartilage tissue 1307:1328 human cartilage tissue 1307:1328 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 7 48 gly glycoproteins 1458:1470 arg1 glycoproteins 1458:1470 glycoproteins 1458:1470 glycoproteins 1458:1470 This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins. 36877384 3 49 theme acid 485:488 arg1 analysis 523:530 sialic acid linkage-specific O-linked glycan analysis 478:530 sialic acid linkage-specific O-linked glycan analysis 478:530 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 4 50 theme chemoselective 761:774 arg1 ligation 776:783 chemoselective ligation 761:783 chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase 761:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 1 51 theme chemical 229:236 arg1 approaches 247:256 chemical reaction approaches 229:256 chemical reaction approaches 229:256 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 0 52 theme linkage-specific 29:44 arg1 N- 46:47 Simultaneous and sialic acid linkage-specific N- 0:47 Simultaneous and sialic acid linkage-specific N- 0:47 Simultaneous and sialic acid linkage-specific N- and O-linked glycan analysis by ester-to-amide derivatization. 36877384 7 53 theme glycomic 1342:1349 arg1 approach 1351:1358 This novel glycomic approach 1331:1358 This novel glycomic approach 1331:1358 This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins. 36877384 6 54 with combination 1134:1144 arg1 digestion 1160:1168 PNGase F digestion 1151:1168 PNGase F digestion 1151:1168 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 1 55 theme reaction 238:245 arg1 approaches 247:256 chemical reaction approaches 229:256 chemical reaction approaches 229:256 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 5 56 theme sialylated 1064:1073 arg1 isomers 1082:1088 the resulting sialylated glycan isomers 1050:1088 the resulting sialylated glycan isomers 1050:1088 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. 36877384 6 57 theme sialic 1218:1223 arg1 N- 1247:1248 simultaneous, quantitative, and sialic acid linkage-specific N- 1186:1248 simultaneous, quantitative, and sialic acid linkage-specific N- 1186:1248 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 7 58 gly sialylated 1427:1436 arg1 N- 1438:1439 N- 1438:1439 N- 1438:1439 This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins. 36877384 0 59 dep N- 46:47 arg1 analysis 69:76 glycan analysis 62:76 glycan analysis 62:76 Simultaneous and sialic acid linkage-specific N- and O-linked glycan analysis by ester-to-amide derivatization. 36877384 6 60 contain carried 1174:1180 arg2 analyses 1270:1277 simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses 1186:1277 simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein 1186:1301 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 6 60 contain carried 1174:1180 arg2 tissue 1323:1328 human cartilage tissue 1307:1328 human cartilage tissue 1307:1328 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 6 60 contain carried 1174:1180 arg1 we 1171:1172 we 1171:1172 we 1171:1172 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 6 60 contain carried 1174:1180 arg3 combination 1134:1144 combination 1134:1144 combination with PNGase F digestion 1134:1168 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 2 61 theme non-reducing 382:393 arg1 termini 395:401 the non-reducing termini 378:401 the non-reducing termini through various linkages 378:426 Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. 36877384 5 62 theme In-solution 944:954 arg1 derivatization 986:999 In-solution lactone-driven ester-to-amide derivatization 944:999 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans 944:1029 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. 36877384 5 63 gly sialylated 1064:1073 arg1 isomers 1082:1088 the resulting sialylated glycan isomers 1050:1088 the resulting sialylated glycan isomers 1050:1088 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. 36877384 7 64 theme relevant 1418:1425 arg1 N- 1438:1439 N- 1438:1439 N- 1438:1439 This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins. 36877384 3 65 theme ester-to-amide 555:568 arg1 derivatization 570:583 lactone-driven ester-to-amide derivatization 540:583 lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine 540:658 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 7 66 theme detailed 1376:1383 arg1 characterization 1385:1400 detailed characterization 1376:1400 detailed characterization of biologically relevant sialylated N- and O-glycans 1376:1453 This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins. 36877384 4 67 from groups 897:902 arg1 solid-phase 931:941 solid-phase 931:941 solid-phase 931:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 4 68 theme hydrazide-functionalized 813:836 arg1 polymer 838:844 a hydrazide-functionalized polymer 811:844 a hydrazide-functionalized polymer 811:844 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 4 69 theme methyl 875:880 arg1 ester 891:895 methyl or ethyl ester 875:895 ester 891:895 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 3 70 theme non-reductive 599:611 arg1 β-elimination 613:625 non-reductive β-elimination 599:625 non-reductive β-elimination in the presence of hydroxylamine 599:658 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 5 71 theme mass 1112:1115 arg1 spectrometry 1117:1128 mass spectrometry 1112:1128 mass spectrometry 1112:1128 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. 36877384 7 72 theme O-glycans 1445:1453 arg1 characterization 1385:1400 detailed characterization 1376:1400 detailed characterization of biologically relevant sialylated N- and O-glycans 1376:1453 This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins. 36877384 3 73 theme linkage-specific 490:505 arg1 analysis 523:530 sialic acid linkage-specific O-linked glycan analysis 478:530 sialic acid linkage-specific O-linked glycan analysis 478:530 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 5 74 theme ethyl-esterified 1004:1019 arg1 O-glycans 1021:1029 ethyl-esterified O-glycans 1004:1029 ethyl-esterified O-glycans 1004:1029 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. 36877384 5 75 theme glycan 1075:1080 arg1 isomers 1082:1088 the resulting sialylated glycan isomers 1050:1088 the resulting sialylated glycan isomers 1050:1088 In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. 36877384 6 76 theme glycan 1263:1268 arg1 analyses 1270:1277 simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses 1186:1277 simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein 1186:1301 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 6 77 theme quantitative 1200:1211 arg1 N- 1247:1248 simultaneous, quantitative, and sialic acid linkage-specific N- 1186:1248 simultaneous, quantitative, and sialic acid linkage-specific N- 1186:1248 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 0 78 theme glycan 62:67 arg1 analysis 69:76 glycan analysis 62:76 glycan analysis 62:76 Simultaneous and sialic acid linkage-specific N- and O-linked glycan analysis by ester-to-amide derivatization. 36877384 1 79 attach linked 142:147 arg2 O-glycans 132:140 O-glycans 132:140 O-glycans linked to serine or threonine residues in glycoproteins 132:196 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 1 79 attach linked 142:147 arg1 serine 152:157 serine 152:157 serine 152:157 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 1 79 attach linked 142:147 arg1 threonine 162:170 threonine 162:170 threonine 162:170 Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. 36877384 6 80 gly glycoprotein 1290:1301 arg1 glycoprotein 1290:1301 a model glycoprotein 1282:1301 a model glycoprotein 1282:1301 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36877384 4 81 from solid-phase 931:941 arg1 groups 897:902 methyl or ethyl ester groups 875:902 methyl or ethyl ester groups of sialic acid residues on solid-phase 875:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 4 81 from solid-phase 931:941 arg1 residues 919:926 sialic acid residues 907:926 sialic acid residues on solid-phase 907:941 O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. 36877384 2 82 theme various 411:417 arg1 linkages 419:426 various linkages 411:426 various linkages 411:426 Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. 36877384 3 83 from β-elimination 613:625 arg1 presence 634:641 the presence 630:641 the presence of hydroxylamine 630:658 In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. 36877384 6 84 theme acid 1225:1228 arg1 N- 1247:1248 simultaneous, quantitative, and sialic acid linkage-specific N- 1186:1248 simultaneous, quantitative, and sialic acid linkage-specific N- 1186:1248 In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. 36619451 6 0 theme mg 1164:1165 arg1 DW 1171:1172 9.50 ± 0.50 mg g-1 DW 1152:1172 9.50 ± 0.50 mg g-1 DW 1152:1172 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 6 0 theme mg 1164:1165 arg1 C. officinalis 1136:1149 C. officinalis 1136:1149 C. officinalis (9.50 ± 0.50 mg g-1 DW) 1136:1173 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 2 1 theme hydrophilic 495:505 arg1 nature 507:512 the hydrophilic nature 491:512 the hydrophilic nature of polysaccharides 491:531 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 8 2 theme electron 1351:1358 arg1 SEM 1372:1374 SEM 1372:1374 SEM 1372:1374 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 8 2 theme electron 1351:1358 arg1 microscopy 1360:1369 Scanning electron microscopy 1342:1369 Scanning electron microscopy (SEM) 1342:1375 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 2 3 theme swelling 542:549 arg1 SWC 567:569 SWC 567:569 SWC 567:569 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 3 theme swelling 542:549 arg1 capacity 557:564 swelling water capacity 542:564 swelling water capacity (SWC) 542:570 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 4 4 theme & 904:904 arg1 DW 929:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 2 5 theme 1.619 396:400 arg1 DW 436:437 3.1 ± 0.50 g g-1 DW 419:437 3.1 ± 0.50 g g-1 DW 419:437 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 5 theme 1.619 396:400 arg1 DW 415:416 1.619 ± 0.08 g g-1 DW 396:416 1.619 ± 0.08 g g-1 DW 396:416 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 10 6 contain possesses 1592:1600 arg1 A.rigida 1583:1590 A.rigida 1583:1590 A.rigida 1583:1590 From GC-MS data A.rigida possesses 16 bioactive components with biological properties. 36619451 10 6 contain possesses 1592:1600 arg2 components 1615:1624 16 bioactive components 1602:1624 16 bioactive components with biological properties 1602:1651 From GC-MS data A.rigida possesses 16 bioactive components with biological properties. 36619451 4 7 theme ± 913:913 arg1 DW 929:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 11 8 theme functional 1729:1738 arg1 foods 1740:1744 functional foods 1729:1744 functional foods 1729:1744 As a result, J. rubens and A. rigida could be employed as an ingredient in functional foods and drug manufacture. 36619451 3 9 dep % 771:771 arg1 ± 765:765 ± 765:765 ± 765:765 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 11 10 theme drug 1750:1753 arg1 manufacture 1755:1765 drug manufacture 1750:1765 drug manufacture 1750:1765 As a result, J. rubens and A. rigida could be employed as an ingredient in functional foods and drug manufacture. 36619451 8 11 theme X-ray 1399:1403 arg1 EDX 1419:1421 EDX 1419:1421 EDX 1419:1421 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 8 11 theme X-ray 1399:1403 arg1 spectroscopy 1405:1416 Energy dispersive X-ray spectroscopy 1381:1416 Energy dispersive X-ray spectroscopy (EDX) 1381:1422 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 4 12 theme mg 897:898 arg1 DW 929:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 3 13 theme carbohydrates 639:651 arg1 value 630:634 A higher value 621:634 A higher value of carbohydrates (49.88 ± 2.56% DW) 621:670 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 9 14 theme disulfides 1504:1513 arg1 group 1515:1519 disulfides group 1504:1519 disulfides group 1504:1519 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 5 15 dep globulin 973:980 arg1 DW 1041:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 5 16 theme & 1019:1019 arg1 DW 1041:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 3 17 theme 2.56 662:665 arg1 carbohydrates 639:651 carbohydrates 639:651 carbohydrates (49.88 ± 2.56% DW) 639:670 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 3 17 theme 2.56 662:665 arg1 DW 668:669 49.88 ± 2.56% DW 654:669 49.88 ± 2.56% DW 654:669 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 9 18 theme infrared 1448:1455 arg1 spectroscopy 1464:1475 infrared (FTIR) spectroscopy 1448:1475 infrared (FTIR) spectroscopy 1448:1475 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 4 19 theme mg 922:923 arg1 DW 929:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 5 20 theme ± 1027:1027 arg1 DW 1041:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 6 21 theme insoluble 1097:1105 arg1 fraction 1115:1122 insoluble protein fraction 1097:1122 insoluble protein fraction 1097:1122 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 9 22 theme group 1515:1519 arg1 peak 1496:1499 the S-S stretching peak 1477:1499 the S-S stretching peak of disulfides group at 462 cm-1 1477:1531 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 9 22 theme group 1515:1519 arg1 fingerprint 1541:1551 the fingerprint 1537:1551 the fingerprint of J. rubens 1537:1564 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 1 23 from difference 155:164 arg1 properties 185:194 physicochemical properties 169:194 physicochemical properties 169:194 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 23 from difference 155:164 arg1 compositions 214:225 the proximate compositions 200:225 the proximate compositions 200:225 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 5 24 theme 1.90 1004:1007 arg1 ± 1002:1002 ± 1002:1002 ± 1002:1002 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 5 25 theme g-1 1012:1014 arg1 DW 1041:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 2 26 theme DW 616:617 arg1 g-1 612:614 5.25 ± 0.38 mL g-1 DW 597:617 5.25 ± 0.38 mL g-1 DW 597:617 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 3 27 theme % 734:734 arg1 protein 713:719 protein (36.99 ± 1.36% DW) and lipid contents 713:757 protein 713:719 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 3 27 theme % 734:734 arg1 DW 736:737 36.99 ± 1.36% DW 722:737 36.99 ± 1.36% DW 722:737 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 2 28 theme g-1 432:434 arg1 DW 436:437 3.1 ± 0.50 g g-1 DW 419:437 3.1 ± 0.50 g g-1 DW 419:437 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 28 theme g-1 432:434 arg1 DW 415:416 1.619 ± 0.08 g g-1 DW 396:416 1.619 ± 0.08 g g-1 DW 396:416 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 29 theme water 551:555 arg1 SWC 567:569 SWC 567:569 SWC 567:569 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 29 theme water 551:555 arg1 capacity 557:564 swelling water capacity 542:564 swelling water capacity (SWC) 542:570 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 30 theme oil 368:370 arg1 capacity 380:387 oil holding capacity 368:387 oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) 368:452 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 30 theme oil 368:370 arg1 OHC 390:392 OHC 390:392 OHC 390:392 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 3 31 theme ± 728:728 arg1 protein 713:719 protein (36.99 ± 1.36% DW) and lipid contents 713:757 protein 713:719 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 3 31 theme ± 728:728 arg1 DW 736:737 36.99 ± 1.36% DW 722:737 36.99 ± 1.36% DW 722:737 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 2 32 theme ± 402:402 arg1 DW 436:437 3.1 ± 0.50 g g-1 DW 419:437 3.1 ± 0.50 g g-1 DW 419:437 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 32 theme ± 402:402 arg1 DW 415:416 1.619 ± 0.08 g g-1 DW 396:416 1.619 ± 0.08 g g-1 DW 396:416 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 0 33 theme Physico-chemodiversity 0:21 arg1 variation 23:31 Physico-chemodiversity variation 0:31 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 0:114 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 11 34 from ingredient 1715:1724 arg1 foods 1740:1744 functional foods 1729:1744 functional foods 1729:1744 As a result, J. rubens and A. rigida could be employed as an ingredient in functional foods and drug manufacture. 36619451 11 34 from ingredient 1715:1724 arg1 manufacture 1755:1765 drug manufacture 1750:1765 drug manufacture 1750:1765 As a result, J. rubens and A. rigida could be employed as an ingredient in functional foods and drug manufacture. 36619451 4 35 dep specimens 873:881 arg1 ± 890:890 ± 890:890 ± 890:890 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 0 36 dep Eastern 81:87 arg1 Harbor 89:94 Harbor 89:94 Harbor 89:94 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 3 37 theme lipid 744:748 arg1 contents 750:757 protein (36.99 ± 1.36% DW) and lipid contents 713:757 contents 750:757 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 4 38 theme protein 830:836 arg1 fractions 838:846 Albumin and protamine protein fractions 808:846 Albumin and protamine protein fractions 808:846 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 2 39 dep recorded 335:342 arg1 whereas 534:540 whereas 534:540 whereas 534:540 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 5 40 theme mg 1034:1035 arg1 DW 1041:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 7 41 theme photosynthetic 1232:1245 arg1 pigments 1247:1254 the photosynthetic pigments 1228:1254 the photosynthetic pigments 1228:1254 J. rubens specimens were recorded maximum values of the photosynthetic pigments. 36619451 10 42 with components 1615:1624 arg1 properties 1642:1651 biological properties 1631:1651 biological properties 1631:1651 From GC-MS data A.rigida possesses 16 bioactive components with biological properties. 36619451 8 43 theme different 1261:1269 arg1 types 1279:1283 The different surface types 1257:1283 The different surface types 1257:1283 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 2 44 dep capacity 380:387 arg1 DW 436:437 3.1 ± 0.50 g g-1 DW 419:437 3.1 ± 0.50 g g-1 DW 419:437 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 44 dep capacity 380:387 arg1 DW 415:416 1.619 ± 0.08 g g-1 DW 396:416 1.619 ± 0.08 g g-1 DW 396:416 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 45 theme g 409:409 arg1 DW 436:437 3.1 ± 0.50 g g-1 DW 419:437 3.1 ± 0.50 g g-1 DW 419:437 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 45 theme g 409:409 arg1 DW 415:416 1.619 ± 0.08 g g-1 DW 396:416 1.619 ± 0.08 g g-1 DW 396:416 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 0 46 theme calcareous 57:66 arg1 Eastern 81:87 Eastern 81:87 Eastern 81:87 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 0 46 theme calcareous 57:66 arg1 Alexandria 97:106 Alexandria 97:106 Alexandria 97:106 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 0 46 theme calcareous 57:66 arg1 seaweed 72:78 the most common calcareous red seaweed 41:78 the most common calcareous red seaweed 41:78 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 0 46 theme calcareous 57:66 arg1 Egypt 109:113 Egypt 109:113 Egypt 109:113 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 7 47 theme maximum 1210:1216 arg1 values 1218:1223 maximum values 1210:1223 maximum values of the photosynthetic pigments 1210:1254 J. rubens specimens were recorded maximum values of the photosynthetic pigments. 36619451 8 48 theme elemental 1289:1297 arg1 analysis 1299:1306 elemental analysis 1289:1306 elemental analysis of three species 1289:1323 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 10 49 theme GC-MS 1572:1576 arg1 data 1578:1581 GC-MS data 1572:1581 GC-MS data 1572:1581 From GC-MS data A.rigida possesses 16 bioactive components with biological properties. 36619451 9 50 theme stretching 1485:1494 arg1 peak 1496:1499 the S-S stretching peak 1477:1499 the S-S stretching peak of disulfides group at 462 cm-1 1477:1531 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 9 50 theme stretching 1485:1494 arg1 fingerprint 1541:1551 the fingerprint 1537:1551 the fingerprint of J. rubens 1537:1564 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 1 51 theme calcareous 237:246 arg1 rubens 291:296 rubens 291:296 rubens 291:296 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 51 theme calcareous 237:246 arg1 rigida 312:317 rigida 312:317 rigida 312:317 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 51 theme calcareous 237:246 arg1 Corallina 262:270 Corallina 262:270 Corallina 262:270 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 51 theme calcareous 237:246 arg1 seaweeds 252:259 common calcareous red seaweeds 230:259 common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida" 230:318 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 7 52 theme J. rubens 1176:1184 arg1 specimens 1186:1194 J. rubens specimens 1176:1194 J. rubens specimens 1176:1194 J. rubens specimens were recorded maximum values of the photosynthetic pigments. 36619451 8 53 theme species 1317:1323 arg1 types 1279:1283 The different surface types 1257:1283 The different surface types 1257:1283 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 8 53 theme species 1317:1323 arg1 analysis 1299:1306 elemental analysis 1289:1306 elemental analysis of three species 1289:1323 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 3 54 located observed 676:683 arg1 Contrariwise 699:710 Contrariwise 699:710 Contrariwise 699:710 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 3 54 located observed 676:683 arg2 value 630:634 A higher value 621:634 A higher value of carbohydrates (49.88 ± 2.56% DW) 621:670 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 6 55 theme g-1 1167:1169 arg1 DW 1171:1172 9.50 ± 0.50 mg g-1 DW 1152:1172 9.50 ± 0.50 mg g-1 DW 1152:1172 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 6 55 theme g-1 1167:1169 arg1 C. officinalis 1136:1149 C. officinalis 1136:1149 C. officinalis (9.50 ± 0.50 mg g-1 DW) 1136:1173 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 1 56 theme seaweeds 252:259 arg1 properties 185:194 physicochemical properties 169:194 physicochemical properties 169:194 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 56 theme seaweeds 252:259 arg1 compositions 214:225 the proximate compositions 200:225 the proximate compositions 200:225 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 8 57 theme dispersive 1388:1397 arg1 EDX 1419:1421 EDX 1419:1421 EDX 1419:1421 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 8 57 theme dispersive 1388:1397 arg1 spectroscopy 1405:1416 Energy dispersive X-ray spectroscopy 1381:1416 Energy dispersive X-ray spectroscopy (EDX) 1381:1422 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 8 58 theme Scanning 1342:1349 arg1 SEM 1372:1374 SEM 1372:1374 SEM 1372:1374 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 8 58 theme Scanning 1342:1349 arg1 microscopy 1360:1369 Scanning electron microscopy 1342:1369 Scanning electron microscopy (SEM) 1342:1375 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 10 59 theme biological 1631:1640 arg1 properties 1642:1651 biological properties 1631:1651 biological properties 1631:1651 From GC-MS data A.rigida possesses 16 bioactive components with biological properties. 36619451 5 60 dep mg 1009:1010 arg1 ± 1002:1002 ± 1002:1002 ± 1002:1002 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 1 61 theme physicochemical 169:183 arg1 properties 185:194 physicochemical properties 169:194 physicochemical properties 169:194 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 2 62 theme polysaccharides 517:531 arg1 nature 507:512 the hydrophilic nature 491:512 the hydrophilic nature of polysaccharides 491:531 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 4 63 theme 2.29 892:895 arg1 mg 897:898 mg 897:898 mg 897:898 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 3 64 theme higher 623:628 arg1 value 630:634 A higher value 621:634 A higher value of carbohydrates (49.88 ± 2.56% DW) 621:670 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 3 65 dep DW 773:774 arg1 % 771:771 % 771:771 % 771:771 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 4 66 theme g-1 900:902 arg1 DW 929:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 9 67 dep infrared 1448:1455 arg1 FTIR 1458:1461 FTIR 1458:1461 FTIR 1458:1461 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 6 68 from C. officinalis 1136:1149 arg1 high 1128:1131 high 1128:1131 high 1128:1131 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 1 69 theme proximate 204:212 arg1 compositions 214:225 the proximate compositions 200:225 the proximate compositions 200:225 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 2 70 theme ± 602:602 arg1 g-1 612:614 5.25 ± 0.38 mL g-1 DW 597:617 5.25 ± 0.38 mL g-1 DW 597:617 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 1 71 dep Corallina 262:270 arg1 officinalis 272:282 officinalis 272:282 Corallina officinalis 262:282 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 4 72 theme other 952:956 arg1 species 958:964 other species 952:964 other species 952:964 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 5 73 theme DW 1016:1017 arg1 DW 1041:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 1 74 theme present 120:126 arg1 study 128:132 The present study 116:132 The present study 116:132 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 9 75 from fourier 1430:1436 arg1 peak 1496:1499 the S-S stretching peak 1477:1499 the S-S stretching peak of disulfides group at 462 cm-1 1477:1531 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 9 75 from fourier 1430:1436 arg1 fingerprint 1541:1551 the fingerprint 1537:1551 the fingerprint of J. rubens 1537:1564 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 2 76 theme other 465:469 arg1 species 471:477 those other species 459:477 those other species relating to the hydrophilic nature of polysaccharides 459:531 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 1 77 dep seaweeds 252:259 arg1 rubens 291:296 rubens 291:296 rubens 291:296 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 77 dep seaweeds 252:259 arg1 rigida 312:317 rigida 312:317 rigida 312:317 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 77 dep seaweeds 252:259 arg1 Corallina 262:270 Corallina 262:270 Corallina 262:270 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 77 dep seaweeds 252:259 arg1 seaweeds 252:259 common calcareous red seaweeds 230:259 common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida" 230:318 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 4 78 theme g-1 925:927 arg1 DW 929:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW 892:930 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 3 79 theme % 666:666 arg1 carbohydrates 639:651 carbohydrates 639:651 carbohydrates (49.88 ± 2.56% DW) 639:670 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 3 79 theme % 666:666 arg1 DW 668:669 49.88 ± 2.56% DW 654:669 49.88 ± 2.56% DW 654:669 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 6 80 theme protein 1107:1113 arg1 fraction 1115:1122 insoluble protein fraction 1097:1122 insoluble protein fraction 1097:1122 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 6 81 from high 1128:1131 arg1 DW 1171:1172 9.50 ± 0.50 mg g-1 DW 1152:1172 9.50 ± 0.50 mg g-1 DW 1152:1172 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 6 81 from high 1128:1131 arg1 C. officinalis 1136:1149 C. officinalis 1136:1149 C. officinalis (9.50 ± 0.50 mg g-1 DW) 1136:1173 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 2 82 dep higher 576:581 arg1 g-1 612:614 5.25 ± 0.38 mL g-1 DW 597:617 5.25 ± 0.38 mL g-1 DW 597:617 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 83 theme ± 423:423 arg1 g-1 432:434 3.1 ± 0.50 g g-1 419:434 3.1 ± 0.50 g g-1 DW 419:437 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 84 theme mL 609:610 arg1 g-1 612:614 5.25 ± 0.38 mL g-1 DW 597:617 5.25 ± 0.38 mL g-1 DW 597:617 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 3 85 theme ± 660:660 arg1 carbohydrates 639:651 carbohydrates 639:651 carbohydrates (49.88 ± 2.56% DW) 639:670 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 3 85 theme ± 660:660 arg1 DW 668:669 49.88 ± 2.56% DW 654:669 49.88 ± 2.56% DW 654:669 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 9 86 dep fourier 1430:1436 arg1 transform 1438:1446 transform 1438:1446 transform infrared (FTIR) spectroscopy 1438:1475 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 5 87 from A. rigida 1072:1080 arg1 high 1064:1067 high 1064:1067 high 1064:1067 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 2 88 theme g 430:430 arg1 g-1 432:434 3.1 ± 0.50 g g-1 419:434 3.1 ± 0.50 g g-1 DW 419:437 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 9 89 theme S-S 1481:1483 arg1 peak 1496:1499 the S-S stretching peak 1477:1499 the S-S stretching peak of disulfides group at 462 cm-1 1477:1531 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 9 89 theme S-S 1481:1483 arg1 fingerprint 1541:1551 the fingerprint 1537:1551 the fingerprint of J. rubens 1537:1564 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 6 90 theme ± 1157:1157 arg1 DW 1171:1172 9.50 ± 0.50 mg g-1 DW 1152:1172 9.50 ± 0.50 mg g-1 DW 1152:1172 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 6 90 theme ± 1157:1157 arg1 C. officinalis 1136:1149 C. officinalis 1136:1149 C. officinalis (9.50 ± 0.50 mg g-1 DW) 1136:1173 Contrariwise, insoluble protein fraction was high in C. officinalis (9.50 ± 0.50 mg g-1 DW). 36619451 3 91 theme 1.36 730:733 arg1 protein 713:719 protein (36.99 ± 1.36% DW) and lipid contents 713:757 protein 713:719 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 3 91 theme 1.36 730:733 arg1 DW 736:737 36.99 ± 1.36% DW 722:737 36.99 ± 1.36% DW 722:737 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 5 92 from high 1064:1067 arg1 A. rigida 1072:1080 A. rigida 1072:1080 A. rigida 1072:1080 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 4 93 theme Albumin 808:814 arg1 fractions 838:846 Albumin and protamine protein fractions 808:846 Albumin and protamine protein fractions 808:846 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 5 94 theme 2.20 1029:1032 arg1 DW 1041:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 4 95 theme protamine 820:828 arg1 fractions 838:846 Albumin and protamine protein fractions 808:846 Albumin and protamine protein fractions 808:846 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 8 96 theme surface 1271:1277 arg1 types 1279:1283 The different surface types 1257:1283 The different surface types 1257:1283 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 5 97 theme g-1 1037:1039 arg1 DW 1041:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW 996:1042 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 0 98 theme common 50:55 arg1 Eastern 81:87 Eastern 81:87 Eastern 81:87 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 0 98 theme common 50:55 arg1 Alexandria 97:106 Alexandria 97:106 Alexandria 97:106 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 0 98 theme common 50:55 arg1 seaweed 72:78 the most common calcareous red seaweed 41:78 the most common calcareous red seaweed 41:78 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 0 98 theme common 50:55 arg1 Egypt 109:113 Egypt 109:113 Egypt 109:113 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 7 99 theme pigments 1247:1254 arg1 values 1218:1223 maximum values 1210:1223 maximum values of the photosynthetic pigments 1210:1254 J. rubens specimens were recorded maximum values of the photosynthetic pigments. 36619451 2 100 theme g-1 411:413 arg1 DW 436:437 3.1 ± 0.50 g g-1 DW 419:437 3.1 ± 0.50 g g-1 DW 419:437 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 100 theme g-1 411:413 arg1 DW 415:416 1.619 ± 0.08 g g-1 DW 396:416 1.619 ± 0.08 g g-1 DW 396:416 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 101 theme holding 372:378 arg1 capacity 380:387 oil holding capacity 368:387 oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) 368:452 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 2 101 theme holding 372:378 arg1 OHC 390:392 OHC 390:392 OHC 390:392 J. rubens was recorded highly water (WHC), and oil holding capacity (OHC) (1.619 ± 0.08 g g-1 DW, 3.1 ± 0.50 g g-1 DW, respectively) than those other species relating to the hydrophilic nature of polysaccharides, whereas swelling water capacity (SWC) was higher in A. rigida (5.25 ± 0.38 mL g-1 DW). 36619451 0 102 theme red 68:70 arg1 Eastern 81:87 Eastern 81:87 Eastern 81:87 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 0 102 theme red 68:70 arg1 Alexandria 97:106 Alexandria 97:106 Alexandria 97:106 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 0 102 theme red 68:70 arg1 seaweed 72:78 the most common calcareous red seaweed 41:78 the most common calcareous red seaweed 41:78 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 0 102 theme red 68:70 arg1 Egypt 109:113 Egypt 109:113 Egypt 109:113 Physico-chemodiversity variation between the most common calcareous red seaweed, Eastern Harbor, Alexandria, Egypt. 36619451 3 103 theme 0.49 767:770 arg1 ± 765:765 ± 765:765 ± 765:765 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 9 104 from cm-1 1528:1531 arg1 peak 1496:1499 the S-S stretching peak 1477:1499 the S-S stretching peak of disulfides group at 462 cm-1 1477:1531 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 9 104 from cm-1 1528:1531 arg1 fingerprint 1541:1551 the fingerprint 1537:1551 the fingerprint of J. rubens 1537:1564 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 3 105 theme 5.85 760:763 arg1 ± 765:765 ± 765:765 ± 765:765 A higher value of carbohydrates (49.88 ± 2.56% DW) was observed in J. rubens, Contrariwise, protein (36.99 ± 1.36% DW) and lipid contents (5.85 ± 0.49% DW) were higher in C. officinalis. 36619451 4 106 theme J. rubens 863:871 arg1 specimens 873:881 J. rubens specimens 863:881 J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) 863:945 Albumin and protamine protein fractions were higher in J. rubens specimens (45.11 ± 2.29 mg g-1 & 0.0014 ± 0.0007 mg g-1 DW, respectively) than other species. 36619451 1 107 theme common 230:235 arg1 rubens 291:296 rubens 291:296 rubens 291:296 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 107 theme common 230:235 arg1 rigida 312:317 rigida 312:317 rigida 312:317 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 107 theme common 230:235 arg1 Corallina 262:270 Corallina 262:270 Corallina 262:270 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 107 theme common 230:235 arg1 seaweeds 252:259 common calcareous red seaweeds 230:259 common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida" 230:318 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 5 108 dep DW 1041:1042 arg1 mg 1009:1010 mg 1009:1010 mg 1009:1010 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 36619451 9 109 theme J. rubens 1556:1564 arg1 peak 1496:1499 the S-S stretching peak 1477:1499 the S-S stretching peak of disulfides group at 462 cm-1 1477:1531 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 9 109 theme J. rubens 1556:1564 arg1 fingerprint 1541:1551 the fingerprint 1537:1551 the fingerprint of J. rubens 1537:1564 From fourier transform infrared (FTIR) spectroscopy the S-S stretching peak of disulfides group at 462 cm-1 was the fingerprint of J. rubens. 36619451 10 110 theme bioactive 1605:1613 arg1 components 1615:1624 16 bioactive components 1602:1624 16 bioactive components with biological properties 1602:1651 From GC-MS data A.rigida possesses 16 bioactive components with biological properties. 36619451 1 111 theme red 248:250 arg1 rubens 291:296 rubens 291:296 rubens 291:296 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 111 theme red 248:250 arg1 rigida 312:317 rigida 312:317 rigida 312:317 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 111 theme red 248:250 arg1 Corallina 262:270 Corallina 262:270 Corallina 262:270 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 1 111 theme red 248:250 arg1 seaweeds 252:259 common calcareous red seaweeds 230:259 common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida" 230:318 The present study sought to detect the difference in physicochemical properties and the proximate compositions of common calcareous red seaweeds "Corallina officinalis, Jania rubens, and Amphiroa rigida". 36619451 8 112 theme Energy 1381:1386 arg1 EDX 1419:1421 EDX 1419:1421 EDX 1419:1421 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 8 112 theme Energy 1381:1386 arg1 spectroscopy 1405:1416 Energy dispersive X-ray spectroscopy 1381:1416 Energy dispersive X-ray spectroscopy (EDX) 1381:1422 The different surface types and elemental analysis of three species were examined by Scanning electron microscopy (SEM) and Energy dispersive X-ray spectroscopy (EDX). 36619451 5 113 theme 31.70 996:1000 arg1 ± 1002:1002 ± 1002:1002 ± 1002:1002 While globulin and glutilin (31.70 ± 1.90 mg g-1 DW & 41.93 ± 2.20 mg g-1 DW, respectively) were high in A. rigida. 35726352 10 0 dep CONCLUSION 1399:1408 arg1 realised 1433:1440 realised 1433:1440 realised 1433:1440 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 5 1 from AR 788:789 arg1 components 733:742 the main components 724:742 the main components of flavonoids, saponins, and amino acids in AR 724:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 10 2 theme compounds 1530:1538 arg1 identification 1475:1488 identification 1475:1488 identification 1475:1488 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 10 2 theme compounds 1530:1538 arg1 classification 1456:1469 efficient classification 1446:1469 efficient classification 1446:1469 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 8 3 theme neutral 1184:1190 arg1 losses 1192:1197 neutral losses 1184:1197 neutral losses (NLs) 1184:1203 Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. 35726352 8 3 theme neutral 1184:1190 arg1 NLs 1200:1202 NLs 1200:1202 NLs 1200:1202 Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. 35726352 10 4 theme saponins 1505:1512 arg1 identification 1475:1488 identification 1475:1488 identification 1475:1488 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 10 4 theme saponins 1505:1512 arg1 classification 1456:1469 efficient classification 1446:1469 efficient classification 1446:1469 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 1 5 theme antioxidant 261:271 arg1 activities 273:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 4 6 from identification 594:607 arg1 AR 641:642 AR 641:642 AR 641:642 Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. 35726352 5 7 theme amino 773:777 arg1 acids 779:783 amino acids 773:783 amino acids in AR 773:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 1 8 theme various 171:177 arg1 activities 273:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 1 8 theme various 171:177 arg1 bioactivities 179:191 various bioactivities 171:191 various bioactivities 171:191 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 6 9 theme quadrupole 891:900 arg1 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 6 9 theme quadrupole 891:900 arg1 spectrometry 907:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry 831:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) 831:934 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 5 10 theme main 728:731 arg1 components 733:742 the main components 724:742 the main components of flavonoids, saponins, and amino acids in AR 724:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 5 11 from acids 779:783 arg1 AR 788:789 AR 788:789 AR 788:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 2 12 theme amino 307:311 arg1 saponins 297:304 saponins 297:304 saponins 297:304 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 12 theme amino 307:311 arg1 polysaccharides 324:338 polysaccharides 324:338 polysaccharides 324:338 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 12 theme amino 307:311 arg1 components 360:369 the main active components 344:369 the main active components in AR 344:375 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 12 theme amino 307:311 arg1 acids 313:317 amino acids 307:317 amino acids 307:317 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 12 theme amino 307:311 arg1 Flavonoids 285:294 Flavonoids 285:294 Flavonoids 285:294 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 9 13 theme amino 1386:1390 arg1 acids 1392:1396 10 amino acids 1383:1396 10 amino acids 1383:1396 RESULTS A total of 45 chemical constituents were successfully screened out, including 22 flavonoids, 13 saponins, and 10 amino acids. 35726352 4 14 from classification 575:588 arg1 AR 641:642 AR 641:642 AR 641:642 Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. 35726352 4 15 theme constituents 625:636 arg1 classification 575:588 rapid classification 569:588 rapid classification 569:588 Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. 35726352 4 15 theme constituents 625:636 arg1 identification 594:607 identification 594:607 identification 594:607 Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. 35726352 10 16 theme efficient 1446:1454 arg1 classification 1456:1469 efficient classification 1446:1469 efficient classification 1446:1469 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 7 17 theme fragmentation 982:994 arg1 information 996:1006 fragmentation information 982:1006 fragmentation information 982:1006 Firstly, fragmentation information was obtained in the positive and negative ion modes. 35726352 10 18 theme further 1574:1580 arg1 study 1582:1586 further study 1574:1586 further study on AR 1574:1592 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 1 19 contain has 167:169 arg1 Astragalus 151:160 Astragalus 151:160 Astragalus (AR) 151:165 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 1 19 contain has 167:169 arg2 bioactivities 179:191 various bioactivities 171:191 various bioactivities 171:191 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 1 19 contain has 167:169 arg2 activities 273:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 1 19 contain has 167:169 arg1 AR 163:164 AR 163:164 AR 163:164 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 8 20 theme rapid 1082:1086 arg1 classification 1088:1101 rapid classification 1082:1101 rapid classification 1082:1101 Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. 35726352 3 21 theme Chinese 484:490 arg1 TCM 502:504 TCM 502:504 TCM 502:504 However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). 35726352 3 21 theme Chinese 484:490 arg1 medicine 492:499 this traditional Chinese medicine 467:499 this traditional Chinese medicine (TCM) 467:505 However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). 35726352 9 22 theme chemical 1287:1294 arg1 constituents 1296:1307 45 chemical constituents 1284:1307 45 chemical constituents 1284:1307 RESULTS A total of 45 chemical constituents were successfully screened out, including 22 flavonoids, 13 saponins, and 10 amino acids. 35726352 5 23 theme flavonoids 747:756 arg1 components 733:742 the main components 724:742 the main components of flavonoids, saponins, and amino acids in AR 724:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 4 24 theme rapid 569:573 arg1 classification 575:588 rapid classification 569:588 rapid classification 569:588 Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. 35726352 6 25 theme liquid 854:859 arg1 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 6 25 theme liquid 854:859 arg1 spectrometry 907:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry 831:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) 831:934 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 0 26 theme Rapid 0:4 arg1 classification 6:19 Rapid classification 0:19 Rapid classification 0:19 Rapid classification and identification of chemical components of Astragali radix by UPLC-Q-TOF-MS. 35726352 6 27 theme mass 902:905 arg1 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 6 27 theme mass 902:905 arg1 spectrometry 907:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry 831:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) 831:934 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 10 28 theme flavonoids 1493:1502 arg1 identification 1475:1488 identification 1475:1488 identification 1475:1488 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 10 28 theme flavonoids 1493:1502 arg1 classification 1456:1469 efficient classification 1446:1469 efficient classification 1446:1469 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 2 29 from components 360:369 arg1 AR 374:375 AR 374:375 AR 374:375 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 3 30 theme complex 391:397 arg1 compositions 408:419 its complex chemical compositions 387:419 its complex chemical compositions 387:419 However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). 35726352 10 31 from classification 1456:1469 arg1 AR 1543:1544 AR 1543:1544 AR 1543:1544 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 8 32 dep classification 1088:1101 arg1 the 1078:1080 the 1078:1080 the 1078:1080 Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. 35726352 1 33 theme INTRODUCTION 100:111 arg1 studies 129:135 INTRODUCTION Pharmacological studies 100:135 INTRODUCTION Pharmacological studies 100:135 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 6 34 dep METHODS 792:798 arg1 analysed 817:824 analysed 817:824 were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques 812:970 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 1 35 theme anticancer 204:213 arg1 activities 273:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 9 36 dep screened 1327:1334 arg1 out 1336:1338 out 1336:1338 out 1336:1338 RESULTS A total of 45 chemical constituents were successfully screened out, including 22 flavonoids, 13 saponins, and 10 amino acids. 35726352 10 37 theme acid 1525:1528 arg1 compounds 1530:1538 amino acid compounds 1519:1538 amino acid compounds 1519:1538 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 10 38 theme established 1414:1424 arg1 method 1426:1431 The established method 1410:1431 The established method 1410:1431 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 1 39 theme Pharmacological 113:127 arg1 studies 129:135 INTRODUCTION Pharmacological studies 100:135 INTRODUCTION Pharmacological studies 100:135 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 4 40 from AR 641:642 arg1 classification 575:588 rapid classification 569:588 rapid classification 569:588 Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. 35726352 4 40 from AR 641:642 arg1 identification 594:607 identification 594:607 identification 594:607 Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. 35726352 3 41 theme traditional 472:482 arg1 TCM 502:504 TCM 502:504 TCM 502:504 However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). 35726352 3 41 theme traditional 472:482 arg1 medicine 492:499 this traditional Chinese medicine 467:499 this traditional Chinese medicine (TCM) 467:505 However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). 35726352 10 42 dep classification 1456:1469 arg1 the 1442:1444 the 1442:1444 the 1442:1444 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 10 43 from identification 1475:1488 arg1 AR 1543:1544 AR 1543:1544 AR 1543:1544 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 10 44 theme amino 1519:1523 arg1 compounds 1530:1538 amino acid compounds 1519:1538 amino acid compounds 1519:1538 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 5 45 from components 733:742 arg1 AR 788:789 AR 788:789 AR 788:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 6 46 theme data 940:943 arg1 techniques 961:970 data post-processing techniques 940:970 data post-processing techniques 940:970 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 1 47 theme antiaging 216:224 arg1 activities 273:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 0 48 theme chemical 43:50 arg1 components 52:61 chemical components 43:61 chemical components of Astragali radix 43:80 Rapid classification and identification of chemical components of Astragali radix by UPLC-Q-TOF-MS. 35726352 8 49 theme components 1128:1137 arg1 identification 1107:1120 identification 1107:1120 identification 1107:1120 Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. 35726352 8 49 theme components 1128:1137 arg1 classification 1088:1101 rapid classification 1082:1101 rapid classification 1082:1101 Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. 35726352 5 50 from flavonoids 747:756 arg1 AR 788:789 AR 788:789 AR 788:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 10 51 from study 1582:1586 arg1 AR 1591:1592 AR 1591:1592 AR 1591:1592 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 4 52 from constituents 625:636 arg1 AR 641:642 AR 641:642 AR 641:642 Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. 35726352 3 53 theme certain 427:433 arg1 difficulties 435:446 certain difficulties 427:446 certain difficulties 427:446 However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). 35726352 5 54 theme acids 779:783 arg1 components 733:742 the main components 724:742 the main components of flavonoids, saponins, and amino acids in AR 724:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 6 55 theme chromatography 861:874 arg1 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 6 55 theme chromatography 861:874 arg1 spectrometry 907:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry 831:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) 831:934 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 1 56 theme anti-inflammatory 227:243 arg1 activities 273:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 3 57 theme chemical 399:406 arg1 compositions 408:419 its complex chemical compositions 387:419 its complex chemical compositions 387:419 However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). 35726352 5 58 theme saponins 759:766 arg1 components 733:742 the main components 724:742 the main components of flavonoids, saponins, and amino acids in AR 724:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 2 59 theme active 353:358 arg1 acids 313:317 amino acids 307:317 amino acids 307:317 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 59 theme active 353:358 arg1 polysaccharides 324:338 polysaccharides 324:338 polysaccharides 324:338 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 59 theme active 353:358 arg1 saponins 297:304 saponins 297:304 saponins 297:304 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 59 theme active 353:358 arg1 components 360:369 the main active components 344:369 the main active components in AR 344:375 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 59 theme active 353:358 arg1 Flavonoids 285:294 Flavonoids 285:294 Flavonoids 285:294 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 0 60 theme components 52:61 arg1 identification 25:38 identification 25:38 identification 25:38 Rapid classification and identification of chemical components of Astragali radix by UPLC-Q-TOF-MS. 35726352 0 60 theme components 52:61 arg1 classification 6:19 Rapid classification 0:19 Rapid classification 0:19 Rapid classification and identification of chemical components of Astragali radix by UPLC-Q-TOF-MS. 35726352 9 61 theme constituents 1296:1307 arg1 total 1275:1279 A total 1273:1279 RESULTS A total of 45 chemical constituents 1265:1307 RESULTS A total of 45 chemical constituents were successfully screened out, including 22 flavonoids, 13 saponins, and 10 amino acids. 35726352 6 62 theme ultra-high-performance 831:852 arg1 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 6 62 theme ultra-high-performance 831:852 arg1 spectrometry 907:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry 831:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) 831:934 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 7 63 theme negative 1041:1048 arg1 modes 1054:1058 the positive and negative ion modes 1024:1058 the positive and negative ion modes 1024:1058 Firstly, fragmentation information was obtained in the positive and negative ion modes. 35726352 2 64 theme main 348:351 arg1 acids 313:317 amino acids 307:317 amino acids 307:317 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 64 theme main 348:351 arg1 polysaccharides 324:338 polysaccharides 324:338 polysaccharides 324:338 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 64 theme main 348:351 arg1 saponins 297:304 saponins 297:304 saponins 297:304 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 64 theme main 348:351 arg1 components 360:369 the main active components 344:369 the main active components in AR 344:375 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 2 64 theme main 348:351 arg1 Flavonoids 285:294 Flavonoids 285:294 Flavonoids 285:294 Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. 35726352 4 65 theme urgent 531:536 arg1 need 538:541 an urgent need 528:541 an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR 528:642 Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. 35726352 5 66 theme rapid 681:685 arg1 classification 687:700 rapid classification 681:700 rapid classification 681:700 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 7 67 theme ion 1050:1052 arg1 modes 1054:1058 the positive and negative ion modes 1024:1058 the positive and negative ion modes 1024:1058 Firstly, fragmentation information was obtained in the positive and negative ion modes. 35726352 3 68 theme medicine 492:499 arg1 analysis 455:462 the analysis 451:462 the analysis of this traditional Chinese medicine (TCM) 451:505 However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). 35726352 9 69 dep RESULTS 1265:1271 arg1 total 1275:1279 A total 1273:1279 RESULTS A total of 45 chemical constituents 1265:1307 RESULTS A total of 45 chemical constituents were successfully screened out, including 22 flavonoids, 13 saponins, and 10 amino acids. 35726352 8 70 theme characteristic 1144:1157 arg1 CFs 1175:1177 CFs 1175:1177 CFs 1175:1177 Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. 35726352 8 70 theme characteristic 1144:1157 arg1 fragmentations 1159:1172 the characteristic fragmentations 1140:1172 the characteristic fragmentations (CFs) 1140:1178 Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. 35726352 7 71 theme positive 1028:1035 arg1 modes 1054:1058 the positive and negative ion modes 1024:1058 the positive and negative ion modes 1024:1058 Firstly, fragmentation information was obtained in the positive and negative ion modes. 35726352 1 72 theme antiviral 246:254 arg1 activities 273:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities 204:282 INTRODUCTION Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. 35726352 6 73 theme time-of-flight 876:889 arg1 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 UPLC-Q-TOF-MS 921:933 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 6 73 theme time-of-flight 876:889 arg1 spectrometry 907:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry 831:918 ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) 831:934 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 5 74 from saponins 759:766 arg1 AR 788:789 AR 788:789 AR 788:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 10 75 dep realised 1433:1440 arg1 provided 1553:1560 provided 1553:1560 provided a basis for further study on AR 1553:1592 CONCLUSION The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR. 35726352 4 76 theme chemical 616:623 arg1 constituents 625:636 the chemical constituents 612:636 the chemical constituents in AR 612:642 Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. 35726352 0 77 theme Astragali 66:74 arg1 components 52:61 chemical components 43:61 chemical components of Astragali radix 43:80 Rapid classification and identification of chemical components of Astragali radix by UPLC-Q-TOF-MS. 35726352 6 78 theme post-processing 945:959 arg1 techniques 961:970 data post-processing techniques 940:970 data post-processing techniques 940:970 METHODS The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. 35726352 8 79 theme AR 1125:1126 arg1 components 1128:1137 AR components 1125:1137 AR components 1125:1137 Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. 35726352 5 80 theme components 733:742 arg1 identification 706:719 identification 706:719 identification of the main components of flavonoids, saponins, and amino acids in AR 706:789 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 35726352 5 80 theme components 733:742 arg1 classification 687:700 rapid classification 681:700 rapid classification 681:700 OBJECTIVE To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. 37336456 1 0 theme biosolid 258:265 arg1 treatment 267:275 biosolid treatment 258:275 biosolid treatment 258:275 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 2 1 theme zeolite 486:492 arg1 sizes 477:481 particle sizes 468:481 particle sizes of zeolite 468:492 This study investigated response mechanisms of anaerobic digestion of waste activated sludge (WAS) to particle sizes of zeolite. 37336456 1 2 theme above 351:355 arg1 process 357:363 the above process 347:363 the above process 347:363 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 3 3 theme volatile 565:572 arg1 VSS 592:594 VSS 592:594 VSS 592:594 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 3 3 theme volatile 565:572 arg1 solids 584:589 186.75 ± 7.62 mL/g volatile suspended solids 546:589 186.75 ± 7.62 mL/g volatile suspended solids (VSS) 546:595 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 0 4 theme particle 85:92 arg1 sizes 94:98 particle sizes 85:98 particle sizes of zeolite 85:109 Insights into response mechanism of anaerobic digestion of waste activated sludge to particle sizes of zeolite. 37336456 3 5 theme suspended 574:582 arg1 VSS 592:594 VSS 592:594 VSS 592:594 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 3 5 theme suspended 574:582 arg1 solids 584:589 186.75 ± 7.62 mL/g volatile suspended solids 546:589 186.75 ± 7.62 mL/g volatile suspended solids (VSS) 546:595 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 0 6 theme zeolite 103:109 arg1 sizes 94:98 particle sizes 85:98 particle sizes of zeolite 85:109 Insights into response mechanism of anaerobic digestion of waste activated sludge to particle sizes of zeolite. 37336456 2 7 theme waste 436:440 arg1 sludge 452:457 waste activated sludge 436:457 waste activated sludge (WAS) 436:463 This study investigated response mechanisms of anaerobic digestion of waste activated sludge (WAS) to particle sizes of zeolite. 37336456 1 8 theme promising 155:163 arg1 alternative 324:334 a potential alternative 312:334 a potential alternative to promote the above process 312:363 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 1 8 theme promising 155:163 arg1 strategy 165:172 one promising strategy 151:172 one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials 151:307 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 3 9 theme 186.75 ± 7.62 mL/g 546:563 arg1 VSS 592:594 VSS 592:594 VSS 592:594 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 3 9 theme 186.75 ± 7.62 mL/g 546:563 arg1 solids 584:589 186.75 ± 7.62 mL/g volatile suspended solids 546:589 186.75 ± 7.62 mL/g volatile suspended solids (VSS) 546:595 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 4 10 dep hydrolysis 789:798 arg1 stages 835:840 stages 835:840 stages 835:840 Mechanism study revealed that zeolite could improve hydrolysis, acidification, and methanogenesis stages. 37336456 5 11 theme SCFAs 1004:1008 arg1 compositions 988:999 the compositions 984:999 the compositions of SCFAs 984:1008 Rapid consumption rates of soluble polysaccharides and proteins were observed, correspondingly, the accumulation of SCFAs were enhanced, and the compositions of SCFAs were optimized. 37336456 5 12 theme soluble 870:876 arg1 polysaccharides 878:892 soluble polysaccharides 870:892 soluble polysaccharides 870:892 Rapid consumption rates of soluble polysaccharides and proteins were observed, correspondingly, the accumulation of SCFAs were enhanced, and the compositions of SCFAs were optimized. 37336456 2 13 theme response 390:397 arg1 mechanisms 399:408 response mechanisms 390:408 response mechanisms of anaerobic digestion of waste activated sludge (WAS) 390:463 This study investigated response mechanisms of anaerobic digestion of waste activated sludge (WAS) to particle sizes of zeolite. 37336456 5 14 theme Rapid 843:847 arg1 rates 861:865 Rapid consumption rates 843:865 Rapid consumption rates of soluble polysaccharides and proteins 843:905 Rapid consumption rates of soluble polysaccharides and proteins were observed, correspondingly, the accumulation of SCFAs were enhanced, and the compositions of SCFAs were optimized. 37336456 1 15 theme exogenous 289:297 arg1 materials 299:307 exogenous materials 289:307 exogenous materials 289:307 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 4 16 theme Mechanism 737:745 arg1 study 747:751 Mechanism study 737:751 Mechanism study 737:751 Mechanism study revealed that zeolite could improve hydrolysis, acidification, and methanogenesis stages. 37336456 2 17 theme activated 442:450 arg1 sludge 452:457 waste activated sludge 436:457 waste activated sludge (WAS) 436:463 This study investigated response mechanisms of anaerobic digestion of waste activated sludge (WAS) to particle sizes of zeolite. 37336456 2 18 theme sludge 452:457 arg1 digestion 423:431 anaerobic digestion 413:431 anaerobic digestion of waste activated sludge (WAS) 413:463 This study investigated response mechanisms of anaerobic digestion of waste activated sludge (WAS) to particle sizes of zeolite. 37336456 3 19 theme additive 653:660 arg1 dosage 662:667 the additive dosage 649:667 the additive dosage of 0.1 g/g VSS 649:682 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 1 20 theme resource 200:207 arg1 recovery 209:216 resource recovery 200:216 resource recovery 200:216 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 0 21 theme anaerobic 36:44 arg1 digestion 46:54 anaerobic digestion 36:54 anaerobic digestion of waste 36:63 Insights into response mechanism of anaerobic digestion of waste activated sludge to particle sizes of zeolite. 37336456 3 22 theme dosage 662:667 arg1 size 626:629 the particle size 613:629 the particle size 613:629 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 5 23 theme polysaccharides 878:892 arg1 rates 861:865 Rapid consumption rates 843:865 Rapid consumption rates of soluble polysaccharides and proteins 843:905 Rapid consumption rates of soluble polysaccharides and proteins were observed, correspondingly, the accumulation of SCFAs were enhanced, and the compositions of SCFAs were optimized. 37336456 1 24 theme recovery 209:216 arg1 control 246:252 resource recovery and environmental pollution control 200:252 resource recovery and environmental pollution control for biosolid treatment 200:275 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 2 25 theme anaerobic 413:421 arg1 digestion 423:431 anaerobic digestion 413:431 anaerobic digestion of waste activated sludge (WAS) 413:463 This study investigated response mechanisms of anaerobic digestion of waste activated sludge (WAS) to particle sizes of zeolite. 37336456 5 26 theme consumption 849:859 arg1 rates 861:865 Rapid consumption rates 843:865 Rapid consumption rates of soluble polysaccharides and proteins 843:905 Rapid consumption rates of soluble polysaccharides and proteins were observed, correspondingly, the accumulation of SCFAs were enhanced, and the compositions of SCFAs were optimized. 37336456 2 27 theme digestion 423:431 arg1 mechanisms 399:408 response mechanisms 390:408 response mechanisms of anaerobic digestion of waste activated sludge (WAS) 390:463 This study investigated response mechanisms of anaerobic digestion of waste activated sludge (WAS) to particle sizes of zeolite. 37336456 2 28 theme particle 468:475 arg1 sizes 477:481 particle sizes 468:481 particle sizes of zeolite 468:492 This study investigated response mechanisms of anaerobic digestion of waste activated sludge (WAS) to particle sizes of zeolite. 37336456 1 29 theme potential 314:322 arg1 alternative 324:334 a potential alternative 312:334 a potential alternative to promote the above process 312:363 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 1 29 theme potential 314:322 arg1 strategy 165:172 one promising strategy 151:172 one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials 151:307 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 0 30 theme digestion 46:54 arg1 mechanism 23:31 response mechanism 14:31 response mechanism of anaerobic digestion of waste 14:63 Insights into response mechanism of anaerobic digestion of waste activated sludge to particle sizes of zeolite. 37336456 3 31 theme VSS 680:682 arg1 dosage 662:667 the additive dosage 649:667 the additive dosage of 0.1 g/g VSS 649:682 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 3 31 theme VSS 680:682 arg1 0.2-0.5 mm 634:643 0.2-0.5 mm 634:643 0.2-0.5 mm 634:643 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 1 32 dep strategy 165:172 arg1 adding 282:287 adding 282:287 adding exogenous materials 282:307 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 1 32 dep strategy 165:172 arg1 achieve 192:198 achieve 192:198 to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment 174:275 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 1 33 theme Anaerobic 112:120 arg1 digestion 122:130 Anaerobic digestion 112:130 Anaerobic digestion 112:130 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 3 34 theme size 626:629 arg1 zeolite 602:608 zeolite 602:608 zeolite 602:608 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 6 35 theme syntrophic 1098:1107 arg1 metabolism 1109:1118 the syntrophic metabolism 1094:1118 the syntrophic metabolism between bacteria and methanogens 1094:1151 Moreover, the activities of F420 increased by 28% with zeolite, and the syntrophic metabolism between bacteria and methanogens were promoted. 37336456 5 36 theme SCFAs 959:963 arg1 accumulation 943:954 the accumulation 939:954 the accumulation of SCFAs 939:963 Rapid consumption rates of soluble polysaccharides and proteins were observed, correspondingly, the accumulation of SCFAs were enhanced, and the compositions of SCFAs were optimized. 37336456 1 37 theme environmental 222:234 arg1 pollution 236:244 environmental pollution 222:244 environmental pollution 222:244 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 3 38 theme 0.2-0.5 mm 634:643 arg1 size 626:629 the particle size 613:629 the particle size 613:629 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 1 39 theme pollution 236:244 arg1 control 246:252 resource recovery and environmental pollution control 200:252 resource recovery and environmental pollution control for biosolid treatment 200:275 Anaerobic digestion has been proved as one promising strategy to simultaneously achieve resource recovery and environmental pollution control for biosolid treatment, and adding exogenous materials is a potential alternative to promote the above process. 37336456 3 40 theme 0.1 g/g 672:678 arg1 VSS 680:682 0.1 g/g VSS 672:682 0.1 g/g VSS 672:682 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 3 41 theme particle 617:624 arg1 size 626:629 the particle size 613:629 the particle size 613:629 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 6 42 theme F420 1054:1057 arg1 activities 1040:1049 the activities 1036:1049 the activities of F420 1036:1057 Moreover, the activities of F420 increased by 28% with zeolite, and the syntrophic metabolism between bacteria and methanogens were promoted. 37336456 3 43 theme methane 519:525 arg1 production 527:536 the methane production 515:536 the methane production 515:536 Results showed that the methane production reached 186.75 ± 7.62 mL/g volatile suspended solids (VSS) with zeolite of the particle size of 0.2-0.5 mm and the additive dosage of 0.1 g/g VSS, which increased by 22% compared to that in control. 37336456 0 44 theme waste 59:63 arg1 digestion 46:54 anaerobic digestion 36:54 anaerobic digestion of waste 36:63 Insights into response mechanism of anaerobic digestion of waste activated sludge to particle sizes of zeolite. 37336456 0 45 theme response 14:21 arg1 mechanism 23:31 response mechanism 14:31 response mechanism of anaerobic digestion of waste 14:63 Insights into response mechanism of anaerobic digestion of waste activated sludge to particle sizes of zeolite. 37336456 5 46 theme proteins 898:905 arg1 rates 861:865 Rapid consumption rates 843:865 Rapid consumption rates of soluble polysaccharides and proteins 843:905 Rapid consumption rates of soluble polysaccharides and proteins were observed, correspondingly, the accumulation of SCFAs were enhanced, and the compositions of SCFAs were optimized. 35868824 7 0 theme Ultra-performance 1219:1235 arg1 chromatography 1244:1257 Ultra-performance liquid chromatography 1219:1257 Ultra-performance liquid chromatography 1219:1257 Ultra-performance liquid chromatography will be performed to separate and detect IgG N-glycans in serum collected at baseline and at the end of the first, second and third years. 35868824 2 1 theme risk 404:407 arg1 score 409:413 the 10-year atherosclerotic cardiovascular disease risk score 353:413 the 10-year atherosclerotic cardiovascular disease risk score 353:413 IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. 35868824 1 2 theme atherosclerosis 282:296 arg1 pathogenesis 266:277 the pathogenesis 262:277 the pathogenesis of atherosclerosis 262:296 INTRODUCTION Immune-inflammatory response plays a key role in the pathogenesis of atherosclerosis. 35868824 4 3 theme glycosylation 657:669 arg1 traits 671:676 IgG glycosylation traits 653:676 IgG glycosylation traits 653:676 Therefore, this study aims to understand whether IgG glycosylation traits are correlated with actual clinical CVD events and plaque phenotypes. 35868824 4 4 theme plaque 729:734 arg1 phenotypes 736:745 plaque phenotypes 729:745 plaque phenotypes 729:745 Therefore, this study aims to understand whether IgG glycosylation traits are correlated with actual clinical CVD events and plaque phenotypes. 35868824 5 5 theme longitudinal 930:941 arg1 study 962:966 this longitudinal prospective cohort study 925:966 this longitudinal prospective cohort study 925:966 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 10 6 from publication 1787:1797 arg1 journals 1816:1823 peer-reviewed journals 1802:1823 peer-reviewed journals 1802:1823 Findings of this study will be submitted for publication in peer-reviewed journals. 35868824 1 7 theme Immune-inflammatory 213:231 arg1 response 233:240 INTRODUCTION Immune-inflammatory response 200:240 INTRODUCTION Immune-inflammatory response 200:240 INTRODUCTION Immune-inflammatory response plays a key role in the pathogenesis of atherosclerosis. 35868824 4 8 theme clinical 705:712 arg1 events 718:723 actual clinical CVD events 698:723 actual clinical CVD events 698:723 Therefore, this study aims to understand whether IgG glycosylation traits are correlated with actual clinical CVD events and plaque phenotypes. 35868824 5 9 theme atherosclerosis 897:911 arg1 occurrence 913:922 atherosclerosis occurrence 897:922 atherosclerosis occurrence 897:922 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 8 10 theme coronary 1519:1526 arg1 disease 1534:1540 coronary heart disease 1519:1540 coronary heart disease 1519:1540 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 5 11 theme CVD 882:884 arg1 biomarkers 868:877 potential biomarkers 858:877 potential biomarkers of CVD 858:884 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 1 12 theme key 250:252 arg1 role 254:257 a key role 248:257 a key role 248:257 INTRODUCTION Immune-inflammatory response plays a key role in the pathogenesis of atherosclerosis. 35868824 0 13 theme prospective 174:184 arg1 study 193:197 a longitudinal prospective cohort study 159:197 a longitudinal prospective cohort study 159:197 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 5 14 theme Affiliated 999:1008 arg1 Hospital 1010:1017 the First Affiliated Hospital 989:1017 the First Affiliated Hospital of Shantou University Medical College, China 989:1062 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 5 15 theme First 993:997 arg1 Hospital 1010:1017 the First Affiliated Hospital 989:1017 the First Affiliated Hospital of Shantou University Medical College, China 989:1062 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 5 16 theme CVD 836:838 arg1 events 840:845 CVD events 836:845 CVD events 836:845 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 9 17 theme Ethics 1612:1617 arg1 Committee 1619:1627 ETHICS AND DISSEMINATION The Clinical Ethics Committee 1574:1627 Committee 1619:1627 ETHICS AND DISSEMINATION The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). 35868824 0 18 dep plaque 77:82 arg1 phenotypes 84:93 phenotypes 84:93 phenotypes 84:93 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 0 19 theme clinical 106:113 arg1 events 130:135 actual clinical cardiovascular events 99:135 actual clinical cardiovascular events 99:135 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 8 20 theme clinical 1432:1439 arg1 death 1506:1510 death 1506:1510 death due to coronary heart disease 1506:1540 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 20 theme clinical 1432:1439 arg1 stroke 1566:1571 fatal or non-fatal stroke 1547:1571 fatal or non-fatal stroke 1547:1571 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 20 theme clinical 1432:1439 arg1 infarction 1494:1503 non-fatal myocardial infarction 1473:1503 non-fatal myocardial infarction 1473:1503 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 20 theme clinical 1432:1439 arg1 events 1455:1460 the actual clinical CVD composite events 1421:1460 the actual clinical CVD composite events 1421:1460 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 20 theme clinical 1432:1439 arg1 outcome 1410:1416 The primary outcome 1398:1416 The primary outcome 1398:1416 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 3 21 theme actual 500:505 arg1 events 545:550 actual clinical cardiovascular disease (CVD) events 500:550 actual clinical cardiovascular disease (CVD) events 500:550 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 7 22 theme IgG 1300:1302 arg1 N-glycans 1304:1312 IgG N-glycans 1300:1312 IgG N-glycans 1300:1312 Ultra-performance liquid chromatography will be performed to separate and detect IgG N-glycans in serum collected at baseline and at the end of the first, second and third years. 35868824 9 23 theme First 1636:1640 arg1 Hospital 1653:1660 the First Affiliated Hospital 1632:1660 the First Affiliated Hospital of Shantou University 1632:1682 ETHICS AND DISSEMINATION The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). 35868824 8 24 theme composite 1445:1453 arg1 death 1506:1510 death 1506:1510 death due to coronary heart disease 1506:1540 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 24 theme composite 1445:1453 arg1 stroke 1566:1571 fatal or non-fatal stroke 1547:1571 fatal or non-fatal stroke 1547:1571 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 24 theme composite 1445:1453 arg1 infarction 1494:1503 non-fatal myocardial infarction 1473:1503 non-fatal myocardial infarction 1473:1503 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 24 theme composite 1445:1453 arg1 events 1455:1460 the actual clinical CVD composite events 1421:1460 the actual clinical CVD composite events 1421:1460 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 24 theme composite 1445:1453 arg1 outcome 1410:1416 The primary outcome 1398:1416 The primary outcome 1398:1416 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 3 25 theme glycosylation 481:493 arg1 relationship 461:472 the relationship 457:472 the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes 457:572 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 9 26 theme Hospital 1653:1660 arg1 Committee 1619:1627 ETHICS AND DISSEMINATION The Clinical Ethics Committee 1574:1627 Committee 1619:1627 ETHICS AND DISSEMINATION The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). 35868824 10 27 theme study 1759:1763 arg1 Findings 1742:1749 Findings 1742:1749 Findings of this study 1742:1763 Findings of this study will be submitted for publication in peer-reviewed journals. 35868824 0 28 theme immunoglobulin 15:28 arg1 N-glycosylation 32:46 immunoglobulin G N-glycosylation 15:46 immunoglobulin G N-glycosylation 15:46 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 5 29 theme University 1030:1039 arg1 Hospital 1010:1017 the First Affiliated Hospital 989:1017 the First Affiliated Hospital of Shantou University Medical College, China 989:1062 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 7 30 theme years 1391:1395 arg1 end 1356:1358 the end 1352:1358 the end of the first, second and third years 1352:1395 Ultra-performance liquid chromatography will be performed to separate and detect IgG N-glycans in serum collected at baseline and at the end of the first, second and third years. 35868824 6 31 theme carotid 1115:1121 arg1 ultrasound 1123:1132 carotid ultrasound 1115:1132 carotid ultrasound 1115:1132 In total, 2720 participants routinely examined by carotid ultrasound will be divided into different groups according to plaque phenotype characteristics. 35868824 8 32 theme non-fatal 1473:1481 arg1 infarction 1494:1503 non-fatal myocardial infarction 1473:1503 non-fatal myocardial infarction 1473:1503 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 3 33 theme cardiovascular 516:529 arg1 disease 531:537 clinical cardiovascular disease 507:537 actual clinical cardiovascular disease (CVD) events 500:550 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 3 33 theme cardiovascular 516:529 arg1 CVD 540:542 CVD 540:542 CVD 540:542 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 0 34 theme N-glycosylation 32:46 arg1 Association 0:10 Association 0:10 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 0:198 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 2 35 theme disease 396:402 arg1 score 409:413 the 10-year atherosclerotic cardiovascular disease risk score 353:413 the 10-year atherosclerotic cardiovascular disease risk score 353:413 IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. 35868824 5 36 theme potential 858:866 arg1 biomarkers 868:877 potential biomarkers 858:877 potential biomarkers of CVD 858:884 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 0 37 with Association 0:10 arg1 plaque 77:82 carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events 53:135 plaque 77:82 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 0 37 with Association 0:10 arg1 events 130:135 actual clinical cardiovascular events 99:135 actual clinical cardiovascular events 99:135 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 2 38 theme atherosclerotic 365:379 arg1 score 409:413 the 10-year atherosclerotic cardiovascular disease risk score 353:413 the 10-year atherosclerotic cardiovascular disease risk score 353:413 IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. 35868824 6 39 theme phenotype 1192:1200 arg1 characteristics 1202:1216 plaque phenotype characteristics 1185:1216 plaque phenotype characteristics 1185:1216 In total, 2720 participants routinely examined by carotid ultrasound will be divided into different groups according to plaque phenotype characteristics. 35868824 2 40 theme subclinical 419:429 arg1 atherosclerosis 431:445 subclinical atherosclerosis 419:445 subclinical atherosclerosis 419:445 IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. 35868824 7 41 theme liquid 1237:1242 arg1 chromatography 1244:1257 Ultra-performance liquid chromatography 1219:1257 Ultra-performance liquid chromatography 1219:1257 Ultra-performance liquid chromatography will be performed to separate and detect IgG N-glycans in serum collected at baseline and at the end of the first, second and third years. 35868824 0 42 dep Association 0:10 arg1 protocol 146:153 a study protocol 138:153 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 0:198 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 3 43 with relationship 461:472 arg1 events 545:550 actual clinical cardiovascular disease (CVD) events 500:550 actual clinical cardiovascular disease (CVD) events 500:550 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 3 43 with relationship 461:472 arg1 phenotypes 563:572 plaque phenotypes 556:572 plaque phenotypes 556:572 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 4 44 theme IgG 653:655 arg1 traits 671:676 IgG glycosylation traits 653:676 IgG glycosylation traits 653:676 Therefore, this study aims to understand whether IgG glycosylation traits are correlated with actual clinical CVD events and plaque phenotypes. 35868824 5 45 theme prospective 943:953 arg1 study 962:966 this longitudinal prospective cohort study 925:966 this longitudinal prospective cohort study 925:966 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 0 46 theme carotid 53:59 arg1 plaque 77:82 carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events 53:135 plaque 77:82 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 9 47 dep approved 1700:1707 arg1 study 1714:1718 this study 1709:1718 this study (number: B-2021-127) 1709:1739 ETHICS AND DISSEMINATION The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). 35868824 1 48 theme INTRODUCTION 200:211 arg1 response 233:240 INTRODUCTION Immune-inflammatory response 200:240 INTRODUCTION Immune-inflammatory response 200:240 INTRODUCTION Immune-inflammatory response plays a key role in the pathogenesis of atherosclerosis. 35868824 0 49 theme study 140:144 arg1 protocol 146:153 a study protocol 138:153 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 0:198 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 8 50 theme heart 1528:1532 arg1 disease 1534:1540 coronary heart disease 1519:1540 coronary heart disease 1519:1540 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 9 51 dep number 1721:1726 arg1 B-2021-127 1729:1738 B-2021-127 1729:1738 number: B-2021-127 1721:1738 ETHICS AND DISSEMINATION The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). 35868824 2 52 theme cardiovascular 381:394 arg1 score 409:413 the 10-year atherosclerotic cardiovascular disease risk score 353:413 the 10-year atherosclerotic cardiovascular disease risk score 353:413 IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. 35868824 5 53 theme cohort 955:960 arg1 study 962:966 this longitudinal prospective cohort study 925:966 this longitudinal prospective cohort study 925:966 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 9 54 dep study 1714:1718 arg1 number 1721:1726 number 1721:1726 number: B-2021-127 1721:1738 ETHICS AND DISSEMINATION The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). 35868824 0 55 theme longitudinal 161:172 arg1 study 193:197 a longitudinal prospective cohort study 159:197 a longitudinal prospective cohort study 159:197 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 8 56 theme fatal 1547:1551 arg1 stroke 1566:1571 fatal or non-fatal stroke 1547:1571 fatal or non-fatal stroke 1547:1571 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 0 57 theme cohort 186:191 arg1 study 193:197 a longitudinal prospective cohort study 159:197 a longitudinal prospective cohort study 159:197 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 2 58 theme IgG 299:301 arg1 N-glycosylation 303:317 IgG N-glycosylation 299:317 IgG N-glycosylation 299:317 IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. 35868824 9 59 theme ETHICS 1574:1579 arg1 Committee 1619:1627 ETHICS AND DISSEMINATION The Clinical Ethics Committee 1574:1627 Committee 1619:1627 ETHICS AND DISSEMINATION The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). 35868824 8 60 theme non-fatal 1556:1564 arg1 stroke 1566:1571 fatal or non-fatal stroke 1547:1571 fatal or non-fatal stroke 1547:1571 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 5 61 dep University 1030:1039 arg1 China 1058:1062 China 1058:1062 China 1058:1062 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 5 62 theme IgG 804:806 arg1 glycosylation 808:820 IgG glycosylation 804:820 IgG glycosylation 804:820 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 0 63 theme actual 99:104 arg1 events 130:135 actual clinical cardiovascular events 99:135 actual clinical cardiovascular events 99:135 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 9 64 theme Clinical 1603:1610 arg1 Committee 1619:1627 ETHICS AND DISSEMINATION The Clinical Ethics Committee 1574:1627 Committee 1619:1627 ETHICS AND DISSEMINATION The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). 35868824 8 65 theme primary 1402:1408 arg1 death 1506:1510 death 1506:1510 death due to coronary heart disease 1506:1540 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 65 theme primary 1402:1408 arg1 stroke 1566:1571 fatal or non-fatal stroke 1547:1571 fatal or non-fatal stroke 1547:1571 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 65 theme primary 1402:1408 arg1 infarction 1494:1503 non-fatal myocardial infarction 1473:1503 non-fatal myocardial infarction 1473:1503 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 65 theme primary 1402:1408 arg1 events 1455:1460 the actual clinical CVD composite events 1421:1460 the actual clinical CVD composite events 1421:1460 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 65 theme primary 1402:1408 arg1 outcome 1410:1416 The primary outcome 1398:1416 The primary outcome 1398:1416 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 0 66 theme cardiovascular 115:128 arg1 events 130:135 actual clinical cardiovascular events 99:135 actual clinical cardiovascular events 99:135 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 5 67 theme glycosylation 808:820 arg1 risk 827:830 a risk 825:830 a risk for CVD events 825:845 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 5 67 theme glycosylation 808:820 arg1 efficacy 792:799 the efficacy 788:799 the efficacy of IgG glycosylation 788:820 METHODS AND ANALYSIS Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. 35868824 4 68 theme actual 698:703 arg1 events 718:723 actual clinical CVD events 698:723 actual clinical CVD events 698:723 Therefore, this study aims to understand whether IgG glycosylation traits are correlated with actual clinical CVD events and plaque phenotypes. 35868824 6 69 theme different 1155:1163 arg1 groups 1165:1170 different groups 1155:1170 different groups according to plaque phenotype characteristics 1155:1216 In total, 2720 participants routinely examined by carotid ultrasound will be divided into different groups according to plaque phenotype characteristics. 35868824 8 70 theme actual 1425:1430 arg1 death 1506:1510 death 1506:1510 death due to coronary heart disease 1506:1540 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 70 theme actual 1425:1430 arg1 stroke 1566:1571 fatal or non-fatal stroke 1547:1571 fatal or non-fatal stroke 1547:1571 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 70 theme actual 1425:1430 arg1 infarction 1494:1503 non-fatal myocardial infarction 1473:1503 non-fatal myocardial infarction 1473:1503 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 70 theme actual 1425:1430 arg1 events 1455:1460 the actual clinical CVD composite events 1421:1460 the actual clinical CVD composite events 1421:1460 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 70 theme actual 1425:1430 arg1 outcome 1410:1416 The primary outcome 1398:1416 The primary outcome 1398:1416 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 3 71 theme clinical 507:514 arg1 disease 531:537 clinical cardiovascular disease 507:537 actual clinical cardiovascular disease (CVD) events 500:550 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 3 71 theme clinical 507:514 arg1 CVD 540:542 CVD 540:542 CVD 540:542 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 9 72 theme Affiliated 1642:1651 arg1 Hospital 1653:1660 the First Affiliated Hospital 1632:1660 the First Affiliated Hospital of Shantou University 1632:1682 ETHICS AND DISSEMINATION The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). 35868824 8 73 theme CVD 1441:1443 arg1 death 1506:1510 death 1506:1510 death due to coronary heart disease 1506:1540 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 73 theme CVD 1441:1443 arg1 stroke 1566:1571 fatal or non-fatal stroke 1547:1571 fatal or non-fatal stroke 1547:1571 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 73 theme CVD 1441:1443 arg1 infarction 1494:1503 non-fatal myocardial infarction 1473:1503 non-fatal myocardial infarction 1473:1503 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 73 theme CVD 1441:1443 arg1 events 1455:1460 the actual clinical CVD composite events 1421:1460 the actual clinical CVD composite events 1421:1460 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 8 73 theme CVD 1441:1443 arg1 outcome 1410:1416 The primary outcome 1398:1416 The primary outcome 1398:1416 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 0 74 theme G 30:30 arg1 N-glycosylation 32:46 immunoglobulin G N-glycosylation 15:46 immunoglobulin G N-glycosylation 15:46 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 7 75 theme third 1385:1389 arg1 years 1391:1395 the first, second and third years 1363:1395 the first, second and third years 1363:1395 Ultra-performance liquid chromatography will be performed to separate and detect IgG N-glycans in serum collected at baseline and at the end of the first, second and third years. 35868824 9 76 theme University 1673:1682 arg1 Hospital 1653:1660 the First Affiliated Hospital 1632:1660 the First Affiliated Hospital of Shantou University 1632:1682 ETHICS AND DISSEMINATION The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). 35868824 7 77 theme second 1374:1379 arg1 years 1391:1395 the first, second and third years 1363:1395 the first, second and third years 1363:1395 Ultra-performance liquid chromatography will be performed to separate and detect IgG N-glycans in serum collected at baseline and at the end of the first, second and third years. 35868824 3 78 theme IgG 477:479 arg1 glycosylation 481:493 IgG glycosylation 477:493 IgG glycosylation 477:493 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 3 79 theme disease 531:537 arg1 events 545:550 actual clinical cardiovascular disease (CVD) events 500:550 actual clinical cardiovascular disease (CVD) events 500:550 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 0 80 theme atherosclerotic 61:75 arg1 plaque 77:82 carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events 53:135 plaque 77:82 Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study. 35868824 7 81 theme first 1367:1371 arg1 years 1391:1395 the first, second and third years 1363:1395 the first, second and third years 1363:1395 Ultra-performance liquid chromatography will be performed to separate and detect IgG N-glycans in serum collected at baseline and at the end of the first, second and third years. 35868824 8 82 theme myocardial 1483:1492 arg1 infarction 1494:1503 non-fatal myocardial infarction 1473:1503 non-fatal myocardial infarction 1473:1503 The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. 35868824 3 83 theme plaque 556:561 arg1 phenotypes 563:572 plaque phenotypes 556:572 plaque phenotypes 556:572 However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. 35868824 2 84 theme 10-year 357:363 arg1 score 409:413 the 10-year atherosclerotic cardiovascular disease risk score 353:413 the 10-year atherosclerotic cardiovascular disease risk score 353:413 IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. 35868824 4 85 theme CVD 714:716 arg1 events 718:723 actual clinical CVD events 698:723 actual clinical CVD events 698:723 Therefore, this study aims to understand whether IgG glycosylation traits are correlated with actual clinical CVD events and plaque phenotypes. 35868824 6 86 theme plaque 1185:1190 arg1 characteristics 1202:1216 plaque phenotype characteristics 1185:1216 plaque phenotype characteristics 1185:1216 In total, 2720 participants routinely examined by carotid ultrasound will be divided into different groups according to plaque phenotype characteristics. 35868824 10 87 theme peer-reviewed 1802:1814 arg1 journals 1816:1823 peer-reviewed journals 1802:1823 peer-reviewed journals 1802:1823 Findings of this study will be submitted for publication in peer-reviewed journals. 37079436 2 0 theme perfusion 533:541 arg1 runs 543:546 parallel perfusion runs 524:546 parallel perfusion runs 524:546 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 1 1 theme cell 377:380 arg1 density 382:388 high cell density 372:388 high cell density continuous mode 372:404 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 1 2 theme continuous 390:399 arg1 mode 401:404 high cell density continuous mode 372:404 high cell density continuous mode 372:404 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 1 3 theme key 231:233 arg1 substrates 235:244 key substrates 231:244 key substrates of the culture medium 231:266 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 2 4 theme amino 654:658 arg1 mixtures 665:672 different amino acid mixtures 644:672 different amino acid mixtures 644:672 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 2 5 from behavior 620:627 arg1 presence 632:639 presence 632:639 presence of different amino acid mixtures 632:672 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 5 6 theme 17 pL/cell/day 1524:1537 arg1 densities 1437:1445 very high cell densities 1422:1445 very high cell densities of 60 × 106 and 120 × 106 cells/mL 1422:1480 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 5 6 theme 17 pL/cell/day 1524:1537 arg1 rate 1516:1519 a low cell-specific perfusion rate 1486:1519 a low cell-specific perfusion rate of 17 pL/cell/day 1486:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 5 7 theme stable 1359:1364 arg1 cultures 1399:1406 stable Chinese hamster ovary (CHO) cell cultures 1359:1406 stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day 1359:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 2 8 theme mixtures 665:672 arg1 presence 632:639 presence 632:639 presence of different amino acid mixtures 632:672 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 5 9 theme hamster 1374:1380 arg1 cultures 1399:1406 stable Chinese hamster ovary (CHO) cell cultures 1359:1406 stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day 1359:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 1 10 theme design 167:172 arg1 approach 155:162 A novel approach 147:162 A novel approach of design of experiment (DoE) 147:192 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 2 11 theme consumption 703:713 arg1 rates 715:719 targeted specific consumption rates 685:719 targeted specific consumption rates 685:719 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 1 12 theme experiment 177:186 arg1 design 167:172 design 167:172 design of experiment (DoE) 167:192 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 2 13 theme targeted 685:692 arg1 rates 715:719 targeted specific consumption rates 685:719 targeted specific consumption rates 685:719 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 1 14 theme working 344:350 arg1 volume 352:357 working volume 344:357 working volume 344:357 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 2 15 theme medium 507:512 arg1 blends 514:519 multiple medium blends 498:519 multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures 498:672 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 3 16 theme culture 783:789 arg1 G1 841:842 G1 841:842 G1 841:842 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 3 16 theme culture 783:789 arg1 parameters 791:800 the culture parameters 779:800 the culture parameters 779:800 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 3 16 theme culture 783:789 arg1 attributes 822:831 product quality attributes 806:831 product quality attributes 806:831 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 3 16 theme culture 783:789 arg1 G0 834:835 G0 834:835 G0 834:835 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 3 16 theme culture 783:789 arg1 function of 866:876 a function of the medium composition 864:899 a function of the medium composition 864:899 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 1 17 theme density 382:388 arg1 mode 401:404 high cell density continuous mode 372:404 high cell density continuous mode 372:404 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 3 18 theme optimized 725:733 arg1 medium 735:740 An optimized medium 722:740 An optimized medium 722:740 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 2 19 theme culture 612:618 arg1 behavior 620:627 the culture behavior 608:627 the culture behavior in presence of different amino acid mixtures 608:672 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 4 20 theme tangential 1081:1090 arg1 filtration 1097:1106 tangential flow filtration 1081:1106 tangential flow filtration (TFF) for cell separation 1081:1132 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 20 theme tangential 1081:1090 arg1 TFF 1109:1111 TFF 1109:1111 TFF 1109:1111 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 0 21 theme density 64:70 arg1 cultures 81:88 high density CHO cell cultures 59:88 high density CHO cell cultures 59:88 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 3 22 theme quality 814:820 arg1 parameters 791:800 the culture parameters 779:800 the culture parameters 779:800 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 3 22 theme quality 814:820 arg1 function of 866:876 a function of the medium composition 864:899 a function of the medium composition 864:899 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 3 22 theme quality 814:820 arg1 attributes 822:831 product quality attributes 806:831 product quality attributes 806:831 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 5 23 theme high 1427:1430 arg1 densities 1437:1445 very high cell densities 1422:1445 very high cell densities of 60 × 106 and 120 × 106 cells/mL 1422:1480 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 4 24 gly N-glycosylation 1185:1199 arg1 antibody 1225:1232 the produced antibody 1212:1232 the produced antibody 1212:1232 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 0 25 theme cell 76:79 arg1 cultures 81:88 high density CHO cell cultures 59:88 high density CHO cell cultures 59:88 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 1 26 theme sugars 286:291 arg1 optimization 215:226 the optimization 211:226 the optimization of key substrates of the culture medium, amino acids, and sugars 211:291 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 2 27 theme acid 660:663 arg1 mixtures 665:672 different amino acid mixtures 644:672 different amino acid mixtures 644:672 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 2 28 theme amino 559:563 arg1 acids 565:569 the amino acids 555:569 the amino acids concentrations 555:584 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 5 29 theme present 1270:1276 arg1 strategy 1290:1297 the present development strategy 1266:1297 the present development strategy 1266:1297 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 0 30 theme low 98:100 arg1 rate 110:113 very low renewal rate 93:113 very low renewal rate 93:113 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 1 31 theme perfusion 307:315 arg1 microbioreactors 317:332 perfusion microbioreactors 307:332 perfusion microbioreactors with 2 mL 307:342 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 1 32 theme substrates 235:244 arg1 optimization 215:226 the optimization 211:226 the optimization of key substrates of the culture medium, amino acids, and sugars 211:291 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 2 33 from blends 514:519 arg1 runs 543:546 parallel perfusion runs 524:546 parallel perfusion runs 524:546 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 0 34 theme medium 16:21 arg1 Optimization 0:11 Optimization 0:11 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate 0:113 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 3 35 theme level 844:848 arg1 N-glycans 850:858 level N-glycans 844:858 level N-glycans 844:858 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 5 36 theme low 1488:1490 arg1 rate 1516:1519 a low cell-specific perfusion rate 1486:1519 a low cell-specific perfusion rate of 17 pL/cell/day 1486:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 0 37 theme perfusion 28:36 arg1 microbioreactors 38:53 perfusion microbioreactors 28:53 perfusion microbioreactors 28:53 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 1 38 theme medium 261:266 arg1 sugars 286:291 sugars 286:291 sugars 286:291 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 1 38 theme medium 261:266 arg1 substrates 235:244 key substrates 231:244 key substrates of the culture medium 231:266 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 1 38 theme medium 261:266 arg1 acids 275:279 amino acids 269:279 amino acids 269:279 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 4 39 theme antibody 1225:1232 arg1 profile 1201:1207 N-glycosylation profile 1185:1207 N-glycosylation profile 1185:1207 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 39 theme antibody 1225:1232 arg1 performance 1169:1179 overall a similar process performance 1143:1179 overall a similar process performance 1143:1179 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 5 40 theme optimized 1333:1341 arg1 performance 1343:1353 optimized performance 1333:1353 optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day 1333:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 1 41 theme amino 269:273 arg1 acids 275:279 amino acids 269:279 amino acids 269:279 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 2 42 dep acids 565:569 arg1 concentrations 571:584 concentrations 571:584 the amino acids concentrations 555:584 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 0 43 from rate 110:113 arg1 Optimization 0:11 Optimization 0:11 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate 0:113 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 2 44 theme parallel 524:531 arg1 runs 543:546 parallel perfusion runs 524:546 parallel perfusion runs 524:546 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 4 45 theme stirred-tank 989:1000 arg1 bioreactors 1002:1012 stirred-tank bioreactors 989:1012 stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) 989:1071 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 5 46 theme perfusion 1506:1514 arg1 rate 1516:1519 a low cell-specific perfusion rate 1486:1519 a low cell-specific perfusion rate of 17 pL/cell/day 1486:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 5 47 theme CHO 1389:1391 arg1 cultures 1399:1406 stable Chinese hamster ovary (CHO) cell cultures 1359:1406 stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day 1359:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 0 48 with medium 16:21 arg1 microbioreactors 38:53 perfusion microbioreactors 28:53 perfusion microbioreactors 28:53 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 5 49 theme cell 1394:1397 arg1 cultures 1399:1406 stable Chinese hamster ovary (CHO) cell cultures 1359:1406 stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day 1359:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 3 50 dep function of 866:876 arg1 composition 889:899 the medium composition 878:899 a function of the medium composition 864:899 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 1 51 theme novel 149:153 arg1 approach 155:162 A novel approach 147:162 A novel approach of design of experiment (DoE) 147:192 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 5 52 theme Chinese 1366:1372 arg1 cultures 1399:1406 stable Chinese hamster ovary (CHO) cell cultures 1359:1406 stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day 1359:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 4 53 theme flow 1051:1054 arg1 filtration 1056:1065 tangential flow filtration 1040:1065 tangential flow filtration (ATF) 1040:1071 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 53 theme flow 1051:1054 arg1 ATF 1068:1070 ATF 1068:1070 ATF 1068:1070 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 5 54 theme ovary  1382:1387 arg1 cultures 1399:1406 stable Chinese hamster ovary (CHO) cell cultures 1359:1406 stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day 1359:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 2 55 theme specific 694:701 arg1 rates 715:719 targeted specific consumption rates 685:719 targeted specific consumption rates 685:719 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 0 56 theme experiments 134:144 arg1 design 124:129 design 124:129 design of experiments 124:144 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 3 57 dep G0 834:835 arg1 N-glycans 850:858 level N-glycans 844:858 level N-glycans 844:858 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 2 58 theme multiple 498:505 arg1 blends 514:519 multiple medium blends 498:519 multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures 498:672 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 4 59 theme cell 1118:1121 arg1 separation 1123:1132 cell separation 1118:1132 cell separation 1118:1132 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 1 60 with microbioreactors 317:332 arg1 2 mL 339:342 2 mL 339:342 2 mL 339:342 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 4 61 theme flow 1092:1095 arg1 filtration 1097:1106 tangential flow filtration 1081:1106 tangential flow filtration (TFF) for cell separation 1081:1132 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 61 theme flow 1092:1095 arg1 TFF 1109:1111 TFF 1109:1111 TFF 1109:1111 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 62 theme tangential 1040:1049 arg1 filtration 1056:1065 tangential flow filtration 1040:1065 tangential flow filtration (ATF) 1040:1071 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 62 theme tangential 1040:1049 arg1 ATF 1068:1070 ATF 1068:1070 ATF 1068:1070 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 0 63 theme CHO 72:74 arg1 cultures 81:88 high density CHO cell cultures 59:88 high density CHO cell cultures 59:88 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 1 64 theme high 372:375 arg1 density 382:388 high cell density 372:388 high cell density continuous mode 372:404 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 2 65 theme different 644:652 arg1 mixtures 665:672 different amino acid mixtures 644:672 different amino acid mixtures 644:672 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 5 66 theme cell 1432:1435 arg1 densities 1437:1445 very high cell densities 1422:1445 very high cell densities of 60 × 106 and 120 × 106 cells/mL 1422:1480 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 4 67 theme similar 1153:1159 arg1 process 1161:1167 a similar process 1151:1167 overall a similar process performance 1143:1179 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 3 68 theme product 806:812 arg1 parameters 791:800 the culture parameters 779:800 the culture parameters 779:800 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 3 68 theme product 806:812 arg1 function of 866:876 a function of the medium composition 864:899 a function of the medium composition 864:899 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 3 68 theme product 806:812 arg1 attributes 822:831 product quality attributes 806:831 product quality attributes 806:831 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 0 69 theme renewal 102:108 arg1 rate 110:113 very low renewal rate 93:113 very low renewal rate 93:113 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 3 70 dep parameters 791:800 arg1 parameters 791:800 the culture parameters 779:800 the culture parameters 779:800 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 3 70 dep parameters 791:800 arg1 G1 841:842 G1 841:842 G1 841:842 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 3 70 dep parameters 791:800 arg1 G0 834:835 G0 834:835 G0 834:835 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 2 71 theme mixture 438:444 arg1 DoE 446:448 A mixture DoE 436:448 A mixture DoE based on a simplex-centroid 436:476 A mixture DoE based on a simplex-centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. 37079436 5 72 theme development 1278:1288 arg1 strategy 1290:1297 the present development strategy 1266:1297 the present development strategy 1266:1297 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 4 73 with comparison 973:982 arg1 filtration 1097:1106 tangential flow filtration 1081:1106 tangential flow filtration (TFF) for cell separation 1081:1132 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 73 with comparison 973:982 arg1 TFF 1109:1111 TFF 1109:1111 TFF 1109:1111 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 73 with comparison 973:982 arg1 bioreactors 1002:1012 stirred-tank bioreactors 989:1012 stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) 989:1071 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 5 74 with line 1585:1588 arg1 framework 1599:1607 the framework 1595:1607 the framework recently published by the industry 1595:1642 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 4 75 theme overall 1143:1149 arg1 performance 1169:1179 overall a similar process performance 1143:1179 overall a similar process performance 1143:1179 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 76 theme process 1161:1167 arg1 performance 1169:1179 overall a similar process performance 1143:1179 overall a similar process performance 1143:1179 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 77 theme perfusion 944:952 arg1 microbioreactor 954:968 perfusion microbioreactor 944:968 perfusion microbioreactor 944:968 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 4 78 theme produced 1216:1223 arg1 antibody 1225:1232 the produced antibody 1212:1232 the produced antibody 1212:1232 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 1 79 theme culture 253:259 arg1 medium 261:266 the culture medium 249:266 the culture medium 249:266 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 5 80 theme cell-specific 1492:1504 arg1 rate 1516:1519 a low cell-specific perfusion rate 1486:1519 a low cell-specific perfusion rate of 17 pL/cell/day 1486:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 1 81 theme design 422:427 arg1 space 429:433 the design space 418:433 the design space 418:433 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 0 82 theme high 59:62 arg1 cultures 81:88 high density CHO cell cultures 59:88 high density CHO cell cultures 59:88 Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments. 37079436 3 83 theme medium 882:887 arg1 composition 889:899 the medium composition 878:899 a function of the medium composition 864:899 An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N-glycans) as a function of the medium composition. 37079436 4 84 theme N-glycosylation 1185:1199 arg1 profile 1201:1207 N-glycosylation profile 1185:1207 N-glycosylation profile 1185:1207 It is then validated in runs performed in perfusion microbioreactor in comparison with stirred-tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N-glycosylation profile of the produced antibody. 37079436 1 85 theme acids 275:279 arg1 optimization 215:226 the optimization 211:226 the optimization of key substrates of the culture medium, amino acids, and sugars 211:291 A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. 37079436 5 86 theme cells/mL 1473:1480 arg1 densities 1437:1445 very high cell densities 1422:1445 very high cell densities of 60 × 106 and 120 × 106 cells/mL 1422:1480 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 5 86 theme cells/mL 1473:1480 arg1 rate 1516:1519 a low cell-specific perfusion rate 1486:1519 a low cell-specific perfusion rate of 17 pL/cell/day 1486:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 5 87 with medium 1321:1326 arg1 performance 1343:1353 optimized performance 1333:1353 optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day 1333:1537 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 37079436 5 88 theme perfusion 1311:1319 arg1 medium 1321:1326 a perfusion medium 1309:1326 a perfusion medium 1309:1326 These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell-specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry. 35897429 2 0 from composition 429:439 arg1 ponds 469:473 solar ponds 463:473 solar ponds from Salt Lake brine with multiple complementary analysis techniques 463:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 2 0 from composition 429:439 arg1 brine 490:494 Salt Lake brine 480:494 Salt Lake brine with multiple complementary analysis techniques 480:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 1 1 theme solar 243:247 arg1 ponds 249:253 solar ponds 243:253 solar ponds 243:253 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 1 2 dep abundance 158:166 arg1 The 154:156 The 154:156 The 154:156 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 5 3 dep % 1182:1182 arg1 to 1175:1176 to 1175:1176 to 1175:1176 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 1 4 theme products 377:384 arg1 color 364:368 color 364:368 color 364:368 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 1 4 theme products 377:384 arg1 odor 355:358 undesired odor 345:358 undesired odor 345:358 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 1 5 theme dissolved 196:204 arg1 matter 214:219 dissolved organic matter 196:219 dissolved organic matter (DOM) 196:225 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 1 5 theme dissolved 196:204 arg1 DOM 222:224 DOM 222:224 DOM 222:224 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 2 6 theme multiple 501:508 arg1 techniques 533:542 multiple complementary analysis techniques 501:542 multiple complementary analysis techniques 501:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 0 7 theme Magnetic 114:121 arg1 Resonance 123:131 Nuclear Magnetic Resonance 106:131 Nuclear Magnetic Resonance 106:131 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 6 8 theme photo-induced 1430:1442 arg1 transformations 1448:1462 photo-induced DOM transformations 1430:1462 photo-induced DOM transformations 1430:1462 The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. 35897429 1 9 theme matter 214:219 arg1 abundance 158:166 abundance 158:166 abundance 158:166 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 1 9 theme matter 214:219 arg1 composition 181:191 chemical composition 172:191 chemical composition 172:191 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 2 10 from changes 445:451 arg1 ponds 469:473 solar ponds 463:473 solar ponds from Salt Lake brine with multiple complementary analysis techniques 463:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 2 10 from changes 445:451 arg1 brine 490:494 Salt Lake brine 480:494 Salt Lake brine with multiple complementary analysis techniques 480:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 5 11 theme solar 1021:1025 arg1 process 1032:1038 the solar pond process 1017:1038 the solar pond process 1017:1038 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 8 12 theme chemical 1701:1708 arg1 composition 1710:1720 DOM chemical composition 1697:1720 DOM chemical composition 1697:1720 Our results here provide new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine. 35897429 4 13 theme Salt 847:850 arg1 brine 857:861 Salt Lake brine 847:861 Salt Lake brine 847:861 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 2 14 theme analysis 524:531 arg1 techniques 533:542 multiple complementary analysis techniques 501:542 multiple complementary analysis techniques 501:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 5 15 theme % 1003:1003 arg1 % 1012:1012 49.5% to 59.2% 999:1012 49.5% to 59.2% in the solar pond process 999:1038 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 5 16 theme Further 864:870 arg1 analyses 884:891 Further qualitative analyses 864:891 Further qualitative analyses 864:891 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 7 17 theme polysaccharides 1538:1552 arg1 abundance 1525:1533 the abundance 1521:1533 the abundance of polysaccharides 1521:1552 In the Salt Lake brine, exposure-driven decay decreased the abundance of polysaccharides and increased that of mono- and polyaromatic pyrolysis products. 35897429 4 18 theme brine 857:861 arg1 evaporation/irradiation 820:842 evaporation/irradiation 820:842 evaporation/irradiation of Salt Lake brine 820:861 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 8 19 theme solar 1729:1733 arg1 ponds 1735:1739 the solar ponds 1725:1739 the solar ponds of Salt Lake brine 1725:1758 Our results here provide new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine. 35897429 5 20 from % 1012:1012 arg1 process 1032:1038 the solar pond process 1017:1038 the solar pond process 1017:1038 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 2 21 theme complementary 510:522 arg1 techniques 533:542 multiple complementary analysis techniques 501:542 multiple complementary analysis techniques 501:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 1 22 theme brine 328:332 arg1 rates 315:319 mineral extraction and evaporation rates 280:319 mineral extraction and evaporation rates of the brine 280:332 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 1 23 from abundance 158:166 arg1 ponds 249:253 solar ponds 243:253 solar ponds 243:253 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 7 24 theme exposure-driven 1489:1503 arg1 decay 1505:1509 exposure-driven decay 1489:1509 exposure-driven decay 1489:1509 In the Salt Lake brine, exposure-driven decay decreased the abundance of polysaccharides and increased that of mono- and polyaromatic pyrolysis products. 35897429 2 25 theme Salt 480:483 arg1 brine 490:494 Salt Lake brine 480:494 Salt Lake brine with multiple complementary analysis techniques 480:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 0 26 from Characterization 0:15 arg1 Ponds 54:58 Solar Ponds 48:58 Solar Ponds 48:58 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 4 27 theme solar 731:735 arg1 ponds 737:741 solar ponds 731:741 solar ponds 731:741 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 0 28 theme Infrared 83:90 arg1 Spectroscopy 92:103 Infrared Spectroscopy 83:103 Infrared Spectroscopy 83:103 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 2 29 dep composition 429:439 arg1 the 425:427 the 425:427 the 425:427 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 6 30 theme pyrolysis-gas 1219:1231 arg1 spectrometry 1253:1264 pyrolysis-gas chromatography-mass spectrometry 1219:1264 The pyrolysis-gas chromatography-mass spectrometry results 1215:1272 The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. 35897429 1 31 theme undesired 345:353 arg1 odor 355:358 undesired odor 345:358 undesired odor 345:358 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 5 32 theme compounds 942:950 arg1 abundance 919:927 the relative abundance 906:927 the relative abundance of aliphatic compounds (including functionalized ones) 906:982 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 0 33 from Matter 38:43 arg1 Ponds 54:58 Solar Ponds 48:58 Solar Ponds 48:58 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 4 34 theme dissolved 703:711 arg1 carbon 721:726 dissolved organic carbon 703:726 dissolved organic carbon 703:726 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 6 35 theme anaerobic 1347:1355 arg1 decay 1364:1368 some anaerobic biotic decay 1342:1368 some anaerobic biotic decay 1342:1368 The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. 35897429 8 36 theme Lake 1749:1752 arg1 brine 1754:1758 Salt Lake brine 1744:1758 Salt Lake brine 1744:1758 Our results here provide new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine. 35897429 4 37 theme carbon 721:726 arg1 concentrations 685:698 The concentrations 681:698 The concentrations of dissolved organic carbon in solar ponds 681:741 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 0 38 theme Dissolved 20:28 arg1 Matter 38:43 Dissolved Organic Matter 20:43 Dissolved Organic Matter in Solar Ponds 20:58 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 5 39 theme relative 910:917 arg1 abundance 919:927 the relative abundance 906:927 the relative abundance of aliphatic compounds (including functionalized ones) 906:982 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 7 40 theme polyaromatic 1586:1597 arg1 products 1609:1616 polyaromatic pyrolysis products 1586:1616 polyaromatic pyrolysis products 1586:1616 In the Salt Lake brine, exposure-driven decay decreased the abundance of polysaccharides and increased that of mono- and polyaromatic pyrolysis products. 35897429 6 41 theme sulfur-containing 1307:1323 arg1 organics 1325:1332 some sulfur-containing organics 1302:1332 some sulfur-containing organics 1302:1332 The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. 35897429 1 42 theme extraction 288:297 arg1 rates 315:319 mineral extraction and evaporation rates 280:319 mineral extraction and evaporation rates of the brine 280:332 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 0 43 theme Matter 38:43 arg1 Characterization 0:15 Characterization 0:15 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 0:152 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 5 44 theme carboxylic 1077:1086 arg1 moieties 1093:1100 carboxylic acid moieties 1077:1100 carboxylic acid moieties 1077:1100 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 3 45 theme Lake 595:598 arg1 brine 600:604 Salt Lake brine 590:604 Salt Lake brine 590:604 The results showed that the DOM derived from Salt Lake brine was primarily composed of carbohydrates, aliphatic and aromatic compounds. 35897429 0 46 theme Solar 48:52 arg1 Ponds 54:58 Solar Ponds 48:58 Solar Ponds 48:58 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 1 47 theme evaporation 303:313 arg1 rates 315:319 mineral extraction and evaporation rates 280:319 mineral extraction and evaporation rates of the brine 280:332 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 4 48 theme exposure 758:765 arg1 time 767:770 exposure time 758:770 exposure time 758:770 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 3 49 theme aromatic 661:668 arg1 compounds 670:678 aliphatic and aromatic compounds 647:678 aliphatic and aromatic compounds 647:678 The results showed that the DOM derived from Salt Lake brine was primarily composed of carbohydrates, aliphatic and aromatic compounds. 35897429 3 49 theme aromatic 661:668 arg1 carbohydrates 632:644 carbohydrates 632:644 carbohydrates 632:644 The results showed that the DOM derived from Salt Lake brine was primarily composed of carbohydrates, aliphatic and aromatic compounds. 35897429 5 50 dep % 1012:1012 arg1 to 1005:1006 to 1005:1006 to 1005:1006 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 3 51 theme aliphatic 647:655 arg1 compounds 670:678 aliphatic and aromatic compounds 647:678 aliphatic and aromatic compounds 647:678 The results showed that the DOM derived from Salt Lake brine was primarily composed of carbohydrates, aliphatic and aromatic compounds. 35897429 3 51 theme aliphatic 647:655 arg1 carbohydrates 632:644 carbohydrates 632:644 carbohydrates 632:644 The results showed that the DOM derived from Salt Lake brine was primarily composed of carbohydrates, aliphatic and aromatic compounds. 35897429 8 52 theme new 1644:1646 arg1 insights 1648:1655 new insights 1644:1655 new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine 1644:1758 Our results here provide new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine. 35897429 1 53 theme chemical 172:179 arg1 composition 181:191 chemical composition 172:191 chemical composition 172:191 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 6 54 theme DOM 1444:1446 arg1 transformations 1448:1462 photo-induced DOM transformations 1430:1462 photo-induced DOM transformations 1430:1462 The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. 35897429 1 55 theme organic 206:212 arg1 matter 214:219 dissolved organic matter 196:219 dissolved organic matter (DOM) 196:225 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 1 55 theme organic 206:212 arg1 DOM 222:224 DOM 222:224 DOM 222:224 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 4 56 from concentrations 685:698 arg1 ponds 737:741 solar ponds 731:741 solar ponds 731:741 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 2 57 theme Lake 485:488 arg1 brine 490:494 Salt Lake brine 480:494 Salt Lake brine with multiple complementary analysis techniques 480:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 5 58 theme pond 1027:1030 arg1 process 1032:1038 the solar pond process 1017:1038 the solar pond process 1017:1038 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 8 59 theme DOM 1697:1699 arg1 composition 1710:1720 DOM chemical composition 1697:1720 DOM chemical composition 1697:1720 Our results here provide new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine. 35897429 1 60 dep ponds 249:253 arg1 the 230:232 the 230:232 the 230:232 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 1 60 dep ponds 249:253 arg1 brine 234:238 brine 234:238 brine 234:238 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 5 61 dep compounds 942:950 arg1 including 953:961 including 953:961 including functionalized ones 953:981 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 8 62 theme composition 1710:1720 arg1 changes 1686:1692 the changes 1682:1692 the changes of DOM chemical composition in the solar ponds of Salt Lake brine 1682:1758 Our results here provide new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine. 35897429 5 63 theme qualitative 872:882 arg1 analyses 884:891 Further qualitative analyses 864:891 Further qualitative analyses 864:891 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 3 64 attach derived 577:583 arg1 brine 600:604 Salt Lake brine 590:604 Salt Lake brine 590:604 The results showed that the DOM derived from Salt Lake brine was primarily composed of carbohydrates, aliphatic and aromatic compounds. 35897429 3 64 attach derived 577:583 arg2 DOM 573:575 the DOM 569:575 the DOM derived from Salt Lake brine 569:604 The results showed that the DOM derived from Salt Lake brine was primarily composed of carbohydrates, aliphatic and aromatic compounds. 35897429 4 65 theme Lake 852:855 arg1 brine 857:861 Salt Lake brine 847:861 Salt Lake brine 847:861 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 0 66 theme Elemental 63:71 arg1 Analysis 73:80 Elemental Analysis 63:80 Elemental Analysis 63:80 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 4 67 dep increased 743:751 arg1 mg/L 809:812 23.4 to 330.8 mg/L 795:812 23.4 to 330.8 mg/L 795:812 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 2 68 theme DOM 456:458 arg1 changes 445:451 changes 445:451 changes 445:451 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 2 68 theme DOM 456:458 arg1 composition 429:439 composition 429:439 composition 429:439 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 6 69 theme spectrometry 1253:1264 arg1 results 1266:1272 The pyrolysis-gas chromatography-mass spectrometry results 1215:1272 The pyrolysis-gas chromatography-mass spectrometry results 1215:1272 The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. 35897429 1 70 from composition 181:191 arg1 ponds 249:253 solar ponds 243:253 solar ponds 243:253 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 5 71 theme % 1173:1173 arg1 % 1182:1182 26.1% to 13.4% 1169:1182 26.1% to 13.4% 1169:1182 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 8 72 theme Salt 1744:1747 arg1 brine 1754:1758 Salt Lake brine 1744:1758 Salt Lake brine 1744:1758 Our results here provide new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine. 35897429 7 73 theme Lake 1477:1480 arg1 brine 1482:1486 the Salt Lake brine 1468:1486 the Salt Lake brine 1468:1486 In the Salt Lake brine, exposure-driven decay decreased the abundance of polysaccharides and increased that of mono- and polyaromatic pyrolysis products. 35897429 0 74 from Ponds 54:58 arg1 Characterization 0:15 Characterization 0:15 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 0:152 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 0 75 theme Nuclear 106:112 arg1 Resonance 123:131 Nuclear Magnetic Resonance 106:131 Nuclear Magnetic Resonance 106:131 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 4 76 dep 15-fold 781:787 arg1 to 778:779 to 778:779 to 778:779 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 5 77 theme aliphatic 932:940 arg1 compounds 942:950 aliphatic compounds 932:950 aliphatic compounds (including functionalized ones) 932:982 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 2 78 theme solar 463:467 arg1 ponds 469:473 solar ponds 463:473 solar ponds from Salt Lake brine with multiple complementary analysis techniques 463:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 6 79 theme chromatography-mass 1233:1251 arg1 spectrometry 1253:1264 pyrolysis-gas chromatography-mass spectrometry 1219:1264 The pyrolysis-gas chromatography-mass spectrometry results 1215:1272 The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. 35897429 4 80 dep 330.8 803:807 arg1 to 800:801 to 800:801 to 800:801 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 0 81 theme Organic 30:36 arg1 Matter 38:43 Dissolved Organic Matter 20:43 Dissolved Organic Matter in Solar Ponds 20:58 Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS. 35897429 8 82 theme brine 1754:1758 arg1 ponds 1735:1739 the solar ponds 1725:1739 the solar ponds of Salt Lake brine 1725:1758 Our results here provide new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine. 35897429 4 83 theme organic 713:719 arg1 carbon 721:726 dissolved organic carbon 703:726 dissolved organic carbon 703:726 The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. 35897429 6 84 theme organics 1325:1332 arg1 presence 1290:1297 the presence 1286:1297 the presence of some sulfur-containing organics 1286:1332 The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. 35897429 1 85 theme mineral 280:286 arg1 extraction 288:297 mineral extraction 280:297 mineral extraction 280:297 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 7 86 theme Salt 1472:1475 arg1 brine 1482:1486 the Salt Lake brine 1468:1486 the Salt Lake brine 1468:1486 In the Salt Lake brine, exposure-driven decay decreased the abundance of polysaccharides and increased that of mono- and polyaromatic pyrolysis products. 35897429 7 87 theme pyrolysis 1599:1607 arg1 products 1609:1616 polyaromatic pyrolysis products 1586:1616 polyaromatic pyrolysis products 1586:1616 In the Salt Lake brine, exposure-driven decay decreased the abundance of polysaccharides and increased that of mono- and polyaromatic pyrolysis products. 35897429 3 88 theme Salt 590:593 arg1 brine 600:604 Salt Lake brine 590:604 Salt Lake brine 590:604 The results showed that the DOM derived from Salt Lake brine was primarily composed of carbohydrates, aliphatic and aromatic compounds. 35897429 5 89 theme acid 1088:1091 arg1 moieties 1093:1100 carboxylic acid moieties 1077:1100 carboxylic acid moieties 1077:1100 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 2 90 with brine 490:494 arg1 techniques 533:542 multiple complementary analysis techniques 501:542 multiple complementary analysis techniques 501:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 1 91 theme rates 315:319 arg1 efficiency 266:275 the efficiency 262:275 the efficiency of mineral extraction and evaporation rates of the brine 262:332 The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. 35897429 2 92 from brine 490:494 arg1 ponds 469:473 solar ponds 463:473 solar ponds from Salt Lake brine with multiple complementary analysis techniques 463:542 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 2 92 from brine 490:494 arg1 changes 445:451 changes 445:451 changes 445:451 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 2 92 from brine 490:494 arg1 composition 429:439 composition 429:439 composition 429:439 Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. 35897429 8 93 from changes 1686:1692 arg1 ponds 1735:1739 the solar ponds 1725:1739 the solar ponds of Salt Lake brine 1725:1758 Our results here provide new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine. 35897429 5 94 theme functionalized 963:976 arg1 ones 978:981 functionalized ones 963:981 functionalized ones 963:981 Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. 35897429 6 95 theme biotic 1357:1362 arg1 decay 1364:1368 some anaerobic biotic decay 1342:1368 some anaerobic biotic decay 1342:1368 The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. 35897429 6 96 theme microbiological 1375:1389 arg1 processes 1391:1399 microbiological processes 1375:1399 microbiological processes 1375:1399 The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. 36759532 4 0 theme different 946:954 arg1 stimuli 967:973 different electrical stimuli 946:973 different electrical stimuli 946:973 Under different electrical stimuli, each component changed significantly (P < 0.05). 36759532 5 1 theme nitrogen 1077:1084 arg1 contents 1101:1108 total nitrogen and phosphorus contents 1071:1108 total nitrogen and phosphorus contents 1071:1108 pH and conductivity were higher at 6 V 20 mA, total nitrogen and phosphorus contents reached their maximum at 5 V 30 mA, and total potassium at 6 V 10 mA. 36759532 2 2 theme electrical 576:585 arg1 stimulation 587:597 the best electrical stimulation 567:597 the best electrical stimulation group 567:603 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 7 3 theme 5 V 1471:1473 arg1 10 mA 1475:1479 5 V 10 mA 1471:1479 5 V 10 mA 1471:1479 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 1 4 theme soil 261:264 arg1 remediation 266:276 contaminated soil remediation 248:276 contaminated soil remediation 248:276 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 36759532 0 5 theme electrical 88:97 arg1 stimuli 99:105 different electrical stimuli 78:105 different electrical stimuli 78:105 Compositional changes and ecological characteristics of earthworm mucus under different electrical stimuli. 36759532 2 6 theme best 571:574 arg1 stimulation 587:597 the best electrical stimulation 567:597 the best electrical stimulation group 567:603 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 2 7 theme soil 638:641 arg1 pollution 655:663 soil heavy metal pollution remediation and sludge reutilization 638:700 soil heavy metal pollution remediation and sludge reutilization 638:700 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 5 8 theme total 1150:1154 arg1 potassium 1156:1164 total potassium 1150:1164 total potassium 1150:1164 pH and conductivity were higher at 6 V 20 mA, total nitrogen and phosphorus contents reached their maximum at 5 V 30 mA, and total potassium at 6 V 10 mA. 36759532 2 9 theme mucus 501:505 arg1 changes 486:492 the compositional changes 468:492 the compositional changes of the mucus produced under different electrical stimuli 468:549 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 5 10 theme phosphorus 1090:1099 arg1 contents 1101:1108 total nitrogen and phosphorus contents 1071:1108 total nitrogen and phosphorus contents 1071:1108 pH and conductivity were higher at 6 V 20 mA, total nitrogen and phosphorus contents reached their maximum at 5 V 30 mA, and total potassium at 6 V 10 mA. 36759532 6 11 theme trace 1281:1285 arg1 elements 1293:1300 trace metal elements 1281:1300 trace metal elements 1281:1300 Protein, amino acids, and carbohydrates were most abundant in the mucus produced at 5 V 10 mA, while trace metal elements reached their lowest values at 5 V 10 mA. 36759532 7 12 theme component 1372:1380 arg1 analysis 1382:1389 principal component analysis 1362:1389 principal component analysis 1362:1389 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 7 13 from acids 1516:1520 arg1 high 1502:1505 high 1502:1505 high 1502:1505 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 2 14 theme applicable 624:633 arg1 group 599:603 the best electrical stimulation group 567:603 the best electrical stimulation group 567:603 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 3 15 theme small 876:880 arg1 alcohol 893:899 alcohol 893:899 alcohol 893:899 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 15 theme small 876:880 arg1 amounts 882:888 small amounts 876:888 small amounts of alcohol, phenol, and ester organic substances 876:937 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 15 theme small 876:880 arg1 substances 928:937 ester organic substances 914:937 ester organic substances 914:937 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 15 theme small 876:880 arg1 phenol 902:907 phenol 902:907 phenol 902:907 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 1 16 theme sludge 282:287 arg1 reutilization 289:301 sludge reutilization 282:301 sludge reutilization 282:301 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 36759532 5 17 theme 6 V 1060:1062 arg1 20 mA 1064:1068 6 V 20 mA 1060:1068 6 V 20 mA 1060:1068 pH and conductivity were higher at 6 V 20 mA, total nitrogen and phosphorus contents reached their maximum at 5 V 30 mA, and total potassium at 6 V 10 mA. 36759532 2 18 theme mucus 609:613 arg1 fraction 615:622 mucus fraction 609:622 mucus fraction 609:622 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 7 19 with combined 1395:1402 arg1 studies 1418:1424 previous studies 1409:1424 previous studies 1409:1424 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 7 20 theme suitable 1578:1585 arg1 experiments 1619:1629 most suitable for sludge and straw composting experiments 1573:1629 most suitable for sludge and straw composting experiments 1573:1629 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 7 21 from elements 1559:1566 arg1 low 1540:1542 low 1540:1542 low 1540:1542 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 7 22 theme previous 1409:1416 arg1 studies 1418:1424 previous studies 1409:1424 previous studies 1409:1424 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 3 23 theme amino 809:813 arg1 acids 815:819 amino acids 809:819 amino acids 809:819 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 1 24 from nutrients 135:143 arg1 rich 127:130 rich 127:130 rich 127:130 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 36759532 7 25 theme high 1502:1505 arg1 alkaline 1492:1499 alkaline 1492:1499 alkaline 1492:1499 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 7 25 theme high 1502:1505 arg1 mucus 1453:1457 the mucus 1449:1457 the mucus produced at 5 V 10 mA 1449:1479 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 7 26 theme principal 1362:1370 arg1 analysis 1382:1389 principal component analysis 1362:1389 principal component analysis 1362:1389 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 4 27 dep changed 991:997 arg1 P < 0.05 1014:1021 P < 0.05 1014:1021 P < 0.05 1014:1021 Under different electrical stimuli, each component changed significantly (P < 0.05). 36759532 2 28 theme compositional 472:484 arg1 changes 486:492 the compositional changes 468:492 the compositional changes of the mucus produced under different electrical stimuli 468:549 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 2 29 theme voltage 323:329 arg1 combinations 343:354 six voltage and current combinations 319:354 six voltage and current combinations 319:354 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 0 30 theme Compositional 0:12 arg1 changes 14:20 Compositional changes 0:20 Compositional changes 0:20 Compositional changes and ecological characteristics of earthworm mucus under different electrical stimuli. 36759532 2 31 theme stimulation 587:597 arg1 group 599:603 the best electrical stimulation group 567:603 the best electrical stimulation group 567:603 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 1 32 from rich 127:130 arg1 nutrients 135:143 nutrients 135:143 nutrients that can initiate the mineralization and humification of organic matter 135:215 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 36759532 1 33 dep mineralization 167:180 arg1 the 163:165 the 163:165 the 163:165 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 36759532 2 34 dep 20 428:429 arg1 10 424:425 10 424:425 10 424:425 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 2 35 theme mucus 391:395 arg1 production 397:406 earthworm mucus production 381:406 earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively) 381:454 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 0 36 theme ecological 26:35 arg1 characteristics 37:51 ecological characteristics 26:51 ecological characteristics 26:51 Compositional changes and ecological characteristics of earthworm mucus under different electrical stimuli. 36759532 2 37 theme metal 649:653 arg1 pollution 655:663 soil heavy metal pollution remediation and sludge reutilization 638:700 soil heavy metal pollution remediation and sludge reutilization 638:700 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 2 38 theme electrical 532:541 arg1 stimuli 543:549 different electrical stimuli 522:549 different electrical stimuli 522:549 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 2 39 theme heavy 643:647 arg1 pollution 655:663 soil heavy metal pollution remediation and sludge reutilization 638:700 soil heavy metal pollution remediation and sludge reutilization 638:700 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 2 40 used utilized 361:368 arg2 combinations 343:354 six voltage and current combinations 319:354 six voltage and current combinations 319:354 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 1 41 theme matter 210:215 arg1 humification 186:197 humification 186:197 humification 186:197 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 36759532 1 41 theme matter 210:215 arg1 mineralization 167:180 mineralization 167:180 mineralization 167:180 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 36759532 1 42 theme Earthworm 108:116 arg1 mucus 118:122 Earthworm mucus 108:122 Earthworm mucus 108:122 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 36759532 2 43 theme different 522:530 arg1 stimuli 543:549 different electrical stimuli 522:549 different electrical stimuli 522:549 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 3 44 theme alcohol 893:899 arg1 alcohol 893:899 alcohol 893:899 alcohol 893:899 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 44 theme alcohol 893:899 arg1 amounts 882:888 small amounts 876:888 small amounts of alcohol, phenol, and ester organic substances 876:937 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 44 theme alcohol 893:899 arg1 substances 928:937 ester organic substances 914:937 ester organic substances 914:937 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 44 theme alcohol 893:899 arg1 phenol 902:907 phenol 902:907 phenol 902:907 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 7 45 theme metal 1553:1557 arg1 elements 1559:1566 trace metal elements 1547:1566 trace metal elements 1547:1566 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 6 46 theme 5 V 1264:1266 arg1 10 mA 1268:1272 5 V 10 mA 1264:1272 5 V 10 mA 1264:1272 Protein, amino acids, and carbohydrates were most abundant in the mucus produced at 5 V 10 mA, while trace metal elements reached their lowest values at 5 V 10 mA. 36759532 7 47 theme low 1540:1542 arg1 alkaline 1492:1499 alkaline 1492:1499 alkaline 1492:1499 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 7 47 theme low 1540:1542 arg1 mucus 1453:1457 the mucus 1449:1457 the mucus produced at 5 V 10 mA 1449:1479 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 1 48 theme organic 202:208 arg1 matter 210:215 organic matter 202:215 organic matter 202:215 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 36759532 4 49 theme electrical 956:965 arg1 stimuli 967:973 different electrical stimuli 946:973 different electrical stimuli 946:973 Under different electrical stimuli, each component changed significantly (P < 0.05). 36759532 3 50 theme electrical 757:766 arg1 stimuli 768:774 the six electrical stimuli 749:774 the six electrical stimuli 749:774 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 51 theme ester 914:918 arg1 substances 928:937 ester organic substances 914:937 ester organic substances 914:937 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 0 52 theme mucus 66:70 arg1 changes 14:20 Compositional changes 0:20 Compositional changes 0:20 Compositional changes and ecological characteristics of earthworm mucus under different electrical stimuli. 36759532 0 52 theme mucus 66:70 arg1 characteristics 37:51 ecological characteristics 26:51 ecological characteristics 26:51 Compositional changes and ecological characteristics of earthworm mucus under different electrical stimuli. 36759532 6 53 theme metal 1287:1291 arg1 elements 1293:1300 trace metal elements 1281:1300 trace metal elements 1281:1300 Protein, amino acids, and carbohydrates were most abundant in the mucus produced at 5 V 10 mA, while trace metal elements reached their lowest values at 5 V 10 mA. 36759532 5 54 theme 5 V 1135:1137 arg1 30 mA 1139:1143 5 V 30 mA 1135:1143 5 V 30 mA 1135:1143 pH and conductivity were higher at 6 V 20 mA, total nitrogen and phosphorus contents reached their maximum at 5 V 30 mA, and total potassium at 6 V 10 mA. 36759532 3 55 theme organic 920:926 arg1 substances 928:937 ester organic substances 914:937 ester organic substances 914:937 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 6 56 from abundant 1230:1237 arg1 mucus 1246:1250 the mucus 1242:1250 the mucus produced at 5 V 10 mA 1242:1272 Protein, amino acids, and carbohydrates were most abundant in the mucus produced at 5 V 10 mA, while trace metal elements reached their lowest values at 5 V 10 mA. 36759532 0 57 theme earthworm 56:64 arg1 mucus 66:70 earthworm mucus 56:70 earthworm mucus 56:70 Compositional changes and ecological characteristics of earthworm mucus under different electrical stimuli. 36759532 6 58 from mucus 1246:1250 arg1 abundant 1230:1237 abundant 1230:1237 abundant 1230:1237 Protein, amino acids, and carbohydrates were most abundant in the mucus produced at 5 V 10 mA, while trace metal elements reached their lowest values at 5 V 10 mA. 36759532 7 59 theme soil 1632:1635 arg1 remediation 1637:1647 soil remediation 1632:1647 soil remediation 1632:1647 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 7 60 from nutrients 1526:1534 arg1 high 1502:1505 high 1502:1505 high 1502:1505 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 2 61 theme sludge 681:686 arg1 reutilization 688:700 sludge reutilization 681:700 sludge reutilization 681:700 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 7 62 theme amendment 1653:1661 arg1 experiments 1663:1673 amendment experiments 1653:1673 amendment experiments 1653:1673 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 2 63 dep production 397:406 arg1 30 mA 435:439 6 V at 10, 20 and 30 mA 417:439 6 V at 10, 20 and 30 mA 417:439 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 2 63 dep production 397:406 arg1 5 V 409:411 5 V 409:411 5 V 409:411 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 6 64 theme amino 1189:1193 arg1 acids 1195:1199 amino acids 1189:1199 amino acids 1189:1199 Protein, amino acids, and carbohydrates were most abundant in the mucus produced at 5 V 10 mA, while trace metal elements reached their lowest values at 5 V 10 mA. 36759532 2 65 theme current 335:341 arg1 combinations 343:354 six voltage and current combinations 319:354 six voltage and current combinations 319:354 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 3 66 theme fatty 837:841 arg1 acids 843:847 fatty acids 837:847 fatty acids 837:847 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 1 67 theme great 227:231 arg1 importance 233:242 great importance 227:242 great importance 227:242 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 36759532 7 68 from low 1540:1542 arg1 elements 1559:1566 trace metal elements 1547:1566 trace metal elements 1547:1566 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 6 69 theme lowest 1316:1321 arg1 values 1323:1328 their lowest values 1310:1328 their lowest values 1310:1328 Protein, amino acids, and carbohydrates were most abundant in the mucus produced at 5 V 10 mA, while trace metal elements reached their lowest values at 5 V 10 mA. 36759532 7 70 theme trace 1547:1551 arg1 elements 1559:1566 trace metal elements 1547:1566 trace metal elements 1547:1566 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 3 71 theme phenol 902:907 arg1 alcohol 893:899 alcohol 893:899 alcohol 893:899 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 71 theme phenol 902:907 arg1 amounts 882:888 small amounts 876:888 small amounts of alcohol, phenol, and ester organic substances 876:937 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 71 theme phenol 902:907 arg1 substances 928:937 ester organic substances 914:937 ester organic substances 914:937 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 71 theme phenol 902:907 arg1 phenol 902:907 phenol 902:907 phenol 902:907 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 7 72 theme composting 1608:1617 arg1 experiments 1619:1629 most suitable for sludge and straw composting experiments 1573:1629 most suitable for sludge and straw composting experiments 1573:1629 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 0 73 theme different 78:86 arg1 stimuli 99:105 different electrical stimuli 78:105 different electrical stimuli 78:105 Compositional changes and ecological characteristics of earthworm mucus under different electrical stimuli. 36759532 7 74 from high 1502:1505 arg1 nutrients 1526:1534 nutrients 1526:1534 nutrients 1526:1534 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 7 74 from high 1502:1505 arg1 acids 1516:1520 amino acids 1510:1520 amino acids 1510:1520 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 2 75 theme earthworm 381:389 arg1 production 397:406 earthworm mucus production 381:406 earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively) 381:454 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 2 76 dep pollution 655:663 arg1 reutilization 688:700 sludge reutilization 681:700 sludge reutilization 681:700 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 2 76 dep pollution 655:663 arg1 remediation 665:675 remediation 665:675 remediation 665:675 In this study, six voltage and current combinations were utilized to promote earthworm mucus production (5 V and 6 V at 10, 20 and 30 mA, respectively), to explore the compositional changes of the mucus produced under different electrical stimuli, and to propose the best electrical stimulation group and mucus fraction applicable to soil heavy metal pollution remediation and sludge reutilization. 36759532 5 77 theme total 1071:1075 arg1 contents 1101:1108 total nitrogen and phosphorus contents 1071:1108 total nitrogen and phosphorus contents 1071:1108 pH and conductivity were higher at 6 V 20 mA, total nitrogen and phosphorus contents reached their maximum at 5 V 30 mA, and total potassium at 6 V 10 mA. 36759532 3 78 theme substances 928:937 arg1 alcohol 893:899 alcohol 893:899 alcohol 893:899 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 78 theme substances 928:937 arg1 amounts 882:888 small amounts 876:888 small amounts of alcohol, phenol, and ester organic substances 876:937 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 78 theme substances 928:937 arg1 substances 928:937 ester organic substances 914:937 ester organic substances 914:937 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 3 78 theme substances 928:937 arg1 phenol 902:907 phenol 902:907 phenol 902:907 The results showed that the mucus produced by the six electrical stimuli was mainly composed of proteins, amino acids, carbohydrates, fatty acids, and polysaccharides, with small amounts of alcohol, phenol, and ester organic substances. 36759532 5 79 theme 6 V 1169:1171 arg1 10 mA 1173:1177 6 V 10 mA 1169:1177 6 V 10 mA 1169:1177 pH and conductivity were higher at 6 V 20 mA, total nitrogen and phosphorus contents reached their maximum at 5 V 30 mA, and total potassium at 6 V 10 mA. 36759532 7 80 theme amino 1510:1514 arg1 acids 1516:1520 amino acids 1510:1520 amino acids 1510:1520 Finally, based on principal component analysis and combined with previous studies, it was concluded that the mucus produced at 5 V 10 mA was weakly alkaline, high in amino acids and nutrients and low in trace metal elements, and most suitable for sludge and straw composting experiments, soil remediation and amendment experiments. 36759532 1 81 theme contaminated 248:259 arg1 remediation 266:276 contaminated soil remediation 248:276 contaminated soil remediation 248:276 Earthworm mucus is rich in nutrients that can initiate the mineralization and humification of organic matter and is of great importance for contaminated soil remediation and sludge reutilization. 35306147 8 0 theme N-linked 1098:1105 arg1 present 1122:1128 the N-linked galactomannans present 1094:1128 the N-linked galactomannans present on secreted glycoproteins 1094:1154 DFG-5 is able to discriminate between cell wall and secreted glycoproteins, and does not bind to the N-linked galactomannans present on secreted glycoproteins. 35306147 3 1 theme wall 469:472 arg1 glycoproteins 474:486 cell wall glycoproteins 464:486 cell wall glycoproteins 464:486 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 6 2 theme enzyme 855:860 arg1 function 862:869 enzyme function 855:869 enzyme function 855:869 D76 and E130, which are located in a groove on the opposite side of the protein, are also important for enzyme function. 35306147 5 3 theme Site-directed 631:643 arg1 mutagenesis 645:655 Site-directed mutagenesis 631:655 Site-directed mutagenesis 631:655 Site-directed mutagenesis and complementation experiments show that D116 and D117 are located at the DFG-5 active site. 35306147 8 4 gly glycoproteins 1142:1154 arg1 glycoproteins 1142:1154 secreted glycoproteins 1133:1154 secreted glycoproteins 1133:1154 DFG-5 is able to discriminate between cell wall and secreted glycoproteins, and does not bind to the N-linked galactomannans present on secreted glycoproteins. 35306147 10 5 theme cell 1329:1332 arg1 incorporation 1339:1351 cell wall incorporation 1329:1351 cell wall incorporation by lichenin transferases 1329:1376 By processing the galactomannans on cell wall proteins, DFG-5 targets them for cell wall incorporation by lichenin transferases. 35306147 9 6 theme key 1171:1173 arg1 role 1175:1178 a key role 1169:1178 a key role 1169:1178 DFG-5 plays a key role in targeting extracellular glycoproteins to their final destinations. 35306147 10 7 theme wall 1334:1337 arg1 incorporation 1339:1351 cell wall incorporation 1329:1351 cell wall incorporation by lichenin transferases 1329:1376 By processing the galactomannans on cell wall proteins, DFG-5 targets them for cell wall incorporation by lichenin transferases. 35306147 2 8 theme important 251:259 arg1 role 261:264 an important role 248:264 an important role 248:264 Fungi express members of the GH76 family of α-1,6-mannanases which play an important role in cell wall biogenesis. 35306147 8 9 link N-linked 1098:1105 arg1 present 1122:1128 the N-linked galactomannans present 1094:1128 the N-linked galactomannans present on secreted glycoproteins 1094:1154 DFG-5 is able to discriminate between cell wall and secreted glycoproteins, and does not bind to the N-linked galactomannans present on secreted glycoproteins. 35306147 6 10 located located 775:781 arg2 D76 751:753 D76 751:753 D76 751:753 D76 and E130, which are located in a groove on the opposite side of the protein, are also important for enzyme function. 35306147 6 10 located located 775:781 arg1 groove 788:793 a groove 786:793 a groove on the opposite side of the protein 786:829 D76 and E130, which are located in a groove on the opposite side of the protein, are also important for enzyme function. 35306147 6 10 located located 775:781 arg2 E130 759:762 E130 759:762 E130 759:762 D76 and E130, which are located in a groove on the opposite side of the protein, are also important for enzyme function. 35306147 8 11 theme galactomannans 1107:1120 arg1 present 1122:1128 the N-linked galactomannans present 1094:1128 the N-linked galactomannans present on secreted glycoproteins 1094:1154 DFG-5 is able to discriminate between cell wall and secreted glycoproteins, and does not bind to the N-linked galactomannans present on secreted glycoproteins. 35306147 3 12 link N-linked 432:439 arg1 galactomannan 441:453 an N-linked galactomannan 429:453 an N-linked galactomannan found on cell wall glycoproteins 429:486 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 10 13 theme lichenin 1356:1363 arg1 transferases 1365:1376 lichenin transferases 1356:1376 lichenin transferases 1356:1376 By processing the galactomannans on cell wall proteins, DFG-5 targets them for cell wall incorporation by lichenin transferases. 35306147 0 14 gly glycoproteins 68:80 arg1 glycoproteins 68:80 secreted glycoproteins 59:80 secreted glycoproteins 59:80 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 35306147 8 15 theme secreted 1133:1140 arg1 glycoproteins 1142:1154 secreted glycoproteins 1133:1154 secreted glycoproteins 1133:1154 DFG-5 is able to discriminate between cell wall and secreted glycoproteins, and does not bind to the N-linked galactomannans present on secreted glycoproteins. 35306147 3 16 theme N-linked 432:439 arg1 galactomannan 441:453 an N-linked galactomannan 429:453 an N-linked galactomannan found on cell wall glycoproteins 429:486 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 3 17 gly glycoproteins 474:486 arg1 glycoproteins 474:486 cell wall glycoproteins 464:486 cell wall glycoproteins 464:486 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 6 18 from located 775:781 arg1 groove 788:793 a groove 786:793 a groove on the opposite side of the protein 786:829 D76 and E130, which are located in a groove on the opposite side of the protein, are also important for enzyme function. 35306147 5 19 theme DFG-5 732:736 arg1 site 745:748 the DFG-5 active site 728:748 the DFG-5 active site 728:748 Site-directed mutagenesis and complementation experiments show that D116 and D117 are located at the DFG-5 active site. 35306147 7 20 gly glycoproteins 882:894 arg1 glycoproteins 882:894 Cell wall glycoproteins 872:894 Cell wall glycoproteins 872:894 Cell wall glycoproteins co-purify with DFG-5 demonstrating a specific association between DFG-5 and cell wall glycoproteins. 35306147 11 21 theme secreted 1410:1417 arg1 proteins 1419:1426 secreted proteins 1410:1426 secreted proteins 1410:1426 The N-linked galactomannans on secreted proteins are not processed by DFG-5, which targets these proteins for release into the extracellular medium. 35306147 3 22 theme α-1,6-mannose 403:415 arg1 backbone 417:424 the α-1,6-mannose backbone 399:424 the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins 399:486 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 3 23 theme DFG-5 344:348 arg1 α-1,6-mannanase 350:364 the Neurospora crassa DFG-5 α-1,6-mannanase 322:364 the Neurospora crassa DFG-5 α-1,6-mannanase 322:364 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 8 24 theme cell 1035:1038 arg1 wall 1040:1043 cell wall 1035:1043 cell wall 1035:1043 DFG-5 is able to discriminate between cell wall and secreted glycoproteins, and does not bind to the N-linked galactomannans present on secreted glycoproteins. 35306147 5 25 theme active 738:743 arg1 site 745:748 the DFG-5 active site 728:748 the DFG-5 active site 728:748 Site-directed mutagenesis and complementation experiments show that D116 and D117 are located at the DFG-5 active site. 35306147 2 26 theme wall 274:277 arg1 biogenesis 279:288 cell wall biogenesis 269:288 cell wall biogenesis 269:288 Fungi express members of the GH76 family of α-1,6-mannanases which play an important role in cell wall biogenesis. 35306147 8 27 gly glycoproteins 1058:1070 arg1 glycoproteins 1058:1070 secreted glycoproteins 1049:1070 secreted glycoproteins 1049:1070 DFG-5 is able to discriminate between cell wall and secreted glycoproteins, and does not bind to the N-linked galactomannans present on secreted glycoproteins. 35306147 3 28 theme crassa 337:342 arg1 α-1,6-mannanase 350:364 the Neurospora crassa DFG-5 α-1,6-mannanase 322:364 the Neurospora crassa DFG-5 α-1,6-mannanase 322:364 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 0 29 theme Extracellular 0:12 arg1 targeting 14:22 Extracellular targeting 0:22 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 0:90 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 35306147 4 30 theme enzymatic 515:523 arg1 activity 525:532 an enzymatic activity 512:532 an enzymatic activity 512:532 We show that DFG-5 has an enzymatic activity and provide evidence that it processes the α-1,6-mannose backbone of the N-linked galactomannan. 35306147 11 31 theme N-linked 1383:1390 arg1 galactomannans 1392:1405 The N-linked galactomannans 1379:1405 The N-linked galactomannans on secreted proteins 1379:1426 The N-linked galactomannans on secreted proteins are not processed by DFG-5, which targets these proteins for release into the extracellular medium. 35306147 7 32 theme Cell 872:875 arg1 glycoproteins 882:894 Cell wall glycoproteins 872:894 Cell wall glycoproteins 872:894 Cell wall glycoproteins co-purify with DFG-5 demonstrating a specific association between DFG-5 and cell wall glycoproteins. 35306147 1 33 dep survival 138:145 arg1 the 134:136 the 134:136 the 134:136 The formation of a cell wall is vital for the survival and growth of a fungal cell. 35306147 9 34 gly glycoproteins 1207:1219 arg1 glycoproteins 1207:1219 extracellular glycoproteins 1193:1219 extracellular glycoproteins 1193:1219 DFG-5 plays a key role in targeting extracellular glycoproteins to their final destinations. 35306147 0 35 theme Neurospora 27:36 arg1 wall 50:53 Neurospora crassa cell wall 27:53 Neurospora crassa cell wall 27:53 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 35306147 7 36 theme wall 877:880 arg1 glycoproteins 882:894 Cell wall glycoproteins 872:894 Cell wall glycoproteins 872:894 Cell wall glycoproteins co-purify with DFG-5 demonstrating a specific association between DFG-5 and cell wall glycoproteins. 35306147 10 37 theme cell 1286:1289 arg1 proteins 1296:1303 cell wall proteins 1286:1303 cell wall proteins 1286:1303 By processing the galactomannans on cell wall proteins, DFG-5 targets them for cell wall incorporation by lichenin transferases. 35306147 10 38 theme wall 1291:1294 arg1 proteins 1296:1303 cell wall proteins 1286:1303 cell wall proteins 1286:1303 By processing the galactomannans on cell wall proteins, DFG-5 targets them for cell wall incorporation by lichenin transferases. 35306147 1 39 theme fungal 163:168 arg1 cell 170:173 a fungal cell 161:173 a fungal cell 161:173 The formation of a cell wall is vital for the survival and growth of a fungal cell. 35306147 2 40 theme cell 269:272 arg1 biogenesis 279:288 cell wall biogenesis 269:288 cell wall biogenesis 269:288 Fungi express members of the GH76 family of α-1,6-mannanases which play an important role in cell wall biogenesis. 35306147 6 41 theme protein 823:829 arg1 side 811:814 the opposite side 798:814 the opposite side of the protein 798:829 D76 and E130, which are located in a groove on the opposite side of the protein, are also important for enzyme function. 35306147 4 42 contain has 508:510 arg1 DFG-5 502:506 DFG-5 502:506 DFG-5 502:506 We show that DFG-5 has an enzymatic activity and provide evidence that it processes the α-1,6-mannose backbone of the N-linked galactomannan. 35306147 4 42 contain has 508:510 arg2 activity 525:532 an enzymatic activity 512:532 an enzymatic activity 512:532 We show that DFG-5 has an enzymatic activity and provide evidence that it processes the α-1,6-mannose backbone of the N-linked galactomannan. 35306147 1 43 theme cell 170:173 arg1 growth 151:156 growth 151:156 growth 151:156 The formation of a cell wall is vital for the survival and growth of a fungal cell. 35306147 1 43 theme cell 170:173 arg1 survival 138:145 survival 138:145 survival 138:145 The formation of a cell wall is vital for the survival and growth of a fungal cell. 35306147 0 44 theme cell 45:48 arg1 wall 50:53 Neurospora crassa cell wall 27:53 Neurospora crassa cell wall 27:53 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 35306147 3 45 theme cell 464:467 arg1 glycoproteins 474:486 cell wall glycoproteins 464:486 cell wall glycoproteins 464:486 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 9 46 theme extracellular 1193:1205 arg1 glycoproteins 1207:1219 extracellular glycoproteins 1193:1219 extracellular glycoproteins 1193:1219 DFG-5 plays a key role in targeting extracellular glycoproteins to their final destinations. 35306147 4 47 theme galactomannan 616:628 arg1 backbone 591:598 the α-1,6-mannose backbone 573:598 the α-1,6-mannose backbone of the N-linked galactomannan 573:628 We show that DFG-5 has an enzymatic activity and provide evidence that it processes the α-1,6-mannose backbone of the N-linked galactomannan. 35306147 0 48 theme crassa 38:43 arg1 wall 50:53 Neurospora crassa cell wall 27:53 Neurospora crassa cell wall 27:53 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 35306147 7 49 gly glycoproteins 982:994 arg1 glycoproteins 982:994 cell wall glycoproteins 972:994 cell wall glycoproteins 972:994 Cell wall glycoproteins co-purify with DFG-5 demonstrating a specific association between DFG-5 and cell wall glycoproteins. 35306147 6 50 from groove 788:793 arg1 located 775:781 located 775:781 located 775:781 D76 and E130, which are located in a groove on the opposite side of the protein, are also important for enzyme function. 35306147 6 50 from groove 788:793 arg1 side 811:814 the opposite side 798:814 the opposite side of the protein 798:829 D76 and E130, which are located in a groove on the opposite side of the protein, are also important for enzyme function. 35306147 11 51 from galactomannans 1392:1405 arg1 proteins 1419:1426 secreted proteins 1410:1426 secreted proteins 1410:1426 The N-linked galactomannans on secreted proteins are not processed by DFG-5, which targets these proteins for release into the extracellular medium. 35306147 3 52 theme Neurospora 326:335 arg1 α-1,6-mannanase 350:364 the Neurospora crassa DFG-5 α-1,6-mannanase 322:364 the Neurospora crassa DFG-5 α-1,6-mannanase 322:364 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 7 53 theme wall 977:980 arg1 glycoproteins 982:994 cell wall glycoproteins 972:994 cell wall glycoproteins 972:994 Cell wall glycoproteins co-purify with DFG-5 demonstrating a specific association between DFG-5 and cell wall glycoproteins. 35306147 4 54 theme N-linked 607:614 arg1 galactomannan 616:628 the N-linked galactomannan 603:628 the N-linked galactomannan 603:628 We show that DFG-5 has an enzymatic activity and provide evidence that it processes the α-1,6-mannose backbone of the N-linked galactomannan. 35306147 5 55 theme complementation 661:675 arg1 experiments 677:687 complementation experiments 661:687 complementation experiments 661:687 Site-directed mutagenesis and complementation experiments show that D116 and D117 are located at the DFG-5 active site. 35306147 10 56 from galactomannans 1268:1281 arg1 proteins 1296:1303 cell wall proteins 1286:1303 cell wall proteins 1286:1303 By processing the galactomannans on cell wall proteins, DFG-5 targets them for cell wall incorporation by lichenin transferases. 35306147 0 57 theme wall 50:53 arg1 targeting 14:22 Extracellular targeting 0:22 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 0:90 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 35306147 6 58 theme opposite 802:809 arg1 side 811:814 the opposite side 798:814 the opposite side of the protein 798:829 D76 and E130, which are located in a groove on the opposite side of the protein, are also important for enzyme function. 35306147 1 59 theme cell 111:114 arg1 wall 116:119 a cell wall 109:119 a cell wall 109:119 The formation of a cell wall is vital for the survival and growth of a fungal cell. 35306147 9 60 theme final 1230:1234 arg1 destinations 1236:1247 their final destinations 1224:1247 their final destinations 1224:1247 DFG-5 plays a key role in targeting extracellular glycoproteins to their final destinations. 35306147 2 61 theme α-1,6-mannanases 220:235 arg1 family 210:215 the GH76 family 201:215 the GH76 family of α-1,6-mannanases 201:235 Fungi express members of the GH76 family of α-1,6-mannanases which play an important role in cell wall biogenesis. 35306147 7 62 theme cell 972:975 arg1 glycoproteins 982:994 cell wall glycoproteins 972:994 cell wall glycoproteins 972:994 Cell wall glycoproteins co-purify with DFG-5 demonstrating a specific association between DFG-5 and cell wall glycoproteins. 35306147 1 63 theme wall 116:119 arg1 formation 96:104 The formation 92:104 The formation of a cell wall 92:119 The formation of a cell wall is vital for the survival and growth of a fungal cell. 35306147 1 63 theme wall 116:119 arg1 vital 124:128 vital 124:128 vital 124:128 The formation of a cell wall is vital for the survival and growth of a fungal cell. 35306147 7 64 theme specific 933:940 arg1 association 942:952 a specific association 931:952 a specific association between DFG-5 and cell wall glycoproteins 931:994 Cell wall glycoproteins co-purify with DFG-5 demonstrating a specific association between DFG-5 and cell wall glycoproteins. 35306147 8 65 from present 1122:1128 arg1 glycoproteins 1142:1154 secreted glycoproteins 1133:1154 secreted glycoproteins 1133:1154 DFG-5 is able to discriminate between cell wall and secreted glycoproteins, and does not bind to the N-linked galactomannans present on secreted glycoproteins. 35306147 4 66 link N-linked 607:614 arg1 galactomannan 616:628 the N-linked galactomannan 603:628 the N-linked galactomannan 603:628 We show that DFG-5 has an enzymatic activity and provide evidence that it processes the α-1,6-mannose backbone of the N-linked galactomannan. 35306147 11 67 theme extracellular 1506:1518 arg1 medium 1520:1525 the extracellular medium 1502:1525 the extracellular medium 1502:1525 The N-linked galactomannans on secreted proteins are not processed by DFG-5, which targets these proteins for release into the extracellular medium. 35306147 3 68 theme galactomannan 441:453 arg1 backbone 417:424 the α-1,6-mannose backbone 399:424 the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins 399:486 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 0 69 theme glycoproteins 68:80 arg1 targeting 14:22 Extracellular targeting 0:22 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 0:90 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 35306147 5 70 from site 745:748 arg1 located 717:723 located 717:723 located 717:723 Site-directed mutagenesis and complementation experiments show that D116 and D117 are located at the DFG-5 active site. 35306147 2 71 theme family 210:215 arg1 members 190:196 members 190:196 members of the GH76 family of α-1,6-mannanases which play an important role in cell wall biogenesis 190:288 Fungi express members of the GH76 family of α-1,6-mannanases which play an important role in cell wall biogenesis. 35306147 5 72 located located 717:723 arg1 site 745:748 the DFG-5 active site 728:748 the DFG-5 active site 728:748 Site-directed mutagenesis and complementation experiments show that D116 and D117 are located at the DFG-5 active site. 35306147 5 72 located located 717:723 arg2 D117 708:711 D117 708:711 D117 708:711 Site-directed mutagenesis and complementation experiments show that D116 and D117 are located at the DFG-5 active site. 35306147 5 72 located located 717:723 arg2 D116 699:702 D116 699:702 D116 699:702 Site-directed mutagenesis and complementation experiments show that D116 and D117 are located at the DFG-5 active site. 35306147 11 73 link N-linked 1383:1390 arg1 galactomannans 1392:1405 The N-linked galactomannans 1379:1405 The N-linked galactomannans on secreted proteins 1379:1426 The N-linked galactomannans on secreted proteins are not processed by DFG-5, which targets these proteins for release into the extracellular medium. 35306147 0 74 theme secreted 59:66 arg1 glycoproteins 68:80 secreted glycoproteins 59:80 secreted glycoproteins 59:80 Extracellular targeting of Neurospora crassa cell wall and secreted glycoproteins by DFG-5. 35306147 2 75 theme GH76 205:208 arg1 family 210:215 the GH76 family 201:215 the GH76 family of α-1,6-mannanases 201:235 Fungi express members of the GH76 family of α-1,6-mannanases which play an important role in cell wall biogenesis. 35306147 3 76 located found 455:459 arg1 glycoproteins 474:486 cell wall glycoproteins 464:486 cell wall glycoproteins 464:486 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 3 76 located found 455:459 arg2 galactomannan 441:453 an N-linked galactomannan 429:453 an N-linked galactomannan found on cell wall glycoproteins 429:486 In this report we characterize the Neurospora crassa DFG-5 α-1,6-mannanase and demonstrate that it binds to the α-1,6-mannose backbone of an N-linked galactomannan found on cell wall glycoproteins. 35306147 8 77 theme secreted 1049:1056 arg1 glycoproteins 1058:1070 secreted glycoproteins 1049:1070 secreted glycoproteins 1049:1070 DFG-5 is able to discriminate between cell wall and secreted glycoproteins, and does not bind to the N-linked galactomannans present on secreted glycoproteins. 35306147 4 78 theme α-1,6-mannose 577:589 arg1 backbone 591:598 the α-1,6-mannose backbone 573:598 the α-1,6-mannose backbone of the N-linked galactomannan 573:628 We show that DFG-5 has an enzymatic activity and provide evidence that it processes the α-1,6-mannose backbone of the N-linked galactomannan. 36196760 5 0 theme important 746:754 arg1 role 756:759 an important role 743:759 an important role 743:759 Studies in mouse models indicate that NleA has an important role in bacterial virulence. 36196760 4 1 theme pathogen 664:671 arg1 rodentium 685:693 the related mouse pathogen Citrobacter rodentium 646:693 the related mouse pathogen Citrobacter rodentium 646:693 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 3 2 theme bacterial 426:434 arg1 proteins 436:443 Injected bacterial proteins 417:443 Injected bacterial proteins 417:443 Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. 36196760 4 3 theme rodentium 685:693 arg1 A 590:590 Non-LEE-encoded effector A 565:590 Non-LEE-encoded effector A (NleA) 565:597 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 4 3 theme rodentium 685:693 arg1 effector 618:625 a T3SS-injected effector 602:625 a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium 602:693 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 10 4 link O-linked 1451:1458 arg1 glycosylation 1460:1472 host-mediated O-linked glycosylation 1437:1472 host-mediated O-linked glycosylation 1437:1472 This is the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation. 36196760 9 5 theme non-modifiable 1149:1162 arg1 variant 1164:1170 a non-modifiable variant 1147:1170 a non-modifiable variant of NleA 1147:1178 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 9 5 theme non-modifiable 1149:1162 arg1 indistinguishable 1184:1200 indistinguishable 1184:1200 indistinguishable 1184:1200 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 10 6 theme host-mediated 1437:1449 arg1 glycosylation 1460:1472 host-mediated O-linked glycosylation 1437:1472 host-mediated O-linked glycosylation 1437:1472 This is the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation. 36196760 10 7 theme first 1375:1379 arg1 example 1387:1393 the first known example 1371:1393 the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation 1371:1472 This is the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation. 36196760 10 7 theme first 1375:1379 arg1 This 1363:1366 This 1363:1366 This 1363:1366 This is the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation. 36196760 1 8 theme responsible 188:198 arg1 coli 136:139 Escherichia coli 124:139 Escherichia coli 124:139 Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. 36196760 1 8 theme responsible 188:198 arg1 pathogens 178:186 gastrointestinal pathogens 161:186 gastrointestinal pathogens responsible for severe diarrheal illness 161:227 Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. 36196760 1 8 theme responsible 188:198 arg1 enteropathogenic 107:122 enteropathogenic 107:122 enteropathogenic 107:122 Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. 36196760 8 9 from isolates 1105:1112 arg1 present 1072:1078 present 1072:1078 present 1072:1078 Surprisingly, this region was not present in several clinical EHEC isolates. 36196760 5 10 contain has 739:741 arg2 role 756:759 an important role 743:759 an important role 743:759 Studies in mouse models indicate that NleA has an important role in bacterial virulence. 36196760 5 10 contain has 739:741 arg1 NleA 734:737 NleA 734:737 NleA 734:737 Studies in mouse models indicate that NleA has an important role in bacterial virulence. 36196760 10 11 theme effector 1410:1417 arg1 example 1387:1393 the first known example 1371:1393 the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation 1371:1472 This is the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation. 36196760 10 11 theme effector 1410:1417 arg1 This 1363:1366 This 1363:1366 This 1363:1366 This is the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation. 36196760 7 12 theme threonine-rich 944:957 arg1 cells 924:928 host cells 919:928 host cells 919:928 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 7 12 theme threonine-rich 944:957 arg1 region 959:964 a serine and threonine-rich region 931:964 region 959:964 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 0 13 gly glycosylation 69:81 arg1 NleA 31:34 The bacterial virulence factor NleA 0:34 The bacterial virulence factor NleA 0:34 The bacterial virulence factor NleA undergoes host-mediated O-linked glycosylation. 36196760 8 14 attach present 1072:1078 arg2 region 1057:1062 this region 1052:1062 this region 1052:1062 Surprisingly, this region was not present in several clinical EHEC isolates. 36196760 8 14 attach present 1072:1078 arg1 isolates 1105:1112 several clinical EHEC isolates 1083:1112 several clinical EHEC isolates 1083:1112 Surprisingly, this region was not present in several clinical EHEC isolates. 36196760 9 15 theme mixed 1328:1332 arg1 infections 1334:1343 mixed infections 1328:1343 mixed infections in C57BL/6J mice 1328:1360 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 7 16 link O-linked 1014:1021 arg1 glycosylation 1023:1035 host-mediated mucin-type O-linked glycosylation 989:1035 host-mediated mucin-type O-linked glycosylation 989:1035 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 9 17 theme C57BL/6J 1348:1355 arg1 mice 1357:1360 C57BL/6J mice 1348:1360 C57BL/6J mice 1348:1360 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 5 18 from Studies 696:702 arg1 models 713:718 mouse models 707:718 mouse models 707:718 Studies in mouse models indicate that NleA has an important role in bacterial virulence. 36196760 2 19 theme intestinal 358:367 arg1 cells 369:373 host intestinal cells 353:373 host intestinal cells 353:373 EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). 36196760 7 20 theme serine 933:938 arg1 cells 924:928 host cells 919:928 host cells 919:928 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 7 20 theme serine 933:938 arg1 region 959:964 a serine and threonine-rich region 931:964 region 959:964 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 1 21 theme diarrheal 211:219 arg1 illness 221:227 severe diarrheal illness 204:227 severe diarrheal illness 204:227 Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. 36196760 5 22 theme bacterial 764:772 arg1 virulence 774:782 bacterial virulence 764:782 bacterial virulence 764:782 Studies in mouse models indicate that NleA has an important role in bacterial virulence. 36196760 9 23 from increase 1272:1279 arg1 persistence 1284:1294 persistence 1284:1294 persistence 1284:1294 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 9 24 theme NleA 1175:1178 arg1 variant 1164:1170 a non-modifiable variant 1147:1170 a non-modifiable variant of NleA 1147:1178 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 9 24 theme NleA 1175:1178 arg1 indistinguishable 1184:1200 indistinguishable 1184:1200 indistinguishable 1184:1200 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 9 25 from infections 1334:1343 arg1 mice 1357:1360 C57BL/6J mice 1348:1360 C57BL/6J mice 1348:1360 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 9 25 from infections 1334:1343 arg1 course 1305:1310 the course 1301:1310 the course of infection in mixed infections in C57BL/6J mice 1301:1360 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 0 26 link O-linked 60:67 arg1 glycosylation 69:81 host-mediated O-linked glycosylation 46:81 host-mediated O-linked glycosylation 46:81 The bacterial virulence factor NleA undergoes host-mediated O-linked glycosylation. 36196760 1 27 theme severe 204:209 arg1 illness 221:227 severe diarrheal illness 204:227 severe diarrheal illness 204:227 Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. 36196760 0 28 theme bacterial 4:12 arg1 NleA 31:34 The bacterial virulence factor NleA 0:34 The bacterial virulence factor NleA 0:34 The bacterial virulence factor NleA undergoes host-mediated O-linked glycosylation. 36196760 4 29 theme Non-LEE-encoded 565:579 arg1 NleA 593:596 NleA 593:596 NleA 593:596 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 4 29 theme Non-LEE-encoded 565:579 arg1 A 590:590 Non-LEE-encoded effector A 565:590 Non-LEE-encoded effector A (NleA) 565:597 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 4 29 theme Non-LEE-encoded 565:579 arg1 effector 618:625 a T3SS-injected effector 602:625 a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium 602:693 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 9 30 from infection 1315:1323 arg1 infections 1334:1343 mixed infections 1328:1343 mixed infections in C57BL/6J mice 1328:1360 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 7 31 mod modified 977:984 arg3 glycosylation 1023:1035 host-mediated mucin-type O-linked glycosylation 989:1035 host-mediated mucin-type O-linked glycosylation 989:1035 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 7 31 mod modified 977:984 arg1 translocation 900:912 the following translocation 886:912 the following translocation into host cells, a serine and threonine-rich region of NleA 886:972 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 2 32 theme secretion 392:400 arg1 system 402:407 the type III secretion system 379:407 the type III secretion system (T3SS) 379:414 EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). 36196760 2 32 theme secretion 392:400 arg1 T3SS 410:413 T3SS 410:413 T3SS 410:413 EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). 36196760 9 33 theme infection 1315:1323 arg1 course 1305:1310 the course 1301:1310 the course of infection in mixed infections in C57BL/6J mice 1301:1360 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 9 34 from course 1305:1310 arg1 infections 1334:1343 mixed infections 1328:1343 mixed infections in C57BL/6J mice 1328:1360 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 9 35 theme wildtype 1207:1214 arg1 NleA 1216:1219 wildtype NleA 1207:1219 wildtype NleA in an acute mortality model 1207:1247 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 10 36 theme bacterial 1400:1408 arg1 effector 1410:1417 a bacterial effector 1398:1417 a bacterial effector being modified by host-mediated O-linked glycosylation 1398:1472 This is the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation. 36196760 0 37 theme factor 24:29 arg1 NleA 31:34 The bacterial virulence factor NleA 0:34 The bacterial virulence factor NleA 0:34 The bacterial virulence factor NleA undergoes host-mediated O-linked glycosylation. 36196760 7 38 theme host 919:922 arg1 cells 924:928 host cells 919:928 host cells 919:928 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 7 38 theme host 919:922 arg1 region 959:964 a serine and threonine-rich region 931:964 region 959:964 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 3 39 theme pathogen 555:562 arg1 survival 520:527 survival 520:527 survival 520:527 Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. 36196760 11 40 dep in 1580:1581 arg1 vivo 1583:1586 vivo 1583:1586 vivo 1583:1586 Our data also suggests that this modification may confer a selective disadvantage to the bacteria during in vivo infection. 36196760 3 41 theme functions 463:471 arg1 functions 463:471 functions 463:471 functions 463:471 Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. 36196760 3 41 theme functions 463:471 arg1 variety 452:458 a variety 450:458 a variety of functions 450:471 Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. 36196760 0 42 theme virulence 14:22 arg1 NleA 31:34 The bacterial virulence factor NleA 0:34 The bacterial virulence factor NleA 0:34 The bacterial virulence factor NleA undergoes host-mediated O-linked glycosylation. 36196760 4 43 theme effector 581:588 arg1 NleA 593:596 NleA 593:596 NleA 593:596 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 4 43 theme effector 581:588 arg1 A 590:590 Non-LEE-encoded effector A 565:590 Non-LEE-encoded effector A (NleA) 565:597 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 4 43 theme effector 581:588 arg1 effector 618:625 a T3SS-injected effector 602:625 a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium 602:693 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 4 44 theme Citrobacter 673:683 arg1 rodentium 685:693 the related mouse pathogen Citrobacter rodentium 646:693 the related mouse pathogen Citrobacter rodentium 646:693 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 2 45 dep form 244:247 arg1 inject 323:328 inject 323:328 inject proteins directly into host intestinal cells via the type III secretion system (T3SS) 323:414 EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). 36196760 3 46 theme cell 498:501 arg1 biology 503:509 host cell biology 493:509 host cell biology 493:509 Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. 36196760 8 47 theme several 1083:1089 arg1 isolates 1105:1112 several clinical EHEC isolates 1083:1112 several clinical EHEC isolates 1083:1112 Surprisingly, this region was not present in several clinical EHEC isolates. 36196760 4 48 theme EPEC 636:639 arg1 A 590:590 Non-LEE-encoded effector A 565:590 Non-LEE-encoded effector A (NleA) 565:597 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 4 48 theme EPEC 636:639 arg1 effector 618:625 a T3SS-injected effector 602:625 a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium 602:693 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 3 49 theme Injected 417:424 arg1 proteins 436:443 Injected bacterial proteins 417:443 Injected bacterial proteins 417:443 Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. 36196760 5 50 theme mouse 707:711 arg1 models 713:718 mouse models 707:718 mouse models 707:718 Studies in mouse models indicate that NleA has an important role in bacterial virulence. 36196760 9 51 theme acute 1227:1231 arg1 model 1243:1247 an acute mortality model 1224:1247 an acute mortality model 1224:1247 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 2 52 theme attaching 250:258 arg1 lesions 274:280 "attaching and effacing" lesions 249:280 "attaching and effacing" lesions 249:280 EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). 36196760 7 53 theme host-mediated 989:1001 arg1 glycosylation 1023:1035 host-mediated mucin-type O-linked glycosylation 989:1035 host-mediated mucin-type O-linked glycosylation 989:1035 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 0 54 theme O-linked 60:67 arg1 glycosylation 69:81 host-mediated O-linked glycosylation 46:81 host-mediated O-linked glycosylation 46:81 The bacterial virulence factor NleA undergoes host-mediated O-linked glycosylation. 36196760 4 55 theme related 650:656 arg1 rodentium 685:693 the related mouse pathogen Citrobacter rodentium 646:693 the related mouse pathogen Citrobacter rodentium 646:693 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 8 56 theme EHEC 1100:1103 arg1 isolates 1105:1112 several clinical EHEC isolates 1083:1112 several clinical EHEC isolates 1083:1112 Surprisingly, this region was not present in several clinical EHEC isolates. 36196760 9 57 theme mortality 1233:1241 arg1 model 1243:1247 an acute mortality model 1224:1247 an acute mortality model 1224:1247 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 7 58 theme mucin-type 1003:1012 arg1 glycosylation 1023:1035 host-mediated mucin-type O-linked glycosylation 989:1035 host-mediated mucin-type O-linked glycosylation 989:1035 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 3 59 theme host 493:496 arg1 biology 503:509 host cell biology 493:509 host cell biology 493:509 Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. 36196760 0 60 theme host-mediated 46:58 arg1 glycosylation 69:81 host-mediated O-linked glycosylation 46:81 host-mediated O-linked glycosylation 46:81 The bacterial virulence factor NleA undergoes host-mediated O-linked glycosylation. 36196760 8 61 theme clinical 1091:1098 arg1 isolates 1105:1112 several clinical EHEC isolates 1083:1112 several clinical EHEC isolates 1083:1112 Surprisingly, this region was not present in several clinical EHEC isolates. 36196760 10 62 theme O-linked 1451:1458 arg1 glycosylation 1460:1472 host-mediated O-linked glycosylation 1437:1472 host-mediated O-linked glycosylation 1437:1472 This is the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation. 36196760 2 63 theme host 353:356 arg1 cells 369:373 host intestinal cells 353:373 host intestinal cells 353:373 EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). 36196760 7 64 theme following 890:898 arg1 translocation 900:912 the following translocation 886:912 the following translocation into host cells, a serine and threonine-rich region of NleA 886:972 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 10 65 theme known 1381:1385 arg1 example 1387:1393 the first known example 1371:1393 the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation 1371:1472 This is the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation. 36196760 10 65 theme known 1381:1385 arg1 This 1363:1366 This 1363:1366 This 1363:1366 This is the first known example of a bacterial effector being modified by host-mediated O-linked glycosylation. 36196760 7 66 theme O-linked 1014:1021 arg1 glycosylation 1023:1035 host-mediated mucin-type O-linked glycosylation 989:1035 host-mediated mucin-type O-linked glycosylation 989:1035 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 9 67 theme C. 1133:1134 arg1 rodentium 1136:1144 C. rodentium 1133:1144 C. rodentium 1133:1144 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 11 68 theme in 1580:1581 arg1 infection 1588:1596 in vivo infection 1580:1596 in vivo infection 1580:1596 Our data also suggests that this modification may confer a selective disadvantage to the bacteria during in vivo infection. 36196760 7 69 theme NleA 969:972 arg1 cells 924:928 host cells 919:928 host cells 919:928 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 7 69 theme NleA 969:972 arg1 region 959:964 a serine and threonine-rich region 931:964 region 959:964 We have determined that the following translocation into host cells, a serine and threonine-rich region of NleA is modified by host-mediated mucin-type O-linked glycosylation. 36196760 4 70 theme mouse 658:662 arg1 rodentium 685:693 the related mouse pathogen Citrobacter rodentium 646:693 the related mouse pathogen Citrobacter rodentium 646:693 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 3 71 contain have 445:448 arg2 functions 463:471 functions 463:471 functions 463:471 Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. 36196760 3 71 contain have 445:448 arg1 proteins 436:443 Injected bacterial proteins 417:443 Injected bacterial proteins 417:443 Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. 36196760 3 71 contain have 445:448 arg2 variety 452:458 a variety 450:458 a variety of functions 450:471 Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. 36196760 2 72 theme " 272:272 arg1 lesions 274:280 "attaching and effacing" lesions 249:280 "attaching and effacing" lesions 249:280 EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). 36196760 4 73 theme EHEC 630:633 arg1 A 590:590 Non-LEE-encoded effector A 565:590 Non-LEE-encoded effector A (NleA) 565:597 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 4 73 theme EHEC 630:633 arg1 effector 618:625 a T3SS-injected effector 602:625 a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium 602:693 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 2 74 theme type 383:386 arg1 system 402:407 the type III secretion system 379:407 the type III secretion system (T3SS) 379:414 EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). 36196760 2 74 theme type 383:386 arg1 T3SS 410:413 T3SS 410:413 T3SS 410:413 EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). 36196760 11 75 theme selective 1534:1542 arg1 disadvantage 1544:1555 a selective disadvantage 1532:1555 a selective disadvantage 1532:1555 Our data also suggests that this modification may confer a selective disadvantage to the bacteria during in vivo infection. 36196760 8 76 from present 1072:1078 arg1 isolates 1105:1112 several clinical EHEC isolates 1083:1112 several clinical EHEC isolates 1083:1112 Surprisingly, this region was not present in several clinical EHEC isolates. 36196760 8 77 located present 1072:1078 arg2 region 1057:1062 this region 1052:1062 this region 1052:1062 Surprisingly, this region was not present in several clinical EHEC isolates. 36196760 8 77 located present 1072:1078 arg1 isolates 1105:1112 several clinical EHEC isolates 1083:1112 several clinical EHEC isolates 1083:1112 Surprisingly, this region was not present in several clinical EHEC isolates. 36196760 9 78 theme modest 1265:1270 arg1 increase 1272:1279 a modest increase 1263:1279 a modest increase in persistence 1263:1294 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 2 79 theme effacing 264:271 arg1 lesions 274:280 "attaching and effacing" lesions 249:280 "attaching and effacing" lesions 249:280 EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). 36196760 9 80 from NleA 1216:1219 arg1 variant 1164:1170 a non-modifiable variant 1147:1170 a non-modifiable variant of NleA 1147:1178 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 9 80 from NleA 1216:1219 arg1 indistinguishable 1184:1200 indistinguishable 1184:1200 indistinguishable 1184:1200 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 9 80 from NleA 1216:1219 arg1 model 1243:1247 an acute mortality model 1224:1247 an acute mortality model 1224:1247 When expressed in C. rodentium, a non-modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. 36196760 1 81 theme gastrointestinal 161:176 arg1 coli 136:139 Escherichia coli 124:139 Escherichia coli 124:139 Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. 36196760 1 81 theme gastrointestinal 161:176 arg1 pathogens 178:186 gastrointestinal pathogens 161:186 gastrointestinal pathogens responsible for severe diarrheal illness 161:227 Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. 36196760 1 81 theme gastrointestinal 161:176 arg1 enteropathogenic 107:122 enteropathogenic 107:122 enteropathogenic 107:122 Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. 36196760 4 82 theme T3SS-injected 604:616 arg1 A 590:590 Non-LEE-encoded effector A 565:590 Non-LEE-encoded effector A (NleA) 565:597 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 36196760 4 82 theme T3SS-injected 604:616 arg1 effector 618:625 a T3SS-injected effector 602:625 a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium 602:693 Non-LEE-encoded effector A (NleA) is a T3SS-injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. 34995107 5 0 theme X 689:689 arg1 production 698:707 sialyl Lewis X (sLeX) production 676:707 sialyl Lewis X (sLeX) production 676:707 In contrast, FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non-CSC population, and it antagonizes CSC function. 34995107 4 1 theme CSC 620:622 arg1 properties 624:633 CSC properties 620:633 CSC properties 620:633 This O-glycan is expressed on CD44 and promotes its interaction with hyaluronic acid, facilitating CD44 signaling and CSC properties. 34995107 7 2 theme differential 1000:1011 arg1 glycosylation 1013:1025 differential glycosylation 1000:1025 differential glycosylation 1000:1025 These data also reveal how differential glycosylation influences CSC fate. 34995107 2 3 theme α2,3 332:335 arg1 glycans 363:369 α2,3 sialylated core2 O-linked glycans 332:369 α2,3 sialylated core2 O-linked glycans 332:369 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 2 4 from models 271:276 arg1 Comparison 211:220 Comparison 211:220 Comparison of CSCs and non-CSCs from multiple breast cancer models 211:276 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 3 5 link O-linked 419:426 arg1 acids 440:444 O-linked α2,3 sialic acids 419:444 O-linked α2,3 sialic acids 419:444 We identified a lectin, SLBR-N, which binds to O-linked α2,3 sialic acids, that was able to enrich for CSCs in vitro and in vivo. 34995107 1 6 theme breast 149:154 arg1 cells 168:172 breast cancer stem cells 149:172 breast cancer stem cells (CSCs) 149:179 We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. 34995107 1 6 theme breast 149:154 arg1 CSCs 175:178 CSCs 175:178 CSCs 175:178 We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. 34995107 2 7 theme cancer 264:269 arg1 models 271:276 multiple breast cancer models 248:276 multiple breast cancer models 248:276 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 2 8 theme breast 257:262 arg1 models 271:276 multiple breast cancer models 248:276 multiple breast cancer models 248:276 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 0 9 from populations 44:54 arg1 cancer 66:71 breast cancer 59:71 breast cancer 59:71 O-linked α2,3 sialylation defines stem cell populations in breast cancer. 34995107 5 10 theme non-CSC 745:751 arg1 population 753:762 the non-CSC population 741:762 the non-CSC population 741:762 In contrast, FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non-CSC population, and it antagonizes CSC function. 34995107 0 11 link O-linked 0:7 arg1 sialylation 14:24 O-linked α2,3 sialylation 0:24 O-linked α2,3 sialylation 0:24 O-linked α2,3 sialylation defines stem cell populations in breast cancer. 34995107 2 12 theme multiple 248:255 arg1 models 271:276 multiple breast cancer models 248:276 multiple breast cancer models 248:276 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 1 13 theme cancer 156:161 arg1 cells 168:172 breast cancer stem cells 149:172 breast cancer stem cells (CSCs) 149:179 We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. 34995107 1 13 theme cancer 156:161 arg1 CSCs 175:178 CSCs 175:178 CSCs 175:178 We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. 34995107 1 14 used used 129:132 arg2 glycans 114:120 specific glycans 105:120 specific glycans 105:120 We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. 34995107 1 15 theme stem 163:166 arg1 cells 168:172 breast cancer stem cells 149:172 breast cancer stem cells (CSCs) 149:179 We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. 34995107 1 15 theme stem 163:166 arg1 CSCs 175:178 CSCs 175:178 CSCs 175:178 We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. 34995107 0 16 theme α2,3 9:12 arg1 sialylation 14:24 O-linked α2,3 sialylation 0:24 O-linked α2,3 sialylation 0:24 O-linked α2,3 sialylation defines stem cell populations in breast cancer. 34995107 6 17 theme status 965:970 arg1 issues 930:935 the issues 926:935 the issues of CD44 splicing and glycan status 926:970 Collectively, our data indicate that SLBR-N can be more efficient at enriching for CSCs than CD44 itself because its use avoids the issues of CD44 splicing and glycan status. 34995107 2 18 theme glycans 363:369 arg1 expression 318:327 expression 318:327 expression of α2,3 sialylated core2 O-linked glycans 318:369 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 0 19 theme O-linked 0:7 arg1 sialylation 14:24 O-linked α2,3 sialylation 0:24 O-linked α2,3 sialylation 0:24 O-linked α2,3 sialylation defines stem cell populations in breast cancer. 34995107 4 20 with interaction 554:564 arg1 acid 582:585 hyaluronic acid 571:585 hyaluronic acid 571:585 This O-glycan is expressed on CD44 and promotes its interaction with hyaluronic acid, facilitating CD44 signaling and CSC properties. 34995107 2 21 theme O-linked 354:361 arg1 glycans 363:369 α2,3 sialylated core2 O-linked glycans 332:369 α2,3 sialylated core2 O-linked glycans 332:369 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 2 22 gly sialylated 337:346 arg1 glycans 363:369 α2,3 sialylated core2 O-linked glycans 332:369 α2,3 sialylated core2 O-linked glycans 332:369 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 3 23 theme α2,3 428:431 arg1 acids 440:444 O-linked α2,3 sialic acids 419:444 O-linked α2,3 sialic acids 419:444 We identified a lectin, SLBR-N, which binds to O-linked α2,3 sialic acids, that was able to enrich for CSCs in vitro and in vivo. 34995107 3 24 theme sialic 433:438 arg1 acids 440:444 O-linked α2,3 sialic acids 419:444 O-linked α2,3 sialic acids 419:444 We identified a lectin, SLBR-N, which binds to O-linked α2,3 sialic acids, that was able to enrich for CSCs in vitro and in vivo. 34995107 0 25 theme cell 39:42 arg1 populations 44:54 stem cell populations 34:54 stem cell populations in breast cancer 34:71 O-linked α2,3 sialylation defines stem cell populations in breast cancer. 34995107 2 26 link O-linked 354:361 arg1 glycans 363:369 α2,3 sialylated core2 O-linked glycans 332:369 α2,3 sialylated core2 O-linked glycans 332:369 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 4 27 theme CD44 601:604 arg1 signaling 606:614 CD44 signaling 601:614 CD44 signaling 601:614 This O-glycan is expressed on CD44 and promotes its interaction with hyaluronic acid, facilitating CD44 signaling and CSC properties. 34995107 0 28 theme stem 34:37 arg1 populations 44:54 stem cell populations 34:54 stem cell populations in breast cancer 34:71 O-linked α2,3 sialylation defines stem cell populations in breast cancer. 34995107 3 29 theme O-linked 419:426 arg1 acids 440:444 O-linked α2,3 sialic acids 419:444 O-linked α2,3 sialic acids 419:444 We identified a lectin, SLBR-N, which binds to O-linked α2,3 sialic acids, that was able to enrich for CSCs in vitro and in vivo. 34995107 5 30 theme Lewis 683:687 arg1 sLeX 692:695 sLeX 692:695 sLeX 692:695 In contrast, FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non-CSC population, and it antagonizes CSC function. 34995107 5 30 theme Lewis 683:687 arg1 X 689:689 sialyl Lewis X 676:689 sialyl Lewis X (sLeX) production 676:707 In contrast, FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non-CSC population, and it antagonizes CSC function. 34995107 1 31 theme specific 105:112 arg1 glycans 114:120 specific glycans 105:120 specific glycans 105:120 We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. 34995107 7 32 theme CSC 1038:1040 arg1 fate 1042:1045 CSC fate 1038:1045 CSC fate 1038:1045 These data also reveal how differential glycosylation influences CSC fate. 34995107 2 33 theme non-CSCs 234:241 arg1 Comparison 211:220 Comparison 211:220 Comparison of CSCs and non-CSCs from multiple breast cancer models 211:276 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 5 34 theme CSC 784:786 arg1 function 788:795 CSC function 784:795 CSC function 784:795 In contrast, FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non-CSC population, and it antagonizes CSC function. 34995107 6 35 theme splicing 945:952 arg1 issues 930:935 the issues 926:935 the issues of CD44 splicing and glycan status 926:970 Collectively, our data indicate that SLBR-N can be more efficient at enriching for CSCs than CD44 itself because its use avoids the issues of CD44 splicing and glycan status. 34995107 5 36 theme sialyl 676:681 arg1 sLeX 692:695 sLeX 692:695 sLeX 692:695 In contrast, FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non-CSC population, and it antagonizes CSC function. 34995107 5 36 theme sialyl 676:681 arg1 X 689:689 sialyl Lewis X 676:689 sialyl Lewis X (sLeX) production 676:707 In contrast, FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non-CSC population, and it antagonizes CSC function. 34995107 4 37 theme hyaluronic 571:580 arg1 acid 582:585 hyaluronic acid 571:585 hyaluronic acid 571:585 This O-glycan is expressed on CD44 and promotes its interaction with hyaluronic acid, facilitating CD44 signaling and CSC properties. 34995107 2 38 theme CSCs 225:228 arg1 Comparison 211:220 Comparison 211:220 Comparison of CSCs and non-CSCs from multiple breast cancer models 211:276 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 6 39 theme CD44 940:943 arg1 splicing 945:952 CD44 splicing 940:952 CD44 splicing 940:952 Collectively, our data indicate that SLBR-N can be more efficient at enriching for CSCs than CD44 itself because its use avoids the issues of CD44 splicing and glycan status. 34995107 2 40 theme core2 348:352 arg1 glycans 363:369 α2,3 sialylated core2 O-linked glycans 332:369 α2,3 sialylated core2 O-linked glycans 332:369 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 34995107 6 41 theme glycan 958:963 arg1 status 965:970 glycan status 958:970 glycan status 958:970 Collectively, our data indicate that SLBR-N can be more efficient at enriching for CSCs than CD44 itself because its use avoids the issues of CD44 splicing and glycan status. 34995107 0 42 theme breast 59:64 arg1 cancer 66:71 breast cancer 59:71 breast cancer 59:71 O-linked α2,3 sialylation defines stem cell populations in breast cancer. 34995107 2 43 theme sialylated 337:346 arg1 glycans 363:369 α2,3 sialylated core2 O-linked glycans 332:369 α2,3 sialylated core2 O-linked glycans 332:369 Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. 35327245 7 0 theme inhibition 1142:1151 arg1 effects 1153:1159 inhibition effects 1142:1159 inhibition effects 1142:1159 All samples exerted inhibition effects on the intrinsic pathway FXII in a dose-dependent manner. 35327245 1 1 theme sulfate 183:189 arg1 groups 191:196 sulfate groups 183:196 sulfate groups 183:196 It is a challenge to degrade sulfated polysaccharides without stripping sulfate groups. 35327245 2 2 from algae 315:319 arg1 fucoidan 268:275 fucoidan 268:275 fucoidan 268:275 In the present study, a photocatalytic method was applied to degrade fucoidan, a sulfated polysaccharide from brown algae. 35327245 2 2 from algae 315:319 arg1 polysaccharide 289:302 a sulfated polysaccharide 278:302 a sulfated polysaccharide from brown algae 278:319 In the present study, a photocatalytic method was applied to degrade fucoidan, a sulfated polysaccharide from brown algae. 35327245 3 3 theme varying 343:349 arg1 H2O2 371:374 H2O2 371:374 H2O2 371:374 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 3 theme varying 343:349 arg1 amounts 360:366 varying addition amounts 343:366 varying addition amounts of H2O2 and TiO2 343:383 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 3 theme varying 343:349 arg1 TiO2 380:383 TiO2 380:383 TiO2 380:383 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 6 4 theme anticoagulant 996:1008 arg1 activity 1010:1017 anticoagulant activity 996:1017 anticoagulant activity as strong as fucoidan 996:1039 In addition, DF-0.5 showed anticoagulant activity as strong as fucoidan while DF-3 could specifically prolong the activated partial thromboplastin time. 35327245 4 5 with comparison 564:573 arg1 those 736:740 those 736:740 those 736:740 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 8 6 theme sulfated 1290:1297 arg1 fucoidan 1320:1327 sulfated low-molecular-weight fucoidan 1290:1327 sulfated low-molecular-weight fucoidan 1290:1327 Thus, photocatalytic degradation demonstrated the potential to prepare sulfated low-molecular-weight fucoidan with anticoagulant activity. 35327245 6 7 theme activated 1083:1091 arg1 time 1116:1119 the activated partial thromboplastin time 1079:1119 the activated partial thromboplastin time 1079:1119 In addition, DF-0.5 showed anticoagulant activity as strong as fucoidan while DF-3 could specifically prolong the activated partial thromboplastin time. 35327245 2 8 theme brown 309:313 arg1 algae 315:319 brown algae 309:319 brown algae 309:319 In the present study, a photocatalytic method was applied to degrade fucoidan, a sulfated polysaccharide from brown algae. 35327245 5 9 from oligosaccharides 882:897 arg1 DF-3 902:905 DF-3 902:905 DF-3 902:905 Moreover, 12 oligosaccharides in DF-3 were identified by HPLC-ESI-MSn and 10 of them were sulfated. 35327245 3 10 theme TiO2 380:383 arg1 H2O2 371:374 H2O2 371:374 H2O2 371:374 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 10 theme TiO2 380:383 arg1 amounts 360:366 varying addition amounts 343:366 varying addition amounts of H2O2 and TiO2 343:383 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 10 theme TiO2 380:383 arg1 TiO2 380:383 TiO2 380:383 TiO2 380:383 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 4 11 dep degradation 783:793 arg1 reduced 833:839 reduced 833:839 reduced the galactose/fucose ratio 833:866 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 4 11 dep degradation 783:793 arg1 strip 803:807 strip 803:807 strip 803:807 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 8 12 theme low-molecular-weight 1299:1318 arg1 fucoidan 1320:1327 sulfated low-molecular-weight fucoidan 1290:1327 sulfated low-molecular-weight fucoidan 1290:1327 Thus, photocatalytic degradation demonstrated the potential to prepare sulfated low-molecular-weight fucoidan with anticoagulant activity. 35327245 7 13 theme pathway 1178:1184 arg1 FXII 1186:1189 the intrinsic pathway FXII 1164:1189 the intrinsic pathway FXII in a dose-dependent manner 1164:1216 All samples exerted inhibition effects on the intrinsic pathway FXII in a dose-dependent manner. 35327245 6 14 theme thromboplastin 1101:1114 arg1 time 1116:1119 the activated partial thromboplastin time 1079:1119 the activated partial thromboplastin time 1079:1119 In addition, DF-0.5 showed anticoagulant activity as strong as fucoidan while DF-3 could specifically prolong the activated partial thromboplastin time. 35327245 8 15 theme photocatalytic 1225:1238 arg1 degradation 1240:1250 photocatalytic degradation 1225:1250 photocatalytic degradation 1225:1250 Thus, photocatalytic degradation demonstrated the potential to prepare sulfated low-molecular-weight fucoidan with anticoagulant activity. 35327245 6 16 theme partial 1093:1099 arg1 time 1116:1119 the activated partial thromboplastin time 1079:1119 the activated partial thromboplastin time 1079:1119 In addition, DF-0.5 showed anticoagulant activity as strong as fucoidan while DF-3 could specifically prolong the activated partial thromboplastin time. 35327245 3 17 theme H2O2 371:374 arg1 H2O2 371:374 H2O2 371:374 H2O2 371:374 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 17 theme H2O2 371:374 arg1 amounts 360:366 varying addition amounts 343:366 varying addition amounts of H2O2 and TiO2 343:383 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 17 theme H2O2 371:374 arg1 TiO2 380:383 TiO2 380:383 TiO2 380:383 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 0 18 theme Anticoagulant 50:62 arg1 Activity 64:71 Anticoagulant Activity 50:71 Anticoagulant Activity 50:71 Preparation of Low-Molecular-Weight Fucoidan with Anticoagulant Activity by Photocatalytic Degradation Method. 35327245 2 19 theme sulfated 280:287 arg1 fucoidan 268:275 fucoidan 268:275 fucoidan 268:275 In the present study, a photocatalytic method was applied to degrade fucoidan, a sulfated polysaccharide from brown algae. 35327245 2 19 theme sulfated 280:287 arg1 polysaccharide 289:302 a sulfated polysaccharide 278:302 a sulfated polysaccharide from brown algae 278:319 In the present study, a photocatalytic method was applied to degrade fucoidan, a sulfated polysaccharide from brown algae. 35327245 4 20 theme photocatalytic 768:781 arg1 degradation 783:793 the photocatalytic degradation 764:793 the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio 764:866 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 3 21 theme addition 351:358 arg1 H2O2 371:374 H2O2 371:374 H2O2 371:374 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 21 theme addition 351:358 arg1 amounts 360:366 varying addition amounts 343:366 varying addition amounts of H2O2 and TiO2 343:383 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 21 theme addition 351:358 arg1 TiO2 380:383 TiO2 380:383 TiO2 380:383 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 22 theme % 554:554 arg1 H2O2 556:559 0.95% H2O2 550:559 0.95% H2O2 550:559 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 7 23 from FXII 1186:1189 arg1 manner 1211:1216 a dose-dependent manner 1194:1216 a dose-dependent manner 1194:1216 All samples exerted inhibition effects on the intrinsic pathway FXII in a dose-dependent manner. 35327245 3 24 theme high 403:406 arg1 HPGPC 451:455 HPGPC 451:455 HPGPC 451:455 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 24 theme high 403:406 arg1 chromatography 435:448 high performance gel permeation chromatography 403:448 high performance gel permeation chromatography (HPGPC) 403:456 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 7 25 theme intrinsic 1168:1176 arg1 FXII 1186:1189 the intrinsic pathway FXII 1164:1189 the intrinsic pathway FXII in a dose-dependent manner 1164:1216 All samples exerted inhibition effects on the intrinsic pathway FXII in a dose-dependent manner. 35327245 4 26 theme kDa 683:685 arg1 Mw 677:678 average Mw 669:678 average Mw 90 kDa 669:685 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 4 27 theme average 698:704 arg1 kDa 711:713 average Mw 3 kDa 698:713 average Mw 3 kDa 698:713 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 4 27 theme average 698:704 arg1 DF-3 692:695 DF-3 692:695 DF-3 692:695 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 3 28 with degradation 326:336 arg1 H2O2 371:374 H2O2 371:374 H2O2 371:374 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 28 with degradation 326:336 arg1 amounts 360:366 varying addition amounts 343:366 varying addition amounts of H2O2 and TiO2 343:383 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 28 with degradation 326:336 arg1 TiO2 380:383 TiO2 380:383 TiO2 380:383 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 0 29 theme Fucoidan 36:43 arg1 Preparation 0:10 Preparation 0:10 Preparation of Low-Molecular-Weight Fucoidan with Anticoagulant Activity by Photocatalytic Degradation Method. 0:109 Preparation of Low-Molecular-Weight Fucoidan with Anticoagulant Activity by Photocatalytic Degradation Method. 35327245 4 30 theme products 609:616 arg1 compositions 591:602 the chemical compositions 578:602 the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, 578:729 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 0 31 theme Low-Molecular-Weight 15:34 arg1 Fucoidan 36:43 Low-Molecular-Weight Fucoidan 15:43 Low-Molecular-Weight Fucoidan with Anticoagulant Activity 15:71 Preparation of Low-Molecular-Weight Fucoidan with Anticoagulant Activity by Photocatalytic Degradation Method. 35327245 2 32 theme present 206:212 arg1 study 214:218 the present study 202:218 the present study 202:218 In the present study, a photocatalytic method was applied to degrade fucoidan, a sulfated polysaccharide from brown algae. 35327245 3 33 theme 0.95 550:553 arg1 % 554:554 % 554:554 % 554:554 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 8 34 theme anticoagulant 1334:1346 arg1 activity 1348:1355 anticoagulant activity 1334:1355 anticoagulant activity 1334:1355 Thus, photocatalytic degradation demonstrated the potential to prepare sulfated low-molecular-weight fucoidan with anticoagulant activity. 35327245 3 35 theme permeation 424:433 arg1 HPGPC 451:455 HPGPC 451:455 HPGPC 451:455 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 35 theme permeation 424:433 arg1 chromatography 435:448 high performance gel permeation chromatography 403:448 high performance gel permeation chromatography (HPGPC) 403:456 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 4 36 theme galactose/fucose 845:860 arg1 ratio 862:866 the galactose/fucose ratio 841:866 the galactose/fucose ratio 841:866 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 3 37 theme thin 462:465 arg1 TLC 489:491 TLC 489:491 TLC 489:491 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 37 theme thin 462:465 arg1 chromatography 473:486 thin layer chromatography 462:486 thin layer chromatography (TLC) 462:492 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 0 38 with Fucoidan 36:43 arg1 Activity 64:71 Anticoagulant Activity 50:71 Anticoagulant Activity 50:71 Preparation of Low-Molecular-Weight Fucoidan with Anticoagulant Activity by Photocatalytic Degradation Method. 35327245 3 39 theme layer 467:471 arg1 TLC 489:491 TLC 489:491 TLC 489:491 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 39 theme layer 467:471 arg1 chromatography 473:486 thin layer chromatography 462:486 thin layer chromatography (TLC) 462:492 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 40 theme performance 408:418 arg1 HPGPC 451:455 HPGPC 451:455 HPGPC 451:455 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 40 theme performance 408:418 arg1 chromatography 435:448 high performance gel permeation chromatography 403:448 high performance gel permeation chromatography (HPGPC) 403:456 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 4 41 theme sulfate 813:819 arg1 groups 821:826 the sulfate groups 809:826 the sulfate groups 809:826 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 4 42 theme average 669:675 arg1 Mw 677:678 average Mw 669:678 average Mw 90 kDa 669:685 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 3 43 theme gel 420:422 arg1 HPGPC 451:455 HPGPC 451:455 HPGPC 451:455 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 43 theme gel 420:422 arg1 chromatography 435:448 high performance gel permeation chromatography 403:448 high performance gel permeation chromatography (HPGPC) 403:456 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 2 44 theme photocatalytic 223:236 arg1 method 238:243 a photocatalytic method 221:243 a photocatalytic method 221:243 In the present study, a photocatalytic method was applied to degrade fucoidan, a sulfated polysaccharide from brown algae. 35327245 5 45 theme them 949:952 arg1 10 943:944 10 943:944 10 943:944 Moreover, 12 oligosaccharides in DF-3 were identified by HPLC-ESI-MSn and 10 of them were sulfated. 35327245 5 45 theme them 949:952 arg1 them 949:952 them 949:952 them 949:952 Moreover, 12 oligosaccharides in DF-3 were identified by HPLC-ESI-MSn and 10 of them were sulfated. 35327245 1 46 theme sulfated 140:147 arg1 polysaccharides 149:163 sulfated polysaccharides 140:163 sulfated polysaccharides 140:163 It is a challenge to degrade sulfated polysaccharides without stripping sulfate groups. 35327245 4 47 theme chemical 582:589 arg1 compositions 591:602 the chemical compositions 578:602 the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, 578:729 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 3 48 theme 5 538:538 arg1 % 539:539 % 539:539 % 539:539 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 3 49 theme % 539:539 arg1 TiO2 541:544 5% TiO2 538:544 5% TiO2 538:544 The degradation with varying addition amounts of H2O2 and TiO2 were monitored by high performance gel permeation chromatography (HPGPC) and thin layer chromatography (TLC), and fucoidan was efficiently degraded with 5% TiO2 and 0.95% H2O2. 35327245 7 50 theme dose-dependent 1196:1209 arg1 manner 1211:1216 a dose-dependent manner 1194:1216 a dose-dependent manner 1194:1216 All samples exerted inhibition effects on the intrinsic pathway FXII in a dose-dependent manner. 35327245 4 51 theme 90 680:681 arg1 kDa 683:685 kDa 683:685 kDa 683:685 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 0 52 theme Degradation 91:101 arg1 Method 103:108 Photocatalytic Degradation Method 76:108 Photocatalytic Degradation Method 76:108 Preparation of Low-Molecular-Weight Fucoidan with Anticoagulant Activity by Photocatalytic Degradation Method. 35327245 4 53 dep h 637:637 arg1 illumination 647:658 illumination 647:658 illumination 647:658 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 6 54 theme strong 1022:1027 arg1 activity 1010:1017 anticoagulant activity 996:1017 anticoagulant activity as strong as fucoidan 996:1039 In addition, DF-0.5 showed anticoagulant activity as strong as fucoidan while DF-3 could specifically prolong the activated partial thromboplastin time. 35327245 0 55 theme Photocatalytic 76:89 arg1 Method 103:108 Photocatalytic Degradation Method 76:108 Photocatalytic Degradation Method 76:108 Preparation of Low-Molecular-Weight Fucoidan with Anticoagulant Activity by Photocatalytic Degradation Method. 35327245 4 56 theme Mw 706:707 arg1 kDa 711:713 average Mw 3 kDa 698:713 average Mw 3 kDa 698:713 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 4 56 theme Mw 706:707 arg1 DF-3 692:695 DF-3 692:695 DF-3 692:695 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 4 57 dep DF-0.5 661:666 arg1 Mw 677:678 average Mw 669:678 average Mw 90 kDa 669:685 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35327245 4 58 theme compositions 591:602 arg1 comparison 564:573 A comparison 562:573 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan 562:752 A comparison of the chemical compositions of 2 products obtained after 0.5 h and 3 h illumination, DF-0.5 (average Mw 90 kDa) and DF-3 (average Mw 3 kDa), respectively, with those of fucoidan indicates the photocatalytic degradation did not strip the sulfate groups, but reduced the galactose/fucose ratio. 35999637 4 0 theme surface 929:935 arg1 expression 937:946 reduced cell surface expression 916:946 reduced cell surface expression 916:946 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 1 theme proteolytic 1242:1252 arg1 cleavage 1254:1261 proteolytic cleavage 1242:1261 proteolytic cleavage 1242:1261 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 1 2 gly glycoproteins 160:172 arg1 glycoproteins 160:172 viral glycoproteins 154:172 viral glycoproteins 154:172 BACKGROUND N-linked glycans on viral glycoproteins have been shown to be important for protein expression, processing and intracellular transport. 35999637 5 3 theme N-linked 1338:1345 arg1 modifications 1347:1359 the individual N-linked modifications 1323:1359 the individual N-linked modifications 1323:1359 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 5 3 theme N-linked 1338:1345 arg1 dispensable 1399:1409 dispensable 1399:1409 dispensable 1399:1409 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 2 4 theme potential 331:339 arg1 sites 357:361 six potential N-glycosylation sites 327:361 six potential N-glycosylation sites 327:361 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 1 5 theme intracellular 245:257 arg1 transport 259:267 intracellular transport 245:267 intracellular transport 245:267 BACKGROUND N-linked glycans on viral glycoproteins have been shown to be important for protein expression, processing and intracellular transport. 35999637 5 6 link N-linked 1338:1345 arg1 modifications 1347:1359 the individual N-linked modifications 1323:1359 the individual N-linked modifications 1323:1359 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 5 6 link N-linked 1338:1345 arg1 dispensable 1399:1409 dispensable 1399:1409 dispensable 1399:1409 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 4 7 theme cell 1205:1208 arg1 surface 1210:1216 the cell surface 1201:1216 the cell surface 1201:1216 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 2 8 theme glycoprotein 281:292 arg1 F 294:294 The fusion glycoprotein F 270:294 The fusion glycoprotein F of Cedar virus (CedV) 270:316 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 4 9 from removal 849:855 arg1 subunit 896:902 the F1 subunit 889:902 the F1 subunit 889:902 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 10 from removal 651:657 arg1 subunit 718:724 the CedV F2 subunit 706:724 the CedV F2 subunit 706:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 11 theme surface 763:769 arg1 transport 771:779 cell surface transport 758:779 cell surface transport 758:779 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 12 theme Most 1045:1048 arg1 effects 1060:1066 Most prominent effects 1045:1066 Most prominent effects 1045:1066 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 13 theme N-glycan 662:669 arg1 N66 675:677 N66 675:677 N66 675:677 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 13 theme N-glycan 662:669 arg1 g1 671:672 N-glycan g1 662:672 N-glycan g1 (N66) 662:678 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 13 theme N-glycan 662:669 arg1 N98 698:700 N98 698:700 N98 698:700 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 5 14 theme glycan 1384:1389 arg1 g4 1391:1392 glycan g4 1384:1392 glycan g4 1384:1392 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 2 15 theme virus 305:309 arg1 F 294:294 The fusion glycoprotein F 270:294 The fusion glycoprotein F of Cedar virus (CedV) 270:316 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 4 16 theme F. 831:832 arg1 activity 814:821 fusion activity 807:821 fusion activity 807:821 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 16 theme F. 831:832 arg1 cleavage 794:801 proteolytic cleavage 782:801 proteolytic cleavage 782:801 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 0 17 theme fusion 107:112 arg1 protein 114:120 the Cedar virus fusion protein 91:120 the Cedar virus fusion protein 91:120 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 4 18 theme CedV 1012:1015 arg1 protein 1034:1040 the CedV receptor-binding protein 1008:1040 the CedV receptor-binding protein 1008:1040 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 19 dep no 730:731 arg1 G. 1042:1043 G. 1042:1043 G. 1042:1043 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 20 theme fusion 807:812 arg1 activity 814:821 fusion activity 807:821 fusion activity 807:821 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 6 21 theme proteolytic 1581:1591 arg1 activation 1593:1602 proteolytic activation 1581:1602 proteolytic activation 1581:1602 However, removal of g4 led to a phenotype that was strongly impaired concerning cell surface expression and proteolytic activation. 35999637 4 22 theme g2 681:682 arg1 removal 651:657 The individual removal 636:657 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit 636:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 3 23 dep Asn 538:540 arg1 to 542:543 to 542:543 to 542:543 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 3 23 dep Asn 538:540 arg1 Gln 545:547 Gln 545:547 Asn to Gln 538:547 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 5 24 theme transfection 1447:1458 arg1 experiments 1460:1470 transfection experiments 1447:1470 transfection experiments 1447:1470 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 1 25 theme BACKGROUND 123:132 arg1 glycans 143:149 BACKGROUND N-linked glycans 123:149 BACKGROUND N-linked glycans on viral glycoproteins 123:172 BACKGROUND N-linked glycans on viral glycoproteins have been shown to be important for protein expression, processing and intracellular transport. 35999637 6 26 theme cell 1553:1556 arg1 expression 1566:1575 cell surface expression 1553:1575 cell surface expression 1553:1575 However, removal of g4 led to a phenotype that was strongly impaired concerning cell surface expression and proteolytic activation. 35999637 3 27 from impact 394:399 arg1 surface 409:415 cell surface transport, proteolytic cleavage and biological activity 404:471 cell surface transport, proteolytic cleavage and biological activity 404:471 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 3 28 theme N-glycosylation 591:605 arg1 sites 607:611 the six potential N-glycosylation sites 573:611 the six potential N-glycosylation sites 573:611 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 5 29 from processing 1415:1424 arg1 experiments 1460:1470 transfection experiments 1447:1470 transfection experiments 1447:1470 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 5 30 theme g4 1391:1392 arg1 exception 1371:1379 the exception 1367:1379 the exception of glycan g4 1367:1392 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 0 31 theme surface 70:76 arg1 transport 78:86 cell surface transport 65:86 cell surface transport 65:86 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 2 32 contain contains 318:325 arg1 F 294:294 The fusion glycoprotein F 270:294 The fusion glycoprotein F of Cedar virus (CedV) 270:316 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 2 32 contain contains 318:325 arg2 sites 357:361 six potential N-glycosylation sites 327:361 six potential N-glycosylation sites 327:361 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 1 33 theme viral 154:158 arg1 glycoproteins 160:172 viral glycoproteins 154:172 viral glycoproteins 154:172 BACKGROUND N-linked glycans on viral glycoproteins have been shown to be important for protein expression, processing and intracellular transport. 35999637 4 34 theme glycan 869:874 arg1 removal 849:855 removal 849:855 removal of N-linked glycan g6 (N463) in the F1 subunit 849:902 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 3 35 theme proteolytic 428:438 arg1 cleavage 440:447 proteolytic cleavage 428:447 proteolytic cleavage 428:447 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 0 36 theme Cedar 95:99 arg1 protein 114:120 the Cedar virus fusion protein 91:120 the Cedar virus fusion protein 91:120 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 4 37 theme N-glycosylation 1112:1126 arg1 g4 1134:1135 N-glycosylation motif g4 1112:1135 N-glycosylation motif g4 (N413) 1112:1142 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 37 theme N-glycosylation 1112:1126 arg1 N413 1138:1141 N413 1138:1141 N413 1138:1141 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 38 theme cell 924:927 arg1 expression 937:946 reduced cell surface expression 916:946 reduced cell surface expression 916:946 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 5 39 theme F 1434:1434 arg1 protein 1436:1442 CedV F protein 1429:1442 CedV F protein 1429:1442 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 4 40 theme g4 1134:1135 arg1 disruption 1098:1107 the disruption 1094:1107 the disruption 1094:1107 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 3 41 dep mutations 527:535 arg1 Asn 538:540 Asn 538:540 Asn to Gln 538:547 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 3 42 theme cell 404:407 arg1 surface 409:415 cell surface transport, proteolytic cleavage and biological activity 404:471 cell surface transport, proteolytic cleavage and biological activity 404:471 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 1 43 link N-linked 134:141 arg1 glycans 143:149 BACKGROUND N-linked glycans 123:149 BACKGROUND N-linked glycans on viral glycoproteins 123:172 BACKGROUND N-linked glycans on viral glycoproteins have been shown to be important for protein expression, processing and intracellular transport. 35999637 0 44 theme glycosylation 21:33 arg1 role 4:7 The role 0:7 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 0:121 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 4 45 theme F 1196:1196 arg1 transport 1178:1186 the transport 1174:1186 the transport of CedV F to the cell surface 1174:1216 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 46 theme little 741:746 arg1 effect 748:753 only little effect 736:753 only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein 736:1040 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 0 47 theme proteolytic 38:48 arg1 processing 50:59 proteolytic processing 38:59 proteolytic processing 38:59 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 4 48 theme F2 715:716 arg1 subunit 718:724 the CedV F2 subunit 706:724 the CedV F2 subunit 706:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 1 49 theme protein 210:216 arg1 expression 218:227 protein expression 210:227 protein expression 210:227 BACKGROUND N-linked glycans on viral glycoproteins have been shown to be important for protein expression, processing and intracellular transport. 35999637 4 50 attach removal 849:855 arg2 glycan 869:874 N-linked glycan g6 (N463) 860:884 N-linked glycan g6 (N463) 860:884 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 50 attach removal 849:855 arg3 subunit 896:902 the F1 subunit 889:902 the F1 subunit 889:902 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 3 51 theme conservative 514:525 arg1 mutations 527:535 conservative mutations 514:535 conservative mutations (Asn to Gln) 514:548 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 2 52 theme N-glycosylation 341:355 arg1 sites 357:361 six potential N-glycosylation sites 327:361 six potential N-glycosylation sites 327:361 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 0 53 link N-linked 12:19 arg1 glycosylation 21:33 N-linked glycosylation 12:33 N-linked glycosylation 12:33 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 2 54 gly glycoprotein 281:292 arg1 glycoprotein 281:292 The fusion glycoprotein F 270:294 The fusion glycoprotein F of Cedar virus (CedV) 270:316 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 4 55 from g1 671:672 arg1 subunit 718:724 the CedV F2 subunit 706:724 the CedV F2 subunit 706:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 56 theme proteolytic 782:792 arg1 cleavage 794:801 proteolytic cleavage 782:801 proteolytic cleavage 782:801 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 2 57 theme fusion 274:279 arg1 F 294:294 The fusion glycoprotein F 270:294 The fusion glycoprotein F of Cedar virus (CedV) 270:316 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 3 58 gly N-glycosylation 591:605 arg2 sites 607:611 the six potential N-glycosylation sites 573:611 the six potential N-glycosylation sites 573:611 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 3 58 gly N-glycosylation 591:605 arg2 six 577:579 six 577:579 six 577:579 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 4 59 theme prominent 1050:1058 arg1 effects 1060:1066 Most prominent effects 1045:1066 Most prominent effects 1045:1066 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 60 theme individual 640:649 arg1 removal 651:657 The individual removal 636:657 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit 636:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 61 theme cell 758:761 arg1 transport 771:779 cell surface transport 758:779 cell surface transport 758:779 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 0 62 theme protein 114:120 arg1 transport 78:86 cell surface transport 65:86 cell surface transport 65:86 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 0 62 theme protein 114:120 arg1 processing 50:59 proteolytic processing 38:59 proteolytic processing 38:59 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 5 63 theme individual 1327:1336 arg1 modifications 1347:1359 the individual N-linked modifications 1323:1359 the individual N-linked modifications 1323:1359 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 5 63 theme individual 1327:1336 arg1 dispensable 1399:1409 dispensable 1399:1409 dispensable 1399:1409 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 2 64 theme Cedar 299:303 arg1 CedV 312:315 CedV 312:315 CedV 312:315 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 2 64 theme Cedar 299:303 arg1 virus 305:309 Cedar virus 299:309 Cedar virus (CedV) 299:316 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 4 65 theme receptor-binding 1017:1032 arg1 protein 1034:1040 the CedV receptor-binding protein 1008:1040 the CedV receptor-binding protein 1008:1040 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 6 66 theme g4 1493:1494 arg1 removal 1482:1488 removal 1482:1488 removal of g4 1482:1494 However, removal of g4 led to a phenotype that was strongly impaired concerning cell surface expression and proteolytic activation. 35999637 4 67 dep glycan 869:874 arg1 N463 880:883 N463 880:883 N463 880:883 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 68 theme fusion 1267:1272 arg1 activity 1274:1281 fusion activity 1267:1281 fusion activity 1267:1281 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 3 69 theme sites 607:611 arg1 five 565:568 five 565:568 five 565:568 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 3 69 theme sites 607:611 arg1 sites 607:611 the six potential N-glycosylation sites 573:611 the six potential N-glycosylation sites 573:611 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 6 70 theme surface 1558:1564 arg1 expression 1566:1575 cell surface expression 1553:1575 cell surface expression 1553:1575 However, removal of g4 led to a phenotype that was strongly impaired concerning cell surface expression and proteolytic activation. 35999637 4 71 contain had 726:728 arg1 removal 651:657 The individual removal 636:657 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit 636:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 71 contain had 726:728 arg2 no 730:731 no 730:731 no 730:731 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 71 contain had 726:728 arg2 effect 748:753 only little effect 736:753 only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein 736:1040 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 0 72 theme cell 65:68 arg1 transport 78:86 cell surface transport 65:86 cell surface transport 65:86 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 3 73 theme potential 581:589 arg1 sites 607:611 the six potential N-glycosylation sites 573:611 the six potential N-glycosylation sites 573:611 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 4 74 from subunit 718:724 arg1 removal 651:657 The individual removal 636:657 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit 636:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 1 75 theme N-linked 134:141 arg1 glycans 143:149 BACKGROUND N-linked glycans 123:149 BACKGROUND N-linked glycans on viral glycoproteins 123:172 BACKGROUND N-linked glycans on viral glycoproteins have been shown to be important for protein expression, processing and intracellular transport. 35999637 4 76 theme g1 671:672 arg1 removal 651:657 The individual removal 636:657 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit 636:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 77 with co-expression 989:1001 arg1 protein 1034:1040 the CedV receptor-binding protein 1008:1040 the CedV receptor-binding protein 1008:1040 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 0 78 from role 4:7 arg1 transport 78:86 cell surface transport 65:86 cell surface transport 65:86 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 0 78 from role 4:7 arg1 processing 50:59 proteolytic processing 38:59 proteolytic processing 38:59 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 0 79 theme virus 101:105 arg1 protein 114:120 the Cedar virus fusion protein 91:120 the Cedar virus fusion protein 91:120 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 1 80 from glycans 143:149 arg1 glycoproteins 160:172 viral glycoproteins 154:172 viral glycoproteins 154:172 BACKGROUND N-linked glycans on viral glycoproteins have been shown to be important for protein expression, processing and intracellular transport. 35999637 4 81 theme N-linked 860:867 arg1 glycan 869:874 N-linked glycan g6 (N463) 860:884 N-linked glycan g6 (N463) 860:884 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 82 theme motif 1128:1132 arg1 g4 1134:1135 N-glycosylation motif g4 1112:1135 N-glycosylation motif g4 (N413) 1112:1142 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 82 theme motif 1128:1132 arg1 N413 1138:1141 N413 1138:1141 N413 1138:1141 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 83 dep F. 831:832 arg1 resulted 904:911 resulted 904:911 resulted in reduced cell surface expression 904:946 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 84 from effect 748:753 arg1 fusogenicity 971:982 slightly increased fusogenicity 952:982 slightly increased fusogenicity 952:982 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 84 from effect 748:753 arg1 transport 771:779 cell surface transport 758:779 cell surface transport 758:779 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 84 from effect 748:753 arg1 cleavage 794:801 proteolytic cleavage 782:801 proteolytic cleavage 782:801 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 85 from g3 694:695 arg1 subunit 718:724 the CedV F2 subunit 706:724 the CedV F2 subunit 706:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 5 86 dep CONCLUSIONS 1284:1294 arg1 indicate 1309:1316 indicate 1309:1316 indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments 1309:1470 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 3 87 used utilized 626:633 arg2 five 565:568 five 565:568 five 565:568 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 3 87 used utilized 626:633 arg2 sites 607:611 the six potential N-glycosylation sites 573:611 the six potential N-glycosylation sites 573:611 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 3 88 dep surface 409:415 arg1 transport 417:425 transport 417:425 transport 417:425 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 3 88 dep surface 409:415 arg1 cleavage 440:447 proteolytic cleavage 428:447 proteolytic cleavage 428:447 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 3 88 dep surface 409:415 arg1 activity 464:471 biological activity 453:471 biological activity 453:471 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 0 89 theme N-linked 12:19 arg1 glycosylation 21:33 N-linked glycosylation 12:33 N-linked glycosylation 12:33 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 4 90 theme reduced 916:922 arg1 expression 937:946 reduced cell surface expression 916:946 reduced cell surface expression 916:946 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 5 91 theme protein 1436:1442 arg1 processing 1415:1424 processing 1415:1424 processing of CedV F protein in transfection experiments 1415:1470 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 4 92 theme CedV 1191:1194 arg1 F 1196:1196 CedV F 1191:1196 CedV F 1191:1196 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 93 theme g3 694:695 arg1 removal 651:657 The individual removal 636:657 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit 636:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 2 94 gly N-glycosylation 341:355 arg2 sites 357:361 six potential N-glycosylation sites 327:361 six potential N-glycosylation sites 327:361 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 2 94 gly N-glycosylation 341:355 arg2 six 327:329 six 327:329 six 327:329 The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. 35999637 3 95 theme biological 453:462 arg1 activity 464:471 biological activity 453:471 biological activity 453:471 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 4 96 theme F1 893:894 arg1 subunit 896:902 the F1 subunit 889:902 the F1 subunit 889:902 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 97 link N-linked 860:867 arg1 glycan 869:874 N-linked glycan g6 (N463) 860:884 N-linked glycan g6 (N463) 860:884 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 3 98 theme consensus 491:499 arg1 sequences 501:509 the consensus sequences 487:509 the consensus sequences 487:509 FINDINGS To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. 35999637 5 99 with modifications 1347:1359 arg1 exception 1371:1379 the exception 1367:1379 the exception of glycan g4 1367:1392 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 0 100 gly glycosylation 21:33 arg1 surface 70:76 cell surface transport 65:86 cell surface transport 65:86 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 0 100 gly glycosylation 21:33 arg1 protein 114:120 the Cedar virus fusion protein 91:120 the Cedar virus fusion protein 91:120 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 0 100 gly glycosylation 21:33 arg1 cell 65:68 cell surface transport 65:86 cell surface transport 65:86 The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein. 35999637 4 101 theme increased 961:969 arg1 fusogenicity 971:982 slightly increased fusogenicity 952:982 slightly increased fusogenicity 952:982 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 5 102 theme CedV 1429:1432 arg1 protein 1436:1442 CedV F protein 1429:1442 CedV F protein 1429:1442 CONCLUSIONS Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. 35999637 4 103 theme CedV 710:713 arg1 subunit 718:724 the CedV F2 subunit 706:724 the CedV F2 subunit 706:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 35999637 4 104 from g2 681:682 arg1 subunit 718:724 the CedV F2 subunit 706:724 the CedV F2 subunit 706:724 The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. 36533382 10 0 theme CD62P 1347:1351 arg1 higher 1392:1397 higher 1392:1397 higher 1392:1397 The expression of CD62P in platelets in patients with IgAN was higher than those of healthy controls. 36533382 10 0 theme CD62P 1347:1351 arg1 expression 1333:1342 The expression 1329:1342 The expression of CD62P in platelets in patients with IgAN 1329:1386 The expression of CD62P in platelets in patients with IgAN was higher than those of healthy controls. 36533382 7 1 with patients 1079:1086 arg1 counts 1108:1113 lower platelet counts 1093:1113 lower platelet counts 1093:1113 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 5 2 theme platelet 665:672 arg1 counts 674:679 lower platelet counts 659:679 the lower platelet counts group 655:685 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 9 3 with patients 1309:1316 arg1 IgAN 1323:1326 IgAN 1323:1326 IgAN 1323:1326 Furthermore, we investigated whether platelets were activated and released ST6Gal-1 in patients with IgAN. 36533382 10 4 with patients 1369:1376 arg1 IgAN 1383:1386 IgAN 1383:1386 IgAN 1383:1386 The expression of CD62P in platelets in patients with IgAN was higher than those of healthy controls. 36533382 8 5 theme composite 1175:1183 arg1 endpoints 1192:1200 composite kidney endpoints 1175:1200 composite kidney endpoints 1175:1200 No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. 36533382 7 6 theme cell 1048:1051 arg1 ratio 1053:1057 platelet large cell ratio 1033:1057 platelet large cell ratio 1033:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 7 theme serum 839:843 arg1 C3 845:846 serum C3 839:846 serum C3 839:846 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 8 8 theme endpoints 1192:1200 arg1 terms 1145:1149 terms 1145:1149 terms of the eGFR decline and composite kidney endpoints between two groups 1145:1219 No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. 36533382 7 9 theme platelet 1033:1040 arg1 ratio 1053:1057 platelet large cell ratio 1033:1057 platelet large cell ratio 1033:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 12 10 dep CONCLUSIONS 1639:1649 arg1 contain 1694:1700 contain 1694:1700 contain ST6Gal-1, which may be released by the activation of platelets in IgAN 1694:1771 CONCLUSIONS In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN. 36533382 2 11 theme glycosylation 301:313 arg1 events 315:320 cell surface glycosylation events 288:320 cell surface glycosylation events in circulation 288:335 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 7 12 theme IgA 834:836 arg1 levels 824:829 higher levels 817:829 higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2 817:923 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 12 theme IgA 834:836 arg1 levels 932:937 lower levels 926:937 lower levels of platelet distribution width 926:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 12 theme IgA 834:836 arg1 volume 992:997 the mean platelet volume 974:997 the mean platelet volume 974:997 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 12 theme IgA 834:836 arg1 percentage 1019:1028 a lower percentage 1011:1028 a lower percentage of platelet large cell ratio 1011:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 13 theme crits 906:910 arg1 percentages 882:892 higher percentages 875:892 higher percentages of platelet crits 875:910 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 13 theme crits 906:910 arg1 T1/2 920:923 T1/2 920:923 T1/2 920:923 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 13 theme crits 906:910 arg1 IgA 834:836 IgA 834:836 IgA 834:836 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 13 theme crits 906:910 arg1 C4 855:856 serum C4 849:856 serum C4 849:856 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 13 theme crits 906:910 arg1 proteinuria 862:872 proteinuria 862:872 proteinuria 862:872 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 13 theme crits 906:910 arg1 S1 913:914 S1 913:914 S1 913:914 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 13 theme crits 906:910 arg1 C3 845:846 serum C3 839:846 serum C3 839:846 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 12 14 theme circulating 1672:1682 arg1 platelets 1684:1692 human circulating platelets 1666:1692 human circulating platelets 1666:1692 CONCLUSIONS In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN. 36533382 2 15 theme cell 288:291 arg1 events 315:320 cell surface glycosylation events 288:320 cell surface glycosylation events in circulation 288:335 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 5 16 from patients 560:567 arg1 group 599:603 the higher platelet counts group 572:603 the higher platelet counts group 572:603 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 4 17 theme ST6Gal-1 443:450 arg1 levels 452:457 ST6Gal-1 levels 443:457 ST6Gal-1 levels 443:457 ST6Gal-1 levels were analyzed before and after activation of platelets by flow cytometry. 36533382 7 18 theme mean 978:981 arg1 volume 992:997 the mean platelet volume 974:997 the mean platelet volume 974:997 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 8 19 theme decline 1163:1169 arg1 terms 1145:1149 terms 1145:1149 terms of the eGFR decline and composite kidney endpoints between two groups 1145:1219 No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. 36533382 1 20 dep BACKGROUND 72:81 arg1 showed 102:107 showed 102:107 showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN) 102:246 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 5 21 theme IgAN 555:558 arg1 patients 560:567 IgAN patients 555:567 IgAN patients in the higher platelet counts group 555:603 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 1 22 theme α2,6-sialyltransferase 127:148 arg1 levels 163:168 ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels 109:168 ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma 109:178 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 5 23 theme counts 592:597 arg1 group 599:603 the higher platelet counts group 572:603 the higher platelet counts group 572:603 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 7 24 theme distribution 951:962 arg1 width 964:968 platelet distribution width 942:968 platelet distribution width 942:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 1 25 dep showed 102:107 arg1 associated 185:194 associated 185:194 showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN) 102:246 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 0 26 from supply 22:27 arg1 patients 41:48 patients 41:48 patients with IgA Nephropathy 41:69 Circulating platelets supply ST6Gal-1 in patients with IgA Nephropathy. 36533382 7 27 theme lower 926:930 arg1 levels 932:937 lower levels 926:937 lower levels of platelet distribution width 926:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 2 28 from events 315:320 arg1 circulation 325:335 circulation 325:335 circulation 325:335 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 11 29 theme ST6Gal-1 1464:1471 arg1 levels 1473:1478 ST6Gal-1 levels 1464:1478 ST6Gal-1 levels 1464:1478 There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. 36533382 11 30 theme obvious 1445:1451 arg1 changes 1453:1459 no obvious changes 1442:1459 no obvious changes in ST6Gal-1 levels between the rest 1442:1495 There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. 36533382 12 31 contain contain 1694:1700 arg2 ST6Gal-1 1702:1709 ST6Gal-1 1702:1709 ST6Gal-1 1702:1709 CONCLUSIONS In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN. 36533382 12 31 contain contain 1694:1700 arg1 platelets 1684:1692 human circulating platelets 1666:1692 human circulating platelets 1666:1692 CONCLUSIONS In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN. 36533382 12 31 contain contain 1694:1700 arg2 platelets 1684:1692 human circulating platelets 1666:1692 human circulating platelets 1666:1692 CONCLUSIONS In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN. 36533382 12 31 contain contain 1694:1700 arg1 conclusion 1654:1663 conclusion 1654:1663 conclusion 1654:1663 CONCLUSIONS In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN. 36533382 7 32 theme T1/2 920:923 arg1 levels 824:829 higher levels 817:829 higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2 817:923 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 32 theme T1/2 920:923 arg1 levels 932:937 lower levels 926:937 lower levels of platelet distribution width 926:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 32 theme T1/2 920:923 arg1 volume 992:997 the mean platelet volume 974:997 the mean platelet volume 974:997 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 32 theme T1/2 920:923 arg1 percentage 1019:1028 a lower percentage 1011:1028 a lower percentage of platelet large cell ratio 1011:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 10 33 theme healthy 1413:1419 arg1 controls 1421:1428 healthy controls 1413:1428 healthy controls 1413:1428 The expression of CD62P in platelets in patients with IgAN was higher than those of healthy controls. 36533382 6 34 theme positive 700:707 arg1 correlation 709:719 a positive correlation 698:719 a positive correlation between platelet counts and ST6Gal-1 levels in plasma 698:773 There was a positive correlation between platelet counts and ST6Gal-1 levels in plasma. 36533382 7 35 theme S1 913:914 arg1 levels 824:829 higher levels 817:829 higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2 817:923 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 35 theme S1 913:914 arg1 levels 932:937 lower levels 926:937 lower levels of platelet distribution width 926:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 35 theme S1 913:914 arg1 volume 992:997 the mean platelet volume 974:997 the mean platelet volume 974:997 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 35 theme S1 913:914 arg1 percentage 1019:1028 a lower percentage 1011:1028 a lower percentage of platelet large cell ratio 1011:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 0 36 theme Circulating 0:10 arg1 platelets 12:20 Circulating platelets 0:20 Circulating platelets 0:20 Circulating platelets supply ST6Gal-1 in patients with IgA Nephropathy. 36533382 5 37 theme higher 576:581 arg1 counts 592:597 higher platelet counts 576:597 the higher platelet counts group 572:603 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 8 38 dep decline 1163:1169 arg1 the 1154:1156 the 1154:1156 the 1154:1156 No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. 36533382 7 39 theme platelet 797:804 arg1 counts 806:811 higher platelet counts 790:811 higher platelet counts 790:811 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 1 40 theme ST6 109:111 arg1 α2,6-sialyltransferase 127:148 ST6 β-galactoside α2,6-sialyltransferase 1 109:150 ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma 109:178 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 1 40 theme ST6 109:111 arg1 ST6Gal-1 153:160 ST6Gal-1 153:160 ST6Gal-1 153:160 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 7 41 theme platelet 1099:1106 arg1 counts 1108:1113 lower platelet counts 1093:1113 lower platelet counts 1093:1113 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 11 42 theme 4-hour 1617:1622 arg1 incubation 1627:1636 4-hour of incubation 1617:1636 4-hour of incubation 1617:1636 There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. 36533382 12 43 theme platelets 1755:1763 arg1 activation 1741:1750 the activation 1737:1750 the activation of platelets in IgAN 1737:1771 CONCLUSIONS In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN. 36533382 3 44 dep METHODS 372:378 arg1 total 382:386 A total 380:386 METHODS A total of 180 patients with IgAN 372:412 METHODS A total of 180 patients with IgAN were included in this study. 36533382 6 45 theme ST6Gal-1 749:756 arg1 levels 758:763 ST6Gal-1 levels 749:763 ST6Gal-1 levels 749:763 There was a positive correlation between platelet counts and ST6Gal-1 levels in plasma. 36533382 7 46 theme platelet 897:904 arg1 crits 906:910 platelet crits 897:910 platelet crits 897:910 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 1 47 theme IgA 225:227 arg1 IgAN 242:245 IgAN 242:245 IgAN 242:245 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 1 47 theme IgA 225:227 arg1 nephropathy 229:239 IgA nephropathy 225:239 IgA nephropathy (IgAN) 225:246 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 7 48 theme ratio 1053:1057 arg1 levels 824:829 higher levels 817:829 higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2 817:923 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 48 theme ratio 1053:1057 arg1 levels 932:937 lower levels 926:937 lower levels of platelet distribution width 926:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 48 theme ratio 1053:1057 arg1 volume 992:997 the mean platelet volume 974:997 the mean platelet volume 974:997 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 48 theme ratio 1053:1057 arg1 percentage 1019:1028 a lower percentage 1011:1028 a lower percentage of platelet large cell ratio 1011:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 49 theme percentages 882:892 arg1 levels 824:829 higher levels 817:829 higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2 817:923 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 49 theme percentages 882:892 arg1 levels 932:937 lower levels 926:937 lower levels of platelet distribution width 926:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 49 theme percentages 882:892 arg1 volume 992:997 the mean platelet volume 974:997 the mean platelet volume 974:997 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 49 theme percentages 882:892 arg1 percentage 1019:1028 a lower percentage 1011:1028 a lower percentage of platelet large cell ratio 1011:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 11 50 theme ST6Gal-1 1572:1579 arg1 levels 1581:1586 ST6Gal-1 levels 1572:1586 ST6Gal-1 levels 1572:1586 There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. 36533382 2 51 from circulation 325:335 arg1 regulator 275:283 the crucial regulator 263:283 the crucial regulator of cell surface glycosylation events in circulation 263:335 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 2 51 from circulation 325:335 arg1 Platelets 249:257 Platelets 249:257 Platelets 249:257 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 6 52 from counts 738:743 arg1 plasma 768:773 plasma 768:773 plasma 768:773 There was a positive correlation between platelet counts and ST6Gal-1 levels in plasma. 36533382 1 53 theme slower 203:208 arg1 progression 210:220 a slower progression 201:220 a slower progression of IgA nephropathy (IgAN) 201:246 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 5 54 theme lower 659:663 arg1 counts 674:679 lower platelet counts 659:679 the lower platelet counts group 655:685 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 7 55 with Patients 776:783 arg1 counts 806:811 higher platelet counts 790:811 higher platelet counts 790:811 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 6 56 from levels 758:763 arg1 plasma 768:773 plasma 768:773 plasma 768:773 There was a positive correlation between platelet counts and ST6Gal-1 levels in plasma. 36533382 7 57 theme large 1042:1046 arg1 ratio 1053:1057 platelet large cell ratio 1033:1057 platelet large cell ratio 1033:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 2 58 theme crucial 267:273 arg1 regulator 275:283 the crucial regulator 263:283 the crucial regulator of cell surface glycosylation events in circulation 263:335 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 2 58 theme crucial 267:273 arg1 Platelets 249:257 Platelets 249:257 Platelets 249:257 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 7 59 theme serum 849:853 arg1 C4 855:856 serum C4 849:856 serum C4 849:856 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 12 60 theme human 1666:1670 arg1 platelets 1684:1692 human circulating platelets 1666:1692 human circulating platelets 1666:1692 CONCLUSIONS In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN. 36533382 5 61 theme ST6Gal-1 632:639 arg1 levels 622:627 higher levels 615:627 higher levels of ST6Gal-1 615:639 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 11 62 theme activated 1505:1513 arg1 platelets 1515:1523 the activated platelets 1501:1523 the activated platelets within 1 to 2-hour 1501:1542 There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. 36533382 2 63 theme events 315:320 arg1 regulator 275:283 the crucial regulator 263:283 the crucial regulator of cell surface glycosylation events in circulation 263:335 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 2 63 theme events 315:320 arg1 Platelets 249:257 Platelets 249:257 Platelets 249:257 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 7 64 theme C3 845:846 arg1 levels 824:829 higher levels 817:829 higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2 817:923 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 64 theme C3 845:846 arg1 levels 932:937 lower levels 926:937 lower levels of platelet distribution width 926:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 64 theme C3 845:846 arg1 volume 992:997 the mean platelet volume 974:997 the mean platelet volume 974:997 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 64 theme C3 845:846 arg1 percentage 1019:1028 a lower percentage 1011:1028 a lower percentage of platelet large cell ratio 1011:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 5 65 dep RESULTS 533:539 arg1 found 544:548 found 544:548 found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group 544:685 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 8 66 theme kidney 1185:1190 arg1 endpoints 1192:1200 composite kidney endpoints 1175:1200 composite kidney endpoints 1175:1200 No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. 36533382 7 67 theme lower 1013:1017 arg1 percentage 1019:1028 a lower percentage 1011:1028 a lower percentage of platelet large cell ratio 1011:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 2 68 theme surface 293:299 arg1 events 315:320 cell surface glycosylation events 288:320 cell surface glycosylation events in circulation 288:335 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 1 69 from levels 163:168 arg1 plasma 173:178 plasma 173:178 plasma 173:178 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 7 70 contain had 813:815 arg2 levels 932:937 lower levels 926:937 lower levels of platelet distribution width 926:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 70 contain had 813:815 arg2 levels 824:829 higher levels 817:829 higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2 817:923 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 70 contain had 813:815 arg2 percentage 1019:1028 a lower percentage 1011:1028 a lower percentage of platelet large cell ratio 1011:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 70 contain had 813:815 arg1 Patients 776:783 Patients 776:783 Patients with higher platelet counts 776:811 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 70 contain had 813:815 arg2 volume 992:997 the mean platelet volume 974:997 the mean platelet volume 974:997 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 11 71 dep 2-hour 1537:1542 arg1 to 1534:1535 to 1534:1535 to 1534:1535 There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. 36533382 5 72 theme counts 674:679 arg1 group 681:685 the lower platelet counts group 655:685 the lower platelet counts group 655:685 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 7 73 theme platelet 983:990 arg1 volume 992:997 the mean platelet volume 974:997 the mean platelet volume 974:997 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 1 74 theme β-galactoside 113:125 arg1 α2,6-sialyltransferase 127:148 ST6 β-galactoside α2,6-sialyltransferase 1 109:150 ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma 109:178 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 1 74 theme β-galactoside 113:125 arg1 ST6Gal-1 153:160 ST6Gal-1 153:160 ST6Gal-1 153:160 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 8 75 theme eGFR 1158:1161 arg1 decline 1163:1169 eGFR decline 1158:1169 eGFR decline 1158:1169 No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. 36533382 7 76 theme width 964:968 arg1 levels 824:829 higher levels 817:829 higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2 817:923 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 76 theme width 964:968 arg1 levels 932:937 lower levels 926:937 lower levels of platelet distribution width 926:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 76 theme width 964:968 arg1 volume 992:997 the mean platelet volume 974:997 the mean platelet volume 974:997 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 7 76 theme width 964:968 arg1 percentage 1019:1028 a lower percentage 1011:1028 a lower percentage of platelet large cell ratio 1011:1057 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 2 77 from regulator 275:283 arg1 circulation 325:335 circulation 325:335 circulation 325:335 Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. 36533382 4 78 theme platelets 504:512 arg1 activation 490:499 activation 490:499 activation of platelets by flow cytometry 490:530 ST6Gal-1 levels were analyzed before and after activation of platelets by flow cytometry. 36533382 7 79 theme platelet 942:949 arg1 width 964:968 platelet distribution width 942:968 platelet distribution width 942:968 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 4 80 theme flow 517:520 arg1 cytometry 522:530 flow cytometry 517:530 flow cytometry 517:530 ST6Gal-1 levels were analyzed before and after activation of platelets by flow cytometry. 36533382 3 81 with patients 395:402 arg1 IgAN 409:412 IgAN 409:412 IgAN 409:412 METHODS A total of 180 patients with IgAN were included in this study. 36533382 5 82 theme higher 615:620 arg1 levels 622:627 higher levels 615:627 higher levels of ST6Gal-1 615:639 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 11 83 from changes 1453:1459 arg1 levels 1473:1478 ST6Gal-1 levels 1464:1478 ST6Gal-1 levels 1464:1478 There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. 36533382 1 84 theme previous 87:94 arg1 study 96:100 Our previous study 83:100 Our previous study 83:100 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 3 85 theme patients 395:402 arg1 total 382:386 A total 380:386 METHODS A total of 180 patients with IgAN 372:412 METHODS A total of 180 patients with IgAN were included in this study. 36533382 7 86 theme higher 817:822 arg1 levels 824:829 higher levels 817:829 higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2 817:923 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 5 87 theme platelet 583:590 arg1 counts 592:597 higher platelet counts 576:597 the higher platelet counts group 572:603 RESULTS We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. 36533382 11 88 theme of 1624:1625 arg1 incubation 1627:1636 4-hour of incubation 1617:1636 4-hour of incubation 1617:1636 There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. 36533382 7 89 theme lower 1093:1097 arg1 counts 1108:1113 lower platelet counts 1093:1113 lower platelet counts 1093:1113 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 11 90 from difference 1558:1567 arg1 levels 1581:1586 ST6Gal-1 levels 1572:1586 ST6Gal-1 levels 1572:1586 There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. 36533382 8 91 located found 1136:1140 arg2 differences 1119:1129 No differences 1116:1129 No differences 1116:1129 No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. 36533382 8 91 located found 1136:1140 arg1 terms 1145:1149 terms 1145:1149 terms of the eGFR decline and composite kidney endpoints between two groups 1145:1219 No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. 36533382 0 92 theme IgA 55:57 arg1 Nephropathy 59:69 IgA Nephropathy 55:69 IgA Nephropathy 55:69 Circulating platelets supply ST6Gal-1 in patients with IgA Nephropathy. 36533382 7 93 theme higher 790:795 arg1 counts 806:811 higher platelet counts 790:811 higher platelet counts 790:811 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 10 94 from expression 1333:1342 arg1 platelets 1356:1364 platelets 1356:1364 platelets in patients with IgAN 1356:1386 The expression of CD62P in platelets in patients with IgAN was higher than those of healthy controls. 36533382 12 95 from activation 1741:1750 arg1 IgAN 1768:1771 IgAN 1768:1771 IgAN 1768:1771 CONCLUSIONS In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN. 36533382 0 96 with patients 41:48 arg1 Nephropathy 59:69 IgA Nephropathy 55:69 IgA Nephropathy 55:69 Circulating platelets supply ST6Gal-1 in patients with IgA Nephropathy. 36533382 7 97 theme higher 875:880 arg1 percentages 882:892 higher percentages 875:892 higher percentages of platelet crits 875:910 Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. 36533382 1 98 theme nephropathy 229:239 arg1 progression 210:220 a slower progression 201:220 a slower progression of IgA nephropathy (IgAN) 201:246 BACKGROUND Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). 36533382 10 99 from platelets 1356:1364 arg1 patients 1369:1376 patients 1369:1376 patients with IgAN 1369:1386 The expression of CD62P in platelets in patients with IgAN was higher than those of healthy controls. 36533382 6 100 theme platelet 729:736 arg1 counts 738:743 platelet counts 729:743 platelet counts 729:743 There was a positive correlation between platelet counts and ST6Gal-1 levels in plasma. 36891885 10 0 theme versatile 1581:1589 arg1 toolkit 1599:1605 a versatile genetic toolkit 1579:1605 a versatile genetic toolkit for AGP complexity in ferns 1579:1633 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 6 1 theme sugar 908:912 arg1 3-O-methylrhamnose 914:931 the unusual sugar 3-O-methylrhamnose 896:931 the unusual sugar 3-O-methylrhamnose 896:931 Yet, unlike AGPs of angiosperms, those of ferns contained the unusual sugar 3-O-methylrhamnose. 36891885 5 2 theme plant 679:683 arg1 AGPs 685:688 seed plant AGPs 674:688 seed plant AGPs 674:688 The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. 36891885 8 3 theme structural 1171:1180 arg1 differences 1182:1192 the structural differences 1167:1192 the structural differences between AGPs of ferns and seed plants 1167:1230 Antibodies directed against carbohydrate epitopes of AGPs supported the structural differences between AGPs of ferns and seed plants. 36891885 10 4 theme AGP 1611:1613 arg1 complexity 1615:1624 AGP complexity 1611:1624 AGP complexity 1611:1624 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 10 5 theme Phylogenetic 1444:1455 arg1 analyses 1457:1464 Phylogenetic analyses 1444:1464 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis 1444:1517 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 1 6 theme tracheophytes 185:197 arg1 evolution 152:160 evolution 152:160 evolution 152:160 Significant changes have occurred in plant cell wall composition during evolution and diversification of tracheophytes. 36891885 1 6 theme tracheophytes 185:197 arg1 diversification 166:180 diversification 166:180 diversification 166:180 Significant changes have occurred in plant cell wall composition during evolution and diversification of tracheophytes. 36891885 12 7 theme hallmark 1788:1795 arg1 feature 1797:1803 the hallmark feature 1784:1803 the hallmark feature of tracheophytes: their elaborate cell walls 1784:1848 This diversity sheds light on the evolution of the hallmark feature of tracheophytes: their elaborate cell walls. 36891885 7 8 from type 992:995 arg1 ferns 1012:1016 the ferns 1008:1016 the ferns 1008:1016 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 5 9 theme carbohydrate 651:662 arg1 moiety 664:669 The carbohydrate moiety 647:669 The carbohydrate moiety of seed plant AGPs 647:688 The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. 36891885 2 10 theme evolutionary 290:301 arg1 changes 303:309 evolutionary changes 290:309 evolutionary changes across tracheophytes 290:330 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 7 11 from Araf 1000:1003 arg1 ferns 1012:1016 the ferns 1008:1016 the ferns 1008:1016 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 8 12 theme plants 1225:1230 arg1 AGPs 1202:1205 AGPs 1202:1205 AGPs of ferns and seed plants 1202:1230 Antibodies directed against carbohydrate epitopes of AGPs supported the structural differences between AGPs of ferns and seed plants. 36891885 9 13 theme linkage 1251:1257 arg1 types 1259:1263 AGP linkage types 1247:1263 AGP linkage types across the streptophyte lineage 1247:1295 Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. 36891885 2 14 theme seed 225:228 arg1 plants 230:235 seed plants 225:235 seed plants 225:235 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 7 15 theme Araf 1000:1003 arg1 type 992:995 the main linkage type 975:995 the main linkage type of Araf in the ferns 975:1016 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 7 15 theme Araf 1000:1003 arg1 Araf 1033:1036 1,2-linked Araf 1022:1036 1,2-linked Araf 1022:1036 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 1 16 theme cell 123:126 arg1 composition 133:143 plant cell wall composition 117:143 plant cell wall composition 117:143 Significant changes have occurred in plant cell wall composition during evolution and diversification of tracheophytes. 36891885 7 17 theme 1,2-linked 1022:1031 arg1 Araf 1033:1036 1,2-linked Araf 1022:1036 1,2-linked Araf 1022:1036 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 7 17 theme 1,2-linked 1022:1031 arg1 type 992:995 the main linkage type 975:995 the main linkage type of Araf in the ferns 975:1016 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 2 18 theme cell 255:258 arg1 wall 260:263 the cell wall 251:263 the cell wall 251:263 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 4 19 from Salvinia 620:627 arg1 AGPs 569:572 the AGPs 565:572 the AGPs from the leptosporangiate fern genera Azolla, Salvinia and Ceratopteris 565:644 Here, we characterize the AGPs from the leptosporangiate fern genera Azolla, Salvinia and Ceratopteris. 36891885 9 20 theme streptophyte 1276:1287 arg1 lineage 1289:1295 the streptophyte lineage 1272:1295 the streptophyte lineage 1272:1295 Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. 36891885 7 21 theme main 979:982 arg1 type 992:995 the main linkage type 975:995 the main linkage type of Araf in the ferns 975:1016 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 7 21 theme main 979:982 arg1 Araf 1033:1036 1,2-linked Araf 1022:1036 1,2-linked Araf 1022:1036 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 0 22 from walls 10:14 arg1 streptophytes 65:77 streptophytes 65:77 streptophytes 65:77 Fern cell walls and the evolution of arabinogalactan-proteins in streptophytes. 36891885 2 23 dep key 277:279 arg1 track 284:288 track 284:288 to track evolutionary changes across tracheophytes 281:330 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 2 23 dep key 277:279 arg1 understand 339:348 understand 339:348 to understand seed plant-specific evolutionary innovations 336:393 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 4 24 from Azolla 612:617 arg1 AGPs 569:572 the AGPs 565:572 the AGPs from the leptosporangiate fern genera Azolla, Salvinia and Ceratopteris 565:644 Here, we characterize the AGPs from the leptosporangiate fern genera Azolla, Salvinia and Ceratopteris. 36891885 7 25 link 1,5-linked 1062:1071 arg1 Araf 1073:1076 1,5-linked Araf 1062:1076 1,5-linked Araf 1062:1076 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 5 26 theme pyranosidic 761:771 arg1 galactose 773:781 1,3,6-linked pyranosidic galactose 748:781 1,3,6-linked pyranosidic galactose 748:781 The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. 36891885 1 27 theme Significant 80:90 arg1 changes 92:98 Significant changes 80:98 Significant changes 80:98 Significant changes have occurred in plant cell wall composition during evolution and diversification of tracheophytes. 36891885 2 28 from knowledge 238:246 arg1 wall 260:263 the cell wall 251:263 the cell wall 251:263 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 3 29 theme Fern 396:399 arg1 composition 411:421 Fern cell wall composition 396:421 Fern cell wall composition 396:421 Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). 36891885 10 30 theme AGP 1502:1504 arg1 biosynthesis 1506:1517 AGP biosynthesis 1502:1517 AGP biosynthesis 1502:1517 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 12 31 dep walls 1844:1848 arg1 elaborate 1829:1837 elaborate 1829:1837 elaborate 1829:1837 This diversity sheds light on the evolution of the hallmark feature of tracheophytes: their elaborate cell walls. 36891885 0 32 theme Fern 0:3 arg1 walls 10:14 Fern cell walls 0:14 Fern cell walls 0:14 Fern cell walls and the evolution of arabinogalactan-proteins in streptophytes. 36891885 9 33 theme monosaccharide 1343:1356 arg1 types 1366:1370 rather conserved monosaccharide linkage types 1326:1370 rather conserved monosaccharide linkage types 1326:1370 Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. 36891885 7 34 theme terminal 942:949 arg1 Ara 963:965 terminal furanosidic Ara 942:965 terminal furanosidic Ara (Araf) 942:972 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 7 34 theme terminal 942:949 arg1 Araf 968:971 Araf 968:971 Araf 968:971 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 10 35 theme AGP 1548:1550 arg1 backbones 1560:1568 AGP protein backbones 1548:1568 AGP protein backbones 1548:1568 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 3 36 gly glycoproteins 479:491 arg1 arabinogalactan-proteins 510:533 the fern arabinogalactan-proteins 501:533 the fern arabinogalactan-proteins (AGPs) 501:540 Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). 36891885 3 36 gly glycoproteins 479:491 arg1 glycoproteins 479:491 glycoproteins 479:491 glycoproteins such as the fern arabinogalactan-proteins (AGPs) 479:540 Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). 36891885 3 37 theme limited 458:464 arg1 knowledge 466:474 limited knowledge 458:474 limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs) 458:540 Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). 36891885 3 38 theme wall 406:409 arg1 composition 411:421 Fern cell wall composition 396:421 Fern cell wall composition 396:421 Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). 36891885 5 39 theme investigated 814:825 arg1 AGPs 832:835 the investigated fern AGPs 810:835 the investigated fern AGPs 810:835 The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. 36891885 11 40 theme AGP 1681:1683 arg1 diversity 1685:1693 AGP diversity 1681:1693 AGP diversity 1681:1693 Our data reveal important differences across AGP diversity which functional significance is unknown. 36891885 2 41 theme evolutionary 370:381 arg1 innovations 383:393 seed plant-specific evolutionary innovations 350:393 seed plant-specific evolutionary innovations 350:393 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 10 42 theme genetic 1591:1597 arg1 toolkit 1599:1605 a versatile genetic toolkit 1579:1605 a versatile genetic toolkit for AGP complexity in ferns 1579:1633 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 2 43 theme seed 350:353 arg1 innovations 383:393 seed plant-specific evolutionary innovations 350:393 seed plant-specific evolutionary innovations 350:393 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 9 44 theme more 1426:1429 arg1 variability 1431:1441 more variability 1426:1441 more variability 1426:1441 Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. 36891885 10 45 from toolkit 1599:1605 arg1 ferns 1629:1633 ferns 1629:1633 ferns 1629:1633 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 5 46 theme seed 674:677 arg1 AGPs 685:688 seed plant AGPs 674:688 seed plant AGPs 674:688 The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. 36891885 5 47 link 1,3,6-linked 748:759 arg1 galactose 773:781 1,3,6-linked pyranosidic galactose 748:781 1,3,6-linked pyranosidic galactose 748:781 The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. 36891885 8 48 theme AGPs 1152:1155 arg1 epitopes 1140:1147 carbohydrate epitopes 1127:1147 carbohydrate epitopes of AGPs 1127:1155 Antibodies directed against carbohydrate epitopes of AGPs supported the structural differences between AGPs of ferns and seed plants. 36891885 6 49 theme unusual 900:906 arg1 3-O-methylrhamnose 914:931 the unusual sugar 3-O-methylrhamnose 896:931 the unusual sugar 3-O-methylrhamnose 896:931 Yet, unlike AGPs of angiosperms, those of ferns contained the unusual sugar 3-O-methylrhamnose. 36891885 12 50 theme cell 1839:1842 arg1 walls 1844:1848 their elaborate cell walls 1823:1848 the hallmark feature of tracheophytes: their elaborate cell walls 1784:1848 This diversity sheds light on the evolution of the hallmark feature of tracheophytes: their elaborate cell walls. 36891885 7 51 from plants 1055:1060 arg1 dominating 1087:1096 dominating 1087:1096 dominating 1087:1096 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 2 52 theme ferns 268:272 arg1 knowledge 238:246 knowledge 238:246 knowledge on the cell wall of ferns 238:272 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 12 53 theme feature 1797:1803 arg1 evolution 1771:1779 the evolution 1767:1779 the evolution of the hallmark feature of tracheophytes: their elaborate cell walls 1767:1848 This diversity sheds light on the evolution of the hallmark feature of tracheophytes: their elaborate cell walls. 36891885 7 54 theme 1,5-linked 1062:1071 arg1 Araf 1073:1076 1,5-linked Araf 1062:1076 1,5-linked Araf 1062:1076 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 12 55 theme tracheophytes 1808:1820 arg1 feature 1797:1803 the hallmark feature 1784:1803 the hallmark feature of tracheophytes: their elaborate cell walls 1784:1848 This diversity sheds light on the evolution of the hallmark feature of tracheophytes: their elaborate cell walls. 36891885 5 56 theme galactan 704:711 arg1 backbone 713:720 a galactan backbone 702:720 a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs 702:835 The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. 36891885 6 57 contain contained 886:894 arg2 3-O-methylrhamnose 914:931 the unusual sugar 3-O-methylrhamnose 896:931 the unusual sugar 3-O-methylrhamnose 896:931 Yet, unlike AGPs of angiosperms, those of ferns contained the unusual sugar 3-O-methylrhamnose. 36891885 6 57 contain contained 886:894 arg1 those 871:875 those 871:875 those 871:875 Yet, unlike AGPs of angiosperms, those of ferns contained the unusual sugar 3-O-methylrhamnose. 36891885 3 58 theme fern 505:508 arg1 AGPs 536:539 AGPs 536:539 AGPs 536:539 Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). 36891885 3 58 theme fern 505:508 arg1 arabinogalactan-proteins 510:533 the fern arabinogalactan-proteins 501:533 the fern arabinogalactan-proteins (AGPs) 501:540 Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). 36891885 4 59 from Ceratopteris 633:644 arg1 AGPs 569:572 the AGPs 565:572 the AGPs from the leptosporangiate fern genera Azolla, Salvinia and Ceratopteris 565:644 Here, we characterize the AGPs from the leptosporangiate fern genera Azolla, Salvinia and Ceratopteris. 36891885 8 60 theme ferns 1210:1214 arg1 AGPs 1202:1205 AGPs 1202:1205 AGPs of ferns and seed plants 1202:1230 Antibodies directed against carbohydrate epitopes of AGPs supported the structural differences between AGPs of ferns and seed plants. 36891885 7 61 from ferns 1012:1016 arg1 type 992:995 the main linkage type 975:995 the main linkage type of Araf in the ferns 975:1016 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 7 61 from ferns 1012:1016 arg1 Araf 1033:1036 1,2-linked Araf 1022:1036 1,2-linked Araf 1022:1036 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 5 62 theme AGPs 685:688 arg1 moiety 664:669 The carbohydrate moiety 647:669 The carbohydrate moiety of seed plant AGPs 647:688 The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. 36891885 9 63 theme AGP 1247:1249 arg1 types 1259:1263 AGP linkage types 1247:1263 AGP linkage types across the streptophyte lineage 1247:1295 Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. 36891885 1 64 theme plant 117:121 arg1 composition 133:143 plant cell wall composition 117:143 plant cell wall composition 117:143 Significant changes have occurred in plant cell wall composition during evolution and diversification of tracheophytes. 36891885 8 65 theme seed 1220:1223 arg1 plants 1225:1230 seed plants 1220:1230 seed plants 1220:1230 Antibodies directed against carbohydrate epitopes of AGPs supported the structural differences between AGPs of ferns and seed plants. 36891885 7 66 theme seed 1050:1053 arg1 plants 1055:1060 seed plants 1050:1060 seed plants 1050:1060 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 9 67 theme types 1259:1263 arg1 Comparison 1233:1242 Comparison 1233:1242 Comparison of AGP linkage types across the streptophyte lineage 1233:1295 Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. 36891885 1 68 theme wall 128:131 arg1 composition 133:143 plant cell wall composition 117:143 plant cell wall composition 117:143 Significant changes have occurred in plant cell wall composition during evolution and diversification of tracheophytes. 36891885 12 69 dep feature 1797:1803 arg1 walls 1844:1848 their elaborate cell walls 1823:1848 the hallmark feature of tracheophytes: their elaborate cell walls 1784:1848 This diversity sheds light on the evolution of the hallmark feature of tracheophytes: their elaborate cell walls. 36891885 7 70 theme linkage 984:990 arg1 type 992:995 the main linkage type 975:995 the main linkage type of Araf in the ferns 975:1016 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 7 70 theme linkage 984:990 arg1 Araf 1033:1036 1,2-linked Araf 1022:1036 1,2-linked Araf 1022:1036 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 10 71 theme glycosyltransferases 1469:1488 arg1 analyses 1457:1464 Phylogenetic analyses 1444:1464 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis 1444:1517 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 10 71 theme glycosyltransferases 1469:1488 arg1 search 1537:1542 bioinformatic search 1523:1542 bioinformatic search for AGP protein backbones 1523:1568 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 5 72 theme 1,3,6-linked 748:759 arg1 galactose 773:781 1,3,6-linked pyranosidic galactose 748:781 1,3,6-linked pyranosidic galactose 748:781 The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. 36891885 0 73 from evolution 24:32 arg1 streptophytes 65:77 streptophytes 65:77 streptophytes 65:77 Fern cell walls and the evolution of arabinogalactan-proteins in streptophytes. 36891885 5 74 theme fern 827:830 arg1 AGPs 832:835 the investigated fern AGPs 810:835 the investigated fern AGPs 810:835 The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. 36891885 9 75 theme conserved 1333:1341 arg1 types 1366:1370 rather conserved monosaccharide linkage types 1326:1370 rather conserved monosaccharide linkage types 1326:1370 Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. 36891885 3 76 theme cell 401:404 arg1 composition 411:421 Fern cell wall composition 396:421 Fern cell wall composition 396:421 Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). 36891885 9 77 theme linkage 1358:1364 arg1 types 1366:1370 rather conserved monosaccharide linkage types 1326:1370 rather conserved monosaccharide linkage types 1326:1370 Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. 36891885 7 78 theme furanosidic 951:961 arg1 Ara 963:965 terminal furanosidic Ara 942:965 terminal furanosidic Ara (Araf) 942:972 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 7 78 theme furanosidic 951:961 arg1 Araf 968:971 Araf 968:971 Araf 968:971 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 9 79 contain have 1321:1324 arg1 angiosperms 1309:1319 angiosperms 1309:1319 angiosperms 1309:1319 Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. 36891885 9 79 contain have 1321:1324 arg2 types 1366:1370 rather conserved monosaccharide linkage types 1326:1370 rather conserved monosaccharide linkage types 1326:1370 Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. 36891885 3 80 theme glycoproteins 479:491 arg1 knowledge 466:474 limited knowledge 458:474 limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs) 458:540 Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). 36891885 7 81 from dominating 1087:1096 arg1 plants 1055:1060 seed plants 1050:1060 seed plants 1050:1060 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 10 82 theme bioinformatic 1523:1535 arg1 search 1537:1542 bioinformatic search 1523:1542 bioinformatic search for AGP protein backbones 1523:1568 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 0 83 theme arabinogalactan-proteins 37:60 arg1 walls 10:14 Fern cell walls 0:14 Fern cell walls 0:14 Fern cell walls and the evolution of arabinogalactan-proteins in streptophytes. 36891885 0 83 theme arabinogalactan-proteins 37:60 arg1 evolution 24:32 the evolution 20:32 the evolution of arabinogalactan-proteins in streptophytes 20:77 Fern cell walls and the evolution of arabinogalactan-proteins in streptophytes. 36891885 6 84 theme angiosperms 858:868 arg1 AGPs 850:853 AGPs 850:853 AGPs of angiosperms 850:868 Yet, unlike AGPs of angiosperms, those of ferns contained the unusual sugar 3-O-methylrhamnose. 36891885 7 85 link 1,2-linked 1022:1031 arg1 Araf 1033:1036 1,2-linked Araf 1022:1036 1,2-linked Araf 1022:1036 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 7 85 link 1,2-linked 1022:1031 arg1 type 992:995 the main linkage type 975:995 the main linkage type of Araf in the ferns 975:1016 Besides terminal furanosidic Ara (Araf), the main linkage type of Araf in the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Araf is often dominating. 36891885 10 86 theme protein 1552:1558 arg1 backbones 1560:1568 AGP protein backbones 1548:1568 AGP protein backbones 1548:1568 Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. 36891885 2 87 theme sister 207:212 arg1 lineage 214:220 the sister lineage 203:220 the sister lineage to seed plants 203:235 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 2 88 theme plant-specific 355:368 arg1 innovations 383:393 seed plant-specific evolutionary innovations 350:393 seed plant-specific evolutionary innovations 350:393 As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. 36891885 8 89 theme carbohydrate 1127:1138 arg1 epitopes 1140:1147 carbohydrate epitopes 1127:1147 carbohydrate epitopes of AGPs 1127:1155 Antibodies directed against carbohydrate epitopes of AGPs supported the structural differences between AGPs of ferns and seed plants. 36891885 11 90 theme functional 1701:1710 arg1 significance 1712:1723 functional significance 1701:1723 functional significance 1701:1723 Our data reveal important differences across AGP diversity which functional significance is unknown. 36891885 11 91 theme important 1652:1660 arg1 differences 1662:1672 important differences 1652:1672 important differences across AGP diversity which functional significance is unknown 1652:1734 Our data reveal important differences across AGP diversity which functional significance is unknown. 36891885 0 92 theme cell 5:8 arg1 walls 10:14 Fern cell walls 0:14 Fern cell walls 0:14 Fern cell walls and the evolution of arabinogalactan-proteins in streptophytes. 35834673 0 0 theme actinomycetes 77:89 arg1 sp 99:100 the marine sponge-associated rare actinomycetes Kocuria sp 43:100 the marine sponge-associated rare actinomycetes Kocuria sp 43:100 An N-N linked dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp. 35834673 2 1 theme derived 115:121 arg1 actinomycetes 128:140 Marine derived rare actinomycetes 108:140 Marine derived rare actinomycetes 108:140 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 0 2 theme rare 72:75 arg1 sp 99:100 the marine sponge-associated rare actinomycetes Kocuria sp 43:100 the marine sponge-associated rare actinomycetes Kocuria sp 43:100 An N-N linked dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp. 35834673 2 3 theme Marine 108:113 arg1 actinomycetes 128:140 Marine derived rare actinomycetes 108:140 Marine derived rare actinomycetes 108:140 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 4 4 theme [1,1'-biindole 408:421 arg1 alkaloid 490:497 a new tryptophan-derived indole alkaloid 458:497 a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp 458:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 4 theme [1,1'-biindole 408:421 arg1 ethane-1,2-diol 440:454 ethane-1,2-diol 440:454 ethane-1,2-diol 440:454 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 4 theme [1,1'-biindole 408:421 arg1 bis 435:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis 402:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol) 402:455 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 6 5 theme spectroscopic 596:608 arg1 analyses 610:617 extensive spectroscopic analyses 586:617 extensive spectroscopic analyses 586:617 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 6 5 theme spectroscopic 596:608 arg1 spectrometry 724:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 6 5 theme spectroscopic 596:608 arg1 resonance 647:655 nuclear magnetic resonance 630:655 nuclear magnetic resonance (NMR) 630:661 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 4 6 theme -3,3'-diyl 423:432 arg1 alkaloid 490:497 a new tryptophan-derived indole alkaloid 458:497 a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp 458:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 6 theme -3,3'-diyl 423:432 arg1 ethane-1,2-diol 440:454 ethane-1,2-diol 440:454 ethane-1,2-diol 440:454 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 6 theme -3,3'-diyl 423:432 arg1 bis 435:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis 402:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol) 402:455 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 3 7 theme special 342:348 arg1 mode 363:366 a special dimerization mode 340:366 a special dimerization mode 340:366 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 3 7 theme special 342:348 arg1 linkage 329:335 N-N linkage 325:335 N-N linkage 325:335 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 4 8 link sponge-derived 515:528 arg1 sp 538:539 the marine sponge-derived Kocuria sp 504:539 the marine sponge-derived Kocuria sp 504:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 6 9 theme extensive 586:594 arg1 analyses 610:617 extensive spectroscopic analyses 586:617 extensive spectroscopic analyses 586:617 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 6 9 theme extensive 586:594 arg1 spectrometry 724:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 6 9 theme extensive 586:594 arg1 resonance 647:655 nuclear magnetic resonance 630:655 nuclear magnetic resonance (NMR) 630:661 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 0 10 theme Kocuria 91:97 arg1 sp 99:100 the marine sponge-associated rare actinomycetes Kocuria sp 43:100 the marine sponge-associated rare actinomycetes Kocuria sp 43:100 An N-N linked dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp. 35834673 6 11 theme mass 707:710 arg1 spectrometry 724:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 4 12 theme new 460:462 arg1 alkaloid 490:497 a new tryptophan-derived indole alkaloid 458:497 a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp 458:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 12 theme new 460:462 arg1 bis 435:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis 402:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol) 402:455 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 3 13 theme Dimeric 237:243 arg1 alkaloids 252:260 Dimeric indole alkaloids 237:260 Dimeric indole alkaloids 237:260 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 6 14 theme ionization 696:705 arg1 spectrometry 724:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 3 15 theme indole 245:250 arg1 alkaloids 252:260 Dimeric indole alkaloids 237:260 Dimeric indole alkaloids 237:260 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 4 16 from sp 538:539 arg1 alkaloid 490:497 a new tryptophan-derived indole alkaloid 458:497 a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp 458:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 16 from sp 538:539 arg1 bis 435:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis 402:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol) 402:455 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 6 17 theme electrospray 683:694 arg1 spectrometry 724:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 7 18 theme indole 754:759 arg1 alkaloid 761:768 The new dimeric indole alkaloid 738:768 The new dimeric indole alkaloid via N-N linkage 738:784 The new dimeric indole alkaloid via N-N linkage exhibits moderate antimicrobial activity. 35834673 3 19 theme N-N 325:327 arg1 mode 363:366 a special dimerization mode 340:366 a special dimerization mode 340:366 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 3 19 theme N-N 325:327 arg1 linkage 329:335 N-N linkage 325:335 N-N linkage 325:335 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 6 20 theme high-resolution 667:681 arg1 spectrometry 724:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 4 21 theme indole 483:488 arg1 alkaloid 490:497 a new tryptophan-derived indole alkaloid 458:497 a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp 458:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 21 theme indole 483:488 arg1 bis 435:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis 402:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol) 402:455 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 22 theme Kocuria 530:536 arg1 sp 538:539 the marine sponge-derived Kocuria sp 504:539 the marine sponge-derived Kocuria sp 504:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 23 theme 1,1'- 402:406 arg1 alkaloid 490:497 a new tryptophan-derived indole alkaloid 458:497 a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp 458:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 23 theme 1,1'- 402:406 arg1 ethane-1,2-diol 440:454 ethane-1,2-diol 440:454 ethane-1,2-diol 440:454 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 23 theme 1,1'- 402:406 arg1 bis 435:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis 402:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol) 402:455 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 0 24 theme dimeric 14:20 arg1 alkaloid 29:36 dimeric indole alkaloid 14:36 dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp 14:100 An N-N linked dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp. 35834673 4 25 link tryptophan-derived 464:481 arg1 alkaloid 490:497 a new tryptophan-derived indole alkaloid 458:497 a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp 458:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 25 link tryptophan-derived 464:481 arg1 bis 435:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis 402:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol) 402:455 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 7 26 theme moderate 795:802 arg1 activity 818:825 moderate antimicrobial activity 795:825 moderate antimicrobial activity 795:825 The new dimeric indole alkaloid via N-N linkage exhibits moderate antimicrobial activity. 35834673 2 27 theme new 168:170 arg1 sources 172:178 the new sources 164:178 the new sources for various natural products for further drug discovery 164:234 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 2 28 theme drug 221:224 arg1 discovery 226:234 further drug discovery 213:234 further drug discovery 213:234 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 0 29 theme indole 22:27 arg1 alkaloid 29:36 dimeric indole alkaloid 14:36 dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp 14:100 An N-N linked dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp. 35834673 4 30 theme bis 435:437 arg1 isolation 389:397 the isolation 385:397 the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp 385:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 2 31 theme further 213:219 arg1 discovery 226:234 further drug discovery 213:234 further drug discovery 213:234 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 7 32 theme N-N 774:776 arg1 linkage 778:784 N-N linkage 774:784 N-N linkage 774:784 The new dimeric indole alkaloid via N-N linkage exhibits moderate antimicrobial activity. 35834673 3 33 theme diverse 296:302 arg1 products 312:319 structurally diverse natural products 283:319 structurally diverse natural products 283:319 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 4 34 theme sponge-derived 515:528 arg1 sp 538:539 the marine sponge-derived Kocuria sp 504:539 the marine sponge-derived Kocuria sp 504:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 3 35 theme products 312:319 arg1 products 312:319 structurally diverse natural products 283:319 structurally diverse natural products 283:319 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 3 35 theme products 312:319 arg1 group 274:278 a group 272:278 a group of structurally diverse natural products 272:319 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 4 36 theme tryptophan-derived 464:481 arg1 alkaloid 490:497 a new tryptophan-derived indole alkaloid 458:497 a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp 458:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 36 theme tryptophan-derived 464:481 arg1 bis 435:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis 402:437 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol) 402:455 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 4 37 theme marine 508:513 arg1 sp 538:539 the marine sponge-derived Kocuria sp 504:539 the marine sponge-derived Kocuria sp 504:539 Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. 35834673 3 38 theme natural 304:310 arg1 products 312:319 structurally diverse natural products 283:319 structurally diverse natural products 283:319 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 2 39 theme natural 192:198 arg1 products 200:207 various natural products 184:207 various natural products 184:207 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 2 40 theme various 184:190 arg1 products 200:207 various natural products 184:207 various natural products 184:207 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 6 41 theme magnetic 638:645 arg1 NMR 658:660 NMR 658:660 NMR 658:660 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 6 41 theme magnetic 638:645 arg1 resonance 647:655 nuclear magnetic resonance 630:655 nuclear magnetic resonance (NMR) 630:661 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 7 42 theme new 742:744 arg1 alkaloid 761:768 The new dimeric indole alkaloid 738:768 The new dimeric indole alkaloid via N-N linkage 738:784 The new dimeric indole alkaloid via N-N linkage exhibits moderate antimicrobial activity. 35834673 0 43 from sp 99:100 arg1 alkaloid 29:36 dimeric indole alkaloid 14:36 dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp 14:100 An N-N linked dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp. 35834673 2 44 link derived 115:121 arg1 actinomycetes 128:140 Marine derived rare actinomycetes 108:140 Marine derived rare actinomycetes 108:140 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 6 45 theme nuclear 630:636 arg1 NMR 658:660 NMR 658:660 NMR 658:660 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 6 45 theme nuclear 630:636 arg1 resonance 647:655 nuclear magnetic resonance 630:655 nuclear magnetic resonance (NMR) 630:661 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 7 46 theme dimeric 746:752 arg1 alkaloid 761:768 The new dimeric indole alkaloid 738:768 The new dimeric indole alkaloid via N-N linkage 738:784 The new dimeric indole alkaloid via N-N linkage exhibits moderate antimicrobial activity. 35834673 0 47 theme sponge-associated 54:70 arg1 sp 99:100 the marine sponge-associated rare actinomycetes Kocuria sp 43:100 the marine sponge-associated rare actinomycetes Kocuria sp 43:100 An N-N linked dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp. 35834673 2 48 theme sources 172:178 arg1 one 157:159 one 157:159 one 157:159 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 2 48 theme sources 172:178 arg1 sources 172:178 the new sources 164:178 the new sources for various natural products for further drug discovery 164:234 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 7 49 theme antimicrobial 804:816 arg1 activity 818:825 moderate antimicrobial activity 795:825 moderate antimicrobial activity 795:825 The new dimeric indole alkaloid via N-N linkage exhibits moderate antimicrobial activity. 35834673 0 50 theme marine 47:52 arg1 sp 99:100 the marine sponge-associated rare actinomycetes Kocuria sp 43:100 the marine sponge-associated rare actinomycetes Kocuria sp 43:100 An N-N linked dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp. 35834673 2 51 theme rare 123:126 arg1 actinomycetes 128:140 Marine derived rare actinomycetes 108:140 Marine derived rare actinomycetes 108:140 Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. 35834673 6 52 theme HR-ESI-MS 713:721 arg1 spectrometry 724:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry 667:735 The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. 35834673 3 53 theme dimerization 350:361 arg1 mode 363:366 a special dimerization mode 340:366 a special dimerization mode 340:366 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 35834673 3 53 theme dimerization 350:361 arg1 linkage 329:335 N-N linkage 325:335 N-N linkage 325:335 Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. 37379686 3 0 with polysaccharides 569:583 arg1 groups 619:624 different pendant functional groups 590:624 different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone 590:677 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 6 1 theme % 1049:1049 arg1 % 1056:1056 16% to 64% 1047:1056 16% to 64% in the copolymers with ε-caprolactone 1047:1094 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 6 2 dep % 1056:1056 arg1 to 1051:1052 to 1051:1052 to 1051:1052 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 3 3 theme functional 608:617 arg1 groups 619:624 different pendant functional groups 590:624 different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone 590:677 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 1 4 theme copolymers 216:225 arg1 synthesis 185:193 the synthesis 181:193 the synthesis of highly functional copolymers from different types of cyclic monomers 181:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 10 5 with copolymers 1855:1864 arg1 applications 1871:1882 applications 1871:1882 applications ranging from sustainable materials to biomaterials 1871:1933 Overall, this work underscores the utility of levoglucosan as a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials. 37379686 8 6 theme copolymer 1408:1416 arg1 microstructure 1418:1431 the copolymer microstructure 1404:1431 the copolymer microstructure 1404:1431 Monomer reactivity ratios were determined to investigate the copolymer microstructure, indicating that levoglucosan-based copolymers have a gradient architecture. 37379686 2 7 theme current 367:373 arg1 polymers 403:410 current fossil-fuel-based synthetic polymers 367:410 current fossil-fuel-based synthetic polymers 367:410 Although copolymers are essential to the plastics industry, environmental concerns associated with current fossil-fuel-based synthetic polymers have led to an increasing interest in the use of renewable feedstock for polymer synthesis. 37379686 1 8 theme different 232:240 arg1 types 242:246 different types 232:246 different types of cyclic monomers 232:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 8 9 theme Monomer 1347:1353 arg1 ratios 1366:1371 Monomer reactivity ratios 1347:1371 Monomer reactivity ratios 1347:1371 Monomer reactivity ratios were determined to investigate the copolymer microstructure, indicating that levoglucosan-based copolymers have a gradient architecture. 37379686 6 10 with copolymers 1118:1127 arg1 levoglucosan 1143:1154 triallyl levoglucosan 1134:1154 triallyl levoglucosan 1134:1154 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 4 11 theme bismuth 761:767 arg1 catalyst 808:815 the optimal catalyst 796:815 the optimal catalyst for cROCOP of levoglucosan 796:842 Biocompatible and recyclable bismuth triflate was identified as the optimal catalyst for cROCOP of levoglucosan. 37379686 4 11 theme bismuth 761:767 arg1 triflate 769:776 Biocompatible and recyclable bismuth triflate 732:776 Biocompatible and recyclable bismuth triflate 732:776 Biocompatible and recyclable bismuth triflate was identified as the optimal catalyst for cROCOP of levoglucosan. 37379686 10 12 theme bioderived 1788:1797 arg1 feedstock 1799:1807 a bioderived feedstock 1786:1807 a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials 1786:1933 Overall, this work underscores the utility of levoglucosan as a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials. 37379686 7 13 theme other 1282:1286 arg1 architectures 1296:1308 other polymer architectures 1282:1308 other polymer architectures 1282:1308 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 1 14 theme monomers 258:265 arg1 types 242:246 different types 232:246 different types of cyclic monomers 232:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 8 15 contain have 1480:1483 arg2 architecture 1496:1507 a gradient architecture 1485:1507 a gradient architecture 1485:1507 Monomer reactivity ratios were determined to investigate the copolymer microstructure, indicating that levoglucosan-based copolymers have a gradient architecture. 37379686 8 15 contain have 1480:1483 arg1 copolymers 1469:1478 levoglucosan-based copolymers 1450:1478 levoglucosan-based copolymers 1450:1478 Monomer reactivity ratios were determined to investigate the copolymer microstructure, indicating that levoglucosan-based copolymers have a gradient architecture. 37379686 7 16 theme allylic 1161:1167 arg1 copolymer 1182:1190 The allylic levoglucosan copolymer 1157:1190 The allylic levoglucosan copolymer 1157:1190 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 7 16 theme allylic 1161:1167 arg1 scaffold 1231:1238 a renewably derived scaffold 1211:1238 a renewably derived scaffold 1211:1238 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 3 17 theme cationic 683:690 arg1 cROCOP 723:728 cROCOP 723:728 cROCOP 723:728 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 3 17 theme cationic 683:690 arg1 copolymerization 705:720 cationic ring-opening copolymerization 683:720 cationic ring-opening copolymerization (cROCOP) 683:729 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 1 18 from types 242:246 arg1 synthesis 185:193 the synthesis 181:193 the synthesis of highly functional copolymers from different types of cyclic monomers 181:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 1 18 from types 242:246 arg1 copolymers 216:225 highly functional copolymers 198:225 highly functional copolymers from different types of cyclic monomers 198:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 1 19 theme powerful 159:166 arg1 strategy 168:175 a powerful strategy 157:175 a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers 157:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 1 19 theme powerful 159:166 arg1 copolymerization 137:152 Simultaneous ring-opening copolymerization 111:152 Simultaneous ring-opening copolymerization 111:152 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 3 20 from levoglucosan 647:658 arg1 groups 619:624 different pendant functional groups 590:624 different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone 590:677 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 3 21 link biomass-derived 631:645 arg1 levoglucosan 647:658 biomass-derived levoglucosan 631:658 biomass-derived levoglucosan 631:658 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 7 22 link derived 1223:1229 arg1 scaffold 1231:1238 a renewably derived scaffold 1211:1238 a renewably derived scaffold 1211:1238 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 7 22 link derived 1223:1229 arg1 copolymer 1182:1190 The allylic levoglucosan copolymer 1157:1190 The allylic levoglucosan copolymer 1157:1190 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 4 23 theme optimal 800:806 arg1 catalyst 808:815 the optimal catalyst 796:815 the optimal catalyst for cROCOP of levoglucosan 796:842 Biocompatible and recyclable bismuth triflate was identified as the optimal catalyst for cROCOP of levoglucosan. 37379686 4 23 theme optimal 800:806 arg1 triflate 769:776 Biocompatible and recyclable bismuth triflate 732:776 Biocompatible and recyclable bismuth triflate 732:776 Biocompatible and recyclable bismuth triflate was identified as the optimal catalyst for cROCOP of levoglucosan. 37379686 3 24 from ε-caprolactone 664:677 arg1 groups 619:624 different pendant functional groups 590:624 different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone 590:677 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 0 25 theme Derivatives 79:89 arg1 Copolymerization 46:61 Cationic Ring-Opening Copolymerization 24:61 Cationic Ring-Opening Copolymerization of Levoglucosan Derivatives and ε-Caprolactone 24:108 Biobased Copolymers via Cationic Ring-Opening Copolymerization of Levoglucosan Derivatives and ε-Caprolactone. 37379686 0 26 theme ε-Caprolactone 95:108 arg1 Copolymerization 46:61 Cationic Ring-Opening Copolymerization 24:61 Cationic Ring-Opening Copolymerization of Levoglucosan Derivatives and ε-Caprolactone 24:108 Biobased Copolymers via Cationic Ring-Opening Copolymerization of Levoglucosan Derivatives and ε-Caprolactone. 37379686 6 27 dep % 1109:1109 arg1 to 1104:1105 to 1104:1105 to 1104:1105 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 3 28 theme scalable 524:531 arg1 platform 543:550 a scalable synthetic platform 522:550 a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP) 522:729 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 1 29 theme ring-opening 124:135 arg1 strategy 168:175 a powerful strategy 157:175 a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers 157:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 1 29 theme ring-opening 124:135 arg1 copolymerization 137:152 Simultaneous ring-opening copolymerization 111:152 Simultaneous ring-opening copolymerization 111:152 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 2 30 theme polymer 485:491 arg1 synthesis 493:501 polymer synthesis 485:501 polymer synthesis 485:501 Although copolymers are essential to the plastics industry, environmental concerns associated with current fossil-fuel-based synthetic polymers have led to an increasing interest in the use of renewable feedstock for polymer synthesis. 37379686 7 31 theme polymer 1288:1294 arg1 architectures 1296:1308 other polymer architectures 1282:1308 other polymer architectures 1282:1308 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 6 32 theme monomer 1015:1021 arg1 composition 1023:1033 The tribenzyl levoglucosan monomer composition 988:1033 The tribenzyl levoglucosan monomer composition 988:1033 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 10 33 theme sugar-based 1843:1853 arg1 copolymers 1855:1864 functional sugar-based copolymers 1832:1864 functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials 1832:1933 Overall, this work underscores the utility of levoglucosan as a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials. 37379686 2 34 theme feedstock 471:479 arg1 use 454:456 the use 450:456 the use of renewable feedstock for polymer synthesis 450:501 Although copolymers are essential to the plastics industry, environmental concerns associated with current fossil-fuel-based synthetic polymers have led to an increasing interest in the use of renewable feedstock for polymer synthesis. 37379686 0 35 theme Ring-Opening 33:44 arg1 Copolymerization 46:61 Cationic Ring-Opening Copolymerization 24:61 Cationic Ring-Opening Copolymerization of Levoglucosan Derivatives and ε-Caprolactone 24:108 Biobased Copolymers via Cationic Ring-Opening Copolymerization of Levoglucosan Derivatives and ε-Caprolactone. 37379686 6 36 theme tribenzyl 992:1000 arg1 composition 1023:1033 The tribenzyl levoglucosan monomer composition 988:1033 The tribenzyl levoglucosan monomer composition 988:1033 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 10 37 theme sustainable 1897:1907 arg1 materials 1909:1917 sustainable materials 1897:1917 sustainable materials 1897:1917 Overall, this work underscores the utility of levoglucosan as a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials. 37379686 9 38 theme glass 1559:1563 arg1 temperature 1576:1586 the copolymer glass transition temperature 1545:1586 the copolymer glass transition temperature (Tg, ranging from -44.3 to 33.8 °C) 1545:1622 Additionally, we demonstrated that the copolymer glass transition temperature (Tg, ranging from -44.3 to 33.8 °C), thermal stability, and crystallization behavior could be tuned based on the copolymer composition. 37379686 3 39 theme synthetic 533:541 arg1 platform 543:550 a scalable synthetic platform 522:550 a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP) 522:729 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 10 40 theme functional 1832:1841 arg1 copolymers 1855:1864 functional sugar-based copolymers 1832:1864 functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials 1832:1933 Overall, this work underscores the utility of levoglucosan as a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials. 37379686 0 41 theme Levoglucosan 66:77 arg1 Derivatives 79:89 Levoglucosan Derivatives 66:89 Levoglucosan Derivatives 66:89 Biobased Copolymers via Cationic Ring-Opening Copolymerization of Levoglucosan Derivatives and ε-Caprolactone. 37379686 6 42 from % 1056:1056 arg1 copolymers 1065:1074 the copolymers 1061:1074 the copolymers with ε-caprolactone 1061:1094 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 6 42 from % 1056:1056 arg1 copolymers 1118:1127 the copolymers 1114:1127 the copolymers with triallyl levoglucosan 1114:1154 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 3 43 theme unique 562:567 arg1 polysaccharides 569:583 unique polysaccharides 562:583 unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone 562:677 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 7 44 theme derived 1223:1229 arg1 scaffold 1231:1238 a renewably derived scaffold 1211:1238 a renewably derived scaffold 1211:1238 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 7 44 theme derived 1223:1229 arg1 copolymer 1182:1190 The allylic levoglucosan copolymer 1157:1190 The allylic levoglucosan copolymer 1157:1190 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 7 45 used utilized 1199:1206 arg2 copolymer 1182:1190 The allylic levoglucosan copolymer 1157:1190 The allylic levoglucosan copolymer 1157:1190 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 7 45 used utilized 1199:1206 arg2 scaffold 1231:1238 a renewably derived scaffold 1211:1238 a renewably derived scaffold 1211:1238 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 3 46 theme pendant 600:606 arg1 groups 619:624 different pendant functional groups 590:624 different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone 590:677 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 1 47 theme functional 205:214 arg1 copolymers 216:225 highly functional copolymers 198:225 highly functional copolymers from different types of cyclic monomers 198:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 5 48 dep tribenzyl 920:928 arg1 levoglucosan 943:954 levoglucosan 943:954 levoglucosan 943:954 Copolymers from tribenzyl levoglucosan and ε-caprolactone, as well as from tribenzyl and triallyl levoglucosan, were successfully synthesized. 37379686 10 49 theme levoglucosan 1770:1781 arg1 utility 1759:1765 the utility 1755:1765 the utility of levoglucosan as a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials 1755:1933 Overall, this work underscores the utility of levoglucosan as a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials. 37379686 2 50 theme fossil-fuel-based 375:391 arg1 polymers 403:410 current fossil-fuel-based synthetic polymers 367:410 current fossil-fuel-based synthetic polymers 367:410 Although copolymers are essential to the plastics industry, environmental concerns associated with current fossil-fuel-based synthetic polymers have led to an increasing interest in the use of renewable feedstock for polymer synthesis. 37379686 6 51 theme % 1102:1102 arg1 % 1109:1109 22% to 79% 1100:1109 22% to 79% in the copolymers with triallyl levoglucosan 1100:1154 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 2 52 from interest 438:445 arg1 use 454:456 the use 450:456 the use of renewable feedstock for polymer synthesis 450:501 Although copolymers are essential to the plastics industry, environmental concerns associated with current fossil-fuel-based synthetic polymers have led to an increasing interest in the use of renewable feedstock for polymer synthesis. 37379686 10 53 link bioderived 1788:1797 arg1 feedstock 1799:1807 a bioderived feedstock 1786:1807 a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials 1786:1933 Overall, this work underscores the utility of levoglucosan as a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials. 37379686 3 54 theme biomass-derived 631:645 arg1 levoglucosan 647:658 biomass-derived levoglucosan 631:658 biomass-derived levoglucosan 631:658 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 9 55 theme thermal 1625:1631 arg1 stability 1633:1641 thermal stability 1625:1641 thermal stability 1625:1641 Additionally, we demonstrated that the copolymer glass transition temperature (Tg, ranging from -44.3 to 33.8 °C), thermal stability, and crystallization behavior could be tuned based on the copolymer composition. 37379686 6 56 with copolymers 1065:1074 arg1 ε-caprolactone 1081:1094 ε-caprolactone 1081:1094 ε-caprolactone 1081:1094 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 4 57 theme Biocompatible 732:744 arg1 catalyst 808:815 the optimal catalyst 796:815 the optimal catalyst for cROCOP of levoglucosan 796:842 Biocompatible and recyclable bismuth triflate was identified as the optimal catalyst for cROCOP of levoglucosan. 37379686 4 57 theme Biocompatible 732:744 arg1 triflate 769:776 Biocompatible and recyclable bismuth triflate 732:776 Biocompatible and recyclable bismuth triflate 732:776 Biocompatible and recyclable bismuth triflate was identified as the optimal catalyst for cROCOP of levoglucosan. 37379686 7 58 theme levoglucosan 1169:1180 arg1 copolymer 1182:1190 The allylic levoglucosan copolymer 1157:1190 The allylic levoglucosan copolymer 1157:1190 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 7 58 theme levoglucosan 1169:1180 arg1 scaffold 1231:1238 a renewably derived scaffold 1211:1238 a renewably derived scaffold 1211:1238 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 5 59 from levoglucosan 871:882 arg1 Copolymers 845:854 Copolymers 845:854 Copolymers from tribenzyl levoglucosan and ε-caprolactone, as well as from tribenzyl and triallyl levoglucosan, 845:955 Copolymers from tribenzyl levoglucosan and ε-caprolactone, as well as from tribenzyl and triallyl levoglucosan, were successfully synthesized. 37379686 3 60 theme ring-opening 692:703 arg1 cROCOP 723:728 cROCOP 723:728 cROCOP 723:728 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 3 60 theme ring-opening 692:703 arg1 copolymerization 705:720 cationic ring-opening copolymerization 683:720 cationic ring-opening copolymerization (cROCOP) 683:729 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 37379686 1 61 theme cyclic 251:256 arg1 monomers 258:265 cyclic monomers 251:265 cyclic monomers 251:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 8 62 theme reactivity 1355:1364 arg1 ratios 1366:1371 Monomer reactivity ratios 1347:1371 Monomer reactivity ratios 1347:1371 Monomer reactivity ratios were determined to investigate the copolymer microstructure, indicating that levoglucosan-based copolymers have a gradient architecture. 37379686 9 63 dep temperature 1576:1586 arg1 Tg 1589:1590 Tg 1589:1590 Tg 1589:1590 Additionally, we demonstrated that the copolymer glass transition temperature (Tg, ranging from -44.3 to 33.8 °C), thermal stability, and crystallization behavior could be tuned based on the copolymer composition. 37379686 4 64 theme recyclable 750:759 arg1 catalyst 808:815 the optimal catalyst 796:815 the optimal catalyst for cROCOP of levoglucosan 796:842 Biocompatible and recyclable bismuth triflate was identified as the optimal catalyst for cROCOP of levoglucosan. 37379686 4 64 theme recyclable 750:759 arg1 triflate 769:776 Biocompatible and recyclable bismuth triflate 732:776 Biocompatible and recyclable bismuth triflate 732:776 Biocompatible and recyclable bismuth triflate was identified as the optimal catalyst for cROCOP of levoglucosan. 37379686 9 65 theme crystallization 1648:1662 arg1 behavior 1664:1671 crystallization behavior 1648:1671 crystallization behavior 1648:1671 Additionally, we demonstrated that the copolymer glass transition temperature (Tg, ranging from -44.3 to 33.8 °C), thermal stability, and crystallization behavior could be tuned based on the copolymer composition. 37379686 8 66 theme levoglucosan-based 1450:1467 arg1 copolymers 1469:1478 levoglucosan-based copolymers 1450:1478 levoglucosan-based copolymers 1450:1478 Monomer reactivity ratios were determined to investigate the copolymer microstructure, indicating that levoglucosan-based copolymers have a gradient architecture. 37379686 2 67 theme plastics 309:316 arg1 industry 318:325 the plastics industry 305:325 the plastics industry 305:325 Although copolymers are essential to the plastics industry, environmental concerns associated with current fossil-fuel-based synthetic polymers have led to an increasing interest in the use of renewable feedstock for polymer synthesis. 37379686 6 68 theme triallyl 1134:1141 arg1 levoglucosan 1143:1154 triallyl levoglucosan 1134:1154 triallyl levoglucosan 1134:1154 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 4 69 theme levoglucosan 831:842 arg1 cROCOP 821:826 cROCOP 821:826 cROCOP of levoglucosan 821:842 Biocompatible and recyclable bismuth triflate was identified as the optimal catalyst for cROCOP of levoglucosan. 37379686 8 70 theme gradient 1487:1494 arg1 architecture 1496:1507 a gradient architecture 1485:1507 a gradient architecture 1485:1507 Monomer reactivity ratios were determined to investigate the copolymer microstructure, indicating that levoglucosan-based copolymers have a gradient architecture. 37379686 5 71 from tribenzyl 920:928 arg1 Copolymers 845:854 Copolymers 845:854 Copolymers from tribenzyl levoglucosan and ε-caprolactone, as well as from tribenzyl and triallyl levoglucosan, 845:955 Copolymers from tribenzyl levoglucosan and ε-caprolactone, as well as from tribenzyl and triallyl levoglucosan, were successfully synthesized. 37379686 2 72 dep environmental 328:340 arg1 concerns 342:349 concerns 342:349 concerns 342:349 Although copolymers are essential to the plastics industry, environmental concerns associated with current fossil-fuel-based synthetic polymers have led to an increasing interest in the use of renewable feedstock for polymer synthesis. 37379686 9 73 theme copolymer 1701:1709 arg1 composition 1711:1721 the copolymer composition 1697:1721 the copolymer composition 1697:1721 Additionally, we demonstrated that the copolymer glass transition temperature (Tg, ranging from -44.3 to 33.8 °C), thermal stability, and crystallization behavior could be tuned based on the copolymer composition. 37379686 5 74 theme tribenzyl 861:869 arg1 levoglucosan 871:882 tribenzyl levoglucosan 861:882 tribenzyl levoglucosan 861:882 Copolymers from tribenzyl levoglucosan and ε-caprolactone, as well as from tribenzyl and triallyl levoglucosan, were successfully synthesized. 37379686 1 75 from synthesis 185:193 arg1 types 242:246 different types 232:246 different types of cyclic monomers 232:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 7 76 theme postpolymerization 1314:1331 arg1 modification 1333:1344 postpolymerization modification 1314:1344 postpolymerization modification 1314:1344 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 5 77 from triallyl 934:941 arg1 Copolymers 845:854 Copolymers 845:854 Copolymers from tribenzyl levoglucosan and ε-caprolactone, as well as from tribenzyl and triallyl levoglucosan, 845:955 Copolymers from tribenzyl levoglucosan and ε-caprolactone, as well as from tribenzyl and triallyl levoglucosan, were successfully synthesized. 37379686 1 78 theme Simultaneous 111:122 arg1 strategy 168:175 a powerful strategy 157:175 a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers 157:265 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 1 78 theme Simultaneous 111:122 arg1 copolymerization 137:152 Simultaneous ring-opening copolymerization 111:152 Simultaneous ring-opening copolymerization 111:152 Simultaneous ring-opening copolymerization is a powerful strategy for the synthesis of highly functional copolymers from different types of cyclic monomers. 37379686 6 79 from % 1109:1109 arg1 copolymers 1065:1074 the copolymers 1061:1074 the copolymers with ε-caprolactone 1061:1094 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 6 79 from % 1109:1109 arg1 copolymers 1118:1127 the copolymers 1114:1127 the copolymers with triallyl levoglucosan 1114:1154 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 0 80 theme Cationic 24:31 arg1 Copolymerization 46:61 Cationic Ring-Opening Copolymerization 24:61 Cationic Ring-Opening Copolymerization of Levoglucosan Derivatives and ε-Caprolactone 24:108 Biobased Copolymers via Cationic Ring-Opening Copolymerization of Levoglucosan Derivatives and ε-Caprolactone. 37379686 10 81 theme copolymers 1855:1864 arg1 development 1817:1827 the development 1813:1827 the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials 1813:1933 Overall, this work underscores the utility of levoglucosan as a bioderived feedstock for the development of functional sugar-based copolymers with applications ranging from sustainable materials to biomaterials. 37379686 6 82 theme levoglucosan 1002:1013 arg1 composition 1023:1033 The tribenzyl levoglucosan monomer composition 988:1033 The tribenzyl levoglucosan monomer composition 988:1033 The tribenzyl levoglucosan monomer composition ranged from 16% to 64% in the copolymers with ε-caprolactone and 22% to 79% in the copolymers with triallyl levoglucosan. 37379686 2 83 theme renewable 461:469 arg1 feedstock 471:479 renewable feedstock 461:479 renewable feedstock 461:479 Although copolymers are essential to the plastics industry, environmental concerns associated with current fossil-fuel-based synthetic polymers have led to an increasing interest in the use of renewable feedstock for polymer synthesis. 37379686 7 84 theme copolymer 1250:1258 arg1 properties 1260:1269 copolymer properties 1250:1269 copolymer properties 1250:1269 The allylic levoglucosan copolymer can be utilized as a renewably derived scaffold to modify copolymer properties and create other polymer architectures via postpolymerization modification. 37379686 9 85 theme copolymer 1549:1557 arg1 temperature 1576:1586 the copolymer glass transition temperature 1545:1586 the copolymer glass transition temperature (Tg, ranging from -44.3 to 33.8 °C) 1545:1622 Additionally, we demonstrated that the copolymer glass transition temperature (Tg, ranging from -44.3 to 33.8 °C), thermal stability, and crystallization behavior could be tuned based on the copolymer composition. 37379686 2 86 theme increasing 427:436 arg1 interest 438:445 an increasing interest 424:445 an increasing interest in the use of renewable feedstock for polymer synthesis 424:501 Although copolymers are essential to the plastics industry, environmental concerns associated with current fossil-fuel-based synthetic polymers have led to an increasing interest in the use of renewable feedstock for polymer synthesis. 37379686 9 87 theme transition 1565:1574 arg1 temperature 1576:1586 the copolymer glass transition temperature 1545:1586 the copolymer glass transition temperature (Tg, ranging from -44.3 to 33.8 °C) 1545:1622 Additionally, we demonstrated that the copolymer glass transition temperature (Tg, ranging from -44.3 to 33.8 °C), thermal stability, and crystallization behavior could be tuned based on the copolymer composition. 37379686 2 88 theme synthetic 393:401 arg1 polymers 403:410 current fossil-fuel-based synthetic polymers 367:410 current fossil-fuel-based synthetic polymers 367:410 Although copolymers are essential to the plastics industry, environmental concerns associated with current fossil-fuel-based synthetic polymers have led to an increasing interest in the use of renewable feedstock for polymer synthesis. 37379686 3 89 theme different 590:598 arg1 groups 619:624 different pendant functional groups 590:624 different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone 590:677 Herein, we report a scalable synthetic platform to afford unique polysaccharides with different pendant functional groups from biomass-derived levoglucosan and ε-caprolactone via cationic ring-opening copolymerization (cROCOP). 35327223 2 0 theme transformed 521:531 arg1 infrared 533:540 Fourier transformed infrared 513:540 Fourier transformed infrared (FT-IR) 513:548 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 0 theme transformed 521:531 arg1 FT-IR 543:547 FT-IR 543:547 FT-IR 543:547 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 5 1 theme composition 772:782 arg1 Analysis 741:748 Analysis 741:748 Analysis of the monosaccharide composition 741:782 Analysis of the monosaccharide composition revealed that CYP was primarily comprised of galactose (Gal), glucose (Glu), and galacturonic acid (GalA), and the ratio between them was 28.57:11.28:37.59. 35327223 1 2 theme Rhizoma 151:157 arg1 CYP 176:178 CYP 176:178 CYP 176:178 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 1 2 theme Rhizoma 151:157 arg1 polysaccharide 160:173 Chinese yam (Dioscoreae Rhizoma) polysaccharide 127:173 Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) 127:179 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 8 3 contain has 1402:1404 arg2 prospects 1411:1419 good prospects 1406:1419 good prospects 1406:1419 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 8 3 contain has 1402:1404 arg1 it 1394:1395 it 1394:1395 it 1394:1395 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 1 4 theme oxidative 243:251 arg1 damage 253:258 H2O2-induced oxidative damage 230:258 H2O2-induced oxidative damage in IEC-6 cells 230:273 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 2 5 theme Fourier 513:519 arg1 infrared 533:540 Fourier transformed infrared 513:540 Fourier transformed infrared (FT-IR) 513:548 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 5 theme Fourier 513:519 arg1 FT-IR 543:547 FT-IR 543:547 FT-IR 543:547 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 4 6 theme molecular 702:710 arg1 kDa 736:738 20.89 kDa 730:738 20.89 kDa 730:738 The molecular weight of CYP was 20.89 kDa. 35327223 4 6 theme molecular 702:710 arg1 weight 712:717 The molecular weight 698:717 The molecular weight of CYP 698:724 The molecular weight of CYP was 20.89 kDa. 35327223 8 7 with heteropolysaccharide 1313:1332 arg1 effect 1357:1362 a good protective effect 1339:1362 a good protective effect against oxidative damage 1339:1387 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 2 8 theme chemical 280:287 arg1 composition 289:299 The chemical composition 276:299 The chemical composition 276:299 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 8 9 theme acidic 1306:1311 arg1 CYP 1295:1297 CYP 1295:1297 CYP 1295:1297 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 8 9 theme acidic 1306:1311 arg1 heteropolysaccharide 1313:1332 an acidic heteropolysaccharide 1303:1332 an acidic heteropolysaccharide with a good protective effect against oxidative damage 1303:1387 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 1 10 theme IEC-6 263:267 arg1 cells 269:273 IEC-6 cells 263:273 IEC-6 cells 263:273 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 7 11 theme protein 1231:1237 arg1 MAPK 1247:1250 MAPK 1247:1250 MAPK 1247:1250 CYP also attenuated oxidative damage in cells through the mitogen-activated protein kinase (MAPK) signaling pathway. 35327223 7 11 theme protein 1231:1237 arg1 kinase 1239:1244 mitogen-activated protein kinase 1213:1244 the mitogen-activated protein kinase (MAPK) signaling pathway 1209:1269 CYP also attenuated oxidative damage in cells through the mitogen-activated protein kinase (MAPK) signaling pathway. 35327223 6 12 theme dismutase 1010:1018 arg1 activity 1026:1033 superoxide dismutase (SOD) activity 999:1033 superoxide dismutase (SOD) activity 999:1033 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 6 12 theme dismutase 1010:1018 arg1 viability 988:996 cell viability 983:996 cell viability 983:996 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 6 13 with Pretreatment 941:952 arg1 CYP 959:961 CYP 959:961 CYP 959:961 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 1 14 theme polysaccharide 160:173 arg1 structure 114:122 the structure 110:122 the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) 110:179 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 6 15 theme species 1077:1083 arg1 production 1091:1100 intracellular reactive oxygen species (ROS) production 1047:1100 intracellular reactive oxygen species (ROS) production 1047:1100 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 7 16 theme signaling 1253:1261 arg1 pathway 1263:1269 the mitogen-activated protein kinase (MAPK) signaling pathway 1209:1269 the mitogen-activated protein kinase (MAPK) signaling pathway 1209:1269 CYP also attenuated oxidative damage in cells through the mitogen-activated protein kinase (MAPK) signaling pathway. 35327223 8 17 theme good 1406:1409 arg1 prospects 1411:1419 good prospects 1406:1419 good prospects 1406:1419 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 6 18 theme malondialdehyde 1106:1120 arg1 content 1128:1134 malondialdehyde (MDA) content 1106:1134 malondialdehyde (MDA) content after H2O2 injury 1106:1152 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 7 19 theme mitogen-activated 1213:1229 arg1 MAPK 1247:1250 MAPK 1247:1250 MAPK 1247:1250 CYP also attenuated oxidative damage in cells through the mitogen-activated protein kinase (MAPK) signaling pathway. 35327223 7 19 theme mitogen-activated 1213:1229 arg1 kinase 1239:1244 mitogen-activated protein kinase 1213:1244 the mitogen-activated protein kinase (MAPK) signaling pathway 1209:1269 CYP also attenuated oxidative damage in cells through the mitogen-activated protein kinase (MAPK) signaling pathway. 35327223 2 20 theme anion-exchange 474:487 arg1 HPAEC 505:509 HPAEC 505:509 HPAEC 505:509 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 20 theme anion-exchange 474:487 arg1 chromatography 489:502 high-performance anion-exchange chromatography 457:502 high-performance anion-exchange chromatography (HPAEC) 457:510 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 21 theme structural 305:314 arg1 characteristics 316:330 structural characteristics 305:330 structural characteristics 305:330 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 22 theme instrumental 377:388 arg1 ultraviolet 551:561 ultraviolet 551:561 ultraviolet (UV) 551:566 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 22 theme instrumental 377:388 arg1 chromatography 489:502 high-performance anion-exchange chromatography 457:502 high-performance anion-exchange chromatography (HPAEC) 457:510 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 22 theme instrumental 377:388 arg1 microscopy 591:600 scanning electron microscopy 573:600 scanning electron microscopy (SEM) 573:606 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 22 theme instrumental 377:388 arg1 infrared 533:540 Fourier transformed infrared 513:540 Fourier transformed infrared (FT-IR) 513:548 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 22 theme instrumental 377:388 arg1 chromatography 441:454 high-performance gel permeation chromatography 409:454 high-performance gel permeation chromatography 409:454 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 22 theme instrumental 377:388 arg1 methods 390:396 chemical and instrumental methods 364:396 chemical and instrumental methods 364:396 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 23 theme high-performance 457:472 arg1 HPAEC 505:509 HPAEC 505:509 HPAEC 505:509 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 23 theme high-performance 457:472 arg1 chromatography 489:502 high-performance anion-exchange chromatography 457:502 high-performance anion-exchange chromatography (HPAEC) 457:510 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 6 24 theme H2O2 1142:1145 arg1 injury 1147:1152 H2O2 injury 1142:1152 H2O2 injury 1142:1152 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 8 25 theme protective 1346:1355 arg1 effect 1357:1362 a good protective effect 1339:1362 a good protective effect against oxidative damage 1339:1387 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 6 26 theme superoxide 999:1008 arg1 dismutase 1010:1018 superoxide dismutase 999:1018 superoxide dismutase (SOD) activity 999:1033 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 6 26 theme superoxide 999:1008 arg1 SOD 1021:1023 SOD 1021:1023 SOD 1021:1023 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 6 27 theme oxygen 1070:1075 arg1 species 1077:1083 reactive oxygen species 1061:1083 intracellular reactive oxygen species (ROS) production 1047:1100 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 6 27 theme oxygen 1070:1075 arg1 ROS 1086:1088 ROS 1086:1088 ROS 1086:1088 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 2 28 theme permeation 430:439 arg1 chromatography 441:454 high-performance gel permeation chromatography 409:454 high-performance gel permeation chromatography 409:454 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 7 29 theme kinase 1239:1244 arg1 pathway 1263:1269 the mitogen-activated protein kinase (MAPK) signaling pathway 1209:1269 the mitogen-activated protein kinase (MAPK) signaling pathway 1209:1269 CYP also attenuated oxidative damage in cells through the mitogen-activated protein kinase (MAPK) signaling pathway. 35327223 3 30 theme cellular 662:669 arg1 model 671:675 a cellular model 660:675 a cellular model of oxidative damage 660:695 Antioxidant activity was evaluated by establishing a cellular model of oxidative damage. 35327223 8 31 theme good 1341:1344 arg1 effect 1357:1362 a good protective effect 1339:1362 a good protective effect against oxidative damage 1339:1387 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 2 32 theme gel 426:428 arg1 chromatography 441:454 high-performance gel permeation chromatography 409:454 high-performance gel permeation chromatography 409:454 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 0 33 theme Antioxidant 32:42 arg1 Activity 44:51 Antioxidant Activity 32:51 Antioxidant Activity 32:51 Isolation, Characterization and Antioxidant Activity of Yam Polysaccharides. 35327223 1 34 from damage 253:258 arg1 cells 269:273 IEC-6 cells 263:273 IEC-6 cells 263:273 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 2 35 theme high-performance 409:424 arg1 chromatography 441:454 high-performance gel permeation chromatography 409:454 high-performance gel permeation chromatography 409:454 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 0 36 theme Yam 56:58 arg1 Polysaccharides 60:74 Yam Polysaccharides 56:74 Yam Polysaccharides 56:74 Isolation, Characterization and Antioxidant Activity of Yam Polysaccharides. 35327223 5 37 theme monosaccharide 757:770 arg1 composition 772:782 the monosaccharide composition 753:782 the monosaccharide composition 753:782 Analysis of the monosaccharide composition revealed that CYP was primarily comprised of galactose (Gal), glucose (Glu), and galacturonic acid (GalA), and the ratio between them was 28.57:11.28:37.59. 35327223 6 38 theme reactive 1061:1068 arg1 species 1077:1083 reactive oxygen species 1061:1083 intracellular reactive oxygen species (ROS) production 1047:1100 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 6 38 theme reactive 1061:1068 arg1 ROS 1086:1088 ROS 1086:1088 ROS 1086:1088 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 4 39 theme CYP 722:724 arg1 kDa 736:738 20.89 kDa 730:738 20.89 kDa 730:738 The molecular weight of CYP was 20.89 kDa. 35327223 4 39 theme CYP 722:724 arg1 weight 712:717 The molecular weight 698:717 The molecular weight of CYP 698:724 The molecular weight of CYP was 20.89 kDa. 35327223 2 40 theme electron 582:589 arg1 SEM 603:605 SEM 603:605 SEM 603:605 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 40 theme electron 582:589 arg1 microscopy 591:600 scanning electron microscopy 573:600 scanning electron microscopy (SEM) 573:606 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 3 41 theme oxidative 680:688 arg1 damage 690:695 oxidative damage 680:695 oxidative damage 680:695 Antioxidant activity was evaluated by establishing a cellular model of oxidative damage. 35327223 1 42 theme Dioscoreae 140:149 arg1 CYP 176:178 CYP 176:178 CYP 176:178 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 1 42 theme Dioscoreae 140:149 arg1 polysaccharide 160:173 Chinese yam (Dioscoreae Rhizoma) polysaccharide 127:173 Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) 127:179 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 2 43 theme samples 339:345 arg1 composition 289:299 The chemical composition 276:299 The chemical composition 276:299 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 43 theme samples 339:345 arg1 characteristics 316:330 structural characteristics 305:330 structural characteristics 305:330 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 44 theme scanning 573:580 arg1 SEM 603:605 SEM 603:605 SEM 603:605 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 44 theme scanning 573:580 arg1 microscopy 591:600 scanning electron microscopy 573:600 scanning electron microscopy (SEM) 573:606 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 3 45 theme damage 690:695 arg1 model 671:675 a cellular model 660:675 a cellular model of oxidative damage 660:695 Antioxidant activity was evaluated by establishing a cellular model of oxidative damage. 35327223 8 46 theme oxidative 1372:1380 arg1 damage 1382:1387 oxidative damage 1372:1387 oxidative damage 1372:1387 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 1 47 theme Chinese 127:133 arg1 CYP 176:178 CYP 176:178 CYP 176:178 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 1 47 theme Chinese 127:133 arg1 polysaccharide 160:173 Chinese yam (Dioscoreae Rhizoma) polysaccharide 127:173 Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) 127:179 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 1 48 theme protective 204:213 arg1 effect 215:220 its protective effect 200:220 its protective effect against H2O2-induced oxidative damage in IEC-6 cells 200:273 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 8 49 theme food 1424:1427 arg1 industries 1451:1460 food and biopharmaceutical industries 1424:1460 food and biopharmaceutical industries 1424:1460 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 1 50 theme yam 135:137 arg1 CYP 176:178 CYP 176:178 CYP 176:178 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 1 50 theme yam 135:137 arg1 polysaccharide 160:173 Chinese yam (Dioscoreae Rhizoma) polysaccharide 127:173 Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) 127:179 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 35327223 6 51 theme cell 983:986 arg1 activity 1026:1033 superoxide dismutase (SOD) activity 999:1033 superoxide dismutase (SOD) activity 999:1033 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 6 51 theme cell 983:986 arg1 viability 988:996 cell viability 983:996 cell viability 983:996 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 6 52 theme intracellular 1047:1059 arg1 production 1091:1100 intracellular reactive oxygen species (ROS) production 1047:1100 intracellular reactive oxygen species (ROS) production 1047:1100 Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. 35327223 3 53 theme Antioxidant 609:619 arg1 activity 621:628 Antioxidant activity 609:628 Antioxidant activity 609:628 Antioxidant activity was evaluated by establishing a cellular model of oxidative damage. 35327223 5 54 theme galacturonic 865:876 arg1 acid 878:881 galacturonic acid 865:881 galacturonic acid (GalA) 865:888 Analysis of the monosaccharide composition revealed that CYP was primarily comprised of galactose (Gal), glucose (Glu), and galacturonic acid (GalA), and the ratio between them was 28.57:11.28:37.59. 35327223 5 54 theme galacturonic 865:876 arg1 GalA 884:887 GalA 884:887 GalA 884:887 Analysis of the monosaccharide composition revealed that CYP was primarily comprised of galactose (Gal), glucose (Glu), and galacturonic acid (GalA), and the ratio between them was 28.57:11.28:37.59. 35327223 7 55 theme oxidative 1175:1183 arg1 damage 1185:1190 oxidative damage 1175:1190 oxidative damage 1175:1190 CYP also attenuated oxidative damage in cells through the mitogen-activated protein kinase (MAPK) signaling pathway. 35327223 0 56 theme Polysaccharides 60:74 arg1 Characterization 11:26 Characterization 11:26 Characterization 11:26 Isolation, Characterization and Antioxidant Activity of Yam Polysaccharides. 35327223 0 56 theme Polysaccharides 60:74 arg1 Activity 44:51 Antioxidant Activity 32:51 Antioxidant Activity 32:51 Isolation, Characterization and Antioxidant Activity of Yam Polysaccharides. 35327223 0 56 theme Polysaccharides 60:74 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation, Characterization and Antioxidant Activity of Yam Polysaccharides. 35327223 8 57 theme biopharmaceutical 1433:1449 arg1 industries 1451:1460 food and biopharmaceutical industries 1424:1460 food and biopharmaceutical industries 1424:1460 This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries. 35327223 2 58 theme chemical 364:371 arg1 ultraviolet 551:561 ultraviolet 551:561 ultraviolet (UV) 551:566 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 58 theme chemical 364:371 arg1 chromatography 489:502 high-performance anion-exchange chromatography 457:502 high-performance anion-exchange chromatography (HPAEC) 457:510 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 58 theme chemical 364:371 arg1 microscopy 591:600 scanning electron microscopy 573:600 scanning electron microscopy (SEM) 573:606 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 58 theme chemical 364:371 arg1 infrared 533:540 Fourier transformed infrared 513:540 Fourier transformed infrared (FT-IR) 513:548 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 58 theme chemical 364:371 arg1 chromatography 441:454 high-performance gel permeation chromatography 409:454 high-performance gel permeation chromatography 409:454 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 2 58 theme chemical 364:371 arg1 methods 390:396 chemical and instrumental methods 364:396 chemical and instrumental methods 364:396 The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). 35327223 1 59 theme H2O2-induced 230:241 arg1 damage 253:258 H2O2-induced oxidative damage 230:258 H2O2-induced oxidative damage in IEC-6 cells 230:273 This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. 36111438 3 0 theme colon 653:657 arg1 length 659:664 colon length 653:664 colon length 653:664 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 8 1 theme myeloperoxidase 1943:1957 arg1 expression 1861:1870 mRNA expression 1856:1870 mRNA expression 1856:1870 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 8 1 theme myeloperoxidase 1943:1957 arg1 contents 1884:1891 protein contents 1876:1891 protein contents 1876:1891 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 5 2 theme short 1181:1185 arg1 SCFAs 1206:1210 SCFAs 1206:1210 SCFAs 1206:1210 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 5 2 theme short 1181:1185 arg1 acids 1199:1203 short chain fatty acids 1181:1203 short chain fatty acids (SCFAs) 1181:1211 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 5 3 theme fatty 1193:1197 arg1 SCFAs 1206:1210 SCFAs 1206:1210 SCFAs 1206:1210 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 5 3 theme fatty 1193:1197 arg1 acids 1199:1203 short chain fatty acids 1181:1203 short chain fatty acids (SCFAs) 1181:1211 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 6 4 dep expression 1462:1471 arg1 the 1453:1455 the 1453:1455 the 1453:1455 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 8 5 theme TGF-β2 1827:1832 arg1 expression 1794:1803 the mRNA expression 1785:1803 the mRNA expression of IL-10, TGF-β1, and TGF-β2 1785:1832 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 6 6 theme VCAM 1398:1401 arg1 expression 1373:1382 the mRNA expression 1364:1382 the mRNA expression of ICAM-1 and VCAM 1364:1401 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 6 7 theme protein 1495:1501 arg1 content 1503:1509 immunofluorescent protein content 1477:1509 immunofluorescent protein content 1477:1509 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 1 8 theme ulcerative 192:201 arg1 colitis 203:209 ulcerative colitis 192:209 ulcerative colitis (UC) 192:214 Probiotics have shown good efficacy in the prevention of ulcerative colitis (UC), but the specific mechanism remains unclear. 36111438 1 8 theme ulcerative 192:201 arg1 UC 212:213 UC 212:213 UC 212:213 Probiotics have shown good efficacy in the prevention of ulcerative colitis (UC), but the specific mechanism remains unclear. 36111438 10 9 theme microbiota 2205:2214 arg1 dysbiosis 2216:2224 gut microbiota dysbiosis 2201:2224 gut microbiota dysbiosis 2201:2224 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 9 10 theme disease 2046:2052 arg1 pathways 2017:2024 the metabolic pathways 2003:2024 the metabolic pathways of inflammation and disease in mice 2003:2060 In addition, Lp082 can also regulate the metabolic pathways of inflammation and disease in mice, and notably, Lp082 inhibits the NF-κB signaling pathway by inhibiting NF-κB signaling molecules to alleviate UC. 36111438 3 11 theme immune 701:706 arg1 index 714:718 immune organ index 701:718 immune organ index 701:718 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 7 12 theme claudin-2 1614:1622 arg1 expression 1586:1595 the mRNA expression 1577:1595 the mRNA expression of claudin-1 and claudin-2 1577:1622 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 4 13 theme mucosal 879:885 arg1 barrier 887:893 the intestinal mucosal barrier 864:893 the intestinal mucosal barrier 864:893 The mechanism is deeply studied and it is discovered that Lp082 improves the intestinal mucosal barrier by co-optimizing biological barriers, chemical barriers, mechanical barriers, and immune barriers. 36111438 7 14 theme ZO-1 1725:1728 arg1 expression 1652:1661 the mRNA expression 1643:1661 the mRNA expression of ZO-1 and ZO-2 1643:1678 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 7 14 theme ZO-1 1725:1728 arg1 content 1714:1720 the immunofluorescent protein content 1684:1720 the immunofluorescent protein content of ZO-1 1684:1728 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 11 15 theme probiotic 2705:2713 arg1 prevention 2715:2724 the future probiotic prevention 2694:2724 the future probiotic prevention of human colitis 2694:2741 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 6 16 theme mRNA 1457:1460 arg1 expression 1462:1471 mRNA expression 1457:1471 mRNA expression 1457:1471 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 7 17 theme claudin-1 1600:1608 arg1 expression 1586:1595 the mRNA expression 1577:1595 the mRNA expression of claudin-1 and claudin-2 1577:1622 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 11 18 theme new 2469:2471 arg1 prospect 2473:2480 a new prospect 2467:2480 a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis 2467:2544 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 3 19 theme inflammatory 721:732 arg1 factors 734:740 inflammatory factors 721:740 inflammatory factors 721:740 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 11 20 dep enriches 2431:2438 arg1 provides 2547:2554 provides 2547:2554 provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC 2547:2665 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 10 21 theme inflammatory 2281:2292 arg1 pathways 2306:2313 inflammatory and disease pathways 2281:2313 pathways 2306:2313 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 0 22 from colitis 84:90 arg1 mice 95:98 mice 95:98 mice 95:98 Lactobacillus plantarum HNU082 alleviates dextran sulfate sodium-induced ulcerative colitis in mice through regulating gut microbiome. 36111438 11 23 theme alternative 2628:2638 arg1 strategy 2651:2658 an alternative prevention strategy 2625:2658 an alternative prevention strategy for UC 2625:2665 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 8 24 theme protein 1876:1882 arg1 contents 1884:1891 protein contents 1876:1891 protein contents 1876:1891 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 7 25 theme protein 1706:1712 arg1 content 1714:1720 the immunofluorescent protein content 1684:1720 the immunofluorescent protein content of ZO-1 1684:1728 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 11 26 theme plantarum 2500:2508 arg1 HNU082 2510:2515 Lactobacillus plantarum HNU082 2486:2515 Lactobacillus plantarum HNU082 2486:2515 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 3 27 theme -induced 548:555 arg1 UC 557:558 dextran sulfate sodium (DSS)-induced UC 520:558 dextran sulfate sodium (DSS)-induced UC 520:558 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 1 28 theme good 157:160 arg1 efficacy 162:169 good efficacy 157:169 good efficacy in the prevention of ulcerative colitis (UC) 157:214 Probiotics have shown good efficacy in the prevention of ulcerative colitis (UC), but the specific mechanism remains unclear. 36111438 9 29 theme signaling 2139:2147 arg1 molecules 2149:2157 NF-κB signaling molecules 2133:2157 NF-κB signaling molecules 2133:2157 In addition, Lp082 can also regulate the metabolic pathways of inflammation and disease in mice, and notably, Lp082 inhibits the NF-κB signaling pathway by inhibiting NF-κB signaling molecules to alleviate UC. 36111438 5 30 theme species 1090:1096 arg1 composition 1098:1108 the species composition 1086:1108 the species composition 1086:1108 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 8 31 theme immune 1756:1761 arg1 barrier 1763:1769 the immune barrier 1752:1769 the immune barrier 1752:1769 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 7 32 theme ZO-2 1675:1678 arg1 expression 1652:1661 the mRNA expression 1643:1661 the mRNA expression of ZO-1 and ZO-2 1643:1678 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 7 32 theme ZO-2 1675:1678 arg1 content 1714:1720 the immunofluorescent protein content 1684:1720 the immunofluorescent protein content of ZO-1 1684:1728 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 7 33 theme mechanical 1544:1553 arg1 barrier 1555:1561 the mechanical barrier 1540:1561 the mechanical barrier 1540:1561 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 4 34 theme mechanical 952:961 arg1 barriers 963:970 mechanical barriers 952:970 mechanical barriers 952:970 The mechanism is deeply studied and it is discovered that Lp082 improves the intestinal mucosal barrier by co-optimizing biological barriers, chemical barriers, mechanical barriers, and immune barriers. 36111438 6 35 theme chemical 1333:1340 arg1 barrier 1342:1348 the chemical barrier 1329:1348 the chemical barrier 1329:1348 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 7 36 theme ZO-1 1666:1669 arg1 expression 1652:1661 the mRNA expression 1643:1661 the mRNA expression of ZO-1 and ZO-2 1643:1678 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 7 36 theme ZO-1 1666:1669 arg1 content 1714:1720 the immunofluorescent protein content 1684:1720 the immunofluorescent protein content of ZO-1 1684:1728 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 4 37 theme biological 912:921 arg1 barriers 923:930 biological barriers 912:930 biological barriers 912:930 The mechanism is deeply studied and it is discovered that Lp082 improves the intestinal mucosal barrier by co-optimizing biological barriers, chemical barriers, mechanical barriers, and immune barriers. 36111438 5 38 theme microbial 1229:1237 arg1 pathways 1249:1256 microbial metabolic pathways 1229:1256 microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs 1229:1310 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 3 39 theme Lp082 777:781 arg1 intake 783:788 Lp082 intake 777:788 Lp082 intake 777:788 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 6 40 dep optimized 1319:1327 arg1 increasing 1410:1419 increasing 1410:1419 increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2 1410:1519 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 6 40 dep optimized 1319:1327 arg1 decreasing 1353:1362 decreasing 1353:1362 decreasing the mRNA expression of ICAM-1 and VCAM 1353:1401 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 1 41 from efficacy 162:169 arg1 prevention 178:187 the prevention 174:187 the prevention of ulcerative colitis (UC) 174:214 Probiotics have shown good efficacy in the prevention of ulcerative colitis (UC), but the specific mechanism remains unclear. 36111438 9 42 from pathways 2017:2024 arg1 mice 2057:2060 mice 2057:2060 mice 2057:2060 In addition, Lp082 can also regulate the metabolic pathways of inflammation and disease in mice, and notably, Lp082 inhibits the NF-κB signaling pathway by inhibiting NF-κB signaling molecules to alleviate UC. 36111438 5 43 theme SCFAs 1306:1310 arg1 content 1295:1301 the content 1291:1301 the content of SCFAs 1291:1310 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 2 44 theme plantarum 406:414 arg1 HNU082 416:421 a potential probiotic Lactobacillus plantarum HNU082 370:421 a potential probiotic Lactobacillus plantarum HNU082 (Lp082) 370:429 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 2 44 theme plantarum 406:414 arg1 Lp082 424:428 Lp082 424:428 Lp082 424:428 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 0 45 theme Lactobacillus 0:12 arg1 HNU082 24:29 Lactobacillus plantarum HNU082 0:29 Lactobacillus plantarum HNU082 0:29 Lactobacillus plantarum HNU082 alleviates dextran sulfate sodium-induced ulcerative colitis in mice through regulating gut microbiome. 36111438 5 46 theme microbiota 1139:1148 arg1 composition 1098:1108 the species composition 1086:1108 the species composition 1086:1108 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 5 46 theme microbiota 1139:1148 arg1 structure 1118:1126 the structure 1114:1126 the structure of the gut microbiota 1114:1148 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 5 47 theme biological 1027:1036 arg1 barrier 1038:1044 the biological barrier 1023:1044 the biological barrier 1023:1044 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 8 48 theme IL-10 1808:1812 arg1 expression 1794:1803 the mRNA expression 1785:1803 the mRNA expression of IL-10, TGF-β1, and TGF-β2 1785:1832 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 6 49 theme ICAM-1 1387:1392 arg1 expression 1373:1382 the mRNA expression 1364:1382 the mRNA expression of ICAM-1 and VCAM 1364:1401 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 10 50 theme potential 2362:2370 arg1 mechanisms 2372:2381 the potential mechanisms 2358:2381 the potential mechanisms of probiotic Lp082 in alleviating UC 2358:2418 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 11 51 theme colitis 2735:2741 arg1 prevention 2715:2724 the future probiotic prevention 2694:2724 the future probiotic prevention of human colitis 2694:2741 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 0 52 theme dextran 42:48 arg1 sulfate 50:56 dextran sulfate 42:56 dextran sulfate sodium-induced ulcerative colitis in mice 42:98 Lactobacillus plantarum HNU082 alleviates dextran sulfate sodium-induced ulcerative colitis in mice through regulating gut microbiome. 36111438 10 53 theme Lp082 2396:2400 arg1 mechanisms 2372:2381 the potential mechanisms 2358:2381 the potential mechanisms of probiotic Lp082 in alleviating UC 2358:2418 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 4 54 theme immune 977:982 arg1 barriers 984:991 immune barriers 977:991 immune barriers 977:991 The mechanism is deeply studied and it is discovered that Lp082 improves the intestinal mucosal barrier by co-optimizing biological barriers, chemical barriers, mechanical barriers, and immune barriers. 36111438 11 55 theme products 2613:2620 arg1 development 2572:2582 the development 2568:2582 the development of probiotic-based microbial products as an alternative prevention strategy for UC 2568:2665 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 3 56 theme water 622:626 arg1 intake 628:633 water intake 622:633 water intake 622:633 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 0 57 theme sodium-induced 58:71 arg1 colitis 84:90 dextran sulfate sodium-induced ulcerative colitis 42:90 dextran sulfate sodium-induced ulcerative colitis in mice 42:98 Lactobacillus plantarum HNU082 alleviates dextran sulfate sodium-induced ulcerative colitis in mice through regulating gut microbiome. 36111438 11 58 theme probiotic-based 2587:2601 arg1 products 2613:2620 probiotic-based microbial products 2587:2620 probiotic-based microbial products as an alternative prevention strategy for UC 2587:2665 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 9 59 theme metabolic 2007:2015 arg1 pathways 2017:2024 the metabolic pathways 2003:2024 the metabolic pathways of inflammation and disease in mice 2003:2060 In addition, Lp082 can also regulate the metabolic pathways of inflammation and disease in mice, and notably, Lp082 inhibits the NF-κB signaling pathway by inhibiting NF-κB signaling molecules to alleviate UC. 36111438 6 60 theme cells 1443:1447 arg1 expression 1462:1471 mRNA expression 1457:1471 mRNA expression 1457:1471 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 6 60 theme cells 1443:1447 arg1 content 1425:1431 the content 1421:1431 the content of goblet cells 1421:1447 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 6 60 theme cells 1443:1447 arg1 content 1503:1509 immunofluorescent protein content 1477:1509 immunofluorescent protein content 1477:1509 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 2 61 theme shotgun 272:278 arg1 analyses 310:317 shotgun metagenomic and transcriptome analyses 272:317 shotgun metagenomic and transcriptome analyses 272:317 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 8 62 dep optimized 1742:1750 arg1 increasing 1774:1783 increasing 1774:1783 increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 1774:1832 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 8 62 dep optimized 1742:1750 arg1 decreasing 1841:1850 decreasing 1841:1850 decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) 1841:1963 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 2 63 theme probiotic 382:390 arg1 HNU082 416:421 a potential probiotic Lactobacillus plantarum HNU082 370:421 a potential probiotic Lactobacillus plantarum HNU082 (Lp082) 370:429 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 2 63 theme probiotic 382:390 arg1 Lp082 424:428 Lp082 424:428 Lp082 424:428 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 6 64 theme mRNA 1368:1371 arg1 expression 1373:1382 the mRNA expression 1364:1382 the mRNA expression of ICAM-1 and VCAM 1364:1401 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 10 65 theme disease 2298:2304 arg1 pathways 2306:2313 inflammatory and disease pathways 2281:2313 pathways 2306:2313 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 8 66 theme TGF-β1 1815:1820 arg1 expression 1794:1803 the mRNA expression 1785:1803 the mRNA expression of IL-10, TGF-β1, and TGF-β2 1785:1832 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 2 67 theme transcriptome 296:308 arg1 analyses 310:317 shotgun metagenomic and transcriptome analyses 272:317 shotgun metagenomic and transcriptome analyses 272:317 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 5 68 theme chain 1187:1191 arg1 SCFAs 1206:1210 SCFAs 1206:1210 SCFAs 1206:1210 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 5 68 theme chain 1187:1191 arg1 acids 1199:1203 short chain fatty acids 1181:1203 short chain fatty acids (SCFAs) 1181:1211 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 2 69 from effect 360:365 arg1 mechanism 454:462 its specific mechanism 441:462 its specific mechanism 441:462 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 2 69 from effect 360:365 arg1 UC 434:435 UC 434:435 UC 434:435 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 11 70 theme colitis 2538:2544 arg1 prevention 2524:2533 the prevention 2520:2533 the prevention of colitis 2520:2544 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 3 71 theme DAI 690:692 arg1 index 694:698 the DAI index 686:698 the DAI index 686:698 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 2 72 theme metagenomic 280:290 arg1 analyses 310:317 shotgun metagenomic and transcriptome analyses 272:317 shotgun metagenomic and transcriptome analyses 272:317 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 3 73 from decrease 674:681 arg1 scores 764:769 histopathological scores 746:769 histopathological scores after Lp082 intake 746:788 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 73 from decrease 674:681 arg1 index 714:718 immune organ index 701:718 immune organ index 701:718 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 73 from decrease 674:681 arg1 intake 628:633 water intake 622:633 water intake 622:633 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 73 from decrease 674:681 arg1 length 659:664 colon length 653:664 colon length 653:664 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 73 from decrease 674:681 arg1 factors 734:740 inflammatory factors 721:740 inflammatory factors 721:740 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 73 from decrease 674:681 arg1 index 694:698 the DAI index 686:698 the DAI index 686:698 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 73 from decrease 674:681 arg1 weight 614:619 body weight 609:619 body weight 609:619 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 73 from decrease 674:681 arg1 intake 641:646 food intake 636:646 food intake 636:646 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 8 74 theme necrosis 1909:1916 arg1 TNF-α 1932:1936 TNF-α 1932:1936 TNF-α 1932:1936 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 8 74 theme necrosis 1909:1916 arg1 factor-alpha 1918:1929 tumour necrosis factor-alpha 1902:1929 tumour necrosis factor-alpha (TNF-α) 1902:1937 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 6 75 theme immunofluorescent 1477:1493 arg1 content 1503:1509 immunofluorescent protein content 1477:1509 immunofluorescent protein content 1477:1509 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 1 76 theme colitis 203:209 arg1 prevention 178:187 the prevention 174:187 the prevention of ulcerative colitis (UC) 174:214 Probiotics have shown good efficacy in the prevention of ulcerative colitis (UC), but the specific mechanism remains unclear. 36111438 10 77 theme gut 2201:2203 arg1 dysbiosis 2216:2224 gut microbiota dysbiosis 2201:2224 gut microbiota dysbiosis 2201:2224 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 10 78 theme alleviating 2405:2415 arg1 UC 2417:2418 alleviating UC 2405:2418 alleviating UC 2405:2418 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 3 79 theme organ 708:712 arg1 index 714:718 immune organ index 701:718 immune organ index 701:718 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 8 80 theme mRNA 1856:1859 arg1 expression 1861:1870 mRNA expression 1856:1870 mRNA expression 1856:1870 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 4 81 theme intestinal 868:877 arg1 barrier 887:893 the intestinal mucosal barrier 864:893 the intestinal mucosal barrier 864:893 The mechanism is deeply studied and it is discovered that Lp082 improves the intestinal mucosal barrier by co-optimizing biological barriers, chemical barriers, mechanical barriers, and immune barriers. 36111438 7 82 theme mRNA 1581:1584 arg1 expression 1586:1595 the mRNA expression 1577:1595 the mRNA expression of claudin-1 and claudin-2 1577:1622 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 11 83 theme future 2698:2703 arg1 prevention 2715:2724 the future probiotic prevention 2694:2724 the future probiotic prevention of human colitis 2694:2741 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 9 84 theme signaling 2101:2109 arg1 pathway 2111:2117 the NF-κB signaling pathway 2091:2117 the NF-κB signaling pathway 2091:2117 In addition, Lp082 can also regulate the metabolic pathways of inflammation and disease in mice, and notably, Lp082 inhibits the NF-κB signaling pathway by inhibiting NF-κB signaling molecules to alleviate UC. 36111438 10 85 theme mucosal 2253:2259 arg1 barrier 2261:2267 the intestinal mucosal barrier 2238:2267 the intestinal mucosal barrier 2238:2267 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 11 86 theme Lactobacillus 2486:2498 arg1 HNU082 2510:2515 Lactobacillus plantarum HNU082 2486:2515 Lactobacillus plantarum HNU082 2486:2515 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 11 87 theme prevention 2640:2649 arg1 strategy 2651:2658 an alternative prevention strategy 2625:2658 an alternative prevention strategy for UC 2625:2665 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 5 88 theme metabolic 1239:1247 arg1 pathways 1249:1256 microbial metabolic pathways 1229:1256 microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs 1229:1310 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 8 89 theme IL-6 1896:1899 arg1 expression 1861:1870 mRNA expression 1856:1870 mRNA expression 1856:1870 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 8 89 theme IL-6 1896:1899 arg1 contents 1884:1891 protein contents 1876:1891 protein contents 1876:1891 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 3 90 theme body 609:612 arg1 weight 614:619 body weight 609:619 body weight 609:619 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 9 91 theme NF-κB 2133:2137 arg1 molecules 2149:2157 NF-κB signaling molecules 2133:2157 NF-κB signaling molecules 2133:2157 In addition, Lp082 can also regulate the metabolic pathways of inflammation and disease in mice, and notably, Lp082 inhibits the NF-κB signaling pathway by inhibiting NF-κB signaling molecules to alleviate UC. 36111438 8 92 theme tumour 1902:1907 arg1 TNF-α 1932:1936 TNF-α 1932:1936 TNF-α 1932:1936 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 8 92 theme tumour 1902:1907 arg1 factor-alpha 1918:1929 tumour necrosis factor-alpha 1902:1929 tumour necrosis factor-alpha (TNF-α) 1902:1937 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 7 93 dep ameliorated 1528:1538 arg1 decreasing 1566:1575 decreasing 1566:1575 decreasing the mRNA expression of claudin-1 and claudin-2 1566:1622 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 7 93 dep ameliorated 1528:1538 arg1 increasing 1632:1641 increasing 1632:1641 increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1 1632:1728 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 7 94 theme immunofluorescent 1688:1704 arg1 content 1714:1720 the immunofluorescent protein content 1684:1720 the immunofluorescent protein content of ZO-1 1684:1728 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 4 95 theme chemical 933:940 arg1 barriers 942:949 chemical barriers 933:949 chemical barriers 933:949 The mechanism is deeply studied and it is discovered that Lp082 improves the intestinal mucosal barrier by co-optimizing biological barriers, chemical barriers, mechanical barriers, and immune barriers. 36111438 3 96 theme histopathological 746:762 arg1 scores 764:769 histopathological scores 746:769 histopathological scores after Lp082 intake 746:788 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 8 97 theme factor-alpha 1918:1929 arg1 expression 1861:1870 mRNA expression 1856:1870 mRNA expression 1856:1870 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 8 97 theme factor-alpha 1918:1929 arg1 contents 1884:1891 protein contents 1876:1891 protein contents 1876:1891 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 6 98 theme mucin2 1514:1519 arg1 expression 1462:1471 mRNA expression 1457:1471 mRNA expression 1457:1471 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 6 98 theme mucin2 1514:1519 arg1 content 1425:1431 the content 1421:1431 the content of goblet cells 1421:1447 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 6 98 theme mucin2 1514:1519 arg1 content 1503:1509 immunofluorescent protein content 1477:1509 immunofluorescent protein content 1477:1509 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 10 99 theme intestinal 2242:2251 arg1 barrier 2261:2267 the intestinal mucosal barrier 2238:2267 the intestinal mucosal barrier 2238:2267 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 10 100 from mechanisms 2372:2381 arg1 conclusion 2179:2188 conclusion 2179:2188 conclusion 2179:2188 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 10 100 from mechanisms 2372:2381 arg1 UC 2417:2418 alleviating UC 2405:2418 alleviating UC 2405:2418 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 0 101 theme gut 119:121 arg1 microbiome 123:132 gut microbiome 119:132 gut microbiome 119:132 Lactobacillus plantarum HNU082 alleviates dextran sulfate sodium-induced ulcerative colitis in mice through regulating gut microbiome. 36111438 10 102 theme neutrophil 2330:2339 arg1 infiltration 2341:2352 neutrophil infiltration 2330:2352 neutrophil infiltration 2330:2352 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 3 103 from increase 597:604 arg1 scores 764:769 histopathological scores 746:769 histopathological scores after Lp082 intake 746:788 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 103 from increase 597:604 arg1 index 714:718 immune organ index 701:718 immune organ index 701:718 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 103 from increase 597:604 arg1 intake 628:633 water intake 622:633 water intake 622:633 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 103 from increase 597:604 arg1 length 659:664 colon length 653:664 colon length 653:664 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 103 from increase 597:604 arg1 factors 734:740 inflammatory factors 721:740 inflammatory factors 721:740 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 103 from increase 597:604 arg1 index 694:698 the DAI index 686:698 the DAI index 686:698 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 103 from increase 597:604 arg1 weight 614:619 body weight 609:619 body weight 609:619 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 103 from increase 597:604 arg1 intake 641:646 food intake 636:646 food intake 636:646 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 2 104 theme HNU082 416:421 arg1 effect 360:365 the preventive effect 345:365 the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism 345:462 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 0 105 theme plantarum 14:22 arg1 HNU082 24:29 Lactobacillus plantarum HNU082 0:29 Lactobacillus plantarum HNU082 0:29 Lactobacillus plantarum HNU082 alleviates dextran sulfate sodium-induced ulcerative colitis in mice through regulating gut microbiome. 36111438 8 106 theme mRNA 1789:1792 arg1 expression 1794:1803 the mRNA expression 1785:1803 the mRNA expression of IL-10, TGF-β1, and TGF-β2 1785:1832 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 7 107 theme mRNA 1647:1650 arg1 expression 1652:1661 the mRNA expression 1643:1661 the mRNA expression of ZO-1 and ZO-2 1643:1678 Lp082 ameliorated the mechanical barrier by decreasing the mRNA expression of claudin-1 and claudin-2, and by increasing the mRNA expression of ZO-1 and ZO-2 and the immunofluorescent protein content of ZO-1. 36111438 2 108 theme specific 445:452 arg1 mechanism 454:462 its specific mechanism 441:462 its specific mechanism 441:462 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 2 109 theme Lactobacillus 392:404 arg1 HNU082 416:421 a potential probiotic Lactobacillus plantarum HNU082 370:421 a potential probiotic Lactobacillus plantarum HNU082 (Lp082) 370:429 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 2 109 theme Lactobacillus 392:404 arg1 Lp082 424:428 Lp082 424:428 Lp082 424:428 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 10 110 theme probiotic 2386:2394 arg1 Lp082 2396:2400 probiotic Lp082 2386:2400 probiotic Lp082 2386:2400 In conclusion, improving gut microbiota dysbiosis, protecting the intestinal mucosal barrier, regulating inflammatory and disease pathways, and affecting neutrophil infiltration are the potential mechanisms of probiotic Lp082 in alleviating UC. 36111438 0 111 theme sulfate 50:56 arg1 colitis 84:90 dextran sulfate sodium-induced ulcerative colitis 42:90 dextran sulfate sodium-induced ulcerative colitis in mice 42:98 Lactobacillus plantarum HNU082 alleviates dextran sulfate sodium-induced ulcerative colitis in mice through regulating gut microbiome. 36111438 8 112 dep expression 1861:1870 arg1 the 1852:1854 the 1852:1854 the 1852:1854 Lp082 also optimized the immune barrier by increasing the mRNA expression of IL-10, TGF-β1, and TGF-β2 and by decreasing the mRNA expression and protein contents of IL-6, tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO). 36111438 11 113 theme microbial 2603:2611 arg1 products 2613:2620 probiotic-based microbial products 2587:2620 probiotic-based microbial products as an alternative prevention strategy for UC 2587:2665 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 0 114 theme ulcerative 73:82 arg1 colitis 84:90 dextran sulfate sodium-induced ulcerative colitis 42:90 dextran sulfate sodium-induced ulcerative colitis in mice 42:98 Lactobacillus plantarum HNU082 alleviates dextran sulfate sodium-induced ulcerative colitis in mice through regulating gut microbiome. 36111438 9 115 theme NF-κB 2095:2099 arg1 pathway 2111:2117 the NF-κB signaling pathway 2091:2117 the NF-κB signaling pathway 2091:2117 In addition, Lp082 can also regulate the metabolic pathways of inflammation and disease in mice, and notably, Lp082 inhibits the NF-κB signaling pathway by inhibiting NF-κB signaling molecules to alleviate UC. 36111438 11 116 theme human 2729:2733 arg1 colitis 2735:2741 human colitis 2729:2741 human colitis 2729:2741 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 2 117 theme preventive 349:358 arg1 effect 360:365 the preventive effect 345:365 the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism 345:462 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 5 118 theme gut 1135:1137 arg1 microbiota 1139:1148 the gut microbiota 1131:1148 the gut microbiota 1131:1148 Specifically, Lp082 improved the biological barrier by increasing the diversity, optimizing the species composition and the structure of the gut microbiota, increasing bacteria producing short chain fatty acids (SCFAs), and activating microbial metabolic pathways producing SCFAs so as to enhance the content of SCFAs. 36111438 3 119 theme food 636:639 arg1 intake 641:646 food intake 636:646 food intake 636:646 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 3 120 theme Lp082 489:493 arg1 intervention 495:506 Lp082 intervention 489:506 Lp082 intervention 489:506 The results showed that Lp082 intervention ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested in the increase in body weight, water intake, food intake, and colon length and the decrease in the DAI index, immune organ index, inflammatory factors and histopathological scores after Lp082 intake. 36111438 6 121 theme goblet 1436:1441 arg1 cells 1443:1447 goblet cells 1436:1447 goblet cells 1436:1447 Lp082 optimized the chemical barrier by decreasing the mRNA expression of ICAM-1 and VCAM and by increasing the content of goblet cells and the mRNA expression and immunofluorescent protein content of mucin2. 36111438 1 122 theme specific 225:232 arg1 mechanism 234:242 the specific mechanism 221:242 the specific mechanism 221:242 Probiotics have shown good efficacy in the prevention of ulcerative colitis (UC), but the specific mechanism remains unclear. 36111438 11 123 from prospect 2473:2480 arg1 prevention 2524:2533 the prevention 2520:2533 the prevention of colitis 2520:2544 Our study enriches the mechanism and provides a new prospect for Lactobacillus plantarum HNU082 in the prevention of colitis, provides support for the development of probiotic-based microbial products as an alternative prevention strategy for UC, and provides guidance for the future probiotic prevention of human colitis. 36111438 9 124 theme inflammation 2029:2040 arg1 pathways 2017:2024 the metabolic pathways 2003:2024 the metabolic pathways of inflammation and disease in mice 2003:2060 In addition, Lp082 can also regulate the metabolic pathways of inflammation and disease in mice, and notably, Lp082 inhibits the NF-κB signaling pathway by inhibiting NF-κB signaling molecules to alleviate UC. 36111438 2 125 theme potential 372:380 arg1 HNU082 416:421 a potential probiotic Lactobacillus plantarum HNU082 370:421 a potential probiotic Lactobacillus plantarum HNU082 (Lp082) 370:429 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36111438 2 125 theme potential 372:380 arg1 Lp082 424:428 Lp082 424:428 Lp082 424:428 Therefore, shotgun metagenomic and transcriptome analyses were performed to explore the preventive effect of a potential probiotic Lactobacillus plantarum HNU082 (Lp082) on UC and its specific mechanism. 36539686 7 0 theme wall 1165:1168 arg1 component 1170:1178 a single cell wall component 1151:1178 a single cell wall component 1151:1178 CONCLUSIONS The action of a single cell wall component does not elicit any influence ex situ. 36539686 2 1 from influence 395:403 arg1 activity 413:420 this activity 408:420 this activity 408:420 The aim of the current study was to investigate the antifungal effect of AGPs ex situ and to determine the structural features of AGPs that may have an influence on this activity. 36539686 6 2 theme functional 1043:1052 arg1 properties 1054:1063 the same functional properties 1034:1063 the same functional properties outside the plant cell 1034:1086 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 0 3 theme carbohydrate 60:71 arg1 composition 73:83 carbohydrate composition 60:83 carbohydrate composition 60:83 Working towards arabinogalactan proteins (AGPs) from fruit: carbohydrate composition and impact on fungal growth. 36539686 6 4 contain have 1029:1032 arg1 JIM13 1009:1013 JIM13 1009:1013 JIM13 1009:1013 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 6 4 contain have 1029:1032 arg2 properties 1054:1063 the same functional properties 1034:1063 the same functional properties outside the plant cell 1034:1086 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 0 5 from impact 89:94 arg1 growth 106:111 fungal growth 99:111 fungal growth 99:111 Working towards arabinogalactan proteins (AGPs) from fruit: carbohydrate composition and impact on fungal growth. 36539686 8 6 from chains 1256:1261 arg1 tissue 1283:1288 infected tissue 1274:1288 infected tissue 1274:1288 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 6 7 theme same 1038:1041 arg1 properties 1054:1063 the same functional properties 1034:1063 the same functional properties outside the plant cell 1034:1086 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 6 8 theme -GalA-α 976:982 arg1 Rha 991:993 GlcA-β(1 → 3)-GalA-α(1 → 2) Rha 963:993 GlcA-β(1 → 3)-GalA-α(1 → 2) Rha 963:993 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 7 9 theme single 1153:1158 arg1 component 1170:1178 a single cell wall component 1151:1178 a single cell wall component 1151:1178 CONCLUSIONS The action of a single cell wall component does not elicit any influence ex situ. 36539686 8 10 theme cell 1342:1345 arg1 wall 1347:1350 the cell wall 1338:1350 the cell wall 1338:1350 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 8 11 theme complex 1307:1313 arg1 mechanism 1315:1323 a complex mechanism 1305:1323 a complex mechanism occurring in the cell wall 1305:1350 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 4 12 theme notatum 715:721 arg1 culture 723:729 Penicillium notatum culture 703:729 Penicillium notatum culture 703:729 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 36539686 6 13 theme carbohydrate 878:889 arg1 chains 891:896 carbohydrate chains 878:896 carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions 878:1122 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 3 14 theme specific 512:519 arg1 antibodies 532:541 specific monoclonal antibodies 512:541 specific monoclonal antibodies recognizing carbohydrate AGP epitopes 512:579 The features of AGPs isolated from fruit were investigated with molecular tools based on specific monoclonal antibodies recognizing carbohydrate AGP epitopes. 36539686 4 15 theme AGPs 695:698 arg1 impact 685:690 the impact 681:690 the impact of AGPs on Penicillium notatum culture 681:729 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 36539686 0 16 theme fungal 99:104 arg1 growth 106:111 fungal growth 99:111 fungal growth 99:111 Working towards arabinogalactan proteins (AGPs) from fruit: carbohydrate composition and impact on fungal growth. 36539686 6 17 dep in 1091:1092 arg1 vitro 1094:1098 vitro 1094:1098 vitro 1094:1098 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 2 18 theme study 266:270 arg1 aim 247:249 The aim 243:249 The aim of the current study 243:270 The aim of the current study was to investigate the antifungal effect of AGPs ex situ and to determine the structural features of AGPs that may have an influence on this activity. 36539686 6 19 link β-linked 910:917 arg1 residues 932:939 β-linked glucuronosyl residues 910:939 β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions 910:1122 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 2 20 theme AGPs 373:376 arg1 features 361:368 the structural features 346:368 the structural features of AGPs that may have an influence on this activity 346:420 The aim of the current study was to investigate the antifungal effect of AGPs ex situ and to determine the structural features of AGPs that may have an influence on this activity. 36539686 6 21 theme 1 → 3 970:974 arg1 Rha 991:993 GlcA-β(1 → 3)-GalA-α(1 → 2) Rha 963:993 GlcA-β(1 → 3)-GalA-α(1 → 2) Rha 963:993 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 6 22 theme GlcA-β 963:968 arg1 Rha 991:993 GlcA-β(1 → 3)-GalA-α(1 → 2) Rha 963:993 GlcA-β(1 → 3)-GalA-α(1 → 2) Rha 963:993 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 2 23 theme current 258:264 arg1 study 266:270 the current study 254:270 the current study 254:270 The aim of the current study was to investigate the antifungal effect of AGPs ex situ and to determine the structural features of AGPs that may have an influence on this activity. 36539686 1 24 theme extracellular 161:173 arg1 constituents 182:193 extracellular matrix constituents 161:193 extracellular matrix constituents involved in plant response to fungal infection 161:240 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 1 24 theme extracellular 161:173 arg1 proteins 141:148 BACKGROUND Arabinogalactan proteins 114:148 BACKGROUND Arabinogalactan proteins (AGPs) 114:155 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 8 25 theme chains 1256:1261 arg1 accumulation 1233:1244 The extensive accumulation 1219:1244 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall 1219:1350 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 3 26 theme molecular 487:495 arg1 tools 497:501 molecular tools 487:501 molecular tools based on specific monoclonal antibodies recognizing carbohydrate AGP epitopes 487:579 The features of AGPs isolated from fruit were investigated with molecular tools based on specific monoclonal antibodies recognizing carbohydrate AGP epitopes. 36539686 7 27 theme component 1170:1178 arg1 action 1141:1146 The action 1137:1146 The action of a single cell wall component 1137:1178 CONCLUSIONS The action of a single cell wall component does not elicit any influence ex situ. 36539686 0 28 dep composition 73:83 arg1 Working 0:6 Working 0:6 Working 0:6 Working towards arabinogalactan proteins (AGPs) from fruit: carbohydrate composition and impact on fungal growth. 36539686 8 29 theme fungal 1467:1472 arg1 attack 1474:1479 fungal attack 1467:1479 fungal attack 1467:1479 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 1 30 theme matrix 175:180 arg1 constituents 182:193 extracellular matrix constituents 161:193 extracellular matrix constituents involved in plant response to fungal infection 161:240 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 1 30 theme matrix 175:180 arg1 proteins 141:148 BACKGROUND Arabinogalactan proteins 114:148 BACKGROUND Arabinogalactan proteins (AGPs) 114:155 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 5 31 theme AGPs 790:793 arg1 influence 777:785 the influence 773:785 the influence of AGPs on fungal growth 773:810 RESULTS The results definitely ruled out the influence of AGPs on fungal growth. 36539686 4 32 used used 666:669 arg2 Test 656:659 the Agar Invasion Test 638:659 the Agar Invasion Test 638:659 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 36539686 4 32 used used 666:669 arg2 Test 629:632 The Antifungal (well-diffusion) Susceptibility Test 582:632 The Antifungal (well-diffusion) Susceptibility Test 582:632 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 36539686 2 33 theme antifungal 295:304 arg1 effect 306:311 the antifungal effect 291:311 the antifungal effect of AGPs 291:319 The aim of the current study was to investigate the antifungal effect of AGPs ex situ and to determine the structural features of AGPs that may have an influence on this activity. 36539686 8 34 from importance 1367:1376 arg1 response 1455:1462 response 1455:1462 response to fungal attack 1455:1479 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 2 35 theme structural 350:359 arg1 features 361:368 the structural features 346:368 the structural features of AGPs that may have an influence on this activity 346:420 The aim of the current study was to investigate the antifungal effect of AGPs ex situ and to determine the structural features of AGPs that may have an influence on this activity. 36539686 7 36 theme cell 1160:1163 arg1 component 1170:1178 a single cell wall component 1151:1178 a single cell wall component 1151:1178 CONCLUSIONS The action of a single cell wall component does not elicit any influence ex situ. 36539686 4 37 theme Penicillium 703:713 arg1 culture 723:729 Penicillium notatum culture 703:729 Penicillium notatum culture 703:729 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 36539686 8 38 theme glycan 1249:1254 arg1 chains 1256:1261 glycan chains 1249:1261 glycan chains of AGPs in infected tissue 1249:1288 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 3 39 theme monoclonal 521:530 arg1 antibodies 532:541 specific monoclonal antibodies 512:541 specific monoclonal antibodies recognizing carbohydrate AGP epitopes 512:579 The features of AGPs isolated from fruit were investigated with molecular tools based on specific monoclonal antibodies recognizing carbohydrate AGP epitopes. 36539686 0 40 theme arabinogalactan 16:30 arg1 AGPs 42:45 AGPs 42:45 AGPs 42:45 Working towards arabinogalactan proteins (AGPs) from fruit: carbohydrate composition and impact on fungal growth. 36539686 0 40 theme arabinogalactan 16:30 arg1 proteins 32:39 arabinogalactan proteins 16:39 arabinogalactan proteins (AGPs) from fruit 16:57 Working towards arabinogalactan proteins (AGPs) from fruit: carbohydrate composition and impact on fungal growth. 36539686 0 41 from composition 73:83 arg1 growth 106:111 fungal growth 99:111 fungal growth 99:111 Working towards arabinogalactan proteins (AGPs) from fruit: carbohydrate composition and impact on fungal growth. 36539686 6 42 theme in 1091:1092 arg1 conditions 1113:1122 in vitro experimental conditions 1091:1122 in vitro experimental conditions 1091:1122 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 4 43 theme Susceptibility 614:627 arg1 Test 629:632 The Antifungal (well-diffusion) Susceptibility Test 582:632 The Antifungal (well-diffusion) Susceptibility Test 582:632 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 36539686 5 44 dep RESULTS 732:738 arg1 results 744:750 The results 740:750 RESULTS The results 732:750 RESULTS The results definitely ruled out the influence of AGPs on fungal growth. 36539686 8 45 theme extensive 1223:1231 arg1 accumulation 1233:1244 The extensive accumulation 1219:1244 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall 1219:1350 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 4 46 from impact 685:690 arg1 culture 723:729 Penicillium notatum culture 703:729 Penicillium notatum culture 703:729 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 36539686 1 47 theme plant 207:211 arg1 response 213:220 plant response 207:220 plant response to fungal infection 207:240 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 4 48 theme Invasion 647:654 arg1 Test 656:659 the Agar Invasion Test 638:659 the Agar Invasion Test 638:659 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 36539686 8 49 theme particular 1402:1411 arg1 components 1413:1422 particular components 1402:1422 particular components of the extracellular matrix 1402:1450 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 6 50 theme 1 → 2 984:988 arg1 Rha 991:993 GlcA-β(1 → 3)-GalA-α(1 → 2) Rha 963:993 GlcA-β(1 → 3)-GalA-α(1 → 2) Rha 963:993 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 7 51 dep CONCLUSIONS 1125:1135 arg1 elicit 1189:1194 elicit 1189:1194 does not elicit any influence ex situ 1180:1216 CONCLUSIONS The action of a single cell wall component does not elicit any influence ex situ. 36539686 1 52 theme fungal 225:230 arg1 infection 232:240 fungal infection 225:240 fungal infection 225:240 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 0 53 from fruit 53:57 arg1 AGPs 42:45 AGPs 42:45 AGPs 42:45 Working towards arabinogalactan proteins (AGPs) from fruit: carbohydrate composition and impact on fungal growth. 36539686 0 53 from fruit 53:57 arg1 proteins 32:39 arabinogalactan proteins 16:39 arabinogalactan proteins (AGPs) from fruit 16:57 Working towards arabinogalactan proteins (AGPs) from fruit: carbohydrate composition and impact on fungal growth. 36539686 3 54 theme AGP 568:570 arg1 epitopes 572:579 carbohydrate AGP epitopes 555:579 carbohydrate AGP epitopes 555:579 The features of AGPs isolated from fruit were investigated with molecular tools based on specific monoclonal antibodies recognizing carbohydrate AGP epitopes. 36539686 6 55 theme plant 1077:1081 arg1 cell 1083:1086 the plant cell 1073:1086 the plant cell 1073:1086 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 8 56 theme extracellular 1431:1443 arg1 matrix 1445:1450 the extracellular matrix 1427:1450 the extracellular matrix 1427:1450 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 4 57 theme Antifungal 586:595 arg1 Test 629:632 The Antifungal (well-diffusion) Susceptibility Test 582:632 The Antifungal (well-diffusion) Susceptibility Test 582:632 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 36539686 3 58 theme AGPs 439:442 arg1 features 427:434 The features 423:434 The features of AGPs isolated from fruit 423:462 The features of AGPs isolated from fruit were investigated with molecular tools based on specific monoclonal antibodies recognizing carbohydrate AGP epitopes. 36539686 6 59 theme immunochemical 817:830 arg1 analyses 832:839 The immunochemical analyses 813:839 The immunochemical analyses 813:839 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 8 60 from tissue 1283:1288 arg1 chains 1256:1261 glycan chains 1249:1261 glycan chains of AGPs in infected tissue 1249:1288 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 5 61 from influence 777:785 arg1 growth 805:810 fungal growth 798:810 fungal growth 798:810 RESULTS The results definitely ruled out the influence of AGPs on fungal growth. 36539686 8 62 theme dependencies 1381:1392 arg1 importance 1367:1376 the importance 1363:1376 the importance of dependencies between particular components of the extracellular matrix in response to fungal attack 1363:1479 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 6 63 theme glucuronosyl 919:930 arg1 residues 932:939 β-linked glucuronosyl residues 910:939 β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions 910:1122 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 1 64 theme BACKGROUND 114:123 arg1 constituents 182:193 extracellular matrix constituents 161:193 extracellular matrix constituents involved in plant response to fungal infection 161:240 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 1 64 theme BACKGROUND 114:123 arg1 AGPs 151:154 AGPs 151:154 AGPs 151:154 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 1 64 theme BACKGROUND 114:123 arg1 proteins 141:148 BACKGROUND Arabinogalactan proteins 114:148 BACKGROUND Arabinogalactan proteins (AGPs) 114:155 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 8 65 theme mechanism 1315:1323 arg1 result 1295:1300 a result 1293:1300 a result of a complex mechanism occurring in the cell wall 1293:1350 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 2 66 contain have 387:390 arg2 influence 395:403 an influence 392:403 an influence on this activity 392:420 The aim of the current study was to investigate the antifungal effect of AGPs ex situ and to determine the structural features of AGPs that may have an influence on this activity. 36539686 2 66 contain have 387:390 arg1 features 361:368 the structural features 346:368 the structural features of AGPs that may have an influence on this activity 346:420 The aim of the current study was to investigate the antifungal effect of AGPs ex situ and to determine the structural features of AGPs that may have an influence on this activity. 36539686 8 67 theme matrix 1445:1450 arg1 components 1413:1422 particular components 1402:1422 particular components of the extracellular matrix 1402:1450 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 1 68 theme Arabinogalactan 125:139 arg1 constituents 182:193 extracellular matrix constituents 161:193 extracellular matrix constituents involved in plant response to fungal infection 161:240 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 1 68 theme Arabinogalactan 125:139 arg1 AGPs 151:154 AGPs 151:154 AGPs 151:154 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 1 68 theme Arabinogalactan 125:139 arg1 proteins 141:148 BACKGROUND Arabinogalactan proteins 114:148 BACKGROUND Arabinogalactan proteins (AGPs) 114:155 BACKGROUND Arabinogalactan proteins (AGPs) are extracellular matrix constituents involved in plant response to fungal infection. 36539686 8 69 theme infected 1274:1281 arg1 tissue 1283:1288 infected tissue 1274:1288 infected tissue 1274:1288 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 2 70 theme AGPs 316:319 arg1 effect 306:311 the antifungal effect 291:311 the antifungal effect of AGPs 291:319 The aim of the current study was to investigate the antifungal effect of AGPs ex situ and to determine the structural features of AGPs that may have an influence on this activity. 36539686 8 71 from AGPs 1266:1269 arg1 tissue 1283:1288 infected tissue 1274:1288 infected tissue 1274:1288 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 8 72 theme AGPs 1266:1269 arg1 chains 1256:1261 glycan chains 1249:1261 glycan chains of AGPs in infected tissue 1249:1288 The extensive accumulation of glycan chains of AGPs in infected tissue as a result of a complex mechanism occurring in the cell wall emphasizes the importance of dependencies between particular components of the extracellular matrix in response to fungal attack. 36539686 4 73 theme Agar 642:645 arg1 Test 656:659 the Agar Invasion Test 638:659 the Agar Invasion Test 638:659 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 36539686 6 74 theme experimental 1100:1111 arg1 conditions 1113:1122 in vitro experimental conditions 1091:1122 in vitro experimental conditions 1091:1122 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 6 75 theme β-linked 910:917 arg1 residues 932:939 β-linked glucuronosyl residues 910:939 β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions 910:1122 The immunochemical analyses revealed that AGPs consist mainly of carbohydrate chains composed of β-linked glucuronosyl residues recognized by LM2 and GlcA-β(1 → 3)-GalA-α(1 → 2) Rha recognized by JIM13, which do not have the same functional properties outside the plant cell in in vitro experimental conditions. 36539686 5 76 theme fungal 798:803 arg1 growth 805:810 fungal growth 798:810 fungal growth 798:810 RESULTS The results definitely ruled out the influence of AGPs on fungal growth. 36539686 3 77 attach isolated 444:451 arg2 AGPs 439:442 AGPs 439:442 AGPs isolated from fruit 439:462 The features of AGPs isolated from fruit were investigated with molecular tools based on specific monoclonal antibodies recognizing carbohydrate AGP epitopes. 36539686 3 77 attach isolated 444:451 arg1 fruit 458:462 fruit 458:462 fruit 458:462 The features of AGPs isolated from fruit were investigated with molecular tools based on specific monoclonal antibodies recognizing carbohydrate AGP epitopes. 36539686 3 78 theme carbohydrate 555:566 arg1 epitopes 572:579 carbohydrate AGP epitopes 555:579 carbohydrate AGP epitopes 555:579 The features of AGPs isolated from fruit were investigated with molecular tools based on specific monoclonal antibodies recognizing carbohydrate AGP epitopes. 36539686 4 79 theme well-diffusion 598:611 arg1 Test 629:632 The Antifungal (well-diffusion) Susceptibility Test 582:632 The Antifungal (well-diffusion) Susceptibility Test 582:632 The Antifungal (well-diffusion) Susceptibility Test and the Agar Invasion Test were used to assess the impact of AGPs on Penicillium notatum culture. 35464979 8 0 theme metabolism 1264:1273 arg1 downregulation 1222:1235 downregulation 1222:1235 downregulation of glycan biosynthesis and metabolism 1222:1273 Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. 35464979 10 1 theme patients 1727:1734 arg1 impairment 1700:1709 cognitive impairment 1690:1709 cognitive impairment of hypertension patients 1690:1734 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 11 2 theme dysbiosis 1819:1827 arg1 involvement 1782:1792 the involvement 1778:1792 the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients 1778:1871 The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder. 35464979 2 3 theme flora 376:380 arg1 role 336:339 the role 332:339 the role 332:339 Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. 35464979 2 3 theme flora 376:380 arg1 value 356:360 prediction value 345:360 prediction value of intestinal flora 345:380 Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. 35464979 8 4 theme hypertension 1278:1289 arg1 patients 1291:1298 hypertension patients 1278:1298 hypertension patients with cognitive impairment 1278:1324 Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. 35464979 6 5 theme intestinal 846:855 arg1 structure 863:871 intestinal flora structure 846:871 intestinal flora structure 846:871 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 10 6 theme prediction 1608:1617 arg1 9× 1626:1627 9× 1626:1627 9× 1626:1627 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 10 6 theme prediction 1608:1617 arg1 model 1619:1623 the taxa-based multiple joint prediction model 1578:1623 the taxa-based multiple joint prediction model (9×) 1578:1628 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 1 7 theme intestinal 191:200 arg1 flora 202:206 intestinal flora 191:206 intestinal flora 191:206 Growing evidence has demonstrated that hypertension was associated with dysbiosis of intestinal flora. 35464979 10 8 theme multiple 1593:1600 arg1 9× 1626:1627 9× 1626:1627 9× 1626:1627 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 10 8 theme multiple 1593:1600 arg1 model 1619:1623 the taxa-based multiple joint prediction model 1578:1623 the taxa-based multiple joint prediction model (9×) 1578:1628 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 5 9 theme cognitive 745:753 arg1 impairment 755:764 cognitive impairment 745:764 cognitive impairment 745:764 The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). 35464979 10 10 contain have 1650:1653 arg1 9× 1626:1627 9× 1626:1627 9× 1626:1627 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 10 10 contain have 1650:1653 arg1 model 1619:1623 the taxa-based multiple joint prediction model 1578:1623 the taxa-based multiple joint prediction model (9×) 1578:1628 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 10 10 contain have 1650:1653 arg2 potential 1676:1684 excellent diagnostic potential 1655:1684 excellent diagnostic potential for cognitive impairment of hypertension patients 1655:1734 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 9 11 theme LPS-containing 1406:1419 arg1 taxa 1421:1424 LPS-containing taxa 1406:1424 LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) 1406:1526 Additionally, the pathway was demonstrated to be significantly correlated with LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon Prevotella. 35464979 5 12 dep have 740:743 arg1 < 772:772 < 772:772 < 772:772 The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). 35464979 4 13 theme intestinal 546:555 arg1 flora 557:561 intestinal flora 546:561 intestinal flora 546:561 The structure of intestinal flora was analyzed by V3-V4 16S rRNA amplicon sequencing. 35464979 7 14 dep taxa 988:991 arg1 Proteobacteria 994:1007 Proteobacteria 994:1007 Proteobacteria 994:1007 In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. 35464979 0 15 theme Patients-A 81:90 arg1 Study 99:103 Hypertension Patients-A Cohort Study 68:103 Hypertension Patients-A Cohort Study 68:103 Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients-A Cohort Study. 35464979 7 16 dep Proteobacteria 994:1007 arg1 Enterobacteriaceae 1049:1066 Enterobacteriaceae 1049:1066 Enterobacteriaceae 1049:1066 In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. 35464979 7 16 dep Proteobacteria 994:1007 arg1 Escherichia-Shigella 1073:1092 Escherichia-Shigella 1073:1092 Escherichia-Shigella 1073:1092 In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. 35464979 7 16 dep Proteobacteria 994:1007 arg1 Enterobacterales 1031:1046 Enterobacterales 1031:1046 Enterobacterales 1031:1046 In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. 35464979 5 17 theme Montreal 661:668 arg1 scale 698:702 the Montreal Cognitive Assessment (MoCA) scale 657:702 the Montreal Cognitive Assessment (MoCA) scale 657:702 The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). 35464979 3 18 theme hypertension 482:493 arg1 patients 495:502 63 hypertension patients 479:502 63 hypertension patients 479:502 A cohort of 97 participants included 63 hypertension patients and 34 healthy controls. 35464979 5 19 theme cognitive 619:627 arg1 function 629:636 The cognitive function 615:636 The cognitive function 615:636 The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). 35464979 5 20 contain have 740:743 arg1 patients 712:719 31 patients 709:719 31 patients 709:719 The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). 35464979 5 20 contain have 740:743 arg2 impairment 755:764 cognitive impairment 745:764 cognitive impairment 745:764 The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). 35464979 8 21 with patients 1291:1298 arg1 impairment 1315:1324 cognitive impairment 1305:1324 cognitive impairment 1305:1324 Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. 35464979 0 22 theme Gut 0:2 arg1 Signatures 15:24 Gut Microbiome Signatures 0:24 Gut Microbiome Signatures 0:24 Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients-A Cohort Study. 35464979 7 23 theme LPS-containing 973:986 arg1 taxa 988:991 LPS-containing taxa 973:991 LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) 973:1093 In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. 35464979 4 24 theme amplicon 594:601 arg1 sequencing 603:612 V3-V4 16S rRNA amplicon sequencing 579:612 V3-V4 16S rRNA amplicon sequencing 579:612 The structure of intestinal flora was analyzed by V3-V4 16S rRNA amplicon sequencing. 35464979 3 25 theme healthy 511:517 arg1 controls 519:526 34 healthy controls 508:526 34 healthy controls 508:526 A cohort of 97 participants included 63 hypertension patients and 34 healthy controls. 35464979 6 26 theme normal-cognitive 914:929 arg1 patients 931:938 normal-cognitive patients 914:938 normal-cognitive patients 914:938 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 9 27 dep Proteobacteria 1427:1440 arg1 Escherichia-Shigella 1506:1525 Escherichia-Shigella 1506:1525 Escherichia-Shigella 1506:1525 Additionally, the pathway was demonstrated to be significantly correlated with LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon Prevotella. 35464979 9 27 dep Proteobacteria 1427:1440 arg1 Enterobacterales 1464:1479 Enterobacterales 1464:1479 Enterobacterales 1464:1479 Additionally, the pathway was demonstrated to be significantly correlated with LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon Prevotella. 35464979 9 27 dep Proteobacteria 1427:1440 arg1 Enterobacteriaceae 1482:1499 Enterobacteriaceae 1482:1499 Enterobacteriaceae 1482:1499 Additionally, the pathway was demonstrated to be significantly correlated with LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon Prevotella. 35464979 10 28 theme diagnostic 1665:1674 arg1 potential 1676:1684 excellent diagnostic potential 1655:1684 excellent diagnostic potential for cognitive impairment of hypertension patients 1655:1734 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 8 29 theme Tax4Fun 1187:1193 arg1 results 1207:1213 Tax4Fun predication results 1187:1213 Tax4Fun predication results 1187:1213 Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. 35464979 10 30 theme hypertension 1714:1725 arg1 patients 1727:1734 hypertension patients 1714:1734 hypertension patients 1714:1734 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 11 31 theme predictive 1899:1908 arg1 index 1910:1914 an objective predictive index 1886:1914 an objective predictive index for this cognition disorder 1886:1942 The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder. 35464979 2 32 theme intestinal 365:374 arg1 flora 376:380 intestinal flora 365:380 intestinal flora 365:380 Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. 35464979 0 33 theme Cognitive 44:52 arg1 Impairment 54:63 Cognitive Impairment 44:63 Cognitive Impairment in Hypertension Patients-A Cohort Study 44:103 Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients-A Cohort Study. 35464979 9 34 theme taxon 1547:1551 arg1 Prevotella 1553:1562 SCFA-producing taxon Prevotella 1532:1562 SCFA-producing taxon Prevotella 1532:1562 Additionally, the pathway was demonstrated to be significantly correlated with LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon Prevotella. 35464979 4 35 theme 16S 585:587 arg1 sequencing 603:612 V3-V4 16S rRNA amplicon sequencing 579:612 V3-V4 16S rRNA amplicon sequencing 579:612 The structure of intestinal flora was analyzed by V3-V4 16S rRNA amplicon sequencing. 35464979 6 36 with Patients 779:786 arg1 impairment 803:812 cognitive impairment 793:812 cognitive impairment 793:812 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 11 37 theme cognition 1925:1933 arg1 disorder 1935:1942 this cognition disorder 1920:1942 this cognition disorder 1920:1942 The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder. 35464979 11 38 theme microbiota 1808:1817 arg1 dysbiosis 1819:1827 intestinal microbiota dysbiosis 1797:1827 intestinal microbiota dysbiosis 1797:1827 The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder. 35464979 2 39 theme hypertension-associated 396:418 arg1 impairment 430:439 hypertension-associated cognitive impairment 396:439 hypertension-associated cognitive impairment 396:439 Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. 35464979 8 40 theme glycan 1240:1245 arg1 biosynthesis 1247:1258 glycan biosynthesis 1240:1258 glycan biosynthesis 1240:1258 Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. 35464979 11 41 theme hypertension 1851:1862 arg1 patients 1864:1871 cognition-impaired hypertension patients 1832:1871 cognition-impaired hypertension patients 1832:1871 The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder. 35464979 9 42 dep taxa 1421:1424 arg1 Proteobacteria 1427:1440 Proteobacteria 1427:1440 Proteobacteria 1427:1440 Additionally, the pathway was demonstrated to be significantly correlated with LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon Prevotella. 35464979 10 43 theme joint 1602:1606 arg1 9× 1626:1627 9× 1626:1627 9× 1626:1627 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 10 43 theme joint 1602:1606 arg1 model 1619:1623 the taxa-based multiple joint prediction model 1578:1623 the taxa-based multiple joint prediction model (9×) 1578:1628 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 6 44 theme flora 857:861 arg1 structure 863:871 intestinal flora structure 846:871 intestinal flora structure 846:871 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 5 45 theme Assessment 680:689 arg1 scale 698:702 the Montreal Cognitive Assessment (MoCA) scale 657:702 the Montreal Cognitive Assessment (MoCA) scale 657:702 The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). 35464979 11 46 from involvement 1782:1792 arg1 patients 1864:1871 cognition-impaired hypertension patients 1832:1871 cognition-impaired hypertension patients 1832:1871 The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder. 35464979 2 47 from alteration 382:391 arg1 impairment 430:439 hypertension-associated cognitive impairment 396:439 hypertension-associated cognitive impairment 396:439 Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. 35464979 5 48 theme MoCA 692:695 arg1 scale 698:702 the Montreal Cognitive Assessment (MoCA) scale 657:702 the Montreal Cognitive Assessment (MoCA) scale 657:702 The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). 35464979 6 49 theme considerable 818:829 arg1 alterations 831:841 considerable alterations 818:841 considerable alterations in intestinal flora structure, composition, and function 818:898 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 1 50 theme flora 202:206 arg1 dysbiosis 178:186 dysbiosis 178:186 dysbiosis of intestinal flora 178:206 Growing evidence has demonstrated that hypertension was associated with dysbiosis of intestinal flora. 35464979 8 51 theme cognitive 1305:1313 arg1 impairment 1315:1324 cognitive impairment 1305:1324 cognitive impairment 1305:1324 Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. 35464979 10 52 theme taxa-based 1582:1591 arg1 9× 1626:1627 9× 1626:1627 9× 1626:1627 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 10 52 theme taxa-based 1582:1591 arg1 model 1619:1623 the taxa-based multiple joint prediction model 1578:1623 the taxa-based multiple joint prediction model (9×) 1578:1628 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 7 53 theme SCFA-producing 1099:1112 arg1 Prevotella 1121:1130 Prevotella 1121:1130 Prevotella 1121:1130 In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. 35464979 7 53 theme SCFA-producing 1099:1112 arg1 taxon 1114:1118 SCFA-producing taxon 1099:1118 SCFA-producing taxon (Prevotella) 1099:1131 In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. 35464979 7 54 theme taxon 1114:1118 arg1 abundance 960:968 the abundance 956:968 the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) 956:1131 In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. 35464979 2 55 dep role 336:339 arg1 alteration 382:391 alteration 382:391 alteration in hypertension-associated cognitive impairment 382:439 Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. 35464979 0 56 theme Hypertension 68:79 arg1 Study 99:103 Hypertension Patients-A Cohort Study 68:103 Hypertension Patients-A Cohort Study 68:103 Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients-A Cohort Study. 35464979 2 57 theme intestinal-brain 283:298 arg1 axis 300:303 the intestinal-brain axis 279:303 the intestinal-brain axis 279:303 Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. 35464979 4 58 theme flora 557:561 arg1 structure 533:541 The structure 529:541 The structure of intestinal flora 529:561 The structure of intestinal flora was analyzed by V3-V4 16S rRNA amplicon sequencing. 35464979 0 59 theme Cohort 92:97 arg1 Study 99:103 Hypertension Patients-A Cohort Study 68:103 Hypertension Patients-A Cohort Study 68:103 Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients-A Cohort Study. 35464979 7 60 theme cognition-impaired 1158:1175 arg1 patients 1177:1184 cognition-impaired patients 1158:1184 cognition-impaired patients 1158:1184 In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. 35464979 6 61 contain had 814:816 arg1 Patients 779:786 Patients 779:786 Patients with cognitive impairment 779:812 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 6 61 contain had 814:816 arg2 alterations 831:841 considerable alterations 818:841 considerable alterations in intestinal flora structure, composition, and function 818:898 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 0 62 from Impairment 54:63 arg1 Study 99:103 Hypertension Patients-A Cohort Study 68:103 Hypertension Patients-A Cohort Study 68:103 Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients-A Cohort Study. 35464979 5 63 theme Cognitive 670:678 arg1 scale 698:702 the Montreal Cognitive Assessment (MoCA) scale 657:702 the Montreal Cognitive Assessment (MoCA) scale 657:702 The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). 35464979 0 64 theme Microbiome 4:13 arg1 Signatures 15:24 Gut Microbiome Signatures 0:24 Gut Microbiome Signatures 0:24 Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients-A Cohort Study. 35464979 2 65 theme cognitive 420:428 arg1 impairment 430:439 hypertension-associated cognitive impairment 396:439 hypertension-associated cognitive impairment 396:439 Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. 35464979 10 66 dep have 1650:1653 arg1 0.944 1743:1747 0.944 1743:1747 0.944 1743:1747 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 7 67 theme taxa 988:991 arg1 abundance 960:968 the abundance 956:968 the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) 956:1131 In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. 35464979 1 68 theme Growing 106:112 arg1 evidence 114:121 Growing evidence 106:121 Growing evidence 106:121 Growing evidence has demonstrated that hypertension was associated with dysbiosis of intestinal flora. 35464979 8 69 theme predication 1195:1205 arg1 results 1207:1213 Tax4Fun predication results 1187:1213 Tax4Fun predication results 1187:1213 Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. 35464979 6 70 from alterations 831:841 arg1 composition 874:884 composition 874:884 composition 874:884 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 6 70 from alterations 831:841 arg1 function 891:898 function 891:898 function 891:898 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 6 70 from alterations 831:841 arg1 structure 863:871 intestinal flora structure 846:871 intestinal flora structure 846:871 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 3 71 theme participants 457:468 arg1 cohort 444:449 A cohort 442:449 A cohort of 97 participants 442:468 A cohort of 97 participants included 63 hypertension patients and 34 healthy controls. 35464979 4 72 theme V3-V4 579:583 arg1 sequencing 603:612 V3-V4 16S rRNA amplicon sequencing 579:612 V3-V4 16S rRNA amplicon sequencing 579:612 The structure of intestinal flora was analyzed by V3-V4 16S rRNA amplicon sequencing. 35464979 10 73 theme excellent 1655:1663 arg1 potential 1676:1684 excellent diagnostic potential 1655:1684 excellent diagnostic potential for cognitive impairment of hypertension patients 1655:1734 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 11 74 theme objective 1889:1897 arg1 index 1910:1914 an objective predictive index 1886:1914 an objective predictive index for this cognition disorder 1886:1942 The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder. 35464979 6 75 theme cognitive 793:801 arg1 impairment 803:812 cognitive impairment 793:812 cognitive impairment 793:812 Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. 35464979 0 76 theme Impairment 54:63 arg1 Predictive 30:39 Predictive 30:39 Predictive 30:39 Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients-A Cohort Study. 35464979 9 77 theme SCFA-producing 1532:1545 arg1 Prevotella 1553:1562 SCFA-producing taxon Prevotella 1532:1562 SCFA-producing taxon Prevotella 1532:1562 Additionally, the pathway was demonstrated to be significantly correlated with LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon Prevotella. 35464979 4 78 theme rRNA 589:592 arg1 sequencing 603:612 V3-V4 16S rRNA amplicon sequencing 579:612 V3-V4 16S rRNA amplicon sequencing 579:612 The structure of intestinal flora was analyzed by V3-V4 16S rRNA amplicon sequencing. 35464979 11 79 theme current 1755:1761 arg1 study 1763:1767 The current study 1751:1767 The current study 1751:1767 The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder. 35464979 10 80 theme cognitive 1690:1698 arg1 impairment 1700:1709 cognitive impairment 1690:1709 cognitive impairment of hypertension patients 1690:1734 Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). 35464979 2 81 theme intestinal 215:224 arg1 microbes 226:233 intestinal microbes 215:233 intestinal microbes 215:233 Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. 35464979 11 82 theme intestinal 1797:1806 arg1 dysbiosis 1819:1827 intestinal microbiota dysbiosis 1797:1827 intestinal microbiota dysbiosis 1797:1827 The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder. 35464979 2 83 theme prediction 345:354 arg1 value 356:360 prediction value 345:360 prediction value of intestinal flora 345:380 Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. 35464979 8 84 theme biosynthesis 1247:1258 arg1 downregulation 1222:1235 downregulation 1222:1235 downregulation of glycan biosynthesis and metabolism 1222:1273 Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. 35464979 11 85 theme cognition-impaired 1832:1849 arg1 patients 1864:1871 cognition-impaired hypertension patients 1832:1871 cognition-impaired hypertension patients 1832:1871 The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder. 36009266 5 0 theme isorhamnetin 1384:1395 arg1 glycosides 1397:1406 isorhamnetin glycosides 1384:1406 isorhamnetin glycosides 1384:1406 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 3 1 theme antioxidant 590:600 arg1 capacity 602:609 antioxidant capacity 590:609 antioxidant capacity 590:609 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 1 theme antioxidant 590:600 arg1 matter 526:531 the dry matter 518:531 the dry matter 518:531 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 7 2 theme shallot 1605:1611 arg1 accessions 1613:1622 The investigated shallot accessions 1588:1622 The investigated shallot accessions 1588:1622 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36009266 5 3 theme phenolic 1339:1346 arg1 compounds 1348:1356 phenolic compounds 1339:1356 phenolic compounds 1339:1356 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 3 4 theme 34 638:639 arg1 accessions 649:658 34 shallot accessions 638:658 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) 638:757 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 5 5 dep have 1124:1127 arg1 making 1223:1228 making 1223:1228 making them more suitable for fresh consumption by a broader range of consumers 1223:1301 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 5 dep have 1124:1127 arg1 time 1321:1324 the same time 1312:1324 the same time 1312:1324 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 5 dep have 1124:1127 arg1 abundant 1327:1334 abundant 1327:1334 abundant 1327:1334 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 4 6 theme inulin-type 940:950 arg1 prebiotic 1001:1009 an excellent prebiotic 988:1009 considered an excellent prebiotic with beneficial effects on human health 977:1049 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 4 6 theme inulin-type 940:950 arg1 polysaccharides 960:974 polysaccharides 960:974 polysaccharides 960:974 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 4 6 theme inulin-type 940:950 arg1 sugars 952:957 inulin-type sugars 940:957 inulin-type sugars 940:957 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 3 7 theme accessions 649:658 arg1 matter 526:531 the dry matter 518:531 the dry matter 518:531 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 7 theme accessions 649:658 arg1 content 562:568 sugar content 556:568 sugar content 556:568 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 7 theme accessions 649:658 arg1 content 581:587 flavonoid content 571:587 flavonoid content 571:587 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 7 theme accessions 649:658 arg1 capacity 602:609 antioxidant capacity 590:609 antioxidant capacity 590:609 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 7 theme accessions 649:658 arg1 composition 623:633 mineral composition 615:633 mineral composition 615:633 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 6 8 theme Aggregatum 1485:1494 arg1 group 1496:1500 the A. cepa Aggregatum group 1473:1500 the A. cepa Aggregatum group 1473:1500 We also observed a greater biodiversity among accessions within the A. cepa Aggregatum group in all the analyzed physico-chemical parameters compared to the other shallot groups. 36009266 3 9 theme dry 522:524 arg1 content 547:553 pyruvic acid content 534:553 pyruvic acid content 534:553 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 9 theme dry 522:524 arg1 content 562:568 sugar content 556:568 sugar content 556:568 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 9 theme dry 522:524 arg1 capacity 602:609 antioxidant capacity 590:609 antioxidant capacity 590:609 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 9 theme dry 522:524 arg1 matter 526:531 the dry matter 518:531 the dry matter 518:531 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 9 theme dry 522:524 arg1 content 581:587 flavonoid content 571:587 flavonoid content 571:587 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 9 theme dry 522:524 arg1 composition 623:633 mineral composition 615:633 mineral composition 615:633 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 6 10 theme A. 1477:1478 arg1 group 1496:1500 the A. cepa Aggregatum group 1473:1500 the A. cepa Aggregatum group 1473:1500 We also observed a greater biodiversity among accessions within the A. cepa Aggregatum group in all the analyzed physico-chemical parameters compared to the other shallot groups. 36009266 3 11 theme shallot 679:685 arg1 species 687:693 three shallot species 673:693 three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) 673:757 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 11 theme shallot 679:685 arg1 Allium 715:720 Allium 715:720 Allium 715:720 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 11 theme shallot 679:685 arg1 Aggregatum 747:756 Aggregatum 747:756 Aggregatum 747:756 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 11 theme shallot 679:685 arg1 Allium 696:701 Allium 696:701 Allium 696:701 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 1 12 from family 225:230 arg1 Shallots 175:182 Shallots 175:182 Shallots 175:182 Shallots are a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group. 36009266 1 12 from family 225:230 arg1 plant 200:204 a perennial plant 188:204 a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group 188:315 Shallots are a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group. 36009266 3 13 theme acid 542:545 arg1 content 547:553 pyruvic acid content 534:553 pyruvic acid content 534:553 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 13 theme acid 542:545 arg1 matter 526:531 the dry matter 518:531 the dry matter 518:531 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 7 14 contain have 1624:1627 arg2 capacity 1663:1670 an excellent in vitro antioxidant capacity 1629:1670 an excellent in vitro antioxidant capacity 1629:1670 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36009266 7 14 contain have 1624:1627 arg1 accessions 1613:1622 The investigated shallot accessions 1588:1622 The investigated shallot accessions 1588:1622 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36009266 7 14 contain have 1624:1627 arg2 properties 1706:1715 excellent nutritional properties 1684:1715 excellent nutritional properties 1684:1715 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36009266 2 15 used used 343:346 arg2 shallot 327:333 The term shallot 318:333 The term shallot 318:333 The term shallot is also used for diploid and triploid viviparous onions, known as Allium × proliferum (Moench) Schrad and Allium × cornutum Clementi ex Vis., respectively. 36009266 5 16 theme dry 1135:1137 arg1 content 1146:1152 lower dry matter content 1129:1152 lower dry matter content 1129:1152 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 1 17 theme cepa 295:298 arg1 group 311:315 the Allium cepa Aggregatum group 284:315 the Allium cepa Aggregatum group 284:315 Shallots are a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group. 36009266 4 18 theme beneficial 1016:1025 arg1 effects 1027:1033 beneficial effects 1016:1033 beneficial effects on human health 1016:1049 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 5 19 theme A. 1099:1100 arg1 group 1118:1122 the A. cepa Aggregatum group 1095:1122 the A. cepa Aggregatum group 1095:1122 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 1 20 theme group 311:315 arg1 name 276:279 the name 272:279 the name of the Allium cepa Aggregatum group 272:315 Shallots are a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group. 36009266 5 21 from abundant 1327:1334 arg1 compounds 1348:1356 phenolic compounds 1339:1356 phenolic compounds 1339:1356 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 21 from abundant 1327:1334 arg1 quercetin 1370:1378 quercetin 1370:1378 quercetin 1370:1378 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 21 from abundant 1327:1334 arg1 glycosides 1397:1406 isorhamnetin glycosides 1384:1406 isorhamnetin glycosides 1384:1406 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 6 22 theme physico-chemical 1522:1537 arg1 parameters 1539:1548 all the analyzed physico-chemical parameters 1505:1548 all the analyzed physico-chemical parameters 1505:1548 We also observed a greater biodiversity among accessions within the A. cepa Aggregatum group in all the analyzed physico-chemical parameters compared to the other shallot groups. 36009266 5 23 theme consumers 1293:1301 arg1 range 1284:1288 a broader range 1274:1288 a broader range of consumers 1274:1301 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 24 theme Aggregatum 1107:1116 arg1 group 1118:1122 the A. cepa Aggregatum group 1095:1122 the A. cepa Aggregatum group 1095:1122 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 4 25 theme high 857:860 arg1 content 873:879 high dry matter content 857:879 high dry matter content (around 25%) 857:892 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 7 26 dep in 1642:1643 arg1 vitro 1645:1649 vitro 1645:1649 vitro 1645:1649 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36009266 2 27 theme diploid 352:358 arg1 onions 384:389 diploid and triploid viviparous onions 352:389 diploid and triploid viviparous onions 352:389 The term shallot is also used for diploid and triploid viviparous onions, known as Allium × proliferum (Moench) Schrad and Allium × cornutum Clementi ex Vis., respectively. 36009266 4 28 theme matter 866:871 arg1 content 873:879 high dry matter content 857:879 high dry matter content (around 25%) 857:892 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 1 29 theme common 253:258 arg1 onion 260:264 the common onion 249:264 the common onion 249:264 Shallots are a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group. 36009266 5 30 theme same 1316:1319 arg1 time 1321:1324 the same time 1312:1324 the same time 1312:1324 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 31 from compounds 1348:1356 arg1 abundant 1327:1334 abundant 1327:1334 abundant 1327:1334 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 2 32 theme triploid 364:371 arg1 onions 384:389 diploid and triploid viviparous onions 352:389 diploid and triploid viviparous onions 352:389 The term shallot is also used for diploid and triploid viviparous onions, known as Allium × proliferum (Moench) Schrad and Allium × cornutum Clementi ex Vis., respectively. 36009266 2 33 dep Clementi 459:466 arg1 Vis. 471:474 Allium × cornutum Clementi ex Vis., respectively 441:488 Vis. 471:474 The term shallot is also used for diploid and triploid viviparous onions, known as Allium × proliferum (Moench) Schrad and Allium × cornutum Clementi ex Vis., respectively. 36009266 7 34 theme antioxidant 1651:1661 arg1 capacity 1663:1670 an excellent in vitro antioxidant capacity 1629:1670 an excellent in vitro antioxidant capacity 1629:1670 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36009266 6 35 theme shallot 1572:1578 arg1 groups 1580:1585 the other shallot groups 1562:1585 the other shallot groups 1562:1585 We also observed a greater biodiversity among accessions within the A. cepa Aggregatum group in all the analyzed physico-chemical parameters compared to the other shallot groups. 36009266 5 36 theme pyruvic 1200:1206 arg1 content 1213:1219 pyruvic acid content 1200:1219 pyruvic acid content 1200:1219 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 0 37 theme Shallot 49:55 arg1 Allium 85:90 Allium 85:90 Allium 85:90 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 37 theme Shallot 49:55 arg1 Aggregatum 117:126 Aggregatum 117:126 Aggregatum 117:126 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 37 theme Shallot 49:55 arg1 Allium 66:71 Allium 66:71 Allium 66:71 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 37 theme Shallot 49:55 arg1 Species 57:63 Shallot Species 49:63 Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) 49:127 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 7 38 theme in 1642:1643 arg1 capacity 1663:1670 an excellent in vitro antioxidant capacity 1629:1670 an excellent in vitro antioxidant capacity 1629:1670 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36009266 3 39 theme flavonoid 571:579 arg1 content 581:587 flavonoid content 571:587 flavonoid content 571:587 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 39 theme flavonoid 571:579 arg1 matter 526:531 the dry matter 518:531 the dry matter 518:531 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 1 40 theme Alliaceae 215:223 arg1 family 225:230 the Alliaceae family 211:230 the Alliaceae family 211:230 Shallots are a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group. 36009266 3 41 theme mineral 615:621 arg1 matter 526:531 the dry matter 518:531 the dry matter 518:531 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 41 theme mineral 615:621 arg1 composition 623:633 mineral composition 615:633 mineral composition 615:633 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 2 42 theme term 322:325 arg1 shallot 327:333 The term shallot 318:333 The term shallot 318:333 The term shallot is also used for diploid and triploid viviparous onions, known as Allium × proliferum (Moench) Schrad and Allium × cornutum Clementi ex Vis., respectively. 36009266 5 43 from glycosides 1397:1406 arg1 abundant 1327:1334 abundant 1327:1334 abundant 1327:1334 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 4 44 theme Shallot 760:766 arg1 accessions 768:777 Shallot accessions 760:777 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups 760:834 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 7 45 theme investigated 1592:1603 arg1 accessions 1613:1622 The investigated shallot accessions 1588:1622 The investigated shallot accessions 1588:1622 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36009266 5 46 theme other 1059:1063 arg1 hand 1065:1068 the other hand 1055:1068 the other hand 1055:1068 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 4 47 theme considered 977:986 arg1 prebiotic 1001:1009 an excellent prebiotic 988:1009 considered an excellent prebiotic with beneficial effects on human health 977:1049 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 4 47 theme considered 977:986 arg1 sugars 952:957 inulin-type sugars 940:957 inulin-type sugars 940:957 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 3 48 theme shallot 641:647 arg1 accessions 649:658 34 shallot accessions 638:658 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) 638:757 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 5 49 theme fresh 1253:1257 arg1 consumption 1259:1269 fresh consumption 1253:1269 fresh consumption by a broader range of consumers 1253:1301 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 4 50 with prebiotic 1001:1009 arg1 effects 1027:1033 beneficial effects 1016:1033 beneficial effects on human health 1016:1049 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 4 51 theme excellent 991:999 arg1 prebiotic 1001:1009 an excellent prebiotic 988:1009 considered an excellent prebiotic with beneficial effects on human health 977:1049 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 4 51 theme excellent 991:999 arg1 sugars 952:957 inulin-type sugars 940:957 inulin-type sugars 940:957 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 6 52 from biodiversity 1436:1447 arg1 parameters 1539:1548 all the analyzed physico-chemical parameters 1505:1548 all the analyzed physico-chemical parameters 1505:1548 We also observed a greater biodiversity among accessions within the A. cepa Aggregatum group in all the analyzed physico-chemical parameters compared to the other shallot groups. 36009266 7 53 theme nutritional 1694:1704 arg1 properties 1706:1715 excellent nutritional properties 1684:1715 excellent nutritional properties 1684:1715 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36009266 1 54 theme perennial 190:198 arg1 Shallots 175:182 Shallots 175:182 Shallots 175:182 Shallots are a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group. 36009266 1 54 theme perennial 190:198 arg1 plant 200:204 a perennial plant 188:204 a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group 188:315 Shallots are a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group. 36009266 4 55 theme proliferum 818:827 arg1 groups 829:834 the A.× cornutum and A. × proliferum groups 792:834 the A.× cornutum and A. × proliferum groups 792:834 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 6 56 theme cepa 1480:1483 arg1 group 1496:1500 the A. cepa Aggregatum group 1473:1500 the A. cepa Aggregatum group 1473:1500 We also observed a greater biodiversity among accessions within the A. cepa Aggregatum group in all the analyzed physico-chemical parameters compared to the other shallot groups. 36009266 4 57 theme human 1038:1042 arg1 health 1044:1049 human health 1038:1049 human health 1038:1049 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 3 58 dep Allium 715:720 arg1 proliferum 724:733 Allium × proliferum 715:733 Allium × proliferum 715:733 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 5 59 contain have 1124:1127 arg1 accessions 1071:1080 accessions 1071:1080 accessions belonging to the A. cepa Aggregatum group 1071:1122 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 59 contain have 1124:1127 arg2 result 1164:1169 a result 1162:1169 a result 1162:1169 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 59 contain have 1124:1127 arg2 pungency 1178:1185 lower pungency 1172:1185 lower pungency (measured as pyruvic acid content) 1172:1220 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 59 contain have 1124:1127 arg2 content 1146:1152 lower dry matter content 1129:1152 lower dry matter content 1129:1152 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 3 60 theme pyruvic 534:540 arg1 content 547:553 pyruvic acid content 534:553 pyruvic acid content 534:553 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 60 theme pyruvic 534:540 arg1 matter 526:531 the dry matter 518:531 the dry matter 518:531 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 4 61 theme cornutum 800:807 arg1 groups 829:834 the A.× cornutum and A. × proliferum groups 792:834 the A.× cornutum and A. × proliferum groups 792:834 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 5 62 theme lower 1129:1133 arg1 content 1146:1152 lower dry matter content 1129:1152 lower dry matter content 1129:1152 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 4 63 theme dry 862:864 arg1 content 873:879 high dry matter content 857:879 high dry matter content (around 25%) 857:892 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 1 64 theme Aggregatum 300:309 arg1 group 311:315 the Allium cepa Aggregatum group 284:315 the Allium cepa Aggregatum group 284:315 Shallots are a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group. 36009266 5 65 theme cepa 1102:1105 arg1 group 1118:1122 the A. cepa Aggregatum group 1095:1122 the A. cepa Aggregatum group 1095:1122 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 6 66 theme greater 1428:1434 arg1 biodiversity 1436:1447 a greater biodiversity 1426:1447 a greater biodiversity among accessions within the A. cepa Aggregatum group in all the analyzed physico-chemical parameters 1426:1548 We also observed a greater biodiversity among accessions within the A. cepa Aggregatum group in all the analyzed physico-chemical parameters compared to the other shallot groups. 36009266 6 67 theme analyzed 1513:1520 arg1 parameters 1539:1548 all the analyzed physico-chemical parameters 1505:1548 all the analyzed physico-chemical parameters 1505:1548 We also observed a greater biodiversity among accessions within the A. cepa Aggregatum group in all the analyzed physico-chemical parameters compared to the other shallot groups. 36009266 3 68 dep species 687:693 arg1 species 687:693 three shallot species 673:693 three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) 673:757 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 68 dep species 687:693 arg1 Allium 715:720 Allium 715:720 Allium 715:720 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 68 dep species 687:693 arg1 Aggregatum 747:756 Aggregatum 747:756 Aggregatum 747:756 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 68 dep species 687:693 arg1 Allium 696:701 Allium 696:701 Allium 696:701 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 4 69 dep little 906:911 arg1 % 925:925 less than 50% 913:925 a little less than 50% 904:925 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 0 70 dep Allium 85:90 arg1 proliferum 94:103 Allium × proliferum 85:103 Allium × proliferum 85:103 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 71 theme Phytochemical 4:16 arg1 Dependent 164:172 Dependent 164:172 Dependent 164:172 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 71 theme Phytochemical 4:16 arg1 Composition 34:44 The Phytochemical and Nutritional Composition 0:44 Composition 34:44 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 3 72 dep Allium 696:701 arg1 cornutum 705:712 Allium × cornutum 696:712 Allium × cornutum 696:712 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 2 73 dep Allium 401:406 arg1 proliferum 410:419 Allium × proliferum 401:419 Allium × proliferum (Moench) Schrad 401:435 The term shallot is also used for diploid and triploid viviparous onions, known as Allium × proliferum (Moench) Schrad and Allium × cornutum Clementi ex Vis., respectively. 36009266 5 74 theme broader 1276:1282 arg1 range 1284:1288 a broader range 1274:1288 a broader range of consumers 1274:1301 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 75 theme matter 1139:1144 arg1 content 1146:1152 lower dry matter content 1129:1152 lower dry matter content 1129:1152 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 0 76 theme Nutritional 22:32 arg1 Dependent 164:172 Dependent 164:172 Dependent 164:172 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 76 theme Nutritional 22:32 arg1 Composition 34:44 The Phytochemical and Nutritional Composition 0:44 Composition 34:44 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 77 dep Allium 66:71 arg1 cornutum 75:82 Allium × cornutum 66:82 Allium × cornutum 66:82 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 3 78 theme sugar 556:560 arg1 content 562:568 sugar content 556:568 sugar content 556:568 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 3 78 theme sugar 556:560 arg1 matter 526:531 the dry matter 518:531 the dry matter 518:531 In this study, we compared the dry matter, pyruvic acid content, sugar content, flavonoid content, antioxidant capacity and mineral composition of 34 shallot accessions falling into three shallot species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum). 36009266 2 79 theme viviparous 373:382 arg1 onions 384:389 diploid and triploid viviparous onions 352:389 diploid and triploid viviparous onions 352:389 The term shallot is also used for diploid and triploid viviparous onions, known as Allium × proliferum (Moench) Schrad and Allium × cornutum Clementi ex Vis., respectively. 36009266 7 80 theme excellent 1684:1692 arg1 properties 1706:1715 excellent nutritional properties 1684:1715 excellent nutritional properties 1684:1715 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36009266 0 81 dep Species 57:63 arg1 Allium 85:90 Allium 85:90 Allium 85:90 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 81 dep Species 57:63 arg1 Aggregatum 117:126 Aggregatum 117:126 Aggregatum 117:126 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 81 dep Species 57:63 arg1 Allium 66:71 Allium 66:71 Allium 66:71 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 81 dep Species 57:63 arg1 Species 57:63 Shallot Species 49:63 Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) 49:127 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 5 82 dep pungency 1178:1185 arg1 measured 1188:1195 measured 1188:1195 measured as pyruvic acid content 1188:1219 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 0 83 theme Species 57:63 arg1 Dependent 164:172 Dependent 164:172 Dependent 164:172 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 0 83 theme Species 57:63 arg1 Composition 34:44 The Phytochemical and Nutritional Composition 0:44 Composition 34:44 The Phytochemical and Nutritional Composition of Shallot Species (Allium × cornutum, Allium × proliferum and A. cepa Aggregatum) Is Genetically and Environmentally Dependent. 36009266 6 84 theme other 1566:1570 arg1 groups 1580:1585 the other shallot groups 1562:1585 the other shallot groups 1562:1585 We also observed a greater biodiversity among accessions within the A. cepa Aggregatum group in all the analyzed physico-chemical parameters compared to the other shallot groups. 36009266 5 85 theme acid 1208:1211 arg1 content 1213:1219 pyruvic acid content 1200:1219 pyruvic acid content 1200:1219 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 1 86 theme Allium 288:293 arg1 group 311:315 the Allium cepa Aggregatum group 284:315 the Allium cepa Aggregatum group 284:315 Shallots are a perennial plant from the Alliaceae family, classified with the common onion under the name of the Allium cepa Aggregatum group. 36009266 4 87 from effects 1027:1033 arg1 health 1044:1049 human health 1038:1049 human health 1038:1049 Shallot accessions belonging to the A.× cornutum and A. × proliferum groups are characterized by high dry matter content (around 25%), of which a little less than 50% is formed of inulin-type sugars, polysaccharides, considered an excellent prebiotic with beneficial effects on human health. 36009266 5 88 theme lower 1172:1176 arg1 pungency 1178:1185 lower pungency 1172:1185 lower pungency (measured as pyruvic acid content) 1172:1220 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 5 89 from quercetin 1370:1378 arg1 abundant 1327:1334 abundant 1327:1334 abundant 1327:1334 On the other hand, accessions belonging to the A. cepa Aggregatum group have lower dry matter content and, as a result, lower pungency (measured as pyruvic acid content), making them more suitable for fresh consumption by a broader range of consumers, but, at the same time, abundant in phenolic compounds, especially quercetin and isorhamnetin glycosides. 36009266 7 90 theme excellent 1632:1640 arg1 capacity 1663:1670 an excellent in vitro antioxidant capacity 1629:1670 an excellent in vitro antioxidant capacity 1629:1670 The investigated shallot accessions have an excellent in vitro antioxidant capacity, as well as excellent nutritional properties. 36913444 11 0 theme particular 2016:2025 arg1 monosaccharides 2027:2041 particular monosaccharides 2016:2041 particular monosaccharides 2016:2041 As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. 36913444 3 1 theme healthy 557:563 arg1 cohort 574:579 a healthy US adult cohort 555:579 a healthy US adult cohort 555:579 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 9 2 theme P 1799:1799 arg1 < 1801:1801 P < 0.05 1799:1806 P < 0.05 1799:1806 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 11 3 from possible 2054:2061 arg1 future 2070:2075 future 2070:2075 future 2070:2075 As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. 36913444 1 4 theme microbial 287:295 arg1 structure 297:305 gut microbial structure 283:305 gut microbial structure 283:305 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 9 5 theme low 1595:1597 arg1 intake 1599:1604 low intake 1595:1604 low intake of specific monosaccharides 1595:1632 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 10 6 theme Monosaccharide 1822:1835 arg1 intake 1837:1842 CONCLUSIONS Monosaccharide intake 1810:1842 CONCLUSIONS Monosaccharide intake 1810:1842 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 3 7 from composition 531:541 arg1 cohort 574:579 a healthy US adult cohort 555:579 a healthy US adult cohort 555:579 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 4 8 theme mass 879:882 arg1 index 884:888 body mass index 874:888 body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) 874:967 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 1 9 theme carbohydrates 199:211 arg1 assessment 177:186 BACKGROUND Current assessment 158:186 BACKGROUND Current assessment of dietary carbohydrates 158:211 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 4 10 theme 25-29.99 929:936 arg1 normal 891:896 normal 891:896 normal 891:896 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 10 theme 25-29.99 929:936 arg1 kg/m2 938:942 25-29.99 kg/m2 929:942 25-29.99 kg/m2 929:942 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 0 11 theme Inflammation 123:134 arg1 Characteristics 64:78 Characteristics 64:78 Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults 64:155 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 8 12 dep = 1548:1548 arg1 -0.247 1550:1555 -0.247 1550:1555 -0.247 1550:1555 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 2 13 theme Deeper 321:326 arg1 characterization 328:343 Deeper characterization 321:343 Deeper characterization of food carbohydrate composition 321:376 Deeper characterization of food carbohydrate composition can serve to strengthen the link between diet and gastrointestinal health outcomes. 36913444 11 14 from rich 2008:2011 arg1 monosaccharides 2027:2041 particular monosaccharides 2016:2041 particular monosaccharides 2016:2041 As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. 36913444 0 15 theme Healthy 139:145 arg1 Adults 150:155 Healthy US Adults 139:155 Healthy US Adults 139:155 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 11 16 theme specific 1981:1988 arg1 sources 1995:2001 specific food sources 1981:2001 specific food sources 1981:2001 As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. 36913444 10 17 theme gut 1878:1880 arg1 diversity 1892:1900 gut microbial diversity 1878:1900 gut microbial diversity 1878:1900 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 5 18 theme self-administered 1033:1049 arg1 system 1071:1076 the automated self-administered 24-h dietary recall system 1019:1076 the automated self-administered 24-h dietary recall system 1019:1076 Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. 36913444 8 19 dep neopterin 1525:1533 arg1 = 1560:1560 = 1560:1560 = 1560:1560 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 9 20 theme Wald 1673:1676 arg1 taxa 1667:1670 differentially abundant taxa 1643:1670 differentially abundant taxa (Wald test, P < 0.05) 1643:1692 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 9 20 theme Wald 1673:1676 arg1 test 1678:1681 Wald test 1673:1681 Wald test 1673:1681 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 8 21 theme = 1462:1462 arg1 r 1460:1460 Pearson's r 1450:1460 Pearson's r = 0.520 1450:1468 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 6 22 theme monosaccharide 1217:1230 arg1 intake 1232:1237 monosaccharide intake 1217:1237 monosaccharide intake 1217:1237 Dietary recalls were mapped to the Davis Food Glycopedia to estimate monosaccharide intake. 36913444 5 23 theme dietary 1056:1062 arg1 system 1071:1076 the automated self-administered 24-h dietary recall system 1019:1076 the automated self-administered 24-h dietary recall system 1019:1076 Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. 36913444 11 24 theme gut 2110:2112 arg1 microbiota 2114:2123 the gut microbiota 2106:2123 the gut microbiota 2106:2123 As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. 36913444 7 25 with Participants 1240:1251 arg1 % 1261:1261 >75% 1258:1261 >75% of carbohydrate intake mappable to the glycopedia 1258:1311 Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). 36913444 7 25 with Participants 1240:1251 arg1 intake 1279:1284 carbohydrate intake 1266:1284 carbohydrate intake mappable to the glycopedia 1266:1311 Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). 36913444 10 26 theme microbial 1903:1911 arg1 metabolism 1913:1922 microbial metabolism 1903:1922 microbial metabolism 1903:1922 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 5 27 theme shotgun 1117:1123 arg1 sequencing 1136:1145 shotgun metagenome sequencing 1117:1145 shotgun metagenome sequencing 1117:1145 Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. 36913444 3 28 theme diet 662:665 arg1 quality 667:673 diet quality 662:673 diet quality 662:673 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 1 29 theme Current 169:175 arg1 assessment 177:186 BACKGROUND Current assessment 158:186 BACKGROUND Current assessment of dietary carbohydrates 158:211 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 10 30 theme gastrointestinal 1929:1944 arg1 inflammation 1946:1957 gastrointestinal inflammation 1929:1957 gastrointestinal inflammation 1929:1957 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 0 31 theme Gut 87:89 arg1 Microbiota 91:100 the Gut Microbiota and Gastrointestinal Inflammation 83:134 Microbiota 91:100 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 8 32 dep = 1560:1560 arg1 r 1546:1546 Pearson's r 1536:1546 Pearson's r = -0.247 1536:1555 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 4 33 dep METHODS 750:756 arg1 enrolled 800:807 enrolled 800:807 enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories 800:978 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 34 theme 18-33 839:843 arg1 y 845:845 18-33 y 839:845 18-33 y 839:845 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 2 35 theme gastrointestinal 428:443 arg1 outcomes 452:459 gastrointestinal health outcomes 428:459 gastrointestinal health outcomes 428:459 Deeper characterization of food carbohydrate composition can serve to strengthen the link between diet and gastrointestinal health outcomes. 36913444 8 36 dep = 1473:1473 arg1 r 1460:1460 Pearson's r 1450:1460 Pearson's r = 0.520 1450:1468 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 8 37 theme intake 1374:1379 arg1 Diversity 1346:1354 Diversity 1346:1354 Diversity of monosaccharide intake 1346:1379 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 0 38 theme Dietary 0:6 arg1 Intake 8:13 Dietary Intake 0:13 Dietary Intake of Monosaccharides from Foods 0:43 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 7 39 theme = 1330:1330 arg1 N 1328:1328 N = 180 1328:1334 N = 180 1328:1334 Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). 36913444 11 40 dep fine-tune 2096:2104 arg1 microbiota 2114:2123 the gut microbiota 2106:2123 the gut microbiota 2106:2123 As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. 36913444 3 41 theme gut 699:701 arg1 microbiota 703:712 the gut microbiota 695:712 the gut microbiota 695:712 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 10 42 from metabolism 1913:1922 arg1 adults 1970:1975 healthy adults 1962:1975 healthy adults 1962:1975 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 8 43 theme total 1416:1420 arg1 score 1443:1447 the total Healthy Eating Index score 1412:1447 the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) 1412:1486 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 3 44 theme diets 546:550 arg1 composition 531:541 the monosaccharide composition 512:541 the monosaccharide composition of diets in a healthy US adult cohort 512:579 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 4 45 dep index 884:888 arg1 kg/m2 938:942 25-29.99 kg/m2 929:942 25-29.99 kg/m2 929:942 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 45 dep index 884:888 arg1 kg/m2 962:966 30-44 kg/m2 956:966 30-44 kg/m2 956:966 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 45 dep index 884:888 arg1 kg/m2 910:914 18.5-24.99 kg/m2 899:914 18.5-24.99 kg/m2 899:914 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 45 dep index 884:888 arg1 overweight 917:926 overweight 917:926 overweight 917:926 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 45 dep index 884:888 arg1 obese 949:953 obese 949:953 obese 949:953 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 45 dep index 884:888 arg1 normal 891:896 normal 891:896 normal 891:896 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 5 46 theme automated 1023:1031 arg1 system 1071:1076 the automated self-administered 24-h dietary recall system 1019:1076 the automated self-administered 24-h dietary recall system 1019:1076 Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. 36913444 3 47 theme gastrointestinal 719:734 arg1 inflammation 736:747 gastrointestinal inflammation 719:747 gastrointestinal inflammation 719:747 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 8 48 theme Eating 1430:1435 arg1 score 1443:1447 the total Healthy Eating Index score 1412:1447 the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) 1412:1486 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 2 49 theme composition 366:376 arg1 characterization 328:343 Deeper characterization 321:343 Deeper characterization of food carbohydrate composition 321:376 Deeper characterization of food carbohydrate composition can serve to strengthen the link between diet and gastrointestinal health outcomes. 36913444 10 50 from inflammation 1946:1957 arg1 adults 1970:1975 healthy adults 1962:1975 healthy adults 1962:1975 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 5 51 theme dietary 988:994 arg1 intake 996:1001 Recent dietary intake 981:1001 Recent dietary intake 981:1001 Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. 36913444 7 52 theme mappable 1286:1293 arg1 intake 1279:1284 carbohydrate intake 1266:1284 carbohydrate intake mappable to the glycopedia 1266:1311 Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). 36913444 3 53 theme US 565:566 arg1 cohort 574:579 a healthy US adult cohort 555:579 a healthy US adult cohort 555:579 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 7 54 theme carbohydrate 1266:1277 arg1 intake 1279:1284 carbohydrate intake 1266:1284 carbohydrate intake mappable to the glycopedia 1266:1311 Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). 36913444 9 55 theme rank-sum 1784:1791 arg1 test 1793:1796 Wilcoxon rank-sum test 1775:1796 Wilcoxon rank-sum test 1775:1796 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 0 56 from Inflammation 123:134 arg1 Adults 150:155 Healthy US Adults 139:155 Healthy US Adults 139:155 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 11 57 from future 2070:2075 arg1 possible 2054:2061 possible 2054:2061 possible 2054:2061 As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. 36913444 9 58 dep associated 1705:1714 arg1 test 1793:1796 Wilcoxon rank-sum test 1775:1796 Wilcoxon rank-sum test 1775:1796 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 1 59 theme gut 283:285 arg1 structure 297:305 gut microbial structure 283:305 gut microbial structure 283:305 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 4 60 dep age 834:836 arg1 y 845:845 18-33 y 839:845 18-33 y 839:845 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 60 dep age 834:836 arg1 y 854:854 34-49 y 848:854 34-49 y 848:854 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 60 dep age 834:836 arg1 categories 969:978 categories 969:978 categories 969:978 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 60 dep age 834:836 arg1 y 867:867 50-65 y 861:867 50-65 y 861:867 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 0 61 from Adults 150:155 arg1 Characteristics 64:78 Characteristics 64:78 Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults 64:155 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 10 62 theme CONCLUSIONS 1810:1820 arg1 intake 1837:1842 CONCLUSIONS Monosaccharide intake 1810:1842 CONCLUSIONS Monosaccharide intake 1810:1842 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 2 63 theme food 348:351 arg1 composition 366:376 food carbohydrate composition 348:376 food carbohydrate composition 348:376 Deeper characterization of food carbohydrate composition can serve to strengthen the link between diet and gastrointestinal health outcomes. 36913444 1 64 theme dietary 191:197 arg1 carbohydrates 199:211 dietary carbohydrates 191:211 dietary carbohydrates 191:211 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 4 65 theme body 874:877 arg1 index 884:888 body mass index 874:888 body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) 874:967 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 10 66 theme diet 1864:1867 arg1 quality 1869:1875 diet quality 1864:1875 diet quality 1864:1875 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 6 67 theme Dietary 1148:1154 arg1 recalls 1156:1162 Dietary recalls 1148:1162 Dietary recalls 1148:1162 Dietary recalls were mapped to the Davis Food Glycopedia to estimate monosaccharide intake. 36913444 1 68 from effects 272:278 arg1 function 311:318 function 311:318 function 311:318 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 1 68 from effects 272:278 arg1 structure 297:305 gut microbial structure 283:305 gut microbial structure 283:305 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 9 69 theme specific 1609:1616 arg1 monosaccharides 1618:1632 specific monosaccharides 1609:1632 specific monosaccharides 1609:1632 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 3 70 theme monosaccharide 639:652 arg1 intake 654:659 monosaccharide intake 639:659 monosaccharide intake 639:659 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 8 71 dep RESULTS 1338:1344 arg1 associated 1396:1405 associated 1396:1405 positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) 1385:1486 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 8 71 dep RESULTS 1338:1344 arg1 associated 1503:1512 associated 1503:1512 negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3) 1492:1572 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 9 72 theme abundant 1658:1665 arg1 taxa 1667:1670 differentially abundant taxa 1643:1670 differentially abundant taxa (Wald test, P < 0.05) 1643:1692 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 9 72 theme abundant 1658:1665 arg1 test 1678:1681 Wald test 1673:1681 Wald test 1673:1681 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 0 73 from Characteristics 64:78 arg1 Adults 150:155 Healthy US Adults 139:155 Healthy US Adults 139:155 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 10 74 theme microbial 1882:1890 arg1 diversity 1892:1900 gut microbial diversity 1878:1900 gut microbial diversity 1878:1900 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 1 75 from properties 257:266 arg1 function 311:318 function 311:318 function 311:318 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 1 75 from properties 257:266 arg1 structure 297:305 gut microbial structure 283:305 gut microbial structure 283:305 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 5 76 theme gut 1083:1085 arg1 microbiota 1087:1096 gut microbiota 1083:1096 gut microbiota 1083:1096 Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. 36913444 8 77 dep score 1443:1447 arg1 = 1473:1473 = 1473:1473 = 1473:1473 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 9 78 theme monosaccharides 1618:1632 arg1 intake 1599:1604 low intake 1595:1604 low intake of specific monosaccharides 1595:1632 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 4 79 theme observational 763:775 arg1 study 794:798 This observational, cross-sectional study 758:798 study 794:798 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 11 80 from monosaccharides 2027:2041 arg1 rich 2008:2011 rich 2008:2011 rich 2008:2011 As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. 36913444 5 81 theme 24-h 1051:1054 arg1 system 1071:1076 the automated self-administered 24-h dietary recall system 1019:1076 the automated self-administered 24-h dietary recall system 1019:1076 Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. 36913444 11 82 theme food 1990:1993 arg1 sources 1995:2001 specific food sources 1981:2001 specific food sources 1981:2001 As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. 36913444 0 83 from Microbiota 91:100 arg1 Adults 150:155 Healthy US Adults 139:155 Healthy US Adults 139:155 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 4 84 theme cross-sectional 778:792 arg1 study 794:798 This observational, cross-sectional study 758:798 study 794:798 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 5 85 theme recall 1064:1069 arg1 system 1071:1076 the automated self-administered 24-h dietary recall system 1019:1076 the automated self-administered 24-h dietary recall system 1019:1076 Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. 36913444 9 86 theme P 1684:1684 arg1 < 1686:1686 P < 0.05 1684:1691 P < 0.05 1684:1691 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 9 87 dep test 1678:1681 arg1 < 1686:1686 P < 0.05 1684:1691 P < 0.05 1684:1691 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 5 88 theme metagenome 1125:1134 arg1 sequencing 1136:1145 shotgun metagenome sequencing 1117:1145 shotgun metagenome sequencing 1117:1145 Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. 36913444 1 89 theme BACKGROUND 158:167 arg1 assessment 177:186 BACKGROUND Current assessment 158:186 BACKGROUND Current assessment of dietary carbohydrates 158:211 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 0 90 from Intake 8:13 arg1 Foods 39:43 Foods 39:43 Foods 39:43 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 0 91 theme Microbiota 91:100 arg1 Characteristics 64:78 Characteristics 64:78 Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults 64:155 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 10 92 from quality 1869:1875 arg1 adults 1970:1975 healthy adults 1962:1975 healthy adults 1962:1975 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 0 93 theme Gastrointestinal 106:121 arg1 Inflammation 123:134 the Gut Microbiota and Gastrointestinal Inflammation 83:134 Inflammation 123:134 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 11 94 theme gastrointestinal 2129:2144 arg1 function 2146:2153 gastrointestinal function 2129:2153 gastrointestinal function 2129:2153 As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. 36913444 0 95 from Foods 39:43 arg1 Monosaccharides 18:32 Monosaccharides 18:32 Monosaccharides from Foods 18:43 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 0 95 from Foods 39:43 arg1 Intake 8:13 Dietary Intake 0:13 Dietary Intake of Monosaccharides from Foods 0:43 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 10 96 from diversity 1892:1900 arg1 adults 1970:1975 healthy adults 1962:1975 healthy adults 1962:1975 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 0 97 theme US 147:148 arg1 Adults 150:155 Healthy US Adults 139:155 Healthy US Adults 139:155 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 8 98 theme fecal 1519:1523 arg1 neopterin 1525:1533 fecal neopterin 1519:1533 fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3) 1519:1572 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 3 99 dep OBJECTIVES 462:471 arg1 aims 491:494 aims 491:494 aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation 491:747 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 8 100 theme monosaccharide 1359:1372 arg1 intake 1374:1379 monosaccharide intake 1359:1379 monosaccharide intake 1359:1379 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 3 101 theme present 477:483 arg1 study 485:489 The present study 473:489 The present study 473:489 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 0 102 theme Monosaccharides 18:32 arg1 Intake 8:13 Dietary Intake 0:13 Dietary Intake of Monosaccharides from Foods 0:43 Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults. 36913444 9 103 dep test 1793:1796 arg1 < 1801:1801 P < 0.05 1799:1806 P < 0.05 1799:1806 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 9 104 theme functional 1725:1734 arg1 capacity 1736:1743 the functional capacity 1721:1743 the functional capacity to break down these monomers 1721:1772 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 3 105 theme monosaccharide 516:529 arg1 composition 531:541 the monosaccharide composition 512:541 the monosaccharide composition of diets in a healthy US adult cohort 512:579 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 8 106 dep = 1462:1462 arg1 0.520 1464:1468 0.520 1464:1468 0.520 1464:1468 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 10 107 theme healthy 1962:1968 arg1 adults 1970:1975 healthy adults 1962:1975 healthy adults 1962:1975 CONCLUSIONS Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. 36913444 2 108 theme health 445:450 arg1 outcomes 452:459 gastrointestinal health outcomes 428:459 gastrointestinal health outcomes 428:459 Deeper characterization of food carbohydrate composition can serve to strengthen the link between diet and gastrointestinal health outcomes. 36913444 8 109 theme = 1548:1548 arg1 r 1546:1546 Pearson's r 1536:1546 Pearson's r = -0.247 1536:1555 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 4 110 theme 50-65 861:865 arg1 y 867:867 50-65 y 861:867 50-65 y 861:867 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 4 111 theme 34-49 848:852 arg1 y 854:854 34-49 y 848:854 34-49 y 848:854 METHODS This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. 36913444 5 112 theme Recent 981:986 arg1 intake 996:1001 Recent dietary intake 981:1001 Recent dietary intake 981:1001 Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. 36913444 7 113 theme intake 1279:1284 arg1 % 1261:1261 >75% 1258:1261 >75% of carbohydrate intake mappable to the glycopedia 1258:1311 Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). 36913444 7 113 theme intake 1279:1284 arg1 intake 1279:1284 carbohydrate intake 1266:1284 carbohydrate intake mappable to the glycopedia 1266:1311 Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). 36913444 3 114 theme microbiota 703:712 arg1 inflammation 736:747 gastrointestinal inflammation 719:747 gastrointestinal inflammation 719:747 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 3 114 theme microbiota 703:712 arg1 intake 654:659 monosaccharide intake 639:659 monosaccharide intake 639:659 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 3 114 theme microbiota 703:712 arg1 quality 667:673 diet quality 662:673 diet quality 662:673 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 3 114 theme microbiota 703:712 arg1 characteristics 676:690 characteristics 676:690 characteristics of the gut microbiota 676:712 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 36913444 8 115 theme Healthy 1422:1428 arg1 score 1443:1447 the total Healthy Eating Index score 1412:1447 the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) 1412:1486 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 2 116 theme carbohydrate 353:364 arg1 composition 366:376 food carbohydrate composition 348:376 food carbohydrate composition 348:376 Deeper characterization of food carbohydrate composition can serve to strengthen the link between diet and gastrointestinal health outcomes. 36913444 1 117 theme nutritional 245:255 arg1 properties 257:266 the nutritional properties 241:266 the nutritional properties 241:266 BACKGROUND Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. 36913444 7 118 dep included 1318:1325 arg1 N 1328:1328 N = 180 1328:1334 N = 180 1328:1334 Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). 36913444 9 119 theme Wilcoxon 1775:1782 arg1 test 1793:1796 Wilcoxon rank-sum test 1775:1796 Wilcoxon rank-sum test 1775:1796 Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). 36913444 8 120 theme Index 1437:1441 arg1 score 1443:1447 the total Healthy Eating Index score 1412:1447 the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) 1412:1486 RESULTS Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). 36913444 3 121 theme adult 568:572 arg1 cohort 574:579 a healthy US adult cohort 555:579 a healthy US adult cohort 555:579 OBJECTIVES The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. 35654518 6 0 link CMOF-derived 1269:1280 arg1 DOM 1282:1284 CMOF-derived DOM 1269:1284 CMOF-derived DOM 1269:1284 Regarding CMOF-derived DOM, the fulvic-like substances associated with aromatic (C=C) and carboxylic groups displayed a faster response to Pb ions on day 0. 35654518 1 1 theme incubation 372:381 arg1 experiment 383:392 a one-year field incubation experiment 355:392 a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis 355:521 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 8 2 theme higher 1640:1645 arg1 risk 1647:1650 a higher risk 1638:1650 a higher risk of Pb 1638:1656 It is noteworthy that the polysaccharides, which participated in Pb binding to CMOF-derived DOM, posed a higher risk of Pb in the environment after 360 days. 35654518 1 3 theme binding 215:221 arg1 properties 223:232 the lead (Pb) binding properties 201:232 the lead (Pb) binding properties of dissolved organic matter (DOM) 201:266 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 2 4 theme hydrophobic 562:572 arg1 substances 586:595 high aromatic and hydrophobic fluorescent substances 544:595 high aromatic and hydrophobic fluorescent substances 544:595 Results showed that high aromatic and hydrophobic fluorescent substances were enriched in CMOF-derived DOM and SWOF-derived DOM and enhanced over time. 35654518 3 5 theme fulvic-like 703:713 arg1 substances 715:724 the fulvic-like substances 699:724 the fulvic-like substances for SWOF-derived DOM 699:745 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 2 6 theme CMOF-derived 614:625 arg1 DOM 627:629 CMOF-derived DOM 614:629 CMOF-derived DOM 614:629 Results showed that high aromatic and hydrophobic fluorescent substances were enriched in CMOF-derived DOM and SWOF-derived DOM and enhanced over time. 35654518 9 7 theme soil 1824:1827 arg1 amendment 1811:1819 the amendment 1807:1819 the amendment of soil 1807:1827 Therefore, these findings gave new insights into the long-term applications of commercial organic fertilizers for the amendment of soil. 35654518 1 8 theme excitation-emission 404:422 arg1 EEM-PARAFAC 448:458 EEM-PARAFAC 448:458 EEM-PARAFAC 448:458 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 8 theme excitation-emission 404:422 arg1 factor 440:445 the excitation-emission matrix-parallel factor 400:445 the excitation-emission matrix-parallel factor (EEM-PARAFAC) 400:459 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 8 theme excitation-emission 404:422 arg1 2DCOS 507:511 2DCOS 507:511 2DCOS 507:511 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 9 theme composition 144:154 arg1 characteristics 156:170 composition characteristics 144:170 composition characteristics 144:170 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 10 theme factor 440:445 arg1 analysis 514:521 the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis 400:521 the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis 400:521 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 4 11 theme humic-like 931:940 arg1 substances 942:951 fluorescent humic-like substances 919:951 fluorescent humic-like substances 919:951 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 1 12 attach derived 268:274 arg1 SWOF 296:299 SWOF 296:299 SWOF 296:299 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 12 attach derived 268:274 arg1 seaweed-based 281:293 seaweed-based 281:293 seaweed-based 281:293 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 12 attach derived 268:274 arg2 characteristics 156:170 composition characteristics 144:170 composition characteristics 144:170 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 13 theme subsequent 180:189 arg1 effect 191:196 the subsequent effect 176:196 the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) 176:266 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 4 14 theme lead 1102:1105 arg1 process 1115:1121 the lead binding process 1098:1121 the lead binding process 1098:1121 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 6 15 theme fulvic-like 1291:1301 arg1 substances 1303:1312 the fulvic-like substances 1287:1312 the fulvic-like substances associated with aromatic (C=C) and carboxylic groups 1287:1365 Regarding CMOF-derived DOM, the fulvic-like substances associated with aromatic (C=C) and carboxylic groups displayed a faster response to Pb ions on day 0. 35654518 1 16 from effect 191:196 arg1 properties 223:232 the lead (Pb) binding properties 201:232 the lead (Pb) binding properties of dissolved organic matter (DOM) 201:266 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 4 17 theme non-fluorescent 883:897 arg1 polysaccharides 899:913 non-fluorescent polysaccharides 883:913 non-fluorescent polysaccharides 883:913 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 5 18 theme aromatic 1175:1182 arg1 groups 1203:1208 aromatic (C=C) and phenolic groups 1175:1208 aromatic (C=C) and phenolic groups 1175:1208 In contrast, humic-like substances associated with aromatic (C=C) and phenolic groups gave a faster response to Pb binding on day 360. 35654518 3 19 from groups 689:694 arg1 substances 785:794 the humic-like substances 770:794 the humic-like substances for CMOF-derived DOM 770:815 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 3 19 from groups 689:694 arg1 substances 715:724 the fulvic-like substances 699:724 the fulvic-like substances for SWOF-derived DOM 699:745 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 3 20 theme carboxyl 751:758 arg1 groups 760:765 carboxyl groups 751:765 carboxyl groups in the humic-like substances for CMOF-derived DOM 751:815 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 6 21 theme CMOF-derived 1269:1280 arg1 DOM 1282:1284 CMOF-derived DOM 1269:1284 CMOF-derived DOM 1269:1284 Regarding CMOF-derived DOM, the fulvic-like substances associated with aromatic (C=C) and carboxylic groups displayed a faster response to Pb ions on day 0. 35654518 1 22 theme one-year 357:364 arg1 experiment 383:392 a one-year field incubation experiment 355:392 a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis 355:521 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 23 from characteristics 156:170 arg1 properties 223:232 the lead (Pb) binding properties 201:232 the lead (Pb) binding properties of dissolved organic matter (DOM) 201:266 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 3 24 link SWOF-derived 730:741 arg1 DOM 743:745 SWOF-derived DOM 730:745 SWOF-derived DOM 730:745 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 3 25 theme humic-like 774:783 arg1 substances 785:794 the humic-like substances 770:794 the humic-like substances for CMOF-derived DOM 770:815 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 0 26 theme dissolved 39:47 arg1 matter 57:62 dissolved organic matter 39:62 dissolved organic matter 39:62 Interactions between lead(II) ions and dissolved organic matter derived from organic fertilizers incubated in the field. 35654518 0 27 theme lead 21:24 arg1 ions 30:33 lead(II) ions 21:33 lead(II) ions 21:33 Interactions between lead(II) ions and dissolved organic matter derived from organic fertilizers incubated in the field. 35654518 4 28 from DOM 1070:1072 arg1 day 1077:1079 day 0 and 180 1077:1089 day 1077:1079 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 4 28 from DOM 1070:1072 arg1 180 1087:1089 180 1087:1089 180 1087:1089 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 5 29 theme Pb 1236:1237 arg1 binding 1239:1245 Pb binding 1236:1245 Pb binding 1236:1245 In contrast, humic-like substances associated with aromatic (C=C) and phenolic groups gave a faster response to Pb binding on day 360. 35654518 8 30 link CMOF-derived 1614:1625 arg1 DOM 1627:1629 CMOF-derived DOM 1614:1629 CMOF-derived DOM 1614:1629 It is noteworthy that the polysaccharides, which participated in Pb binding to CMOF-derived DOM, posed a higher risk of Pb in the environment after 360 days. 35654518 5 31 dep aromatic 1175:1182 arg1 C=C 1185:1187 C=C 1185:1187 C=C 1185:1187 In contrast, humic-like substances associated with aromatic (C=C) and phenolic groups gave a faster response to Pb binding on day 360. 35654518 2 32 theme SWOF-derived 635:646 arg1 DOM 648:650 SWOF-derived DOM 635:650 SWOF-derived DOM 635:650 Results showed that high aromatic and hydrophobic fluorescent substances were enriched in CMOF-derived DOM and SWOF-derived DOM and enhanced over time. 35654518 4 33 theme aromatic 984:991 arg1 groups 999:1004 aromatic (C=C) groups 984:1004 aromatic (C=C) groups 984:1004 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 6 34 theme aromatic 1330:1337 arg1 groups 1360:1365 aromatic (C=C) and carboxylic groups 1330:1365 aromatic (C=C) and carboxylic groups 1330:1365 Regarding CMOF-derived DOM, the fulvic-like substances associated with aromatic (C=C) and carboxylic groups displayed a faster response to Pb ions on day 0. 35654518 1 35 theme manure 314:319 arg1 CMOF 342:345 CMOF 342:345 CMOF 342:345 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 35 theme manure 314:319 arg1 fertilizers 329:339 chicken manure organic fertilizers 306:339 chicken manure organic fertilizers (CMOF) 306:346 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 36 theme dissolved 237:245 arg1 matter 255:260 dissolved organic matter 237:260 dissolved organic matter (DOM) 237:266 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 36 theme dissolved 237:245 arg1 DOM 263:265 DOM 263:265 DOM 263:265 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 4 37 theme Pb 1051:1052 arg1 process 1040:1046 the binding process 1028:1046 the binding process of Pb to SWOF-derived DOM on day 0 and 180 1028:1089 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 3 38 link CMOF-derived 800:811 arg1 DOM 813:815 CMOF-derived DOM 800:815 CMOF-derived DOM 800:815 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 6 39 theme Pb 1398:1399 arg1 ions 1401:1404 Pb ions 1398:1404 Pb ions 1398:1404 Regarding CMOF-derived DOM, the fulvic-like substances associated with aromatic (C=C) and carboxylic groups displayed a faster response to Pb ions on day 0. 35654518 1 40 theme matter 255:260 arg1 properties 223:232 the lead (Pb) binding properties 201:232 the lead (Pb) binding properties of dissolved organic matter (DOM) 201:266 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 3 41 contain had 817:819 arg2 responses 833:841 the fastest responses 821:841 the fastest responses 821:841 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 3 41 contain had 817:819 arg1 groups 689:694 phenolic groups 680:694 phenolic groups in the fulvic-like substances for SWOF-derived DOM 680:745 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 3 41 contain had 817:819 arg1 groups 760:765 carboxyl groups 751:765 carboxyl groups in the humic-like substances for CMOF-derived DOM 751:815 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 0 42 theme II 26:27 arg1 ions 30:33 lead(II) ions 21:33 lead(II) ions 21:33 Interactions between lead(II) ions and dissolved organic matter derived from organic fertilizers incubated in the field. 35654518 9 43 theme commercial 1772:1781 arg1 fertilizers 1791:1801 commercial organic fertilizers 1772:1801 commercial organic fertilizers for the amendment of soil 1772:1827 Therefore, these findings gave new insights into the long-term applications of commercial organic fertilizers for the amendment of soil. 35654518 9 44 theme fertilizers 1791:1801 arg1 applications 1756:1767 the long-term applications 1742:1767 the long-term applications of commercial organic fertilizers for the amendment of soil 1742:1827 Therefore, these findings gave new insights into the long-term applications of commercial organic fertilizers for the amendment of soil. 35654518 1 45 theme two-dimensional 465:479 arg1 spectroscopy 493:504 two-dimensional correlation spectroscopy 465:504 two-dimensional correlation spectroscopy 465:504 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 46 theme spectroscopy 493:504 arg1 analysis 514:521 the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis 400:521 the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis 400:521 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 8 47 theme CMOF-derived 1614:1625 arg1 DOM 1627:1629 CMOF-derived DOM 1614:1629 CMOF-derived DOM 1614:1629 It is noteworthy that the polysaccharides, which participated in Pb binding to CMOF-derived DOM, posed a higher risk of Pb in the environment after 360 days. 35654518 5 48 theme faster 1217:1222 arg1 response 1224:1231 a faster response 1215:1231 a faster response to Pb binding 1215:1245 In contrast, humic-like substances associated with aromatic (C=C) and phenolic groups gave a faster response to Pb binding on day 360. 35654518 4 49 with substances 968:977 arg1 groups 999:1004 aromatic (C=C) groups 984:1004 aromatic (C=C) groups 984:1004 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 4 50 theme SWOF-derived 1057:1068 arg1 DOM 1070:1072 SWOF-derived DOM 1057:1072 SWOF-derived DOM on day 0 and 180 1057:1089 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 2 51 theme fluorescent 574:584 arg1 substances 586:595 high aromatic and hydrophobic fluorescent substances 544:595 high aromatic and hydrophobic fluorescent substances 544:595 Results showed that high aromatic and hydrophobic fluorescent substances were enriched in CMOF-derived DOM and SWOF-derived DOM and enhanced over time. 35654518 2 52 link CMOF-derived 614:625 arg1 DOM 627:629 CMOF-derived DOM 614:629 CMOF-derived DOM 614:629 Results showed that high aromatic and hydrophobic fluorescent substances were enriched in CMOF-derived DOM and SWOF-derived DOM and enhanced over time. 35654518 5 53 theme phenolic 1194:1201 arg1 groups 1203:1208 aromatic (C=C) and phenolic groups 1175:1208 aromatic (C=C) and phenolic groups 1175:1208 In contrast, humic-like substances associated with aromatic (C=C) and phenolic groups gave a faster response to Pb binding on day 360. 35654518 1 54 theme matrix-parallel 424:438 arg1 EEM-PARAFAC 448:458 EEM-PARAFAC 448:458 EEM-PARAFAC 448:458 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 54 theme matrix-parallel 424:438 arg1 factor 440:445 the excitation-emission matrix-parallel factor 400:445 the excitation-emission matrix-parallel factor (EEM-PARAFAC) 400:459 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 54 theme matrix-parallel 424:438 arg1 2DCOS 507:511 2DCOS 507:511 2DCOS 507:511 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 8 55 theme Pb 1655:1656 arg1 risk 1647:1650 a higher risk 1638:1650 a higher risk of Pb 1638:1656 It is noteworthy that the polysaccharides, which participated in Pb binding to CMOF-derived DOM, posed a higher risk of Pb in the environment after 360 days. 35654518 7 56 contain had 1492:1494 arg2 response 1505:1512 a faster response 1496:1512 a faster response 1496:1512 Nonetheless, polysaccharides and humic-like associated with phenolic groups had a faster response on days 180 and 360. 35654518 7 56 contain had 1492:1494 arg1 humic-like 1449:1458 humic-like 1449:1458 humic-like 1449:1458 Nonetheless, polysaccharides and humic-like associated with phenolic groups had a faster response on days 180 and 360. 35654518 7 56 contain had 1492:1494 arg1 polysaccharides 1429:1443 polysaccharides 1429:1443 polysaccharides 1429:1443 Nonetheless, polysaccharides and humic-like associated with phenolic groups had a faster response on days 180 and 360. 35654518 6 57 dep aromatic 1330:1337 arg1 C=C 1340:1342 C=C 1340:1342 C=C 1340:1342 Regarding CMOF-derived DOM, the fulvic-like substances associated with aromatic (C=C) and carboxylic groups displayed a faster response to Pb ions on day 0. 35654518 4 58 link SWOF-derived 1057:1068 arg1 DOM 1070:1072 SWOF-derived DOM 1057:1072 SWOF-derived DOM on day 0 and 180 1057:1089 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 4 59 dep aromatic 984:991 arg1 C=C 994:996 C=C 994:996 C=C 994:996 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 4 60 theme fluorescent 919:929 arg1 substances 942:951 fluorescent humic-like substances 919:951 fluorescent humic-like substances 919:951 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 4 61 theme binding 1107:1113 arg1 process 1115:1121 the lead binding process 1098:1121 the lead binding process 1098:1121 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 3 62 theme SWOF-derived 730:741 arg1 DOM 743:745 SWOF-derived DOM 730:745 SWOF-derived DOM 730:745 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 9 63 theme long-term 1746:1754 arg1 applications 1756:1767 the long-term applications 1742:1767 the long-term applications of commercial organic fertilizers for the amendment of soil 1742:1827 Therefore, these findings gave new insights into the long-term applications of commercial organic fertilizers for the amendment of soil. 35654518 2 64 theme high 544:547 arg1 substances 586:595 high aromatic and hydrophobic fluorescent substances 544:595 high aromatic and hydrophobic fluorescent substances 544:595 Results showed that high aromatic and hydrophobic fluorescent substances were enriched in CMOF-derived DOM and SWOF-derived DOM and enhanced over time. 35654518 2 65 theme aromatic 549:556 arg1 substances 586:595 high aromatic and hydrophobic fluorescent substances 544:595 high aromatic and hydrophobic fluorescent substances 544:595 Results showed that high aromatic and hydrophobic fluorescent substances were enriched in CMOF-derived DOM and SWOF-derived DOM and enhanced over time. 35654518 3 66 theme CMOF-derived 800:811 arg1 DOM 813:815 CMOF-derived DOM 800:815 CMOF-derived DOM 800:815 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 0 67 theme organic 49:55 arg1 matter 57:62 dissolved organic matter 39:62 dissolved organic matter 39:62 Interactions between lead(II) ions and dissolved organic matter derived from organic fertilizers incubated in the field. 35654518 1 68 theme field 366:370 arg1 experiment 383:392 a one-year field incubation experiment 355:392 a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis 355:521 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 6 69 theme carboxylic 1349:1358 arg1 groups 1360:1365 aromatic (C=C) and carboxylic groups 1330:1365 aromatic (C=C) and carboxylic groups 1330:1365 Regarding CMOF-derived DOM, the fulvic-like substances associated with aromatic (C=C) and carboxylic groups displayed a faster response to Pb ions on day 0. 35654518 3 70 from groups 760:765 arg1 substances 785:794 the humic-like substances 770:794 the humic-like substances for CMOF-derived DOM 770:815 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 3 70 from groups 760:765 arg1 substances 715:724 the fulvic-like substances 699:724 the fulvic-like substances for SWOF-derived DOM 699:745 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 3 71 theme fastest 825:831 arg1 responses 833:841 the fastest responses 821:841 the fastest responses 821:841 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35654518 0 72 theme organic 77:83 arg1 fertilizers 85:95 organic fertilizers 77:95 organic fertilizers incubated in the field 77:118 Interactions between lead(II) ions and dissolved organic matter derived from organic fertilizers incubated in the field. 35654518 4 73 theme fulvic-like 956:966 arg1 substances 968:977 fulvic-like substances 956:977 fulvic-like substances 956:977 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 1 74 from fertilizers 329:339 arg1 properties 223:232 the lead (Pb) binding properties 201:232 the lead (Pb) binding properties of dissolved organic matter (DOM) 201:266 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 75 theme chicken 306:312 arg1 CMOF 342:345 CMOF 342:345 CMOF 342:345 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 75 theme chicken 306:312 arg1 fertilizers 329:339 chicken manure organic fertilizers 306:339 chicken manure organic fertilizers (CMOF) 306:346 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 4 76 with substances 942:951 arg1 groups 999:1004 aromatic (C=C) groups 984:1004 aromatic (C=C) groups 984:1004 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 9 77 theme new 1724:1726 arg1 insights 1728:1735 new insights 1724:1735 new insights into the long-term applications of commercial organic fertilizers for the amendment of soil 1724:1827 Therefore, these findings gave new insights into the long-term applications of commercial organic fertilizers for the amendment of soil. 35654518 1 78 theme organic 321:327 arg1 CMOF 342:345 CMOF 342:345 CMOF 342:345 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 78 theme organic 321:327 arg1 fertilizers 329:339 chicken manure organic fertilizers 306:339 chicken manure organic fertilizers (CMOF) 306:346 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 4 79 theme binding 1032:1038 arg1 process 1040:1046 the binding process 1028:1046 the binding process of Pb to SWOF-derived DOM on day 0 and 180 1028:1089 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 1 80 theme organic 247:253 arg1 matter 255:260 dissolved organic matter 237:260 dissolved organic matter (DOM) 237:266 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 80 theme organic 247:253 arg1 DOM 263:265 DOM 263:265 DOM 263:265 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 4 81 with polysaccharides 899:913 arg1 groups 999:1004 aromatic (C=C) groups 984:1004 aromatic (C=C) groups 984:1004 Moreover, both non-fluorescent polysaccharides and fluorescent humic-like substances or fulvic-like substances with aromatic (C=C) groups first participated in the binding process of Pb to SWOF-derived DOM on day 0 and 180 during the lead binding process. 35654518 2 82 link SWOF-derived 635:646 arg1 DOM 648:650 SWOF-derived DOM 635:650 SWOF-derived DOM 635:650 Results showed that high aromatic and hydrophobic fluorescent substances were enriched in CMOF-derived DOM and SWOF-derived DOM and enhanced over time. 35654518 6 83 theme faster 1379:1384 arg1 response 1386:1393 a faster response 1377:1393 a faster response to Pb ions 1377:1404 Regarding CMOF-derived DOM, the fulvic-like substances associated with aromatic (C=C) and carboxylic groups displayed a faster response to Pb ions on day 0. 35654518 5 84 theme humic-like 1137:1146 arg1 substances 1148:1157 humic-like substances 1137:1157 humic-like substances associated with aromatic (C=C) and phenolic groups 1137:1208 In contrast, humic-like substances associated with aromatic (C=C) and phenolic groups gave a faster response to Pb binding on day 360. 35654518 7 85 theme faster 1498:1503 arg1 response 1505:1512 a faster response 1496:1512 a faster response 1496:1512 Nonetheless, polysaccharides and humic-like associated with phenolic groups had a faster response on days 180 and 360. 35654518 9 86 theme organic 1783:1789 arg1 fertilizers 1791:1801 commercial organic fertilizers 1772:1801 commercial organic fertilizers for the amendment of soil 1772:1827 Therefore, these findings gave new insights into the long-term applications of commercial organic fertilizers for the amendment of soil. 35654518 1 87 theme correlation 481:491 arg1 spectroscopy 493:504 two-dimensional correlation spectroscopy 465:504 two-dimensional correlation spectroscopy 465:504 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 1 88 theme lead 205:208 arg1 properties 223:232 the lead (Pb) binding properties 201:232 the lead (Pb) binding properties of dissolved organic matter (DOM) 201:266 This work was to study composition characteristics and the subsequent effect on the lead (Pb) binding properties of dissolved organic matter (DOM) derived from seaweed-based (SWOF) and chicken manure organic fertilizers (CMOF) during a one-year field incubation experiment using the excitation-emission matrix-parallel factor (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2DCOS) analysis. 35654518 7 89 theme phenolic 1476:1483 arg1 groups 1485:1490 phenolic groups 1476:1490 phenolic groups 1476:1490 Nonetheless, polysaccharides and humic-like associated with phenolic groups had a faster response on days 180 and 360. 35654518 3 90 theme phenolic 680:687 arg1 groups 689:694 phenolic groups 680:694 phenolic groups in the fulvic-like substances for SWOF-derived DOM 680:745 And phenolic groups in the fulvic-like substances for SWOF-derived DOM and carboxyl groups in the humic-like substances for CMOF-derived DOM had the fastest responses over time, respectively. 35817293 3 0 theme rat 486:488 arg1 profile 506:512 rat pharmacokinetic profile 486:512 rat pharmacokinetic profile 486:512 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 2 1 theme mono-demethylated 289:305 arg1 metabolites 340:350 the mono-demethylated, non-interconverting atropisomer metabolites 285:350 the mono-demethylated, non-interconverting atropisomer metabolites 285:350 We have previously disclosed compounds such as 4, which showed good APJ agonist activity but were metabolized to the mono-demethylated, non-interconverting atropisomer metabolites. 35817293 3 2 theme metabolic 461:469 arg1 stability 471:479 metabolic stability 461:479 metabolic stability 461:479 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 1 3 theme heart 157:161 arg1 failure 163:169 heart failure 157:169 heart failure 157:169 Agonism of the apelin receptor (APJ) has demonstrated beneficial effects in models of heart failure. 35817293 2 4 theme agonist 244:250 arg1 activity 252:259 good APJ agonist activity 235:259 good APJ agonist activity 235:259 We have previously disclosed compounds such as 4, which showed good APJ agonist activity but were metabolized to the mono-demethylated, non-interconverting atropisomer metabolites. 35817293 1 5 theme failure 163:169 arg1 models 147:152 models 147:152 models of heart failure 147:169 Agonism of the apelin receptor (APJ) has demonstrated beneficial effects in models of heart failure. 35817293 3 6 link N-linked 420:427 arg1 agonists 433:440 N-linked APJ agonists 420:440 N-linked APJ agonists 420:440 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 1 7 theme apelin 86:91 arg1 receptor 93:100 apelin receptor 86:100 the apelin receptor (APJ) 82:106 Agonism of the apelin receptor (APJ) has demonstrated beneficial effects in models of heart failure. 35817293 1 7 theme apelin 86:91 arg1 APJ 103:105 APJ 103:105 APJ 103:105 Agonism of the apelin receptor (APJ) has demonstrated beneficial effects in models of heart failure. 35817293 3 8 theme series 410:415 arg1 design 375:380 design 375:380 design 375:380 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 3 8 theme series 410:415 arg1 optimization 386:397 optimization 386:397 optimization 386:397 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 1 9 theme receptor 93:100 arg1 Agonism 71:77 Agonism 71:77 Agonism of the apelin receptor (APJ) 71:106 Agonism of the apelin receptor (APJ) has demonstrated beneficial effects in models of heart failure. 35817293 3 10 with agonists 433:440 arg1 stability 471:479 metabolic stability 461:479 metabolic stability 461:479 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 3 10 with agonists 433:440 arg1 profile 506:512 rat pharmacokinetic profile 486:512 rat pharmacokinetic profile 486:512 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 3 10 with agonists 433:440 arg1 potency 452:458 good potency 447:458 good potency 447:458 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 0 11 link N-linked 26:33 arg1 agonists 61:68 N-linked hydroxypyridine-based APJ agonists 26:68 N-linked hydroxypyridine-based APJ agonists 26:68 Design and preparation of N-linked hydroxypyridine-based APJ agonists. 35817293 3 12 theme good 447:450 arg1 potency 452:458 good potency 447:458 good potency 447:458 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 3 13 theme same 547:550 arg1 cleavage 581:588 the same metabolic mono-demethylation cleavage 543:588 the same metabolic mono-demethylation cleavage 543:588 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 0 14 theme hydroxypyridine-based 35:55 arg1 agonists 61:68 N-linked hydroxypyridine-based APJ agonists 26:68 N-linked hydroxypyridine-based APJ agonists 26:68 Design and preparation of N-linked hydroxypyridine-based APJ agonists. 35817293 3 15 theme agonists 433:440 arg1 series 410:415 a novel series 402:415 a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage 402:588 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 0 16 theme N-linked 26:33 arg1 agonists 61:68 N-linked hydroxypyridine-based APJ agonists 26:68 N-linked hydroxypyridine-based APJ agonists 26:68 Design and preparation of N-linked hydroxypyridine-based APJ agonists. 35817293 3 17 theme novel 404:408 arg1 series 410:415 a novel series 402:415 a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage 402:588 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 0 18 theme agonists 61:68 arg1 preparation 11:21 preparation 11:21 preparation 11:21 Design and preparation of N-linked hydroxypyridine-based APJ agonists. 35817293 0 18 theme agonists 61:68 arg1 Design 0:5 Design 0:5 Design 0:5 Design and preparation of N-linked hydroxypyridine-based APJ agonists. 35817293 3 19 theme N-linked 420:427 arg1 agonists 433:440 N-linked APJ agonists 420:440 N-linked APJ agonists 420:440 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 3 20 theme metabolic 552:560 arg1 cleavage 581:588 the same metabolic mono-demethylation cleavage 543:588 the same metabolic mono-demethylation cleavage 543:588 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 0 21 theme APJ 57:59 arg1 agonists 61:68 N-linked hydroxypyridine-based APJ agonists 26:68 N-linked hydroxypyridine-based APJ agonists 26:68 Design and preparation of N-linked hydroxypyridine-based APJ agonists. 35817293 3 22 theme mono-demethylation 562:579 arg1 cleavage 581:588 the same metabolic mono-demethylation cleavage 543:588 the same metabolic mono-demethylation cleavage 543:588 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 2 23 theme atropisomer 328:338 arg1 metabolites 340:350 the mono-demethylated, non-interconverting atropisomer metabolites 285:350 the mono-demethylated, non-interconverting atropisomer metabolites 285:350 We have previously disclosed compounds such as 4, which showed good APJ agonist activity but were metabolized to the mono-demethylated, non-interconverting atropisomer metabolites. 35817293 2 24 theme APJ 240:242 arg1 activity 252:259 good APJ agonist activity 235:259 good APJ agonist activity 235:259 We have previously disclosed compounds such as 4, which showed good APJ agonist activity but were metabolized to the mono-demethylated, non-interconverting atropisomer metabolites. 35817293 2 25 dep mono-demethylated 289:305 arg1 non-interconverting 308:326 non-interconverting 308:326 non-interconverting 308:326 We have previously disclosed compounds such as 4, which showed good APJ agonist activity but were metabolized to the mono-demethylated, non-interconverting atropisomer metabolites. 35817293 2 26 theme good 235:238 arg1 activity 252:259 good APJ agonist activity 235:259 good APJ agonist activity 235:259 We have previously disclosed compounds such as 4, which showed good APJ agonist activity but were metabolized to the mono-demethylated, non-interconverting atropisomer metabolites. 35817293 1 27 theme beneficial 125:134 arg1 effects 136:142 beneficial effects 125:142 beneficial effects 125:142 Agonism of the apelin receptor (APJ) has demonstrated beneficial effects in models of heart failure. 35817293 3 28 theme pharmacokinetic 490:504 arg1 profile 506:512 rat pharmacokinetic profile 486:512 rat pharmacokinetic profile 486:512 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35817293 3 29 theme APJ 429:431 arg1 agonists 433:440 N-linked APJ agonists 420:440 N-linked APJ agonists 420:440 Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage. 35405815 7 0 theme alpha 1165:1169 arg1 diversity 1171:1179 the lowest alpha diversity 1154:1179 the lowest alpha diversity of bacteria composition 1154:1203 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 10 1 theme small 1755:1759 arg1 intestine 1761:1769 the small intestine 1751:1769 the small intestine 1751:1769 The small intestine was characterized by Actinobacteria and Patescibacteria at the phylum level, and KEGG pathways related to xenobiotics biodegradation and metabolism were enriched in the small intestine. 35405815 11 2 theme methionine 1974:1983 arg1 metabolism 1985:1994 methionine metabolism 1974:1994 methionine metabolism 1974:1994 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 2 3 theme high-throughput 239:253 arg1 methods 266:272 high-throughput sequencing methods 239:272 high-throughput sequencing methods 239:272 Presently, many studies have used high-throughput sequencing methods to investigate the gastrointestinal microbiome in bovines. 35405815 13 4 theme useful 2249:2254 arg1 information 2256:2266 useful information 2249:2266 useful information for the study of the gastrointestinal microbiome in bovines 2249:2326 The results can provide useful information for the study of the gastrointestinal microbiome in bovines. 35405815 4 5 theme GIT 617:619 arg1 rumen 522:526 the rumen 518:526 the rumen 518:526 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 4 5 theme GIT 617:619 arg1 rectum 602:607 rectum 602:607 rectum 602:607 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 4 5 theme GIT 617:619 arg1 abomasum 548:555 abomasum 548:555 abomasum 548:555 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 4 5 theme GIT 617:619 arg1 duodenum 558:565 duodenum 558:565 duodenum 558:565 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 4 5 theme GIT 617:619 arg1 regions 499:505 ten regions 495:505 ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT 495:619 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 4 5 theme GIT 617:619 arg1 reticulum 529:537 reticulum 529:537 reticulum 529:537 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 4 5 theme GIT 617:619 arg1 omasum 540:545 omasum 540:545 omasum 540:545 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 4 6 from regions 499:505 arg1 digesta 484:490 the digesta 480:490 the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT 480:619 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 1 7 theme bovines 196:202 arg1 status 159:164 health status 152:164 health status 152:164 The gastrointestinal microbiota greatly affects the health status and production performance of bovines. 35405815 1 7 theme bovines 196:202 arg1 performance 181:191 production performance 170:191 production performance 170:191 The gastrointestinal microbiota greatly affects the health status and production performance of bovines. 35405815 4 8 theme rRNA 793:796 arg1 gene 798:801 the 16S rRNA gene 785:801 the 16S rRNA gene 785:801 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 6 9 theme bacterial 1075:1083 arg1 composition 1085:1095 the bacterial composition 1071:1095 the bacterial composition 1071:1095 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 12 10 theme microbiota 2105:2114 arg1 heterogeneity 2088:2100 the spatial heterogeneity 2076:2100 the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds 2076:2165 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 12 11 theme study 2061:2065 arg1 results 2038:2044 The results 2034:2044 The results of the current study 2034:2065 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 2 12 theme sequencing 255:264 arg1 methods 266:272 high-throughput sequencing methods 239:272 high-throughput sequencing methods 239:272 Presently, many studies have used high-throughput sequencing methods to investigate the gastrointestinal microbiome in bovines. 35405815 13 13 theme gastrointestinal 2289:2304 arg1 microbiome 2306:2315 the gastrointestinal microbiome 2285:2315 the gastrointestinal microbiome in bovines 2285:2326 The results can provide useful information for the study of the gastrointestinal microbiome in bovines. 35405815 0 14 from Tract 73:77 arg1 Cattle 92:97 Crossbred Cattle 82:97 Crossbred Cattle 82:97 Characterization of the Microbial Communities along the Gastrointestinal Tract in Crossbred Cattle. 35405815 11 15 theme hormone 1909:1915 arg1 biosynthesis 1917:1928 steroid hormone biosynthesis 1901:1928 steroid hormone biosynthesis 1901:1928 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 8 16 theme microbiome 1322:1331 arg1 features 1333:1340 several microbiome features 1314:1340 several microbiome features 1314:1340 Three groups of GIT regions were characterized by several microbiome features. 35405815 1 17 theme health 152:157 arg1 status 159:164 health status 152:164 health status 152:164 The gastrointestinal microbiota greatly affects the health status and production performance of bovines. 35405815 6 18 theme small 950:954 arg1 groups 929:934 three groups 923:934 three groups (the stomach, small intestine, and large intestine) 923:986 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 6 18 theme small 950:954 arg1 intestine 956:964 small intestine 950:964 small intestine 950:964 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 3 19 theme crossbred 368:376 arg1 cattle 378:383 crossbred cattle 368:383 crossbred cattle across the whole gastrointestinal tract (GIT) 368:429 However, the microbiome profile of crossbred cattle across the whole gastrointestinal tract (GIT) has not been thoroughly reported. 35405815 10 20 dep xenobiotics 1692:1702 arg1 biodegradation 1704:1717 biodegradation 1704:1717 biodegradation 1704:1717 The small intestine was characterized by Actinobacteria and Patescibacteria at the phylum level, and KEGG pathways related to xenobiotics biodegradation and metabolism were enriched in the small intestine. 35405815 10 20 dep xenobiotics 1692:1702 arg1 xenobiotics 1692:1702 xenobiotics biodegradation and metabolism 1692:1732 xenobiotics biodegradation and metabolism 1692:1732 The small intestine was characterized by Actinobacteria and Patescibacteria at the phylum level, and KEGG pathways related to xenobiotics biodegradation and metabolism were enriched in the small intestine. 35405815 10 20 dep xenobiotics 1692:1702 arg1 metabolism 1723:1732 metabolism 1723:1732 metabolism 1723:1732 The small intestine was characterized by Actinobacteria and Patescibacteria at the phylum level, and KEGG pathways related to xenobiotics biodegradation and metabolism were enriched in the small intestine. 35405815 7 21 theme lowest 1158:1163 arg1 diversity 1171:1179 the lowest alpha diversity 1154:1179 the lowest alpha diversity of bacteria composition 1154:1203 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 11 22 theme acid 1940:1943 arg1 metabolism 1945:1954 linoleic acid metabolism 1931:1954 linoleic acid metabolism 1931:1954 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 0 23 theme Crossbred 82:90 arg1 Cattle 92:97 Crossbred Cattle 82:97 Crossbred Cattle 82:97 Characterization of the Microbial Communities along the Gastrointestinal Tract in Crossbred Cattle. 35405815 5 24 theme genome 843:848 arg1 orthologs 815:823 Functional orthologs 804:823 Functional orthologs of the microbiota genome 804:848 Functional orthologs of the microbiota genome were predicted and analyzed. 35405815 3 25 theme whole 396:400 arg1 GIT 426:428 GIT 426:428 GIT 426:428 However, the microbiome profile of crossbred cattle across the whole gastrointestinal tract (GIT) has not been thoroughly reported. 35405815 3 25 theme whole 396:400 arg1 tract 419:423 the whole gastrointestinal tract 392:423 the whole gastrointestinal tract (GIT) 392:429 However, the microbiome profile of crossbred cattle across the whole gastrointestinal tract (GIT) has not been thoroughly reported. 35405815 8 26 theme GIT 1280:1282 arg1 regions 1284:1290 GIT regions 1280:1290 GIT regions 1280:1290 Three groups of GIT regions were characterized by several microbiome features. 35405815 8 27 theme several 1314:1320 arg1 features 1333:1340 several microbiome features 1314:1340 several microbiome features 1314:1340 Three groups of GIT regions were characterized by several microbiome features. 35405815 7 28 theme small 1134:1138 arg1 intestine 1140:1148 small intestine 1134:1148 small intestine 1134:1148 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 6 29 theme functional 1101:1110 arg1 profile 1112:1118 functional profile 1101:1118 functional profile 1101:1118 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 9 30 theme vitamins 1490:1497 arg1 metabolism 1462:1471 the metabolism 1458:1471 the metabolism of cofactors and vitamins 1458:1497 The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. 35405815 9 30 theme vitamins 1490:1497 arg1 biosynthesis 1507:1518 glycan biosynthesis 1500:1518 glycan biosynthesis 1500:1518 The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. 35405815 9 30 theme vitamins 1490:1497 arg1 metabolism 1525:1534 metabolism 1525:1534 metabolism 1525:1534 The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. 35405815 6 31 theme large 971:975 arg1 intestine 977:985 large intestine 971:985 large intestine 971:985 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 6 31 theme large 971:975 arg1 groups 929:934 three groups 923:934 three groups (the stomach, small intestine, and large intestine) 923:986 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 9 32 theme glycan 1500:1505 arg1 biosynthesis 1507:1518 glycan biosynthesis 1500:1518 glycan biosynthesis 1500:1518 The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. 35405815 6 33 theme principal 991:999 arg1 PCoA 1022:1025 PCoA 1022:1025 PCoA 1022:1025 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 6 33 theme principal 991:999 arg1 analysis 1012:1019 principal coordinate analysis 991:1019 principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile 991:1118 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 11 34 theme family 1858:1863 arg1 level 1865:1869 the family level 1854:1869 the family level 1854:1869 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 1 35 dep status 159:164 arg1 the 148:150 the 148:150 the 148:150 The gastrointestinal microbiota greatly affects the health status and production performance of bovines. 35405815 7 36 theme functional 1240:1249 arg1 composition 1251:1261 the functional composition 1236:1261 the functional composition 1236:1261 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 12 37 theme × 2144:2144 arg1 crossbreeds 2155:2165 Simmental × Holstein crossbreeds 2134:2165 Simmental × Holstein crossbreeds 2134:2165 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 11 38 theme KEGG 1876:1879 arg1 biosynthesis 1917:1928 steroid hormone biosynthesis 1901:1928 steroid hormone biosynthesis 1901:1928 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 11 38 theme KEGG 1876:1879 arg1 pathways 1881:1888 KEGG pathways 1876:1888 KEGG pathways 1876:1888 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 11 38 theme KEGG 1876:1879 arg1 metabolism 1945:1954 linoleic acid metabolism 1931:1954 linoleic acid metabolism 1931:1954 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 11 38 theme KEGG 1876:1879 arg1 cysteine 1961:1968 cysteine 1961:1968 cysteine 1961:1968 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 11 38 theme KEGG 1876:1879 arg1 metabolism 1985:1994 methionine metabolism 1974:1994 methionine metabolism 1974:1994 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 0 39 theme Communities 34:44 arg1 Characterization 0:15 Characterization 0:15 Characterization of the Microbial Communities along the Gastrointestinal Tract in Crossbred Cattle. 0:98 Characterization of the Microbial Communities along the Gastrointestinal Tract in Crossbred Cattle. 35405815 4 40 theme regions 774:780 arg1 sequencing 750:759 sequencing 750:759 sequencing of the V3-V4 regions of the 16S rRNA gene 750:801 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 7 41 theme alpha 1217:1221 arg1 diversity 1223:1231 highest alpha diversity 1209:1231 highest alpha diversity of the functional composition 1209:1261 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 10 42 theme phylum 1649:1654 arg1 level 1656:1660 the phylum level 1645:1660 the phylum level 1645:1660 The small intestine was characterized by Actinobacteria and Patescibacteria at the phylum level, and KEGG pathways related to xenobiotics biodegradation and metabolism were enriched in the small intestine. 35405815 10 43 theme related 1681:1687 arg1 pathways 1672:1679 KEGG pathways 1667:1679 KEGG pathways related to xenobiotics biodegradation and metabolism 1667:1732 The small intestine was characterized by Actinobacteria and Patescibacteria at the phylum level, and KEGG pathways related to xenobiotics biodegradation and metabolism were enriched in the small intestine. 35405815 7 44 theme bacteria 1184:1191 arg1 composition 1193:1203 bacteria composition 1184:1203 bacteria composition 1184:1203 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 10 45 theme KEGG 1667:1670 arg1 pathways 1672:1679 KEGG pathways 1667:1679 KEGG pathways related to xenobiotics biodegradation and metabolism 1667:1732 The small intestine was characterized by Actinobacteria and Patescibacteria at the phylum level, and KEGG pathways related to xenobiotics biodegradation and metabolism were enriched in the small intestine. 35405815 12 46 from GIT 2127:2129 arg1 crossbreeds 2155:2165 Simmental × Holstein crossbreeds 2134:2165 Simmental × Holstein crossbreeds 2134:2165 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 4 47 theme gene 798:801 arg1 regions 774:780 the V3-V4 regions 764:780 the V3-V4 regions of the 16S rRNA gene 764:801 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 5 48 theme microbiota 832:841 arg1 genome 843:848 the microbiota genome 828:848 the microbiota genome 828:848 Functional orthologs of the microbiota genome were predicted and analyzed. 35405815 13 49 theme microbiome 2306:2315 arg1 study 2276:2280 the study 2272:2280 the study of the gastrointestinal microbiome in bovines 2272:2326 The results can provide useful information for the study of the gastrointestinal microbiome in bovines. 35405815 12 50 theme spatial 2080:2086 arg1 heterogeneity 2088:2100 the spatial heterogeneity 2076:2100 the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds 2076:2165 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 5 51 theme Functional 804:813 arg1 orthologs 815:823 Functional orthologs 804:823 Functional orthologs of the microbiota genome 804:848 Functional orthologs of the microbiota genome were predicted and analyzed. 35405815 4 52 theme 16S 789:791 arg1 gene 798:801 the 16S rRNA gene 785:801 the 16S rRNA gene 785:801 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 2 53 used used 234:237 arg2 studies 221:227 many studies 216:227 many studies 216:227 Presently, many studies have used high-throughput sequencing methods to investigate the gastrointestinal microbiome in bovines. 35405815 4 54 theme V3-V4 768:772 arg1 regions 774:780 the V3-V4 regions 764:780 the V3-V4 regions of the 16S rRNA gene 764:801 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 9 55 theme phylum 1415:1420 arg1 level 1422:1426 the phylum level 1411:1426 the phylum level 1411:1426 The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. 35405815 13 56 from study 2276:2280 arg1 bovines 2320:2326 bovines 2320:2326 bovines 2320:2326 The results can provide useful information for the study of the gastrointestinal microbiome in bovines. 35405815 9 57 theme cofactors 1476:1484 arg1 metabolism 1462:1471 the metabolism 1458:1471 the metabolism of cofactors and vitamins 1458:1497 The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. 35405815 9 57 theme cofactors 1476:1484 arg1 biosynthesis 1507:1518 glycan biosynthesis 1500:1518 glycan biosynthesis 1500:1518 The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. 35405815 9 57 theme cofactors 1476:1484 arg1 metabolism 1525:1534 metabolism 1525:1534 metabolism 1525:1534 The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. 35405815 12 58 theme current 2053:2059 arg1 study 2061:2065 the current study 2049:2065 the current study 2049:2065 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 10 59 theme small 1570:1574 arg1 intestine 1576:1584 The small intestine 1566:1584 The small intestine 1566:1584 The small intestine was characterized by Actinobacteria and Patescibacteria at the phylum level, and KEGG pathways related to xenobiotics biodegradation and metabolism were enriched in the small intestine. 35405815 6 60 theme Bray-Curtis 1037:1047 arg1 dissimilarity 1049:1061 Bray-Curtis dissimilarity 1037:1061 Bray-Curtis dissimilarity in both the bacterial composition and functional profile 1037:1118 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 12 61 gly heterogeneity 2088:2100 arg1 microbiota 2105:2114 microbiota 2105:2114 microbiota 2105:2114 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 11 62 theme large 2017:2021 arg1 intestine 2023:2031 the large intestine 2013:2031 the large intestine 2013:2031 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 11 63 theme steroid 1901:1907 arg1 biosynthesis 1917:1928 steroid hormone biosynthesis 1901:1928 steroid hormone biosynthesis 1901:1928 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 9 64 theme KEGG 1433:1436 arg1 pathways 1438:1445 KEGG pathways 1433:1445 KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism 1433:1534 The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. 35405815 3 65 theme microbiome 346:355 arg1 profile 357:363 the microbiome profile 342:363 the microbiome profile of crossbred cattle across the whole gastrointestinal tract (GIT) 342:429 However, the microbiome profile of crossbred cattle across the whole gastrointestinal tract (GIT) has not been thoroughly reported. 35405815 7 66 from intestine 1140:1148 arg1 Samples 1121:1127 Samples 1121:1127 Samples from small intestine 1121:1148 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 11 67 theme large 1776:1780 arg1 intestine 1782:1790 The large intestine 1772:1790 The large intestine 1772:1790 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 2 68 theme gastrointestinal 293:308 arg1 microbiome 310:319 the gastrointestinal microbiome 289:319 the gastrointestinal microbiome in bovines 289:330 Presently, many studies have used high-throughput sequencing methods to investigate the gastrointestinal microbiome in bovines. 35405815 9 69 theme related 1447:1453 arg1 pathways 1438:1445 KEGG pathways 1433:1445 KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism 1433:1534 The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. 35405815 2 70 from microbiome 310:319 arg1 bovines 324:330 bovines 324:330 bovines 324:330 Presently, many studies have used high-throughput sequencing methods to investigate the gastrointestinal microbiome in bovines. 35405815 12 71 theme different 2206:2214 arg1 regions 2216:2222 different regions 2206:2222 different regions 2206:2222 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 11 72 theme linoleic 1931:1938 arg1 acid 1940:1943 linoleic acid 1931:1943 linoleic acid metabolism 1931:1954 The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. 35405815 3 73 theme cattle 378:383 arg1 profile 357:363 the microbiome profile 342:363 the microbiome profile of crossbred cattle across the whole gastrointestinal tract (GIT) 342:429 However, the microbiome profile of crossbred cattle across the whole gastrointestinal tract (GIT) has not been thoroughly reported. 35405815 6 74 dep groups 929:934 arg1 intestine 977:985 large intestine 971:985 large intestine 971:985 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 6 74 dep groups 929:934 arg1 groups 929:934 three groups 923:934 three groups (the stomach, small intestine, and large intestine) 923:986 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 6 74 dep groups 929:934 arg1 stomach 941:947 the stomach 937:947 the stomach 937:947 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 6 74 dep groups 929:934 arg1 intestine 956:964 small intestine 950:964 small intestine 950:964 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 1 75 theme production 170:179 arg1 performance 181:191 production performance 170:191 production performance 170:191 The gastrointestinal microbiota greatly affects the health status and production performance of bovines. 35405815 13 76 from bovines 2320:2326 arg1 study 2276:2280 the study 2272:2280 the study of the gastrointestinal microbiome in bovines 2272:2326 The results can provide useful information for the study of the gastrointestinal microbiome in bovines. 35405815 3 77 theme gastrointestinal 402:417 arg1 GIT 426:428 GIT 426:428 GIT 426:428 However, the microbiome profile of crossbred cattle across the whole gastrointestinal tract (GIT) has not been thoroughly reported. 35405815 3 77 theme gastrointestinal 402:417 arg1 tract 419:423 the whole gastrointestinal tract 392:423 the whole gastrointestinal tract (GIT) 392:429 However, the microbiome profile of crossbred cattle across the whole gastrointestinal tract (GIT) has not been thoroughly reported. 35405815 4 78 theme microbial 704:712 arg1 DNA 714:716 microbial DNA 704:716 microbial DNA 704:716 In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3-V4 regions of the 16S rRNA gene. 35405815 6 79 theme coordinate 1001:1010 arg1 PCoA 1022:1025 PCoA 1022:1025 PCoA 1022:1025 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 6 79 theme coordinate 1001:1010 arg1 analysis 1012:1019 principal coordinate analysis 991:1019 principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile 991:1118 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 8 80 theme regions 1284:1290 arg1 regions 1284:1290 GIT regions 1280:1290 GIT regions 1280:1290 Three groups of GIT regions were characterized by several microbiome features. 35405815 8 80 theme regions 1284:1290 arg1 groups 1270:1275 Three groups 1264:1275 Three groups of GIT regions 1264:1290 Three groups of GIT regions were characterized by several microbiome features. 35405815 7 81 theme composition 1251:1261 arg1 diversity 1223:1231 highest alpha diversity 1209:1231 highest alpha diversity of the functional composition 1209:1261 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 7 81 theme composition 1251:1261 arg1 diversity 1171:1179 the lowest alpha diversity 1154:1179 the lowest alpha diversity of bacteria composition 1154:1203 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 0 82 theme Microbial 24:32 arg1 Communities 34:44 the Microbial Communities 20:44 the Microbial Communities 20:44 Characterization of the Microbial Communities along the Gastrointestinal Tract in Crossbred Cattle. 35405815 1 83 theme gastrointestinal 104:119 arg1 microbiota 121:130 The gastrointestinal microbiota 100:130 The gastrointestinal microbiota 100:130 The gastrointestinal microbiota greatly affects the health status and production performance of bovines. 35405815 12 84 theme microbial 2182:2190 arg1 biomarkers 2192:2201 microbial biomarkers 2182:2201 microbial biomarkers of different regions 2182:2222 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 12 85 theme Simmental 2134:2142 arg1 crossbreeds 2155:2165 Simmental × Holstein crossbreeds 2134:2165 Simmental × Holstein crossbreeds 2134:2165 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 0 86 theme Gastrointestinal 56:71 arg1 Tract 73:77 the Gastrointestinal Tract 52:77 the Gastrointestinal Tract in Crossbred Cattle 52:97 Characterization of the Microbial Communities along the Gastrointestinal Tract in Crossbred Cattle. 35405815 7 87 theme highest 1209:1215 arg1 diversity 1223:1231 highest alpha diversity 1209:1231 highest alpha diversity of the functional composition 1209:1261 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 12 88 theme Holstein 2146:2153 arg1 crossbreeds 2155:2165 Simmental × Holstein crossbreeds 2134:2165 Simmental × Holstein crossbreeds 2134:2165 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 6 89 from dissimilarity 1049:1061 arg1 composition 1085:1095 the bacterial composition 1071:1095 the bacterial composition 1071:1095 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 6 89 from dissimilarity 1049:1061 arg1 profile 1112:1118 functional profile 1101:1118 functional profile 1101:1118 We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarity in both the bacterial composition and functional profile. 35405815 7 90 theme composition 1193:1203 arg1 diversity 1223:1231 highest alpha diversity 1209:1231 highest alpha diversity of the functional composition 1209:1261 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 7 90 theme composition 1193:1203 arg1 diversity 1171:1179 the lowest alpha diversity 1154:1179 the lowest alpha diversity of bacteria composition 1154:1203 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 12 91 theme regions 2216:2222 arg1 biomarkers 2192:2201 microbial biomarkers 2182:2201 microbial biomarkers of different regions 2182:2222 The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. 35405815 2 92 theme many 216:219 arg1 studies 221:227 many studies 216:227 many studies 216:227 Presently, many studies have used high-throughput sequencing methods to investigate the gastrointestinal microbiome in bovines. 35405815 7 93 contain had 1150:1152 arg2 diversity 1223:1231 highest alpha diversity 1209:1231 highest alpha diversity of the functional composition 1209:1261 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 7 93 contain had 1150:1152 arg1 Samples 1121:1127 Samples 1121:1127 Samples from small intestine 1121:1148 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 7 93 contain had 1150:1152 arg2 diversity 1171:1179 the lowest alpha diversity 1154:1179 the lowest alpha diversity of bacteria composition 1154:1203 Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. 35405815 13 94 from microbiome 2306:2315 arg1 bovines 2320:2326 bovines 2320:2326 bovines 2320:2326 The results can provide useful information for the study of the gastrointestinal microbiome in bovines. 36082156 6 0 theme months 922:927 arg1 feces 903:907 yak feces 899:907 yak feces of different months old 899:931 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 4 1 theme dynamic 485:491 arg1 distribution 493:504 dynamic distribution 485:504 dynamic distribution 485:504 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 11 2 theme microbial 1832:1840 arg1 composition 1842:1852 microbial composition 1832:1852 microbial composition 1832:1852 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 1 3 theme stressful 153:161 arg1 periods 163:169 the most stressful periods 144:169 the most stressful periods in yak growth 144:183 Weaning is one of the most stressful periods in yak growth. 36082156 10 4 contain has 1504:1506 arg1 weaning 1496:1502 weaning 1496:1502 weaning 1496:1502 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 4 contain has 1504:1506 arg2 impact 1522:1527 a significant impact 1508:1527 a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism 1508:1760 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 4 5 theme fungal 558:563 arg1 communities 565:575 yak fecal, bacterial, and fungal communities 532:575 yak fecal, bacterial, and fungal communities 532:575 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 7 6 dep abundance 938:946 arg1 The 934:936 The 934:936 The 934:936 The abundance and proportion of bacteria Firmicutes, Bacteroidetes, 5-7N15, and fungi Mucoromyceta changed significantly before and after weaning. 36082156 11 7 theme different 1879:1887 arg1 months 1889:1894 different months 1879:1894 different months 1879:1894 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 9 8 theme primary 1270:1276 arg1 pathways 1278:1285 primary pathways 1270:1285 primary pathways 1270:1285 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 2 9 theme potential 256:264 arg1 function 266:273 potential function 256:273 potential function 256:273 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 12 10 from changes 2036:2042 arg1 structure 2067:2075 structure 2067:2075 structure 2067:2075 In general, the changes in the composition and structure of yak fecal microflora may reflect the adaptability of the intestinal microbiota. 36082156 12 10 from changes 2036:2042 arg1 composition 2051:2061 composition 2051:2061 composition 2051:2061 In general, the changes in the composition and structure of yak fecal microflora may reflect the adaptability of the intestinal microbiota. 36082156 11 11 theme months 1889:1894 arg1 groups 1869:1874 sample groups 1862:1874 sample groups of different months 1862:1894 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 11 11 theme months 1889:1894 arg1 months 1889:1894 different months 1879:1894 different months 1879:1894 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 10 12 theme acid 1621:1624 arg1 metabolism 1626:1635 amino acid metabolism 1615:1635 amino acid metabolism 1615:1635 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 9 13 theme significant 1302:1312 arg1 impact 1314:1319 a significant impact 1300:1319 a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems 1300:1447 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 2 14 theme microbial 220:228 arg1 diversity 230:238 microbial diversity 220:238 microbial diversity 220:238 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 1 15 from periods 163:169 arg1 growth 178:183 yak growth 174:183 yak growth 174:183 Weaning is one of the most stressful periods in yak growth. 36082156 12 16 theme microbiota 2148:2157 arg1 adaptability 2117:2128 the adaptability 2113:2128 the adaptability of the intestinal microbiota 2113:2157 In general, the changes in the composition and structure of yak fecal microflora may reflect the adaptability of the intestinal microbiota. 36082156 0 17 theme Potential 59:67 arg1 Analysis 78:85 Potential Function Analysis 59:85 Potential Function Analysis of Yak Feces before and after Weaning 59:123 Comparison of Bacterial and Fungal Community Structure and Potential Function Analysis of Yak Feces before and after Weaning. 36082156 2 18 theme weaning 209:215 arg1 impact 199:204 the impact 195:204 the impact of weaning on microbial diversity, structure, and potential function of yak feces 195:286 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 2 18 theme weaning 209:215 arg1 clear 295:299 clear 295:299 clear 295:299 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 4 19 from distribution 493:504 arg1 month 585:589 each month 580:589 each month 580:589 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 9 20 theme environmental 1344:1356 arg1 processes 1333:1341 cellular processes 1324:1341 cellular processes 1324:1341 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 20 theme environmental 1344:1356 arg1 processing 1370:1379 environmental information processing 1344:1379 environmental information processing 1344:1379 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 0 21 theme Yak 90:92 arg1 Feces 94:98 Yak Feces 90:98 Yak Feces before and after Weaning 90:123 Comparison of Bacterial and Fungal Community Structure and Potential Function Analysis of Yak Feces before and after Weaning. 36082156 12 22 theme yak 2080:2082 arg1 microflora 2090:2099 yak fecal microflora 2080:2099 yak fecal microflora 2080:2099 In general, the changes in the composition and structure of yak fecal microflora may reflect the adaptability of the intestinal microbiota. 36082156 3 23 dep aged 334:337 arg1 old 361:363 old 361:363 old 361:363 In this study, 12 Xinjiang yaks aged 3, 4, 5, and 6 months old were selected to collect fresh feces before and after weaning. 36082156 6 24 dep enriched 887:894 arg1 level 700:704 the phylum level 689:704 the phylum level 689:704 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 6 24 dep enriched 887:894 arg1 Firmicutes 707:716 Firmicutes 707:716 Firmicutes 707:716 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 6 24 dep enriched 887:894 arg1 Basidiomycota 750:762 Basidiomycota 750:762 Basidiomycota 750:762 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 6 24 dep enriched 887:894 arg1 level 782:786 the genus level 772:786 the genus level 772:786 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 6 24 dep enriched 887:894 arg1 Bacteroidetes 719:731 Bacteroidetes 719:731 Bacteroidetes 719:731 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 6 24 dep enriched 887:894 arg1 Ascomycota 734:743 Ascomycota 734:743 Ascomycota 734:743 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 10 25 theme pathways 1486:1493 arg1 level 1457:1461 the level 1453:1461 the level of secondary metabolic pathways 1453:1493 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 7 26 theme fungi 1014:1018 arg1 abundance 938:946 abundance 938:946 abundance 938:946 The abundance and proportion of bacteria Firmicutes, Bacteroidetes, 5-7N15, and fungi Mucoromyceta changed significantly before and after weaning. 36082156 7 26 theme fungi 1014:1018 arg1 proportion 952:961 proportion 952:961 proportion 952:961 The abundance and proportion of bacteria Firmicutes, Bacteroidetes, 5-7N15, and fungi Mucoromyceta changed significantly before and after weaning. 36082156 9 27 theme genetic 1382:1388 arg1 processing 1402:1411 genetic information processing 1382:1411 genetic information processing 1382:1411 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 27 theme genetic 1382:1388 arg1 processes 1333:1341 cellular processes 1324:1341 cellular processes 1324:1341 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 3 28 theme Xinjiang 320:327 arg1 yaks 329:332 12 Xinjiang yaks 317:332 12 Xinjiang yaks aged 3, 4, 5, and 6 months old 317:363 In this study, 12 Xinjiang yaks aged 3, 4, 5, and 6 months old were selected to collect fresh feces before and after weaning. 36082156 12 29 theme microflora 2090:2099 arg1 structure 2067:2075 structure 2067:2075 structure 2067:2075 In general, the changes in the composition and structure of yak fecal microflora may reflect the adaptability of the intestinal microbiota. 36082156 12 29 theme microflora 2090:2099 arg1 composition 2051:2061 composition 2051:2061 composition 2051:2061 In general, the changes in the composition and structure of yak fecal microflora may reflect the adaptability of the intestinal microbiota. 36082156 0 30 theme Function 69:76 arg1 Analysis 78:85 Potential Function Analysis 59:85 Potential Function Analysis of Yak Feces before and after Weaning 59:123 Comparison of Bacterial and Fungal Community Structure and Potential Function Analysis of Yak Feces before and after Weaning. 36082156 10 31 theme secondary 1466:1474 arg1 pathways 1486:1493 secondary metabolic pathways 1466:1493 secondary metabolic pathways 1466:1493 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 0 32 theme Bacterial 14:22 arg1 Structure 45:53 Bacterial and Fungal Community Structure 14:53 Bacterial and Fungal Community Structure 14:53 Comparison of Bacterial and Fungal Community Structure and Potential Function Analysis of Yak Feces before and after Weaning. 36082156 0 33 theme Fungal 28:33 arg1 Structure 45:53 Bacterial and Fungal Community Structure 14:53 Bacterial and Fungal Community Structure 14:53 Comparison of Bacterial and Fungal Community Structure and Potential Function Analysis of Yak Feces before and after Weaning. 36082156 5 34 theme significant 655:665 arg1 impact 667:672 a significant impact 653:672 a significant impact 653:672 The study found that the richness of fungi had a significant impact on weaning. 36082156 3 35 theme aged 334:337 arg1 yaks 329:332 12 Xinjiang yaks 317:332 12 Xinjiang yaks aged 3, 4, 5, and 6 months old 317:363 In this study, 12 Xinjiang yaks aged 3, 4, 5, and 6 months old were selected to collect fresh feces before and after weaning. 36082156 10 36 theme cell 1532:1535 arg1 motility 1537:1544 cell motility 1532:1544 cell motility 1532:1544 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 7 37 theme bacteria 966:973 arg1 abundance 938:946 abundance 938:946 abundance 938:946 The abundance and proportion of bacteria Firmicutes, Bacteroidetes, 5-7N15, and fungi Mucoromyceta changed significantly before and after weaning. 36082156 7 37 theme bacteria 966:973 arg1 proportion 952:961 proportion 952:961 proportion 952:961 The abundance and proportion of bacteria Firmicutes, Bacteroidetes, 5-7N15, and fungi Mucoromyceta changed significantly before and after weaning. 36082156 10 38 theme polyketides 1703:1713 arg1 metabolism 1662:1671 metabolism 1662:1671 metabolism 1662:1671 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 metabolism 1626:1635 amino acid metabolism 1615:1635 amino acid metabolism 1615:1635 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 metabolism 1751:1760 metabolism 1751:1760 metabolism 1751:1760 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 transduction 1554:1565 signal transduction 1547:1565 signal transduction 1547:1565 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 metabolism 1674:1683 metabolism 1674:1683 metabolism of terpenoids and polyketides 1674:1713 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 degradation 1589:1599 degradation 1589:1599 degradation 1589:1599 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 xenobiotics 1720:1730 xenobiotics biodegradation and metabolism 1720:1760 xenobiotics biodegradation and metabolism 1720:1760 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 translation 1602:1612 translation 1602:1612 translation 1602:1612 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 biodegradation 1732:1745 biodegradation 1732:1745 biodegradation 1732:1745 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 biosynthesis 1645:1656 glycan biosynthesis 1638:1656 glycan biosynthesis 1638:1656 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 folding 1568:1574 folding 1568:1574 folding 1568:1574 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 sorting 1577:1583 sorting 1577:1583 sorting 1577:1583 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 38 theme polyketides 1703:1713 arg1 motility 1537:1544 cell motility 1532:1544 cell motility 1532:1544 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 9 39 theme microbial 1216:1224 arg1 function 1226:1233 fecal microbial function 1210:1233 fecal microbial function 1210:1233 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 10 40 theme terpenoids 1688:1697 arg1 metabolism 1662:1671 metabolism 1662:1671 metabolism 1662:1671 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 metabolism 1626:1635 amino acid metabolism 1615:1635 amino acid metabolism 1615:1635 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 metabolism 1751:1760 metabolism 1751:1760 metabolism 1751:1760 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 transduction 1554:1565 signal transduction 1547:1565 signal transduction 1547:1565 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 metabolism 1674:1683 metabolism 1674:1683 metabolism of terpenoids and polyketides 1674:1713 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 degradation 1589:1599 degradation 1589:1599 degradation 1589:1599 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 xenobiotics 1720:1730 xenobiotics biodegradation and metabolism 1720:1760 xenobiotics biodegradation and metabolism 1720:1760 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 translation 1602:1612 translation 1602:1612 translation 1602:1612 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 biodegradation 1732:1745 biodegradation 1732:1745 biodegradation 1732:1745 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 biosynthesis 1645:1656 glycan biosynthesis 1638:1656 glycan biosynthesis 1638:1656 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 folding 1568:1574 folding 1568:1574 folding 1568:1574 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 sorting 1577:1583 sorting 1577:1583 sorting 1577:1583 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 40 theme terpenoids 1688:1697 arg1 motility 1537:1544 cell motility 1532:1544 cell motility 1532:1544 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 6 41 theme genus 776:780 arg1 level 782:786 the genus level 772:786 the genus level 772:786 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 6 42 theme old 929:931 arg1 months 922:927 different months 912:927 different months old 912:931 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 4 43 theme potential 510:518 arg1 function 520:527 potential function 510:527 potential function 510:527 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 10 44 from impact 1522:1527 arg1 metabolism 1626:1635 amino acid metabolism 1615:1635 amino acid metabolism 1615:1635 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 44 from impact 1522:1527 arg1 metabolism 1751:1760 metabolism 1751:1760 metabolism 1751:1760 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 44 from impact 1522:1527 arg1 transduction 1554:1565 signal transduction 1547:1565 signal transduction 1547:1565 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 44 from impact 1522:1527 arg1 metabolism 1674:1683 metabolism 1674:1683 metabolism of terpenoids and polyketides 1674:1713 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 44 from impact 1522:1527 arg1 xenobiotics 1720:1730 xenobiotics biodegradation and metabolism 1720:1760 xenobiotics biodegradation and metabolism 1720:1760 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 44 from impact 1522:1527 arg1 translation 1602:1612 translation 1602:1612 translation 1602:1612 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 44 from impact 1522:1527 arg1 biodegradation 1732:1745 biodegradation 1732:1745 biodegradation 1732:1745 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 44 from impact 1522:1527 arg1 biosynthesis 1645:1656 glycan biosynthesis 1638:1656 glycan biosynthesis 1638:1656 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 44 from impact 1522:1527 arg1 folding 1568:1574 folding 1568:1574 folding 1568:1574 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 44 from impact 1522:1527 arg1 sorting 1577:1583 sorting 1577:1583 sorting 1577:1583 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 44 from impact 1522:1527 arg1 motility 1537:1544 cell motility 1532:1544 cell motility 1532:1544 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 6 45 theme different 912:920 arg1 months 922:927 different months 912:927 different months old 912:931 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 11 46 theme functional 1934:1943 arg1 pathways 1945:1952 functional pathways 1934:1952 functional pathways 1934:1952 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 11 47 from differences 1793:1803 arg1 composition 1842:1852 microbial composition 1832:1852 microbial composition 1832:1852 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 11 47 from differences 1793:1803 arg1 pathways 1819:1826 functional pathways 1808:1826 functional pathways 1808:1826 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 0 48 theme Structure 45:53 arg1 Analysis 78:85 Potential Function Analysis 59:85 Potential Function Analysis of Yak Feces before and after Weaning 59:123 Comparison of Bacterial and Fungal Community Structure and Potential Function Analysis of Yak Feces before and after Weaning. 36082156 0 48 theme Structure 45:53 arg1 Comparison 0:9 Comparison 0:9 Comparison of Bacterial and Fungal Community Structure 0:53 Comparison of Bacterial and Fungal Community Structure and Potential Function Analysis of Yak Feces before and after Weaning. 36082156 11 49 theme abundance 1974:1982 arg1 differences 1984:1994 the abundance differences 1970:1994 the abundance differences of some microorganisms 1970:2017 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 9 50 from impact 1314:1319 arg1 processes 1333:1341 cellular processes 1324:1341 cellular processes 1324:1341 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 50 from impact 1314:1319 arg1 systems 1441:1447 organismal systems 1430:1447 organismal systems 1430:1447 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 50 from impact 1314:1319 arg1 metabolism 1414:1423 metabolism 1414:1423 metabolism 1414:1423 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 50 from impact 1314:1319 arg1 processing 1370:1379 environmental information processing 1344:1379 environmental information processing 1344:1379 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 50 from impact 1314:1319 arg1 processing 1402:1411 genetic information processing 1382:1411 genetic information processing 1382:1411 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 4 51 theme bacterial 543:551 arg1 communities 565:575 yak fecal, bacterial, and fungal communities 532:575 yak fecal, bacterial, and fungal communities 532:575 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 2 52 theme yak 278:280 arg1 feces 282:286 yak feces 278:286 yak feces 278:286 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 1 53 theme periods 163:169 arg1 periods 163:169 the most stressful periods 144:169 the most stressful periods in yak growth 144:183 Weaning is one of the most stressful periods in yak growth. 36082156 1 53 theme periods 163:169 arg1 one 137:139 one 137:139 one 137:139 Weaning is one of the most stressful periods in yak growth. 36082156 11 54 theme sample 1862:1867 arg1 groups 1869:1874 sample groups 1862:1874 sample groups of different months 1862:1894 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 11 54 theme sample 1862:1867 arg1 months 1889:1894 different months 1879:1894 different months 1879:1894 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 1 55 theme yak 174:176 arg1 growth 178:183 yak growth 174:183 yak growth 174:183 Weaning is one of the most stressful periods in yak growth. 36082156 12 56 dep composition 2051:2061 arg1 the 2047:2049 the 2047:2049 the 2047:2049 In general, the changes in the composition and structure of yak fecal microflora may reflect the adaptability of the intestinal microbiota. 36082156 11 57 located found 1904:1908 arg2 it 1897:1898 it 1897:1898 it 1897:1898 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 11 57 located found 1904:1908 arg1 addition 1766:1773 addition 1766:1773 addition 1766:1773 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 4 58 theme fecal 536:540 arg1 communities 565:575 yak fecal, bacterial, and fungal communities 532:575 yak fecal, bacterial, and fungal communities 532:575 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 10 59 theme amino 1615:1619 arg1 metabolism 1626:1635 amino acid metabolism 1615:1635 amino acid metabolism 1615:1635 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 12 60 theme intestinal 2137:2146 arg1 microbiota 2148:2157 the intestinal microbiota 2133:2157 the intestinal microbiota 2133:2157 In general, the changes in the composition and structure of yak fecal microflora may reflect the adaptability of the intestinal microbiota. 36082156 11 61 theme functional 1808:1817 arg1 pathways 1819:1826 functional pathways 1808:1826 functional pathways 1808:1826 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 4 62 from function 520:527 arg1 month 585:589 each month 580:589 each month 580:589 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 4 63 dep distribution 493:504 arg1 the 481:483 the 481:483 the 481:483 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 10 64 theme glycan 1638:1643 arg1 biosynthesis 1645:1656 glycan biosynthesis 1638:1656 glycan biosynthesis 1638:1656 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 9 65 theme pathways 1278:1285 arg1 level 1261:1265 the level 1257:1265 the level of primary pathways 1257:1285 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 66 theme cellular 1324:1331 arg1 processes 1333:1341 cellular processes 1324:1341 cellular processes 1324:1341 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 66 theme cellular 1324:1331 arg1 systems 1441:1447 organismal systems 1430:1447 organismal systems 1430:1447 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 66 theme cellular 1324:1331 arg1 metabolism 1414:1423 metabolism 1414:1423 metabolism 1414:1423 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 66 theme cellular 1324:1331 arg1 processing 1370:1379 environmental information processing 1344:1379 environmental information processing 1344:1379 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 66 theme cellular 1324:1331 arg1 processing 1402:1411 genetic information processing 1382:1411 genetic information processing 1382:1411 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 5 67 contain had 649:651 arg1 richness 631:638 the richness 627:638 the richness of fungi 627:647 The study found that the richness of fungi had a significant impact on weaning. 36082156 5 67 contain had 649:651 arg2 impact 667:672 a significant impact 653:672 a significant impact 653:672 The study found that the richness of fungi had a significant impact on weaning. 36082156 4 68 theme communities 565:575 arg1 distribution 493:504 dynamic distribution 485:504 dynamic distribution 485:504 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 4 68 theme communities 565:575 arg1 function 520:527 potential function 510:527 potential function 510:527 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 11 69 from differences 1919:1929 arg1 pathways 1945:1952 functional pathways 1934:1952 functional pathways 1934:1952 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 5 70 theme fungi 643:647 arg1 richness 631:638 the richness 627:638 the richness of fungi 627:647 The study found that the richness of fungi had a significant impact on weaning. 36082156 8 71 theme downward 1155:1162 arg1 trend 1164:1168 a downward trend 1153:1168 a downward trend 1153:1168 With the increase of months, Verrucomicrobia and Akkermansia have shown a downward trend. 36082156 0 72 theme Feces 94:98 arg1 Analysis 78:85 Potential Function Analysis 59:85 Potential Function Analysis of Yak Feces before and after Weaning 59:123 Comparison of Bacterial and Fungal Community Structure and Potential Function Analysis of Yak Feces before and after Weaning. 36082156 0 72 theme Feces 94:98 arg1 Comparison 0:9 Comparison 0:9 Comparison of Bacterial and Fungal Community Structure 0:53 Comparison of Bacterial and Fungal Community Structure and Potential Function Analysis of Yak Feces before and after Weaning. 36082156 9 73 theme information 1358:1368 arg1 processes 1333:1341 cellular processes 1324:1341 cellular processes 1324:1341 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 73 theme information 1358:1368 arg1 processing 1370:1379 environmental information processing 1344:1379 environmental information processing 1344:1379 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 12 74 theme fecal 2084:2088 arg1 microflora 2090:2099 yak fecal microflora 2080:2099 yak fecal microflora 2080:2099 In general, the changes in the composition and structure of yak fecal microflora may reflect the adaptability of the intestinal microbiota. 36082156 2 75 theme feces 282:286 arg1 function 266:273 potential function 256:273 potential function 256:273 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 2 75 theme feces 282:286 arg1 structure 241:249 structure 241:249 structure 241:249 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 2 75 theme feces 282:286 arg1 diversity 230:238 microbial diversity 220:238 microbial diversity 220:238 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 7 76 dep bacteria 966:973 arg1 Firmicutes 975:984 Firmicutes 975:984 Firmicutes 975:984 The abundance and proportion of bacteria Firmicutes, Bacteroidetes, 5-7N15, and fungi Mucoromyceta changed significantly before and after weaning. 36082156 10 77 theme metabolic 1476:1484 arg1 pathways 1486:1493 secondary metabolic pathways 1466:1493 secondary metabolic pathways 1466:1493 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 7 78 theme 5-7N15 1002:1007 arg1 abundance 938:946 abundance 938:946 abundance 938:946 The abundance and proportion of bacteria Firmicutes, Bacteroidetes, 5-7N15, and fungi Mucoromyceta changed significantly before and after weaning. 36082156 7 78 theme 5-7N15 1002:1007 arg1 proportion 952:961 proportion 952:961 proportion 952:961 The abundance and proportion of bacteria Firmicutes, Bacteroidetes, 5-7N15, and fungi Mucoromyceta changed significantly before and after weaning. 36082156 9 79 theme information 1390:1400 arg1 processing 1402:1411 genetic information processing 1382:1411 genetic information processing 1382:1411 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 79 theme information 1390:1400 arg1 processes 1333:1341 cellular processes 1324:1341 cellular processes 1324:1341 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 2 80 from impact 199:204 arg1 function 266:273 potential function 256:273 potential function 256:273 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 2 80 from impact 199:204 arg1 structure 241:249 structure 241:249 structure 241:249 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 2 80 from impact 199:204 arg1 diversity 230:238 microbial diversity 220:238 microbial diversity 220:238 However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. 36082156 6 81 theme yak 899:901 arg1 feces 903:907 yak feces 899:907 yak feces of different months old 899:931 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 11 82 theme microorganisms 2004:2017 arg1 differences 1984:1994 the abundance differences 1970:1994 the abundance differences of some microorganisms 1970:2017 In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. 36082156 9 83 contain has 1296:1298 arg1 weaning 1288:1294 weaning 1288:1294 weaning 1288:1294 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 83 contain has 1296:1298 arg2 impact 1314:1319 a significant impact 1300:1319 a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems 1300:1447 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 7 84 theme Bacteroidetes 987:999 arg1 abundance 938:946 abundance 938:946 abundance 938:946 The abundance and proportion of bacteria Firmicutes, Bacteroidetes, 5-7N15, and fungi Mucoromyceta changed significantly before and after weaning. 36082156 7 84 theme Bacteroidetes 987:999 arg1 proportion 952:961 proportion 952:961 proportion 952:961 The abundance and proportion of bacteria Firmicutes, Bacteroidetes, 5-7N15, and fungi Mucoromyceta changed significantly before and after weaning. 36082156 4 85 theme high-throughput 453:467 arg1 sequencing 469:478 ITS high-throughput sequencing 449:478 ITS high-throughput sequencing 449:478 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 0 86 theme Community 35:43 arg1 Structure 45:53 Bacterial and Fungal Community Structure 14:53 Bacterial and Fungal Community Structure 14:53 Comparison of Bacterial and Fungal Community Structure and Potential Function Analysis of Yak Feces before and after Weaning. 36082156 10 87 dep xenobiotics 1720:1730 arg1 biodegradation 1732:1745 biodegradation 1732:1745 biodegradation 1732:1745 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 87 dep xenobiotics 1720:1730 arg1 xenobiotics 1720:1730 xenobiotics biodegradation and metabolism 1720:1760 xenobiotics biodegradation and metabolism 1720:1760 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 10 87 dep xenobiotics 1720:1730 arg1 metabolism 1751:1760 metabolism 1751:1760 metabolism 1751:1760 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 9 88 theme organismal 1430:1439 arg1 processes 1333:1341 cellular processes 1324:1341 cellular processes 1324:1341 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 88 theme organismal 1430:1439 arg1 systems 1441:1447 organismal systems 1430:1447 organismal systems 1430:1447 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 4 89 theme 16S 436:438 arg1 rRNA 440:443 16S rRNA 436:443 16S rRNA 436:443 Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. 36082156 3 90 theme fresh 390:394 arg1 feces 396:400 fresh feces 390:400 fresh feces 390:400 In this study, 12 Xinjiang yaks aged 3, 4, 5, and 6 months old were selected to collect fresh feces before and after weaning. 36082156 9 91 theme fecal 1210:1214 arg1 function 1226:1233 fecal microbial function 1210:1233 fecal microbial function 1210:1233 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 8 92 theme months 1102:1107 arg1 increase 1090:1097 the increase 1086:1097 the increase of months 1086:1107 With the increase of months, Verrucomicrobia and Akkermansia have shown a downward trend. 36082156 10 93 theme significant 1510:1520 arg1 impact 1522:1527 a significant impact 1508:1527 a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism 1508:1760 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 36082156 9 94 theme function 1226:1233 arg1 analysis 1198:1205 the prediction and analysis 1179:1205 analysis 1198:1205 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 9 94 theme function 1226:1233 arg1 prediction 1183:1192 the prediction and analysis 1179:1205 prediction 1183:1192 Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. 36082156 6 95 theme phylum 693:698 arg1 level 700:704 the phylum level 689:704 the phylum level 689:704 At the phylum level, Firmicutes, Bacteroidetes, Ascomycota, and Basidiomycota, and at the genus level, 5-7N15, Oscillospira, Roseburia, Dorea, Preussia, Neoascochyta, Naganishia, and Sporormiella were enriched in yak feces of different months old. 36082156 10 96 theme signal 1547:1552 arg1 transduction 1554:1565 signal transduction 1547:1565 signal transduction 1547:1565 At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. 37180436 7 0 theme AR 1458:1459 arg1 patients 1461:1468 severe AR patients 1451:1468 severe AR patients 1451:1468 The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. 37180436 1 1 theme microbiota 251:260 arg1 impact 241:246 the impact 237:246 the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) 237:318 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 11 2 theme healthy 2335:2341 arg1 controls 2343:2350 healthy controls 2335:2350 healthy controls 2335:2350 Conclusion In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. 37180436 1 3 theme allergic 265:272 arg1 AR 284:285 AR 284:285 AR 284:285 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 1 3 theme allergic 265:272 arg1 rhinitis 274:281 allergic rhinitis 265:281 allergic rhinitis (AR) 265:286 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 7 4 theme relative 1378:1385 arg1 distribution 1387:1398 The relative distribution 1374:1398 The relative distribution of Faecalibacterium 1374:1418 The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. 37180436 7 4 theme relative 1378:1385 arg1 higher 1424:1429 higher 1424:1429 higher 1424:1429 The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. 37180436 12 5 theme nAR 2462:2464 arg1 symptoms 2443:2450 symptoms 2443:2450 symptoms 2443:2450 The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. 37180436 12 5 theme nAR 2462:2464 arg1 pathogenesis 2426:2437 pathogenesis 2426:2437 pathogenesis 2426:2437 The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. 37180436 8 6 theme AR 1697:1698 arg1 microbiota 1700:1709 AR microbiota 1697:1709 AR microbiota 1697:1709 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 5 7 theme patients 999:1006 arg1 cavity 986:991 the nasal cavity 976:991 the nasal cavity of AR patients 976:1006 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 12 8 theme AR 2455:2456 arg1 symptoms 2443:2450 symptoms 2443:2450 symptoms 2443:2450 The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. 37180436 12 8 theme AR 2455:2456 arg1 pathogenesis 2426:2437 pathogenesis 2426:2437 pathogenesis 2426:2437 The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. 37180436 5 9 theme Proteobacteria 1140:1153 arg1 abundance 1083:1091 the relative abundance 1070:1091 the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli 1070:1192 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 9 theme Proteobacteria 1140:1153 arg1 lower 1198:1202 lower 1198:1202 lower 1198:1202 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 1 10 theme allergic 218:225 arg1 diseases 227:234 allergic diseases 218:234 allergic diseases 218:234 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 4 11 theme microbiota 818:827 arg1 composition 829:839 The microbiota composition 814:839 The microbiota composition of the three groups of study subjects 814:877 Results The microbiota composition of the three groups of study subjects differs significantly. 37180436 1 12 from impact 241:246 arg1 AR 284:285 AR 284:285 AR 284:285 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 1 12 from impact 241:246 arg1 rhinitis 274:281 allergic rhinitis 265:281 allergic rhinitis (AR) 265:286 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 1 12 from impact 241:246 arg1 rhinitis 305:312 non-allergic rhinitis 292:312 non-allergic rhinitis (nAR) 292:318 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 1 12 from impact 241:246 arg1 nAR 315:317 nAR 315:317 nAR 315:317 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 5 13 theme nasal 980:984 arg1 cavity 986:991 the nasal cavity 976:991 the nasal cavity of AR patients 976:1006 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 1 14 theme recent 131:136 arg1 studies 138:144 recent studies 131:144 recent studies 131:144 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 8 15 dep ICMT 1523:1526 arg1 ICMT 1576:1579 ICMT 1576:1579 ICMT 1576:1579 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 8 15 dep ICMT 1523:1526 arg1 O-methyltransferase 1556:1574 protein-S-isoprenylcysteine O-methyltransferase 1528:1574 protein-S-isoprenylcysteine O-methyltransferase 1528:1574 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 3 16 from February 516:523 arg1 patients 570:577 35 nAR patients 563:577 35 nAR patients 563:577 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 16 from February 516:523 arg1 Method 504:509 Method 504:509 Method From February to September 2022 504:541 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 16 from February 516:523 arg1 patients 550:557 35 AR patients 544:557 35 AR patients 544:557 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 16 from February 516:523 arg1 subjects 669:676 20 healthy subjects 658:676 20 healthy subjects who underwent physical examination during the same period 658:734 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 17 theme AR 547:548 arg1 Method 504:509 Method 504:509 Method From February to September 2022 504:541 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 17 theme AR 547:548 arg1 patients 550:557 35 AR patients 544:557 35 AR patients 544:557 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 2 18 from differences 390:400 arg1 role 478:481 their role 472:481 their role in the pathogenesis 472:501 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 2 18 from differences 390:400 arg1 composition 409:419 the composition 405:419 the composition of the nasal flora in patients with AR and nAR 405:466 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 10 19 theme largest 2022:2028 arg1 AUC 2030:2032 The largest AUC 2018:2032 The largest AUC for nAR 2018:2040 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 10 19 theme largest 2022:2028 arg1 0.984 2045:2049 0.984 2045:2049 0.984 2045:2049 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 2 20 with patients 443:450 arg1 AR 457:458 AR 457:458 AR 457:458 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 1 21 theme human 166:170 arg1 microbiome 172:181 the human microbiome 162:181 the human microbiome 162:181 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 3 22 theme nasal 793:797 arg1 flora 799:803 nasal flora 793:803 nasal flora 793:803 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 4 23 theme subjects 870:877 arg1 groups 854:859 the three groups 844:859 the three groups of study subjects 844:877 Results The microbiota composition of the three groups of study subjects differs significantly. 37180436 4 23 theme subjects 870:877 arg1 subjects 870:877 study subjects 864:877 study subjects 864:877 Results The microbiota composition of the three groups of study subjects differs significantly. 37180436 11 24 contain had 2275:2277 arg1 patients 2250:2257 patients 2250:2257 patients with AR and nAR 2250:2273 Conclusion In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. 37180436 11 24 contain had 2275:2277 arg2 profiles 2314:2321 significantly different microbiota profiles 2279:2321 significantly different microbiota profiles 2279:2321 Conclusion In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. 37180436 9 25 theme random 1986:1991 arg1 model 2011:2015 the constructed random forest prediction model 1970:2015 the constructed random forest prediction model 1970:2015 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 0 26 theme non-allergic 86:97 arg1 rhinitis 99:106 non-allergic rhinitis 86:106 non-allergic rhinitis 86:106 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 37180436 8 27 theme KEGG 1484:1487 arg1 annotation 1511:1520 KEGG functional enrichment annotation 1484:1520 KEGG functional enrichment annotation 1484:1520 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 9 28 theme prediction 2000:2009 arg1 model 2011:2015 the constructed random forest prediction model 1970:2015 the constructed random forest prediction model 1970:2015 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 2 29 theme study 361:365 arg1 aim 349:351 The aim 345:351 The aim of this study 345:365 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 5 30 theme Pseudomonadales 1156:1170 arg1 abundance 1083:1091 the relative abundance 1070:1091 the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli 1070:1192 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 30 theme Pseudomonadales 1156:1170 arg1 lower 1198:1202 lower 1198:1202 lower 1198:1202 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 4 31 dep Results 806:812 arg1 differs 879:885 differs 879:885 differs significantly 879:899 Results The microbiota composition of the three groups of study subjects differs significantly. 37180436 2 32 with nAR 464:466 arg1 AR 457:458 AR 457:458 AR 457:458 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 8 33 theme enrichment 1500:1509 arg1 annotation 1511:1520 KEGG functional enrichment annotation 1484:1520 KEGG functional enrichment annotation 1484:1520 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 0 34 theme Microbial 0:8 arg1 characterization 10:25 Microbial characterization 0:25 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 0:107 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 37180436 5 35 theme murinus 1110:1116 arg1 abundance 1083:1091 the relative abundance 1070:1091 the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli 1070:1192 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 35 theme murinus 1110:1116 arg1 lower 1198:1202 lower 1198:1202 lower 1198:1202 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 36 theme Lactobacillus 1119:1131 arg1 iners 1133:1137 Lactobacillus iners 1119:1137 Lactobacillus iners 1119:1137 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 2 37 theme flora 434:438 arg1 role 478:481 their role 472:481 their role in the pathogenesis 472:501 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 2 37 theme flora 434:438 arg1 composition 409:419 the composition 405:419 the composition of the nasal flora in patients with AR and nAR 405:466 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 9 38 contain had 1883:1885 arg1 model 1724:1728 the model 1720:1728 the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola 1720:1881 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 9 38 contain had 1883:1885 arg2 0.9733 1941:1946 0.9733 1941:1946 0.9733 1941:1946 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 9 38 contain had 1883:1885 arg2 area 1903:1906 the area 1899:1906 the area under the curve (AUC) 1899:1928 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 9 38 contain had 1883:1885 arg2 AUC 1925:1927 AUC 1925:1927 AUC 1925:1927 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 0 39 theme nasal 34:38 arg1 cavity 40:45 the nasal cavity 30:45 the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis 30:106 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 37180436 5 40 theme relative 1074:1081 arg1 abundance 1083:1091 the relative abundance 1070:1091 the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli 1070:1192 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 40 theme relative 1074:1081 arg1 lower 1198:1202 lower 1198:1202 lower 1198:1202 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 41 theme baumanni 964:971 arg1 higher 1026:1031 higher 1026:1031 higher 1026:1031 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 41 theme baumanni 964:971 arg1 abundance 915:923 The relative abundance 902:923 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients 902:1006 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 3 42 theme nAR 566:568 arg1 patients 570:577 35 nAR patients 563:577 35 nAR patients 563:577 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 42 theme nAR 566:568 arg1 Method 504:509 Method 504:509 Method From February to September 2022 504:541 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 8 43 from active 1687:1692 arg1 microbiota 1700:1709 AR microbiota 1697:1709 AR microbiota 1697:1709 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 12 44 theme key 2410:2412 arg1 role 2414:2417 a key role 2408:2417 a key role 2408:2417 The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. 37180436 1 45 theme diseases 227:234 arg1 pathogenesis 202:213 the pathogenesis 198:213 the pathogenesis of allergic diseases 198:234 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 11 46 theme different 2293:2301 arg1 profiles 2314:2321 significantly different microbiota profiles 2279:2321 significantly different microbiota profiles 2279:2321 Conclusion In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. 37180436 2 47 from role 478:481 arg1 nAR 464:466 nAR 464:466 nAR 464:466 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 2 47 from role 478:481 arg1 pathogenesis 490:501 the pathogenesis 486:501 the pathogenesis 486:501 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 2 47 from role 478:481 arg1 patients 443:450 patients 443:450 patients with AR 443:458 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 7 48 theme severe 1451:1456 arg1 patients 1461:1468 severe AR patients 1451:1468 severe AR patients 1451:1468 The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. 37180436 9 49 theme highest 1891:1897 arg1 0.9733 1941:1946 0.9733 1941:1946 0.9733 1941:1946 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 9 49 theme highest 1891:1897 arg1 AUC 1925:1927 AUC 1925:1927 AUC 1925:1927 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 9 49 theme highest 1891:1897 arg1 area 1903:1906 the area 1899:1906 the area under the curve (AUC) 1899:1928 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 8 50 theme AR 1588:1589 arg1 ICMT 1523:1526 ICMT 1523:1526 ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) 1523:1580 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 8 50 theme AR 1588:1589 arg1 enzyme 1611:1616 an AR microbiota-specific enzyme 1585:1616 an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota 1585:1709 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 5 51 from abundance 915:923 arg1 cavity 986:991 the nasal cavity 976:991 the nasal cavity of AR patients 976:1006 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 3 52 theme Second 619:624 arg1 Hospital 637:644 University's Second Affiliated Hospital 606:644 University's Second Affiliated Hospital 606:644 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 9 53 contain containing 1730:1739 arg2 Sutterella-SP-6FBBBBH3 1769:1790 Sutterella-SP-6FBBBBH3 1769:1790 Sutterella-SP-6FBBBBH3 1769:1790 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 9 53 contain containing 1730:1739 arg2 Parabacteroides 1741:1755 Parabacteroides 1741:1755 Parabacteroides 1741:1755 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 9 53 contain containing 1730:1739 arg2 coprocola 1873:1881 coprocola 1873:1881 coprocola 1873:1881 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 9 53 contain containing 1730:1739 arg2 luteoviolacea 1811:1823 Pseudoalteromonas luteoviolacea 1793:1823 Pseudoalteromonas luteoviolacea 1793:1823 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 9 53 contain containing 1730:1739 arg1 model 1724:1728 the model 1720:1728 the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola 1720:1881 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 9 53 contain containing 1730:1739 arg2 Lachnospiraceae 1826:1840 Lachnospiraceae 1826:1840 Lachnospiraceae 1826:1840 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 3 54 dep Medical 598:604 arg1 Hospital 637:644 University's Second Affiliated Hospital 606:644 University's Second Affiliated Hospital 606:644 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 7 55 theme Faecalibacterium 1403:1418 arg1 distribution 1387:1398 The relative distribution 1374:1398 The relative distribution of Faecalibacterium 1374:1418 The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. 37180436 7 55 theme Faecalibacterium 1403:1418 arg1 higher 1424:1429 higher 1424:1429 higher 1424:1429 The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. 37180436 10 56 contain containing 2084:2093 arg2 Lachnospiraceae 2119:2133 Lachnospiraceae 2119:2133 Lachnospiraceae 2119:2133 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 10 56 contain containing 2084:2093 arg2 Pseudomonas-SP-LTJR-52 2095:2116 Pseudomonas-SP-LTJR-52 2095:2116 Pseudomonas-SP-LTJR-52 2095:2116 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 10 56 contain containing 2084:2093 arg2 corporis 2161:2168 Prevotella corporis 2150:2168 Prevotella corporis 2150:2168 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 10 56 contain containing 2084:2093 arg2 Roseburia 2199:2207 Roseburia 2199:2207 Roseburia 2199:2207 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 10 56 contain containing 2084:2093 arg2 Anaerococcus 2171:2182 Anaerococcus 2171:2182 Anaerococcus 2171:2182 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 10 56 contain containing 2084:2093 arg1 model 2078:2082 the model 2074:2082 the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans 2074:2221 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 2 57 from composition 409:419 arg1 nAR 464:466 nAR 464:466 nAR 464:466 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 2 57 from composition 409:419 arg1 pathogenesis 490:501 the pathogenesis 486:501 the pathogenesis 486:501 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 2 57 from composition 409:419 arg1 patients 443:450 patients 443:450 patients with AR 443:458 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 2 58 from patients 443:450 arg1 role 478:481 their role 472:481 their role in the pathogenesis 472:501 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 2 58 from patients 443:450 arg1 composition 409:419 the composition 405:419 the composition of the nasal flora in patients with AR and nAR 405:466 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 3 59 dep February 516:523 arg1 to 525:526 to 525:526 to 525:526 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 59 dep February 516:523 arg1 September 528:536 September 528:536 September 528:536 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 60 theme healthy 661:667 arg1 subjects 669:676 20 healthy subjects 658:676 20 healthy subjects who underwent physical examination during the same period 658:734 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 60 theme healthy 661:667 arg1 Method 504:509 Method 504:509 Method From February to September 2022 504:541 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 4 61 theme groups 854:859 arg1 composition 829:839 The microbiota composition 814:839 The microbiota composition of the three groups of study subjects 814:877 Results The microbiota composition of the three groups of study subjects differs significantly. 37180436 10 62 theme Prevotella 2150:2159 arg1 Pseudomonas-SP-LTJR-52 2095:2116 Pseudomonas-SP-LTJR-52 2095:2116 Pseudomonas-SP-LTJR-52 2095:2116 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 10 62 theme Prevotella 2150:2159 arg1 corporis 2161:2168 Prevotella corporis 2150:2168 Prevotella corporis 2150:2168 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 2 63 from nAR 464:466 arg1 role 478:481 their role 472:481 their role in the pathogenesis 472:501 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 2 63 from nAR 464:466 arg1 composition 409:419 the composition 405:419 the composition of the nasal flora in patients with AR and nAR 405:466 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 3 64 theme physical 692:699 arg1 examination 701:711 physical examination 692:711 physical examination 692:711 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 0 65 theme allergic 64:71 arg1 rhinitis 73:80 allergic rhinitis 64:80 allergic rhinitis 64:80 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 37180436 5 66 theme AR 996:997 arg1 patients 999:1006 AR patients 996:1006 AR patients 996:1006 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 3 67 theme metagenomic 767:777 arg1 sequencing 779:788 metagenomic sequencing 767:788 metagenomic sequencing 767:788 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 68 theme same 724:727 arg1 period 729:734 the same period 720:734 the same period 720:734 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 8 69 theme functional 1489:1498 arg1 annotation 1511:1520 KEGG functional enrichment annotation 1484:1520 KEGG functional enrichment annotation 1484:1520 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 0 70 from characterization 10:25 arg1 patients 50:57 patients 50:57 patients with allergic rhinitis and non-allergic rhinitis 50:106 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 37180436 9 71 theme constructed 1974:1984 arg1 model 2011:2015 the constructed random forest prediction model 1970:2015 the constructed random forest prediction model 1970:2015 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 6 72 theme Lacttobacillus 1315:1328 arg1 kunkeei 1330:1336 Lacttobacillus kunkeei 1315:1336 Lacttobacillus kunkeei 1315:1336 In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. 37180436 3 73 theme flora 799:803 arg1 sequencing 779:788 metagenomic sequencing 767:788 metagenomic sequencing 767:788 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 3 73 theme flora 799:803 arg1 16SrDNA 755:761 16SrDNA 755:761 16SrDNA 755:761 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 4 74 theme study 864:868 arg1 subjects 870:877 study subjects 864:877 study subjects 864:877 Results The microbiota composition of the three groups of study subjects differs significantly. 37180436 0 75 from patients 50:57 arg1 characterization 10:25 Microbial characterization 0:25 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 0:107 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 37180436 9 76 theme forest 1993:1998 arg1 model 2011:2015 the constructed random forest prediction model 1970:2015 the constructed random forest prediction model 1970:2015 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 12 77 dep pathogenesis 2426:2437 arg1 the 2422:2424 the 2422:2424 the 2422:2424 The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. 37180436 5 78 theme relative 906:913 arg1 higher 1026:1031 higher 1026:1031 higher 1026:1031 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 78 theme relative 906:913 arg1 abundance 915:923 The relative abundance 902:923 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients 902:1006 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 12 79 theme AR 2516:2517 arg1 treatment 2503:2511 the treatment 2499:2511 the treatment of AR and nAR 2499:2525 The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. 37180436 0 80 from cavity 40:45 arg1 patients 50:57 patients 50:57 patients with allergic rhinitis and non-allergic rhinitis 50:106 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 37180436 12 81 theme nAR 2523:2525 arg1 treatment 2503:2511 the treatment 2499:2511 the treatment of AR and nAR 2499:2525 The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. 37180436 5 82 theme nAR 1050:1052 arg1 patients 1054:1061 nAR patients 1050:1061 nAR patients 1050:1061 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 10 83 dep Anaerococcus 2171:2182 arg1 vaginalis 2184:2192 Anaerococcus vaginalis 2171:2192 Anaerococcus vaginalis 2171:2192 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 9 84 theme Pseudoalteromonas 1793:1809 arg1 luteoviolacea 1811:1823 Pseudoalteromonas luteoviolacea 1793:1823 Pseudoalteromonas luteoviolacea 1793:1823 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 8 85 theme protein-S-isoprenylcysteine 1528:1554 arg1 ICMT 1576:1579 ICMT 1576:1579 ICMT 1576:1579 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 8 85 theme protein-S-isoprenylcysteine 1528:1554 arg1 O-methyltransferase 1556:1574 protein-S-isoprenylcysteine O-methyltransferase 1528:1574 protein-S-isoprenylcysteine O-methyltransferase 1528:1574 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 0 86 theme cavity 40:45 arg1 characterization 10:25 Microbial characterization 0:25 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 0:107 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 37180436 5 87 theme iners 1133:1137 arg1 abundance 1083:1091 the relative abundance 1070:1091 the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli 1070:1192 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 87 theme iners 1133:1137 arg1 lower 1198:1202 lower 1198:1202 lower 1198:1202 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 9 88 from 0.9733 1941:1946 arg1 model 2011:2015 the constructed random forest prediction model 1970:2015 the constructed random forest prediction model 1970:2015 For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. 37180436 2 89 theme nasal 428:432 arg1 flora 434:438 the nasal flora 424:438 the nasal flora in patients with AR and nAR 424:466 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 1 90 theme non-allergic 292:303 arg1 nAR 315:317 nAR 315:317 nAR 315:317 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 1 90 theme non-allergic 292:303 arg1 rhinitis 305:312 non-allergic rhinitis 292:312 non-allergic rhinitis (nAR) 292:318 Introduction Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. 37180436 2 91 from flora 434:438 arg1 nAR 464:466 nAR 464:466 nAR 464:466 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 2 91 from flora 434:438 arg1 patients 443:450 patients 443:450 patients with AR 443:458 The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. 37180436 11 92 dep Conclusion 2224:2233 arg1 conclusion 2238:2247 conclusion 2238:2247 conclusion 2238:2247 Conclusion In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. 37180436 3 93 theme Medical 598:604 arg1 Harbin 591:596 Harbin 591:596 Harbin Medical University's Second Affiliated Hospital 591:644 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 11 94 with patients 2250:2257 arg1 nAR 2271:2273 nAR 2271:2273 nAR 2271:2273 Conclusion In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. 37180436 11 94 with patients 2250:2257 arg1 AR 2264:2265 AR 2264:2265 AR 2264:2265 Conclusion In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. 37180436 12 95 theme nasal 2382:2386 arg1 microbiota 2388:2397 the nasal microbiota 2378:2397 the nasal microbiota 2378:2397 The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. 37180436 0 96 with patients 50:57 arg1 rhinitis 73:80 allergic rhinitis 64:80 allergic rhinitis 64:80 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 37180436 0 96 with patients 50:57 arg1 rhinitis 99:106 non-allergic rhinitis 86:106 non-allergic rhinitis 86:106 Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis. 37180436 8 97 theme glycan 1643:1648 arg1 biosynthesis 1650:1661 glycan biosynthesis 1643:1661 glycan biosynthesis 1643:1661 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 5 98 theme vulnificus 935:944 arg1 higher 1026:1031 higher 1026:1031 higher 1026:1031 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 98 theme vulnificus 935:944 arg1 abundance 915:923 The relative abundance 902:923 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients 902:1006 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 12 99 theme new 2485:2487 arg1 ideas 2489:2493 new ideas 2485:2493 new ideas for the treatment of AR and nAR 2485:2525 The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. 37180436 11 100 theme microbiota 2303:2312 arg1 profiles 2314:2321 significantly different microbiota profiles 2279:2321 significantly different microbiota profiles 2279:2321 Conclusion In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. 37180436 8 101 theme microbiota-specific 1591:1609 arg1 ICMT 1523:1526 ICMT 1523:1526 ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) 1523:1580 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 8 101 theme microbiota-specific 1591:1609 arg1 enzyme 1611:1616 an AR microbiota-specific enzyme 1585:1616 an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota 1585:1709 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 3 102 theme Affiliated 626:635 arg1 Hospital 637:644 University's Second Affiliated Hospital 606:644 University's Second Affiliated Hospital 606:644 Method From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. 37180436 8 103 from microbiota 1700:1709 arg1 active 1687:1692 active 1687:1692 active 1687:1692 According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. 37180436 10 104 dep Roseburia 2199:2207 arg1 inulinivorans 2209:2221 Roseburia inulinivorans 2199:2221 Roseburia inulinivorans 2199:2221 The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. 37180436 5 105 theme coli 1189:1192 arg1 abundance 1083:1091 the relative abundance 1070:1091 the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli 1070:1192 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37180436 5 105 theme coli 1189:1192 arg1 lower 1198:1202 lower 1198:1202 lower 1198:1202 The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. 37239822 0 0 theme Dual 95:98 arg1 Biofilms 108:115 Dual Species Biofilms 95:115 Dual Species Biofilms 95:115 Alterations in Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms. 37239822 8 1 theme correction 1746:1755 arg1 options 1757:1763 treatment correction options 1736:1763 treatment correction options for S. aureus-K 1736:1779 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 3 2 with comparison 635:644 arg1 biofilms 664:671 mono-species biofilms 651:671 mono-species biofilms of each counterpart 651:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 3 3 theme possible 705:712 arg1 mechanisms 714:723 possible mechanisms 705:723 possible mechanisms of these alterations 705:744 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 4 4 theme S. 890:891 arg1 clumps 905:910 solely S. aureus cell clumps 883:910 solely S. aureus cell clumps 883:910 In cell clumps detached from dual-species biofilms, S. aureus became insensitive to vancomycin, ampicillin, and ceftazidime compared to solely S. aureus cell clumps. 37239822 3 5 theme mono-species 651:662 arg1 biofilms 664:671 mono-species biofilms 651:671 mono-species biofilms of each counterpart 651:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 2 6 from interactions 307:318 arg1 communities 329:339 mixed communities 323:339 mixed communities 323:339 Due to intermicrobial interactions in mixed communities, bacteria change their gene expression profile, in turn leading to alterations in the biofilm structure and properties, as well as susceptibility to antimicrobials. 37239822 1 7 theme more 239:242 arg1 pathogens 244:252 rather two or even more pathogens 220:252 rather two or even more pathogens 220:252 In the last decades, it has been shown that biofilm-associated infections in most cases are caused by rather two or even more pathogens than by single microorganisms. 37239822 0 8 from Alterations 0:10 arg1 Susceptibility 26:39 Antibiotic Susceptibility 15:39 Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms 15:115 Alterations in Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms. 37239822 8 9 theme treatment 1736:1744 arg1 options 1757:1763 treatment correction options 1736:1763 treatment correction options for S. aureus-K 1736:1779 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 6 10 theme increased 1235:1243 arg1 number 1245:1250 an increased number 1232:1250 an increased number of polysaccharides 1232:1269 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 3 11 from alterations 526:536 arg1 biofilms 576:583 mixed biofilms 570:583 mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart 570:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 0 12 theme Species 100:106 arg1 Biofilms 108:115 Dual Species Biofilms 95:115 Dual Species Biofilms 95:115 Alterations in Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms. 37239822 6 13 theme differential 1189:1200 arg1 staining 1214:1221 differential fluorescent staining 1189:1221 differential fluorescent staining 1189:1221 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 4 14 theme cell 900:903 arg1 clumps 905:910 solely S. aureus cell clumps 883:910 solely S. aureus cell clumps 883:910 In cell clumps detached from dual-species biofilms, S. aureus became insensitive to vancomycin, ampicillin, and ceftazidime compared to solely S. aureus cell clumps. 37239822 6 15 theme loose 1310:1314 arg1 structure 1316:1324 more loose structure 1305:1324 more loose structure 1305:1324 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 7 16 theme mixed 1494:1498 arg1 communities 1500:1510 mixed communities 1494:1510 mixed communities 1494:1510 The qRT-PCR showed that ica operon in S. aureus became repressed in mixed communities, and polysaccharides are produced mainly by K. pneumoniae. 37239822 8 17 theme given 1708:1712 arg1 drugs 1714:1718 given drugs 1708:1718 given drugs 1708:1718 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 3 18 from pneumoniae 621:630 arg1 comparison 635:644 comparison 635:644 comparison with mono-species biofilms of each counterpart 635:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 4 19 dep S. 890:891 arg1 aureus 893:898 aureus 893:898 aureus 893:898 In cell clumps detached from dual-species biofilms, S. aureus became insensitive to vancomycin, ampicillin, and ceftazidime compared to solely S. aureus cell clumps. 37239822 3 20 theme alterations 734:744 arg1 mechanisms 714:723 possible mechanisms 705:723 possible mechanisms of these alterations 705:744 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 8 21 from knowledge 1647:1655 arg1 susceptibility 1690:1703 antibiotic susceptibility 1679:1703 antibiotic susceptibility to given drugs 1679:1718 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 8 22 theme molecular 1581:1589 arg1 trigger 1591:1597 the molecular trigger 1577:1597 the molecular trigger of these changes 1577:1614 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 5 23 theme amikacin 950:957 arg1 efficiency 936:945 the increased efficiency 922:945 the increased efficiency of amikacin and ciprofloxacin against both bacteria 922:997 In turn, the increased efficiency of amikacin and ciprofloxacin against both bacteria could be observed, compared to mono-species biofilms of each counterpart. 37239822 1 24 theme biofilm-associated 162:179 arg1 infections 181:190 biofilm-associated infections 162:190 biofilm-associated infections in most cases 162:204 In the last decades, it has been shown that biofilm-associated infections in most cases are caused by rather two or even more pathogens than by single microorganisms. 37239822 6 25 theme fluorescent 1202:1212 arg1 staining 1214:1221 differential fluorescent staining 1189:1221 differential fluorescent staining 1189:1221 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 3 26 theme efficiency 556:565 arg1 alterations 526:536 the alterations 522:536 the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart 522:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 3 27 from comparison 635:644 arg1 biofilms 576:583 mixed biofilms 570:583 mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart 570:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 2 28 theme biofilm 427:433 arg1 structure 435:443 the biofilm structure 423:443 the biofilm structure 423:443 Due to intermicrobial interactions in mixed communities, bacteria change their gene expression profile, in turn leading to alterations in the biofilm structure and properties, as well as susceptibility to antimicrobials. 37239822 8 29 theme changes 1608:1614 arg1 trigger 1591:1597 the molecular trigger 1577:1597 the molecular trigger of these changes 1577:1614 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 2 30 theme intermicrobial 292:305 arg1 interactions 307:318 intermicrobial interactions 292:318 intermicrobial interactions in mixed communities 292:339 Due to intermicrobial interactions in mixed communities, bacteria change their gene expression profile, in turn leading to alterations in the biofilm structure and properties, as well as susceptibility to antimicrobials. 37239822 2 31 theme expression 369:378 arg1 profile 380:386 their gene expression profile 358:386 their gene expression profile 358:386 Due to intermicrobial interactions in mixed communities, bacteria change their gene expression profile, in turn leading to alterations in the biofilm structure and properties, as well as susceptibility to antimicrobials. 37239822 1 32 theme single 262:267 arg1 microorganisms 269:282 single microorganisms 262:282 single microorganisms 262:282 In the last decades, it has been shown that biofilm-associated infections in most cases are caused by rather two or even more pathogens than by single microorganisms. 37239822 6 33 theme biofilm 1399:1405 arg1 permeability 1366:1377 increased permeability 1356:1377 increased permeability of the dual-species biofilm to antimicrobials 1356:1423 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 4 34 theme dual-species 776:787 arg1 biofilms 789:796 dual-species biofilms 776:796 dual-species biofilms 776:796 In cell clumps detached from dual-species biofilms, S. aureus became insensitive to vancomycin, ampicillin, and ceftazidime compared to solely S. aureus cell clumps. 37239822 3 35 from biofilms 576:583 arg1 alterations 526:536 the alterations 522:536 the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart 522:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 3 35 from biofilms 576:583 arg1 comparison 635:644 comparison 635:644 comparison with mono-species biofilms of each counterpart 635:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 1 36 theme most 195:198 arg1 cases 200:204 most cases 195:204 most cases 195:204 In the last decades, it has been shown that biofilm-associated infections in most cases are caused by rather two or even more pathogens than by single microorganisms. 37239822 0 37 theme Antibiotic 15:24 arg1 Susceptibility 26:39 Antibiotic Susceptibility 15:39 Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms 15:115 Alterations in Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms. 37239822 6 38 theme dual-species 1386:1397 arg1 biofilm 1399:1405 the dual-species biofilm 1382:1405 the dual-species biofilm 1382:1405 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 3 39 theme antimicrobials 541:554 arg1 efficiency 556:565 antimicrobials efficiency 541:565 antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart 541:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 6 40 theme Scanning 1073:1080 arg1 microscopy 1091:1100 Scanning electron microscopy 1073:1100 Scanning electron microscopy 1073:1100 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 8 41 theme S. 1769:1770 arg1 aureus-K 1772:1779 S. aureus-K 1769:1779 S. aureus-K 1769:1779 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 5 42 theme increased 926:934 arg1 efficiency 936:945 the increased efficiency 922:945 the increased efficiency of amikacin and ciprofloxacin against both bacteria 922:997 In turn, the increased efficiency of amikacin and ciprofloxacin against both bacteria could be observed, compared to mono-species biofilms of each counterpart. 37239822 8 43 from alterations 1664:1674 arg1 susceptibility 1690:1703 antibiotic susceptibility 1679:1703 antibiotic susceptibility to given drugs 1679:1718 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 6 44 theme dual-species 1163:1174 arg1 biofilm 1176:1182 the dual-species biofilm 1159:1182 the dual-species biofilm 1159:1182 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 5 45 theme mono-species 1030:1041 arg1 biofilms 1043:1050 mono-species biofilms 1030:1050 mono-species biofilms of each counterpart 1030:1070 In turn, the increased efficiency of amikacin and ciprofloxacin against both bacteria could be observed, compared to mono-species biofilms of each counterpart. 37239822 5 46 dep observed 1008:1015 arg1 compared 1018:1025 compared 1018:1025 compared to mono-species biofilms of each counterpart 1018:1070 In turn, the increased efficiency of amikacin and ciprofloxacin against both bacteria could be observed, compared to mono-species biofilms of each counterpart. 37239822 8 47 theme detailed 1638:1645 arg1 knowledge 1647:1655 detailed knowledge 1638:1655 detailed knowledge of the alterations in antibiotic susceptibility to given drugs 1638:1718 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 5 48 located observed 1008:1015 arg1 turn 916:919 turn 916:919 turn 916:919 In turn, the increased efficiency of amikacin and ciprofloxacin against both bacteria could be observed, compared to mono-species biofilms of each counterpart. 37239822 5 48 located observed 1008:1015 arg2 efficiency 936:945 the increased efficiency 922:945 the increased efficiency of amikacin and ciprofloxacin against both bacteria 922:997 In turn, the increased efficiency of amikacin and ciprofloxacin against both bacteria could be observed, compared to mono-species biofilms of each counterpart. 37239822 3 49 theme Staphylococcus 588:601 arg1 pneumoniae 621:630 Staphylococcus aureus-Klebsiella pneumoniae 588:630 Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart 588:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 2 50 from susceptibility 472:485 arg1 properties 449:458 properties 449:458 properties 449:458 Due to intermicrobial interactions in mixed communities, bacteria change their gene expression profile, in turn leading to alterations in the biofilm structure and properties, as well as susceptibility to antimicrobials. 37239822 2 50 from susceptibility 472:485 arg1 structure 435:443 the biofilm structure 423:443 the biofilm structure 423:443 Due to intermicrobial interactions in mixed communities, bacteria change their gene expression profile, in turn leading to alterations in the biofilm structure and properties, as well as susceptibility to antimicrobials. 37239822 3 51 theme mixed 570:574 arg1 biofilms 576:583 mixed biofilms 570:583 mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart 570:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 6 52 theme biofilm 1176:1182 arg1 structure 1146:1154 the porous structure 1135:1154 the porous structure of the dual-species biofilm 1135:1182 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 0 53 theme aureus 59:64 arg1 Susceptibility 26:39 Antibiotic Susceptibility 15:39 Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms 15:115 Alterations in Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms. 37239822 6 54 theme increased 1356:1364 arg1 permeability 1366:1377 increased permeability 1356:1377 increased permeability of the dual-species biofilm to antimicrobials 1356:1423 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 5 55 theme counterpart 1060:1070 arg1 biofilms 1043:1050 mono-species biofilms 1030:1050 mono-species biofilms of each counterpart 1030:1070 In turn, the increased efficiency of amikacin and ciprofloxacin against both bacteria could be observed, compared to mono-species biofilms of each counterpart. 37239822 1 56 theme last 125:128 arg1 decades 130:136 the last decades 121:136 the last decades 121:136 In the last decades, it has been shown that biofilm-associated infections in most cases are caused by rather two or even more pathogens than by single microorganisms. 37239822 7 57 from operon 1454:1459 arg1 aureus 1467:1472 S. aureus 1464:1472 S. aureus 1464:1472 The qRT-PCR showed that ica operon in S. aureus became repressed in mixed communities, and polysaccharides are produced mainly by K. pneumoniae. 37239822 7 58 theme ica 1450:1452 arg1 operon 1454:1459 ica operon 1450:1459 ica operon in S. aureus 1450:1472 The qRT-PCR showed that ica operon in S. aureus became repressed in mixed communities, and polysaccharides are produced mainly by K. pneumoniae. 37239822 2 59 theme mixed 323:327 arg1 communities 329:339 mixed communities 323:339 mixed communities 323:339 Due to intermicrobial interactions in mixed communities, bacteria change their gene expression profile, in turn leading to alterations in the biofilm structure and properties, as well as susceptibility to antimicrobials. 37239822 5 60 theme ciprofloxacin 963:975 arg1 efficiency 936:945 the increased efficiency 922:945 the increased efficiency of amikacin and ciprofloxacin against both bacteria 922:997 In turn, the increased efficiency of amikacin and ciprofloxacin against both bacteria could be observed, compared to mono-species biofilms of each counterpart. 37239822 8 61 theme alterations 1664:1674 arg1 knowledge 1647:1655 detailed knowledge 1638:1655 detailed knowledge of the alterations in antibiotic susceptibility to given drugs 1638:1718 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 8 62 from susceptibility 1690:1703 arg1 knowledge 1647:1655 detailed knowledge 1638:1655 detailed knowledge of the alterations in antibiotic susceptibility to given drugs 1638:1718 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 7 63 theme K. 1556:1557 arg1 pneumoniae 1559:1568 K. pneumoniae 1556:1568 K. pneumoniae 1556:1568 The qRT-PCR showed that ica operon in S. aureus became repressed in mixed communities, and polysaccharides are produced mainly by K. pneumoniae. 37239822 6 64 theme polysaccharides 1255:1269 arg1 number 1245:1250 an increased number 1232:1250 an increased number of polysaccharides 1232:1269 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 1 65 from infections 181:190 arg1 cases 200:204 most cases 195:204 most cases 195:204 In the last decades, it has been shown that biofilm-associated infections in most cases are caused by rather two or even more pathogens than by single microorganisms. 37239822 3 66 from efficiency 556:565 arg1 biofilms 576:583 mixed biofilms 570:583 mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart 570:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 4 67 theme cell 750:753 arg1 clumps 755:760 cell clumps 750:760 cell clumps detached from dual-species biofilms 750:796 In cell clumps detached from dual-species biofilms, S. aureus became insensitive to vancomycin, ampicillin, and ceftazidime compared to solely S. aureus cell clumps. 37239822 0 68 theme pneumoniae 81:90 arg1 Susceptibility 26:39 Antibiotic Susceptibility 15:39 Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms 15:115 Alterations in Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms. 37239822 3 69 theme counterpart 681:691 arg1 biofilms 664:671 mono-species biofilms 651:671 mono-species biofilms of each counterpart 651:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 3 70 theme aureus-Klebsiella 603:619 arg1 pneumoniae 621:630 Staphylococcus aureus-Klebsiella pneumoniae 588:630 Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart 588:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 6 71 theme electron 1082:1089 arg1 microscopy 1091:1100 Scanning electron microscopy 1073:1100 Scanning electron microscopy 1073:1100 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 2 72 theme gene 364:367 arg1 profile 380:386 their gene expression profile 358:386 their gene expression profile 358:386 Due to intermicrobial interactions in mixed communities, bacteria change their gene expression profile, in turn leading to alterations in the biofilm structure and properties, as well as susceptibility to antimicrobials. 37239822 6 73 theme confocal 1106:1113 arg1 microscopy 1115:1124 confocal microscopy 1106:1124 confocal microscopy 1106:1124 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 8 74 theme antibiotic 1679:1688 arg1 susceptibility 1690:1703 antibiotic susceptibility 1679:1703 antibiotic susceptibility to given drugs 1679:1718 While the molecular trigger of these changes remains undiscovered, detailed knowledge of the alterations in antibiotic susceptibility to given drugs opens doors for treatment correction options for S. aureus-K. 37239822 6 75 dep turn 1289:1292 arg1 leading 1294:1300 leading 1294:1300 leading to more loose structure 1294:1324 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 6 75 dep turn 1289:1292 arg1 providing 1346:1354 providing 1346:1354 thus apparently providing increased permeability of the dual-species biofilm to antimicrobials 1330:1423 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37239822 0 76 from Susceptibility 26:39 arg1 Biofilms 108:115 Dual Species Biofilms 95:115 Dual Species Biofilms 95:115 Alterations in Antibiotic Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae in Dual Species Biofilms. 37239822 3 77 theme pneumoniae 621:630 arg1 biofilms 576:583 mixed biofilms 570:583 mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart 570:691 Here, we report the alterations of antimicrobials efficiency in mixed biofilms of Staphylococcus aureus-Klebsiella pneumoniae in comparison with mono-species biofilms of each counterpart and discuss possible mechanisms of these alterations. 37239822 2 78 from alterations 408:418 arg1 properties 449:458 properties 449:458 properties 449:458 Due to intermicrobial interactions in mixed communities, bacteria change their gene expression profile, in turn leading to alterations in the biofilm structure and properties, as well as susceptibility to antimicrobials. 37239822 2 78 from alterations 408:418 arg1 structure 435:443 the biofilm structure 423:443 the biofilm structure 423:443 Due to intermicrobial interactions in mixed communities, bacteria change their gene expression profile, in turn leading to alterations in the biofilm structure and properties, as well as susceptibility to antimicrobials. 37239822 6 79 theme porous 1139:1144 arg1 structure 1146:1154 the porous structure 1135:1154 the porous structure of the dual-species biofilm 1135:1182 Scanning electron microscopy and confocal microscopy indicate the porous structure of the dual-species biofilm, and differential fluorescent staining revealed an increased number of polysaccharides in the matrix, in turn leading to more loose structure and thus apparently providing increased permeability of the dual-species biofilm to antimicrobials. 37001571 17 0 theme human 2235:2239 arg1 diseases 2241:2248 human diseases 2235:2248 human diseases 2235:2248 The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. 37001571 15 1 theme OTUs 1749:1752 arg1 percentage 1728:1737 The percentage 1724:1737 The percentage of common OTUs 1724:1752 The percentage of common OTUs was 41.2%. 37001571 15 1 theme OTUs 1749:1752 arg1 % 1762:1762 41.2% 1758:1762 41.2% 1758:1762 The percentage of common OTUs was 41.2%. 37001571 3 2 theme rats 501:504 arg1 GM 460:461 GM 460:461 GM 460:461 This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. 37001571 3 2 theme rats 501:504 arg1 microbiota 448:457 the gut microbiota 440:457 the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats 440:504 This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. 37001571 9 3 from OTUs 1138:1141 arg1 groups 1195:1200 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1146:1200 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1146:1200 A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. 37001571 19 4 dep composition 2557:2567 arg1 the 2542:2544 the 2542:2544 the 2542:2544 DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis. 37001571 14 5 theme operational 1615:1625 arg1 OTUs 1644:1647 OTUs 1644:1647 OTUs 1644:1647 Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. 37001571 14 5 theme operational 1615:1625 arg1 units 1637:1641 1235 operational taxonomic units 1610:1641 1235 operational taxonomic units (OTUs) 1610:1648 Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. 37001571 17 6 theme genetic 2267:2273 arg1 processing 2287:2296 genetic information processing 2267:2296 genetic information processing 2267:2296 The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. 37001571 18 7 theme GM 2338:2339 arg1 homeostasis 2341:2351 GM homeostasis 2338:2351 GM homeostasis 2338:2351 Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. 37001571 19 8 theme bone 2518:2521 arg1 loss 2523:2526 bone loss 2518:2526 bone loss 2518:2526 DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis. 37001571 0 9 theme gut 54:56 arg1 microbiota 58:67 gut microbiota 54:67 gut microbiota 54:67 Diosgenin reduces bone loss through the regulation of gut microbiota in ovariectomized rats. 37001571 9 10 theme OVX + DIO 1185:1193 arg1 groups 1195:1200 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1146:1200 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1146:1200 A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. 37001571 6 11 theme GM 939:940 arg1 function 927:934 function 927:934 function 927:934 Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. 37001571 6 11 theme GM 939:940 arg1 structure 913:921 structure 913:921 structure 913:921 Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. 37001571 6 12 dep structure 913:921 arg1 the 909:911 the 909:911 the 909:911 Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. 37001571 1 13 dep Trigonella 211:220 arg1 graecum 229:235 Trigonella foenum graecum 211:235 Trigonella foenum graecum 211:235 Diosgenin (DIO) is an aglycone of steroid saponins acquired from plants, including Dioscorea alata, Smilax China, and Trigonella foenum graecum, acting as an anti-osteoporosis, anti-diabetic, anti-hyperlipidemic, anti-inflammatory. 37001571 1 14 theme saponins 135:142 arg1 Diosgenin 93:101 Diosgenin 93:101 Diosgenin (DIO) 93:107 Diosgenin (DIO) is an aglycone of steroid saponins acquired from plants, including Dioscorea alata, Smilax China, and Trigonella foenum graecum, acting as an anti-osteoporosis, anti-diabetic, anti-hyperlipidemic, anti-inflammatory. 37001571 1 14 theme saponins 135:142 arg1 aglycone 115:122 an aglycone 112:122 an aglycone 112:122 Diosgenin (DIO) is an aglycone of steroid saponins acquired from plants, including Dioscorea alata, Smilax China, and Trigonella foenum graecum, acting as an anti-osteoporosis, anti-diabetic, anti-hyperlipidemic, anti-inflammatory. 37001571 16 15 with Treatment 1765:1773 arg1 DIO 1780:1782 DIO 1780:1782 DIO 1780:1782 Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens. 37001571 17 16 theme DIO 2128:2130 arg1 effect 2118:2123 The anti-osteoporosis effect 2096:2123 The anti-osteoporosis effect of DIO 2096:2130 The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. 37001571 14 17 theme Metagenomics 1551:1562 arg1 results 1575:1581 Metagenomics sequencing results 1551:1581 Metagenomics sequencing results 1551:1581 Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. 37001571 13 18 theme structural 1514:1523 arg1 parameters 1525:1534 structural parameters 1514:1534 structural parameters 1514:1534 DIO treatment improved the bone microstructure and structural parameters of rat tibias. 37001571 0 19 from regulation 40:49 arg1 rats 87:90 ovariectomized rats 72:90 ovariectomized rats 72:90 Diosgenin reduces bone loss through the regulation of gut microbiota in ovariectomized rats. 37001571 19 20 theme novel 2591:2595 arg1 strategy 2597:2604 a novel strategy 2589:2604 a novel strategy for preventing osteoporosis 2589:2632 DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis. 37001571 19 20 theme novel 2591:2595 arg1 composition 2557:2567 composition 2557:2567 composition 2557:2567 DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis. 37001571 1 21 dep anti-diabetic 270:282 arg1 anti-inflammatory 306:322 anti-inflammatory 306:322 anti-inflammatory 306:322 Diosgenin (DIO) is an aglycone of steroid saponins acquired from plants, including Dioscorea alata, Smilax China, and Trigonella foenum graecum, acting as an anti-osteoporosis, anti-diabetic, anti-hyperlipidemic, anti-inflammatory. 37001571 1 21 dep anti-diabetic 270:282 arg1 anti-hyperlipidemic 285:303 anti-hyperlipidemic 285:303 anti-hyperlipidemic 285:303 Diosgenin (DIO) is an aglycone of steroid saponins acquired from plants, including Dioscorea alata, Smilax China, and Trigonella foenum graecum, acting as an anti-osteoporosis, anti-diabetic, anti-hyperlipidemic, anti-inflammatory. 37001571 17 22 theme information 2171:2181 arg1 processing 2183:2192 environmental information processing 2157:2192 environmental information processing 2157:2192 The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. 37001571 0 23 theme bone 18:21 arg1 loss 23:26 bone loss 18:26 bone loss 18:26 Diosgenin reduces bone loss through the regulation of gut microbiota in ovariectomized rats. 37001571 8 24 theme taxonomic 1008:1016 arg1 OTUs 1025:1028 OTUs 1025:1028 OTUs 1025:1028 Operational taxonomic units (OTUs) were clustered in the filtered reads. 37001571 8 24 theme taxonomic 1008:1016 arg1 units 1018:1022 Operational taxonomic units 996:1022 Operational taxonomic units (OTUs) 996:1029 Operational taxonomic units (OTUs) were clustered in the filtered reads. 37001571 12 25 theme OVX-induced 1403:1413 arg1 gain 1422:1425 OVX-induced weight gain 1403:1425 OVX-induced weight gain 1403:1425 After a 12-week treatment, DIO administration prevented OVX-induced weight gain and increased the estradiol levels. 37001571 16 26 theme Romboutsia_idealis 1904:1921 arg1 abundance 1845:1853 the abundance 1841:1853 the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis 1841:1921 Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens. 37001571 4 27 theme Sprague-Dawley 514:527 arg1 rats 529:532 Female Sprague-Dawley rats 507:532 Female Sprague-Dawley rats 507:532 Female Sprague-Dawley rats were randomly divided into sham operation (sham + vehicle group) or ovariectomy. 37001571 18 28 theme amino 2406:2410 arg1 acids 2412:2416 other amino acids 2400:2416 other amino acids 2400:2416 Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. 37001571 6 29 theme micro-CT 787:794 arg1 scanning 796:803 micro-CT scanning 787:803 micro-CT scanning 787:803 Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. 37001571 13 30 theme rat 1539:1541 arg1 tibias 1543:1548 rat tibias 1539:1548 rat tibias 1539:1548 DIO treatment improved the bone microstructure and structural parameters of rat tibias. 37001571 10 31 theme specific 1248:1255 arg1 GM 1257:1258 the specific GM 1244:1258 the specific GM of the three groups 1244:1278 LEfSe analysis was conducted to evaluate the specific GM of the three groups. 37001571 2 32 theme Recent 325:330 arg1 studies 332:338 Recent studies 325:338 Recent studies 325:338 Recent studies have demonstrated that DIO reduces bone loss. 37001571 18 33 theme glycans 2423:2429 arg1 metabolism 2371:2380 the metabolism 2367:2380 the metabolism of carbohydrates, other amino acids, and glycans 2367:2429 Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. 37001571 3 34 theme gut 444:446 arg1 GM 460:461 GM 460:461 GM 460:461 This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. 37001571 3 34 theme gut 444:446 arg1 microbiota 448:457 the gut microbiota 440:457 the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats 440:504 This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. 37001571 14 35 theme OVX + vehicle 1673:1685 arg1 groups 1702:1707 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1653:1707 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1653:1707 Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. 37001571 6 36 theme serum 763:767 arg1 levels 779:784 serum estradiol levels 763:784 serum estradiol levels 763:784 Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. 37001571 4 37 theme sham 561:564 arg1 operation 566:574 sham operation 561:574 sham operation (sham + vehicle group) 561:597 Female Sprague-Dawley rats were randomly divided into sham operation (sham + vehicle group) or ovariectomy. 37001571 4 37 theme sham 561:564 arg1 group 592:596 sham + vehicle group 577:596 sham + vehicle group 577:596 Female Sprague-Dawley rats were randomly divided into sham operation (sham + vehicle group) or ovariectomy. 37001571 11 38 theme GM 1285:1286 arg1 functions 1288:1296 The GM functions 1281:1296 The GM functions 1281:1296 The GM functions were analyzed using the KEGG and CAZy databases. 37001571 9 39 theme Venn 1071:1074 arg1 analysis 1084:1091 A Venn diagram analysis 1069:1091 A Venn diagram analysis 1069:1091 A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. 37001571 3 40 theme ovariectomized 467:480 arg1 rats 501:504 ovariectomized (OVX) osteoporotic rats 467:504 ovariectomized (OVX) osteoporotic rats 467:504 This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. 37001571 14 41 theme sham + vehicle 1657:1670 arg1 groups 1702:1707 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1653:1707 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1653:1707 Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. 37001571 13 42 dep microstructure 1495:1508 arg1 the 1486:1488 the 1486:1488 the 1486:1488 DIO treatment improved the bone microstructure and structural parameters of rat tibias. 37001571 1 43 theme anti-diabetic 270:282 arg1 anti-osteoporosis 251:267 an anti-osteoporosis 248:267 an anti-osteoporosis 248:267 Diosgenin (DIO) is an aglycone of steroid saponins acquired from plants, including Dioscorea alata, Smilax China, and Trigonella foenum graecum, acting as an anti-osteoporosis, anti-diabetic, anti-hyperlipidemic, anti-inflammatory. 37001571 5 44 theme OVX + DIO 698:706 arg1 DIO 693:695 DIO 693:695 DIO (OVX + DIO group) 693:713 For 12 weeks, OVX rats were treated using a vehicle (OVX + vehicle group) and DIO (OVX + DIO group). 37001571 5 44 theme OVX + DIO 698:706 arg1 group 708:712 OVX + DIO group 698:712 OVX + DIO group 698:712 For 12 weeks, OVX rats were treated using a vehicle (OVX + vehicle group) and DIO (OVX + DIO group). 37001571 3 45 from effects 422:428 arg1 GM 460:461 GM 460:461 GM 460:461 This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. 37001571 3 45 from effects 422:428 arg1 microbiota 448:457 the gut microbiota 440:457 the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats 440:504 This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. 37001571 17 46 theme organismal 2195:2204 arg1 Systems 2206:2212 organismal Systems 2195:2212 organismal Systems 2195:2212 The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. 37001571 12 47 theme 12-week 1355:1361 arg1 treatment 1363:1371 a 12-week treatment 1353:1371 a 12-week treatment 1353:1371 After a 12-week treatment, DIO administration prevented OVX-induced weight gain and increased the estradiol levels. 37001571 15 48 theme common 1742:1747 arg1 OTUs 1749:1752 common OTUs 1742:1752 common OTUs 1742:1752 The percentage of common OTUs was 41.2%. 37001571 3 49 theme osteoporotic 488:499 arg1 rats 501:504 ovariectomized (OVX) osteoporotic rats 467:504 ovariectomized (OVX) osteoporotic rats 467:504 This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. 37001571 6 50 theme bone 831:834 arg1 quality 836:842 bone quality 831:842 bone quality 831:842 Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. 37001571 9 51 theme common 1120:1125 arg1 OTUs 1138:1141 the common and unique OTUs 1116:1141 the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1116:1200 A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. 37001571 18 52 theme carbohydrates 2385:2397 arg1 metabolism 2371:2380 the metabolism 2367:2380 the metabolism of carbohydrates, other amino acids, and glycans 2367:2429 Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. 37001571 9 53 theme unique 1131:1136 arg1 OTUs 1138:1141 the common and unique OTUs 1116:1141 the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1116:1200 A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. 37001571 13 54 theme bone 1490:1493 arg1 microstructure 1495:1508 bone microstructure 1490:1508 bone microstructure 1490:1508 DIO treatment improved the bone microstructure and structural parameters of rat tibias. 37001571 7 55 theme chimera 977:983 arg1 sequences 985:993 chimera sequences 977:993 chimera sequences 977:993 Raw reads were filtered to remove chimera sequences. 37001571 14 56 theme taxonomic 1627:1635 arg1 OTUs 1644:1647 OTUs 1644:1647 OTUs 1644:1647 Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. 37001571 14 56 theme taxonomic 1627:1635 arg1 units 1637:1641 1235 operational taxonomic units 1610:1641 1235 operational taxonomic units (OTUs) 1610:1648 Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. 37001571 16 57 theme GM 1812:1813 arg1 composition 1797:1807 the composition 1793:1807 the composition of GM in OVX rats 1793:1825 Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens. 37001571 6 58 theme metagenomics 874:885 arg1 sequencing 887:896 metagenomics sequencing 874:896 metagenomics sequencing 874:896 Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. 37001571 5 59 theme OVX 629:631 arg1 rats 633:636 OVX rats 629:636 OVX rats 629:636 For 12 weeks, OVX rats were treated using a vehicle (OVX + vehicle group) and DIO (OVX + DIO group). 37001571 9 60 theme sham + vehicle 1150:1163 arg1 groups 1195:1200 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1146:1200 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1146:1200 A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. 37001571 13 61 theme DIO 1463:1465 arg1 treatment 1467:1475 DIO treatment 1463:1475 DIO treatment 1463:1475 DIO treatment improved the bone microstructure and structural parameters of rat tibias. 37001571 19 62 theme structural 2546:2555 arg1 composition 2557:2567 composition 2557:2567 composition 2557:2567 DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis. 37001571 19 62 theme structural 2546:2555 arg1 strategy 2597:2604 a novel strategy 2589:2604 a novel strategy for preventing osteoporosis 2589:2632 DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis. 37001571 9 63 theme OVX + vehicle 1166:1178 arg1 groups 1195:1200 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1146:1200 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1146:1200 A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. 37001571 17 64 theme information 2275:2285 arg1 processing 2287:2296 genetic information processing 2267:2296 genetic information processing 2267:2296 The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. 37001571 0 65 theme microbiota 58:67 arg1 regulation 40:49 the regulation 36:49 the regulation of gut microbiota in ovariectomized rats 36:90 Diosgenin reduces bone loss through the regulation of gut microbiota in ovariectomized rats. 37001571 0 66 theme ovariectomized 72:85 arg1 rats 87:90 ovariectomized rats 72:90 ovariectomized rats 72:90 Diosgenin reduces bone loss through the regulation of gut microbiota in ovariectomized rats. 37001571 1 67 theme steroid 127:133 arg1 saponins 135:142 steroid saponins 127:142 steroid saponins acquired from plants, including Dioscorea alata, Smilax China, and Trigonella foenum graecum 127:235 Diosgenin (DIO) is an aglycone of steroid saponins acquired from plants, including Dioscorea alata, Smilax China, and Trigonella foenum graecum, acting as an anti-osteoporosis, anti-diabetic, anti-hyperlipidemic, anti-inflammatory. 37001571 19 68 theme GM 2585:2586 arg1 composition 2557:2567 composition 2557:2567 composition 2557:2567 DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis. 37001571 19 68 theme GM 2585:2586 arg1 strategy 2597:2604 a novel strategy 2589:2604 a novel strategy for preventing osteoporosis 2589:2632 DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis. 37001571 19 68 theme GM 2585:2586 arg1 function 2573:2580 function 2573:2580 function 2573:2580 DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis. 37001571 18 69 theme energy 2457:2462 arg1 metabolism 2464:2473 energy metabolism 2457:2473 energy metabolism 2457:2473 Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. 37001571 5 70 theme OVX + vehicle 668:680 arg1 vehicle 659:665 a vehicle 657:665 a vehicle (OVX + vehicle group) 657:687 For 12 weeks, OVX rats were treated using a vehicle (OVX + vehicle group) and DIO (OVX + DIO group). 37001571 5 70 theme OVX + vehicle 668:680 arg1 group 682:686 OVX + vehicle group 668:686 OVX + vehicle group 668:686 For 12 weeks, OVX rats were treated using a vehicle (OVX + vehicle group) and DIO (OVX + DIO group). 37001571 14 71 theme sequencing 1564:1573 arg1 results 1575:1581 Metagenomics sequencing results 1551:1581 Metagenomics sequencing results 1551:1581 Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. 37001571 16 72 theme Adlercreutzia 1873:1885 arg1 abundance 1845:1853 the abundance 1841:1853 the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis 1841:1921 Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens. 37001571 12 73 theme estradiol 1445:1453 arg1 levels 1455:1460 the estradiol levels 1441:1460 the estradiol levels 1441:1460 After a 12-week treatment, DIO administration prevented OVX-induced weight gain and increased the estradiol levels. 37001571 17 74 theme Cellular 2215:2222 arg1 Processes 2224:2232 Cellular Processes 2215:2232 Cellular Processes 2215:2232 The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. 37001571 10 75 theme LEfSe 1203:1207 arg1 analysis 1209:1216 LEfSe analysis 1203:1216 LEfSe analysis 1203:1216 LEfSe analysis was conducted to evaluate the specific GM of the three groups. 37001571 11 76 theme CAZy 1331:1334 arg1 databases 1336:1344 the KEGG and CAZy databases 1318:1344 the KEGG and CAZy databases 1318:1344 The GM functions were analyzed using the KEGG and CAZy databases. 37001571 16 77 theme Romboutsia 1888:1897 arg1 abundance 1845:1853 the abundance 1841:1853 the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis 1841:1921 Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens. 37001571 18 78 theme nucleotide 2480:2489 arg1 metabolism 2491:2500 nucleotide metabolism 2480:2500 nucleotide metabolism 2480:2500 Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. 37001571 7 79 dep Raw 943:945 arg1 reads 947:951 reads 947:951 reads 947:951 Raw reads were filtered to remove chimera sequences. 37001571 2 80 theme bone 375:378 arg1 loss 380:383 bone loss 375:383 bone loss 375:383 Recent studies have demonstrated that DIO reduces bone loss. 37001571 8 81 theme Operational 996:1006 arg1 OTUs 1025:1028 OTUs 1025:1028 OTUs 1025:1028 Operational taxonomic units (OTUs) were clustered in the filtered reads. 37001571 8 81 theme Operational 996:1006 arg1 units 1018:1022 Operational taxonomic units 996:1022 Operational taxonomic units (OTUs) 996:1029 Operational taxonomic units (OTUs) were clustered in the filtered reads. 37001571 4 82 theme Female 507:512 arg1 rats 529:532 Female Sprague-Dawley rats 507:532 Female Sprague-Dawley rats 507:532 Female Sprague-Dawley rats were randomly divided into sham operation (sham + vehicle group) or ovariectomy. 37001571 8 83 dep the 1049:1051 arg1 reads 1062:1066 reads 1062:1066 reads 1062:1066 Operational taxonomic units (OTUs) were clustered in the filtered reads. 37001571 17 84 theme environmental 2157:2169 arg1 processing 2183:2192 environmental information processing 2157:2192 environmental information processing 2157:2192 The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. 37001571 3 85 dep ovariectomized 467:480 arg1 OVX 483:485 OVX 483:485 OVX 483:485 This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. 37001571 18 86 with treatment 2310:2318 arg1 DIO 2325:2327 DIO 2325:2327 DIO 2325:2327 Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. 37001571 18 87 theme acids 2412:2416 arg1 metabolism 2371:2380 the metabolism 2367:2380 the metabolism of carbohydrates, other amino acids, and glycans 2367:2429 Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. 37001571 16 88 theme OVX 1818:1820 arg1 rats 1822:1825 OVX rats 1818:1825 OVX rats 1818:1825 Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens. 37001571 18 89 theme other 2400:2404 arg1 acids 2412:2416 other amino acids 2400:2416 other amino acids 2400:2416 Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. 37001571 3 90 theme DIO 433:435 arg1 effects 422:428 the effects 418:428 the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats 418:504 This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. 37001571 14 91 theme OVX + DIO 1692:1700 arg1 groups 1702:1707 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1653:1707 the sham + vehicle, OVX + vehicle, and OVX + DIO groups 1653:1707 Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. 37001571 12 92 theme weight 1415:1420 arg1 gain 1422:1425 OVX-induced weight gain 1403:1425 OVX-induced weight gain 1403:1425 After a 12-week treatment, DIO administration prevented OVX-induced weight gain and increased the estradiol levels. 37001571 13 93 theme tibias 1543:1548 arg1 microstructure 1495:1508 bone microstructure 1490:1508 bone microstructure 1490:1508 DIO treatment improved the bone microstructure and structural parameters of rat tibias. 37001571 13 93 theme tibias 1543:1548 arg1 parameters 1525:1534 structural parameters 1514:1534 structural parameters 1514:1534 DIO treatment improved the bone microstructure and structural parameters of rat tibias. 37001571 6 94 theme estradiol 769:777 arg1 levels 779:784 serum estradiol levels 763:784 serum estradiol levels 763:784 Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. 37001571 9 95 theme diagram 1076:1082 arg1 analysis 1084:1091 A Venn diagram analysis 1069:1091 A Venn diagram analysis 1069:1091 A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. 37001571 16 96 theme Gammaproteobacteria 1973:1991 arg1 abundance 1940:1948 the abundance 1936:1948 the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens 1936:2093 Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens. 37001571 17 97 theme anti-osteoporosis 2100:2116 arg1 effect 2118:2123 The anti-osteoporosis effect 2096:2123 The anti-osteoporosis effect of DIO 2096:2130 The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. 37001571 10 98 theme groups 1273:1278 arg1 GM 1257:1258 the specific GM 1244:1258 the specific GM of the three groups 1244:1278 LEfSe analysis was conducted to evaluate the specific GM of the three groups. 37001571 11 99 theme KEGG 1322:1325 arg1 databases 1336:1344 the KEGG and CAZy databases 1318:1344 the KEGG and CAZy databases 1318:1344 The GM functions were analyzed using the KEGG and CAZy databases. 37001571 12 100 theme DIO 1374:1376 arg1 administration 1378:1391 DIO administration 1374:1391 DIO administration 1374:1391 After a 12-week treatment, DIO administration prevented OVX-induced weight gain and increased the estradiol levels. 37001571 4 101 theme sham + vehicle 577:590 arg1 operation 566:574 sham operation 561:574 sham operation (sham + vehicle group) 561:597 Female Sprague-Dawley rats were randomly divided into sham operation (sham + vehicle group) or ovariectomy. 37001571 4 101 theme sham + vehicle 577:590 arg1 group 592:596 sham + vehicle group 577:596 sham + vehicle group 577:596 Female Sprague-Dawley rats were randomly divided into sham operation (sham + vehicle group) or ovariectomy. 37001571 16 102 from composition 1797:1807 arg1 rats 1822:1825 OVX rats 1818:1825 OVX rats 1818:1825 Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens. 36424788 7 0 dep elevated 953:960 arg1 p<0.001 963:969 p<0.001 963:969 p<0.001 963:969 RESULTS The UA level in the hyperuricemia group was significantly elevated (p<0.001), suggesting that the model was successfully established. 36424788 11 1 theme relative 1520:1527 arg1 abundance 1529:1537 the relative abundance 1516:1537 the relative abundance of Lactobacillus 1516:1554 Berberine treatment reduced the relative abundance of Bacteroidetes, and increased the relative abundance of Lactobacillus. 36424788 13 2 theme UA 1818:1819 arg1 metabolism 1821:1830 UA metabolism 1818:1830 UA metabolism 1818:1830 CONCLUSION Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota. 36424788 1 3 theme multifunctional 171:185 arg1 nature 187:192 the multifunctional nature 167:192 the multifunctional nature of berberine 167:205 BACKGROUND Intestinal microbiota is the primary target for the multifunctional nature of berberine. 36424788 10 4 theme microbiota 1373:1382 arg1 composition 1384:1394 gut microbiota composition 1369:1394 gut microbiota composition 1369:1394 Further 16S sequencing revealed that berberine affected the gut microbiota composition and diversity in hyperuricemia rats. 36424788 8 5 theme blood 1071:1075 arg1 levels 1061:1066 levels 1061:1066 levels of blood and fecal UA 1061:1088 After treatment with berberine, levels of blood and fecal UA significantly decreased (p<0.001), but not uric UA. 36424788 12 6 theme multiple 1609:1616 arg1 N-glycans 1705:1713 N-glycans 1705:1713 N-glycans 1705:1713 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 12 6 theme multiple 1609:1616 arg1 metabolism 1690:1699 starch and sucrose metabolism 1671:1699 metabolism 1690:1699 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 12 6 theme multiple 1609:1616 arg1 metabolism 1659:1668 sphingolipid metabolism 1646:1668 sphingolipid metabolism 1646:1668 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 12 6 theme multiple 1609:1616 arg1 pathways 1628:1635 multiple metabolic pathways 1609:1635 multiple metabolic pathways 1609:1635 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 4 7 theme = 593:593 arg1 n 591:591 n = 12 591:596 n = 12 591:596 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 4 7 theme = 593:593 arg1 group 584:588 a hyperuricemia group 568:588 a hyperuricemia group (n = 12) 568:597 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 8 8 theme fecal 1081:1085 arg1 UA 1087:1088 fecal UA 1081:1088 fecal UA 1081:1088 After treatment with berberine, levels of blood and fecal UA significantly decreased (p<0.001), but not uric UA. 36424788 6 9 theme gut 827:829 arg1 microbiota 831:840 gut microbiota 827:840 gut microbiota 827:840 The alterations in gut microbiota were investigated using 16S rRNA sequencing. 36424788 0 10 from Flora 73:77 arg1 Rats 96:99 Hyperuricemia Rats 82:99 Hyperuricemia Rats Model 82:105 Berberine Regulates the Metabolism of Uric Acid and Modulates Intestinal Flora in Hyperuricemia Rats Model. 36424788 8 11 theme uric 1133:1136 arg1 UA 1138:1139 uric UA 1133:1139 uric UA 1133:1139 After treatment with berberine, levels of blood and fecal UA significantly decreased (p<0.001), but not uric UA. 36424788 5 12 theme UA 643:644 arg1 level 646:650 The UA level 639:650 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate 639:717 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 5 13 from level 646:650 arg1 oxidase 694:700 blood xanthine oxidase 679:700 blood xanthine oxidase (XOD) 679:706 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 5 13 from level 646:650 arg1 urate 713:717 urate 713:717 urate 713:717 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 5 13 from level 646:650 arg1 urine 662:666 urine 662:666 urine 662:666 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 5 13 from level 646:650 arg1 fecal 672:676 fecal 672:676 fecal 672:676 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 5 13 from level 646:650 arg1 XOD 703:705 XOD 703:705 XOD 703:705 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 5 13 from level 646:650 arg1 serum 655:659 serum 655:659 serum 655:659 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 7 14 theme hyperuricemia 915:927 arg1 group 929:933 the hyperuricemia group 911:933 the hyperuricemia group 911:933 RESULTS The UA level in the hyperuricemia group was significantly elevated (p<0.001), suggesting that the model was successfully established. 36424788 1 15 theme Intestinal 119:128 arg1 microbiota 130:139 BACKGROUND Intestinal microbiota 108:139 BACKGROUND Intestinal microbiota 108:139 BACKGROUND Intestinal microbiota is the primary target for the multifunctional nature of berberine. 36424788 1 15 theme Intestinal 119:128 arg1 target 156:161 the primary target 144:161 the primary target for the multifunctional nature of berberine 144:205 BACKGROUND Intestinal microbiota is the primary target for the multifunctional nature of berberine. 36424788 3 16 from effects 345:351 arg1 metabolism 384:393 uric acid (UA) metabolism 369:393 uric acid (UA) metabolism 369:393 This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. 36424788 3 16 from effects 345:351 arg1 microbiota 403:412 gut microbiota 399:412 gut microbiota 399:412 This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. 36424788 2 17 theme gut 263:265 arg1 microbiota 267:276 gut microbiota 263:276 gut microbiota 263:276 Berberine can reverse the structure and composition of gut microbiota under pathological conditions. 36424788 1 18 theme primary 148:154 arg1 microbiota 130:139 BACKGROUND Intestinal microbiota 108:139 BACKGROUND Intestinal microbiota 108:139 BACKGROUND Intestinal microbiota is the primary target for the multifunctional nature of berberine. 36424788 1 18 theme primary 148:154 arg1 target 156:161 the primary target 144:161 the primary target for the multifunctional nature of berberine 144:205 BACKGROUND Intestinal microbiota is the primary target for the multifunctional nature of berberine. 36424788 6 19 theme rRNA 870:873 arg1 sequencing 875:884 16S rRNA sequencing 866:884 16S rRNA sequencing 866:884 The alterations in gut microbiota were investigated using 16S rRNA sequencing. 36424788 3 20 theme uric 369:372 arg1 UA 380:381 UA 380:381 UA 380:381 This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. 36424788 3 20 theme uric 369:372 arg1 acid 374:377 uric acid 369:377 uric acid (UA) metabolism 369:393 This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. 36424788 4 21 theme male 508:511 arg1 rats 513:516 METHODS Sprague-Dawley (SD) male rats 480:516 METHODS Sprague-Dawley (SD) male rats 480:516 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 0 22 theme Hyperuricemia 82:94 arg1 Rats 96:99 Hyperuricemia Rats 82:99 Hyperuricemia Rats Model 82:105 Berberine Regulates the Metabolism of Uric Acid and Modulates Intestinal Flora in Hyperuricemia Rats Model. 36424788 9 23 theme XOD 1152:1154 arg1 level 1156:1160 The blood XOD level 1142:1160 The blood XOD level 1142:1160 The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). 36424788 3 24 theme berberine 356:364 arg1 effects 345:351 the effects 341:351 the effects of berberine on uric acid (UA) metabolism and gut microbiota 341:412 This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. 36424788 10 25 theme Further 1309:1315 arg1 sequencing 1321:1330 Further 16S sequencing 1309:1330 Further 16S sequencing 1309:1330 Further 16S sequencing revealed that berberine affected the gut microbiota composition and diversity in hyperuricemia rats. 36424788 7 26 dep RESULTS 887:893 arg1 elevated 953:960 elevated 953:960 elevated 953:960 RESULTS The UA level in the hyperuricemia group was significantly elevated (p<0.001), suggesting that the model was successfully established. 36424788 3 27 theme rat 433:435 arg1 model 437:441 a hyperuricemia rat model 417:441 a hyperuricemia rat model established using potassium oxonate 417:477 This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. 36424788 0 28 theme Uric 38:41 arg1 Acid 43:46 Uric Acid 38:46 Uric Acid 38:46 Berberine Regulates the Metabolism of Uric Acid and Modulates Intestinal Flora in Hyperuricemia Rats Model. 36424788 13 29 from candidate 1769:1777 arg1 hyperuricemia 1782:1794 hyperuricemia 1782:1794 hyperuricemia 1782:1794 CONCLUSION Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota. 36424788 4 30 theme Sprague-Dawley 488:501 arg1 rats 513:516 METHODS Sprague-Dawley (SD) male rats 480:516 METHODS Sprague-Dawley (SD) male rats 480:516 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 13 31 theme possible 1748:1755 arg1 Berberine 1727:1735 CONCLUSION Berberine 1716:1735 CONCLUSION Berberine 1716:1735 CONCLUSION Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota. 36424788 13 31 theme possible 1748:1755 arg1 candidate 1769:1777 a possible therapeutic candidate 1746:1777 a possible therapeutic candidate 1746:1777 CONCLUSION Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota. 36424788 9 32 theme urate 1173:1177 arg1 ABCG2 1189:1193 urate transport ABCG2 1173:1193 urate transport ABCG2 in the colon 1173:1206 The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). 36424788 4 33 theme normal 538:543 arg1 n= 560:561 n= 10 560:564 n= 10 560:564 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 4 33 theme normal 538:543 arg1 group 553:557 a normal control group 536:557 a normal control group (n= 10) 536:565 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 3 34 theme potassium 461:469 arg1 oxonate 471:477 potassium oxonate 461:477 potassium oxonate 461:477 This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. 36424788 10 35 from composition 1384:1394 arg1 rats 1427:1430 hyperuricemia rats 1413:1430 hyperuricemia rats 1413:1430 Further 16S sequencing revealed that berberine affected the gut microbiota composition and diversity in hyperuricemia rats. 36424788 8 36 dep decreased 1104:1112 arg1 p<0.001 1115:1121 p<0.001 1115:1121 p<0.001 1115:1121 After treatment with berberine, levels of blood and fecal UA significantly decreased (p<0.001), but not uric UA. 36424788 5 37 theme xanthine 685:692 arg1 oxidase 694:700 blood xanthine oxidase 679:700 blood xanthine oxidase (XOD) 679:706 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 5 37 theme xanthine 685:692 arg1 XOD 703:705 XOD 703:705 XOD 703:705 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 10 38 from diversity 1400:1408 arg1 rats 1427:1430 hyperuricemia rats 1413:1430 hyperuricemia rats 1413:1430 Further 16S sequencing revealed that berberine affected the gut microbiota composition and diversity in hyperuricemia rats. 36424788 12 39 theme sucrose 1682:1688 arg1 metabolism 1690:1699 starch and sucrose metabolism 1671:1699 metabolism 1690:1699 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 10 40 theme gut 1369:1371 arg1 composition 1384:1394 gut microbiota composition 1369:1394 gut microbiota composition 1369:1394 Further 16S sequencing revealed that berberine affected the gut microbiota composition and diversity in hyperuricemia rats. 36424788 13 41 theme gut 1896:1898 arg1 microbiota 1900:1909 gut microbiota 1896:1909 gut microbiota 1896:1909 CONCLUSION Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota. 36424788 0 42 theme Acid 43:46 arg1 Metabolism 24:33 the Metabolism 20:33 the Metabolism of Uric Acid 20:46 Berberine Regulates the Metabolism of Uric Acid and Modulates Intestinal Flora in Hyperuricemia Rats Model. 36424788 9 43 from Galectin-9 1239:1248 arg1 colon 1257:1261 the colon 1253:1261 the colon 1253:1261 The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). 36424788 11 44 theme Bacteroidetes 1487:1499 arg1 abundance 1474:1482 the relative abundance 1461:1482 the relative abundance of Bacteroidetes 1461:1499 Berberine treatment reduced the relative abundance of Bacteroidetes, and increased the relative abundance of Lactobacillus. 36424788 9 45 theme berberine 1279:1287 arg1 treatment 1289:1297 berberine treatment 1279:1297 berberine treatment (p<0.05) 1279:1306 The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). 36424788 9 45 theme berberine 1279:1287 arg1 p<0.05 1300:1305 p<0.05 1300:1305 p<0.05 1300:1305 The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). 36424788 9 46 theme transport 1229:1237 arg1 Galectin-9 1239:1248 urate transport Galectin-9 1223:1248 urate transport Galectin-9 in the colon 1223:1261 The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). 36424788 12 47 theme starch 1671:1676 arg1 metabolism 1690:1699 starch and sucrose metabolism 1671:1699 metabolism 1690:1699 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 10 48 theme hyperuricemia 1413:1425 arg1 rats 1427:1430 hyperuricemia rats 1413:1430 hyperuricemia rats 1413:1430 Further 16S sequencing revealed that berberine affected the gut microbiota composition and diversity in hyperuricemia rats. 36424788 11 49 theme Lactobacillus 1542:1554 arg1 abundance 1529:1537 the relative abundance 1516:1537 the relative abundance of Lactobacillus 1516:1554 Berberine treatment reduced the relative abundance of Bacteroidetes, and increased the relative abundance of Lactobacillus. 36424788 2 50 theme pathological 284:295 arg1 conditions 297:306 pathological conditions 284:306 pathological conditions 284:306 Berberine can reverse the structure and composition of gut microbiota under pathological conditions. 36424788 12 51 theme metabolic 1618:1626 arg1 N-glycans 1705:1713 N-glycans 1705:1713 N-glycans 1705:1713 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 12 51 theme metabolic 1618:1626 arg1 metabolism 1690:1699 starch and sucrose metabolism 1671:1699 metabolism 1690:1699 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 12 51 theme metabolic 1618:1626 arg1 metabolism 1659:1668 sphingolipid metabolism 1646:1668 sphingolipid metabolism 1646:1668 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 12 51 theme metabolic 1618:1626 arg1 pathways 1628:1635 multiple metabolic pathways 1609:1635 multiple metabolic pathways 1609:1635 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 4 52 theme berberine-treated 605:621 arg1 n 630:630 n = 11 630:635 n = 11 630:635 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 4 52 theme berberine-treated 605:621 arg1 group 623:627 a berberine-treated group 603:627 a berberine-treated group (n = 11) 603:636 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 1 53 theme berberine 197:205 arg1 nature 187:192 the multifunctional nature 167:192 the multifunctional nature of berberine 167:205 BACKGROUND Intestinal microbiota is the primary target for the multifunctional nature of berberine. 36424788 2 54 dep structure 234:242 arg1 the 230:232 the 230:232 the 230:232 Berberine can reverse the structure and composition of gut microbiota under pathological conditions. 36424788 10 55 dep composition 1384:1394 arg1 the 1365:1367 the 1365:1367 the 1365:1367 Further 16S sequencing revealed that berberine affected the gut microbiota composition and diversity in hyperuricemia rats. 36424788 7 56 theme UA 899:900 arg1 level 902:906 The UA level 895:906 The UA level in the hyperuricemia group 895:933 RESULTS The UA level in the hyperuricemia group was significantly elevated (p<0.001), suggesting that the model was successfully established. 36424788 1 57 theme BACKGROUND 108:117 arg1 microbiota 130:139 BACKGROUND Intestinal microbiota 108:139 BACKGROUND Intestinal microbiota 108:139 BACKGROUND Intestinal microbiota is the primary target for the multifunctional nature of berberine. 36424788 1 57 theme BACKGROUND 108:117 arg1 target 156:161 the primary target 144:161 the primary target for the multifunctional nature of berberine 144:205 BACKGROUND Intestinal microbiota is the primary target for the multifunctional nature of berberine. 36424788 8 58 theme UA 1087:1088 arg1 levels 1061:1066 levels 1061:1066 levels of blood and fecal UA 1061:1088 After treatment with berberine, levels of blood and fecal UA significantly decreased (p<0.001), but not uric UA. 36424788 2 59 theme microbiota 267:276 arg1 structure 234:242 structure 234:242 structure 234:242 Berberine can reverse the structure and composition of gut microbiota under pathological conditions. 36424788 2 59 theme microbiota 267:276 arg1 composition 248:258 composition 248:258 composition 248:258 Berberine can reverse the structure and composition of gut microbiota under pathological conditions. 36424788 5 60 theme ELISA 796:800 arg1 kits 802:805 ELISA kits 796:805 ELISA kits 796:805 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 0 61 theme Intestinal 62:71 arg1 Flora 73:77 Intestinal Flora 62:77 Intestinal Flora in Hyperuricemia Rats Model 62:105 Berberine Regulates the Metabolism of Uric Acid and Modulates Intestinal Flora in Hyperuricemia Rats Model. 36424788 7 62 from level 902:906 arg1 group 929:933 the hyperuricemia group 911:933 the hyperuricemia group 911:933 RESULTS The UA level in the hyperuricemia group was significantly elevated (p<0.001), suggesting that the model was successfully established. 36424788 13 63 theme therapeutic 1757:1767 arg1 Berberine 1727:1735 CONCLUSION Berberine 1716:1735 CONCLUSION Berberine 1716:1735 CONCLUSION Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota. 36424788 13 63 theme therapeutic 1757:1767 arg1 candidate 1769:1777 a possible therapeutic candidate 1746:1777 a possible therapeutic candidate 1746:1777 CONCLUSION Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota. 36424788 4 64 theme = 632:632 arg1 n 630:630 n = 11 630:635 n = 11 630:635 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 4 64 theme = 632:632 arg1 group 623:627 a berberine-treated group 603:627 a berberine-treated group (n = 11) 603:636 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 9 65 theme blood 1146:1150 arg1 level 1156:1160 The blood XOD level 1142:1160 The blood XOD level 1142:1160 The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). 36424788 12 66 theme gut 1561:1563 arg1 microbiota 1565:1574 The gut microbiota 1557:1574 The gut microbiota 1557:1574 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 6 67 theme 16S 866:868 arg1 sequencing 875:884 16S rRNA sequencing 866:884 16S rRNA sequencing 866:884 The alterations in gut microbiota were investigated using 16S rRNA sequencing. 36424788 3 68 theme acid 374:377 arg1 metabolism 384:393 uric acid (UA) metabolism 369:393 uric acid (UA) metabolism 369:393 This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. 36424788 4 69 theme METHODS 480:486 arg1 Sprague-Dawley 488:501 METHODS Sprague-Dawley 480:501 METHODS Sprague-Dawley (SD) male rats 480:516 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 4 69 theme METHODS 480:486 arg1 SD 504:505 SD 504:505 SD 504:505 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 9 70 from ABCG2 1189:1193 arg1 colon 1202:1206 the colon 1198:1206 the colon 1198:1206 The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). 36424788 0 71 dep Rats 96:99 arg1 Model 101:105 Model 101:105 Hyperuricemia Rats Model 82:105 Berberine Regulates the Metabolism of Uric Acid and Modulates Intestinal Flora in Hyperuricemia Rats Model. 36424788 4 72 theme control 545:551 arg1 n= 560:561 n= 10 560:564 n= 10 560:564 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 4 72 theme control 545:551 arg1 group 553:557 a normal control group 536:557 a normal control group (n= 10) 536:565 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 8 73 with treatment 1035:1043 arg1 berberine 1050:1058 berberine 1050:1058 berberine 1050:1058 After treatment with berberine, levels of blood and fecal UA significantly decreased (p<0.001), but not uric UA. 36424788 3 74 theme hyperuricemia 419:431 arg1 model 437:441 a hyperuricemia rat model 417:441 a hyperuricemia rat model established using potassium oxonate 417:477 This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. 36424788 9 75 theme transport 1179:1187 arg1 ABCG2 1189:1193 urate transport ABCG2 1173:1193 urate transport ABCG2 in the colon 1173:1206 The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). 36424788 13 76 theme CONCLUSION 1716:1725 arg1 Berberine 1727:1735 CONCLUSION Berberine 1716:1735 CONCLUSION Berberine 1716:1735 CONCLUSION Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota. 36424788 13 76 theme CONCLUSION 1716:1725 arg1 candidate 1769:1777 a possible therapeutic candidate 1746:1777 a possible therapeutic candidate 1746:1777 CONCLUSION Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota. 36424788 5 77 theme blood 679:683 arg1 oxidase 694:700 blood xanthine oxidase 679:700 blood xanthine oxidase (XOD) 679:706 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 5 77 theme blood 679:683 arg1 XOD 703:705 XOD 703:705 XOD 703:705 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 10 78 theme 16S 1317:1319 arg1 sequencing 1321:1330 Further 16S sequencing 1309:1330 Further 16S sequencing 1309:1330 Further 16S sequencing revealed that berberine affected the gut microbiota composition and diversity in hyperuricemia rats. 36424788 3 79 theme gut 399:401 arg1 microbiota 403:412 gut microbiota 399:412 gut microbiota 399:412 This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. 36424788 11 80 theme Berberine 1433:1441 arg1 treatment 1443:1451 Berberine treatment 1433:1451 Berberine treatment 1433:1451 Berberine treatment reduced the relative abundance of Bacteroidetes, and increased the relative abundance of Lactobacillus. 36424788 4 81 theme hyperuricemia 570:582 arg1 n 591:591 n = 12 591:596 n = 12 591:596 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 4 81 theme hyperuricemia 570:582 arg1 group 584:588 a hyperuricemia group 568:588 a hyperuricemia group (n = 12) 568:597 METHODS Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). 36424788 6 82 from alterations 812:822 arg1 microbiota 831:840 gut microbiota 827:840 gut microbiota 827:840 The alterations in gut microbiota were investigated using 16S rRNA sequencing. 36424788 9 83 theme urate 1223:1227 arg1 Galectin-9 1239:1248 urate transport Galectin-9 1223:1248 urate transport Galectin-9 in the colon 1223:1261 The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). 36424788 12 84 theme sphingolipid 1646:1657 arg1 metabolism 1659:1668 sphingolipid metabolism 1646:1668 sphingolipid metabolism 1646:1668 The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. 36424788 5 85 dep transports 719:728 arg1 evaluated 780:788 evaluated 780:788 were evaluated using ELISA kits 775:805 The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. 36424788 11 86 theme relative 1465:1472 arg1 abundance 1474:1482 the relative abundance 1461:1482 the relative abundance of Bacteroidetes 1461:1499 Berberine treatment reduced the relative abundance of Bacteroidetes, and increased the relative abundance of Lactobacillus. 36060749 7 0 theme organic 1234:1240 arg1 carbon 1242:1247 total organic carbon 1228:1247 total organic carbon 1228:1247 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 4 1 theme EPSs 597:600 arg1 preservation 581:592 the preservation 577:592 the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary 577:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 3 2 from column 530:535 arg1 absent 497:502 absent 497:502 absent 497:502 In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. 36060749 4 3 theme EPS-mineral 606:616 arg1 aggregates 618:627 EPS-mineral aggregates 606:627 EPS-mineral aggregates 606:627 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 4 4 from bar 693:695 arg1 Estuary 712:718 Estuary 712:718 Estuary 712:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 4 5 theme estuarine 677:685 arg1 bar 693:695 an estuarine point bar 674:695 an estuarine point bar in the Gironde Estuary 674:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 10 6 theme EPS 1734:1736 arg1 abundant 1767:1774 abundant 1767:1774 abundant 1767:1774 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 10 6 theme EPS 1734:1736 arg1 complexes 1738:1746 the EPS complexes 1730:1746 the EPS complexes with sediment 1730:1760 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 8 7 from reactivity 1392:1401 arg1 concentrations 1342:1355 EPS concentrations 1338:1355 EPS concentrations (proteins and polysaccharides) 1338:1386 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 14 8 theme EPS 2357:2359 arg1 production 2361:2370 EPS production 2357:2370 EPS production 2357:2370 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 8 theme EPS 2357:2359 arg1 areas 2426:2430 the intertidal areas 2411:2430 the intertidal areas 2411:2430 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 8 theme EPS 2357:2359 arg1 extensive 2446:2454 extensive 2446:2454 extensive 2446:2454 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 8 theme EPS 2357:2359 arg1 bar 2403:2405 the point bar 2393:2405 the point bar 2393:2405 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 8 theme EPS 2357:2359 arg1 development 2341:2351 biofilm development 2333:2351 biofilm development 2333:2351 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 10 9 theme depth 1580:1584 arg1 EPSs 1586:1589 depth EPSs 1580:1589 depth EPSs abundance 1580:1599 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 13 10 theme EPS 2109:2111 arg1 concentrations 2113:2126 Maximum EPS concentrations 2101:2126 Maximum EPS concentrations 2101:2126 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 4 11 from core 655:658 arg1 evidence 565:572 the first evidence 555:572 the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary 555:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 8 12 dep concentrations 1342:1355 arg1 polysaccharides 1371:1385 polysaccharides 1371:1385 polysaccharides 1371:1385 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 8 12 dep concentrations 1342:1355 arg1 proteins 1358:1365 proteins 1358:1365 proteins 1358:1365 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 12 13 theme EPS 1935:1937 arg1 concentrations 1939:1952 EPS concentrations 1935:1952 EPS concentrations 1935:1952 EPS concentrations and acidity were anti-correlated with metabolic activity, but showed no statistical correlation with grain size, TOC, depth or enzymatic activity. 36060749 14 14 dep sequences 2478:2486 arg1 i.e. 2457:2460 i.e. 2457:2460 i.e. 2457:2460 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 10 15 dep at 1572:1573 arg1 showed 1635:1640 showed 1635:1640 showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) 1635:1716 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 10 15 dep at 1572:1573 arg1 comparable 1605:1614 comparable 1605:1614 comparable 1605:1614 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 13 16 located found 2224:2228 arg1 sequences 2267:2275 river flood-dominated sedimentary sequences 2233:2275 river flood-dominated sedimentary sequences 2233:2275 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 13 16 located found 2224:2228 arg2 concentrations 2204:2217 very low concentrations 2195:2217 very low concentrations 2195:2217 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 5 17 theme chemical 848:855 arg1 assays 857:862 wet chemical assays 844:862 (i) wet chemical assays to measure the concentrations of polysaccharides and proteins 840:924 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 8 18 theme 0.5 m 1442:1446 arg1 depth 1433:1437 a depth 1431:1437 a depth of 0.5 m 1431:1446 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 10 19 theme studied 1783:1789 arg1 depth 1791:1795 all studied depth 1779:1795 all studied depth 1779:1795 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 1 20 theme diatom 126:131 arg1 biofilms 133:140 diatom biofilms 126:140 diatom biofilms 126:140 The surface of intertidal estuarine sediments is covered with diatom biofilms excreting exopolymeric substances (EPSs) through photosynthesis. 36060749 3 21 theme sedimentary 326:336 arg1 environments 338:349 most sedimentary environments 321:349 most sedimentary environments 321:349 In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. 36060749 14 22 theme biofilm 2333:2339 arg1 production 2361:2370 EPS production 2357:2370 EPS production 2357:2370 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 22 theme biofilm 2333:2339 arg1 areas 2426:2430 the intertidal areas 2411:2430 the intertidal areas 2411:2430 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 22 theme biofilm 2333:2339 arg1 extensive 2446:2454 extensive 2446:2454 extensive 2446:2454 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 22 theme biofilm 2333:2339 arg1 bar 2403:2405 the point bar 2393:2405 the point bar 2393:2405 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 22 theme biofilm 2333:2339 arg1 development 2341:2351 biofilm development 2333:2351 biofilm development 2333:2351 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 5 23 theme EPS 931:933 arg1 deprotonation 935:947 EPS deprotonation 931:947 EPS deprotonation of functional groups 931:968 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 12 24 theme grain 2055:2059 arg1 size 2061:2064 grain size 2055:2064 grain size 2055:2064 EPS concentrations and acidity were anti-correlated with metabolic activity, but showed no statistical correlation with grain size, TOC, depth or enzymatic activity. 36060749 7 25 theme total 1228:1232 arg1 carbon 1242:1247 total organic carbon 1228:1247 total organic carbon 1228:1247 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 4 26 from evidence 565:572 arg1 core 655:658 a 6-m-long sedimentary core 632:658 a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary 632:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 13 27 theme sedimentary 2255:2265 arg1 sequences 2267:2275 river flood-dominated sedimentary sequences 2233:2275 river flood-dominated sedimentary sequences 2233:2275 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 14 28 theme burial 2548:2553 arg1 sediments 2563:2571 rapid burial beneath sediments 2542:2571 rapid burial beneath sediments 2542:2571 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 3 29 theme heterotrophic 389:401 arg1 bacteria 403:410 heterotrophic bacteria 389:410 heterotrophic bacteria in the uppermost millimeters of the sediment 389:455 In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. 36060749 0 30 from Preservation 0:11 arg1 sediments 53:61 estuarine sediments 43:61 estuarine sediments 43:61 Preservation of exopolymeric substances in estuarine sediments. 36060749 8 31 theme EPS 1338:1340 arg1 concentrations 1342:1355 EPS concentrations 1338:1355 EPS concentrations (proteins and polysaccharides) 1338:1386 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 7 32 theme grain 1212:1216 arg1 size 1218:1221 grain size 1212:1221 grain size 1212:1221 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 9 33 theme 4.3 m 1546:1550 arg1 deep 1552:1555 ca. 4.3 m deep 1542:1555 ca. 4.3 m deep 1542:1555 Concentrations remained relatively low down to ca. 4.3 m deep. 36060749 10 34 from depth 1791:1795 arg1 abundant 1767:1774 abundant 1767:1774 abundant 1767:1774 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 10 34 from depth 1791:1795 arg1 complexes 1738:1746 the EPS complexes 1730:1746 the EPS complexes with sediment 1730:1760 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 10 35 theme downward 1644:1651 arg1 decrease 1653:1660 a downward decrease 1642:1660 a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) 1642:1716 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 8 36 from decrease 1326:1333 arg1 concentrations 1342:1355 EPS concentrations 1338:1355 EPS concentrations (proteins and polysaccharides) 1338:1386 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 1 37 theme intertidal 79:88 arg1 sediments 100:108 intertidal estuarine sediments 79:108 intertidal estuarine sediments 79:108 The surface of intertidal estuarine sediments is covered with diatom biofilms excreting exopolymeric substances (EPSs) through photosynthesis. 36060749 3 38 theme uppermost 419:427 arg1 millimeters 429:439 the uppermost millimeters 415:439 the uppermost millimeters of the sediment 415:455 In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. 36060749 14 39 dep maximal 2376:2382 arg1 bar 2403:2405 the point bar 2393:2405 the point bar 2393:2405 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 39 dep maximal 2376:2382 arg1 development 2341:2351 biofilm development 2333:2351 biofilm development 2333:2351 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 39 dep maximal 2376:2382 arg1 extensive 2446:2454 extensive 2446:2454 extensive 2446:2454 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 39 dep maximal 2376:2382 arg1 i 2390:2390 i 2390:2390 i 2390:2390 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 39 dep maximal 2376:2382 arg1 succeeded 2529:2537 succeeded 2529:2537 were succeeded by rapid burial beneath sediments 2524:2571 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 39 dep maximal 2376:2382 arg1 areas 2426:2430 the intertidal areas 2411:2430 the intertidal areas 2411:2430 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 39 dep maximal 2376:2382 arg1 production 2361:2370 EPS production 2357:2370 EPS production 2357:2370 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 7 40 theme properties 1183:1192 arg1 context 1163:1169 the context 1159:1169 the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities 1159:1290 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 1 41 theme sediments 100:108 arg1 surface 68:74 The surface 64:74 The surface of intertidal estuarine sediments 64:108 The surface of intertidal estuarine sediments is covered with diatom biofilms excreting exopolymeric substances (EPSs) through photosynthesis. 36060749 6 42 theme EPS-sediment 1049:1060 arg1 complexes 1062:1070 EPS-sediment complexes 1049:1070 EPS-sediment complexes 1049:1070 EPS-sediment complexes were also imaged using cryo-scanning electron microscopy. 36060749 10 43 theme cryo-scanning 1673:1685 arg1 Cryo-SEM 1708:1715 Cryo-SEM 1708:1715 Cryo-SEM 1708:1715 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 10 43 theme cryo-scanning 1673:1685 arg1 microscopy 1696:1705 cryo-scanning electron microscopy 1673:1705 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) 1665:1716 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 0 44 theme exopolymeric 16:27 arg1 substances 29:38 exopolymeric substances 16:38 exopolymeric substances 16:38 Preservation of exopolymeric substances in estuarine sediments. 36060749 5 45 theme groups 963:968 arg1 deprotonation 935:947 EPS deprotonation 931:947 EPS deprotonation of functional groups 931:968 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 5 45 theme groups 963:968 arg1 titrations 986:995 (ii) acid-base titrations 971:995 (ii) acid-base titrations 971:995 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 5 45 theme groups 963:968 arg1 assays 857:862 wet chemical assays 844:862 (i) wet chemical assays to measure the concentrations of polysaccharides and proteins 840:924 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 5 45 theme groups 963:968 arg1 Fourier 1008:1014 (iii) Fourier 1002:1014 (iii) Fourier transform infrared spectroscopy 1002:1046 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 13 46 theme flood-dominated 2239:2253 arg1 sequences 2267:2275 river flood-dominated sedimentary sequences 2233:2275 river flood-dominated sedimentary sequences 2233:2275 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 3 47 theme sediment 448:455 arg1 millimeters 429:439 the uppermost millimeters 415:439 the uppermost millimeters of the sediment 415:455 In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. 36060749 5 48 dep assays 857:862 arg1 i 841:841 i 841:841 i 841:841 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 5 48 dep assays 857:862 arg1 measure 867:873 measure 867:873 to measure the concentrations of polysaccharides and proteins 864:924 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 14 49 theme intertidal 2415:2424 arg1 bar 2403:2405 the point bar 2393:2405 the point bar 2393:2405 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 49 theme intertidal 2415:2424 arg1 development 2341:2351 biofilm development 2333:2351 biofilm development 2333:2351 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 49 theme intertidal 2415:2424 arg1 extensive 2446:2454 extensive 2446:2454 extensive 2446:2454 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 49 theme intertidal 2415:2424 arg1 i 2390:2390 i 2390:2390 i 2390:2390 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 49 theme intertidal 2415:2424 arg1 areas 2426:2430 the intertidal areas 2411:2430 the intertidal areas 2411:2430 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 49 theme intertidal 2415:2424 arg1 production 2361:2370 EPS production 2357:2370 EPS production 2357:2370 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 13 50 theme low 2200:2202 arg1 concentrations 2204:2217 very low concentrations 2195:2217 very low concentrations 2195:2217 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 7 51 theme enzymatic 1271:1279 arg1 activities 1281:1290 metabolic and enzymatic activities 1257:1290 metabolic and enzymatic activities 1257:1290 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 3 52 from absent 497:502 arg1 column 530:535 the sedimentary column 514:535 the sedimentary column 514:535 In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. 36060749 13 53 theme tide-dominated 2153:2166 arg1 sequences 2180:2188 tide-dominated sedimentary sequences 2153:2188 tide-dominated sedimentary sequences 2153:2188 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 7 54 theme metabolic 1257:1265 arg1 activities 1281:1290 metabolic and enzymatic activities 1257:1290 metabolic and enzymatic activities 1257:1290 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 4 55 theme aggregates 618:627 arg1 preservation 581:592 the preservation 577:592 the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary 577:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 14 56 theme point 2397:2401 arg1 bar 2403:2405 the point bar 2393:2405 the point bar 2393:2405 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 56 theme point 2397:2401 arg1 development 2341:2351 biofilm development 2333:2351 biofilm development 2333:2351 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 56 theme point 2397:2401 arg1 extensive 2446:2454 extensive 2446:2454 extensive 2446:2454 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 56 theme point 2397:2401 arg1 i 2390:2390 i 2390:2390 i 2390:2390 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 56 theme point 2397:2401 arg1 areas 2426:2430 the intertidal areas 2411:2430 the intertidal areas 2411:2430 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 56 theme point 2397:2401 arg1 production 2361:2370 EPS production 2357:2370 EPS production 2357:2370 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 13 57 theme sequences 2180:2188 arg1 top 2146:2148 the top 2142:2148 the top of tide-dominated sedimentary sequences 2142:2188 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 14 58 theme tide-dominated 2463:2476 arg1 sequences 2478:2486 tide-dominated sequences 2463:2486 tide-dominated sequences 2463:2486 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 6 59 theme cryo-scanning 1095:1107 arg1 microscopy 1118:1127 cryo-scanning electron microscopy 1095:1127 cryo-scanning electron microscopy 1095:1127 EPS-sediment complexes were also imaged using cryo-scanning electron microscopy. 36060749 7 60 theme EPS 1130:1132 arg1 results 1134:1140 EPS results 1130:1140 EPS results 1130:1140 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 12 61 theme statistical 2026:2036 arg1 correlation 2038:2048 no statistical correlation 2023:2048 no statistical correlation 2023:2048 EPS concentrations and acidity were anti-correlated with metabolic activity, but showed no statistical correlation with grain size, TOC, depth or enzymatic activity. 36060749 12 62 theme metabolic 1992:2000 arg1 activity 2002:2009 metabolic activity 1992:2009 metabolic activity 1992:2009 EPS concentrations and acidity were anti-correlated with metabolic activity, but showed no statistical correlation with grain size, TOC, depth or enzymatic activity. 36060749 5 63 dep Fourier 1008:1014 arg1 iii 1003:1005 iii 1003:1005 iii 1003:1005 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 5 63 dep Fourier 1008:1014 arg1 transform 1016:1024 transform 1016:1024 transform infrared spectroscopy 1016:1046 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 14 64 theme bacterial 2634:2642 arg1 cells 2644:2648 bacterial cells 2634:2648 bacterial cells 2634:2648 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 4 65 theme point 687:691 arg1 bar 693:695 an estuarine point bar 674:695 an estuarine point bar in the Gironde Estuary 674:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 10 66 theme EPSs 1586:1589 arg1 abundance 1591:1599 depth EPSs abundance 1580:1599 depth EPSs abundance 1580:1599 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 14 67 theme encounter 2616:2624 arg1 probability 2601:2611 the probability 2597:2611 the probability of encounter between bacterial cells and EPSs 2597:2657 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 3 68 theme most 321:324 arg1 environments 338:349 most sedimentary environments 321:349 most sedimentary environments 321:349 In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. 36060749 4 69 theme sedimentary 643:653 arg1 core 655:658 a 6-m-long sedimentary core 632:658 a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary 632:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 2 70 theme sediment 251:258 arg1 cohesiveness 260:271 sediment cohesiveness 251:271 sediment cohesiveness 251:271 These EPSs are highly reactive and increase sediment cohesiveness notably through organo-mineral interactions. 36060749 5 71 theme wet 844:846 arg1 assays 857:862 wet chemical assays 844:862 (i) wet chemical assays to measure the concentrations of polysaccharides and proteins 840:924 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 5 72 dep titrations 986:995 arg1 ii 972:973 ii 972:973 ii 972:973 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 3 73 from bacteria 403:410 arg1 millimeters 429:439 the uppermost millimeters 415:439 the uppermost millimeters of the sediment 415:455 In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. 36060749 5 74 theme proteins 917:924 arg1 concentrations 879:892 the concentrations 875:892 the concentrations of polysaccharides and proteins 875:924 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 2 75 theme organo-mineral 289:302 arg1 interactions 304:315 organo-mineral interactions 289:315 organo-mineral interactions 289:315 These EPSs are highly reactive and increase sediment cohesiveness notably through organo-mineral interactions. 36060749 10 76 with complexes 1738:1746 arg1 sediment 1753:1760 sediment 1753:1760 sediment 1753:1760 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 8 77 theme heterotrophic 1468:1480 arg1 degradation 1482:1492 heterotrophic degradation 1468:1492 heterotrophic degradation 1468:1492 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 13 78 theme Maximum 2101:2107 arg1 concentrations 2113:2126 Maximum EPS concentrations 2101:2126 Maximum EPS concentrations 2101:2126 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 1 79 theme exopolymeric 152:163 arg1 substances 165:174 exopolymeric substances 152:174 exopolymeric substances (EPSs) 152:181 The surface of intertidal estuarine sediments is covered with diatom biofilms excreting exopolymeric substances (EPSs) through photosynthesis. 36060749 1 79 theme exopolymeric 152:163 arg1 EPSs 177:180 EPSs 177:180 EPSs 177:180 The surface of intertidal estuarine sediments is covered with diatom biofilms excreting exopolymeric substances (EPSs) through photosynthesis. 36060749 14 80 theme beneath 2555:2561 arg1 sediments 2563:2571 rapid burial beneath sediments 2542:2571 rapid burial beneath sediments 2542:2571 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 5 81 theme polysaccharides 897:911 arg1 concentrations 879:892 the concentrations 875:892 the concentrations of polysaccharides and proteins 875:924 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 14 82 theme rapid 2542:2546 arg1 sediments 2563:2571 rapid burial beneath sediments 2542:2571 rapid burial beneath sediments 2542:2571 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 83 dep extensive 2446:2454 arg1 areas 2426:2430 the intertidal areas 2411:2430 the intertidal areas 2411:2430 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 83 dep extensive 2446:2454 arg1 extensive 2446:2454 extensive 2446:2454 extensive 2446:2454 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 83 dep extensive 2446:2454 arg1 bar 2403:2405 the point bar 2393:2405 the point bar 2393:2405 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 14 83 dep extensive 2446:2454 arg1 i 2390:2390 i 2390:2390 i 2390:2390 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 8 84 theme predictable 1314:1324 arg1 decrease 1326:1333 a predictable decrease 1312:1333 a predictable decrease in EPS concentrations (proteins and polysaccharides) 1312:1386 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 9 85 theme ca. 1542:1544 arg1 deep 1552:1555 ca. 4.3 m deep 1542:1555 ca. 4.3 m deep 1542:1555 Concentrations remained relatively low down to ca. 4.3 m deep. 36060749 8 86 from biofilm 1420:1426 arg1 reactivity 1392:1401 reactivity 1392:1401 reactivity from the surface biofilm 1392:1426 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 8 86 from biofilm 1420:1426 arg1 decrease 1326:1333 a predictable decrease 1312:1333 a predictable decrease in EPS concentrations (proteins and polysaccharides) 1312:1386 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 10 87 theme electron 1687:1694 arg1 Cryo-SEM 1708:1715 Cryo-SEM 1708:1715 Cryo-SEM 1708:1715 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 10 87 theme electron 1687:1694 arg1 microscopy 1696:1705 cryo-scanning electron microscopy 1673:1705 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) 1665:1716 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 5 88 theme depth 749:753 arg1 intervals 755:763 18 depth intervals 746:763 18 depth intervals along the core 746:778 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 12 89 theme enzymatic 2081:2089 arg1 activity 2091:2098 enzymatic activity 2081:2098 enzymatic activity 2081:2098 EPS concentrations and acidity were anti-correlated with metabolic activity, but showed no statistical correlation with grain size, TOC, depth or enzymatic activity. 36060749 7 90 theme sediment 1174:1181 arg1 size 1218:1221 grain size 1212:1221 grain size 1212:1221 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 7 90 theme sediment 1174:1181 arg1 carbon 1242:1247 total organic carbon 1228:1247 total organic carbon 1228:1247 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 7 90 theme sediment 1174:1181 arg1 facies 1204:1209 facies 1204:1209 facies 1204:1209 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 7 90 theme sediment 1174:1181 arg1 properties 1183:1192 sediment properties 1174:1192 sediment properties including facies, grain size, and total organic carbon 1174:1247 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 1 91 theme estuarine 90:98 arg1 sediments 100:108 intertidal estuarine sediments 79:108 intertidal estuarine sediments 79:108 The surface of intertidal estuarine sediments is covered with diatom biofilms excreting exopolymeric substances (EPSs) through photosynthesis. 36060749 0 92 theme substances 29:38 arg1 Preservation 0:11 Preservation 0:11 Preservation of exopolymeric substances in estuarine sediments. 0:62 Preservation of exopolymeric substances in estuarine sediments. 36060749 5 93 theme functional 952:961 arg1 groups 963:968 functional groups 952:968 functional groups 952:968 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 4 94 theme preservation 581:592 arg1 evidence 565:572 the first evidence 555:572 the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary 555:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 3 95 dep partly 361:366 arg1 to 368:369 to 368:369 to 368:369 In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. 36060749 11 96 theme core 1929:1932 arg1 bottom 1915:1920 the bottom 1911:1920 the bottom of the core 1911:1932 EPS composition did not change substantially from the surface to the bottom of the core. 36060749 0 97 theme estuarine 43:51 arg1 sediments 53:61 estuarine sediments 43:61 estuarine sediments 43:61 Preservation of exopolymeric substances in estuarine sediments. 36060749 13 98 theme river 2233:2237 arg1 sequences 2267:2275 river flood-dominated sedimentary sequences 2233:2275 river flood-dominated sedimentary sequences 2233:2275 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 14 99 theme tide-dominated 2501:2514 arg1 deposit 2516:2522 the tide-dominated deposit 2497:2522 the tide-dominated deposit 2497:2522 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 7 100 theme activities 1281:1290 arg1 context 1163:1169 the context 1159:1169 the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities 1159:1290 EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. 36060749 5 101 theme physicochemical 791:805 arg1 properties 807:816 their physicochemical properties 785:816 their physicochemical properties 785:816 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 4 102 theme first 559:563 arg1 evidence 565:572 the first evidence 555:572 the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary 555:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 10 103 dep 6.08 m. 1665:1671 arg1 Cryo-SEM 1708:1715 Cryo-SEM 1708:1715 Cryo-SEM 1708:1715 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 10 103 dep 6.08 m. 1665:1671 arg1 microscopy 1696:1705 cryo-scanning electron microscopy 1673:1705 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) 1665:1716 Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. 36060749 3 104 theme sedimentary 518:528 arg1 column 530:535 the sedimentary column 514:535 the sedimentary column 514:535 In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. 36060749 5 105 theme acid-base 976:984 arg1 titrations 986:995 (ii) acid-base titrations 971:995 (ii) acid-base titrations 971:995 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36060749 14 106 dep succeeded 2529:2537 arg1 ii 2493:2494 ii 2493:2494 ii 2493:2494 Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs. 36060749 8 107 theme surface 1412:1418 arg1 biofilm 1420:1426 the surface biofilm 1408:1426 the surface biofilm 1408:1426 Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. 36060749 11 108 theme EPS 1846:1848 arg1 composition 1850:1860 EPS composition 1846:1860 EPS composition 1846:1860 EPS composition did not change substantially from the surface to the bottom of the core. 36060749 13 109 located found 2133:2137 arg1 top 2146:2148 the top 2142:2148 the top of tide-dominated sedimentary sequences 2142:2188 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 13 109 located found 2133:2137 arg2 concentrations 2113:2126 Maximum EPS concentrations 2101:2126 Maximum EPS concentrations 2101:2126 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 13 110 theme sedimentary 2168:2178 arg1 sequences 2180:2188 tide-dominated sedimentary sequences 2153:2188 tide-dominated sedimentary sequences 2153:2188 Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. 36060749 6 111 theme electron 1109:1116 arg1 microscopy 1118:1127 cryo-scanning electron microscopy 1095:1127 cryo-scanning electron microscopy 1095:1127 EPS-sediment complexes were also imaged using cryo-scanning electron microscopy. 36060749 4 112 theme 6-m-long 634:641 arg1 core 655:658 a 6-m-long sedimentary core 632:658 a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary 632:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 4 113 from preservation 581:592 arg1 core 655:658 a 6-m-long sedimentary core 632:658 a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary 632:718 Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. 36060749 5 114 dep transform 1016:1024 arg1 infrared 1026:1033 infrared 1026:1033 transform infrared spectroscopy 1016:1046 EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid-base titrations, and (iii) Fourier transform infrared spectroscopy. 36042157 9 0 theme CHPF 1678:1681 arg1 high-expression 1692:1706 CHPF abnormal high-expression 1678:1706 CHPF abnormal high-expression 1678:1706 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 4 1 with effect 685:690 arg1 features 629:636 the clinicopathological features 605:636 the clinicopathological features of breast cancer (BRCA) 605:660 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 9 2 theme TNBC 1659:1662 arg1 patients 1664:1671 refractory TNBC patients 1648:1671 refractory TNBC patients with CHPF abnormal high-expression 1648:1706 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 2 3 theme chondroitin 368:378 arg1 CS 389:390 CS 389:390 CS 389:390 Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). 36042157 2 3 theme chondroitin 368:378 arg1 sulfate 380:386 chondroitin sulfate 368:386 chondroitin sulfate (CS) 368:391 Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). 36042157 0 4 theme cancer 78:83 arg1 progression 85:95 breast cancer progression 71:95 breast cancer progression 71:95 Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation. 36042157 3 5 with interaction 496:506 arg1 TME 529:531 TME 529:531 TME 529:531 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 1 6 from composition 161:171 arg1 TME 215:217 TME 215:217 TME 215:217 Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. 36042157 1 6 from composition 161:171 arg1 microenvironment 197:212 the tumor microenvironment 187:212 the tumor microenvironment (TME) 187:218 Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. 36042157 7 7 theme mechanistic 1069:1079 arg1 study 1081:1085 The mechanistic study 1065:1085 The mechanistic study 1065:1085 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 9 8 dep novel 1619:1623 arg1 therapeutic 1625:1635 therapeutic 1625:1635 therapeutic 1625:1635 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 6 9 theme tumor 982:986 arg1 mass 988:991 tumor mass 982:991 tumor mass 982:991 The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. 36042157 9 10 theme signaling 1595:1603 arg1 blockade 1554:1561 Pharmacological blockade 1538:1561 Pharmacological blockade of the upstream of JNK or SMAD3 signaling 1538:1603 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 4 11 theme cancer 648:653 arg1 features 629:636 the clinicopathological features 605:636 the clinicopathological features of breast cancer (BRCA) 605:660 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 7 12 theme TGF-β1-induced 1169:1182 arg1 SMAD3 1184:1188 TGF-β1-induced SMAD3 1169:1188 TGF-β1-induced SMAD3 1169:1188 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 7 13 theme triple-negative 1384:1398 arg1 TNBC 1415:1418 TNBC 1415:1418 TNBC 1415:1418 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 7 13 theme triple-negative 1384:1398 arg1 cancer 1407:1412 triple-negative breast cancer 1384:1412 triple-negative breast cancer (TNBC) 1384:1419 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 6 14 theme poor 933:936 arg1 prognosis 938:946 a poor prognosis 931:946 a poor prognosis 931:946 The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. 36042157 4 15 theme CHPF 724:727 arg1 mechanisms 710:719 the underling mechanisms 696:719 the underling mechanisms 696:719 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 4 15 theme CHPF 724:727 arg1 association 569:579 the association 565:579 the association of CHPF expression with the clinicopathological features of breast cancer (BRCA) 565:660 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 4 15 theme CHPF 724:727 arg1 effect 685:690 the oncogenic effect 671:690 the oncogenic effect 671:690 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 9 16 theme abnormal 1683:1690 arg1 high-expression 1692:1706 CHPF abnormal high-expression 1678:1706 CHPF abnormal high-expression 1678:1706 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 3 17 theme crucial 472:478 arg1 mediator 480:487 a crucial mediator 470:487 a crucial mediator in the interaction of cancer cells with TME 470:531 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 3 17 theme crucial 472:478 arg1 expression 458:467 transforming growth factor-β1 (TGF-β1) expression 419:467 transforming growth factor-β1 (TGF-β1) expression 419:467 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 5 18 theme TGF-β 863:867 arg1 expression 869:878 TGF-β expression 863:878 TGF-β expression (r = 0.7125) 863:891 We found that CHPF expression is significantly increased in human BRCA tissues, and it is positively associated with TGF-β expression (r = 0.7125). 36042157 5 18 theme TGF-β 863:867 arg1 r = 0.7125 881:890 r = 0.7125 881:890 r = 0.7125 881:890 We found that CHPF expression is significantly increased in human BRCA tissues, and it is positively associated with TGF-β expression (r = 0.7125). 36042157 6 19 theme HER-2 1038:1042 arg1 negative-expression 1044:1062 HER-2 negative-expression 1038:1062 HER-2 negative-expression 1038:1062 The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. 36042157 5 20 theme CHPF 760:763 arg1 expression 765:774 CHPF expression 760:774 CHPF expression 760:774 We found that CHPF expression is significantly increased in human BRCA tissues, and it is positively associated with TGF-β expression (r = 0.7125). 36042157 3 21 theme cells 518:522 arg1 interaction 496:506 the interaction 492:506 the interaction of cancer cells with TME 492:531 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 1 22 theme glycans 176:182 arg1 composition 161:171 Aberrant composition 152:171 Aberrant composition of glycans in the tumor microenvironment (TME) 152:218 Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. 36042157 0 23 theme upstream 105:112 arg1 TGF-β1/SMAD3 114:125 the upstream TGF-β1/SMAD3 and JNK axis activation 101:149 TGF-β1/SMAD3 114:125 Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation. 36042157 9 24 theme SMAD3 1589:1593 arg1 upstream 1570:1577 upstream 1570:1577 upstream 1570:1577 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 9 25 theme Pharmacological 1538:1552 arg1 blockade 1554:1561 Pharmacological blockade 1538:1561 Pharmacological blockade of the upstream of JNK or SMAD3 signaling 1538:1603 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 2 26 theme polymerizing 281:292 arg1 CHPF 302:305 CHPF 302:305 CHPF 302:305 Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). 36042157 2 26 theme polymerizing 281:292 arg1 factor 294:299 Chondroitin polymerizing factor 269:299 Chondroitin polymerizing factor (CHPF) 269:306 Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). 36042157 2 26 theme polymerizing 281:292 arg1 glycosyltransferase 313:331 a glycosyltransferase 311:331 a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS) 311:391 Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). 36042157 4 27 theme breast 641:646 arg1 cancer 648:653 breast cancer 641:653 breast cancer (BRCA) 641:660 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 4 27 theme breast 641:646 arg1 BRCA 656:659 BRCA 656:659 BRCA 656:659 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 0 28 theme polymerizing 12:23 arg1 factor 25:30 Chondroitin polymerizing factor 0:30 Chondroitin polymerizing factor 0:30 Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation. 36042157 3 29 theme cancer 511:516 arg1 cells 518:522 cancer cells 511:522 cancer cells 511:522 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 7 30 theme SMAD3 1237:1241 arg1 inhibitor 1250:1258 JNK (SP600125) or SMAD3 (SIS3) inhibitor 1219:1258 JNK (SP600125) or SMAD3 (SIS3) inhibitor 1219:1258 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 7 31 theme JNK 1194:1196 arg1 activation 1198:1207 JNK activation 1194:1207 JNK activation 1194:1207 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 4 32 theme underling 700:708 arg1 mechanisms 710:719 the underling mechanisms 696:719 the underling mechanisms 696:719 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 7 33 theme breast 1400:1405 arg1 TNBC 1415:1418 TNBC 1415:1418 TNBC 1415:1418 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 7 33 theme breast 1400:1405 arg1 cancer 1407:1412 triple-negative breast cancer 1384:1412 triple-negative breast cancer (TNBC) 1384:1419 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 3 34 theme transforming 419:430 arg1 mediator 480:487 a crucial mediator 470:487 a crucial mediator in the interaction of cancer cells with TME 470:531 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 3 34 theme transforming 419:430 arg1 expression 458:467 transforming growth factor-β1 (TGF-β1) expression 419:467 transforming growth factor-β1 (TGF-β1) expression 419:467 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 0 35 theme Chondroitin 0:10 arg1 factor 25:30 Chondroitin polymerizing factor 0:30 Chondroitin polymerizing factor 0:30 Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation. 36042157 7 36 theme BRCA 1113:1116 arg1 proliferation 1123:1135 BRCA cell proliferation 1113:1135 BRCA cell proliferation 1113:1135 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 7 37 dep promotes 1104:1111 arg1 remove 1264:1269 remove 1264:1269 can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC) 1260:1419 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 3 38 from mediator 480:487 arg1 interaction 496:506 the interaction 492:506 the interaction of cancer cells with TME 492:531 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 7 39 theme MDA-MB-231 1344:1353 arg1 cells 1355:1359 MDA-MB-231 cells 1344:1359 MDA-MB-231 cells 1344:1359 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 3 40 theme growth 432:437 arg1 mediator 480:487 a crucial mediator 470:487 a crucial mediator in the interaction of cancer cells with TME 470:531 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 3 40 theme growth 432:437 arg1 expression 458:467 transforming growth factor-β1 (TGF-β1) expression 419:467 transforming growth factor-β1 (TGF-β1) expression 419:467 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 7 41 theme cell 1118:1121 arg1 proliferation 1123:1135 BRCA cell proliferation 1113:1135 BRCA cell proliferation 1113:1135 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 0 42 theme JNK 131:133 arg1 activation 140:149 the upstream TGF-β1/SMAD3 and JNK axis activation 101:149 activation 140:149 Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation. 36042157 9 43 theme upstream 1570:1577 arg1 signaling 1595:1603 the upstream of JNK or SMAD3 signaling 1566:1603 the upstream of JNK or SMAD3 signaling 1566:1603 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 7 44 from proliferation 1303:1315 arg1 cells 1355:1359 MDA-MB-231 cells 1344:1359 MDA-MB-231 cells 1344:1359 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 4 45 theme clinicopathological 609:627 arg1 features 629:636 the clinicopathological features 605:636 the clinicopathological features of breast cancer (BRCA) 605:660 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 6 46 theme CHPF 917:920 arg1 high-expression 898:912 The high-expression 894:912 The high-expression of CHPF 894:920 The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. 36042157 7 47 from migration 1318:1326 arg1 cells 1355:1359 MDA-MB-231 cells 1344:1359 MDA-MB-231 cells 1344:1359 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 6 48 theme lymph 994:998 arg1 metastasis 1005:1014 lymph node metastasis 994:1014 lymph node metastasis 994:1014 The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. 36042157 0 49 theme poor 43:46 arg1 prognosis 48:56 a poor prognosis 41:56 a poor prognosis 41:56 Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation. 36042157 9 50 theme novel 1619:1623 arg1 target 1637:1642 a novel therapeutic target 1617:1642 a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression 1617:1706 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 5 51 theme human 806:810 arg1 tissues 817:823 human BRCA tissues 806:823 human BRCA tissues 806:823 We found that CHPF expression is significantly increased in human BRCA tissues, and it is positively associated with TGF-β expression (r = 0.7125). 36042157 1 52 theme tumor 191:195 arg1 TME 215:217 TME 215:217 TME 215:217 Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. 36042157 1 52 theme tumor 191:195 arg1 microenvironment 197:212 the tumor microenvironment 187:212 the tumor microenvironment (TME) 187:218 Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. 36042157 3 53 theme TGF-β1 450:455 arg1 mediator 480:487 a crucial mediator 470:487 a crucial mediator in the interaction of cancer cells with TME 470:531 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 3 53 theme TGF-β1 450:455 arg1 expression 458:467 transforming growth factor-β1 (TGF-β1) expression 419:467 transforming growth factor-β1 (TGF-β1) expression 419:467 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 3 54 theme factor-β1 439:447 arg1 mediator 480:487 a crucial mediator 470:487 a crucial mediator in the interaction of cancer cells with TME 470:531 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 3 54 theme factor-β1 439:447 arg1 expression 458:467 transforming growth factor-β1 (TGF-β1) expression 419:467 transforming growth factor-β1 (TGF-β1) expression 419:467 It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. 36042157 0 55 theme axis 135:138 arg1 activation 140:149 the upstream TGF-β1/SMAD3 and JNK axis activation 101:149 activation 140:149 Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation. 36042157 8 56 dep suggested 1448:1456 arg1 function 1467:1474 function 1467:1474 may function as an oncogene 1463:1489 Collectively, our finding suggested CHPF may function as an oncogene and is highly expressed in human BRCA tissues. 36042157 8 56 dep suggested 1448:1456 arg1 expressed 1505:1513 expressed 1505:1513 is highly expressed in human BRCA tissues 1495:1535 Collectively, our finding suggested CHPF may function as an oncogene and is highly expressed in human BRCA tissues. 36042157 5 57 theme BRCA 812:815 arg1 tissues 817:823 human BRCA tissues 806:823 human BRCA tissues 806:823 We found that CHPF expression is significantly increased in human BRCA tissues, and it is positively associated with TGF-β expression (r = 0.7125). 36042157 4 58 with mechanisms 710:719 arg1 features 629:636 the clinicopathological features 605:636 the clinicopathological features of breast cancer (BRCA) 605:660 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 7 59 attach derived 1371:1377 arg1 TNBC 1415:1418 TNBC 1415:1418 TNBC 1415:1418 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 7 59 attach derived 1371:1377 arg2 cells 1355:1359 MDA-MB-231 cells 1344:1359 MDA-MB-231 cells 1344:1359 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 7 59 attach derived 1371:1377 arg1 cancer 1407:1412 triple-negative breast cancer 1384:1412 triple-negative breast cancer (TNBC) 1384:1419 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 7 60 theme cell 1298:1301 arg1 proliferation 1303:1315 cell proliferation 1298:1315 cell proliferation 1298:1315 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 4 61 theme oncogenic 675:683 arg1 effect 685:690 the oncogenic effect 671:690 the oncogenic effect 671:690 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 9 62 theme JNK 1582:1584 arg1 upstream 1570:1577 upstream 1570:1577 upstream 1570:1577 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 8 63 theme human 1518:1522 arg1 tissues 1529:1535 human BRCA tissues 1518:1535 human BRCA tissues 1518:1535 Collectively, our finding suggested CHPF may function as an oncogene and is highly expressed in human BRCA tissues. 36042157 7 64 theme JNK 1219:1221 arg1 inhibitor 1250:1258 JNK (SP600125) or SMAD3 (SIS3) inhibitor 1219:1258 JNK (SP600125) or SMAD3 (SIS3) inhibitor 1219:1258 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 9 65 theme refractory 1648:1657 arg1 patients 1664:1671 refractory TNBC patients 1648:1671 refractory TNBC patients with CHPF abnormal high-expression 1648:1706 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 4 66 with association 569:579 arg1 features 629:636 the clinicopathological features 605:636 the clinicopathological features of breast cancer (BRCA) 605:660 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 2 67 theme Chondroitin 269:279 arg1 CHPF 302:305 CHPF 302:305 CHPF 302:305 Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). 36042157 2 67 theme Chondroitin 269:279 arg1 factor 294:299 Chondroitin polymerizing factor 269:299 Chondroitin polymerizing factor (CHPF) 269:306 Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). 36042157 2 67 theme Chondroitin 269:279 arg1 glycosyltransferase 313:331 a glycosyltransferase 311:331 a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS) 311:391 Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). 36042157 7 68 from invasion 1332:1339 arg1 cells 1355:1359 MDA-MB-231 cells 1344:1359 MDA-MB-231 cells 1344:1359 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 4 69 theme CHPF 584:587 arg1 expression 589:598 CHPF expression 584:598 CHPF expression 584:598 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 4 70 theme BRCA 734:737 arg1 cells 739:743 BRCA cells 734:743 BRCA cells 734:743 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 7 71 theme CHPF 1288:1291 arg1 promotion 1275:1283 the promotion 1271:1283 the promotion of CHPF 1271:1291 The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). 36042157 1 72 theme Aberrant 152:159 arg1 composition 161:171 Aberrant composition 152:171 Aberrant composition of glycans in the tumor microenvironment (TME) 152:218 Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. 36042157 0 73 theme breast 71:76 arg1 progression 85:95 breast cancer progression 71:95 breast cancer progression 71:95 Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation. 36042157 9 74 with patients 1664:1671 arg1 high-expression 1692:1706 CHPF abnormal high-expression 1678:1706 CHPF abnormal high-expression 1678:1706 Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression. 36042157 6 75 theme node 1000:1003 arg1 metastasis 1005:1014 lymph node metastasis 994:1014 lymph node metastasis 994:1014 The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. 36042157 6 76 theme clinical 1017:1024 arg1 staging 1026:1032 clinical staging 1017:1032 clinical staging 1017:1032 The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. 36042157 1 77 theme tumor 235:239 arg1 progression 241:251 tumor progression 235:251 tumor progression 235:251 Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. 36042157 8 78 theme BRCA 1524:1527 arg1 tissues 1529:1535 human BRCA tissues 1518:1535 human BRCA tissues 1518:1535 Collectively, our finding suggested CHPF may function as an oncogene and is highly expressed in human BRCA tissues. 36042157 2 79 theme sulfate 380:386 arg1 biosynthesis 352:363 the biosynthesis 348:363 the biosynthesis of chondroitin sulfate (CS) 348:391 Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). 36042157 4 80 theme expression 589:598 arg1 mechanisms 710:719 the underling mechanisms 696:719 the underling mechanisms 696:719 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 4 80 theme expression 589:598 arg1 association 569:579 the association 565:579 the association of CHPF expression with the clinicopathological features of breast cancer (BRCA) 565:660 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 36042157 4 80 theme expression 589:598 arg1 effect 685:690 the oncogenic effect 671:690 the oncogenic effect 671:690 In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. 35353877 4 0 theme S. 561:562 arg1 sequences 582:590 >300 S. marcescens genome sequences 556:590 >300 S. marcescens genome sequences 556:590 Capsule loci (KL) were extracted from >300 S. marcescens genome sequences and compared. 35353877 5 1 theme sequences 638:646 arg1 comparison 621:630 A phylogenetic comparison 606:630 A phylogenetic comparison of KL sequences 606:646 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 10 2 theme KL1 1452:1454 arg1 investigation 1435:1447 Further investigation 1427:1447 Further investigation of KL1 and KL2 sequences 1427:1472 Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. 35353877 3 3 theme marcescens 497:506 arg1 isolates 508:515 S. marcescens isolates 494:515 S. marcescens isolates 494:515 In this study, we determined the degree of capsule genetic diversity among S. marcescens isolates. 35353877 10 4 dep KL1 1452:1454 arg1 sequences 1464:1472 sequences 1464:1472 sequences 1464:1472 Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. 35353877 2 5 from survival 341:348 arg1 serum 412:416 human serum 406:416 human serum 406:416 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 2 5 from survival 341:348 arg1 model 379:383 a murine model 370:383 a murine model of bacteremia 370:397 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 4 6 theme genome 575:580 arg1 sequences 582:590 >300 S. marcescens genome sequences 556:590 >300 S. marcescens genome sequences 556:590 Capsule loci (KL) were extracted from >300 S. marcescens genome sequences and compared. 35353877 13 7 theme infection-associated 1983:2002 arg1 clades 2004:2009 infection-associated clades 1983:2009 infection-associated clades with sialic acid CPS components 1983:2041 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 13 8 theme CPS 2028:2030 arg1 components 2032:2041 sialic acid CPS components 2016:2041 sialic acid CPS components 2016:2041 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 9 9 from KL2 1276:1278 arg1 strains 1255:1261 Bacteremia strains 1244:1261 Bacteremia strains from KL1 and KL2 1244:1278 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 12 10 theme monocytic 1796:1804 arg1 line 1811:1814 a human monocytic cell line 1788:1814 a human monocytic cell line 1788:1814 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 5 11 theme phylogenetic 608:619 arg1 comparison 621:630 A phylogenetic comparison 606:630 A phylogenetic comparison of KL sequences 606:646 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 1 12 theme infections 183:192 arg1 infections 183:192 infections 183:192 infections 183:192 Serratia marcescens is a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia. 35353877 1 12 theme infections 183:192 arg1 bacteremia 205:214 bacteremia 205:214 bacteremia 205:214 Serratia marcescens is a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia. 35353877 1 12 theme infections 183:192 arg1 variety 172:178 a variety 170:178 a variety of infections, including bacteremia 170:214 Serratia marcescens is a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia. 35353877 6 13 theme KL 880:881 arg1 types 883:887 the identified KL types 865:887 the identified KL types 865:887 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 6 14 from five 857:860 arg1 Strains 844:850 Strains 844:850 Strains from five of the identified KL types 844:887 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 10 15 theme KL2 1460:1462 arg1 investigation 1435:1447 Further investigation 1427:1447 Further investigation of KL1 and KL2 sequences 1427:1472 Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. 35353877 13 16 theme sialic 2016:2021 arg1 components 2032:2041 sialic acid CPS components 2016:2041 sialic acid CPS components 2016:2041 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 6 17 theme CPS 962:964 arg1 study 915:919 further study 907:919 further study 907:919 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 6 17 theme CPS 962:964 arg1 analysis 941:948 electrophoretic analysis 925:948 electrophoretic analysis 925:948 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 7 18 theme constituent 1094:1104 arg1 monosaccharides 1106:1120 the constituent monosaccharides 1090:1120 the constituent monosaccharides for each strain 1090:1136 Polysaccharide composition analysis confirmed this observation and identified the constituent monosaccharides for each strain. 35353877 4 19 dep S. 561:562 arg1 marcescens 564:573 marcescens 564:573 marcescens 564:573 Capsule loci (KL) were extracted from >300 S. marcescens genome sequences and compared. 35353877 9 20 from KL1 1268:1270 arg1 strains 1255:1261 Bacteremia strains 1244:1261 Bacteremia strains from KL1 and KL2 1244:1278 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 7 21 theme Polysaccharide 1012:1025 arg1 analysis 1039:1046 Polysaccharide composition analysis 1012:1046 Polysaccharide composition analysis 1012:1046 Polysaccharide composition analysis confirmed this observation and identified the constituent monosaccharides for each strain. 35353877 1 22 theme opportunistic 132:144 arg1 pathogen 146:153 a versatile opportunistic pathogen 120:153 a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia 120:214 Serratia marcescens is a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia. 35353877 1 22 theme opportunistic 132:144 arg1 marcescens 106:115 Serratia marcescens 97:115 Serratia marcescens 97:115 Serratia marcescens is a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia. 35353877 6 23 theme electrophoretic 925:939 arg1 analysis 941:948 electrophoretic analysis 925:948 electrophoretic analysis 925:948 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 5 24 theme KL 684:685 arg1 diversity 687:695 KL diversity 684:695 KL diversity within S. marcescens as a species 684:729 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 12 25 theme increased 1741:1749 arg1 susceptibility 1751:1764 increased susceptibility 1741:1764 increased susceptibility to internalization by a human monocytic cell line 1741:1814 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 5 26 theme strong 737:742 arg1 delineation 744:754 a strong delineation 735:754 a strong delineation between KL sequences originating from infection isolates versus environmental isolates 735:841 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 9 27 theme N-acetylneuraminic 1335:1352 arg1 acid 1354:1357 N-acetylneuraminic acid 1335:1357 N-acetylneuraminic acid 1335:1357 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 5 28 theme environmental 820:832 arg1 isolates 834:841 environmental isolates 820:841 environmental isolates 820:841 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 13 29 theme capsule 1926:1932 arg1 repertoire 1942:1951 the capsule genetic repertoire 1922:1951 the capsule genetic repertoire of S. marcescens 1922:1968 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 13 29 theme capsule 1926:1932 arg1 marcescens 1959:1968 S. marcescens 1956:1968 S. marcescens 1956:1968 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 12 30 theme production 1718:1727 arg1 absence 1687:1693 The absence 1683:1693 The absence of sialic acid and CPS production 1683:1727 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 6 31 theme glycans 1003:1009 arg1 production 980:989 the production 976:989 the production of distinct glycans 976:1009 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 9 32 theme sialic 1364:1369 arg1 acids 1371:1375 two sialic acids 1360:1375 two sialic acids that were not found in strains from other clades 1360:1424 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 9 32 theme sialic 1364:1369 arg1 acid 1326:1329 ketodeoxynonulonic acid 1307:1329 ketodeoxynonulonic acid 1307:1329 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 12 33 theme sialic 1698:1703 arg1 acid 1705:1708 sialic acid 1698:1708 sialic acid 1698:1708 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 2 34 theme bacteremia 388:397 arg1 model 379:383 a murine model 370:383 a murine model of bacteremia 370:397 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 10 35 theme Further 1427:1433 arg1 investigation 1435:1447 Further investigation 1427:1447 Further investigation of KL1 and KL2 sequences 1427:1472 Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. 35353877 0 36 theme distinct 18:25 arg1 types 35:39 distinct capsule types 18:39 distinct capsule types 18:39 Identification of distinct capsule types associated with Serratia marcescens infection isolates. 35353877 6 37 theme identified 869:878 arg1 types 883:887 the identified KL types 865:887 the identified KL types 865:887 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 12 38 dep S. 1836:1837 arg1 marcescens 1839:1848 marcescens 1839:1848 marcescens 1839:1848 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 0 39 theme types 35:39 arg1 Identification 0:13 Identification 0:13 Identification of distinct capsule types 0:39 Identification of distinct capsule types associated with Serratia marcescens infection isolates. 35353877 4 40 theme Capsule 518:524 arg1 KL 532:533 KL 532:533 KL 532:533 Capsule loci (KL) were extracted from >300 S. marcescens genome sequences and compared. 35353877 4 40 theme Capsule 518:524 arg1 loci 526:529 Capsule loci 518:529 Capsule loci (KL) 518:534 Capsule loci (KL) were extracted from >300 S. marcescens genome sequences and compared. 35353877 10 41 theme biosynthesis 1567:1578 arg1 functions 1580:1588 sialic acid biosynthesis functions 1555:1588 sialic acid biosynthesis functions 1555:1588 Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. 35353877 10 41 theme biosynthesis 1567:1578 arg1 genes 1489:1493 two genes 1485:1493 two genes 1485:1493 Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. 35353877 2 42 theme marcescens 356:365 arg1 survival 341:348 the survival 337:348 the survival of S. marcescens in a murine model of bacteremia and in human serum 337:416 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 8 43 theme predominant 1143:1153 arg1 clades 1176:1181 Two predominant infection-associated clades 1139:1181 Two predominant infection-associated clades 1139:1181 Two predominant infection-associated clades, designated KL1 and KL2, emerged from the capsule phylogeny. 35353877 2 44 theme capsule 256:262 arg1 biosynthesis 285:296 capsule polysaccharide (CPS) biosynthesis 256:296 capsule polysaccharide (CPS) biosynthesis 256:296 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 10 45 theme sialic 1555:1560 arg1 functions 1580:1588 sialic acid biosynthesis functions 1555:1588 sialic acid biosynthesis functions 1555:1588 Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. 35353877 10 45 theme sialic 1555:1560 arg1 genes 1489:1493 two genes 1485:1493 two genes 1485:1493 Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. 35353877 3 46 theme capsule 462:468 arg1 diversity 478:486 capsule genetic diversity 462:486 capsule genetic diversity among S. marcescens isolates 462:515 In this study, we determined the degree of capsule genetic diversity among S. marcescens isolates. 35353877 11 47 theme acid 1658:1661 arg1 loss 1643:1646 the loss 1639:1646 the loss of sialic acid and CPS production 1639:1680 Disruption of neuB in a KL1 isolate resulted in the loss of sialic acid and CPS production. 35353877 5 48 theme KL 635:636 arg1 sequences 638:646 KL sequences 635:646 KL sequences 635:646 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 3 49 theme S. 494:495 arg1 isolates 508:515 S. marcescens isolates 494:515 S. marcescens isolates 494:515 In this study, we determined the degree of capsule genetic diversity among S. marcescens isolates. 35353877 6 50 theme further 907:913 arg1 study 915:919 further study 907:919 further study 907:919 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 12 51 theme human 1790:1794 arg1 line 1811:1814 a human monocytic cell line 1788:1814 a human monocytic cell line 1788:1814 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 11 52 theme CPS 1667:1669 arg1 production 1671:1680 CPS production 1667:1680 CPS production 1667:1680 Disruption of neuB in a KL1 isolate resulted in the loss of sialic acid and CPS production. 35353877 13 53 theme acid 2023:2026 arg1 components 2032:2041 sialic acid CPS components 2016:2041 sialic acid CPS components 2016:2041 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 2 54 theme translocation 302:314 arg1 locus 316:320 the capsule polysaccharide (CPS) biosynthesis and translocation locus 252:320 the capsule polysaccharide (CPS) biosynthesis and translocation locus 252:320 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 12 55 theme cell 1806:1809 arg1 line 1811:1814 a human monocytic cell line 1788:1814 a human monocytic cell line 1788:1814 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 3 56 theme diversity 478:486 arg1 degree 452:457 the degree 448:457 the degree of capsule genetic diversity among S. marcescens isolates 448:515 In this study, we determined the degree of capsule genetic diversity among S. marcescens isolates. 35353877 9 57 theme Bacteremia 1244:1253 arg1 strains 1255:1261 Bacteremia strains 1244:1261 Bacteremia strains from KL1 and KL2 1244:1278 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 2 58 theme biosynthesis 285:296 arg1 locus 316:320 the capsule polysaccharide (CPS) biosynthesis and translocation locus 252:320 the capsule polysaccharide (CPS) biosynthesis and translocation locus 252:320 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 6 59 theme types 883:887 arg1 types 883:887 the identified KL types 865:887 the identified KL types 865:887 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 6 59 theme types 883:887 arg1 five 857:860 five 857:860 five 857:860 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 11 60 theme KL1 1615:1617 arg1 isolate 1619:1625 a KL1 isolate 1613:1625 a KL1 isolate 1613:1625 Disruption of neuB in a KL1 isolate resulted in the loss of sialic acid and CPS production. 35353877 8 61 theme capsule 1225:1231 arg1 phylogeny 1233:1241 the capsule phylogeny 1221:1241 the capsule phylogeny 1221:1241 Two predominant infection-associated clades, designated KL1 and KL2, emerged from the capsule phylogeny. 35353877 11 62 theme neuB 1605:1608 arg1 Disruption 1591:1600 Disruption 1591:1600 Disruption of neuB in a KL1 isolate 1591:1625 Disruption of neuB in a KL1 isolate resulted in the loss of sialic acid and CPS production. 35353877 5 63 theme diversity 687:695 arg1 delineation 744:754 a strong delineation 735:754 a strong delineation between KL sequences originating from infection isolates versus environmental isolates 735:841 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 5 63 theme diversity 687:695 arg1 level 675:679 a substantial level 661:679 a substantial level of KL diversity within S. marcescens as a species 661:729 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 6 64 theme purified 953:960 arg1 CPS 962:964 purified CPS 953:964 purified CPS indicated the production of distinct glycans 953:1009 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 9 65 located found 1391:1395 arg2 acids 1371:1375 two sialic acids 1360:1375 two sialic acids that were not found in strains from other clades 1360:1424 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 9 65 located found 1391:1395 arg1 strains 1400:1406 strains 1400:1406 strains from other clades 1400:1424 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 9 65 located found 1391:1395 arg2 acid 1326:1329 ketodeoxynonulonic acid 1307:1329 ketodeoxynonulonic acid 1307:1329 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 5 66 theme substantial 663:673 arg1 level 675:679 a substantial level 661:679 a substantial level of KL diversity within S. marcescens as a species 661:729 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 1 67 theme versatile 122:130 arg1 pathogen 146:153 a versatile opportunistic pathogen 120:153 a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia 120:214 Serratia marcescens is a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia. 35353877 1 67 theme versatile 122:130 arg1 marcescens 106:115 Serratia marcescens 97:115 Serratia marcescens 97:115 Serratia marcescens is a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia. 35353877 9 68 theme ketodeoxynonulonic 1307:1324 arg1 acids 1371:1375 two sialic acids 1360:1375 two sialic acids that were not found in strains from other clades 1360:1424 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 9 68 theme ketodeoxynonulonic 1307:1324 arg1 acid 1326:1329 ketodeoxynonulonic acid 1307:1329 ketodeoxynonulonic acid 1307:1329 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 2 69 theme CPS 280:282 arg1 biosynthesis 285:296 capsule polysaccharide (CPS) biosynthesis 256:296 capsule polysaccharide (CPS) biosynthesis 256:296 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 7 70 theme composition 1027:1037 arg1 analysis 1039:1046 Polysaccharide composition analysis 1012:1046 Polysaccharide composition analysis 1012:1046 Polysaccharide composition analysis confirmed this observation and identified the constituent monosaccharides for each strain. 35353877 13 71 theme marcescens 1959:1968 arg1 repertoire 1942:1951 the capsule genetic repertoire 1922:1951 the capsule genetic repertoire of S. marcescens 1922:1968 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 13 71 theme marcescens 1959:1968 arg1 marcescens 1959:1968 S. marcescens 1956:1968 S. marcescens 1956:1968 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 0 72 theme infection 77:85 arg1 isolates 87:94 Serratia marcescens infection isolates 57:94 Serratia marcescens infection isolates 57:94 Identification of distinct capsule types associated with Serratia marcescens infection isolates. 35353877 2 73 theme polysaccharide 264:277 arg1 biosynthesis 285:296 capsule polysaccharide (CPS) biosynthesis 256:296 capsule polysaccharide (CPS) biosynthesis 256:296 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 9 74 from clades 1419:1424 arg1 strains 1400:1406 strains 1400:1406 strains from other clades 1400:1424 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 11 75 from Disruption 1591:1600 arg1 isolate 1619:1625 a KL1 isolate 1613:1625 a KL1 isolate 1613:1625 Disruption of neuB in a KL1 isolate resulted in the loss of sialic acid and CPS production. 35353877 12 76 theme acid 1705:1708 arg1 absence 1687:1693 The absence 1683:1693 The absence of sialic acid and CPS production 1683:1727 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 13 77 theme genetic 1934:1940 arg1 repertoire 1942:1951 the capsule genetic repertoire 1922:1951 the capsule genetic repertoire of S. marcescens 1922:1968 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 13 77 theme genetic 1934:1940 arg1 marcescens 1959:1968 S. marcescens 1956:1968 S. marcescens 1956:1968 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 12 78 theme CPS 1714:1716 arg1 production 1718:1727 CPS production 1714:1727 CPS production 1714:1727 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 6 79 theme distinct 994:1001 arg1 glycans 1003:1009 distinct glycans 994:1009 distinct glycans 994:1009 Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. 35353877 5 80 theme infection 794:802 arg1 isolates 804:811 infection isolates 794:811 infection isolates 794:811 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 13 81 with clades 2004:2009 arg1 components 2032:2041 sialic acid CPS components 2016:2041 sialic acid CPS components 2016:2041 Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components. 35353877 0 82 theme capsule 27:33 arg1 types 35:39 distinct capsule types 18:39 distinct capsule types 18:39 Identification of distinct capsule types associated with Serratia marcescens infection isolates. 35353877 5 83 theme KL 764:765 arg1 sequences 767:775 KL sequences 764:775 KL sequences originating from infection isolates versus environmental isolates 764:841 A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. 35353877 0 84 dep Serratia 57:64 arg1 marcescens 66:75 marcescens 66:75 marcescens 66:75 Identification of distinct capsule types associated with Serratia marcescens infection isolates. 35353877 2 85 theme human 406:410 arg1 serum 412:416 human serum 406:416 human serum 406:416 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 0 86 theme Serratia 57:64 arg1 isolates 87:94 Serratia marcescens infection isolates 57:94 Serratia marcescens infection isolates 57:94 Identification of distinct capsule types associated with Serratia marcescens infection isolates. 35353877 9 87 theme other 1413:1417 arg1 clades 1419:1424 other clades 1413:1424 other clades 1413:1424 Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. 35353877 8 88 theme infection-associated 1155:1174 arg1 clades 1176:1181 Two predominant infection-associated clades 1139:1181 Two predominant infection-associated clades 1139:1181 Two predominant infection-associated clades, designated KL1 and KL2, emerged from the capsule phylogeny. 35353877 12 89 theme S. 1836:1837 arg1 resistance 1863:1872 S. marcescens phagocytosis resistance 1836:1872 S. marcescens phagocytosis resistance 1836:1872 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 10 90 theme acid 1562:1565 arg1 functions 1580:1588 sialic acid biosynthesis functions 1555:1588 sialic acid biosynthesis functions 1555:1588 Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. 35353877 10 90 theme acid 1562:1565 arg1 genes 1489:1493 two genes 1485:1493 two genes 1485:1493 Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. 35353877 2 91 theme previous 221:228 arg1 work 230:233 Our previous work 217:233 Our previous work 217:233 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35353877 12 92 theme phagocytosis 1850:1861 arg1 resistance 1863:1872 S. marcescens phagocytosis resistance 1836:1872 S. marcescens phagocytosis resistance 1836:1872 The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. 35353877 11 93 theme sialic 1651:1656 arg1 acid 1658:1661 sialic acid 1651:1661 sialic acid 1651:1661 Disruption of neuB in a KL1 isolate resulted in the loss of sialic acid and CPS production. 35353877 3 94 theme genetic 470:476 arg1 diversity 478:486 capsule genetic diversity 462:486 capsule genetic diversity among S. marcescens isolates 462:515 In this study, we determined the degree of capsule genetic diversity among S. marcescens isolates. 35353877 11 95 theme production 1671:1680 arg1 loss 1643:1646 the loss 1639:1646 the loss of sialic acid and CPS production 1639:1680 Disruption of neuB in a KL1 isolate resulted in the loss of sialic acid and CPS production. 35353877 2 96 theme murine 372:377 arg1 model 379:383 a murine model 370:383 a murine model of bacteremia 370:397 Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. 35472695 6 0 theme pathway 875:881 arg1 proteins 848:855 Four key proteins 839:855 Four key proteins of the glycolysis pathway 839:881 Four key proteins of the glycolysis pathway were detected with the immunochemistry method. 35472695 9 1 theme expressed 1174:1182 arg1 DEFs 1191:1194 DEFs 1191:1194 DEFs 1191:1194 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 9 1 theme expressed 1174:1182 arg1 flora 1184:1188 differentially expressed flora 1159:1188 differentially expressed flora (DEFs) 1159:1195 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 10 2 dep regulated 1402:1410 arg1 whereas 1451:1457 whereas 1451:1457 whereas 1451:1457 Cer was mainly regulated by Staphylococcus and Corynebacterium, whereas TG and DG were mainly regulated by Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 13 3 theme acne 1792:1795 arg1 rats 1797:1800 acne rats 1792:1800 acne rats 1792:1800 CONCLUSION CPT might help acne rats rebuild their skin microbiota and alter lipid metabolism signatures. 35472695 9 4 theme skin 1106:1109 arg1 microbiome 1111:1120 the skin microbiome 1102:1120 the skin microbiome 1102:1120 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 3 5 theme acne 477:480 arg1 therapy 482:488 acne therapy 477:488 acne therapy 477:488 Till date, only a few studies are directed to the impact of acne therapy on skin microbiota and lipid metabolites. 35472695 5 6 theme profiles 822:829 arg1 levels 831:836 lipid metabolites profiles levels 804:836 lipid metabolites profiles levels 804:836 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 13 7 theme CONCLUSION 1766:1775 arg1 CPT 1777:1779 CONCLUSION CPT 1766:1779 CONCLUSION CPT 1766:1779 CONCLUSION CPT might help acne rats rebuild their skin microbiota and alter lipid metabolism signatures. 35472695 3 8 theme lipid 513:517 arg1 metabolites 519:529 lipid metabolites 513:529 lipid metabolites 513:529 Till date, only a few studies are directed to the impact of acne therapy on skin microbiota and lipid metabolites. 35472695 1 9 theme prevalent 182:190 arg1 disorders 197:205 the most prevalent skin disorders 173:205 the most prevalent skin disorders 173:205 BACKGROUND Acne has become one of the most prevalent skin disorders, affecting mostly young people's physical and mental health globally. 35472695 0 10 theme acne 129:132 arg1 rat 134:136 the acne rat 125:136 the acne rat 125:136 Skin microbiome reconstruction and lipid metabolism profile alteration reveal the treatment mechanism of Cryptotanshinone in the acne rat. 35472695 9 11 theme expressed 1220:1228 arg1 metabolites 1236:1246 782 differentially expressed lipid metabolites 1201:1246 782 differentially expressed lipid metabolites (DELMs) 1201:1254 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 9 11 theme expressed 1220:1228 arg1 DELMs 1249:1253 DELMs 1249:1253 DELMs 1249:1253 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 1 12 theme disorders 197:205 arg1 disorders 197:205 the most prevalent skin disorders 173:205 the most prevalent skin disorders 173:205 BACKGROUND Acne has become one of the most prevalent skin disorders, affecting mostly young people's physical and mental health globally. 35472695 1 12 theme disorders 197:205 arg1 one 166:168 one 166:168 one 166:168 BACKGROUND Acne has become one of the most prevalent skin disorders, affecting mostly young people's physical and mental health globally. 35472695 9 13 theme metabolites 1236:1246 arg1 types 1150:1154 29 types 1147:1154 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) 1147:1254 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 5 14 theme lipid 804:808 arg1 levels 831:836 lipid metabolites profiles levels 804:836 lipid metabolites profiles levels 804:836 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 7 15 theme CPT 974:976 arg1 treatment 978:986 CPT treatment 974:986 CPT treatment of acne 974:994 Antibacterial analysis was used to evaluate CPT treatment of acne. 35472695 11 16 theme glycolysis 1557:1566 arg1 pathway 1568:1574 The glycolysis pathway 1553:1574 The glycolysis pathway 1553:1574 The glycolysis pathway was significantly regulated by Staphylococcus on CPT treatment of acne. 35472695 1 17 theme BACKGROUND 139:148 arg1 Acne 150:153 BACKGROUND Acne 139:153 BACKGROUND Acne 139:153 BACKGROUND Acne has become one of the most prevalent skin disorders, affecting mostly young people's physical and mental health globally. 35472695 5 18 dep METHODS 662:668 arg1 used 698:701 used 698:701 was used to detect skin microbiota composition, and absolute quantitative lipidomics 694:777 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 4 19 theme microbiome 622:631 arg1 integration 633:643 microbiome integration 622:643 microbiome integration with lipidomics 622:659 PURPOSE The action mechanism of CPT treatment of acne was investigated by the strategy of microbiome integration with lipidomics. 35472695 14 20 contain have 1931:1934 arg1 metabolites 1919:1929 skin lipid metabolites 1908:1929 skin lipid metabolites 1908:1929 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 14 20 contain have 1931:1934 arg1 microbes 1895:1902 skin microbes 1890:1902 skin microbes 1890:1902 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 14 20 contain have 1931:1934 arg2 correlation 1944:1954 a close correlation 1936:1954 a close correlation 1936:1954 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 7 21 used used 957:960 arg2 analysis 944:951 Antibacterial analysis 930:951 Antibacterial analysis 930:951 Antibacterial analysis was used to evaluate CPT treatment of acne. 35472695 0 22 theme treatment 82:90 arg1 mechanism 92:100 the treatment mechanism 78:100 the treatment mechanism of Cryptotanshinone 78:120 Skin microbiome reconstruction and lipid metabolism profile alteration reveal the treatment mechanism of Cryptotanshinone in the acne rat. 35472695 7 23 theme Antibacterial 930:942 arg1 analysis 944:951 Antibacterial analysis 930:951 Antibacterial analysis 930:951 Antibacterial analysis was used to evaluate CPT treatment of acne. 35472695 14 24 theme acne 2129:2132 arg1 development 2134:2144 acne development 2129:2144 acne development 2129:2144 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 5 25 theme DNA 679:681 arg1 sequencing 683:692 The 16Sr DNA sequencing 670:692 The 16Sr DNA sequencing 670:692 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 14 26 theme research 2022:2029 arg1 foundation 2031:2040 a research foundation 2020:2040 a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms 2020:2155 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 12 27 theme immune 1689:1694 arg1 system 1696:1701 immune system 1689:1701 immune system 1689:1701 The energy metabolism, lipid metabolism, immune system, glycan biosynthesis, and metabolism could be reversed by CPT. 35472695 2 28 theme acne 351:354 arg1 treatment 356:364 acne treatment 351:364 acne treatment 351:364 Cryptotanshinone (CPT) is a potential drug for acne, but its mechanism of acne treatment has not been thoroughly studied on the microbiota. 35472695 0 29 theme Skin 0:3 arg1 reconstruction 16:29 Skin microbiome reconstruction 0:29 Skin microbiome reconstruction 0:29 Skin microbiome reconstruction and lipid metabolism profile alteration reveal the treatment mechanism of Cryptotanshinone in the acne rat. 35472695 5 30 used used 698:701 arg2 sequencing 683:692 The 16Sr DNA sequencing 670:692 The 16Sr DNA sequencing 670:692 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 12 31 theme energy 1652:1657 arg1 metabolism 1659:1668 energy metabolism 1652:1668 energy metabolism 1652:1668 The energy metabolism, lipid metabolism, immune system, glycan biosynthesis, and metabolism could be reversed by CPT. 35472695 14 32 theme microbiome 2082:2091 arg1 imbalance 2093:2101 skin microbiome imbalance 2077:2101 skin microbiome imbalance 2077:2101 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 13 33 theme lipid 1842:1846 arg1 signatures 1859:1868 lipid metabolism signatures 1842:1868 lipid metabolism signatures 1842:1868 CONCLUSION CPT might help acne rats rebuild their skin microbiota and alter lipid metabolism signatures. 35472695 9 34 theme microbiome 1111:1120 arg1 Combination 1087:1097 Combination 1087:1097 Combination of the skin microbiome 1087:1120 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 9 34 theme microbiome 1111:1120 arg1 lipidomics 1126:1135 lipidomics 1126:1135 lipidomics 1126:1135 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 3 35 theme Till 417:420 arg1 date 422:425 Till date 417:425 Till date 417:425 Till date, only a few studies are directed to the impact of acne therapy on skin microbiota and lipid metabolites. 35472695 0 36 theme lipid 35:39 arg1 metabolism 41:50 lipid metabolism 35:50 lipid metabolism 35:50 Skin microbiome reconstruction and lipid metabolism profile alteration reveal the treatment mechanism of Cryptotanshinone in the acne rat. 35472695 9 37 dep Ralstonia 1328:1336 arg1 Corynebacterium 1311:1325 Corynebacterium 1311:1325 Corynebacterium 1311:1325 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 9 37 dep Ralstonia 1328:1336 arg1 Staphylococcus 1295:1308 Staphylococcus 1295:1308 Staphylococcus 1295:1308 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 11 38 theme CPT 1625:1627 arg1 treatment 1629:1637 CPT treatment 1625:1637 CPT treatment of acne 1625:1645 The glycolysis pathway was significantly regulated by Staphylococcus on CPT treatment of acne. 35472695 0 39 theme profile 52:58 arg1 alteration 60:69 profile alteration 52:69 profile alteration 52:69 Skin microbiome reconstruction and lipid metabolism profile alteration reveal the treatment mechanism of Cryptotanshinone in the acne rat. 35472695 5 40 used utilized 783:790 arg2 METHODS 662:668 METHODS 662:668 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics 662:777 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 0 41 dep reconstruction 16:29 arg1 alteration 60:69 profile alteration 52:69 profile alteration 52:69 Skin microbiome reconstruction and lipid metabolism profile alteration reveal the treatment mechanism of Cryptotanshinone in the acne rat. 35472695 4 42 theme action 544:549 arg1 mechanism 551:559 The action mechanism 540:559 PURPOSE The action mechanism of CPT treatment of acne 532:584 PURPOSE The action mechanism of CPT treatment of acne was investigated by the strategy of microbiome integration with lipidomics. 35472695 14 43 theme close 1938:1942 arg1 correlation 1944:1954 a close correlation 1936:1954 a close correlation 1936:1954 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 1 44 theme physical 240:247 arg1 health 260:265 mostly young people's physical and mental health 218:265 mostly young people's physical and mental health 218:265 BACKGROUND Acne has become one of the most prevalent skin disorders, affecting mostly young people's physical and mental health globally. 35472695 6 45 theme glycolysis 864:873 arg1 pathway 875:881 the glycolysis pathway 860:881 the glycolysis pathway 860:881 Four key proteins of the glycolysis pathway were detected with the immunochemistry method. 35472695 9 46 theme flora 1184:1188 arg1 types 1150:1154 29 types 1147:1154 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) 1147:1254 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 3 47 theme therapy 482:488 arg1 impact 467:472 the impact 463:472 the impact of acne therapy on skin microbiota and lipid metabolites 463:529 Till date, only a few studies are directed to the impact of acne therapy on skin microbiota and lipid metabolites. 35472695 1 48 theme mental 253:258 arg1 health 260:265 mostly young people's physical and mental health 218:265 mostly young people's physical and mental health 218:265 BACKGROUND Acne has become one of the most prevalent skin disorders, affecting mostly young people's physical and mental health globally. 35472695 4 49 with integration 633:643 arg1 lipidomics 650:659 lipidomics 650:659 lipidomics 650:659 PURPOSE The action mechanism of CPT treatment of acne was investigated by the strategy of microbiome integration with lipidomics. 35472695 3 50 from impact 467:472 arg1 microbiota 498:507 skin microbiota 493:507 skin microbiota 493:507 Till date, only a few studies are directed to the impact of acne therapy on skin microbiota and lipid metabolites. 35472695 3 50 from impact 467:472 arg1 metabolites 519:529 lipid metabolites 513:529 lipid metabolites 513:529 Till date, only a few studies are directed to the impact of acne therapy on skin microbiota and lipid metabolites. 35472695 5 51 theme metabolites 810:820 arg1 levels 831:836 lipid metabolites profiles levels 804:836 lipid metabolites profiles levels 804:836 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 6 52 theme key 844:846 arg1 proteins 848:855 Four key proteins 839:855 Four key proteins of the glycolysis pathway 839:881 Four key proteins of the glycolysis pathway were detected with the immunochemistry method. 35472695 5 53 theme skin 713:716 arg1 composition 729:739 skin microbiota composition 713:739 skin microbiota composition 713:739 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 3 54 theme skin 493:496 arg1 microbiota 498:507 skin microbiota 493:507 skin microbiota 493:507 Till date, only a few studies are directed to the impact of acne therapy on skin microbiota and lipid metabolites. 35472695 1 55 theme skin 192:195 arg1 disorders 197:205 the most prevalent skin disorders 173:205 the most prevalent skin disorders 173:205 BACKGROUND Acne has become one of the most prevalent skin disorders, affecting mostly young people's physical and mental health globally. 35472695 4 56 theme treatment 568:576 arg1 PURPOSE 532:538 PURPOSE 532:538 PURPOSE The action mechanism of CPT treatment of acne 532:584 PURPOSE The action mechanism of CPT treatment of acne was investigated by the strategy of microbiome integration with lipidomics. 35472695 9 57 theme lipid 1230:1234 arg1 metabolites 1236:1246 782 differentially expressed lipid metabolites 1201:1246 782 differentially expressed lipid metabolites (DELMs) 1201:1254 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 9 57 theme lipid 1230:1234 arg1 DELMs 1249:1253 DELMs 1249:1253 DELMs 1249:1253 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 14 58 theme lipid 1913:1917 arg1 metabolites 1919:1929 skin lipid metabolites 1908:1929 skin lipid metabolites 1908:1929 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 6 59 theme immunochemistry 906:920 arg1 method 922:927 the immunochemistry method 902:927 the immunochemistry method 902:927 Four key proteins of the glycolysis pathway were detected with the immunochemistry method. 35472695 14 60 dep discovery 2050:2058 arg1 mechanisms 2146:2155 mechanisms 2146:2155 mechanisms 2146:2155 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 4 61 theme acne 581:584 arg1 treatment 568:576 CPT treatment 564:576 CPT treatment of acne 564:584 PURPOSE The action mechanism of CPT treatment of acne was investigated by the strategy of microbiome integration with lipidomics. 35472695 5 62 theme 16Sr 674:677 arg1 sequencing 683:692 The 16Sr DNA sequencing 670:692 The 16Sr DNA sequencing 670:692 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 7 63 theme acne 991:994 arg1 treatment 978:986 CPT treatment 974:986 CPT treatment of acne 974:994 Antibacterial analysis was used to evaluate CPT treatment of acne. 35472695 14 64 theme skin 1908:1911 arg1 metabolites 1919:1929 skin lipid metabolites 1908:1929 skin lipid metabolites 1908:1929 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 8 65 theme RESULTS 997:1003 arg1 CPT 1005:1007 RESULTS CPT 997:1007 RESULTS CPT 997:1007 RESULTS CPT significantly inhibited Staphylococcus epidermidis and Staphylococcus aureus. 35472695 14 66 theme development 2134:2144 arg1 discovery 2050:2058 the discovery 2046:2058 the discovery of biomarkers of skin microbiome imbalance 2046:2101 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 14 66 theme development 2134:2144 arg1 treatment 2116:2124 targeted treatment 2107:2124 targeted treatment of acne development 2107:2144 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 4 67 theme integration 633:643 arg1 strategy 610:617 the strategy 606:617 the strategy of microbiome integration with lipidomics 606:659 PURPOSE The action mechanism of CPT treatment of acne was investigated by the strategy of microbiome integration with lipidomics. 35472695 0 68 theme Cryptotanshinone 105:120 arg1 mechanism 92:100 the treatment mechanism 78:100 the treatment mechanism of Cryptotanshinone 78:120 Skin microbiome reconstruction and lipid metabolism profile alteration reveal the treatment mechanism of Cryptotanshinone in the acne rat. 35472695 12 69 theme glycan 1704:1709 arg1 biosynthesis 1711:1722 glycan biosynthesis 1704:1722 glycan biosynthesis 1704:1722 The energy metabolism, lipid metabolism, immune system, glycan biosynthesis, and metabolism could be reversed by CPT. 35472695 12 70 theme lipid 1671:1675 arg1 metabolism 1677:1686 lipid metabolism 1671:1686 lipid metabolism 1671:1686 The energy metabolism, lipid metabolism, immune system, glycan biosynthesis, and metabolism could be reversed by CPT. 35472695 14 71 theme targeted 2107:2114 arg1 treatment 2116:2124 targeted treatment 2107:2124 targeted treatment of acne development 2107:2144 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 2 72 theme treatment 356:364 arg1 mechanism 338:346 its mechanism 334:346 its mechanism of acne treatment 334:364 Cryptotanshinone (CPT) is a potential drug for acne, but its mechanism of acne treatment has not been thoroughly studied on the microbiota. 35472695 0 73 theme microbiome 5:14 arg1 reconstruction 16:29 Skin microbiome reconstruction 0:29 Skin microbiome reconstruction 0:29 Skin microbiome reconstruction and lipid metabolism profile alteration reveal the treatment mechanism of Cryptotanshinone in the acne rat. 35472695 14 74 theme imbalance 2093:2101 arg1 biomarkers 2063:2072 biomarkers 2063:2072 biomarkers of skin microbiome imbalance 2063:2101 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 4 75 dep PURPOSE 532:538 arg1 mechanism 551:559 The action mechanism 540:559 PURPOSE The action mechanism of CPT treatment of acne 532:584 PURPOSE The action mechanism of CPT treatment of acne was investigated by the strategy of microbiome integration with lipidomics. 35472695 5 76 theme quantitative 755:766 arg1 lipidomics 768:777 absolute quantitative lipidomics 746:777 absolute quantitative lipidomics 746:777 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 14 77 theme skin 2077:2080 arg1 imbalance 2093:2101 skin microbiome imbalance 2077:2101 skin microbiome imbalance 2077:2101 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 13 78 theme metabolism 1848:1857 arg1 signatures 1859:1868 lipid metabolism signatures 1842:1868 lipid metabolism signatures 1842:1868 CONCLUSION CPT might help acne rats rebuild their skin microbiota and alter lipid metabolism signatures. 35472695 5 79 theme microbiota 718:727 arg1 composition 729:739 skin microbiota composition 713:739 skin microbiota composition 713:739 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 35472695 14 80 theme biomarkers 2063:2072 arg1 discovery 2050:2058 the discovery 2046:2058 the discovery of biomarkers of skin microbiome imbalance 2046:2101 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 14 80 theme biomarkers 2063:2072 arg1 treatment 2116:2124 targeted treatment 2107:2124 targeted treatment of acne development 2107:2144 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 9 81 dep Combination 1087:1097 arg1 analysis 1137:1144 analysis 1137:1144 analysis 1137:1144 Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. 35472695 11 82 theme acne 1642:1645 arg1 treatment 1629:1637 CPT treatment 1625:1637 CPT treatment of acne 1625:1645 The glycolysis pathway was significantly regulated by Staphylococcus on CPT treatment of acne. 35472695 2 83 theme potential 305:313 arg1 Cryptotanshinone 277:292 Cryptotanshinone 277:292 Cryptotanshinone (CPT) 277:298 Cryptotanshinone (CPT) is a potential drug for acne, but its mechanism of acne treatment has not been thoroughly studied on the microbiota. 35472695 2 83 theme potential 305:313 arg1 drug 315:318 a potential drug 303:318 a potential drug for acne 303:327 Cryptotanshinone (CPT) is a potential drug for acne, but its mechanism of acne treatment has not been thoroughly studied on the microbiota. 35472695 1 84 theme young 225:229 arg1 people 231:236 young people's 225:238 young people's 225:238 BACKGROUND Acne has become one of the most prevalent skin disorders, affecting mostly young people's physical and mental health globally. 35472695 14 85 theme skin 1890:1893 arg1 microbes 1895:1902 skin microbes 1890:1902 skin microbes 1890:1902 Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms. 35472695 4 86 theme CPT 564:566 arg1 treatment 568:576 CPT treatment 564:576 CPT treatment of acne 564:584 PURPOSE The action mechanism of CPT treatment of acne was investigated by the strategy of microbiome integration with lipidomics. 35472695 13 87 theme skin 1816:1819 arg1 microbiota 1821:1830 their skin microbiota 1810:1830 their skin microbiota 1810:1830 CONCLUSION CPT might help acne rats rebuild their skin microbiota and alter lipid metabolism signatures. 35472695 5 88 theme absolute 746:753 arg1 lipidomics 768:777 absolute quantitative lipidomics 746:777 absolute quantitative lipidomics 746:777 METHODS The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. 36011367 4 0 theme dilated 918:924 arg1 cardiomyopathy 926:939 dilated cardiomyopathy 918:939 dilated cardiomyopathy 918:939 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 3 1 theme biological 577:586 arg1 binding 733:739 calcium ion binding 721:739 calcium ion binding 721:739 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 1 theme biological 577:586 arg1 processes 588:596 biological processes 577:596 biological processes 577:596 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 1 theme biological 577:586 arg1 binding 790:796 pyridoxal phosphate binding 770:796 pyridoxal phosphate binding 770:796 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 1 theme biological 577:586 arg1 binding 757:763 actin filament binding 742:763 actin filament binding 742:763 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 1 2 theme soluble 202:208 arg1 fiber 210:214 dietary soluble fiber 194:214 dietary soluble fiber from beet pulp (BP) 194:234 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 6 3 theme dietary 1267:1273 arg1 group 1278:1282 the dietary BP group 1263:1282 the dietary BP group 1263:1282 In contrast, the DEGs in the dietary BP group were related to intestinal epithelium integrity and immune response to pathogens, including S100A2, GCNT3, LYZ, SCGB1A1, SAA3, and ST3GAL1. 36011367 4 4 theme type 1018:1021 arg1 biosynthesis 1032:1043 mucin type O-glycan biosynthesis 1012:1043 mucin type O-glycan biosynthesis 1012:1043 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 1 5 from pulp 226:229 arg1 effects 183:189 the effects 179:189 the effects of dietary soluble fiber from beet pulp (BP) 179:234 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 5 from pulp 226:229 arg1 HS 171:172 HS 171:172 HS 171:172 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 5 from pulp 226:229 arg1 fiber 210:214 dietary soluble fiber 194:214 dietary soluble fiber from beet pulp (BP) 194:234 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 5 from pulp 226:229 arg1 stress 163:168 heat stress 158:168 heat stress (HS) 158:173 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 6 theme heat 158:161 arg1 HS 171:172 HS 171:172 HS 171:172 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 6 theme heat 158:161 arg1 stress 163:168 heat stress 158:168 heat stress (HS) 158:173 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 7 7 theme valuable 1536:1543 arg1 reference 1545:1553 a valuable reference 1534:1553 a valuable reference for future studies 1534:1572 These findings might help understand the HS response and the effect of dietary fiber (DF) regarding HS and be a valuable reference for future studies. 36011367 3 8 theme Z 625:625 arg1 disc 627:630 Z disc 625:630 Z disc 625:630 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 0 9 theme Beet 101:104 arg1 Pulp 106:109 Beet Pulp 101:109 Beet Pulp 101:109 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 3 10 theme enrichment 441:450 arg1 analysis 452:459 The gene ontology (GO) enrichment analysis 418:459 The gene ontology (GO) enrichment analysis 418:459 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 4 11 theme actin 992:996 arg1 cytoskeleton 998:1009 actin cytoskeleton 992:1009 actin cytoskeleton 992:1009 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 3 12 from processes 588:596 arg1 composition 689:699 cellular composition 680:699 cellular composition 680:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 5 13 from genes 1090:1094 arg1 group 1140:1144 the HS group 1133:1144 the HS group 1133:1144 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 1 14 theme jejunum 309:315 arg1 genes 281:285 differentially expressed genes 256:285 differentially expressed genes 256:285 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 14 theme jejunum 309:315 arg1 expression 244:253 gene expression 239:253 gene expression (differentially expressed genes, DEGs) of the porcine jejunum 239:315 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 3 15 from cytoplasm 599:607 arg1 composition 689:699 cellular composition 680:699 cellular composition 680:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 1 16 from stress 163:168 arg1 BP 232:233 BP 232:233 BP 232:233 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 16 from stress 163:168 arg1 pulp 226:229 beet pulp 221:229 beet pulp (BP) 221:234 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 3 17 dep ontology 427:434 arg1 GO 437:438 GO 437:438 GO 437:438 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 18 theme ion 729:731 arg1 binding 733:739 calcium ion binding 721:739 calcium ion binding 721:739 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 18 theme ion 729:731 arg1 processes 588:596 biological processes 577:596 biological processes 577:596 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 19 theme cellular 680:687 arg1 composition 689:699 cellular composition 680:699 cellular composition 680:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 6 20 from DEGs 1255:1258 arg1 group 1278:1282 the dietary BP group 1263:1282 the dietary BP group 1263:1282 In contrast, the DEGs in the dietary BP group were related to intestinal epithelium integrity and immune response to pathogens, including S100A2, GCNT3, LYZ, SCGB1A1, SAA3, and ST3GAL1. 36011367 5 21 dep genes 1090:1094 arg1 HSP70 1104:1108 HSP70 1104:1108 HSP70 1104:1108 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 5 21 dep genes 1090:1094 arg1 HSPB6 1097:1101 HSPB6 1097:1101 HSPB6 1097:1101 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 5 21 dep genes 1090:1094 arg1 CCL4 1124:1127 CCL4 1124:1127 CCL4 1124:1127 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 5 21 dep genes 1090:1094 arg1 TAGLN 1117:1121 TAGLN 1117:1121 TAGLN 1117:1121 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 5 21 dep genes 1090:1094 arg1 TPM1 1111:1114 TPM1 1111:1114 TPM1 1111:1114 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 5 22 theme HS 1137:1138 arg1 group 1140:1144 the HS group 1133:1144 the HS group 1133:1144 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 3 23 theme filament 748:755 arg1 processes 588:596 biological processes 577:596 biological processes 577:596 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 23 theme filament 748:755 arg1 binding 757:763 actin filament binding 742:763 actin filament binding 742:763 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 24 theme actin 706:710 arg1 binding 712:718 actin binding 706:718 actin binding 706:718 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 1 25 theme expressed 271:279 arg1 genes 281:285 differentially expressed genes 256:285 differentially expressed genes 256:285 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 25 theme expressed 271:279 arg1 expression 244:253 gene expression 239:253 gene expression (differentially expressed genes, DEGs) of the porcine jejunum 239:315 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 7 26 theme fiber 1503:1507 arg1 response 1468:1475 the HS response 1461:1475 the HS response 1461:1475 These findings might help understand the HS response and the effect of dietary fiber (DF) regarding HS and be a valuable reference for future studies. 36011367 7 26 theme fiber 1503:1507 arg1 effect 1485:1490 the effect 1481:1490 the effect of dietary fiber (DF) regarding HS 1481:1525 These findings might help understand the HS response and the effect of dietary fiber (DF) regarding HS and be a valuable reference for future studies. 36011367 0 27 theme Dietary 74:80 arg1 Fiber 90:94 Dietary Soluble Fiber 74:94 Dietary Soluble Fiber from Beet Pulp 74:109 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 3 28 theme pyridoxal 770:778 arg1 processes 588:596 biological processes 577:596 biological processes 577:596 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 28 theme pyridoxal 770:778 arg1 binding 790:796 pyridoxal phosphate binding 770:796 pyridoxal phosphate binding 770:796 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 4 29 theme KEGG 829:832 arg1 analysis 842:849 The KEGG pathway analysis 825:849 The KEGG pathway analysis 825:849 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 5 30 theme oxidative 1172:1180 arg1 stress 1182:1187 cellular oxidative stress 1163:1187 cellular oxidative stress 1163:1187 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 4 31 theme hypertrophic 889:900 arg1 cardiomyopathy 902:915 hypertrophic cardiomyopathy 889:915 hypertrophic cardiomyopathy 889:915 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 0 32 theme Transcriptomic 0:13 arg1 Analysis 15:22 Transcriptomic Analysis 0:22 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 0:110 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 1 33 theme beet 221:224 arg1 BP 232:233 BP 232:233 BP 232:233 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 33 theme beet 221:224 arg1 pulp 226:229 beet pulp 221:229 beet pulp (BP) 221:234 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 34 dep genes 281:285 arg1 DEGs 288:291 DEGs 288:291 DEGs 288:291 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 0 35 theme Porcine 31:37 arg1 Gut 39:41 the Porcine Gut 27:41 the Porcine Gut 27:41 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 3 36 from regions 669:675 arg1 composition 689:699 cellular composition 680:699 cellular composition 680:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 37 theme cytoskeleton 515:526 arg1 organization 528:539 the actin cytoskeleton organization 505:539 the actin cytoskeleton organization 505:539 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 1 38 theme gene 239:242 arg1 genes 281:285 differentially expressed genes 256:285 differentially expressed genes 256:285 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 38 theme gene 239:242 arg1 expression 244:253 gene expression 239:253 gene expression (differentially expressed genes, DEGs) of the porcine jejunum 239:315 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 4 39 theme muscle 958:963 arg1 contraction 965:975 vascular smooth muscle contraction 942:975 vascular smooth muscle contraction 942:975 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 3 40 theme ontology 427:434 arg1 analysis 452:459 The gene ontology (GO) enrichment analysis 418:459 The gene ontology (GO) enrichment analysis 418:459 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 41 theme structure 552:560 arg1 development 562:572 muscle structure development 545:572 muscle structure development 545:572 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 6 42 theme intestinal 1300:1309 arg1 integrity 1322:1330 intestinal epithelium integrity 1300:1330 intestinal epithelium integrity 1300:1330 In contrast, the DEGs in the dietary BP group were related to intestinal epithelium integrity and immune response to pathogens, including S100A2, GCNT3, LYZ, SCGB1A1, SAA3, and ST3GAL1. 36011367 1 43 theme effects 183:189 arg1 impact 148:153 the impact 144:153 the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum 144:315 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 6 44 from related 1289:1295 arg1 contrast 1241:1248 contrast 1241:1248 contrast 1241:1248 In contrast, the DEGs in the dietary BP group were related to intestinal epithelium integrity and immune response to pathogens, including S100A2, GCNT3, LYZ, SCGB1A1, SAA3, and ST3GAL1. 36011367 3 45 from development 562:572 arg1 fibers 617:622 stress fibers 610:622 stress fibers 610:622 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 45 from development 562:572 arg1 binding 733:739 calcium ion binding 721:739 calcium ion binding 721:739 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 45 from development 562:572 arg1 processes 588:596 biological processes 577:596 biological processes 577:596 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 45 from development 562:572 arg1 function 815:822 the molecular function 801:822 the molecular function 801:822 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 45 from development 562:572 arg1 cytoplasm 599:607 cytoplasm 599:607 cytoplasm 599:607 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 45 from development 562:572 arg1 disc 627:630 Z disc 625:630 Z disc 625:630 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 45 from development 562:572 arg1 binding 712:718 actin binding 706:718 actin binding 706:718 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 45 from development 562:572 arg1 regions 669:675 the extracellular regions 651:675 the extracellular regions in cellular composition 651:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 45 from development 562:572 arg1 cytoskeleton 633:644 cytoskeleton 633:644 cytoskeleton 633:644 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 45 from development 562:572 arg1 binding 790:796 pyridoxal phosphate binding 770:796 pyridoxal phosphate binding 770:796 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 45 from development 562:572 arg1 binding 757:763 actin filament binding 742:763 actin filament binding 742:763 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 1 46 theme dietary 194:200 arg1 fiber 210:214 dietary soluble fiber 194:214 dietary soluble fiber from beet pulp (BP) 194:234 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 4 47 theme vascular 942:949 arg1 contraction 965:975 vascular smooth muscle contraction 942:975 vascular smooth muscle contraction 942:975 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 1 48 theme fiber 210:214 arg1 effects 183:189 the effects 179:189 the effects of dietary soluble fiber from beet pulp (BP) 179:234 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 48 theme fiber 210:214 arg1 HS 171:172 HS 171:172 HS 171:172 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 48 theme fiber 210:214 arg1 stress 163:168 heat stress 158:168 heat stress (HS) 158:173 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 7 49 theme future 1559:1564 arg1 studies 1566:1572 future studies 1559:1572 future studies 1559:1572 These findings might help understand the HS response and the effect of dietary fiber (DF) regarding HS and be a valuable reference for future studies. 36011367 4 50 theme mucin 1012:1016 arg1 biosynthesis 1032:1043 mucin type O-glycan biosynthesis 1012:1043 mucin type O-glycan biosynthesis 1012:1043 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 3 51 from organization 528:539 arg1 fibers 617:622 stress fibers 610:622 stress fibers 610:622 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 51 from organization 528:539 arg1 binding 733:739 calcium ion binding 721:739 calcium ion binding 721:739 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 51 from organization 528:539 arg1 processes 588:596 biological processes 577:596 biological processes 577:596 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 51 from organization 528:539 arg1 function 815:822 the molecular function 801:822 the molecular function 801:822 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 51 from organization 528:539 arg1 cytoplasm 599:607 cytoplasm 599:607 cytoplasm 599:607 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 51 from organization 528:539 arg1 disc 627:630 Z disc 625:630 Z disc 625:630 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 51 from organization 528:539 arg1 binding 712:718 actin binding 706:718 actin binding 706:718 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 51 from organization 528:539 arg1 regions 669:675 the extracellular regions 651:675 the extracellular regions in cellular composition 651:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 51 from organization 528:539 arg1 cytoskeleton 633:644 cytoskeleton 633:644 cytoskeleton 633:644 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 51 from organization 528:539 arg1 binding 790:796 pyridoxal phosphate binding 770:796 pyridoxal phosphate binding 770:796 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 51 from organization 528:539 arg1 binding 757:763 actin filament binding 742:763 actin filament binding 742:763 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 52 theme gene 422:425 arg1 ontology 427:434 The gene ontology 418:434 The gene ontology (GO) enrichment analysis 418:459 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 4 53 theme O-glycan 1023:1030 arg1 biosynthesis 1032:1043 mucin type O-glycan biosynthesis 1012:1043 mucin type O-glycan biosynthesis 1012:1043 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 3 54 theme stress 610:615 arg1 fibers 617:622 stress fibers 610:622 stress fibers 610:622 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 55 from fibers 617:622 arg1 composition 689:699 cellular composition 680:699 cellular composition 680:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 1 56 theme stress 163:168 arg1 impact 148:153 the impact 144:153 the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum 144:315 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 4 57 theme cytoskeleton 998:1009 arg1 cardiomyopathy 926:939 dilated cardiomyopathy 918:939 dilated cardiomyopathy 918:939 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 4 57 theme cytoskeleton 998:1009 arg1 trypanosomiasis 1058:1072 African trypanosomiasis 1050:1072 African trypanosomiasis 1050:1072 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 4 57 theme cytoskeleton 998:1009 arg1 regulation 978:987 regulation 978:987 regulation of actin cytoskeleton 978:1009 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 4 57 theme cytoskeleton 998:1009 arg1 biosynthesis 1032:1043 mucin type O-glycan biosynthesis 1012:1043 mucin type O-glycan biosynthesis 1012:1043 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 4 57 theme cytoskeleton 998:1009 arg1 cardiomyopathy 902:915 hypertrophic cardiomyopathy 889:915 hypertrophic cardiomyopathy 889:915 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 4 57 theme cytoskeleton 998:1009 arg1 contraction 965:975 vascular smooth muscle contraction 942:975 vascular smooth muscle contraction 942:975 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 1 58 theme porcine 301:307 arg1 jejunum 309:315 the porcine jejunum 297:315 the porcine jejunum 297:315 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 6 59 theme immune 1336:1341 arg1 response 1343:1350 immune response 1336:1350 immune response to pathogens, including S100A2, GCNT3, LYZ, SCGB1A1, SAA3, and ST3GAL1 1336:1421 In contrast, the DEGs in the dietary BP group were related to intestinal epithelium integrity and immune response to pathogens, including S100A2, GCNT3, LYZ, SCGB1A1, SAA3, and ST3GAL1. 36011367 3 60 theme extracellular 655:667 arg1 regions 669:675 the extracellular regions 651:675 the extracellular regions in cellular composition 651:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 1 61 from effects 183:189 arg1 BP 232:233 BP 232:233 BP 232:233 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 61 from effects 183:189 arg1 pulp 226:229 beet pulp 221:229 beet pulp (BP) 221:234 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 6 62 from contrast 1241:1248 arg1 related 1289:1295 related 1289:1295 related 1289:1295 In contrast, the DEGs in the dietary BP group were related to intestinal epithelium integrity and immune response to pathogens, including S100A2, GCNT3, LYZ, SCGB1A1, SAA3, and ST3GAL1. 36011367 6 62 from contrast 1241:1248 arg1 DEGs 1255:1258 the DEGs 1251:1258 the DEGs in the dietary BP group 1251:1282 In contrast, the DEGs in the dietary BP group were related to intestinal epithelium integrity and immune response to pathogens, including S100A2, GCNT3, LYZ, SCGB1A1, SAA3, and ST3GAL1. 36011367 0 63 theme Heat 58:61 arg1 Stress 63:68 Heat Stress 58:68 Heat Stress 58:68 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 3 64 theme calcium 721:727 arg1 binding 733:739 calcium ion binding 721:739 calcium ion binding 721:739 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 64 theme calcium 721:727 arg1 processes 588:596 biological processes 577:596 biological processes 577:596 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 4 65 theme pathway 834:840 arg1 analysis 842:849 The KEGG pathway analysis 825:849 The KEGG pathway analysis 825:849 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 4 66 theme African 1050:1056 arg1 trypanosomiasis 1058:1072 African trypanosomiasis 1050:1072 African trypanosomiasis 1050:1072 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 1 67 from impact 148:153 arg1 genes 281:285 differentially expressed genes 256:285 differentially expressed genes 256:285 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 1 67 from impact 148:153 arg1 expression 244:253 gene expression 239:253 gene expression (differentially expressed genes, DEGs) of the porcine jejunum 239:315 This study aimed to investigate the impact of heat stress (HS) and the effects of dietary soluble fiber from beet pulp (BP) on gene expression (differentially expressed genes, DEGs) of the porcine jejunum. 36011367 0 68 from Analysis 15:22 arg1 Fiber 90:94 Dietary Soluble Fiber 74:94 Dietary Soluble Fiber from Beet Pulp 74:109 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 0 68 from Analysis 15:22 arg1 Pulp 106:109 Beet Pulp 101:109 Beet Pulp 101:109 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 0 68 from Analysis 15:22 arg1 Response 46:53 Response 46:53 Response to Heat Stress 46:68 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 0 69 theme Soluble 82:88 arg1 Fiber 90:94 Dietary Soluble Fiber 74:94 Dietary Soluble Fiber from Beet Pulp 74:109 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 3 70 theme actin 742:746 arg1 processes 588:596 biological processes 577:596 biological processes 577:596 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 70 theme actin 742:746 arg1 binding 757:763 actin filament binding 742:763 actin filament binding 742:763 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 5 71 theme cellular 1163:1170 arg1 stress 1182:1187 cellular oxidative stress 1163:1187 cellular oxidative stress 1163:1187 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 3 72 theme phosphate 780:788 arg1 processes 588:596 biological processes 577:596 biological processes 577:596 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 72 theme phosphate 780:788 arg1 binding 790:796 pyridoxal phosphate binding 770:796 pyridoxal phosphate binding 770:796 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 73 from disc 627:630 arg1 composition 689:699 cellular composition 680:699 cellular composition 680:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 6 74 theme BP 1275:1276 arg1 group 1278:1282 the dietary BP group 1263:1282 the dietary BP group 1263:1282 In contrast, the DEGs in the dietary BP group were related to intestinal epithelium integrity and immune response to pathogens, including S100A2, GCNT3, LYZ, SCGB1A1, SAA3, and ST3GAL1. 36011367 3 75 from cytoskeleton 633:644 arg1 composition 689:699 cellular composition 680:699 cellular composition 680:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 76 theme molecular 805:813 arg1 function 815:822 the molecular function 801:822 the molecular function 801:822 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 0 77 theme Gut 39:41 arg1 Analysis 15:22 Transcriptomic Analysis 0:22 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 0:110 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 7 78 theme dietary 1495:1501 arg1 DF 1510:1511 DF 1510:1511 DF 1510:1511 These findings might help understand the HS response and the effect of dietary fiber (DF) regarding HS and be a valuable reference for future studies. 36011367 7 78 theme dietary 1495:1501 arg1 fiber 1503:1507 dietary fiber 1495:1507 dietary fiber (DF) 1495:1512 These findings might help understand the HS response and the effect of dietary fiber (DF) regarding HS and be a valuable reference for future studies. 36011367 7 79 theme HS 1465:1466 arg1 response 1468:1475 the HS response 1461:1475 the HS response 1461:1475 These findings might help understand the HS response and the effect of dietary fiber (DF) regarding HS and be a valuable reference for future studies. 36011367 5 80 theme genes 1090:1094 arg1 Several 1075:1081 Several 1075:1081 Several 1075:1081 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 3 81 from binding 712:718 arg1 composition 689:699 cellular composition 680:699 cellular composition 680:699 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 3 82 theme actin 509:513 arg1 organization 528:539 the actin cytoskeleton organization 505:539 the actin cytoskeleton organization 505:539 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 5 83 theme cellular 1212:1219 arg1 differentiation 1221:1235 cellular differentiation 1212:1235 cellular differentiation 1212:1235 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 4 84 theme smooth 951:956 arg1 contraction 965:975 vascular smooth muscle contraction 942:975 vascular smooth muscle contraction 942:975 The KEGG pathway analysis showed that the DEGs were involved in hypertrophic cardiomyopathy, dilated cardiomyopathy, vascular smooth muscle contraction, regulation of actin cytoskeleton, mucin type O-glycan biosynthesis, and African trypanosomiasis. 36011367 3 85 theme muscle 545:550 arg1 development 562:572 muscle structure development 545:572 muscle structure development 545:572 The gene ontology (GO) enrichment analysis showed that the DEGs were related mainly to the actin cytoskeleton organization and muscle structure development in biological processes, cytoplasm, stress fibers, Z disc, cytoskeleton, and the extracellular regions in cellular composition, and actin binding, calcium ion binding, actin filament binding, and pyridoxal phosphate binding in the molecular function. 36011367 5 86 theme immune 1190:1195 arg1 responses 1197:1205 immune responses 1190:1205 immune responses 1190:1205 Several of the genes (HSPB6, HSP70, TPM1, TAGLN, CCL4) in the HS group were involved in cellular oxidative stress, immune responses, and cellular differentiation. 36011367 6 87 theme epithelium 1311:1320 arg1 integrity 1322:1330 intestinal epithelium integrity 1300:1330 intestinal epithelium integrity 1300:1330 In contrast, the DEGs in the dietary BP group were related to intestinal epithelium integrity and immune response to pathogens, including S100A2, GCNT3, LYZ, SCGB1A1, SAA3, and ST3GAL1. 36011367 0 88 from Pulp 106:109 arg1 Fiber 90:94 Dietary Soluble Fiber 74:94 Dietary Soluble Fiber from Beet Pulp 74:109 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 0 88 from Pulp 106:109 arg1 Analysis 15:22 Transcriptomic Analysis 0:22 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 0:110 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 36011367 0 88 from Pulp 106:109 arg1 Response 46:53 Response 46:53 Response to Heat Stress 46:68 Transcriptomic Analysis of the Porcine Gut in Response to Heat Stress and Dietary Soluble Fiber from Beet Pulp. 35563010 7 0 theme signaling 1147:1155 arg1 pathways 1157:1164 intracellular signaling pathways 1133:1164 intracellular signaling pathways 1133:1164 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 9 1 with combination 1440:1450 arg1 signals 1457:1463 signals 1457:1463 signals from a dysbiotic microbiota 1457:1491 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 7 2 theme increased 1038:1046 arg1 accumulation 1048:1059 increased accumulation 1038:1059 increased accumulation of immune cells 1038:1075 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 6 3 theme greater 927:933 arg1 thickness 940:948 greater wall thickness 927:948 greater wall thickness 927:948 Results: The P2X7R+/+ mice displayed more ulcers, tumors, and greater wall thickness, than the P2X7R-/- and the P2X7R+/+ mice treated with A740003. 35563010 0 4 theme Gut 83:85 arg1 Microbiota 87:96 Gut Microbiota 83:96 Gut Microbiota 83:96 The P2X7 Receptor Promotes Colorectal Inflammation and Tumorigenesis by Modulating Gut Microbiota and the Inflammasome. 35563010 9 5 theme CA-CRC 1627:1632 arg1 development 1634:1644 CA-CRC development 1627:1644 CA-CRC development 1627:1644 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 9 6 from microbiota 1482:1491 arg1 signals 1457:1463 signals 1457:1463 signals from a dysbiotic microbiota 1457:1491 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 1 7 theme P2X7 154:157 arg1 P2X7R 169:173 P2X7R 169:173 P2X7R 169:173 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 1 7 theme P2X7 154:157 arg1 receptor 159:166 P2X7 receptor 154:166 the P2X7 receptor (P2X7R) 150:174 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 9 8 theme inflammatory 1591:1602 arg1 response 1604:1611 the inflammatory response 1587:1611 the inflammatory response 1587:1611 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 8 9 theme A740003 1349:1355 arg1 treatment 1357:1365 the A740003 treatment 1345:1365 the A740003 treatment 1345:1365 Microbial changes were observed in the P2X7R-/- and P2X7R+/+-induced mice, partially reversed by the A740003 treatment. 35563010 3 10 theme P2X7R+/+ 477:484 arg1 mice 486:489 P2X7R+/+ mice 477:489 P2X7R+/+ mice 477:489 In a therapeutic protocol, P2X7R+/+ mice were treated with a P2X7R-selective inhibitor (A740003). 35563010 7 11 theme intracellular 1133:1145 arg1 pathways 1157:1164 intracellular signaling pathways 1133:1164 intracellular signaling pathways 1133:1164 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 1 12 from role 142:145 arg1 IBD 208:210 IBD 208:210 IBD 208:210 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 1 12 from role 142:145 arg1 diseases 198:205 inflammatory bowel diseases 179:205 inflammatory bowel diseases (IBD) 179:211 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 5 13 theme microbiome 797:806 arg1 composition 808:818 microbiome composition 797:818 microbiome composition of fecal samples 797:835 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 7 14 theme NLRP3 1187:1191 arg1 upregulation 1171:1182 upregulation 1171:1182 upregulation of NLRP3 and NLRP12 genes 1171:1208 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 14 theme NLRP3 1187:1191 arg1 activation 1119:1128 activation 1119:1128 activation of intracellular signaling pathways 1119:1164 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 14 theme NLRP3 1187:1191 arg1 production 1078:1087 production 1078:1087 production of proinflammatory cytokines 1078:1116 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 14 theme NLRP3 1187:1191 arg1 accumulation 1048:1059 increased accumulation 1038:1059 increased accumulation of immune cells 1038:1075 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 4 15 theme ultrasound 616:625 arg1 biomicroscopy 627:639 endoluminal ultrasound biomicroscopy 604:639 endoluminal ultrasound biomicroscopy 604:639 Mice were evaluated with follow-up video endoscopy with endoluminal ultrasound biomicroscopy. 35563010 1 16 theme receptor 159:166 arg1 role 142:145 the role 138:145 the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD) 138:211 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 7 17 theme immune 1064:1069 arg1 cells 1071:1075 immune cells 1064:1075 immune cells 1064:1075 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 18 theme cells 1071:1075 arg1 upregulation 1171:1182 upregulation 1171:1182 upregulation of NLRP3 and NLRP12 genes 1171:1208 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 18 theme cells 1071:1075 arg1 activation 1119:1128 activation 1119:1128 activation of intracellular signaling pathways 1119:1164 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 18 theme cells 1071:1075 arg1 production 1078:1087 production 1078:1087 production of proinflammatory cytokines 1078:1116 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 18 theme cells 1071:1075 arg1 accumulation 1048:1059 increased accumulation 1038:1059 increased accumulation of immune cells 1038:1075 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 8 19 theme P2X7R-/- 1287:1294 arg1 mice 1317:1320 the P2X7R-/- and P2X7R+/+-induced mice 1283:1320 the P2X7R-/- and P2X7R+/+-induced mice 1283:1320 Microbial changes were observed in the P2X7R-/- and P2X7R+/+-induced mice, partially reversed by the A740003 treatment. 35563010 1 20 theme colitis-associated 277:294 arg1 CA-CRC 315:320 CA-CRC 315:320 CA-CRC 315:320 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 1 20 theme colitis-associated 277:294 arg1 cancer 307:312 colitis-associated colorectal cancer 277:312 colitis-associated colorectal cancer (CA-CRC) 277:321 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 0 21 theme P2X7 4:7 arg1 Receptor 9:16 The P2X7 Receptor 0:16 The P2X7 Receptor 0:16 The P2X7 Receptor Promotes Colorectal Inflammation and Tumorigenesis by Modulating Gut Microbiota and the Inflammasome. 35563010 2 22 with mice 377:380 arg1 AOM 401:403 AOM 401:403 AOM 401:403 Methods: CA-CRC was induced in P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). 35563010 2 22 with mice 377:380 arg1 azoxymethane 387:398 azoxymethane 387:398 azoxymethane (AOM) combined with dextran sodium sulfate (DSS) 387:447 Methods: CA-CRC was induced in P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). 35563010 7 23 theme pathways 1157:1164 arg1 upregulation 1171:1182 upregulation 1171:1182 upregulation of NLRP3 and NLRP12 genes 1171:1208 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 23 theme pathways 1157:1164 arg1 activation 1119:1128 activation 1119:1128 activation of intracellular signaling pathways 1119:1164 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 23 theme pathways 1157:1164 arg1 production 1078:1087 production 1078:1087 production of proinflammatory cytokines 1078:1116 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 23 theme pathways 1157:1164 arg1 accumulation 1048:1059 increased accumulation 1038:1059 increased accumulation of immune cells 1038:1075 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 9 24 theme intracellular 1521:1533 arg1 pathways 1545:1552 intracellular signaling pathways 1521:1552 intracellular signaling pathways 1521:1552 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 7 25 theme proinflammatory 1092:1106 arg1 cytokines 1108:1116 proinflammatory cytokines 1092:1116 proinflammatory cytokines 1092:1116 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 4 26 theme video 583:587 arg1 endoscopy 589:597 follow-up video endoscopy 573:597 follow-up video endoscopy with endoluminal ultrasound biomicroscopy 573:639 Mice were evaluated with follow-up video endoscopy with endoluminal ultrasound biomicroscopy. 35563010 7 27 theme cytokines 1108:1116 arg1 upregulation 1171:1182 upregulation 1171:1182 upregulation of NLRP3 and NLRP12 genes 1171:1208 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 27 theme cytokines 1108:1116 arg1 activation 1119:1128 activation 1119:1128 activation of intracellular signaling pathways 1119:1164 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 27 theme cytokines 1108:1116 arg1 production 1078:1087 production 1078:1087 production of proinflammatory cytokines 1078:1116 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 27 theme cytokines 1108:1116 arg1 accumulation 1048:1059 increased accumulation 1038:1059 increased accumulation of immune cells 1038:1075 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 8 28 theme P2X7R+/+-induced 1300:1315 arg1 mice 1317:1320 the P2X7R-/- and P2X7R+/+-induced mice 1283:1320 the P2X7R-/- and P2X7R+/+-induced mice 1283:1320 Microbial changes were observed in the P2X7R-/- and P2X7R+/+-induced mice, partially reversed by the A740003 treatment. 35563010 4 29 theme endoluminal 604:614 arg1 biomicroscopy 627:639 endoluminal ultrasound biomicroscopy 604:639 endoluminal ultrasound biomicroscopy 604:639 Mice were evaluated with follow-up video endoscopy with endoluminal ultrasound biomicroscopy. 35563010 9 30 theme Regulatory 1381:1390 arg1 mechanisms 1392:1401 Regulatory mechanisms 1381:1401 Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota 1381:1491 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 6 31 theme P2X7R-/- 960:967 arg1 mice 986:989 the P2X7R-/- and the P2X7R+/+ mice 956:989 the P2X7R-/- and the P2X7R+/+ mice treated with A740003 956:1010 Results: The P2X7R+/+ mice displayed more ulcers, tumors, and greater wall thickness, than the P2X7R-/- and the P2X7R+/+ mice treated with A740003. 35563010 5 32 theme DNA 776:778 arg1 factors 749:755 transcription factors 735:755 transcription factors 735:755 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 32 theme DNA 776:778 arg1 methylation 780:790 DNA methylation 776:790 DNA methylation 776:790 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 9 33 theme signaling 1535:1543 arg1 pathways 1545:1552 intracellular signaling pathways 1521:1552 intracellular signaling pathways 1521:1552 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 1 34 from role 234:237 arg1 development 246:256 development 246:256 development 246:256 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 1 34 from role 234:237 arg1 progression 262:272 progression 262:272 progression 262:272 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 1 35 theme inflammatory 179:190 arg1 IBD 208:210 IBD 208:210 IBD 208:210 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 1 35 theme inflammatory 179:190 arg1 diseases 198:205 inflammatory bowel diseases 179:205 inflammatory bowel diseases (IBD) 179:211 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 2 36 theme sodium 428:433 arg1 DSS 444:446 DSS 444:446 DSS 444:446 Methods: CA-CRC was induced in P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). 35563010 2 36 theme sodium 428:433 arg1 sulfate 435:441 dextran sodium sulfate 420:441 dextran sodium sulfate (DSS) 420:447 Methods: CA-CRC was induced in P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). 35563010 1 37 theme bowel 192:196 arg1 IBD 208:210 IBD 208:210 IBD 208:210 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 1 37 theme bowel 192:196 arg1 diseases 198:205 inflammatory bowel diseases 179:205 inflammatory bowel diseases (IBD) 179:211 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 5 38 theme fecal 823:827 arg1 samples 829:835 fecal samples 823:835 fecal samples 823:835 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 2 39 theme P2X7R-/- 368:375 arg1 mice 377:380 P2X7R+/+ and P2X7R-/- mice 355:380 P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS) 355:447 Methods: CA-CRC was induced in P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). 35563010 0 40 theme Colorectal 27:36 arg1 Inflammation 38:49 Inflammation 38:49 Inflammation 38:49 The P2X7 Receptor Promotes Colorectal Inflammation and Tumorigenesis by Modulating Gut Microbiota and the Inflammasome. 35563010 2 41 theme dextran 420:426 arg1 DSS 444:446 DSS 444:446 DSS 444:446 Methods: CA-CRC was induced in P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). 35563010 2 41 theme dextran 420:426 arg1 sulfate 435:441 dextran sodium sulfate 420:441 dextran sodium sulfate (DSS) 420:447 Methods: CA-CRC was induced in P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). 35563010 9 42 from P2X7R 1431:1435 arg1 combination 1440:1450 combination 1440:1450 combination with signals from a dysbiotic microbiota 1440:1491 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 4 43 theme follow-up 573:581 arg1 endoscopy 589:597 follow-up video endoscopy 573:597 follow-up video endoscopy with endoluminal ultrasound biomicroscopy 573:639 Mice were evaluated with follow-up video endoscopy with endoluminal ultrasound biomicroscopy. 35563010 5 44 theme factors 749:755 arg1 densities 694:702 densities 694:702 densities of immune cells 694:718 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 44 theme factors 749:755 arg1 composition 808:818 microbiome composition 797:818 microbiome composition of fecal samples 797:835 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 44 theme factors 749:755 arg1 changes 685:691 histological changes 672:691 histological changes 672:691 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 44 theme factors 749:755 arg1 expression 721:730 expression 721:730 expression of transcription factors, cytokines, genes, DNA methylation 721:790 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 6 45 theme P2X7R+/+ 878:885 arg1 mice 887:890 The P2X7R+/+ mice 874:890 The P2X7R+/+ mice 874:890 Results: The P2X7R+/+ mice displayed more ulcers, tumors, and greater wall thickness, than the P2X7R-/- and the P2X7R+/+ mice treated with A740003. 35563010 4 46 with endoscopy 589:597 arg1 biomicroscopy 627:639 endoluminal ultrasound biomicroscopy 604:639 endoluminal ultrasound biomicroscopy 604:639 Mice were evaluated with follow-up video endoscopy with endoluminal ultrasound biomicroscopy. 35563010 3 47 theme P2X7R-selective 511:525 arg1 A740003 538:544 A740003 538:544 A740003 538:544 In a therapeutic protocol, P2X7R+/+ mice were treated with a P2X7R-selective inhibitor (A740003). 35563010 3 47 theme P2X7R-selective 511:525 arg1 inhibitor 527:535 a P2X7R-selective inhibitor 509:535 a P2X7R-selective inhibitor (A740003) 509:545 In a therapeutic protocol, P2X7R+/+ mice were treated with a P2X7R-selective inhibitor (A740003). 35563010 8 48 theme Microbial 1248:1256 arg1 changes 1258:1264 Microbial changes 1248:1264 Microbial changes 1248:1264 Microbial changes were observed in the P2X7R-/- and P2X7R+/+-induced mice, partially reversed by the A740003 treatment. 35563010 5 49 theme histological 672:683 arg1 changes 685:691 histological changes 672:691 histological changes 672:691 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 2 50 theme P2X7R+/+ 355:362 arg1 mice 377:380 P2X7R+/+ and P2X7R-/- mice 355:380 P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS) 355:447 Methods: CA-CRC was induced in P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). 35563010 1 51 dep development 246:256 arg1 the 242:244 the 242:244 the 242:244 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 6 52 dep more 902:905 arg1 ulcers 907:912 ulcers 907:912 ulcers 907:912 Results: The P2X7R+/+ mice displayed more ulcers, tumors, and greater wall thickness, than the P2X7R-/- and the P2X7R+/+ mice treated with A740003. 35563010 7 53 theme P2X7R+/+ 1017:1024 arg1 mice 1026:1029 The P2X7R+/+ mice 1013:1029 The P2X7R+/+ mice 1013:1029 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 1 54 theme colorectal 296:305 arg1 CA-CRC 315:320 CA-CRC 315:320 CA-CRC 315:320 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 1 54 theme colorectal 296:305 arg1 cancer 307:312 colitis-associated colorectal cancer 277:312 colitis-associated colorectal cancer (CA-CRC) 277:321 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 5 55 theme Colon 642:646 arg1 tissue 648:653 Colon tissue 642:653 Colon tissue 642:653 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 9 56 theme dysbiotic 1472:1480 arg1 microbiota 1482:1491 a dysbiotic microbiota 1470:1491 a dysbiotic microbiota 1470:1491 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 7 57 theme NLRP12 1197:1202 arg1 genes 1204:1208 NLRP12 genes 1197:1208 NLRP12 genes 1197:1208 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 9 58 theme pathways 1545:1552 arg1 activation 1507:1516 the activation 1503:1516 the activation of intracellular signaling pathways 1503:1552 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 9 58 theme pathways 1545:1552 arg1 inflammasome 1562:1573 the inflammasome 1558:1573 the inflammasome 1558:1573 Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development. 35563010 8 59 located observed 1271:1278 arg1 mice 1317:1320 the P2X7R-/- and P2X7R+/+-induced mice 1283:1320 the P2X7R-/- and P2X7R+/+-induced mice 1283:1320 Microbial changes were observed in the P2X7R-/- and P2X7R+/+-induced mice, partially reversed by the A740003 treatment. 35563010 8 59 located observed 1271:1278 arg2 changes 1258:1264 Microbial changes 1248:1264 Microbial changes 1248:1264 Microbial changes were observed in the P2X7R-/- and P2X7R+/+-induced mice, partially reversed by the A740003 treatment. 35563010 6 60 theme P2X7R+/+ 977:984 arg1 mice 986:989 the P2X7R-/- and the P2X7R+/+ mice 956:989 the P2X7R-/- and the P2X7R+/+ mice treated with A740003 956:1010 Results: The P2X7R+/+ mice displayed more ulcers, tumors, and greater wall thickness, than the P2X7R-/- and the P2X7R+/+ mice treated with A740003. 35563010 7 61 theme genes 1204:1208 arg1 upregulation 1171:1182 upregulation 1171:1182 upregulation of NLRP3 and NLRP12 genes 1171:1208 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 61 theme genes 1204:1208 arg1 activation 1119:1128 activation 1119:1128 activation of intracellular signaling pathways 1119:1164 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 61 theme genes 1204:1208 arg1 production 1078:1087 production 1078:1087 production of proinflammatory cytokines 1078:1116 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 7 61 theme genes 1204:1208 arg1 accumulation 1048:1059 increased accumulation 1038:1059 increased accumulation of immune cells 1038:1075 The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. 35563010 5 62 theme immune 707:712 arg1 cells 714:718 immune cells 707:718 immune cells 707:718 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 63 theme samples 829:835 arg1 densities 694:702 densities 694:702 densities of immune cells 694:718 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 63 theme samples 829:835 arg1 composition 808:818 microbiome composition 797:818 microbiome composition of fecal samples 797:835 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 63 theme samples 829:835 arg1 changes 685:691 histological changes 672:691 histological changes 672:691 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 63 theme samples 829:835 arg1 expression 721:730 expression 721:730 expression of transcription factors, cytokines, genes, DNA methylation 721:790 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 64 theme cells 714:718 arg1 densities 694:702 densities 694:702 densities of immune cells 694:718 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 64 theme cells 714:718 arg1 composition 808:818 microbiome composition 797:818 microbiome composition of fecal samples 797:835 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 64 theme cells 714:718 arg1 changes 685:691 histological changes 672:691 histological changes 672:691 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 64 theme cells 714:718 arg1 expression 721:730 expression 721:730 expression of transcription factors, cytokines, genes, DNA methylation 721:790 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 1 65 theme cancer 307:312 arg1 development 246:256 development 246:256 development 246:256 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 1 65 theme cancer 307:312 arg1 progression 262:272 progression 262:272 progression 262:272 Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). 35563010 5 66 theme transcription 735:747 arg1 factors 749:755 transcription factors 735:755 transcription factors 735:755 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 66 theme transcription 735:747 arg1 genes 769:773 genes 769:773 genes 769:773 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 66 theme transcription 735:747 arg1 methylation 780:790 DNA methylation 776:790 DNA methylation 776:790 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 5 66 theme transcription 735:747 arg1 cytokines 758:766 cytokines 758:766 cytokines 758:766 Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. 35563010 3 67 theme therapeutic 455:465 arg1 protocol 467:474 a therapeutic protocol 453:474 a therapeutic protocol 453:474 In a therapeutic protocol, P2X7R+/+ mice were treated with a P2X7R-selective inhibitor (A740003). 35563010 6 68 theme wall 935:938 arg1 thickness 940:948 greater wall thickness 927:948 greater wall thickness 927:948 Results: The P2X7R+/+ mice displayed more ulcers, tumors, and greater wall thickness, than the P2X7R-/- and the P2X7R+/+ mice treated with A740003. 35719161 5 0 theme electron 757:764 arg1 SEM 778:780 SEM 778:780 SEM 778:780 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 5 0 theme electron 757:764 arg1 microscope 766:775 scanning electron microscope 748:775 scanning electron microscope (SEM) 748:781 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 3 1 theme polydispersity 490:503 arg1 0.260 521:525 0.260 521:525 0.260 521:525 Then, the particle size of ZOP-NPs prepared by nano-precipitation method was 230.5 nm, and the polydispersity index (PDI) was 0.260. 35719161 3 1 theme polydispersity 490:503 arg1 index 505:509 the polydispersity index 486:509 the polydispersity index (PDI) 486:515 Then, the particle size of ZOP-NPs prepared by nano-precipitation method was 230.5 nm, and the polydispersity index (PDI) was 0.260. 35719161 3 1 theme polydispersity 490:503 arg1 PDI 512:514 PDI 512:514 PDI 512:514 Then, the particle size of ZOP-NPs prepared by nano-precipitation method was 230.5 nm, and the polydispersity index (PDI) was 0.260. 35719161 1 2 theme assisted 263:270 arg1 method 283:288 ultrasonic assisted extraction method 252:288 ultrasonic assisted extraction method 252:288 A novel polysaccharide (ZOP) was extracted from Zingiber officinale with ultrasonic assisted extraction method. 35719161 0 3 theme Polysaccharide 81:94 arg1 Application 129:139 Its Application 125:139 Its Application in Synthesis of Silver Nanoparticles 125:176 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 3 theme Polysaccharide 81:94 arg1 Antioxidant 29:39 Antioxidant 29:39 Antioxidant 29:39 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 3 theme Polysaccharide 81:94 arg1 Activities 59:68 Antibacterial Activities 45:68 Antibacterial Activities 45:68 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 3 theme Polysaccharide 81:94 arg1 Characterization 11:26 Structural Characterization 0:26 Structural Characterization 0:26 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 4 from Characterization 11:26 arg1 Synthesis 144:152 Synthesis 144:152 Synthesis of Silver Nanoparticles 144:176 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 4 from Characterization 11:26 arg1 officinale 110:119 Zingiber officinale 101:119 Zingiber officinale 101:119 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 6 5 dep 82.12 947:951 arg1 to 944:945 to 944:945 to 944:945 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) ranged from 68.70 to 82.12%. 35719161 1 6 theme extraction 272:281 arg1 method 283:288 ultrasonic assisted extraction method 252:288 ultrasonic assisted extraction method 252:288 A novel polysaccharide (ZOP) was extracted from Zingiber officinale with ultrasonic assisted extraction method. 35719161 6 7 theme chelation 864:872 arg1 rate 874:877 The silver chelation rate 853:877 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) 853:924 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) ranged from 68.70 to 82.12%. 35719161 2 8 dep Gal 357:359 arg1 Ara 362:364 Ara 362:364 Ara 362:364 ZOP monosaccharide composition and mole ratio is GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07. 35719161 9 9 theme ZOP-NPs-AgNPs 1249:1261 arg1 superior 1268:1275 superior 1268:1275 superior 1268:1275 The antioxidant and antibacterial activities of ZOP-NPs-AgNPs were superior to those of ZOP, ZOP-NPs and ZOP-AgNPs. 35719161 9 9 theme ZOP-NPs-AgNPs 1249:1261 arg1 activities 1235:1244 The antioxidant and antibacterial activities 1201:1244 The antioxidant and antibacterial activities of ZOP-NPs-AgNPs 1201:1261 The antioxidant and antibacterial activities of ZOP-NPs-AgNPs were superior to those of ZOP, ZOP-NPs and ZOP-AgNPs. 35719161 0 10 theme Zingiber 101:108 arg1 officinale 110:119 Zingiber officinale 101:119 Zingiber officinale 101:119 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 6 11 theme silver 857:862 arg1 rate 874:877 The silver chelation rate 853:877 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) 853:924 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) ranged from 68.70 to 82.12%. 35719161 5 12 theme ultraviolet-visible 651:669 arg1 fourier 699:705 fourier 699:705 fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD) 699:850 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 5 12 theme ultraviolet-visible 651:669 arg1 spectrophotometer 671:687 ultraviolet-visible spectrophotometer 651:687 ultraviolet-visible spectrophotometer (UV-Vis) 651:696 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 5 13 dep spectrophotometer 671:687 arg1 UV-Vis 690:695 UV-Vis 690:695 UV-Vis 690:695 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 0 14 from Activities 59:68 arg1 Synthesis 144:152 Synthesis 144:152 Synthesis of Silver Nanoparticles 144:176 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 14 from Activities 59:68 arg1 officinale 110:119 Zingiber officinale 101:119 Zingiber officinale 101:119 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 2 15 theme monosaccharide 295:308 arg1 composition 310:320 ZOP monosaccharide composition 291:320 ZOP monosaccharide composition 291:320 ZOP monosaccharide composition and mole ratio is GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07. 35719161 1 16 theme novel 181:185 arg1 ZOP 203:205 ZOP 203:205 ZOP 203:205 A novel polysaccharide (ZOP) was extracted from Zingiber officinale with ultrasonic assisted extraction method. 35719161 1 16 theme novel 181:185 arg1 polysaccharide 187:200 A novel polysaccharide 179:200 A novel polysaccharide (ZOP) 179:206 A novel polysaccharide (ZOP) was extracted from Zingiber officinale with ultrasonic assisted extraction method. 35719161 7 17 theme size 1053:1056 arg1 distribution 1058:1069 a narrow particle size distribution 1035:1069 a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively 1035:1115 ZOP-AgNPs (0.5%, w/v; 1%, w/v) and ZOP-NPs-AgNPs (0.5%, w/v; 1%, w/v) exhibited a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively. 35719161 3 18 theme particle 405:412 arg1 nm 478:479 230.5 nm 472:479 230.5 nm 472:479 Then, the particle size of ZOP-NPs prepared by nano-precipitation method was 230.5 nm, and the polydispersity index (PDI) was 0.260. 35719161 3 18 theme particle 405:412 arg1 size 414:417 the particle size 401:417 the particle size of ZOP-NPs prepared by nano-precipitation method 401:466 Then, the particle size of ZOP-NPs prepared by nano-precipitation method was 230.5 nm, and the polydispersity index (PDI) was 0.260. 35719161 2 19 theme ZOP 291:293 arg1 composition 310:320 ZOP monosaccharide composition 291:320 ZOP monosaccharide composition 291:320 ZOP monosaccharide composition and mole ratio is GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07. 35719161 6 20 theme polysaccharide 882:895 arg1 AgNPs 919:923 AgNPs 919:923 AgNPs 919:923 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) ranged from 68.70 to 82.12%. 35719161 6 20 theme polysaccharide 882:895 arg1 nanoparticles 904:916 polysaccharide silver nanoparticles 882:916 polysaccharide silver nanoparticles (AgNPs) 882:924 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) ranged from 68.70 to 82.12%. 35719161 5 21 theme transmission 784:795 arg1 TEM 818:820 TEM 818:820 TEM 818:820 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 5 21 theme transmission 784:795 arg1 microscope 806:815 transmission electron microscope 784:815 transmission electron microscope (TEM) 784:821 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 5 22 dep fourier 699:705 arg1 transform 707:715 transform 707:715 transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD) 707:850 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 5 23 dep transform 707:715 arg1 infrared 717:724 infrared 717:724 transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD) 707:850 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 7 24 dep % 969:969 arg1 w/v 981:983 w/v 981:983 w/v 981:983 ZOP-AgNPs (0.5%, w/v; 1%, w/v) and ZOP-NPs-AgNPs (0.5%, w/v; 1%, w/v) exhibited a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively. 35719161 7 24 dep % 969:969 arg1 % 978:978 1% 977:978 1% 977:978 ZOP-AgNPs (0.5%, w/v; 1%, w/v) and ZOP-NPs-AgNPs (0.5%, w/v; 1%, w/v) exhibited a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively. 35719161 0 25 theme Structural 0:9 arg1 Characterization 11:26 Structural Characterization 0:26 Structural Characterization 0:26 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 3 26 theme ZOP-NPs 422:428 arg1 nm 478:479 230.5 nm 472:479 230.5 nm 472:479 Then, the particle size of ZOP-NPs prepared by nano-precipitation method was 230.5 nm, and the polydispersity index (PDI) was 0.260. 35719161 3 26 theme ZOP-NPs 422:428 arg1 size 414:417 the particle size 401:417 the particle size of ZOP-NPs prepared by nano-precipitation method 401:466 Then, the particle size of ZOP-NPs prepared by nano-precipitation method was 230.5 nm, and the polydispersity index (PDI) was 0.260. 35719161 5 27 theme electron 797:804 arg1 TEM 818:820 TEM 818:820 TEM 818:820 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 5 27 theme electron 797:804 arg1 microscope 806:815 transmission electron microscope 784:815 transmission electron microscope (TEM) 784:821 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 2 28 theme mole 326:329 arg1 ratio 331:335 mole ratio 326:335 mole ratio 326:335 ZOP monosaccharide composition and mole ratio is GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07. 35719161 0 29 theme Antibacterial 45:57 arg1 Activities 59:68 Antibacterial Activities 45:68 Antibacterial Activities 45:68 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 7 30 theme particle 1044:1051 arg1 distribution 1058:1069 a narrow particle size distribution 1035:1069 a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively 1035:1115 ZOP-AgNPs (0.5%, w/v; 1%, w/v) and ZOP-NPs-AgNPs (0.5%, w/v; 1%, w/v) exhibited a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively. 35719161 7 31 theme narrow 1037:1042 arg1 distribution 1058:1069 a narrow particle size distribution 1035:1069 a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively 1035:1115 ZOP-AgNPs (0.5%, w/v; 1%, w/v) and ZOP-NPs-AgNPs (0.5%, w/v; 1%, w/v) exhibited a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively. 35719161 3 32 theme nano-precipitation 442:459 arg1 method 461:466 nano-precipitation method 442:466 nano-precipitation method 442:466 Then, the particle size of ZOP-NPs prepared by nano-precipitation method was 230.5 nm, and the polydispersity index (PDI) was 0.260. 35719161 5 33 theme X-ray 828:832 arg1 diffraction 834:844 X-ray diffraction 828:844 X-ray diffraction (XRD) 828:850 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 5 33 theme X-ray 828:832 arg1 XRD 847:849 XRD 847:849 XRD 847:849 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 0 34 theme Nanoparticles 164:176 arg1 Synthesis 144:152 Synthesis 144:152 Synthesis of Silver Nanoparticles 144:176 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 6 35 theme nanoparticles 904:916 arg1 rate 874:877 The silver chelation rate 853:877 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) 853:924 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) ranged from 68.70 to 82.12%. 35719161 0 36 theme Silver 157:162 arg1 Nanoparticles 164:176 Silver Nanoparticles 157:176 Silver Nanoparticles 157:176 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 6 37 theme silver 897:902 arg1 AgNPs 919:923 AgNPs 919:923 AgNPs 919:923 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) ranged from 68.70 to 82.12%. 35719161 6 37 theme silver 897:902 arg1 nanoparticles 904:916 polysaccharide silver nanoparticles 882:916 polysaccharide silver nanoparticles (AgNPs) 882:924 The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) ranged from 68.70 to 82.12%. 35719161 8 38 dep values 1141:1146 arg1 were-19.4 1156:1164 were-19.4 1156:1164 were-19.4 1156:1164 And the zeta potential values of them were-19.4,-21.6,-19.7,-23.8mV, respectively. 35719161 8 38 dep values 1141:1146 arg1 -23.8mV 1178:1184 -23.8mV 1178:1184 -23.8mV 1178:1184 And the zeta potential values of them were-19.4,-21.6,-19.7,-23.8mV, respectively. 35719161 2 39 dep GlcA 340:343 arg1 Gal 357:359 Gal 357:359 Gal 357:359 ZOP monosaccharide composition and mole ratio is GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07. 35719161 2 39 dep GlcA 340:343 arg1 Glc 352:354 Glc 352:354 GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07 340:392 ZOP monosaccharide composition and mole ratio is GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07. 35719161 2 39 dep GlcA 340:343 arg1 GalA 346:349 GalA 346:349 GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07 340:392 ZOP monosaccharide composition and mole ratio is GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07. 35719161 1 40 theme Zingiber 227:234 arg1 officinale 236:245 Zingiber officinale 227:245 Zingiber officinale 227:245 A novel polysaccharide (ZOP) was extracted from Zingiber officinale with ultrasonic assisted extraction method. 35719161 7 41 dep % 1008:1008 arg1 w/v 1020:1022 w/v 1020:1022 w/v 1020:1022 ZOP-AgNPs (0.5%, w/v; 1%, w/v) and ZOP-NPs-AgNPs (0.5%, w/v; 1%, w/v) exhibited a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively. 35719161 7 41 dep % 1008:1008 arg1 % 1017:1017 1% 1016:1017 1% 1016:1017 ZOP-AgNPs (0.5%, w/v; 1%, w/v) and ZOP-NPs-AgNPs (0.5%, w/v; 1%, w/v) exhibited a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively. 35719161 0 42 from officinale 110:119 arg1 Polysaccharide 81:94 a Novel Polysaccharide 73:94 a Novel Polysaccharide From Zingiber officinale 73:119 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 42 from officinale 110:119 arg1 Application 129:139 Its Application 125:139 Its Application in Synthesis of Silver Nanoparticles 125:176 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 42 from officinale 110:119 arg1 Antioxidant 29:39 Antioxidant 29:39 Antioxidant 29:39 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 42 from officinale 110:119 arg1 Activities 59:68 Antibacterial Activities 45:68 Antibacterial Activities 45:68 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 42 from officinale 110:119 arg1 Characterization 11:26 Structural Characterization 0:26 Structural Characterization 0:26 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 2 43 dep = 366:366 arg1 1.97:1.15:94.33:1.48:1.07 368:392 1.97:1.15:94.33:1.48:1.07 368:392 1.97:1.15:94.33:1.48:1.07 368:392 ZOP monosaccharide composition and mole ratio is GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07. 35719161 8 44 theme potential 1131:1139 arg1 values 1141:1146 And the zeta potential values 1118:1146 values 1141:1146 And the zeta potential values of them were-19.4,-21.6,-19.7,-23.8mV, respectively. 35719161 9 45 theme antioxidant 1205:1215 arg1 superior 1268:1275 superior 1268:1275 superior 1268:1275 The antioxidant and antibacterial activities of ZOP-NPs-AgNPs were superior to those of ZOP, ZOP-NPs and ZOP-AgNPs. 35719161 9 45 theme antioxidant 1205:1215 arg1 activities 1235:1244 The antioxidant and antibacterial activities 1201:1244 The antioxidant and antibacterial activities of ZOP-NPs-AgNPs 1201:1261 The antioxidant and antibacterial activities of ZOP-NPs-AgNPs were superior to those of ZOP, ZOP-NPs and ZOP-AgNPs. 35719161 0 46 theme Novel 75:79 arg1 Polysaccharide 81:94 a Novel Polysaccharide 73:94 a Novel Polysaccharide From Zingiber officinale 73:119 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 8 47 theme them 1151:1154 arg1 values 1141:1146 And the zeta potential values 1118:1146 values 1141:1146 And the zeta potential values of them were-19.4,-21.6,-19.7,-23.8mV, respectively. 35719161 5 48 theme scanning 748:755 arg1 SEM 778:780 SEM 778:780 SEM 778:780 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 5 48 theme scanning 748:755 arg1 microscope 766:775 scanning electron microscope 748:775 scanning electron microscope (SEM) 748:781 They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). 35719161 0 49 from Antioxidant 29:39 arg1 Synthesis 144:152 Synthesis 144:152 Synthesis of Silver Nanoparticles 144:176 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 49 from Antioxidant 29:39 arg1 officinale 110:119 Zingiber officinale 101:119 Zingiber officinale 101:119 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 50 from Application 129:139 arg1 Synthesis 144:152 Synthesis 144:152 Synthesis of Silver Nanoparticles 144:176 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 0 50 from Application 129:139 arg1 officinale 110:119 Zingiber officinale 101:119 Zingiber officinale 101:119 Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles. 35719161 7 51 theme nm 1100:1101 arg1 distribution 1058:1069 a narrow particle size distribution 1035:1069 a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively 1035:1115 ZOP-AgNPs (0.5%, w/v; 1%, w/v) and ZOP-NPs-AgNPs (0.5%, w/v; 1%, w/v) exhibited a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively. 35719161 9 52 theme antibacterial 1221:1233 arg1 superior 1268:1275 superior 1268:1275 superior 1268:1275 The antioxidant and antibacterial activities of ZOP-NPs-AgNPs were superior to those of ZOP, ZOP-NPs and ZOP-AgNPs. 35719161 9 52 theme antibacterial 1221:1233 arg1 activities 1235:1244 The antioxidant and antibacterial activities 1201:1244 The antioxidant and antibacterial activities of ZOP-NPs-AgNPs 1201:1261 The antioxidant and antibacterial activities of ZOP-NPs-AgNPs were superior to those of ZOP, ZOP-NPs and ZOP-AgNPs. 35719161 1 53 theme ultrasonic 252:261 arg1 method 283:288 ultrasonic assisted extraction method 252:288 ultrasonic assisted extraction method 252:288 A novel polysaccharide (ZOP) was extracted from Zingiber officinale with ultrasonic assisted extraction method. 35268609 0 0 from Characterization 14:29 arg1 Decoction 74:82 Decoction 74:82 Decoction 74:82 Isolation and Characterization of Natural Nanoparticles in Naoluo Xintong Decoction and Their Brain Protection Research. 35268609 6 1 theme apoptosis 1322:1330 arg1 level 1332:1336 apoptosis level 1322:1336 apoptosis level 1322:1336 After administration, the neurological function, histopathological changes, oxidative stress, and apoptosis level were measured. 35268609 1 2 theme traditional 258:268 arg1 TCM 288:290 TCM 288:290 TCM 288:290 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 1 2 theme traditional 258:268 arg1 medicine 278:285 traditional Chinese medicine 258:285 traditional Chinese medicine (TCM) 258:291 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 3 3 theme size 697:700 arg1 distribution 702:713 their size distribution 691:713 their size distribution 691:713 Firstly, the dialysis-centrifugation method was used to separate the nanoparticles and then their size distribution, potential, and morphology were characterized. 35268609 1 4 theme Chinese 270:276 arg1 TCM 288:290 TCM 288:290 TCM 288:290 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 1 4 theme Chinese 270:276 arg1 medicine 278:285 traditional Chinese medicine 258:285 traditional Chinese medicine (TCM) 258:291 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 0 5 theme Protection 100:109 arg1 Research 111:118 Their Brain Protection Research 88:118 Their Brain Protection Research 88:118 Isolation and Characterization of Natural Nanoparticles in Naoluo Xintong Decoction and Their Brain Protection Research. 35268609 0 6 from Isolation 0:8 arg1 Decoction 74:82 Decoction 74:82 Decoction 74:82 Isolation and Characterization of Natural Nanoparticles in Naoluo Xintong Decoction and Their Brain Protection Research. 35268609 9 7 theme NLXT 1707:1710 arg1 effect 1697:1702 the brain-protective effect 1676:1702 the brain-protective effect 1676:1702 However, removing nanoparticles can significantly reduce the brain-protective effect of NLXT, which indicates that NLXT-NPs play an essential role in the efficacy of NLXT. 35268609 4 8 theme infrared 775:782 arg1 spectroscopy 784:795 infrared spectroscopy 775:795 infrared spectroscopy 775:795 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 1 9 theme medicine 278:285 arg1 composition 243:253 the phase composition 233:253 the phase composition of traditional Chinese medicine (TCM) 233:291 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 0 10 theme Brain 94:98 arg1 Research 111:118 Their Brain Protection Research 88:118 Their Brain Protection Research 88:118 Isolation and Characterization of Natural Nanoparticles in Naoluo Xintong Decoction and Their Brain Protection Research. 35268609 7 11 theme hundred-nanometer 1487:1503 arg1 size 1505:1508 two hundred-nanometer size 1483:1508 two hundred-nanometer size 1483:1508 Our research showed that NLXT-NPs are mainly composed of polysaccharides, proteins, and saponins, with typical characteristics of two hundred-nanometer size and negatively loaded. 35268609 6 12 theme oxidative 1300:1308 arg1 stress 1310:1315 oxidative stress 1300:1315 oxidative stress 1300:1315 After administration, the neurological function, histopathological changes, oxidative stress, and apoptosis level were measured. 35268609 2 13 theme protection 520:529 arg1 related 557:563 related 557:563 related 557:563 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 2 13 theme protection 520:529 arg1 effect 531:536 the brain protection effect 510:536 the brain protection effect of NLXT 510:544 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 7 14 theme size 1505:1508 arg1 characteristics 1464:1478 typical characteristics 1456:1478 typical characteristics of two hundred-nanometer size 1456:1508 Our research showed that NLXT-NPs are mainly composed of polysaccharides, proteins, and saponins, with typical characteristics of two hundred-nanometer size and negatively loaded. 35268609 2 15 theme brain 514:518 arg1 related 557:563 related 557:563 related 557:563 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 2 15 theme brain 514:518 arg1 effect 531:536 the brain protection effect 510:536 the brain protection effect of NLXT 510:544 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 8 16 theme oxidative 1573:1581 arg1 stress 1583:1588 oxidative stress 1573:1588 oxidative stress 1573:1588 NLXT can improve nerve function, reduce oxidative stress, and inhibit cell apoptosis. 35268609 4 17 theme UPLC-Q-TOF-MS 891:903 arg1 technology 906:915 flight-mass spectrometer (UPLC-Q-TOF-MS) technology 865:915 flight-mass spectrometer (UPLC-Q-TOF-MS) technology 865:915 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 5 18 with sham 1063:1066 arg1 NLXT-RN+NPs 1189:1199 NLXT-RN+NPs 1189:1199 NLXT-RN+NPs 1189:1199 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 5 18 with sham 1063:1066 arg1 groups 1216:1221 NLXT-NPs groups 1207:1221 NLXT-NPs groups 1207:1221 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 5 18 with sham 1063:1066 arg1 nanoparticles 1132:1144 nanoparticles 1132:1144 nanoparticles removing (NLXT-RN) 1132:1163 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 5 18 with sham 1063:1066 arg1 NLXT-RN 1156:1162 NLXT-RN 1156:1162 NLXT-RN 1156:1162 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 5 18 with sham 1063:1066 arg1 NLXT-RN+Nanoparticles 1166:1186 NLXT-RN+Nanoparticles 1166:1186 NLXT-RN+Nanoparticles (NLXT-RN+NPs) 1166:1200 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 1 19 theme unique 182:187 arg1 perspective 189:199 a unique perspective 180:199 a unique perspective of physical pharmacy 180:220 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 6 20 theme histopathological 1273:1289 arg1 changes 1291:1297 histopathological changes 1273:1297 histopathological changes 1273:1297 After administration, the neurological function, histopathological changes, oxidative stress, and apoptosis level were measured. 35268609 8 21 theme nerve 1550:1554 arg1 function 1556:1563 nerve function 1550:1563 nerve function 1550:1563 NLXT can improve nerve function, reduce oxidative stress, and inhibit cell apoptosis. 35268609 7 22 theme typical 1456:1462 arg1 characteristics 1464:1478 typical characteristics 1456:1478 typical characteristics of two hundred-nanometer size 1456:1508 Our research showed that NLXT-NPs are mainly composed of polysaccharides, proteins, and saponins, with typical characteristics of two hundred-nanometer size and negatively loaded. 35268609 4 23 theme technology 906:915 arg1 chromatography-quadrupole-time 831:860 ultra-high performance liquid chromatography-quadrupole-time 801:860 ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology 801:915 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 4 23 theme technology 906:915 arg1 spectroscopy 784:795 infrared spectroscopy 775:795 infrared spectroscopy 775:795 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 2 24 theme nanoparticles 447:459 arg1 structure 418:426 structure 418:426 structure 418:426 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 2 24 theme nanoparticles 447:459 arg1 composition 432:442 composition 432:442 composition 432:442 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 3 25 used used 647:650 arg2 method 636:641 the dialysis-centrifugation method 608:641 the dialysis-centrifugation method 608:641 Firstly, the dialysis-centrifugation method was used to separate the nanoparticles and then their size distribution, potential, and morphology were characterized. 35268609 5 26 theme cerebral 1076:1083 arg1 MCAO 1103:1106 MCAO 1103:1106 MCAO 1103:1106 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 5 26 theme cerebral 1076:1083 arg1 occlusion 1092:1100 Middle cerebral artery occlusion 1069:1100 Middle cerebral artery occlusion (MCAO) model 1069:1113 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 4 27 theme flight-mass 865:875 arg1 technology 906:915 flight-mass spectrometer (UPLC-Q-TOF-MS) technology 865:915 flight-mass spectrometer (UPLC-Q-TOF-MS) technology 865:915 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 1 28 theme physical 204:211 arg1 pharmacy 213:220 physical pharmacy 204:220 physical pharmacy 204:220 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 4 29 used used 922:925 arg2 spectroscopy 784:795 infrared spectroscopy 775:795 infrared spectroscopy 775:795 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 4 29 used used 922:925 arg2 chromatography-quadrupole-time 831:860 ultra-high performance liquid chromatography-quadrupole-time 801:860 ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology 801:915 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 5 30 theme Dawley 1019:1024 arg1 rats 1031:1034 Sprague Dawley (SD) rats 1011:1034 Sprague Dawley (SD) rats 1011:1034 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 1 31 theme pharmacy 213:220 arg1 perspective 189:199 a unique perspective 180:199 a unique perspective of physical pharmacy 180:220 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 0 32 theme Nanoparticles 42:54 arg1 Characterization 14:29 Characterization 14:29 Characterization 14:29 Isolation and Characterization of Natural Nanoparticles in Naoluo Xintong Decoction and Their Brain Protection Research. 35268609 0 32 theme Nanoparticles 42:54 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and Characterization of Natural Nanoparticles in Naoluo Xintong Decoction and Their Brain Protection Research. 35268609 0 32 theme Nanoparticles 42:54 arg1 Research 111:118 Their Brain Protection Research 88:118 Their Brain Protection Research 88:118 Isolation and Characterization of Natural Nanoparticles in Naoluo Xintong Decoction and Their Brain Protection Research. 35268609 5 33 theme NLXT-NPs 1207:1214 arg1 groups 1216:1221 NLXT-NPs groups 1207:1221 NLXT-NPs groups 1207:1221 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 9 34 theme essential 1751:1759 arg1 role 1761:1764 an essential role 1748:1764 an essential role 1748:1764 However, removing nanoparticles can significantly reduce the brain-protective effect of NLXT, which indicates that NLXT-NPs play an essential role in the efficacy of NLXT. 35268609 2 35 dep structure 418:426 arg1 the 414:416 the 414:416 the 414:416 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 0 36 theme Natural 34:40 arg1 Nanoparticles 42:54 Natural Nanoparticles 34:54 Natural Nanoparticles 34:54 Isolation and Characterization of Natural Nanoparticles in Naoluo Xintong Decoction and Their Brain Protection Research. 35268609 2 37 theme NLXT 541:544 arg1 related 557:563 related 557:563 related 557:563 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 2 37 theme NLXT 541:544 arg1 effect 531:536 the brain protection effect 510:536 the brain protection effect of NLXT 510:544 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 6 38 theme neurological 1250:1261 arg1 function 1263:1270 the neurological function 1246:1270 the neurological function 1246:1270 After administration, the neurological function, histopathological changes, oxidative stress, and apoptosis level were measured. 35268609 8 39 theme cell 1603:1606 arg1 apoptosis 1608:1616 cell apoptosis 1603:1616 cell apoptosis 1603:1616 NLXT can improve nerve function, reduce oxidative stress, and inhibit cell apoptosis. 35268609 5 40 theme occlusion 1092:1100 arg1 model 1109:1113 Middle cerebral artery occlusion (MCAO) model 1069:1113 Middle cerebral artery occlusion (MCAO) model 1069:1113 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 5 40 theme occlusion 1092:1100 arg1 sham 1063:1066 sham 1063:1066 sham 1063:1066 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 5 41 theme Middle 1069:1074 arg1 MCAO 1103:1106 MCAO 1103:1106 MCAO 1103:1106 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 5 41 theme Middle 1069:1074 arg1 occlusion 1092:1100 Middle cerebral artery occlusion 1069:1100 Middle cerebral artery occlusion (MCAO) model 1069:1113 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 1 42 theme natural 318:324 arg1 nanoparticles 326:338 natural nanoparticles 318:338 natural nanoparticles 318:338 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 5 43 theme artery 1085:1090 arg1 MCAO 1103:1106 MCAO 1103:1106 MCAO 1103:1106 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 5 43 theme artery 1085:1090 arg1 occlusion 1092:1100 Middle cerebral artery occlusion 1069:1100 Middle cerebral artery occlusion (MCAO) model 1069:1113 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 4 44 theme spectrometer 877:888 arg1 technology 906:915 flight-mass spectrometer (UPLC-Q-TOF-MS) technology 865:915 flight-mass spectrometer (UPLC-Q-TOF-MS) technology 865:915 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 4 45 theme liquid 824:829 arg1 chromatography-quadrupole-time 831:860 ultra-high performance liquid chromatography-quadrupole-time 801:860 ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology 801:915 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 0 46 from Research 111:118 arg1 Decoction 74:82 Decoction 74:82 Decoction 74:82 Isolation and Characterization of Natural Nanoparticles in Naoluo Xintong Decoction and Their Brain Protection Research. 35268609 4 47 theme performance 812:822 arg1 chromatography-quadrupole-time 831:860 ultra-high performance liquid chromatography-quadrupole-time 801:860 ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology 801:915 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 9 48 theme removing 1628:1635 arg1 nanoparticles 1637:1649 removing nanoparticles 1628:1649 removing nanoparticles 1628:1649 However, removing nanoparticles can significantly reduce the brain-protective effect of NLXT, which indicates that NLXT-NPs play an essential role in the efficacy of NLXT. 35268609 4 49 theme nanoparticles 957:969 arg1 composition 942:952 the composition 938:952 the composition of nanoparticles 938:969 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 4 50 theme ultra-high 801:810 arg1 chromatography-quadrupole-time 831:860 ultra-high performance liquid chromatography-quadrupole-time 801:860 ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology 801:915 In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. 35268609 2 51 from structure 418:426 arg1 NLXT 480:483 NLXT 480:483 NLXT 480:483 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 2 51 from structure 418:426 arg1 Xintong 471:477 Xintong 471:477 Xintong 471:477 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 5 52 theme pharmacodynamic 983:997 arg1 experiment 999:1008 the pharmacodynamic experiment 979:1008 the pharmacodynamic experiment 979:1008 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 1 53 theme phase 237:241 arg1 composition 243:253 the phase composition 233:253 the phase composition of traditional Chinese medicine (TCM) 233:291 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 9 54 theme NLXT 1785:1788 arg1 efficacy 1773:1780 the efficacy 1769:1780 the efficacy of NLXT 1769:1788 However, removing nanoparticles can significantly reduce the brain-protective effect of NLXT, which indicates that NLXT-NPs play an essential role in the efficacy of NLXT. 35268609 1 55 theme modern 148:153 arg1 techniques 166:175 modern analytical techniques 148:175 modern analytical techniques 148:175 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 5 56 theme removing 1146:1153 arg1 nanoparticles 1132:1144 nanoparticles 1132:1144 nanoparticles removing (NLXT-RN) 1132:1163 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 5 56 theme removing 1146:1153 arg1 NLXT-RN 1156:1162 NLXT-RN 1156:1162 NLXT-RN 1156:1162 As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. 35268609 3 57 theme dialysis-centrifugation 612:634 arg1 method 636:641 the dialysis-centrifugation method 608:641 the dialysis-centrifugation method 608:641 Firstly, the dialysis-centrifugation method was used to separate the nanoparticles and then their size distribution, potential, and morphology were characterized. 35268609 2 58 from composition 432:442 arg1 NLXT 480:483 NLXT 480:483 NLXT 480:483 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 2 58 from composition 432:442 arg1 Xintong 471:477 Xintong 471:477 Xintong 471:477 This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). 35268609 1 59 theme analytical 155:164 arg1 techniques 166:175 modern analytical techniques 148:175 modern analytical techniques 148:175 Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. 35268609 9 60 theme brain-protective 1680:1695 arg1 effect 1697:1702 the brain-protective effect 1676:1702 the brain-protective effect 1676:1702 However, removing nanoparticles can significantly reduce the brain-protective effect of NLXT, which indicates that NLXT-NPs play an essential role in the efficacy of NLXT. 36229526 2 0 theme O-GlcNAc 532:539 arg1 modification 541:552 O-GlcNAc modification 532:552 O-GlcNAc modification (O-GlcNAcylation) 532:570 Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). 36229526 2 0 theme O-GlcNAc 532:539 arg1 O-GlcNAcylation 555:569 O-GlcNAcylation 555:569 O-GlcNAcylation 555:569 Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). 36229526 2 1 from assays 478:483 arg1 cells 496:500 HEK293T cells 488:500 HEK293T cells 488:500 Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). 36229526 1 2 theme beneficial 175:184 arg1 effects 186:192 the beneficial effects 171:192 the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy 171:304 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 0 3 theme mineralocorticoid 14:30 arg1 hypertension 52:63 mineralocorticoid receptor-associated hypertension 14:63 mineralocorticoid receptor-associated hypertension 14:63 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 36229526 8 4 theme diabetes 1548:1555 arg1 mellitus 1557:1564 diabetes mellitus 1548:1564 diabetes mellitus 1548:1564 These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus. 36229526 4 5 theme MR 799:800 arg1 O-GlcNAcylation 776:790 O-GlcNAcylation 776:790 O-GlcNAcylation of the MR at amino acids 295-307 776:823 Liquid chromatography-tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295-307. 36229526 8 6 theme MR 1485:1486 arg1 target 1493:1498 a target 1491:1498 a target for prevention of complications associated with diabetes mellitus 1491:1564 These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus. 36229526 8 6 theme MR 1485:1486 arg1 mechanism 1472:1480 a novel mechanism 1464:1480 a novel mechanism of MR 1464:1486 These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus. 36229526 1 7 theme diabetic 285:292 arg1 nephropathy 294:304 diabetic nephropathy 285:304 diabetic nephropathy 285:304 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 0 8 theme modification 108:119 arg1 role 91:94 the role 87:94 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 0:120 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 36229526 0 9 from Mechanisms 0:9 arg1 mellitus 77:84 diabetes mellitus 68:84 diabetes mellitus 68:84 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 36229526 5 10 dep levels 908:913 arg1 the 896:898 the 896:898 the 896:898 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 1 11 from effects 186:192 arg1 patients 244:251 patients 244:251 patients with resistant hypertension and diabetic nephropathy 244:304 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 5 12 theme mRNA 1091:1094 arg1 levels 1096:1101 increased SGK1 mRNA levels 1076:1101 increased SGK1 mRNA levels 1076:1101 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 0 13 theme O-GlcNAc 99:106 arg1 modification 108:119 O-GlcNAc modification 99:119 O-GlcNAc modification 99:119 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 36229526 7 14 theme transcriptional 1346:1360 arg1 activities 1362:1371 transcriptional activities 1346:1371 transcriptional activities of the receptor 1346:1387 Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. 36229526 3 15 theme transcriptional 599:613 arg1 activities 615:624 transcriptional activities 599:624 transcriptional activities 599:624 The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. 36229526 4 16 theme chromatography-tandem 727:747 arg1 spectrometry 754:765 Liquid chromatography-tandem mass spectrometry 720:765 Liquid chromatography-tandem mass spectrometry 720:765 Liquid chromatography-tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295-307. 36229526 3 17 with parallel 655:662 arg1 O-GlcNAcylation 673:687 its O-GlcNAcylation 669:687 its O-GlcNAcylation under high-glucose conditions 669:717 The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. 36229526 5 18 theme kidneys 968:974 arg1 O-GlcNAcylation 870:884 O-GlcNAcylation 870:884 O-GlcNAcylation 870:884 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 5 18 theme kidneys 968:974 arg1 levels 908:913 protein levels 900:913 protein levels 900:913 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 5 18 theme kidneys 968:974 arg1 activities 935:944 transcriptional activities 919:944 transcriptional activities 919:944 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 3 19 theme expression 577:586 arg1 levels 588:593 The expression levels 573:593 The expression levels 573:593 The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. 36229526 5 20 theme mouse 962:966 arg1 kidneys 968:974 MR. In db/db mouse kidneys 949:974 MR. In db/db mouse kidneys 949:974 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 5 21 theme protein 900:906 arg1 levels 908:913 protein levels 900:913 protein levels 900:913 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 6 22 theme tissue 1194:1199 arg1 levels 1210:1215 tissue O-GlcNAc levels 1194:1215 tissue O-GlcNAc levels 1194:1215 The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. 36229526 5 23 theme increased 1076:1084 arg1 levels 1096:1101 increased SGK1 mRNA levels 1076:1101 increased SGK1 mRNA levels 1076:1101 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 6 24 theme O-GlcNAc 1201:1208 arg1 levels 1210:1215 tissue O-GlcNAc levels 1194:1215 tissue O-GlcNAc levels 1194:1215 The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. 36229526 1 25 theme mineralocorticoid 197:213 arg1 receptor 215:222 mineralocorticoid receptor 197:222 mineralocorticoid receptor (MR) antagonists 197:239 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 1 25 theme mineralocorticoid 197:213 arg1 MR 225:226 MR 225:226 MR 225:226 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 5 26 with parallel 1008:1015 arg1 levels 1039:1044 overall O-GlcNAc levels 1022:1044 overall O-GlcNAc levels of the tissue 1022:1058 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 5 27 dep increased 995:1003 arg1 accompanied 1061:1071 accompanied 1061:1071 accompanied by increased SGK1 mRNA levels 1061:1101 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 7 28 theme receptor 1380:1387 arg1 activities 1362:1371 transcriptional activities 1346:1371 transcriptional activities of the receptor 1346:1387 Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. 36229526 7 28 theme receptor 1380:1387 arg1 levels 1335:1340 protein levels 1327:1340 protein levels 1327:1340 Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. 36229526 1 29 theme receptor 215:222 arg1 antagonists 229:239 mineralocorticoid receptor (MR) antagonists 197:239 mineralocorticoid receptor (MR) antagonists 197:239 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 3 30 theme receptor 633:640 arg1 levels 588:593 The expression levels 573:593 The expression levels 573:593 The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. 36229526 3 30 theme receptor 633:640 arg1 activities 615:624 transcriptional activities 599:624 transcriptional activities 599:624 The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. 36229526 5 31 theme Point 826:830 arg1 mutations 832:840 Point mutations 826:840 Point mutations in those residues 826:858 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 1 32 theme type 439:442 arg1 diabetes 446:453 type 2 diabetes 439:453 type 2 diabetes 439:453 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 0 33 theme receptor-associated 32:50 arg1 hypertension 52:63 mineralocorticoid receptor-associated hypertension 14:63 mineralocorticoid receptor-associated hypertension 14:63 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 36229526 1 34 theme post-translational 319:336 arg1 modification 338:349 post-translational modification 319:349 post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes 319:453 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 2 35 theme HEK293T 488:494 arg1 cells 496:500 HEK293T cells 488:500 HEK293T cells 488:500 Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). 36229526 8 36 theme novel 1466:1470 arg1 target 1493:1498 a target 1491:1498 a target for prevention of complications associated with diabetes mellitus 1491:1564 These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus. 36229526 8 36 theme novel 1466:1470 arg1 mechanism 1472:1480 a novel mechanism 1464:1480 a novel mechanism of MR 1464:1486 These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus. 36229526 5 37 theme tissue 1053:1058 arg1 levels 1039:1044 overall O-GlcNAc levels 1022:1044 overall O-GlcNAc levels of the tissue 1022:1058 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 5 38 theme MR. 949:951 arg1 kidneys 968:974 MR. In db/db mouse kidneys 949:974 MR. In db/db mouse kidneys 949:974 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 7 39 theme high-glucose 1395:1406 arg1 conditions 1408:1417 high-glucose conditions 1395:1417 high-glucose conditions 1395:1417 Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. 36229526 1 40 theme antagonists 229:239 arg1 effects 186:192 the beneficial effects 171:192 the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy 171:304 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 5 41 theme MR 977:978 arg1 levels 988:993 MR protein levels 977:993 MR protein levels 977:993 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 2 42 theme Coimmunoprecipitation 456:476 arg1 assays 478:483 Coimmunoprecipitation assays 456:483 Coimmunoprecipitation assays in HEK293T cells 456:500 Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). 36229526 0 43 theme hypertension 52:63 arg1 Mechanisms 0:9 Mechanisms 0:9 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 0:120 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 36229526 5 44 theme transcriptional 919:933 arg1 activities 935:944 transcriptional activities 919:944 transcriptional activities 919:944 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 4 45 theme Liquid 720:725 arg1 spectrometry 754:765 Liquid chromatography-tandem mass spectrometry 720:765 Liquid chromatography-tandem mass spectrometry 720:765 Liquid chromatography-tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295-307. 36229526 1 46 theme MR 358:359 arg1 modification 338:349 post-translational modification 319:349 post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes 319:453 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 5 47 from mutations 832:840 arg1 residues 851:858 those residues 845:858 those residues 845:858 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 6 48 theme MR 1221:1222 arg1 levels 1232:1237 MR protein levels 1221:1237 MR protein levels 1221:1237 The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. 36229526 6 49 theme db/db 1242:1246 arg1 mice 1248:1251 db/db mice 1242:1251 db/db mice 1242:1251 The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. 36229526 0 50 theme diabetes 68:75 arg1 mellitus 77:84 diabetes mellitus 68:84 diabetes mellitus 68:84 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 36229526 6 51 theme O-GlcNAcylation 1169:1183 arg1 inhibitor 1156:1164 an inhibitor 1153:1164 an inhibitor of O-GlcNAcylation 1153:1183 The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. 36229526 6 51 theme O-GlcNAcylation 1169:1183 arg1 6-diazo-5-oxo-L-norleucin 1126:1150 6-diazo-5-oxo-L-norleucin 1126:1150 6-diazo-5-oxo-L-norleucin 1126:1150 The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. 36229526 4 52 theme amino 805:809 arg1 acids 811:815 amino acids 295-307 805:823 amino acids 295-307 805:823 Liquid chromatography-tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295-307. 36229526 5 53 theme In 953:954 arg1 kidneys 968:974 MR. In db/db mouse kidneys 949:974 MR. In db/db mouse kidneys 949:974 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 8 54 theme complications 1518:1530 arg1 prevention 1504:1513 prevention 1504:1513 prevention of complications associated with diabetes mellitus 1504:1564 These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus. 36229526 5 55 theme SGK1 1086:1089 arg1 levels 1096:1101 increased SGK1 mRNA levels 1076:1101 increased SGK1 mRNA levels 1076:1101 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 5 56 theme overall 1022:1028 arg1 levels 1039:1044 overall O-GlcNAc levels 1022:1044 overall O-GlcNAc levels of the tissue 1022:1058 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 6 57 theme protein 1224:1230 arg1 levels 1232:1237 MR protein levels 1221:1237 MR protein levels 1221:1237 The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. 36229526 6 58 theme 6-diazo-5-oxo-L-norleucin 1126:1150 arg1 administration 1108:1121 The administration 1104:1121 The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, 1104:1184 The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. 36229526 3 59 theme high-glucose 695:706 arg1 conditions 708:717 high-glucose conditions 695:717 high-glucose conditions 695:717 The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. 36229526 5 60 theme O-GlcNAc 1030:1037 arg1 levels 1039:1044 overall O-GlcNAc levels 1022:1044 overall O-GlcNAc levels of the tissue 1022:1058 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 4 61 from acids 811:815 arg1 O-GlcNAcylation 776:790 O-GlcNAcylation 776:790 O-GlcNAcylation of the MR at amino acids 295-307 776:823 Liquid chromatography-tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295-307. 36229526 7 62 theme protein 1327:1333 arg1 levels 1335:1340 protein levels 1327:1340 protein levels 1327:1340 Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. 36229526 5 63 theme db/db 956:960 arg1 kidneys 968:974 MR. In db/db mouse kidneys 949:974 MR. In db/db mouse kidneys 949:974 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 5 64 theme protein 980:986 arg1 levels 988:993 MR protein levels 977:993 MR protein levels 977:993 Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. 36229526 4 65 theme mass 749:752 arg1 spectrometry 754:765 Liquid chromatography-tandem mass spectrometry 720:765 Liquid chromatography-tandem mass spectrometry 720:765 Liquid chromatography-tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295-307. 36229526 1 66 theme resistant 258:266 arg1 hypertension 268:279 resistant hypertension 258:279 resistant hypertension 258:279 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 2 67 theme modification 541:552 arg1 MR 514:515 MR 514:515 MR 514:515 Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). 36229526 2 67 theme modification 541:552 arg1 target 522:527 a target 520:527 a target of O-GlcNAc modification (O-GlcNAcylation) 520:570 Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). 36229526 0 68 dep Mechanisms 0:9 arg1 role 91:94 the role 87:94 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 0:120 Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification. 36229526 1 69 with patients 244:251 arg1 hypertension 268:279 resistant hypertension 258:279 resistant hypertension 258:279 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 1 69 with patients 244:251 arg1 nephropathy 294:304 diabetic nephropathy 285:304 diabetic nephropathy 285:304 This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. 36229526 7 70 theme MR 1305:1306 arg1 O-GlcNAcylation 1282:1296 O-GlcNAcylation 1282:1296 O-GlcNAcylation of the MR 1282:1306 Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. 35575289 0 0 theme spike 71:75 arg1 protein 77:83 SARS-CoV-2 spike protein 60:83 SARS-CoV-2 spike protein 60:83 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 8 1 theme cleavage 1371:1378 arg1 site 1380:1383 the S1/S2 cleavage site 1361:1383 the S1/S2 cleavage site 1361:1383 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 4 2 theme host 646:649 arg1 proteases 651:659 host proteases 646:659 host proteases 646:659 The biochemical basis for the differences in interactions with host proteases for the VOC/VOI spike proteins has not yet been explored. 35575289 6 3 theme furin 953:957 arg1 protease 959:966 the furin protease 949:966 the furin protease but not TMPRSS2 949:982 All mutations found at the S1/S2 sites were predicted to increase affinity to the furin protease but not TMPRSS2. 35575289 0 4 theme SARS-CoV-2 60:69 arg1 protein 77:83 SARS-CoV-2 spike protein 60:83 SARS-CoV-2 spike protein 60:83 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 7 5 theme Delta 1059:1063 arg1 strain 1065:1070 the Delta strain 1055:1070 the Delta strain 1055:1070 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 10 6 from effect 1689:1694 arg1 sites 1782:1786 SARS-CoV-2 spike protein cleavage sites 1748:1786 SARS-CoV-2 spike protein cleavage sites 1748:1786 Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites. 35575289 2 7 theme concern 352:358 arg1 variants 340:347 variants 340:347 variants of concern (VOC) 340:364 Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. 35575289 2 7 theme concern 352:358 arg1 VOI 392:394 VOI 392:394 VOI 392:394 Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. 35575289 2 7 theme concern 352:358 arg1 VOC 361:363 VOC 361:363 VOC 361:363 Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. 35575289 2 7 theme concern 352:358 arg1 variants 370:377 variants 370:377 variants of interest (VOI) 370:395 Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. 35575289 7 8 theme phosphorylation 1129:1143 arg1 motif 1145:1149 a proline-directed kinase phosphorylation motif 1103:1149 a proline-directed kinase phosphorylation motif 1103:1149 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 9 9 dep hinder 1475:1480 arg1 decrease 1519:1526 decrease 1519:1526 decrease syncytia formation 1519:1545 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 9 9 dep hinder 1475:1480 arg1 induce 1551:1556 induce 1551:1556 induce cell entry through the endocytic pathway as has been shown in previous studies 1551:1635 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 9 10 theme cell 1558:1561 arg1 entry 1563:1567 cell entry 1558:1567 cell entry 1558:1567 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 9 11 theme Omicron 1456:1462 arg1 strain 1464:1469 the Omicron strain 1452:1469 the Omicron strain 1452:1469 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 7 12 from P681 1016:1019 arg1 Mutations 985:993 Mutations 985:993 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, 985:1071 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 7 12 from P681 1016:1019 arg1 strains 1032:1038 several strains 1024:1038 several strains 1024:1038 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 7 13 theme kinase 1122:1127 arg1 motif 1145:1149 a proline-directed kinase phosphorylation motif 1103:1149 a proline-directed kinase phosphorylation motif 1103:1149 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 9 14 gly glycosylation 1435:1447 arg1 strain 1464:1469 the Omicron strain 1452:1469 the Omicron strain 1452:1469 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 8 15 theme N679K 1257:1261 arg1 mutation 1263:1270 the unique N679K mutation 1246:1270 the unique N679K mutation in the Omicron strain 1246:1292 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 5 16 theme structural 851:860 arg1 effects 862:868 their structural effects 845:868 their structural effects 845:868 Using sequence and structure-based bioinformatics, mutations near the VOC/VOI spike protein cleavage sites were inspected for their structural effects. 35575289 4 17 from differences 613:623 arg1 interactions 628:639 interactions 628:639 interactions with host proteases for the VOC/VOI spike proteins 628:690 The biochemical basis for the differences in interactions with host proteases for the VOC/VOI spike proteins has not yet been explored. 35575289 5 18 theme cleavage 811:818 arg1 sites 820:824 the VOC/VOI spike protein cleavage sites 785:824 the VOC/VOI spike protein cleavage sites 785:824 Using sequence and structure-based bioinformatics, mutations near the VOC/VOI spike protein cleavage sites were inspected for their structural effects. 35575289 5 19 theme spike 797:801 arg1 sites 820:824 the VOC/VOI spike protein cleavage sites 785:824 the VOC/VOI spike protein cleavage sites 785:824 Using sequence and structure-based bioinformatics, mutations near the VOC/VOI spike protein cleavage sites were inspected for their structural effects. 35575289 7 20 from disruption 1089:1098 arg1 site 1164:1167 the S1/S2 site 1154:1167 the S1/S2 site 1154:1167 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 6 21 located found 885:889 arg1 sites 904:908 the S1/S2 sites 894:908 the S1/S2 sites 894:908 All mutations found at the S1/S2 sites were predicted to increase affinity to the furin protease but not TMPRSS2. 35575289 6 21 located found 885:889 arg2 mutations 875:883 All mutations 871:883 All mutations found at the S1/S2 sites 871:908 All mutations found at the S1/S2 sites were predicted to increase affinity to the furin protease but not TMPRSS2. 35575289 10 22 theme experimental 1646:1657 arg1 work 1659:1662 Further experimental work 1638:1662 Further experimental work 1638:1662 Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites. 35575289 8 23 from mutation 1263:1270 arg1 strain 1287:1292 the Omicron strain 1275:1292 the Omicron strain 1275:1292 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 2 24 theme interest 382:389 arg1 variants 340:347 variants 340:347 variants of concern (VOC) 340:364 Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. 35575289 2 24 theme interest 382:389 arg1 VOI 392:394 VOI 392:394 VOI 392:394 Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. 35575289 2 24 theme interest 382:389 arg1 VOC 361:363 VOC 361:363 VOC 361:363 Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. 35575289 2 24 theme interest 382:389 arg1 variants 370:377 variants 370:377 variants of interest (VOI) 370:395 Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. 35575289 0 25 theme increased 93:101 arg1 propensity 103:112 increased propensity 93:112 increased propensity of glycosylation 93:129 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 4 26 with interactions 628:639 arg1 proteases 651:659 host proteases 646:659 host proteases 646:659 The biochemical basis for the differences in interactions with host proteases for the VOC/VOI spike proteins has not yet been explored. 35575289 7 27 theme such 1041:1044 arg1 P681 1016:1019 the spike residue P681 998:1019 the spike residue P681 in several strains 998:1038 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 7 27 theme such 1041:1044 arg1 P681R 1046:1050 such P681R 1041:1050 such P681R in the Delta strain 1041:1070 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 0 28 theme In 0:1 arg1 analysis 10:17 In silico analysis 0:17 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein 0:83 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 1 29 theme severe 166:171 arg1 syndrome 185:192 the severe respiratory syndrome 162:192 the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein 162:233 Cleavage of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. 35575289 8 30 link O-linked 1335:1342 arg1 glycosylation 1344:1356 O-linked glycosylation 1335:1356 O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases 1335:1427 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 7 31 theme several 1024:1030 arg1 strains 1032:1038 several strains 1024:1038 several strains 1024:1038 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 8 32 from site 1380:1383 arg1 glycosylation 1344:1356 O-linked glycosylation 1335:1356 O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases 1335:1427 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 9 33 theme endocytic 1581:1589 arg1 pathway 1591:1597 the endocytic pathway 1577:1597 the endocytic pathway as has been shown in previous studies 1577:1635 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 1 34 theme respiratory 173:183 arg1 syndrome 185:192 the severe respiratory syndrome 162:192 the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein 162:233 Cleavage of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. 35575289 2 35 theme fusion 421:426 arg1 capacity 428:435 membrane fusion capacity 412:435 membrane fusion capacity 412:435 Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. 35575289 1 36 theme viral-cell 274:283 arg1 fusion 285:290 viral-cell fusion 274:290 viral-cell fusion 274:290 Cleavage of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. 35575289 3 37 theme host 531:534 arg1 proteases 536:544 host proteases 531:544 host proteases 531:544 Mutations near cleavage motifs, such as the S1/S2 and S2' sites, may alter interactions with host proteases and, thus, the potential for fusion. 35575289 1 38 theme syndrome 185:192 arg1 protein 227:233 the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein 162:233 the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein 162:233 Cleavage of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. 35575289 2 39 theme membrane 412:419 arg1 capacity 428:435 membrane fusion capacity 412:435 membrane fusion capacity 412:435 Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. 35575289 10 40 theme modifications 1731:1743 arg1 effect 1689:1694 the effect 1685:1694 the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites 1685:1786 Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites. 35575289 0 41 theme glycosylation 117:129 arg1 propensity 103:112 increased propensity 93:112 increased propensity of glycosylation 93:129 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 9 42 from glycosylation 1435:1447 arg1 strain 1464:1469 the Omicron strain 1452:1469 the Omicron strain 1452:1469 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 4 43 theme spike 677:681 arg1 proteins 683:690 the VOC/VOI spike proteins 665:690 the VOC/VOI spike proteins 665:690 The biochemical basis for the differences in interactions with host proteases for the VOC/VOI spike proteins has not yet been explored. 35575289 7 44 theme spike 1002:1006 arg1 P681 1016:1019 the spike residue P681 998:1019 the spike residue P681 in several strains 998:1038 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 7 44 theme spike 1002:1006 arg1 P681R 1046:1050 such P681R 1041:1050 such P681R in the Delta strain 1041:1070 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 8 45 theme S1/S2 1365:1369 arg1 site 1380:1383 the S1/S2 cleavage site 1361:1383 the S1/S2 cleavage site 1361:1383 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 9 46 theme cell 1495:1498 arg1 surface 1500:1506 the cell surface 1491:1506 the cell surface 1491:1506 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 9 47 from surface 1500:1506 arg1 entry 1482:1486 entry 1482:1486 entry at the cell surface 1482:1506 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 3 48 theme cleavage 453:460 arg1 motifs 462:467 cleavage motifs 453:467 cleavage motifs 453:467 Mutations near cleavage motifs, such as the S1/S2 and S2' sites, may alter interactions with host proteases and, thus, the potential for fusion. 35575289 3 48 theme cleavage 453:460 arg1 sites 496:500 the S1/S2 and S2' sites 478:500 the S1/S2 and S2' sites 478:500 Mutations near cleavage motifs, such as the S1/S2 and S2' sites, may alter interactions with host proteases and, thus, the potential for fusion. 35575289 1 49 theme syncytia 296:303 arg1 formation 305:313 syncytia formation 296:313 syncytia formation 296:313 Cleavage of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. 35575289 0 50 theme Omicron 134:140 arg1 strain 142:147 Omicron strain 134:147 Omicron strain 134:147 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 3 51 with interactions 513:524 arg1 proteases 536:544 host proteases 531:544 host proteases 531:544 Mutations near cleavage motifs, such as the S1/S2 and S2' sites, may alter interactions with host proteases and, thus, the potential for fusion. 35575289 4 52 theme biochemical 587:597 arg1 basis 599:603 The biochemical basis 583:603 The biochemical basis for the differences in interactions with host proteases for the VOC/VOI spike proteins 583:690 The biochemical basis for the differences in interactions with host proteases for the VOC/VOI spike proteins has not yet been explored. 35575289 0 53 theme mutations 22:30 arg1 analysis 10:17 In silico analysis 0:17 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein 0:83 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 7 54 from P681R 1046:1050 arg1 strain 1065:1070 the Delta strain 1055:1070 the Delta strain 1055:1070 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 7 55 theme residue 1008:1014 arg1 P681 1016:1019 the spike residue P681 998:1019 the spike residue P681 in several strains 998:1038 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 7 55 theme residue 1008:1014 arg1 P681R 1046:1050 such P681R 1041:1050 such P681R in the Delta strain 1041:1070 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 10 56 theme protein 1765:1771 arg1 sites 1782:1786 SARS-CoV-2 spike protein cleavage sites 1748:1786 SARS-CoV-2 spike protein cleavage sites 1748:1786 Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites. 35575289 10 57 theme mutations 1699:1707 arg1 effect 1689:1694 the effect 1685:1694 the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites 1685:1786 Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites. 35575289 5 58 theme protein 803:809 arg1 sites 820:824 the VOC/VOI spike protein cleavage sites 785:824 the VOC/VOI spike protein cleavage sites 785:824 Using sequence and structure-based bioinformatics, mutations near the VOC/VOI spike protein cleavage sites were inspected for their structural effects. 35575289 0 59 theme cleavage 43:50 arg1 site 52:55 S1/S2 cleavage site 37:55 S1/S2 cleavage site in SARS-CoV-2 spike protein 37:83 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 6 60 theme S1/S2 898:902 arg1 sites 904:908 the S1/S2 sites 894:908 the S1/S2 sites 894:908 All mutations found at the S1/S2 sites were predicted to increase affinity to the furin protease but not TMPRSS2. 35575289 5 61 theme structure-based 738:752 arg1 bioinformatics 754:767 structure-based bioinformatics 738:767 structure-based bioinformatics 738:767 Using sequence and structure-based bioinformatics, mutations near the VOC/VOI spike protein cleavage sites were inspected for their structural effects. 35575289 0 62 from site 52:55 arg1 protein 77:83 SARS-CoV-2 spike protein 60:83 SARS-CoV-2 spike protein 60:83 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 8 63 theme Omicron 1279:1285 arg1 strain 1287:1292 the Omicron strain 1275:1292 the Omicron strain 1275:1292 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 10 64 theme cleavage 1773:1780 arg1 sites 1782:1786 SARS-CoV-2 spike protein cleavage sites 1748:1786 SARS-CoV-2 spike protein cleavage sites 1748:1786 Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites. 35575289 0 65 theme S1/S2 37:41 arg1 site 52:55 S1/S2 cleavage site 37:55 S1/S2 cleavage site in SARS-CoV-2 spike protein 37:83 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 9 66 theme previous 1620:1627 arg1 studies 1629:1635 previous studies 1620:1635 previous studies 1620:1635 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 7 67 theme phosphorylation 1201:1215 arg1 impact 1191:1196 the impact 1187:1196 the impact of phosphorylation for these variants 1187:1234 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 9 68 dep pathway 1591:1597 arg1 shown 1611:1615 shown 1611:1615 has been shown in previous studies 1602:1635 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 10 69 theme posttranslational 1713:1729 arg1 modifications 1731:1743 posttranslational modifications 1713:1743 posttranslational modifications 1713:1743 Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites. 35575289 10 70 theme SARS-CoV-2 1748:1757 arg1 sites 1782:1786 SARS-CoV-2 spike protein cleavage sites 1748:1786 SARS-CoV-2 spike protein cleavage sites 1748:1786 Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites. 35575289 8 71 theme O-linked 1335:1342 arg1 glycosylation 1344:1356 O-linked glycosylation 1335:1356 O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases 1335:1427 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 1 72 theme spike 221:225 arg1 protein 227:233 the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein 162:233 the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein 162:233 Cleavage of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. 35575289 10 73 theme Further 1638:1644 arg1 work 1659:1662 Further experimental work 1638:1662 Further experimental work 1638:1662 Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites. 35575289 8 74 theme unique 1250:1255 arg1 mutation 1263:1270 the unique N679K mutation 1246:1270 the unique N679K mutation in the Omicron strain 1246:1292 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 1 75 theme protein 227:233 arg1 Cleavage 150:157 Cleavage 150:157 Cleavage of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein 150:233 Cleavage of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. 35575289 7 76 theme S1/S2 1158:1162 arg1 site 1164:1167 the S1/S2 site 1154:1167 the S1/S2 site 1154:1167 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 7 77 from site 1164:1167 arg1 disruption 1089:1098 the disruption 1085:1098 the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants 1085:1234 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 7 77 from site 1164:1167 arg1 motif 1145:1149 a proline-directed kinase phosphorylation motif 1103:1149 a proline-directed kinase phosphorylation motif 1103:1149 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 9 78 theme syncytia 1528:1535 arg1 formation 1537:1545 syncytia formation 1528:1545 syncytia formation 1528:1545 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 9 79 theme Such 1430:1433 arg1 glycosylation 1435:1447 Such glycosylation 1430:1447 Such glycosylation in the Omicron strain 1430:1469 Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. 35575289 8 80 gly glycosylation 1344:1356 arg1 site 1380:1383 the S1/S2 cleavage site 1361:1383 the S1/S2 cleavage site 1361:1383 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 8 80 gly glycosylation 1344:1356 arg2 site 1380:1383 the S1/S2 cleavage site 1361:1383 the S1/S2 cleavage site 1361:1383 However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. 35575289 7 81 theme proline-directed 1105:1120 arg1 motif 1145:1149 a proline-directed kinase phosphorylation motif 1103:1149 a proline-directed kinase phosphorylation motif 1103:1149 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 35575289 0 82 dep In 0:1 arg1 silico 3:8 silico 3:8 silico 3:8 In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain. 35575289 10 83 theme spike 1759:1763 arg1 sites 1782:1786 SARS-CoV-2 spike protein cleavage sites 1748:1786 SARS-CoV-2 spike protein cleavage sites 1748:1786 Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites. 35575289 7 84 theme motif 1145:1149 arg1 disruption 1089:1098 the disruption 1085:1098 the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants 1085:1234 Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. 34978456 0 0 theme O-Linked 87:94 arg1 Strategy 118:125 a Removable O-Linked β-N-Acetylglucosamine Strategy 75:125 a Removable O-Linked β-N-Acetylglucosamine Strategy 75:125 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 34978456 1 1 theme tool 175:178 arg1 molecules 180:188 tool molecules 175:188 tool molecules 175:188 Disulfide-rich proteins are useful as drugs or tool molecules in biomedical studies, but their synthesis is complicated by the difficulties associated with their folding. 34978456 0 2 theme Removable 77:85 arg1 Strategy 118:125 a Removable O-Linked β-N-Acetylglucosamine Strategy 75:125 a Removable O-Linked β-N-Acetylglucosamine Strategy 75:125 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 34978456 5 3 theme homodimer 1073:1081 arg1 interleukin-5 1042:1054 correctly folded interleukin-5 1025:1054 correctly folded interleukin-5 (IL-5) 1025:1061 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 3 theme homodimer 1073:1081 arg1 cytokine 1083:1090 a 26 kDa homodimer cytokine 1064:1090 a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation 1064:1144 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 4 theme iron-regulating 929:943 arg1 hormone 945:951 an iron-regulating hormone 926:951 an iron-regulating hormone bearing four pairs of disulfide-bonds 926:989 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 3 5 theme O-linked 538:545 arg1 groups 580:585 simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups 531:585 simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups 531:585 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 5 6 theme disulfide-bonds 975:989 arg1 pairs 966:970 four pairs 961:970 four pairs of disulfide-bonds 961:989 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 7 theme folded 1035:1040 arg1 interleukin-5 1042:1054 correctly folded interleukin-5 1025:1054 correctly folded interleukin-5 (IL-5) 1025:1061 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 7 theme folded 1035:1040 arg1 cytokine 1083:1090 a 26 kDa homodimer cytokine 1064:1090 a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation 1064:1144 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 7 theme folded 1035:1040 arg1 IL-5 1057:1060 IL-5 1057:1060 IL-5 1057:1060 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 1 8 from molecules 180:188 arg1 studies 204:210 biomedical studies 193:210 biomedical studies 193:210 Disulfide-rich proteins are useful as drugs or tool molecules in biomedical studies, but their synthesis is complicated by the difficulties associated with their folding. 34978456 3 9 theme groups 580:585 arg1 introduction 515:526 the introduction 511:526 the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates 511:718 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 3 10 theme Ser/Thr 594:600 arg1 sites 602:606 the Ser/Thr sites 590:606 the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates 590:718 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 0 11 theme β-N-Acetylglucosamine 96:116 arg1 Strategy 118:125 a Removable O-Linked β-N-Acetylglucosamine Strategy 75:125 a Removable O-Linked β-N-Acetylglucosamine Strategy 75:125 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 34978456 5 12 theme total 1006:1010 arg1 synthesis 1012:1020 the first total synthesis 996:1020 the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation 996:1144 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 1 13 from drugs 166:170 arg1 studies 204:210 biomedical studies 193:210 biomedical studies 193:210 Disulfide-rich proteins are useful as drugs or tool molecules in biomedical studies, but their synthesis is complicated by the difficulties associated with their folding. 34978456 3 14 theme simple 531:536 arg1 groups 580:585 simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups 531:585 simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups 531:585 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 4 15 theme O-GlcNAc 740:747 arg1 groups 749:754 the O-GlcNAc groups 736:754 the O-GlcNAc groups 736:754 After folding, the O-GlcNAc groups can be efficiently removed using O-GlcNAcase (OGA) to afford the correctly folded proteins. 34978456 3 16 theme O-GlcNAc 570:577 arg1 groups 580:585 simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups 531:585 simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups 531:585 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 2 17 theme interchain 460:469 arg1 bonds 481:485 multiple or even interchain disulfide bonds 443:485 multiple or even interchain disulfide bonds 443:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 1 18 theme biomedical 193:202 arg1 studies 204:210 biomedical studies 193:210 biomedical studies 193:210 Disulfide-rich proteins are useful as drugs or tool molecules in biomedical studies, but their synthesis is complicated by the difficulties associated with their folding. 34978456 0 19 theme Chemical 6:13 arg1 Synthesis 15:23 Total Chemical Synthesis 0:23 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 0:126 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 34978456 2 20 theme glycosylation 329:341 arg1 strategy 362:369 a removable glycosylation modification (RGM) strategy 317:369 a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds 317:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 5 21 theme folded 909:914 arg1 hepcidin 916:923 correctly folded hepcidin 899:923 correctly folded hepcidin 899:923 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 0 22 theme Total 0:4 arg1 Synthesis 15:23 Total Chemical Synthesis 0:23 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 0:126 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 34978456 2 23 theme removable 319:327 arg1 strategy 362:369 a removable glycosylation modification (RGM) strategy 317:369 a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds 317:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 2 24 theme chemical 390:397 arg1 synthesis 399:407 the chemical synthesis 386:407 the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds 386:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 2 25 theme even 455:458 arg1 bonds 481:485 multiple or even interchain disulfide bonds 443:485 multiple or even interchain disulfide bonds 443:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 2 26 theme multiple 443:450 arg1 bonds 481:485 multiple or even interchain disulfide bonds 443:485 multiple or even interchain disulfide bonds 443:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 3 27 link O-linked 538:545 arg1 groups 580:585 simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups 531:585 simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups 531:585 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 5 28 theme responsible 1092:1102 arg1 interleukin-5 1042:1054 correctly folded interleukin-5 1025:1054 correctly folded interleukin-5 (IL-5) 1025:1061 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 28 theme responsible 1092:1102 arg1 cytokine 1083:1090 a 26 kDa homodimer cytokine 1064:1090 a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation 1064:1144 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 1 29 theme Disulfide-rich 128:141 arg1 proteins 143:150 Disulfide-rich proteins 128:150 Disulfide-rich proteins 128:150 Disulfide-rich proteins are useful as drugs or tool molecules in biomedical studies, but their synthesis is complicated by the difficulties associated with their folding. 34978456 0 30 theme Folded 38:43 arg1 Proteins 60:67 Correctly Folded Disulfide-Rich Proteins 28:67 Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy 28:125 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 34978456 3 31 theme folding 698:704 arg1 intermediates 706:718 their folding intermediates 692:718 their folding intermediates 692:718 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 5 32 theme hepcidin 916:923 arg1 hormone 945:951 an iron-regulating hormone 926:951 an iron-regulating hormone bearing four pairs of disulfide-bonds 926:989 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 32 theme hepcidin 916:923 arg1 synthesis 886:894 the synthesis 882:894 the synthesis of correctly folded hepcidin 882:923 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 32 theme hepcidin 916:923 arg1 synthesis 1012:1020 the first total synthesis 996:1020 the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation 996:1144 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 2 33 theme proteins 429:436 arg1 synthesis 399:407 the chemical synthesis 386:407 the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds 386:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 5 34 theme eosinophil 1108:1117 arg1 growth 1119:1124 eosinophil growth 1108:1124 eosinophil growth 1108:1124 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 2 35 theme folded 422:427 arg1 proteins 429:436 correctly folded proteins 412:436 correctly folded proteins 412:436 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 0 36 theme Proteins 60:67 arg1 Synthesis 15:23 Total Chemical Synthesis 0:23 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 0:126 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 34978456 0 37 theme Disulfide-Rich 45:58 arg1 Proteins 60:67 Correctly Folded Disulfide-Rich Proteins 28:67 Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy 28:125 Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy. 34978456 5 38 theme 26 1066:1067 arg1 kDa 1069:1071 kDa 1069:1071 kDa 1069:1071 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 39 theme kDa 1069:1071 arg1 interleukin-5 1042:1054 correctly folded interleukin-5 1025:1054 correctly folded interleukin-5 (IL-5) 1025:1061 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 39 theme kDa 1069:1071 arg1 cytokine 1083:1090 a 26 kDa homodimer cytokine 1064:1090 a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation 1064:1144 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 2 40 theme RGM 357:359 arg1 strategy 362:369 a removable glycosylation modification (RGM) strategy 317:369 a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds 317:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 4 41 theme folded 831:836 arg1 proteins 838:845 the correctly folded proteins 817:845 the correctly folded proteins 817:845 After folding, the O-GlcNAc groups can be efficiently removed using O-GlcNAcase (OGA) to afford the correctly folded proteins. 34978456 3 42 theme proteins 663:670 arg1 folding 637:643 the folding 633:643 the folding of disulfide-rich proteins 633:670 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 3 43 theme intermediates 706:718 arg1 stabilization 675:687 stabilization 675:687 stabilization of their folding intermediates 675:718 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 5 44 theme first 1000:1004 arg1 synthesis 1012:1020 the first total synthesis 996:1020 the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation 996:1144 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 2 45 theme modification 343:354 arg1 strategy 362:369 a removable glycosylation modification (RGM) strategy 317:369 a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds 317:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 3 46 from sites 602:606 arg1 introduction 515:526 the introduction 511:526 the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates 511:718 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 5 47 theme interleukin-5 1042:1054 arg1 hormone 945:951 an iron-regulating hormone 926:951 an iron-regulating hormone bearing four pairs of disulfide-bonds 926:989 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 47 theme interleukin-5 1042:1054 arg1 synthesis 886:894 the synthesis 882:894 the synthesis of correctly folded hepcidin 882:923 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 5 47 theme interleukin-5 1042:1054 arg1 synthesis 1012:1020 the first total synthesis 996:1020 the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation 996:1144 Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation. 34978456 3 48 theme β-N-acetylglucosamine 547:567 arg1 groups 580:585 simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups 531:585 simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups 531:585 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 2 49 with synthesis 399:407 arg1 bonds 481:485 multiple or even interchain disulfide bonds 443:485 multiple or even interchain disulfide bonds 443:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 34978456 3 50 theme disulfide-rich 648:661 arg1 proteins 663:670 disulfide-rich proteins 648:670 disulfide-rich proteins 648:670 Our strategy comprises the introduction of simple O-linked β-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. 34978456 2 51 theme disulfide 471:479 arg1 bonds 481:485 multiple or even interchain disulfide bonds 443:485 multiple or even interchain disulfide bonds 443:485 Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. 36187995 6 0 theme HW 769:770 arg1 groups 779:784 the HW and LW groups 765:784 the HW and LW groups 765:784 The core phyla of the HW and LW groups were both Firmicutes and Bacteroidetes. 36187995 3 1 theme body 412:415 arg1 weight 417:422 low body weight 408:422 low body weight group (LW) 408:433 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 10 2 theme black 1665:1669 arg1 goats 1671:1675 Hainan black goats 1658:1675 Hainan black goats with different body weights 1658:1703 The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth. 36187995 0 3 theme black 66:70 arg1 goats 72:76 Hainan black goats 59:76 Hainan black goats 59:76 Association between body weight and distal gut microbes in Hainan black goats at weaning age. 36187995 10 4 theme body 1692:1695 arg1 weights 1697:1703 different body weights 1682:1703 different body weights 1682:1703 The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth. 36187995 9 5 theme HW 1448:1449 arg1 group 1451:1455 the HW group 1444:1455 the HW group 1444:1455 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 3 6 theme weight 417:422 arg1 LW 431:432 LW 431:432 LW 431:432 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 3 6 theme weight 417:422 arg1 group 424:428 low body weight group 408:428 low body weight group (LW) 408:433 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 9 7 theme Differential 1280:1291 arg1 analysis 1293:1300 Differential analysis 1280:1300 Differential analysis of the KEGG pathway 1280:1320 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 3 8 theme weaned 303:308 arg1 lambs 310:314 12 three-month-old weaned lambs 284:314 12 three-month-old weaned lambs with the same birth date 284:339 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 9 9 theme pathway 1314:1320 arg1 analysis 1293:1300 Differential analysis 1280:1300 Differential analysis of the KEGG pathway 1280:1320 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 2 10 theme young 243:247 arg1 goats 262:266 young Hainan black goats 243:266 young Hainan black goats 243:266 However, there are few studies on the gut microbiota of young Hainan black goats. 36187995 8 11 theme body 1236:1239 arg1 weight 1241:1246 body weight 1236:1246 body weight 1236:1246 In addition, genera such as Ruminococcus and Anaerotruncus, which were positively correlated with body weight, were enriched in the HW group; those genera, such as Akkermansia and Christensenellaceae, which were negatively correlated with body weight, were enriched in the LW group. 36187995 9 12 theme Carbohydrate 1376:1387 arg1 Metabolism 1389:1398 Carbohydrate Metabolism 1376:1398 Carbohydrate Metabolism 1376:1398 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 9 13 theme Lipid 1498:1502 arg1 Metabolism 1504:1513 Lipid Metabolism 1498:1513 Lipid Metabolism 1498:1513 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 9 14 theme Acid 1340:1343 arg1 Metabolism 1345:1354 Amino Acid Metabolism 1334:1354 Amino Acid Metabolism 1334:1354 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 4 15 theme predicted 478:486 arg1 function 488:495 predicted function 478:495 predicted function 478:495 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 9 16 theme LW 1576:1577 arg1 group 1579:1583 the LW group 1572:1583 the LW group 1572:1583 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 4 17 theme 16S 591:593 arg1 rRNA 595:598 16S rRNA 591:598 sequencing the 16S rRNA V3-V4 region 576:611 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 7 18 theme group 990:994 arg1 UCG-005 843:849 UCG-005 843:849 UCG-005 843:849 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 18 theme group 990:994 arg1 Akkermansia 948:958 Akkermansia 948:958 Akkermansia 948:958 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 18 theme group 990:994 arg1 genera 881:886 the core genera 872:886 the core genera of the HW group 872:902 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 18 theme group 990:994 arg1 Bacteroides 909:919 Bacteroides 909:919 Bacteroides 909:919 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 18 theme group 990:994 arg1 Escherichia-Shigella 922:941 Escherichia-Shigella 922:941 Escherichia-Shigella 922:941 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 18 theme group 990:994 arg1 Bacteroides 856:866 Bacteroides 856:866 Bacteroides 856:866 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 18 theme group 990:994 arg1 genera 973:978 the core genera 964:978 the core genera of the LW group 964:994 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 18 theme group 990:994 arg1 Parabacteroides 826:840 Parabacteroides 826:840 Parabacteroides 826:840 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 4 19 theme HW 513:514 arg1 feces 504:508 the feces 500:508 the feces of HW and LW groups 500:528 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 1 20 theme healthy 138:144 arg1 growth 146:151 healthy growth 138:151 healthy growth 138:151 Gut microbiota plays a critical role in the healthy growth and development of young animals. 36187995 3 21 theme three-month-old 287:301 arg1 lambs 310:314 12 three-month-old weaned lambs 284:314 12 three-month-old weaned lambs with the same birth date 284:339 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 9 22 theme Cellular 1464:1471 arg1 Processes 1473:1481 Cellular Processes 1464:1481 Cellular Processes 1464:1481 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 2 23 theme gut 225:227 arg1 microbiota 229:238 the gut microbiota 221:238 the gut microbiota of young Hainan black goats 221:266 However, there are few studies on the gut microbiota of young Hainan black goats. 36187995 3 24 theme high 376:379 arg1 HW 400:401 HW 400:401 HW 400:401 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 3 24 theme high 376:379 arg1 group 393:397 the high body weight group 372:397 the high body weight group (HW) 372:402 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 3 25 theme same 325:328 arg1 date 336:339 the same birth date 321:339 the same birth date 321:339 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 5 26 theme HW 645:646 arg1 group 648:652 the HW group 641:652 the HW group 641:652 The results indicated that the HW group exhibited higher community diversity compared with the LW group, based on the Shannon index. 36187995 9 27 theme Energy 1357:1362 arg1 Metabolism 1364:1373 Energy Metabolism 1357:1373 Energy Metabolism 1357:1373 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 6 28 theme core 751:754 arg1 phyla 756:760 The core phyla 747:760 The core phyla of the HW and LW groups 747:784 The core phyla of the HW and LW groups were both Firmicutes and Bacteroidetes. 36187995 6 28 theme core 751:754 arg1 Firmicutes 796:805 Firmicutes 796:805 Firmicutes 796:805 The core phyla of the HW and LW groups were both Firmicutes and Bacteroidetes. 36187995 5 29 theme Shannon 732:738 arg1 index 740:744 the Shannon index 728:744 the Shannon index 728:744 The results indicated that the HW group exhibited higher community diversity compared with the LW group, based on the Shannon index. 36187995 3 30 theme birth 330:334 arg1 date 336:339 the same birth date 321:339 the same birth date 321:339 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 10 31 theme Hainan 1658:1663 arg1 goats 1671:1675 Hainan black goats 1658:1675 Hainan black goats with different body weights 1658:1703 The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth. 36187995 2 32 theme goats 262:266 arg1 microbiota 229:238 the gut microbiota 221:238 the gut microbiota of young Hainan black goats 221:266 However, there are few studies on the gut microbiota of young Hainan black goats. 36187995 2 33 from studies 210:216 arg1 microbiota 229:238 the gut microbiota 221:238 the gut microbiota of young Hainan black goats 221:266 However, there are few studies on the gut microbiota of young Hainan black goats. 36187995 4 34 from diversity 450:458 arg1 feces 504:508 the feces 500:508 the feces of HW and LW groups 500:528 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 4 35 theme microbial 440:448 arg1 diversity 450:458 The microbial diversity 436:458 The microbial diversity 436:458 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 4 36 dep HW 513:514 arg1 groups 523:528 groups 523:528 groups 523:528 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 2 37 theme black 256:260 arg1 goats 262:266 young Hainan black goats 243:266 young Hainan black goats 243:266 However, there are few studies on the gut microbiota of young Hainan black goats. 36187995 5 38 theme LW 709:710 arg1 group 712:716 the LW group 705:716 the LW group 705:716 The results indicated that the HW group exhibited higher community diversity compared with the LW group, based on the Shannon index. 36187995 0 39 theme body 20:23 arg1 weight 25:30 body weight 20:30 body weight 20:30 Association between body weight and distal gut microbes in Hainan black goats at weaning age. 36187995 10 40 theme dominant 1739:1746 arg1 flora 1748:1752 the dominant flora 1735:1752 the dominant flora that contributed to their growth 1735:1785 The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth. 36187995 10 41 with goats 1671:1675 arg1 weights 1697:1703 different body weights 1682:1703 different body weights 1682:1703 The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth. 36187995 2 42 theme Hainan 249:254 arg1 goats 262:266 young Hainan black goats 243:266 young Hainan black goats 243:266 However, there are few studies on the gut microbiota of young Hainan black goats. 36187995 1 43 theme young 172:176 arg1 animals 178:184 young animals 172:184 young animals 172:184 Gut microbiota plays a critical role in the healthy growth and development of young animals. 36187995 0 44 theme distal 36:41 arg1 gut 43:45 distal gut 36:45 distal gut 36:45 Association between body weight and distal gut microbes in Hainan black goats at weaning age. 36187995 7 45 theme HW 895:896 arg1 group 898:902 the HW group 891:902 the HW group 891:902 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 1 46 theme animals 178:184 arg1 development 157:167 development 157:167 development 157:167 Gut microbiota plays a critical role in the healthy growth and development of young animals. 36187995 1 46 theme animals 178:184 arg1 growth 146:151 healthy growth 138:151 healthy growth 138:151 Gut microbiota plays a critical role in the healthy growth and development of young animals. 36187995 8 47 theme HW 1129:1130 arg1 group 1132:1136 the HW group 1125:1136 the HW group 1125:1136 In addition, genera such as Ruminococcus and Anaerotruncus, which were positively correlated with body weight, were enriched in the HW group; those genera, such as Akkermansia and Christensenellaceae, which were negatively correlated with body weight, were enriched in the LW group. 36187995 3 48 theme body 381:384 arg1 HW 400:401 HW 400:401 HW 400:401 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 3 48 theme body 381:384 arg1 group 393:397 the high body weight group 372:397 the high body weight group (HW) 372:402 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 7 49 theme group 898:902 arg1 UCG-005 843:849 UCG-005 843:849 UCG-005 843:849 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 49 theme group 898:902 arg1 Akkermansia 948:958 Akkermansia 948:958 Akkermansia 948:958 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 49 theme group 898:902 arg1 genera 881:886 the core genera 872:886 the core genera of the HW group 872:902 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 49 theme group 898:902 arg1 Bacteroides 909:919 Bacteroides 909:919 Bacteroides 909:919 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 49 theme group 898:902 arg1 Escherichia-Shigella 922:941 Escherichia-Shigella 922:941 Escherichia-Shigella 922:941 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 49 theme group 898:902 arg1 Bacteroides 856:866 Bacteroides 856:866 Bacteroides 856:866 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 49 theme group 898:902 arg1 genera 973:978 the core genera 964:978 the core genera of the LW group 964:994 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 49 theme group 898:902 arg1 Parabacteroides 826:840 Parabacteroides 826:840 Parabacteroides 826:840 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 10 50 theme microbial 1629:1637 arg1 characteristics 1639:1653 the gut microbial characteristics 1621:1653 the gut microbial characteristics of Hainan black goats with different body weights 1621:1703 The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth. 36187995 7 51 theme LW 987:988 arg1 group 990:994 the LW group 983:994 the LW group 983:994 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 3 52 theme weight 386:391 arg1 HW 400:401 HW 400:401 HW 400:401 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 3 52 theme weight 386:391 arg1 group 393:397 the high body weight group 372:397 the high body weight group (HW) 372:402 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 5 53 theme higher 664:669 arg1 diversity 681:689 higher community diversity 664:689 higher community diversity 664:689 The results indicated that the HW group exhibited higher community diversity compared with the LW group, based on the Shannon index. 36187995 4 54 from function 488:495 arg1 feces 504:508 the feces 500:508 the feces of HW and LW groups 500:528 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 10 55 theme gut 1625:1627 arg1 characteristics 1639:1653 the gut microbial characteristics 1621:1653 the gut microbial characteristics of Hainan black goats with different body weights 1621:1703 The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth. 36187995 9 56 theme Glycan 1520:1525 arg1 Biosynthesis 1527:1538 Glycan Biosynthesis 1520:1538 Glycan Biosynthesis 1520:1538 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 1 57 theme Gut 94:96 arg1 microbiota 98:107 Gut microbiota 94:107 Gut microbiota 94:107 Gut microbiota plays a critical role in the healthy growth and development of young animals. 36187995 5 58 theme community 671:679 arg1 diversity 681:689 higher community diversity 664:689 higher community diversity 664:689 The results indicated that the HW group exhibited higher community diversity compared with the LW group, based on the Shannon index. 36187995 6 59 theme groups 779:784 arg1 phyla 756:760 The core phyla 747:760 The core phyla of the HW and LW groups 747:784 The core phyla of the HW and LW groups were both Firmicutes and Bacteroidetes. 36187995 6 59 theme groups 779:784 arg1 Firmicutes 796:805 Firmicutes 796:805 Firmicutes 796:805 The core phyla of the HW and LW groups were both Firmicutes and Bacteroidetes. 36187995 4 60 from composition 461:471 arg1 feces 504:508 the feces 500:508 the feces of HW and LW groups 500:528 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 8 61 theme LW 1270:1271 arg1 group 1273:1277 the LW group 1266:1277 the LW group 1266:1277 In addition, genera such as Ruminococcus and Anaerotruncus, which were positively correlated with body weight, were enriched in the HW group; those genera, such as Akkermansia and Christensenellaceae, which were negatively correlated with body weight, were enriched in the LW group. 36187995 3 62 with lambs 310:314 arg1 date 336:339 the same birth date 321:339 the same birth date 321:339 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 10 63 theme different 1682:1690 arg1 weights 1697:1703 different body weights 1682:1703 different body weights 1682:1703 The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth. 36187995 3 64 theme low 408:410 arg1 weight 417:422 low body weight 408:422 low body weight group (LW) 408:433 In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). 36187995 6 65 theme LW 776:777 arg1 groups 779:784 the HW and LW groups 765:784 the HW and LW groups 765:784 The core phyla of the HW and LW groups were both Firmicutes and Bacteroidetes. 36187995 7 66 theme core 876:879 arg1 UCG-005 843:849 UCG-005 843:849 UCG-005 843:849 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 66 theme core 876:879 arg1 Bacteroides 856:866 Bacteroides 856:866 Bacteroides 856:866 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 66 theme core 876:879 arg1 Parabacteroides 826:840 Parabacteroides 826:840 Parabacteroides 826:840 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 66 theme core 876:879 arg1 genera 881:886 the core genera 872:886 the core genera of the HW group 872:902 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 10 67 theme goats 1671:1675 arg1 characteristics 1639:1653 the gut microbial characteristics 1621:1653 the gut microbial characteristics of Hainan black goats with different body weights 1621:1703 The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth. 36187995 4 68 theme V3-V4 600:604 arg1 region 606:611 the 16S rRNA V3-V4 region 587:611 sequencing the 16S rRNA V3-V4 region 576:611 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 8 69 theme body 1095:1098 arg1 weight 1100:1105 body weight 1095:1105 body weight 1095:1105 In addition, genera such as Ruminococcus and Anaerotruncus, which were positively correlated with body weight, were enriched in the HW group; those genera, such as Akkermansia and Christensenellaceae, which were negatively correlated with body weight, were enriched in the LW group. 36187995 9 70 theme Amino 1334:1338 arg1 Metabolism 1345:1354 Amino Acid Metabolism 1334:1354 Amino Acid Metabolism 1334:1354 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 4 71 dep sequencing 576:585 arg1 region 606:611 the 16S rRNA V3-V4 region 587:611 sequencing the 16S rRNA V3-V4 region 576:611 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 4 72 theme rRNA 595:598 arg1 region 606:611 the 16S rRNA V3-V4 region 587:611 sequencing the 16S rRNA V3-V4 region 576:611 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 0 73 theme Hainan 59:64 arg1 goats 72:76 Hainan black goats 59:76 Hainan black goats 59:76 Association between body weight and distal gut microbes in Hainan black goats at weaning age. 36187995 4 74 theme LW 520:521 arg1 feces 504:508 the feces 500:508 the feces of HW and LW groups 500:528 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 10 75 theme study 1606:1610 arg1 results 1590:1596 The results 1586:1596 The results of this study 1586:1610 The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth. 36187995 9 76 theme KEGG 1309:1312 arg1 pathway 1314:1320 the KEGG pathway 1305:1320 the KEGG pathway 1305:1320 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 36187995 1 77 theme critical 117:124 arg1 role 126:129 a critical role 115:129 a critical role 115:129 Gut microbiota plays a critical role in the healthy growth and development of young animals. 36187995 7 78 theme core 968:971 arg1 Escherichia-Shigella 922:941 Escherichia-Shigella 922:941 Escherichia-Shigella 922:941 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 78 theme core 968:971 arg1 Akkermansia 948:958 Akkermansia 948:958 Akkermansia 948:958 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 78 theme core 968:971 arg1 Bacteroides 909:919 Bacteroides 909:919 Bacteroides 909:919 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 7 78 theme core 968:971 arg1 genera 973:978 the core genera 964:978 the core genera of the LW group 964:994 Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. 36187995 2 79 theme few 206:208 arg1 studies 210:216 few studies 206:216 few studies on the gut microbiota of young Hainan black goats 206:266 However, there are few studies on the gut microbiota of young Hainan black goats. 36187995 4 80 theme fecal 558:562 arg1 samples 564:570 fecal samples 558:570 fecal samples 558:570 The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. 36187995 9 81 theme Nucleotide 1405:1414 arg1 Metabolism 1416:1425 Nucleotide Metabolism 1405:1425 Nucleotide Metabolism 1405:1425 Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. 37206336 6 0 theme summer 877:882 arg1 microbiotas 908:918 The summer, autumn, and spring gut microbiotas 873:918 The summer, autumn, and spring gut microbiotas of both species 873:934 The summer, autumn, and spring gut microbiotas of both species differed, as did the autumn and winter microbiomes. 37206336 7 1 theme gut 1044:1046 arg1 microbiota 1048:1057 the gut microbiota 1040:1057 the gut microbiota of both species 1040:1073 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 2 2 theme more 325:328 arg1 research 330:337 more research 325:337 more research 325:337 The complicated relationships between amphibians and their gut microbiota and how they change throughout the year require more research. 37206336 13 3 theme endangered 1994:2003 arg1 amphibians 2005:2014 endangered amphibians 1994:2014 endangered amphibians 1994:2014 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 13 3 theme endangered 1994:2003 arg1 those 2030:2034 those 2030:2034 those 2030:2034 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 4 4 theme amurensis 566:574 arg1 microbiota 547:556 the gut microbiota 539:556 the gut microbiota of Rana amurensis and Rana dybowskii 539:593 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 10 5 dep biosynthesis 1511:1522 arg1 metabolism 1524:1533 metabolism 1524:1533 metabolism 1524:1533 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 2 6 theme gut 262:264 arg1 microbiota 266:275 their gut microbiota 256:275 their gut microbiota 256:275 The complicated relationships between amphibians and their gut microbiota and how they change throughout the year require more research. 37206336 9 7 theme ± 1272:1272 arg1 abundance 1316:1324 their relative abundance 1301:1324 their relative abundance 1301:1324 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 9 7 theme ± 1272:1272 arg1 % 1278:1278 47.49 ± 3.84% 1266:1278 47.49 ± 3.84% 1266:1278 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 7 8 theme dominant 1022:1029 arg1 phyla 1031:1035 the dominant phyla 1018:1035 the dominant phyla in the gut microbiota of both species 1018:1073 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 7 8 theme dominant 1022:1029 arg1 Proteobacteria 1092:1105 Proteobacteria 1092:1105 Proteobacteria 1092:1105 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 8 9 contain have 1155:1158 arg2 OTUs 1163:1166 10 OTUs 1160:1166 10 OTUs (>90% of all 52 frogs) 1160:1189 All animals have 10 OTUs (>90% of all 52 frogs). 37206336 8 9 contain have 1155:1158 arg1 animals 1147:1153 All animals 1143:1153 All animals 1143:1153 All animals have 10 OTUs (>90% of all 52 frogs). 37206336 10 10 theme microbiota 1408:1417 arg1 functions 1387:1395 the predominant functions 1371:1395 the predominant functions of the gut microbiota in these two Rana 1371:1435 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 10 11 theme membrane 1536:1543 arg1 transport 1545:1553 membrane transport 1536:1553 membrane transport 1536:1553 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 10 11 theme membrane 1536:1543 arg1 metabolism 1466:1475 carbohydrate metabolism 1453:1475 carbohydrate metabolism 1453:1475 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 6 12 theme gut 904:906 arg1 microbiotas 908:918 The summer, autumn, and spring gut microbiotas 873:918 The summer, autumn, and spring gut microbiotas of both species 873:934 The summer, autumn, and spring gut microbiotas of both species differed, as did the autumn and winter microbiomes. 37206336 7 13 from Bacteroidetes 1108:1120 arg1 winter 1010:1015 winter 1010:1015 winter 1010:1015 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 7 13 from Bacteroidetes 1108:1120 arg1 autumn 999:1004 autumn 999:1004 autumn 999:1004 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 7 13 from Bacteroidetes 1108:1120 arg1 summer 991:996 summer 991:996 summer 991:996 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 0 14 theme hibernation 103:113 arg1 end 96:98 end 96:98 end 96:98 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 14 theme hibernation 103:113 arg1 beginning 82:90 beginning 82:90 beginning 82:90 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 8 15 theme frogs 1184:1188 arg1 % 1172:1172 >90% 1169:1172 >90% of all 52 frogs 1169:1188 All animals have 10 OTUs (>90% of all 52 frogs). 37206336 8 15 theme frogs 1184:1188 arg1 frogs 1184:1188 all 52 frogs 1177:1188 all 52 frogs 1177:1188 All animals have 10 OTUs (>90% of all 52 frogs). 37206336 9 16 theme relative 1307:1314 arg1 abundance 1316:1324 their relative abundance 1301:1324 their relative abundance 1301:1324 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 6 17 theme autumn 885:890 arg1 microbiotas 908:918 The summer, autumn, and spring gut microbiotas 873:918 The summer, autumn, and spring gut microbiotas of both species 873:934 The summer, autumn, and spring gut microbiotas of both species differed, as did the autumn and winter microbiomes. 37206336 0 18 from beginning 82:90 arg1 Characteristics 0:14 Characteristics 0:14 Characteristics 0:14 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 18 from beginning 82:90 arg1 comparison 22:31 a comparison 20:31 a comparison of the gut microbiota in two frog species at the beginning and end of hibernation 20:113 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 18 from beginning 82:90 arg1 microbiota 44:53 the gut microbiota 36:53 the gut microbiota in two frog species at the beginning and end of hibernation 36:113 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 6 19 theme autumn 957:962 arg1 microbiomes 975:985 the autumn and winter microbiomes 953:985 microbiomes 975:985 The summer, autumn, and spring gut microbiotas of both species differed, as did the autumn and winter microbiomes. 37206336 5 20 theme frog 727:730 arg1 species 732:738 Both frog species 722:738 Both frog species 722:738 Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. 37206336 13 21 theme amphibians 1904:1913 arg1 microbiota 1890:1899 the gut microbiota 1882:1899 the gut microbiota of amphibians 1882:1913 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 2 22 theme complicated 207:217 arg1 relationships 219:231 The complicated relationships 203:231 The complicated relationships between amphibians and their gut microbiota and how they change throughout the year 203:315 The complicated relationships between amphibians and their gut microbiota and how they change throughout the year require more research. 37206336 0 23 theme frog 62:65 arg1 species 67:73 two frog species 58:73 two frog species 58:73 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 24 from Characteristics 0:14 arg1 end 96:98 end 96:98 end 96:98 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 24 from Characteristics 0:14 arg1 species 67:73 two frog species 58:73 two frog species 58:73 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 24 from Characteristics 0:14 arg1 beginning 82:90 beginning 82:90 beginning 82:90 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 13 25 theme physiological 2136:2148 arg1 states 2150:2155 various physiological states 2128:2155 various physiological states 2128:2155 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 0 26 dep beginning 82:90 arg1 the 78:80 the 78:80 the 78:80 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 6 27 theme species 928:934 arg1 microbiotas 908:918 The summer, autumn, and spring gut microbiotas 873:918 The summer, autumn, and spring gut microbiotas of both species 873:934 The summer, autumn, and spring gut microbiotas of both species differed, as did the autumn and winter microbiomes. 37206336 6 28 dep did 949:951 arg1 as 946:947 as 946:947 as 946:947 The summer, autumn, and spring gut microbiotas of both species differed, as did the autumn and winter microbiomes. 37206336 10 29 theme Global 1478:1483 arg1 maps 1498:1501 Global and overview maps 1478:1501 maps 1498:1501 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 10 29 theme Global 1478:1483 arg1 metabolism 1466:1475 carbohydrate metabolism 1453:1475 carbohydrate metabolism 1453:1475 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 5 30 from diversity 772:780 arg1 winter 808:813 winter 808:813 winter 808:813 Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. 37206336 5 30 from diversity 772:780 arg1 summer 785:790 summer 785:790 summer than autumn 785:802 Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. 37206336 3 31 theme hypothermic 365:375 arg1 fasting 377:383 Short-term and long-term hypothermic fasting 340:383 Short-term and long-term hypothermic fasting of amphibians 340:397 Short-term and long-term hypothermic fasting of amphibians may affect gut microbiota differently; however, these changes have not been explored. 37206336 7 32 from Proteobacteria 1092:1105 arg1 winter 1010:1015 winter 1010:1015 winter 1010:1015 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 7 32 from Proteobacteria 1092:1105 arg1 autumn 999:1004 autumn 999:1004 autumn 999:1004 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 7 32 from Proteobacteria 1092:1105 arg1 summer 991:996 summer 991:996 summer 991:996 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 4 33 theme Illumina 701:708 arg1 sequencing 710:719 high-throughput Illumina sequencing 685:719 high-throughput Illumina sequencing 685:719 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 3 34 theme gut 410:412 arg1 microbiota 414:423 gut microbiota 410:423 gut microbiota 410:423 Short-term and long-term hypothermic fasting of amphibians may affect gut microbiota differently; however, these changes have not been explored. 37206336 8 35 dep OTUs 1163:1166 arg1 % 1172:1172 >90% 1169:1172 >90% of all 52 frogs 1169:1188 All animals have 10 OTUs (>90% of all 52 frogs). 37206336 8 35 dep OTUs 1163:1166 arg1 frogs 1184:1188 all 52 frogs 1177:1188 all 52 frogs 1177:1188 All animals have 10 OTUs (>90% of all 52 frogs). 37206336 9 36 contain had 1205:1207 arg1 species 1197:1203 Both species 1192:1203 Both species 1192:1203 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 9 36 contain had 1205:1207 arg2 OTUs 1212:1215 23 OTUs 1209:1215 23 OTUs (>90% of all 28 frogs) 1209:1238 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 10 37 theme overview 1489:1496 arg1 maps 1498:1501 Global and overview maps 1478:1501 maps 1498:1501 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 10 37 theme overview 1489:1496 arg1 metabolism 1466:1475 carbohydrate metabolism 1453:1475 carbohydrate metabolism 1453:1475 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 7 38 theme species 1067:1073 arg1 microbiota 1048:1057 the gut microbiota 1040:1057 the gut microbiota of both species 1040:1073 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 5 39 theme gut 751:753 arg1 diversity 772:780 higher gut microbiota alpha diversity 744:780 higher gut microbiota alpha diversity in summer than autumn and winter 744:813 Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. 37206336 6 40 theme winter 968:973 arg1 microbiomes 975:985 the autumn and winter microbiomes 953:985 microbiomes 975:985 The summer, autumn, and spring gut microbiotas of both species differed, as did the autumn and winter microbiomes. 37206336 0 41 theme gut 40:42 arg1 microbiota 44:53 the gut microbiota 36:53 the gut microbiota in two frog species at the beginning and end of hibernation 36:113 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 42 from comparison 22:31 arg1 end 96:98 end 96:98 end 96:98 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 42 from comparison 22:31 arg1 species 67:73 two frog species 58:73 two frog species 58:73 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 42 from comparison 22:31 arg1 beginning 82:90 beginning 82:90 beginning 82:90 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 11 43 theme R. 1658:1659 arg1 group 1671:1675 the R. amurensis group 1654:1675 the R. amurensis group 1654:1675 The BugBase analysis estimated that among the seasons in the R. amurensis group, Facultatively_Anaerobic, Forms_Biofilms, Gram_Negative, Gram_Positive, Potentially_Pathogenic were significantly different. 37206336 10 44 theme predominant 1375:1385 arg1 functions 1387:1395 the predominant functions 1371:1395 the predominant functions of the gut microbiota in these two Rana 1371:1435 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 5 45 theme microbiota 755:764 arg1 diversity 772:780 higher gut microbiota alpha diversity 744:780 higher gut microbiota alpha diversity in summer than autumn and winter 744:813 Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. 37206336 4 46 theme dybowskii 585:593 arg1 microbiota 547:556 the gut microbiota 539:556 the gut microbiota of Rana amurensis and Rana dybowskii 539:593 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 11 47 from seasons 1643:1649 arg1 group 1671:1675 the R. amurensis group 1654:1675 the R. amurensis group 1654:1675 The BugBase analysis estimated that among the seasons in the R. amurensis group, Facultatively_Anaerobic, Forms_Biofilms, Gram_Negative, Gram_Positive, Potentially_Pathogenic were significantly different. 37206336 4 48 theme microbiota 547:556 arg1 composition 504:514 composition 504:514 composition 504:514 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 4 48 theme microbiota 547:556 arg1 characteristics 520:534 characteristics 520:534 characteristics 520:534 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 10 49 theme gut 1404:1406 arg1 microbiota 1408:1417 the gut microbiota 1400:1417 the gut microbiota 1400:1417 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 9 50 theme 47.49 1266:1270 arg1 abundance 1316:1324 their relative abundance 1301:1324 their relative abundance 1301:1324 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 9 50 theme 47.49 1266:1270 arg1 % 1278:1278 47.49 ± 3.84% 1266:1278 47.49 ± 3.84% 1266:1278 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 12 51 theme R. 1839:1840 arg1 dybowskii 1842:1850 R. dybowskii 1839:1850 R. dybowskii 1839:1850 However, there was no difference for R. dybowskii. 37206336 5 52 theme alpha 766:770 arg1 diversity 772:780 higher gut microbiota alpha diversity 744:780 higher gut microbiota alpha diversity in summer than autumn and winter 744:813 Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. 37206336 4 53 theme short-term 618:627 arg1 autumn 610:615 autumn 610:615 autumn (short-term fasting) 610:636 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 4 53 theme short-term 618:627 arg1 fasting 629:635 short-term fasting 618:635 short-term fasting 618:635 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 5 54 theme significant 823:833 arg1 variations 835:844 no significant variations 820:844 no significant variations between autumn and spring 820:870 Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. 37206336 9 55 theme ± 1290:1290 arg1 abundance 1316:1324 their relative abundance 1301:1324 their relative abundance 1301:1324 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 9 55 theme ± 1290:1290 arg1 % 1296:1296 63.17 ± 3.69% 1284:1296 63.17 ± 3.69% of their relative abundance 1284:1324 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 0 56 from species 67:73 arg1 Characteristics 0:14 Characteristics 0:14 Characteristics 0:14 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 56 from species 67:73 arg1 comparison 22:31 a comparison 20:31 a comparison of the gut microbiota in two frog species at the beginning and end of hibernation 20:113 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 1 57 theme gut 176:178 arg1 microbiota 180:189 the gut microbiota 172:189 the gut microbiota of animals 172:200 Season has been suggested to contribute to variation in the gut microbiota of animals. 37206336 6 58 theme spring 897:902 arg1 microbiotas 908:918 The summer, autumn, and spring gut microbiotas 873:918 The summer, autumn, and spring gut microbiotas of both species 873:934 The summer, autumn, and spring gut microbiotas of both species differed, as did the autumn and winter microbiomes. 37206336 9 59 theme frogs 1233:1237 arg1 % 1221:1221 >90% 1218:1221 >90% of all 28 frogs 1218:1237 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 9 59 theme frogs 1233:1237 arg1 frogs 1233:1237 all 28 frogs 1226:1237 all 28 frogs 1226:1237 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 13 60 theme various 2128:2134 arg1 states 2150:2155 various physiological states 2128:2155 various physiological states 2128:2155 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 7 61 from Actinobacteria 1127:1140 arg1 winter 1010:1015 winter 1010:1015 winter 1010:1015 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 7 61 from Actinobacteria 1127:1140 arg1 autumn 999:1004 autumn 999:1004 autumn 999:1004 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 7 61 from Actinobacteria 1127:1140 arg1 summer 991:996 summer 991:996 summer 991:996 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 9 62 theme abundance 1316:1324 arg1 abundance 1316:1324 their relative abundance 1301:1324 their relative abundance 1301:1324 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 9 62 theme abundance 1316:1324 arg1 % 1296:1296 63.17 ± 3.69% 1284:1296 63.17 ± 3.69% of their relative abundance 1284:1324 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 9 62 theme abundance 1316:1324 arg1 % 1278:1278 47.49 ± 3.84% 1266:1278 47.49 ± 3.84% 1266:1278 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 13 63 theme environmental 2161:2173 arg1 conditions 2175:2184 environmental conditions 2161:2184 environmental conditions 2161:2184 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 5 64 contain had 740:742 arg1 species 732:738 Both frog species 722:738 Both frog species 722:738 Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. 37206336 5 64 contain had 740:742 arg2 diversity 772:780 higher gut microbiota alpha diversity 744:780 higher gut microbiota alpha diversity in summer than autumn and winter 744:813 Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. 37206336 4 65 dep composition 504:514 arg1 the 500:502 the 500:502 the 500:502 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 13 66 theme microbiota 2111:2120 arg1 role 2103:2106 the role 2099:2106 the role of microbiota 2099:2120 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 9 67 dep OTUs 1212:1215 arg1 % 1221:1221 >90% 1218:1221 >90% of all 28 frogs 1218:1237 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 9 67 dep OTUs 1212:1215 arg1 frogs 1233:1237 all 28 frogs 1226:1237 all 28 frogs 1226:1237 Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. 37206336 4 68 theme long-term 650:658 arg1 winter 642:647 winter 642:647 winter (long-term fasting) 642:667 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 4 68 theme long-term 650:658 arg1 fasting 660:666 long-term fasting 650:666 long-term fasting 650:666 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 11 69 theme BugBase 1601:1607 arg1 analysis 1609:1616 The BugBase analysis 1597:1616 The BugBase analysis 1597:1616 The BugBase analysis estimated that among the seasons in the R. amurensis group, Facultatively_Anaerobic, Forms_Biofilms, Gram_Negative, Gram_Positive, Potentially_Pathogenic were significantly different. 37206336 13 70 theme environmental 1925:1937 arg1 changes 1939:1945 environmental changes 1925:1945 environmental changes 1925:1945 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 3 71 theme Short-term 340:349 arg1 fasting 377:383 Short-term and long-term hypothermic fasting 340:383 Short-term and long-term hypothermic fasting of amphibians 340:397 Short-term and long-term hypothermic fasting of amphibians may affect gut microbiota differently; however, these changes have not been explored. 37206336 0 72 from microbiota 44:53 arg1 species 67:73 two frog species 58:73 two frog species 58:73 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 7 73 dep Proteobacteria 1092:1105 arg1 Firmicutes 1080:1089 Firmicutes 1080:1089 Firmicutes 1080:1089 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 10 74 theme Glycan 1504:1509 arg1 biosynthesis 1511:1522 Glycan biosynthesis metabolism, membrane transport, and replication and repair 1504:1581 biosynthesis 1511:1522 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 10 74 theme Glycan 1504:1509 arg1 metabolism 1466:1475 carbohydrate metabolism 1453:1475 carbohydrate metabolism 1453:1475 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 13 75 theme gut 1886:1888 arg1 microbiota 1890:1899 the gut microbiota 1882:1899 the gut microbiota of amphibians 1882:1913 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 4 76 theme high-throughput 685:699 arg1 sequencing 710:719 high-throughput Illumina sequencing 685:719 high-throughput Illumina sequencing 685:719 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 10 77 theme carbohydrate 1453:1464 arg1 transport 1545:1553 membrane transport 1536:1553 membrane transport 1536:1553 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 10 77 theme carbohydrate 1453:1464 arg1 metabolism 1466:1475 carbohydrate metabolism 1453:1475 carbohydrate metabolism 1453:1475 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 10 77 theme carbohydrate 1453:1464 arg1 translation 1584:1594 translation 1584:1594 translation 1584:1594 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 10 77 theme carbohydrate 1453:1464 arg1 biosynthesis 1511:1522 Glycan biosynthesis metabolism, membrane transport, and replication and repair 1504:1581 biosynthesis 1511:1522 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 10 77 theme carbohydrate 1453:1464 arg1 replication 1560:1570 replication 1560:1570 replication 1560:1570 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 10 77 theme carbohydrate 1453:1464 arg1 maps 1498:1501 Global and overview maps 1478:1501 maps 1498:1501 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 3 78 theme long-term 355:363 arg1 fasting 377:383 Short-term and long-term hypothermic fasting 340:383 Short-term and long-term hypothermic fasting of amphibians 340:397 Short-term and long-term hypothermic fasting of amphibians may affect gut microbiota differently; however, these changes have not been explored. 37206336 4 79 theme gut 543:545 arg1 microbiota 547:556 the gut microbiota 539:556 the gut microbiota of Rana amurensis and Rana dybowskii 539:593 In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. 37206336 5 80 theme higher 744:749 arg1 diversity 772:780 higher gut microbiota alpha diversity 744:780 higher gut microbiota alpha diversity in summer than autumn and winter 744:813 Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. 37206336 7 81 from phyla 1031:1035 arg1 microbiota 1048:1057 the gut microbiota 1040:1057 the gut microbiota of both species 1040:1073 In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. 37206336 0 82 theme microbiota 44:53 arg1 Characteristics 0:14 Characteristics 0:14 Characteristics 0:14 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 82 theme microbiota 44:53 arg1 comparison 22:31 a comparison 20:31 a comparison of the gut microbiota in two frog species at the beginning and end of hibernation 20:113 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 3 83 theme amphibians 388:397 arg1 fasting 377:383 Short-term and long-term hypothermic fasting 340:383 Short-term and long-term hypothermic fasting of amphibians 340:397 Short-term and long-term hypothermic fasting of amphibians may affect gut microbiota differently; however, these changes have not been explored. 37206336 10 84 theme PICRUSt2 1341:1348 arg1 analysis 1350:1357 PICRUSt2 analysis 1341:1357 PICRUSt2 analysis 1341:1357 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 13 85 theme microbiota 2064:2073 arg1 research 2075:2082 microbiota research 2064:2082 microbiota research 2064:2082 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 10 86 from functions 1387:1395 arg1 Rana 1432:1435 these two Rana 1422:1435 these two Rana 1422:1435 PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. 37206336 11 87 theme amurensis 1661:1669 arg1 group 1671:1675 the R. amurensis group 1654:1675 the R. amurensis group 1654:1675 The BugBase analysis estimated that among the seasons in the R. amurensis group, Facultatively_Anaerobic, Forms_Biofilms, Gram_Negative, Gram_Positive, Potentially_Pathogenic were significantly different. 37206336 1 88 theme animals 194:200 arg1 microbiota 180:189 the gut microbiota 172:189 the gut microbiota of animals 172:200 Season has been suggested to contribute to variation in the gut microbiota of animals. 37206336 13 89 theme amphibians 2005:2014 arg1 conservation 1978:1989 the conservation 1974:1989 the conservation of endangered amphibians, particularly those that hibernate 1974:2049 The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions. 37206336 0 90 from end 96:98 arg1 Characteristics 0:14 Characteristics 0:14 Characteristics 0:14 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 90 from end 96:98 arg1 comparison 22:31 a comparison 20:31 a comparison of the gut microbiota in two frog species at the beginning and end of hibernation 20:113 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 37206336 0 90 from end 96:98 arg1 microbiota 44:53 the gut microbiota 36:53 the gut microbiota in two frog species at the beginning and end of hibernation 36:113 Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation. 35676564 4 0 theme gene 536:539 arg1 ALG3 541:544 N-linked glycosylation gene ALG3 513:544 N-linked glycosylation gene ALG3 513:544 Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. 35676564 7 1 theme immune 1286:1291 arg1 responses 1293:1301 anti-tumor immune responses 1275:1301 anti-tumor immune responses 1275:1301 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 9 2 theme ALG3 1481:1484 arg1 role 1473:1476 an unappreciated role 1456:1476 an unappreciated role of ALG3 in regulating tumor immunogenicity 1456:1519 Taken together, we reveal an unappreciated role of ALG3 in regulating tumor immunogenicity and propose a potential therapeutic strategy for enhancing cancer immunotherapy. 35676564 1 3 theme certain 172:178 arg1 cancers 195:201 certain advanced-stage cancers 172:201 certain advanced-stage cancers 172:201 Immune checkpoint blockade therapy has drastically improved the prognosis of certain advanced-stage cancers. 35676564 9 4 theme unappreciated 1459:1471 arg1 role 1473:1476 an unappreciated role 1456:1476 an unappreciated role of ALG3 in regulating tumor immunogenicity 1456:1519 Taken together, we reveal an unappreciated role of ALG3 in regulating tumor immunogenicity and propose a potential therapeutic strategy for enhancing cancer immunotherapy. 35676564 9 5 theme cancer 1580:1585 arg1 immunotherapy 1587:1599 cancer immunotherapy 1580:1599 cancer immunotherapy 1580:1599 Taken together, we reveal an unappreciated role of ALG3 in regulating tumor immunogenicity and propose a potential therapeutic strategy for enhancing cancer immunotherapy. 35676564 5 6 theme cancer 825:830 arg1 models 815:820 mouse models 809:820 mouse models of cancer 809:830 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 4 7 theme mouse 549:553 arg1 cells 562:566 mouse cancer cells 549:566 mouse cancer cells 549:566 Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. 35676564 7 8 theme pro-inflammatory 1226:1241 arg1 microenvironment 1243:1258 a pro-inflammatory microenvironment 1224:1258 a pro-inflammatory microenvironment 1224:1258 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 8 9 with subjects 1313:1320 arg1 cancer 1327:1332 cancer 1327:1332 cancer 1327:1332 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 1 10 theme advanced-stage 180:193 arg1 cancers 195:201 certain advanced-stage cancers 172:201 certain advanced-stage cancers 172:201 Immune checkpoint blockade therapy has drastically improved the prognosis of certain advanced-stage cancers. 35676564 6 11 theme glycosylation 932:944 arg1 modification 946:957 post-translational N-linked glycosylation modification 904:957 post-translational N-linked glycosylation modification 904:957 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 5 12 from growth 799:804 arg1 models 815:820 mouse models 809:820 mouse models of cancer 809:830 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 8 13 from levels 1344:1349 arg1 tissues 1379:1385 tumor tissues 1373:1385 tumor tissues 1373:1385 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 5 14 theme N-linked 690:697 arg1 glycosylation 699:711 N-linked glycosylation 690:711 N-linked glycosylation 690:711 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 6 15 theme inhibiting 864:873 arg1 ALG3 875:878 inhibiting ALG3 864:878 inhibiting ALG3 864:878 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 3 16 theme endoplasmic 404:414 arg1 ER 427:428 ER 427:428 ER 427:428 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 3 16 theme endoplasmic 404:414 arg1 reticulum 416:424 the endoplasmic reticulum 400:424 the endoplasmic reticulum (ER) 400:429 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 6 17 theme lipid 980:984 arg1 accumulation 986:997 excessive lipid accumulation 970:997 excessive lipid accumulation 970:997 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 7 18 theme anti-tumor 1275:1284 arg1 responses 1293:1301 anti-tumor immune responses 1275:1301 anti-tumor immune responses 1275:1301 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 9 19 theme tumor 1500:1504 arg1 immunogenicity 1506:1519 tumor immunogenicity 1500:1519 tumor immunogenicity 1500:1519 Taken together, we reveal an unappreciated role of ALG3 in regulating tumor immunogenicity and propose a potential therapeutic strategy for enhancing cancer immunotherapy. 35676564 8 20 theme elevated 1335:1342 arg1 levels 1344:1349 elevated levels 1335:1349 elevated levels of ALG3 expression in tumor tissues 1335:1385 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 6 21 theme excessive 970:978 arg1 accumulation 986:997 excessive lipid accumulation 970:997 excessive lipid accumulation 970:997 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 8 22 theme ALG3 1354:1357 arg1 expression 1359:1368 ALG3 expression 1354:1368 ALG3 expression in tumor tissues 1354:1385 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 1 23 theme cancers 195:201 arg1 prognosis 159:167 the prognosis 155:167 the prognosis of certain advanced-stage cancers 155:201 Immune checkpoint blockade therapy has drastically improved the prognosis of certain advanced-stage cancers. 35676564 9 24 dep potential 1535:1543 arg1 therapeutic 1545:1555 therapeutic 1545:1555 therapeutic 1545:1555 Taken together, we reveal an unappreciated role of ALG3 in regulating tumor immunogenicity and propose a potential therapeutic strategy for enhancing cancer immunotherapy. 35676564 4 25 theme glycosylation 522:534 arg1 ALG3 541:544 N-linked glycosylation gene ALG3 513:544 N-linked glycosylation gene ALG3 513:544 Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. 35676564 8 26 theme tumor 1373:1377 arg1 tissues 1379:1385 tumor tissues 1373:1385 tumor tissues 1373:1385 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 6 27 theme N-linked 923:930 arg1 modification 946:957 post-translational N-linked glycosylation modification 904:957 post-translational N-linked glycosylation modification 904:957 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 7 28 theme glycosylation 1105:1117 arg1 hyperperoxidation 1145:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation 1096:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation 1096:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 8 29 from expression 1359:1368 arg1 tissues 1379:1385 tumor tissues 1373:1385 tumor tissues 1373:1385 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 4 30 theme N-linked 513:520 arg1 ALG3 541:544 N-linked glycosylation gene ALG3 513:544 N-linked glycosylation gene ALG3 513:544 Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. 35676564 3 31 dep boost 436:440 arg1 inhibiting 317:326 inhibiting 317:326 inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER) 317:429 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 5 32 theme mouse 809:813 arg1 models 815:820 mouse models 809:820 mouse models of cancer 809:830 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 1 33 theme Immune 95:100 arg1 therapy 122:128 Immune checkpoint blockade therapy 95:128 Immune checkpoint blockade therapy 95:128 Immune checkpoint blockade therapy has drastically improved the prognosis of certain advanced-stage cancers. 35676564 7 34 theme cancer 1198:1203 arg1 cells 1205:1209 cancer cells 1198:1209 cancer cells 1198:1209 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 8 35 theme patient 1412:1418 arg1 survival 1420:1427 poor patient survival 1407:1427 poor patient survival 1407:1427 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 6 36 theme cancer 1082:1087 arg1 cells 1089:1093 cancer cells 1082:1093 cancer cells 1082:1093 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 5 37 theme ALG3 671:674 arg1 inhibition 676:685 ALG3 inhibition 671:685 ALG3 inhibition 671:685 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 1 38 theme checkpoint 102:111 arg1 therapy 122:128 Immune checkpoint blockade therapy 95:128 Immune checkpoint blockade therapy 95:128 Immune checkpoint blockade therapy has drastically improved the prognosis of certain advanced-stage cancers. 35676564 8 39 theme poor 1407:1410 arg1 survival 1420:1427 poor patient survival 1407:1427 poor patient survival 1407:1427 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 4 40 from growth 599:604 arg1 mice 609:612 mice 609:612 mice 609:612 Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. 35676564 6 41 from lipogenesis 1067:1077 arg1 cells 1089:1093 cancer cells 1082:1093 cancer cells 1082:1093 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 8 42 theme expression 1359:1368 arg1 levels 1344:1349 elevated levels 1335:1349 elevated levels of ALG3 expression in tumor tissues 1335:1385 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 1 43 theme blockade 113:120 arg1 therapy 122:128 Immune checkpoint blockade therapy 95:128 Immune checkpoint blockade therapy 95:128 Immune checkpoint blockade therapy has drastically improved the prognosis of certain advanced-stage cancers. 35676564 9 44 theme potential 1535:1543 arg1 strategy 1557:1564 a potential therapeutic strategy 1533:1564 a potential therapeutic strategy for enhancing cancer immunotherapy 1533:1599 Taken together, we reveal an unappreciated role of ALG3 in regulating tumor immunogenicity and propose a potential therapeutic strategy for enhancing cancer immunotherapy. 35676564 3 45 theme blockade 486:493 arg1 therapy 495:501 immune checkpoint blockade therapy 468:501 immune checkpoint blockade therapy 468:501 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 0 46 theme ALG3 14:17 arg1 Inhibition 0:9 Inhibition 0:9 Inhibition of ALG3 0:17 Inhibition of ALG3 stimulates cancer cell immunogenic ferroptosis to potentiate immunotherapy. 35676564 7 47 link N-linked 1096:1103 arg1 hyperperoxidation 1145:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation 1096:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation 1096:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 5 48 theme anti-PD1 761:768 arg1 therapy 770:776 anti-PD1 therapy 761:776 anti-PD1 therapy 761:776 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 3 49 from glycosylation 383:395 arg1 ER 427:428 ER 427:428 ER 427:428 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 3 49 from glycosylation 383:395 arg1 reticulum 416:424 the endoplasmic reticulum 400:424 the endoplasmic reticulum (ER) 400:429 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 6 50 theme sterol-regulated 1007:1022 arg1 lipogenesis 1067:1077 sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis 1007:1077 sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells 1007:1093 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 0 51 theme cell 37:40 arg1 ferroptosis 54:64 cancer cell immunogenic ferroptosis 30:64 cancer cell immunogenic ferroptosis 30:64 Inhibition of ALG3 stimulates cancer cell immunogenic ferroptosis to potentiate immunotherapy. 35676564 6 52 theme -dependent 1056:1065 arg1 lipogenesis 1067:1077 sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis 1007:1077 sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells 1007:1093 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 7 53 theme cells 1205:1209 arg1 ferroptosis 1183:1193 immunogenic ferroptosis 1171:1193 immunogenic ferroptosis of cancer cells 1171:1209 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 6 54 theme modification 946:957 arg1 deficiencies 888:899 deficiencies 888:899 deficiencies of post-translational N-linked glycosylation modification 888:957 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 3 55 theme immune 468:473 arg1 therapy 495:501 immune checkpoint blockade therapy 468:501 immune checkpoint blockade therapy 468:501 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 0 56 theme cancer 30:35 arg1 ferroptosis 54:64 cancer cell immunogenic ferroptosis 30:64 cancer cell immunogenic ferroptosis 30:64 Inhibition of ALG3 stimulates cancer cell immunogenic ferroptosis to potentiate immunotherapy. 35676564 3 57 gly glycosylation 383:395 arg1 ER 427:428 ER 427:428 ER 427:428 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 3 57 gly glycosylation 383:395 arg1 reticulum 416:424 the endoplasmic reticulum 400:424 the endoplasmic reticulum (ER) 400:429 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 5 58 theme tumor 793:797 arg1 growth 799:804 tumor growth 793:804 tumor growth in mouse models of cancer 793:830 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 5 59 dep inhibition 676:685 arg1 treatment 735:743 inhibitor tunicamycin treatment 713:743 inhibitor tunicamycin treatment 713:743 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 3 60 theme checkpoint 475:484 arg1 therapy 495:501 immune checkpoint blockade therapy 468:501 immune checkpoint blockade therapy 468:501 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 4 61 link N-linked 513:520 arg1 ALG3 541:544 N-linked glycosylation gene ALG3 513:544 N-linked glycosylation gene ALG3 513:544 Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. 35676564 5 62 theme inhibitor 713:721 arg1 treatment 735:743 inhibitor tunicamycin treatment 713:743 inhibitor tunicamycin treatment 713:743 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 3 63 theme tumors 458:463 arg1 response 446:453 the response 442:453 the response of tumors to immune checkpoint blockade therapy 442:501 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 2 64 theme adverse 251:257 arg1 events 259:264 immune-related adverse events 236:264 immune-related adverse events 236:264 However, low response rates and immune-related adverse events remain important limitations. 35676564 0 65 theme immunogenic 42:52 arg1 ferroptosis 54:64 cancer cell immunogenic ferroptosis 30:64 cancer cell immunogenic ferroptosis 30:64 Inhibition of ALG3 stimulates cancer cell immunogenic ferroptosis to potentiate immunotherapy. 35676564 5 66 theme tunicamycin 723:733 arg1 treatment 735:743 inhibitor tunicamycin treatment 713:743 inhibitor tunicamycin treatment 713:743 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 6 67 theme post-translational 904:921 arg1 modification 946:957 post-translational N-linked glycosylation modification 904:957 post-translational N-linked glycosylation modification 904:957 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 2 68 theme immune-related 236:249 arg1 events 259:264 immune-related adverse events 236:264 immune-related adverse events 236:264 However, low response rates and immune-related adverse events remain important limitations. 35676564 7 69 theme deficiency-mediated 1119:1137 arg1 hyperperoxidation 1145:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation 1096:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation 1096:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 6 70 link N-linked 923:930 arg1 modification 946:957 post-translational N-linked glycosylation modification 904:957 post-translational N-linked glycosylation modification 904:957 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 8 71 theme human 1307:1311 arg1 subjects 1313:1320 human subjects 1307:1320 human subjects with cancer 1307:1332 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 8 72 from tissues 1379:1385 arg1 levels 1344:1349 elevated levels 1335:1349 elevated levels of ALG3 expression in tumor tissues 1335:1385 In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. 35676564 7 73 theme immunogenic 1171:1181 arg1 ferroptosis 1183:1193 immunogenic ferroptosis 1171:1193 immunogenic ferroptosis of cancer cells 1171:1209 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 7 74 theme lipid 1139:1143 arg1 hyperperoxidation 1145:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation 1096:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation 1096:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 4 75 theme cytotoxic 639:647 arg1 cells 651:655 cytotoxic T cells 639:655 cytotoxic T cells 639:655 Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. 35676564 2 76 theme response 217:224 arg1 rates 226:230 low response rates 213:230 low response rates 213:230 However, low response rates and immune-related adverse events remain important limitations. 35676564 7 77 theme N-linked 1096:1103 arg1 hyperperoxidation 1145:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation 1096:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation 1096:1161 N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. 35676564 4 78 theme cancer 555:560 arg1 cells 562:566 mouse cancer cells 549:566 mouse cancer cells 549:566 Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. 35676564 2 79 theme low 213:215 arg1 rates 226:230 low response rates 213:230 low response rates 213:230 However, low response rates and immune-related adverse events remain important limitations. 35676564 5 80 link N-linked 690:697 arg1 glycosylation 699:711 N-linked glycosylation 690:711 N-linked glycosylation 690:711 Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. 35676564 3 81 theme protein 375:381 arg1 glycosylation 383:395 protein glycosylation 375:395 protein glycosylation in the endoplasmic reticulum (ER) 375:429 Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. 35676564 6 82 theme element-binding 1024:1038 arg1 lipogenesis 1067:1077 sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis 1007:1077 sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells 1007:1093 Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. 35676564 2 83 theme important 273:281 arg1 limitations 283:293 important limitations 273:293 important limitations 273:293 However, low response rates and immune-related adverse events remain important limitations. 35676564 4 84 theme T 649:649 arg1 cells 651:655 cytotoxic T cells 639:655 cytotoxic T cells 639:655 Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. 35663757 0 0 theme porang 100:105 arg1 Blume 144:148 Blume 144:148 Blume 144:148 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 0 0 theme porang 100:105 arg1 glucomannan 107:117 octenyl succinic anhydride-modified porang glucomannan 64:117 octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume) 64:149 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 8 1 theme such 1160:1163 arg1 characteristics 1102:1116 The characteristics 1098:1116 The characteristics of OSA-modified porang glucomannan (PGOS) such as 1098:1166 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 1 theme such 1160:1163 arg1 Degree 1202:1207 Degree 1202:1207 Degree of Substitution (DS), contact angle, and viscosity 1202:1258 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 1 theme such 1160:1163 arg1 stability 1191:1199 stability 1191:1199 stability 1191:1199 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 1 theme such 1160:1163 arg1 capacity 1178:1185 emulsion capacity 1169:1185 emulsion capacity 1169:1185 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 9 2 theme OSA 1366:1368 arg1 substitution 1370:1381 OSA substitution 1366:1381 OSA substitution 1366:1381 FT-IR analysis confirmed the presence of OSA substitution at 1734 cm-1. 35663757 0 3 theme anhydride-modified 81:98 arg1 Blume 144:148 Blume 144:148 Blume 144:148 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 0 3 theme anhydride-modified 81:98 arg1 glucomannan 107:117 octenyl succinic anhydride-modified porang glucomannan 64:117 octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume) 64:149 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 7 4 theme increased 1030:1038 arg1 viscosity 1040:1048 increased viscosity 1030:1048 increased viscosity 1030:1048 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity confirmed that OSA substitution occurred in PG. 35663757 8 5 theme glucomannan 1141:1151 arg1 characteristics 1102:1116 The characteristics 1098:1116 The characteristics of OSA-modified porang glucomannan (PGOS) such as 1098:1166 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 5 theme glucomannan 1141:1151 arg1 Degree 1202:1207 Degree 1202:1207 Degree of Substitution (DS), contact angle, and viscosity 1202:1258 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 5 theme glucomannan 1141:1151 arg1 stability 1191:1199 stability 1191:1199 stability 1191:1199 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 5 theme glucomannan 1141:1151 arg1 capacity 1178:1185 emulsion capacity 1169:1185 emulsion capacity 1169:1185 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 6 6 theme optimum 795:801 arg1 conditions 803:812 The optimum conditions 791:812 The optimum conditions that resulted in the highest emulsion capacity and stability 791:873 The optimum conditions that resulted in the highest emulsion capacity and stability were obtained at concentrations of Na2CO3 and OSA which were 2.25% and 6.19%, respectively. 35663757 10 7 from surfactant 1419:1428 arg1 production 1452:1461 oleogel production 1444:1461 oleogel production 1444:1461 PGOS can be used as a surfactant or gelator in oleogel production. 35663757 7 8 theme angle 1019:1023 arg1 Degree 967:972 Degree 967:972 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity 967:1048 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity confirmed that OSA substitution occurred in PG. 35663757 8 9 theme contact 1231:1237 arg1 angle 1239:1243 contact angle 1231:1243 contact angle 1231:1243 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 4 10 theme two-factor 569:578 arg1 CCD 606:608 CCD 606:608 CCD 606:608 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 4 10 theme two-factor 569:578 arg1 design 598:603 a two-factor central composite design 567:603 a two-factor central composite design (CCD) 567:609 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 4 10 theme two-factor 569:578 arg1 concentration 619:631 concentration 619:631 concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%) 619:676 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 0 11 theme glucomannan 107:117 arg1 stability 51:59 stability 51:59 stability 51:59 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 0 11 theme glucomannan 107:117 arg1 capacity 38:45 oil-in-water emulsion capacity 16:45 oil-in-water emulsion capacity 16:45 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 6 12 theme emulsion 843:850 arg1 capacity 852:859 the highest emulsion capacity 831:859 the highest emulsion capacity 831:859 The optimum conditions that resulted in the highest emulsion capacity and stability were obtained at concentrations of Na2CO3 and OSA which were 2.25% and 6.19%, respectively. 35663757 10 13 used used 1409:1412 arg2 gelator 1433:1439 gelator 1433:1439 gelator 1433:1439 PGOS can be used as a surfactant or gelator in oleogel production. 35663757 10 13 used used 1409:1412 arg2 PGOS 1397:1400 PGOS 1397:1400 PGOS 1397:1400 PGOS can be used as a surfactant or gelator in oleogel production. 35663757 10 13 used used 1409:1412 arg2 surfactant 1419:1428 surfactant 1419:1428 surfactant 1419:1428 PGOS can be used as a surfactant or gelator in oleogel production. 35663757 6 14 theme highest 835:841 arg1 capacity 852:859 the highest emulsion capacity 831:859 the highest emulsion capacity 831:859 The optimum conditions that resulted in the highest emulsion capacity and stability were obtained at concentrations of Na2CO3 and OSA which were 2.25% and 6.19%, respectively. 35663757 1 15 used used 168:171 arg2 Surfactants 152:162 Surfactants 152:162 Surfactants 152:162 Surfactants are used to reduce surface and interfacial tension to form emulsions. 35663757 1 16 theme interfacial 195:205 arg1 tension 207:213 surface and interfacial tension 183:213 tension 207:213 Surfactants are used to reduce surface and interfacial tension to form emulsions. 35663757 1 17 theme surface 183:189 arg1 tension 207:213 surface and interfacial tension 183:213 tension 207:213 Surfactants are used to reduce surface and interfacial tension to form emulsions. 35663757 5 18 theme OSA 734:736 arg1 concentration 706:718 the concentration 702:718 the concentration of Na2CO3 and OSA 702:736 The result showed that the concentration of Na2CO3 and OSA strongly influences emulsion capacity and stability. 35663757 10 19 dep surfactant 1419:1428 arg1 a 1417:1417 a 1417:1417 a 1417:1417 PGOS can be used as a surfactant or gelator in oleogel production. 35663757 7 20 theme contact 1011:1017 arg1 angle 1019:1023 contact angle 1011:1023 contact angle 1011:1023 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity confirmed that OSA substitution occurred in PG. 35663757 8 21 theme angle 1239:1243 arg1 Degree 1202:1207 Degree 1202:1207 Degree of Substitution (DS), contact angle, and viscosity 1202:1258 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 21 theme angle 1239:1243 arg1 characteristics 1102:1116 The characteristics 1098:1116 The characteristics of OSA-modified porang glucomannan (PGOS) such as 1098:1166 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 3 22 theme carbonate 390:398 arg1 concentration 366:378 the concentration 362:378 the concentration of sodium carbonate (Na2CO3) and octenyl succinic anhydride (OSA) in modifying PG using a microwave 362:478 This research aimed to optimize the concentration of sodium carbonate (Na2CO3) and octenyl succinic anhydride (OSA) in modifying PG using a microwave. 35663757 7 23 theme FTIR 996:999 arg1 analysis 1001:1008 FTIR analysis 996:1008 FTIR analysis 996:1008 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity confirmed that OSA substitution occurred in PG. 35663757 8 24 theme viscosity 1250:1258 arg1 Degree 1202:1207 Degree 1202:1207 Degree of Substitution (DS), contact angle, and viscosity 1202:1258 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 24 theme viscosity 1250:1258 arg1 characteristics 1102:1116 The characteristics 1098:1116 The characteristics of OSA-modified porang glucomannan (PGOS) such as 1098:1166 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 25 dep characteristics 1102:1116 arg1 characteristics 1102:1116 The characteristics 1098:1116 The characteristics of OSA-modified porang glucomannan (PGOS) such as 1098:1166 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 25 dep characteristics 1102:1116 arg1 stability 1191:1199 stability 1191:1199 stability 1191:1199 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 25 dep characteristics 1102:1116 arg1 capacity 1178:1185 emulsion capacity 1169:1185 emulsion capacity 1169:1185 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 3 26 theme succinic 421:428 arg1 OSA 441:443 OSA 441:443 OSA 441:443 This research aimed to optimize the concentration of sodium carbonate (Na2CO3) and octenyl succinic anhydride (OSA) in modifying PG using a microwave. 35663757 3 26 theme succinic 421:428 arg1 anhydride 430:438 octenyl succinic anhydride 413:438 octenyl succinic anhydride (OSA) 413:444 This research aimed to optimize the concentration of sodium carbonate (Na2CO3) and octenyl succinic anhydride (OSA) in modifying PG using a microwave. 35663757 7 27 theme OSA 1065:1067 arg1 substitution 1069:1080 OSA substitution 1065:1080 OSA substitution 1065:1080 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity confirmed that OSA substitution occurred in PG. 35663757 7 28 theme analysis 1001:1008 arg1 Degree 967:972 Degree 967:972 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity 967:1048 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity confirmed that OSA substitution occurred in PG. 35663757 3 29 theme anhydride 430:438 arg1 concentration 366:378 the concentration 362:378 the concentration of sodium carbonate (Na2CO3) and octenyl succinic anhydride (OSA) in modifying PG using a microwave 362:478 This research aimed to optimize the concentration of sodium carbonate (Na2CO3) and octenyl succinic anhydride (OSA) in modifying PG using a microwave. 35663757 0 30 theme emulsion 29:36 arg1 capacity 38:45 oil-in-water emulsion capacity 16:45 oil-in-water emulsion capacity 16:45 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 4 31 theme surface 536:542 arg1 methodology 544:554 response surface methodology 527:554 response surface methodology (RSM) 527:560 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 4 31 theme surface 536:542 arg1 RSM 557:559 RSM 557:559 RSM 557:559 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 9 32 attach presence 1354:1361 arg2 substitution 1370:1381 OSA substitution 1366:1381 OSA substitution 1366:1381 FT-IR analysis confirmed the presence of OSA substitution at 1734 cm-1. 35663757 9 32 attach presence 1354:1361 arg1 cm-1 1391:1394 1734 cm-1 1386:1394 1734 cm-1 1386:1394 FT-IR analysis confirmed the presence of OSA substitution at 1734 cm-1. 35663757 10 33 from gelator 1433:1439 arg1 production 1452:1461 oleogel production 1444:1461 oleogel production 1444:1461 PGOS can be used as a surfactant or gelator in oleogel production. 35663757 8 34 theme emulsion 1169:1176 arg1 characteristics 1102:1116 The characteristics 1098:1116 The characteristics of OSA-modified porang glucomannan (PGOS) such as 1098:1166 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 34 theme emulsion 1169:1176 arg1 capacity 1178:1185 emulsion capacity 1169:1185 emulsion capacity 1169:1185 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 3 35 theme sodium 383:388 arg1 carbonate 390:398 sodium carbonate 383:398 sodium carbonate (Na2CO3) 383:407 This research aimed to optimize the concentration of sodium carbonate (Na2CO3) and octenyl succinic anhydride (OSA) in modifying PG using a microwave. 35663757 3 35 theme sodium 383:388 arg1 Na2CO3 401:406 Na2CO3 401:406 Na2CO3 401:406 This research aimed to optimize the concentration of sodium carbonate (Na2CO3) and octenyl succinic anhydride (OSA) in modifying PG using a microwave. 35663757 2 36 theme high 287:290 arg1 viscosity 292:300 high viscosity 287:300 high viscosity 287:300 Polysaccharides such as Porang Glucomannan (PG) with high viscosity can be used as surfactants. 35663757 9 37 theme substitution 1370:1381 arg1 presence 1354:1361 the presence 1350:1361 the presence of OSA substitution at 1734 cm-1 1350:1394 FT-IR analysis confirmed the presence of OSA substitution at 1734 cm-1. 35663757 8 38 theme porang 1134:1139 arg1 PGOS 1154:1157 PGOS 1154:1157 PGOS 1154:1157 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 38 theme porang 1134:1139 arg1 glucomannan 1141:1151 OSA-modified porang glucomannan 1121:1151 OSA-modified porang glucomannan (PGOS) 1121:1158 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 6 39 theme Na2CO3 910:915 arg1 concentrations 892:905 concentrations 892:905 concentrations of Na2CO3 and OSA which were 2.25% and 6.19%, respectively 892:964 The optimum conditions that resulted in the highest emulsion capacity and stability were obtained at concentrations of Na2CO3 and OSA which were 2.25% and 6.19%, respectively. 35663757 2 40 theme Porang 258:263 arg1 PG 278:279 PG 278:279 PG 278:279 Polysaccharides such as Porang Glucomannan (PG) with high viscosity can be used as surfactants. 35663757 2 40 theme Porang 258:263 arg1 Glucomannan 265:275 Porang Glucomannan 258:275 Porang Glucomannan (PG) with high viscosity 258:300 Polysaccharides such as Porang Glucomannan (PG) with high viscosity can be used as surfactants. 35663757 4 41 theme Na2CO3 636:641 arg1 design 598:603 a two-factor central composite design 567:603 a two-factor central composite design (CCD) 567:609 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 4 41 theme Na2CO3 636:641 arg1 concentration 619:631 concentration 619:631 concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%) 619:676 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 0 42 theme capacity 38:45 arg1 Optimization 0:11 Optimization 0:11 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 0:150 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 3 43 theme octenyl 413:419 arg1 OSA 441:443 OSA 441:443 OSA 441:443 This research aimed to optimize the concentration of sodium carbonate (Na2CO3) and octenyl succinic anhydride (OSA) in modifying PG using a microwave. 35663757 3 43 theme octenyl 413:419 arg1 anhydride 430:438 octenyl succinic anhydride 413:438 octenyl succinic anhydride (OSA) 413:444 This research aimed to optimize the concentration of sodium carbonate (Na2CO3) and octenyl succinic anhydride (OSA) in modifying PG using a microwave. 35663757 5 44 theme emulsion 758:765 arg1 capacity 767:774 emulsion capacity 758:774 emulsion capacity 758:774 The result showed that the concentration of Na2CO3 and OSA strongly influences emulsion capacity and stability. 35663757 7 45 theme viscosity 1040:1048 arg1 Degree 967:972 Degree 967:972 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity 967:1048 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity confirmed that OSA substitution occurred in PG. 35663757 2 46 with Glucomannan 265:275 arg1 viscosity 292:300 high viscosity 287:300 high viscosity 287:300 Polysaccharides such as Porang Glucomannan (PG) with high viscosity can be used as surfactants. 35663757 8 47 theme OSA-modified 1121:1132 arg1 PGOS 1154:1157 PGOS 1154:1157 PGOS 1154:1157 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 47 theme OSA-modified 1121:1132 arg1 glucomannan 1141:1151 OSA-modified porang glucomannan 1121:1151 OSA-modified porang glucomannan (PGOS) 1121:1158 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 6 48 theme OSA 921:923 arg1 concentrations 892:905 concentrations 892:905 concentrations of Na2CO3 and OSA which were 2.25% and 6.19%, respectively 892:964 The optimum conditions that resulted in the highest emulsion capacity and stability were obtained at concentrations of Na2CO3 and OSA which were 2.25% and 6.19%, respectively. 35663757 9 49 theme FT-IR 1325:1329 arg1 analysis 1331:1338 FT-IR analysis 1325:1338 FT-IR analysis 1325:1338 FT-IR analysis confirmed the presence of OSA substitution at 1734 cm-1. 35663757 0 50 theme stability 51:59 arg1 Optimization 0:11 Optimization 0:11 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 0:150 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 4 51 theme response 527:534 arg1 methodology 544:554 response surface methodology 527:554 response surface methodology (RSM) 527:560 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 4 51 theme response 527:534 arg1 RSM 557:559 RSM 557:559 RSM 557:559 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 7 52 theme Substitution 977:988 arg1 Degree 967:972 Degree 967:972 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity 967:1048 Degree of Substitution (DS), FTIR analysis, contact angle, and increased viscosity confirmed that OSA substitution occurred in PG. 35663757 4 53 theme OSA 661:663 arg1 design 598:603 a two-factor central composite design 567:603 a two-factor central composite design (CCD) 567:609 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 4 53 theme OSA 661:663 arg1 concentration 619:631 concentration 619:631 concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%) 619:676 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 5 54 theme Na2CO3 723:728 arg1 concentration 706:718 the concentration 702:718 the concentration of Na2CO3 and OSA 702:736 The result showed that the concentration of Na2CO3 and OSA strongly influences emulsion capacity and stability. 35663757 2 55 used used 309:312 arg2 surfactants 317:327 surfactants 317:327 surfactants 317:327 Polysaccharides such as Porang Glucomannan (PG) with high viscosity can be used as surfactants. 35663757 2 55 used used 309:312 arg2 Polysaccharides 234:248 Polysaccharides 234:248 Polysaccharides such as Porang Glucomannan (PG) with high viscosity 234:300 Polysaccharides such as Porang Glucomannan (PG) with high viscosity can be used as surfactants. 35663757 2 55 used used 309:312 arg2 Glucomannan 265:275 Porang Glucomannan 258:275 Porang Glucomannan (PG) with high viscosity 258:300 Polysaccharides such as Porang Glucomannan (PG) with high viscosity can be used as surfactants. 35663757 4 56 theme composite 588:596 arg1 CCD 606:608 CCD 606:608 CCD 606:608 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 4 56 theme composite 588:596 arg1 design 598:603 a two-factor central composite design 567:603 a two-factor central composite design (CCD) 567:609 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 4 56 theme composite 588:596 arg1 concentration 619:631 concentration 619:631 concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%) 619:676 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 10 57 theme oleogel 1444:1450 arg1 production 1452:1461 oleogel production 1444:1461 oleogel production 1444:1461 PGOS can be used as a surfactant or gelator in oleogel production. 35663757 4 58 theme central 580:586 arg1 CCD 606:608 CCD 606:608 CCD 606:608 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 4 58 theme central 580:586 arg1 design 598:603 a two-factor central composite design 567:603 a two-factor central composite design (CCD) 567:609 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 4 58 theme central 580:586 arg1 concentration 619:631 concentration 619:631 concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%) 619:676 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 0 59 theme succinic 72:79 arg1 Blume 144:148 Blume 144:148 Blume 144:148 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 0 59 theme succinic 72:79 arg1 glucomannan 107:117 octenyl succinic anhydride-modified porang glucomannan 64:117 octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume) 64:149 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 0 60 theme octenyl 64:70 arg1 Blume 144:148 Blume 144:148 Blume 144:148 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 0 60 theme octenyl 64:70 arg1 glucomannan 107:117 octenyl succinic anhydride-modified porang glucomannan 64:117 octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume) 64:149 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 4 61 theme optimization 485:496 arg1 process 498:504 The optimization process 481:504 The optimization process 481:504 The optimization process is carried out using response surface methodology (RSM) with a two-factor central composite design (CCD), namely concentration of Na2CO3 (0.17-5.834%) and OSA (2.17-7.83%). 35663757 0 62 theme oil-in-water 16:27 arg1 capacity 38:45 oil-in-water emulsion capacity 16:45 oil-in-water emulsion capacity 16:45 Optimization of oil-in-water emulsion capacity and stability of octenyl succinic anhydride-modified porang glucomannan (Amorphophallus muelleri Blume). 35663757 8 63 theme Substitution 1212:1223 arg1 Degree 1202:1207 Degree 1202:1207 Degree of Substitution (DS), contact angle, and viscosity 1202:1258 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 8 63 theme Substitution 1212:1223 arg1 characteristics 1102:1116 The characteristics 1098:1116 The characteristics of OSA-modified porang glucomannan (PGOS) such as 1098:1166 The characteristics of OSA-modified porang glucomannan (PGOS) such as: emulsion capacity and stability, Degree of Substitution (DS), contact angle, and viscosity increased to 34.6% and 32.5%, 1.02%, 92o, 5720 cP, respectively. 35663757 9 64 from cm-1 1391:1394 arg1 presence 1354:1361 the presence 1350:1361 the presence of OSA substitution at 1734 cm-1 1350:1394 FT-IR analysis confirmed the presence of OSA substitution at 1734 cm-1. 36559240 5 0 theme edge 1000:1003 arg1 tension 1005:1011 pore edge tension 995:1011 pore edge tension 995:1011 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 0 1 theme Activity 93:100 arg1 Biomaterial 64:74 a Biomaterial 62:74 a Biomaterial of Antibacterial Activity 62:100 Complexation of a Polypeptide-Polyelectrolytes Bioparticle as a Biomaterial of Antibacterial Activity. 36559240 5 2 theme tension 1005:1011 arg1 increase 983:990 Significant increase 971:990 Significant increase of pore edge tension in giant vesicles 971:1029 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 6 3 theme Antibacterial 1121:1133 arg1 activity 1135:1142 Antibacterial activity 1121:1142 Antibacterial activity against Aeromonas dhakensis 1121:1170 Antibacterial activity against Aeromonas dhakensis was effective at 0.1% and equal for the isolated polypeptide and the same complexed in bioparticle, which opens perspectives to the composite material as an applicable antibacterial system. 36559240 4 4 with microparticles 806:819 arg1 polydispersity 832:845 polydispersity 832:845 polydispersity 832:845 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 4 4 with microparticles 806:819 arg1 potential 856:864 zeta potential 851:864 zeta potential 851:864 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 4 4 with microparticles 806:819 arg1 size 826:829 size 826:829 size 826:829 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 4 5 theme bioparticles 775:786 arg1 structure 750:758 colloidal structure 740:758 colloidal structure of redispersed bioparticles 740:786 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 3 6 theme complexation 606:617 arg1 complexation 606:617 complexation 606:617 complexation 606:617 The inclusion of the polypeptide in the bioparticle structure largely increases the binding sites of complexation during the bioparticles production, leading to its effective incorporation. 36559240 3 6 theme complexation 606:617 arg1 sites 597:601 the binding sites 585:601 the binding sites of complexation 585:617 The inclusion of the polypeptide in the bioparticle structure largely increases the binding sites of complexation during the bioparticles production, leading to its effective incorporation. 36559240 3 7 theme bioparticles 630:641 arg1 production 643:652 the bioparticles production 626:652 the bioparticles production 626:652 The inclusion of the polypeptide in the bioparticle structure largely increases the binding sites of complexation during the bioparticles production, leading to its effective incorporation. 36559240 6 8 theme composite 1304:1312 arg1 material 1314:1321 the composite material 1300:1321 the composite material 1300:1321 Antibacterial activity against Aeromonas dhakensis was effective at 0.1% and equal for the isolated polypeptide and the same complexed in bioparticle, which opens perspectives to the composite material as an applicable antibacterial system. 36559240 6 9 theme applicable 1329:1338 arg1 perspectives 1284:1295 perspectives 1284:1295 perspectives to the composite material 1284:1321 Antibacterial activity against Aeromonas dhakensis was effective at 0.1% and equal for the isolated polypeptide and the same complexed in bioparticle, which opens perspectives to the composite material as an applicable antibacterial system. 36559240 6 9 theme applicable 1329:1338 arg1 system 1354:1359 an applicable antibacterial system 1326:1359 an applicable antibacterial system 1326:1359 Antibacterial activity against Aeromonas dhakensis was effective at 0.1% and equal for the isolated polypeptide and the same complexed in bioparticle, which opens perspectives to the composite material as an applicable antibacterial system. 36559240 4 10 theme dependent 866:874 arg1 size 826:829 size 826:829 size 826:829 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 4 11 with nano 798:801 arg1 polydispersity 832:845 polydispersity 832:845 polydispersity 832:845 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 4 11 with nano 798:801 arg1 potential 856:864 zeta potential 851:864 zeta potential 851:864 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 4 11 with nano 798:801 arg1 size 826:829 size 826:829 size 826:829 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 1 12 theme interest 225:232 arg1 strategy 196:203 a strategy 194:203 a strategy of high and current interest 194:232 The development of biomaterials to enable application of antimicrobial peptides represents a strategy of high and current interest. 36559240 5 13 theme lipid 1099:1103 arg1 membrane 1111:1118 lipid model membrane 1099:1118 lipid model membrane 1099:1118 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 4 14 theme redispersed 763:773 arg1 bioparticles 775:786 redispersed bioparticles 763:786 redispersed bioparticles 763:786 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 4 15 theme structure 750:758 arg1 evaluation 726:735 detailed evaluation 717:735 detailed evaluation of colloidal structure of redispersed bioparticles 717:786 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 5 16 theme model 1105:1109 arg1 membrane 1111:1118 lipid model membrane 1099:1118 lipid model membrane 1099:1118 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 6 17 theme isolated 1212:1219 arg1 polypeptide 1221:1231 the isolated polypeptide 1208:1231 the isolated polypeptide 1208:1231 Antibacterial activity against Aeromonas dhakensis was effective at 0.1% and equal for the isolated polypeptide and the same complexed in bioparticle, which opens perspectives to the composite material as an applicable antibacterial system. 36559240 4 18 theme colloidal 740:748 arg1 structure 750:758 colloidal structure 740:758 colloidal structure of redispersed bioparticles 740:786 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 4 19 theme polypeptide 948:958 arg1 inclusion 960:968 the polypeptide inclusion 944:968 the polypeptide inclusion 944:968 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 5 20 theme effective 1041:1049 arg1 interaction 1051:1061 effective interaction 1041:1061 effective interaction of the polypeptide-bioparticle with lipid model membrane 1041:1118 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 1 21 theme high 208:211 arg1 interest 225:232 high and current interest 208:232 high and current interest 208:232 The development of biomaterials to enable application of antimicrobial peptides represents a strategy of high and current interest. 36559240 6 22 from % 1192:1192 arg1 effective 1176:1184 effective 1176:1184 effective 1176:1184 Antibacterial activity against Aeromonas dhakensis was effective at 0.1% and equal for the isolated polypeptide and the same complexed in bioparticle, which opens perspectives to the composite material as an applicable antibacterial system. 36559240 5 23 from increase 983:990 arg1 vesicles 1022:1029 giant vesicles 1016:1029 giant vesicles 1016:1029 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 2 24 theme properties 493:502 arg1 complex 468:474 a colloidal polyelectrolytic complex 439:474 a colloidal polyelectrolytic complex of pH-responsive properties 439:502 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 2 25 dep polysaccharides 374:388 arg1 polysaccharides 374:388 the biocompatible and biodegradable polysaccharides 338:388 the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate 338:421 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 2 25 dep polysaccharides 374:388 arg1 alginate 414:421 alginate 414:421 alginate 414:421 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 2 25 dep polysaccharides 374:388 arg1 chitosan-N-arginine 390:408 chitosan-N-arginine 390:408 chitosan-N-arginine 390:408 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 1 26 theme current 217:223 arg1 interest 225:232 high and current interest 208:232 high and current interest 208:232 The development of biomaterials to enable application of antimicrobial peptides represents a strategy of high and current interest. 36559240 2 27 theme pH-responsive 479:491 arg1 properties 493:502 pH-responsive properties 479:502 pH-responsive properties 479:502 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 1 28 theme biomaterials 122:133 arg1 development 107:117 The development 103:117 The development of biomaterials to enable application of antimicrobial peptides 103:181 The development of biomaterials to enable application of antimicrobial peptides represents a strategy of high and current interest. 36559240 3 29 theme polypeptide 526:536 arg1 inclusion 509:517 The inclusion 505:517 The inclusion of the polypeptide in the bioparticle structure 505:565 The inclusion of the polypeptide in the bioparticle structure largely increases the binding sites of complexation during the bioparticles production, leading to its effective incorporation. 36559240 5 30 theme polypeptide-bioparticle 1070:1092 arg1 interaction 1051:1061 effective interaction 1041:1061 effective interaction of the polypeptide-bioparticle with lipid model membrane 1041:1118 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 2 31 theme polyelectrolytic 451:466 arg1 complex 468:474 a colloidal polyelectrolytic complex 439:474 a colloidal polyelectrolytic complex of pH-responsive properties 439:502 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 0 32 theme Bioparticle 47:57 arg1 Complexation 0:11 Complexation 0:11 Complexation of a Polypeptide-Polyelectrolytes Bioparticle as a Biomaterial of Antibacterial Activity. 0:101 Complexation of a Polypeptide-Polyelectrolytes Bioparticle as a Biomaterial of Antibacterial Activity. 36559240 5 33 theme Significant 971:981 arg1 increase 983:990 Significant increase 971:990 Significant increase of pore edge tension in giant vesicles 971:1029 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 0 34 theme Polypeptide-Polyelectrolytes 18:45 arg1 Bioparticle 47:57 a Polypeptide-Polyelectrolytes Bioparticle 16:57 a Polypeptide-Polyelectrolytes Bioparticle 16:57 Complexation of a Polypeptide-Polyelectrolytes Bioparticle as a Biomaterial of Antibacterial Activity. 36559240 3 35 from inclusion 509:517 arg1 structure 557:565 the bioparticle structure 541:565 the bioparticle structure 541:565 The inclusion of the polypeptide in the bioparticle structure largely increases the binding sites of complexation during the bioparticles production, leading to its effective incorporation. 36559240 2 36 theme colloidal 441:449 arg1 complex 468:474 a colloidal polyelectrolytic complex 439:474 a colloidal polyelectrolytic complex of pH-responsive properties 439:502 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 3 37 theme bioparticle 545:555 arg1 structure 557:565 the bioparticle structure 541:565 the bioparticle structure 541:565 The inclusion of the polypeptide in the bioparticle structure largely increases the binding sites of complexation during the bioparticles production, leading to its effective incorporation. 36559240 1 38 theme peptides 174:181 arg1 application 145:155 application 145:155 application of antimicrobial peptides 145:181 The development of biomaterials to enable application of antimicrobial peptides represents a strategy of high and current interest. 36559240 2 39 theme biodegradable 360:372 arg1 polysaccharides 374:388 the biocompatible and biodegradable polysaccharides 338:388 the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate 338:421 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 2 39 theme biodegradable 360:372 arg1 alginate 414:421 alginate 414:421 alginate 414:421 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 2 39 theme biodegradable 360:372 arg1 chitosan-N-arginine 390:408 chitosan-N-arginine 390:408 chitosan-N-arginine 390:408 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 2 40 theme antimicrobial 308:320 arg1 polypeptide 322:332 an antimicrobial polypeptide 305:332 an antimicrobial polypeptide 305:332 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 5 41 theme giant 1016:1020 arg1 vesicles 1022:1029 giant vesicles 1016:1029 giant vesicles 1016:1029 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 6 42 theme antibacterial 1340:1352 arg1 perspectives 1284:1295 perspectives 1284:1295 perspectives to the composite material 1284:1321 Antibacterial activity against Aeromonas dhakensis was effective at 0.1% and equal for the isolated polypeptide and the same complexed in bioparticle, which opens perspectives to the composite material as an applicable antibacterial system. 36559240 6 42 theme antibacterial 1340:1352 arg1 system 1354:1359 an applicable antibacterial system 1326:1359 an applicable antibacterial system 1326:1359 Antibacterial activity against Aeromonas dhakensis was effective at 0.1% and equal for the isolated polypeptide and the same complexed in bioparticle, which opens perspectives to the composite material as an applicable antibacterial system. 36559240 3 43 theme effective 670:678 arg1 incorporation 680:692 its effective incorporation 666:692 its effective incorporation 666:692 The inclusion of the polypeptide in the bioparticle structure largely increases the binding sites of complexation during the bioparticles production, leading to its effective incorporation. 36559240 4 44 theme ionic 886:890 arg1 strength 892:899 ionic strength 886:899 ionic strength 886:899 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 4 45 theme zeta 851:854 arg1 potential 856:864 zeta potential 851:864 zeta potential 851:864 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 2 46 theme biocompatible 342:354 arg1 polysaccharides 374:388 the biocompatible and biodegradable polysaccharides 338:388 the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate 338:421 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 2 46 theme biocompatible 342:354 arg1 alginate 414:421 alginate 414:421 alginate 414:421 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 2 46 theme biocompatible 342:354 arg1 chitosan-N-arginine 390:408 chitosan-N-arginine 390:408 chitosan-N-arginine 390:408 In this study, a bioparticle was produced by the complexation between an antimicrobial polypeptide and the biocompatible and biodegradable polysaccharides chitosan-N-arginine and alginate, giving rise to a colloidal polyelectrolytic complex of pH-responsive properties. 36559240 0 47 theme Antibacterial 79:91 arg1 Activity 93:100 Antibacterial Activity 79:100 Antibacterial Activity 79:100 Complexation of a Polypeptide-Polyelectrolytes Bioparticle as a Biomaterial of Antibacterial Activity. 36559240 5 48 theme pore 995:998 arg1 tension 1005:1011 pore edge tension 995:1011 pore edge tension 995:1011 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 4 49 theme detailed 717:724 arg1 evaluation 726:735 detailed evaluation 717:735 detailed evaluation of colloidal structure of redispersed bioparticles 717:786 After lyophilization, detailed evaluation of colloidal structure of redispersed bioparticles evidenced nano or microparticles with size, polydispersity and zeta potential dependent on pH and ionic strength, and the dependence was not withdrawn with the polypeptide inclusion. 36559240 1 50 theme antimicrobial 160:172 arg1 peptides 174:181 antimicrobial peptides 160:181 antimicrobial peptides 160:181 The development of biomaterials to enable application of antimicrobial peptides represents a strategy of high and current interest. 36559240 5 51 with interaction 1051:1061 arg1 membrane 1111:1118 lipid model membrane 1099:1118 lipid model membrane 1099:1118 Significant increase of pore edge tension in giant vesicles evidenced effective interaction of the polypeptide-bioparticle with lipid model membrane. 36559240 3 52 theme binding 589:595 arg1 complexation 606:617 complexation 606:617 complexation 606:617 The inclusion of the polypeptide in the bioparticle structure largely increases the binding sites of complexation during the bioparticles production, leading to its effective incorporation. 36559240 3 52 theme binding 589:595 arg1 sites 597:601 the binding sites 585:601 the binding sites of complexation 585:617 The inclusion of the polypeptide in the bioparticle structure largely increases the binding sites of complexation during the bioparticles production, leading to its effective incorporation. 36370942 6 0 theme positive 1167:1174 arg1 effect 1176:1181 a positive effect 1165:1181 a positive effect 1165:1181 Thus, Fe3O4@PANI has been demonstrated to have a positive effect on the formation and stability of AGS. 36370942 2 1 theme Fe3O4 335:339 arg1 polyaniline 322:332 magnetic Fe3O4@polyaniline 307:332 magnetic Fe3O4@polyaniline (Fe3O4@PANI) 307:345 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 1 theme Fe3O4 335:339 arg1 PANI 341:344 Fe3O4@PANI 335:344 Fe3O4@PANI 335:344 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 2 theme granular 505:512 arg1 sludge 514:519 aerobic granular sludge 497:519 aerobic granular sludge (AGS) 497:525 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 2 theme granular 505:512 arg1 AGS 522:524 AGS 522:524 AGS 522:524 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 0 3 from effects 9:15 arg1 sludge 67:72 aerobic granular sludge 50:72 aerobic granular sludge 50:72 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 1 4 theme magnetic 154:161 arg1 material 163:170 The magnetic material 150:170 The magnetic material 150:170 The magnetic material has been determined to have a positive effect on sludge granulation and wastewater treatment performance. 36370942 1 5 theme wastewater 244:253 arg1 performance 265:275 wastewater treatment performance 244:275 wastewater treatment performance 244:275 The magnetic material has been determined to have a positive effect on sludge granulation and wastewater treatment performance. 36370942 3 6 theme AGS 639:641 arg1 formation 626:634 the formation 622:634 the formation of AGS 622:641 The results indicated that the composite combined the advantages of PANI and Fe3O4 to promote the formation of AGS during the granulation period. 36370942 4 7 theme AGS 841:843 arg1 stability 824:832 the stability 820:832 the stability of the AGS 820:843 The Fe3O4@PANI stimulated the granules to secrete extracellular polymeric substances with a higher proteins/polysaccharides ratio, thus enhancing the stability of the AGS. 36370942 6 8 theme Fe3O4 1124:1128 arg1 PANI 1130:1133 Fe3O4@PANI 1124:1133 Fe3O4@PANI 1124:1133 Thus, Fe3O4@PANI has been demonstrated to have a positive effect on the formation and stability of AGS. 36370942 2 9 from effect 297:302 arg1 performance 413:423 aerobic granulation, granule stability, and pollutants removal performance 350:423 aerobic granulation, granule stability, and pollutants removal performance 350:423 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 1 10 theme treatment 255:263 arg1 performance 265:275 wastewater treatment performance 244:275 wastewater treatment performance 244:275 The magnetic material has been determined to have a positive effect on sludge granulation and wastewater treatment performance. 36370942 0 11 theme Aerobic 75:81 arg1 granulation 83:93 Aerobic granulation 75:93 Aerobic granulation 75:93 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 11 theme Aerobic 75:81 arg1 effects 9:15 Positive effects 0:15 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 0:148 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 5 12 theme organisms 1065:1073 arg1 enrichment 1004:1013 the enrichment 1000:1013 the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI 1000:1115 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 0 13 theme granule 96:102 arg1 stability 104:112 granule stability 96:112 granule stability 96:112 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 13 theme granule 96:102 arg1 effects 9:15 Positive effects 0:15 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 0:148 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 5 14 theme microbial 859:867 arg1 analysis 879:886 microbial community analysis 859:886 microbial community analysis 859:886 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 5 15 theme AGS 931:933 arg1 performance 912:922 the great performance 902:922 the great performance of the AGS on denitrification and phosphorus removal 902:975 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 5 16 from removal 969:975 arg1 performance 912:922 the great performance 902:922 the great performance of the AGS on denitrification and phosphorus removal 902:975 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 2 17 theme granulation 358:368 arg1 performance 413:423 aerobic granulation, granule stability, and pollutants removal performance 350:423 aerobic granulation, granule stability, and pollutants removal performance 350:423 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 18 theme batch 470:474 arg1 reactor 476:482 a sequencing batch reactor 457:482 a sequencing batch reactor to cultivate aerobic granular sludge (AGS) 457:525 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 3 19 theme granulation 654:664 arg1 period 666:671 the granulation period 650:671 the granulation period 650:671 The results indicated that the composite combined the advantages of PANI and Fe3O4 to promote the formation of AGS during the granulation period. 36370942 2 20 theme removal 405:411 arg1 performance 413:423 aerobic granulation, granule stability, and pollutants removal performance 350:423 aerobic granulation, granule stability, and pollutants removal performance 350:423 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 5 21 from denitrification 938:952 arg1 performance 912:922 the great performance 902:922 the great performance of the AGS on denitrification and phosphorus removal 902:975 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 2 22 theme aerobic 350:356 arg1 granulation 358:368 aerobic granulation 350:368 aerobic granulation 350:368 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 0 23 theme granular 58:65 arg1 sludge 67:72 aerobic granular sludge 50:72 aerobic granular sludge 50:72 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 4 24 theme @ 683:683 arg1 PANI 684:687 The Fe3O4@PANI 674:687 The Fe3O4@PANI 674:687 The Fe3O4@PANI stimulated the granules to secrete extracellular polymeric substances with a higher proteins/polysaccharides ratio, thus enhancing the stability of the AGS. 36370942 0 25 theme Positive 0:7 arg1 granulation 83:93 Aerobic granulation 75:93 Aerobic granulation 75:93 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 25 theme Positive 0:7 arg1 stability 104:112 granule stability 96:112 granule stability 96:112 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 25 theme Positive 0:7 arg1 effects 9:15 Positive effects 0:15 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 0:148 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 25 theme Positive 0:7 arg1 performance 137:147 pollutants removal performance 118:147 pollutants removal performance 118:147 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 5 26 theme PAO 1099:1101 arg1 enrichment 1004:1013 the enrichment 1000:1013 the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI 1000:1115 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 4 27 theme Fe3O4 678:682 arg1 PANI 684:687 The Fe3O4@PANI 674:687 The Fe3O4@PANI 674:687 The Fe3O4@PANI stimulated the granules to secrete extracellular polymeric substances with a higher proteins/polysaccharides ratio, thus enhancing the stability of the AGS. 36370942 5 28 theme denitrifying 1086:1097 arg1 PAO 1099:1101 denitrifying PAO 1086:1101 denitrifying PAO by Fe3O4@PANI 1086:1115 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 0 29 theme magnetic 20:27 arg1 polyaniline 35:45 magnetic Fe3O4@polyaniline 20:45 magnetic Fe3O4@polyaniline 20:45 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 5 30 theme phosphorus 958:967 arg1 removal 969:975 phosphorus removal 958:975 phosphorus removal 958:975 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 5 31 theme accumulating 1052:1063 arg1 PAO 1076:1078 PAO 1076:1078 PAO 1076:1078 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 5 31 theme accumulating 1052:1063 arg1 organisms 1065:1073 phosphorus accumulating organisms 1041:1073 phosphorus accumulating organisms (PAO) 1041:1079 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 5 32 theme great 906:910 arg1 performance 912:922 the great performance 902:922 the great performance of the AGS on denitrification and phosphorus removal 902:975 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 6 33 contain have 1160:1163 arg1 PANI 1130:1133 Fe3O4@PANI 1124:1133 Fe3O4@PANI 1124:1133 Thus, Fe3O4@PANI has been demonstrated to have a positive effect on the formation and stability of AGS. 36370942 6 33 contain have 1160:1163 arg2 effect 1176:1181 a positive effect 1165:1181 a positive effect 1165:1181 Thus, Fe3O4@PANI has been demonstrated to have a positive effect on the formation and stability of AGS. 36370942 5 34 theme bacteria 1031:1038 arg1 enrichment 1004:1013 the enrichment 1000:1013 the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI 1000:1115 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 2 35 theme stability 379:387 arg1 performance 413:423 aerobic granulation, granule stability, and pollutants removal performance 350:423 aerobic granulation, granule stability, and pollutants removal performance 350:423 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 0 36 theme @ 34:34 arg1 polyaniline 35:45 magnetic Fe3O4@polyaniline 20:45 magnetic Fe3O4@polyaniline 20:45 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 5 37 theme community 869:877 arg1 analysis 879:886 microbial community analysis 859:886 microbial community analysis 859:886 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 0 38 theme removal 129:135 arg1 effects 9:15 Positive effects 0:15 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 0:148 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 38 theme removal 129:135 arg1 performance 137:147 pollutants removal performance 118:147 pollutants removal performance 118:147 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 3 39 theme Fe3O4 605:609 arg1 advantages 582:591 the advantages 578:591 the advantages of PANI and Fe3O4 578:609 The results indicated that the composite combined the advantages of PANI and Fe3O4 to promote the formation of AGS during the granulation period. 36370942 4 40 theme higher 766:771 arg1 ratio 798:802 a higher proteins/polysaccharides ratio 764:802 a higher proteins/polysaccharides ratio 764:802 The Fe3O4@PANI stimulated the granules to secrete extracellular polymeric substances with a higher proteins/polysaccharides ratio, thus enhancing the stability of the AGS. 36370942 2 41 theme granule 371:377 arg1 stability 379:387 granule stability 371:387 granule stability 371:387 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 0 42 theme Fe3O4 29:33 arg1 polyaniline 35:45 magnetic Fe3O4@polyaniline 20:45 magnetic Fe3O4@polyaniline 20:45 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 43 theme pollutants 118:127 arg1 effects 9:15 Positive effects 0:15 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 0:148 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 43 theme pollutants 118:127 arg1 performance 137:147 pollutants removal performance 118:147 pollutants removal performance 118:147 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 5 44 theme phosphorus 1041:1050 arg1 PAO 1076:1078 PAO 1076:1078 PAO 1076:1078 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 5 44 theme phosphorus 1041:1050 arg1 organisms 1065:1073 phosphorus accumulating organisms 1041:1073 phosphorus accumulating organisms (PAO) 1041:1079 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 2 45 theme pollutants 394:403 arg1 removal 405:411 pollutants removal 394:411 pollutants removal 394:411 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 46 theme aerobic 497:503 arg1 sludge 514:519 aerobic granular sludge 497:519 aerobic granular sludge (AGS) 497:525 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 46 theme aerobic 497:503 arg1 AGS 522:524 AGS 522:524 AGS 522:524 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 1 47 theme positive 202:209 arg1 effect 211:216 a positive effect 200:216 a positive effect 200:216 The magnetic material has been determined to have a positive effect on sludge granulation and wastewater treatment performance. 36370942 5 48 theme Fe3O4 1106:1110 arg1 PANI 1112:1115 Fe3O4@PANI 1106:1115 Fe3O4@PANI 1106:1115 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 3 49 theme PANI 596:599 arg1 advantages 582:591 the advantages 578:591 the advantages of PANI and Fe3O4 578:609 The results indicated that the composite combined the advantages of PANI and Fe3O4 to promote the formation of AGS during the granulation period. 36370942 2 50 theme polyaniline 322:332 arg1 effect 297:302 the effect 293:302 the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance 293:423 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 0 51 theme polyaniline 35:45 arg1 granulation 83:93 Aerobic granulation 75:93 Aerobic granulation 75:93 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 51 theme polyaniline 35:45 arg1 stability 104:112 granule stability 96:112 granule stability 96:112 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 51 theme polyaniline 35:45 arg1 effects 9:15 Positive effects 0:15 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 0:148 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 51 theme polyaniline 35:45 arg1 performance 137:147 pollutants removal performance 118:147 pollutants removal performance 118:147 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 5 52 theme @ 1111:1111 arg1 PANI 1112:1115 Fe3O4@PANI 1106:1115 Fe3O4@PANI 1106:1115 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 4 53 theme proteins/polysaccharides 773:796 arg1 ratio 798:802 a higher proteins/polysaccharides ratio 764:802 a higher proteins/polysaccharides ratio 764:802 The Fe3O4@PANI stimulated the granules to secrete extracellular polymeric substances with a higher proteins/polysaccharides ratio, thus enhancing the stability of the AGS. 36370942 2 54 theme @ 321:321 arg1 polyaniline 322:332 magnetic Fe3O4@polyaniline 307:332 magnetic Fe3O4@polyaniline (Fe3O4@PANI) 307:345 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 54 theme @ 321:321 arg1 PANI 341:344 Fe3O4@PANI 335:344 Fe3O4@PANI 335:344 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 4 55 theme polymeric 738:746 arg1 substances 748:757 extracellular polymeric substances 724:757 extracellular polymeric substances 724:757 The Fe3O4@PANI stimulated the granules to secrete extracellular polymeric substances with a higher proteins/polysaccharides ratio, thus enhancing the stability of the AGS. 36370942 2 56 theme Fe3O4 316:320 arg1 polyaniline 322:332 magnetic Fe3O4@polyaniline 307:332 magnetic Fe3O4@polyaniline (Fe3O4@PANI) 307:345 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 56 theme Fe3O4 316:320 arg1 PANI 341:344 Fe3O4@PANI 335:344 Fe3O4@PANI 335:344 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 5 57 from performance 912:922 arg1 denitrification 938:952 denitrification 938:952 denitrification 938:952 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 5 57 from performance 912:922 arg1 removal 969:975 phosphorus removal 958:975 phosphorus removal 958:975 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 6 58 theme AGS 1217:1219 arg1 stability 1204:1212 stability 1204:1212 stability 1204:1212 Thus, Fe3O4@PANI has been demonstrated to have a positive effect on the formation and stability of AGS. 36370942 6 58 theme AGS 1217:1219 arg1 formation 1190:1198 formation 1190:1198 formation 1190:1198 Thus, Fe3O4@PANI has been demonstrated to have a positive effect on the formation and stability of AGS. 36370942 1 59 contain have 195:198 arg2 effect 211:216 a positive effect 200:216 a positive effect 200:216 The magnetic material has been determined to have a positive effect on sludge granulation and wastewater treatment performance. 36370942 1 59 contain have 195:198 arg1 material 163:170 The magnetic material 150:170 The magnetic material 150:170 The magnetic material has been determined to have a positive effect on sludge granulation and wastewater treatment performance. 36370942 4 60 theme extracellular 724:736 arg1 substances 748:757 extracellular polymeric substances 724:757 extracellular polymeric substances 724:757 The Fe3O4@PANI stimulated the granules to secrete extracellular polymeric substances with a higher proteins/polysaccharides ratio, thus enhancing the stability of the AGS. 36370942 2 61 theme magnetic 307:314 arg1 polyaniline 322:332 magnetic Fe3O4@polyaniline 307:332 magnetic Fe3O4@polyaniline (Fe3O4@PANI) 307:345 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 61 theme magnetic 307:314 arg1 PANI 341:344 Fe3O4@PANI 335:344 Fe3O4@PANI 335:344 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 62 theme sequencing 459:468 arg1 reactor 476:482 a sequencing batch reactor 457:482 a sequencing batch reactor to cultivate aerobic granular sludge (AGS) 457:525 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 5 63 theme denitrifying 1018:1029 arg1 bacteria 1031:1038 denitrifying bacteria 1018:1038 denitrifying bacteria 1018:1038 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 0 64 dep effects 9:15 arg1 granulation 83:93 Aerobic granulation 75:93 Aerobic granulation 75:93 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 64 dep effects 9:15 arg1 stability 104:112 granule stability 96:112 granule stability 96:112 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 64 dep effects 9:15 arg1 effects 9:15 Positive effects 0:15 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 0:148 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 0 64 dep effects 9:15 arg1 performance 137:147 pollutants removal performance 118:147 pollutants removal performance 118:147 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 1 65 theme sludge 221:226 arg1 granulation 228:238 sludge granulation 221:238 sludge granulation 221:238 The magnetic material has been determined to have a positive effect on sludge granulation and wastewater treatment performance. 36370942 0 66 theme aerobic 50:56 arg1 sludge 67:72 aerobic granular sludge 50:72 aerobic granular sludge 50:72 Positive effects of magnetic Fe3O4@polyaniline on aerobic granular sludge: Aerobic granulation, granule stability and pollutants removal performance. 36370942 6 67 theme @ 1129:1129 arg1 PANI 1130:1133 Fe3O4@PANI 1124:1133 Fe3O4@PANI 1124:1133 Thus, Fe3O4@PANI has been demonstrated to have a positive effect on the formation and stability of AGS. 36370942 2 68 theme @ 340:340 arg1 polyaniline 322:332 magnetic Fe3O4@polyaniline 307:332 magnetic Fe3O4@polyaniline (Fe3O4@PANI) 307:345 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 2 68 theme @ 340:340 arg1 PANI 341:344 Fe3O4@PANI 335:344 Fe3O4@PANI 335:344 In this study, the effect of magnetic Fe3O4@polyaniline (Fe3O4@PANI) on aerobic granulation, granule stability, and pollutants removal performance was evaluated by adding it into a sequencing batch reactor to cultivate aerobic granular sludge (AGS). 36370942 5 69 from AGS 931:933 arg1 denitrification 938:952 denitrification 938:952 denitrification 938:952 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 5 69 from AGS 931:933 arg1 removal 969:975 phosphorus removal 958:975 phosphorus removal 958:975 In addition, microbial community analysis revealed that the great performance of the AGS on denitrification and phosphorus removal could be attributed to the enrichment of denitrifying bacteria, phosphorus accumulating organisms (PAO), and denitrifying PAO by Fe3O4@PANI. 36370942 6 70 dep formation 1190:1198 arg1 the 1186:1188 the 1186:1188 the 1186:1188 Thus, Fe3O4@PANI has been demonstrated to have a positive effect on the formation and stability of AGS. 37378543 9 0 theme N-linked 1145:1152 arg1 glycosylation 1154:1166 mature N-linked glycosylation 1138:1166 mature N-linked glycosylation 1138:1166 pUL49.5 promoted pUL10 expression and mature N-linked glycosylation modification. 37378543 2 1 theme cell-to-cell 285:296 arg1 spread 298:303 cell-to-cell spread 285:303 cell-to-cell spread 285:303 pUL10 plays complex roles in viral fusion, assembly, cell-to-cell spread, and immune evasion, which are closely related to its protein characteristics and partners. 37378543 9 2 link N-linked 1145:1152 arg1 glycosylation 1154:1166 mature N-linked glycosylation 1138:1166 mature N-linked glycosylation 1138:1166 pUL49.5 promoted pUL10 expression and mature N-linked glycosylation modification. 37378543 8 3 theme interaction 932:942 arg1 sites 944:948 multiple interaction sites 923:948 multiple interaction sites 923:948 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 13 4 theme DPV 1726:1728 arg1 protein 1735:1741 DPV UL10 protein 1726:1741 DPV UL10 protein (pUL10) 1726:1749 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 4 theme DPV 1726:1728 arg1 homolog 1756:1762 a homolog 1754:1762 a homolog 1754:1762 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 4 theme DPV 1726:1728 arg1 pUL10 1744:1748 pUL10 1744:1748 pUL10 1744:1748 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 1 5 theme subfamily 146:154 arg1 member 115:120 a member 113:120 a member of the alphaherpesvirus subfamily 113:154 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 5 theme subfamily 146:154 arg1 virus 98:102 Duck plague virus 86:102 Duck plague virus (DPV) 86:108 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 12 6 with disease 1551:1557 arg1 rates 1593:1597 high morbidity and mortality rates 1564:1597 high morbidity and mortality rates 1564:1597 IMPORTANCE Duck plague is a disease with high morbidity and mortality rates, and it causes great losses for the duck breeding industry. 37378543 10 7 theme DPV 1383:1385 arg1 pUL10 1387:1391 DPV pUL10 1383:1391 DPV pUL10 1383:1391 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 12 8 theme morbidity 1569:1577 arg1 rates 1593:1597 high morbidity and mortality rates 1564:1597 high morbidity and mortality rates 1564:1597 IMPORTANCE Duck plague is a disease with high morbidity and mortality rates, and it causes great losses for the duck breeding industry. 37378543 8 9 theme noncovalent 961:971 arg1 forces 973:978 noncovalent forces 961:978 noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains 961:1035 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 1 10 theme Duck 86:89 arg1 member 115:120 a member 113:120 a member of the alphaherpesvirus subfamily 113:154 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 10 theme Duck 86:89 arg1 DPV 105:107 DPV 105:107 DPV 105:107 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 10 theme Duck 86:89 arg1 virus 98:102 Duck plague virus 86:102 Duck plague virus (DPV) 86:108 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 2 11 theme complex 244:250 arg1 roles 252:256 complex roles 244:256 complex roles 244:256 pUL10 plays complex roles in viral fusion, assembly, cell-to-cell spread, and immune evasion, which are closely related to its protein characteristics and partners. 37378543 12 12 theme mortality 1583:1591 arg1 rates 1593:1597 high morbidity and mortality rates 1564:1597 high morbidity and mortality rates 1564:1597 IMPORTANCE Duck plague is a disease with high morbidity and mortality rates, and it causes great losses for the duck breeding industry. 37378543 4 13 theme localization 565:576 arg1 type 514:517 the type 510:517 the type of glycosylation modification and subcellular localization 510:576 In this study, we identified the characteristics of pUL10, such as the type of glycosylation modification and subcellular localization. 37378543 10 14 from deletion 1192:1199 arg1 DPV 1214:1216 DPV 1214:1216 DPV 1214:1216 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 10 15 theme UL49.5 1204:1209 arg1 deletion 1192:1199 deletion 1192:1199 deletion of UL49.5 in DPV 1192:1216 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 12 16 theme breeding 1640:1647 arg1 industry 1649:1656 the duck breeding industry 1631:1656 the duck breeding industry 1631:1656 IMPORTANCE Duck plague is a disease with high morbidity and mortality rates, and it causes great losses for the duck breeding industry. 37378543 13 17 theme Duck 1659:1662 arg1 agent 1700:1704 the causative agent 1686:1704 the causative agent of duck plague 1686:1719 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 17 theme Duck 1659:1662 arg1 DPV 1678:1680 DPV 1678:1680 DPV 1678:1680 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 17 theme Duck 1659:1662 arg1 virus 1671:1675 Duck plague virus 1659:1675 Duck plague virus (DPV) 1659:1681 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 11 18 theme glycosylation 1485:1497 arg1 effect 1469:1474 the effect 1465:1474 the effect of pUL10 glycosylation on virus proliferation 1465:1520 This study provides a basis for future exploration of the effect of pUL10 glycosylation on virus proliferation. 37378543 8 19 from bond 1062:1065 arg1 domains 1006:1012 the pUL49.5 N-terminal domains 983:1012 the pUL49.5 N-terminal domains 983:1012 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 8 19 from bond 1062:1065 arg1 domains 1029:1035 C-terminal domains 1018:1035 C-terminal domains 1018:1035 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 13 20 theme glycoprotein 1767:1778 arg1 gM 1783:1784 gM 1783:1784 gM 1783:1784 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 20 theme glycoprotein 1767:1778 arg1 M 1780:1780 glycoprotein M 1767:1780 glycoprotein M (gM) 1767:1785 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 5 21 theme viral 678:682 arg1 proteins 684:691 other viral proteins 672:691 other viral proteins that participate in pUL10 modification and localization 672:747 The characteristic differences in pUL10 in transfection and infection suggest that there are other viral proteins that participate in pUL10 modification and localization. 37378543 0 22 theme Duck 41:44 arg1 Virus 53:57 Duck Plague Virus pUL10 41:63 Duck Plague Virus pUL10 41:63 N-Linked Glycosylation and Expression of Duck Plague Virus pUL10 Promoted by pUL49.5. 37378543 10 23 theme pUL10 1247:1251 arg1 mass 1239:1242 the molecular mass 1225:1242 the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection 1225:1408 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 0 24 theme N-Linked 0:7 arg1 Glycosylation 9:21 N-Linked Glycosylation 0:21 N-Linked Glycosylation 0:21 N-Linked Glycosylation and Expression of Duck Plague Virus pUL10 Promoted by pUL49.5. 37378543 8 25 theme C-terminal 1018:1027 arg1 domains 1029:1035 C-terminal domains 1018:1035 C-terminal domains 1018:1035 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 11 26 from exploration 1450:1460 arg1 proliferation 1508:1520 virus proliferation 1502:1520 virus proliferation 1502:1520 This study provides a basis for future exploration of the effect of pUL10 glycosylation on virus proliferation. 37378543 2 27 theme protein 359:365 arg1 characteristics 367:381 its protein characteristics 355:381 its protein characteristics 355:381 pUL10 plays complex roles in viral fusion, assembly, cell-to-cell spread, and immune evasion, which are closely related to its protein characteristics and partners. 37378543 3 28 theme Few 397:399 arg1 studies 401:407 Few studies 397:407 Few studies 397:407 Few studies have been conducted on DPV pUL10. 37378543 8 29 theme covalent 1043:1050 arg1 bond 1062:1065 a covalent disulfide bond 1041:1065 a covalent disulfide bond between two conserved cysteines 1041:1097 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 6 30 theme pUL10 797:801 arg1 partner 786:792 the interaction partner 770:792 the interaction partner of pUL10 770:801 Therefore, pUL49.5, the interaction partner of pUL10, was explored. 37378543 6 30 theme pUL10 797:801 arg1 pUL49.5 761:767 pUL49.5 761:767 pUL49.5 761:767 Therefore, pUL49.5, the interaction partner of pUL10, was explored. 37378543 0 31 gly Glycosylation 9:21 arg1 Virus 53:57 Duck Plague Virus pUL10 41:63 Duck Plague Virus pUL10 41:63 N-Linked Glycosylation and Expression of Duck Plague Virus pUL10 Promoted by pUL49.5. 37378543 0 32 theme Plague 46:51 arg1 Virus 53:57 Duck Plague Virus pUL10 41:63 Duck Plague Virus pUL10 41:63 N-Linked Glycosylation and Expression of Duck Plague Virus pUL10 Promoted by pUL49.5. 37378543 14 33 theme viral 1854:1858 arg1 fusion 1860:1865 viral fusion 1854:1865 viral fusion 1854:1865 pUL10 plays complex roles in viral fusion, assembly, cell-to-cell spread, and immune evasion, which are closely related to its protein characteristics and partners. 37378543 1 34 theme conserved 182:190 arg1 protein 201:207 a conserved envelope protein 180:207 a conserved envelope protein 180:207 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 34 theme conserved 182:190 arg1 UL10 218:221 protein UL10 210:221 protein UL10 (pUL10) 210:229 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 34 theme conserved 182:190 arg1 genome 165:170 its genome 161:170 its genome 161:170 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 13 35 theme UL10 1730:1733 arg1 protein 1735:1741 DPV UL10 protein 1726:1741 DPV UL10 protein (pUL10) 1726:1749 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 35 theme UL10 1730:1733 arg1 homolog 1756:1762 a homolog 1754:1762 a homolog 1754:1762 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 35 theme UL10 1730:1733 arg1 pUL10 1744:1748 pUL10 1744:1748 pUL10 1744:1748 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 12 36 dep IMPORTANCE 1523:1532 arg1 plague 1539:1544 Duck plague 1534:1544 IMPORTANCE Duck plague 1523:1544 IMPORTANCE Duck plague is a disease with high morbidity and mortality rates, and it causes great losses for the duck breeding industry. 37378543 10 37 theme main 1331:1334 arg1 pUL49.5 1315:1321 pUL49.5 1315:1321 pUL49.5 1315:1321 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 10 37 theme main 1331:1334 arg1 factor 1336:1341 the main factor 1327:1341 the main factor affecting the N-linked glycosylation of DPV pUL10 during infection 1327:1408 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 9 38 theme mature 1138:1143 arg1 glycosylation 1154:1166 mature N-linked glycosylation 1138:1166 mature N-linked glycosylation 1138:1166 pUL49.5 promoted pUL10 expression and mature N-linked glycosylation modification. 37378543 1 39 theme protein 210:216 arg1 protein 201:207 a conserved envelope protein 180:207 a conserved envelope protein 180:207 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 39 theme protein 210:216 arg1 UL10 218:221 protein UL10 210:221 protein UL10 (pUL10) 210:229 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 39 theme protein 210:216 arg1 pUL10 224:228 pUL10 224:228 pUL10 224:228 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 8 40 theme multiple 923:930 arg1 sites 944:948 multiple interaction sites 923:948 multiple interaction sites 923:948 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 4 41 theme pUL10 495:499 arg1 type 514:517 the type 510:517 the type of glycosylation modification and subcellular localization 510:576 In this study, we identified the characteristics of pUL10, such as the type of glycosylation modification and subcellular localization. 37378543 4 41 theme pUL10 495:499 arg1 characteristics 476:490 the characteristics 472:490 the characteristics 472:490 In this study, we identified the characteristics of pUL10, such as the type of glycosylation modification and subcellular localization. 37378543 13 42 theme plague 1714:1719 arg1 agent 1700:1704 the causative agent 1686:1704 the causative agent of duck plague 1686:1719 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 42 theme plague 1714:1719 arg1 homolog 1756:1762 a homolog 1754:1762 a homolog 1754:1762 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 42 theme plague 1714:1719 arg1 virus 1671:1675 Duck plague virus 1659:1675 Duck plague virus (DPV) 1659:1681 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 42 theme plague 1714:1719 arg1 protein 1735:1741 DPV UL10 protein 1726:1741 DPV UL10 protein (pUL10) 1726:1749 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 5 43 theme characteristic 583:596 arg1 differences 598:608 The characteristic differences 579:608 The characteristic differences in pUL10 in transfection and infection 579:647 The characteristic differences in pUL10 in transfection and infection suggest that there are other viral proteins that participate in pUL10 modification and localization. 37378543 10 44 theme N-linked 1357:1364 arg1 glycosylation 1366:1378 the N-linked glycosylation 1353:1378 the N-linked glycosylation of DPV pUL10 during infection 1353:1408 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 11 45 theme virus 1502:1506 arg1 proliferation 1508:1520 virus proliferation 1502:1520 virus proliferation 1502:1520 This study provides a basis for future exploration of the effect of pUL10 glycosylation on virus proliferation. 37378543 1 46 theme alphaherpesvirus 129:144 arg1 subfamily 146:154 the alphaherpesvirus subfamily 125:154 the alphaherpesvirus subfamily 125:154 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 13 47 theme causative 1690:1698 arg1 agent 1700:1704 the causative agent 1686:1704 the causative agent of duck plague 1686:1719 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 47 theme causative 1690:1698 arg1 virus 1671:1675 Duck plague virus 1659:1675 Duck plague virus (DPV) 1659:1681 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 10 48 theme pUL10 1387:1391 arg1 glycosylation 1366:1378 the N-linked glycosylation 1353:1378 the N-linked glycosylation of DPV pUL10 during infection 1353:1408 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 2 49 theme viral 261:265 arg1 fusion 267:272 viral fusion 261:272 viral fusion 261:272 pUL10 plays complex roles in viral fusion, assembly, cell-to-cell spread, and immune evasion, which are closely related to its protein characteristics and partners. 37378543 11 50 gly glycosylation 1485:1497 arg1 virus 1502:1506 virus proliferation 1502:1520 virus proliferation 1502:1520 This study provides a basis for future exploration of the effect of pUL10 glycosylation on virus proliferation. 37378543 4 51 theme modification 536:547 arg1 type 514:517 the type 510:517 the type of glycosylation modification and subcellular localization 510:576 In this study, we identified the characteristics of pUL10, such as the type of glycosylation modification and subcellular localization. 37378543 11 52 theme effect 1469:1474 arg1 exploration 1450:1460 future exploration 1443:1460 future exploration of the effect of pUL10 glycosylation on virus proliferation 1443:1520 This study provides a basis for future exploration of the effect of pUL10 glycosylation on virus proliferation. 37378543 15 53 dep pUL49.5 2040:2046 arg1 partner 2051:2057 a partner 2049:2057 a partner of pUL10 2049:2066 In this study, we systematically explored whether pUL49.5 (a partner of pUL10) plays roles in the localization, modification, and expression of pUL10. 37378543 4 54 theme subcellular 553:563 arg1 localization 565:576 subcellular localization 553:576 subcellular localization 553:576 In this study, we identified the characteristics of pUL10, such as the type of glycosylation modification and subcellular localization. 37378543 10 55 dep approximately3 1268:1281 arg1 to 1283:1284 to 1283:1284 to 1283:1284 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 10 55 dep approximately3 1268:1281 arg1 10 kDa 1286:1291 10 kDa 1286:1291 10 kDa 1286:1291 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 12 56 theme high 1564:1567 arg1 morbidity 1569:1577 high morbidity 1564:1577 high morbidity 1564:1577 IMPORTANCE Duck plague is a disease with high morbidity and mortality rates, and it causes great losses for the duck breeding industry. 37378543 12 57 theme Duck 1534:1537 arg1 plague 1539:1544 Duck plague 1534:1544 IMPORTANCE Duck plague 1523:1544 IMPORTANCE Duck plague is a disease with high morbidity and mortality rates, and it causes great losses for the duck breeding industry. 37378543 14 58 theme immune 1903:1908 arg1 evasion 1910:1916 immune evasion 1903:1916 immune evasion 1903:1916 pUL10 plays complex roles in viral fusion, assembly, cell-to-cell spread, and immune evasion, which are closely related to its protein characteristics and partners. 37378543 11 59 theme future 1443:1448 arg1 exploration 1450:1460 future exploration 1443:1460 future exploration of the effect of pUL10 glycosylation on virus proliferation 1443:1520 This study provides a basis for future exploration of the effect of pUL10 glycosylation on virus proliferation. 37378543 15 60 theme pUL10 2062:2066 arg1 partner 2051:2057 a partner 2049:2057 a partner of pUL10 2049:2066 In this study, we systematically explored whether pUL49.5 (a partner of pUL10) plays roles in the localization, modification, and expression of pUL10. 37378543 10 61 link N-linked 1357:1364 arg1 glycosylation 1366:1378 the N-linked glycosylation 1353:1378 the N-linked glycosylation of DPV pUL10 during infection 1353:1408 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 11 62 theme pUL10 1479:1483 arg1 glycosylation 1485:1497 pUL10 glycosylation 1479:1497 pUL10 glycosylation 1479:1497 This study provides a basis for future exploration of the effect of pUL10 glycosylation on virus proliferation. 37378543 11 63 from proliferation 1508:1520 arg1 exploration 1450:1460 future exploration 1443:1460 future exploration of the effect of pUL10 glycosylation on virus proliferation 1443:1520 This study provides a basis for future exploration of the effect of pUL10 glycosylation on virus proliferation. 37378543 12 64 theme duck 1635:1638 arg1 industry 1649:1656 the duck breeding industry 1631:1656 the duck breeding industry 1631:1656 IMPORTANCE Duck plague is a disease with high morbidity and mortality rates, and it causes great losses for the duck breeding industry. 37378543 13 65 theme plague 1664:1669 arg1 agent 1700:1704 the causative agent 1686:1704 the causative agent of duck plague 1686:1719 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 65 theme plague 1664:1669 arg1 DPV 1678:1680 DPV 1678:1680 DPV 1678:1680 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 65 theme plague 1664:1669 arg1 virus 1671:1675 Duck plague virus 1659:1675 Duck plague virus (DPV) 1659:1681 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 10 66 theme molecular 1229:1237 arg1 mass 1239:1242 the molecular mass 1225:1242 the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection 1225:1408 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 8 67 theme N-terminal 995:1004 arg1 domains 1006:1012 the pUL49.5 N-terminal domains 983:1012 the pUL49.5 N-terminal domains 983:1012 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 11 68 from effect 1469:1474 arg1 proliferation 1508:1520 virus proliferation 1502:1520 virus proliferation 1502:1520 This study provides a basis for future exploration of the effect of pUL10 glycosylation on virus proliferation. 37378543 13 69 theme duck 1709:1712 arg1 plague 1714:1719 duck plague 1709:1719 duck plague 1709:1719 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 5 70 theme other 672:676 arg1 proteins 684:691 other viral proteins 672:691 other viral proteins that participate in pUL10 modification and localization 672:747 The characteristic differences in pUL10 in transfection and infection suggest that there are other viral proteins that participate in pUL10 modification and localization. 37378543 12 71 theme great 1614:1618 arg1 losses 1620:1625 great losses 1614:1625 great losses for the duck breeding industry 1614:1656 IMPORTANCE Duck plague is a disease with high morbidity and mortality rates, and it causes great losses for the duck breeding industry. 37378543 13 72 theme M 1780:1780 arg1 agent 1700:1704 the causative agent 1686:1704 the causative agent of duck plague 1686:1719 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 72 theme M 1780:1780 arg1 homolog 1756:1762 a homolog 1754:1762 a homolog 1754:1762 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 72 theme M 1780:1780 arg1 virus 1671:1675 Duck plague virus 1659:1675 Duck plague virus (DPV) 1659:1681 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 13 72 theme M 1780:1780 arg1 protein 1735:1741 DPV UL10 protein 1726:1741 DPV UL10 protein (pUL10) 1726:1749 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 14 73 theme cell-to-cell 1878:1889 arg1 spread 1891:1896 cell-to-cell spread 1878:1896 cell-to-cell spread 1878:1896 pUL10 plays complex roles in viral fusion, assembly, cell-to-cell spread, and immune evasion, which are closely related to its protein characteristics and partners. 37378543 14 74 theme protein 1952:1958 arg1 characteristics 1960:1974 its protein characteristics 1948:1974 its protein characteristics 1948:1974 pUL10 plays complex roles in viral fusion, assembly, cell-to-cell spread, and immune evasion, which are closely related to its protein characteristics and partners. 37378543 2 75 theme immune 310:315 arg1 evasion 317:323 immune evasion 310:323 immune evasion 310:323 pUL10 plays complex roles in viral fusion, assembly, cell-to-cell spread, and immune evasion, which are closely related to its protein characteristics and partners. 37378543 15 76 theme pUL10 2134:2138 arg1 modification 2102:2113 modification 2102:2113 modification 2102:2113 In this study, we systematically explored whether pUL49.5 (a partner of pUL10) plays roles in the localization, modification, and expression of pUL10. 37378543 15 76 theme pUL10 2134:2138 arg1 expression 2120:2129 expression 2120:2129 expression 2120:2129 In this study, we systematically explored whether pUL49.5 (a partner of pUL10) plays roles in the localization, modification, and expression of pUL10. 37378543 15 76 theme pUL10 2134:2138 arg1 localization 2088:2099 localization 2088:2099 localization 2088:2099 In this study, we systematically explored whether pUL49.5 (a partner of pUL10) plays roles in the localization, modification, and expression of pUL10. 37378543 13 77 gly glycoprotein 1767:1778 arg1 glycoprotein 1767:1778 glycoprotein M 1767:1780 glycoprotein M (gM) 1767:1785 Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL10 protein (pUL10) is a homolog of glycoprotein M (gM), which is conserved in herpesviruses. 37378543 1 78 theme plague 91:96 arg1 member 115:120 a member 113:120 a member of the alphaherpesvirus subfamily 113:154 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 78 theme plague 91:96 arg1 DPV 105:107 DPV 105:107 DPV 105:107 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 78 theme plague 91:96 arg1 virus 98:102 Duck plague virus 86:102 Duck plague virus (DPV) 86:108 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 5 79 theme pUL10 713:717 arg1 modification 719:730 pUL10 modification 713:730 pUL10 modification 713:730 The characteristic differences in pUL10 in transfection and infection suggest that there are other viral proteins that participate in pUL10 modification and localization. 37378543 8 80 theme disulfide 1052:1060 arg1 bond 1062:1065 a covalent disulfide bond 1041:1065 a covalent disulfide bond between two conserved cysteines 1041:1097 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 9 81 dep expression 1123:1132 arg1 modification 1168:1179 modification 1168:1179 modification 1168:1179 pUL49.5 promoted pUL10 expression and mature N-linked glycosylation modification. 37378543 10 82 gly glycosylation 1366:1378 arg1 pUL10 1387:1391 DPV pUL10 1383:1391 DPV pUL10 1383:1391 Moreover, deletion of UL49.5 in DPV caused the molecular mass of pUL10 to decrease by approximately3 to 10 kDa, which suggested that pUL49.5 was the main factor affecting the N-linked glycosylation of DPV pUL10 during infection. 37378543 0 83 theme Virus 53:57 arg1 Expression 27:36 Expression 27:36 Expression 27:36 N-Linked Glycosylation and Expression of Duck Plague Virus pUL10 Promoted by pUL49.5. 37378543 0 83 theme Virus 53:57 arg1 Glycosylation 9:21 N-Linked Glycosylation 0:21 N-Linked Glycosylation 0:21 N-Linked Glycosylation and Expression of Duck Plague Virus pUL10 Promoted by pUL49.5. 37378543 5 84 from differences 598:608 arg1 infection 639:647 infection 639:647 infection 639:647 The characteristic differences in pUL10 in transfection and infection suggest that there are other viral proteins that participate in pUL10 modification and localization. 37378543 5 84 from differences 598:608 arg1 transfection 622:633 transfection 622:633 transfection 622:633 The characteristic differences in pUL10 in transfection and infection suggest that there are other viral proteins that participate in pUL10 modification and localization. 37378543 5 84 from differences 598:608 arg1 pUL10 613:617 pUL10 613:617 pUL10 613:617 The characteristic differences in pUL10 in transfection and infection suggest that there are other viral proteins that participate in pUL10 modification and localization. 37378543 8 85 theme conserved 1079:1087 arg1 cysteines 1089:1097 two conserved cysteines 1075:1097 two conserved cysteines 1075:1097 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 6 86 theme interaction 774:784 arg1 partner 786:792 the interaction partner 770:792 the interaction partner of pUL10 770:801 Therefore, pUL49.5, the interaction partner of pUL10, was explored. 37378543 6 86 theme interaction 774:784 arg1 pUL49.5 761:767 pUL49.5 761:767 pUL49.5 761:767 Therefore, pUL49.5, the interaction partner of pUL10, was explored. 37378543 14 87 theme complex 1837:1843 arg1 roles 1845:1849 complex roles 1837:1849 complex roles 1837:1849 pUL10 plays complex roles in viral fusion, assembly, cell-to-cell spread, and immune evasion, which are closely related to its protein characteristics and partners. 37378543 9 88 theme pUL10 1117:1121 arg1 expression 1123:1132 pUL10 expression 1117:1132 pUL10 expression 1117:1132 pUL49.5 promoted pUL10 expression and mature N-linked glycosylation modification. 37378543 1 89 theme envelope 192:199 arg1 protein 201:207 a conserved envelope protein 180:207 a conserved envelope protein 180:207 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 89 theme envelope 192:199 arg1 UL10 218:221 protein UL10 210:221 protein UL10 (pUL10) 210:229 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 1 89 theme envelope 192:199 arg1 genome 165:170 its genome 161:170 its genome 161:170 Duck plague virus (DPV) is a member of the alphaherpesvirus subfamily, and its genome encodes a conserved envelope protein, protein UL10 (pUL10). 37378543 8 90 from forces 973:978 arg1 domains 1006:1012 the pUL49.5 N-terminal domains 983:1012 the pUL49.5 N-terminal domains 983:1012 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 8 90 from forces 973:978 arg1 domains 1029:1035 C-terminal domains 1018:1035 C-terminal domains 1018:1035 Their interaction entailed multiple interaction sites, including noncovalent forces in the pUL49.5 N-terminal domains and C-terminal domains and a covalent disulfide bond between two conserved cysteines. 37378543 4 91 theme glycosylation 522:534 arg1 modification 536:547 glycosylation modification 522:547 glycosylation modification 522:547 In this study, we identified the characteristics of pUL10, such as the type of glycosylation modification and subcellular localization. 35155371 6 0 theme excellent 939:947 arg1 properties 976:985 their excellent (bio)physical and chemical properties 933:985 their excellent (bio)physical and chemical properties 933:985 Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. 35155371 7 1 theme fucoidan 1088:1095 arg1 blend 1043:1047 a blend 1041:1047 a blend 1041:1047 Herein, we developed a microneedle array patch using a blend of kangfuxin (KFX), chitosan (CS), and fucoidan (FD), named KCFMN, for accelerating full-thickness wound healing. 35155371 8 2 theme effective 1246:1254 arg1 bio-functions 1256:1268 effective bio-functions 1246:1268 effective bio-functions 1246:1268 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. 35155371 9 3 dep physicochemical 1335:1349 arg1 macro-/micro-morphology 1302:1324 macro-/micro-morphology 1302:1324 macro-/micro-morphology 1302:1324 The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles were also studied. 35155371 1 4 theme stratum 261:267 arg1 corneum 269:275 the stratum corneum 257:275 the stratum corneum 257:275 Skin wound caused by external injury is usually difficult to be cured by conventional topical administration because of its poor drug diffusion across the stratum corneum. 35155371 11 5 theme epithelial 1655:1664 arg1 thickness 1666:1674 the epithelial thickness 1651:1674 the epithelial thickness 1651:1674 In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. 35155371 8 6 theme Chinese 1179:1185 arg1 medicine 1187:1194 The traditional Chinese medicine 1163:1194 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) 1163:1240 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. 35155371 2 7 theme drug 360:363 arg1 delivery 365:372 transdermal drug delivery 348:372 transdermal drug delivery 348:372 It has been recognized that stratum corneum is the major obstacle for transdermal drug delivery. 35155371 12 8 theme great 1738:1742 arg1 prospects 1744:1752 great prospects 1738:1752 great prospects 1738:1752 Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing. 35155371 12 8 theme great 1738:1742 arg1 dressing 1759:1766 a dressing 1757:1766 a dressing for full-thickness wound healing 1757:1799 Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing. 35155371 10 9 theme good 1493:1496 arg1 cytocompatibility 1498:1514 good cytocompatibility 1493:1514 good cytocompatibility 1493:1514 We showed that the KCFMN patch displayed noticeable antibacterial properties and good cytocompatibility. 35155371 3 10 theme epidermis 527:535 arg1 layers 552:557 the epidermis and the dermis layers 523:557 the epidermis and the dermis layers 523:557 To address this issue, microneedles (MNs) have been developed to penetrate the stratum corneum of the skin and then form micron-sized pores between the epidermis and the dermis layers. 35155371 3 11 theme dermis 545:550 arg1 layers 552:557 the epidermis and the dermis layers 523:557 the epidermis and the dermis layers 523:557 To address this issue, microneedles (MNs) have been developed to penetrate the stratum corneum of the skin and then form micron-sized pores between the epidermis and the dermis layers. 35155371 4 12 theme biomacromolecule 569:584 arg1 molecules 614:622 insoluble drug molecules 599:622 insoluble drug molecules 599:622 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 35155371 4 12 theme biomacromolecule 569:584 arg1 such 563:566 such 563:566 such 563:566 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 35155371 4 12 theme biomacromolecule 569:584 arg1 drugs 586:590 biomacromolecule drugs 569:590 biomacromolecule drugs 569:590 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 35155371 5 13 theme wound 735:739 arg1 infection 741:749 wound infection 735:749 wound infection 735:749 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. 35155371 6 14 theme due 926:928 arg1 applications 913:924 multifarious biomedical applications 889:924 multifarious biomedical applications due to their excellent (bio)physical and chemical properties 889:985 Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. 35155371 12 15 theme wound 1787:1791 arg1 healing 1793:1799 full-thickness wound healing 1772:1799 full-thickness wound healing 1772:1799 Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing. 35155371 6 16 dep excellent 939:947 arg1 bio 950:952 bio 950:952 bio 950:952 Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. 35155371 7 17 theme full-thickness 1133:1146 arg1 healing 1154:1160 full-thickness wound healing 1133:1160 full-thickness wound healing 1133:1160 Herein, we developed a microneedle array patch using a blend of kangfuxin (KFX), chitosan (CS), and fucoidan (FD), named KCFMN, for accelerating full-thickness wound healing. 35155371 1 18 theme external 127:134 arg1 injury 136:141 external injury 127:141 external injury 127:141 Skin wound caused by external injury is usually difficult to be cured by conventional topical administration because of its poor drug diffusion across the stratum corneum. 35155371 10 19 theme noticeable 1453:1462 arg1 properties 1478:1487 noticeable antibacterial properties 1453:1487 noticeable antibacterial properties 1453:1487 We showed that the KCFMN patch displayed noticeable antibacterial properties and good cytocompatibility. 35155371 11 20 from development 1592:1602 arg1 wound 1624:1628 a full-thickness wound 1607:1628 a full-thickness wound 1607:1628 In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. 35155371 11 20 from development 1592:1602 arg1 rats 1633:1636 rats 1633:1636 rats 1633:1636 In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. 35155371 8 21 theme Periplaneta 1215:1225 arg1 PA 1238:1239 PA 1238:1239 PA 1238:1239 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. 35155371 8 21 theme Periplaneta 1215:1225 arg1 americana 1227:1235 Periplaneta americana 1215:1235 Periplaneta americana (PA) 1215:1240 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. 35155371 4 22 theme effective 643:651 arg1 penetration 665:675 effective transdermal penetration 643:675 effective transdermal penetration 643:675 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 35155371 7 23 theme wound 1148:1152 arg1 healing 1154:1160 full-thickness wound healing 1133:1160 full-thickness wound healing 1133:1160 Herein, we developed a microneedle array patch using a blend of kangfuxin (KFX), chitosan (CS), and fucoidan (FD), named KCFMN, for accelerating full-thickness wound healing. 35155371 6 24 theme biomedical 902:911 arg1 applications 913:924 multifarious biomedical applications 889:924 multifarious biomedical applications due to their excellent (bio)physical and chemical properties 889:985 Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. 35155371 5 25 theme important 784:792 arg1 value 794:798 important value 784:798 important value for wound healing 784:816 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. 35155371 3 26 theme skin 477:480 arg1 corneum 462:468 the stratum corneum 450:468 the stratum corneum of the skin 450:480 To address this issue, microneedles (MNs) have been developed to penetrate the stratum corneum of the skin and then form micron-sized pores between the epidermis and the dermis layers. 35155371 1 27 theme conventional 179:190 arg1 administration 200:213 conventional topical administration 179:213 conventional topical administration 179:213 Skin wound caused by external injury is usually difficult to be cured by conventional topical administration because of its poor drug diffusion across the stratum corneum. 35155371 0 28 theme Array 12:16 arg1 Patch 18:22 Microneedle Array Patch 0:22 Microneedle Array Patch Made of Kangfuxin/Chitosan/Fucoidan Complex 0:66 Microneedle Array Patch Made of Kangfuxin/Chitosan/Fucoidan Complex Enables Full-Thickness Wound Healing. 35155371 6 29 theme multifarious 889:900 arg1 applications 913:924 multifarious biomedical applications 889:924 multifarious biomedical applications due to their excellent (bio)physical and chemical properties 889:985 Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. 35155371 7 30 theme chitosan 1069:1076 arg1 blend 1043:1047 a blend 1041:1047 a blend 1041:1047 Herein, we developed a microneedle array patch using a blend of kangfuxin (KFX), chitosan (CS), and fucoidan (FD), named KCFMN, for accelerating full-thickness wound healing. 35155371 11 31 theme wound 1578:1582 arg1 healing 1584:1590 wound healing 1578:1590 the wound healing development in a full-thickness wound in rats 1574:1636 In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. 35155371 1 32 theme Skin 106:109 arg1 wound 111:115 Skin wound 106:115 Skin wound caused by external injury 106:141 Skin wound caused by external injury is usually difficult to be cured by conventional topical administration because of its poor drug diffusion across the stratum corneum. 35155371 1 33 theme topical 192:198 arg1 administration 200:213 conventional topical administration 179:213 conventional topical administration 179:213 Skin wound caused by external injury is usually difficult to be cured by conventional topical administration because of its poor drug diffusion across the stratum corneum. 35155371 0 34 theme Microneedle 0:10 arg1 Patch 18:22 Microneedle Array Patch 0:22 Microneedle Array Patch Made of Kangfuxin/Chitosan/Fucoidan Complex 0:66 Microneedle Array Patch Made of Kangfuxin/Chitosan/Fucoidan Complex Enables Full-Thickness Wound Healing. 35155371 10 35 theme KCFMN 1431:1435 arg1 patch 1437:1441 the KCFMN patch 1427:1441 the KCFMN patch 1427:1441 We showed that the KCFMN patch displayed noticeable antibacterial properties and good cytocompatibility. 35155371 11 36 theme collagen 1680:1687 arg1 deposition 1689:1698 collagen deposition 1680:1698 collagen deposition 1680:1698 In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. 35155371 4 37 theme transdermal 653:663 arg1 penetration 665:675 effective transdermal penetration 643:675 effective transdermal penetration 643:675 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 35155371 5 38 theme array 708:712 arg1 patch 714:718 A multifunctional microneedle array patch 678:718 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding 678:778 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. 35155371 12 39 theme full-thickness 1772:1785 arg1 healing 1793:1799 full-thickness wound healing 1772:1799 full-thickness wound healing 1772:1799 Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing. 35155371 8 40 theme traditional 1167:1177 arg1 medicine 1187:1194 The traditional Chinese medicine 1163:1194 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) 1163:1240 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. 35155371 11 41 theme KCFMN 1536:1540 arg1 patch 1542:1546 the KCFMN patch 1532:1546 the KCFMN patch 1532:1546 In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. 35155371 3 42 theme stratum 454:460 arg1 corneum 462:468 the stratum corneum 450:468 the stratum corneum of the skin 450:480 To address this issue, microneedles (MNs) have been developed to penetrate the stratum corneum of the skin and then form micron-sized pores between the epidermis and the dermis layers. 35155371 11 43 theme healing 1584:1590 arg1 development 1592:1602 the wound healing development 1574:1602 the wound healing development in a full-thickness wound in rats 1574:1636 In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. 35155371 2 44 theme stratum 306:312 arg1 corneum 314:320 stratum corneum 306:320 stratum corneum 306:320 It has been recognized that stratum corneum is the major obstacle for transdermal drug delivery. 35155371 2 44 theme stratum 306:312 arg1 obstacle 335:342 the major obstacle 325:342 the major obstacle for transdermal drug delivery 325:372 It has been recognized that stratum corneum is the major obstacle for transdermal drug delivery. 35155371 8 45 theme wound 1283:1287 arg1 healing 1289:1295 wound healing 1283:1295 wound healing 1283:1295 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. 35155371 0 46 theme Kangfuxin/Chitosan/Fucoidan 32:58 arg1 Complex 60:66 Kangfuxin/Chitosan/Fucoidan Complex 32:66 Kangfuxin/Chitosan/Fucoidan Complex 32:66 Microneedle Array Patch Made of Kangfuxin/Chitosan/Fucoidan Complex Enables Full-Thickness Wound Healing. 35155371 6 47 theme chemical 967:974 arg1 properties 976:985 their excellent (bio)physical and chemical properties 933:985 their excellent (bio)physical and chemical properties 933:985 Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. 35155371 9 48 theme bio 1331:1333 arg1 properties 1351:1360 The macro-/micro-morphology and (bio)physicochemical properties 1298:1360 The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles 1298:1391 The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles were also studied. 35155371 10 49 theme antibacterial 1464:1476 arg1 properties 1478:1487 noticeable antibacterial properties 1453:1487 noticeable antibacterial properties 1453:1487 We showed that the KCFMN patch displayed noticeable antibacterial properties and good cytocompatibility. 35155371 6 50 theme much 871:874 arg1 attention 876:884 much attention 871:884 much attention 871:884 Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. 35155371 9 51 theme composite 1370:1378 arg1 microneedles 1380:1391 such composite microneedles 1365:1391 such composite microneedles 1365:1391 The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles were also studied. 35155371 1 52 theme poor 230:233 arg1 diffusion 240:248 its poor drug diffusion 226:248 its poor drug diffusion across the stratum corneum 226:275 Skin wound caused by external injury is usually difficult to be cured by conventional topical administration because of its poor drug diffusion across the stratum corneum. 35155371 6 53 theme physical 954:961 arg1 properties 976:985 their excellent (bio)physical and chemical properties 933:985 their excellent (bio)physical and chemical properties 933:985 Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. 35155371 5 54 theme tissue 763:768 arg1 remolding 770:778 tissue remolding 763:778 tissue remolding 763:778 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. 35155371 8 55 contain has 1242:1244 arg2 bio-functions 1256:1268 effective bio-functions 1246:1268 effective bio-functions 1246:1268 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. 35155371 8 55 contain has 1242:1244 arg1 medicine 1187:1194 The traditional Chinese medicine 1163:1194 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) 1163:1240 The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. 35155371 2 56 theme transdermal 348:358 arg1 delivery 365:372 transdermal drug delivery 348:372 transdermal drug delivery 348:372 It has been recognized that stratum corneum is the major obstacle for transdermal drug delivery. 35155371 5 57 theme wound 804:808 arg1 healing 810:816 wound healing 804:816 wound healing 804:816 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. 35155371 9 58 theme physicochemical 1335:1349 arg1 properties 1351:1360 The macro-/micro-morphology and (bio)physicochemical properties 1298:1360 The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles 1298:1391 The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles were also studied. 35155371 7 59 theme kangfuxin 1052:1060 arg1 blend 1043:1047 a blend 1041:1047 a blend 1041:1047 Herein, we developed a microneedle array patch using a blend of kangfuxin (KFX), chitosan (CS), and fucoidan (FD), named KCFMN, for accelerating full-thickness wound healing. 35155371 7 60 theme microneedle 1011:1021 arg1 patch 1029:1033 a microneedle array patch 1009:1033 a microneedle array patch 1009:1033 Herein, we developed a microneedle array patch using a blend of kangfuxin (KFX), chitosan (CS), and fucoidan (FD), named KCFMN, for accelerating full-thickness wound healing. 35155371 12 61 theme KCFMN 1722:1726 arg1 patch 1728:1732 this versatile KCFMN patch 1707:1732 this versatile KCFMN patch 1707:1732 Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing. 35155371 5 62 theme multifunctional 680:694 arg1 patch 714:718 A multifunctional microneedle array patch 678:718 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding 678:778 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. 35155371 12 63 contain has 1734:1736 arg1 patch 1728:1732 this versatile KCFMN patch 1707:1732 this versatile KCFMN patch 1707:1732 Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing. 35155371 12 63 contain has 1734:1736 arg2 dressing 1759:1766 a dressing 1757:1766 a dressing for full-thickness wound healing 1757:1799 Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing. 35155371 12 63 contain has 1734:1736 arg2 prospects 1744:1752 great prospects 1738:1752 great prospects 1738:1752 Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing. 35155371 7 64 theme array 1023:1027 arg1 patch 1029:1033 a microneedle array patch 1009:1033 a microneedle array patch 1009:1033 Herein, we developed a microneedle array patch using a blend of kangfuxin (KFX), chitosan (CS), and fucoidan (FD), named KCFMN, for accelerating full-thickness wound healing. 35155371 12 65 theme versatile 1712:1720 arg1 patch 1728:1732 this versatile KCFMN patch 1707:1732 this versatile KCFMN patch 1707:1732 Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing. 35155371 1 66 theme drug 235:238 arg1 diffusion 240:248 its poor drug diffusion 226:248 its poor drug diffusion across the stratum corneum 226:275 Skin wound caused by external injury is usually difficult to be cured by conventional topical administration because of its poor drug diffusion across the stratum corneum. 35155371 5 67 theme microneedle 696:706 arg1 patch 714:718 A multifunctional microneedle array patch 678:718 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding 678:778 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. 35155371 6 68 theme marine 833:838 arg1 polysaccharides 840:854 marine polysaccharides 833:854 marine polysaccharides 833:854 Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. 35155371 2 69 theme major 329:333 arg1 corneum 314:320 stratum corneum 306:320 stratum corneum 306:320 It has been recognized that stratum corneum is the major obstacle for transdermal drug delivery. 35155371 2 69 theme major 329:333 arg1 obstacle 335:342 the major obstacle 325:342 the major obstacle for transdermal drug delivery 325:372 It has been recognized that stratum corneum is the major obstacle for transdermal drug delivery. 35155371 9 70 theme such 1365:1368 arg1 microneedles 1380:1391 such composite microneedles 1365:1391 such composite microneedles 1365:1391 The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles were also studied. 35155371 0 71 theme Wound 91:95 arg1 Healing 97:103 Full-Thickness Wound Healing 76:103 Full-Thickness Wound Healing 76:103 Microneedle Array Patch Made of Kangfuxin/Chitosan/Fucoidan Complex Enables Full-Thickness Wound Healing. 35155371 3 72 theme micron-sized 496:507 arg1 pores 509:513 micron-sized pores 496:513 micron-sized pores between the epidermis and the dermis layers 496:557 To address this issue, microneedles (MNs) have been developed to penetrate the stratum corneum of the skin and then form micron-sized pores between the epidermis and the dermis layers. 35155371 4 73 theme drug 609:612 arg1 molecules 614:622 insoluble drug molecules 599:622 insoluble drug molecules 599:622 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 35155371 4 73 theme drug 609:612 arg1 such 563:566 such 563:566 such 563:566 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 35155371 4 73 theme drug 609:612 arg1 drugs 586:590 biomacromolecule drugs 569:590 biomacromolecule drugs 569:590 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 35155371 0 74 theme Full-Thickness 76:89 arg1 Healing 97:103 Full-Thickness Wound Healing 76:103 Full-Thickness Wound Healing 76:103 Microneedle Array Patch Made of Kangfuxin/Chitosan/Fucoidan Complex Enables Full-Thickness Wound Healing. 35155371 5 75 contain has 780:782 arg1 patch 714:718 A multifunctional microneedle array patch 678:718 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding 678:778 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. 35155371 5 75 contain has 780:782 arg2 value 794:798 important value 784:798 important value for wound healing 784:816 A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. 35155371 9 76 theme microneedles 1380:1391 arg1 properties 1351:1360 The macro-/micro-morphology and (bio)physicochemical properties 1298:1360 The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles 1298:1391 The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles were also studied. 35155371 11 77 theme full-thickness 1609:1622 arg1 wound 1624:1628 a full-thickness wound 1607:1628 a full-thickness wound 1607:1628 In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. 35155371 4 78 theme insoluble 599:607 arg1 molecules 614:622 insoluble drug molecules 599:622 insoluble drug molecules 599:622 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 35155371 4 78 theme insoluble 599:607 arg1 such 563:566 such 563:566 such 563:566 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 35155371 4 78 theme insoluble 599:607 arg1 drugs 586:590 biomacromolecule drugs 569:590 biomacromolecule drugs 569:590 As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. 36361582 7 0 theme N120Q 1132:1136 arg1 levels 1118:1123 The expression levels 1103:1123 The expression levels of the N120Q and N272Q mutants 1103:1154 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 7 0 theme N120Q 1132:1136 arg1 FSHG-wt 1196:1202 the FSHG-wt 1192:1202 the FSHG-wt 1192:1202 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 7 0 theme N120Q 1132:1136 arg1 % 1179:1179 % 1179:1179 % 1179:1179 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 2 1 theme adenosine 366:374 arg1 monophosphate 376:388 cyclic adenosine monophosphate 359:388 cyclic adenosine monophosphate (cAMP) signal transduction 359:415 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 2 1 theme adenosine 366:374 arg1 cAMP 391:394 cAMP 391:394 cAMP 391:394 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 12 2 theme cell 1818:1821 arg1 receptors 1831:1839 cell surface receptors 1818:1839 cell surface receptors 1818:1839 This finding implies that the cAMP response, mediated by G proteins, is directly related to the loss of cell surface receptors as a result of high-agonist treatment. 36361582 6 3 theme negligible 1074:1083 arg1 level 1096:1100 a negligible expression level 1072:1100 a negligible expression level 1072:1100 The expression level of the N191Q mutant was only 9.2% relative to that of the eel FSHR-wt, indicating a negligible expression level. 36361582 2 4 gly glycosylated 310:321 arg1 sites 323:327 conserved glycosylated sites 300:327 conserved glycosylated sites in eel FSHR 300:339 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 2 5 theme conserved 300:308 arg1 sites 323:327 conserved glycosylated sites 300:327 conserved glycosylated sites in eel FSHR 300:339 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 12 6 theme receptors 1831:1839 arg1 loss 1810:1813 the loss 1806:1813 the loss of cell surface receptors 1806:1839 This finding implies that the cAMP response, mediated by G proteins, is directly related to the loss of cell surface receptors as a result of high-agonist treatment. 36361582 3 7 theme glycosylation 526:538 arg1 sites 540:544 the N-linked glycosylation sites 513:544 the N-linked glycosylation sites of eel FSHR 513:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 3 7 theme glycosylation 526:538 arg1 FSHR 553:556 eel FSHR 549:556 eel FSHR 549:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 1 8 theme several 182:188 arg1 sites 213:217 several N-linked glycosylation sites 182:217 several N-linked glycosylation sites in its extracellular region 182:245 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 2 9 theme eel 332:334 arg1 FSHR 336:339 eel FSHR 332:339 eel FSHR 332:339 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 1 10 theme glycosylation 199:211 arg1 sites 213:217 several N-linked glycosylation sites 182:217 several N-linked glycosylation sites in its extracellular region 182:245 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 4 11 theme cAMP 595:598 arg1 response 600:607 the cAMP response 591:607 the cAMP response 591:607 In the eel FSHR wild-type (wt), the cAMP response was gradually increased in a dose-dependent manner (0.01-1500 ng/mL), displaying a high response (approximately 57.5 nM/104 cells) at the Rmax level. 36361582 4 12 dep wild-type 575:583 arg1 wt 586:587 wt 586:587 wt 586:587 In the eel FSHR wild-type (wt), the cAMP response was gradually increased in a dose-dependent manner (0.01-1500 ng/mL), displaying a high response (approximately 57.5 nM/104 cells) at the Rmax level. 36361582 3 13 theme FSHR 553:556 arg1 sites 540:544 the N-linked glycosylation sites 513:544 the N-linked glycosylation sites of eel FSHR 513:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 3 13 theme FSHR 553:556 arg1 FSHR 553:556 eel FSHR 549:556 eel FSHR 549:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 0 14 from Transduction 65:76 arg1 Receptor 114:121 Eel Follicle-Stimulating Hormone Receptor 81:121 Eel Follicle-Stimulating Hormone Receptor 81:121 The N-Linked Glycosylation Site N191 Is Necessary for PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor. 36361582 1 15 theme extracellular 226:238 arg1 region 240:245 its extracellular region 222:245 its extracellular region 222:245 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 1 16 from sites 213:217 arg1 region 240:245 its extracellular region 222:245 its extracellular region 222:245 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 8 17 theme cAMP 1324:1327 arg1 responsiveness 1329:1342 the mostly impaired cAMP responsiveness 1304:1342 the mostly impaired cAMP responsiveness 1304:1342 The N288Q mutant had an expression level similar to that of the eel FSHR-wt, despite the mostly impaired cAMP responsiveness. 36361582 5 18 theme high-ligand 866:876 arg1 treatment 878:886 high-ligand treatment 866:886 high-ligand treatment 866:886 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 9 19 theme cell 1361:1364 arg1 complexes 1391:1399 the cell surface agonist-receptor complexes 1357:1399 the cell surface agonist-receptor complexes 1357:1399 The loss of the cell surface agonist-receptor complexes was very rapid in the cells expressing eel FSHR-wt and FSHR-N288Q mutants. 36361582 9 20 from cells 1423:1427 arg1 loss 1349:1352 The loss 1345:1352 The loss of the cell surface agonist-receptor complexes 1345:1399 The loss of the cell surface agonist-receptor complexes was very rapid in the cells expressing eel FSHR-wt and FSHR-N288Q mutants. 36361582 9 20 from cells 1423:1427 arg1 rapid 1410:1414 rapid 1410:1414 rapid 1410:1414 The loss of the cell surface agonist-receptor complexes was very rapid in the cells expressing eel FSHR-wt and FSHR-N288Q mutants. 36361582 12 21 theme treatment 1869:1877 arg1 result 1846:1851 a result 1844:1851 a result of high-agonist treatment 1844:1877 This finding implies that the cAMP response, mediated by G proteins, is directly related to the loss of cell surface receptors as a result of high-agonist treatment. 36361582 0 22 theme PKA 54:56 arg1 Transduction 65:76 PKA Signal Transduction 54:76 PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor 54:121 The N-Linked Glycosylation Site N191 Is Necessary for PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor. 36361582 9 23 theme agonist-receptor 1374:1389 arg1 complexes 1391:1399 the cell surface agonist-receptor complexes 1357:1399 the cell surface agonist-receptor complexes 1357:1399 The loss of the cell surface agonist-receptor complexes was very rapid in the cells expressing eel FSHR-wt and FSHR-N288Q mutants. 36361582 8 24 contain had 1236:1238 arg2 level 1254:1258 an expression level 1240:1258 an expression level similar to that of the eel FSHR-wt 1240:1293 The N288Q mutant had an expression level similar to that of the eel FSHR-wt, despite the mostly impaired cAMP responsiveness. 36361582 8 24 contain had 1236:1238 arg1 mutant 1229:1234 The N288Q mutant 1219:1234 The N288Q mutant 1219:1234 The N288Q mutant had an expression level similar to that of the eel FSHR-wt, despite the mostly impaired cAMP responsiveness. 36361582 3 25 gly glycosylation 526:538 arg1 FSHR 553:556 eel FSHR 549:556 eel FSHR 549:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 3 25 gly glycosylation 526:538 arg2 FSHR 553:556 eel FSHR 549:556 eel FSHR 549:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 3 25 gly glycosylation 526:538 arg2 sites 540:544 the N-linked glycosylation sites 513:544 the N-linked glycosylation sites of eel FSHR 513:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 5 26 theme decreased 821:829 arg1 transduction 838:849 a considerably decreased signal transduction 806:849 a considerably decreased signal transduction 806:849 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 5 26 theme decreased 821:829 arg1 result 856:861 a result 854:861 a result of high-ligand treatment 854:886 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 3 27 link N-linked 517:524 arg1 sites 540:544 the N-linked glycosylation sites 513:544 the N-linked glycosylation sites of eel FSHR 513:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 3 27 link N-linked 517:524 arg1 FSHR 553:556 eel FSHR 549:556 eel FSHR 549:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 0 28 theme Eel 81:83 arg1 Receptor 114:121 Eel Follicle-Stimulating Hormone Receptor 81:121 Eel Follicle-Stimulating Hormone Receptor 81:121 The N-Linked Glycosylation Site N191 Is Necessary for PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor. 36361582 1 29 theme hormone 149:155 arg1 FSHR 167:170 FSHR 167:170 FSHR 167:170 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 1 29 theme hormone 149:155 arg1 receptor 157:164 The follicle-stimulating hormone receptor 124:164 The follicle-stimulating hormone receptor (FSHR) 124:171 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 1 30 link N-linked 190:197 arg1 sites 213:217 several N-linked glycosylation sites 182:217 several N-linked glycosylation sites in its extracellular region 182:245 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 0 31 theme Hormone 106:112 arg1 Receptor 114:121 Eel Follicle-Stimulating Hormone Receptor 81:121 Eel Follicle-Stimulating Hormone Receptor 81:121 The N-Linked Glycosylation Site N191 Is Necessary for PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor. 36361582 7 32 dep % 1179:1179 arg1 35.9 1175:1178 35.9 1175:1178 35.9 1175:1178 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 4 33 theme high 692:695 arg1 response 697:704 a high response 690:704 a high response (approximately 57.5 nM/104 cells) 690:738 In the eel FSHR wild-type (wt), the cAMP response was gradually increased in a dose-dependent manner (0.01-1500 ng/mL), displaying a high response (approximately 57.5 nM/104 cells) at the Rmax level. 36361582 4 33 theme high 692:695 arg1 cells 733:737 approximately 57.5 nM/104 cells 707:737 approximately 57.5 nM/104 cells 707:737 In the eel FSHR wild-type (wt), the cAMP response was gradually increased in a dose-dependent manner (0.01-1500 ng/mL), displaying a high response (approximately 57.5 nM/104 cells) at the Rmax level. 36361582 2 34 theme signal 397:402 arg1 transduction 404:415 cyclic adenosine monophosphate (cAMP) signal transduction 359:415 cyclic adenosine monophosphate (cAMP) signal transduction 359:415 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 12 35 theme cAMP 1744:1747 arg1 response 1749:1756 the cAMP response 1740:1756 the cAMP response 1740:1756 This finding implies that the cAMP response, mediated by G proteins, is directly related to the loss of cell surface receptors as a result of high-agonist treatment. 36361582 12 35 theme cAMP 1744:1747 arg1 related 1795:1801 related 1795:1801 related 1795:1801 This finding implies that the cAMP response, mediated by G proteins, is directly related to the loss of cell surface receptors as a result of high-agonist treatment. 36361582 7 36 theme FSHG-wt 1196:1202 arg1 % 1187:1187 24% 1185:1187 24% of the FSHG-wt 1185:1202 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 7 36 theme FSHG-wt 1196:1202 arg1 FSHG-wt 1196:1202 the FSHG-wt 1192:1202 the FSHG-wt 1192:1202 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 7 36 theme FSHG-wt 1196:1202 arg1 levels 1118:1123 The expression levels 1103:1123 The expression levels of the N120Q and N272Q mutants 1103:1154 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 7 36 theme FSHG-wt 1196:1202 arg1 % 1179:1179 % 1179:1179 % 1179:1179 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 0 37 theme Glycosylation 13:25 arg1 Site 27:30 The N-Linked Glycosylation Site N191 0:35 The N-Linked Glycosylation Site N191 0:35 The N-Linked Glycosylation Site N191 Is Necessary for PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor. 36361582 0 37 theme Glycosylation 13:25 arg1 Necessary 40:48 Necessary 40:48 Necessary 40:48 The N-Linked Glycosylation Site N191 Is Necessary for PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor. 36361582 5 38 theme treatment 878:886 arg1 transduction 838:849 a considerably decreased signal transduction 806:849 a considerably decreased signal transduction 806:849 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 5 38 theme treatment 878:886 arg1 result 856:861 a result 854:861 a result of high-ligand treatment 854:886 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 3 39 theme site-directed 426:438 arg1 mutagenesis 440:450 site-directed mutagenesis 426:450 site-directed mutagenesis 426:450 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 9 40 theme FSHR-N288Q 1456:1465 arg1 mutants 1467:1473 FSHR-N288Q mutants 1456:1473 FSHR-N288Q mutants 1456:1473 The loss of the cell surface agonist-receptor complexes was very rapid in the cells expressing eel FSHR-wt and FSHR-N288Q mutants. 36361582 1 41 contain contains 173:180 arg1 FSHR 167:170 FSHR 167:170 FSHR 167:170 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 1 41 contain contains 173:180 arg2 sites 213:217 several N-linked glycosylation sites 182:217 several N-linked glycosylation sites in its extracellular region 182:245 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 1 41 contain contains 173:180 arg1 receptor 157:164 The follicle-stimulating hormone receptor 124:164 The follicle-stimulating hormone receptor (FSHR) 124:171 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 2 42 theme cyclic 359:364 arg1 monophosphate 376:388 cyclic adenosine monophosphate 359:388 cyclic adenosine monophosphate (cAMP) signal transduction 359:415 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 2 42 theme cyclic 359:364 arg1 cAMP 391:394 cAMP 391:394 cAMP 391:394 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 10 43 with treatment 1578:1586 arg1 concentration 1600:1612 a high concentration 1593:1612 a high concentration of the agonist 1593:1627 Specifically, the N191Q mutant was completely impaired by the loss of cell surface receptors, despite treatment with a high concentration of the agonist. 36361582 5 44 theme signal 948:953 arg1 transduction 955:966 a completely impaired signal transduction 926:966 a completely impaired signal transduction 926:966 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 8 45 theme eel 1283:1285 arg1 FSHR-wt 1287:1293 the eel FSHR-wt 1279:1293 the eel FSHR-wt 1279:1293 The N288Q mutant had an expression level similar to that of the eel FSHR-wt, despite the mostly impaired cAMP responsiveness. 36361582 10 46 theme surface 1551:1557 arg1 receptors 1559:1567 cell surface receptors 1546:1567 cell surface receptors 1546:1567 Specifically, the N191Q mutant was completely impaired by the loss of cell surface receptors, despite treatment with a high concentration of the agonist. 36361582 10 47 theme high 1595:1598 arg1 concentration 1600:1612 a high concentration 1593:1612 a high concentration of the agonist 1593:1627 Specifically, the N191Q mutant was completely impaired by the loss of cell surface receptors, despite treatment with a high concentration of the agonist. 36361582 12 48 theme high-agonist 1856:1867 arg1 treatment 1869:1877 high-agonist treatment 1856:1877 high-agonist treatment 1856:1877 This finding implies that the cAMP response, mediated by G proteins, is directly related to the loss of cell surface receptors as a result of high-agonist treatment. 36361582 4 49 theme Rmax 747:750 arg1 level 752:756 the Rmax level 743:756 the Rmax level 743:756 In the eel FSHR wild-type (wt), the cAMP response was gradually increased in a dose-dependent manner (0.01-1500 ng/mL), displaying a high response (approximately 57.5 nM/104 cells) at the Rmax level. 36361582 2 50 theme monophosphate 376:388 arg1 transduction 404:415 cyclic adenosine monophosphate (cAMP) signal transduction 359:415 cyclic adenosine monophosphate (cAMP) signal transduction 359:415 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 5 51 dep mutants 765:771 arg1 N272Q 781:785 N272Q 781:785 N272Q 781:785 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 5 51 dep mutants 765:771 arg1 N288Q 792:796 N288Q 792:796 N288Q 792:796 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 5 51 dep mutants 765:771 arg1 N120Q 774:778 N120Q 774:778 N120Q 774:778 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 5 51 dep mutants 765:771 arg1 mutants 765:771 Three mutants 759:771 Three mutants (N120Q, N272Q, and N288Q) 759:797 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 6 52 theme mutant 1003:1008 arg1 % 1022:1022 9.2% 1019:1022 9.2% relative to that of the eel FSHR-wt 1019:1058 The expression level of the N191Q mutant was only 9.2% relative to that of the eel FSHR-wt, indicating a negligible expression level. 36361582 6 52 theme mutant 1003:1008 arg1 level 984:988 The expression level 969:988 The expression level of the N191Q mutant 969:1008 The expression level of the N191Q mutant was only 9.2% relative to that of the eel FSHR-wt, indicating a negligible expression level. 36361582 1 53 gly glycosylation 199:211 arg2 sites 213:217 several N-linked glycosylation sites 182:217 several N-linked glycosylation sites in its extracellular region 182:245 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 2 54 theme glycosylated 310:321 arg1 sites 323:327 conserved glycosylated sites 300:327 conserved glycosylated sites in eel FSHR 300:339 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 11 55 theme signal 1693:1698 arg1 transduction 1700:1711 cAMP signal transduction 1688:1711 cAMP signal transduction 1688:1711 Therefore, we suggest that the N191 site is necessary for cAMP signal transduction. 36361582 3 56 theme N-linked 517:524 arg1 sites 540:544 the N-linked glycosylation sites 513:544 the N-linked glycosylation sites of eel FSHR 513:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 3 56 theme N-linked 517:524 arg1 FSHR 553:556 eel FSHR 549:556 eel FSHR 549:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 12 57 theme surface 1823:1829 arg1 receptors 1831:1839 cell surface receptors 1818:1839 cell surface receptors 1818:1839 This finding implies that the cAMP response, mediated by G proteins, is directly related to the loss of cell surface receptors as a result of high-agonist treatment. 36361582 1 58 theme N-linked 190:197 arg1 sites 213:217 several N-linked glycosylation sites 182:217 several N-linked glycosylation sites in its extracellular region 182:245 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 6 59 theme eel 1048:1050 arg1 FSHR-wt 1052:1058 the eel FSHR-wt 1044:1058 the eel FSHR-wt 1044:1058 The expression level of the N191Q mutant was only 9.2% relative to that of the eel FSHR-wt, indicating a negligible expression level. 36361582 3 60 dep mutations 467:475 arg1 mutations 467:475 four mutations 462:475 four mutations (N120Q, N191Q, N272Q, and N288Q) 462:508 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 3 60 dep mutations 467:475 arg1 N272Q 492:496 N272Q 492:496 N272Q 492:496 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 3 60 dep mutations 467:475 arg1 N288Q 503:507 N288Q 503:507 N288Q 503:507 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 3 60 dep mutations 467:475 arg1 N191Q 485:489 N191Q 485:489 N191Q 485:489 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 3 61 theme eel 549:551 arg1 FSHR 553:556 eel FSHR 549:556 eel FSHR 549:556 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 10 62 theme N191Q 1494:1498 arg1 mutant 1500:1505 the N191Q mutant 1490:1505 the N191Q mutant 1490:1505 Specifically, the N191Q mutant was completely impaired by the loss of cell surface receptors, despite treatment with a high concentration of the agonist. 36361582 8 63 theme impaired 1315:1322 arg1 responsiveness 1329:1342 the mostly impaired cAMP responsiveness 1304:1342 the mostly impaired cAMP responsiveness 1304:1342 The N288Q mutant had an expression level similar to that of the eel FSHR-wt, despite the mostly impaired cAMP responsiveness. 36361582 5 64 theme signal 831:836 arg1 transduction 838:849 a considerably decreased signal transduction 806:849 a considerably decreased signal transduction 806:849 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 5 64 theme signal 831:836 arg1 result 856:861 a result 854:861 a result of high-ligand treatment 854:886 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 1 65 theme follicle-stimulating 128:147 arg1 FSHR 167:170 FSHR 167:170 FSHR 167:170 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 1 65 theme follicle-stimulating 128:147 arg1 receptor 157:164 The follicle-stimulating hormone receptor 124:164 The follicle-stimulating hormone receptor (FSHR) 124:171 The follicle-stimulating hormone receptor (FSHR) contains several N-linked glycosylation sites in its extracellular region. 36361582 0 66 theme Signal 58:63 arg1 Transduction 65:76 PKA Signal Transduction 54:76 PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor 54:121 The N-Linked Glycosylation Site N191 Is Necessary for PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor. 36361582 9 67 from rapid 1410:1414 arg1 cells 1423:1427 the cells 1419:1427 the cells expressing eel FSHR-wt and FSHR-N288Q mutants 1419:1473 The loss of the cell surface agonist-receptor complexes was very rapid in the cells expressing eel FSHR-wt and FSHR-N288Q mutants. 36361582 2 68 theme present 265:271 arg1 study 273:277 the present study 261:277 the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction 261:415 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 9 69 theme surface 1366:1372 arg1 complexes 1391:1399 the cell surface agonist-receptor complexes 1357:1399 the cell surface agonist-receptor complexes 1357:1399 The loss of the cell surface agonist-receptor complexes was very rapid in the cells expressing eel FSHR-wt and FSHR-N288Q mutants. 36361582 6 70 theme expression 1085:1094 arg1 level 1096:1100 a negligible expression level 1072:1100 a negligible expression level 1072:1100 The expression level of the N191Q mutant was only 9.2% relative to that of the eel FSHR-wt, indicating a negligible expression level. 36361582 4 71 theme dose-dependent 638:651 arg1 manner 653:658 a dose-dependent manner 636:658 a dose-dependent manner 636:658 In the eel FSHR wild-type (wt), the cAMP response was gradually increased in a dose-dependent manner (0.01-1500 ng/mL), displaying a high response (approximately 57.5 nM/104 cells) at the Rmax level. 36361582 7 72 theme expression 1107:1116 arg1 levels 1118:1123 The expression levels 1103:1123 The expression levels of the N120Q and N272Q mutants 1103:1154 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 7 72 theme expression 1107:1116 arg1 FSHG-wt 1196:1202 the FSHG-wt 1192:1202 the FSHG-wt 1192:1202 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 7 72 theme expression 1107:1116 arg1 % 1179:1179 % 1179:1179 % 1179:1179 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 9 73 theme complexes 1391:1399 arg1 loss 1349:1352 The loss 1345:1352 The loss of the cell surface agonist-receptor complexes 1345:1399 The loss of the cell surface agonist-receptor complexes was very rapid in the cells expressing eel FSHR-wt and FSHR-N288Q mutants. 36361582 9 73 theme complexes 1391:1399 arg1 rapid 1410:1414 rapid 1410:1414 rapid 1410:1414 The loss of the cell surface agonist-receptor complexes was very rapid in the cells expressing eel FSHR-wt and FSHR-N288Q mutants. 36361582 2 74 from sites 323:327 arg1 FSHR 336:339 eel FSHR 332:339 eel FSHR 332:339 We conducted the present study to determine whether conserved glycosylated sites in eel FSHR are necessary for cyclic adenosine monophosphate (cAMP) signal transduction. 36361582 0 75 theme Follicle-Stimulating 85:104 arg1 Receptor 114:121 Eel Follicle-Stimulating Hormone Receptor 81:121 Eel Follicle-Stimulating Hormone Receptor 81:121 The N-Linked Glycosylation Site N191 Is Necessary for PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor. 36361582 12 76 theme G 1771:1771 arg1 proteins 1773:1780 G proteins 1771:1780 G proteins 1771:1780 This finding implies that the cAMP response, mediated by G proteins, is directly related to the loss of cell surface receptors as a result of high-agonist treatment. 36361582 10 77 theme agonist 1621:1627 arg1 concentration 1600:1612 a high concentration 1593:1612 a high concentration of the agonist 1593:1627 Specifically, the N191Q mutant was completely impaired by the loss of cell surface receptors, despite treatment with a high concentration of the agonist. 36361582 11 78 theme cAMP 1688:1691 arg1 transduction 1700:1711 cAMP signal transduction 1688:1711 cAMP signal transduction 1688:1711 Therefore, we suggest that the N191 site is necessary for cAMP signal transduction. 36361582 6 79 theme N191Q 997:1001 arg1 mutant 1003:1008 the N191Q mutant 993:1008 the N191Q mutant 993:1008 The expression level of the N191Q mutant was only 9.2% relative to that of the eel FSHR-wt, indicating a negligible expression level. 36361582 8 80 theme N288Q 1223:1227 arg1 mutant 1229:1234 The N288Q mutant 1219:1234 The N288Q mutant 1219:1234 The N288Q mutant had an expression level similar to that of the eel FSHR-wt, despite the mostly impaired cAMP responsiveness. 36361582 0 81 theme N-Linked 4:11 arg1 Site 27:30 The N-Linked Glycosylation Site N191 0:35 The N-Linked Glycosylation Site N191 0:35 The N-Linked Glycosylation Site N191 Is Necessary for PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor. 36361582 0 81 theme N-Linked 4:11 arg1 Necessary 40:48 Necessary 40:48 Necessary 40:48 The N-Linked Glycosylation Site N191 Is Necessary for PKA Signal Transduction in Eel Follicle-Stimulating Hormone Receptor. 36361582 7 82 dep N120Q 1132:1136 arg1 mutants 1148:1154 mutants 1148:1154 mutants 1148:1154 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 7 82 dep N120Q 1132:1136 arg1 the 1128:1130 the 1128:1130 the 1128:1130 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 9 83 theme eel 1440:1442 arg1 FSHR-wt 1444:1450 eel FSHR-wt 1440:1450 eel FSHR-wt 1440:1450 The loss of the cell surface agonist-receptor complexes was very rapid in the cells expressing eel FSHR-wt and FSHR-N288Q mutants. 36361582 6 84 theme expression 973:982 arg1 % 1022:1022 9.2% 1019:1022 9.2% relative to that of the eel FSHR-wt 1019:1058 The expression level of the N191Q mutant was only 9.2% relative to that of the eel FSHR-wt, indicating a negligible expression level. 36361582 6 84 theme expression 973:982 arg1 level 984:988 The expression level 969:988 The expression level of the N191Q mutant 969:1008 The expression level of the N191Q mutant was only 9.2% relative to that of the eel FSHR-wt, indicating a negligible expression level. 36361582 8 85 theme expression 1243:1252 arg1 level 1254:1258 an expression level 1240:1258 an expression level similar to that of the eel FSHR-wt 1240:1293 The N288Q mutant had an expression level similar to that of the eel FSHR-wt, despite the mostly impaired cAMP responsiveness. 36361582 8 86 theme similar 1260:1266 arg1 level 1254:1258 an expression level 1240:1258 an expression level similar to that of the eel FSHR-wt 1240:1293 The N288Q mutant had an expression level similar to that of the eel FSHR-wt, despite the mostly impaired cAMP responsiveness. 36361582 3 87 used used 421:424 arg2 We 418:419 We 418:419 We 418:419 We used site-directed mutagenesis to induce four mutations (N120Q, N191Q, N272Q, and N288Q) in the N-linked glycosylation sites of eel FSHR. 36361582 5 88 theme impaired 939:946 arg1 transduction 955:966 a completely impaired signal transduction 926:966 a completely impaired signal transduction 926:966 Three mutants (N120Q, N272Q, and N288Q) showed a considerably decreased signal transduction as a result of high-ligand treatment, whereas one mutant (N191Q) exhibited a completely impaired signal transduction. 36361582 10 89 theme receptors 1559:1567 arg1 loss 1538:1541 the loss 1534:1541 the loss of cell surface receptors 1534:1567 Specifically, the N191Q mutant was completely impaired by the loss of cell surface receptors, despite treatment with a high concentration of the agonist. 36361582 6 90 theme relative 1024:1031 arg1 level 984:988 The expression level 969:988 The expression level of the N191Q mutant 969:1008 The expression level of the N191Q mutant was only 9.2% relative to that of the eel FSHR-wt, indicating a negligible expression level. 36361582 6 90 theme relative 1024:1031 arg1 % 1022:1022 9.2% 1019:1022 9.2% relative to that of the eel FSHR-wt 1019:1058 The expression level of the N191Q mutant was only 9.2% relative to that of the eel FSHR-wt, indicating a negligible expression level. 36361582 4 91 theme nM/104 726:731 arg1 response 697:704 a high response 690:704 a high response (approximately 57.5 nM/104 cells) 690:738 In the eel FSHR wild-type (wt), the cAMP response was gradually increased in a dose-dependent manner (0.01-1500 ng/mL), displaying a high response (approximately 57.5 nM/104 cells) at the Rmax level. 36361582 4 91 theme nM/104 726:731 arg1 cells 733:737 approximately 57.5 nM/104 cells 707:737 approximately 57.5 nM/104 cells 707:737 In the eel FSHR wild-type (wt), the cAMP response was gradually increased in a dose-dependent manner (0.01-1500 ng/mL), displaying a high response (approximately 57.5 nM/104 cells) at the Rmax level. 36361582 10 92 theme cell 1546:1549 arg1 receptors 1559:1567 cell surface receptors 1546:1567 cell surface receptors 1546:1567 Specifically, the N191Q mutant was completely impaired by the loss of cell surface receptors, despite treatment with a high concentration of the agonist. 36361582 4 93 dep increased 623:631 arg1 ng/mL 671:675 0.01-1500 ng/mL 661:675 0.01-1500 ng/mL 661:675 In the eel FSHR wild-type (wt), the cAMP response was gradually increased in a dose-dependent manner (0.01-1500 ng/mL), displaying a high response (approximately 57.5 nM/104 cells) at the Rmax level. 36361582 7 94 theme N272Q 1142:1146 arg1 levels 1118:1123 The expression levels 1103:1123 The expression levels of the N120Q and N272Q mutants 1103:1154 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 7 94 theme N272Q 1142:1146 arg1 FSHG-wt 1196:1202 the FSHG-wt 1192:1202 the FSHG-wt 1192:1202 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36361582 7 94 theme N272Q 1142:1146 arg1 % 1179:1179 % 1179:1179 % 1179:1179 The expression levels of the N120Q and N272Q mutants were approximately 35.9% and 24% of the FSHG-wt, respectively. 36079241 2 0 theme potential 606:614 arg1 administration 624:637 potential vaginal administration 606:637 potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides 606:873 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 2 1 theme polysaccharides 859:873 arg1 properties 841:850 the mucoadhesive properties 824:850 the mucoadhesive properties of the polysaccharides 824:873 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 2 1 theme polysaccharides 859:873 arg1 profile 812:818 the sustained drug release profile 785:818 the sustained drug release profile 785:818 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 6 2 theme designed 1447:1454 arg1 hydrogels 1456:1464 the designed hydrogels 1443:1464 the designed hydrogels 1443:1464 In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. 36079241 1 3 theme properties 268:277 arg1 variability 253:263 their variability 247:263 their variability of properties (particle size, ζ-potential, and pH-sensitivity) 247:326 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 3 4 theme ALG 1040:1042 arg1 chains 1044:1049 ALG chains 1040:1049 ALG chains 1040:1049 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 1 5 theme active 466:471 arg1 substances 488:497 active pharmaceutical substances 466:497 active pharmaceutical substances 466:497 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 1 6 theme particle 280:287 arg1 properties 268:277 properties 268:277 properties (particle size, ζ-potential, and pH-sensitivity) 268:326 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 1 6 theme particle 280:287 arg1 size 289:292 particle size 280:292 particle size 280:292 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 3 7 theme entanglement 1024:1035 arg1 hydrogels 888:896 The desired hydrogels 876:896 The desired hydrogels 876:896 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 3 7 theme entanglement 1024:1035 arg1 result 915:920 a result 913:920 a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds 913:1097 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 5 8 from microparticles 1234:1247 arg1 composition 1265:1275 the hydrogel composition 1252:1275 the hydrogel composition 1252:1275 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 0 9 theme Polyelectrolyte 79:93 arg1 Complex 95:101 Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex 43:101 Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex 43:101 pH-Sensitive Drug Delivery System Based on Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex. 36079241 2 10 theme due 773:775 arg1 action 766:771 prolonged pharmacological action 740:771 prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides 740:873 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 2 11 theme CNWs 571:574 arg1 PECs 563:566 PECs 563:566 PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides 563:873 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 2 12 theme release 804:810 arg1 profile 812:818 the sustained drug release profile 785:818 the sustained drug release profile 785:818 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 6 13 theme MET 1481:1483 arg1 MET 1481:1483 MET 1481:1483 MET 1481:1483 In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. 36079241 6 13 theme MET 1481:1483 arg1 % 1476:1476 37 and 67% 1467:1476 37 and 67% of MET 1467:1483 In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. 36079241 4 14 theme delivery 1120:1127 arg1 systems 1129:1135 Metronidazole (MET) delivery systems 1100:1135 Metronidazole (MET) delivery systems with the desired properties 1100:1163 Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. 36079241 2 15 from action 766:771 arg1 environment 716:726 an acidic vaginal environment 698:726 an acidic vaginal environment 698:726 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 1 16 theme polymeric 405:413 arg1 nanoplatforms 415:427 polymeric nanoplatforms 405:427 polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances 405:497 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 7 17 theme CNWs 1567:1570 arg1 introduction 1551:1562 The introduction 1547:1562 The introduction of CNWs into the MET-ALG system 1547:1594 The introduction of CNWs into the MET-ALG system not only prolonged the drug release, but also increased the mucoadhesive properties by about 1.3 times. 36079241 2 18 theme sodium 580:585 arg1 ALG 597:599 ALG 597:599 ALG 597:599 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 2 18 theme sodium 580:585 arg1 alginate 587:594 sodium alginate 580:594 sodium alginate (ALG) 580:600 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 2 19 from release 687:693 arg1 environment 716:726 an acidic vaginal environment 698:726 an acidic vaginal environment 698:726 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 1 20 theme sustained 436:444 arg1 profile 454:460 a sustained release profile 434:460 a sustained release profile for active pharmaceutical substances 434:497 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 8 21 theme CNW-ALG 1712:1718 arg1 hydrogels 1720:1728 novel CNW-ALG hydrogels 1706:1728 novel CNW-ALG hydrogels 1706:1728 Thus, novel CNW-ALG hydrogels are promising carriers for pH sensitive drug delivery carriers. 36079241 8 21 theme CNW-ALG 1712:1718 arg1 carriers 1744:1751 promising carriers 1734:1751 promising carriers for pH sensitive drug delivery carriers 1734:1791 Thus, novel CNW-ALG hydrogels are promising carriers for pH sensitive drug delivery carriers. 36079241 1 22 with nanoplatforms 415:427 arg1 profile 454:460 a sustained release profile 434:460 a sustained release profile for active pharmaceutical substances 434:497 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 1 23 dep properties 268:277 arg1 ζ-potential 295:305 ζ-potential 295:305 ζ-potential 295:305 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 1 23 dep properties 268:277 arg1 pH-sensitivity 312:325 pH-sensitivity 312:325 pH-sensitivity 312:325 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 1 23 dep properties 268:277 arg1 size 289:292 particle size 280:292 particle size 280:292 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 1 23 dep properties 268:277 arg1 properties 268:277 properties 268:277 properties (particle size, ζ-potential, and pH-sensitivity) 268:326 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 2 24 theme pharmacological 750:764 arg1 action 766:771 prolonged pharmacological action 740:771 prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides 740:873 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 5 25 theme apparent 1284:1291 arg1 diameter 1306:1313 an apparent hydrodynamic diameter 1281:1313 an apparent hydrodynamic diameter of approximately 1.7 µm 1281:1337 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 0 26 theme Alginate 70:77 arg1 Complex 95:101 Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex 43:101 Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex 43:101 pH-Sensitive Drug Delivery System Based on Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex. 36079241 6 27 theme pH-sensitive 1412:1423 arg1 release 1430:1436 a prolonged pH-sensitive drug release 1400:1436 a prolonged pH-sensitive drug release from the designed hydrogels 1400:1464 In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. 36079241 1 28 theme deacetylated 157:168 arg1 CNWs 191:194 CNWs 191:194 CNWs 191:194 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 1 28 theme deacetylated 157:168 arg1 nanowhiskers 177:188 partially deacetylated chitin nanowhiskers 147:188 partially deacetylated chitin nanowhiskers (CNWs) 147:195 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 1 29 theme preparation 345:355 arg1 conditions 357:366 the preparation conditions 341:366 the preparation conditions 341:366 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 3 30 theme hydrogen 1084:1091 arg1 bonds 1093:1097 additional hydrogen bonds 1073:1097 additional hydrogen bonds 1073:1097 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 2 31 theme antibiotic 676:685 arg1 release 687:693 controlled pH-dependent antibiotic release 652:693 controlled pH-dependent antibiotic release in an acidic vaginal environment 652:726 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 5 32 theme hydrogel 1256:1263 arg1 composition 1265:1275 the hydrogel composition 1252:1275 the hydrogel composition 1252:1275 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 3 33 theme electrostatic 930:942 arg1 interactions 944:955 electrostatic interactions 930:955 electrostatic interactions between CNWs 930:968 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 2 34 theme controlled 652:661 arg1 release 687:693 controlled pH-dependent antibiotic release 652:693 controlled pH-dependent antibiotic release in an acidic vaginal environment 652:726 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 5 35 theme µm 1336:1337 arg1 ζ-potential 1345:1355 a ζ-potential 1343:1355 a ζ-potential of -43 mV 1343:1365 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 5 35 theme µm 1336:1337 arg1 diameter 1306:1313 an apparent hydrodynamic diameter 1281:1313 an apparent hydrodynamic diameter of approximately 1.7 µm 1281:1337 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 8 36 theme drug 1770:1773 arg1 carriers 1784:1791 pH sensitive drug delivery carriers 1757:1791 pH sensitive drug delivery carriers 1757:1791 Thus, novel CNW-ALG hydrogels are promising carriers for pH sensitive drug delivery carriers. 36079241 7 37 theme drug 1619:1622 arg1 release 1624:1630 the drug release 1615:1630 the drug release 1615:1630 The introduction of CNWs into the MET-ALG system not only prolonged the drug release, but also increased the mucoadhesive properties by about 1.3 times. 36079241 2 38 theme acidic 701:706 arg1 environment 716:726 an acidic vaginal environment 698:726 an acidic vaginal environment 698:726 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 0 39 theme pH-Sensitive 0:11 arg1 System 27:32 pH-Sensitive Drug Delivery System 0:32 pH-Sensitive Drug Delivery System 0:32 pH-Sensitive Drug Delivery System Based on Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex. 36079241 0 40 theme Delivery 18:25 arg1 System 27:32 pH-Sensitive Drug Delivery System 0:32 pH-Sensitive Drug Delivery System 0:32 pH-Sensitive Drug Delivery System Based on Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex. 36079241 0 41 theme Chitin 43:48 arg1 Complex 95:101 Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex 43:101 Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex 43:101 pH-Sensitive Drug Delivery System Based on Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex. 36079241 6 42 from hydrogels 1456:1464 arg1 release 1430:1436 a prolonged pH-sensitive drug release 1400:1436 a prolonged pH-sensitive drug release from the designed hydrogels 1400:1464 In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. 36079241 5 43 theme mV 1364:1365 arg1 ζ-potential 1345:1355 a ζ-potential 1343:1355 a ζ-potential of -43 mV 1343:1365 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 5 43 theme mV 1364:1365 arg1 diameter 1306:1313 an apparent hydrodynamic diameter 1281:1313 an apparent hydrodynamic diameter of approximately 1.7 µm 1281:1337 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 4 44 theme desired 1146:1152 arg1 properties 1154:1163 the desired properties 1142:1163 the desired properties 1142:1163 Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. 36079241 1 45 theme pharmaceutical 473:486 arg1 substances 488:497 active pharmaceutical substances 466:497 active pharmaceutical substances 466:497 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 7 46 theme MET-ALG 1581:1587 arg1 system 1589:1594 the MET-ALG system 1577:1594 the MET-ALG system 1577:1594 The introduction of CNWs into the MET-ALG system not only prolonged the drug release, but also increased the mucoadhesive properties by about 1.3 times. 36079241 2 47 theme vaginal 616:622 arg1 administration 624:637 potential vaginal administration 606:637 potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides 606:873 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 3 48 theme chains 1044:1049 arg1 entanglement 1024:1035 entanglement 1024:1035 entanglement 1024:1035 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 1 49 theme anionic 201:207 arg1 polysaccharides 209:223 anionic polysaccharides 201:223 anionic polysaccharides 201:223 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 2 50 theme drug 799:802 arg1 profile 812:818 the sustained drug release profile 785:818 the sustained drug release profile 785:818 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 1 51 theme nanoplatforms 415:427 arg1 development 390:400 the development 386:400 the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances 386:497 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 5 52 contain had 1277:1279 arg2 ζ-potential 1345:1355 a ζ-potential 1343:1355 a ζ-potential of -43 mV 1343:1365 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 5 52 contain had 1277:1279 arg1 microparticles 1234:1247 The MET-CNW-ALG microparticles 1218:1247 The MET-CNW-ALG microparticles in the hydrogel composition 1218:1275 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 5 52 contain had 1277:1279 arg2 diameter 1306:1313 an apparent hydrodynamic diameter 1281:1313 an apparent hydrodynamic diameter of approximately 1.7 µm 1281:1337 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 2 53 theme alginate 587:594 arg1 PECs 563:566 PECs 563:566 PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides 563:873 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 4 54 theme CNW 1196:1198 arg1 ratio 1204:1208 an CNW:ALG ratio 1193:1208 an CNW:ALG ratio of 1:2 1193:1215 Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. 36079241 4 55 theme 1:2 1213:1215 arg1 ratio 1204:1208 an CNW:ALG ratio 1193:1208 an CNW:ALG ratio of 1:2 1193:1215 Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. 36079241 4 55 theme 1:2 1213:1215 arg1 pH 1182:1183 pH 5.5 1182:1187 pH 5.5 1182:1187 Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. 36079241 6 56 theme release 1377:1383 arg1 studies 1385:1391 In vitro release studies 1368:1391 In vitro release studies 1368:1391 In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. 36079241 1 57 theme release 446:452 arg1 profile 454:460 a sustained release profile 434:460 a sustained release profile for active pharmaceutical substances 434:497 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 8 58 theme novel 1706:1710 arg1 hydrogels 1720:1728 novel CNW-ALG hydrogels 1706:1728 novel CNW-ALG hydrogels 1706:1728 Thus, novel CNW-ALG hydrogels are promising carriers for pH sensitive drug delivery carriers. 36079241 8 58 theme novel 1706:1710 arg1 carriers 1744:1751 promising carriers 1734:1751 promising carriers for pH sensitive drug delivery carriers 1734:1791 Thus, novel CNW-ALG hydrogels are promising carriers for pH sensitive drug delivery carriers. 36079241 3 59 theme desired 880:886 arg1 hydrogels 888:896 The desired hydrogels 876:896 The desired hydrogels 876:896 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 3 59 theme desired 880:886 arg1 result 915:920 a result 913:920 a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds 913:1097 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 2 60 theme prolonged 740:748 arg1 action 766:771 prolonged pharmacological action 740:771 prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides 740:873 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 6 61 theme In 1368:1369 arg1 studies 1385:1391 In vitro release studies 1368:1391 In vitro release studies 1368:1391 In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. 36079241 3 62 theme additional 1073:1082 arg1 bonds 1093:1097 additional hydrogen bonds 1073:1097 additional hydrogen bonds 1073:1097 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 1 63 theme chitin 170:175 arg1 CNWs 191:194 CNWs 191:194 CNWs 191:194 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 1 63 theme chitin 170:175 arg1 nanowhiskers 177:188 partially deacetylated chitin nanowhiskers 147:188 partially deacetylated chitin nanowhiskers (CNWs) 147:195 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 7 64 theme mucoadhesive 1656:1667 arg1 properties 1669:1678 the mucoadhesive properties 1652:1678 the mucoadhesive properties 1652:1678 The introduction of CNWs into the MET-ALG system not only prolonged the drug release, but also increased the mucoadhesive properties by about 1.3 times. 36079241 3 65 theme formation 1060:1068 arg1 hydrogels 888:896 The desired hydrogels 876:896 The desired hydrogels 876:896 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 3 65 theme formation 1060:1068 arg1 result 915:920 a result 913:920 a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds 913:1097 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 8 66 theme promising 1734:1742 arg1 hydrogels 1720:1728 novel CNW-ALG hydrogels 1706:1728 novel CNW-ALG hydrogels 1706:1728 Thus, novel CNW-ALG hydrogels are promising carriers for pH sensitive drug delivery carriers. 36079241 8 66 theme promising 1734:1742 arg1 carriers 1744:1751 promising carriers 1734:1751 promising carriers for pH sensitive drug delivery carriers 1734:1791 Thus, novel CNW-ALG hydrogels are promising carriers for pH sensitive drug delivery carriers. 36079241 2 67 theme hydrogels 544:552 arg1 development 529:539 the development 525:539 the development of hydrogels 525:552 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 2 68 theme pH-dependent 663:674 arg1 release 687:693 controlled pH-dependent antibiotic release 652:693 controlled pH-dependent antibiotic release in an acidic vaginal environment 652:726 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 6 69 dep In 1368:1369 arg1 vitro 1371:1375 vitro 1371:1375 vitro 1371:1375 In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. 36079241 3 70 theme interactions 944:955 arg1 hydrogels 888:896 The desired hydrogels 876:896 The desired hydrogels 876:896 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 3 70 theme interactions 944:955 arg1 result 915:920 a result 913:920 a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds 913:1097 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 2 71 theme vaginal 708:714 arg1 environment 716:726 an acidic vaginal environment 698:726 an acidic vaginal environment 698:726 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 0 72 theme Drug 13:16 arg1 System 27:32 pH-Sensitive Drug Delivery System 0:32 pH-Sensitive Drug Delivery System 0:32 pH-Sensitive Drug Delivery System Based on Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex. 36079241 3 73 theme bonds 1093:1097 arg1 formation 983:991 PEC formation 979:991 PEC formation 979:991 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 3 73 theme bonds 1093:1097 arg1 formation 1060:1068 the formation 1056:1068 the formation of additional hydrogen bonds 1056:1097 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 3 73 theme bonds 1093:1097 arg1 interactions 944:955 electrostatic interactions 930:955 electrostatic interactions between CNWs 930:968 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 3 73 theme bonds 1093:1097 arg1 ALG 974:976 ALG 974:976 ALG (PEC formation) 974:992 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 8 74 theme sensitive 1760:1768 arg1 carriers 1784:1791 pH sensitive drug delivery carriers 1757:1791 pH sensitive drug delivery carriers 1757:1791 Thus, novel CNW-ALG hydrogels are promising carriers for pH sensitive drug delivery carriers. 36079241 1 75 theme Polyelectrolyte 104:118 arg1 complexes 120:128 Polyelectrolyte complexes 104:128 Polyelectrolyte complexes (PECs) 104:135 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 1 75 theme Polyelectrolyte 104:118 arg1 PECs 131:134 PECs 131:134 PECs 131:134 Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. 36079241 5 76 theme hydrodynamic 1293:1304 arg1 diameter 1306:1313 an apparent hydrodynamic diameter 1281:1313 an apparent hydrodynamic diameter of approximately 1.7 µm 1281:1337 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36079241 6 77 theme drug 1425:1428 arg1 release 1430:1436 a prolonged pH-sensitive drug release 1400:1436 a prolonged pH-sensitive drug release from the designed hydrogels 1400:1464 In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. 36079241 8 78 theme delivery 1775:1782 arg1 carriers 1784:1791 pH sensitive drug delivery carriers 1757:1791 pH sensitive drug delivery carriers 1757:1791 Thus, novel CNW-ALG hydrogels are promising carriers for pH sensitive drug delivery carriers. 36079241 3 79 theme ALG 974:976 arg1 hydrogels 888:896 The desired hydrogels 876:896 The desired hydrogels 876:896 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 3 79 theme ALG 974:976 arg1 result 915:920 a result 913:920 a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds 913:1097 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 2 80 theme sustained 789:797 arg1 profile 812:818 the sustained drug release profile 785:818 the sustained drug release profile 785:818 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 6 81 theme prolonged 1402:1410 arg1 release 1430:1436 a prolonged pH-sensitive drug release 1400:1436 a prolonged pH-sensitive drug release from the designed hydrogels 1400:1464 In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. 36079241 0 82 theme Nanowhiskers-Sodium 50:68 arg1 Complex 95:101 Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex 43:101 Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex 43:101 pH-Sensitive Drug Delivery System Based on Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex. 36079241 4 83 with systems 1129:1135 arg1 properties 1154:1163 the desired properties 1142:1163 the desired properties 1142:1163 Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. 36079241 4 84 theme ALG 1200:1202 arg1 ratio 1204:1208 an CNW:ALG ratio 1193:1208 an CNW:ALG ratio of 1:2 1193:1215 Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. 36079241 3 85 theme PEC 979:981 arg1 formation 983:991 PEC formation 979:991 PEC formation 979:991 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 3 85 theme PEC 979:981 arg1 ALG 974:976 ALG 974:976 ALG (PEC formation) 974:992 The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. 36079241 2 86 theme mucoadhesive 828:839 arg1 properties 841:850 the mucoadhesive properties 824:850 the mucoadhesive properties of the polysaccharides 824:873 This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. 36079241 4 87 theme Metronidazole 1100:1112 arg1 systems 1129:1135 Metronidazole (MET) delivery systems 1100:1135 Metronidazole (MET) delivery systems with the desired properties 1100:1163 Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. 36079241 5 88 theme MET-CNW-ALG 1222:1232 arg1 microparticles 1234:1247 The MET-CNW-ALG microparticles 1218:1247 The MET-CNW-ALG microparticles in the hydrogel composition 1218:1275 The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. 36612199 8 0 theme STIM1 1140:1144 arg1 glycosylation 1155:1167 STIM1 N-linked glycosylation 1140:1167 STIM1 N-linked glycosylation 1140:1167 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 6 1 theme MDA-MB-231 906:915 arg1 cells 917:921 MCF10A, MCF7 and MDA-MB-231 cells 889:921 cells 917:921 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 36612199 4 2 theme breast 577:582 arg1 cells 595:599 non-tumoral breast epithelial cells 565:599 non-tumoral breast epithelial cells 565:599 Here we show that treatment of non-tumoral breast epithelial cells with tunicamycin attenuates SOCE. 36612199 6 3 theme glycosylation-deficient 817:839 arg1 Orai1N223A 855:864 Orai1N223A 855:864 Orai1N223A 855:864 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 36612199 6 3 theme glycosylation-deficient 817:839 arg1 mutant 847:852 the glycosylation-deficient Orai1 mutant 813:852 the glycosylation-deficient Orai1 mutant (Orai1N223A) 813:865 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 36612199 8 4 theme glycosylation 1155:1167 arg1 impairment 1126:1135 impairment 1126:1135 impairment of STIM1 N-linked glycosylation 1126:1167 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 6 5 theme MCF7 897:900 arg1 cells 917:921 MCF10A, MCF7 and MDA-MB-231 cells 889:921 cells 917:921 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 36612199 9 6 theme N-linked 1653:1660 arg1 glycosylation 1662:1674 STIM1 N-linked glycosylation 1647:1674 STIM1 N-linked glycosylation 1647:1674 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 4 7 theme cells 595:599 arg1 treatment 552:560 treatment 552:560 treatment of non-tumoral breast epithelial cells with tunicamycin 552:616 Here we show that treatment of non-tumoral breast epithelial cells with tunicamycin attenuates SOCE. 36612199 6 8 from SOCE 881:884 arg1 cells 917:921 MCF10A, MCF7 and MDA-MB-231 cells 889:921 cells 917:921 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 36612199 4 9 with treatment 552:560 arg1 tunicamycin 606:616 tunicamycin 606:616 tunicamycin 606:616 Here we show that treatment of non-tumoral breast epithelial cells with tunicamycin attenuates SOCE. 36612199 1 10 theme N-linked 110:117 arg1 modification 157:168 a post-translational modification 136:168 a post-translational modification that affects protein function, structure, and interaction with other proteins 136:246 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 1 10 theme N-linked 110:117 arg1 glycosylation 119:131 N-linked glycosylation 110:131 N-linked glycosylation 110:131 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 8 11 theme cancer 1243:1248 arg1 cells 1250:1254 breast cancer cells 1236:1254 breast cancer cells 1236:1254 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 7 12 theme MDA-MB-231 1087:1096 arg1 cells 1098:1102 MDA-MB-231 cells 1087:1102 MDA-MB-231 cells 1087:1102 However, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. 36612199 9 13 theme N-linked 1457:1464 arg1 glycosylation 1466:1478 Summarizing, STIM1 N-linked glycosylation 1438:1478 glycosylation 1466:1478 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 8 14 theme -induced 1197:1204 arg1 activation 1216:1225 thapsigargin (TG)-induced caspase-3 activation 1180:1225 thapsigargin (TG)-induced caspase-3 activation 1180:1225 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 9 15 theme Summarizing 1438:1448 arg1 glycosylation 1466:1478 Summarizing, STIM1 N-linked glycosylation 1438:1478 glycosylation 1466:1478 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 8 16 theme smaller 1273:1279 arg1 activity 1291:1298 a smaller caspase-3 activity 1271:1298 a smaller caspase-3 activity 1271:1298 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 7 17 from effect 1060:1065 arg1 SOCE 1070:1073 SOCE 1070:1073 SOCE in MCF7 and MDA-MB-231 cells 1070:1102 However, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. 36612199 5 18 theme luminal 688:694 arg1 MCF7 696:699 luminal MCF7 688:699 luminal MCF7 688:699 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 9 19 theme SOCE 1502:1505 arg1 activation 1507:1516 full SOCE activation 1497:1516 full SOCE activation in non-tumoral breast epithelial cells 1497:1555 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 9 20 theme apoptosis 1732:1740 arg1 resistance 1742:1751 apoptosis resistance 1732:1751 apoptosis resistance 1732:1751 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 9 21 gly glycosylation 1466:1478 arg1 SOCE 1502:1505 full SOCE activation 1497:1516 full SOCE activation in non-tumoral breast epithelial cells 1497:1555 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 2 22 theme entry 273:277 arg1 Orai1 301:305 Orai1 301:305 Orai1 301:305 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 2 22 theme entry 273:277 arg1 proteins 291:298 The store-operated Ca2+ entry (SOCE) core proteins 249:298 The store-operated Ca2+ entry (SOCE) core proteins 249:298 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 2 22 theme entry 273:277 arg1 STIM1 311:315 STIM1 311:315 STIM1 311:315 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 9 23 from SOCE 1571:1574 arg1 MCF7 1593:1596 breast cancer MCF7 and MDA-MB-231 cells 1579:1617 MCF7 1593:1596 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 9 23 from SOCE 1571:1574 arg1 cells 1613:1617 breast cancer MCF7 and MDA-MB-231 cells 1579:1617 cells 1613:1617 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 2 24 theme store-operated 253:266 arg1 SOCE 280:283 SOCE 280:283 SOCE 280:283 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 2 24 theme store-operated 253:266 arg1 entry 273:277 store-operated Ca2+ entry 253:277 The store-operated Ca2+ entry (SOCE) core proteins 249:298 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 7 25 theme mutant 974:979 arg1 expression 933:942 expression 933:942 expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) 933:996 However, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. 36612199 9 26 theme breast 1533:1538 arg1 cells 1551:1555 non-tumoral breast epithelial cells 1521:1555 non-tumoral breast epithelial cells 1521:1555 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 0 27 from Entry 23:27 arg1 Cells 46:50 Breast Cancer Cells 32:50 Breast Cancer Cells 32:50 Store-Operated Calcium Entry in Breast Cancer Cells Is Insensitive to Orai1 and STIM1 N-Linked Glycosylation. 36612199 7 28 theme non-glycosylable 951:966 arg1 STIM1N131/171Q 982:995 STIM1N131/171Q 982:995 STIM1N131/171Q 982:995 However, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. 36612199 7 28 theme non-glycosylable 951:966 arg1 mutant 974:979 the non-glycosylable STIM1 mutant 947:979 the non-glycosylable STIM1 mutant (STIM1N131/171Q) 947:996 However, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. 36612199 3 29 theme Abnormal 360:367 arg1 SOCE 369:372 Abnormal SOCE 360:372 Abnormal SOCE 360:372 Abnormal SOCE has been associated to a number of disorders, including cancer, and alterations in Orai1 glycosylation have been related to cancer invasiveness and metastasis. 36612199 0 30 theme STIM1 80:84 arg1 Glycosylation 95:107 STIM1 N-Linked Glycosylation 80:107 STIM1 N-Linked Glycosylation 80:107 Store-Operated Calcium Entry in Breast Cancer Cells Is Insensitive to Orai1 and STIM1 N-Linked Glycosylation. 36612199 2 31 theme core 286:289 arg1 Orai1 301:305 Orai1 301:305 Orai1 301:305 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 2 31 theme core 286:289 arg1 proteins 291:298 The store-operated Ca2+ entry (SOCE) core proteins 249:298 The store-operated Ca2+ entry (SOCE) core proteins 249:298 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 2 31 theme core 286:289 arg1 STIM1 311:315 STIM1 311:315 STIM1 311:315 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 8 32 theme STIM1 1354:1358 arg1 STIM1N131/171Q 1368:1381 STIM1N131/171Q 1368:1381 STIM1N131/171Q 1368:1381 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 8 32 theme STIM1 1354:1358 arg1 mutant 1360:1365 the non-glycosylable STIM1 mutant 1333:1365 the non-glycosylable STIM1 mutant (STIM1N131/171Q) 1333:1382 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 7 33 from SOCE 1070:1073 arg1 MCF7 1078:1081 MCF7 1078:1081 MCF7 1078:1081 However, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. 36612199 7 33 from SOCE 1070:1073 arg1 cells 1098:1102 MDA-MB-231 cells 1087:1102 MDA-MB-231 cells 1087:1102 However, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. 36612199 9 34 link N-linked 1457:1464 arg1 glycosylation 1466:1478 Summarizing, STIM1 N-linked glycosylation 1438:1478 glycosylation 1466:1478 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 6 35 theme MCF10A 889:894 arg1 cells 917:921 MCF10A, MCF7 and MDA-MB-231 cells 889:921 cells 917:921 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 36612199 0 36 theme Store-Operated 0:13 arg1 Entry 23:27 Store-Operated Calcium Entry 0:27 Store-Operated Calcium Entry in Breast Cancer Cells 0:50 Store-Operated Calcium Entry in Breast Cancer Cells Is Insensitive to Orai1 and STIM1 N-Linked Glycosylation. 36612199 3 37 dep cancer 498:503 arg1 invasiveness 505:516 invasiveness 505:516 invasiveness 505:516 Abnormal SOCE has been associated to a number of disorders, including cancer, and alterations in Orai1 glycosylation have been related to cancer invasiveness and metastasis. 36612199 9 38 theme cancer 1586:1591 arg1 MCF7 1593:1596 breast cancer MCF7 and MDA-MB-231 cells 1579:1617 MCF7 1593:1596 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 1 39 theme post-translational 138:155 arg1 modification 157:168 a post-translational modification 136:168 a post-translational modification that affects protein function, structure, and interaction with other proteins 136:246 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 1 39 theme post-translational 138:155 arg1 glycosylation 119:131 N-linked glycosylation 110:131 N-linked glycosylation 110:131 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 0 40 theme Breast 32:37 arg1 Cells 46:50 Breast Cancer Cells 32:50 Breast Cancer Cells 32:50 Store-Operated Calcium Entry in Breast Cancer Cells Is Insensitive to Orai1 and STIM1 N-Linked Glycosylation. 36612199 5 41 from effect 670:675 arg1 TNBC 736:739 TNBC 736:739 TNBC 736:739 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 5 41 from effect 670:675 arg1 cancer 728:733 triple negative breast cancer 705:733 triple negative breast cancer (TNBC) 705:740 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 5 41 from effect 670:675 arg1 MCF7 696:699 luminal MCF7 688:699 luminal MCF7 688:699 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 5 41 from effect 670:675 arg1 SOCE 680:683 SOCE 680:683 SOCE 680:683 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 2 42 gly N-glycosylation 326:340 arg2 motifs 352:357 N-glycosylation consensus motifs 326:357 N-glycosylation consensus motifs 326:357 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 3 43 from alterations 442:452 arg1 glycosylation 463:475 Orai1 glycosylation 457:475 Orai1 glycosylation 457:475 Abnormal SOCE has been associated to a number of disorders, including cancer, and alterations in Orai1 glycosylation have been related to cancer invasiveness and metastasis. 36612199 2 44 theme consensus 342:350 arg1 motifs 352:357 N-glycosylation consensus motifs 326:357 N-glycosylation consensus motifs 326:357 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 1 45 with structure 201:209 arg1 proteins 239:246 other proteins 233:246 other proteins 233:246 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 1 46 link N-linked 110:117 arg1 modification 157:168 a post-translational modification 136:168 a post-translational modification that affects protein function, structure, and interaction with other proteins 136:246 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 1 46 link N-linked 110:117 arg1 glycosylation 119:131 N-linked glycosylation 110:131 N-linked glycosylation 110:131 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 8 47 theme caspase-3 1416:1424 arg1 activation 1426:1435 TG-evoked caspase-3 activation 1406:1435 TG-evoked caspase-3 activation 1406:1435 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 1 48 theme other 233:237 arg1 proteins 239:246 other proteins 233:246 other proteins 233:246 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 1 49 with function 191:198 arg1 proteins 239:246 other proteins 233:246 other proteins 233:246 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 6 50 theme mutant 847:852 arg1 expression 799:808 expression 799:808 expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) 799:865 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 36612199 9 51 theme STIM1 1647:1651 arg1 glycosylation 1662:1674 STIM1 N-linked glycosylation 1647:1674 STIM1 N-linked glycosylation 1647:1674 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 4 52 theme non-tumoral 565:575 arg1 cells 595:599 non-tumoral breast epithelial cells 565:599 non-tumoral breast epithelial cells 565:599 Here we show that treatment of non-tumoral breast epithelial cells with tunicamycin attenuates SOCE. 36612199 8 53 dep TG 1315:1316 arg1 response 1303:1310 response 1303:1310 response 1303:1310 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 8 54 theme N-linked 1146:1153 arg1 glycosylation 1155:1167 STIM1 N-linked glycosylation 1140:1167 STIM1 N-linked glycosylation 1140:1167 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 4 55 theme epithelial 584:593 arg1 cells 595:599 non-tumoral breast epithelial cells 565:599 non-tumoral breast epithelial cells 565:599 Here we show that treatment of non-tumoral breast epithelial cells with tunicamycin attenuates SOCE. 36612199 8 56 from effect 1396:1401 arg1 cells 1250:1254 breast cancer cells 1236:1254 breast cancer cells 1236:1254 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 8 56 from effect 1396:1401 arg1 activation 1426:1435 TG-evoked caspase-3 activation 1406:1435 TG-evoked caspase-3 activation 1406:1435 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 1 57 theme protein 183:189 arg1 function 191:198 protein function 183:198 protein function 183:198 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 9 58 from activation 1507:1516 arg1 cells 1551:1555 non-tumoral breast epithelial cells 1521:1555 non-tumoral breast epithelial cells 1521:1555 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 8 59 theme breast 1236:1241 arg1 cells 1250:1254 breast cancer cells 1236:1254 breast cancer cells 1236:1254 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 9 60 theme STIM1 1451:1455 arg1 glycosylation 1466:1478 Summarizing, STIM1 N-linked glycosylation 1438:1478 glycosylation 1466:1478 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 6 61 theme imaging 765:771 arg1 experiments 773:783 Ca2+ imaging experiments 760:783 Ca2+ imaging experiments 760:783 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 36612199 5 62 theme negative 712:719 arg1 TNBC 736:739 TNBC 736:739 TNBC 736:739 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 5 62 theme negative 712:719 arg1 cancer 728:733 triple negative breast cancer 705:733 triple negative breast cancer (TNBC) 705:740 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 8 63 theme caspase-3 1206:1214 arg1 activation 1216:1225 thapsigargin (TG)-induced caspase-3 activation 1180:1225 thapsigargin (TG)-induced caspase-3 activation 1180:1225 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 9 64 theme full 1497:1500 arg1 activation 1507:1516 full SOCE activation 1497:1516 full SOCE activation in non-tumoral breast epithelial cells 1497:1555 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 8 65 theme caspase-3 1281:1289 arg1 activity 1291:1298 a smaller caspase-3 activity 1271:1298 a smaller caspase-3 activity 1271:1298 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 7 66 theme MCF10A 1031:1036 arg1 cells 1038:1042 MCF10A cells 1031:1042 MCF10A cells 1031:1042 However, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. 36612199 9 67 theme resistance 1742:1751 arg1 development 1717:1727 the development 1713:1727 the development of apoptosis resistance 1713:1751 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 5 68 theme MDA-MB-231 742:751 arg1 cells 753:757 MDA-MB-231 cells 742:757 MDA-MB-231 cells 742:757 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 2 69 theme Ca2+ 268:271 arg1 SOCE 280:283 SOCE 280:283 SOCE 280:283 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 2 69 theme Ca2+ 268:271 arg1 entry 273:277 store-operated Ca2+ entry 253:277 The store-operated Ca2+ entry (SOCE) core proteins 249:298 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 9 70 theme non-tumoral 1521:1531 arg1 cells 1551:1555 non-tumoral breast epithelial cells 1521:1555 non-tumoral breast epithelial cells 1521:1555 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 8 71 link N-linked 1146:1153 arg1 glycosylation 1155:1167 STIM1 N-linked glycosylation 1140:1167 STIM1 N-linked glycosylation 1140:1167 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 9 72 theme epithelial 1540:1549 arg1 cells 1551:1555 non-tumoral breast epithelial cells 1521:1555 non-tumoral breast epithelial cells 1521:1555 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 0 73 theme N-Linked 86:93 arg1 Glycosylation 95:107 STIM1 N-Linked Glycosylation 80:107 STIM1 N-Linked Glycosylation 80:107 Store-Operated Calcium Entry in Breast Cancer Cells Is Insensitive to Orai1 and STIM1 N-Linked Glycosylation. 36612199 7 74 theme STIM1 968:972 arg1 STIM1N131/171Q 982:995 STIM1N131/171Q 982:995 STIM1N131/171Q 982:995 However, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. 36612199 7 74 theme STIM1 968:972 arg1 mutant 974:979 the non-glycosylable STIM1 mutant 947:979 the non-glycosylable STIM1 mutant (STIM1N131/171Q) 947:996 However, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. 36612199 5 75 dep MCF7 696:699 arg1 cells 753:757 MDA-MB-231 cells 742:757 MDA-MB-231 cells 742:757 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 8 76 theme non-glycosylable 1337:1352 arg1 STIM1N131/171Q 1368:1381 STIM1N131/171Q 1368:1381 STIM1N131/171Q 1368:1381 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 8 76 theme non-glycosylable 1337:1352 arg1 mutant 1360:1365 the non-glycosylable STIM1 mutant 1333:1365 the non-glycosylable STIM1 mutant (STIM1N131/171Q) 1333:1382 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 0 77 theme Calcium 15:21 arg1 Entry 23:27 Store-Operated Calcium Entry 0:27 Store-Operated Calcium Entry in Breast Cancer Cells 0:50 Store-Operated Calcium Entry in Breast Cancer Cells Is Insensitive to Orai1 and STIM1 N-Linked Glycosylation. 36612199 8 78 theme mutant 1360:1365 arg1 expression 1319:1328 expression 1319:1328 expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) 1319:1382 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 1 79 with interaction 216:226 arg1 proteins 239:246 other proteins 233:246 other proteins 233:246 N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. 36612199 9 80 theme breast 1579:1584 arg1 MCF7 1593:1596 breast cancer MCF7 and MDA-MB-231 cells 1579:1617 MCF7 1593:1596 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 9 81 link N-linked 1653:1660 arg1 glycosylation 1662:1674 STIM1 N-linked glycosylation 1647:1674 STIM1 N-linked glycosylation 1647:1674 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 3 82 theme Orai1 457:461 arg1 glycosylation 463:475 Orai1 glycosylation 457:475 Orai1 glycosylation 457:475 Abnormal SOCE has been associated to a number of disorders, including cancer, and alterations in Orai1 glycosylation have been related to cancer invasiveness and metastasis. 36612199 0 83 theme Cancer 39:44 arg1 Cells 46:50 Breast Cancer Cells 32:50 Breast Cancer Cells 32:50 Store-Operated Calcium Entry in Breast Cancer Cells Is Insensitive to Orai1 and STIM1 N-Linked Glycosylation. 36612199 3 84 theme disorders 409:417 arg1 cancer 430:435 cancer 430:435 cancer 430:435 Abnormal SOCE has been associated to a number of disorders, including cancer, and alterations in Orai1 glycosylation have been related to cancer invasiveness and metastasis. 36612199 3 84 theme disorders 409:417 arg1 number 399:404 a number 397:404 a number of disorders, including cancer 397:435 Abnormal SOCE has been associated to a number of disorders, including cancer, and alterations in Orai1 glycosylation have been related to cancer invasiveness and metastasis. 36612199 6 85 theme Ca2+ 760:763 arg1 experiments 773:783 Ca2+ imaging experiments 760:783 Ca2+ imaging experiments 760:783 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 36612199 9 86 theme MDA-MB-231 1602:1611 arg1 cells 1613:1617 breast cancer MCF7 and MDA-MB-231 cells 1579:1617 cells 1613:1617 Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. 36612199 5 87 theme breast 721:726 arg1 TNBC 736:739 TNBC 736:739 TNBC 736:739 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 5 87 theme breast 721:726 arg1 cancer 728:733 triple negative breast cancer 705:733 triple negative breast cancer (TNBC) 705:740 Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. 36612199 2 88 theme N-glycosylation 326:340 arg1 motifs 352:357 N-glycosylation consensus motifs 326:357 N-glycosylation consensus motifs 326:357 The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. 36612199 8 89 theme non-tumoral 1108:1118 arg1 cells 1120:1124 non-tumoral cells 1108:1124 non-tumoral cells 1108:1124 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 8 90 theme TG-evoked 1406:1414 arg1 activation 1426:1435 TG-evoked caspase-3 activation 1406:1435 TG-evoked caspase-3 activation 1406:1435 In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. 36612199 6 91 theme Orai1 841:845 arg1 Orai1N223A 855:864 Orai1N223A 855:864 Orai1N223A 855:864 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 36612199 6 91 theme Orai1 841:845 arg1 mutant 847:852 the glycosylation-deficient Orai1 mutant 813:852 the glycosylation-deficient Orai1 mutant (Orai1N223A) 813:865 Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. 37265706 4 0 theme OA 786:787 arg1 specimens 789:797 clinical OA specimens 777:797 clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort 777:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 3 1 from implication 444:454 arg1 pathogenesis 524:535 the OA pathogenesis 517:535 the OA pathogenesis 517:535 The implication of either chondrocyte senescence or protein glycosylation in the OA pathogenesis has been extensively and individually studied. 37265706 1 2 theme common 175:180 arg1 disease 217:223 the most common degenerative and progressive joint disease 166:223 the most common degenerative and progressive joint disease 166:223 Osteoarthritis (OA) is the most common degenerative and progressive joint disease. 37265706 1 2 theme common 175:180 arg1 Osteoarthritis 143:156 Osteoarthritis 143:156 Osteoarthritis (OA) 143:161 Osteoarthritis (OA) is the most common degenerative and progressive joint disease. 37265706 6 3 from addition 1026:1033 arg1 well-connected 1070:1083 well-connected 1070:1083 well-connected 1070:1083 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 6 3 from addition 1026:1033 arg1 signal 1060:1065 the cellular senescence signal 1036:1065 the cellular senescence signal 1036:1065 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 5 4 theme OA 1006:1007 arg1 pathogenesis 1009:1020 OA pathogenesis 1006:1020 OA pathogenesis 1006:1020 We demonstrated that both cellular senescence signal and protein glycosylation pathways in chondrocytes are validly associated with OA pathogenesis. 37265706 1 5 theme degenerative 182:193 arg1 disease 217:223 the most common degenerative and progressive joint disease 166:223 the most common degenerative and progressive joint disease 166:223 Osteoarthritis (OA) is the most common degenerative and progressive joint disease. 37265706 1 5 theme degenerative 182:193 arg1 Osteoarthritis 143:156 Osteoarthritis 143:156 Osteoarthritis (OA) 143:161 Osteoarthritis (OA) is the most common degenerative and progressive joint disease. 37265706 6 6 theme O-linked 1092:1099 arg1 pathway 1115:1121 the O-linked glycosylation pathway 1088:1121 the O-linked glycosylation pathway in OA chondrocyte and vice-versa 1088:1154 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 8 7 theme OA 1507:1508 arg1 features 1495:1502 pathological features 1482:1502 chondrocyte senescence as well as pathological features of OA 1448:1508 Moreover, the expression levels of the GALNT family are prominently associated with chondrocyte senescence as well as pathological features of OA. 37265706 8 7 theme OA 1507:1508 arg1 senescence 1460:1469 chondrocyte senescence 1448:1469 chondrocyte senescence as well as pathological features of OA 1448:1508 Moreover, the expression levels of the GALNT family are prominently associated with chondrocyte senescence as well as pathological features of OA. 37265706 9 8 link O-linked 1606:1613 arg1 glycosylation 1615:1627 O-linked glycosylation 1606:1627 O-linked glycosylation 1606:1627 Collectively, these findings uncover a crucial relationship between chondrocyte senescence and O-linked glycosylation on the OA pathophysiology, thereby revealing a potential target for OA. 37265706 4 9 theme single-cell 738:748 arg1 datasets 765:772 single-cell RNA sequencing datasets 738:772 single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort 738:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 6 10 theme glycosylation 1101:1113 arg1 pathway 1115:1121 the O-linked glycosylation pathway 1088:1121 the O-linked glycosylation pathway in OA chondrocyte and vice-versa 1088:1154 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 0 11 theme osteoarthritis 114:127 arg1 pathogenesis 129:140 osteoarthritis pathogenesis 114:140 osteoarthritis pathogenesis 114:140 Bioinformatic analysis reveals potential relationship between chondrocyte senescence and protein glycosylation in osteoarthritis pathogenesis. 37265706 2 12 theme protein 311:317 arg1 glycosylation 319:331 protein glycosylation 311:331 protein glycosylation 311:331 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 12 theme protein 311:317 arg1 modification 373:384 the most abundant post-translational modification 336:384 the most abundant post-translational modification 336:384 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 13 theme cellular 406:413 arg1 pathways 430:437 various cellular and biological pathways 398:437 various cellular and biological pathways 398:437 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 4 14 theme chondrocyte 657:667 arg1 senescence 669:678 chondrocyte senescence 657:678 chondrocyte senescence 657:678 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 4 15 theme clinical 777:784 arg1 specimens 789:797 clinical OA specimens 777:797 clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort 777:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 5 16 from signal 920:925 arg1 chondrocytes 965:976 chondrocytes 965:976 chondrocytes 965:976 We demonstrated that both cellular senescence signal and protein glycosylation pathways in chondrocytes are validly associated with OA pathogenesis. 37265706 5 17 theme protein 931:937 arg1 pathways 953:960 both cellular senescence signal and protein glycosylation pathways 895:960 pathways 953:960 We demonstrated that both cellular senescence signal and protein glycosylation pathways in chondrocytes are validly associated with OA pathogenesis. 37265706 4 18 theme Expression 821:830 arg1 database 840:847 the Gene Expression Omnibus database 812:847 the Gene Expression Omnibus database with a different cohort 812:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 8 19 theme pathological 1482:1493 arg1 features 1495:1502 pathological features 1482:1502 chondrocyte senescence as well as pathological features of OA 1448:1508 Moreover, the expression levels of the GALNT family are prominently associated with chondrocyte senescence as well as pathological features of OA. 37265706 4 20 theme sequencing 754:763 arg1 datasets 765:772 single-cell RNA sequencing datasets 738:772 single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort 738:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 3 21 theme glycosylation 500:512 arg1 implication 444:454 The implication 440:454 The implication of either chondrocyte senescence or protein glycosylation in the OA pathogenesis 440:535 The implication of either chondrocyte senescence or protein glycosylation in the OA pathogenesis has been extensively and individually studied. 37265706 4 22 from relationship 636:647 arg1 pathogenesis 713:724 the pathogenesis 709:724 the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort 709:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 7 23 theme family 1240:1245 arg1 levels 1172:1177 The expression levels 1157:1177 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, 1157:1319 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. 37265706 4 24 theme different 856:864 arg1 cohort 866:871 a different cohort 854:871 a different cohort 854:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 1 25 theme progressive 199:209 arg1 disease 217:223 the most common degenerative and progressive joint disease 166:223 the most common degenerative and progressive joint disease 166:223 Osteoarthritis (OA) is the most common degenerative and progressive joint disease. 37265706 1 25 theme progressive 199:209 arg1 Osteoarthritis 143:156 Osteoarthritis 143:156 Osteoarthritis (OA) 143:161 Osteoarthritis (OA) is the most common degenerative and progressive joint disease. 37265706 9 26 theme potential 1676:1684 arg1 target 1686:1691 a potential target 1674:1691 a potential target for OA 1674:1698 Collectively, these findings uncover a crucial relationship between chondrocyte senescence and O-linked glycosylation on the OA pathophysiology, thereby revealing a potential target for OA. 37265706 0 27 from relationship 41:52 arg1 pathogenesis 129:140 osteoarthritis pathogenesis 114:140 osteoarthritis pathogenesis 114:140 Bioinformatic analysis reveals potential relationship between chondrocyte senescence and protein glycosylation in osteoarthritis pathogenesis. 37265706 7 28 theme OA 1347:1348 arg1 chondrocytes 1350:1361 OA chondrocytes 1347:1361 OA chondrocytes 1347:1361 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. 37265706 2 29 theme abundant 345:352 arg1 glycosylation 319:331 protein glycosylation 311:331 protein glycosylation 311:331 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 29 theme abundant 345:352 arg1 modification 373:384 the most abundant post-translational modification 336:384 the most abundant post-translational modification 336:384 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 6 30 dep OA 1126:1127 arg1 chondrocyte 1129:1139 chondrocyte 1129:1139 chondrocyte 1129:1139 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 6 30 dep OA 1126:1127 arg1 OA 1126:1127 OA chondrocyte and vice-versa 1126:1154 OA chondrocyte and vice-versa 1126:1154 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 6 30 dep OA 1126:1127 arg1 vice-versa 1145:1154 vice-versa 1145:1154 vice-versa 1145:1154 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 1 31 theme joint 211:215 arg1 disease 217:223 the most common degenerative and progressive joint disease 166:223 the most common degenerative and progressive joint disease 166:223 Osteoarthritis (OA) is the most common degenerative and progressive joint disease. 37265706 1 31 theme joint 211:215 arg1 Osteoarthritis 143:156 Osteoarthritis 143:156 Osteoarthritis (OA) 143:161 Osteoarthritis (OA) is the most common degenerative and progressive joint disease. 37265706 0 32 theme Bioinformatic 0:12 arg1 analysis 14:21 Bioinformatic analysis 0:21 Bioinformatic analysis 0:21 Bioinformatic analysis reveals potential relationship between chondrocyte senescence and protein glycosylation in osteoarthritis pathogenesis. 37265706 6 33 from pathway 1115:1121 arg1 chondrocyte 1129:1139 chondrocyte 1129:1139 chondrocyte 1129:1139 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 6 33 from pathway 1115:1121 arg1 OA 1126:1127 OA chondrocyte and vice-versa 1126:1154 OA chondrocyte and vice-versa 1126:1154 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 6 33 from pathway 1115:1121 arg1 vice-versa 1145:1154 vice-versa 1145:1154 vice-versa 1145:1154 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 4 34 theme Gene 816:819 arg1 database 840:847 the Gene Expression Omnibus database 812:847 the Gene Expression Omnibus database with a different cohort 812:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 8 35 theme expression 1378:1387 arg1 levels 1389:1394 the expression levels 1374:1394 the expression levels of the GALNT family 1374:1414 Moreover, the expression levels of the GALNT family are prominently associated with chondrocyte senescence as well as pathological features of OA. 37265706 3 36 theme protein 492:498 arg1 glycosylation 500:512 protein glycosylation 492:512 protein glycosylation 492:512 The implication of either chondrocyte senescence or protein glycosylation in the OA pathogenesis has been extensively and individually studied. 37265706 0 37 theme potential 31:39 arg1 relationship 41:52 potential relationship 31:52 potential relationship between chondrocyte senescence and protein glycosylation in osteoarthritis pathogenesis 31:140 Bioinformatic analysis reveals potential relationship between chondrocyte senescence and protein glycosylation in osteoarthritis pathogenesis. 37265706 5 38 theme cellular 900:907 arg1 signal 920:925 both cellular senescence signal and protein glycosylation pathways 895:960 signal 920:925 We demonstrated that both cellular senescence signal and protein glycosylation pathways in chondrocytes are validly associated with OA pathogenesis. 37265706 6 39 from well-connected 1070:1083 arg1 addition 1026:1033 addition 1026:1033 addition 1026:1033 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 8 40 theme chondrocyte 1448:1458 arg1 senescence 1460:1469 chondrocyte senescence 1448:1469 chondrocyte senescence as well as pathological features of OA 1448:1508 Moreover, the expression levels of the GALNT family are prominently associated with chondrocyte senescence as well as pathological features of OA. 37265706 9 41 theme O-linked 1606:1613 arg1 glycosylation 1615:1627 O-linked glycosylation 1606:1627 O-linked glycosylation 1606:1627 Collectively, these findings uncover a crucial relationship between chondrocyte senescence and O-linked glycosylation on the OA pathophysiology, thereby revealing a potential target for OA. 37265706 6 42 link O-linked 1092:1099 arg1 pathway 1115:1121 the O-linked glycosylation pathway 1088:1121 the O-linked glycosylation pathway in OA chondrocyte and vice-versa 1088:1154 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 4 43 theme possible 627:634 arg1 relationship 636:647 the possible relationship 623:647 the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort 623:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 7 44 theme N-acetylgalactosaminyltransferase 1198:1230 arg1 family 1240:1245 the polypeptide N-acetylgalactosaminyltransferase (GALNT) family 1182:1245 the polypeptide N-acetylgalactosaminyltransferase (GALNT) family 1182:1245 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. 37265706 7 44 theme N-acetylgalactosaminyltransferase 1198:1230 arg1 essential 1257:1265 essential 1257:1265 essential 1257:1265 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. 37265706 7 45 from stage 1314:1318 arg1 biosynthesis 1275:1286 the biosynthesis 1271:1286 the biosynthesis of O-Glycans at the early stage 1271:1318 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. 37265706 2 46 theme various 398:404 arg1 pathways 430:437 various cellular and biological pathways 398:437 various cellular and biological pathways 398:437 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 5 47 theme senescence 909:918 arg1 signal 920:925 both cellular senescence signal and protein glycosylation pathways 895:960 signal 920:925 We demonstrated that both cellular senescence signal and protein glycosylation pathways in chondrocytes are validly associated with OA pathogenesis. 37265706 3 48 theme chondrocyte 466:476 arg1 senescence 478:487 chondrocyte senescence 466:487 chondrocyte senescence 466:487 The implication of either chondrocyte senescence or protein glycosylation in the OA pathogenesis has been extensively and individually studied. 37265706 8 49 theme GALNT 1403:1407 arg1 family 1409:1414 the GALNT family 1399:1414 the GALNT family 1399:1414 Moreover, the expression levels of the GALNT family are prominently associated with chondrocyte senescence as well as pathological features of OA. 37265706 5 50 theme glycosylation 939:951 arg1 pathways 953:960 both cellular senescence signal and protein glycosylation pathways 895:960 pathways 953:960 We demonstrated that both cellular senescence signal and protein glycosylation pathways in chondrocytes are validly associated with OA pathogenesis. 37265706 2 51 theme cycle 270:274 arg1 senescence 235:244 Cellular senescence 226:244 Cellular senescence 226:244 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 51 theme cycle 270:274 arg1 arrest 276:281 an irreversible cell cycle arrest 249:281 an irreversible cell cycle arrest progressive with age 249:302 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 4 52 theme RNA 750:752 arg1 datasets 765:772 single-cell RNA sequencing datasets 738:772 single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort 738:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 4 53 theme OA 729:730 arg1 pathogenesis 713:724 the pathogenesis 709:724 the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort 709:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 3 54 theme senescence 478:487 arg1 implication 444:454 The implication 440:454 The implication of either chondrocyte senescence or protein glycosylation in the OA pathogenesis 440:535 The implication of either chondrocyte senescence or protein glycosylation in the OA pathogenesis has been extensively and individually studied. 37265706 2 55 with progressive 283:293 arg1 age 300:302 age 300:302 age 300:302 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 56 theme cell 265:268 arg1 senescence 235:244 Cellular senescence 226:244 Cellular senescence 226:244 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 56 theme cell 265:268 arg1 arrest 276:281 an irreversible cell cycle arrest 249:281 an irreversible cell cycle arrest progressive with age 249:302 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 3 57 theme OA 521:522 arg1 pathogenesis 524:535 the OA pathogenesis 517:535 the OA pathogenesis 517:535 The implication of either chondrocyte senescence or protein glycosylation in the OA pathogenesis has been extensively and individually studied. 37265706 4 58 with database 840:847 arg1 cohort 866:871 a different cohort 854:871 a different cohort 854:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 7 59 theme expression 1161:1170 arg1 levels 1172:1177 The expression levels 1157:1177 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, 1157:1319 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. 37265706 2 60 theme irreversible 252:263 arg1 senescence 235:244 Cellular senescence 226:244 Cellular senescence 226:244 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 60 theme irreversible 252:263 arg1 arrest 276:281 an irreversible cell cycle arrest 249:281 an irreversible cell cycle arrest progressive with age 249:302 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 5 61 from pathways 953:960 arg1 chondrocytes 965:976 chondrocytes 965:976 chondrocytes 965:976 We demonstrated that both cellular senescence signal and protein glycosylation pathways in chondrocytes are validly associated with OA pathogenesis. 37265706 8 62 theme family 1409:1414 arg1 levels 1389:1394 the expression levels 1374:1394 the expression levels of the GALNT family 1374:1414 Moreover, the expression levels of the GALNT family are prominently associated with chondrocyte senescence as well as pathological features of OA. 37265706 0 63 theme chondrocyte 62:72 arg1 senescence 74:83 chondrocyte senescence 62:83 chondrocyte senescence 62:83 Bioinformatic analysis reveals potential relationship between chondrocyte senescence and protein glycosylation in osteoarthritis pathogenesis. 37265706 6 64 theme cellular 1040:1047 arg1 well-connected 1070:1083 well-connected 1070:1083 well-connected 1070:1083 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 6 64 theme cellular 1040:1047 arg1 signal 1060:1065 the cellular senescence signal 1036:1065 the cellular senescence signal 1036:1065 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 7 65 theme polypeptide 1186:1196 arg1 GALNT 1233:1237 GALNT 1233:1237 GALNT 1233:1237 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. 37265706 7 65 theme polypeptide 1186:1196 arg1 N-acetylgalactosaminyltransferase 1198:1230 polypeptide N-acetylgalactosaminyltransferase 1186:1230 the polypeptide N-acetylgalactosaminyltransferase (GALNT) family 1182:1245 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. 37265706 9 66 theme OA 1636:1637 arg1 pathophysiology 1639:1653 the OA pathophysiology 1632:1653 the OA pathophysiology 1632:1653 Collectively, these findings uncover a crucial relationship between chondrocyte senescence and O-linked glycosylation on the OA pathophysiology, thereby revealing a potential target for OA. 37265706 4 67 theme specimens 789:797 arg1 datasets 765:772 single-cell RNA sequencing datasets 738:772 single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort 738:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 7 68 theme O-Glycans 1291:1299 arg1 biosynthesis 1275:1286 the biosynthesis 1271:1286 the biosynthesis of O-Glycans at the early stage 1271:1318 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. 37265706 4 69 theme protein 684:690 arg1 glycosylation 692:704 protein glycosylation 684:704 protein glycosylation 684:704 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 2 70 theme Cellular 226:233 arg1 senescence 235:244 Cellular senescence 226:244 Cellular senescence 226:244 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 70 theme Cellular 226:233 arg1 arrest 276:281 an irreversible cell cycle arrest 249:281 an irreversible cell cycle arrest progressive with age 249:302 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 4 71 theme Omnibus 832:838 arg1 database 840:847 the Gene Expression Omnibus database 812:847 the Gene Expression Omnibus database with a different cohort 812:871 In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. 37265706 2 72 theme post-translational 354:371 arg1 glycosylation 319:331 protein glycosylation 311:331 protein glycosylation 311:331 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 72 theme post-translational 354:371 arg1 modification 373:384 the most abundant post-translational modification 336:384 the most abundant post-translational modification 336:384 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 0 73 theme protein 89:95 arg1 glycosylation 97:109 protein glycosylation 89:109 protein glycosylation 89:109 Bioinformatic analysis reveals potential relationship between chondrocyte senescence and protein glycosylation in osteoarthritis pathogenesis. 37265706 2 74 theme progressive 283:293 arg1 senescence 235:244 Cellular senescence 226:244 Cellular senescence 226:244 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 74 theme progressive 283:293 arg1 arrest 276:281 an irreversible cell cycle arrest 249:281 an irreversible cell cycle arrest progressive with age 249:302 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 2 75 theme biological 419:428 arg1 pathways 430:437 various cellular and biological pathways 398:437 various cellular and biological pathways 398:437 Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. 37265706 9 76 theme chondrocyte 1579:1589 arg1 senescence 1591:1600 chondrocyte senescence 1579:1600 chondrocyte senescence 1579:1600 Collectively, these findings uncover a crucial relationship between chondrocyte senescence and O-linked glycosylation on the OA pathophysiology, thereby revealing a potential target for OA. 37265706 9 77 theme crucial 1550:1556 arg1 relationship 1558:1569 a crucial relationship 1548:1569 a crucial relationship between chondrocyte senescence and O-linked glycosylation 1548:1627 Collectively, these findings uncover a crucial relationship between chondrocyte senescence and O-linked glycosylation on the OA pathophysiology, thereby revealing a potential target for OA. 37265706 7 78 theme early 1308:1312 arg1 stage 1314:1318 the early stage 1304:1318 the early stage 1304:1318 The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. 37265706 6 79 theme senescence 1049:1058 arg1 well-connected 1070:1083 well-connected 1070:1083 well-connected 1070:1083 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 37265706 6 79 theme senescence 1049:1058 arg1 signal 1060:1065 the cellular senescence signal 1036:1065 the cellular senescence signal 1036:1065 In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. 35829791 7 0 gly glycopeptides 1437:1449 arg2 glycopeptides 1437:1449 glycopeptides 1437:1449 glycopeptides enriched by any HILIC sorbent 1437:1479 To the best of our knowledge, this is the highest number of glycopeptides enriched by any HILIC sorbent. 35829791 4 1 theme standard 1091:1098 arg1 digest 1100:1105 each standard digest 1086:1105 each standard digest 1086:1105 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 1 2 from samples 366:372 arg1 N-glycopeptides 320:334 intact N-glycopeptides 313:334 intact N-glycopeptides from standards and biological samples 313:372 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 2 from samples 366:372 arg1 enrichment 299:308 the enrichment 295:308 the enrichment of intact N-glycopeptides from standards and biological samples 295:372 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 2 3 theme enrichment 404:413 arg1 efficiency 415:424 good enrichment efficiency 399:424 good enrichment efficiency 399:424 Terpolymer-Cya provides good enrichment efficiency, improved hydrophilicity, and selectivity by virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid. 35829791 3 4 gly glycopeptides 725:737 arg2 glycopeptides 725:737 24 N-linked glycopeptides 713:737 24 N-linked glycopeptides 713:737 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 5 theme model 801:805 arg1 glycoproteins 807:819 model glycoproteins 801:819 model glycoproteins 801:819 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 6 6 theme nano-liquid 1312:1322 arg1 nLC-MS/MS 1365:1373 nLC-MS/MS 1365:1373 nLC-MS/MS 1365:1373 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 6 6 theme nano-liquid 1312:1322 arg1 spectrometry 1351:1362 nano-liquid chromatography-tandem mass spectrometry 1312:1362 nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) 1312:1374 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 3 7 theme acid-functionalized 605:623 arg1 HILIC 682:686 HILIC 682:686 HILIC 682:686 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 7 theme acid-functionalized 605:623 arg1 chromatography 666:679 acid-functionalized polymeric hydrophilic interaction liquid chromatography 605:679 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent 597:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 1 8 theme polymeric 114:122 arg1 dimethacrylate/1,2-epoxy-5-hexene 161:193 methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene 125:193 methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene 125:193 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 8 theme polymeric 114:122 arg1 base/matrix 196:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix 108:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix 108:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 4 9 theme Zwitterionic 899:910 arg1 chemistry 912:920 Zwitterionic chemistry 899:920 Zwitterionic chemistry of cysteine 899:932 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 6 10 theme glycopeptides 1294:1306 arg1 profile 1263:1269 a profile 1261:1269 a profile of 807 intact N-linked glycopeptides 1261:1306 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 8 11 gly glycoproteins 1491:1503 arg1 glycoproteins 1491:1503 Selected glycoproteins 1482:1503 Selected glycoproteins 1482:1503 Selected glycoproteins are evaluated in link to various cancers including the breast, lung, uterine, and melanoma using single-nucleotide variances (BioMuta). 35829791 6 12 theme intact 1278:1283 arg1 glycopeptides 1294:1306 807 intact N-linked glycopeptides 1274:1306 807 intact N-linked glycopeptides 1274:1306 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 3 13 theme liquid 659:664 arg1 HILIC 682:686 HILIC 682:686 HILIC 682:686 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 13 theme liquid 659:664 arg1 chromatography 666:679 acid-functionalized polymeric hydrophilic interaction liquid chromatography 605:679 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent 597:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 6 14 theme mass 1346:1349 arg1 nLC-MS/MS 1365:1373 nLC-MS/MS 1365:1373 nLC-MS/MS 1365:1373 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 6 14 theme mass 1346:1349 arg1 spectrometry 1351:1362 nano-liquid chromatography-tandem mass spectrometry 1312:1362 nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) 1312:1374 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 9 15 theme successful 1726:1735 arg1 strategy 1712:1719 an in-house developed strategy 1690:1719 an in-house developed strategy 1690:1719 This study represents the complete idea of using an in-house developed strategy as a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers. 35829791 9 15 theme successful 1726:1735 arg1 tool 1737:1740 a successful tool 1724:1740 a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers 1724:1829 This study represents the complete idea of using an in-house developed strategy as a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers. 35829791 4 16 with attomoles 1035:1043 arg1 profile 1075:1081 a complete glycosylation profile 1050:1081 a complete glycosylation profile of each standard digest 1050:1105 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 1 17 from enrichment 299:308 arg1 standards 341:349 standards 341:349 standards 341:349 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 17 from enrichment 299:308 arg1 samples 366:372 biological samples 355:372 biological samples 355:372 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 3 18 theme hydrophilic 635:645 arg1 HILIC 682:686 HILIC 682:686 HILIC 682:686 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 18 theme hydrophilic 635:645 arg1 chromatography 666:679 acid-functionalized polymeric hydrophilic interaction liquid chromatography 605:679 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent 597:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 8 19 theme Selected 1482:1489 arg1 glycoproteins 1491:1503 Selected glycoproteins 1482:1503 Selected glycoproteins 1482:1503 Selected glycoproteins are evaluated in link to various cancers including the breast, lung, uterine, and melanoma using single-nucleotide variances (BioMuta). 35829791 7 20 theme highest 1419:1425 arg1 this 1407:1410 this 1407:1410 this 1407:1410 To the best of our knowledge, this is the highest number of glycopeptides enriched by any HILIC sorbent. 35829791 7 20 theme highest 1419:1425 arg1 number 1427:1432 the highest number 1415:1432 the highest number of glycopeptides enriched by any HILIC sorbent 1415:1479 To the best of our knowledge, this is the highest number of glycopeptides enriched by any HILIC sorbent. 35829791 1 21 theme hydrophilic 260:270 arg1 Cya 286:288 Cya 286:288 Cya 286:288 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 21 theme hydrophilic 260:270 arg1 acid 280:283 zwitterionic hydrophilic cysteic acid 247:283 zwitterionic hydrophilic cysteic acid (Cya) 247:289 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 6 22 theme chromatography-tandem 1324:1344 arg1 nLC-MS/MS 1365:1373 nLC-MS/MS 1365:1373 nLC-MS/MS 1365:1373 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 6 22 theme chromatography-tandem 1324:1344 arg1 spectrometry 1351:1362 nano-liquid chromatography-tandem mass spectrometry 1312:1362 nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) 1312:1374 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 4 23 theme BSA 977:979 arg1 1:200 989:993 1:200 989:993 1:200 989:993 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 4 23 theme BSA 977:979 arg1 digest 981:986 BSA digest 977:986 BSA digest (1:200) 977:994 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 1 24 theme methacrylate/ethylene 132:152 arg1 dimethacrylate/1,2-epoxy-5-hexene 161:193 methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene 125:193 methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene 125:193 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 24 theme methacrylate/ethylene 132:152 arg1 base/matrix 196:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix 108:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix 108:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 2 25 theme zwitterionic 550:561 arg1 property 563:570 the zwitterionic property 546:570 the zwitterionic property offered by cysteic acid 546:594 Terpolymer-Cya provides good enrichment efficiency, improved hydrophilicity, and selectivity by virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid. 35829791 6 26 theme human 1240:1244 arg1 serum 1246:1250 human serum 1240:1250 human serum 1240:1250 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 9 27 theme glycoprotein-based 1778:1795 arg1 issues 1806:1811 glycoprotein-based clinical issues 1778:1811 glycoprotein-based clinical issues regarding cancers 1778:1829 This study represents the complete idea of using an in-house developed strategy as a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers. 35829791 0 28 theme intact 78:83 arg1 analysis 98:105 serum intact glycopeptide analysis 72:105 serum intact glycopeptide analysis 72:105 Terpolymeric platform with enhanced hydrophilicity via cysteic acid for serum intact glycopeptide analysis. 35829791 2 29 theme cysteic 583:589 arg1 acid 591:594 cysteic acid 583:594 cysteic acid 583:594 Terpolymer-Cya provides good enrichment efficiency, improved hydrophilicity, and selectivity by virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid. 35829791 3 30 dep G 843:843 arg1 i.e. 822:825 i.e. 822:825 i.e. 822:825 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 4 31 theme detection 1007:1015 arg1 limit 1017:1021 lower detection limit 1001:1021 lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest 1001:1105 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 5 32 theme reproducibility 1137:1151 arg1 recovery 1112:1119 The recovery 1108:1119 The recovery of 81% and good reproducibility 1108:1151 The recovery of 81% and good reproducibility define the application of terpolymer-Cya for complex samples like a serum. 35829791 0 33 gly glycopeptide 85:96 arg2 glycopeptide 85:96 serum intact glycopeptide analysis 72:105 serum intact glycopeptide analysis 72:105 Terpolymeric platform with enhanced hydrophilicity via cysteic acid for serum intact glycopeptide analysis. 35829791 4 34 theme down 1023:1026 arg1 limit 1017:1021 lower detection limit 1001:1021 lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest 1001:1105 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 9 35 theme developed 1702:1710 arg1 strategy 1712:1719 an in-house developed strategy 1690:1719 an in-house developed strategy 1690:1719 This study represents the complete idea of using an in-house developed strategy as a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers. 35829791 9 35 theme developed 1702:1710 arg1 tool 1737:1740 a successful tool 1724:1740 a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers 1724:1829 This study represents the complete idea of using an in-house developed strategy as a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers. 35829791 2 36 theme area 496:499 arg1 virtue 471:476 virtue 471:476 virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid 471:594 Terpolymer-Cya provides good enrichment efficiency, improved hydrophilicity, and selectivity by virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid. 35829791 2 37 theme better 481:486 arg1 area 496:499 better surface area 481:499 better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid 481:594 Terpolymer-Cya provides good enrichment efficiency, improved hydrophilicity, and selectivity by virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid. 35829791 2 37 theme better 481:486 arg1 m2/g 513:516 2.09 × 102 m2/g 502:516 2.09 × 102 m2/g 502:516 Terpolymer-Cya provides good enrichment efficiency, improved hydrophilicity, and selectivity by virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid. 35829791 1 38 theme N-glycopeptides 320:334 arg1 enrichment 299:308 the enrichment 295:308 the enrichment of intact N-glycopeptides from standards and biological samples 295:372 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 39 theme new 110:112 arg1 dimethacrylate/1,2-epoxy-5-hexene 161:193 methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene 125:193 methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene 125:193 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 39 theme new 110:112 arg1 base/matrix 196:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix 108:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix 108:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 3 40 theme SPE 743:745 arg1 mode 772:775 SPE (solid phase extraction) mode 743:775 SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively 743:896 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 40 theme SPE 743:745 arg1 extraction 760:769 solid phase extraction 748:769 solid phase extraction 748:769 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 4 41 theme complete 1052:1059 arg1 profile 1075:1081 a complete glycosylation profile 1050:1081 a complete glycosylation profile of each standard digest 1050:1105 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 8 42 theme single-nucleotide 1602:1618 arg1 variances 1620:1628 single-nucleotide variances 1602:1628 single-nucleotide variances (BioMuta) 1602:1638 Selected glycoproteins are evaluated in link to various cancers including the breast, lung, uterine, and melanoma using single-nucleotide variances (BioMuta). 35829791 8 42 theme single-nucleotide 1602:1618 arg1 BioMuta 1631:1637 BioMuta 1631:1637 BioMuta 1631:1637 Selected glycoproteins are evaluated in link to various cancers including the breast, lung, uterine, and melanoma using single-nucleotide variances (BioMuta). 35829791 2 43 theme good 399:402 arg1 efficiency 415:424 good enrichment efficiency 399:424 good enrichment efficiency 399:424 Terpolymer-Cya provides good enrichment efficiency, improved hydrophilicity, and selectivity by virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid. 35829791 0 44 theme cysteic 55:61 arg1 acid 63:66 cysteic acid 55:66 cysteic acid for serum intact glycopeptide analysis 55:105 Terpolymeric platform with enhanced hydrophilicity via cysteic acid for serum intact glycopeptide analysis. 35829791 1 45 theme biological 355:364 arg1 samples 366:372 biological samples 355:372 biological samples 355:372 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 46 theme cysteic 272:278 arg1 Cya 286:288 Cya 286:288 Cya 286:288 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 46 theme cysteic 272:278 arg1 acid 280:283 zwitterionic hydrophilic cysteic acid 247:283 zwitterionic hydrophilic cysteic acid (Cya) 247:289 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 3 47 theme solid 748:752 arg1 mode 772:775 SPE (solid phase extraction) mode 743:775 SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively 743:896 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 47 theme solid 748:752 arg1 extraction 760:769 solid phase extraction 748:769 solid phase extraction 748:769 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 2 48 theme improved 427:434 arg1 hydrophilicity 436:449 improved hydrophilicity 427:449 improved hydrophilicity 427:449 Terpolymer-Cya provides good enrichment efficiency, improved hydrophilicity, and selectivity by virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid. 35829791 4 49 theme digest 1100:1105 arg1 profile 1075:1081 a complete glycosylation profile 1050:1081 a complete glycosylation profile of each standard digest 1050:1105 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 3 50 theme tryptic 782:788 arg1 digests 790:796 tryptic digests 782:796 tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively 782:896 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 4 51 theme cysteine 925:932 arg1 chemistry 912:920 Zwitterionic chemistry 899:920 Zwitterionic chemistry of cysteine 899:932 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 1 52 from standards 341:349 arg1 N-glycopeptides 320:334 intact N-glycopeptides 313:334 intact N-glycopeptides from standards and biological samples 313:372 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 52 from standards 341:349 arg1 enrichment 299:308 the enrichment 295:308 the enrichment of intact N-glycopeptides from standards and biological samples 295:372 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 3 53 theme Cysteic 597:603 arg1 sorbent 689:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent 597:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent 597:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 9 54 theme in-house 1693:1700 arg1 strategy 1712:1719 an in-house developed strategy 1690:1719 an in-house developed strategy 1690:1719 This study represents the complete idea of using an in-house developed strategy as a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers. 35829791 9 54 theme in-house 1693:1700 arg1 tool 1737:1740 a successful tool 1724:1740 a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers 1724:1829 This study represents the complete idea of using an in-house developed strategy as a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers. 35829791 3 55 theme glycoproteins 807:819 arg1 digests 790:796 tryptic digests 782:796 tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively 782:896 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 7 56 theme HILIC 1467:1471 arg1 sorbent 1473:1479 any HILIC sorbent 1463:1479 any HILIC sorbent 1463:1479 To the best of our knowledge, this is the highest number of glycopeptides enriched by any HILIC sorbent. 35829791 3 57 from digests 790:796 arg1 mode 772:775 SPE (solid phase extraction) mode 743:775 SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively 743:896 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 57 from digests 790:796 arg1 extraction 760:769 solid phase extraction 748:769 solid phase extraction 748:769 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 6 58 theme N-linked 1285:1292 arg1 glycopeptides 1294:1306 807 intact N-linked glycopeptides 1274:1306 807 intact N-linked glycopeptides 1274:1306 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 3 59 theme interaction 647:657 arg1 HILIC 682:686 HILIC 682:686 HILIC 682:686 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 59 theme interaction 647:657 arg1 chromatography 666:679 acid-functionalized polymeric hydrophilic interaction liquid chromatography 605:679 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent 597:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 6 60 link N-linked 1285:1292 arg1 glycopeptides 1294:1306 807 intact N-linked glycopeptides 1274:1306 807 intact N-linked glycopeptides 1274:1306 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 3 61 theme immunoglobulin 828:841 arg1 IgG 846:848 IgG 846:848 IgG 846:848 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 61 theme immunoglobulin 828:841 arg1 G 843:843 immunoglobulin G 828:843 immunoglobulin G (IgG) 828:849 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 62 theme polymeric 625:633 arg1 HILIC 682:686 HILIC 682:686 HILIC 682:686 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 62 theme polymeric 625:633 arg1 chromatography 666:679 acid-functionalized polymeric hydrophilic interaction liquid chromatography 605:679 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent 597:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 7 63 theme glycopeptides 1437:1449 arg1 this 1407:1410 this 1407:1410 this 1407:1410 To the best of our knowledge, this is the highest number of glycopeptides enriched by any HILIC sorbent. 35829791 7 63 theme glycopeptides 1437:1449 arg1 number 1427:1432 the highest number 1415:1432 the highest number of glycopeptides enriched by any HILIC sorbent 1415:1479 To the best of our knowledge, this is the highest number of glycopeptides enriched by any HILIC sorbent. 35829791 1 64 theme zwitterionic 247:258 arg1 Cya 286:288 Cya 286:288 Cya 286:288 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 64 theme zwitterionic 247:258 arg1 acid 280:283 zwitterionic hydrophilic cysteic acid 247:283 zwitterionic hydrophilic cysteic acid (Cya) 247:289 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 5 65 theme % 1126:1126 arg1 recovery 1112:1119 The recovery 1108:1119 The recovery of 81% and good reproducibility 1108:1151 The recovery of 81% and good reproducibility define the application of terpolymer-Cya for complex samples like a serum. 35829791 3 66 theme chromatography 666:679 arg1 sorbent 689:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent 597:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent 597:695 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 6 67 gly glycopeptides 1294:1306 arg2 glycopeptides 1294:1306 807 intact N-linked glycopeptides 1274:1306 807 intact N-linked glycopeptides 1274:1306 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 4 68 theme higher 953:958 arg1 selectivity 960:970 higher selectivity 953:970 higher selectivity 953:970 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 1 69 gly N-glycopeptides 320:334 arg1 samples 366:372 biological samples 355:372 biological samples 355:372 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 69 gly N-glycopeptides 320:334 arg1 standards 341:349 standards 341:349 standards 341:349 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 69 gly N-glycopeptides 320:334 arg2 N-glycopeptides 320:334 intact N-glycopeptides 313:334 intact N-glycopeptides from standards and biological samples 313:372 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 70 theme methyl 125:130 arg1 dimethacrylate/1,2-epoxy-5-hexene 161:193 methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene 125:193 methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene 125:193 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 70 theme methyl 125:130 arg1 base/matrix 196:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix 108:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix 108:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 8 71 theme various 1530:1536 arg1 melanoma 1587:1594 melanoma 1587:1594 melanoma 1587:1594 Selected glycoproteins are evaluated in link to various cancers including the breast, lung, uterine, and melanoma using single-nucleotide variances (BioMuta). 35829791 8 71 theme various 1530:1536 arg1 lung 1568:1571 lung 1568:1571 lung 1568:1571 Selected glycoproteins are evaluated in link to various cancers including the breast, lung, uterine, and melanoma using single-nucleotide variances (BioMuta). 35829791 8 71 theme various 1530:1536 arg1 cancers 1538:1544 various cancers 1530:1544 various cancers including the breast, lung, uterine, and melanoma using single-nucleotide variances (BioMuta) 1530:1638 Selected glycoproteins are evaluated in link to various cancers including the breast, lung, uterine, and melanoma using single-nucleotide variances (BioMuta). 35829791 8 71 theme various 1530:1536 arg1 breast 1560:1565 breast 1560:1565 breast 1560:1565 Selected glycoproteins are evaluated in link to various cancers including the breast, lung, uterine, and melanoma using single-nucleotide variances (BioMuta). 35829791 8 71 theme various 1530:1536 arg1 uterine 1574:1580 uterine 1574:1580 uterine 1574:1580 Selected glycoproteins are evaluated in link to various cancers including the breast, lung, uterine, and melanoma using single-nucleotide variances (BioMuta). 35829791 6 72 theme serum 1246:1250 arg1 Analysis 1228:1235 Analysis 1228:1235 Analysis of human serum 1228:1250 Analysis of human serum provides a profile of 807 intact N-linked glycopeptides via nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). 35829791 0 73 theme serum 72:76 arg1 analysis 98:105 serum intact glycopeptide analysis 72:105 serum intact glycopeptide analysis 72:105 Terpolymeric platform with enhanced hydrophilicity via cysteic acid for serum intact glycopeptide analysis. 35829791 1 74 theme glycol 154:159 arg1 dimethacrylate/1,2-epoxy-5-hexene 161:193 methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene 125:193 methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene 125:193 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 1 74 theme glycol 154:159 arg1 base/matrix 196:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix 108:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix 108:206 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 3 75 theme horseradish 855:865 arg1 peroxidase 867:876 horseradish peroxidase 855:876 horseradish peroxidase (HRP) 855:882 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 75 theme horseradish 855:865 arg1 HRP 879:881 HRP 879:881 HRP 879:881 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 0 76 theme glycopeptide 85:96 arg1 analysis 98:105 serum intact glycopeptide analysis 72:105 serum intact glycopeptide analysis 72:105 Terpolymeric platform with enhanced hydrophilicity via cysteic acid for serum intact glycopeptide analysis. 35829791 9 77 theme clinical 1797:1804 arg1 issues 1806:1811 glycoprotein-based clinical issues 1778:1811 glycoprotein-based clinical issues regarding cancers 1778:1829 This study represents the complete idea of using an in-house developed strategy as a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers. 35829791 5 78 theme terpolymer-Cya 1179:1192 arg1 application 1164:1174 the application 1160:1174 the application of terpolymer-Cya for complex samples like a serum 1160:1225 The recovery of 81% and good reproducibility define the application of terpolymer-Cya for complex samples like a serum. 35829791 5 79 theme good 1132:1135 arg1 reproducibility 1137:1151 good reproducibility 1132:1151 good reproducibility 1132:1151 The recovery of 81% and good reproducibility define the application of terpolymer-Cya for complex samples like a serum. 35829791 4 80 theme lower 1001:1005 arg1 limit 1017:1021 lower detection limit 1001:1021 lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest 1001:1105 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 4 81 theme glycosylation 1061:1073 arg1 profile 1075:1081 a complete glycosylation profile 1050:1081 a complete glycosylation profile of each standard digest 1050:1105 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 3 82 gly glycoproteins 807:819 arg1 glycoproteins 807:819 model glycoproteins 801:819 model glycoproteins 801:819 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 0 83 theme enhanced 27:34 arg1 hydrophilicity 36:49 enhanced hydrophilicity 27:49 enhanced hydrophilicity via cysteic acid for serum intact glycopeptide analysis 27:105 Terpolymeric platform with enhanced hydrophilicity via cysteic acid for serum intact glycopeptide analysis. 35829791 1 84 theme intact 313:318 arg1 N-glycopeptides 320:334 intact N-glycopeptides 313:334 intact N-glycopeptides from standards and biological samples 313:372 A new polymeric (methyl methacrylate/ethylene glycol dimethacrylate/1,2-epoxy-5-hexene) base/matrix has been fabricated and decorated with zwitterionic hydrophilic cysteic acid (Cya) for the enrichment of intact N-glycopeptides from standards and biological samples. 35829791 2 85 theme surface 488:494 arg1 area 496:499 better surface area 481:499 better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid 481:594 Terpolymer-Cya provides good enrichment efficiency, improved hydrophilicity, and selectivity by virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid. 35829791 2 85 theme surface 488:494 arg1 m2/g 513:516 2.09 × 102 m2/g 502:516 2.09 × 102 m2/g 502:516 Terpolymer-Cya provides good enrichment efficiency, improved hydrophilicity, and selectivity by virtue of better surface area (2.09 × 102 m2/g) provided by terpolymer and the zwitterionic property offered by cysteic acid. 35829791 4 86 gly glycosylation 1061:1073 arg1 digest 1100:1105 each standard digest 1086:1105 each standard digest 1086:1105 Zwitterionic chemistry of cysteine helps in achieving higher selectivity with BSA digest (1:200), and lower detection limit down to 100 attomoles with a complete glycosylation profile of each standard digest. 35829791 3 87 theme 24 N-linked 713:723 arg1 glycopeptides 725:737 24 N-linked glycopeptides 713:737 24 N-linked glycopeptides 713:737 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 5 88 theme complex 1198:1204 arg1 samples 1206:1212 complex samples 1198:1212 complex samples like a serum 1198:1225 The recovery of 81% and good reproducibility define the application of terpolymer-Cya for complex samples like a serum. 35829791 3 89 theme phase 754:758 arg1 mode 772:775 SPE (solid phase extraction) mode 743:775 SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively 743:896 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 3 89 theme phase 754:758 arg1 extraction 760:769 solid phase extraction 748:769 solid phase extraction 748:769 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 35829791 9 90 theme complete 1667:1674 arg1 idea 1676:1679 the complete idea 1663:1679 the complete idea of using an in-house developed strategy as a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers 1663:1829 This study represents the complete idea of using an in-house developed strategy as a successful tool to help analyze, relate, and answer glycoprotein-based clinical issues regarding cancers. 35829791 3 91 link 24 N-linked 713:723 arg1 glycopeptides 725:737 24 N-linked glycopeptides 713:737 24 N-linked glycopeptides 713:737 Cysteic acid-functionalized polymeric hydrophilic interaction liquid chromatography (HILIC) sorbent enriches 35 and 24 N-linked glycopeptides via SPE (solid phase extraction) mode from tryptic digests of model glycoproteins, i.e., immunoglobulin G (IgG) and horseradish peroxidase (HRP), respectively. 37259080 8 0 theme transporters 1267:1278 arg1 expression 1245:1254 the expression 1241:1254 the expression of glucose transporters and glycolytic enzymes 1241:1301 RESULTS Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. 37259080 11 1 theme glycoprotein 1778:1789 arg1 glycosylation 1751:1763 suppressed N-linked glycosylation 1731:1763 suppressed N-linked glycosylation of the viral glycoprotein 1731:1789 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 37259080 6 2 theme LCMV 912:915 arg1 impact 902:907 The impact 898:907 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells 890:952 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. 37259080 8 3 theme glycolytic 1284:1293 arg1 enzymes 1295:1301 glycolytic enzymes 1284:1301 glycolytic enzymes 1284:1301 RESULTS Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. 37259080 4 4 theme cell 680:683 arg1 metabolism 685:694 host cell metabolism 675:694 host cell metabolism 675:694 Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. 37259080 14 5 theme antiviral 2164:2172 arg1 therapies 2174:2182 new, targeted antiviral therapies 2150:2182 new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses 2150:2238 These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses. 37259080 2 6 theme many 341:344 arg1 cells 361:365 many virus-infected cells 341:365 many virus-infected cells 341:365 Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. 37259080 6 7 theme transcription-quantitative 980:1005 arg1 PCR 1007:1009 reverse transcription-quantitative PCR 972:1009 reverse transcription-quantitative PCR 972:1009 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. 37259080 12 8 gly N-glycosylation 1943:1957 arg1 GP-C 1967:1970 LCMV GP-C 1962:1970 LCMV GP-C 1962:1970 CONCLUSIONS Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 37259080 10 9 theme glycolytic 1563:1572 arg1 2-DG 1603:1606 2-DG 1603:1606 2-DG 1603:1606 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 10 9 theme glycolytic 1563:1572 arg1 2-deoxy-D-glucose 1584:1600 the commonly used glycolytic inhibitor 2-deoxy-D-glucose 1545:1600 the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) 1545:1607 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 8 10 theme glucose 1259:1265 arg1 transporters 1267:1278 glucose transporters 1259:1278 glucose transporters 1259:1278 RESULTS Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. 37259080 12 11 theme glucose 1877:1883 arg1 supply 1885:1890 glucose supply 1877:1890 glucose supply 1877:1890 CONCLUSIONS Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 37259080 7 12 theme particles 1203:1211 arg1 production 1173:1182 the production 1169:1182 the production of infectious LCMV particles 1169:1211 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 1 13 theme tumor 234:238 arg1 metabolism 245:254 tumor cell metabolism 234:254 tumor cell metabolism 234:254 BACKGROUND Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. 37259080 7 14 from effects 1110:1116 arg1 production 1173:1182 the production 1169:1182 the production of infectious LCMV particles 1169:1211 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 7 15 theme infectious 1187:1196 arg1 particles 1203:1211 infectious LCMV particles 1187:1211 infectious LCMV particles 1187:1211 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 1 16 theme metabolism 245:254 arg1 hallmarks 221:229 the most prominent hallmarks 202:229 the most prominent hallmarks of tumor cell metabolism 202:254 BACKGROUND Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. 37259080 7 17 theme glucose 1121:1127 arg1 deficiency 1129:1138 glucose deficiency 1121:1138 glucose deficiency 1121:1138 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 8 18 theme glucose 1347:1353 arg1 uptake 1355:1360 increased glucose uptake 1337:1360 increased glucose uptake 1337:1360 RESULTS Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. 37259080 3 19 theme Viral 368:372 arg1 propagation 374:384 Viral propagation 368:384 Viral propagation 368:384 Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. 37259080 6 20 from metabolism 928:937 arg1 cells 948:952 MRC-5 cells 942:952 MRC-5 cells 942:952 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. 37259080 13 21 theme N-linked 2064:2071 arg1 glycosylation 2081:2093 N-linked protein glycosylation 2064:2093 N-linked protein glycosylation 2064:2093 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. 37259080 7 22 theme glycolysis 1144:1153 arg1 inhibition 1155:1164 glycolysis inhibition 1144:1164 glycolysis inhibition 1144:1164 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 0 23 theme glycoprotein 87:98 arg1 N-glycosylation 100:114 glycoprotein N-glycosylation 87:114 glycoprotein N-glycosylation 87:114 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation. 37259080 9 24 theme LCMV-infected 1407:1419 arg1 cells 1421:1425 depriving LCMV-infected cells 1397:1425 depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production 1397:1483 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 0 25 theme lymphocytic 27:37 arg1 propagation 62:72 lymphocytic choriomeningitis virus propagation 27:72 lymphocytic choriomeningitis virus propagation 27:72 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation. 37259080 12 26 theme LCMV 1841:1844 arg1 cycle 1851:1855 the LCMV life cycle 1837:1855 the LCMV life cycle 1837:1855 CONCLUSIONS Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 37259080 12 26 theme LCMV 1841:1844 arg1 dependent 1864:1872 dependent 1864:1872 dependent 1864:1872 CONCLUSIONS Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 37259080 5 27 theme lymphocytic 786:796 arg1 virus 815:819 lymphocytic choriomeningitis virus 786:819 lymphocytic choriomeningitis virus (LCMV) infection 786:836 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 5 27 theme lymphocytic 786:796 arg1 LCMV 822:825 LCMV 822:825 LCMV 822:825 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 1 28 dep Increased 128:136 arg1 BACKGROUND 117:126 BACKGROUND 117:126 BACKGROUND 117:126 BACKGROUND Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. 37259080 14 29 theme arenaviruses 2227:2238 arg1 range 2218:2222 a wider range 2210:2222 a wider range of arenaviruses 2210:2238 These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses. 37259080 9 30 theme glucose 1444:1450 arg1 cells 1421:1425 depriving LCMV-infected cells 1397:1425 depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production 1397:1483 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 14 31 dep new 2150:2152 arg1 targeted 2155:2162 targeted 2155:2162 targeted 2155:2162 These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses. 37259080 7 32 theme western 1061:1067 arg1 analysis 1074:1081 western blot analysis 1061:1081 western blot analysis 1061:1081 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 3 33 theme tumor 413:417 arg1 cells 419:423 highly proliferative tumor cells 392:423 highly proliferative tumor cells 392:423 Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. 37259080 3 34 theme high 499:502 arg1 requirements 534:545 high bioenergetic and biosynthetic requirements 499:545 high bioenergetic and biosynthetic requirements 499:545 Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. 37259080 9 35 theme inhibiting 1455:1464 arg1 production 1474:1483 inhibiting lactate production 1455:1483 inhibiting lactate production 1455:1483 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 9 36 from impact 1492:1497 arg1 propagation 1508:1518 viral propagation 1502:1518 viral propagation 1502:1518 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 9 37 theme production 1474:1483 arg1 cells 1421:1425 depriving LCMV-infected cells 1397:1425 depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production 1397:1483 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 13 38 link N-linked 2064:2071 arg1 glycosylation 2081:2093 N-linked protein glycosylation 2064:2093 N-linked protein glycosylation 2064:2093 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. 37259080 1 39 theme glucose 138:144 arg1 uptake 146:151 BACKGROUND Increased glucose uptake 117:151 BACKGROUND Increased glucose uptake 117:151 BACKGROUND Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. 37259080 10 40 theme LCMV 1657:1660 arg1 particles 1662:1670 infectious LCMV particles 1646:1670 infectious LCMV particles 1646:1670 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 11 41 gly glycosylation 1751:1763 arg1 glycoprotein 1778:1789 the viral glycoprotein 1768:1789 the viral glycoprotein 1768:1789 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 37259080 14 42 theme new 2150:2152 arg1 therapies 2174:2182 new, targeted antiviral therapies 2150:2182 new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses 2150:2238 These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses. 37259080 13 43 theme LCMV 1995:1998 arg1 propagation 2000:2010 LCMV propagation 1995:2010 LCMV propagation 1995:2010 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. 37259080 0 44 theme virus 56:60 arg1 propagation 62:72 lymphocytic choriomeningitis virus propagation 27:72 lymphocytic choriomeningitis virus propagation 27:72 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation. 37259080 5 45 theme family 882:887 arg1 representative 847:860 a model representative 839:860 a model representative of the Arenaviridae family 839:887 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 5 45 theme family 882:887 arg1 infection 828:836 lymphocytic choriomeningitis virus (LCMV) infection 786:836 lymphocytic choriomeningitis virus (LCMV) infection 786:836 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 12 46 theme LCMV 1962:1965 arg1 GP-C 1967:1970 LCMV GP-C 1962:1970 LCMV GP-C 1962:1970 CONCLUSIONS Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 37259080 14 47 theme wider 2212:2216 arg1 range 2218:2222 a wider range 2210:2222 a wider range of arenaviruses 2210:2238 These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses. 37259080 11 48 theme N-linked 1742:1749 arg1 glycosylation 1751:1763 suppressed N-linked glycosylation 1731:1763 suppressed N-linked glycosylation of the viral glycoprotein 1731:1789 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 37259080 2 49 theme metabolic 301:309 arg1 changes 311:317 similar metabolic changes 293:317 similar metabolic changes 293:317 Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. 37259080 6 50 theme glucose 920:926 arg1 metabolism 928:937 glucose metabolism 920:937 glucose metabolism in MRC-5 cells 920:952 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. 37259080 13 51 dep reduces 1987:1993 arg1 inhibiting 2053:2062 inhibiting 2053:2062 inhibiting N-linked protein glycosylation 2053:2093 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. 37259080 13 51 dep reduces 1987:1993 arg1 disrupting 2019:2028 disrupting 2019:2028 disrupting glycolytic flux 2019:2044 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. 37259080 11 52 theme viral 1772:1776 arg1 glycoprotein 1778:1789 the viral glycoprotein 1768:1789 the viral glycoprotein 1768:1789 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 37259080 12 53 theme N-glycosylation 1943:1957 arg1 importance 1929:1938 the importance 1925:1938 the importance of N-glycosylation of LCMV GP-C 1925:1970 CONCLUSIONS Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 37259080 4 54 theme arenavirus 700:709 arg1 infection 711:719 arenavirus infection 700:719 arenavirus infection 700:719 Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. 37259080 10 55 with treatment 1530:1538 arg1 2-DG 1603:1606 2-DG 1603:1606 2-DG 1603:1606 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 10 55 with treatment 1530:1538 arg1 2-deoxy-D-glucose 1584:1600 the commonly used glycolytic inhibitor 2-deoxy-D-glucose 1545:1600 the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) 1545:1607 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 6 56 theme biochemical 1015:1025 arg1 assays 1027:1032 biochemical assays 1015:1032 biochemical assays 1015:1032 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. 37259080 2 57 theme virus-infected 346:359 arg1 cells 361:365 many virus-infected cells 341:365 many virus-infected cells 341:365 Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. 37259080 12 58 dep CONCLUSIONS 1792:1802 arg1 showed 1825:1830 showed 1825:1830 showed that the LCMV life cycle is not dependent on glucose supply or utilization 1825:1905 CONCLUSIONS Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 37259080 4 59 theme host 675:678 arg1 metabolism 685:694 host cell metabolism 675:694 host cell metabolism 675:694 Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. 37259080 11 60 theme 2-DG 1688:1691 arg1 result 1721:1726 the result 1717:1726 the result of suppressed N-linked glycosylation of the viral glycoprotein 1717:1789 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 37259080 11 60 theme 2-DG 1688:1691 arg1 effect 1678:1683 This effect 1673:1683 This effect of 2-DG 1673:1691 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 37259080 1 61 theme prominent 211:219 arg1 hallmarks 221:229 the most prominent hallmarks 202:229 the most prominent hallmarks of tumor cell metabolism 202:254 BACKGROUND Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. 37259080 8 62 theme enzymes 1295:1301 arg1 expression 1245:1254 the expression 1241:1254 the expression of glucose transporters and glycolytic enzymes 1241:1301 RESULTS Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. 37259080 6 63 theme reverse 972:978 arg1 PCR 1007:1009 reverse transcription-quantitative PCR 972:1009 reverse transcription-quantitative PCR 972:1009 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. 37259080 6 64 dep METHODS 890:896 arg1 impact 902:907 The impact 898:907 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells 890:952 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. 37259080 7 65 theme LCMV 1198:1201 arg1 particles 1203:1211 infectious LCMV particles 1187:1211 infectious LCMV particles 1187:1211 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 10 66 theme used 1558:1561 arg1 2-DG 1603:1606 2-DG 1603:1606 2-DG 1603:1606 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 10 66 theme used 1558:1561 arg1 2-deoxy-D-glucose 1584:1600 the commonly used glycolytic inhibitor 2-deoxy-D-glucose 1545:1600 the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) 1545:1607 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 8 67 theme LCMV 1304:1307 arg1 infection 1309:1317 LCMV infection 1304:1317 LCMV infection 1304:1317 RESULTS Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. 37259080 8 68 theme lactate 1365:1371 arg1 excretion 1373:1381 lactate excretion 1365:1381 lactate excretion 1365:1381 RESULTS Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. 37259080 5 69 theme choriomeningitis 798:813 arg1 virus 815:819 lymphocytic choriomeningitis virus 786:819 lymphocytic choriomeningitis virus (LCMV) infection 786:836 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 5 69 theme choriomeningitis 798:813 arg1 LCMV 822:825 LCMV 822:825 LCMV 822:825 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 1 70 theme cell 240:243 arg1 metabolism 245:254 tumor cell metabolism 234:254 tumor cell metabolism 234:254 BACKGROUND Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. 37259080 8 71 dep RESULTS 1214:1220 arg1 changes 1230:1236 changes 1230:1236 changes in the expression of glucose transporters and glycolytic enzymes 1230:1301 RESULTS Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. 37259080 2 72 theme similar 293:299 arg1 changes 311:317 similar metabolic changes 293:317 similar metabolic changes 293:317 Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. 37259080 11 73 gly glycoprotein 1778:1789 arg1 glycoprotein 1778:1789 the viral glycoprotein 1768:1789 the viral glycoprotein 1768:1789 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 37259080 7 74 theme inhibition 1155:1164 arg1 effects 1110:1116 the effects 1106:1116 the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles 1106:1211 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 7 75 theme deficiency 1129:1138 arg1 effects 1110:1116 the effects 1106:1116 the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles 1106:1211 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 8 76 theme increased 1337:1345 arg1 uptake 1355:1360 increased glucose uptake 1337:1360 increased glucose uptake 1337:1360 RESULTS Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. 37259080 1 77 theme aerobic 173:179 arg1 glycolysis 181:190 aerobic glycolysis 173:190 aerobic glycolysis 173:190 BACKGROUND Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. 37259080 13 78 theme protein 2073:2079 arg1 glycosylation 2081:2093 N-linked protein glycosylation 2064:2093 N-linked protein glycosylation 2064:2093 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. 37259080 5 79 theme model 841:845 arg1 representative 847:860 a model representative 839:860 a model representative of the Arenaviridae family 839:887 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 5 79 theme model 841:845 arg1 infection 828:836 lymphocytic choriomeningitis virus (LCMV) infection 786:836 lymphocytic choriomeningitis virus (LCMV) infection 786:836 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 9 80 theme depriving 1397:1405 arg1 cells 1421:1425 depriving LCMV-infected cells 1397:1425 depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production 1397:1483 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 3 81 theme proliferative 399:411 arg1 cells 419:423 highly proliferative tumor cells 392:423 highly proliferative tumor cells 392:423 Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. 37259080 13 82 theme glycolytic 2030:2039 arg1 flux 2041:2044 glycolytic flux 2030:2044 glycolytic flux 2030:2044 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. 37259080 7 83 used used 1088:1091 arg2 analysis 1074:1081 western blot analysis 1061:1081 western blot analysis 1061:1081 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 7 83 used used 1088:1091 arg2 assay 1051:1055 A focus-forming assay 1035:1055 A focus-forming assay 1035:1055 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 5 84 theme virus 815:819 arg1 representative 847:860 a model representative 839:860 a model representative of the Arenaviridae family 839:887 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 5 84 theme virus 815:819 arg1 infection 828:836 lymphocytic choriomeningitis virus (LCMV) infection 786:836 lymphocytic choriomeningitis virus (LCMV) infection 786:836 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 9 85 theme extracellular 1430:1442 arg1 glucose 1444:1450 extracellular glucose 1430:1450 extracellular glucose 1430:1450 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 0 86 gly glycoprotein 87:98 arg1 glycoprotein 87:98 glycoprotein N-glycosylation 87:114 glycoprotein N-glycosylation 87:114 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation. 37259080 12 87 theme life 1846:1849 arg1 cycle 1851:1855 the LCMV life cycle 1837:1855 the LCMV life cycle 1837:1855 CONCLUSIONS Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 37259080 12 87 theme life 1846:1849 arg1 dependent 1864:1872 dependent 1864:1872 dependent 1864:1872 CONCLUSIONS Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 37259080 8 88 from changes 1230:1236 arg1 expression 1245:1254 the expression 1241:1254 the expression of glucose transporters and glycolytic enzymes 1241:1301 RESULTS Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. 37259080 4 89 theme significant 557:567 arg1 progress 569:576 significant progress 557:576 significant progress 557:576 Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. 37259080 10 90 theme inhibitor 1574:1582 arg1 2-DG 1603:1606 2-DG 1603:1606 2-DG 1603:1606 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 10 90 theme inhibitor 1574:1582 arg1 2-deoxy-D-glucose 1584:1600 the commonly used glycolytic inhibitor 2-deoxy-D-glucose 1545:1600 the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) 1545:1607 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 7 91 theme blot 1069:1072 arg1 analysis 1074:1081 western blot analysis 1061:1081 western blot analysis 1061:1081 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 6 92 from impact 902:907 arg1 metabolism 928:937 glucose metabolism 920:937 glucose metabolism in MRC-5 cells 920:952 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. 37259080 3 93 theme bioenergetic 504:515 arg1 requirements 534:545 high bioenergetic and biosynthetic requirements 499:545 high bioenergetic and biosynthetic requirements 499:545 Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. 37259080 9 94 theme lactate 1466:1472 arg1 production 1474:1483 inhibiting lactate production 1455:1483 inhibiting lactate production 1455:1483 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 1 95 theme Increased 128:136 arg1 uptake 146:151 BACKGROUND Increased glucose uptake 117:151 BACKGROUND Increased glucose uptake 117:151 BACKGROUND Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. 37259080 0 96 theme choriomeningitis 39:54 arg1 propagation 62:72 lymphocytic choriomeningitis virus propagation 27:72 lymphocytic choriomeningitis virus propagation 27:72 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation. 37259080 7 97 theme focus-forming 1037:1049 arg1 assay 1051:1055 A focus-forming assay 1035:1055 A focus-forming assay 1035:1055 A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. 37259080 10 98 theme infectious 1646:1655 arg1 particles 1662:1670 infectious LCMV particles 1646:1670 infectious LCMV particles 1646:1670 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 5 99 theme Arenaviridae 869:880 arg1 family 882:887 the Arenaviridae family 865:887 the Arenaviridae family 865:887 Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. 37259080 4 100 theme metabolic 613:621 arg1 changes 623:629 the metabolic changes 609:629 the metabolic changes induced by viruses 609:648 Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. 37259080 11 101 theme suppressed 1731:1740 arg1 glycosylation 1751:1763 suppressed N-linked glycosylation 1731:1763 suppressed N-linked glycosylation of the viral glycoprotein 1731:1789 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 37259080 3 102 theme biosynthetic 521:532 arg1 requirements 534:545 high bioenergetic and biosynthetic requirements 499:545 high bioenergetic and biosynthetic requirements 499:545 Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. 37259080 9 103 theme viral 1502:1506 arg1 propagation 1508:1518 viral propagation 1502:1518 viral propagation 1502:1518 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 6 104 theme MRC-5 942:946 arg1 cells 948:952 MRC-5 cells 942:952 MRC-5 cells 942:952 METHODS The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. 37259080 3 105 theme macromolecular 462:475 arg1 synthesis 477:485 macromolecular synthesis 462:485 macromolecular synthesis 462:485 Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. 37259080 2 106 theme Accumulating 257:268 arg1 evidence 270:277 Accumulating evidence 257:277 Accumulating evidence 257:277 Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. 37259080 9 107 contain had 1485:1487 arg2 impact 1492:1497 no impact 1489:1497 no impact on viral propagation 1489:1518 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 9 107 contain had 1485:1487 arg1 cells 1421:1425 depriving LCMV-infected cells 1397:1425 depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production 1397:1483 Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. 37259080 11 108 link N-linked 1742:1749 arg1 glycosylation 1751:1763 suppressed N-linked glycosylation 1731:1763 suppressed N-linked glycosylation of the viral glycoprotein 1731:1789 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 37259080 12 109 theme GP-C 1967:1970 arg1 N-glycosylation 1943:1957 N-glycosylation 1943:1957 N-glycosylation of LCMV GP-C 1943:1970 CONCLUSIONS Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 37259080 10 110 theme particles 1662:1670 arg1 production 1632:1641 the production 1628:1641 the production of infectious LCMV particles 1628:1670 However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. 37259080 11 111 theme glycosylation 1751:1763 arg1 result 1721:1726 the result 1717:1726 the result of suppressed N-linked glycosylation of the viral glycoprotein 1717:1789 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 37259080 11 111 theme glycosylation 1751:1763 arg1 effect 1678:1683 This effect 1673:1683 This effect of 2-DG 1673:1691 This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. 35798744 5 0 theme site 834:837 arg1 fucosylation 853:864 site specific core fucosylation 834:864 site specific core fucosylation of glycoproteins 834:881 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 6 1 theme complex 1164:1170 arg1 mixtures 1180:1187 complex protein mixtures 1164:1187 complex protein mixtures 1164:1187 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 3 2 theme core 568:571 arg1 fucosylation 573:584 site-specific core fucosylation 554:584 site-specific core fucosylation of glycoproteins 554:601 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 4 3 gly fucosylated 747:757 arg1 glycans 768:774 core fucosylated N-linked glycans 742:774 core fucosylated N-linked glycans 742:774 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 4 4 theme PNGase 650:655 arg1 treatment 659:667 PNGase F treatment 650:667 PNGase F treatment 650:667 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 0 5 theme glycopeptides 84:96 arg1 treatments 63:72 sequential enzymatic treatments 42:72 sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis 42:127 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 35798744 2 6 link N-linked 392:399 arg1 glycosylation 401:413 N-linked glycosylation 392:413 N-linked glycosylation 392:413 However, quantitative characterization of core fucosylation remains challenging due to the complexity and heterogeneity of N-linked glycosylation. 35798744 6 7 from characterization 1114:1129 arg1 mixtures 1180:1187 complex protein mixtures 1164:1187 complex protein mixtures 1164:1187 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 6 8 from functions 1247:1255 arg1 diseases 1268:1275 various diseases 1260:1275 various diseases 1260:1275 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 2 9 theme glycosylation 401:413 arg1 heterogeneity 375:387 heterogeneity 375:387 heterogeneity 375:387 However, quantitative characterization of core fucosylation remains challenging due to the complexity and heterogeneity of N-linked glycosylation. 35798744 2 9 theme glycosylation 401:413 arg1 complexity 360:369 complexity 360:369 complexity 360:369 However, quantitative characterization of core fucosylation remains challenging due to the complexity and heterogeneity of N-linked glycosylation. 35798744 6 10 theme core 1134:1137 arg1 fucosylation 1139:1150 core fucosylation 1134:1150 core fucosylation events from complex protein mixtures 1134:1187 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 6 11 theme functions 1247:1255 arg1 understanding 1212:1224 our understanding 1208:1224 our understanding of core fucosylation functions in various diseases 1208:1275 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 0 12 theme spectrometry 107:118 arg1 analysis 120:127 mass spectrometry analysis 102:127 mass spectrometry analysis 102:127 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 35798744 6 13 from mixtures 1180:1187 arg1 events 1152:1157 core fucosylation events 1134:1157 core fucosylation events from complex protein mixtures 1134:1187 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 6 13 from mixtures 1180:1187 arg1 characterization 1114:1129 quantitative characterization 1101:1129 quantitative characterization 1101:1129 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 3 14 gly glycoproteins 589:601 arg1 glycoproteins 589:601 glycoproteins 589:601 glycoproteins 589:601 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 6 15 from understanding 1212:1224 arg1 diseases 1268:1275 various diseases 1260:1275 various diseases 1260:1275 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 0 16 theme mass 102:105 arg1 analysis 120:127 mass spectrometry analysis 102:127 mass spectrometry analysis 102:127 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 35798744 6 17 theme STAGE 1080:1084 arg1 method 1086:1091 our STAGE method 1076:1091 our STAGE method 1076:1091 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 4 18 theme F 657:657 arg1 treatment 659:667 PNGase F treatment 650:667 PNGase F treatment 650:667 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 5 19 theme glycoproteins 869:881 arg1 fucosylation 853:864 site specific core fucosylation 834:864 site specific core fucosylation of glycoproteins 834:881 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 2 20 theme N-linked 392:399 arg1 glycosylation 401:413 N-linked glycosylation 392:413 N-linked glycosylation 392:413 However, quantitative characterization of core fucosylation remains challenging due to the complexity and heterogeneity of N-linked glycosylation. 35798744 5 21 theme pancreatic 923:932 arg1 adenocarcinoma 941:954 pancreatic ductal adenocarcinoma 923:954 pancreatic ductal adenocarcinoma 923:954 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 0 22 gly glycopeptides 84:96 arg2 glycopeptides 84:96 intact glycopeptides 77:96 intact glycopeptides 77:96 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 35798744 3 23 theme intact 501:506 arg1 glycopeptides 508:520 intact glycopeptides 501:520 intact glycopeptides 501:520 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 0 24 theme analysis 120:127 arg1 treatments 63:72 sequential enzymatic treatments 42:72 sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis 42:127 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 35798744 1 25 attach linked 183:188 arg1 functions 197:205 the functions 193:205 the functions of glycoproteins in physiological and pathological processes 193:266 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 1 25 attach linked 183:188 arg2 fucosylation 135:146 Core fucosylation 130:146 Core fucosylation of N-linked glycoproteins 130:172 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 1 26 gly glycoproteins 210:222 arg1 glycoproteins 210:222 glycoproteins 210:222 glycoproteins 210:222 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 2 27 theme core 311:314 arg1 fucosylation 316:327 core fucosylation 311:327 core fucosylation 311:327 However, quantitative characterization of core fucosylation remains challenging due to the complexity and heterogeneity of N-linked glycosylation. 35798744 3 28 theme glycopeptides 508:520 arg1 treatment 488:496 sequential treatment 477:496 sequential treatment of intact glycopeptides with enzymes (STAGE) 477:541 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 5 29 theme specific 839:846 arg1 fucosylation 853:864 site specific core fucosylation 834:864 site specific core fucosylation of glycoproteins 834:881 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 1 30 link N-linked 151:158 arg1 glycoproteins 160:172 N-linked glycoproteins 151:172 N-linked glycoproteins 151:172 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 4 31 theme core 742:745 arg1 glycans 768:774 core fucosylated N-linked glycans 742:774 core fucosylated N-linked glycans 742:774 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 3 32 theme spectrometry-based 438:455 arg1 method 457:462 a mass spectrometry-based method 431:462 a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins 431:601 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 4 33 theme Endo 630:633 arg1 F3 635:636 Endo F3 630:636 Endo F3 followed by PNGase F treatment 630:667 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 5 34 theme human 888:892 arg1 carcinoma 909:917 human hepatocellular carcinoma 888:917 human hepatocellular carcinoma 888:917 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 6 35 theme quantitative 1101:1112 arg1 characterization 1114:1129 quantitative characterization 1101:1129 quantitative characterization 1101:1129 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 0 36 theme fucosylation 25:36 arg1 Characterization 0:15 Characterization 0:15 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 0:128 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 35798744 5 37 gly glycoproteins 869:881 arg1 glycoproteins 869:881 glycoproteins 869:881 glycoproteins 869:881 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 1 38 gly fucosylation 135:146 arg1 glycoproteins 160:172 N-linked glycoproteins 151:172 N-linked glycoproteins 151:172 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 3 39 gly fucosylation 573:584 arg1 glycoproteins 589:601 glycoproteins 589:601 glycoproteins 589:601 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 4 40 link N-linked 759:766 arg1 glycans 768:774 core fucosylated N-linked glycans 742:774 core fucosylated N-linked glycans 742:774 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 1 41 theme glycoproteins 210:222 arg1 functions 197:205 the functions 193:205 the functions of glycoproteins in physiological and pathological processes 193:266 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 0 42 theme core 20:23 arg1 fucosylation 25:36 core fucosylation 20:36 core fucosylation 20:36 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 35798744 2 43 theme fucosylation 316:327 arg1 characterization 291:306 quantitative characterization 278:306 quantitative characterization of core fucosylation 278:327 However, quantitative characterization of core fucosylation remains challenging due to the complexity and heterogeneity of N-linked glycosylation. 35798744 6 44 theme various 1260:1266 arg1 diseases 1268:1275 various diseases 1260:1275 various diseases 1260:1275 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 4 45 theme N-linked 759:766 arg1 glycans 768:774 core fucosylated N-linked glycans 742:774 core fucosylated N-linked glycans 742:774 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 0 46 theme sequential 42:51 arg1 treatments 63:72 sequential enzymatic treatments 42:72 sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis 42:127 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 35798744 5 47 theme core 1005:1008 arg1 glycosites 1022:1031 1130 and 782 core fucosylated glycosites 992:1031 1130 and 782 core fucosylated glycosites 992:1031 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 5 48 gly glycosites 1022:1031 arg2 glycosites 1022:1031 1130 and 782 core fucosylated glycosites 992:1031 1130 and 782 core fucosylated glycosites 992:1031 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 5 49 theme ductal 934:939 arg1 adenocarcinoma 941:954 pancreatic ductal adenocarcinoma 923:954 pancreatic ductal adenocarcinoma 923:954 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 5 50 theme STAGE 794:798 arg1 method 800:805 the STAGE method 790:805 the STAGE method 790:805 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 4 51 mod modified 730:737 arg3 glycans 768:774 core fucosylated N-linked glycans 742:774 core fucosylated N-linked glycans 742:774 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 4 51 mod modified 730:737 arg1 glycosites 701:710 glycosites 701:710 glycosites that are formerly modified by core fucosylated N-linked glycans 701:774 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 1 52 theme physiological 227:239 arg1 processes 258:266 physiological and pathological processes 227:266 physiological and pathological processes 227:266 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 3 53 theme sequential 477:486 arg1 treatment 488:496 sequential treatment 477:496 sequential treatment of intact glycopeptides with enzymes (STAGE) 477:541 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 5 54 gly fucosylated 1010:1020 arg1 glycosites 1022:1031 1130 and 782 core fucosylated glycosites 992:1031 1130 and 782 core fucosylated glycosites 992:1031 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 5 55 theme hepatocellular 894:907 arg1 carcinoma 909:917 human hepatocellular carcinoma 888:917 human hepatocellular carcinoma 888:917 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 6 56 theme events 1152:1157 arg1 characterization 1114:1129 quantitative characterization 1101:1129 quantitative characterization 1101:1129 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 3 57 with treatment 488:496 arg1 enzymes 527:533 enzymes 527:533 enzymes (STAGE) 527:541 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 3 57 with treatment 488:496 arg1 STAGE 536:540 STAGE 536:540 STAGE 536:540 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 6 58 theme fucosylation 1234:1245 arg1 functions 1247:1255 core fucosylation functions 1229:1255 core fucosylation functions in various diseases 1229:1275 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 1 59 theme Core 130:133 arg1 fucosylation 135:146 Core fucosylation 130:146 Core fucosylation of N-linked glycoproteins 130:172 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 0 60 theme enzymatic 53:61 arg1 treatments 63:72 sequential enzymatic treatments 42:72 sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis 42:127 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 35798744 1 61 gly glycoproteins 160:172 arg1 glycoproteins 160:172 N-linked glycoproteins 151:172 N-linked glycoproteins 151:172 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 4 62 gly glycosites 701:710 arg2 glycosites 701:710 glycosites 701:710 glycosites that are formerly modified by core fucosylated N-linked glycans 701:774 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 3 63 theme site-specific 554:566 arg1 fucosylation 573:584 site-specific core fucosylation 554:584 site-specific core fucosylation of glycoproteins 554:601 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 4 64 theme STAGE 608:612 arg1 method 614:619 The STAGE method 604:619 The STAGE method 604:619 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 5 65 gly fucosylation 853:864 arg1 glycoproteins 869:881 glycoproteins 869:881 glycoproteins 869:881 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 3 66 gly glycopeptides 508:520 arg2 glycopeptides 508:520 intact glycopeptides 501:520 intact glycopeptides 501:520 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 4 67 theme fucosylated 747:757 arg1 glycans 768:774 core fucosylated N-linked glycans 742:774 core fucosylated N-linked glycans 742:774 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35798744 5 68 theme fucosylated 1010:1020 arg1 glycosites 1022:1031 1130 and 782 core fucosylated glycosites 992:1031 1130 and 782 core fucosylated glycosites 992:1031 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 6 69 theme core 1229:1232 arg1 fucosylation 1234:1245 core fucosylation 1229:1245 core fucosylation functions in various diseases 1229:1275 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 1 70 theme pathological 245:256 arg1 processes 258:266 physiological and pathological processes 227:266 physiological and pathological processes 227:266 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 2 71 gly heterogeneity 375:387 arg1 glycosylation 401:413 N-linked glycosylation 392:413 N-linked glycosylation 392:413 However, quantitative characterization of core fucosylation remains challenging due to the complexity and heterogeneity of N-linked glycosylation. 35798744 5 72 theme core 848:851 arg1 fucosylation 853:864 site specific core fucosylation 834:864 site specific core fucosylation of glycoproteins 834:881 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 1 73 from functions 197:205 arg1 processes 258:266 physiological and pathological processes 227:266 physiological and pathological processes 227:266 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 1 74 theme N-linked 151:158 arg1 glycoproteins 160:172 N-linked glycoproteins 151:172 N-linked glycoproteins 151:172 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 6 75 from diseases 1268:1275 arg1 understanding 1212:1224 our understanding 1208:1224 our understanding of core fucosylation functions in various diseases 1208:1275 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 5 76 theme glycosites 1022:1031 arg1 identification 974:987 the identification 970:987 the identification of 1130 and 782 core fucosylated glycosites, respectively 970:1045 We benchmark the STAGE method and use it to characterize site specific core fucosylation of glycoproteins from human hepatocellular carcinoma and pancreatic ductal adenocarcinoma, resulting in the identification of 1130 and 782 core fucosylated glycosites, respectively. 35798744 0 77 theme intact 77:82 arg1 glycopeptides 84:96 intact glycopeptides 77:96 intact glycopeptides 77:96 Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. 35798744 2 78 theme quantitative 278:289 arg1 characterization 291:306 quantitative characterization 278:306 quantitative characterization of core fucosylation 278:327 However, quantitative characterization of core fucosylation remains challenging due to the complexity and heterogeneity of N-linked glycosylation. 35798744 6 79 theme protein 1172:1178 arg1 mixtures 1180:1187 complex protein mixtures 1164:1187 complex protein mixtures 1164:1187 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 1 80 theme glycoproteins 160:172 arg1 fucosylation 135:146 Core fucosylation 130:146 Core fucosylation of N-linked glycoproteins 130:172 Core fucosylation of N-linked glycoproteins has been linked to the functions of glycoproteins in physiological and pathological processes. 35798744 6 81 theme fucosylation 1139:1150 arg1 events 1152:1157 core fucosylation events 1134:1157 core fucosylation events from complex protein mixtures 1134:1187 These results indicate that our STAGE method enables quantitative characterization of core fucosylation events from complex protein mixtures, which may benefit our understanding of core fucosylation functions in various diseases. 35798744 3 82 theme glycoproteins 589:601 arg1 fucosylation 573:584 site-specific core fucosylation 554:584 site-specific core fucosylation of glycoproteins 554:601 Here we report a mass spectrometry-based method that employs sequential treatment of intact glycopeptides with enzymes (STAGE) to analyze site-specific core fucosylation of glycoproteins. 35798744 4 83 theme mass 681:684 arg1 signatures 686:695 mass signatures 681:695 mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans 681:774 The STAGE method utilizes Endo F3 followed by PNGase F treatment to generate mass signatures for glycosites that are formerly modified by core fucosylated N-linked glycans. 35687069 5 0 theme kefir 703:707 arg1 grains 709:714 kefir grains 703:714 kefir grains 703:714 Furthermore, they were highly related to the microbiota in kefir grains. 35687069 1 1 theme nitrogen 131:138 arg1 source 140:145 a nitrogen source 129:145 a nitrogen source for microorganisms 129:164 Proteins not only serve as a nitrogen source for microorganisms but are the main skeleton of kefir grains. 35687069 2 2 from proteins 255:262 arg1 grains 292:297 three kefir grains 280:297 three kefir grains from China, Germany, and the United States 280:340 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 2 from proteins 255:262 arg1 States 335:340 the United States 324:340 the United States 324:340 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 2 from proteins 255:262 arg1 Germany 311:317 Germany 311:317 Germany 311:317 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 2 from proteins 255:262 arg1 China 304:308 China 304:308 China 304:308 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 6 3 theme peptides 767:774 arg1 number 733:738 a number 731:738 a number of hydrophilic/hydrophobic peptides that were hydrolyzed by extracellular proteases 731:822 Additionally, a number of hydrophilic/hydrophobic peptides that were hydrolyzed by extracellular proteases were found from kefir grains. 35687069 4 4 theme grains 636:641 arg1 stability 619:627 the morphological stability 601:627 the morphological stability of the grains 601:641 These proteins could form aggregates through a covalent interaction with polysaccharides to maintain the morphological stability of the grains. 35687069 0 5 theme Goat 91:94 arg1 Milk 96:99 Goat Milk 91:99 Goat Milk 91:99 Differences in Protein Profiles of Kefir Grains from Different Origins When Subcultured in Goat Milk. 35687069 7 6 theme Lactobacillus 899:911 arg1 sp 913:914 Lactobacillus sp 899:914 Lactobacillus sp 899:914 A correlation may exist between peptides and Lactobacillus sp. 35687069 6 7 theme hydrophilic/hydrophobic 743:765 arg1 peptides 767:774 hydrophilic/hydrophobic peptides 743:774 hydrophilic/hydrophobic peptides that were hydrolyzed by extracellular proteases 743:822 Additionally, a number of hydrophilic/hydrophobic peptides that were hydrolyzed by extracellular proteases were found from kefir grains. 35687069 2 8 from peptides 268:275 arg1 grains 292:297 three kefir grains 280:297 three kefir grains from China, Germany, and the United States 280:340 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 8 from peptides 268:275 arg1 States 335:340 the United States 324:340 the United States 324:340 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 8 from peptides 268:275 arg1 Germany 311:317 Germany 311:317 Germany 311:317 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 8 from peptides 268:275 arg1 China 304:308 China 304:308 China 304:308 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 10 9 theme grains 1143:1148 arg1 composition 1122:1132 the protein and peptide composition 1098:1132 composition 1122:1132 The results indicated that goat milk as a substrate affects the protein and peptide composition of kefir grains. 35687069 10 10 theme kefir 1137:1141 arg1 grains 1143:1148 kefir grains 1137:1148 kefir grains 1137:1148 The results indicated that goat milk as a substrate affects the protein and peptide composition of kefir grains. 35687069 3 11 from milk 467:470 arg1 αs2-casein 432:441 αs2-casein 432:441 αs2-casein 432:441 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 3 11 from milk 467:470 arg1 β-casein 448:455 β-casein 448:455 β-casein 448:455 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 3 11 from milk 467:470 arg1 αs1-casein 420:429 αs1-casein 420:429 αs1-casein 420:429 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 1 12 dep Proteins 102:109 arg1 only 115:118 only 115:118 only 115:118 Proteins not only serve as a nitrogen source for microorganisms but are the main skeleton of kefir grains. 35687069 9 13 theme kefir 1024:1028 arg1 grains 1030:1035 these kefir grains 1018:1035 these kefir grains 1018:1035 Bioactive peptides, including DKIHPF, LGPVRGPFP, and QEPVLGPVRGPFP, were found from these kefir grains. 35687069 3 14 theme S-layer 372:378 arg1 protein 380:386 the S-layer protein 368:386 the S-layer protein from special Lactobacillus sp. 368:417 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 6 15 theme kefir 840:844 arg1 grains 846:851 kefir grains 840:851 kefir grains 840:851 Additionally, a number of hydrophilic/hydrophobic peptides that were hydrolyzed by extracellular proteases were found from kefir grains. 35687069 2 16 theme United 328:333 arg1 States 335:340 the United States 324:340 the United States 324:340 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 17 from China 304:308 arg1 grains 292:297 three kefir grains 280:297 three kefir grains from China, Germany, and the United States 280:340 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 17 from China 304:308 arg1 peptides 268:275 peptides 268:275 peptides 268:275 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 17 from China 304:308 arg1 proteins 255:262 proteins 255:262 proteins 255:262 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 3 18 located found 477:481 arg2 αs2-casein 432:441 αs2-casein 432:441 αs2-casein 432:441 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 3 18 located found 477:481 arg2 β-casein 448:455 β-casein 448:455 β-casein 448:455 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 3 18 located found 477:481 arg1 grains 492:497 kefir grains 486:497 kefir grains 486:497 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 3 18 located found 477:481 arg2 αs1-casein 420:429 αs1-casein 420:429 αs1-casein 420:429 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 4 19 theme morphological 605:617 arg1 stability 619:627 the morphological stability 601:627 the morphological stability of the grains 601:641 These proteins could form aggregates through a covalent interaction with polysaccharides to maintain the morphological stability of the grains. 35687069 9 20 theme Bioactive 934:942 arg1 LGPVRGPFP 972:980 LGPVRGPFP 972:980 LGPVRGPFP 972:980 Bioactive peptides, including DKIHPF, LGPVRGPFP, and QEPVLGPVRGPFP, were found from these kefir grains. 35687069 9 20 theme Bioactive 934:942 arg1 peptides 944:951 Bioactive peptides 934:951 Bioactive peptides 934:951 Bioactive peptides, including DKIHPF, LGPVRGPFP, and QEPVLGPVRGPFP, were found from these kefir grains. 35687069 9 20 theme Bioactive 934:942 arg1 DKIHPF 964:969 DKIHPF 964:969 DKIHPF 964:969 Bioactive peptides, including DKIHPF, LGPVRGPFP, and QEPVLGPVRGPFP, were found from these kefir grains. 35687069 9 20 theme Bioactive 934:942 arg1 QEPVLGPVRGPFP 987:999 QEPVLGPVRGPFP 987:999 QEPVLGPVRGPFP 987:999 Bioactive peptides, including DKIHPF, LGPVRGPFP, and QEPVLGPVRGPFP, were found from these kefir grains. 35687069 2 21 from Germany 311:317 arg1 grains 292:297 three kefir grains 280:297 three kefir grains from China, Germany, and the United States 280:340 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 21 from Germany 311:317 arg1 peptides 268:275 peptides 268:275 peptides 268:275 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 21 from Germany 311:317 arg1 proteins 255:262 proteins 255:262 proteins 255:262 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 22 from subculturing 215:226 arg1 milk 236:239 goat milk 231:239 goat milk 231:239 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 0 23 theme Protein 15:21 arg1 Profiles 23:30 Protein Profiles 15:30 Protein Profiles of Kefir Grains from Different Origins 15:69 Differences in Protein Profiles of Kefir Grains from Different Origins When Subcultured in Goat Milk. 35687069 3 24 theme goat 462:465 arg1 milk 467:470 goat milk 462:470 goat milk 462:470 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 3 25 theme kefir 486:490 arg1 grains 492:497 kefir grains 486:497 kefir grains 486:497 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 1 26 theme main 178:181 arg1 skeleton 183:190 the main skeleton 174:190 the main skeleton of kefir grains 174:206 Proteins not only serve as a nitrogen source for microorganisms but are the main skeleton of kefir grains. 35687069 0 27 theme Kefir 35:39 arg1 Grains 41:46 Kefir Grains 35:46 Kefir Grains from Different Origins 35:69 Differences in Protein Profiles of Kefir Grains from Different Origins When Subcultured in Goat Milk. 35687069 10 28 theme goat 1065:1068 arg1 milk 1070:1073 goat milk 1065:1073 goat milk as a substrate 1065:1088 The results indicated that goat milk as a substrate affects the protein and peptide composition of kefir grains. 35687069 10 29 theme protein 1102:1108 arg1 composition 1122:1132 the protein and peptide composition 1098:1132 composition 1122:1132 The results indicated that goat milk as a substrate affects the protein and peptide composition of kefir grains. 35687069 0 30 from Origins 63:69 arg1 Profiles 23:30 Protein Profiles 15:30 Protein Profiles of Kefir Grains from Different Origins 15:69 Differences in Protein Profiles of Kefir Grains from Different Origins When Subcultured in Goat Milk. 35687069 0 30 from Origins 63:69 arg1 Grains 41:46 Kefir Grains 35:46 Kefir Grains from Different Origins 35:69 Differences in Protein Profiles of Kefir Grains from Different Origins When Subcultured in Goat Milk. 35687069 10 31 theme peptide 1114:1120 arg1 composition 1122:1132 the protein and peptide composition 1098:1132 composition 1122:1132 The results indicated that goat milk as a substrate affects the protein and peptide composition of kefir grains. 35687069 6 32 theme extracellular 800:812 arg1 proteases 814:822 extracellular proteases 800:822 extracellular proteases 800:822 Additionally, a number of hydrophilic/hydrophobic peptides that were hydrolyzed by extracellular proteases were found from kefir grains. 35687069 0 33 theme Grains 41:46 arg1 Profiles 23:30 Protein Profiles 15:30 Protein Profiles of Kefir Grains from Different Origins 15:69 Differences in Protein Profiles of Kefir Grains from Different Origins When Subcultured in Goat Milk. 35687069 2 34 from States 335:340 arg1 grains 292:297 three kefir grains 280:297 three kefir grains from China, Germany, and the United States 280:340 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 34 from States 335:340 arg1 peptides 268:275 peptides 268:275 peptides 268:275 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 2 34 from States 335:340 arg1 proteins 255:262 proteins 255:262 proteins 255:262 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 3 35 from sp. 415:417 arg1 protein 380:386 the S-layer protein 368:386 the S-layer protein from special Lactobacillus sp. 368:417 Except for the S-layer protein from special Lactobacillus sp., αs1-casein, αs2-casein, and β-casein from goat milk were found in kefir grains. 35687069 2 36 theme kefir 286:290 arg1 grains 292:297 three kefir grains 280:297 three kefir grains from China, Germany, and the United States 280:340 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 1 37 theme kefir 195:199 arg1 grains 201:206 kefir grains 195:206 kefir grains 195:206 Proteins not only serve as a nitrogen source for microorganisms but are the main skeleton of kefir grains. 35687069 5 38 from microbiota 689:698 arg1 grains 709:714 kefir grains 703:714 kefir grains 703:714 Furthermore, they were highly related to the microbiota in kefir grains. 35687069 2 39 theme goat 231:234 arg1 milk 236:239 goat milk 231:239 goat milk 231:239 After subculturing in goat milk for 4 months, proteins and peptides in three kefir grains from China, Germany, and the United States were analyzed. 35687069 1 40 theme grains 201:206 arg1 skeleton 183:190 the main skeleton 174:190 the main skeleton of kefir grains 174:206 Proteins not only serve as a nitrogen source for microorganisms but are the main skeleton of kefir grains. 35687069 4 41 with interaction 556:566 arg1 polysaccharides 573:587 polysaccharides 573:587 polysaccharides 573:587 These proteins could form aggregates through a covalent interaction with polysaccharides to maintain the morphological stability of the grains. 35687069 4 42 theme covalent 547:554 arg1 interaction 556:566 a covalent interaction 545:566 a covalent interaction with polysaccharides to maintain the morphological stability of the grains 545:641 These proteins could form aggregates through a covalent interaction with polysaccharides to maintain the morphological stability of the grains. 35687069 0 43 theme Different 53:61 arg1 Origins 63:69 Different Origins 53:69 Different Origins 53:69 Differences in Protein Profiles of Kefir Grains from Different Origins When Subcultured in Goat Milk. 35687069 0 44 from Profiles 23:30 arg1 Origins 63:69 Different Origins 53:69 Different Origins 53:69 Differences in Protein Profiles of Kefir Grains from Different Origins When Subcultured in Goat Milk. 35687069 8 45 theme kefir 920:924 arg1 grains 926:931 kefir grains 920:931 kefir grains 920:931 in kefir grains. 35489263 0 0 theme products 76:83 arg1 formation 45:53 the formation 41:53 the formation of Maillard reaction products in different cereals 41:104 Effects of sprouting and fermentation on the formation of Maillard reaction products in different cereals heated as wholemeal. 35489263 2 1 theme sourdough 468:476 arg1 heating 447:453 heating 447:453 heating of yeast and sourdough fermented native and sprouted wholemeals 447:517 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 2 2 theme compounds 340:348 arg1 formation 271:279 The formation 267:279 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates 267:365 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 0 3 theme reaction 67:74 arg1 products 76:83 Maillard reaction products 58:83 Maillard reaction products 58:83 Effects of sprouting and fermentation on the formation of Maillard reaction products in different cereals heated as wholemeal. 35489263 2 4 theme α-dicarbonyl 327:338 arg1 compounds 340:348 α-dicarbonyl compounds 327:348 α-dicarbonyl compounds as intermediates 327:365 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 0 5 theme different 88:96 arg1 cereals 98:104 different cereals 88:104 different cereals 88:104 Effects of sprouting and fermentation on the formation of Maillard reaction products in different cereals heated as wholemeal. 35489263 0 6 from Effects 0:6 arg1 formation 45:53 the formation 41:53 the formation of Maillard reaction products in different cereals 41:104 Effects of sprouting and fermentation on the formation of Maillard reaction products in different cereals heated as wholemeal. 35489263 2 7 dep yeast 458:462 arg1 wholemeals 508:517 fermented native and sprouted wholemeals 478:517 fermented native and sprouted wholemeals 478:517 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 3 8 theme MR 565:566 arg1 products 568:575 all MR products 561:575 all MR products 561:575 Sprouting increased the concentration of all MR products because of an increase in reducing sugar concentrations. 35489263 0 9 from formation 45:53 arg1 cereals 98:104 different cereals 88:104 different cereals 88:104 Effects of sprouting and fermentation on the formation of Maillard reaction products in different cereals heated as wholemeal. 35489263 7 10 theme bound 1147:1151 arg1 lysine 1153:1158 bound lysine 1147:1158 bound lysine 1147:1158 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 1 11 theme grain 250:254 arg1 sprouting 256:264 grain sprouting 250:264 grain sprouting 250:264 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 2 12 theme sprouted 499:506 arg1 wholemeals 508:517 fermented native and sprouted wholemeals 478:517 fermented native and sprouted wholemeals 478:517 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 2 13 theme sprouted 408:415 arg1 wholemeals 417:426 native and sprouted wholemeals 397:426 native and sprouted wholemeals 397:426 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 1 14 theme reducing 164:171 arg1 sugars 173:178 reducing sugars 164:178 reducing sugars 164:178 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 1 15 theme sugars 173:178 arg1 composition 149:159 composition 149:159 composition 149:159 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 1 15 theme sugars 173:178 arg1 concentration 131:143 concentration 131:143 concentration 131:143 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 5 16 theme low 830:832 arg1 pH 834:835 the low pH 826:835 the low pH 826:835 Sourdough fermentation unexpectedly increased furosine because the low pH caused glucose release from polysaccharides. 35489263 7 17 theme amino 1117:1121 arg1 acids 1123:1127 total free amino acids 1106:1127 total free amino acids that compete with bound lysine to react with reducing sugars 1106:1188 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 2 18 theme native 488:493 arg1 wholemeals 508:517 fermented native and sprouted wholemeals 478:517 fermented native and sprouted wholemeals 478:517 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 2 19 theme advanced 294:301 arg1 products 313:320 early and advanced glycation products 284:320 early and advanced glycation products 284:320 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 7 20 from MR 1027:1028 arg1 wholemeals 1052:1061 sprouted/fermented wholemeals 1033:1061 sprouted/fermented wholemeals 1033:1061 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 7 21 theme acids 1123:1127 arg1 acids 1123:1127 total free amino acids 1106:1127 total free amino acids that compete with bound lysine to react with reducing sugars 1106:1188 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 7 21 theme acids 1123:1127 arg1 amount 1096:1101 the increased amount 1082:1101 the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars 1082:1188 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 7 21 theme acids 1123:1127 arg1 factor 1006:1011 Another factor 998:1011 Another factor affecting the MR in sprouted/fermented wholemeals 998:1061 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 3 22 theme products 568:575 arg1 concentration 544:556 the concentration 540:556 the concentration of all MR products 540:575 Sprouting increased the concentration of all MR products because of an increase in reducing sugar concentrations. 35489263 1 23 theme free 184:187 arg1 acids 195:199 free amino acids 184:199 free amino acids 184:199 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 7 24 theme total 1106:1110 arg1 acids 1123:1127 total free amino acids 1106:1127 total free amino acids that compete with bound lysine to react with reducing sugars 1106:1188 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 1 25 dep concentration 131:143 arg1 The 127:129 The 127:129 The 127:129 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 1 26 theme amino 189:193 arg1 acids 195:199 free amino acids 184:199 free amino acids 184:199 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 0 27 theme sprouting 11:19 arg1 Effects 0:6 Effects 0:6 Effects of sprouting and fermentation on the formation of Maillard reaction products in different cereals 0:104 Effects of sprouting and fermentation on the formation of Maillard reaction products in different cereals heated as wholemeal. 35489263 7 28 theme free 1112:1115 arg1 acids 1123:1127 total free amino acids 1106:1127 total free amino acids that compete with bound lysine to react with reducing sugars 1106:1188 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 4 29 theme furosine 739:746 arg1 concentration 748:760 the furosine concentration 735:760 the furosine concentration 735:760 Although reducing sugars were lowered due to their consumption by yeasts, fermentation did not lower the furosine concentration. 35489263 1 30 theme acids 195:199 arg1 composition 149:159 composition 149:159 composition 149:159 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 1 30 theme acids 195:199 arg1 concentration 131:143 concentration 131:143 concentration 131:143 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 2 31 theme yeast 458:462 arg1 heating 447:453 heating 447:453 heating of yeast and sourdough fermented native and sprouted wholemeals 447:517 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 4 32 theme reducing 643:650 arg1 sugars 652:657 reducing sugars 643:657 reducing sugars 643:657 Although reducing sugars were lowered due to their consumption by yeasts, fermentation did not lower the furosine concentration. 35489263 3 33 from increase 591:598 arg1 concentrations 618:631 reducing sugar concentrations 603:631 reducing sugar concentrations 603:631 Sprouting increased the concentration of all MR products because of an increase in reducing sugar concentrations. 35489263 0 34 theme fermentation 25:36 arg1 Effects 0:6 Effects 0:6 Effects of sprouting and fermentation on the formation of Maillard reaction products in different cereals 0:104 Effects of sprouting and fermentation on the formation of Maillard reaction products in different cereals heated as wholemeal. 35489263 6 35 theme sourdough 974:982 arg1 fermentation 984:995 sourdough fermentation 974:995 sourdough fermentation 974:995 Glyoxal, methylglyoxal and diacetyl were found to be formed as metabolites during yeast and sourdough fermentation. 35489263 5 36 from polysaccharides 865:879 arg1 release 852:858 glucose release 844:858 glucose release from polysaccharides 844:879 Sourdough fermentation unexpectedly increased furosine because the low pH caused glucose release from polysaccharides. 35489263 1 37 theme Maillard 204:211 arg1 MR 223:224 MR 223:224 MR 223:224 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 1 37 theme Maillard 204:211 arg1 reaction 213:220 Maillard reaction 204:220 Maillard reaction (MR) precursors 204:236 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 5 38 theme Sourdough 763:771 arg1 fermentation 773:784 Sourdough fermentation 763:784 Sourdough fermentation 763:784 Sourdough fermentation unexpectedly increased furosine because the low pH caused glucose release from polysaccharides. 35489263 7 39 theme increased 1086:1094 arg1 acids 1123:1127 total free amino acids 1106:1127 total free amino acids that compete with bound lysine to react with reducing sugars 1106:1188 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 7 39 theme increased 1086:1094 arg1 amount 1096:1101 the increased amount 1082:1101 the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars 1082:1188 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 7 39 theme increased 1086:1094 arg1 factor 1006:1011 Another factor 998:1011 Another factor affecting the MR in sprouted/fermented wholemeals 998:1061 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 7 40 theme sprouted/fermented 1033:1050 arg1 wholemeals 1052:1061 sprouted/fermented wholemeals 1033:1061 sprouted/fermented wholemeals 1033:1061 Another factor affecting the MR in sprouted/fermented wholemeals was revealed to be the increased amount of total free amino acids that compete with bound lysine to react with reducing sugars. 35489263 3 41 theme sugar 612:616 arg1 concentrations 618:631 reducing sugar concentrations 603:631 reducing sugar concentrations 603:631 Sprouting increased the concentration of all MR products because of an increase in reducing sugar concentrations. 35489263 2 42 theme products 313:320 arg1 formation 271:279 The formation 267:279 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates 267:365 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 2 43 theme early 284:288 arg1 products 313:320 early and advanced glycation products 284:320 early and advanced glycation products 284:320 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 1 44 theme reaction 213:220 arg1 precursors 227:236 Maillard reaction (MR) precursors 204:236 Maillard reaction (MR) precursors 204:236 The concentration and composition of reducing sugars and free amino acids as Maillard reaction (MR) precursors change with grain sprouting. 35489263 5 45 theme glucose 844:850 arg1 release 852:858 glucose release 844:858 glucose release from polysaccharides 844:879 Sourdough fermentation unexpectedly increased furosine because the low pH caused glucose release from polysaccharides. 35489263 2 46 theme glycation 303:311 arg1 products 313:320 early and advanced glycation products 284:320 early and advanced glycation products 284:320 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 0 47 theme Maillard 58:65 arg1 products 76:83 Maillard reaction products 58:83 Maillard reaction products 58:83 Effects of sprouting and fermentation on the formation of Maillard reaction products in different cereals heated as wholemeal. 35489263 2 48 theme native 397:402 arg1 wholemeals 417:426 native and sprouted wholemeals 397:426 native and sprouted wholemeals 397:426 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 2 49 theme fermented 478:486 arg1 wholemeals 508:517 fermented native and sprouted wholemeals 478:517 fermented native and sprouted wholemeals 478:517 The formation of early and advanced glycation products, and α-dicarbonyl compounds as intermediates were monitored during heating native and sprouted wholemeals, as well as during heating of yeast and sourdough fermented native and sprouted wholemeals. 35489263 3 50 theme reducing 603:610 arg1 concentrations 618:631 reducing sugar concentrations 603:631 reducing sugar concentrations 603:631 Sprouting increased the concentration of all MR products because of an increase in reducing sugar concentrations. 35741411 5 0 theme green 699:703 arg1 bacteria 710:717 green snow bacteria 699:717 green snow bacteria 699:717 The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) was smaller. 35741411 9 1 theme whole 1132:1136 arg1 profile 1147:1153 the whole chemical profile 1128:1153 the whole chemical profile 1128:1153 Growth on different media resulted in the change of the whole chemical profile, where lipids showed to be more affected than proteins and polysaccharides. 35741411 2 2 theme green 394:398 arg1 snow 400:403 green snow 394:403 green snow 394:403 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 5 3 theme snow 705:708 arg1 bacteria 710:717 green snow bacteria 699:717 green snow bacteria 699:717 The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) was smaller. 35741411 9 4 theme chemical 1138:1145 arg1 profile 1147:1153 the whole chemical profile 1128:1153 the whole chemical profile 1128:1153 Growth on different media resulted in the change of the whole chemical profile, where lipids showed to be more affected than proteins and polysaccharides. 35741411 1 5 theme main 190:193 arg1 parameters 195:204 the main parameters 186:204 the main parameters influencing green snow microbiome 186:238 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 1 5 theme main 190:193 arg1 fluctuations 144:155 Temperature fluctuations 132:155 Temperature fluctuations 132:155 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 1 5 theme main 190:193 arg1 composition 170:180 nutrient composition 161:180 nutrient composition 161:180 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 0 6 theme FTIR 113:116 arg1 Spectroscopy 118:129 High-Throughput FTIR Spectroscopy 97:129 High-Throughput FTIR Spectroscopy 97:129 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria Probed by High-Throughput FTIR Spectroscopy. 35741411 7 7 theme mixed 927:931 arg1 regions 942:948 Lipid and mixed spectral regions 917:948 regions 942:948 Lipid and mixed spectral regions showed to be phylogeny related. 35741411 0 8 theme High-Throughput 97:111 arg1 Spectroscopy 118:129 High-Throughput FTIR Spectroscopy 97:129 High-Throughput FTIR Spectroscopy 97:129 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria Probed by High-Throughput FTIR Spectroscopy. 35741411 10 9 theme nutrient 1264:1271 arg1 composition 1273:1283 nutrient composition 1264:1283 nutrient composition 1264:1283 Correlation analysis showed that nutrient composition is clearly strongly influencing chemical changes in the cells, followed by temperature. 35741411 2 10 attach isolated 380:387 arg1 snow 400:403 green snow 394:403 green snow 394:403 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 2 10 attach isolated 380:387 arg2 bacteria 371:378 bacteria 371:378 bacteria isolated from green snow 371:403 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 7 11 theme Lipid 917:921 arg1 regions 942:948 Lipid and mixed spectral regions 917:948 regions 942:948 Lipid and mixed spectral regions showed to be phylogeny related. 35741411 2 12 theme conditions 313:322 arg1 influence 275:283 the influence 271:283 the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow 271:403 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 3 13 theme high-throughput 464:478 arg1 spectroscopy 485:496 high-throughput FTIR spectroscopy 464:496 high-throughput FTIR spectroscopy combined with multivariate data analysis 464:537 Chemical profiling of the green snow bacteria was done by high-throughput FTIR spectroscopy combined with multivariate data analysis. 35741411 3 14 theme snow 438:441 arg1 bacteria 443:450 the green snow bacteria 428:450 the green snow bacteria 428:450 Chemical profiling of the green snow bacteria was done by high-throughput FTIR spectroscopy combined with multivariate data analysis. 35741411 5 15 theme optimal 775:781 arg1 temperature 783:793 optimal temperature 775:793 optimal temperature (18 °C) 775:801 The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) was smaller. 35741411 5 15 theme optimal 775:781 arg1 °C 799:800 18 °C 796:800 18 °C 796:800 The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) was smaller. 35741411 2 16 theme nutrient 304:311 arg1 conditions 313:322 nutrient conditions 304:322 nutrient conditions 304:322 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 3 17 theme FTIR 480:483 arg1 spectroscopy 485:496 high-throughput FTIR spectroscopy 464:496 high-throughput FTIR spectroscopy combined with multivariate data analysis 464:537 Chemical profiling of the green snow bacteria was done by high-throughput FTIR spectroscopy combined with multivariate data analysis. 35741411 5 18 theme colonies 686:693 arg1 size 678:681 The size 674:681 The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) 674:801 The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) was smaller. 35741411 5 18 theme colonies 686:693 arg1 smaller 807:813 smaller 807:813 smaller 807:813 The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) was smaller. 35741411 2 19 theme chemical 351:358 arg1 profile 360:366 cellular chemical profile 342:366 cellular chemical profile 342:366 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 1 20 theme green 218:222 arg1 microbiome 229:238 green snow microbiome 218:238 green snow microbiome 218:238 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 0 21 theme Temperature- 0:11 arg1 Changes 46:52 Temperature- and Nutrients-Induced Phenotypic Changes 0:52 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria 0:85 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria Probed by High-Throughput FTIR Spectroscopy. 35741411 2 22 theme cellular 342:349 arg1 profile 360:366 cellular chemical profile 342:366 cellular chemical profile 342:366 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 1 23 theme snow 224:227 arg1 microbiome 229:238 green snow microbiome 218:238 green snow microbiome 218:238 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 0 24 theme Phenotypic 35:44 arg1 Changes 46:52 Temperature- and Nutrients-Induced Phenotypic Changes 0:52 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria 0:85 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria Probed by High-Throughput FTIR Spectroscopy. 35741411 4 25 theme growth 610:615 arg1 ability 617:623 growth ability 610:623 growth ability 610:623 We showed that temperature and nutrients fluctuations strongly affect growth ability and chemical profile of the green snow bacteria. 35741411 2 26 from influence 275:283 arg1 profile 360:366 cellular chemical profile 342:366 cellular chemical profile 342:366 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 2 26 from influence 275:283 arg1 growth 331:336 growth 331:336 growth 331:336 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 0 27 theme Nutrients-Induced 17:33 arg1 Changes 46:52 Temperature- and Nutrients-Induced Phenotypic Changes 0:52 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria 0:85 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria Probed by High-Throughput FTIR Spectroscopy. 35741411 4 28 theme chemical 629:636 arg1 profile 638:644 chemical profile 629:644 chemical profile of the green snow bacteria 629:671 We showed that temperature and nutrients fluctuations strongly affect growth ability and chemical profile of the green snow bacteria. 35741411 3 29 theme multivariate 512:523 arg1 analysis 530:537 multivariate data analysis 512:537 multivariate data analysis 512:537 Chemical profiling of the green snow bacteria was done by high-throughput FTIR spectroscopy combined with multivariate data analysis. 35741411 3 30 theme bacteria 443:450 arg1 profiling 415:423 Chemical profiling 406:423 Chemical profiling of the green snow bacteria 406:450 Chemical profiling of the green snow bacteria was done by high-throughput FTIR spectroscopy combined with multivariate data analysis. 35741411 2 31 dep growth 331:336 arg1 the 327:329 the 327:329 the 327:329 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 9 32 theme different 1086:1094 arg1 media 1096:1100 different media 1086:1100 different media 1086:1100 Growth on different media resulted in the change of the whole chemical profile, where lipids showed to be more affected than proteins and polysaccharides. 35741411 8 33 theme temperature 1050:1060 arg1 fluctuations 1062:1073 the temperature fluctuations 1046:1073 the temperature fluctuations 1046:1073 FTIR fingerprinting indicates that lipids are often affected by the temperature fluctuations. 35741411 6 34 theme rich 837:840 arg1 medium 842:847 rich medium 837:847 rich medium 837:847 All isolates grew on rich medium, and only 19 isolates were able to grow on synthetic minimal media. 35741411 3 35 theme Chemical 406:413 arg1 profiling 415:423 Chemical profiling 406:423 Chemical profiling of the green snow bacteria 406:450 Chemical profiling of the green snow bacteria was done by high-throughput FTIR spectroscopy combined with multivariate data analysis. 35741411 5 36 dep higher 728:733 arg1 °C 739:740 25 °C 736:740 25 °C 736:740 The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) was smaller. 35741411 0 37 theme Green 67:71 arg1 Bacteria 78:85 Antarctic Green Snow Bacteria 57:85 Antarctic Green Snow Bacteria 57:85 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria Probed by High-Throughput FTIR Spectroscopy. 35741411 4 38 dep temperature 555:565 arg1 fluctuations 581:592 fluctuations 581:592 fluctuations 581:592 We showed that temperature and nutrients fluctuations strongly affect growth ability and chemical profile of the green snow bacteria. 35741411 5 39 dep lower 747:751 arg1 °C 756:757 4 °C and 10 °C 754:767 °C 756:757 The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) was smaller. 35741411 5 39 dep lower 747:751 arg1 °C 766:767 4 °C and 10 °C 754:767 °C 766:767 The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) was smaller. 35741411 1 40 theme Temperature 132:142 arg1 parameters 195:204 the main parameters 186:204 the main parameters influencing green snow microbiome 186:238 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 1 40 theme Temperature 132:142 arg1 fluctuations 144:155 Temperature fluctuations 132:155 Temperature fluctuations 132:155 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 1 40 theme Temperature 132:142 arg1 composition 170:180 nutrient composition 161:180 nutrient composition 161:180 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 0 41 theme Antarctic 57:65 arg1 Bacteria 78:85 Antarctic Green Snow Bacteria 57:85 Antarctic Green Snow Bacteria 57:85 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria Probed by High-Throughput FTIR Spectroscopy. 35741411 6 42 theme synthetic 892:900 arg1 media 910:914 synthetic minimal media 892:914 synthetic minimal media 892:914 All isolates grew on rich medium, and only 19 isolates were able to grow on synthetic minimal media. 35741411 9 43 from Growth 1076:1081 arg1 media 1096:1100 different media 1086:1100 different media 1086:1100 Growth on different media resulted in the change of the whole chemical profile, where lipids showed to be more affected than proteins and polysaccharides. 35741411 10 44 theme chemical 1317:1324 arg1 changes 1326:1332 chemical changes 1317:1332 chemical changes 1317:1332 Correlation analysis showed that nutrient composition is clearly strongly influencing chemical changes in the cells, followed by temperature. 35741411 2 45 theme bacteria 371:378 arg1 profile 360:366 cellular chemical profile 342:366 cellular chemical profile 342:366 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 2 45 theme bacteria 371:378 arg1 growth 331:336 growth 331:336 growth 331:336 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 9 46 theme profile 1147:1153 arg1 change 1118:1123 the change 1114:1123 the change of the whole chemical profile, where lipids showed to be more affected than proteins and polysaccharides 1114:1228 Growth on different media resulted in the change of the whole chemical profile, where lipids showed to be more affected than proteins and polysaccharides. 35741411 3 47 theme data 525:528 arg1 analysis 530:537 multivariate data analysis 512:537 multivariate data analysis 512:537 Chemical profiling of the green snow bacteria was done by high-throughput FTIR spectroscopy combined with multivariate data analysis. 35741411 4 48 theme bacteria 664:671 arg1 ability 617:623 growth ability 610:623 growth ability 610:623 We showed that temperature and nutrients fluctuations strongly affect growth ability and chemical profile of the green snow bacteria. 35741411 4 48 theme bacteria 664:671 arg1 profile 638:644 chemical profile 629:644 chemical profile of the green snow bacteria 629:671 We showed that temperature and nutrients fluctuations strongly affect growth ability and chemical profile of the green snow bacteria. 35741411 2 49 theme temperature 288:298 arg1 influence 275:283 the influence 271:283 the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow 271:403 In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. 35741411 1 50 theme nutrient 161:168 arg1 parameters 195:204 the main parameters 186:204 the main parameters influencing green snow microbiome 186:238 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 1 50 theme nutrient 161:168 arg1 fluctuations 144:155 Temperature fluctuations 132:155 Temperature fluctuations 132:155 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 1 50 theme nutrient 161:168 arg1 composition 170:180 nutrient composition 161:180 nutrient composition 161:180 Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. 35741411 4 51 theme snow 659:662 arg1 bacteria 664:671 the green snow bacteria 649:671 the green snow bacteria 649:671 We showed that temperature and nutrients fluctuations strongly affect growth ability and chemical profile of the green snow bacteria. 35741411 0 52 theme Bacteria 78:85 arg1 Changes 46:52 Temperature- and Nutrients-Induced Phenotypic Changes 0:52 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria 0:85 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria Probed by High-Throughput FTIR Spectroscopy. 35741411 8 53 theme FTIR 982:985 arg1 fingerprinting 987:1000 FTIR fingerprinting 982:1000 FTIR fingerprinting 982:1000 FTIR fingerprinting indicates that lipids are often affected by the temperature fluctuations. 35741411 0 54 theme Snow 73:76 arg1 Bacteria 78:85 Antarctic Green Snow Bacteria 57:85 Antarctic Green Snow Bacteria 57:85 Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria Probed by High-Throughput FTIR Spectroscopy. 35741411 7 55 theme spectral 933:940 arg1 regions 942:948 Lipid and mixed spectral regions 917:948 regions 942:948 Lipid and mixed spectral regions showed to be phylogeny related. 35741411 10 56 from changes 1326:1332 arg1 cells 1341:1345 the cells 1337:1345 the cells 1337:1345 Correlation analysis showed that nutrient composition is clearly strongly influencing chemical changes in the cells, followed by temperature. 35741411 10 57 theme Correlation 1231:1241 arg1 analysis 1243:1250 Correlation analysis 1231:1250 Correlation analysis 1231:1250 Correlation analysis showed that nutrient composition is clearly strongly influencing chemical changes in the cells, followed by temperature. 35741411 6 58 theme minimal 902:908 arg1 media 910:914 synthetic minimal media 892:914 synthetic minimal media 892:914 All isolates grew on rich medium, and only 19 isolates were able to grow on synthetic minimal media. 36290409 7 0 theme acetic 1416:1421 arg1 acid 1423:1426 acetic acid 1416:1426 acetic acid 1416:1426 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 8 1 theme flora 1555:1559 arg1 composition 1561:1571 the microbial diversity and flora composition 1527:1571 the microbial diversity and flora composition of the mouse gut 1527:1588 Opuntia ficus-indica anthocyanins can change the microbial diversity and flora composition of the mouse gut and promote the production of short-chain fatty acids. 36290409 6 2 theme bacteria 1191:1198 arg1 abundance 1167:1175 the relative abundance 1154:1175 the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio 1154:1237 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 8 3 theme fatty 1632:1636 arg1 acids 1638:1642 short-chain fatty acids 1620:1642 short-chain fatty acids 1620:1642 Opuntia ficus-indica anthocyanins can change the microbial diversity and flora composition of the mouse gut and promote the production of short-chain fatty acids. 36290409 6 4 theme p 860:860 arg1 < 862:864 p < 0.05 860:870 p < 0.05 860:870 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 5 theme mice 1101:1104 arg1 tract 1092:1096 the intestinal tract 1077:1096 the intestinal tract of mice 1077:1104 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 6 theme relative 1158:1165 arg1 abundance 1167:1175 the relative abundance 1154:1175 the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio 1154:1237 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 4 7 theme flame 627:631 arg1 FID 654:656 FID 654:656 FID 654:656 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 7 theme flame 627:631 arg1 detector 644:651 hydrogen flame ionization detector 618:651 hydrogen flame ionization detector (FID) 618:657 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 6 8 from diversity 784:792 arg1 mice 826:829 mice 826:829 mice 826:829 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 5 9 theme fatty 707:711 arg1 SCFAs 720:724 SCFAs 720:724 SCFAs 720:724 Microbiota and effects of short-chain fatty acids (SCFAs). 36290409 5 9 theme fatty 707:711 arg1 acids 713:717 short-chain fatty acids 695:717 short-chain fatty acids (SCFAs) 695:725 Microbiota and effects of short-chain fatty acids (SCFAs). 36290409 9 10 theme theoretical 1668:1678 arg1 basis 1680:1684 a theoretical basis 1666:1684 a theoretical basis for the use of Opuntia ficus-indica anthocyanins as dietary supplements to regulate human intestinal flora 1666:1791 The findings provide a theoretical basis for the use of Opuntia ficus-indica anthocyanins as dietary supplements to regulate human intestinal flora. 36290409 6 11 dep bacteria 1191:1198 arg1 Escherichia-Shigella 1200:1219 Escherichia-Shigella 1200:1219 Escherichia-Shigella 1200:1219 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 11 dep bacteria 1191:1198 arg1 bacteria 1191:1198 pathogenic bacteria Escherichia-Shigella and Desulfovibrio 1180:1237 pathogenic bacteria Escherichia-Shigella and Desulfovibrio 1180:1237 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 11 dep bacteria 1191:1198 arg1 Desulfovibrio 1225:1237 Desulfovibrio 1225:1237 Desulfovibrio 1225:1237 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 4 12 theme ficus-indica 482:493 arg1 anthocyanins 495:506 Opuntia ficus-indica anthocyanins 474:506 Opuntia ficus-indica anthocyanins 474:506 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 0 13 theme Short-Chain 87:97 arg1 Acid 105:108 Short-Chain Fatty Acid 87:108 Short-Chain Fatty Acid Production 87:119 Anthocyanins from Opuntia ficus-indica Modulate Gut Microbiota Composition and Improve Short-Chain Fatty Acid Production. 36290409 1 14 theme active 167:172 arg1 substances 174:183 active substances 167:183 active substances 167:183 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 14 theme active 167:172 arg1 flavonoids 208:217 flavonoids 208:217 flavonoids 208:217 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 14 theme active 167:172 arg1 polysaccharides 224:238 polysaccharides 224:238 polysaccharides 224:238 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 14 theme active 167:172 arg1 anthocyanins 194:205 anthocyanins 194:205 anthocyanins 194:205 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 6 15 theme p 953:953 arg1 < 955:957 p < 0.05 953:963 p < 0.05 953:963 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 0 16 theme Acid 105:108 arg1 Production 110:119 Short-Chain Fatty Acid Production 87:119 Short-Chain Fatty Acid Production 87:119 Anthocyanins from Opuntia ficus-indica Modulate Gut Microbiota Composition and Improve Short-Chain Fatty Acid Production. 36290409 9 17 theme Opuntia 1701:1707 arg1 anthocyanins 1722:1733 Opuntia ficus-indica anthocyanins 1701:1733 Opuntia ficus-indica anthocyanins 1701:1733 The findings provide a theoretical basis for the use of Opuntia ficus-indica anthocyanins as dietary supplements to regulate human intestinal flora. 36290409 1 18 from rich 146:149 arg1 variety 156:162 a variety 154:162 a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides 154:238 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 18 from rich 146:149 arg1 substances 174:183 active substances 167:183 active substances 167:183 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 18 from rich 146:149 arg1 flavonoids 208:217 flavonoids 208:217 flavonoids 208:217 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 18 from rich 146:149 arg1 polysaccharides 224:238 polysaccharides 224:238 polysaccharides 224:238 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 18 from rich 146:149 arg1 anthocyanins 194:205 anthocyanins 194:205 anthocyanins 194:205 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 6 19 theme Lactobacillus 1014:1026 arg1 abundances 980:989 the relative abundances 967:989 the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice 967:1104 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 9 20 theme anthocyanins 1722:1733 arg1 use 1694:1696 the use 1690:1696 the use of Opuntia ficus-indica anthocyanins as dietary supplements 1690:1756 The findings provide a theoretical basis for the use of Opuntia ficus-indica anthocyanins as dietary supplements to regulate human intestinal flora. 36290409 6 21 theme beneficial 994:1003 arg1 bacteria 1005:1012 beneficial bacteria 994:1012 beneficial bacteria Lactobacillus 994:1026 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 9 22 theme dietary 1738:1744 arg1 supplements 1746:1756 dietary supplements 1738:1756 dietary supplements 1738:1756 The findings provide a theoretical basis for the use of Opuntia ficus-indica anthocyanins as dietary supplements to regulate human intestinal flora. 36290409 4 23 theme rRNA 538:541 arg1 platform 584:591 NovaSeq 6000 platform 571:591 NovaSeq 6000 platform 571:591 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 23 theme rRNA 538:541 arg1 sequencing 559:568 rRNA high-throughput sequencing 538:568 rRNA high-throughput sequencing (NovaSeq 6000 platform) 538:592 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 7 24 theme butyric 1449:1455 arg1 acid 1457:1460 butyric acid 1449:1460 butyric acid 1449:1460 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 9 25 theme human 1770:1774 arg1 flora 1787:1791 human intestinal flora 1770:1791 human intestinal flora 1770:1791 The findings provide a theoretical basis for the use of Opuntia ficus-indica anthocyanins as dietary supplements to regulate human intestinal flora. 36290409 8 26 theme Opuntia 1482:1488 arg1 anthocyanins 1503:1514 Opuntia ficus-indica anthocyanins 1482:1514 Opuntia ficus-indica anthocyanins 1482:1514 Opuntia ficus-indica anthocyanins can change the microbial diversity and flora composition of the mouse gut and promote the production of short-chain fatty acids. 36290409 0 27 theme Microbiota 52:61 arg1 Composition 63:73 Gut Microbiota Composition 48:73 Gut Microbiota Composition 48:73 Anthocyanins from Opuntia ficus-indica Modulate Gut Microbiota Composition and Improve Short-Chain Fatty Acid Production. 36290409 0 28 from ficus-indica 26:37 arg1 Anthocyanins 0:11 Anthocyanins 0:11 Anthocyanins from Opuntia ficus-indica 0:37 Anthocyanins from Opuntia ficus-indica Modulate Gut Microbiota Composition and Improve Short-Chain Fatty Acid Production. 36290409 7 29 theme propionic 1429:1437 arg1 acid 1439:1442 propionic acid 1429:1442 propionic acid 1429:1442 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 6 30 dep increased 849:857 arg1 < 862:864 p < 0.05 860:870 p < 0.05 860:870 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 7 31 theme acid 1423:1426 arg1 content 1405:1411 the content 1401:1411 the content of acetic acid, propionic acid, and butyric acid 1401:1460 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 6 32 from Bifidobacterium 1029:1043 arg1 tract 1092:1096 the intestinal tract 1077:1096 the intestinal tract of mice 1077:1104 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 8 33 theme gut 1586:1588 arg1 composition 1561:1571 the microbial diversity and flora composition 1527:1571 the microbial diversity and flora composition of the mouse gut 1527:1588 Opuntia ficus-indica anthocyanins can change the microbial diversity and flora composition of the mouse gut and promote the production of short-chain fatty acids. 36290409 4 34 dep In 421:422 arg1 vivo 424:427 vivo 424:427 vivo 424:427 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 6 35 theme Prevotella 1046:1055 arg1 abundances 980:989 the relative abundances 967:989 the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice 967:1104 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 8 36 theme microbial 1531:1539 arg1 composition 1561:1571 the microbial diversity and flora composition 1527:1571 the microbial diversity and flora composition of the mouse gut 1527:1588 Opuntia ficus-indica anthocyanins can change the microbial diversity and flora composition of the mouse gut and promote the production of short-chain fatty acids. 36290409 6 37 dep decreased 942:950 arg1 < 955:957 p < 0.05 953:963 p < 0.05 953:963 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 38 theme Bifidobacterium 1029:1043 arg1 abundances 980:989 the relative abundances 967:989 the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice 967:1104 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 4 39 theme NovaSeq 571:577 arg1 platform 584:591 NovaSeq 6000 platform 571:591 NovaSeq 6000 platform 571:591 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 39 theme NovaSeq 571:577 arg1 sequencing 559:568 rRNA high-throughput sequencing 538:568 rRNA high-throughput sequencing (NovaSeq 6000 platform) 538:592 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 2 40 theme natural 298:304 arg1 plants 306:311 natural plants 298:311 natural plants 298:311 Some studies have shown that anthocyanins extracted from natural plants can regulate intestinal flora. 36290409 7 41 theme fatty 1355:1359 arg1 acids 1361:1365 short-chain fatty acids 1343:1365 short-chain fatty acids 1343:1365 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 6 42 theme pathogenic 1180:1189 arg1 Escherichia-Shigella 1200:1219 Escherichia-Shigella 1200:1219 Escherichia-Shigella 1200:1219 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 42 theme pathogenic 1180:1189 arg1 bacteria 1191:1198 pathogenic bacteria Escherichia-Shigella and Desulfovibrio 1180:1237 pathogenic bacteria Escherichia-Shigella and Desulfovibrio 1180:1237 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 42 theme pathogenic 1180:1189 arg1 Desulfovibrio 1225:1237 Desulfovibrio 1225:1237 Desulfovibrio 1225:1237 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 8 43 theme short-chain 1620:1630 arg1 acids 1638:1642 short-chain fatty acids 1620:1642 short-chain fatty acids 1620:1642 Opuntia ficus-indica anthocyanins can change the microbial diversity and flora composition of the mouse gut and promote the production of short-chain fatty acids. 36290409 1 44 theme substances 174:183 arg1 variety 156:162 a variety 154:162 a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides 154:238 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 44 theme substances 174:183 arg1 substances 174:183 active substances 167:183 active substances 167:183 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 44 theme substances 174:183 arg1 flavonoids 208:217 flavonoids 208:217 flavonoids 208:217 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 44 theme substances 174:183 arg1 polysaccharides 224:238 polysaccharides 224:238 polysaccharides 224:238 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 1 44 theme substances 174:183 arg1 anthocyanins 194:205 anthocyanins 194:205 anthocyanins 194:205 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 7 45 theme mice 1383:1386 arg1 cecum 1374:1378 the cecum 1370:1378 the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most 1370:1479 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 4 46 used used 446:449 arg2 experiments 429:439 In vivo experiments 421:439 In vivo experiments 421:439 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 47 from effect 464:469 arg1 intestine 521:529 the mouse intestine 511:529 the mouse intestine 511:529 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 6 48 theme feeding 758:764 arg1 anthocyanins 766:777 feeding anthocyanins 758:777 feeding anthocyanins 758:777 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 2 49 theme intestinal 326:335 arg1 flora 337:341 intestinal flora 326:341 intestinal flora 326:341 Some studies have shown that anthocyanins extracted from natural plants can regulate intestinal flora. 36290409 8 50 theme acids 1638:1642 arg1 production 1606:1615 the production 1602:1615 the production of short-chain fatty acids 1602:1642 Opuntia ficus-indica anthocyanins can change the microbial diversity and flora composition of the mouse gut and promote the production of short-chain fatty acids. 36290409 6 51 dep decreased 1239:1247 arg1 < 1266:1268 p < 0.05 1264:1274 p < 0.05 1264:1274 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 7 52 theme acids 1361:1365 arg1 content 1332:1338 the content 1328:1338 the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most 1328:1479 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 6 53 from abundances 980:989 arg1 tract 1092:1096 the intestinal tract 1077:1096 the intestinal tract of mice 1077:1104 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 54 theme intestinal 1081:1090 arg1 tract 1092:1096 the intestinal tract 1077:1096 the intestinal tract of mice 1077:1104 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 4 55 theme hydrogen 618:625 arg1 FID 654:656 FID 654:656 FID 654:656 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 55 theme hydrogen 618:625 arg1 detector 644:651 hydrogen flame ionization detector 618:651 hydrogen flame ionization detector (FID) 618:657 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 5 56 theme short-chain 695:705 arg1 SCFAs 720:724 SCFAs 720:724 SCFAs 720:724 Microbiota and effects of short-chain fatty acids (SCFAs). 36290409 5 56 theme short-chain 695:705 arg1 acids 713:717 short-chain fatty acids 695:717 short-chain fatty acids (SCFAs) 695:725 Microbiota and effects of short-chain fatty acids (SCFAs). 36290409 6 57 theme F/B 913:915 arg1 Firmicutes/Bacteroidetes 887:910 Firmicutes/Bacteroidetes 887:910 Firmicutes/Bacteroidetes (F/B value) 887:922 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 57 theme F/B 913:915 arg1 value 917:921 F/B value 913:921 F/B value 913:921 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 58 dep increased 1125:1133 arg1 < 1138:1140 p < 0.05 1136:1146 p < 0.05 1136:1146 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 59 theme p 1264:1264 arg1 < 1266:1268 p < 0.05 1264:1274 p < 0.05 1264:1274 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 8 60 dep Opuntia 1482:1488 arg1 ficus-indica 1490:1501 ficus-indica 1490:1501 ficus-indica 1490:1501 Opuntia ficus-indica anthocyanins can change the microbial diversity and flora composition of the mouse gut and promote the production of short-chain fatty acids. 36290409 6 61 theme Firmicutes/Bacteroidetes 887:910 arg1 ratio 878:882 the ratio 874:882 the ratio of Firmicutes/Bacteroidetes (F/B value) 874:922 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 4 62 theme In 421:422 arg1 experiments 429:439 In vivo experiments 421:439 In vivo experiments 421:439 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 63 dep chromatography 602:615 arg1 FID 654:656 FID 654:656 FID 654:656 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 63 dep chromatography 602:615 arg1 detector 644:651 hydrogen flame ionization detector 618:651 hydrogen flame ionization detector (FID) 618:657 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 64 theme anthocyanins 495:506 arg1 effect 464:469 the effect 460:469 the effect of Opuntia ficus-indica anthocyanins on the mouse intestine 460:529 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 6 65 theme p 1136:1136 arg1 < 1138:1140 p < 0.05 1136:1146 p < 0.05 1136:1146 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 0 66 theme Fatty 99:103 arg1 Acid 105:108 Short-Chain Fatty Acid 87:108 Short-Chain Fatty Acid Production 87:119 Anthocyanins from Opuntia ficus-indica Modulate Gut Microbiota Composition and Improve Short-Chain Fatty Acid Production. 36290409 6 67 theme microorganisms 808:821 arg1 diversity 784:792 the diversity 780:792 the diversity of intestinal microorganisms in mice 780:829 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 5 68 theme acids 713:717 arg1 Microbiota 669:678 Microbiota 669:678 Microbiota 669:678 Microbiota and effects of short-chain fatty acids (SCFAs). 36290409 5 68 theme acids 713:717 arg1 effects 684:690 effects 684:690 effects 684:690 Microbiota and effects of short-chain fatty acids (SCFAs). 36290409 7 69 theme short-chain 1343:1353 arg1 acids 1361:1365 short-chain fatty acids 1343:1365 short-chain fatty acids 1343:1365 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 3 70 theme raw 366:368 arg1 material 370:377 raw material 366:377 raw material 366:377 The fruit was used as raw material, and anthocyanins were extracted from it. 36290409 3 70 theme raw 366:368 arg1 fruit 348:352 The fruit 344:352 The fruit 344:352 The fruit was used as raw material, and anthocyanins were extracted from it. 36290409 4 71 dep sequencing 559:568 arg1 methods 660:666 methods 660:666 methods 660:666 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 3 72 used used 358:361 arg2 material 370:377 raw material 366:377 raw material 366:377 The fruit was used as raw material, and anthocyanins were extracted from it. 36290409 3 72 used used 358:361 arg2 fruit 348:352 The fruit 344:352 The fruit 344:352 The fruit was used as raw material, and anthocyanins were extracted from it. 36290409 1 73 from variety 156:162 arg1 rich 146:149 rich 146:149 rich 146:149 Opuntia ficus-indica is rich in a variety of active substances, such as anthocyanins, flavonoids, and polysaccharides. 36290409 9 74 theme ficus-indica 1709:1720 arg1 anthocyanins 1722:1733 Opuntia ficus-indica anthocyanins 1701:1733 Opuntia ficus-indica anthocyanins 1701:1733 The findings provide a theoretical basis for the use of Opuntia ficus-indica anthocyanins as dietary supplements to regulate human intestinal flora. 36290409 4 75 theme Opuntia 474:480 arg1 anthocyanins 495:506 Opuntia ficus-indica anthocyanins 474:506 Opuntia ficus-indica anthocyanins 474:506 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 76 theme high-throughput 543:557 arg1 platform 584:591 NovaSeq 6000 platform 571:591 NovaSeq 6000 platform 571:591 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 76 theme high-throughput 543:557 arg1 sequencing 559:568 rRNA high-throughput sequencing 538:568 rRNA high-throughput sequencing (NovaSeq 6000 platform) 538:592 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 6 77 theme intestinal 797:806 arg1 microorganisms 808:821 intestinal microorganisms 797:821 intestinal microorganisms 797:821 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 6 78 from tract 1092:1096 arg1 abundances 980:989 the relative abundances 967:989 the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice 967:1104 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 0 79 theme Gut 48:50 arg1 Composition 63:73 Gut Microbiota Composition 48:73 Gut Microbiota Composition 48:73 Anthocyanins from Opuntia ficus-indica Modulate Gut Microbiota Composition and Improve Short-Chain Fatty Acid Production. 36290409 7 80 theme acid 1457:1460 arg1 content 1405:1411 the content 1401:1411 the content of acetic acid, propionic acid, and butyric acid 1401:1460 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 7 81 from content 1332:1338 arg1 cecum 1374:1378 the cecum 1370:1378 the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most 1370:1479 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 6 82 theme relative 971:978 arg1 abundances 980:989 the relative abundances 967:989 the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice 967:1104 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 9 83 theme intestinal 1776:1785 arg1 flora 1787:1791 human intestinal flora 1770:1791 human intestinal flora 1770:1791 The findings provide a theoretical basis for the use of Opuntia ficus-indica anthocyanins as dietary supplements to regulate human intestinal flora. 36290409 8 84 theme mouse 1580:1584 arg1 gut 1586:1588 the mouse gut 1576:1588 the mouse gut 1576:1588 Opuntia ficus-indica anthocyanins can change the microbial diversity and flora composition of the mouse gut and promote the production of short-chain fatty acids. 36290409 7 85 theme acid 1439:1442 arg1 content 1405:1411 the content 1401:1411 the content of acetic acid, propionic acid, and butyric acid 1401:1460 Furthermore, anthocyanins significantly increased the content of short-chain fatty acids in the cecum of mice, among which the content of acetic acid, propionic acid, and butyric acid increased the most. 36290409 6 86 theme Akkermansia 1062:1072 arg1 abundances 980:989 the relative abundances 967:989 the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice 967:1104 The results showed that after feeding anthocyanins, the diversity of intestinal microorganisms in mice was significantly increased (p < 0.05), the ratio of Firmicutes/Bacteroidetes (F/B value) was significantly decreased (p < 0.05), the relative abundances of beneficial bacteria Lactobacillus, Bifidobacterium, Prevotella, and Akkermansia in the intestinal tract of mice were significantly increased (p < 0.05), and the relative abundance of pathogenic bacteria Escherichia-Shigella and Desulfovibrio decreased significantly (p < 0.05). 36290409 4 87 theme gas 598:600 arg1 chromatography 602:615 gas chromatography 598:615 gas chromatography (hydrogen flame ionization detector (FID)) 598:658 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 88 theme mouse 515:519 arg1 intestine 521:529 the mouse intestine 511:529 the mouse intestine 511:529 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 89 theme ionization 633:642 arg1 FID 654:656 FID 654:656 FID 654:656 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 4 89 theme ionization 633:642 arg1 detector 644:651 hydrogen flame ionization detector 618:651 hydrogen flame ionization detector (FID) 618:657 In vivo experiments were used to study the effect of Opuntia ficus-indica anthocyanins on the mouse intestine by 16S rRNA high-throughput sequencing (NovaSeq 6000 platform) and gas chromatography (hydrogen flame ionization detector (FID)) methods. 36290409 8 90 theme diversity 1541:1549 arg1 composition 1561:1571 the microbial diversity and flora composition 1527:1571 the microbial diversity and flora composition of the mouse gut 1527:1588 Opuntia ficus-indica anthocyanins can change the microbial diversity and flora composition of the mouse gut and promote the production of short-chain fatty acids. 35683335 8 0 theme growth 908:913 arg1 conditions 915:924 the growth conditions 904:924 the growth conditions 904:924 Regardless of the growth conditions, in terms of its chemical composition, bark differs significantly from wood, showing twice the contents of soluble substances in NaOH and lignin and half the content of polysaccharides. 35683335 8 1 from contents 1021:1028 arg1 lignin 1064:1069 lignin 1064:1069 lignin 1064:1069 Regardless of the growth conditions, in terms of its chemical composition, bark differs significantly from wood, showing twice the contents of soluble substances in NaOH and lignin and half the content of polysaccharides. 35683335 8 1 from contents 1021:1028 arg1 NaOH 1055:1058 NaOH 1055:1058 NaOH 1055:1058 Regardless of the growth conditions, in terms of its chemical composition, bark differs significantly from wood, showing twice the contents of soluble substances in NaOH and lignin and half the content of polysaccharides. 35683335 5 2 theme study 351:355 arg1 aim 340:342 The aim 336:342 The aim of the study 336:355 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 9 3 theme components 1176:1185 arg1 range 1149:1153 the range 1145:1153 the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin 1145:1252 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 5 4 theme soluble 573:579 arg1 pentosans 548:556 pentosans 548:556 pentosans 548:556 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 5 theme cellulose 514:522 arg1 contents 502:509 percentage contents 491:509 percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH 491:596 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 11 6 theme most 1383:1386 arg1 elements 1397:1404 most chemical elements 1383:1404 most chemical elements 1383:1404 In bark, a relationship was found between the content of most chemical elements and differing environmental growth conditions. 35683335 9 7 from bark 1190:1193 arg1 range 1149:1153 the range 1145:1153 the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin 1145:1252 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 12 8 theme environmental 1471:1483 arg1 stress 1485:1490 environmental stress 1471:1490 environmental stress 1471:1490 It was shown that environmental stress influenced the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components. 35683335 8 9 theme polysaccharides 1095:1109 arg1 content 1084:1090 the content 1080:1090 the content of polysaccharides 1080:1109 Regardless of the growth conditions, in terms of its chemical composition, bark differs significantly from wood, showing twice the contents of soluble substances in NaOH and lignin and half the content of polysaccharides. 35683335 10 10 from elements 1274:1281 arg1 wood 1295:1298 wood 1295:1298 wood 1295:1298 The main inorganic elements in bark and wood are Na, K, Ca, Mg and Zn. 35683335 10 10 from elements 1274:1281 arg1 bark 1286:1289 bark 1286:1289 bark 1286:1289 The main inorganic elements in bark and wood are Na, K, Ca, Mg and Zn. 35683335 2 11 theme Tilia 127:131 arg1 Mill 141:144 Tilia cordata Mill 127:144 Tilia cordata Mill. 127:145 Tilia cordata Mill. 35683335 3 12 theme urban 175:179 arg1 spaces 181:186 urban spaces 175:186 urban spaces 175:186 is a favourite tree used in urban spaces. 35683335 5 13 theme holocellulose 525:537 arg1 contents 502:509 percentage contents 491:509 percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH 491:596 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 14 theme lignin 540:545 arg1 contents 502:509 percentage contents 491:509 percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH 491:596 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 12 15 theme bark 1542:1545 arg1 properties 1519:1528 the hygroscopic properties 1503:1528 the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components 1503:1611 It was shown that environmental stress influenced the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components. 35683335 5 16 dep properties 479:488 arg1 contents 502:509 percentage contents 491:509 percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH 491:596 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 16 dep properties 479:488 arg1 i.e. 464:467 i.e. 464:467 i.e. 464:467 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 7 17 theme severity 866:873 arg1 stress 848:853 environmental stress 834:853 environmental stress of varying severity 834:873 growing in environments exposed to environmental stress of varying severity were examined. 35683335 12 18 theme percentage 1579:1588 arg1 consequence 1560:1570 a consequence 1558:1570 a consequence of the percentage of chemical components 1558:1611 It was shown that environmental stress influenced the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components. 35683335 12 18 theme percentage 1579:1588 arg1 bark 1542:1545 bark 1542:1545 bark 1542:1545 It was shown that environmental stress influenced the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components. 35683335 12 18 theme percentage 1579:1588 arg1 wood 1533:1536 wood 1533:1536 wood 1533:1536 It was shown that environmental stress influenced the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components. 35683335 9 19 from lignin 1247:1252 arg1 soluble 1213:1219 soluble 1213:1219 soluble 1213:1219 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 5 20 theme sorption 749:756 arg1 isotherms 758:766 sorption isotherms 749:766 sorption isotherms 749:766 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 21 theme trees 432:436 arg1 growth 416:421 the growth 412:421 the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms) 412:767 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 12 22 theme chemical 1593:1600 arg1 components 1602:1611 chemical components 1593:1611 chemical components 1593:1611 It was shown that environmental stress influenced the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components. 35683335 8 23 theme composition 952:962 arg1 terms 930:934 terms 930:934 terms of its chemical composition 930:962 Regardless of the growth conditions, in terms of its chemical composition, bark differs significantly from wood, showing twice the contents of soluble substances in NaOH and lignin and half the content of polysaccharides. 35683335 9 24 from soluble 1213:1219 arg1 lignin 1247:1252 lignin 1247:1252 lignin 1247:1252 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 9 24 from soluble 1213:1219 arg1 ethanol 1224:1230 ethanol 1224:1230 ethanol 1224:1230 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 9 24 from soluble 1213:1219 arg1 cellulose 1233:1241 cellulose 1233:1241 cellulose 1233:1241 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 5 25 theme pentosans 548:556 arg1 contents 502:509 percentage contents 491:509 percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH 491:596 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 26 theme percentage 491:500 arg1 contents 502:509 percentage contents 491:509 percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH 491:596 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 10 27 theme inorganic 1264:1272 arg1 Na 1304:1305 Na 1304:1305 Na 1304:1305 The main inorganic elements in bark and wood are Na, K, Ca, Mg and Zn. 35683335 10 27 theme inorganic 1264:1272 arg1 elements 1274:1281 The main inorganic elements 1255:1281 The main inorganic elements in bark and wood 1255:1298 The main inorganic elements in bark and wood are Na, K, Ca, Mg and Zn. 35683335 0 28 theme Chemical 0:7 arg1 Mill 67:70 Tilia cordata Mill. 53:71 Tilia cordata Mill. 53:71 Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) 35683335 0 28 theme Chemical 0:7 arg1 Composition 9:19 Chemical Composition 0:19 Chemical Composition 0:19 Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) 35683335 7 29 theme varying 858:864 arg1 severity 866:873 varying severity 858:873 varying severity 858:873 growing in environments exposed to environmental stress of varying severity were examined. 35683335 5 30 theme selected 701:708 arg1 properties 722:731 selected hygroscopic properties 701:731 selected hygroscopic properties 701:731 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 9 31 theme soluble 1213:1219 arg1 substances 1202:1211 substances 1202:1211 substances soluble in ethanol, cellulose, or lignin 1202:1252 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 0 32 theme Related 25:31 arg1 Properties 33:42 Related Properties 25:42 Related Properties of Lime 25:50 Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) 35683335 7 33 theme environmental 834:846 arg1 stress 848:853 environmental stress 834:853 environmental stress of varying severity 834:873 growing in environments exposed to environmental stress of varying severity were examined. 35683335 3 34 theme favourite 152:160 arg1 tree 162:165 a favourite tree 150:165 a favourite tree used in urban spaces 150:186 is a favourite tree used in urban spaces. 35683335 5 35 theme hygroscopic 710:720 arg1 properties 722:731 selected hygroscopic properties 701:731 selected hygroscopic properties 701:731 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 36 theme subsequent 448:457 arg1 use 459:461 their subsequent use 442:461 their subsequent use 442:461 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 9 37 from cellulose 1233:1241 arg1 soluble 1213:1219 soluble 1213:1219 soluble 1213:1219 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 4 38 from vegetation 308:317 arg1 spaces 328:333 urban spaces 322:333 urban spaces 322:333 For this reason, it is important to know its sensitivity to environmental stress, which is particularly burdensome for vegetation in urban spaces. 35683335 12 39 theme components 1602:1611 arg1 percentage 1579:1588 the percentage 1575:1588 the percentage of chemical components 1575:1611 It was shown that environmental stress influenced the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components. 35683335 9 40 theme Growth 1112:1117 arg1 conditions 1119:1128 Growth conditions 1112:1128 Growth conditions 1112:1128 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 9 41 from components 1176:1185 arg1 bark 1190:1193 bark 1190:1193 bark 1190:1193 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 11 42 theme chemical 1388:1395 arg1 elements 1397:1404 most chemical elements 1383:1404 most chemical elements 1383:1404 In bark, a relationship was found between the content of most chemical elements and differing environmental growth conditions. 35683335 9 43 dep substances 1202:1211 arg1 e.g. 1196:1199 e.g. 1196:1199 e.g. 1196:1199 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 8 44 theme substances 1041:1050 arg1 contents 1021:1028 the contents 1017:1028 the contents of soluble substances in NaOH and lignin 1017:1069 Regardless of the growth conditions, in terms of its chemical composition, bark differs significantly from wood, showing twice the contents of soluble substances in NaOH and lignin and half the content of polysaccharides. 35683335 5 45 theme chemical 614:621 arg1 elements 623:630 the chemical elements 610:630 the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) 610:695 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 9 46 theme selected 1158:1165 arg1 components 1176:1185 selected chemical components 1158:1185 selected chemical components 1158:1185 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 5 47 from soluble 573:579 arg1 NaOH 584:587 NaOH 584:587 NaOH 584:587 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 10 48 theme main 1259:1262 arg1 Na 1304:1305 Na 1304:1305 Na 1304:1305 The main inorganic elements in bark and wood are Na, K, Ca, Mg and Zn. 35683335 10 48 theme main 1259:1262 arg1 elements 1274:1281 The main inorganic elements 1255:1281 The main inorganic elements in bark and wood 1255:1298 The main inorganic elements in bark and wood are Na, K, Ca, Mg and Zn. 35683335 5 49 from NaOH 584:587 arg1 soluble 573:579 soluble 573:579 soluble 573:579 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 50 dep K 633:633 arg1 Fe 651:652 Fe 651:652 Fe 651:652 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 50 dep K 633:633 arg1 Hg 693:694 Hg 693:694 Hg 693:694 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 50 dep K 633:633 arg1 Na 636:637 Na 636:637 Na 636:637 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 50 dep K 633:633 arg1 Cr 678:679 Cr 678:679 Cr 678:679 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 50 dep K 633:633 arg1 Mg 640:641 Mg 640:641 Mg 640:641 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 50 dep K 633:633 arg1 Zn 655:656 Zn 655:656 Zn 655:656 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 50 dep K 633:633 arg1 Al 682:683 Al 682:683 Al 682:683 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 50 dep K 633:633 arg1 Ca 644:645 Ca 644:645 Ca 644:645 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 2 51 theme cordata 133:139 arg1 Mill 141:144 Tilia cordata Mill 127:144 Tilia cordata Mill. 127:145 Tilia cordata Mill. 35683335 9 52 from range 1149:1153 arg1 bark 1190:1193 bark 1190:1193 bark 1190:1193 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 0 53 theme Lime 47:50 arg1 Mill 67:70 Tilia cordata Mill. 53:71 Tilia cordata Mill. 53:71 Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) 35683335 0 53 theme Lime 47:50 arg1 Composition 9:19 Chemical Composition 0:19 Chemical Composition 0:19 Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) 35683335 0 53 theme Lime 47:50 arg1 Properties 33:42 Related Properties 25:42 Related Properties of Lime 25:50 Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) 35683335 5 54 theme EtOH 593:596 arg1 contents 502:509 percentage contents 491:509 percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH 491:596 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 11 55 theme differing 1410:1418 arg1 conditions 1441:1450 differing environmental growth conditions 1410:1450 differing environmental growth conditions 1410:1450 In bark, a relationship was found between the content of most chemical elements and differing environmental growth conditions. 35683335 5 56 theme chemical 470:477 arg1 properties 479:488 chemical properties 470:488 chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms) 470:767 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 4 57 theme urban 322:326 arg1 spaces 328:333 urban spaces 322:333 urban spaces 322:333 For this reason, it is important to know its sensitivity to environmental stress, which is particularly burdensome for vegetation in urban spaces. 35683335 5 58 dep elements 623:630 arg1 K 633:633 K 633:633 K 633:633 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 58 dep elements 623:630 arg1 hysteresis 734:743 hysteresis 734:743 hysteresis 734:743 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 5 58 dep elements 623:630 arg1 isotherms 758:766 sorption isotherms 749:766 sorption isotherms 749:766 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 11 59 theme environmental 1420:1432 arg1 conditions 1441:1450 differing environmental growth conditions 1410:1450 differing environmental growth conditions 1410:1450 In bark, a relationship was found between the content of most chemical elements and differing environmental growth conditions. 35683335 9 60 from ethanol 1224:1230 arg1 soluble 1213:1219 soluble 1213:1219 soluble 1213:1219 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35683335 12 61 theme hygroscopic 1507:1517 arg1 properties 1519:1528 the hygroscopic properties 1503:1528 the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components 1503:1611 It was shown that environmental stress influenced the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components. 35683335 6 62 theme Mill 793:796 arg1 Trees 770:774 Trees 770:774 Trees of Tilia cordata Mill 770:796 Trees of Tilia cordata Mill. 35683335 12 63 theme wood 1533:1536 arg1 properties 1519:1528 the hygroscopic properties 1503:1528 the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components 1503:1611 It was shown that environmental stress influenced the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components. 35683335 11 64 theme elements 1397:1404 arg1 content 1372:1378 the content 1368:1378 the content of most chemical elements and differing environmental growth conditions 1368:1450 In bark, a relationship was found between the content of most chemical elements and differing environmental growth conditions. 35683335 8 65 theme chemical 943:950 arg1 composition 952:962 its chemical composition 939:962 its chemical composition 939:962 Regardless of the growth conditions, in terms of its chemical composition, bark differs significantly from wood, showing twice the contents of soluble substances in NaOH and lignin and half the content of polysaccharides. 35683335 1 66 theme Tree 103:106 arg1 Conditions 115:124 Tree Growth Conditions 103:124 Tree Growth Conditions 103:124 Bark and Wood as Affected by Tree Growth Conditions. 35683335 11 67 located found 1354:1358 arg1 bark 1329:1332 bark 1329:1332 bark 1329:1332 In bark, a relationship was found between the content of most chemical elements and differing environmental growth conditions. 35683335 11 67 located found 1354:1358 arg2 relationship 1337:1348 a relationship 1335:1348 a relationship 1335:1348 In bark, a relationship was found between the content of most chemical elements and differing environmental growth conditions. 35683335 6 68 theme cordata 785:791 arg1 Mill 793:796 Tilia cordata Mill 779:796 Tilia cordata Mill 779:796 Trees of Tilia cordata Mill. 35683335 0 69 theme cordata 59:65 arg1 Mill 67:70 Tilia cordata Mill. 53:71 Tilia cordata Mill. 53:71 Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) 35683335 0 69 theme cordata 59:65 arg1 Composition 9:19 Chemical Composition 0:19 Chemical Composition 0:19 Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) 35683335 8 70 theme soluble 1033:1039 arg1 substances 1041:1050 soluble substances 1033:1050 soluble substances 1033:1050 Regardless of the growth conditions, in terms of its chemical composition, bark differs significantly from wood, showing twice the contents of soluble substances in NaOH and lignin and half the content of polysaccharides. 35683335 11 71 theme growth 1434:1439 arg1 conditions 1441:1450 differing environmental growth conditions 1410:1450 differing environmental growth conditions 1410:1450 In bark, a relationship was found between the content of most chemical elements and differing environmental growth conditions. 35683335 4 72 theme environmental 249:261 arg1 stress 263:268 environmental stress 249:268 environmental stress 249:268 For this reason, it is important to know its sensitivity to environmental stress, which is particularly burdensome for vegetation in urban spaces. 35683335 1 73 theme Growth 108:113 arg1 Conditions 115:124 Tree Growth Conditions 103:124 Tree Growth Conditions 103:124 Bark and Wood as Affected by Tree Growth Conditions. 35683335 5 74 theme necessary 391:399 arg1 properties 380:389 the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms) 376:767 the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms) 376:767 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 6 75 theme Tilia 779:783 arg1 Mill 793:796 Tilia cordata Mill 779:796 Tilia cordata Mill 779:796 Trees of Tilia cordata Mill. 35683335 0 76 theme Tilia 53:57 arg1 Mill 67:70 Tilia cordata Mill. 53:71 Tilia cordata Mill. 53:71 Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) 35683335 0 76 theme Tilia 53:57 arg1 Composition 9:19 Chemical Composition 0:19 Chemical Composition 0:19 Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) 35683335 11 77 theme conditions 1441:1450 arg1 content 1372:1378 the content 1368:1378 the content of most chemical elements and differing environmental growth conditions 1368:1450 In bark, a relationship was found between the content of most chemical elements and differing environmental growth conditions. 35683335 5 78 theme use 459:461 arg1 growth 416:421 the growth 412:421 the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms) 412:767 The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). 35683335 9 79 theme chemical 1167:1174 arg1 components 1176:1185 selected chemical components 1158:1185 selected chemical components 1158:1185 Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. 35458538 2 0 theme Vpu 281:283 arg1 end 274:276 3' end 271:276 3' end of Vpu 271:283 Env is generated from Vpu/Env encoded bicistronic mRNA such that the 5' end of Env-N-terminus, that encodes for Env-SP overlaps with 3' end of Vpu. 35458538 5 1 theme other 642:646 arg1 isolates 654:661 other HIV-1 isolates 642:661 other HIV-1 isolates 642:661 We used infectious molecular clone pNL4.3-CMU06 and swapped its SP (or VEOR) with that from other HIV-1 isolates. 35458538 0 2 from Role 5:8 arg1 Evasion 53:59 Immune Evasion 46:59 Immune Evasion 46:59 Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion. 35458538 11 3 from diversity 1239:1247 arg1 VEOR 1252:1255 VEOR 1252:1255 VEOR 1252:1255 Our study suggests that genetic diversity in VEOR plays an important role in the differential pathogenesis and also assist in immune evasion by altering Env epitope exposure. 35458538 1 4 theme Env 123:125 arg1 functions 127:135 Env functions 123:135 Env functions 123:135 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 5 5 used used 553:556 arg2 We 550:551 We 550:551 We 550:551 We used infectious molecular clone pNL4.3-CMU06 and swapped its SP (or VEOR) with that from other HIV-1 isolates. 35458538 4 6 from effect 418:423 arg1 region 477:482 the Vpu-Env overlapping region 453:482 the Vpu-Env overlapping region (VEOR) 453:489 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 6 from effect 418:423 arg1 functions 498:506 the functions 494:506 the functions of two vital viral proteins: Vpu and Env 494:547 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 6 from effect 418:423 arg1 VEOR 485:488 VEOR 485:488 VEOR 485:488 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 10 7 theme oligosaccharide 1102:1116 arg1 composition 1118:1128 the oligosaccharide composition 1098:1128 the oligosaccharide composition of Env-N-glycans 1098:1145 These swaps affected the oligosaccharide composition of Env-N-glycans as shown by changes in DC-SIGN-mediated virus transmission. 35458538 3 8 theme Env 286:288 arg1 SP 290:291 Env SP 286:291 Env SP 286:291 Env SP displays high sequence diversity, which translates into high variability in Vpu sequence. 35458538 6 9 theme tetherin 758:765 arg1 presence 746:753 presence 746:753 presence of tetherin 746:765 Swapping VEOR did not affect virus production in the absence of tetherin however, presence of tetherin significantly altered the release of virus progeny. 35458538 9 10 theme antigenic 1040:1048 arg1 landscape 1050:1058 the antigenic landscape 1036:1058 the antigenic landscape of swapped Envs 1036:1074 Analyzing the binding of monoclonal antibodies to membrane embedded Env revealed changes in the antigenic landscape of swapped Envs. 35458538 0 11 theme Dual 0:3 arg1 Role 5:8 Dual Role 0:8 Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion. 0:60 Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion. 35458538 11 12 theme differential 1288:1299 arg1 pathogenesis 1301:1312 the differential pathogenesis 1284:1312 the differential pathogenesis 1284:1312 Our study suggests that genetic diversity in VEOR plays an important role in the differential pathogenesis and also assist in immune evasion by altering Env epitope exposure. 35458538 2 13 theme Env-N-terminus 217:230 arg1 end 210:212 the 5' end 203:212 the 5' end of Env-N-terminus, that encodes for Env-SP 203:255 Env is generated from Vpu/Env encoded bicistronic mRNA such that the 5' end of Env-N-terminus, that encodes for Env-SP overlaps with 3' end of Vpu. 35458538 11 14 theme genetic 1231:1237 arg1 diversity 1239:1247 genetic diversity 1231:1247 genetic diversity in VEOR 1231:1255 Our study suggests that genetic diversity in VEOR plays an important role in the differential pathogenesis and also assist in immune evasion by altering Env epitope exposure. 35458538 4 15 from polymorphism 437:448 arg1 region 477:482 the Vpu-Env overlapping region 453:482 the Vpu-Env overlapping region (VEOR) 453:489 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 15 from polymorphism 437:448 arg1 VEOR 485:488 VEOR 485:488 VEOR 485:488 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 5 16 theme HIV-1 648:652 arg1 isolates 654:661 other HIV-1 isolates 642:661 other HIV-1 isolates 642:661 We used infectious molecular clone pNL4.3-CMU06 and swapped its SP (or VEOR) with that from other HIV-1 isolates. 35458538 6 17 theme Swapping 664:671 arg1 VEOR 673:676 Swapping VEOR 664:676 Swapping VEOR 664:676 Swapping VEOR did not affect virus production in the absence of tetherin however, presence of tetherin significantly altered the release of virus progeny. 35458538 1 18 theme HIV-1 62:66 arg1 contributor 108:118 an important contributor 95:118 an important contributor to Env functions 95:135 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 1 18 theme HIV-1 62:66 arg1 SP 88:89 SP 88:89 SP 88:89 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 1 18 theme HIV-1 62:66 arg1 peptide 79:85 HIV-1 Env signal peptide 62:85 HIV-1 Env signal peptide (SP) 62:90 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 6 19 theme virus 804:808 arg1 progeny 810:816 virus progeny 804:816 virus progeny 804:816 Swapping VEOR did not affect virus production in the absence of tetherin however, presence of tetherin significantly altered the release of virus progeny. 35458538 3 20 theme high 302:305 arg1 diversity 316:324 high sequence diversity 302:324 high sequence diversity 302:324 Env SP displays high sequence diversity, which translates into high variability in Vpu sequence. 35458538 8 21 theme swaps 920:924 arg1 effect 904:909 the effect 900:909 the effect of these swaps on Env functions 900:941 We next tested the effect of these swaps on Env functions. 35458538 9 22 theme swapped 1063:1069 arg1 Envs 1071:1074 swapped Envs 1063:1074 swapped Envs 1063:1074 Analyzing the binding of monoclonal antibodies to membrane embedded Env revealed changes in the antigenic landscape of swapped Envs. 35458538 1 23 theme Env 68:70 arg1 contributor 108:118 an important contributor 95:118 an important contributor to Env functions 95:135 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 1 23 theme Env 68:70 arg1 SP 88:89 SP 88:89 SP 88:89 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 1 23 theme Env 68:70 arg1 peptide 79:85 HIV-1 Env signal peptide 62:85 HIV-1 Env signal peptide (SP) 62:90 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 3 24 theme sequence 307:314 arg1 diversity 316:324 high sequence diversity 302:324 high sequence diversity 302:324 Env SP displays high sequence diversity, which translates into high variability in Vpu sequence. 35458538 9 25 theme Envs 1071:1074 arg1 landscape 1050:1058 the antigenic landscape 1036:1058 the antigenic landscape of swapped Envs 1036:1074 Analyzing the binding of monoclonal antibodies to membrane embedded Env revealed changes in the antigenic landscape of swapped Envs. 35458538 1 26 theme signal 72:77 arg1 contributor 108:118 an important contributor 95:118 an important contributor to Env functions 95:135 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 1 26 theme signal 72:77 arg1 SP 88:89 SP 88:89 SP 88:89 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 1 26 theme signal 72:77 arg1 peptide 79:85 HIV-1 Env signal peptide 62:85 HIV-1 Env signal peptide (SP) 62:90 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 3 27 theme high 349:352 arg1 variability 354:364 high variability 349:364 high variability in Vpu sequence 349:380 Env SP displays high sequence diversity, which translates into high variability in Vpu sequence. 35458538 0 28 theme HIV-1 13:17 arg1 Peptide 35:41 HIV-1 Envelope Signal Peptide 13:41 HIV-1 Envelope Signal Peptide 13:41 Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion. 35458538 4 29 theme overlapping 465:475 arg1 region 477:482 the Vpu-Env overlapping region 453:482 the Vpu-Env overlapping region (VEOR) 453:489 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 29 theme overlapping 465:475 arg1 VEOR 485:488 VEOR 485:488 VEOR 485:488 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 8 30 theme Env 929:931 arg1 functions 933:941 Env functions 929:941 Env functions 929:941 We next tested the effect of these swaps on Env functions. 35458538 4 31 dep proteins 527:534 arg1 Vpu 537:539 Vpu 537:539 Vpu 537:539 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 31 dep proteins 527:534 arg1 proteins 527:534 two vital viral proteins 511:534 two vital viral proteins: Vpu and Env 511:547 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 31 dep proteins 527:534 arg1 Env 545:547 Env 545:547 Env 545:547 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 10 32 theme virus 1187:1191 arg1 transmission 1193:1204 DC-SIGN-mediated virus transmission 1170:1204 DC-SIGN-mediated virus transmission 1170:1204 These swaps affected the oligosaccharide composition of Env-N-glycans as shown by changes in DC-SIGN-mediated virus transmission. 35458538 5 33 theme swapped 602:608 arg1 VEOR 621:624 VEOR 621:624 VEOR 621:624 We used infectious molecular clone pNL4.3-CMU06 and swapped its SP (or VEOR) with that from other HIV-1 isolates. 35458538 5 33 theme swapped 602:608 arg1 SP 614:615 swapped its SP 602:615 swapped its SP (or VEOR) 602:625 We used infectious molecular clone pNL4.3-CMU06 and swapped its SP (or VEOR) with that from other HIV-1 isolates. 35458538 11 34 theme immune 1333:1338 arg1 evasion 1340:1346 immune evasion 1333:1346 immune evasion 1333:1346 Our study suggests that genetic diversity in VEOR plays an important role in the differential pathogenesis and also assist in immune evasion by altering Env epitope exposure. 35458538 10 35 theme DC-SIGN-mediated 1170:1185 arg1 transmission 1193:1204 DC-SIGN-mediated virus transmission 1170:1204 DC-SIGN-mediated virus transmission 1170:1204 These swaps affected the oligosaccharide composition of Env-N-glycans as shown by changes in DC-SIGN-mediated virus transmission. 35458538 4 36 theme proteins 527:534 arg1 functions 498:506 the functions 494:506 the functions of two vital viral proteins: Vpu and Env 494:547 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 0 37 theme Signal 28:33 arg1 Peptide 35:41 HIV-1 Envelope Signal Peptide 13:41 HIV-1 Envelope Signal Peptide 13:41 Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion. 35458538 6 38 theme tetherin 728:735 arg1 absence 717:723 the absence 713:723 the absence of tetherin 713:735 Swapping VEOR did not affect virus production in the absence of tetherin however, presence of tetherin significantly altered the release of virus progeny. 35458538 11 39 theme Env 1360:1362 arg1 exposure 1372:1379 Env epitope exposure 1360:1379 Env epitope exposure 1360:1379 Our study suggests that genetic diversity in VEOR plays an important role in the differential pathogenesis and also assist in immune evasion by altering Env epitope exposure. 35458538 3 40 theme Vpu 369:371 arg1 sequence 373:380 Vpu sequence 369:380 Vpu sequence 369:380 Env SP displays high sequence diversity, which translates into high variability in Vpu sequence. 35458538 0 41 theme Envelope 19:26 arg1 Peptide 35:41 HIV-1 Envelope Signal Peptide 13:41 HIV-1 Envelope Signal Peptide 13:41 Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion. 35458538 4 42 from region 477:482 arg1 effect 418:423 the effect 414:423 the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env 414:547 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 43 theme sequence 428:435 arg1 polymorphism 437:448 sequence polymorphism 428:448 sequence polymorphism in the Vpu-Env overlapping region (VEOR) 428:489 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 44 theme polymorphism 437:448 arg1 effect 418:423 the effect 414:423 the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env 414:547 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 5 45 theme infectious 558:567 arg1 clone 579:583 infectious molecular clone pNL4.3-CMU06 558:596 infectious molecular clone pNL4.3-CMU06 558:596 We used infectious molecular clone pNL4.3-CMU06 and swapped its SP (or VEOR) with that from other HIV-1 isolates. 35458538 11 46 theme important 1266:1274 arg1 role 1276:1279 an important role 1263:1279 an important role 1263:1279 Our study suggests that genetic diversity in VEOR plays an important role in the differential pathogenesis and also assist in immune evasion by altering Env epitope exposure. 35458538 10 47 from changes 1159:1165 arg1 transmission 1193:1204 DC-SIGN-mediated virus transmission 1170:1204 DC-SIGN-mediated virus transmission 1170:1204 These swaps affected the oligosaccharide composition of Env-N-glycans as shown by changes in DC-SIGN-mediated virus transmission. 35458538 9 48 theme antibodies 980:989 arg1 binding 958:964 the binding 954:964 the binding of monoclonal antibodies to membrane embedded Env 954:1014 Analyzing the binding of monoclonal antibodies to membrane embedded Env revealed changes in the antigenic landscape of swapped Envs. 35458538 0 49 theme Peptide 35:41 arg1 Role 5:8 Dual Role 0:8 Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion. 0:60 Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion. 35458538 4 50 theme Vpu-Env 457:463 arg1 region 477:482 the Vpu-Env overlapping region 453:482 the Vpu-Env overlapping region (VEOR) 453:489 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 50 theme Vpu-Env 457:463 arg1 VEOR 485:488 VEOR 485:488 VEOR 485:488 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 5 51 theme molecular 569:577 arg1 clone 579:583 infectious molecular clone pNL4.3-CMU06 558:596 infectious molecular clone pNL4.3-CMU06 558:596 We used infectious molecular clone pNL4.3-CMU06 and swapped its SP (or VEOR) with that from other HIV-1 isolates. 35458538 2 52 theme bicistronic 176:186 arg1 mRNA 188:191 bicistronic mRNA such that the 5' end of Env-N-terminus, that encodes for Env-SP overlaps with 3' end of Vpu 176:283 bicistronic mRNA such that the 5' end of Env-N-terminus, that encodes for Env-SP overlaps with 3' end of Vpu 176:283 Env is generated from Vpu/Env encoded bicistronic mRNA such that the 5' end of Env-N-terminus, that encodes for Env-SP overlaps with 3' end of Vpu. 35458538 11 53 theme epitope 1364:1370 arg1 exposure 1372:1379 Env epitope exposure 1360:1379 Env epitope exposure 1360:1379 Our study suggests that genetic diversity in VEOR plays an important role in the differential pathogenesis and also assist in immune evasion by altering Env epitope exposure. 35458538 8 54 from effect 904:909 arg1 functions 933:941 Env functions 929:941 Env functions 929:941 We next tested the effect of these swaps on Env functions. 35458538 2 55 dep overlaps 257:264 arg1 such 193:196 such 193:196 such 193:196 Env is generated from Vpu/Env encoded bicistronic mRNA such that the 5' end of Env-N-terminus, that encodes for Env-SP overlaps with 3' end of Vpu. 35458538 9 56 theme monoclonal 969:978 arg1 antibodies 980:989 monoclonal antibodies 969:989 monoclonal antibodies 969:989 Analyzing the binding of monoclonal antibodies to membrane embedded Env revealed changes in the antigenic landscape of swapped Envs. 35458538 9 57 theme embedded 1003:1010 arg1 Env 1012:1014 membrane embedded Env 994:1014 membrane embedded Env 994:1014 Analyzing the binding of monoclonal antibodies to membrane embedded Env revealed changes in the antigenic landscape of swapped Envs. 35458538 6 58 theme virus 693:697 arg1 production 699:708 virus production 693:708 virus production in the absence of tetherin 693:735 Swapping VEOR did not affect virus production in the absence of tetherin however, presence of tetherin significantly altered the release of virus progeny. 35458538 10 59 theme Env-N-glycans 1133:1145 arg1 composition 1118:1128 the oligosaccharide composition 1098:1128 the oligosaccharide composition of Env-N-glycans 1098:1145 These swaps affected the oligosaccharide composition of Env-N-glycans as shown by changes in DC-SIGN-mediated virus transmission. 35458538 1 60 theme important 98:106 arg1 contributor 108:118 an important contributor 95:118 an important contributor to Env functions 95:135 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 1 60 theme important 98:106 arg1 peptide 79:85 HIV-1 Env signal peptide 62:85 HIV-1 Env signal peptide (SP) 62:90 HIV-1 Env signal peptide (SP) is an important contributor to Env functions. 35458538 9 61 from changes 1025:1031 arg1 landscape 1050:1058 the antigenic landscape 1036:1058 the antigenic landscape of swapped Envs 1036:1074 Analyzing the binding of monoclonal antibodies to membrane embedded Env revealed changes in the antigenic landscape of swapped Envs. 35458538 4 62 theme viral 521:525 arg1 Vpu 537:539 Vpu 537:539 Vpu 537:539 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 62 theme viral 521:525 arg1 proteins 527:534 two vital viral proteins 511:534 two vital viral proteins: Vpu and Env 511:547 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 62 theme viral 521:525 arg1 Env 545:547 Env 545:547 Env 545:547 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 0 63 theme Immune 46:51 arg1 Evasion 53:59 Immune Evasion 46:59 Immune Evasion 46:59 Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion. 35458538 6 64 from production 699:708 arg1 absence 717:723 the absence 713:723 the absence of tetherin 713:735 Swapping VEOR did not affect virus production in the absence of tetherin however, presence of tetherin significantly altered the release of virus progeny. 35458538 3 65 from variability 354:364 arg1 sequence 373:380 Vpu sequence 369:380 Vpu sequence 369:380 Env SP displays high sequence diversity, which translates into high variability in Vpu sequence. 35458538 6 66 theme progeny 810:816 arg1 release 793:799 the release 789:799 the release of virus progeny 789:816 Swapping VEOR did not affect virus production in the absence of tetherin however, presence of tetherin significantly altered the release of virus progeny. 35458538 4 67 theme vital 515:519 arg1 Vpu 537:539 Vpu 537:539 Vpu 537:539 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 67 theme vital 515:519 arg1 proteins 527:534 two vital viral proteins 511:534 two vital viral proteins: Vpu and Env 511:547 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35458538 4 67 theme vital 515:519 arg1 Env 545:547 Env 545:547 Env 545:547 This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. 35997275 0 0 theme Chromatography 63:76 arg1 Times 88:92 Liquid Chromatography Retention Times 56:92 Liquid Chromatography Retention Times 56:92 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 0 1 from Set 7:9 arg1 Oligosaccharides 127:142 71 Pyridylaminated N-Linked Oligosaccharides 99:142 71 Pyridylaminated N-Linked Oligosaccharides 99:142 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 5 2 from set 764:766 arg1 times 804:808 retention times 794:808 retention times 794:808 A data set on collision drift times, retention times, and molecular mass was collected for these PA-oligosaccharides. 35997275 5 2 from set 764:766 arg1 mass 825:828 molecular mass 815:828 molecular mass 815:828 A data set on collision drift times, retention times, and molecular mass was collected for these PA-oligosaccharides. 35997275 5 2 from set 764:766 arg1 times 787:791 collision drift times 771:791 collision drift times 771:791 A data set on collision drift times, retention times, and molecular mass was collected for these PA-oligosaccharides. 35997275 3 3 theme liquid 553:558 arg1 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 3 3 theme liquid 553:558 arg1 spectrometry 603:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry 536:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS) 536:627 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 1 4 theme glycoconjugates 269:283 arg1 relationships 240:252 structure-function relationships 221:252 structure-function relationships of glycans and glycoconjugates including biopharmaceuticals 221:312 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 1 4 theme glycoconjugates 269:283 arg1 biopharmaceuticals 295:312 biopharmaceuticals 295:312 biopharmaceuticals 295:312 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 0 5 theme Liquid 56:61 arg1 Times 88:92 Liquid Chromatography Retention Times 56:92 Liquid Chromatography Retention Times 56:92 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 1 6 theme glycan 166:171 arg1 structure 173:181 the glycan structure 162:181 the glycan structure 162:181 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 0 7 theme Times 88:92 arg1 Set 7:9 A Data Set 0:9 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 0:143 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 0 7 theme Times 88:92 arg1 Times 88:92 Liquid Chromatography Retention Times 56:92 Liquid Chromatography Retention Times 56:92 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 0 7 theme Times 88:92 arg1 Sections 43:50 Ion Mobility Collision Cross Sections 14:50 Ion Mobility Collision Cross Sections 14:50 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 8 8 theme index 1424:1428 arg1 database 1403:1410 the database 1399:1410 the database of m/z, CCS index, and normalized retention time (GU) 1399:1464 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 7 9 theme PA-oligosaccharide 1152:1169 arg1 value 1138:1142 the CCS value 1130:1142 the CCS value of each PA-oligosaccharide 1130:1169 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 7 10 theme target 1235:1240 arg1 PA-glycan 1242:1250 a target PA-glycan 1233:1250 a target PA-glycan 1233:1250 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 0 11 theme Retention 78:86 arg1 Times 88:92 Liquid Chromatography Retention Times 56:92 Liquid Chromatography Retention Times 56:92 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 5 12 theme collision 771:779 arg1 times 787:791 collision drift times 771:791 collision drift times 771:791 A data set on collision drift times, retention times, and molecular mass was collected for these PA-oligosaccharides. 35997275 7 13 theme standard 1268:1275 arg1 oligomer 1288:1295 the putative standard PA-glucose oligomer 1255:1295 the putative standard PA-glucose oligomer of the same m/z 1255:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 7 14 theme putative 1259:1266 arg1 oligomer 1288:1295 the putative standard PA-glucose oligomer 1255:1295 the putative standard PA-glucose oligomer of the same m/z 1255:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 3 15 theme structures 522:531 arg1 identification 495:508 rapid and precise identification 477:508 rapid and precise identification of N-glycan structures 477:531 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 7 16 theme CCS 1220:1222 arg1 index 1192:1196 a CCS index 1186:1196 a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z 1186:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 7 16 theme CCS 1220:1222 arg1 ratio 1224:1228 a CCS ratio 1218:1228 a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z 1218:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 3 17 theme mass 598:601 arg1 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 3 17 theme mass 598:601 arg1 spectrometry 603:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry 536:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS) 536:627 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 1 18 theme structure 173:181 arg1 step 199:202 an essential step 186:202 an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals 186:312 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 1 18 theme structure 173:181 arg1 Determination 145:157 Determination 145:157 Determination of the glycan structure 145:181 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 7 19 theme CCS 1188:1190 arg1 index 1192:1196 a CCS index 1186:1196 a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z 1186:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 7 19 theme CCS 1188:1190 arg1 ratio 1224:1228 a CCS ratio 1218:1228 a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z 1218:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 6 20 theme glucose 955:961 arg1 units 963:967 glucose units 955:967 glucose units (GU) 955:972 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 6 20 theme glucose 955:961 arg1 GU 970:971 GU 970:971 GU 970:971 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 6 21 from times 1051:1055 arg1 IM-MS 1060:1064 IM-MS 1060:1064 IM-MS 1060:1064 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 6 22 theme retention 918:926 arg1 times 928:932 LC retention times 915:932 LC retention times 915:932 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 2 23 theme Mass 315:318 arg1 spectrometry 320:331 Mass spectrometry 315:331 Mass spectrometry 315:331 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 2 23 theme Mass 315:318 arg1 means 403:407 an excellent means 390:407 an excellent means of analyzing glycan structures 390:438 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 2 24 theme glycan 422:427 arg1 structures 429:438 glycan structures 422:438 glycan structures 422:438 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 0 25 theme Data 2:5 arg1 Set 7:9 A Data Set 0:9 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 0:143 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 0 25 theme Data 2:5 arg1 Times 88:92 Liquid Chromatography Retention Times 56:92 Liquid Chromatography Retention Times 56:92 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 0 25 theme Data 2:5 arg1 Sections 43:50 Ion Mobility Collision Cross Sections 14:50 Ion Mobility Collision Cross Sections 14:50 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 7 26 theme PA-glycan 1242:1250 arg1 index 1192:1196 a CCS index 1186:1196 a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z 1186:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 7 26 theme PA-glycan 1242:1250 arg1 ratio 1224:1228 a CCS ratio 1218:1228 a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z 1218:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 7 27 theme CCS 1134:1136 arg1 value 1138:1142 the CCS value 1130:1142 the CCS value of each PA-oligosaccharide 1130:1169 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 2 28 theme sensitivity 354:364 arg1 spectrometry 320:331 Mass spectrometry 315:331 Mass spectrometry 315:331 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 2 28 theme sensitivity 354:364 arg1 means 403:407 an excellent means 390:407 an excellent means of analyzing glycan structures 390:438 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 6 29 theme drift 1045:1049 arg1 times 1051:1055 drift times 1045:1055 drift times in IM-MS 1045:1064 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 2 30 theme high 349:352 arg1 sensitivity 354:364 its high sensitivity 345:364 its high sensitivity 345:364 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 8 31 theme glycans 1382:1388 arg1 analysis 1361:1368 practical structural analysis 1340:1368 practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU) 1340:1464 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 1 32 theme essential 189:197 arg1 Determination 145:157 Determination 145:157 Determination of the glycan structure 145:181 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 1 32 theme essential 189:197 arg1 step 199:202 an essential step 186:202 an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals 186:312 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 8 33 link N-linked 1373:1380 arg1 glycans 1382:1388 N-linked glycans 1373:1388 N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU) 1373:1464 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 0 34 theme N-Linked 118:125 arg1 Oligosaccharides 127:142 71 Pyridylaminated N-Linked Oligosaccharides 99:142 71 Pyridylaminated N-Linked Oligosaccharides 99:142 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 8 35 theme practical 1340:1348 arg1 analysis 1361:1368 practical structural analysis 1340:1368 practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU) 1340:1464 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 6 36 theme LC 915:916 arg1 times 928:932 LC retention times 915:932 LC retention times 915:932 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 0 37 theme Pyridylaminated 102:116 arg1 Oligosaccharides 127:142 71 Pyridylaminated N-Linked Oligosaccharides 99:142 71 Pyridylaminated N-Linked Oligosaccharides 99:142 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 8 38 theme time 1456:1459 arg1 database 1403:1410 the database 1399:1410 the database of m/z, CCS index, and normalized retention time (GU) 1399:1464 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 3 39 theme chromatography-connected 560:583 arg1 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 3 39 theme chromatography-connected 560:583 arg1 spectrometry 603:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry 536:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS) 536:627 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 7 40 theme PA-glucose 1277:1286 arg1 oligomer 1288:1295 the putative standard PA-glucose oligomer 1255:1295 the putative standard PA-glucose oligomer of the same m/z 1255:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 0 41 theme Mobility 18:25 arg1 Sections 43:50 Ion Mobility Collision Cross Sections 14:50 Ion Mobility Collision Cross Sections 14:50 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 3 42 theme ultraperformance 536:551 arg1 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 3 42 theme ultraperformance 536:551 arg1 spectrometry 603:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry 536:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS) 536:627 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 5 43 theme drift 781:785 arg1 times 787:791 collision drift times 771:791 collision drift times 771:791 A data set on collision drift times, retention times, and molecular mass was collected for these PA-oligosaccharides. 35997275 8 44 theme retention 1446:1454 arg1 GU 1462:1463 GU 1462:1463 GU 1462:1463 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 8 44 theme retention 1446:1454 arg1 time 1456:1459 normalized retention time 1435:1459 normalized retention time (GU) 1435:1464 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 8 45 theme m/z 1415:1417 arg1 database 1403:1410 the database 1399:1410 the database of m/z, CCS index, and normalized retention time (GU) 1399:1464 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 4 46 theme isomeric 741:748 arg1 pairs 750:754 isomeric pairs 741:754 isomeric pairs 741:754 To substantiate this methodology, we here examine 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs. 35997275 4 47 theme N-linked 705:712 arg1 oligosaccharides 714:729 71 pyridylaminated (PA-) N-linked oligosaccharides 680:729 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs 680:754 To substantiate this methodology, we here examine 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs. 35997275 4 47 theme N-linked 705:712 arg1 pairs 750:754 isomeric pairs 741:754 isomeric pairs 741:754 To substantiate this methodology, we here examine 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs. 35997275 0 48 theme Ion 14:16 arg1 Sections 43:50 Ion Mobility Collision Cross Sections 14:50 Ion Mobility Collision Cross Sections 14:50 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 4 49 theme pyridylaminated 683:697 arg1 oligosaccharides 714:729 71 pyridylaminated (PA-) N-linked oligosaccharides 680:729 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs 680:754 To substantiate this methodology, we here examine 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs. 35997275 4 49 theme pyridylaminated 683:697 arg1 pairs 750:754 isomeric pairs 741:754 isomeric pairs 741:754 To substantiate this methodology, we here examine 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs. 35997275 1 50 theme structure-function 221:238 arg1 relationships 240:252 structure-function relationships 221:252 structure-function relationships of glycans and glycoconjugates including biopharmaceuticals 221:312 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 1 50 theme structure-function 221:238 arg1 biopharmaceuticals 295:312 biopharmaceuticals 295:312 biopharmaceuticals 295:312 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 0 51 theme Cross 37:41 arg1 Sections 43:50 Ion Mobility Collision Cross Sections 14:50 Ion Mobility Collision Cross Sections 14:50 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 5 52 theme molecular 815:823 arg1 mass 825:828 molecular mass 815:828 molecular mass 815:828 A data set on collision drift times, retention times, and molecular mass was collected for these PA-oligosaccharides. 35997275 8 53 theme CCS 1420:1422 arg1 index 1424:1428 CCS index 1420:1428 CCS index 1420:1428 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 7 54 theme same 1304:1307 arg1 m/z 1309:1311 the same m/z 1300:1311 the same m/z 1300:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 0 55 theme Collision 27:35 arg1 Sections 43:50 Ion Mobility Collision Cross Sections 14:50 Ion Mobility Collision Cross Sections 14:50 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 6 56 theme glucose 1009:1015 arg1 oligomers 1017:1025 pyridylaminated α-1,6-linked glucose oligomers 980:1025 pyridylaminated α-1,6-linked glucose oligomers 980:1025 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 3 57 theme N-glycan 513:520 arg1 structures 522:531 N-glycan structures 513:531 N-glycan structures 513:531 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 4 58 dep pyridylaminated 683:697 arg1 PA- 700:702 PA- 700:702 PA- 700:702 To substantiate this methodology, we here examine 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs. 35997275 2 59 theme resolution 375:384 arg1 spectrometry 320:331 Mass spectrometry 315:331 Mass spectrometry 315:331 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 2 59 theme resolution 375:384 arg1 means 403:407 an excellent means 390:407 an excellent means of analyzing glycan structures 390:438 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 6 60 theme α-1,6-linked 996:1007 arg1 oligomers 1017:1025 pyridylaminated α-1,6-linked glucose oligomers 980:1025 pyridylaminated α-1,6-linked glucose oligomers 980:1025 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 5 61 theme data 759:762 arg1 set 764:766 A data set 757:766 A data set on collision drift times, retention times, and molecular mass 757:828 A data set on collision drift times, retention times, and molecular mass was collected for these PA-oligosaccharides. 35997275 4 62 link N-linked 705:712 arg1 oligosaccharides 714:729 71 pyridylaminated (PA-) N-linked oligosaccharides 680:729 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs 680:754 To substantiate this methodology, we here examine 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs. 35997275 4 62 link N-linked 705:712 arg1 pairs 750:754 isomeric pairs 741:754 isomeric pairs 741:754 To substantiate this methodology, we here examine 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs. 35997275 6 63 theme collision 1086:1094 arg1 CCS 1112:1114 CCS 1112:1114 CCS 1112:1114 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 6 63 theme collision 1086:1094 arg1 sections 1102:1109 collision cross sections 1086:1109 collision cross sections (CCS) 1086:1115 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 2 64 theme mass 370:373 arg1 resolution 375:384 mass resolution 370:384 mass resolution 370:384 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 6 65 theme cross 1096:1100 arg1 CCS 1112:1114 CCS 1112:1114 CCS 1112:1114 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 6 65 theme cross 1096:1100 arg1 sections 1102:1109 collision cross sections 1086:1109 collision cross sections (CCS) 1086:1115 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 8 66 theme N-linked 1373:1380 arg1 glycans 1382:1388 N-linked glycans 1373:1388 N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU) 1373:1464 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 6 67 theme observables 902:912 arg1 standardization 879:893 standardization 879:893 standardization of the observables 879:912 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 6 68 link α-1,6-linked 996:1007 arg1 oligomers 1017:1025 pyridylaminated α-1,6-linked glucose oligomers 980:1025 pyridylaminated α-1,6-linked glucose oligomers 980:1025 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 3 69 theme mobility 589:596 arg1 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 3 69 theme mobility 589:596 arg1 spectrometry 603:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry 536:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS) 536:627 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 8 70 theme structural 1350:1359 arg1 analysis 1361:1368 practical structural analysis 1340:1368 practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU) 1340:1464 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 0 71 from Oligosaccharides 127:142 arg1 Set 7:9 A Data Set 0:9 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 0:143 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 0 71 from Oligosaccharides 127:142 arg1 Times 88:92 Liquid Chromatography Retention Times 56:92 Liquid Chromatography Retention Times 56:92 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 0 71 from Oligosaccharides 127:142 arg1 Sections 43:50 Ion Mobility Collision Cross Sections 14:50 Ion Mobility Collision Cross Sections 14:50 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 3 72 theme precise 487:493 arg1 identification 495:508 rapid and precise identification 477:508 rapid and precise identification of N-glycan structures 477:531 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 8 73 theme normalized 1435:1444 arg1 GU 1462:1463 GU 1462:1463 GU 1462:1463 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 8 73 theme normalized 1435:1444 arg1 time 1456:1459 normalized retention time 1435:1459 normalized retention time (GU) 1435:1464 We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU). 35997275 3 74 theme ion 585:587 arg1 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 UPLC/IM-MS 617:626 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 3 74 theme ion 585:587 arg1 spectrometry 603:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry 536:614 ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS) 536:627 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 3 75 theme rapid 477:481 arg1 identification 495:508 rapid and precise identification 477:508 rapid and precise identification of N-glycan structures 477:531 We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). 35997275 1 76 theme glycans 257:263 arg1 relationships 240:252 structure-function relationships 221:252 structure-function relationships of glycans and glycoconjugates including biopharmaceuticals 221:312 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 1 76 theme glycans 257:263 arg1 biopharmaceuticals 295:312 biopharmaceuticals 295:312 biopharmaceuticals 295:312 Determination of the glycan structure is an essential step in understanding structure-function relationships of glycans and glycoconjugates including biopharmaceuticals. 35997275 0 77 theme Sections 43:50 arg1 Set 7:9 A Data Set 0:9 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 0:143 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 0 77 theme Sections 43:50 arg1 Times 88:92 Liquid Chromatography Retention Times 56:92 Liquid Chromatography Retention Times 56:92 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 0 77 theme Sections 43:50 arg1 Sections 43:50 Ion Mobility Collision Cross Sections 14:50 Ion Mobility Collision Cross Sections 14:50 A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides. 35997275 6 78 theme pyridylaminated 980:994 arg1 oligomers 1017:1025 pyridylaminated α-1,6-linked glucose oligomers 980:1025 pyridylaminated α-1,6-linked glucose oligomers 980:1025 For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). 35997275 7 79 theme m/z 1309:1311 arg1 oligomer 1288:1295 the putative standard PA-glucose oligomer 1255:1295 the putative standard PA-glucose oligomer of the same m/z 1255:1311 To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. 35997275 2 80 theme excellent 393:401 arg1 spectrometry 320:331 Mass spectrometry 315:331 Mass spectrometry 315:331 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 2 80 theme excellent 393:401 arg1 means 403:407 an excellent means 390:407 an excellent means of analyzing glycan structures 390:438 Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. 35997275 5 81 theme retention 794:802 arg1 times 804:808 retention times 794:808 retention times 794:808 A data set on collision drift times, retention times, and molecular mass was collected for these PA-oligosaccharides. 35247693 5 0 theme flavone 825:831 arg1 enzyme 849:854 a key enzyme 843:854 a key enzyme of tricin biosynthesis 843:877 By inhibiting flavone synthase, a key enzyme of tricin biosynthesis, PDCA decreased total lignin content and improved saccharification without affecting root growth. 35247693 5 0 theme flavone 825:831 arg1 synthase 833:840 flavone synthase 825:840 flavone synthase 825:840 By inhibiting flavone synthase, a key enzyme of tricin biosynthesis, PDCA decreased total lignin content and improved saccharification without affecting root growth. 35247693 5 1 theme root 964:967 arg1 growth 969:974 root growth 964:974 root growth 964:974 By inhibiting flavone synthase, a key enzyme of tricin biosynthesis, PDCA decreased total lignin content and improved saccharification without affecting root growth. 35247693 6 2 theme enzymatic 1076:1084 arg1 inhibitors 1086:1095 enzymatic inhibitors 1076:1095 enzymatic inhibitors 1076:1095 PDCA was three-fold more effective than MDCA, suggesting that controlling lignin biosynthesis with enzymatic inhibitors may be an attractive strategy to improve biomass saccharification. 35247693 3 3 theme methylenedioxy 468:481 arg1 acid 492:495 [3,4-(methylenedioxy)cinnamic acid 462:495 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] 448:542 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 4 4 theme hydroxycinnamoyl-CoA 646:665 arg1 enzyme 681:686 a key enzyme 675:686 a key enzyme of phenylpropanoid pathway 675:713 By inhibiting hydroxycinnamoyl-CoA ligase, a key enzyme of phenylpropanoid pathway, MDCA decreased the lignin content and improved saccharification, but it decreased root growth. 35247693 4 4 theme hydroxycinnamoyl-CoA 646:665 arg1 ligase 667:672 hydroxycinnamoyl-CoA ligase 646:672 hydroxycinnamoyl-CoA ligase 646:672 By inhibiting hydroxycinnamoyl-CoA ligase, a key enzyme of phenylpropanoid pathway, MDCA decreased the lignin content and improved saccharification, but it decreased root growth. 35247693 4 5 theme root 798:801 arg1 growth 803:808 root growth 798:808 root growth 798:808 By inhibiting hydroxycinnamoyl-CoA ligase, a key enzyme of phenylpropanoid pathway, MDCA decreased the lignin content and improved saccharification, but it decreased root growth. 35247693 3 6 from findings 565:572 arg1 growth 582:587 root growth 577:587 root growth 577:587 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 3 6 from findings 565:572 arg1 composition 597:607 lignin composition 590:607 lignin composition 590:607 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 3 6 from findings 565:572 arg1 saccharification 614:629 saccharification 614:629 saccharification 614:629 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 3 7 theme lignin 590:595 arg1 composition 597:607 lignin composition 590:607 lignin composition 590:607 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 5 8 theme total 895:899 arg1 content 908:914 total lignin content 895:914 total lignin content 895:914 By inhibiting flavone synthase, a key enzyme of tricin biosynthesis, PDCA decreased total lignin content and improved saccharification without affecting root growth. 35247693 3 9 theme root 577:580 arg1 growth 582:587 root growth 577:587 root growth 577:587 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 2 10 theme tricin 431:436 arg1 pathways 438:445 the lignin and tricin pathways 416:445 pathways 438:445 Using maize seedlings grown hydroponically for 24 h, we conducted a quick non-transgenic approach with five enzyme inhibitors of the lignin and tricin pathways. 35247693 1 11 theme genetic-based 196:208 arg1 engineering 220:230 genetic-based metabolic engineering 196:230 genetic-based metabolic engineering 196:230 Lignin is a technological bottleneck to convert polysaccharides into fermentable sugars, and different strategies of genetic-based metabolic engineering have been applied to improve biomass saccharification. 35247693 6 12 theme lignin 1051:1056 arg1 biosynthesis 1058:1069 lignin biosynthesis 1051:1069 lignin biosynthesis with enzymatic inhibitors 1051:1095 PDCA was three-fold more effective than MDCA, suggesting that controlling lignin biosynthesis with enzymatic inhibitors may be an attractive strategy to improve biomass saccharification. 35247693 3 13 theme [3,4- 462:466 arg1 acid 492:495 [3,4-(methylenedioxy)cinnamic acid 462:495 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] 448:542 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 1 14 theme technological 91:103 arg1 Lignin 79:84 Lignin 79:84 Lignin 79:84 Lignin is a technological bottleneck to convert polysaccharides into fermentable sugars, and different strategies of genetic-based metabolic engineering have been applied to improve biomass saccharification. 35247693 1 14 theme technological 91:103 arg1 bottleneck 105:114 a technological bottleneck 89:114 a technological bottleneck to convert polysaccharides into fermentable sugars 89:165 Lignin is a technological bottleneck to convert polysaccharides into fermentable sugars, and different strategies of genetic-based metabolic engineering have been applied to improve biomass saccharification. 35247693 1 15 theme metabolic 210:218 arg1 engineering 220:230 genetic-based metabolic engineering 196:230 genetic-based metabolic engineering 196:230 Lignin is a technological bottleneck to convert polysaccharides into fermentable sugars, and different strategies of genetic-based metabolic engineering have been applied to improve biomass saccharification. 35247693 0 16 theme tricin 11:16 arg1 biosynthesis 18:29 tricin biosynthesis 11:29 tricin biosynthesis 11:29 Inhibiting tricin biosynthesis improves maize lignocellulose saccharification. 35247693 2 17 theme non-transgenic 361:374 arg1 approach 376:383 a quick non-transgenic approach 353:383 a quick non-transgenic approach with five enzyme inhibitors of the lignin and tricin pathways 353:445 Using maize seedlings grown hydroponically for 24 h, we conducted a quick non-transgenic approach with five enzyme inhibitors of the lignin and tricin pathways. 35247693 1 18 theme engineering 220:230 arg1 strategies 182:191 different strategies 172:191 different strategies of genetic-based metabolic engineering 172:230 Lignin is a technological bottleneck to convert polysaccharides into fermentable sugars, and different strategies of genetic-based metabolic engineering have been applied to improve biomass saccharification. 35247693 5 19 theme tricin 859:864 arg1 biosynthesis 866:877 tricin biosynthesis 859:877 tricin biosynthesis 859:877 By inhibiting flavone synthase, a key enzyme of tricin biosynthesis, PDCA decreased total lignin content and improved saccharification without affecting root growth. 35247693 2 20 theme quick 355:359 arg1 approach 376:383 a quick non-transgenic approach 353:383 a quick non-transgenic approach with five enzyme inhibitors of the lignin and tricin pathways 353:445 Using maize seedlings grown hydroponically for 24 h, we conducted a quick non-transgenic approach with five enzyme inhibitors of the lignin and tricin pathways. 35247693 6 21 theme biomass 1138:1144 arg1 saccharification 1146:1161 biomass saccharification 1138:1161 biomass saccharification 1138:1161 PDCA was three-fold more effective than MDCA, suggesting that controlling lignin biosynthesis with enzymatic inhibitors may be an attractive strategy to improve biomass saccharification. 35247693 5 22 theme biosynthesis 866:877 arg1 enzyme 849:854 a key enzyme 843:854 a key enzyme of tricin biosynthesis 843:877 By inhibiting flavone synthase, a key enzyme of tricin biosynthesis, PDCA decreased total lignin content and improved saccharification without affecting root growth. 35247693 5 22 theme biosynthesis 866:877 arg1 synthase 833:840 flavone synthase 825:840 flavone synthase 825:840 By inhibiting flavone synthase, a key enzyme of tricin biosynthesis, PDCA decreased total lignin content and improved saccharification without affecting root growth. 35247693 3 23 theme interesting 553:563 arg1 findings 565:572 interesting findings 553:572 interesting findings on root growth, lignin composition, and saccharification 553:629 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 3 24 theme 2,4-pyridinedicarboxylic 507:530 arg1 acid 532:535 2,4-pyridinedicarboxylic acid 507:535 2,4-pyridinedicarboxylic acid 507:535 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 0 25 theme lignocellulose 46:59 arg1 saccharification 61:76 maize lignocellulose saccharification 40:76 maize lignocellulose saccharification 40:76 Inhibiting tricin biosynthesis improves maize lignocellulose saccharification. 35247693 2 26 with approach 376:383 arg1 inhibitors 402:411 five enzyme inhibitors 390:411 five enzyme inhibitors of the lignin and tricin pathways 390:445 Using maize seedlings grown hydroponically for 24 h, we conducted a quick non-transgenic approach with five enzyme inhibitors of the lignin and tricin pathways. 35247693 4 27 theme pathway 707:713 arg1 enzyme 681:686 a key enzyme 675:686 a key enzyme of phenylpropanoid pathway 675:713 By inhibiting hydroxycinnamoyl-CoA ligase, a key enzyme of phenylpropanoid pathway, MDCA decreased the lignin content and improved saccharification, but it decreased root growth. 35247693 4 27 theme pathway 707:713 arg1 ligase 667:672 hydroxycinnamoyl-CoA ligase 646:672 hydroxycinnamoyl-CoA ligase 646:672 By inhibiting hydroxycinnamoyl-CoA ligase, a key enzyme of phenylpropanoid pathway, MDCA decreased the lignin content and improved saccharification, but it decreased root growth. 35247693 0 28 theme maize 40:44 arg1 saccharification 61:76 maize lignocellulose saccharification 40:76 maize lignocellulose saccharification 40:76 Inhibiting tricin biosynthesis improves maize lignocellulose saccharification. 35247693 5 29 theme lignin 901:906 arg1 content 908:914 total lignin content 895:914 total lignin content 895:914 By inhibiting flavone synthase, a key enzyme of tricin biosynthesis, PDCA decreased total lignin content and improved saccharification without affecting root growth. 35247693 3 30 theme MDCA 498:501 arg1 compounds 452:460 Two compounds 448:460 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] 448:542 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 5 31 theme key 845:847 arg1 enzyme 849:854 a key enzyme 843:854 a key enzyme of tricin biosynthesis 843:877 By inhibiting flavone synthase, a key enzyme of tricin biosynthesis, PDCA decreased total lignin content and improved saccharification without affecting root growth. 35247693 5 31 theme key 845:847 arg1 synthase 833:840 flavone synthase 825:840 flavone synthase 825:840 By inhibiting flavone synthase, a key enzyme of tricin biosynthesis, PDCA decreased total lignin content and improved saccharification without affecting root growth. 35247693 6 32 theme attractive 1107:1116 arg1 strategy 1118:1125 an attractive strategy 1104:1125 an attractive strategy to improve biomass saccharification 1104:1161 PDCA was three-fold more effective than MDCA, suggesting that controlling lignin biosynthesis with enzymatic inhibitors may be an attractive strategy to improve biomass saccharification. 35247693 3 33 theme cinnamic 483:490 arg1 acid 492:495 [3,4-(methylenedioxy)cinnamic acid 462:495 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] 448:542 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 2 34 theme enzyme 395:400 arg1 inhibitors 402:411 five enzyme inhibitors 390:411 five enzyme inhibitors of the lignin and tricin pathways 390:445 Using maize seedlings grown hydroponically for 24 h, we conducted a quick non-transgenic approach with five enzyme inhibitors of the lignin and tricin pathways. 35247693 3 35 dep compounds 452:460 arg1 acid 492:495 [3,4-(methylenedioxy)cinnamic acid 462:495 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] 448:542 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 1 36 theme fermentable 148:158 arg1 sugars 160:165 fermentable sugars 148:165 fermentable sugars 148:165 Lignin is a technological bottleneck to convert polysaccharides into fermentable sugars, and different strategies of genetic-based metabolic engineering have been applied to improve biomass saccharification. 35247693 6 37 with biosynthesis 1058:1069 arg1 inhibitors 1086:1095 enzymatic inhibitors 1076:1095 enzymatic inhibitors 1076:1095 PDCA was three-fold more effective than MDCA, suggesting that controlling lignin biosynthesis with enzymatic inhibitors may be an attractive strategy to improve biomass saccharification. 35247693 3 38 theme acid 532:535 arg1 compounds 452:460 Two compounds 448:460 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] 448:542 Two compounds [3,4-(methylenedioxy)cinnamic acid: MDCA and 2,4-pyridinedicarboxylic acid: PDCA] revealed interesting findings on root growth, lignin composition, and saccharification. 35247693 1 39 theme biomass 261:267 arg1 saccharification 269:284 biomass saccharification 261:284 biomass saccharification 261:284 Lignin is a technological bottleneck to convert polysaccharides into fermentable sugars, and different strategies of genetic-based metabolic engineering have been applied to improve biomass saccharification. 35247693 4 40 theme lignin 735:740 arg1 content 742:748 the lignin content 731:748 the lignin content 731:748 By inhibiting hydroxycinnamoyl-CoA ligase, a key enzyme of phenylpropanoid pathway, MDCA decreased the lignin content and improved saccharification, but it decreased root growth. 35247693 4 41 theme phenylpropanoid 691:705 arg1 pathway 707:713 phenylpropanoid pathway 691:713 phenylpropanoid pathway 691:713 By inhibiting hydroxycinnamoyl-CoA ligase, a key enzyme of phenylpropanoid pathway, MDCA decreased the lignin content and improved saccharification, but it decreased root growth. 35247693 2 42 theme lignin 420:425 arg1 pathways 438:445 the lignin and tricin pathways 416:445 pathways 438:445 Using maize seedlings grown hydroponically for 24 h, we conducted a quick non-transgenic approach with five enzyme inhibitors of the lignin and tricin pathways. 35247693 2 43 theme pathways 438:445 arg1 inhibitors 402:411 five enzyme inhibitors 390:411 five enzyme inhibitors of the lignin and tricin pathways 390:445 Using maize seedlings grown hydroponically for 24 h, we conducted a quick non-transgenic approach with five enzyme inhibitors of the lignin and tricin pathways. 35247693 4 44 theme key 677:679 arg1 enzyme 681:686 a key enzyme 675:686 a key enzyme of phenylpropanoid pathway 675:713 By inhibiting hydroxycinnamoyl-CoA ligase, a key enzyme of phenylpropanoid pathway, MDCA decreased the lignin content and improved saccharification, but it decreased root growth. 35247693 4 44 theme key 677:679 arg1 ligase 667:672 hydroxycinnamoyl-CoA ligase 646:672 hydroxycinnamoyl-CoA ligase 646:672 By inhibiting hydroxycinnamoyl-CoA ligase, a key enzyme of phenylpropanoid pathway, MDCA decreased the lignin content and improved saccharification, but it decreased root growth. 35247693 2 45 theme maize 293:297 arg1 seedlings 299:307 maize seedlings 293:307 maize seedlings grown hydroponically for 24 h 293:337 Using maize seedlings grown hydroponically for 24 h, we conducted a quick non-transgenic approach with five enzyme inhibitors of the lignin and tricin pathways. 35247693 1 46 theme different 172:180 arg1 strategies 182:191 different strategies 172:191 different strategies of genetic-based metabolic engineering 172:230 Lignin is a technological bottleneck to convert polysaccharides into fermentable sugars, and different strategies of genetic-based metabolic engineering have been applied to improve biomass saccharification. 36013754 0 0 theme Nanoparticles 82:94 arg1 Activities 61:70 Antibacterial Activities 47:70 Antibacterial Activities 47:70 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 0 0 theme Nanoparticles 82:94 arg1 Conditions 10:19 Synthetic Conditions 0:19 Synthetic Conditions 0:19 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 0 0 theme Nanoparticles 82:94 arg1 Properties 31:40 Physical Properties 22:40 Physical Properties 22:40 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 3 1 theme conditions 663:672 arg1 course 689:694 reaction time course 675:694 reaction time course 675:694 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 1 theme conditions 663:672 arg1 concentration 722:734 reagent concentration 714:734 reagent concentration 714:734 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 1 theme conditions 663:672 arg1 conditions 663:672 optimal synthetic conditions 645:672 optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 645:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 1 theme conditions 663:672 arg1 temperature 697:707 temperature 697:707 temperature 697:707 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 1 theme conditions 663:672 arg1 set 638:640 a unique set 629:640 a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 629:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 0 2 with Properties 31:40 arg1 Exopolysaccharides 101:118 Exopolysaccharides 101:118 Exopolysaccharides of a Medicinal Fungus 101:140 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 1 3 theme attractive 171:180 arg1 biomacromolecules 196:212 attractive and promising biomacromolecules 171:212 attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions 171:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 1 3 theme attractive 171:180 arg1 polysaccharides 151:165 Natural polysaccharides 143:165 Natural polysaccharides 143:165 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 4 4 dep coli 955:958 arg1 Gram- 961:965 Gram- 961:965 Gram- 961:965 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 3 5 theme Ag 771:772 arg1 distributions 782:794 Ag NP size distributions 771:794 Ag NP size distributions 771:794 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 0 6 theme Silver 75:80 arg1 Nanoparticles 82:94 Silver Nanoparticles 75:94 Silver Nanoparticles 75:94 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 5 7 with success 1126:1132 arg1 application 1240:1250 the potential antibacterial application 1212:1250 the potential antibacterial application of EPS-coated Ag NPs 1212:1271 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 5 7 with success 1126:1132 arg1 fractions 1198:1206 all three EPS fractions 1184:1206 all three EPS fractions 1184:1206 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 4 8 theme Ag 801:802 arg1 NPs 804:806 The Ag NPs 797:806 The Ag NPs synthesized with the EPS-1 fraction 797:842 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 3 9 theme NP 774:775 arg1 distributions 782:794 Ag NP size distributions 771:794 Ag NP size distributions 771:794 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 2 10 theme medicinal 497:505 arg1 fungus 507:512 a medicinal fungus 495:512 a medicinal fungus known as Cs-HK1 495:528 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 3 11 theme optimal 645:651 arg1 concentration 722:734 reagent concentration 714:734 reagent concentration 714:734 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 11 theme optimal 645:651 arg1 conditions 663:672 optimal synthetic conditions 645:672 optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 645:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 11 theme optimal 645:651 arg1 temperature 697:707 temperature 697:707 temperature 697:707 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 11 theme optimal 645:651 arg1 course 689:694 reaction time course 675:694 reaction time course 675:694 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 2 12 theme chemical 556:563 arg1 composition 565:575 their chemical composition 550:575 their chemical composition 550:575 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 4 13 dep aureus 987:992 arg1 Gram+ 995:999 Gram+ 995:999 Gram+ 995:999 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 5 14 theme scheme 1141:1146 arg1 success 1126:1132 the success 1122:1132 the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs 1122:1271 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 5 15 theme potential 1216:1224 arg1 application 1240:1250 the potential antibacterial application 1212:1250 the potential antibacterial application of EPS-coated Ag NPs 1212:1271 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 3 16 theme time 684:687 arg1 conditions 663:672 optimal synthetic conditions 645:672 optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 645:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 16 theme time 684:687 arg1 course 689:694 reaction time course 675:694 reaction time course 675:694 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 4 17 with size 870:873 arg1 MIC 1044:1046 MIC 1044:1046 MIC 1044:1046 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 17 with size 870:873 arg1 concentration 1029:1041 a minimal inhibitory concentration 1008:1041 a minimal inhibitory concentration (MIC) of 0.2 mg/mL 1008:1060 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 1 18 theme broad 278:282 arg1 spectrum 284:291 a broad spectrum 276:291 a broad spectrum of useful functions 276:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 5 19 theme EPS 1194:1196 arg1 fractions 1198:1206 all three EPS fractions 1184:1206 all three EPS fractions 1184:1206 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 0 20 with Activities 61:70 arg1 Exopolysaccharides 101:118 Exopolysaccharides 101:118 Exopolysaccharides of a Medicinal Fungus 101:140 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 4 21 contain had 844:846 arg2 size 870:873 the smallest particle size 848:873 the smallest particle size (~160 nm) 848:883 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 21 contain had 844:846 arg1 NPs 804:806 The Ag NPs 797:806 The Ag NPs synthesized with the EPS-1 fraction 797:842 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 21 contain had 844:846 arg2 activities 924:933 the most significant antibacterial activities 889:933 the most significant antibacterial activities 889:933 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 21 contain had 844:846 arg2 nm 881:882 ~160 nm 876:882 ~160 nm 876:882 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 1 22 theme promising 186:194 arg1 biomacromolecules 196:212 attractive and promising biomacromolecules 171:212 attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions 171:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 1 22 theme promising 186:194 arg1 polysaccharides 151:165 Natural polysaccharides 143:165 Natural polysaccharides 143:165 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 2 23 from variations 536:545 arg1 composition 565:575 their chemical composition 550:575 their chemical composition 550:575 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 2 23 from variations 536:545 arg1 weight 591:596 molecular weight 581:596 molecular weight 581:596 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 2 24 theme NPs 397:399 arg1 conditions 356:365 the synthetic conditions 342:365 the synthetic conditions 342:365 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 2 24 theme NPs 397:399 arg1 properties 380:389 physical properties 371:389 physical properties of Ag NPs 371:399 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 3 25 theme reaction 675:682 arg1 conditions 663:672 optimal synthetic conditions 645:672 optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 645:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 25 theme reaction 675:682 arg1 course 689:694 reaction time course 675:694 reaction time course 675:694 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 2 26 theme Ag 394:395 arg1 NPs 397:399 Ag NPs 394:399 Ag NPs 394:399 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 0 27 theme Synthetic 0:8 arg1 Conditions 10:19 Synthetic Conditions 0:19 Synthetic Conditions 0:19 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 2 28 theme molecular 581:589 arg1 weight 591:596 molecular weight 581:596 molecular weight 581:596 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 4 29 with activities 924:933 arg1 MIC 1044:1046 MIC 1044:1046 MIC 1044:1046 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 29 with activities 924:933 arg1 concentration 1029:1041 a minimal inhibitory concentration 1008:1041 a minimal inhibitory concentration (MIC) of 0.2 mg/mL 1008:1060 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 30 theme minimal 1010:1016 arg1 MIC 1044:1046 MIC 1044:1046 MIC 1044:1046 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 30 theme minimal 1010:1016 arg1 concentration 1029:1041 a minimal inhibitory concentration 1008:1041 a minimal inhibitory concentration (MIC) of 0.2 mg/mL 1008:1060 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 0 31 theme Physical 22:29 arg1 Properties 31:40 Physical Properties 22:40 Physical Properties 22:40 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 0 32 theme Fungus 135:140 arg1 Exopolysaccharides 101:118 Exopolysaccharides 101:118 Exopolysaccharides of a Medicinal Fungus 101:140 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 4 33 theme significant 898:908 arg1 activities 924:933 the most significant antibacterial activities 889:933 the most significant antibacterial activities 889:933 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 1 34 theme green 222:226 arg1 synthesis 228:236 the green synthesis 218:236 the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions 218:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 5 35 theme antibacterial 1226:1238 arg1 application 1240:1250 the potential antibacterial application 1212:1250 the potential antibacterial application of EPS-coated Ag NPs 1212:1271 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 1 36 theme useful 296:301 arg1 functions 303:311 useful functions 296:311 useful functions 296:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 0 37 theme Medicinal 125:133 arg1 Fungus 135:140 a Medicinal Fungus 123:140 a Medicinal Fungus 123:140 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 3 38 theme EPS 611:613 arg1 fractions 615:623 the EPS fractions 607:623 the EPS fractions 607:623 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 4 39 theme inhibitory 1018:1027 arg1 MIC 1044:1046 MIC 1044:1046 MIC 1044:1046 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 39 theme inhibitory 1018:1027 arg1 concentration 1029:1041 a minimal inhibitory concentration 1008:1041 a minimal inhibitory concentration (MIC) of 0.2 mg/mL 1008:1060 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 5 40 theme scheme 1172:1177 arg1 scheme 1141:1146 the scheme 1137:1146 the scheme of this green synthesis scheme 1137:1177 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 1 41 theme functions 303:311 arg1 spectrum 284:291 a broad spectrum 276:291 a broad spectrum of useful functions 276:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 3 42 theme distributions 782:794 arg1 range 762:766 a specific range 751:766 a specific range of Ag NP size distributions 751:794 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 4 43 theme antibacterial 910:922 arg1 activities 924:933 the most significant antibacterial activities 889:933 the most significant antibacterial activities 889:933 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 44 theme particle 861:868 arg1 nm 881:882 ~160 nm 876:882 ~160 nm 876:882 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 44 theme particle 861:868 arg1 size 870:873 the smallest particle size 848:873 the smallest particle size (~160 nm) 848:883 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 5 45 theme EPS-coated 1255:1264 arg1 NPs 1269:1271 EPS-coated Ag NPs 1255:1271 EPS-coated Ag NPs 1255:1271 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 1 46 theme silver 241:246 arg1 nanoparticles 248:260 silver nanoparticles 241:260 silver nanoparticles (Ag NPs) with a broad spectrum of useful functions 241:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 1 46 theme silver 241:246 arg1 NPs 266:268 Ag NPs 263:268 Ag NPs 263:268 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 0 47 theme Antibacterial 47:59 arg1 Activities 61:70 Antibacterial Activities 47:70 Antibacterial Activities 47:70 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 4 48 theme EPS-1 829:833 arg1 fraction 835:842 the EPS-1 fraction 825:842 the EPS-1 fraction 825:842 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 5 49 theme Ag 1266:1267 arg1 NPs 1269:1271 EPS-coated Ag NPs 1255:1271 EPS-coated Ag NPs 1255:1271 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 2 50 theme synthetic 346:354 arg1 conditions 356:365 the synthetic conditions 342:365 the synthetic conditions 342:365 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 5 51 theme synthesis 1162:1170 arg1 scheme 1172:1177 this green synthesis scheme 1151:1177 this green synthesis scheme 1151:1177 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 3 52 theme reagent 714:720 arg1 concentration 722:734 reagent concentration 714:734 reagent concentration 714:734 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 52 theme reagent 714:720 arg1 conditions 663:672 optimal synthetic conditions 645:672 optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 645:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 4 53 theme smallest 852:859 arg1 nm 881:882 ~160 nm 876:882 ~160 nm 876:882 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 53 theme smallest 852:859 arg1 size 870:873 the smallest particle size 848:873 the smallest particle size (~160 nm) 848:883 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 3 54 theme unique 631:636 arg1 course 689:694 reaction time course 675:694 reaction time course 675:694 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 54 theme unique 631:636 arg1 concentration 722:734 reagent concentration 714:734 reagent concentration 714:734 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 54 theme unique 631:636 arg1 conditions 663:672 optimal synthetic conditions 645:672 optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 645:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 54 theme unique 631:636 arg1 temperature 697:707 temperature 697:707 temperature 697:707 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 54 theme unique 631:636 arg1 set 638:640 a unique set 629:640 a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 629:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 0 55 with Conditions 10:19 arg1 Exopolysaccharides 101:118 Exopolysaccharides 101:118 Exopolysaccharides of a Medicinal Fungus 101:140 Synthetic Conditions, Physical Properties, and Antibacterial Activities of Silver Nanoparticles with Exopolysaccharides of a Medicinal Fungus. 36013754 5 56 theme NPs 1269:1271 arg1 application 1240:1250 the potential antibacterial application 1212:1250 the potential antibacterial application of EPS-coated Ag NPs 1212:1271 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 5 56 theme NPs 1269:1271 arg1 fractions 1198:1206 all three EPS fractions 1184:1206 all three EPS fractions 1184:1206 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 36013754 3 57 dep conditions 663:672 arg1 concentration 722:734 reagent concentration 714:734 reagent concentration 714:734 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 57 dep conditions 663:672 arg1 conditions 663:672 optimal synthetic conditions 645:672 optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 645:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 57 dep conditions 663:672 arg1 temperature 697:707 temperature 697:707 temperature 697:707 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 57 dep conditions 663:672 arg1 course 689:694 reaction time course 675:694 reaction time course 675:694 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 1 58 theme nanoparticles 248:260 arg1 synthesis 228:236 the green synthesis 218:236 the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions 218:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 4 59 theme mg/mL 1056:1060 arg1 MIC 1044:1046 MIC 1044:1046 MIC 1044:1046 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 4 59 theme mg/mL 1056:1060 arg1 concentration 1029:1041 a minimal inhibitory concentration 1008:1041 a minimal inhibitory concentration (MIC) of 0.2 mg/mL 1008:1060 The Ag NPs synthesized with the EPS-1 fraction had the smallest particle size (~160 nm) and the most significant antibacterial activities against Escherichia coli (Gram-) and Staphylococcus aureus (Gram+), with a minimal inhibitory concentration (MIC) of 0.2 mg/mL on E. coli and 0.075 mg/mL on S. aureus. 36013754 1 60 theme Natural 143:149 arg1 biomacromolecules 196:212 attractive and promising biomacromolecules 171:212 attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions 171:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 1 60 theme Natural 143:149 arg1 polysaccharides 151:165 Natural polysaccharides 143:165 Natural polysaccharides 143:165 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 3 61 theme size 777:780 arg1 distributions 782:794 Ag NP size distributions 771:794 Ag NP size distributions 771:794 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 62 theme specific 753:760 arg1 range 762:766 a specific range 751:766 a specific range of Ag NP size distributions 751:794 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 2 63 theme exopolysaccharide 426:442 arg1 EPS-3 476:480 EPS-3 476:480 EPS-3 476:480 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 2 63 theme exopolysaccharide 426:442 arg1 fractions 413:421 three fractions 407:421 three fractions of exopolysaccharide (EPS) 407:448 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 2 63 theme exopolysaccharide 426:442 arg1 EPS-2 465:469 EPS-2 465:469 EPS-2 465:469 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 2 63 theme exopolysaccharide 426:442 arg1 EPS-1 458:462 EPS-1 458:462 EPS-1 458:462 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 3 64 contain had 625:627 arg2 conditions 663:672 optimal synthetic conditions 645:672 optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 645:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 64 contain had 625:627 arg2 temperature 697:707 temperature 697:707 temperature 697:707 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 64 contain had 625:627 arg2 set 638:640 a unique set 629:640 a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 629:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 64 contain had 625:627 arg1 fractions 615:623 the EPS fractions 607:623 the EPS fractions 607:623 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 64 contain had 625:627 arg2 course 689:694 reaction time course 675:694 reaction time course 675:694 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 64 contain had 625:627 arg2 concentration 722:734 reagent concentration 714:734 reagent concentration 714:734 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 64 contain had 625:627 arg1 Each 599:602 Each 599:602 Each 599:602 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 1 65 theme Ag 263:264 arg1 nanoparticles 248:260 silver nanoparticles 241:260 silver nanoparticles (Ag NPs) with a broad spectrum of useful functions 241:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 1 65 theme Ag 263:264 arg1 NPs 266:268 Ag NPs 263:268 Ag NPs 263:268 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 3 66 theme synthetic 653:661 arg1 concentration 722:734 reagent concentration 714:734 reagent concentration 714:734 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 66 theme synthetic 653:661 arg1 conditions 663:672 optimal synthetic conditions 645:672 optimal synthetic conditions (reaction time course, temperature, and reagent concentration) 645:735 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 66 theme synthetic 653:661 arg1 temperature 697:707 temperature 697:707 temperature 697:707 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 3 66 theme synthetic 653:661 arg1 course 689:694 reaction time course 675:694 reaction time course 675:694 Each of the EPS fractions had a unique set of optimal synthetic conditions (reaction time course, temperature, and reagent concentration), resulting in a specific range of Ag NP size distributions. 36013754 1 67 with nanoparticles 248:260 arg1 spectrum 284:291 a broad spectrum 276:291 a broad spectrum of useful functions 276:311 Natural polysaccharides are attractive and promising biomacromolecules for the green synthesis of silver nanoparticles (Ag NPs) with a broad spectrum of useful functions. 36013754 2 68 theme physical 371:378 arg1 properties 380:389 physical properties 371:389 physical properties of Ag NPs 371:399 This study aims to evaluate the synthetic conditions and physical properties of Ag NPs using three fractions of exopolysaccharide (EPS), namely EPS-1, EPS-2, and EPS-3, produced by a medicinal fungus known as Cs-HK1, with variations in their chemical composition and molecular weight. 36013754 5 69 theme green 1156:1160 arg1 scheme 1172:1177 this green synthesis scheme 1151:1177 this green synthesis scheme 1151:1177 The results proved the success of the scheme of this green synthesis scheme with all three EPS fractions and the potential antibacterial application of EPS-coated Ag NPs. 35681391 9 0 theme acid 863:866 arg1 content 868:874 Propionic acid content 853:874 Propionic acid content in women 853:883 Propionic acid content in women was significantly increased after DOP treatment. 35681391 1 1 from impact 166:171 arg1 microbiota 188:197 healthy gut microbiota 176:197 healthy gut microbiota 176:197 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 6 2 theme human 588:592 arg1 microbiota 594:603 human microbiota 588:603 human microbiota 588:603 16S rDNA sequencing was used to analyze the diversity of human microbiota. 35681391 10 3 theme correlation 947:957 arg1 analysis 959:966 the correlation analysis 943:966 the correlation analysis 943:966 Finally, the correlation analysis revealed that DOP was beneficial to the microbiota of both men and women. 35681391 8 4 theme relative 781:788 arg1 abundance 790:798 the relative abundance 777:798 the relative abundance of benign microbiota 777:819 DOP can increase the relative abundance of benign microbiota and decrease the harmful types. 35681391 7 5 theme average 667:673 arg1 weight 685:690 an average molecular weight 664:690 an average molecular weight of 277 kDa and 1318 Da 664:713 The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. 35681391 11 6 theme health 1093:1098 arg1 DOP 1084:1086 DOP 1084:1086 DOP 1084:1086 It can be concluded from the results that DOP is a health supplement suitable for humans, and especially women. 35681391 11 6 theme health 1093:1098 arg1 supplement 1100:1109 a health supplement 1091:1109 a health supplement suitable for humans, and especially women 1091:1151 It can be concluded from the results that DOP is a health supplement suitable for humans, and especially women. 35681391 7 7 dep contained 634:642 arg1 weight 685:690 an average molecular weight 664:690 an average molecular weight of 277 kDa and 1318 Da 664:713 The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. 35681391 7 7 dep contained 634:642 arg1 mainly 720:725 mainly 720:725 mainly 720:725 The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. 35681391 7 7 dep contained 634:642 arg1 composed 727:734 composed 727:734 composed of mannose and glucose 727:757 The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. 35681391 7 8 theme molecular 675:683 arg1 weight 685:690 an average molecular weight 664:690 an average molecular weight of 277 kDa and 1318 Da 664:713 The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. 35681391 8 9 theme benign 803:808 arg1 microbiota 810:819 benign microbiota 803:819 benign microbiota 803:819 DOP can increase the relative abundance of benign microbiota and decrease the harmful types. 35681391 5 10 theme Gas 472:474 arg1 chromatography 476:489 Gas chromatography 472:489 Gas chromatography 472:489 Gas chromatography was used to detect the content of SCFA. 35681391 1 11 theme specific 157:164 arg1 impact 166:171 its specific impact 153:171 its specific impact on healthy gut microbiota 153:197 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 6 12 theme 16S 531:533 arg1 sequencing 540:549 16S rDNA sequencing 531:549 16S rDNA sequencing 531:549 16S rDNA sequencing was used to analyze the diversity of human microbiota. 35681391 11 13 theme suitable 1111:1118 arg1 DOP 1084:1086 DOP 1084:1086 DOP 1084:1086 It can be concluded from the results that DOP is a health supplement suitable for humans, and especially women. 35681391 11 13 theme suitable 1111:1118 arg1 supplement 1100:1109 a health supplement 1091:1109 a health supplement suitable for humans, and especially women 1091:1151 It can be concluded from the results that DOP is a health supplement suitable for humans, and especially women. 35681391 0 14 theme Dendrobium 0:9 arg1 Polysaccharides 22:36 Dendrobium officinale Polysaccharides 0:36 Dendrobium officinale Polysaccharides 0:36 Dendrobium officinale Polysaccharides Better Regulate the Microbiota of Women Than Men. 35681391 8 15 theme harmful 838:844 arg1 types 846:850 the harmful types 834:850 the harmful types 834:850 DOP can increase the relative abundance of benign microbiota and decrease the harmful types. 35681391 0 16 theme officinale 11:20 arg1 Polysaccharides 22:36 Dendrobium officinale Polysaccharides 0:36 Dendrobium officinale Polysaccharides 0:36 Dendrobium officinale Polysaccharides Better Regulate the Microbiota of Women Than Men. 35681391 10 17 theme men 1027:1029 arg1 microbiota 1008:1017 the microbiota 1004:1017 the microbiota of both men and women 1004:1039 Finally, the correlation analysis revealed that DOP was beneficial to the microbiota of both men and women. 35681391 1 18 theme Dendrobium 88:97 arg1 officinale 99:108 Dendrobium officinale 88:108 Dendrobium officinale 88:108 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 1 18 theme Dendrobium 88:97 arg1 supplement 137:146 a health supplement 128:146 a health supplement 128:146 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 8 19 theme microbiota 810:819 arg1 abundance 790:798 the relative abundance 777:798 the relative abundance of benign microbiota 777:819 DOP can increase the relative abundance of benign microbiota and decrease the harmful types. 35681391 3 20 theme 8000-12,000 355:365 arg1 bag 379:381 an 8000-12,000 Da dialysis bag 352:381 an 8000-12,000 Da dialysis bag 352:381 DOP was extracted and purified with an 8000-12,000 Da dialysis bag. 35681391 6 21 used used 555:558 arg2 sequencing 540:549 16S rDNA sequencing 531:549 16S rDNA sequencing 531:549 16S rDNA sequencing was used to analyze the diversity of human microbiota. 35681391 1 22 theme healthy 176:182 arg1 microbiota 188:197 healthy gut microbiota 176:197 healthy gut microbiota 176:197 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 9 23 theme DOP 919:921 arg1 treatment 923:931 DOP treatment 919:931 DOP treatment 919:931 Propionic acid content in women was significantly increased after DOP treatment. 35681391 1 24 theme different 249:257 arg1 genders 265:271 different human genders 249:271 different human genders 249:271 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 1 25 theme gut 184:186 arg1 microbiota 188:197 healthy gut microbiota 176:197 healthy gut microbiota 176:197 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 1 26 theme human 259:263 arg1 genders 265:271 different human genders 249:271 different human genders 249:271 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 1 27 from impact 239:244 arg1 genders 265:271 different human genders 249:271 different human genders 249:271 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 1 28 used used 120:123 arg2 officinale 99:108 Dendrobium officinale 88:108 Dendrobium officinale 88:108 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 1 28 used used 120:123 arg2 supplement 137:146 a health supplement 128:146 a health supplement 128:146 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 4 29 theme monosaccharide 409:422 arg1 composition 424:434 monosaccharide composition 409:434 monosaccharide composition 409:434 The molecular weight and monosaccharide composition were determined using HPGPC and GC. 35681391 7 30 contain contained 634:642 arg1 DOP 630:632 DOP 630:632 DOP 630:632 The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. 35681391 7 30 contain contained 634:642 arg2 fractions 648:656 two fractions 644:656 two fractions 644:656 The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. 35681391 3 31 theme Da 367:368 arg1 bag 379:381 an 8000-12,000 Da dialysis bag 352:381 an 8000-12,000 Da dialysis bag 352:381 DOP was extracted and purified with an 8000-12,000 Da dialysis bag. 35681391 9 32 theme Propionic 853:861 arg1 content 868:874 Propionic acid content 853:874 Propionic acid content in women 853:883 Propionic acid content in women was significantly increased after DOP treatment. 35681391 3 33 theme dialysis 370:377 arg1 bag 379:381 an 8000-12,000 Da dialysis bag 352:381 an 8000-12,000 Da dialysis bag 352:381 DOP was extracted and purified with an 8000-12,000 Da dialysis bag. 35681391 7 34 theme Da 712:713 arg1 weight 685:690 an average molecular weight 664:690 an average molecular weight of 277 kDa and 1318 Da 664:713 The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. 35681391 4 35 theme molecular 388:396 arg1 weight 398:403 The molecular weight 384:403 The molecular weight 384:403 The molecular weight and monosaccharide composition were determined using HPGPC and GC. 35681391 5 36 theme SCFA 525:528 arg1 content 514:520 the content 510:520 the content of SCFA 510:528 Gas chromatography was used to detect the content of SCFA. 35681391 9 37 from content 868:874 arg1 women 879:883 women 879:883 women 879:883 Propionic acid content in women was significantly increased after DOP treatment. 35681391 10 38 theme women 1035:1039 arg1 microbiota 1008:1017 the microbiota 1004:1017 the microbiota of both men and women 1004:1039 Finally, the correlation analysis revealed that DOP was beneficial to the microbiota of both men and women. 35681391 1 39 theme health 130:135 arg1 officinale 99:108 Dendrobium officinale 88:108 Dendrobium officinale 88:108 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 1 39 theme health 130:135 arg1 supplement 137:146 a health supplement 128:146 a health supplement 128:146 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 1 40 contain has 231:233 arg2 impact 239:244 its impact 235:244 its impact on different human genders 235:271 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 1 40 contain has 231:233 arg1 impact 166:171 its specific impact 153:171 its specific impact on healthy gut microbiota 153:197 Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. 35681391 5 41 used used 495:498 arg2 chromatography 476:489 Gas chromatography 472:489 Gas chromatography 472:489 Gas chromatography was used to detect the content of SCFA. 35681391 6 42 theme rDNA 535:538 arg1 sequencing 540:549 16S rDNA sequencing 531:549 16S rDNA sequencing 531:549 16S rDNA sequencing was used to analyze the diversity of human microbiota. 35681391 0 43 theme Women 72:76 arg1 Microbiota 58:67 the Microbiota 54:67 the Microbiota of Women Than Men 54:85 Dendrobium officinale Polysaccharides Better Regulate the Microbiota of Women Than Men. 35681391 6 44 theme microbiota 594:603 arg1 diversity 575:583 the diversity 571:583 the diversity of human microbiota 571:603 16S rDNA sequencing was used to analyze the diversity of human microbiota. 35681391 7 45 theme kDa 699:701 arg1 weight 685:690 an average molecular weight 664:690 an average molecular weight of 277 kDa and 1318 Da 664:713 The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. 36296078 0 0 theme In 86:87 arg1 Characterization 95:110 In Vitro Characterization 86:110 In Vitro Characterization 86:110 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 0 0 theme In 86:87 arg1 Scaffolds 3:11 3D Scaffolds 0:11 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 0:111 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 3 1 theme sodium 692:697 arg1 alginate 699:706 sodium alginate 692:706 sodium alginate 692:706 In this work, a method to fabricate 3D scaffolds by the assembly of bicomponent microgels made of sodium alginate and gelatin was proposed. 36296078 4 2 theme basic 848:852 arg1 properties 854:863 the basic properties 844:863 the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter) 844:1018 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 6 3 theme signals 1265:1271 arg1 effect 1243:1248 the effect 1239:1248 the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface 1239:1366 In vitro tests confirmed the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface. 36296078 4 4 theme needle 1003:1008 arg1 diameter 1010:1017 needle diameter 1003:1017 needle diameter 1003:1017 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 4 5 from properties 854:863 arg1 terms 885:889 terms 885:889 terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter) 885:1018 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 3 6 theme microgels 674:682 arg1 assembly 650:657 the assembly 646:657 the assembly of bicomponent microgels made of sodium alginate and gelatin 646:718 In this work, a method to fabricate 3D scaffolds by the assembly of bicomponent microgels made of sodium alginate and gelatin was proposed. 36296078 3 7 theme 3D 630:631 arg1 scaffolds 633:641 3D scaffolds 630:641 3D scaffolds 630:641 In this work, a method to fabricate 3D scaffolds by the assembly of bicomponent microgels made of sodium alginate and gelatin was proposed. 36296078 1 8 theme cell 250:253 arg1 response 255:262 in vitro cell response 241:262 in vitro cell response 241:262 In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. 36296078 4 9 theme image 810:814 arg1 analysis 816:823 image analysis 810:823 image analysis 810:823 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 2 10 theme electro 277:283 arg1 EFDA 312:315 EFDA 312:315 EFDA 312:315 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 2 10 theme electro 277:283 arg1 atomization 299:309 electro fluid dynamic atomization 277:309 electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies 277:373 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 4 11 theme process 938:944 arg1 parameters 946:955 process parameters 938:955 process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter) 938:1018 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 2 12 theme materials 535:543 arg1 features 509:516 the peculiar features 496:516 the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling) 496:591 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 6 13 dep In 1214:1215 arg1 vitro 1217:1221 vitro 1217:1221 vitro 1217:1221 In vitro tests confirmed the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface. 36296078 7 14 theme microgels 1414:1422 arg1 assemblies 1424:1433 alginate/gelatin microgels assemblies 1397:1433 alginate/gelatin microgels assemblies 1397:1433 Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. 36296078 4 15 with microscopy 779:788 arg1 support 799:805 the support 795:805 the support of image analysis 795:823 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 7 16 theme alginate/gelatin 1397:1412 arg1 assemblies 1424:1433 alginate/gelatin microgels assemblies 1397:1433 alginate/gelatin microgels assemblies 1397:1433 Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. 36296078 6 17 theme biological 1303:1312 arg1 response 1314:1321 the biological response 1299:1321 the biological response of hMSCs cultured onto the microgels surface 1299:1366 In vitro tests confirmed the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface. 36296078 2 18 theme hydrogel-like 521:533 arg1 materials 535:543 hydrogel-like materials 521:543 hydrogel-like materials (i.e., biocompatibility, wettability, swelling) 521:591 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 5 19 theme ninhydrin 1043:1051 arg1 essays 1053:1058 ninhydrin essays 1043:1058 ninhydrin essays 1043:1058 Chemical analysis via ninhydrin essays and FTIR analysis confirmed the presence of gelatin, mostly retained by physical interactions into the alginate network mediated by electrostatic forces. 36296078 2 20 dep biocompatibility 552:567 arg1 i.e. 546:549 i.e. 546:549 i.e. 546:549 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 4 21 dep voltage 964:970 arg1 i.e. 958:961 i.e. 958:961 i.e. 958:961 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 4 22 theme flow 973:976 arg1 rate 978:981 flow rate 973:981 flow rate 973:981 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 4 23 theme electrode 984:992 arg1 gap 994:996 electrode gap 984:996 electrode gap 984:996 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 7 24 dep in 1488:1489 arg1 vitro 1491:1495 vitro 1491:1495 vitro 1491:1495 Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. 36296078 6 25 theme microgels 1350:1358 arg1 surface 1360:1366 the microgels surface 1346:1366 the microgels surface 1346:1366 In vitro tests confirmed the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface. 36296078 0 26 dep In 86:87 arg1 Vitro 89:93 Vitro 89:93 Vitro 89:93 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 0 27 theme 3D 0:1 arg1 Characterization 95:110 In Vitro Characterization 86:110 In Vitro Characterization 86:110 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 0 27 theme 3D 0:1 arg1 Scaffolds 3:11 3D Scaffolds 0:11 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 0:111 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 0 27 theme 3D 0:1 arg1 Optimization 69:80 Process Optimization 61:80 Process Optimization 61:80 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 6 28 theme In 1214:1215 arg1 tests 1223:1227 In vitro tests 1214:1227 In vitro tests 1214:1227 In vitro tests confirmed the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface. 36296078 2 29 theme technologies 362:373 arg1 family 335:340 the family 331:340 the family of electro-assisted technologies 331:373 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 5 30 theme physical 1132:1139 arg1 interactions 1141:1152 physical interactions 1132:1152 physical interactions into the alginate network mediated by electrostatic forces 1132:1211 Chemical analysis via ninhydrin essays and FTIR analysis confirmed the presence of gelatin, mostly retained by physical interactions into the alginate network mediated by electrostatic forces. 36296078 4 31 theme correlation 894:904 arg1 terms 885:889 terms 885:889 terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter) 885:1018 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 2 32 theme dynamic 291:297 arg1 EFDA 312:315 EFDA 312:315 EFDA 312:315 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 2 32 theme dynamic 291:297 arg1 atomization 299:309 electro fluid dynamic atomization 277:309 electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies 277:373 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 2 33 theme proteins 425:432 arg1 dropping 390:397 the dropping 386:397 the dropping of polysaccharides and/or proteins solutions 386:442 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 7 34 theme friendly 1531:1538 arg1 microenvironment 1540:1555 a friendly microenvironment 1529:1555 a friendly microenvironment 1529:1555 Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. 36296078 2 35 theme electro-assisted 345:360 arg1 technologies 362:373 electro-assisted technologies 345:373 electro-assisted technologies 345:373 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 5 36 theme Chemical 1021:1028 arg1 analysis 1030:1037 Chemical analysis 1021:1037 Chemical analysis via ninhydrin essays 1021:1058 Chemical analysis via ninhydrin essays and FTIR analysis confirmed the presence of gelatin, mostly retained by physical interactions into the alginate network mediated by electrostatic forces. 36296078 2 37 theme fluid 285:289 arg1 EFDA 312:315 EFDA 312:315 EFDA 312:315 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 2 37 theme fluid 285:289 arg1 atomization 299:309 electro fluid dynamic atomization 277:309 electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies 277:373 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 2 38 theme polysaccharides 402:416 arg1 dropping 390:397 the dropping 386:397 the dropping of polysaccharides and/or proteins solutions 386:442 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 0 39 theme Microgels 41:49 arg1 Assembly 51:58 Bicomponent Microgels Assembly 29:58 Bicomponent Microgels Assembly 29:58 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 4 40 theme particle 914:921 arg1 morphology 923:932 particle morphology 914:932 particle morphology 914:932 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 1 41 dep in 241:242 arg1 vitro 244:248 vitro 244:248 vitro 244:248 In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. 36296078 6 42 theme biochemical 1253:1263 arg1 signals 1265:1271 biochemical signals 1253:1271 biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface 1253:1366 In vitro tests confirmed the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface. 36296078 7 43 theme in 1488:1489 arg1 functions 1503:1511 in vitro cells functions 1488:1511 in vitro cells functions 1488:1511 Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. 36296078 1 44 theme 3D 210:211 arg1 models 213:218 3D models 210:218 3D models suitable to evaluate in vitro cell response 210:262 In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. 36296078 0 45 theme Bicomponent 29:39 arg1 Assembly 51:58 Bicomponent Microgels Assembly 29:58 Bicomponent Microgels Assembly 29:58 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 5 46 theme gelatin 1104:1110 arg1 presence 1092:1099 the presence 1088:1099 the presence 1088:1099 Chemical analysis via ninhydrin essays and FTIR analysis confirmed the presence of gelatin, mostly retained by physical interactions into the alginate network mediated by electrostatic forces. 36296078 2 47 dep materials 535:543 arg1 biocompatibility 552:567 biocompatibility 552:567 biocompatibility 552:567 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 2 47 dep materials 535:543 arg1 swelling 583:590 swelling 583:590 swelling 583:590 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 2 47 dep materials 535:543 arg1 wettability 570:580 wettability 570:580 wettability 570:580 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 5 48 theme alginate 1163:1170 arg1 network 1172:1178 the alginate network 1159:1178 the alginate network mediated by electrostatic forces 1159:1211 Chemical analysis via ninhydrin essays and FTIR analysis confirmed the presence of gelatin, mostly retained by physical interactions into the alginate network mediated by electrostatic forces. 36296078 1 49 theme models 213:218 arg1 fabrication 195:205 the fabrication 191:205 the fabrication of 3D models suitable to evaluate in vitro cell response 191:262 In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. 36296078 7 50 theme in 1572:1573 arg1 interactions 1586:1597 in vitro cell interactions 1572:1597 in vitro cell interactions 1572:1597 Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. 36296078 7 51 theme cells 1497:1501 arg1 functions 1503:1511 in vitro cells functions 1488:1511 in vitro cells functions 1488:1511 Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. 36296078 4 52 theme blocks 875:880 arg1 properties 854:863 the basic properties 844:863 the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter) 844:1018 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 2 53 theme peculiar 500:507 arg1 features 509:516 the peculiar features 496:516 the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling) 496:591 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 3 54 dep method 610:615 arg1 fabricate 620:628 fabricate 620:628 to fabricate 3D scaffolds by the assembly of bicomponent microgels made of sodium alginate and gelatin 617:718 In this work, a method to fabricate 3D scaffolds by the assembly of bicomponent microgels made of sodium alginate and gelatin was proposed. 36296078 5 55 theme FTIR 1064:1067 arg1 analysis 1069:1076 FTIR analysis 1064:1076 FTIR analysis 1064:1076 Chemical analysis via ninhydrin essays and FTIR analysis confirmed the presence of gelatin, mostly retained by physical interactions into the alginate network mediated by electrostatic forces. 36296078 2 56 theme micro-scaled 455:466 arg1 hydrogels 468:476 micro-scaled hydrogels 455:476 micro-scaled hydrogels 455:476 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 4 57 theme analysis 816:823 arg1 support 799:805 the support 795:805 the support of image analysis 795:823 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 4 58 theme single 868:873 arg1 blocks 875:880 single blocks 868:880 single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter) 868:1018 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 4 59 from terms 885:889 arg1 properties 854:863 the basic properties 844:863 the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter) 844:1018 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 2 60 dep polysaccharides 402:416 arg1 solutions 434:442 solutions 434:442 solutions 434:442 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 1 61 theme last 120:123 arg1 decade 125:130 the last decade 116:130 the last decade 116:130 In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. 36296078 7 62 theme cell 1581:1584 arg1 interactions 1586:1597 in vitro cell interactions 1572:1597 in vitro cell interactions 1572:1597 Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. 36296078 3 63 theme bicomponent 662:672 arg1 microgels 674:682 bicomponent microgels 662:682 bicomponent microgels made of sodium alginate and gelatin 662:718 In this work, a method to fabricate 3D scaffolds by the assembly of bicomponent microgels made of sodium alginate and gelatin was proposed. 36296078 4 64 theme electron 770:777 arg1 microscopy 779:788 optical and scanning electron microscopy 749:788 microscopy 779:788 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 4 65 theme first 737:741 arg1 step 743:746 first step 737:746 first step 737:746 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 1 66 theme suitable 220:227 arg1 models 213:218 3D models 210:218 3D models suitable to evaluate in vitro cell response 210:262 In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. 36296078 4 67 theme optical 749:755 arg1 microscopy 779:788 optical and scanning electron microscopy 749:788 microscopy 779:788 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 4 68 from blocks 875:880 arg1 terms 885:889 terms 885:889 terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter) 885:1018 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 4 69 theme scanning 761:768 arg1 microscopy 779:788 optical and scanning electron microscopy 749:788 microscopy 779:788 As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). 36296078 2 70 with hydrogels 468:476 arg1 features 509:516 the peculiar features 496:516 the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling) 496:591 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 6 71 theme hMSCs 1326:1330 arg1 response 1314:1321 the biological response 1299:1321 the biological response of hMSCs cultured onto the microgels surface 1299:1366 In vitro tests confirmed the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface. 36296078 5 72 theme electrostatic 1192:1204 arg1 forces 1206:1211 electrostatic forces 1192:1211 electrostatic forces 1192:1211 Chemical analysis via ninhydrin essays and FTIR analysis confirmed the presence of gelatin, mostly retained by physical interactions into the alginate network mediated by electrostatic forces. 36296078 7 73 dep in 1572:1573 arg1 vitro 1575:1579 vitro 1575:1579 vitro 1575:1579 Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. 36296078 0 74 dep Scaffolds 3:11 arg1 Fabrication 13:23 Fabrication 13:23 Fabrication 13:23 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 0 74 dep Scaffolds 3:11 arg1 Characterization 95:110 In Vitro Characterization 86:110 In Vitro Characterization 86:110 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 0 74 dep Scaffolds 3:11 arg1 Optimization 69:80 Process Optimization 61:80 Process Optimization 61:80 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 0 74 dep Scaffolds 3:11 arg1 Scaffolds 3:11 3D Scaffolds 0:11 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 0:111 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 1 75 theme different 133:141 arg1 approaches 157:166 different technological approaches 133:166 different technological approaches 133:166 In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. 36296078 0 76 theme Process 61:67 arg1 Optimization 69:80 Process Optimization 61:80 Process Optimization 61:80 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 0 76 theme Process 61:67 arg1 Scaffolds 3:11 3D Scaffolds 0:11 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 0:111 3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization. 36296078 7 77 theme 3D 1459:1460 arg1 scaffolds 1462:1470 3D scaffolds 1459:1470 3D scaffolds 1459:1470 Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. 36296078 2 78 with microgels 481:489 arg1 features 509:516 the peculiar features 496:516 the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling) 496:591 Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). 36296078 1 79 theme technological 143:155 arg1 approaches 157:166 different technological approaches 133:166 different technological approaches 133:166 In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. 36296078 1 80 theme in 241:242 arg1 response 255:262 in vitro cell response 241:262 in vitro cell response 241:262 In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. 35605676 7 0 theme EngBF 1507:1511 arg1 variants 1513:1520 the EngBF variants 1503:1520 the EngBF variants 1503:1520 In addition, the kcat/KM of the EngBF variants for cleavage of the Neu5Acα2-3Galβ1-3GalNAc glycan increased between 5 and 70 times from pH 4.5 to pH 6.0. 35605676 1 1 gly glycopeptides 362:374 arg2 glycopeptides 362:374 glycopeptides 362:374 glycopeptides 362:374 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 5 2 theme O-linked 1225:1232 arg1 glycan 1234:1239 the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan 1197:1239 the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin 1197:1264 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 6 3 dep substitutions 1432:1444 arg1 E1294 M 1447:1453 E1294 M 1447:1453 E1294 M 1447:1453 Among the mutant EngBF variants listed above, only E1294A was shown to release Neu5Acα2-3Galβ1-3GalNAc from fetuin, which subsequently was also demonstrated for the substitutions: E1294 M, E1294H and E1294K. 35605676 6 3 dep substitutions 1432:1444 arg1 substitutions 1432:1444 the substitutions 1428:1444 the substitutions: E1294 M, E1294H and E1294K 1428:1472 Among the mutant EngBF variants listed above, only E1294A was shown to release Neu5Acα2-3Galβ1-3GalNAc from fetuin, which subsequently was also demonstrated for the substitutions: E1294 M, E1294H and E1294K. 35605676 6 3 dep substitutions 1432:1444 arg1 E1294K 1467:1472 E1294K 1467:1472 E1294K 1467:1472 Among the mutant EngBF variants listed above, only E1294A was shown to release Neu5Acα2-3Galβ1-3GalNAc from fetuin, which subsequently was also demonstrated for the substitutions: E1294 M, E1294H and E1294K. 35605676 6 3 dep substitutions 1432:1444 arg1 E1294H 1456:1461 E1294H 1456:1461 E1294H 1456:1461 Among the mutant EngBF variants listed above, only E1294A was shown to release Neu5Acα2-3Galβ1-3GalNAc from fetuin, which subsequently was also demonstrated for the substitutions: E1294 M, E1294H and E1294K. 35605676 7 4 theme variants 1513:1520 arg1 kcat/KM 1492:1498 the kcat/KM 1488:1498 the kcat/KM of the EngBF variants for cleavage of the Neu5Acα2-3Galβ1-3GalNAc glycan 1488:1571 In addition, the kcat/KM of the EngBF variants for cleavage of the Neu5Acα2-3Galβ1-3GalNAc glycan increased between 5 and 70 times from pH 4.5 to pH 6.0. 35605676 5 5 theme EngBF 1095:1099 arg1 D1295A 1143:1148 D1295A 1143:1148 D1295A 1143:1148 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 5 5 theme EngBF 1095:1099 arg1 E1294A 1132:1137 E1294A 1132:1137 E1294A 1132:1137 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 5 5 theme EngBF 1095:1099 arg1 variants 1101:1108 the mutant EngBF variants 1084:1108 the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A 1084:1148 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 5 5 theme EngBF 1095:1099 arg1 Q894A 1117:1121 Q894A 1117:1121 Q894A 1117:1121 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 1 6 dep serine 330:335 arg1 residues 350:357 residues 350:357 residues 350:357 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 5 7 theme present 1241:1247 arg1 glycan 1234:1239 the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan 1197:1239 the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin 1197:1264 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 3 8 from fluorophore 800:810 arg1 methylumbelliferyl 813:830 methylumbelliferyl 813:830 methylumbelliferyl 813:830 However, work published by others (ACS Chem Biol 2021, 16, 2004-2015) during the preparation of the present manuscript demonstrated that the enzymes from several bacteria are able to hydrolyze this glycan from the fluorophore, methylumbelliferyl. 35605676 3 8 from fluorophore 800:810 arg1 glycan 784:789 this glycan 779:789 this glycan from the fluorophore 779:810 However, work published by others (ACS Chem Biol 2021, 16, 2004-2015) during the preparation of the present manuscript demonstrated that the enzymes from several bacteria are able to hydrolyze this glycan from the fluorophore, methylumbelliferyl. 35605676 5 9 link O-linked 1225:1232 arg1 glycan 1234:1239 the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan 1197:1239 the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin 1197:1264 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 4 10 theme Neu5Acα2-3Galβ1-3GalNAc 1019:1041 arg1 accommodation 1002:1014 accommodation 1002:1014 accommodation of Neu5Acα2-3Galβ1-3GalNAc 1002:1041 Based on molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae, substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc were identified. 35605676 0 11 from reactivity 96:105 arg1 Fetuin 110:115 Fetuin 110:115 Fetuin 110:115 Engineering Bifidobacterium longum Endo-α-N-acetylgalactosaminidase for Neu5Acα2-3Galβ1-3GalNAc reactivity on Fetuin. 35605676 4 12 theme EngBF 870:874 arg1 homolog 876:882 the EngBF homolog 866:882 the EngBF homolog 866:882 Based on molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae, substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc were identified. 35605676 4 12 theme EngBF 870:874 arg1 EngSP 885:889 EngSP 885:889 EngSP 885:889 Based on molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae, substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc were identified. 35605676 2 13 theme wider 441:445 arg1 spectrum 457:464 a wider substrate spectrum 439:464 a wider substrate spectrum 439:464 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 2 14 theme mucin 547:551 arg1 glycan 553:558 the α2-3 sialidated mucin glycan 527:558 the α2-3 sialidated mucin glycan 527:558 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 2 14 theme mucin 547:551 arg1 Neu5Acα2-3Galβ1-3GalNAc 561:583 Neu5Acα2-3Galβ1-3GalNAc 561:583 Neu5Acα2-3Galβ1-3GalNAc 561:583 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 1 15 from threonine 340:348 arg1 -proteins 380:388 -proteins 380:388 -proteins 380:388 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 15 from threonine 340:348 arg1 glycopeptides 362:374 glycopeptides 362:374 glycopeptides 362:374 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 3 16 theme several 740:746 arg1 bacteria 748:755 several bacteria 740:755 several bacteria 740:755 However, work published by others (ACS Chem Biol 2021, 16, 2004-2015) during the preparation of the present manuscript demonstrated that the enzymes from several bacteria are able to hydrolyze this glycan from the fluorophore, methylumbelliferyl. 35605676 6 17 theme mutant 1277:1282 arg1 variants 1290:1297 the mutant EngBF variants 1273:1297 the mutant EngBF variants listed above 1273:1310 Among the mutant EngBF variants listed above, only E1294A was shown to release Neu5Acα2-3Galβ1-3GalNAc from fetuin, which subsequently was also demonstrated for the substitutions: E1294 M, E1294H and E1294K. 35605676 1 18 from serine 330:335 arg1 -proteins 380:388 -proteins 380:388 -proteins 380:388 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 18 from serine 330:335 arg1 glycopeptides 362:374 glycopeptides 362:374 glycopeptides 362:374 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 2 19 theme family 424:429 arg1 enzymes 403:409 other enzymes 397:409 other enzymes of the GH101 family 397:429 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 3 20 from bacteria 748:755 arg1 able 761:764 able 761:764 able 761:764 However, work published by others (ACS Chem Biol 2021, 16, 2004-2015) during the preparation of the present manuscript demonstrated that the enzymes from several bacteria are able to hydrolyze this glycan from the fluorophore, methylumbelliferyl. 35605676 3 20 from bacteria 748:755 arg1 enzymes 727:733 the enzymes 723:733 the enzymes from several bacteria 723:755 However, work published by others (ACS Chem Biol 2021, 16, 2004-2015) during the preparation of the present manuscript demonstrated that the enzymes from several bacteria are able to hydrolyze this glycan from the fluorophore, methylumbelliferyl. 35605676 4 21 theme amino 950:954 arg1 residues 961:968 active site amino acid residues 938:968 active site amino acid residues 938:968 Based on molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae, substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc were identified. 35605676 2 22 theme GH101 470:474 arg1 member 476:481 no GH101 member 467:481 no GH101 member 467:481 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 4 23 theme site 945:948 arg1 residues 961:968 active site amino acid residues 938:968 active site amino acid residues 938:968 Based on molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae, substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc were identified. 35605676 7 24 theme glycan 1566:1571 arg1 cleavage 1526:1533 cleavage 1526:1533 cleavage of the Neu5Acα2-3Galβ1-3GalNAc glycan 1526:1571 In addition, the kcat/KM of the EngBF variants for cleavage of the Neu5Acα2-3Galβ1-3GalNAc glycan increased between 5 and 70 times from pH 4.5 to pH 6.0. 35605676 4 25 with substitution 922:933 arg1 potential 979:987 the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc 975:1041 the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc 975:1041 Based on molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae, substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc were identified. 35605676 1 26 theme glycoside 202:210 arg1 family 222:227 the glycoside hydrolase family GH101 198:233 the glycoside hydrolase family GH101 198:233 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 0 27 theme Neu5Acα2-3Galβ1-3GalNAc 72:94 arg1 reactivity 96:105 Neu5Acα2-3Galβ1-3GalNAc reactivity 72:105 Neu5Acα2-3Galβ1-3GalNAc reactivity on Fetuin 72:115 Engineering Bifidobacterium longum Endo-α-N-acetylgalactosaminidase for Neu5Acα2-3Galβ1-3GalNAc reactivity on Fetuin. 35605676 5 28 theme Neu5Acα2-3Galβ1-3GalNAc 1201:1223 arg1 glycan 1234:1239 the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan 1197:1239 the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin 1197:1264 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 4 29 theme residues 961:968 arg1 substitution 922:933 substitution 922:933 substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc 922:1041 Based on molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae, substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc were identified. 35605676 5 30 theme bovine 1252:1257 arg1 fetuin 1259:1264 bovine fetuin 1252:1264 bovine fetuin 1252:1264 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 4 31 theme molecular 842:850 arg1 docking 852:858 molecular docking 842:858 molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae 842:919 Based on molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae, substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc were identified. 35605676 1 32 theme strict 245:250 arg1 preference 252:261 a strict preference 243:261 a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins 243:388 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 32 theme strict 245:250 arg1 O-linked 318:325 O-linked 318:325 O-linked 318:325 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 3 33 dep ACS 621:623 arg1 Biol 630:633 Biol 630:633 Biol 630:633 However, work published by others (ACS Chem Biol 2021, 16, 2004-2015) during the preparation of the present manuscript demonstrated that the enzymes from several bacteria are able to hydrolyze this glycan from the fluorophore, methylumbelliferyl. 35605676 4 34 theme acid 956:959 arg1 residues 961:968 active site amino acid residues 938:968 active site amino acid residues 938:968 Based on molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae, substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc were identified. 35605676 1 35 contain has 239:241 arg1 Endo-α-N-acetylgalactosaminidase 118:149 Endo-α-N-acetylgalactosaminidase 118:149 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) 118:185 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 35 contain has 239:241 arg2 O-linked 318:325 O-linked 318:325 O-linked 318:325 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 35 contain has 239:241 arg2 preference 252:261 a strict preference 243:261 a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins 243:388 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 36 theme mucin 275:279 arg1 Galβ1-3GalNAc 294:306 Galβ1-3GalNAc 294:306 Galβ1-3GalNAc 294:306 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 36 theme mucin 275:279 arg1 glycan 286:291 the mucin type glycan 271:291 the mucin type glycan 271:291 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 7 37 theme Neu5Acα2-3Galβ1-3GalNAc 1542:1564 arg1 glycan 1566:1571 the Neu5Acα2-3Galβ1-3GalNAc glycan 1538:1571 the Neu5Acα2-3Galβ1-3GalNAc glycan 1538:1571 In addition, the kcat/KM of the EngBF variants for cleavage of the Neu5Acα2-3Galβ1-3GalNAc glycan increased between 5 and 70 times from pH 4.5 to pH 6.0. 35605676 2 38 theme other 397:401 arg1 enzymes 403:409 other enzymes 397:409 other enzymes of the GH101 family 397:429 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 3 39 theme present 686:692 arg1 manuscript 694:703 the present manuscript 682:703 the present manuscript 682:703 However, work published by others (ACS Chem Biol 2021, 16, 2004-2015) during the preparation of the present manuscript demonstrated that the enzymes from several bacteria are able to hydrolyze this glycan from the fluorophore, methylumbelliferyl. 35605676 6 40 theme EngBF 1284:1288 arg1 variants 1290:1297 the mutant EngBF variants 1273:1297 the mutant EngBF variants listed above 1273:1310 Among the mutant EngBF variants listed above, only E1294A was shown to release Neu5Acα2-3Galβ1-3GalNAc from fetuin, which subsequently was also demonstrated for the substitutions: E1294 M, E1294H and E1294K. 35605676 4 41 theme active 938:943 arg1 residues 961:968 active site amino acid residues 938:968 active site amino acid residues 938:968 Based on molecular docking using the EngBF homolog, EngSP from Streptococcus pneumoniae, substitution of active site amino acid residues with the potential to allow for accommodation of Neu5Acα2-3Galβ1-3GalNAc were identified. 35605676 3 42 theme manuscript 694:703 arg1 preparation 667:677 the preparation 663:677 the preparation of the present manuscript 663:703 However, work published by others (ACS Chem Biol 2021, 16, 2004-2015) during the preparation of the present manuscript demonstrated that the enzymes from several bacteria are able to hydrolyze this glycan from the fluorophore, methylumbelliferyl. 35605676 1 43 theme type 281:284 arg1 Galβ1-3GalNAc 294:306 Galβ1-3GalNAc 294:306 Galβ1-3GalNAc 294:306 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 43 theme type 281:284 arg1 glycan 286:291 the mucin type glycan 271:291 the mucin type glycan 271:291 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 5 44 theme mutant 1088:1093 arg1 D1295A 1143:1148 D1295A 1143:1148 D1295A 1143:1148 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 5 44 theme mutant 1088:1093 arg1 E1294A 1132:1137 E1294A 1132:1137 E1294A 1132:1137 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 5 44 theme mutant 1088:1093 arg1 variants 1101:1108 the mutant EngBF variants 1084:1108 the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A 1084:1148 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 5 44 theme mutant 1088:1093 arg1 Q894A 1117:1121 Q894A 1117:1121 Q894A 1117:1121 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 2 45 theme sialidated 536:545 arg1 glycan 553:558 the α2-3 sialidated mucin glycan 527:558 the α2-3 sialidated mucin glycan 527:558 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 2 45 theme sialidated 536:545 arg1 Neu5Acα2-3Galβ1-3GalNAc 561:583 Neu5Acα2-3Galβ1-3GalNAc 561:583 Neu5Acα2-3Galβ1-3GalNAc 561:583 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 2 46 theme substrate 447:455 arg1 spectrum 457:464 a wider substrate spectrum 439:464 a wider substrate spectrum 439:464 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 1 47 attach O-linked 318:325 arg2 O-linked 318:325 O-linked 318:325 O-linked 318:325 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 47 attach O-linked 318:325 arg1 threonine 340:348 threonine 340:348 threonine 340:348 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 47 attach O-linked 318:325 arg2 preference 252:261 a strict preference 243:261 a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins 243:388 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 1 47 attach O-linked 318:325 arg1 serine 330:335 serine 330:335 serine 330:335 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 2 48 theme GH101 418:422 arg1 family 424:429 the GH101 family 414:429 the GH101 family 414:429 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 1 49 from longum 172:177 arg1 Endo-α-N-acetylgalactosaminidase 118:149 Endo-α-N-acetylgalactosaminidase 118:149 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) 118:185 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 35605676 5 50 dep variants 1101:1108 arg1 D1295A 1143:1148 D1295A 1143:1148 D1295A 1143:1148 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 5 50 dep variants 1101:1108 arg1 E1294A 1132:1137 E1294A 1132:1137 E1294A 1132:1137 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 5 50 dep variants 1101:1108 arg1 variants 1101:1108 the mutant EngBF variants 1084:1108 the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A 1084:1148 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 5 50 dep variants 1101:1108 arg1 Q894A 1117:1121 Q894A 1117:1121 Q894A 1117:1121 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 2 51 theme α2-3 531:534 arg1 glycan 553:558 the α2-3 sialidated mucin glycan 527:558 the α2-3 sialidated mucin glycan 527:558 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 2 51 theme α2-3 531:534 arg1 Neu5Acα2-3Galβ1-3GalNAc 561:583 Neu5Acα2-3Galβ1-3GalNAc 561:583 Neu5Acα2-3Galβ1-3GalNAc 561:583 While other enzymes of the GH101 family exhibit a wider substrate spectrum, no GH101 member has until recently been reported to process the α2-3 sialidated mucin glycan, Neu5Acα2-3Galβ1-3GalNAc. 35605676 5 52 attach present 1241:1247 arg1 fetuin 1259:1264 bovine fetuin 1252:1264 bovine fetuin 1252:1264 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 5 52 attach present 1241:1247 arg2 glycan 1234:1239 the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan 1197:1239 the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin 1197:1264 Based on this analysis, the mutant EngBF variants W750A, Q894A, K1199A, E1294A and D1295A were prepared and tested, for activity towards the Neu5Acα2-3Galβ1-3GalNAc O-linked glycan present on bovine fetuin. 35605676 1 53 theme hydrolase 212:220 arg1 family 222:227 the glycoside hydrolase family GH101 198:233 the glycoside hydrolase family GH101 198:233 Endo-α-N-acetylgalactosaminidase from Bifidobacterium longum (EngBF) belongs to the glycoside hydrolase family GH101 and has a strict preference towards the mucin type glycan, Galβ1-3GalNAc, which is O-linked to serine or threonine residues on glycopeptides and -proteins. 37179738 5 0 dep factors 933:939 arg1 TNF-α 1016:1020 TNF-α 1016:1020 TNF-α 1016:1020 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 0 dep factors 933:939 arg1 factor-α 1006:1013 interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α 942:1013 interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) 942:1021 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 6 1 theme receptors 1321:1329 arg1 γ 1331:1331 peroxisome proliferator-activated receptors γ 1287:1331 peroxisome proliferator-activated receptors γ (PPARγ) 1287:1339 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 1 theme receptors 1321:1329 arg1 PPARγ 1334:1338 PPARγ 1334:1338 PPARγ 1334:1338 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 2 theme A 1229:1229 arg1 HMGCR 1242:1246 HMGCR 1242:1246 HMGCR 1242:1246 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 2 theme A 1229:1229 arg1 reductase 1231:1239 3-hydroxy-3-methylglutaryl coenzyme A reductase 1193:1239 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) 1193:1247 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 3 3 theme blood 494:498 arg1 lipid 500:504 blood lipid 494:504 blood lipid 494:504 This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. 37179738 6 4 theme acid 1378:1381 arg1 synthetase 1383:1392 fatty acid synthetase 1372:1392 fatty acid synthetase (FAS) 1372:1398 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 4 theme acid 1378:1381 arg1 FAS 1395:1397 FAS 1395:1397 FAS 1395:1397 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 0 5 theme rodent 96:101 arg1 study 103:107 A rodent study 94:107 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 0:108 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 37179738 6 6 theme enzymes 1121:1127 arg1 expression 1103:1112 The expression 1099:1112 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), 1099:1460 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 7 theme coenzyme 1220:1227 arg1 HMGCR 1242:1246 HMGCR 1242:1246 HMGCR 1242:1246 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 7 theme coenzyme 1220:1227 arg1 reductase 1231:1239 3-hydroxy-3-methylglutaryl coenzyme A reductase 1193:1239 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) 1193:1247 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 7 8 theme flora 1685:1689 arg1 abundance 1657:1665 abundance 1657:1665 abundance 1657:1665 Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. 37179738 7 8 theme flora 1685:1689 arg1 composition 1641:1651 composition 1641:1651 composition 1641:1651 Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. 37179738 5 9 theme serum 914:918 arg1 factors 933:939 serum inflammatory factors 914:939 serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) 914:1022 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 6 10 theme fatty 1372:1376 arg1 synthetase 1383:1392 fatty acid synthetase 1372:1392 fatty acid synthetase (FAS) 1372:1398 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 10 theme fatty 1372:1376 arg1 FAS 1395:1397 FAS 1395:1397 FAS 1395:1397 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 8 11 theme theoretical 1748:1758 arg1 basis 1760:1764 a theoretical basis 1746:1764 a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia 1746:1877 This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia. 37179738 6 12 theme peroxisome 1287:1296 arg1 receptors 1321:1329 peroxisome proliferator-activated receptors 1287:1329 peroxisome proliferator-activated receptors γ (PPARγ) 1287:1339 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 5 13 theme inflammatory 920:931 arg1 factors 933:939 serum inflammatory factors 914:939 serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) 914:1022 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 4 14 from effect 719:724 arg1 regulation 746:755 lipid metabolism regulation 729:755 lipid metabolism regulation 729:755 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 3 15 theme hepatic 532:538 arg1 axes 555:558 hepatic and intestinal axes 532:558 hepatic and intestinal axes 532:558 This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. 37179738 5 16 theme molecule-1 890:899 arg1 downregulation 800:813 the downregulation 796:813 the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) 796:1022 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 7 17 theme intestinal 1608:1617 arg1 barrier 1619:1625 the intestinal barrier 1604:1625 the intestinal barrier 1604:1625 Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. 37179738 4 18 theme dose-dependent 667:680 arg1 effect 682:687 a dose-dependent effect 665:687 a dose-dependent effect on ADPN levels 665:702 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 5 19 theme cell 832:835 arg1 ICAM-1 858:863 ICAM-1 858:863 ICAM-1 858:863 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 19 theme cell 832:835 arg1 molecule-1 846:855 intercellular cell adhesion molecule-1 818:855 intercellular cell adhesion molecule-1 (ICAM-1) 818:864 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 3 20 theme intestinal 510:519 arg1 health 521:526 intestinal health 510:526 intestinal health 510:526 This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. 37179738 5 21 theme adhesion 837:844 arg1 ICAM-1 858:863 ICAM-1 858:863 ICAM-1 858:863 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 21 theme adhesion 837:844 arg1 molecule-1 846:855 intercellular cell adhesion molecule-1 818:855 intercellular cell adhesion molecule-1 (ICAM-1) 818:864 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 3 22 theme Tibetan 431:437 arg1 TTP 462:464 TTP 462:464 TTP 462:464 This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. 37179738 3 22 theme Tibetan 431:437 arg1 polysaccharide 446:459 Tibetan turnip polysaccharide 431:459 Tibetan turnip polysaccharide (TTP) 431:465 This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. 37179738 5 23 theme TTP 768:770 arg1 intervention 772:783 TTP intervention 768:783 TTP intervention 768:783 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 2 24 theme flora 383:387 arg1 growth 362:367 the growth 358:367 the growth of intestinal flora 358:387 Studies have shown that polysaccharides absorbed by the intestinal tract can regulate blood lipids and facilitate the growth of intestinal flora. 37179738 8 25 with patients 1850:1857 arg1 hyperlipidemia 1864:1877 hyperlipidemia 1864:1877 hyperlipidemia 1864:1877 This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia. 37179738 7 26 theme intestinal 1534:1543 arg1 tissues 1545:1551 intestinal tissues 1534:1551 intestinal tissues 1534:1551 Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. 37179738 8 27 theme rhythm 1793:1798 arg1 regulation 1774:1783 the regulation 1770:1783 the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia 1770:1877 This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia. 37179738 7 28 theme intestinal 1674:1683 arg1 flora 1685:1689 the intestinal flora 1670:1689 the intestinal flora 1670:1689 Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. 37179738 2 29 theme intestinal 372:381 arg1 flora 383:387 intestinal flora 372:387 intestinal flora 372:387 Studies have shown that polysaccharides absorbed by the intestinal tract can regulate blood lipids and facilitate the growth of intestinal flora. 37179738 0 30 theme Healthy 0:6 arg1 regulation 8:17 Healthy regulation 0:17 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 0:108 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 37179738 7 31 dep composition 1641:1651 arg1 the 1637:1639 the 1637:1639 the 1637:1639 Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. 37179738 8 32 theme body 1788:1791 arg1 rhythm 1793:1798 body rhythm 1788:1798 body rhythm 1788:1798 This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia. 37179738 5 33 theme intercellular 818:830 arg1 ICAM-1 858:863 ICAM-1 858:863 ICAM-1 858:863 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 33 theme intercellular 818:830 arg1 molecule-1 846:855 intercellular cell adhesion molecule-1 818:855 intercellular cell adhesion molecule-1 (ICAM-1) 818:864 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 2 34 theme intestinal 300:309 arg1 tract 311:315 the intestinal tract 296:315 the intestinal tract 296:315 Studies have shown that polysaccharides absorbed by the intestinal tract can regulate blood lipids and facilitate the growth of intestinal flora. 37179738 5 35 theme molecule-1 846:855 arg1 downregulation 800:813 the downregulation 796:813 the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) 796:1022 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 0 36 theme Tibetan 22:28 arg1 polysaccharides 47:61 Tibetan Brassica rapa L. polysaccharides 22:61 Tibetan Brassica rapa L. polysaccharides 22:61 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 37179738 6 37 theme key 1117:1119 arg1 enzymes 1121:1127 key enzymes 1117:1127 key enzymes associated with cholesterol and triglyceride synthesis 1117:1182 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 37 theme key 1117:1119 arg1 7α-hydroxylase 1262:1275 cholesterol 7α-hydroxylase 1250:1275 cholesterol 7α-hydroxylase (CYP7A1) 1250:1284 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 37 theme key 1117:1119 arg1 carboxylase 1353:1363 acetyl-CoA carboxylase 1342:1363 acetyl-CoA carboxylase (ACC) 1342:1369 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 37 theme key 1117:1119 arg1 synthetase 1383:1392 fatty acid synthetase 1372:1392 fatty acid synthetase (FAS) 1372:1398 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 37 theme key 1117:1119 arg1 γ 1331:1331 peroxisome proliferator-activated receptors γ 1287:1331 peroxisome proliferator-activated receptors γ (PPARγ) 1287:1339 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 37 theme key 1117:1119 arg1 proteins-1c 1438:1448 sterol-regulatory element binding proteins-1c 1404:1448 sterol-regulatory element binding proteins-1c (SREBP-1c) 1404:1459 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 37 theme key 1117:1119 arg1 reductase 1231:1239 3-hydroxy-3-methylglutaryl coenzyme A reductase 1193:1239 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) 1193:1247 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 8 38 theme functional 1803:1812 arg1 foods 1814:1818 functional foods 1803:1818 functional foods 1803:1818 This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia. 37179738 5 39 theme vascular 867:874 arg1 VCAM-1 902:907 VCAM-1 902:907 VCAM-1 902:907 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 39 theme vascular 867:874 arg1 molecule-1 890:899 vascular cell adhesion molecule-1 867:899 vascular cell adhesion molecule-1 (VCAM-1) 867:908 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 4 40 theme ADPN 692:695 arg1 levels 697:702 ADPN levels 692:702 ADPN levels 692:702 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 4 41 theme lipid 729:733 arg1 regulation 746:755 lipid metabolism regulation 729:755 lipid metabolism regulation 729:755 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 6 42 theme acetyl-CoA 1342:1351 arg1 ACC 1366:1368 ACC 1366:1368 ACC 1366:1368 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 42 theme acetyl-CoA 1342:1351 arg1 carboxylase 1353:1363 acetyl-CoA carboxylase 1342:1363 acetyl-CoA carboxylase (ACC) 1342:1369 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 3 43 theme intestinal 544:553 arg1 axes 555:558 hepatic and intestinal axes 532:558 hepatic and intestinal axes 532:558 This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. 37179738 6 44 theme binding 1430:1436 arg1 proteins-1c 1438:1448 sterol-regulatory element binding proteins-1c 1404:1448 sterol-regulatory element binding proteins-1c (SREBP-1c) 1404:1459 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 44 theme binding 1430:1436 arg1 SREBP-1c 1451:1458 SREBP-1c 1451:1458 SREBP-1c 1451:1458 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 4 45 theme fat 652:654 arg1 accumulation 630:641 the accumulation 626:641 the accumulation of liver fat 626:654 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 4 45 theme fat 652:654 arg1 size 603:606 the size 599:606 the size of adipocytes 599:620 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 0 46 theme rapa 39:42 arg1 polysaccharides 47:61 Tibetan Brassica rapa L. polysaccharides 22:61 Tibetan Brassica rapa L. polysaccharides 22:61 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 37179738 5 47 theme cell 876:879 arg1 VCAM-1 902:907 VCAM-1 902:907 VCAM-1 902:907 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 47 theme cell 876:879 arg1 molecule-1 890:899 vascular cell adhesion molecule-1 867:899 vascular cell adhesion molecule-1 (VCAM-1) 867:908 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 6 48 theme triglyceride 1161:1172 arg1 synthesis 1174:1182 triglyceride synthesis 1161:1182 triglyceride synthesis 1161:1182 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 49 theme element 1422:1428 arg1 proteins-1c 1438:1448 sterol-regulatory element binding proteins-1c 1404:1448 sterol-regulatory element binding proteins-1c (SREBP-1c) 1404:1459 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 49 theme element 1422:1428 arg1 SREBP-1c 1451:1458 SREBP-1c 1451:1458 SREBP-1c 1451:1458 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 4 50 theme adipocytes 611:620 arg1 accumulation 630:641 the accumulation 626:641 the accumulation of liver fat 626:654 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 4 50 theme adipocytes 611:620 arg1 size 603:606 the size 599:606 the size of adipocytes 599:620 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 0 51 theme Brassica 30:37 arg1 polysaccharides 47:61 Tibetan Brassica rapa L. polysaccharides 22:61 Tibetan Brassica rapa L. polysaccharides 22:61 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 37179738 5 52 from progression 1058:1068 arg1 body 1093:1096 the body 1089:1096 the body 1089:1096 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 53 theme interleukin-1β 964:977 arg1 TNF-α 1016:1020 TNF-α 1016:1020 TNF-α 1016:1020 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 53 theme interleukin-1β 964:977 arg1 factor-α 1006:1013 interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α 942:1013 interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) 942:1021 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 0 54 theme polysaccharides 47:61 arg1 regulation 8:17 Healthy regulation 0:17 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 0:108 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 37179738 5 55 theme inflammation 1073:1084 arg1 progression 1058:1068 the progression 1054:1068 the progression of inflammation in the body 1054:1096 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 6 56 theme proliferator-activated 1298:1319 arg1 receptors 1321:1329 peroxisome proliferator-activated receptors 1287:1329 peroxisome proliferator-activated receptors γ (PPARγ) 1287:1339 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 5 57 theme factors 933:939 arg1 downregulation 800:813 the downregulation 796:813 the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) 796:1022 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 3 58 theme protective 475:484 arg1 role 486:489 a protective role 473:489 a protective role 473:489 This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. 37179738 0 59 theme L. 44:45 arg1 polysaccharides 47:61 Tibetan Brassica rapa L. polysaccharides 22:61 Tibetan Brassica rapa L. polysaccharides 22:61 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 37179738 6 60 theme 3-hydroxy-3-methylglutaryl 1193:1218 arg1 HMGCR 1242:1246 HMGCR 1242:1246 HMGCR 1242:1246 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 60 theme 3-hydroxy-3-methylglutaryl 1193:1218 arg1 reductase 1231:1239 3-hydroxy-3-methylglutaryl coenzyme A reductase 1193:1239 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) 1193:1247 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 8 61 theme potential 1824:1832 arg1 intervention 1834:1845 potential intervention 1824:1845 potential intervention in patients with hyperlipidemia 1824:1877 This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia. 37179738 2 62 theme blood 330:334 arg1 lipids 336:341 blood lipids 330:341 blood lipids 330:341 Studies have shown that polysaccharides absorbed by the intestinal tract can regulate blood lipids and facilitate the growth of intestinal flora. 37179738 6 63 theme sterol-regulatory 1404:1420 arg1 proteins-1c 1438:1448 sterol-regulatory element binding proteins-1c 1404:1448 sterol-regulatory element binding proteins-1c (SREBP-1c) 1404:1459 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 63 theme sterol-regulatory 1404:1420 arg1 SREBP-1c 1451:1458 SREBP-1c 1451:1458 SREBP-1c 1451:1458 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 5 64 theme interleukin-6 942:954 arg1 TNF-α 1016:1020 TNF-α 1016:1020 TNF-α 1016:1020 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 64 theme interleukin-6 942:954 arg1 factor-α 1006:1013 interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α 942:1013 interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) 942:1021 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 65 theme adhesion 881:888 arg1 VCAM-1 902:907 VCAM-1 902:907 VCAM-1 902:907 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 65 theme adhesion 881:888 arg1 molecule-1 890:899 vascular cell adhesion molecule-1 867:899 vascular cell adhesion molecule-1 (VCAM-1) 867:908 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 4 66 from effect 682:687 arg1 levels 697:702 ADPN levels 692:702 ADPN levels 692:702 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 6 67 theme cholesterol 1250:1260 arg1 7α-hydroxylase 1262:1275 cholesterol 7α-hydroxylase 1250:1275 cholesterol 7α-hydroxylase (CYP7A1) 1250:1284 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 6 67 theme cholesterol 1250:1260 arg1 CYP7A1 1278:1283 CYP7A1 1278:1283 CYP7A1 1278:1283 The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. 37179738 5 68 theme tumor 991:995 arg1 necrosis 997:1004 tumor necrosis 991:1004 tumor necrosis 991:1004 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 4 69 theme metabolism 735:744 arg1 regulation 746:755 lipid metabolism regulation 729:755 lipid metabolism regulation 729:755 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 7 70 theme SCFAs 1719:1723 arg1 levels 1709:1714 the levels 1705:1714 the levels of SCFAs 1705:1723 Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. 37179738 1 71 theme common 130:135 arg1 disorder 147:154 a common metabolic disorder 128:154 a common metabolic disorder 128:154 Hyperlipidemia is a common metabolic disorder, which can lead to obesity, hypertension, diabetes, atherosclerosis and other diseases. 37179738 1 71 theme common 130:135 arg1 Hyperlipidemia 110:123 Hyperlipidemia 110:123 Hyperlipidemia 110:123 Hyperlipidemia is a common metabolic disorder, which can lead to obesity, hypertension, diabetes, atherosclerosis and other diseases. 37179738 8 72 from foods 1814:1818 arg1 patients 1850:1857 patients 1850:1857 patients with hyperlipidemia 1850:1877 This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia. 37179738 5 73 theme necrosis 997:1004 arg1 TNF-α 1016:1020 TNF-α 1016:1020 TNF-α 1016:1020 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 5 73 theme necrosis 997:1004 arg1 factor-α 1006:1013 interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α 942:1013 interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) 942:1021 Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. 37179738 0 74 dep regulation 8:17 arg1 study 103:107 A rodent study 94:107 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 0:108 Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study. 37179738 7 75 theme high-fat 1563:1570 arg1 diet 1572:1575 high-fat diet 1563:1575 high-fat diet 1563:1575 Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. 37179738 1 76 theme metabolic 137:145 arg1 disorder 147:154 a common metabolic disorder 128:154 a common metabolic disorder 128:154 Hyperlipidemia is a common metabolic disorder, which can lead to obesity, hypertension, diabetes, atherosclerosis and other diseases. 37179738 1 76 theme metabolic 137:145 arg1 Hyperlipidemia 110:123 Hyperlipidemia 110:123 Hyperlipidemia 110:123 Hyperlipidemia is a common metabolic disorder, which can lead to obesity, hypertension, diabetes, atherosclerosis and other diseases. 37179738 3 77 theme turnip 439:444 arg1 TTP 462:464 TTP 462:464 TTP 462:464 This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. 37179738 3 77 theme turnip 439:444 arg1 polysaccharide 446:459 Tibetan turnip polysaccharide 431:459 Tibetan turnip polysaccharide (TTP) 431:465 This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. 37179738 8 78 from intervention 1834:1845 arg1 patients 1850:1857 patients 1850:1857 patients with hyperlipidemia 1850:1877 This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia. 37179738 4 79 theme liver 646:650 arg1 fat 652:654 liver fat 646:654 liver fat 646:654 Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. 37179738 7 80 theme barrier 1619:1625 arg1 integrity 1591:1599 the integrity 1587:1599 the integrity of the intestinal barrier 1587:1625 Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. 37179738 1 81 theme other 228:232 arg1 diseases 234:241 other diseases 228:241 other diseases 228:241 Hyperlipidemia is a common metabolic disorder, which can lead to obesity, hypertension, diabetes, atherosclerosis and other diseases. 35901886 7 0 theme components 1365:1374 arg1 result 1394:1399 the combined result 1381:1399 the combined result of dissolution and hydrolysis reaction 1381:1438 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 7 0 theme components 1365:1374 arg1 concentrations 1331:1344 the concentrations 1327:1344 the concentrations of soluble organic components 1327:1374 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 11 1 theme higher 1978:1983 arg1 % 1976:1976 9.8 % 1972:1976 9.8 % higher than SS and SS-HTT 1972:2002 The highest methane production was 298.1 mL CH4/g VSadd for DS hydrothermally treated at 170 °C, which were 125 % and 9.8 % higher than SS and SS-HTT, respectively. 35901886 1 2 theme secondary 320:328 arg1 SS 338:339 SS 338:339 SS 338:339 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 2 theme secondary 320:328 arg1 sludge 330:335 secondary sludge 320:335 secondary sludge (SS) 320:340 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 3 3 theme organic 583:589 arg1 solubilization 598:611 The organic matter solubilization 579:611 The organic matter solubilization during HTT 579:622 The organic matter solubilization during HTT showed no obvious difference for two sludge, but for the different organic components. 35901886 6 4 theme sludge 1146:1151 arg1 EPS 1153:1155 sludge EPS 1146:1155 sludge EPS 1146:1155 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 7 5 theme soluble 1349:1355 arg1 components 1365:1374 soluble organic components 1349:1374 soluble organic components 1349:1374 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 2 6 theme °C 529:530 arg1 °C 539:540 120 °C to 170 °C 525:540 120 °C to 170 °C 525:540 The results showed that organic matter solubilization increased significantly at 120 °C to 170 °C, then decreased at 200 °C to 250 °C. 35901886 6 7 theme polymeric 1037:1045 arg1 EPS 1059:1061 EPS 1059:1061 EPS 1059:1061 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 6 7 theme polymeric 1037:1045 arg1 substances 1047:1056 extracellular polymeric substances 1023:1056 residual extracellular polymeric substances (EPS) content 1014:1070 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 10 8 theme enhanced 1829:1836 arg1 dewaterability 1838:1851 enhanced dewaterability 1829:1851 enhanced dewaterability 1829:1851 The EPS structure damage also contributed to the high percentage of free moisture, resulting in enhanced dewaterability. 35901886 4 9 from temperature 831:841 arg1 rate 819:822 the higher dissolution rate 796:822 the higher dissolution rate at low temperature 796:841 The polysaccharides are easier to be dissolved than protein, which was manifested by the higher dissolution rate at low temperature. 35901886 6 10 theme residual 1014:1021 arg1 content 1064:1070 residual extracellular polymeric substances (EPS) content 1014:1070 residual extracellular polymeric substances (EPS) content 1014:1070 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 6 11 theme DNA 1112:1114 arg1 concentrations 1116:1129 DNA concentrations 1112:1129 DNA concentrations 1112:1129 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 11 12 theme CH4/g 1898:1902 arg1 VSadd 1904:1908 298.1 mL CH4/g VSadd 1889:1908 298.1 mL CH4/g VSadd 1889:1908 The highest methane production was 298.1 mL CH4/g VSadd for DS hydrothermally treated at 170 °C, which were 125 % and 9.8 % higher than SS and SS-HTT, respectively. 35901886 11 12 theme CH4/g 1898:1902 arg1 production 1874:1883 The highest methane production 1854:1883 The highest methane production 1854:1883 The highest methane production was 298.1 mL CH4/g VSadd for DS hydrothermally treated at 170 °C, which were 125 % and 9.8 % higher than SS and SS-HTT, respectively. 35901886 1 13 theme treatment 171:179 arg1 changes 309:315 structure changes 299:315 structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion 299:423 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 13 theme treatment 171:179 arg1 effects 147:153 The effects 143:153 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization 143:293 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 6 14 theme N-acetylglucosamine 1088:1106 arg1 decrease 1002:1009 The decrease 998:1009 The decrease of residual extracellular polymeric substances (EPS) content 998:1070 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 6 14 theme N-acetylglucosamine 1088:1106 arg1 increase 1076:1083 increase 1076:1083 increase of N-acetylglucosamine and DNA concentrations 1076:1129 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 1 15 theme downstream 379:388 arg1 dewatering 390:399 downstream dewatering 379:399 downstream dewatering 379:399 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 2 16 theme matter 476:481 arg1 solubilization 483:496 organic matter solubilization 468:496 organic matter solubilization 468:496 The results showed that organic matter solubilization increased significantly at 120 °C to 170 °C, then decreased at 200 °C to 250 °C. 35901886 0 17 theme raw 118:120 arg1 Effects 0:6 Effects 0:6 Effects of hydrothermal treatment on organic compositions 0:56 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 0 17 theme raw 118:120 arg1 dewatering 82:91 dewatering 82:91 dewatering 82:91 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 0 17 theme raw 118:120 arg1 production 104:113 biogas production 97:113 biogas production 97:113 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 1 18 theme sludge 330:335 arg1 changes 309:315 structure changes 299:315 structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion 299:423 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 18 theme sludge 330:335 arg1 effects 147:153 The effects 143:153 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization 143:293 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 4 19 theme low 827:829 arg1 temperature 831:841 low temperature 827:841 low temperature 827:841 The polysaccharides are easier to be dissolved than protein, which was manifested by the higher dissolution rate at low temperature. 35901886 0 20 theme digested 126:133 arg1 sludge 135:140 digested sludge 126:140 digested sludge 126:140 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 11 21 theme highest 1858:1864 arg1 VSadd 1904:1908 298.1 mL CH4/g VSadd 1889:1908 298.1 mL CH4/g VSadd 1889:1908 The highest methane production was 298.1 mL CH4/g VSadd for DS hydrothermally treated at 170 °C, which were 125 % and 9.8 % higher than SS and SS-HTT, respectively. 35901886 11 21 theme highest 1858:1864 arg1 production 1874:1883 The highest methane production 1854:1883 The highest methane production 1854:1883 The highest methane production was 298.1 mL CH4/g VSadd for DS hydrothermally treated at 170 °C, which were 125 % and 9.8 % higher than SS and SS-HTT, respectively. 35901886 1 22 dep time 220:223 arg1 min 257:259 10 min to 60 min 244:259 10 min to 60 min 244:259 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 22 dep time 220:223 arg1 °C 240:241 120 °C to 250 °C 226:241 120 °C to 250 °C 226:241 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 8 23 dep balance 1552:1558 arg1 transformation 1581:1594 transformation 1581:1594 transformation 1581:1594 The hydrolysis and polymerization reaction were intensified at 170 °C to 250 °C, which was verified by the COD balance and molecular weight transformation. 35901886 6 24 theme wall 1166:1169 arg1 structure 1171:1179 cell wall structure 1161:1179 cell wall structure 1161:1179 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 2 25 dep °C 575:576 arg1 to 568:569 to 568:569 to 568:569 The results showed that organic matter solubilization increased significantly at 120 °C to 170 °C, then decreased at 200 °C to 250 °C. 35901886 4 26 theme higher 800:805 arg1 rate 819:822 the higher dissolution rate 796:822 the higher dissolution rate at low temperature 796:841 The polysaccharides are easier to be dissolved than protein, which was manifested by the higher dissolution rate at low temperature. 35901886 1 27 dep °C 240:241 arg1 to 233:234 to 233:234 to 233:234 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 28 theme sludge 355:360 arg1 changes 309:315 structure changes 299:315 structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion 299:423 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 28 theme sludge 355:360 arg1 effects 147:153 The effects 143:153 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization 143:293 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 7 29 theme molecular 1287:1295 arg1 distribution 1304:1315 molecular weight distribution 1287:1315 molecular weight distribution 1287:1315 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 8 30 dep °C 1518:1519 arg1 to 1511:1512 to 1511:1512 to 1511:1512 The hydrolysis and polymerization reaction were intensified at 170 °C to 250 °C, which was verified by the COD balance and molecular weight transformation. 35901886 3 31 theme different 681:689 arg1 components 699:708 the different organic components 677:708 the different organic components 677:708 The organic matter solubilization during HTT showed no obvious difference for two sludge, but for the different organic components. 35901886 6 32 theme high 1230:1233 arg1 solubilization 1250:1263 the high organic matter solubilization 1226:1263 the high organic matter solubilization 1226:1263 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 5 33 theme oxygen 976:981 arg1 demand 983:988 soluble chemical oxygen demand 959:988 soluble chemical oxygen demand (SCOD) 959:995 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 33 theme oxygen 976:981 arg1 SCOD 991:994 SCOD 991:994 SCOD 991:994 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 1 34 from changes 309:315 arg1 solubilization 280:293 organic matter solubilization 265:293 organic matter solubilization 265:293 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 12 35 theme AD 2125:2126 arg1 configurations 2128:2141 different HTT and AD configurations 2107:2141 configurations 2128:2141 This study provided an insight into the general mechanism of HTT and the application of different HTT and AD configurations. 35901886 1 36 from effects 147:153 arg1 solubilization 280:293 organic matter solubilization 265:293 organic matter solubilization 265:293 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 0 37 from Effects 0:6 arg1 compositions 45:56 organic compositions 37:56 organic compositions 37:56 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 2 38 theme °C 565:566 arg1 °C 575:576 200 °C to 250 °C 561:576 200 °C to 250 °C 561:576 The results showed that organic matter solubilization increased significantly at 120 °C to 170 °C, then decreased at 200 °C to 250 °C. 35901886 1 39 theme structure 299:307 arg1 changes 309:315 structure changes 299:315 structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion 299:423 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 6 40 theme extracellular 1023:1035 arg1 EPS 1059:1061 EPS 1059:1061 EPS 1059:1061 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 6 40 theme extracellular 1023:1035 arg1 substances 1047:1056 extracellular polymeric substances 1023:1056 residual extracellular polymeric substances (EPS) content 1014:1070 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 5 41 theme soluble 959:965 arg1 demand 983:988 soluble chemical oxygen demand 959:988 soluble chemical oxygen demand (SCOD) 959:995 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 41 theme soluble 959:965 arg1 SCOD 991:994 SCOD 991:994 SCOD 991:994 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 42 theme soluble 869:875 arg1 component 877:885 the main soluble component 860:885 the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD) 860:995 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 42 theme soluble 869:875 arg1 protein 848:854 The protein 844:854 The protein 844:854 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 1 43 dep min 257:259 arg1 to 251:252 to 251:252 to 251:252 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 12 44 theme general 2059:2065 arg1 mechanism 2067:2075 the general mechanism 2055:2075 the general mechanism of HTT 2055:2082 This study provided an insight into the general mechanism of HTT and the application of different HTT and AD configurations. 35901886 0 45 theme hydrothermal 11:22 arg1 treatment 24:32 hydrothermal treatment 11:32 hydrothermal treatment 11:32 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 1 46 theme min 247:249 arg1 min 257:259 10 min to 60 min 244:259 10 min to 60 min 244:259 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 46 theme min 247:249 arg1 °C 240:241 120 °C to 250 °C 226:241 120 °C to 250 °C 226:241 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 9 47 theme hydrothermal 1707:1718 arg1 temperature 1720:1730 hydrothermal temperature 1707:1730 hydrothermal temperature 1707:1730 The hydrothermal time could further facilitate the organics dissolution and hydrolysis based on the effect of hydrothermal temperature. 35901886 0 48 theme structural 59:68 arg1 Effects 0:6 Effects 0:6 Effects of hydrothermal treatment on organic compositions 0:56 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 0 48 theme structural 59:68 arg1 properties 70:79 structural properties 59:79 structural properties 59:79 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 1 49 theme anaerobic 405:413 arg1 digestion 415:423 anaerobic digestion 405:423 anaerobic digestion 405:423 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 6 50 theme matter 1243:1248 arg1 solubilization 1250:1263 the high organic matter solubilization 1226:1263 the high organic matter solubilization 1226:1263 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 1 51 theme organic 265:271 arg1 solubilization 280:293 organic matter solubilization 265:293 organic matter solubilization 265:293 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 7 52 theme combined 1385:1392 arg1 concentrations 1331:1344 the concentrations 1327:1344 the concentrations of soluble organic components 1327:1374 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 7 52 theme combined 1385:1392 arg1 result 1394:1399 the combined result 1381:1399 the combined result of dissolution and hydrolysis reaction 1381:1438 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 7 53 theme organic 1357:1363 arg1 components 1365:1374 soluble organic components 1349:1374 soluble organic components 1349:1374 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 10 54 theme free 1801:1804 arg1 moisture 1806:1813 free moisture 1801:1813 free moisture 1801:1813 The EPS structure damage also contributed to the high percentage of free moisture, resulting in enhanced dewaterability. 35901886 1 55 theme °C 230:231 arg1 min 257:259 10 min to 60 min 244:259 10 min to 60 min 244:259 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 55 theme °C 230:231 arg1 °C 240:241 120 °C to 250 °C 226:241 120 °C to 250 °C 226:241 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 5 56 theme demand 983:988 arg1 demand 983:988 soluble chemical oxygen demand 959:988 soluble chemical oxygen demand (SCOD) 959:995 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 56 theme demand 983:988 arg1 % 954:954 44 % to 64 % 943:954 44 % to 64 % of soluble chemical oxygen demand (SCOD) 943:995 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 56 theme demand 983:988 arg1 SCOD 991:994 SCOD 991:994 SCOD 991:994 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 10 57 theme EPS 1737:1739 arg1 damage 1751:1756 The EPS structure damage 1733:1756 The EPS structure damage 1733:1756 The EPS structure damage also contributed to the high percentage of free moisture, resulting in enhanced dewaterability. 35901886 3 58 theme matter 591:596 arg1 solubilization 598:611 The organic matter solubilization 579:611 The organic matter solubilization during HTT 579:622 The organic matter solubilization during HTT showed no obvious difference for two sludge, but for the different organic components. 35901886 7 59 theme weight 1297:1302 arg1 distribution 1304:1315 molecular weight distribution 1287:1315 molecular weight distribution 1287:1315 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 3 60 theme obvious 634:640 arg1 difference 642:651 no obvious difference 631:651 no obvious difference for two sludge, but for the different organic components 631:708 The organic matter solubilization during HTT showed no obvious difference for two sludge, but for the different organic components. 35901886 6 61 theme concentrations 1116:1129 arg1 decrease 1002:1009 The decrease 998:1009 The decrease of residual extracellular polymeric substances (EPS) content 998:1070 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 6 61 theme concentrations 1116:1129 arg1 increase 1076:1083 increase 1076:1083 increase of N-acetylglucosamine and DNA concentrations 1076:1129 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 11 62 theme mL 1895:1896 arg1 VSadd 1904:1908 298.1 mL CH4/g VSadd 1889:1908 298.1 mL CH4/g VSadd 1889:1908 The highest methane production was 298.1 mL CH4/g VSadd for DS hydrothermally treated at 170 °C, which were 125 % and 9.8 % higher than SS and SS-HTT, respectively. 35901886 11 62 theme mL 1895:1896 arg1 production 1874:1883 The highest methane production 1854:1883 The highest methane production 1854:1883 The highest methane production was 298.1 mL CH4/g VSadd for DS hydrothermally treated at 170 °C, which were 125 % and 9.8 % higher than SS and SS-HTT, respectively. 35901886 8 63 theme molecular 1564:1572 arg1 weight 1574:1579 molecular weight 1564:1579 molecular weight 1564:1579 The hydrolysis and polymerization reaction were intensified at 170 °C to 250 °C, which was verified by the COD balance and molecular weight transformation. 35901886 1 64 theme hydrothermal 158:169 arg1 HTT 182:184 HTT 182:184 HTT 182:184 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 64 theme hydrothermal 158:169 arg1 treatment 171:179 hydrothermal treatment 158:179 hydrothermal treatment (HTT) under different temperatures 158:214 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 9 65 theme organics 1648:1655 arg1 dissolution 1657:1667 the organics dissolution 1644:1667 the organics dissolution 1644:1667 The hydrothermal time could further facilitate the organics dissolution and hydrolysis based on the effect of hydrothermal temperature. 35901886 2 66 dep °C 539:540 arg1 to 532:533 to 532:533 to 532:533 The results showed that organic matter solubilization increased significantly at 120 °C to 170 °C, then decreased at 200 °C to 250 °C. 35901886 7 67 theme Nitrogen 1266:1273 arg1 balance 1275:1281 Nitrogen balance 1266:1281 Nitrogen balance 1266:1281 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 1 68 theme dewatering 390:399 arg1 changes 309:315 structure changes 299:315 structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion 299:423 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 68 theme dewatering 390:399 arg1 effects 147:153 The effects 143:153 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization 143:293 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 2 69 theme organic 468:474 arg1 solubilization 483:496 organic matter solubilization 468:496 organic matter solubilization 468:496 The results showed that organic matter solubilization increased significantly at 120 °C to 170 °C, then decreased at 200 °C to 250 °C. 35901886 0 70 theme sludge 135:140 arg1 Effects 0:6 Effects 0:6 Effects of hydrothermal treatment on organic compositions 0:56 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 0 70 theme sludge 135:140 arg1 dewatering 82:91 dewatering 82:91 dewatering 82:91 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 0 70 theme sludge 135:140 arg1 production 104:113 biogas production 97:113 biogas production 97:113 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 5 71 theme % 946:946 arg1 demand 983:988 soluble chemical oxygen demand 959:988 soluble chemical oxygen demand (SCOD) 959:995 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 71 theme % 946:946 arg1 % 954:954 44 % to 64 % 943:954 44 % to 64 % of soluble chemical oxygen demand (SCOD) 943:995 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 71 theme % 946:946 arg1 SCOD 991:994 SCOD 991:994 SCOD 991:994 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 1 72 theme different 193:201 arg1 temperatures 203:214 different temperatures 193:214 different temperatures 193:214 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 9 73 theme hydrothermal 1601:1612 arg1 time 1614:1617 The hydrothermal time 1597:1617 The hydrothermal time 1597:1617 The hydrothermal time could further facilitate the organics dissolution and hydrolysis based on the effect of hydrothermal temperature. 35901886 6 74 theme content 1064:1070 arg1 decrease 1002:1009 The decrease 998:1009 The decrease of residual extracellular polymeric substances (EPS) content 998:1070 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 6 74 theme content 1064:1070 arg1 increase 1076:1083 increase 1076:1083 increase of N-acetylglucosamine and DNA concentrations 1076:1129 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 6 75 theme cell 1161:1164 arg1 structure 1171:1179 cell wall structure 1161:1179 cell wall structure 1161:1179 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 1 76 theme digested 346:353 arg1 DS 363:364 DS 363:364 DS 363:364 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 76 theme digested 346:353 arg1 sludge 355:360 digested sludge 346:360 digested sludge (DS) 346:365 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 6 77 theme organic 1235:1241 arg1 solubilization 1250:1263 the high organic matter solubilization 1226:1263 the high organic matter solubilization 1226:1263 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 11 78 theme methane 1866:1872 arg1 VSadd 1904:1908 298.1 mL CH4/g VSadd 1889:1908 298.1 mL CH4/g VSadd 1889:1908 The highest methane production was 298.1 mL CH4/g VSadd for DS hydrothermally treated at 170 °C, which were 125 % and 9.8 % higher than SS and SS-HTT, respectively. 35901886 11 78 theme methane 1866:1872 arg1 production 1874:1883 The highest methane production 1854:1883 The highest methane production 1854:1883 The highest methane production was 298.1 mL CH4/g VSadd for DS hydrothermally treated at 170 °C, which were 125 % and 9.8 % higher than SS and SS-HTT, respectively. 35901886 12 79 theme configurations 2128:2141 arg1 insight 2042:2048 an insight 2039:2048 an insight into the general mechanism of HTT 2039:2082 This study provided an insight into the general mechanism of HTT and the application of different HTT and AD configurations. 35901886 12 79 theme configurations 2128:2141 arg1 application 2092:2102 the application 2088:2102 the application of different HTT and AD configurations 2088:2141 This study provided an insight into the general mechanism of HTT and the application of different HTT and AD configurations. 35901886 6 80 theme substances 1047:1056 arg1 content 1064:1070 residual extracellular polymeric substances (EPS) content 1014:1070 residual extracellular polymeric substances (EPS) content 1014:1070 The decrease of residual extracellular polymeric substances (EPS) content and increase of N-acetylglucosamine and DNA concentrations indicated that sludge EPS and cell wall structure were damaged at 170 °C, which contributed to the high organic matter solubilization. 35901886 3 81 theme organic 691:697 arg1 components 699:708 the different organic components 677:708 the different organic components 677:708 The organic matter solubilization during HTT showed no obvious difference for two sludge, but for the different organic components. 35901886 1 82 theme matter 273:278 arg1 solubilization 280:293 organic matter solubilization 265:293 organic matter solubilization 265:293 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 4 83 theme dissolution 807:817 arg1 rate 819:822 the higher dissolution rate 796:822 the higher dissolution rate at low temperature 796:841 The polysaccharides are easier to be dissolved than protein, which was manifested by the higher dissolution rate at low temperature. 35901886 0 84 theme biogas 97:102 arg1 Effects 0:6 Effects 0:6 Effects of hydrothermal treatment on organic compositions 0:56 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 0 84 theme biogas 97:102 arg1 production 104:113 biogas production 97:113 biogas production 97:113 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 7 85 theme reaction 1431:1438 arg1 concentrations 1331:1344 the concentrations 1327:1344 the concentrations of soluble organic components 1327:1374 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 7 85 theme reaction 1431:1438 arg1 result 1394:1399 the combined result 1381:1399 the combined result of dissolution and hydrolysis reaction 1381:1438 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 12 86 theme different 2107:2115 arg1 HTT 2117:2119 different HTT and AD configurations 2107:2141 HTT 2117:2119 This study provided an insight into the general mechanism of HTT and the application of different HTT and AD configurations. 35901886 12 87 theme HTT 2080:2082 arg1 mechanism 2067:2075 the general mechanism 2055:2075 the general mechanism of HTT 2055:2082 This study provided an insight into the general mechanism of HTT and the application of different HTT and AD configurations. 35901886 5 88 theme main 864:867 arg1 component 877:885 the main soluble component 860:885 the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD) 860:995 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 88 theme main 864:867 arg1 protein 848:854 The protein 844:854 The protein 844:854 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 89 theme chemical 967:974 arg1 demand 983:988 soluble chemical oxygen demand 959:988 soluble chemical oxygen demand (SCOD) 959:995 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 5 89 theme chemical 967:974 arg1 SCOD 991:994 SCOD 991:994 SCOD 991:994 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 12 90 theme HTT 2117:2119 arg1 insight 2042:2048 an insight 2039:2048 an insight into the general mechanism of HTT 2039:2082 This study provided an insight into the general mechanism of HTT and the application of different HTT and AD configurations. 35901886 12 90 theme HTT 2117:2119 arg1 application 2092:2102 the application 2088:2102 the application of different HTT and AD configurations 2088:2141 This study provided an insight into the general mechanism of HTT and the application of different HTT and AD configurations. 35901886 0 91 theme treatment 24:32 arg1 Effects 0:6 Effects 0:6 Effects of hydrothermal treatment on organic compositions 0:56 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 0 91 theme treatment 24:32 arg1 dewatering 82:91 dewatering 82:91 dewatering 82:91 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 0 91 theme treatment 24:32 arg1 production 104:113 biogas production 97:113 biogas production 97:113 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 0 91 theme treatment 24:32 arg1 properties 70:79 structural properties 59:79 structural properties 59:79 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 8 92 theme hydrolysis 1445:1454 arg1 reaction 1475:1482 The hydrolysis and polymerization reaction 1441:1482 reaction 1475:1482 The hydrolysis and polymerization reaction were intensified at 170 °C to 250 °C, which was verified by the COD balance and molecular weight transformation. 35901886 0 93 theme organic 37:43 arg1 compositions 45:56 organic compositions 37:56 organic compositions 37:56 Effects of hydrothermal treatment on organic compositions, structural properties, dewatering and biogas production of raw and digested sludge. 35901886 7 94 theme hydrolysis 1420:1429 arg1 reaction 1431:1438 hydrolysis reaction 1420:1438 hydrolysis reaction 1420:1438 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 9 95 theme temperature 1720:1730 arg1 effect 1697:1702 the effect 1693:1702 the effect of hydrothermal temperature 1693:1730 The hydrothermal time could further facilitate the organics dissolution and hydrolysis based on the effect of hydrothermal temperature. 35901886 8 96 theme polymerization 1460:1473 arg1 reaction 1475:1482 The hydrolysis and polymerization reaction 1441:1482 reaction 1475:1482 The hydrolysis and polymerization reaction were intensified at 170 °C to 250 °C, which was verified by the COD balance and molecular weight transformation. 35901886 10 97 theme structure 1741:1749 arg1 damage 1751:1756 The EPS structure damage 1733:1756 The EPS structure damage 1733:1756 The EPS structure damage also contributed to the high percentage of free moisture, resulting in enhanced dewaterability. 35901886 7 98 theme dissolution 1404:1414 arg1 concentrations 1331:1344 the concentrations 1327:1344 the concentrations of soluble organic components 1327:1374 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 7 98 theme dissolution 1404:1414 arg1 result 1394:1399 the combined result 1381:1399 the combined result of dissolution and hydrolysis reaction 1381:1438 Nitrogen balance and molecular weight distribution indicated the concentrations of soluble organic components were the combined result of dissolution and hydrolysis reaction. 35901886 5 99 dep % 954:954 arg1 to 948:949 to 948:949 to 948:949 The protein was the main soluble component for both of hydrothermal SS and DS, which accounted for 44 % to 64 % of soluble chemical oxygen demand (SCOD). 35901886 10 100 theme high 1782:1785 arg1 percentage 1787:1796 the high percentage 1778:1796 the high percentage of free moisture 1778:1813 The EPS structure damage also contributed to the high percentage of free moisture, resulting in enhanced dewaterability. 35901886 1 101 theme digestion 415:423 arg1 changes 309:315 structure changes 299:315 structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion 299:423 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 101 theme digestion 415:423 arg1 effects 147:153 The effects 143:153 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization 143:293 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 11 102 theme 298.1 1889:1893 arg1 mL 1895:1896 mL 1895:1896 mL 1895:1896 The highest methane production was 298.1 mL CH4/g VSadd for DS hydrothermally treated at 170 °C, which were 125 % and 9.8 % higher than SS and SS-HTT, respectively. 35901886 1 103 theme time 220:223 arg1 changes 309:315 structure changes 299:315 structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion 299:423 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 1 103 theme time 220:223 arg1 effects 147:153 The effects 143:153 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization 143:293 The effects of hydrothermal treatment (HTT) under different temperatures and time (120 °C to 250 °C, 10 min to 60 min) on organic matter solubilization and structure changes of secondary sludge (SS) and digested sludge (DS), as well as downstream dewatering and anaerobic digestion were investigated. 35901886 2 104 dep increased 498:506 arg1 decreased 548:556 decreased 548:556 decreased at 200 °C to 250 °C 548:576 The results showed that organic matter solubilization increased significantly at 120 °C to 170 °C, then decreased at 200 °C to 250 °C. 35901886 8 105 theme °C 1508:1509 arg1 °C 1518:1519 170 °C to 250 °C 1504:1519 170 °C to 250 °C 1504:1519 The hydrolysis and polymerization reaction were intensified at 170 °C to 250 °C, which was verified by the COD balance and molecular weight transformation. 35901886 10 106 theme moisture 1806:1813 arg1 percentage 1787:1796 the high percentage 1778:1796 the high percentage of free moisture 1778:1813 The EPS structure damage also contributed to the high percentage of free moisture, resulting in enhanced dewaterability. 35901886 8 107 theme COD 1548:1550 arg1 balance 1552:1558 the COD balance 1544:1558 the COD balance 1544:1558 The hydrolysis and polymerization reaction were intensified at 170 °C to 250 °C, which was verified by the COD balance and molecular weight transformation. 36255678 4 0 from early 592:596 arg1 development 601:611 development 601:611 development 601:611 Brain is one of the tissues where O-GlcNAc is the most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development. 36255678 4 1 theme O-GlcNAc 568:575 arg1 deletion 547:554 deletion 547:554 deletion of neuronal O-GlcNAc 547:575 Brain is one of the tissues where O-GlcNAc is the most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development. 36255678 6 2 theme several 873:879 arg1 obesity 901:907 obesity 901:907 obesity 901:907 Conversely, too much or too little O-GlcNAc in the brain contributes to several disorders including obesity, intellectual disability and Alzheimer's disease. 36255678 6 2 theme several 873:879 arg1 disorders 881:889 several disorders 873:889 several disorders including obesity, intellectual disability and Alzheimer's disease 873:956 Conversely, too much or too little O-GlcNAc in the brain contributes to several disorders including obesity, intellectual disability and Alzheimer's disease. 36255678 1 3 theme threonine 160:168 arg1 serine 149:154 serine 149:154 serine 149:154 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 1 3 theme threonine 160:168 arg1 group 140:144 the hydroxyl group 127:144 the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins 127:204 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 1 3 theme threonine 160:168 arg1 threonine 160:168 threonine 160:168 threonine 160:168 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 4 4 theme neuronal 559:566 arg1 O-GlcNAc 568:575 neuronal O-GlcNAc 559:575 neuronal O-GlcNAc 559:575 Brain is one of the tissues where O-GlcNAc is the most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development. 36255678 3 5 theme gene 348:351 arg1 transcription 353:365 gene transcription 348:365 gene transcription 348:365 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. 36255678 5 6 theme normal 645:650 arg1 function 664:671 normal adult brain function 645:671 normal adult brain function 645:671 O-GlcNAc is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by O-GlcNAc. 36255678 5 7 theme adult 652:656 arg1 function 664:671 normal adult brain function 645:671 normal adult brain function 645:671 O-GlcNAc is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by O-GlcNAc. 36255678 5 8 from processes 688:696 arg1 part 735:738 part 735:738 part 735:738 O-GlcNAc is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by O-GlcNAc. 36255678 7 9 dep expression 992:1001 arg1 the 988:990 the 988:990 the 988:990 In this chapter, we describe the expression and regulation of O-GlcNAc in the nervous system. 36255678 1 10 theme nuclear 173:179 arg1 proteins 197:204 nuclear and cytoplasmic proteins 173:204 nuclear and cytoplasmic proteins 173:204 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 5 11 theme proteins 779:786 arg1 modification 754:765 the modification 750:765 the modification of specific proteins by O-GlcNAc 750:798 O-GlcNAc is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by O-GlcNAc. 36255678 1 12 from group 140:144 arg1 proteins 197:204 nuclear and cytoplasmic proteins 173:204 nuclear and cytoplasmic proteins 173:204 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 0 13 theme Brain 0:4 arg1 O-GlcNAcylation 6:20 Brain O-GlcNAcylation 0:20 Brain O-GlcNAcylation 0:20 Brain O-GlcNAcylation: From Molecular Mechanisms to Clinical Phenotype. 36255678 1 14 theme cytoplasmic 185:195 arg1 proteins 197:204 nuclear and cytoplasmic proteins 173:204 nuclear and cytoplasmic proteins 173:204 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 6 15 from O-GlcNAc 836:843 arg1 brain 852:856 the brain 848:856 the brain 848:856 Conversely, too much or too little O-GlcNAc in the brain contributes to several disorders including obesity, intellectual disability and Alzheimer's disease. 36255678 5 16 theme dynamic 680:686 arg1 processes 688:696 dynamic processes 680:696 dynamic processes like learning and memory at least in part 680:738 O-GlcNAc is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by O-GlcNAc. 36255678 3 17 theme protein 368:374 arg1 translation 376:386 protein translation 368:386 protein translation 368:386 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. 36255678 7 18 theme nervous 1037:1043 arg1 system 1045:1050 the nervous system 1033:1050 the nervous system 1033:1050 In this chapter, we describe the expression and regulation of O-GlcNAc in the nervous system. 36255678 3 19 contain contain 453:459 arg2 O-GlcNAc 461:468 O-GlcNAc 461:468 O-GlcNAc 461:468 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. 36255678 3 19 contain contain 453:459 arg1 Thousands 314:322 Thousands 314:322 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction 314:451 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. 36255678 3 19 contain contain 453:459 arg1 regulation 419:428 the regulation 415:428 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction 314:451 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. 36255678 1 20 theme β-N-acetylglucosamine 102:122 arg1 O-GlcNAc 72:79 O-GlcNAc 72:79 O-GlcNAc 72:79 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 1 20 theme β-N-acetylglucosamine 102:122 arg1 attachment 88:97 the attachment 84:97 the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins 84:204 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 7 21 theme O-GlcNAc 1021:1028 arg1 regulation 1007:1016 regulation 1007:1016 regulation 1007:1016 In this chapter, we describe the expression and regulation of O-GlcNAc in the nervous system. 36255678 7 21 theme O-GlcNAc 1021:1028 arg1 expression 992:1001 expression 992:1001 expression 992:1001 In this chapter, we describe the expression and regulation of O-GlcNAc in the nervous system. 36255678 6 22 theme little 829:834 arg1 O-GlcNAc 836:843 too much or too little O-GlcNAc 813:843 too much or too little O-GlcNAc in the brain 813:856 Conversely, too much or too little O-GlcNAc in the brain contributes to several disorders including obesity, intellectual disability and Alzheimer's disease. 36255678 3 23 theme transduction 440:451 arg1 Thousands 314:322 Thousands 314:322 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction 314:451 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. 36255678 3 23 theme transduction 440:451 arg1 regulation 419:428 the regulation 415:428 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction 314:451 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. 36255678 0 24 theme Molecular 28:36 arg1 Mechanisms 38:47 Molecular Mechanisms 28:47 Molecular Mechanisms 28:47 Brain O-GlcNAcylation: From Molecular Mechanisms to Clinical Phenotype. 36255678 1 25 attach attachment 88:97 arg2 β-N-acetylglucosamine 102:122 β-N-acetylglucosamine 102:122 β-N-acetylglucosamine 102:122 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 1 25 attach attachment 88:97 arg1 serine 149:154 serine 149:154 serine 149:154 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 1 25 attach attachment 88:97 arg1 group 140:144 the hydroxyl group 127:144 the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins 127:204 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 1 25 attach attachment 88:97 arg1 threonine 160:168 threonine 160:168 threonine 160:168 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 0 26 theme Clinical 52:59 arg1 Phenotype 61:69 Clinical Phenotype 52:69 Clinical Phenotype 52:69 Brain O-GlcNAcylation: From Molecular Mechanisms to Clinical Phenotype. 36255678 6 27 theme intellectual 910:921 arg1 disability 923:932 intellectual disability 910:932 intellectual disability 910:932 Conversely, too much or too little O-GlcNAc in the brain contributes to several disorders including obesity, intellectual disability and Alzheimer's disease. 36255678 5 28 theme brain 658:662 arg1 function 664:671 normal adult brain function 645:671 normal adult brain function 645:671 O-GlcNAc is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by O-GlcNAc. 36255678 0 29 dep Mechanisms 38:47 arg1 O-GlcNAcylation 6:20 Brain O-GlcNAcylation 0:20 Brain O-GlcNAcylation 0:20 Brain O-GlcNAcylation: From Molecular Mechanisms to Clinical Phenotype. 36255678 5 30 theme specific 770:777 arg1 proteins 779:786 specific proteins 770:786 specific proteins 770:786 O-GlcNAc is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by O-GlcNAc. 36255678 6 31 theme much 817:820 arg1 O-GlcNAc 836:843 too much or too little O-GlcNAc 813:843 too much or too little O-GlcNAc in the brain 813:856 Conversely, too much or too little O-GlcNAc in the brain contributes to several disorders including obesity, intellectual disability and Alzheimer's disease. 36255678 1 32 theme hydroxyl 131:138 arg1 serine 149:154 serine 149:154 serine 149:154 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 1 32 theme hydroxyl 131:138 arg1 group 140:144 the hydroxyl group 127:144 the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins 127:204 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 1 32 theme hydroxyl 131:138 arg1 threonine 160:168 threonine 160:168 threonine 160:168 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 4 33 theme early 592:596 arg1 death 586:590 death 586:590 death early in development 586:611 Brain is one of the tissues where O-GlcNAc is the most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development. 36255678 7 34 from expression 992:1001 arg1 system 1045:1050 the nervous system 1033:1050 the nervous system 1033:1050 In this chapter, we describe the expression and regulation of O-GlcNAc in the nervous system. 36255678 4 35 from development 601:611 arg1 early 592:596 early 592:596 early 592:596 Brain is one of the tissues where O-GlcNAc is the most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development. 36255678 3 36 theme signal 433:438 arg1 transduction 440:451 signal transduction 433:451 signal transduction 433:451 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. 36255678 7 37 from regulation 1007:1016 arg1 system 1045:1050 the nervous system 1033:1050 the nervous system 1033:1050 In this chapter, we describe the expression and regulation of O-GlcNAc in the nervous system. 36255678 3 38 theme proteins 327:334 arg1 Thousands 314:322 Thousands 314:322 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction 314:451 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. 36255678 3 38 theme proteins 327:334 arg1 regulation 419:428 the regulation 415:428 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction 314:451 Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. 36255678 4 39 theme tissues 491:497 arg1 one 480:482 one 480:482 one 480:482 Brain is one of the tissues where O-GlcNAc is the most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development. 36255678 4 39 theme tissues 491:497 arg1 tissues 491:497 the tissues 487:497 the tissues where O-GlcNAc is the most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development 487:611 Brain is one of the tissues where O-GlcNAc is the most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development. 36255678 1 40 theme serine 149:154 arg1 serine 149:154 serine 149:154 serine 149:154 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 1 40 theme serine 149:154 arg1 group 140:144 the hydroxyl group 127:144 the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins 127:204 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 36255678 1 40 theme serine 149:154 arg1 threonine 160:168 threonine 160:168 threonine 160:168 O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. 37050276 2 0 theme energy-dispersive 439:455 arg1 EDS 477:479 EDS 477:479 EDS 477:479 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 0 theme energy-dispersive 439:455 arg1 spectroscopy 463:474 energy-dispersive X-ray spectroscopy 439:474 energy-dispersive X-ray spectroscopy (EDS) 439:480 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 1 1 attach isolated 100:107 arg2 polysaccharide 81:94 A polysaccharide 79:94 A polysaccharide 79:94 A polysaccharide was isolated from the exudate of a buriti tree trunk (Mauritia flexuosa). 37050276 1 1 attach isolated 100:107 arg1 exudate 118:124 the exudate 114:124 the exudate of a buriti tree trunk (Mauritia flexuosa) 114:167 A polysaccharide was isolated from the exudate of a buriti tree trunk (Mauritia flexuosa). 37050276 4 2 with °C 926:927 arg1 loss 942:945 a mass loss 935:945 a mass loss of 56.33% 935:955 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 4 3 theme % 955:955 arg1 loss 942:945 a mass loss 935:945 a mass loss of 56.33% 935:955 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 1 4 theme buriti 131:136 arg1 flexuosa 159:166 a buriti tree trunk (Mauritia flexuosa) 129:167 a buriti tree trunk (Mauritia flexuosa) 129:167 A polysaccharide was isolated from the exudate of a buriti tree trunk (Mauritia flexuosa). 37050276 5 5 theme BG 1025:1026 arg1 process 1040:1046 the BG degradation process 1021:1046 the BG degradation process 1021:1046 In the temperature range of 255-290 °C, the energy involved in the BG degradation process was approximately 17 J/g. 37050276 3 6 theme Gal 729:731 arg1 conformers 741:750 Gal and Xyl conformers 729:750 Gal and Xyl conformers 729:750 In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. 37050276 3 7 dep studies 660:666 arg1 addition 625:632 addition 625:632 addition 625:632 In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. 37050276 4 8 theme tree 760:763 arg1 gum 765:767 Buriti tree gum 753:767 Buriti tree gum (BG) 753:772 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 4 8 theme tree 760:763 arg1 arabinogalactan 780:794 an arabinogalactan 777:794 an arabinogalactan 777:794 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 4 8 theme tree 760:763 arg1 BG 770:771 BG 770:771 BG 770:771 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 1 9 theme tree 138:141 arg1 flexuosa 159:166 a buriti tree trunk (Mauritia flexuosa) 129:167 a buriti tree trunk (Mauritia flexuosa) 129:167 A polysaccharide was isolated from the exudate of a buriti tree trunk (Mauritia flexuosa). 37050276 5 10 theme degradation 1028:1038 arg1 process 1040:1046 the BG degradation process 1021:1046 the BG degradation process 1021:1046 In the temperature range of 255-290 °C, the energy involved in the BG degradation process was approximately 17 J/g. 37050276 2 11 dep such 334:337 arg1 nuclear 390:396 nuclear 390:396 nuclear 390:396 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 5 12 theme °C 994:995 arg1 range 977:981 the temperature range 961:981 the temperature range of 255-290 °C 961:995 In the temperature range of 255-290 °C, the energy involved in the BG degradation process was approximately 17 J/g. 37050276 3 13 theme NMR 637:639 arg1 studies 660:666 NMR molecular modeling studies 637:666 NMR molecular modeling studies 637:666 In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. 37050276 2 14 theme elemental 245:253 arg1 composition 255:265 elemental composition 245:265 elemental composition 245:265 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 6 15 contain had 1144:1146 arg1 BG 1134:1135 BG 1134:1135 BG 1134:1135 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 6 15 contain had 1144:1146 arg2 morphology 1179:1188 an irregular and heterogeneous morphology 1148:1188 an irregular and heterogeneous morphology 1148:1188 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 2 16 theme such 334:337 arg1 resonance 407:415 such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance 334:415 such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C) 334:432 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 7 17 from presence 1329:1336 arg1 composition 1445:1455 the BG composition 1438:1455 the BG composition 1438:1455 EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition. 37050276 6 18 theme °C 1127:1128 arg1 temperature 1107:1117 a glass transition temperature 1088:1117 a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard 1088:1309 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 3 19 theme molecular 641:649 arg1 studies 660:666 NMR molecular modeling studies 637:666 NMR molecular modeling studies 637:666 In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. 37050276 1 20 theme trunk 143:147 arg1 flexuosa 159:166 a buriti tree trunk (Mauritia flexuosa) 129:167 a buriti tree trunk (Mauritia flexuosa) 129:167 A polysaccharide was isolated from the exudate of a buriti tree trunk (Mauritia flexuosa). 37050276 6 21 theme irregular 1151:1159 arg1 morphology 1179:1188 an irregular and heterogeneous morphology 1148:1188 an irregular and heterogeneous morphology 1148:1188 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 2 22 theme electron 566:573 arg1 SEM 587:589 SEM 587:589 SEM 587:589 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 22 theme electron 566:573 arg1 microscopy 575:584 scanning electron microscopy 557:584 scanning electron microscopy (SEM) 557:590 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 5 23 theme temperature 965:975 arg1 range 977:981 the temperature range 961:981 the temperature range of 255-290 °C 961:995 In the temperature range of 255-290 °C, the energy involved in the BG degradation process was approximately 17 J/g. 37050276 0 24 theme Structural 0:9 arg1 Characteristics 23:37 Structural and Thermal Characteristics 0:37 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 0:77 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 37050276 2 25 theme scanning 557:564 arg1 SEM 587:589 SEM 587:589 SEM 587:589 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 25 theme scanning 557:564 arg1 microscopy 575:584 scanning electron microscopy 557:584 scanning electron microscopy (SEM) 557:590 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 5 26 from J/g 1069:1071 arg1 range 977:981 the temperature range 961:981 the temperature range of 255-290 °C 961:995 In the temperature range of 255-290 °C, the energy involved in the BG degradation process was approximately 17 J/g. 37050276 4 27 theme mass 937:940 arg1 loss 942:945 a mass loss 935:945 a mass loss of 56.33% 935:955 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 1 28 theme Mauritia 150:157 arg1 flexuosa 159:166 a buriti tree trunk (Mauritia flexuosa) 129:167 a buriti tree trunk (Mauritia flexuosa) 129:167 A polysaccharide was isolated from the exudate of a buriti tree trunk (Mauritia flexuosa). 37050276 2 29 theme NMR 418:420 arg1 1H 422:423 NMR 1H 418:423 NMR 1H 418:423 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 7 30 theme calcium 1371:1377 arg1 presence 1329:1336 the presence 1325:1336 the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition 1325:1455 EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition. 37050276 7 31 theme BG 1442:1443 arg1 composition 1445:1455 the BG composition 1438:1455 the BG composition 1438:1455 EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition. 37050276 2 32 theme X-ray 597:601 arg1 XRD 616:618 XRD 616:618 XRD 616:618 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 32 theme X-ray 597:601 arg1 diffraction 603:613 X-ray diffraction 597:613 X-ray diffraction (XRD) 597:619 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 33 theme product 274:280 arg1 morphology 214:223 morphology 214:223 morphology 214:223 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 33 theme product 274:280 arg1 structure 184:192 The molecular structure 170:192 The molecular structure 170:192 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 33 theme product 274:280 arg1 composition 255:265 elemental composition 245:265 elemental composition 245:265 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 33 theme product 274:280 arg1 stability 203:211 thermal stability 195:211 thermal stability 195:211 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 33 theme product 274:280 arg1 crystallinity 226:238 crystallinity 226:238 crystallinity 226:238 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 1 34 theme flexuosa 159:166 arg1 exudate 118:124 the exudate 114:124 the exudate of a buriti tree trunk (Mauritia flexuosa) 114:167 A polysaccharide was isolated from the exudate of a buriti tree trunk (Mauritia flexuosa). 37050276 4 35 dep degrades 836:843 arg1 % 868:868 98.5% 864:868 98.5% 864:868 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 2 36 theme magnetic 398:405 arg1 resonance 407:415 such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance 334:415 such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C) 334:432 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 0 37 theme Thermal 15:21 arg1 Characteristics 23:37 Structural and Thermal Characteristics 0:37 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 0:77 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 37050276 3 38 theme modeling 651:658 arg1 studies 660:666 NMR molecular modeling studies 637:666 NMR molecular modeling studies 637:666 In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. 37050276 3 39 dep 1H 699:700 arg1 shifts 719:724 chemical shifts 710:724 chemical shifts 710:724 In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. 37050276 3 39 dep 1H 699:700 arg1 the 695:697 the 695:697 the 695:697 In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. 37050276 4 40 contain containing 797:806 arg2 Rha 808:810 Rha 808:810 Rha 808:810 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 4 40 contain containing 797:806 arg2 Ara 813:815 Ara 813:815 Ara 813:815 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 4 40 contain containing 797:806 arg2 Xyl 818:820 Xyl 818:820 Xyl 818:820 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 4 40 contain containing 797:806 arg2 Gal 827:829 Gal 827:829 Gal 827:829 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 4 40 contain containing 797:806 arg1 arabinogalactan 780:794 an arabinogalactan 777:794 an arabinogalactan 777:794 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 4 40 contain containing 797:806 arg1 gum 765:767 Buriti tree gum 753:767 Buriti tree gum (BG) 753:772 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 6 41 theme BG 1269:1270 arg1 nature 1259:1264 the amorphous nature 1245:1264 the amorphous nature of BG that was confirmed by the XRD standard 1245:1309 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 4 42 from °C 926:927 arg1 peak 911:914 a maximum degradation peak 889:914 a maximum degradation peak at 291.97 °C, with a mass loss of 56.33% 889:955 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 0 43 theme Buriti 42:47 arg1 flexuosa 68:75 Mauritia flexuosa 59:75 Mauritia flexuosa 59:75 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 37050276 0 43 theme Buriti 42:47 arg1 Gum 54:56 Buriti Tree Gum 42:56 Buriti Tree Gum (Mauritia flexuosa) 42:76 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 37050276 6 44 theme transition 1096:1105 arg1 temperature 1107:1117 a glass transition temperature 1088:1117 a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard 1088:1309 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 6 45 theme scaly 1216:1220 arg1 regions 1222:1228 scaly regions 1216:1228 scaly regions 1216:1228 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 2 46 theme infrared 360:367 arg1 FTIR 383:386 FTIR 383:386 FTIR 383:386 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 46 theme infrared 360:367 arg1 spectroscopy 369:380 Fourier-transform infrared spectroscopy 342:380 Fourier-transform infrared spectroscopy (FTIR) 342:387 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 6 47 theme heterogeneous 1165:1177 arg1 morphology 1179:1188 an irregular and heterogeneous morphology 1148:1188 an irregular and heterogeneous morphology 1148:1188 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 2 48 theme thermogravimetric 483:499 arg1 TG 511:512 TG 511:512 TG 511:512 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 48 theme thermogravimetric 483:499 arg1 analysis 501:508 thermogravimetric analysis 483:508 thermogravimetric analysis (TG) 483:513 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 49 theme thermal 195:201 arg1 stability 203:211 thermal stability 195:211 thermal stability 195:211 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 0 50 theme Gum 54:56 arg1 Characteristics 23:37 Structural and Thermal Characteristics 0:37 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 0:77 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 37050276 2 51 theme scanning 529:536 arg1 DSC 551:553 DSC 551:553 DSC 551:553 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 51 theme scanning 529:536 arg1 calorimetry 538:548 differential scanning calorimetry 516:548 differential scanning calorimetry (DSC) 516:554 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 7 52 theme carbon 1341:1346 arg1 presence 1329:1336 the presence 1325:1336 the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition 1325:1455 EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition. 37050276 0 53 theme Tree 49:52 arg1 flexuosa 68:75 Mauritia flexuosa 59:75 Mauritia flexuosa 59:75 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 37050276 0 53 theme Tree 49:52 arg1 Gum 54:56 Buriti Tree Gum 42:56 Buriti Tree Gum (Mauritia flexuosa) 42:76 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 37050276 2 54 theme differential 516:527 arg1 DSC 551:553 DSC 551:553 DSC 551:553 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 54 theme differential 516:527 arg1 calorimetry 538:548 differential scanning calorimetry 516:548 differential scanning calorimetry (DSC) 516:554 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 55 theme molecular 174:182 arg1 structure 184:192 The molecular structure 170:192 The molecular structure 170:192 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 56 dep resonance 407:415 arg1 13C 429:431 13C 429:431 13C 429:431 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 56 dep resonance 407:415 arg1 1H 422:423 NMR 1H 418:423 NMR 1H 418:423 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 57 theme spectroscopic 308:320 arg1 techniques 322:331 spectroscopic techniques 308:331 spectroscopic techniques 308:331 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 4 58 theme maximum 891:897 arg1 peak 911:914 a maximum degradation peak 889:914 a maximum degradation peak at 291.97 °C, with a mass loss of 56.33% 889:955 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 7 59 theme oxygen 1352:1357 arg1 presence 1329:1336 the presence 1325:1336 the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition 1325:1455 EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition. 37050276 6 60 theme amorphous 1249:1257 arg1 nature 1259:1264 the amorphous nature 1245:1264 the amorphous nature of BG that was confirmed by the XRD standard 1245:1309 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 6 61 theme glass 1090:1094 arg1 transition 1096:1105 a glass transition 1088:1105 a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard 1088:1309 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 6 62 dep smooth 1196:1201 arg1 regions 1222:1228 scaly regions 1216:1228 scaly regions 1216:1228 DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. 37050276 4 63 theme Buriti 753:758 arg1 gum 765:767 Buriti tree gum 753:767 Buriti tree gum (BG) 753:772 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 4 63 theme Buriti 753:758 arg1 arabinogalactan 780:794 an arabinogalactan 777:794 an arabinogalactan 777:794 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 4 63 theme Buriti 753:758 arg1 BG 770:771 BG 770:771 BG 770:771 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 3 64 theme Xyl 737:739 arg1 conformers 741:750 Gal and Xyl conformers 729:750 Gal and Xyl conformers 729:750 In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. 37050276 3 65 theme chemical 710:717 arg1 shifts 719:724 chemical shifts 710:724 chemical shifts 710:724 In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. 37050276 0 66 theme Mauritia 59:66 arg1 flexuosa 68:75 Mauritia flexuosa 59:75 Mauritia flexuosa 59:75 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 37050276 0 66 theme Mauritia 59:66 arg1 Gum 54:56 Buriti Tree Gum 42:56 Buriti Tree Gum (Mauritia flexuosa) 42:76 Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa). 37050276 7 67 attach presence 1329:1336 arg2 carbon 1341:1346 carbon 1341:1346 carbon 1341:1346 EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition. 37050276 7 67 attach presence 1329:1336 arg2 calcium 1371:1377 calcium 1371:1377 calcium 1371:1377 EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition. 37050276 7 67 attach presence 1329:1336 arg1 composition 1445:1455 the BG composition 1438:1455 the BG composition 1438:1455 EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition. 37050276 7 67 attach presence 1329:1336 arg2 oxygen 1352:1357 oxygen 1352:1357 oxygen 1352:1357 EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition. 37050276 2 68 theme Fourier-transform 342:358 arg1 FTIR 383:386 FTIR 383:386 FTIR 383:386 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 68 theme Fourier-transform 342:358 arg1 spectroscopy 369:380 Fourier-transform infrared spectroscopy 342:380 Fourier-transform infrared spectroscopy (FTIR) 342:387 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 4 69 theme degradation 899:909 arg1 peak 911:914 a maximum degradation peak 889:914 a maximum degradation peak at 291.97 °C, with a mass loss of 56.33% 889:955 Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. 37050276 2 70 theme X-ray 457:461 arg1 EDS 477:479 EDS 477:479 EDS 477:479 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 37050276 2 70 theme X-ray 457:461 arg1 spectroscopy 463:474 energy-dispersive X-ray spectroscopy 439:474 energy-dispersive X-ray spectroscopy (EDS) 439:480 The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). 36678818 2 0 theme skin 519:522 arg1 layers 524:529 the skin layers 515:529 the skin layers 515:529 Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. 36678818 3 1 theme permeation 717:726 arg1 profile 740:746 their skin permeation enhancement profile 706:746 their skin permeation enhancement profile 706:746 In this study, menthol, L-linalool, bergamot oil, and β-pinene were incorporated in alginate/fucoidan hydrogels to evaluate their skin permeation enhancement profile and assess their influence on the skin organization. 36678818 1 2 from properties 191:200 arg1 field 245:249 the drug delivery field 227:249 the drug delivery field 227:249 Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. 36678818 1 3 theme hydrogel-forming 261:276 arg1 capacities 278:287 hydrogel-forming capacities 261:287 hydrogel-forming capacities 261:287 Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. 36678818 5 4 theme mg 1201:1202 arg1 mg 1176:1177 15 mg out 1173:1181 15 mg out of the initial 75 mg 1173:1202 The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. 36678818 7 5 theme lateral 1644:1650 arg1 packing 1652:1658 less lateral packing 1639:1658 less lateral packing 1639:1658 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 5 6 theme incorporated 1287:1298 arg1 oil 1300:1302 any incorporated oil 1283:1302 any incorporated oil 1283:1302 The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. 36678818 2 7 theme pleasant 547:554 arg1 scent 556:560 a pleasant scent 545:560 a pleasant scent to the formulation 545:579 Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. 36678818 7 8 theme Infrared 1425:1432 arg1 analysis 1454:1461 Infrared micro-spectroscopic analysis 1425:1461 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy 1425:1532 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 6 9 theme calcein 1310:1316 arg1 retention 1318:1326 Skin calcein retention 1305:1326 Skin calcein retention for menthol- and pinene-alginate/fucoidan hydrogels 1305:1378 Skin calcein retention for menthol- and pinene-alginate/fucoidan hydrogels was 15% higher than in the other conditions. 36678818 8 10 theme transdermal 1880:1890 arg1 systems 1901:1907 topical or transdermal delivery systems 1869:1907 topical or transdermal delivery systems 1869:1907 The study highlights the effect of the composition in the design of formulations for topical or transdermal delivery systems. 36678818 4 11 from application 1014:1024 arg1 skin 1033:1036 the skin 1029:1036 the skin 1029:1036 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 4 12 theme uniform 1006:1012 arg1 application 1014:1024 a uniform application 1004:1024 a uniform application in the skin 1004:1036 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 8 13 from effect 1809:1814 arg1 design 1842:1847 the design 1838:1847 the design of formulations for topical or transdermal delivery systems 1838:1907 The study highlights the effect of the composition in the design of formulations for topical or transdermal delivery systems. 36678818 7 14 theme higher 1584:1589 arg1 wavenumber 1591:1600 higher wavenumber 1584:1600 higher wavenumber 1584:1600 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 1 15 theme cutaneous 293:301 arg1 application 303:313 cutaneous application 293:313 cutaneous application towards several dermatological conditions 293:355 Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. 36678818 0 16 theme Essential 116:124 arg1 Oils 126:129 Different Essential Oils 106:129 Different Essential Oils 106:129 Evaluating the Skin Interactions and Permeation of Alginate/Fucoidan Hydrogels Per Se and Associated with Different Essential Oils. 36678818 6 17 theme pinene-alginate/fucoidan 1345:1368 arg1 hydrogels 1370:1378 menthol- and pinene-alginate/fucoidan hydrogels 1332:1378 menthol- and pinene-alginate/fucoidan hydrogels 1332:1378 Skin calcein retention for menthol- and pinene-alginate/fucoidan hydrogels was 15% higher than in the other conditions. 36678818 4 18 theme hydrogel 886:893 arg1 matrix 895:900 the marine-based fucoidan/alginate hydrogel matrix 851:900 the marine-based fucoidan/alginate hydrogel matrix 851:900 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 7 19 theme CH3 1565:1567 arg1 groups 1569:1574 CH3 groups 1565:1574 CH3 groups 1565:1574 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 1 20 theme biological 180:189 arg1 properties 191:200 their biological properties 174:200 their biological properties 174:200 Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. 36678818 0 21 theme Different 106:114 arg1 Oils 126:129 Different Essential Oils 106:129 Different Essential Oils 106:129 Evaluating the Skin Interactions and Permeation of Alginate/Fucoidan Hydrogels Per Se and Associated with Different Essential Oils. 36678818 3 22 theme enhancement 728:738 arg1 profile 740:746 their skin permeation enhancement profile 706:746 their skin permeation enhancement profile 706:746 In this study, menthol, L-linalool, bergamot oil, and β-pinene were incorporated in alginate/fucoidan hydrogels to evaluate their skin permeation enhancement profile and assess their influence on the skin organization. 36678818 3 23 from influence 765:773 arg1 organization 787:798 the skin organization 778:798 the skin organization 778:798 In this study, menthol, L-linalool, bergamot oil, and β-pinene were incorporated in alginate/fucoidan hydrogels to evaluate their skin permeation enhancement profile and assess their influence on the skin organization. 36678818 5 24 theme ex 1043:1044 arg1 assays 1078:1083 The ex vivo Franz diffusion permeation assays 1039:1083 The ex vivo Franz diffusion permeation assays 1039:1083 The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. 36678818 7 25 theme micro-spectroscopic 1434:1452 arg1 analysis 1454:1461 Infrared micro-spectroscopic analysis 1425:1461 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy 1425:1532 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 2 26 dep capacity 476:483 arg1 confer 538:543 confer 538:543 to confer a pleasant scent to the formulation 535:579 Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. 36678818 2 26 dep capacity 476:483 arg1 enhance 488:494 enhance 488:494 to enhance permeation through the skin layers 485:529 Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. 36678818 8 27 theme formulations 1852:1863 arg1 design 1842:1847 the design 1838:1847 the design of formulations for topical or transdermal delivery systems 1838:1907 The study highlights the effect of the composition in the design of formulations for topical or transdermal delivery systems. 36678818 3 28 theme alginate/fucoidan 666:682 arg1 hydrogels 684:692 alginate/fucoidan hydrogels 666:692 alginate/fucoidan hydrogels 666:692 In this study, menthol, L-linalool, bergamot oil, and β-pinene were incorporated in alginate/fucoidan hydrogels to evaluate their skin permeation enhancement profile and assess their influence on the skin organization. 36678818 7 29 dep Fourier 1489:1495 arg1 Transform 1497:1505 Transform 1497:1505 Transform Infrared Microspectroscopy 1497:1532 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 2 30 theme Essential 358:366 arg1 oils 368:371 Essential oils 358:371 Essential oils 358:371 Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. 36678818 5 31 theme diffusion 1057:1065 arg1 assays 1078:1083 The ex vivo Franz diffusion permeation assays 1039:1083 The ex vivo Franz diffusion permeation assays 1039:1083 The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. 36678818 4 32 theme favorable 990:998 arg1 properties 979:988 pseudoplastic rheological properties 953:988 pseudoplastic rheological properties favorable for a uniform application in the skin 953:1036 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 2 33 used used 390:393 arg2 oils 368:371 Essential oils 358:371 Essential oils 358:371 Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. 36678818 8 34 theme topical 1869:1875 arg1 systems 1901:1907 topical or transdermal delivery systems 1869:1907 topical or transdermal delivery systems 1869:1907 The study highlights the effect of the composition in the design of formulations for topical or transdermal delivery systems. 36678818 0 35 theme Skin 15:18 arg1 Interactions 20:31 the Skin Interactions 11:31 the Skin Interactions 11:31 Evaluating the Skin Interactions and Permeation of Alginate/Fucoidan Hydrogels Per Se and Associated with Different Essential Oils. 36678818 1 36 theme several 323:329 arg1 conditions 346:355 several dermatological conditions 323:355 several dermatological conditions 323:355 Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. 36678818 7 37 from cm-1 1693:1696 arg1 band 1680:1683 a band 1678:1683 a band at 1468 cm-1 1678:1696 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 7 38 theme symmetric 1546:1554 arg1 shift 1556:1560 a symmetric shift 1544:1560 a symmetric shift in CH3 groups towards higher wavenumber 1544:1600 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 8 39 theme delivery 1892:1899 arg1 systems 1901:1907 topical or transdermal delivery systems 1869:1907 topical or transdermal delivery systems 1869:1907 The study highlights the effect of the composition in the design of formulations for topical or transdermal delivery systems. 36678818 1 40 theme dermatological 331:344 arg1 conditions 346:355 several dermatological conditions 323:355 several dermatological conditions 323:355 Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. 36678818 5 41 theme permeation 1067:1076 arg1 assays 1078:1083 The ex vivo Franz diffusion permeation assays 1039:1083 The ex vivo Franz diffusion permeation assays 1039:1083 The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. 36678818 4 42 with formulations 935:946 arg1 properties 979:988 pseudoplastic rheological properties 953:988 pseudoplastic rheological properties favorable for a uniform application in the skin 953:1036 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 4 43 with combinations 805:816 arg1 matrix 895:900 the marine-based fucoidan/alginate hydrogel matrix 851:900 the marine-based fucoidan/alginate hydrogel matrix 851:900 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 2 44 theme remarkable 423:432 arg1 properties 445:454 their remarkable biological properties 417:454 their remarkable biological properties 417:454 Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. 36678818 7 45 theme enhancing 1757:1765 arg1 permeation 1772:1781 enhancing skin permeation 1757:1781 enhancing skin permeation 1757:1781 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 4 46 theme oils 841:844 arg1 combinations 805:816 The combinations 801:816 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix 801:900 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 7 47 theme Infrared 1507:1514 arg1 Microspectroscopy 1516:1532 Infrared Microspectroscopy 1507:1532 Infrared Microspectroscopy 1507:1532 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 1 48 theme drug 231:234 arg1 field 245:249 the drug delivery field 227:249 the drug delivery field 227:249 Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. 36678818 7 49 theme skin 1767:1770 arg1 permeation 1772:1781 enhancing skin permeation 1757:1781 enhancing skin permeation 1757:1781 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 6 50 theme other 1407:1411 arg1 conditions 1413:1422 the other conditions 1403:1422 the other conditions 1403:1422 Skin calcein retention for menthol- and pinene-alginate/fucoidan hydrogels was 15% higher than in the other conditions. 36678818 4 51 theme marine-based 855:866 arg1 matrix 895:900 the marine-based fucoidan/alginate hydrogel matrix 851:900 the marine-based fucoidan/alginate hydrogel matrix 851:900 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 6 52 theme menthol- 1332:1339 arg1 hydrogels 1370:1378 menthol- and pinene-alginate/fucoidan hydrogels 1332:1378 menthol- and pinene-alginate/fucoidan hydrogels 1332:1378 Skin calcein retention for menthol- and pinene-alginate/fucoidan hydrogels was 15% higher than in the other conditions. 36678818 3 53 theme skin 782:785 arg1 organization 787:798 the skin organization 778:798 the skin organization 778:798 In this study, menthol, L-linalool, bergamot oil, and β-pinene were incorporated in alginate/fucoidan hydrogels to evaluate their skin permeation enhancement profile and assess their influence on the skin organization. 36678818 5 54 theme initial 1190:1196 arg1 mg 1201:1202 the initial 75 mg 1186:1202 the initial 75 mg 1186:1202 The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. 36678818 4 55 theme fucoidan/alginate 868:884 arg1 matrix 895:900 the marine-based fucoidan/alginate hydrogel matrix 851:900 the marine-based fucoidan/alginate hydrogel matrix 851:900 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 1 56 from application 212:222 arg1 field 245:249 the drug delivery field 227:249 the drug delivery field 227:249 Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. 36678818 5 57 dep ex 1043:1044 arg1 vivo 1046:1049 vivo 1046:1049 vivo 1046:1049 The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. 36678818 6 58 theme Skin 1305:1308 arg1 retention 1318:1326 Skin calcein retention 1305:1326 Skin calcein retention for menthol- and pinene-alginate/fucoidan hydrogels 1305:1378 Skin calcein retention for menthol- and pinene-alginate/fucoidan hydrogels was 15% higher than in the other conditions. 36678818 4 59 theme different 821:829 arg1 oils 841:844 different essential oils 821:844 different essential oils 821:844 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 4 60 theme rheological 967:977 arg1 properties 979:988 pseudoplastic rheological properties 953:988 pseudoplastic rheological properties favorable for a uniform application in the skin 953:1036 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 7 61 theme synchrotron-based 1471:1487 arg1 Fourier 1489:1495 synchrotron-based Fourier 1471:1495 synchrotron-based Fourier Transform Infrared Microspectroscopy 1471:1532 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 1 62 theme Marine 132:137 arg1 polysaccharides 139:153 Marine polysaccharides 132:153 Marine polysaccharides 132:153 Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. 36678818 1 63 theme delivery 236:243 arg1 field 245:249 the drug delivery field 227:249 the drug delivery field 227:249 Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. 36678818 4 64 theme pseudoplastic 953:965 arg1 properties 979:988 pseudoplastic rheological properties 953:988 pseudoplastic rheological properties favorable for a uniform application in the skin 953:1036 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 5 65 theme bergamot-alginate/fucoidan 1117:1142 arg1 hydrogel 1144:1151 bergamot-alginate/fucoidan hydrogel 1117:1151 bergamot-alginate/fucoidan hydrogel 1117:1151 The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. 36678818 5 66 theme Franz 1051:1055 arg1 assays 1078:1083 The ex vivo Franz diffusion permeation assays 1039:1083 The ex vivo Franz diffusion permeation assays 1039:1083 The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. 36678818 7 67 from shift 1556:1560 arg1 groups 1569:1574 CH3 groups 1565:1574 CH3 groups 1565:1574 Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. 36678818 2 68 theme biological 434:443 arg1 properties 445:454 their remarkable biological properties 417:454 their remarkable biological properties 417:454 Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. 36678818 4 69 theme essential 831:839 arg1 oils 841:844 different essential oils 821:844 different essential oils 821:844 The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. 36678818 0 70 theme Hydrogels 69:77 arg1 Permeation 37:46 Permeation 37:46 Permeation of Alginate/Fucoidan Hydrogels Per Se 37:84 Evaluating the Skin Interactions and Permeation of Alginate/Fucoidan Hydrogels Per Se and Associated with Different Essential Oils. 36678818 0 70 theme Hydrogels 69:77 arg1 Interactions 20:31 the Skin Interactions 11:31 the Skin Interactions 11:31 Evaluating the Skin Interactions and Permeation of Alginate/Fucoidan Hydrogels Per Se and Associated with Different Essential Oils. 36678818 3 71 theme skin 712:715 arg1 profile 740:746 their skin permeation enhancement profile 706:746 their skin permeation enhancement profile 706:746 In this study, menthol, L-linalool, bergamot oil, and β-pinene were incorporated in alginate/fucoidan hydrogels to evaluate their skin permeation enhancement profile and assess their influence on the skin organization. 36678818 3 72 theme bergamot 618:625 arg1 oil 627:629 bergamot oil 618:629 bergamot oil 618:629 In this study, menthol, L-linalool, bergamot oil, and β-pinene were incorporated in alginate/fucoidan hydrogels to evaluate their skin permeation enhancement profile and assess their influence on the skin organization. 36678818 8 73 theme composition 1823:1833 arg1 effect 1809:1814 the effect 1805:1814 the effect of the composition in the design of formulations for topical or transdermal delivery systems 1805:1907 The study highlights the effect of the composition in the design of formulations for topical or transdermal delivery systems. 36686576 4 0 from studies 713:719 arg1 brain 743:747 the mouse or human brain 724:747 brain 743:747 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 11 1 dep Discussion 1708:1717 arg1 suggests 1737:1744 suggests 1737:1744 suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective 1737:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 4 2 theme neonatal 675:682 arg1 brain 684:688 the fetal or neonatal brain 662:688 the fetal or neonatal brain 662:688 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 10 3 theme subcellular 1547:1557 arg1 level 1559:1563 the subcellular level 1543:1563 the subcellular level 1543:1563 At the subcellular level, POMGNT1 was mainly co-localized with the Golgi apparatus, but expression in the endoplasmic reticulum and mitochondria could not be excluded. 36686576 11 4 theme physiological 1982:1994 arg1 functions 1996:2004 normal physiological functions 1975:2004 normal physiological functions of the brain from a morphological perspective 1975:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 11 5 theme brain 1797:1801 arg1 regions 1803:1809 various brain regions 1789:1809 various brain regions 1789:1809 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 7 6 theme adult 1098:1102 arg1 brains 1110:1115 normal adult mouse brains 1091:1115 normal adult mouse brains 1091:1115 We also detected the distribution profile of POMGnT1 in normal adult mouse brains by immunohistochemistry and double-immunofluorescence. 36686576 9 7 theme glutamatergic 1464:1476 arg1 neurons 1478:1484 glutamatergic neurons 1464:1484 glutamatergic neurons 1464:1484 In terms of cell type, POMGNT1 was predominantly expressed in neurons and was mainly enriched in glutamatergic neurons; to a lesser extent, it was expressed in glial cells. 36686576 0 8 theme mouse 131:135 arg1 brain 137:141 the normal adult mouse brain 114:141 the normal adult mouse brain 114:141 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 11 9 theme brain 2013:2017 arg1 functions 1996:2004 normal physiological functions 1975:2004 normal physiological functions of the brain from a morphological perspective 1975:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 5 10 theme adult 854:858 arg1 brain 866:870 the normal adult mouse brain 843:870 the normal adult mouse brain 843:870 However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain. 36686576 6 11 theme neuroanatomical 961:975 arg1 regions 977:983 various neuroanatomical regions 953:983 various neuroanatomical regions 953:983 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 11 12 theme morphological 2026:2038 arg1 perspective 2040:2050 a morphological perspective 2024:2050 a morphological perspective 2024:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 4 13 theme fetal 666:670 arg1 brain 684:688 the fetal or neonatal brain 662:688 the fetal or neonatal brain 662:688 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 11 14 theme possible 1940:1947 arg1 involvement 1949:1959 the possible involvement 1936:1959 the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective 1936:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 8 15 theme expression 1316:1325 arg1 levels 1306:1311 high levels 1301:1311 high levels of expression in the cerebral cortex and hippocampus 1301:1364 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 7 16 theme distribution 1056:1067 arg1 profile 1069:1075 the distribution profile 1052:1075 the distribution profile of POMGnT1 1052:1086 We also detected the distribution profile of POMGnT1 in normal adult mouse brains by immunohistochemistry and double-immunofluorescence. 36686576 1 17 theme Introduction 144:155 arg1 POMGNT1 222:228 POMGNT1 222:228 POMGNT1 222:228 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 1 17 theme Introduction 144:155 arg1 β1,2-N-acetylglucosaminyltransferase 182:217 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 144:219 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) 144:229 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 8 18 theme cerebral 1334:1341 arg1 cortex 1343:1348 the cerebral cortex 1330:1348 the cerebral cortex 1330:1348 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 4 19 from expression 637:646 arg1 brain 684:688 the fetal or neonatal brain 662:688 the fetal or neonatal brain 662:688 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 1 20 theme O-linked 165:172 arg1 POMGNT1 222:228 POMGNT1 222:228 POMGNT1 222:228 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 1 20 theme O-linked 165:172 arg1 β1,2-N-acetylglucosaminyltransferase 182:217 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 144:219 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) 144:229 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 0 21 theme β1,2-N-acetylglucosaminyltransferase 72:107 arg1 distribution 31:42 distribution 31:42 distribution 31:42 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 0 21 theme β1,2-N-acetylglucosaminyltransferase 72:107 arg1 expression 16:25 expression 16:25 expression 16:25 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 9 22 theme glial 1527:1531 arg1 cells 1533:1537 glial cells 1527:1537 glial cells 1527:1537 In terms of cell type, POMGNT1 was predominantly expressed in neurons and was mainly enriched in glutamatergic neurons; to a lesser extent, it was expressed in glial cells. 36686576 6 23 theme western 1005:1011 arg1 blotting 1013:1020 western blotting 1005:1020 western blotting 1005:1020 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 0 24 from Analysis 0:7 arg1 brain 137:141 the normal adult mouse brain 114:141 the normal adult mouse brain 114:141 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 6 25 theme cords 996:1000 arg1 brains 943:948 the brains 939:948 the brains of various neuroanatomical regions and spinal cords 939:1000 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 11 26 theme study 1885:1889 arg1 outcomes 1868:1875 the outcomes 1864:1875 the outcomes of this study 1864:1889 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 0 27 theme normal 118:123 arg1 brain 137:141 the normal adult mouse brain 114:141 the normal adult mouse brain 114:141 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 11 28 dep has 1816:1818 arg1 may 1812:1814 may 1812:1814 may 1812:1814 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 11 28 dep has 1816:1818 arg1 expressed 1776:1784 expressed 1776:1784 expressed in various brain regions 1776:1809 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 0 29 theme distribution 31:42 arg1 Analysis 0:7 Analysis 0:7 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 0:142 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 8 30 dep Results 1172:1178 arg1 found 1205:1209 found 1205:1209 found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus 1205:1364 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 5 31 theme POMGNT1 832:838 arg1 expression 818:827 expression 818:827 expression 818:827 However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain. 36686576 5 31 theme POMGNT1 832:838 arg1 distribution 801:812 neuroanatomical distribution 785:812 neuroanatomical distribution 785:812 However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain. 36686576 2 32 from Mutations 284:292 arg1 POMGNT1 297:303 POMGNT1 297:303 POMGNT1 297:303 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 11 33 theme laboratory 1905:1914 arg1 basis 1916:1920 a new laboratory basis 1899:1920 a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective 1899:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 11 34 theme normal 1975:1980 arg1 functions 1996:2004 normal physiological functions 1975:2004 normal physiological functions of the brain from a morphological perspective 1975:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 3 35 theme growing 419:425 arg1 number 427:432 A growing number 417:432 A growing number of studies 417:443 A growing number of studies have shown that defects in POMGNT1 affect neuronal migration and distribution, disrupt basement membranes, and misalign Cajal-Retzius cells. 36686576 10 36 from expression 1628:1637 arg1 reticulum 1658:1666 the endoplasmic reticulum 1642:1666 the endoplasmic reticulum 1642:1666 At the subcellular level, POMGNT1 was mainly co-localized with the Golgi apparatus, but expression in the endoplasmic reticulum and mitochondria could not be excluded. 36686576 10 36 from expression 1628:1637 arg1 mitochondria 1672:1683 mitochondria 1672:1683 mitochondria 1672:1683 At the subcellular level, POMGNT1 was mainly co-localized with the Golgi apparatus, but expression in the endoplasmic reticulum and mitochondria could not be excluded. 36686576 0 37 theme O-linked 55:62 arg1 β1,2-N-acetylglucosaminyltransferase 72:107 protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 47:109 protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 47:109 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 3 38 from defects 461:467 arg1 POMGNT1 472:478 POMGNT1 472:478 POMGNT1 472:478 A growing number of studies have shown that defects in POMGNT1 affect neuronal migration and distribution, disrupt basement membranes, and misalign Cajal-Retzius cells. 36686576 2 39 theme features 359:366 arg1 disease 334:340 muscle-eye-brain (MEB) disease 311:340 muscle-eye-brain (MEB) disease 311:340 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 2 39 theme features 359:366 arg1 aberrations 391:401 anatomical aberrations 380:401 anatomical aberrations in the brain 380:414 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 2 39 theme features 359:366 arg1 features 359:366 the main features 350:366 the main features of which is anatomical aberrations in the brain 350:414 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 2 39 theme features 359:366 arg1 one 343:345 one 343:345 one 343:345 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 9 40 theme type 1384:1387 arg1 terms 1370:1374 terms 1370:1374 terms of cell type 1370:1387 In terms of cell type, POMGNT1 was predominantly expressed in neurons and was mainly enriched in glutamatergic neurons; to a lesser extent, it was expressed in glial cells. 36686576 11 41 theme present 1723:1729 arg1 study 1731:1735 The present study 1719:1735 The present study 1719:1735 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 11 42 theme regional 1825:1832 arg1 specificity 1847:1857 some regional and cellular specificity 1820:1857 some regional and cellular specificity 1820:1857 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 11 43 theme new 1901:1903 arg1 basis 1916:1920 a new laboratory basis 1899:1920 a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective 1899:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 2 44 theme anatomical 380:389 arg1 aberrations 391:401 anatomical aberrations 380:401 anatomical aberrations in the brain 380:414 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 8 45 from hippocampus 1354:1364 arg1 levels 1306:1311 high levels 1301:1311 high levels of expression in the cerebral cortex and hippocampus 1301:1364 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 1 46 theme O-mannosyl 264:273 arg1 glycans 275:281 O-mannosyl glycans 264:281 O-mannosyl glycans 264:281 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 11 47 from functions 1996:2004 arg1 perspective 2040:2050 a morphological perspective 2024:2050 a morphological perspective 2024:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 6 48 from expression 897:906 arg1 brains 943:948 the brains 939:948 the brains of various neuroanatomical regions and spinal cords 939:1000 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 8 49 theme present 1187:1193 arg1 study 1195:1199 the present study 1183:1199 the present study 1183:1199 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 6 50 theme POMGNT1 911:917 arg1 expression 897:906 the expression 893:906 the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords 893:1000 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 11 51 from involvement 1949:1959 arg1 functions 1996:2004 normal physiological functions 1975:2004 normal physiological functions of the brain from a morphological perspective 1975:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 11 52 theme cellular 1838:1845 arg1 specificity 1847:1857 some regional and cellular specificity 1820:1857 some regional and cellular specificity 1820:1857 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 7 53 theme mouse 1104:1108 arg1 brains 1110:1115 normal adult mouse brains 1091:1115 normal adult mouse brains 1091:1115 We also detected the distribution profile of POMGnT1 in normal adult mouse brains by immunohistochemistry and double-immunofluorescence. 36686576 2 54 theme muscle-eye-brain 311:326 arg1 disease 334:340 muscle-eye-brain (MEB) disease 311:340 muscle-eye-brain (MEB) disease 311:340 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 2 54 theme muscle-eye-brain 311:326 arg1 MEB 329:331 MEB 329:331 MEB 329:331 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 2 54 theme muscle-eye-brain 311:326 arg1 features 359:366 the main features 350:366 the main features of which is anatomical aberrations in the brain 350:414 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 2 54 theme muscle-eye-brain 311:326 arg1 one 343:345 one 343:345 one 343:345 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 8 55 theme various 1266:1272 arg1 regions 1274:1280 various regions 1266:1280 various regions of the brain 1266:1293 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 4 56 from distribution 620:631 arg1 brain 684:688 the fetal or neonatal brain 662:688 the fetal or neonatal brain 662:688 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 7 57 theme normal 1091:1096 arg1 brains 1110:1115 normal adult mouse brains 1091:1115 normal adult mouse brains 1091:1115 We also detected the distribution profile of POMGnT1 in normal adult mouse brains by immunohistochemistry and double-immunofluorescence. 36686576 6 58 theme spinal 989:994 arg1 cords 996:1000 spinal cords 989:1000 spinal cords 989:1000 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 5 59 dep distribution 801:812 arg1 the 781:783 the 781:783 the 781:783 However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain. 36686576 7 60 theme POMGnT1 1080:1086 arg1 profile 1069:1075 the distribution profile 1052:1075 the distribution profile of POMGnT1 1052:1086 We also detected the distribution profile of POMGnT1 in normal adult mouse brains by immunohistochemistry and double-immunofluorescence. 36686576 3 61 theme Cajal-Retzius 565:577 arg1 cells 579:583 Cajal-Retzius cells 565:583 Cajal-Retzius cells 565:583 A growing number of studies have shown that defects in POMGNT1 affect neuronal migration and distribution, disrupt basement membranes, and misalign Cajal-Retzius cells. 36686576 5 62 theme normal 847:852 arg1 brain 866:870 the normal adult mouse brain 843:870 the normal adult mouse brain 843:870 However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain. 36686576 8 63 theme POMGNT1-positive 1216:1231 arg1 cells 1233:1237 POMGNT1-positive cells 1216:1237 POMGNT1-positive cells 1216:1237 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 6 64 theme regions 977:983 arg1 brains 943:948 the brains 939:948 the brains of various neuroanatomical regions and spinal cords 939:1000 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 4 65 theme POMGNT1 651:657 arg1 expression 637:646 expression 637:646 expression 637:646 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 4 65 theme POMGNT1 651:657 arg1 distribution 620:631 distribution 620:631 distribution 620:631 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 11 66 theme various 1789:1795 arg1 regions 1803:1809 various brain regions 1789:1809 various brain regions 1789:1809 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 5 67 theme mouse 860:864 arg1 brain 866:870 the normal adult mouse brain 843:870 the normal adult mouse brain 843:870 However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain. 36686576 6 68 theme various 953:959 arg1 regions 977:983 various neuroanatomical regions 953:983 various neuroanatomical regions 953:983 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 10 69 theme Golgi 1607:1611 arg1 apparatus 1613:1621 the Golgi apparatus 1603:1621 the Golgi apparatus 1603:1621 At the subcellular level, POMGNT1 was mainly co-localized with the Golgi apparatus, but expression in the endoplasmic reticulum and mitochondria could not be excluded. 36686576 9 70 theme lesser 1492:1497 arg1 extent 1499:1504 a lesser extent 1490:1504 a lesser extent 1490:1504 In terms of cell type, POMGNT1 was predominantly expressed in neurons and was mainly enriched in glutamatergic neurons; to a lesser extent, it was expressed in glial cells. 36686576 4 71 theme mouse 728:732 arg1 brain 743:747 the mouse or human brain 724:747 brain 743:747 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 11 72 theme POMGNT1 1964:1970 arg1 involvement 1949:1959 the possible involvement 1936:1959 the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective 1936:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 11 73 contain has 1816:1818 arg1 POMGNT1 1751:1757 POMGNT1 1751:1757 POMGNT1 1751:1757 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 11 73 contain has 1816:1818 arg2 specificity 1847:1857 some regional and cellular specificity 1820:1857 some regional and cellular specificity 1820:1857 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 4 74 theme human 737:741 arg1 brain 743:747 the mouse or human brain 724:747 brain 743:747 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 0 75 theme mannose 64:70 arg1 β1,2-N-acetylglucosaminyltransferase 72:107 protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 47:109 protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 47:109 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 4 76 dep distribution 620:631 arg1 the 616:618 the 616:618 the 616:618 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 1 77 theme Protein 157:163 arg1 POMGNT1 222:228 POMGNT1 222:228 POMGNT1 222:228 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 1 77 theme Protein 157:163 arg1 β1,2-N-acetylglucosaminyltransferase 182:217 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 144:219 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) 144:229 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 0 78 from expression 16:25 arg1 brain 137:141 the normal adult mouse brain 114:141 the normal adult mouse brain 114:141 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 4 79 theme neurodevelopmental 694:711 arg1 studies 713:719 neurodevelopmental studies 694:719 neurodevelopmental studies in the mouse or human brain 694:747 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 5 80 from expression 818:827 arg1 brain 866:870 the normal adult mouse brain 843:870 the normal adult mouse brain 843:870 However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain. 36686576 1 81 theme mannose 174:180 arg1 POMGNT1 222:228 POMGNT1 222:228 POMGNT1 222:228 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 1 81 theme mannose 174:180 arg1 β1,2-N-acetylglucosaminyltransferase 182:217 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 144:219 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) 144:229 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 11 82 from perspective 2040:2050 arg1 functions 1996:2004 normal physiological functions 1975:2004 normal physiological functions of the brain from a morphological perspective 1975:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 11 82 from perspective 2040:2050 arg1 brain 2013:2017 the brain 2009:2017 the brain from a morphological perspective 2009:2050 Discussion The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective. 36686576 5 83 from distribution 801:812 arg1 brain 866:870 the normal adult mouse brain 843:870 the normal adult mouse brain 843:870 However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain. 36686576 8 84 from expression 1316:1325 arg1 hippocampus 1354:1364 hippocampus 1354:1364 hippocampus 1354:1364 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 8 84 from expression 1316:1325 arg1 cortex 1343:1348 the cerebral cortex 1330:1348 the cerebral cortex 1330:1348 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 0 85 theme adult 125:129 arg1 brain 137:141 the normal adult mouse brain 114:141 the normal adult mouse brain 114:141 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 8 86 theme brain 1289:1293 arg1 regions 1274:1280 various regions 1266:1280 various regions of the brain 1266:1293 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 0 87 from distribution 31:42 arg1 brain 137:141 the normal adult mouse brain 114:141 the normal adult mouse brain 114:141 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 8 88 from cortex 1343:1348 arg1 levels 1306:1311 high levels 1301:1311 high levels of expression in the cerebral cortex and hippocampus 1301:1364 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 3 89 theme studies 437:443 arg1 number 427:432 A growing number 417:432 A growing number of studies 417:443 A growing number of studies have shown that defects in POMGNT1 affect neuronal migration and distribution, disrupt basement membranes, and misalign Cajal-Retzius cells. 36686576 0 90 theme expression 16:25 arg1 Analysis 0:7 Analysis 0:7 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 0:142 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 8 91 from levels 1306:1311 arg1 hippocampus 1354:1364 hippocampus 1354:1364 hippocampus 1354:1364 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 8 91 from levels 1306:1311 arg1 cortex 1343:1348 the cerebral cortex 1330:1348 the cerebral cortex 1330:1348 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 4 92 theme Several 586:592 arg1 studies 594:600 Several studies 586:600 Several studies 586:600 Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. 36686576 5 93 theme neuroanatomical 785:799 arg1 distribution 801:812 neuroanatomical distribution 785:812 neuroanatomical distribution 785:812 However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain. 36686576 8 94 theme high 1301:1304 arg1 levels 1306:1311 high levels 1301:1311 high levels of expression in the cerebral cortex and hippocampus 1301:1364 Results In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. 36686576 6 95 dep Methods 873:879 arg1 analyzed 884:891 analyzed 884:891 analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR 884:1032 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 1 96 link O-linked 165:172 arg1 POMGNT1 222:228 POMGNT1 222:228 POMGNT1 222:228 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 1 96 link O-linked 165:172 arg1 β1,2-N-acetylglucosaminyltransferase 182:217 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 144:219 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) 144:229 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36686576 6 97 dep POMGNT1 911:917 arg1 protein 928:934 protein 928:934 protein 928:934 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 6 97 dep POMGNT1 911:917 arg1 mRNA 919:922 mRNA 919:922 mRNA 919:922 Methods We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. 36686576 10 98 theme endoplasmic 1646:1656 arg1 reticulum 1658:1666 the endoplasmic reticulum 1642:1666 the endoplasmic reticulum 1642:1666 At the subcellular level, POMGNT1 was mainly co-localized with the Golgi apparatus, but expression in the endoplasmic reticulum and mitochondria could not be excluded. 36686576 0 99 theme protein 47:53 arg1 β1,2-N-acetylglucosaminyltransferase 72:107 protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 47:109 protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 47:109 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 9 100 theme cell 1379:1382 arg1 type 1384:1387 cell type 1379:1387 cell type 1379:1387 In terms of cell type, POMGNT1 was predominantly expressed in neurons and was mainly enriched in glutamatergic neurons; to a lesser extent, it was expressed in glial cells. 36686576 2 101 from aberrations 391:401 arg1 brain 410:414 the brain 406:414 the brain 406:414 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 2 102 theme main 354:357 arg1 features 359:366 the main features 350:366 the main features of which is anatomical aberrations in the brain 350:414 Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. 36686576 0 103 link O-linked 55:62 arg1 β1,2-N-acetylglucosaminyltransferase 72:107 protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 47:109 protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 47:109 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 3 104 theme neuronal 487:494 arg1 migration 496:504 migration 496:504 migration 496:504 A growing number of studies have shown that defects in POMGNT1 affect neuronal migration and distribution, disrupt basement membranes, and misalign Cajal-Retzius cells. 36686576 0 105 from brain 137:141 arg1 Analysis 0:7 Analysis 0:7 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 0:142 Analysis of the expression and distribution of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain. 36686576 3 106 theme basement 532:539 arg1 membranes 541:549 basement membranes 532:549 basement membranes 532:549 A growing number of studies have shown that defects in POMGNT1 affect neuronal migration and distribution, disrupt basement membranes, and misalign Cajal-Retzius cells. 36686576 1 107 theme glycans 275:281 arg1 elongation 250:259 the elongation 246:259 the elongation of O-mannosyl glycans 246:281 Introduction Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. 36265712 5 0 from decrease 1051:1058 arg1 aromaticity 1071:1081 overall aromaticity 1063:1081 overall aromaticity 1063:1081 Also, due to the degradation of humic-like substances, the accumulation of protein-like substances was observed from upstream to downstream areas, corresponding to an apparent decrease in overall aromaticity. 36265712 1 1 theme fluxes 271:276 arg1 quality 216:222 quality 216:222 quality 216:222 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 1 1 theme fluxes 271:276 arg1 quantity 228:235 quantity 228:235 quantity 228:235 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 11 2 theme humic-like 2137:2146 arg1 substances 2148:2157 macromolecular humic-like substances 2122:2157 macromolecular humic-like substances 2122:2157 This work unveils the evolution of DOM in an effluent-dominated river and the influence of the degradation of macromolecular humic-like substances on r/K-strategists. 36265712 1 3 from rivers 281:286 arg1 quality 216:222 quality 216:222 quality 216:222 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 1 3 from rivers 281:286 arg1 quantity 228:235 quantity 228:235 quantity 228:235 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 5 4 theme substances 963:972 arg1 accumulation 934:945 the accumulation 930:945 the accumulation of protein-like substances 930:972 Also, due to the degradation of humic-like substances, the accumulation of protein-like substances was observed from upstream to downstream areas, corresponding to an apparent decrease in overall aromaticity. 36265712 1 5 from fluxes 271:276 arg1 rivers 281:286 rivers 281:286 rivers 281:286 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 3 6 theme effluent-dominated 594:611 arg1 river 613:617 an effluent-dominated river 591:617 an effluent-dominated river 591:617 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 5 7 theme substances 918:927 arg1 degradation 892:902 the degradation 888:902 the degradation of humic-like substances 888:927 Also, due to the degradation of humic-like substances, the accumulation of protein-like substances was observed from upstream to downstream areas, corresponding to an apparent decrease in overall aromaticity. 36265712 8 8 theme Actinobacteria 1537:1550 arg1 degradation 1503:1513 the degradation 1499:1513 the degradation of Proteobacteria and Actinobacteria (K-strategists) 1499:1566 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 11 9 from influence 2090:2098 arg1 r/K-strategists 2162:2176 r/K-strategists 2162:2176 r/K-strategists 2162:2176 This work unveils the evolution of DOM in an effluent-dominated river and the influence of the degradation of macromolecular humic-like substances on r/K-strategists. 36265712 0 10 theme composition 127:137 arg1 variations 74:83 variations 74:83 variations of the dissolved organic matter molecular composition 74:137 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 10 11 theme protein-like 1914:1925 arg1 substances 1927:1936 protein-like substances 1914:1936 protein-like substances 1914:1936 With the decrease of macromolecular humic-like substances and the increase of protein-like substances, river microbial communities shifted from K-strategists to r-strategists. 36265712 3 12 dep abundance 668:676 arg1 strategies 692:701 strategies 692:701 strategies 692:701 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 3 12 dep abundance 668:676 arg1 the 664:666 the 664:666 the 664:666 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 9 13 theme relative 1816:1823 arg1 abundance 1825:1833 their relative abundance 1810:1833 their relative abundance 1810:1833 Proteins and polysaccharides (15 kDa < MW < 35 kDa, MW < 6 kDa) were more easily utilized by Firmicutes and Bacteroidetes (r-strategists), leading to an increase in their relative abundance. 36265712 7 14 from changes 1299:1305 arg1 composition 1314:1324 DOM composition 1310:1324 DOM composition 1310:1324 The response of bacterial and Actinobacteria communities to the changes in DOM composition was more prominent as compared to that of eukaryotic. 36265712 8 15 theme multivariate 1389:1400 arg1 analysis 1414:1421 multivariate statistical analysis 1389:1421 multivariate statistical analysis 1389:1421 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 10 16 theme macromolecular 1857:1870 arg1 substances 1883:1892 macromolecular humic-like substances 1857:1892 macromolecular humic-like substances 1857:1892 With the decrease of macromolecular humic-like substances and the increase of protein-like substances, river microbial communities shifted from K-strategists to r-strategists. 36265712 6 17 theme Actinobacteria 1112:1125 arg1 abundance 1088:1096 The abundance 1084:1096 The abundance of bacterial, Actinobacteria, and eukaryotic 1084:1141 The abundance of bacterial, Actinobacteria, and eukaryotic was higher in the upstream and midstream areas but relatively lower in the downstream area. 36265712 6 17 theme Actinobacteria 1112:1125 arg1 higher 1147:1152 higher 1147:1152 higher 1147:1152 The abundance of bacterial, Actinobacteria, and eukaryotic was higher in the upstream and midstream areas but relatively lower in the downstream area. 36265712 0 18 theme lifestyle 50:58 arg1 strategies 60:69 the microbial community lifestyle strategies 26:69 the microbial community lifestyle strategies 26:69 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 1 19 theme lifestyle 325:333 arg1 strategies 335:344 lifestyle strategies 325:344 lifestyle strategies 325:344 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 7 20 theme bacterial 1251:1259 arg1 communities 1280:1290 bacterial and Actinobacteria communities 1251:1290 bacterial and Actinobacteria communities 1251:1290 The response of bacterial and Actinobacteria communities to the changes in DOM composition was more prominent as compared to that of eukaryotic. 36265712 6 21 theme bacterial 1101:1109 arg1 abundance 1088:1096 The abundance 1084:1096 The abundance of bacterial, Actinobacteria, and eukaryotic 1084:1141 The abundance of bacterial, Actinobacteria, and eukaryotic was higher in the upstream and midstream areas but relatively lower in the downstream area. 36265712 6 21 theme bacterial 1101:1109 arg1 higher 1147:1152 higher 1147:1152 higher 1147:1152 The abundance of bacterial, Actinobacteria, and eukaryotic was higher in the upstream and midstream areas but relatively lower in the downstream area. 36265712 2 22 from strategies 453:462 arg1 rivers 486:491 effluent-dominated rivers 467:491 effluent-dominated rivers 467:491 However, relationships between DOM molecular composition and microbial lifestyle strategies in effluent-dominated rivers are poorly understood. 36265712 7 23 theme DOM 1310:1312 arg1 composition 1314:1324 DOM composition 1310:1324 DOM composition 1310:1324 The response of bacterial and Actinobacteria communities to the changes in DOM composition was more prominent as compared to that of eukaryotic. 36265712 5 24 theme upstream 992:999 arg1 areas 1015:1019 upstream to downstream areas 992:1019 upstream to downstream areas 992:1019 Also, due to the degradation of humic-like substances, the accumulation of protein-like substances was observed from upstream to downstream areas, corresponding to an apparent decrease in overall aromaticity. 36265712 10 25 theme microbial 1945:1953 arg1 communities 1955:1965 river microbial communities 1939:1965 river microbial communities 1939:1965 With the decrease of macromolecular humic-like substances and the increase of protein-like substances, river microbial communities shifted from K-strategists to r-strategists. 36265712 4 26 theme effluent-dominated 842:859 arg1 DOM 870:872 effluent-dominated riverine DOM 842:872 effluent-dominated riverine DOM 842:872 Results demonstrated that macromolecular (MW > 35 kDa) humic-like substances constituted the major components of effluent-dominated riverine DOM. 36265712 1 27 theme communities 359:369 arg1 diversity 311:319 diversity 311:319 diversity 311:319 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 1 27 theme communities 359:369 arg1 strategies 335:344 lifestyle strategies 325:344 lifestyle strategies 325:344 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 9 28 from increase 1798:1805 arg1 abundance 1825:1833 their relative abundance 1810:1833 their relative abundance 1810:1833 Proteins and polysaccharides (15 kDa < MW < 35 kDa, MW < 6 kDa) were more easily utilized by Firmicutes and Bacteroidetes (r-strategists), leading to an increase in their relative abundance. 36265712 11 29 theme effluent-dominated 2057:2074 arg1 river 2076:2080 an effluent-dominated river 2054:2080 an effluent-dominated river 2054:2080 This work unveils the evolution of DOM in an effluent-dominated river and the influence of the degradation of macromolecular humic-like substances on r/K-strategists. 36265712 4 30 theme DOM 870:872 arg1 components 828:837 the major components 818:837 the major components of effluent-dominated riverine DOM 818:872 Results demonstrated that macromolecular (MW > 35 kDa) humic-like substances constituted the major components of effluent-dominated riverine DOM. 36265712 2 31 theme molecular 407:415 arg1 composition 417:427 DOM molecular composition 403:427 DOM molecular composition 403:427 However, relationships between DOM molecular composition and microbial lifestyle strategies in effluent-dominated rivers are poorly understood. 36265712 0 32 theme dissolved 92:100 arg1 composition 127:137 the dissolved organic matter molecular composition 88:137 the dissolved organic matter molecular composition 88:137 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 6 33 theme upstream 1161:1168 arg1 areas 1184:1188 the upstream and midstream areas 1157:1188 areas 1184:1188 The abundance of bacterial, Actinobacteria, and eukaryotic was higher in the upstream and midstream areas but relatively lower in the downstream area. 36265712 7 34 theme Actinobacteria 1265:1278 arg1 communities 1280:1290 bacterial and Actinobacteria communities 1251:1290 bacterial and Actinobacteria communities 1251:1290 The response of bacterial and Actinobacteria communities to the changes in DOM composition was more prominent as compared to that of eukaryotic. 36265712 2 35 theme lifestyle 443:451 arg1 strategies 453:462 microbial lifestyle strategies 433:462 microbial lifestyle strategies 433:462 However, relationships between DOM molecular composition and microbial lifestyle strategies in effluent-dominated rivers are poorly understood. 36265712 8 36 from decrease 1584:1591 arg1 abundance 1611:1619 their relative abundance 1596:1619 their relative abundance along the river course 1596:1642 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 5 37 theme apparent 1042:1049 arg1 decrease 1051:1058 an apparent decrease 1039:1058 an apparent decrease in overall aromaticity 1039:1081 Also, due to the degradation of humic-like substances, the accumulation of protein-like substances was observed from upstream to downstream areas, corresponding to an apparent decrease in overall aromaticity. 36265712 11 38 theme DOM 2047:2049 arg1 evolution 2034:2042 the evolution 2030:2042 the evolution of DOM 2030:2049 This work unveils the evolution of DOM in an effluent-dominated river and the influence of the degradation of macromolecular humic-like substances on r/K-strategists. 36265712 0 39 theme microbial 30:38 arg1 strategies 60:69 the microbial community lifestyle strategies 26:69 the microbial community lifestyle strategies 26:69 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 9 40 used utilized 1726:1733 arg2 MW < 6 kDa 1697:1706 MW < 6 kDa 1697:1706 MW < 6 kDa 1697:1706 Proteins and polysaccharides (15 kDa < MW < 35 kDa, MW < 6 kDa) were more easily utilized by Firmicutes and Bacteroidetes (r-strategists), leading to an increase in their relative abundance. 36265712 9 40 used utilized 1726:1733 arg2 polysaccharides 1658:1672 polysaccharides 1658:1672 polysaccharides 1658:1672 Proteins and polysaccharides (15 kDa < MW < 35 kDa, MW < 6 kDa) were more easily utilized by Firmicutes and Bacteroidetes (r-strategists), leading to an increase in their relative abundance. 36265712 9 40 used utilized 1726:1733 arg2 Proteins 1645:1652 Proteins 1645:1652 Proteins 1645:1652 Proteins and polysaccharides (15 kDa < MW < 35 kDa, MW < 6 kDa) were more easily utilized by Firmicutes and Bacteroidetes (r-strategists), leading to an increase in their relative abundance. 36265712 3 41 theme communities 716:726 arg1 lifestyle 682:690 lifestyle 682:690 lifestyle 682:690 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 3 41 theme communities 716:726 arg1 abundance 668:676 abundance 668:676 abundance 668:676 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 8 42 from decrease 1428:1435 arg1 MW > 35 kDa 1461:1471 MW > 35 kDa 1461:1471 MW > 35 kDa 1461:1471 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 8 42 from decrease 1428:1435 arg1 components 1449:1458 aromatic components 1440:1458 aromatic components (MW > 35 kDa) 1440:1472 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 1 43 theme organic 250:256 arg1 DOM 266:268 DOM 266:268 DOM 266:268 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 1 43 theme organic 250:256 arg1 matter 258:263 dissolved organic matter 240:263 dissolved organic matter (DOM) fluxes in rivers 240:286 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 7 44 theme communities 1280:1290 arg1 response 1239:1246 The response 1235:1246 The response of bacterial and Actinobacteria communities to the changes in DOM composition 1235:1324 The response of bacterial and Actinobacteria communities to the changes in DOM composition was more prominent as compared to that of eukaryotic. 36265712 7 44 theme communities 1280:1290 arg1 prominent 1335:1343 prominent 1335:1343 prominent 1335:1343 The response of bacterial and Actinobacteria communities to the changes in DOM composition was more prominent as compared to that of eukaryotic. 36265712 6 45 theme midstream 1174:1182 arg1 areas 1184:1188 the upstream and midstream areas 1157:1188 areas 1184:1188 The abundance of bacterial, Actinobacteria, and eukaryotic was higher in the upstream and midstream areas but relatively lower in the downstream area. 36265712 3 46 from variations 544:553 arg1 composition 576:586 composition 576:586 composition 576:586 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 3 46 from variations 544:553 arg1 structure 562:570 DOM structure 558:570 DOM structure 558:570 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 11 47 theme substances 2148:2157 arg1 degradation 2107:2117 the degradation 2103:2117 the degradation of macromolecular humic-like substances 2103:2157 This work unveils the evolution of DOM in an effluent-dominated river and the influence of the degradation of macromolecular humic-like substances on r/K-strategists. 36265712 11 48 theme macromolecular 2122:2135 arg1 substances 2148:2157 macromolecular humic-like substances 2122:2157 macromolecular humic-like substances 2122:2157 This work unveils the evolution of DOM in an effluent-dominated river and the influence of the degradation of macromolecular humic-like substances on r/K-strategists. 36265712 3 49 theme river 613:617 arg1 composition 576:586 composition 576:586 composition 576:586 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 3 49 theme river 613:617 arg1 structure 562:570 DOM structure 558:570 DOM structure 558:570 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 5 50 theme protein-like 950:961 arg1 substances 963:972 protein-like substances 950:972 protein-like substances 950:972 Also, due to the degradation of humic-like substances, the accumulation of protein-like substances was observed from upstream to downstream areas, corresponding to an apparent decrease in overall aromaticity. 36265712 11 51 from river 2076:2080 arg1 r/K-strategists 2162:2176 r/K-strategists 2162:2176 r/K-strategists 2162:2176 This work unveils the evolution of DOM in an effluent-dominated river and the influence of the degradation of macromolecular humic-like substances on r/K-strategists. 36265712 0 52 theme molecular 117:125 arg1 composition 127:137 the dissolved organic matter molecular composition 88:137 the dissolved organic matter molecular composition 88:137 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 10 53 theme substances 1883:1892 arg1 increase 1902:1909 the increase 1898:1909 the increase of protein-like substances 1898:1936 With the decrease of macromolecular humic-like substances and the increase of protein-like substances, river microbial communities shifted from K-strategists to r-strategists. 36265712 10 53 theme substances 1883:1892 arg1 decrease 1845:1852 the decrease 1841:1852 the decrease of macromolecular humic-like substances 1841:1892 With the decrease of macromolecular humic-like substances and the increase of protein-like substances, river microbial communities shifted from K-strategists to r-strategists. 36265712 5 54 theme humic-like 907:916 arg1 substances 918:927 humic-like substances 907:927 humic-like substances 907:927 Also, due to the degradation of humic-like substances, the accumulation of protein-like substances was observed from upstream to downstream areas, corresponding to an apparent decrease in overall aromaticity. 36265712 10 55 theme substances 1927:1936 arg1 increase 1902:1909 the increase 1898:1909 the increase of protein-like substances 1898:1936 With the decrease of macromolecular humic-like substances and the increase of protein-like substances, river microbial communities shifted from K-strategists to r-strategists. 36265712 10 55 theme substances 1927:1936 arg1 decrease 1845:1852 the decrease 1841:1852 the decrease of macromolecular humic-like substances 1841:1892 With the decrease of macromolecular humic-like substances and the increase of protein-like substances, river microbial communities shifted from K-strategists to r-strategists. 36265712 0 56 theme effluent-dominated 148:165 arg1 river 167:171 an effluent-dominated river 145:171 an effluent-dominated river 145:171 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 1 57 from quantity 228:235 arg1 rivers 281:286 rivers 281:286 rivers 281:286 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 4 58 theme MW > 35 kDa 771:781 arg1 substances 795:804 macromolecular (MW > 35 kDa) humic-like substances 755:804 macromolecular (MW > 35 kDa) humic-like substances 755:804 Results demonstrated that macromolecular (MW > 35 kDa) humic-like substances constituted the major components of effluent-dominated riverine DOM. 36265712 11 59 theme degradation 2107:2117 arg1 river 2076:2080 an effluent-dominated river 2054:2080 an effluent-dominated river 2054:2080 This work unveils the evolution of DOM in an effluent-dominated river and the influence of the degradation of macromolecular humic-like substances on r/K-strategists. 36265712 11 59 theme degradation 2107:2117 arg1 influence 2090:2098 the influence 2086:2098 the influence of the degradation of macromolecular humic-like substances on r/K-strategists 2086:2176 This work unveils the evolution of DOM in an effluent-dominated river and the influence of the degradation of macromolecular humic-like substances on r/K-strategists. 36265712 1 60 from quality 216:222 arg1 rivers 281:286 rivers 281:286 rivers 281:286 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 4 61 theme humic-like 784:793 arg1 substances 795:804 macromolecular (MW > 35 kDa) humic-like substances 755:804 macromolecular (MW > 35 kDa) humic-like substances 755:804 Results demonstrated that macromolecular (MW > 35 kDa) humic-like substances constituted the major components of effluent-dominated riverine DOM. 36265712 0 62 theme strategies 60:69 arg1 role 18:21 the role 14:21 the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition 14:137 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 10 63 theme river 1939:1943 arg1 communities 1955:1965 river microbial communities 1939:1965 river microbial communities 1939:1965 With the decrease of macromolecular humic-like substances and the increase of protein-like substances, river microbial communities shifted from K-strategists to r-strategists. 36265712 0 64 from role 18:21 arg1 variations 74:83 variations 74:83 variations of the dissolved organic matter molecular composition 74:137 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 8 65 theme statistical 1402:1412 arg1 analysis 1414:1421 multivariate statistical analysis 1389:1421 multivariate statistical analysis 1389:1421 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 0 66 theme matter 110:115 arg1 composition 127:137 the dissolved organic matter molecular composition 88:137 the dissolved organic matter molecular composition 88:137 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 8 67 theme relative 1602:1609 arg1 abundance 1611:1619 their relative abundance 1596:1619 their relative abundance along the river course 1596:1642 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 4 68 theme macromolecular 755:768 arg1 substances 795:804 macromolecular (MW > 35 kDa) humic-like substances 755:804 macromolecular (MW > 35 kDa) humic-like substances 755:804 Results demonstrated that macromolecular (MW > 35 kDa) humic-like substances constituted the major components of effluent-dominated riverine DOM. 36265712 1 69 theme microbial 349:357 arg1 communities 359:369 microbial communities 349:369 microbial communities 349:369 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 10 70 theme humic-like 1872:1881 arg1 substances 1883:1892 macromolecular humic-like substances 1857:1892 macromolecular humic-like substances 1857:1892 With the decrease of macromolecular humic-like substances and the increase of protein-like substances, river microbial communities shifted from K-strategists to r-strategists. 36265712 1 71 dep diversity 311:319 arg1 the 307:309 the 307:309 the 307:309 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 0 72 theme organic 102:108 arg1 composition 127:137 the dissolved organic matter molecular composition 88:137 the dissolved organic matter molecular composition 88:137 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 5 73 theme overall 1063:1069 arg1 aromaticity 1071:1081 overall aromaticity 1063:1081 overall aromaticity 1063:1081 Also, due to the degradation of humic-like substances, the accumulation of protein-like substances was observed from upstream to downstream areas, corresponding to an apparent decrease in overall aromaticity. 36265712 8 74 theme river 1631:1635 arg1 course 1637:1642 the river course 1627:1642 the river course 1627:1642 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 4 75 theme riverine 861:868 arg1 DOM 870:872 effluent-dominated riverine DOM 842:872 effluent-dominated riverine DOM 842:872 Results demonstrated that macromolecular (MW > 35 kDa) humic-like substances constituted the major components of effluent-dominated riverine DOM. 36265712 2 76 theme DOM 403:405 arg1 composition 417:427 DOM molecular composition 403:427 DOM molecular composition 403:427 However, relationships between DOM molecular composition and microbial lifestyle strategies in effluent-dominated rivers are poorly understood. 36265712 2 77 theme effluent-dominated 467:484 arg1 rivers 486:491 effluent-dominated rivers 467:491 effluent-dominated rivers 467:491 However, relationships between DOM molecular composition and microbial lifestyle strategies in effluent-dominated rivers are poorly understood. 36265712 5 78 dep upstream 992:999 arg1 downstream 1004:1013 downstream 1004:1013 downstream 1004:1013 Also, due to the degradation of humic-like substances, the accumulation of protein-like substances was observed from upstream to downstream areas, corresponding to an apparent decrease in overall aromaticity. 36265712 5 78 dep upstream 992:999 arg1 to 1001:1002 to 1001:1002 to 1001:1002 Also, due to the degradation of humic-like substances, the accumulation of protein-like substances was observed from upstream to downstream areas, corresponding to an apparent decrease in overall aromaticity. 36265712 4 79 theme major 822:826 arg1 components 828:837 the major components 818:837 the major components of effluent-dominated riverine DOM 818:872 Results demonstrated that macromolecular (MW > 35 kDa) humic-like substances constituted the major components of effluent-dominated riverine DOM. 36265712 2 80 theme microbial 433:441 arg1 strategies 453:462 microbial lifestyle strategies 433:462 microbial lifestyle strategies 433:462 However, relationships between DOM molecular composition and microbial lifestyle strategies in effluent-dominated rivers are poorly understood. 36265712 6 81 theme eukaryotic 1132:1141 arg1 abundance 1088:1096 The abundance 1084:1096 The abundance of bacterial, Actinobacteria, and eukaryotic 1084:1141 The abundance of bacterial, Actinobacteria, and eukaryotic was higher in the upstream and midstream areas but relatively lower in the downstream area. 36265712 6 81 theme eukaryotic 1132:1141 arg1 higher 1147:1152 higher 1147:1152 higher 1147:1152 The abundance of bacterial, Actinobacteria, and eukaryotic was higher in the upstream and midstream areas but relatively lower in the downstream area. 36265712 0 82 theme community 40:48 arg1 strategies 60:69 the microbial community lifestyle strategies 26:69 the microbial community lifestyle strategies 26:69 Insights into the role of the microbial community lifestyle strategies in variations of the dissolved organic matter molecular composition along an effluent-dominated river. 36265712 6 83 theme downstream 1218:1227 arg1 area 1229:1232 the downstream area 1214:1232 the downstream area 1214:1232 The abundance of bacterial, Actinobacteria, and eukaryotic was higher in the upstream and midstream areas but relatively lower in the downstream area. 36265712 1 84 dep quality 216:222 arg1 the 212:214 the 212:214 the 212:214 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 8 85 theme aromatic 1440:1447 arg1 MW > 35 kDa 1461:1471 MW > 35 kDa 1461:1471 MW > 35 kDa 1461:1471 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 8 85 theme aromatic 1440:1447 arg1 components 1449:1458 aromatic components 1440:1458 aromatic components (MW > 35 kDa) 1440:1472 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 3 86 theme microbial 706:714 arg1 communities 716:726 microbial communities 706:726 microbial communities 706:726 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 1 87 theme dissolved 240:248 arg1 DOM 266:268 DOM 266:268 DOM 266:268 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 1 87 theme dissolved 240:248 arg1 matter 258:263 dissolved organic matter 240:263 dissolved organic matter (DOM) fluxes in rivers 240:286 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 36265712 2 88 from composition 417:427 arg1 rivers 486:491 effluent-dominated rivers 467:491 effluent-dominated rivers 467:491 However, relationships between DOM molecular composition and microbial lifestyle strategies in effluent-dominated rivers are poorly understood. 36265712 8 89 theme Proteobacteria 1518:1531 arg1 degradation 1503:1513 the degradation 1499:1513 the degradation of Proteobacteria and Actinobacteria (K-strategists) 1499:1566 Based on multivariate statistical analysis, the decrease in aromatic components (MW > 35 kDa) was mainly attributed to the degradation of Proteobacteria and Actinobacteria (K-strategists), resulting in a decrease in their relative abundance along the river course. 36265712 3 90 theme DOM 558:560 arg1 structure 562:570 DOM structure 558:570 DOM structure 558:570 Herein, we investigated the variations in DOM structure and composition of an effluent-dominated river and further revealed how these changes alter the abundance and lifestyle strategies of microbial communities. 36265712 1 91 theme matter 258:263 arg1 fluxes 271:276 dissolved organic matter (DOM) fluxes 240:276 dissolved organic matter (DOM) fluxes in rivers 240:286 Urbanization has dramatically changed the quality and quantity of dissolved organic matter (DOM) fluxes in rivers, thereby affecting the diversity and lifestyle strategies of microbial communities. 37065142 10 0 theme environmental 1991:2003 arg1 conversion 2005:2014 environmental conversion 1991:2014 environmental conversion 1991:2014 This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion. 37065142 7 1 theme remodeled 1117:1125 arg1 composition 1138:1148 The remodeled microbiota composition 1113:1148 The remodeled microbiota composition due to exposure in farm A 1113:1174 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 10 2 from patterns 1967:1974 arg1 response 1979:1986 response 1979:1986 response to environmental conversion 1979:2014 This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion. 37065142 6 3 theme different 903:911 arg1 patterns 923:930 compositionally different microbial patterns 887:930 compositionally different microbial patterns 887:930 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 7 4 from exposure 1157:1164 arg1 A 1174:1174 farm A 1169:1174 farm A 1169:1174 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 0 5 from exposure 13:20 arg1 farm 31:34 swine farm 25:34 swine farm 25:34 Occupational exposure in swine farm defines human skin and nasal microbiota. 37065142 7 6 theme microbiota 1127:1136 arg1 composition 1138:1148 The remodeled microbiota composition 1113:1148 The remodeled microbiota composition due to exposure in farm A 1113:1174 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 3 7 from internships 501:511 arg1 farms 522:526 swine farms 516:526 swine farms 516:526 The microbiota of volunteers was longitudinally profiled in a 9-months survey, in which the volunteers underwent occupational exposure during 3-month internships in swine farms. 37065142 2 8 theme microbiome 329:338 arg1 formation 340:348 microbiome formation 329:348 microbiome formation 329:348 Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. 37065142 2 9 from impact 294:299 arg1 formation 340:348 microbiome formation 329:348 microbiome formation 329:348 Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. 37065142 4 10 theme occupational 575:586 arg1 exposure 588:595 occupational exposure 575:595 occupational exposure 575:595 By high-throughput sequencing, we showed that occupational exposure compositionally and functionally reshaped the volunteers' skin and nasal microbiota. 37065142 5 11 theme skin 740:743 arg1 diversity 727:735 the microbial diversity 713:735 the microbial diversity of skin and nasal microbiota 713:764 The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. 37065142 6 12 theme microbial 913:921 arg1 patterns 923:930 compositionally different microbial patterns 887:930 compositionally different microbial patterns 887:930 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 7 13 from volunteers 1233:1242 arg1 B 1252:1252 farm B 1247:1252 farm B 1247:1252 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 6 14 theme Firmicutes 1000:1009 arg1 expense 989:995 expense 989:995 expense of Firmicutes 989:1009 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 8 15 theme metabolic 1359:1367 arg1 pathways 1369:1376 Several metabolic pathways 1351:1376 Several metabolic pathways 1351:1376 Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. 37065142 5 16 from exposure 823:830 arg1 B 840:840 farm B 835:840 farm B 835:840 The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. 37065142 10 17 from dynamics 1945:1952 arg1 response 1979:1986 response 1979:1986 response to environmental conversion 1979:2014 This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion. 37065142 2 18 theme swine 266:270 arg1 farms 272:276 controlled swine farms 255:276 controlled swine farms 255:276 Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. 37065142 10 19 theme microbial 1957:1965 arg1 patterns 1967:1974 microbial patterns 1957:1974 microbial patterns in response to environmental conversion 1957:2014 This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion. 37065142 5 20 theme nasal 749:753 arg1 microbiota 755:764 nasal microbiota 749:764 nasal microbiota 749:764 The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. 37065142 7 21 theme better 1261:1266 arg1 resilience 1268:1277 better resilience 1261:1277 better resilience to revert to the pre-exposure state within 9 months after the exposure 1261:1348 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 9 22 theme different 1754:1762 arg1 farms 1770:1774 different swine farms 1754:1774 different swine farms 1754:1774 We proposed that the differently modified microbiota patterns might be coordinated by microbial and non-microbial factors in different swine farms, which were always environment-specific. 37065142 2 23 theme controlled 255:264 arg1 farms 272:276 controlled swine farms 255:276 controlled swine farms 255:276 Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. 37065142 7 24 theme pre-exposure 1296:1307 arg1 state 1309:1313 the pre-exposure state 1292:1313 the pre-exposure state within 9 months 1292:1329 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 2 25 dep exposure 230:237 arg1 response 214:221 response 214:221 response 214:221 Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. 37065142 5 26 theme microbiota 755:764 arg1 diversity 727:735 the microbial diversity 713:735 the microbial diversity of skin and nasal microbiota 713:764 The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. 37065142 7 27 from B 1252:1252 arg1 microbiota 1219:1228 the microbiota 1215:1228 the microbiota of volunteers in farm B 1215:1252 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 6 28 from exposure 847:854 arg1 farms 869:873 different farms 859:873 different farms 859:873 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 10 29 from response 1979:1986 arg1 dynamics 1945:1952 the dynamics 1941:1952 the dynamics of microbial patterns in response to environmental conversion 1941:2014 This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion. 37065142 3 30 theme volunteers 369:378 arg1 microbiota 355:364 The microbiota 351:364 The microbiota of volunteers 351:378 The microbiota of volunteers was longitudinally profiled in a 9-months survey, in which the volunteers underwent occupational exposure during 3-month internships in swine farms. 37065142 8 31 theme beta-lactam 1533:1543 arg1 resistance 1545:1554 beta-lactam resistance 1533:1554 beta-lactam resistance 1533:1554 Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. 37065142 6 32 from exposure 1017:1024 arg1 A 1034:1034 farm A 1029:1034 farm A 1029:1034 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 7 33 theme farm 1247:1250 arg1 B 1252:1252 farm B 1247:1252 farm B 1247:1252 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 1 34 theme Anthropogenic 77:89 arg1 environments 91:102 Anthropogenic environments 77:102 Anthropogenic environments 77:102 Anthropogenic environments take an active part in shaping the human microbiome. 37065142 3 35 theme 9-months 413:420 arg1 survey 422:427 a 9-months survey 411:427 a 9-months survey 411:427 The microbiota of volunteers was longitudinally profiled in a 9-months survey, in which the volunteers underwent occupational exposure during 3-month internships in swine farms. 37065142 0 36 theme Occupational 0:11 arg1 exposure 13:20 Occupational exposure 0:20 Occupational exposure in swine farm 0:34 Occupational exposure in swine farm defines human skin and nasal microbiota. 37065142 7 37 from microbiota 1219:1228 arg1 B 1252:1252 farm B 1247:1252 farm B 1247:1252 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 8 38 theme Several 1351:1357 arg1 pathways 1369:1376 Several metabolic pathways 1351:1376 Several metabolic pathways 1351:1376 Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. 37065142 0 39 theme swine 25:29 arg1 farm 31:34 swine farm 25:34 swine farm 25:34 Occupational exposure in swine farm defines human skin and nasal microbiota. 37065142 9 40 theme modified 1662:1669 arg1 patterns 1682:1689 the differently modified microbiota patterns 1646:1689 the differently modified microbiota patterns 1646:1689 We proposed that the differently modified microbiota patterns might be coordinated by microbial and non-microbial factors in different swine farms, which were always environment-specific. 37065142 6 41 from predominant 1072:1082 arg1 volunteers 1091:1100 the volunteers 1087:1100 the volunteers in farm B 1087:1110 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 5 42 theme farm 835:838 arg1 B 840:840 farm B 835:840 farm B 835:840 The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. 37065142 7 43 theme farm 1169:1172 arg1 A 1174:1174 farm A 1169:1174 farm A 1169:1174 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 8 44 theme resistance 1545:1554 arg1 function 1521:1528 the function 1517:1528 the function of beta-lactam resistance 1517:1554 Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. 37065142 5 45 theme microbial 717:725 arg1 diversity 727:735 the microbial diversity 713:735 the microbial diversity of skin and nasal microbiota 713:764 The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. 37065142 8 46 theme N-glycan 1424:1431 arg1 biosynthesis 1433:1444 N-glycan biosynthesis 1424:1444 N-glycan biosynthesis 1424:1444 Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. 37065142 7 47 theme volunteers 1233:1242 arg1 microbiota 1219:1228 the microbiota 1215:1228 the microbiota of volunteers in farm B 1215:1252 The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. 37065142 3 48 theme 3-month 493:499 arg1 internships 501:511 3-month internships 493:511 3-month internships in swine farms 493:526 The microbiota of volunteers was longitudinally profiled in a 9-months survey, in which the volunteers underwent occupational exposure during 3-month internships in swine farms. 37065142 8 49 from exposure 1586:1593 arg1 A 1603:1603 farm A 1598:1603 farm A 1598:1603 Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. 37065142 6 50 theme different 859:867 arg1 farms 869:873 different farms 859:873 different farms 859:873 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 4 51 theme nasal 664:668 arg1 microbiota 670:679 nasal microbiota 664:679 nasal microbiota 664:679 By high-throughput sequencing, we showed that occupational exposure compositionally and functionally reshaped the volunteers' skin and nasal microbiota. 37065142 5 52 theme skin 793:796 arg1 microbiota 779:788 the microbiota 775:788 the microbiota of skin and nose 775:805 The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. 37065142 6 53 theme Actinobacteria 953:966 arg1 abundance 940:948 the abundance 936:948 the abundance of Actinobacteria 936:966 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 10 54 theme active 1843:1848 arg1 role 1850:1853 the active role 1839:1853 the active role of occupational exposure in defining the skin and nasal microbiota 1839:1920 This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion. 37065142 8 55 theme farm 1598:1601 arg1 A 1603:1603 farm A 1598:1603 farm A 1598:1603 Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. 37065142 10 56 theme nasal 1905:1909 arg1 microbiota 1911:1920 nasal microbiota 1905:1920 nasal microbiota 1905:1920 This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion. 37065142 5 57 from exposure 686:693 arg1 A 703:703 farm A 698:703 farm A 698:703 The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. 37065142 5 58 theme nose 802:805 arg1 microbiota 779:788 the microbiota 775:788 the microbiota of skin and nose 775:805 The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. 37065142 1 59 theme active 112:117 arg1 part 119:122 an active part 109:122 an active part 109:122 Anthropogenic environments take an active part in shaping the human microbiome. 37065142 0 60 theme human 44:48 arg1 skin 50:53 human skin 44:53 human skin 44:53 Occupational exposure in swine farm defines human skin and nasal microbiota. 37065142 10 61 theme patterns 1967:1974 arg1 dynamics 1945:1952 the dynamics 1941:1952 the dynamics of microbial patterns in response to environmental conversion 1941:2014 This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion. 37065142 5 62 theme farm 698:701 arg1 A 703:703 farm A 698:703 farm A 698:703 The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. 37065142 2 63 theme microbiota 191:200 arg1 dynamics 202:209 skin and nasal microbiota dynamics 176:209 skin and nasal microbiota dynamics 176:209 Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. 37065142 2 64 theme exposure 317:324 arg1 impact 294:299 the impact 290:299 the impact of occupational exposure on microbiome formation 290:348 Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. 37065142 4 65 theme high-throughput 532:546 arg1 sequencing 548:557 high-throughput sequencing 532:557 high-throughput sequencing 532:557 By high-throughput sequencing, we showed that occupational exposure compositionally and functionally reshaped the volunteers' skin and nasal microbiota. 37065142 2 66 theme nasal 185:189 arg1 microbiota 191:200 nasal microbiota 185:200 nasal microbiota 185:200 Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. 37065142 2 67 theme occupational 304:315 arg1 exposure 317:324 occupational exposure 304:324 occupational exposure 304:324 Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. 37065142 8 68 theme farm 1621:1624 arg1 B 1626:1626 farm B 1621:1626 farm B 1621:1626 Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. 37065142 9 69 theme microbial 1715:1723 arg1 factors 1743:1749 microbial and non-microbial factors 1715:1749 microbial and non-microbial factors 1715:1749 We proposed that the differently modified microbiota patterns might be coordinated by microbial and non-microbial factors in different swine farms, which were always environment-specific. 37065142 10 70 theme exposure 1871:1878 arg1 role 1850:1853 the active role 1839:1853 the active role of occupational exposure in defining the skin and nasal microbiota 1839:1920 This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion. 37065142 6 71 theme farm 1105:1108 arg1 B 1110:1110 farm B 1105:1110 farm B 1105:1110 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 3 72 theme occupational 464:475 arg1 exposure 477:484 occupational exposure 464:484 occupational exposure during 3-month internships in swine farms 464:526 The microbiota of volunteers was longitudinally profiled in a 9-months survey, in which the volunteers underwent occupational exposure during 3-month internships in swine farms. 37065142 0 73 theme nasal 59:63 arg1 microbiota 65:74 nasal microbiota 59:74 nasal microbiota 59:74 Occupational exposure in swine farm defines human skin and nasal microbiota. 37065142 2 74 theme skin 176:179 arg1 dynamics 202:209 skin and nasal microbiota dynamics 176:209 skin and nasal microbiota dynamics 176:209 Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. 37065142 6 75 from volunteers 1091:1100 arg1 predominant 1072:1082 predominant 1072:1082 predominant 1072:1082 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 6 75 from volunteers 1091:1100 arg1 B 1110:1110 farm B 1105:1110 farm B 1105:1110 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 3 76 theme swine 516:520 arg1 farms 522:526 swine farms 516:526 swine farms 516:526 The microbiota of volunteers was longitudinally profiled in a 9-months survey, in which the volunteers underwent occupational exposure during 3-month internships in swine farms. 37065142 10 77 theme occupational 1858:1869 arg1 exposure 1871:1878 occupational exposure 1858:1878 occupational exposure 1858:1878 This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion. 37065142 6 78 theme farm 1029:1032 arg1 A 1034:1034 farm A 1029:1034 farm A 1029:1034 The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. 37065142 9 79 theme non-microbial 1729:1741 arg1 factors 1743:1749 microbial and non-microbial factors 1715:1749 microbial and non-microbial factors 1715:1749 We proposed that the differently modified microbiota patterns might be coordinated by microbial and non-microbial factors in different swine farms, which were always environment-specific. 37065142 8 80 theme PICRUSt 1486:1492 arg1 analysis 1494:1501 our PICRUSt analysis 1482:1501 our PICRUSt analysis 1482:1501 Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. 37065142 1 81 theme human 139:143 arg1 microbiome 145:154 the human microbiome 135:154 the human microbiome 135:154 Anthropogenic environments take an active part in shaping the human microbiome. 37065142 9 82 theme microbiota 1671:1680 arg1 patterns 1682:1689 the differently modified microbiota patterns 1646:1689 the differently modified microbiota patterns 1646:1689 We proposed that the differently modified microbiota patterns might be coordinated by microbial and non-microbial factors in different swine farms, which were always environment-specific. 37065142 9 83 theme swine 1764:1768 arg1 farms 1770:1774 different swine farms 1754:1774 different swine farms 1754:1774 We proposed that the differently modified microbiota patterns might be coordinated by microbial and non-microbial factors in different swine farms, which were always environment-specific. 36304083 6 0 theme Lachnospiraceae 1024:1038 arg1 abundance 1040:1048 the Lachnospiraceae abundance 1020:1048 the Lachnospiraceae abundance 1020:1048 The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. 36304083 10 1 theme bacteria 1956:1963 arg1 abundances 1942:1951 the abundances 1938:1951 the abundances of bacteria 1938:1963 CONCLUSION LDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose. 36304083 1 2 theme low-dose 213:220 arg1 LDR 242:244 LDR 242:244 LDR 242:244 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 1 2 theme low-dose 213:220 arg1 radiation 231:239 low-dose ionizing radiation 213:239 low-dose ionizing radiation (LDR) 213:245 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 4 3 from changes 609:615 arg1 levels 654:659 thyroid stimulating hormone (TSH) levels 620:659 thyroid stimulating hormone (TSH) levels in the irradiated mice 620:682 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 1 4 theme radiation 231:239 arg1 effects 202:208 the effects 198:208 the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition 198:302 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 3 5 theme stool 487:491 arg1 samples 493:499 stool samples 487:499 stool samples 487:499 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 1 6 theme health 155:160 arg1 maintenance 134:144 the maintenance 130:144 the maintenance of human health 130:160 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 0 7 theme gut 57:59 arg1 microbiota 61:70 the gut microbiota 53:70 the gut microbiota 53:70 Effect of low-dose radiation on thyroid function and the gut microbiota. 36304083 3 8 theme ribosomal 520:528 arg1 rRNA 535:538 rRNA 535:538 rRNA 535:538 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 3 8 theme ribosomal 520:528 arg1 RNA 530:532 ribosomal RNA 520:532 ribosomal RNA (rRNA) gene sequencing 520:555 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 9 9 dep Encyclopedia 1668:1679 arg1 annotation 1710:1719 pathway annotation 1702:1719 pathway annotation 1702:1719 Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. 36304083 1 10 from effects 202:208 arg1 composition 292:302 gut microbiota composition 277:302 gut microbiota composition 277:302 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 1 10 from effects 202:208 arg1 levels 266:271 thyroid hormone levels 250:271 thyroid hormone levels 250:271 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 10 11 theme CONCLUSION 1856:1865 arg1 LDR 1867:1869 CONCLUSION LDR 1856:1869 CONCLUSION LDR 1856:1869 CONCLUSION LDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose. 36304083 9 12 theme processing 1787:1796 arg1 translation 1819:1829 translation 1819:1829 translation 1819:1829 Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. 36304083 9 12 theme processing 1787:1796 arg1 repair 1848:1853 repair 1848:1853 repair 1848:1853 Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. 36304083 9 12 theme processing 1787:1796 arg1 replication 1832:1842 replication 1832:1842 replication 1832:1842 Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. 36304083 9 12 theme processing 1787:1796 arg1 functions 1798:1806 processing functions 1787:1806 processing functions 1787:1806 Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. 36304083 7 13 theme radiation 1373:1381 arg1 exposure 1383:1390 radiation exposure 1373:1390 radiation exposure 1373:1390 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 5 14 theme LDR-exposed 849:859 arg1 group 861:865 the LDR-exposed group 845:865 the LDR-exposed group 845:865 No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. 36304083 4 15 theme thyroid 620:626 arg1 TSH 649:651 TSH 649:651 TSH 649:651 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 4 15 theme thyroid 620:626 arg1 hormone 640:646 thyroid stimulating hormone 620:646 thyroid stimulating hormone (TSH) levels in the irradiated mice 620:682 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 1 16 theme gut 277:279 arg1 composition 292:302 gut microbiota composition 277:302 gut microbiota composition 277:302 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 10 17 theme thyroid 1882:1888 arg1 function 1890:1897 thyroid function 1882:1897 thyroid function 1882:1897 CONCLUSION LDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose. 36304083 5 18 theme gut 813:815 arg1 microbiota 817:826 the gut microbiota 809:826 the gut microbiota 809:826 No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. 36304083 6 19 theme Enterobacteriaceae 933:950 arg1 abundance 902:910 The abundance 898:910 The abundance of Moraxellaceae and Enterobacteriaceae 898:950 The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. 36304083 8 20 theme functional 1530:1539 arg1 metabolism 1597:1606 carbohydrate metabolism 1584:1606 carbohydrate metabolism 1584:1606 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 8 20 theme functional 1530:1539 arg1 biosynthesis 1620:1631 glycan biosynthesis 1613:1631 glycan biosynthesis 1613:1631 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 8 20 theme functional 1530:1539 arg1 metabolism 1572:1581 nucleotide metabolism 1561:1581 nucleotide metabolism 1561:1581 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 8 20 theme functional 1530:1539 arg1 activities 1541:1550 functional activities 1530:1550 functional activities 1530:1550 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 8 20 theme functional 1530:1539 arg1 metabolism 1637:1646 metabolism 1637:1646 metabolism 1637:1646 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 1 21 dep BACKGROUND 73:82 arg1 has 105:107 has 105:107 has a great influence on the maintenance of human health 105:160 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 6 22 theme Moraxellaceae 915:927 arg1 abundance 902:910 The abundance 898:910 The abundance of Moraxellaceae and Enterobacteriaceae 898:950 The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. 36304083 0 23 from Effect 0:5 arg1 microbiota 61:70 the gut microbiota 53:70 the gut microbiota 53:70 Effect of low-dose radiation on thyroid function and the gut microbiota. 36304083 0 23 from Effect 0:5 arg1 function 40:47 thyroid function 32:47 thyroid function 32:47 Effect of low-dose radiation on thyroid function and the gut microbiota. 36304083 7 24 theme uncultured_bacterium_ 1171:1191 arg1 o_Mollicutes_RF39 1193:1209 uncultured_bacterium_ o_Mollicutes_RF39 1171:1209 uncultured_bacterium_ o_Mollicutes_RF39 1171:1209 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 4 25 theme dose-dependent 698:711 arg1 response 713:720 a dose-dependent response 696:720 a dose-dependent response in thyroid function to ionizing radiation 696:762 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 2 26 theme low-dose 349:356 arg1 radiation 364:372 low-dose X-ray radiation 349:372 low-dose X-ray radiation 349:372 AIM To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice. 36304083 7 27 theme uncultured_bacterium_g_Acinetobacter 1133:1168 arg1 abundances 1119:1128 the abundances 1115:1128 the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus 1115:1286 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 7 28 with correlation 1356:1366 arg1 exposure 1383:1390 radiation exposure 1373:1390 radiation exposure 1373:1390 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 7 28 with correlation 1356:1366 arg1 efficacy 1407:1414 diagnostic efficacy 1396:1414 diagnostic efficacy 1396:1414 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 8 29 theme carbohydrate 1584:1595 arg1 metabolism 1597:1606 carbohydrate metabolism 1584:1606 carbohydrate metabolism 1584:1606 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 2 30 theme male 377:380 arg1 mice 391:394 male C57BL/6J mice 377:394 male C57BL/6J mice 377:394 AIM To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice. 36304083 0 31 theme low-dose 10:17 arg1 radiation 19:27 low-dose radiation 10:27 low-dose radiation 10:27 Effect of low-dose radiation on thyroid function and the gut microbiota. 36304083 2 32 theme radiation 364:372 arg1 effects 338:344 the potential effects 324:344 the potential effects of low-dose X-ray radiation to male C57BL/6J mice 324:394 AIM To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice. 36304083 4 33 theme ionizing 745:752 arg1 radiation 754:762 ionizing radiation 745:762 ionizing radiation 745:762 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 3 34 theme Peripheral 405:414 arg1 blood 416:420 METHODS Peripheral blood 397:420 METHODS Peripheral blood 397:420 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 1 35 theme thyroid 250:256 arg1 levels 266:271 thyroid hormone levels 250:271 thyroid hormone levels 250:271 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 6 36 theme LDR-exposed 969:979 arg1 groups 981:986 the LDR-exposed groups 965:986 the LDR-exposed groups 965:986 The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. 36304083 8 37 theme glycan 1613:1618 arg1 biosynthesis 1620:1631 glycan biosynthesis 1613:1631 glycan biosynthesis 1613:1631 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 10 38 theme gut 1907:1909 arg1 microbiota 1911:1920 the gut microbiota 1903:1920 the gut microbiota 1903:1920 CONCLUSION LDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose. 36304083 8 39 theme metabolic 1440:1448 arg1 pathways 1450:1457 functional metabolic pathways 1429:1457 functional metabolic pathways 1429:1457 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 3 40 theme immunosorbent 454:466 arg1 ELISA 475:479 ELISA 475:479 ELISA 475:479 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 3 40 theme immunosorbent 454:466 arg1 assay 468:472 enzyme-linked immunosorbent assay 440:472 enzyme-linked immunosorbent assay (ELISA) 440:480 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 6 41 theme dose-dependent 1065:1078 arg1 manner 1080:1085 a dose-dependent manner 1063:1085 a dose-dependent manner 1063:1085 The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. 36304083 8 42 contain have 1512:1515 arg1 metabolism 1484:1493 biological metabolism 1473:1493 biological metabolism 1473:1493 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 8 42 contain have 1512:1515 arg2 effect 1520:1525 an effect 1517:1525 an effect 1517:1525 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 8 43 theme biological 1473:1482 arg1 metabolism 1484:1493 biological metabolism 1473:1493 biological metabolism 1473:1493 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 5 44 located observed 833:840 arg1 comparison 870:879 comparison 870:879 comparison to the controls 870:895 No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. 36304083 5 44 located observed 833:840 arg1 group 861:865 the LDR-exposed group 845:865 the LDR-exposed group 845:865 No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. 36304083 5 44 located observed 833:840 arg2 changes 768:774 No changes 765:774 No changes in the diversity and richness of the gut microbiota 765:826 No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. 36304083 9 45 theme pathway 1702:1708 arg1 annotation 1710:1719 pathway annotation 1702:1719 pathway annotation 1702:1719 Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. 36304083 7 46 theme uncultured_ 1252:1262 arg1 bacterium_g_Lactococcus 1264:1286 uncultured_ bacterium_g_Lactococcus 1252:1286 uncultured_ bacterium_g_Lactococcus 1252:1286 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 1 47 contain has 105:107 arg2 influence 117:125 a great influence 109:125 a great influence 109:125 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 1 47 contain has 105:107 arg1 axis 100:103 The thyroid-gut axis 84:103 The thyroid-gut axis 84:103 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 5 48 dep diversity 783:791 arg1 the 779:781 the 779:781 the 779:781 No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. 36304083 1 49 theme ionizing 222:229 arg1 LDR 242:244 LDR 242:244 LDR 242:244 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 1 49 theme ionizing 222:229 arg1 radiation 231:239 low-dose ionizing radiation 213:239 low-dose ionizing radiation (LDR) 213:245 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 10 50 from changes 1927:1933 arg1 abundances 1942:1951 the abundances 1938:1951 the abundances of bacteria 1938:1963 CONCLUSION LDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose. 36304083 4 51 theme hormone 640:646 arg1 levels 654:659 thyroid stimulating hormone (TSH) levels 620:659 thyroid stimulating hormone (TSH) levels in the irradiated mice 620:682 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 10 52 theme radiation 1989:1997 arg1 dose 1999:2002 the radiation dose 1985:2002 the radiation dose 1985:2002 CONCLUSION LDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose. 36304083 1 53 theme human 149:153 arg1 health 155:160 human health 149:160 human health 149:160 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 9 54 from changes 1741:1747 arg1 microbiota 1760:1769 the gut microbiota 1752:1769 the gut microbiota 1752:1769 Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. 36304083 6 55 theme radiated 1094:1101 arg1 groups 1103:1108 the radiated groups 1090:1108 the radiated groups 1090:1108 The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. 36304083 9 56 theme gut 1756:1758 arg1 microbiota 1760:1769 the gut microbiota 1752:1769 the gut microbiota 1752:1769 Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. 36304083 3 57 theme RNA 530:532 arg1 sequencing 546:555 ribosomal RNA (rRNA) gene sequencing 520:555 ribosomal RNA (rRNA) gene sequencing 520:555 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 3 58 link enzyme-linked 440:452 arg1 ELISA 475:479 ELISA 475:479 ELISA 475:479 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 3 58 link enzyme-linked 440:452 arg1 assay 468:472 enzyme-linked immunosorbent assay 440:472 enzyme-linked immunosorbent assay (ELISA) 440:480 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 7 59 theme diagnostic 1396:1405 arg1 efficacy 1407:1414 diagnostic efficacy 1396:1414 diagnostic efficacy 1396:1414 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 5 60 from changes 768:774 arg1 richness 797:804 richness 797:804 richness 797:804 No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. 36304083 5 60 from changes 768:774 arg1 diversity 783:791 diversity 783:791 diversity 783:791 No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. 36304083 1 61 theme great 111:115 arg1 influence 117:125 a great influence 109:125 a great influence 109:125 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 7 62 theme uncultured_bacterium_g_Citrobacter 1212:1245 arg1 abundances 1119:1128 the abundances 1115:1128 the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus 1115:1286 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 3 63 theme gene 541:544 arg1 sequencing 546:555 ribosomal RNA (rRNA) gene sequencing 520:555 ribosomal RNA (rRNA) gene sequencing 520:555 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 7 64 theme o_Mollicutes_RF39 1193:1209 arg1 abundances 1119:1128 the abundances 1115:1128 the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus 1115:1286 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 1 65 theme microbiota 281:290 arg1 composition 292:302 gut microbiota composition 277:302 gut microbiota composition 277:302 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 4 66 from response 713:720 arg1 function 733:740 thyroid function 725:740 thyroid function 725:740 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 5 67 theme microbiota 817:826 arg1 richness 797:804 richness 797:804 richness 797:804 No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. 36304083 5 67 theme microbiota 817:826 arg1 diversity 783:791 diversity 783:791 diversity 783:791 No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. 36304083 4 68 theme stimulating 628:638 arg1 TSH 649:651 TSH 649:651 TSH 649:651 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 4 68 theme stimulating 628:638 arg1 hormone 640:646 thyroid stimulating hormone 620:646 thyroid stimulating hormone (TSH) levels in the irradiated mice 620:682 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 8 69 theme nucleotide 1561:1570 arg1 metabolism 1572:1581 nucleotide metabolism 1561:1581 nucleotide metabolism 1561:1581 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 3 70 theme METHODS 397:403 arg1 blood 416:420 METHODS Peripheral blood 397:420 METHODS Peripheral blood 397:420 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 2 71 theme potential 328:336 arg1 effects 338:344 the potential effects 324:344 the potential effects of low-dose X-ray radiation to male C57BL/6J mice 324:394 AIM To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice. 36304083 0 72 theme radiation 19:27 arg1 Effect 0:5 Effect 0:5 Effect of low-dose radiation on thyroid function and the gut microbiota. 0:71 Effect of low-dose radiation on thyroid function and the gut microbiota. 36304083 1 73 theme thyroid-gut 88:98 arg1 axis 100:103 The thyroid-gut axis 84:103 The thyroid-gut axis 84:103 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 7 74 theme genus 1328:1332 arg1 level 1334:1338 the genus level 1324:1338 the genus level 1324:1338 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 2 75 theme C57BL/6J 382:389 arg1 mice 391:394 male C57BL/6J mice 377:394 male C57BL/6J mice 377:394 AIM To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice. 36304083 4 76 theme irradiated 668:677 arg1 mice 679:682 the irradiated mice 664:682 the irradiated mice 664:682 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 0 77 theme thyroid 32:38 arg1 function 40:47 thyroid function 32:47 thyroid function 32:47 Effect of low-dose radiation on thyroid function and the gut microbiota. 36304083 2 78 theme X-ray 358:362 arg1 radiation 364:372 low-dose X-ray radiation 349:372 low-dose X-ray radiation 349:372 AIM To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice. 36304083 1 79 theme hormone 258:264 arg1 levels 266:271 thyroid hormone levels 250:271 thyroid hormone levels 250:271 BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. 36304083 4 80 dep RESULTS 576:582 arg1 found 587:591 found 587:591 found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation 587:762 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 7 81 theme radiated 1305:1312 arg1 groups 1314:1319 the radiated groups 1301:1319 the radiated groups 1301:1319 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 8 82 theme functional 1429:1438 arg1 pathways 1450:1457 functional metabolic pathways 1429:1457 functional metabolic pathways 1429:1457 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 4 83 from levels 654:659 arg1 mice 679:682 the irradiated mice 664:682 the irradiated mice 664:682 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36304083 8 84 theme pathways 1450:1457 arg1 Analysis 1417:1424 Analysis 1417:1424 Analysis of functional metabolic pathways 1417:1457 Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. 36304083 3 85 theme enzyme-linked 440:452 arg1 ELISA 475:479 ELISA 475:479 ELISA 475:479 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 3 85 theme enzyme-linked 440:452 arg1 assay 468:472 enzyme-linked immunosorbent assay 440:472 enzyme-linked immunosorbent assay (ELISA) 440:480 METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. 36304083 9 86 theme Genes 1684:1688 arg1 Genomes 1694:1700 Genomes 1694:1700 Genomes 1694:1700 Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. 36304083 7 87 theme bacterium_g_Lactococcus 1264:1286 arg1 abundances 1119:1128 the abundances 1115:1128 the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus 1115:1286 And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. 36304083 4 88 theme thyroid 725:731 arg1 function 733:740 thyroid function 725:740 thyroid function 725:740 RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. 36369961 8 0 theme respective 1429:1438 arg1 impact 1440:1445 the respective impact 1425:1445 the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved 1425:1573 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 8 1 theme microvinification 1381:1397 arg1 experiments 1399:1409 microvinification experiments 1381:1409 microvinification experiments 1381:1409 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 5 2 from concentration 834:846 arg1 solution 871:878 the solution 867:878 the solution 867:878 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 8 3 dep CONCLUSION 1304:1313 arg1 reflect 1339:1345 reflect 1339:1345 reflect relatively well extraction during microvinification experiments 1339:1409 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 8 3 dep CONCLUSION 1304:1313 arg1 extraction 1363:1372 extraction 1363:1372 extraction 1363:1372 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 8 3 dep CONCLUSION 1304:1313 arg1 highlight 1415:1423 highlight 1415:1423 highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved 1415:1573 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 5 4 theme adsorption 930:939 arg1 effect 920:925 a combined effect 909:925 a combined effect of adsorption and/or precipitation and/or chemical reactions 909:986 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 0 5 theme flesh 81:85 arg1 role 73:76 role 73:76 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 0:96 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 36369961 5 6 theme anthocyanins 816:827 arg1 walls 788:792 cell walls 783:792 cell walls of skin/flesh, and/or anthocyanins 783:827 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 7 7 with systems 1215:1221 arg1 seeds 1236:1240 seeds 1236:1240 seeds 1236:1240 Polyphenol amounts extracted in model systems with skins + seeds + pulp were close to what was extracted in microvinification. 36369961 7 7 with systems 1215:1221 arg1 skins 1228:1232 skins 1228:1232 skins 1228:1232 Polyphenol amounts extracted in model systems with skins + seeds + pulp were close to what was extracted in microvinification. 36369961 0 8 from maceration 47:56 arg1 winemaking 61:70 winemaking 61:70 winemaking 61:70 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 36369961 3 9 dep compartments 593:604 arg1 skins 621:625 skins 621:625 skins 621:625 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 3 9 dep compartments 593:604 arg1 seeds 629:633 seeds 629:633 seeds 629:633 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 3 9 dep compartments 593:604 arg1 skins 607:611 skins 607:611 skins 607:611 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 3 9 dep compartments 593:604 arg1 seeds 614:618 seeds 614:618 seeds 614:618 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 3 9 dep compartments 593:604 arg1 skins 636:640 skins 636:640 skins 636:640 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 3 9 dep compartments 593:604 arg1 seeds 644:648 seeds 644:648 seeds 644:648 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 0 10 theme seeds 91:95 arg1 role 73:76 role 73:76 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 0:96 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 36369961 5 11 theme precipitation 948:960 arg1 effect 920:925 a combined effect 909:925 a combined effect of adsorption and/or precipitation and/or chemical reactions 909:986 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 5 12 theme cell 783:786 arg1 walls 788:792 cell walls 783:792 cell walls of skin/flesh, and/or anthocyanins 783:827 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 1 13 theme phenolic 145:152 arg1 compounds 154:162 phenolic compounds 145:162 phenolic compounds 145:162 BACKGROUND During red winemaking, diffusion of phenolic compounds from the grape berry cells into the liquid phase occurs simultaneously with the adsorption of the same compounds onto the pulp. 36369961 4 14 theme high 715:718 arg1 polyphenols 730:740 polyphenols 730:740 polyphenols 730:740 RESULTS Interestingly, the seeds alone released a rather high amount of polyphenols. 36369961 4 14 theme high 715:718 arg1 amount 720:725 a rather high amount 706:725 a rather high amount of polyphenols 706:740 RESULTS Interestingly, the seeds alone released a rather high amount of polyphenols. 36369961 1 15 dep BACKGROUND 98:107 arg1 occurs 213:218 occurs 213:218 occurs simultaneously with the adsorption of the same compounds onto the pulp 213:289 BACKGROUND During red winemaking, diffusion of phenolic compounds from the grape berry cells into the liquid phase occurs simultaneously with the adsorption of the same compounds onto the pulp. 36369961 3 16 from macerations 538:548 arg1 medium 561:566 a model medium 553:566 a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp 553:655 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 1 17 theme compounds 154:162 arg1 diffusion 132:140 diffusion 132:140 diffusion of phenolic compounds from the grape berry cells into the liquid phase 132:211 BACKGROUND During red winemaking, diffusion of phenolic compounds from the grape berry cells into the liquid phase occurs simultaneously with the adsorption of the same compounds onto the pulp. 36369961 5 18 theme chemical 969:976 arg1 reactions 978:986 chemical reactions 969:986 chemical reactions 969:986 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 4 19 theme polyphenols 730:740 arg1 polyphenols 730:740 polyphenols 730:740 polyphenols 730:740 RESULTS Interestingly, the seeds alone released a rather high amount of polyphenols. 36369961 4 19 theme polyphenols 730:740 arg1 amount 720:725 a rather high amount 706:725 a rather high amount of polyphenols 706:740 RESULTS Interestingly, the seeds alone released a rather high amount of polyphenols. 36369961 2 20 theme polyphenols 346:356 arg1 proportions 331:341 the proportions 327:341 the proportions of polyphenols diffusing from the skins 327:381 In previous studies, we quantified the proportions of polyphenols diffusing from the skins and then assessed the amounts that can be fixed by the pulp. 36369961 8 21 from impact 1440:1445 arg1 composition 1520:1530 the wine's final phenolic composition 1494:1530 the wine's final phenolic composition as well as some of the mechanisms involved 1494:1573 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 8 21 from impact 1440:1445 arg1 some 1543:1546 some 1543:1546 some 1543:1546 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 8 21 from impact 1440:1445 arg1 mechanisms 1555:1564 the mechanisms 1551:1564 the mechanisms involved 1551:1573 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 3 22 theme present 493:499 arg1 seeds 481:485 seeds 481:485 seeds 481:485 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 0 23 theme compounds 22:30 arg1 Diffusion 0:8 Diffusion 0:8 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 0:96 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 36369961 7 24 theme Polyphenol 1177:1186 arg1 amounts 1188:1194 Polyphenol amounts 1177:1194 Polyphenol amounts extracted in model systems with skins + seeds + pulp 1177:1247 Polyphenol amounts extracted in model systems with skins + seeds + pulp were close to what was extracted in microvinification. 36369961 5 25 theme walls 788:792 arg1 presence 771:778 the presence 767:778 the presence of cell walls of skin/flesh, and/or anthocyanins 767:827 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 3 26 theme seeds 481:485 arg1 impact 471:476 the impact 467:476 the impact of seeds, also present during vinification, 467:520 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 1 27 theme grape 173:177 arg1 cells 185:189 the grape berry cells 169:189 the grape berry cells 169:189 BACKGROUND During red winemaking, diffusion of phenolic compounds from the grape berry cells into the liquid phase occurs simultaneously with the adsorption of the same compounds onto the pulp. 36369961 0 28 theme phenolic 13:20 arg1 compounds 22:30 phenolic compounds 13:30 phenolic compounds 13:30 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 36369961 1 29 theme same 262:265 arg1 compounds 267:275 the same compounds 258:275 the same compounds 258:275 BACKGROUND During red winemaking, diffusion of phenolic compounds from the grape berry cells into the liquid phase occurs simultaneously with the adsorption of the same compounds onto the pulp. 36369961 5 30 theme skin/flesh 797:806 arg1 walls 788:792 cell walls 783:792 cell walls of skin/flesh, and/or anthocyanins 783:827 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 5 31 theme combined 911:918 arg1 effect 920:925 a combined effect 909:925 a combined effect of adsorption and/or precipitation and/or chemical reactions 909:986 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 3 32 with medium 561:566 arg1 compartments 593:604 the following berry compartments 573:604 the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp 573:655 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 1 33 theme berry 179:183 arg1 cells 185:189 the grape berry cells 169:189 the grape berry cells 169:189 BACKGROUND During red winemaking, diffusion of phenolic compounds from the grape berry cells into the liquid phase occurs simultaneously with the adsorption of the same compounds onto the pulp. 36369961 1 34 theme compounds 267:275 arg1 adsorption 244:253 the adsorption 240:253 the adsorption of the same compounds onto the pulp 240:289 BACKGROUND During red winemaking, diffusion of phenolic compounds from the grape berry cells into the liquid phase occurs simultaneously with the adsorption of the same compounds onto the pulp. 36369961 1 35 from cells 185:189 arg1 diffusion 132:140 diffusion 132:140 diffusion of phenolic compounds from the grape berry cells into the liquid phase 132:211 BACKGROUND During red winemaking, diffusion of phenolic compounds from the grape berry cells into the liquid phase occurs simultaneously with the adsorption of the same compounds onto the pulp. 36369961 3 36 theme model 555:559 arg1 medium 561:566 a model medium 553:566 a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp 553:655 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 7 37 theme model 1209:1213 arg1 systems 1215:1221 model systems 1209:1221 model systems with skins + seeds + pulp 1209:1247 Polyphenol amounts extracted in model systems with skins + seeds + pulp were close to what was extracted in microvinification. 36369961 0 38 theme model 41:45 arg1 maceration 47:56 a model maceration 39:56 a model maceration in winemaking 39:70 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 36369961 8 39 theme grape 1454:1458 arg1 compartments 1478:1489 the grape berry's different compartments 1450:1489 the grape berry's different compartments 1450:1489 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 3 40 theme berry 587:591 arg1 compartments 593:604 the following berry compartments 573:604 the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp 573:655 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 6 41 theme more 1101:1104 arg1 tannins 1106:1112 more tannins 1101:1112 more tannins 1101:1112 The pulp certainly adsorbed tannins, but they also tended to shift the extraction equilibria, and it seems that more tannins could be extracted from skins and seeds when pulp was present. 36369961 8 42 theme phenolic 1511:1518 arg1 composition 1520:1530 the wine's final phenolic composition 1494:1530 the wine's final phenolic composition as well as some of the mechanisms involved 1494:1573 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 6 43 theme extraction 1060:1069 arg1 equilibria 1071:1080 the extraction equilibria 1056:1080 the extraction equilibria 1056:1080 The pulp certainly adsorbed tannins, but they also tended to shift the extraction equilibria, and it seems that more tannins could be extracted from skins and seeds when pulp was present. 36369961 2 44 theme previous 295:302 arg1 studies 304:310 previous studies 295:310 previous studies 295:310 In previous studies, we quantified the proportions of polyphenols diffusing from the skins and then assessed the amounts that can be fixed by the pulp. 36369961 6 45 theme adsorbed 1008:1015 arg1 tannins 1017:1023 adsorbed tannins 1008:1023 adsorbed tannins 1008:1023 The pulp certainly adsorbed tannins, but they also tended to shift the extraction equilibria, and it seems that more tannins could be extracted from skins and seeds when pulp was present. 36369961 8 46 theme model 1321:1325 arg1 experiments 1327:1337 These model experiments 1315:1337 These model experiments 1315:1337 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 5 47 theme seed 851:854 arg1 tannins 856:862 seed tannins 851:862 seed tannins 851:862 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 1 48 theme red 116:118 arg1 winemaking 120:129 red winemaking 116:129 red winemaking 116:129 BACKGROUND During red winemaking, diffusion of phenolic compounds from the grape berry cells into the liquid phase occurs simultaneously with the adsorption of the same compounds onto the pulp. 36369961 1 49 theme liquid 200:205 arg1 phase 207:211 the liquid phase 196:211 the liquid phase 196:211 BACKGROUND During red winemaking, diffusion of phenolic compounds from the grape berry cells into the liquid phase occurs simultaneously with the adsorption of the same compounds onto the pulp. 36369961 9 50 theme Chemical 1594:1601 arg1 Industry 1603:1610 Chemical Industry 1594:1610 Chemical Industry 1594:1610 © 2022 Society of Chemical Industry. 36369961 3 51 theme following 577:585 arg1 compartments 593:604 the following berry compartments 573:604 the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp 573:655 In this work, we added the impact of seeds, also present during vinification, by carrying out macerations in a model medium with the following berry compartments: skins, seeds, skins + seeds, skins + seeds + pulp. 36369961 5 52 theme tannins 856:862 arg1 concentration 834:846 the concentration 830:846 the concentration of seed tannins in the solution 830:878 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 8 53 theme final 1505:1509 arg1 composition 1520:1530 the wine's final phenolic composition 1494:1530 the wine's final phenolic composition as well as some of the mechanisms involved 1494:1573 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 36369961 5 54 theme reactions 978:986 arg1 effect 920:925 a combined effect 909:925 a combined effect of adsorption and/or precipitation and/or chemical reactions 909:986 As soon as they were in the presence of cell walls of skin/flesh, and/or anthocyanins, the concentration of seed tannins in the solution dropped dramatically, due to a combined effect of adsorption and/or precipitation and/or chemical reactions. 36369961 0 55 dep Diffusion 0:8 arg1 role 73:76 role 73:76 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 0:96 Diffusion of phenolic compounds during a model maceration in winemaking: role of flesh and seeds. 36369961 8 56 theme different 1468:1476 arg1 compartments 1478:1489 the grape berry's different compartments 1450:1489 the grape berry's different compartments 1450:1489 CONCLUSION These model experiments reflect relatively well extraction during microvinification experiments and highlight the respective impact of the grape berry's different compartments in the wine's final phenolic composition as well as some of the mechanisms involved. 37107373 0 0 theme Polysaccharide 87:100 arg1 Effect 55:60 the Effect 51:60 the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity 51:121 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 37107373 5 1 theme lipid 703:707 arg1 levels 709:714 The obesity and serum lipid levels 681:714 levels 709:714 The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. 37107373 9 2 theme acid 1436:1439 arg1 metabolism 1441:1450 amino acid metabolism 1430:1450 amino acid metabolism 1430:1450 The function of gut microbiota mainly regulated lipid metabolism and amino acid metabolism. 37107373 12 3 used used 1887:1890 arg2 SRP 1874:1876 SRP 1874:1876 SRP 1874:1876 The study results suggest that SRP significantly alleviated obesity via gut-microbiota-related metabolic pathways, and SRP could be used for the prevention and treatment of obesity. 37107373 11 4 theme phenylalanine 1660:1672 arg1 pathway 1685:1691 the phenylalanine metabolism pathway 1656:1691 the phenylalanine metabolism pathway 1656:1691 Furthermore, linoleic acid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and the phenylalanine metabolism pathway played a role in improving obesity in those treated with SRP. 37107373 0 5 theme reilianum 77:85 arg1 Polysaccharide 87:100 Sporisorium reilianum Polysaccharide 65:100 Sporisorium reilianum Polysaccharide 65:100 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 37107373 12 6 theme metabolic 1850:1858 arg1 pathways 1860:1867 gut-microbiota-related metabolic pathways 1827:1867 gut-microbiota-related metabolic pathways 1827:1867 The study results suggest that SRP significantly alleviated obesity via gut-microbiota-related metabolic pathways, and SRP could be used for the prevention and treatment of obesity. 37107373 4 7 theme microbiota 632:641 arg1 index 610:614 the related index 598:614 the related index of obesity, gut microbiota, and untargeted metabolomics of rats 598:678 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 12 8 theme obesity 1928:1934 arg1 prevention 1900:1909 prevention 1900:1909 prevention 1900:1909 The study results suggest that SRP significantly alleviated obesity via gut-microbiota-related metabolic pathways, and SRP could be used for the prevention and treatment of obesity. 37107373 12 8 theme obesity 1928:1934 arg1 treatment 1915:1923 treatment 1915:1923 treatment 1915:1923 The study results suggest that SRP significantly alleviated obesity via gut-microbiota-related metabolic pathways, and SRP could be used for the prevention and treatment of obesity. 37107373 6 9 dep composition 900:910 arg1 the 896:898 the 896:898 the 896:898 SRP improved the composition and function of gut microbiota in rats fed with a high-fat diet, and decreased the ratio of Firmicutes to Bacteroides at the phylum level. 37107373 8 10 theme helveticus 1225:1234 arg1 abundance 1173:1181 the abundance 1169:1181 the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus 1169:1265 At the species level, the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus increased, while the abundance of Lactobacillus reuteri and Staphylococcus xylosus decreased. 37107373 6 11 theme phylum 1037:1042 arg1 level 1044:1048 the phylum level 1033:1048 the phylum level 1033:1048 SRP improved the composition and function of gut microbiota in rats fed with a high-fat diet, and decreased the ratio of Firmicutes to Bacteroides at the phylum level. 37107373 8 12 theme Lactobacillus 1211:1223 arg1 helveticus 1225:1234 Lactobacillus helveticus 1211:1234 Lactobacillus helveticus 1211:1234 At the species level, the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus increased, while the abundance of Lactobacillus reuteri and Staphylococcus xylosus decreased. 37107373 5 13 theme SRP 878:880 arg1 dose 870:873 a high dose 863:873 a high dose of SRP 863:880 The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. 37107373 11 14 theme linoleic 1572:1579 arg1 metabolism 1586:1595 linoleic acid metabolism 1572:1595 linoleic acid metabolism 1572:1595 Furthermore, linoleic acid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and the phenylalanine metabolism pathway played a role in improving obesity in those treated with SRP. 37107373 4 15 theme untargeted 648:657 arg1 metabolomics 659:670 untargeted metabolomics 648:670 untargeted metabolomics of rats 648:678 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 5 16 theme lipid 759:763 arg1 accumulation 765:776 lipid accumulation 759:776 lipid accumulation in the liver and adipocyte hypertrophy 759:815 The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. 37107373 10 17 theme untargeted 1457:1466 arg1 metabolomics 1468:1479 The untargeted metabolomics 1453:1479 The untargeted metabolomics 1453:1479 The untargeted metabolomics indicated that 36 metabolites were related to the anti-obesity effect of SRP. 37107373 4 18 theme obesity 619:625 arg1 index 610:614 the related index 598:614 the related index of obesity, gut microbiota, and untargeted metabolomics of rats 598:678 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 12 19 dep prevention 1900:1909 arg1 the 1896:1898 the 1896:1898 the 1896:1898 The study results suggest that SRP significantly alleviated obesity via gut-microbiota-related metabolic pathways, and SRP could be used for the prevention and treatment of obesity. 37107373 3 20 from obesity 401:407 arg1 rats 437:440 male Sprague Dawley (SD) rats 412:440 male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) 412:471 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 10 21 theme SRP 1554:1556 arg1 effect 1544:1549 the anti-obesity effect 1527:1549 the anti-obesity effect of SRP 1527:1556 The untargeted metabolomics indicated that 36 metabolites were related to the anti-obesity effect of SRP. 37107373 7 22 theme genus 1058:1062 arg1 level 1064:1068 the genus level 1054:1068 the genus level 1054:1068 At the genus level, the abundance of Lactobacillus increased and that of Bacteroides decreased. 37107373 4 23 theme related 602:608 arg1 index 610:614 the related index 598:614 the related index of obesity, gut microbiota, and untargeted metabolomics of rats 598:678 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 12 24 theme study 1759:1763 arg1 results 1765:1771 The study results 1755:1771 The study results 1755:1771 The study results suggest that SRP significantly alleviated obesity via gut-microbiota-related metabolic pathways, and SRP could be used for the prevention and treatment of obesity. 37107373 3 25 theme polysaccharides 341:355 arg1 mechanism 328:336 the potential mechanism 314:336 the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) 314:471 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 7 26 theme Lactobacillus 1088:1100 arg1 abundance 1075:1083 the abundance 1071:1083 the abundance of Lactobacillus 1071:1100 At the genus level, the abundance of Lactobacillus increased and that of Bacteroides decreased. 37107373 8 27 theme acidophilus 1255:1265 arg1 abundance 1173:1181 the abundance 1169:1181 the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus 1169:1265 At the species level, the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus increased, while the abundance of Lactobacillus reuteri and Staphylococcus xylosus decreased. 37107373 11 28 theme phenylalanine 1598:1610 arg1 biosynthesis 1638:1649 phenylalanine, tyrosine, and tryptophan biosynthesis 1598:1649 phenylalanine, tyrosine, and tryptophan biosynthesis 1598:1649 Furthermore, linoleic acid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and the phenylalanine metabolism pathway played a role in improving obesity in those treated with SRP. 37107373 1 29 theme obesity 189:195 arg1 pathophysiology 170:184 the pathophysiology 166:184 the pathophysiology of obesity 166:195 Gut microbiota plays an important role in the pathophysiology of obesity. 37107373 0 30 theme Metagenomic 0:10 arg1 Analysis 39:46 Metagenomic and Untargeted Metabolomic Analysis 0:46 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 0:122 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 37107373 4 31 theme SRP 538:540 arg1 mg/kg/day 561:569 100, 200, and 400 mg/kg/day 543:569 100, 200, and 400 mg/kg/day 543:569 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 4 31 theme SRP 538:540 arg1 weeks 529:533 8 weeks 527:533 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention 527:583 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 12 32 theme gut-microbiota-related 1827:1848 arg1 pathways 1860:1867 gut-microbiota-related metabolic pathways 1827:1867 gut-microbiota-related metabolic pathways 1827:1867 The study results suggest that SRP significantly alleviated obesity via gut-microbiota-related metabolic pathways, and SRP could be used for the prevention and treatment of obesity. 37107373 4 33 theme rats 675:678 arg1 microbiota 632:641 gut microbiota 628:641 gut microbiota 628:641 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 4 33 theme rats 675:678 arg1 metabolomics 659:670 untargeted metabolomics 648:670 untargeted metabolomics of rats 648:678 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 4 33 theme rats 675:678 arg1 obesity 619:625 obesity 619:625 obesity 619:625 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 5 34 theme adipocyte 795:803 arg1 hypertrophy 805:815 adipocyte hypertrophy 795:815 adipocyte hypertrophy 795:815 The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. 37107373 0 35 theme Metabolomic 27:37 arg1 Analysis 39:46 Metagenomic and Untargeted Metabolomic Analysis 0:46 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 0:122 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 37107373 5 36 theme high 865:868 arg1 dose 870:873 a high dose 863:873 a high dose of SRP 863:880 The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. 37107373 3 37 theme high-fat 453:460 arg1 HFD 468:470 HFD 468:470 HFD 468:470 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 3 37 theme high-fat 453:460 arg1 diet 462:465 a high-fat diet 451:465 a high-fat diet (HFD) 451:471 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 0 38 theme Untargeted 16:25 arg1 Analysis 39:46 Metagenomic and Untargeted Metabolomic Analysis 0:46 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 0:122 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 37107373 9 39 theme lipid 1409:1413 arg1 metabolism 1415:1424 lipid metabolism 1409:1424 lipid metabolism 1409:1424 The function of gut microbiota mainly regulated lipid metabolism and amino acid metabolism. 37107373 3 40 from reilianum 374:382 arg1 polysaccharides 341:355 polysaccharides 341:355 polysaccharides from Sporisorium reilianum (SRP) 341:388 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 3 40 from reilianum 374:382 arg1 mechanism 328:336 the potential mechanism 314:336 the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) 314:471 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 8 41 theme crispatus 1200:1208 arg1 abundance 1173:1181 the abundance 1169:1181 the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus 1169:1265 At the species level, the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus increased, while the abundance of Lactobacillus reuteri and Staphylococcus xylosus decreased. 37107373 1 42 theme important 148:156 arg1 role 158:161 an important role 145:161 an important role 145:161 Gut microbiota plays an important role in the pathophysiology of obesity. 37107373 3 43 theme Dawley 425:430 arg1 rats 437:440 male Sprague Dawley (SD) rats 412:440 male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) 412:471 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 8 44 theme xylosus 1342:1348 arg1 abundance 1288:1296 the abundance 1284:1296 the abundance of Lactobacillus reuteri and Staphylococcus xylosus 1284:1348 At the species level, the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus increased, while the abundance of Lactobacillus reuteri and Staphylococcus xylosus decreased. 37107373 8 45 theme species 1154:1160 arg1 level 1162:1166 the species level 1150:1166 the species level 1150:1166 At the species level, the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus increased, while the abundance of Lactobacillus reuteri and Staphylococcus xylosus decreased. 37107373 4 46 theme gut 628:630 arg1 microbiota 632:641 gut microbiota 628:641 gut microbiota 628:641 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 5 47 theme rats 719:722 arg1 obesity 685:691 The obesity and serum lipid levels 681:714 obesity 685:691 The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. 37107373 5 47 theme rats 719:722 arg1 levels 709:714 The obesity and serum lipid levels 681:714 levels 709:714 The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. 37107373 9 48 theme microbiota 1381:1390 arg1 function 1365:1372 The function 1361:1372 The function of gut microbiota 1361:1390 The function of gut microbiota mainly regulated lipid metabolism and amino acid metabolism. 37107373 5 49 from accumulation 765:776 arg1 liver 785:789 liver 785:789 liver 785:789 The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. 37107373 5 49 from accumulation 765:776 arg1 hypertrophy 805:815 adipocyte hypertrophy 795:815 adipocyte hypertrophy 795:815 The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. 37107373 6 50 theme high-fat 962:969 arg1 diet 971:974 a high-fat diet 960:974 a high-fat diet 960:974 SRP improved the composition and function of gut microbiota in rats fed with a high-fat diet, and decreased the ratio of Firmicutes to Bacteroides at the phylum level. 37107373 0 51 theme Effect 55:60 arg1 Analysis 39:46 Metagenomic and Untargeted Metabolomic Analysis 0:46 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 0:122 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 37107373 3 52 theme potential 318:326 arg1 mechanism 328:336 the potential mechanism 314:336 the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) 314:471 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 5 53 theme serum 697:701 arg1 levels 709:714 The obesity and serum lipid levels 681:714 levels 709:714 The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. 37107373 9 54 theme gut 1377:1379 arg1 microbiota 1381:1390 gut microbiota 1377:1390 gut microbiota 1377:1390 The function of gut microbiota mainly regulated lipid metabolism and amino acid metabolism. 37107373 11 55 theme acid 1581:1584 arg1 metabolism 1586:1595 linoleic acid metabolism 1572:1595 linoleic acid metabolism 1572:1595 Furthermore, linoleic acid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and the phenylalanine metabolism pathway played a role in improving obesity in those treated with SRP. 37107373 1 56 theme Gut 124:126 arg1 microbiota 128:137 Gut microbiota 124:137 Gut microbiota 124:137 Gut microbiota plays an important role in the pathophysiology of obesity. 37107373 10 57 theme anti-obesity 1531:1542 arg1 effect 1544:1549 the anti-obesity effect 1527:1549 the anti-obesity effect of SRP 1527:1556 The untargeted metabolomics indicated that 36 metabolites were related to the anti-obesity effect of SRP. 37107373 4 58 theme weeks 529:533 arg1 intervention 572:583 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention 527:583 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention 527:583 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 11 59 theme metabolism 1674:1683 arg1 pathway 1685:1691 the phenylalanine metabolism pathway 1656:1691 the phenylalanine metabolism pathway 1656:1691 Furthermore, linoleic acid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and the phenylalanine metabolism pathway played a role in improving obesity in those treated with SRP. 37107373 8 60 theme reuteri 1315:1321 arg1 abundance 1288:1296 the abundance 1284:1296 the abundance of Lactobacillus reuteri and Staphylococcus xylosus 1284:1348 At the species level, the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus increased, while the abundance of Lactobacillus reuteri and Staphylococcus xylosus decreased. 37107373 2 61 theme further 275:281 arg1 study 283:287 further study 275:287 further study 275:287 Fungal polysaccharide can improve obesity, but the potential mechanism needs further study. 37107373 6 62 theme Firmicutes 1004:1013 arg1 ratio 995:999 the ratio 991:999 the ratio of Firmicutes to Bacteroides 991:1028 SRP improved the composition and function of gut microbiota in rats fed with a high-fat diet, and decreased the ratio of Firmicutes to Bacteroides at the phylum level. 37107373 6 63 theme microbiota 932:941 arg1 composition 900:910 composition 900:910 composition 900:910 SRP improved the composition and function of gut microbiota in rats fed with a high-fat diet, and decreased the ratio of Firmicutes to Bacteroides at the phylum level. 37107373 6 63 theme microbiota 932:941 arg1 function 916:923 function 916:923 function 916:923 SRP improved the composition and function of gut microbiota in rats fed with a high-fat diet, and decreased the ratio of Firmicutes to Bacteroides at the phylum level. 37107373 11 64 theme tryptophan 1627:1636 arg1 biosynthesis 1638:1649 phenylalanine, tyrosine, and tryptophan biosynthesis 1598:1649 phenylalanine, tyrosine, and tryptophan biosynthesis 1598:1649 Furthermore, linoleic acid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and the phenylalanine metabolism pathway played a role in improving obesity in those treated with SRP. 37107373 4 65 theme metabolomics 659:670 arg1 index 610:614 the related index 598:614 the related index of obesity, gut microbiota, and untargeted metabolomics of rats 598:678 After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. 37107373 6 66 theme gut 928:930 arg1 microbiota 932:941 gut microbiota 928:941 gut microbiota 928:941 SRP improved the composition and function of gut microbiota in rats fed with a high-fat diet, and decreased the ratio of Firmicutes to Bacteroides at the phylum level. 37107373 0 67 theme Sporisorium 65:75 arg1 Polysaccharide 87:100 Sporisorium reilianum Polysaccharide 65:100 Sporisorium reilianum Polysaccharide 65:100 Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. 37107373 2 68 theme Fungal 198:203 arg1 polysaccharide 205:218 Fungal polysaccharide 198:218 Fungal polysaccharide 198:218 Fungal polysaccharide can improve obesity, but the potential mechanism needs further study. 37107373 3 69 theme untargeted 496:505 arg1 metabolomics 507:518 untargeted metabolomics 496:518 untargeted metabolomics 496:518 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 3 70 theme male 412:415 arg1 rats 437:440 male Sprague Dawley (SD) rats 412:440 male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) 412:471 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 2 71 theme potential 249:257 arg1 mechanism 259:267 the potential mechanism 245:267 the potential mechanism 245:267 Fungal polysaccharide can improve obesity, but the potential mechanism needs further study. 37107373 9 72 theme amino 1430:1434 arg1 metabolism 1441:1450 amino acid metabolism 1430:1450 amino acid metabolism 1430:1450 The function of gut microbiota mainly regulated lipid metabolism and amino acid metabolism. 37107373 11 73 theme tyrosine 1613:1620 arg1 biosynthesis 1638:1649 phenylalanine, tyrosine, and tryptophan biosynthesis 1598:1649 phenylalanine, tyrosine, and tryptophan biosynthesis 1598:1649 Furthermore, linoleic acid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and the phenylalanine metabolism pathway played a role in improving obesity in those treated with SRP. 37107373 3 74 from mechanism 328:336 arg1 SRP 385:387 SRP 385:387 SRP 385:387 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 37107373 3 74 from mechanism 328:336 arg1 reilianum 374:382 Sporisorium reilianum 362:382 Sporisorium reilianum (SRP) 362:388 This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. 36160989 12 0 from that 1991:1994 arg1 efficiency 1914:1923 the saccharification efficiency 1893:1923 the saccharification efficiency of greenhouse- and field-grown WT diploids 1893:1966 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 12 0 from that 1991:1994 arg1 different 1976:1984 different 1976:1984 different 1976:1984 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 7 1 theme field-grown 1201:1211 arg1 trees 1213:1217 both greenhouse- and field-grown trees 1180:1217 both greenhouse- and field-grown trees 1180:1217 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 36160989 7 2 theme whole 1099:1103 arg1 duplication 1112:1122 a whole genome duplication 1097:1122 a whole genome duplication of poplar 1097:1132 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 36160989 5 3 from tetraploids 953:963 arg1 research 933:940 tree biotechnology research 914:940 tree biotechnology research 914:940 INRA 717-1B4, a commonly used model clone in tree biotechnology research, and hpCAD tetraploids were generated and grown in the greenhouse. 36160989 13 4 theme alkaline 2119:2126 arg1 pretreatment 2128:2139 alkaline pretreatment 2119:2139 alkaline pretreatment 2119:2139 Upon alkaline pretreatment, the saccharification yield of diploids was similar to that of tetraploids for all genotypes and growth conditions tested. 36160989 12 5 theme diploids 1959:1966 arg1 efficiency 1914:1923 the saccharification efficiency 1893:1923 the saccharification efficiency of greenhouse- and field-grown WT diploids 1893:1966 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 12 5 theme diploids 1959:1966 arg1 different 1976:1984 different 1976:1984 different 1976:1984 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 10 6 theme poplars 1539:1545 arg1 content 1505:1511 the lignin content 1494:1511 the lignin content of field-grown tetraploid poplars 1494:1545 More specifically, the lignin content of field-grown tetraploid poplars was increased at the expense of matrix polysaccharides. 36160989 14 7 theme biomass 2421:2427 arg1 composition 2429:2439 improved biomass composition 2412:2439 improved biomass composition 2412:2439 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 4 8 theme P. 857:858 arg1 treatment 813:821 a colchicine treatment 800:821 a colchicine treatment 800:821 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 4 8 theme P. 857:858 arg1 cv 865:866 wild-type (WT) Populus tremula x P. alba cv 824:866 wild-type (WT) Populus tremula x P. alba cv 824:866 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 12 9 theme greenhouse-grown 2087:2102 arg1 diploids 2104:2111 greenhouse-grown diploids 2087:2111 greenhouse-grown diploids 2087:2111 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 10 10 theme field-grown 1516:1526 arg1 poplars 1539:1545 field-grown tetraploid poplars 1516:1545 field-grown tetraploid poplars 1516:1545 More specifically, the lignin content of field-grown tetraploid poplars was increased at the expense of matrix polysaccharides. 36160989 14 11 theme hpCAD 2331:2335 arg1 poplar 2337:2342 hpCAD poplar 2331:2342 hpCAD poplar 2331:2342 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 2 12 theme Arabidopsis 279:289 arg1 tetraploids 291:301 Arabidopsis tetraploids 279:301 Arabidopsis tetraploids 279:301 In Arabidopsis tetraploids, an increase in biomass yield was accompanied by a reduction in lignin content and, as a result, a higher saccharification efficiency was achieved compared with diploid controls. 36160989 9 13 theme biomass 1391:1397 arg1 composition 1399:1409 the biomass composition 1387:1409 the biomass composition of field-grown, but not of greenhouse-grown tetraploid poplars 1387:1472 In addition, the chromosome doubling altered the biomass composition of field-grown, but not of greenhouse-grown tetraploid poplars. 36160989 12 14 theme greenhouse- 1928:1938 arg1 diploids 1959:1966 greenhouse- and field-grown WT diploids 1928:1966 greenhouse- and field-grown WT diploids 1928:1966 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 2 15 from reduction 354:362 arg1 content 374:380 lignin content 367:380 lignin content 367:380 In Arabidopsis tetraploids, an increase in biomass yield was accompanied by a reduction in lignin content and, as a result, a higher saccharification efficiency was achieved compared with diploid controls. 36160989 3 16 theme genome 774:779 arg1 duplication 781:791 a whole genome duplication 766:791 a whole genome duplication 766:791 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 2 17 theme biomass 319:325 arg1 yield 327:331 biomass yield 319:331 biomass yield 319:331 In Arabidopsis tetraploids, an increase in biomass yield was accompanied by a reduction in lignin content and, as a result, a higher saccharification efficiency was achieved compared with diploid controls. 36160989 12 18 theme field-grown 1944:1954 arg1 diploids 1959:1966 greenhouse- and field-grown WT diploids 1928:1966 greenhouse- and field-grown WT diploids 1928:1966 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 8 19 theme field-grown 1232:1242 arg1 tetraploids 1247:1257 field-grown WT tetraploids 1232:1257 field-grown WT tetraploids developed a brittle apex phenotype, i.e., their tip 1232:1309 Strikingly, field-grown WT tetraploids developed a brittle apex phenotype, i.e., their tip broke off just below the apex. 36160989 4 20 dep Populus 839:845 arg1 tremula 847:853 tremula 847:853 tremula 847:853 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 11 21 from increase 1608:1615 arg1 deposition 1627:1636 lignin deposition 1620:1636 lignin deposition in biomass 1620:1647 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 10 22 theme polysaccharides 1586:1600 arg1 expense 1568:1574 the expense 1564:1574 the expense of matrix polysaccharides 1564:1600 More specifically, the lignin content of field-grown tetraploid poplars was increased at the expense of matrix polysaccharides. 36160989 0 23 theme apex 145:148 arg1 phenotype 150:158 a brittle apex phenotype 135:158 a brittle apex phenotype in field-grown wild types 135:184 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 3 24 theme enhanced 593:600 arg1 yield 619:623 the enhanced saccharification yield 589:623 the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 589:733 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 12 25 theme greenhouse-grown 2028:2043 arg1 tetraploids 2051:2061 greenhouse-grown hpCAD tetraploids 2028:2061 greenhouse-grown hpCAD tetraploids 2028:2061 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 9 26 theme greenhouse-grown 1438:1453 arg1 poplars 1466:1472 greenhouse-grown tetraploid poplars 1438:1472 greenhouse-grown tetraploid poplars 1438:1472 In addition, the chromosome doubling altered the biomass composition of field-grown, but not of greenhouse-grown tetraploid poplars. 36160989 8 27 theme apex 1279:1282 arg1 phenotype 1284:1292 a brittle apex phenotype 1269:1292 a brittle apex phenotype 1269:1292 Strikingly, field-grown WT tetraploids developed a brittle apex phenotype, i.e., their tip broke off just below the apex. 36160989 0 28 theme wild 175:178 arg1 types 180:184 field-grown wild types 163:184 field-grown wild types 163:184 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 3 29 theme alkaline 630:637 arg1 pretreatment 639:650 alkaline pretreatment 630:650 alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 630:733 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 5 30 from 717-1B4 874:880 arg1 research 933:940 tree biotechnology research 914:940 tree biotechnology research 914:940 INRA 717-1B4, a commonly used model clone in tree biotechnology research, and hpCAD tetraploids were generated and grown in the greenhouse. 36160989 9 31 theme poplars 1466:1472 arg1 composition 1399:1409 the biomass composition 1387:1409 the biomass composition of field-grown, but not of greenhouse-grown tetraploid poplars 1387:1472 In addition, the chromosome doubling altered the biomass composition of field-grown, but not of greenhouse-grown tetraploid poplars. 36160989 5 32 theme tree 914:917 arg1 research 933:940 tree biotechnology research 914:940 tree biotechnology research 914:940 INRA 717-1B4, a commonly used model clone in tree biotechnology research, and hpCAD tetraploids were generated and grown in the greenhouse. 36160989 14 33 theme whole 2289:2293 arg1 duplication 2302:2312 a whole genome duplication 2287:2312 a whole genome duplication in hybrid WT and hpCAD poplar 2287:2342 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 11 34 theme phenotype 1698:1706 arg1 cause 1663:1667 the cause 1659:1667 the cause of the observed brittle apex phenotype 1659:1706 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 11 34 theme phenotype 1698:1706 arg1 increase 1608:1615 This increase 1603:1615 This increase in lignin deposition in biomass 1603:1647 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 0 35 theme DEHYDROGENASE1-downregulated 59:86 arg1 poplar 95:100 wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 28:100 wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 28:100 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 0 36 theme poplar 95:100 arg1 duplication 13:23 Whole genome duplication 0:23 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 0:100 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 5 37 theme model 899:903 arg1 clone 905:909 a commonly used model clone 883:909 a commonly used model clone in tree biotechnology research 883:940 INRA 717-1B4, a commonly used model clone in tree biotechnology research, and hpCAD tetraploids were generated and grown in the greenhouse. 36160989 12 38 theme hpCAD 2045:2049 arg1 tetraploids 2051:2061 greenhouse-grown hpCAD tetraploids 2028:2061 greenhouse-grown hpCAD tetraploids 2028:2061 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 11 39 theme major 1719:1723 arg1 differences 1725:1735 no major differences 1716:1735 no major differences in stem anatomy or in mechanical properties 1716:1779 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 0 40 theme biomass 110:116 arg1 yield 118:122 biomass yield 110:122 biomass yield 110:122 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 12 41 theme biomass 1871:1877 arg1 pretreatment 1879:1890 biomass pretreatment 1871:1890 biomass pretreatment 1871:1890 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 5 42 theme biotechnology 919:931 arg1 research 933:940 tree biotechnology research 914:940 tree biotechnology research 914:940 INRA 717-1B4, a commonly used model clone in tree biotechnology research, and hpCAD tetraploids were generated and grown in the greenhouse. 36160989 4 43 theme colchicine 802:811 arg1 treatment 813:821 a colchicine treatment 800:821 a colchicine treatment 800:821 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 4 43 theme colchicine 802:811 arg1 cv 865:866 wild-type (WT) Populus tremula x P. alba cv 824:866 wild-type (WT) Populus tremula x P. alba cv 824:866 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 11 44 from deposition 1627:1636 arg1 biomass 1641:1647 biomass 1641:1647 biomass 1641:1647 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 0 45 theme hybrid 88:93 arg1 poplar 95:100 wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 28:100 wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 28:100 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 0 46 theme Whole 0:4 arg1 duplication 13:23 Whole genome duplication 0:23 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 0:100 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 5 47 from clone 905:909 arg1 research 933:940 tree biotechnology research 914:940 tree biotechnology research 914:940 INRA 717-1B4, a commonly used model clone in tree biotechnology research, and hpCAD tetraploids were generated and grown in the greenhouse. 36160989 2 48 theme higher 402:407 arg1 efficiency 426:435 a higher saccharification efficiency 400:435 a higher saccharification efficiency 400:435 In Arabidopsis tetraploids, an increase in biomass yield was accompanied by a reduction in lignin content and, as a result, a higher saccharification efficiency was achieved compared with diploid controls. 36160989 2 48 theme higher 402:407 arg1 result 392:397 a result 390:397 a result 390:397 In Arabidopsis tetraploids, an increase in biomass yield was accompanied by a reduction in lignin content and, as a result, a higher saccharification efficiency was achieved compared with diploid controls. 36160989 5 49 theme hpCAD 947:951 arg1 tetraploids 953:963 hpCAD tetraploids 947:963 hpCAD tetraploids 947:963 INRA 717-1B4, a commonly used model clone in tree biotechnology research, and hpCAD tetraploids were generated and grown in the greenhouse. 36160989 3 50 theme CINNAMYL 677:684 arg1 poplar 728:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 1 51 dep potential 191:199 arg1 increase 232:239 increase 232:239 to increase plant biomass yield 229:259 The potential of whole genome duplication to increase plant biomass yield is well-known. 36160989 7 52 theme poplar 1127:1132 arg1 duplication 1112:1122 a whole genome duplication 1097:1122 a whole genome duplication of poplar 1097:1132 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 36160989 13 53 theme diploids 2172:2179 arg1 similar 2185:2191 similar 2185:2191 similar 2185:2191 Upon alkaline pretreatment, the saccharification yield of diploids was similar to that of tetraploids for all genotypes and growth conditions tested. 36160989 13 53 theme diploids 2172:2179 arg1 yield 2163:2167 the saccharification yield 2142:2167 the saccharification yield of diploids 2142:2179 Upon alkaline pretreatment, the saccharification yield of diploids was similar to that of tetraploids for all genotypes and growth conditions tested. 36160989 0 54 theme wild-type 28:36 arg1 poplar 95:100 wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 28:100 wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 28:100 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 6 55 theme WT 1022:1023 arg1 poplars 1036:1042 WT tetraploid poplars 1022:1042 WT tetraploid poplars 1022:1042 In parallel, WT tetraploid poplars were grown in the field. 36160989 0 56 theme CINNAMYL 42:49 arg1 poplar 95:100 wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 28:100 wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 28:100 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 11 57 theme apex 1693:1696 arg1 phenotype 1698:1706 the observed brittle apex phenotype 1672:1706 the observed brittle apex phenotype 1672:1706 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 14 58 theme biomass 2390:2396 arg1 yield 2398:2402 biomass yield 2390:2402 biomass yield 2390:2402 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 14 59 from duplication 2302:2312 arg1 WT 2324:2325 hybrid WT 2317:2325 hybrid WT 2317:2325 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 14 59 from duplication 2302:2312 arg1 poplar 2337:2342 hpCAD poplar 2331:2342 hpCAD poplar 2331:2342 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 3 60 theme DEHYDROGENASE1 694:707 arg1 poplar 728:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 4 61 dep wild-type 824:832 arg1 WT 835:836 WT 835:836 WT 835:836 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 1 62 theme biomass 247:253 arg1 yield 255:259 plant biomass yield 241:259 plant biomass yield 241:259 The potential of whole genome duplication to increase plant biomass yield is well-known. 36160989 0 63 theme ALCOHOL 51:57 arg1 poplar 95:100 wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 28:100 wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 28:100 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 10 64 theme lignin 1498:1503 arg1 content 1505:1511 the lignin content 1494:1511 the lignin content of field-grown tetraploid poplars 1494:1545 More specifically, the lignin content of field-grown tetraploid poplars was increased at the expense of matrix polysaccharides. 36160989 11 65 theme lignin 1620:1625 arg1 deposition 1627:1636 lignin deposition 1620:1636 lignin deposition in biomass 1620:1647 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 11 66 theme WT 1823:1824 arg1 poplars 1826:1832 di- and tetraploid WT poplars 1804:1832 di- and tetraploid WT poplars grown in the field 1804:1851 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 7 67 theme trees 1213:1217 arg1 yield 1171:1175 the biomass yield 1159:1175 the biomass yield of both greenhouse- and field-grown trees 1159:1217 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 36160989 3 68 theme transgenic 717:726 arg1 poplar 728:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 9 69 theme doubling 1370:1377 arg1 chromosome 1359:1368 the chromosome doubling 1355:1377 the chromosome doubling 1355:1377 In addition, the chromosome doubling altered the biomass composition of field-grown, but not of greenhouse-grown tetraploid poplars. 36160989 12 70 theme WT 1956:1957 arg1 diploids 1959:1966 greenhouse- and field-grown WT diploids 1928:1966 greenhouse- and field-grown WT diploids 1928:1966 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 10 71 theme tetraploid 1528:1537 arg1 poplars 1539:1545 field-grown tetraploid poplars 1516:1545 field-grown tetraploid poplars 1516:1545 More specifically, the lignin content of field-grown tetraploid poplars was increased at the expense of matrix polysaccharides. 36160989 14 72 theme improved 2412:2419 arg1 composition 2429:2439 improved biomass composition 2412:2439 improved biomass composition 2412:2439 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 7 73 dep Arabidopsis 1084:1094 arg1 contrast 1072:1079 contrast 1072:1079 contrast 1072:1079 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 36160989 7 74 contain had 1134:1136 arg2 impact 1149:1154 a negative impact 1138:1154 a negative impact 1138:1154 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 36160989 7 74 contain had 1134:1136 arg1 duplication 1112:1122 a whole genome duplication 1097:1122 a whole genome duplication of poplar 1097:1132 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 36160989 11 75 theme mechanical 1759:1768 arg1 properties 1770:1779 mechanical properties 1759:1779 mechanical properties 1759:1779 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 0 76 theme brittle 137:143 arg1 phenotype 150:158 a brittle apex phenotype 135:158 a brittle apex phenotype in field-grown wild types 135:184 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 14 77 theme hybrid 2317:2322 arg1 WT 2324:2325 hybrid WT 2317:2325 hybrid WT 2317:2325 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 9 78 theme field-grown 1414:1424 arg1 composition 1399:1409 the biomass composition 1387:1409 the biomass composition of field-grown, but not of greenhouse-grown tetraploid poplars 1387:1472 In addition, the chromosome doubling altered the biomass composition of field-grown, but not of greenhouse-grown tetraploid poplars. 36160989 11 79 from differences 1725:1735 arg1 anatomy 1745:1751 stem anatomy 1740:1751 stem anatomy 1740:1751 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 11 79 from differences 1725:1735 arg1 properties 1770:1779 mechanical properties 1759:1779 mechanical properties 1759:1779 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 13 80 theme growth 2238:2243 arg1 conditions 2245:2254 growth conditions 2238:2254 growth conditions 2238:2254 Upon alkaline pretreatment, the saccharification yield of diploids was similar to that of tetraploids for all genotypes and growth conditions tested. 36160989 3 81 theme whole 768:772 arg1 duplication 781:791 a whole genome duplication 766:791 a whole genome duplication 766:791 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 1 82 theme duplication 217:227 arg1 potential 191:199 The potential 187:199 The potential of whole genome duplication to increase plant biomass yield 187:259 The potential of whole genome duplication to increase plant biomass yield is well-known. 36160989 1 82 theme duplication 217:227 arg1 well-known 264:273 well-known 264:273 well-known 264:273 The potential of whole genome duplication to increase plant biomass yield is well-known. 36160989 8 83 theme WT 1244:1245 arg1 tetraploids 1247:1257 field-grown WT tetraploids 1232:1257 field-grown WT tetraploids developed a brittle apex phenotype, i.e., their tip 1232:1309 Strikingly, field-grown WT tetraploids developed a brittle apex phenotype, i.e., their tip broke off just below the apex. 36160989 10 84 theme matrix 1579:1584 arg1 polysaccharides 1586:1600 matrix polysaccharides 1579:1600 matrix polysaccharides 1579:1600 More specifically, the lignin content of field-grown tetraploid poplars was increased at the expense of matrix polysaccharides. 36160989 0 85 theme field-grown 163:173 arg1 types 180:184 field-grown wild types 163:184 field-grown wild types 163:184 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 12 86 theme saccharification 1897:1912 arg1 efficiency 1914:1923 the saccharification efficiency 1893:1923 the saccharification efficiency of greenhouse- and field-grown WT diploids 1893:1966 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 12 86 theme saccharification 1897:1912 arg1 different 1976:1984 different 1976:1984 different 1976:1984 Finally, without biomass pretreatment, the saccharification efficiency of greenhouse- and field-grown WT diploids was not different from that of tetraploids, whereas that of greenhouse-grown hpCAD tetraploids was higher than that of greenhouse-grown diploids. 36160989 3 87 theme hpCAD 710:714 arg1 poplar 728:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 9 88 theme tetraploid 1455:1464 arg1 poplars 1466:1472 greenhouse-grown tetraploid poplars 1438:1472 greenhouse-grown tetraploid poplars 1438:1472 In addition, the chromosome doubling altered the biomass composition of field-grown, but not of greenhouse-grown tetraploid poplars. 36160989 8 89 theme brittle 1271:1277 arg1 phenotype 1284:1292 a brittle apex phenotype 1269:1292 a brittle apex phenotype 1269:1292 Strikingly, field-grown WT tetraploids developed a brittle apex phenotype, i.e., their tip broke off just below the apex. 36160989 14 90 theme genome 2295:2300 arg1 duplication 2302:2312 a whole genome duplication 2287:2312 a whole genome duplication in hybrid WT and hpCAD poplar 2287:2342 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 7 91 theme greenhouse- 1185:1195 arg1 trees 1213:1217 both greenhouse- and field-grown trees 1180:1217 both greenhouse- and field-grown trees 1180:1217 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 36160989 3 92 theme saccharification 602:617 arg1 yield 619:623 the enhanced saccharification yield 589:623 the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 589:733 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 1 93 theme whole 204:208 arg1 duplication 217:227 whole genome duplication 204:227 whole genome duplication 204:227 The potential of whole genome duplication to increase plant biomass yield is well-known. 36160989 14 94 from improvements 2374:2385 arg1 yield 2398:2402 biomass yield 2390:2402 biomass yield 2390:2402 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 5 95 theme used 894:897 arg1 clone 905:909 a commonly used model clone 883:909 a commonly used model clone in tree biotechnology research 883:940 INRA 717-1B4, a commonly used model clone in tree biotechnology research, and hpCAD tetraploids were generated and grown in the greenhouse. 36160989 2 96 from increase 307:314 arg1 yield 327:331 biomass yield 319:331 biomass yield 319:331 In Arabidopsis tetraploids, an increase in biomass yield was accompanied by a reduction in lignin content and, as a result, a higher saccharification efficiency was achieved compared with diploid controls. 36160989 11 97 theme stem 1740:1743 arg1 anatomy 1745:1751 stem anatomy 1740:1751 stem anatomy 1740:1751 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 7 98 theme biomass 1163:1169 arg1 yield 1171:1175 the biomass yield 1159:1175 the biomass yield of both greenhouse- and field-grown trees 1159:1217 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 36160989 11 99 theme di- 1804:1806 arg1 poplars 1826:1832 di- and tetraploid WT poplars 1804:1832 di- and tetraploid WT poplars grown in the field 1804:1851 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 1 100 theme genome 210:215 arg1 duplication 217:227 whole genome duplication 204:227 whole genome duplication 204:227 The potential of whole genome duplication to increase plant biomass yield is well-known. 36160989 13 101 theme saccharification 2146:2161 arg1 similar 2185:2191 similar 2185:2191 similar 2185:2191 Upon alkaline pretreatment, the saccharification yield of diploids was similar to that of tetraploids for all genotypes and growth conditions tested. 36160989 13 101 theme saccharification 2146:2161 arg1 yield 2163:2167 the saccharification yield 2142:2167 the saccharification yield of diploids 2142:2179 Upon alkaline pretreatment, the saccharification yield of diploids was similar to that of tetraploids for all genotypes and growth conditions tested. 36160989 0 102 theme genome 6:11 arg1 duplication 13:23 Whole genome duplication 0:23 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar 0:100 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 11 103 theme observed 1676:1683 arg1 phenotype 1698:1706 the observed brittle apex phenotype 1672:1706 the observed brittle apex phenotype 1672:1706 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 4 104 dep P. 857:858 arg1 alba 860:863 alba 860:863 alba 860:863 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 2 105 theme saccharification 409:424 arg1 efficiency 426:435 a higher saccharification efficiency 400:435 a higher saccharification efficiency 400:435 In Arabidopsis tetraploids, an increase in biomass yield was accompanied by a reduction in lignin content and, as a result, a higher saccharification efficiency was achieved compared with diploid controls. 36160989 2 105 theme saccharification 409:424 arg1 result 392:397 a result 390:397 a result 390:397 In Arabidopsis tetraploids, an increase in biomass yield was accompanied by a reduction in lignin content and, as a result, a higher saccharification efficiency was achieved compared with diploid controls. 36160989 3 106 theme hairpin-downregulated 655:675 arg1 poplar 728:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 13 107 dep genotypes 2224:2232 arg1 all 2220:2222 all 2220:2222 all 2220:2222 Upon alkaline pretreatment, the saccharification yield of diploids was similar to that of tetraploids for all genotypes and growth conditions tested. 36160989 5 108 theme INRA 869:872 arg1 717-1B4 874:880 INRA 717-1B4 869:880 INRA 717-1B4 869:880 INRA 717-1B4, a commonly used model clone in tree biotechnology research, and hpCAD tetraploids were generated and grown in the greenhouse. 36160989 8 109 dep tip 1307:1309 arg1 i.e. 1295:1298 i.e. 1295:1298 i.e. 1295:1298 Strikingly, field-grown WT tetraploids developed a brittle apex phenotype, i.e., their tip broke off just below the apex. 36160989 6 110 theme tetraploid 1025:1034 arg1 poplars 1036:1042 WT tetraploid poplars 1022:1042 WT tetraploid poplars 1022:1042 In parallel, WT tetraploid poplars were grown in the field. 36160989 2 111 theme diploid 464:470 arg1 controls 472:479 diploid controls 464:479 diploid controls 464:479 In Arabidopsis tetraploids, an increase in biomass yield was accompanied by a reduction in lignin content and, as a result, a higher saccharification efficiency was achieved compared with diploid controls. 36160989 7 112 theme genome 1105:1110 arg1 duplication 1112:1122 a whole genome duplication 1097:1122 a whole genome duplication of poplar 1097:1132 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 36160989 11 113 theme brittle 1685:1691 arg1 phenotype 1698:1706 the observed brittle apex phenotype 1672:1706 the observed brittle apex phenotype 1672:1706 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 4 114 theme Populus 839:845 arg1 treatment 813:821 a colchicine treatment 800:821 a colchicine treatment 800:821 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 4 114 theme Populus 839:845 arg1 cv 865:866 wild-type (WT) Populus tremula x P. alba cv 824:866 wild-type (WT) Populus tremula x P. alba cv 824:866 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 11 115 theme tetraploid 1812:1821 arg1 poplars 1826:1832 di- and tetraploid WT poplars 1804:1832 di- and tetraploid WT poplars grown in the field 1804:1851 This increase in lignin deposition in biomass is likely the cause of the observed brittle apex phenotype, though no major differences in stem anatomy or in mechanical properties could be found between di- and tetraploid WT poplars grown in the field. 36160989 0 116 from phenotype 150:158 arg1 types 180:184 field-grown wild types 163:184 field-grown wild types 163:184 Whole genome duplication of wild-type and CINNAMYL ALCOHOL DEHYDROGENASE1-downregulated hybrid poplar reduces biomass yield and causes a brittle apex phenotype in field-grown wild types. 36160989 3 117 theme ALCOHOL 686:692 arg1 poplar 728:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 655:733 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 2 118 theme lignin 367:372 arg1 content 374:380 lignin content 367:380 lignin content 367:380 In Arabidopsis tetraploids, an increase in biomass yield was accompanied by a reduction in lignin content and, as a result, a higher saccharification efficiency was achieved compared with diploid controls. 36160989 1 119 theme plant 241:245 arg1 yield 255:259 plant biomass yield 241:259 plant biomass yield 241:259 The potential of whole genome duplication to increase plant biomass yield is well-known. 36160989 14 120 theme saccharification 2453:2468 arg1 performance 2470:2480 saccharification performance 2453:2480 saccharification performance 2453:2480 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 3 121 theme poplar 728:733 arg1 pretreatment 639:650 alkaline pretreatment 630:650 alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar 630:733 Here, we evaluated whether the results obtained in Arabidopsis could be translated into poplar and whether the enhanced saccharification yield upon alkaline pretreatment of hairpin-downregulated CINNAMYL ALCOHOL DEHYDROGENASE1 (hpCAD) transgenic poplar could be further improved upon a whole genome duplication. 36160989 4 122 theme wild-type 824:832 arg1 treatment 813:821 a colchicine treatment 800:821 a colchicine treatment 800:821 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 4 122 theme wild-type 824:832 arg1 cv 865:866 wild-type (WT) Populus tremula x P. alba cv 824:866 wild-type (WT) Populus tremula x P. alba cv 824:866 Using a colchicine treatment, wild-type (WT) Populus tremula x P. alba cv. 36160989 14 123 theme further 2366:2372 arg1 improvements 2374:2385 further improvements 2366:2385 further improvements in biomass yield 2366:2402 This study showed that a whole genome duplication in hybrid WT and hpCAD poplar did neither result in further improvements in biomass yield, nor in improved biomass composition and, hence, saccharification performance. 36160989 7 124 theme negative 1140:1147 arg1 impact 1149:1154 a negative impact 1138:1154 a negative impact 1138:1154 In contrast to Arabidopsis, a whole genome duplication of poplar had a negative impact on the biomass yield of both greenhouse- and field-grown trees. 35426561 3 0 theme manufacturing 560:572 arg1 factories 574:582 tea manufacturing factories 556:582 tea manufacturing factories enriched in lignocellulose 556:609 Tea waste is a by-product from tea manufacturing factories enriched in lignocellulose is used to extract two types of humic fractions. 35426561 1 1 theme humic 277:281 arg1 substances 283:292 humic substances 277:292 humic substances 277:292 Emerging demand for humic substances escalated the short supply of coal-related resources from which humic substances are extracted in large quantities for various applications. 35426561 11 2 used used 1814:1817 arg2 biostimulant 1849:1860 a potential plant biostimulant 1831:1860 a potential plant biostimulant 1831:1860 Our findings revealed that TWDHLS could be used not only as a potential plant biostimulant but also as a better substitute for humic substances. 35426561 11 2 used used 1814:1817 arg2 TWDHLS 1798:1803 TWDHLS 1798:1803 TWDHLS 1798:1803 Our findings revealed that TWDHLS could be used not only as a potential plant biostimulant but also as a better substitute for humic substances. 35426561 11 2 used used 1814:1817 arg2 better 1876:1881 better 1876:1881 better 1876:1881 Our findings revealed that TWDHLS could be used not only as a potential plant biostimulant but also as a better substitute for humic substances. 35426561 3 3 from factories 574:582 arg1 by-product 540:549 a by-product 538:549 a by-product from tea manufacturing factories enriched in lignocellulose 538:609 Tea waste is a by-product from tea manufacturing factories enriched in lignocellulose is used to extract two types of humic fractions. 35426561 3 3 from factories 574:582 arg1 waste 529:533 Tea waste 525:533 Tea waste 525:533 Tea waste is a by-product from tea manufacturing factories enriched in lignocellulose is used to extract two types of humic fractions. 35426561 3 4 theme tea 556:558 arg1 factories 574:582 tea manufacturing factories 556:582 tea manufacturing factories enriched in lignocellulose 556:609 Tea waste is a by-product from tea manufacturing factories enriched in lignocellulose is used to extract two types of humic fractions. 35426561 10 5 theme application 1590:1600 arg1 TWDHLS 1602:1607 soil application TWDHLS 1585:1607 soil application TWDHLS at 80 mg L-1 concentration 1585:1634 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 5 6 theme biological 878:887 arg1 activity 889:896 biological activity 878:896 biological activity 878:896 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 6 7 theme carbon 1175:1180 arg1 distribution 1182:1193 similar carbon distribution 1167:1193 similar carbon distribution 1167:1193 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 10 8 theme structural 1748:1757 arg1 properties 1759:1768 their structural properties 1742:1768 their structural properties 1742:1768 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 10 9 theme similar 1694:1700 arg1 results 1650:1656 better results 1643:1656 better results on the growth of tea nursery plants similar to CHA 1643:1707 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 10 10 theme L-1 1618:1620 arg1 concentration 1622:1634 80 mg L-1 concentration 1612:1634 80 mg L-1 concentration 1612:1634 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 9 11 theme biological 1447:1456 arg1 activity 1458:1465 The biological activity 1443:1465 The biological activity of TWDHLS and CHA 1443:1483 The biological activity of TWDHLS and CHA was studied at five different concentrations (0, 20, 40, 80, and 160 mg L-1). 35426561 9 12 theme different 1505:1513 arg1 concentrations 1515:1528 five different concentrations 1500:1528 five different concentrations (0, 20, 40, 80, and 160 mg L-1) 1500:1560 The biological activity of TWDHLS and CHA was studied at five different concentrations (0, 20, 40, 80, and 160 mg L-1). 35426561 9 12 theme different 1505:1513 arg1 L-1 1557:1559 0, 20, 40, 80, and 160 mg L-1 1531:1559 0, 20, 40, 80, and 160 mg L-1 1531:1559 The biological activity of TWDHLS and CHA was studied at five different concentrations (0, 20, 40, 80, and 160 mg L-1). 35426561 4 13 theme fulvic 748:753 arg1 acids 755:759 unpurified humic and fulvic acids 727:759 unpurified humic and fulvic acids called as humic-like substances (HLS) 727:797 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 7 14 attach presence 1270:1277 arg1 TWDHLS 1307:1312 TWDHLS 1307:1312 TWDHLS 1307:1312 The presence of more stable compounds in TWDHLS contribute to its recalcitrant nature. 35426561 7 14 attach presence 1270:1277 arg2 compounds 1294:1302 more stable compounds 1282:1302 more stable compounds 1282:1302 The presence of more stable compounds in TWDHLS contribute to its recalcitrant nature. 35426561 0 15 theme biological 155:164 arg1 activity 166:173 biological activity 155:173 biological activity 155:173 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 3 16 theme humic 643:647 arg1 fractions 649:657 humic fractions 643:657 humic fractions 643:657 Tea waste is a by-product from tea manufacturing factories enriched in lignocellulose is used to extract two types of humic fractions. 35426561 10 17 from variation 1729:1737 arg1 properties 1759:1768 their structural properties 1742:1768 their structural properties 1742:1768 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 6 18 theme Elemental 1033:1041 arg1 analysis 1043:1050 Elemental analysis 1033:1050 Elemental analysis 1033:1050 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 0 19 from substances 90:99 arg1 properties 140:149 spectroscopic properties 126:149 spectroscopic properties 126:149 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 0 19 from substances 90:99 arg1 activity 166:173 biological activity 155:173 biological activity 155:173 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 0 19 from substances 90:99 arg1 composition 113:123 chemical composition 104:123 chemical composition 104:123 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 6 20 theme cellulosic 1215:1224 arg1 polysaccharides 1226:1240 cellulosic polysaccharides 1215:1240 cellulosic polysaccharides 1215:1240 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 3 21 theme Tea 525:527 arg1 by-product 540:549 a by-product 538:549 a by-product from tea manufacturing factories enriched in lignocellulose 538:609 Tea waste is a by-product from tea manufacturing factories enriched in lignocellulose is used to extract two types of humic fractions. 35426561 3 21 theme Tea 525:527 arg1 waste 529:533 Tea waste 525:533 Tea waste 525:533 Tea waste is a by-product from tea manufacturing factories enriched in lignocellulose is used to extract two types of humic fractions. 35426561 8 22 theme NMR 1353:1355 arg1 spectra 1357:1363 NMR spectra 1353:1363 NMR spectra of CHA 1353:1370 NMR spectra of CHA significantly varied with TWDHLS and were rich in aliphatic compounds. 35426561 5 23 theme waste 905:909 arg1 TWDHLS 942:947 TWDHLS 942:947 TWDHLS 942:947 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 23 theme waste 905:909 arg1 substances 930:939 tea waste derived humic-like substances 901:939 tea waste derived humic-like substances (TWDHLS) 901:948 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 4 24 theme humic 738:742 arg1 acids 755:759 unpurified humic and fulvic acids 727:759 unpurified humic and fulvic acids called as humic-like substances (HLS) 727:797 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 0 25 theme lignite-derived 68:82 arg1 substances 90:99 lignite-derived humic substances 68:99 lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity 68:173 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 1 26 theme Emerging 176:183 arg1 demand 185:190 Emerging demand 176:190 Emerging demand for humic substances 176:211 Emerging demand for humic substances escalated the short supply of coal-related resources from which humic substances are extracted in large quantities for various applications. 35426561 6 27 from polysaccharides 1226:1240 arg1 abundant 1203:1210 abundant 1203:1210 abundant 1203:1210 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 5 28 theme humic 992:996 arg1 CHA 1004:1006 CHA 1004:1006 CHA 1004:1006 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 28 theme humic 992:996 arg1 acid 998:1001 commercially available humic acid 969:1001 commercially available humic acid (CHA) extracted from lignite 969:1030 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 10 29 theme better 1643:1648 arg1 results 1650:1656 better results 1643:1656 better results on the growth of tea nursery plants similar to CHA 1643:1707 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 0 30 theme chemical 104:111 arg1 composition 113:123 chemical composition 104:123 chemical composition 104:123 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 4 31 theme humic-like 771:780 arg1 substances 782:791 humic-like substances 771:791 humic-like substances (HLS) 771:797 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 4 31 theme humic-like 771:780 arg1 HLS 794:796 HLS 794:796 HLS 794:796 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 5 32 theme CPMAS 842:846 arg1 properties 862:871 spectroscopic (13C CPMAS NMR and FTIR) properties 823:871 spectroscopic (13C CPMAS NMR and FTIR) properties 823:871 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 32 theme CPMAS 842:846 arg1 NMR 848:850 13C CPMAS NMR 838:850 13C CPMAS NMR 838:850 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 6 33 theme slight 1085:1090 arg1 differences 1092:1102 slight differences 1085:1102 slight differences between HLA and HLS 1085:1122 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 2 34 theme humic 478:482 arg1 substances 484:493 humic substances 478:493 humic substances 478:493 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 1 35 theme large 311:315 arg1 quantities 317:326 large quantities 311:326 large quantities for various applications 311:351 Emerging demand for humic substances escalated the short supply of coal-related resources from which humic substances are extracted in large quantities for various applications. 35426561 8 36 theme aliphatic 1422:1430 arg1 compounds 1432:1440 aliphatic compounds 1422:1440 aliphatic compounds 1422:1440 NMR spectra of CHA significantly varied with TWDHLS and were rich in aliphatic compounds. 35426561 0 37 theme tea 23:25 arg1 waste 27:31 tea waste 23:31 tea waste 23:31 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 10 38 from concentration 1622:1634 arg1 TWDHLS 1602:1607 soil application TWDHLS 1585:1607 soil application TWDHLS at 80 mg L-1 concentration 1585:1634 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 2 39 theme substances 379:388 arg1 Production 354:363 Production 354:363 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances 354:493 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 5 40 dep properties 862:871 arg1 properties 862:871 spectroscopic (13C CPMAS NMR and FTIR) properties 823:871 spectroscopic (13C CPMAS NMR and FTIR) properties 823:871 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 40 dep properties 862:871 arg1 FTIR 856:859 FTIR 856:859 FTIR 856:859 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 40 dep properties 862:871 arg1 NMR 848:850 13C CPMAS NMR 838:850 13C CPMAS NMR 838:850 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 10 41 theme tea 1675:1677 arg1 plants 1687:1692 tea nursery plants 1675:1692 tea nursery plants 1675:1692 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 2 42 from properties 464:473 arg1 similar 427:433 similar 427:433 similar 427:433 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 6 43 theme NMR 1131:1133 arg1 results 1135:1141 NMR results 1131:1141 NMR results 1131:1141 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 11 44 theme plant 1843:1847 arg1 TWDHLS 1798:1803 TWDHLS 1798:1803 TWDHLS 1798:1803 Our findings revealed that TWDHLS could be used not only as a potential plant biostimulant but also as a better substitute for humic substances. 35426561 11 44 theme plant 1843:1847 arg1 biostimulant 1849:1860 a potential plant biostimulant 1831:1860 a potential plant biostimulant 1831:1860 Our findings revealed that TWDHLS could be used not only as a potential plant biostimulant but also as a better substitute for humic substances. 35426561 1 45 theme resources 256:264 arg1 supply 233:238 the short supply 223:238 the short supply of coal-related resources from which humic substances are extracted in large quantities for various applications 223:351 Emerging demand for humic substances escalated the short supply of coal-related resources from which humic substances are extracted in large quantities for various applications. 35426561 5 46 theme spectroscopic 823:835 arg1 properties 862:871 spectroscopic (13C CPMAS NMR and FTIR) properties 823:871 spectroscopic (13C CPMAS NMR and FTIR) properties 823:871 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 46 theme spectroscopic 823:835 arg1 FTIR 856:859 FTIR 856:859 FTIR 856:859 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 46 theme spectroscopic 823:835 arg1 NMR 848:850 13C CPMAS NMR 838:850 13C CPMAS NMR 838:850 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 7 47 theme stable 1287:1292 arg1 compounds 1294:1302 more stable compounds 1282:1302 more stable compounds 1282:1302 The presence of more stable compounds in TWDHLS contribute to its recalcitrant nature. 35426561 2 48 theme lignocellulosic 395:409 arg1 materials 417:425 lignocellulosic waste materials 395:425 lignocellulosic waste materials similar in structural and functional properties to humic substances 395:493 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 7 49 from presence 1270:1277 arg1 TWDHLS 1307:1312 TWDHLS 1307:1312 TWDHLS 1307:1312 The presence of more stable compounds in TWDHLS contribute to its recalcitrant nature. 35426561 6 50 contain have 1162:1165 arg1 both 1157:1160 both 1157:1160 both 1157:1160 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 6 50 contain have 1162:1165 arg2 distribution 1182:1193 similar carbon distribution 1167:1193 similar carbon distribution 1167:1193 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 4 51 contain has 723:725 arg1 other 717:721 other 717:721 other 717:721 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 4 51 contain has 723:725 arg2 acids 755:759 unpurified humic and fulvic acids 727:759 unpurified humic and fulvic acids called as humic-like substances (HLS) 727:797 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 0 52 link lignite-derived 68:82 arg1 substances 90:99 lignite-derived humic substances 68:99 lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity 68:173 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 10 53 theme plants 1687:1692 arg1 growth 1665:1670 the growth 1661:1670 the growth of tea nursery plants 1661:1692 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 0 54 with substances 52:61 arg1 substances 90:99 lignite-derived humic substances 68:99 lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity 68:173 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 8 55 from compounds 1432:1440 arg1 rich 1414:1417 rich 1414:1417 rich 1414:1417 NMR spectra of CHA significantly varied with TWDHLS and were rich in aliphatic compounds. 35426561 9 56 theme TWDHLS 1470:1475 arg1 activity 1458:1465 The biological activity 1443:1465 The biological activity of TWDHLS and CHA 1443:1483 The biological activity of TWDHLS and CHA was studied at five different concentrations (0, 20, 40, 80, and 160 mg L-1). 35426561 10 57 theme soil 1585:1588 arg1 TWDHLS 1602:1607 soil application TWDHLS 1585:1607 soil application TWDHLS at 80 mg L-1 concentration 1585:1634 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 5 58 theme Elemental 800:808 arg1 composition 810:820 Elemental composition 800:820 Elemental composition 800:820 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 1 59 theme humic 196:200 arg1 substances 202:211 humic substances 196:211 humic substances 196:211 Emerging demand for humic substances escalated the short supply of coal-related resources from which humic substances are extracted in large quantities for various applications. 35426561 2 60 from materials 417:425 arg1 Production 354:363 Production 354:363 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances 354:493 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 6 61 theme similar 1167:1173 arg1 distribution 1182:1193 similar carbon distribution 1167:1193 similar carbon distribution 1167:1193 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 0 62 theme spectroscopic 126:138 arg1 properties 140:149 spectroscopic properties 126:149 spectroscopic properties 126:149 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 5 63 theme humic-like 919:928 arg1 TWDHLS 942:947 TWDHLS 942:947 TWDHLS 942:947 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 63 theme humic-like 919:928 arg1 substances 930:939 tea waste derived humic-like substances 901:939 tea waste derived humic-like substances (TWDHLS) 901:948 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 4 64 theme humic-like 686:695 arg1 HLA 703:705 HLA 703:705 HLA 703:705 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 4 64 theme humic-like 686:695 arg1 acid 697:700 humic-like acid 686:700 purified humic-like acid (HLA) 677:706 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 10 65 theme 80 mg 1612:1616 arg1 concentration 1622:1634 80 mg L-1 concentration 1612:1634 80 mg L-1 concentration 1612:1634 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 10 66 theme nursery 1679:1685 arg1 plants 1687:1692 tea nursery plants 1675:1692 tea nursery plants 1675:1692 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 3 67 theme fractions 649:657 arg1 types 634:638 two types 630:638 extract two types of humic fractions 622:657 Tea waste is a by-product from tea manufacturing factories enriched in lignocellulose is used to extract two types of humic fractions. 35426561 1 68 theme short 227:231 arg1 supply 233:238 the short supply 223:238 the short supply of coal-related resources from which humic substances are extracted in large quantities for various applications 223:351 Emerging demand for humic substances escalated the short supply of coal-related resources from which humic substances are extracted in large quantities for various applications. 35426561 5 69 theme substances 930:939 arg1 properties 862:871 spectroscopic (13C CPMAS NMR and FTIR) properties 823:871 spectroscopic (13C CPMAS NMR and FTIR) properties 823:871 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 69 theme substances 930:939 arg1 NMR 848:850 13C CPMAS NMR 838:850 13C CPMAS NMR 838:850 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 69 theme substances 930:939 arg1 composition 810:820 Elemental composition 800:820 Elemental composition 800:820 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 69 theme substances 930:939 arg1 activity 889:896 biological activity 878:896 biological activity 878:896 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 69 theme substances 930:939 arg1 FTIR 856:859 FTIR 856:859 FTIR 856:859 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 6 70 theme lignin 1246:1251 arg1 derivatives 1253:1263 lignin derivatives 1246:1263 lignin derivatives 1246:1263 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 6 71 from derivatives 1253:1263 arg1 abundant 1203:1210 abundant 1203:1210 abundant 1203:1210 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 4 72 contain has 673:675 arg1 fraction 664:671 One fraction 660:671 One fraction 660:671 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 4 72 contain has 673:675 arg2 HLA 703:705 HLA 703:705 HLA 703:705 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 4 72 contain has 673:675 arg2 acid 697:700 humic-like acid 686:700 purified humic-like acid (HLA) 677:706 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 9 73 theme CHA 1481:1483 arg1 activity 1458:1465 The biological activity 1443:1465 The biological activity of TWDHLS and CHA 1443:1483 The biological activity of TWDHLS and CHA was studied at five different concentrations (0, 20, 40, 80, and 160 mg L-1). 35426561 5 74 theme tea 901:903 arg1 TWDHLS 942:947 TWDHLS 942:947 TWDHLS 942:947 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 74 theme tea 901:903 arg1 substances 930:939 tea waste derived humic-like substances 901:939 tea waste derived humic-like substances (TWDHLS) 901:948 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 0 75 theme humic 84:88 arg1 substances 90:99 lignite-derived humic substances 68:99 lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity 68:173 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 11 76 theme potential 1833:1841 arg1 TWDHLS 1798:1803 TWDHLS 1798:1803 TWDHLS 1798:1803 Our findings revealed that TWDHLS could be used not only as a potential plant biostimulant but also as a better substitute for humic substances. 35426561 11 76 theme potential 1833:1841 arg1 biostimulant 1849:1860 a potential plant biostimulant 1831:1860 a potential plant biostimulant 1831:1860 Our findings revealed that TWDHLS could be used not only as a potential plant biostimulant but also as a better substitute for humic substances. 35426561 5 77 theme derived 911:917 arg1 TWDHLS 942:947 TWDHLS 942:947 TWDHLS 942:947 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 77 theme derived 911:917 arg1 substances 930:939 tea waste derived humic-like substances 901:939 tea waste derived humic-like substances (TWDHLS) 901:948 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 4 78 theme unpurified 727:736 arg1 acids 755:759 unpurified humic and fulvic acids 727:759 unpurified humic and fulvic acids called as humic-like substances (HLS) 727:797 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 3 79 dep extract 622:628 arg1 types 634:638 two types 630:638 extract two types of humic fractions 622:657 Tea waste is a by-product from tea manufacturing factories enriched in lignocellulose is used to extract two types of humic fractions. 35426561 5 80 theme available 982:990 arg1 CHA 1004:1006 CHA 1004:1006 CHA 1004:1006 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 80 theme available 982:990 arg1 acid 998:1001 commercially available humic acid 969:1001 commercially available humic acid (CHA) extracted from lignite 969:1030 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 8 81 theme CHA 1368:1370 arg1 spectra 1357:1363 NMR spectra 1353:1363 NMR spectra of CHA 1353:1370 NMR spectra of CHA significantly varied with TWDHLS and were rich in aliphatic compounds. 35426561 6 82 from abundant 1203:1210 arg1 polysaccharides 1226:1240 cellulosic polysaccharides 1215:1240 cellulosic polysaccharides 1215:1240 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 6 82 from abundant 1203:1210 arg1 derivatives 1253:1263 lignin derivatives 1246:1263 lignin derivatives 1246:1263 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 2 83 theme structural 438:447 arg1 properties 464:473 structural and functional properties 438:473 structural and functional properties to humic substances 438:493 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 5 84 theme 13C 838:840 arg1 properties 862:871 spectroscopic (13C CPMAS NMR and FTIR) properties 823:871 spectroscopic (13C CPMAS NMR and FTIR) properties 823:871 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 84 theme 13C 838:840 arg1 NMR 848:850 13C CPMAS NMR 838:850 13C CPMAS NMR 838:850 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 2 85 theme similar 427:433 arg1 materials 417:425 lignocellulosic waste materials 395:425 lignocellulosic waste materials similar in structural and functional properties to humic substances 395:493 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 5 86 link derived 911:917 arg1 TWDHLS 942:947 TWDHLS 942:947 TWDHLS 942:947 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 5 86 link derived 911:917 arg1 substances 930:939 tea waste derived humic-like substances 901:939 tea waste derived humic-like substances (TWDHLS) 901:948 Elemental composition, spectroscopic (13C CPMAS NMR and FTIR) properties, and biological activity of tea waste derived humic-like substances (TWDHLS) were compared with commercially available humic acid (CHA) extracted from lignite. 35426561 7 87 theme recalcitrant 1332:1343 arg1 nature 1345:1350 its recalcitrant nature 1328:1350 its recalcitrant nature 1328:1350 The presence of more stable compounds in TWDHLS contribute to its recalcitrant nature. 35426561 11 88 theme humic 1898:1902 arg1 substances 1904:1913 humic substances 1898:1913 humic substances 1898:1913 Our findings revealed that TWDHLS could be used not only as a potential plant biostimulant but also as a better substitute for humic substances. 35426561 0 89 theme waste 27:31 arg1 study 14:18 A comparative study 0:18 A comparative study of tea waste 0:31 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 6 90 theme FTIR 1056:1059 arg1 characterization 1061:1076 FTIR characterization 1056:1076 FTIR characterization 1056:1076 Elemental analysis and FTIR characterization showed slight differences between HLA and HLS, while NMR results revealed that both have similar carbon distribution and are abundant in cellulosic polysaccharides and lignin derivatives. 35426561 2 91 theme functional 453:462 arg1 properties 464:473 structural and functional properties 438:473 structural and functional properties to humic substances 438:493 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 0 92 theme humic-like 41:50 arg1 substances 52:61 humic-like substances 41:61 humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity 41:173 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 1 93 theme various 332:338 arg1 applications 340:351 various applications 332:351 various applications 332:351 Emerging demand for humic substances escalated the short supply of coal-related resources from which humic substances are extracted in large quantities for various applications. 35426561 2 94 from similar 427:433 arg1 properties 464:473 structural and functional properties 438:473 structural and functional properties to humic substances 438:493 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 2 95 theme humic-like 368:377 arg1 substances 379:388 humic-like substances 368:388 humic-like substances 368:388 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 11 96 dep better 1876:1881 arg1 substitute 1883:1892 substitute 1883:1892 substitute for humic substances 1883:1913 Our findings revealed that TWDHLS could be used not only as a potential plant biostimulant but also as a better substitute for humic substances. 35426561 7 97 theme compounds 1294:1302 arg1 presence 1270:1277 The presence 1266:1277 The presence of more stable compounds in TWDHLS 1266:1312 The presence of more stable compounds in TWDHLS contribute to its recalcitrant nature. 35426561 2 98 theme waste 411:415 arg1 materials 417:425 lignocellulosic waste materials 395:425 lignocellulosic waste materials similar in structural and functional properties to humic substances 395:493 Production of humic-like substances from lignocellulosic waste materials similar in structural and functional properties to humic substances has gained interest recently. 35426561 1 99 theme coal-related 243:254 arg1 resources 256:264 coal-related resources 243:264 coal-related resources from which humic substances are extracted in large quantities for various applications 243:351 Emerging demand for humic substances escalated the short supply of coal-related resources from which humic substances are extracted in large quantities for various applications. 35426561 10 100 from results 1650:1656 arg1 growth 1665:1670 the growth 1661:1670 the growth of tea nursery plants 1661:1692 The results show that soil application TWDHLS at 80 mg L-1 concentration showed better results on the growth of tea nursery plants similar to CHA, contrasting to the variation in their structural properties. 35426561 4 101 theme purified 677:684 arg1 HLA 703:705 HLA 703:705 HLA 703:705 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 4 101 theme purified 677:684 arg1 acid 697:700 humic-like acid 686:700 purified humic-like acid (HLA) 677:706 One fraction has purified humic-like acid (HLA), and the other has unpurified humic and fulvic acids called as humic-like substances (HLS). 35426561 0 102 theme comparative 2:12 arg1 study 14:18 A comparative study 0:18 A comparative study of tea waste 0:31 A comparative study of tea waste derived humic-like substances with lignite-derived humic substances on chemical composition, spectroscopic properties and biological activity. 35426561 8 103 from rich 1414:1417 arg1 compounds 1432:1440 aliphatic compounds 1422:1440 aliphatic compounds 1422:1440 NMR spectra of CHA significantly varied with TWDHLS and were rich in aliphatic compounds. 37233678 6 0 theme enzymolysis 793:803 arg1 powder 813:818 enzymolysis seaweed powder 793:818 enzymolysis seaweed powder 793:818 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 11 1 theme seaweed 1866:1872 arg1 powder 1874:1879 enzymolysis seaweed powder 1854:1879 enzymolysis seaweed powder 1854:1879 Our findings provide new perspectives on the application of enzymolysis seaweed powder. 37233678 5 2 theme weight 625:630 arg1 kg 645:646 weight: 1.50 ± 0.29 kg 625:646 6 months; weight: 1.50 ± 0.29 kg 615:646 In total, 30 Ragdoll kittens (age: 6 months; weight: 1.50 ± 0.29 kg) were assigned to three treatment groups for a 4-week feeding trial. 37233678 8 3 theme SB 1461:1462 arg1 group 1464:1468 the SB group 1457:1468 the SB group 1457:1468 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 4 theme Desulfobacterota 1393:1408 arg1 lower 1474:1478 lower 1474:1478 lower 1474:1478 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 4 theme Desulfobacterota 1393:1408 arg1 abundance 1380:1388 the relative abundance 1367:1388 the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group 1367:1468 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 2 5 theme bioactive 287:295 arg1 substances 297:306 bioactive substances 287:306 bioactive substances 287:306 Seaweed is rich in plant polysaccharides and bioactive substances that are highly beneficial to gut health. 37233678 10 6 theme enzymolysis 1656:1666 arg1 powder 1676:1681 enzymolysis seaweed powder 1656:1681 enzymolysis seaweed powder 1656:1681 Conclusively, supplementing kitten diet with enzymolysis seaweed powder can promote intestinal health by enhancing the gut barrier function and optimizing the microbiota composition. 37233678 3 7 theme cat 385:387 arg1 health 393:398 cat gut health 385:398 cat gut health 385:398 However, the effects of seaweed on cat gut health have not been assessed. 37233678 1 8 theme health 176:181 arg1 problems 183:190 intestinal health problems 165:190 intestinal health problems 165:190 Kittens are prone to intestinal health problems as their intestines are not completely developed. 37233678 0 9 theme Saccharomyces 60:72 arg1 boulardii 74:82 Saccharomyces boulardii 60:82 Saccharomyces boulardii 60:82 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 6 10 theme dietary 721:727 arg1 treatment 729:737 The dietary treatment 717:737 The dietary treatment given 717:743 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 7 11 theme kittens 1182:1188 arg1 levels 1172:1177 the intestinal permeability and inflammation levels 1127:1177 the intestinal permeability and inflammation levels of kittens 1127:1188 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 8 12 theme SE 1497:1498 arg1 p 1507:1507 p ≤ 0.05 1507:1514 p ≤ 0.05 1507:1514 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 12 theme SE 1497:1498 arg1 group 1500:1504 the SE group 1493:1504 the SE group (p ≤ 0.05) 1493:1515 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 10 13 theme gut 1730:1732 arg1 function 1742:1749 the gut barrier function 1726:1749 the gut barrier function 1726:1749 Conclusively, supplementing kitten diet with enzymolysis seaweed powder can promote intestinal health by enhancing the gut barrier function and optimizing the microbiota composition. 37233678 8 14 theme relative 1371:1378 arg1 lower 1474:1478 lower 1474:1478 lower 1474:1478 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 14 theme relative 1371:1378 arg1 abundance 1380:1388 the relative abundance 1367:1388 the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group 1367:1468 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 15 from group 1296:1300 arg1 higher 1306:1311 higher 1306:1311 higher 1306:1311 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 15 from group 1296:1300 arg1 abundance 1204:1212 The relative abundance 1191:1212 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group 1191:1300 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 16 theme Prevotellaceae 1249:1262 arg1 higher 1306:1311 higher 1306:1311 higher 1306:1311 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 16 theme Prevotellaceae 1249:1262 arg1 abundance 1204:1212 The relative abundance 1191:1212 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group 1191:1300 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 17 theme ≤ 1509:1509 arg1 p 1507:1507 p ≤ 0.05 1507:1514 p ≤ 0.05 1507:1514 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 17 theme ≤ 1509:1509 arg1 group 1500:1504 the SE group 1493:1504 the SE group (p ≤ 0.05) 1493:1515 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 7 18 theme intestinal 1131:1140 arg1 permeability 1142:1153 intestinal permeability 1131:1153 intestinal permeability 1131:1153 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 11 19 from perspectives 1819:1830 arg1 application 1839:1849 the application 1835:1849 the application of enzymolysis seaweed powder 1835:1879 Our findings provide new perspectives on the application of enzymolysis seaweed powder. 37233678 9 20 from level 1573:1577 arg1 kittens 1602:1608 kittens 1602:1608 kittens 1602:1608 Moreover, enzymolysis seaweed powder did not alter the level of intestinal SCFAs in kittens. 37233678 2 21 from substances 297:306 arg1 rich 253:256 rich 253:256 rich 253:256 Seaweed is rich in plant polysaccharides and bioactive substances that are highly beneficial to gut health. 37233678 5 22 theme feeding 702:708 arg1 trial 710:714 a 4-week feeding trial 693:714 a 4-week feeding trial 693:714 In total, 30 Ragdoll kittens (age: 6 months; weight: 1.50 ± 0.29 kg) were assigned to three treatment groups for a 4-week feeding trial. 37233678 4 23 theme enzymolysis 488:498 arg1 powder 508:513 enzymolysis seaweed powder 488:513 enzymolysis seaweed powder 488:513 This study compared the effects of dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii on the intestinal health of kittens. 37233678 0 24 theme boulardii 74:82 arg1 Effects 18:24 the Effects 14:24 the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens 14:141 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 0 25 from Comparison 0:9 arg1 Health 98:103 Intestinal Health 87:103 Intestinal Health 87:103 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 0 25 from Comparison 0:9 arg1 Composition 120:130 Microbiota Composition 109:130 Microbiota Composition 109:130 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 10 26 theme microbiota 1770:1779 arg1 composition 1781:1791 the microbiota composition 1766:1791 the microbiota composition 1766:1791 Conclusively, supplementing kitten diet with enzymolysis seaweed powder can promote intestinal health by enhancing the gut barrier function and optimizing the microbiota composition. 37233678 0 27 theme Intestinal 87:96 arg1 Health 98:103 Intestinal Health 87:103 Intestinal Health 87:103 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 8 28 theme CON 1331:1333 arg1 p 1350:1350 p ≤ 0.05 1350:1357 p ≤ 0.05 1350:1357 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 28 theme CON 1331:1333 arg1 groups 1342:1347 the CON and SB groups 1327:1347 groups 1342:1347 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 4 29 theme supplementation 467:481 arg1 effects 448:454 the effects 444:454 the effects of dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii on the intestinal health of kittens 444:577 This study compared the effects of dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii on the intestinal health of kittens. 37233678 5 30 theme 4-week 695:700 arg1 trial 710:714 a 4-week feeding trial 693:714 a 4-week feeding trial 693:714 In total, 30 Ragdoll kittens (age: 6 months; weight: 1.50 ± 0.29 kg) were assigned to three treatment groups for a 4-week feeding trial. 37233678 2 31 from rich 253:256 arg1 polysaccharides 267:281 plant polysaccharides 261:281 plant polysaccharides 261:281 Seaweed is rich in plant polysaccharides and bioactive substances that are highly beneficial to gut health. 37233678 2 31 from rich 253:256 arg1 substances 297:306 bioactive substances 287:306 bioactive substances 287:306 Seaweed is rich in plant polysaccharides and bioactive substances that are highly beneficial to gut health. 37233678 9 32 theme seaweed 1540:1546 arg1 powder 1548:1553 enzymolysis seaweed powder 1528:1553 enzymolysis seaweed powder 1528:1553 Moreover, enzymolysis seaweed powder did not alter the level of intestinal SCFAs in kittens. 37233678 4 33 theme intestinal 550:559 arg1 health 561:566 the intestinal health 546:566 the intestinal health of kittens 546:577 This study compared the effects of dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii on the intestinal health of kittens. 37233678 6 34 dep boulardii 899:907 arg1 CFU/kg 919:924 2 × 1010 CFU/kg 910:924 2 × 1010 CFU/kg of feed 910:932 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 8 35 theme SB 1339:1340 arg1 p 1350:1350 p ≤ 0.05 1350:1357 p ≤ 0.05 1350:1357 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 35 theme SB 1339:1340 arg1 groups 1342:1347 the CON and SB groups 1327:1347 groups 1342:1347 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 5 36 dep age 610:612 arg1 months 617:622 6 months 615:622 6 months; weight: 1.50 ± 0.29 kg 615:646 In total, 30 Ragdoll kittens (age: 6 months; weight: 1.50 ± 0.29 kg) were assigned to three treatment groups for a 4-week feeding trial. 37233678 6 37 dep diet 771:774 arg1 powder 813:818 enzymolysis seaweed powder 793:818 enzymolysis seaweed powder 793:818 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 6 37 dep diet 771:774 arg1 g/kg 824:827 20 g/kg 821:827 (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) 761:836 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 6 37 dep diet 771:774 arg1 1 762:762 1 762:762 1 762:762 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 6 37 dep diet 771:774 arg1 CON 787:789 (2) CON 783:789 (2) CON 783:789 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 8 38 theme relative 1195:1202 arg1 higher 1306:1311 higher 1306:1311 higher 1306:1311 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 38 theme relative 1195:1202 arg1 abundance 1204:1212 The relative abundance 1191:1212 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group 1191:1300 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 0 39 theme Seaweed 41:47 arg1 Powder 49:54 Enzymolysis Seaweed Powder 29:54 Enzymolysis Seaweed Powder 29:54 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 0 40 from Effects 18:24 arg1 Health 98:103 Intestinal Health 87:103 Intestinal Health 87:103 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 0 40 from Effects 18:24 arg1 Composition 120:130 Microbiota Composition 109:130 Microbiota Composition 109:130 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 6 41 theme basal 765:769 arg1 CON 777:779 CON 777:779 CON 777:779 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 6 41 theme basal 765:769 arg1 diet 771:774 (1) basal diet 761:774 (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) 761:836 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 6 42 theme feed 929:932 arg1 CFU/kg 919:924 2 × 1010 CFU/kg 910:924 2 × 1010 CFU/kg of feed 910:932 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 5 43 dep kittens 601:607 arg1 age 610:612 age 610:612 age 610:612 In total, 30 Ragdoll kittens (age: 6 months; weight: 1.50 ± 0.29 kg) were assigned to three treatment groups for a 4-week feeding trial. 37233678 8 44 theme ≤ 1352:1352 arg1 p 1350:1350 p ≤ 0.05 1350:1357 p ≤ 0.05 1350:1357 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 44 theme ≤ 1352:1352 arg1 groups 1342:1347 the CON and SB groups 1327:1347 groups 1342:1347 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 2 45 theme gut 338:340 arg1 health 342:347 gut health 338:347 gut health 338:347 Seaweed is rich in plant polysaccharides and bioactive substances that are highly beneficial to gut health. 37233678 7 46 theme enzymolysis 1038:1048 arg1 powder 1058:1063 the enzymolysis seaweed powder 1034:1063 the enzymolysis seaweed powder 1034:1063 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 9 47 theme intestinal 1582:1591 arg1 SCFAs 1593:1597 intestinal SCFAs 1582:1597 intestinal SCFAs 1582:1597 Moreover, enzymolysis seaweed powder did not alter the level of intestinal SCFAs in kittens. 37233678 3 48 theme gut 389:391 arg1 health 393:398 cat gut health 385:398 cat gut health 385:398 However, the effects of seaweed on cat gut health have not been assessed. 37233678 6 49 theme seaweed 805:811 arg1 powder 813:818 enzymolysis seaweed powder 793:818 enzymolysis seaweed powder 793:818 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 6 50 theme × 912:912 arg1 CFU/kg 919:924 2 × 1010 CFU/kg 910:924 2 × 1010 CFU/kg of feed 910:932 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 0 51 from Composition 120:130 arg1 Kittens 135:141 Kittens 135:141 Kittens 135:141 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 0 51 from Composition 120:130 arg1 Comparison 0:9 Comparison 0:9 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 0:142 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 8 52 theme Erysipelatoclostridium 1431:1452 arg1 lower 1474:1478 lower 1474:1478 lower 1474:1478 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 52 theme Erysipelatoclostridium 1431:1452 arg1 abundance 1380:1388 the relative abundance 1367:1388 the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group 1367:1468 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 53 theme SE 1293:1294 arg1 group 1296:1300 the SE group 1289:1300 the SE group 1289:1300 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 11 54 theme powder 1874:1879 arg1 application 1839:1849 the application 1835:1849 the application of enzymolysis seaweed powder 1835:1879 Our findings provide new perspectives on the application of enzymolysis seaweed powder. 37233678 7 55 theme dietary 1005:1011 arg1 supplementation 1013:1027 dietary supplementation 1005:1027 dietary supplementation with the enzymolysis seaweed powder 1005:1063 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 6 56 dep CON 787:789 arg1 2 784:784 2 784:784 2 784:784 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 7 57 with supplementation 1013:1027 arg1 powder 1058:1063 the enzymolysis seaweed powder 1034:1063 the enzymolysis seaweed powder 1034:1063 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 11 58 theme enzymolysis 1854:1864 arg1 powder 1874:1879 enzymolysis seaweed powder 1854:1879 enzymolysis seaweed powder 1854:1879 Our findings provide new perspectives on the application of enzymolysis seaweed powder. 37233678 10 59 theme seaweed 1668:1674 arg1 powder 1676:1681 enzymolysis seaweed powder 1656:1681 enzymolysis seaweed powder 1656:1681 Conclusively, supplementing kitten diet with enzymolysis seaweed powder can promote intestinal health by enhancing the gut barrier function and optimizing the microbiota composition. 37233678 1 60 theme intestinal 165:174 arg1 problems 183:190 intestinal health problems 165:190 intestinal health problems 165:190 Kittens are prone to intestinal health problems as their intestines are not completely developed. 37233678 10 61 theme intestinal 1695:1704 arg1 health 1706:1711 intestinal health 1695:1711 intestinal health 1695:1711 Conclusively, supplementing kitten diet with enzymolysis seaweed powder can promote intestinal health by enhancing the gut barrier function and optimizing the microbiota composition. 37233678 4 62 from effects 448:454 arg1 health 561:566 the intestinal health 546:566 the intestinal health of kittens 546:577 This study compared the effects of dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii on the intestinal health of kittens. 37233678 6 63 theme feed 832:835 arg1 CON 777:779 CON 777:779 CON 777:779 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 6 63 theme feed 832:835 arg1 diet 771:774 (1) basal diet 761:774 (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) 761:836 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 11 64 theme new 1815:1817 arg1 perspectives 1819:1830 new perspectives 1815:1830 new perspectives on the application of enzymolysis seaweed powder 1815:1879 Our findings provide new perspectives on the application of enzymolysis seaweed powder. 37233678 8 65 from abundance 1204:1212 arg1 group 1296:1300 the SE group 1289:1300 the SE group 1289:1300 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 5 66 theme ± 638:638 arg1 kg 645:646 weight: 1.50 ± 0.29 kg 625:646 6 months; weight: 1.50 ± 0.29 kg 615:646 In total, 30 Ragdoll kittens (age: 6 months; weight: 1.50 ± 0.29 kg) were assigned to three treatment groups for a 4-week feeding trial. 37233678 3 67 from effects 363:369 arg1 health 393:398 cat gut health 385:398 cat gut health 385:398 However, the effects of seaweed on cat gut health have not been assessed. 37233678 8 68 theme Faecalibacterium 1269:1284 arg1 higher 1306:1311 higher 1306:1311 higher 1306:1311 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 68 theme Faecalibacterium 1269:1284 arg1 abundance 1204:1212 The relative abundance 1191:1212 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group 1191:1300 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 7 69 theme inflammation 1159:1170 arg1 levels 1172:1177 the intestinal permeability and inflammation levels 1127:1177 the intestinal permeability and inflammation levels of kittens 1127:1188 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 8 70 from abundance 1380:1388 arg1 group 1464:1468 the SB group 1457:1468 the SB group 1457:1468 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 2 71 theme plant 261:265 arg1 polysaccharides 267:281 plant polysaccharides 261:281 plant polysaccharides 261:281 Seaweed is rich in plant polysaccharides and bioactive substances that are highly beneficial to gut health. 37233678 2 72 from polysaccharides 267:281 arg1 rich 253:256 rich 253:256 rich 253:256 Seaweed is rich in plant polysaccharides and bioactive substances that are highly beneficial to gut health. 37233678 0 73 from Health 98:103 arg1 Kittens 135:141 Kittens 135:141 Kittens 135:141 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 0 73 from Health 98:103 arg1 Comparison 0:9 Comparison 0:9 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 0:142 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 7 74 theme permeability 1142:1153 arg1 levels 1172:1177 the intestinal permeability and inflammation levels 1127:1177 the intestinal permeability and inflammation levels of kittens 1127:1188 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 7 75 theme SB 994:995 arg1 groups 997:1002 the CON and SB groups 982:1002 groups 997:1002 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 4 76 theme seaweed 500:506 arg1 powder 508:513 enzymolysis seaweed powder 488:513 enzymolysis seaweed powder 488:513 This study compared the effects of dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii on the intestinal health of kittens. 37233678 10 77 theme barrier 1734:1740 arg1 function 1742:1749 the gut barrier function 1726:1749 the gut barrier function 1726:1749 Conclusively, supplementing kitten diet with enzymolysis seaweed powder can promote intestinal health by enhancing the gut barrier function and optimizing the microbiota composition. 37233678 7 78 theme CON 986:988 arg1 groups 997:1002 the CON and SB groups 982:1002 groups 997:1002 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 5 79 theme treatment 672:680 arg1 groups 682:687 three treatment groups 666:687 three treatment groups for a 4-week feeding trial 666:714 In total, 30 Ragdoll kittens (age: 6 months; weight: 1.50 ± 0.29 kg) were assigned to three treatment groups for a 4-week feeding trial. 37233678 5 80 theme Ragdoll 593:599 arg1 kittens 601:607 30 Ragdoll kittens 590:607 30 Ragdoll kittens (age: 6 months; weight: 1.50 ± 0.29 kg) 590:647 In total, 30 Ragdoll kittens (age: 6 months; weight: 1.50 ± 0.29 kg) were assigned to three treatment groups for a 4-week feeding trial. 37233678 4 81 theme dietary 459:465 arg1 supplementation 467:481 dietary supplementation 459:481 dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii 459:541 This study compared the effects of dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii on the intestinal health of kittens. 37233678 0 82 theme Microbiota 109:118 arg1 Composition 120:130 Microbiota Composition 109:130 Microbiota Composition 109:130 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 7 83 theme antioxidant 1089:1099 arg1 capacity 1101:1108 the immune and antioxidant capacity 1074:1108 the immune and antioxidant capacity 1074:1108 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 9 84 theme enzymolysis 1528:1538 arg1 powder 1548:1553 enzymolysis seaweed powder 1528:1553 enzymolysis seaweed powder 1528:1553 Moreover, enzymolysis seaweed powder did not alter the level of intestinal SCFAs in kittens. 37233678 6 85 dep CON 879:881 arg1 3 876:876 3 876:876 3 876:876 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 0 86 theme Effects 18:24 arg1 Comparison 0:9 Comparison 0:9 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 0:142 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 7 87 theme immune 1078:1083 arg1 capacity 1101:1108 the immune and antioxidant capacity 1074:1108 the immune and antioxidant capacity 1074:1108 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 3 88 theme seaweed 374:380 arg1 effects 363:369 the effects 359:369 the effects of seaweed on cat gut health 359:398 However, the effects of seaweed on cat gut health have not been assessed. 37233678 4 89 theme kittens 571:577 arg1 health 561:566 the intestinal health 546:566 the intestinal health of kittens 546:577 This study compared the effects of dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii on the intestinal health of kittens. 37233678 0 90 theme Enzymolysis 29:39 arg1 Powder 49:54 Enzymolysis Seaweed Powder 29:54 Enzymolysis Seaweed Powder 29:54 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 9 91 theme SCFAs 1593:1597 arg1 level 1573:1577 the level 1569:1577 the level of intestinal SCFAs in kittens 1569:1608 Moreover, enzymolysis seaweed powder did not alter the level of intestinal SCFAs in kittens. 37233678 5 92 dep months 617:622 arg1 kg 645:646 weight: 1.50 ± 0.29 kg 625:646 6 months; weight: 1.50 ± 0.29 kg 615:646 In total, 30 Ragdoll kittens (age: 6 months; weight: 1.50 ± 0.29 kg) were assigned to three treatment groups for a 4-week feeding trial. 37233678 0 93 theme Powder 49:54 arg1 Effects 18:24 the Effects 14:24 the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens 14:141 Comparison of the Effects of Enzymolysis Seaweed Powder and Saccharomyces boulardii on Intestinal Health and Microbiota Composition in Kittens. 37233678 8 94 dep Prevotellaceae 1249:1262 arg1 Bacteroidetes 1217:1229 Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium 1217:1284 Bacteroidetes 1217:1229 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 7 95 theme seaweed 1050:1056 arg1 powder 1058:1063 the enzymolysis seaweed powder 1034:1063 the enzymolysis seaweed powder 1034:1063 Compared with the CON and SB groups, dietary supplementation with the enzymolysis seaweed powder improved the immune and antioxidant capacity and also reduced the intestinal permeability and inflammation levels of kittens. 37233678 8 96 theme Sutterellaceae 1411:1424 arg1 lower 1474:1478 lower 1474:1478 lower 1474:1478 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 8 96 theme Sutterellaceae 1411:1424 arg1 abundance 1380:1388 the relative abundance 1367:1388 the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group 1367:1468 The relative abundance of Bacteroidetes, Lachnospiraceae, Prevotellaceae, and Faecalibacterium in the SE group was higher than those in the CON and SB groups (p ≤ 0.05), while the relative abundance of Desulfobacterota, Sutterellaceae, and Erysipelatoclostridium in the SB group was lower than that in the SE group (p ≤ 0.05). 37233678 6 97 theme Saccharomyces 885:897 arg1 boulardii 899:907 Saccharomyces boulardii 885:907 Saccharomyces boulardii (2 × 1010 CFU/kg of feed) 885:933 The dietary treatment given was as follows: (1) basal diet (CON); (2) CON + enzymolysis seaweed powder (20 g/kg of feed) mixed evenly with the diet (SE); and (3) CON + Saccharomyces boulardii (2 × 1010 CFU/kg of feed) mixed evenly with the diet (SB). 37233678 4 98 with supplementation 467:481 arg1 powder 508:513 enzymolysis seaweed powder 488:513 enzymolysis seaweed powder 488:513 This study compared the effects of dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii on the intestinal health of kittens. 37233678 4 98 with supplementation 467:481 arg1 boulardii 533:541 Saccharomyces boulardii 519:541 Saccharomyces boulardii 519:541 This study compared the effects of dietary supplementation with enzymolysis seaweed powder and Saccharomyces boulardii on the intestinal health of kittens. 36713189 3 0 from dysbiosis 720:728 arg1 mice 733:736 mice 733:736 mice 733:736 Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. 36713189 6 1 from decrease 1215:1222 arg1 abundances 1231:1240 the abundances 1227:1240 the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) 1227:1335 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 1 from decrease 1215:1222 arg1 contents 1360:1367 the contents 1356:1367 the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.) 1356:1437 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 2 2 theme oxidative 413:421 arg1 stress 423:428 oxidative stress 413:428 oxidative stress 413:428 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 1 3 theme host 289:292 arg1 health 294:299 the host health 285:299 the host health 285:299 Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. 36713189 0 4 theme gut 105:107 arg1 microbiota 109:118 gut microbiota 105:118 gut microbiota 105:118 Radix paeoniae alba polysaccharide attenuates lipopolysaccharide-induced intestinal injury by regulating gut microbiota. 36713189 9 5 dep popularization 1782:1795 arg1 the 1778:1780 the 1778:1780 the 1778:1780 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 7 6 theme bacteria 1582:1589 arg1 abundance 1564:1572 the abundance 1560:1572 the abundance of some bacteria 1560:1589 However, RPAP administration, especially in high doses, could improve the composition of the gut microbiota by altering the abundance of some bacteria. 36713189 5 7 theme LPS 991:993 arg1 exposure 995:1002 LPS exposure 991:1002 LPS exposure 991:1002 Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. 36713189 9 8 theme microbiota 1882:1891 arg1 perspective 1863:1873 the perspective 1859:1873 the perspective of gut microbiota 1859:1891 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 8 9 theme RPAP 1637:1640 arg1 administration 1642:1655 RPAP administration 1637:1655 RPAP administration 1637:1655 Taken together, this study demonstrated that RPAP administration could ameliorate LPS-induced intestinal injury by regulating gut microbiota. 36713189 4 10 theme intestinal 817:826 arg1 damage 828:833 LPS-induced intestinal damage 805:833 LPS-induced intestinal damage 805:833 Results indicated that RPAP administration effectively alleviated LPS-induced intestinal damage in dose dependent. 36713189 6 11 dep bacteria 1383:1390 arg1 Enterococcus 1419:1430 Enterococcus 1419:1430 Enterococcus 1419:1430 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 11 dep bacteria 1383:1390 arg1 Helicobacter 1405:1416 Helicobacter 1405:1416 Helicobacter 1405:1416 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 11 dep bacteria 1383:1390 arg1 etc 1433:1435 etc 1433:1435 etc 1433:1435 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 12 dep resulted 1130:1137 arg1 characterized 1196:1208 characterized 1196:1208 characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.) 1196:1437 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 13 theme bacteria 1383:1390 arg1 contents 1360:1367 the contents 1356:1367 the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.) 1356:1437 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 2 14 from effects 402:408 arg1 host 437:440 the host 433:440 the host 433:440 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 2 15 theme plant-derived 322:334 arg1 polysaccharides 336:350 multiple plant-derived polysaccharides 313:350 multiple plant-derived polysaccharides 313:350 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 9 16 theme gut 1878:1880 arg1 microbiota 1882:1891 gut microbiota 1878:1891 gut microbiota 1878:1891 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 5 17 theme significant 933:943 arg1 decrease 945:952 the significant decrease 929:952 the significant decrease in gut microbial diversity caused by LPS exposure 929:1002 Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. 36713189 3 18 from injury 695:700 arg1 mice 733:736 mice 733:736 mice 733:736 Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. 36713189 6 19 theme beneficial 1245:1254 arg1 bacteria 1256:1263 beneficial bacteria 1245:1263 beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) 1245:1335 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 2 20 dep radix 482:486 arg1 paeoniae 488:495 paeoniae 488:495 paeoniae 488:495 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 2 21 theme protective 461:470 arg1 effect 472:477 the potential protective effect 447:477 the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host 447:530 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 2 22 theme multiple 313:320 arg1 polysaccharides 336:350 multiple plant-derived polysaccharides 313:350 multiple plant-derived polysaccharides 313:350 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 0 23 theme intestinal 73:82 arg1 injury 84:89 lipopolysaccharide-induced intestinal injury 46:89 lipopolysaccharide-induced intestinal injury 46:89 Radix paeoniae alba polysaccharide attenuates lipopolysaccharide-induced intestinal injury by regulating gut microbiota. 36713189 7 24 theme gut 1533:1535 arg1 microbiota 1537:1546 the gut microbiota 1529:1546 the gut microbiota 1529:1546 However, RPAP administration, especially in high doses, could improve the composition of the gut microbiota by altering the abundance of some bacteria. 36713189 6 25 theme LPS 1117:1119 arg1 exposure 1121:1128 LPS exposure 1117:1128 LPS exposure 1117:1128 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 2 26 theme alba 497:500 arg1 RPAP 518:521 RPAP 518:521 RPAP 518:521 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 2 26 theme alba 497:500 arg1 polysaccharide 502:515 radix paeoniae alba polysaccharide 482:515 radix paeoniae alba polysaccharide (RPAP) 482:522 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 5 27 theme gut 957:959 arg1 diversity 971:979 gut microbial diversity 957:979 gut microbial diversity 957:979 Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. 36713189 0 28 theme paeoniae 6:13 arg1 polysaccharide 20:33 Radix paeoniae alba polysaccharide 0:33 Radix paeoniae alba polysaccharide 0:33 Radix paeoniae alba polysaccharide attenuates lipopolysaccharide-induced intestinal injury by regulating gut microbiota. 36713189 7 29 theme microbiota 1537:1546 arg1 composition 1514:1524 the composition 1510:1524 the composition of the gut microbiota 1510:1546 However, RPAP administration, especially in high doses, could improve the composition of the gut microbiota by altering the abundance of some bacteria. 36713189 6 30 from changes 1154:1160 arg1 composition 1183:1193 the gut microbial composition 1165:1193 the gut microbial composition 1165:1193 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 4 31 theme LPS-induced 805:815 arg1 damage 828:833 LPS-induced intestinal damage 805:833 LPS-induced intestinal damage 805:833 Results indicated that RPAP administration effectively alleviated LPS-induced intestinal damage in dose dependent. 36713189 7 32 from administration 1454:1467 arg1 doses 1489:1493 high doses 1484:1493 high doses 1484:1493 However, RPAP administration, especially in high doses, could improve the composition of the gut microbiota by altering the abundance of some bacteria. 36713189 5 33 theme microbial 961:969 arg1 diversity 971:979 gut microbial diversity 957:979 gut microbial diversity 957:979 Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. 36713189 0 34 theme Radix 0:4 arg1 polysaccharide 20:33 Radix paeoniae alba polysaccharide 0:33 Radix paeoniae alba polysaccharide 0:33 Radix paeoniae alba polysaccharide attenuates lipopolysaccharide-induced intestinal injury by regulating gut microbiota. 36713189 6 35 theme pathogenic 1372:1381 arg1 bacteria 1383:1390 pathogenic bacteria 1372:1390 pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.) 1372:1437 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 3 36 theme microbial 710:718 arg1 dysbiosis 720:728 gut microbial dysbiosis 706:728 gut microbial dysbiosis 706:728 Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. 36713189 1 37 theme Accumulating 121:132 arg1 evidence 134:141 Accumulating evidence 121:141 Accumulating evidence 121:141 Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. 36713189 9 38 from perspective 1863:1873 arg1 application 1801:1811 application 1801:1811 application 1801:1811 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 9 38 from perspective 1863:1873 arg1 popularization 1782:1795 popularization 1782:1795 popularization 1782:1795 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 6 39 theme microbial 1173:1181 arg1 composition 1183:1193 the gut microbial composition 1165:1193 the gut microbial composition 1165:1193 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 2 40 theme radix 482:486 arg1 RPAP 518:521 RPAP 518:521 RPAP 518:521 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 2 40 theme radix 482:486 arg1 polysaccharide 502:515 radix paeoniae alba polysaccharide 482:515 radix paeoniae alba polysaccharide (RPAP) 482:522 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 6 41 theme taxonomic 1073:1081 arg1 investigation 1083:1095 Microbial taxonomic investigation 1063:1095 Microbial taxonomic investigation 1063:1095 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 5 42 theme normal 1048:1053 arg1 levels 1055:1060 normal levels 1048:1060 normal levels 1048:1060 Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. 36713189 1 43 theme multiple 233:240 arg1 diseases 250:257 multiple chronic diseases 233:257 multiple chronic diseases 233:257 Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. 36713189 0 44 theme alba 15:18 arg1 polysaccharide 20:33 Radix paeoniae alba polysaccharide 0:33 Radix paeoniae alba polysaccharide 0:33 Radix paeoniae alba polysaccharide attenuates lipopolysaccharide-induced intestinal injury by regulating gut microbiota. 36713189 6 45 theme Microbial 1063:1071 arg1 investigation 1083:1095 Microbial taxonomic investigation 1063:1095 Microbial taxonomic investigation 1063:1095 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 3 46 theme different 596:604 arg1 doses 606:610 different doses 596:610 different doses of RPAP administration 596:633 Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. 36713189 1 47 theme chronic 242:248 arg1 diseases 250:257 multiple chronic diseases 233:257 multiple chronic diseases 233:257 Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. 36713189 0 48 theme lipopolysaccharide-induced 46:71 arg1 injury 84:89 lipopolysaccharide-induced intestinal injury 46:89 lipopolysaccharide-induced intestinal injury 46:89 Radix paeoniae alba polysaccharide attenuates lipopolysaccharide-induced intestinal injury by regulating gut microbiota. 36713189 2 49 link plant-derived 322:334 arg1 polysaccharides 336:350 multiple plant-derived polysaccharides 313:350 multiple plant-derived polysaccharides 313:350 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 9 50 theme RPAP 1816:1819 arg1 application 1801:1811 application 1801:1811 application 1801:1811 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 9 50 theme RPAP 1816:1819 arg1 popularization 1782:1795 popularization 1782:1795 popularization 1782:1795 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 1 51 theme diseases 250:257 arg1 progression 218:228 the progression 214:228 the progression of multiple chronic diseases, which seriously threaten the host health 214:299 Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. 36713189 1 51 theme diseases 250:257 arg1 inflammation 197:208 inflammation 197:208 inflammation 197:208 Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. 36713189 2 52 theme potential 451:459 arg1 effect 472:477 the potential protective effect 447:477 the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host 447:530 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 8 53 theme LPS-induced 1674:1684 arg1 injury 1697:1702 LPS-induced intestinal injury 1674:1702 LPS-induced intestinal injury 1674:1702 Taken together, this study demonstrated that RPAP administration could ameliorate LPS-induced intestinal injury by regulating gut microbiota. 36713189 3 54 theme -induced 675:682 arg1 injury 695:700 lipopolysaccharide (LPS)-induced intestinal injury 651:700 lipopolysaccharide (LPS)-induced intestinal injury 651:700 Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. 36713189 5 55 theme RPAP 900:903 arg1 administration 905:918 RPAP administration 900:918 RPAP administration 900:918 Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. 36713189 6 56 dep bacteria 1256:1263 arg1 etc. 1331:1334 etc. 1331:1334 etc. 1331:1334 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 56 dep bacteria 1256:1263 arg1 Rikenellaceae_RC9_gut_group 1302:1328 Rikenellaceae_RC9_gut_group 1302:1328 Rikenellaceae_RC9_gut_group 1302:1328 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 56 dep bacteria 1256:1263 arg1 Alistipes 1281:1289 Alistipes 1281:1289 Alistipes 1281:1289 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 5 57 theme amplicon 868:875 arg1 sequencing 877:886 amplicon sequencing 868:886 amplicon sequencing 868:886 Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. 36713189 9 58 theme alleviating 1825:1835 arg1 stress 1847:1852 alleviating oxidative stress 1825:1852 alleviating oxidative stress 1825:1852 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 3 59 theme intestinal 684:693 arg1 injury 695:700 lipopolysaccharide (LPS)-induced intestinal injury 651:700 lipopolysaccharide (LPS)-induced intestinal injury 651:700 Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. 36713189 3 60 theme RPAP 615:618 arg1 administration 620:633 RPAP administration 615:633 RPAP administration 615:633 Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. 36713189 5 61 from decrease 945:952 arg1 diversity 971:979 gut microbial diversity 957:979 gut microbial diversity 957:979 Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. 36713189 4 62 theme RPAP 762:765 arg1 administration 767:780 RPAP administration 762:780 RPAP administration 762:780 Results indicated that RPAP administration effectively alleviated LPS-induced intestinal damage in dose dependent. 36713189 2 63 theme polysaccharide 502:515 arg1 effect 472:477 the potential protective effect 447:477 the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host 447:530 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 9 64 theme oxidative 1837:1845 arg1 stress 1847:1852 alleviating oxidative stress 1825:1852 alleviating oxidative stress 1825:1852 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 3 65 theme administration 620:633 arg1 doses 606:610 different doses 596:610 different doses of RPAP administration 596:633 Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. 36713189 1 66 theme oxidative 158:166 arg1 stress 168:173 oxidative stress 158:173 oxidative stress 158:173 Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. 36713189 8 67 theme intestinal 1686:1695 arg1 injury 1697:1702 LPS-induced intestinal injury 1674:1702 LPS-induced intestinal injury 1674:1702 Taken together, this study demonstrated that RPAP administration could ameliorate LPS-induced intestinal injury by regulating gut microbiota. 36713189 9 68 theme stress 1847:1852 arg1 application 1801:1811 application 1801:1811 application 1801:1811 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 9 68 theme stress 1847:1852 arg1 popularization 1782:1795 popularization 1782:1795 popularization 1782:1795 Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota. 36713189 7 69 theme RPAP 1449:1452 arg1 administration 1454:1467 RPAP administration 1449:1467 RPAP administration 1449:1467 However, RPAP administration, especially in high doses, could improve the composition of the gut microbiota by altering the abundance of some bacteria. 36713189 7 70 theme high 1484:1487 arg1 doses 1489:1493 high doses 1484:1493 high doses 1484:1493 However, RPAP administration, especially in high doses, could improve the composition of the gut microbiota by altering the abundance of some bacteria. 36713189 6 71 theme significant 1142:1152 arg1 changes 1154:1160 significant changes 1142:1160 significant changes in the gut microbial composition 1142:1193 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 72 dep Alistipes 1281:1289 arg1 Bacillus 1292:1299 Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc. 1266:1334 Bacillus 1292:1299 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 3 73 theme gut 706:708 arg1 dysbiosis 720:728 gut microbial dysbiosis 706:728 gut microbial dysbiosis 706:728 Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. 36713189 5 74 theme alpha-diversity 1021:1035 arg1 indices 1037:1043 the alpha-diversity indices 1017:1043 the alpha-diversity indices 1017:1043 Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. 36713189 2 75 theme negative 393:400 arg1 effects 402:408 the negative effects 389:408 the negative effects of oxidative stress on the host 389:440 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 6 76 theme gut 1169:1171 arg1 composition 1183:1193 the gut microbial composition 1165:1193 the gut microbial composition 1165:1193 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 77 from increase 1344:1351 arg1 abundances 1231:1240 the abundances 1227:1240 the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) 1227:1335 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 77 from increase 1344:1351 arg1 contents 1360:1367 the contents 1356:1367 the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.) 1356:1437 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 6 78 theme bacteria 1256:1263 arg1 abundances 1231:1240 the abundances 1227:1240 the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) 1227:1335 Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). 36713189 2 79 from effect 472:477 arg1 host 527:530 host 527:530 host 527:530 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 2 80 theme stress 423:428 arg1 effects 402:408 the negative effects 389:408 the negative effects of oxidative stress on the host 389:440 Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. 36713189 8 81 theme gut 1718:1720 arg1 microbiota 1722:1731 gut microbiota 1718:1731 gut microbiota 1718:1731 Taken together, this study demonstrated that RPAP administration could ameliorate LPS-induced intestinal injury by regulating gut microbiota. 35452093 0 0 theme 3D 74:75 arg1 map 82:84 3D HPLC map 74:84 3D HPLC map 74:84 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 35452093 4 1 with conjunction 929:939 arg1 data 957:960 multiomics data 946:960 multiomics data 946:960 This liaison will facilitate glycomic analyses of human and other organisms in conjunction with multiomics data. 35452093 3 2 theme new 644:646 arg1 those 668:672 those 668:672 those 668:672 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 3 2 theme new 644:646 arg1 data 653:656 new HPLC data 644:656 new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies 644:775 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 4 3 theme other 910:914 arg1 organisms 916:924 other organisms 910:924 other organisms 910:924 This liaison will facilitate glycomic analyses of human and other organisms in conjunction with multiomics data. 35452093 3 4 dep GlyTouCan 814:822 arg1 Portal 842:847 Portal 842:847 Portal 842:847 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 0 5 theme HPLC 77:80 arg1 map 82:84 3D HPLC map 74:84 3D HPLC map 74:84 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 35452093 2 6 theme oligosaccharides 400:415 arg1 map 384:386 the three-dimensional HPLC map 357:386 the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi 357:474 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 4 7 theme multiomics 946:955 arg1 data 957:960 multiomics data 946:960 multiomics data 946:960 This liaison will facilitate glycomic analyses of human and other organisms in conjunction with multiomics data. 35452093 3 8 theme sulfated 696:703 arg1 glycans 705:711 glucuronylated and sulfated glycans 677:711 glucuronylated and sulfated glycans 677:711 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 3 8 theme sulfated 696:703 arg1 interface 741:749 an improved graphical user interface 714:749 an improved graphical user interface using modern technologies 714:775 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 3 9 theme glycan 792:797 arg1 information 799:809 glycan information 792:809 glycan information in GlyTouCan and the GlyCosmos Portal 792:847 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 1 10 theme useful 156:161 arg1 tool 163:166 a useful tool 154:166 a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides 154:249 High-performance liquid chromatography (HPLC) elution data provide a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides. 35452093 2 11 with oligosaccharides 400:415 arg1 pyridyl-2-amination 422:440 pyridyl-2-amination 422:440 pyridyl-2-amination developed by Dr. Noriko Takahashi 422:474 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 3 12 attach linked 782:787 arg2 version 618:624 version 3 618:626 version 3 618:626 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 3 12 attach linked 782:787 arg1 information 799:809 glycan information 792:809 glycan information in GlyTouCan and the GlyCosmos Portal 792:847 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 2 13 theme Chromatography 314:327 arg1 application 260:270 The web application Glycoanalysis 252:284 The web application Glycoanalysis 252:284 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 2 14 theme three-dimensional 361:377 arg1 map 384:386 the three-dimensional HPLC map 357:386 the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi 357:474 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 0 15 theme GALAXY 0:5 arg1 ver3 7:10 GALAXY ver3 0:10 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 0:85 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 35452093 3 16 theme user 736:739 arg1 glycans 705:711 glucuronylated and sulfated glycans 677:711 glucuronylated and sulfated glycans 677:711 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 3 16 theme user 736:739 arg1 interface 741:749 an improved graphical user interface 714:749 an improved graphical user interface using modern technologies 714:775 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 2 17 dep application 260:270 arg1 Glycoanalysis 272:284 Glycoanalysis 272:284 Glycoanalysis 272:284 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 0 18 theme updated 13:19 arg1 application 25:35 updated web application 13:35 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 0:85 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 35452093 0 19 dep ver3 7:10 arg1 application 25:35 updated web application 13:35 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 0:85 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 35452093 3 20 from information 799:809 arg1 GlyTouCan 814:822 GlyTouCan 814:822 GlyTouCan 814:822 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 3 20 from information 799:809 arg1 GlyCosmos 832:840 GlyCosmos 832:840 GlyCosmos 832:840 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 2 21 theme MS 307:308 arg1 application 260:270 The web application Glycoanalysis 252:284 The web application Glycoanalysis 252:284 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 1 22 theme quantitative 172:183 arg1 profiling 199:207 quantitative glycosylation profiling 172:207 quantitative glycosylation profiling 172:207 High-performance liquid chromatography (HPLC) elution data provide a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides. 35452093 3 23 theme improved 717:724 arg1 glycans 705:711 glucuronylated and sulfated glycans 677:711 glucuronylated and sulfated glycans 677:711 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 3 23 theme improved 717:724 arg1 interface 741:749 an improved graphical user interface 714:749 an improved graphical user interface using modern technologies 714:775 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 1 24 theme High-performance 87:102 arg1 HPLC 127:130 HPLC 127:130 HPLC 127:130 High-performance liquid chromatography (HPLC) elution data provide a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides. 35452093 1 24 theme High-performance 87:102 arg1 chromatography 111:124 High-performance liquid chromatography 87:124 High-performance liquid chromatography (HPLC) elution data 87:144 High-performance liquid chromatography (HPLC) elution data provide a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides. 35452093 1 25 theme glycosylation 185:197 arg1 profiling 199:207 quantitative glycosylation profiling 172:207 quantitative glycosylation profiling 172:207 High-performance liquid chromatography (HPLC) elution data provide a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides. 35452093 3 26 theme graphical 726:734 arg1 glycans 705:711 glucuronylated and sulfated glycans 677:711 glucuronylated and sulfated glycans 677:711 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 3 26 theme graphical 726:734 arg1 interface 741:749 an improved graphical user interface 714:749 an improved graphical user interface using modern technologies 714:775 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 2 27 theme N-linked 391:398 arg1 oligosaccharides 400:415 N-linked oligosaccharides 391:415 N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi 391:474 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 0 28 theme web 21:23 arg1 application 25:35 updated web application 13:35 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 0:85 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 35452093 4 29 theme organisms 916:924 arg1 analyses 888:895 glycomic analyses 879:895 glycomic analyses of human and other organisms 879:924 This liaison will facilitate glycomic analyses of human and other organisms in conjunction with multiomics data. 35452093 0 30 theme glycosylation 41:53 arg1 profiling 55:63 glycosylation profiling 41:63 glycosylation profiling based on 3D HPLC map 41:84 GALAXY ver3: updated web application for glycosylation profiling based on 3D HPLC map. 35452093 1 31 theme liquid 104:109 arg1 HPLC 127:130 HPLC 127:130 HPLC 127:130 High-performance liquid chromatography (HPLC) elution data provide a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides. 35452093 1 31 theme liquid 104:109 arg1 chromatography 111:124 High-performance liquid chromatography 87:124 High-performance liquid chromatography (HPLC) elution data 87:144 High-performance liquid chromatography (HPLC) elution data provide a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides. 35452093 4 32 theme glycomic 879:886 arg1 analyses 888:895 glycomic analyses 879:895 glycomic analyses of human and other organisms 879:924 This liaison will facilitate glycomic analyses of human and other organisms in conjunction with multiomics data. 35452093 2 33 link N-linked 391:398 arg1 oligosaccharides 400:415 N-linked oligosaccharides 391:415 N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi 391:474 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 1 34 theme chromatography 111:124 arg1 data 141:144 High-performance liquid chromatography (HPLC) elution data 87:144 High-performance liquid chromatography (HPLC) elution data 87:144 High-performance liquid chromatography (HPLC) elution data provide a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides. 35452093 3 35 theme modern 757:762 arg1 technologies 764:775 modern technologies 757:775 modern technologies 757:775 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 4 36 theme human 900:904 arg1 analyses 888:895 glycomic analyses 879:895 glycomic analyses of human and other organisms 879:924 This liaison will facilitate glycomic analyses of human and other organisms in conjunction with multiomics data. 35452093 3 37 theme updated 600:606 arg1 GALAXY 608:613 the updated GALAXY 596:613 the updated GALAXY 596:613 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 2 38 theme tissue 561:566 arg1 levels 568:573 tissue levels 561:573 tissue levels 561:573 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 2 39 used used 498:501 arg2 application 260:270 The web application Glycoanalysis 252:284 The web application Glycoanalysis 252:284 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 1 40 theme isomeric 225:232 arg1 oligosaccharides 234:249 isomeric oligosaccharides 225:249 isomeric oligosaccharides 225:249 High-performance liquid chromatography (HPLC) elution data provide a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides. 35452093 3 41 theme HPLC 648:651 arg1 those 668:672 those 668:672 those 668:672 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 3 41 theme HPLC 648:651 arg1 data 653:656 new HPLC data 644:656 new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies 644:775 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 2 42 theme web 256:258 arg1 application 260:270 The web application Glycoanalysis 252:284 The web application Glycoanalysis 252:284 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 2 43 theme HPLC 379:382 arg1 map 384:386 the three-dimensional HPLC map 357:386 the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi 357:474 The web application Glycoanalysis by the Three Axes of MS and Chromatography (GALAXY), which is based on the three-dimensional HPLC map of N-linked oligosaccharides with pyridyl-2-amination developed by Dr. Noriko Takahashi, has been extensively used for N-glycosylation profiling at molecular, cellular, and tissue levels. 35452093 3 44 theme glucuronylated 677:690 arg1 glycans 705:711 glucuronylated and sulfated glycans 677:711 glucuronylated and sulfated glycans 677:711 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 3 44 theme glucuronylated 677:690 arg1 interface 741:749 an improved graphical user interface 714:749 an improved graphical user interface using modern technologies 714:775 Herein, we describe the updated GALAXY as version 3, which includes new HPLC data including those of glucuronylated and sulfated glycans, an improved graphical user interface using modern technologies, and linked to glycan information in GlyTouCan and the GlyCosmos Portal. 35452093 1 45 theme elution 133:139 arg1 data 141:144 High-performance liquid chromatography (HPLC) elution data 87:144 High-performance liquid chromatography (HPLC) elution data 87:144 High-performance liquid chromatography (HPLC) elution data provide a useful tool for quantitative glycosylation profiling, discriminating isomeric oligosaccharides. 36908995 9 0 theme groundwater 1177:1187 arg1 levels 1189:1194 groundwater levels 1177:1194 groundwater levels 1177:1194 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 4 1 theme scanning 524:531 arg1 microscopy 542:551 scanning electron microscopy 524:551 scanning electron microscopy 524:551 ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. 36908995 4 2 theme ZO-CTS 444:449 arg1 system 451:456 the most effective ZO-CTS system 425:456 the most effective ZO-CTS system 425:456 ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. 36908995 9 3 from ZO-CTS 1227:1232 arg1 V 1250:1250 V 1250:1250 V 1250:1250 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 9 3 from ZO-CTS 1227:1232 arg1 F- 1257:1258 F- 1257:1258 F- 1257:1258 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 9 3 from ZO-CTS 1227:1232 arg1 As 1247:1248 As 1247:1248 As 1247:1248 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 6 4 dep capacity 841:848 arg1 V 827:827 V 827:827 V 827:827 It was observed that the combination of ZO with CTS improved the F- and As(V) adsorption capacity most notably at pH 5.5. 36908995 3 5 theme % 343:343 arg1 ZO-CTS 359:364 ZO-CTS 359:364 ZO-CTS 359:364 The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). 36908995 3 5 theme % 343:343 arg1 chitosan 349:356 30% w/w chitosan 341:356 30% w/w chitosan (ZO-CTS) 341:365 The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). 36908995 4 6 theme effective 434:442 arg1 system 451:456 the most effective ZO-CTS system 425:456 the most effective ZO-CTS system 425:456 ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. 36908995 9 7 theme filtration 1144:1153 arg1 studies 1155:1161 Gravity filtration studies 1136:1161 Gravity filtration studies conducted for groundwater levels 1136:1194 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 3 8 theme w/w 345:347 arg1 ZO-CTS 359:364 ZO-CTS 359:364 ZO-CTS 359:364 The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). 36908995 3 8 theme w/w 345:347 arg1 chitosan 349:356 30% w/w chitosan 341:356 30% w/w chitosan (ZO-CTS) 341:365 The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). 36908995 7 9 theme isotherm 928:935 arg1 model 937:941 the Freundlich isotherm model 913:941 the Freundlich isotherm model 913:941 Fluoride adsorption by ZO-CTS followed the Freundlich isotherm model, with an adsorption capacity of 120 mg g-1. 36908995 8 10 theme g-1 1131:1133 arg1 capacity 1111:1118 a capacity 1109:1118 a capacity of 14.8 mg g-1 1109:1133 Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. 36908995 9 11 theme ZO-CTS 1227:1232 arg1 effectiveness 1210:1222 the effectiveness 1206:1222 the effectiveness of ZO-CTS in adsorbing As(V) and F- 1206:1258 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 4 12 theme electron 533:540 arg1 microscopy 542:551 scanning electron microscopy 524:551 scanning electron microscopy 524:551 ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. 36908995 8 13 contain have 1104:1107 arg1 Adsorption 987:996 Adsorption 987:996 Adsorption of As(V) by ZO-CTS 987:1015 Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. 36908995 8 13 contain have 1104:1107 arg2 capacity 1111:1118 a capacity 1109:1118 a capacity of 14.8 mg g-1 1109:1133 Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. 36908995 0 14 from water 116:120 arg1 removal 78:84 the removal 74:84 the removal of fluoride and arsenate from water 74:120 The blending effect of natural polysaccharides with nano-zirconia towards the removal of fluoride and arsenate from water. 36908995 5 15 from nanoparticles 673:685 arg1 size 699:702 size 699:702 size 699:702 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 5 15 from nanoparticles 673:685 arg1 present 721:727 present 721:727 present 721:727 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 1 16 theme microwave-assisted 166:183 arg1 route 207:211 a microwave-assisted one-pot precipitation route 164:211 a microwave-assisted one-pot precipitation route 164:211 Nano-zirconia (ZO) was synthesized using a microwave-assisted one-pot precipitation route. 36908995 0 17 theme arsenate 102:109 arg1 removal 78:84 the removal 74:84 the removal of fluoride and arsenate from water 74:120 The blending effect of natural polysaccharides with nano-zirconia towards the removal of fluoride and arsenate from water. 36908995 4 18 dep transform 491:499 arg1 infrared 501:508 infrared 501:508 transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy 491:607 ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. 36908995 9 19 from effectiveness 1210:1222 arg1 V 1250:1250 V 1250:1250 V 1250:1250 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 9 19 from effectiveness 1210:1222 arg1 F- 1257:1258 F- 1257:1258 F- 1257:1258 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 9 19 from effectiveness 1210:1222 arg1 As 1247:1248 As 1247:1248 As 1247:1248 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 10 20 theme ZO-CTS 1295:1300 arg1 ability 1280:1286 The ability 1276:1286 The ability of the ZO-CTS in removing Cd(II) and Pb(II) 1276:1330 The ability of the ZO-CTS in removing Cd(II) and Pb(II) was also investigated, and no such enhancement was observed, and found the neat ZO was the most potent sorbent here. 36908995 10 21 theme such 1362:1365 arg1 enhancement 1367:1377 no such enhancement 1359:1377 no such enhancement 1359:1377 The ability of the ZO-CTS in removing Cd(II) and Pb(II) was also investigated, and no such enhancement was observed, and found the neat ZO was the most potent sorbent here. 36908995 3 22 theme F- 404:405 arg1 uptake 394:399 enhanced uptake 385:399 enhanced uptake of F- and As(V) 385:415 The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). 36908995 0 23 theme blending 4:11 arg1 effect 13:18 The blending effect 0:18 The blending effect of natural polysaccharides with nano-zirconia towards the removal of fluoride and arsenate from water. 0:121 The blending effect of natural polysaccharides with nano-zirconia towards the removal of fluoride and arsenate from water. 36908995 4 24 dep Fourier 483:489 arg1 transform 491:499 transform 491:499 transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy 491:607 ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. 36908995 7 25 theme mg 979:980 arg1 g-1 982:984 120 mg g-1 975:984 120 mg g-1 975:984 Fluoride adsorption by ZO-CTS followed the Freundlich isotherm model, with an adsorption capacity of 120 mg g-1. 36908995 5 26 attach present 721:727 arg1 nanoparticles 673:685 nanoparticles 673:685 nanoparticles 673:685 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 5 26 attach present 721:727 arg2 ZO 714:715 ZO 714:715 ZO 714:715 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 5 26 attach present 721:727 arg1 form 746:749 the amorphous form 732:749 the amorphous form 732:749 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 2 27 theme w/w 308:310 arg1 ratios 312:317 different w/w ratios 298:317 different w/w ratios 298:317 Two biopolymers, chitosan (CTS) and carboxymethyl cellulose were blended with ZO at different w/w ratios. 36908995 3 28 theme enhanced 385:392 arg1 uptake 394:399 enhanced uptake 385:399 enhanced uptake of F- and As(V) 385:415 The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). 36908995 5 29 from present 721:727 arg1 nanoparticles 673:685 nanoparticles 673:685 nanoparticles 673:685 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 5 29 from present 721:727 arg1 form 746:749 the amorphous form 732:749 the amorphous form 732:749 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 7 30 theme g-1 982:984 arg1 capacity 963:970 an adsorption capacity 949:970 an adsorption capacity of 120 mg g-1 949:984 Fluoride adsorption by ZO-CTS followed the Freundlich isotherm model, with an adsorption capacity of 120 mg g-1. 36908995 2 31 theme different 298:306 arg1 ratios 312:317 different w/w ratios 298:317 different w/w ratios 298:317 Two biopolymers, chitosan (CTS) and carboxymethyl cellulose were blended with ZO at different w/w ratios. 36908995 1 32 theme one-pot 185:191 arg1 route 207:211 a microwave-assisted one-pot precipitation route 164:211 a microwave-assisted one-pot precipitation route 164:211 Nano-zirconia (ZO) was synthesized using a microwave-assisted one-pot precipitation route. 36908995 8 33 theme Freundlich 1060:1069 arg1 isotherm 1071:1078 Freundlich isotherm 1060:1078 Freundlich isotherm 1060:1078 Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. 36908995 4 34 theme photoelectron 582:594 arg1 spectroscopy 596:607 X-ray photoelectron spectroscopy 576:607 X-ray photoelectron spectroscopy 576:607 ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. 36908995 7 35 theme 120 975:977 arg1 mg 979:980 mg 979:980 mg 979:980 Fluoride adsorption by ZO-CTS followed the Freundlich isotherm model, with an adsorption capacity of 120 mg g-1. 36908995 5 36 from size 699:702 arg1 nanoparticles 673:685 nanoparticles 673:685 nanoparticles 673:685 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 4 37 theme X-ray 576:580 arg1 spectroscopy 596:607 X-ray photoelectron spectroscopy 576:607 X-ray photoelectron spectroscopy 576:607 ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. 36908995 0 38 theme polysaccharides 31:45 arg1 effect 13:18 The blending effect 0:18 The blending effect of natural polysaccharides with nano-zirconia towards the removal of fluoride and arsenate from water. 0:121 The blending effect of natural polysaccharides with nano-zirconia towards the removal of fluoride and arsenate from water. 36908995 5 39 contain containing 662:671 arg2 nanoparticles 673:685 nanoparticles 673:685 nanoparticles 673:685 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 5 39 contain containing 662:671 arg1 system 655:660 a composite system 643:660 a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form 643:749 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 7 40 theme adsorption 952:961 arg1 capacity 963:970 an adsorption capacity 949:970 an adsorption capacity of 120 mg g-1 949:984 Fluoride adsorption by ZO-CTS followed the Freundlich isotherm model, with an adsorption capacity of 120 mg g-1. 36908995 8 41 theme mg 1128:1129 arg1 g-1 1131:1133 14.8 mg g-1 1123:1133 14.8 mg g-1 1123:1133 Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. 36908995 6 42 with combination 777:787 arg1 CTS 800:802 CTS 800:802 CTS 800:802 It was observed that the combination of ZO with CTS improved the F- and As(V) adsorption capacity most notably at pH 5.5. 36908995 0 43 theme natural 23:29 arg1 polysaccharides 31:45 natural polysaccharides 23:45 natural polysaccharides with nano-zirconia 23:64 The blending effect of natural polysaccharides with nano-zirconia towards the removal of fluoride and arsenate from water. 36908995 8 44 theme isotherm 1071:1078 arg1 models 1080:1085 both the Langmuir and Freundlich isotherm models 1038:1085 models 1080:1085 Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. 36908995 5 45 from nm 693:694 arg1 size 699:702 size 699:702 size 699:702 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 9 46 from As 1247:1248 arg1 effectiveness 1210:1222 the effectiveness 1206:1222 the effectiveness of ZO-CTS in adsorbing As(V) and F- 1206:1258 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 7 47 theme Freundlich 917:926 arg1 model 937:941 the Freundlich isotherm model 913:941 the Freundlich isotherm model 913:941 Fluoride adsorption by ZO-CTS followed the Freundlich isotherm model, with an adsorption capacity of 120 mg g-1. 36908995 3 48 theme As 411:412 arg1 uptake 394:399 enhanced uptake 385:399 enhanced uptake of F- and As(V) 385:415 The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). 36908995 5 49 theme nm 693:694 arg1 nanoparticles 673:685 nanoparticles 673:685 nanoparticles 673:685 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 8 50 theme As 1001:1002 arg1 Adsorption 987:996 Adsorption 987:996 Adsorption of As(V) by ZO-CTS 987:1015 Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. 36908995 10 51 dep potent 1428:1433 arg1 sorbent 1435:1441 sorbent 1435:1441 sorbent here 1435:1446 The ability of the ZO-CTS in removing Cd(II) and Pb(II) was also investigated, and no such enhancement was observed, and found the neat ZO was the most potent sorbent here. 36908995 5 52 from form 746:749 arg1 present 721:727 present 721:727 present 721:727 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 5 53 theme amorphous 736:744 arg1 form 746:749 the amorphous form 732:749 the amorphous form 732:749 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 3 54 theme 30 341:342 arg1 % 343:343 % 343:343 % 343:343 The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). 36908995 9 55 from F- 1257:1258 arg1 effectiveness 1210:1222 the effectiveness 1206:1222 the effectiveness of ZO-CTS in adsorbing As(V) and F- 1206:1258 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 6 56 theme ZO 792:793 arg1 combination 777:787 the combination 773:787 the combination of ZO with CTS 773:802 It was observed that the combination of ZO with CTS improved the F- and As(V) adsorption capacity most notably at pH 5.5. 36908995 6 57 theme adsorption 830:839 arg1 capacity 841:848 As(V) adsorption capacity 824:848 As(V) adsorption capacity 824:848 It was observed that the combination of ZO with CTS improved the F- and As(V) adsorption capacity most notably at pH 5.5. 36908995 5 58 theme composite 645:653 arg1 system 655:660 a composite system 643:660 a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form 643:749 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 2 59 theme carboxymethyl 250:262 arg1 cellulose 264:272 carboxymethyl cellulose 250:272 carboxymethyl cellulose 250:272 Two biopolymers, chitosan (CTS) and carboxymethyl cellulose were blended with ZO at different w/w ratios. 36908995 5 60 located present 721:727 arg1 nanoparticles 673:685 nanoparticles 673:685 nanoparticles 673:685 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 5 60 located present 721:727 arg2 ZO 714:715 ZO 714:715 ZO 714:715 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 5 60 located present 721:727 arg1 form 746:749 the amorphous form 732:749 the amorphous form 732:749 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 7 61 theme Fluoride 874:881 arg1 adsorption 883:892 Fluoride adsorption 874:892 Fluoride adsorption by ZO-CTS 874:902 Fluoride adsorption by ZO-CTS followed the Freundlich isotherm model, with an adsorption capacity of 120 mg g-1. 36908995 4 62 theme X-ray 554:558 arg1 diffraction 560:570 X-ray diffraction 554:570 X-ray diffraction 554:570 ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. 36908995 5 63 theme system 655:660 arg1 formation 630:638 the formation 626:638 the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form 626:749 These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. 36908995 10 64 dep found 1397:1401 arg1 potent 1428:1433 potent 1428:1433 potent 1428:1433 The ability of the ZO-CTS in removing Cd(II) and Pb(II) was also investigated, and no such enhancement was observed, and found the neat ZO was the most potent sorbent here. 36908995 9 65 theme 5.5 1271:1273 arg1 pH 1265:1266 a pH 1263:1266 a pH of 5.5 1263:1273 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 8 66 theme 14.8 1123:1126 arg1 mg 1128:1129 mg 1128:1129 mg 1128:1129 Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. 36908995 1 67 theme precipitation 193:205 arg1 route 207:211 a microwave-assisted one-pot precipitation route 164:211 a microwave-assisted one-pot precipitation route 164:211 Nano-zirconia (ZO) was synthesized using a microwave-assisted one-pot precipitation route. 36908995 10 68 theme neat 1407:1410 arg1 ZO 1412:1413 the neat ZO 1403:1413 the neat ZO 1403:1413 The ability of the ZO-CTS in removing Cd(II) and Pb(II) was also investigated, and no such enhancement was observed, and found the neat ZO was the most potent sorbent here. 36908995 6 69 theme As 824:825 arg1 capacity 841:848 As(V) adsorption capacity 824:848 As(V) adsorption capacity 824:848 It was observed that the combination of ZO with CTS improved the F- and As(V) adsorption capacity most notably at pH 5.5. 36908995 9 70 theme Gravity 1136:1142 arg1 studies 1155:1161 Gravity filtration studies 1136:1161 Gravity filtration studies conducted for groundwater levels 1136:1194 Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. 36908995 3 71 with formulation 324:334 arg1 ZO-CTS 359:364 ZO-CTS 359:364 ZO-CTS 359:364 The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). 36908995 3 71 with formulation 324:334 arg1 chitosan 349:356 30% w/w chitosan 341:356 30% w/w chitosan (ZO-CTS) 341:365 The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). 36908995 0 72 with polysaccharides 31:45 arg1 nano-zirconia 52:64 nano-zirconia 52:64 nano-zirconia 52:64 The blending effect of natural polysaccharides with nano-zirconia towards the removal of fluoride and arsenate from water. 36908995 8 73 theme Langmuir 1047:1054 arg1 models 1080:1085 both the Langmuir and Freundlich isotherm models 1038:1085 models 1080:1085 Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. 36908995 0 74 theme fluoride 89:96 arg1 removal 78:84 the removal 74:84 the removal of fluoride and arsenate from water 74:120 The blending effect of natural polysaccharides with nano-zirconia towards the removal of fluoride and arsenate from water. 37131708 2 0 theme aeruginosa 358:367 arg1 clearance 342:350 clearance 342:350 clearance 342:350 In particular, phagocytosis by neutrophils and macrophages is a key mechanism that modulates host control and clearance of P. aeruginosa . 37131708 2 0 theme aeruginosa 358:367 arg1 control 330:336 host control 325:336 host control 325:336 In particular, phagocytosis by neutrophils and macrophages is a key mechanism that modulates host control and clearance of P. aeruginosa . 37131708 12 1 theme aeruginosa- 2146:2156 arg1 interactions 2165:2176 P. aeruginosa- glycan interactions 2143:2176 P. aeruginosa- glycan interactions 2143:2176 This study provides an increased understanding of the glycans bound by P. aeruginosa , and furthermore, provides a useful dataset for future studies of P. aeruginosa- glycan interactions. 37131708 4 2 attach present 700:706 arg2 structures 689:698 simple and complex glycan structures 663:698 simple and complex glycan structures present at the host cell surface 663:731 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 4 2 attach present 700:706 arg1 surface 725:731 the host cell surface 711:731 the host cell surface 711:731 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 2 3 theme key 296:298 arg1 mechanism 300:308 a key mechanism 294:308 a key mechanism that modulates host control and clearance of P. aeruginosa 294:367 In particular, phagocytosis by neutrophils and macrophages is a key mechanism that modulates host control and clearance of P. aeruginosa . 37131708 2 3 theme key 296:298 arg1 phagocytosis 247:258 phagocytosis 247:258 phagocytosis by neutrophils and macrophages 247:289 In particular, phagocytosis by neutrophils and macrophages is a key mechanism that modulates host control and clearance of P. aeruginosa . 37131708 4 4 theme complex 674:680 arg1 structures 689:698 simple and complex glycan structures 663:698 simple and complex glycan structures present at the host cell surface 663:731 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 10 5 theme glycans 1569:1575 arg1 variety 1558:1564 a variety 1556:1564 a variety of glycans 1556:1575 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 10 5 theme glycans 1569:1575 arg1 glycans 1569:1575 glycans 1569:1575 glycans 1569:1575 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 11 6 theme host 1956:1959 arg1 cell-binding 1961:1972 host cell-binding 1956:1972 host cell-binding 1956:1972 Here we extend this work by studying the glycans used by P. aeruginosa PAO1 to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe. 37131708 7 7 theme array 1101:1105 arg1 use 1054:1056 the use 1050:1056 the use of exogenous N-linked glycans and a glycan array 1050:1105 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 2 8 theme host 325:328 arg1 control 330:336 host control 325:336 host control 325:336 In particular, phagocytosis by neutrophils and macrophages is a key mechanism that modulates host control and clearance of P. aeruginosa . 37131708 1 9 theme innate 215:220 arg1 immunity 222:229 fully functional innate immunity 198:229 fully functional innate immunity 198:229 Pseudomonas aeruginosa is an opportunistic pathogen that can establish acute and chronic infections in individuals that lack fully functional innate immunity. 37131708 6 10 theme host 972:975 arg1 cells 988:992 host phagocytic cells 972:992 host phagocytic cells 972:992 However, the suite of glycans that P. aeruginosa binds to on host phagocytic cells remains poorly characterized. 37131708 4 11 theme simple 663:668 arg1 structures 689:698 simple and complex glycan structures 663:698 simple and complex glycan structures present at the host cell surface 663:731 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 7 12 theme glycans 1080:1086 arg1 use 1054:1056 the use 1050:1056 the use of exogenous N-linked glycans and a glycan array 1050:1105 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 5 13 theme phagocytes 837:846 arg1 surface 826:832 the cell surface 817:832 the cell surface of phagocytes 817:846 We have previously shown that endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes mediate binding and subsequent phagocytosis of P. aeruginosa . 37131708 9 14 theme P. 1492:1493 arg1 binding 1513:1519 P. aeruginosa glycan binding 1492:1519 P. aeruginosa glycan binding 1492:1519 We discuss of findings in the context of previous reports of P. aeruginosa glycan binding. 37131708 8 15 link N-linked 1389:1396 arg1 glycans 1422:1428 exogenous N-linked mono- and di-saccharide glycans 1379:1428 exogenous N-linked mono- and di-saccharide glycans 1379:1428 Consistent with these findings, we were able to competitively inhibit bacterial adherence and uptake by the addition of exogenous N-linked mono- and di-saccharide glycans. 37131708 3 16 with Individuals 371:381 arg1 neutropenia 388:398 neutropenia 388:398 neutropenia 388:398 Individuals with neutropenia or cystic fibrosis are highly susceptible to P. aeruginosa infection thus underscoring the importance of the host innate immune response. 37131708 3 16 with Individuals 371:381 arg1 fibrosis 410:417 cystic fibrosis 403:417 cystic fibrosis 403:417 Individuals with neutropenia or cystic fibrosis are highly susceptible to P. aeruginosa infection thus underscoring the importance of the host innate immune response. 37131708 7 17 theme exogenous 1061:1069 arg1 glycans 1080:1086 exogenous N-linked glycans 1061:1086 exogenous N-linked glycans 1061:1086 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 9 18 theme glycan 1506:1511 arg1 binding 1513:1519 P. aeruginosa glycan binding 1492:1519 P. aeruginosa glycan binding 1492:1519 We discuss of findings in the context of previous reports of P. aeruginosa glycan binding. 37131708 12 19 theme glycans 2045:2051 arg1 understanding 2024:2036 an increased understanding 2011:2036 an increased understanding of the glycans bound by P. aeruginosa 2011:2074 This study provides an increased understanding of the glycans bound by P. aeruginosa , and furthermore, provides a useful dataset for future studies of P. aeruginosa- glycan interactions. 37131708 12 20 theme interactions 2165:2176 arg1 studies 2132:2138 future studies 2125:2138 future studies of P. aeruginosa- glycan interactions 2125:2176 This study provides an increased understanding of the glycans bound by P. aeruginosa , and furthermore, provides a useful dataset for future studies of P. aeruginosa- glycan interactions. 37131708 1 21 theme acute 144:148 arg1 infections 162:171 acute and chronic infections 144:171 acute and chronic infections 144:171 Pseudomonas aeruginosa is an opportunistic pathogen that can establish acute and chronic infections in individuals that lack fully functional innate immunity. 37131708 2 22 from mechanism 300:308 arg1 particular 235:244 particular 235:244 particular 235:244 In particular, phagocytosis by neutrophils and macrophages is a key mechanism that modulates host control and clearance of P. aeruginosa . 37131708 8 23 theme bacterial 1329:1337 arg1 adherence 1339:1347 bacterial adherence 1329:1347 bacterial adherence 1329:1347 Consistent with these findings, we were able to competitively inhibit bacterial adherence and uptake by the addition of exogenous N-linked mono- and di-saccharide glycans. 37131708 10 24 dep IMPORTANCE 1522:1531 arg1 aeruginosa 1536:1545 P. aeruginosa 1533:1545 IMPORTANCE P. aeruginosa 1522:1545 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 11 25 dep extend 1766:1771 arg1 using 1869:1873 using 1869:1873 using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe 1869:1988 Here we extend this work by studying the glycans used by P. aeruginosa PAO1 to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe. 37131708 11 25 dep extend 1766:1771 arg1 studying 1786:1793 studying 1786:1793 studying the glycans used by P. aeruginosa PAO1 to bind to phagocytic cells 1786:1860 Here we extend this work by studying the glycans used by P. aeruginosa PAO1 to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe. 37131708 11 26 theme molecules 1924:1932 arg1 suite 1910:1914 the suite 1906:1914 the suite of such molecules that could facilitate host cell-binding by this microbe 1906:1988 Here we extend this work by studying the glycans used by P. aeruginosa PAO1 to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe. 37131708 1 27 theme chronic 154:160 arg1 infections 162:171 acute and chronic infections 144:171 acute and chronic infections 144:171 Pseudomonas aeruginosa is an opportunistic pathogen that can establish acute and chronic infections in individuals that lack fully functional innate immunity. 37131708 4 28 theme host 715:718 arg1 surface 725:731 the host cell surface 711:731 the host cell surface 711:731 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 4 29 dep host 567:570 arg1 cells 586:590 innate immune cells 572:590 innate immune cells 572:590 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 4 30 theme Cell-to-cell 538:549 arg1 contact 551:557 Cell-to-cell contact 538:557 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, 538:643 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 12 31 theme glycan 2158:2163 arg1 interactions 2165:2176 P. aeruginosa- glycan interactions 2143:2176 P. aeruginosa- glycan interactions 2143:2176 This study provides an increased understanding of the glycans bound by P. aeruginosa , and furthermore, provides a useful dataset for future studies of P. aeruginosa- glycan interactions. 37131708 11 32 dep P. 1815:1816 arg1 aeruginosa 1818:1827 aeruginosa 1818:1827 aeruginosa 1818:1827 Here we extend this work by studying the glycans used by P. aeruginosa PAO1 to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe. 37131708 7 33 attach attaches 1147:1154 arg1 subset 1161:1166 a subset 1159:1166 a subset 1159:1166 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 7 33 attach attaches 1147:1154 arg2 PAO1 1127:1130 P. aeruginosa PAO1 1113:1130 P. aeruginosa PAO1 1113:1130 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 10 34 theme aeruginosa- 1640:1650 arg1 number 1627:1632 a number 1625:1632 a number of P. aeruginosa- encoded receptors and target ligands 1625:1687 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 3 35 theme cystic 403:408 arg1 fibrosis 410:417 cystic fibrosis 403:417 cystic fibrosis 403:417 Individuals with neutropenia or cystic fibrosis are highly susceptible to P. aeruginosa infection thus underscoring the importance of the host innate immune response. 37131708 5 36 theme endogenous 764:773 arg1 glycans 796:802 endogenous polyanionic N-linked glycans 764:802 endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes 764:846 We have previously shown that endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes mediate binding and subsequent phagocytosis of P. aeruginosa . 37131708 8 37 theme exogenous 1379:1387 arg1 glycans 1422:1428 exogenous N-linked mono- and di-saccharide glycans 1379:1428 exogenous N-linked mono- and di-saccharide glycans 1379:1428 Consistent with these findings, we were able to competitively inhibit bacterial adherence and uptake by the addition of exogenous N-linked mono- and di-saccharide glycans. 37131708 3 38 theme P. 445:446 arg1 infection 459:467 P. aeruginosa infection 445:467 P. aeruginosa infection 445:467 Individuals with neutropenia or cystic fibrosis are highly susceptible to P. aeruginosa infection thus underscoring the importance of the host innate immune response. 37131708 8 39 theme mono- 1398:1402 arg1 glycans 1422:1428 exogenous N-linked mono- and di-saccharide glycans 1379:1428 exogenous N-linked mono- and di-saccharide glycans 1379:1428 Consistent with these findings, we were able to competitively inhibit bacterial adherence and uptake by the addition of exogenous N-linked mono- and di-saccharide glycans. 37131708 12 40 theme future 2125:2130 arg1 studies 2132:2138 future studies 2125:2138 future studies of P. aeruginosa- glycan interactions 2125:2176 This study provides an increased understanding of the glycans bound by P. aeruginosa , and furthermore, provides a useful dataset for future studies of P. aeruginosa- glycan interactions. 37131708 10 41 theme target 1674:1679 arg1 ligands 1681:1687 target ligands 1674:1687 target ligands 1674:1687 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 7 42 theme glycans 1171:1177 arg1 subset 1161:1166 a subset 1159:1166 a subset 1159:1166 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 8 43 theme di-saccharide 1408:1420 arg1 glycans 1422:1428 exogenous N-linked mono- and di-saccharide glycans 1379:1428 exogenous N-linked mono- and di-saccharide glycans 1379:1428 Consistent with these findings, we were able to competitively inhibit bacterial adherence and uptake by the addition of exogenous N-linked mono- and di-saccharide glycans. 37131708 0 44 theme Profile 33:39 arg1 Assessment 0:9 Assessment 0:9 Assessment of the Glycan-Binding Profile of Pseudomonas aeruginosa 0:65 Assessment of the Glycan-Binding Profile of Pseudomonas aeruginosa PAO1. 37131708 10 45 with interaction 1592:1602 arg1 cells 1614:1618 host cells 1609:1618 host cells 1609:1618 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 7 46 theme glycan 1240:1245 arg1 structures 1247:1256 more complex glycan structures 1227:1256 more complex glycan structures 1227:1256 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 3 47 theme innate 514:519 arg1 response 528:535 the host innate immune response 505:535 the host innate immune response 505:535 Individuals with neutropenia or cystic fibrosis are highly susceptible to P. aeruginosa infection thus underscoring the importance of the host innate immune response. 37131708 5 48 theme cell 821:824 arg1 surface 826:832 the cell surface 817:832 the cell surface of phagocytes 817:846 We have previously shown that endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes mediate binding and subsequent phagocytosis of P. aeruginosa . 37131708 4 49 theme innate 572:577 arg1 cells 586:590 innate immune cells 572:590 innate immune cells 572:590 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 5 50 theme polyanionic 775:785 arg1 glycans 796:802 endogenous polyanionic N-linked glycans 764:802 endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes 764:846 We have previously shown that endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes mediate binding and subsequent phagocytosis of P. aeruginosa . 37131708 11 51 theme glycan 1877:1882 arg1 array 1884:1888 a glycan array 1875:1888 a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe 1875:1988 Here we extend this work by studying the glycans used by P. aeruginosa PAO1 to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe. 37131708 10 52 dep aeruginosa- 1640:1650 arg1 receptors 1660:1668 encoded receptors 1652:1668 encoded receptors 1652:1668 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 10 52 dep aeruginosa- 1640:1650 arg1 ligands 1681:1687 target ligands 1674:1687 target ligands 1674:1687 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 7 53 link N-linked 1071:1078 arg1 glycans 1080:1086 exogenous N-linked glycans 1061:1086 exogenous N-linked glycans 1061:1086 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 10 54 theme host 1609:1612 arg1 cells 1614:1618 host cells 1609:1618 host cells 1609:1618 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 8 55 with Consistent 1259:1268 arg1 findings 1281:1288 these findings 1275:1288 these findings 1275:1288 Consistent with these findings, we were able to competitively inhibit bacterial adherence and uptake by the addition of exogenous N-linked mono- and di-saccharide glycans. 37131708 3 56 theme response 528:535 arg1 importance 491:500 the importance 487:500 the importance of the host innate immune response 487:535 Individuals with neutropenia or cystic fibrosis are highly susceptible to P. aeruginosa infection thus underscoring the importance of the host innate immune response. 37131708 6 57 theme glycans 933:939 arg1 suite 924:928 the suite 920:928 the suite of glycans that P. aeruginosa binds to on host phagocytic cells 920:992 However, the suite of glycans that P. aeruginosa binds to on host phagocytic cells remains poorly characterized. 37131708 7 58 theme P. 1113:1114 arg1 PAO1 1127:1130 P. aeruginosa PAO1 1113:1130 P. aeruginosa PAO1 1113:1130 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 10 59 theme such 1744:1747 arg1 glycans 1749:1755 such glycans 1744:1755 such glycans 1744:1755 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 12 60 theme increased 2014:2022 arg1 understanding 2024:2036 an increased understanding 2011:2036 an increased understanding of the glycans bound by P. aeruginosa 2011:2074 This study provides an increased understanding of the glycans bound by P. aeruginosa , and furthermore, provides a useful dataset for future studies of P. aeruginosa- glycan interactions. 37131708 4 61 theme first 612:616 arg1 step 618:621 a first step 610:621 a first step in phagocytic uptake 610:642 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 4 61 theme first 612:616 arg1 pathogen 600:607 the pathogen 596:607 the pathogen 596:607 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 7 62 dep P. 1113:1114 arg1 aeruginosa 1116:1125 aeruginosa 1116:1125 aeruginosa 1116:1125 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 7 63 theme glycan 1094:1099 arg1 array 1101:1105 a glycan array 1092:1105 a glycan array 1092:1105 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 5 64 link N-linked 787:794 arg1 glycans 796:802 endogenous polyanionic N-linked glycans 764:802 endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes 764:846 We have previously shown that endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes mediate binding and subsequent phagocytosis of P. aeruginosa . 37131708 5 65 theme aeruginosa 898:907 arg1 binding 856:862 binding 856:862 binding 856:862 We have previously shown that endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes mediate binding and subsequent phagocytosis of P. aeruginosa . 37131708 5 65 theme aeruginosa 898:907 arg1 phagocytosis 879:890 subsequent phagocytosis 868:890 subsequent phagocytosis 868:890 We have previously shown that endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes mediate binding and subsequent phagocytosis of P. aeruginosa . 37131708 4 66 theme glycan 682:687 arg1 structures 689:698 simple and complex glycan structures 663:698 simple and complex glycan structures present at the host cell surface 663:731 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 10 67 theme interaction 1592:1602 arg1 part 1580:1583 part 1580:1583 part of its interaction with host cells 1580:1618 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 1 68 theme functional 204:213 arg1 immunity 222:229 fully functional innate immunity 198:229 fully functional innate immunity 198:229 Pseudomonas aeruginosa is an opportunistic pathogen that can establish acute and chronic infections in individuals that lack fully functional innate immunity. 37131708 6 69 theme phagocytic 977:986 arg1 cells 988:992 host phagocytic cells 972:992 host phagocytic cells 972:992 However, the suite of glycans that P. aeruginosa binds to on host phagocytic cells remains poorly characterized. 37131708 7 70 theme N-linked 1071:1078 arg1 glycans 1080:1086 exogenous N-linked glycans 1061:1086 exogenous N-linked glycans 1061:1086 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 5 71 theme subsequent 868:877 arg1 phagocytosis 879:890 subsequent phagocytosis 868:890 subsequent phagocytosis 868:890 We have previously shown that endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes mediate binding and subsequent phagocytosis of P. aeruginosa . 37131708 4 72 theme cell 720:723 arg1 surface 725:731 the host cell surface 711:731 the host cell surface 711:731 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 9 73 theme binding 1513:1519 arg1 reports 1481:1487 previous reports 1472:1487 previous reports of P. aeruginosa glycan binding 1472:1519 We discuss of findings in the context of previous reports of P. aeruginosa glycan binding. 37131708 7 74 theme complex 1232:1238 arg1 structures 1247:1256 more complex glycan structures 1227:1256 more complex glycan structures 1227:1256 Here we demonstrate, with the use of exogenous N-linked glycans and a glycan array, that P. aeruginosa PAO1 preferentially attaches to a subset of glycans, including a bias towards monosaccharide versus more complex glycan structures. 37131708 11 75 theme such 1919:1922 arg1 molecules 1924:1932 such molecules 1919:1932 such molecules that could facilitate host cell-binding by this microbe 1919:1988 Here we extend this work by studying the glycans used by P. aeruginosa PAO1 to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe. 37131708 9 76 theme previous 1472:1479 arg1 reports 1481:1487 previous reports 1472:1487 previous reports of P. aeruginosa glycan binding 1472:1519 We discuss of findings in the context of previous reports of P. aeruginosa glycan binding. 37131708 4 77 theme present 700:706 arg1 structures 689:698 simple and complex glycan structures 663:698 simple and complex glycan structures present at the host cell surface 663:731 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 5 78 theme N-linked 787:794 arg1 glycans 796:802 endogenous polyanionic N-linked glycans 764:802 endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes 764:846 We have previously shown that endogenous polyanionic N-linked glycans localized to the cell surface of phagocytes mediate binding and subsequent phagocytosis of P. aeruginosa . 37131708 4 79 from step 618:621 arg1 uptake 637:642 phagocytic uptake 626:642 phagocytic uptake 626:642 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 3 80 theme host 509:512 arg1 response 528:535 the host innate immune response 505:535 the host innate immune response 505:535 Individuals with neutropenia or cystic fibrosis are highly susceptible to P. aeruginosa infection thus underscoring the importance of the host innate immune response. 37131708 9 81 theme reports 1481:1487 arg1 context 1461:1467 the context 1457:1467 the context of previous reports of P. aeruginosa glycan binding 1457:1519 We discuss of findings in the context of previous reports of P. aeruginosa glycan binding. 37131708 10 82 theme P. 1637:1638 arg1 aeruginosa- 1640:1650 P. aeruginosa- encoded receptors and target ligands 1637:1687 P. aeruginosa- encoded receptors and target ligands 1637:1687 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 12 83 theme P. 2143:2144 arg1 interactions 2165:2176 P. aeruginosa- glycan interactions 2143:2176 P. aeruginosa- glycan interactions 2143:2176 This study provides an increased understanding of the glycans bound by P. aeruginosa , and furthermore, provides a useful dataset for future studies of P. aeruginosa- glycan interactions. 37131708 3 84 theme aeruginosa 448:457 arg1 infection 459:467 P. aeruginosa infection 445:467 P. aeruginosa infection 445:467 Individuals with neutropenia or cystic fibrosis are highly susceptible to P. aeruginosa infection thus underscoring the importance of the host innate immune response. 37131708 0 85 theme Glycan-Binding 18:31 arg1 Profile 33:39 the Glycan-Binding Profile 14:39 the Glycan-Binding Profile of Pseudomonas aeruginosa 14:65 Assessment of the Glycan-Binding Profile of Pseudomonas aeruginosa PAO1. 37131708 1 86 theme opportunistic 102:114 arg1 aeruginosa 85:94 Pseudomonas aeruginosa 73:94 Pseudomonas aeruginosa 73:94 Pseudomonas aeruginosa is an opportunistic pathogen that can establish acute and chronic infections in individuals that lack fully functional innate immunity. 37131708 1 86 theme opportunistic 102:114 arg1 pathogen 116:123 an opportunistic pathogen 99:123 an opportunistic pathogen that can establish acute and chronic infections in individuals that lack fully functional innate immunity 99:229 Pseudomonas aeruginosa is an opportunistic pathogen that can establish acute and chronic infections in individuals that lack fully functional innate immunity. 37131708 8 87 theme N-linked 1389:1396 arg1 glycans 1422:1428 exogenous N-linked mono- and di-saccharide glycans 1379:1428 exogenous N-linked mono- and di-saccharide glycans 1379:1428 Consistent with these findings, we were able to competitively inhibit bacterial adherence and uptake by the addition of exogenous N-linked mono- and di-saccharide glycans. 37131708 10 88 theme encoded 1652:1658 arg1 receptors 1660:1668 encoded receptors 1652:1668 encoded receptors 1652:1668 IMPORTANCE P. aeruginosa binds to a variety of glycans as part of its interaction with host cells, and a number of P. aeruginosa- encoded receptors and target ligands have been described that allow this microbe to bind to such glycans. 37131708 0 89 theme aeruginosa 56:65 arg1 Profile 33:39 the Glycan-Binding Profile 14:39 the Glycan-Binding Profile of Pseudomonas aeruginosa 14:65 Assessment of the Glycan-Binding Profile of Pseudomonas aeruginosa PAO1. 37131708 4 90 theme immune 579:584 arg1 cells 586:590 innate immune cells 572:590 innate immune cells 572:590 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 8 91 theme glycans 1422:1428 arg1 addition 1367:1374 the addition 1363:1374 the addition of exogenous N-linked mono- and di-saccharide glycans 1363:1428 Consistent with these findings, we were able to competitively inhibit bacterial adherence and uptake by the addition of exogenous N-linked mono- and di-saccharide glycans. 37131708 3 92 theme immune 521:526 arg1 response 528:535 the host innate immune response 505:535 the host innate immune response 505:535 Individuals with neutropenia or cystic fibrosis are highly susceptible to P. aeruginosa infection thus underscoring the importance of the host innate immune response. 37131708 4 93 theme phagocytic 626:635 arg1 uptake 637:642 phagocytic uptake 626:642 phagocytic uptake 626:642 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 9 94 dep P. 1492:1493 arg1 aeruginosa 1495:1504 aeruginosa 1495:1504 aeruginosa 1495:1504 We discuss of findings in the context of previous reports of P. aeruginosa glycan binding. 37131708 11 95 theme P. 1815:1816 arg1 PAO1 1829:1832 P. aeruginosa PAO1 1815:1832 P. aeruginosa PAO1 1815:1832 Here we extend this work by studying the glycans used by P. aeruginosa PAO1 to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe. 37131708 4 96 from surface 725:731 arg1 present 700:706 present 700:706 present 700:706 Cell-to-cell contact between host innate immune cells and the pathogen, a first step in phagocytic uptake, is facilitated by simple and complex glycan structures present at the host cell surface. 37131708 12 97 theme useful 2106:2111 arg1 dataset 2113:2119 a useful dataset 2104:2119 a useful dataset for future studies of P. aeruginosa- glycan interactions 2104:2176 This study provides an increased understanding of the glycans bound by P. aeruginosa , and furthermore, provides a useful dataset for future studies of P. aeruginosa- glycan interactions. 37131708 11 98 theme phagocytic 1845:1854 arg1 cells 1856:1860 phagocytic cells 1845:1860 phagocytic cells 1845:1860 Here we extend this work by studying the glycans used by P. aeruginosa PAO1 to bind to phagocytic cells and by using a glycan array to characterize the suite of such molecules that could facilitate host cell-binding by this microbe. 36171191 11 0 from role 1778:1781 arg1 PFC 1804:1806 the PFC 1800:1806 the PFC underlying depression-like phenotypes in CRS model 1800:1857 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 10 1 theme CRS-exposed 1681:1691 arg1 mice 1693:1696 CRS-exposed mice 1681:1696 CRS-exposed mice 1681:1696 In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. 36171191 11 2 theme prophylactic 1877:1888 arg1 effects 1890:1896 the sustained prophylactic effects 1863:1896 the sustained prophylactic effects of (R)-ketamine 1863:1912 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 8 3 theme mice 1406:1409 arg1 PFC 1387:1389 the PFC 1383:1389 the PFC of CRS-exposed mice 1383:1409 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 11 4 theme miR-132-5p 1786:1795 arg1 role 1778:1781 a novel role 1770:1781 a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model 1770:1857 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 11 4 theme miR-132-5p 1786:1795 arg1 effects 1890:1896 the sustained prophylactic effects 1863:1896 the sustained prophylactic effects of (R)-ketamine 1863:1912 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 11 5 theme -ketamine 1904:1912 arg1 role 1778:1781 a novel role 1770:1781 a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model 1770:1857 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 11 5 theme -ketamine 1904:1912 arg1 effects 1890:1896 the sustained prophylactic effects 1863:1896 the sustained prophylactic effects of (R)-ketamine 1863:1912 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 7 6 from expression 1102:1111 arg1 PFC 1187:1189 the PFC 1183:1189 the PFC of CRS-exposed mice 1183:1209 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 4 7 theme preference 706:715 arg1 test 717:720 sucrose preference test 698:720 sucrose preference test 698:720 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 3 8 theme -ketamine 456:464 arg1 CRS 495:497 CRS 495:497 CRS 495:497 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 3 8 theme -ketamine 456:464 arg1 model 500:504 (R,S)-ketamine in chronic restraint stress (CRS) model 451:504 (R,S)-ketamine in chronic restraint stress (CRS) model 451:504 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 9 9 theme Bdnf 1472:1475 arg1 expression 1458:1467 the expression 1454:1467 the expression of Bdnf and Tgfb1 in the PFC 1454:1496 Administration of agomiR-132-5p decreased the expression of Bdnf and Tgfb1 in the PFC, resulting in depression-like behaviors. 36171191 6 10 theme neurotrophic 982:993 arg1 factor 995:1000 brain-derived neurotrophic factor 968:1000 brain-derived neurotrophic factor (BDNF) expression 968:1018 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 6 10 theme neurotrophic 982:993 arg1 BDNF 1003:1006 BDNF 1003:1006 BDNF 1003:1006 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 11 11 theme R 1902:1902 arg1 -ketamine 1904:1912 (R)-ketamine 1901:1912 (R)-ketamine 1901:1912 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 2 12 theme molecular 230:238 arg1 mechanisms 240:249 the precise molecular mechanisms 218:249 the precise molecular mechanisms underlying its action 218:271 However, the precise molecular mechanisms underlying its action remain elusive. 36171191 9 13 theme Tgfb1 1481:1485 arg1 expression 1458:1467 the expression 1454:1467 the expression of Bdnf and Tgfb1 in the PFC 1454:1496 Administration of agomiR-132-5p decreased the expression of Bdnf and Tgfb1 in the PFC, resulting in depression-like behaviors. 36171191 1 14 theme persistent 145:154 arg1 effects 169:175 persistent prophylactic effects 145:175 persistent prophylactic effects 145:175 (R,S)-ketamine is known to elicit persistent prophylactic effects in rodent models of depression. 36171191 8 15 theme altered 1263:1269 arg1 expression 1271:1280 altered expression 1263:1280 altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice 1263:1409 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 5 16 theme R 897:897 arg1 -ketamine 899:907 (R)-ketamine 896:907 (R)-ketamine 896:907 RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. 36171191 3 17 theme chronic 469:475 arg1 stress 487:492 chronic restraint stress 469:492 chronic restraint stress 469:492 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 5 18 theme cortex 781:786 arg1 analysis 758:765 RNA-sequencing analysis 743:765 RNA-sequencing analysis of prefrontal cortex (PFC) 743:792 RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. 36171191 5 19 theme -ketamine 899:907 arg1 effects 885:891 sustained prophylactic effects 862:891 sustained prophylactic effects of (R)-ketamine 862:907 RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. 36171191 3 20 theme model 500:504 arg1 enantiomer 437:446 a more potent enantiomer 423:446 a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model 423:504 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 3 20 theme model 500:504 arg1 -ketamine 412:420 (R)-ketamine 409:420 (R)-ketamine 409:420 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 0 21 from actions 78:84 arg1 mice 105:108 mice 105:108 mice 105:108 A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice. 36171191 3 22 from -ketamine 456:464 arg1 stress 487:492 chronic restraint stress 469:492 chronic restraint stress 469:492 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 10 23 theme increased 1599:1607 arg1 expression 1609:1618 the increased expression 1595:1618 the increased expression of miR-132-5p 1595:1632 In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. 36171191 5 24 theme RNA-sequencing 743:756 arg1 analysis 758:765 RNA-sequencing analysis 743:765 RNA-sequencing analysis of prefrontal cortex (PFC) 743:792 RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. 36171191 0 25 from role 6:9 arg1 cortex 43:48 the prefrontal cortex 28:48 the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice 28:108 A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice. 36171191 0 26 theme persistent 54:63 arg1 actions 78:84 persistent prophylactic actions 54:84 persistent prophylactic actions of (R)-ketamine in mice 54:108 A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice. 36171191 9 27 theme agomiR-132-5p 1430:1442 arg1 Administration 1412:1425 Administration 1412:1425 Administration of agomiR-132-5p 1412:1442 Administration of agomiR-132-5p decreased the expression of Bdnf and Tgfb1 in the PFC, resulting in depression-like behaviors. 36171191 8 28 dep proteins 1351:1358 arg1 PSD-95 1361:1366 PSD-95 1361:1366 PSD-95 1361:1366 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 8 28 dep proteins 1351:1358 arg1 GluA1 1373:1377 GluA1 1373:1377 GluA1 1373:1377 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 8 28 dep proteins 1351:1358 arg1 proteins 1351:1358 synaptic proteins 1342:1358 synaptic proteins (PSD-95, and GluA1) 1342:1378 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 8 29 theme growth 1319:1324 arg1 factor 1326:1331 transforming growth factor β1 1306:1334 transforming growth factor β1 1306:1334 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 8 29 theme growth 1319:1324 arg1 TGF-β1 1298:1303 TGF-β1 1298:1303 TGF-β1 (transforming growth factor β1) 1298:1335 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 4 30 dep 10 mg/kg 539:546 arg1 day 551:553 1 day 549:553 1 day before CRS 549:564 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 11 31 theme depression-like 1819:1833 arg1 phenotypes 1835:1844 depression-like phenotypes 1819:1844 depression-like phenotypes 1819:1844 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 6 32 theme binding 921:927 arg1 MeCP2 940:944 MeCP2 940:944 MeCP2 940:944 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 6 32 theme binding 921:927 arg1 protein 929:935 Methyl CpG binding protein 2 910:937 Methyl CpG binding protein 2 (MeCP2) 910:945 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 4 33 theme body 593:596 arg1 loss 605:608 body weight loss 593:608 body weight loss 593:608 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 6 34 theme Methyl 910:915 arg1 MeCP2 940:944 MeCP2 940:944 MeCP2 940:944 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 6 34 theme Methyl 910:915 arg1 protein 929:935 Methyl CpG binding protein 2 910:937 Methyl CpG binding protein 2 (MeCP2) 910:945 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 5 35 theme several 808:814 arg1 miRNAs 816:821 several miRNAs 808:821 several miRNAs such as miR-132-5p 808:840 RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. 36171191 5 35 theme several 808:814 arg1 miR-132-5p 831:840 miR-132-5p 831:840 miR-132-5p 831:840 RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. 36171191 8 36 theme synaptic 1342:1349 arg1 PSD-95 1361:1366 PSD-95 1361:1366 PSD-95 1361:1366 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 8 36 theme synaptic 1342:1349 arg1 GluA1 1373:1377 GluA1 1373:1377 GluA1 1373:1377 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 8 36 theme synaptic 1342:1349 arg1 proteins 1351:1358 synaptic proteins 1342:1358 synaptic proteins (PSD-95, and GluA1) 1342:1378 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 1 37 dep -ketamine 116:124 arg1 S 114:114 S 114:114 S 114:114 (R,S)-ketamine is known to elicit persistent prophylactic effects in rodent models of depression. 36171191 1 37 dep -ketamine 116:124 arg1 R 112:112 R 112:112 R 112:112 (R,S)-ketamine is known to elicit persistent prophylactic effects in rodent models of depression. 36171191 0 38 theme miR-132-5p 14:23 arg1 role 6:9 A key role 0:9 A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice. 0:109 A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice. 36171191 7 39 theme genes 1145:1149 arg1 expression 1102:1111 altered expression 1094:1111 altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice 1094:1209 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 3 40 theme molecular 342:350 arg1 s 359:359 novel molecular target(s) 336:360 novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model 336:504 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 4 41 theme sucrose 676:682 arg1 preference 684:693 sucrose preference 676:693 sucrose preference of sucrose preference test in CRS-exposed mice 676:740 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 8 42 theme R 1226:1226 arg1 -ketamine 1228:1236 (R)-ketamine 1225:1236 (R)-ketamine 1225:1236 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 1 43 theme prophylactic 156:167 arg1 effects 169:175 persistent prophylactic effects 145:175 persistent prophylactic effects 145:175 (R,S)-ketamine is known to elicit persistent prophylactic effects in rodent models of depression. 36171191 7 44 dep genes 1145:1149 arg1 Mecp2 1158:1162 Mecp2 1158:1162 Mecp2 1158:1162 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 7 44 dep genes 1145:1149 arg1 Bdnf 1152:1155 Bdnf 1152:1155 Bdnf 1152:1155 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 7 44 dep genes 1145:1149 arg1 Tgfbr2 1172:1177 Tgfbr2 1172:1177 Tgfbr2 1172:1177 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 7 44 dep genes 1145:1149 arg1 Tgfb1 1165:1169 Tgfb1 1165:1169 Tgfb1 1165:1169 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 7 45 theme miR-132-5p 1116:1125 arg1 expression 1102:1111 altered expression 1094:1111 altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice 1094:1209 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 10 46 theme Bdnf 1662:1665 arg1 expression 1648:1657 expression 1648:1657 expression of Bdnf in the PFC of CRS-exposed mice 1648:1696 In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. 36171191 4 47 theme test 656:659 arg1 time 632:635 immobility time 621:635 immobility time of forced swimming test 621:659 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 5 48 theme sustained 862:870 arg1 effects 885:891 sustained prophylactic effects 862:891 sustained prophylactic effects of (R)-ketamine 862:907 RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. 36171191 10 49 theme mice 1693:1696 arg1 PFC 1674:1676 the PFC 1670:1676 the PFC of CRS-exposed mice 1670:1696 In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. 36171191 10 50 from expression 1648:1657 arg1 PFC 1674:1676 the PFC 1670:1676 the PFC of CRS-exposed mice 1670:1696 In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. 36171191 4 51 theme test 717:720 arg1 preference 684:693 sucrose preference 676:693 sucrose preference of sucrose preference test in CRS-exposed mice 676:740 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 2 52 theme precise 222:228 arg1 mechanisms 240:249 the precise molecular mechanisms 218:249 the precise molecular mechanisms underlying its action 218:271 However, the precise molecular mechanisms underlying its action remain elusive. 36171191 1 53 theme depression 197:206 arg1 models 187:192 rodent models 180:192 rodent models of depression 180:206 (R,S)-ketamine is known to elicit persistent prophylactic effects in rodent models of depression. 36171191 4 54 theme CRS-exposed 725:735 arg1 mice 737:740 CRS-exposed mice 725:740 CRS-exposed mice 725:740 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 8 55 theme CRS-exposed 1394:1404 arg1 mice 1406:1409 CRS-exposed mice 1394:1409 CRS-exposed mice 1394:1409 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 10 56 theme antidepressant-like 1712:1730 arg1 effects 1732:1738 antidepressant-like effects 1712:1738 antidepressant-like effects 1712:1738 In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. 36171191 11 57 theme novel 1772:1776 arg1 role 1778:1781 a novel role 1770:1781 a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model 1770:1857 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 4 58 theme R 526:526 arg1 -ketamine 528:536 (R)-ketamine 525:536 (R)-ketamine (10 mg/kg, 1 day before CRS) 525:565 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 7 59 theme R 1057:1057 arg1 -ketamine 1059:1067 (R)-ketamine 1056:1067 (R)-ketamine 1056:1067 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 9 60 from expression 1458:1467 arg1 PFC 1494:1496 the PFC 1490:1496 the PFC 1490:1496 Administration of agomiR-132-5p decreased the expression of Bdnf and Tgfb1 in the PFC, resulting in depression-like behaviors. 36171191 4 61 theme sucrose 698:704 arg1 test 717:720 sucrose preference test 698:720 sucrose preference test 698:720 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 6 62 theme factor 995:1000 arg1 expression 1009:1018 brain-derived neurotrophic factor (BDNF) expression 968:1018 brain-derived neurotrophic factor (BDNF) expression 968:1018 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 0 63 theme -ketamine 92:100 arg1 actions 78:84 persistent prophylactic actions 54:84 persistent prophylactic actions of (R)-ketamine in mice 54:108 A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice. 36171191 11 64 theme CRS 1849:1851 arg1 model 1853:1857 CRS model 1849:1857 CRS model 1849:1857 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 6 65 theme brain-derived 968:980 arg1 factor 995:1000 brain-derived neurotrophic factor 968:1000 brain-derived neurotrophic factor (BDNF) expression 968:1018 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 6 65 theme brain-derived 968:980 arg1 BDNF 1003:1006 BDNF 1003:1006 BDNF 1003:1006 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 3 66 theme restraint 477:485 arg1 stress 487:492 chronic restraint stress 469:492 chronic restraint stress 469:492 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 7 67 theme CRS-exposed 1194:1204 arg1 mice 1206:1209 CRS-exposed mice 1194:1209 CRS-exposed mice 1194:1209 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 11 68 from effects 1890:1896 arg1 PFC 1804:1806 the PFC 1800:1806 the PFC underlying depression-like phenotypes in CRS model 1800:1857 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 10 69 theme antagomiR-132-5p 1570:1585 arg1 administration 1552:1565 administration 1552:1565 administration of antagomiR-132-5p 1552:1585 In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. 36171191 5 70 theme prefrontal 770:779 arg1 cortex 781:786 prefrontal cortex 770:786 prefrontal cortex (PFC) 770:792 RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. 36171191 5 70 theme prefrontal 770:779 arg1 PFC 789:791 PFC 789:791 PFC 789:791 RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. 36171191 11 71 theme sustained 1867:1875 arg1 effects 1890:1896 the sustained prophylactic effects 1863:1896 the sustained prophylactic effects of (R)-ketamine 1863:1912 In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of (R)-ketamine. 36171191 8 72 theme BDNF 1285:1288 arg1 expression 1271:1280 altered expression 1263:1280 altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice 1263:1409 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 4 73 theme forced 640:645 arg1 test 656:659 forced swimming test 640:659 forced swimming test 640:659 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 10 74 theme miR-132-5p 1623:1632 arg1 expression 1609:1618 the increased expression 1595:1618 the increased expression of miR-132-5p 1595:1632 In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. 36171191 7 75 theme mice 1206:1209 arg1 PFC 1187:1189 the PFC 1183:1189 the PFC of CRS-exposed mice 1183:1209 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 8 76 theme MeCP2 1291:1295 arg1 expression 1271:1280 altered expression 1263:1280 altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice 1263:1409 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 8 77 from expression 1271:1280 arg1 PFC 1387:1389 the PFC 1383:1389 the PFC of CRS-exposed mice 1383:1409 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 9 78 theme depression-like 1512:1526 arg1 behaviors 1528:1536 depression-like behaviors 1512:1536 depression-like behaviors 1512:1536 Administration of agomiR-132-5p decreased the expression of Bdnf and Tgfb1 in the PFC, resulting in depression-like behaviors. 36171191 8 79 theme TGF-β1 1298:1303 arg1 expression 1271:1280 altered expression 1263:1280 altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice 1263:1409 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 0 80 theme prophylactic 65:76 arg1 actions 78:84 persistent prophylactic actions 54:84 persistent prophylactic actions of (R)-ketamine in mice 54:108 A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice. 36171191 8 81 theme transforming 1306:1317 arg1 factor 1326:1331 transforming growth factor β1 1306:1334 transforming growth factor β1 1306:1334 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 8 81 theme transforming 1306:1317 arg1 TGF-β1 1298:1303 TGF-β1 1298:1303 TGF-β1 (transforming growth factor β1) 1298:1335 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 6 82 link brain-derived 968:980 arg1 factor 995:1000 brain-derived neurotrophic factor 968:1000 brain-derived neurotrophic factor (BDNF) expression 968:1018 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 6 82 link brain-derived 968:980 arg1 BDNF 1003:1006 BDNF 1003:1006 BDNF 1003:1006 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 4 83 dep -ketamine 528:536 arg1 10 mg/kg 539:546 10 mg/kg 539:546 10 mg/kg 539:546 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 7 84 theme Quantitative 1021:1032 arg1 RT-PCR 1034:1039 Quantitative RT-PCR 1021:1039 Quantitative RT-PCR 1021:1039 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 3 85 theme RNA-sequencing 295:308 arg1 analysis 310:317 RNA-sequencing analysis 295:317 RNA-sequencing analysis 295:317 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 4 86 theme immobility 621:630 arg1 time 632:635 immobility time 621:635 immobility time of forced swimming test 621:659 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 0 87 theme key 2:4 arg1 role 6:9 A key role 0:9 A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice. 0:109 A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice. 36171191 4 88 from preference 684:693 arg1 mice 737:740 CRS-exposed mice 725:740 CRS-exposed mice 725:740 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 6 89 theme CpG 917:919 arg1 MeCP2 940:944 MeCP2 940:944 MeCP2 940:944 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 6 89 theme CpG 917:919 arg1 protein 929:935 Methyl CpG binding protein 2 910:937 Methyl CpG binding protein 2 (MeCP2) 910:945 Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. 36171191 3 90 theme novel 336:340 arg1 s 359:359 novel molecular target(s) 336:360 novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model 336:504 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 8 91 theme proteins 1351:1358 arg1 expression 1271:1280 altered expression 1263:1280 altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice 1263:1409 Furthermore, (R)-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. 36171191 4 92 theme weight 598:603 arg1 loss 605:608 body weight loss 593:608 body weight loss 593:608 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 5 93 theme prophylactic 872:883 arg1 effects 885:891 sustained prophylactic effects 862:891 sustained prophylactic effects of (R)-ketamine 862:907 RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of (R)-ketamine. 36171191 7 94 theme regulated 1135:1143 arg1 genes 1145:1149 its regulated genes 1131:1149 its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) 1131:1178 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 3 95 theme prophylactic 385:396 arg1 effects 398:404 the prophylactic effects 381:404 the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model 381:504 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 0 96 theme prefrontal 32:41 arg1 cortex 43:48 the prefrontal cortex 28:48 the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice 28:108 A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice. 36171191 3 97 theme target 352:357 arg1 s 359:359 novel molecular target(s) 336:360 novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model 336:504 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 3 98 theme -ketamine 412:420 arg1 effects 398:404 the prophylactic effects 381:404 the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model 381:504 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 4 99 with Pretreatment 507:518 arg1 -ketamine 528:536 (R)-ketamine 525:536 (R)-ketamine (10 mg/kg, 1 day before CRS) 525:565 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 3 100 theme R 410:410 arg1 enantiomer 437:446 a more potent enantiomer 423:446 a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model 423:504 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 3 100 theme R 410:410 arg1 -ketamine 412:420 (R)-ketamine 409:420 (R)-ketamine 409:420 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 3 101 dep model 500:504 arg1 S 454:454 S 454:454 S 454:454 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 3 101 dep model 500:504 arg1 R 452:452 R 452:452 R 452:452 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 7 102 theme altered 1094:1100 arg1 expression 1102:1111 altered expression 1094:1111 altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice 1094:1209 Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes (Bdnf, Mecp2, Tgfb1, Tgfbr2) in the PFC of CRS-exposed mice. 36171191 4 103 theme swimming 647:654 arg1 test 656:659 forced swimming test 640:659 forced swimming test 640:659 Pretreatment with (R)-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. 36171191 3 104 theme potent 430:435 arg1 enantiomer 437:446 a more potent enantiomer 423:446 a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model 423:504 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 3 104 theme potent 430:435 arg1 -ketamine 412:420 (R)-ketamine 409:420 (R)-ketamine 409:420 Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R,S)-ketamine in chronic restraint stress (CRS) model. 36171191 1 105 theme rodent 180:185 arg1 models 187:192 rodent models 180:192 rodent models of depression 180:206 (R,S)-ketamine is known to elicit persistent prophylactic effects in rodent models of depression. 36743995 0 0 theme spike 76:80 arg1 protein 82:88 the spike protein 72:88 the spike protein in SARS-CoV-2 72:102 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 5 1 theme N-Acetylglucosamine 846:864 arg1 molecules 866:874 the N-Acetylglucosamine molecules 842:874 the N-Acetylglucosamine molecules 842:874 After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. 36743995 5 2 from stability 947:955 arg1 vicinity 966:973 their vicinity 960:973 their vicinity 960:973 After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. 36743995 5 3 theme N-Acetylglucosamine 907:925 arg1 presence 895:902 the presence 891:902 the presence of N-Acetylglucosamine 891:925 After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. 36743995 5 4 theme full 1008:1011 arg1 structure 1013:1021 the full structure 1004:1021 the full structure 1004:1021 After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. 36743995 1 5 theme effort 148:153 arg1 lot 141:143 A lot 139:143 A lot of effort 139:153 A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. 36743995 1 5 theme effort 148:153 arg1 effort 148:153 effort 148:153 effort 148:153 A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. 36743995 0 6 from Investigation 0:12 arg1 stability 59:67 the stability 55:67 the stability of the spike protein in SARS-CoV-2 55:102 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 3 7 dep flexibility 458:468 arg1 the 454:456 the 454:456 the 454:456 Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. 36743995 0 8 theme protein 82:88 arg1 stability 59:67 the stability 55:67 the stability of the spike protein in SARS-CoV-2 55:102 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 1 9 from enzyme 307:312 arg1 cells 325:329 human cells 319:329 human cells 319:329 A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. 36743995 4 10 from stability 723:731 arg1 SARS-CoV-2 762:771 SARS-CoV-2 762:771 SARS-CoV-2 762:771 We performed molecular dynamics simulations to study the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. 36743995 9 11 theme strategies 1446:1455 arg1 development 1415:1425 the development 1411:1425 the development of new therapeutic strategies 1411:1455 Detailed understanding of glycans is key for the development of new therapeutic strategies. 36743995 8 12 located found 1307:1311 arg2 glycans 1299:1305 the experimentally observed glycans 1271:1305 the experimentally observed glycans found on the spike 1271:1324 We propose which of the experimentally observed glycans found on the spike may be more functional than the others. 36743995 8 12 located found 1307:1311 arg1 spike 1320:1324 the spike 1316:1324 the spike 1316:1324 We propose which of the experimentally observed glycans found on the spike may be more functional than the others. 36743995 5 13 from 100 ns 782:787 arg1 proteins 816:823 the spike proteins 806:823 the spike proteins without and with the N-Acetylglucosamine molecules 806:874 After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. 36743995 7 14 theme S2 1240:1241 arg1 domain 1243:1248 the S2 domain 1236:1248 the S2 domain 1236:1248 We also found that the S1 domain is more flexible than the S2 domain. 36743995 3 15 theme glycans 500:506 arg1 flexibility 458:468 flexibility 458:468 flexibility 458:468 Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. 36743995 3 15 theme glycans 500:506 arg1 diversity 474:482 diversity 474:482 diversity 474:482 Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. 36743995 9 16 theme Detailed 1366:1373 arg1 understanding 1375:1387 Detailed understanding 1366:1387 Detailed understanding of glycans 1366:1398 Detailed understanding of glycans is key for the development of new therapeutic strategies. 36743995 5 17 theme spike 810:814 arg1 proteins 816:823 the spike proteins 806:823 the spike proteins without and with the N-Acetylglucosamine molecules 806:874 After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. 36743995 5 18 theme local 941:945 arg1 stability 947:955 the local stability 937:955 the local stability in their vicinity 937:973 After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. 36743995 6 19 with interaction 1128:1138 arg1 receptor 1171:1178 the ACE2 receptor 1162:1178 the ACE2 receptor 1162:1178 Thus; it can be inferred that the N-Acetylglucosamine moieties can potentially affect the interaction of the S protein with the ACE2 receptor. 36743995 9 20 theme glycans 1392:1398 arg1 understanding 1375:1387 Detailed understanding 1366:1387 Detailed understanding of glycans 1366:1398 Detailed understanding of glycans is key for the development of new therapeutic strategies. 36743995 1 21 theme Spike 259:263 arg1 protein 265:271 the Spike protein 255:271 the Spike protein that binds angiotensin-converting enzyme 2 on human cells 255:329 A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. 36743995 0 22 from protein 82:88 arg1 SARS-CoV-2 93:102 SARS-CoV-2 93:102 SARS-CoV-2 93:102 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 8 23 theme observed 1290:1297 arg1 glycans 1299:1305 the experimentally observed glycans 1271:1305 the experimentally observed glycans found on the spike 1271:1324 We propose which of the experimentally observed glycans found on the spike may be more functional than the others. 36743995 0 24 theme effects 21:27 arg1 Investigation 0:12 Investigation 0:12 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 0:137 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 0 25 theme dynamics 117:124 arg1 simulations 126:136 molecular dynamics simulations 107:136 molecular dynamics simulations 107:136 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 6 26 theme ACE2 1166:1169 arg1 receptor 1171:1178 the ACE2 receptor 1162:1178 the ACE2 receptor 1162:1178 Thus; it can be inferred that the N-Acetylglucosamine moieties can potentially affect the interaction of the S protein with the ACE2 receptor. 36743995 2 27 dep Nowadays 332:339 arg1 researches 347:356 some researches 342:356 some researches 342:356 Nowadays, some researches study the role of the N-linked glycans as potential targets for vaccines and new agents. 36743995 5 28 from effect 994:999 arg1 structure 1013:1021 the full structure 1004:1021 the full structure 1004:1021 After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. 36743995 2 29 theme potential 400:408 arg1 targets 410:416 potential targets 400:416 potential targets for vaccines and new agents 400:444 Nowadays, some researches study the role of the N-linked glycans as potential targets for vaccines and new agents. 36743995 0 30 theme molecular 107:115 arg1 simulations 126:136 molecular dynamics simulations 107:136 molecular dynamics simulations 107:136 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 4 31 theme dynamics 647:654 arg1 simulations 656:666 molecular dynamics simulations 637:666 molecular dynamics simulations 637:666 We performed molecular dynamics simulations to study the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. 36743995 5 32 theme simulation 792:801 arg1 100 ns 782:787 a 100 ns 780:787 a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules 780:874 After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. 36743995 0 33 theme N-Acetylglucosamine 32:50 arg1 effects 21:27 the effects 17:27 the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 17:102 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 3 34 theme glycans 615:621 arg1 precursor 580:588 the precursor 576:588 the precursor of nearly all eukaryotic glycans 576:621 Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. 36743995 3 34 theme glycans 615:621 arg1 moiety 559:564 the N-Acetylglucosamine moiety 535:564 the N-Acetylglucosamine moiety 535:564 Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. 36743995 3 35 theme N-Acetylglucosamine 539:557 arg1 precursor 580:588 the precursor 576:588 the precursor of nearly all eukaryotic glycans 576:621 Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. 36743995 3 35 theme N-Acetylglucosamine 539:557 arg1 moiety 559:564 the N-Acetylglucosamine moiety 535:564 the N-Acetylglucosamine moiety 535:564 Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. 36743995 2 36 theme glycans 389:395 arg1 role 368:371 the role 364:371 the role of the N-linked glycans as potential targets for vaccines and new agents 364:444 Nowadays, some researches study the role of the N-linked glycans as potential targets for vaccines and new agents. 36743995 4 37 gly glycoprotein 746:757 arg1 glycoprotein 746:757 the spike glycoprotein 736:757 the spike glycoprotein 736:757 We performed molecular dynamics simulations to study the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. 36743995 1 38 theme angiotensin-converting 284:305 arg1 enzyme 307:312 angiotensin-converting enzyme 2 284:314 angiotensin-converting enzyme 2 on human cells 284:329 A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. 36743995 3 39 link N-linked 491:498 arg1 glycans 500:506 the N-linked glycans 487:506 the N-linked glycans 487:506 Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. 36743995 1 40 theme therapeutic 195:205 arg1 agents 207:212 therapeutic agents 195:212 therapeutic agents 195:212 A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. 36743995 0 41 from stability 59:67 arg1 Investigation 0:12 Investigation 0:12 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 0:137 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 0 41 from stability 59:67 arg1 SARS-CoV-2 93:102 SARS-CoV-2 93:102 SARS-CoV-2 93:102 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 6 42 theme N-Acetylglucosamine 1072:1090 arg1 moieties 1092:1099 the N-Acetylglucosamine moieties 1068:1099 the N-Acetylglucosamine moieties 1068:1099 Thus; it can be inferred that the N-Acetylglucosamine moieties can potentially affect the interaction of the S protein with the ACE2 receptor. 36743995 2 43 theme new 435:437 arg1 agents 439:444 new agents 435:444 new agents 435:444 Nowadays, some researches study the role of the N-linked glycans as potential targets for vaccines and new agents. 36743995 0 44 from effects 21:27 arg1 stability 59:67 the stability 55:67 the stability of the spike protein in SARS-CoV-2 55:102 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 2 45 link N-linked 380:387 arg1 glycans 389:395 the N-linked glycans 376:395 the N-linked glycans 376:395 Nowadays, some researches study the role of the N-linked glycans as potential targets for vaccines and new agents. 36743995 4 46 from effects 681:687 arg1 stability 723:731 the stability 719:731 the stability of the spike glycoprotein in SARS-CoV-2 719:771 We performed molecular dynamics simulations to study the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. 36743995 0 47 from SARS-CoV-2 93:102 arg1 stability 59:67 the stability 55:67 the stability of the spike protein in SARS-CoV-2 55:102 Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations. 36743995 4 48 theme glycoprotein 746:757 arg1 stability 723:731 the stability 719:731 the stability of the spike glycoprotein in SARS-CoV-2 719:771 We performed molecular dynamics simulations to study the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. 36743995 7 49 theme S1 1204:1205 arg1 domain 1207:1212 the S1 domain 1200:1212 the S1 domain 1200:1212 We also found that the S1 domain is more flexible than the S2 domain. 36743995 7 49 theme S1 1204:1205 arg1 flexible 1222:1229 flexible 1222:1229 flexible 1222:1229 We also found that the S1 domain is more flexible than the S2 domain. 36743995 3 50 theme eukaryotic 604:613 arg1 glycans 615:621 nearly all eukaryotic glycans 593:621 nearly all eukaryotic glycans 593:621 Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. 36743995 4 51 theme spike 740:744 arg1 glycoprotein 746:757 the spike glycoprotein 736:757 the spike glycoprotein 736:757 We performed molecular dynamics simulations to study the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. 36743995 4 52 theme N-Acetylglucosamine 696:714 arg1 effects 681:687 the effects 677:687 the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2 677:771 We performed molecular dynamics simulations to study the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. 36743995 9 53 theme therapeutic 1434:1444 arg1 strategies 1446:1455 new therapeutic strategies 1430:1455 new therapeutic strategies 1430:1455 Detailed understanding of glycans is key for the development of new therapeutic strategies. 36743995 2 54 theme N-linked 380:387 arg1 glycans 389:395 the N-linked glycans 376:395 the N-linked glycans 376:395 Nowadays, some researches study the role of the N-linked glycans as potential targets for vaccines and new agents. 36743995 6 55 theme protein 1149:1155 arg1 interaction 1128:1138 the interaction 1124:1138 the interaction of the S protein with the ACE2 receptor 1124:1178 Thus; it can be inferred that the N-Acetylglucosamine moieties can potentially affect the interaction of the S protein with the ACE2 receptor. 36743995 9 56 theme new 1430:1432 arg1 strategies 1446:1455 new therapeutic strategies 1430:1455 new therapeutic strategies 1430:1455 Detailed understanding of glycans is key for the development of new therapeutic strategies. 36743995 4 57 theme molecular 637:645 arg1 simulations 656:666 molecular dynamics simulations 637:666 molecular dynamics simulations 637:666 We performed molecular dynamics simulations to study the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. 36743995 1 58 theme human 319:323 arg1 cells 325:329 human cells 319:329 human cells 319:329 A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. 36743995 6 59 theme S 1147:1147 arg1 protein 1149:1155 the S protein 1143:1155 the S protein 1143:1155 Thus; it can be inferred that the N-Acetylglucosamine moieties can potentially affect the interaction of the S protein with the ACE2 receptor. 36743995 3 60 theme N-linked 491:498 arg1 glycans 500:506 the N-linked glycans 487:506 the N-linked glycans 487:506 Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. 35168167 0 0 theme genes 88:92 arg1 transcription 58:70 the transcription 54:70 the transcription of cellulosomal genes 54:92 The expression of alternative sigma-I7 factor induces the transcription of cellulosomal genes in the cellulolytic bacterium Clostridium thermocellum. 35168167 1 1 theme cellulosomal 169:180 arg1 CAZymes 211:217 CAZymes 211:217 CAZymes 211:217 The composition of cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum varies depending on the cellulosic substrate used during cultivation. 35168167 1 1 theme cellulosomal 169:180 arg1 enzymes 202:208 cellulosomal carbohydrate-active enzymes 169:208 cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum 169:282 The composition of cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum varies depending on the cellulosic substrate used during cultivation. 35168167 0 2 theme cellulosomal 75:86 arg1 genes 88:92 cellulosomal genes 75:92 cellulosomal genes 75:92 The expression of alternative sigma-I7 factor induces the transcription of cellulosomal genes in the cellulolytic bacterium Clostridium thermocellum. 35168167 2 3 from polysaccharides 382:396 arg1 material 412:419 cellulosic material 401:419 cellulosic material 401:419 C. thermocellum detects the polysaccharides in cellulosic material via anti-sigma factors and expresses the appropriate CAZyme gene via alternative sigma factors, SigIs. 35168167 1 4 theme carbohydrate-active 182:200 arg1 CAZymes 211:217 CAZymes 211:217 CAZymes 211:217 The composition of cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum varies depending on the cellulosic substrate used during cultivation. 35168167 1 4 theme carbohydrate-active 182:200 arg1 enzymes 202:208 cellulosomal carbohydrate-active enzymes 169:208 cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum 169:282 The composition of cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum varies depending on the cellulosic substrate used during cultivation. 35168167 3 5 theme Previous 524:531 arg1 studies 533:539 Previous studies 524:539 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum 524:612 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum have been conducted in vitro or in a heterologous host, because of the limited genetic tools available for C. thermocellum. 35168167 6 6 from ability 1065:1071 arg1 strain 1118:1123 the sigI7 expression strain 1097:1123 the sigI7 expression strain 1097:1123 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 7 7 theme cellulosic 1376:1385 arg1 degradation 1395:1405 cellulosic biomass degradation 1376:1405 cellulosic biomass degradation by C. thermocellum 1376:1424 In this study, we demonstrate the in vivo function of SigI7 and discuss the CAZymes that are important for cellulosic biomass degradation by C. thermocellum. 35168167 0 8 dep bacterium 114:122 arg1 thermocellum 136:147 Clostridium thermocellum 124:147 the cellulolytic bacterium Clostridium thermocellum 97:147 The expression of alternative sigma-I7 factor induces the transcription of cellulosomal genes in the cellulolytic bacterium Clostridium thermocellum. 35168167 4 9 dep in 758:759 arg1 vivo 761:764 vivo 761:764 vivo 761:764 To characterize the in vivo function of SigIs, in the present study, we established a sigI7 gene expression strain of C. thermocellum. 35168167 4 10 theme present 792:798 arg1 study 800:804 the present study 788:804 the present study 788:804 To characterize the in vivo function of SigIs, in the present study, we established a sigI7 gene expression strain of C. thermocellum. 35168167 6 11 from strain 1118:1123 arg1 exoproteome 1080:1090 the exoproteome 1076:1090 the exoproteome from the sigI7 expression strain 1076:1123 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 6 11 from strain 1118:1123 arg1 ability 1065:1071 the degradation ability 1049:1071 the degradation ability of the exoproteome from the sigI7 expression strain 1049:1123 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 3 12 theme gene 569:572 arg1 expression 574:583 CAZyme gene expression 562:583 CAZyme gene expression 562:583 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum have been conducted in vitro or in a heterologous host, because of the limited genetic tools available for C. thermocellum. 35168167 1 13 theme cellulosic 308:317 arg1 substrate 319:327 the cellulosic substrate 304:327 the cellulosic substrate used during cultivation 304:351 The composition of cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum varies depending on the cellulosic substrate used during cultivation. 35168167 3 14 from SigIs 589:593 arg1 thermocellum 601:612 C. thermocellum 598:612 C. thermocellum 598:612 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum have been conducted in vitro or in a heterologous host, because of the limited genetic tools available for C. thermocellum. 35168167 6 15 dep C. 1207:1208 arg1 thermocellum 1210:1221 thermocellum 1210:1221 thermocellum 1210:1221 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 6 16 theme sigI7 1101:1105 arg1 strain 1118:1123 the sigI7 expression strain 1097:1123 the sigI7 expression strain 1097:1123 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 1 17 theme enzymes 202:208 arg1 composition 154:164 The composition 150:164 The composition of cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum 150:282 The composition of cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum varies depending on the cellulosic substrate used during cultivation. 35168167 0 18 theme cellulolytic 101:112 arg1 bacterium 114:122 the cellulolytic bacterium Clostridium thermocellum 97:147 the cellulolytic bacterium Clostridium thermocellum 97:147 The expression of alternative sigma-I7 factor induces the transcription of cellulosomal genes in the cellulolytic bacterium Clostridium thermocellum. 35168167 4 19 theme thermocellum 859:870 arg1 strain 846:851 a sigI7 gene expression strain 822:851 a sigI7 gene expression strain of C. thermocellum 822:870 To characterize the in vivo function of SigIs, in the present study, we established a sigI7 gene expression strain of C. thermocellum. 35168167 7 20 theme SigI7 1323:1327 arg1 function 1311:1318 the in vivo function 1299:1318 the in vivo function of SigI7 1299:1327 In this study, we demonstrate the in vivo function of SigI7 and discuss the CAZymes that are important for cellulosic biomass degradation by C. thermocellum. 35168167 6 21 theme degradation 1053:1063 arg1 ability 1065:1071 the degradation ability 1049:1071 the degradation ability of the exoproteome from the sigI7 expression strain 1049:1123 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 6 22 theme expression 1107:1116 arg1 strain 1118:1123 the sigI7 expression strain 1097:1123 the sigI7 expression strain 1097:1123 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 6 23 from decrease 1037:1044 arg1 ability 1065:1071 the degradation ability 1049:1071 the degradation ability of the exoproteome from the sigI7 expression strain 1049:1123 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 5 24 theme genes 977:981 arg1 expression 943:952 the expression 939:952 the expression of cellulosomal CAZyme genes and cellulosomal scaffold genes 939:1013 Transcriptome analysis of this strain revealed that SigI7 induced the expression of cellulosomal CAZyme genes and cellulosomal scaffold genes. 35168167 5 25 theme strain 904:909 arg1 analysis 887:894 Transcriptome analysis 873:894 Transcriptome analysis of this strain 873:909 Transcriptome analysis of this strain revealed that SigI7 induced the expression of cellulosomal CAZyme genes and cellulosomal scaffold genes. 35168167 7 26 theme in 1303:1304 arg1 function 1311:1318 the in vivo function 1299:1318 the in vivo function of SigI7 1299:1327 In this study, we demonstrate the in vivo function of SigI7 and discuss the CAZymes that are important for cellulosic biomass degradation by C. thermocellum. 35168167 4 27 theme SigIs 778:782 arg1 function 766:773 the in vivo function 754:773 the in vivo function of SigIs 754:782 To characterize the in vivo function of SigIs, in the present study, we established a sigI7 gene expression strain of C. thermocellum. 35168167 0 28 theme alternative 18:28 arg1 factor 39:44 alternative sigma-I7 factor 18:44 alternative sigma-I7 factor 18:44 The expression of alternative sigma-I7 factor induces the transcription of cellulosomal genes in the cellulolytic bacterium Clostridium thermocellum. 35168167 6 29 theme exoproteome 1223:1233 arg1 activity 1191:1198 the activity 1187:1198 the activity of the C. thermocellum exoproteome 1187:1233 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 7 30 theme biomass 1387:1393 arg1 degradation 1395:1405 cellulosic biomass degradation 1376:1405 cellulosic biomass degradation by C. thermocellum 1376:1424 In this study, we demonstrate the in vivo function of SigI7 and discuss the CAZymes that are important for cellulosic biomass degradation by C. thermocellum. 35168167 5 31 theme cellulosomal 987:998 arg1 genes 1009:1013 cellulosomal scaffold genes 987:1013 cellulosomal scaffold genes 987:1013 Transcriptome analysis of this strain revealed that SigI7 induced the expression of cellulosomal CAZyme genes and cellulosomal scaffold genes. 35168167 2 32 theme alternative 490:500 arg1 factors 508:514 alternative sigma factors 490:514 alternative sigma factors 490:514 C. thermocellum detects the polysaccharides in cellulosic material via anti-sigma factors and expresses the appropriate CAZyme gene via alternative sigma factors, SigIs. 35168167 2 33 theme sigma 502:506 arg1 factors 508:514 alternative sigma factors 490:514 alternative sigma factors 490:514 C. thermocellum detects the polysaccharides in cellulosic material via anti-sigma factors and expresses the appropriate CAZyme gene via alternative sigma factors, SigIs. 35168167 6 34 theme C. 1207:1208 arg1 exoproteome 1223:1233 the C. thermocellum exoproteome 1203:1233 the C. thermocellum exoproteome 1203:1233 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 3 35 theme genetic 693:699 arg1 tools 701:705 the limited genetic tools 681:705 the limited genetic tools available for C. thermocellum 681:735 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum have been conducted in vitro or in a heterologous host, because of the limited genetic tools available for C. thermocellum. 35168167 3 36 theme expression 574:583 arg1 regulation 548:557 the regulation 544:557 the regulation of CAZyme gene expression via SigIs in C. thermocellum 544:612 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum have been conducted in vitro or in a heterologous host, because of the limited genetic tools available for C. thermocellum. 35168167 6 37 theme exoproteome 1080:1090 arg1 ability 1065:1071 the degradation ability 1049:1071 the degradation ability of the exoproteome from the sigI7 expression strain 1049:1123 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 0 38 theme factor 39:44 arg1 expression 4:13 The expression 0:13 The expression of alternative sigma-I7 factor 0:44 The expression of alternative sigma-I7 factor induces the transcription of cellulosomal genes in the cellulolytic bacterium Clostridium thermocellum. 35168167 4 39 theme in 758:759 arg1 function 766:773 the in vivo function 754:773 the in vivo function of SigIs 754:782 To characterize the in vivo function of SigIs, in the present study, we established a sigI7 gene expression strain of C. thermocellum. 35168167 6 40 theme gene 1159:1162 arg1 product 1130:1136 the product 1126:1136 the product of the downregulated gene 1126:1162 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 6 40 theme gene 1159:1162 arg1 Clo1313_1002 1165:1176 Clo1313_1002 1165:1176 Clo1313_1002 1165:1176 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 5 41 theme Transcriptome 873:885 arg1 analysis 887:894 Transcriptome analysis 873:894 Transcriptome analysis of this strain 873:909 Transcriptome analysis of this strain revealed that SigI7 induced the expression of cellulosomal CAZyme genes and cellulosomal scaffold genes. 35168167 0 42 theme sigma-I7 30:37 arg1 factor 39:44 alternative sigma-I7 factor 18:44 alternative sigma-I7 factor 18:44 The expression of alternative sigma-I7 factor induces the transcription of cellulosomal genes in the cellulolytic bacterium Clostridium thermocellum. 35168167 3 43 theme heterologous 651:662 arg1 host 664:667 a heterologous host 649:667 a heterologous host 649:667 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum have been conducted in vitro or in a heterologous host, because of the limited genetic tools available for C. thermocellum. 35168167 1 44 theme cellulolytic 236:247 arg1 bacterium 249:257 a cellulolytic bacterium 234:257 a cellulolytic bacterium Clostridium thermocellum 234:282 The composition of cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum varies depending on the cellulosic substrate used during cultivation. 35168167 1 45 dep Clostridium 259:269 arg1 thermocellum 271:282 thermocellum 271:282 thermocellum 271:282 The composition of cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum varies depending on the cellulosic substrate used during cultivation. 35168167 6 46 theme expression 1250:1259 arg1 strain 1261:1266 the sigI7 expression strain 1240:1266 the sigI7 expression strain 1240:1266 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 6 47 theme downregulated 1145:1157 arg1 gene 1159:1162 the downregulated gene 1141:1162 the downregulated gene 1141:1162 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 2 48 theme cellulosic 401:410 arg1 material 412:419 cellulosic material 401:419 cellulosic material 401:419 C. thermocellum detects the polysaccharides in cellulosic material via anti-sigma factors and expresses the appropriate CAZyme gene via alternative sigma factors, SigIs. 35168167 2 49 theme appropriate 462:472 arg1 gene 481:484 the appropriate CAZyme gene 458:484 the appropriate CAZyme gene 458:484 C. thermocellum detects the polysaccharides in cellulosic material via anti-sigma factors and expresses the appropriate CAZyme gene via alternative sigma factors, SigIs. 35168167 3 50 theme limited 685:691 arg1 tools 701:705 the limited genetic tools 681:705 the limited genetic tools available for C. thermocellum 681:735 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum have been conducted in vitro or in a heterologous host, because of the limited genetic tools available for C. thermocellum. 35168167 6 51 theme sigI7 1244:1248 arg1 strain 1261:1266 the sigI7 expression strain 1240:1266 the sigI7 expression strain 1240:1266 However, there was a decrease in the degradation ability of the exoproteome from the sigI7 expression strain; the product of the downregulated gene, Clo1313_1002, rescued the activity of the C. thermocellum exoproteome from the sigI7 expression strain. 35168167 3 52 from studies 533:539 arg1 regulation 548:557 the regulation 544:557 the regulation of CAZyme gene expression via SigIs in C. thermocellum 544:612 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum have been conducted in vitro or in a heterologous host, because of the limited genetic tools available for C. thermocellum. 35168167 3 53 theme CAZyme 562:567 arg1 expression 574:583 CAZyme gene expression 562:583 CAZyme gene expression 562:583 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum have been conducted in vitro or in a heterologous host, because of the limited genetic tools available for C. thermocellum. 35168167 4 54 theme expression 835:844 arg1 strain 846:851 a sigI7 gene expression strain 822:851 a sigI7 gene expression strain of C. thermocellum 822:870 To characterize the in vivo function of SigIs, in the present study, we established a sigI7 gene expression strain of C. thermocellum. 35168167 5 55 theme cellulosomal 957:968 arg1 genes 977:981 cellulosomal CAZyme genes 957:981 cellulosomal CAZyme genes 957:981 Transcriptome analysis of this strain revealed that SigI7 induced the expression of cellulosomal CAZyme genes and cellulosomal scaffold genes. 35168167 7 56 dep in 1303:1304 arg1 vivo 1306:1309 vivo 1306:1309 vivo 1306:1309 In this study, we demonstrate the in vivo function of SigI7 and discuss the CAZymes that are important for cellulosic biomass degradation by C. thermocellum. 35168167 3 57 theme available 707:715 arg1 tools 701:705 the limited genetic tools 681:705 the limited genetic tools available for C. thermocellum 681:735 Previous studies on the regulation of CAZyme gene expression via SigIs in C. thermocellum have been conducted in vitro or in a heterologous host, because of the limited genetic tools available for C. thermocellum. 35168167 5 58 theme genes 1009:1013 arg1 expression 943:952 the expression 939:952 the expression of cellulosomal CAZyme genes and cellulosomal scaffold genes 939:1013 Transcriptome analysis of this strain revealed that SigI7 induced the expression of cellulosomal CAZyme genes and cellulosomal scaffold genes. 35168167 5 59 theme CAZyme 970:975 arg1 genes 977:981 cellulosomal CAZyme genes 957:981 cellulosomal CAZyme genes 957:981 Transcriptome analysis of this strain revealed that SigI7 induced the expression of cellulosomal CAZyme genes and cellulosomal scaffold genes. 35168167 1 60 theme Clostridium 259:269 arg1 bacterium 249:257 a cellulolytic bacterium 234:257 a cellulolytic bacterium Clostridium thermocellum 234:282 The composition of cellulosomal carbohydrate-active enzymes (CAZymes) secreted from a cellulolytic bacterium Clostridium thermocellum varies depending on the cellulosic substrate used during cultivation. 35168167 2 61 theme CAZyme 474:479 arg1 gene 481:484 the appropriate CAZyme gene 458:484 the appropriate CAZyme gene 458:484 C. thermocellum detects the polysaccharides in cellulosic material via anti-sigma factors and expresses the appropriate CAZyme gene via alternative sigma factors, SigIs. 35168167 4 62 theme gene 830:833 arg1 strain 846:851 a sigI7 gene expression strain 822:851 a sigI7 gene expression strain of C. thermocellum 822:870 To characterize the in vivo function of SigIs, in the present study, we established a sigI7 gene expression strain of C. thermocellum. 35168167 5 63 theme scaffold 1000:1007 arg1 genes 1009:1013 cellulosomal scaffold genes 987:1013 cellulosomal scaffold genes 987:1013 Transcriptome analysis of this strain revealed that SigI7 induced the expression of cellulosomal CAZyme genes and cellulosomal scaffold genes. 35168167 4 64 theme sigI7 824:828 arg1 strain 846:851 a sigI7 gene expression strain 822:851 a sigI7 gene expression strain of C. thermocellum 822:870 To characterize the in vivo function of SigIs, in the present study, we established a sigI7 gene expression strain of C. thermocellum. 35168167 2 65 theme anti-sigma 425:434 arg1 factors 436:442 anti-sigma factors 425:442 anti-sigma factors 425:442 C. thermocellum detects the polysaccharides in cellulosic material via anti-sigma factors and expresses the appropriate CAZyme gene via alternative sigma factors, SigIs. 37402017 5 0 theme conjugate 750:758 arg1 characterization 760:775 conjugate characterization 750:775 conjugate characterization 750:775 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 7 1 theme conjugate 1044:1052 arg1 composition 1069:1079 conjugate monosaccharide composition 1044:1079 conjugate monosaccharide composition 1044:1079 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 5 2 theme vaccine 663:669 arg1 development 610:620 development 610:620 development 610:620 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 5 2 theme vaccine 663:669 arg1 process 598:604 process 598:604 process 598:604 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 7 3 theme conjugation 1095:1105 arg1 degree 1085:1090 degree 1085:1090 degree of conjugation 1085:1105 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 7 3 theme conjugation 1095:1105 arg1 composition 1069:1079 conjugate monosaccharide composition 1044:1079 conjugate monosaccharide composition 1044:1079 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 5 4 theme 15-valent 629:637 arg1 PCV15 672:676 PCV15 672:676 PCV15 672:676 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 5 4 theme 15-valent 629:637 arg1 vaccine 663:669 our 15-valent pneumococcal conjugated vaccine 625:669 our 15-valent pneumococcal conjugated vaccine (PCV15) 625:677 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 7 5 theme liquid 980:985 arg1 RP-UPLC 1003:1009 RP-UPLC 1003:1009 RP-UPLC 1003:1009 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 7 5 theme liquid 980:985 arg1 chromatography 987:1000 reversed-phase ultra-performance liquid chromatography 947:1000 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method 945:1017 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 1 6 theme illnesses 160:168 arg1 range 151:155 a range 149:155 a range of illnesses 149:168 Streptococcus pneumoniae is a highly invasive bacterial pathogen that can cause a range of illnesses. 37402017 8 7 theme pneumococcal 1205:1216 arg1 conjugate 1218:1226 the pneumococcal conjugate and conjugation process 1201:1250 conjugate 1218:1226 The collective information obtained by these chromatographic analysis provided insights into the pneumococcal conjugate and conjugation process. 37402017 5 8 theme pneumococcal 639:650 arg1 PCV15 672:676 PCV15 672:676 PCV15 672:676 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 5 8 theme pneumococcal 639:650 arg1 vaccine 663:669 our 15-valent pneumococcal conjugated vaccine 625:669 our 15-valent pneumococcal conjugated vaccine (PCV15) 625:677 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 7 9 theme chromatography 987:1000 arg1 method 1012:1017 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method 945:1017 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method 945:1017 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 5 10 theme conjugated 652:661 arg1 PCV15 672:676 PCV15 672:676 PCV15 672:676 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 5 10 theme conjugated 652:661 arg1 vaccine 663:669 our 15-valent pneumococcal conjugated vaccine 625:669 our 15-valent pneumococcal conjugated vaccine (PCV15) 625:677 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 7 11 theme reversed-phase 947:960 arg1 RP-UPLC 1003:1009 RP-UPLC 1003:1009 RP-UPLC 1003:1009 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 7 11 theme reversed-phase 947:960 arg1 chromatography 987:1000 reversed-phase ultra-performance liquid chromatography 947:1000 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method 945:1017 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 1 12 theme Streptococcus 69:81 arg1 pneumoniae 83:92 Streptococcus pneumoniae 69:92 Streptococcus pneumoniae 69:92 Streptococcus pneumoniae is a highly invasive bacterial pathogen that can cause a range of illnesses. 37402017 1 12 theme Streptococcus 69:81 arg1 pathogen 125:132 a highly invasive bacterial pathogen 97:132 a highly invasive bacterial pathogen that can cause a range of illnesses 97:168 Streptococcus pneumoniae is a highly invasive bacterial pathogen that can cause a range of illnesses. 37402017 3 13 theme few 337:339 arg1 serotypes 347:355 a few other serotypes 335:355 a few other serotypes 335:355 Pneumococcal CPS serotype 7F along with a few other serotypes is more invasive and likely to cause IPD. 37402017 4 14 theme vaccine 442:448 arg1 development 450:460 pneumococcal vaccine development 429:460 pneumococcal vaccine development 429:460 Therefore, 7F is a target for pneumococcal vaccine development, and is included in the two recently approved multi-valent pneumococcal conjugated vaccines, i.e. VAXNEUVANCE and PREVNAR 20. 37402017 7 15 theme ultra-performance 962:978 arg1 RP-UPLC 1003:1009 RP-UPLC 1003:1009 RP-UPLC 1003:1009 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 7 15 theme ultra-performance 962:978 arg1 chromatography 987:1000 reversed-phase ultra-performance liquid chromatography 947:1000 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method 945:1017 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 3 16 theme other 341:345 arg1 serotypes 347:355 a few other serotypes 335:355 a few other serotypes 335:355 Pneumococcal CPS serotype 7F along with a few other serotypes is more invasive and likely to cause IPD. 37402017 6 17 theme chromatography 795:808 arg1 method 816:821 A size-exclusion chromatography (SEC) method 778:821 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections 778:879 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. 37402017 6 18 theme size-exclusion 780:793 arg1 SEC 811:813 SEC 811:813 SEC 811:813 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. 37402017 6 18 theme size-exclusion 780:793 arg1 chromatography 795:808 size-exclusion chromatography 780:808 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections 778:879 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. 37402017 7 19 theme composition 1069:1079 arg1 analysis 1032:1039 analysis 1032:1039 analysis of conjugate monosaccharide composition and degree of conjugation 1032:1105 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 8 20 theme conjugation 1232:1242 arg1 process 1244:1250 the pneumococcal conjugate and conjugation process 1201:1250 process 1244:1250 The collective information obtained by these chromatographic analysis provided insights into the pneumococcal conjugate and conjugation process. 37402017 4 21 theme conjugated 534:543 arg1 vaccines 545:552 the two recently approved multi-valent pneumococcal conjugated vaccines 482:552 the two recently approved multi-valent pneumococcal conjugated vaccines 482:552 Therefore, 7F is a target for pneumococcal vaccine development, and is included in the two recently approved multi-valent pneumococcal conjugated vaccines, i.e. VAXNEUVANCE and PREVNAR 20. 37402017 6 22 theme conformation 922:933 arg1 analysis 935:942 conformation analysis 922:942 conformation analysis 922:942 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. 37402017 6 23 theme refractive 853:862 arg1 index 864:868 refractive index 853:868 refractive index 853:868 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. 37402017 0 24 theme serotype 33:40 arg1 Characterization 0:15 Characterization 0:15 Characterization of pneumococcal serotype 0:40 Characterization of pneumococcal serotype 7F in vaccine conjugation. 37402017 4 25 theme pneumococcal 521:532 arg1 vaccines 545:552 the two recently approved multi-valent pneumococcal conjugated vaccines 482:552 the two recently approved multi-valent pneumococcal conjugated vaccines 482:552 Therefore, 7F is a target for pneumococcal vaccine development, and is included in the two recently approved multi-valent pneumococcal conjugated vaccines, i.e. VAXNEUVANCE and PREVNAR 20. 37402017 1 26 theme invasive 106:113 arg1 pneumoniae 83:92 Streptococcus pneumoniae 69:92 Streptococcus pneumoniae 69:92 Streptococcus pneumoniae is a highly invasive bacterial pathogen that can cause a range of illnesses. 37402017 1 26 theme invasive 106:113 arg1 pathogen 125:132 a highly invasive bacterial pathogen 97:132 a highly invasive bacterial pathogen that can cause a range of illnesses 97:168 Streptococcus pneumoniae is a highly invasive bacterial pathogen that can cause a range of illnesses. 37402017 0 27 theme pneumococcal 20:31 arg1 serotype 33:40 pneumococcal serotype 20:40 pneumococcal serotype 20:40 Characterization of pneumococcal serotype 7F in vaccine conjugation. 37402017 5 28 theme chromatographic 680:694 arg1 methods 696:702 chromatographic methods 680:702 chromatographic methods 680:702 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 1 29 theme bacterial 115:123 arg1 pneumoniae 83:92 Streptococcus pneumoniae 69:92 Streptococcus pneumoniae 69:92 Streptococcus pneumoniae is a highly invasive bacterial pathogen that can cause a range of illnesses. 37402017 1 29 theme bacterial 115:123 arg1 pathogen 125:132 a highly invasive bacterial pathogen 97:132 a highly invasive bacterial pathogen that can cause a range of illnesses 97:168 Streptococcus pneumoniae is a highly invasive bacterial pathogen that can cause a range of illnesses. 37402017 4 30 dep VAXNEUVANCE 560:570 arg1 i.e. 555:558 i.e. 555:558 i.e. 555:558 Therefore, 7F is a target for pneumococcal vaccine development, and is included in the two recently approved multi-valent pneumococcal conjugated vaccines, i.e. VAXNEUVANCE and PREVNAR 20. 37402017 2 31 theme capsular 184:191 arg1 CPS 210:212 CPS 210:212 CPS 210:212 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 2 31 theme capsular 184:191 arg1 polysaccharides 193:207 Pneumococcal capsular polysaccharides 171:207 Pneumococcal capsular polysaccharides (CPS) 171:213 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 2 31 theme capsular 184:191 arg1 factors 238:244 the main virulence factors 219:244 the main virulence factors that causes invasive pneumococcal disease (IPD) 219:292 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 7 32 theme degree 1085:1090 arg1 analysis 1032:1039 analysis 1032:1039 analysis of conjugate monosaccharide composition and degree of conjugation 1032:1105 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 2 33 theme Pneumococcal 171:182 arg1 CPS 210:212 CPS 210:212 CPS 210:212 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 2 33 theme Pneumococcal 171:182 arg1 polysaccharides 193:207 Pneumococcal capsular polysaccharides 171:207 Pneumococcal capsular polysaccharides (CPS) 171:213 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 2 33 theme Pneumococcal 171:182 arg1 factors 238:244 the main virulence factors 219:244 the main virulence factors that causes invasive pneumococcal disease (IPD) 219:292 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 2 34 theme virulence 228:236 arg1 factors 238:244 the main virulence factors 219:244 the main virulence factors that causes invasive pneumococcal disease (IPD) 219:292 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 2 34 theme virulence 228:236 arg1 polysaccharides 193:207 Pneumococcal capsular polysaccharides 171:207 Pneumococcal capsular polysaccharides (CPS) 171:213 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 5 35 theme 7F 728:729 arg1 polysaccharide 731:744 7F polysaccharide 728:744 7F polysaccharide 728:744 To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. 37402017 3 36 theme CPS 308:310 arg1 7F 321:322 Pneumococcal CPS serotype 7F 295:322 Pneumococcal CPS serotype 7F along with a few other serotypes 295:355 Pneumococcal CPS serotype 7F along with a few other serotypes is more invasive and likely to cause IPD. 37402017 2 37 theme main 223:226 arg1 factors 238:244 the main virulence factors 219:244 the main virulence factors that causes invasive pneumococcal disease (IPD) 219:292 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 2 37 theme main 223:226 arg1 polysaccharides 193:207 Pneumococcal capsular polysaccharides 171:207 Pneumococcal capsular polysaccharides (CPS) 171:213 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 0 38 theme vaccine 48:54 arg1 conjugation 56:66 vaccine conjugation 48:66 vaccine conjugation 48:66 Characterization of pneumococcal serotype 7F in vaccine conjugation. 37402017 4 39 theme multi-valent 508:519 arg1 vaccines 545:552 the two recently approved multi-valent pneumococcal conjugated vaccines 482:552 the two recently approved multi-valent pneumococcal conjugated vaccines 482:552 Therefore, 7F is a target for pneumococcal vaccine development, and is included in the two recently approved multi-valent pneumococcal conjugated vaccines, i.e. VAXNEUVANCE and PREVNAR 20. 37402017 3 40 theme serotype 312:319 arg1 7F 321:322 Pneumococcal CPS serotype 7F 295:322 Pneumococcal CPS serotype 7F along with a few other serotypes 295:355 Pneumococcal CPS serotype 7F along with a few other serotypes is more invasive and likely to cause IPD. 37402017 6 41 theme light 832:836 arg1 scattering 838:847 light scattering 832:847 light scattering 832:847 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. 37402017 6 42 dep UV 828:829 arg1 detections 870:879 detections 870:879 detections 870:879 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. 37402017 4 43 theme pneumococcal 429:440 arg1 development 450:460 pneumococcal vaccine development 429:460 pneumococcal vaccine development 429:460 Therefore, 7F is a target for pneumococcal vaccine development, and is included in the two recently approved multi-valent pneumococcal conjugated vaccines, i.e. VAXNEUVANCE and PREVNAR 20. 37402017 7 44 used used 1023:1026 arg2 method 1012:1017 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method 945:1017 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method 945:1017 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 4 45 theme approved 499:506 arg1 vaccines 545:552 the two recently approved multi-valent pneumococcal conjugated vaccines 482:552 the two recently approved multi-valent pneumococcal conjugated vaccines 482:552 Therefore, 7F is a target for pneumococcal vaccine development, and is included in the two recently approved multi-valent pneumococcal conjugated vaccines, i.e. VAXNEUVANCE and PREVNAR 20. 37402017 8 46 theme chromatographic 1153:1167 arg1 analysis 1169:1176 these chromatographic analysis 1147:1176 these chromatographic analysis 1147:1176 The collective information obtained by these chromatographic analysis provided insights into the pneumococcal conjugate and conjugation process. 37402017 2 47 theme pneumococcal 267:278 arg1 IPD 289:291 IPD 289:291 IPD 289:291 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 2 47 theme pneumococcal 267:278 arg1 disease 280:286 invasive pneumococcal disease 258:286 invasive pneumococcal disease (IPD) 258:292 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 3 48 theme Pneumococcal 295:306 arg1 7F 321:322 Pneumococcal CPS serotype 7F 295:322 Pneumococcal CPS serotype 7F along with a few other serotypes 295:355 Pneumococcal CPS serotype 7F along with a few other serotypes is more invasive and likely to cause IPD. 37402017 2 49 theme invasive 258:265 arg1 IPD 289:291 IPD 289:291 IPD 289:291 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 2 49 theme invasive 258:265 arg1 disease 280:286 invasive pneumococcal disease 258:286 invasive pneumococcal disease (IPD) 258:292 Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). 37402017 6 50 with method 816:821 arg1 UV 828:829 UV 828:829 UV 828:829 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. 37402017 6 50 with method 816:821 arg1 scattering 838:847 light scattering 832:847 light scattering 832:847 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. 37402017 6 50 with method 816:821 arg1 index 864:868 refractive index 853:868 refractive index 853:868 A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. 37402017 7 51 theme monosaccharide 1054:1067 arg1 composition 1069:1079 conjugate monosaccharide composition 1044:1079 conjugate monosaccharide composition 1044:1079 A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. 37402017 3 52 theme a 335:335 arg1 serotypes 347:355 a few other serotypes 335:355 a few other serotypes 335:355 Pneumococcal CPS serotype 7F along with a few other serotypes is more invasive and likely to cause IPD. 37402017 8 53 theme collective 1112:1121 arg1 information 1123:1133 The collective information 1108:1133 The collective information obtained by these chromatographic analysis 1108:1176 The collective information obtained by these chromatographic analysis provided insights into the pneumococcal conjugate and conjugation process. 36837641 2 0 theme cell 456:459 arg1 membranes 330:338 mammalian and bacterial membranes 306:338 mammalian and bacterial membranes 306:338 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 2 0 theme cell 456:459 arg1 frequencies 430:440 the conserved frequencies 416:440 the conserved frequencies of a specific cell 416:459 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 1 1 theme membranes 145:153 arg1 properties 122:131 the mechanical properties 107:131 the mechanical properties of cellular membranes 107:153 A growing body of work has linked key biological activities to the mechanical properties of cellular membranes, and as a means of identification. 36837641 2 2 from spectra 272:278 arg1 region 295:300 the low-THz region 283:300 the low-THz region 283:300 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 2 3 theme specific 447:454 arg1 cell 456:459 a specific cell 445:459 a specific cell 445:459 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 5 4 theme biologically-relevant 988:1008 arg1 structures 1020:1029 numerous biologically-relevant nanoscale structures 979:1029 numerous biologically-relevant nanoscale structures 979:1029 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 5 5 theme other 827:831 arg1 structures 844:853 other biological structures 827:853 other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) 827:924 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 2 6 theme bacterial 320:328 arg1 membranes 330:338 mammalian and bacterial membranes 306:338 mammalian and bacterial membranes 306:338 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 2 7 theme vibrational 260:270 arg1 spectra 272:278 the vibrational spectra 256:278 the vibrational spectra in the low-THz region 256:300 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 5 8 theme amyloid 862:868 arg1 fibers 870:875 amyloid fibers 862:875 amyloid fibers 862:875 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 3 9 theme vibrational 505:515 arg1 spectra 517:523 the vibrational spectra 501:523 the vibrational spectra 501:523 We find that asymmetry does not impact the vibrational spectra, and the impact of sterols depends on the mobility of the components of the membrane. 36837641 2 10 theme composition 392:402 arg1 effect 359:364 the effect 355:364 the effect of membrane asymmetry and composition 355:402 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 1 11 theme work 62:65 arg1 body 54:57 A growing body 44:57 A growing body of work 44:65 A growing body of work has linked key biological activities to the mechanical properties of cellular membranes, and as a means of identification. 36837641 2 12 theme membrane 369:376 arg1 asymmetry 378:386 membrane asymmetry 369:386 membrane asymmetry 369:386 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 2 13 theme low-THz 287:293 arg1 region 295:300 the low-THz region 283:300 the low-THz region 283:300 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 0 14 theme Low-THz 0:6 arg1 Vibrations 8:17 Low-THz Vibrations 0:17 Low-THz Vibrations of Biological Membranes 0:41 Low-THz Vibrations of Biological Membranes. 36837641 1 15 theme key 78:80 arg1 activities 93:102 key biological activities 78:102 key biological activities 78:102 A growing body of work has linked key biological activities to the mechanical properties of cellular membranes, and as a means of identification. 36837641 0 16 theme Biological 22:31 arg1 Membranes 33:41 Biological Membranes 22:41 Biological Membranes 22:41 Low-THz Vibrations of Biological Membranes. 36837641 4 17 used used 658:661 arg2 spectra 643:649 vibrational spectra 631:649 vibrational spectra 631:649 We demonstrate that vibrational spectra can be used to distinguish between membranes and, therefore, could be used in identification of different organisms. 36837641 1 18 theme biological 82:91 arg1 activities 93:102 key biological activities 78:102 key biological activities 78:102 A growing body of work has linked key biological activities to the mechanical properties of cellular membranes, and as a means of identification. 36837641 4 19 theme organisms 757:765 arg1 identification 729:742 identification 729:742 identification of different organisms 729:765 We demonstrate that vibrational spectra can be used to distinguish between membranes and, therefore, could be used in identification of different organisms. 36837641 5 20 theme protein-ligand 899:912 arg1 structures 914:923 protein-ligand structures 899:923 protein-ligand structures 899:923 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 5 21 theme structures 1020:1029 arg1 vibrations 965:974 vibrations 965:974 vibrations of numerous biologically-relevant nanoscale structures 965:1029 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 5 22 theme biological 833:842 arg1 structures 844:853 other biological structures 827:853 other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) 827:924 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 4 23 used used 721:724 arg2 spectra 643:649 vibrational spectra 631:649 vibrational spectra 631:649 We demonstrate that vibrational spectra can be used to distinguish between membranes and, therefore, could be used in identification of different organisms. 36837641 1 24 theme identification 174:187 arg1 means 165:169 a means 163:169 a means of identification 163:187 A growing body of work has linked key biological activities to the mechanical properties of cellular membranes, and as a means of identification. 36837641 3 25 theme sterols 544:550 arg1 impact 534:539 the impact 530:539 the impact of sterols 530:550 We find that asymmetry does not impact the vibrational spectra, and the impact of sterols depends on the mobility of the components of the membrane. 36837641 0 26 theme Membranes 33:41 arg1 Vibrations 8:17 Low-THz Vibrations 0:17 Low-THz Vibrations of Biological Membranes 0:41 Low-THz Vibrations of Biological Membranes. 36837641 5 27 dep structures 844:853 arg1 polysaccharides 878:892 polysaccharides 878:892 polysaccharides 878:892 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 5 27 dep structures 844:853 arg1 fibers 870:875 amyloid fibers 862:875 amyloid fibers 862:875 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 5 27 dep structures 844:853 arg1 structures 914:923 protein-ligand structures 899:923 protein-ligand structures 899:923 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 4 28 theme different 747:755 arg1 organisms 757:765 different organisms 747:765 different organisms 747:765 We demonstrate that vibrational spectra can be used to distinguish between membranes and, therefore, could be used in identification of different organisms. 36837641 2 29 theme asymmetry 378:386 arg1 effect 359:364 the effect 355:364 the effect of membrane asymmetry and composition 355:402 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 1 30 attach linked 71:76 arg2 body 54:57 A growing body 44:57 A growing body of work 44:65 A growing body of work has linked key biological activities to the mechanical properties of cellular membranes, and as a means of identification. 36837641 1 30 attach linked 71:76 arg1 properties 122:131 the mechanical properties 107:131 the mechanical properties of cellular membranes 107:153 A growing body of work has linked key biological activities to the mechanical properties of cellular membranes, and as a means of identification. 36837641 3 31 theme components 583:592 arg1 mobility 567:574 the mobility 563:574 the mobility of the components of the membrane 563:608 We find that asymmetry does not impact the vibrational spectra, and the impact of sterols depends on the mobility of the components of the membrane. 36837641 2 32 theme conserved 420:428 arg1 frequencies 430:440 the conserved frequencies 416:440 the conserved frequencies of a specific cell 416:459 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 5 33 dep fibers 870:875 arg1 e.g. 856:859 e.g. 856:859 e.g. 856:859 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 2 34 theme mammalian 306:314 arg1 membranes 330:338 mammalian and bacterial membranes 306:338 mammalian and bacterial membranes 306:338 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 1 35 theme growing 46:52 arg1 body 54:57 A growing body 44:57 A growing body of work 44:65 A growing body of work has linked key biological activities to the mechanical properties of cellular membranes, and as a means of identification. 36837641 5 36 theme numerous 979:986 arg1 structures 1020:1029 numerous biologically-relevant nanoscale structures 979:1029 numerous biologically-relevant nanoscale structures 979:1029 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 1 37 theme mechanical 111:120 arg1 properties 122:131 the mechanical properties 107:131 the mechanical properties of cellular membranes 107:153 A growing body of work has linked key biological activities to the mechanical properties of cellular membranes, and as a means of identification. 36837641 4 38 dep used 658:661 arg1 used 721:724 used 721:724 could be used in identification of different organisms 712:765 We demonstrate that vibrational spectra can be used to distinguish between membranes and, therefore, could be used in identification of different organisms. 36837641 3 39 theme membrane 601:608 arg1 components 583:592 the components 579:592 the components of the membrane 579:608 We find that asymmetry does not impact the vibrational spectra, and the impact of sterols depends on the mobility of the components of the membrane. 36837641 5 40 theme nanoscale 1010:1018 arg1 structures 1020:1029 numerous biologically-relevant nanoscale structures 979:1029 numerous biologically-relevant nanoscale structures 979:1029 The method presented, here, can be immediately extended to other biological structures (e.g., amyloid fibers, polysaccharides, and protein-ligand structures) in order to fingerprint and understand vibrations of numerous biologically-relevant nanoscale structures. 36837641 4 41 theme vibrational 631:641 arg1 spectra 643:649 vibrational spectra 631:649 vibrational spectra 631:649 We demonstrate that vibrational spectra can be used to distinguish between membranes and, therefore, could be used in identification of different organisms. 36837641 2 42 theme computational 209:221 arg1 approach 223:230 a computational approach 207:230 a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell 207:459 Here, we present a computational approach to simulate and compare the vibrational spectra in the low-THz region for mammalian and bacterial membranes, investigating the effect of membrane asymmetry and composition, as well as the conserved frequencies of a specific cell. 36837641 1 43 theme cellular 136:143 arg1 membranes 145:153 cellular membranes 136:153 cellular membranes 136:153 A growing body of work has linked key biological activities to the mechanical properties of cellular membranes, and as a means of identification. 35868282 6 0 theme gut 895:897 arg1 microbiota 899:908 gut microbiota 895:908 gut microbiota 895:908 Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. 35868282 5 1 dep bacteria 794:801 arg1 such 804:807 such 804:807 such 804:807 Moreover, the relative abundance of beneficial bacteria (such as Lactococcus and Bacteroides) was improved during colonic fermentation. 35868282 4 2 theme p-hydroxybenzoic 651:666 arg1 acid 668:671 p-hydroxybenzoic acid 651:671 p-hydroxybenzoic acid 651:671 About 49 polyphenols and metabolites including quercetin, vanillin, catechin and p-hydroxybenzoic acid were identified, and possible biotransformation pathways were postulated. 35868282 7 3 theme gastrointestinal 1217:1232 arg1 health 1246:1251 gastrointestinal and colonic health 1217:1251 gastrointestinal and colonic health 1217:1251 These findings indicated that polyphenols in mung bean coat potentially contributed to gastrointestinal and colonic health. 35868282 2 4 theme polyphenols 320:330 arg1 release 309:315 the release 305:315 the release of polyphenols from mung bean coat and their bioactivities 305:374 In this study,in vitro simulated digestion and colonic fermentation were performed to investigate the release of polyphenols from mung bean coat and their bioactivities. 35868282 6 5 theme microbiota 1082:1091 arg1 composition 1063:1073 the composition 1059:1073 the composition of gut microbiota 1059:1091 Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. 35868282 2 6 theme colonic 254:260 arg1 fermentation 262:273 colonic fermentation 254:273 colonic fermentation 254:273 In this study,in vitro simulated digestion and colonic fermentation were performed to investigate the release of polyphenols from mung bean coat and their bioactivities. 35868282 4 7 theme biotransformation 703:719 arg1 pathways 721:728 possible biotransformation pathways 694:728 possible biotransformation pathways 694:728 About 49 polyphenols and metabolites including quercetin, vanillin, catechin and p-hydroxybenzoic acid were identified, and possible biotransformation pathways were postulated. 35868282 6 8 theme catabolic 972:980 arg1 metabolites 982:992 their catabolic metabolites 966:992 their catabolic metabolites 966:992 Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. 35868282 0 9 theme gut 74:76 arg1 microbiota 78:87 gut microbiota 74:87 gut microbiota 74:87 Catabolism of polyphenols released from mung bean coat and its effects on gut microbiota during in vitro simulated digestion and colonic fermentation. 35868282 6 10 from fiber 1013:1017 arg1 coat 1032:1035 mung bean coat 1022:1035 mung bean coat 1022:1035 Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. 35868282 3 11 theme higher 513:518 arg1 capacities 532:541 higher antioxidant capacities 513:541 higher antioxidant capacities (DPPH, ORAC, FRAP assays) 513:567 Polyphenols released by colonic fermentation were much higher than those released by digestion and reached a peak at 12 h, resulting in higher antioxidant capacities (DPPH, ORAC, FRAP assays). 35868282 0 12 theme in 96:97 arg1 digestion 115:123 in vitro simulated digestion 96:123 in vitro simulated digestion 96:123 Catabolism of polyphenols released from mung bean coat and its effects on gut microbiota during in vitro simulated digestion and colonic fermentation. 35868282 0 13 from bean 45:48 arg1 microbiota 78:87 gut microbiota 74:87 gut microbiota 74:87 Catabolism of polyphenols released from mung bean coat and its effects on gut microbiota during in vitro simulated digestion and colonic fermentation. 35868282 1 14 theme bean 156:159 arg1 source 176:181 a good source 169:181 a good source of dietary polyphenols 169:204 Mung bean coat is a good source of dietary polyphenols. 35868282 1 14 theme bean 156:159 arg1 coat 161:164 Mung bean coat 151:164 Mung bean coat 151:164 Mung bean coat is a good source of dietary polyphenols. 35868282 2 15 theme simulated 230:238 arg1 digestion 240:248 in vitro simulated digestion 221:248 in vitro simulated digestion 221:248 In this study,in vitro simulated digestion and colonic fermentation were performed to investigate the release of polyphenols from mung bean coat and their bioactivities. 35868282 6 16 theme gut 1078:1080 arg1 microbiota 1082:1091 gut microbiota 1078:1091 gut microbiota 1078:1091 Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. 35868282 7 17 theme bean 1180:1183 arg1 coat 1185:1188 mung bean coat 1175:1188 mung bean coat 1175:1188 These findings indicated that polyphenols in mung bean coat potentially contributed to gastrointestinal and colonic health. 35868282 4 18 theme possible 694:701 arg1 pathways 721:728 possible biotransformation pathways 694:728 possible biotransformation pathways 694:728 About 49 polyphenols and metabolites including quercetin, vanillin, catechin and p-hydroxybenzoic acid were identified, and possible biotransformation pathways were postulated. 35868282 7 19 from polyphenols 1160:1170 arg1 coat 1185:1188 mung bean coat 1175:1188 mung bean coat 1175:1188 These findings indicated that polyphenols in mung bean coat potentially contributed to gastrointestinal and colonic health. 35868282 3 20 theme colonic 401:407 arg1 fermentation 409:420 colonic fermentation 401:420 colonic fermentation 401:420 Polyphenols released by colonic fermentation were much higher than those released by digestion and reached a peak at 12 h, resulting in higher antioxidant capacities (DPPH, ORAC, FRAP assays). 35868282 5 21 theme beneficial 783:792 arg1 bacteria 794:801 beneficial bacteria 783:801 beneficial bacteria (such as Lactococcus and Bacteroides) 783:839 Moreover, the relative abundance of beneficial bacteria (such as Lactococcus and Bacteroides) was improved during colonic fermentation. 35868282 2 22 dep in 221:222 arg1 vitro 224:228 vitro 224:228 vitro 224:228 In this study,in vitro simulated digestion and colonic fermentation were performed to investigate the release of polyphenols from mung bean coat and their bioactivities. 35868282 5 23 theme bacteria 794:801 arg1 abundance 770:778 the relative abundance 757:778 the relative abundance of beneficial bacteria (such as Lactococcus and Bacteroides) 757:839 Moreover, the relative abundance of beneficial bacteria (such as Lactococcus and Bacteroides) was improved during colonic fermentation. 35868282 0 24 theme simulated 105:113 arg1 digestion 115:123 in vitro simulated digestion 96:123 in vitro simulated digestion 96:123 Catabolism of polyphenols released from mung bean coat and its effects on gut microbiota during in vitro simulated digestion and colonic fermentation. 35868282 3 25 theme antioxidant 520:530 arg1 capacities 532:541 higher antioxidant capacities 513:541 higher antioxidant capacities (DPPH, ORAC, FRAP assays) 513:567 Polyphenols released by colonic fermentation were much higher than those released by digestion and reached a peak at 12 h, resulting in higher antioxidant capacities (DPPH, ORAC, FRAP assays). 35868282 1 26 theme good 171:174 arg1 source 176:181 a good source 169:181 a good source of dietary polyphenols 169:204 Mung bean coat is a good source of dietary polyphenols. 35868282 1 26 theme good 171:174 arg1 coat 161:164 Mung bean coat 151:164 Mung bean coat 151:164 Mung bean coat is a good source of dietary polyphenols. 35868282 0 27 theme polyphenols 14:24 arg1 Catabolism 0:9 Catabolism 0:9 Catabolism of polyphenols 0:24 Catabolism of polyphenols released from mung bean coat and its effects on gut microbiota during in vitro simulated digestion and colonic fermentation. 35868282 6 28 theme released 941:948 arg1 polyphenols 950:960 the released polyphenols 937:960 the released polyphenols 937:960 Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. 35868282 1 29 theme Mung 151:154 arg1 source 176:181 a good source 169:181 a good source of dietary polyphenols 169:204 Mung bean coat is a good source of dietary polyphenols. 35868282 1 29 theme Mung 151:154 arg1 coat 161:164 Mung bean coat 151:164 Mung bean coat 151:164 Mung bean coat is a good source of dietary polyphenols. 35868282 0 30 from effects 63:69 arg1 microbiota 78:87 gut microbiota 74:87 gut microbiota 74:87 Catabolism of polyphenols released from mung bean coat and its effects on gut microbiota during in vitro simulated digestion and colonic fermentation. 35868282 6 31 theme bean 1027:1030 arg1 coat 1032:1035 mung bean coat 1022:1035 mung bean coat 1022:1035 Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. 35868282 0 32 dep in 96:97 arg1 vitro 99:103 vitro 99:103 vitro 99:103 Catabolism of polyphenols released from mung bean coat and its effects on gut microbiota during in vitro simulated digestion and colonic fermentation. 35868282 0 33 dep bean 45:48 arg1 coat 50:53 coat 50:53 coat 50:53 Catabolism of polyphenols released from mung bean coat and its effects on gut microbiota during in vitro simulated digestion and colonic fermentation. 35868282 1 34 theme dietary 186:192 arg1 polyphenols 194:204 dietary polyphenols 186:204 dietary polyphenols 186:204 Mung bean coat is a good source of dietary polyphenols. 35868282 5 35 theme relative 761:768 arg1 abundance 770:778 the relative abundance 757:778 the relative abundance of beneficial bacteria (such as Lactococcus and Bacteroides) 757:839 Moreover, the relative abundance of beneficial bacteria (such as Lactococcus and Bacteroides) was improved during colonic fermentation. 35868282 6 36 theme mung 1022:1025 arg1 bean 1027:1030 mung bean 1022:1030 mung bean coat 1022:1035 Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. 35868282 2 37 from coat 347:350 arg1 release 309:315 the release 305:315 the release of polyphenols from mung bean coat and their bioactivities 305:374 In this study,in vitro simulated digestion and colonic fermentation were performed to investigate the release of polyphenols from mung bean coat and their bioactivities. 35868282 6 38 theme SCFAs 1123:1127 arg1 synthesis 1110:1118 the synthesis 1106:1118 the synthesis of SCFAs 1106:1127 Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. 35868282 0 39 theme colonic 129:135 arg1 fermentation 137:148 colonic fermentation 129:148 colonic fermentation 129:148 Catabolism of polyphenols released from mung bean coat and its effects on gut microbiota during in vitro simulated digestion and colonic fermentation. 35868282 2 40 from bioactivities 362:374 arg1 release 309:315 the release 305:315 the release of polyphenols from mung bean coat and their bioactivities 305:374 In this study,in vitro simulated digestion and colonic fermentation were performed to investigate the release of polyphenols from mung bean coat and their bioactivities. 35868282 3 41 theme FRAP 556:559 arg1 assays 561:566 FRAP assays 556:566 FRAP assays 556:566 Polyphenols released by colonic fermentation were much higher than those released by digestion and reached a peak at 12 h, resulting in higher antioxidant capacities (DPPH, ORAC, FRAP assays). 35868282 3 41 theme FRAP 556:559 arg1 DPPH 544:547 DPPH 544:547 DPPH 544:547 Polyphenols released by colonic fermentation were much higher than those released by digestion and reached a peak at 12 h, resulting in higher antioxidant capacities (DPPH, ORAC, FRAP assays). 35868282 1 42 theme polyphenols 194:204 arg1 source 176:181 a good source 169:181 a good source of dietary polyphenols 169:204 Mung bean coat is a good source of dietary polyphenols. 35868282 1 42 theme polyphenols 194:204 arg1 coat 161:164 Mung bean coat 151:164 Mung bean coat 151:164 Mung bean coat is a good source of dietary polyphenols. 35868282 2 43 theme in 221:222 arg1 digestion 240:248 in vitro simulated digestion 221:248 in vitro simulated digestion 221:248 In this study,in vitro simulated digestion and colonic fermentation were performed to investigate the release of polyphenols from mung bean coat and their bioactivities. 35868282 3 44 dep capacities 532:541 arg1 ORAC 550:553 ORAC 550:553 ORAC 550:553 Polyphenols released by colonic fermentation were much higher than those released by digestion and reached a peak at 12 h, resulting in higher antioxidant capacities (DPPH, ORAC, FRAP assays). 35868282 3 44 dep capacities 532:541 arg1 assays 561:566 FRAP assays 556:566 FRAP assays 556:566 Polyphenols released by colonic fermentation were much higher than those released by digestion and reached a peak at 12 h, resulting in higher antioxidant capacities (DPPH, ORAC, FRAP assays). 35868282 3 44 dep capacities 532:541 arg1 DPPH 544:547 DPPH 544:547 DPPH 544:547 Polyphenols released by colonic fermentation were much higher than those released by digestion and reached a peak at 12 h, resulting in higher antioxidant capacities (DPPH, ORAC, FRAP assays). 35868282 5 45 theme colonic 861:867 arg1 fermentation 869:880 colonic fermentation 861:880 colonic fermentation 861:880 Moreover, the relative abundance of beneficial bacteria (such as Lactococcus and Bacteroides) was improved during colonic fermentation. 35868282 2 46 theme bean 342:345 arg1 coat 347:350 mung bean coat 337:350 mung bean coat 337:350 In this study,in vitro simulated digestion and colonic fermentation were performed to investigate the release of polyphenols from mung bean coat and their bioactivities. 35868282 6 47 theme dietary 1005:1011 arg1 fiber 1013:1017 dietary fiber 1005:1017 dietary fiber in mung bean coat 1005:1035 Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. 35868282 7 48 theme colonic 1238:1244 arg1 health 1246:1251 gastrointestinal and colonic health 1217:1251 gastrointestinal and colonic health 1217:1251 These findings indicated that polyphenols in mung bean coat potentially contributed to gastrointestinal and colonic health. 35868282 2 49 theme mung 337:340 arg1 bean 342:345 mung bean 337:345 mung bean coat 337:350 In this study,in vitro simulated digestion and colonic fermentation were performed to investigate the release of polyphenols from mung bean coat and their bioactivities. 35868282 7 50 theme mung 1175:1178 arg1 bean 1180:1183 mung bean 1175:1183 mung bean coat 1175:1188 These findings indicated that polyphenols in mung bean coat potentially contributed to gastrointestinal and colonic health. 35200079 5 0 theme micro-dilution 774:787 arg1 susceptibility 795:808 micro-dilution broth susceptibility 774:808 micro-dilution broth susceptibility 774:808 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 1 1 theme essential 169:177 arg1 oils 179:182 essential oils 169:182 essential oils 169:182 Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. 35200079 5 2 theme resazurin 743:751 arg1 microtitre-plate 753:768 resazurin microtitre-plate 743:768 resazurin microtitre-plate 743:768 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 4 3 theme major 587:591 arg1 compound 593:600 the major compound 583:600 the major compound 583:600 In total, twenty-one compounds were quantified by GC-MS with α-pinene as the major compound, followed by α-thujene, trans-verbenol, β-thujone, p-cymene, m-cymene, and sabinene. 35200079 4 3 theme major 587:591 arg1 compounds 531:539 twenty-one compounds 520:539 twenty-one compounds 520:539 In total, twenty-one compounds were quantified by GC-MS with α-pinene as the major compound, followed by α-thujene, trans-verbenol, β-thujone, p-cymene, m-cymene, and sabinene. 35200079 5 4 theme broth 789:793 arg1 susceptibility 795:808 micro-dilution broth susceptibility 774:808 micro-dilution broth susceptibility 774:808 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 4 5 theme twenty-one 520:529 arg1 compound 593:600 the major compound 583:600 the major compound 583:600 In total, twenty-one compounds were quantified by GC-MS with α-pinene as the major compound, followed by α-thujene, trans-verbenol, β-thujone, p-cymene, m-cymene, and sabinene. 35200079 4 5 theme twenty-one 520:529 arg1 compounds 531:539 twenty-one compounds 520:539 twenty-one compounds 520:539 In total, twenty-one compounds were quantified by GC-MS with α-pinene as the major compound, followed by α-thujene, trans-verbenol, β-thujone, p-cymene, m-cymene, and sabinene. 35200079 1 6 theme oils 179:182 arg1 Oleo-gum-resin 130:143 Oleo-gum-resin 130:143 Oleo-gum-resin 130:143 Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. 35200079 1 6 theme oils 179:182 arg1 mixture 158:164 a complex mixture 148:164 a complex mixture of essential oils, polysaccharides, and resin acids 148:216 Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. 35200079 0 7 theme superheated 111:121 arg1 steam 123:127 superheated steam 111:127 superheated steam 111:127 Chemical composition and antimicrobial activity of Boswellia serrata oleo-gum-resin essential oil extracted by superheated steam. 35200079 2 8 theme chemical 289:296 arg1 components 298:307 chemical components 289:307 chemical components 289:307 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 5 9 theme diffusion 732:740 arg1 assays 810:815 disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays 727:815 disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively 727:942 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 6 10 from oleo-gum-resin 1047:1060 arg1 isolation 1015:1023 the isolation 1011:1023 the isolation of essential oil from oleo-gum-resin 1011:1060 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 6 10 from oleo-gum-resin 1047:1060 arg1 oil 1038:1040 essential oil 1028:1040 essential oil from oleo-gum-resin 1028:1060 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 2 11 theme superheated 367:377 arg1 steam 379:383 superheated steam 367:383 superheated steam at various temperatures 367:407 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 6 12 from isolation 1015:1023 arg1 oleo-gum-resin 1047:1060 oleo-gum-resin 1047:1060 oleo-gum-resin 1047:1060 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 6 13 theme antimicrobial 1117:1129 arg1 activity 1131:1138 antimicrobial activity 1117:1138 the recovery of essential oil as well as antimicrobial activity 1076:1138 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 6 14 theme oil 1102:1104 arg1 recovery 1080:1087 the recovery 1076:1087 the recovery of essential oil as well as antimicrobial activity 1076:1138 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 6 14 theme oil 1102:1104 arg1 activity 1131:1138 antimicrobial activity 1117:1138 the recovery of essential oil as well as antimicrobial activity 1076:1138 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 3 15 theme essential 422:430 arg1 yield 436:440 The optimum essential oil yield 410:440 The optimum essential oil yield 410:440 The optimum essential oil yield was obtained at the highest superheated steam temperature (210 °C). 35200079 5 16 theme susceptibility 795:808 arg1 assays 810:815 disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays 727:815 disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively 727:942 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 4 17 with GC-MS 560:564 arg1 α-pinene 571:578 α-pinene 571:578 α-pinene 571:578 In total, twenty-one compounds were quantified by GC-MS with α-pinene as the major compound, followed by α-thujene, trans-verbenol, β-thujone, p-cymene, m-cymene, and sabinene. 35200079 1 18 theme polysaccharides 185:199 arg1 Oleo-gum-resin 130:143 Oleo-gum-resin 130:143 Oleo-gum-resin 130:143 Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. 35200079 1 18 theme polysaccharides 185:199 arg1 mixture 158:164 a complex mixture 148:164 a complex mixture of essential oils, polysaccharides, and resin acids 148:216 Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. 35200079 5 19 theme essential 826:834 arg1 oil 836:838 essential oil 826:838 essential oil extracted at 150 °C and 180 °C 826:869 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 5 20 theme microtitre-plate 753:768 arg1 assays 810:815 disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays 727:815 disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively 727:942 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 5 21 theme antibacterial 892:904 arg1 activity 921:928 the highest antibacterial and antifungal activity 880:928 the highest antibacterial and antifungal activity 880:928 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 0 22 theme Chemical 0:7 arg1 composition 9:19 Chemical composition 0:19 Chemical composition 0:19 Chemical composition and antimicrobial activity of Boswellia serrata oleo-gum-resin essential oil extracted by superheated steam. 35200079 2 23 theme antimicrobial 313:325 arg1 activity 327:334 antimicrobial activity 313:334 antimicrobial activity 313:334 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 6 24 theme essential 1028:1036 arg1 oil 1038:1040 essential oil 1028:1040 essential oil from oleo-gum-resin 1028:1060 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 2 25 theme various 388:394 arg1 temperatures 396:407 various temperatures 388:407 various temperatures 388:407 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 0 26 theme antimicrobial 25:37 arg1 activity 39:46 antimicrobial activity 25:46 antimicrobial activity of Boswellia serrata 25:67 Chemical composition and antimicrobial activity of Boswellia serrata oleo-gum-resin essential oil extracted by superheated steam. 35200079 5 27 dep antibacterial 892:904 arg1 highest 884:890 highest 884:890 highest 884:890 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 1 28 theme resin 206:210 arg1 acids 212:216 resin acids 206:216 resin acids 206:216 Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. 35200079 6 29 theme effective 990:998 arg1 steam 978:982 superheated steam 966:982 superheated steam 966:982 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 6 29 theme effective 990:998 arg1 method 1000:1005 an effective method 987:1005 an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity 987:1138 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 1 30 theme acids 212:216 arg1 Oleo-gum-resin 130:143 Oleo-gum-resin 130:143 Oleo-gum-resin 130:143 Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. 35200079 1 30 theme acids 212:216 arg1 mixture 158:164 a complex mixture 148:164 a complex mixture of essential oils, polysaccharides, and resin acids 148:216 Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. 35200079 3 31 theme oil 432:434 arg1 yield 436:440 The optimum essential oil yield 410:440 The optimum essential oil yield 410:440 The optimum essential oil yield was obtained at the highest superheated steam temperature (210 °C). 35200079 2 32 theme present 241:247 arg1 study 249:253 the present study 237:253 the present study 237:253 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 6 33 theme essential 1092:1100 arg1 oil 1102:1104 essential oil 1092:1104 essential oil 1092:1104 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 3 34 theme highest 462:468 arg1 210 °C 501:506 210 °C 501:506 210 °C 501:506 The optimum essential oil yield was obtained at the highest superheated steam temperature (210 °C). 35200079 3 34 theme highest 462:468 arg1 temperature 488:498 the highest superheated steam temperature 458:498 the highest superheated steam temperature (210 °C) 458:507 The optimum essential oil yield was obtained at the highest superheated steam temperature (210 °C). 35200079 2 35 from temperatures 396:407 arg1 steam 379:383 superheated steam 367:383 superheated steam at various temperatures 367:407 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 3 36 theme superheated 470:480 arg1 210 °C 501:506 210 °C 501:506 210 °C 501:506 The optimum essential oil yield was obtained at the highest superheated steam temperature (210 °C). 35200079 3 36 theme superheated 470:480 arg1 temperature 488:498 the highest superheated steam temperature 458:498 the highest superheated steam temperature (210 °C) 458:507 The optimum essential oil yield was obtained at the highest superheated steam temperature (210 °C). 35200079 0 37 theme serrata 61:67 arg1 composition 9:19 Chemical composition 0:19 Chemical composition 0:19 Chemical composition and antimicrobial activity of Boswellia serrata oleo-gum-resin essential oil extracted by superheated steam. 35200079 0 37 theme serrata 61:67 arg1 activity 39:46 antimicrobial activity 25:46 antimicrobial activity of Boswellia serrata 25:67 Chemical composition and antimicrobial activity of Boswellia serrata oleo-gum-resin essential oil extracted by superheated steam. 35200079 5 38 theme disc 727:730 arg1 diffusion 732:740 disc diffusion 727:740 disc diffusion 727:740 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 0 39 theme Boswellia 51:59 arg1 serrata 61:67 Boswellia serrata 51:67 Boswellia serrata 51:67 Chemical composition and antimicrobial activity of Boswellia serrata oleo-gum-resin essential oil extracted by superheated steam. 35200079 6 40 theme superheated 966:976 arg1 steam 978:982 superheated steam 966:982 superheated steam 966:982 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 6 40 theme superheated 966:976 arg1 method 1000:1005 an effective method 987:1005 an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity 987:1138 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 35200079 2 41 theme oils 349:352 arg1 components 298:307 chemical components 289:307 chemical components 289:307 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 2 41 theme oils 349:352 arg1 activity 327:334 antimicrobial activity 313:334 antimicrobial activity 313:334 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 2 42 from variation 276:284 arg1 components 298:307 chemical components 289:307 chemical components 289:307 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 2 42 from variation 276:284 arg1 activity 327:334 antimicrobial activity 313:334 antimicrobial activity 313:334 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 2 43 theme essential 339:347 arg1 oils 349:352 essential oils 339:352 essential oils extracted by superheated steam at various temperatures 339:407 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 5 44 theme Antimicrobial 687:699 arg1 activity 701:708 Antimicrobial activity 687:708 Antimicrobial activity 687:708 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 1 45 theme complex 150:156 arg1 Oleo-gum-resin 130:143 Oleo-gum-resin 130:143 Oleo-gum-resin 130:143 Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. 35200079 1 45 theme complex 150:156 arg1 mixture 158:164 a complex mixture 148:164 a complex mixture of essential oils, polysaccharides, and resin acids 148:216 Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. 35200079 0 46 theme essential 84:92 arg1 oil 94:96 essential oil 84:96 essential oil extracted by superheated steam 84:127 Chemical composition and antimicrobial activity of Boswellia serrata oleo-gum-resin essential oil extracted by superheated steam. 35200079 3 47 theme steam 482:486 arg1 210 °C 501:506 210 °C 501:506 210 °C 501:506 The optimum essential oil yield was obtained at the highest superheated steam temperature (210 °C). 35200079 3 47 theme steam 482:486 arg1 temperature 488:498 the highest superheated steam temperature 458:498 the highest superheated steam temperature (210 °C) 458:507 The optimum essential oil yield was obtained at the highest superheated steam temperature (210 °C). 35200079 5 48 theme antifungal 910:919 arg1 activity 921:928 the highest antibacterial and antifungal activity 880:928 the highest antibacterial and antifungal activity 880:928 Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. 35200079 3 49 theme optimum 414:420 arg1 yield 436:440 The optimum essential oil yield 410:440 The optimum essential oil yield 410:440 The optimum essential oil yield was obtained at the highest superheated steam temperature (210 °C). 35200079 2 50 theme study 249:253 arg1 objectives 223:232 The objectives 219:232 The objectives of the present study 219:253 The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. 35200079 6 51 theme oil 1038:1040 arg1 isolation 1015:1023 the isolation 1011:1023 the isolation of essential oil from oleo-gum-resin 1011:1060 It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity. 37330081 12 0 theme I/R 1671:1673 arg1 injury 1675:1680 intestinal I/R injury 1660:1680 intestinal I/R injury 1660:1680 This study proves that GL-PPSQ2 is a novel drug candidate for preventing and treating intestinal I/R injury. 37330081 9 1 theme extracellular 1205:1217 arg1 formation 1230:1238 neutrophil extracellular trap (NET) formation 1194:1238 neutrophil extracellular trap (NET) formation 1194:1238 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 37330081 5 2 theme 1.45:2.37:16.46 641:655 arg1 ratio 629:633 a molar ratio 621:633 a molar ratio of 1: 1.45:2.37:16.46 621:655 The monosaccharide composition of GL-PPSQ2 was determined to be composed of fucose, mannose, galactose and glucose with a molar ratio of 1: 1.45:2.37:16.46. 37330081 9 3 theme trap 1219:1222 arg1 formation 1230:1238 neutrophil extracellular trap (NET) formation 1194:1238 neutrophil extracellular trap (NET) formation 1194:1238 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 37330081 7 4 theme survival 872:879 arg1 rate 881:884 the survival rate 868:884 the survival rate 868:884 Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. 37330081 11 5 theme induced 1457:1463 arg1 injury 1470:1475 its induced lung injury 1453:1475 its induced lung injury 1453:1475 GL-PPSQ2 could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. 37330081 8 6 theme oxidative 1071:1079 arg1 stress 1081:1086 oxidative stress 1071:1086 oxidative stress 1071:1086 Meanwhile, GL-PPSQ2 significantly promoted intestinal tight junction, decreased inflammation, oxidative stress and cellular apoptosis in the ileum and lung. 37330081 9 7 theme NET 1225:1227 arg1 formation 1230:1238 neutrophil extracellular trap (NET) formation 1194:1238 neutrophil extracellular trap (NET) formation 1194:1238 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 37330081 10 8 theme citrulline-Histone 1367:1384 arg1 citH3 1390:1394 citH3 1390:1394 citH3 1390:1394 GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. 37330081 10 8 theme citrulline-Histone 1367:1384 arg1 H3 1386:1387 citrulline-Histone H3 1367:1387 citrulline-Histone H3 (citH3) 1367:1395 GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. 37330081 11 9 theme lung 1465:1468 arg1 injury 1470:1475 its induced lung injury 1453:1475 its induced lung injury 1453:1475 GL-PPSQ2 could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. 37330081 4 10 theme O-glycosidic 481:492 arg1 bonds 494:498 O-glycosidic bonds 481:498 O-glycosidic bonds 481:498 We extracted and characterized a novel GLPP, named GL-PPSQ2, which were found to have 18 amino acids and 48 proteins, connected by O-glycosidic bonds. 37330081 7 11 theme pulmonary 960:968 arg1 edema 970:974 pulmonary edema 960:974 pulmonary edema 960:974 Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. 37330081 10 12 theme myeloperoxidase 1341:1355 arg1 expression 1397:1406 NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression 1320:1406 NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression 1320:1406 GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. 37330081 5 13 theme molar 623:627 arg1 ratio 629:633 a molar ratio 621:633 a molar ratio of 1: 1.45:2.37:16.46 621:655 The monosaccharide composition of GL-PPSQ2 was determined to be composed of fucose, mannose, galactose and glucose with a molar ratio of 1: 1.45:2.37:16.46. 37330081 0 14 dep extracellular 136:148 arg1 traps 150:154 traps 150:154 traps 150:154 Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps. 37330081 5 15 theme monosaccharide 505:518 arg1 composition 520:530 The monosaccharide composition 501:530 The monosaccharide composition of GL-PPSQ2 501:542 The monosaccharide composition of GL-PPSQ2 was determined to be composed of fucose, mannose, galactose and glucose with a molar ratio of 1: 1.45:2.37:16.46. 37330081 10 16 theme H3 1386:1387 arg1 expression 1397:1406 NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression 1320:1406 NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression 1320:1406 GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. 37330081 8 17 theme tight 1031:1035 arg1 inflammation 1057:1068 intestinal tight junction, decreased inflammation 1020:1068 inflammation 1057:1068 Meanwhile, GL-PPSQ2 significantly promoted intestinal tight junction, decreased inflammation, oxidative stress and cellular apoptosis in the ileum and lung. 37330081 9 18 theme intestinal 1267:1276 arg1 injury 1282:1287 intestinal I/R injury 1267:1287 intestinal I/R injury 1267:1287 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 37330081 1 19 theme main 215:218 arg1 ingredients 230:240 the main effective ingredients 211:240 the main effective ingredients from G. lucidum 211:256 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 1 19 theme main 215:218 arg1 peptides 191:198 Ganoderma lucidum polysaccharides peptides 157:198 Ganoderma lucidum polysaccharides peptides (GLPP) 157:205 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 0 20 theme lucidum 10:16 arg1 peptides 33:40 Ganoderma lucidum polysaccharide peptides 0:40 Ganoderma lucidum polysaccharide peptides 0:40 Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps. 37330081 12 21 theme intestinal 1660:1669 arg1 injury 1675:1680 intestinal I/R injury 1660:1680 intestinal I/R injury 1660:1680 This study proves that GL-PPSQ2 is a novel drug candidate for preventing and treating intestinal I/R injury. 37330081 8 22 theme intestinal 1020:1029 arg1 inflammation 1057:1068 intestinal tight junction, decreased inflammation 1020:1068 inflammation 1057:1068 Meanwhile, GL-PPSQ2 significantly promoted intestinal tight junction, decreased inflammation, oxidative stress and cellular apoptosis in the ileum and lung. 37330081 1 23 theme effective 220:228 arg1 ingredients 230:240 the main effective ingredients 211:240 the main effective ingredients from G. lucidum 211:256 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 1 23 theme effective 220:228 arg1 peptides 191:198 Ganoderma lucidum polysaccharides peptides 157:198 Ganoderma lucidum polysaccharides peptides (GLPP) 157:205 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 0 24 theme Ganoderma 0:8 arg1 lucidum 10:16 Ganoderma lucidum 0:16 Ganoderma lucidum polysaccharide peptides 0:40 Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps. 37330081 8 25 theme cellular 1092:1099 arg1 apoptosis 1101:1109 cellular apoptosis 1092:1109 cellular apoptosis 1092:1109 Meanwhile, GL-PPSQ2 significantly promoted intestinal tight junction, decreased inflammation, oxidative stress and cellular apoptosis in the ileum and lung. 37330081 7 26 theme pulmonary 932:940 arg1 permeability 942:953 pulmonary permeability 932:953 pulmonary permeability 932:953 Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. 37330081 6 27 theme separation 689:698 arg1 technique 700:708 asymmetric field-flow separation technique 667:708 asymmetric field-flow separation technique 667:708 By using asymmetric field-flow separation technique, GL-PPSQ2 were found to have a highly branched structure. 37330081 8 28 theme decreased 1047:1055 arg1 inflammation 1057:1068 intestinal tight junction, decreased inflammation 1020:1068 inflammation 1057:1068 Meanwhile, GL-PPSQ2 significantly promoted intestinal tight junction, decreased inflammation, oxidative stress and cellular apoptosis in the ileum and lung. 37330081 10 29 theme protein 1333:1339 arg1 MPO 1358:1360 MPO 1358:1360 MPO 1358:1360 GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. 37330081 10 29 theme protein 1333:1339 arg1 myeloperoxidase 1341:1355 NETs-related protein myeloperoxidase 1320:1355 NETs-related protein myeloperoxidase (MPO) 1320:1361 GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. 37330081 3 30 theme antioxidant 304:314 arg1 activities 338:347 anti-inflammatory, antioxidant, and immunoregulatory activities 285:347 anti-inflammatory, antioxidant, and immunoregulatory activities 285:347 Karst with anti-inflammatory, antioxidant, and immunoregulatory activities. 37330081 8 31 theme junction 1037:1044 arg1 inflammation 1057:1068 intestinal tight junction, decreased inflammation 1020:1068 inflammation 1057:1068 Meanwhile, GL-PPSQ2 significantly promoted intestinal tight junction, decreased inflammation, oxidative stress and cellular apoptosis in the ileum and lung. 37330081 6 32 theme field-flow 678:687 arg1 technique 700:708 asymmetric field-flow separation technique 667:708 asymmetric field-flow separation technique 667:708 By using asymmetric field-flow separation technique, GL-PPSQ2 were found to have a highly branched structure. 37330081 0 33 theme polysaccharide 18:31 arg1 peptides 33:40 Ganoderma lucidum polysaccharide peptides 0:40 Ganoderma lucidum polysaccharide peptides 0:40 Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps. 37330081 7 34 theme intestinal 784:793 arg1 ischemia-reperfusion 795:814 intestinal ischemia-reperfusion 784:814 an intestinal ischemia-reperfusion (I/R) mouse model 781:832 Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. 37330081 7 34 theme intestinal 784:793 arg1 I/R 817:819 I/R 817:819 I/R 817:819 Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. 37330081 9 35 theme Omnibus 1164:1170 arg1 series 1172:1177 Gene Expression Omnibus series 1148:1177 Gene Expression Omnibus series 1148:1177 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 37330081 9 36 with Analysis 1134:1141 arg1 series 1172:1177 Gene Expression Omnibus series 1148:1177 Gene Expression Omnibus series 1148:1177 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 37330081 6 37 theme asymmetric 667:676 arg1 technique 700:708 asymmetric field-flow separation technique 667:708 asymmetric field-flow separation technique 667:708 By using asymmetric field-flow separation technique, GL-PPSQ2 were found to have a highly branched structure. 37330081 1 38 theme G. 247:248 arg1 lucidum 250:256 G. lucidum 247:256 G. lucidum 247:256 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 7 39 theme ischemia-reperfusion 795:814 arg1 model 828:832 an intestinal ischemia-reperfusion (I/R) mouse model 781:832 an intestinal ischemia-reperfusion (I/R) mouse model 781:832 Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. 37330081 3 40 theme anti-inflammatory 285:301 arg1 activities 338:347 anti-inflammatory, antioxidant, and immunoregulatory activities 285:347 anti-inflammatory, antioxidant, and immunoregulatory activities 285:347 Karst with anti-inflammatory, antioxidant, and immunoregulatory activities. 37330081 11 41 theme cytotoxic 1548:1556 arg1 NETs 1558:1561 cytotoxic NETs 1548:1561 cytotoxic NETs 1548:1561 GL-PPSQ2 could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. 37330081 7 42 theme mouse 822:826 arg1 model 828:832 an intestinal ischemia-reperfusion (I/R) mouse model 781:832 an intestinal ischemia-reperfusion (I/R) mouse model 781:832 Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. 37330081 11 43 theme oxidative 1492:1500 arg1 stress 1502:1507 oxidative stress 1492:1507 oxidative stress 1492:1507 GL-PPSQ2 could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. 37330081 4 44 contain have 431:434 arg2 proteins 458:465 48 proteins 455:465 48 proteins 455:465 We extracted and characterized a novel GLPP, named GL-PPSQ2, which were found to have 18 amino acids and 48 proteins, connected by O-glycosidic bonds. 37330081 4 44 contain have 431:434 arg1 GLPP 389:392 a novel GLPP 381:392 a novel GLPP 381:392 We extracted and characterized a novel GLPP, named GL-PPSQ2, which were found to have 18 amino acids and 48 proteins, connected by O-glycosidic bonds. 37330081 4 44 contain have 431:434 arg2 acids 445:449 18 amino acids 436:449 18 amino acids 436:449 We extracted and characterized a novel GLPP, named GL-PPSQ2, which were found to have 18 amino acids and 48 proteins, connected by O-glycosidic bonds. 37330081 9 45 theme Gene 1148:1151 arg1 series 1172:1177 Gene Expression Omnibus series 1148:1177 Gene Expression Omnibus series 1148:1177 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 37330081 1 46 dep ingredients 230:240 arg1 Leyss 259:263 Leyss 259:263 Leyss 259:263 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 1 47 from lucidum 250:256 arg1 ingredients 230:240 the main effective ingredients 211:240 the main effective ingredients from G. lucidum 211:256 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 1 47 from lucidum 250:256 arg1 peptides 191:198 Ganoderma lucidum polysaccharides peptides 157:198 Ganoderma lucidum polysaccharides peptides (GLPP) 157:205 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 10 48 theme NETs-related 1320:1331 arg1 MPO 1358:1360 MPO 1358:1360 MPO 1358:1360 GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. 37330081 10 48 theme NETs-related 1320:1331 arg1 myeloperoxidase 1341:1355 NETs-related protein myeloperoxidase 1320:1355 NETs-related protein myeloperoxidase (MPO) 1320:1361 GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. 37330081 0 49 theme ischemia-reperfusion 72:91 arg1 injury 93:98 intestinal ischemia-reperfusion injury 61:98 intestinal ischemia-reperfusion injury 61:98 Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps. 37330081 12 50 theme drug 1617:1620 arg1 candidate 1622:1630 a novel drug candidate 1609:1630 a novel drug candidate for preventing and treating intestinal I/R injury 1609:1680 This study proves that GL-PPSQ2 is a novel drug candidate for preventing and treating intestinal I/R injury. 37330081 12 50 theme drug 1617:1620 arg1 GL-PPSQ2 1597:1604 GL-PPSQ2 1597:1604 GL-PPSQ2 1597:1604 This study proves that GL-PPSQ2 is a novel drug candidate for preventing and treating intestinal I/R injury. 37330081 9 51 theme I/R 1278:1280 arg1 injury 1282:1287 intestinal I/R injury 1267:1287 intestinal I/R injury 1267:1287 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 37330081 9 52 theme Expression 1153:1162 arg1 series 1172:1177 Gene Expression Omnibus series 1148:1177 Gene Expression Omnibus series 1148:1177 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 37330081 1 53 theme Ganoderma 157:165 arg1 lucidum 167:173 Ganoderma lucidum 157:173 Ganoderma lucidum polysaccharides peptides (GLPP) 157:205 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 0 54 theme intestinal 61:70 arg1 injury 93:98 intestinal ischemia-reperfusion injury 61:98 intestinal ischemia-reperfusion injury 61:98 Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps. 37330081 11 55 theme cellular 1524:1531 arg1 apoptosis 1533:1541 cellular apoptosis 1524:1541 cellular apoptosis 1524:1541 GL-PPSQ2 could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. 37330081 4 56 theme amino 439:443 arg1 acids 445:449 18 amino acids 436:449 18 amino acids 436:449 We extracted and characterized a novel GLPP, named GL-PPSQ2, which were found to have 18 amino acids and 48 proteins, connected by O-glycosidic bonds. 37330081 6 57 theme branched 748:755 arg1 structure 757:765 a highly branched structure 739:765 a highly branched structure 739:765 By using asymmetric field-flow separation technique, GL-PPSQ2 were found to have a highly branched structure. 37330081 1 58 theme lucidum 167:173 arg1 GLPP 201:204 GLPP 201:204 GLPP 201:204 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 1 58 theme lucidum 167:173 arg1 peptides 191:198 Ganoderma lucidum polysaccharides peptides 157:198 Ganoderma lucidum polysaccharides peptides (GLPP) 157:205 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 1 58 theme lucidum 167:173 arg1 ingredients 230:240 the main effective ingredients 211:240 the main effective ingredients from G. lucidum 211:256 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 9 59 theme important 1249:1257 arg1 role 1259:1262 an important role 1246:1262 an important role 1246:1262 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 37330081 11 60 dep stress 1502:1507 arg1 formation 1563:1571 formation 1563:1571 formation 1563:1571 GL-PPSQ2 could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. 37330081 2 61 theme ex 266:267 arg1 Fr 269:270 ex Fr 266:270 ex Fr. 266:271 ex Fr.) 37330081 1 62 theme polysaccharides 175:189 arg1 GLPP 201:204 GLPP 201:204 GLPP 201:204 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 1 62 theme polysaccharides 175:189 arg1 peptides 191:198 Ganoderma lucidum polysaccharides peptides 157:198 Ganoderma lucidum polysaccharides peptides (GLPP) 157:205 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 1 62 theme polysaccharides 175:189 arg1 ingredients 230:240 the main effective ingredients 211:240 the main effective ingredients from G. lucidum 211:256 Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. 37330081 3 63 theme immunoregulatory 321:336 arg1 activities 338:347 anti-inflammatory, antioxidant, and immunoregulatory activities 285:347 anti-inflammatory, antioxidant, and immunoregulatory activities 285:347 Karst with anti-inflammatory, antioxidant, and immunoregulatory activities. 37330081 4 64 theme novel 383:387 arg1 GLPP 389:392 a novel GLPP 381:392 a novel GLPP 381:392 We extracted and characterized a novel GLPP, named GL-PPSQ2, which were found to have 18 amino acids and 48 proteins, connected by O-glycosidic bonds. 37330081 5 65 theme GL-PPSQ2 535:542 arg1 composition 520:530 The monosaccharide composition 501:530 The monosaccharide composition of GL-PPSQ2 501:542 The monosaccharide composition of GL-PPSQ2 was determined to be composed of fucose, mannose, galactose and glucose with a molar ratio of 1: 1.45:2.37:16.46. 37330081 7 66 theme intestinal 901:910 arg1 hemorrhage 920:929 intestinal mucosal hemorrhage 901:929 intestinal mucosal hemorrhage 901:929 Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. 37330081 3 67 with Karst 274:278 arg1 activities 338:347 anti-inflammatory, antioxidant, and immunoregulatory activities 285:347 anti-inflammatory, antioxidant, and immunoregulatory activities 285:347 Karst with anti-inflammatory, antioxidant, and immunoregulatory activities. 37330081 11 68 theme intestinal 1434:1443 arg1 I/R 1445:1447 intestinal I/R 1434:1447 intestinal I/R 1434:1447 GL-PPSQ2 could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. 37330081 7 69 theme mucosal 912:918 arg1 hemorrhage 920:929 intestinal mucosal hemorrhage 901:929 intestinal mucosal hemorrhage 901:929 Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. 37330081 12 70 theme novel 1611:1615 arg1 candidate 1622:1630 a novel drug candidate 1609:1630 a novel drug candidate for preventing and treating intestinal I/R injury 1609:1680 This study proves that GL-PPSQ2 is a novel drug candidate for preventing and treating intestinal I/R injury. 37330081 12 70 theme novel 1611:1615 arg1 GL-PPSQ2 1597:1604 GL-PPSQ2 1597:1604 GL-PPSQ2 1597:1604 This study proves that GL-PPSQ2 is a novel drug candidate for preventing and treating intestinal I/R injury. 37330081 6 71 contain have 734:737 arg2 structure 757:765 a highly branched structure 739:765 a highly branched structure 739:765 By using asymmetric field-flow separation technique, GL-PPSQ2 were found to have a highly branched structure. 37330081 6 71 contain have 734:737 arg1 GL-PPSQ2 711:718 GL-PPSQ2 711:718 GL-PPSQ2 711:718 By using asymmetric field-flow separation technique, GL-PPSQ2 were found to have a highly branched structure. 37330081 9 72 theme neutrophil 1194:1203 arg1 formation 1230:1238 neutrophil extracellular trap (NET) formation 1194:1238 neutrophil extracellular trap (NET) formation 1194:1238 Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. 34937426 12 0 theme transfected 1711:1721 arg1 cells 1723:1727 transfected cells 1711:1727 transfected cells cultured in absence or presence of tunicamycin 1711:1774 Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin indicated that SLC17A4 is subject to N-linked glycosylation. 34937426 5 1 theme studies 639:645 arg1 range 600:604 a broad range 592:604 a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4 592:695 We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. 34937426 6 2 theme different 800:808 arg1 metabolites 813:823 different TH metabolites 800:823 different TH metabolites 800:823 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 2 3 theme T4 347:348 arg1 transporter 350:360 T4 transporter 347:360 T4 transporter 347:360 Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. 34937426 2 3 theme T4 347:348 arg1 SLC17A4 229:235 Human SLC17A4 223:235 Human SLC17A4 223:235 Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. 34937426 13 4 theme extracellular 1927:1939 arg1 loop 1941:1944 extracellular loop 1 1927:1946 extracellular loop 1 1927:1946 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 7 5 from function 1060:1067 arg1 mutations 1023:1031 mutations 1023:1031 mutations in Asn residues on SLC17A4 function 1023:1067 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 10 6 theme classical 1489:1497 arg1 inhibitors 1514:1523 the classical TH transporter inhibitors 1485:1523 the classical TH transporter inhibitors studied 1485:1531 None of the classical TH transporter inhibitors studied attenuated SLC17A4-mediated TH transport. 34937426 11 7 theme T3 1614:1615 arg1 efflux 1604:1609 the efflux 1600:1609 the efflux of T3 and T4 1600:1622 SLC17A4 also facilitates the efflux of T3 and T4, and to a lesser extent of 3,3'-diiodothyronine (T2). 34937426 5 8 theme COS-1 650:654 arg1 cells 656:660 COS-1 cells 650:660 COS-1 cells transiently overexpressing SLC17A4 650:695 We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. 34937426 8 9 theme reverse 1139:1145 arg1 T3 1150:1151 reverse (r)T3 1139:1151 reverse (r)T3 1139:1151 SLC17A4 induced the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells. 34937426 6 10 theme SLC17A4-mediated 874:889 arg1 transport 894:902 SLC17A4-mediated TH transport 874:902 SLC17A4-mediated TH transport 874:902 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 1 11 theme thyroxine 192:200 arg1 concentrations 207:220 free thyroxine (T4) concentrations 187:220 free thyroxine (T4) concentrations 187:220 A recent genome-wide association study identified the SLC17A4 locus associated with circulating free thyroxine (T4) concentrations. 34937426 8 12 theme r 1148:1148 arg1 T3 1150:1151 reverse (r)T3 1139:1151 reverse (r)T3 1139:1151 SLC17A4 induced the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells. 34937426 6 13 theme transporters 858:869 arg1 metabolites 813:823 different TH metabolites 800:823 different TH metabolites 800:823 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 13 theme transporters 858:869 arg1 inhibitors 835:844 known inhibitors 829:844 known inhibitors of other TH transporters 829:869 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 5 14 theme TH 626:627 arg1 studies 639:645 well-established TH transport studies 609:645 well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4 609:695 We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. 34937426 2 15 theme novel 315:319 arg1 SLC17A4 229:235 Human SLC17A4 223:235 Human SLC17A4 223:235 Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. 34937426 2 15 theme novel 315:319 arg1 T3 339:340 T3 339:340 T3 339:340 Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. 34937426 2 15 theme novel 315:319 arg1 triiodothyronine 321:336 a novel triiodothyronine 313:336 a novel triiodothyronine (T3) 313:341 Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. 34937426 13 16 from located 1916:1922 arg1 loop 1941:1944 extracellular loop 1 1927:1946 extracellular loop 1 1927:1946 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 8 17 theme T3 1150:1151 arg1 uptake 1099:1104 the cellular uptake 1086:1104 the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells 1086:1183 SLC17A4 induced the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells. 34937426 10 18 theme transporter 1502:1512 arg1 inhibitors 1514:1523 the classical TH transporter inhibitors 1485:1523 the classical TH transporter inhibitors studied 1485:1531 None of the classical TH transporter inhibitors studied attenuated SLC17A4-mediated TH transport. 34937426 12 19 link N-linked 1813:1820 arg1 glycosylation 1822:1834 N-linked glycosylation 1813:1834 N-linked glycosylation 1813:1834 Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin indicated that SLC17A4 is subject to N-linked glycosylation. 34937426 9 20 theme iodine 1389:1394 arg1 moieties 1396:1403 at least three iodine moieties 1374:1403 at least three iodine moieties irrespective of the presence of modification at the alanine side chain 1374:1474 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 7 21 theme SLC17A4 1052:1058 arg1 function 1060:1067 SLC17A4 function 1052:1067 SLC17A4 function 1052:1067 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 9 22 theme irrespective 1405:1416 arg1 moieties 1396:1403 at least three iodine moieties 1374:1403 at least three iodine moieties irrespective of the presence of modification at the alanine side chain 1374:1474 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 10 23 theme SLC17A4-mediated 1544:1559 arg1 transport 1564:1572 SLC17A4-mediated TH transport 1544:1572 SLC17A4-mediated TH transport 1544:1572 None of the classical TH transporter inhibitors studied attenuated SLC17A4-mediated TH transport. 34937426 7 24 theme glycosylation 995:1007 arg1 tunicamycin 942:952 tunicamycin 942:952 tunicamycin 942:952 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 7 24 theme glycosylation 995:1007 arg1 inhibitor 973:981 a pharmacological inhibitor 955:981 a pharmacological inhibitor of N-linked glycosylation 955:1007 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 15 25 theme SLC17A4 2133:2139 arg1 role 2125:2128 the physiological role 2107:2128 the physiological role of SLC17A4 in TH regulation 2107:2156 Further studies should reveal the physiological role of SLC17A4 in TH regulation. 34937426 13 26 theme mutational 1851:1860 arg1 studies 1862:1868 Complementary mutational studies 1837:1868 Complementary mutational studies 1837:1868 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 9 27 theme T4 1200:1201 arg1 uptake 1190:1195 The uptake 1186:1195 The uptake of T4 by SLC17A4 1186:1212 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 1 28 theme SLC17A4 145:151 arg1 locus 153:157 the SLC17A4 locus 141:157 the SLC17A4 locus associated with circulating free thyroxine (T4) concentrations 141:220 A recent genome-wide association study identified the SLC17A4 locus associated with circulating free thyroxine (T4) concentrations. 34937426 15 29 theme physiological 2111:2123 arg1 role 2125:2128 the physiological role 2107:2128 the physiological role of SLC17A4 in TH regulation 2107:2156 Further studies should reveal the physiological role of SLC17A4 in TH regulation. 34937426 11 30 theme 3,3'-diiodothyronine 1651:1670 arg1 extent 1641:1646 a lesser extent 1632:1646 a lesser extent of 3,3'-diiodothyronine (T2) 1632:1675 SLC17A4 also facilitates the efflux of T3 and T4, and to a lesser extent of 3,3'-diiodothyronine (T2). 34937426 0 31 theme Hormone 62:68 arg1 SLC17A4 82:88 the Novel and Specific Thyroid Hormone Transporter SLC17A4 31:88 the Novel and Specific Thyroid Hormone Transporter SLC17A4 31:88 Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4. 34937426 7 32 theme pharmacological 957:971 arg1 tunicamycin 942:952 tunicamycin 942:952 tunicamycin 942:952 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 7 32 theme pharmacological 957:971 arg1 inhibitor 973:981 a pharmacological inhibitor 955:981 a pharmacological inhibitor of N-linked glycosylation 955:1007 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 5 33 from range 600:604 arg1 cells 656:660 COS-1 cells 650:660 COS-1 cells transiently overexpressing SLC17A4 650:695 We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. 34937426 0 34 theme SLC17A4 82:88 arg1 Characterization 11:26 Functional Characterization 0:26 Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4. 0:89 Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4. 34937426 9 35 theme alanine 1457:1463 arg1 chain 1470:1474 the alanine side chain 1453:1474 the alanine side chain 1453:1474 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 9 36 contain contain 1366:1372 arg2 moieties 1396:1403 at least three iodine moieties 1374:1403 at least three iodine moieties irrespective of the presence of modification at the alanine side chain 1374:1474 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 9 36 contain contain 1366:1372 arg1 iodothyronines 1302:1315 various iodothyronines 1294:1315 various iodothyronines 1294:1315 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 9 36 contain contain 1366:1372 arg1 those 1355:1359 those 1355:1359 those 1355:1359 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 13 37 theme primary 1952:1958 arg1 Asn75 1888:1892 Asn75 1888:1892 Asn75 1888:1892 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 13 37 theme primary 1952:1958 arg1 Asn90 1899:1903 Asn90 1899:1903 Asn90 1899:1903 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 13 37 theme primary 1952:1958 arg1 Asn66 1881:1885 Asn66 1881:1885 Asn66 1881:1885 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 13 37 theme primary 1952:1958 arg1 targets 1960:1966 primary targets 1952:1966 primary targets 1952:1966 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 12 38 from studies 1689:1695 arg1 lysates 1700:1706 lysates 1700:1706 lysates of transfected cells cultured in absence or presence of tunicamycin 1700:1774 Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin indicated that SLC17A4 is subject to N-linked glycosylation. 34937426 15 39 from role 2125:2128 arg1 regulation 2147:2156 TH regulation 2144:2156 TH regulation 2144:2156 Further studies should reveal the physiological role of SLC17A4 in TH regulation. 34937426 0 40 theme Functional 0:9 arg1 Characterization 11:26 Functional Characterization 0:26 Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4. 0:89 Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4. 34937426 1 41 theme recent 93:98 arg1 study 124:128 A recent genome-wide association study 91:128 A recent genome-wide association study 91:128 A recent genome-wide association study identified the SLC17A4 locus associated with circulating free thyroxine (T4) concentrations. 34937426 4 42 theme novel 539:543 arg1 TH 562:563 TH 562:563 TH 562:563 In this study, we delineated basic transporter characteristics of this novel thyroid hormone (TH) transporter. 34937426 4 42 theme novel 539:543 arg1 hormone 553:559 novel thyroid hormone 539:559 this novel thyroid hormone (TH) transporter 534:576 In this study, we delineated basic transporter characteristics of this novel thyroid hormone (TH) transporter. 34937426 9 43 theme extracellular 1261:1273 arg1 pH 1275:1276 low extracellular pH 1257:1276 low extracellular pH 1257:1276 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 6 44 theme TH 855:856 arg1 transporters 858:869 other TH transporters 849:869 other TH transporters 849:869 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 1 45 theme association 112:122 arg1 study 124:128 A recent genome-wide association study 91:128 A recent genome-wide association study 91:128 A recent genome-wide association study identified the SLC17A4 locus associated with circulating free thyroxine (T4) concentrations. 34937426 6 46 from efflux 762:767 arg1 buffers 750:756 various incubation buffers 731:756 various incubation buffers 731:756 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 46 from efflux 762:767 arg1 transport 894:902 SLC17A4-mediated TH transport 874:902 SLC17A4-mediated TH transport 874:902 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 4 47 theme hormone 553:559 arg1 transporter 566:576 this novel thyroid hormone (TH) transporter 534:576 this novel thyroid hormone (TH) transporter 534:576 In this study, we delineated basic transporter characteristics of this novel thyroid hormone (TH) transporter. 34937426 0 48 theme Novel 35:39 arg1 SLC17A4 82:88 the Novel and Specific Thyroid Hormone Transporter SLC17A4 31:88 the Novel and Specific Thyroid Hormone Transporter SLC17A4 31:88 Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4. 34937426 3 49 theme cellular 387:394 arg1 uptake 396:401 the cellular uptake 383:401 the cellular uptake of T3 and T4 383:414 However, apart from the cellular uptake of T3 and T4, transporter characteristics are currently unknown. 34937426 4 50 theme transporter 503:513 arg1 characteristics 515:529 basic transporter characteristics 497:529 basic transporter characteristics of this novel thyroid hormone (TH) transporter 497:576 In this study, we delineated basic transporter characteristics of this novel thyroid hormone (TH) transporter. 34937426 0 51 theme Specific 45:52 arg1 SLC17A4 82:88 the Novel and Specific Thyroid Hormone Transporter SLC17A4 31:88 the Novel and Specific Thyroid Hormone Transporter SLC17A4 31:88 Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4. 34937426 6 52 theme known 829:833 arg1 inhibitors 835:844 known inhibitors 829:844 known inhibitors of other TH transporters 829:869 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 53 theme incubation 739:748 arg1 buffers 750:756 various incubation buffers 731:756 various incubation buffers 731:756 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 9 54 theme various 1294:1300 arg1 iodothyronines 1302:1315 various iodothyronines 1294:1315 various iodothyronines 1294:1315 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 9 54 theme various 1294:1300 arg1 those 1355:1359 those 1355:1359 those 1355:1359 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 8 55 theme T3 1109:1110 arg1 uptake 1099:1104 the cellular uptake 1086:1104 the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells 1086:1183 SLC17A4 induced the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells. 34937426 6 56 theme metabolites 813:823 arg1 effects 789:795 the inhibitory effects 774:795 the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport 774:902 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 56 theme metabolites 813:823 arg1 efflux 762:767 TH efflux 759:767 TH efflux 759:767 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 56 theme metabolites 813:823 arg1 uptake 721:726 cellular TH uptake 709:726 cellular TH uptake in various incubation buffers 709:756 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 11 57 theme lesser 1634:1639 arg1 extent 1641:1646 a lesser extent 1632:1646 a lesser extent of 3,3'-diiodothyronine (T2) 1632:1675 SLC17A4 also facilitates the efflux of T3 and T4, and to a lesser extent of 3,3'-diiodothyronine (T2). 34937426 15 58 theme Further 2077:2083 arg1 studies 2085:2091 Further studies 2077:2091 Further studies 2077:2091 Further studies should reveal the physiological role of SLC17A4 in TH regulation. 34937426 5 59 from cells 656:660 arg1 range 600:604 a broad range 592:604 a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4 592:695 We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. 34937426 8 60 theme T4 1116:1117 arg1 uptake 1099:1104 the cellular uptake 1086:1104 the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells 1086:1183 SLC17A4 induced the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells. 34937426 12 61 theme cells 1723:1727 arg1 lysates 1700:1706 lysates 1700:1706 lysates of transfected cells cultured in absence or presence of tunicamycin 1700:1774 Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin indicated that SLC17A4 is subject to N-linked glycosylation. 34937426 7 62 from residues 1040:1047 arg1 function 1060:1067 SLC17A4 function 1052:1067 SLC17A4 function 1052:1067 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 5 63 theme transport 629:637 arg1 studies 639:645 well-established TH transport studies 609:645 well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4 609:695 We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. 34937426 6 64 theme TH 718:719 arg1 uptake 721:726 cellular TH uptake 709:726 cellular TH uptake in various incubation buffers 709:756 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 8 65 theme ∼4 1122:1123 arg1 times 1125:1129 ∼4 times 1122:1129 ∼4 times 1122:1129 SLC17A4 induced the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells. 34937426 12 66 theme Immunoblot 1678:1687 arg1 studies 1689:1695 Immunoblot studies 1678:1695 Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin 1678:1774 Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin indicated that SLC17A4 is subject to N-linked glycosylation. 34937426 10 67 theme TH 1499:1500 arg1 inhibitors 1514:1523 the classical TH transporter inhibitors 1485:1523 the classical TH transporter inhibitors studied 1485:1531 None of the classical TH transporter inhibitors studied attenuated SLC17A4-mediated TH transport. 34937426 6 68 theme TH 891:892 arg1 transport 894:902 SLC17A4-mediated TH transport 874:902 SLC17A4-mediated TH transport 874:902 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 4 69 theme transporter 566:576 arg1 characteristics 515:529 basic transporter characteristics 497:529 basic transporter characteristics of this novel thyroid hormone (TH) transporter 497:576 In this study, we delineated basic transporter characteristics of this novel thyroid hormone (TH) transporter. 34937426 6 70 theme inhibitory 778:787 arg1 effects 789:795 the inhibitory effects 774:795 the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport 774:902 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 1 71 theme free 187:190 arg1 T4 203:204 T4 203:204 T4 203:204 A recent genome-wide association study identified the SLC17A4 locus associated with circulating free thyroxine (T4) concentrations. 34937426 1 71 theme free 187:190 arg1 thyroxine 192:200 free thyroxine 187:200 free thyroxine (T4) concentrations 187:220 A recent genome-wide association study identified the SLC17A4 locus associated with circulating free thyroxine (T4) concentrations. 34937426 9 72 from presence 1425:1432 arg1 chain 1470:1474 the alanine side chain 1453:1474 the alanine side chain 1453:1474 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 8 73 theme control 1171:1177 arg1 cells 1179:1183 control cells 1171:1183 control cells 1171:1183 SLC17A4 induced the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells. 34937426 5 74 theme well-established 609:624 arg1 studies 639:645 well-established TH transport studies 609:645 well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4 609:695 We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. 34937426 10 75 theme inhibitors 1514:1523 arg1 None 1477:1480 None 1477:1480 None of the classical TH transporter inhibitors studied 1477:1531 None of the classical TH transporter inhibitors studied attenuated SLC17A4-mediated TH transport. 34937426 7 76 link N-linked 986:993 arg1 glycosylation 995:1007 N-linked glycosylation 986:1007 N-linked glycosylation 986:1007 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 13 77 from loop 1941:1944 arg1 located 1916:1922 located 1916:1922 located 1916:1922 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 13 78 located located 1916:1922 arg2 Asn66 1881:1885 Asn66 1881:1885 Asn66 1881:1885 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 13 78 located located 1916:1922 arg2 Asn90 1899:1903 Asn90 1899:1903 Asn90 1899:1903 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 13 78 located located 1916:1922 arg2 targets 1960:1966 primary targets 1952:1966 primary targets 1952:1966 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 13 78 located located 1916:1922 arg1 loop 1941:1944 extracellular loop 1 1927:1946 extracellular loop 1 1927:1946 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 13 78 located located 1916:1922 arg2 Asn75 1888:1892 Asn75 1888:1892 Asn75 1888:1892 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 15 79 theme TH 2144:2145 arg1 regulation 2147:2156 TH regulation 2144:2156 TH regulation 2144:2156 Further studies should reveal the physiological role of SLC17A4 in TH regulation. 34937426 10 80 theme TH 1561:1562 arg1 transport 1564:1572 SLC17A4-mediated TH transport 1544:1572 SLC17A4-mediated TH transport 1544:1572 None of the classical TH transporter inhibitors studied attenuated SLC17A4-mediated TH transport. 34937426 7 81 theme Asn 1036:1038 arg1 residues 1040:1047 Asn residues 1036:1047 Asn residues on SLC17A4 function 1036:1067 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 13 82 theme Complementary 1837:1849 arg1 studies 1862:1868 Complementary mutational studies 1837:1868 Complementary mutational studies 1837:1868 Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. 34937426 2 83 theme gastrointestinal 268:283 arg1 tract 285:289 the gastrointestinal tract 264:289 the gastrointestinal tract 264:289 Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. 34937426 9 84 theme presence 1425:1432 arg1 irrespective 1405:1416 irrespective 1405:1416 irrespective 1405:1416 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 0 85 theme Transporter 70:80 arg1 SLC17A4 82:88 the Novel and Specific Thyroid Hormone Transporter SLC17A4 31:88 the Novel and Specific Thyroid Hormone Transporter SLC17A4 31:88 Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4. 34937426 7 86 theme N-linked 986:993 arg1 glycosylation 995:1007 N-linked glycosylation 986:1007 N-linked glycosylation 986:1007 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 9 87 theme modification 1437:1448 arg1 presence 1425:1432 the presence 1421:1432 the presence of modification at the alanine side chain 1421:1474 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 12 88 theme tunicamycin 1764:1774 arg1 presence 1752:1759 presence 1752:1759 presence 1752:1759 Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin indicated that SLC17A4 is subject to N-linked glycosylation. 34937426 12 88 theme tunicamycin 1764:1774 arg1 absence 1741:1747 absence 1741:1747 absence 1741:1747 Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin indicated that SLC17A4 is subject to N-linked glycosylation. 34937426 4 89 theme basic 497:501 arg1 characteristics 515:529 basic transporter characteristics 497:529 basic transporter characteristics of this novel thyroid hormone (TH) transporter 497:576 In this study, we delineated basic transporter characteristics of this novel thyroid hormone (TH) transporter. 34937426 14 90 theme T4 2035:2036 arg1 transport 2015:2023 the transport 2011:2023 the transport of T3 and T4 2011:2036 Our studies show that SLC17A4 facilitates the transport of T3 and T4, and less efficiently rT3 and 3,3'-T2. 34937426 9 91 theme side 1465:1468 arg1 chain 1470:1474 the alanine side chain 1453:1474 the alanine side chain 1453:1474 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 9 92 from chain 1470:1474 arg1 presence 1425:1432 the presence 1421:1432 the presence of modification at the alanine side chain 1421:1474 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 9 92 from chain 1470:1474 arg1 modification 1437:1448 modification 1437:1448 modification at the alanine side chain 1437:1474 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 14 93 theme T3 2028:2029 arg1 transport 2015:2023 the transport 2011:2023 the transport of T3 and T4 2011:2036 Our studies show that SLC17A4 facilitates the transport of T3 and T4, and less efficiently rT3 and 3,3'-T2. 34937426 6 94 theme cellular 709:716 arg1 uptake 721:726 cellular TH uptake 709:726 cellular TH uptake in various incubation buffers 709:756 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 12 95 theme N-linked 1813:1820 arg1 glycosylation 1822:1834 N-linked glycosylation 1813:1834 N-linked glycosylation 1813:1834 Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin indicated that SLC17A4 is subject to N-linked glycosylation. 34937426 5 96 theme broad 594:598 arg1 range 600:604 a broad range 592:604 a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4 592:695 We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. 34937426 6 97 from effects 789:795 arg1 buffers 750:756 various incubation buffers 731:756 various incubation buffers 731:756 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 97 from effects 789:795 arg1 transport 894:902 SLC17A4-mediated TH transport 874:902 SLC17A4-mediated TH transport 874:902 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 3 98 theme transporter 417:427 arg1 characteristics 429:443 transporter characteristics 417:443 transporter characteristics 417:443 However, apart from the cellular uptake of T3 and T4, transporter characteristics are currently unknown. 34937426 4 99 theme thyroid 545:551 arg1 TH 562:563 TH 562:563 TH 562:563 In this study, we delineated basic transporter characteristics of this novel thyroid hormone (TH) transporter. 34937426 4 99 theme thyroid 545:551 arg1 hormone 553:559 novel thyroid hormone 539:559 this novel thyroid hormone (TH) transporter 534:576 In this study, we delineated basic transporter characteristics of this novel thyroid hormone (TH) transporter. 34937426 3 100 theme T4 413:414 arg1 uptake 396:401 the cellular uptake 383:401 the cellular uptake of T3 and T4 383:414 However, apart from the cellular uptake of T3 and T4, transporter characteristics are currently unknown. 34937426 9 101 theme low 1257:1259 arg1 pH 1275:1276 low extracellular pH 1257:1276 low extracellular pH 1257:1276 The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. 34937426 7 102 theme tunicamycin 942:952 arg1 effect 932:937 the effect 928:937 the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, 928:1008 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 1 103 theme genome-wide 100:110 arg1 study 124:128 A recent genome-wide association study 91:128 A recent genome-wide association study 91:128 A recent genome-wide association study identified the SLC17A4 locus associated with circulating free thyroxine (T4) concentrations. 34937426 8 104 theme cellular 1090:1097 arg1 uptake 1099:1104 the cellular uptake 1086:1104 the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells 1086:1183 SLC17A4 induced the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells. 34937426 6 105 theme other 849:853 arg1 transporters 858:869 other TH transporters 849:869 other TH transporters 849:869 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 3 106 theme T3 406:407 arg1 uptake 396:401 the cellular uptake 383:401 the cellular uptake of T3 and T4 383:414 However, apart from the cellular uptake of T3 and T4, transporter characteristics are currently unknown. 34937426 11 107 theme T4 1621:1622 arg1 efflux 1604:1609 the efflux 1600:1609 the efflux of T3 and T4 1600:1622 SLC17A4 also facilitates the efflux of T3 and T4, and to a lesser extent of 3,3'-diiodothyronine (T2). 34937426 6 108 theme TH 759:760 arg1 efflux 762:767 TH efflux 759:767 TH efflux 759:767 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 0 109 theme Thyroid 54:60 arg1 SLC17A4 82:88 the Novel and Specific Thyroid Hormone Transporter SLC17A4 31:88 the Novel and Specific Thyroid Hormone Transporter SLC17A4 31:88 Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4. 34937426 6 110 theme inhibitors 835:844 arg1 effects 789:795 the inhibitory effects 774:795 the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport 774:902 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 110 theme inhibitors 835:844 arg1 efflux 762:767 TH efflux 759:767 TH efflux 759:767 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 110 theme inhibitors 835:844 arg1 uptake 721:726 cellular TH uptake 709:726 cellular TH uptake in various incubation buffers 709:756 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 2 111 theme Human 223:227 arg1 transporter 350:360 T4 transporter 347:360 T4 transporter 347:360 Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. 34937426 2 111 theme Human 223:227 arg1 SLC17A4 229:235 Human SLC17A4 223:235 Human SLC17A4 223:235 Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. 34937426 2 111 theme Human 223:227 arg1 triiodothyronine 321:336 a novel triiodothyronine 313:336 a novel triiodothyronine (T3) 313:341 Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. 34937426 5 112 from studies 639:645 arg1 cells 656:660 COS-1 cells 650:660 COS-1 cells transiently overexpressing SLC17A4 650:695 We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. 34937426 7 113 from mutations 1023:1031 arg1 residues 1040:1047 Asn residues 1036:1047 Asn residues on SLC17A4 function 1036:1067 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 7 113 from mutations 1023:1031 arg1 function 1060:1067 SLC17A4 function 1052:1067 SLC17A4 function 1052:1067 Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. 34937426 6 114 theme various 731:737 arg1 buffers 750:756 various incubation buffers 731:756 various incubation buffers 731:756 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 115 theme TH 810:811 arg1 metabolites 813:823 different TH metabolites 800:823 different TH metabolites 800:823 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 116 from uptake 721:726 arg1 buffers 750:756 various incubation buffers 731:756 various incubation buffers 731:756 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 34937426 6 116 from uptake 721:726 arg1 transport 894:902 SLC17A4-mediated TH transport 874:902 SLC17A4-mediated TH transport 874:902 We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. 35507766 2 0 theme stem 514:517 arg1 cells 519:523 human-induced pluripotent stem cells 488:523 human-induced pluripotent stem cells (iPSCs) 488:531 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 2 0 theme stem 514:517 arg1 iPSCs 526:530 iPSCs 526:530 iPSCs 526:530 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 9 1 theme unknown 1775:1781 arg1 roles 1797:1801 heretofore unknown physiological roles 1764:1801 heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis 1764:1892 Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis. 35507766 5 2 theme double-knockout 1121:1135 arg1 iPSCs 1137:1141 double-knockout iPSCs 1121:1141 double-knockout iPSCs 1121:1141 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 9 3 theme physiological 1783:1795 arg1 roles 1797:1801 heretofore unknown physiological roles 1764:1801 heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis 1764:1892 Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis. 35507766 5 4 theme cellular 1282:1289 arg1 sialyltransferases 1300:1317 functional cellular O-glycan sialyltransferases 1271:1317 functional cellular O-glycan sialyltransferases 1271:1317 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 5 4 theme cellular 1282:1289 arg1 both 1253:1256 both 1253:1256 both 1253:1256 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 1 5 theme Galβ1,3GalNAc 259:271 arg1 in vitro 274:281 type III disaccharides (Galβ1,3GalNAc) in vitro 235:281 type III disaccharides (Galβ1,3GalNAc) in vitro 235:281 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 0 6 theme hematopoietic 71:83 arg1 differentiation 104:118 hematopoietic and megakaryocytic differentiation 71:118 differentiation 104:118 Overlapping and unique substrate specificities of ST3GAL1 and 2 during hematopoietic and megakaryocytic differentiation. 35507766 9 7 from sialylation 1846:1856 arg1 megakaryocytopoiesis 1873:1892 megakaryocytopoiesis 1873:1892 megakaryocytopoiesis 1873:1892 Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis. 35507766 9 7 from sialylation 1846:1856 arg1 hemato- 1861:1867 hemato- 1861:1867 hemato- 1861:1867 Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis. 35507766 5 8 theme O-glycan 1291:1298 arg1 sialyltransferases 1300:1317 functional cellular O-glycan sialyltransferases 1271:1317 functional cellular O-glycan sialyltransferases 1271:1317 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 5 8 theme O-glycan 1291:1298 arg1 both 1253:1256 both 1253:1256 both 1253:1256 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 2 9 theme hematopoietic 538:550 arg1 HPCs 570:573 HPCs 570:573 HPCs 570:573 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 2 9 theme hematopoietic 538:550 arg1 cells 563:567 hematopoietic progenitor cells 538:567 hematopoietic progenitor cells (HPCs) 538:574 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 5 10 dep one 1201:1203 arg1 either 1194:1199 either 1194:1199 either 1194:1199 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 8 11 theme little 1621:1626 arg1 impact 1628:1633 little impact 1621:1633 little impact 1621:1633 Finally, although disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. 35507766 5 12 theme peanut 971:976 arg1 lectin 989:994 the peanut agglutinin lectin 967:994 the peanut agglutinin lectin 967:994 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 8 13 theme impaired 1692:1699 arg1 formation 1716:1724 dramatically impaired MK proplatelet formation 1679:1724 dramatically impaired MK proplatelet formation 1679:1724 Finally, although disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. 35507766 1 14 theme in vitro 274:281 arg1 in vitro 274:281 type III disaccharides (Galβ1,3GalNAc) in vitro 235:281 type III disaccharides (Galβ1,3GalNAc) in vitro 235:281 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 1 14 theme in vitro 274:281 arg1 residue 224:230 the galactose residue 210:230 the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro 210:281 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 0 15 theme megakaryocytic 89:102 arg1 differentiation 104:118 hematopoietic and megakaryocytic differentiation 71:118 differentiation 104:118 Overlapping and unique substrate specificities of ST3GAL1 and 2 during hematopoietic and megakaryocytic differentiation. 35507766 5 16 theme agglutinin 978:987 arg1 lectin 989:994 the peanut agglutinin lectin 967:994 the peanut agglutinin lectin 967:994 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 8 17 theme MK 1638:1639 arg1 production 1641:1650 MK production 1638:1650 MK production 1638:1650 Finally, although disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. 35507766 6 18 theme MK 1377:1378 arg1 GP 1403:1404 GP 1403:1404 GP 1403:1404 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 18 theme MK 1377:1378 arg1 glycoprotein 1389:1400 MK membrane glycoprotein 1377:1400 MK membrane glycoprotein (GP) GPIbα 1377:1411 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 19 theme GP 1439:1440 arg1 substrates 1442:1451 major GP substrates 1433:1451 major GP substrates for ST3GAL1 and ST3GAL2 1433:1475 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 19 theme GP 1439:1440 arg1 markers 1343:1349 the HPC markers CD34 and CD43 1335:1363 the HPC markers CD34 and CD43 1335:1363 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 19 theme GP 1439:1440 arg1 GPIbα 1407:1411 MK membrane glycoprotein (GP) GPIbα 1377:1411 MK membrane glycoprotein (GP) GPIbα 1377:1411 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 5 20 theme lectin 989:994 arg1 Binding 956:962 Binding 956:962 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, 956:1067 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 8 21 theme proplatelet 1704:1714 arg1 formation 1716:1724 dramatically impaired MK proplatelet formation 1679:1724 dramatically impaired MK proplatelet formation 1679:1724 Finally, although disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. 35507766 5 22 theme sialyltransferases 1214:1231 arg1 one 1201:1203 one 1201:1203 one 1201:1203 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 5 22 theme sialyltransferases 1214:1231 arg1 sialyltransferases 1214:1231 these sialyltransferases 1208:1231 these sialyltransferases 1208:1231 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 8 23 contain had 1617:1619 arg1 disruption 1583:1592 disruption 1583:1592 disruption of ST3GAL1 and ST3GAL2 1583:1615 Finally, although disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. 35507766 8 23 contain had 1617:1619 arg2 impact 1628:1633 little impact 1621:1633 little impact 1621:1633 Finally, although disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. 35507766 1 24 dep sialyltransferases 134:151 arg1 ST3GAL1 153:159 ST3GAL1 153:159 ST3GAL1 153:159 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 1 24 dep sialyltransferases 134:151 arg1 sialyltransferases 134:151 the sialyltransferases ST3GAL1 and ST3GAL2 130:171 the sialyltransferases ST3GAL1 and ST3GAL2 130:171 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 1 24 dep sialyltransferases 134:151 arg1 ST3GAL2 165:171 ST3GAL2 165:171 ST3GAL2 165:171 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 1 25 theme sialic 195:200 arg1 acid 202:205 sialic acid 195:205 sialic acid 195:205 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 5 26 gly unsialylated 1027:1038 arg1 chains 1061:1066 unsialylated Galβ1,3GalNAc glycan chains 1027:1066 unsialylated Galβ1,3GalNAc glycan chains 1027:1066 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 2 27 theme pluripotent 502:512 arg1 cells 519:523 human-induced pluripotent stem cells 488:523 human-induced pluripotent stem cells (iPSCs) 488:531 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 2 27 theme pluripotent 502:512 arg1 iPSCs 526:530 iPSCs 526:530 iPSCs 526:530 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 1 28 from sialylation 284:294 arg1 cells 340:344 living cells 333:344 living cells 333:344 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 9 29 gly sialylation 1846:1856 arg1 megakaryocytopoiesis 1873:1892 megakaryocytopoiesis 1873:1892 megakaryocytopoiesis 1873:1892 Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis. 35507766 9 29 gly sialylation 1846:1856 arg1 hemato- 1861:1867 hemato- 1861:1867 hemato- 1861:1867 Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis. 35507766 9 30 theme glycan 1839:1844 arg1 sialylation 1846:1856 O-linked glycan sialylation 1830:1856 O-linked glycan sialylation in hemato- and megakaryocytopoiesis 1830:1892 Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis. 35507766 7 31 theme GPIIb 1508:1512 arg1 O-sialylation 1491:1503 O-sialylation 1491:1503 O-sialylation of GPIIb 1491:1512 In contrast, O-sialylation of GPIIb relied predominantly on the expression of ST3GAL2. 35507766 5 32 theme chains 1061:1066 arg1 presence 1015:1022 the presence 1011:1022 the presence of unsialylated Galβ1,3GalNAc glycan chains 1011:1066 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 7 33 gly O-sialylation 1491:1503 arg1 GPIIb 1508:1512 GPIIb 1508:1512 GPIIb 1508:1512 In contrast, O-sialylation of GPIIb relied predominantly on the expression of ST3GAL2. 35507766 0 34 theme substrate 23:31 arg1 specificities 33:45 unique substrate specificities 16:45 unique substrate specificities of ST3GAL1 16:56 Overlapping and unique substrate specificities of ST3GAL1 and 2 during hematopoietic and megakaryocytic differentiation. 35507766 4 35 theme human 938:942 arg1 lines 949:953 doubly deficient human iPSC lines 921:953 doubly deficient human iPSC lines 921:953 To further delineate their role in these processes, we generated ST3GAL1-, ST3GAL2-, and doubly deficient human iPSC lines. 35507766 7 36 theme ST3GAL2 1556:1562 arg1 expression 1542:1551 the expression 1538:1551 the expression of ST3GAL2 1538:1562 In contrast, O-sialylation of GPIIb relied predominantly on the expression of ST3GAL2. 35507766 9 37 theme O-linked 1830:1837 arg1 sialylation 1846:1856 O-linked glycan sialylation 1830:1856 O-linked glycan sialylation in hemato- and megakaryocytopoiesis 1830:1892 Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis. 35507766 0 38 theme unique 16:21 arg1 specificities 33:45 unique substrate specificities 16:45 unique substrate specificities of ST3GAL1 16:56 Overlapping and unique substrate specificities of ST3GAL1 and 2 during hematopoietic and megakaryocytic differentiation. 35507766 1 39 theme O-linked 299:306 arg1 proteins 321:328 O-linked glycosylated proteins 299:328 O-linked glycosylated proteins 299:328 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 4 40 theme deficient 928:936 arg1 lines 949:953 doubly deficient human iPSC lines 921:953 doubly deficient human iPSC lines 921:953 To further delineate their role in these processes, we generated ST3GAL1-, ST3GAL2-, and doubly deficient human iPSC lines. 35507766 4 41 theme iPSC 944:947 arg1 lines 949:953 doubly deficient human iPSC lines 921:953 doubly deficient human iPSC lines 921:953 To further delineate their role in these processes, we generated ST3GAL1-, ST3GAL2-, and doubly deficient human iPSC lines. 35507766 1 42 theme galactose 214:222 arg1 in vitro 274:281 type III disaccharides (Galβ1,3GalNAc) in vitro 235:281 type III disaccharides (Galβ1,3GalNAc) in vitro 235:281 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 1 42 theme galactose 214:222 arg1 residue 224:230 the galactose residue 210:230 the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro 210:281 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 2 43 theme human-induced 488:500 arg1 cells 519:523 human-induced pluripotent stem cells 488:523 human-induced pluripotent stem cells (iPSCs) 488:531 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 2 43 theme human-induced 488:500 arg1 iPSCs 526:530 iPSCs 526:530 iPSCs 526:530 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 1 44 theme glycosylated 308:319 arg1 proteins 321:328 O-linked glycosylated proteins 299:328 O-linked glycosylated proteins 299:328 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 8 45 theme MK 1701:1702 arg1 formation 1716:1724 dramatically impaired MK proplatelet formation 1679:1724 dramatically impaired MK proplatelet formation 1679:1724 Finally, although disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. 35507766 8 46 theme ST3GAL1 1597:1603 arg1 disruption 1583:1592 disruption 1583:1592 disruption of ST3GAL1 and ST3GAL2 1583:1615 Finally, although disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. 35507766 1 47 theme proteins 321:328 arg1 sialylation 284:294 sialylation 284:294 sialylation of O-linked glycosylated proteins in living cells 284:344 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 2 48 theme progenitor 552:561 arg1 HPCs 570:573 HPCs 570:573 HPCs 570:573 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 2 48 theme progenitor 552:561 arg1 cells 563:567 hematopoietic progenitor cells 538:567 hematopoietic progenitor cells (HPCs) 538:574 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 9 49 from roles 1797:1801 arg1 sialylation 1846:1856 O-linked glycan sialylation 1830:1856 O-linked glycan sialylation in hemato- and megakaryocytopoiesis 1830:1892 Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis. 35507766 5 50 theme unsialylated 1027:1038 arg1 chains 1061:1066 unsialylated Galβ1,3GalNAc glycan chains 1027:1066 unsialylated Galβ1,3GalNAc glycan chains 1027:1066 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 4 51 from role 859:862 arg1 processes 873:881 these processes 867:881 these processes 867:881 To further delineate their role in these processes, we generated ST3GAL1-, ST3GAL2-, and doubly deficient human iPSC lines. 35507766 2 52 theme ST3GAL2 409:415 arg1 role 401:404 the role 397:404 the role of ST3GAL2 in O-sialylation 397:432 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 3 53 theme expression 796:805 arg1 coordination 780:791 coordination 780:791 coordination of expression during megakaryopoiesis 780:829 ST3GAL1 and ST3GAL2 each became highly expressed during the differentiation of iPSCs to HPCs but decreased markedly in their expression upon differentiation into MKs, suggesting coordination of expression during megakaryopoiesis. 35507766 6 54 theme glycoprotein 1389:1400 arg1 substrates 1442:1451 major GP substrates 1433:1451 major GP substrates for ST3GAL1 and ST3GAL2 1433:1475 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 54 theme glycoprotein 1389:1400 arg1 markers 1343:1349 the HPC markers CD34 and CD43 1335:1363 the HPC markers CD34 and CD43 1335:1363 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 54 theme glycoprotein 1389:1400 arg1 GPIbα 1407:1411 MK membrane glycoprotein (GP) GPIbα 1377:1411 MK membrane glycoprotein (GP) GPIbα 1377:1411 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 5 55 theme Galβ1,3GalNAc 1040:1052 arg1 chains 1061:1066 unsialylated Galβ1,3GalNAc glycan chains 1027:1066 unsialylated Galβ1,3GalNAc glycan chains 1027:1066 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 1 56 gly sialylation 284:294 arg1 proteins 321:328 O-linked glycosylated proteins 299:328 O-linked glycosylated proteins 299:328 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 1 56 gly sialylation 284:294 arg1 cells 340:344 living cells 333:344 living cells 333:344 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 6 57 gly glycoprotein 1389:1400 arg1 GP 1403:1404 GP 1403:1404 GP 1403:1404 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 57 gly glycoprotein 1389:1400 arg1 glycoprotein 1389:1400 MK membrane glycoprotein 1377:1400 MK membrane glycoprotein (GP) GPIbα 1377:1411 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 0 58 theme ST3GAL1 50:56 arg1 specificities 33:45 unique substrate specificities 16:45 unique substrate specificities of ST3GAL1 16:56 Overlapping and unique substrate specificities of ST3GAL1 and 2 during hematopoietic and megakaryocytic differentiation. 35507766 1 59 theme living 333:338 arg1 cells 340:344 living cells 333:344 living cells 333:344 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 3 60 theme iPSCs 681:685 arg1 differentiation 662:676 the differentiation 658:676 the differentiation of iPSCs to HPCs 658:693 ST3GAL1 and ST3GAL2 each became highly expressed during the differentiation of iPSCs to HPCs but decreased markedly in their expression upon differentiation into MKs, suggesting coordination of expression during megakaryopoiesis. 35507766 5 61 theme glycan 1054:1059 arg1 chains 1061:1066 unsialylated Galβ1,3GalNAc glycan chains 1027:1066 unsialylated Galβ1,3GalNAc glycan chains 1027:1066 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 1 62 gly glycosylated 308:319 arg1 proteins 321:328 O-linked glycosylated proteins 299:328 O-linked glycosylated proteins 299:328 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 8 63 theme ST3GAL2 1609:1615 arg1 disruption 1583:1592 disruption 1583:1592 disruption of ST3GAL1 and ST3GAL2 1583:1615 Finally, although disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. 35507766 9 64 link O-linked 1830:1837 arg1 sialylation 1846:1856 O-linked glycan sialylation 1830:1856 O-linked glycan sialylation in hemato- and megakaryocytopoiesis 1830:1892 Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis. 35507766 2 65 from role 401:404 arg1 O-sialylation 420:432 O-sialylation 420:432 O-sialylation 420:432 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 1 66 theme type 235:238 arg1 in vitro 274:281 type III disaccharides (Galβ1,3GalNAc) in vitro 235:281 type III disaccharides (Galβ1,3GalNAc) in vitro 235:281 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 6 67 theme HPC 1339:1341 arg1 CD34 1351:1354 CD34 1351:1354 CD34 1351:1354 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 67 theme HPC 1339:1341 arg1 substrates 1442:1451 major GP substrates 1433:1451 major GP substrates for ST3GAL1 and ST3GAL2 1433:1475 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 67 theme HPC 1339:1341 arg1 markers 1343:1349 the HPC markers CD34 and CD43 1335:1363 the HPC markers CD34 and CD43 1335:1363 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 67 theme HPC 1339:1341 arg1 CD43 1360:1363 CD43 1360:1363 CD43 1360:1363 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 67 theme HPC 1339:1341 arg1 GPIbα 1407:1411 MK membrane glycoprotein (GP) GPIbα 1377:1411 MK membrane glycoprotein (GP) GPIbα 1377:1411 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 1 68 link O-linked 299:306 arg1 proteins 321:328 O-linked glycosylated proteins 299:328 O-linked glycosylated proteins 299:328 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 3 69 dep became 627:632 arg1 each 622:625 each 622:625 each 622:625 ST3GAL1 and ST3GAL2 each became highly expressed during the differentiation of iPSCs to HPCs but decreased markedly in their expression upon differentiation into MKs, suggesting coordination of expression during megakaryopoiesis. 35507766 5 70 attach derived 1108:1114 arg2 MKs 1104:1106 MKs 1104:1106 MKs derived from double-knockout iPSCs 1104:1141 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 5 70 attach derived 1108:1114 arg1 iPSCs 1137:1141 double-knockout iPSCs 1121:1141 double-knockout iPSCs 1121:1141 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 1 71 theme disaccharides 244:256 arg1 in vitro 274:281 type III disaccharides (Galβ1,3GalNAc) in vitro 235:281 type III disaccharides (Galβ1,3GalNAc) in vitro 235:281 Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. 35507766 2 72 theme cells 519:523 arg1 differentiation 469:483 differentiation 469:483 differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs) 469:599 To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). 35507766 6 73 theme major 1433:1437 arg1 substrates 1442:1451 major GP substrates 1433:1451 major GP substrates for ST3GAL1 and ST3GAL2 1433:1475 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 73 theme major 1433:1437 arg1 markers 1343:1349 the HPC markers CD34 and CD43 1335:1363 the HPC markers CD34 and CD43 1335:1363 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 73 theme major 1433:1437 arg1 GPIbα 1407:1411 MK membrane glycoprotein (GP) GPIbα 1377:1411 MK membrane glycoprotein (GP) GPIbα 1377:1411 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 74 dep markers 1343:1349 arg1 CD34 1351:1354 CD34 1351:1354 CD34 1351:1354 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 74 dep markers 1343:1349 arg1 markers 1343:1349 the HPC markers CD34 and CD43 1335:1363 the HPC markers CD34 and CD43 1335:1363 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 74 dep markers 1343:1349 arg1 CD43 1360:1363 CD43 1360:1363 CD43 1360:1363 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 5 75 theme functional 1271:1280 arg1 sialyltransferases 1300:1317 functional cellular O-glycan sialyltransferases 1271:1317 functional cellular O-glycan sialyltransferases 1271:1317 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 5 75 theme functional 1271:1280 arg1 both 1253:1256 both 1253:1256 both 1253:1256 Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. 35507766 6 76 theme membrane 1380:1387 arg1 GP 1403:1404 GP 1403:1404 GP 1403:1404 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 35507766 6 76 theme membrane 1380:1387 arg1 glycoprotein 1389:1400 MK membrane glycoprotein 1377:1400 MK membrane glycoprotein (GP) GPIbα 1377:1411 Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. 36538968 2 0 link N-linked 371:378 arg1 glycosylation 380:392 N-linked glycosylation 371:392 N-linked glycosylation 371:392 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 1 1 theme fine-tune 276:284 arg1 processes 297:305 fine-tune biological processes 276:305 fine-tune biological processes 276:305 Diverse post-translational modifications (PTMs) regulate protein function and interaction to fine-tune biological processes. 36538968 4 2 theme labeling 913:920 arg1 combination 889:899 a combination 887:899 a combination of chemical labeling and titanium dioxide (TiO2) chromatography 887:963 This strategy, termed TiCPG, is based on a combination of chemical labeling and titanium dioxide (TiO2) chromatography. 36538968 12 3 theme signaling 2151:2159 arg1 events 2161:2166 known cellular signaling events 2136:2166 known cellular signaling events of proinflammatory cytokine effect on beta-cells 2136:2215 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 5 4 from proteome 1009:1016 arg1 β-cells 1048:1054 β-cells 1048:1054 β-cells subject to pro-inflammatory cytokines stimulation 1048:1104 We applied the TiCPG strategy to study the proteome and the three PTMs changes in β-cells subject to pro-inflammatory cytokines stimulation. 36538968 1 5 theme Diverse 183:189 arg1 PTMs 225:228 PTMs 225:228 PTMs 225:228 Diverse post-translational modifications (PTMs) regulate protein function and interaction to fine-tune biological processes. 36538968 1 5 theme Diverse 183:189 arg1 modifications 210:222 Diverse post-translational modifications 183:222 Diverse post-translational modifications (PTMs) 183:229 Diverse post-translational modifications (PTMs) regulate protein function and interaction to fine-tune biological processes. 36538968 6 6 theme sialylated 1189:1198 arg1 N-glycosites 1200:1211 962 sialylated N-glycosites 1185:1211 962 sialylated N-glycosites from 5496 proteins 1185:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 6 7 gly sialylated 1189:1198 arg1 N-glycosites 1200:1211 962 sialylated N-glycosites 1185:1211 962 sialylated N-glycosites from 5496 proteins 1185:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 2 8 theme Cys 347:349 arg1 modifications 352:364 cysteines (Cys) modifications 336:364 cysteines (Cys) modifications 336:364 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 11 9 contain have 2024:2027 arg1 younger 1976:1982 younger 1976:1982 younger 1976:1982 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 11 9 contain have 2024:2027 arg1 researchers 2000:2010 researchers 2000:2010 researchers 2000:2010 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 11 9 contain have 2024:2027 arg2 access 2036:2041 direct access 2029:2041 direct access to LC-MSMS 2029:2052 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 3 10 theme sialylated 776:785 arg1 glycosylation 796:808 sialylated N-linked glycosylation 776:808 sialylated N-linked glycosylation 776:808 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 2 11 theme cysteines 336:344 arg1 modifications 352:364 cysteines (Cys) modifications 336:364 cysteines (Cys) modifications 336:364 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 12 12 theme known 2136:2140 arg1 events 2161:2166 known cellular signaling events 2136:2166 known cellular signaling events of proinflammatory cytokine effect on beta-cells 2136:2215 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 11 13 theme comprehensive 1843:1855 arg1 knowledge 1873:1881 comprehensive and significant knowledge 1843:1881 comprehensive and significant knowledge on biological systems and cellular signaling 1843:1926 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 0 14 theme N-Glycopeptides 125:139 arg1 enrichment 40:49 the simultaneous enrichment 23:49 the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides 23:139 TiCPG - a strategy for the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides to study cytokines stimulated beta-cells. 36538968 3 15 theme simultaneous 627:638 arg1 characterization 658:673 the simultaneous and comprehensive characterization 623:673 the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material 623:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 4 16 theme titanium 926:933 arg1 dioxide 935:941 titanium dioxide 926:941 titanium dioxide (TiO2) chromatography 926:963 This strategy, termed TiCPG, is based on a combination of chemical labeling and titanium dioxide (TiO2) chromatography. 36538968 4 16 theme titanium 926:933 arg1 TiO2 944:947 TiO2 944:947 TiO2 944:947 This strategy, termed TiCPG, is based on a combination of chemical labeling and titanium dioxide (TiO2) chromatography. 36538968 8 17 theme inducible 1481:1489 arg1 synthase 1494:1501 the inducible NO synthase 1477:1501 the inducible NO synthase 1477:1501 The three PTMs were involved in cytokine mediated β-cell apoptosis, such as the NFκB and the inducible NO synthase signaling pathways. 36538968 10 18 theme quantitative 1720:1731 arg1 assessment 1733:1742 quantitative assessment 1720:1742 quantitative assessment of the proteome 1720:1758 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 3 19 theme low 815:817 arg1 amount 819:824 low amount 815:824 low amount of sample material 815:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 3 19 theme low 815:817 arg1 material 836:843 sample material 829:843 sample material 829:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 5 20 theme subject 1056:1062 arg1 β-cells 1048:1054 β-cells 1048:1054 β-cells subject to pro-inflammatory cytokines stimulation 1048:1104 We applied the TiCPG strategy to study the proteome and the three PTMs changes in β-cells subject to pro-inflammatory cytokines stimulation. 36538968 10 21 theme material 1805:1812 arg1 amount 1788:1793 minimal amount 1780:1793 minimal amount of sample material 1780:1812 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 10 21 theme material 1805:1812 arg1 material 1805:1812 sample material 1798:1812 sample material 1798:1812 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 0 22 gly sialylated 114:123 arg1 N-Glycopeptides 125:139 sialylated N-Glycopeptides 114:139 sialylated N-Glycopeptides 114:139 TiCPG - a strategy for the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides to study cytokines stimulated beta-cells. 36538968 8 23 theme synthase 1494:1501 arg1 pathways 1513:1520 the NFκB and the inducible NO synthase signaling pathways 1464:1520 the NFκB and the inducible NO synthase signaling pathways 1464:1520 The three PTMs were involved in cytokine mediated β-cell apoptosis, such as the NFκB and the inducible NO synthase signaling pathways. 36538968 5 24 theme pro-inflammatory 1067:1082 arg1 cytokines 1084:1092 pro-inflammatory cytokines 1067:1092 pro-inflammatory cytokines stimulation 1067:1104 We applied the TiCPG strategy to study the proteome and the three PTMs changes in β-cells subject to pro-inflammatory cytokines stimulation. 36538968 9 25 theme TiCPG 1536:1540 arg1 tool 1593:1596 a cheap, straightforward, and powerful tool 1554:1596 a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above 1554:1649 Overall, the TiCPG strategy is a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above. 36538968 9 25 theme TiCPG 1536:1540 arg1 strategy 1542:1549 the TiCPG strategy 1532:1549 the TiCPG strategy 1532:1549 Overall, the TiCPG strategy is a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above. 36538968 3 26 link N-linked 787:794 arg1 glycosylation 796:808 sialylated N-linked glycosylation 776:808 sialylated N-linked glycosylation 776:808 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 12 27 theme sub-milligram 2082:2094 arg1 amount 2096:2101 sub-milligram amount 2082:2101 sub-milligram amount of material 2082:2113 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 12 27 theme sub-milligram 2082:2094 arg1 material 2106:2113 material 2106:2113 material 2106:2113 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 11 28 theme low 1944:1946 arg1 time 1957:1960 relatively low analysis time 1933:1960 relatively low analysis time 1933:1960 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 3 29 theme material 836:843 arg1 amount 819:824 low amount 815:824 low amount of sample material 815:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 3 29 theme material 836:843 arg1 material 836:843 sample material 829:843 sample material 829:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 3 30 theme comprehensive 644:656 arg1 characterization 658:673 the simultaneous and comprehensive characterization 623:673 the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material 623:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 10 31 from amount 1788:1793 arg1 PTMs 1770:1773 three PTMs 1764:1773 three PTMs from minimal amount of sample material 1764:1812 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 10 31 from amount 1788:1793 arg1 assessment 1733:1742 quantitative assessment 1720:1742 quantitative assessment of the proteome 1720:1758 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 0 32 theme modified 65:72 arg1 peptides 83:90 reversibly modified cysteine peptides 54:90 reversibly modified cysteine peptides 54:90 TiCPG - a strategy for the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides to study cytokines stimulated beta-cells. 36538968 9 33 theme cheap 1556:1560 arg1 tool 1593:1596 a cheap, straightforward, and powerful tool 1554:1596 a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above 1554:1649 Overall, the TiCPG strategy is a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above. 36538968 9 33 theme cheap 1556:1560 arg1 strategy 1542:1549 the TiCPG strategy 1532:1549 the TiCPG strategy 1532:1549 Overall, the TiCPG strategy is a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above. 36538968 12 34 theme known 2264:2268 arg1 pathways 2280:2287 several known signaling pathways 2256:2287 several known signaling pathways 2256:2287 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 0 35 theme peptides 83:90 arg1 enrichment 40:49 the simultaneous enrichment 23:49 the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides 23:139 TiCPG - a strategy for the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides to study cytokines stimulated beta-cells. 36538968 9 36 theme straightforward 1563:1577 arg1 tool 1593:1596 a cheap, straightforward, and powerful tool 1554:1596 a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above 1554:1649 Overall, the TiCPG strategy is a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above. 36538968 9 36 theme straightforward 1563:1577 arg1 strategy 1542:1549 the TiCPG strategy 1532:1549 the TiCPG strategy 1532:1549 Overall, the TiCPG strategy is a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above. 36538968 2 37 theme β-cell 552:557 arg1 death 559:563 pancreatic β-cell death 541:563 pancreatic β-cell death 541:563 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 2 38 theme signaling 435:443 arg1 those 463:467 those 463:467 those 463:467 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 2 38 theme signaling 435:443 arg1 pathways 445:452 cellular signaling pathways 426:452 cellular signaling pathways 426:452 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 0 39 theme phosphopeptides 93:107 arg1 enrichment 40:49 the simultaneous enrichment 23:49 the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides 23:139 TiCPG - a strategy for the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides to study cytokines stimulated beta-cells. 36538968 3 40 gly sialylated 776:785 arg1 glycosylation 796:808 sialylated N-linked glycosylation 776:808 sialylated N-linked glycosylation 776:808 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 11 41 from knowledge 1873:1881 arg1 systems 1897:1903 biological systems 1886:1903 biological systems 1886:1903 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 11 41 from knowledge 1873:1881 arg1 signaling 1918:1926 cellular signaling 1909:1926 cellular signaling 1909:1926 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 8 42 theme cytokine 1420:1427 arg1 apoptosis 1445:1453 cytokine mediated β-cell apoptosis 1420:1453 cytokine mediated β-cell apoptosis 1420:1453 The three PTMs were involved in cytokine mediated β-cell apoptosis, such as the NFκB and the inducible NO synthase signaling pathways. 36538968 11 43 theme suitable 1963:1970 arg1 time 1957:1960 relatively low analysis time 1933:1960 relatively low analysis time 1933:1960 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 11 44 theme direct 2029:2034 arg1 access 2036:2041 direct access 2029:2041 direct access to LC-MSMS 2029:2052 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 5 45 theme TiCPG 981:985 arg1 strategy 987:994 the TiCPG strategy 977:994 the TiCPG strategy to study the proteome and the three PTMs changes in β-cells subject to pro-inflammatory cytokines stimulation 977:1104 We applied the TiCPG strategy to study the proteome and the three PTMs changes in β-cells subject to pro-inflammatory cytokines stimulation. 36538968 2 46 theme cytokines 513:521 arg1 action 486:491 the action 482:491 the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes 482:576 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 2 47 gly glycosylation 380:392 arg1 those 463:467 those 463:467 those 463:467 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 2 47 gly glycosylation 380:392 arg1 pathways 445:452 cellular signaling pathways 426:452 cellular signaling pathways 426:452 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 8 48 theme β-cell 1438:1443 arg1 apoptosis 1445:1453 cytokine mediated β-cell apoptosis 1420:1453 cytokine mediated β-cell apoptosis 1420:1453 The three PTMs were involved in cytokine mediated β-cell apoptosis, such as the NFκB and the inducible NO synthase signaling pathways. 36538968 3 49 theme proteome 682:689 arg1 characterization 658:673 the simultaneous and comprehensive characterization 623:673 the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material 623:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 2 50 theme N-linked 371:378 arg1 glycosylation 380:392 N-linked glycosylation 371:392 N-linked glycosylation 371:392 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 0 51 theme simultaneous 27:38 arg1 enrichment 40:49 the simultaneous enrichment 23:49 the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides 23:139 TiCPG - a strategy for the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides to study cytokines stimulated beta-cells. 36538968 12 52 dep able 2124:2127 arg1 map 2132:2134 map 2132:2134 to map known cellular signaling events of proinflammatory cytokine effect on beta-cells 2129:2215 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 12 52 dep able 2124:2127 arg1 discover 2224:2231 discover 2224:2231 to discover novel PTMs involved in several known signaling pathways 2221:2287 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 7 53 theme PTM 1318:1320 arg1 isoforms 1330:1337 3020 PTM peptide isoforms 1313:1337 3020 PTM peptide isoforms from 1468 proteins 1313:1356 Significant regulation was found on 100 proteins at the expression level, while 3020 PTM peptide isoforms from 1468 proteins were significantly regulated. 36538968 3 54 theme modified 727:734 arg1 rmCys 747:751 rmCys 747:751 rmCys 747:751 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 3 54 theme modified 727:734 arg1 Cysteines 736:744 reversibly modified Cysteines 716:744 reversibly modified Cysteines (rmCys) 716:752 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 12 55 theme cytokine 2187:2194 arg1 effect 2196:2201 proinflammatory cytokine effect 2171:2201 proinflammatory cytokine effect on beta-cells 2171:2215 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 11 56 theme significant 1861:1871 arg1 knowledge 1873:1881 comprehensive and significant knowledge 1843:1881 comprehensive and significant knowledge on biological systems and cellular signaling 1843:1926 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 1 57 theme protein 240:246 arg1 function 248:255 protein function 240:255 protein function 240:255 Diverse post-translational modifications (PTMs) regulate protein function and interaction to fine-tune biological processes. 36538968 7 58 from proteins 1349:1356 arg1 isoforms 1330:1337 3020 PTM peptide isoforms 1313:1337 3020 PTM peptide isoforms from 1468 proteins 1313:1356 Significant regulation was found on 100 proteins at the expression level, while 3020 PTM peptide isoforms from 1468 proteins were significantly regulated. 36538968 6 59 theme rmCys 1148:1152 arg1 sites 1154:1158 8346 rmCys sites 1143:1158 8346 rmCys sites 1143:1158 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 8 60 theme NFκB 1468:1471 arg1 pathways 1513:1520 the NFκB and the inducible NO synthase signaling pathways 1464:1520 the NFκB and the inducible NO synthase signaling pathways 1464:1520 The three PTMs were involved in cytokine mediated β-cell apoptosis, such as the NFκB and the inducible NO synthase signaling pathways. 36538968 10 61 theme proteome 1751:1758 arg1 PTMs 1770:1773 three PTMs 1764:1773 three PTMs from minimal amount of sample material 1764:1812 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 10 61 theme proteome 1751:1758 arg1 assessment 1733:1742 quantitative assessment 1720:1742 quantitative assessment of the proteome 1720:1758 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 12 62 from beta-cells 2206:2215 arg1 events 2161:2166 known cellular signaling events 2136:2166 known cellular signaling events of proinflammatory cytokine effect on beta-cells 2136:2215 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 0 63 dep TiCPG 0:4 arg1 study 144:148 study 144:148 to study cytokines 141:158 TiCPG - a strategy for the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides to study cytokines stimulated beta-cells. 36538968 7 64 located found 1260:1264 arg2 regulation 1245:1254 Significant regulation 1233:1254 Significant regulation 1233:1254 Significant regulation was found on 100 proteins at the expression level, while 3020 PTM peptide isoforms from 1468 proteins were significantly regulated. 36538968 7 64 located found 1260:1264 arg1 level 1300:1304 the expression level 1285:1304 the expression level 1285:1304 Significant regulation was found on 100 proteins at the expression level, while 3020 PTM peptide isoforms from 1468 proteins were significantly regulated. 36538968 7 64 located found 1260:1264 arg1 proteins 1273:1280 100 proteins 1269:1280 100 proteins 1269:1280 Significant regulation was found on 100 proteins at the expression level, while 3020 PTM peptide isoforms from 1468 proteins were significantly regulated. 36538968 12 65 from effect 2196:2201 arg1 beta-cells 2206:2215 beta-cells 2206:2215 beta-cells 2206:2215 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 6 66 theme quantitative 1118:1129 arg1 analysis 1131:1138 quantitative analysis 1118:1138 quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins 1118:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 11 67 theme analysis 1948:1955 arg1 time 1957:1960 relatively low analysis time 1933:1960 relatively low analysis time 1933:1960 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 1 68 theme biological 286:295 arg1 processes 297:305 fine-tune biological processes 276:305 fine-tune biological processes 276:305 Diverse post-translational modifications (PTMs) regulate protein function and interaction to fine-tune biological processes. 36538968 4 69 theme chemical 904:911 arg1 labeling 913:920 chemical labeling 904:920 chemical labeling 904:920 This strategy, termed TiCPG, is based on a combination of chemical labeling and titanium dioxide (TiO2) chromatography. 36538968 6 70 theme 5496 1218:1221 arg1 proteins 1223:1230 5496 proteins 1218:1230 5496 proteins 1218:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 7 71 theme 3020 1313:1316 arg1 isoforms 1330:1337 3020 PTM peptide isoforms 1313:1337 3020 PTM peptide isoforms from 1468 proteins 1313:1356 Significant regulation was found on 100 proteins at the expression level, while 3020 PTM peptide isoforms from 1468 proteins were significantly regulated. 36538968 2 72 theme Reversible 308:317 arg1 phosphorylation 319:333 Reversible phosphorylation 308:333 Reversible phosphorylation 308:333 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 11 73 dep younger 1976:1982 arg1 researchers 1984:1994 researchers 1984:1994 researchers 1984:1994 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 6 74 theme N-glycosites 1200:1211 arg1 analysis 1131:1138 quantitative analysis 1118:1138 quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins 1118:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 12 75 theme cellular 2142:2149 arg1 events 2161:2166 known cellular signaling events 2136:2166 known cellular signaling events of proinflammatory cytokine effect on beta-cells 2136:2215 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 10 76 theme sample 1798:1803 arg1 material 1805:1812 sample material 1798:1812 sample material 1798:1812 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 1 77 theme post-translational 191:208 arg1 PTMs 225:228 PTMs 225:228 PTMs 225:228 Diverse post-translational modifications (PTMs) regulate protein function and interaction to fine-tune biological processes. 36538968 1 77 theme post-translational 191:208 arg1 modifications 210:222 Diverse post-translational modifications 183:222 Diverse post-translational modifications (PTMs) 183:229 Diverse post-translational modifications (PTMs) regulate protein function and interaction to fine-tune biological processes. 36538968 11 78 theme simple 1820:1825 arg1 method 1827:1832 This simple method 1815:1832 This simple method 1815:1832 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 0 79 theme sialylated 114:123 arg1 N-Glycopeptides 125:139 sialylated N-Glycopeptides 114:139 sialylated N-Glycopeptides 114:139 TiCPG - a strategy for the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides to study cytokines stimulated beta-cells. 36538968 3 80 theme novel 604:608 arg1 strategy 610:617 a novel strategy 602:617 a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material 602:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 6 81 theme phosphosites 1168:1179 arg1 analysis 1131:1138 quantitative analysis 1118:1138 quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins 1118:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 3 82 theme N-linked 787:794 arg1 glycosylation 796:808 sialylated N-linked glycosylation 776:808 sialylated N-linked glycosylation 776:808 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 5 83 from changes 1037:1043 arg1 β-cells 1048:1054 β-cells 1048:1054 β-cells subject to pro-inflammatory cytokines stimulation 1048:1104 We applied the TiCPG strategy to study the proteome and the three PTMs changes in β-cells subject to pro-inflammatory cytokines stimulation. 36538968 4 84 theme chromatography 950:963 arg1 combination 889:899 a combination 887:899 a combination of chemical labeling and titanium dioxide (TiO2) chromatography 887:963 This strategy, termed TiCPG, is based on a combination of chemical labeling and titanium dioxide (TiO2) chromatography. 36538968 8 85 theme NO 1491:1492 arg1 synthase 1494:1501 the inducible NO synthase 1477:1501 the inducible NO synthase 1477:1501 The three PTMs were involved in cytokine mediated β-cell apoptosis, such as the NFκB and the inducible NO synthase signaling pathways. 36538968 6 86 gly N-glycosites 1200:1211 arg2 N-glycosites 1200:1211 962 sialylated N-glycosites 1185:1211 962 sialylated N-glycosites from 5496 proteins 1185:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 3 87 theme sample 829:834 arg1 material 836:843 sample material 829:843 sample material 829:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 8 88 theme signaling 1503:1511 arg1 pathways 1513:1520 the NFκB and the inducible NO synthase signaling pathways 1464:1520 the NFκB and the inducible NO synthase signaling pathways 1464:1520 The three PTMs were involved in cytokine mediated β-cell apoptosis, such as the NFκB and the inducible NO synthase signaling pathways. 36538968 12 89 theme material 2106:2113 arg1 amount 2096:2101 sub-milligram amount 2082:2101 sub-milligram amount of material 2082:2113 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 12 89 theme material 2106:2113 arg1 material 2106:2113 material 2106:2113 material 2106:2113 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 4 90 theme dioxide 935:941 arg1 chromatography 950:963 titanium dioxide (TiO2) chromatography 926:963 titanium dioxide (TiO2) chromatography 926:963 This strategy, termed TiCPG, is based on a combination of chemical labeling and titanium dioxide (TiO2) chromatography. 36538968 5 91 theme cytokines 1084:1092 arg1 stimulation 1094:1104 pro-inflammatory cytokines stimulation 1067:1104 pro-inflammatory cytokines stimulation 1067:1104 We applied the TiCPG strategy to study the proteome and the three PTMs changes in β-cells subject to pro-inflammatory cytokines stimulation. 36538968 12 92 from amount 2096:2101 arg1 able 2124:2127 able 2124:2127 able 2124:2127 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 0 93 theme cysteine 74:81 arg1 peptides 83:90 reversibly modified cysteine peptides 54:90 reversibly modified cysteine peptides 54:90 TiCPG - a strategy for the simultaneous enrichment of reversibly modified cysteine peptides, phosphopeptides, and sialylated N-Glycopeptides to study cytokines stimulated beta-cells. 36538968 3 94 from amount 819:824 arg1 phosphorylation 755:769 phosphorylation 755:769 phosphorylation 755:769 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 3 94 from amount 819:824 arg1 proteome 682:689 the proteome 678:689 the proteome 678:689 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 3 94 from amount 819:824 arg1 Cysteines 736:744 reversibly modified Cysteines 716:744 reversibly modified Cysteines (rmCys) 716:752 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 3 94 from amount 819:824 arg1 characterization 658:673 the simultaneous and comprehensive characterization 623:673 the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material 623:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 3 94 from amount 819:824 arg1 PTMs 701:704 three PTMs 695:704 three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material 695:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 3 94 from amount 819:824 arg1 glycosylation 796:808 sialylated N-linked glycosylation 776:808 sialylated N-linked glycosylation 776:808 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 12 95 from events 2161:2166 arg1 beta-cells 2206:2215 beta-cells 2206:2215 beta-cells 2206:2215 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 10 96 theme minimal 1780:1786 arg1 amount 1788:1793 minimal amount 1780:1793 minimal amount of sample material 1780:1812 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 10 96 theme minimal 1780:1786 arg1 material 1805:1812 sample material 1798:1812 sample material 1798:1812 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 12 97 theme several 2256:2262 arg1 pathways 2280:2287 several known signaling pathways 2256:2287 several known signaling pathways 2256:2287 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 2 98 theme pancreatic 541:550 arg1 death 559:563 pancreatic β-cell death 541:563 pancreatic β-cell death 541:563 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 12 99 theme signaling 2270:2278 arg1 pathways 2280:2287 several known signaling pathways 2256:2287 several known signaling pathways 2256:2287 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 3 100 from characterization 658:673 arg1 amount 819:824 low amount 815:824 low amount of sample material 815:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 3 100 from characterization 658:673 arg1 material 836:843 sample material 829:843 sample material 829:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 2 101 theme cellular 426:433 arg1 those 463:467 those 463:467 those 463:467 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 2 101 theme cellular 426:433 arg1 pathways 445:452 cellular signaling pathways 426:452 cellular signaling pathways 426:452 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 9 102 theme powerful 1584:1591 arg1 tool 1593:1596 a cheap, straightforward, and powerful tool 1554:1596 a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above 1554:1649 Overall, the TiCPG strategy is a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above. 36538968 9 102 theme powerful 1584:1591 arg1 strategy 1542:1549 the TiCPG strategy 1532:1549 the TiCPG strategy 1532:1549 Overall, the TiCPG strategy is a cheap, straightforward, and powerful tool for studies targeting the three PTMs described above. 36538968 11 103 theme cellular 1909:1916 arg1 signaling 1918:1926 cellular signaling 1909:1926 cellular signaling 1909:1926 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 12 104 theme novel 2233:2237 arg1 PTMs 2239:2242 novel PTMs 2233:2242 novel PTMs involved in several known signaling pathways 2233:2287 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 10 105 theme fast 1695:1698 arg1 method 1709:1714 a fast and easy method 1693:1714 a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material 1693:1812 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 5 106 theme PTMs 1032:1035 arg1 changes 1037:1043 the three PTMs changes 1022:1043 the three PTMs changes in β-cells subject to pro-inflammatory cytokines stimulation 1022:1104 We applied the TiCPG strategy to study the proteome and the three PTMs changes in β-cells subject to pro-inflammatory cytokines stimulation. 36538968 7 107 theme peptide 1322:1328 arg1 isoforms 1330:1337 3020 PTM peptide isoforms 1313:1337 3020 PTM peptide isoforms from 1468 proteins 1313:1356 Significant regulation was found on 100 proteins at the expression level, while 3020 PTM peptide isoforms from 1468 proteins were significantly regulated. 36538968 2 108 theme pro-inflammatory 496:511 arg1 cytokines 513:521 pro-inflammatory cytokines 496:521 pro-inflammatory cytokines 496:521 Reversible phosphorylation, cysteines (Cys) modifications, and N-linked glycosylation are all essentially involved in cellular signaling pathways, such as those initiated by the action of pro-inflammatory cytokines, which can induce pancreatic β-cell death and diabetes. 36538968 8 109 theme mediated 1429:1436 arg1 apoptosis 1445:1453 cytokine mediated β-cell apoptosis 1420:1453 cytokine mediated β-cell apoptosis 1420:1453 The three PTMs were involved in cytokine mediated β-cell apoptosis, such as the NFκB and the inducible NO synthase signaling pathways. 36538968 7 110 theme Significant 1233:1243 arg1 regulation 1245:1254 Significant regulation 1233:1254 Significant regulation 1233:1254 Significant regulation was found on 100 proteins at the expression level, while 3020 PTM peptide isoforms from 1468 proteins were significantly regulated. 36538968 6 111 theme 10,321 1161:1166 arg1 phosphosites 1168:1179 10,321 phosphosites 1161:1179 10,321 phosphosites 1161:1179 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 11 112 theme biological 1886:1895 arg1 systems 1897:1903 biological systems 1886:1903 biological systems 1886:1903 This simple method provides comprehensive and significant knowledge on biological systems and cellular signaling with relatively low analysis time, suitable for younger researchers and researchers that do not have direct access to LC-MSMS in their laboratories. 36538968 6 113 theme sites 1154:1158 arg1 analysis 1131:1138 quantitative analysis 1118:1138 quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins 1118:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 3 114 theme PTMs 701:704 arg1 characterization 658:673 the simultaneous and comprehensive characterization 623:673 the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material 623:843 Here we have developed a novel strategy for the simultaneous and comprehensive characterization of the proteome and three PTMs including reversibly modified Cysteines (rmCys), phosphorylation, and sialylated N-linked glycosylation from low amount of sample material. 36538968 12 115 theme proinflammatory 2171:2185 arg1 cytokine 2187:2194 proinflammatory cytokine 2171:2194 proinflammatory cytokine effect on beta-cells 2171:2215 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36538968 6 116 from analysis 1131:1138 arg1 proteins 1223:1230 5496 proteins 1218:1230 5496 proteins 1218:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 10 117 theme easy 1704:1707 arg1 method 1709:1714 a fast and easy method 1693:1714 a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material 1693:1812 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 6 118 from proteins 1223:1230 arg1 sites 1154:1158 8346 rmCys sites 1143:1158 8346 rmCys sites 1143:1158 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 6 118 from proteins 1223:1230 arg1 phosphosites 1168:1179 10,321 phosphosites 1161:1179 10,321 phosphosites 1161:1179 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 6 118 from proteins 1223:1230 arg1 analysis 1131:1138 quantitative analysis 1118:1138 quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins 1118:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 6 118 from proteins 1223:1230 arg1 N-glycosites 1200:1211 962 sialylated N-glycosites 1185:1211 962 sialylated N-glycosites from 5496 proteins 1185:1230 It enabled quantitative analysis of 8346 rmCys sites, 10,321 phosphosites and 962 sialylated N-glycosites from 5496 proteins. 36538968 7 119 theme expression 1289:1298 arg1 level 1300:1304 the expression level 1285:1304 the expression level 1285:1304 Significant regulation was found on 100 proteins at the expression level, while 3020 PTM peptide isoforms from 1468 proteins were significantly regulated. 36538968 10 120 theme present 1670:1676 arg1 study 1678:1682 The present study 1666:1682 The present study 1666:1682 SIGNIFICANCE: The present study presents a fast and easy method for quantitative assessment of the proteome and three PTMs from minimal amount of sample material. 36538968 12 121 theme effect 2196:2201 arg1 events 2161:2166 known cellular signaling events 2136:2166 known cellular signaling events of proinflammatory cytokine effect on beta-cells 2136:2215 From sub-milligram amount of material, we were able to map known cellular signaling events of proinflammatory cytokine effect on beta-cells and to discover novel PTMs involved in several known signaling pathways. 36681198 7 0 theme microbial 1059:1067 arg1 diversity 1069:1077 microbial diversity 1059:1077 microbial diversity over time and space 1059:1097 Analysis of microbial diversity over time and space revealed that the dominant bacterium, Comamonas, was replaced by diverse microflora with no obvious dominant genus. 36681198 9 1 theme operating 1350:1358 arg1 BTFs 1360:1363 operating BTFs 1350:1363 operating BTFs with less clogging 1350:1382 This study provides a promising approach to operating BTFs with less clogging. 36681198 7 2 theme diversity 1069:1077 arg1 Analysis 1047:1054 Analysis 1047:1054 Analysis of microbial diversity over time and space 1047:1097 Analysis of microbial diversity over time and space revealed that the dominant bacterium, Comamonas, was replaced by diverse microflora with no obvious dominant genus. 36681198 1 3 theme purify 133:138 arg1 pollutants 140:149 purify pollutants 133:149 purify pollutants 133:149 Bio-trickling filters (BTFs) use an inert filler to purify pollutants making them prone to clogging due to bacterial accumulation. 36681198 7 4 with microflora 1172:1181 arg1 genus 1208:1212 no obvious dominant genus 1188:1212 no obvious dominant genus 1188:1212 Analysis of microbial diversity over time and space revealed that the dominant bacterium, Comamonas, was replaced by diverse microflora with no obvious dominant genus. 36681198 3 5 from state 600:604 arg1 % 588:588 >90% 585:588 >90% 585:588 The BTF was started up within 17 d and restarted within 3 d after starvation for 12-16 d. Its average removal efficiency was >90% at steady state. 36681198 0 6 from Application 0:10 arg1 filter 53:58 a bio-trickling filter 37:58 a bio-trickling filter 37:58 Application of loofah and insects in a bio-trickling filter to relieve clogging. 36681198 4 7 theme m3·h 704:707 arg1 capacity 684:691 a volume capacity 675:691 a volume capacity of 96.2 g·(m3·h)-1 675:710 The maximum elimination capacity of 86.4 g·(m3·h)-1 was obtained at a volume capacity of 96.2 g·(m3·h)-1. 36681198 2 8 with cooperation 280:290 arg1 insects 297:303 insects 297:303 insects 297:303 To investigate the performance of a non-inert filler in BTF and its cooperation with insects to relieve clogging, a vertical BTF was constructed with a loofah/Pall ring/polydimethylsiloxane composite filler and selected bacteria to purify toluene. 36681198 2 9 theme filler 258:263 arg1 performance 231:241 the performance 227:241 the performance of a non-inert filler in BTF 227:270 To investigate the performance of a non-inert filler in BTF and its cooperation with insects to relieve clogging, a vertical BTF was constructed with a loofah/Pall ring/polydimethylsiloxane composite filler and selected bacteria to purify toluene. 36681198 8 10 theme loofah 1239:1244 arg1 migration 1246:1254 loofah migration 1239:1254 loofah migration 1239:1254 Insect introduction and loofah migration had little effect on the evolution of microflora. 36681198 2 11 theme non-inert 248:256 arg1 filler 258:263 a non-inert filler 246:263 a non-inert filler 246:263 To investigate the performance of a non-inert filler in BTF and its cooperation with insects to relieve clogging, a vertical BTF was constructed with a loofah/Pall ring/polydimethylsiloxane composite filler and selected bacteria to purify toluene. 36681198 4 12 theme 86.4 g· 643:649 arg1 capacity 631:638 The maximum elimination capacity 607:638 The maximum elimination capacity of 86.4 g·(m3·h)-1 607:657 The maximum elimination capacity of 86.4 g·(m3·h)-1 was obtained at a volume capacity of 96.2 g·(m3·h)-1. 36681198 9 13 theme less 1370:1373 arg1 clogging 1375:1382 less clogging 1370:1382 less clogging 1370:1382 This study provides a promising approach to operating BTFs with less clogging. 36681198 7 14 theme dominant 1117:1124 arg1 Comamonas 1137:1145 Comamonas 1137:1145 Comamonas 1137:1145 Analysis of microbial diversity over time and space revealed that the dominant bacterium, Comamonas, was replaced by diverse microflora with no obvious dominant genus. 36681198 7 14 theme dominant 1117:1124 arg1 bacterium 1126:1134 the dominant bacterium 1113:1134 the dominant bacterium 1113:1134 Analysis of microbial diversity over time and space revealed that the dominant bacterium, Comamonas, was replaced by diverse microflora with no obvious dominant genus. 36681198 3 15 dep removal 562:568 arg1 % 588:588 >90% 585:588 >90% 585:588 The BTF was started up within 17 d and restarted within 3 d after starvation for 12-16 d. Its average removal efficiency was >90% at steady state. 36681198 5 16 theme holometabolous 733:746 arg1 insects 748:754 holometabolous insects 733:754 holometabolous insects (Clogmia albipunctata) 733:777 The introduction of holometabolous insects (Clogmia albipunctata) rapidly removed the biofilm and accelerated the degradation of the loofah, which alleviated clogging. 36681198 5 16 theme holometabolous 733:746 arg1 albipunctata 765:776 albipunctata 765:776 albipunctata 765:776 The introduction of holometabolous insects (Clogmia albipunctata) rapidly removed the biofilm and accelerated the degradation of the loofah, which alleviated clogging. 36681198 4 17 theme maximum 611:617 arg1 capacity 631:638 The maximum elimination capacity 607:638 The maximum elimination capacity of 86.4 g·(m3·h)-1 607:657 The maximum elimination capacity of 86.4 g·(m3·h)-1 was obtained at a volume capacity of 96.2 g·(m3·h)-1. 36681198 5 18 theme insects 748:754 arg1 introduction 717:728 The introduction 713:728 The introduction of holometabolous insects (Clogmia albipunctata) 713:777 The introduction of holometabolous insects (Clogmia albipunctata) rapidly removed the biofilm and accelerated the degradation of the loofah, which alleviated clogging. 36681198 6 19 theme microscope 918:927 arg1 observations 936:947 confocal laser scanning microscope (CLSM) observations 894:947 confocal laser scanning microscope (CLSM) observations 894:947 Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. 36681198 1 20 theme Bio-trickling 81:93 arg1 BTFs 104:107 BTFs 104:107 BTFs 104:107 Bio-trickling filters (BTFs) use an inert filler to purify pollutants making them prone to clogging due to bacterial accumulation. 36681198 1 20 theme Bio-trickling 81:93 arg1 filters 95:101 Bio-trickling filters 81:101 Bio-trickling filters (BTFs) 81:108 Bio-trickling filters (BTFs) use an inert filler to purify pollutants making them prone to clogging due to bacterial accumulation. 36681198 6 21 theme scanning 909:916 arg1 CLSM 930:933 CLSM 930:933 CLSM 930:933 Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. 36681198 6 21 theme scanning 909:916 arg1 microscope 918:927 confocal laser scanning microscope 894:927 confocal laser scanning microscope (CLSM) observations 894:947 Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. 36681198 4 22 theme 96.2 g· 696:702 arg1 m3·h 704:707 96.2 g·(m3·h)-1 696:710 96.2 g·(m3·h)-1 696:710 The maximum elimination capacity of 86.4 g·(m3·h)-1 was obtained at a volume capacity of 96.2 g·(m3·h)-1. 36681198 2 23 theme composite 402:410 arg1 filler 412:417 a loofah/Pall ring/polydimethylsiloxane composite filler 362:417 a loofah/Pall ring/polydimethylsiloxane composite filler 362:417 To investigate the performance of a non-inert filler in BTF and its cooperation with insects to relieve clogging, a vertical BTF was constructed with a loofah/Pall ring/polydimethylsiloxane composite filler and selected bacteria to purify toluene. 36681198 4 24 theme volume 677:682 arg1 capacity 684:691 a volume capacity 675:691 a volume capacity of 96.2 g·(m3·h)-1 675:710 The maximum elimination capacity of 86.4 g·(m3·h)-1 was obtained at a volume capacity of 96.2 g·(m3·h)-1. 36681198 6 25 theme laser 903:907 arg1 CLSM 930:933 CLSM 930:933 CLSM 930:933 Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. 36681198 6 25 theme laser 903:907 arg1 microscope 918:927 confocal laser scanning microscope 894:927 confocal laser scanning microscope (CLSM) observations 894:947 Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. 36681198 8 26 theme microflora 1294:1303 arg1 evolution 1281:1289 the evolution 1277:1289 the evolution of microflora 1277:1303 Insect introduction and loofah migration had little effect on the evolution of microflora. 36681198 2 27 theme ring/polydimethylsiloxane 376:400 arg1 filler 412:417 a loofah/Pall ring/polydimethylsiloxane composite filler 362:417 a loofah/Pall ring/polydimethylsiloxane composite filler 362:417 To investigate the performance of a non-inert filler in BTF and its cooperation with insects to relieve clogging, a vertical BTF was constructed with a loofah/Pall ring/polydimethylsiloxane composite filler and selected bacteria to purify toluene. 36681198 6 28 theme confocal 894:901 arg1 CLSM 930:933 CLSM 930:933 CLSM 930:933 Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. 36681198 6 28 theme confocal 894:901 arg1 microscope 918:927 confocal laser scanning microscope 894:927 confocal laser scanning microscope (CLSM) observations 894:947 Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. 36681198 8 29 contain had 1256:1258 arg1 migration 1246:1254 loofah migration 1239:1254 loofah migration 1239:1254 Insect introduction and loofah migration had little effect on the evolution of microflora. 36681198 8 29 contain had 1256:1258 arg1 introduction 1222:1233 Insect introduction 1215:1233 Insect introduction 1215:1233 Insect introduction and loofah migration had little effect on the evolution of microflora. 36681198 8 29 contain had 1256:1258 arg2 effect 1267:1272 little effect 1260:1272 little effect 1260:1272 Insect introduction and loofah migration had little effect on the evolution of microflora. 36681198 1 30 theme due 181:183 arg1 clogging 172:179 clogging 172:179 clogging due to bacterial accumulation 172:209 Bio-trickling filters (BTFs) use an inert filler to purify pollutants making them prone to clogging due to bacterial accumulation. 36681198 8 31 theme little 1260:1265 arg1 effect 1267:1272 little effect 1260:1272 little effect 1260:1272 Insect introduction and loofah migration had little effect on the evolution of microflora. 36681198 2 32 from performance 231:241 arg1 BTF 268:270 BTF 268:270 BTF 268:270 To investigate the performance of a non-inert filler in BTF and its cooperation with insects to relieve clogging, a vertical BTF was constructed with a loofah/Pall ring/polydimethylsiloxane composite filler and selected bacteria to purify toluene. 36681198 2 33 theme loofah/Pall 364:374 arg1 filler 412:417 a loofah/Pall ring/polydimethylsiloxane composite filler 362:417 a loofah/Pall ring/polydimethylsiloxane composite filler 362:417 To investigate the performance of a non-inert filler in BTF and its cooperation with insects to relieve clogging, a vertical BTF was constructed with a loofah/Pall ring/polydimethylsiloxane composite filler and selected bacteria to purify toluene. 36681198 0 34 theme insects 26:32 arg1 Application 0:10 Application 0:10 Application of loofah and insects in a bio-trickling filter 0:58 Application of loofah and insects in a bio-trickling filter to relieve clogging. 36681198 8 35 theme Insect 1215:1220 arg1 introduction 1222:1233 Insect introduction 1215:1233 Insect introduction 1215:1233 Insect introduction and loofah migration had little effect on the evolution of microflora. 36681198 0 36 theme bio-trickling 39:51 arg1 filter 53:58 a bio-trickling filter 37:58 a bio-trickling filter 37:58 Application of loofah and insects in a bio-trickling filter to relieve clogging. 36681198 3 37 theme average 554:560 arg1 removal 562:568 Its average removal efficiency was >90% at steady state 550:604 Its average removal efficiency was >90% at steady state 550:604 The BTF was started up within 17 d and restarted within 3 d after starvation for 12-16 d. Its average removal efficiency was >90% at steady state. 36681198 5 38 theme loofah 846:851 arg1 degradation 827:837 the degradation 823:837 the degradation of the loofah, which alleviated clogging 823:878 The introduction of holometabolous insects (Clogmia albipunctata) rapidly removed the biofilm and accelerated the degradation of the loofah, which alleviated clogging. 36681198 1 39 theme inert 117:121 arg1 filler 123:128 an inert filler 114:128 an inert filler to purify pollutants 114:149 Bio-trickling filters (BTFs) use an inert filler to purify pollutants making them prone to clogging due to bacterial accumulation. 36681198 9 40 with BTFs 1360:1363 arg1 clogging 1375:1382 less clogging 1370:1382 less clogging 1370:1382 This study provides a promising approach to operating BTFs with less clogging. 36681198 7 41 theme dominant 1199:1206 arg1 genus 1208:1212 no obvious dominant genus 1188:1212 no obvious dominant genus 1188:1212 Analysis of microbial diversity over time and space revealed that the dominant bacterium, Comamonas, was replaced by diverse microflora with no obvious dominant genus. 36681198 1 42 theme bacterial 188:196 arg1 accumulation 198:209 bacterial accumulation 188:209 bacterial accumulation 188:209 Bio-trickling filters (BTFs) use an inert filler to purify pollutants making them prone to clogging due to bacterial accumulation. 36681198 3 43 theme steady 593:598 arg1 state 600:604 steady state 593:604 steady state 593:604 The BTF was started up within 17 d and restarted within 3 d after starvation for 12-16 d. Its average removal efficiency was >90% at steady state. 36681198 7 44 theme obvious 1191:1197 arg1 genus 1208:1212 no obvious dominant genus 1188:1212 no obvious dominant genus 1188:1212 Analysis of microbial diversity over time and space revealed that the dominant bacterium, Comamonas, was replaced by diverse microflora with no obvious dominant genus. 36681198 9 45 theme promising 1328:1336 arg1 approach 1338:1345 a promising approach 1326:1345 a promising approach to operating BTFs with less clogging 1326:1382 This study provides a promising approach to operating BTFs with less clogging. 36681198 2 46 theme vertical 328:335 arg1 BTF 337:339 a vertical BTF 326:339 a vertical BTF 326:339 To investigate the performance of a non-inert filler in BTF and its cooperation with insects to relieve clogging, a vertical BTF was constructed with a loofah/Pall ring/polydimethylsiloxane composite filler and selected bacteria to purify toluene. 36681198 4 47 theme elimination 619:629 arg1 capacity 631:638 The maximum elimination capacity 607:638 The maximum elimination capacity of 86.4 g·(m3·h)-1 607:657 The maximum elimination capacity of 86.4 g·(m3·h)-1 was obtained at a volume capacity of 96.2 g·(m3·h)-1. 36681198 7 48 theme diverse 1164:1170 arg1 microflora 1172:1181 diverse microflora 1164:1181 diverse microflora with no obvious dominant genus 1164:1212 Analysis of microbial diversity over time and space revealed that the dominant bacterium, Comamonas, was replaced by diverse microflora with no obvious dominant genus. 36681198 0 49 theme loofah 15:20 arg1 Application 0:10 Application 0:10 Application of loofah and insects in a bio-trickling filter 0:58 Application of loofah and insects in a bio-trickling filter to relieve clogging. 36681198 6 50 theme biofilm 965:971 arg1 difficult 994:1002 difficult 994:1002 difficult 994:1002 Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. 36681198 6 50 theme biofilm 965:971 arg1 polysaccharides 973:987 the biofilm polysaccharides 961:987 the biofilm polysaccharides 961:987 Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. 35717467 10 0 dep in 1634:1635 arg1 vitro 1637:1641 vitro 1637:1641 vitro 1637:1641 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 6 1 theme complex 974:980 arg1 substrates 982:991 complex substrates 974:991 complex substrates representing dietary fibers and mucin 974:1029 The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. 35717467 10 2 theme key 1574:1576 arg1 microbes 1589:1596 key intestinal microbes 1574:1596 key intestinal microbes 1574:1596 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 10 3 theme present 1473:1479 arg1 study 1481:1485 the present study 1469:1485 the present study 1469:1485 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 2 4 theme key 367:369 arg1 microbes 371:378 key microbes 367:378 key microbes 367:378 The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. 35717467 5 5 theme metabolite 737:746 arg1 measurements 748:759 metabolite measurements 737:759 metabolite measurements 737:759 We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. 35717467 8 6 dep abundance 1249:1257 arg1 the 1245:1247 the 1245:1247 the 1245:1247 The MDb-MM exhibited resistance and resilience to temporal perturbations as evidenced by the abundance and metabolic end products. 35717467 1 7 theme human 179:183 arg1 gut 185:187 the human gut 175:187 the human gut 175:187 Microbe-microbe interactions in the human gut are influenced by host-derived glycans and diet. 35717467 10 8 theme dynamic 1610:1616 arg1 ecosystem 1643:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 0 9 theme minimal 90:96 arg1 microbiome 98:107 a minimal microbiome 88:107 a minimal microbiome exhibiting ecological properties 88:140 Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. 35717467 1 10 link host-derived 207:218 arg1 glycans 220:226 host-derived glycans 207:226 host-derived glycans 207:226 Microbe-microbe interactions in the human gut are influenced by host-derived glycans and diet. 35717467 7 11 theme triplicate 1036:1045 arg1 's 1053:1054 The triplicate MDb-MM's 1032:1054 The triplicate MDb-MM's 1032:1054 The triplicate MDb-MM's followed the Taylor's power law and exhibited strikingly similar ecological and metabolic patterns. 35717467 5 12 theme 16S 695:697 arg1 analysis 727:734 16S rRNA gene-based composition analysis 695:734 16S rRNA gene-based composition analysis 695:734 We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. 35717467 1 13 from interactions 159:170 arg1 gut 185:187 the human gut 175:187 the human gut 175:187 Microbe-microbe interactions in the human gut are influenced by host-derived glycans and diet. 35717467 2 14 theme major 288:292 arg1 challenge 294:302 a major challenge 286:302 a major challenge for unraveling the metabolic interactions and trophic roles of key microbes 286:378 The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. 35717467 8 15 theme end 1273:1275 arg1 products 1277:1284 metabolic end products 1263:1284 metabolic end products 1263:1284 The MDb-MM exhibited resistance and resilience to temporal perturbations as evidenced by the abundance and metabolic end products. 35717467 9 16 theme competitive 1428:1438 arg1 microbiome 1448:1457 a competitive minimal microbiome 1426:1457 a competitive minimal microbiome 1426:1457 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 8 17 theme metabolic 1263:1271 arg1 products 1277:1284 metabolic end products 1263:1284 metabolic end products 1263:1284 The MDb-MM exhibited resistance and resilience to temporal perturbations as evidenced by the abundance and metabolic end products. 35717467 5 18 theme community 800:808 arg1 dynamics 810:817 community dynamics 800:817 community dynamics 800:817 We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. 35717467 9 19 theme minimal 1440:1446 arg1 microbiome 1448:1457 a competitive minimal microbiome 1426:1457 a competitive minimal microbiome 1426:1457 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 9 20 from co-existence 1410:1421 arg1 microbiome 1448:1457 a competitive minimal microbiome 1426:1457 a competitive minimal microbiome 1426:1457 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 9 21 theme Microbe-specific 1287:1302 arg1 dynamics 1313:1320 Microbe-specific temporal dynamics 1287:1320 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network 1287:1385 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 5 22 theme trophic 878:884 arg1 roles 886:890 their trophic roles 872:890 their trophic roles 872:890 We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. 35717467 6 23 theme substrates 982:991 arg1 mixture 963:969 a mixture 961:969 a mixture of complex substrates representing dietary fibers and mucin 961:1029 The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. 35717467 0 24 theme metabolic 8:16 arg1 interactions 18:29 Dynamic metabolic interactions 0:29 Dynamic metabolic interactions 0:29 Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. 35717467 6 25 theme gut 935:937 arg1 ecosystems 939:948 the in vitro gut ecosystems 922:948 the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin 922:1029 The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. 35717467 10 26 theme microbes 1589:1596 arg1 co-existence 1522:1533 the co-existence 1518:1533 the co-existence 1518:1533 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 10 26 theme microbes 1589:1596 arg1 niches 1546:1551 metabolic niches 1536:1551 metabolic niches 1536:1551 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 10 26 theme microbes 1589:1596 arg1 roles 1565:1569 trophic roles 1557:1569 trophic roles 1557:1569 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 9 27 theme temporal 1304:1311 arg1 dynamics 1313:1320 Microbe-specific temporal dynamics 1287:1320 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network 1287:1385 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 2 28 theme metabolic 323:331 arg1 interactions 333:344 metabolic interactions 323:344 metabolic interactions 323:344 The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. 35717467 7 29 theme similar 1113:1119 arg1 patterns 1146:1153 strikingly similar ecological and metabolic patterns 1102:1153 strikingly similar ecological and metabolic patterns 1102:1153 The triplicate MDb-MM's followed the Taylor's power law and exhibited strikingly similar ecological and metabolic patterns. 35717467 0 30 theme Dynamic 0:6 arg1 interactions 18:29 Dynamic metabolic interactions 0:29 Dynamic metabolic interactions 0:29 Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. 35717467 4 31 dep designed 523:530 arg1 based 577:581 based 577:581 based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria 577:680 Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. 35717467 10 32 theme competitive 1622:1632 arg1 ecosystem 1643:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 10 33 theme metabolic 1536:1544 arg1 niches 1546:1551 metabolic niches 1536:1551 metabolic niches 1536:1551 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 2 34 dep interactions 333:344 arg1 the 319:321 the 319:321 the 319:321 The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. 35717467 10 35 theme trophic 1557:1563 arg1 roles 1565:1569 trophic roles 1557:1569 trophic roles 1557:1569 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 6 36 theme in 926:927 arg1 ecosystems 939:948 the in vitro gut ecosystems 922:948 the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin 922:1029 The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. 35717467 3 37 theme Synthetic 381:389 arg1 microbiomes 399:409 Synthetic minimal microbiomes 381:409 Synthetic minimal microbiomes 381:409 Synthetic minimal microbiomes provide a pragmatic approach to investigate their ecology including metabolic interactions. 35717467 4 38 theme Minimal 583:589 arg1 Microbiome 591:600 Minimal Microbiome 583:600 Minimal Microbiome (MDb-MM) 583:609 Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. 35717467 4 38 theme Minimal 583:589 arg1 MDb-MM 603:608 MDb-MM 603:608 MDb-MM 603:608 Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. 35717467 7 39 theme metabolic 1136:1144 arg1 patterns 1146:1153 strikingly similar ecological and metabolic patterns 1102:1153 strikingly similar ecological and metabolic patterns 1102:1153 The triplicate MDb-MM's followed the Taylor's power law and exhibited strikingly similar ecological and metabolic patterns. 35717467 10 40 theme intestinal 1578:1587 arg1 microbes 1589:1596 key intestinal microbes 1574:1596 key intestinal microbes 1574:1596 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 1 41 theme host-derived 207:218 arg1 glycans 220:226 host-derived glycans 207:226 host-derived glycans 207:226 Microbe-microbe interactions in the human gut are influenced by host-derived glycans and diet. 35717467 3 42 theme minimal 391:397 arg1 microbiomes 399:409 Synthetic minimal microbiomes 381:409 Synthetic minimal microbiomes 381:409 Synthetic minimal microbiomes provide a pragmatic approach to investigate their ecology including metabolic interactions. 35717467 0 43 theme ecological 120:129 arg1 properties 131:140 ecological properties 120:140 ecological properties 120:140 Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. 35717467 9 44 theme transcriptional 1325:1339 arg1 niche 1341:1345 transcriptional niche overlap 1325:1353 transcriptional niche overlap 1325:1353 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 10 45 from niches 1546:1551 arg1 ecosystem 1643:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 5 46 theme inter-species 831:843 arg1 interactions 855:866 inter-species metabolic interactions 831:866 inter-species metabolic interactions 831:866 We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. 35717467 7 47 theme ecological 1121:1130 arg1 patterns 1146:1153 strikingly similar ecological and metabolic patterns 1102:1153 strikingly similar ecological and metabolic patterns 1102:1153 The triplicate MDb-MM's followed the Taylor's power law and exhibited strikingly similar ecological and metabolic patterns. 35717467 4 48 theme bacteria 673:680 arg1 features 654:661 known physiological features 634:661 account known physiological features of 16 key bacteria 626:680 Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. 35717467 3 49 theme metabolic 479:487 arg1 interactions 489:500 metabolic interactions 479:500 metabolic interactions 479:500 Synthetic minimal microbiomes provide a pragmatic approach to investigate their ecology including metabolic interactions. 35717467 0 50 theme trophic 35:41 arg1 roles 43:47 trophic roles 35:47 trophic roles of human gut microbes 35:69 Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. 35717467 5 51 theme metabolic 845:853 arg1 interactions 855:866 inter-species metabolic interactions 831:866 inter-species metabolic interactions 831:866 We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. 35717467 6 52 contain containing 950:959 arg1 ecosystems 939:948 the in vitro gut ecosystems 922:948 the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin 922:1029 The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. 35717467 6 52 contain containing 950:959 arg2 mixture 963:969 a mixture 961:969 a mixture of complex substrates representing dietary fibers and mucin 961:1029 The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. 35717467 2 53 theme high 242:245 arg1 complexity 247:256 The high complexity 238:256 The high complexity of the gut microbiome 238:278 The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. 35717467 7 54 theme power 1078:1082 arg1 law 1084:1086 the Taylor's power law 1065:1086 the Taylor's power law 1065:1086 The triplicate MDb-MM's followed the Taylor's power law and exhibited strikingly similar ecological and metabolic patterns. 35717467 4 55 theme key 669:671 arg1 bacteria 673:680 16 key bacteria 666:680 16 key bacteria 666:680 Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. 35717467 0 56 theme human 52:56 arg1 microbes 62:69 human gut microbes 52:69 human gut microbes 52:69 Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. 35717467 5 57 theme rRNA 699:702 arg1 analysis 727:734 16S rRNA gene-based composition analysis 695:734 16S rRNA gene-based composition analysis 695:734 We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. 35717467 8 58 theme temporal 1206:1213 arg1 perturbations 1215:1227 temporal perturbations 1206:1227 temporal perturbations 1206:1227 The MDb-MM exhibited resistance and resilience to temporal perturbations as evidenced by the abundance and metabolic end products. 35717467 10 59 from roles 1565:1569 arg1 ecosystem 1643:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 9 60 from dynamics 1313:1320 arg1 network 1379:1385 trophic interaction network 1359:1385 trophic interaction network 1359:1385 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 9 60 from dynamics 1313:1320 arg1 niche 1341:1345 transcriptional niche overlap 1325:1353 transcriptional niche overlap 1325:1353 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 3 61 theme pragmatic 421:429 arg1 approach 431:438 a pragmatic approach 419:438 a pragmatic approach to investigate their ecology including metabolic interactions 419:500 Synthetic minimal microbiomes provide a pragmatic approach to investigate their ecology including metabolic interactions. 35717467 6 62 theme dietary 1006:1012 arg1 fibers 1014:1019 dietary fibers 1006:1019 dietary fibers 1006:1019 The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. 35717467 5 63 theme gene-based 704:713 arg1 analysis 727:734 16S rRNA gene-based composition analysis 695:734 16S rRNA gene-based composition analysis 695:734 We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. 35717467 9 64 theme trophic 1359:1365 arg1 network 1379:1385 trophic interaction network 1359:1385 trophic interaction network 1359:1385 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 9 65 theme observed 1401:1408 arg1 co-existence 1410:1421 the observed co-existence 1397:1421 the observed co-existence in a competitive minimal microbiome 1397:1457 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 2 66 theme trophic 350:356 arg1 roles 358:362 trophic roles 350:362 trophic roles 350:362 The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. 35717467 6 67 dep in 926:927 arg1 vitro 929:933 vitro 929:933 vitro 929:933 The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. 35717467 5 68 theme composition 715:725 arg1 analysis 727:734 16S rRNA gene-based composition analysis 695:734 16S rRNA gene-based composition analysis 695:734 We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. 35717467 9 69 theme interaction 1367:1377 arg1 network 1379:1385 trophic interaction network 1359:1385 trophic interaction network 1359:1385 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 2 70 theme microbiome 269:278 arg1 complexity 247:256 The high complexity 238:256 The high complexity of the gut microbiome 238:278 The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. 35717467 10 71 from co-existence 1522:1533 arg1 ecosystem 1643:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 4 72 theme known 634:638 arg1 features 654:661 known physiological features 634:661 account known physiological features of 16 key bacteria 626:680 Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. 35717467 10 73 theme in 1634:1635 arg1 ecosystem 1643:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 a highly dynamic and competitive in vitro ecosystem 1601:1651 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 2 74 theme gut 265:267 arg1 microbiome 269:278 the gut microbiome 261:278 the gut microbiome 261:278 The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. 35717467 10 75 theme crucial 1496:1502 arg1 insights 1504:1511 crucial insights 1496:1511 crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem 1496:1651 Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem. 35717467 1 76 theme Microbe-microbe 143:157 arg1 interactions 159:170 Microbe-microbe interactions 143:170 Microbe-microbe interactions in the human gut 143:187 Microbe-microbe interactions in the human gut are influenced by host-derived glycans and diet. 35717467 0 77 theme microbes 62:69 arg1 interactions 18:29 Dynamic metabolic interactions 0:29 Dynamic metabolic interactions 0:29 Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. 35717467 0 77 theme microbes 62:69 arg1 roles 43:47 trophic roles 35:47 trophic roles of human gut microbes 35:69 Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. 35717467 4 78 dep account 626:632 arg1 features 654:661 known physiological features 634:661 account known physiological features of 16 key bacteria 626:680 Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. 35717467 0 79 theme gut 58:60 arg1 microbes 62:69 human gut microbes 52:69 human gut microbes 52:69 Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. 35717467 4 80 theme synthetic 534:542 arg1 microbiome 544:553 a synthetic microbiome 532:553 a synthetic microbiome termed Mucin and Diet 532:575 Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. 35717467 9 81 dep niche 1341:1345 arg1 overlap 1347:1353 overlap 1347:1353 overlap 1347:1353 Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. 35717467 7 82 theme MDb-MM 1047:1052 arg1 's 1053:1054 The triplicate MDb-MM's 1032:1054 The triplicate MDb-MM's 1032:1054 The triplicate MDb-MM's followed the Taylor's power law and exhibited strikingly similar ecological and metabolic patterns. 35717467 2 83 theme microbes 371:378 arg1 interactions 333:344 metabolic interactions 323:344 metabolic interactions 323:344 The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. 35717467 2 83 theme microbes 371:378 arg1 roles 358:362 trophic roles 350:362 trophic roles 350:362 The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. 35717467 4 84 theme physiological 640:652 arg1 features 654:661 known physiological features 634:661 account known physiological features of 16 key bacteria 626:680 Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. 35470857 9 0 theme sialylated 1573:1582 arg1 composition 1590:1600 sialylated mucin composition 1573:1600 sialylated mucin composition 1573:1600 Our results indicate that specific alterations in sialylated mucin composition may be related to impaired cervical sperm transport. 35470857 8 1 theme high 1485:1488 arg1 P < 0.05 1512:1519 P < 0.05 1512:1519 P < 0.05 1512:1519 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 8 1 theme high 1485:1488 arg1 breeds 1504:1509 high fertility ewe breeds 1485:1509 high fertility ewe breeds (P < 0.05) 1485:1520 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 3 2 dep fertility 649:657 arg1 both 632:635 both 632:635 both 632:635 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 6 3 theme ewe 1100:1102 arg1 breed 1104:1108 ewe breed 1100:1108 ewe breed 1100:1108 Biochemical analysis showed that there was an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05). 35470857 8 4 theme ewe 1500:1502 arg1 P < 0.05 1512:1519 P < 0.05 1512:1519 P < 0.05 1512:1519 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 8 4 theme ewe 1500:1502 arg1 breeds 1504:1509 high fertility ewe breeds 1485:1509 high fertility ewe breeds (P < 0.05) 1485:1520 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 6 5 theme higher 1174:1179 arg1 levels 1181:1186 higher levels 1174:1186 higher levels of Neu5,9Ac2 1174:1199 Biochemical analysis showed that there was an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05). 35470857 3 6 from Suffolk 537:543 arg1 Ireland 596:602 Ireland 596:602 Ireland 596:602 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 3 6 from Suffolk 537:543 arg1 Norway 741:746 Norway 741:746 Norway 741:746 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 3 6 from Suffolk 537:543 arg1 NWS 698:700 NWS 698:700 NWS 698:700 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 4 7 from Fur 878:880 arg1 tissue 847:852 cervical tissue 838:852 cervical tissue from Suffolk, Belclare, Fur, and NWS only 838:894 Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. 35470857 4 8 theme acid 780:783 arg1 Expression 749:758 Expression 749:758 Expression of mucin and sialic acid related genes 749:797 Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. 35470857 3 9 theme White 685:689 arg1 Sheep 691:695 White Sheep 685:695 White Sheep 685:695 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 2 10 theme sialylated 280:289 arg1 mucins 300:305 the sialylated cervical mucins 276:305 the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates 276:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 1 11 theme increased 186:194 arg1 viscosity 196:204 the increased viscosity 182:204 the increased viscosity of mucin 182:213 Sialic acid occupies terminal positions on O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport. 35470857 2 12 from differences 373:383 arg1 rates 398:402 pregnancy rates 388:402 pregnancy rates 388:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 5 13 theme secreting 992:1000 arg1 cells 1009:1013 mucin secreting goblet cells 986:1013 mucin secreting goblet cells in the same four ewe breeds 986:1041 Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. 35470857 2 14 theme follicular 312:321 arg1 mucus 329:333 follicular phase mucus 312:333 follicular phase mucus of six European ewe breeds with known differences in pregnancy rates 312:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 4 15 dep mucin 763:767 arg1 genes 793:797 related genes 785:797 related genes 785:797 Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. 35470857 8 16 theme Gene 1312:1315 arg1 analysis 1328:1335 Gene expression analysis 1312:1335 Gene expression analysis 1312:1335 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 7 17 theme goblet 1270:1275 arg1 cells 1277:1281 goblet cells 1270:1281 goblet cells 1270:1281 Suffolk ewes had a lower percentage of goblet cells than Fur and NWS (P < 0.05). 35470857 3 18 theme high 722:725 arg1 fertility 727:735 high fertility 722:735 high fertility 722:735 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 4 19 theme cervical 838:845 arg1 tissue 847:852 cervical tissue 838:852 cervical tissue from Suffolk, Belclare, Fur, and NWS only 838:894 Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. 35470857 5 20 theme epithelial 962:971 arg1 percentage 939:948 the percentage 935:948 the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds 935:1041 Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. 35470857 8 21 theme higher 1348:1353 arg1 expression 1355:1364 higher expression 1348:1364 higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 1348:1403 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 6 22 theme acid 1120:1123 arg1 species 1125:1131 sialic acid species 1113:1131 sialic acid species 1113:1131 Biochemical analysis showed that there was an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05). 35470857 1 23 theme cervical 140:147 arg1 mucins 149:154 cervical mucins 140:154 cervical mucins 140:154 Sialic acid occupies terminal positions on O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport. 35470857 3 24 theme de 609:610 arg1 France 612:617 Ile de France 605:617 Ile de France 605:617 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 2 25 theme estrus 511:516 arg1 cycles 518:523 both synchronized and natural estrus cycles 481:523 cycles 518:523 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 9 26 theme cervical 1629:1636 arg1 transport 1644:1652 impaired cervical sperm transport 1620:1652 impaired cervical sperm transport 1620:1652 Our results indicate that specific alterations in sialylated mucin composition may be related to impaired cervical sperm transport. 35470857 7 27 theme lower 1250:1254 arg1 percentage 1256:1265 a lower percentage 1248:1265 a lower percentage of goblet cells 1248:1281 Suffolk ewes had a lower percentage of goblet cells than Fur and NWS (P < 0.05). 35470857 2 28 theme cervical 414:421 arg1 insemination 434:445 cervical artificial insemination 414:445 cervical artificial insemination (AI) 414:450 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 2 28 theme cervical 414:421 arg1 AI 448:449 AI 448:449 AI 448:449 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 1 29 theme Sialic 84:89 arg1 acid 91:94 Sialic acid 84:94 Sialic acid 84:94 Sialic acid occupies terminal positions on O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport. 35470857 7 30 theme Suffolk 1231:1237 arg1 ewes 1239:1242 Suffolk ewes 1231:1242 Suffolk ewes 1231:1242 Suffolk ewes had a lower percentage of goblet cells than Fur and NWS (P < 0.05). 35470857 8 31 theme ST6GAL2 1397:1403 arg1 expression 1355:1364 higher expression 1348:1364 higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 1348:1403 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 8 31 theme ST6GAL2 1397:1403 arg1 expression 1415:1424 lower expression 1409:1424 lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 1409:1458 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 0 32 theme Biochemical 0:10 arg1 characterization 26:41 Biochemical and molecular characterization 0:41 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 0:82 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 35470857 8 33 theme lower 1409:1413 arg1 expression 1415:1424 lower expression 1409:1424 lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 1409:1458 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 0 34 theme molecular 16:24 arg1 characterization 26:41 Biochemical and molecular characterization 0:41 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 0:82 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 35470857 3 35 theme low 546:548 arg1 Suffolk 537:543 Suffolk 537:543 Suffolk (low fertility) 537:559 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 3 35 theme low 546:548 arg1 fertility 550:558 low fertility 546:558 low fertility 546:558 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 2 36 with breeds 355:360 arg1 differences 373:383 known differences 367:383 known differences in pregnancy rates 367:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 2 37 theme breeds 355:360 arg1 mucus 329:333 follicular phase mucus 312:333 follicular phase mucus of six European ewe breeds with known differences in pregnancy rates 312:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 0 38 theme cervical 57:64 arg1 mucins 66:71 sialylated cervical mucins 46:71 sialylated cervical mucins in sheep† 46:81 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 35470857 8 39 theme MUC5B 1377:1381 arg1 expression 1355:1364 higher expression 1348:1364 higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 1348:1403 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 8 39 theme MUC5B 1377:1381 arg1 expression 1415:1424 lower expression 1409:1424 lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 1409:1458 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 5 40 theme cervical 953:960 arg1 epithelial 962:971 cervical epithelial 953:971 cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds 953:1041 Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. 35470857 6 41 theme Biochemical 1044:1054 arg1 analysis 1056:1063 Biochemical analysis 1044:1063 Biochemical analysis 1044:1063 Biochemical analysis showed that there was an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05). 35470857 2 42 theme European 342:349 arg1 breeds 355:360 six European ewe breeds 338:360 six European ewe breeds with known differences in pregnancy rates 338:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 7 43 contain had 1244:1246 arg1 ewes 1239:1242 Suffolk ewes 1231:1242 Suffolk ewes 1231:1242 Suffolk ewes had a lower percentage of goblet cells than Fur and NWS (P < 0.05). 35470857 7 43 contain had 1244:1246 arg2 percentage 1256:1265 a lower percentage 1248:1265 a lower percentage of goblet cells 1248:1281 Suffolk ewes had a lower percentage of goblet cells than Fur and NWS (P < 0.05). 35470857 0 44 gly sialylated 46:55 arg1 mucins 66:71 sialylated cervical mucins 46:71 sialylated cervical mucins in sheep† 46:81 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 35470857 5 45 theme goblet 1002:1007 arg1 cells 1009:1013 mucin secreting goblet cells 986:1013 mucin secreting goblet cells in the same four ewe breeds 986:1041 Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. 35470857 8 46 theme SIGLEC10 1451:1458 arg1 expression 1355:1364 higher expression 1348:1364 higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 1348:1403 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 8 46 theme SIGLEC10 1451:1458 arg1 expression 1415:1424 lower expression 1409:1424 lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 1409:1458 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 6 47 theme Neu5,9Ac2 1191:1199 arg1 levels 1181:1186 higher levels 1174:1186 higher levels of Neu5,9Ac2 1174:1199 Biochemical analysis showed that there was an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05). 35470857 2 48 theme known 367:371 arg1 differences 373:383 known differences 367:383 known differences in pregnancy rates 367:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 4 49 from NWS 887:889 arg1 tissue 847:852 cervical tissue 838:852 cervical tissue from Suffolk, Belclare, Fur, and NWS only 838:894 Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. 35470857 3 50 with Suffolk 537:543 arg1 fertility 727:735 high fertility 722:735 high fertility 722:735 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 8 51 theme fertility 1490:1498 arg1 P < 0.05 1512:1519 P < 0.05 1512:1519 P < 0.05 1512:1519 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 8 51 theme fertility 1490:1498 arg1 breeds 1504:1509 high fertility ewe breeds 1485:1509 high fertility ewe breeds (P < 0.05) 1485:1520 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 2 52 gly sialylated 280:289 arg1 mucins 300:305 the sialylated cervical mucins 276:305 the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates 276:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 2 53 theme cervical 291:298 arg1 mucins 300:305 the sialylated cervical mucins 276:305 the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates 276:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 4 54 theme sialic 773:778 arg1 acid 780:783 sialic acid 773:783 sialic acid 773:783 Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. 35470857 9 55 theme impaired 1620:1627 arg1 transport 1644:1652 impaired cervical sperm transport 1620:1652 impaired cervical sperm transport 1620:1652 Our results indicate that specific alterations in sialylated mucin composition may be related to impaired cervical sperm transport. 35470857 3 56 theme medium 575:580 arg1 Belclare 565:572 Belclare 565:572 Belclare (medium fertility) 565:591 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 3 56 theme medium 575:580 arg1 fertility 582:590 medium fertility 575:590 medium fertility 575:590 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 3 57 dep Ireland 596:602 arg1 Sheep 691:695 White Sheep 685:695 White Sheep 685:695 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 3 57 dep Ireland 596:602 arg1 both 712:715 both 712:715 both 712:715 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 4 58 theme related 785:791 arg1 genes 793:797 related genes 785:797 related genes 785:797 Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. 35470857 2 59 theme phase 323:327 arg1 mucus 329:333 follicular phase mucus 312:333 follicular phase mucus of six European ewe breeds with known differences in pregnancy rates 312:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 9 60 gly sialylated 1573:1582 arg1 composition 1590:1600 sialylated mucin composition 1573:1600 sialylated mucin composition 1573:1600 Our results indicate that specific alterations in sialylated mucin composition may be related to impaired cervical sperm transport. 35470857 9 61 theme specific 1549:1556 arg1 alterations 1558:1568 specific alterations 1549:1568 specific alterations in sialylated mucin composition 1549:1600 Our results indicate that specific alterations in sialylated mucin composition may be related to impaired cervical sperm transport. 35470857 8 62 theme expression 1317:1326 arg1 analysis 1328:1335 Gene expression analysis 1312:1335 Gene expression analysis 1312:1335 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 4 63 from Belclare 868:875 arg1 tissue 847:852 cervical tissue 838:852 cervical tissue from Suffolk, Belclare, Fur, and NWS only 838:894 Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. 35470857 1 64 theme mucin 209:213 arg1 viscosity 196:204 the increased viscosity 182:204 the increased viscosity of mucin 182:213 Sialic acid occupies terminal positions on O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport. 35470857 0 65 from sheep† 76:81 arg1 characterization 26:41 Biochemical and molecular characterization 0:41 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 0:82 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 35470857 7 66 theme cells 1277:1281 arg1 percentage 1256:1265 a lower percentage 1248:1265 a lower percentage of goblet cells 1248:1281 Suffolk ewes had a lower percentage of goblet cells than Fur and NWS (P < 0.05). 35470857 9 67 theme mucin 1584:1588 arg1 composition 1590:1600 sialylated mucin composition 1573:1600 sialylated mucin composition 1573:1600 Our results indicate that specific alterations in sialylated mucin composition may be related to impaired cervical sperm transport. 35470857 3 68 from Belclare 565:572 arg1 Ireland 596:602 Ireland 596:602 Ireland 596:602 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 3 68 from Belclare 565:572 arg1 Norway 741:746 Norway 741:746 Norway 741:746 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 3 68 from Belclare 565:572 arg1 NWS 698:700 NWS 698:700 NWS 698:700 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 8 69 theme MUC5AC 1369:1374 arg1 expression 1355:1364 higher expression 1348:1364 higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 1348:1403 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 8 69 theme MUC5AC 1369:1374 arg1 expression 1415:1424 lower expression 1409:1424 lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 1409:1458 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 6 70 theme sialic 1113:1118 arg1 species 1125:1131 sialic acid species 1113:1131 sialic acid species 1113:1131 Biochemical analysis showed that there was an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05). 35470857 5 71 theme mucin 986:990 arg1 cells 1009:1013 mucin secreting goblet cells 986:1013 mucin secreting goblet cells in the same four ewe breeds 986:1041 Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. 35470857 3 72 theme Ile 605:607 arg1 France 612:617 Ile de France 605:617 Ile de France 605:617 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 1 73 theme mucins 149:154 arg1 O-glycans 127:135 O-glycans 127:135 O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport 127:248 Sialic acid occupies terminal positions on O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport. 35470857 0 74 from characterization 26:41 arg1 sheep† 76:81 sheep† 76:81 sheep† 76:81 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 35470857 6 75 theme breed 1104:1108 arg1 effect 1090:1095 an effect 1087:1095 an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05) 1087:1228 Biochemical analysis showed that there was an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05). 35470857 3 76 with France 612:617 arg1 fertility 649:657 medium fertility 642:657 medium fertility 642:657 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 9 77 from alterations 1558:1568 arg1 composition 1590:1600 sialylated mucin composition 1573:1600 sialylated mucin composition 1573:1600 Our results indicate that specific alterations in sialylated mucin composition may be related to impaired cervical sperm transport. 35470857 2 78 theme natural 503:509 arg1 cycles 518:523 both synchronized and natural estrus cycles 481:523 cycles 518:523 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 8 79 theme ST6GAL1 1384:1390 arg1 expression 1355:1364 higher expression 1348:1364 higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 1348:1403 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 8 79 theme ST6GAL1 1384:1390 arg1 expression 1415:1424 lower expression 1409:1424 lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 1409:1458 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 5 80 from cells 1009:1013 arg1 breeds 1036:1041 the same four ewe breeds 1018:1041 the same four ewe breeds 1018:1041 Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. 35470857 2 81 from mucus 329:333 arg1 mucins 300:305 the sialylated cervical mucins 276:305 the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates 276:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 9 82 theme sperm 1638:1642 arg1 transport 1644:1652 impaired cervical sperm transport 1620:1652 impaired cervical sperm transport 1620:1652 Our results indicate that specific alterations in sialylated mucin composition may be related to impaired cervical sperm transport. 35470857 0 83 from mucins 66:71 arg1 sheep† 76:81 sheep† 76:81 sheep† 76:81 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 35470857 6 84 from effect 1090:1095 arg1 species 1125:1131 sialic acid species 1113:1131 sialic acid species 1113:1131 Biochemical analysis showed that there was an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05). 35470857 5 85 theme same 1022:1025 arg1 breeds 1036:1041 the same four ewe breeds 1018:1041 the same four ewe breeds 1018:1041 Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. 35470857 5 86 theme Cervical 897:904 arg1 tissue 906:911 Cervical tissue 897:911 Cervical tissue 897:911 Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. 35470857 3 87 from France 612:617 arg1 France 663:668 France 663:668 France 663:668 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 3 88 with Belclare 565:572 arg1 fertility 727:735 high fertility 722:735 high fertility 722:735 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 5 89 theme ewe 1032:1034 arg1 breeds 1036:1041 the same four ewe breeds 1018:1041 the same four ewe breeds 1018:1041 Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. 35470857 2 90 theme frozen-thawed 458:470 arg1 semen 472:476 frozen-thawed semen 458:476 frozen-thawed semen 458:476 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 2 91 theme pregnancy 388:396 arg1 rates 398:402 pregnancy rates 388:402 pregnancy rates 388:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 1 92 theme terminal 105:112 arg1 positions 114:122 terminal positions 105:122 terminal positions 105:122 Sialic acid occupies terminal positions on O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport. 35470857 8 93 theme ST3GAL3 1429:1435 arg1 expression 1355:1364 higher expression 1348:1364 higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 1348:1403 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 8 93 theme ST3GAL3 1429:1435 arg1 expression 1415:1424 lower expression 1409:1424 lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 1409:1458 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 0 94 theme sialylated 46:55 arg1 mucins 66:71 sialylated cervical mucins 46:71 sialylated cervical mucins in sheep† 46:81 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 35470857 8 95 theme ST3GAL4 1438:1444 arg1 expression 1355:1364 higher expression 1348:1364 higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 1348:1403 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 8 95 theme ST3GAL4 1438:1444 arg1 expression 1415:1424 lower expression 1409:1424 lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 1409:1458 Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). 35470857 2 96 theme artificial 423:432 arg1 insemination 434:445 cervical artificial insemination 414:445 cervical artificial insemination (AI) 414:450 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 2 96 theme artificial 423:432 arg1 AI 448:449 AI 448:449 AI 448:449 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 0 97 theme mucins 66:71 arg1 characterization 26:41 Biochemical and molecular characterization 0:41 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 0:82 Biochemical and molecular characterization of sialylated cervical mucins in sheep†. 35470857 4 98 theme mucin 763:767 arg1 Expression 749:758 Expression 749:758 Expression of mucin and sialic acid related genes 749:797 Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. 35470857 2 99 theme ewe 351:353 arg1 breeds 355:360 six European ewe breeds 338:360 six European ewe breeds with known differences in pregnancy rates 338:402 This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. 35470857 3 100 theme medium 642:647 arg1 fertility 649:657 medium fertility 642:657 medium fertility 642:657 These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. 35470857 1 101 theme sperm 234:238 arg1 transport 240:248 sperm transport 234:248 sperm transport 234:248 Sialic acid occupies terminal positions on O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport. 35080445 4 0 theme spectrometry 603:614 arg1 analysis 624:631 Liquid chromatography-mass spectrometry (LC-MS) analysis 576:631 Liquid chromatography-mass spectrometry (LC-MS) analysis 576:631 Liquid chromatography-mass spectrometry (LC-MS) analysis indicated that OMVs carry sphingolipids, glycerophospholipids, and serine-dipeptide lipids. 35080445 13 1 theme other 1872:1876 arg1 lipids 1878:1883 other lipids 1872:1883 other lipids 1872:1883 Here, we determined that OMVs carry sphingolipids and other lipids of known signaling function. 35080445 11 2 theme signaling 1681:1689 arg1 processes 1691:1699 cell signaling processes 1676:1699 cell signaling processes 1676:1699 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 12 3 theme commensals 1806:1815 arg1 members 1759:1765 members 1759:1765 members of the phylum Bacteroidetes, human gut commensals 1759:1815 Although rare in bacteria, sphingolipids are produced by members of the phylum Bacteroidetes, human gut commensals. 35080445 9 4 theme mutant 1226:1231 arg1 strains 1233:1239 BT1522-1526 mutant strains 1214:1239 BT1522-1526 mutant strains lacking IPC 1214:1251 BT1522-1526 mutant strains lacking IPC produced OMVs that were indistinguishable from the wild-type strain, indicating that IPC sphingolipid species are not involved in OMV biogenesis. 35080445 3 5 theme Bacteroides 537:547 arg1 thetaiotaomicron 549:564 Bacteroides thetaiotaomicron VPI-5482 537:573 Bacteroides thetaiotaomicron VPI-5482 537:573 In this work, we characterize the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482. 35080445 8 6 theme IPC 1209:1211 arg1 biosynthesis 1193:1204 the biosynthesis 1189:1204 the biosynthesis of IPC 1189:1211 Mutagenesis studies revealed that BT1522-1526 is essential for the synthesis of phosphatidylinositol (PI) and IPC, confirming the role of this operon in the biosynthesis of IPC. 35080445 12 7 dep phylum 1774:1779 arg1 Bacteroidetes 1781:1793 Bacteroidetes 1781:1793 Bacteroidetes 1781:1793 Although rare in bacteria, sphingolipids are produced by members of the phylum Bacteroidetes, human gut commensals. 35080445 3 8 theme OMVs 527:530 arg1 composition 498:508 the lipid composition 488:508 the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482 488:573 In this work, we characterize the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482. 35080445 4 9 theme serine-dipeptide 700:715 arg1 lipids 717:722 serine-dipeptide lipids 700:722 serine-dipeptide lipids 700:722 Liquid chromatography-mass spectrometry (LC-MS) analysis indicated that OMVs carry sphingolipids, glycerophospholipids, and serine-dipeptide lipids. 35080445 11 10 located found 1630:1634 arg2 components 1619:1628 essential membrane lipid components 1594:1628 essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes 1594:1699 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 11 10 located found 1630:1634 arg1 eukaryotes 1639:1648 eukaryotes 1639:1648 eukaryotes that are also involved in cell signaling processes 1639:1699 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 11 10 located found 1630:1634 arg2 Sphingolipids 1576:1588 IMPORTANCE Sphingolipids 1565:1588 IMPORTANCE Sphingolipids 1565:1588 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 11 11 theme membrane 1604:1611 arg1 components 1619:1628 essential membrane lipid components 1594:1628 essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes 1594:1699 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 11 11 theme membrane 1604:1611 arg1 Sphingolipids 1576:1588 IMPORTANCE Sphingolipids 1565:1588 IMPORTANCE Sphingolipids 1565:1588 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 12 12 theme human 1796:1800 arg1 commensals 1806:1815 the phylum Bacteroidetes, human gut commensals 1770:1815 commensals 1806:1815 Although rare in bacteria, sphingolipids are produced by members of the phylum Bacteroidetes, human gut commensals. 35080445 2 13 theme membrane 318:325 arg1 vesicles 327:334 outer membrane vesicles 312:334 uniformly sized outer membrane vesicles (OMVs) 296:341 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 2 13 theme membrane 318:325 arg1 OMVs 337:340 OMVs 337:340 OMVs 337:340 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 1 14 theme genus 236:240 arg1 Bacteroides 242:252 the genus Bacteroides 232:252 the genus Bacteroides 232:252 Approximately one-third of the human colonic microbiome is formed by bacteria from the genus Bacteroides. 35080445 1 15 from Bacteroides 242:252 arg1 bacteria 218:225 bacteria 218:225 bacteria from the genus Bacteroides 218:252 Approximately one-third of the human colonic microbiome is formed by bacteria from the genus Bacteroides. 35080445 11 16 theme essential 1594:1602 arg1 components 1619:1628 essential membrane lipid components 1594:1628 essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes 1594:1699 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 11 16 theme essential 1594:1602 arg1 Sphingolipids 1576:1588 IMPORTANCE Sphingolipids 1565:1588 IMPORTANCE Sphingolipids 1565:1588 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 2 17 theme large 280:284 arg1 vesicles 327:334 outer membrane vesicles 312:334 uniformly sized outer membrane vesicles (OMVs) 296:341 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 2 17 theme large 280:284 arg1 OMVs 337:340 OMVs 337:340 OMVs 337:340 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 2 17 theme large 280:284 arg1 amount 286:291 a large amount 278:291 a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans 278:455 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 14 18 from biosynthesis 1986:1997 arg1 thetaiotaomicron 2005:2020 B. thetaiotaomicron 2002:2020 B. thetaiotaomicron 2002:2020 Our results demonstrate that the BT1522-1526 operon is required for IPC biosynthesis in B. thetaiotaomicron. 35080445 12 19 theme phylum 1774:1779 arg1 commensals 1806:1815 the phylum Bacteroidetes, human gut commensals 1770:1815 commensals 1806:1815 Although rare in bacteria, sphingolipids are produced by members of the phylum Bacteroidetes, human gut commensals. 35080445 10 20 from delivery 1521:1528 arg1 gut 1560:1562 the human gut 1550:1562 the human gut 1550:1562 Given the known role of sphingolipids in immunomodulation, we suggest that OMVs may act as long-distance vehicles for the delivery of sphingolipids in the human gut. 35080445 5 21 theme content 789:795 arg1 content 789:795 the total lipid content 773:795 the total lipid content of OMVs 773:803 Sphingolipid species represent more than 50% of the total lipid content of OMVs. 35080445 5 21 theme content 789:795 arg1 % 768:768 more than 50% 756:768 more than 50% of the total lipid content of OMVs 756:803 Sphingolipid species represent more than 50% of the total lipid content of OMVs. 35080445 7 22 theme IPC 1021:1023 arg1 synthesis 1025:1033 IPC synthesis 1021:1033 IPC synthesis 1021:1033 Bioinformatics analysis allowed the identification of the BT1522-1526 operon putatively involved in IPC synthesis. 35080445 0 23 theme Inositol 70:77 arg1 Pathway 108:114 the Inositol Phosphoceramide Biosynthetic Pathway 66:114 the Inositol Phosphoceramide Biosynthetic Pathway 66:114 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 9 24 theme IPC 1338:1340 arg1 species 1355:1361 IPC sphingolipid species 1338:1361 IPC sphingolipid species 1338:1361 BT1522-1526 mutant strains lacking IPC produced OMVs that were indistinguishable from the wild-type strain, indicating that IPC sphingolipid species are not involved in OMV biogenesis. 35080445 1 25 theme colonic 186:192 arg1 microbiome 194:203 the human colonic microbiome 176:203 the human colonic microbiome 176:203 Approximately one-third of the human colonic microbiome is formed by bacteria from the genus Bacteroides. 35080445 0 26 from Lipidomics 0:9 arg1 thetaiotaomicron 131:146 Bacteroides thetaiotaomicron 119:146 Bacteroides thetaiotaomicron 119:146 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 11 27 theme IMPORTANCE 1565:1574 arg1 components 1619:1628 essential membrane lipid components 1594:1628 essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes 1594:1699 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 11 27 theme IMPORTANCE 1565:1574 arg1 Sphingolipids 1576:1588 IMPORTANCE Sphingolipids 1565:1588 IMPORTANCE Sphingolipids 1565:1588 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 0 28 theme Biosynthetic 95:106 arg1 Pathway 108:114 the Inositol Phosphoceramide Biosynthetic Pathway 66:114 the Inositol Phosphoceramide Biosynthetic Pathway 66:114 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 2 29 theme sized 306:310 arg1 vesicles 327:334 outer membrane vesicles 312:334 uniformly sized outer membrane vesicles (OMVs) 296:341 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 2 29 theme sized 306:310 arg1 OMVs 337:340 OMVs 337:340 OMVs 337:340 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 7 30 theme operon 991:996 arg1 identification 957:970 the identification 953:970 the identification of the BT1522-1526 operon putatively involved in IPC synthesis 953:1033 Bioinformatics analysis allowed the identification of the BT1522-1526 operon putatively involved in IPC synthesis. 35080445 2 31 link host-derived 436:447 arg1 glycans 449:455 diet- and host-derived glycans 426:455 diet- and host-derived glycans 426:455 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 5 32 theme total 777:781 arg1 content 789:795 the total lipid content 773:795 the total lipid content of OMVs 773:803 Sphingolipid species represent more than 50% of the total lipid content of OMVs. 35080445 6 33 from sphingolipids 824:836 arg1 OMVs 841:844 OMVs 841:844 OMVs 841:844 The most abundant sphingolipids in OMVs are ethanolamine phosphoceramide (EPC) and inositol phosphoceramide (IPC). 35080445 2 34 theme glycans 449:455 arg1 degradation 411:421 the degradation 407:421 the degradation of diet- and host-derived glycans 407:455 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 8 35 theme phosphatidylinositol 1116:1135 arg1 synthesis 1103:1111 the synthesis 1099:1111 the synthesis of phosphatidylinositol (PI) and IPC 1099:1148 Mutagenesis studies revealed that BT1522-1526 is essential for the synthesis of phosphatidylinositol (PI) and IPC, confirming the role of this operon in the biosynthesis of IPC. 35080445 13 36 theme signaling 1894:1902 arg1 function 1904:1911 known signaling function 1888:1911 known signaling function 1888:1911 Here, we determined that OMVs carry sphingolipids and other lipids of known signaling function. 35080445 0 37 theme Membrane 29:36 arg1 Vesicles 38:45 Outer Membrane Vesicles 23:45 Outer Membrane Vesicles 23:45 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 4 38 contain carry 653:657 arg2 lipids 717:722 serine-dipeptide lipids 700:722 serine-dipeptide lipids 700:722 Liquid chromatography-mass spectrometry (LC-MS) analysis indicated that OMVs carry sphingolipids, glycerophospholipids, and serine-dipeptide lipids. 35080445 4 38 contain carry 653:657 arg1 OMVs 648:651 OMVs 648:651 OMVs 648:651 Liquid chromatography-mass spectrometry (LC-MS) analysis indicated that OMVs carry sphingolipids, glycerophospholipids, and serine-dipeptide lipids. 35080445 4 38 contain carry 653:657 arg2 glycerophospholipids 674:693 glycerophospholipids 674:693 glycerophospholipids 674:693 Liquid chromatography-mass spectrometry (LC-MS) analysis indicated that OMVs carry sphingolipids, glycerophospholipids, and serine-dipeptide lipids. 35080445 4 38 contain carry 653:657 arg2 sphingolipids 659:671 sphingolipids 659:671 sphingolipids 659:671 Liquid chromatography-mass spectrometry (LC-MS) analysis indicated that OMVs carry sphingolipids, glycerophospholipids, and serine-dipeptide lipids. 35080445 10 39 theme human 1554:1558 arg1 gut 1560:1562 the human gut 1550:1562 the human gut 1550:1562 Given the known role of sphingolipids in immunomodulation, we suggest that OMVs may act as long-distance vehicles for the delivery of sphingolipids in the human gut. 35080445 6 40 theme abundant 815:822 arg1 phosphoceramide 863:877 ethanolamine phosphoceramide 850:877 ethanolamine phosphoceramide (EPC) 850:883 The most abundant sphingolipids in OMVs are ethanolamine phosphoceramide (EPC) and inositol phosphoceramide (IPC). 35080445 6 40 theme abundant 815:822 arg1 sphingolipids 824:836 The most abundant sphingolipids 806:836 The most abundant sphingolipids in OMVs 806:844 The most abundant sphingolipids in OMVs are ethanolamine phosphoceramide (EPC) and inositol phosphoceramide (IPC). 35080445 10 41 theme known 1409:1413 arg1 role 1415:1418 the known role 1405:1418 the known role of sphingolipids in immunomodulation 1405:1455 Given the known role of sphingolipids in immunomodulation, we suggest that OMVs may act as long-distance vehicles for the delivery of sphingolipids in the human gut. 35080445 14 42 theme IPC 1982:1984 arg1 biosynthesis 1986:1997 IPC biosynthesis 1982:1997 IPC biosynthesis in B. thetaiotaomicron 1982:2020 Our results demonstrate that the BT1522-1526 operon is required for IPC biosynthesis in B. thetaiotaomicron. 35080445 3 43 theme lipid 492:496 arg1 composition 498:508 the lipid composition 488:508 the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482 488:573 In this work, we characterize the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482. 35080445 8 44 theme operon 1179:1184 arg1 role 1166:1169 the role 1162:1169 the role of this operon in the biosynthesis of IPC 1162:1211 Mutagenesis studies revealed that BT1522-1526 is essential for the synthesis of phosphatidylinositol (PI) and IPC, confirming the role of this operon in the biosynthesis of IPC. 35080445 4 45 theme chromatography-mass 583:601 arg1 LC-MS 617:621 LC-MS 617:621 LC-MS 617:621 Liquid chromatography-mass spectrometry (LC-MS) analysis indicated that OMVs carry sphingolipids, glycerophospholipids, and serine-dipeptide lipids. 35080445 4 45 theme chromatography-mass 583:601 arg1 spectrometry 603:614 Liquid chromatography-mass spectrometry 576:614 Liquid chromatography-mass spectrometry (LC-MS) analysis 576:631 Liquid chromatography-mass spectrometry (LC-MS) analysis indicated that OMVs carry sphingolipids, glycerophospholipids, and serine-dipeptide lipids. 35080445 3 46 from composition 498:508 arg1 thetaiotaomicron 549:564 Bacteroides thetaiotaomicron VPI-5482 537:573 Bacteroides thetaiotaomicron VPI-5482 537:573 In this work, we characterize the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482. 35080445 2 47 theme outer 312:316 arg1 vesicles 327:334 outer membrane vesicles 312:334 uniformly sized outer membrane vesicles (OMVs) 296:341 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 2 47 theme outer 312:316 arg1 OMVs 337:340 OMVs 337:340 OMVs 337:340 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 8 48 theme Mutagenesis 1036:1046 arg1 studies 1048:1054 Mutagenesis studies 1036:1054 Mutagenesis studies 1036:1054 Mutagenesis studies revealed that BT1522-1526 is essential for the synthesis of phosphatidylinositol (PI) and IPC, confirming the role of this operon in the biosynthesis of IPC. 35080445 12 49 from bacteria 1719:1726 arg1 rare 1711:1714 rare 1711:1714 rare 1711:1714 Although rare in bacteria, sphingolipids are produced by members of the phylum Bacteroidetes, human gut commensals. 35080445 1 50 theme microbiome 194:203 arg1 microbiome 194:203 the human colonic microbiome 176:203 the human colonic microbiome 176:203 Approximately one-third of the human colonic microbiome is formed by bacteria from the genus Bacteroides. 35080445 1 50 theme microbiome 194:203 arg1 one-third 163:171 one-third 163:171 one-third 163:171 Approximately one-third of the human colonic microbiome is formed by bacteria from the genus Bacteroides. 35080445 12 51 from rare 1711:1714 arg1 bacteria 1719:1726 bacteria 1719:1726 bacteria 1719:1726 Although rare in bacteria, sphingolipids are produced by members of the phylum Bacteroidetes, human gut commensals. 35080445 5 52 theme OMVs 800:803 arg1 content 789:795 the total lipid content 773:795 the total lipid content of OMVs 773:803 Sphingolipid species represent more than 50% of the total lipid content of OMVs. 35080445 12 53 theme gut 1802:1804 arg1 commensals 1806:1815 the phylum Bacteroidetes, human gut commensals 1770:1815 commensals 1806:1815 Although rare in bacteria, sphingolipids are produced by members of the phylum Bacteroidetes, human gut commensals. 35080445 11 54 theme lipid 1613:1617 arg1 components 1619:1628 essential membrane lipid components 1594:1628 essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes 1594:1699 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 11 54 theme lipid 1613:1617 arg1 Sphingolipids 1576:1588 IMPORTANCE Sphingolipids 1565:1588 IMPORTANCE Sphingolipids 1565:1588 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 2 55 theme vesicles 327:334 arg1 vesicles 327:334 outer membrane vesicles 312:334 uniformly sized outer membrane vesicles (OMVs) 296:341 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 2 55 theme vesicles 327:334 arg1 OMVs 337:340 OMVs 337:340 OMVs 337:340 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 2 55 theme vesicles 327:334 arg1 amount 286:291 a large amount 278:291 a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans 278:455 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 3 56 from thetaiotaomicron 549:564 arg1 composition 498:508 the lipid composition 488:508 the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482 488:573 In this work, we characterize the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482. 35080445 3 56 from thetaiotaomicron 549:564 arg1 OMVs 527:530 OMVs 527:530 OMVs 527:530 In this work, we characterize the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482. 35080445 3 56 from thetaiotaomicron 549:564 arg1 membranes 513:521 membranes 513:521 membranes 513:521 In this work, we characterize the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482. 35080445 5 57 theme Sphingolipid 725:736 arg1 species 738:744 Sphingolipid species 725:744 Sphingolipid species 725:744 Sphingolipid species represent more than 50% of the total lipid content of OMVs. 35080445 9 58 theme wild-type 1304:1312 arg1 strain 1314:1319 the wild-type strain 1300:1319 the wild-type strain 1300:1319 BT1522-1526 mutant strains lacking IPC produced OMVs that were indistinguishable from the wild-type strain, indicating that IPC sphingolipid species are not involved in OMV biogenesis. 35080445 5 59 theme lipid 783:787 arg1 content 789:795 the total lipid content 773:795 the total lipid content of OMVs 773:803 Sphingolipid species represent more than 50% of the total lipid content of OMVs. 35080445 0 60 theme Phosphoceramide 79:93 arg1 Pathway 108:114 the Inositol Phosphoceramide Biosynthetic Pathway 66:114 the Inositol Phosphoceramide Biosynthetic Pathway 66:114 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 1 61 theme human 180:184 arg1 microbiome 194:203 the human colonic microbiome 176:203 the human colonic microbiome 176:203 Approximately one-third of the human colonic microbiome is formed by bacteria from the genus Bacteroides. 35080445 8 62 from role 1166:1169 arg1 biosynthesis 1193:1204 the biosynthesis 1189:1204 the biosynthesis of IPC 1189:1211 Mutagenesis studies revealed that BT1522-1526 is essential for the synthesis of phosphatidylinositol (PI) and IPC, confirming the role of this operon in the biosynthesis of IPC. 35080445 0 63 theme Pathway 108:114 arg1 Analysis 11:18 Analysis 11:18 Analysis of Outer Membrane Vesicles 11:45 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 0 63 theme Pathway 108:114 arg1 Elucidation 51:61 Elucidation 51:61 Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway 51:114 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 9 64 theme sphingolipid 1342:1353 arg1 species 1355:1361 IPC sphingolipid species 1338:1361 IPC sphingolipid species 1338:1361 BT1522-1526 mutant strains lacking IPC produced OMVs that were indistinguishable from the wild-type strain, indicating that IPC sphingolipid species are not involved in OMV biogenesis. 35080445 13 65 theme function 1904:1911 arg1 sphingolipids 1854:1866 sphingolipids 1854:1866 sphingolipids 1854:1866 Here, we determined that OMVs carry sphingolipids and other lipids of known signaling function. 35080445 13 65 theme function 1904:1911 arg1 lipids 1878:1883 other lipids 1872:1883 other lipids 1872:1883 Here, we determined that OMVs carry sphingolipids and other lipids of known signaling function. 35080445 0 66 theme Bacteroides 119:129 arg1 thetaiotaomicron 131:146 Bacteroides thetaiotaomicron 119:146 Bacteroides thetaiotaomicron 119:146 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 7 67 theme BT1522-1526 979:989 arg1 operon 991:996 the BT1522-1526 operon 975:996 the BT1522-1526 operon putatively involved in IPC synthesis 975:1033 Bioinformatics analysis allowed the identification of the BT1522-1526 operon putatively involved in IPC synthesis. 35080445 2 68 theme host-derived 436:447 arg1 glycans 449:455 diet- and host-derived glycans 426:455 diet- and host-derived glycans 426:455 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 10 69 theme long-distance 1490:1502 arg1 vehicles 1504:1511 long-distance vehicles 1490:1511 long-distance vehicles for the delivery of sphingolipids in the human gut 1490:1562 Given the known role of sphingolipids in immunomodulation, we suggest that OMVs may act as long-distance vehicles for the delivery of sphingolipids in the human gut. 35080445 10 69 theme long-distance 1490:1502 arg1 OMVs 1474:1477 OMVs 1474:1477 OMVs 1474:1477 Given the known role of sphingolipids in immunomodulation, we suggest that OMVs may act as long-distance vehicles for the delivery of sphingolipids in the human gut. 35080445 0 70 theme Outer 23:27 arg1 Vesicles 38:45 Outer Membrane Vesicles 23:45 Outer Membrane Vesicles 23:45 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 9 71 theme OMV 1383:1385 arg1 biogenesis 1387:1396 OMV biogenesis 1383:1396 OMV biogenesis 1383:1396 BT1522-1526 mutant strains lacking IPC produced OMVs that were indistinguishable from the wild-type strain, indicating that IPC sphingolipid species are not involved in OMV biogenesis. 35080445 2 72 theme diet- 426:430 arg1 glycans 449:455 diet- and host-derived glycans 426:455 diet- and host-derived glycans 426:455 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 4 73 theme Liquid 576:581 arg1 LC-MS 617:621 LC-MS 617:621 LC-MS 617:621 Liquid chromatography-mass spectrometry (LC-MS) analysis indicated that OMVs carry sphingolipids, glycerophospholipids, and serine-dipeptide lipids. 35080445 4 73 theme Liquid 576:581 arg1 spectrometry 603:614 Liquid chromatography-mass spectrometry 576:614 Liquid chromatography-mass spectrometry (LC-MS) analysis 576:631 Liquid chromatography-mass spectrometry (LC-MS) analysis indicated that OMVs carry sphingolipids, glycerophospholipids, and serine-dipeptide lipids. 35080445 10 74 theme sphingolipids 1533:1545 arg1 delivery 1521:1528 the delivery 1517:1528 the delivery of sphingolipids in the human gut 1517:1562 Given the known role of sphingolipids in immunomodulation, we suggest that OMVs may act as long-distance vehicles for the delivery of sphingolipids in the human gut. 35080445 13 75 theme known 1888:1892 arg1 function 1904:1911 known signaling function 1888:1911 known signaling function 1888:1911 Here, we determined that OMVs carry sphingolipids and other lipids of known signaling function. 35080445 0 76 theme Vesicles 38:45 arg1 Analysis 11:18 Analysis 11:18 Analysis of Outer Membrane Vesicles 11:45 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 0 76 theme Vesicles 38:45 arg1 Elucidation 51:61 Elucidation 51:61 Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway 51:114 Lipidomics Analysis of Outer Membrane Vesicles and Elucidation of the Inositol Phosphoceramide Biosynthetic Pathway in Bacteroides thetaiotaomicron. 35080445 8 77 theme IPC 1146:1148 arg1 synthesis 1103:1111 the synthesis 1099:1111 the synthesis of phosphatidylinositol (PI) and IPC 1099:1148 Mutagenesis studies revealed that BT1522-1526 is essential for the synthesis of phosphatidylinositol (PI) and IPC, confirming the role of this operon in the biosynthesis of IPC. 35080445 6 78 theme inositol 889:896 arg1 IPC 915:917 IPC 915:917 IPC 915:917 The most abundant sphingolipids in OMVs are ethanolamine phosphoceramide (EPC) and inositol phosphoceramide (IPC). 35080445 6 78 theme inositol 889:896 arg1 phosphoceramide 898:912 inositol phosphoceramide 889:912 inositol phosphoceramide (IPC) 889:918 The most abundant sphingolipids in OMVs are ethanolamine phosphoceramide (EPC) and inositol phosphoceramide (IPC). 35080445 10 79 from role 1415:1418 arg1 immunomodulation 1440:1455 immunomodulation 1440:1455 immunomodulation 1440:1455 Given the known role of sphingolipids in immunomodulation, we suggest that OMVs may act as long-distance vehicles for the delivery of sphingolipids in the human gut. 35080445 13 80 contain carry 1848:1852 arg2 lipids 1878:1883 other lipids 1872:1883 other lipids 1872:1883 Here, we determined that OMVs carry sphingolipids and other lipids of known signaling function. 35080445 13 80 contain carry 1848:1852 arg2 sphingolipids 1854:1866 sphingolipids 1854:1866 sphingolipids 1854:1866 Here, we determined that OMVs carry sphingolipids and other lipids of known signaling function. 35080445 13 80 contain carry 1848:1852 arg1 OMVs 1843:1846 OMVs 1843:1846 OMVs 1843:1846 Here, we determined that OMVs carry sphingolipids and other lipids of known signaling function. 35080445 11 81 theme cell 1676:1679 arg1 processes 1691:1699 cell signaling processes 1676:1699 cell signaling processes 1676:1699 IMPORTANCE Sphingolipids are essential membrane lipid components found in eukaryotes that are also involved in cell signaling processes. 35080445 14 82 theme B. 2002:2003 arg1 thetaiotaomicron 2005:2020 B. thetaiotaomicron 2002:2020 B. thetaiotaomicron 2002:2020 Our results demonstrate that the BT1522-1526 operon is required for IPC biosynthesis in B. thetaiotaomicron. 35080445 2 83 theme hydrolytic 368:377 arg1 enzymes 379:385 hydrolytic enzymes 368:385 hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans 368:455 These bacteria produce a large amount of uniformly sized outer membrane vesicles (OMVs), which are equipped with hydrolytic enzymes that play a role in the degradation of diet- and host-derived glycans. 35080445 7 84 theme Bioinformatics 921:934 arg1 analysis 936:943 Bioinformatics analysis 921:943 Bioinformatics analysis 921:943 Bioinformatics analysis allowed the identification of the BT1522-1526 operon putatively involved in IPC synthesis. 35080445 9 85 from strain 1314:1319 arg1 indistinguishable 1277:1293 indistinguishable 1277:1293 indistinguishable 1277:1293 BT1522-1526 mutant strains lacking IPC produced OMVs that were indistinguishable from the wild-type strain, indicating that IPC sphingolipid species are not involved in OMV biogenesis. 35080445 6 86 theme ethanolamine 850:861 arg1 EPC 880:882 EPC 880:882 EPC 880:882 The most abundant sphingolipids in OMVs are ethanolamine phosphoceramide (EPC) and inositol phosphoceramide (IPC). 35080445 6 86 theme ethanolamine 850:861 arg1 phosphoceramide 863:877 ethanolamine phosphoceramide 850:877 ethanolamine phosphoceramide (EPC) 850:883 The most abundant sphingolipids in OMVs are ethanolamine phosphoceramide (EPC) and inositol phosphoceramide (IPC). 35080445 6 86 theme ethanolamine 850:861 arg1 sphingolipids 824:836 The most abundant sphingolipids 806:836 The most abundant sphingolipids in OMVs 806:844 The most abundant sphingolipids in OMVs are ethanolamine phosphoceramide (EPC) and inositol phosphoceramide (IPC). 35080445 10 87 theme sphingolipids 1423:1435 arg1 role 1415:1418 the known role 1405:1418 the known role of sphingolipids in immunomodulation 1405:1455 Given the known role of sphingolipids in immunomodulation, we suggest that OMVs may act as long-distance vehicles for the delivery of sphingolipids in the human gut. 35080445 3 88 theme membranes 513:521 arg1 composition 498:508 the lipid composition 488:508 the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482 488:573 In this work, we characterize the lipid composition of membranes and OMVs from Bacteroides thetaiotaomicron VPI-5482. 37233225 0 0 theme Cassava 82:88 arg1 Stress 96:101 Cassava Stalk Stress 82:101 Cassava Stalk Stress 82:101 Study on the Structure and Bioactivity of Ganoderma lucidum Polysaccharides under Cassava Stalk Stress. 37233225 2 1 theme cassava 450:456 arg1 stress 464:469 cassava stalk stress 450:469 cassava stalk stress 450:469 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 5 2 dep highest 788:794 arg1 % 801:801 4.07% 797:801 4.07% 797:801 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 9 3 theme essential 1297:1305 arg1 source 1350:1355 a carbon source 1341:1355 a carbon source 1341:1355 This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation. 37233225 9 3 theme essential 1297:1305 arg1 support 1312:1318 essential data support 1297:1318 essential data support for cassava stalk 1297:1336 This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation. 37233225 2 4 theme antioxidant 338:348 arg1 activity 350:357 antioxidant activity 338:357 antioxidant activity in vitro 338:366 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 1 5 theme carbon 226:231 arg1 source 233:238 a promising carbon source 214:238 a promising carbon source for G. lucidum 214:253 Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. 37233225 5 6 theme total 752:756 arg1 highest 788:794 highest 788:794 highest 788:794 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 5 6 theme total 752:756 arg1 content 764:770 The total sugar content 748:770 The total sugar content in GLP1 748:778 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 1 7 theme G. 152:153 arg1 body 172:175 the G. lucidum fruiting body 148:175 the G. lucidum fruiting body 148:175 Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. 37233225 7 8 theme antioxidant 1023:1033 arg1 capacities 1035:1044 The total antioxidant capacities 1013:1044 The total antioxidant capacities of GLPs obtained from different cassava stalks 1013:1091 The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. 37233225 2 9 theme gas 492:494 arg1 spectrometry 516:527 gas chromatography-mass spectrometry 492:527 gas chromatography-mass spectrometry 492:527 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 5 10 from content 764:770 arg1 GLP1 775:778 GLP1 775:778 GLP1 775:778 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 6 11 dep greater 967:973 arg1 weight 997:1002 the maximum molecular weight 975:1002 the greater the maximum molecular weight of GLPs 963:1010 The greater the proportion of cassava stalk, the greater the maximum molecular weight of GLPs. 37233225 0 12 theme Stalk 90:94 arg1 Stress 96:101 Cassava Stalk Stress 82:101 Cassava Stalk Stress 82:101 Study on the Structure and Bioactivity of Ganoderma lucidum Polysaccharides under Cassava Stalk Stress. 37233225 7 13 theme total 1017:1021 arg1 capacities 1035:1044 The total antioxidant capacities 1013:1044 The total antioxidant capacities of GLPs obtained from different cassava stalks 1013:1091 The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. 37233225 5 14 theme β-D-Glc 895:901 arg1 configuration 903:915 the β-D-Glc configuration 891:915 the β-D-Glc configuration 891:915 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 1 15 theme G. 244:245 arg1 lucidum 247:253 G. lucidum 244:253 G. lucidum 244:253 Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. 37233225 6 16 dep greater 922:928 arg1 proportion 934:943 the proportion 930:943 The greater the proportion of cassava stalk 918:960 The greater the proportion of cassava stalk, the greater the maximum molecular weight of GLPs. 37233225 6 17 theme molecular 987:995 arg1 weight 997:1002 the maximum molecular weight 975:1002 the greater the maximum molecular weight of GLPs 963:1010 The greater the proportion of cassava stalk, the greater the maximum molecular weight of GLPs. 37233225 8 18 theme rhamnosus 1262:1270 arg1 LGG 1272:1274 L. rhamnosus LGG 1259:1274 L. rhamnosus LGG 1259:1274 Higher concentrations of GLPs corresponded to the more intensive growth of L. rhamnosus LGG. 37233225 5 19 contain had 887:889 arg1 GLP6 882:885 GLP6 882:885 GLP6 882:885 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 5 19 contain had 887:889 arg1 GLP4 873:876 GLP4 873:876 GLP4 873:876 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 5 19 contain had 887:889 arg2 configuration 903:915 the β-D-Glc configuration 891:915 the β-D-Glc configuration 891:915 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 1 20 theme lucidum 155:161 arg1 body 172:175 the G. lucidum fruiting body 148:175 the G. lucidum fruiting body 148:175 Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. 37233225 7 21 theme GLPs 1049:1052 arg1 capacities 1035:1044 The total antioxidant capacities 1013:1044 The total antioxidant capacities of GLPs obtained from different cassava stalks 1013:1091 The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. 37233225 8 22 theme L. 1259:1260 arg1 LGG 1272:1274 L. rhamnosus LGG 1259:1274 L. rhamnosus LGG 1259:1274 Higher concentrations of GLPs corresponded to the more intensive growth of L. rhamnosus LGG. 37233225 1 23 theme fruiting 163:170 arg1 body 172:175 the G. lucidum fruiting body 148:175 the G. lucidum fruiting body 148:175 Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. 37233225 2 24 theme lucidum 413:419 arg1 GLPs 438:441 GLPs 438:441 GLPs 438:441 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 2 24 theme lucidum 413:419 arg1 polysaccharides 421:435 G. lucidum polysaccharides 410:435 G. lucidum polysaccharides (GLPs) 410:442 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 7 25 theme stimulating 1132:1142 arg1 effects 1144:1150 their stimulating effects 1126:1150 their stimulating effects on the L. rhamnosus LGG growth 1126:1181 The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. 37233225 4 26 theme β-D-Glc 712:718 arg1 configurations 732:745 β-D-Glc and β-D-Gal configurations 712:745 β-D-Glc and β-D-Gal configurations 712:745 The end of the sugar chain had β-D-Glc and β-D-Gal configurations. 37233225 1 27 theme body 172:175 arg1 growth 138:143 the growth 134:143 the growth of the G. lucidum fruiting body 134:175 Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. 37233225 2 28 theme G. 410:411 arg1 lucidum 413:419 G. lucidum 410:419 G. lucidum polysaccharides (GLPs) 410:442 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 2 29 theme group 284:288 arg1 characteristics 290:304 functional group characteristics 273:304 functional group characteristics 273:304 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 7 30 theme different 1068:1076 arg1 stalks 1086:1091 different cassava stalks 1068:1091 different cassava stalks 1068:1091 The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. 37233225 2 31 theme near-infrared 530:542 arg1 spectroscopy 544:555 near-infrared spectroscopy 530:555 near-infrared spectroscopy 530:555 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 5 32 theme β-D-Gal 844:850 arg1 configuration 852:864 the β-D-Gal configuration 840:864 the β-D-Gal configuration 840:864 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 2 33 theme functional 273:282 arg1 characteristics 290:304 functional group characteristics 273:304 functional group characteristics 273:304 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 2 34 theme rhamnosus 393:401 arg1 LGG 403:405 L. rhamnosus LGG 390:405 L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress 390:469 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 2 35 theme LGG 403:405 arg1 distribution 324:335 molecular weight distribution 307:335 molecular weight distribution 307:335 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 2 35 theme LGG 403:405 arg1 composition 260:270 The composition 256:270 The composition 256:270 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 2 35 theme LGG 403:405 arg1 activity 350:357 antioxidant activity 338:357 antioxidant activity in vitro 338:366 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 2 35 theme LGG 403:405 arg1 effect 380:385 growth effect 373:385 growth effect 373:385 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 2 35 theme LGG 403:405 arg1 characteristics 290:304 functional group characteristics 273:304 functional group characteristics 273:304 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 4 36 contain had 708:710 arg1 end 685:687 The end 681:687 The end of the sugar chain 681:706 The end of the sugar chain had β-D-Glc and β-D-Gal configurations. 37233225 4 36 contain had 708:710 arg2 configurations 732:745 β-D-Glc and β-D-Gal configurations 712:745 β-D-Glc and β-D-Gal configurations 712:745 The end of the sugar chain had β-D-Glc and β-D-Gal configurations. 37233225 1 37 theme Various 104:110 arg1 sources 119:125 Various carbon sources 104:125 Various carbon sources 104:125 Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. 37233225 2 38 theme L. 390:391 arg1 LGG 403:405 L. rhamnosus LGG 390:405 L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress 390:469 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 5 39 theme sugar 758:762 arg1 highest 788:794 highest 788:794 highest 788:794 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 5 39 theme sugar 758:762 arg1 content 764:770 The total sugar content 748:770 The total sugar content in GLP1 748:778 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 8 40 theme Higher 1184:1189 arg1 concentrations 1191:1204 Higher concentrations 1184:1204 Higher concentrations of GLPs 1184:1212 Higher concentrations of GLPs corresponded to the more intensive growth of L. rhamnosus LGG. 37233225 1 41 theme cassava 186:192 arg1 stalk 194:198 the cassava stalk 182:198 the cassava stalk 182:198 Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. 37233225 2 42 theme growth 373:378 arg1 effect 380:385 growth effect 373:385 growth effect 373:385 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 2 43 theme chromatography-mass 496:514 arg1 spectrometry 516:527 gas chromatography-mass spectrometry 492:527 gas chromatography-mass spectrometry 492:527 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 8 44 theme GLPs 1209:1212 arg1 concentrations 1191:1204 Higher concentrations 1184:1204 Higher concentrations of GLPs 1184:1212 Higher concentrations of GLPs corresponded to the more intensive growth of L. rhamnosus LGG. 37233225 6 45 theme cassava 948:954 arg1 stalk 956:960 cassava stalk 948:960 cassava stalk 948:960 The greater the proportion of cassava stalk, the greater the maximum molecular weight of GLPs. 37233225 0 46 theme Ganoderma 42:50 arg1 lucidum 52:58 Ganoderma lucidum 42:58 Ganoderma lucidum Polysaccharides 42:74 Study on the Structure and Bioactivity of Ganoderma lucidum Polysaccharides under Cassava Stalk Stress. 37233225 9 47 theme carbon 1343:1348 arg1 source 1350:1355 a carbon source 1341:1355 a carbon source 1341:1355 This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation. 37233225 9 47 theme carbon 1343:1348 arg1 support 1312:1318 essential data support 1297:1318 essential data support for cassava stalk 1297:1336 This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation. 37233225 2 48 theme gel 562:564 arg1 chromatography 566:579 gel chromatography 562:579 gel chromatography 562:579 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 2 49 theme stalk 458:462 arg1 stress 464:469 cassava stalk stress 450:469 cassava stalk stress 450:469 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 8 50 theme LGG 1272:1274 arg1 growth 1249:1254 the more intensive growth 1230:1254 the more intensive growth of L. rhamnosus LGG 1230:1274 Higher concentrations of GLPs corresponded to the more intensive growth of L. rhamnosus LGG. 37233225 1 51 theme carbon 112:117 arg1 sources 119:125 Various carbon sources 104:125 Various carbon sources 104:125 Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. 37233225 2 52 theme polysaccharides 421:435 arg1 LGG 403:405 L. rhamnosus LGG 390:405 L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress 390:469 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 5 53 contain had 836:838 arg1 GLP1 809:812 GLP1 809:812 GLP1 809:812 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 5 53 contain had 836:838 arg1 GLP2 815:818 GLP2 815:818 GLP2 815:818 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 5 53 contain had 836:838 arg1 GLP3 821:824 GLP3 821:824 GLP3 821:824 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 5 53 contain had 836:838 arg1 GLP5 831:834 GLP5 831:834 GLP5 831:834 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 5 53 contain had 836:838 arg2 configuration 852:864 the β-D-Gal configuration 840:864 the β-D-Gal configuration 840:864 The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. 37233225 2 54 theme weight 317:322 arg1 distribution 324:335 molecular weight distribution 307:335 molecular weight distribution 307:335 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 3 55 theme other 658:662 arg1 monosaccharides 664:678 seven other monosaccharides 652:678 seven other monosaccharides 652:678 The results showed that GLPs consisted of D-glucose, D-galactose, and seven other monosaccharides. 37233225 0 56 dep Structure 13:21 arg1 the 9:11 the 9:11 the 9:11 Study on the Structure and Bioactivity of Ganoderma lucidum Polysaccharides under Cassava Stalk Stress. 37233225 2 57 theme molecular 307:315 arg1 distribution 324:335 molecular weight distribution 307:335 molecular weight distribution 307:335 The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. 37233225 4 58 theme β-D-Gal 724:730 arg1 configurations 732:745 β-D-Glc and β-D-Gal configurations 712:745 β-D-Glc and β-D-Gal configurations 712:745 The end of the sugar chain had β-D-Glc and β-D-Gal configurations. 37233225 9 59 theme lucidum 1363:1369 arg1 cultivation 1371:1381 G. lucidum cultivation 1360:1381 G. lucidum cultivation 1360:1381 This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation. 37233225 9 60 theme cassava 1324:1330 arg1 stalk 1332:1336 cassava stalk 1324:1336 cassava stalk 1324:1336 This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation. 37233225 4 61 theme sugar 696:700 arg1 chain 702:706 the sugar chain 692:706 the sugar chain 692:706 The end of the sugar chain had β-D-Glc and β-D-Gal configurations. 37233225 8 62 theme intensive 1239:1247 arg1 growth 1249:1254 the more intensive growth 1230:1254 the more intensive growth of L. rhamnosus LGG 1230:1274 Higher concentrations of GLPs corresponded to the more intensive growth of L. rhamnosus LGG. 37233225 4 63 theme chain 702:706 arg1 end 685:687 The end 681:687 The end of the sugar chain 681:706 The end of the sugar chain had β-D-Glc and β-D-Gal configurations. 37233225 0 64 theme Polysaccharides 60:74 arg1 Bioactivity 27:37 Bioactivity 27:37 Bioactivity 27:37 Study on the Structure and Bioactivity of Ganoderma lucidum Polysaccharides under Cassava Stalk Stress. 37233225 0 64 theme Polysaccharides 60:74 arg1 Structure 13:21 Structure 13:21 Structure 13:21 Study on the Structure and Bioactivity of Ganoderma lucidum Polysaccharides under Cassava Stalk Stress. 37233225 7 65 from effects 1144:1150 arg1 growth 1176:1181 the L. rhamnosus LGG growth 1155:1181 the L. rhamnosus LGG growth 1155:1181 The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. 37233225 9 66 theme G. 1360:1361 arg1 lucidum 1363:1369 G. lucidum 1360:1369 G. lucidum cultivation 1360:1381 This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation. 37233225 7 67 theme L. 1159:1160 arg1 growth 1176:1181 the L. rhamnosus LGG growth 1155:1181 the L. rhamnosus LGG growth 1155:1181 The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. 37233225 6 68 theme maximum 979:985 arg1 weight 997:1002 the maximum molecular weight 975:1002 the greater the maximum molecular weight of GLPs 963:1010 The greater the proportion of cassava stalk, the greater the maximum molecular weight of GLPs. 37233225 9 69 theme data 1307:1310 arg1 source 1350:1355 a carbon source 1341:1355 a carbon source 1341:1355 This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation. 37233225 9 69 theme data 1307:1310 arg1 support 1312:1318 essential data support 1297:1318 essential data support for cassava stalk 1297:1336 This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation. 37233225 0 70 theme lucidum 52:58 arg1 Polysaccharides 60:74 Ganoderma lucidum Polysaccharides 42:74 Ganoderma lucidum Polysaccharides 42:74 Study on the Structure and Bioactivity of Ganoderma lucidum Polysaccharides under Cassava Stalk Stress. 37233225 7 71 theme cassava 1078:1084 arg1 stalks 1086:1091 different cassava stalks 1068:1091 different cassava stalks 1068:1091 The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. 37233225 7 72 theme LGG 1172:1174 arg1 growth 1176:1181 the L. rhamnosus LGG growth 1155:1181 the L. rhamnosus LGG growth 1155:1181 The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. 37233225 7 73 theme rhamnosus 1162:1170 arg1 growth 1176:1181 the L. rhamnosus LGG growth 1155:1181 the L. rhamnosus LGG growth 1155:1181 The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. 37233225 1 74 theme promising 216:224 arg1 source 233:238 a promising carbon source 214:238 a promising carbon source for G. lucidum 214:253 Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. 36553765 2 0 theme ethanol 526:532 arg1 extraction 534:543 ethanol extraction 526:543 G. lucidum ethanol extraction (GLE) 515:549 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 0 theme ethanol 526:532 arg1 GLE 546:548 GLE 546:548 GLE 546:548 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 4 1 theme MPO 867:869 arg1 activities 881:890 COX-2, MPO, and iNOS activities 860:890 COX-2, MPO, and iNOS activities 860:890 COX-2, MPO, and iNOS activities and the inflammatory cytokines' expressions were determined to demonstrate the inhibition inflammation by GLE. 36553765 7 2 theme signaling 1445:1453 arg1 pathways 1455:1462 TRAF6/MyD88/NF-κB signaling pathways 1427:1462 TRAF6/MyD88/NF-κB signaling pathways 1427:1462 Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. 36553765 1 3 theme Gloeostereum 172:183 arg1 mushrooms 140:148 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum 125:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum 125:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 1 3 theme Gloeostereum 172:183 arg1 incarnatum 185:194 Gloeostereum incarnatum 172:194 Gloeostereum incarnatum 172:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 8 4 theme signaling 1724:1732 arg1 pathways 1734:1741 TRAF6/MyD88/NF-κB signaling pathways 1706:1741 TRAF6/MyD88/NF-κB signaling pathways 1706:1741 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 36553765 4 5 theme inflammatory 900:911 arg1 cytokines 913:921 the inflammatory cytokines 896:921 the inflammatory cytokines' expressions 896:934 COX-2, MPO, and iNOS activities and the inflammatory cytokines' expressions were determined to demonstrate the inhibition inflammation by GLE. 36553765 8 6 theme colitis 1521:1527 arg1 recovery 1529:1536 DSS-induced colitis recovery 1509:1536 DSS-induced colitis recovery 1509:1536 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 36553765 8 7 theme intestinal 1591:1600 arg1 barrier 1610:1616 the intestinal mucosal barrier 1587:1616 the intestinal mucosal barrier 1587:1616 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 36553765 8 8 theme DSS-induced 1509:1519 arg1 colitis 1521:1527 DSS-induced colitis 1509:1527 DSS-induced colitis recovery 1509:1536 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 36553765 6 9 theme Escherichia_Shigella 1261:1280 arg1 abundance 1215:1223 the abundance 1211:1223 the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella 1211:1280 Furthermore, GLE modulated the composition of gut microbiota disturbed by DSS, as it decreased the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella, and increased Turicibacter and Bifidobacterium. 36553765 3 10 dep loss 755:758 arg1 indices 827:833 indices 827:833 indices 827:833 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 1 11 dep mushrooms 140:148 arg1 mushrooms 140:148 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum 125:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum 125:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 1 11 dep mushrooms 140:148 arg1 lucidum 160:166 Ganoderma lucidum 150:166 Ganoderma lucidum 150:166 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 1 11 dep mushrooms 140:148 arg1 incarnatum 185:194 Gloeostereum incarnatum 172:194 Gloeostereum incarnatum 172:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 7 12 theme adherens 1388:1395 arg1 junction 1397:1404 adherens junction 1388:1404 adherens junction 1388:1404 Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. 36553765 3 13 theme disease 810:816 arg1 activity 818:825 decreased disease activity 800:825 decreased disease activity 800:825 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 2 14 dep G. 556:557 arg1 GIE 590:592 GIE 590:592 GIE 590:592 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 14 dep G. 556:557 arg1 extraction 578:587 ethanol extraction 570:587 G. incarnatum ethanol extraction (GIE) 556:593 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 14 dep G. 556:557 arg1 incarnatum 559:568 G. incarnatum ethanol extraction (GIE) 556:593 G. incarnatum ethanol extraction (GIE) 556:593 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 5 15 theme occluding 1071:1079 arg1 levels 1034:1039 the levels 1030:1039 the levels of MUC2, ZO-1, claudin-3, and occluding 1030:1079 Meanwhile, GLE upregulated the levels of MUC2, ZO-1, claudin-3, and occluding to protect the intestinal barrier. 36553765 6 16 theme Staphylococcus 1241:1254 arg1 abundance 1215:1223 the abundance 1211:1223 the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella 1211:1280 Furthermore, GLE modulated the composition of gut microbiota disturbed by DSS, as it decreased the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella, and increased Turicibacter and Bifidobacterium. 36553765 6 17 theme gut 1162:1164 arg1 microbiota 1166:1175 gut microbiota 1162:1175 gut microbiota disturbed by DSS 1162:1192 Furthermore, GLE modulated the composition of gut microbiota disturbed by DSS, as it decreased the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella, and increased Turicibacter and Bifidobacterium. 36553765 2 18 theme incarnatum 369:378 arg1 effects 323:329 the prebiotic effects 309:329 the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation 309:400 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 19 theme sulphate 640:647 arg1 DSS 657:659 DSS 657:659 DSS 657:659 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 19 theme sulphate 640:647 arg1 sodium 649:654 dextran sulphate sodium 632:654 dextran sulphate sodium (DSS) administration 632:675 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 20 theme sodium 649:654 arg1 administration 662:675 dextran sulphate sodium (DSS) administration 632:675 dextran sulphate sodium (DSS) administration 632:675 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 21 theme prebiotic 313:321 arg1 effects 323:329 the prebiotic effects 309:329 the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation 309:400 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 8 22 theme TRAF6/MyD88/NF-κB 1706:1722 arg1 pathways 1734:1741 TRAF6/MyD88/NF-κB signaling pathways 1706:1741 TRAF6/MyD88/NF-κB signaling pathways 1706:1741 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 36553765 3 23 theme activity 818:825 arg1 prevention 734:743 prevention 734:743 prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices 734:833 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 3 23 theme activity 818:825 arg1 rates 727:731 reduced mortality rates 709:731 reduced mortality rates 709:731 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 3 23 theme activity 818:825 arg1 scores 852:857 histological scores 839:857 histological scores 839:857 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 3 24 theme reduced 709:715 arg1 rates 727:731 reduced mortality rates 709:731 reduced mortality rates 709:731 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 2 25 theme dextran 632:638 arg1 DSS 657:659 DSS 657:659 DSS 657:659 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 25 theme dextran 632:638 arg1 sodium 649:654 dextran sulphate sodium 632:654 dextran sulphate sodium (DSS) administration 632:675 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 0 26 theme lucidum 10:16 arg1 Extraction 26:35 Ganoderma lucidum Ethanol Extraction 0:35 Ganoderma lucidum Ethanol Extraction 0:35 Ganoderma lucidum Ethanol Extraction Promotes Dextran Sulphate Sodium Induced Colitis Recovery and Modulation in Microbiota. 36553765 3 27 theme mortality 717:725 arg1 rates 727:731 reduced mortality rates 709:731 reduced mortality rates 709:731 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 4 28 theme COX-2 860:864 arg1 activities 881:890 COX-2, MPO, and iNOS activities 860:890 COX-2, MPO, and iNOS activities 860:890 COX-2, MPO, and iNOS activities and the inflammatory cytokines' expressions were determined to demonstrate the inhibition inflammation by GLE. 36553765 4 29 theme inhibition 971:980 arg1 inflammation 982:993 the inhibition inflammation 967:993 the inhibition inflammation by GLE 967:1000 COX-2, MPO, and iNOS activities and the inflammatory cytokines' expressions were determined to demonstrate the inhibition inflammation by GLE. 36553765 4 30 theme iNOS 876:879 arg1 activities 881:890 COX-2, MPO, and iNOS activities 860:890 COX-2, MPO, and iNOS activities 860:890 COX-2, MPO, and iNOS activities and the inflammatory cytokines' expressions were determined to demonstrate the inhibition inflammation by GLE. 36553765 1 31 theme physical 208:215 arg1 health 217:222 physical health 208:222 physical health 208:222 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 1 31 theme physical 208:215 arg1 prebiotic 229:237 a prebiotic 227:237 a prebiotic 227:237 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 0 32 theme Ganoderma 0:8 arg1 lucidum 10:16 Ganoderma lucidum 0:16 Ganoderma lucidum Ethanol Extraction 0:35 Ganoderma lucidum Ethanol Extraction Promotes Dextran Sulphate Sodium Induced Colitis Recovery and Modulation in Microbiota. 36553765 3 33 theme weight 748:753 arg1 loss 755:758 weight loss 748:758 weight loss 748:758 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 2 34 theme extraction 427:436 arg1 GLP 455:457 GLP 455:457 GLP 455:457 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 34 theme extraction 427:436 arg1 polysaccharides 438:452 lucidum water extraction polysaccharides 413:452 G. lucidum water extraction polysaccharides (GLP) 410:458 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 35 theme extraction 481:490 arg1 polysaccharides 492:506 water extraction polysaccharides 475:506 G. incarnatum water extraction polysaccharides (GIP) 461:512 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 35 theme extraction 481:490 arg1 GIP 509:511 GIP 509:511 GIP 509:511 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 3 36 theme loss 755:758 arg1 prevention 734:743 prevention 734:743 prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices 734:833 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 3 36 theme loss 755:758 arg1 rates 727:731 reduced mortality rates 709:731 reduced mortality rates 709:731 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 3 36 theme loss 755:758 arg1 scores 852:857 histological scores 839:857 histological scores 839:857 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 2 37 theme administration 662:675 arg1 days 624:627 7 days 622:627 7 days of dextran sulphate sodium (DSS) administration 622:675 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 38 theme lucidum 344:350 arg1 effects 323:329 the prebiotic effects 309:329 the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation 309:400 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 39 theme water 475:479 arg1 polysaccharides 492:506 water extraction polysaccharides 475:506 G. incarnatum water extraction polysaccharides (GIP) 461:512 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 39 theme water 475:479 arg1 GIP 509:511 GIP 509:511 GIP 509:511 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 40 theme ethanol 570:576 arg1 GIE 590:592 GIE 590:592 GIE 590:592 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 40 theme ethanol 570:576 arg1 extraction 578:587 ethanol extraction 570:587 G. incarnatum ethanol extraction (GIE) 556:593 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 6 41 theme microbiota 1166:1175 arg1 composition 1147:1157 the composition 1143:1157 the composition of gut microbiota disturbed by DSS 1143:1192 Furthermore, GLE modulated the composition of gut microbiota disturbed by DSS, as it decreased the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella, and increased Turicibacter and Bifidobacterium. 36553765 2 42 theme Ganoderma 334:342 arg1 lucidum 344:350 Ganoderma lucidum 334:350 Ganoderma lucidum 334:350 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 43 theme G. 515:516 arg1 lucidum 518:524 G. lucidum ethanol extraction (GLE) 515:549 G. lucidum ethanol extraction (GLE) 515:549 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 44 theme colon 383:387 arg1 inflammation 389:400 colon inflammation 383:400 colon inflammation 383:400 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 5 45 theme claudin-3 1056:1064 arg1 levels 1034:1039 the levels 1030:1039 the levels of MUC2, ZO-1, claudin-3, and occluding 1030:1079 Meanwhile, GLE upregulated the levels of MUC2, ZO-1, claudin-3, and occluding to protect the intestinal barrier. 36553765 7 46 theme positive 1366:1373 arg1 influence 1375:1383 a positive influence 1364:1383 a positive influence 1364:1383 Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. 36553765 8 47 from response 1694:1701 arg1 pathways 1734:1741 TRAF6/MyD88/NF-κB signaling pathways 1706:1741 TRAF6/MyD88/NF-κB signaling pathways 1706:1741 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 36553765 6 48 theme Bacteroides 1228:1238 arg1 abundance 1215:1223 the abundance 1211:1223 the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella 1211:1280 Furthermore, GLE modulated the composition of gut microbiota disturbed by DSS, as it decreased the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella, and increased Turicibacter and Bifidobacterium. 36553765 3 49 theme colon 771:775 arg1 shortening 784:793 mitigated colon length shortening 761:793 mitigated colon length shortening 761:793 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 7 50 contain had 1360:1362 arg2 influence 1375:1383 a positive influence 1364:1383 a positive influence 1364:1383 Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. 36553765 7 50 contain had 1360:1362 arg1 GLE 1356:1358 GLE 1356:1358 GLE 1356:1358 Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. 36553765 3 51 theme shortening 784:793 arg1 prevention 734:743 prevention 734:743 prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices 734:833 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 3 51 theme shortening 784:793 arg1 rates 727:731 reduced mortality rates 709:731 reduced mortality rates 709:731 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 3 51 theme shortening 784:793 arg1 scores 852:857 histological scores 839:857 histological scores 839:857 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 3 52 theme length 777:782 arg1 shortening 784:793 mitigated colon length shortening 761:793 mitigated colon length shortening 761:793 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 7 53 theme TRAF6/MyD88/NF-κB 1427:1443 arg1 pathways 1455:1462 TRAF6/MyD88/NF-κB signaling pathways 1427:1462 TRAF6/MyD88/NF-κB signaling pathways 1427:1462 Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. 36553765 1 54 theme Popular 125:131 arg1 mushrooms 140:148 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum 125:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum 125:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 1 54 theme Popular 125:131 arg1 lucidum 160:166 Ganoderma lucidum 150:166 Ganoderma lucidum 150:166 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 1 54 theme Popular 125:131 arg1 incarnatum 185:194 Gloeostereum incarnatum 172:194 Gloeostereum incarnatum 172:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 8 55 theme inflammatory 1552:1563 arg1 cytokines 1565:1573 inflammatory cytokines 1552:1573 inflammatory cytokines 1552:1573 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 36553765 2 56 dep lucidum 518:524 arg1 extraction 534:543 ethanol extraction 526:543 G. lucidum ethanol extraction (GLE) 515:549 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 56 dep lucidum 518:524 arg1 GLE 546:548 GLE 546:548 GLE 546:548 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 8 57 theme mucosal 1602:1608 arg1 barrier 1610:1616 the intestinal mucosal barrier 1587:1616 the intestinal mucosal barrier 1587:1616 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 36553765 2 58 dep G. 461:462 arg1 polysaccharides 492:506 water extraction polysaccharides 475:506 G. incarnatum water extraction polysaccharides (GIP) 461:512 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 58 dep G. 461:462 arg1 GIP 509:511 GIP 509:511 GIP 509:511 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 58 dep G. 461:462 arg1 incarnatum 464:473 G. incarnatum water extraction polysaccharides (GIP) 461:512 G. incarnatum water extraction polysaccharides (GIP) 461:512 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 1 59 theme edible 133:138 arg1 mushrooms 140:148 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum 125:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum 125:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 1 59 theme edible 133:138 arg1 lucidum 160:166 Ganoderma lucidum 150:166 Ganoderma lucidum 150:166 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 1 59 theme edible 133:138 arg1 incarnatum 185:194 Gloeostereum incarnatum 172:194 Gloeostereum incarnatum 172:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 3 60 theme mitigated 761:769 arg1 shortening 784:793 mitigated colon length shortening 761:793 mitigated colon length shortening 761:793 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 5 61 theme MUC2 1044:1047 arg1 levels 1034:1039 the levels 1030:1039 the levels of MUC2, ZO-1, claudin-3, and occluding 1030:1079 Meanwhile, GLE upregulated the levels of MUC2, ZO-1, claudin-3, and occluding to protect the intestinal barrier. 36553765 7 62 theme tight 1407:1411 arg1 junction 1413:1420 tight junction 1407:1420 tight junction 1407:1420 Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. 36553765 8 63 theme immune 1687:1692 arg1 response 1694:1701 immune response 1687:1701 immune response in TRAF6/MyD88/NF-κB signaling pathways 1687:1741 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 36553765 8 64 theme GLE 1480:1482 arg1 supplementation 1484:1498 GLE supplementation 1480:1498 GLE supplementation 1480:1498 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 36553765 2 65 dep G. 410:411 arg1 GLP 455:457 GLP 455:457 GLP 455:457 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 65 dep G. 410:411 arg1 polysaccharides 438:452 lucidum water extraction polysaccharides 413:452 G. lucidum water extraction polysaccharides (GLP) 410:458 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 1 66 theme Ganoderma 150:158 arg1 mushrooms 140:148 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum 125:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum 125:194 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 1 66 theme Ganoderma 150:158 arg1 lucidum 160:166 Ganoderma lucidum 150:166 Ganoderma lucidum 150:166 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 3 67 theme histological 839:850 arg1 scores 852:857 histological scores 839:857 histological scores 839:857 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 3 68 theme decreased 800:808 arg1 activity 818:825 decreased disease activity 800:825 decreased disease activity 800:825 Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. 36553765 0 69 theme Colitis 78:84 arg1 Recovery 86:93 Dextran Sulphate Sodium Induced Colitis Recovery 46:93 Dextran Sulphate Sodium Induced Colitis Recovery 46:93 Ganoderma lucidum Ethanol Extraction Promotes Dextran Sulphate Sodium Induced Colitis Recovery and Modulation in Microbiota. 36553765 5 70 theme ZO-1 1050:1053 arg1 levels 1034:1039 the levels 1030:1039 the levels of MUC2, ZO-1, claudin-3, and occluding 1030:1079 Meanwhile, GLE upregulated the levels of MUC2, ZO-1, claudin-3, and occluding to protect the intestinal barrier. 36553765 7 71 theme cell 1339:1342 arg1 experiment 1344:1353 cell experiment 1339:1353 cell experiment 1339:1353 Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. 36553765 2 72 theme water 421:425 arg1 GLP 455:457 GLP 455:457 GLP 455:457 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 72 theme water 421:425 arg1 polysaccharides 438:452 lucidum water extraction polysaccharides 413:452 G. lucidum water extraction polysaccharides (GLP) 410:458 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 73 from effects 323:329 arg1 inflammation 389:400 colon inflammation 383:400 colon inflammation 383:400 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 1 74 theme intestinal 260:269 arg1 microbiota 271:280 intestinal microbiota 260:280 intestinal microbiota 260:280 Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. 36553765 0 75 theme Induced 70:76 arg1 Recovery 86:93 Dextran Sulphate Sodium Induced Colitis Recovery 46:93 Dextran Sulphate Sodium Induced Colitis Recovery 46:93 Ganoderma lucidum Ethanol Extraction Promotes Dextran Sulphate Sodium Induced Colitis Recovery and Modulation in Microbiota. 36553765 5 76 theme intestinal 1096:1105 arg1 barrier 1107:1113 the intestinal barrier 1092:1113 the intestinal barrier 1092:1113 Meanwhile, GLE upregulated the levels of MUC2, ZO-1, claudin-3, and occluding to protect the intestinal barrier. 36553765 0 77 theme Ethanol 18:24 arg1 Extraction 26:35 Ganoderma lucidum Ethanol Extraction 0:35 Ganoderma lucidum Ethanol Extraction 0:35 Ganoderma lucidum Ethanol Extraction Promotes Dextran Sulphate Sodium Induced Colitis Recovery and Modulation in Microbiota. 36553765 2 78 theme lucidum 413:419 arg1 GLP 455:457 GLP 455:457 GLP 455:457 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 2 78 theme lucidum 413:419 arg1 polysaccharides 438:452 lucidum water extraction polysaccharides 413:452 G. lucidum water extraction polysaccharides (GLP) 410:458 Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. 36553765 8 79 theme microbiota 1641:1650 arg1 changes 1652:1658 microbiota changes 1641:1658 microbiota changes 1641:1658 In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways. 35623093 2 0 theme water 331:335 arg1 processes 347:355 water treatment processes 331:355 water treatment processes 331:355 Currently, there is a lack of knowledge about the effect of temperature on the biofilm structure in water treatment processes. 35623093 7 1 from temperature 985:995 arg1 biofilm 970:976 the biofilm 966:976 the biofilm at low temperature 966:995 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 0 2 theme Membrane 80:87 arg1 System 95:100 a Gravity-Driven Membrane (GDM) System 63:100 a Gravity-Driven Membrane (GDM) System 63:100 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 7 3 theme lipids 1043:1048 arg1 metabolites 1028:1038 the metabolites 1024:1038 the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%) 1024:1214 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 7 4 theme lipid-like 1054:1063 arg1 molecules 1065:1073 lipid-like molecules 1054:1073 lipid-like molecules 1054:1073 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 4 5 theme oxygen 620:625 arg1 concentration 627:639 dissolved oxygen concentration 610:639 dissolved oxygen concentration 610:639 The results showed that the difference in dissolved oxygen concentration might be one of the main factors regulating the structural components of the biofilm. 35623093 0 6 from Metabolomics 152:163 arg1 Insights 103:110 Insights 103:110 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 0:164 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 9 7 theme low 1468:1470 arg1 temperature 1472:1482 low temperature 1468:1482 low temperature 1468:1482 Furthermore, the upregulation pathway of pyrimidine metabolism also increased the risk of urea accumulation at low temperature. 35623093 0 8 from Influence 0:8 arg1 Mechanisms 46:55 Biofilm Formation Mechanisms 28:55 Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System 28:100 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 4 9 theme structural 689:698 arg1 components 700:709 the structural components 685:709 the structural components of the biofilm 685:724 The results showed that the difference in dissolved oxygen concentration might be one of the main factors regulating the structural components of the biofilm. 35623093 8 10 theme more 1247:1250 arg1 polysaccharides 1252:1266 more polysaccharides 1247:1266 more polysaccharides 1247:1266 These small molecules secrete more polysaccharides having C═O and O═C-O functional groups, which intensified the resistance of the biofilm. 35623093 8 11 contain having 1268:1273 arg2 groups 1300:1305 O═C-O functional groups 1283:1305 O═C-O functional groups 1283:1305 These small molecules secrete more polysaccharides having C═O and O═C-O functional groups, which intensified the resistance of the biofilm. 35623093 8 11 contain having 1268:1273 arg2 C═O 1275:1277 C═O 1275:1277 C═O 1275:1277 These small molecules secrete more polysaccharides having C═O and O═C-O functional groups, which intensified the resistance of the biofilm. 35623093 8 11 contain having 1268:1273 arg1 polysaccharides 1252:1266 more polysaccharides 1247:1266 more polysaccharides 1247:1266 These small molecules secrete more polysaccharides having C═O and O═C-O functional groups, which intensified the resistance of the biofilm. 35623093 0 12 theme GDM 90:92 arg1 System 95:100 a Gravity-Driven Membrane (GDM) System 63:100 a Gravity-Driven Membrane (GDM) System 63:100 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 6 13 theme acid 824:827 arg1 metabolism 829:838 The linoleic acid metabolism 811:838 The linoleic acid metabolism 811:838 The linoleic acid metabolism was significantly inhibited at low temperature, resulting in enhanced pyrimidine metabolism by Na+ accumulation. 35623093 3 14 theme high 491:494 arg1 " 495:495 "high" 490:495 "high" 490:495 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 2 15 from structure 318:326 arg1 processes 347:355 water treatment processes 331:355 water treatment processes 331:355 Currently, there is a lack of knowledge about the effect of temperature on the biofilm structure in water treatment processes. 35623093 2 16 theme knowledge 261:269 arg1 lack 253:256 a lack 251:256 a lack of knowledge about the effect of temperature on the biofilm structure in water treatment processes 251:355 Currently, there is a lack of knowledge about the effect of temperature on the biofilm structure in water treatment processes. 35623093 4 17 from difference 596:605 arg1 concentration 627:639 dissolved oxygen concentration 610:639 dissolved oxygen concentration 610:639 The results showed that the difference in dissolved oxygen concentration might be one of the main factors regulating the structural components of the biofilm. 35623093 0 18 from Structures 137:146 arg1 Insights 103:110 Insights 103:110 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 0:164 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 6 19 theme linoleic 815:822 arg1 metabolism 829:838 The linoleic acid metabolism 811:838 The linoleic acid metabolism 811:838 The linoleic acid metabolism was significantly inhibited at low temperature, resulting in enhanced pyrimidine metabolism by Na+ accumulation. 35623093 4 20 theme main 661:664 arg1 factors 666:672 the main factors 657:672 the main factors regulating the structural components of the biofilm 657:724 The results showed that the difference in dissolved oxygen concentration might be one of the main factors regulating the structural components of the biofilm. 35623093 8 21 theme small 1223:1227 arg1 molecules 1229:1237 These small molecules 1217:1237 These small molecules 1217:1237 These small molecules secrete more polysaccharides having C═O and O═C-O functional groups, which intensified the resistance of the biofilm. 35623093 5 22 theme lower 792:796 arg1 temperature 798:808 the lower temperature 788:808 the lower temperature 788:808 A denser biofilm formation and reduced flux were observed at the lower temperature. 35623093 3 23 theme gravity-driven 375:388 arg1 system 415:420 a gravity-driven membrane ultrafiltration system 373:420 a gravity-driven membrane ultrafiltration system 373:420 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 7 24 theme organoheterocyclic 1179:1196 arg1 compounds 1198:1206 organoheterocyclic compounds 1179:1206 organoheterocyclic compounds (6.66%) 1179:1214 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 7 24 theme organoheterocyclic 1179:1196 arg1 % 1213:1213 6.66% 1209:1213 6.66% 1209:1213 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 7 25 theme acids 1093:1097 arg1 metabolites 1028:1038 the metabolites 1024:1038 the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%) 1024:1214 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 5 26 theme denser 729:734 arg1 formation 744:752 A denser biofilm formation 727:752 A denser biofilm formation 727:752 A denser biofilm formation and reduced flux were observed at the lower temperature. 35623093 2 27 theme temperature 291:301 arg1 effect 281:286 the effect 277:286 the effect of temperature on the biofilm structure in water treatment processes 277:355 Currently, there is a lack of knowledge about the effect of temperature on the biofilm structure in water treatment processes. 35623093 7 28 theme organic 1085:1091 arg1 % 1121:1121 10.83% 1116:1121 10.83% 1116:1121 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 7 28 theme organic 1085:1091 arg1 acids 1093:1097 organic acids 1085:1097 organic acids 1085:1097 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 3 29 theme ultrafiltration 399:413 arg1 system 415:420 a gravity-driven membrane ultrafiltration system 373:420 a gravity-driven membrane ultrafiltration system 373:420 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 5 30 theme biofilm 736:742 arg1 formation 744:752 A denser biofilm formation 727:752 A denser biofilm formation 727:752 A denser biofilm formation and reduced flux were observed at the lower temperature. 35623093 6 31 theme pyrimidine 910:919 arg1 metabolism 921:930 enhanced pyrimidine metabolism 901:930 enhanced pyrimidine metabolism by Na+ accumulation 901:950 The linoleic acid metabolism was significantly inhibited at low temperature, resulting in enhanced pyrimidine metabolism by Na+ accumulation. 35623093 10 32 theme principal 1584:1592 arg1 Limnohabitans 1485:1497 Limnohabitans 1485:1497 Limnohabitans 1485:1497 Limnohabitans, Deinococcus, Diaphorobacter, Flavobacterium, and Pseudomonas were identified as the principal microorganisms involved in this metabolic transformation. 35623093 10 32 theme principal 1584:1592 arg1 Flavobacterium 1529:1542 Flavobacterium 1529:1542 Flavobacterium 1529:1542 Limnohabitans, Deinococcus, Diaphorobacter, Flavobacterium, and Pseudomonas were identified as the principal microorganisms involved in this metabolic transformation. 35623093 10 32 theme principal 1584:1592 arg1 Pseudomonas 1549:1559 Pseudomonas 1549:1559 Pseudomonas 1549:1559 Limnohabitans, Deinococcus, Diaphorobacter, Flavobacterium, and Pseudomonas were identified as the principal microorganisms involved in this metabolic transformation. 35623093 10 32 theme principal 1584:1592 arg1 microorganisms 1594:1607 the principal microorganisms 1580:1607 the principal microorganisms involved in this metabolic transformation 1580:1649 Limnohabitans, Deinococcus, Diaphorobacter, Flavobacterium, and Pseudomonas were identified as the principal microorganisms involved in this metabolic transformation. 35623093 10 32 theme principal 1584:1592 arg1 Deinococcus 1500:1510 Deinococcus 1500:1510 Deinococcus 1500:1510 Limnohabitans, Deinococcus, Diaphorobacter, Flavobacterium, and Pseudomonas were identified as the principal microorganisms involved in this metabolic transformation. 35623093 10 32 theme principal 1584:1592 arg1 Diaphorobacter 1513:1526 Diaphorobacter 1513:1526 Diaphorobacter 1513:1526 Limnohabitans, Deinococcus, Diaphorobacter, Flavobacterium, and Pseudomonas were identified as the principal microorganisms involved in this metabolic transformation. 35623093 3 33 dep " 481:481 arg1 " 495:495 "high" 490:495 "high" 490:495 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 7 34 contain had 997:999 arg2 proportion 1010:1019 a higher proportion 1001:1019 a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%) 1001:1214 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 7 34 contain had 997:999 arg1 biofilm 970:976 the biofilm 966:976 the biofilm at low temperature 966:995 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 6 35 theme enhanced 901:908 arg1 metabolism 921:930 enhanced pyrimidine metabolism 901:930 enhanced pyrimidine metabolism by Na+ accumulation 901:950 The linoleic acid metabolism was significantly inhibited at low temperature, resulting in enhanced pyrimidine metabolism by Na+ accumulation. 35623093 1 36 theme significant 182:192 arg1 effect 194:199 a significant effect 180:199 a significant effect on water treatment processes 180:228 A biofilm has a significant effect on water treatment processes. 35623093 0 37 theme Temperature 13:23 arg1 Influence 0:8 Influence 0:8 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 0:164 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 7 38 theme higher 1003:1008 arg1 proportion 1010:1019 a higher proportion 1001:1019 a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%) 1001:1214 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 4 39 theme factors 666:672 arg1 factors 666:672 the main factors 657:672 the main factors regulating the structural components of the biofilm 657:724 The results showed that the difference in dissolved oxygen concentration might be one of the main factors regulating the structural components of the biofilm. 35623093 4 39 theme factors 666:672 arg1 one 650:652 one 650:652 one 650:652 The results showed that the difference in dissolved oxygen concentration might be one of the main factors regulating the structural components of the biofilm. 35623093 4 39 theme factors 666:672 arg1 difference 596:605 the difference 592:605 the difference in dissolved oxygen concentration 592:639 The results showed that the difference in dissolved oxygen concentration might be one of the main factors regulating the structural components of the biofilm. 35623093 3 40 dep structure 528:536 arg1 mechanism 557:565 mechanism 557:565 mechanism 557:565 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 0 41 theme Formation 36:44 arg1 Mechanisms 46:55 Biofilm Formation Mechanisms 28:55 Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System 28:100 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 9 42 theme urea 1447:1450 arg1 accumulation 1452:1463 urea accumulation 1447:1463 urea accumulation 1447:1463 Furthermore, the upregulation pathway of pyrimidine metabolism also increased the risk of urea accumulation at low temperature. 35623093 0 43 theme Community 127:135 arg1 Structures 137:146 Microbial Community Structures 117:146 Microbial Community Structures 117:146 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 1 44 contain has 176:178 arg2 effect 194:199 a significant effect 180:199 a significant effect on water treatment processes 180:228 A biofilm has a significant effect on water treatment processes. 35623093 1 44 contain has 176:178 arg1 biofilm 168:174 A biofilm 166:174 A biofilm 166:174 A biofilm has a significant effect on water treatment processes. 35623093 9 45 theme metabolism 1409:1418 arg1 pathway 1387:1393 the upregulation pathway 1370:1393 the upregulation pathway of pyrimidine metabolism 1370:1418 Furthermore, the upregulation pathway of pyrimidine metabolism also increased the risk of urea accumulation at low temperature. 35623093 0 46 theme Biofilm 28:34 arg1 Mechanisms 46:55 Biofilm Formation Mechanisms 28:55 Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System 28:100 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 0 47 theme Microbial 117:125 arg1 Structures 137:146 Microbial Community Structures 117:146 Microbial Community Structures 117:146 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 6 48 theme Na+ 935:937 arg1 accumulation 939:950 Na+ accumulation 935:950 Na+ accumulation 935:950 The linoleic acid metabolism was significantly inhibited at low temperature, resulting in enhanced pyrimidine metabolism by Na+ accumulation. 35623093 1 49 theme water 204:208 arg1 processes 220:228 water treatment processes 204:228 water treatment processes 204:228 A biofilm has a significant effect on water treatment processes. 35623093 7 50 theme molecules 1065:1073 arg1 metabolites 1028:1038 the metabolites 1024:1038 the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%) 1024:1214 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 3 51 theme low 478:480 arg1 " 481:481 "low" 477:481 "low" 477:481 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 3 51 theme low 478:480 arg1 °C 486:487 4 °C 484:487 4 °C 484:487 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 3 51 theme low 478:480 arg1 °C 501:502 25 °C 498:502 25 °C 498:502 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 8 52 theme O═C-O 1283:1287 arg1 groups 1300:1305 O═C-O functional groups 1283:1305 O═C-O functional groups 1283:1305 These small molecules secrete more polysaccharides having C═O and O═C-O functional groups, which intensified the resistance of the biofilm. 35623093 10 53 theme metabolic 1626:1634 arg1 transformation 1636:1649 this metabolic transformation 1621:1649 this metabolic transformation 1621:1649 Limnohabitans, Deinococcus, Diaphorobacter, Flavobacterium, and Pseudomonas were identified as the principal microorganisms involved in this metabolic transformation. 35623093 6 54 theme low 871:873 arg1 temperature 875:885 low temperature 871:885 low temperature 871:885 The linoleic acid metabolism was significantly inhibited at low temperature, resulting in enhanced pyrimidine metabolism by Na+ accumulation. 35623093 7 55 theme low 981:983 arg1 temperature 985:995 low temperature 981:995 low temperature 981:995 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 8 56 theme biofilm 1348:1354 arg1 resistance 1330:1339 the resistance 1326:1339 the resistance of the biofilm 1326:1354 These small molecules secrete more polysaccharides having C═O and O═C-O functional groups, which intensified the resistance of the biofilm. 35623093 7 57 theme metabolites 1028:1038 arg1 proportion 1010:1019 a higher proportion 1001:1019 a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%) 1001:1214 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 2 58 theme biofilm 310:316 arg1 structure 318:326 the biofilm structure 306:326 the biofilm structure in water treatment processes 306:355 Currently, there is a lack of knowledge about the effect of temperature on the biofilm structure in water treatment processes. 35623093 4 59 theme biofilm 718:724 arg1 components 700:709 the structural components 685:709 the structural components of the biofilm 685:724 The results showed that the difference in dissolved oxygen concentration might be one of the main factors regulating the structural components of the biofilm. 35623093 1 60 from effect 194:199 arg1 processes 220:228 water treatment processes 204:228 water treatment processes 204:228 A biofilm has a significant effect on water treatment processes. 35623093 9 61 theme upregulation 1374:1385 arg1 pathway 1387:1393 the upregulation pathway 1370:1393 the upregulation pathway of pyrimidine metabolism 1370:1418 Furthermore, the upregulation pathway of pyrimidine metabolism also increased the risk of urea accumulation at low temperature. 35623093 1 62 theme treatment 210:218 arg1 processes 220:228 water treatment processes 204:228 water treatment processes 204:228 A biofilm has a significant effect on water treatment processes. 35623093 5 63 located observed 776:783 arg2 formation 744:752 A denser biofilm formation 727:752 A denser biofilm formation 727:752 A denser biofilm formation and reduced flux were observed at the lower temperature. 35623093 5 63 located observed 776:783 arg2 flux 766:769 reduced flux 758:769 reduced flux 758:769 A denser biofilm formation and reduced flux were observed at the lower temperature. 35623093 5 63 located observed 776:783 arg1 temperature 798:808 the lower temperature 788:808 the lower temperature 788:808 A denser biofilm formation and reduced flux were observed at the lower temperature. 35623093 8 64 theme functional 1289:1298 arg1 groups 1300:1305 O═C-O functional groups 1283:1305 O═C-O functional groups 1283:1305 These small molecules secrete more polysaccharides having C═O and O═C-O functional groups, which intensified the resistance of the biofilm. 35623093 9 65 theme pyrimidine 1398:1407 arg1 metabolism 1409:1418 pyrimidine metabolism 1398:1418 pyrimidine metabolism 1398:1418 Furthermore, the upregulation pathway of pyrimidine metabolism also increased the risk of urea accumulation at low temperature. 35623093 7 66 theme compounds 1198:1206 arg1 metabolites 1028:1038 the metabolites 1024:1038 the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%) 1024:1214 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 0 67 theme Gravity-Driven 65:78 arg1 System 95:100 a Gravity-Driven Membrane (GDM) System 63:100 a Gravity-Driven Membrane (GDM) System 63:100 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 3 68 theme river 440:444 arg1 feedwater 446:454 river feedwater 440:454 river feedwater 440:454 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 3 69 theme biofilm 520:526 arg1 structure 528:536 the biofilm structure 516:536 the biofilm structure 516:536 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 5 70 theme reduced 758:764 arg1 flux 766:769 reduced flux 758:769 reduced flux 758:769 A denser biofilm formation and reduced flux were observed at the lower temperature. 35623093 4 71 theme dissolved 610:618 arg1 concentration 627:639 dissolved oxygen concentration 610:639 dissolved oxygen concentration 610:639 The results showed that the difference in dissolved oxygen concentration might be one of the main factors regulating the structural components of the biofilm. 35623093 9 72 theme accumulation 1452:1463 arg1 risk 1439:1442 the risk 1435:1442 the risk of urea accumulation 1435:1463 Furthermore, the upregulation pathway of pyrimidine metabolism also increased the risk of urea accumulation at low temperature. 35623093 3 73 dep temperatures 463:474 arg1 " 481:481 "low" 477:481 "low" 477:481 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 3 73 dep temperatures 463:474 arg1 °C 486:487 4 °C 484:487 4 °C 484:487 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 3 73 dep temperatures 463:474 arg1 °C 501:502 25 °C 498:502 25 °C 498:502 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 7 74 theme nucleosides 1125:1135 arg1 metabolites 1028:1038 the metabolites 1024:1038 the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%) 1024:1214 In addition, the biofilm at low temperature had a higher proportion of the metabolites of lipids and lipid-like molecules (11.25%), organic acids and derivatives (10.83%), nucleosides, nucleotides, and analogues (7.083%), and organoheterocyclic compounds (6.66%). 35623093 3 75 theme membrane 390:397 arg1 system 415:420 a gravity-driven membrane ultrafiltration system 373:420 a gravity-driven membrane ultrafiltration system 373:420 In this study, a gravity-driven membrane ultrafiltration system was operated with river feedwater at two temperatures ("low", 4 °C; "high", 25 °C) to explore the biofilm structure and transformation mechanism. 35623093 0 76 dep Influence 0:8 arg1 Insights 103:110 Insights 103:110 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 0:164 Influence of Temperature on Biofilm Formation Mechanisms Using a Gravity-Driven Membrane (GDM) System: Insights from Microbial Community Structures and Metabolomics. 35623093 2 77 theme treatment 337:345 arg1 processes 347:355 water treatment processes 331:355 water treatment processes 331:355 Currently, there is a lack of knowledge about the effect of temperature on the biofilm structure in water treatment processes. 35623093 2 78 from effect 281:286 arg1 structure 318:326 the biofilm structure 306:326 the biofilm structure in water treatment processes 306:355 Currently, there is a lack of knowledge about the effect of temperature on the biofilm structure in water treatment processes. 35357132 0 0 theme N-Substituted 100:112 arg1 Donors 125:130 N-Substituted β-Aminooxy Donors 100:130 N-Substituted β-Aminooxy Donors 100:130 Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors. 35357132 3 1 theme bearing/free 422:433 arg1 sugars 444:449 aldehyde bearing/free reducing sugars 413:449 aldehyde bearing/free reducing sugars 413:449 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 3 2 theme reducing 435:442 arg1 sugars 444:449 aldehyde bearing/free reducing sugars 413:449 aldehyde bearing/free reducing sugars 413:449 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 3 3 dep condition 469:477 arg1 afford 482:487 afford 482:487 to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield 479:549 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 3 4 theme aldehyde 413:420 arg1 sugars 444:449 aldehyde bearing/free reducing sugars 413:449 aldehyde bearing/free reducing sugars 413:449 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 0 5 theme Stereoselective 0:14 arg1 Construction 16:27 Stereoselective Construction 0:27 Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors. 0:131 Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors. 35357132 1 6 theme sugar 230:234 arg1 epoxides 236:243 sugar epoxides 230:243 sugar epoxides 230:243 Orthogonally protected N-substituted β-aminooxy sugars can be stereoselectively synthesized from sugar epoxides and nitrones derived from aromatic aldehydes. 35357132 3 7 theme 1,1-/1,5/1,6-disaccharide 500:524 arg1 mimetics 526:533 N-O-linked 1,1-/1,5/1,6-disaccharide mimetics 489:533 N-O-linked 1,1-/1,5/1,6-disaccharide mimetics 489:533 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 3 8 theme heating 461:467 arg1 condition 469:477 the heating condition 457:477 the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield 457:549 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 0 9 dep Protected 45:53 arg1 Interlinked 60:70 Interlinked 60:70 Interlinked 60:70 Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors. 35357132 3 10 theme good 540:543 arg1 yield 545:549 a good yield 538:549 a good yield 538:549 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 0 11 theme Protected 45:53 arg1 Mimetics 85:92 Orthogonally Protected, N-O Interlinked Disaccharide Mimetics 32:92 Orthogonally Protected, N-O Interlinked Disaccharide Mimetics 32:92 Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors. 35357132 3 12 theme N-O-linked 489:498 arg1 mimetics 526:533 N-O-linked 1,1-/1,5/1,6-disaccharide mimetics 489:533 N-O-linked 1,1-/1,5/1,6-disaccharide mimetics 489:533 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 1 13 theme aromatic 271:278 arg1 aldehydes 280:288 aromatic aldehydes 271:288 aromatic aldehydes 271:288 Orthogonally protected N-substituted β-aminooxy sugars can be stereoselectively synthesized from sugar epoxides and nitrones derived from aromatic aldehydes. 35357132 3 14 theme synthesized 363:373 arg1 sugars 384:389 The synthesized aminooxy sugars 359:389 The synthesized aminooxy sugars 359:389 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 1 15 theme protected 146:154 arg1 sugars 181:186 Orthogonally protected N-substituted β-aminooxy sugars 133:186 Orthogonally protected N-substituted β-aminooxy sugars 133:186 Orthogonally protected N-substituted β-aminooxy sugars can be stereoselectively synthesized from sugar epoxides and nitrones derived from aromatic aldehydes. 35357132 3 16 theme aminooxy 375:382 arg1 sugars 384:389 The synthesized aminooxy sugars 359:389 The synthesized aminooxy sugars 359:389 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 1 17 attach derived 258:264 arg1 aldehydes 280:288 aromatic aldehydes 271:288 aromatic aldehydes 271:288 Orthogonally protected N-substituted β-aminooxy sugars can be stereoselectively synthesized from sugar epoxides and nitrones derived from aromatic aldehydes. 35357132 1 17 attach derived 258:264 arg2 epoxides 236:243 sugar epoxides 230:243 sugar epoxides 230:243 Orthogonally protected N-substituted β-aminooxy sugars can be stereoselectively synthesized from sugar epoxides and nitrones derived from aromatic aldehydes. 35357132 3 18 link N-O-linked 489:498 arg1 mimetics 526:533 N-O-linked 1,1-/1,5/1,6-disaccharide mimetics 489:533 N-O-linked 1,1-/1,5/1,6-disaccharide mimetics 489:533 The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield. 35357132 1 19 theme N-substituted 156:168 arg1 sugars 181:186 Orthogonally protected N-substituted β-aminooxy sugars 133:186 Orthogonally protected N-substituted β-aminooxy sugars 133:186 Orthogonally protected N-substituted β-aminooxy sugars can be stereoselectively synthesized from sugar epoxides and nitrones derived from aromatic aldehydes. 35357132 2 20 theme sugar 327:331 arg1 epoxides 333:340 ester-protected sugar epoxides 311:340 ester-protected sugar epoxides 311:340 Both the ether- and ester-protected sugar epoxides can be employed. 35357132 1 21 theme β-aminooxy 170:179 arg1 sugars 181:186 Orthogonally protected N-substituted β-aminooxy sugars 133:186 Orthogonally protected N-substituted β-aminooxy sugars 133:186 Orthogonally protected N-substituted β-aminooxy sugars can be stereoselectively synthesized from sugar epoxides and nitrones derived from aromatic aldehydes. 35357132 2 22 theme ester-protected 311:325 arg1 epoxides 333:340 ester-protected sugar epoxides 311:340 ester-protected sugar epoxides 311:340 Both the ether- and ester-protected sugar epoxides can be employed. 35357132 0 23 theme Mimetics 85:92 arg1 Construction 16:27 Stereoselective Construction 0:27 Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors. 0:131 Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors. 35357132 0 24 theme Disaccharide 72:83 arg1 Mimetics 85:92 Orthogonally Protected, N-O Interlinked Disaccharide Mimetics 32:92 Orthogonally Protected, N-O Interlinked Disaccharide Mimetics 32:92 Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors. 35357132 0 25 theme β-Aminooxy 114:123 arg1 Donors 125:130 N-Substituted β-Aminooxy Donors 100:130 N-Substituted β-Aminooxy Donors 100:130 Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors. 37243063 2 0 used used 279:282 arg2 mutation 202:209 site-directed mutation 188:209 site-directed mutation of the flavivirus genome using reverse genetics techniques 188:268 Recently, site-directed mutation of the flavivirus genome using reverse genetics techniques has been used for the rapid development of attenuated vaccines. 37243063 4 1 theme sites 561:565 arg1 deletion 533:540 deletion 533:540 deletion of N-glycosylation sites in the NS1 protein 533:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 5 2 theme them 624:627 arg1 them 624:627 them 624:627 them 624:627 Ten of them (except for the N207-del mutant strain) were successfully rescued. 37243063 5 2 theme them 624:627 arg1 Ten 617:619 Ten 617:619 Ten 617:619 Ten of them (except for the N207-del mutant strain) were successfully rescued. 37243063 7 3 theme NS1 1056:1058 arg1 protein 1060:1066 the NS1 protein 1052:1066 the NS1 protein 1052:1066 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 9 4 theme dengue 1622:1627 arg1 virus 1629:1633 the dengue virus 1618:1633 the dengue virus 1618:1633 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 4 5 with strains 520:526 arg1 deletion 533:540 deletion 533:540 deletion of N-glycosylation sites in the NS1 protein 533:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 6 6 theme mutant 724:729 arg1 strain 731:736 one mutant strain 720:736 one mutant strain (N130del+207-209QQA) 720:757 Out of the ten strains, one mutant strain (N130del+207-209QQA) was found to have significantly reduced virulence through neurovirulence assay in suckling mice, but was genetically unstable. 37243063 6 6 theme mutant 724:729 arg1 N130del+207-209QQA 739:756 N130del+207-209QQA 739:756 N130del+207-209QQA 739:756 Out of the ten strains, one mutant strain (N130del+207-209QQA) was found to have significantly reduced virulence through neurovirulence assay in suckling mice, but was genetically unstable. 37243063 8 7 theme acid 1208:1211 arg1 mutations 1222:1230 five amino acid adaptive mutations 1197:1230 five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A 1197:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 7 8 theme N207Q 1032:1036 arg1 mutations 1005:1013 mutations 1005:1013 mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein 1005:1095 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 2 9 theme rapid 292:296 arg1 development 298:308 the rapid development 288:308 the rapid development of attenuated vaccines 288:331 Recently, site-directed mutation of the flavivirus genome using reverse genetics techniques has been used for the rapid development of attenuated vaccines. 37243063 9 10 theme attenuated 1659:1668 arg1 vaccines 1670:1677 its live attenuated vaccines 1650:1677 its live attenuated vaccines 1650:1677 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 7 11 theme N130K 1025:1029 arg1 mutations 1005:1013 mutations 1005:1013 mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein 1005:1095 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 2 12 theme genome 229:234 arg1 mutation 202:209 site-directed mutation 188:209 site-directed mutation of the flavivirus genome using reverse genetics techniques 188:268 Recently, site-directed mutation of the flavivirus genome using reverse genetics techniques has been used for the rapid development of attenuated vaccines. 37243063 7 13 theme # 990:990 arg1 11-puri9 991:998 a genetically stable attenuated strain #11-puri9 951:998 a genetically stable attenuated strain #11-puri9 951:998 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 8 14 theme chimeric 1166:1173 arg1 viruses 1175:1181 chimeric viruses 1166:1181 chimeric viruses 1166:1181 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 7 15 theme attenuated 972:981 arg1 11-puri9 991:998 a genetically stable attenuated strain #11-puri9 951:998 a genetically stable attenuated strain #11-puri9 951:998 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 8 16 theme virus 1246:1250 arg1 type 1252:1255 the dengue virus type four non-structural proteins NS1 and NS2A 1235:1297 the dengue virus type four non-structural proteins NS1 and NS2A 1235:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 5 17 theme mutant 654:659 arg1 strain 661:666 the N207-del mutant strain 641:666 the N207-del mutant strain 641:666 Ten of them (except for the N207-del mutant strain) were successfully rescued. 37243063 8 18 from mutations 1222:1230 arg1 type 1252:1255 the dengue virus type four non-structural proteins NS1 and NS2A 1235:1297 the dengue virus type four non-structural proteins NS1 and NS2A 1235:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 9 19 theme dengue 1457:1462 arg1 strain 1470:1475 an attenuated dengue virus strain 1443:1475 an attenuated dengue virus strain 1443:1475 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 2 20 theme reverse 242:248 arg1 techniques 259:268 reverse genetics techniques 242:268 reverse genetics techniques 242:268 Recently, site-directed mutation of the flavivirus genome using reverse genetics techniques has been used for the rapid development of attenuated vaccines. 37243063 7 21 theme purification 924:935 arg1 assay 937:941 the plaque purification assay 913:941 the plaque purification assay 913:941 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 1 22 theme vaccines 149:156 arg1 one 123:125 one 123:125 one 123:125 Live attenuated vaccine is one of the most effective vaccines against flavivirus. 37243063 1 22 theme vaccines 149:156 arg1 vaccines 149:156 the most effective vaccines 130:156 the most effective vaccines against flavivirus 130:175 Live attenuated vaccine is one of the most effective vaccines against flavivirus. 37243063 9 23 from deletion 1489:1496 arg1 site 1544:1547 the N-glycosylation site 1524:1547 the N-glycosylation site 1524:1547 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 9 24 theme N-glycosylation 1528:1542 arg1 site 1544:1547 the N-glycosylation site 1524:1547 the N-glycosylation site 1524:1547 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 0 25 theme Virus 89:93 arg1 Pathogenesis 66:77 Pathogenesis 66:77 Pathogenesis 66:77 NS1 Protein N-Linked Glycosylation Site Affects the Virulence and Pathogenesis of Dengue Virus. 37243063 0 25 theme Virus 89:93 arg1 Virulence 52:60 Virulence 52:60 Virulence 52:60 NS1 Protein N-Linked Glycosylation Site Affects the Virulence and Pathogenesis of Dengue Virus. 37243063 4 26 theme dengue 458:463 arg1 virus 465:469 dengue virus 458:469 dengue virus 458:469 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 4 27 gly N-glycosylation 545:559 arg2 sites 561:565 N-glycosylation sites 545:565 N-glycosylation sites in the NS1 protein 545:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 9 28 theme acid 1507:1510 arg1 residues 1512:1519 amino acid residues 1501:1519 amino acid residues at the N-glycosylation site 1501:1547 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 3 29 theme virus 417:421 arg1 loci 405:408 critical virulence loci 386:408 critical virulence loci of the virus 386:421 However, this technique relies on basic research of critical virulence loci of the virus. 37243063 0 30 theme NS1 0:2 arg1 Site 35:38 NS1 Protein N-Linked Glycosylation Site 0:38 NS1 Protein N-Linked Glycosylation Site 0:38 NS1 Protein N-Linked Glycosylation Site Affects the Virulence and Pathogenesis of Dengue Virus. 37243063 3 31 theme basic 368:372 arg1 research 374:381 basic research 368:381 basic research of critical virulence loci of the virus 368:421 However, this technique relies on basic research of critical virulence loci of the virus. 37243063 4 32 theme strains 520:526 arg1 total 474:478 a total 472:478 a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein 472:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 0 33 dep Virulence 52:60 arg1 the 48:50 the 48:50 the 48:50 NS1 Protein N-Linked Glycosylation Site Affects the Virulence and Pathogenesis of Dengue Virus. 37243063 0 34 theme N-Linked 12:19 arg1 Site 35:38 NS1 Protein N-Linked Glycosylation Site 0:38 NS1 Protein N-Linked Glycosylation Site 0:38 NS1 Protein N-Linked Glycosylation Site Affects the Virulence and Pathogenesis of Dengue Virus. 37243063 1 35 theme attenuated 101:110 arg1 vaccine 112:118 Live attenuated vaccine 96:118 Live attenuated vaccine 96:118 Live attenuated vaccine is one of the most effective vaccines against flavivirus. 37243063 9 36 from site 1544:1547 arg1 deletion 1489:1496 the deletion 1485:1496 the deletion of amino acid residues at the N-glycosylation site 1485:1547 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 9 36 from site 1544:1547 arg1 residues 1512:1519 amino acid residues 1501:1519 amino acid residues at the N-glycosylation site 1501:1547 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 7 37 theme NS2A 1084:1087 arg1 protein 1089:1095 the NS2A protein 1080:1095 the NS2A protein 1080:1095 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 3 38 theme virulence 395:403 arg1 loci 405:408 critical virulence loci 386:408 critical virulence loci of the virus 386:421 However, this technique relies on basic research of critical virulence loci of the virus. 37243063 4 39 theme virus 497:501 arg1 strains 520:526 eleven dengue virus type four mutant strains 483:526 eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein 483:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 8 40 used used 1353:1356 arg2 mutations 1222:1230 five amino acid adaptive mutations 1197:1230 five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A 1197:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 6 41 theme reduced 791:797 arg1 virulence 799:807 significantly reduced virulence 777:807 significantly reduced virulence 777:807 Out of the ten strains, one mutant strain (N130del+207-209QQA) was found to have significantly reduced virulence through neurovirulence assay in suckling mice, but was genetically unstable. 37243063 8 42 dep type 1252:1255 arg1 NS2A 1294:1297 NS2A 1294:1297 NS2A 1294:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 8 42 dep type 1252:1255 arg1 NS1 1286:1288 NS1 1286:1288 NS1 1286:1288 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 8 42 dep type 1252:1255 arg1 proteins 1277:1284 four non-structural proteins 1257:1284 the dengue virus type four non-structural proteins NS1 and NS2A 1235:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 8 43 theme attenuated 1374:1383 arg1 viruses 1401:1407 attenuated dengue chimeric viruses 1374:1407 attenuated dengue chimeric viruses 1374:1407 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 4 44 from deletion 533:540 arg1 protein 578:584 the NS1 protein 570:584 the NS1 protein 570:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 4 45 theme NS1 574:576 arg1 protein 578:584 the NS1 protein 570:584 the NS1 protein 570:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 8 46 theme chimeric 1392:1399 arg1 viruses 1401:1407 attenuated dengue chimeric viruses 1374:1407 attenuated dengue chimeric viruses 1374:1407 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 4 47 from protein 578:584 arg1 deletion 533:540 deletion 533:540 deletion of N-glycosylation sites in the NS1 protein 533:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 4 48 theme N-glycosylation 545:559 arg1 sites 561:565 N-glycosylation sites 545:565 N-glycosylation sites in the NS1 protein 545:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 7 49 theme T209A 1043:1047 arg1 mutations 1005:1013 mutations 1005:1013 mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein 1005:1095 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 6 50 theme suckling 841:848 arg1 mice 850:853 suckling mice 841:853 suckling mice 841:853 Out of the ten strains, one mutant strain (N130del+207-209QQA) was found to have significantly reduced virulence through neurovirulence assay in suckling mice, but was genetically unstable. 37243063 9 51 theme virus 1629:1633 arg1 pathogenesis 1602:1613 the pathogenesis 1598:1613 the pathogenesis of the dengue virus 1598:1633 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 4 52 theme mutant 513:518 arg1 strains 520:526 eleven dengue virus type four mutant strains 483:526 eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein 483:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 2 53 theme attenuated 313:322 arg1 vaccines 324:331 attenuated vaccines 313:331 attenuated vaccines 313:331 Recently, site-directed mutation of the flavivirus genome using reverse genetics techniques has been used for the rapid development of attenuated vaccines. 37243063 8 54 theme virulence 1114:1122 arg1 loci 1124:1127 the virulence loci 1110:1127 the virulence loci 1110:1127 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 6 55 from assay 832:836 arg1 mice 850:853 suckling mice 841:853 suckling mice 841:853 Out of the ten strains, one mutant strain (N130del+207-209QQA) was found to have significantly reduced virulence through neurovirulence assay in suckling mice, but was genetically unstable. 37243063 9 56 theme live 1654:1657 arg1 vaccines 1670:1677 its live attenuated vaccines 1650:1677 its live attenuated vaccines 1650:1677 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 4 57 theme attenuated 438:447 arg1 sites 449:453 the attenuated sites 434:453 the attenuated sites in dengue virus 434:469 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 8 58 theme amino 1202:1206 arg1 mutations 1222:1230 five amino acid adaptive mutations 1197:1230 five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A 1197:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 8 59 theme revertant 1145:1153 arg1 mutant 1155:1160 revertant mutant 1145:1160 revertant mutant 1145:1160 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 8 60 theme adaptive 1213:1220 arg1 mutations 1222:1230 five amino acid adaptive mutations 1197:1230 five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A 1197:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 2 61 theme flavivirus 218:227 arg1 genome 229:234 the flavivirus genome 214:234 the flavivirus genome using reverse genetics techniques 214:268 Recently, site-directed mutation of the flavivirus genome using reverse genetics techniques has been used for the rapid development of attenuated vaccines. 37243063 5 62 theme N207-del 645:652 arg1 strain 661:666 the N207-del mutant strain 641:666 the N207-del mutant strain 641:666 Ten of them (except for the N207-del mutant strain) were successfully rescued. 37243063 7 63 theme strain 983:988 arg1 11-puri9 991:998 a genetically stable attenuated strain #11-puri9 951:998 a genetically stable attenuated strain #11-puri9 951:998 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 9 64 theme attenuated 1446:1455 arg1 strain 1470:1475 an attenuated dengue virus strain 1443:1475 an attenuated dengue virus strain 1443:1475 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 8 65 theme dengue 1239:1244 arg1 type 1252:1255 the dengue virus type four non-structural proteins NS1 and NS2A 1235:1297 the dengue virus type four non-structural proteins NS1 and NS2A 1235:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 2 66 theme genetics 250:257 arg1 techniques 259:268 reverse genetics techniques 242:268 reverse genetics techniques 242:268 Recently, site-directed mutation of the flavivirus genome using reverse genetics techniques has been used for the rapid development of attenuated vaccines. 37243063 7 67 theme stable 965:970 arg1 11-puri9 991:998 a genetically stable attenuated strain #11-puri9 951:998 a genetically stable attenuated strain #11-puri9 951:998 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 9 68 theme virus 1464:1468 arg1 strain 1470:1475 an attenuated dengue virus strain 1443:1475 an attenuated dengue virus strain 1443:1475 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 6 69 contain have 772:775 arg1 strain 731:736 one mutant strain 720:736 one mutant strain (N130del+207-209QQA) 720:757 Out of the ten strains, one mutant strain (N130del+207-209QQA) was found to have significantly reduced virulence through neurovirulence assay in suckling mice, but was genetically unstable. 37243063 6 69 contain have 772:775 arg2 virulence 799:807 significantly reduced virulence 777:807 significantly reduced virulence 777:807 Out of the ten strains, one mutant strain (N130del+207-209QQA) was found to have significantly reduced virulence through neurovirulence assay in suckling mice, but was genetically unstable. 37243063 6 69 contain have 772:775 arg1 N130del+207-209QQA 739:756 N130del+207-209QQA 739:756 N130del+207-209QQA 739:756 Out of the ten strains, one mutant strain (N130del+207-209QQA) was found to have significantly reduced virulence through neurovirulence assay in suckling mice, but was genetically unstable. 37243063 0 70 theme Dengue 82:87 arg1 Virus 89:93 Dengue Virus 82:93 Dengue Virus 82:93 NS1 Protein N-Linked Glycosylation Site Affects the Virulence and Pathogenesis of Dengue Virus. 37243063 1 71 theme effective 139:147 arg1 vaccines 149:156 the most effective vaccines 130:156 the most effective vaccines against flavivirus 130:175 Live attenuated vaccine is one of the most effective vaccines against flavivirus. 37243063 4 72 from sites 449:453 arg1 virus 465:469 dengue virus 458:469 dengue virus 458:469 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 4 73 theme dengue 490:495 arg1 strains 520:526 eleven dengue virus type four mutant strains 483:526 eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein 483:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 8 74 theme non-structural 1262:1275 arg1 NS2A 1294:1297 NS2A 1294:1297 NS2A 1294:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 8 74 theme non-structural 1262:1275 arg1 NS1 1286:1288 NS1 1286:1288 NS1 1286:1288 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 8 74 theme non-structural 1262:1275 arg1 proteins 1277:1284 four non-structural proteins 1257:1284 the dengue virus type four non-structural proteins NS1 and NS2A 1235:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 7 75 from protein 1089:1095 arg1 mutations 1005:1013 mutations 1005:1013 mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein 1005:1095 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 4 76 from sites 561:565 arg1 protein 578:584 the NS1 protein 570:584 the NS1 protein 570:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 7 77 theme plaque 917:922 arg1 assay 937:941 the plaque purification assay 913:941 the plaque purification assay 913:941 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 9 78 theme amino 1501:1505 arg1 residues 1512:1519 amino acid residues 1501:1519 amino acid residues at the N-glycosylation site 1501:1547 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 7 79 from mutations 1005:1013 arg1 protein 1060:1066 the NS1 protein 1052:1066 the NS1 protein 1052:1066 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 7 79 from mutations 1005:1013 arg1 protein 1089:1095 the NS2A protein 1080:1095 the NS2A protein 1080:1095 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 0 80 theme Protein 4:10 arg1 Site 35:38 NS1 Protein N-Linked Glycosylation Site 0:38 NS1 Protein N-Linked Glycosylation Site 0:38 NS1 Protein N-Linked Glycosylation Site Affects the Virulence and Pathogenesis of Dengue Virus. 37243063 9 81 theme residues 1512:1519 arg1 deletion 1489:1496 the deletion 1485:1496 the deletion of amino acid residues at the N-glycosylation site 1485:1547 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 3 82 theme critical 386:393 arg1 loci 405:408 critical virulence loci 386:408 critical virulence loci of the virus 386:421 However, this technique relies on basic research of critical virulence loci of the virus. 37243063 0 83 theme Glycosylation 21:33 arg1 Site 35:38 NS1 Protein N-Linked Glycosylation Site 0:38 NS1 Protein N-Linked Glycosylation Site 0:38 NS1 Protein N-Linked Glycosylation Site Affects the Virulence and Pathogenesis of Dengue Virus. 37243063 7 84 theme Further 886:892 arg1 purification 894:905 Further purification 886:905 Further purification using the plaque purification assay 886:941 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 1 85 theme Live 96:99 arg1 vaccine 112:118 Live attenuated vaccine 96:118 Live attenuated vaccine 96:118 Live attenuated vaccine is one of the most effective vaccines against flavivirus. 37243063 6 86 theme neurovirulence 817:830 arg1 assay 832:836 neurovirulence assay 817:836 neurovirulence assay in suckling mice 817:853 Out of the ten strains, one mutant strain (N130del+207-209QQA) was found to have significantly reduced virulence through neurovirulence assay in suckling mice, but was genetically unstable. 37243063 8 87 dep proteins 1277:1284 arg1 NS2A 1294:1297 NS2A 1294:1297 NS2A 1294:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 8 87 dep proteins 1277:1284 arg1 NS1 1286:1288 NS1 1286:1288 NS1 1286:1288 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 8 87 dep proteins 1277:1284 arg1 proteins 1277:1284 four non-structural proteins 1257:1284 the dengue virus type four non-structural proteins NS1 and NS2A 1235:1297 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 4 88 theme type 503:506 arg1 strains 520:526 eleven dengue virus type four mutant strains 483:526 eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein 483:584 To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. 37243063 7 89 theme E99D 1072:1075 arg1 mutations 1005:1013 mutations 1005:1013 mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein 1005:1095 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 3 90 theme loci 405:408 arg1 research 374:381 basic research 368:381 basic research of critical virulence loci of the virus 368:421 However, this technique relies on basic research of critical virulence loci of the virus. 37243063 7 91 from protein 1060:1066 arg1 mutations 1005:1013 mutations 1005:1013 mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein 1005:1095 Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. 37243063 9 92 theme theoretical 1562:1572 arg1 basis 1574:1578 a theoretical basis 1560:1578 a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines 1560:1677 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 37243063 2 93 theme site-directed 188:200 arg1 mutation 202:209 site-directed mutation 188:209 site-directed mutation of the flavivirus genome using reverse genetics techniques 188:268 Recently, site-directed mutation of the flavivirus genome using reverse genetics techniques has been used for the rapid development of attenuated vaccines. 37243063 2 94 theme vaccines 324:331 arg1 development 298:308 the rapid development 288:308 the rapid development of attenuated vaccines 288:331 Recently, site-directed mutation of the flavivirus genome using reverse genetics techniques has been used for the rapid development of attenuated vaccines. 37243063 8 95 theme dengue 1385:1390 arg1 viruses 1401:1407 attenuated dengue chimeric viruses 1374:1407 attenuated dengue chimeric viruses 1374:1407 Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. 37243063 9 96 gly N-glycosylation 1528:1542 arg2 site 1544:1547 the N-glycosylation site 1524:1547 the N-glycosylation site 1524:1547 Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines. 35921972 5 0 theme glycolytic 604:613 arg1 enzymes 615:621 critical glycolytic enzymes 595:621 critical glycolytic enzymes 595:621 Mechanistically, pyrimidine biosynthesis augmented Notch signaling and transcriptionally increased c-Myc expression, leading to up-regulation of critical glycolytic enzymes. 35921972 1 1 theme malignancies 152:163 arg1 types 143:147 multiple types 134:147 multiple types of malignancies 134:163 Metabolic reprogramming is a hallmark in multiple types of malignancies. 35921972 6 2 theme post-translational 724:741 arg1 glycosylation 752:764 post-translational N-linked glycosylation 724:764 post-translational N-linked glycosylation level 724:770 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 35921972 0 3 theme gastric 77:83 arg1 cancer 85:90 gastric cancer 77:90 gastric cancer 77:90 De novo pyrimidine synthesis fuels glycolysis and confers chemoresistance in gastric cancer. 35921972 7 4 dep synthesis 907:915 arg1 CAD 917:919 CAD 917:919 CAD 917:919 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 0 5 from chemoresistance 58:72 arg1 cancer 85:90 gastric cancer 77:90 gastric cancer 77:90 De novo pyrimidine synthesis fuels glycolysis and confers chemoresistance in gastric cancer. 35921972 7 6 theme cancer 984:989 arg1 resistance 962:971 the chemotherapeutic resistance 941:971 the chemotherapeutic resistance of gastric cancer 941:989 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 7 7 theme pathway 1076:1082 arg1 inhibition 1038:1047 pharmacologic inhibition 1024:1047 pharmacologic inhibition of pyrimidine biosynthetic pathway 1024:1082 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 5 8 theme pyrimidine 467:476 arg1 biosynthesis 478:489 pyrimidine biosynthesis 467:489 pyrimidine biosynthesis 467:489 Mechanistically, pyrimidine biosynthesis augmented Notch signaling and transcriptionally increased c-Myc expression, leading to up-regulation of critical glycolytic enzymes. 35921972 6 9 dep cleavage 794:801 arg1 the 790:792 the 790:792 the 790:792 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 35921972 4 10 theme cancer 436:441 arg1 cells 443:447 cancer cells 436:447 cancer cells 436:447 Herein, we found that de novo pyrimidine synthesis enhanced aerobic glycolysis in cancer cells. 35921972 6 11 theme Notch 821:825 arg1 cleavage 794:801 cleavage 794:801 cleavage 794:801 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 35921972 6 11 theme Notch 821:825 arg1 activation 807:816 activation 807:816 activation 807:816 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 35921972 8 12 theme chemotherapy 1300:1311 arg1 efficacy 1313:1320 chemotherapy efficacy 1300:1320 chemotherapy efficacy in gastric cancer 1300:1338 Collectively, our findings provide more insights into the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer. 35921972 8 13 theme more 1181:1184 arg1 insights 1186:1193 more insights 1181:1193 more insights into the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer 1181:1338 Collectively, our findings provide more insights into the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer. 35921972 7 14 theme biosynthetic 1063:1074 arg1 pathway 1076:1082 pyrimidine biosynthetic pathway 1052:1082 pyrimidine biosynthetic pathway 1052:1082 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 6 15 theme γ-secretase 691:701 arg1 Nicastrin 711:719 γ-secretase subunit Nicastrin 691:719 γ-secretase subunit Nicastrin 691:719 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 35921972 7 16 theme chemotherapeutic 945:960 arg1 resistance 962:971 the chemotherapeutic resistance 941:971 the chemotherapeutic resistance of gastric cancer 941:989 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 6 17 theme subunit 703:709 arg1 Nicastrin 711:719 γ-secretase subunit Nicastrin 691:719 γ-secretase subunit Nicastrin 691:719 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 35921972 7 18 dep de 888:889 arg1 novo 891:894 novo 891:894 novo 891:894 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 4 19 theme pyrimidine 384:393 arg1 synthesis 395:403 de novo pyrimidine synthesis 376:403 de novo pyrimidine synthesis 376:403 Herein, we found that de novo pyrimidine synthesis enhanced aerobic glycolysis in cancer cells. 35921972 0 20 theme De 0:1 arg1 synthesis 19:27 De novo pyrimidine synthesis 0:27 De novo pyrimidine synthesis 0:27 De novo pyrimidine synthesis fuels glycolysis and confers chemoresistance in gastric cancer. 35921972 4 21 theme aerobic 414:420 arg1 glycolysis 422:431 aerobic glycolysis 414:431 aerobic glycolysis 414:431 Herein, we found that de novo pyrimidine synthesis enhanced aerobic glycolysis in cancer cells. 35921972 1 22 theme Metabolic 93:101 arg1 reprogramming 103:115 Metabolic reprogramming 93:115 Metabolic reprogramming 93:115 Metabolic reprogramming is a hallmark in multiple types of malignancies. 35921972 1 22 theme Metabolic 93:101 arg1 hallmark 122:129 a hallmark 120:129 a hallmark in multiple types of malignancies 120:163 Metabolic reprogramming is a hallmark in multiple types of malignancies. 35921972 1 23 from hallmark 122:129 arg1 types 143:147 multiple types 134:147 multiple types of malignancies 134:163 Metabolic reprogramming is a hallmark in multiple types of malignancies. 35921972 4 24 dep de 376:377 arg1 novo 379:382 novo 379:382 novo 379:382 Herein, we found that de novo pyrimidine synthesis enhanced aerobic glycolysis in cancer cells. 35921972 0 25 theme pyrimidine 8:17 arg1 synthesis 19:27 De novo pyrimidine synthesis 0:27 De novo pyrimidine synthesis 0:27 De novo pyrimidine synthesis fuels glycolysis and confers chemoresistance in gastric cancer. 35921972 8 26 from efficacy 1313:1320 arg1 cancer 1333:1338 gastric cancer 1325:1338 gastric cancer 1325:1338 Collectively, our findings provide more insights into the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer. 35921972 5 27 theme increased 539:547 arg1 expression 555:564 transcriptionally increased c-Myc expression 521:564 transcriptionally increased c-Myc expression 521:564 Mechanistically, pyrimidine biosynthesis augmented Notch signaling and transcriptionally increased c-Myc expression, leading to up-regulation of critical glycolytic enzymes. 35921972 7 28 theme pyrimidine 896:905 arg1 synthesis 907:915 de novo pyrimidine synthesis CAD and DHODH 888:929 synthesis 907:915 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 8 29 theme glycolysis 1226:1235 arg1 regulation 1204:1213 the regulation 1200:1213 the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer 1200:1338 Collectively, our findings provide more insights into the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer. 35921972 7 30 theme cancer 1095:1100 arg1 cells 1102:1106 cancer cells 1095:1106 cancer cells 1095:1106 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 2 31 theme energy 261:266 arg1 production 268:277 excessive energy production 251:277 excessive energy production 251:277 Fast-growing cancer cells require facilitated synthesis of essential metabolites and excessive energy production. 35921972 5 32 theme c-Myc 549:553 arg1 expression 555:564 transcriptionally increased c-Myc expression 521:564 transcriptionally increased c-Myc expression 521:564 Mechanistically, pyrimidine biosynthesis augmented Notch signaling and transcriptionally increased c-Myc expression, leading to up-regulation of critical glycolytic enzymes. 35921972 6 33 theme pyrimidine 654:663 arg1 synthesis 665:673 pyrimidine synthesis 654:673 pyrimidine synthesis 654:673 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 35921972 8 34 theme aerobic 1218:1224 arg1 glycolysis 1226:1235 aerobic glycolysis 1218:1235 aerobic glycolysis 1218:1235 Collectively, our findings provide more insights into the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer. 35921972 2 35 theme cancer 179:184 arg1 cells 186:190 Fast-growing cancer cells 166:190 Fast-growing cancer cells 166:190 Fast-growing cancer cells require facilitated synthesis of essential metabolites and excessive energy production. 35921972 2 36 theme excessive 251:259 arg1 production 268:277 excessive energy production 251:277 excessive energy production 251:277 Fast-growing cancer cells require facilitated synthesis of essential metabolites and excessive energy production. 35921972 5 37 theme enzymes 615:621 arg1 up-regulation 578:590 up-regulation 578:590 up-regulation of critical glycolytic enzymes 578:621 Mechanistically, pyrimidine biosynthesis augmented Notch signaling and transcriptionally increased c-Myc expression, leading to up-regulation of critical glycolytic enzymes. 35921972 7 38 theme enzymes 876:882 arg1 up-regulation 851:863 up-regulation 851:863 up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH 851:929 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 7 39 theme de 888:889 arg1 synthesis 907:915 de novo pyrimidine synthesis CAD and DHODH 888:929 synthesis 907:915 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 2 40 theme Fast-growing 166:177 arg1 cells 186:190 Fast-growing cancer cells 166:190 Fast-growing cancer cells 166:190 Fast-growing cancer cells require facilitated synthesis of essential metabolites and excessive energy production. 35921972 8 41 theme vulnerability 1253:1265 arg1 regulation 1204:1213 the regulation 1200:1213 the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer 1200:1338 Collectively, our findings provide more insights into the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer. 35921972 7 42 theme key 872:874 arg1 enzymes 876:882 the key enzymes 868:882 the key enzymes for de novo pyrimidine synthesis CAD and DHODH 868:929 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 2 43 theme essential 225:233 arg1 metabolites 235:245 essential metabolites 225:245 essential metabolites 225:245 Fast-growing cancer cells require facilitated synthesis of essential metabolites and excessive energy production. 35921972 2 44 theme metabolites 235:245 arg1 synthesis 212:220 facilitated synthesis 200:220 facilitated synthesis of essential metabolites 200:245 Fast-growing cancer cells require facilitated synthesis of essential metabolites and excessive energy production. 35921972 2 44 theme metabolites 235:245 arg1 production 268:277 excessive energy production 251:277 excessive energy production 251:277 Fast-growing cancer cells require facilitated synthesis of essential metabolites and excessive energy production. 35921972 7 45 theme pharmacologic 1024:1036 arg1 inhibition 1038:1047 pharmacologic inhibition 1024:1047 pharmacologic inhibition of pyrimidine biosynthetic pathway 1024:1082 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 7 46 theme pyrimidine 1052:1061 arg1 pathway 1076:1082 pyrimidine biosynthetic pathway 1052:1082 pyrimidine biosynthetic pathway 1052:1082 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 6 47 link N-linked 743:750 arg1 glycosylation 752:764 post-translational N-linked glycosylation 724:764 post-translational N-linked glycosylation level 724:770 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 35921972 4 48 theme de 376:377 arg1 synthesis 395:403 de novo pyrimidine synthesis 376:403 de novo pyrimidine synthesis 376:403 Herein, we found that de novo pyrimidine synthesis enhanced aerobic glycolysis in cancer cells. 35921972 8 49 theme metabolic 1243:1251 arg1 vulnerability 1253:1265 a metabolic vulnerability 1241:1265 a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer 1241:1338 Collectively, our findings provide more insights into the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer. 35921972 7 50 theme gastric 976:982 arg1 cancer 984:989 gastric cancer 976:989 gastric cancer 976:989 Besides, we found that up-regulation of the key enzymes for de novo pyrimidine synthesis CAD and DHODH conferred the chemotherapeutic resistance of gastric cancer via accelerating glycolysis, and pharmacologic inhibition of pyrimidine biosynthetic pathway sensitized cancer cells to chemotherapy in vitro and in vivo. 35921972 1 51 theme multiple 134:141 arg1 types 143:147 multiple types 134:147 multiple types of malignancies 134:163 Metabolic reprogramming is a hallmark in multiple types of malignancies. 35921972 5 52 theme Notch 501:505 arg1 signaling 507:515 Notch signaling 501:515 Notch signaling 501:515 Mechanistically, pyrimidine biosynthesis augmented Notch signaling and transcriptionally increased c-Myc expression, leading to up-regulation of critical glycolytic enzymes. 35921972 2 53 theme facilitated 200:210 arg1 synthesis 212:220 facilitated synthesis 200:220 facilitated synthesis of essential metabolites 200:245 Fast-growing cancer cells require facilitated synthesis of essential metabolites and excessive energy production. 35921972 6 54 theme glycosylation 752:764 arg1 level 766:770 post-translational N-linked glycosylation level 724:770 post-translational N-linked glycosylation level 724:770 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 35921972 6 55 theme Further 624:630 arg1 studies 632:638 Further studies 624:638 Further studies 624:638 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 35921972 0 56 dep De 0:1 arg1 novo 3:6 novo 3:6 novo 3:6 De novo pyrimidine synthesis fuels glycolysis and confers chemoresistance in gastric cancer. 35921972 5 57 theme critical 595:602 arg1 enzymes 615:621 critical glycolytic enzymes 595:621 critical glycolytic enzymes 595:621 Mechanistically, pyrimidine biosynthesis augmented Notch signaling and transcriptionally increased c-Myc expression, leading to up-regulation of critical glycolytic enzymes. 35921972 8 58 theme gastric 1325:1331 arg1 cancer 1333:1338 gastric cancer 1325:1338 gastric cancer 1325:1338 Collectively, our findings provide more insights into the regulation of aerobic glycolysis and a metabolic vulnerability that can be exploited to enhance chemotherapy efficacy in gastric cancer. 35921972 6 59 theme N-linked 743:750 arg1 glycosylation 752:764 post-translational N-linked glycosylation 724:764 post-translational N-linked glycosylation level 724:770 Further studies revealed that pyrimidine synthesis could stabilize γ-secretase subunit Nicastrin at post-translational N-linked glycosylation level, thereby inducing the cleavage and activation of Notch. 36444016 6 0 dep bacteria 924:931 arg1 Akkermansia 982:992 Akkermansia 982:992 Akkermansia 982:992 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 36444016 6 0 dep bacteria 924:931 arg1 Faecalibacterium 947:962 Faecalibacterium 947:962 Faecalibacterium 947:962 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 36444016 6 1 theme bacteria 924:931 arg1 abundance 900:908 the abundance 896:908 the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia) 896:993 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 36444016 7 2 theme new 1137:1139 arg1 insights 1141:1148 new insights 1137:1148 new insights into the hypolipidemic mechanism of TP and EGCG 1137:1196 The above results provided new insights into the hypolipidemic mechanism of TP and EGCG. 36444016 4 3 theme body 572:575 arg1 weight 577:582 body weight 572:582 body weight 572:582 Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. 36444016 0 4 theme gut 117:119 arg1 microbiota 121:130 remodeling gut microbiota 106:130 remodeling gut microbiota 106:130 Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota. 36444016 6 5 theme beneficial 913:922 arg1 bacteria 924:931 beneficial bacteria 913:931 beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia) 913:993 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 36444016 7 6 theme above 1114:1118 arg1 results 1120:1126 The above results 1110:1126 The above results 1110:1126 The above results provided new insights into the hypolipidemic mechanism of TP and EGCG. 36444016 0 7 theme remodeling 106:115 arg1 microbiota 121:130 remodeling gut microbiota 106:130 remodeling gut microbiota 106:130 Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota. 36444016 7 8 theme EGCG 1193:1196 arg1 mechanism 1173:1181 the hypolipidemic mechanism 1155:1181 the hypolipidemic mechanism of TP and EGCG 1155:1196 The above results provided new insights into the hypolipidemic mechanism of TP and EGCG. 36444016 4 9 theme high-fat 703:710 arg1 diet 712:715 the high-fat diet 699:715 the high-fat diet 699:715 Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. 36444016 5 10 theme high-fat 811:818 arg1 diet 820:823 high-fat diet 811:823 high-fat diet intervention 811:836 Moreover, EGCG may protect liver function via reducing the glycerophospholipids increased by high-fat diet intervention. 36444016 4 11 theme cholesterol 635:645 arg1 decrease 617:624 the decrease 613:624 the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet 613:715 Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. 36444016 7 12 theme TP 1186:1187 arg1 mechanism 1173:1181 the hypolipidemic mechanism 1155:1181 the hypolipidemic mechanism of TP and EGCG 1155:1196 The above results provided new insights into the hypolipidemic mechanism of TP and EGCG. 36444016 2 13 theme blood 327:331 arg1 levels 339:344 blood lipid levels 327:344 blood lipid levels 327:344 Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. 36444016 3 14 theme EGCG 420:423 arg1 effects 402:408 the effects 398:408 the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics 398:524 This study aimed to investigate the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics. 36444016 0 15 theme Tea 0:2 arg1 polyphenol 4:13 Tea polyphenol 0:13 Tea polyphenol 0:13 Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota. 36444016 6 16 dep such 1071:1074 arg1 as 1076:1077 as 1076:1077 as 1076:1077 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 36444016 4 17 theme triglycerides 651:663 arg1 decrease 617:624 the decrease 613:624 the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet 613:715 Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. 36444016 0 18 theme epigallocatechin 19:34 arg1 gallate 36:42 epigallocatechin gallate 19:42 epigallocatechin gallate 19:42 Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota. 36444016 3 19 theme fat 465:467 arg1 accumulation 469:480 liver fat accumulation 459:480 liver fat accumulation 459:480 This study aimed to investigate the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics. 36444016 4 20 from decrease 617:624 arg1 rats 683:686 hyperlipidemic rats 668:686 hyperlipidemic rats induced by the high-fat diet 668:715 Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. 36444016 1 21 theme gut 238:240 arg1 health 242:247 gut health 238:247 gut health 238:247 Hyperlipidemia can directly cause metabolic diseases that seriously endanger disorder and metabolism and gut health. 36444016 3 22 theme TP 413:414 arg1 effects 402:408 the effects 398:408 the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics 398:524 This study aimed to investigate the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics. 36444016 6 23 theme acid-producing 1046:1059 arg1 bacteria 1061:1068 the acid-producing bacteria 1042:1068 the acid-producing bacteria (such as Butyricimonas, Desulfovibrio) 1042:1107 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 36444016 4 24 theme serum 629:633 arg1 cholesterol 635:645 serum cholesterol 629:645 serum cholesterol 629:645 Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. 36444016 7 25 theme hypolipidemic 1159:1171 arg1 mechanism 1173:1181 the hypolipidemic mechanism 1155:1181 the hypolipidemic mechanism of TP and EGCG 1155:1196 The above results provided new insights into the hypolipidemic mechanism of TP and EGCG. 36444016 6 26 theme microbiota 860:869 arg1 composition 871:881 the gut microbiota composition 852:881 the gut microbiota composition 852:881 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 36444016 5 27 theme diet 820:823 arg1 intervention 825:836 high-fat diet intervention 811:836 high-fat diet intervention 811:836 Moreover, EGCG may protect liver function via reducing the glycerophospholipids increased by high-fat diet intervention. 36444016 3 28 theme liver 459:463 arg1 accumulation 469:480 liver fat accumulation 459:480 liver fat accumulation 459:480 This study aimed to investigate the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics. 36444016 6 29 theme gut 856:858 arg1 composition 871:881 the gut microbiota composition 852:881 the gut microbiota composition 852:881 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 36444016 2 30 theme gut 350:352 arg1 microbiota 354:363 gut microbiota 350:363 gut microbiota 350:363 Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. 36444016 2 31 theme Tea 250:252 arg1 TP 266:267 TP 266:267 TP 266:267 Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. 36444016 2 31 theme Tea 250:252 arg1 polyphenol 254:263 Tea polyphenol 250:263 Tea polyphenol (TP) 250:268 Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. 36444016 6 32 dep bacteria 1061:1068 arg1 Desulfovibrio 1094:1106 Desulfovibrio 1094:1106 Desulfovibrio 1094:1106 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 36444016 6 32 dep bacteria 1061:1068 arg1 Butyricimonas 1079:1091 Butyricimonas 1079:1091 Butyricimonas 1079:1091 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 36444016 2 33 theme epigallocatechin 274:289 arg1 EGCG 300:303 EGCG 300:303 EGCG 300:303 Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. 36444016 2 33 theme epigallocatechin 274:289 arg1 gallate 291:297 epigallocatechin gallate 274:297 epigallocatechin gallate (EGCG) 274:304 Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. 36444016 2 34 theme lipid 333:337 arg1 levels 339:344 blood lipid levels 327:344 blood lipid levels 327:344 Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. 36444016 0 35 theme liver 85:89 arg1 metabolism 91:100 liver metabolism 85:100 liver metabolism 85:100 Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota. 36444016 1 36 theme metabolic 167:175 arg1 diseases 177:184 metabolic diseases 167:184 metabolic diseases that seriously endanger disorder and metabolism and gut health 167:247 Hyperlipidemia can directly cause metabolic diseases that seriously endanger disorder and metabolism and gut health. 36444016 5 37 theme liver 745:749 arg1 function 751:758 liver function 745:758 liver function 745:758 Moreover, EGCG may protect liver function via reducing the glycerophospholipids increased by high-fat diet intervention. 36444016 4 38 theme hyperlipidemic 668:681 arg1 rats 683:686 hyperlipidemic rats 668:686 hyperlipidemic rats induced by the high-fat diet 668:715 Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. 36444016 6 39 theme gut 1017:1019 arg1 health 1021:1026 gut health 1017:1026 gut health 1017:1026 TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). 37241456 0 0 theme Powder 68:73 arg1 Flammability 47:58 Flammability 47:58 Flammability 47:58 The Components' Roles in Thermal Stability and Flammability of Cork Powder. 37241456 0 0 theme Powder 68:73 arg1 Stability 33:41 Thermal Stability 25:41 Thermal Stability 25:41 The Components' Roles in Thermal Stability and Flammability of Cork Powder. 37241456 9 1 theme condensed 1548:1556 arg1 mode 1558:1561 their prominent condensed mode 1532:1561 their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process 1532:1655 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 7 2 with flammability 1109:1120 arg1 peak 1129:1132 a peak 1127:1132 a peak of heat release rate (pHRR) of 365 W/g 1127:1171 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 9 3 theme lower 1515:1519 arg1 HRR 1521:1523 lower HRR 1515:1523 lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process 1515:1655 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 0 4 theme Cork 63:66 arg1 Powder 68:73 Cork Powder 63:73 Cork Powder 63:73 The Components' Roles in Thermal Stability and Flammability of Cork Powder. 37241456 9 5 theme significant 1436:1446 arg1 ability 1457:1463 significant charring ability 1436:1463 significant charring ability 1436:1463 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 1 6 theme extractives 123:133 arg1 influence 110:118 the influence 106:118 the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. 106:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 9 7 dep mass 1594:1597 arg1 process 1649:1655 the combustion process 1634:1655 the combustion process 1634:1655 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 7 8 theme combustion 1206:1215 arg1 MCC 1230:1232 MCC 1230:1232 MCC 1230:1232 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 7 8 theme combustion 1206:1215 arg1 calorimetry 1217:1227 micro-scale combustion calorimetry 1194:1227 micro-scale combustion calorimetry (MCC) 1194:1233 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 9 9 theme charring 1448:1455 arg1 ability 1457:1463 significant charring ability 1436:1463 significant charring ability 1436:1463 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 3 10 theme polysaccharides 451:465 arg1 lignin 436:441 lignin 436:441 lignin 436:441 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 10 theme polysaccharides 451:465 arg1 % 473:473 14% 471:473 14% of extractives 471:488 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 10 theme polysaccharides 451:465 arg1 extractives 478:488 extractives 478:488 extractives 478:488 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 10 theme polysaccharides 451:465 arg1 % 446:446 19% 444:446 19% of polysaccharides 444:465 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 10 theme polysaccharides 451:465 arg1 % 431:431 24% 429:431 24% of lignin 429:441 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 10 theme polysaccharides 451:465 arg1 polysaccharides 451:465 polysaccharides 451:465 polysaccharides 451:465 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 5 11 theme cork 834:837 arg1 decomposition 839:851 the cork decomposition 830:851 the cork decomposition 830:851 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 7 12 theme non-polar 1068:1076 arg1 extractives 1078:1088 non-polar extractives 1068:1088 non-polar extractives 1068:1088 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 9 13 theme flammable 1388:1396 arg1 gases 1398:1402 more flammable gases 1383:1402 more flammable gases 1383:1402 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 1 14 from L. 275:276 arg1 decomposition 192:204 pyrolysis decomposition 182:204 pyrolysis decomposition 182:204 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 1 14 from L. 275:276 arg1 powder 249:254 a cork oak powder 238:254 a cork oak powder from Quercus suber L. 238:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 1 14 from L. 275:276 arg1 mechanisms 224:233 fire reaction mechanisms 210:233 fire reaction mechanisms 210:233 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 1 15 theme cork 240:243 arg1 powder 249:254 a cork oak powder 238:254 a cork oak powder from Quercus suber L. 238:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 5 16 theme stable 801:806 arg1 residue 808:814 a more thermally stable residue 784:814 a more thermally stable residue at the end of the cork decomposition 784:851 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 1 17 from influence 110:118 arg1 decomposition 192:204 pyrolysis decomposition 182:204 pyrolysis decomposition 182:204 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 1 17 from influence 110:118 arg1 mechanisms 224:233 fire reaction mechanisms 210:233 fire reaction mechanisms 210:233 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 6 18 theme temperature 920:930 arg1 shift 887:891 a shift 885:891 a shift of the onset decomposition temperature to a lower temperature 885:953 Moreover, by removing suberin, a shift of the onset decomposition temperature to a lower temperature was noticed, indicating that suberin plays a major role in enhancing the thermal stability of cork. 37241456 4 19 theme absorbance 495:504 arg1 peaks 506:510 The absorbance peaks 491:510 The absorbance peaks of cork and its individual components 491:548 The absorbance peaks of cork and its individual components were further analyzed by means of ATR-FTIR spectrometry. 37241456 3 20 theme main 374:377 arg1 Suberin 358:364 Suberin 358:364 Suberin 358:364 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 20 theme main 374:377 arg1 component 379:387 the main component 370:387 the main component 370:387 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 1 21 from analysis 94:101 arg1 decomposition 192:204 pyrolysis decomposition 182:204 pyrolysis decomposition 182:204 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 1 21 from analysis 94:101 arg1 mechanisms 224:233 fire reaction mechanisms 210:233 fire reaction mechanisms 210:233 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 6 22 theme thermal 1028:1034 arg1 stability 1036:1044 the thermal stability 1024:1044 the thermal stability of cork 1024:1052 Moreover, by removing suberin, a shift of the onset decomposition temperature to a lower temperature was noticed, indicating that suberin plays a major role in enhancing the thermal stability of cork. 37241456 1 23 theme suberin 136:142 arg1 influence 110:118 the influence 106:118 the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. 106:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 7 24 theme heat 1137:1140 arg1 pHRR 1156:1159 pHRR 1156:1159 pHRR 1156:1159 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 7 24 theme heat 1137:1140 arg1 rate 1150:1153 heat release rate 1137:1153 heat release rate (pHRR) of 365 W/g 1137:1171 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 6 25 theme lower 937:941 arg1 temperature 943:953 a lower temperature 935:953 a lower temperature 935:953 Moreover, by removing suberin, a shift of the onset decomposition temperature to a lower temperature was noticed, indicating that suberin plays a major role in enhancing the thermal stability of cork. 37241456 1 26 theme oak 245:247 arg1 powder 249:254 a cork oak powder 238:254 a cork oak powder from Quercus suber L. 238:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 6 27 theme major 1000:1004 arg1 role 1006:1009 a major role 998:1009 a major role 998:1009 Moreover, by removing suberin, a shift of the onset decomposition temperature to a lower temperature was noticed, indicating that suberin plays a major role in enhancing the thermal stability of cork. 37241456 9 28 theme prominent 1538:1546 arg1 mode 1558:1561 their prominent condensed mode 1532:1561 their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process 1532:1655 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 3 29 theme extractives 478:488 arg1 lignin 436:441 lignin 436:441 lignin 436:441 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 29 theme extractives 478:488 arg1 % 473:473 14% 471:473 14% of extractives 471:488 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 29 theme extractives 478:488 arg1 extractives 478:488 extractives 478:488 extractives 478:488 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 29 theme extractives 478:488 arg1 % 446:446 19% 444:446 19% of polysaccharides 444:465 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 29 theme extractives 478:488 arg1 % 431:431 24% 429:431 24% of lignin 429:441 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 29 theme extractives 478:488 arg1 polysaccharides 451:465 polysaccharides 451:465 polysaccharides 451:465 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 9 30 theme heat 1603:1606 arg1 processes 1617:1625 the mass and heat transfer processes 1590:1625 processes 1617:1625 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 1 31 theme lignocellulosic 148:162 arg1 components 164:173 lignocellulosic components 148:173 lignocellulosic components 148:173 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 9 32 theme action 1566:1571 arg1 mode 1558:1561 their prominent condensed mode 1532:1561 their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process 1532:1655 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 1 33 theme powder 249:254 arg1 decomposition 192:204 pyrolysis decomposition 182:204 pyrolysis decomposition 182:204 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 1 33 theme powder 249:254 arg1 mechanisms 224:233 fire reaction mechanisms 210:233 fire reaction mechanisms 210:233 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 9 34 theme mentioned 1482:1490 arg1 components 1492:1501 the mentioned components 1478:1501 the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process 1478:1655 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 1 35 theme components 164:173 arg1 influence 110:118 the influence 106:118 the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. 106:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 5 36 from formation 771:779 arg1 end 823:825 the end 819:825 the end of the cork decomposition 819:851 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 7 37 dep showed 1090:1095 arg1 analyzed 1173:1180 analyzed 1173:1180 showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC) 1090:1233 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 6 38 theme cork 1049:1052 arg1 stability 1036:1044 the thermal stability 1024:1044 the thermal stability of cork 1024:1052 Moreover, by removing suberin, a shift of the onset decomposition temperature to a lower temperature was noticed, indicating that suberin plays a major role in enhancing the thermal stability of cork. 37241456 3 39 theme lignin 436:441 arg1 lignin 436:441 lignin 436:441 lignin 436:441 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 39 theme lignin 436:441 arg1 % 473:473 14% 471:473 14% of extractives 471:488 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 39 theme lignin 436:441 arg1 extractives 478:488 extractives 478:488 extractives 478:488 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 39 theme lignin 436:441 arg1 % 446:446 19% 444:446 19% of polysaccharides 444:465 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 39 theme lignin 436:441 arg1 % 431:431 24% 429:431 24% of lignin 429:441 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 39 theme lignin 436:441 arg1 polysaccharides 451:465 polysaccharides 451:465 polysaccharides 451:465 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 4 40 theme individual 528:537 arg1 components 539:548 its individual components 524:548 its individual components 524:548 The absorbance peaks of cork and its individual components were further analyzed by means of ATR-FTIR spectrometry. 37241456 0 41 theme Thermal 25:31 arg1 Stability 33:41 Thermal Stability 25:41 Thermal Stability 25:41 The Components' Roles in Thermal Stability and Flammability of Cork Powder. 37241456 1 42 theme Quercus 261:267 arg1 L. 275:276 Quercus suber L. 261:276 Quercus suber L. 261:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 1 43 from mechanisms 224:233 arg1 analysis 94:101 an analysis 91:101 an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. 91:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 1 43 from mechanisms 224:233 arg1 L. 275:276 Quercus suber L. 261:276 Quercus suber L. 261:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 7 44 theme W/g 1169:1171 arg1 pHRR 1156:1159 pHRR 1156:1159 pHRR 1156:1159 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 7 44 theme W/g 1169:1171 arg1 rate 1150:1153 heat release rate 1137:1153 heat release rate (pHRR) of 365 W/g 1137:1171 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 6 45 theme decomposition 906:918 arg1 temperature 920:930 the onset decomposition temperature 896:930 the onset decomposition temperature 896:930 Moreover, by removing suberin, a shift of the onset decomposition temperature to a lower temperature was noticed, indicating that suberin plays a major role in enhancing the thermal stability of cork. 37241456 7 46 dep calorimetry 1217:1227 arg1 means 1185:1189 means 1185:1189 means 1185:1189 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 1 47 theme suber 269:273 arg1 L. 275:276 Quercus suber L. 261:276 Quercus suber L. 261:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 9 48 theme transfer 1608:1615 arg1 processes 1617:1625 the mass and heat transfer processes 1590:1625 processes 1617:1625 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 1 49 dep decomposition 192:204 arg1 the 178:180 the 178:180 the 178:180 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 5 50 theme residue 808:814 arg1 formation 771:779 the formation 767:779 the formation of a more thermally stable residue at the end of the cork decomposition 767:851 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 1 51 theme pyrolysis 182:190 arg1 decomposition 192:204 pyrolysis decomposition 182:204 pyrolysis decomposition 182:204 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 6 52 theme onset 900:904 arg1 temperature 920:930 the onset decomposition temperature 896:930 the onset decomposition temperature 896:930 Moreover, by removing suberin, a shift of the onset decomposition temperature to a lower temperature was noticed, indicating that suberin plays a major role in enhancing the thermal stability of cork. 37241456 7 53 theme highest 1101:1107 arg1 flammability 1109:1120 the highest flammability 1097:1120 the highest flammability with a peak of heat release rate (pHRR) of 365 W/g 1097:1171 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 9 54 theme due 1525:1527 arg1 HRR 1521:1523 lower HRR 1515:1523 lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process 1515:1655 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 2 55 theme chemical 306:313 arg1 composition 315:325 The summative chemical composition 292:325 The summative chemical composition of cork powder 292:340 The summative chemical composition of cork powder was determined. 37241456 5 56 theme thermal 712:718 arg1 stability 720:728 the thermal stability 708:728 the thermal stability between 200 °C and 300 °C 708:754 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 8 57 theme suberin 1281:1287 arg1 HRR 1273:1275 HRR 1273:1275 HRR 1273:1275 Above 300 °C, the heat release rate (HRR) of suberin was lower than that of polysaccharides or lignin. 37241456 8 57 theme suberin 1281:1287 arg1 rate 1267:1270 the heat release rate 1250:1270 the heat release rate (HRR) of suberin 1250:1287 Above 300 °C, the heat release rate (HRR) of suberin was lower than that of polysaccharides or lignin. 37241456 8 57 theme suberin 1281:1287 arg1 lower 1293:1297 lower 1293:1297 lower 1293:1297 Above 300 °C, the heat release rate (HRR) of suberin was lower than that of polysaccharides or lignin. 37241456 9 58 theme W/g 1423:1425 arg1 pHRR 1411:1414 a pHRR 1409:1414 a pHRR of 180 W/g 1409:1425 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 7 59 theme release 1142:1148 arg1 pHRR 1156:1159 pHRR 1156:1159 pHRR 1156:1159 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 7 59 theme release 1142:1148 arg1 rate 1150:1153 heat release rate 1137:1153 heat release rate (pHRR) of 365 W/g 1137:1171 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 2 60 theme summative 296:304 arg1 composition 315:325 The summative chemical composition 292:325 The summative chemical composition of cork powder 292:340 The summative chemical composition of cork powder was determined. 37241456 8 61 theme heat 1254:1257 arg1 HRR 1273:1275 HRR 1273:1275 HRR 1273:1275 Above 300 °C, the heat release rate (HRR) of suberin was lower than that of polysaccharides or lignin. 37241456 8 61 theme heat 1254:1257 arg1 rate 1267:1270 the heat release rate 1250:1270 the heat release rate (HRR) of suberin 1250:1287 Above 300 °C, the heat release rate (HRR) of suberin was lower than that of polysaccharides or lignin. 37241456 8 61 theme heat 1254:1257 arg1 lower 1293:1297 lower 1293:1297 lower 1293:1297 Above 300 °C, the heat release rate (HRR) of suberin was lower than that of polysaccharides or lignin. 37241456 1 62 from decomposition 192:204 arg1 analysis 94:101 an analysis 91:101 an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. 91:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 1 62 from decomposition 192:204 arg1 L. 275:276 Quercus suber L. 261:276 Quercus suber L. 261:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 5 63 from cork 684:687 arg1 removal 656:662 the removal 652:662 the removal of extractives from cork 652:687 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 7 64 theme micro-scale 1194:1204 arg1 MCC 1230:1232 MCC 1230:1232 MCC 1230:1232 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 7 64 theme micro-scale 1194:1204 arg1 calorimetry 1217:1227 micro-scale combustion calorimetry 1194:1227 micro-scale combustion calorimetry (MCC) 1194:1233 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 4 65 theme ATR-FTIR 584:591 arg1 spectrometry 593:604 ATR-FTIR spectrometry 584:604 ATR-FTIR spectrometry 584:604 The absorbance peaks of cork and its individual components were further analyzed by means of ATR-FTIR spectrometry. 37241456 9 66 theme combustion 1638:1647 arg1 process 1649:1655 the combustion process 1634:1655 the combustion process 1634:1655 However, below that temperature it released more flammable gases with a pHRR of 180 W/g, without significant charring ability, contrary to the mentioned components that showed lower HRR due to their prominent condensed mode of action that slowed down the mass and heat transfer processes during the combustion process. 37241456 4 67 theme cork 515:518 arg1 peaks 506:510 The absorbance peaks 491:510 The absorbance peaks of cork and its individual components 491:548 The absorbance peaks of cork and its individual components were further analyzed by means of ATR-FTIR spectrometry. 37241456 5 68 theme Thermogravimetric 607:623 arg1 TGA 635:637 TGA 635:637 TGA 635:637 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 5 68 theme Thermogravimetric 607:623 arg1 analysis 625:632 Thermogravimetric analysis 607:632 Thermogravimetric analysis (TGA) 607:638 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 7 69 theme rate 1150:1153 arg1 peak 1129:1132 a peak 1127:1132 a peak of heat release rate (pHRR) of 365 W/g 1127:1171 Furthermore, non-polar extractives showed the highest flammability with a peak of heat release rate (pHRR) of 365 W/g analyzed by means of micro-scale combustion calorimetry (MCC). 37241456 5 70 theme decomposition 839:851 arg1 end 823:825 the end 819:825 the end of the cork decomposition 819:851 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 2 71 theme cork 330:333 arg1 powder 335:340 cork powder 330:340 cork powder 330:340 The summative chemical composition of cork powder was determined. 37241456 5 72 from end 823:825 arg1 residue 808:814 a more thermally stable residue 784:814 a more thermally stable residue at the end of the cork decomposition 784:851 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 5 72 from end 823:825 arg1 formation 771:779 the formation 767:779 the formation of a more thermally stable residue at the end of the cork decomposition 767:851 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 3 73 theme total 403:407 arg1 weight 409:414 the total weight 399:414 the total weight 399:414 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 8 74 theme release 1259:1265 arg1 HRR 1273:1275 HRR 1273:1275 HRR 1273:1275 Above 300 °C, the heat release rate (HRR) of suberin was lower than that of polysaccharides or lignin. 37241456 8 74 theme release 1259:1265 arg1 rate 1267:1270 the heat release rate 1250:1270 the heat release rate (HRR) of suberin 1250:1287 Above 300 °C, the heat release rate (HRR) of suberin was lower than that of polysaccharides or lignin. 37241456 8 74 theme release 1259:1265 arg1 lower 1293:1297 lower 1293:1297 lower 1293:1297 Above 300 °C, the heat release rate (HRR) of suberin was lower than that of polysaccharides or lignin. 37241456 3 75 theme weight 409:414 arg1 % 394:394 40% 392:394 40% of the total weight 392:414 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 75 theme weight 409:414 arg1 weight 409:414 the total weight 399:414 the total weight 399:414 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 2 76 theme powder 335:340 arg1 composition 315:325 The summative chemical composition 292:325 The summative chemical composition of cork powder 292:340 The summative chemical composition of cork powder was determined. 37241456 1 77 theme fire 210:213 arg1 mechanisms 224:233 fire reaction mechanisms 210:233 fire reaction mechanisms 210:233 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 5 78 theme extractives 667:677 arg1 removal 656:662 the removal 652:662 the removal of extractives from cork 652:687 Thermogravimetric analysis (TGA) showed that the removal of extractives from cork slightly increased the thermal stability between 200 °C and 300 °C and led to the formation of a more thermally stable residue at the end of the cork decomposition. 37241456 0 79 from Roles 16:20 arg1 Flammability 47:58 Flammability 47:58 Flammability 47:58 The Components' Roles in Thermal Stability and Flammability of Cork Powder. 37241456 0 79 from Roles 16:20 arg1 Stability 33:41 Thermal Stability 25:41 Thermal Stability 25:41 The Components' Roles in Thermal Stability and Flammability of Cork Powder. 37241456 4 80 theme components 539:548 arg1 peaks 506:510 The absorbance peaks 491:510 The absorbance peaks of cork and its individual components 491:548 The absorbance peaks of cork and its individual components were further analyzed by means of ATR-FTIR spectrometry. 37241456 3 81 from % 394:394 arg1 Suberin 358:364 Suberin 358:364 Suberin 358:364 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 3 81 from % 394:394 arg1 component 379:387 the main component 370:387 the main component 370:387 Suberin was the main component at 40% of the total weight, followed by 24% of lignin, 19% of polysaccharides and 14% of extractives. 37241456 1 82 theme influence 110:118 arg1 analysis 94:101 an analysis 91:101 an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. 91:276 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 37241456 1 83 theme reaction 215:222 arg1 mechanisms 224:233 fire reaction mechanisms 210:233 fire reaction mechanisms 210:233 In this study, an analysis of the influence of extractives, suberin and lignocellulosic components on the pyrolysis decomposition and fire reaction mechanisms of a cork oak powder from Quercus suber L. is presented. 36913756 10 0 theme metabolism 1541:1550 arg1 activities 1527:1536 the activities 1523:1536 the activities of metabolism of cofactors and vitamins 1523:1576 Moreover, immune stress increased the activities of metabolism of cofactors and vitamins, as well as decreased the ability of energy metabolism and digestive system. 36913756 9 1 theme gut 1267:1269 arg1 microbiota 1271:1280 these gut microbiota 1261:1280 these gut microbiota 1261:1280 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 2 2 theme immune 356:361 arg1 stress 363:368 immune stress 356:368 immune stress 356:368 The present research was designed to investigate the effect of immune stress on the cecal microbiome in broilers. 36913756 11 3 theme correlation 1665:1675 arg1 analysis 1677:1684 Pearson's correlation analysis 1655:1684 Pearson's correlation analysis 1655:1684 Pearson's correlation analysis identified several bacteria were positively correlated with the gene expression while a few of bacteria were negatively correlated with the gene expression. 36913756 11 4 theme bacteria 1781:1788 arg1 few 1774:1776 few 1774:1776 few 1774:1776 Pearson's correlation analysis identified several bacteria were positively correlated with the gene expression while a few of bacteria were negatively correlated with the gene expression. 36913756 5 5 theme 250 779:781 arg1 µg/kg 783:787 µg/kg 783:787 µg/kg 783:787 The model broilers were intraperitoneally injected of 250 µg/kg LPS at 12, 14, 33, and 35 d of age to induce immunological stress. 36913756 4 6 with groups 664:669 arg1 birds 710:714 10 birds 707:714 10 birds per pen 707:722 Eighty broiler chicks were randomly assigned to 2 groups with 4 replicate pens per group and 10 birds per pen. 36913756 4 6 with groups 664:669 arg1 pens 688:691 4 replicate pens 676:691 4 replicate pens per group 676:701 Eighty broiler chicks were randomly assigned to 2 groups with 4 replicate pens per group and 10 birds per pen. 36913756 11 7 theme several 1697:1703 arg1 bacteria 1705:1712 several bacteria 1697:1712 several bacteria 1697:1712 Pearson's correlation analysis identified several bacteria were positively correlated with the gene expression while a few of bacteria were negatively correlated with the gene expression. 36913756 8 8 theme taxonomic 1205:1213 arg1 levels 1215:1220 different taxonomic levels 1195:1220 different taxonomic levels 1195:1220 The results showed that immune stress significantly changed microbiota composition at different taxonomic levels. 36913756 12 9 theme broiler 2035:2041 arg1 chickens 2043:2050 broiler chickens 2035:2050 broiler chickens 2035:2050 The results identified potential microbiota involvement in growth depression mediated by immune stress and provided strategies such as supplement of probiotic for alleviating immune stress in broiler chickens. 36913756 7 10 theme serum 1057:1061 arg1 metabolites 1063:1073 serum metabolites 1057:1073 serum metabolites 1057:1073 Then the Pearson's correlation between gut microbiome and liver transcriptome, between gut microbiome and serum metabolites were calculated using R software. 36913756 1 11 theme broilers 264:271 arg1 liver 255:259 the liver 251:259 the liver of broilers with immune stress 251:290 A previous study identified genes and metabolites associated with amino acid metabolism, glycerophospholipid metabolism, and inflammatory response in the liver of broilers with immune stress. 36913756 0 12 theme immune 86:91 arg1 stress 93:98 immune stress 86:98 immune stress 86:98 Changed cecal microbiota involved in growth depression of broiler chickens induced by immune stress. 36913756 6 13 theme Cecal 856:860 arg1 contents 862:869 Cecal contents 856:869 Cecal contents 856:869 Cecal contents were taken after the experiment and kept at -80°C for 16S rDNA gene sequencing. 36913756 2 14 from effect 346:351 arg1 microbiome 383:392 the cecal microbiome 373:392 the cecal microbiome in broilers 373:404 The present research was designed to investigate the effect of immune stress on the cecal microbiome in broilers. 36913756 12 15 theme growth 1902:1907 arg1 depression 1909:1918 growth depression 1902:1918 growth depression mediated by immune stress 1902:1944 The results identified potential microbiota involvement in growth depression mediated by immune stress and provided strategies such as supplement of probiotic for alleviating immune stress in broiler chickens. 36913756 6 16 theme rDNA 929:932 arg1 sequencing 939:948 rDNA gene sequencing 929:948 rDNA gene sequencing 929:948 Cecal contents were taken after the experiment and kept at -80°C for 16S rDNA gene sequencing. 36913756 10 17 theme vitamins 1569:1576 arg1 metabolism 1541:1550 metabolism 1541:1550 metabolism of cofactors and vitamins 1541:1576 Moreover, immune stress increased the activities of metabolism of cofactors and vitamins, as well as decreased the ability of energy metabolism and digestive system. 36913756 9 18 theme vancomycin 1459:1468 arg1 antibiotics 1476:1486 vancomycin group antibiotics 1459:1486 vancomycin group antibiotics 1459:1486 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 10 19 theme system 1647:1652 arg1 ability 1604:1610 the ability 1600:1610 the ability of energy metabolism and digestive system 1600:1652 Moreover, immune stress increased the activities of metabolism of cofactors and vitamins, as well as decreased the ability of energy metabolism and digestive system. 36913756 1 20 theme amino 167:171 arg1 metabolism 178:187 amino acid metabolism 167:187 amino acid metabolism 167:187 A previous study identified genes and metabolites associated with amino acid metabolism, glycerophospholipid metabolism, and inflammatory response in the liver of broilers with immune stress. 36913756 5 21 theme µg/kg 783:787 arg1 LPS 789:791 250 µg/kg LPS 779:791 250 µg/kg LPS 779:791 The model broilers were intraperitoneally injected of 250 µg/kg LPS at 12, 14, 33, and 35 d of age to induce immunological stress. 36913756 3 22 theme serum 537:541 arg1 metabolites 543:553 serum metabolites 537:553 serum metabolites 537:553 In addition, the correlation between altered microbiota and liver gene expression, the correlation between altered microbiota and serum metabolites were compared using the Spearman correlation coefficients. 36913756 1 23 theme acid 173:176 arg1 metabolism 178:187 amino acid metabolism 167:187 amino acid metabolism 167:187 A previous study identified genes and metabolites associated with amino acid metabolism, glycerophospholipid metabolism, and inflammatory response in the liver of broilers with immune stress. 36913756 0 24 theme cecal 8:12 arg1 microbiota 14:23 Changed cecal microbiota 0:23 Changed cecal microbiota 0:23 Changed cecal microbiota involved in growth depression of broiler chickens induced by immune stress. 36913756 12 25 from involvement 1887:1897 arg1 depression 1909:1918 growth depression 1902:1918 growth depression mediated by immune stress 1902:1944 The results identified potential microbiota involvement in growth depression mediated by immune stress and provided strategies such as supplement of probiotic for alleviating immune stress in broiler chickens. 36913756 10 26 theme cofactors 1555:1563 arg1 metabolism 1541:1550 metabolism 1541:1550 metabolism of cofactors and vitamins 1541:1576 Moreover, immune stress increased the activities of metabolism of cofactors and vitamins, as well as decreased the ability of energy metabolism and digestive system. 36913756 2 27 theme cecal 377:381 arg1 microbiome 383:392 the cecal microbiome 373:392 the cecal microbiome in broilers 373:404 The present research was designed to investigate the effect of immune stress on the cecal microbiome in broilers. 36913756 0 28 theme Changed 0:6 arg1 microbiota 14:23 Changed cecal microbiota 0:23 Changed cecal microbiota 0:23 Changed cecal microbiota involved in growth depression of broiler chickens induced by immune stress. 36913756 1 29 theme immune 278:283 arg1 stress 285:290 immune stress 278:290 immune stress 278:290 A previous study identified genes and metabolites associated with amino acid metabolism, glycerophospholipid metabolism, and inflammatory response in the liver of broilers with immune stress. 36913756 7 30 theme gut 1038:1040 arg1 microbiome 1042:1051 gut microbiome 1038:1051 gut microbiome 1038:1051 Then the Pearson's correlation between gut microbiome and liver transcriptome, between gut microbiome and serum metabolites were calculated using R software. 36913756 3 31 theme Spearman 579:586 arg1 coefficients 600:611 the Spearman correlation coefficients 575:611 the Spearman correlation coefficients 575:611 In addition, the correlation between altered microbiota and liver gene expression, the correlation between altered microbiota and serum metabolites were compared using the Spearman correlation coefficients. 36913756 9 32 theme ansamycins 1322:1331 arg1 valine 1394:1399 valine 1394:1399 valine 1394:1399 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 32 theme ansamycins 1322:1331 arg1 biosynthesis 1426:1437 isoleucine biosynthesis 1415:1437 isoleucine biosynthesis 1415:1437 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 32 theme ansamycins 1322:1331 arg1 degradation 1341:1351 glycan degradation 1334:1351 glycan degradation 1334:1351 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 32 theme ansamycins 1322:1331 arg1 biosynthesis 1306:1317 biosynthesis 1306:1317 biosynthesis of ansamycins 1306:1331 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 32 theme ansamycins 1322:1331 arg1 biosynthesis 1443:1454 biosynthesis 1443:1454 biosynthesis 1443:1454 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 32 theme ansamycins 1322:1331 arg1 D-glutamine 1354:1364 D-glutamine 1354:1364 D-glutamine 1354:1364 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 32 theme ansamycins 1322:1331 arg1 leucine 1402:1408 leucine 1402:1408 leucine 1402:1408 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 32 theme ansamycins 1322:1331 arg1 metabolism 1382:1391 D-glutamate metabolism 1370:1391 D-glutamate metabolism 1370:1391 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 10 33 theme immune 1499:1504 arg1 stress 1506:1511 immune stress 1499:1511 immune stress 1499:1511 Moreover, immune stress increased the activities of metabolism of cofactors and vitamins, as well as decreased the ability of energy metabolism and digestive system. 36913756 9 34 theme isoleucine 1415:1424 arg1 biosynthesis 1426:1437 isoleucine biosynthesis 1415:1437 isoleucine biosynthesis 1415:1437 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 11 35 dep identified 1686:1695 arg1 correlated 1730:1739 correlated 1730:1739 correlated 1730:1739 Pearson's correlation analysis identified several bacteria were positively correlated with the gene expression while a few of bacteria were negatively correlated with the gene expression. 36913756 1 36 theme glycerophospholipid 190:208 arg1 metabolism 210:219 glycerophospholipid metabolism 190:219 glycerophospholipid metabolism 190:219 A previous study identified genes and metabolites associated with amino acid metabolism, glycerophospholipid metabolism, and inflammatory response in the liver of broilers with immune stress. 36913756 12 37 theme immune 2018:2023 arg1 stress 2025:2030 immune stress 2018:2030 immune stress 2018:2030 The results identified potential microbiota involvement in growth depression mediated by immune stress and provided strategies such as supplement of probiotic for alleviating immune stress in broiler chickens. 36913756 2 38 theme present 297:303 arg1 research 305:312 The present research 293:312 The present research 293:312 The present research was designed to investigate the effect of immune stress on the cecal microbiome in broilers. 36913756 3 39 theme liver 467:471 arg1 expression 478:487 altered microbiota and liver gene expression 444:487 expression 478:487 In addition, the correlation between altered microbiota and liver gene expression, the correlation between altered microbiota and serum metabolites were compared using the Spearman correlation coefficients. 36913756 0 40 theme growth 37:42 arg1 depression 44:53 growth depression 37:53 growth depression of broiler chickens induced by immune stress 37:98 Changed cecal microbiota involved in growth depression of broiler chickens induced by immune stress. 36913756 9 41 theme glycan 1334:1339 arg1 degradation 1341:1351 glycan degradation 1334:1351 glycan degradation 1334:1351 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 42 theme group 1470:1474 arg1 antibiotics 1476:1486 vancomycin group antibiotics 1459:1486 vancomycin group antibiotics 1459:1486 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 3 43 theme altered 444:450 arg1 microbiota 452:461 altered microbiota and liver gene expression 444:487 microbiota 452:461 In addition, the correlation between altered microbiota and liver gene expression, the correlation between altered microbiota and serum metabolites were compared using the Spearman correlation coefficients. 36913756 8 44 theme microbiota 1169:1178 arg1 composition 1180:1190 microbiota composition 1169:1190 microbiota composition 1169:1190 The results showed that immune stress significantly changed microbiota composition at different taxonomic levels. 36913756 7 45 theme liver 1009:1013 arg1 transcriptome 1015:1027 liver transcriptome 1009:1027 liver transcriptome 1009:1027 Then the Pearson's correlation between gut microbiome and liver transcriptome, between gut microbiome and serum metabolites were calculated using R software. 36913756 1 46 with broilers 264:271 arg1 stress 285:290 immune stress 278:290 immune stress 278:290 A previous study identified genes and metabolites associated with amino acid metabolism, glycerophospholipid metabolism, and inflammatory response in the liver of broilers with immune stress. 36913756 9 47 theme antibiotics 1476:1486 arg1 valine 1394:1399 valine 1394:1399 valine 1394:1399 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 47 theme antibiotics 1476:1486 arg1 biosynthesis 1426:1437 isoleucine biosynthesis 1415:1437 isoleucine biosynthesis 1415:1437 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 47 theme antibiotics 1476:1486 arg1 degradation 1341:1351 glycan degradation 1334:1351 glycan degradation 1334:1351 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 47 theme antibiotics 1476:1486 arg1 biosynthesis 1306:1317 biosynthesis 1306:1317 biosynthesis of ansamycins 1306:1331 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 47 theme antibiotics 1476:1486 arg1 biosynthesis 1443:1454 biosynthesis 1443:1454 biosynthesis 1443:1454 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 47 theme antibiotics 1476:1486 arg1 D-glutamine 1354:1364 D-glutamine 1354:1364 D-glutamine 1354:1364 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 47 theme antibiotics 1476:1486 arg1 leucine 1402:1408 leucine 1402:1408 leucine 1402:1408 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 9 47 theme antibiotics 1476:1486 arg1 metabolism 1382:1391 D-glutamate metabolism 1370:1391 D-glutamate metabolism 1370:1391 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 8 48 theme different 1195:1203 arg1 levels 1215:1220 different taxonomic levels 1195:1220 different taxonomic levels 1195:1220 The results showed that immune stress significantly changed microbiota composition at different taxonomic levels. 36913756 5 49 theme immunological 834:846 arg1 stress 848:853 immunological stress 834:853 immunological stress 834:853 The model broilers were intraperitoneally injected of 250 µg/kg LPS at 12, 14, 33, and 35 d of age to induce immunological stress. 36913756 7 50 theme gut 990:992 arg1 microbiome 994:1003 gut microbiome 990:1003 gut microbiome 990:1003 Then the Pearson's correlation between gut microbiome and liver transcriptome, between gut microbiome and serum metabolites were calculated using R software. 36913756 9 51 theme KEGG 1223:1226 arg1 pathways 1228:1235 KEGG pathways 1223:1235 KEGG pathways analysis 1223:1244 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 3 52 theme correlation 588:598 arg1 coefficients 600:611 the Spearman correlation coefficients 575:611 the Spearman correlation coefficients 575:611 In addition, the correlation between altered microbiota and liver gene expression, the correlation between altered microbiota and serum metabolites were compared using the Spearman correlation coefficients. 36913756 12 53 theme microbiota 1876:1885 arg1 involvement 1887:1897 potential microbiota involvement 1866:1897 potential microbiota involvement in growth depression mediated by immune stress 1866:1944 The results identified potential microbiota involvement in growth depression mediated by immune stress and provided strategies such as supplement of probiotic for alleviating immune stress in broiler chickens. 36913756 1 54 theme previous 103:110 arg1 study 112:116 A previous study 101:116 A previous study 101:116 A previous study identified genes and metabolites associated with amino acid metabolism, glycerophospholipid metabolism, and inflammatory response in the liver of broilers with immune stress. 36913756 7 55 theme R 1097:1097 arg1 software 1099:1106 R software 1097:1106 R software 1097:1106 Then the Pearson's correlation between gut microbiome and liver transcriptome, between gut microbiome and serum metabolites were calculated using R software. 36913756 9 56 theme pathways 1228:1235 arg1 analysis 1237:1244 KEGG pathways analysis 1223:1244 KEGG pathways analysis 1223:1244 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 4 57 theme Eighty 614:619 arg1 chicks 629:634 Eighty broiler chicks 614:634 Eighty broiler chicks 614:634 Eighty broiler chicks were randomly assigned to 2 groups with 4 replicate pens per group and 10 birds per pen. 36913756 6 58 theme gene 934:937 arg1 sequencing 939:948 rDNA gene sequencing 929:948 rDNA gene sequencing 929:948 Cecal contents were taken after the experiment and kept at -80°C for 16S rDNA gene sequencing. 36913756 12 59 theme probiotic 1992:2000 arg1 supplement 1978:1987 supplement 1978:1987 supplement of probiotic 1978:2000 The results identified potential microbiota involvement in growth depression mediated by immune stress and provided strategies such as supplement of probiotic for alleviating immune stress in broiler chickens. 36913756 10 60 theme metabolism 1622:1631 arg1 ability 1604:1610 the ability 1600:1610 the ability of energy metabolism and digestive system 1600:1652 Moreover, immune stress increased the activities of metabolism of cofactors and vitamins, as well as decreased the ability of energy metabolism and digestive system. 36913756 12 61 theme immune 1932:1937 arg1 stress 1939:1944 immune stress 1932:1944 immune stress 1932:1944 The results identified potential microbiota involvement in growth depression mediated by immune stress and provided strategies such as supplement of probiotic for alleviating immune stress in broiler chickens. 36913756 4 62 dep pens 688:691 arg1 replicate 678:686 replicate 678:686 replicate 678:686 Eighty broiler chicks were randomly assigned to 2 groups with 4 replicate pens per group and 10 birds per pen. 36913756 2 63 from microbiome 383:392 arg1 broilers 397:404 broilers 397:404 broilers 397:404 The present research was designed to investigate the effect of immune stress on the cecal microbiome in broilers. 36913756 3 64 theme gene 473:476 arg1 expression 478:487 altered microbiota and liver gene expression 444:487 expression 478:487 In addition, the correlation between altered microbiota and liver gene expression, the correlation between altered microbiota and serum metabolites were compared using the Spearman correlation coefficients. 36913756 9 65 theme D-glutamate 1370:1380 arg1 metabolism 1382:1391 D-glutamate metabolism 1370:1391 D-glutamate metabolism 1370:1391 KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. 36913756 1 66 theme inflammatory 226:237 arg1 response 239:246 inflammatory response 226:246 inflammatory response 226:246 A previous study identified genes and metabolites associated with amino acid metabolism, glycerophospholipid metabolism, and inflammatory response in the liver of broilers with immune stress. 36913756 12 67 theme potential 1866:1874 arg1 involvement 1887:1897 potential microbiota involvement 1866:1897 potential microbiota involvement in growth depression mediated by immune stress 1866:1944 The results identified potential microbiota involvement in growth depression mediated by immune stress and provided strategies such as supplement of probiotic for alleviating immune stress in broiler chickens. 36913756 10 68 theme digestive 1637:1645 arg1 system 1647:1652 digestive system 1637:1652 digestive system 1637:1652 Moreover, immune stress increased the activities of metabolism of cofactors and vitamins, as well as decreased the ability of energy metabolism and digestive system. 36913756 8 69 theme immune 1133:1138 arg1 stress 1140:1145 immune stress 1133:1145 immune stress 1133:1145 The results showed that immune stress significantly changed microbiota composition at different taxonomic levels. 36913756 11 70 theme gene 1826:1829 arg1 expression 1831:1840 the gene expression 1822:1840 the gene expression 1822:1840 Pearson's correlation analysis identified several bacteria were positively correlated with the gene expression while a few of bacteria were negatively correlated with the gene expression. 36913756 4 71 theme broiler 621:627 arg1 chicks 629:634 Eighty broiler chicks 614:634 Eighty broiler chicks 614:634 Eighty broiler chicks were randomly assigned to 2 groups with 4 replicate pens per group and 10 birds per pen. 36913756 0 72 theme chickens 66:73 arg1 depression 44:53 growth depression 37:53 growth depression of broiler chickens induced by immune stress 37:98 Changed cecal microbiota involved in growth depression of broiler chickens induced by immune stress. 36913756 3 73 theme altered 514:520 arg1 microbiota 522:531 altered microbiota 514:531 altered microbiota 514:531 In addition, the correlation between altered microbiota and liver gene expression, the correlation between altered microbiota and serum metabolites were compared using the Spearman correlation coefficients. 36913756 5 74 theme age 820:822 arg1 d 815:815 12, 14, 33, and 35 d 796:815 12, 14, 33, and 35 d of age to induce immunological stress 796:853 The model broilers were intraperitoneally injected of 250 µg/kg LPS at 12, 14, 33, and 35 d of age to induce immunological stress. 36913756 11 75 theme gene 1750:1753 arg1 expression 1755:1764 the gene expression 1746:1764 the gene expression 1746:1764 Pearson's correlation analysis identified several bacteria were positively correlated with the gene expression while a few of bacteria were negatively correlated with the gene expression. 36913756 0 76 theme broiler 58:64 arg1 chickens 66:73 broiler chickens 58:73 broiler chickens induced by immune stress 58:98 Changed cecal microbiota involved in growth depression of broiler chickens induced by immune stress. 36913756 2 77 theme stress 363:368 arg1 effect 346:351 the effect 342:351 the effect of immune stress on the cecal microbiome in broilers 342:404 The present research was designed to investigate the effect of immune stress on the cecal microbiome in broilers. 36913756 10 78 theme energy 1615:1620 arg1 metabolism 1622:1631 energy metabolism 1615:1631 energy metabolism 1615:1631 Moreover, immune stress increased the activities of metabolism of cofactors and vitamins, as well as decreased the ability of energy metabolism and digestive system. 36913756 5 79 theme model 729:733 arg1 broilers 735:742 The model broilers 725:742 The model broilers 725:742 The model broilers were intraperitoneally injected of 250 µg/kg LPS at 12, 14, 33, and 35 d of age to induce immunological stress. 36828168 10 0 theme STC 1488:1490 arg1 effects 1477:1483 the potent anti-obesity effects 1453:1483 the potent anti-obesity effects 1453:1483 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 6 1 dep weight 893:898 arg1 mass 931:934 mass 931:934 mass 931:934 Oral administration of STC, STCF1, and STCF3 significantly reduced body weight and white adipose tissue (WAT) mass. 36828168 8 2 theme serum 1134:1138 arg1 levels 1148:1153 serum insulin levels 1134:1153 serum insulin levels 1134:1153 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 6 3 theme body 888:891 arg1 weight 893:898 body weight 888:898 body weight 888:898 Oral administration of STC, STCF1, and STCF3 significantly reduced body weight and white adipose tissue (WAT) mass. 36828168 10 4 theme STCF3 1504:1508 arg1 effects 1477:1483 the potent anti-obesity effects 1453:1483 the potent anti-obesity effects 1453:1483 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 0 5 theme diet-induced 196:207 arg1 obesity 209:215 in vivo high-fat diet-induced obesity 179:215 in vivo high-fat diet-induced obesity 179:215 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 3 6 theme anti-obesity 564:575 arg1 effects 577:583 anti-obesity effects 564:583 anti-obesity effects 564:583 We investigated their proximate composition, and anti-obesity effects in vitro and in vivo. 36828168 4 7 theme PA-treated 683:692 arg1 3T3-L1 694:699 PA-treated 3T3-L1 and HepG2 cells 683:715 3T3-L1 694:699 STC and STCFs all significantly reduced intracellular lipid accumulation in PA-treated 3T3-L1 and HepG2 cells. 36828168 1 8 attach derived 316:322 arg1 thunbergii 339:348 Sargassum thunbergii 329:348 Sargassum thunbergii 329:348 This study investigated the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii in vitro and in vivo. 36828168 1 8 attach derived 316:322 arg2 compounds 306:314 compounds 306:314 compounds derived from Sargassum thunbergii 306:348 This study investigated the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii in vitro and in vivo. 36828168 9 9 from proteins 1287:1294 arg1 tissue 1318:1323 epididymal adipose tissue 1299:1323 epididymal adipose tissue 1299:1323 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 9 9 from proteins 1287:1294 arg1 tissues 1365:1371 liver tissues 1359:1371 liver tissues 1359:1371 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 4 10 theme intracellular 647:659 arg1 accumulation 667:678 intracellular lipid accumulation 647:678 intracellular lipid accumulation 647:678 STC and STCFs all significantly reduced intracellular lipid accumulation in PA-treated 3T3-L1 and HepG2 cells. 36828168 0 11 theme in 143:144 arg1 3T3-L1 152:157 in vitro 3T3-L1 and HepG2 cells 143:173 3T3-L1 152:157 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 10 12 theme lipolysis 1551:1559 arg1 regulation 1523:1532 regulation 1523:1532 regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice 1523:1631 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 9 13 theme adipose 1310:1316 arg1 tissue 1318:1323 epididymal adipose tissue 1299:1323 epididymal adipose tissue 1299:1323 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 10 14 theme adipogenesis 1537:1548 arg1 regulation 1523:1532 regulation 1523:1532 regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice 1523:1631 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 0 15 theme HepG2 163:167 arg1 cells 169:173 in vitro 3T3-L1 and HepG2 cells 143:173 cells 169:173 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 6 16 theme adipose 910:916 arg1 tissue 918:923 white adipose tissue 904:923 white adipose tissue (WAT) 904:929 Oral administration of STC, STCF1, and STCF3 significantly reduced body weight and white adipose tissue (WAT) mass. 36828168 7 17 theme lipid 956:960 arg1 levels 962:967 serum lipid levels 950:967 serum lipid levels 950:967 Furthermore, serum lipid levels were significantly decreased. 36828168 0 18 theme ethanol 62:68 arg1 precipitation 70:82 step gradient ethanol precipitation 48:82 step gradient ethanol precipitation 48:82 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 5 19 theme fat 782:784 arg1 HFD 792:794 HFD 792:794 HFD 792:794 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 5 19 theme fat 782:784 arg1 diet 786:789 high fat diet 777:789 high fat diet (HFD) 777:795 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 9 20 theme adipogenesis 1249:1260 arg1 proteins 1287:1294 the adipogenesis and lipolysis associated proteins 1245:1294 the adipogenesis and lipolysis associated proteins in epididymal adipose tissue 1245:1323 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 0 21 dep in 143:144 arg1 vitro 146:150 vitro 146:150 vitro 146:150 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 9 22 theme lipolysis 1266:1274 arg1 proteins 1287:1294 the adipogenesis and lipolysis associated proteins 1245:1294 the adipogenesis and lipolysis associated proteins in epididymal adipose tissue 1245:1323 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 8 23 theme adipose 1013:1019 arg1 levels 1038:1043 adipose specific hormone levels 1013:1043 adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) 1013:1098 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 23 theme adipose 1013:1019 arg1 factor-21 1080:1088 fibroblast growth factor-21 1062:1088 fibroblast growth factor-21 (FGF-21) 1062:1097 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 23 theme adipose 1013:1019 arg1 adiponectin 1046:1056 adiponectin 1046:1056 adiponectin 1046:1056 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 10 24 theme acid 1576:1579 arg1 oxidation 1581:1589 the fatty acid oxidation 1566:1589 the fatty acid oxidation pathway 1566:1597 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 5 25 theme anti-obesity 753:764 arg1 effects 766:772 profound anti-obesity effects 744:772 profound anti-obesity effects 744:772 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 8 26 theme hormone 1030:1036 arg1 levels 1038:1043 adipose specific hormone levels 1013:1043 adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) 1013:1098 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 26 theme hormone 1030:1036 arg1 factor-21 1080:1088 fibroblast growth factor-21 1062:1088 fibroblast growth factor-21 (FGF-21) 1062:1097 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 26 theme hormone 1030:1036 arg1 adiponectin 1046:1056 adiponectin 1046:1056 adiponectin 1046:1056 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 0 27 dep anti-obesity 103:114 arg1 3T3-L1 152:157 in vitro 3T3-L1 and HepG2 cells 143:173 3T3-L1 152:157 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 0 27 dep anti-obesity 103:114 arg1 cells 169:173 in vitro 3T3-L1 and HepG2 cells 143:173 cells 169:173 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 0 27 dep anti-obesity 103:114 arg1 mice 217:220 mice 217:220 mice 217:220 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 5 28 theme obesity 801:807 arg1 mice 815:818 high fat diet (HFD)-fed obesity model mice 777:818 high fat diet (HFD)-fed obesity model mice 777:818 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 9 29 theme epididymal 1299:1308 arg1 tissue 1318:1323 epididymal adipose tissue 1299:1323 epididymal adipose tissue 1299:1323 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 2 30 theme fractional 460:469 arg1 precipitates 479:490 three fractional ethanol precipitates 454:490 three fractional ethanol precipitates (STCF1, STCF2, STCF3) 454:512 We prepared a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3). 36828168 10 31 theme HFD-treated 1602:1612 arg1 mice 1628:1631 HFD-treated obesity model mice 1602:1631 HFD-treated obesity model mice 1602:1631 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 0 32 theme Sargassum 14:22 arg1 thunbergii 24:33 Sargassum thunbergii 14:33 Sargassum thunbergii obtained via step gradient ethanol precipitation 14:82 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 10 33 theme pathway 1591:1597 arg1 regulation 1523:1532 regulation 1523:1532 regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice 1523:1631 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 8 34 theme STCF3 1194:1198 arg1 treatment 1200:1208 STCF3 treatment 1194:1208 STCF3 treatment 1194:1208 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 1 35 theme Sargassum 329:337 arg1 thunbergii 339:348 Sargassum thunbergii 329:348 Sargassum thunbergii 329:348 This study investigated the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii in vitro and in vivo. 36828168 8 36 theme growth 1073:1078 arg1 FGF-21 1091:1096 FGF-21 1091:1096 FGF-21 1091:1096 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 36 theme growth 1073:1078 arg1 factor-21 1080:1088 fibroblast growth factor-21 1062:1088 fibroblast growth factor-21 (FGF-21) 1062:1097 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 36 theme growth 1073:1078 arg1 levels 1038:1043 adipose specific hormone levels 1013:1043 adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) 1013:1098 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 0 37 theme step 48:51 arg1 precipitation 70:82 step gradient ethanol precipitation 48:82 step gradient ethanol precipitation 48:82 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 9 38 theme fatty 1335:1339 arg1 oxidation 1346:1354 free fatty acid oxidation 1330:1354 free fatty acid oxidation in liver tissues 1330:1371 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 2 39 from thunbergii 433:442 arg1 hydrolysate 406:416 a Celluclast-assisted hydrolysate 384:416 a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3) 384:512 We prepared a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3). 36828168 10 40 theme potent 1457:1462 arg1 effects 1477:1483 the potent anti-obesity effects 1453:1483 the potent anti-obesity effects 1453:1483 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 10 41 theme model 1622:1626 arg1 mice 1628:1631 HFD-treated obesity model mice 1602:1631 HFD-treated obesity model mice 1602:1631 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 6 42 theme Oral 821:824 arg1 administration 826:839 Oral administration 821:839 Oral administration of STC, STCF1, and STCF3 821:864 Oral administration of STC, STCF1, and STCF3 significantly reduced body weight and white adipose tissue (WAT) mass. 36828168 10 43 theme STCF1 1493:1497 arg1 effects 1477:1483 the potent anti-obesity effects 1453:1483 the potent anti-obesity effects 1453:1483 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 10 44 theme oxidation 1581:1589 arg1 pathway 1591:1597 the fatty acid oxidation pathway 1566:1597 the fatty acid oxidation pathway 1566:1597 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 2 45 theme Celluclast-assisted 386:404 arg1 hydrolysate 406:416 a Celluclast-assisted hydrolysate 384:416 a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3) 384:512 We prepared a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3). 36828168 9 46 theme liver 1359:1363 arg1 tissues 1365:1371 liver tissues 1359:1371 liver tissues 1359:1371 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 6 47 theme white 904:908 arg1 tissue 918:923 white adipose tissue 904:923 white adipose tissue (WAT) 904:929 Oral administration of STC, STCF1, and STCF3 significantly reduced body weight and white adipose tissue (WAT) mass. 36828168 8 48 dep levels 1038:1043 arg1 levels 1038:1043 adipose specific hormone levels 1013:1043 adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) 1013:1098 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 48 dep levels 1038:1043 arg1 FGF-21 1091:1096 FGF-21 1091:1096 FGF-21 1091:1096 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 48 dep levels 1038:1043 arg1 factor-21 1080:1088 fibroblast growth factor-21 1062:1088 fibroblast growth factor-21 (FGF-21) 1062:1097 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 48 dep levels 1038:1043 arg1 adiponectin 1046:1056 adiponectin 1046:1056 adiponectin 1046:1056 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 5 49 theme high 777:780 arg1 HFD 792:794 HFD 792:794 HFD 792:794 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 5 49 theme high 777:780 arg1 diet 786:789 high fat diet 777:789 high fat diet (HFD) 777:795 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 0 50 theme high-fat 187:194 arg1 obesity 209:215 in vivo high-fat diet-induced obesity 179:215 in vivo high-fat diet-induced obesity 179:215 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 1 51 theme inhibitory 267:276 arg1 effects 295:301 the potential lipid inhibitory and anti-obesity effects 247:301 the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii 247:348 This study investigated the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii in vitro and in vivo. 36828168 10 52 from regulation 1523:1532 arg1 mice 1628:1631 HFD-treated obesity model mice 1602:1631 HFD-treated obesity model mice 1602:1631 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 1 53 theme anti-obesity 282:293 arg1 effects 295:301 the potential lipid inhibitory and anti-obesity effects 247:301 the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii 247:348 This study investigated the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii in vitro and in vivo. 36828168 8 54 theme insulin 1140:1146 arg1 levels 1148:1153 serum insulin levels 1134:1153 serum insulin levels 1134:1153 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 6 55 theme STCF3 860:864 arg1 administration 826:839 Oral administration 821:839 Oral administration of STC, STCF1, and STCF3 821:864 Oral administration of STC, STCF1, and STCF3 significantly reduced body weight and white adipose tissue (WAT) mass. 36828168 4 56 theme lipid 661:665 arg1 accumulation 667:678 intracellular lipid accumulation 647:678 intracellular lipid accumulation 647:678 STC and STCFs all significantly reduced intracellular lipid accumulation in PA-treated 3T3-L1 and HepG2 cells. 36828168 0 57 dep in 179:180 arg1 vivo 182:185 vivo 182:185 vivo 182:185 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 0 58 theme in 179:180 arg1 obesity 209:215 in vivo high-fat diet-induced obesity 179:215 in vivo high-fat diet-induced obesity 179:215 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 9 59 theme mechanistic 1213:1223 arg1 study 1225:1229 A mechanistic study 1211:1229 A mechanistic study 1211:1229 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 0 60 from thunbergii 24:33 arg1 Fucoidan 0:7 Fucoidan 0:7 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation 0:82 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 4 61 theme HepG2 705:709 arg1 cells 711:715 PA-treated 3T3-L1 and HepG2 cells 683:715 cells 711:715 STC and STCFs all significantly reduced intracellular lipid accumulation in PA-treated 3T3-L1 and HepG2 cells. 36828168 0 62 theme potential 93:101 arg1 anti-obesity 103:114 potential anti-obesity 93:114 potential anti-obesity 93:114 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 7 63 theme serum 950:954 arg1 levels 962:967 serum lipid levels 950:967 serum lipid levels 950:967 Furthermore, serum lipid levels were significantly decreased. 36828168 2 64 from precipitates 479:490 arg1 hydrolysate 406:416 a Celluclast-assisted hydrolysate 384:416 a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3) 384:512 We prepared a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3). 36828168 8 65 theme specific 1021:1028 arg1 levels 1038:1043 adipose specific hormone levels 1013:1043 adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) 1013:1098 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 65 theme specific 1021:1028 arg1 factor-21 1080:1088 fibroblast growth factor-21 1062:1088 fibroblast growth factor-21 (FGF-21) 1062:1097 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 65 theme specific 1021:1028 arg1 adiponectin 1046:1056 adiponectin 1046:1056 adiponectin 1046:1056 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 5 66 theme profound 744:751 arg1 effects 766:772 profound anti-obesity effects 744:772 profound anti-obesity effects 744:772 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 9 67 theme associated 1276:1285 arg1 proteins 1287:1294 the adipogenesis and lipolysis associated proteins 1245:1294 the adipogenesis and lipolysis associated proteins in epididymal adipose tissue 1245:1323 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 5 68 contain had 740:742 arg1 STCF1 723:727 STCF1 723:727 STCF1 723:727 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 5 68 contain had 740:742 arg1 STCF3 734:738 STCF3 734:738 STCF3 734:738 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 5 68 contain had 740:742 arg1 STC 718:720 STC 718:720 STC 718:720 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 5 68 contain had 740:742 arg2 effects 766:772 profound anti-obesity effects 744:772 profound anti-obesity effects 744:772 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 2 69 theme Sargassum 423:431 arg1 STC 445:447 STC 445:447 STC 445:447 We prepared a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3). 36828168 2 69 theme Sargassum 423:431 arg1 thunbergii 433:442 Sargassum thunbergii 423:442 Sargassum thunbergii (STC) 423:448 We prepared a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3). 36828168 5 70 theme -fed 796:799 arg1 mice 815:818 high fat diet (HFD)-fed obesity model mice 777:818 high fat diet (HFD)-fed obesity model mice 777:818 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 2 71 dep precipitates 479:490 arg1 STCF1 493:497 STCF1 493:497 STCF1 493:497 We prepared a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3). 36828168 2 71 dep precipitates 479:490 arg1 STCF3 507:511 STCF3 507:511 STCF3 507:511 We prepared a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3). 36828168 2 71 dep precipitates 479:490 arg1 STCF2 500:504 STCF2 500:504 STCF2 500:504 We prepared a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3). 36828168 2 72 theme ethanol 471:477 arg1 precipitates 479:490 three fractional ethanol precipitates 454:490 three fractional ethanol precipitates (STCF1, STCF2, STCF3) 454:512 We prepared a Celluclast-assisted hydrolysate from Sargassum thunbergii (STC) and three fractional ethanol precipitates (STCF1, STCF2, STCF3). 36828168 5 73 theme model 809:813 arg1 mice 815:818 high fat diet (HFD)-fed obesity model mice 777:818 high fat diet (HFD)-fed obesity model mice 777:818 STC, STCF1, and STCF3 had profound anti-obesity effects on high fat diet (HFD)-fed obesity model mice. 36828168 1 74 theme compounds 306:314 arg1 effects 295:301 the potential lipid inhibitory and anti-obesity effects 247:301 the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii 247:348 This study investigated the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii in vitro and in vivo. 36828168 8 75 theme fibroblast 1062:1071 arg1 FGF-21 1091:1096 FGF-21 1091:1096 FGF-21 1091:1096 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 75 theme fibroblast 1062:1071 arg1 factor-21 1080:1088 fibroblast growth factor-21 1062:1088 fibroblast growth factor-21 (FGF-21) 1062:1097 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 8 75 theme fibroblast 1062:1071 arg1 levels 1038:1043 adipose specific hormone levels 1013:1043 adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) 1013:1098 Additionally, adipose specific hormone levels (adiponectin and fibroblast growth factor-21 (FGF-21)) were significantly decreased, and serum insulin levels were also decreased by STC, STCF1, and STCF3 treatment. 36828168 6 76 theme STCF1 849:853 arg1 administration 826:839 Oral administration 821:839 Oral administration of STC, STCF1, and STCF3 821:864 Oral administration of STC, STCF1, and STCF3 significantly reduced body weight and white adipose tissue (WAT) mass. 36828168 1 77 theme potential 251:259 arg1 effects 295:301 the potential lipid inhibitory and anti-obesity effects 247:301 the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii 247:348 This study investigated the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii in vitro and in vivo. 36828168 0 78 theme anti-hepatic 120:131 arg1 steatosis 133:141 anti-hepatic steatosis 120:141 anti-hepatic steatosis 120:141 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 0 79 theme gradient 53:60 arg1 precipitation 70:82 step gradient ethanol precipitation 48:82 step gradient ethanol precipitation 48:82 Fucoidan from Sargassum thunbergii obtained via step gradient ethanol precipitation indicate potential anti-obesity and anti-hepatic steatosis in vitro 3T3-L1 and HepG2 cells and in vivo high-fat diet-induced obesity mice. 36828168 9 80 theme free 1330:1333 arg1 oxidation 1346:1354 free fatty acid oxidation 1330:1354 free fatty acid oxidation in liver tissues 1330:1371 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 6 81 theme STC 844:846 arg1 administration 826:839 Oral administration 821:839 Oral administration of STC, STCF1, and STCF3 821:864 Oral administration of STC, STCF1, and STCF3 significantly reduced body weight and white adipose tissue (WAT) mass. 36828168 10 82 theme anti-obesity 1464:1475 arg1 effects 1477:1483 the potent anti-obesity effects 1453:1483 the potent anti-obesity effects 1453:1483 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 9 83 theme acid 1341:1344 arg1 oxidation 1346:1354 free fatty acid oxidation 1330:1354 free fatty acid oxidation in liver tissues 1330:1371 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 9 84 from oxidation 1346:1354 arg1 tissue 1318:1323 epididymal adipose tissue 1299:1323 epididymal adipose tissue 1299:1323 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 9 84 from oxidation 1346:1354 arg1 tissues 1365:1371 liver tissues 1359:1371 liver tissues 1359:1371 A mechanistic study revealed that the adipogenesis and lipolysis associated proteins in epididymal adipose tissue, and free fatty acid oxidation in liver tissues were effectively regulated by STC, STCF1, and STCF3. 36828168 10 85 theme obesity 1614:1620 arg1 mice 1628:1631 HFD-treated obesity model mice 1602:1631 HFD-treated obesity model mice 1602:1631 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 10 86 theme fatty 1570:1574 arg1 oxidation 1581:1589 the fatty acid oxidation 1566:1589 the fatty acid oxidation pathway 1566:1597 Overall, our findings show the potent anti-obesity effects of STC, STCF1, and STCF3, achieved by regulation of adipogenesis, lipolysis, and the fatty acid oxidation pathway in HFD-treated obesity model mice. 36828168 3 87 theme proximate 537:545 arg1 composition 547:557 their proximate composition 531:557 their proximate composition 531:557 We investigated their proximate composition, and anti-obesity effects in vitro and in vivo. 36828168 1 88 theme lipid 261:265 arg1 effects 295:301 the potential lipid inhibitory and anti-obesity effects 247:301 the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii 247:348 This study investigated the potential lipid inhibitory and anti-obesity effects of compounds derived from Sargassum thunbergii in vitro and in vivo. 36424929 6 0 theme T. 1203:1204 arg1 trifoliatus 1230:1240 T. fuciformis-Acanthopanax trifoliatus 1203:1240 T. fuciformis-Acanthopanax trifoliatus 1203:1240 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 8 1 theme composition 1565:1575 arg1 changes 1577:1583 the metabolite composition changes 1550:1583 the metabolite composition changes 1550:1583 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 2 theme fermentation 1777:1788 arg1 supernatant 1790:1800 fermentation supernatant 1777:1800 fermentation supernatant 1777:1800 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 2 3 theme % 626:626 arg1 v/v 629:631 2-8%, v/v 623:631 v/v 629:631 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 2 3 theme % 626:626 arg1 size 617:620 inoculum size 608:620 inoculum size (2-8%, v/v) 608:632 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 8 4 theme supernatant 1790:1800 arg1 metabolomics 1731:1742 untargeted metabolomics 1720:1742 untargeted metabolomics 1720:1742 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 4 theme supernatant 1790:1800 arg1 profile 1766:1772 the phytochemical profile 1748:1772 the phytochemical profile of fermentation supernatant 1748:1800 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 6 5 theme optimized 1165:1173 arg1 supernatant 1188:1198 the optimized fermentation supernatant 1161:1198 the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus 1161:1240 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 8 6 theme significant 1940:1950 arg1 increase 1952:1959 a significant increase 1938:1959 a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, 1938:2110 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 2 7 from effect 418:423 arg1 content 474:480 the total phenolic content 455:480 the total phenolic content 455:480 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 1 8 from utilization 328:338 arg1 supernatant 401:411 fermentation supernatant 388:411 fermentation supernatant 388:411 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 9 9 theme health 2316:2321 arg1 beverages 2351:2359 functional beverages 2340:2359 functional beverages 2340:2359 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 9 9 theme health 2316:2321 arg1 products 2323:2330 health products 2316:2330 health products such as functional beverages, cosmetics, and pharmaceutical raw materials 2316:2404 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 9 9 theme health 2316:2321 arg1 materials 2396:2404 pharmaceutical raw materials 2377:2404 pharmaceutical raw materials 2377:2404 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 9 9 theme health 2316:2321 arg1 cosmetics 2362:2370 cosmetics 2362:2370 cosmetics 2362:2370 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 1 10 theme bidirectional 205:217 arg1 system 232:237 a bidirectional fermentation system 203:237 a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant 203:411 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 4 11 theme polysaccharides 876:890 arg1 content 844:850 The content 840:850 The content of total flavonoids and polysaccharides 840:890 The content of total flavonoids and polysaccharides reached 78.65 ± 0.82 μg/mL and 9358.08 ± 122.96 μg/mL, respectively. 36424929 1 12 from transformation 309:322 arg1 supernatant 401:411 fermentation supernatant 388:411 fermentation supernatant 388:411 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 5 13 theme clearance 996:1004 arg1 rates 1006:1010 ⋅OH clearance rates 992:1010 ⋅OH clearance rates 992:1010 In addition, ABTS+, DPPH⋅, and ⋅OH clearance rates reached 95.09, 88.85, and 85.36% at 24 h under optimized conditions, respectively. 36424929 8 14 theme ultra-high 1628:1637 arg1 UPLC-MS/MS 1699:1708 UPLC-MS/MS 1699:1708 UPLC-MS/MS 1699:1708 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 14 theme ultra-high 1628:1637 arg1 spectrometry 1685:1696 ultra-high performance liquid chromatography-tandem mass spectrometry 1628:1696 ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation 1628:2142 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 6 15 theme polysaccharides 1142:1156 arg1 content 1099:1105 The content 1095:1105 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus 1095:1240 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 3 16 theme total 742:746 arg1 content 757:763 a maximum total phenolic content 732:763 a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture 732:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 0 17 theme surface 152:158 arg1 methodology 160:170 response surface methodology 143:170 response surface methodology 143:170 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 8 18 theme antioxidant 1964:1974 arg1 acid 2026:2029 ellagic acid 2018:2029 ellagic acid 2018:2029 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 18 theme antioxidant 1964:1974 arg1 compounds 1999:2007 flavonoid compounds 1989:2007 flavonoid compounds 1989:2007 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 19 theme liquid 1651:1656 arg1 UPLC-MS/MS 1699:1708 UPLC-MS/MS 1699:1708 UPLC-MS/MS 1699:1708 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 19 theme liquid 1651:1656 arg1 spectrometry 1685:1696 ultra-high performance liquid chromatography-tandem mass spectrometry 1628:1696 ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation 1628:2142 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 7 20 theme ⋅OH 1487:1489 arg1 rates 1501:1505 ⋅OH clearance rates 1487:1505 ⋅OH clearance rates 1487:1505 Simultaneously, 0.30 ± 0.00, 0.26 ± 0.01, and 1.19 ± 0.12 times increase of antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates were observed, respectively. 36424929 6 21 theme flavonoids 1127:1136 arg1 content 1099:1105 The content 1095:1105 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus 1095:1240 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 2 22 theme inoculum 608:615 arg1 v/v 629:631 2-8%, v/v 623:631 v/v 629:631 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 2 22 theme inoculum 608:615 arg1 size 617:620 inoculum size 608:620 inoculum size (2-8%, v/v) 608:632 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 7 23 dep times 1422:1426 arg1 increase 1428:1435 increase 1428:1435 0.30 ± 0.00, 0.26 ± 0.01, and 1.19 ± 0.12 times increase of antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates 1380:1505 Simultaneously, 0.30 ± 0.00, 0.26 ± 0.01, and 1.19 ± 0.12 times increase of antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates were observed, respectively. 36424929 8 24 theme mass 1680:1683 arg1 UPLC-MS/MS 1699:1708 UPLC-MS/MS 1699:1708 UPLC-MS/MS 1699:1708 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 24 theme mass 1680:1683 arg1 spectrometry 1685:1696 ultra-high performance liquid chromatography-tandem mass spectrometry 1628:1696 ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation 1628:2142 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 4 25 theme flavonoids 861:870 arg1 content 844:850 The content 840:850 The content of total flavonoids and polysaccharides 840:890 The content of total flavonoids and polysaccharides reached 78.65 ± 0.82 μg/mL and 9358.08 ± 122.96 μg/mL, respectively. 36424929 1 26 dep transformation 309:322 arg1 the 305:307 the 305:307 the 305:307 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 6 27 theme phenolics 1116:1124 arg1 content 1099:1105 The content 1095:1105 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus 1095:1240 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 3 28 theme 314.79 768:773 arg1 μg/mL 782:786 314.79 ± 6.89 μg/mL 768:786 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture 768:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 6 29 theme trifoliatus 1230:1240 arg1 supernatant 1188:1198 the optimized fermentation supernatant 1161:1198 the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus 1161:1240 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 3 30 theme optimized 639:647 arg1 parameters 662:671 The optimized fermentation parameters 635:671 The optimized fermentation parameters 635:671 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 3 30 theme optimized 639:647 arg1 28°C 679:682 28°C 679:682 28°C 679:682 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 3 31 theme fermentation 795:806 arg1 supernatant 808:818 the fermentation supernatant 791:818 the fermentation supernatant after 24 h culture 791:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 4 32 theme ± 931:931 arg1 μg/mL 940:944 9358.08 ± 122.96 μg/mL 923:944 9358.08 ± 122.96 μg/mL 923:944 The content of total flavonoids and polysaccharides reached 78.65 ± 0.82 μg/mL and 9358.08 ± 122.96 μg/mL, respectively. 36424929 0 33 from Acanthopanax 100:111 arg1 profile 9:15 Chemical profile 0:15 Chemical profile 0:15 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 0 33 from Acanthopanax 100:111 arg1 activity 33:40 antioxidant activity 21:40 antioxidant activity 21:40 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 0 33 from Acanthopanax 100:111 arg1 metabolites 59:69 bidirectional metabolites 45:69 bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus 45:123 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 1 34 theme fermentation 388:399 arg1 supernatant 401:411 fermentation supernatant 388:411 fermentation supernatant 388:411 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 9 35 theme pharmaceutical 2377:2390 arg1 materials 2396:2404 pharmaceutical raw materials 2377:2404 pharmaceutical raw materials 2377:2404 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 9 36 contain have 2285:2288 arg1 broth 2197:2201 the fermentation broth 2180:2201 the fermentation broth of T. fuciformis and A. trifoliatus 2180:2237 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 9 36 contain have 2285:2288 arg2 application 2300:2310 potential application 2290:2310 potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials 2290:2404 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 6 37 from content 1099:1105 arg1 supernatant 1188:1198 the optimized fermentation supernatant 1161:1198 the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus 1161:1240 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 6 38 from times 1298:1302 arg1 trifoliatus 1337:1347 A. trifoliatus 1334:1347 A. trifoliatus 1334:1347 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 3 39 theme h 829:829 arg1 culture 831:837 24 h culture 826:837 24 h culture 826:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 7 40 theme antioxidant 1440:1450 arg1 activity 1452:1459 antioxidant activity 1440:1459 antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates 1440:1505 Simultaneously, 0.30 ± 0.00, 0.26 ± 0.01, and 1.19 ± 0.12 times increase of antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates were observed, respectively. 36424929 8 41 dep differentiated 1802:1815 arg1 based 1831:1835 based 1831:1835 differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation 1802:2142 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 2 42 from methodology 522:532 arg1 terms 537:541 terms 537:541 terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v) 537:632 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 2 43 theme phenolic 465:472 arg1 content 474:480 the total phenolic content 455:480 the total phenolic content 455:480 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 0 44 dep Acanthopanax 100:111 arg1 trifoliatus 113:123 Acanthopanax trifoliatus 100:123 Acanthopanax trifoliatus 100:123 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 0 45 from activity 33:40 arg1 Tremella 76:83 Tremella 76:83 Tremella 76:83 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 0 45 from activity 33:40 arg1 Acanthopanax 100:111 Acanthopanax 100:111 Acanthopanax 100:111 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 9 46 theme fermentation 2184:2195 arg1 broth 2197:2201 the fermentation broth 2180:2201 the fermentation broth of T. fuciformis and A. trifoliatus 2180:2237 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 0 47 theme Chemical 0:7 arg1 profile 9:15 Chemical profile 0:15 Chemical profile 0:15 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 8 48 from h. 1922:1923 arg1 fermentation 1895:1906 fermentation 1895:1906 fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation 1895:2142 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 2 49 theme surface 514:520 arg1 methodology 522:532 response surface methodology 505:532 response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v) 505:632 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 7 50 dep 0.00 1387:1390 arg1 0.01 1400:1403 0.01 1400:1403 0.01 1400:1403 Simultaneously, 0.30 ± 0.00, 0.26 ± 0.01, and 1.19 ± 0.12 times increase of antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates were observed, respectively. 36424929 2 51 theme factors 552:558 arg1 terms 537:541 terms 537:541 terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v) 537:632 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 9 52 theme fuciformis 2209:2218 arg1 broth 2197:2201 the fermentation broth 2180:2201 the fermentation broth of T. fuciformis and A. trifoliatus 2180:2237 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 6 53 theme aqueous 1312:1318 arg1 extracts 1320:1327 aqueous extracts 1312:1327 aqueous extracts from A. trifoliatus 1312:1347 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 1 54 theme synthesized 347:357 arg1 metabolites 371:381 the synthesized antioxidant metabolites 343:381 the synthesized antioxidant metabolites from fermentation supernatant 343:411 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 8 55 theme phenolic 1976:1983 arg1 acid 2026:2029 ellagic acid 2018:2029 ellagic acid 2018:2029 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 55 theme phenolic 1976:1983 arg1 compounds 1999:2007 flavonoid compounds 1989:2007 flavonoid compounds 1989:2007 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 3 56 from content 757:763 arg1 supernatant 808:818 the fermentation supernatant 791:818 the fermentation supernatant after 24 h culture 791:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 0 57 theme bidirectional 45:57 arg1 metabolites 59:69 bidirectional metabolites 45:69 bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus 45:123 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 5 58 theme optimized 1059:1067 arg1 conditions 1069:1078 optimized conditions 1059:1078 optimized conditions 1059:1078 In addition, ABTS+, DPPH⋅, and ⋅OH clearance rates reached 95.09, 88.85, and 85.36% at 24 h under optimized conditions, respectively. 36424929 8 59 theme luteolin 2042:2049 arg1 acid 2026:2029 ellagic acid 2018:2029 ellagic acid 2018:2029 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 59 theme luteolin 2042:2049 arg1 -gallocatechin 2096:2109 luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin 2042:2109 luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin 2042:2109 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 2 60 theme conditions 441:450 arg1 effect 418:423 The effect 414:423 The effect of fermentation conditions on the total phenolic content 414:480 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 3 61 theme inoculum 698:705 arg1 size 707:710 an inoculum size 695:710 an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture 695:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 6 62 theme fuciformis-Acanthopanax 1206:1228 arg1 trifoliatus 1230:1240 T. fuciformis-Acanthopanax trifoliatus 1203:1240 T. fuciformis-Acanthopanax trifoliatus 1203:1240 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 8 63 theme metabolite 1554:1563 arg1 changes 1577:1583 the metabolite composition changes 1550:1583 the metabolite composition changes 1550:1583 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 64 dep h. 1922:1923 arg1 to 1916:1917 to 1916:1917 to 1916:1917 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 64 dep h. 1922:1923 arg1 observed 2116:2123 observed 2116:2123 was observed after fermentation 2112:2142 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 3 65 theme % 716:716 arg1 pH 685:686 pH 8 685:688 pH 8 685:688 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 3 65 theme % 716:716 arg1 size 707:710 an inoculum size 695:710 an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture 695:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 3 65 theme % 716:716 arg1 28°C 679:682 28°C 679:682 28°C 679:682 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 3 65 theme % 716:716 arg1 parameters 662:671 The optimized fermentation parameters 635:671 The optimized fermentation parameters 635:671 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 6 66 theme fermentation 1175:1186 arg1 supernatant 1188:1198 the optimized fermentation supernatant 1161:1198 the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus 1161:1240 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 9 67 theme potential 2290:2298 arg1 application 2300:2310 potential application 2290:2310 potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials 2290:2404 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 8 68 theme flavonoid 1989:1997 arg1 acid 2026:2029 ellagic acid 2018:2029 ellagic acid 2018:2029 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 68 theme flavonoid 1989:1997 arg1 compounds 1999:2007 flavonoid compounds 1989:2007 flavonoid compounds 1989:2007 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 1 69 theme metabolites 371:381 arg1 utilization 328:338 utilization 328:338 utilization 328:338 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 1 69 theme metabolites 371:381 arg1 transformation 309:322 transformation 309:322 transformation 309:322 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 8 70 theme unsupervised 1840:1851 arg1 analysis 1873:1880 unsupervised principal component analysis 1840:1880 unsupervised principal component analysis (PCA) 1840:1886 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 70 theme unsupervised 1840:1851 arg1 PCA 1883:1885 PCA 1883:1885 PCA 1883:1885 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 71 from increase 1952:1959 arg1 acid 2026:2029 ellagic acid 2018:2029 ellagic acid 2018:2029 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 71 from increase 1952:1959 arg1 compounds 1999:2007 flavonoid compounds 1989:2007 flavonoid compounds 1989:2007 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 3 72 from supernatant 808:818 arg1 content 757:763 a maximum total phenolic content 732:763 a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture 732:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 1 73 from supernatant 401:411 arg1 metabolites 371:381 the synthesized antioxidant metabolites 343:381 the synthesized antioxidant metabolites from fermentation supernatant 343:411 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 1 73 from supernatant 401:411 arg1 utilization 328:338 utilization 328:338 utilization 328:338 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 1 73 from supernatant 401:411 arg1 transformation 309:322 transformation 309:322 transformation 309:322 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 0 74 theme response 143:150 arg1 methodology 160:170 response surface methodology 143:170 response surface methodology 143:170 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 1 75 theme fermentation 219:230 arg1 system 232:237 a bidirectional fermentation system 203:237 a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant 203:411 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 7 76 theme clearance 1491:1499 arg1 rates 1501:1505 ⋅OH clearance rates 1487:1505 ⋅OH clearance rates 1487:1505 Simultaneously, 0.30 ± 0.00, 0.26 ± 0.01, and 1.19 ± 0.12 times increase of antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates were observed, respectively. 36424929 9 77 contain had 2239:2241 arg2 activity 2267:2274 significant antioxidant activity 2243:2274 significant antioxidant activity 2243:2274 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 9 77 contain had 2239:2241 arg1 broth 2197:2201 the fermentation broth 2180:2201 the fermentation broth of T. fuciformis and A. trifoliatus 2180:2237 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 1 78 dep Acanthopanax 269:280 arg1 trifoliatus 282:292 Acanthopanax trifoliatus 269:292 Acanthopanax trifoliatus 269:292 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 0 79 from Tremella 76:83 arg1 profile 9:15 Chemical profile 0:15 Chemical profile 0:15 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 0 79 from Tremella 76:83 arg1 activity 33:40 antioxidant activity 21:40 antioxidant activity 21:40 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 0 79 from Tremella 76:83 arg1 metabolites 59:69 bidirectional metabolites 45:69 bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus 45:123 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 3 80 theme phenolic 748:755 arg1 content 757:763 a maximum total phenolic content 732:763 a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture 732:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 6 81 from trifoliatus 1337:1347 arg1 ± 1273:1273 0.09 ± 0.02 1268:1278 0.09 ± 0.02 1268:1278 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 6 81 from trifoliatus 1337:1347 arg1 extracts 1320:1327 aqueous extracts 1312:1327 aqueous extracts from A. trifoliatus 1312:1347 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 6 81 from trifoliatus 1337:1347 arg1 ± 1260:1260 0.88 ± 0.04 1255:1265 0.88 ± 0.04 1255:1265 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 6 81 from trifoliatus 1337:1347 arg1 times 1298:1302 33.84 ± 1.85 times 1285:1302 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus 1285:1347 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 8 82 theme performance 1639:1649 arg1 UPLC-MS/MS 1699:1708 UPLC-MS/MS 1699:1708 UPLC-MS/MS 1699:1708 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 82 theme performance 1639:1649 arg1 spectrometry 1685:1696 ultra-high performance liquid chromatography-tandem mass spectrometry 1628:1696 ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation 1628:2142 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 83 theme component 1863:1871 arg1 analysis 1873:1880 unsupervised principal component analysis 1840:1880 unsupervised principal component analysis (PCA) 1840:1886 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 83 theme component 1863:1871 arg1 PCA 1883:1885 PCA 1883:1885 PCA 1883:1885 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 3 84 theme maximum 734:740 arg1 content 757:763 a maximum total phenolic content 732:763 a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture 732:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 8 85 theme chromatography-tandem 1658:1678 arg1 UPLC-MS/MS 1699:1708 UPLC-MS/MS 1699:1708 UPLC-MS/MS 1699:1708 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 85 theme chromatography-tandem 1658:1678 arg1 spectrometry 1685:1696 ultra-high performance liquid chromatography-tandem mass spectrometry 1628:1696 ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation 1628:2142 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 3 86 theme 24 826:827 arg1 h 829:829 h 829:829 h 829:829 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 4 87 theme total 855:859 arg1 flavonoids 861:870 total flavonoids 855:870 total flavonoids 855:870 The content of total flavonoids and polysaccharides reached 78.65 ± 0.82 μg/mL and 9358.08 ± 122.96 μg/mL, respectively. 36424929 6 88 theme total 1110:1114 arg1 phenolics 1116:1124 total phenolics 1110:1124 total phenolics 1110:1124 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 3 89 theme ± 775:775 arg1 μg/mL 782:786 314.79 ± 6.89 μg/mL 768:786 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture 768:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 5 90 theme ⋅OH 992:994 arg1 rates 1006:1010 ⋅OH clearance rates 992:1010 ⋅OH clearance rates 992:1010 In addition, ABTS+, DPPH⋅, and ⋅OH clearance rates reached 95.09, 88.85, and 85.36% at 24 h under optimized conditions, respectively. 36424929 7 91 theme activity 1452:1459 arg1 increase 1428:1435 increase 1428:1435 0.30 ± 0.00, 0.26 ± 0.01, and 1.19 ± 0.12 times increase of antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates 1380:1505 Simultaneously, 0.30 ± 0.00, 0.26 ± 0.01, and 1.19 ± 0.12 times increase of antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates were observed, respectively. 36424929 6 92 theme ± 1291:1291 arg1 times 1298:1302 33.84 ± 1.85 times 1285:1302 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus 1285:1347 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 9 93 theme raw 2392:2394 arg1 materials 2396:2404 pharmaceutical raw materials 2377:2404 pharmaceutical raw materials 2377:2404 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 8 94 theme principal 1853:1861 arg1 analysis 1873:1880 unsupervised principal component analysis 1840:1880 unsupervised principal component analysis (PCA) 1840:1886 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 94 theme principal 1853:1861 arg1 PCA 1883:1885 PCA 1883:1885 PCA 1883:1885 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 0 95 from profile 9:15 arg1 Tremella 76:83 Tremella 76:83 Tremella 76:83 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 0 95 from profile 9:15 arg1 Acanthopanax 100:111 Acanthopanax 100:111 Acanthopanax 100:111 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 4 96 theme ± 906:906 arg1 μg/mL 913:917 78.65 ± 0.82 μg/mL 900:917 78.65 ± 0.82 μg/mL 900:917 The content of total flavonoids and polysaccharides reached 78.65 ± 0.82 μg/mL and 9358.08 ± 122.96 μg/mL, respectively. 36424929 3 97 theme μg/mL 782:786 arg1 content 757:763 a maximum total phenolic content 732:763 a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture 732:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 6 98 from ± 1273:1273 arg1 trifoliatus 1337:1347 A. trifoliatus 1334:1347 A. trifoliatus 1334:1347 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 8 99 theme untargeted 1720:1729 arg1 metabolomics 1731:1742 untargeted metabolomics 1720:1742 untargeted metabolomics 1720:1742 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 2 100 theme total 459:463 arg1 content 474:480 the total phenolic content 455:480 the total phenolic content 455:480 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 8 101 theme ellagic 2018:2024 arg1 vanillin 2032:2039 vanillin 2032:2039 vanillin 2032:2039 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 101 theme ellagic 2018:2024 arg1 -gallocatechin 2096:2109 luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin 2042:2109 luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin 2042:2109 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 101 theme ellagic 2018:2024 arg1 acid 2026:2029 ellagic acid 2018:2029 ellagic acid 2018:2029 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 8 102 dep caused 1585:1590 arg1 analyzed 1613:1620 analyzed 1613:1620 were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation 1608:2142 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 0 103 theme antioxidant 21:31 arg1 activity 33:40 antioxidant activity 21:40 antioxidant activity 21:40 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 6 104 from ± 1260:1260 arg1 trifoliatus 1337:1347 A. trifoliatus 1334:1347 A. trifoliatus 1334:1347 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 8 105 theme phytochemical 1752:1764 arg1 profile 1766:1772 the phytochemical profile 1748:1772 the phytochemical profile of fermentation supernatant 1748:1800 Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. 36424929 0 106 dep Tremella 76:83 arg1 fuciformis 85:94 Tremella fuciformis 76:94 Tremella fuciformis 76:94 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 2 107 theme response 505:512 arg1 methodology 522:532 response surface methodology 505:532 response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v) 505:632 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36424929 3 108 from μg/mL 782:786 arg1 supernatant 808:818 the fermentation supernatant 791:818 the fermentation supernatant after 24 h culture 791:837 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 9 109 theme antioxidant 2255:2265 arg1 activity 2267:2274 significant antioxidant activity 2243:2274 significant antioxidant activity 2243:2274 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 6 110 theme extracts 1320:1327 arg1 ± 1273:1273 0.09 ± 0.02 1268:1278 0.09 ± 0.02 1268:1278 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 6 110 theme extracts 1320:1327 arg1 ± 1260:1260 0.88 ± 0.04 1255:1265 0.88 ± 0.04 1255:1265 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 6 110 theme extracts 1320:1327 arg1 times 1298:1302 33.84 ± 1.85 times 1285:1302 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus 1285:1347 The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. 36424929 3 111 theme fermentation 649:660 arg1 parameters 662:671 The optimized fermentation parameters 635:671 The optimized fermentation parameters 635:671 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 3 111 theme fermentation 649:660 arg1 28°C 679:682 28°C 679:682 28°C 679:682 The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 μg/mL in the fermentation supernatant after 24 h culture. 36424929 0 112 theme metabolites 59:69 arg1 profile 9:15 Chemical profile 0:15 Chemical profile 0:15 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 0 112 theme metabolites 59:69 arg1 activity 33:40 antioxidant activity 21:40 antioxidant activity 21:40 Chemical profile and antioxidant activity of bidirectional metabolites from Tremella fuciformis and Acanthopanax trifoliatus as assessed using response surface methodology. 36424929 1 113 theme antioxidant 359:369 arg1 metabolites 371:381 the synthesized antioxidant metabolites 343:381 the synthesized antioxidant metabolites from fermentation supernatant 343:411 This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. 36424929 9 114 theme trifoliatus 2227:2237 arg1 broth 2197:2201 the fermentation broth 2180:2201 the fermentation broth of T. fuciformis and A. trifoliatus 2180:2237 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 9 115 theme functional 2340:2349 arg1 beverages 2351:2359 functional beverages 2340:2359 functional beverages 2340:2359 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 9 116 theme significant 2243:2253 arg1 activity 2267:2274 significant antioxidant activity 2243:2274 significant antioxidant activity 2243:2274 Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials. 36424929 2 117 theme fermentation 428:439 arg1 conditions 441:450 fermentation conditions 428:450 fermentation conditions 428:450 The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). 36409123 11 0 theme major 2098:2102 arg1 proteins 2070:2077 its surface proteins 2058:2077 its surface proteins 2058:2077 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 11 0 theme major 2098:2102 arg1 O-glycans 2104:2112 the more abundant major O-glycans 2080:2112 the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose 2080:2186 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 2 1 theme CAP6 364:367 arg1 gene 369:372 the C. neoformans CAP6 gene 346:372 the C. neoformans CAP6 gene 346:372 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 14 2 theme stress 2504:2509 arg1 sensors 2511:2517 two novel C. neoformans stress sensors 2480:2517 two novel C. neoformans stress sensors that require Ktr3- and Cap6-mediated posttranslational modification for full function 2480:2603 We also identified two novel C. neoformans stress sensors that require Ktr3- and Cap6-mediated posttranslational modification for full function. 36409123 9 3 theme reduced 1648:1654 arg1 induction 1656:1664 reduced induction 1648:1664 reduced induction of the host immune response 1648:1692 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 16 4 theme infection 2816:2824 arg1 model 2826:2830 a mouse infection model 2808:2830 a mouse infection model 2808:2830 Furthermore, the ktr3Δ cap6Δ strain is completely avirulent in a mouse infection model. 36409123 10 5 theme host 1951:1954 arg1 cells 1956:1960 host cells 1951:1960 host cells 1951:1960 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 15 6 theme signaling 2692:2700 arg1 pathways 2702:2709 stress signaling pathways 2685:2709 stress signaling pathways 2685:2709 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 14 7 theme C. 2490:2491 arg1 sensors 2511:2517 two novel C. neoformans stress sensors 2480:2517 two novel C. neoformans stress sensors that require Ktr3- and Cap6-mediated posttranslational modification for full function 2480:2603 We also identified two novel C. neoformans stress sensors that require Ktr3- and Cap6-mediated posttranslational modification for full function. 36409123 6 8 theme genes 1177:1181 arg1 expression 1163:1172 decreased expression 1153:1172 decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway 1153:1246 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 16 9 theme cap6Δ 2768:2772 arg1 strain 2774:2779 the ktr3Δ cap6Δ strain 2758:2779 the ktr3Δ cap6Δ strain 2758:2779 Furthermore, the ktr3Δ cap6Δ strain is completely avirulent in a mouse infection model. 36409123 16 9 theme cap6Δ 2768:2772 arg1 avirulent 2795:2803 avirulent 2795:2803 avirulent 2795:2803 Furthermore, the ktr3Δ cap6Δ strain is completely avirulent in a mouse infection model. 36409123 1 10 link O-linked 252:259 arg1 glycans 261:267 O-linked glycans 252:267 O-linked glycans 252:267 The human-pathogenic yeast Cryptococcus neoformans assembles two types of O-linked glycans on its proteins. 36409123 4 11 theme proteins 860:867 arg1 accumulation 844:855 the accumulation 840:855 the accumulation of proteins with O-glycans carrying only a single mannose 840:913 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 18 12 theme fungus-specific 2983:2997 arg1 mannosyltransferases 2999:3018 these fungus-specific mannosyltransferases 2977:3018 these fungus-specific mannosyltransferases 2977:3018 As there are no human homologs for Cap6 or Ktr3, these fungus-specific mannosyltransferases are novel targets for antifungal therapy. 36409123 1 13 theme yeast 199:203 arg1 neoformans 218:227 The human-pathogenic yeast Cryptococcus neoformans 178:227 The human-pathogenic yeast Cryptococcus neoformans 178:227 The human-pathogenic yeast Cryptococcus neoformans assembles two types of O-linked glycans on its proteins. 36409123 10 14 from resistance 1919:1928 arg1 neoformans 1968:1977 C. neoformans 1965:1977 C. neoformans 1965:1977 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 9 15 theme response 1685:1692 arg1 induction 1656:1664 reduced induction 1648:1664 reduced induction of the host immune response 1648:1692 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 9 15 theme response 1685:1692 arg1 trafficking 1708:1718 defective trafficking 1698:1718 defective trafficking of ergosterol, an immunoreactive fungal molecule 1698:1767 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 16 16 theme mouse 2810:2814 arg1 model 2826:2830 a mouse infection model 2808:2830 a mouse infection model 2808:2830 Furthermore, the ktr3Δ cap6Δ strain is completely avirulent in a mouse infection model. 36409123 11 17 theme xylose 2134:2139 arg1 residues 2141:2148 xylose residues 2134:2148 xylose residues 2134:2148 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 5 18 theme wml2Δ 1061:1065 arg1 strains 1067:1073 both ktr3Δ cap6Δ and wml1Δ wml2Δ strains 1034:1073 strains 1067:1073 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 3 19 theme sensor 534:539 arg1 Wml2 576:579 Wml2 576:579 Wml2 576:579 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 3 19 theme sensor 534:539 arg1 Wml1 551:554 Wml1 551:554 Wml1 (WSC/Mid2-like) 551:570 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 3 19 theme sensor 534:539 arg1 proteins 541:548 Two cell surface sensor proteins 517:548 Two cell surface sensor proteins 517:548 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 12 20 from role 2214:2217 arg1 synthesis 2263:2271 the synthesis 2259:2271 the synthesis of minor O-glycans 2259:2290 Here, we demonstrate the role of the Cap6 α1,3-mannosyltransferase in the synthesis of minor O-glycans. 36409123 11 21 dep IMPORTANCE 1980:1989 arg1 neoformans 2004:2013 Cryptococcus neoformans 1991:2013 IMPORTANCE Cryptococcus neoformans 1980:2013 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 10 22 from interaction 1934:1944 arg1 neoformans 1968:1977 C. neoformans 1965:1977 C. neoformans 1965:1977 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 9 23 theme defective 1698:1706 arg1 trafficking 1708:1718 defective trafficking 1698:1718 defective trafficking of ergosterol, an immunoreactive fungal molecule 1698:1767 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 8 24 theme ktr3Δ 1435:1439 arg1 strain 1447:1452 the ktr3Δ cap6Δ strain 1431:1452 the ktr3Δ cap6Δ strain 1431:1452 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 16 25 theme ktr3Δ 2762:2766 arg1 strain 2774:2779 the ktr3Δ cap6Δ strain 2758:2779 the ktr3Δ cap6Δ strain 2758:2779 Furthermore, the ktr3Δ cap6Δ strain is completely avirulent in a mouse infection model. 36409123 16 25 theme ktr3Δ 2762:2766 arg1 avirulent 2795:2803 avirulent 2795:2803 avirulent 2795:2803 Furthermore, the ktr3Δ cap6Δ strain is completely avirulent in a mouse infection model. 36409123 11 26 contain contain 2126:2132 arg2 O-glycans 2160:2168 minor O-glycans 2154:2168 minor O-glycans containing xylose 2154:2186 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 11 26 contain contain 2126:2132 arg2 residues 2141:2148 xylose residues 2134:2148 xylose residues 2134:2148 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 11 26 contain contain 2126:2132 arg1 proteins 2070:2077 its surface proteins 2058:2077 its surface proteins 2058:2077 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 11 26 contain contain 2126:2132 arg1 O-glycans 2104:2112 the more abundant major O-glycans 2080:2112 the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose 2080:2186 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 0 27 theme Host 126:129 arg1 Cells 131:135 Host Cells 126:135 Host Cells 126:135 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 3 28 theme independent 599:609 arg1 substrates 611:620 independent substrates 599:620 independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively 599:696 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 13 29 theme capsule 2331:2337 arg1 biosynthesis 2339:2350 capsule biosynthesis 2331:2350 capsule biosynthesis 2331:2350 Previously proposed to be involved in capsule biosynthesis, Cap6 works with the related Ktr3 α1,2-mannosyltransferase to synthesize O-glycans on their target proteins. 36409123 10 30 theme critical 1833:1840 arg1 roles 1842:1846 critical roles 1833:1846 critical roles 1833:1846 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 4 31 theme single 900:905 arg1 mannose 907:913 only a single mannose 893:913 only a single mannose 893:913 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 7 32 theme mouse 1361:1365 arg1 model 1367:1371 a mouse model 1359:1371 a mouse model of cryptococcosis 1359:1389 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 4 33 theme CAP6 731:734 arg1 deletion 710:717 The double deletion 699:717 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) 699:748 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 5 34 theme ktr3Δ 1039:1043 arg1 cap6Δ 1045:1049 both ktr3Δ cap6Δ and wml1Δ wml2Δ strains 1034:1073 cap6Δ 1045:1049 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 0 35 from Signaling 95:103 arg1 neoformans 153:162 Cryptococcus neoformans 140:162 Cryptococcus neoformans 140:162 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 6 36 theme wall 1219:1222 arg1 CWI 1235:1237 CWI 1235:1237 CWI 1235:1237 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 6 36 theme wall 1219:1222 arg1 integrity 1224:1232 Mpk1-dependent cell wall integrity 1199:1232 the Mpk1-dependent cell wall integrity (CWI) pathway 1195:1246 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 3 37 theme minor 639:643 arg1 O-mannosylation 668:682 Cap6-mediated minor or Ktr3-mediated major O-mannosylation 625:682 Cap6-mediated minor or Ktr3-mediated major O-mannosylation 625:682 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 16 38 from avirulent 2795:2803 arg1 model 2826:2830 a mouse infection model 2808:2830 a mouse infection model 2808:2830 Furthermore, the ktr3Δ cap6Δ strain is completely avirulent in a mouse infection model. 36409123 9 39 theme immunoreactive 1738:1751 arg1 molecule 1760:1767 an immunoreactive fungal molecule 1735:1767 an immunoreactive fungal molecule 1735:1767 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 9 39 theme immunoreactive 1738:1751 arg1 ergosterol 1723:1732 ergosterol 1723:1732 ergosterol 1723:1732 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 6 40 theme Mpk1-dependent 1199:1212 arg1 CWI 1235:1237 CWI 1235:1237 CWI 1235:1237 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 6 40 theme Mpk1-dependent 1199:1212 arg1 integrity 1224:1232 Mpk1-dependent cell wall integrity 1199:1232 the Mpk1-dependent cell wall integrity (CWI) pathway 1195:1246 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 0 41 with Interaction 109:119 arg1 Cells 131:135 Host Cells 126:135 Host Cells 126:135 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 4 42 with proteins 860:867 arg1 O-glycans 874:882 O-glycans 874:882 O-glycans carrying only a single mannose 874:913 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 8 43 theme epithelial 1488:1497 arg1 cells 1499:1503 lung epithelial cells 1483:1503 lung epithelial cells 1483:1503 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 4 44 theme KTR3 722:725 arg1 deletion 710:717 The double deletion 699:717 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) 699:748 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 0 45 from Extension 0:8 arg1 Apparatus 49:57 the Golgi Apparatus 39:57 the Golgi Apparatus 39:57 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 4 46 theme mannose 773:779 arg1 addition 781:788 the mannose addition 769:788 the mannose addition 769:788 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 0 47 theme Wall 80:83 arg1 Integrity 85:93 Cell Wall Integrity 75:93 Cell Wall Integrity Signaling 75:103 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 18 48 theme human 2944:2948 arg1 homologs 2950:2957 no human homologs 2941:2957 no human homologs for Cap6 or Ktr3 2941:2974 As there are no human homologs for Cap6 or Ktr3, these fungus-specific mannosyltransferases are novel targets for antifungal therapy. 36409123 5 49 theme mitogen-activated 969:985 arg1 MAPK 1003:1006 MAPK 1003:1006 MAPK 1003:1006 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 5 49 theme mitogen-activated 969:985 arg1 kinase 995:1000 Mpk1 mitogen-activated protein kinase 964:1000 the Mpk1 mitogen-activated protein kinase (MAPK) 960:1007 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 2 50 from xylose 486:491 arg1 apparatus 506:514 the Golgi apparatus 496:514 the Golgi apparatus 496:514 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 5 51 theme kinase 995:1000 arg1 phosphorylation 941:955 Tunicamycin (TM)-induced phosphorylation 916:955 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) 916:1007 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 10 52 with signaling 1898:1906 arg1 cells 1956:1960 host cells 1951:1960 host cells 1951:1960 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 12 53 theme minor 2276:2280 arg1 O-glycans 2282:2290 minor O-glycans 2276:2290 minor O-glycans 2276:2290 Here, we demonstrate the role of the Cap6 α1,3-mannosyltransferase in the synthesis of minor O-glycans. 36409123 11 54 link O-linked 2038:2045 arg1 glycans 2047:2053 O-linked glycans 2038:2053 O-linked glycans 2038:2053 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 7 55 theme ktr3Δ 1323:1327 arg1 avirulent 1346:1354 avirulent 1346:1354 avirulent 1346:1354 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 7 55 theme ktr3Δ 1323:1327 arg1 strain 1335:1340 the ktr3Δ cap6Δ strain 1319:1340 the ktr3Δ cap6Δ strain 1319:1340 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 2 56 theme minor 459:463 arg1 O-glycans 465:473 minor O-glycans 459:473 minor O-glycans containing xylose in the Golgi apparatus 459:514 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 13 57 from O-glycans 2425:2433 arg1 proteins 2451:2458 their target proteins 2438:2458 their target proteins 2438:2458 Previously proposed to be involved in capsule biosynthesis, Cap6 works with the related Ktr3 α1,2-mannosyltransferase to synthesize O-glycans on their target proteins. 36409123 0 58 theme O-Linked 13:20 arg1 Mannosylation 22:34 O-Linked Mannosylation 13:34 O-Linked Mannosylation 13:34 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 2 59 theme Golgi 500:504 arg1 apparatus 506:514 the Golgi apparatus 496:514 the Golgi apparatus 496:514 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 3 60 theme O-mannosylation 668:682 arg1 substrates 611:620 independent substrates 599:620 independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively 599:696 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 2 61 theme second 432:437 arg1 addition 447:454 the second mannose addition 428:454 the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus 428:514 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 8 62 dep showed 1454:1459 arg1 decreased 1506:1514 decreased 1506:1514 decreased proliferation within macrophages 1506:1547 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 8 62 dep showed 1454:1459 arg1 reduced 1554:1560 reduced 1554:1560 reduced transcytosis of the blood-brain barrier (BBB) 1554:1606 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 8 62 dep showed 1454:1459 arg1 decreased 1461:1469 decreased 1461:1469 decreased adhesion to lung epithelial cells 1461:1503 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 17 63 from roles 2878:2882 arg1 pathogenesis 2914:2925 fungal pathogenesis 2907:2925 fungal pathogenesis 2907:2925 Together, these results demonstrate critical roles for O-glycosylation in fungal pathogenesis. 36409123 7 64 theme stress 1300:1305 arg1 conditions 1307:1316 several stress conditions 1292:1316 several stress conditions 1292:1316 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 3 65 theme Ktr3-mediated 648:660 arg1 O-mannosylation 668:682 Cap6-mediated minor or Ktr3-mediated major O-mannosylation 625:682 Cap6-mediated minor or Ktr3-mediated major O-mannosylation 625:682 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 10 66 theme pathobiological 1859:1873 arg1 interaction 1934:1944 interaction 1934:1944 interaction with host cells in C. neoformans 1934:1977 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 10 66 theme pathobiological 1859:1873 arg1 signaling 1898:1906 CWI signaling 1894:1906 CWI signaling 1894:1906 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 10 66 theme pathobiological 1859:1873 arg1 processes 1875:1883 various pathobiological processes 1851:1883 various pathobiological processes 1851:1883 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 10 66 theme pathobiological 1859:1873 arg1 resistance 1919:1928 stress resistance 1912:1928 stress resistance 1912:1928 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 0 67 theme Golgi 43:47 arg1 Apparatus 49:57 the Golgi Apparatus 39:57 the Golgi Apparatus 39:57 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 14 68 theme posttranslational 2556:2572 arg1 modification 2574:2585 Cap6-mediated posttranslational modification 2542:2585 Cap6-mediated posttranslational modification 2542:2585 We also identified two novel C. neoformans stress sensors that require Ktr3- and Cap6-mediated posttranslational modification for full function. 36409123 8 69 theme barrier 1594:1600 arg1 transcytosis 1562:1573 transcytosis 1562:1573 transcytosis of the blood-brain barrier (BBB) 1562:1606 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 4 70 theme second 797:802 arg1 position 804:811 the second position 793:811 the second position of O-glycans 793:824 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 15 71 theme O-glycan 2642:2649 arg1 strain 2658:2663 the ktr3Δ cap6Δ double O-glycan mutant strain 2619:2663 the ktr3Δ cap6Δ double O-glycan mutant strain 2619:2663 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 7 72 theme defective 1269:1277 arg1 growth 1279:1284 its defective growth 1265:1284 its defective growth under several stress conditions 1265:1316 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 4 73 contain carrying 884:891 arg1 O-glycans 874:882 O-glycans 874:882 O-glycans carrying only a single mannose 874:913 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 4 73 contain carrying 884:891 arg2 mannose 907:913 only a single mannose 893:913 only a single mannose 893:913 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 15 74 theme cap6Δ 2629:2633 arg1 strain 2658:2663 the ktr3Δ cap6Δ double O-glycan mutant strain 2619:2663 the ktr3Δ cap6Δ double O-glycan mutant strain 2619:2663 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 1 75 theme O-linked 252:259 arg1 glycans 261:267 O-linked glycans 252:267 O-linked glycans 252:267 The human-pathogenic yeast Cryptococcus neoformans assembles two types of O-linked glycans on its proteins. 36409123 9 76 theme cap6Δ 1628:1632 arg1 strain 1634:1639 the ktr3Δ cap6Δ strain 1618:1639 the ktr3Δ cap6Δ strain 1618:1639 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 0 77 from Interaction 109:119 arg1 neoformans 153:162 Cryptococcus neoformans 140:162 Cryptococcus neoformans 140:162 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 10 78 theme stress 1912:1917 arg1 resistance 1919:1928 stress resistance 1912:1928 stress resistance 1912:1928 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 15 79 theme ergosterol 2721:2730 arg1 trafficking 2732:2742 ergosterol trafficking 2721:2742 ergosterol trafficking 2721:2742 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 3 80 theme surface 526:532 arg1 Wml2 576:579 Wml2 576:579 Wml2 576:579 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 3 80 theme surface 526:532 arg1 Wml1 551:554 Wml1 551:554 Wml1 (WSC/Mid2-like) 551:570 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 3 80 theme surface 526:532 arg1 proteins 541:548 Two cell surface sensor proteins 517:548 Two cell surface sensor proteins 517:548 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 9 81 theme host 1673:1676 arg1 response 1685:1692 the host immune response 1669:1692 the host immune response 1669:1692 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 7 82 with Consistent 1249:1258 arg1 growth 1279:1284 its defective growth 1265:1284 its defective growth under several stress conditions 1265:1316 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 18 83 theme antifungal 3042:3051 arg1 therapy 3053:3059 antifungal therapy 3042:3059 antifungal therapy 3042:3059 As there are no human homologs for Cap6 or Ktr3, these fungus-specific mannosyltransferases are novel targets for antifungal therapy. 36409123 17 84 theme fungal 2907:2912 arg1 pathogenesis 2914:2925 fungal pathogenesis 2907:2925 fungal pathogenesis 2907:2925 Together, these results demonstrate critical roles for O-glycosylation in fungal pathogenesis. 36409123 2 85 contain containing 475:484 arg1 O-glycans 465:473 minor O-glycans 459:473 minor O-glycans containing xylose in the Golgi apparatus 459:514 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 2 85 contain containing 475:484 arg2 xylose 486:491 xylose 486:491 xylose in the Golgi apparatus 486:514 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 14 86 theme novel 2484:2488 arg1 sensors 2511:2517 two novel C. neoformans stress sensors 2480:2517 two novel C. neoformans stress sensors that require Ktr3- and Cap6-mediated posttranslational modification for full function 2480:2603 We also identified two novel C. neoformans stress sensors that require Ktr3- and Cap6-mediated posttranslational modification for full function. 36409123 11 87 theme minor 2154:2158 arg1 O-glycans 2160:2168 minor O-glycans 2154:2168 minor O-glycans containing xylose 2154:2186 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 0 88 with Signaling 95:103 arg1 Cells 131:135 Host Cells 126:135 Host Cells 126:135 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 10 89 theme O-glycan 1785:1792 arg1 extension 1794:1802 O-glycan extension 1785:1802 O-glycan extension in the Golgi apparatus 1785:1825 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 15 90 theme stress 2685:2690 arg1 pathways 2702:2709 stress signaling pathways 2685:2709 stress signaling pathways 2685:2709 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 1 91 theme human-pathogenic 182:197 arg1 neoformans 218:227 The human-pathogenic yeast Cryptococcus neoformans 178:227 The human-pathogenic yeast Cryptococcus neoformans 178:227 The human-pathogenic yeast Cryptococcus neoformans assembles two types of O-linked glycans on its proteins. 36409123 10 92 from signaling 1898:1906 arg1 neoformans 1968:1977 C. neoformans 1965:1977 C. neoformans 1965:1977 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 9 93 theme immune 1678:1683 arg1 response 1685:1692 the host immune response 1669:1692 the host immune response 1669:1692 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 6 94 theme decreased 1153:1161 arg1 expression 1163:1172 decreased expression 1153:1172 decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway 1153:1246 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 11 95 theme O-linked 2038:2045 arg1 glycans 2047:2053 O-linked glycans 2038:2053 O-linked glycans 2038:2053 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 1 96 theme Cryptococcus 205:216 arg1 neoformans 218:227 The human-pathogenic yeast Cryptococcus neoformans 178:227 The human-pathogenic yeast Cryptococcus neoformans 178:227 The human-pathogenic yeast Cryptococcus neoformans assembles two types of O-linked glycans on its proteins. 36409123 8 97 theme cap6Δ 1441:1445 arg1 strain 1447:1452 the ktr3Δ cap6Δ strain 1431:1452 the ktr3Δ cap6Δ strain 1431:1452 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 2 98 theme C. 350:351 arg1 gene 369:372 the C. neoformans CAP6 gene 346:372 the C. neoformans CAP6 gene 346:372 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 10 99 theme Golgi 1811:1815 arg1 apparatus 1817:1825 the Golgi apparatus 1807:1825 the Golgi apparatus 1807:1825 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 16 100 from model 2826:2830 arg1 strain 2774:2779 the ktr3Δ cap6Δ strain 2758:2779 the ktr3Δ cap6Δ strain 2758:2779 Furthermore, the ktr3Δ cap6Δ strain is completely avirulent in a mouse infection model. 36409123 16 100 from model 2826:2830 arg1 avirulent 2795:2803 avirulent 2795:2803 avirulent 2795:2803 Furthermore, the ktr3Δ cap6Δ strain is completely avirulent in a mouse infection model. 36409123 7 101 theme cryptococcosis 1376:1389 arg1 model 1367:1371 a mouse model 1359:1371 a mouse model of cryptococcosis 1359:1389 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 11 102 theme Cryptococcus 1991:2002 arg1 neoformans 2004:2013 Cryptococcus neoformans 1991:2013 IMPORTANCE Cryptococcus neoformans 1980:2013 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 0 103 theme Cryptococcus 140:151 arg1 neoformans 153:162 Cryptococcus neoformans 140:162 Cryptococcus neoformans 140:162 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 14 104 dep C. 2490:2491 arg1 neoformans 2493:2502 neoformans 2493:2502 neoformans 2493:2502 We also identified two novel C. neoformans stress sensors that require Ktr3- and Cap6-mediated posttranslational modification for full function. 36409123 9 105 theme ergosterol 1723:1732 arg1 induction 1656:1664 reduced induction 1648:1664 reduced induction of the host immune response 1648:1692 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 9 105 theme ergosterol 1723:1732 arg1 trafficking 1708:1718 defective trafficking 1698:1718 defective trafficking of ergosterol, an immunoreactive fungal molecule 1698:1767 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 18 106 dep are 3020:3022 arg1 targets 3030:3036 novel targets 3024:3036 novel targets for antifungal therapy 3024:3059 As there are no human homologs for Cap6 or Ktr3, these fungus-specific mannosyltransferases are novel targets for antifungal therapy. 36409123 6 107 theme integrity 1224:1232 arg1 pathway 1240:1246 the Mpk1-dependent cell wall integrity (CWI) pathway 1195:1246 the Mpk1-dependent cell wall integrity (CWI) pathway 1195:1246 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 11 108 contain containing 2170:2179 arg1 O-glycans 2160:2168 minor O-glycans 2154:2168 minor O-glycans containing xylose 2154:2186 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 11 108 contain containing 2170:2179 arg2 xylose 2181:2186 xylose 2181:2186 xylose 2181:2186 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 3 109 theme Cap6-mediated 625:637 arg1 O-mannosylation 668:682 Cap6-mediated minor or Ktr3-mediated major O-mannosylation 625:682 Cap6-mediated minor or Ktr3-mediated major O-mannosylation 625:682 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 11 110 theme abundant 2089:2096 arg1 proteins 2070:2077 its surface proteins 2058:2077 its surface proteins 2058:2077 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 11 110 theme abundant 2089:2096 arg1 O-glycans 2104:2112 the more abundant major O-glycans 2080:2112 the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose 2080:2186 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 8 111 theme lung 1483:1486 arg1 cells 1499:1503 lung epithelial cells 1483:1503 lung epithelial cells 1483:1503 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 6 112 theme cell 1214:1217 arg1 CWI 1235:1237 CWI 1235:1237 CWI 1235:1237 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 6 112 theme cell 1214:1217 arg1 integrity 1224:1232 Mpk1-dependent cell wall integrity 1199:1232 the Mpk1-dependent cell wall integrity (CWI) pathway 1195:1246 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 5 113 theme wml1Δ 1055:1059 arg1 strains 1067:1073 both ktr3Δ cap6Δ and wml1Δ wml2Δ strains 1034:1073 strains 1067:1073 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 9 114 theme fungal 1753:1758 arg1 molecule 1760:1767 an immunoreactive fungal molecule 1735:1767 an immunoreactive fungal molecule 1735:1767 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 9 114 theme fungal 1753:1758 arg1 ergosterol 1723:1732 ergosterol 1723:1732 ergosterol 1723:1732 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 4 115 theme double 703:708 arg1 deletion 710:717 The double deletion 699:717 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) 699:748 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 0 116 theme Cell 75:78 arg1 Integrity 85:93 Cell Wall Integrity 75:93 Cell Wall Integrity Signaling 75:103 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 17 117 theme critical 2869:2876 arg1 roles 2878:2882 critical roles 2869:2882 critical roles for O-glycosylation in fungal pathogenesis 2869:2925 Together, these results demonstrate critical roles for O-glycosylation in fungal pathogenesis. 36409123 0 118 theme Integrity 85:93 arg1 Signaling 95:103 Cell Wall Integrity Signaling 75:103 Cell Wall Integrity Signaling 75:103 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 5 119 theme Mpk1 964:967 arg1 MAPK 1003:1006 MAPK 1003:1006 MAPK 1003:1006 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 5 119 theme Mpk1 964:967 arg1 kinase 995:1000 Mpk1 mitogen-activated protein kinase 964:1000 the Mpk1 mitogen-activated protein kinase (MAPK) 960:1007 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 11 120 theme glycans 2047:2053 arg1 types 2029:2033 two types 2025:2033 two types of O-linked glycans 2025:2053 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 12 121 theme α1,3-mannosyltransferase 2231:2254 arg1 role 2214:2217 the role 2210:2217 the role of the Cap6 α1,3-mannosyltransferase in the synthesis of minor O-glycans 2210:2290 Here, we demonstrate the role of the Cap6 α1,3-mannosyltransferase in the synthesis of minor O-glycans. 36409123 0 122 dep Signaling 95:103 arg1 Pathogenesis 164:175 Pathogenesis 164:175 Pathogenesis 164:175 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 12 123 theme Cap6 2226:2229 arg1 α1,3-mannosyltransferase 2231:2254 the Cap6 α1,3-mannosyltransferase 2222:2254 the Cap6 α1,3-mannosyltransferase 2222:2254 Here, we demonstrate the role of the Cap6 α1,3-mannosyltransferase in the synthesis of minor O-glycans. 36409123 6 124 theme cap6Δ 1113:1117 arg1 strain 1119:1124 the ktr3Δ cap6Δ strain 1103:1124 the ktr3Δ cap6Δ strain 1103:1124 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 5 125 theme protein 987:993 arg1 MAPK 1003:1006 MAPK 1003:1006 MAPK 1003:1006 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 5 125 theme protein 987:993 arg1 kinase 995:1000 Mpk1 mitogen-activated protein kinase 964:1000 the Mpk1 mitogen-activated protein kinase (MAPK) 960:1007 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 7 126 from avirulent 1346:1354 arg1 model 1367:1371 a mouse model 1359:1371 a mouse model of cryptococcosis 1359:1389 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 6 127 theme Transcriptome 1076:1088 arg1 profiling 1090:1098 Transcriptome profiling 1076:1098 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment 1076:1142 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 12 128 theme O-glycans 2282:2290 arg1 synthesis 2263:2271 the synthesis 2259:2271 the synthesis of minor O-glycans 2259:2290 Here, we demonstrate the role of the Cap6 α1,3-mannosyltransferase in the synthesis of minor O-glycans. 36409123 2 129 theme responsible 412:422 arg1 α1,3-mannosyltransferase 387:410 an α1,3-mannosyltransferase 384:410 an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus 384:514 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 5 130 theme -induced 932:939 arg1 phosphorylation 941:955 Tunicamycin (TM)-induced phosphorylation 916:955 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) 916:1007 Tunicamycin (TM)-induced phosphorylation of the Mpk1 mitogen-activated protein kinase (MAPK) was greatly decreased in both ktr3Δ cap6Δ and wml1Δ wml2Δ strains. 36409123 10 131 with resistance 1919:1928 arg1 cells 1956:1960 host cells 1951:1960 host cells 1951:1960 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 11 132 theme surface 2062:2068 arg1 proteins 2070:2077 its surface proteins 2058:2077 its surface proteins 2058:2077 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 11 132 theme surface 2062:2068 arg1 O-glycans 2104:2112 the more abundant major O-glycans 2080:2112 the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose 2080:2186 IMPORTANCE Cryptococcus neoformans assembles two types of O-linked glycans on its surface proteins, the more abundant major O-glycans that do not contain xylose residues and minor O-glycans containing xylose. 36409123 0 133 theme Mannosylation 22:34 arg1 Extension 0:8 Extension 0:8 Extension of O-Linked Mannosylation in the Golgi Apparatus 0:57 Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis. 36409123 13 134 theme related 2373:2379 arg1 α1,2-mannosyltransferase 2386:2409 the related Ktr3 α1,2-mannosyltransferase 2369:2409 the related Ktr3 α1,2-mannosyltransferase 2369:2409 Previously proposed to be involved in capsule biosynthesis, Cap6 works with the related Ktr3 α1,2-mannosyltransferase to synthesize O-glycans on their target proteins. 36409123 13 135 theme target 2444:2449 arg1 proteins 2451:2458 their target proteins 2438:2458 their target proteins 2438:2458 Previously proposed to be involved in capsule biosynthesis, Cap6 works with the related Ktr3 α1,2-mannosyltransferase to synthesize O-glycans on their target proteins. 36409123 7 136 from model 1367:1371 arg1 avirulent 1346:1354 avirulent 1346:1354 avirulent 1346:1354 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 7 136 from model 1367:1371 arg1 strain 1335:1340 the ktr3Δ cap6Δ strain 1319:1340 the ktr3Δ cap6Δ strain 1319:1340 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 10 137 with interaction 1934:1944 arg1 cells 1956:1960 host cells 1951:1960 host cells 1951:1960 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 3 138 theme major 662:666 arg1 O-mannosylation 668:682 Cap6-mediated minor or Ktr3-mediated major O-mannosylation 625:682 Cap6-mediated minor or Ktr3-mediated major O-mannosylation 625:682 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 2 139 dep C. 350:351 arg1 neoformans 353:362 neoformans 353:362 neoformans 353:362 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 2 140 theme mannose 439:445 arg1 addition 447:454 the second mannose addition 428:454 the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus 428:514 In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor O-glycans containing xylose in the Golgi apparatus. 36409123 10 141 from extension 1794:1802 arg1 apparatus 1817:1825 the Golgi apparatus 1807:1825 the Golgi apparatus 1807:1825 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 14 142 theme full 2591:2594 arg1 function 2596:2603 full function 2591:2603 full function 2591:2603 We also identified two novel C. neoformans stress sensors that require Ktr3- and Cap6-mediated posttranslational modification for full function. 36409123 7 143 theme several 1292:1298 arg1 conditions 1307:1316 several stress conditions 1292:1316 several stress conditions 1292:1316 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 7 144 theme cap6Δ 1329:1333 arg1 avirulent 1346:1354 avirulent 1346:1354 avirulent 1346:1354 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 7 144 theme cap6Δ 1329:1333 arg1 strain 1335:1340 the ktr3Δ cap6Δ strain 1319:1340 the ktr3Δ cap6Δ strain 1319:1340 Consistent with its defective growth under several stress conditions, the ktr3Δ cap6Δ strain was avirulent in a mouse model of cryptococcosis. 36409123 8 145 theme blood-brain 1582:1592 arg1 BBB 1603:1605 BBB 1603:1605 BBB 1603:1605 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 8 145 theme blood-brain 1582:1592 arg1 barrier 1594:1600 the blood-brain barrier 1578:1600 the blood-brain barrier (BBB) 1578:1606 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 10 146 theme various 1851:1857 arg1 interaction 1934:1944 interaction 1934:1944 interaction with host cells in C. neoformans 1934:1977 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 10 146 theme various 1851:1857 arg1 signaling 1898:1906 CWI signaling 1894:1906 CWI signaling 1894:1906 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 10 146 theme various 1851:1857 arg1 processes 1875:1883 various pathobiological processes 1851:1883 various pathobiological processes 1851:1883 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 10 146 theme various 1851:1857 arg1 resistance 1919:1928 stress resistance 1912:1928 stress resistance 1912:1928 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 4 147 theme O-glycans 816:824 arg1 position 804:811 the second position 793:811 the second position of O-glycans 793:824 The double deletion of KTR3 and CAP6 (ktr3Δ cap6Δ) completely blocked the mannose addition at the second position of O-glycans, resulting in the accumulation of proteins with O-glycans carrying only a single mannose. 36409123 6 148 theme TM 1131:1132 arg1 treatment 1134:1142 TM treatment 1131:1142 TM treatment 1131:1142 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 10 149 theme CWI 1894:1896 arg1 signaling 1898:1906 CWI signaling 1894:1906 CWI signaling 1894:1906 In conclusion, O-glycan extension in the Golgi apparatus plays critical roles in various pathobiological processes, such as CWI signaling and stress resistance and interaction with host cells in C. neoformans. 36409123 15 150 from defects 2674:2680 arg1 trafficking 2732:2742 ergosterol trafficking 2721:2742 ergosterol trafficking 2721:2742 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 15 150 from defects 2674:2680 arg1 CWI 2712:2714 CWI 2712:2714 CWI 2712:2714 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 15 150 from defects 2674:2680 arg1 pathways 2702:2709 stress signaling pathways 2685:2709 stress signaling pathways 2685:2709 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 15 151 theme mutant 2651:2656 arg1 strain 2658:2663 the ktr3Δ cap6Δ double O-glycan mutant strain 2619:2663 the ktr3Δ cap6Δ double O-glycan mutant strain 2619:2663 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 3 152 theme cell 521:524 arg1 Wml2 576:579 Wml2 576:579 Wml2 576:579 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 3 152 theme cell 521:524 arg1 Wml1 551:554 Wml1 551:554 Wml1 (WSC/Mid2-like) 551:570 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 3 152 theme cell 521:524 arg1 proteins 541:548 Two cell surface sensor proteins 517:548 Two cell surface sensor proteins 517:548 Two cell surface sensor proteins, Wml1 (WSC/Mid2-like) and Wml2, were found to be independent substrates of Cap6-mediated minor or Ktr3-mediated major O-mannosylation, respectively. 36409123 15 153 theme double 2635:2640 arg1 strain 2658:2663 the ktr3Δ cap6Δ double O-glycan mutant strain 2619:2663 the ktr3Δ cap6Δ double O-glycan mutant strain 2619:2663 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 13 154 theme Ktr3 2381:2384 arg1 α1,2-mannosyltransferase 2386:2409 the related Ktr3 α1,2-mannosyltransferase 2369:2409 the related Ktr3 α1,2-mannosyltransferase 2369:2409 Previously proposed to be involved in capsule biosynthesis, Cap6 works with the related Ktr3 α1,2-mannosyltransferase to synthesize O-glycans on their target proteins. 36409123 14 155 theme Cap6-mediated 2542:2554 arg1 modification 2574:2585 Cap6-mediated posttranslational modification 2542:2585 Cap6-mediated posttranslational modification 2542:2585 We also identified two novel C. neoformans stress sensors that require Ktr3- and Cap6-mediated posttranslational modification for full function. 36409123 6 156 theme strain 1119:1124 arg1 profiling 1090:1098 Transcriptome profiling 1076:1098 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment 1076:1142 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 8 157 theme virulence 1413:1421 arg1 defect 1423:1428 this virulence defect 1408:1428 this virulence defect 1408:1428 Associated with this virulence defect, the ktr3Δ cap6Δ strain showed decreased adhesion to lung epithelial cells, decreased proliferation within macrophages, and reduced transcytosis of the blood-brain barrier (BBB). 36409123 15 158 theme ktr3Δ 2623:2627 arg1 strain 2658:2663 the ktr3Δ cap6Δ double O-glycan mutant strain 2619:2663 the ktr3Δ cap6Δ double O-glycan mutant strain 2619:2663 Accordingly, the ktr3Δ cap6Δ double O-glycan mutant strain displays defects in stress signaling pathways, CWI, and ergosterol trafficking. 36409123 18 159 theme novel 3024:3028 arg1 targets 3030:3036 novel targets 3024:3036 novel targets for antifungal therapy 3024:3059 As there are no human homologs for Cap6 or Ktr3, these fungus-specific mannosyltransferases are novel targets for antifungal therapy. 36409123 9 160 theme ktr3Δ 1622:1626 arg1 strain 1634:1639 the ktr3Δ cap6Δ strain 1618:1639 the ktr3Δ cap6Δ strain 1618:1639 Notably, the ktr3Δ cap6Δ strain showed reduced induction of the host immune response and defective trafficking of ergosterol, an immunoreactive fungal molecule. 36409123 6 161 theme ktr3Δ 1107:1111 arg1 strain 1119:1124 the ktr3Δ cap6Δ strain 1103:1124 the ktr3Δ cap6Δ strain 1103:1124 Transcriptome profiling of the ktr3Δ cap6Δ strain upon TM treatment revealed decreased expression of genes involved in the Mpk1-dependent cell wall integrity (CWI) pathway. 36409123 1 162 theme glycans 261:267 arg1 types 243:247 two types 239:247 two types of O-linked glycans 239:267 The human-pathogenic yeast Cryptococcus neoformans assembles two types of O-linked glycans on its proteins. 37007511 2 0 dep ration 531:536 arg1 1 502:502 1 502:502 1 502:502 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 1 dep TMR 625:627 arg1 3 612:612 3 612:612 3 612:612 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 11 2 from abundance 1652:1660 arg1 groups 1685:1690 the F-CSM and F-RSM groups 1665:1690 the F-CSM and F-RSM groups 1665:1690 Prevotella was greater in relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 8 3 theme CK 1347:1348 arg1 groups 1360:1365 the CK and F-RSM groups 1343:1365 the CK and F-RSM groups 1343:1365 The relative abundance of Bacteroidetes was greater in the CK and F-RSM groups compared to the F-CSM group (p < 0.05). 37007511 10 4 theme F-RSM 1571:1575 arg1 groups 1577:1582 the F-CSM and F-RSM groups 1557:1582 groups 1577:1582 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 2 5 with ration 531:536 arg1 TMR 625:627 (3) fermented TMR 611:627 (3) fermented TMR containing RSM (F-RSM group) 611:656 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 5 with ration 531:536 arg1 TMR 573:575 (2) fermented TMR 559:575 (2) fermented TMR containing CSM (F-CSM group) 559:604 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 5 with ration 531:536 arg1 CK 554:555 CK 554:555 CK 554:555 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 5 with ration 531:536 arg1 SBM 549:551 SBM 549:551 SBM (CK) 549:556 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 5 6 theme greater 969:975 arg1 amounts 977:983 greater amounts 969:983 greater amounts of volatile fatty acids (VFA) 969:1013 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 6 theme greater 969:975 arg1 VFA 1010:1012 VFA 1010:1012 VFA 1010:1012 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 6 theme greater 969:975 arg1 acids 1003:1007 volatile fatty acids 988:1007 volatile fatty acids 988:1007 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 11 7 theme CK 1704:1705 arg1 p < 0.05 1714:1721 p < 0.05 1714:1721 p < 0.05 1714:1721 Prevotella was greater in relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 11 7 theme CK 1704:1705 arg1 group 1707:1711 the CK group 1700:1711 the CK group (p < 0.05) 1700:1722 Prevotella was greater in relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 8 8 theme F-RSM 1354:1358 arg1 groups 1360:1365 the CK and F-RSM groups 1343:1365 the CK and F-RSM groups 1343:1365 The relative abundance of Bacteroidetes was greater in the CK and F-RSM groups compared to the F-CSM group (p < 0.05). 37007511 15 9 theme Hu 2263:2264 arg1 sheep 2266:2270 Hu sheep 2263:2270 Hu sheep 2263:2270 Replacement of SBM with F-CSM increased VFA yield and further promoted the performance of Hu sheep. 37007511 7 10 theme F-CSM 1181:1185 arg1 group 1187:1191 The F-CSM group 1177:1191 The F-CSM group 1177:1191 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 12 11 theme Veillonellaceae_UCG-001 1752:1774 arg1 abundances 1738:1747 The relative abundances 1725:1747 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 1725:1802 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 correlated with rumen butyric acid content and NH3-N content (p < 0.05). 37007511 10 12 located present 1515:1521 arg2 Prevotella 1500:1509 Prevotella 1500:1509 Prevotella 1500:1509 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 10 12 located present 1515:1521 arg1 abundance 1544:1552 a higher relative abundance 1526:1552 a higher relative abundance in the F-CSM and F-RSM groups 1526:1582 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 13 13 theme sheep 1968:1972 arg1 diet 1957:1960 the diet 1953:1960 the diet of Hu sheep 1953:1972 Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism. 37007511 12 14 theme Lachnospiraceae_XPB1014 1780:1802 arg1 abundances 1738:1747 The relative abundances 1725:1747 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 1725:1802 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 correlated with rumen butyric acid content and NH3-N content (p < 0.05). 37007511 10 15 attach present 1515:1521 arg2 Prevotella 1500:1509 Prevotella 1500:1509 Prevotella 1500:1509 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 10 15 attach present 1515:1521 arg1 abundance 1544:1552 a higher relative abundance 1526:1552 a higher relative abundance in the F-CSM and F-RSM groups 1526:1582 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 4 16 theme daily 761:765 arg1 gain 767:770 average daily gain 753:770 average daily gain 753:770 In terms of average daily gain, the F-RSM group outperformed the CK and F-CSM groups (p < 0.05). 37007511 2 17 theme F-RSM 645:649 arg1 RSM 640:642 RSM 640:642 RSM (F-RSM group) 640:656 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 17 theme F-RSM 645:649 arg1 group 651:655 F-RSM group 645:655 F-RSM group 645:655 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 0 18 theme bacterial 114:122 arg1 composition 124:134 bacterial composition 114:134 bacterial composition 114:134 Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep. 37007511 1 19 theme bacterial 325:333 arg1 composition 335:345 bacterial composition 325:345 bacterial composition 325:345 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 14 20 contain has 2076:2078 arg2 influence 2083:2091 an influence 2080:2091 an influence on the richness and diversity of rumen bacteria at the phylum and genus levels 2080:2170 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 14 20 contain has 2076:2078 arg1 replacement 2037:2047 The replacement 2033:2047 The replacement of F-CSM and F-RSM for SBM 2033:2074 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 0 21 from performance 77:87 arg1 sheep 142:146 Hu sheep 139:146 Hu sheep 139:146 Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep. 37007511 3 22 theme matter 699:704 arg1 intake 685:690 The three groups' intake 667:690 The three groups' intake of dry matter 667:704 Results The three groups' intake of dry matter differed significantly (p < 0.05). 37007511 3 23 dep Results 659:665 arg1 differed 706:713 differed 706:713 differed significantly (p < 0.05) 706:738 Results The three groups' intake of dry matter differed significantly (p < 0.05). 37007511 14 24 from levels 2165:2170 arg1 diversity 2113:2121 diversity 2113:2121 diversity 2113:2121 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 14 24 from levels 2165:2170 arg1 richness 2100:2107 richness 2100:2107 richness 2100:2107 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 2 25 theme total 519:523 arg1 TMR 539:541 TMR 539:541 TMR 539:541 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 25 theme total 519:523 arg1 ration 531:536 total mixed ration 519:536 three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group) 483:656 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 26 dep TMR 573:575 arg1 2 560:560 2 560:560 2 560:560 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 9 27 theme other 1428:1432 arg1 groups 1434:1439 the other groups 1424:1439 the other groups 1424:1439 In comparison to the other groups, Firmicutes were less abundant in the CK group (p < 0.05). 37007511 4 28 theme CK 806:807 arg1 p < 0.05 827:834 p < 0.05 827:834 p < 0.05 827:834 In terms of average daily gain, the F-RSM group outperformed the CK and F-CSM groups (p < 0.05). 37007511 4 28 theme CK 806:807 arg1 groups 819:824 the CK and F-CSM groups 802:824 the CK and F-CSM groups (p < 0.05) 802:835 In terms of average daily gain, the F-RSM group outperformed the CK and F-CSM groups (p < 0.05). 37007511 5 29 theme F-CSM 910:914 arg1 p < 0.05 934:941 p < 0.05 934:941 p < 0.05 934:941 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 29 theme F-CSM 910:914 arg1 groups 926:931 the F-CSM and F-RSM groups 906:931 groups 926:931 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 2 30 theme origins 449:455 arg1 weights 410:416 starting body weights 396:416 starting body weights of 22.51 ± 2.84 kg and similar origins 396:455 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 1 31 theme soybean 257:263 arg1 SBM 271:273 SBM 271:273 SBM 271:273 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 1 31 theme soybean 257:263 arg1 meal 265:268 soybean meal 257:268 soybean meal (SBM) 257:274 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 5 32 theme F-RSM 920:924 arg1 p < 0.05 934:941 p < 0.05 934:941 p < 0.05 934:941 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 32 theme F-RSM 920:924 arg1 groups 926:931 the F-CSM and F-RSM groups 906:931 groups 926:931 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 13 33 with SBM 1926:1928 arg1 F-CSM 1935:1939 F-CSM 1935:1939 F-CSM 1935:1939 Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism. 37007511 13 33 with SBM 1926:1928 arg1 F-RSM 1944:1948 F-RSM 1944:1948 F-RSM 1944:1948 Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism. 37007511 4 34 theme F-RSM 777:781 arg1 group 783:787 the F-RSM group 773:787 the F-RSM group 773:787 In terms of average daily gain, the F-RSM group outperformed the CK and F-CSM groups (p < 0.05). 37007511 0 35 theme Hu 139:140 arg1 sheep 142:146 Hu sheep 139:146 Hu sheep 139:146 Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep. 37007511 6 36 theme crude 1090:1094 arg1 yield 1104:1108 the microbial crude protein yield 1076:1108 the microbial crude protein yield 1076:1108 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 6 36 theme crude 1090:1094 arg1 higher 1128:1133 higher 1128:1133 higher 1128:1133 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 1 37 theme rumen 301:305 arg1 fermentation 307:318 rumen fermentation 301:318 rumen fermentation 301:318 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 2 38 theme body 405:408 arg1 weights 410:416 starting body weights 396:416 starting body weights of 22.51 ± 2.84 kg and similar origins 396:455 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 1 39 dep Background 149:158 arg1 examined 171:178 examined 171:178 examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition 171:345 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 0 40 theme Fermented 0:8 arg1 meals 34:38 Fermented cottonseed and rapeseed meals 0:38 Fermented cottonseed and rapeseed meals 0:38 Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep. 37007511 9 41 dep groups 1434:1439 arg1 comparison 1410:1419 comparison 1410:1419 comparison 1410:1419 In comparison to the other groups, Firmicutes were less abundant in the CK group (p < 0.05). 37007511 2 42 theme fermented 563:571 arg1 TMR 573:575 (2) fermented TMR 559:575 (2) fermented TMR containing CSM (F-CSM group) 559:604 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 13 43 theme function 1882:1889 arg1 prediction 1891:1900 Gene function prediction 1877:1900 Gene function prediction 1877:1900 Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism. 37007511 2 44 theme Hu 382:383 arg1 sheep 385:389 51 four-month-old indigenous male Hu sheep 348:389 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins 348:455 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 6 45 theme F-RSM 1152:1156 arg1 groups 1158:1163 the F-CSM and F-RSM groups 1138:1163 the F-CSM and F-RSM groups (p < 0.05) 1138:1174 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 6 45 theme F-RSM 1152:1156 arg1 p < 0.05 1166:1173 p < 0.05 1166:1173 p < 0.05 1166:1173 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 5 46 theme F-CSM 953:957 arg1 group 959:963 the F-CSM group 949:963 the F-CSM group 949:963 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 7 47 theme enzyme 1260:1265 arg1 p < 0.05 1277:1284 p < 0.05 1277:1284 p < 0.05 1277:1284 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 47 theme enzyme 1260:1265 arg1 activity 1267:1274 cellulose enzyme activity 1250:1274 cellulose enzyme activity (p < 0.05) 1250:1285 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 10 48 from present 1515:1521 arg1 abundance 1544:1552 a higher relative abundance 1526:1552 a higher relative abundance in the F-CSM and F-RSM groups 1526:1582 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 10 49 theme higher 1528:1533 arg1 abundance 1544:1552 a higher relative abundance 1526:1552 a higher relative abundance in the F-CSM and F-RSM groups 1526:1582 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 2 50 theme indigenous 366:375 arg1 sheep 385:389 51 four-month-old indigenous male Hu sheep 348:389 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins 348:455 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 6 51 theme F-CSM 1142:1146 arg1 groups 1158:1163 the F-CSM and F-RSM groups 1138:1163 the F-CSM and F-RSM groups (p < 0.05) 1138:1174 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 6 51 theme F-CSM 1142:1146 arg1 p < 0.05 1166:1173 p < 0.05 1166:1173 p < 0.05 1166:1173 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 9 52 from abundant 1463:1470 arg1 p < 0.05 1489:1496 p < 0.05 1489:1496 p < 0.05 1489:1496 In comparison to the other groups, Firmicutes were less abundant in the CK group (p < 0.05). 37007511 9 52 from abundant 1463:1470 arg1 group 1482:1486 the CK group 1475:1486 the CK group (p < 0.05) 1475:1497 In comparison to the other groups, Firmicutes were less abundant in the CK group (p < 0.05). 37007511 12 53 theme NH3-N 1851:1855 arg1 p < 0.05 1866:1873 p < 0.05 1866:1873 p < 0.05 1866:1873 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 correlated with rumen butyric acid content and NH3-N content (p < 0.05). 37007511 12 53 theme NH3-N 1851:1855 arg1 content 1857:1863 NH3-N content 1851:1863 NH3-N content (p < 0.05) 1851:1874 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 correlated with rumen butyric acid content and NH3-N content (p < 0.05). 37007511 0 54 theme soybean 51:57 arg1 meal 59:62 soybean meal 51:62 soybean meal 51:62 Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep. 37007511 1 55 theme Hu 279:280 arg1 performance 288:298 Hu sheep performance 279:298 Hu sheep performance 279:298 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 14 56 theme phylum 2148:2153 arg1 levels 2165:2170 the phylum and genus levels 2144:2170 levels 2165:2170 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 14 57 theme genus 2159:2163 arg1 levels 2165:2170 the phylum and genus levels 2144:2170 levels 2165:2170 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 5 58 theme volatile 988:995 arg1 acids 1003:1007 volatile fatty acids 988:1007 volatile fatty acids 988:1007 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 7 59 theme F-RSM 1224:1228 arg1 p < 0.05 1277:1284 p < 0.05 1277:1284 p < 0.05 1277:1284 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 59 theme F-RSM 1224:1228 arg1 pepsin 1239:1244 pepsin 1239:1244 pepsin 1239:1244 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 59 theme F-RSM 1224:1228 arg1 group 1230:1234 the F-RSM group 1220:1234 the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05) 1220:1285 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 59 theme F-RSM 1224:1228 arg1 activity 1267:1274 cellulose enzyme activity 1250:1274 cellulose enzyme activity (p < 0.05) 1250:1285 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 8 60 theme Bacteroidetes 1314:1326 arg1 greater 1332:1338 greater 1332:1338 greater 1332:1338 The relative abundance of Bacteroidetes was greater in the CK and F-RSM groups compared to the F-CSM group (p < 0.05). 37007511 8 60 theme Bacteroidetes 1314:1326 arg1 abundance 1301:1309 The relative abundance 1288:1309 The relative abundance of Bacteroidetes 1288:1326 The relative abundance of Bacteroidetes was greater in the CK and F-RSM groups compared to the F-CSM group (p < 0.05). 37007511 12 61 theme butyric 1826:1832 arg1 acid 1834:1837 rumen butyric acid 1820:1837 rumen butyric acid content 1820:1845 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 correlated with rumen butyric acid content and NH3-N content (p < 0.05). 37007511 5 62 theme acids 1003:1007 arg1 amounts 977:983 greater amounts 969:983 greater amounts of volatile fatty acids (VFA) 969:1013 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 62 theme acids 1003:1007 arg1 VFA 1010:1012 VFA 1010:1012 VFA 1010:1012 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 62 theme acids 1003:1007 arg1 acids 1003:1007 volatile fatty acids 988:1007 volatile fatty acids 988:1007 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 15 63 with Replacement 2173:2183 arg1 F-CSM 2197:2201 F-CSM 2197:2201 F-CSM 2197:2201 Replacement of SBM with F-CSM increased VFA yield and further promoted the performance of Hu sheep. 37007511 4 64 theme F-CSM 813:817 arg1 p < 0.05 827:834 p < 0.05 827:834 p < 0.05 827:834 In terms of average daily gain, the F-RSM group outperformed the CK and F-CSM groups (p < 0.05). 37007511 4 64 theme F-CSM 813:817 arg1 groups 819:824 the CK and F-CSM groups 802:824 the CK and F-CSM groups (p < 0.05) 802:835 In terms of average daily gain, the F-RSM group outperformed the CK and F-CSM groups (p < 0.05). 37007511 8 65 theme F-CSM 1383:1387 arg1 group 1389:1393 the F-CSM group 1379:1393 the F-CSM group (p < 0.05) 1379:1404 The relative abundance of Bacteroidetes was greater in the CK and F-RSM groups compared to the F-CSM group (p < 0.05). 37007511 8 65 theme F-CSM 1383:1387 arg1 p < 0.05 1396:1403 p < 0.05 1396:1403 p < 0.05 1396:1403 The relative abundance of Bacteroidetes was greater in the CK and F-RSM groups compared to the F-CSM group (p < 0.05). 37007511 1 66 theme rapeseed 233:240 arg1 meal 242:245 rapeseed meal 233:245 rapeseed meal (RSM) 233:251 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 1 66 theme rapeseed 233:240 arg1 RSM 248:250 RSM 248:250 RSM 248:250 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 13 67 from SBM 1926:1928 arg1 diet 1957:1960 the diet 1953:1960 the diet of Hu sheep 1953:1972 Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism. 37007511 10 68 from abundance 1544:1552 arg1 groups 1577:1582 the F-CSM and F-RSM groups 1557:1582 groups 1577:1582 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 10 68 from abundance 1544:1552 arg1 present 1515:1521 present 1515:1521 present 1515:1521 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 10 69 theme CK 1596:1597 arg1 p < 0.05 1606:1613 p < 0.05 1606:1613 p < 0.05 1606:1613 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 10 69 theme CK 1596:1597 arg1 group 1599:1603 the CK group 1592:1603 the CK group (p < 0.05) 1592:1614 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 11 70 theme relative 1643:1650 arg1 abundance 1652:1660 relative abundance 1643:1660 relative abundance in the F-CSM and F-RSM groups 1643:1690 Prevotella was greater in relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 15 71 theme sheep 2266:2270 arg1 performance 2248:2258 the performance 2244:2258 the performance of Hu sheep 2244:2270 Replacement of SBM with F-CSM increased VFA yield and further promoted the performance of Hu sheep. 37007511 13 72 theme Hu 1965:1966 arg1 sheep 1968:1972 Hu sheep 1965:1972 Hu sheep 1965:1972 Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism. 37007511 9 73 from group 1482:1486 arg1 abundant 1463:1470 abundant 1463:1470 abundant 1463:1470 In comparison to the other groups, Firmicutes were less abundant in the CK group (p < 0.05). 37007511 2 74 theme fermented 615:623 arg1 TMR 625:627 (3) fermented TMR 611:627 (3) fermented TMR containing RSM (F-RSM group) 611:656 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 11 75 theme F-RSM 1679:1683 arg1 groups 1685:1690 the F-CSM and F-RSM groups 1665:1690 the F-CSM and F-RSM groups 1665:1690 Prevotella was greater in relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 5 76 contain had 965:967 arg2 VFA 1010:1012 VFA 1010:1012 VFA 1010:1012 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 76 contain had 965:967 arg2 acids 1003:1007 volatile fatty acids 988:1007 volatile fatty acids 988:1007 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 76 contain had 965:967 arg2 amounts 977:983 greater amounts 969:983 greater amounts of volatile fatty acids (VFA) 969:1013 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 76 contain had 965:967 arg1 group 959:963 the F-CSM group 949:963 the F-CSM group 949:963 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 11 77 theme F-CSM 1669:1673 arg1 groups 1685:1690 the F-CSM and F-RSM groups 1665:1690 the F-CSM and F-RSM groups 1665:1690 Prevotella was greater in relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 4 78 theme average 753:759 arg1 gain 767:770 average daily gain 753:770 average daily gain 753:770 In terms of average daily gain, the F-RSM group outperformed the CK and F-CSM groups (p < 0.05). 37007511 6 79 theme CK 1066:1067 arg1 group 1069:1073 the CK group 1062:1073 the CK group 1062:1073 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 1 80 theme cottonseed 208:217 arg1 CSM 225:227 CSM 225:227 CSM 225:227 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 1 80 theme cottonseed 208:217 arg1 meal 219:222 cottonseed meal 208:222 cottonseed meal (CSM) 208:228 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 4 81 theme gain 767:770 arg1 terms 744:748 terms 744:748 terms of average daily gain 744:770 In terms of average daily gain, the F-RSM group outperformed the CK and F-CSM groups (p < 0.05). 37007511 12 82 theme relative 1729:1736 arg1 abundances 1738:1747 The relative abundances 1725:1747 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 1725:1802 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 correlated with rumen butyric acid content and NH3-N content (p < 0.05). 37007511 2 83 contain containing 577:586 arg2 CSM 588:590 CSM 588:590 CSM (F-CSM group) 588:604 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 83 contain containing 577:586 arg1 TMR 573:575 (2) fermented TMR 559:575 (2) fermented TMR containing CSM (F-CSM group) 559:604 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 83 contain containing 577:586 arg2 group 599:603 F-CSM group 593:603 F-CSM group 593:603 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 5 84 theme CK 889:890 arg1 group 892:896 the CK group 885:896 the CK group 885:896 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 2 85 with sheep 385:389 arg1 weights 410:416 starting body weights 396:416 starting body weights of 22.51 ± 2.84 kg and similar origins 396:455 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 6 86 dep group 1069:1073 arg1 comparison 1048:1057 comparison 1048:1057 comparison 1048:1057 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 2 87 theme mixed 525:529 arg1 TMR 539:541 TMR 539:541 TMR 539:541 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 87 theme mixed 525:529 arg1 ration 531:536 total mixed ration 519:536 three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group) 483:656 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 88 theme F-CSM 593:597 arg1 group 599:603 F-CSM group 593:603 F-CSM group 593:603 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 88 theme F-CSM 593:597 arg1 CSM 588:590 CSM 588:590 CSM (F-CSM group) 588:604 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 5 89 theme F-RSM 1024:1028 arg1 groups 1037:1042 the F-RSM and CK groups 1020:1042 groups 1037:1042 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 90 theme rumen 852:856 arg1 pH 842:843 The pH 838:843 The pH of the rumen 838:856 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 5 90 theme rumen 852:856 arg1 lower 876:880 lower 876:880 lower 876:880 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 2 91 theme non-fermented 505:517 arg1 TMR 539:541 TMR 539:541 TMR 539:541 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 91 theme non-fermented 505:517 arg1 ration 531:536 total mixed ration 519:536 three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group) 483:656 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 0 92 from fermentation 96:107 arg1 sheep 142:146 Hu sheep 139:146 Hu sheep 139:146 Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep. 37007511 5 93 theme CK 1034:1035 arg1 groups 1037:1042 the F-RSM and CK groups 1020:1042 groups 1037:1042 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 1 94 from effects 184:190 arg1 performance 288:298 Hu sheep performance 279:298 Hu sheep performance 279:298 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 1 94 from effects 184:190 arg1 fermentation 307:318 rumen fermentation 301:318 rumen fermentation 301:318 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 1 94 from effects 184:190 arg1 composition 335:345 bacterial composition 325:345 bacterial composition 325:345 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 3 95 theme dry 695:697 arg1 matter 699:704 dry matter 695:704 dry matter 695:704 Results The three groups' intake of dry matter differed significantly (p < 0.05). 37007511 0 96 theme rumen 90:94 arg1 fermentation 96:107 rumen fermentation 90:107 rumen fermentation 90:107 Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep. 37007511 1 97 theme sheep 282:286 arg1 performance 288:298 Hu sheep performance 279:298 Hu sheep performance 279:298 Background This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 37007511 13 98 theme replacing 1916:1924 arg1 SBM 1926:1928 replacing SBM 1916:1928 replacing SBM with F-CSM or F-RSM in the diet of Hu sheep 1916:1972 Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism. 37007511 2 99 theme similar 441:447 arg1 origins 449:455 similar origins 441:455 similar origins 441:455 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 14 100 dep richness 2100:2107 arg1 the 2096:2098 the 2096:2098 the 2096:2098 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 6 101 theme protein 1096:1102 arg1 yield 1104:1108 the microbial crude protein yield 1076:1108 the microbial crude protein yield 1076:1108 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 6 101 theme protein 1096:1102 arg1 higher 1128:1133 higher 1128:1133 higher 1128:1133 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 6 102 theme microbial 1080:1088 arg1 yield 1104:1108 the microbial crude protein yield 1076:1108 the microbial crude protein yield 1076:1108 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 6 102 theme microbial 1080:1088 arg1 higher 1128:1133 higher 1128:1133 higher 1128:1133 In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). 37007511 3 103 dep differed 706:713 arg1 p < 0.05 730:737 p < 0.05 730:737 p < 0.05 730:737 Results The three groups' intake of dry matter differed significantly (p < 0.05). 37007511 9 104 theme CK 1479:1480 arg1 p < 0.05 1489:1496 p < 0.05 1489:1496 p < 0.05 1489:1496 In comparison to the other groups, Firmicutes were less abundant in the CK group (p < 0.05). 37007511 9 104 theme CK 1479:1480 arg1 group 1482:1486 the CK group 1475:1486 the CK group (p < 0.05) 1475:1497 In comparison to the other groups, Firmicutes were less abundant in the CK group (p < 0.05). 37007511 14 105 from influence 2083:2091 arg1 diversity 2113:2121 diversity 2113:2121 diversity 2113:2121 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 14 105 from influence 2083:2091 arg1 richness 2100:2107 richness 2100:2107 richness 2100:2107 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 14 106 dep Conclusion 2022:2031 arg1 has 2076:2078 has 2076:2078 has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels 2076:2170 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 0 107 theme cottonseed 10:19 arg1 meals 34:38 Fermented cottonseed and rapeseed meals 0:38 Fermented cottonseed and rapeseed meals 0:38 Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep. 37007511 2 108 theme starting 396:403 arg1 weights 410:416 starting body weights 396:416 starting body weights of 22.51 ± 2.84 kg and similar origins 396:455 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 0 109 theme rapeseed 25:32 arg1 meals 34:38 Fermented cottonseed and rapeseed meals 0:38 Fermented cottonseed and rapeseed meals 0:38 Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep. 37007511 13 110 theme Gene 1877:1880 arg1 prediction 1891:1900 Gene function prediction 1877:1900 Gene function prediction 1877:1900 Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism. 37007511 10 111 theme relative 1535:1542 arg1 abundance 1544:1552 a higher relative abundance 1526:1552 a higher relative abundance in the F-CSM and F-RSM groups 1526:1582 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 2 112 theme male 377:380 arg1 sheep 385:389 51 four-month-old indigenous male Hu sheep 348:389 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins 348:455 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 113 dep treatments 489:498 arg1 TMR 539:541 TMR 539:541 TMR 539:541 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 113 dep treatments 489:498 arg1 ration 531:536 total mixed ration 519:536 three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group) 483:656 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 7 114 theme activity 1267:1274 arg1 p < 0.05 1277:1284 p < 0.05 1277:1284 p < 0.05 1277:1284 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 114 theme activity 1267:1274 arg1 pepsin 1239:1244 pepsin 1239:1244 pepsin 1239:1244 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 114 theme activity 1267:1274 arg1 group 1230:1234 the F-RSM group 1220:1234 the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05) 1220:1285 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 114 theme activity 1267:1274 arg1 activity 1267:1274 cellulose enzyme activity 1250:1274 cellulose enzyme activity (p < 0.05) 1250:1285 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 2 115 theme 22.51 ± 2.84 kg 421:435 arg1 weights 410:416 starting body weights 396:416 starting body weights of 22.51 ± 2.84 kg and similar origins 396:455 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 8 116 theme relative 1292:1299 arg1 greater 1332:1338 greater 1332:1338 greater 1332:1338 The relative abundance of Bacteroidetes was greater in the CK and F-RSM groups compared to the F-CSM group (p < 0.05). 37007511 8 116 theme relative 1292:1299 arg1 abundance 1301:1309 The relative abundance 1288:1309 The relative abundance of Bacteroidetes 1288:1326 The relative abundance of Bacteroidetes was greater in the CK and F-RSM groups compared to the F-CSM group (p < 0.05). 37007511 2 117 contain containing 629:638 arg1 TMR 625:627 (3) fermented TMR 611:627 (3) fermented TMR containing RSM (F-RSM group) 611:656 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 117 contain containing 629:638 arg2 group 651:655 F-RSM group 645:655 F-RSM group 645:655 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 2 117 contain containing 629:638 arg2 RSM 640:642 RSM 640:642 RSM (F-RSM group) 640:656 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 12 118 theme acid 1834:1837 arg1 content 1839:1845 rumen butyric acid content 1820:1845 rumen butyric acid content 1820:1845 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 correlated with rumen butyric acid content and NH3-N content (p < 0.05). 37007511 2 119 theme four-month-old 351:364 arg1 sheep 385:389 51 four-month-old indigenous male Hu sheep 348:389 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins 348:455 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). 37007511 7 120 theme cellulose 1250:1258 arg1 p < 0.05 1277:1284 p < 0.05 1277:1284 p < 0.05 1277:1284 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 120 theme cellulose 1250:1258 arg1 activity 1267:1274 cellulose enzyme activity 1250:1274 cellulose enzyme activity (p < 0.05) 1250:1285 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 10 121 theme F-CSM 1561:1565 arg1 groups 1577:1582 the F-CSM and F-RSM groups 1557:1582 groups 1577:1582 Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). 37007511 15 122 theme VFA 2213:2215 arg1 yield 2217:2221 VFA yield 2213:2221 VFA yield 2213:2221 Replacement of SBM with F-CSM increased VFA yield and further promoted the performance of Hu sheep. 37007511 7 123 theme pepsin 1239:1244 arg1 p < 0.05 1277:1284 p < 0.05 1277:1284 p < 0.05 1277:1284 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 123 theme pepsin 1239:1244 arg1 pepsin 1239:1244 pepsin 1239:1244 pepsin 1239:1244 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 123 theme pepsin 1239:1244 arg1 group 1230:1234 the F-RSM group 1220:1234 the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05) 1220:1285 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 7 123 theme pepsin 1239:1244 arg1 activity 1267:1274 cellulose enzyme activity 1250:1274 cellulose enzyme activity (p < 0.05) 1250:1285 The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). 37007511 13 124 theme glycan 1986:1991 arg1 biosynthesis 1993:2004 glycan biosynthesis 1986:2004 glycan biosynthesis 1986:2004 Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism. 37007511 14 125 theme F-RSM 2062:2066 arg1 replacement 2037:2047 The replacement 2033:2047 The replacement of F-CSM and F-RSM for SBM 2033:2074 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 5 126 theme fatty 997:1001 arg1 acids 1003:1007 volatile fatty acids 988:1007 volatile fatty acids 988:1007 The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. 37007511 14 127 theme bacteria 2132:2139 arg1 diversity 2113:2121 diversity 2113:2121 diversity 2113:2121 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 14 127 theme bacteria 2132:2139 arg1 richness 2100:2107 richness 2100:2107 richness 2100:2107 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 0 128 from composition 124:134 arg1 sheep 142:146 Hu sheep 139:146 Hu sheep 139:146 Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep. 37007511 12 129 theme rumen 1820:1824 arg1 acid 1834:1837 rumen butyric acid 1820:1837 rumen butyric acid content 1820:1845 The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 correlated with rumen butyric acid content and NH3-N content (p < 0.05). 37007511 14 130 theme F-CSM 2052:2056 arg1 replacement 2037:2047 The replacement 2033:2047 The replacement of F-CSM and F-RSM for SBM 2033:2074 Conclusion The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. 37007511 15 131 theme SBM 2188:2190 arg1 Replacement 2173:2183 Replacement 2173:2183 Replacement of SBM with F-CSM 2173:2201 Replacement of SBM with F-CSM increased VFA yield and further promoted the performance of Hu sheep. 35223953 9 0 theme potential 1974:1982 arg1 biomarkers 1984:1993 potential biomarkers 1974:1993 potential biomarkers that were strongly correlated with oxidative stress and metabolism genes 1974:2066 Correlation analysis between microbiome and animal indicators found that seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 were found as potential biomarkers that were strongly correlated with oxidative stress and metabolism genes. 35223953 9 0 theme potential 1974:1982 arg1 genera 1809:1814 seven genera 1803:1814 seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 1803:1958 Correlation analysis between microbiome and animal indicators found that seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 were found as potential biomarkers that were strongly correlated with oxidative stress and metabolism genes. 35223953 6 1 theme molecular 1015:1023 arg1 mechanism 1025:1033 molecular mechanism 1015:1033 molecular mechanism study 1015:1039 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 8 2 theme Ruminiclostridium_9 1681:1699 arg1 abundance 1618:1626 the relative abundance 1605:1626 the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9 1605:1699 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 3 3 theme high-fat 523:530 arg1 HFD 538:540 HFD 538:540 HFD 538:540 In this study, we performed omics and molecular verification in high-fat diet (HFD)-fed rat, aiming to reveal the mechanism and provide molecular evidence. 35223953 3 3 theme high-fat 523:530 arg1 diet 532:535 high-fat diet 523:535 high-fat diet (HFD) 523:541 In this study, we performed omics and molecular verification in high-fat diet (HFD)-fed rat, aiming to reveal the mechanism and provide molecular evidence. 35223953 1 4 theme significant 231:241 arg1 benefit 250:256 significant health benefit 231:256 significant health benefit 231:256 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 6 5 dep lipogenesis 1119:1129 arg1 Kcnn2 1162:1166 Kcnn2 1162:1166 Kcnn2 1162:1166 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 5 dep lipogenesis 1119:1129 arg1 SCD1 1144:1147 SCD1 1144:1147 SCD1 1144:1147 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 5 dep lipogenesis 1119:1129 arg1 CD36 1138:1141 CD36 1138:1141 CD36 1138:1141 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 5 dep lipogenesis 1119:1129 arg1 FABP 1132:1135 FABP 1132:1135 FABP 1132:1135 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 5 dep lipogenesis 1119:1129 arg1 Cyp4a1 1150:1155 Cyp4a1 1150:1155 Cyp4a1 1150:1155 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 6 theme gene 1085:1088 arg1 expressions 1090:1100 the gene expressions 1081:1100 the gene expressions of biomarkers 1081:1114 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 1 7 theme new 151:153 arg1 tea 136:138 Instant dark tea 123:138 Instant dark tea (IDT) 123:144 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 1 7 theme new 151:153 arg1 product 155:161 a new product 149:161 a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients 149:352 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 9 8 theme Correlation 1730:1740 arg1 analysis 1742:1749 Correlation analysis 1730:1749 Correlation analysis between microbiome and animal indicators 1730:1790 Correlation analysis between microbiome and animal indicators found that seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 were found as potential biomarkers that were strongly correlated with oxidative stress and metabolism genes. 35223953 8 9 theme p 1719:1719 arg1 HFD 1714:1716 HFD 1714:1716 HFD (p < 0.01) 1714:1727 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 8 9 theme p 1719:1719 arg1 < 1721:1721 p < 0.01 1719:1726 p < 0.01 1719:1726 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 8 10 theme relative 1502:1509 arg1 composition 1511:1521 the relative composition 1498:1521 the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group 1498:1589 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 9 11 theme metabolism 2051:2060 arg1 genes 2062:2066 metabolism genes 2051:2066 metabolism genes 2051:2066 Correlation analysis between microbiome and animal indicators found that seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 were found as potential biomarkers that were strongly correlated with oxidative stress and metabolism genes. 35223953 5 12 theme serum 919:923 arg1 HDL-C 925:929 serum HDL-C 919:929 serum HDL-C 919:929 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 8 13 theme bacterium 1537:1545 arg1 Akkermansia 1547:1557 beneficial bacterium Akkermansia 1526:1557 beneficial bacterium Akkermansia 1526:1557 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 5 14 theme body 840:843 arg1 weight 845:850 the body weight 836:850 the body weight 836:850 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 6 15 theme HIDT 1042:1045 arg1 feeding 1047:1053 HIDT feeding 1042:1053 HIDT feeding 1042:1053 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 1 16 theme Instant 123:129 arg1 tea 136:138 Instant dark tea 123:138 Instant dark tea (IDT) 123:144 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 1 16 theme Instant 123:129 arg1 product 155:161 a new product 149:161 a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients 149:352 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 1 16 theme Instant 123:129 arg1 IDT 141:143 IDT 141:143 IDT 141:143 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 0 17 from Evidence 85:92 arg1 Hyperlipidaemia 28:42 Hyperlipidaemia 28:42 Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond 28:120 Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond. 35223953 5 18 theme GSH-Px 970:975 arg1 levels 944:949 the levels 940:949 the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2 906:985 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 6 19 theme glucose 1199:1205 arg1 glycolysis 1207:1216 glucose glycolysis 1199:1216 glucose glycolysis (Gck and ENO2) 1199:1231 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 7 20 theme gut 1336:1338 arg1 species 1350:1356 the gut microbial species 1332:1356 the gut microbial species 1332:1356 Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. 35223953 11 21 theme primary 2272:2278 arg1 evidence 2290:2297 the primary molecular evidence 2268:2297 the primary molecular evidence for the molecular mechanism 2268:2325 Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia. 35223953 4 22 theme bioactive 649:657 arg1 polysaccharides 699:713 237.9 mg/g total polysaccharides 682:713 237.9 mg/g total polysaccharides 682:713 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 4 22 theme bioactive 649:657 arg1 components 659:668 the major bioactive components 639:668 the major bioactive components in IDT 639:675 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 4 23 theme 336.6 716:720 arg1 mg/g 722:725 mg/g 722:725 mg/g 722:725 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 5 24 theme SOD 960:962 arg1 levels 944:949 the levels 940:949 the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2 906:985 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 7 25 theme Firmicutes 1444:1453 arg1 abundance 1412:1420 the increase abundance 1399:1420 the increase abundance of Proteobacteria and Firmicutes induced by HFD 1399:1468 Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. 35223953 11 26 theme novel 2342:2346 arg1 insights 2348:2355 novel insights 2342:2355 novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia 2342:2422 Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia. 35223953 4 27 theme total 727:731 arg1 polyphenols 733:743 336.6 mg/g total polyphenols 716:743 336.6 mg/g total polyphenols 716:743 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 0 28 theme Redox 97:101 arg1 Balance 103:109 Redox Balance 97:109 Redox Balance 97:109 Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond. 35223953 1 29 theme functional 331:340 arg1 ingredients 342:352 functional ingredients 331:352 functional ingredients 331:352 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 7 30 theme Proteobacteria 1425:1438 arg1 abundance 1412:1420 the increase abundance 1399:1420 the increase abundance of Proteobacteria and Firmicutes induced by HFD 1399:1468 Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. 35223953 0 31 from Hyperlipidaemia 28:42 arg1 Rat 65:67 High-Fat Diet-Fed Rat 47:67 High-Fat Diet-Fed Rat 47:67 Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond. 35223953 4 32 theme mg/g 688:691 arg1 polysaccharides 699:713 237.9 mg/g total polysaccharides 682:713 237.9 mg/g total polysaccharides 682:713 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 4 32 theme mg/g 688:691 arg1 components 659:668 the major bioactive components 639:668 the major bioactive components in IDT 639:675 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 0 33 theme Instant 0:6 arg1 Tea 13:15 Instant Dark Tea 0:15 Instant Dark Tea 0:15 Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond. 35223953 1 34 theme health 243:248 arg1 benefit 250:256 significant health benefit 231:256 significant health benefit 231:256 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 8 35 theme bacterium 1643:1651 arg1 abundance 1618:1626 the relative abundance 1605:1626 the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9 1605:1699 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 6 36 contain had 1055:1057 arg2 impact 1071:1076 significant impact 1059:1076 significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) 1059:1231 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 36 contain had 1055:1057 arg1 feeding 1047:1053 HIDT feeding 1042:1053 HIDT feeding 1042:1053 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 4 37 from components 659:668 arg1 IDT 673:675 IDT 673:675 IDT 673:675 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 0 38 theme High-Fat 47:54 arg1 Rat 65:67 High-Fat Diet-Fed Rat 47:67 High-Fat Diet-Fed Rat 47:67 Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond. 35223953 11 39 theme molecular 2307:2315 arg1 mechanism 2317:2325 the molecular mechanism 2303:2325 the molecular mechanism 2303:2325 Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia. 35223953 7 40 theme microbiome 1264:1273 arg1 study 1275:1279 gut microbiome study 1260:1279 gut microbiome study 1260:1279 Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. 35223953 5 41 dep IDT 780:782 arg1 g/kg 795:798 0.27-0.54 g/kg 785:798 0.27-0.54 g/kg for 12 weeks 785:811 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 4 42 theme 46.9 750:753 arg1 mg/g 755:758 mg/g 755:758 mg/g 755:758 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 6 43 theme liver 1236:1240 arg1 tissue 1242:1247 liver tissue 1236:1247 liver tissue 1236:1247 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 11 44 theme IDT 2401:2403 arg1 effect 2391:2396 the regulatory effect 2376:2396 the regulatory effect of IDT on hyperlipidaemia 2376:2422 Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia. 35223953 6 45 theme lipid 1170:1174 arg1 PPARγ 1187:1191 PPARγ 1187:1191 PPARγ 1187:1191 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 45 theme lipid 1170:1174 arg1 oxidation 1176:1184 lipid oxidation 1170:1184 lipid oxidation (PPARγ) 1170:1192 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 11 46 from effect 2391:2396 arg1 hyperlipidaemia 2408:2422 hyperlipidaemia 2408:2422 hyperlipidaemia 2408:2422 Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia. 35223953 6 47 theme biomarkers 1105:1114 arg1 expressions 1090:1100 the gene expressions 1081:1100 the gene expressions of biomarkers 1081:1114 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 8 48 dep bacterium 1643:1651 arg1 Ruminococcaceae_UCG-005 1653:1675 Ruminococcaceae_UCG-005 1653:1675 Ruminococcaceae_UCG-005 1653:1675 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 3 49 theme molecular 497:505 arg1 verification 507:518 molecular verification 497:518 molecular verification 497:518 In this study, we performed omics and molecular verification in high-fat diet (HFD)-fed rat, aiming to reveal the mechanism and provide molecular evidence. 35223953 9 50 theme oxidative 2030:2038 arg1 stress 2040:2045 oxidative stress 2030:2045 oxidative stress 2030:2045 Correlation analysis between microbiome and animal indicators found that seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 were found as potential biomarkers that were strongly correlated with oxidative stress and metabolism genes. 35223953 1 51 theme increasing 171:180 arg1 attention 182:190 increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients 171:352 increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients 171:352 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 7 52 theme family 1365:1370 arg1 level 1372:1376 the family level 1361:1376 the family level 1361:1376 Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. 35223953 6 53 theme significant 1059:1069 arg1 impact 1071:1076 significant impact 1059:1076 significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) 1059:1231 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 5 54 theme liver 954:958 arg1 SOD 960:962 liver SOD 954:962 liver SOD 954:962 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 3 55 theme -fed 542:545 arg1 rat 547:549 high-fat diet (HFD)-fed rat 523:549 high-fat diet (HFD)-fed rat 523:549 In this study, we performed omics and molecular verification in high-fat diet (HFD)-fed rat, aiming to reveal the mechanism and provide molecular evidence. 35223953 5 56 theme Nrf2 982:985 arg1 levels 944:949 the levels 940:949 the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2 906:985 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 11 57 theme regulatory 2380:2389 arg1 effect 2391:2396 the regulatory effect 2376:2396 the regulatory effect of IDT on hyperlipidaemia 2376:2422 Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia. 35223953 9 58 theme animal 1774:1779 arg1 indicators 1781:1790 animal indicators 1774:1790 animal indicators 1774:1790 Correlation analysis between microbiome and animal indicators found that seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 were found as potential biomarkers that were strongly correlated with oxidative stress and metabolism genes. 35223953 5 59 theme HDL-C 925:929 arg1 level 910:914 the level 906:914 the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2 906:985 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 8 60 theme beneficial 1526:1535 arg1 Akkermansia 1547:1557 beneficial bacterium Akkermansia 1526:1557 beneficial bacterium Akkermansia 1526:1557 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 7 61 theme microbial 1340:1348 arg1 species 1350:1356 the gut microbial species 1332:1356 the gut microbial species 1332:1356 Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. 35223953 11 62 theme molecular 2280:2288 arg1 evidence 2290:2297 the primary molecular evidence 2268:2297 the primary molecular evidence for the molecular mechanism 2268:2325 Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia. 35223953 6 63 from impact 1071:1076 arg1 glycolysis 1207:1216 glucose glycolysis 1199:1216 glucose glycolysis (Gck and ENO2) 1199:1231 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 63 from impact 1071:1076 arg1 PPARγ 1187:1191 PPARγ 1187:1191 PPARγ 1187:1191 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 63 from impact 1071:1076 arg1 expressions 1090:1100 the gene expressions 1081:1100 the gene expressions of biomarkers 1081:1114 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 63 from impact 1071:1076 arg1 oxidation 1176:1184 lipid oxidation 1170:1184 lipid oxidation (PPARγ) 1170:1192 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 63 from impact 1071:1076 arg1 lipogenesis 1119:1129 lipogenesis 1119:1129 lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2) 1119:1167 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 8 64 theme Akkermansia 1547:1557 arg1 composition 1511:1521 the relative composition 1498:1521 the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group 1498:1589 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 1 65 theme dark 131:134 arg1 tea 136:138 Instant dark tea 123:138 Instant dark tea (IDT) 123:144 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 1 65 theme dark 131:134 arg1 product 155:161 a new product 149:161 a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients 149:352 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 1 65 theme dark 131:134 arg1 IDT 141:143 IDT 141:143 IDT 141:143 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 2 66 from effect 414:419 arg1 hyperlipidaemia 424:438 hyperlipidaemia 424:438 hyperlipidaemia 424:438 However, the molecular mechanism underlying its regulatory effect on hyperlipidaemia is rarely studied. 35223953 6 67 theme mechanism 1025:1033 arg1 study 1035:1039 molecular mechanism study 1015:1039 molecular mechanism study 1015:1039 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 0 68 theme Molecular 75:83 arg1 Evidence 85:92 Molecular Evidence 75:92 Molecular Evidence 75:92 Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond. 35223953 8 69 theme Rikenellaceae_RC9_gut_group 1563:1589 arg1 composition 1511:1521 the relative composition 1498:1521 the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group 1498:1589 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 4 70 theme major 643:647 arg1 polysaccharides 699:713 237.9 mg/g total polysaccharides 682:713 237.9 mg/g total polysaccharides 682:713 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 4 70 theme major 643:647 arg1 components 659:668 the major bioactive components 639:668 the major bioactive components in IDT 639:675 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 1 71 theme high 309:312 arg1 concentration 314:326 its high concentration 305:326 its high concentration of functional ingredients 305:352 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 8 72 theme relative 1609:1616 arg1 abundance 1618:1626 the relative abundance 1605:1626 the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9 1605:1699 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 5 73 theme blood 871:875 arg1 glucose 877:883 blood glucose 871:883 blood glucose 871:883 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 10 74 theme body 2141:2144 arg1 weight 2146:2151 body weight 2141:2151 body weight 2141:2151 For instance, Ruminococcaceae_UCG-005 was significantly correlated with body weight, TG, HDL-C, Nfr2, FABP3, SCD1, Cyp4a1, and Kcnn2. 35223953 4 75 theme mg/g 722:725 arg1 polyphenols 733:743 336.6 mg/g total polyphenols 716:743 336.6 mg/g total polyphenols 716:743 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 0 76 theme Dark 8:11 arg1 Tea 13:15 Instant Dark Tea 0:15 Instant Dark Tea 0:15 Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond. 35223953 1 77 theme ingredients 342:352 arg1 concentration 314:326 its high concentration 305:326 its high concentration of functional ingredients 305:352 Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. 35223953 11 78 theme above 2221:2225 arg1 data 2227:2230 the above data 2217:2230 the above data obtained in this study 2217:2253 Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia. 35223953 4 79 theme 237.9 682:686 arg1 mg/g 688:691 mg/g 688:691 mg/g 688:691 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 8 80 theme harmful 1635:1641 arg1 bacterium 1643:1651 the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9 1631:1699 bacterium 1643:1651 HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). 35223953 2 81 theme regulatory 403:412 arg1 effect 414:419 its regulatory effect 399:419 its regulatory effect on hyperlipidaemia 399:438 However, the molecular mechanism underlying its regulatory effect on hyperlipidaemia is rarely studied. 35223953 3 82 theme molecular 595:603 arg1 evidence 605:612 molecular evidence 595:612 molecular evidence 595:612 In this study, we performed omics and molecular verification in high-fat diet (HFD)-fed rat, aiming to reveal the mechanism and provide molecular evidence. 35223953 4 83 theme total 693:697 arg1 polysaccharides 699:713 237.9 mg/g total polysaccharides 682:713 237.9 mg/g total polysaccharides 682:713 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 4 83 theme total 693:697 arg1 components 659:668 the major bioactive components 639:668 the major bioactive components in IDT 639:675 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 7 84 theme increase 1403:1410 arg1 abundance 1412:1420 the increase abundance 1399:1420 the increase abundance of Proteobacteria and Firmicutes induced by HFD 1399:1468 Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. 35223953 4 85 theme mg/g 755:758 arg1 EGCG 760:763 46.9 mg/g EGCG 750:763 46.9 mg/g EGCG 750:763 The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. 35223953 2 86 theme molecular 368:376 arg1 mechanism 378:386 the molecular mechanism 364:386 the molecular mechanism underlying its regulatory effect on hyperlipidaemia 364:438 However, the molecular mechanism underlying its regulatory effect on hyperlipidaemia is rarely studied. 35223953 0 87 theme Diet-Fed 56:63 arg1 Rat 65:67 High-Fat Diet-Fed Rat 47:67 High-Fat Diet-Fed Rat 47:67 Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond. 35223953 6 88 dep glycolysis 1207:1216 arg1 ENO2 1227:1230 ENO2 1227:1230 ENO2 1227:1230 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 6 88 dep glycolysis 1207:1216 arg1 Gck 1219:1221 Gck 1219:1221 Gck 1219:1221 For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. 35223953 5 89 theme CAT 965:967 arg1 levels 944:949 the levels 940:949 the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2 906:985 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 5 90 theme HFD 1000:1002 arg1 group 1004:1008 HFD group 1000:1008 HFD group 1000:1008 Rats fed with IDT (0.27-0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. 35223953 7 91 theme gut 1260:1262 arg1 study 1275:1279 gut microbiome study 1260:1279 gut microbiome study 1260:1279 Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. 35223953 0 92 from Beyond 115:120 arg1 Hyperlipidaemia 28:42 Hyperlipidaemia 28:42 Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond 28:120 Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond. 36981182 0 0 theme Foaming 81:87 arg1 Property 89:96 a High Emulsifying and Foaming Property 58:96 a High Emulsifying and Foaming Property 58:96 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 36981182 7 1 theme fraction 1128:1135 arg1 solubility 1114:1123 The solubility 1110:1123 The solubility of fraction 2 and 4 1110:1143 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 10 2 theme meals 1833:1837 arg1 utilization 1809:1819 the high-value utilization 1794:1819 the high-value utilization of flaxseed meals 1794:1837 This study provides a reference to promote the high-value utilization of flaxseed meals. 36981182 1 3 theme new 154:156 arg1 focus 158:162 A new focus 152:162 A new focus with respect to the extraction of plant protein 152:210 A new focus with respect to the extraction of plant protein is that ingredient enrichment should target functionality instead of pursuing purity. 36981182 9 4 theme structure 1591:1599 arg1 formation 1570:1578 the formation 1566:1578 the formation of network structure 1566:1599 Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. 36981182 2 5 used used 349:352 arg2 method 338:343 the sequence aqueous extraction method 306:343 the sequence aqueous extraction method 306:343 Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. 36981182 3 6 theme recovery 522:529 arg1 rate 531:534 The total recovery rate 512:534 The total recovery rate of flaxseed protein obtained by the sequence extraction approach 512:599 The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. 36981182 3 6 theme recovery 522:529 arg1 % 617:617 more than 80% 605:617 more than 80% 605:617 The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. 36981182 6 7 theme protein 1030:1036 arg1 content 1038:1044 protein content 1030:1044 protein content of 73.05% 1030:1054 After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. 36981182 6 8 dep supernatant 997:1007 arg1 the 980:982 the 980:982 the 980:982 After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. 36981182 3 9 theme extraction 581:590 arg1 approach 592:599 the sequence extraction approach 568:599 the sequence extraction approach 568:599 The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. 36981182 8 10 theme sodium 1391:1396 arg1 caseinate 1398:1406 commercial sodium caseinate 1380:1406 commercial sodium caseinate 1380:1406 The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. 36981182 3 11 theme total 516:520 arg1 rate 531:534 The total recovery rate 512:534 The total recovery rate of flaxseed protein obtained by the sequence extraction approach 512:599 The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. 36981182 3 11 theme total 516:520 arg1 % 617:617 more than 80% 605:617 more than 80% 605:617 The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. 36981182 9 12 theme layers 1663:1668 arg1 formation 1617:1625 the formation 1613:1625 the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence 1613:1748 Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. 36981182 4 13 theme deionized 709:717 arg1 water 719:723 deionized water 709:723 deionized water to obtain fraction 1 (supernatant) 709:758 The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. 36981182 8 14 theme commercial 1380:1389 arg1 caseinate 1398:1406 commercial sodium caseinate 1380:1406 commercial sodium caseinate 1380:1406 The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. 36981182 3 15 theme flaxseed 539:546 arg1 protein 548:554 flaxseed protein 539:554 flaxseed protein obtained by the sequence extraction approach 539:599 The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. 36981182 9 16 from polysaccharides 1518:1532 arg1 fractions 1537:1545 fractions 1537:1545 fractions 1537:1545 Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. 36981182 3 17 theme protein 548:554 arg1 rate 531:534 The total recovery rate 512:534 The total recovery rate of flaxseed protein obtained by the sequence extraction approach 512:599 The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. 36981182 3 17 theme protein 548:554 arg1 % 617:617 more than 80% 605:617 more than 80% 605:617 The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. 36981182 9 18 theme emulsion 1691:1698 arg1 flocculation 1700:1711 emulsion flocculation 1691:1711 emulsion flocculation 1691:1711 Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. 36981182 8 19 theme emulsifying 1302:1312 arg1 properties 1314:1323 The emulsifying properties 1298:1323 The emulsifying properties of fractions 1, 2, and 5 1298:1348 The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. 36981182 8 19 theme emulsifying 1302:1312 arg1 greater 1359:1365 greater 1359:1365 greater 1359:1365 The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. 36981182 4 20 dep fraction 804:811 arg1 precipitate 836:846 precipitate 836:846 precipitate 836:846 The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. 36981182 4 20 dep fraction 804:811 arg1 supernatant 816:826 supernatant 816:826 supernatant 816:826 The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. 36981182 4 20 dep fraction 804:811 arg1 3 833:833 3 833:833 3 833:833 The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. 36981182 4 20 dep fraction 804:811 arg1 2 813:813 2 813:813 2 813:813 The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. 36981182 2 21 theme sequence 310:317 arg1 method 338:343 the sequence aqueous extraction method 306:343 the sequence aqueous extraction method 306:343 Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. 36981182 2 22 theme natural 395:401 arg1 fractions 403:411 five protein-polysaccharide natural fractions 367:411 five protein-polysaccharide natural fractions from flaxseed meal 367:430 Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. 36981182 9 23 theme smoother 1642:1649 arg1 layers 1663:1668 tighter and smoother interfacial layers 1630:1668 tighter and smoother interfacial layers 1630:1668 Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. 36981182 2 24 theme protein-polysaccharide 372:393 arg1 fractions 403:411 five protein-polysaccharide natural fractions 367:411 five protein-polysaccharide natural fractions from flaxseed meal 367:430 Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. 36981182 0 25 theme Protein 26:32 arg1 Co-Extraction 0:12 Co-Extraction 0:12 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 0:150 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 36981182 0 26 theme Sequence 122:129 arg1 Approach 142:149 the Sequence Extraction Approach 118:149 the Sequence Extraction Approach 118:149 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 36981182 9 27 theme Cryo-SEM 1489:1496 arg1 results 1498:1504 Cryo-SEM results 1489:1504 Cryo-SEM results 1489:1504 Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. 36981182 5 28 theme fraction 897:904 arg1 Part 885:888 Part 885:888 Part of the fraction 2 885:906 Part of the fraction 2 was taken out, followed by adjusting its pH to 4.2. 36981182 0 29 theme Flaxseed 17:24 arg1 Protein 26:32 Flaxseed Protein 17:32 Flaxseed Protein 17:32 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 36981182 4 30 theme alkali 862:867 arg1 solubilization 869:882 weak alkali solubilization 857:882 weak alkali solubilization 857:882 The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. 36981182 6 31 with supernatant 997:1007 arg1 content 1038:1044 protein content 1030:1044 protein content of 73.05% 1030:1054 After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. 36981182 3 32 theme sequence 572:579 arg1 approach 592:599 the sequence extraction approach 568:599 the sequence extraction approach 568:599 The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. 36981182 7 33 theme fraction 1200:1207 arg1 times 1222:1226 12.76 times 1216:1226 12.76 times 1216:1226 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 7 33 theme fraction 1200:1207 arg1 stability 1187:1195 stability 1187:1195 stability of fraction 5 1187:1209 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 7 33 theme fraction 1200:1207 arg1 ability 1175:1181 the foaming ability 1163:1181 the foaming ability 1163:1181 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 0 34 theme Polysaccharide 38:51 arg1 Co-Extraction 0:12 Co-Extraction 0:12 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 0:150 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 36981182 7 35 theme flaxseed 1266:1273 arg1 protein 1275:1281 commercial flaxseed protein 1255:1281 commercial flaxseed protein 1255:1281 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 6 36 theme albumin-rich 984:995 arg1 supernatant 997:1007 albumin-rich supernatant 984:1007 albumin-rich supernatant 984:1007 After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. 36981182 6 36 theme albumin-rich 984:995 arg1 fraction 1083:1090 fraction 4 1083:1092 fraction 4 1083:1092 After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. 36981182 6 36 theme albumin-rich 984:995 arg1 fraction 1098:1105 fraction 5 1098:1107 fraction 5 1098:1107 After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. 36981182 1 37 theme plant 198:202 arg1 protein 204:210 plant protein 198:210 plant protein 198:210 A new focus with respect to the extraction of plant protein is that ingredient enrichment should target functionality instead of pursuing purity. 36981182 2 38 theme functional 471:480 arg1 properties 482:491 functional properties 471:491 functional properties 471:491 Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. 36981182 0 39 theme Extraction 131:140 arg1 Approach 142:149 the Sequence Extraction Approach 118:149 the Sequence Extraction Approach 118:149 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 36981182 6 40 with precipitate 1013:1023 arg1 content 1038:1044 protein content 1030:1044 protein content of 73.05% 1030:1054 After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. 36981182 1 41 theme protein 204:210 arg1 extraction 184:193 the extraction 180:193 the extraction of plant protein 180:210 A new focus with respect to the extraction of plant protein is that ingredient enrichment should target functionality instead of pursuing purity. 36981182 8 42 theme high-efficiency 1460:1474 arg1 fractions 1429:1437 these fractions 1423:1437 these fractions 1423:1437 The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. 36981182 8 42 theme high-efficiency 1460:1474 arg1 emulsifiers 1476:1486 high-efficiency emulsifiers 1460:1486 high-efficiency emulsifiers 1460:1486 The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. 36981182 7 43 theme 4 1143:1143 arg1 solubility 1114:1123 The solubility 1110:1123 The solubility of fraction 2 and 4 1110:1143 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 7 44 theme foaming 1167:1173 arg1 times 1222:1226 12.76 times 1216:1226 12.76 times 1216:1226 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 7 44 theme foaming 1167:1173 arg1 ability 1175:1181 the foaming ability 1163:1181 the foaming ability 1163:1181 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 10 45 theme high-value 1798:1807 arg1 utilization 1809:1819 the high-value utilization 1794:1819 the high-value utilization of flaxseed meals 1794:1837 This study provides a reference to promote the high-value utilization of flaxseed meals. 36981182 9 46 theme network 1583:1589 arg1 structure 1591:1599 network structure 1583:1599 network structure 1583:1599 Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. 36981182 8 47 used utilized 1448:1455 arg2 fractions 1429:1437 these fractions 1423:1437 these fractions 1423:1437 The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. 36981182 8 47 used utilized 1448:1455 arg2 emulsifiers 1476:1486 high-efficiency emulsifiers 1460:1486 high-efficiency emulsifiers 1460:1486 The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. 36981182 7 48 theme commercial 1255:1264 arg1 protein 1275:1281 commercial flaxseed protein 1255:1281 commercial flaxseed protein 1255:1281 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 4 49 theme weak 857:860 arg1 solubilization 869:882 weak alkali solubilization 857:882 weak alkali solubilization 857:882 The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. 36981182 0 50 with Co-Extraction 0:12 arg1 Property 89:96 a High Emulsifying and Foaming Property 58:96 a High Emulsifying and Foaming Property 58:96 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 36981182 2 51 theme extraction 327:336 arg1 method 338:343 the sequence aqueous extraction method 306:343 the sequence aqueous extraction method 306:343 Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. 36981182 9 52 theme interfacial 1651:1661 arg1 layers 1663:1668 tighter and smoother interfacial layers 1630:1668 tighter and smoother interfacial layers 1630:1668 Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. 36981182 9 53 theme tighter 1630:1636 arg1 layers 1663:1668 tighter and smoother interfacial layers 1630:1668 tighter and smoother interfacial layers 1630:1668 Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. 36981182 3 54 theme existing 650:657 arg1 reports 659:665 the existing reports 646:665 the existing reports 646:665 The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. 36981182 7 55 theme higher 1243:1248 arg1 ability 1175:1181 the foaming ability 1163:1181 the foaming ability 1163:1181 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 7 55 theme higher 1243:1248 arg1 times 1222:1226 12.76 times 1216:1226 12.76 times 1216:1226 The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. 36981182 2 56 from meal 427:430 arg1 fractions 403:411 five protein-polysaccharide natural fractions 367:411 five protein-polysaccharide natural fractions from flaxseed meal 367:430 Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. 36981182 2 57 theme aqueous 319:325 arg1 method 338:343 the sequence aqueous extraction method 306:343 the sequence aqueous extraction method 306:343 Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. 36981182 6 58 theme % 1054:1054 arg1 content 1038:1044 protein content 1030:1044 protein content of 73.05% 1030:1054 After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. 36981182 0 59 theme Emulsifying 65:75 arg1 Property 89:96 a High Emulsifying and Foaming Property 58:96 a High Emulsifying and Foaming Property 58:96 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 36981182 2 60 theme flaxseed 418:425 arg1 meal 427:430 flaxseed meal 418:430 flaxseed meal 418:430 Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. 36981182 8 61 theme fractions 1328:1336 arg1 properties 1314:1323 The emulsifying properties 1298:1323 The emulsifying properties of fractions 1, 2, and 5 1298:1348 The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. 36981182 8 61 theme fractions 1328:1336 arg1 greater 1359:1365 greater 1359:1365 greater 1359:1365 The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. 36981182 4 62 theme flaxseed 681:688 arg1 meal 690:693 The defatted flaxseed meal 668:693 The defatted flaxseed meal 668:693 The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. 36981182 1 63 theme ingredient 220:229 arg1 enrichment 231:240 ingredient enrichment 220:240 ingredient enrichment 220:240 A new focus with respect to the extraction of plant protein is that ingredient enrichment should target functionality instead of pursuing purity. 36981182 0 64 theme High 60:63 arg1 Property 89:96 a High Emulsifying and Foaming Property 58:96 a High Emulsifying and Foaming Property 58:96 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 36981182 10 65 theme flaxseed 1824:1831 arg1 meals 1833:1837 flaxseed meals 1824:1837 flaxseed meals 1824:1837 This study provides a reference to promote the high-value utilization of flaxseed meals. 36981182 0 66 dep Co-Extraction 0:12 arg1 Enrichment 99:108 Enrichment 99:108 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 0:150 Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach. 36981182 4 67 theme defatted 672:679 arg1 meal 690:693 The defatted flaxseed meal 668:693 The defatted flaxseed meal 668:693 The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. 36461233 0 0 theme coat 75:78 arg1 fiber 88:92 mung bean coat dietary fiber 65:92 mung bean coat dietary fiber 65:92 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 6 1 theme functional 1346:1355 arg1 foods 1357:1361 functional foods 1346:1361 functional foods 1346:1361 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 6 2 theme products 1505:1512 arg1 value 1488:1492 the added value 1478:1492 the added value of related products 1478:1512 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 5 3 theme reactive 1018:1025 arg1 ROS 1043:1045 ROS 1043:1045 ROS 1043:1045 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 3 theme reactive 1018:1025 arg1 species 1034:1040 reactive oxygen species 1018:1040 reactive oxygen species (ROS) 1018:1046 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 0 4 theme bean 70:73 arg1 fiber 88:92 mung bean coat dietary fiber 65:92 mung bean coat dietary fiber 65:92 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 1 5 theme subsequent 319:328 arg1 separation 330:339 subsequent separation 319:339 subsequent separation 319:339 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 5 6 theme oxygen 1027:1032 arg1 ROS 1043:1045 ROS 1043:1045 ROS 1043:1045 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 6 theme oxygen 1027:1032 arg1 species 1034:1040 reactive oxygen species 1018:1040 reactive oxygen species (ROS) 1018:1046 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 7 theme antioxidant 883:893 arg1 assays 904:909 The antioxidant activity assays 879:909 The antioxidant activity assays 879:909 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 8 from effects 962:968 arg1 ROS 1043:1045 ROS 1043:1045 ROS 1043:1045 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 8 from effects 962:968 arg1 ABTS+• 980:985 ABTS+• 980:985 ABTS+• 980:985 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 8 from effects 962:968 arg1 species 1034:1040 reactive oxygen species 1018:1040 reactive oxygen species (ROS) 1018:1046 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 8 from effects 962:968 arg1 elegans 1066:1072 Caenorhabditis elegans 1051:1072 Caenorhabditis elegans (C. elegans) 1051:1085 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 8 from effects 962:968 arg1 radicals 997:1004 DPPH•, ABTS+•, •OH free radicals 973:1004 radicals 997:1004 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 3 9 theme 615.88 μg/g 661:671 arg1 DW 673:674 615.88 μg/g DW 661:674 615.88 μg/g DW 661:674 The purification enriched flavonoids, with high contents of catechin (1419.03 μg/g DW) and vitexin (615.88 μg/g DW). 36461233 3 9 theme 615.88 μg/g 661:671 arg1 vitexin 652:658 vitexin 652:658 vitexin (615.88 μg/g DW) 652:675 The purification enriched flavonoids, with high contents of catechin (1419.03 μg/g DW) and vitexin (615.88 μg/g DW). 36461233 4 10 theme crude 863:867 arg1 extracts 869:876 the reported crude extracts 850:876 the reported crude extracts 850:876 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 4 11 theme significant 728:738 arg1 activity 762:769 significant reversible inhibitory activity 728:769 significant reversible inhibitory activity against α-glucosidase 728:791 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 0 12 theme dietary 80:86 arg1 fiber 88:92 mung bean coat dietary fiber 65:92 mung bean coat dietary fiber 65:92 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 4 13 theme reported 854:861 arg1 extracts 869:876 the reported crude extracts 850:876 the reported crude extracts 850:876 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 6 14 theme coat 1324:1327 arg1 fiber 1337:1341 mung bean coat dietary fiber 1314:1341 mung bean coat dietary fiber 1314:1341 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 6 15 theme dietary 1366:1372 arg1 supplements 1374:1384 dietary supplements 1366:1384 dietary supplements 1366:1384 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 6 16 theme mung 1438:1441 arg1 bean 1443:1446 mung bean 1438:1446 mung bean coat resources 1438:1461 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 4 17 theme inhibitory 751:760 arg1 activity 762:769 significant reversible inhibitory activity 728:769 significant reversible inhibitory activity against α-glucosidase 728:791 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 6 18 theme resources 1453:1461 arg1 utilization 1423:1433 the scientific utilization 1408:1433 the scientific utilization of mung bean coat resources 1408:1461 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 2 19 theme purified 382:389 arg1 products 391:398 the purified products 378:398 the purified products 378:398 The composition of the purified products was identified and quantified, 44 major compounds were detected, with the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW. 36461233 6 20 theme bean 1319:1322 arg1 fiber 1337:1341 mung bean coat dietary fiber 1314:1341 mung bean coat dietary fiber 1314:1341 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 6 21 from fiber 1337:1341 arg1 applications 1275:1286 the applications 1271:1286 the applications of bound polyphenols from mung bean coat dietary fiber 1271:1341 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 6 21 from fiber 1337:1341 arg1 polyphenols 1297:1307 bound polyphenols 1291:1307 bound polyphenols from mung bean coat dietary fiber 1291:1341 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 4 22 theme reversible 740:749 arg1 activity 762:769 significant reversible inhibitory activity 728:769 significant reversible inhibitory activity against α-glucosidase 728:791 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 2 23 contain contained 528:536 arg2 DW 557:558 up to 8881.90 μg/g DW 538:558 up to 8881.90 μg/g DW 538:558 The composition of the purified products was identified and quantified, 44 major compounds were detected, with the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW. 36461233 2 23 contain contained 528:536 arg1 acid 516:519 p-hydroxybenzoic acid 499:519 p-hydroxybenzoic acid 499:519 The composition of the purified products was identified and quantified, 44 major compounds were detected, with the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW. 36461233 1 24 theme macroporous 164:174 arg1 resins 176:181 seven macroporous resins 158:181 seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) 158:247 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 2 25 theme major 434:438 arg1 compounds 440:448 44 major compounds 431:448 44 major compounds 431:448 The composition of the purified products was identified and quantified, 44 major compounds were detected, with the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW. 36461233 6 26 from sights 1259:1264 arg1 foods 1357:1361 functional foods 1346:1361 functional foods 1346:1361 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 6 26 from sights 1259:1264 arg1 supplements 1374:1384 dietary supplements 1366:1384 dietary supplements 1366:1384 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 2 27 theme phenolic 479:486 arg1 acid 488:491 the main phenolic acid 470:491 the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW 470:558 The composition of the purified products was identified and quantified, 44 major compounds were detected, with the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW. 36461233 6 28 theme NKA-9 1120:1124 arg1 resin 1138:1142 NKA-9 macroporous resin 1120:1142 NKA-9 macroporous resin 1120:1142 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 6 29 theme related 1497:1503 arg1 products 1505:1512 related products 1497:1512 related products 1497:1512 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 1 30 theme resins 176:181 arg1 performance 143:153 the static adsorption-desorption performance 110:153 the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) 110:247 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 6 31 theme new 1255:1257 arg1 sights 1259:1264 new sights 1255:1264 new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements 1255:1384 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 6 32 theme MBDF-BP 1169:1175 arg1 extracts 1177:1184 MBDF-BP extracts 1169:1184 MBDF-BP extracts 1169:1184 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 6 33 theme mung 1314:1317 arg1 fiber 1337:1341 mung bean coat dietary fiber 1314:1341 mung bean coat dietary fiber 1314:1341 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 5 34 theme distinct 942:949 arg1 effects 962:968 distinct scavenging effects 942:968 distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans) 942:1085 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 4 35 theme mixed-type 798:807 arg1 superior 838:845 superior 838:845 superior 838:845 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 4 35 theme mixed-type 798:807 arg1 manner 820:825 a mixed-type inhibition manner 796:825 a mixed-type inhibition manner 796:825 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 1 36 theme bound 187:191 arg1 polyphenols 193:203 bound polyphenols 187:203 bound polyphenols from mung bean coat dietary fiber (MBDF-BP) 187:247 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 6 37 theme scientific 1412:1421 arg1 utilization 1423:1433 the scientific utilization 1408:1433 the scientific utilization of mung bean coat resources 1408:1461 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 5 38 theme DPPH• 973:977 arg1 ABTS+• 980:985 ABTS+• 980:985 ABTS+• 980:985 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 38 theme DPPH• 973:977 arg1 radicals 997:1004 DPPH•, ABTS+•, •OH free radicals 973:1004 radicals 997:1004 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 39 theme scavenging 951:960 arg1 effects 962:968 distinct scavenging effects 942:968 distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans) 942:1085 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 6 40 theme added 1482:1486 arg1 value 1488:1492 the added value 1478:1492 the added value of related products 1478:1512 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 1 41 theme NKA-9 267:271 arg1 resin 285:289 NKA-9 macroporous resin 267:289 NKA-9 macroporous resin 267:289 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 6 42 theme polyphenols 1297:1307 arg1 applications 1275:1286 the applications 1271:1286 the applications of bound polyphenols from mung bean coat dietary fiber 1271:1341 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 3 43 theme 1419.03 μg/g 631:642 arg1 catechin 621:628 catechin 621:628 catechin (1419.03 μg/g DW) 621:646 The purification enriched flavonoids, with high contents of catechin (1419.03 μg/g DW) and vitexin (615.88 μg/g DW). 36461233 3 43 theme 1419.03 μg/g 631:642 arg1 DW 644:645 1419.03 μg/g DW 631:645 1419.03 μg/g DW 631:645 The purification enriched flavonoids, with high contents of catechin (1419.03 μg/g DW) and vitexin (615.88 μg/g DW). 36461233 2 44 dep 8881.90 μg/g 544:555 arg1 to 541:542 to 541:542 to 541:542 The composition of the purified products was identified and quantified, 44 major compounds were detected, with the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW. 36461233 1 45 theme macroporous 273:283 arg1 resin 285:289 NKA-9 macroporous resin 267:289 NKA-9 macroporous resin 267:289 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 6 46 theme bound 1291:1295 arg1 polyphenols 1297:1307 bound polyphenols 1291:1307 bound polyphenols from mung bean coat dietary fiber 1291:1341 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 6 47 theme antioxidant 1202:1212 arg1 activity 1214:1221 its antioxidant activity 1198:1221 its antioxidant activity 1198:1221 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 2 48 theme products 391:398 arg1 composition 363:373 The composition 359:373 The composition of the purified products 359:398 The composition of the purified products was identified and quantified, 44 major compounds were detected, with the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW. 36461233 0 49 theme polyphenols 48:58 arg1 composition 14:24 composition 14:24 composition 14:24 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 0 49 theme polyphenols 48:58 arg1 Purification 0:11 Purification 0:11 Purification 0:11 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 0 49 theme polyphenols 48:58 arg1 activity 30:37 activity 30:37 activity 30:37 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 3 50 theme catechin 621:628 arg1 contents 609:616 high contents 604:616 high contents of catechin (1419.03 μg/g DW) and vitexin (615.88 μg/g DW) 604:675 The purification enriched flavonoids, with high contents of catechin (1419.03 μg/g DW) and vitexin (615.88 μg/g DW). 36461233 6 51 from applications 1275:1286 arg1 fiber 1337:1341 mung bean coat dietary fiber 1314:1341 mung bean coat dietary fiber 1314:1341 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 5 52 theme activity 895:902 arg1 assays 904:909 The antioxidant activity assays 879:909 The antioxidant activity assays 879:909 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 0 53 theme bound 42:46 arg1 polyphenols 48:58 bound polyphenols 42:58 bound polyphenols 42:58 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 1 54 from fiber 233:237 arg1 polyphenols 193:203 bound polyphenols 187:203 bound polyphenols from mung bean coat dietary fiber (MBDF-BP) 187:247 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 4 55 theme inhibition 809:818 arg1 superior 838:845 superior 838:845 superior 838:845 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 4 55 theme inhibition 809:818 arg1 manner 820:825 a mixed-type inhibition manner 796:825 a mixed-type inhibition manner 796:825 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 5 56 dep elegans 1066:1072 arg1 elegans 1078:1084 C. elegans 1075:1084 C. elegans 1075:1084 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 3 57 theme vitexin 652:658 arg1 contents 609:616 high contents 604:616 high contents of catechin (1419.03 μg/g DW) and vitexin (615.88 μg/g DW) 604:675 The purification enriched flavonoids, with high contents of catechin (1419.03 μg/g DW) and vitexin (615.88 μg/g DW). 36461233 3 58 theme high 604:607 arg1 contents 609:616 high contents 604:616 high contents of catechin (1419.03 μg/g DW) and vitexin (615.88 μg/g DW) 604:675 The purification enriched flavonoids, with high contents of catechin (1419.03 μg/g DW) and vitexin (615.88 μg/g DW). 36461233 4 59 theme purified 690:697 arg1 pMBDF-BP 709:716 pMBDF-BP 709:716 pMBDF-BP 709:716 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 4 59 theme purified 690:697 arg1 products 699:706 The MBDF-BP purified products 678:706 The MBDF-BP purified products (pMBDF-BP) 678:717 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 1 60 theme bean 215:218 arg1 MBDF-BP 240:246 MBDF-BP 240:246 MBDF-BP 240:246 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 1 60 theme bean 215:218 arg1 fiber 233:237 mung bean coat dietary fiber 210:237 mung bean coat dietary fiber (MBDF-BP) 210:247 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 6 61 theme macroporous 1126:1136 arg1 resin 1138:1142 NKA-9 macroporous resin 1120:1142 NKA-9 macroporous resin 1120:1142 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 0 62 from fiber 88:92 arg1 composition 14:24 composition 14:24 composition 14:24 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 0 62 from fiber 88:92 arg1 Purification 0:11 Purification 0:11 Purification 0:11 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 0 62 from fiber 88:92 arg1 activity 30:37 activity 30:37 activity 30:37 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 4 63 theme MBDF-BP 682:688 arg1 pMBDF-BP 709:716 pMBDF-BP 709:716 pMBDF-BP 709:716 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 4 63 theme MBDF-BP 682:688 arg1 products 699:706 The MBDF-BP purified products 678:706 The MBDF-BP purified products (pMBDF-BP) 678:717 The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. 36461233 6 64 theme dietary 1329:1335 arg1 fiber 1337:1341 mung bean coat dietary fiber 1314:1341 mung bean coat dietary fiber 1314:1341 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 1 65 theme coat 220:223 arg1 MBDF-BP 240:246 MBDF-BP 240:246 MBDF-BP 240:246 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 1 65 theme coat 220:223 arg1 fiber 233:237 mung bean coat dietary fiber 210:237 mung bean coat dietary fiber (MBDF-BP) 210:247 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 0 66 theme mung 65:68 arg1 fiber 88:92 mung bean coat dietary fiber 65:92 mung bean coat dietary fiber 65:92 Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber. 36461233 1 67 theme mung 210:213 arg1 bean 215:218 mung bean 210:218 mung bean coat dietary fiber (MBDF-BP) 210:247 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 5 68 theme •OH 988:990 arg1 ABTS+• 980:985 ABTS+• 980:985 ABTS+• 980:985 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 68 theme •OH 988:990 arg1 radicals 997:1004 DPPH•, ABTS+•, •OH free radicals 973:1004 radicals 997:1004 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 1 69 theme static 114:119 arg1 performance 143:153 the static adsorption-desorption performance 110:153 the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) 110:247 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 6 70 theme coat 1448:1451 arg1 resources 1453:1461 mung bean coat resources 1438:1461 mung bean coat resources 1438:1461 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 1 71 theme dietary 225:231 arg1 MBDF-BP 240:246 MBDF-BP 240:246 MBDF-BP 240:246 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 1 71 theme dietary 225:231 arg1 fiber 233:237 mung bean coat dietary fiber 210:237 mung bean coat dietary fiber (MBDF-BP) 210:247 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 2 72 theme main 474:477 arg1 acid 488:491 the main phenolic acid 470:491 the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW 470:558 The composition of the purified products was identified and quantified, 44 major compounds were detected, with the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW. 36461233 5 73 theme free 992:995 arg1 ABTS+• 980:985 ABTS+• 980:985 ABTS+• 980:985 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 5 73 theme free 992:995 arg1 radicals 997:1004 DPPH•, ABTS+•, •OH free radicals 973:1004 radicals 997:1004 The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). 36461233 1 74 theme adsorption-desorption 121:141 arg1 performance 143:153 the static adsorption-desorption performance 110:153 the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) 110:247 In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. 36461233 6 75 theme bean 1443:1446 arg1 resources 1453:1461 mung bean coat resources 1438:1461 mung bean coat resources 1438:1461 These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products. 36461233 2 76 theme p-hydroxybenzoic 499:514 arg1 acid 516:519 p-hydroxybenzoic acid 499:519 p-hydroxybenzoic acid 499:519 The composition of the purified products was identified and quantified, 44 major compounds were detected, with the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 μg/g DW. 35548566 4 0 dep obesity 512:518 arg1 microbiota 528:537 microbiota 528:537 microbiota 528:537 In the present study, we prepared the MOP and evaluated its effects on obesity and gut microbiota in high-fat diet (HFD)-induced C57BL/6J mice. 35548566 7 1 theme lipid 1025:1029 arg1 accumulation 1031:1042 lipid accumulation 1025:1042 lipid accumulation 1025:1042 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 8 2 theme Bacteroides 1374:1384 arg1 abundance 1361:1369 the abundance 1357:1369 the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter 1357:1429 In addition, MOP positively reshaped the gut microbiota composition, significantly increasing the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter, while decreasing the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity. 35548566 7 3 theme pro-inflammatory 1143:1158 arg1 cytokines 1160:1168 pro-inflammatory cytokines 1143:1168 pro-inflammatory cytokines 1143:1168 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 5 4 theme chow 639:642 arg1 diet 644:647 a normal chow diet 630:647 a normal chow diet (NCD group) 630:659 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 5 4 theme chow 639:642 arg1 group 654:658 NCD group 650:658 NCD group 650:658 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 10 5 dep potential 1785:1793 arg1 prevent 1805:1811 prevent 1805:1811 to prevent obesity 1802:1819 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 10 5 dep potential 1785:1793 arg1 modulating 1825:1834 modulating 1825:1834 modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic 1825:1911 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 3 6 theme biological 313:322 arg1 activities 324:333 the biological activities 309:333 the biological activities of M. oleifera polysaccharides (MOP) in regulating gut microbiota and alleviating obesity 309:423 However, the biological activities of M. oleifera polysaccharides (MOP) in regulating gut microbiota and alleviating obesity remain obscure. 35548566 9 7 theme MOP 1586:1588 arg1 supplementation 1590:1604 MOP supplementation 1586:1604 MOP supplementation 1586:1604 These results demonstrated that MOP supplementation has a protective effect against HFD-induced obesity in mice, which was associated with reshaping the gut microbiota. 35548566 7 8 theme cytokines 1160:1168 arg1 secretion 1130:1138 the secretion 1126:1138 the secretion of pro-inflammatory cytokines 1126:1168 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 6 9 theme microbiota 874:883 arg1 composition 885:895 gut microbiota composition 870:895 gut microbiota composition 870:895 Physiological, histological, biochemical parameters, genes related to lipid metabolism, and gut microbiota composition were compared among five experimental groups. 35548566 0 10 theme Gut 108:110 arg1 Microbiota 112:121 Modulating Gut Microbiota 97:121 Modulating Gut Microbiota in High-Fat Diet-Fed Mice 97:147 Crude Polysaccharide Extracted From Moringa oleifera Leaves Prevents Obesity in Association With Modulating Gut Microbiota in High-Fat Diet-Fed Mice. 35548566 0 11 with Association 80:90 arg1 Microbiota 112:121 Modulating Gut Microbiota 97:121 Modulating Gut Microbiota in High-Fat Diet-Fed Mice 97:147 Crude Polysaccharide Extracted From Moringa oleifera Leaves Prevents Obesity in Association With Modulating Gut Microbiota in High-Fat Diet-Fed Mice. 35548566 6 12 theme gut 870:872 arg1 composition 885:895 gut microbiota composition 870:895 gut microbiota composition 870:895 Physiological, histological, biochemical parameters, genes related to lipid metabolism, and gut microbiota composition were compared among five experimental groups. 35548566 0 13 theme Modulating 97:106 arg1 Microbiota 112:121 Modulating Gut Microbiota 97:121 Modulating Gut Microbiota in High-Fat Diet-Fed Mice 97:147 Crude Polysaccharide Extracted From Moringa oleifera Leaves Prevents Obesity in Association With Modulating Gut Microbiota in High-Fat Diet-Fed Mice. 35548566 5 14 theme normal 632:637 arg1 diet 644:647 a normal chow diet 630:647 a normal chow diet (NCD group) 630:659 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 5 14 theme normal 632:637 arg1 group 654:658 NCD group 650:658 NCD group 650:658 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 10 15 used used 1883:1886 arg2 prebiotic 1903:1911 a potential prebiotic 1891:1911 a potential prebiotic 1891:1911 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 10 15 used used 1883:1886 arg2 MOP 1872:1874 MOP 1872:1874 MOP 1872:1874 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 9 16 from obesity 1650:1656 arg1 mice 1661:1664 mice 1661:1664 mice 1661:1664 These results demonstrated that MOP supplementation has a protective effect against HFD-induced obesity in mice, which was associated with reshaping the gut microbiota. 35548566 3 17 theme M. 338:339 arg1 MOP 367:369 MOP 367:369 MOP 367:369 However, the biological activities of M. oleifera polysaccharides (MOP) in regulating gut microbiota and alleviating obesity remain obscure. 35548566 3 17 theme M. 338:339 arg1 polysaccharides 350:364 M. oleifera polysaccharides 338:364 M. oleifera polysaccharides (MOP) 338:370 However, the biological activities of M. oleifera polysaccharides (MOP) in regulating gut microbiota and alleviating obesity remain obscure. 35548566 5 18 from dose 729:732 arg1 MOP 710:712 MOP 710:712 MOP at a different dose of 100, 200, and 400 mg/kg/d 710:761 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 7 19 theme lipid 1220:1224 arg1 metabolism 1226:1235 lipid metabolism 1220:1235 lipid metabolism 1220:1235 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 2 20 theme food 276:279 arg1 resource 281:288 a new food resource 270:288 a new food resource in China 270:297 M. oleifera leaves are considered a new food resource in China. 35548566 7 21 theme bile 1241:1244 arg1 metabolism 1251:1260 bile acid metabolism 1241:1260 bile acid metabolism 1241:1260 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 3 22 theme oleifera 341:348 arg1 MOP 367:369 MOP 367:369 MOP 367:369 However, the biological activities of M. oleifera polysaccharides (MOP) in regulating gut microbiota and alleviating obesity remain obscure. 35548566 3 22 theme oleifera 341:348 arg1 polysaccharides 350:364 M. oleifera polysaccharides 338:364 M. oleifera polysaccharides (MOP) 338:370 However, the biological activities of M. oleifera polysaccharides (MOP) in regulating gut microbiota and alleviating obesity remain obscure. 35548566 8 23 theme Blautia 1475:1481 arg1 abundance 1462:1470 the relative abundance 1449:1470 the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity 1449:1551 In addition, MOP positively reshaped the gut microbiota composition, significantly increasing the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter, while decreasing the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity. 35548566 5 24 theme experimental 589:600 arg1 mice 602:605 The experimental mice 585:605 The experimental mice 585:605 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 7 25 theme MOP 967:969 arg1 supplementation 971:985 MOP supplementation 967:985 MOP supplementation 967:985 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 2 26 theme new 272:274 arg1 resource 281:288 a new food resource 270:288 a new food resource in China 270:297 M. oleifera leaves are considered a new food resource in China. 35548566 1 27 theme used 181:184 arg1 plant 186:190 a commonly used plant 170:190 a commonly used plant with high nutritional and medicinal values 170:233 Moringa oleifera is a commonly used plant with high nutritional and medicinal values. 35548566 1 27 theme used 181:184 arg1 oleifera 158:165 Moringa oleifera 150:165 Moringa oleifera 150:165 Moringa oleifera is a commonly used plant with high nutritional and medicinal values. 35548566 7 28 theme lipid 1078:1082 arg1 levels 1084:1089 blood lipid levels 1072:1089 blood lipid levels 1072:1089 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 9 29 theme gut 1707:1709 arg1 microbiota 1711:1720 the gut microbiota 1703:1720 the gut microbiota 1703:1720 These results demonstrated that MOP supplementation has a protective effect against HFD-induced obesity in mice, which was associated with reshaping the gut microbiota. 35548566 8 30 theme relative 1453:1460 arg1 abundance 1462:1470 the relative abundance 1449:1470 the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity 1449:1551 In addition, MOP positively reshaped the gut microbiota composition, significantly increasing the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter, while decreasing the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity. 35548566 6 31 theme lipid 848:852 arg1 metabolism 854:863 lipid metabolism 848:863 lipid metabolism 848:863 Physiological, histological, biochemical parameters, genes related to lipid metabolism, and gut microbiota composition were compared among five experimental groups. 35548566 0 32 theme Crude 0:4 arg1 Polysaccharide 6:19 Crude Polysaccharide 0:19 Crude Polysaccharide Extracted From Moringa oleifera 0:51 Crude Polysaccharide Extracted From Moringa oleifera Leaves Prevents Obesity in Association With Modulating Gut Microbiota in High-Fat Diet-Fed Mice. 35548566 8 33 theme Alistipes 1484:1492 arg1 abundance 1462:1470 the relative abundance 1449:1470 the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity 1449:1551 In addition, MOP positively reshaped the gut microbiota composition, significantly increasing the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter, while decreasing the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity. 35548566 5 34 theme high-fat 664:671 arg1 diet 673:676 a high-fat diet 662:676 a high-fat diet (HFD group) 662:688 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 5 34 theme high-fat 664:671 arg1 group 683:687 HFD group 679:687 HFD group 679:687 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 5 35 theme mg/kg/d 755:761 arg1 dose 729:732 a different dose 717:732 a different dose of 100, 200, and 400 mg/kg/d 717:761 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 5 36 theme different 719:727 arg1 dose 729:732 a different dose 717:732 a different dose of 100, 200, and 400 mg/kg/d 717:761 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 0 37 theme Diet-Fed 135:142 arg1 Mice 144:147 High-Fat Diet-Fed Mice 126:147 High-Fat Diet-Fed Mice 126:147 Crude Polysaccharide Extracted From Moringa oleifera Leaves Prevents Obesity in Association With Modulating Gut Microbiota in High-Fat Diet-Fed Mice. 35548566 8 38 theme microbiota 1308:1317 arg1 composition 1319:1329 the gut microbiota composition 1300:1329 the gut microbiota composition 1300:1329 In addition, MOP positively reshaped the gut microbiota composition, significantly increasing the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter, while decreasing the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity. 35548566 5 39 theme HFD 679:681 arg1 diet 673:676 a high-fat diet 662:676 a high-fat diet (HFD group) 662:688 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 5 39 theme HFD 679:681 arg1 group 683:687 HFD group 679:687 HFD group 679:687 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 1 40 theme high 197:200 arg1 values 228:233 high nutritional and medicinal values 197:233 high nutritional and medicinal values 197:233 Moringa oleifera is a commonly used plant with high nutritional and medicinal values. 35548566 7 41 theme blood 1072:1076 arg1 levels 1084:1089 blood lipid levels 1072:1089 blood lipid levels 1072:1089 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 4 42 theme high-fat 542:549 arg1 HFD 557:559 HFD 557:559 HFD 557:559 In the present study, we prepared the MOP and evaluated its effects on obesity and gut microbiota in high-fat diet (HFD)-induced C57BL/6J mice. 35548566 4 42 theme high-fat 542:549 arg1 diet 551:554 high-fat diet 542:554 high-fat diet (HFD) 542:560 In the present study, we prepared the MOP and evaluated its effects on obesity and gut microbiota in high-fat diet (HFD)-induced C57BL/6J mice. 35548566 0 43 theme High-Fat 126:133 arg1 Mice 144:147 High-Fat Diet-Fed Mice 126:147 High-Fat Diet-Fed Mice 126:147 Crude Polysaccharide Extracted From Moringa oleifera Leaves Prevents Obesity in Association With Modulating Gut Microbiota in High-Fat Diet-Fed Mice. 35548566 9 44 theme protective 1612:1621 arg1 effect 1623:1628 a protective effect 1610:1628 a protective effect 1610:1628 These results demonstrated that MOP supplementation has a protective effect against HFD-induced obesity in mice, which was associated with reshaping the gut microbiota. 35548566 10 45 theme MOP 1798:1800 arg1 potential 1785:1793 the potential 1781:1793 the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic 1781:1911 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 1 46 theme nutritional 202:212 arg1 values 228:233 high nutritional and medicinal values 197:233 high nutritional and medicinal values 197:233 Moringa oleifera is a commonly used plant with high nutritional and medicinal values. 35548566 7 47 theme related 1209:1215 arg1 genes 1203:1207 genes 1203:1207 genes related to lipid metabolism and bile acid metabolism 1203:1260 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 7 48 theme genes 1203:1207 arg1 expression 1189:1198 the expression 1185:1198 the expression of genes related to lipid metabolism and bile acid metabolism 1185:1260 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 8 49 theme gut 1304:1306 arg1 composition 1319:1329 the gut microbiota composition 1300:1329 the gut microbiota composition 1300:1329 In addition, MOP positively reshaped the gut microbiota composition, significantly increasing the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter, while decreasing the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity. 35548566 2 50 dep oleifera 239:246 arg1 leaves 248:253 leaves 248:253 leaves 248:253 M. oleifera leaves are considered a new food resource in China. 35548566 9 51 contain has 1606:1608 arg1 supplementation 1590:1604 MOP supplementation 1586:1604 MOP supplementation 1586:1604 These results demonstrated that MOP supplementation has a protective effect against HFD-induced obesity in mice, which was associated with reshaping the gut microbiota. 35548566 9 51 contain has 1606:1608 arg2 effect 1623:1628 a protective effect 1610:1628 a protective effect 1610:1628 These results demonstrated that MOP supplementation has a protective effect against HFD-induced obesity in mice, which was associated with reshaping the gut microbiota. 35548566 6 52 theme related 837:843 arg1 genes 831:835 genes 831:835 genes related to lipid metabolism 831:863 Physiological, histological, biochemical parameters, genes related to lipid metabolism, and gut microbiota composition were compared among five experimental groups. 35548566 10 53 theme gut 1836:1838 arg1 microbiota 1840:1849 gut microbiota 1836:1849 gut microbiota 1836:1849 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 0 54 dep Leaves 53:58 arg1 Prevents 60:67 Prevents 60:67 Leaves Prevents Obesity in Association With Modulating Gut Microbiota in High-Fat Diet-Fed Mice 53:147 Crude Polysaccharide Extracted From Moringa oleifera Leaves Prevents Obesity in Association With Modulating Gut Microbiota in High-Fat Diet-Fed Mice. 35548566 1 55 theme medicinal 218:226 arg1 values 228:233 high nutritional and medicinal values 197:233 high nutritional and medicinal values 197:233 Moringa oleifera is a commonly used plant with high nutritional and medicinal values. 35548566 3 56 theme gut 386:388 arg1 microbiota 390:399 gut microbiota 386:399 gut microbiota 386:399 However, the biological activities of M. oleifera polysaccharides (MOP) in regulating gut microbiota and alleviating obesity remain obscure. 35548566 3 57 theme polysaccharides 350:364 arg1 activities 324:333 the biological activities 309:333 the biological activities of M. oleifera polysaccharides (MOP) in regulating gut microbiota and alleviating obesity 309:423 However, the biological activities of M. oleifera polysaccharides (MOP) in regulating gut microbiota and alleviating obesity remain obscure. 35548566 1 58 with plant 186:190 arg1 values 228:233 high nutritional and medicinal values 197:233 high nutritional and medicinal values 197:233 Moringa oleifera is a commonly used plant with high nutritional and medicinal values. 35548566 4 59 theme present 448:454 arg1 study 456:460 the present study 444:460 the present study 444:460 In the present study, we prepared the MOP and evaluated its effects on obesity and gut microbiota in high-fat diet (HFD)-induced C57BL/6J mice. 35548566 4 60 from effects 501:507 arg1 obesity 512:518 obesity 512:518 obesity 512:518 In the present study, we prepared the MOP and evaluated its effects on obesity and gut microbiota in high-fat diet (HFD)-induced C57BL/6J mice. 35548566 4 60 from effects 501:507 arg1 mice 579:582 high-fat diet (HFD)-induced C57BL/6J mice 542:582 high-fat diet (HFD)-induced C57BL/6J mice 542:582 In the present study, we prepared the MOP and evaluated its effects on obesity and gut microbiota in high-fat diet (HFD)-induced C57BL/6J mice. 35548566 4 60 from effects 501:507 arg1 gut 524:526 gut 524:526 gut 524:526 In the present study, we prepared the MOP and evaluated its effects on obesity and gut microbiota in high-fat diet (HFD)-induced C57BL/6J mice. 35548566 7 61 theme insulin 1095:1101 arg1 resistance 1103:1112 insulin resistance 1095:1112 insulin resistance 1095:1112 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 7 62 theme weight 1009:1014 arg1 gain 1016:1019 weight gain 1009:1019 weight gain 1009:1019 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 7 63 theme acid 1246:1249 arg1 metabolism 1251:1260 bile acid metabolism 1241:1260 bile acid metabolism 1241:1260 The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. 35548566 9 64 theme HFD-induced 1638:1648 arg1 obesity 1650:1656 HFD-induced obesity 1638:1656 HFD-induced obesity in mice 1638:1664 These results demonstrated that MOP supplementation has a protective effect against HFD-induced obesity in mice, which was associated with reshaping the gut microbiota. 35548566 0 65 from Microbiota 112:121 arg1 Mice 144:147 High-Fat Diet-Fed Mice 126:147 High-Fat Diet-Fed Mice 126:147 Crude Polysaccharide Extracted From Moringa oleifera Leaves Prevents Obesity in Association With Modulating Gut Microbiota in High-Fat Diet-Fed Mice. 35548566 4 66 theme C57BL/6J 570:577 arg1 mice 579:582 high-fat diet (HFD)-induced C57BL/6J mice 542:582 high-fat diet (HFD)-induced C57BL/6J mice 542:582 In the present study, we prepared the MOP and evaluated its effects on obesity and gut microbiota in high-fat diet (HFD)-induced C57BL/6J mice. 35548566 5 67 theme NCD 650:652 arg1 diet 644:647 a normal chow diet 630:647 a normal chow diet (NCD group) 630:659 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 5 67 theme NCD 650:652 arg1 group 654:658 NCD group 650:658 NCD group 650:658 The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. 35548566 8 68 theme Oscillibacter 1417:1429 arg1 abundance 1361:1369 the abundance 1357:1369 the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter 1357:1429 In addition, MOP positively reshaped the gut microbiota composition, significantly increasing the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter, while decreasing the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity. 35548566 8 69 theme norank_f_Ruminococcaceae 1387:1410 arg1 abundance 1361:1369 the abundance 1357:1369 the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter 1357:1429 In addition, MOP positively reshaped the gut microbiota composition, significantly increasing the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter, while decreasing the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity. 35548566 4 70 theme -induced 561:568 arg1 mice 579:582 high-fat diet (HFD)-induced C57BL/6J mice 542:582 high-fat diet (HFD)-induced C57BL/6J mice 542:582 In the present study, we prepared the MOP and evaluated its effects on obesity and gut microbiota in high-fat diet (HFD)-induced C57BL/6J mice. 35548566 10 71 from report 1771:1776 arg1 potential 1785:1793 the potential 1781:1793 the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic 1781:1911 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 6 72 theme experimental 922:933 arg1 groups 935:940 five experimental groups 917:940 five experimental groups 917:940 Physiological, histological, biochemical parameters, genes related to lipid metabolism, and gut microbiota composition were compared among five experimental groups. 35548566 1 73 theme Moringa 150:156 arg1 plant 186:190 a commonly used plant 170:190 a commonly used plant with high nutritional and medicinal values 170:233 Moringa oleifera is a commonly used plant with high nutritional and medicinal values. 35548566 1 73 theme Moringa 150:156 arg1 oleifera 158:165 Moringa oleifera 150:165 Moringa oleifera 150:165 Moringa oleifera is a commonly used plant with high nutritional and medicinal values. 35548566 2 74 from resource 281:288 arg1 China 293:297 China 293:297 China 293:297 M. oleifera leaves are considered a new food resource in China. 35548566 6 75 theme biochemical 807:817 arg1 parameters 819:828 biochemical parameters 807:828 biochemical parameters 807:828 Physiological, histological, biochemical parameters, genes related to lipid metabolism, and gut microbiota composition were compared among five experimental groups. 35548566 10 76 theme potential 1893:1901 arg1 MOP 1872:1874 MOP 1872:1874 MOP 1872:1874 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 10 76 theme potential 1893:1901 arg1 prebiotic 1903:1911 a potential prebiotic 1891:1911 a potential prebiotic 1891:1911 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 10 77 theme first 1765:1769 arg1 this 1753:1756 this 1753:1756 this 1753:1756 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 10 77 theme first 1765:1769 arg1 report 1771:1776 the first report 1761:1776 the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic 1761:1911 To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic. 35548566 8 78 theme Tyzzerella 1499:1508 arg1 abundance 1462:1470 the relative abundance 1449:1470 the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity 1449:1551 In addition, MOP positively reshaped the gut microbiota composition, significantly increasing the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter, while decreasing the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity. 36431036 7 0 theme E 1065:1065 arg1 sp 1083:1084 E and Tetraselmis sp 1065:1084 E and Tetraselmis sp. 1065:1085 E and Tetraselmis sp. 36431036 1 1 theme antioxidant 168:178 arg1 compounds 202:210 antioxidant and anti-inflammatory compounds 168:210 antioxidant and anti-inflammatory compounds 168:210 Microalgae are known producers of antioxidant and anti-inflammatory compounds, making them natural alternatives to be used as food and feed functional ingredients. 36431036 12 2 theme protective 1352:1361 arg1 effect 1363:1368 a promising HBRC protective effect 1335:1368 a promising HBRC protective effect 1335:1368 W showed a promising HBRC protective effect and COX-2 inhibition. 36431036 2 3 theme commercial 368:377 arg1 value 379:383 commercial value 368:383 commercial value for four commercially available microalgae: Isochrysis galbana, Nannochloropsis sp., Tetraselmis sp., and Phaeodactylum tricornutum 368:515 This study aimed to valorise biomass and exploit new applications and commercial value for four commercially available microalgae: Isochrysis galbana, Nannochloropsis sp., Tetraselmis sp., and Phaeodactylum tricornutum. 36431036 12 4 theme HBRC 1347:1350 arg1 effect 1363:1368 a promising HBRC protective effect 1335:1368 a promising HBRC protective effect 1335:1368 W showed a promising HBRC protective effect and COX-2 inhibition. 36431036 6 5 theme ABTS•+ 1037:1042 arg1 Nannochloropsis 1045:1059 Nannochloropsis 1045:1059 Nannochloropsis 1045:1059 The results of antioxidant assays revealed the potential of some microalgae extracts: in ABTS•+, Nannochloropsis sp. 36431036 6 5 theme ABTS•+ 1037:1042 arg1 sp 1061:1062 ABTS•+, Nannochloropsis sp 1037:1062 sp 1061:1062 The results of antioxidant assays revealed the potential of some microalgae extracts: in ABTS•+, Nannochloropsis sp. 36431036 8 6 from P 1097:1097 arg1 DPPH• 1103:1107 DPPH• 1103:1107 DPPH• 1103:1107 A, E, and P; in DPPH•, Tetraselmis sp. 36431036 5 7 dep composition 770:780 arg1 carbohydrates 783:795 carbohydrates 783:795 carbohydrates 783:795 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 5 7 dep composition 770:780 arg1 proteins 806:813 soluble proteins 798:813 soluble proteins 798:813 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 5 7 dep composition 770:780 arg1 lipids 820:825 lipids 820:825 lipids 820:825 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 4 8 theme extracts 722:729 arg1 ABTS•+/DPPH•/•NO/O2•-/ORAC-FL 640:668 ABTS•+/DPPH•/•NO/O2•-/ORAC-FL 640:668 ABTS•+/DPPH•/•NO/O2•-/ORAC-FL 640:668 The antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) and anti-inflammatory capacity (HBRC/COX-2) of the extracts were screened. 36431036 4 8 theme extracts 722:729 arg1 HBRC/COX-2 703:712 HBRC/COX-2 703:712 HBRC/COX-2 703:712 The antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) and anti-inflammatory capacity (HBRC/COX-2) of the extracts were screened. 36431036 4 8 theme extracts 722:729 arg1 capacity 630:637 antioxidant capacity 618:637 antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) 618:669 The antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) and anti-inflammatory capacity (HBRC/COX-2) of the extracts were screened. 36431036 4 8 theme extracts 722:729 arg1 capacity 693:700 anti-inflammatory capacity 675:700 anti-inflammatory capacity (HBRC/COX-2) 675:713 The antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) and anti-inflammatory capacity (HBRC/COX-2) of the extracts were screened. 36431036 1 9 theme functional 274:283 arg1 ingredients 285:295 functional ingredients 274:295 functional ingredients 274:295 Microalgae are known producers of antioxidant and anti-inflammatory compounds, making them natural alternatives to be used as food and feed functional ingredients. 36431036 0 10 theme Antioxidant 89:99 arg1 Compounds 123:131 Antioxidant and Anti-Inflammatory Compounds 89:131 Antioxidant and Anti-Inflammatory Compounds 89:131 Potential of Microalgae Extracts for Food and Feed Supplementation-A Promising Source of Antioxidant and Anti-Inflammatory Compounds. 36431036 3 11 dep ethanol 570:576 arg1 water 602:606 water 602:606 water (EW) 602:611 For that, five extracts were obtained: acetone (A), ethanol (E), water (W), ethanol:water (EW). 36431036 3 11 dep ethanol 570:576 arg1 EW 609:610 EW 609:610 EW 609:610 For that, five extracts were obtained: acetone (A), ethanol (E), water (W), ethanol:water (EW). 36431036 10 12 dep and 1196:1198 arg1 W 1193:1193 W 1193:1193 W 1193:1193 W; and in ORAC-FL, I. galbana EW and P. tricornutum EW. 36431036 4 13 theme anti-inflammatory 675:691 arg1 HBRC/COX-2 703:712 HBRC/COX-2 703:712 HBRC/COX-2 703:712 The antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) and anti-inflammatory capacity (HBRC/COX-2) of the extracts were screened. 36431036 4 13 theme anti-inflammatory 675:691 arg1 capacity 693:700 anti-inflammatory capacity 675:700 anti-inflammatory capacity (HBRC/COX-2) 675:713 The antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) and anti-inflammatory capacity (HBRC/COX-2) of the extracts were screened. 36431036 0 14 theme Compounds 123:131 arg1 Source 79:84 Promising Source 69:84 Promising Source of Antioxidant and Anti-Inflammatory Compounds 69:131 Potential of Microalgae Extracts for Food and Feed Supplementation-A Promising Source of Antioxidant and Anti-Inflammatory Compounds. 36431036 11 15 theme anti-inflammatory 1260:1276 arg1 capacity 1278:1285 anti-inflammatory capacity 1260:1285 anti-inflammatory capacity 1260:1285 Concerning anti-inflammatory capacity, P. tricornutum EW and Tetraselmis sp. 36431036 4 16 dep capacity 630:637 arg1 The 614:616 The 614:616 The 614:616 The antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) and anti-inflammatory capacity (HBRC/COX-2) of the extracts were screened. 36431036 6 17 theme microalgae 1013:1022 arg1 extracts 1024:1031 some microalgae extracts 1008:1031 some microalgae extracts 1008:1031 The results of antioxidant assays revealed the potential of some microalgae extracts: in ABTS•+, Nannochloropsis sp. 36431036 1 18 theme anti-inflammatory 184:200 arg1 compounds 202:210 antioxidant and anti-inflammatory compounds 168:210 antioxidant and anti-inflammatory compounds 168:210 Microalgae are known producers of antioxidant and anti-inflammatory compounds, making them natural alternatives to be used as food and feed functional ingredients. 36431036 0 19 theme Anti-Inflammatory 105:121 arg1 Compounds 123:131 Antioxidant and Anti-Inflammatory Compounds 89:131 Antioxidant and Anti-Inflammatory Compounds 89:131 Potential of Microalgae Extracts for Food and Feed Supplementation-A Promising Source of Antioxidant and Anti-Inflammatory Compounds. 36431036 5 20 theme extracts 922:929 arg1 compounds 861:869 bioactive compounds 851:869 bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts 851:929 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 1 21 theme compounds 202:210 arg1 Microalgae 134:143 Microalgae 134:143 Microalgae 134:143 Microalgae are known producers of antioxidant and anti-inflammatory compounds, making them natural alternatives to be used as food and feed functional ingredients. 36431036 1 21 theme compounds 202:210 arg1 producers 155:163 known producers 149:163 known producers of antioxidant and anti-inflammatory compounds 149:210 Microalgae are known producers of antioxidant and anti-inflammatory compounds, making them natural alternatives to be used as food and feed functional ingredients. 36431036 5 22 theme phenolic 885:892 arg1 compounds 894:902 phenolic compounds 885:902 phenolic compounds 885:902 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 2 23 theme available 407:415 arg1 microalgae 417:426 four commercially available microalgae 389:426 four commercially available microalgae: Isochrysis galbana, Nannochloropsis sp., Tetraselmis sp., and Phaeodactylum tricornutum 389:515 This study aimed to valorise biomass and exploit new applications and commercial value for four commercially available microalgae: Isochrysis galbana, Nannochloropsis sp., Tetraselmis sp., and Phaeodactylum tricornutum. 36431036 9 24 theme Tetraselmis 1177:1187 arg1 A 1126:1126 A 1126:1126 A 1126:1126 A and E; in •NO, P. tricornutum E and EW; in O2•-, Tetraselmis sp. 36431036 9 24 theme Tetraselmis 1177:1187 arg1 sp 1189:1190 Tetraselmis sp 1177:1190 Tetraselmis sp 1177:1190 A and E; in •NO, P. tricornutum E and EW; in O2•-, Tetraselmis sp. 36431036 13 25 theme Tetraselmis 1399:1409 arg1 sp 1411:1412 Tetraselmis sp 1399:1412 Tetraselmis sp 1399:1412 Hence, Tetraselmis sp. 36431036 0 26 theme Extracts 24:31 arg1 Potential 0:8 Potential 0:8 Potential of Microalgae Extracts for Food and Feed 0:49 Potential of Microalgae Extracts for Food and Feed Supplementation-A Promising Source of Antioxidant and Anti-Inflammatory Compounds. 36431036 6 27 from potential 995:1003 arg1 Nannochloropsis 1045:1059 Nannochloropsis 1045:1059 Nannochloropsis 1045:1059 The results of antioxidant assays revealed the potential of some microalgae extracts: in ABTS•+, Nannochloropsis sp. 36431036 6 27 from potential 995:1003 arg1 sp 1061:1062 ABTS•+, Nannochloropsis sp 1037:1062 sp 1061:1062 The results of antioxidant assays revealed the potential of some microalgae extracts: in ABTS•+, Nannochloropsis sp. 36431036 14 28 contain have 1451:1454 arg2 potential 1456:1464 potential 1456:1464 potential 1456:1464 and P. tricornutum extracts seem to have potential to be incorporated as feed and food functional ingredients and preservatives. 36431036 14 28 contain have 1451:1454 arg1 extracts 1434:1441 and P. tricornutum extracts 1415:1441 extracts 1434:1441 and P. tricornutum extracts seem to have potential to be incorporated as feed and food functional ingredients and preservatives. 36431036 5 29 theme soluble 798:804 arg1 proteins 806:813 soluble proteins 798:813 soluble proteins 798:813 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 0 30 theme Microalgae 13:22 arg1 Extracts 24:31 Microalgae Extracts 13:31 Microalgae Extracts 13:31 Potential of Microalgae Extracts for Food and Feed Supplementation-A Promising Source of Antioxidant and Anti-Inflammatory Compounds. 36431036 5 31 dep compounds 861:869 arg1 carotenoids 872:882 carotenoids 872:882 carotenoids 872:882 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 5 31 dep compounds 861:869 arg1 compounds 894:902 phenolic compounds 885:902 phenolic compounds 885:902 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 5 31 dep compounds 861:869 arg1 peptides 909:916 peptides 909:916 peptides 909:916 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 8 32 from A 1087:1087 arg1 DPPH• 1103:1107 DPPH• 1103:1107 DPPH• 1103:1107 A, E, and P; in DPPH•, Tetraselmis sp. 36431036 5 33 theme bioactive 851:859 arg1 compounds 861:869 bioactive compounds 851:869 bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts 851:929 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 1 34 theme natural 225:231 arg1 alternatives 233:244 natural alternatives 225:244 natural alternatives 225:244 Microalgae are known producers of antioxidant and anti-inflammatory compounds, making them natural alternatives to be used as food and feed functional ingredients. 36431036 8 35 theme Tetraselmis 1110:1120 arg1 A 1087:1087 A 1087:1087 A 1087:1087 A, E, and P; in DPPH•, Tetraselmis sp. 36431036 8 35 theme Tetraselmis 1110:1120 arg1 sp 1122:1123 Tetraselmis sp 1110:1123 Tetraselmis sp 1110:1123 A, E, and P; in DPPH•, Tetraselmis sp. 36431036 1 36 dep food 260:263 arg1 ingredients 285:295 functional ingredients 274:295 functional ingredients 274:295 Microalgae are known producers of antioxidant and anti-inflammatory compounds, making them natural alternatives to be used as food and feed functional ingredients. 36431036 11 37 theme Tetraselmis 1310:1320 arg1 sp 1322:1323 Tetraselmis sp 1310:1323 Tetraselmis sp 1310:1323 Concerning anti-inflammatory capacity, P. tricornutum EW and Tetraselmis sp. 36431036 12 38 theme promising 1337:1345 arg1 effect 1363:1368 a promising HBRC protective effect 1335:1368 a promising HBRC protective effect 1335:1368 W showed a promising HBRC protective effect and COX-2 inhibition. 36431036 5 39 theme general 750:756 arg1 composition 770:780 The general biochemical composition 746:780 The general biochemical composition (carbohydrates, soluble proteins, and lipids) 746:826 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 9 40 from E 1132:1132 arg1 •NO 1138:1140 •NO 1138:1140 •NO 1138:1140 A and E; in •NO, P. tricornutum E and EW; in O2•-, Tetraselmis sp. 36431036 9 40 from E 1132:1132 arg1 EW 1164:1165 EW 1164:1165 EW 1164:1165 A and E; in •NO, P. tricornutum E and EW; in O2•-, Tetraselmis sp. 36431036 9 40 from E 1132:1132 arg1 E 1158:1158 E 1158:1158 E 1158:1158 A and E; in •NO, P. tricornutum E and EW; in O2•-, Tetraselmis sp. 36431036 12 41 theme COX-2 1374:1378 arg1 inhibition 1380:1389 COX-2 inhibition 1374:1389 COX-2 inhibition 1374:1389 W showed a promising HBRC protective effect and COX-2 inhibition. 36431036 5 42 theme compounds 861:869 arg1 compounds 861:869 bioactive compounds 851:869 bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts 851:929 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 5 42 theme compounds 861:869 arg1 groups 841:846 the main groups 832:846 the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts 832:929 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 5 42 theme compounds 861:869 arg1 composition 770:780 The general biochemical composition 746:780 The general biochemical composition (carbohydrates, soluble proteins, and lipids) 746:826 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 5 43 theme biochemical 758:768 arg1 composition 770:780 The general biochemical composition 746:780 The general biochemical composition (carbohydrates, soluble proteins, and lipids) 746:826 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 14 44 theme functional 1502:1511 arg1 ingredients 1513:1523 feed and food functional ingredients 1488:1523 feed and food functional ingredients 1488:1523 and P. tricornutum extracts seem to have potential to be incorporated as feed and food functional ingredients and preservatives. 36431036 14 45 theme food 1497:1500 arg1 ingredients 1513:1523 feed and food functional ingredients 1488:1523 feed and food functional ingredients 1488:1523 and P. tricornutum extracts seem to have potential to be incorporated as feed and food functional ingredients and preservatives. 36431036 2 46 theme new 347:349 arg1 applications 351:362 new applications 347:362 new applications 347:362 This study aimed to valorise biomass and exploit new applications and commercial value for four commercially available microalgae: Isochrysis galbana, Nannochloropsis sp., Tetraselmis sp., and Phaeodactylum tricornutum. 36431036 6 47 theme assays 975:980 arg1 results 952:958 The results 948:958 The results of antioxidant assays 948:980 The results of antioxidant assays revealed the potential of some microalgae extracts: in ABTS•+, Nannochloropsis sp. 36431036 8 48 from E 1090:1090 arg1 DPPH• 1103:1107 DPPH• 1103:1107 DPPH• 1103:1107 A, E, and P; in DPPH•, Tetraselmis sp. 36431036 14 49 dep P. 1419:1420 arg1 tricornutum 1422:1432 tricornutum 1422:1432 tricornutum 1422:1432 and P. tricornutum extracts seem to have potential to be incorporated as feed and food functional ingredients and preservatives. 36431036 1 50 theme known 149:153 arg1 Microalgae 134:143 Microalgae 134:143 Microalgae 134:143 Microalgae are known producers of antioxidant and anti-inflammatory compounds, making them natural alternatives to be used as food and feed functional ingredients. 36431036 1 50 theme known 149:153 arg1 producers 155:163 known producers 149:163 known producers of antioxidant and anti-inflammatory compounds 149:210 Microalgae are known producers of antioxidant and anti-inflammatory compounds, making them natural alternatives to be used as food and feed functional ingredients. 36431036 6 51 theme antioxidant 963:973 arg1 assays 975:980 antioxidant assays 963:980 antioxidant assays 963:980 The results of antioxidant assays revealed the potential of some microalgae extracts: in ABTS•+, Nannochloropsis sp. 36431036 0 52 theme Promising 69:77 arg1 Source 79:84 Promising Source 69:84 Promising Source of Antioxidant and Anti-Inflammatory Compounds 69:131 Potential of Microalgae Extracts for Food and Feed Supplementation-A Promising Source of Antioxidant and Anti-Inflammatory Compounds. 36431036 14 53 theme feed 1488:1491 arg1 ingredients 1513:1523 feed and food functional ingredients 1488:1523 feed and food functional ingredients 1488:1523 and P. tricornutum extracts seem to have potential to be incorporated as feed and food functional ingredients and preservatives. 36431036 5 54 theme main 836:839 arg1 groups 841:846 the main groups 832:846 the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts 832:929 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 5 54 theme main 836:839 arg1 compounds 861:869 bioactive compounds 851:869 bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts 851:929 The general biochemical composition (carbohydrates, soluble proteins, and lipids) and the main groups of bioactive compounds (carotenoids, phenolic compounds, and peptides) of extracts were quantified. 36431036 6 55 theme extracts 1024:1031 arg1 potential 995:1003 the potential 991:1003 the potential of some microalgae extracts: in ABTS•+, Nannochloropsis sp 991:1062 The results of antioxidant assays revealed the potential of some microalgae extracts: in ABTS•+, Nannochloropsis sp. 36431036 7 56 theme Tetraselmis 1071:1081 arg1 sp 1083:1084 E and Tetraselmis sp 1065:1084 E and Tetraselmis sp. 1065:1085 E and Tetraselmis sp. 36431036 2 57 dep microalgae 417:426 arg1 galbana 440:446 Isochrysis galbana 429:446 Isochrysis galbana 429:446 This study aimed to valorise biomass and exploit new applications and commercial value for four commercially available microalgae: Isochrysis galbana, Nannochloropsis sp., Tetraselmis sp., and Phaeodactylum tricornutum. 36431036 2 57 dep microalgae 417:426 arg1 sp. 465:467 Nannochloropsis sp. 449:467 Nannochloropsis sp. 449:467 This study aimed to valorise biomass and exploit new applications and commercial value for four commercially available microalgae: Isochrysis galbana, Nannochloropsis sp., Tetraselmis sp., and Phaeodactylum tricornutum. 36431036 2 57 dep microalgae 417:426 arg1 sp. 482:484 Tetraselmis sp. 470:484 Tetraselmis sp. 470:484 This study aimed to valorise biomass and exploit new applications and commercial value for four commercially available microalgae: Isochrysis galbana, Nannochloropsis sp., Tetraselmis sp., and Phaeodactylum tricornutum. 36431036 2 57 dep microalgae 417:426 arg1 tricornutum 505:515 Phaeodactylum tricornutum 491:515 Phaeodactylum tricornutum 491:515 This study aimed to valorise biomass and exploit new applications and commercial value for four commercially available microalgae: Isochrysis galbana, Nannochloropsis sp., Tetraselmis sp., and Phaeodactylum tricornutum. 36431036 14 58 dep extracts 1434:1441 arg1 P. 1419:1420 P. 1419:1420 P. 1419:1420 and P. tricornutum extracts seem to have potential to be incorporated as feed and food functional ingredients and preservatives. 36431036 4 59 theme antioxidant 618:628 arg1 ABTS•+/DPPH•/•NO/O2•-/ORAC-FL 640:668 ABTS•+/DPPH•/•NO/O2•-/ORAC-FL 640:668 ABTS•+/DPPH•/•NO/O2•-/ORAC-FL 640:668 The antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) and anti-inflammatory capacity (HBRC/COX-2) of the extracts were screened. 36431036 4 59 theme antioxidant 618:628 arg1 capacity 630:637 antioxidant capacity 618:637 antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) 618:669 The antioxidant capacity (ABTS•+/DPPH•/•NO/O2•-/ORAC-FL) and anti-inflammatory capacity (HBRC/COX-2) of the extracts were screened. 36431036 9 60 from A 1126:1126 arg1 •NO 1138:1140 •NO 1138:1140 •NO 1138:1140 A and E; in •NO, P. tricornutum E and EW; in O2•-, Tetraselmis sp. 36431036 9 60 from A 1126:1126 arg1 EW 1164:1165 EW 1164:1165 EW 1164:1165 A and E; in •NO, P. tricornutum E and EW; in O2•-, Tetraselmis sp. 36431036 9 60 from A 1126:1126 arg1 E 1158:1158 E 1158:1158 E 1158:1158 A and E; in •NO, P. tricornutum E and EW; in O2•-, Tetraselmis sp. 36185697 0 0 theme antitumor 77:85 arg1 activity 87:94 antitumor activity 77:94 antitumor activity in vitro 77:103 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 36185697 5 1 theme cells 1295:1299 arg1 metastasis 1275:1284 metastasis 1275:1284 metastasis 1275:1284 Cell scratching and Transwell revealed that BJP-2 was able to block the invasion and metastasis of tumor cells. 36185697 5 1 theme cells 1295:1299 arg1 invasion 1262:1269 invasion 1262:1269 invasion 1262:1269 Cell scratching and Transwell revealed that BJP-2 was able to block the invasion and metastasis of tumor cells. 36185697 7 2 theme preventive 1603:1612 arg1 prospects 1582:1590 broad research prospects 1567:1590 broad research prospects 1567:1590 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 7 2 theme preventive 1603:1612 arg1 agent 1629:1633 a tumor preventive or therapeutic agent 1595:1633 a tumor preventive or therapeutic agent 1595:1633 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 6 3 theme Caspase-3/Caspase-3 1465:1483 arg1 downregulation 1521:1534 downregulation 1521:1534 downregulation of Bcl-2 1521:1543 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 6 3 theme Caspase-3/Caspase-3 1465:1483 arg1 overexpression 1434:1447 overexpression 1434:1447 overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 1434:1515 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 6 4 theme Cleaved 1457:1463 arg1 Caspase-3/Caspase-3 1465:1483 Cleaved Caspase-3/Caspase-3 1457:1483 Cleaved Caspase-3/Caspase-3 1457:1483 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 5 5 theme Cell 1190:1193 arg1 scratching 1195:1204 Cell scratching 1190:1204 Cell scratching 1190:1204 Cell scratching and Transwell revealed that BJP-2 was able to block the invasion and metastasis of tumor cells. 36185697 6 6 theme antitumor 1357:1365 arg1 activity 1367:1374 antitumor activity 1357:1374 antitumor activity 1357:1374 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 2 7 theme chromatographic 313:327 arg1 purification 329:340 chromatographic purification 313:340 chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column 313:394 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. 36185697 3 8 from effect 944:949 arg1 apoptosis 967:975 the apoptosis 963:975 the apoptosis of HepG2 cells and its anti-tumor mechanism 963:1019 The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism were further explored. 36185697 2 9 theme blackened 257:265 arg1 jujube 267:272 blackened jujube 257:272 blackened jujube 257:272 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. 36185697 4 10 theme cell 1112:1115 arg1 proliferation 1117:1129 cell proliferation 1112:1129 cell proliferation 1112:1129 The analysis by MTT and flow cytometry showed that BJP-2 suppressed cell proliferation by inducing apoptosis in a concentration-dependent manner. 36185697 6 11 theme Bax 1452:1454 arg1 downregulation 1521:1534 downregulation 1521:1534 downregulation of Bcl-2 1521:1543 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 6 11 theme Bax 1452:1454 arg1 overexpression 1434:1447 overexpression 1434:1447 overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 1434:1515 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 0 12 from jujube 45:50 arg1 polysaccharide 15:28 A novel acidic polysaccharide 0:28 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 0:104 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 36185697 1 13 theme cancers 145:151 arg1 cancers 145:151 the most common cancers 129:151 the most common cancers 129:151 Liver cancer is one of the most common cancers, with increasing trends in incidence and mortality. 36185697 1 13 theme cancers 145:151 arg1 one 122:124 one 122:124 one 122:124 Liver cancer is one of the most common cancers, with increasing trends in incidence and mortality. 36185697 3 14 theme anti-tumor 1000:1009 arg1 mechanism 1011:1019 its anti-tumor mechanism 996:1019 its anti-tumor mechanism 996:1019 The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism were further explored. 36185697 2 15 theme Sephadex 374:381 arg1 column 389:394 Sephadex G-100 column 374:394 Sephadex G-100 column 374:394 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. 36185697 0 16 theme novel 2:6 arg1 polysaccharide 15:28 A novel acidic polysaccharide 0:28 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 0:104 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 36185697 7 17 contain has 1563:1565 arg2 prospects 1582:1590 broad research prospects 1567:1590 broad research prospects 1567:1590 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 7 17 contain has 1563:1565 arg1 BJP-2 1557:1561 BJP-2 1557:1561 BJP-2 1557:1561 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 7 17 contain has 1563:1565 arg2 agent 1629:1633 a tumor preventive or therapeutic agent 1595:1633 a tumor preventive or therapeutic agent 1595:1633 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 4 18 theme flow 1068:1071 arg1 cytometry 1073:1081 flow cytometry 1068:1081 flow cytometry 1068:1081 The analysis by MTT and flow cytometry showed that BJP-2 suppressed cell proliferation by inducing apoptosis in a concentration-dependent manner. 36185697 6 19 theme blot 1310:1313 arg1 results 1315:1321 Western blot results 1302:1321 Western blot results 1302:1321 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 3 20 theme BJP-2 954:958 arg1 effect 944:949 The effect 940:949 The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism 940:1019 The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism were further explored. 36185697 6 21 theme Western 1302:1308 arg1 results 1315:1321 Western blot results 1302:1321 Western blot results 1302:1321 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 3 22 theme HepG2 980:984 arg1 cells 986:990 HepG2 cells 980:990 HepG2 cells 980:990 The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism were further explored. 36185697 0 23 theme acidic 8:13 arg1 polysaccharide 15:28 A novel acidic polysaccharide 0:28 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 0:104 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 36185697 6 24 theme Bcl-2 1539:1543 arg1 downregulation 1521:1534 downregulation 1521:1534 downregulation of Bcl-2 1521:1543 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 6 24 theme Bcl-2 1539:1543 arg1 overexpression 1434:1447 overexpression 1434:1447 overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 1434:1515 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 7 25 theme research 1573:1580 arg1 prospects 1582:1590 broad research prospects 1567:1590 broad research prospects 1567:1590 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 7 25 theme research 1573:1580 arg1 agent 1629:1633 a tumor preventive or therapeutic agent 1595:1633 a tumor preventive or therapeutic agent 1595:1633 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 1 26 theme common 138:143 arg1 cancers 145:151 the most common cancers 129:151 the most common cancers 129:151 Liver cancer is one of the most common cancers, with increasing trends in incidence and mortality. 36185697 3 27 theme cells 986:990 arg1 apoptosis 967:975 the apoptosis 963:975 the apoptosis of HepG2 cells and its anti-tumor mechanism 963:1019 The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism were further explored. 36185697 0 28 theme blackened 35:43 arg1 jujube 45:50 blackened jujube 35:50 blackened jujube 35:50 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 36185697 2 29 theme novel 207:211 arg1 polysaccharide 220:233 A novel acidic polysaccharide 205:233 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube 205:272 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. 36185697 2 29 theme novel 207:211 arg1 BJP-2 236:240 BJP-2 236:240 BJP-2 236:240 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. 36185697 2 30 theme G-100 383:387 arg1 column 389:394 Sephadex G-100 column 374:394 Sephadex G-100 column 374:394 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. 36185697 4 31 theme concentration-dependent 1158:1180 arg1 manner 1182:1187 a concentration-dependent manner 1156:1187 a concentration-dependent manner 1156:1187 The analysis by MTT and flow cytometry showed that BJP-2 suppressed cell proliferation by inducing apoptosis in a concentration-dependent manner. 36185697 5 32 theme tumor 1289:1293 arg1 cells 1295:1299 tumor cells 1289:1299 tumor cells 1289:1299 Cell scratching and Transwell revealed that BJP-2 was able to block the invasion and metastasis of tumor cells. 36185697 1 33 theme Liver 106:110 arg1 cancer 112:117 Liver cancer 106:117 Liver cancer 106:117 Liver cancer is one of the most common cancers, with increasing trends in incidence and mortality. 36185697 6 34 theme Caspase-9/Caspase-9 1497:1515 arg1 downregulation 1521:1534 downregulation 1521:1534 downregulation of Bcl-2 1521:1543 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 6 34 theme Caspase-9/Caspase-9 1497:1515 arg1 overexpression 1434:1447 overexpression 1434:1447 overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 1434:1515 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 7 35 theme therapeutic 1617:1627 arg1 prospects 1582:1590 broad research prospects 1567:1590 broad research prospects 1567:1590 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 7 35 theme therapeutic 1617:1627 arg1 agent 1629:1633 a tumor preventive or therapeutic agent 1595:1633 a tumor preventive or therapeutic agent 1595:1633 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 6 36 theme mitochondria-dependent 1386:1407 arg1 pathway 1409:1415 a mitochondria-dependent pathway 1384:1415 a mitochondria-dependent pathway 1384:1415 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 1 37 from trends 170:175 arg1 mortality 194:202 mortality 194:202 mortality 194:202 Liver cancer is one of the most common cancers, with increasing trends in incidence and mortality. 36185697 1 37 from trends 170:175 arg1 incidence 180:188 incidence 180:188 incidence 180:188 Liver cancer is one of the most common cancers, with increasing trends in incidence and mortality. 36185697 3 38 theme mechanism 1011:1019 arg1 apoptosis 967:975 the apoptosis 963:975 the apoptosis of HepG2 cells and its anti-tumor mechanism 963:1019 The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism were further explored. 36185697 6 39 theme Cleaved 1489:1495 arg1 Caspase-9/Caspase-9 1497:1515 Cleaved Caspase-9/Caspase-9 1489:1515 Cleaved Caspase-9/Caspase-9 1489:1515 Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. 36185697 0 40 dep polysaccharide 15:28 arg1 features 64:71 Structural features 53:71 Structural features 53:71 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 36185697 0 40 dep polysaccharide 15:28 arg1 activity 87:94 antitumor activity 77:94 antitumor activity in vitro 77:103 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 36185697 5 41 dep invasion 1262:1269 arg1 the 1258:1260 the 1258:1260 the 1258:1260 Cell scratching and Transwell revealed that BJP-2 was able to block the invasion and metastasis of tumor cells. 36185697 2 42 theme hot 291:293 arg1 water 295:299 hot water 291:299 hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column 291:394 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. 36185697 7 43 theme broad 1567:1571 arg1 prospects 1582:1590 broad research prospects 1567:1590 broad research prospects 1567:1590 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 7 43 theme broad 1567:1571 arg1 agent 1629:1633 a tumor preventive or therapeutic agent 1595:1633 a tumor preventive or therapeutic agent 1595:1633 Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent. 36185697 0 44 theme Structural 53:62 arg1 features 64:71 Structural features 53:71 Structural features 53:71 A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro. 36185697 2 45 theme acidic 213:218 arg1 polysaccharide 220:233 A novel acidic polysaccharide 205:233 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube 205:272 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. 36185697 2 45 theme acidic 213:218 arg1 BJP-2 236:240 BJP-2 236:240 BJP-2 236:240 A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. 37178294 11 0 theme atmospheric 2144:2154 arg1 particles 2166:2174 atmospheric composite particles 2144:2174 atmospheric composite particles closer to the real environment 2144:2205 The findings are expected to provide basic data for the mechanism research of atmospheric composite particles closer to the real environment. 37178294 7 1 dep complexation 1792:1803 arg1 force 1826:1830 force 1826:1830 force 1826:1830 The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. 37178294 1 2 theme calcite 270:276 arg1 particles 278:286 calcite particles 270:286 calcite particles 270:286 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 6 3 theme polysaccharides 1545:1559 arg1 characteristics 1459:1473 the infrared characteristics 1446:1473 the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria 1446:1598 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 9 4 theme bacterial 1949:1957 arg1 proteins 1967:1974 bacterial surface proteins 1949:1974 bacterial surface proteins 1949:1974 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 11 5 theme particles 2166:2174 arg1 research 2132:2139 the mechanism research 2118:2139 the mechanism research of atmospheric composite particles closer to the real environment 2118:2205 The findings are expected to provide basic data for the mechanism research of atmospheric composite particles closer to the real environment. 37178294 7 6 theme hydrogen 1809:1816 arg1 bonding 1818:1824 hydrogen bonding 1809:1824 hydrogen bonding 1809:1824 The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. 37178294 9 7 theme proteins 1967:1974 arg1 stable 1985:1990 stable 1985:1990 stable 1985:1990 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 9 7 theme proteins 1967:1974 arg1 structure 1936:1944 the secondary structure 1922:1944 the secondary structure of bacterial surface proteins 1922:1974 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 1 8 theme calcite/bacteria 200:215 arg1 complex 217:223 the calcite/bacteria complex 196:223 the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system 196:386 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 6 9 theme interfacial 1503:1513 arg1 interaction 1515:1525 the interfacial interaction 1499:1525 the interfacial interaction from the protein 1499:1542 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 7 10 theme complex 1652:1658 arg1 action 1617:1622 The interfacial action 1601:1622 The interfacial action of the micro-CaCO3/bacteria complex 1601:1658 The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. 37178294 4 11 theme 2.07 ~ 192.4 887:898 arg1 times 900:904 times 900:904 times 900:904 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 4 11 theme 2.07 ~ 192.4 887:898 arg1 size 872:875 The complex's particle size 849:875 The complex's particle size 849:875 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 4 12 dep times 900:904 arg1 larger 906:911 larger 906:911 larger 906:911 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 6 13 theme particles 1420:1428 arg1 characteristics 1393:1407 the infrared characteristics 1380:1407 the infrared characteristics of calcite particles 1380:1428 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 1 14 theme research 232:239 arg1 object 241:246 the research object 228:246 the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system 228:386 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 9 15 theme hydrogen 2000:2007 arg1 strong 2025:2030 strong 2025:2030 strong 2025:2030 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 9 15 theme hydrogen 2000:2007 arg1 effect 2014:2019 the hydrogen bond effect 1996:2019 the hydrogen bond effect 1996:2019 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 3 16 theme adhering 722:729 arg1 bacteria 713:720 bacteria 713:720 bacteria 713:720 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 6 17 theme bacteria 1591:1598 arg1 bacteria 1478:1485 bacteria 1478:1485 bacteria 1478:1485 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 6 17 theme bacteria 1591:1598 arg1 groups 1581:1586 phosphodiester groups 1566:1586 phosphodiester groups of bacteria 1566:1598 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 6 17 theme bacteria 1591:1598 arg1 bacteria 1591:1598 bacteria 1591:1598 bacteria 1591:1598 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 6 17 theme bacteria 1591:1598 arg1 polysaccharides 1545:1559 polysaccharides 1545:1559 polysaccharides 1545:1559 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 4 18 theme particle 863:870 arg1 times 900:904 times 900:904 times 900:904 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 4 18 theme particle 863:870 arg1 size 872:875 The complex's particle size 849:875 The complex's particle size 849:875 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 5 19 theme complex 1263:1269 arg1 potential 1226:1234 the surface potential 1214:1234 the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) 1214:1298 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 6 20 theme groups 1581:1586 arg1 characteristics 1459:1473 the infrared characteristics 1446:1473 the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria 1446:1598 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 1 21 theme atmospheric 146:156 arg1 aerosol 168:174 atmospheric microbial aerosol 146:174 atmospheric microbial aerosol 146:174 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 4 22 theme mineral 931:937 arg1 particles 939:947 the original mineral particles 918:947 the original mineral particles 918:947 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 11 23 theme mechanism 2122:2130 arg1 research 2132:2139 the mechanism research 2118:2139 the mechanism research of atmospheric composite particles closer to the real environment 2118:2205 The findings are expected to provide basic data for the mechanism research of atmospheric composite particles closer to the real environment. 37178294 5 24 theme isoelectric 1272:1282 arg1 complex 1263:1269 the nano-CaCO3/bacteria complex 1239:1269 the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) 1239:1298 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 5 24 theme isoelectric 1272:1282 arg1 point 1284:1288 isoelectric point pH = 2.0 1272:1297 isoelectric point pH = 2.0 1272:1297 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 1 25 theme aerosol 168:174 arg1 pollution 133:141 the composite pollution 119:141 the composite pollution of atmospheric microbial aerosol 119:174 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 7 26 dep attraction 1694:1703 arg1 force 1726:1730 force 1726:1730 force 1726:1730 The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. 37178294 0 27 theme interfacial 85:95 arg1 interaction 97:107 its interfacial interaction 81:107 its interfacial interaction 81:107 The characteristics of nano-micron calcite particles/common bacteria complex and its interfacial interaction. 37178294 3 28 theme nano-CaCO3 819:828 arg1 bacteria 839:846 single nano-CaCO3 wrapping bacteria 812:846 single nano-CaCO3 wrapping bacteria 812:846 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 6 29 theme surface 1341:1347 arg1 groups 1349:1354 The complex's surface groups 1327:1354 The complex's surface groups 1327:1354 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 8 30 theme β-fold/α-helix 1853:1866 arg1 ratio 1868:1872 the β-fold/α-helix ratio 1849:1872 the β-fold/α-helix ratio of the calcite/S 1849:1889 The increase in the β-fold/α-helix ratio of the calcite/S. 37178294 1 31 theme solution 372:379 arg1 system 381:386 the solution system 368:386 the solution system 368:386 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 4 32 contain has 1051:1053 arg2 agglomeration 1055:1067 agglomeration 1055:1067 agglomeration 1055:1067 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 4 32 contain has 1051:1053 arg1 nano-CaCO3 1040:1049 nano-CaCO3 1040:1049 nano-CaCO3 1040:1049 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 3 33 theme micro-CaCO3 757:767 arg1 edge 749:752 edge 749:752 edge 749:752 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 3 33 theme micro-CaCO3 757:767 arg1 surface 738:744 surface 738:744 surface 738:744 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 4 34 theme particle 988:995 arg1 variation 1002:1010 the nano-CaCO3/bacteria complex's particle size variation 954:1010 the nano-CaCO3/bacteria complex's particle size variation 954:1010 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 2 35 theme modern 490:495 arg1 analysis 497:504 modern analysis and testing methods 490:524 analysis 497:504 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 5 36 theme isoelectric 1141:1151 arg1 complex 1132:1138 the micro-CaCO3/bacteria complex 1107:1138 the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) 1107:1167 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 5 36 theme isoelectric 1141:1151 arg1 point 1153:1157 isoelectric point pH = 3.0 1141:1166 isoelectric point pH = 3.0 1141:1166 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 8 37 theme calcite/S 1881:1889 arg1 ratio 1868:1872 the β-fold/α-helix ratio 1849:1872 the β-fold/α-helix ratio of the calcite/S 1849:1889 The increase in the β-fold/α-helix ratio of the calcite/S. 37178294 7 38 theme electrostatic 1680:1692 arg1 attraction 1694:1703 electrostatic attraction 1680:1703 electrostatic attraction 1680:1703 The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. 37178294 11 39 theme real 2190:2193 arg1 environment 2195:2205 the real environment 2186:2205 the real environment 2186:2205 The findings are expected to provide basic data for the mechanism research of atmospheric composite particles closer to the real environment. 37178294 2 40 theme surface 420:426 arg1 potential 428:436 surface potential 420:436 surface potential 420:436 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 6 41 theme calcite 1412:1418 arg1 particles 1420:1428 calcite particles 1412:1428 calcite particles 1412:1428 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 2 42 theme complex 465:471 arg1 morphology 393:402 The morphology 389:402 The morphology 389:402 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 2 42 theme complex 465:471 arg1 size 414:417 particle size 405:417 particle size 405:417 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 2 42 theme complex 465:471 arg1 potential 428:436 surface potential 420:436 surface potential 420:436 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 2 42 theme complex 465:471 arg1 groups 451:456 surface groups 443:456 surface groups 443:456 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 2 42 theme complex 465:471 arg1 complex 465:471 the complex 461:471 the complex 461:471 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 3 43 theme CLSM 623:626 arg1 results 628:634 The SEM, TEM, and CLSM results 605:634 The SEM, TEM, and CLSM results 605:634 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 1 44 theme bacteria 314:321 arg1 strains 303:309 two common strains 292:309 two common strains of bacteria (Escherichia coli, Staphylococcus aureus) 292:363 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 1 44 theme bacteria 314:321 arg1 particles 278:286 calcite particles 270:286 calcite particles 270:286 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 0 45 theme bacteria 60:67 arg1 complex 69:75 particles/common bacteria complex 43:75 particles/common bacteria complex 43:75 The characteristics of nano-micron calcite particles/common bacteria complex and its interfacial interaction. 37178294 5 46 theme complex 1132:1138 arg1 potential 1094:1102 The surface potential 1082:1102 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) 1082:1167 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 3 47 theme complex 670:676 arg1 morphology 652:661 the morphology 648:661 the morphology of the complex 648:676 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 6 48 theme infrared 1450:1457 arg1 characteristics 1459:1473 the infrared characteristics 1446:1473 the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria 1446:1598 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 11 49 theme composite 2156:2164 arg1 particles 2166:2174 atmospheric composite particles 2144:2174 atmospheric composite particles closer to the real environment 2144:2205 The findings are expected to provide basic data for the mechanism research of atmospheric composite particles closer to the real environment. 37178294 9 50 theme secondary 1926:1934 arg1 stable 1985:1990 stable 1985:1990 stable 1985:1990 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 9 50 theme secondary 1926:1934 arg1 structure 1936:1944 the secondary structure 1922:1944 the secondary structure of bacterial surface proteins 1922:1974 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 1 51 from strains 303:309 arg1 system 381:386 the solution system 368:386 the solution system 368:386 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 9 52 theme surface 1959:1965 arg1 proteins 1967:1974 bacterial surface proteins 1949:1974 bacterial surface proteins 1949:1974 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 11 53 theme closer 2176:2181 arg1 particles 2166:2174 atmospheric composite particles 2144:2174 atmospheric composite particles closer to the real environment 2144:2205 The findings are expected to provide basic data for the mechanism research of atmospheric composite particles closer to the real environment. 37178294 7 54 theme surface 1784:1790 arg1 complexation 1792:1803 surface complexation 1784:1803 surface complexation 1784:1803 The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. 37178294 1 55 from particles 278:286 arg1 system 381:386 the solution system 368:386 the solution system 368:386 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 7 56 theme micro-CaCO3/bacteria 1631:1650 arg1 complex 1652:1658 the micro-CaCO3/bacteria complex 1627:1658 the micro-CaCO3/bacteria complex 1627:1658 The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. 37178294 11 57 theme basic 2103:2107 arg1 data 2109:2112 basic data 2103:2112 basic data for the mechanism research of atmospheric composite particles closer to the real environment 2103:2205 The findings are expected to provide basic data for the mechanism research of atmospheric composite particles closer to the real environment. 37178294 1 58 theme composite 123:131 arg1 pollution 133:141 the composite pollution 119:141 the composite pollution of atmospheric microbial aerosol 119:174 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 7 59 theme interfacial 1605:1615 arg1 action 1617:1622 The interfacial action 1601:1622 The interfacial action of the micro-CaCO3/bacteria complex 1601:1658 The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. 37178294 2 60 theme interfacial 551:561 arg1 interaction 563:573 the interfacial interaction 547:573 the interfacial interaction between calcite and bacteria 547:602 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 9 61 theme bond 2009:2012 arg1 strong 2025:2030 strong 2025:2030 strong 2025:2030 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 9 61 theme bond 2009:2012 arg1 effect 2014:2019 the hydrogen bond effect 1996:2019 the hydrogen bond effect 1996:2019 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 5 62 theme nano-CaCO3/bacteria 1243:1261 arg1 complex 1263:1269 the nano-CaCO3/bacteria complex 1239:1269 the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) 1239:1298 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 5 62 theme nano-CaCO3/bacteria 1243:1261 arg1 point 1284:1288 isoelectric point pH = 2.0 1272:1297 isoelectric point pH = 2.0 1272:1297 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 3 63 theme SEM 609:611 arg1 results 628:634 The SEM, TEM, and CLSM results 605:634 The SEM, TEM, and CLSM results 605:634 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 3 64 theme single 812:817 arg1 bacteria 839:846 single nano-CaCO3 wrapping bacteria 812:846 single nano-CaCO3 wrapping bacteria 812:846 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 10 65 theme coli 2052:2055 arg1 complex 2057:2063 coli complex 2052:2063 coli complex. 2052:2064 coli complex. 37178294 6 66 theme phosphodiester 1566:1579 arg1 bacteria 1591:1598 bacteria 1591:1598 bacteria 1591:1598 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 6 66 theme phosphodiester 1566:1579 arg1 groups 1581:1586 phosphodiester groups 1566:1586 phosphodiester groups of bacteria 1566:1598 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 1 67 theme microbial 158:166 arg1 aerosol 168:174 atmospheric microbial aerosol 146:174 atmospheric microbial aerosol 146:174 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 4 68 theme original 922:929 arg1 particles 939:947 the original mineral particles 918:947 the original mineral particles 918:947 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 5 69 theme surface 1218:1224 arg1 potential 1226:1234 the surface potential 1214:1234 the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) 1214:1298 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 5 70 theme surface 1086:1092 arg1 potential 1094:1102 The surface potential 1082:1102 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) 1082:1167 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 7 71 theme nano-CaCO3/bacteria 1743:1761 arg1 complex 1763:1769 the nano-CaCO3/bacteria complex 1739:1769 the nano-CaCO3/bacteria complex 1739:1769 The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. 37178294 6 72 from protein 1536:1542 arg1 interaction 1515:1525 the interfacial interaction 1499:1525 the interfacial interaction from the protein 1499:1542 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 3 73 theme wrapping 830:837 arg1 bacteria 839:846 single nano-CaCO3 wrapping bacteria 812:846 single nano-CaCO3 wrapping bacteria 812:846 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 2 74 theme testing 510:516 arg1 methods 518:524 modern analysis and testing methods 490:524 methods 518:524 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 6 75 dep based 1361:1365 arg1 accompanied 1431:1441 accompanied 1431:1441 accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria 1431:1598 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 1 76 dep bacteria 314:321 arg1 aureus 357:362 Staphylococcus aureus 342:362 Staphylococcus aureus 342:362 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 1 76 dep bacteria 314:321 arg1 coli 336:339 Escherichia coli 324:339 Escherichia coli 324:339 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 3 77 dep surface 738:744 arg1 the 734:736 the 734:736 the 734:736 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 7 78 theme hydrogen 1709:1716 arg1 bonding 1718:1724 hydrogen bonding 1709:1724 hydrogen bonding 1709:1724 The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. 37178294 0 79 theme nano-micron 23:33 arg1 characteristics 4:18 The characteristics 0:18 The characteristics of nano-micron 0:33 The characteristics of nano-micron calcite particles/common bacteria complex and its interfacial interaction. 37178294 1 80 theme common 296:301 arg1 strains 303:309 two common strains 292:309 two common strains of bacteria (Escherichia coli, Staphylococcus aureus) 292:363 Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. 37178294 4 81 theme size 997:1000 arg1 variation 1002:1010 the nano-CaCO3/bacteria complex's particle size variation 954:1010 the nano-CaCO3/bacteria complex's particle size variation 954:1010 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 0 82 theme particles/common 43:58 arg1 complex 69:75 particles/common bacteria complex 43:75 particles/common bacteria complex 43:75 The characteristics of nano-micron calcite particles/common bacteria complex and its interfacial interaction. 37178294 3 83 theme TEM 614:616 arg1 results 628:634 The SEM, TEM, and CLSM results 605:634 The SEM, TEM, and CLSM results 605:634 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 2 84 theme particle 405:412 arg1 size 414:417 particle size 405:417 particle size 405:417 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 6 85 theme infrared 1384:1391 arg1 characteristics 1393:1407 the infrared characteristics 1380:1407 the infrared characteristics of calcite particles 1380:1428 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 5 86 theme micro-CaCO3/bacteria 1111:1130 arg1 complex 1132:1138 the micro-CaCO3/bacteria complex 1107:1138 the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) 1107:1167 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 5 86 theme micro-CaCO3/bacteria 1111:1130 arg1 point 1153:1157 isoelectric point pH = 3.0 1141:1166 isoelectric point pH = 3.0 1141:1166 The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. 37178294 4 87 theme nano-CaCO3/bacteria 958:976 arg1 complex 978:984 the nano-CaCO3/bacteria complex 954:984 the nano-CaCO3/bacteria complex's particle size variation 954:1010 The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. 37178294 9 88 theme aureus 1892:1897 arg1 complex 1899:1905 aureus complex 1892:1905 aureus complex 1892:1905 aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. 37178294 3 89 dep showed 636:641 arg1 bacteria 770:777 bacteria 770:777 bacteria aggregating with nano-CaCO3 770:805 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 3 89 dep showed 636:641 arg1 bacteria 713:720 bacteria 713:720 bacteria 713:720 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 3 89 dep showed 636:641 arg1 bacteria 839:846 single nano-CaCO3 wrapping bacteria 812:846 single nano-CaCO3 wrapping bacteria 812:846 The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. 37178294 6 90 theme bacteria 1478:1485 arg1 characteristics 1459:1473 the infrared characteristics 1446:1473 the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria 1446:1598 The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. 37178294 2 91 from emphasis 535:542 arg1 interaction 563:573 the interfacial interaction 547:573 the interfacial interaction between calcite and bacteria 547:602 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 2 92 theme surface 443:449 arg1 groups 451:456 surface groups 443:456 surface groups 443:456 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37178294 2 92 theme surface 443:449 arg1 complex 465:471 the complex 461:471 the complex 461:471 The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. 37349387 7 0 theme resonance 866:874 arg1 spectroscopy 876:887 solid-state nuclear magnetic resonance spectroscopy 837:887 solid-state nuclear magnetic resonance spectroscopy 837:887 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 10 1 theme cuticle 1223:1229 arg1 thickness 1231:1239 cuticle thickness 1223:1239 cuticle thickness of insecticide resistant Ae 1223:1267 In contrast, we observed cuticle thickness of insecticide resistant Ae. 37349387 12 2 theme local 1370:1374 arg1 changes 1386:1392 these local cuticular changes 1364:1392 these local cuticular changes 1364:1392 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 12 3 from existence 1477:1485 arg1 vector 1550:1555 this major disease vector 1531:1555 this major disease vector 1531:1555 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 3 4 theme contributing 353:364 arg1 mechanisms 366:375 all contributing mechanisms 349:375 all contributing mechanisms 349:375 To circumvent insecticide resistance, it is essential to understand all contributing mechanisms. 37349387 9 5 from differences 1107:1117 arg1 content 1144:1150 cuticular hydrocarbon content 1122:1150 cuticular hydrocarbon content 1122:1150 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 37349387 9 5 from differences 1107:1117 arg1 deposition 1175:1184 phenolic biopolymer deposition 1155:1184 phenolic biopolymer deposition 1155:1184 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 37349387 7 6 theme susceptible 1079:1089 arg1 Ae 1091:1092 insecticide resistant and susceptible Ae 1053:1092 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1014:1092 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 7 7 dep monooxygenase 1039:1051 arg1 Ae 1091:1092 insecticide resistant and susceptible Ae 1053:1092 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1014:1092 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 7 8 theme insecticide 1053:1063 arg1 Ae 1091:1092 insecticide resistant and susceptible Ae 1053:1092 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1014:1092 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 11 9 theme higher 1312:1317 arg1 abundance 1334:1342 higher polysaccharide abundance 1312:1342 higher polysaccharide abundance 1312:1342 aegypti increased over time and exhibited higher polysaccharide abundance. 37349387 11 10 theme polysaccharide 1319:1332 arg1 abundance 1334:1342 higher polysaccharide abundance 1312:1342 higher polysaccharide abundance 1312:1342 aegypti increased over time and exhibited higher polysaccharide abundance. 37349387 7 11 theme resistant 1065:1073 arg1 Ae 1091:1092 insecticide resistant and susceptible Ae 1053:1092 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1014:1092 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 7 12 theme chromatography/mass 894:912 arg1 spectrometry 914:925 gas chromatography/mass spectrometry 890:925 gas chromatography/mass spectrometry 890:925 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 2 13 dep health 180:185 arg1 concerns 187:194 concerns 187:194 concerns 187:194 Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. 37349387 12 14 from differences 1427:1437 arg1 mosquito 1452:1459 the whole mosquito 1442:1459 the whole mosquito 1442:1459 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 5 15 theme cuticular 686:694 arg1 resistance 696:705 cuticular resistance 686:705 cuticular resistance 686:705 Cuticle interface alterations can slow or prevent insecticide penetration in a phenomenon referred to as cuticular resistance. 37349387 1 16 theme made 78:81 arg1 strides 89:95 made great strides 78:95 made great strides 78:95 Insecticides have made great strides in reducing the global burden of vector-borne disease. 37349387 9 17 theme phenolic 1155:1162 arg1 deposition 1175:1184 phenolic biopolymer deposition 1155:1184 phenolic biopolymer deposition 1155:1184 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 37349387 12 18 theme whole 1446:1450 arg1 mosquito 1452:1459 the whole mosquito 1442:1459 the whole mosquito 1442:1459 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 9 19 theme hydrocarbon 1132:1142 arg1 content 1144:1150 cuticular hydrocarbon content 1122:1150 cuticular hydrocarbon content 1122:1150 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 37349387 4 20 theme phenolic 537:544 arg1 sclerotin 558:566 sclerotin 558:566 sclerotin 558:566 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 37349387 4 20 theme phenolic 537:544 arg1 biopolymers 546:556 phenolic biopolymers 537:556 phenolic biopolymers sclerotin and melanin 537:578 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 37349387 4 20 theme phenolic 537:544 arg1 melanin 572:578 melanin 572:578 melanin 572:578 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 37349387 5 21 theme insecticide 631:641 arg1 penetration 643:653 insecticide penetration 631:653 insecticide penetration 631:653 Cuticle interface alterations can slow or prevent insecticide penetration in a phenomenon referred to as cuticular resistance. 37349387 1 22 theme great 83:87 arg1 strides 89:95 made great strides 78:95 made great strides 78:95 Insecticides have made great strides in reducing the global burden of vector-borne disease. 37349387 7 23 theme transmission 932:943 arg1 microscopy 954:963 transmission electron microscopy 932:963 transmission electron microscopy 932:963 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 7 24 theme P450 1034:1037 arg1 monooxygenase 1039:1051 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1014:1092 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1014:1092 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 7 25 theme electron 945:952 arg1 microscopy 954:963 transmission electron microscopy 932:963 transmission electron microscopy 932:963 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 7 26 theme monooxygenase 1039:1051 arg1 composition 999:1009 the cuticle composition 987:1009 the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 987:1092 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 0 27 theme Cuticular 0:8 arg1 profiling 10:18 Cuticular profiling 0:18 Cuticular profiling of insecticide resistant Aedes aegypti. 0:58 Cuticular profiling of insecticide resistant Aedes aegypti. 37349387 7 28 theme cytochrome 1023:1032 arg1 monooxygenase 1039:1051 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1014:1092 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1014:1092 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 0 29 theme insecticide 23:33 arg1 aegypti 51:57 insecticide resistant Aedes aegypti 23:57 insecticide resistant Aedes aegypti 23:57 Cuticular profiling of insecticide resistant Aedes aegypti. 37349387 7 30 theme gas 890:892 arg1 spectrometry 914:925 gas chromatography/mass spectrometry 890:925 gas chromatography/mass spectrometry 890:925 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 4 31 theme insect 430:435 arg1 cuticle 437:443 the insect cuticle 426:443 the insect cuticle 426:443 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 37349387 12 32 theme disease 1542:1548 arg1 vector 1550:1555 this major disease vector 1531:1555 this major disease vector 1531:1555 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 6 33 theme mosquito 766:773 arg1 characterization 729:744 Cuticular resistance characterization 708:744 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti, 708:789 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti, is lacking. 37349387 12 34 theme metabolic 1417:1425 arg1 differences 1427:1437 global metabolic differences 1410:1437 global metabolic differences in the whole mosquito 1410:1459 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 1 35 contain have 73:76 arg1 Insecticides 60:71 Insecticides 60:71 Insecticides 60:71 Insecticides have made great strides in reducing the global burden of vector-borne disease. 37349387 1 35 contain have 73:76 arg2 strides 89:95 made great strides 78:95 made great strides 78:95 Insecticides have made great strides in reducing the global burden of vector-borne disease. 37349387 4 36 theme cuticular 499:507 arg1 proteins 509:516 cuticular proteins 499:516 cuticular proteins 499:516 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 37349387 12 37 theme major 1536:1540 arg1 vector 1550:1555 this major disease vector 1531:1555 this major disease vector 1531:1555 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 6 38 theme fever 760:764 arg1 mosquito 766:773 the yellow fever mosquito 749:773 the yellow fever mosquito 749:773 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti, is lacking. 37349387 6 38 theme fever 760:764 arg1 aegypti 782:788 Aedes aegypti 776:788 Aedes aegypti 776:788 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti, is lacking. 37349387 12 39 theme global 1410:1415 arg1 differences 1427:1437 global metabolic differences 1410:1437 global metabolic differences in the whole mosquito 1410:1459 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 0 40 theme Aedes 45:49 arg1 aegypti 51:57 insecticide resistant Aedes aegypti 23:57 insecticide resistant Aedes aegypti 23:57 Cuticular profiling of insecticide resistant Aedes aegypti. 37349387 10 41 theme insecticide 1244:1254 arg1 Ae 1266:1267 insecticide resistant Ae 1244:1267 insecticide resistant Ae 1244:1267 In contrast, we observed cuticle thickness of insecticide resistant Ae. 37349387 3 42 theme insecticide 295:305 arg1 resistance 307:316 insecticide resistance 295:316 insecticide resistance 295:316 To circumvent insecticide resistance, it is essential to understand all contributing mechanisms. 37349387 12 43 theme cuticular 1496:1504 arg1 mechanisms 1517:1526 novel cuticular resistance mechanisms 1490:1526 novel cuticular resistance mechanisms 1490:1526 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 6 44 theme yellow 753:758 arg1 mosquito 766:773 the yellow fever mosquito 749:773 the yellow fever mosquito 749:773 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti, is lacking. 37349387 6 44 theme yellow 753:758 arg1 aegypti 782:788 Aedes aegypti 776:788 Aedes aegypti 776:788 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti, is lacking. 37349387 0 45 theme resistant 35:43 arg1 aegypti 51:57 insecticide resistant Aedes aegypti 23:57 insecticide resistant Aedes aegypti 23:57 Cuticular profiling of insecticide resistant Aedes aegypti. 37349387 7 46 theme nuclear 849:855 arg1 resonance 866:874 nuclear magnetic resonance 849:874 solid-state nuclear magnetic resonance spectroscopy 837:887 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 2 47 theme public 173:178 arg1 health 180:185 serious public health 165:185 serious public health concerns 165:194 Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. 37349387 10 48 theme Ae 1266:1267 arg1 thickness 1231:1239 cuticle thickness 1223:1239 cuticle thickness of insecticide resistant Ae 1223:1267 In contrast, we observed cuticle thickness of insecticide resistant Ae. 37349387 12 49 theme resistance 1506:1515 arg1 mechanisms 1517:1526 novel cuticular resistance mechanisms 1490:1526 novel cuticular resistance mechanisms 1490:1526 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 7 50 theme solid-state 837:847 arg1 spectroscopy 876:887 solid-state nuclear magnetic resonance spectroscopy 837:887 solid-state nuclear magnetic resonance spectroscopy 837:887 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 9 51 theme cuticular 1122:1130 arg1 content 1144:1150 cuticular hydrocarbon content 1122:1150 cuticular hydrocarbon content 1122:1150 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 37349387 7 52 theme magnetic 857:864 arg1 resonance 866:874 nuclear magnetic resonance 849:874 solid-state nuclear magnetic resonance spectroscopy 837:887 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 2 53 theme serious 165:171 arg1 health 180:185 serious public health 165:185 serious public health concerns 165:194 Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. 37349387 12 54 theme mechanisms 1517:1526 arg1 existence 1477:1485 the existence 1473:1485 the existence of novel cuticular resistance mechanisms in this major disease vector 1473:1555 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 4 55 theme Contact-based 378:390 arg1 insecticides 392:403 Contact-based insecticides 378:403 Contact-based insecticides 378:403 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 37349387 1 56 theme global 113:118 arg1 burden 120:125 the global burden 109:125 the global burden of vector-borne disease 109:149 Insecticides have made great strides in reducing the global burden of vector-borne disease. 37349387 0 57 theme aegypti 51:57 arg1 profiling 10:18 Cuticular profiling 0:18 Cuticular profiling of insecticide resistant Aedes aegypti. 0:58 Cuticular profiling of insecticide resistant Aedes aegypti. 37349387 2 58 theme vector 233:238 arg1 populations 240:250 insecticide-resistant vector populations 211:250 insecticide-resistant vector populations 211:250 Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. 37349387 7 59 used utilized 828:835 arg2 we 825:826 we 825:826 we 825:826 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 12 60 theme cuticular 1376:1384 arg1 changes 1386:1392 these local cuticular changes 1364:1392 these local cuticular changes 1364:1392 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 4 61 dep biopolymers 546:556 arg1 sclerotin 558:566 sclerotin 558:566 sclerotin 558:566 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 37349387 4 61 dep biopolymers 546:556 arg1 biopolymers 546:556 phenolic biopolymers 537:556 phenolic biopolymers sclerotin and melanin 537:578 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 37349387 4 61 dep biopolymers 546:556 arg1 melanin 572:578 melanin 572:578 melanin 572:578 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 37349387 2 62 theme insecticide-resistant 211:231 arg1 populations 240:250 insecticide-resistant vector populations 211:250 insecticide-resistant vector populations 211:250 Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. 37349387 12 63 theme novel 1490:1494 arg1 mechanisms 1517:1526 novel cuticular resistance mechanisms 1490:1526 novel cuticular resistance mechanisms 1490:1526 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 37349387 7 64 theme congenic 1014:1021 arg1 monooxygenase 1039:1051 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1014:1092 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1014:1092 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 10 65 theme resistant 1256:1264 arg1 Ae 1266:1267 insecticide resistant Ae 1244:1267 insecticide resistant Ae 1244:1267 In contrast, we observed cuticle thickness of insecticide resistant Ae. 37349387 1 66 theme vector-borne 130:141 arg1 disease 143:149 vector-borne disease 130:149 vector-borne disease 130:149 Insecticides have made great strides in reducing the global burden of vector-borne disease. 37349387 7 67 theme cuticle 991:997 arg1 composition 999:1009 the cuticle composition 987:1009 the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 987:1092 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 4 68 theme chitin 475:480 arg1 polysaccharides 482:496 chitin polysaccharides 475:496 chitin polysaccharides 475:496 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 37349387 5 69 theme Cuticle 581:587 arg1 alterations 599:609 Cuticle interface alterations 581:609 Cuticle interface alterations 581:609 Cuticle interface alterations can slow or prevent insecticide penetration in a phenomenon referred to as cuticular resistance. 37349387 1 70 theme disease 143:149 arg1 burden 120:125 the global burden 109:125 the global burden of vector-borne disease 109:149 Insecticides have made great strides in reducing the global burden of vector-borne disease. 37349387 6 71 theme resistance 718:727 arg1 characterization 729:744 Cuticular resistance characterization 708:744 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti, 708:789 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti, is lacking. 37349387 7 72 theme current 810:816 arg1 study 818:822 the current study 806:822 the current study 806:822 In the current study, we utilized solid-state nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and transmission electron microscopy to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 37349387 9 73 theme biopolymer 1164:1173 arg1 deposition 1175:1184 phenolic biopolymer deposition 1155:1184 phenolic biopolymer deposition 1155:1184 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 37349387 5 74 theme interface 589:597 arg1 alterations 599:609 Cuticle interface alterations 581:609 Cuticle interface alterations 581:609 Cuticle interface alterations can slow or prevent insecticide penetration in a phenomenon referred to as cuticular resistance. 37349387 6 75 theme Cuticular 708:716 arg1 characterization 729:744 Cuticular resistance characterization 708:744 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti, 708:789 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti, is lacking. 36712033 7 0 theme Resonance 867:875 arg1 spectroscopy 885:896 solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy 838:896 solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy 838:896 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 7 1 theme cytochrome 1046:1055 arg1 monooxygenase 1062:1074 congenic cytochrome P450 monooxygenase 1037:1074 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1037:1115 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 12 2 theme resistance 1530:1539 arg1 mechanisms 1541:1550 novel cuticular resistance mechanisms 1514:1550 novel cuticular resistance mechanisms 1514:1550 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 7 3 theme electron 962:969 arg1 TEM 983:985 TEM 983:985 TEM 983:985 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 7 3 theme electron 962:969 arg1 microscopy 971:980 transmission electron microscopy 949:980 transmission electron microscopy (TEM) 949:986 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 12 4 from existence 1501:1509 arg1 vector 1574:1579 this major disease vector 1555:1579 this major disease vector 1555:1579 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 3 5 theme contributing 353:364 arg1 mechanisms 366:375 all contributing mechanisms 349:375 all contributing mechanisms 349:375 To circumvent insecticide resistance, it is essential to understand all contributing mechanisms. 36712033 12 6 from differences 1451:1461 arg1 mosquito 1476:1483 the whole mosquito 1466:1483 the whole mosquito 1466:1483 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 12 7 theme novel 1514:1518 arg1 mechanisms 1541:1550 novel cuticular resistance mechanisms 1514:1550 novel cuticular resistance mechanisms 1514:1550 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 9 8 theme cuticular 1146:1154 arg1 content 1168:1174 cuticular hydrocarbon content 1146:1174 cuticular hydrocarbon content 1146:1174 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 36712033 7 9 theme susceptible 1102:1112 arg1 Ae 1114:1115 insecticide resistant and susceptible Ae 1076:1115 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1037:1115 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 9 10 theme hydrocarbon 1156:1166 arg1 content 1168:1174 cuticular hydrocarbon content 1146:1174 cuticular hydrocarbon content 1146:1174 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 36712033 2 11 dep health 180:185 arg1 concerns 187:194 concerns 187:194 concerns 187:194 Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. 36712033 12 12 theme mechanisms 1541:1550 arg1 existence 1501:1509 the existence 1497:1509 the existence of novel cuticular resistance mechanisms in this major disease vector 1497:1579 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 5 13 theme cuticular 686:694 arg1 resistance 696:705 cuticular resistance 686:705 cuticular resistance 686:705 Cuticle interface alterations can slow or prevent insecticide penetration in a phenomenon referred to as cuticular resistance. 36712033 7 14 theme cuticle 1014:1020 arg1 composition 1022:1032 the cuticle composition 1010:1032 the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1010:1115 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 1 15 theme made 78:81 arg1 strides 89:95 made great strides 78:95 made great strides 78:95 Insecticides have made great strides in reducing the global burden of vector-borne disease. 36712033 12 16 theme cuticular 1400:1408 arg1 changes 1410:1416 these local cuticular changes 1388:1416 these local cuticular changes 1388:1416 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 4 17 theme phenolic 537:544 arg1 sclerotin 558:566 sclerotin 558:566 sclerotin 558:566 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 36712033 4 17 theme phenolic 537:544 arg1 biopolymers 546:556 phenolic biopolymers 537:556 phenolic biopolymers sclerotin and melanin 537:578 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 36712033 4 17 theme phenolic 537:544 arg1 melanin 572:578 melanin 572:578 melanin 572:578 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 36712033 5 18 theme insecticide 631:641 arg1 penetration 643:653 insecticide penetration 631:653 insecticide penetration 631:653 Cuticle interface alterations can slow or prevent insecticide penetration in a phenomenon referred to as cuticular resistance. 36712033 1 19 theme great 83:87 arg1 strides 89:95 made great strides 78:95 made great strides 78:95 Insecticides have made great strides in reducing the global burden of vector-borne disease. 36712033 12 20 theme local 1394:1398 arg1 changes 1410:1416 these local cuticular changes 1388:1416 these local cuticular changes 1388:1416 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 9 21 theme phenolic 1179:1186 arg1 deposition 1199:1208 phenolic biopolymer deposition 1179:1208 phenolic biopolymer deposition 1179:1208 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 36712033 12 22 theme cuticular 1520:1528 arg1 mechanisms 1541:1550 novel cuticular resistance mechanisms 1514:1550 novel cuticular resistance mechanisms 1514:1550 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 0 23 theme Cuticular 0:8 arg1 profiling 10:18 Cuticular profiling 0:18 Cuticular profiling of insecticide resistant Aedes aegypti. 0:58 Cuticular profiling of insecticide resistant Aedes aegypti. 36712033 12 24 theme disease 1566:1572 arg1 vector 1574:1579 this major disease vector 1555:1579 this major disease vector 1555:1579 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 7 25 theme gas 899:901 arg1 GC-MS 937:941 GC-MS 937:941 GC-MS 937:941 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 7 25 theme gas 899:901 arg1 spectrometry 923:934 gas chromatography/mass spectrometry 899:934 gas chromatography/mass spectrometry (GC-MS) 899:942 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 12 26 theme major 1560:1564 arg1 vector 1574:1579 this major disease vector 1555:1579 this major disease vector 1555:1579 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 0 27 theme insecticide 23:33 arg1 aegypti 51:57 insecticide resistant Aedes aegypti 23:57 insecticide resistant Aedes aegypti 23:57 Cuticular profiling of insecticide resistant Aedes aegypti. 36712033 10 28 theme cuticle 1247:1253 arg1 thickness 1255:1263 cuticle thickness 1247:1263 cuticle thickness of insecticide resistant Ae 1247:1291 In contrast, we observed cuticle thickness of insecticide resistant Ae. 36712033 4 29 theme insect 430:435 arg1 cuticle 437:443 the insect cuticle 426:443 the insect cuticle 426:443 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 36712033 6 30 theme mosquito 766:773 arg1 characterization 729:744 Cuticular resistance characterization 708:744 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , 708:790 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , is lacking. 36712033 7 31 theme monooxygenase 1062:1074 arg1 composition 1022:1032 the cuticle composition 1010:1032 the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1010:1115 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 1 32 contain have 73:76 arg1 Insecticides 60:71 Insecticides 60:71 Insecticides 60:71 Insecticides have made great strides in reducing the global burden of vector-borne disease. 36712033 1 32 contain have 73:76 arg2 strides 89:95 made great strides 78:95 made great strides 78:95 Insecticides have made great strides in reducing the global burden of vector-borne disease. 36712033 7 33 theme congenic 1037:1044 arg1 monooxygenase 1062:1074 congenic cytochrome P450 monooxygenase 1037:1074 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1037:1115 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 4 34 theme cuticular 499:507 arg1 proteins 509:516 cuticular proteins 499:516 cuticular proteins 499:516 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 36712033 7 35 dep monooxygenase 1062:1074 arg1 Ae 1114:1115 insecticide resistant and susceptible Ae 1076:1115 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1037:1115 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 6 36 theme fever 760:764 arg1 mosquito 766:773 the yellow fever mosquito 749:773 the yellow fever mosquito 749:773 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , is lacking. 36712033 6 36 theme fever 760:764 arg1 aegypti 782:788 Aedes aegypti 776:788 Aedes aegypti 776:788 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , is lacking. 36712033 9 37 theme biopolymer 1188:1197 arg1 deposition 1199:1208 phenolic biopolymer deposition 1179:1208 phenolic biopolymer deposition 1179:1208 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 36712033 0 38 theme Aedes 45:49 arg1 aegypti 51:57 insecticide resistant Aedes aegypti 23:57 insecticide resistant Aedes aegypti 23:57 Cuticular profiling of insecticide resistant Aedes aegypti. 36712033 3 39 theme insecticide 295:305 arg1 resistance 307:316 insecticide resistance 295:316 insecticide resistance 295:316 To circumvent insecticide resistance, it is essential to understand all contributing mechanisms. 36712033 6 40 theme yellow 753:758 arg1 mosquito 766:773 the yellow fever mosquito 749:773 the yellow fever mosquito 749:773 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , is lacking. 36712033 6 40 theme yellow 753:758 arg1 aegypti 782:788 Aedes aegypti 776:788 Aedes aegypti 776:788 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , is lacking. 36712033 0 41 theme resistant 35:43 arg1 aegypti 51:57 insecticide resistant Aedes aegypti 23:57 insecticide resistant Aedes aegypti 23:57 Cuticular profiling of insecticide resistant Aedes aegypti. 36712033 7 42 theme Nuclear 850:856 arg1 ssNMR 878:882 ssNMR 878:882 ssNMR 878:882 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 7 42 theme Nuclear 850:856 arg1 Resonance 867:875 Nuclear Magnetic Resonance 850:875 solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy 838:896 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 2 43 theme public 173:178 arg1 health 180:185 serious public health 165:185 serious public health concerns 165:194 Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. 36712033 10 44 theme insecticide 1268:1278 arg1 Ae 1290:1291 insecticide resistant Ae 1268:1291 insecticide resistant Ae 1268:1291 In contrast, we observed cuticle thickness of insecticide resistant Ae. 36712033 12 45 theme whole 1470:1474 arg1 mosquito 1476:1483 the whole mosquito 1466:1483 the whole mosquito 1466:1483 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 7 46 theme solid-state 838:848 arg1 spectroscopy 885:896 solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy 838:896 solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy 838:896 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 7 47 theme chromatography/mass 903:921 arg1 GC-MS 937:941 GC-MS 937:941 GC-MS 937:941 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 7 47 theme chromatography/mass 903:921 arg1 spectrometry 923:934 gas chromatography/mass spectrometry 899:934 gas chromatography/mass spectrometry (GC-MS) 899:942 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 2 48 theme serious 165:171 arg1 health 180:185 serious public health 165:185 serious public health concerns 165:194 Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. 36712033 4 49 theme Contact-based 378:390 arg1 insecticides 392:403 Contact-based insecticides 378:403 Contact-based insecticides 378:403 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 36712033 1 50 theme global 113:118 arg1 burden 120:125 the global burden 109:125 the global burden of vector-borne disease 109:149 Insecticides have made great strides in reducing the global burden of vector-borne disease. 36712033 0 51 theme aegypti 51:57 arg1 profiling 10:18 Cuticular profiling 0:18 Cuticular profiling of insecticide resistant Aedes aegypti. 0:58 Cuticular profiling of insecticide resistant Aedes aegypti. 36712033 2 52 theme vector 233:238 arg1 populations 240:250 insecticide-resistant vector populations 211:250 insecticide-resistant vector populations 211:250 Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. 36712033 7 53 used utilized 829:836 arg2 we 826:827 we 826:827 we 826:827 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 11 54 theme higher 1336:1341 arg1 abundance 1358:1366 higher polysaccharide abundance 1336:1366 higher polysaccharide abundance 1336:1366 aegypti increased over time and exhibited higher polysaccharide abundance. 36712033 4 55 dep biopolymers 546:556 arg1 sclerotin 558:566 sclerotin 558:566 sclerotin 558:566 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 36712033 4 55 dep biopolymers 546:556 arg1 biopolymers 546:556 phenolic biopolymers 537:556 phenolic biopolymers sclerotin and melanin 537:578 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 36712033 4 55 dep biopolymers 546:556 arg1 melanin 572:578 melanin 572:578 melanin 572:578 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 36712033 11 56 theme polysaccharide 1343:1356 arg1 abundance 1358:1366 higher polysaccharide abundance 1336:1366 higher polysaccharide abundance 1336:1366 aegypti increased over time and exhibited higher polysaccharide abundance. 36712033 2 57 theme insecticide-resistant 211:231 arg1 populations 240:250 insecticide-resistant vector populations 211:250 insecticide-resistant vector populations 211:250 Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. 36712033 12 58 theme global 1434:1439 arg1 differences 1451:1461 global metabolic differences 1434:1461 global metabolic differences in the whole mosquito 1434:1483 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 7 59 theme resistant 1088:1096 arg1 Ae 1114:1115 insecticide resistant and susceptible Ae 1076:1115 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1037:1115 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 7 60 theme transmission 949:960 arg1 TEM 983:985 TEM 983:985 TEM 983:985 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 7 60 theme transmission 949:960 arg1 microscopy 971:980 transmission electron microscopy 949:980 transmission electron microscopy (TEM) 949:986 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 10 61 theme Ae 1290:1291 arg1 thickness 1255:1263 cuticle thickness 1247:1263 cuticle thickness of insecticide resistant Ae 1247:1291 In contrast, we observed cuticle thickness of insecticide resistant Ae. 36712033 9 62 from differences 1131:1141 arg1 deposition 1199:1208 phenolic biopolymer deposition 1179:1208 phenolic biopolymer deposition 1179:1208 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 36712033 9 62 from differences 1131:1141 arg1 content 1168:1174 cuticular hydrocarbon content 1146:1174 cuticular hydrocarbon content 1146:1174 No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. 36712033 7 63 theme P450 1057:1060 arg1 monooxygenase 1062:1074 congenic cytochrome P450 monooxygenase 1037:1074 congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae 1037:1115 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 1 64 theme vector-borne 130:141 arg1 disease 143:149 vector-borne disease 130:149 vector-borne disease 130:149 Insecticides have made great strides in reducing the global burden of vector-borne disease. 36712033 10 65 theme resistant 1280:1288 arg1 Ae 1290:1291 insecticide resistant Ae 1268:1291 insecticide resistant Ae 1268:1291 In contrast, we observed cuticle thickness of insecticide resistant Ae. 36712033 4 66 theme chitin 475:480 arg1 polysaccharides 482:496 chitin polysaccharides 475:496 chitin polysaccharides 475:496 Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. 36712033 5 67 theme Cuticle 581:587 arg1 alterations 599:609 Cuticle interface alterations 581:609 Cuticle interface alterations 581:609 Cuticle interface alterations can slow or prevent insecticide penetration in a phenomenon referred to as cuticular resistance. 36712033 1 68 theme disease 143:149 arg1 burden 120:125 the global burden 109:125 the global burden of vector-borne disease 109:149 Insecticides have made great strides in reducing the global burden of vector-borne disease. 36712033 6 69 theme resistance 718:727 arg1 characterization 729:744 Cuticular resistance characterization 708:744 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , 708:790 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , is lacking. 36712033 7 70 theme current 811:817 arg1 study 819:823 the current study 807:823 the current study 807:823 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 12 71 theme metabolic 1441:1449 arg1 differences 1451:1461 global metabolic differences 1434:1461 global metabolic differences in the whole mosquito 1434:1483 Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector. 36712033 5 72 theme interface 589:597 arg1 alterations 599:609 Cuticle interface alterations 581:609 Cuticle interface alterations 581:609 Cuticle interface alterations can slow or prevent insecticide penetration in a phenomenon referred to as cuticular resistance. 36712033 6 73 theme Cuticular 708:716 arg1 characterization 729:744 Cuticular resistance characterization 708:744 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , 708:790 Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , is lacking. 36712033 7 74 theme Magnetic 858:865 arg1 ssNMR 878:882 ssNMR 878:882 ssNMR 878:882 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 36712033 7 74 theme Magnetic 858:865 arg1 Resonance 867:875 Nuclear Magnetic Resonance 850:875 solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy 838:896 In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. 35307476 6 0 theme viability 893:901 arg1 qPCR 953:956 qPCR 953:956 qPCR 953:956 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 6 0 theme viability 893:901 arg1 reaction 943:950 viability real-time quantitative polymerase chain reaction 893:950 viability real-time quantitative polymerase chain reaction (qPCR) 893:957 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 12 1 dep CONCLUSION 1696:1705 arg1 enhances 1747:1754 enhances 1747:1754 enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v 1747:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 2 2 theme 5 287:287 arg1 % 288:288 % 288:288 % 288:288 METHODS Experimental varnishes were prepared by incorporating L-Arg (1, 2, and 4%) in 5% NaF varnish, which served as the control. 35307476 12 3 theme F. 1829:1830 arg1 SIGNIFICANCE 1841:1852 released Arg and F. CLINICAL SIGNIFICANCE 1812:1852 released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v 1812:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 6 4 from composition 850:860 arg1 biofilms 865:872 biofilms 865:872 biofilms 865:872 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 8 5 theme biofilm 1100:1106 arg1 thickness 1108:1116 biofilm thickness 1100:1116 biofilm thickness 1100:1116 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 12 6 theme % 1790:1790 arg1 varnish 1796:1802 5% NaF varnish 1789:1802 5% NaF varnish 1789:1802 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 4 7 theme biofilm 614:620 arg1 composition 622:632 biofilm composition 614:632 biofilm composition 614:632 The HA discs with treated biofilms were examined for biofilm composition. 35307476 10 8 theme SMU.150 1484:1490 arg1 Expression 1464:1473 Expression 1464:1473 Expression of gtfB, SMU.150, and nlmD 1464:1500 Expression of gtfB, SMU.150, and nlmD were significantly downregulated in 4% Arg-NaF-treated biofilms; while 2% Arg-NaF enhanced the expression of arcA. 35307476 9 9 theme % 1341:1341 arg1 biofilms 1359:1366 the 4% Arg-NaF-treated biofilms 1336:1366 the 4% Arg-NaF-treated biofilms 1336:1366 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 12 10 theme Arg 1821:1823 arg1 SIGNIFICANCE 1841:1852 released Arg and F. CLINICAL SIGNIFICANCE 1812:1852 released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v 1812:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 3 11 theme experimental 528:539 arg1 groups 553:558 the experimental and control groups 524:558 groups 553:558 Multi-species biofilms comprising Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii were grown on hydroxyapatite (HA) discs and treated with the Arg and F released from the experimental and control groups. 35307476 10 12 theme gtfB 1478:1481 arg1 Expression 1464:1473 Expression 1464:1473 Expression of gtfB, SMU.150, and nlmD 1464:1500 Expression of gtfB, SMU.150, and nlmD were significantly downregulated in 4% Arg-NaF-treated biofilms; while 2% Arg-NaF enhanced the expression of arcA. 35307476 8 13 theme % 1129:1129 arg1 group 1139:1143 the 4% Arg-NaF group 1124:1143 the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria 1124:1203 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 8 14 theme bacteria 1196:1203 arg1 proportion 1177:1186 a significantly greater proportion 1153:1186 a significantly greater proportion of dead bacteria 1153:1203 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 11 15 theme sagP 1690:1693 arg1 expression 1676:1685 the expression 1672:1685 the expression of sagP 1672:1693 Both 2% Arg-NaF and 4% Arg-NaF significantly increased the expression of sagP. 35307476 3 16 theme control 545:551 arg1 groups 553:558 the experimental and control groups 524:558 groups 553:558 Multi-species biofilms comprising Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii were grown on hydroxyapatite (HA) discs and treated with the Arg and F released from the experimental and control groups. 35307476 9 17 theme higher 1381:1386 arg1 concentration 1388:1400 higher concentration 1381:1400 higher concentration of eDNA and proteins 1381:1421 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 12 18 theme NaF 1792:1794 arg1 varnish 1796:1802 5% NaF varnish 1789:1802 5% NaF varnish 1789:1802 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 6 19 theme chain 937:941 arg1 qPCR 953:956 qPCR 953:956 qPCR 953:956 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 6 19 theme chain 937:941 arg1 reaction 943:950 viability real-time quantitative polymerase chain reaction 893:950 viability real-time quantitative polymerase chain reaction (qPCR) 893:957 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 2 20 theme Experimental 209:220 arg1 varnishes 222:230 METHODS Experimental varnishes 201:230 METHODS Experimental varnishes 201:230 METHODS Experimental varnishes were prepared by incorporating L-Arg (1, 2, and 4%) in 5% NaF varnish, which served as the control. 35307476 6 21 theme quantitative 913:924 arg1 qPCR 953:956 qPCR 953:956 qPCR 953:956 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 6 21 theme quantitative 913:924 arg1 reaction 943:950 viability real-time quantitative polymerase chain reaction 893:950 viability real-time quantitative polymerase chain reaction (qPCR) 893:957 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 12 22 theme /4 1906:1907 arg1 w/v 1910:1912 at 2%/4% w/v 1901:1912 at 2%/4% w/v 1901:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 11 23 theme 2 1622:1622 arg1 % 1623:1623 % 1623:1623 % 1623:1623 Both 2% Arg-NaF and 4% Arg-NaF significantly increased the expression of sagP. 35307476 5 24 theme biofilm 639:645 arg1 thickness 647:655 The biofilm thickness and live/dead counts 635:676 thickness 647:655 The biofilm thickness and live/dead counts were investigated using confocal microscopic imaging, while biofilm polysaccharides, proteins, and extracellular DNA (eDNA) were assessed spectrophotometrically. 35307476 7 25 theme gene 973:976 arg1 RGE 990:992 RGE 990:992 RGE 990:992 The relative gene expression (RGE) was determined for gtfB, SMU.150, nlmD, arcA, and sagP. 35307476 7 25 theme gene 973:976 arg1 expression 978:987 The relative gene expression 960:987 The relative gene expression (RGE) 960:993 The relative gene expression (RGE) was determined for gtfB, SMU.150, nlmD, arcA, and sagP. 35307476 3 26 dep Arg 500:502 arg1 the 496:498 the 496:498 the 496:498 Multi-species biofilms comprising Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii were grown on hydroxyapatite (HA) discs and treated with the Arg and F released from the experimental and control groups. 35307476 8 27 theme 1 1218:1218 arg1 p < 0.001 1236:1244 p < 0.001 1236:1244 p < 0.001 1236:1244 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 8 27 theme 1 1218:1218 arg1 Arg-NaF 1227:1233 1 and 2% Arg-NaF 1218:1233 Arg-NaF 1227:1233 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 8 28 theme 2 1224:1224 arg1 p < 0.001 1236:1244 p < 0.001 1236:1244 p < 0.001 1236:1244 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 8 28 theme 2 1224:1224 arg1 Arg-NaF 1227:1233 1 and 2% Arg-NaF 1218:1233 Arg-NaF 1227:1233 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 13 29 theme cariogenic 1950:1959 arg1 biofilms 1961:1968 cariogenic biofilms 1950:1968 cariogenic biofilms 1950:1968 Arg) has the potential to modulate cariogenic biofilms in high-risk individuals. 35307476 11 30 theme 4 1637:1637 arg1 % 1638:1638 % 1638:1638 % 1638:1638 Both 2% Arg-NaF and 4% Arg-NaF significantly increased the expression of sagP. 35307476 8 31 dep groups 1085:1090 arg1 % 1075:1075 % 1075:1075 % 1075:1075 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 12 32 theme modulatory 1768:1777 arg1 effect 1779:1784 the biofilm modulatory effect 1756:1784 the biofilm modulatory effect of 5% NaF varnish 1756:1802 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 12 33 dep varnish 1892:1898 arg1 w/v 1910:1912 at 2%/4% w/v 1901:1912 at 2%/4% w/v 1901:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 8 34 dep % 1075:1075 arg1 4 1074:1074 4 1074:1074 4 1074:1074 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 8 34 dep % 1075:1075 arg1 2 1068:1068 2 1068:1068 2 1068:1068 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 10 35 theme % 1539:1539 arg1 biofilms 1557:1564 4% Arg-NaF-treated biofilms 1538:1564 4% Arg-NaF-treated biofilms 1538:1564 Expression of gtfB, SMU.150, and nlmD were significantly downregulated in 4% Arg-NaF-treated biofilms; while 2% Arg-NaF enhanced the expression of arcA. 35307476 5 36 theme confocal 702:709 arg1 imaging 723:729 confocal microscopic imaging 702:729 confocal microscopic imaging 702:729 The biofilm thickness and live/dead counts were investigated using confocal microscopic imaging, while biofilm polysaccharides, proteins, and extracellular DNA (eDNA) were assessed spectrophotometrically. 35307476 13 37 contain has 1920:1922 arg2 potential 1928:1936 the potential to modulate cariogenic biofilms in high-risk individuals 1924:1993 the potential to modulate cariogenic biofilms in high-risk individuals 1924:1993 Arg) has the potential to modulate cariogenic biofilms in high-risk individuals. 35307476 13 37 contain has 1920:1922 arg1 Arg 1915:1917 Arg) 1915:1918 Arg) 1915:1918 Arg) has the potential to modulate cariogenic biofilms in high-risk individuals. 35307476 1 38 dep -fluoride 152:160 arg1 F 163:163 F 163:163 F 163:163 OBJECTIVES To examine the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms. 35307476 0 39 theme Biofilm 0:6 arg1 response 19:26 Biofilm modulatory response 0:26 Biofilm modulatory response of arginine-fluoride 0:47 Biofilm modulatory response of arginine-fluoride varnish on multi-species biofilm. 35307476 1 40 from effect 128:133 arg1 biofilms 191:198 multi-species biofilms 177:198 multi-species biofilms 177:198 OBJECTIVES To examine the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms. 35307476 12 41 dep SIGNIFICANCE 1841:1852 arg1 indicate 1872:1879 indicate 1872:1879 indicate that Arg-F varnish (at 2%/4% w/v 1872:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 12 42 theme L-arginine 1728:1737 arg1 incorporation 1711:1723 The incorporation 1707:1723 The incorporation of L-arginine (2%/4%) 1707:1745 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 6 43 theme Bacterial 840:848 arg1 composition 850:860 Bacterial composition 840:860 Bacterial composition in biofilms 840:872 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 1 44 theme modulatory 117:126 arg1 effect 128:133 the biofilm modulatory effect 105:133 the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms 105:198 OBJECTIVES To examine the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms. 35307476 12 45 theme Arg-F 1886:1890 arg1 varnish 1892:1898 that Arg-F varnish 1881:1898 that Arg-F varnish (at 2%/4% w/v 1881:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 0 46 theme arginine-fluoride 31:47 arg1 response 19:26 Biofilm modulatory response 0:26 Biofilm modulatory response of arginine-fluoride 0:47 Biofilm modulatory response of arginine-fluoride varnish on multi-species biofilm. 35307476 3 47 theme Multi-species 332:344 arg1 biofilms 346:353 Multi-species biofilms 332:353 Multi-species biofilms comprising Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii 332:437 Multi-species biofilms comprising Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii were grown on hydroxyapatite (HA) discs and treated with the Arg and F released from the experimental and control groups. 35307476 3 48 theme hydroxyapatite 453:466 arg1 discs 473:477 hydroxyapatite (HA) discs 453:477 hydroxyapatite (HA) discs 453:477 Multi-species biofilms comprising Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii were grown on hydroxyapatite (HA) discs and treated with the Arg and F released from the experimental and control groups. 35307476 8 49 theme greater 1169:1175 arg1 proportion 1177:1186 a significantly greater proportion 1153:1186 a significantly greater proportion of dead bacteria 1153:1203 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 10 50 theme % 1574:1574 arg1 Arg-NaF 1576:1582 2% Arg-NaF 1573:1582 2% Arg-NaF 1573:1582 Expression of gtfB, SMU.150, and nlmD were significantly downregulated in 4% Arg-NaF-treated biofilms; while 2% Arg-NaF enhanced the expression of arcA. 35307476 4 51 with discs 568:572 arg1 biofilms 587:594 treated biofilms 579:594 treated biofilms 579:594 The HA discs with treated biofilms were examined for biofilm composition. 35307476 10 52 theme arcA 1611:1614 arg1 expression 1597:1606 the expression 1593:1606 the expression of arcA 1593:1614 Expression of gtfB, SMU.150, and nlmD were significantly downregulated in 4% Arg-NaF-treated biofilms; while 2% Arg-NaF enhanced the expression of arcA. 35307476 9 53 theme carbohydrate 1293:1304 arg1 content 1306:1312 the carbohydrate content 1289:1312 the carbohydrate content of the biofilm 1289:1327 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 6 54 theme real-time 903:911 arg1 qPCR 953:956 qPCR 953:956 qPCR 953:956 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 6 54 theme real-time 903:911 arg1 reaction 943:950 viability real-time quantitative polymerase chain reaction 893:950 viability real-time quantitative polymerase chain reaction (qPCR) 893:957 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 9 55 theme biofilm 1321:1327 arg1 content 1306:1312 the carbohydrate content 1289:1312 the carbohydrate content of the biofilm 1289:1327 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 8 56 theme Arg-NaF 1077:1083 arg1 groups 1085:1090 the 2 and 4% Arg-NaF groups 1064:1090 the 2 and 4% Arg-NaF groups 1064:1090 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 2 57 theme NaF 290:292 arg1 control 323:329 the control 319:329 the control 319:329 METHODS Experimental varnishes were prepared by incorporating L-Arg (1, 2, and 4%) in 5% NaF varnish, which served as the control. 35307476 2 57 theme NaF 290:292 arg1 varnish 294:300 5% NaF varnish 287:300 5% NaF varnish 287:300 METHODS Experimental varnishes were prepared by incorporating L-Arg (1, 2, and 4%) in 5% NaF varnish, which served as the control. 35307476 9 58 theme 4 1340:1340 arg1 % 1341:1341 % 1341:1341 % 1341:1341 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 12 59 theme CLINICAL 1832:1839 arg1 SIGNIFICANCE 1841:1852 released Arg and F. CLINICAL SIGNIFICANCE 1812:1852 released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v 1812:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 1 60 theme varnish 166:172 arg1 effect 128:133 the biofilm modulatory effect 105:133 the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms 105:198 OBJECTIVES To examine the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms. 35307476 12 61 theme varnish 1796:1802 arg1 effect 1779:1784 the biofilm modulatory effect 1756:1784 the biofilm modulatory effect of 5% NaF varnish 1756:1802 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 8 62 dep RESULTS 1051:1057 arg1 Both 1059:1062 Both 1059:1062 Both 1059:1062 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 1 63 theme multi-species 177:189 arg1 biofilms 191:198 multi-species biofilms 177:198 multi-species biofilms 177:198 OBJECTIVES To examine the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms. 35307476 12 64 theme released 1812:1819 arg1 SIGNIFICANCE 1841:1852 released Arg and F. CLINICAL SIGNIFICANCE 1812:1852 released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v 1812:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 12 65 theme % 1908:1908 arg1 w/v 1910:1912 at 2%/4% w/v 1901:1912 at 2%/4% w/v 1901:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 5 66 theme live/dead 661:669 arg1 counts 671:676 The biofilm thickness and live/dead counts 635:676 counts 671:676 The biofilm thickness and live/dead counts were investigated using confocal microscopic imaging, while biofilm polysaccharides, proteins, and extracellular DNA (eDNA) were assessed spectrophotometrically. 35307476 8 67 theme 4 1128:1128 arg1 % 1129:1129 % 1129:1129 % 1129:1129 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 4 68 theme treated 579:585 arg1 biofilms 587:594 treated biofilms 579:594 treated biofilms 579:594 The HA discs with treated biofilms were examined for biofilm composition. 35307476 10 69 theme nlmD 1497:1500 arg1 Expression 1464:1473 Expression 1464:1473 Expression of gtfB, SMU.150, and nlmD 1464:1500 Expression of gtfB, SMU.150, and nlmD were significantly downregulated in 4% Arg-NaF-treated biofilms; while 2% Arg-NaF enhanced the expression of arcA. 35307476 8 70 theme Arg-NaF 1131:1137 arg1 group 1139:1143 the 4% Arg-NaF group 1124:1143 the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria 1124:1203 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 6 71 theme polymerase 926:935 arg1 qPCR 953:956 qPCR 953:956 qPCR 953:956 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 6 71 theme polymerase 926:935 arg1 reaction 943:950 viability real-time quantitative polymerase chain reaction 893:950 viability real-time quantitative polymerase chain reaction (qPCR) 893:957 Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). 35307476 9 72 theme eDNA 1405:1408 arg1 concentration 1388:1400 higher concentration 1381:1400 higher concentration of eDNA and proteins 1381:1421 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 12 73 theme % 1905:1905 arg1 w/v 1910:1912 at 2%/4% w/v 1901:1912 at 2%/4% w/v 1901:1912 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 11 74 theme % 1623:1623 arg1 Arg-NaF 1625:1631 2% Arg-NaF 1622:1631 2% Arg-NaF 1622:1631 Both 2% Arg-NaF and 4% Arg-NaF significantly increased the expression of sagP. 35307476 5 75 theme microscopic 711:721 arg1 imaging 723:729 confocal microscopic imaging 702:729 confocal microscopic imaging 702:729 The biofilm thickness and live/dead counts were investigated using confocal microscopic imaging, while biofilm polysaccharides, proteins, and extracellular DNA (eDNA) were assessed spectrophotometrically. 35307476 9 76 theme Arg-NaF-treated 1343:1357 arg1 biofilms 1359:1366 the 4% Arg-NaF-treated biofilms 1336:1366 the 4% Arg-NaF-treated biofilms 1336:1366 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 9 77 theme proteins 1414:1421 arg1 concentration 1388:1400 higher concentration 1381:1400 higher concentration of eDNA and proteins 1381:1421 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 12 78 theme biofilm 1760:1766 arg1 effect 1779:1784 the biofilm modulatory effect 1756:1784 the biofilm modulatory effect of 5% NaF varnish 1756:1802 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 7 79 theme relative 964:971 arg1 RGE 990:992 RGE 990:992 RGE 990:992 The relative gene expression (RGE) was determined for gtfB, SMU.150, nlmD, arcA, and sagP. 35307476 7 79 theme relative 964:971 arg1 expression 978:987 The relative gene expression 960:987 The relative gene expression (RGE) 960:993 The relative gene expression (RGE) was determined for gtfB, SMU.150, nlmD, arcA, and sagP. 35307476 1 80 theme -fluoride 152:160 arg1 varnish 166:172 arginine (Arg)-fluoride (F) varnish 138:172 arginine (Arg)-fluoride (F) varnish 138:172 OBJECTIVES To examine the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms. 35307476 8 81 theme % 1225:1225 arg1 p < 0.001 1236:1244 p < 0.001 1236:1244 p < 0.001 1236:1244 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 8 81 theme % 1225:1225 arg1 Arg-NaF 1227:1233 1 and 2% Arg-NaF 1218:1233 Arg-NaF 1227:1233 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 11 82 theme % 1638:1638 arg1 Arg-NaF 1640:1646 4% Arg-NaF 1637:1646 4% Arg-NaF 1637:1646 Both 2% Arg-NaF and 4% Arg-NaF significantly increased the expression of sagP. 35307476 9 83 theme control 1439:1445 arg1 p < 0.001 1452:1460 p < 0.001 1452:1460 p < 0.001 1452:1460 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 9 83 theme control 1439:1445 arg1 NaF 1447:1449 the control NaF 1435:1449 the control NaF (p < 0.001) 1435:1461 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 3 84 attach released 510:517 arg2 Arg 500:502 Arg 500:502 Arg 500:502 Multi-species biofilms comprising Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii were grown on hydroxyapatite (HA) discs and treated with the Arg and F released from the experimental and control groups. 35307476 3 84 attach released 510:517 arg1 groups 553:558 the experimental and control groups 524:558 groups 553:558 Multi-species biofilms comprising Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii were grown on hydroxyapatite (HA) discs and treated with the Arg and F released from the experimental and control groups. 35307476 12 85 theme 5 1789:1789 arg1 % 1790:1790 % 1790:1790 % 1790:1790 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 10 86 theme 4 1538:1538 arg1 % 1539:1539 % 1539:1539 % 1539:1539 Expression of gtfB, SMU.150, and nlmD were significantly downregulated in 4% Arg-NaF-treated biofilms; while 2% Arg-NaF enhanced the expression of arcA. 35307476 0 87 theme modulatory 8:17 arg1 response 19:26 Biofilm modulatory response 0:26 Biofilm modulatory response of arginine-fluoride 0:47 Biofilm modulatory response of arginine-fluoride varnish on multi-species biofilm. 35307476 5 88 theme extracellular 777:789 arg1 eDNA 796:799 eDNA 796:799 eDNA 796:799 The biofilm thickness and live/dead counts were investigated using confocal microscopic imaging, while biofilm polysaccharides, proteins, and extracellular DNA (eDNA) were assessed spectrophotometrically. 35307476 5 88 theme extracellular 777:789 arg1 DNA 791:793 extracellular DNA 777:793 extracellular DNA (eDNA) 777:800 The biofilm thickness and live/dead counts were investigated using confocal microscopic imaging, while biofilm polysaccharides, proteins, and extracellular DNA (eDNA) were assessed spectrophotometrically. 35307476 1 89 theme biofilm 109:115 arg1 effect 128:133 the biofilm modulatory effect 105:133 the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms 105:198 OBJECTIVES To examine the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms. 35307476 5 90 theme biofilm 738:744 arg1 polysaccharides 746:760 biofilm polysaccharides 738:760 biofilm polysaccharides 738:760 The biofilm thickness and live/dead counts were investigated using confocal microscopic imaging, while biofilm polysaccharides, proteins, and extracellular DNA (eDNA) were assessed spectrophotometrically. 35307476 12 91 theme % 1741:1741 arg1 % 1744:1744 2%/4% 1740:1744 2%/4% 1740:1744 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 12 91 theme % 1741:1741 arg1 L-arginine 1728:1737 L-arginine 1728:1737 L-arginine (2%/4%) 1728:1745 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 10 92 theme Arg-NaF-treated 1541:1555 arg1 biofilms 1557:1564 4% Arg-NaF-treated biofilms 1538:1564 4% Arg-NaF-treated biofilms 1538:1564 Expression of gtfB, SMU.150, and nlmD were significantly downregulated in 4% Arg-NaF-treated biofilms; while 2% Arg-NaF enhanced the expression of arcA. 35307476 0 93 theme multi-species 60:72 arg1 biofilm 74:80 multi-species biofilm 60:80 multi-species biofilm 60:80 Biofilm modulatory response of arginine-fluoride varnish on multi-species biofilm. 35307476 9 94 theme Arg-NaF 1252:1258 arg1 groups 1260:1265 All Arg-NaF groups 1248:1265 All Arg-NaF groups 1248:1265 All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). 35307476 2 95 theme METHODS 201:207 arg1 varnishes 222:230 METHODS Experimental varnishes 201:230 METHODS Experimental varnishes 201:230 METHODS Experimental varnishes were prepared by incorporating L-Arg (1, 2, and 4%) in 5% NaF varnish, which served as the control. 35307476 2 96 theme % 288:288 arg1 control 323:329 the control 319:329 the control 319:329 METHODS Experimental varnishes were prepared by incorporating L-Arg (1, 2, and 4%) in 5% NaF varnish, which served as the control. 35307476 2 96 theme % 288:288 arg1 varnish 294:300 5% NaF varnish 287:300 5% NaF varnish 287:300 METHODS Experimental varnishes were prepared by incorporating L-Arg (1, 2, and 4%) in 5% NaF varnish, which served as the control. 35307476 10 97 theme 2 1573:1573 arg1 % 1574:1574 % 1574:1574 % 1574:1574 Expression of gtfB, SMU.150, and nlmD were significantly downregulated in 4% Arg-NaF-treated biofilms; while 2% Arg-NaF enhanced the expression of arcA. 35307476 13 98 theme high-risk 1973:1981 arg1 individuals 1983:1993 high-risk individuals 1973:1993 high-risk individuals 1973:1993 Arg) has the potential to modulate cariogenic biofilms in high-risk individuals. 35307476 12 99 theme study 1858:1862 arg1 results 1864:1870 The study results 1854:1870 The study results 1854:1870 CONCLUSION The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE The study results indicate that Arg-F varnish (at 2%/4% w/v. 35307476 8 100 theme dead 1191:1194 arg1 bacteria 1196:1203 dead bacteria 1191:1203 dead bacteria 1191:1203 RESULTS Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). 35307476 4 101 theme HA 565:566 arg1 discs 568:572 The HA discs 561:572 The HA discs with treated biofilms 561:594 The HA discs with treated biofilms were examined for biofilm composition. 35711643 6 0 theme WL 942:943 arg1 production 945:954 WL production 942:954 WL production 942:954 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 7 1 theme broth 976:980 arg1 viscosity 982:990 the broth viscosity 972:990 the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features 972:1157 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 1 2 theme other 219:223 arg1 fields 225:230 many other fields 214:230 many other fields 214:230 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 4 3 theme WL 524:525 arg1 production 531:540 WL gum production 524:540 WL gum production 524:540 WG and their effects on WL gum production and structure were investigated. 35711643 10 4 theme strains 1764:1770 arg1 construction 1727:1738 the construction 1723:1738 the construction of high WL gum-yielding strains and rheological property controlling in different industries 1723:1831 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 6 5 from enzymes 931:937 arg1 production 945:954 WL production 942:954 WL production 942:954 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 3 6 theme Sphingomonas 483:494 arg1 sp 496:497 Sphingomonas sp 483:497 Sphingomonas sp 483:497 Therefore, to gain insights into the bottlenecks of WL gum production by identifying the key enzymes in the WL gum biosynthesis pathway, more than 20 genes were over-expressed in Sphingomonas sp. 35711643 10 7 theme WL 1748:1749 arg1 strains 1764:1770 high WL gum-yielding strains 1743:1770 high WL gum-yielding strains 1743:1770 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 6 8 theme over-expression 766:780 arg1 strains 782:788 both atrB and atrD over-expression strains 747:788 strains 782:788 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 9 9 theme critical 1517:1524 arg1 factor 1526:1531 the critical factor 1513:1531 the critical factor 1513:1531 In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. 35711643 9 9 theme critical 1517:1524 arg1 content 1498:1504 acetyl content 1491:1504 acetyl content 1491:1504 In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. 35711643 10 10 theme rheological 1776:1786 arg1 property 1788:1795 rheological property 1776:1795 rheological property 1776:1795 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 5 11 theme over-expression 637:651 arg1 strain 653:658 welB over-expression strain 632:658 welB over-expression strain 632:658 Compared to the control strain, the WL gum production of welB over-expression strain was increased by 19.0 and 21.0% at 36 and 84 h, respectively. 35711643 7 12 theme strains 1016:1022 arg1 viscosity 982:990 the broth viscosity 972:990 the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features 972:1157 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 0 13 from Biosynthesis 44:55 arg1 Identification 0:13 Identification 0:13 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 0:102 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 0 13 from Biosynthesis 44:55 arg1 Control 95:101 Viscosity Control 85:101 Viscosity Control 85:101 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 1 14 used used 185:188 arg2 exopolysaccharide 130:146 an important microbial exopolysaccharide 107:146 an important microbial exopolysaccharide 107:146 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 1 14 used used 185:188 arg2 gum 165:167 the sphingan WL gum 149:167 the sphingan WL gum 149:167 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 10 15 theme different 1812:1820 arg1 industries 1822:1831 different industries 1812:1831 different industries 1812:1831 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 10 16 theme useful 1617:1622 arg1 information 1624:1634 useful information 1617:1634 useful information on the understanding of the bottlenecks of WL gum biosynthesis 1617:1697 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 5 17 theme gum 614:616 arg1 production 618:627 the WL gum production 607:627 the WL gum production of welB over-expression strain 607:658 Compared to the control strain, the WL gum production of welB over-expression strain was increased by 19.0 and 21.0% at 36 and 84 h, respectively. 35711643 1 18 theme microbial 120:128 arg1 gum 165:167 the sphingan WL gum 149:167 the sphingan WL gum 149:167 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 1 18 theme microbial 120:128 arg1 exopolysaccharide 130:146 an important microbial exopolysaccharide 107:146 an important microbial exopolysaccharide 107:146 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 7 19 theme viscosity 1212:1220 arg1 control 1222:1228 viscosity control 1212:1228 viscosity control 1212:1228 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 9 20 theme WL 1590:1591 arg1 gum 1593:1595 WL gum 1590:1595 WL gum 1590:1595 In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. 35711643 8 21 theme total 1340:1344 arg1 content 1352:1358 total sugar content 1340:1358 total sugar content 1340:1358 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 21 theme total 1340:1344 arg1 composition 1379:1389 not the key composition 1367:1389 not the key composition 1367:1389 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 21 theme total 1340:1344 arg1 acid 1331:1334 uronic acid 1324:1334 uronic acid 1324:1334 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 21 theme total 1340:1344 arg1 genes 1306:1310 only a few genes 1295:1310 only a few genes 1295:1310 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 0 22 theme Critical 61:68 arg1 Composition 70:80 Critical Composition 61:80 Critical Composition 61:80 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 1 23 theme sphingan 153:160 arg1 gum 165:167 the sphingan WL gum 149:167 the sphingan WL gum 149:167 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 1 23 theme sphingan 153:160 arg1 exopolysaccharide 130:146 an important microbial exopolysaccharide 107:146 an important microbial exopolysaccharide 107:146 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 0 24 from Identification 0:13 arg1 Biosynthesis 44:55 WL Gum Biosynthesis 37:55 WL Gum Biosynthesis 37:55 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 0 24 from Identification 0:13 arg1 Composition 70:80 Critical Composition 61:80 Critical Composition 61:80 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 10 25 from information 1624:1634 arg1 understanding 1643:1655 the understanding 1639:1655 the understanding of the bottlenecks of WL gum biosynthesis 1639:1697 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 7 26 theme welJ 1050:1053 arg1 strain 1071:1076 the welJ over-expression strain 1046:1076 the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features 1046:1157 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 7 26 theme welJ 1050:1053 arg1 strains 1016:1022 most over-expression strains 995:1022 most over-expression strains decreased 995:1032 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 6 27 theme key 927:929 arg1 enzymes 931:937 the key enzymes 923:937 the key enzymes in WL production 923:954 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 0 28 from Enzymes 26:32 arg1 Biosynthesis 44:55 WL Gum Biosynthesis 37:55 WL Gum Biosynthesis 37:55 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 0 28 from Enzymes 26:32 arg1 Composition 70:80 Critical Composition 61:80 Critical Composition 61:80 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 8 29 theme acid 1242:1245 arg1 content 1247:1253 The uronic acid content 1231:1253 The uronic acid content 1231:1253 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 4 30 from WG 500:501 arg1 production 531:540 WL gum production 524:540 WL gum production 524:540 WG and their effects on WL gum production and structure were investigated. 35711643 4 30 from WG 500:501 arg1 structure 546:554 structure 546:554 structure 546:554 WG and their effects on WL gum production and structure were investigated. 35711643 5 31 theme strain 653:658 arg1 production 618:627 the WL gum production 607:627 the WL gum production of welB over-expression strain 607:658 Compared to the control strain, the WL gum production of welB over-expression strain was increased by 19.0 and 21.0% at 36 and 84 h, respectively. 35711643 7 32 theme critical 1189:1196 arg1 components 1198:1207 the critical components 1185:1207 the critical components in viscosity control 1185:1228 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 6 33 theme atrD 761:764 arg1 strains 782:788 both atrB and atrD over-expression strains 747:788 strains 782:788 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 3 34 theme gum 359:361 arg1 production 363:372 WL gum production 356:372 WL gum production 356:372 Therefore, to gain insights into the bottlenecks of WL gum production by identifying the key enzymes in the WL gum biosynthesis pathway, more than 20 genes were over-expressed in Sphingomonas sp. 35711643 10 35 theme gum 1682:1684 arg1 biosynthesis 1686:1697 WL gum biosynthesis 1679:1697 WL gum biosynthesis 1679:1697 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 8 36 theme sugar 1265:1269 arg1 content 1271:1277 total sugar content 1259:1277 total sugar content 1259:1277 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 7 37 theme over-expression 1000:1014 arg1 strain 1071:1076 the welJ over-expression strain 1046:1076 the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features 1046:1157 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 7 37 theme over-expression 1000:1014 arg1 strains 1016:1022 most over-expression strains 995:1022 most over-expression strains decreased 995:1032 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 0 38 theme Enzymes 26:32 arg1 Identification 0:13 Identification 0:13 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 0:102 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 6 39 theme atrB 752:755 arg1 production 733:742 The WL gum production 722:742 The WL gum production of both atrB and atrD over-expression strains 722:788 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 0 40 theme WL 37:38 arg1 Biosynthesis 44:55 WL Gum Biosynthesis 37:55 WL Gum Biosynthesis 37:55 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 2 41 theme wider 285:289 arg1 application 291:301 its wider application 281:301 its wider application 281:301 However, its lower production is still limiting its wider application. 35711643 6 42 theme gum 729:731 arg1 production 733:742 The WL gum production 722:742 The WL gum production of both atrB and atrD over-expression strains 722:788 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 9 43 theme most 1462:1465 arg1 genes 1467:1471 most genes 1462:1471 most genes 1462:1471 In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. 35711643 4 44 theme gum 527:529 arg1 production 531:540 WL gum production 524:540 WL gum production 524:540 WG and their effects on WL gum production and structure were investigated. 35711643 7 45 from components 1198:1207 arg1 control 1222:1228 viscosity control 1212:1228 viscosity control 1212:1228 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 7 46 theme 84 h. 1116:1120 arg1 Polysaccharides 1122:1136 84 h. Polysaccharides' structural features 1116:1157 84 h. Polysaccharides' structural features 1116:1157 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 1 47 theme many 214:217 arg1 fields 225:230 many other fields 214:230 many other fields 214:230 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 5 48 theme control 591:597 arg1 strain 599:604 the control strain 587:604 the control strain 587:604 Compared to the control strain, the WL gum production of welB over-expression strain was increased by 19.0 and 21.0% at 36 and 84 h, respectively. 35711643 2 49 theme lower 246:250 arg1 production 252:261 its lower production 242:261 its lower production 242:261 However, its lower production is still limiting its wider application. 35711643 9 50 theme acetyl 1491:1496 arg1 factor 1526:1531 the critical factor 1513:1531 the critical factor 1513:1531 In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. 35711643 9 50 theme acetyl 1491:1496 arg1 content 1498:1504 acetyl content 1491:1504 acetyl content 1491:1504 In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. 35711643 10 51 theme gum-yielding 1751:1762 arg1 strains 1764:1770 high WL gum-yielding strains 1743:1770 high WL gum-yielding strains 1743:1770 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 1 52 theme WL 162:163 arg1 gum 165:167 the sphingan WL gum 149:167 the sphingan WL gum 149:167 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 1 52 theme WL 162:163 arg1 exopolysaccharide 130:146 an important microbial exopolysaccharide 107:146 an important microbial exopolysaccharide 107:146 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 6 53 theme strains 782:788 arg1 production 733:742 The WL gum production 722:742 The WL gum production of both atrB and atrD over-expression strains 722:788 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 10 54 theme high 1743:1746 arg1 strains 1764:1770 high WL gum-yielding strains 1743:1770 high WL gum-yielding strains 1743:1770 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 6 55 theme control 860:866 arg1 strain 868:873 the control strain 856:873 the control strain 856:873 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 10 56 theme property 1788:1795 arg1 construction 1727:1738 the construction 1723:1738 the construction of high WL gum-yielding strains and rheological property controlling in different industries 1723:1831 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 0 57 from Composition 70:80 arg1 Identification 0:13 Identification 0:13 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 0:102 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 0 57 from Composition 70:80 arg1 Control 95:101 Viscosity Control 85:101 Viscosity Control 85:101 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 5 58 theme welB 632:635 arg1 strain 653:658 welB over-expression strain 632:658 welB over-expression strain 632:658 Compared to the control strain, the WL gum production of welB over-expression strain was increased by 19.0 and 21.0% at 36 and 84 h, respectively. 35711643 7 59 theme over-expression 1055:1069 arg1 strain 1071:1076 the welJ over-expression strain 1046:1076 the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features 1046:1157 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 7 59 theme over-expression 1055:1069 arg1 strains 1016:1022 most over-expression strains 995:1022 most over-expression strains decreased 995:1032 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 6 60 dep 36 h. 878:882 arg1 enzymes 931:937 the key enzymes 923:937 the key enzymes in WL production 923:954 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 8 61 theme uronic 1324:1329 arg1 content 1352:1358 total sugar content 1340:1358 total sugar content 1340:1358 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 61 theme uronic 1324:1329 arg1 composition 1379:1389 not the key composition 1367:1389 not the key composition 1367:1389 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 61 theme uronic 1324:1329 arg1 acid 1331:1334 uronic acid 1324:1334 uronic acid 1324:1334 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 61 theme uronic 1324:1329 arg1 genes 1306:1310 only a few genes 1295:1310 only a few genes 1295:1310 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 5 62 theme WL 611:612 arg1 production 618:627 the WL gum production 607:627 the WL gum production of welB over-expression strain 607:658 Compared to the control strain, the WL gum production of welB over-expression strain was increased by 19.0 and 21.0% at 36 and 84 h, respectively. 35711643 10 63 theme bottlenecks 1664:1674 arg1 understanding 1643:1655 the understanding 1639:1655 the understanding of the bottlenecks of WL gum biosynthesis 1639:1697 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 1 64 theme important 110:118 arg1 gum 165:167 the sphingan WL gum 149:167 the sphingan WL gum 149:167 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 1 64 theme important 110:118 arg1 exopolysaccharide 130:146 an important microbial exopolysaccharide 107:146 an important microbial exopolysaccharide 107:146 As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. 35711643 9 65 theme apparent 1568:1575 arg1 viscosity 1577:1585 the apparent viscosity 1564:1585 the apparent viscosity of WL gum 1564:1595 In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. 35711643 3 66 theme gum 415:417 arg1 pathway 432:438 the WL gum biosynthesis pathway 408:438 the WL gum biosynthesis pathway 408:438 Therefore, to gain insights into the bottlenecks of WL gum production by identifying the key enzymes in the WL gum biosynthesis pathway, more than 20 genes were over-expressed in Sphingomonas sp. 35711643 8 67 theme sugar 1346:1350 arg1 content 1352:1358 total sugar content 1340:1358 total sugar content 1340:1358 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 67 theme sugar 1346:1350 arg1 composition 1379:1389 not the key composition 1367:1389 not the key composition 1367:1389 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 67 theme sugar 1346:1350 arg1 acid 1331:1334 uronic acid 1324:1334 uronic acid 1324:1334 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 67 theme sugar 1346:1350 arg1 genes 1306:1310 only a few genes 1295:1310 only a few genes 1295:1310 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 9 68 theme gum 1593:1595 arg1 viscosity 1577:1585 the apparent viscosity 1564:1585 the apparent viscosity of WL gum 1564:1595 In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. 35711643 0 69 theme Viscosity 85:93 arg1 Control 95:101 Viscosity Control 85:101 Viscosity Control 85:101 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 7 70 dep Polysaccharides 1122:1136 arg1 features 1150:1157 structural features 1139:1157 84 h. Polysaccharides' structural features 1116:1157 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 4 71 from effects 513:519 arg1 production 531:540 WL gum production 524:540 WL gum production 524:540 WG and their effects on WL gum production and structure were investigated. 35711643 4 71 from effects 513:519 arg1 structure 546:554 structure 546:554 structure 546:554 WG and their effects on WL gum production and structure were investigated. 35711643 8 72 theme key 1375:1377 arg1 content 1352:1358 total sugar content 1340:1358 total sugar content 1340:1358 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 72 theme key 1375:1377 arg1 composition 1379:1389 not the key composition 1367:1389 not the key composition 1367:1389 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 72 theme key 1375:1377 arg1 acid 1331:1334 uronic acid 1324:1334 uronic acid 1324:1334 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 8 72 theme key 1375:1377 arg1 genes 1306:1310 only a few genes 1295:1310 only a few genes 1295:1310 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 3 73 theme key 393:395 arg1 enzymes 397:403 the key enzymes 389:403 the key enzymes in the WL gum biosynthesis pathway 389:438 Therefore, to gain insights into the bottlenecks of WL gum production by identifying the key enzymes in the WL gum biosynthesis pathway, more than 20 genes were over-expressed in Sphingomonas sp. 35711643 8 74 theme uronic 1235:1240 arg1 content 1247:1253 The uronic acid content 1231:1253 The uronic acid content 1231:1253 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 0 75 theme Key 22:24 arg1 Enzymes 26:32 the Key Enzymes 18:32 the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control 18:101 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 9 76 theme acetyl 1411:1416 arg1 degrees 1418:1424 the acetyl degrees 1407:1424 the acetyl degrees 1407:1424 In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. 35711643 10 77 theme biosynthesis 1686:1697 arg1 bottlenecks 1664:1674 the bottlenecks 1660:1674 the bottlenecks of WL gum biosynthesis 1660:1697 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 3 78 theme WL 412:413 arg1 pathway 432:438 the WL gum biosynthesis pathway 408:438 the WL gum biosynthesis pathway 408:438 Therefore, to gain insights into the bottlenecks of WL gum production by identifying the key enzymes in the WL gum biosynthesis pathway, more than 20 genes were over-expressed in Sphingomonas sp. 35711643 7 79 theme most 995:998 arg1 strain 1071:1076 the welJ over-expression strain 1046:1076 the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features 1046:1157 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 7 79 theme most 995:998 arg1 strains 1016:1022 most over-expression strains 995:1022 most over-expression strains decreased 995:1032 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 3 80 theme production 363:372 arg1 bottlenecks 341:351 the bottlenecks 337:351 the bottlenecks of WL gum production 337:372 Therefore, to gain insights into the bottlenecks of WL gum production by identifying the key enzymes in the WL gum biosynthesis pathway, more than 20 genes were over-expressed in Sphingomonas sp. 35711643 10 81 theme WL 1679:1680 arg1 biosynthesis 1686:1697 WL gum biosynthesis 1679:1697 WL gum biosynthesis 1679:1697 This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries. 35711643 8 82 theme total 1259:1263 arg1 content 1271:1277 total sugar content 1259:1277 total sugar content 1259:1277 The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. 35711643 3 83 from enzymes 397:403 arg1 pathway 432:438 the WL gum biosynthesis pathway 408:438 the WL gum biosynthesis pathway 408:438 Therefore, to gain insights into the bottlenecks of WL gum production by identifying the key enzymes in the WL gum biosynthesis pathway, more than 20 genes were over-expressed in Sphingomonas sp. 35711643 0 84 theme Gum 40:42 arg1 Biosynthesis 44:55 WL Gum Biosynthesis 37:55 WL Gum Biosynthesis 37:55 Identification of the Key Enzymes in WL Gum Biosynthesis and Critical Composition in Viscosity Control. 35711643 7 85 theme structural 1139:1148 arg1 features 1150:1157 structural features 1139:1157 84 h. Polysaccharides' structural features 1116:1157 Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. 35711643 3 86 theme WL 356:357 arg1 production 363:372 WL gum production 356:372 WL gum production 356:372 Therefore, to gain insights into the bottlenecks of WL gum production by identifying the key enzymes in the WL gum biosynthesis pathway, more than 20 genes were over-expressed in Sphingomonas sp. 35711643 3 87 theme biosynthesis 419:430 arg1 pathway 432:438 the WL gum biosynthesis pathway 408:438 the WL gum biosynthesis pathway 408:438 Therefore, to gain insights into the bottlenecks of WL gum production by identifying the key enzymes in the WL gum biosynthesis pathway, more than 20 genes were over-expressed in Sphingomonas sp. 35711643 6 88 theme WL 726:727 arg1 production 733:742 The WL gum production 722:742 The WL gum production of both atrB and atrD over-expression strains 722:788 The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. 35711643 9 89 theme genes 1467:1471 arg1 over-expression 1443:1457 over-expression 1443:1457 over-expression of most genes, which meant that acetyl content may be the critical factor 1443:1531 In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. 36561459 0 0 theme alga 24:27 arg1 Spirogyra 29:37 the green alga Spirogyra 14:37 the green alga Spirogyra 14:37 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 36561459 13 1 located found 2378:2382 arg1 state 2402:2406 the vegetative state 2387:2406 the vegetative state 2387:2406 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 13 1 located found 2378:2382 arg2 integration 2310:2320 the integration 2306:2320 the integration of highly resistant components in the cell wall 2306:2368 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 13 1 located found 2378:2382 arg2 arrangement 2274:2284 the newly discovered special three-dimensional arrangement 2227:2284 the newly discovered special three-dimensional arrangement of microfibrils 2227:2300 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 14 2 theme potential 2503:2511 arg1 role 2517:2520 its potential key role 2499:2520 its potential key role in the terrestrial colonization and plant evolution 2499:2572 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 2 3 theme vegetative 336:345 arg1 cells 347:351 vegetative cells 336:351 vegetative cells 336:351 The transition from aquatic to terrestrial environments requires adaptations in the physiology of vegetative cells and in the structural properties of their cell walls. 36561459 12 4 theme internal 2113:2120 arg1 structure 2122:2130 a highly complex internal structure 2096:2130 a highly complex internal structure as well as aromatics 2096:2151 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 7 5 with polysaccharides 1179:1193 arg1 appearance 1226:1235 different ultrastructural appearance 1200:1235 different ultrastructural appearance 1200:1235 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 2 6 theme aquatic 258:264 arg1 environments 281:292 aquatic to terrestrial environments 258:292 aquatic to terrestrial environments 258:292 The transition from aquatic to terrestrial environments requires adaptations in the physiology of vegetative cells and in the structural properties of their cell walls. 36561459 13 7 theme microfibrils 2289:2300 arg1 integration 2310:2320 the integration 2306:2320 the integration of highly resistant components in the cell wall 2306:2368 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 13 7 theme microfibrils 2289:2300 arg1 arrangement 2274:2284 the newly discovered special three-dimensional arrangement 2227:2284 the newly discovered special three-dimensional arrangement of microfibrils 2227:2300 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 2 8 theme structural 364:373 arg1 properties 375:384 the structural properties 360:384 the structural properties of their cell walls 360:404 The transition from aquatic to terrestrial environments requires adaptations in the physiology of vegetative cells and in the structural properties of their cell walls. 36561459 4 9 theme field 668:672 arg1 sp 692:693 field sampled Spirogyra sp 668:693 field sampled Spirogyra sp 668:693 We investigated the structure and chemical composition of field sampled Spirogyra sp. 36561459 13 10 theme three-dimensional 2256:2272 arg1 arrangement 2274:2284 the newly discovered special three-dimensional arrangement 2227:2284 the newly discovered special three-dimensional arrangement of microfibrils 2227:2300 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 14 11 theme cell 2485:2488 arg1 wall 2490:2493 the intricate zygospore cell wall 2461:2493 the intricate zygospore cell wall 2461:2493 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 3 12 theme multi-layered 531:543 arg1 walls 550:554 unique multi-layered cell walls 524:554 unique multi-layered cell walls 524:554 Sexual reproduction occurs in Zygnematophyceae by conjugation and results in the formation of zygospores, possessing unique multi-layered cell walls, which might have been crucial in terrestrialization. 36561459 1 13 theme group 156:160 arg1 class 111:115 a class 109:115 a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats 109:235 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 1 13 theme group 156:160 arg1 Zygnematophyceae 91:106 Zygnematophyceae 91:106 Zygnematophyceae 91:106 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 4 14 theme Spirogyra 682:690 arg1 sp 692:693 field sampled Spirogyra sp 668:693 field sampled Spirogyra sp 668:693 We investigated the structure and chemical composition of field sampled Spirogyra sp. 36561459 10 15 theme wall 1710:1713 arg1 differentiation 1677:1691 the tripartite differentiation 1662:1691 the tripartite differentiation of the zygospore wall 1662:1713 While the tripartite differentiation of the zygospore wall is well established in Zygnematopyhceae, Spirogyra showed cellulose fibrils arranged in a helicoidal pattern in the endo- and exospore. 36561459 14 16 theme intricate 2465:2473 arg1 wall 2490:2493 the intricate zygospore cell wall 2461:2493 the intricate zygospore cell wall 2461:2493 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 1 17 theme land 165:168 arg1 plants 170:175 land plants 165:175 land plants 165:175 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 6 18 theme subcellular 1029:1039 arg1 organization 1041:1052 the subcellular organization 1025:1052 the subcellular organization 1025:1052 This comprehensive analysis allowed the detection of the subcellular organization and showed three main layers of the zygospore wall, termed endo-, meso- and exospore. 36561459 9 19 theme moss 1533:1536 arg1 spores 1538:1543 moss spores 1533:1543 moss spores 1533:1543 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 11 20 theme wall 1912:1915 arg1 formation 1917:1925 early zygospore wall formation 1896:1925 early zygospore wall formation 1896:1925 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 3 21 theme zygospores 501:510 arg1 formation 488:496 the formation 484:496 the formation of zygospores, possessing unique multi-layered cell walls, which might have been crucial in terrestrialization 484:607 Sexual reproduction occurs in Zygnematophyceae by conjugation and results in the formation of zygospores, possessing unique multi-layered cell walls, which might have been crucial in terrestrialization. 36561459 5 22 theme high 873:876 arg1 substitution 910:921 high pressure freeze fixation/freeze substitution 873:921 high pressure freeze fixation/freeze substitution 873:921 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 8 23 theme possible 1358:1365 arg1 composition 1376:1386 The possible chemical composition 1354:1386 The possible chemical composition 1354:1386 The possible chemical composition remains elusive, but algaenan or a sporopollenin-like material is suggested. 36561459 5 24 theme microscopical 729:741 arg1 techniques 764:773 multiple microscopical and spectral imaging techniques 720:773 multiple microscopical and spectral imaging techniques 720:773 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 13 25 theme discovered 2237:2246 arg1 arrangement 2274:2284 the newly discovered special three-dimensional arrangement 2227:2284 the newly discovered special three-dimensional arrangement of microfibrils 2227:2300 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 5 26 theme electron 843:850 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 26 theme electron 843:850 arg1 microscopy 852:861 transmission electron microscopy 830:861 transmission electron microscopy following high pressure freeze fixation/freeze substitution 830:921 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 27 theme freeze 887:892 arg1 substitution 910:921 high pressure freeze fixation/freeze substitution 873:921 high pressure freeze fixation/freeze substitution 873:921 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 12 28 theme formed 2070:2075 arg1 zygospores 2077:2086 the sexually formed zygospores 2057:2086 the sexually formed zygospores 2057:2086 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 1 29 from live 192:195 arg1 aquatic 200:206 aquatic 200:206 aquatic to semi-terrestrial habitats 200:235 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 14 30 from role 2517:2520 arg1 colonization 2541:2552 the terrestrial colonization 2525:2552 the terrestrial colonization 2525:2552 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 14 30 from role 2517:2520 arg1 evolution 2564:2572 plant evolution 2558:2572 plant evolution 2558:2572 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 5 31 theme cell 706:709 arg1 microscopy 818:827 confocal laser scanning microscopy 794:827 confocal laser scanning microscopy 794:827 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 31 theme cell 706:709 arg1 spectroscopy 930:941 Raman spectroscopy 924:941 Raman spectroscopy 924:941 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 31 theme cell 706:709 arg1 microscopy 782:791 light microscopy 776:791 light microscopy 776:791 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 31 theme cell 706:709 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 31 theme cell 706:709 arg1 microscopy 852:861 transmission electron microscopy 830:861 transmission electron microscopy following high pressure freeze fixation/freeze substitution 830:921 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 31 theme cell 706:709 arg1 microscopy 960:969 atomic force microscopy 947:969 atomic force microscopy 947:969 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 9 32 theme protective 1587:1596 arg1 function 1598:1605 a protective function 1585:1605 a protective function against desiccation stress and high irradiation 1585:1653 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 11 33 theme Initial 1851:1857 arg1 incorporation 1859:1871 Initial incorporation 1851:1871 Initial incorporation of lipid bodies during early zygospore wall formation 1851:1925 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 5 34 theme light 776:780 arg1 microscopy 782:791 light microscopy 776:791 light microscopy 776:791 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 34 theme light 776:780 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 35 theme laser 803:807 arg1 microscopy 818:827 confocal laser scanning microscopy 794:827 confocal laser scanning microscopy 794:827 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 35 theme laser 803:807 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 9 36 theme desiccation 1615:1625 arg1 stress 1627:1632 desiccation stress 1615:1632 desiccation stress 1615:1632 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 2 37 from environments 281:292 arg1 transition 242:251 The transition 238:251 The transition from aquatic to terrestrial environments 238:292 The transition from aquatic to terrestrial environments requires adaptations in the physiology of vegetative cells and in the structural properties of their cell walls. 36561459 5 38 dep walls 711:715 arg1 microscopy 818:827 confocal laser scanning microscopy 794:827 confocal laser scanning microscopy 794:827 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 38 dep walls 711:715 arg1 spectroscopy 930:941 Raman spectroscopy 924:941 Raman spectroscopy 924:941 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 38 dep walls 711:715 arg1 microscopy 782:791 light microscopy 776:791 light microscopy 776:791 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 38 dep walls 711:715 arg1 microscopy 960:969 atomic force microscopy 947:969 atomic force microscopy 947:969 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 38 dep walls 711:715 arg1 microscopy 852:861 transmission electron microscopy 830:861 transmission electron microscopy following high pressure freeze fixation/freeze substitution 830:921 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 38 dep walls 711:715 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 13 39 from components 2342:2351 arg1 wall 2365:2368 the cell wall 2356:2368 the cell wall 2356:2368 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 12 40 theme protective 2171:2180 arg1 compounds 2182:2190 protective compounds 2171:2190 protective compounds 2171:2190 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 14 41 theme methods 2424:2430 arg1 methods 2424:2430 methods 2424:2430 methods 2424:2430 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 14 41 theme methods 2424:2430 arg1 variety 2413:2419 The variety 2409:2419 The variety of methods 2409:2430 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 11 42 theme early 1896:1900 arg1 formation 1917:1925 early zygospore wall formation 1896:1925 early zygospore wall formation 1896:1925 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 0 43 theme structural 58:67 arg1 imaging 82:88 structural and chemical imaging 58:88 structural and chemical imaging 58:88 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 36561459 5 44 theme force 954:958 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 44 theme force 954:958 arg1 microscopy 960:969 atomic force microscopy 947:969 atomic force microscopy 947:969 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 8 45 theme sporopollenin-like 1423:1440 arg1 material 1442:1449 a sporopollenin-like material 1421:1449 a sporopollenin-like material 1421:1449 The possible chemical composition remains elusive, but algaenan or a sporopollenin-like material is suggested. 36561459 11 46 theme bodies 1882:1887 arg1 incorporation 1859:1871 Initial incorporation 1851:1871 Initial incorporation of lipid bodies during early zygospore wall formation 1851:1925 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 0 47 theme chemical 73:80 arg1 imaging 82:88 structural and chemical imaging 58:88 structural and chemical imaging 58:88 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 36561459 12 48 theme cell 2044:2047 arg1 wall 2049:2052 the cell wall 2040:2052 the cell wall of the sexually formed zygospores 2040:2086 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 13 49 from wall 2365:2368 arg1 integration 2310:2320 the integration 2306:2320 the integration of highly resistant components in the cell wall 2306:2368 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 13 49 from wall 2365:2368 arg1 arrangement 2274:2284 the newly discovered special three-dimensional arrangement 2227:2284 the newly discovered special three-dimensional arrangement of microfibrils 2227:2300 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 10 50 theme cellulose 1773:1781 arg1 fibrils 1783:1789 cellulose fibrils 1773:1789 cellulose fibrils arranged in a helicoidal pattern in the endo- and exospore 1773:1848 While the tripartite differentiation of the zygospore wall is well established in Zygnematopyhceae, Spirogyra showed cellulose fibrils arranged in a helicoidal pattern in the endo- and exospore. 36561459 7 51 theme dense 1259:1263 arg1 layer 1272:1276 the electron dense middle layer 1246:1276 the electron dense middle layer 1246:1276 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 5 52 theme confocal 794:801 arg1 microscopy 818:827 confocal laser scanning microscopy 794:827 confocal laser scanning microscopy 794:827 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 52 theme confocal 794:801 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 12 53 dep possess 2088:2094 arg1 leading 2196:2202 leading 2196:2202 leading to impregnation 2196:2218 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 12 53 dep possess 2088:2094 arg1 acting 2161:2166 acting 2161:2166 acting as protective compounds 2161:2190 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 11 54 from role 1963:1966 arg1 synthesis 1996:2004 zygospore wall synthesis 1981:2004 zygospore wall synthesis 1981:2004 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 3 55 theme Sexual 407:412 arg1 reproduction 414:425 Sexual reproduction 407:425 Sexual reproduction 407:425 Sexual reproduction occurs in Zygnematophyceae by conjugation and results in the formation of zygospores, possessing unique multi-layered cell walls, which might have been crucial in terrestrialization. 36561459 5 56 theme transmission 830:841 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 56 theme transmission 830:841 arg1 microscopy 852:861 transmission electron microscopy 830:861 transmission electron microscopy following high pressure freeze fixation/freeze substitution 830:921 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 9 57 located found 1524:1528 arg2 compounds 1473:1481 Similar compounds 1465:1481 Similar compounds with a non-hydrolysable character 1465:1515 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 9 57 located found 1524:1528 arg1 pollen 1549:1554 pollen 1549:1554 pollen 1549:1554 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 9 57 located found 1524:1528 arg1 spores 1538:1543 moss spores 1533:1543 moss spores 1533:1543 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 3 58 from crucial 579:585 arg1 terrestrialization 590:607 terrestrialization 590:607 terrestrialization 590:607 Sexual reproduction occurs in Zygnematophyceae by conjugation and results in the formation of zygospores, possessing unique multi-layered cell walls, which might have been crucial in terrestrialization. 36561459 3 59 from terrestrialization 590:607 arg1 crucial 579:585 crucial 579:585 crucial 579:585 Sexual reproduction occurs in Zygnematophyceae by conjugation and results in the formation of zygospores, possessing unique multi-layered cell walls, which might have been crucial in terrestrialization. 36561459 2 60 theme cell 395:398 arg1 walls 400:404 their cell walls 389:404 their cell walls 389:404 The transition from aquatic to terrestrial environments requires adaptations in the physiology of vegetative cells and in the structural properties of their cell walls. 36561459 1 61 theme sister 149:154 arg1 group 156:160 sister group 149:160 sister group 149:160 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 7 62 theme ultrastructural 1210:1224 arg1 appearance 1226:1235 different ultrastructural appearance 1200:1235 different ultrastructural appearance 1200:1235 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 6 63 theme wall 1100:1103 arg1 layers 1076:1081 three main layers 1065:1081 three main layers of the zygospore wall, termed endo-, meso- and exospore 1065:1137 This comprehensive analysis allowed the detection of the subcellular organization and showed three main layers of the zygospore wall, termed endo-, meso- and exospore. 36561459 13 64 from integration 2310:2320 arg1 wall 2365:2368 the cell wall 2356:2368 the cell wall 2356:2368 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 9 65 theme Similar 1465:1471 arg1 compounds 1473:1481 Similar compounds 1465:1481 Similar compounds with a non-hydrolysable character 1465:1515 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 4 66 dep structure 630:638 arg1 the 626:628 the 626:628 the 626:628 We investigated the structure and chemical composition of field sampled Spirogyra sp. 36561459 12 67 contain possess 2088:2094 arg2 structure 2122:2130 a highly complex internal structure 2096:2130 a highly complex internal structure as well as aromatics 2096:2151 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 12 67 contain possess 2088:2094 arg2 aromatics 2143:2151 aromatics 2143:2151 a highly complex internal structure as well as aromatics 2096:2151 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 12 67 contain possess 2088:2094 arg1 wall 2049:2052 the cell wall 2040:2052 the cell wall of the sexually formed zygospores 2040:2086 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 14 68 theme terrestrial 2529:2539 arg1 colonization 2541:2552 the terrestrial colonization 2525:2552 the terrestrial colonization 2525:2552 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 11 69 theme key 1959:1961 arg1 role 1963:1966 a key role 1957:1966 a key role of lipids in zygospore wall synthesis 1957:2004 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 1 70 theme live 192:195 arg1 Embryophytes 178:189 Embryophytes 178:189 Embryophytes 178:189 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 1 70 theme live 192:195 arg1 algae 139:143 streptophyte green algae 120:143 streptophyte green algae 120:143 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 1 71 theme green 133:137 arg1 Embryophytes 178:189 Embryophytes 178:189 Embryophytes 178:189 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 1 71 theme green 133:137 arg1 algae 139:143 streptophyte green algae 120:143 streptophyte green algae 120:143 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 7 72 contain contains 1278:1285 arg2 compounds 1296:1304 aromatic compounds 1287:1304 aromatic compounds 1287:1304 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 7 72 contain contains 1278:1285 arg1 layer 1272:1276 the electron dense middle layer 1246:1276 the electron dense middle layer 1246:1276 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 11 73 theme wall 1991:1994 arg1 synthesis 1996:2004 zygospore wall synthesis 1981:2004 zygospore wall synthesis 1981:2004 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 9 74 theme non-hydrolysable 1490:1505 arg1 character 1507:1515 a non-hydrolysable character 1488:1515 a non-hydrolysable character 1488:1515 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 0 75 theme new 40:42 arg1 insights 44:51 new insights 40:51 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 0:89 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 36561459 6 76 theme comprehensive 977:989 arg1 analysis 991:998 This comprehensive analysis 972:998 This comprehensive analysis 972:998 This comprehensive analysis allowed the detection of the subcellular organization and showed three main layers of the zygospore wall, termed endo-, meso- and exospore. 36561459 0 77 dep Zygospores 0:9 arg1 insights 44:51 new insights 40:51 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 0:89 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 36561459 7 78 theme Raman 1334:1338 arg1 spectroscopy 1340:1351 Raman spectroscopy 1334:1351 Raman spectroscopy 1334:1351 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 14 79 theme key 2513:2515 arg1 role 2517:2520 its potential key role 2499:2520 its potential key role in the terrestrial colonization and plant evolution 2499:2572 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 2 80 theme cells 347:351 arg1 physiology 322:331 the physiology 318:331 the physiology of vegetative cells 318:351 The transition from aquatic to terrestrial environments requires adaptations in the physiology of vegetative cells and in the structural properties of their cell walls. 36561459 1 81 theme semi-terrestrial 211:226 arg1 habitats 228:235 semi-terrestrial habitats 211:235 semi-terrestrial habitats 211:235 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 10 82 from pattern 1816:1822 arg1 exospore 1841:1848 exospore 1841:1848 exospore 1841:1848 While the tripartite differentiation of the zygospore wall is well established in Zygnematopyhceae, Spirogyra showed cellulose fibrils arranged in a helicoidal pattern in the endo- and exospore. 36561459 10 82 from pattern 1816:1822 arg1 endo- 1831:1835 endo- 1831:1835 endo- 1831:1835 While the tripartite differentiation of the zygospore wall is well established in Zygnematopyhceae, Spirogyra showed cellulose fibrils arranged in a helicoidal pattern in the endo- and exospore. 36561459 9 83 with compounds 1473:1481 arg1 character 1507:1515 a non-hydrolysable character 1488:1515 a non-hydrolysable character 1488:1515 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 3 84 theme cell 545:548 arg1 walls 550:554 unique multi-layered cell walls 524:554 unique multi-layered cell walls 524:554 Sexual reproduction occurs in Zygnematophyceae by conjugation and results in the formation of zygospores, possessing unique multi-layered cell walls, which might have been crucial in terrestrialization. 36561459 12 85 theme complex 2105:2111 arg1 structure 2122:2130 a highly complex internal structure 2096:2130 a highly complex internal structure as well as aromatics 2096:2151 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 5 86 theme atomic 947:952 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 86 theme atomic 947:952 arg1 microscopy 960:969 atomic force microscopy 947:969 atomic force microscopy 947:969 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 10 87 theme tripartite 1666:1675 arg1 differentiation 1677:1691 the tripartite differentiation 1662:1691 the tripartite differentiation of the zygospore wall 1662:1713 While the tripartite differentiation of the zygospore wall is well established in Zygnematopyhceae, Spirogyra showed cellulose fibrils arranged in a helicoidal pattern in the endo- and exospore. 36561459 3 88 theme unique 524:529 arg1 walls 550:554 unique multi-layered cell walls 524:554 unique multi-layered cell walls 524:554 Sexual reproduction occurs in Zygnematophyceae by conjugation and results in the formation of zygospores, possessing unique multi-layered cell walls, which might have been crucial in terrestrialization. 36561459 5 89 theme fixation/freeze 894:908 arg1 substitution 910:921 high pressure freeze fixation/freeze substitution 873:921 high pressure freeze fixation/freeze substitution 873:921 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 13 90 theme components 2342:2351 arg1 integration 2310:2320 the integration 2306:2320 the integration of highly resistant components in the cell wall 2306:2368 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 13 90 theme components 2342:2351 arg1 arrangement 2274:2284 the newly discovered special three-dimensional arrangement 2227:2284 the newly discovered special three-dimensional arrangement of microfibrils 2227:2300 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 7 91 theme aromatic 1287:1294 arg1 compounds 1296:1304 aromatic compounds 1287:1304 aromatic compounds 1287:1304 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 14 92 theme zygospore 2475:2483 arg1 wall 2490:2493 the intricate zygospore cell wall 2461:2493 the intricate zygospore cell wall 2461:2493 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 12 93 theme zygospores 2077:2086 arg1 wall 2049:2052 the cell wall 2040:2052 the cell wall of the sexually formed zygospores 2040:2086 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 6 94 theme organization 1041:1052 arg1 detection 1012:1020 the detection 1008:1020 the detection of the subcellular organization 1008:1052 This comprehensive analysis allowed the detection of the subcellular organization and showed three main layers of the zygospore wall, termed endo-, meso- and exospore. 36561459 4 95 theme sampled 674:680 arg1 sp 692:693 field sampled Spirogyra sp 668:693 field sampled Spirogyra sp 668:693 We investigated the structure and chemical composition of field sampled Spirogyra sp. 36561459 7 96 dep composed 1167:1174 arg1 whereas 1238:1244 whereas 1238:1244 whereas 1238:1244 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 5 97 theme multiple 720:727 arg1 techniques 764:773 multiple microscopical and spectral imaging techniques 720:773 multiple microscopical and spectral imaging techniques 720:773 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 98 theme Raman 924:928 arg1 spectroscopy 930:941 Raman spectroscopy 924:941 Raman spectroscopy 924:941 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 98 theme Raman 924:928 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 99 theme pressure 878:885 arg1 substitution 910:921 high pressure freeze fixation/freeze substitution 873:921 high pressure freeze fixation/freeze substitution 873:921 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 10 100 theme zygospore 1700:1708 arg1 wall 1710:1713 the zygospore wall 1696:1713 the zygospore wall 1696:1713 While the tripartite differentiation of the zygospore wall is well established in Zygnematopyhceae, Spirogyra showed cellulose fibrils arranged in a helicoidal pattern in the endo- and exospore. 36561459 4 101 theme chemical 644:651 arg1 composition 653:663 chemical composition 644:663 chemical composition 644:663 We investigated the structure and chemical composition of field sampled Spirogyra sp. 36561459 1 102 from aquatic 200:206 arg1 live 192:195 live 192:195 live 192:195 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 13 103 theme special 2248:2254 arg1 arrangement 2274:2284 the newly discovered special three-dimensional arrangement 2227:2284 the newly discovered special three-dimensional arrangement of microfibrils 2227:2300 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 13 104 theme vegetative 2391:2400 arg1 state 2402:2406 the vegetative state 2387:2406 the vegetative state 2387:2406 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 8 105 theme chemical 1367:1374 arg1 composition 1376:1386 The possible chemical composition 1354:1386 The possible chemical composition 1354:1386 The possible chemical composition remains elusive, but algaenan or a sporopollenin-like material is suggested. 36561459 5 106 theme zygospore 696:704 arg1 microscopy 818:827 confocal laser scanning microscopy 794:827 confocal laser scanning microscopy 794:827 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 106 theme zygospore 696:704 arg1 spectroscopy 930:941 Raman spectroscopy 924:941 Raman spectroscopy 924:941 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 106 theme zygospore 696:704 arg1 microscopy 782:791 light microscopy 776:791 light microscopy 776:791 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 106 theme zygospore 696:704 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 106 theme zygospore 696:704 arg1 microscopy 852:861 transmission electron microscopy 830:861 transmission electron microscopy following high pressure freeze fixation/freeze substitution 830:921 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 106 theme zygospore 696:704 arg1 microscopy 960:969 atomic force microscopy 947:969 atomic force microscopy 947:969 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 0 107 theme Spirogyra 29:37 arg1 Zygospores 0:9 Zygospores 0:9 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 0:89 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 36561459 6 108 theme zygospore 1090:1098 arg1 wall 1100:1103 the zygospore wall 1086:1103 the zygospore wall 1086:1103 This comprehensive analysis allowed the detection of the subcellular organization and showed three main layers of the zygospore wall, termed endo-, meso- and exospore. 36561459 0 109 from imaging 82:88 arg1 insights 44:51 new insights 40:51 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 0:89 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 36561459 14 110 theme comprehensive 2439:2451 arg1 view 2453:2456 a comprehensive view 2437:2456 a comprehensive view on the intricate zygospore cell wall 2437:2493 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 11 111 theme lipid 1876:1880 arg1 bodies 1882:1887 lipid bodies 1876:1887 lipid bodies 1876:1887 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 1 112 theme streptophyte 120:131 arg1 Embryophytes 178:189 Embryophytes 178:189 Embryophytes 178:189 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 1 112 theme streptophyte 120:131 arg1 algae 139:143 streptophyte green algae 120:143 streptophyte green algae 120:143 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 4 113 theme sp 692:693 arg1 structure 630:638 structure 630:638 structure 630:638 We investigated the structure and chemical composition of field sampled Spirogyra sp. 36561459 4 113 theme sp 692:693 arg1 composition 653:663 chemical composition 644:663 chemical composition 644:663 We investigated the structure and chemical composition of field sampled Spirogyra sp. 36561459 5 114 theme spectral 747:754 arg1 techniques 764:773 multiple microscopical and spectral imaging techniques 720:773 multiple microscopical and spectral imaging techniques 720:773 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 11 115 theme zygospore 1981:1989 arg1 synthesis 1996:2004 zygospore wall synthesis 1981:2004 zygospore wall synthesis 1981:2004 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 1 116 theme algae 139:143 arg1 class 111:115 a class 109:115 a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats 109:235 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 1 116 theme algae 139:143 arg1 Zygnematophyceae 91:106 Zygnematophyceae 91:106 Zygnematophyceae 91:106 Zygnematophyceae, a class of streptophyte green algae and sister group to land plants (Embryophytes) live in aquatic to semi-terrestrial habitats. 36561459 6 117 theme main 1071:1074 arg1 layers 1076:1081 three main layers 1065:1081 three main layers of the zygospore wall, termed endo-, meso- and exospore 1065:1137 This comprehensive analysis allowed the detection of the subcellular organization and showed three main layers of the zygospore wall, termed endo-, meso- and exospore. 36561459 3 118 contain possessing 513:522 arg1 zygospores 501:510 zygospores 501:510 zygospores 501:510 Sexual reproduction occurs in Zygnematophyceae by conjugation and results in the formation of zygospores, possessing unique multi-layered cell walls, which might have been crucial in terrestrialization. 36561459 3 118 contain possessing 513:522 arg2 walls 550:554 unique multi-layered cell walls 524:554 unique multi-layered cell walls 524:554 Sexual reproduction occurs in Zygnematophyceae by conjugation and results in the formation of zygospores, possessing unique multi-layered cell walls, which might have been crucial in terrestrialization. 36561459 2 119 dep aquatic 258:264 arg1 to 266:267 to 266:267 to 266:267 The transition from aquatic to terrestrial environments requires adaptations in the physiology of vegetative cells and in the structural properties of their cell walls. 36561459 2 119 dep aquatic 258:264 arg1 terrestrial 269:279 terrestrial 269:279 terrestrial 269:279 The transition from aquatic to terrestrial environments requires adaptations in the physiology of vegetative cells and in the structural properties of their cell walls. 36561459 11 120 theme zygospore 1902:1910 arg1 formation 1917:1925 early zygospore wall formation 1896:1925 early zygospore wall formation 1896:1925 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 7 121 theme middle 1265:1270 arg1 layer 1272:1276 the electron dense middle layer 1246:1276 the electron dense middle layer 1246:1276 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 9 122 theme high 1638:1641 arg1 irradiation 1643:1653 high irradiation 1638:1653 high irradiation 1638:1653 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 10 123 dep endo- 1831:1835 arg1 the 1827:1829 the 1827:1829 the 1827:1829 While the tripartite differentiation of the zygospore wall is well established in Zygnematopyhceae, Spirogyra showed cellulose fibrils arranged in a helicoidal pattern in the endo- and exospore. 36561459 14 124 from view 2453:2456 arg1 wall 2490:2493 the intricate zygospore cell wall 2461:2493 the intricate zygospore cell wall 2461:2493 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 5 125 theme imaging 756:762 arg1 techniques 764:773 multiple microscopical and spectral imaging techniques 720:773 multiple microscopical and spectral imaging techniques 720:773 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 12 126 theme Multimodal 2007:2016 arg1 imaging 2018:2024 Multimodal imaging 2007:2024 Multimodal imaging 2007:2024 Multimodal imaging revealed that the cell wall of the sexually formed zygospores possess a highly complex internal structure as well as aromatics, likely acting as protective compounds and leading to impregnation. 36561459 9 127 theme higher 1559:1564 arg1 plants 1566:1571 higher plants 1559:1571 higher plants 1559:1571 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 7 128 theme electron 1250:1257 arg1 layer 1272:1276 the electron dense middle layer 1246:1276 the electron dense middle layer 1246:1276 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 0 129 theme green 18:22 arg1 Spirogyra 29:37 the green alga Spirogyra 14:37 the green alga Spirogyra 14:37 Zygospores of the green alga Spirogyra: new insights from structural and chemical imaging. 36561459 13 130 theme cell 2360:2363 arg1 wall 2365:2368 the cell wall 2356:2368 the cell wall 2356:2368 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 2 131 theme walls 400:404 arg1 properties 375:384 the structural properties 360:384 the structural properties of their cell walls 360:404 The transition from aquatic to terrestrial environments requires adaptations in the physiology of vegetative cells and in the structural properties of their cell walls. 36561459 7 132 theme different 1200:1208 arg1 appearance 1226:1235 different ultrastructural appearance 1200:1235 different ultrastructural appearance 1200:1235 The endo- and exospore are composed of polysaccharides with different ultrastructural appearance, whereas the electron dense middle layer contains aromatic compounds as further characterized by Raman spectroscopy. 36561459 9 133 theme plants 1566:1571 arg1 pollen 1549:1554 pollen 1549:1554 pollen 1549:1554 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 9 133 theme plants 1566:1571 arg1 spores 1538:1543 moss spores 1533:1543 moss spores 1533:1543 Similar compounds with a non-hydrolysable character can be found in moss spores and pollen of higher plants, suggesting a protective function against desiccation stress and high irradiation. 36561459 13 134 from arrangement 2274:2284 arg1 wall 2365:2368 the cell wall 2356:2368 the cell wall 2356:2368 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 14 135 theme plant 2558:2562 arg1 evolution 2564:2572 plant evolution 2558:2572 plant evolution 2558:2572 The variety of methods gave a comprehensive view on the intricate zygospore cell wall and its potential key role in the terrestrial colonization and plant evolution is discussed. 36561459 5 136 theme scanning 809:816 arg1 microscopy 818:827 confocal laser scanning microscopy 794:827 confocal laser scanning microscopy 794:827 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 5 136 theme scanning 809:816 arg1 walls 711:715 zygospore cell walls 696:715 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 696:970 zygospore cell walls by multiple microscopical and spectral imaging techniques: light microscopy, confocal laser scanning microscopy, transmission electron microscopy following high pressure freeze fixation/freeze substitution, Raman spectroscopy and atomic force microscopy. 36561459 13 137 theme resistant 2332:2340 arg1 components 2342:2351 highly resistant components 2325:2351 highly resistant components in the cell wall 2325:2368 Both, the newly discovered special three-dimensional arrangement of microfibrils and the integration of highly resistant components in the cell wall are not found in the vegetative state. 36561459 11 138 theme lipids 1971:1976 arg1 role 1963:1966 a key role 1957:1966 a key role of lipids in zygospore wall synthesis 1957:2004 Initial incorporation of lipid bodies during early zygospore wall formation was also observed, suggesting a key role of lipids in zygospore wall synthesis. 36561459 10 139 theme helicoidal 1805:1814 arg1 pattern 1816:1822 a helicoidal pattern 1803:1822 a helicoidal pattern in the endo- and exospore 1803:1848 While the tripartite differentiation of the zygospore wall is well established in Zygnematopyhceae, Spirogyra showed cellulose fibrils arranged in a helicoidal pattern in the endo- and exospore. 36647045 0 0 theme alveolar 125:132 arg1 cells 142:146 hyperoxia-injured alveolar type II cells 107:146 hyperoxia-injured alveolar type II cells 107:146 O-linked N-acetylglucosamine affects mitochondrial homeostasis by regulating Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury. 36647045 1 1 theme bronchopulmonary 352:367 arg1 dysplasia 369:377 bronchopulmonary dysplasia 352:377 bronchopulmonary dysplasia (BPD) 352:383 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 1 1 theme bronchopulmonary 352:367 arg1 BPD 380:382 BPD 380:382 BPD 380:382 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 5 2 theme Parkin 1064:1069 arg1 binding 1053:1059 the binding 1049:1059 the binding of Parkin and O-GlcNAc 1049:1082 We constructed rat Park2 overexpression and knockdown plasmmids for in vitro verification and Co-immunoprecipitation corroborated the binding of Parkin and O-GlcNAc. 36647045 1 3 theme N-acetylglucosamine 187:205 arg1 sensor 242:247 a sensor 240:247 a sensor of cell state 240:261 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 1 3 theme N-acetylglucosamine 187:205 arg1 level 171:175 The level 167:175 The level of linked N-acetylglucosamine (O-GlcNAc) 167:216 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 3 4 theme OGT 651:653 arg1 inhibitor 624:632 an OGA inhibitor 617:632 an OGA inhibitor 617:632 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 3 4 theme OGT 651:653 arg1 inhibitor 655:663 an OGT inhibitor 648:663 an OGT inhibitor 648:663 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 5 5 dep in 987:988 arg1 vitro 990:994 vitro 990:994 vitro 990:994 We constructed rat Park2 overexpression and knockdown plasmmids for in vitro verification and Co-immunoprecipitation corroborated the binding of Parkin and O-GlcNAc. 36647045 0 6 theme hyperoxia-injured 107:123 arg1 cells 142:146 hyperoxia-injured alveolar type II cells 107:146 hyperoxia-injured alveolar type II cells 107:146 O-linked N-acetylglucosamine affects mitochondrial homeostasis by regulating Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury. 36647045 4 7 theme cell 766:769 arg1 viability 771:779 cell viability 766:779 cell viability 766:779 The metabolic rerouting, cell viability and apoptosis resulting from the changes in O-GlcNAc glycosyltransferase levels were evaluated in RLE-6TN cells after hyperoxia exposure. 36647045 10 8 theme increased 1649:1657 arg1 O-GlcNAcylation 1659:1673 increased O-GlcNAcylation 1649:1673 increased O-GlcNAcylation of Parkin 1649:1683 CONCLUSION The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys. 36647045 10 9 theme hyperoxia-induced 1697:1713 arg1 injurys 1738:1744 hyperoxia-induced alveolar type II cells injurys 1697:1744 hyperoxia-induced alveolar type II cells injurys 1697:1744 CONCLUSION The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys. 36647045 6 10 with rats 1146:1149 arg1 TG 1156:1157 TG 1156:1157 TG 1156:1157 Finally, we assessed morphological detection in neonatal BPD rats with TG and OS treatment. 36647045 6 10 with rats 1146:1149 arg1 OS 1163:1164 OS 1163:1164 OS 1163:1164 Finally, we assessed morphological detection in neonatal BPD rats with TG and OS treatment. 36647045 0 11 theme II 139:140 arg1 cells 142:146 hyperoxia-injured alveolar type II cells 107:146 hyperoxia-injured alveolar type II cells 107:146 O-linked N-acetylglucosamine affects mitochondrial homeostasis by regulating Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury. 36647045 8 12 theme hyperoxia-induced 1359:1375 arg1 injury 1398:1403 hyperoxia-induced lung epithelial cell injury 1359:1403 hyperoxia-induced lung epithelial cell injury 1359:1403 However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. 36647045 6 13 theme BPD 1142:1144 arg1 rats 1146:1149 neonatal BPD rats 1133:1149 neonatal BPD rats with TG and OS treatment 1133:1174 Finally, we assessed morphological detection in neonatal BPD rats with TG and OS treatment. 36647045 3 14 dep inhibitor 624:632 arg1 OS 643:644 OS 643:644 OS 643:644 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 3 14 dep inhibitor 624:632 arg1 OSMI-1 635:640 OSMI-1 635:640 OSMI-1 (OS) 635:645 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 0 15 theme type 134:137 arg1 cells 142:146 hyperoxia-injured alveolar type II cells 107:146 hyperoxia-injured alveolar type II cells 107:146 O-linked N-acetylglucosamine affects mitochondrial homeostasis by regulating Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury. 36647045 1 16 dep cells 335:339 arg1 injure 341:346 injure 341:346 injure 341:346 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 6 17 theme neonatal 1133:1140 arg1 rats 1146:1149 neonatal BPD rats 1133:1149 neonatal BPD rats with TG and OS treatment 1133:1174 Finally, we assessed morphological detection in neonatal BPD rats with TG and OS treatment. 36647045 6 18 dep TG 1156:1157 arg1 treatment 1166:1174 treatment 1166:1174 treatment 1166:1174 Finally, we assessed morphological detection in neonatal BPD rats with TG and OS treatment. 36647045 4 19 theme RLE-6TN 879:885 arg1 cells 887:891 RLE-6TN cells 879:891 RLE-6TN cells 879:891 The metabolic rerouting, cell viability and apoptosis resulting from the changes in O-GlcNAc glycosyltransferase levels were evaluated in RLE-6TN cells after hyperoxia exposure. 36647045 4 20 theme metabolic 745:753 arg1 rerouting 755:763 The metabolic rerouting 741:763 The metabolic rerouting 741:763 The metabolic rerouting, cell viability and apoptosis resulting from the changes in O-GlcNAc glycosyltransferase levels were evaluated in RLE-6TN cells after hyperoxia exposure. 36647045 0 21 link O-linked 0:7 arg1 N-acetylglucosamine 9:27 O-linked N-acetylglucosamine 0:27 O-linked N-acetylglucosamine 0:27 O-linked N-acetylglucosamine affects mitochondrial homeostasis by regulating Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury. 36647045 9 22 theme Mitochondrial 1505:1517 arg1 homeostasis 1519:1529 Mitochondrial homeostasis 1505:1529 Mitochondrial homeostasis 1505:1529 Mitochondrial homeostasis was affected by O-GlcNAc and regulated Parkin. 36647045 6 23 from detection 1120:1128 arg1 rats 1146:1149 neonatal BPD rats 1133:1149 neonatal BPD rats with TG and OS treatment 1133:1174 Finally, we assessed morphological detection in neonatal BPD rats with TG and OS treatment. 36647045 7 24 theme RLE-6TN 1264:1270 arg1 cells 1272:1276 RLE-6TN cells 1264:1276 RLE-6TN cells 1264:1276 RESULTS We found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia. 36647045 8 25 theme cell 1485:1488 arg1 proliferation 1490:1502 the cell proliferation 1481:1502 the cell proliferation 1481:1502 However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. 36647045 5 26 theme O-GlcNAc 1075:1082 arg1 binding 1053:1059 the binding 1049:1059 the binding of Parkin and O-GlcNAc 1049:1082 We constructed rat Park2 overexpression and knockdown plasmmids for in vitro verification and Co-immunoprecipitation corroborated the binding of Parkin and O-GlcNAc. 36647045 1 27 dep BACKGROUND 156:165 arg1 clarified 398:406 clarified 398:406 has not been clarified 385:406 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 1 27 dep BACKGROUND 156:165 arg1 proved 227:232 proved 227:232 has been proved to be a sensor of cell state 218:261 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 10 28 theme decreased 1619:1627 arg1 levels 1638:1643 the decreased O-GlcNAc levels 1615:1643 the decreased O-GlcNAc levels 1615:1643 CONCLUSION The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys. 36647045 4 29 theme hyperoxia 899:907 arg1 exposure 909:916 hyperoxia exposure 899:916 hyperoxia exposure 899:916 The metabolic rerouting, cell viability and apoptosis resulting from the changes in O-GlcNAc glycosyltransferase levels were evaluated in RLE-6TN cells after hyperoxia exposure. 36647045 6 30 theme morphological 1106:1118 arg1 detection 1120:1128 morphological detection 1106:1128 morphological detection in neonatal BPD rats with TG and OS treatment 1106:1174 Finally, we assessed morphological detection in neonatal BPD rats with TG and OS treatment. 36647045 7 31 theme O-GlcNAc 1208:1215 arg1 content 1217:1223 O-GlcNAc content 1208:1223 O-GlcNAc content 1208:1223 RESULTS We found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia. 36647045 7 32 theme enzymes 1253:1259 arg1 levels 1229:1234 levels 1229:1234 levels of its metabolic enzymes 1229:1259 RESULTS We found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia. 36647045 7 32 theme enzymes 1253:1259 arg1 decrease 1196:1203 a decrease 1194:1203 a decrease in O-GlcNAc content 1194:1223 RESULTS We found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia. 36647045 0 33 theme O-linked 0:7 arg1 N-acetylglucosamine 9:27 O-linked N-acetylglucosamine 0:27 O-linked N-acetylglucosamine 0:27 O-linked N-acetylglucosamine affects mitochondrial homeostasis by regulating Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury. 36647045 10 34 dep CONCLUSION 1578:1587 arg1 revealed 1601:1608 revealed 1601:1608 revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys 1601:1744 CONCLUSION The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys. 36647045 7 35 dep RESULTS 1177:1183 arg1 found 1188:1192 found 1188:1192 found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia 1188:1292 RESULTS We found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia. 36647045 8 36 theme cell 1393:1396 arg1 injury 1398:1403 hyperoxia-induced lung epithelial cell injury 1359:1403 hyperoxia-induced lung epithelial cell injury 1359:1403 However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. 36647045 0 37 theme mitochondrial 37:49 arg1 homeostasis 51:61 mitochondrial homeostasis 37:61 mitochondrial homeostasis 37:61 O-linked N-acetylglucosamine affects mitochondrial homeostasis by regulating Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury. 36647045 1 38 theme hyperoxia-induced 290:306 arg1 cells 335:339 hyperoxia-induced alveolar type 2 epithelial cells 290:339 hyperoxia-induced alveolar type 2 epithelial cells injure 290:346 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 4 39 theme O-GlcNAc 825:832 arg1 levels 854:859 O-GlcNAc glycosyltransferase levels 825:859 O-GlcNAc glycosyltransferase levels 825:859 The metabolic rerouting, cell viability and apoptosis resulting from the changes in O-GlcNAc glycosyltransferase levels were evaluated in RLE-6TN cells after hyperoxia exposure. 36647045 7 40 from decrease 1196:1203 arg1 content 1217:1223 O-GlcNAc content 1208:1223 O-GlcNAc content 1208:1223 RESULTS We found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia. 36647045 3 41 theme 85 563:564 arg1 % 565:565 % 565:565 % 565:565 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 8 42 theme function 1326:1333 arg1 inhibition 1308:1317 the inhibition 1304:1317 the inhibition of OGT function with OSMI-1 1304:1345 However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. 36647045 1 43 theme alveolar 308:315 arg1 cells 335:339 hyperoxia-induced alveolar type 2 epithelial cells 290:339 hyperoxia-induced alveolar type 2 epithelial cells injure 290:346 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 10 44 theme cells 1732:1736 arg1 injurys 1738:1744 hyperoxia-induced alveolar type II cells injurys 1697:1744 hyperoxia-induced alveolar type II cells injurys 1697:1744 CONCLUSION The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys. 36647045 3 45 theme % 565:565 arg1 hyperoxia 567:575 85% hyperoxia 563:575 85% hyperoxia for 0, 24 and 48 h 563:594 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 7 46 theme metabolic 1243:1251 arg1 enzymes 1253:1259 its metabolic enzymes 1239:1259 its metabolic enzymes 1239:1259 RESULTS We found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia. 36647045 2 47 theme functional 472:481 arg1 damage 483:488 functional damage 472:488 functional damage in hyperoxia-induced alveolar cells 472:524 In this study, we evaluated if these effects ultimately led to functional damage in hyperoxia-induced alveolar cells. 36647045 1 48 theme type 317:320 arg1 cells 335:339 hyperoxia-induced alveolar type 2 epithelial cells 290:339 hyperoxia-induced alveolar type 2 epithelial cells injure 290:346 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 2 49 from damage 483:488 arg1 cells 520:524 hyperoxia-induced alveolar cells 493:524 hyperoxia-induced alveolar cells 493:524 In this study, we evaluated if these effects ultimately led to functional damage in hyperoxia-induced alveolar cells. 36647045 5 50 theme Park2 938:942 arg1 overexpression 944:957 rat Park2 overexpression 934:957 rat Park2 overexpression 934:957 We constructed rat Park2 overexpression and knockdown plasmmids for in vitro verification and Co-immunoprecipitation corroborated the binding of Parkin and O-GlcNAc. 36647045 10 51 theme type 1724:1727 arg1 injurys 1738:1744 hyperoxia-induced alveolar type II cells injurys 1697:1744 hyperoxia-induced alveolar type II cells injurys 1697:1744 CONCLUSION The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys. 36647045 10 52 theme O-GlcNAc 1629:1636 arg1 levels 1638:1643 the decreased O-GlcNAc levels 1615:1643 the decreased O-GlcNAc levels 1615:1643 CONCLUSION The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys. 36647045 1 53 link linked 180:185 arg1 O-GlcNAc 208:215 O-GlcNAc 208:215 O-GlcNAc 208:215 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 1 53 link linked 180:185 arg1 N-acetylglucosamine 187:205 linked N-acetylglucosamine 180:205 linked N-acetylglucosamine (O-GlcNAc) 180:216 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 8 54 theme OGT 1322:1324 arg1 function 1326:1333 OGT function 1322:1333 OGT function 1322:1333 However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. 36647045 7 55 from levels 1229:1234 arg1 content 1217:1223 O-GlcNAc content 1208:1223 O-GlcNAc content 1208:1223 RESULTS We found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia. 36647045 0 56 theme Parkin-dependent 77:92 arg1 injury 148:153 Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury 77:153 Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury 77:153 O-linked N-acetylglucosamine affects mitochondrial homeostasis by regulating Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury. 36647045 1 57 theme epithelial 324:333 arg1 cells 335:339 hyperoxia-induced alveolar type 2 epithelial cells 290:339 hyperoxia-induced alveolar type 2 epithelial cells injure 290:346 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 8 58 with inhibition 1308:1317 arg1 OSMI-1 1340:1345 OSMI-1 1340:1345 OSMI-1 1340:1345 However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. 36647045 0 59 from mitophagy 94:102 arg1 cells 142:146 hyperoxia-injured alveolar type II cells 107:146 hyperoxia-injured alveolar type II cells 107:146 O-linked N-acetylglucosamine affects mitochondrial homeostasis by regulating Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury. 36647045 1 60 with relationship 272:283 arg1 cells 335:339 hyperoxia-induced alveolar type 2 epithelial cells 290:339 hyperoxia-induced alveolar type 2 epithelial cells injure 290:346 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 4 61 theme glycosyltransferase 834:852 arg1 levels 854:859 O-GlcNAc glycosyltransferase levels 825:859 O-GlcNAc glycosyltransferase levels 825:859 The metabolic rerouting, cell viability and apoptosis resulting from the changes in O-GlcNAc glycosyltransferase levels were evaluated in RLE-6TN cells after hyperoxia exposure. 36647045 4 62 from changes 814:820 arg1 levels 854:859 O-GlcNAc glycosyltransferase levels 825:859 O-GlcNAc glycosyltransferase levels 825:859 The metabolic rerouting, cell viability and apoptosis resulting from the changes in O-GlcNAc glycosyltransferase levels were evaluated in RLE-6TN cells after hyperoxia exposure. 36647045 5 63 theme knockdown 963:971 arg1 plasmmids 973:981 knockdown plasmmids 963:981 knockdown plasmmids for in vitro verification and Co-immunoprecipitation 963:1034 We constructed rat Park2 overexpression and knockdown plasmmids for in vitro verification and Co-immunoprecipitation corroborated the binding of Parkin and O-GlcNAc. 36647045 8 64 theme lung 1377:1380 arg1 injury 1398:1403 hyperoxia-induced lung epithelial cell injury 1359:1403 hyperoxia-induced lung epithelial cell injury 1359:1403 However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. 36647045 8 65 theme cell 1415:1418 arg1 metabolism 1420:1429 cell metabolism 1415:1429 cell metabolism 1415:1429 However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. 36647045 3 66 theme Thiamet 601:607 arg1 inhibitor 624:632 an OGA inhibitor 617:632 an OGA inhibitor 617:632 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 3 66 theme Thiamet 601:607 arg1 TG 612:613 TG 612:613 TG 612:613 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 3 66 theme Thiamet 601:607 arg1 G 609:609 Thiamet G 601:609 Thiamet G (TG) 601:614 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 9 67 theme regulated 1560:1568 arg1 Parkin 1570:1575 regulated Parkin 1560:1575 regulated Parkin 1560:1575 Mitochondrial homeostasis was affected by O-GlcNAc and regulated Parkin. 36647045 10 68 theme Parkin 1678:1683 arg1 levels 1638:1643 the decreased O-GlcNAc levels 1615:1643 the decreased O-GlcNAc levels 1615:1643 CONCLUSION The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys. 36647045 10 68 theme Parkin 1678:1683 arg1 O-GlcNAcylation 1659:1673 increased O-GlcNAcylation 1649:1673 increased O-GlcNAcylation of Parkin 1649:1683 CONCLUSION The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys. 36647045 3 69 dep METHODS 527:533 arg1 treated 538:544 treated 538:544 treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor 538:738 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 3 70 theme RLE-6TN 546:552 arg1 cells 554:558 RLE-6TN cells 546:558 RLE-6TN cells 546:558 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 5 71 theme in 987:988 arg1 verification 996:1007 in vitro verification 987:1007 in vitro verification 987:1007 We constructed rat Park2 overexpression and knockdown plasmmids for in vitro verification and Co-immunoprecipitation corroborated the binding of Parkin and O-GlcNAc. 36647045 2 72 theme hyperoxia-induced 493:509 arg1 cells 520:524 hyperoxia-induced alveolar cells 493:524 hyperoxia-induced alveolar cells 493:524 In this study, we evaluated if these effects ultimately led to functional damage in hyperoxia-induced alveolar cells. 36647045 3 73 theme O-GlcNAc 720:727 arg1 synthesis 707:715 synthesis 707:715 synthesis of O-GlcNAc as a donor 707:738 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 2 74 theme alveolar 511:518 arg1 cells 520:524 hyperoxia-induced alveolar cells 493:524 hyperoxia-induced alveolar cells 493:524 In this study, we evaluated if these effects ultimately led to functional damage in hyperoxia-induced alveolar cells. 36647045 3 75 theme OGA 620:622 arg1 G 609:609 Thiamet G 601:609 Thiamet G (TG) 601:614 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 3 75 theme OGA 620:622 arg1 inhibitor 624:632 an OGA inhibitor 617:632 an OGA inhibitor 617:632 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 3 75 theme OGA 620:622 arg1 inhibitor 655:663 an OGT inhibitor 648:663 an OGT inhibitor 648:663 METHODS We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. 36647045 8 76 theme epithelial 1382:1391 arg1 injury 1398:1403 hyperoxia-induced lung epithelial cell injury 1359:1403 hyperoxia-induced lung epithelial cell injury 1359:1403 However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. 36647045 10 77 theme alveolar 1715:1722 arg1 injurys 1738:1744 hyperoxia-induced alveolar type II cells injurys 1697:1744 hyperoxia-induced alveolar type II cells injurys 1697:1744 CONCLUSION The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys. 36647045 1 78 theme cell 252:255 arg1 state 257:261 cell state 252:261 cell state 252:261 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 0 79 theme mitophagy 94:102 arg1 injury 148:153 Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury 77:153 Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury 77:153 O-linked N-acetylglucosamine affects mitochondrial homeostasis by regulating Parkin-dependent mitophagy in hyperoxia-injured alveolar type II cells injury. 36647045 5 80 theme rat 934:936 arg1 overexpression 944:957 rat Park2 overexpression 934:957 rat Park2 overexpression 934:957 We constructed rat Park2 overexpression and knockdown plasmmids for in vitro verification and Co-immunoprecipitation corroborated the binding of Parkin and O-GlcNAc. 36647045 1 81 theme linked 180:185 arg1 O-GlcNAc 208:215 O-GlcNAc 208:215 O-GlcNAc 208:215 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 1 81 theme linked 180:185 arg1 N-acetylglucosamine 187:205 linked N-acetylglucosamine 180:205 linked N-acetylglucosamine (O-GlcNAc) 180:216 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 1 82 with dysplasia 369:377 arg1 cells 335:339 hyperoxia-induced alveolar type 2 epithelial cells 290:339 hyperoxia-induced alveolar type 2 epithelial cells injure 290:346 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 1 83 theme state 257:261 arg1 sensor 242:247 a sensor 240:247 a sensor of cell state 240:261 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36647045 1 83 theme state 257:261 arg1 level 171:175 The level 167:175 The level of linked N-acetylglucosamine (O-GlcNAc) 167:216 BACKGROUND The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. 36422339 11 0 theme colonization 2177:2188 arg1 pattern 2156:2162 the pattern 2152:2162 the pattern of microbial colonization 2152:2188 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 3 1 theme profound 450:457 arg1 effects 459:465 profound effects 450:465 profound effects 450:465 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 4 2 from content 602:608 arg1 silages 640:646 corn silages 635:646 corn silages 635:646 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 7 3 theme corn 1240:1243 arg1 silages 1245:1251 corn silages 1240:1251 corn silages 1240:1251 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 11 4 theme cell 2105:2108 arg1 walls 2110:2114 plant cell walls 2099:2114 plant cell walls 2099:2114 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 6 5 theme silage 993:998 arg1 digestibility 1000:1012 Corn silage digestibility 988:1012 Corn silage digestibility 988:1012 Corn silage digestibility was assessed by in situ degradation methods. 36422339 10 6 theme ether-linked 1954:1965 arg1 content 1970:1976 the ether-linked FA content 1950:1976 the ether-linked FA content 1950:1976 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 4 7 theme phenolic 588:595 arg1 content 602:608 bound phenolic acid content 582:608 bound phenolic acid content 582:608 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 3 8 theme digestion 504:512 arg1 rate 474:477 rate 474:477 rate 474:477 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 3 8 theme digestion 504:512 arg1 extent 487:492 the extent 483:492 the extent 483:492 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 5 9 theme corn 793:796 arg1 silages 798:804 eight representative corn silages 772:804 eight representative corn silages with different FA and pCA contents 772:839 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 0 10 theme Acid 121:124 arg1 Contents 126:133 Ferulic and p-Coumaric Acid Contents 98:133 Ferulic and p-Coumaric Acid Contents 98:133 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 5 11 theme rumen 746:750 arg1 method 764:769 an in situ rumen degradation method 735:769 an in situ rumen degradation method 735:769 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 5 12 theme pCA 828:830 arg1 contents 832:839 pCA contents 828:839 pCA contents 828:839 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 9 13 link ester-linked 1637:1648 arg1 FA 1650:1651 ester-linked FA 1637:1651 ester-linked FA 1637:1651 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 8 14 theme corn 1567:1570 arg1 silages 1572:1578 the corn silages 1563:1578 the corn silages 1563:1578 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 3 15 dep rate 474:477 arg1 the 470:472 the 470:472 the 470:472 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 7 16 from pCA 1216:1218 arg1 silages 1245:1251 corn silages 1240:1251 corn silages 1240:1251 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 4 17 theme content 602:608 arg1 effect 572:577 the effect 568:577 the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability 568:676 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 4 17 theme content 602:608 arg1 composition 687:697 the composition 683:697 the composition of the attached bacteria 683:722 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 3 18 from digestion 504:512 arg1 rumen 517:521 rumen 517:521 rumen 517:521 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 5 19 theme in 738:739 arg1 method 764:769 an in situ rumen degradation method 735:769 an in situ rumen degradation method 735:769 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 1 20 theme cell 145:148 arg1 wall 150:153 plant cell wall 139:153 plant cell wall 139:153 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 7 21 from ratio 1231:1235 arg1 silages 1245:1251 corn silages 1240:1251 corn silages 1240:1251 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 7 22 theme corn 1396:1399 arg1 silages 1401:1407 corn silages 1396:1407 corn silages 1396:1407 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 3 23 contain have 445:448 arg2 effects 459:465 profound effects 450:465 profound effects 450:465 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 3 23 contain have 445:448 arg1 attachment 381:390 The attachment 377:390 The attachment of rumen microbes to plant cell wall 377:427 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 3 24 from rate 474:477 arg1 rumen 517:521 rumen 517:521 rumen 517:521 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 10 25 theme FA 1896:1897 arg1 content 1899:1905 the initial ether-linked FA content 1871:1905 the initial ether-linked FA content 1871:1905 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 0 26 theme Silages 77:83 arg1 Characteristics 26:40 In Situ Rumen Degradation Characteristics 0:40 In Situ Rumen Degradation Characteristics 0:40 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 0 26 theme Silages 77:83 arg1 Colonization 56:67 Bacterial Colonization 46:67 Bacterial Colonization of Corn Silages 46:83 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 4 27 from composition 687:697 arg1 degradability 664:676 the nutrient degradability 651:676 the nutrient degradability 651:676 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 4 27 from composition 687:697 arg1 silages 640:646 corn silages 635:646 corn silages 635:646 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 3 28 dep digestion 504:512 arg1 forage 497:502 forage 497:502 forage 497:502 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 9 29 link ester-linked 1683:1694 arg1 pCA 1696:1698 ester-linked pCA 1683:1698 ester-linked pCA 1683:1698 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 11 30 theme ether-linked 2068:2079 arg1 acids 2090:2094 ether-linked phenolic acids 2068:2094 ether-linked phenolic acids 2068:2094 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 5 31 with silages 798:804 arg1 FA 821:822 different FA 811:822 different FA 811:822 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 5 31 with silages 798:804 arg1 contents 832:839 pCA contents 828:839 pCA contents 828:839 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 10 32 theme initial 1875:1881 arg1 content 1899:1905 the initial ether-linked FA content 1871:1905 the initial ether-linked FA content 1871:1905 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 9 33 theme h 1590:1590 arg1 fermentation 1598:1609 72 h rumen fermentation 1587:1609 72 h rumen fermentation 1587:1609 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 7 34 theme fibre 1159:1163 arg1 detergent 1149:1157 acid detergent fibre 1144:1163 acid detergent fibre 1144:1163 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 2 35 theme rumen 332:336 arg1 microbes 338:345 rumen microbes 332:345 rumen microbes 332:345 These linkages were deemed to hinder the access of rumen microbes to cell wall polysaccharides. 36422339 0 36 theme In 0:1 arg1 Characteristics 26:40 In Situ Rumen Degradation Characteristics 0:40 In Situ Rumen Degradation Characteristics 0:40 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 7 37 theme acid 1144:1147 arg1 detergent 1149:1157 acid detergent fibre 1144:1163 acid detergent fibre 1144:1163 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 3 38 from rumen 517:521 arg1 rate 474:477 rate 474:477 rate 474:477 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 3 38 from rumen 517:521 arg1 extent 487:492 the extent 483:492 the extent 483:492 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 3 39 theme plant 413:417 arg1 wall 424:427 plant cell wall 413:427 plant cell wall 413:427 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 0 40 theme Rumen 8:12 arg1 Characteristics 26:40 In Situ Rumen Degradation Characteristics 0:40 In Situ Rumen Degradation Characteristics 0:40 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 7 41 theme acids 1332:1336 arg1 composition 1308:1318 the composition 1304:1318 not only the content and but also the composition of phenolic acids 1270:1336 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 7 41 theme acids 1332:1336 arg1 content 1283:1289 the content 1279:1289 not only the content and but also the composition of phenolic acids 1270:1336 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 7 42 from FA 1209:1210 arg1 silages 1245:1251 corn silages 1240:1251 corn silages 1240:1251 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 3 43 theme microbes 401:408 arg1 attachment 381:390 The attachment 377:390 The attachment of rumen microbes to plant cell wall 377:427 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 2 44 theme wall 355:358 arg1 polysaccharides 360:374 cell wall polysaccharides 350:374 cell wall polysaccharides 350:374 These linkages were deemed to hinder the access of rumen microbes to cell wall polysaccharides. 36422339 11 45 theme present 2022:2028 arg1 results 2030:2036 the present results 2018:2036 the present results 2018:2036 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 5 46 theme Holstein 924:931 arg1 cows 933:936 lactating Holstein cows 914:936 lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h 914:971 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 7 47 theme detergent 1123:1131 arg1 related 1181:1187 related 1181:1187 related 1181:1187 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 7 47 theme detergent 1123:1131 arg1 degradability 1086:1098 the effective degradability 1072:1098 the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre 1072:1163 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 9 48 theme ester-linked 1637:1648 arg1 FA 1650:1651 ester-linked FA 1637:1651 ester-linked FA 1637:1651 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 8 49 from phyla 1516:1520 arg1 communities 1539:1549 the bacterial communities 1525:1549 the bacterial communities attached to the corn silages 1525:1578 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 0 50 theme Bacterial 46:54 arg1 Colonization 56:67 Bacterial Colonization 46:67 Bacterial Colonization of Corn Silages 46:83 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 10 51 link ether-linked 1883:1894 arg1 content 1899:1905 the initial ether-linked FA content 1871:1905 the initial ether-linked FA content 1871:1905 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 7 52 theme dry 1103:1105 arg1 matter 1107:1112 dry matter 1103:1112 dry matter 1103:1112 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 11 53 theme profound 2133:2140 arg1 effect 2142:2147 a more profound effect 2126:2147 a more profound effect on the pattern of microbial colonization than the fibre content 2126:2211 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 11 54 theme acids 2090:2094 arg1 content 2057:2063 the content 2053:2063 the content of ether-linked phenolic acids in plant cell walls 2053:2114 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 4 55 theme bacteria 715:722 arg1 effect 572:577 the effect 568:577 the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability 568:676 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 4 55 theme bacteria 715:722 arg1 composition 687:697 the composition 683:697 the composition of the attached bacteria 683:722 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 4 56 from composition 620:630 arg1 silages 640:646 corn silages 635:646 corn silages 635:646 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 5 57 theme matured 906:912 arg1 cows 933:936 lactating Holstein cows 914:936 lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h 914:971 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 11 58 theme microbial 2167:2175 arg1 colonization 2177:2188 microbial colonization 2167:2188 microbial colonization 2167:2188 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 8 59 theme h 1419:1419 arg1 fermentation 1427:1438 24 h rumen fermentation 1416:1438 24 h rumen fermentation 1416:1438 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 10 60 theme correlation 1705:1715 arg1 related 1860:1866 related 1860:1866 related 1860:1866 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 10 60 theme correlation 1705:1715 arg1 analysis 1717:1724 The correlation analysis 1701:1724 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium 1701:1842 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 5 61 dep in 738:739 arg1 situ 741:744 situ 741:744 situ 741:744 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 9 62 theme ester-linked 1683:1694 arg1 pCA 1696:1698 ester-linked pCA 1683:1698 ester-linked pCA 1683:1698 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 11 63 theme plant 2099:2103 arg1 walls 2110:2114 plant cell walls 2099:2114 plant cell walls 2099:2114 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 11 64 link ether-linked 2068:2079 arg1 acids 2090:2094 ether-linked phenolic acids 2068:2094 ether-linked phenolic acids 2068:2094 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 8 65 theme dominant 1507:1514 arg1 Actinobacteria 1453:1466 Actinobacteria 1453:1466 Actinobacteria 1453:1466 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 8 65 theme dominant 1507:1514 arg1 Bacteroidota 1473:1484 Bacteroidota 1473:1484 Bacteroidota 1473:1484 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 8 65 theme dominant 1507:1514 arg1 Firmicutes 1441:1450 Firmicutes 1441:1450 Firmicutes 1441:1450 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 8 65 theme dominant 1507:1514 arg1 phyla 1516:1520 the dominant phyla 1503:1520 the dominant phyla in the bacterial communities attached to the corn silages 1503:1578 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 1 66 theme ferulic 156:162 arg1 FA 170:171 FA 170:171 FA 170:171 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 1 66 theme ferulic 156:162 arg1 acid 164:167 ferulic acid 156:167 ferulic acid (FA) 156:172 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 10 67 theme FA 1967:1968 arg1 content 1970:1976 the ether-linked FA content 1950:1976 the ether-linked FA content 1950:1976 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 4 68 from effect 572:577 arg1 degradability 664:676 the nutrient degradability 651:676 the nutrient degradability 651:676 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 4 68 from effect 572:577 arg1 silages 640:646 corn silages 635:646 corn silages 635:646 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 5 69 theme representative 778:791 arg1 silages 798:804 eight representative corn silages 772:804 eight representative corn silages with different FA and pCA contents 772:839 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 3 70 attach attachment 381:390 arg1 wall 424:427 plant cell wall 413:427 plant cell wall 413:427 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 3 70 attach attachment 381:390 arg2 microbes 401:408 rumen microbes 395:408 rumen microbes 395:408 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 6 71 theme Corn 988:991 arg1 digestibility 1000:1012 Corn silage digestibility 988:1012 Corn silage digestibility 988:1012 Corn silage digestibility was assessed by in situ degradation methods. 36422339 10 72 theme pCA 1995:1997 arg1 content 1970:1976 the ether-linked FA content 1950:1976 the ether-linked FA content 1950:1976 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 10 72 theme pCA 1995:1997 arg1 ratio 1986:1990 the ratio 1982:1990 the ratio of pCA to FA 1982:2003 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 4 73 theme bound 582:586 arg1 content 602:608 bound phenolic acid content 582:608 bound phenolic acid content 582:608 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 8 74 theme bacterial 1529:1537 arg1 communities 1539:1549 the bacterial communities 1525:1549 the bacterial communities attached to the corn silages 1525:1578 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 11 75 from effect 2142:2147 arg1 pattern 2156:2162 the pattern 2152:2162 the pattern of microbial colonization 2152:2188 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 10 76 link ether-linked 1954:1965 arg1 content 1970:1976 the ether-linked FA content 1950:1976 the ether-linked FA content 1950:1976 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 5 77 theme degradation 752:762 arg1 method 764:769 an in situ rumen degradation method 735:769 an in situ rumen degradation method 735:769 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 7 78 theme ether-linked 1196:1207 arg1 FA 1209:1210 the ether-linked FA 1192:1210 the ether-linked FA 1192:1210 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 6 79 dep in 1030:1031 arg1 situ 1033:1036 situ 1033:1036 situ 1033:1036 Corn silage digestibility was assessed by in situ degradation methods. 36422339 3 80 from extent 487:492 arg1 rumen 517:521 rumen 517:521 rumen 517:521 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 1 81 attach linked 213:218 arg2 acid 189:192 p-coumaric acid 178:192 p-coumaric acid (pCA) 178:198 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 1 81 attach linked 213:218 arg2 pCA 195:197 pCA 195:197 pCA 195:197 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 1 81 attach linked 213:218 arg2 FA 170:171 FA 170:171 FA 170:171 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 1 81 attach linked 213:218 arg2 acid 164:167 ferulic acid 156:167 ferulic acid (FA) 156:172 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 1 81 attach linked 213:218 arg3 wall 150:153 plant cell wall 139:153 plant cell wall 139:153 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 7 82 theme silages 1401:1407 arg1 characteristics 1377:1391 the degradation characteristics 1361:1391 the degradation characteristics of corn silages 1361:1407 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 6 83 theme degradation 1038:1048 arg1 methods 1050:1056 in situ degradation methods 1030:1056 in situ degradation methods 1030:1056 Corn silage digestibility was assessed by in situ degradation methods. 36422339 4 84 theme corn 635:638 arg1 silages 640:646 corn silages 635:646 corn silages 635:646 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 0 85 theme Corn 72:75 arg1 Silages 77:83 Corn Silages 72:83 Corn Silages 72:83 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 1 86 theme plant 139:143 arg1 wall 150:153 plant cell wall 139:153 plant cell wall 139:153 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 6 87 theme in 1030:1031 arg1 methods 1050:1056 in situ degradation methods 1030:1056 in situ degradation methods 1030:1056 Corn silage digestibility was assessed by in situ degradation methods. 36422339 4 88 theme acid 597:600 arg1 content 602:608 bound phenolic acid content 582:608 bound phenolic acid content 582:608 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 11 89 theme phenolic 2081:2088 arg1 acids 2090:2094 ether-linked phenolic acids 2068:2094 ether-linked phenolic acids 2068:2094 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 5 90 theme different 811:819 arg1 FA 821:822 different FA 811:822 different FA 811:822 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 7 91 theme degradation 1365:1375 arg1 characteristics 1377:1391 the degradation characteristics 1361:1391 the degradation characteristics of corn silages 1361:1407 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 11 92 theme fibre 2199:2203 arg1 content 2205:2211 the fibre content 2195:2211 the fibre content 2195:2211 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 10 93 theme ether-linked 1883:1894 arg1 content 1899:1905 the initial ether-linked FA content 1871:1905 the initial ether-linked FA content 1871:1905 The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. 36422339 0 94 theme Ferulic 98:104 arg1 Contents 126:133 Ferulic and p-Coumaric Acid Contents 98:133 Ferulic and p-Coumaric Acid Contents 98:133 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 9 95 theme 72 1587:1588 arg1 h 1590:1590 h 1590:1590 h 1590:1590 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 0 96 theme p-Coumaric 110:119 arg1 Contents 126:133 Ferulic and p-Coumaric Acid Contents 98:133 Ferulic and p-Coumaric Acid Contents 98:133 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 7 97 theme detergent 1149:1157 arg1 related 1181:1187 related 1181:1187 related 1181:1187 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 7 97 theme detergent 1149:1157 arg1 degradability 1086:1098 the effective degradability 1072:1098 the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre 1072:1163 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 9 98 theme rumen 1592:1596 arg1 fermentation 1598:1609 72 h rumen fermentation 1587:1609 72 h rumen fermentation 1587:1609 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 8 99 attach attached 1551:1558 arg1 silages 1572:1578 the corn silages 1563:1578 the corn silages 1563:1578 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 8 99 attach attached 1551:1558 arg2 communities 1539:1549 the bacterial communities 1525:1549 the bacterial communities attached to the corn silages 1525:1578 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 2 100 theme microbes 338:345 arg1 access 322:327 the access 318:327 the access of rumen microbes to cell wall polysaccharides 318:374 These linkages were deemed to hinder the access of rumen microbes to cell wall polysaccharides. 36422339 0 101 theme Degradation 14:24 arg1 Characteristics 26:40 In Situ Rumen Degradation Characteristics 0:40 In Situ Rumen Degradation Characteristics 0:40 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 5 102 theme nylon 858:862 arg1 bags 864:867 nylon bags 858:867 nylon bags 858:867 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 7 103 theme fibre 1133:1137 arg1 detergent 1123:1131 neutral detergent fibre 1115:1137 neutral detergent fibre 1115:1137 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 9 104 theme rumen 1616:1620 arg1 greater 1662:1668 greater 1662:1668 greater 1662:1668 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 9 104 theme rumen 1616:1620 arg1 degradation 1622:1632 the rumen degradation 1612:1632 the rumen degradation of ester-linked FA 1612:1651 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 11 105 from content 2057:2063 arg1 walls 2110:2114 plant cell walls 2099:2114 plant cell walls 2099:2114 In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content. 36422339 4 106 theme nutrient 655:662 arg1 degradability 664:676 the nutrient degradability 651:676 the nutrient degradability 651:676 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 3 107 theme cell 419:422 arg1 wall 424:427 plant cell wall 413:427 plant cell wall 413:427 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 1 108 theme ester 258:262 arg1 bonds 274:278 ester and ether bonds 258:278 bonds 274:278 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 1 109 theme p-coumaric 178:187 arg1 pCA 195:197 pCA 195:197 pCA 195:197 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 1 109 theme p-coumaric 178:187 arg1 acid 189:192 p-coumaric acid 178:192 p-coumaric acid (pCA) 178:198 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 5 110 theme lactating 914:922 arg1 cows 933:936 lactating Holstein cows 914:936 lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h 914:971 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 7 111 theme neutral 1115:1121 arg1 detergent 1123:1131 neutral detergent fibre 1115:1137 neutral detergent fibre 1115:1137 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 7 112 link ether-linked 1196:1207 arg1 FA 1209:1210 the ether-linked FA 1192:1210 the ether-linked FA 1192:1210 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 8 113 theme rumen 1421:1425 arg1 fermentation 1427:1438 24 h rumen fermentation 1416:1438 24 h rumen fermentation 1416:1438 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 2 114 theme cell 350:353 arg1 polysaccharides 360:374 cell wall polysaccharides 350:374 cell wall polysaccharides 350:374 These linkages were deemed to hinder the access of rumen microbes to cell wall polysaccharides. 36422339 1 115 theme ether 268:272 arg1 bonds 274:278 ester and ether bonds 258:278 bonds 274:278 In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. 36422339 7 116 theme phenolic 1323:1330 arg1 acids 1332:1336 phenolic acids 1323:1336 phenolic acids 1323:1336 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 5 117 theme cows 933:936 arg1 rumens 890:895 the rumens 886:895 the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively 886:985 Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. 36422339 7 118 theme matter 1107:1112 arg1 related 1181:1187 related 1181:1187 related 1181:1187 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 7 118 theme matter 1107:1112 arg1 degradability 1086:1098 the effective degradability 1072:1098 the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre 1072:1163 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 9 119 theme FA 1650:1651 arg1 greater 1662:1668 greater 1662:1668 greater 1662:1668 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 9 119 theme FA 1650:1651 arg1 degradation 1622:1632 the rumen degradation 1612:1632 the rumen degradation of ester-linked FA 1612:1651 After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. 36422339 4 120 from silages 640:646 arg1 effect 572:577 the effect 568:577 the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability 568:676 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 4 120 from silages 640:646 arg1 composition 687:697 the composition 683:697 the composition of the attached bacteria 683:722 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 0 121 dep In 0:1 arg1 Situ 3:6 Situ 3:6 Situ 3:6 In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents. 36422339 8 122 theme 24 1416:1417 arg1 h 1419:1419 h 1419:1419 h 1419:1419 After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. 36422339 7 123 theme effective 1076:1084 arg1 related 1181:1187 related 1181:1187 related 1181:1187 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 7 123 theme effective 1076:1084 arg1 degradability 1086:1098 the effective degradability 1072:1098 the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre 1072:1163 As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. 36422339 3 124 theme rumen 395:399 arg1 microbes 401:408 rumen microbes 395:408 rumen microbes 395:408 The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. 36422339 4 125 theme study 546:550 arg1 objective 528:536 The objective 524:536 The objective of this study 524:550 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 4 126 theme attached 706:713 arg1 bacteria 715:722 the attached bacteria 702:722 the attached bacteria 702:722 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 4 127 theme composition 620:630 arg1 effect 572:577 the effect 568:577 the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability 568:676 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 36422339 4 127 theme composition 620:630 arg1 composition 687:697 the composition 683:697 the composition of the attached bacteria 683:722 The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. 35427837 0 0 theme dental 88:93 arg1 pulp 95:98 human dental pulp 82:98 human dental pulp 82:98 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp cells via mTORC1 pathway. 35427837 0 1 from effect 15:20 arg1 differentiation 63:77 odontogenic differentiation 51:77 odontogenic differentiation of human dental pulp 51:98 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp cells via mTORC1 pathway. 35427837 5 2 theme subcutaneous 926:937 arg1 experiment 955:964 a subcutaneous transplantation experiment 924:964 a subcutaneous transplantation experiment 924:964 The odonto-induction effect of O-GlcNAcylation ex vivo was investigated by a subcutaneous transplantation experiment. 35427837 13 3 theme mTORC1 1807:1812 arg1 pathway 1814:1820 the mTORC1 pathway 1803:1820 the mTORC1 pathway 1803:1820 CONCLUSIONS Global O-GlcNAcylation participated in and affected the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway. 35427837 0 4 theme human 82:86 arg1 pulp 95:98 human dental pulp 82:98 human dental pulp 82:98 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp cells via mTORC1 pathway. 35427837 3 5 theme hDPCs 724:728 arg1 odontogenesis 707:719 odontogenesis 707:719 odontogenesis of hDPCs 707:728 Then global O-GlcNAcylation was determined by anti O-linked N-Acetylglucosamine (RL2) Western blot during odontogenesis of hDPCs. 35427837 2 6 theme exclusive 530:538 arg1 transferase 560:570 its exclusive enzyme set O-GlcNAc transferase 526:570 its exclusive enzyme set O-GlcNAc transferase (OGT) 526:576 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 2 6 theme exclusive 530:538 arg1 OGA 595:597 OGA 595:597 OGA 595:597 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 2 6 theme exclusive 530:538 arg1 OGT 573:575 OGT 573:575 OGT 573:575 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 5 7 theme transplantation 939:953 arg1 experiment 955:964 a subcutaneous transplantation experiment 924:964 a subcutaneous transplantation experiment 924:964 The odonto-induction effect of O-GlcNAcylation ex vivo was investigated by a subcutaneous transplantation experiment. 35427837 5 8 dep ex 896:897 arg1 vivo 899:902 vivo 899:902 vivo 899:902 The odonto-induction effect of O-GlcNAcylation ex vivo was investigated by a subcutaneous transplantation experiment. 35427837 4 9 theme OGA 775:777 arg1 knockdown 754:762 knockdown 754:762 knockdown 754:762 Further, inhibition or knockdown of OGT and OGA were achieved by specific inhibitors or siRNA in vitro, respectively. 35427837 4 9 theme OGA 775:777 arg1 inhibition 740:749 inhibition 740:749 inhibition 740:749 Further, inhibition or knockdown of OGT and OGA were achieved by specific inhibitors or siRNA in vitro, respectively. 35427837 0 10 theme pulp 95:98 arg1 differentiation 63:77 odontogenic differentiation 51:77 odontogenic differentiation of human dental pulp 51:98 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp cells via mTORC1 pathway. 35427837 6 11 theme O-GlcNAc 981:988 arg1 modification 990:1001 the O-GlcNAc modification 977:1001 the O-GlcNAc modification of RAPTOR 977:1011 Moreover, the O-GlcNAc modification of RAPTOR was confirmed by immunoprecipitation. 35427837 1 12 theme odontogenic 307:317 arg1 differentiation 319:333 differentiation 319:333 differentiation 319:333 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 0 13 theme mTORC1 110:115 arg1 pathway 117:123 mTORC1 pathway 110:123 mTORC1 pathway 110:123 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp cells via mTORC1 pathway. 35427837 1 14 from mineralization 339:352 arg1 hDPCs 382:386 hDPCs 382:386 hDPCs 382:386 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 14 from mineralization 339:352 arg1 cells 375:379 human dental pulp cells 357:379 human dental pulp cells (hDPCs) 357:387 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 15 theme global 167:172 arg1 N-Acetylglucosamine 183:201 global O-linked N-Acetylglucosamine 167:201 global O-linked N-Acetylglucosamine modification (O-GlcNAcylation) 167:232 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 15 theme global 167:172 arg1 O-GlcNAcylation 217:231 O-GlcNAcylation 217:231 O-GlcNAcylation 217:231 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 15 theme global 167:172 arg1 modification 283:294 a prevalent nutrient-sensitive post-translation modification 235:294 a prevalent nutrient-sensitive post-translation modification 235:294 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 2 16 theme O-GlcNAc 551:558 arg1 transferase 560:570 its exclusive enzyme set O-GlcNAc transferase 526:570 its exclusive enzyme set O-GlcNAc transferase (OGT) 526:576 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 2 16 theme O-GlcNAc 551:558 arg1 OGA 595:597 OGA 595:597 OGA 595:597 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 2 16 theme O-GlcNAc 551:558 arg1 OGT 573:575 OGT 573:575 OGT 573:575 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 2 17 dep performed 465:473 arg1 First 397:401 First 397:401 First 397:401 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 9 18 theme hDPCs 1304:1308 arg1 odontogenesis 1287:1299 odontogenesis 1287:1299 odontogenesis of hDPCs 1287:1308 During odontogenesis of hDPCs, global O-GlcNAcylation was significantly increased. 35427837 4 19 theme specific 796:803 arg1 inhibitors 805:814 specific inhibitors 796:814 specific inhibitors 796:814 Further, inhibition or knockdown of OGT and OGA were achieved by specific inhibitors or siRNA in vitro, respectively. 35427837 10 20 theme O-GlcNAcylation 1390:1404 arg1 increase 1366:1373 An increase 1363:1373 An increase 1363:1373 An increase or decrease of O-GlcNAcylation significantly boosted or blunted odontogenic differentiation, respectively. 35427837 10 20 theme O-GlcNAcylation 1390:1404 arg1 decrease 1378:1385 decrease 1378:1385 decrease of O-GlcNAcylation 1378:1404 An increase or decrease of O-GlcNAcylation significantly boosted or blunted odontogenic differentiation, respectively. 35427837 1 21 theme O-linked 174:181 arg1 N-Acetylglucosamine 183:201 global O-linked N-Acetylglucosamine 167:201 global O-linked N-Acetylglucosamine modification (O-GlcNAcylation) 167:232 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 21 theme O-linked 174:181 arg1 O-GlcNAcylation 217:231 O-GlcNAcylation 217:231 O-GlcNAcylation 217:231 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 21 theme O-linked 174:181 arg1 modification 283:294 a prevalent nutrient-sensitive post-translation modification 235:294 a prevalent nutrient-sensitive post-translation modification 235:294 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 0 22 theme beneficial 4:13 arg1 effect 15:20 The beneficial effect 0:20 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp 0:98 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp cells via mTORC1 pathway. 35427837 1 23 from differentiation 319:333 arg1 hDPCs 382:386 hDPCs 382:386 hDPCs 382:386 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 23 from differentiation 319:333 arg1 cells 375:379 human dental pulp cells 357:379 human dental pulp cells (hDPCs) 357:387 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 11 24 theme downstream 1543:1552 arg1 targets 1554:1560 the downstream targets 1539:1560 the downstream targets of mTORC1 1539:1570 The fluctuation of O-GlcNAcylation continuously impacted the downstream targets of mTORC1. 35427837 14 25 theme targeting 1829:1837 arg1 O-GlcNAcylation 1839:1853 targeting O-GlcNAcylation 1829:1853 targeting O-GlcNAcylation 1829:1853 Thus, targeting O-GlcNAcylation might be a potential therapeutic intervention for pulp repair and regeneration. 35427837 14 25 theme targeting 1829:1837 arg1 intervention 1888:1899 a potential therapeutic intervention 1864:1899 a potential therapeutic intervention for pulp repair and regeneration 1864:1932 Thus, targeting O-GlcNAcylation might be a potential therapeutic intervention for pulp repair and regeneration. 35427837 1 26 link O-linked 174:181 arg1 N-Acetylglucosamine 183:201 global O-linked N-Acetylglucosamine 167:201 global O-linked N-Acetylglucosamine modification (O-GlcNAcylation) 167:232 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 26 link O-linked 174:181 arg1 O-GlcNAcylation 217:231 O-GlcNAcylation 217:231 O-GlcNAcylation 217:231 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 26 link O-linked 174:181 arg1 modification 283:294 a prevalent nutrient-sensitive post-translation modification 235:294 a prevalent nutrient-sensitive post-translation modification 235:294 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 5 27 theme ex 896:897 arg1 effect 870:875 The odonto-induction effect 849:875 The odonto-induction effect of O-GlcNAcylation ex vivo 849:902 The odonto-induction effect of O-GlcNAcylation ex vivo was investigated by a subcutaneous transplantation experiment. 35427837 4 28 theme OGT 767:769 arg1 knockdown 754:762 knockdown 754:762 knockdown 754:762 Further, inhibition or knockdown of OGT and OGA were achieved by specific inhibitors or siRNA in vitro, respectively. 35427837 4 28 theme OGT 767:769 arg1 inhibition 740:749 inhibition 740:749 inhibition 740:749 Further, inhibition or knockdown of OGT and OGA were achieved by specific inhibitors or siRNA in vitro, respectively. 35427837 12 29 mod modified 1598:1605 arg1 RAPTOR 1587:1592 RAPTOR 1587:1592 RAPTOR 1587:1592 Consistently, RAPTOR was modified by O-GlcNAcylation, which was necessary for inducing odontogenesis. 35427837 12 29 mod modified 1598:1605 arg3 O-GlcNAcylation 1610:1624 O-GlcNAcylation 1610:1624 O-GlcNAcylation 1610:1624 Consistently, RAPTOR was modified by O-GlcNAcylation, which was necessary for inducing odontogenesis. 35427837 3 30 link O-linked 652:659 arg1 RL2 682:684 RL2 682:684 RL2 682:684 Then global O-GlcNAcylation was determined by anti O-linked N-Acetylglucosamine (RL2) Western blot during odontogenesis of hDPCs. 35427837 3 30 link O-linked 652:659 arg1 N-Acetylglucosamine 661:679 O-linked N-Acetylglucosamine 652:679 anti O-linked N-Acetylglucosamine (RL2) Western blot 647:698 Then global O-GlcNAcylation was determined by anti O-linked N-Acetylglucosamine (RL2) Western blot during odontogenesis of hDPCs. 35427837 8 31 theme pulp 1262:1265 arg1 fibroblasts 1267:1277 pulp fibroblasts 1262:1277 pulp fibroblasts 1262:1277 RESULTS The signals of O-GlcNAc became more enriched in the odontoblasts compared to pulp fibroblasts. 35427837 7 32 theme global 1153:1158 arg1 O-GlcNAcylation 1160:1174 enhanced global O-GlcNAcylation 1144:1174 enhanced global O-GlcNAcylation 1144:1174 Odontogenic differentiation assays also investigated the indispensable role of RAPTOR during enhanced global O-GlcNAcylation. 35427837 1 33 dep investigate 139:149 arg1 whether 151:157 whether 151:157 whether 151:157 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 10 34 theme odontogenic 1439:1449 arg1 differentiation 1451:1465 odontogenic differentiation 1439:1465 odontogenic differentiation 1439:1465 An increase or decrease of O-GlcNAcylation significantly boosted or blunted odontogenic differentiation, respectively. 35427837 5 35 theme odonto-induction 853:868 arg1 effect 870:875 The odonto-induction effect 849:875 The odonto-induction effect of O-GlcNAcylation ex vivo 849:902 The odonto-induction effect of O-GlcNAcylation ex vivo was investigated by a subcutaneous transplantation experiment. 35427837 9 36 theme global 1311:1316 arg1 O-GlcNAcylation 1318:1332 global O-GlcNAcylation 1311:1332 global O-GlcNAcylation 1311:1332 During odontogenesis of hDPCs, global O-GlcNAcylation was significantly increased. 35427837 1 37 dep whether 151:157 arg1 regulates 297:305 regulates 297:305 regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs) 297:387 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 2 38 theme tissue 453:458 arg1 sections 429:436 sections 429:436 sections of dental pulp tissue 429:458 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 0 39 theme O-GlcNAcylation 32:46 arg1 effect 15:20 The beneficial effect 0:20 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp 0:98 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp cells via mTORC1 pathway. 35427837 6 40 theme RAPTOR 1006:1011 arg1 modification 990:1001 the O-GlcNAc modification 977:1001 the O-GlcNAc modification of RAPTOR 977:1011 Moreover, the O-GlcNAc modification of RAPTOR was confirmed by immunoprecipitation. 35427837 3 41 theme Western 687:693 arg1 blot 695:698 anti O-linked N-Acetylglucosamine (RL2) Western blot 647:698 anti O-linked N-Acetylglucosamine (RL2) Western blot 647:698 Then global O-GlcNAcylation was determined by anti O-linked N-Acetylglucosamine (RL2) Western blot during odontogenesis of hDPCs. 35427837 1 42 dep N-Acetylglucosamine 183:201 arg1 modification 203:214 modification 203:214 global O-linked N-Acetylglucosamine modification (O-GlcNAcylation) 167:232 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 13 43 theme Global 1687:1692 arg1 O-GlcNAcylation 1694:1708 Global O-GlcNAcylation 1687:1708 Global O-GlcNAcylation 1687:1708 CONCLUSIONS Global O-GlcNAcylation participated in and affected the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway. 35427837 2 44 theme pulp 448:451 arg1 tissue 453:458 dental pulp tissue 441:458 dental pulp tissue 441:458 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 0 45 theme global 25:30 arg1 O-GlcNAcylation 32:46 global O-GlcNAcylation 25:46 global O-GlcNAcylation 25:46 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp cells via mTORC1 pathway. 35427837 1 46 theme human 357:361 arg1 hDPCs 382:386 hDPCs 382:386 hDPCs 382:386 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 46 theme human 357:361 arg1 cells 375:379 human dental pulp cells 357:379 human dental pulp cells (hDPCs) 357:387 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 2 47 theme O-GlcNAcylation 506:520 arg1 distributions 489:501 the distributions 485:501 the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) 485:598 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 11 48 theme mTORC1 1565:1570 arg1 targets 1554:1560 the downstream targets 1539:1560 the downstream targets of mTORC1 1539:1570 The fluctuation of O-GlcNAcylation continuously impacted the downstream targets of mTORC1. 35427837 2 49 theme dental 441:446 arg1 tissue 453:458 dental pulp tissue 441:458 dental pulp tissue 441:458 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 0 50 theme odontogenic 51:61 arg1 differentiation 63:77 odontogenic differentiation 51:77 odontogenic differentiation of human dental pulp 51:98 The beneficial effect of global O-GlcNAcylation on odontogenic differentiation of human dental pulp cells via mTORC1 pathway. 35427837 1 51 theme dental 363:368 arg1 hDPCs 382:386 hDPCs 382:386 hDPCs 382:386 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 51 theme dental 363:368 arg1 cells 375:379 human dental pulp cells 357:379 human dental pulp cells (hDPCs) 357:387 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 8 52 theme O-GlcNAc 1200:1207 arg1 signals 1189:1195 The signals 1185:1195 The signals of O-GlcNAc 1185:1207 RESULTS The signals of O-GlcNAc became more enriched in the odontoblasts compared to pulp fibroblasts. 35427837 14 53 dep potential 1866:1874 arg1 therapeutic 1876:1886 therapeutic 1876:1886 therapeutic 1876:1886 Thus, targeting O-GlcNAcylation might be a potential therapeutic intervention for pulp repair and regeneration. 35427837 3 54 theme global 606:611 arg1 O-GlcNAcylation 613:627 Then global O-GlcNAcylation 601:627 Then global O-GlcNAcylation 601:627 Then global O-GlcNAcylation was determined by anti O-linked N-Acetylglucosamine (RL2) Western blot during odontogenesis of hDPCs. 35427837 2 55 from assays 419:424 arg1 sections 429:436 sections 429:436 sections of dental pulp tissue 429:458 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 13 56 theme odontogenic 1743:1753 arg1 differentiation 1755:1769 the odontogenic differentiation 1739:1769 the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway 1739:1820 CONCLUSIONS Global O-GlcNAcylation participated in and affected the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway. 35427837 7 57 theme enhanced 1144:1151 arg1 O-GlcNAcylation 1160:1174 enhanced global O-GlcNAcylation 1144:1174 enhanced global O-GlcNAcylation 1144:1174 Odontogenic differentiation assays also investigated the indispensable role of RAPTOR during enhanced global O-GlcNAcylation. 35427837 1 58 theme pulp 370:373 arg1 hDPCs 382:386 hDPCs 382:386 hDPCs 382:386 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 58 theme pulp 370:373 arg1 cells 375:379 human dental pulp cells 357:379 human dental pulp cells (hDPCs) 357:387 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 7 59 theme RAPTOR 1130:1135 arg1 role 1122:1125 the indispensable role 1104:1125 the indispensable role of RAPTOR during enhanced global O-GlcNAcylation 1104:1174 Odontogenic differentiation assays also investigated the indispensable role of RAPTOR during enhanced global O-GlcNAcylation. 35427837 2 60 theme transferase 560:570 arg1 distributions 489:501 the distributions 485:501 the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) 485:598 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 7 61 theme indispensable 1108:1120 arg1 role 1122:1125 the indispensable role 1104:1125 the indispensable role of RAPTOR during enhanced global O-GlcNAcylation 1104:1174 Odontogenic differentiation assays also investigated the indispensable role of RAPTOR during enhanced global O-GlcNAcylation. 35427837 14 62 theme potential 1866:1874 arg1 O-GlcNAcylation 1839:1853 targeting O-GlcNAcylation 1829:1853 targeting O-GlcNAcylation 1829:1853 Thus, targeting O-GlcNAcylation might be a potential therapeutic intervention for pulp repair and regeneration. 35427837 14 62 theme potential 1866:1874 arg1 intervention 1888:1899 a potential therapeutic intervention 1864:1899 a potential therapeutic intervention for pulp repair and regeneration 1864:1932 Thus, targeting O-GlcNAcylation might be a potential therapeutic intervention for pulp repair and regeneration. 35427837 3 63 theme O-linked 652:659 arg1 RL2 682:684 RL2 682:684 RL2 682:684 Then global O-GlcNAcylation was determined by anti O-linked N-Acetylglucosamine (RL2) Western blot during odontogenesis of hDPCs. 35427837 3 63 theme O-linked 652:659 arg1 N-Acetylglucosamine 661:679 O-linked N-Acetylglucosamine 652:679 anti O-linked N-Acetylglucosamine (RL2) Western blot 647:698 Then global O-GlcNAcylation was determined by anti O-linked N-Acetylglucosamine (RL2) Western blot during odontogenesis of hDPCs. 35427837 11 64 theme O-GlcNAcylation 1501:1515 arg1 fluctuation 1486:1496 The fluctuation 1482:1496 The fluctuation of O-GlcNAcylation 1482:1515 The fluctuation of O-GlcNAcylation continuously impacted the downstream targets of mTORC1. 35427837 14 65 theme pulp 1905:1908 arg1 repair 1910:1915 pulp repair 1905:1915 pulp repair 1905:1915 Thus, targeting O-GlcNAcylation might be a potential therapeutic intervention for pulp repair and regeneration. 35427837 3 66 theme N-Acetylglucosamine 661:679 arg1 blot 695:698 anti O-linked N-Acetylglucosamine (RL2) Western blot 647:698 anti O-linked N-Acetylglucosamine (RL2) Western blot 647:698 Then global O-GlcNAcylation was determined by anti O-linked N-Acetylglucosamine (RL2) Western blot during odontogenesis of hDPCs. 35427837 7 67 theme Odontogenic 1051:1061 arg1 assays 1079:1084 Odontogenic differentiation assays 1051:1084 Odontogenic differentiation assays 1051:1084 Odontogenic differentiation assays also investigated the indispensable role of RAPTOR during enhanced global O-GlcNAcylation. 35427837 1 68 theme prevalent 237:245 arg1 N-Acetylglucosamine 183:201 global O-linked N-Acetylglucosamine 167:201 global O-linked N-Acetylglucosamine modification (O-GlcNAcylation) 167:232 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 68 theme prevalent 237:245 arg1 modification 283:294 a prevalent nutrient-sensitive post-translation modification 235:294 a prevalent nutrient-sensitive post-translation modification 235:294 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 2 69 theme set 547:549 arg1 transferase 560:570 its exclusive enzyme set O-GlcNAc transferase 526:570 its exclusive enzyme set O-GlcNAc transferase (OGT) 526:576 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 2 69 theme set 547:549 arg1 OGA 595:597 OGA 595:597 OGA 595:597 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 2 69 theme set 547:549 arg1 OGT 573:575 OGT 573:575 OGT 573:575 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 5 70 theme O-GlcNAcylation 880:894 arg1 effect 870:875 The odonto-induction effect 849:875 The odonto-induction effect of O-GlcNAcylation ex vivo 849:902 The odonto-induction effect of O-GlcNAcylation ex vivo was investigated by a subcutaneous transplantation experiment. 35427837 7 71 theme differentiation 1063:1077 arg1 assays 1079:1084 Odontogenic differentiation assays 1051:1084 Odontogenic differentiation assays 1051:1084 Odontogenic differentiation assays also investigated the indispensable role of RAPTOR during enhanced global O-GlcNAcylation. 35427837 2 72 theme immunostaining 404:417 arg1 assays 419:424 immunostaining assays 404:424 immunostaining assays on sections of dental pulp tissue 404:458 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 1 73 theme nutrient-sensitive 247:264 arg1 N-Acetylglucosamine 183:201 global O-linked N-Acetylglucosamine 167:201 global O-linked N-Acetylglucosamine modification (O-GlcNAcylation) 167:232 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 73 theme nutrient-sensitive 247:264 arg1 modification 283:294 a prevalent nutrient-sensitive post-translation modification 235:294 a prevalent nutrient-sensitive post-translation modification 235:294 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 2 74 theme enzyme 540:545 arg1 transferase 560:570 its exclusive enzyme set O-GlcNAc transferase 526:570 its exclusive enzyme set O-GlcNAc transferase (OGT) 526:576 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 2 74 theme enzyme 540:545 arg1 OGA 595:597 OGA 595:597 OGA 595:597 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 2 74 theme enzyme 540:545 arg1 OGT 573:575 OGT 573:575 OGT 573:575 DESIGN First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 35427837 13 75 dep CONCLUSIONS 1675:1685 arg1 participated 1710:1721 participated 1710:1721 participated in 1710:1724 CONCLUSIONS Global O-GlcNAcylation participated in and affected the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway. 35427837 13 75 dep CONCLUSIONS 1675:1685 arg1 affected 1730:1737 affected 1730:1737 affected the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway 1730:1820 CONCLUSIONS Global O-GlcNAcylation participated in and affected the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway. 35427837 3 76 theme anti 647:650 arg1 blot 695:698 anti O-linked N-Acetylglucosamine (RL2) Western blot 647:698 anti O-linked N-Acetylglucosamine (RL2) Western blot 647:698 Then global O-GlcNAcylation was determined by anti O-linked N-Acetylglucosamine (RL2) Western blot during odontogenesis of hDPCs. 35427837 13 77 theme hDPCs 1774:1778 arg1 differentiation 1755:1769 the odontogenic differentiation 1739:1769 the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway 1739:1820 CONCLUSIONS Global O-GlcNAcylation participated in and affected the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway. 35427837 8 78 dep RESULTS 1177:1183 arg1 became 1209:1214 became 1209:1214 became more enriched in the odontoblasts compared to pulp fibroblasts 1209:1277 RESULTS The signals of O-GlcNAc became more enriched in the odontoblasts compared to pulp fibroblasts. 35427837 1 79 theme post-translation 266:281 arg1 N-Acetylglucosamine 183:201 global O-linked N-Acetylglucosamine 167:201 global O-linked N-Acetylglucosamine modification (O-GlcNAcylation) 167:232 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35427837 1 79 theme post-translation 266:281 arg1 modification 283:294 a prevalent nutrient-sensitive post-translation modification 235:294 a prevalent nutrient-sensitive post-translation modification 235:294 OBJECTIVE To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs). 35151483 6 0 theme desialylated 968:979 arg1 isolates 986:993 native and desialylated κ-CN isolates 957:993 native and desialylated κ-CN isolates 957:993 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 8 1 from rates 1418:1422 arg1 phases 1455:1460 both gastric and intestinal phases 1427:1460 both gastric and intestinal phases 1427:1460 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 6 2 from degradations 941:952 arg1 phases 1021:1026 gastric and intestinal phases 998:1026 gastric and intestinal phases 998:1026 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 9 3 theme intestinal 1726:1735 arg1 phase 1737:1741 the intestinal phase 1722:1741 the intestinal phase 1722:1741 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 6 4 theme mass 1155:1158 arg1 spectrometry 1160:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 3 5 theme substrate 485:493 arg1 molecules 495:503 substrate molecules 485:503 substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model 485:575 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 5 theme substrate 485:493 arg1 κ-CN 381:384 κ-CN 381:384 κ-CN 381:384 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 5 6 theme anion 825:829 arg1 chromatography 840:853 anion exchange chromatography 825:853 anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively 825:930 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 4 7 theme desialylation 749:761 arg1 assays 773:778 desialylation enzymatic assays 749:778 desialylation enzymatic assays 749:778 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 6 8 theme dodecyl 1056:1062 arg1 sulfate-PAGE 1064:1075 sodium dodecyl sulfate-PAGE 1049:1075 sodium dodecyl sulfate-PAGE 1049:1075 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 3 9 used used 477:480 arg2 κ-CN 381:384 κ-CN 381:384 κ-CN 381:384 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 9 used used 477:480 arg2 molecules 495:503 substrate molecules 485:503 substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model 485:575 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 6 10 theme electrospray 1131:1142 arg1 spectrometry 1160:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 2 11 theme study 238:242 arg1 aim 219:221 the aim 215:221 the aim of the present study 215:242 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35151483 1 12 with Milk 92:95 arg1 phenotypes 126:135 different κ-casein (CN) phenotypes 102:135 different κ-casein (CN) phenotypes 102:135 Milk with different κ-casein (CN) phenotypes has previously been found to influence its gastric digestion rate. 35151483 4 13 theme removal 605:611 arg1 effect 595:600 the effect 591:600 the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants 591:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 9 14 theme oligosaccharides 1981:1996 arg1 desialylation 1951:1963 desialylation 1951:1963 desialylation of the O-linked oligosaccharides 1951:1996 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 6 15 theme liquid 1109:1114 arg1 spectrometry 1160:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 2 16 theme genetic 279:285 arg1 variation 287:295 genetic variation 279:295 genetic variation 279:295 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35151483 9 17 theme B 1769:1769 arg1 desialylation 1744:1756 desialylation 1744:1756 desialylation of variant B 1744:1769 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 1 18 theme gastric 180:186 arg1 rate 198:201 its gastric digestion rate 176:201 its gastric digestion rate 176:201 Milk with different κ-casein (CN) phenotypes has previously been found to influence its gastric digestion rate. 35151483 1 19 theme κ-casein 112:119 arg1 phenotypes 126:135 different κ-casein (CN) phenotypes 102:135 different κ-casein (CN) phenotypes 102:135 Milk with different κ-casein (CN) phenotypes has previously been found to influence its gastric digestion rate. 35151483 9 20 theme better 1780:1785 arg1 digestion 1787:1795 better digestion 1780:1795 better digestion 1780:1795 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 9 21 gly desialylation 1744:1756 arg1 B 1769:1769 variant B 1761:1769 variant B 1761:1769 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 4 22 theme present 642:648 arg1 acids 636:640 the terminal sialic acids 616:640 the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants 616:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 5 23 theme % 916:916 arg1 variants 872:879 variants A, B, and E 872:891 variants A, B, and E of 93.0, 97.1, and 90.0%, respectively 872:930 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 5 23 theme % 916:916 arg1 B 884:884 B 884:884 B 884:884 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 5 23 theme % 916:916 arg1 E 891:891 E 891:891 E 891:891 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 5 23 theme % 916:916 arg1 A 881:881 A 881:881 A 881:881 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 5 24 theme exchange 831:838 arg1 chromatography 840:853 anion exchange chromatography 825:853 anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively 825:930 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 2 25 theme present 230:236 arg1 study 238:242 the present study 226:242 the present study 226:242 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35151483 3 26 theme digestion 561:569 arg1 model 571:575 the INFOGEST 2.0 in vitro static digestion model 528:575 the INFOGEST 2.0 in vitro static digestion model 528:575 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 1 27 theme CN 122:123 arg1 phenotypes 126:135 different κ-casein (CN) phenotypes 102:135 different κ-casein (CN) phenotypes 102:135 Milk with different κ-casein (CN) phenotypes has previously been found to influence its gastric digestion rate. 35151483 9 28 theme gastric 1599:1605 arg1 phase 1607:1611 the gastric phase 1595:1611 the gastric phase 1595:1611 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 5 29 dep variants 872:879 arg1 variants 872:879 variants A, B, and E 872:891 variants A, B, and E of 93.0, 97.1, and 90.0%, respectively 872:930 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 5 29 dep variants 872:879 arg1 B 884:884 B 884:884 B 884:884 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 5 29 dep variants 872:879 arg1 E 891:891 E 891:891 E 891:891 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 5 29 dep variants 872:879 arg1 A 881:881 A 881:881 A 881:881 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 4 30 theme sialic 629:634 arg1 acids 636:640 the terminal sialic acids 616:640 the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants 616:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 0 31 from Effects 0:6 arg1 digestibility 56:68 in vitro digestibility 47:68 in vitro digestibility of purified κ-casein 47:89 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein. 35151483 4 32 theme κ-CN 699:702 arg1 A 704:704 κ-CN A 699:704 κ-CN A 699:704 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 0 33 theme κ-casein 82:89 arg1 digestibility 56:68 in vitro digestibility 47:68 in vitro digestibility of purified κ-casein 47:89 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein. 35151483 6 34 theme hydrolysis 1088:1097 arg1 spectrometry 1160:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 6 34 theme hydrolysis 1088:1097 arg1 degree 1078:1083 degree 1078:1083 degree of hydrolysis (DH) 1078:1102 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 6 34 theme hydrolysis 1088:1097 arg1 sulfate-PAGE 1064:1075 sodium dodecyl sulfate-PAGE 1049:1075 sodium dodecyl sulfate-PAGE 1049:1075 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 3 35 dep phenotypes 448:457 arg1 AA 459:460 AA 459:460 AA 459:460 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 35 dep phenotypes 448:457 arg1 phenotypes 448:457 κ-CN phenotypes AA, BB, or EE 443:471 κ-CN phenotypes AA, BB, or EE 443:471 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 35 dep phenotypes 448:457 arg1 BB 463:464 BB 463:464 BB 463:464 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 35 dep phenotypes 448:457 arg1 EE 470:471 EE 470:471 EE 470:471 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 5 36 with chromatography 840:853 arg1 purities 860:867 purities 860:867 purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively 860:930 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 2 37 theme κ-CN 362:365 arg1 process 351:357 the in vitro digestion process 328:357 the in vitro digestion process of κ-CN 328:365 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35151483 7 38 theme κ-CN 1216:1219 arg1 molecules 1221:1229 the κ-CN molecules 1212:1229 the κ-CN molecules 1212:1229 It was shown that after purification, the κ-CN molecules reassembled into multimer states, which then constituted the basis for the digestion studies. 35151483 9 39 theme B 1658:1658 arg1 digestion 1637:1645 digestion 1637:1645 digestion of variant B 1637:1658 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 8 40 theme faster 1392:1397 arg1 rates 1418:1422 faster in vitro digestion rates 1392:1422 faster in vitro digestion rates in both gastric and intestinal phases 1392:1460 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 9 41 theme low 1858:1860 arg1 degree 1876:1881 low glycosylation degree 1858:1881 low glycosylation degree of purified κ-CN 1858:1898 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 6 42 theme Protein 933:939 arg1 degradations 941:952 Protein degradations 933:952 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases 933:1026 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 10 43 theme dairy 2067:2071 arg1 products 2073:2080 dairy products 2067:2080 dairy products 2067:2080 This finding could be applied to produce dairy products with enhanced digestibility. 35151483 0 44 theme genetic 11:17 arg1 variants 19:26 genetic variants 11:26 genetic variants 11:26 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein. 35151483 9 45 theme comparable 1670:1679 arg1 rate 1665:1668 a rate 1663:1668 a rate comparable with native variants A and E 1663:1708 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 9 46 theme purified 1886:1893 arg1 κ-CN 1895:1898 purified κ-CN 1886:1898 purified κ-CN 1886:1898 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 4 47 theme variants 724:731 arg1 oligosaccharides 666:681 the O-linked oligosaccharides 653:681 the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants 653:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 9 48 theme native 1686:1691 arg1 E 1708:1708 E 1708:1708 E 1708:1708 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 9 48 theme native 1686:1691 arg1 A 1702:1702 A 1702:1702 A 1702:1702 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 9 48 theme native 1686:1691 arg1 variants 1693:1700 native variants A and E 1686:1708 native variants A and E 1686:1708 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 2 49 theme sialylation 313:323 arg1 contributions 262:274 contributions 262:274 contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN 262:365 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35151483 9 50 dep variants 1693:1700 arg1 E 1708:1708 E 1708:1708 E 1708:1708 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 9 50 dep variants 1693:1700 arg1 A 1702:1702 A 1702:1702 A 1702:1702 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 9 50 dep variants 1693:1700 arg1 variants 1693:1700 native variants A and E 1686:1708 native variants A and E 1686:1708 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 3 51 theme κ-CN 443:446 arg1 AA 459:460 AA 459:460 AA 459:460 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 51 theme κ-CN 443:446 arg1 phenotypes 448:457 κ-CN phenotypes AA, BB, or EE 443:471 κ-CN phenotypes AA, BB, or EE 443:471 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 51 theme κ-CN 443:446 arg1 BB 463:464 BB 463:464 BB 463:464 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 51 theme κ-CN 443:446 arg1 EE 470:471 EE 470:471 EE 470:471 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 8 52 theme gastric 1516:1522 arg1 rates 1549:1553 both gastric and intestinal digestion rates 1511:1553 both gastric and intestinal digestion rates for all variants 1511:1570 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 8 53 dep in 1399:1400 arg1 vitro 1402:1406 vitro 1402:1406 vitro 1402:1406 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 6 54 theme sodium 1049:1054 arg1 sulfate-PAGE 1064:1075 sodium dodecyl sulfate-PAGE 1049:1075 sodium dodecyl sulfate-PAGE 1049:1075 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 0 55 gly sialylation 32:42 arg1 κ-casein 82:89 purified κ-casein 73:89 purified κ-casein 73:89 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein. 35151483 9 56 theme digestion 1925:1933 arg1 rates 1935:1939 digestion rates 1925:1939 vitro digestion rates 1919:1939 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 4 57 theme E 714:714 arg1 variants 724:731 the purified κ-CN A, B, and E protein variants 686:731 the purified κ-CN A, B, and E protein variants 686:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 8 58 theme intestinal 1528:1537 arg1 rates 1549:1553 both gastric and intestinal digestion rates 1511:1553 both gastric and intestinal digestion rates for all variants 1511:1570 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 6 59 theme κ-CN 981:984 arg1 isolates 986:993 native and desialylated κ-CN isolates 957:993 native and desialylated κ-CN isolates 957:993 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 4 60 attach present 642:648 arg2 acids 636:640 the terminal sialic acids 616:640 the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants 616:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 4 60 attach present 642:648 arg1 oligosaccharides 666:681 the O-linked oligosaccharides 653:681 the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants 653:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 4 61 link O-linked 657:664 arg1 oligosaccharides 666:681 the O-linked oligosaccharides 653:681 the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants 653:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 8 62 theme B. 1484:1485 arg1 Desialylation 1487:1499 variant B. Desialylation 1476:1499 variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH 1476:1589 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 3 63 theme model 508:512 arg1 studies 514:520 model studies 508:520 model studies using the INFOGEST 2.0 in vitro static digestion model 508:575 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 6 64 theme ionization 1144:1153 arg1 spectrometry 1160:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 9 65 with comparable 1670:1679 arg1 E 1708:1708 E 1708:1708 E 1708:1708 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 9 65 with comparable 1670:1679 arg1 A 1702:1702 A 1702:1702 A 1702:1702 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 9 65 with comparable 1670:1679 arg1 variants 1693:1700 native variants A and E 1686:1708 native variants A and E 1686:1708 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 9 66 link O-linked 1972:1979 arg1 oligosaccharides 1981:1996 the O-linked oligosaccharides 1968:1996 the O-linked oligosaccharides 1968:1996 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 7 67 theme digestion 1306:1314 arg1 studies 1316:1322 the digestion studies 1302:1322 the digestion studies 1302:1322 It was shown that after purification, the κ-CN molecules reassembled into multimer states, which then constituted the basis for the digestion studies. 35151483 9 68 theme O-linked 1972:1979 arg1 oligosaccharides 1981:1996 the O-linked oligosaccharides 1968:1996 the O-linked oligosaccharides 1968:1996 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 6 69 theme chromatography 1116:1129 arg1 spectrometry 1160:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 liquid chromatography electrospray ionization mass spectrometry 1109:1171 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 2 70 theme variation 287:295 arg1 contributions 262:274 contributions 262:274 contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN 262:365 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35151483 4 71 theme enzymatic 763:771 arg1 assays 773:778 desialylation enzymatic assays 749:778 desialylation enzymatic assays 749:778 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 9 72 theme variant 1761:1767 arg1 B 1769:1769 variant B 1761:1769 variant B 1761:1769 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 3 73 dep in 545:546 arg1 vitro 548:552 vitro 548:552 vitro 548:552 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 9 74 dep rates 1935:1939 arg1 vitro 1919:1923 vitro digestion rates 1919:1939 vitro digestion rates 1919:1939 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 3 75 with cows 433:436 arg1 AA 459:460 AA 459:460 AA 459:460 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 75 with cows 433:436 arg1 phenotypes 448:457 κ-CN phenotypes AA, BB, or EE 443:471 κ-CN phenotypes AA, BB, or EE 443:471 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 75 with cows 433:436 arg1 BB 463:464 BB 463:464 BB 463:464 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 75 with cows 433:436 arg1 EE 470:471 EE 470:471 EE 470:471 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 3 76 theme INFOGEST 532:539 arg1 model 571:575 the INFOGEST 2.0 in vitro static digestion model 528:575 the INFOGEST 2.0 in vitro static digestion model 528:575 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 1 77 theme digestion 188:196 arg1 rate 198:201 its gastric digestion rate 176:201 its gastric digestion rate 176:201 Milk with different κ-casein (CN) phenotypes has previously been found to influence its gastric digestion rate. 35151483 1 78 theme different 102:110 arg1 phenotypes 126:135 different κ-casein (CN) phenotypes 102:135 different κ-casein (CN) phenotypes 102:135 Milk with different κ-casein (CN) phenotypes has previously been found to influence its gastric digestion rate. 35151483 8 79 theme purified 1344:1351 arg1 variants 1353:1360 purified variants A and E 1344:1368 purified variants A and E 1344:1368 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 8 79 theme purified 1344:1351 arg1 E 1368:1368 E 1368:1368 E 1368:1368 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 8 79 theme purified 1344:1351 arg1 A 1362:1362 A 1362:1362 A 1362:1362 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 9 80 theme native 1802:1807 arg1 A 1809:1809 native A 1802:1809 native A 1802:1809 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 4 81 theme acids 636:640 arg1 removal 605:611 removal 605:611 removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants 605:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 3 82 from molecules 495:503 arg1 studies 514:520 model studies 508:520 model studies using the INFOGEST 2.0 in vitro static digestion model 508:575 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 9 83 dep promoted 1628:1635 arg1 whereas 1711:1717 whereas 1711:1717 whereas 1711:1717 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 3 84 theme static 554:559 arg1 model 571:575 the INFOGEST 2.0 in vitro static digestion model 528:575 the INFOGEST 2.0 in vitro static digestion model 528:575 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 7 85 theme multimer 1248:1255 arg1 states 1257:1262 multimer states 1248:1262 multimer states 1248:1262 It was shown that after purification, the κ-CN molecules reassembled into multimer states, which then constituted the basis for the digestion studies. 35151483 3 86 theme in 545:546 arg1 model 571:575 the INFOGEST 2.0 in vitro static digestion model 528:575 the INFOGEST 2.0 in vitro static digestion model 528:575 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 0 87 theme purified 73:80 arg1 κ-casein 82:89 purified κ-casein 73:89 purified κ-casein 73:89 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein. 35151483 2 88 from contributions 262:274 arg1 process 351:357 the in vitro digestion process 328:357 the in vitro digestion process of κ-CN 328:365 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35151483 4 89 theme terminal 620:627 arg1 acids 636:640 the terminal sialic acids 616:640 the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants 616:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 6 90 gly desialylated 968:979 arg1 isolates 986:993 native and desialylated κ-CN isolates 957:993 native and desialylated κ-CN isolates 957:993 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 4 91 theme purified 690:697 arg1 variants 724:731 the purified κ-CN A, B, and E protein variants 686:731 the purified κ-CN A, B, and E protein variants 686:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 6 92 theme native 957:962 arg1 isolates 986:993 native and desialylated κ-CN isolates 957:993 native and desialylated κ-CN isolates 957:993 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 9 93 theme variant 1650:1656 arg1 B 1658:1658 variant B 1650:1658 variant B 1650:1658 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 10 94 theme enhanced 2087:2094 arg1 digestibility 2096:2108 enhanced digestibility 2087:2108 enhanced digestibility 2087:2108 This finding could be applied to produce dairy products with enhanced digestibility. 35151483 4 95 theme A 704:704 arg1 variants 724:731 the purified κ-CN A, B, and E protein variants 686:731 the purified κ-CN A, B, and E protein variants 686:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 8 96 theme digestion 1408:1416 arg1 rates 1418:1422 faster in vitro digestion rates 1392:1422 faster in vitro digestion rates in both gastric and intestinal phases 1392:1460 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 9 97 theme glycosylation 1862:1874 arg1 degree 1876:1881 low glycosylation degree 1858:1881 low glycosylation degree of purified κ-CN 1858:1898 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 4 98 theme O-linked 657:664 arg1 oligosaccharides 666:681 the O-linked oligosaccharides 653:681 the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants 653:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 2 99 theme digestion 341:349 arg1 process 351:357 the in vitro digestion process 328:357 the in vitro digestion process of κ-CN 328:365 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35151483 0 100 theme variants 19:26 arg1 Effects 0:6 Effects 0:6 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein 0:89 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein. 35151483 8 101 dep variants 1353:1360 arg1 variants 1353:1360 purified variants A and E 1344:1368 purified variants A and E 1344:1368 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 8 101 dep variants 1353:1360 arg1 E 1368:1368 E 1368:1368 E 1368:1368 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 8 101 dep variants 1353:1360 arg1 A 1362:1362 A 1362:1362 A 1362:1362 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 5 102 theme variants 872:879 arg1 purities 860:867 purities 860:867 purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively 860:930 The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. 35151483 0 103 theme sialylation 32:42 arg1 Effects 0:6 Effects 0:6 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein 0:89 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein. 35151483 0 104 dep in 47:48 arg1 vitro 50:54 vitro 50:54 vitro 50:54 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein. 35151483 8 105 theme gastric 1432:1438 arg1 phases 1455:1460 both gastric and intestinal phases 1427:1460 both gastric and intestinal phases 1427:1460 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 9 106 theme κ-CN 1895:1898 arg1 degree 1876:1881 low glycosylation degree 1858:1881 low glycosylation degree of purified κ-CN 1858:1898 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 4 107 theme protein 716:722 arg1 variants 724:731 the purified κ-CN A, B, and E protein variants 686:731 the purified κ-CN A, B, and E protein variants 686:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 3 108 theme homozygous 422:431 arg1 cows 433:436 homozygous cows 422:436 homozygous cows with κ-CN phenotypes AA, BB, or EE 422:471 Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. 35151483 0 109 theme in 47:48 arg1 digestibility 56:68 in vitro digestibility 47:68 in vitro digestibility of purified κ-casein 47:89 Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein. 35151483 6 110 theme intestinal 1010:1019 arg1 phases 1021:1026 gastric and intestinal phases 998:1026 gastric and intestinal phases 998:1026 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 8 111 theme intestinal 1444:1453 arg1 phases 1455:1460 both gastric and intestinal phases 1427:1460 both gastric and intestinal phases 1427:1460 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 2 112 theme related 305:311 arg1 sialylation 313:323 its related sialylation 301:323 its related sialylation 301:323 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35151483 6 113 theme gastric 998:1004 arg1 phases 1021:1026 gastric and intestinal phases 998:1026 gastric and intestinal phases 998:1026 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 2 114 dep in 332:333 arg1 vitro 335:339 vitro 335:339 vitro 335:339 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35151483 4 115 theme B 707:707 arg1 variants 724:731 the purified κ-CN A, B, and E protein variants 686:731 the purified κ-CN A, B, and E protein variants 686:731 Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. 35151483 9 116 gly desialylation 1951:1963 arg1 oligosaccharides 1981:1996 the O-linked oligosaccharides 1968:1996 the O-linked oligosaccharides 1968:1996 In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. 35151483 8 117 theme digestion 1539:1547 arg1 rates 1549:1553 both gastric and intestinal digestion rates 1511:1553 both gastric and intestinal digestion rates for all variants 1511:1570 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 8 118 dep faster 1392:1397 arg1 in 1399:1400 in 1399:1400 in 1399:1400 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 6 119 theme isolates 986:993 arg1 degradations 941:952 Protein degradations 933:952 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases 933:1026 Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. 35151483 8 120 theme variant 1476:1482 arg1 Desialylation 1487:1499 variant B. Desialylation 1476:1499 variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH 1476:1589 As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. 35151483 2 121 theme in 332:333 arg1 process 351:357 the in vitro digestion process 328:357 the in vitro digestion process of κ-CN 328:365 Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. 35392915 7 0 theme siCPT1 1409:1414 arg1 responses 1454:1462 siCPT1 dampened PPARγ agonists-promoted Treg responses 1409:1462 siCPT1 dampened PPARγ agonists-promoted Treg responses 1409:1462 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 2 1 theme metabolism 357:366 arg1 view 340:343 view 340:343 view of cellular metabolism 340:366 This study aimed to solve this problem in view of cellular metabolism. 35392915 6 2 theme CTLA4 1151:1155 arg1 transcription 1120:1132 the transcription 1116:1132 the transcription of Foxp3, IL-10, CTLA4 and TIGIT 1116:1165 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 10 3 theme N-linked 1988:1995 arg1 glycosylation 1997:2009 N-linked glycosylation 1988:2009 N-linked glycosylation 1988:2009 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 35392915 12 4 theme antagonist 2318:2327 arg1 GW9662 2329:2334 PPARγ antagonist GW9662 2312:2334 PPARγ antagonist GW9662 2312:2334 Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. 35392915 13 5 theme PPARγ 2506:2510 arg1 activation 2492:2501 The activation 2488:2501 The activation of PPARγ 2488:2510 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 12 6 theme 15d-PGJ2 2420:2427 arg1 effects 2394:2400 the effects 2390:2400 the effects of rosiglitazone, 15d-PGJ2 and morin 2390:2437 Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. 35392915 6 7 theme IL-10 1144:1148 arg1 transcription 1120:1132 the transcription 1116:1132 the transcription of Foxp3, IL-10, CTLA4 and TIGIT 1116:1165 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 11 8 theme CD36 2211:2214 arg1 abundance 2198:2206 the increased surface abundance 2176:2206 the increased surface abundance of CD36 2176:2214 However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. 35392915 11 8 theme CD36 2211:2214 arg1 owing 2246:2250 owing 2246:2250 owing 2246:2250 However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. 35392915 4 9 theme oxygen 628:633 arg1 rate 647:650 oxygen consumption rate 628:650 oxygen consumption rate 628:650 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 13 10 theme autoimmune 2690:2699 arg1 diseases 2701:2708 autoimmune diseases 2690:2708 autoimmune diseases 2690:2708 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 6 11 theme Foxp3 1137:1141 arg1 transcription 1120:1132 the transcription 1116:1132 the transcription of Foxp3, IL-10, CTLA4 and TIGIT 1116:1165 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 12 12 theme exact 2455:2459 arg1 role 2461:2464 the exact role 2451:2464 the exact role of PPARγ 2451:2473 Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. 35392915 4 13 theme rate 647:650 arg1 detection 596:604 the detection 592:604 the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level 592:725 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 6 14 theme Treg 1200:1203 arg1 cells 1205:1209 Treg cells 1200:1209 Treg cells 1200:1209 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 9 15 theme agonists-promoted 1824:1840 arg1 FAO 1842:1844 PPARγ agonists-promoted FAO 1818:1844 PPARγ agonists-promoted FAO 1818:1844 Notably, the enzyme activity of phosphofructokinase (PFK) was inhibited by PPARγ agonists and the effect was limited by siCD36 or siCPT1, implying PFK to be a link between PPARγ agonists-promoted FAO and UDP-GlcNAc biosynthesis aside from acetyl-CoA. 35392915 4 16 theme fatty 609:613 arg1 uptake 620:625 fatty acid uptake 609:625 fatty acid uptake 609:625 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 12 17 theme morin 2433:2437 arg1 effects 2394:2400 the effects 2390:2400 the effects of rosiglitazone, 15d-PGJ2 and morin 2390:2437 Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. 35392915 4 18 theme uptake 620:625 arg1 detection 596:604 the detection 592:604 the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level 592:725 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 0 19 theme TβRII/IL-2Rα 147:158 arg1 branching 134:142 subsequent N-glycan branching 114:142 subsequent N-glycan branching of TβRII/IL-2Rα 114:158 The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. 35392915 0 19 theme TβRII/IL-2Rα 147:158 arg1 oxidation 100:108 CD36/CPT1-mediated fatty acid oxidation 70:108 CD36/CPT1-mediated fatty acid oxidation 70:108 The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. 35392915 5 20 theme PPARγ 808:812 arg1 role 800:803 the exact role 790:803 the exact role of PPARγ in the action of PPARγ agonists 790:844 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 5 20 theme PPARγ 808:812 arg1 involvement 732:742 The involvement 728:742 The involvement of UDP-GlcNAc/N-linked glycosylation axis 728:784 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 5 21 theme PPARγ 831:835 arg1 agonists 837:844 PPARγ agonists 831:844 PPARγ agonists 831:844 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 10 22 theme N-linked 2096:2103 arg1 glycosylation 2105:2117 N-linked glycosylation 2096:2117 N-linked glycosylation 2096:2117 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 35392915 4 23 theme membrane 687:694 arg1 potential 696:704 mitochondrial membrane potential 673:704 mitochondrial membrane potential 673:704 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 5 24 theme western 888:894 arg1 blotting 896:903 western blotting 888:903 western blotting 888:903 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 7 25 theme CPT1 1314:1317 arg1 levels 1295:1300 the levels 1291:1300 the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses 1291:1462 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 5 26 from involvement 732:742 arg1 action 821:826 the action 817:826 the action of PPARγ agonists 817:844 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 11 27 theme overall 2283:2289 arg1 expression 2291:2300 agonists-up-regulated overall expression 2261:2300 agonists-up-regulated overall expression 2261:2300 However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. 35392915 7 28 theme CD36 1305:1308 arg1 levels 1295:1300 the levels 1291:1300 the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses 1291:1462 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 4 29 theme mitochondrial 653:665 arg1 mass 667:670 mitochondrial mass 653:670 mitochondrial mass 653:670 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 1 30 theme Peroxisome 172:181 arg1 PPARγ 222:226 PPARγ 222:226 PPARγ 222:226 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 1 30 theme Peroxisome 172:181 arg1 gamma 215:219 BACKGROUND Peroxisome proliferator-activated receptor gamma 161:219 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) 161:227 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 1 30 theme Peroxisome 172:181 arg1 enhancer 235:242 an enhancer 232:242 an enhancer of Treg responses 232:260 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 9 31 theme phosphofructokinase 1678:1696 arg1 activity 1666:1673 the enzyme activity 1655:1673 the enzyme activity of phosphofructokinase (PFK) 1655:1702 Notably, the enzyme activity of phosphofructokinase (PFK) was inhibited by PPARγ agonists and the effect was limited by siCD36 or siCPT1, implying PFK to be a link between PPARγ agonists-promoted FAO and UDP-GlcNAc biosynthesis aside from acetyl-CoA. 35392915 0 32 theme fatty 89:93 arg1 oxidation 100:108 CD36/CPT1-mediated fatty acid oxidation 70:108 CD36/CPT1-mediated fatty acid oxidation 70:108 The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. 35392915 1 33 theme receptor 206:213 arg1 PPARγ 222:226 PPARγ 222:226 PPARγ 222:226 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 1 33 theme receptor 206:213 arg1 gamma 215:219 BACKGROUND Peroxisome proliferator-activated receptor gamma 161:219 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) 161:227 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 1 33 theme receptor 206:213 arg1 enhancer 235:242 an enhancer 232:242 an enhancer of Treg responses 232:260 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 6 34 theme RESULTS 978:984 arg1 Rosiglitazone 986:998 RESULTS Rosiglitazone 978:998 RESULTS Rosiglitazone 978:998 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 3 35 dep agonists 400:407 arg1 agonist 420:426 synthetic agonist 410:426 synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin 410:494 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 10 36 theme surface 1946:1952 arg1 abundance 1954:1962 the cell surface abundance 1937:1962 the cell surface abundance of TβRII and IL-2Rα 1937:1982 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 35392915 0 37 theme subsequent 114:123 arg1 branching 134:142 subsequent N-glycan branching 114:142 subsequent N-glycan branching of TβRII/IL-2Rα 114:158 The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. 35392915 5 38 from role 800:803 arg1 action 821:826 the action 817:826 the action of PPARγ agonists 817:844 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 0 39 theme Treg 33:36 arg1 responses 38:46 Treg responses 33:46 Treg responses 33:46 The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. 35392915 6 40 theme Treg 1062:1065 arg1 cells 1067:1071 CD4+Foxp3+ Treg cells 1051:1071 CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells 1051:1105 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 12 41 theme rosiglitazone 2405:2417 arg1 effects 2394:2400 the effects 2390:2400 the effects of rosiglitazone, 15d-PGJ2 and morin 2390:2437 Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. 35392915 4 42 theme level 721:725 arg1 detection 596:604 the detection 592:604 the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level 592:725 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 13 43 theme CD36/CPT1-mediated 2558:2575 arg1 oxidation 2588:2596 CD36/CPT1-mediated fatty acid oxidation 2558:2596 CD36/CPT1-mediated fatty acid oxidation 2558:2596 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 5 44 theme commercial 908:917 arg1 kit 919:921 a commercial kit 906:921 a commercial kit for enzyme activity 906:941 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 8 45 theme PPARγ 1475:1479 arg1 agonists 1481:1488 PPARγ agonists 1475:1488 PPARγ agonists 1475:1488 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 3 46 theme natural 473:479 arg1 product 481:487 natural product 473:487 synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin 410:494 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 13 47 theme acid 2583:2586 arg1 oxidation 2588:2596 CD36/CPT1-mediated fatty acid oxidation 2558:2596 CD36/CPT1-mediated fatty acid oxidation 2558:2596 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 1 48 theme BACKGROUND 161:170 arg1 PPARγ 222:226 PPARγ 222:226 PPARγ 222:226 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 1 48 theme BACKGROUND 161:170 arg1 gamma 215:219 BACKGROUND Peroxisome proliferator-activated receptor gamma 161:219 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) 161:227 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 1 48 theme BACKGROUND 161:170 arg1 enhancer 235:242 an enhancer 232:242 an enhancer of Treg responses 232:260 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 4 49 theme acid 549:552 arg1 FAO 565:567 FAO 565:567 FAO 565:567 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 4 49 theme acid 549:552 arg1 oxidation 554:562 The fatty acid oxidation 539:562 The fatty acid oxidation (FAO) 539:568 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 13 50 theme Treg 2521:2524 arg1 responses 2526:2534 Treg responses 2521:2534 Treg responses 2521:2534 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 7 51 theme Treg 1263:1266 arg1 cells 1268:1272 differentiating Treg cells 1247:1272 differentiating Treg cells 1247:1272 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 3 52 theme synthetic 410:418 arg1 agonist 420:426 synthetic agonist 410:426 synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin 410:494 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 2 53 theme cellular 348:355 arg1 metabolism 357:366 cellular metabolism 348:366 cellular metabolism 348:366 This study aimed to solve this problem in view of cellular metabolism. 35392915 5 54 theme exact 794:798 arg1 role 800:803 the exact role 790:803 the exact role of PPARγ in the action of PPARγ agonists 790:844 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 7 55 theme agonists-promoted 1431:1447 arg1 responses 1454:1462 siCPT1 dampened PPARγ agonists-promoted Treg responses 1409:1462 siCPT1 dampened PPARγ agonists-promoted Treg responses 1409:1462 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 8 56 theme subsequent 1527:1536 arg1 glycosylation 1547:1559 subsequent N-linked glycosylation 1527:1559 subsequent N-linked glycosylation 1527:1559 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 1 57 theme Treg 247:250 arg1 responses 252:260 Treg responses 247:260 Treg responses 247:260 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 7 58 theme dampened 1416:1423 arg1 responses 1454:1462 siCPT1 dampened PPARγ agonists-promoted Treg responses 1409:1462 siCPT1 dampened PPARγ agonists-promoted Treg responses 1409:1462 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 6 59 theme T 1099:1099 arg1 cells 1101:1105 naïve CD4+ T cells 1088:1105 naïve CD4+ T cells 1088:1105 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 8 60 theme branching 1609:1617 arg1 Mgat1 1627:1631 N-glycan branching enzymes Mgat1 1600:1631 N-glycan branching enzymes Mgat1 1600:1631 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 6 61 theme naïve 1088:1092 arg1 cells 1101:1105 naïve CD4+ T cells 1088:1105 naïve CD4+ T cells 1088:1105 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 12 62 theme PPARγ 2469:2473 arg1 role 2461:2464 the exact role 2451:2464 the exact role of PPARγ 2451:2473 Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. 35392915 5 63 theme UDP-GlcNAc/N-linked 747:765 arg1 axis 781:784 UDP-GlcNAc/N-linked glycosylation axis 747:784 UDP-GlcNAc/N-linked glycosylation axis 747:784 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 8 64 theme Mgat1 1627:1631 arg1 5 1643:1643 5 1643:1643 5 1643:1643 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 8 64 theme Mgat1 1627:1631 arg1 4 1637:1637 4 1637:1637 4 1637:1637 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 8 64 theme Mgat1 1627:1631 arg1 2 1634:1634 2 1634:1634 2 1634:1634 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 8 64 theme Mgat1 1627:1631 arg1 expressions 1585:1595 the expressions 1581:1595 the expressions of N-glycan branching enzymes Mgat1 1581:1631 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 11 65 theme agonists-up-regulated 2261:2281 arg1 expression 2291:2300 agonists-up-regulated overall expression 2261:2300 agonists-up-regulated overall expression 2261:2300 However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. 35392915 13 66 theme TβRII/IL-2Rα 2635:2646 arg1 oxidation 2588:2596 CD36/CPT1-mediated fatty acid oxidation 2558:2596 CD36/CPT1-mediated fatty acid oxidation 2558:2596 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 13 66 theme TβRII/IL-2Rα 2635:2646 arg1 branching 2622:2630 subsequent N-glycan branching 2602:2630 subsequent N-glycan branching of TβRII/IL-2Rα 2602:2646 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 8 67 link N-linked 1538:1545 arg1 glycosylation 1547:1559 subsequent N-linked glycosylation 1527:1559 subsequent N-linked glycosylation 1527:1559 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 10 68 theme IL-2/STAT5 2047:2056 arg1 signaling 2058:2066 IL-2/STAT5 signaling 2047:2066 IL-2/STAT5 signaling 2047:2066 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 35392915 12 69 theme PPARγ 2312:2316 arg1 GW9662 2329:2334 PPARγ antagonist GW9662 2312:2334 PPARγ antagonist GW9662 2312:2334 Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. 35392915 5 70 theme agonists 837:844 arg1 action 821:826 the action 817:826 the action of PPARγ agonists 817:844 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 10 71 link N-linked 1988:1995 arg1 glycosylation 1997:2009 N-linked glycosylation 1988:2009 N-linked glycosylation 1988:2009 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 35392915 11 72 theme surface 2190:2196 arg1 abundance 2198:2206 the increased surface abundance 2176:2206 the increased surface abundance of CD36 2176:2214 However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. 35392915 11 72 theme surface 2190:2196 arg1 owing 2246:2250 owing 2246:2250 owing 2246:2250 However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. 35392915 5 73 theme glycosylation 767:779 arg1 axis 781:784 UDP-GlcNAc/N-linked glycosylation axis 747:784 UDP-GlcNAc/N-linked glycosylation axis 747:784 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 6 74 theme cells 1205:1209 arg1 function 1188:1195 the function 1184:1195 the function of Treg cells 1184:1209 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 5 75 link UDP-GlcNAc/N-linked 747:765 arg1 axis 781:784 UDP-GlcNAc/N-linked glycosylation axis 747:784 UDP-GlcNAc/N-linked glycosylation axis 747:784 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 6 76 theme TIGIT 1161:1165 arg1 transcription 1120:1132 the transcription 1116:1132 the transcription of Foxp3, IL-10, CTLA4 and TIGIT 1116:1165 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 7 77 from FAO 1240:1242 arg1 cells 1268:1272 differentiating Treg cells 1247:1272 differentiating Treg cells 1247:1272 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 9 78 theme PPARγ 1818:1822 arg1 FAO 1842:1844 PPARγ agonists-promoted FAO 1818:1844 PPARγ agonists-promoted FAO 1818:1844 Notably, the enzyme activity of phosphofructokinase (PFK) was inhibited by PPARγ agonists and the effect was limited by siCD36 or siCPT1, implying PFK to be a link between PPARγ agonists-promoted FAO and UDP-GlcNAc biosynthesis aside from acetyl-CoA. 35392915 4 79 theme consumption 635:645 arg1 rate 647:650 oxygen consumption rate 628:650 oxygen consumption rate 628:650 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 14 80 dep Abstract 2717:2724 arg1 Video 2711:2715 Video 2711:2715 Video 2711:2715 Video Abstract. 35392915 9 81 theme UDP-GlcNAc 1850:1859 arg1 biosynthesis 1861:1872 UDP-GlcNAc biosynthesis 1850:1872 UDP-GlcNAc biosynthesis 1850:1872 Notably, the enzyme activity of phosphofructokinase (PFK) was inhibited by PPARγ agonists and the effect was limited by siCD36 or siCPT1, implying PFK to be a link between PPARγ agonists-promoted FAO and UDP-GlcNAc biosynthesis aside from acetyl-CoA. 35392915 4 82 theme acid 615:618 arg1 uptake 620:625 fatty acid uptake 609:625 fatty acid uptake 609:625 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 7 83 theme other 1327:1331 arg1 enzymes 1333:1339 other enzymes 1327:1339 the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses 1291:1462 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 4 84 theme mitochondrial 673:685 arg1 potential 696:704 mitochondrial membrane potential 673:704 mitochondrial membrane potential 673:704 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 9 85 theme enzyme 1659:1664 arg1 activity 1666:1673 the enzyme activity 1655:1673 the enzyme activity of phosphofructokinase (PFK) 1655:1702 Notably, the enzyme activity of phosphofructokinase (PFK) was inhibited by PPARγ agonists and the effect was limited by siCD36 or siCPT1, implying PFK to be a link between PPARγ agonists-promoted FAO and UDP-GlcNAc biosynthesis aside from acetyl-CoA. 35392915 4 86 theme potential 696:704 arg1 detection 596:604 the detection 592:604 the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level 592:725 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 0 87 theme CD36/CPT1-mediated 70:87 arg1 oxidation 100:108 CD36/CPT1-mediated fatty acid oxidation 70:108 CD36/CPT1-mediated fatty acid oxidation 70:108 The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. 35392915 5 88 theme flow 865:868 arg1 cytometry 870:878 flow cytometry 865:878 flow cytometry 865:878 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 10 89 theme Treg 2123:2126 arg1 responses 2128:2136 Treg responses 2123:2136 Treg responses 2123:2136 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 35392915 10 90 theme PPARγ 1910:1914 arg1 agonists 1916:1923 PPARγ agonists 1910:1923 PPARγ agonists 1910:1923 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 35392915 0 91 theme acid 95:98 arg1 oxidation 100:108 CD36/CPT1-mediated fatty acid oxidation 70:108 CD36/CPT1-mediated fatty acid oxidation 70:108 The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. 35392915 1 92 theme proliferator-activated 183:204 arg1 PPARγ 222:226 PPARγ 222:226 PPARγ 222:226 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 1 92 theme proliferator-activated 183:204 arg1 gamma 215:219 BACKGROUND Peroxisome proliferator-activated receptor gamma 161:219 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) 161:227 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 1 92 theme proliferator-activated 183:204 arg1 enhancer 235:242 an enhancer 232:242 an enhancer of Treg responses 232:260 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 10 93 link N-linked 2096:2103 arg1 glycosylation 2105:2117 N-linked glycosylation 2096:2117 N-linked glycosylation 2096:2117 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 35392915 4 94 theme mass 667:670 arg1 detection 596:604 the detection 592:604 the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level 592:725 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 5 95 theme enzyme 927:932 arg1 activity 934:941 enzyme activity 927:941 enzyme activity 927:941 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 11 96 theme increased 2180:2188 arg1 abundance 2198:2206 the increased surface abundance 2176:2206 the increased surface abundance of CD36 2176:2214 However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. 35392915 11 96 theme increased 2180:2188 arg1 owing 2246:2250 owing 2246:2250 owing 2246:2250 However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. 35392915 10 97 theme cell 1941:1944 arg1 abundance 1954:1962 the cell surface abundance 1937:1962 the cell surface abundance of TβRII and IL-2Rα 1937:1982 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 35392915 0 98 theme N-glycan 125:132 arg1 branching 134:142 subsequent N-glycan branching 114:142 subsequent N-glycan branching of TβRII/IL-2Rα 114:158 The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. 35392915 6 99 theme cells 1067:1071 arg1 frequency 1038:1046 the frequency 1034:1046 the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells 1034:1105 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 3 100 dep agonist 420:426 arg1 ligand 455:460 endogenous ligand 444:460 synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin 410:494 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 3 100 dep agonist 420:426 arg1 rosiglitazone 429:441 rosiglitazone 429:441 synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin 410:494 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 3 100 dep agonist 420:426 arg1 morin 490:494 morin 490:494 synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin 410:494 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 3 100 dep agonist 420:426 arg1 15d-PGJ2 463:470 15d-PGJ2 463:470 synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin 410:494 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 3 100 dep agonist 420:426 arg1 product 481:487 natural product 473:487 synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin 410:494 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 13 101 theme subsequent 2602:2611 arg1 branching 2622:2630 subsequent N-glycan branching 2602:2630 subsequent N-glycan branching of TβRII/IL-2Rα 2602:2646 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 6 102 theme CD4+Foxp3+ 1051:1060 arg1 cells 1067:1071 CD4+Foxp3+ Treg cells 1051:1071 CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells 1051:1105 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 9 103 theme PPARγ 1721:1725 arg1 agonists 1727:1734 PPARγ agonists 1721:1734 PPARγ agonists 1721:1734 Notably, the enzyme activity of phosphofructokinase (PFK) was inhibited by PPARγ agonists and the effect was limited by siCD36 or siCPT1, implying PFK to be a link between PPARγ agonists-promoted FAO and UDP-GlcNAc biosynthesis aside from acetyl-CoA. 35392915 4 104 theme fatty 543:547 arg1 FAO 565:567 FAO 565:567 FAO 565:567 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 4 104 theme fatty 543:547 arg1 oxidation 554:562 The fatty acid oxidation 539:562 The fatty acid oxidation (FAO) 539:568 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 4 105 theme acetyl-CoA 710:719 arg1 level 721:725 acetyl-CoA level 710:725 acetyl-CoA level 710:725 The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. 35392915 3 106 theme endogenous 444:453 arg1 ligand 455:460 endogenous ligand 444:460 synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin 410:494 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 0 107 theme PPARγ 18:22 arg1 activation 4:13 The activation 0:13 The activation of PPARγ 0:22 The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. 35392915 8 108 theme UDP-GlcNAc 1499:1508 arg1 biosynthesis 1510:1521 UDP-GlcNAc biosynthesis 1499:1521 UDP-GlcNAc biosynthesis 1499:1521 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 5 109 theme axis 781:784 arg1 role 800:803 the exact role 790:803 the exact role of PPARγ in the action of PPARγ agonists 790:844 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 5 109 theme axis 781:784 arg1 involvement 732:742 The involvement 728:742 The involvement of UDP-GlcNAc/N-linked glycosylation axis 728:784 The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. 35392915 7 110 theme differentiating 1247:1261 arg1 cells 1268:1272 differentiating Treg cells 1247:1272 differentiating Treg cells 1247:1272 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 13 111 dep CONCLUSIONS 2476:2486 arg1 enhances 2512:2519 enhances 2512:2519 enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases 2512:2708 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 12 112 theme PPARγ 2372:2376 arg1 GW9662 2329:2334 PPARγ antagonist GW9662 2312:2334 PPARγ antagonist GW9662 2312:2334 Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. 35392915 13 113 theme N-glycan 2613:2620 arg1 branching 2622:2630 subsequent N-glycan branching 2602:2630 subsequent N-glycan branching of TβRII/IL-2Rα 2602:2646 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 8 114 theme N-linked 1538:1545 arg1 glycosylation 1547:1559 subsequent N-linked glycosylation 1527:1559 subsequent N-linked glycosylation 1527:1559 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 8 115 theme N-glycan 1600:1607 arg1 Mgat1 1627:1631 N-glycan branching enzymes Mgat1 1600:1631 N-glycan branching enzymes Mgat1 1600:1631 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 13 116 theme fatty 2577:2581 arg1 oxidation 2588:2596 CD36/CPT1-mediated fatty acid oxidation 2558:2596 CD36/CPT1-mediated fatty acid oxidation 2558:2596 CONCLUSIONS The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. 35392915 7 117 theme Treg 1449:1452 arg1 responses 1454:1462 siCPT1 dampened PPARγ agonists-promoted Treg responses 1409:1462 siCPT1 dampened PPARγ agonists-promoted Treg responses 1409:1462 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 10 118 theme IL-2Rα 1977:1982 arg1 abundance 1954:1962 the cell surface abundance 1937:1962 the cell surface abundance of TβRII and IL-2Rα 1937:1982 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 35392915 3 119 used used 502:505 arg2 tools 514:518 the tools 510:518 the tools 510:518 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 3 119 used used 502:505 arg2 METHODS 369:375 METHODS Three 369:381 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) 369:495 METHODS Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. 35392915 8 120 theme enzymes 1619:1625 arg1 Mgat1 1627:1631 N-glycan branching enzymes Mgat1 1600:1631 N-glycan branching enzymes Mgat1 1600:1631 Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. 35392915 1 121 theme responses 252:260 arg1 gamma 215:219 BACKGROUND Peroxisome proliferator-activated receptor gamma 161:219 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) 161:227 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 1 121 theme responses 252:260 arg1 enhancer 235:242 an enhancer 232:242 an enhancer of Treg responses 232:260 BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. 35392915 7 122 theme PPARγ 1425:1429 arg1 responses 1454:1462 siCPT1 dampened PPARγ agonists-promoted Treg responses 1409:1462 siCPT1 dampened PPARγ agonists-promoted Treg responses 1409:1462 They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. 35392915 6 123 theme CD4+ 1094:1097 arg1 cells 1101:1105 naïve CD4+ T cells 1088:1105 naïve CD4+ T cells 1088:1105 RESULTS Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. 35392915 10 124 theme TβRII 1967:1971 arg1 abundance 1954:1962 the cell surface abundance 1937:1962 the cell surface abundance of TβRII and IL-2Rα 1937:1982 Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. 37107083 7 0 theme Chamaemelum 1114:1124 arg1 EO 1133:1134 Chamaemelum nobile EO 1114:1134 Chamaemelum nobile EO 1114:1134 In Chamaemelum nobile EO, the most abundant compound is angelylangelate (41.79%). 37107083 10 1 theme atlantica 1356:1364 arg1 β-himachalene 1369:1381 β-himachalene 1369:1381 β-himachalene 1369:1381 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 10 1 theme atlantica 1356:1364 arg1 compound 1337:1344 The main compound 1328:1344 The main compound of Cedrus atlantica 1328:1364 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 10 1 theme atlantica 1356:1364 arg1 % 1389:1389 40.19% 1384:1389 40.19% 1384:1389 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 3 2 theme Clevenger-type 662:675 arg1 apparatus 677:685 a Clevenger-type apparatus 660:685 a Clevenger-type apparatus 660:685 The essential oils were extracted by hydrodistillation in a Clevenger-type apparatus. 37107083 0 3 with Plants 87:92 arg1 Properties 108:117 Cosmetic Properties 99:117 Cosmetic Properties 99:117 Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties. 37107083 8 4 from rich 1223:1226 arg1 % 1246:1246 29.01% 1241:1246 29.01% 1241:1246 The EO of Citrus aurantium is rich in linalool (29.01%). 37107083 8 4 from rich 1223:1226 arg1 linalool 1231:1238 linalool 1231:1238 linalool (29.01%) 1231:1247 The EO of Citrus aurantium is rich in linalool (29.01%). 37107083 1 5 theme species-Laurus 239:252 arg1 nobilis 254:260 six species-Laurus nobilis 235:260 six species-Laurus nobilis 235:260 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 13 6 theme Citrus 2344:2349 arg1 EO 2361:2362 then Citrus aurantium EO 2339:2362 then Citrus aurantium EO (14.70%) 2339:2371 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 13 6 theme Citrus 2344:2349 arg1 % 2370:2370 14.70% 2365:2370 14.70% 2365:2370 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 11 7 from rich 1720:1723 arg1 monoterpenes 1739:1750 oxygenated monoterpenes 1728:1750 oxygenated monoterpenes 1728:1750 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 13 8 theme Cedrus 2278:2283 arg1 % 2304:2304 62.38% 2299:2304 62.38% 2299:2304 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 13 8 theme Cedrus 2278:2283 arg1 EO 2295:2296 Cedrus atlantica EO 2278:2296 Cedrus atlantica EO (62.38%) 2278:2305 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 9 9 theme lentiscus 1269:1277 arg1 EO 1254:1255 The EO 1250:1255 The EO of Pistacia lentiscus 1250:1277 The EO of Pistacia lentiscus is dominated by 3-methylpentylangelate (27.83%). 37107083 6 10 theme nobilis 1057:1063 arg1 EO 1044:1045 the EO 1040:1045 the EO of Laurus nobilis 1040:1063 Indeed, in the EO of Laurus nobilis, 1,8-cineole (36.58%) is the major component. 37107083 11 11 from gathers 1857:1863 arg1 rich 1819:1822 rich 1819:1822 rich 1819:1822 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 13 12 dep EO 2295:2296 arg1 EO 2361:2362 then Citrus aurantium EO 2339:2362 then Citrus aurantium EO (14.70%) 2339:2371 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 13 12 dep EO 2295:2296 arg1 % 2370:2370 14.70% 2365:2370 14.70% 2365:2370 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 13 13 theme lentiscus 2194:2202 arg1 EOs 2159:2161 The EOs 2155:2161 The EOs of Laurus nobilis and Pistacia lentiscus 2155:2202 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 5 14 located detected 958:965 arg2 composition 946:956 the chemical composition 933:956 the chemical composition detected at the level of the majority compounds between these species 933:1026 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 5 14 located detected 958:965 arg1 level 974:978 the level 970:978 the level of the majority compounds between these species 970:1026 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 12 15 theme activity 2054:2061 arg1 study 2029:2033 The study 2025:2033 The study of the antioxidant activity 2025:2061 The study of the antioxidant activity showed that all the EOs tested have a high capacity for scavenging free radicals from DPPH. 37107083 14 16 theme fungal 2453:2458 arg1 strains 2460:2466 eight fungal strains 2447:2466 eight fungal strains 2447:2466 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 10 17 theme flowers 1425:1431 arg1 EO 1403:1404 the EO 1399:1404 the EO of Rosa damascenaa flowers 1399:1431 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 10 17 theme flowers 1425:1431 arg1 rich 1436:1439 rich 1436:1439 rich 1436:1439 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 12 18 from DPPH 2149:2152 arg1 radicals 2135:2142 scavenging free radicals 2119:2142 scavenging free radicals from DPPH 2119:2152 The study of the antioxidant activity showed that all the EOs tested have a high capacity for scavenging free radicals from DPPH. 37107083 5 19 theme majority 987:994 arg1 compounds 996:1004 the majority compounds 983:1004 the majority compounds between these species 983:1026 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 1 20 theme oils 221:224 arg1 activities 193:202 antioxidant and antimicrobial activities 163:202 activities 193:202 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 20 theme oils 221:224 arg1 composition 147:157 chemical composition 138:157 chemical composition 138:157 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 14 21 theme bactericidal 2517:2528 arg1 activities 2545:2554 significant bactericidal and fungicidal activities 2505:2554 significant bactericidal and fungicidal activities 2505:2554 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 10 22 theme Rosa 1409:1412 arg1 flowers 1425:1431 Rosa damascenaa flowers 1409:1431 Rosa damascenaa flowers 1409:1431 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 2 23 theme metabolites 546:556 arg1 presence 430:437 the presence 426:437 the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages 426:599 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 14 24 theme bacterial 2425:2433 arg1 strains 2435:2441 eight bacterial strains 2419:2441 eight bacterial strains 2419:2441 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 11 25 theme plants 1521:1526 arg1 EOs 1510:1512 the EOs 1506:1512 the EOs of the plants studied by ACH and ACP 1506:1549 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 10 26 dep β-himachalene 1369:1381 arg1 β-himachalene 1369:1381 β-himachalene 1369:1381 β-himachalene 1369:1381 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 10 26 dep β-himachalene 1369:1381 arg1 % 1389:1389 40.19% 1384:1389 40.19% 1384:1389 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 10 26 dep β-himachalene 1369:1381 arg1 compound 1337:1344 The main compound 1328:1344 The main compound of Cedrus atlantica 1328:1364 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 11 27 theme oxygenated 1728:1737 arg1 monoterpenes 1739:1750 oxygenated monoterpenes 1728:1750 oxygenated monoterpenes 1728:1750 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 11 28 theme oxygenated 1944:1953 arg1 sesquiterpenes 1955:1968 oxygenated sesquiterpenes 1944:1968 oxygenated sesquiterpenes 1944:1968 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 13 29 theme Chamaemelum 2311:2321 arg1 nobile 2323:2328 Chamaemelum nobile 2311:2328 Chamaemelum nobile (47.98%) 2311:2337 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 13 29 theme Chamaemelum 2311:2321 arg1 % 2336:2336 47.98% 2331:2336 47.98% 2331:2336 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 5 30 theme compounds 832:840 arg1 presence 811:818 the presence 807:818 the presence of 30 to 35 compounds 807:840 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 14 31 theme significant 2505:2515 arg1 activities 2545:2554 significant bactericidal and fungicidal activities 2505:2554 significant bactericidal and fungicidal activities 2505:2554 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 0 32 theme Medicinal 77:85 arg1 Plants 87:92 Six Aromatic Medicinal Plants 64:92 Six Aromatic Medicinal Plants with Cosmetic Properties 64:117 Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties. 37107083 13 33 dep Cedrus 2278:2283 arg1 atlantica 2285:2293 atlantica 2285:2293 atlantica 2285:2293 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 15 34 theme rich 2747:2750 arg1 EOs 2743:2745 these EOs 2737:2745 these EOs rich in antimicrobial and antioxidant components 2737:2794 Thus, these EOs rich in antimicrobial and antioxidant components can serve as a natural alternative; this confirms their use as additives in cosmetics. 37107083 15 34 theme rich 2747:2750 arg1 alternative 2819:2829 a natural alternative 2809:2829 a natural alternative 2809:2829 Thus, these EOs rich in antimicrobial and antioxidant components can serve as a natural alternative; this confirms their use as additives in cosmetics. 37107083 12 35 contain have 2094:2097 arg2 capacity 2106:2113 a high capacity 2099:2113 a high capacity for scavenging free radicals from DPPH 2099:2152 The study of the antioxidant activity showed that all the EOs tested have a high capacity for scavenging free radicals from DPPH. 37107083 12 35 contain have 2094:2097 arg1 EOs 2083:2085 all the EOs 2075:2085 all the EOs tested 2075:2092 The study of the antioxidant activity showed that all the EOs tested have a high capacity for scavenging free radicals from DPPH. 37107083 5 36 theme composition 893:903 arg1 composition 893:903 the total composition 883:903 the total composition of EOs 883:910 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 5 36 theme composition 893:903 arg1 % 869:869 99.97% 864:869 99.97% 864:869 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 5 36 theme composition 893:903 arg1 % 878:878 100% 875:878 100% 875:878 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 2 37 theme sugars 498:503 arg1 presence 430:437 the presence 426:437 the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages 426:599 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 11 38 theme Chamaemelum 1686:1696 arg1 nobile 1698:1703 Chamaemelum nobile 1686:1703 Chamaemelum nobile 1686:1703 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 8 39 theme aurantium 1210:1218 arg1 rich 1223:1226 rich 1223:1226 rich 1223:1226 The EO of Citrus aurantium is rich in linalool (29.01%). 37107083 8 39 theme aurantium 1210:1218 arg1 EO 1197:1198 The EO 1193:1198 The EO of Citrus aurantium 1193:1218 The EO of Citrus aurantium is rich in linalool (29.01%). 37107083 5 40 theme EOs 908:910 arg1 composition 893:903 the total composition 883:903 the total composition of EOs 883:910 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 2 41 theme primary 442:448 arg1 metabolites 450:460 primary metabolites 442:460 primary metabolites 442:460 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 1 42 dep composition 147:157 arg1 the 134:136 the 134:136 the 134:136 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 5 43 theme composition 767:777 arg1 analysis 742:749 The analysis 738:749 The analysis of the chemical composition carried out by GC-MS 738:798 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 14 44 theme Antimicrobial 2374:2386 arg1 EO 2397:2398 Antimicrobial activity EO 2374:2398 Antimicrobial activity EO 2374:2398 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 5 45 dep 35 829:830 arg1 to 826:827 to 826:827 to 826:827 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 0 46 theme Biological 19:28 arg1 Activities 30:39 Biological Activities 19:39 Biological Activities 19:39 Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties. 37107083 1 47 dep Cedrus 321:326 arg1 atlantica 328:336 Cedrus atlantica 321:336 Cedrus atlantica 321:336 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 9 48 theme Pistacia 1260:1267 arg1 lentiscus 1269:1277 Pistacia lentiscus 1260:1277 Pistacia lentiscus 1260:1277 The EO of Pistacia lentiscus is dominated by 3-methylpentylangelate (27.83%). 37107083 14 49 theme strains 2630:2636 arg1 MICs 2608:2611 the MICs 2604:2611 the MICs of the bacterial strains 2604:2636 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 12 50 theme scavenging 2119:2128 arg1 radicals 2135:2142 scavenging free radicals 2119:2142 scavenging free radicals from DPPH 2119:2152 The study of the antioxidant activity showed that all the EOs tested have a high capacity for scavenging free radicals from DPPH. 37107083 10 51 theme Cedrus 1349:1354 arg1 atlantica 1356:1364 Cedrus atlantica 1349:1364 Cedrus atlantica 1349:1364 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 14 52 theme strains 2687:2693 arg1 MICs 2668:2671 the MICs 2664:2671 the MICs of the fungal strains 2664:2693 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 0 53 theme Oils 54:57 arg1 Phytochemistry 0:13 Phytochemistry 0:13 Phytochemistry 0:13 Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties. 37107083 0 53 theme Oils 54:57 arg1 Activities 30:39 Biological Activities 19:39 Biological Activities 19:39 Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties. 37107083 15 54 from antimicrobial 2755:2767 arg1 rich 2747:2750 rich 2747:2750 rich 2747:2750 Thus, these EOs rich in antimicrobial and antioxidant components can serve as a natural alternative; this confirms their use as additives in cosmetics. 37107083 15 55 from antioxidant 2773:2783 arg1 rich 2747:2750 rich 2747:2750 rich 2747:2750 Thus, these EOs rich in antimicrobial and antioxidant components can serve as a natural alternative; this confirms their use as additives in cosmetics. 37107083 13 56 theme aurantium 2351:2359 arg1 EO 2361:2362 then Citrus aurantium EO 2339:2362 then Citrus aurantium EO (14.70%) 2339:2371 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 13 56 theme aurantium 2351:2359 arg1 % 2370:2370 14.70% 2365:2370 14.70% 2365:2370 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 1 57 theme chemical 138:145 arg1 composition 147:157 chemical composition 138:157 chemical composition 138:157 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 15 58 from rich 2747:2750 arg1 antimicrobial 2755:2767 antimicrobial 2755:2767 antimicrobial 2755:2767 Thus, these EOs rich in antimicrobial and antioxidant components can serve as a natural alternative; this confirms their use as additives in cosmetics. 37107083 15 58 from rich 2747:2750 arg1 antioxidant 2773:2783 antioxidant 2773:2783 antioxidant 2773:2783 Thus, these EOs rich in antimicrobial and antioxidant components can serve as a natural alternative; this confirms their use as additives in cosmetics. 37107083 11 59 from monoterpenes 1739:1750 arg1 rich 1720:1723 rich 1720:1723 rich 1720:1723 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 11 60 theme third 1851:1855 arg1 gathers 1857:1863 the third gathers 1847:1863 the third gathers Pistacia lentiscus 1847:1882 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 7 61 theme nobile 1126:1131 arg1 EO 1133:1134 Chamaemelum nobile EO 1114:1134 Chamaemelum nobile EO 1114:1134 In Chamaemelum nobile EO, the most abundant compound is angelylangelate (41.79%). 37107083 1 62 theme nobilis 254:260 arg1 Pistacia 301:308 Pistacia 301:308 Pistacia 301:308 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 62 theme nobilis 254:260 arg1 EOs 227:229 EOs 227:229 EOs 227:229 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 62 theme nobilis 254:260 arg1 Rosa 343:346 Rosa 343:346 Rosa 343:346 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 62 theme nobilis 254:260 arg1 nobile 275:280 nobile 275:280 nobile 275:280 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 62 theme nobilis 254:260 arg1 Cedrus 321:326 Cedrus 321:326 Cedrus 321:326 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 62 theme nobilis 254:260 arg1 oils 221:224 the essential oils 207:224 the essential oils (EOs) of six species-Laurus nobilis 207:260 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 62 theme nobilis 254:260 arg1 aurantium 290:298 Citrus aurantium 283:298 Citrus aurantium 283:298 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 7 63 from angelylangelate 1167:1181 arg1 EO 1133:1134 Chamaemelum nobile EO 1114:1134 Chamaemelum nobile EO 1114:1134 In Chamaemelum nobile EO, the most abundant compound is angelylangelate (41.79%). 37107083 13 64 theme highest 2215:2221 arg1 activity 2223:2230 the highest activity 2211:2230 the highest activity 2211:2230 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 13 64 theme highest 2215:2221 arg1 % 2238:2238 76.84% 2233:2238 76.84% 2233:2238 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 13 64 theme highest 2215:2221 arg1 % 2249:2249 71.53% 2244:2249 71.53% 2244:2249 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 5 65 from variation 920:928 arg1 composition 946:956 the chemical composition 933:956 the chemical composition detected at the level of the majority compounds between these species 933:1026 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 1 66 theme antioxidant 163:173 arg1 activities 193:202 antioxidant and antimicrobial activities 163:202 activities 193:202 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 67 theme antimicrobial 179:191 arg1 activities 193:202 antioxidant and antimicrobial activities 163:202 activities 193:202 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 11 68 theme chemical 1567:1574 arg1 composition 1576:1586 the chemical composition 1563:1586 the chemical composition of the EOs 1563:1597 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 0 69 from Plants 87:92 arg1 Phytochemistry 0:13 Phytochemistry 0:13 Phytochemistry 0:13 Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties. 37107083 0 69 from Plants 87:92 arg1 Activities 30:39 Biological Activities 19:39 Biological Activities 19:39 Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties. 37107083 15 70 dep antimicrobial 2755:2767 arg1 components 2785:2794 components 2785:2794 components 2785:2794 Thus, these EOs rich in antimicrobial and antioxidant components can serve as a natural alternative; this confirms their use as additives in cosmetics. 37107083 1 71 theme essential 211:219 arg1 Pistacia 301:308 Pistacia 301:308 Pistacia 301:308 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 71 theme essential 211:219 arg1 EOs 227:229 EOs 227:229 EOs 227:229 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 71 theme essential 211:219 arg1 Rosa 343:346 Rosa 343:346 Rosa 343:346 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 71 theme essential 211:219 arg1 nobile 275:280 nobile 275:280 nobile 275:280 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 71 theme essential 211:219 arg1 Cedrus 321:326 Cedrus 321:326 Cedrus 321:326 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 71 theme essential 211:219 arg1 oils 221:224 the essential oils 207:224 the essential oils (EOs) of six species-Laurus nobilis 207:260 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 71 theme essential 211:219 arg1 aurantium 290:298 Citrus aurantium 283:298 Citrus aurantium 283:298 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 15 72 from additives 2859:2867 arg1 cosmetics 2872:2880 cosmetics 2872:2880 cosmetics 2872:2880 Thus, these EOs rich in antimicrobial and antioxidant components can serve as a natural alternative; this confirms their use as additives in cosmetics. 37107083 2 73 theme polysaccharides 510:524 arg1 presence 430:437 the presence 426:437 the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages 426:599 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 10 74 theme damascenaa 1414:1423 arg1 flowers 1425:1431 Rosa damascenaa flowers 1409:1431 Rosa damascenaa flowers 1409:1431 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 11 75 theme EOs 1595:1597 arg1 composition 1576:1586 the chemical composition 1563:1586 the chemical composition of the EOs 1563:1597 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 14 76 theme fungicidal 2534:2543 arg1 activities 2545:2554 significant bactericidal and fungicidal activities 2505:2554 significant bactericidal and fungicidal activities 2505:2554 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 5 77 theme compounds 996:1004 arg1 level 974:978 the level 970:978 the level of the majority compounds between these species 970:1026 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 6 78 theme major 1094:1098 arg1 component 1100:1108 the major component 1090:1108 the major component 1090:1108 Indeed, in the EO of Laurus nobilis, 1,8-cineole (36.58%) is the major component. 37107083 6 78 theme major 1094:1098 arg1 1,8-cineole 1066:1076 1,8-cineole 1066:1076 1,8-cineole (36.58%) 1066:1085 Indeed, in the EO of Laurus nobilis, 1,8-cineole (36.58%) is the major component. 37107083 6 79 from component 1100:1108 arg1 EO 1044:1045 the EO 1040:1045 the EO of Laurus nobilis 1040:1063 Indeed, in the EO of Laurus nobilis, 1,8-cineole (36.58%) is the major component. 37107083 13 80 theme nobilis 2173:2179 arg1 EOs 2159:2161 The EOs 2155:2161 The EOs of Laurus nobilis and Pistacia lentiscus 2155:2202 The EOs of Laurus nobilis and Pistacia lentiscus showed the highest activity, 76.84% and 71.53%, respectively, followed by Cedrus atlantica EO (62.38%) and Chamaemelum nobile (47.98%) then Citrus aurantium EO (14.70%). 37107083 2 81 theme secondary 536:544 arg1 flavonoids 575:584 flavonoids 575:584 flavonoids 575:584 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 2 81 theme secondary 536:544 arg1 metabolites 546:556 secondary metabolites 536:556 secondary metabolites such as tannins, flavonoids, and mucilages 536:599 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 2 81 theme secondary 536:544 arg1 tannins 566:572 tannins 566:572 tannins 566:572 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 2 81 theme secondary 536:544 arg1 mucilages 591:599 mucilages 591:599 mucilages 591:599 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 12 82 theme antioxidant 2042:2052 arg1 activity 2054:2061 the antioxidant activity 2038:2061 the antioxidant activity 2038:2061 The study of the antioxidant activity showed that all the EOs tested have a high capacity for scavenging free radicals from DPPH. 37107083 11 83 from rich 1819:1822 arg1 aurantium 1911:1919 Citrus aurantium 1904:1919 Citrus aurantium 1904:1919 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 11 83 from rich 1819:1822 arg1 nobilis 1892:1898 Laurus nobilis 1885:1898 Laurus nobilis 1885:1898 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 11 83 from rich 1819:1822 arg1 gathers 1857:1863 the third gathers 1847:1863 the third gathers Pistacia lentiscus 1847:1882 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 11 83 from rich 1819:1822 arg1 sesquiterpenes 1827:1840 sesquiterpenes 1827:1840 sesquiterpenes 1827:1840 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 0 84 theme Aromatic 68:75 arg1 Plants 87:92 Six Aromatic Medicinal Plants 64:92 Six Aromatic Medicinal Plants with Cosmetic Properties 64:117 Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties. 37107083 2 85 theme proteins 479:486 arg1 presence 430:437 the presence 426:437 the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages 426:599 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 11 86 from sesquiterpenes 1827:1840 arg1 rich 1819:1822 rich 1819:1822 rich 1819:1822 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 14 87 theme fungal 2680:2685 arg1 strains 2687:2693 the fungal strains 2676:2693 the fungal strains 2676:2693 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 2 88 theme lipids 471:476 arg1 presence 430:437 the presence 426:437 the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages 426:599 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 0 89 theme Cosmetic 99:106 arg1 Properties 108:117 Cosmetic Properties 99:117 Cosmetic Properties 99:117 Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties. 37107083 5 90 theme total 887:891 arg1 composition 893:903 the total composition 883:903 the total composition of EOs 883:910 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 1 91 dep Pistacia 301:308 arg1 lentiscus 310:318 Pistacia lentiscus 301:318 Pistacia lentiscus 301:318 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 11 92 dep rich 1720:1723 arg1 second 1757:1762 second 1757:1762 second 1757:1762 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 11 92 dep rich 1720:1723 arg1 defined 1764:1770 defined 1764:1770 defined 1764:1770 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 2 93 theme reducing 489:496 arg1 sugars 498:503 reducing sugars 489:503 reducing sugars 489:503 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 8 94 theme Citrus 1203:1208 arg1 aurantium 1210:1218 Citrus aurantium 1203:1218 Citrus aurantium 1203:1218 The EO of Citrus aurantium is rich in linalool (29.01%). 37107083 2 95 theme Phytochemical 377:389 arg1 screening 391:399 Phytochemical screening 377:399 Phytochemical screening of these plants 377:415 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 5 96 theme chemical 758:765 arg1 composition 767:777 the chemical composition 754:777 the chemical composition carried out by GC-MS 754:798 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 14 97 theme activity 2388:2395 arg1 EO 2397:2398 Antimicrobial activity EO 2374:2398 Antimicrobial activity EO 2374:2398 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 11 98 theme Citrus 1904:1909 arg1 aurantium 1911:1919 Citrus aurantium 1904:1919 Citrus aurantium 1904:1919 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 11 98 theme Citrus 1904:1909 arg1 sesquiterpenes 1827:1840 sesquiterpenes 1827:1840 sesquiterpenes 1827:1840 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 2 99 theme plants 410:415 arg1 screening 391:399 Phytochemical screening 377:399 Phytochemical screening of these plants 377:415 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 0 100 theme Essential 44:52 arg1 Oils 54:57 Essential Oils 44:57 Essential Oils 44:57 Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties. 37107083 1 101 theme Citrus 283:288 arg1 aurantium 290:298 Citrus aurantium 283:298 Citrus aurantium 283:298 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 1 101 theme Citrus 283:288 arg1 oils 221:224 the essential oils 207:224 the essential oils (EOs) of six species-Laurus nobilis 207:260 In this work, the chemical composition and antioxidant and antimicrobial activities of the essential oils (EOs) of six species-Laurus nobilis, Chamaemelum nobile, Citrus aurantium, Pistacia lentiscus, Cedrus atlantica, and Rosa damascena-have been studied. 37107083 12 102 theme free 2130:2133 arg1 radicals 2135:2142 scavenging free radicals 2119:2142 scavenging free radicals from DPPH 2119:2152 The study of the antioxidant activity showed that all the EOs tested have a high capacity for scavenging free radicals from DPPH. 37107083 11 103 dep sesquiterpenes 1955:1968 arg1 close 2017:2021 close 2017:2021 close 2017:2021 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 3 104 theme essential 606:614 arg1 oils 616:619 The essential oils 602:619 The essential oils 602:619 The essential oils were extracted by hydrodistillation in a Clevenger-type apparatus. 37107083 14 105 theme bacterial 2620:2628 arg1 strains 2630:2636 the bacterial strains 2616:2636 the bacterial strains 2616:2636 Antimicrobial activity EO was tested against eight bacterial strains and eight fungal strains; the results showed that EOs exhibit significant bactericidal and fungicidal activities against all the microorganisms tested, of which the MICs of the bacterial strains start with 5 mg/mL, while the MICs of the fungal strains are between 0.60 mg/mL and 5 mg/mL. 37107083 15 106 theme natural 2811:2817 arg1 EOs 2743:2745 these EOs 2737:2745 these EOs rich in antimicrobial and antioxidant components 2737:2794 Thus, these EOs rich in antimicrobial and antioxidant components can serve as a natural alternative; this confirms their use as additives in cosmetics. 37107083 15 106 theme natural 2811:2817 arg1 alternative 2819:2829 a natural alternative 2809:2829 a natural alternative 2809:2829 Thus, these EOs rich in antimicrobial and antioxidant components can serve as a natural alternative; this confirms their use as additives in cosmetics. 37107083 5 107 theme chemical 937:944 arg1 composition 946:956 the chemical composition 933:956 the chemical composition detected at the level of the majority compounds between these species 933:1026 The analysis of the chemical composition carried out by GC-MS showed the presence of 30 to 35 compounds and represent between 99.97% and 100% of the total composition of EOs, with a variation in the chemical composition detected at the level of the majority compounds between these species. 37107083 10 108 from rich 1436:1439 arg1 n-nonadecane 1444:1455 n-nonadecane 1444:1455 n-nonadecane (44.89%) 1444:1464 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 10 108 from rich 1436:1439 arg1 % 1463:1463 44.89% 1458:1463 44.89% 1458:1463 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 7 109 theme abundant 1146:1153 arg1 angelylangelate 1167:1181 angelylangelate 1167:1181 angelylangelate (41.79%) 1167:1190 In Chamaemelum nobile EO, the most abundant compound is angelylangelate (41.79%). 37107083 7 109 theme abundant 1146:1153 arg1 compound 1155:1162 the most abundant compound 1137:1162 the most abundant compound 1137:1162 In Chamaemelum nobile EO, the most abundant compound is angelylangelate (41.79%). 37107083 2 110 theme metabolites 450:460 arg1 presence 430:437 the presence 426:437 the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages 426:599 Phytochemical screening of these plants revealed the presence of primary metabolites, namely, lipids, proteins, reducing sugars, and polysaccharides, and also secondary metabolites such as tannins, flavonoids, and mucilages. 37107083 10 111 from n-nonadecane 1444:1455 arg1 EO 1403:1404 the EO 1399:1404 the EO of Rosa damascenaa flowers 1399:1431 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 10 111 from n-nonadecane 1444:1455 arg1 rich 1436:1439 rich 1436:1439 rich 1436:1439 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 12 112 theme high 2101:2104 arg1 capacity 2106:2113 a high capacity 2099:2113 a high capacity for scavenging free radicals from DPPH 2099:2152 The study of the antioxidant activity showed that all the EOs tested have a high capacity for scavenging free radicals from DPPH. 37107083 10 113 theme main 1332:1335 arg1 β-himachalene 1369:1381 β-himachalene 1369:1381 β-himachalene 1369:1381 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 10 113 theme main 1332:1335 arg1 compound 1337:1344 The main compound 1328:1344 The main compound of Cedrus atlantica 1328:1364 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 10 113 theme main 1332:1335 arg1 % 1389:1389 40.19% 1384:1389 40.19% 1384:1389 The main compound of Cedrus atlantica is β-himachalene (40.19%), while the EO of Rosa damascenaa flowers is rich in n-nonadecane (44.89%). 37107083 11 114 theme similarity 1487:1496 arg1 analysis 1471:1478 The analysis 1467:1478 The analysis of the similarity between the EOs of the plants studied by ACH and ACP 1467:1549 The analysis of the similarity between the EOs of the plants studied by ACH and ACP showed that the chemical composition of the EOs makes it possible to separate these plants into three groups: the first represented by Chamaemelum nobile, because it is rich in oxygenated monoterpenes, the second defined Cedrus atlantica and Rosa damascena, which are rich in sesquiterpenes, and the third gathers Pistacia lentiscus, Laurus nobilis and Citrus aurantium, which are composed of oxygenated sesquiterpenes and monoterpenes (these three species are very close). 37107083 8 115 from linalool 1231:1238 arg1 rich 1223:1226 rich 1223:1226 rich 1223:1226 The EO of Citrus aurantium is rich in linalool (29.01%). 37107083 8 115 from linalool 1231:1238 arg1 EO 1197:1198 The EO 1193:1198 The EO of Citrus aurantium 1193:1218 The EO of Citrus aurantium is rich in linalool (29.01%). 36213120 8 0 theme marker 1093:1098 arg1 concentrations 1100:1113 the SF-inflammatory marker concentrations 1073:1113 the SF-inflammatory marker concentrations 1073:1113 Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. 36213120 10 1 contain had 1605:1607 arg2 effect 1631:1636 no measurable effect 1617:1636 no measurable effect 1617:1636 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 10 1 contain had 1605:1607 arg1 lubricin 1551:1558 lubricin 1551:1558 lubricin with sialylated and nonsialylated T antigens 1551:1603 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 10 1 contain had 1605:1607 arg2 less 1609:1612 less 1609:1612 less 1609:1612 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 9 2 from level 1189:1193 arg1 patients 1239:1246 OA patients 1236:1246 OA patients 1236:1246 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 8 3 gly glycosylation 1141:1153 arg1 SF-lubricin 1158:1168 SF-lubricin 1158:1168 SF-lubricin 1158:1168 Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. 36213120 3 4 theme Inflammatory 500:511 arg1 markers 513:519 Inflammatory markers 500:519 Inflammatory markers in plasma and SF in OA patients and controls 500:564 Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. 36213120 6 5 theme plasma 846:851 arg1 MCP-4 853:857 Only plasma MCP-4 841:857 Only plasma MCP-4 841:857 Only plasma MCP-4 and TARC increased in our patient cohort compared to control plasma. 36213120 7 6 gly glycosylation 1037:1049 arg1 connection 1018:1027 a direct connection 1009:1027 a direct connection with SF glycosylation 1009:1049 To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. 36213120 8 7 theme altered 1133:1139 arg1 glycosylation 1141:1153 altered glycosylation 1133:1153 altered glycosylation of SF-lubricin 1133:1168 Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. 36213120 8 8 theme SF-inflammatory 1077:1091 arg1 concentrations 1100:1113 the SF-inflammatory marker concentrations 1073:1113 the SF-inflammatory marker concentrations 1073:1113 Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. 36213120 11 9 theme cytokine 1743:1750 arg1 production 1752:1761 synovial proinflammatory cytokine production 1718:1761 synovial proinflammatory cytokine production 1718:1761 These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation. 36213120 7 10 theme direct 1011:1016 arg1 connection 1018:1027 a direct connection 1009:1027 a direct connection with SF glycosylation 1009:1049 To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. 36213120 5 11 from difference 683:692 arg1 concentration 703:715 their concentration 697:715 their concentration 697:715 The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. 36213120 5 12 theme independent 782:792 arg1 environment 807:817 an independent inflammatory environment 779:817 an independent inflammatory environment in the two biofluids 779:838 The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. 36213120 10 13 theme T 1594:1594 arg1 antigens 1596:1603 sialylated and nonsialylated T antigens 1565:1603 sialylated and nonsialylated T antigens 1565:1603 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 9 14 from SF-VEGFA 1224:1231 arg1 patients 1239:1246 OA patients 1236:1246 OA patients 1236:1246 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 2 15 link O-linked 438:445 arg1 glycan 477:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan 438:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 438:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 11 16 theme local 1778:1782 arg1 inflammation 1793:1804 local synovial inflammation 1778:1804 local synovial inflammation 1778:1804 These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation. 36213120 9 17 theme SF-IL-8 1198:1204 arg1 level 1189:1193 the level 1185:1193 the level of SF-IL-8 1185:1204 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 9 17 theme SF-IL-8 1198:1204 arg1 SF-VEGFA 1224:1231 SF-VEGFA 1224:1231 SF-VEGFA 1224:1231 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 9 17 theme SF-IL-8 1198:1204 arg1 SF-MIP-1α 1210:1218 SF-MIP-1α 1210:1218 SF-MIP-1α 1210:1218 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 9 18 theme lubricin 1298:1305 arg1 glycosylation 1307:1319 the altered lubricin glycosylation 1286:1319 the altered lubricin glycosylation 1286:1319 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 9 19 with correlation 1269:1279 arg1 glycosylation 1307:1319 the altered lubricin glycosylation 1286:1319 the altered lubricin glycosylation 1286:1319 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 7 20 theme plasma 974:979 arg1 markers 981:987 plasma markers 974:987 plasma markers 974:987 To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. 36213120 2 21 from glycan 477:482 arg1 lubricin 490:497 SF lubricin 487:497 SF lubricin 487:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 1 22 theme local 307:311 arg1 inflammation 334:345 osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation 257:345 osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation 257:345 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 2 23 theme Tn 447:448 arg1 antigen 450:456 Tn antigen 447:456 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 438:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 2 23 theme Tn 447:448 arg1 GalNAcα1-Ser/Thr 459:474 GalNAcα1-Ser/Thr 459:474 GalNAcα1-Ser/Thr 459:474 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 0 24 from glycans 19:25 arg1 osteoarthritis 30:43 osteoarthritis 30:43 osteoarthritis 30:43 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 0 25 theme inflammatory 154:165 arg1 cytokines 167:175 inflammatory cytokines 154:175 inflammatory cytokines 154:175 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 11 26 theme synovial 1718:1725 arg1 production 1752:1761 synovial proinflammatory cytokine production 1718:1761 synovial proinflammatory cytokine production 1718:1761 These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation. 36213120 0 27 theme VEGFA 84:88 arg1 secretion 71:79 the synoviocyte secretion 55:79 the synoviocyte secretion of VEGFA, IL-8, and MIP-1α 55:106 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 1 28 theme synovial 314:321 arg1 SF 330:331 SF 330:331 SF 330:331 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 1 28 theme synovial 314:321 arg1 fluid 323:327 synovial fluid 314:327 synovial fluid 314:327 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 0 29 theme IL-8 91:94 arg1 secretion 71:79 the synoviocyte secretion 55:79 the synoviocyte secretion of VEGFA, IL-8, and MIP-1α 55:106 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 0 30 link O-linked 127:134 arg1 glycosylation 136:148 O-linked glycosylation 127:148 O-linked glycosylation 127:148 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 10 31 gly nonsialylated 1580:1592 arg1 antigens 1596:1603 sialylated and nonsialylated T antigens 1565:1603 sialylated and nonsialylated T antigens 1565:1603 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 9 32 theme positive 1260:1267 arg1 correlation 1269:1279 a positive correlation 1258:1279 a positive correlation with the altered lubricin glycosylation 1258:1319 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 2 33 from amount 428:433 arg1 lubricin 490:497 SF lubricin 487:497 SF lubricin 487:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 10 34 theme recombinant 1433:1443 arg1 lubricin 1445:1452 recombinant lubricin 1433:1452 recombinant lubricin 1433:1452 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 10 35 gly sialylated 1565:1574 arg1 antigens 1596:1603 sialylated and nonsialylated T antigens 1565:1603 sialylated and nonsialylated T antigens 1565:1603 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 0 36 theme Truncated 0:8 arg1 glycans 19:25 Truncated lubricin glycans 0:25 Truncated lubricin glycans in osteoarthritis 0:43 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 10 37 theme IL-8 1472:1475 arg1 secretion 1459:1467 the secretion 1455:1467 the secretion of IL-8 and MIP-1α and VEGFA 1455:1496 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 2 38 theme inflammatory 373:384 arg1 markers 386:392 inflammatory markers 373:392 inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 373:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 1 39 theme -related 276:283 arg1 inflammation 334:345 osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation 257:345 osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation 257:345 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 11 40 theme truncated 1663:1671 arg1 glycans 1673:1679 truncated glycans 1663:1679 truncated glycans of lubricin 1663:1691 These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation. 36213120 10 41 with lubricin 1551:1558 arg1 antigens 1596:1603 sialylated and nonsialylated T antigens 1565:1603 sialylated and nonsialylated T antigens 1565:1603 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 2 42 theme increased 418:426 arg1 glycan 477:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan 438:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 438:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 2 42 theme increased 418:426 arg1 amount 428:433 the increased amount 414:433 the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 414:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 10 43 theme VEGFA 1492:1496 arg1 secretion 1459:1467 the secretion 1455:1467 the secretion of IL-8 and MIP-1α and VEGFA 1455:1496 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 10 44 theme MIP-1α 1481:1486 arg1 secretion 1459:1467 the secretion 1455:1467 the secretion of IL-8 and MIP-1α and VEGFA 1455:1496 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 1 45 theme inflammatory 223:234 arg1 markers 236:242 inflammatory markers 223:242 inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation 223:345 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 1 46 theme relevant 244:251 arg1 markers 236:242 inflammatory markers 223:242 inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation 223:345 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 1 47 dep systemic 285:292 arg1 plasma 295:300 plasma 295:300 plasma 295:300 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 10 48 from controls 1388:1395 arg1 synoviocytes 1365:1376 fibroblast-like synoviocytes 1349:1376 fibroblast-like synoviocytes from both controls and OA patients 1349:1411 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 10 49 theme fibroblast-like 1349:1363 arg1 synoviocytes 1365:1376 fibroblast-like synoviocytes 1349:1376 fibroblast-like synoviocytes from both controls and OA patients 1349:1411 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 10 50 with lubricin 1518:1525 arg1 antigens 1535:1542 Tn antigens 1532:1542 Tn antigens 1532:1542 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 10 51 theme Tn 1532:1533 arg1 antigens 1535:1542 Tn antigens 1532:1542 Tn antigens 1532:1542 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 7 52 theme SF 1034:1035 arg1 glycosylation 1037:1049 SF glycosylation 1034:1049 SF glycosylation 1034:1049 To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. 36213120 6 53 theme Only 841:844 arg1 MCP-4 853:857 Only plasma MCP-4 841:857 Only plasma MCP-4 841:857 Only plasma MCP-4 and TARC increased in our patient cohort compared to control plasma. 36213120 10 54 theme sialylated 1565:1574 arg1 antigens 1596:1603 sialylated and nonsialylated T antigens 1565:1603 sialylated and nonsialylated T antigens 1565:1603 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 1 55 theme primary 182:188 arg1 aim 190:192 The primary aim 178:192 The primary aim of the study 178:205 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 9 56 theme OA 1236:1237 arg1 patients 1239:1246 OA patients 1236:1246 OA patients 1236:1246 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 10 57 from patients 1404:1411 arg1 synoviocytes 1365:1376 fibroblast-like synoviocytes 1349:1376 fibroblast-like synoviocytes from both controls and OA patients 1349:1411 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 8 58 theme glycosylation 1141:1153 arg1 level 1124:1128 the level 1120:1128 the level of altered glycosylation of SF-lubricin 1120:1168 Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. 36213120 6 59 theme control 912:918 arg1 plasma 920:925 control plasma 912:925 control plasma 912:925 Only plasma MCP-4 and TARC increased in our patient cohort compared to control plasma. 36213120 0 60 theme O-linked 127:134 arg1 glycosylation 136:148 O-linked glycosylation 127:148 O-linked glycosylation 127:148 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 3 61 theme OA 541:542 arg1 patients 544:551 OA patients 541:551 OA patients 541:551 Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. 36213120 5 62 theme inflammatory 794:805 arg1 environment 807:817 an independent inflammatory environment 779:817 an independent inflammatory environment in the two biofluids 779:838 The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. 36213120 8 63 theme SF-lubricin 1158:1168 arg1 glycosylation 1141:1153 altered glycosylation 1133:1153 altered glycosylation of SF-lubricin 1133:1168 Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. 36213120 2 64 theme SF 487:488 arg1 lubricin 490:497 SF lubricin 487:497 SF lubricin 487:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 10 65 theme nonsialylated 1580:1592 arg1 antigens 1596:1603 sialylated and nonsialylated T antigens 1565:1603 sialylated and nonsialylated T antigens 1565:1603 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 5 66 from environment 807:817 arg1 biofluids 830:838 the two biofluids 822:838 the two biofluids 822:838 The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. 36213120 6 67 theme patient 885:891 arg1 cohort 893:898 our patient cohort 881:898 our patient cohort 881:898 Only plasma MCP-4 and TARC increased in our patient cohort compared to control plasma. 36213120 3 68 from markers 513:519 arg1 SF 535:536 SF 535:536 SF 535:536 Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. 36213120 3 68 from markers 513:519 arg1 plasma 524:529 plasma 524:529 plasma 524:529 Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. 36213120 11 69 theme synovial 1784:1791 arg1 inflammation 1793:1804 local synovial inflammation 1778:1804 local synovial inflammation 1778:1804 These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation. 36213120 11 70 dep promote 1710:1716 arg1 found 1697:1701 found 1697:1701 found in OA 1697:1707 These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation. 36213120 3 71 from plasma 524:529 arg1 controls 557:564 controls 557:564 controls 557:564 Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. 36213120 3 71 from plasma 524:529 arg1 patients 544:551 OA patients 541:551 OA patients 541:551 Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. 36213120 7 72 theme second 943:948 arg1 task 950:953 the second task 939:953 the second task 939:953 To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. 36213120 2 73 theme antigen 450:456 arg1 glycan 477:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan 438:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 438:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 2 74 theme O-linked 438:445 arg1 glycan 477:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan 438:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 438:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 11 75 theme proinflammatory 1727:1741 arg1 production 1752:1761 synovial proinflammatory cytokine production 1718:1761 synovial proinflammatory cytokine production 1718:1761 These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation. 36213120 5 76 from correlation 729:739 arg1 concentration 703:715 their concentration 697:715 their concentration 697:715 The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. 36213120 2 77 theme glycan 477:482 arg1 glycan 477:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan 438:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 438:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 2 77 theme glycan 477:482 arg1 amount 428:433 the increased amount 414:433 the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 414:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 10 78 theme OA 1401:1402 arg1 patients 1404:1411 OA patients 1401:1411 OA patients 1401:1411 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 0 79 theme MIP-1α 101:106 arg1 secretion 71:79 the synoviocyte secretion 55:79 the synoviocyte secretion of VEGFA, IL-8, and MIP-1α 55:106 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 4 80 located detected 647:654 arg1 plasma 664:669 plasma 664:669 plasma 664:669 We found consistently 29 markers detected in both plasma and SF. 36213120 4 80 located detected 647:654 arg2 markers 639:645 29 markers 636:645 29 markers detected in both plasma and SF 636:676 We found consistently 29 markers detected in both plasma and SF. 36213120 4 80 located detected 647:654 arg1 SF 675:676 SF 675:676 SF 675:676 We found consistently 29 markers detected in both plasma and SF. 36213120 10 81 theme lubricin 1445:1452 arg1 glycovariants 1416:1428 glycovariants 1416:1428 glycovariants of recombinant lubricin 1416:1452 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 0 82 theme lubricin 10:17 arg1 glycans 19:25 Truncated lubricin glycans 0:25 Truncated lubricin glycans in osteoarthritis 0:43 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 9 83 gly glycosylation 1307:1319 arg1 correlation 1269:1279 a positive correlation 1258:1279 a positive correlation with the altered lubricin glycosylation 1258:1319 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 3 84 from SF 535:536 arg1 controls 557:564 controls 557:564 controls 557:564 Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. 36213120 3 84 from SF 535:536 arg1 patients 544:551 OA patients 541:551 OA patients 541:551 Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. 36213120 1 85 dep local 307:311 arg1 SF 330:331 SF 330:331 SF 330:331 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 1 85 dep local 307:311 arg1 fluid 323:327 synovial fluid 314:327 synovial fluid 314:327 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 3 86 theme 44-multiplex 588:599 arg1 immunoassay 601:611 a 44-multiplex immunoassay 586:611 a 44-multiplex immunoassay 586:611 Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. 36213120 5 87 theme low 725:727 arg1 correlation 729:739 the low correlation 721:739 the low correlation when comparing SF and plasma 721:768 The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. 36213120 1 88 theme systemic 285:292 arg1 inflammation 334:345 osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation 257:345 osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation 257:345 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 1 89 theme study 201:205 arg1 aim 190:192 The primary aim 178:192 The primary aim of the study 178:205 The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. 36213120 9 90 theme altered 1290:1296 arg1 glycosylation 1307:1319 the altered lubricin glycosylation 1286:1319 the altered lubricin glycosylation 1286:1319 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36213120 10 91 theme measurable 1620:1629 arg1 effect 1631:1636 no measurable effect 1617:1636 no measurable effect 1617:1636 Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. 36213120 0 92 theme synoviocyte 59:69 arg1 secretion 71:79 the synoviocyte secretion 55:79 the synoviocyte secretion of VEGFA, IL-8, and MIP-1α 55:106 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 0 93 dep stimulate 45:53 arg1 Interplay 109:117 Interplay 109:117 Interplay between O-linked glycosylation and inflammatory cytokines 109:175 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. 36213120 7 94 with connection 1018:1027 arg1 glycosylation 1037:1049 SF glycosylation 1034:1049 SF glycosylation 1034:1049 To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. 36213120 11 95 theme lubricin 1684:1691 arg1 glycans 1673:1679 truncated glycans 1663:1679 truncated glycans of lubricin 1663:1691 These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation. 36213120 2 96 from lubricin 490:497 arg1 glycan 477:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan 438:482 O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 438:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 2 96 from lubricin 490:497 arg1 amount 428:433 the increased amount 414:433 the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin 414:497 From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. 36213120 9 97 from SF-MIP-1α 1210:1218 arg1 patients 1239:1246 OA patients 1236:1246 OA patients 1236:1246 We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. 36760344 8 0 theme microbiota 1163:1172 arg1 function 1144:1151 the function 1140:1151 the function of faecal microbiota 1140:1172 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was used to predict the function of faecal microbiota. 36760344 12 1 theme beneficial 1466:1475 arg1 genera 1487:1492 two beneficial bacterial genera 1462:1492 two beneficial bacterial genera (Megamonas and Faecalibacterium) 1462:1525 According to the LEfSe analysis, two beneficial bacterial genera (Megamonas and Faecalibacterium) were significantly enriched in the meditation group. 36760344 13 2 dep biosynthesis-were 1713:1729 arg1 enriched 1745:1752 enriched 1745:1752 biosynthesis-were significantly enriched in the meditation group 1713:1776 Functional predictive analysis further showed that several pathways-including glycan biosynthesis, metabolism and lipopolysaccharide biosynthesis-were significantly enriched in the meditation group. 36760344 5 3 theme microbiome 669:678 arg1 structure 680:688 the gut microbiome structure 661:688 the gut microbiome structure 661:688 Aims To investigate the effects of long-term deep meditation on the gut microbiome structure. 36760344 6 4 theme Buddhist 803:810 arg1 monks 812:816 56 Tibetan Buddhist monks 792:816 56 Tibetan Buddhist monks 792:816 Methods To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. 36760344 7 5 theme sequencing 859:868 arg1 data 870:873 the sequencing data 855:873 the sequencing data 855:873 Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. 36760344 14 6 theme risk 1815:1818 arg1 meditation 1983:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 14 6 theme risk 1815:1818 arg1 factors 1820:1826 clinical risk factors 1806:1826 clinical risk factors 1806:1826 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 14 6 theme risk 1815:1818 arg1 cholesterol 1898:1908 total cholesterol 1892:1908 total cholesterol 1892:1908 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 12 7 theme LEfSe 1446:1450 arg1 analysis 1452:1459 the LEfSe analysis 1442:1459 the LEfSe analysis 1442:1459 According to the LEfSe analysis, two beneficial bacterial genera (Megamonas and Faecalibacterium) were significantly enriched in the meditation group. 36760344 5 8 theme long-term 632:640 arg1 meditation 647:656 long-term deep meditation 632:656 long-term deep meditation 632:656 Aims To investigate the effects of long-term deep meditation on the gut microbiome structure. 36760344 1 9 theme microbiota-gut-brain 182:201 arg1 axis 203:206 the microbiota-gut-brain axis 178:206 the microbiota-gut-brain axis 178:206 Background Advancements in research have confirmed that gut microbiota can influence health through the microbiota-gut-brain axis. 36760344 5 10 theme meditation 647:656 arg1 effects 621:627 the effects 617:627 the effects of long-term deep meditation on the gut microbiome structure 617:688 Aims To investigate the effects of long-term deep meditation on the gut microbiome structure. 36760344 8 11 theme Phylogenetic 1020:1031 arg1 Investigation 1033:1045 Phylogenetic Investigation 1020:1045 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis 1020:1118 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was used to predict the function of faecal microbiota. 36760344 16 12 theme immune 2278:2283 arg1 function 2285:2292 immune function 2278:2292 immune function 2278:2292 The microbiota enriched in monks was associated with a reduced risk of anxiety, depression and cardiovascular disease and could enhance immune function. 36760344 14 13 theme clinical 1806:1813 arg1 meditation 1983:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 14 13 theme clinical 1806:1813 arg1 factors 1820:1826 clinical risk factors 1806:1826 clinical risk factors 1806:1826 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 14 13 theme clinical 1806:1813 arg1 cholesterol 1898:1908 total cholesterol 1892:1908 total cholesterol 1892:1908 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 13 14 theme pathways-including 1639:1656 arg1 biosynthesis 1665:1676 several pathways-including glycan biosynthesis 1631:1676 several pathways-including glycan biosynthesis 1631:1676 Functional predictive analysis further showed that several pathways-including glycan biosynthesis, metabolism and lipopolysaccharide biosynthesis-were significantly enriched in the meditation group. 36760344 13 15 theme predictive 1591:1600 arg1 analysis 1602:1609 Functional predictive analysis 1580:1609 Functional predictive analysis 1580:1609 Functional predictive analysis further showed that several pathways-including glycan biosynthesis, metabolism and lipopolysaccharide biosynthesis-were significantly enriched in the meditation group. 36760344 2 16 theme inner 227:231 arg1 exercise 240:247 an inner mental exercise 224:247 an inner mental exercise 224:247 Meditation, as an inner mental exercise, can positively impact the regulation of an individual's physical and mental health. 36760344 10 17 theme α-diversity 1248:1258 arg1 indices 1260:1266 The α-diversity indices 1244:1266 Results The α-diversity indices of the meditation and control groups 1236:1303 Results The α-diversity indices of the meditation and control groups differed significantly. 36760344 14 18 theme Buddhist 1974:1981 arg1 meditation 1983:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 0 19 theme deep 61:64 arg1 meditation 66:75 long-term deep meditation 51:75 long-term deep meditation 51:75 Alteration of faecal microbiota balance related to long-term deep meditation. 36760344 5 20 from effects 621:627 arg1 structure 680:688 the gut microbiome structure 661:688 the gut microbiome structure 661:688 Aims To investigate the effects of long-term deep meditation on the gut microbiome structure. 36760344 17 21 theme psychosomatic 2367:2379 arg1 conditions 2381:2390 psychosomatic conditions 2367:2390 psychosomatic conditions 2367:2390 Overall, these results suggest that meditation plays a positive role in psychosomatic conditions and well-being. 36760344 16 22 theme anxiety 2213:2219 arg1 risk 2205:2208 a reduced risk 2195:2208 a reduced risk of anxiety, depression and cardiovascular disease 2195:2258 The microbiota enriched in monks was associated with a reduced risk of anxiety, depression and cardiovascular disease and could enhance immune function. 36760344 10 23 theme meditation 1275:1284 arg1 groups 1298:1303 the meditation and control groups 1271:1303 groups 1298:1303 Results The α-diversity indices of the meditation and control groups differed significantly. 36760344 7 24 theme intestinal 963:972 arg1 communities 984:994 differential intestinal microbial communities 950:994 differential intestinal microbial communities between the two groups 950:1017 Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. 36760344 4 25 theme microbiota 525:534 arg1 homeostasis 536:546 gut microbiota homeostasis 521:546 gut microbiota homeostasis 521:546 Therefore, we propose that long-term meditation may regulate gut microbiota homeostasis and, in turn, affect physical and mental health. 36760344 16 26 theme depression 2222:2231 arg1 risk 2205:2208 a reduced risk 2195:2208 a reduced risk of anxiety, depression and cardiovascular disease 2195:2258 The microbiota enriched in monks was associated with a reduced risk of anxiety, depression and cardiovascular disease and could enhance immune function. 36760344 9 27 theme biochemical 1201:1211 arg1 indices 1213:1219 biochemical indices 1201:1219 biochemical indices in the plasma 1201:1233 In addition, we evaluated biochemical indices in the plasma. 36760344 3 28 theme few 343:345 arg1 studies 347:353 few studies 343:353 few studies 343:353 However, few studies have comprehensively investigated faecal microbiota following long-term (several years) deep meditation. 36760344 3 29 dep long-term 417:425 arg1 years 436:440 several years 428:440 several years 428:440 However, few studies have comprehensively investigated faecal microbiota following long-term (several years) deep meditation. 36760344 6 30 theme intestinal 714:723 arg1 flora 725:729 the intestinal flora 710:729 the intestinal flora 710:729 Methods To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. 36760344 1 31 theme Background 78:87 arg1 Advancements 89:100 Background Advancements 78:100 Background Advancements in research 78:112 Background Advancements in research have confirmed that gut microbiota can influence health through the microbiota-gut-brain axis. 36760344 10 32 theme control 1290:1296 arg1 groups 1298:1303 the meditation and control groups 1271:1303 groups 1298:1303 Results The α-diversity indices of the meditation and control groups differed significantly. 36760344 8 33 theme States 1094:1099 arg1 analysis 1111:1118 Unobserved States (PICRUSt) analysis 1083:1118 Unobserved States (PICRUSt) analysis 1083:1118 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was used to predict the function of faecal microbiota. 36760344 17 34 theme positive 2350:2357 arg1 role 2359:2362 a positive role 2348:2362 a positive role 2348:2362 Overall, these results suggest that meditation plays a positive role in psychosomatic conditions and well-being. 36760344 0 35 theme faecal 14:19 arg1 balance 32:38 faecal microbiota balance 14:38 faecal microbiota balance 14:38 Alteration of faecal microbiota balance related to long-term deep meditation. 36760344 3 36 theme several 428:434 arg1 years 436:440 several years 428:440 several years 428:440 However, few studies have comprehensively investigated faecal microbiota following long-term (several years) deep meditation. 36760344 4 37 theme physical 569:576 arg1 health 589:594 physical and mental health 569:594 physical and mental health 569:594 Therefore, we propose that long-term meditation may regulate gut microbiota homeostasis and, in turn, affect physical and mental health. 36760344 0 38 theme balance 32:38 arg1 Alteration 0:9 Alteration 0:9 Alteration of faecal microbiota balance 0:38 Alteration of faecal microbiota balance related to long-term deep meditation. 36760344 14 39 theme total 1892:1896 arg1 cholesterol 1898:1908 total cholesterol 1892:1908 total cholesterol 1892:1908 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 8 40 theme analysis 1111:1118 arg1 Reconstruction 1065:1078 Reconstruction 1065:1078 Reconstruction of Unobserved States (PICRUSt) analysis 1065:1118 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was used to predict the function of faecal microbiota. 36760344 3 41 theme long-term 417:425 arg1 meditation 448:457 long-term (several years) deep meditation 417:457 long-term (several years) deep meditation 417:457 However, few studies have comprehensively investigated faecal microbiota following long-term (several years) deep meditation. 36760344 15 42 theme control 2124:2130 arg1 subjects 2132:2139 the monks and control subjects 2110:2139 subjects 2132:2139 We confirmed that the gut microbiota composition differed between the monks and control subjects. 36760344 14 43 dep Long-term 1944:1952 arg1 Conclusions 1932:1942 Conclusions 1932:1942 Conclusions 1932:1942 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 14 43 dep Long-term 1944:1952 arg1 B. 1929:1930 B. 1929:1930 B. 1929:1930 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 15 44 theme monks 2114:2118 arg1 subjects 2132:2139 the monks and control subjects 2110:2139 subjects 2132:2139 We confirmed that the gut microbiota composition differed between the monks and control subjects. 36760344 14 45 theme meditation 1864:1873 arg1 group 1875:1879 the meditation group 1860:1879 the meditation group 1860:1879 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 6 46 theme residents 835:843 arg1 samples 781:787 faecal samples 774:787 faecal samples of 56 Tibetan Buddhist monks and neighbouring residents 774:843 Methods To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. 36760344 14 47 theme traditional 1954:1964 arg1 meditation 1983:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 11 48 theme meditation 1411:1420 arg1 group 1422:1426 the meditation group 1407:1426 the meditation group 1407:1426 At the genus level, Prevotella and Bacteroides were significantly enriched in the meditation group. 36760344 6 49 theme rRNA 736:739 arg1 sequencing 746:755 16S rRNA gene sequencing 732:755 16S rRNA gene sequencing 732:755 Methods To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. 36760344 8 50 used used 1124:1127 arg2 Investigation 1033:1045 Phylogenetic Investigation 1020:1045 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis 1020:1118 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was used to predict the function of faecal microbiota. 36760344 12 51 theme bacterial 1477:1485 arg1 genera 1487:1492 two beneficial bacterial genera 1462:1492 two beneficial bacterial genera (Megamonas and Faecalibacterium) 1462:1525 According to the LEfSe analysis, two beneficial bacterial genera (Megamonas and Faecalibacterium) were significantly enriched in the meditation group. 36760344 8 52 theme faecal 1156:1161 arg1 microbiota 1163:1172 faecal microbiota 1156:1172 faecal microbiota 1156:1172 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was used to predict the function of faecal microbiota. 36760344 4 53 theme mental 582:587 arg1 health 589:594 physical and mental health 569:594 physical and mental health 569:594 Therefore, we propose that long-term meditation may regulate gut microbiota homeostasis and, in turn, affect physical and mental health. 36760344 5 54 theme gut 665:667 arg1 structure 680:688 the gut microbiome structure 661:688 the gut microbiome structure 661:688 Aims To investigate the effects of long-term deep meditation on the gut microbiome structure. 36760344 6 55 theme monks 812:816 arg1 samples 781:787 faecal samples 774:787 faecal samples of 56 Tibetan Buddhist monks and neighbouring residents 774:843 Methods To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. 36760344 13 56 theme glycan 1658:1663 arg1 biosynthesis 1665:1676 several pathways-including glycan biosynthesis 1631:1676 several pathways-including glycan biosynthesis 1631:1676 Functional predictive analysis further showed that several pathways-including glycan biosynthesis, metabolism and lipopolysaccharide biosynthesis-were significantly enriched in the meditation group. 36760344 7 57 theme linear 876:881 arg1 analysis 896:903 linear discriminant analysis effect size (LEfSe) 876:923 linear discriminant analysis effect size (LEfSe) 876:923 Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. 36760344 14 58 theme factors 1820:1826 arg1 levels 1796:1801 plasma levels 1789:1801 plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1789:1992 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 6 59 theme Tibetan 795:801 arg1 monks 812:816 56 Tibetan Buddhist monks 792:816 56 Tibetan Buddhist monks 792:816 Methods To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. 36760344 5 60 theme deep 642:645 arg1 meditation 647:656 long-term deep meditation 632:656 long-term deep meditation 632:656 Aims To investigate the effects of long-term deep meditation on the gut microbiome structure. 36760344 2 61 theme mental 319:324 arg1 health 326:331 an individual's physical and mental health 290:331 an individual's physical and mental health 290:331 Meditation, as an inner mental exercise, can positively impact the regulation of an individual's physical and mental health. 36760344 7 62 dep analysis 896:903 arg1 size 912:915 effect size 905:915 linear discriminant analysis effect size (LEfSe) 876:923 Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. 36760344 7 62 dep analysis 896:903 arg1 LEfSe 918:922 LEfSe 918:922 LEfSe 918:922 Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. 36760344 13 63 theme several 1631:1637 arg1 biosynthesis 1665:1676 several pathways-including glycan biosynthesis 1631:1676 several pathways-including glycan biosynthesis 1631:1676 Functional predictive analysis further showed that several pathways-including glycan biosynthesis, metabolism and lipopolysaccharide biosynthesis-were significantly enriched in the meditation group. 36760344 14 64 theme mental 2029:2034 arg1 health 2036:2041 physical and mental health 2016:2041 physical and mental health 2016:2041 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 13 65 theme Functional 1580:1589 arg1 analysis 1602:1609 Functional predictive analysis 1580:1609 Functional predictive analysis 1580:1609 Functional predictive analysis further showed that several pathways-including glycan biosynthesis, metabolism and lipopolysaccharide biosynthesis-were significantly enriched in the meditation group. 36760344 14 66 theme physical 2016:2023 arg1 health 2036:2041 physical and mental health 2016:2041 physical and mental health 2016:2041 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 12 67 dep genera 1487:1492 arg1 Faecalibacterium 1509:1524 Faecalibacterium 1509:1524 Faecalibacterium 1509:1524 According to the LEfSe analysis, two beneficial bacterial genera (Megamonas and Faecalibacterium) were significantly enriched in the meditation group. 36760344 12 67 dep genera 1487:1492 arg1 Megamonas 1495:1503 Megamonas 1495:1503 Megamonas 1495:1503 According to the LEfSe analysis, two beneficial bacterial genera (Megamonas and Faecalibacterium) were significantly enriched in the meditation group. 36760344 14 68 theme plasma 1789:1794 arg1 levels 1796:1801 plasma levels 1789:1801 plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1789:1992 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 2 69 theme mental 233:238 arg1 exercise 240:247 an inner mental exercise 224:247 an inner mental exercise 224:247 Meditation, as an inner mental exercise, can positively impact the regulation of an individual's physical and mental health. 36760344 16 70 theme cardiovascular 2237:2250 arg1 disease 2252:2258 cardiovascular disease 2237:2258 cardiovascular disease 2237:2258 The microbiota enriched in monks was associated with a reduced risk of anxiety, depression and cardiovascular disease and could enhance immune function. 36760344 6 71 theme faecal 774:779 arg1 samples 781:787 faecal samples 774:787 faecal samples of 56 Tibetan Buddhist monks and neighbouring residents 774:843 Methods To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. 36760344 1 72 theme gut 134:136 arg1 microbiota 138:147 gut microbiota 134:147 gut microbiota 134:147 Background Advancements in research have confirmed that gut microbiota can influence health through the microbiota-gut-brain axis. 36760344 2 73 theme physical 306:313 arg1 health 326:331 an individual's physical and mental health 290:331 an individual's physical and mental health 290:331 Meditation, as an inner mental exercise, can positively impact the regulation of an individual's physical and mental health. 36760344 14 74 theme Tibetan 1966:1972 arg1 meditation 1983:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 4 75 theme gut 521:523 arg1 homeostasis 536:546 gut microbiota homeostasis 521:546 gut microbiota homeostasis 521:546 Therefore, we propose that long-term meditation may regulate gut microbiota homeostasis and, in turn, affect physical and mental health. 36760344 9 76 from indices 1213:1219 arg1 plasma 1228:1233 the plasma 1224:1233 the plasma 1224:1233 In addition, we evaluated biochemical indices in the plasma. 36760344 8 77 theme Communities 1050:1060 arg1 Investigation 1033:1045 Phylogenetic Investigation 1020:1045 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis 1020:1118 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was used to predict the function of faecal microbiota. 36760344 14 78 theme Long-term 1944:1952 arg1 meditation 1983:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation 1914:1992 Moreover, plasma levels of clinical risk factors were significantly decreased in the meditation group, including total cholesterol and apolipoprotein B. Conclusions Long-term traditional Tibetan Buddhist meditation may positively impact physical and mental health. 36760344 12 79 theme meditation 1562:1571 arg1 group 1573:1577 the meditation group 1558:1577 the meditation group 1558:1577 According to the LEfSe analysis, two beneficial bacterial genera (Megamonas and Faecalibacterium) were significantly enriched in the meditation group. 36760344 7 80 theme microbial 974:982 arg1 communities 984:994 differential intestinal microbial communities 950:994 differential intestinal microbial communities between the two groups 950:1017 Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. 36760344 4 81 theme long-term 487:495 arg1 meditation 497:506 long-term meditation 487:506 long-term meditation 487:506 Therefore, we propose that long-term meditation may regulate gut microbiota homeostasis and, in turn, affect physical and mental health. 36760344 8 82 theme Unobserved 1083:1092 arg1 PICRUSt 1102:1108 PICRUSt 1102:1108 PICRUSt 1102:1108 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was used to predict the function of faecal microbiota. 36760344 8 82 theme Unobserved 1083:1092 arg1 States 1094:1099 Unobserved States 1083:1099 Unobserved States (PICRUSt) analysis 1083:1118 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was used to predict the function of faecal microbiota. 36760344 7 83 theme differential 950:961 arg1 communities 984:994 differential intestinal microbial communities 950:994 differential intestinal microbial communities between the two groups 950:1017 Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. 36760344 1 84 from Advancements 89:100 arg1 research 105:112 research 105:112 research 105:112 Background Advancements in research have confirmed that gut microbiota can influence health through the microbiota-gut-brain axis. 36760344 11 85 theme genus 1336:1340 arg1 level 1342:1346 the genus level 1332:1346 the genus level 1332:1346 At the genus level, Prevotella and Bacteroides were significantly enriched in the meditation group. 36760344 10 86 theme groups 1298:1303 arg1 indices 1260:1266 The α-diversity indices 1244:1266 Results The α-diversity indices of the meditation and control groups 1236:1303 Results The α-diversity indices of the meditation and control groups differed significantly. 36760344 10 87 dep Results 1236:1242 arg1 indices 1260:1266 The α-diversity indices 1244:1266 Results The α-diversity indices of the meditation and control groups 1236:1303 Results The α-diversity indices of the meditation and control groups differed significantly. 36760344 16 88 theme disease 2252:2258 arg1 risk 2205:2208 a reduced risk 2195:2208 a reduced risk of anxiety, depression and cardiovascular disease 2195:2258 The microbiota enriched in monks was associated with a reduced risk of anxiety, depression and cardiovascular disease and could enhance immune function. 36760344 15 89 theme gut 2066:2068 arg1 composition 2081:2091 the gut microbiota composition 2062:2091 the gut microbiota composition 2062:2091 We confirmed that the gut microbiota composition differed between the monks and control subjects. 36760344 3 90 theme deep 443:446 arg1 meditation 448:457 long-term (several years) deep meditation 417:457 long-term (several years) deep meditation 417:457 However, few studies have comprehensively investigated faecal microbiota following long-term (several years) deep meditation. 36760344 0 91 theme microbiota 21:30 arg1 balance 32:38 faecal microbiota balance 14:38 faecal microbiota balance 14:38 Alteration of faecal microbiota balance related to long-term deep meditation. 36760344 3 92 theme faecal 389:394 arg1 microbiota 396:405 faecal microbiota 389:405 faecal microbiota 389:405 However, few studies have comprehensively investigated faecal microbiota following long-term (several years) deep meditation. 36760344 13 93 theme meditation 1761:1770 arg1 group 1772:1776 the meditation group 1757:1776 the meditation group 1757:1776 Functional predictive analysis further showed that several pathways-including glycan biosynthesis, metabolism and lipopolysaccharide biosynthesis-were significantly enriched in the meditation group. 36760344 0 94 theme long-term 51:59 arg1 meditation 66:75 long-term deep meditation 51:75 long-term deep meditation 51:75 Alteration of faecal microbiota balance related to long-term deep meditation. 36760344 15 95 theme microbiota 2070:2079 arg1 composition 2081:2091 the gut microbiota composition 2062:2091 the gut microbiota composition 2062:2091 We confirmed that the gut microbiota composition differed between the monks and control subjects. 36760344 4 96 dep regulate 512:519 arg1 affect 562:567 affect 562:567 affect physical and mental health 562:594 Therefore, we propose that long-term meditation may regulate gut microbiota homeostasis and, in turn, affect physical and mental health. 36760344 16 97 theme reduced 2197:2203 arg1 risk 2205:2208 a reduced risk 2195:2208 a reduced risk of anxiety, depression and cardiovascular disease 2195:2258 The microbiota enriched in monks was associated with a reduced risk of anxiety, depression and cardiovascular disease and could enhance immune function. 36760344 6 98 theme gene 741:744 arg1 sequencing 746:755 16S rRNA gene sequencing 732:755 16S rRNA gene sequencing 732:755 Methods To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. 36760344 2 99 theme health 326:331 arg1 regulation 276:285 the regulation 272:285 the regulation of an individual's physical and mental health 272:331 Meditation, as an inner mental exercise, can positively impact the regulation of an individual's physical and mental health. 36760344 7 100 theme effect 905:910 arg1 size 912:915 effect size 905:915 linear discriminant analysis effect size (LEfSe) 876:923 Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. 36760344 7 100 theme effect 905:910 arg1 LEfSe 918:922 LEfSe 918:922 LEfSe 918:922 Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. 36760344 6 101 theme neighbouring 822:833 arg1 residents 835:843 neighbouring residents 822:843 neighbouring residents 822:843 Methods To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. 36760344 6 102 theme 16S 732:734 arg1 sequencing 746:755 16S rRNA gene sequencing 732:755 16S rRNA gene sequencing 732:755 Methods To examine the intestinal flora, 16S rRNA gene sequencing was performed on faecal samples of 56 Tibetan Buddhist monks and neighbouring residents. 36760344 7 103 theme discriminant 883:894 arg1 analysis 896:903 linear discriminant analysis effect size (LEfSe) 876:923 linear discriminant analysis effect size (LEfSe) 876:923 Based on the sequencing data, linear discriminant analysis effect size (LEfSe) was employed to identify differential intestinal microbial communities between the two groups. 35736250 3 0 from outbreaks 644:652 arg1 regions 679:685 previously infrequent regions 657:685 previously infrequent regions 657:685 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 3 0 from outbreaks 644:652 arg1 emergence 703:711 the greater emergence 691:711 the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus 691:811 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 4 1 theme real 951:954 arg1 reasons 956:962 the real reasons 947:962 the real reasons for the increased incidence of fungal infection 947:1010 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 4 1 theme real 951:954 arg1 what 938:941 what 938:941 what 938:941 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 3 2 theme pathogenic 721:730 arg1 variants 739:746 more pathogenic fungal variants 716:746 more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus 716:811 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 4 3 theme fungal 878:883 arg1 infections 885:894 prevalent severe fungal infections 861:894 prevalent severe fungal infections 861:894 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 1 4 theme common 142:147 arg1 infections 118:127 Fungal infections 111:127 Fungal infections 111:127 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 1 4 theme common 142:147 arg1 infections 159:168 the most common secondary infections 133:168 the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression 133:246 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 3 5 dep outbreaks 644:652 arg1 both 622:625 both 622:625 both 622:625 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 7 6 theme current 1327:1333 arg1 scenario 1335:1342 the current scenario 1323:1342 the current scenario of increasing severity of these infections 1323:1385 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 1 7 theme secondary 149:157 arg1 infections 118:127 Fungal infections 111:127 Fungal infections 111:127 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 1 7 theme secondary 149:157 arg1 infections 159:168 the most common secondary infections 133:168 the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression 133:246 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 3 8 theme infrequent 668:677 arg1 regions 679:685 previously infrequent regions 657:685 previously infrequent regions 657:685 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 7 9 from importance 1205:1214 arg1 adaptation 1278:1287 the adaptation 1274:1287 the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections 1274:1385 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 3 10 theme Cryptococcus 794:805 arg1 genus 807:811 the Cryptococcus genus 790:811 the Cryptococcus genus 790:811 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 4 11 theme scenario 849:856 arg1 necessary 903:911 necessary 903:911 necessary 903:911 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 2 12 from frequency 325:333 arg1 individuals 390:400 immunocompetent individuals 374:400 immunocompetent individuals with a healthy background 374:426 Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. 35736250 6 13 theme structural 1141:1150 arg1 nature 1152:1157 a structural nature 1139:1157 a structural nature 1139:1157 Could these be of a structural nature? 35736250 2 14 with individuals 390:400 arg1 background 417:426 a healthy background 407:426 a healthy background 407:426 Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. 35736250 3 15 theme few 452:454 arg1 years 456:460 the past few years 443:460 the past few years 443:460 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 2 16 theme fungal 268:273 arg1 infections 275:284 most fungal infections 263:284 most fungal infections 263:284 Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. 35736250 2 17 theme forms 365:369 arg1 frequency 325:333 the lower frequency 315:333 the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background 315:426 Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. 35736250 2 18 theme immunocompetent 374:388 arg1 individuals 390:400 immunocompetent individuals 374:400 immunocompetent individuals with a healthy background 374:426 Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. 35736250 0 19 theme Pathogenic 88:97 arg1 Adaptation 99:108 Pathogenic Adaptation 88:108 Pathogenic Adaptation 88:108 The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation. 35736250 2 20 theme most 263:266 arg1 infections 275:284 most fungal infections 263:284 most fungal infections 263:284 Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. 35736250 7 21 theme fungal 1303:1308 arg1 species 1310:1316 pathogenic fungal species 1292:1316 pathogenic fungal species 1292:1316 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 0 22 theme Sweet 4:8 arg1 Side 10:13 The Sweet Side 0:13 The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation. 0:109 The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation. 35736250 3 23 theme greater 695:701 arg1 emergence 703:711 the greater emergence 691:711 the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus 691:811 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 7 24 theme infections 1376:1385 arg1 severity 1358:1365 increasing severity 1347:1365 increasing severity of these infections 1347:1385 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 1 25 theme debilitated 173:183 arg1 individuals 185:195 debilitated individuals 173:195 debilitated individuals 173:195 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 3 26 theme fungal 732:737 arg1 variants 739:746 more pathogenic fungal variants 716:746 more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus 716:811 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 4 27 theme increased 972:980 arg1 incidence 982:990 the increased incidence 968:990 the increased incidence of fungal infection 968:1010 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 4 28 theme infection 1002:1010 arg1 incidence 982:990 the increased incidence 968:990 the increased incidence of fungal infection 968:1010 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 3 29 theme variants 739:746 arg1 regions 679:685 previously infrequent regions 657:685 previously infrequent regions 657:685 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 3 29 theme variants 739:746 arg1 emergence 703:711 the greater emergence 691:711 the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus 691:811 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 3 30 from cases 471:475 arg1 individuals 516:526 healthy individuals 508:526 healthy individuals 508:526 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 2 31 theme healthy 409:415 arg1 background 417:426 a healthy background 407:426 a healthy background 407:426 Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. 35736250 4 32 theme fungal 995:1000 arg1 infection 1002:1010 fungal infection 995:1010 fungal infection 995:1010 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 2 33 dep severe 349:354 arg1 clinical 356:363 clinical 356:363 clinical 356:363 Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. 35736250 3 34 dep such 779:782 arg1 as 784:785 as 784:785 as 784:785 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 3 35 theme severe 480:485 arg1 infections 494:503 severe fungal infections 480:503 severe fungal infections 480:503 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 3 36 theme fungal 487:492 arg1 infections 494:503 severe fungal infections 480:503 severe fungal infections 480:503 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 0 37 theme Infections 25:34 arg1 Side 10:13 The Sweet Side 0:13 The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation. 0:109 The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation. 35736250 2 38 theme lower 319:323 arg1 frequency 325:333 the lower frequency 315:333 the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background 315:426 Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. 35736250 7 39 theme increasing 1347:1356 arg1 severity 1358:1365 increasing severity 1347:1365 increasing severity of these infections 1347:1385 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 7 40 theme glycoconjugate 1244:1257 arg1 composition 1259:1269 glycoconjugate composition 1244:1269 glycoconjugate composition 1244:1269 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 0 41 theme Fungal 18:23 arg1 Infections 25:34 Fungal Infections 18:34 Fungal Infections 18:34 The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation. 35736250 4 42 dep scenario 849:856 arg1 the 832:834 the 832:834 the 832:834 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 4 42 dep scenario 849:856 arg1 arrival 836:842 arrival 836:842 arrival 836:842 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 7 43 theme pathogenic 1292:1301 arg1 species 1310:1316 pathogenic fungal species 1292:1316 pathogenic fungal species 1292:1316 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 7 44 theme severity 1358:1365 arg1 scenario 1335:1342 the current scenario 1323:1342 the current scenario of increasing severity of these infections 1323:1385 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 7 45 theme composition 1259:1269 arg1 factors 1233:1239 the virulence factors 1219:1239 the virulence factors of glycoconjugate composition 1219:1269 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 0 46 theme Structural 37:46 arg1 Diversity 55:63 Structural Glycan Diversity 37:63 Structural Glycan Diversity 37:63 The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation. 35736250 4 47 theme severe 871:876 arg1 infections 885:894 prevalent severe fungal infections 861:894 prevalent severe fungal infections 861:894 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 7 48 theme species 1310:1316 arg1 adaptation 1278:1287 the adaptation 1274:1287 the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections 1274:1385 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 3 49 theme several 463:469 arg1 cases 471:475 several cases 463:475 several cases of severe fungal infections in healthy individuals 463:526 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 4 50 theme prevalent 861:869 arg1 infections 885:894 prevalent severe fungal infections 861:894 prevalent severe fungal infections 861:894 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 3 51 theme epidemiological 558:572 arg1 dynamics 574:581 the epidemiological dynamics 554:581 the epidemiological dynamics of fungal infections 554:602 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 7 52 theme factors 1233:1239 arg1 importance 1205:1214 the importance 1201:1214 the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections 1201:1385 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 1 53 theme Fungal 111:116 arg1 infections 118:127 Fungal infections 111:127 Fungal infections 111:127 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 1 53 theme Fungal 111:116 arg1 infections 159:168 the most common secondary infections 133:168 the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression 133:246 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 3 54 theme healthy 758:764 arg1 individuals 766:776 healthy individuals 758:776 healthy individuals 758:776 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 4 55 theme infections 885:894 arg1 scenario 849:856 a scenario 847:856 a scenario of prevalent severe fungal infections 847:894 Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. 35736250 1 56 theme chronic 211:217 arg1 disease 219:225 chronic disease 211:225 chronic disease 211:225 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 3 57 theme healthy 508:514 arg1 individuals 516:526 healthy individuals 508:526 healthy individuals 508:526 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 0 58 dep Side 10:13 arg1 Diversity 55:63 Structural Glycan Diversity 37:63 Structural Glycan Diversity 37:63 The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation. 35736250 0 58 dep Side 10:13 arg1 Importance 73:82 Its Importance 69:82 Its Importance for Pathogenic Adaptation 69:108 The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation. 35736250 7 59 theme virulence 1223:1231 arg1 factors 1233:1239 the virulence factors 1219:1239 the virulence factors of glycoconjugate composition 1219:1269 Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections. 35736250 3 60 from change 544:549 arg1 dynamics 574:581 the epidemiological dynamics 554:581 the epidemiological dynamics of fungal infections 554:602 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 1 61 theme disease 219:225 arg1 state 202:206 a state 200:206 a state of chronic disease or immunosuppression 200:246 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 3 62 theme recurrent 634:642 arg1 outbreaks 644:652 recurrent outbreaks 634:652 recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus 634:811 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 3 63 theme fungal 586:591 arg1 infections 593:602 fungal infections 586:602 fungal infections 586:602 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 3 64 theme past 447:450 arg1 years 456:460 the past few years 443:460 the past few years 443:460 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 2 65 theme severe 349:354 arg1 forms 365:369 their more severe clinical forms 338:369 their more severe clinical forms 338:369 Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. 35736250 0 66 theme Glycan 48:53 arg1 Diversity 55:63 Structural Glycan Diversity 37:63 Structural Glycan Diversity 37:63 The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation. 35736250 3 67 theme infections 593:602 arg1 dynamics 574:581 the epidemiological dynamics 554:581 the epidemiological dynamics of fungal infections 554:602 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 1 68 from infections 159:168 arg1 individuals 185:195 debilitated individuals 173:195 debilitated individuals 173:195 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 1 68 from infections 159:168 arg1 state 202:206 a state 200:206 a state of chronic disease or immunosuppression 200:246 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 35736250 3 69 theme infections 494:503 arg1 cases 471:475 several cases 463:475 several cases of severe fungal infections in healthy individuals 463:526 However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. 35736250 1 70 theme immunosuppression 230:246 arg1 state 202:206 a state 200:206 a state of chronic disease or immunosuppression 200:246 Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. 36388604 0 0 theme cell 82:85 arg1 wall 87:90 the cell wall 78:90 the cell wall purified with primary plasmodesmata 78:126 Enzymatic fingerprinting reveals specific xyloglucan and pectin signatures in the cell wall purified with primary plasmodesmata. 36388604 4 1 theme subcellular 533:543 arg1 fractionation 545:557 subcellular fractionation 533:557 subcellular fractionation 533:557 To achieve this result we combined subcellular fractionation, polysaccharide analyses and enzymatic fingerprinting approaches. 36388604 1 2 theme neighbouring 162:173 arg1 cells 181:185 neighbouring plant cells 162:185 neighbouring plant cells 162:185 Plasmodesmata (PD) pores connect neighbouring plant cells and enable direct transport across the cell wall. 36388604 6 3 dep fucosylated 782:792 arg1 possibly 743:750 possibly 743:750 possibly 743:750 Most xyloglucans, although possibly not abundant as a group, were fucosylated. 36388604 6 4 gly fucosylated 782:792 arg1 xyloglucans 721:731 Most xyloglucans 716:731 Most xyloglucans 716:731 Most xyloglucans, although possibly not abundant as a group, were fucosylated. 36388604 8 5 theme Full 911:914 arg1 forms 938:942 Full rhamnogalacturonan II forms 911:942 Full rhamnogalacturonan II forms 911:942 Full rhamnogalacturonan II forms, highly methyl-acetylated, were also present. 36388604 10 6 theme wall 1230:1233 arg1 polysaccharides 1235:1249 wall polysaccharides 1230:1249 wall polysaccharides associated with PD 1230:1268 Overall, the protocol and the data presented here open new opportunities for the study of wall polysaccharides associated with PD. 36388604 9 7 theme time 1117:1120 arg1 interval 1122:1129 a time interval 1115:1129 a time interval of days 1115:1137 We additionally showed that these domains, compared to the broad wall, are less affected by wall modifying activities during a time interval of days. 36388604 5 8 theme wall 658:661 arg1 rest 641:644 the rest 637:644 the rest of the cell wall 637:661 Relative to the rest of the cell wall, specific patterns were observed in the PD fraction. 36388604 5 9 theme cell 653:656 arg1 wall 658:661 the cell wall 649:661 the cell wall 649:661 Relative to the rest of the cell wall, specific patterns were observed in the PD fraction. 36388604 2 10 theme structures 286:295 arg1 composition 265:275 the molecular composition 251:275 the molecular composition of these structures 251:295 Understanding the molecular composition of these structures is essential to address their formation and later dynamic regulation. 36388604 8 11 theme II 935:936 arg1 forms 938:942 Full rhamnogalacturonan II forms 911:942 Full rhamnogalacturonan II forms 911:942 Full rhamnogalacturonan II forms, highly methyl-acetylated, were also present. 36388604 1 12 theme plant 175:179 arg1 cells 181:185 neighbouring plant cells 162:185 neighbouring plant cells 162:185 Plasmodesmata (PD) pores connect neighbouring plant cells and enable direct transport across the cell wall. 36388604 0 13 theme primary 106:112 arg1 plasmodesmata 114:126 primary plasmodesmata 106:126 primary plasmodesmata 106:126 Enzymatic fingerprinting reveals specific xyloglucan and pectin signatures in the cell wall purified with primary plasmodesmata. 36388604 9 14 theme broad 1049:1053 arg1 wall 1055:1058 the broad wall 1045:1058 the broad wall 1045:1058 We additionally showed that these domains, compared to the broad wall, are less affected by wall modifying activities during a time interval of days. 36388604 4 15 theme fingerprinting 598:611 arg1 approaches 613:622 enzymatic fingerprinting approaches 588:622 enzymatic fingerprinting approaches 588:622 To achieve this result we combined subcellular fractionation, polysaccharide analyses and enzymatic fingerprinting approaches. 36388604 5 16 theme specific 664:671 arg1 patterns 673:680 specific patterns 664:680 specific patterns 664:680 Relative to the rest of the cell wall, specific patterns were observed in the PD fraction. 36388604 9 17 theme days 1134:1137 arg1 interval 1122:1129 a time interval 1115:1129 a time interval of days 1115:1137 We additionally showed that these domains, compared to the broad wall, are less affected by wall modifying activities during a time interval of days. 36388604 0 18 theme Enzymatic 0:8 arg1 fingerprinting 10:23 Enzymatic fingerprinting 0:23 Enzymatic fingerprinting 0:23 Enzymatic fingerprinting reveals specific xyloglucan and pectin signatures in the cell wall purified with primary plasmodesmata. 36388604 4 19 theme enzymatic 588:596 arg1 approaches 613:622 enzymatic fingerprinting approaches 588:622 enzymatic fingerprinting approaches 588:622 To achieve this result we combined subcellular fractionation, polysaccharide analyses and enzymatic fingerprinting approaches. 36388604 6 20 dep possibly 743:750 arg1 abundant 756:763 abundant 756:763 abundant 756:763 Most xyloglucans, although possibly not abundant as a group, were fucosylated. 36388604 0 21 theme pectin 57:62 arg1 signatures 64:73 specific xyloglucan and pectin signatures 33:73 specific xyloglucan and pectin signatures 33:73 Enzymatic fingerprinting reveals specific xyloglucan and pectin signatures in the cell wall purified with primary plasmodesmata. 36388604 3 22 theme primary 448:454 arg1 PD 456:457 primary PD 448:457 primary PD of Arabidopsis thaliana cell cultures 448:495 Here we provide a biochemical characterisation of the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures. 36388604 0 23 theme specific 33:40 arg1 signatures 64:73 specific xyloglucan and pectin signatures 33:73 specific xyloglucan and pectin signatures 33:73 Enzymatic fingerprinting reveals specific xyloglucan and pectin signatures in the cell wall purified with primary plasmodesmata. 36388604 7 24 theme rhamnogalacturonan 856:873 arg1 species 877:883 rhamnogalacturonan I species 856:883 rhamnogalacturonan I species 856:883 Homogalacturonans displayed short methylated stretches while rhamnogalacturonan I species were remarkably abundant. 36388604 8 25 theme methyl-acetylated 952:968 arg1 forms 938:942 Full rhamnogalacturonan II forms 911:942 Full rhamnogalacturonan II forms 911:942 Full rhamnogalacturonan II forms, highly methyl-acetylated, were also present. 36388604 3 26 theme cell 483:486 arg1 cultures 488:495 Arabidopsis thaliana cell cultures 462:495 Arabidopsis thaliana cell cultures 462:495 Here we provide a biochemical characterisation of the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures. 36388604 3 27 theme biochemical 385:395 arg1 characterisation 397:412 a biochemical characterisation 383:412 a biochemical characterisation of the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures 383:495 Here we provide a biochemical characterisation of the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures. 36388604 7 28 theme methylated 829:838 arg1 stretches 840:848 short methylated stretches 823:848 short methylated stretches 823:848 Homogalacturonans displayed short methylated stretches while rhamnogalacturonan I species were remarkably abundant. 36388604 7 29 theme I 875:875 arg1 species 877:883 rhamnogalacturonan I species 856:883 rhamnogalacturonan I species 856:883 Homogalacturonans displayed short methylated stretches while rhamnogalacturonan I species were remarkably abundant. 36388604 3 30 theme cultures 488:495 arg1 PD 456:457 primary PD 448:457 primary PD of Arabidopsis thaliana cell cultures 448:495 Here we provide a biochemical characterisation of the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures. 36388604 3 31 theme wall 426:429 arg1 characterisation 397:412 a biochemical characterisation 383:412 a biochemical characterisation of the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures 383:495 Here we provide a biochemical characterisation of the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures. 36388604 2 32 theme dynamic 347:353 arg1 regulation 355:364 later dynamic regulation 341:364 later dynamic regulation 341:364 Understanding the molecular composition of these structures is essential to address their formation and later dynamic regulation. 36388604 8 33 theme rhamnogalacturonan 916:933 arg1 forms 938:942 Full rhamnogalacturonan II forms 911:942 Full rhamnogalacturonan II forms 911:942 Full rhamnogalacturonan II forms, highly methyl-acetylated, were also present. 36388604 3 34 theme Arabidopsis 462:472 arg1 cultures 488:495 Arabidopsis thaliana cell cultures 462:495 Arabidopsis thaliana cell cultures 462:495 Here we provide a biochemical characterisation of the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures. 36388604 0 35 theme xyloglucan 42:51 arg1 signatures 64:73 specific xyloglucan and pectin signatures 33:73 specific xyloglucan and pectin signatures 33:73 Enzymatic fingerprinting reveals specific xyloglucan and pectin signatures in the cell wall purified with primary plasmodesmata. 36388604 10 36 theme new 1195:1197 arg1 opportunities 1199:1211 new opportunities 1195:1211 new opportunities for the study of wall polysaccharides associated with PD 1195:1268 Overall, the protocol and the data presented here open new opportunities for the study of wall polysaccharides associated with PD. 36388604 10 37 theme polysaccharides 1235:1249 arg1 study 1221:1225 the study 1217:1225 the study of wall polysaccharides associated with PD 1217:1268 Overall, the protocol and the data presented here open new opportunities for the study of wall polysaccharides associated with PD. 36388604 4 38 dep combined 524:531 arg1 achieve 501:507 achieve 501:507 To achieve this result 498:519 To achieve this result we combined subcellular fractionation, polysaccharide analyses and enzymatic fingerprinting approaches. 36388604 5 39 theme PD 703:704 arg1 fraction 706:713 the PD fraction 699:713 the PD fraction 699:713 Relative to the rest of the cell wall, specific patterns were observed in the PD fraction. 36388604 3 40 theme cell 421:424 arg1 wall 426:429 the cell wall 417:429 the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures 417:495 Here we provide a biochemical characterisation of the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures. 36388604 1 41 theme Plasmodesmata 129:141 arg1 pores 148:152 Plasmodesmata (PD) pores 129:152 Plasmodesmata (PD) pores 129:152 Plasmodesmata (PD) pores connect neighbouring plant cells and enable direct transport across the cell wall. 36388604 5 42 located observed 687:694 arg2 patterns 673:680 specific patterns 664:680 specific patterns 664:680 Relative to the rest of the cell wall, specific patterns were observed in the PD fraction. 36388604 5 42 located observed 687:694 arg1 fraction 706:713 the PD fraction 699:713 the PD fraction 699:713 Relative to the rest of the cell wall, specific patterns were observed in the PD fraction. 36388604 4 43 theme polysaccharide 560:573 arg1 analyses 575:582 polysaccharide analyses 560:582 polysaccharide analyses 560:582 To achieve this result we combined subcellular fractionation, polysaccharide analyses and enzymatic fingerprinting approaches. 36388604 3 44 dep Arabidopsis 462:472 arg1 thaliana 474:481 thaliana 474:481 thaliana 474:481 Here we provide a biochemical characterisation of the cell wall co-purified with primary PD of Arabidopsis thaliana cell cultures. 36388604 6 45 theme Most 716:719 arg1 xyloglucans 721:731 Most xyloglucans 716:731 Most xyloglucans 716:731 Most xyloglucans, although possibly not abundant as a group, were fucosylated. 36388604 2 46 theme later 341:345 arg1 regulation 355:364 later dynamic regulation 341:364 later dynamic regulation 341:364 Understanding the molecular composition of these structures is essential to address their formation and later dynamic regulation. 36388604 1 47 theme cell 226:229 arg1 wall 231:234 the cell wall 222:234 the cell wall 222:234 Plasmodesmata (PD) pores connect neighbouring plant cells and enable direct transport across the cell wall. 36388604 2 48 theme molecular 255:263 arg1 composition 265:275 the molecular composition 251:275 the molecular composition of these structures 251:295 Understanding the molecular composition of these structures is essential to address their formation and later dynamic regulation. 36388604 1 49 theme direct 198:203 arg1 transport 205:213 direct transport 198:213 direct transport across the cell wall 198:234 Plasmodesmata (PD) pores connect neighbouring plant cells and enable direct transport across the cell wall. 36388604 9 50 theme wall 1082:1085 arg1 activities 1097:1106 wall modifying activities 1082:1106 wall modifying activities 1082:1106 We additionally showed that these domains, compared to the broad wall, are less affected by wall modifying activities during a time interval of days. 36388604 9 51 theme modifying 1087:1095 arg1 activities 1097:1106 wall modifying activities 1082:1106 wall modifying activities 1082:1106 We additionally showed that these domains, compared to the broad wall, are less affected by wall modifying activities during a time interval of days. 36388604 7 52 theme short 823:827 arg1 stretches 840:848 short methylated stretches 823:848 short methylated stretches 823:848 Homogalacturonans displayed short methylated stretches while rhamnogalacturonan I species were remarkably abundant. 36283665 0 0 theme membrane 81:88 arg1 fouling 90:96 membrane fouling 81:96 membrane fouling in bioreactors 81:111 Study on the performance and mechanism of bio-electrochemical system to mitigate membrane fouling in bioreactors. 36283665 4 1 theme control 675:681 arg1 group 683:687 the control group 671:687 the control group 671:687 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 1 2 theme system 241:246 arg1 anode 208:212 the anode 204:212 the anode of the bio-electrochemical system 204:246 To alleviate membrane fouling, a membrane of the membrane bioreactor was directly used as the anode of the bio-electrochemical system. 36283665 1 2 theme system 241:246 arg1 membrane 147:154 a membrane 145:154 a membrane of the membrane bioreactor 145:181 To alleviate membrane fouling, a membrane of the membrane bioreactor was directly used as the anode of the bio-electrochemical system. 36283665 7 3 theme polysaccharides 1171:1185 arg1 degradation 1156:1166 the degradation 1152:1166 the degradation of polysaccharides 1152:1185 Two-dimensional correlation spectroscopy showed that electrons promote the degradation of polysaccharides, thereby alleviating membrane fouling. 36283665 0 4 from Study 0:4 arg1 mechanism 29:37 mechanism 29:37 mechanism 29:37 Study on the performance and mechanism of bio-electrochemical system to mitigate membrane fouling in bioreactors. 36283665 0 4 from Study 0:4 arg1 performance 13:23 performance 13:23 performance 13:23 Study on the performance and mechanism of bio-electrochemical system to mitigate membrane fouling in bioreactors. 36283665 4 5 theme long-chain 743:752 arg1 derivatives 760:770 long-chain ester derivatives 743:770 long-chain ester derivatives 743:770 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 4 6 theme Three-dimensional 548:564 arg1 spectroscopy 579:590 Three-dimensional fluorescence spectroscopy 548:590 Three-dimensional fluorescence spectroscopy 548:590 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 5 7 theme cake 922:925 arg1 layer 927:931 the cake layer 918:931 the cake layer 918:931 Therefore, current (electrons) can change the composition of the cake layer. 36283665 6 8 theme electroactive 1012:1024 arg1 microorganisms 1026:1039 electroactive microorganisms 1012:1039 electroactive microorganisms 1012:1039 High-throughput sequencing indicated that a significantly higher abundance of electroactive microorganisms on the experimental than control group. 36283665 3 9 theme open-circuit 445:456 arg1 group 458:462 the open-circuit group 441:462 the open-circuit group 441:462 The polysaccharide and protein concentrations in the open-circuit group were 4.2 and 2.9 times higher than those in the closed-circuit group, respectively. 36283665 6 10 theme control 1066:1072 arg1 group 1074:1078 the experimental than control group 1044:1078 the experimental than control group 1044:1078 High-throughput sequencing indicated that a significantly higher abundance of electroactive microorganisms on the experimental than control group. 36283665 1 11 theme bioreactor 172:181 arg1 anode 208:212 the anode 204:212 the anode of the bio-electrochemical system 204:246 To alleviate membrane fouling, a membrane of the membrane bioreactor was directly used as the anode of the bio-electrochemical system. 36283665 1 11 theme bioreactor 172:181 arg1 membrane 147:154 a membrane 145:154 a membrane of the membrane bioreactor 145:181 To alleviate membrane fouling, a membrane of the membrane bioreactor was directly used as the anode of the bio-electrochemical system. 36283665 4 12 theme fluorescence 566:577 arg1 spectroscopy 579:590 Three-dimensional fluorescence spectroscopy 548:590 Three-dimensional fluorescence spectroscopy 548:590 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 4 13 from deposition 657:666 arg1 group 683:687 the control group 671:687 the control group 671:687 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 1 14 theme membrane 163:170 arg1 bioreactor 172:181 the membrane bioreactor 159:181 the membrane bioreactor 159:181 To alleviate membrane fouling, a membrane of the membrane bioreactor was directly used as the anode of the bio-electrochemical system. 36283665 4 15 contain contained 689:697 arg1 deposition 657:666 the deposition 653:666 the deposition in the control group 653:687 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 4 15 contain contained 689:697 arg2 compounds 721:729 high-molecular-weight compounds 699:729 high-molecular-weight compounds 699:729 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 4 15 contain contained 689:697 arg2 derivatives 760:770 long-chain ester derivatives 743:770 long-chain ester derivatives 743:770 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 4 15 contain contained 689:697 arg2 hydrocarbons 794:805 complex hydrocarbons 786:805 complex hydrocarbons 786:805 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 4 15 contain contained 689:697 arg1 most 645:648 most 645:648 most 645:648 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 4 15 contain contained 689:697 arg2 phenols 773:779 phenols 773:779 phenols 773:779 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 3 16 theme closed-circuit 512:525 arg1 group 527:531 the closed-circuit group 508:531 the closed-circuit group 508:531 The polysaccharide and protein concentrations in the open-circuit group were 4.2 and 2.9 times higher than those in the closed-circuit group, respectively. 36283665 2 17 theme 0.44 mA 344:350 arg1 current 333:339 a current 331:339 a current of 0.44 mA, the increase in ΔTMP 331:372 On the 14th day, the control group had blocked, while the experimental group with a current of 0.44 mA, the increase in ΔTMP was only 2.2 kPa. 36283665 6 18 from abundance 999:1007 arg1 group 1074:1078 the experimental than control group 1044:1078 the experimental than control group 1044:1078 High-throughput sequencing indicated that a significantly higher abundance of electroactive microorganisms on the experimental than control group. 36283665 5 19 theme layer 927:931 arg1 composition 903:913 the composition 899:913 the composition of the cake layer 899:931 Therefore, current (electrons) can change the composition of the cake layer. 36283665 7 20 theme correlation 1097:1107 arg1 spectroscopy 1109:1120 Two-dimensional correlation spectroscopy 1081:1120 Two-dimensional correlation spectroscopy 1081:1120 Two-dimensional correlation spectroscopy showed that electrons promote the degradation of polysaccharides, thereby alleviating membrane fouling. 36283665 4 21 theme ester 754:758 arg1 derivatives 760:770 long-chain ester derivatives 743:770 long-chain ester derivatives 743:770 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 3 22 theme protein 415:421 arg1 higher 487:492 higher 487:492 higher 487:492 The polysaccharide and protein concentrations in the open-circuit group were 4.2 and 2.9 times higher than those in the closed-circuit group, respectively. 36283665 3 22 theme protein 415:421 arg1 concentrations 423:436 The polysaccharide and protein concentrations 392:436 concentrations 423:436 The polysaccharide and protein concentrations in the open-circuit group were 4.2 and 2.9 times higher than those in the closed-circuit group, respectively. 36283665 2 23 theme control 270:276 arg1 group 278:282 the control group 266:282 the control group 266:282 On the 14th day, the control group had blocked, while the experimental group with a current of 0.44 mA, the increase in ΔTMP was only 2.2 kPa. 36283665 4 24 theme chromatography 600:613 arg1 spectrometry 620:631 gas chromatography mass spectrometry 596:631 gas chromatography mass spectrometry 596:631 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 6 25 theme than 1061:1064 arg1 group 1074:1078 the experimental than control group 1044:1078 the experimental than control group 1044:1078 High-throughput sequencing indicated that a significantly higher abundance of electroactive microorganisms on the experimental than control group. 36283665 4 26 dep showed 633:638 arg1 whereas 808:814 whereas 808:814 whereas 808:814 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 3 27 theme polysaccharide 396:409 arg1 higher 487:492 higher 487:492 higher 487:492 The polysaccharide and protein concentrations in the open-circuit group were 4.2 and 2.9 times higher than those in the closed-circuit group, respectively. 36283665 3 27 theme polysaccharide 396:409 arg1 concentrations 423:436 The polysaccharide and protein concentrations 392:436 concentrations 423:436 The polysaccharide and protein concentrations in the open-circuit group were 4.2 and 2.9 times higher than those in the closed-circuit group, respectively. 36283665 7 28 theme membrane 1208:1215 arg1 fouling 1217:1223 membrane fouling 1208:1223 membrane fouling 1208:1223 Two-dimensional correlation spectroscopy showed that electrons promote the degradation of polysaccharides, thereby alleviating membrane fouling. 36283665 6 29 theme High-throughput 934:948 arg1 sequencing 950:959 High-throughput sequencing 934:959 High-throughput sequencing 934:959 High-throughput sequencing indicated that a significantly higher abundance of electroactive microorganisms on the experimental than control group. 36283665 7 30 theme Two-dimensional 1081:1095 arg1 spectroscopy 1109:1120 Two-dimensional correlation spectroscopy 1081:1120 Two-dimensional correlation spectroscopy 1081:1120 Two-dimensional correlation spectroscopy showed that electrons promote the degradation of polysaccharides, thereby alleviating membrane fouling. 36283665 6 31 theme microorganisms 1026:1039 arg1 abundance 999:1007 a significantly higher abundance 976:1007 a significantly higher abundance of electroactive microorganisms on the experimental than control group 976:1078 High-throughput sequencing indicated that a significantly higher abundance of electroactive microorganisms on the experimental than control group. 36283665 6 32 theme experimental 1048:1059 arg1 group 1074:1078 the experimental than control group 1044:1078 the experimental than control group 1044:1078 High-throughput sequencing indicated that a significantly higher abundance of electroactive microorganisms on the experimental than control group. 36283665 0 33 theme bio-electrochemical 42:60 arg1 system 62:67 bio-electrochemical system 42:67 bio-electrochemical system 42:67 Study on the performance and mechanism of bio-electrochemical system to mitigate membrane fouling in bioreactors. 36283665 1 34 used used 196:199 arg2 anode 208:212 the anode 204:212 the anode of the bio-electrochemical system 204:246 To alleviate membrane fouling, a membrane of the membrane bioreactor was directly used as the anode of the bio-electrochemical system. 36283665 1 34 used used 196:199 arg2 membrane 147:154 a membrane 145:154 a membrane of the membrane bioreactor 145:181 To alleviate membrane fouling, a membrane of the membrane bioreactor was directly used as the anode of the bio-electrochemical system. 36283665 2 35 theme experimental 307:318 arg1 2.2 kPa 383:389 2.2 kPa 383:389 2.2 kPa 383:389 On the 14th day, the control group had blocked, while the experimental group with a current of 0.44 mA, the increase in ΔTMP was only 2.2 kPa. 36283665 2 35 theme experimental 307:318 arg1 group 320:324 the experimental group 303:324 the experimental group with a current of 0.44 mA, the increase in ΔTMP 303:372 On the 14th day, the control group had blocked, while the experimental group with a current of 0.44 mA, the increase in ΔTMP was only 2.2 kPa. 36283665 6 36 dep indicated 961:969 arg1 abundance 999:1007 a significantly higher abundance 976:1007 a significantly higher abundance of electroactive microorganisms on the experimental than control group 976:1078 High-throughput sequencing indicated that a significantly higher abundance of electroactive microorganisms on the experimental than control group. 36283665 4 37 theme experimental 820:831 arg1 opposite 847:854 opposite 847:854 opposite 847:854 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 4 37 theme experimental 820:831 arg1 group 833:837 the experimental group 816:837 the experimental group 816:837 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 2 38 with group 320:324 arg1 current 333:339 a current 331:339 a current of 0.44 mA, the increase in ΔTMP 331:372 On the 14th day, the control group had blocked, while the experimental group with a current of 0.44 mA, the increase in ΔTMP was only 2.2 kPa. 36283665 0 39 dep performance 13:23 arg1 the 9:11 the 9:11 the 9:11 Study on the performance and mechanism of bio-electrochemical system to mitigate membrane fouling in bioreactors. 36283665 3 40 from concentrations 423:436 arg1 group 458:462 the open-circuit group 441:462 the open-circuit group 441:462 The polysaccharide and protein concentrations in the open-circuit group were 4.2 and 2.9 times higher than those in the closed-circuit group, respectively. 36283665 1 41 theme membrane 127:134 arg1 fouling 136:142 membrane fouling 127:142 membrane fouling 127:142 To alleviate membrane fouling, a membrane of the membrane bioreactor was directly used as the anode of the bio-electrochemical system. 36283665 6 42 theme higher 992:997 arg1 abundance 999:1007 a significantly higher abundance 976:1007 a significantly higher abundance of electroactive microorganisms on the experimental than control group 976:1078 High-throughput sequencing indicated that a significantly higher abundance of electroactive microorganisms on the experimental than control group. 36283665 4 43 theme high-molecular-weight 699:719 arg1 compounds 721:729 high-molecular-weight compounds 699:729 high-molecular-weight compounds 699:729 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 4 44 theme complex 786:792 arg1 hydrocarbons 794:805 complex hydrocarbons 786:805 complex hydrocarbons 786:805 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 0 45 from fouling 90:96 arg1 bioreactors 101:111 bioreactors 101:111 bioreactors 101:111 Study on the performance and mechanism of bio-electrochemical system to mitigate membrane fouling in bioreactors. 36283665 2 46 from increase 357:364 arg1 ΔTMP 369:372 ΔTMP 369:372 ΔTMP 369:372 On the 14th day, the control group had blocked, while the experimental group with a current of 0.44 mA, the increase in ΔTMP was only 2.2 kPa. 36283665 4 47 theme gas 596:598 arg1 spectrometry 620:631 gas chromatography mass spectrometry 596:631 gas chromatography mass spectrometry 596:631 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 0 48 theme system 62:67 arg1 mechanism 29:37 mechanism 29:37 mechanism 29:37 Study on the performance and mechanism of bio-electrochemical system to mitigate membrane fouling in bioreactors. 36283665 0 48 theme system 62:67 arg1 performance 13:23 performance 13:23 performance 13:23 Study on the performance and mechanism of bio-electrochemical system to mitigate membrane fouling in bioreactors. 36283665 4 49 theme mass 615:618 arg1 spectrometry 620:631 gas chromatography mass spectrometry 596:631 gas chromatography mass spectrometry 596:631 Three-dimensional fluorescence spectroscopy and gas chromatography mass spectrometry showed that most of the deposition in the control group contained high-molecular-weight compounds, especially long-chain ester derivatives, phenols, and complex hydrocarbons, whereas the experimental group was the opposite. 36283665 1 50 theme bio-electrochemical 221:239 arg1 system 241:246 the bio-electrochemical system 217:246 the bio-electrochemical system 217:246 To alleviate membrane fouling, a membrane of the membrane bioreactor was directly used as the anode of the bio-electrochemical system. 36838323 0 0 theme Feed 86:89 arg1 Intake 91:96 Divergent Residual Feed Intake 67:96 Divergent Residual Feed Intake 67:96 Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake. 36838323 2 1 theme high 449:452 arg1 groups 476:481 the extremely high and extremely low RFI groups 435:481 the extremely high and extremely low RFI groups 435:481 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 4 2 theme group 801:805 arg1 biomarkers 769:778 potential biomarkers 759:778 potential biomarkers of the HRFI and LRFI group 759:805 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 0 3 with Characteristics 27:41 arg1 Intake 91:96 Divergent Residual Feed Intake 67:96 Divergent Residual Feed Intake 67:96 Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake. 36838323 0 4 theme Residual 77:84 arg1 Intake 91:96 Divergent Residual Feed Intake 67:96 Divergent Residual Feed Intake 67:96 Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake. 36838323 2 5 from five 419:422 arg1 each 427:430 each 427:430 each 427:430 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 5 from five 419:422 arg1 groups 476:481 the extremely high and extremely low RFI groups 435:481 the extremely high and extremely low RFI groups 435:481 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 4 6 theme LRFI 796:799 arg1 group 801:805 the HRFI and LRFI group 783:805 group 801:805 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 4 7 theme potential 644:652 arg1 Prevotella 613:622 Prevotella 613:622 Prevotella 613:622 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 4 7 theme potential 644:652 arg1 biomarker 654:662 a potential biomarker 642:662 a potential biomarker in the rumen of the LRFI group 642:693 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 7 8 from differences 1383:1393 arg1 microbes 1398:1405 microbes 1398:1405 microbes 1398:1405 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 7 9 with feces 1322:1326 arg1 RFIs 1358:1361 different RFIs 1348:1361 different RFIs 1348:1361 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 7 10 theme feces 1322:1326 arg1 composition 1297:1307 the microbial composition 1283:1307 the microbial composition of rumen and feces of beef cattle with different RFIs 1283:1361 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 4 11 theme LEfSe 702:706 arg1 method 708:713 the LEfSe method 698:713 the LEfSe method 698:713 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 2 12 theme different 282:290 arg1 RFI 292:294 different RFI 282:294 different RFI 282:294 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 7 13 from variances 1270:1278 arg1 composition 1297:1307 the microbial composition 1283:1307 the microbial composition of rumen and feces of beef cattle with different RFIs 1283:1361 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 6 14 theme expressed 1216:1224 arg1 genes 1226:1230 differentially expressed genes 1201:1230 differentially expressed genes regulating RFI 1201:1245 Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. 36838323 2 15 theme cattle 270:275 arg1 differences 220:230 differences 220:230 differences in the gastrointestinal tract 220:260 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 15 theme cattle 270:275 arg1 characteristics 200:214 the microbial characteristics 186:214 the microbial characteristics 186:214 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 16 from characteristics 200:214 arg1 tract 256:260 the gastrointestinal tract 235:260 the gastrointestinal tract 235:260 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 17 theme RFI 472:474 arg1 groups 476:481 the extremely high and extremely low RFI groups 435:481 the extremely high and extremely low RFI groups 435:481 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 6 18 with microbes 1021:1028 arg1 genes 1054:1058 host genes 1049:1058 host genes 1049:1058 Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. 36838323 2 19 dep cattle 411:416 arg1 five 419:422 five 419:422 five 419:422 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 20 theme beef 265:268 arg1 cattle 270:275 beef cattle 265:275 beef cattle 265:275 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 1 21 theme indicators 140:149 arg1 one 129:131 one 129:131 one 129:131 Residual feed intake (RFI) is one of the indicators of feed efficiency. 36838323 1 21 theme indicators 140:149 arg1 indicators 140:149 the indicators 136:149 the indicators of feed efficiency 136:168 Residual feed intake (RFI) is one of the indicators of feed efficiency. 36838323 2 22 theme low 468:470 arg1 groups 476:481 the extremely high and extremely low RFI groups 435:481 the extremely high and extremely low RFI groups 435:481 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 5 23 theme Functional 831:840 arg1 annotation 842:851 Functional annotation 831:851 Functional annotation 831:851 Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. 36838323 5 24 theme group 907:911 arg1 rumen 889:893 the rumen 885:893 the rumen of the HRFI group 885:911 Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. 36838323 2 25 from differences 220:230 arg1 tract 256:260 the gastrointestinal tract 235:260 the gastrointestinal tract 235:260 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 26 theme rumen 369:373 arg1 characteristics 346:360 the characteristics 342:360 the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups) 342:482 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 4 27 theme LRFI 684:687 arg1 group 689:693 the LRFI group 680:693 the LRFI group 680:693 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 3 28 from phyla 587:591 arg1 feces 606:610 feces 606:610 feces 606:610 The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. 36838323 3 28 from phyla 587:591 arg1 rumen 596:600 rumen 596:600 rumen 596:600 The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. 36838323 1 29 theme feed 154:157 arg1 efficiency 159:168 feed efficiency 154:168 feed efficiency 154:168 Residual feed intake (RFI) is one of the indicators of feed efficiency. 36838323 7 30 theme critical 1418:1425 arg1 role 1427:1430 a critical role 1416:1430 a critical role 1416:1430 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 2 31 with characteristics 200:214 arg1 RFI 292:294 different RFI 282:294 different RFI 282:294 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 4 32 theme HRFI 787:790 arg1 group 801:805 the HRFI and LRFI group 783:805 group 801:805 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 2 33 from characteristics 346:360 arg1 cattle 411:416 10 Qinchuan cattle 399:416 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups) 399:482 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 7 34 theme rumen 1312:1316 arg1 composition 1297:1307 the microbial composition 1283:1307 the microbial composition of rumen and feces of beef cattle with different RFIs 1283:1361 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 1 35 theme efficiency 159:168 arg1 indicators 140:149 the indicators 136:149 the indicators of feed efficiency 136:168 Residual feed intake (RFI) is one of the indicators of feed efficiency. 36838323 0 36 theme Microbiota 16:25 arg1 Characteristics 27:41 Fecal Microbiota Characteristics 10:41 Fecal Microbiota Characteristics 10:41 Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake. 36838323 2 37 used used 326:329 arg2 methodology 310:320 a metagenome methodology 297:320 a metagenome methodology 297:320 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 1 38 theme Residual 99:106 arg1 RFI 121:123 RFI 121:123 RFI 121:123 Residual feed intake (RFI) is one of the indicators of feed efficiency. 36838323 1 38 theme Residual 99:106 arg1 intake 113:118 Residual feed intake 99:118 Residual feed intake (RFI) 99:124 Residual feed intake (RFI) is one of the indicators of feed efficiency. 36838323 2 39 theme 10 399:400 arg1 Qinchuan 402:409 Qinchuan 402:409 Qinchuan 402:409 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 40 theme Qinchuan 402:409 arg1 cattle 411:416 10 Qinchuan cattle 399:416 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups) 399:482 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 41 with differences 220:230 arg1 RFI 292:294 different RFI 282:294 different RFI 282:294 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 5 42 theme HRFI 902:905 arg1 group 907:911 the HRFI group 898:911 the HRFI group 898:911 Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. 36838323 1 43 theme feed 108:111 arg1 RFI 121:123 RFI 121:123 RFI 121:123 Residual feed intake (RFI) is one of the indicators of feed efficiency. 36838323 1 43 theme feed 108:111 arg1 intake 113:118 Residual feed intake 99:118 Residual feed intake (RFI) 99:124 Residual feed intake (RFI) is one of the indicators of feed efficiency. 36838323 7 44 theme beef 1331:1334 arg1 cattle 1336:1341 beef cattle 1331:1341 beef cattle 1331:1341 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 6 45 theme Association 991:1001 arg1 analysis 1003:1010 Association analysis 991:1010 Association analysis of rumen microbes (genus level) with host genes 991:1058 Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. 36838323 2 46 theme microbiota 385:394 arg1 characteristics 346:360 the characteristics 342:360 the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups) 342:482 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 6 47 theme rumen 1015:1019 arg1 microbes 1021:1028 rumen microbes 1015:1028 rumen microbes (genus level) with host genes 1015:1058 Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. 36838323 6 47 theme rumen 1015:1019 arg1 level 1037:1041 genus level 1031:1041 genus level 1031:1041 Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. 36838323 7 48 theme phenotype 1471:1479 arg1 variations 1481:1490 the bovine divergent RFI phenotype variations 1446:1490 the bovine divergent RFI phenotype variations 1446:1490 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 7 49 theme cattle 1336:1341 arg1 rumen 1312:1316 rumen 1312:1316 rumen 1312:1316 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 7 49 theme cattle 1336:1341 arg1 feces 1322:1326 feces 1322:1326 feces of beef cattle with different RFIs 1322:1361 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 4 50 from biomarkers 769:778 arg1 feces 810:814 feces 810:814 feces 810:814 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 2 51 theme fecal 379:383 arg1 microbiota 385:394 fecal microbiota 379:394 fecal microbiota 379:394 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 0 52 theme Cattle 55:60 arg1 Rumen 0:4 Rumen 0:4 Rumen 0:4 Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake. 36838323 0 52 theme Cattle 55:60 arg1 Characteristics 27:41 Fecal Microbiota Characteristics 10:41 Fecal Microbiota Characteristics 10:41 Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake. 36838323 4 53 theme potential 759:767 arg1 biomarkers 769:778 potential biomarkers 759:778 potential biomarkers of the HRFI and LRFI group 759:805 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 7 54 with rumen 1312:1316 arg1 RFIs 1358:1361 different RFIs 1348:1361 different RFIs 1348:1361 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 5 55 theme dietary 946:952 arg1 polysaccharides 954:968 dietary polysaccharides 946:968 dietary polysaccharides 946:968 Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. 36838323 4 56 theme group 689:693 arg1 rumen 671:675 the rumen 667:675 the rumen of the LRFI group 667:693 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 0 57 theme Qinchuan 46:53 arg1 Cattle 55:60 Qinchuan Cattle 46:60 Qinchuan Cattle 46:60 Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake. 36838323 7 58 theme divergent 1457:1465 arg1 variations 1481:1490 the bovine divergent RFI phenotype variations 1446:1490 the bovine divergent RFI phenotype variations 1446:1490 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 2 59 theme microbial 190:198 arg1 characteristics 200:214 the microbial characteristics 186:214 the microbial characteristics 186:214 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 6 60 theme host 1049:1052 arg1 genes 1054:1058 host genes 1049:1058 host genes 1049:1058 Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. 36838323 2 61 dep rumen 369:373 arg1 the 365:367 the 365:367 the 365:367 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 5 62 theme dietary 974:980 arg1 protein 982:988 dietary protein 974:988 dietary protein 974:988 Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. 36838323 3 63 theme dominant 578:585 arg1 Firmicutes 553:562 Firmicutes 553:562 Firmicutes 553:562 The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. 36838323 3 63 theme dominant 578:585 arg1 Bacteroidetes 535:547 Bacteroidetes 535:547 Bacteroidetes 535:547 The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. 36838323 3 63 theme dominant 578:585 arg1 phyla 587:591 the most dominant phyla 569:591 the most dominant phyla in rumen and feces 569:610 The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. 36838323 0 64 with Rumen 0:4 arg1 Intake 91:96 Divergent Residual Feed Intake 67:96 Divergent Residual Feed Intake 67:96 Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake. 36838323 3 65 theme taxonomic 500:508 arg1 annotation 510:519 taxonomic annotation 500:519 taxonomic annotation 500:519 The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. 36838323 7 66 theme different 1348:1356 arg1 RFIs 1358:1361 different RFIs 1348:1361 different RFIs 1348:1361 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 2 67 from rumen 369:373 arg1 cattle 411:416 10 Qinchuan cattle 399:416 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups) 399:482 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 68 theme gastrointestinal 239:254 arg1 tract 256:260 the gastrointestinal tract 235:260 the gastrointestinal tract 235:260 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 69 from microbiota 385:394 arg1 cattle 411:416 10 Qinchuan cattle 399:416 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups) 399:482 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 2 70 theme metagenome 299:308 arg1 methodology 310:320 a metagenome methodology 297:320 a metagenome methodology 297:320 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 5 71 from microbiota 871:880 arg1 rumen 889:893 the rumen 885:893 the rumen of the HRFI group 885:911 Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. 36838323 3 72 theme annotation 510:519 arg1 results 489:495 The results 485:495 The results of taxonomic annotation 485:519 The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. 36838323 0 73 theme Divergent 67:75 arg1 Intake 91:96 Divergent Residual Feed Intake 67:96 Divergent Residual Feed Intake 67:96 Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake. 36838323 5 74 contain had 913:915 arg1 microbiota 871:880 the microbiota 867:880 the microbiota in the rumen of the HRFI group 867:911 Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. 36838323 5 74 contain had 913:915 arg2 ability 927:933 a greater ability 917:933 a greater ability to utilize dietary polysaccharides and dietary protein 917:988 Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. 36838323 5 75 theme greater 919:925 arg1 ability 927:933 a greater ability 917:933 a greater ability to utilize dietary polysaccharides and dietary protein 917:988 Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. 36838323 6 76 theme microbes 1021:1028 arg1 analysis 1003:1010 Association analysis 991:1010 Association analysis of rumen microbes (genus level) with host genes 991:1058 Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. 36838323 7 77 theme microbial 1287:1295 arg1 composition 1297:1307 the microbial composition 1283:1307 the microbial composition of rumen and feces of beef cattle with different RFIs 1283:1361 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 3 78 theme most 573:576 arg1 Firmicutes 553:562 Firmicutes 553:562 Firmicutes 553:562 The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. 36838323 3 78 theme most 573:576 arg1 Bacteroidetes 535:547 Bacteroidetes 535:547 Bacteroidetes 535:547 The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. 36838323 3 78 theme most 573:576 arg1 phyla 587:591 the most dominant phyla 569:591 the most dominant phyla in rumen and feces 569:610 The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. 36838323 2 79 from cattle 411:416 arg1 characteristics 346:360 the characteristics 342:360 the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups) 342:482 To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). 36838323 0 80 theme Fecal 10:14 arg1 Characteristics 27:41 Fecal Microbiota Characteristics 10:41 Fecal Microbiota Characteristics 10:41 Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake. 36838323 7 81 theme RFI 1467:1469 arg1 variations 1481:1490 the bovine divergent RFI phenotype variations 1446:1490 the bovine divergent RFI phenotype variations 1446:1490 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 36838323 6 82 theme genus 1031:1035 arg1 microbes 1021:1028 rumen microbes 1015:1028 rumen microbes (genus level) with host genes 1015:1058 Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. 36838323 6 82 theme genus 1031:1035 arg1 level 1037:1041 genus level 1031:1041 genus level 1031:1041 Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. 36838323 4 83 from biomarker 654:662 arg1 rumen 671:675 the rumen 667:675 the rumen of the LRFI group 667:693 Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. 36838323 7 84 theme bovine 1450:1455 arg1 variations 1481:1490 the bovine divergent RFI phenotype variations 1446:1490 the bovine divergent RFI phenotype variations 1446:1490 This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations. 35835790 3 0 from activity 642:649 arg1 assay 678:682 an enzyme-linked lectin assay 654:682 an enzyme-linked lectin assay 654:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 5 1 from loss 1006:1009 arg1 N1s 1065:1067 current N1s 1057:1067 current N1s 1057:1067 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 4 2 from strains 753:759 arg1 NAs 707:709 NAs 707:709 NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons 707:785 Our results show that NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons are all antigenically similar and distinct from the NA in the H1N1 strain recommended for the 2010-2017 seasons. 35835790 7 3 dep remained 1347:1354 arg1 whereas 1427:1433 whereas 1427:1433 whereas 1427:1433 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 2 4 theme vaccine 452:458 arg1 strains 460:466 recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains 377:466 recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains 377:466 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 4 5 from NA 839:840 arg1 distinct 821:828 distinct 821:828 distinct 821:828 Our results show that NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons are all antigenically similar and distinct from the NA in the H1N1 strain recommended for the 2010-2017 seasons. 35835790 4 5 from NA 839:840 arg1 strain 854:859 the H1N1 strain 845:859 the H1N1 strain recommended for the 2010-2017 seasons 845:897 Our results show that NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons are all antigenically similar and distinct from the NA in the H1N1 strain recommended for the 2010-2017 seasons. 35835790 5 6 theme glycosylation 1026:1038 arg1 site 1040:1043 an N-linked glycosylation site 1014:1043 an N-linked glycosylation site (Asn386) in current N1s 1014:1067 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 6 theme glycosylation 1026:1038 arg1 Asn386 1046:1051 Asn386 1046:1051 Asn386 1046:1051 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 7 theme N-linked 1017:1024 arg1 site 1040:1043 an N-linked glycosylation site 1014:1043 an N-linked glycosylation site (Asn386) in current N1s 1014:1067 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 7 theme N-linked 1017:1024 arg1 Asn386 1046:1051 Asn386 1046:1051 Asn386 1046:1051 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 7 8 theme head 1386:1389 arg1 site 1421:1424 the head domain N-linked glycosylation site 1382:1424 the head domain N-linked glycosylation site 1382:1424 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 3 9 theme % 623:623 arg1 inhibition 625:634 50% inhibition 621:634 50% inhibition of NA activity in an enzyme-linked lectin assay 621:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 0 10 theme circulating 97:107 arg1 strains 109:115 2019-2020 circulating strains 87:115 2019-2020 circulating strains 87:115 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 35835790 3 11 theme enzyme-linked 657:669 arg1 assay 678:682 an enzyme-linked lectin assay 654:682 an enzyme-linked lectin assay 654:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 6 12 theme circulating 1083:1093 arg1 viruses 1100:1106 circulating H3N2 viruses 1083:1106 circulating H3N2 viruses 1083:1106 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 7 13 theme domain 1391:1396 arg1 site 1421:1424 the head domain N-linked glycosylation site 1382:1424 the head domain N-linked glycosylation site 1382:1424 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 6 14 theme vaccine 1126:1132 arg1 strains 1134:1140 the 2020-2021 vaccine strains 1112:1140 the 2020-2021 vaccine strains 1112:1140 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 4 15 from viruses 733:739 arg1 NAs 707:709 NAs 707:709 NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons 707:785 Our results show that NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons are all antigenically similar and distinct from the NA in the H1N1 strain recommended for the 2010-2017 seasons. 35835790 4 16 theme H1N1 728:731 arg1 viruses 733:739 circulating H1N1 viruses 716:739 circulating H1N1 viruses 716:739 Our results show that NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons are all antigenically similar and distinct from the NA in the H1N1 strain recommended for the 2010-2017 seasons. 35835790 7 17 theme N-linked 1398:1405 arg1 site 1421:1424 the head domain N-linked glycosylation site 1382:1424 the head domain N-linked glycosylation site 1382:1424 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 6 18 theme vaccine 1214:1220 arg1 strains 1222:1228 the 2016-2020 vaccine strains 1200:1228 the 2016-2020 vaccine strains 1200:1228 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 4 19 theme vaccine 745:751 arg1 strains 753:759 vaccine strains 745:759 vaccine strains 745:759 Our results show that NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons are all antigenically similar and distinct from the NA in the H1N1 strain recommended for the 2010-2017 seasons. 35835790 6 20 from N2s 1193:1195 arg1 strains 1222:1228 the 2016-2020 vaccine strains 1200:1228 the 2016-2020 vaccine strains 1200:1228 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 3 21 from assay 678:682 arg1 inhibition 625:634 50% inhibition 621:634 50% inhibition of NA activity in an enzyme-linked lectin assay 621:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 5 22 theme current 1057:1063 arg1 N1s 1065:1067 current N1s 1057:1067 current N1s 1057:1067 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 23 from site 1040:1043 arg1 N1s 1065:1067 current N1s 1057:1067 current N1s 1057:1067 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 24 from N1s 1065:1067 arg1 loss 1006:1009 the loss 1002:1009 the loss of an N-linked glycosylation site (Asn386) in current N1s 1002:1067 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 24 from N1s 1065:1067 arg1 accumulation 950:961 the accumulation 946:961 the accumulation of substitutions over time 946:988 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 1 25 theme recommended 208:218 arg1 strains 229:235 the recommended seasonal strains 204:235 the recommended seasonal strains 204:235 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 7 26 theme site 1421:1424 arg1 loss 1374:1377 the loss 1370:1377 the loss of the head domain N-linked glycosylation site 1370:1424 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 2 27 theme H3N2 427:430 arg1 strains 460:466 recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains 377:466 recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains 377:466 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 1 28 contain contain 158:164 arg1 vaccines 149:156 viral-based influenza vaccines 127:156 viral-based influenza vaccines 127:156 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 1 28 contain contain 158:164 arg2 antigens 190:197 neuraminidase (NA or N) antigens 166:197 neuraminidase (NA or N) antigens from the recommended seasonal strains 166:235 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 5 29 theme N1 911:912 arg1 antigenicity 914:925 N1 antigenicity 911:925 N1 antigenicity 911:925 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 7 30 link N-linked 1398:1405 arg1 site 1421:1424 the head domain N-linked glycosylation site 1382:1424 the head domain N-linked glycosylation site 1382:1424 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 2 31 theme NAs 368:370 arg1 antigenicity 352:363 the antigenicity 348:363 the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020 348:535 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 0 32 theme Antigenic 0:8 arg1 comparison 10:19 Antigenic comparison 0:19 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 0:116 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 35835790 6 33 theme similar 1149:1155 arg1 antigenicity 1157:1168 similar antigenicity 1149:1168 similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain 1149:1289 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 3 34 theme NA 639:640 arg1 activity 642:649 NA activity 639:649 NA activity in an enzyme-linked lectin assay 639:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 2 35 from antigenicity 352:363 arg1 viruses 472:478 viruses 472:478 viruses 472:478 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 2 35 from antigenicity 352:363 arg1 strains 460:466 recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains 377:466 recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains 377:466 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 5 36 theme site 1040:1043 arg1 loss 1006:1009 the loss 1002:1009 the loss of an N-linked glycosylation site (Asn386) in current N1s 1002:1067 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 36 theme site 1040:1043 arg1 accumulation 950:961 the accumulation 946:961 the accumulation of substitutions over time 946:988 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 37 theme substitutions 966:978 arg1 accumulation 950:961 the accumulation 946:961 the accumulation of substitutions over time 946:988 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 37 theme substitutions 966:978 arg1 loss 1006:1009 the loss 1002:1009 the loss of an N-linked glycosylation site (Asn386) in current N1s 1002:1067 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 4 38 theme circulating 716:726 arg1 viruses 733:739 circulating H1N1 viruses 716:739 circulating H1N1 viruses 716:739 Our results show that NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons are all antigenically similar and distinct from the NA in the H1N1 strain recommended for the 2010-2017 seasons. 35835790 3 39 link enzyme-linked 657:669 arg1 assay 678:682 an enzyme-linked lectin assay 654:682 an enzyme-linked lectin assay 654:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 6 40 theme vaccine 1276:1282 arg1 strain 1284:1289 the 2015-2016 vaccine strain 1262:1289 the 2015-2016 vaccine strain 1262:1289 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 2 41 from strains 460:466 arg1 NAs 368:370 NAs 368:370 NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020 368:535 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 2 41 from strains 460:466 arg1 antigenicity 352:363 the antigenicity 348:363 the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020 348:535 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 1 42 dep neuraminidase 166:178 arg1 N 187:187 N 187:187 N 187:187 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 1 42 dep neuraminidase 166:178 arg1 NA 181:182 NA 181:182 NA 181:182 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 6 43 theme 2015-2016 1266:1274 arg1 strain 1284:1289 the 2015-2016 vaccine strain 1262:1289 the 2015-2016 vaccine strain 1262:1289 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 0 44 from viruses 75:81 arg1 comparison 10:19 Antigenic comparison 0:19 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 0:116 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 35835790 7 45 theme recent 1320:1325 arg1 antigenicity 1330:1341 the recent N1 antigenicity 1316:1341 the recent N1 antigenicity 1316:1341 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 6 46 from viruses 1100:1106 arg1 NAs 1074:1076 The NAs 1070:1076 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains 1070:1140 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 2 47 theme H1N1 398:401 arg1 strains 460:466 recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains 377:466 recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains 377:466 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 0 48 theme neuraminidases 28:41 arg1 comparison 10:19 Antigenic comparison 0:19 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 0:116 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 35835790 7 49 gly glycosylation 1407:1419 arg2 site 1421:1424 the head domain N-linked glycosylation site 1382:1424 the head domain N-linked glycosylation site 1382:1424 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 2 50 from viruses 472:478 arg1 NAs 368:370 NAs 368:370 NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020 368:535 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 2 50 from viruses 472:478 arg1 antigenicity 352:363 the antigenicity 348:363 the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020 348:535 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 3 51 theme NA 582:583 arg1 titers 601:606 NA ferret antisera titers 582:606 NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay 582:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 1 52 theme seasonal 220:227 arg1 strains 229:235 the recommended seasonal strains 204:235 the recommended seasonal strains 204:235 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 0 53 theme influenza 55:63 arg1 viruses 75:81 recent influenza A vaccine viruses 48:81 recent influenza A vaccine viruses 48:81 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 35835790 3 54 theme 50 621:622 arg1 % 623:623 % 623:623 % 623:623 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 6 55 from N2 1256:1257 arg1 distinct 1238:1245 distinct 1238:1245 distinct 1238:1245 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 6 55 from N2 1256:1257 arg1 strain 1284:1289 the 2015-2016 vaccine strain 1262:1289 the 2015-2016 vaccine strain 1262:1289 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 0 56 theme recent 48:53 arg1 viruses 75:81 recent influenza A vaccine viruses 48:81 recent influenza A vaccine viruses 48:81 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 35835790 1 57 theme strain 304:309 arg1 process 321:327 the strain selection process 300:327 the strain selection process 300:327 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 4 58 theme H1N1 849:852 arg1 strain 854:859 the H1N1 strain 845:859 the H1N1 strain recommended for the 2010-2017 seasons 845:897 Our results show that NAs from circulating H1N1 viruses and vaccine strains for the 2017-2021 seasons are all antigenically similar and distinct from the NA in the H1N1 strain recommended for the 2010-2017 seasons. 35835790 3 59 theme activity 642:649 arg1 inhibition 625:634 50% inhibition 621:634 50% inhibition of NA activity in an enzyme-linked lectin assay 621:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 6 60 theme H3N2 1095:1098 arg1 viruses 1100:1106 circulating H3N2 viruses 1083:1106 circulating H3N2 viruses 1083:1106 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 1 61 theme viral-based 127:137 arg1 vaccines 149:156 viral-based influenza vaccines 127:156 viral-based influenza vaccines 127:156 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 3 62 from inhibition 625:634 arg1 assay 678:682 an enzyme-linked lectin assay 654:682 an enzyme-linked lectin assay 654:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 1 63 theme selection 311:319 arg1 process 321:327 the strain selection process 300:327 the strain selection process 300:327 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 1 64 from strains 229:235 arg1 antigens 190:197 neuraminidase (NA or N) antigens 166:197 neuraminidase (NA or N) antigens from the recommended seasonal strains 166:235 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 0 65 from strains 109:115 arg1 comparison 10:19 Antigenic comparison 0:19 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 0:116 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 35835790 7 66 theme N1 1327:1328 arg1 antigenicity 1330:1341 the recent N1 antigenicity 1316:1341 the recent N1 antigenicity 1316:1341 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 1 67 theme influenza 139:147 arg1 vaccines 149:156 viral-based influenza vaccines 127:156 viral-based influenza vaccines 127:156 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35835790 5 68 gly glycosylation 1026:1038 arg2 Asn386 1046:1051 Asn386 1046:1051 Asn386 1046:1051 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 68 gly glycosylation 1026:1038 arg2 site 1040:1043 an N-linked glycosylation site 1014:1043 an N-linked glycosylation site (Asn386) in current N1s 1014:1067 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 7 69 theme N2 1435:1436 arg1 antigenicity 1438:1449 N2 antigenicity 1435:1449 N2 antigenicity 1435:1449 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 5 70 from Changes 900:906 arg1 antigenicity 914:925 N1 antigenicity 911:925 N1 antigenicity 911:925 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 6 71 from strains 1134:1140 arg1 NAs 1074:1076 The NAs 1070:1076 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains 1070:1140 The NAs from circulating H3N2 viruses and the 2020-2021 vaccine strains showed similar antigenicity that varied across the N2s in the 2016-2020 vaccine strains and was distinct from the N2 in the 2015-2016 vaccine strain. 35835790 0 72 theme vaccine 67:73 arg1 viruses 75:81 recent influenza A vaccine viruses 48:81 recent influenza A vaccine viruses 48:81 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 35835790 2 73 theme recommended 386:396 arg1 H1N1 398:401 recently recommended H1N1 377:401 recently recommended H1N1 (2010-2021 seasons) 377:421 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 2 73 theme recommended 386:396 arg1 seasons 414:420 2010-2021 seasons 404:420 2010-2021 seasons 404:420 Here, we compared the antigenicity of NAs from recently recommended H1N1 (2010-2021 seasons) and H3N2 (2015-2021 seasons) vaccine strains and viruses that circulated between September 2019 and December 2020. 35835790 3 74 theme ferret 585:590 arg1 titers 601:606 NA ferret antisera titers 582:606 NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay 582:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 5 75 link N-linked 1017:1024 arg1 site 1040:1043 an N-linked glycosylation site 1014:1043 an N-linked glycosylation site (Asn386) in current N1s 1014:1067 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 5 75 link N-linked 1017:1024 arg1 Asn386 1046:1051 Asn386 1046:1051 Asn386 1046:1051 Changes in N1 antigenicity were attributed to the accumulation of substitutions over time, especially the loss of an N-linked glycosylation site (Asn386) in current N1s. 35835790 7 76 theme glycosylation 1407:1419 arg1 site 1421:1424 the head domain N-linked glycosylation site 1382:1424 the head domain N-linked glycosylation site 1382:1424 These data suggest that the recent N1 antigenicity has remained similar since the loss of the head domain N-linked glycosylation site, whereas N2 antigenicity has changed more incrementally each season. 35835790 0 77 theme A 65:65 arg1 viruses 75:81 recent influenza A vaccine viruses 48:81 recent influenza A vaccine viruses 48:81 Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019-2020 circulating strains. 35835790 3 78 theme lectin 671:676 arg1 assay 678:682 an enzyme-linked lectin assay 654:682 an enzyme-linked lectin assay 654:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 3 79 theme antisera 592:599 arg1 titers 601:606 NA ferret antisera titers 582:606 NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay 582:682 The antigenicity was evaluated by measuring NA ferret antisera titers that provide 50% inhibition of NA activity in an enzyme-linked lectin assay. 35835790 1 80 theme neuraminidase 166:178 arg1 antigens 190:197 neuraminidase (NA or N) antigens 166:197 neuraminidase (NA or N) antigens from the recommended seasonal strains 166:235 Although viral-based influenza vaccines contain neuraminidase (NA or N) antigens from the recommended seasonal strains, NA is not extensively evaluated like hemagglutinin (H) during the strain selection process. 35684346 4 0 from butyl-4-aminobenzoate 667:687 arg1 glutamicum 724:733 C. glutamicum 721:733 C. glutamicum 721:733 In this study, we successfully and efficiently glycosylated therapeutic butyl-4-aminobenzoate and other N-linked compounds in C. glutamicum using a promiscuous YdhE, which is a glycosyltransferase from Bacillus lichenformis. 35684346 6 1 theme glycosylated 1069:1080 arg1 products 1082:1089 the glycosylated products 1065:1089 the glycosylated products 1065:1089 With glucose as the sole carbon source, we achieved a conversion rate of almost 96% of the glycosylated products in the culture medium. 35684346 6 2 gly glycosylated 1069:1080 arg1 products 1082:1089 the glycosylated products 1065:1089 the glycosylated products 1065:1089 With glucose as the sole carbon source, we achieved a conversion rate of almost 96% of the glycosylated products in the culture medium. 35684346 1 3 theme high 175:178 arg1 ability 180:186 its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory 171:271 its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory 171:271 Corynebacterium glutamicum is traditionally known as a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory. 35684346 6 4 theme sole 998:1001 arg1 source 1010:1015 the sole carbon source 994:1015 the sole carbon source 994:1015 With glucose as the sole carbon source, we achieved a conversion rate of almost 96% of the glycosylated products in the culture medium. 35684346 7 5 theme simple 1192:1197 arg1 method 1212:1217 a simple purification method 1190:1217 a simple purification method 1190:1217 The glycosylated product of high concentration was successfully purified by a simple purification method, and subjected to further analysis. 35684346 3 6 theme compounds 541:549 arg1 activities 520:529 the activities 516:529 the activities of useful compounds 516:549 One of the well-studied ways to improve the activities of useful compounds is glucosylation with glycosyltransferases. 35684346 6 7 theme % 1060:1060 arg1 rate 1043:1046 a conversion rate 1030:1046 a conversion rate of almost 96% of the glycosylated products in the culture medium 1030:1111 With glucose as the sole carbon source, we achieved a conversion rate of almost 96% of the glycosylated products in the culture medium. 35684346 3 8 theme well-studied 487:498 arg1 ways 500:503 the well-studied ways 483:503 the well-studied ways 483:503 One of the well-studied ways to improve the activities of useful compounds is glucosylation with glycosyltransferases. 35684346 0 9 from N-Glucosylation 0:14 arg1 glutamicum 35:44 Corynebacterium glutamicum 19:44 Corynebacterium glutamicum with YdhE from Bacillus lichenformis 19:81 N-Glucosylation in Corynebacterium glutamicum with YdhE from Bacillus lichenformis. 35684346 3 10 with glucosylation 554:566 arg1 glycosyltransferases 573:592 glycosyltransferases 573:592 glycosyltransferases 573:592 One of the well-studied ways to improve the activities of useful compounds is glucosylation with glycosyltransferases. 35684346 3 11 theme useful 534:539 arg1 compounds 541:549 useful compounds 534:549 useful compounds 534:549 One of the well-studied ways to improve the activities of useful compounds is glucosylation with glycosyltransferases. 35684346 8 12 theme N-linked 1320:1327 arg1 compounds 1329:1337 N-linked compounds 1320:1337 N-linked compounds 1320:1337 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 4 13 theme N-linked 699:706 arg1 compounds 708:716 other N-linked compounds 693:716 other N-linked compounds 693:716 In this study, we successfully and efficiently glycosylated therapeutic butyl-4-aminobenzoate and other N-linked compounds in C. glutamicum using a promiscuous YdhE, which is a glycosyltransferase from Bacillus lichenformis. 35684346 1 14 theme Corynebacterium 84:98 arg1 microorganism 150:162 a food-grade microorganism 137:162 a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory 137:271 Corynebacterium glutamicum is traditionally known as a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory. 35684346 1 14 theme Corynebacterium 84:98 arg1 glutamicum 100:109 Corynebacterium glutamicum 84:109 Corynebacterium glutamicum 84:109 Corynebacterium glutamicum is traditionally known as a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory. 35684346 4 15 theme promiscuous 743:753 arg1 glycosyltransferase 772:790 a glycosyltransferase 770:790 a glycosyltransferase from Bacillus lichenformis 770:817 In this study, we successfully and efficiently glycosylated therapeutic butyl-4-aminobenzoate and other N-linked compounds in C. glutamicum using a promiscuous YdhE, which is a glycosyltransferase from Bacillus lichenformis. 35684346 4 15 theme promiscuous 743:753 arg1 YdhE 755:758 a promiscuous YdhE 741:758 a promiscuous YdhE 741:758 In this study, we successfully and efficiently glycosylated therapeutic butyl-4-aminobenzoate and other N-linked compounds in C. glutamicum using a promiscuous YdhE, which is a glycosyltransferase from Bacillus lichenformis. 35684346 2 16 theme advantageous 428:439 arg1 system 468:473 the therapeutically advantageous C. glutamicum cell factory system 408:473 the therapeutically advantageous C. glutamicum cell factory system 408:473 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 5 17 theme efficient 824:832 arg1 glucosylation 834:846 efficient glucosylation 824:846 efficient glucosylation 824:846 For efficient glucosylation, components, such as promoter, codons sequence, expression temperatures, and substrate and glucose concentrations were optimized. 35684346 4 18 theme therapeutic 655:665 arg1 butyl-4-aminobenzoate 667:687 therapeutic butyl-4-aminobenzoate 655:687 therapeutic butyl-4-aminobenzoate 655:687 In this study, we successfully and efficiently glycosylated therapeutic butyl-4-aminobenzoate and other N-linked compounds in C. glutamicum using a promiscuous YdhE, which is a glycosyltransferase from Bacillus lichenformis. 35684346 8 19 theme compounds 1329:1337 arg1 glucosylation 1303:1315 glucosylation 1303:1315 glucosylation of N-linked compounds in C. glutamicum 1303:1354 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 8 19 theme compounds 1329:1337 arg1 This 1255:1258 This 1255:1258 This 1255:1258 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 8 19 theme compounds 1329:1337 arg1 report 1265:1270 a report 1263:1270 a report of the in vivo cultivation 1263:1297 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 5 20 theme glucose 939:945 arg1 concentrations 947:960 glucose concentrations 939:960 glucose concentrations 939:960 For efficient glucosylation, components, such as promoter, codons sequence, expression temperatures, and substrate and glucose concentrations were optimized. 35684346 5 21 theme codons 879:884 arg1 sequence 886:893 codons sequence 879:893 codons sequence 879:893 For efficient glucosylation, components, such as promoter, codons sequence, expression temperatures, and substrate and glucose concentrations were optimized. 35684346 8 22 from report 1265:1270 arg1 glutamicum 1345:1354 C. glutamicum 1342:1354 C. glutamicum 1342:1354 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 7 23 theme high 1142:1145 arg1 concentration 1147:1159 high concentration 1142:1159 high concentration 1142:1159 The glycosylated product of high concentration was successfully purified by a simple purification method, and subjected to further analysis. 35684346 2 24 theme therapeutics 335:346 arg1 activities 314:323 the activities 310:323 the activities of useful therapeutics and pharmaceutical compounds 310:375 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 7 25 theme further 1237:1243 arg1 analysis 1245:1252 further analysis 1237:1252 further analysis 1237:1252 The glycosylated product of high concentration was successfully purified by a simple purification method, and subjected to further analysis. 35684346 1 26 theme amino 199:203 arg1 acids 205:209 amino acids 199:209 amino acids 199:209 Corynebacterium glutamicum is traditionally known as a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory. 35684346 7 27 theme concentration 1147:1159 arg1 product 1131:1137 The glycosylated product 1114:1137 The glycosylated product of high concentration 1114:1159 The glycosylated product of high concentration was successfully purified by a simple purification method, and subjected to further analysis. 35684346 8 28 from glucosylation 1303:1315 arg1 glutamicum 1345:1354 C. glutamicum 1342:1354 C. glutamicum 1342:1354 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 2 29 theme useful 328:333 arg1 therapeutics 335:346 useful therapeutics 328:346 useful therapeutics 328:346 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 8 30 dep in 1279:1280 arg1 vivo 1282:1285 vivo 1282:1285 vivo 1282:1285 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 4 31 from lichenformis 806:817 arg1 glycosyltransferase 772:790 a glycosyltransferase 770:790 a glycosyltransferase from Bacillus lichenformis 770:817 In this study, we successfully and efficiently glycosylated therapeutic butyl-4-aminobenzoate and other N-linked compounds in C. glutamicum using a promiscuous YdhE, which is a glycosyltransferase from Bacillus lichenformis. 35684346 4 31 from lichenformis 806:817 arg1 YdhE 755:758 a promiscuous YdhE 741:758 a promiscuous YdhE 741:758 In this study, we successfully and efficiently glycosylated therapeutic butyl-4-aminobenzoate and other N-linked compounds in C. glutamicum using a promiscuous YdhE, which is a glycosyltransferase from Bacillus lichenformis. 35684346 2 32 theme factory 460:466 arg1 system 468:473 the therapeutically advantageous C. glutamicum cell factory system 408:473 the therapeutically advantageous C. glutamicum cell factory system 408:473 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 2 33 theme system 468:473 arg1 engineering 393:403 the engineering 389:403 the engineering of the therapeutically advantageous C. glutamicum cell factory system 389:473 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 6 34 theme conversion 1032:1041 arg1 rate 1043:1046 a conversion rate 1030:1046 a conversion rate of almost 96% of the glycosylated products in the culture medium 1030:1111 With glucose as the sole carbon source, we achieved a conversion rate of almost 96% of the glycosylated products in the culture medium. 35684346 7 35 gly glycosylated 1118:1129 arg1 product 1131:1137 The glycosylated product 1114:1137 The glycosylated product of high concentration 1114:1159 The glycosylated product of high concentration was successfully purified by a simple purification method, and subjected to further analysis. 35684346 4 36 from compounds 708:716 arg1 glutamicum 724:733 C. glutamicum 721:733 C. glutamicum 721:733 In this study, we successfully and efficiently glycosylated therapeutic butyl-4-aminobenzoate and other N-linked compounds in C. glutamicum using a promiscuous YdhE, which is a glycosyltransferase from Bacillus lichenformis. 35684346 2 37 theme cell 455:458 arg1 system 468:473 the therapeutically advantageous C. glutamicum cell factory system 408:473 the therapeutically advantageous C. glutamicum cell factory system 408:473 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 2 38 theme compounds 367:375 arg1 activities 314:323 the activities 310:323 the activities of useful therapeutics and pharmaceutical compounds 310:375 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 6 39 theme culture 1098:1104 arg1 medium 1106:1111 the culture medium 1094:1111 the culture medium 1094:1111 With glucose as the sole carbon source, we achieved a conversion rate of almost 96% of the glycosylated products in the culture medium. 35684346 1 40 theme endotoxin-free 219:232 arg1 factory 265:271 its endotoxin-free recombinant protein expression factory 215:271 its endotoxin-free recombinant protein expression factory 215:271 Corynebacterium glutamicum is traditionally known as a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory. 35684346 8 41 theme cultivation 1287:1297 arg1 glucosylation 1303:1315 glucosylation 1303:1315 glucosylation of N-linked compounds in C. glutamicum 1303:1354 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 8 41 theme cultivation 1287:1297 arg1 This 1255:1258 This 1255:1258 This 1255:1258 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 8 41 theme cultivation 1287:1297 arg1 report 1265:1270 a report 1263:1270 a report of the in vivo cultivation 1263:1297 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 6 42 from rate 1043:1046 arg1 medium 1106:1111 the culture medium 1094:1111 the culture medium 1094:1111 With glucose as the sole carbon source, we achieved a conversion rate of almost 96% of the glycosylated products in the culture medium. 35684346 2 43 dep C. 441:442 arg1 glutamicum 444:453 glutamicum 444:453 glutamicum 444:453 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 0 44 with glutamicum 35:44 arg1 YdhE 51:54 YdhE 51:54 YdhE 51:54 N-Glucosylation in Corynebacterium glutamicum with YdhE from Bacillus lichenformis. 35684346 2 45 theme C. 441:442 arg1 system 468:473 the therapeutically advantageous C. glutamicum cell factory system 408:473 the therapeutically advantageous C. glutamicum cell factory system 408:473 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 7 46 theme purification 1199:1210 arg1 method 1212:1217 a simple purification method 1190:1217 a simple purification method 1190:1217 The glycosylated product of high concentration was successfully purified by a simple purification method, and subjected to further analysis. 35684346 0 47 from lichenformis 70:81 arg1 glutamicum 35:44 Corynebacterium glutamicum 19:44 Corynebacterium glutamicum with YdhE from Bacillus lichenformis 19:81 N-Glucosylation in Corynebacterium glutamicum with YdhE from Bacillus lichenformis. 35684346 7 48 theme glycosylated 1118:1129 arg1 product 1131:1137 The glycosylated product 1114:1137 The glycosylated product of high concentration 1114:1159 The glycosylated product of high concentration was successfully purified by a simple purification method, and subjected to further analysis. 35684346 6 49 theme carbon 1003:1008 arg1 source 1010:1015 the sole carbon source 994:1015 the sole carbon source 994:1015 With glucose as the sole carbon source, we achieved a conversion rate of almost 96% of the glycosylated products in the culture medium. 35684346 1 50 theme food-grade 139:148 arg1 microorganism 150:162 a food-grade microorganism 137:162 a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory 137:271 Corynebacterium glutamicum is traditionally known as a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory. 35684346 1 50 theme food-grade 139:148 arg1 glutamicum 100:109 Corynebacterium glutamicum 84:109 Corynebacterium glutamicum 84:109 Corynebacterium glutamicum is traditionally known as a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory. 35684346 4 51 link N-linked 699:706 arg1 compounds 708:716 other N-linked compounds 693:716 other N-linked compounds 693:716 In this study, we successfully and efficiently glycosylated therapeutic butyl-4-aminobenzoate and other N-linked compounds in C. glutamicum using a promiscuous YdhE, which is a glycosyltransferase from Bacillus lichenformis. 35684346 6 52 theme products 1082:1089 arg1 % 1060:1060 almost 96% 1051:1060 almost 96% of the glycosylated products 1051:1089 With glucose as the sole carbon source, we achieved a conversion rate of almost 96% of the glycosylated products in the culture medium. 35684346 6 52 theme products 1082:1089 arg1 products 1082:1089 the glycosylated products 1065:1089 the glycosylated products 1065:1089 With glucose as the sole carbon source, we achieved a conversion rate of almost 96% of the glycosylated products in the culture medium. 35684346 2 53 theme pharmaceutical 352:365 arg1 compounds 367:375 pharmaceutical compounds 352:375 pharmaceutical compounds 352:375 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 1 54 theme protein 246:252 arg1 factory 265:271 its endotoxin-free recombinant protein expression factory 215:271 its endotoxin-free recombinant protein expression factory 215:271 Corynebacterium glutamicum is traditionally known as a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory. 35684346 8 55 link N-linked 1320:1327 arg1 compounds 1329:1337 N-linked compounds 1320:1337 N-linked compounds 1320:1337 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 5 56 theme expression 896:905 arg1 temperatures 907:918 expression temperatures 896:918 expression temperatures 896:918 For efficient glucosylation, components, such as promoter, codons sequence, expression temperatures, and substrate and glucose concentrations were optimized. 35684346 1 57 theme expression 254:263 arg1 factory 265:271 its endotoxin-free recombinant protein expression factory 215:271 its endotoxin-free recombinant protein expression factory 215:271 Corynebacterium glutamicum is traditionally known as a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory. 35684346 1 58 theme recombinant 234:244 arg1 factory 265:271 its endotoxin-free recombinant protein expression factory 215:271 its endotoxin-free recombinant protein expression factory 215:271 Corynebacterium glutamicum is traditionally known as a food-grade microorganism due to its high ability to produce amino acids and its endotoxin-free recombinant protein expression factory. 35684346 2 59 theme recent 277:282 arg1 years 284:288 recent years 277:288 recent years 277:288 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35684346 3 60 theme ways 500:503 arg1 One 476:478 One 476:478 One 476:478 One of the well-studied ways to improve the activities of useful compounds is glucosylation with glycosyltransferases. 35684346 3 60 theme ways 500:503 arg1 ways 500:503 the well-studied ways 483:503 the well-studied ways 483:503 One of the well-studied ways to improve the activities of useful compounds is glucosylation with glycosyltransferases. 35684346 4 61 theme other 693:697 arg1 compounds 708:716 other N-linked compounds 693:716 other N-linked compounds 693:716 In this study, we successfully and efficiently glycosylated therapeutic butyl-4-aminobenzoate and other N-linked compounds in C. glutamicum using a promiscuous YdhE, which is a glycosyltransferase from Bacillus lichenformis. 35684346 8 62 theme in 1279:1280 arg1 cultivation 1287:1297 the in vivo cultivation 1275:1297 the in vivo cultivation 1275:1297 This is a report of the in vivo cultivation and glucosylation of N-linked compounds in C. glutamicum. 35684346 0 63 from glutamicum 35:44 arg1 N-Glucosylation 0:14 N-Glucosylation 0:14 N-Glucosylation 0:14 N-Glucosylation in Corynebacterium glutamicum with YdhE from Bacillus lichenformis. 35684346 0 64 theme Corynebacterium 19:33 arg1 glutamicum 35:44 Corynebacterium glutamicum 19:44 Corynebacterium glutamicum with YdhE from Bacillus lichenformis 19:81 N-Glucosylation in Corynebacterium glutamicum with YdhE from Bacillus lichenformis. 35684346 2 65 dep studies 291:297 arg1 improve 302:308 improve 302:308 to improve the activities of useful therapeutics and pharmaceutical compounds 299:375 In recent years, studies to improve the activities of useful therapeutics and pharmaceutical compounds have led to the engineering of the therapeutically advantageous C. glutamicum cell factory system. 35573732 0 0 theme Lysosome-Associated 108:126 arg1 Protein-2 137:145 Glycosylated Lysosome-Associated Membrane Protein-2 95:145 Glycosylated Lysosome-Associated Membrane Protein-2 95:145 Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2. 35573732 4 1 theme nascent 553:559 arg1 method 571:576 a nascent proteomic method 551:576 a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line 551:655 Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. 35573732 8 2 theme autophagy 1113:1121 arg1 inhibition 1055:1064 the inhibition 1051:1064 the inhibition of Cathepsin D maturation 1051:1090 NGI-1 treatment also led to the inhibition of Cathepsin D maturation and the induction of autophagy. 35573732 8 2 theme autophagy 1113:1121 arg1 induction 1100:1108 the induction 1096:1108 the induction of autophagy 1096:1121 NGI-1 treatment also led to the inhibition of Cathepsin D maturation and the induction of autophagy. 35573732 6 3 theme Glycoproteomic 778:791 arg1 analysis 793:800 Glycoproteomic analysis 778:800 Glycoproteomic analysis 778:800 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 7 4 theme site-specific 955:967 arg1 N-glycopeptides 976:990 LAMP2 site-specific intact N-glycopeptides 949:990 LAMP2 site-specific intact N-glycopeptides 949:990 Moreover, the alterations of LAMP2 site-specific intact N-glycopeptides were comprehensively assessed. 35573732 6 5 gly glycopeptides 828:840 arg1 NICA 854:857 NICA 854:857 NICA 854:857 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 6 5 gly glycopeptides 828:840 arg1 CEIP2 864:868 CEIP2 864:868 CEIP2 864:868 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 6 5 gly glycopeptides 828:840 arg1 LAMP2 847:851 LAMP2 847:851 LAMP2 847:851 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 6 5 gly glycopeptides 828:840 arg2 glycopeptides 828:840 glycopeptides 828:840 glycopeptides from LAMP2, NICA, and CEIP2 828:868 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 0 6 theme Glycosylated 95:106 arg1 Protein-2 137:145 Glycosylated Lysosome-Associated Membrane Protein-2 95:145 Glycosylated Lysosome-Associated Membrane Protein-2 95:145 Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2. 35573732 1 7 contain has 173:175 arg1 inhibition 162:171 Glycosylation inhibition 148:171 Glycosylation inhibition 148:171 Glycosylation inhibition has great potential in cancer treatment. 35573732 1 7 contain has 173:175 arg2 potential 183:191 great potential 177:191 great potential 177:191 Glycosylation inhibition has great potential in cancer treatment. 35573732 3 8 gly glycosylation 481:493 arg1 cells 508:512 mammalian cells 498:512 mammalian cells 498:512 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 0 9 theme Protein-2 137:145 arg1 Expression 81:90 Expression 81:90 Expression of Glycosylated Lysosome-Associated Membrane Protein-2 81:145 Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2. 35573732 9 10 theme autophagy 1272:1280 arg1 occurrence 1236:1245 the occurrence 1232:1245 the occurrence of lysosomal defects and autophagy 1232:1280 In summary, we provided evidence that NGI-1 repressed the expression of glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy. 35573732 9 11 theme defects 1260:1266 arg1 occurrence 1236:1245 the occurrence 1232:1245 the occurrence of lysosomal defects and autophagy 1232:1280 In summary, we provided evidence that NGI-1 repressed the expression of glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy. 35573732 4 12 theme cell 647:650 arg1 line 652:655 hepatocellular carcinoma (HCC) cell line 616:655 hepatocellular carcinoma (HCC) cell line 616:655 Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. 35573732 0 13 theme Membrane 128:135 arg1 Protein-2 137:145 Glycosylated Lysosome-Associated Membrane Protein-2 95:145 Glycosylated Lysosome-Associated Membrane Protein-2 95:145 Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2. 35573732 6 14 from NICA 854:857 arg1 glycopeptides 828:840 glycopeptides 828:840 glycopeptides from LAMP2, NICA, and CEIP2 828:868 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 6 14 from NICA 854:857 arg1 abundance 815:823 the abundance 811:823 the abundance of glycopeptides from LAMP2, NICA, and CEIP2 811:868 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 8 15 theme D 1079:1079 arg1 maturation 1081:1090 Cathepsin D maturation 1069:1090 Cathepsin D maturation 1069:1090 NGI-1 treatment also led to the inhibition of Cathepsin D maturation and the induction of autophagy. 35573732 5 16 theme hydrophilic 667:677 arg1 HILIC 714:718 HILIC 714:718 HILIC 714:718 Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. 35573732 5 16 theme hydrophilic 667:677 arg1 chromatography 698:711 hydrophilic interaction liquid chromatography 667:711 hydrophilic interaction liquid chromatography (HILIC) 667:719 Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. 35573732 8 17 theme Cathepsin 1069:1077 arg1 maturation 1081:1090 Cathepsin D maturation 1069:1090 Cathepsin D maturation 1069:1090 NGI-1 treatment also led to the inhibition of Cathepsin D maturation and the induction of autophagy. 35573732 4 18 from effect 597:602 arg1 line 652:655 hepatocellular carcinoma (HCC) cell line 616:655 hepatocellular carcinoma (HCC) cell line 616:655 Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. 35573732 5 19 theme interaction 679:689 arg1 HILIC 714:718 HILIC 714:718 HILIC 714:718 Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. 35573732 5 19 theme interaction 679:689 arg1 chromatography 698:711 hydrophilic interaction liquid chromatography 667:711 hydrophilic interaction liquid chromatography (HILIC) 667:719 Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. 35573732 3 20 theme great 454:458 arg1 approach 460:467 a great approach 452:467 a great approach to regulate glycosylation in mammalian cells 452:512 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 3 21 theme N-linked 398:405 arg1 NGI-1 434:438 NGI-1 434:438 NGI-1 434:438 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 3 21 theme N-linked 398:405 arg1 inhibitor-1 421:431 N-linked glycosylation inhibitor-1 398:431 N-linked glycosylation inhibitor-1 (NGI-1) 398:439 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 5 22 theme liquid 691:696 arg1 HILIC 714:718 HILIC 714:718 HILIC 714:718 Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. 35573732 5 22 theme liquid 691:696 arg1 chromatography 698:711 hydrophilic interaction liquid chromatography 667:711 hydrophilic interaction liquid chromatography (HILIC) 667:719 Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. 35573732 8 23 theme maturation 1081:1090 arg1 inhibition 1055:1064 the inhibition 1051:1064 the inhibition of Cathepsin D maturation 1051:1090 NGI-1 treatment also led to the inhibition of Cathepsin D maturation and the induction of autophagy. 35573732 8 23 theme maturation 1081:1090 arg1 induction 1100:1108 the induction 1096:1108 the induction of autophagy 1096:1121 NGI-1 treatment also led to the inhibition of Cathepsin D maturation and the induction of autophagy. 35573732 3 24 theme mammalian 498:506 arg1 cells 508:512 mammalian cells 498:512 mammalian cells 498:512 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 0 25 theme Nascent 0:6 arg1 Glycoproteome 8:20 Nascent Glycoproteome 0:20 Nascent Glycoproteome 0:20 Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2. 35573732 3 26 link N-linked 398:405 arg1 NGI-1 434:438 NGI-1 434:438 NGI-1 434:438 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 3 26 link N-linked 398:405 arg1 inhibitor-1 421:431 N-linked glycosylation inhibitor-1 398:431 N-linked glycosylation inhibitor-1 (NGI-1) 398:439 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 4 27 theme NGI-1 607:611 arg1 effect 597:602 the effect 593:602 the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line 593:655 Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. 35573732 3 28 theme small-molecule 341:354 arg1 inhibitor 356:364 a cell-permeable small-molecule inhibitor 324:364 a cell-permeable small-molecule inhibitor with reduced cellular toxicity 324:395 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 4 29 theme carcinoma 631:639 arg1 line 652:655 hepatocellular carcinoma (HCC) cell line 616:655 hepatocellular carcinoma (HCC) cell line 616:655 Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. 35573732 5 30 theme glycosylated 755:766 arg1 peptides 768:775 glycosylated peptides 755:775 glycosylated peptides 755:775 Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. 35573732 2 31 theme corresponding 227:239 arg1 response 250:257 the corresponding cellular response 223:257 the corresponding cellular response 223:257 However, the corresponding cellular response, protein expression and glycosylation changes remain unclear. 35573732 1 32 theme Glycosylation 148:160 arg1 inhibition 162:171 Glycosylation inhibition 148:171 Glycosylation inhibition 148:171 Glycosylation inhibition has great potential in cancer treatment. 35573732 6 33 from LAMP2 847:851 arg1 glycopeptides 828:840 glycopeptides 828:840 glycopeptides from LAMP2, NICA, and CEIP2 828:868 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 6 33 from LAMP2 847:851 arg1 abundance 815:823 the abundance 811:823 the abundance of glycopeptides from LAMP2, NICA, and CEIP2 811:868 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 0 34 theme Glycosylation 44:56 arg1 Inhibitor-1 58:68 N-Linked Glycosylation Inhibitor-1 35:68 N-Linked Glycosylation Inhibitor-1 35:68 Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2. 35573732 4 35 theme hepatocellular 616:629 arg1 HCC 642:644 HCC 642:644 HCC 642:644 Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. 35573732 4 35 theme hepatocellular 616:629 arg1 carcinoma 631:639 hepatocellular carcinoma 616:639 hepatocellular carcinoma (HCC) cell line 616:655 Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. 35573732 5 36 theme peptides 768:775 arg1 enrichment 741:750 the enrichment 737:750 the enrichment of glycosylated peptides 737:775 Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. 35573732 9 37 theme glycosylated 1196:1207 arg1 LAMP2 1209:1213 glycosylated LAMP2 1196:1213 glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy 1196:1280 In summary, we provided evidence that NGI-1 repressed the expression of glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy. 35573732 0 38 theme N-Linked 35:42 arg1 Inhibitor-1 58:68 N-Linked Glycosylation Inhibitor-1 35:68 N-Linked Glycosylation Inhibitor-1 35:68 Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2. 35573732 3 39 theme cell-permeable 326:339 arg1 inhibitor 356:364 a cell-permeable small-molecule inhibitor 324:364 a cell-permeable small-molecule inhibitor with reduced cellular toxicity 324:395 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 2 40 theme glycosylation 283:295 arg1 changes 297:303 glycosylation changes 283:303 glycosylation changes 283:303 However, the corresponding cellular response, protein expression and glycosylation changes remain unclear. 35573732 9 41 theme LAMP2 1209:1213 arg1 expression 1182:1191 the expression 1178:1191 the expression of glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy 1178:1280 In summary, we provided evidence that NGI-1 repressed the expression of glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy. 35573732 3 42 with inhibitor 356:364 arg1 toxicity 388:395 reduced cellular toxicity 371:395 reduced cellular toxicity 371:395 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 3 43 theme cellular 379:386 arg1 toxicity 388:395 reduced cellular toxicity 371:395 reduced cellular toxicity 371:395 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 4 44 theme first 528:532 arg1 time 534:537 the first time 524:537 the first time 524:537 Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. 35573732 6 45 theme glycopeptides 828:840 arg1 abundance 815:823 the abundance 811:823 the abundance of glycopeptides from LAMP2, NICA, and CEIP2 811:868 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 5 46 gly glycosylated 755:766 arg1 peptides 768:775 glycosylated peptides 755:775 glycosylated peptides 755:775 Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. 35573732 2 47 theme protein 260:266 arg1 expression 268:277 protein expression 260:277 protein expression 260:277 However, the corresponding cellular response, protein expression and glycosylation changes remain unclear. 35573732 6 48 from CEIP2 864:868 arg1 glycopeptides 828:840 glycopeptides 828:840 glycopeptides from LAMP2, NICA, and CEIP2 828:868 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 6 48 from CEIP2 864:868 arg1 abundance 815:823 the abundance 811:823 the abundance of glycopeptides from LAMP2, NICA, and CEIP2 811:868 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 6 49 from abundance 815:823 arg1 NICA 854:857 NICA 854:857 NICA 854:857 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 6 49 from abundance 815:823 arg1 CEIP2 864:868 CEIP2 864:868 CEIP2 864:868 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 6 49 from abundance 815:823 arg1 LAMP2 847:851 LAMP2 847:851 LAMP2 847:851 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 9 50 gly glycosylated 1196:1207 arg1 LAMP2 1209:1213 glycosylated LAMP2 1196:1213 glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy 1196:1280 In summary, we provided evidence that NGI-1 repressed the expression of glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy. 35573732 6 51 theme NGI-1 903:907 arg1 treatment 909:917 NGI-1 treatment 903:917 NGI-1 treatment 903:917 Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. 35573732 8 52 theme NGI-1 1023:1027 arg1 treatment 1029:1037 NGI-1 treatment 1023:1037 NGI-1 treatment 1023:1037 NGI-1 treatment also led to the inhibition of Cathepsin D maturation and the induction of autophagy. 35573732 1 53 theme great 177:181 arg1 potential 183:191 great potential 177:191 great potential 177:191 Glycosylation inhibition has great potential in cancer treatment. 35573732 3 54 from glycosylation 481:493 arg1 cells 508:512 mammalian cells 498:512 mammalian cells 498:512 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 3 55 theme reduced 371:377 arg1 toxicity 388:395 reduced cellular toxicity 371:395 reduced cellular toxicity 371:395 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 7 56 gly N-glycopeptides 976:990 arg2 N-glycopeptides 976:990 LAMP2 site-specific intact N-glycopeptides 949:990 LAMP2 site-specific intact N-glycopeptides 949:990 Moreover, the alterations of LAMP2 site-specific intact N-glycopeptides were comprehensively assessed. 35573732 7 57 theme intact 969:974 arg1 N-glycopeptides 976:990 LAMP2 site-specific intact N-glycopeptides 949:990 LAMP2 site-specific intact N-glycopeptides 949:990 Moreover, the alterations of LAMP2 site-specific intact N-glycopeptides were comprehensively assessed. 35573732 3 58 theme glycosylation 407:419 arg1 NGI-1 434:438 NGI-1 434:438 NGI-1 434:438 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 3 58 theme glycosylation 407:419 arg1 inhibitor-1 421:431 N-linked glycosylation inhibitor-1 398:431 N-linked glycosylation inhibitor-1 (NGI-1) 398:439 As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. 35573732 2 59 theme cellular 241:248 arg1 response 250:257 the corresponding cellular response 223:257 the corresponding cellular response 223:257 However, the corresponding cellular response, protein expression and glycosylation changes remain unclear. 35573732 7 60 theme N-glycopeptides 976:990 arg1 alterations 934:944 the alterations 930:944 the alterations of LAMP2 site-specific intact N-glycopeptides 930:990 Moreover, the alterations of LAMP2 site-specific intact N-glycopeptides were comprehensively assessed. 35573732 4 61 theme proteomic 561:569 arg1 method 571:576 a nascent proteomic method 551:576 a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line 551:655 Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. 35573732 9 62 theme lysosomal 1250:1258 arg1 defects 1260:1266 lysosomal defects 1250:1266 lysosomal defects 1250:1266 In summary, we provided evidence that NGI-1 repressed the expression of glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy. 35573732 1 63 theme cancer 196:201 arg1 treatment 203:211 cancer treatment 196:211 cancer treatment 196:211 Glycosylation inhibition has great potential in cancer treatment. 35573732 7 64 theme LAMP2 949:953 arg1 N-glycopeptides 976:990 LAMP2 site-specific intact N-glycopeptides 949:990 LAMP2 site-specific intact N-glycopeptides 949:990 Moreover, the alterations of LAMP2 site-specific intact N-glycopeptides were comprehensively assessed. 36847543 7 0 with coexistence 1172:1182 arg1 coli 1192:1195 E. coli 1189:1195 E. coli 1189:1195 Finally, we analyzed the transcriptomic profile of E. faecalis in response to coexistence with E. coli and S. enteritidis in the triple-species biofilm. 36847543 7 0 with coexistence 1172:1182 arg1 enteritidis 1204:1214 S. enteritidis 1201:1214 S. enteritidis 1201:1214 Finally, we analyzed the transcriptomic profile of E. faecalis in response to coexistence with E. coli and S. enteritidis in the triple-species biofilm. 36847543 10 1 theme IMPORTANCE 1844:1853 arg1 biofilms 1865:1872 IMPORTANCE Bacterial biofilms 1844:1872 IMPORTANCE Bacterial biofilms 1844:1872 IMPORTANCE Bacterial biofilms possess distinct community properties that affect various aspects of our daily lives. 36847543 15 2 theme triple-species 2696:2709 arg1 biofilms 2711:2718 triple-species biofilms 2696:2718 triple-species biofilms 2696:2718 In combination with transcriptomic analyses, this pilot study explores the potential underlying mechanisms that lead to the dominance of E. faecalis in triple-species biofilms. 36847543 9 3 theme interspecies 1764:1775 arg1 interactions 1777:1788 interspecies interactions 1764:1788 interspecies interactions 1764:1788 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 13 4 from effects 2284:2290 arg1 development 2317:2327 development 2317:2327 development 2317:2327 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 13 4 from effects 2284:2290 arg1 survival 2333:2340 survival 2333:2340 survival 2333:2340 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 11 5 theme chemical 2015:2022 arg1 disinfectants 2024:2036 chemical disinfectants 2015:2036 chemical disinfectants 2015:2036 In particular, biofilms exhibit increased tolerance to chemical disinfectants, antimicrobial agents, and host immune responses. 36847543 6 6 theme extracellular 939:951 arg1 ECM 961:963 ECM 961:963 ECM 961:963 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 6 6 theme extracellular 939:951 arg1 matrix 953:958 extracellular matrix 939:958 the extracellular matrix (ECM) composition of the triple-species biofilm 935:1006 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 10 7 theme distinct 1882:1889 arg1 properties 1901:1910 distinct community properties 1882:1910 distinct community properties that affect various aspects of our daily lives 1882:1957 IMPORTANCE Bacterial biofilms possess distinct community properties that affect various aspects of our daily lives. 36847543 9 8 theme clinical 1798:1805 arg1 treatment 1807:1815 the clinical treatment 1794:1815 the clinical treatment of polymicrobial biofilms 1794:1841 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 14 9 theme triple-species 2490:2503 arg1 formation 2513:2521 triple-species biofilm formation 2490:2521 triple-species biofilm formation with a static model 2490:2541 Here, we address the effects of the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis on triple-species biofilm formation with a static model. 36847543 12 10 theme biofilms 2147:2154 arg1 form 2139:2142 the dominant form 2126:2142 the dominant form of biofilms in nature 2126:2164 Multispecies biofilms are undoubtedly the dominant form of biofilms in nature. 36847543 12 10 theme biofilms 2147:2154 arg1 biofilms 2101:2108 Multispecies biofilms 2088:2108 Multispecies biofilms 2088:2108 Multispecies biofilms are undoubtedly the dominant form of biofilms in nature. 36847543 8 11 theme triple-species 1329:1342 arg1 biofilm 1344:1350 the triple-species biofilm 1325:1350 the triple-species biofilm 1325:1350 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 13 12 from need 2193:2196 arg1 development 2317:2327 development 2317:2327 development 2317:2327 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 13 12 from need 2193:2196 arg1 survival 2333:2340 survival 2333:2340 survival 2333:2340 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 13 13 theme biofilms 2267:2274 arg1 nature 2244:2249 the nature 2240:2249 the nature of multispecies biofilms 2240:2274 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 13 14 theme pressing 2184:2191 arg1 need 2193:2196 a pressing need 2182:2196 a pressing need for more research directed at delineating the nature of multispecies biofilms 2182:2274 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 9 15 theme biofilms 1834:1841 arg1 insights 1729:1736 novel insights 1723:1736 novel insights for further understanding interspecies interactions 1723:1788 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 9 15 theme biofilms 1834:1841 arg1 treatment 1807:1815 the clinical treatment 1794:1815 the clinical treatment of polymicrobial biofilms 1794:1841 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 13 16 dep development 2317:2327 arg1 the 2313:2315 the 2313:2315 the 2313:2315 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 6 17 from proportions 880:890 arg1 composition 966:976 the extracellular matrix (ECM) composition 935:976 the extracellular matrix (ECM) composition of the triple-species biofilm 935:1006 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 5 18 theme biofilm 775:781 arg1 biomass 783:789 the biofilm biomass 771:789 the biofilm biomass 771:789 Our results demonstrated that the coexistence of these three species enhanced the biofilm biomass and led to restructuring of the biofilm into a tower-like architecture. 36847543 10 19 theme lives 1953:1957 arg1 aspects 1932:1938 various aspects 1924:1938 various aspects of our daily lives 1924:1957 IMPORTANCE Bacterial biofilms possess distinct community properties that affect various aspects of our daily lives. 36847543 6 20 theme triple-species 985:998 arg1 biofilm 1000:1006 the triple-species biofilm 981:1006 the triple-species biofilm 981:1006 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 8 21 theme stress 1546:1551 arg1 regulators 1562:1571 versatile stress response regulators 1536:1571 versatile stress response regulators 1536:1571 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 8 22 theme nutrient 1365:1372 arg1 transport 1374:1382 nutrient transport 1365:1382 nutrient transport 1365:1382 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 15 23 theme potential 2619:2627 arg1 mechanisms 2640:2649 the potential underlying mechanisms 2615:2649 the potential underlying mechanisms that lead to the dominance of E. faecalis in triple-species biofilms 2615:2718 In combination with transcriptomic analyses, this pilot study explores the potential underlying mechanisms that lead to the dominance of E. faecalis in triple-species biofilms. 36847543 1 24 theme polymicrobial 149:161 arg1 biofilms 163:170 polymicrobial biofilms 149:170 polymicrobial biofilms 149:170 Chronic infections caused by polymicrobial biofilms are often difficult to treat effectively, partially due to the elevated tolerance of polymicrobial biofilms to antimicrobial treatments. 36847543 6 25 theme mono-species 1072:1083 arg1 biofilm 1085:1091 the E. faecalis mono-species biofilm 1056:1091 the E. faecalis mono-species biofilm 1056:1091 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 13 26 theme properties 2299:2308 arg1 need 2193:2196 a pressing need 2182:2196 a pressing need for more research directed at delineating the nature of multispecies biofilms 2182:2274 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 13 26 theme properties 2299:2308 arg1 effects 2284:2290 the effects 2280:2290 the effects of the properties on the development and survival of the biofilm community 2280:2365 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 15 27 theme pilot 2594:2598 arg1 study 2600:2604 this pilot study 2589:2604 this pilot study 2589:2604 In combination with transcriptomic analyses, this pilot study explores the potential underlying mechanisms that lead to the dominance of E. faecalis in triple-species biofilms. 36847543 9 28 theme study 1610:1614 arg1 results 1588:1594 the results 1584:1594 the results of this pilot study 1584:1614 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 6 29 theme E. 1060:1061 arg1 biofilm 1085:1091 the E. faecalis mono-species biofilm 1056:1091 the E. faecalis mono-species biofilm 1056:1091 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 8 30 theme acids 1410:1414 arg1 transport 1374:1382 nutrient transport 1365:1382 nutrient transport 1365:1382 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 8 30 theme acids 1410:1414 arg1 biosynthesis 1388:1399 biosynthesis 1388:1399 biosynthesis 1388:1399 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 5 31 theme biofilm 823:829 arg1 restructuring 802:814 restructuring 802:814 restructuring of the biofilm into a tower-like architecture 802:860 Our results demonstrated that the coexistence of these three species enhanced the biofilm biomass and led to restructuring of the biofilm into a tower-like architecture. 36847543 15 32 theme transcriptomic 2564:2577 arg1 analyses 2579:2586 transcriptomic analyses 2564:2586 transcriptomic analyses 2564:2586 In combination with transcriptomic analyses, this pilot study explores the potential underlying mechanisms that lead to the dominance of E. faecalis in triple-species biofilms. 36847543 15 33 theme faecalis 2684:2691 arg1 dominance 2668:2676 the dominance 2664:2676 the dominance of E. faecalis in triple-species biofilms 2664:2718 In combination with transcriptomic analyses, this pilot study explores the potential underlying mechanisms that lead to the dominance of E. faecalis in triple-species biofilms. 36847543 14 34 theme faecalis 2432:2439 arg1 coexistence 2404:2414 the coexistence 2400:2414 the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis 2400:2485 Here, we address the effects of the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis on triple-species biofilm formation with a static model. 36847543 0 35 theme Antimicrobial 98:110 arg1 Agents 112:117 Antimicrobial Agents 98:117 Antimicrobial Agents 98:117 The Coexistence of Bacterial Species Restructures Biofilm Architecture and Increases Tolerance to Antimicrobial Agents. 36847543 4 36 dep O157 620:623 arg1 coli 615:618 Escherichia coli O157:H7 603:626 Escherichia coli O157:H7 603:626 Here, we investigated the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation. 36847543 4 36 dep O157 620:623 arg1 H7 625:626 H7 625:626 Escherichia coli O157:H7 603:626 Here, we investigated the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation. 36847543 16 37 theme novel 2742:2746 arg1 insights 2748:2755 novel insights 2742:2755 novel insights into the nature of triple-species biofilms 2742:2798 Our findings provide novel insights into the nature of triple-species biofilms and indicate that the composition of multispecies biofilms should be a key consideration when determining antimicrobial treatments. 36847543 6 38 dep E. 1060:1061 arg1 faecalis 1063:1070 faecalis 1063:1070 faecalis 1063:1070 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 8 39 theme carbon 1438:1443 arg1 metabolism 1445:1454 central carbon metabolism 1430:1454 central carbon metabolism 1430:1454 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 9 40 theme faecalis-harboring 1640:1657 arg1 biofilms 1674:1681 E. faecalis-harboring triple-species biofilms 1637:1681 E. faecalis-harboring triple-species biofilms 1637:1681 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 3 41 theme polymicrobial 468:480 arg1 formation 490:498 polymicrobial biofilm formation 468:498 polymicrobial biofilm formation 468:498 However, the underlying role of the coexistence of bacterial species in polymicrobial biofilm formation is not fully understood. 36847543 7 42 theme triple-species 1223:1236 arg1 biofilm 1238:1244 the triple-species biofilm 1219:1244 the triple-species biofilm 1219:1244 Finally, we analyzed the transcriptomic profile of E. faecalis in response to coexistence with E. coli and S. enteritidis in the triple-species biofilm. 36847543 9 43 theme biofilms 1674:1681 arg1 nature 1627:1632 the nature 1623:1632 the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model 1623:1709 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 6 44 theme eDNAs 926:930 arg1 proportions 880:890 the proportions 876:890 the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm 876:1006 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 1 45 theme Chronic 120:126 arg1 infections 128:137 Chronic infections 120:137 Chronic infections caused by polymicrobial biofilms 120:170 Chronic infections caused by polymicrobial biofilms are often difficult to treat effectively, partially due to the elevated tolerance of polymicrobial biofilms to antimicrobial treatments. 36847543 3 46 theme species 457:463 arg1 coexistence 432:442 the coexistence 428:442 the coexistence of bacterial species 428:463 However, the underlying role of the coexistence of bacterial species in polymicrobial biofilm formation is not fully understood. 36847543 11 47 theme immune 2070:2075 arg1 responses 2077:2085 host immune responses 2065:2085 host immune responses 2065:2085 In particular, biofilms exhibit increased tolerance to chemical disinfectants, antimicrobial agents, and host immune responses. 36847543 0 48 theme Species 29:35 arg1 Coexistence 4:14 The Coexistence 0:14 The Coexistence of Bacterial Species 0:35 The Coexistence of Bacterial Species Restructures Biofilm Architecture and Increases Tolerance to Antimicrobial Agents. 36847543 12 49 from form 2139:2142 arg1 nature 2159:2164 nature 2159:2164 nature 2159:2164 Multispecies biofilms are undoubtedly the dominant form of biofilms in nature. 36847543 9 50 theme biofilm 1697:1703 arg1 model 1705:1709 a static biofilm model 1688:1709 a static biofilm model 1688:1709 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 14 51 from effects 2389:2395 arg1 formation 2513:2521 triple-species biofilm formation 2490:2521 triple-species biofilm formation with a static model 2490:2541 Here, we address the effects of the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis on triple-species biofilm formation with a static model. 36847543 4 52 theme coexistence 565:575 arg1 effect 551:556 the effect 547:556 the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation 547:690 Here, we investigated the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation. 36847543 8 53 theme biological 1500:1509 arg1 weapons 1511:1517 "biological weapons 1499:1517 "biological weapons 1499:1517 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 0 54 theme Biofilm 50:56 arg1 Architecture 58:69 Biofilm Architecture 50:69 Biofilm Architecture 50:69 The Coexistence of Bacterial Species Restructures Biofilm Architecture and Increases Tolerance to Antimicrobial Agents. 36847543 13 55 theme biofilm 2349:2355 arg1 community 2357:2365 the biofilm community 2345:2365 the biofilm community 2345:2365 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 14 56 with formation 2513:2521 arg1 model 2537:2541 a static model 2528:2541 a static model 2528:2541 Here, we address the effects of the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis on triple-species biofilm formation with a static model. 36847543 2 57 theme biofilm 377:383 arg1 formation 385:393 polymicrobial biofilm formation 363:393 polymicrobial biofilm formation 363:393 It is known that interspecific interactions influence polymicrobial biofilm formation. 36847543 1 58 theme elevated 235:242 arg1 tolerance 244:252 the elevated tolerance 231:252 the elevated tolerance of polymicrobial biofilms to antimicrobial treatments 231:306 Chronic infections caused by polymicrobial biofilms are often difficult to treat effectively, partially due to the elevated tolerance of polymicrobial biofilms to antimicrobial treatments. 36847543 9 59 theme novel 1723:1727 arg1 insights 1729:1736 novel insights 1723:1736 novel insights for further understanding interspecies interactions 1723:1788 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 16 60 theme multispecies 2837:2848 arg1 biofilms 2850:2857 multispecies biofilms 2837:2857 multispecies biofilms 2837:2857 Our findings provide novel insights into the nature of triple-species biofilms and indicate that the composition of multispecies biofilms should be a key consideration when determining antimicrobial treatments. 36847543 10 61 theme Bacterial 1855:1863 arg1 biofilms 1865:1872 IMPORTANCE Bacterial biofilms 1844:1872 IMPORTANCE Bacterial biofilms 1844:1872 IMPORTANCE Bacterial biofilms possess distinct community properties that affect various aspects of our daily lives. 36847543 1 62 theme biofilms 271:278 arg1 tolerance 244:252 the elevated tolerance 231:252 the elevated tolerance of polymicrobial biofilms to antimicrobial treatments 231:306 Chronic infections caused by polymicrobial biofilms are often difficult to treat effectively, partially due to the elevated tolerance of polymicrobial biofilms to antimicrobial treatments. 36847543 16 63 theme triple-species 2776:2789 arg1 biofilms 2791:2798 triple-species biofilms 2776:2798 triple-species biofilms 2776:2798 Our findings provide novel insights into the nature of triple-species biofilms and indicate that the composition of multispecies biofilms should be a key consideration when determining antimicrobial treatments. 36847543 4 64 from effect 551:556 arg1 formation 682:690 triple-species biofilm formation 659:690 triple-species biofilm formation 659:690 Here, we investigated the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation. 36847543 14 65 theme static 2530:2535 arg1 model 2537:2541 a static model 2528:2541 a static model 2528:2541 Here, we address the effects of the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis on triple-species biofilm formation with a static model. 36847543 1 66 theme antimicrobial 283:295 arg1 treatments 297:306 antimicrobial treatments 283:306 antimicrobial treatments 283:306 Chronic infections caused by polymicrobial biofilms are often difficult to treat effectively, partially due to the elevated tolerance of polymicrobial biofilms to antimicrobial treatments. 36847543 6 67 theme matrix 953:958 arg1 composition 966:976 the extracellular matrix (ECM) composition 935:976 the extracellular matrix (ECM) composition of the triple-species biofilm 935:1006 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 7 68 from profile 1134:1140 arg1 response 1160:1167 response 1160:1167 response to coexistence with E. coli and S. enteritidis in the triple-species biofilm 1160:1244 Finally, we analyzed the transcriptomic profile of E. faecalis in response to coexistence with E. coli and S. enteritidis in the triple-species biofilm. 36847543 7 69 theme faecalis 1148:1155 arg1 profile 1134:1140 the transcriptomic profile 1115:1140 the transcriptomic profile of E. faecalis in response to coexistence with E. coli and S. enteritidis in the triple-species biofilm 1115:1244 Finally, we analyzed the transcriptomic profile of E. faecalis in response to coexistence with E. coli and S. enteritidis in the triple-species biofilm. 36847543 10 70 theme community 1891:1899 arg1 properties 1901:1910 distinct community properties 1882:1910 distinct community properties that affect various aspects of our daily lives 1882:1957 IMPORTANCE Bacterial biofilms possess distinct community properties that affect various aspects of our daily lives. 36847543 4 71 theme faecalis 593:600 arg1 coexistence 565:575 the coexistence 561:575 the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis 561:654 Here, we investigated the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation. 36847543 14 72 theme biofilm 2505:2511 arg1 formation 2513:2521 triple-species biofilm formation 2490:2521 triple-species biofilm formation with a static model 2490:2541 Here, we address the effects of the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis on triple-species biofilm formation with a static model. 36847543 12 73 theme dominant 2130:2137 arg1 form 2139:2142 the dominant form 2126:2142 the dominant form of biofilms in nature 2126:2164 Multispecies biofilms are undoubtedly the dominant form of biofilms in nature. 36847543 12 73 theme dominant 2130:2137 arg1 biofilms 2101:2108 Multispecies biofilms 2088:2108 Multispecies biofilms 2088:2108 Multispecies biofilms are undoubtedly the dominant form of biofilms in nature. 36847543 5 74 theme species 754:760 arg1 coexistence 727:737 the coexistence 723:737 the coexistence of these three species 723:760 Our results demonstrated that the coexistence of these three species enhanced the biofilm biomass and led to restructuring of the biofilm into a tower-like architecture. 36847543 2 75 theme interspecific 326:338 arg1 interactions 340:351 interspecific interactions 326:351 interspecific interactions 326:351 It is known that interspecific interactions influence polymicrobial biofilm formation. 36847543 9 76 theme polymicrobial 1820:1832 arg1 biofilms 1834:1841 polymicrobial biofilms 1820:1841 polymicrobial biofilms 1820:1841 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 8 77 theme versatile 1536:1544 arg1 regulators 1562:1571 versatile stress response regulators 1536:1571 versatile stress response regulators 1536:1571 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 4 78 theme biofilm 674:680 arg1 formation 682:690 triple-species biofilm formation 659:690 triple-species biofilm formation 659:690 Here, we investigated the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation. 36847543 6 79 theme biofilm 1000:1006 arg1 composition 966:976 the extracellular matrix (ECM) composition 935:976 the extracellular matrix (ECM) composition of the triple-species biofilm 935:1006 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 8 80 theme response 1553:1560 arg1 regulators 1562:1571 versatile stress response regulators 1536:1571 versatile stress response regulators 1536:1571 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 9 81 with nature 1627:1632 arg1 model 1705:1709 a static biofilm model 1688:1709 a static biofilm model 1688:1709 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 10 82 theme daily 1947:1951 arg1 lives 1953:1957 our daily lives 1943:1957 our daily lives 1943:1957 IMPORTANCE Bacterial biofilms possess distinct community properties that affect various aspects of our daily lives. 36847543 7 83 theme transcriptomic 1119:1132 arg1 profile 1134:1140 the transcriptomic profile 1115:1140 the transcriptomic profile of E. faecalis in response to coexistence with E. coli and S. enteritidis in the triple-species biofilm 1115:1244 Finally, we analyzed the transcriptomic profile of E. faecalis in response to coexistence with E. coli and S. enteritidis in the triple-species biofilm. 36847543 14 84 theme enteritidis 2475:2485 arg1 coexistence 2404:2414 the coexistence 2400:2414 the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis 2400:2485 Here, we address the effects of the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis on triple-species biofilm formation with a static model. 36847543 15 85 theme underlying 2629:2638 arg1 mechanisms 2640:2649 the potential underlying mechanisms 2615:2649 the potential underlying mechanisms that lead to the dominance of E. faecalis in triple-species biofilms 2615:2718 In combination with transcriptomic analyses, this pilot study explores the potential underlying mechanisms that lead to the dominance of E. faecalis in triple-species biofilms. 36847543 10 86 theme various 1924:1930 arg1 aspects 1932:1938 various aspects 1924:1938 various aspects of our daily lives 1924:1957 IMPORTANCE Bacterial biofilms possess distinct community properties that affect various aspects of our daily lives. 36847543 10 87 contain possess 1874:1880 arg1 biofilms 1865:1872 IMPORTANCE Bacterial biofilms 1844:1872 IMPORTANCE Bacterial biofilms 1844:1872 IMPORTANCE Bacterial biofilms possess distinct community properties that affect various aspects of our daily lives. 36847543 10 87 contain possess 1874:1880 arg2 properties 1901:1910 distinct community properties 1882:1910 distinct community properties that affect various aspects of our daily lives 1882:1957 IMPORTANCE Bacterial biofilms possess distinct community properties that affect various aspects of our daily lives. 36847543 15 88 from dominance 2668:2676 arg1 biofilms 2711:2718 triple-species biofilms 2696:2718 triple-species biofilms 2696:2718 In combination with transcriptomic analyses, this pilot study explores the potential underlying mechanisms that lead to the dominance of E. faecalis in triple-species biofilms. 36847543 15 89 with combination 2547:2557 arg1 analyses 2579:2586 transcriptomic analyses 2564:2586 transcriptomic analyses 2564:2586 In combination with transcriptomic analyses, this pilot study explores the potential underlying mechanisms that lead to the dominance of E. faecalis in triple-species biofilms. 36847543 13 90 theme multispecies 2254:2265 arg1 biofilms 2267:2274 multispecies biofilms 2254:2274 multispecies biofilms 2254:2274 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 9 91 theme pilot 1604:1608 arg1 study 1610:1614 this pilot study 1599:1614 this pilot study 1599:1614 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 14 92 theme coli 2454:2457 arg1 coexistence 2404:2414 the coexistence 2400:2414 the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis 2400:2485 Here, we address the effects of the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis on triple-species biofilm formation with a static model. 36847543 3 93 from role 420:423 arg1 formation 490:498 polymicrobial biofilm formation 468:498 polymicrobial biofilm formation 468:498 However, the underlying role of the coexistence of bacterial species in polymicrobial biofilm formation is not fully understood. 36847543 8 94 theme amino 1404:1408 arg1 acids 1410:1414 amino acids 1404:1414 amino acids 1404:1414 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 12 95 theme Multispecies 2088:2099 arg1 form 2139:2142 the dominant form 2126:2142 the dominant form of biofilms in nature 2126:2164 Multispecies biofilms are undoubtedly the dominant form of biofilms in nature. 36847543 12 95 theme Multispecies 2088:2099 arg1 biofilms 2101:2108 Multispecies biofilms 2088:2108 Multispecies biofilms 2088:2108 Multispecies biofilms are undoubtedly the dominant form of biofilms in nature. 36847543 3 96 theme underlying 409:418 arg1 role 420:423 the underlying role 405:423 the underlying role of the coexistence of bacterial species in polymicrobial biofilm formation 405:498 However, the underlying role of the coexistence of bacterial species in polymicrobial biofilm formation is not fully understood. 36847543 2 97 theme polymicrobial 363:375 arg1 formation 385:393 polymicrobial biofilm formation 363:393 polymicrobial biofilm formation 363:393 It is known that interspecific interactions influence polymicrobial biofilm formation. 36847543 9 98 theme E. 1637:1638 arg1 biofilms 1674:1681 E. faecalis-harboring triple-species biofilms 1637:1681 E. faecalis-harboring triple-species biofilms 1637:1681 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 16 99 theme key 2871:2873 arg1 consideration 2875:2887 a key consideration 2869:2887 a key consideration 2869:2887 Our findings provide novel insights into the nature of triple-species biofilms and indicate that the composition of multispecies biofilms should be a key consideration when determining antimicrobial treatments. 36847543 16 99 theme key 2871:2873 arg1 composition 2822:2832 the composition 2818:2832 the composition of multispecies biofilms 2818:2857 Our findings provide novel insights into the nature of triple-species biofilms and indicate that the composition of multispecies biofilms should be a key consideration when determining antimicrobial treatments. 36847543 8 100 theme central 1430:1436 arg1 metabolism 1445:1454 central carbon metabolism 1430:1454 central carbon metabolism 1430:1454 The results suggested that E. faecalis established dominance and restructured the triple-species biofilm by enhancing nutrient transport and biosynthesis of amino acids, upregulating central carbon metabolism, manipulating the microenvironment through "biological weapons," and activating versatile stress response regulators. 36847543 14 101 theme coexistence 2404:2414 arg1 effects 2389:2395 the effects 2385:2395 the effects of the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis on triple-species biofilm formation with a static model 2385:2541 Here, we address the effects of the coexistence of Enterococcus faecalis, Escherichia coli, and Salmonella enteritidis on triple-species biofilm formation with a static model. 36847543 11 102 theme host 2065:2068 arg1 responses 2077:2085 host immune responses 2065:2085 host immune responses 2065:2085 In particular, biofilms exhibit increased tolerance to chemical disinfectants, antimicrobial agents, and host immune responses. 36847543 13 103 theme more 2202:2205 arg1 research 2207:2214 more research 2202:2214 more research directed at delineating the nature of multispecies biofilms 2202:2274 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 9 104 theme triple-species 1659:1672 arg1 biofilms 1674:1681 E. faecalis-harboring triple-species biofilms 1637:1681 E. faecalis-harboring triple-species biofilms 1637:1681 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 3 105 theme coexistence 432:442 arg1 role 420:423 the underlying role 405:423 the underlying role of the coexistence of bacterial species in polymicrobial biofilm formation 405:498 However, the underlying role of the coexistence of bacterial species in polymicrobial biofilm formation is not fully understood. 36847543 4 106 theme Escherichia 603:613 arg1 O157 620:623 O157 620:623 Escherichia coli O157:H7 603:626 Here, we investigated the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation. 36847543 3 107 theme biofilm 482:488 arg1 formation 490:498 polymicrobial biofilm formation 468:498 polymicrobial biofilm formation 468:498 However, the underlying role of the coexistence of bacterial species in polymicrobial biofilm formation is not fully understood. 36847543 0 108 theme Bacterial 19:27 arg1 Species 29:35 Bacterial Species 19:35 Bacterial Species 19:35 The Coexistence of Bacterial Species Restructures Biofilm Architecture and Increases Tolerance to Antimicrobial Agents. 36847543 16 109 theme antimicrobial 2906:2918 arg1 treatments 2920:2929 antimicrobial treatments 2906:2929 antimicrobial treatments 2906:2929 Our findings provide novel insights into the nature of triple-species biofilms and indicate that the composition of multispecies biofilms should be a key consideration when determining antimicrobial treatments. 36847543 4 110 theme O157 620:623 arg1 coexistence 565:575 the coexistence 561:575 the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis 561:654 Here, we investigated the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation. 36847543 9 111 theme static 1690:1695 arg1 model 1705:1709 a static biofilm model 1688:1709 a static biofilm model 1688:1709 Together, the results of this pilot study reveal the nature of E. faecalis-harboring triple-species biofilms with a static biofilm model and provide novel insights for further understanding interspecies interactions and the clinical treatment of polymicrobial biofilms. 36847543 5 112 theme tower-like 838:847 arg1 architecture 849:860 a tower-like architecture 836:860 a tower-like architecture 836:860 Our results demonstrated that the coexistence of these three species enhanced the biofilm biomass and led to restructuring of the biofilm into a tower-like architecture. 36847543 16 113 theme biofilms 2791:2798 arg1 nature 2766:2771 the nature 2762:2771 the nature of triple-species biofilms 2762:2798 Our findings provide novel insights into the nature of triple-species biofilms and indicate that the composition of multispecies biofilms should be a key consideration when determining antimicrobial treatments. 36847543 6 114 theme proteins 912:919 arg1 proportions 880:890 the proportions 876:890 the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm 876:1006 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 3 115 theme bacterial 447:455 arg1 species 457:463 bacterial species 447:463 bacterial species 447:463 However, the underlying role of the coexistence of bacterial species in polymicrobial biofilm formation is not fully understood. 36847543 7 116 from coexistence 1172:1182 arg1 biofilm 1238:1244 the triple-species biofilm 1219:1244 the triple-species biofilm 1219:1244 Finally, we analyzed the transcriptomic profile of E. faecalis in response to coexistence with E. coli and S. enteritidis in the triple-species biofilm. 36847543 13 117 theme community 2357:2365 arg1 development 2317:2327 development 2317:2327 development 2317:2327 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 13 117 theme community 2357:2365 arg1 survival 2333:2340 survival 2333:2340 survival 2333:2340 Thus, there is a pressing need for more research directed at delineating the nature of multispecies biofilms and the effects of the properties on the development and survival of the biofilm community. 36847543 6 118 theme polysaccharides 895:909 arg1 proportions 880:890 the proportions 876:890 the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm 876:1006 Furthermore, the proportions of polysaccharides, proteins, and eDNAs in the extracellular matrix (ECM) composition of the triple-species biofilm were significantly changed compared to those in the E. faecalis mono-species biofilm. 36847543 4 119 theme enteritidis 644:654 arg1 coexistence 565:575 the coexistence 561:575 the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis 561:654 Here, we investigated the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation. 36847543 11 120 theme increased 1992:2000 arg1 tolerance 2002:2010 increased tolerance 1992:2010 increased tolerance to chemical disinfectants, antimicrobial agents, and host immune responses 1992:2085 In particular, biofilms exhibit increased tolerance to chemical disinfectants, antimicrobial agents, and host immune responses. 36847543 16 121 theme biofilms 2850:2857 arg1 composition 2822:2832 the composition 2818:2832 the composition of multispecies biofilms 2818:2857 Our findings provide novel insights into the nature of triple-species biofilms and indicate that the composition of multispecies biofilms should be a key consideration when determining antimicrobial treatments. 36847543 16 121 theme biofilms 2850:2857 arg1 consideration 2875:2887 a key consideration 2869:2887 a key consideration 2869:2887 Our findings provide novel insights into the nature of triple-species biofilms and indicate that the composition of multispecies biofilms should be a key consideration when determining antimicrobial treatments. 36847543 4 122 theme triple-species 659:672 arg1 formation 682:690 triple-species biofilm formation 659:690 triple-species biofilm formation 659:690 Here, we investigated the effect of the coexistence of Enterococcus faecalis, Escherichia coli O157:H7, and Salmonella enteritidis on triple-species biofilm formation. 36847543 11 123 theme antimicrobial 2039:2051 arg1 agents 2053:2058 antimicrobial agents 2039:2058 antimicrobial agents 2039:2058 In particular, biofilms exhibit increased tolerance to chemical disinfectants, antimicrobial agents, and host immune responses. 36847543 1 124 theme polymicrobial 257:269 arg1 biofilms 271:278 polymicrobial biofilms 257:278 polymicrobial biofilms 257:278 Chronic infections caused by polymicrobial biofilms are often difficult to treat effectively, partially due to the elevated tolerance of polymicrobial biofilms to antimicrobial treatments. 35761712 0 0 theme different 90:98 arg1 methods 113:119 different modification methods 90:119 different modification methods 90:119 Physicochemical structure and functional properties of soluble dietary fibers obtained by different modification methods from Mesona chinensis Benth. 35761712 7 1 theme thermal 1041:1047 arg1 stability 1049:1057 thermal stability 1041:1057 thermal stability 1041:1057 In contrast to HE-SDF and HU-SDF, A-SDF exhibited a dense wavy microstructure, and elevated crystallinity and thermal stability. 35761712 8 2 theme monosaccharide 1077:1090 arg1 composition 1092:1102 monosaccharide composition 1077:1102 monosaccharide composition 1077:1102 In addition, the monosaccharide composition and molecular weight of HU-SDF, HE-SDF and A-SDF were significantly altered as compared to CK-SDF. 35761712 3 3 theme A-SDF 475:479 arg1 properties 461:470 the structural and in vitro functional properties 422:470 the structural and in vitro functional properties of A-SDF, HU-SDF and HE-SDF 422:498 residue (MCBR), then the structural and in vitro functional properties of A-SDF, HU-SDF and HE-SDF were investigated. 35761712 5 4 theme molecular 686:694 arg1 distribution 703:714 molecular weight distribution 686:714 molecular weight distribution 686:714 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 5 5 theme FT-IR 632:636 arg1 analysis 738:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 6 6 theme control 816:822 arg1 CK-SDF 829:834 CK-SDF 829:834 CK-SDF 829:834 Compared with the control SDF (CK-SDF), HE-SDF and HU-SDF had looser and more porous microstructure, as well as lower crystallinity. 35761712 6 6 theme control 816:822 arg1 SDF 824:826 the control SDF 812:826 the control SDF (CK-SDF) 812:835 Compared with the control SDF (CK-SDF), HE-SDF and HU-SDF had looser and more porous microstructure, as well as lower crystallinity. 35761712 2 7 theme dietary 354:360 arg1 fiber 362:366 soluble dietary fiber 346:366 soluble dietary fiber (SDF) 346:372 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 7 theme dietary 354:360 arg1 SDF 369:371 SDF 369:371 SDF 369:371 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 11 8 from additives 1861:1869 arg1 food 1874:1877 food 1874:1877 food 1874:1877 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 6 9 theme porous 876:881 arg1 microstructure 883:896 looser and more porous microstructure 860:896 looser and more porous microstructure 860:896 Compared with the control SDF (CK-SDF), HE-SDF and HU-SDF had looser and more porous microstructure, as well as lower crystallinity. 35761712 9 10 theme nitrite 1452:1458 arg1 NIAC 1485:1488 NIAC 1485:1488 NIAC 1485:1488 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 10 theme nitrite 1452:1458 arg1 capacity 1475:1482 nitrite ion adsorption capacity 1452:1482 nitrite ion adsorption capacity (NIAC) 1452:1489 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 11 theme adsorption 1464:1473 arg1 NIAC 1485:1488 NIAC 1485:1488 NIAC 1485:1488 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 11 theme adsorption 1464:1473 arg1 capacity 1475:1482 nitrite ion adsorption capacity 1452:1482 nitrite ion adsorption capacity (NIAC) 1452:1489 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 0 12 theme modification 100:111 arg1 methods 113:119 different modification methods 90:119 different modification methods 90:119 Physicochemical structure and functional properties of soluble dietary fibers obtained by different modification methods from Mesona chinensis Benth. 35761712 9 13 theme water 1271:1275 arg1 WHC 1295:1297 WHC 1295:1297 WHC 1295:1297 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 13 theme water 1271:1275 arg1 capacity 1285:1292 water holding capacity 1271:1292 water holding capacity (WHC) 1271:1298 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 5 14 theme monosaccharide 639:652 arg1 composition 654:664 monosaccharide composition 639:664 monosaccharide composition 639:664 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 2 15 theme enzyme 301:306 arg1 HTCE 320:323 HTCE 320:323 HTCE 320:323 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 15 theme enzyme 301:306 arg1 hydrolysis 308:317 complex enzyme hydrolysis 293:317 complex enzyme hydrolysis (HTCE) 293:324 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 5 16 theme stability 728:736 arg1 analysis 738:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 2 17 theme hydrogen 168:175 arg1 cooking 210:216 high-temperature cooking 193:216 high-temperature cooking 193:216 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 17 theme hydrogen 168:175 arg1 AHP 187:189 AHP 187:189 AHP 187:189 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 17 theme hydrogen 168:175 arg1 peroxide 177:184 Alkaline hydrogen peroxide 159:184 Alkaline hydrogen peroxide (AHP) 159:190 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 3 18 theme HE-SDF 493:498 arg1 properties 461:470 the structural and in vitro functional properties 422:470 the structural and in vitro functional properties of A-SDF, HU-SDF and HE-SDF 422:498 residue (MCBR), then the structural and in vitro functional properties of A-SDF, HU-SDF and HE-SDF were investigated. 35761712 10 19 theme dense 1553:1557 arg1 structure 1559:1567 dense structure 1553:1567 dense structure 1553:1567 However, the dense structure and high crystallinity of A-SDF resulted in a significantly lower GAC and NIAC than that of CK-SDF, with only WHC and α-AAIR being improved. 35761712 8 20 theme HE-SDF 1136:1141 arg1 weight 1118:1123 molecular weight 1108:1123 molecular weight 1108:1123 In addition, the monosaccharide composition and molecular weight of HU-SDF, HE-SDF and A-SDF were significantly altered as compared to CK-SDF. 35761712 8 20 theme HE-SDF 1136:1141 arg1 composition 1092:1102 monosaccharide composition 1077:1102 monosaccharide composition 1077:1102 In addition, the monosaccharide composition and molecular weight of HU-SDF, HE-SDF and A-SDF were significantly altered as compared to CK-SDF. 35761712 2 21 theme Alkaline 159:166 arg1 cooking 210:216 high-temperature cooking 193:216 high-temperature cooking 193:216 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 21 theme Alkaline 159:166 arg1 AHP 187:189 AHP 187:189 AHP 187:189 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 21 theme Alkaline 159:166 arg1 peroxide 177:184 Alkaline hydrogen peroxide 159:184 Alkaline hydrogen peroxide (AHP) 159:190 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 5 22 theme Scanning 602:609 arg1 microscopy 620:629 Scanning electron microscopy 602:629 Scanning electron microscopy 602:629 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 2 23 used used 331:334 arg2 peroxide 177:184 Alkaline hydrogen peroxide 159:184 Alkaline hydrogen peroxide (AHP) 159:190 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 23 used used 331:334 arg2 cooking 210:216 high-temperature cooking 193:216 high-temperature cooking 193:216 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 23 used used 331:334 arg2 AHP 187:189 AHP 187:189 AHP 187:189 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 8 24 theme A-SDF 1147:1151 arg1 weight 1118:1123 molecular weight 1108:1123 molecular weight 1108:1123 In addition, the monosaccharide composition and molecular weight of HU-SDF, HE-SDF and A-SDF were significantly altered as compared to CK-SDF. 35761712 8 24 theme A-SDF 1147:1151 arg1 composition 1092:1102 monosaccharide composition 1077:1102 monosaccharide composition 1077:1102 In addition, the monosaccharide composition and molecular weight of HU-SDF, HE-SDF and A-SDF were significantly altered as compared to CK-SDF. 35761712 7 25 theme wavy 989:992 arg1 microstructure 994:1007 a dense wavy microstructure 981:1007 a dense wavy microstructure 981:1007 In contrast to HE-SDF and HU-SDF, A-SDF exhibited a dense wavy microstructure, and elevated crystallinity and thermal stability. 35761712 8 26 dep composition 1092:1102 arg1 the 1073:1075 the 1073:1075 the 1073:1075 In addition, the monosaccharide composition and molecular weight of HU-SDF, HE-SDF and A-SDF were significantly altered as compared to CK-SDF. 35761712 9 27 theme HE-SDF 1242:1247 arg1 higher 1511:1516 higher 1511:1516 higher 1511:1516 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 27 theme HE-SDF 1242:1247 arg1 capacity 1285:1292 water holding capacity 1271:1292 water holding capacity (WHC) 1271:1298 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 27 theme HE-SDF 1242:1247 arg1 capacity 1313:1320 oil holding capacity 1301:1320 oil holding capacity (OHC) 1301:1326 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 27 theme HE-SDF 1242:1247 arg1 capacity 1348:1355 glucose adsorption capacity 1329:1355 glucose adsorption capacity (GAC) 1329:1361 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 27 theme HE-SDF 1242:1247 arg1 capacity 1433:1440 cholesterol adsorption capacity 1410:1440 cholesterol adsorption capacity (CAC) 1410:1446 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 27 theme HE-SDF 1242:1247 arg1 ratio 1394:1398 α-amylase activity inhibition ratio 1364:1398 α-amylase activity inhibition ratio (α-AAIR) 1364:1407 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 27 theme HE-SDF 1242:1247 arg1 properties 1228:1237 the functional properties 1213:1237 the functional properties 1213:1237 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 27 theme HE-SDF 1242:1247 arg1 capacity 1475:1482 nitrite ion adsorption capacity 1452:1482 nitrite ion adsorption capacity (NIAC) 1452:1489 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 5 28 theme electron 611:618 arg1 microscopy 620:629 Scanning electron microscopy 602:629 Scanning electron microscopy 602:629 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 11 29 theme modification 1779:1790 arg1 methods 1792:1798 ideal modification methods 1773:1798 ideal modification methods for MCBR SDF, HE-SDF and HU-SDF 1773:1830 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 9 30 theme holding 1277:1283 arg1 WHC 1295:1297 WHC 1295:1297 WHC 1295:1297 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 30 theme holding 1277:1283 arg1 capacity 1285:1292 water holding capacity 1271:1292 water holding capacity (WHC) 1271:1298 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 31 theme activity 1374:1381 arg1 α-AAIR 1401:1406 α-AAIR 1401:1406 α-AAIR 1401:1406 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 31 theme activity 1374:1381 arg1 ratio 1394:1398 α-amylase activity inhibition ratio 1364:1398 α-amylase activity inhibition ratio (α-AAIR) 1364:1407 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 0 32 theme Physicochemical 0:14 arg1 structure 16:24 Physicochemical structure 0:24 Physicochemical structure 0:24 Physicochemical structure and functional properties of soluble dietary fibers obtained by different modification methods from Mesona chinensis Benth. 35761712 5 33 theme microscopy 620:629 arg1 analysis 738:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 7 34 dep HE-SDF 946:951 arg1 contrast 934:941 contrast 934:941 contrast 934:941 In contrast to HE-SDF and HU-SDF, A-SDF exhibited a dense wavy microstructure, and elevated crystallinity and thermal stability. 35761712 9 35 theme inhibition 1383:1392 arg1 α-AAIR 1401:1406 α-AAIR 1401:1406 α-AAIR 1401:1406 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 35 theme inhibition 1383:1392 arg1 ratio 1394:1398 α-amylase activity inhibition ratio 1364:1398 α-amylase activity inhibition ratio (α-AAIR) 1364:1407 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 0 36 theme functional 30:39 arg1 properties 41:50 functional properties 30:50 functional properties 30:50 Physicochemical structure and functional properties of soluble dietary fibers obtained by different modification methods from Mesona chinensis Benth. 35761712 10 37 theme lower 1629:1633 arg1 GAC 1635:1637 GAC 1635:1637 GAC 1635:1637 However, the dense structure and high crystallinity of A-SDF resulted in a significantly lower GAC and NIAC than that of CK-SDF, with only WHC and α-AAIR being improved. 35761712 6 38 contain had 856:858 arg1 HE-SDF 838:843 HE-SDF 838:843 HE-SDF 838:843 Compared with the control SDF (CK-SDF), HE-SDF and HU-SDF had looser and more porous microstructure, as well as lower crystallinity. 35761712 6 38 contain had 856:858 arg2 microstructure 883:896 looser and more porous microstructure 860:896 looser and more porous microstructure 860:896 Compared with the control SDF (CK-SDF), HE-SDF and HU-SDF had looser and more porous microstructure, as well as lower crystallinity. 35761712 6 38 contain had 856:858 arg2 crystallinity 916:928 lower crystallinity 910:928 lower crystallinity 910:928 Compared with the control SDF (CK-SDF), HE-SDF and HU-SDF had looser and more porous microstructure, as well as lower crystallinity. 35761712 6 38 contain had 856:858 arg1 HU-SDF 849:854 HU-SDF 849:854 HU-SDF 849:854 Compared with the control SDF (CK-SDF), HE-SDF and HU-SDF had looser and more porous microstructure, as well as lower crystallinity. 35761712 11 39 contain have 1832:1835 arg2 potential 1837:1845 potential 1837:1845 potential 1837:1845 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 11 39 contain have 1832:1835 arg1 methods 1792:1798 ideal modification methods 1773:1798 ideal modification methods for MCBR SDF, HE-SDF and HU-SDF 1773:1830 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 11 39 contain have 1832:1835 arg2 additives 1861:1869 functional additives 1850:1869 functional additives in food 1850:1877 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 2 40 theme complex 293:299 arg1 HTCE 320:323 HTCE 320:323 HTCE 320:323 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 40 theme complex 293:299 arg1 hydrolysis 308:317 complex enzyme hydrolysis 293:317 complex enzyme hydrolysis (HTCE) 293:324 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 10 41 theme high 1573:1576 arg1 crystallinity 1578:1590 high crystallinity 1573:1590 high crystallinity 1573:1590 However, the dense structure and high crystallinity of A-SDF resulted in a significantly lower GAC and NIAC than that of CK-SDF, with only WHC and α-AAIR being improved. 35761712 9 42 theme oil 1301:1303 arg1 capacity 1313:1320 oil holding capacity 1301:1320 oil holding capacity (OHC) 1301:1326 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 42 theme oil 1301:1303 arg1 OHC 1323:1325 OHC 1323:1325 OHC 1323:1325 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 5 43 theme weight 696:701 arg1 distribution 703:714 molecular weight distribution 686:714 molecular weight distribution 686:714 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 11 44 theme ideal 1773:1777 arg1 methods 1792:1798 ideal modification methods 1773:1798 ideal modification methods for MCBR SDF, HE-SDF and HU-SDF 1773:1830 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 11 45 used used 1765:1768 arg2 HTCE 1751:1754 HTCE 1751:1754 HTCE 1751:1754 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 11 45 used used 1765:1768 arg2 HTCU 1742:1745 HTCU 1742:1745 HTCU 1742:1745 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 5 46 theme structural 778:787 arg1 changes 789:795 the structural changes 774:795 the structural changes 774:795 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 9 47 theme holding 1305:1311 arg1 capacity 1313:1320 oil holding capacity 1301:1320 oil holding capacity (OHC) 1301:1326 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 47 theme holding 1305:1311 arg1 OHC 1323:1325 OHC 1323:1325 OHC 1323:1325 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 5 48 theme distribution 703:714 arg1 analysis 738:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 9 49 theme glucose 1329:1335 arg1 GAC 1358:1360 GAC 1358:1360 GAC 1358:1360 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 49 theme glucose 1329:1335 arg1 capacity 1348:1355 glucose adsorption capacity 1329:1355 glucose adsorption capacity (GAC) 1329:1361 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 3 50 theme structural 426:435 arg1 properties 461:470 the structural and in vitro functional properties 422:470 the structural and in vitro functional properties of A-SDF, HU-SDF and HE-SDF 422:498 residue (MCBR), then the structural and in vitro functional properties of A-SDF, HU-SDF and HE-SDF were investigated. 35761712 0 51 theme dietary 63:69 arg1 fibers 71:76 soluble dietary fibers 55:76 soluble dietary fibers 55:76 Physicochemical structure and functional properties of soluble dietary fibers obtained by different modification methods from Mesona chinensis Benth. 35761712 6 52 theme lower 910:914 arg1 crystallinity 916:928 lower crystallinity 910:928 lower crystallinity 910:928 Compared with the control SDF (CK-SDF), HE-SDF and HU-SDF had looser and more porous microstructure, as well as lower crystallinity. 35761712 5 53 theme composition 654:664 arg1 analysis 738:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 11 54 theme MCBR 1804:1807 arg1 SDF 1809:1811 MCBR SDF 1804:1811 MCBR SDF 1804:1811 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 6 55 theme looser 860:865 arg1 microstructure 883:896 looser and more porous microstructure 860:896 looser and more porous microstructure 860:896 Compared with the control SDF (CK-SDF), HE-SDF and HU-SDF had looser and more porous microstructure, as well as lower crystallinity. 35761712 2 56 theme soluble 346:352 arg1 fiber 362:366 soluble dietary fiber 346:366 soluble dietary fiber (SDF) 346:372 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 56 theme soluble 346:352 arg1 SDF 369:371 SDF 369:371 SDF 369:371 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 0 57 theme soluble 55:61 arg1 fibers 71:76 soluble dietary fibers 55:76 soluble dietary fibers 55:76 Physicochemical structure and functional properties of soluble dietary fibers obtained by different modification methods from Mesona chinensis Benth. 35761712 9 58 theme functional 1217:1226 arg1 higher 1511:1516 higher 1511:1516 higher 1511:1516 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 58 theme functional 1217:1226 arg1 capacity 1285:1292 water holding capacity 1271:1292 water holding capacity (WHC) 1271:1298 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 58 theme functional 1217:1226 arg1 capacity 1313:1320 oil holding capacity 1301:1320 oil holding capacity (OHC) 1301:1326 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 58 theme functional 1217:1226 arg1 capacity 1348:1355 glucose adsorption capacity 1329:1355 glucose adsorption capacity (GAC) 1329:1361 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 58 theme functional 1217:1226 arg1 capacity 1433:1440 cholesterol adsorption capacity 1410:1440 cholesterol adsorption capacity (CAC) 1410:1446 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 58 theme functional 1217:1226 arg1 ratio 1394:1398 α-amylase activity inhibition ratio 1364:1398 α-amylase activity inhibition ratio (α-AAIR) 1364:1407 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 58 theme functional 1217:1226 arg1 properties 1228:1237 the functional properties 1213:1237 the functional properties 1213:1237 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 58 theme functional 1217:1226 arg1 capacity 1475:1482 nitrite ion adsorption capacity 1452:1482 nitrite ion adsorption capacity (NIAC) 1452:1489 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 59 theme HU-SDF 1253:1258 arg1 higher 1511:1516 higher 1511:1516 higher 1511:1516 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 59 theme HU-SDF 1253:1258 arg1 capacity 1285:1292 water holding capacity 1271:1292 water holding capacity (WHC) 1271:1298 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 59 theme HU-SDF 1253:1258 arg1 capacity 1313:1320 oil holding capacity 1301:1320 oil holding capacity (OHC) 1301:1326 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 59 theme HU-SDF 1253:1258 arg1 capacity 1348:1355 glucose adsorption capacity 1329:1355 glucose adsorption capacity (GAC) 1329:1361 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 59 theme HU-SDF 1253:1258 arg1 capacity 1433:1440 cholesterol adsorption capacity 1410:1440 cholesterol adsorption capacity (CAC) 1410:1446 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 59 theme HU-SDF 1253:1258 arg1 ratio 1394:1398 α-amylase activity inhibition ratio 1364:1398 α-amylase activity inhibition ratio (α-AAIR) 1364:1407 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 59 theme HU-SDF 1253:1258 arg1 properties 1228:1237 the functional properties 1213:1237 the functional properties 1213:1237 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 59 theme HU-SDF 1253:1258 arg1 capacity 1475:1482 nitrite ion adsorption capacity 1452:1482 nitrite ion adsorption capacity (NIAC) 1452:1489 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 60 theme cholesterol 1410:1420 arg1 CAC 1443:1445 CAC 1443:1445 CAC 1443:1445 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 60 theme cholesterol 1410:1420 arg1 capacity 1433:1440 cholesterol adsorption capacity 1410:1440 cholesterol adsorption capacity (CAC) 1410:1446 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 5 61 theme X-ray 667:671 arg1 diffraction 673:683 X-ray diffraction 667:683 X-ray diffraction 667:683 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 8 62 theme HU-SDF 1128:1133 arg1 weight 1118:1123 molecular weight 1108:1123 molecular weight 1108:1123 In addition, the monosaccharide composition and molecular weight of HU-SDF, HE-SDF and A-SDF were significantly altered as compared to CK-SDF. 35761712 8 62 theme HU-SDF 1128:1133 arg1 composition 1092:1102 monosaccharide composition 1077:1102 monosaccharide composition 1077:1102 In addition, the monosaccharide composition and molecular weight of HU-SDF, HE-SDF and A-SDF were significantly altered as compared to CK-SDF. 35761712 10 63 dep structure 1559:1567 arg1 the 1549:1551 the 1549:1551 the 1549:1551 However, the dense structure and high crystallinity of A-SDF resulted in a significantly lower GAC and NIAC than that of CK-SDF, with only WHC and α-AAIR being improved. 35761712 9 64 theme adsorption 1422:1431 arg1 CAC 1443:1445 CAC 1443:1445 CAC 1443:1445 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 64 theme adsorption 1422:1431 arg1 capacity 1433:1440 cholesterol adsorption capacity 1410:1440 cholesterol adsorption capacity (CAC) 1410:1446 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 11 65 theme functional 1850:1859 arg1 additives 1861:1869 functional additives 1850:1869 functional additives in food 1850:1877 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 11 65 theme functional 1850:1859 arg1 potential 1837:1845 potential 1837:1845 potential 1837:1845 Overall, this study showed that HTCU and HTCE could be used as ideal modification methods for MCBR SDF, HE-SDF and HU-SDF have potential as functional additives in food. 35761712 5 66 theme diffraction 673:683 arg1 analysis 738:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis 602:745 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 35761712 7 67 theme dense 983:987 arg1 microstructure 994:1007 a dense wavy microstructure 981:1007 a dense wavy microstructure 981:1007 In contrast to HE-SDF and HU-SDF, A-SDF exhibited a dense wavy microstructure, and elevated crystallinity and thermal stability. 35761712 3 68 theme functional 450:459 arg1 properties 461:470 the structural and in vitro functional properties 422:470 the structural and in vitro functional properties of A-SDF, HU-SDF and HE-SDF 422:498 residue (MCBR), then the structural and in vitro functional properties of A-SDF, HU-SDF and HE-SDF were investigated. 35761712 10 69 theme A-SDF 1595:1599 arg1 structure 1559:1567 dense structure 1553:1567 dense structure 1553:1567 However, the dense structure and high crystallinity of A-SDF resulted in a significantly lower GAC and NIAC than that of CK-SDF, with only WHC and α-AAIR being improved. 35761712 10 69 theme A-SDF 1595:1599 arg1 crystallinity 1578:1590 high crystallinity 1573:1590 high crystallinity 1573:1590 However, the dense structure and high crystallinity of A-SDF resulted in a significantly lower GAC and NIAC than that of CK-SDF, with only WHC and α-AAIR being improved. 35761712 8 70 theme molecular 1108:1116 arg1 weight 1118:1123 molecular weight 1108:1123 molecular weight 1108:1123 In addition, the monosaccharide composition and molecular weight of HU-SDF, HE-SDF and A-SDF were significantly altered as compared to CK-SDF. 35761712 2 71 theme high-temperature 193:208 arg1 cooking 210:216 high-temperature cooking 193:216 high-temperature cooking 193:216 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 71 theme high-temperature 193:208 arg1 peroxide 177:184 Alkaline hydrogen peroxide 159:184 Alkaline hydrogen peroxide (AHP) 159:190 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 2 72 theme high-temperature 254:269 arg1 cooking 271:277 ultrasonic (HTCU) and high-temperature cooking 232:277 cooking 271:277 Alkaline hydrogen peroxide (AHP), high-temperature cooking combined with ultrasonic (HTCU) and high-temperature cooking combined with complex enzyme hydrolysis (HTCE) were used to modify soluble dietary fiber (SDF) in Mesona chinensis Benth. 35761712 3 73 theme HU-SDF 482:487 arg1 properties 461:470 the structural and in vitro functional properties 422:470 the structural and in vitro functional properties of A-SDF, HU-SDF and HE-SDF 422:498 residue (MCBR), then the structural and in vitro functional properties of A-SDF, HU-SDF and HE-SDF were investigated. 35761712 9 74 theme α-amylase 1364:1372 arg1 α-AAIR 1401:1406 α-AAIR 1401:1406 α-AAIR 1401:1406 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 74 theme α-amylase 1364:1372 arg1 ratio 1394:1398 α-amylase activity inhibition ratio 1364:1398 α-amylase activity inhibition ratio (α-AAIR) 1364:1407 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 4 75 theme SDF 597:599 arg1 yield 588:592 the yield 584:592 the yield of SDF 584:599 Results showed that the three treatments significantly increased the yield of SDF. 35761712 0 76 theme fibers 71:76 arg1 structure 16:24 Physicochemical structure 0:24 Physicochemical structure 0:24 Physicochemical structure and functional properties of soluble dietary fibers obtained by different modification methods from Mesona chinensis Benth. 35761712 0 76 theme fibers 71:76 arg1 properties 41:50 functional properties 30:50 functional properties 30:50 Physicochemical structure and functional properties of soluble dietary fibers obtained by different modification methods from Mesona chinensis Benth. 35761712 9 77 theme adsorption 1337:1346 arg1 GAC 1358:1360 GAC 1358:1360 GAC 1358:1360 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 77 theme adsorption 1337:1346 arg1 capacity 1348:1355 glucose adsorption capacity 1329:1355 glucose adsorption capacity (GAC) 1329:1361 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 78 theme ion 1460:1462 arg1 NIAC 1485:1488 NIAC 1485:1488 NIAC 1485:1488 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 9 78 theme ion 1460:1462 arg1 capacity 1475:1482 nitrite ion adsorption capacity 1452:1482 nitrite ion adsorption capacity (NIAC) 1452:1489 Moreover, the functional properties of HE-SDF and HU-SDF, including water holding capacity (WHC), oil holding capacity (OHC), glucose adsorption capacity (GAC), α-amylase activity inhibition ratio (α-AAIR), cholesterol adsorption capacity (CAC) and nitrite ion adsorption capacity (NIAC), were significantly higher than those of CK-SDF. 35761712 5 79 theme thermal 720:726 arg1 stability 728:736 thermal stability 720:736 thermal stability 720:736 Scanning electron microscopy, FT-IR, monosaccharide composition, X-ray diffraction, molecular weight distribution and thermal stability analysis were employed to determine the structural changes. 36359985 6 0 theme glycosidic 1029:1038 arg1 vibration 1045:1053 glycosidic bond vibration 1029:1053 glycosidic bond vibration 1029:1053 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 10 1 from regions 1519:1525 arg1 sample 1534:1539 the sample 1530:1539 the sample 1530:1539 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 8 2 contain had 1203:1205 arg1 micrographs 1164:1174 SEM micrographs 1160:1174 SEM micrographs of ferulated arabinoxylans 1160:1201 Moreover, SEM micrographs of ferulated arabinoxylans had visible rough and porous surface morphology. 36359985 8 2 contain had 1203:1205 arg2 morphology 1240:1249 visible rough and porous surface morphology 1207:1249 visible rough and porous surface morphology 1207:1249 Moreover, SEM micrographs of ferulated arabinoxylans had visible rough and porous surface morphology. 36359985 2 3 theme maize 311:315 arg1 NMB 323:325 NMB 323:325 NMB 323:325 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 3 theme maize 311:315 arg1 bran 317:320 nixtamalized maize bran 298:320 nixtamalized maize bran (NMB) 298:326 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 4 4 theme arabinoxylans 675:687 arg1 % 703:703 60.1 ± 0.8% 693:703 60.1 ± 0.8% 693:703 Moreover, the purity of arabinoxylans was 60.1 ± 0.8% and 57.04 ± 0.7% in NMB and NNMB ferulated arabinoxylans. 36359985 4 4 theme arabinoxylans 675:687 arg1 purity 665:670 the purity 661:670 the purity of arabinoxylans 661:687 Moreover, the purity of arabinoxylans was 60.1 ± 0.8% and 57.04 ± 0.7% in NMB and NNMB ferulated arabinoxylans. 36359985 9 5 theme amorphous 1368:1376 arg1 nature 1378:1383 their amorphous nature 1362:1383 their amorphous nature 1362:1383 Further, ferulated arabinoxylans of NMB and NNMB did not exhibit any sharp peaks in XRD graphs, attributed to their amorphous nature. 36359985 8 6 theme arabinoxylans 1189:1201 arg1 micrographs 1164:1174 SEM micrographs 1160:1174 SEM micrographs of ferulated arabinoxylans 1160:1201 Moreover, SEM micrographs of ferulated arabinoxylans had visible rough and porous surface morphology. 36359985 3 7 theme arabinoxylans 574:586 arg1 contents 552:559 contents 552:559 contents of ferulated arabinoxylans 552:586 Results showed that contents of ferulated arabinoxylans were 8.1 ± 0.04% and 6.8 ± 0.02 in NMB and NNMB, respectively. 36359985 1 8 theme bioactive 206:214 arg1 compounds 216:224 various bioactive compounds 198:224 various bioactive compounds 198:224 Maize bran is a good source of non-starch polysaccharides, having various bioactive compounds. 36359985 10 9 with state 1490:1494 arg1 regions 1519:1525 small crystalline regions 1501:1525 small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks) 1501:1606 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 8 10 theme visible 1207:1213 arg1 morphology 1240:1249 visible rough and porous surface morphology 1207:1249 visible rough and porous surface morphology 1207:1249 Moreover, SEM micrographs of ferulated arabinoxylans had visible rough and porous surface morphology. 36359985 10 11 theme small 1501:1505 arg1 regions 1519:1525 small crystalline regions 1501:1525 small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks) 1501:1606 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 5 12 theme ferulated 776:784 arg1 arabinoxylans 786:798 ferulated arabinoxylans 776:798 ferulated arabinoxylans 776:798 Furthermore, ferulated arabinoxylans have higher arabinose, xylose and ferulic acid contents. 36359985 6 13 theme arabinoxylans 896:908 arg1 spectra 862:868 FTIR spectra 857:868 FTIR spectra of NMB and NNMB ferulated arabinoxylans 857:908 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 8 14 theme SEM 1160:1162 arg1 micrographs 1164:1174 SEM micrographs 1160:1174 SEM micrographs of ferulated arabinoxylans 1160:1201 Moreover, SEM micrographs of ferulated arabinoxylans had visible rough and porous surface morphology. 36359985 6 15 theme NNMB 881:884 arg1 arabinoxylans 896:908 NMB and NNMB ferulated arabinoxylans 873:908 NMB and NNMB ferulated arabinoxylans 873:908 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 8 16 theme surface 1232:1238 arg1 morphology 1240:1249 visible rough and porous surface morphology 1207:1249 visible rough and porous surface morphology 1207:1249 Moreover, SEM micrographs of ferulated arabinoxylans had visible rough and porous surface morphology. 36359985 2 17 theme current 234:240 arg1 research 242:249 the current research 230:249 the current research 230:249 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 6 18 theme NMB 873:875 arg1 arabinoxylans 896:908 NMB and NNMB ferulated arabinoxylans 873:908 NMB and NNMB ferulated arabinoxylans 873:908 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 2 19 theme ferulated 269:277 arg1 arabinoxylans 279:291 the ferulated arabinoxylans 265:291 the ferulated arabinoxylans 265:291 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 1 20 theme good 148:151 arg1 bran 138:141 Maize bran 132:141 Maize bran 132:141 Maize bran is a good source of non-starch polysaccharides, having various bioactive compounds. 36359985 1 20 theme good 148:151 arg1 source 153:158 a good source 146:158 a good source of non-starch polysaccharides 146:188 Maize bran is a good source of non-starch polysaccharides, having various bioactive compounds. 36359985 0 21 theme Structural 16:25 arg1 Characterization 27:42 Biochemical and Structural Characterization 0:42 Biochemical and Structural Characterization of Ferulated Arabinoxylans 0:69 Biochemical and Structural Characterization of Ferulated Arabinoxylans Extracted from Nixtamalized and Non-Nixtamalized Maize Bran. 36359985 5 22 theme ferulic 834:840 arg1 contents 847:854 ferulic acid contents 834:854 ferulic acid contents 834:854 Furthermore, ferulated arabinoxylans have higher arabinose, xylose and ferulic acid contents. 36359985 4 23 from % 720:720 arg1 arabinoxylans 748:760 NMB and NNMB ferulated arabinoxylans 725:760 NMB and NNMB ferulated arabinoxylans 725:760 Moreover, the purity of arabinoxylans was 60.1 ± 0.8% and 57.04 ± 0.7% in NMB and NNMB ferulated arabinoxylans. 36359985 1 24 theme polysaccharides 174:188 arg1 bran 138:141 Maize bran 132:141 Maize bran 132:141 Maize bran is a good source of non-starch polysaccharides, having various bioactive compounds. 36359985 1 24 theme polysaccharides 174:188 arg1 source 153:158 a good source 146:158 a good source of non-starch polysaccharides 146:188 Maize bran is a good source of non-starch polysaccharides, having various bioactive compounds. 36359985 6 25 theme compounds 950:958 arg1 presence 923:930 the presence 919:930 the presence of polysaccharide compounds 919:958 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 7 26 dep cm-1 1117:1120 arg1 to 1122:1123 to 1122:1123 to 1122:1123 In addition, absorbance regions of arabinoxylans between 900 cm-1 to 1200 cm-1 were observed. 36359985 4 27 theme ± 715:715 arg1 % 720:720 57.04 ± 0.7% 709:720 57.04 ± 0.7% 709:720 Moreover, the purity of arabinoxylans was 60.1 ± 0.8% and 57.04 ± 0.7% in NMB and NNMB ferulated arabinoxylans. 36359985 0 28 theme Maize 120:124 arg1 Bran 126:129 Nixtamalized and Non-Nixtamalized Maize Bran 86:129 Nixtamalized and Non-Nixtamalized Maize Bran 86:129 Biochemical and Structural Characterization of Ferulated Arabinoxylans Extracted from Nixtamalized and Non-Nixtamalized Maize Bran. 36359985 2 29 theme phenolic 428:435 arg1 monosaccharides 411:425 monosaccharides 411:425 monosaccharides 411:425 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 29 theme phenolic 428:435 arg1 compounds 437:445 phenolic compounds 428:445 phenolic compounds 428:445 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 9 30 theme ferulated 1261:1269 arg1 arabinoxylans 1271:1283 ferulated arabinoxylans 1261:1283 ferulated arabinoxylans of NMB and NNMB 1261:1299 Further, ferulated arabinoxylans of NMB and NNMB did not exhibit any sharp peaks in XRD graphs, attributed to their amorphous nature. 36359985 10 31 contain has 1473:1475 arg1 material 1464:1471 the material 1460:1471 the material 1460:1471 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 10 31 contain has 1473:1475 arg2 state 1490:1494 an amorphous state 1477:1494 an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks) 1477:1606 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 3 32 from ± 613:613 arg1 NMB 623:625 NMB 623:625 NMB 623:625 Results showed that contents of ferulated arabinoxylans were 8.1 ± 0.04% and 6.8 ± 0.02 in NMB and NNMB, respectively. 36359985 3 32 from ± 613:613 arg1 NNMB 631:634 NNMB 631:634 NNMB 631:634 Results showed that contents of ferulated arabinoxylans were 8.1 ± 0.04% and 6.8 ± 0.02 in NMB and NNMB, respectively. 36359985 2 33 theme biochemical 386:396 arg1 composition 398:408 their biochemical composition 380:408 their biochemical composition (monosaccharides, phenolic compounds) 380:446 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 0 34 theme Biochemical 0:10 arg1 Characterization 27:42 Biochemical and Structural Characterization 0:42 Biochemical and Structural Characterization of Ferulated Arabinoxylans 0:69 Biochemical and Structural Characterization of Ferulated Arabinoxylans Extracted from Nixtamalized and Non-Nixtamalized Maize Bran. 36359985 7 35 theme 900 1113:1115 arg1 cm-1 1117:1120 cm-1 1117:1120 cm-1 1117:1120 In addition, absorbance regions of arabinoxylans between 900 cm-1 to 1200 cm-1 were observed. 36359985 1 36 theme Maize 132:136 arg1 bran 138:141 Maize bran 132:141 Maize bran 132:141 Maize bran is a good source of non-starch polysaccharides, having various bioactive compounds. 36359985 1 36 theme Maize 132:136 arg1 source 153:158 a good source 146:158 a good source of non-starch polysaccharides 146:188 Maize bran is a good source of non-starch polysaccharides, having various bioactive compounds. 36359985 7 37 theme arabinoxylans 1091:1103 arg1 regions 1080:1086 absorbance regions 1069:1086 absorbance regions of arabinoxylans between 900 cm-1 to 1200 cm-1 1069:1133 In addition, absorbance regions of arabinoxylans between 900 cm-1 to 1200 cm-1 were observed. 36359985 6 38 theme corresponding 968:980 arg1 band 982:985 the corresponding band 964:985 the corresponding band 964:985 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 5 39 dep higher 805:810 arg1 arabinose 812:820 arabinose 812:820 arabinose 812:820 Furthermore, ferulated arabinoxylans have higher arabinose, xylose and ferulic acid contents. 36359985 5 39 dep higher 805:810 arg1 contents 847:854 ferulic acid contents 834:854 ferulic acid contents 834:854 Furthermore, ferulated arabinoxylans have higher arabinose, xylose and ferulic acid contents. 36359985 5 39 dep higher 805:810 arg1 xylose 823:828 xylose 823:828 xylose 823:828 Furthermore, ferulated arabinoxylans have higher arabinose, xylose and ferulic acid contents. 36359985 0 40 theme Arabinoxylans 57:69 arg1 Characterization 27:42 Biochemical and Structural Characterization 0:42 Biochemical and Structural Characterization of Ferulated Arabinoxylans 0:69 Biochemical and Structural Characterization of Ferulated Arabinoxylans Extracted from Nixtamalized and Non-Nixtamalized Maize Bran. 36359985 4 41 theme NMB 725:727 arg1 arabinoxylans 748:760 NMB and NNMB ferulated arabinoxylans 725:760 NMB and NNMB ferulated arabinoxylans 725:760 Moreover, the purity of arabinoxylans was 60.1 ± 0.8% and 57.04 ± 0.7% in NMB and NNMB ferulated arabinoxylans. 36359985 2 42 theme maize 349:353 arg1 bran 355:358 non-nixtamalized maize bran 332:358 non-nixtamalized maize bran (NNMB) 332:365 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 42 theme maize 349:353 arg1 NNMB 361:364 NNMB 361:364 NNMB 361:364 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 9 43 theme sharp 1321:1325 arg1 peaks 1327:1331 any sharp peaks 1317:1331 any sharp peaks in XRD graphs 1317:1345 Further, ferulated arabinoxylans of NMB and NNMB did not exhibit any sharp peaks in XRD graphs, attributed to their amorphous nature. 36359985 9 44 from peaks 1327:1331 arg1 graphs 1340:1345 XRD graphs 1336:1345 XRD graphs 1336:1345 Further, ferulated arabinoxylans of NMB and NNMB did not exhibit any sharp peaks in XRD graphs, attributed to their amorphous nature. 36359985 4 45 theme NNMB 733:736 arg1 arabinoxylans 748:760 NMB and NNMB ferulated arabinoxylans 725:760 NMB and NNMB ferulated arabinoxylans 725:760 Moreover, the purity of arabinoxylans was 60.1 ± 0.8% and 57.04 ± 0.7% in NMB and NNMB ferulated arabinoxylans. 36359985 6 46 theme bond 1040:1043 arg1 vibration 1045:1053 glycosidic bond vibration 1029:1053 glycosidic bond vibration 1029:1053 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 6 47 theme FTIR 857:860 arg1 spectra 862:868 FTIR spectra 857:868 FTIR spectra of NMB and NNMB ferulated arabinoxylans 857:908 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 5 48 theme acid 842:845 arg1 contents 847:854 ferulic acid contents 834:854 ferulic acid contents 834:854 Furthermore, ferulated arabinoxylans have higher arabinose, xylose and ferulic acid contents. 36359985 10 49 theme amorphous 1480:1488 arg1 state 1490:1494 an amorphous state 1477:1494 an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks) 1477:1606 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 2 50 theme nixtamalized 298:309 arg1 NMB 323:325 NMB 323:325 NMB 323:325 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 50 theme nixtamalized 298:309 arg1 bran 317:320 nixtamalized maize bran 298:320 nixtamalized maize bran (NMB) 298:326 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 3 51 theme ferulated 564:572 arg1 arabinoxylans 574:586 ferulated arabinoxylans 564:586 ferulated arabinoxylans 564:586 Results showed that contents of ferulated arabinoxylans were 8.1 ± 0.04% and 6.8 ± 0.02 in NMB and NNMB, respectively. 36359985 1 52 theme various 198:204 arg1 compounds 216:224 various bioactive compounds 198:224 various bioactive compounds 198:224 Maize bran is a good source of non-starch polysaccharides, having various bioactive compounds. 36359985 8 53 theme ferulated 1179:1187 arg1 arabinoxylans 1189:1201 ferulated arabinoxylans 1179:1201 ferulated arabinoxylans 1179:1201 Moreover, SEM micrographs of ferulated arabinoxylans had visible rough and porous surface morphology. 36359985 10 54 theme crystalline 1507:1517 arg1 regions 1519:1525 small crystalline regions 1501:1525 small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks) 1501:1606 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 3 55 theme ± 597:597 arg1 % 603:603 8.1 ± 0.04% 593:603 8.1 ± 0.04% 593:603 Results showed that contents of ferulated arabinoxylans were 8.1 ± 0.04% and 6.8 ± 0.02 in NMB and NNMB, respectively. 36359985 6 56 theme ferulated 886:894 arg1 arabinoxylans 896:908 NMB and NNMB ferulated arabinoxylans 873:908 NMB and NNMB ferulated arabinoxylans 873:908 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 8 57 theme rough 1215:1219 arg1 morphology 1240:1249 visible rough and porous surface morphology 1207:1249 visible rough and porous surface morphology 1207:1249 Moreover, SEM micrographs of ferulated arabinoxylans had visible rough and porous surface morphology. 36359985 8 58 theme porous 1225:1230 arg1 morphology 1240:1249 visible rough and porous surface morphology 1207:1249 visible rough and porous surface morphology 1207:1249 Moreover, SEM micrographs of ferulated arabinoxylans had visible rough and porous surface morphology. 36359985 10 59 theme sharp 1595:1599 arg1 peaks 1601:1605 small and narrow sharp peaks 1578:1605 small and narrow sharp peaks 1578:1605 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 10 59 theme sharp 1595:1599 arg1 xylans 1570:1575 xylans 1570:1575 xylans (small and narrow sharp peaks) 1570:1606 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 0 60 theme Nixtamalized 86:97 arg1 Bran 126:129 Nixtamalized and Non-Nixtamalized Maize Bran 86:129 Nixtamalized and Non-Nixtamalized Maize Bran 86:129 Biochemical and Structural Characterization of Ferulated Arabinoxylans Extracted from Nixtamalized and Non-Nixtamalized Maize Bran. 36359985 10 61 from 20.0° 1418:1422 arg1 peaks 1409:1413 peaks 1409:1413 peaks 1409:1413 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 0 62 theme Non-Nixtamalized 103:118 arg1 Bran 126:129 Nixtamalized and Non-Nixtamalized Maize Bran 86:129 Nixtamalized and Non-Nixtamalized Maize Bran 86:129 Biochemical and Structural Characterization of Ferulated Arabinoxylans Extracted from Nixtamalized and Non-Nixtamalized Maize Bran. 36359985 1 63 theme non-starch 163:172 arg1 polysaccharides 174:188 non-starch polysaccharides 163:188 non-starch polysaccharides 163:188 Maize bran is a good source of non-starch polysaccharides, having various bioactive compounds. 36359985 6 64 located observed 991:998 arg1 cm-1 1007:1010 993 cm-1 1003:1010 993 cm-1 1003:1010 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 6 64 located observed 991:998 arg2 band 982:985 the corresponding band 964:985 the corresponding band 964:985 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 6 65 theme polysaccharide 935:948 arg1 compounds 950:958 polysaccharide compounds 935:958 polysaccharide compounds 935:958 FTIR spectra of NMB and NNMB ferulated arabinoxylans depicted the presence of polysaccharide compounds and the corresponding band was observed at 993 cm-1, which is due to glycosidic bond vibration. 36359985 2 66 theme antioxidant 510:520 arg1 activity 522:529 antioxidant activity 510:529 antioxidant activity 510:529 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 9 67 dep exhibit 1309:1315 arg1 attributed 1348:1357 attributed 1348:1357 attributed to their amorphous nature 1348:1383 Further, ferulated arabinoxylans of NMB and NNMB did not exhibit any sharp peaks in XRD graphs, attributed to their amorphous nature. 36359985 3 68 from % 603:603 arg1 NMB 623:625 NMB 623:625 NMB 623:625 Results showed that contents of ferulated arabinoxylans were 8.1 ± 0.04% and 6.8 ± 0.02 in NMB and NNMB, respectively. 36359985 3 68 from % 603:603 arg1 NNMB 631:634 NNMB 631:634 NNMB 631:634 Results showed that contents of ferulated arabinoxylans were 8.1 ± 0.04% and 6.8 ± 0.02 in NMB and NNMB, respectively. 36359985 10 69 theme narrow 1588:1593 arg1 peaks 1601:1605 small and narrow sharp peaks 1578:1605 small and narrow sharp peaks 1578:1605 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 10 69 theme narrow 1588:1593 arg1 xylans 1570:1575 xylans 1570:1575 xylans (small and narrow sharp peaks) 1570:1606 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 7 70 theme 1200 1125:1128 arg1 cm-1 1117:1120 cm-1 1117:1120 cm-1 1117:1120 In addition, absorbance regions of arabinoxylans between 900 cm-1 to 1200 cm-1 were observed. 36359985 10 71 theme XRD 1395:1397 arg1 2θ 1399:1400 XRD 2θ 1395:1400 XRD 2θ 1395:1400 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 5 72 contain have 800:803 arg1 arabinoxylans 786:798 ferulated arabinoxylans 776:798 ferulated arabinoxylans 776:798 Furthermore, ferulated arabinoxylans have higher arabinose, xylose and ferulic acid contents. 36359985 5 72 contain have 800:803 arg2 higher 805:810 higher 805:810 higher 805:810 Furthermore, ferulated arabinoxylans have higher arabinose, xylose and ferulic acid contents. 36359985 2 73 dep characteristics 463:477 arg1 FTIR 480:483 FTIR 480:483 FTIR 480:483 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 73 dep characteristics 463:477 arg1 characteristics 463:477 structural characteristics 452:477 structural characteristics (FTIR, SEM and XRD) 452:497 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 73 dep characteristics 463:477 arg1 XRD 494:496 XRD 494:496 XRD 494:496 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 73 dep characteristics 463:477 arg1 SEM 486:488 SEM 486:488 SEM 486:488 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 4 74 from % 703:703 arg1 arabinoxylans 748:760 NMB and NNMB ferulated arabinoxylans 725:760 NMB and NNMB ferulated arabinoxylans 725:760 Moreover, the purity of arabinoxylans was 60.1 ± 0.8% and 57.04 ± 0.7% in NMB and NNMB ferulated arabinoxylans. 36359985 2 75 theme structural 452:461 arg1 FTIR 480:483 FTIR 480:483 FTIR 480:483 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 75 theme structural 452:461 arg1 characteristics 463:477 structural characteristics 452:477 structural characteristics (FTIR, SEM and XRD) 452:497 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 75 theme structural 452:461 arg1 XRD 494:496 XRD 494:496 XRD 494:496 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 75 theme structural 452:461 arg1 SEM 486:488 SEM 486:488 SEM 486:488 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 4 76 theme ± 698:698 arg1 % 703:703 60.1 ± 0.8% 693:703 60.1 ± 0.8% 693:703 Moreover, the purity of arabinoxylans was 60.1 ± 0.8% and 57.04 ± 0.7% in NMB and NNMB ferulated arabinoxylans. 36359985 4 76 theme ± 698:698 arg1 purity 665:670 the purity 661:670 the purity of arabinoxylans 661:687 Moreover, the purity of arabinoxylans was 60.1 ± 0.8% and 57.04 ± 0.7% in NMB and NNMB ferulated arabinoxylans. 36359985 9 77 theme NMB 1288:1290 arg1 arabinoxylans 1271:1283 ferulated arabinoxylans 1261:1283 ferulated arabinoxylans of NMB and NNMB 1261:1299 Further, ferulated arabinoxylans of NMB and NNMB did not exhibit any sharp peaks in XRD graphs, attributed to their amorphous nature. 36359985 10 78 theme small 1578:1582 arg1 peaks 1601:1605 small and narrow sharp peaks 1578:1605 small and narrow sharp peaks 1578:1605 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 10 78 theme small 1578:1582 arg1 xylans 1570:1575 xylans 1570:1575 xylans (small and narrow sharp peaks) 1570:1606 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 0 79 theme Ferulated 47:55 arg1 Arabinoxylans 57:69 Ferulated Arabinoxylans 47:69 Ferulated Arabinoxylans 47:69 Biochemical and Structural Characterization of Ferulated Arabinoxylans Extracted from Nixtamalized and Non-Nixtamalized Maize Bran. 36359985 9 80 theme NNMB 1296:1299 arg1 arabinoxylans 1271:1283 ferulated arabinoxylans 1261:1283 ferulated arabinoxylans of NMB and NNMB 1261:1299 Further, ferulated arabinoxylans of NMB and NNMB did not exhibit any sharp peaks in XRD graphs, attributed to their amorphous nature. 36359985 4 81 theme ferulated 738:746 arg1 arabinoxylans 748:760 NMB and NNMB ferulated arabinoxylans 725:760 NMB and NNMB ferulated arabinoxylans 725:760 Moreover, the purity of arabinoxylans was 60.1 ± 0.8% and 57.04 ± 0.7% in NMB and NNMB ferulated arabinoxylans. 36359985 7 82 located observed 1140:1147 arg1 addition 1059:1066 addition 1059:1066 addition 1059:1066 In addition, absorbance regions of arabinoxylans between 900 cm-1 to 1200 cm-1 were observed. 36359985 7 82 located observed 1140:1147 arg2 regions 1080:1086 absorbance regions 1069:1086 absorbance regions of arabinoxylans between 900 cm-1 to 1200 cm-1 1069:1133 In addition, absorbance regions of arabinoxylans between 900 cm-1 to 1200 cm-1 were observed. 36359985 10 83 theme xylans 1570:1575 arg1 presence 1558:1565 the presence 1554:1565 the presence of xylans (small and narrow sharp peaks) 1554:1606 However, XRD 2θ showed peaks at 20.0°, which predominantly indicated that the material has an amorphous state with small crystalline regions in the sample, which shows the presence of xylans (small and narrow sharp peaks). 36359985 7 84 theme absorbance 1069:1078 arg1 regions 1080:1086 absorbance regions 1069:1086 absorbance regions of arabinoxylans between 900 cm-1 to 1200 cm-1 1069:1133 In addition, absorbance regions of arabinoxylans between 900 cm-1 to 1200 cm-1 were observed. 36359985 2 85 theme non-nixtamalized 332:347 arg1 bran 355:358 non-nixtamalized maize bran 332:358 non-nixtamalized maize bran (NNMB) 332:365 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 85 theme non-nixtamalized 332:347 arg1 NNMB 361:364 NNMB 361:364 NNMB 361:364 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 86 dep composition 398:408 arg1 monosaccharides 411:425 monosaccharides 411:425 monosaccharides 411:425 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 2 86 dep composition 398:408 arg1 compounds 437:445 phenolic compounds 428:445 phenolic compounds 428:445 In the current research, we extracted the ferulated arabinoxylans from nixtamalized maize bran (NMB) and non-nixtamalized maize bran (NNMB) and explored their biochemical composition (monosaccharides, phenolic compounds) and structural characteristics (FTIR, SEM and XRD) as well as antioxidant activity. 36359985 9 87 theme XRD 1336:1338 arg1 graphs 1340:1345 XRD graphs 1336:1345 XRD graphs 1336:1345 Further, ferulated arabinoxylans of NMB and NNMB did not exhibit any sharp peaks in XRD graphs, attributed to their amorphous nature. 36781270 0 0 from impact 18:23 arg1 browning 38:45 browning 38:45 browning of polyphenol oxidation system in thermal and storage processing 38:110 Understanding the impact of pectin on browning of polyphenol oxidation system in thermal and storage processing. 36781270 7 1 theme pectin 1149:1154 arg1 composition 1045:1055 the monosaccharide composition 1026:1055 the monosaccharide composition 1026:1055 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 1 theme pectin 1149:1154 arg1 Ratio 1076:1080 Ratio 3 1076:1082 Ratio 3 1076:1082 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 1 theme pectin 1149:1154 arg1 ζ-potential 1108:1118 ζ-potential 1108:1118 ζ-potential 1108:1118 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 1 theme pectin 1149:1154 arg1 Ratio 1058:1062 Ratio 1 1058:1064 Ratio 1 1058:1064 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 1 theme pectin 1149:1154 arg1 Ratio 1067:1071 Ratio 2 1067:1073 Ratio 2 1067:1073 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 1 theme pectin 1149:1154 arg1 esterification 1092:1105 methyl esterification 1085:1105 methyl esterification 1085:1105 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 1 theme pectin 1149:1154 arg1 index 1140:1144 polydispersity index 1125:1144 polydispersity index 1125:1144 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 2 theme monosaccharide 1030:1043 arg1 composition 1045:1055 the monosaccharide composition 1026:1055 the monosaccharide composition 1026:1055 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 2 theme monosaccharide 1030:1043 arg1 Ratio 1076:1080 Ratio 3 1076:1082 Ratio 3 1076:1082 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 2 theme monosaccharide 1030:1043 arg1 ζ-potential 1108:1118 ζ-potential 1108:1118 ζ-potential 1108:1118 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 2 theme monosaccharide 1030:1043 arg1 Ratio 1058:1062 Ratio 1 1058:1064 Ratio 1 1058:1064 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 2 theme monosaccharide 1030:1043 arg1 Ratio 1067:1071 Ratio 2 1067:1073 Ratio 2 1067:1073 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 2 theme monosaccharide 1030:1043 arg1 esterification 1092:1105 methyl esterification 1085:1105 methyl esterification 1085:1105 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 2 theme monosaccharide 1030:1043 arg1 index 1140:1144 polydispersity index 1125:1144 polydispersity index 1125:1144 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 1 3 theme products 146:153 arg1 Browning 113:120 Browning 113:120 Browning of some processed fruit products 113:153 Browning of some processed fruit products was affected not only by polyphenol oxidation but also by cell wall polysaccharides (pectin). 36781270 0 4 theme system 71:76 arg1 browning 38:45 browning 38:45 browning of polyphenol oxidation system in thermal and storage processing 38:110 Understanding the impact of pectin on browning of polyphenol oxidation system in thermal and storage processing. 36781270 4 5 theme structural 530:539 arg1 properties 561:570 the structural and physicochemical properties 526:570 the structural and physicochemical properties of pectin 526:580 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 2 6 theme pectin 320:325 arg1 system 327:332 the pectin system 316:332 the pectin system 316:332 The study was performed to understand the mechanism of browning in the pectin system. 36781270 2 7 from mechanism 291:299 arg1 system 327:332 the pectin system 316:332 the pectin system 316:332 The study was performed to understand the mechanism of browning in the pectin system. 36781270 5 8 theme polyphenols 762:772 arg1 characteristics 743:757 the fluorescence characteristics 726:757 the fluorescence characteristics of polyphenols 726:772 Moreover, pectin impacted the fluorescence characteristics of polyphenols by cross-linking with the aromatic ring of polyphenols. 36781270 4 9 from effects 613:619 arg1 kinetics 628:635 the kinetics 624:635 the kinetics of polyphenol oxidation 624:659 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 4 9 from effects 613:619 arg1 stability 669:677 the stability 665:677 the stability of free polyphenols 665:697 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 5 10 theme fluorescence 730:741 arg1 characteristics 743:757 the fluorescence characteristics 726:757 the fluorescence characteristics of polyphenols 726:772 Moreover, pectin impacted the fluorescence characteristics of polyphenols by cross-linking with the aromatic ring of polyphenols. 36781270 7 11 theme correlation 991:1001 arg1 analysis 1003:1010 The correlation analysis 987:1010 The correlation analysis 987:1010 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 12 theme oxidation 1229:1237 arg1 system 1239:1244 the pectin-polyphenol oxidation system 1207:1244 the pectin-polyphenol oxidation system 1207:1244 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 0 13 from browning 38:45 arg1 thermal 81:87 thermal 81:87 thermal 81:87 Understanding the impact of pectin on browning of polyphenol oxidation system in thermal and storage processing. 36781270 0 13 from browning 38:45 arg1 processing 101:110 storage processing 93:110 storage processing 93:110 Understanding the impact of pectin on browning of polyphenol oxidation system in thermal and storage processing. 36781270 4 14 theme oxidation 651:659 arg1 kinetics 628:635 the kinetics 624:635 the kinetics of polyphenol oxidation 624:659 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 4 14 theme oxidation 651:659 arg1 stability 669:677 the stability 665:677 the stability of free polyphenols 665:697 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 4 15 theme free 682:685 arg1 polyphenols 687:697 free polyphenols 682:697 free polyphenols 682:697 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 0 16 theme storage 93:99 arg1 processing 101:110 storage processing 93:110 storage processing 93:110 Understanding the impact of pectin on browning of polyphenol oxidation system in thermal and storage processing. 36781270 6 17 theme pectin 926:931 arg1 vibration 913:921 the chemical bond vibration 895:921 the chemical bond vibration of pectin 895:931 In turn, the interaction between polyphenols and pectin impacted the chemical bond vibration of pectin, thereby affecting its optical features and browning. 36781270 7 18 theme polydispersity 1125:1138 arg1 composition 1045:1055 the monosaccharide composition 1026:1055 the monosaccharide composition 1026:1055 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 18 theme polydispersity 1125:1138 arg1 index 1140:1144 polydispersity index 1125:1144 polydispersity index 1125:1144 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 3 19 theme oxidation 365:373 arg1 system 375:380 The catechin/chlorogenic acid oxidation system 335:380 The catechin/chlorogenic acid oxidation system in three pectins 335:397 The catechin/chlorogenic acid oxidation system in three pectins significantly enhanced their browning during thermal storage with pectin structure- and concentration-dependent. 36781270 3 20 from system 375:380 arg1 pectins 391:397 three pectins 385:397 three pectins 385:397 The catechin/chlorogenic acid oxidation system in three pectins significantly enhanced their browning during thermal storage with pectin structure- and concentration-dependent. 36781270 7 21 theme pectin-polyphenol 1211:1227 arg1 system 1239:1244 the pectin-polyphenol oxidation system 1207:1244 the pectin-polyphenol oxidation system 1207:1244 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 4 22 theme polyphenols 687:697 arg1 kinetics 628:635 the kinetics 624:635 the kinetics of polyphenol oxidation 624:659 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 4 22 theme polyphenols 687:697 arg1 stability 669:677 the stability 665:677 the stability of free polyphenols 665:697 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 3 23 theme catechin/chlorogenic 339:358 arg1 system 375:380 The catechin/chlorogenic acid oxidation system 335:380 The catechin/chlorogenic acid oxidation system in three pectins 335:397 The catechin/chlorogenic acid oxidation system in three pectins significantly enhanced their browning during thermal storage with pectin structure- and concentration-dependent. 36781270 4 24 theme pectin 575:580 arg1 properties 561:570 the structural and physicochemical properties 526:570 the structural and physicochemical properties of pectin 526:580 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 1 25 theme polyphenol 180:189 arg1 oxidation 191:199 polyphenol oxidation 180:199 polyphenol oxidation 180:199 Browning of some processed fruit products was affected not only by polyphenol oxidation but also by cell wall polysaccharides (pectin). 36781270 3 26 theme acid 360:363 arg1 system 375:380 The catechin/chlorogenic acid oxidation system 335:380 The catechin/chlorogenic acid oxidation system in three pectins 335:397 The catechin/chlorogenic acid oxidation system in three pectins significantly enhanced their browning during thermal storage with pectin structure- and concentration-dependent. 36781270 3 27 with storage 452:458 arg1 concentration-dependent 487:509 concentration-dependent 487:509 concentration-dependent 487:509 The catechin/chlorogenic acid oxidation system in three pectins significantly enhanced their browning during thermal storage with pectin structure- and concentration-dependent. 36781270 3 27 with storage 452:458 arg1 structure- 472:481 pectin structure- 465:481 pectin structure- 465:481 The catechin/chlorogenic acid oxidation system in three pectins significantly enhanced their browning during thermal storage with pectin structure- and concentration-dependent. 36781270 6 28 theme optical 956:962 arg1 features 964:971 its optical features 952:971 its optical features 952:971 In turn, the interaction between polyphenols and pectin impacted the chemical bond vibration of pectin, thereby affecting its optical features and browning. 36781270 3 29 theme pectin 465:470 arg1 structure- 472:481 pectin structure- 465:481 pectin structure- 465:481 The catechin/chlorogenic acid oxidation system in three pectins significantly enhanced their browning during thermal storage with pectin structure- and concentration-dependent. 36781270 5 30 theme polyphenols 817:827 arg1 ring 809:812 the aromatic ring 796:812 the aromatic ring of polyphenols 796:827 Moreover, pectin impacted the fluorescence characteristics of polyphenols by cross-linking with the aromatic ring of polyphenols. 36781270 6 31 theme bond 908:911 arg1 vibration 913:921 the chemical bond vibration 895:921 the chemical bond vibration of pectin 895:931 In turn, the interaction between polyphenols and pectin impacted the chemical bond vibration of pectin, thereby affecting its optical features and browning. 36781270 3 32 theme thermal 444:450 arg1 storage 452:458 thermal storage 444:458 thermal storage with pectin structure- and concentration-dependent 444:509 The catechin/chlorogenic acid oxidation system in three pectins significantly enhanced their browning during thermal storage with pectin structure- and concentration-dependent. 36781270 0 33 theme pectin 28:33 arg1 impact 18:23 the impact 14:23 the impact of pectin on browning of polyphenol oxidation system in thermal and storage processing 14:110 Understanding the impact of pectin on browning of polyphenol oxidation system in thermal and storage processing. 36781270 4 34 theme physicochemical 545:559 arg1 properties 561:570 the structural and physicochemical properties 526:570 the structural and physicochemical properties of pectin 526:580 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 7 35 theme methyl 1085:1090 arg1 composition 1045:1055 the monosaccharide composition 1026:1055 the monosaccharide composition 1026:1055 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 7 35 theme methyl 1085:1090 arg1 esterification 1092:1105 methyl esterification 1085:1105 methyl esterification 1085:1105 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 6 36 theme chemical 899:906 arg1 vibration 913:921 the chemical bond vibration 895:921 the chemical bond vibration of pectin 895:931 In turn, the interaction between polyphenols and pectin impacted the chemical bond vibration of pectin, thereby affecting its optical features and browning. 36781270 4 37 theme polyphenol 640:649 arg1 oxidation 651:659 polyphenol oxidation 640:659 polyphenol oxidation 640:659 Particularly, the structural and physicochemical properties of pectin were examined to determine its effects on the kinetics of polyphenol oxidation and the stability of free polyphenols. 36781270 7 38 theme system 1239:1244 arg1 browning 1195:1202 the browning 1191:1202 the browning of the pectin-polyphenol oxidation system 1191:1244 The correlation analysis revealed that the monosaccharide composition, Ratio 1, Ratio 2, Ratio 3, methyl esterification, ζ-potential, and polydispersity index of pectin were significantly correlated with the browning of the pectin-polyphenol oxidation system. 36781270 5 39 theme aromatic 800:807 arg1 ring 809:812 the aromatic ring 796:812 the aromatic ring of polyphenols 796:827 Moreover, pectin impacted the fluorescence characteristics of polyphenols by cross-linking with the aromatic ring of polyphenols. 36781270 2 40 theme browning 304:311 arg1 mechanism 291:299 the mechanism 287:299 the mechanism of browning in the pectin system 287:332 The study was performed to understand the mechanism of browning in the pectin system. 36781270 1 41 theme cell 213:216 arg1 pectin 240:245 pectin 240:245 pectin 240:245 Browning of some processed fruit products was affected not only by polyphenol oxidation but also by cell wall polysaccharides (pectin). 36781270 1 41 theme cell 213:216 arg1 polysaccharides 223:237 cell wall polysaccharides 213:237 cell wall polysaccharides (pectin) 213:246 Browning of some processed fruit products was affected not only by polyphenol oxidation but also by cell wall polysaccharides (pectin). 36781270 0 42 theme oxidation 61:69 arg1 system 71:76 polyphenol oxidation system 50:76 polyphenol oxidation system 50:76 Understanding the impact of pectin on browning of polyphenol oxidation system in thermal and storage processing. 36781270 1 43 theme processed 130:138 arg1 products 146:153 some processed fruit products 125:153 some processed fruit products 125:153 Browning of some processed fruit products was affected not only by polyphenol oxidation but also by cell wall polysaccharides (pectin). 36781270 1 44 theme wall 218:221 arg1 pectin 240:245 pectin 240:245 pectin 240:245 Browning of some processed fruit products was affected not only by polyphenol oxidation but also by cell wall polysaccharides (pectin). 36781270 1 44 theme wall 218:221 arg1 polysaccharides 223:237 cell wall polysaccharides 213:237 cell wall polysaccharides (pectin) 213:246 Browning of some processed fruit products was affected not only by polyphenol oxidation but also by cell wall polysaccharides (pectin). 36781270 0 45 theme polyphenol 50:59 arg1 system 71:76 polyphenol oxidation system 50:76 polyphenol oxidation system 50:76 Understanding the impact of pectin on browning of polyphenol oxidation system in thermal and storage processing. 36781270 1 46 theme fruit 140:144 arg1 products 146:153 some processed fruit products 125:153 some processed fruit products 125:153 Browning of some processed fruit products was affected not only by polyphenol oxidation but also by cell wall polysaccharides (pectin). 36204299 2 0 theme intestinal 485:494 arg1 microbes 496:503 intestinal microbes 485:503 intestinal microbes 485:503 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 5 1 from changes 842:848 arg1 flora 877:881 the dominant intestinal flora 853:881 the dominant intestinal flora of female rats 853:896 At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. 36204299 4 2 theme intestinal 700:709 arg1 flora 711:715 the intestinal flora 696:715 the intestinal flora of male and female rats 696:739 In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. 36204299 0 3 theme intestinal 81:90 arg1 microorganisms 92:105 intestinal microorganisms 81:105 intestinal microorganisms 81:105 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 0 4 from differences 15:25 arg1 microorganisms 92:105 intestinal microorganisms 81:105 intestinal microorganisms 81:105 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 0 4 from differences 15:25 arg1 rats 113:116 SD rats 110:116 SD rats 110:116 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 0 4 from differences 15:25 arg1 effects 34:40 the effects 30:40 the effects of Inonotus obliquus polysaccharide on intestinal microorganisms 30:105 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 8 5 from effects 1518:1524 arg1 composition 1560:1570 the composition 1556:1570 the composition of the intestinal microbiota 1556:1599 These results help to understand the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases. 36204299 8 5 from effects 1518:1524 arg1 diseases 1615:1622 diseases 1615:1622 diseases 1615:1622 These results help to understand the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases. 36204299 1 6 theme research 170:177 arg1 value 195:199 research and application value 170:199 research and application value for the prevention of diseases 170:230 Natural edible fungal polysaccharides are of research and application value for the prevention of diseases by improving the microenvironment within the intestine. 36204299 6 7 from families 1184:1191 arg1 proportion 1140:1149 an increasing proportion 1126:1149 an increasing proportion of Muribaculaceae from different families and genera 1126:1202 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 8 8 theme microbiota 1590:1599 arg1 composition 1560:1570 the composition 1556:1570 the composition of the intestinal microbiota 1556:1599 These results help to understand the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases. 36204299 0 9 theme SD 110:111 arg1 rats 113:116 SD rats 110:116 SD rats 110:116 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 7 10 theme microorganisms 1335:1348 arg1 vitality 1308:1315 the vitality 1304:1315 the vitality of their dominant microorganisms 1304:1348 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 36204299 5 11 theme intestinal 866:875 arg1 flora 877:881 the dominant intestinal flora 853:881 the dominant intestinal flora of female rats 853:896 At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. 36204299 7 12 theme intestinal 1236:1245 arg1 microenvironment 1247:1262 the intestinal microenvironment 1232:1262 the intestinal microenvironment of male and female SD rats 1232:1289 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 36204299 7 13 theme dominant 1401:1408 arg1 microflora 1410:1419 dominant microflora 1401:1419 dominant microflora that were conducive to the balance of the intestinal flora 1401:1478 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 36204299 2 14 theme polysaccharide 306:319 arg1 extracts 327:334 Inonotus obliquus polysaccharide (IOP) extracts 288:334 Inonotus obliquus polysaccharide (IOP) extracts 288:334 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 2 15 theme strong 341:346 arg1 activities 401:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 2 16 theme intestinal 515:524 arg1 homeostasis 526:536 intestinal homeostasis 515:536 intestinal homeostasis 515:536 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 2 17 used used 438:441 arg2 it 426:427 it 426:427 it 426:427 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 2 17 used used 438:441 arg2 prebiotics 446:455 prebiotics 446:455 prebiotics 446:455 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 2 17 used used 438:441 arg2 such 420:423 such 420:423 such 420:423 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 6 18 theme intestinal 1013:1022 arg1 Clostridia 955:964 Clostridia 955:964 Clostridia 955:964 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 6 18 theme intestinal 1013:1022 arg1 microbes 1024:1031 the dominant intestinal microbes 1000:1031 the dominant intestinal microbes in female rats 1000:1046 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 6 18 theme intestinal 1013:1022 arg1 Roseburia 985:993 Roseburia 985:993 Roseburia 985:993 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 6 18 theme intestinal 1013:1022 arg1 Lactobacillus 967:979 Lactobacillus 967:979 Lactobacillus 967:979 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 2 19 theme obliquus 297:304 arg1 polysaccharide 306:319 Inonotus obliquus polysaccharide 288:319 Inonotus obliquus polysaccharide (IOP) extracts 288:334 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 2 19 theme obliquus 297:304 arg1 IOP 322:324 IOP 322:324 IOP 322:324 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 6 20 theme female 1036:1041 arg1 rats 1043:1046 female rats 1036:1046 female rats 1036:1046 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 7 21 theme microflora 1410:1419 arg1 screening 1388:1396 the screening 1384:1396 the screening of dominant microflora that were conducive to the balance of the intestinal flora 1384:1478 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 36204299 6 22 theme different 1084:1092 arg1 families 1094:1101 different families 1084:1101 different families 1084:1101 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 7 23 theme rats 1286:1289 arg1 microenvironment 1247:1262 the intestinal microenvironment 1232:1262 the intestinal microenvironment of male and female SD rats 1232:1289 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 36204299 2 24 theme Inonotus 288:295 arg1 polysaccharide 306:319 Inonotus obliquus polysaccharide 288:319 Inonotus obliquus polysaccharide (IOP) extracts 288:334 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 2 24 theme Inonotus 288:295 arg1 IOP 322:324 IOP 322:324 IOP 322:324 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 1 25 theme application 183:193 arg1 value 195:199 research and application value 170:199 research and application value for the prevention of diseases 170:230 Natural edible fungal polysaccharides are of research and application value for the prevention of diseases by improving the microenvironment within the intestine. 36204299 0 26 from effects 34:40 arg1 microorganisms 92:105 intestinal microorganisms 81:105 intestinal microorganisms 81:105 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 4 27 theme rats 736:739 arg1 flora 711:715 the intestinal flora 696:715 the intestinal flora of male and female rats 696:739 In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. 36204299 4 28 theme different 675:683 arg1 effects 685:691 different effects 675:691 different effects 675:691 In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. 36204299 0 29 theme Gender-related 0:13 arg1 differences 15:25 Gender-related differences 0:25 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats 0:116 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 4 30 theme male 720:723 arg1 rats 736:739 male and female rats 720:739 male and female rats 720:739 In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. 36204299 6 31 from microbes 1024:1031 arg1 rats 1043:1046 female rats 1036:1046 female rats 1036:1046 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 3 32 theme sex 586:588 arg1 effects 575:581 The effects 571:581 The effects of sex on intestinal microbiota after IOP absorption 571:634 The effects of sex on intestinal microbiota after IOP absorption was determined. 36204299 7 33 theme flora 1474:1478 arg1 balance 1448:1454 the balance 1444:1454 the balance of the intestinal flora 1444:1478 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 36204299 5 34 theme same 807:810 arg1 time 812:815 the same time 803:815 the same time 803:815 At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. 36204299 6 35 from genera 1107:1112 arg1 Bacteroidota 1066:1077 Bacteroidota 1066:1077 Bacteroidota from different families and genera 1066:1112 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 7 36 theme SD 1283:1284 arg1 rats 1286:1289 male and female SD rats 1267:1289 male and female SD rats 1267:1289 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 36204299 4 37 theme female 729:734 arg1 rats 736:739 male and female rats 720:739 male and female rats 720:739 In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. 36204299 6 38 theme increasing 1129:1138 arg1 proportion 1140:1149 an increasing proportion 1126:1149 an increasing proportion of Muribaculaceae from different families and genera 1126:1202 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 0 39 from microorganisms 92:105 arg1 differences 15:25 Gender-related differences 0:25 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats 0:116 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 5 40 theme dominant 857:864 arg1 flora 877:881 the dominant intestinal flora 853:881 the dominant intestinal flora of female rats 853:896 At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. 36204299 5 41 theme rats 893:896 arg1 flora 877:881 the dominant intestinal flora 853:881 the dominant intestinal flora of female rats 853:896 At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. 36204299 2 42 theme intestinal 550:559 arg1 immunity 561:568 intestinal immunity 550:568 intestinal immunity 550:568 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 6 43 theme dominant 1004:1011 arg1 Clostridia 955:964 Clostridia 955:964 Clostridia 955:964 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 6 43 theme dominant 1004:1011 arg1 microbes 1024:1031 the dominant intestinal microbes 1000:1031 the dominant intestinal microbes in female rats 1000:1046 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 6 43 theme dominant 1004:1011 arg1 Roseburia 985:993 Roseburia 985:993 Roseburia 985:993 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 6 43 theme dominant 1004:1011 arg1 Lactobacillus 967:979 Lactobacillus 967:979 Lactobacillus 967:979 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 4 44 dep diversity 751:759 arg1 the 747:749 the 747:749 the 747:749 In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. 36204299 5 45 theme IOP 824:826 arg1 intervention 828:839 IOP intervention 824:839 IOP intervention 824:839 At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. 36204299 8 46 theme differences 1541:1551 arg1 effects 1518:1524 the effects 1514:1524 the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases 1514:1622 These results help to understand the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases. 36204299 1 47 theme diseases 223:230 arg1 prevention 209:218 the prevention 205:218 the prevention of diseases 205:230 Natural edible fungal polysaccharides are of research and application value for the prevention of diseases by improving the microenvironment within the intestine. 36204299 0 48 theme obliquus 54:61 arg1 polysaccharide 63:76 Inonotus obliquus polysaccharide 45:76 Inonotus obliquus polysaccharide 45:76 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 8 49 theme sex-related 1529:1539 arg1 differences 1541:1551 sex-related differences 1529:1551 sex-related differences 1529:1551 These results help to understand the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases. 36204299 0 50 theme polysaccharide 63:76 arg1 effects 34:40 the effects 30:40 the effects of Inonotus obliquus polysaccharide on intestinal microorganisms 30:105 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 2 51 theme anti-inflammatory 361:377 arg1 activities 401:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 0 52 theme Inonotus 45:52 arg1 polysaccharide 63:76 Inonotus obliquus polysaccharide 45:76 Inonotus obliquus polysaccharide 45:76 Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model. 36204299 4 53 contain had 671:673 arg1 IOP 667:669 IOP 667:669 IOP 667:669 In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. 36204299 4 53 contain had 671:673 arg2 effects 685:691 different effects 675:691 different effects 675:691 In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. 36204299 3 54 theme intestinal 593:602 arg1 microbiota 604:613 intestinal microbiota 593:613 intestinal microbiota after IOP absorption 593:634 The effects of sex on intestinal microbiota after IOP absorption was determined. 36204299 1 55 theme Natural 125:131 arg1 polysaccharides 147:161 Natural edible fungal polysaccharides 125:161 Natural edible fungal polysaccharides 125:161 Natural edible fungal polysaccharides are of research and application value for the prevention of diseases by improving the microenvironment within the intestine. 36204299 6 56 from genera 1197:1202 arg1 proportion 1140:1149 an increasing proportion 1126:1149 an increasing proportion of Muribaculaceae from different families and genera 1126:1202 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 2 57 contain have 336:339 arg2 activities 401:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 2 57 contain have 336:339 arg1 extracts 327:334 Inonotus obliquus polysaccharide (IOP) extracts 288:334 Inonotus obliquus polysaccharide (IOP) extracts 288:334 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 6 58 contain had 1055:1057 arg1 males 1049:1053 males 1049:1053 males 1049:1053 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 6 58 contain had 1055:1057 arg2 Bacteroidota 1066:1077 Bacteroidota 1066:1077 Bacteroidota from different families and genera 1066:1112 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 4 59 theme opposite 782:789 arg1 changes 791:797 opposite changes 782:797 opposite changes 782:797 In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. 36204299 6 60 from families 1094:1101 arg1 Bacteroidota 1066:1077 Bacteroidota 1066:1077 Bacteroidota from different families and genera 1066:1112 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 1 61 theme edible 133:138 arg1 polysaccharides 147:161 Natural edible fungal polysaccharides 125:161 Natural edible fungal polysaccharides 125:161 Natural edible fungal polysaccharides are of research and application value for the prevention of diseases by improving the microenvironment within the intestine. 36204299 3 62 from effects 575:581 arg1 microbiota 604:613 intestinal microbiota 593:613 intestinal microbiota after IOP absorption 593:634 The effects of sex on intestinal microbiota after IOP absorption was determined. 36204299 5 63 theme female 886:891 arg1 rats 893:896 female rats 886:896 female rats 886:896 At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. 36204299 6 64 theme different 1174:1182 arg1 families 1184:1191 different families 1174:1191 different families 1174:1191 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 1 65 theme fungal 140:145 arg1 polysaccharides 147:161 Natural edible fungal polysaccharides 125:161 Natural edible fungal polysaccharides 125:161 Natural edible fungal polysaccharides are of research and application value for the prevention of diseases by improving the microenvironment within the intestine. 36204299 2 66 theme antioxidant 348:358 arg1 activities 401:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 7 67 theme female 1276:1281 arg1 rats 1286:1289 male and female SD rats 1267:1289 male and female SD rats 1267:1289 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 36204299 3 68 theme IOP 621:623 arg1 absorption 625:634 IOP absorption 621:634 IOP absorption 621:634 The effects of sex on intestinal microbiota after IOP absorption was determined. 36204299 2 69 theme biological 390:399 arg1 activities 401:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 8 70 theme intestinal 1579:1588 arg1 microbiota 1590:1599 the intestinal microbiota 1575:1599 the intestinal microbiota 1575:1599 These results help to understand the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases. 36204299 2 71 theme microbes 496:503 arg1 viability 472:480 the viability 468:480 the viability of intestinal microbes 468:503 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 7 72 theme dominant 1326:1333 arg1 microorganisms 1335:1348 their dominant microorganisms 1320:1348 their dominant microorganisms 1320:1348 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 36204299 6 73 theme Muribaculaceae 1154:1167 arg1 proportion 1140:1149 an increasing proportion 1126:1149 an increasing proportion of Muribaculaceae from different families and genera 1126:1202 In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. 36204299 2 74 theme other 384:388 arg1 activities 401:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 strong antioxidant, anti-inflammatory, and other biological activities 341:410 Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. 36204299 7 75 theme male 1267:1270 arg1 rats 1286:1289 male and female SD rats 1267:1289 male and female SD rats 1267:1289 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 36204299 7 76 theme intestinal 1463:1472 arg1 flora 1474:1478 the intestinal flora 1459:1478 the intestinal flora 1459:1478 IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. 35337819 7 0 theme extracellular 1143:1155 arg1 imbalance 1174:1182 intracellular and extracellular osmotic pressure imbalance 1125:1182 intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant 1125:1272 Moreover, EPS might alleviate intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant. 35337819 8 1 theme High-throughput 1275:1289 arg1 sequencing 1291:1300 High-throughput sequencing 1275:1300 High-throughput sequencing 1275:1300 High-throughput sequencing displayed that nitrifiers (Nitrosomonas, Nitrospira), denitrifiers (Dechloromonas, Hyphomicrobium, Denitromonas, Denitratisoma, Candidatus_Competibacter) and aerobic denitrifiers (Pseudomonas, Thauera) were predominant salt-tolerant bacteria. 35337819 2 2 theme aeration 350:357 arg1 pressure 359:366 aeration pressure 350:366 aeration pressure 350:366 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 0 3 theme Reactor 68:74 arg1 performance 76:86 two-stage MABR system: Reactor performance 45:86 two-stage MABR system: Reactor performance 45:86 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 8 4 theme aerobic 1460:1466 arg1 denitrifiers 1468:1479 aerobic denitrifiers 1460:1479 aerobic denitrifiers (Pseudomonas, Thauera) 1460:1502 High-throughput sequencing displayed that nitrifiers (Nitrosomonas, Nitrospira), denitrifiers (Dechloromonas, Hyphomicrobium, Denitromonas, Denitratisoma, Candidatus_Competibacter) and aerobic denitrifiers (Pseudomonas, Thauera) were predominant salt-tolerant bacteria. 35337819 8 4 theme aerobic 1460:1466 arg1 Thauera 1495:1501 Thauera 1495:1501 Thauera 1495:1501 High-throughput sequencing displayed that nitrifiers (Nitrosomonas, Nitrospira), denitrifiers (Dechloromonas, Hyphomicrobium, Denitromonas, Denitratisoma, Candidatus_Competibacter) and aerobic denitrifiers (Pseudomonas, Thauera) were predominant salt-tolerant bacteria. 35337819 2 5 from effects 326:332 arg1 characteristics 438:452 the treatment efficiency, extracellular polymeric substances (EPS) characteristics 371:452 the treatment efficiency, extracellular polymeric substances (EPS) characteristics 371:452 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 2 5 from effects 326:332 arg1 structure 478:486 microbial community structure 458:486 microbial community structure 458:486 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 6 6 theme environmental 1051:1063 arg1 conditions 1065:1074 environmental conditions 1051:1074 environmental conditions 1051:1074 The results indicated that PN, not PS, response to changes of environmental conditions played a key role. 35337819 1 7 theme steel 247:251 arg1 wastewater 268:277 steel pickling rinse wastewater 247:277 steel pickling rinse wastewater with high salinity and refractory organic 247:319 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 0 8 theme extracellular 89:101 arg1 EPS 125:127 EPS 125:127 EPS 125:127 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 0 8 theme extracellular 89:101 arg1 substances 113:122 extracellular polymeric substances 89:122 extracellular polymeric substances (EPS) 89:128 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 5 9 dep transform 831:839 arg1 infrared 841:848 infrared 841:848 transform infrared spectrum (FTIR) 831:864 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 3 10 theme 4-N 547:549 arg1 efficiencies 522:533 The optimal removal efficiencies 502:533 The optimal removal efficiencies of COD, NH+ 4-N and TN 502:556 The optimal removal efficiencies of COD, NH+ 4-N and TN reached to 62.84%, 99.57% and 51.65%, respectively. 35337819 1 11 theme pickling 253:260 arg1 wastewater 268:277 steel pickling rinse wastewater 247:277 steel pickling rinse wastewater with high salinity and refractory organic 247:319 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 3 12 theme removal 514:520 arg1 efficiencies 522:533 The optimal removal efficiencies 502:533 The optimal removal efficiencies of COD, NH+ 4-N and TN 502:556 The optimal removal efficiencies of COD, NH+ 4-N and TN reached to 62.84%, 99.57% and 51.65%, respectively. 35337819 1 13 theme rinse 262:266 arg1 wastewater 268:277 steel pickling rinse wastewater 247:277 steel pickling rinse wastewater with high salinity and refractory organic 247:319 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 6 14 theme conditions 1065:1074 arg1 changes 1040:1046 changes 1040:1046 changes of environmental conditions 1040:1074 The results indicated that PN, not PS, response to changes of environmental conditions played a key role. 35337819 8 15 dep denitrifiers 1356:1367 arg1 Hyphomicrobium 1385:1398 Hyphomicrobium 1385:1398 Hyphomicrobium 1385:1398 High-throughput sequencing displayed that nitrifiers (Nitrosomonas, Nitrospira), denitrifiers (Dechloromonas, Hyphomicrobium, Denitromonas, Denitratisoma, Candidatus_Competibacter) and aerobic denitrifiers (Pseudomonas, Thauera) were predominant salt-tolerant bacteria. 35337819 8 15 dep denitrifiers 1356:1367 arg1 Candidatus_Competibacter 1430:1453 Candidatus_Competibacter 1430:1453 Candidatus_Competibacter 1430:1453 High-throughput sequencing displayed that nitrifiers (Nitrosomonas, Nitrospira), denitrifiers (Dechloromonas, Hyphomicrobium, Denitromonas, Denitratisoma, Candidatus_Competibacter) and aerobic denitrifiers (Pseudomonas, Thauera) were predominant salt-tolerant bacteria. 35337819 2 16 theme treatment 375:383 arg1 efficiency 385:394 treatment efficiency 375:394 treatment efficiency 375:394 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 2 16 theme treatment 375:383 arg1 substances 421:430 extracellular polymeric substances 397:430 extracellular polymeric substances (EPS) 397:436 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 1 17 theme bench-scale 157:167 arg1 system 219:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 0 18 theme polymeric 103:111 arg1 EPS 125:127 EPS 125:127 EPS 125:127 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 0 18 theme polymeric 103:111 arg1 substances 113:122 extracellular polymeric substances 89:122 extracellular polymeric substances (EPS) 89:128 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 8 19 theme predominant 1509:1519 arg1 bacteria 1535:1542 predominant salt-tolerant bacteria 1509:1542 predominant salt-tolerant bacteria 1509:1542 High-throughput sequencing displayed that nitrifiers (Nitrosomonas, Nitrospira), denitrifiers (Dechloromonas, Hyphomicrobium, Denitromonas, Denitratisoma, Candidatus_Competibacter) and aerobic denitrifiers (Pseudomonas, Thauera) were predominant salt-tolerant bacteria. 35337819 5 20 from content 900:906 arg1 EPS 969:971 EPS 969:971 EPS of the biofilm 969:986 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 3 21 theme NH+ 543:545 arg1 4-N 547:549 NH+ 4-N 543:549 NH+ 4-N 543:549 The optimal removal efficiencies of COD, NH+ 4-N and TN reached to 62.84%, 99.57% and 51.65%, respectively. 35337819 2 22 theme efficiency 385:394 arg1 characteristics 438:452 the treatment efficiency, extracellular polymeric substances (EPS) characteristics 371:452 the treatment efficiency, extracellular polymeric substances (EPS) characteristics 371:452 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 5 23 theme exaction-emission 785:801 arg1 matrix 803:808 three-dimensional exaction-emission matrix 767:808 three-dimensional exaction-emission matrix (3D-EEM) 767:817 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 5 23 theme exaction-emission 785:801 arg1 3D-EEM 811:816 3D-EEM 811:816 3D-EEM 811:816 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 7 24 theme osmotic 1157:1163 arg1 imbalance 1174:1182 intracellular and extracellular osmotic pressure imbalance 1125:1182 intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant 1125:1272 Moreover, EPS might alleviate intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant. 35337819 6 25 dep PN 1016:1017 arg1 PS 1024:1025 PS 1024:1025 PS 1024:1025 The results indicated that PN, not PS, response to changes of environmental conditions played a key role. 35337819 1 26 theme membrane-aerated 179:194 arg1 system 219:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 1 27 with wastewater 268:277 arg1 salinity 289:296 high salinity 284:296 high salinity 284:296 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 1 27 with wastewater 268:277 arg1 organic 313:319 organic 313:319 organic 313:319 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 6 28 theme key 1085:1087 arg1 role 1089:1092 a key role 1083:1092 a key role 1083:1092 The results indicated that PN, not PS, response to changes of environmental conditions played a key role. 35337819 1 29 theme biofilm 196:202 arg1 system 219:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 0 30 theme wastewater 21:30 arg1 treatment 32:40 rinse wastewater treatment 15:40 rinse wastewater treatment 15:40 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 8 31 theme salt-tolerant 1521:1533 arg1 bacteria 1535:1542 predominant salt-tolerant bacteria 1509:1542 predominant salt-tolerant bacteria 1509:1542 High-throughput sequencing displayed that nitrifiers (Nitrosomonas, Nitrospira), denitrifiers (Dechloromonas, Hyphomicrobium, Denitromonas, Denitratisoma, Candidatus_Competibacter) and aerobic denitrifiers (Pseudomonas, Thauera) were predominant salt-tolerant bacteria. 35337819 7 32 with biofilm 1229:1235 arg1 salt-tolerant 1260:1272 prominent salt-tolerant 1250:1272 prominent salt-tolerant 1250:1272 Moreover, EPS might alleviate intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant. 35337819 3 33 theme TN 555:556 arg1 efficiencies 522:533 The optimal removal efficiencies 502:533 The optimal removal efficiencies of COD, NH+ 4-N and TN 502:556 The optimal removal efficiencies of COD, NH+ 4-N and TN reached to 62.84%, 99.57% and 51.65%, respectively. 35337819 1 34 theme reactor 204:210 arg1 system 219:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 0 35 theme rinse 15:19 arg1 treatment 32:40 rinse wastewater treatment 15:40 rinse wastewater treatment 15:40 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 1 36 theme high 284:287 arg1 salinity 289:296 high salinity 284:296 high salinity 284:296 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 4 37 dep salinity 671:678 arg1 % 691:691 % 691:691 % 691:691 Shortcut nitrification was achieved at low aeration, and the salinity less than 4% did not remarkable affect system performance. 35337819 2 38 theme community 468:476 arg1 structure 478:486 microbial community structure 458:486 microbial community structure 458:486 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 5 39 theme Colorimetric 739:750 arg1 determination 752:764 Colorimetric determination 739:764 Colorimetric determination 739:764 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 4 40 theme low 649:651 arg1 aeration 653:660 low aeration 649:660 low aeration 649:660 Shortcut nitrification was achieved at low aeration, and the salinity less than 4% did not remarkable affect system performance. 35337819 2 41 theme polymeric 411:419 arg1 efficiency 385:394 treatment efficiency 375:394 treatment efficiency 375:394 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 2 41 theme polymeric 411:419 arg1 EPS 433:435 EPS 433:435 EPS 433:435 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 2 41 theme polymeric 411:419 arg1 substances 421:430 extracellular polymeric substances 397:430 extracellular polymeric substances (EPS) 397:436 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 1 42 theme MABR 213:216 arg1 system 219:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 7 43 theme prominent 1250:1258 arg1 salt-tolerant 1260:1272 prominent salt-tolerant 1250:1272 prominent salt-tolerant 1250:1272 Moreover, EPS might alleviate intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant. 35337819 7 44 from biofilm 1229:1235 arg1 MABR 1240:1243 MABR 1240:1243 MABR 1240:1243 Moreover, EPS might alleviate intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant. 35337819 2 45 theme extracellular 397:409 arg1 efficiency 385:394 treatment efficiency 375:394 treatment efficiency 375:394 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 2 45 theme extracellular 397:409 arg1 EPS 433:435 EPS 433:435 EPS 433:435 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 2 45 theme extracellular 397:409 arg1 substances 421:430 extracellular polymeric substances 397:430 extracellular polymeric substances (EPS) 397:436 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 0 46 theme MABR 55:58 arg1 performance 76:86 two-stage MABR system: Reactor performance 45:86 two-stage MABR system: Reactor performance 45:86 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 7 47 theme intracellular 1125:1137 arg1 imbalance 1174:1182 intracellular and extracellular osmotic pressure imbalance 1125:1182 intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant 1125:1272 Moreover, EPS might alleviate intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant. 35337819 5 48 theme three-dimensional 767:783 arg1 matrix 803:808 three-dimensional exaction-emission matrix 767:808 three-dimensional exaction-emission matrix (3D-EEM) 767:817 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 5 48 theme three-dimensional 767:783 arg1 3D-EEM 811:816 3D-EEM 811:816 3D-EEM 811:816 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 2 49 theme salinity 337:344 arg1 effects 326:332 The effects 322:332 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure 322:486 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 0 50 theme two-stage 45:53 arg1 performance 76:86 two-stage MABR system: Reactor performance 45:86 two-stage MABR system: Reactor performance 45:86 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 0 51 theme microbial 134:142 arg1 community 144:152 microbial community 134:152 microbial community 134:152 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 2 52 theme microbial 458:466 arg1 structure 478:486 microbial community structure 458:486 microbial community structure 458:486 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 5 53 theme biofilm 980:986 arg1 EPS 969:971 EPS 969:971 EPS of the biofilm 969:986 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 3 54 theme optimal 506:512 arg1 efficiencies 522:533 The optimal removal efficiencies 502:533 The optimal removal efficiencies of COD, NH+ 4-N and TN 502:556 The optimal removal efficiencies of COD, NH+ 4-N and TN reached to 62.84%, 99.57% and 51.65%, respectively. 35337819 5 55 dep Fourier 823:829 arg1 transform 831:839 transform 831:839 transform infrared spectrum (FTIR) 831:864 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 5 56 theme proteins 927:934 arg1 composition 912:922 composition 912:922 composition 912:922 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 5 56 theme proteins 927:934 arg1 content 900:906 content 900:906 content 900:906 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 5 57 theme polysaccharides 945:959 arg1 composition 912:922 composition 912:922 composition 912:922 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 5 57 theme polysaccharides 945:959 arg1 content 900:906 content 900:906 content 900:906 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 5 58 dep content 900:906 arg1 the 896:898 the 896:898 the 896:898 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 4 59 theme system 719:724 arg1 performance 726:736 system performance 719:736 system performance 719:736 Shortcut nitrification was achieved at low aeration, and the salinity less than 4% did not remarkable affect system performance. 35337819 3 60 theme COD 538:540 arg1 efficiencies 522:533 The optimal removal efficiencies 502:533 The optimal removal efficiencies of COD, NH+ 4-N and TN 502:556 The optimal removal efficiencies of COD, NH+ 4-N and TN reached to 62.84%, 99.57% and 51.65%, respectively. 35337819 5 61 from composition 912:922 arg1 EPS 969:971 EPS 969:971 EPS of the biofilm 969:986 Colorimetric determination, three-dimensional exaction-emission matrix (3D-EEM) and Fourier transform infrared spectrum (FTIR) were employed to characterize the content and composition of proteins (PN) and polysaccharides (PS) in EPS of the biofilm. 35337819 7 62 theme pressure 1165:1172 arg1 imbalance 1174:1182 intracellular and extracellular osmotic pressure imbalance 1125:1182 intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant 1125:1272 Moreover, EPS might alleviate intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant. 35337819 4 63 theme Shortcut 610:617 arg1 nitrification 619:631 Shortcut nitrification 610:631 Shortcut nitrification 610:631 Shortcut nitrification was achieved at low aeration, and the salinity less than 4% did not remarkable affect system performance. 35337819 7 64 theme high 1195:1198 arg1 salinity 1200:1207 high salinity 1195:1207 high salinity 1195:1207 Moreover, EPS might alleviate intracellular and extracellular osmotic pressure imbalance induced by high salinity, which imparted the biofilm in MABR with prominent salt-tolerant. 35337819 1 65 theme two-stage 169:177 arg1 system 219:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system 155:224 A bench-scale two-stage membrane-aerated biofilm reactor (MABR) system was applied to treat steel pickling rinse wastewater with high salinity and refractory organic. 35337819 0 66 theme system 60:65 arg1 performance 76:86 two-stage MABR system: Reactor performance 45:86 two-stage MABR system: Reactor performance 45:86 Steel pickling rinse wastewater treatment by two-stage MABR system: Reactor performance, extracellular polymeric substances (EPS) and microbial community. 35337819 4 67 dep % 691:691 arg1 4 690:690 4 690:690 4 690:690 Shortcut nitrification was achieved at low aeration, and the salinity less than 4% did not remarkable affect system performance. 35337819 2 68 theme pressure 359:366 arg1 effects 326:332 The effects 322:332 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure 322:486 The effects of salinity and aeration pressure on the treatment efficiency, extracellular polymeric substances (EPS) characteristics and microbial community structure were studied. 35337819 8 69 dep Nitrosomonas 1329:1340 arg1 Nitrospira 1343:1352 Nitrospira 1343:1352 Nitrospira 1343:1352 High-throughput sequencing displayed that nitrifiers (Nitrosomonas, Nitrospira), denitrifiers (Dechloromonas, Hyphomicrobium, Denitromonas, Denitratisoma, Candidatus_Competibacter) and aerobic denitrifiers (Pseudomonas, Thauera) were predominant salt-tolerant bacteria. 37202179 1 0 theme cell-cell 156:164 arg1 recognition 166:176 cell-cell recognition 156:176 cell-cell recognition 156:176 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 4 1 theme endo-acting 535:545 arg1 mannosidase 547:557 the only endo-acting mannosidase 526:557 the only endo-acting mannosidase found in this organelle 526:581 It is unique as the only endo-acting mannosidase found in this organelle. 37202179 6 2 theme major 822:826 arg1 clades 839:844 all major eukaryotic clades 818:844 all major eukaryotic clades 818:844 In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. 37202179 9 3 theme duplications 1226:1237 arg1 round 1191:1195 the second round 1180:1195 the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, 1180:1279 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 2 4 from enzymes 337:343 arg1 process 290:296 a conserved process 278:296 a conserved process in which mannosidases are key trimming enzymes 278:343 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 2 4 from enzymes 337:343 arg1 glycosylation 261:273 N-linked glycosylation 252:273 N-linked glycosylation 252:273 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 3 5 theme glycoprotein 365:376 arg1 them 353:356 them 353:356 them 353:356 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 3 5 theme glycoprotein 365:376 arg1 One 346:348 One 346:348 One 346:348 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 3 5 theme glycoprotein 365:376 arg1 endo-α-1,2-mannosidase 378:399 the glycoprotein endo-α-1,2-mannosidase 361:399 the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi 361:507 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 8 6 theme canonical 1035:1043 arg1 enzyme 1052:1057 the canonical animal enzyme 1031:1057 the canonical animal enzyme 1031:1057 The protein motif changes in context of the canonical animal enzyme were tracked. 37202179 11 7 from eukaryotes 1503:1512 arg1 general 1517:1523 general 1517:1523 general 1517:1523 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 9 8 theme canonical 1109:1117 arg1 MANEA 1153:1157 MANEA 1153:1157 MANEA 1153:1157 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 9 8 theme canonical 1109:1117 arg1 genes 1146:1150 the two canonical vertebrate endomannosidase genes 1101:1150 the two canonical vertebrate endomannosidase genes 1101:1150 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 9 8 theme canonical 1109:1117 arg1 MANEAL 1163:1168 MANEAL 1163:1168 MANEAL 1163:1168 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 5 9 theme evolutionary 633:644 arg1 history 646:652 evolutionary history 633:652 evolutionary history 633:652 Relatively little is known about its origins and evolutionary history; so far it was reported to occur only in vertebrates. 37202179 8 10 theme enzyme 1052:1057 arg1 context 1020:1026 context 1020:1026 context of the canonical animal enzyme 1020:1057 The protein motif changes in context of the canonical animal enzyme were tracked. 37202179 1 11 theme many 86:89 arg1 adhesion 143:150 cell adhesion 138:150 cell adhesion 138:150 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 1 11 theme many 86:89 arg1 folding 129:135 protein folding 121:135 protein folding 121:135 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 1 11 theme many 86:89 arg1 processes 102:110 many biological processes 86:110 many biological processes 86:110 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 1 11 theme many 86:89 arg1 recognition 166:176 cell-cell recognition 156:176 cell-cell recognition 156:176 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 11 12 theme core 1436:1439 arg1 pathways 1455:1462 core glycosylation pathways 1436:1462 core glycosylation pathways 1436:1462 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 11 13 theme better 1395:1400 arg1 understanding 1402:1414 A better understanding 1393:1414 A better understanding of the evolution of core glycosylation pathways 1393:1462 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 11 13 theme better 1395:1400 arg1 pivotal 1467:1473 pivotal 1467:1473 pivotal 1467:1473 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 8 14 theme animal 1045:1050 arg1 enzyme 1052:1057 the canonical animal enzyme 1031:1057 the canonical animal enzyme 1031:1057 The protein motif changes in context of the canonical animal enzyme were tracked. 37202179 6 15 theme enzyme 800:805 arg1 history 784:790 the evolutionary history 767:790 the evolutionary history of this enzyme 767:805 In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. 37202179 1 16 theme biological 91:100 arg1 adhesion 143:150 cell adhesion 138:150 cell adhesion 138:150 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 1 16 theme biological 91:100 arg1 folding 129:135 protein folding 121:135 protein folding 121:135 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 1 16 theme biological 91:100 arg1 processes 102:110 many biological processes 86:110 many biological processes 86:110 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 1 16 theme biological 91:100 arg1 recognition 166:176 cell-cell recognition 156:176 cell-cell recognition 156:176 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 1 17 theme deep 179:182 arg1 evolution 184:192 deep evolution 179:192 deep evolution of glycosylation machinery 179:219 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 9 18 theme vertebrate 1252:1261 arg1 CMANEAL 1272:1278 CMANEAL 1272:1278 CMANEAL 1272:1278 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 9 18 theme vertebrate 1252:1261 arg1 paralog 1263:1269 one more vertebrate paralog 1243:1269 one more vertebrate paralog 1243:1269 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 8 19 theme protein 995:1001 arg1 changes 1009:1015 The protein motif changes 991:1015 The protein motif changes in context of the canonical animal enzyme 991:1057 The protein motif changes in context of the canonical animal enzyme were tracked. 37202179 11 20 theme evolution 1423:1431 arg1 understanding 1402:1414 A better understanding 1393:1414 A better understanding of the evolution of core glycosylation pathways 1393:1462 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 11 20 theme evolution 1423:1431 arg1 pivotal 1467:1473 pivotal 1467:1473 pivotal 1467:1473 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 3 21 theme moieties 455:462 arg1 trimming 435:442 the initial trimming 423:442 the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi 423:507 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 12 22 theme evolution 1613:1621 arg1 analysis 1581:1588 This systematic analysis 1565:1588 This systematic analysis of the endomannosidase evolution 1565:1621 This systematic analysis of the endomannosidase evolution is one step towards this goal. 37202179 3 23 link N-linked 472:479 arg1 glycan 481:486 an N-linked glycan 469:486 an N-linked glycan inside the cis-Golgi 469:507 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 2 24 theme trimming 328:335 arg1 mannosidases 307:318 mannosidases 307:318 mannosidases 307:318 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 2 24 theme trimming 328:335 arg1 enzymes 337:343 key trimming enzymes 324:343 key trimming enzymes 324:343 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 12 25 theme endomannosidase 1597:1611 arg1 evolution 1613:1621 the endomannosidase evolution 1593:1621 the endomannosidase evolution 1593:1621 This systematic analysis of the endomannosidase evolution is one step towards this goal. 37202179 11 26 from biology 1492:1498 arg1 particular 1553:1562 particular 1553:1562 particular 1553:1562 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 11 26 from biology 1492:1498 arg1 general 1517:1523 general 1517:1523 general 1517:1523 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 2 27 theme key 324:326 arg1 mannosidases 307:318 mannosidases 307:318 mannosidases 307:318 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 2 27 theme key 324:326 arg1 enzymes 337:343 key trimming enzymes 324:343 key trimming enzymes 324:343 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 11 28 theme Golgi 1534:1538 arg1 apparatus 1540:1548 the Golgi apparatus 1530:1548 the Golgi apparatus in particular 1530:1562 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 1 29 theme glycosylation 197:209 arg1 machinery 211:219 glycosylation machinery 197:219 glycosylation machinery 197:219 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 0 30 theme phylogenetic 14:25 arg1 distribution 27:38 phylogenetic distribution 14:38 phylogenetic distribution 14:38 Evolution and phylogenetic distribution of endo-α-mannosidase. 37202179 3 31 gly glycoprotein 365:376 arg1 glycoprotein 365:376 the glycoprotein endo-α-1,2-mannosidase 361:399 the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi 361:507 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 6 32 theme animals 875:881 arg1 representation 857:870 a wide representation 850:870 a wide representation of animals 850:881 In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. 37202179 6 32 theme animals 875:881 arg1 clades 839:844 all major eukaryotic clades 818:844 all major eukaryotic clades 818:844 In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. 37202179 11 33 from apparatus 1540:1548 arg1 particular 1553:1562 particular 1553:1562 particular 1553:1562 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 11 33 from apparatus 1540:1548 arg1 general 1517:1523 general 1517:1523 general 1517:1523 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 11 34 theme glycosylation 1441:1453 arg1 pathways 1455:1462 core glycosylation pathways 1436:1462 core glycosylation pathways 1436:1462 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 1 35 theme machinery 211:219 arg1 evolution 184:192 deep evolution 179:192 deep evolution of glycosylation machinery 179:219 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 0 36 theme endo-α-mannosidase 43:60 arg1 Evolution 0:8 Evolution 0:8 Evolution 0:8 Evolution and phylogenetic distribution of endo-α-mannosidase. 37202179 0 36 theme endo-α-mannosidase 43:60 arg1 distribution 27:38 phylogenetic distribution 14:38 phylogenetic distribution 14:38 Evolution and phylogenetic distribution of endo-α-mannosidase. 37202179 9 37 theme vertebrate 1208:1217 arg1 duplications 1226:1237 the two vertebrate genome duplications 1200:1237 the two vertebrate genome duplications 1200:1237 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 2 38 theme N-linked 252:259 arg1 process 290:296 a conserved process 278:296 a conserved process in which mannosidases are key trimming enzymes 278:343 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 2 38 theme N-linked 252:259 arg1 glycosylation 261:273 N-linked glycosylation 252:273 N-linked glycosylation 252:273 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 11 39 theme pathways 1455:1462 arg1 evolution 1423:1431 the evolution 1419:1431 the evolution of core glycosylation pathways 1419:1462 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 3 40 theme mannose 447:453 arg1 moieties 455:462 mannose moieties 447:462 mannose moieties 447:462 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 7 41 theme other 973:977 arg1 eukaryotes 979:988 other eukaryotes 973:988 other eukaryotes 973:988 The endomannosidase was found to be more widely distributed in animals and other eukaryotes. 37202179 9 42 theme genome 1219:1224 arg1 duplications 1226:1237 the two vertebrate genome duplications 1200:1237 the two vertebrate genome duplications 1200:1237 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 3 43 from glycan 481:486 arg1 trimming 435:442 the initial trimming 423:442 the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi 423:507 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 11 44 from general 1517:1523 arg1 biology 1492:1498 biology 1492:1498 biology of eukaryotes in general 1492:1523 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 11 44 from general 1517:1523 arg1 apparatus 1540:1548 the Golgi apparatus 1530:1548 the Golgi apparatus in particular 1530:1562 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 3 45 theme initial 427:433 arg1 trimming 435:442 the initial trimming 423:442 the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi 423:507 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 12 46 theme systematic 1570:1579 arg1 analysis 1581:1588 This systematic analysis 1565:1588 This systematic analysis of the endomannosidase evolution 1565:1621 This systematic analysis of the endomannosidase evolution is one step towards this goal. 37202179 6 47 theme wide 852:855 arg1 representation 857:870 a wide representation 850:870 a wide representation of animals 850:881 In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. 37202179 9 48 theme vertebrate 1119:1128 arg1 MANEA 1153:1157 MANEA 1153:1157 MANEA 1153:1157 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 9 48 theme vertebrate 1119:1128 arg1 genes 1146:1150 the two canonical vertebrate endomannosidase genes 1101:1150 the two canonical vertebrate endomannosidase genes 1101:1150 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 9 48 theme vertebrate 1119:1128 arg1 MANEAL 1163:1168 MANEAL 1163:1168 MANEAL 1163:1168 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 1 49 theme protein 121:127 arg1 folding 129:135 protein folding 121:135 protein folding 121:135 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 11 50 theme eukaryotes 1503:1512 arg1 biology 1492:1498 biology 1492:1498 biology of eukaryotes in general 1492:1523 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 11 50 theme eukaryotes 1503:1512 arg1 apparatus 1540:1548 the Golgi apparatus 1530:1548 the Golgi apparatus in particular 1530:1562 A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. 37202179 9 51 theme endomannosidase 1130:1144 arg1 MANEA 1153:1157 MANEA 1153:1157 MANEA 1153:1157 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 9 51 theme endomannosidase 1130:1144 arg1 genes 1146:1150 the two canonical vertebrate endomannosidase genes 1101:1150 the two canonical vertebrate endomannosidase genes 1101:1150 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 9 51 theme endomannosidase 1130:1144 arg1 MANEAL 1163:1168 MANEAL 1163:1168 MANEAL 1163:1168 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 8 52 theme motif 1003:1007 arg1 changes 1009:1015 The protein motif changes 991:1015 The protein motif changes in context of the canonical animal enzyme 991:1057 The protein motif changes in context of the canonical animal enzyme were tracked. 37202179 2 53 theme conserved 280:288 arg1 process 290:296 a conserved process 278:296 a conserved process in which mannosidases are key trimming enzymes 278:343 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 2 53 theme conserved 280:288 arg1 glycosylation 261:273 N-linked glycosylation 252:273 N-linked glycosylation 252:273 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 9 54 theme second 1184:1189 arg1 round 1191:1195 the second round 1180:1195 the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, 1180:1279 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 4 55 located found 559:563 arg2 mannosidase 547:557 the only endo-acting mannosidase 526:557 the only endo-acting mannosidase found in this organelle 526:581 It is unique as the only endo-acting mannosidase found in this organelle. 37202179 4 55 located found 559:563 arg1 organelle 573:581 this organelle 568:581 this organelle 568:581 It is unique as the only endo-acting mannosidase found in this organelle. 37202179 1 56 theme understudied 232:243 arg1 topic 245:249 an understudied topic 229:249 an understudied topic 229:249 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 6 57 theme evolutionary 771:782 arg1 history 784:790 the evolutionary history 767:790 the evolutionary history of this enzyme 767:805 In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. 37202179 10 58 theme complex 1354:1360 arg1 multicellularity 1362:1377 complex multicellularity 1354:1377 complex multicellularity 1354:1377 Finally, a framework where N-glycosylation co-evolved with complex multicellularity is described. 37202179 1 59 theme cell 138:141 arg1 adhesion 143:150 cell adhesion 138:150 cell adhesion 138:150 While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. 37202179 6 60 dep survey 749:754 arg1 unravel 759:765 unravel 759:765 to unravel the evolutionary history of this enzyme 756:805 In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. 37202179 6 61 theme eukaryotic 828:837 arg1 clades 839:844 all major eukaryotic clades 818:844 all major eukaryotic clades 818:844 In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. 37202179 6 62 theme bioinformatic 735:747 arg1 survey 749:754 a taxon-rich bioinformatic survey 722:754 a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme 722:805 In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. 37202179 3 63 theme N-linked 472:479 arg1 glycan 481:486 an N-linked glycan 469:486 an N-linked glycan inside the cis-Golgi 469:507 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 2 64 link N-linked 252:259 arg1 process 290:296 a conserved process 278:296 a conserved process in which mannosidases are key trimming enzymes 278:343 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 2 64 link N-linked 252:259 arg1 glycosylation 261:273 N-linked glycosylation 252:273 N-linked glycosylation 252:273 N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. 37202179 3 65 theme them 353:356 arg1 them 353:356 them 353:356 them 353:356 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 3 65 theme them 353:356 arg1 One 346:348 One 346:348 One 346:348 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 3 65 theme them 353:356 arg1 endo-α-1,2-mannosidase 378:399 the glycoprotein endo-α-1,2-mannosidase 361:399 the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi 361:507 One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. 37202179 9 66 theme paralog 1263:1269 arg1 round 1191:1195 the second round 1180:1195 the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, 1180:1279 Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. 37202179 6 67 theme taxon-rich 724:733 arg1 survey 749:754 a taxon-rich bioinformatic survey 722:754 a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme 722:805 In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. 37202179 8 68 from changes 1009:1015 arg1 context 1020:1026 context 1020:1026 context of the canonical animal enzyme 1020:1057 The protein motif changes in context of the canonical animal enzyme were tracked. 35832079 8 0 theme cancerous 1204:1212 arg1 regions 1248:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. 35832079 11 1 theme analyzed 1538:1545 arg1 cancers 1547:1553 the analyzed cancers 1534:1553 the analyzed cancers 1534:1553 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 8 2 theme stromal 1215:1221 arg1 regions 1248:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. 35832079 6 3 theme sites 941:945 arg1 tissues 895:901 formalin fixed paraffin embedded tissues 862:901 formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites 862:945 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 6 4 theme laser 829:833 arg1 microdissection 843:857 laser capture microdissection 829:857 laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites 829:945 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 8 5 theme normal 1227:1232 arg1 regions 1248:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. 35832079 5 6 link O-linked 740:747 arg1 glycans 749:755 the colorectal cancer (CRC)-associated O-linked glycans 701:755 the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts 701:795 Methods: A workflow was established to decode the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts. 35832079 8 7 theme mucosal 1240:1246 arg1 regions 1248:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. 35832079 6 8 theme primary 911:917 arg1 tumors 919:924 primary tumors 911:924 primary tumors 911:924 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 9 9 theme O-linked 1266:1273 arg1 glycans 1275:1281 Over 100 O-linked glycans 1257:1281 Over 100 O-linked glycans 1257:1281 Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. 35832079 6 10 theme same 994:997 arg1 patients 999:1006 the same patients 990:1006 the same patients 990:1006 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 12 11 theme sialylation 1734:1744 arg1 antigens 1772:1779 α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens 1722:1779 α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens 1722:1779 In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. 35832079 7 12 theme negative 1125:1132 arg1 mode 1138:1141 negative ion mode 1125:1141 negative ion mode 1125:1141 The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. 35832079 6 13 theme colon 972:976 arg1 mucosa 978:983 healthy colon mucosa 964:983 healthy colon mucosa from the same patients 964:1006 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 7 14 theme chromatography-tandem 1082:1102 arg1 spectrometry 1109:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry 1049:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode 1049:1141 The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. 35832079 0 15 from epithelium 92:101 arg1 cancer 66:71 colorectal cancer 55:71 colorectal cancer from healthy colon epithelium 55:101 Specific (sialyl-)Lewis core 2 O-glycans differentiate colorectal cancer from healthy colon epithelium. 35832079 11 16 theme cancers 1547:1553 arg1 cancers 1583:1589 the investigated cancers 1566:1589 the investigated cancers 1566:1589 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 11 16 theme cancers 1547:1553 arg1 cancers 1547:1553 the analyzed cancers 1534:1553 the analyzed cancers 1534:1553 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 11 16 theme cancers 1547:1553 arg1 % 1561:1561 94% 1559:1561 94% of the investigated cancers 1559:1589 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 11 16 theme cancers 1547:1553 arg1 % 1529:1529 72% 1527:1529 72% of the analyzed cancers 1527:1553 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 7 17 theme carbon 1068:1073 arg1 spectrometry 1109:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry 1049:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode 1049:1141 The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. 35832079 1 18 located present 184:190 arg1 cells 206:210 neoplastic cells 195:210 neoplastic cells 195:210 Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. 35832079 1 18 located present 184:190 arg2 carbohydrates 144:156 carbohydrates 144:156 carbohydrates 144:156 Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. 35832079 1 18 located present 184:190 arg2 some 159:162 some 159:162 some 159:162 Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. 35832079 2 19 theme tumor-associated 227:242 arg1 TACAs 267:271 TACAs 267:271 TACAs 267:271 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 2 19 theme tumor-associated 227:242 arg1 antigens 257:264 The so-called tumor-associated carbohydrate antigens 213:264 The so-called tumor-associated carbohydrate antigens (TACAs) 213:272 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 2 19 theme tumor-associated 227:242 arg1 targets 315:321 promising targets 305:321 promising targets for immunotherapy 305:339 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 7 20 theme released 1013:1020 arg1 O-glycans 1022:1030 The released O-glycans 1009:1030 The released O-glycans 1009:1030 The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. 35832079 9 21 theme normal 1334:1339 arg1 mucosa 1341:1346 normal mucosa 1334:1346 normal mucosa 1334:1346 Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. 35832079 1 22 theme dense 129:133 arg1 layer 135:139 a dense layer 127:139 a dense layer of carbohydrates, some of which are solely present on neoplastic cells 127:210 Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. 35832079 4 23 theme tissue 568:573 arg1 heterogeneity 575:587 tumor tissue heterogeneity 562:587 tumor tissue heterogeneity 562:587 However, due to tumor tissue heterogeneity and technological limitations, TACAs are insufficiently explored. 35832079 5 24 theme colorectal 705:714 arg1 CRC 724:726 CRC 724:726 CRC 724:726 Methods: A workflow was established to decode the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts. 35832079 5 24 theme colorectal 705:714 arg1 cancer 716:721 colorectal cancer 705:721 colorectal cancer (CRC) 705:727 Methods: A workflow was established to decode the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts. 35832079 13 25 theme specific 1844:1851 arg1 TACAs 1853:1857 highly specific TACAs 1837:1857 highly specific TACAs 1837:1857 Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. 35832079 13 26 theme healthy 1924:1930 arg1 mucosa 1938:1943 healthy colon mucosa 1924:1943 healthy colon mucosa 1924:1943 Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. 35832079 0 27 theme healthy 78:84 arg1 epithelium 92:101 healthy colon epithelium 78:101 healthy colon epithelium 78:101 Specific (sialyl-)Lewis core 2 O-glycans differentiate colorectal cancer from healthy colon epithelium. 35832079 14 28 theme new 1972:1974 arg1 TACAs 1952:1956 These TACAs 1946:1956 These TACAs 1946:1956 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 14 28 theme new 1972:1974 arg1 targets 1976:1982 promising new targets 1962:1982 promising new targets for development of innovative cancer immune target therapies 1962:2043 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 14 29 theme immune 2021:2026 arg1 therapies 2035:2043 innovative cancer immune target therapies 2003:2043 innovative cancer immune target therapies 2003:2043 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 13 30 theme novel 1822:1826 arg1 panel 1828:1832 a novel panel 1820:1832 a novel panel 1820:1832 Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. 35832079 13 31 attach present 1812:1818 arg1 study 1802:1806 this study 1797:1806 this study 1797:1806 Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. 35832079 13 31 attach present 1812:1818 arg2 we 1809:1810 we 1809:1810 we 1809:1810 Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. 35832079 12 32 theme normal 1651:1656 arg1 mucosa 1664:1669 normal colon mucosa 1651:1669 normal colon mucosa 1651:1669 In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. 35832079 4 33 theme tumor 562:566 arg1 heterogeneity 575:587 tumor tissue heterogeneity 562:587 tumor tissue heterogeneity 562:587 However, due to tumor tissue heterogeneity and technological limitations, TACAs are insufficiently explored. 35832079 0 34 theme Specific 0:7 arg1 O-glycans 31:39 Specific (sialyl-)Lewis core 2 O-glycans 0:39 Specific (sialyl-)Lewis core 2 O-glycans 0:39 Specific (sialyl-)Lewis core 2 O-glycans differentiate colorectal cancer from healthy colon epithelium. 35832079 14 35 theme therapies 2035:2043 arg1 development 1988:1998 development 1988:1998 development of innovative cancer immune target therapies 1988:2043 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 6 36 dep fixed 871:875 arg1 embedded 886:893 embedded 886:893 embedded 886:893 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 6 37 from patients 999:1006 arg1 mucosa 978:983 healthy colon mucosa 964:983 healthy colon mucosa from the same patients 964:1006 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 0 38 theme Lewis 18:22 arg1 O-glycans 31:39 Specific (sialyl-)Lewis core 2 O-glycans 0:39 Specific (sialyl-)Lewis core 2 O-glycans 0:39 Specific (sialyl-)Lewis core 2 O-glycans differentiate colorectal cancer from healthy colon epithelium. 35832079 6 39 theme tissues 895:901 arg1 microdissection 843:857 laser capture microdissection 829:857 laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites 829:945 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 3 40 theme surrounding 387:397 arg1 tissues 413:419 the surrounding non-cancerous tissues 383:419 the surrounding non-cancerous tissues 383:419 These carbohydrates differ from those of the surrounding non-cancerous tissues and contribute to the malignant phenotype of the cancer cells by promoting proliferation, metastasis, and immunosuppression. 35832079 14 41 theme innovative 2003:2012 arg1 therapies 2035:2043 innovative cancer immune target therapies 2003:2043 innovative cancer immune target therapies 2003:2043 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 9 42 located detected 1288:1295 arg2 glycans 1275:1281 Over 100 O-linked glycans 1257:1281 Over 100 O-linked glycans 1257:1281 Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. 35832079 9 42 located detected 1288:1295 arg1 regions 1310:1316 cancerous regions 1300:1316 cancerous regions with absence in normal mucosa 1300:1346 Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. 35832079 11 43 theme investigated 1570:1581 arg1 cancers 1583:1589 the investigated cancers 1566:1589 the investigated cancers 1566:1589 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 3 44 theme cells 477:481 arg1 phenotype 453:461 the malignant phenotype 439:461 the malignant phenotype of the cancer cells 439:481 These carbohydrates differ from those of the surrounding non-cancerous tissues and contribute to the malignant phenotype of the cancer cells by promoting proliferation, metastasis, and immunosuppression. 35832079 8 45 theme O-glycosylation 1165:1179 arg1 features 1181:1188 Distinctive O-glycosylation features 1153:1188 Distinctive O-glycosylation features 1153:1188 Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. 35832079 12 46 theme Sda 1768:1770 arg1 antigens 1772:1779 α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens 1722:1779 α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens 1722:1779 In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. 35832079 0 47 dep Specific 0:7 arg1 sialyl- 10:16 sialyl- 10:16 sialyl- 10:16 Specific (sialyl-)Lewis core 2 O-glycans differentiate colorectal cancer from healthy colon epithelium. 35832079 12 48 theme sulfo- 1748:1753 arg1 LewisX/A 1755:1762 (sulfo-)LewisX/A 1747:1762 (sulfo-)LewisX/A 1747:1762 In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. 35832079 7 49 from spectrometry 1109:1120 arg1 mode 1138:1141 negative ion mode 1125:1141 negative ion mode 1125:1141 The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. 35832079 6 50 theme capture 835:841 arg1 microdissection 843:857 laser capture microdissection 829:857 laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites 829:945 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 10 51 contain carrying 1438:1445 arg2 antigen 1478:1484 the terminal (sialyl-)LewisX/A antigen 1447:1484 the terminal (sialyl-)LewisX/A antigen 1447:1484 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 10 51 contain carrying 1438:1445 arg1 cancers 1429:1435 the cancers 1425:1435 the cancers 1425:1435 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 6 52 theme metastatic 930:939 arg1 sites 941:945 metastatic sites 930:945 metastatic sites 930:945 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 12 53 theme LewisX/A 1755:1762 arg1 antigens 1772:1779 α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens 1722:1779 α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens 1722:1779 In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. 35832079 4 54 theme technological 593:605 arg1 limitations 607:617 technological limitations 593:617 technological limitations 593:617 However, due to tumor tissue heterogeneity and technological limitations, TACAs are insufficiently explored. 35832079 13 55 theme colon 1932:1936 arg1 mucosa 1938:1943 healthy colon mucosa 1924:1943 healthy colon mucosa 1924:1943 Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. 35832079 1 56 theme carbohydrates 144:156 arg1 layer 135:139 a dense layer 127:139 a dense layer of carbohydrates, some of which are solely present on neoplastic cells 127:210 Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. 35832079 6 57 theme tumors 919:924 arg1 tissues 895:901 formalin fixed paraffin embedded tissues 862:901 formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites 862:945 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 12 58 theme α2-6-linked 1722:1732 arg1 antigens 1772:1779 α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens 1722:1779 α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens 1722:1779 In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. 35832079 7 59 theme ion 1134:1136 arg1 mode 1138:1141 negative ion mode 1125:1141 negative ion mode 1125:1141 The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. 35832079 13 60 theme glycomic 1890:1897 arg1 profiles 1899:1906 the glycomic profiles 1886:1906 the glycomic profiles between CRC and healthy colon mucosa 1886:1943 Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. 35832079 8 61 theme colon 1234:1238 arg1 regions 1248:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. 35832079 14 62 theme targeted 2076:2083 arg1 treatment 2085:2093 the targeted treatment 2072:2093 the targeted treatment of CRC 2072:2100 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 10 63 theme cancers 1429:1435 arg1 % 1420:1420 more than 33% 1408:1420 more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen 1408:1484 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 10 63 theme cancers 1429:1435 arg1 cancers 1429:1435 the cancers 1425:1435 the cancers 1425:1435 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 7 64 theme mass 1104:1107 arg1 spectrometry 1109:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry 1049:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode 1049:1141 The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. 35832079 14 65 theme CRC 2098:2100 arg1 treatment 2085:2093 the targeted treatment 2072:2093 the targeted treatment of CRC 2072:2100 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 5 66 theme -associated 728:738 arg1 glycans 749:755 the colorectal cancer (CRC)-associated O-linked glycans 701:755 the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts 701:795 Methods: A workflow was established to decode the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts. 35832079 7 67 theme liquid 1075:1080 arg1 spectrometry 1109:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry 1049:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode 1049:1141 The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. 35832079 9 68 theme cancerous 1300:1308 arg1 regions 1310:1316 cancerous regions 1300:1316 cancerous regions with absence in normal mucosa 1300:1346 Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. 35832079 7 69 theme porous 1049:1054 arg1 spectrometry 1109:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry 1049:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode 1049:1141 The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. 35832079 6 70 theme healthy 964:970 arg1 mucosa 978:983 healthy colon mucosa 964:983 healthy colon mucosa from the same patients 964:1006 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 7 71 theme graphitized 1056:1066 arg1 spectrometry 1109:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry 1049:1120 porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode 1049:1141 The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. 35832079 5 72 from extracts 788:795 arg1 glycans 749:755 the colorectal cancer (CRC)-associated O-linked glycans 701:755 the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts 701:795 Methods: A workflow was established to decode the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts. 35832079 2 73 theme carbohydrate 244:255 arg1 TACAs 267:271 TACAs 267:271 TACAs 267:271 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 2 73 theme carbohydrate 244:255 arg1 antigens 257:264 The so-called tumor-associated carbohydrate antigens 213:264 The so-called tumor-associated carbohydrate antigens (TACAs) 213:272 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 2 73 theme carbohydrate 244:255 arg1 targets 315:321 promising targets 305:321 promising targets for immunotherapy 305:339 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 12 74 theme core 1695:1698 arg1 O-glycans 1702:1710 core 3 O-glycans 1695:1710 core 3 O-glycans 1695:1710 In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. 35832079 0 75 theme colorectal 55:64 arg1 cancer 66:71 colorectal cancer 55:71 colorectal cancer from healthy colon epithelium 55:101 Specific (sialyl-)Lewis core 2 O-glycans differentiate colorectal cancer from healthy colon epithelium. 35832079 2 76 theme so-called 217:225 arg1 TACAs 267:271 TACAs 267:271 TACAs 267:271 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 2 76 theme so-called 217:225 arg1 antigens 257:264 The so-called tumor-associated carbohydrate antigens 213:264 The so-called tumor-associated carbohydrate antigens (TACAs) 213:272 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 2 76 theme so-called 217:225 arg1 targets 315:321 promising targets 305:321 promising targets for immunotherapy 305:339 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 5 77 theme O-linked 740:747 arg1 glycans 749:755 the colorectal cancer (CRC)-associated O-linked glycans 701:755 the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts 701:795 Methods: A workflow was established to decode the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts. 35832079 5 78 theme cell 783:786 arg1 extracts 788:795 approximately 20,000 cell extracts 762:795 approximately 20,000 cell extracts 762:795 Methods: A workflow was established to decode the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts. 35832079 12 79 theme colon 1658:1662 arg1 mucosa 1664:1669 normal colon mucosa 1651:1669 normal colon mucosa 1651:1669 In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. 35832079 10 80 theme sialyl- 1461:1467 arg1 antigen 1478:1484 the terminal (sialyl-)LewisX/A antigen 1447:1484 the terminal (sialyl-)LewisX/A antigen 1447:1484 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 13 81 theme TACAs 1853:1857 arg1 panel 1828:1832 a novel panel 1820:1832 a novel panel 1820:1832 Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. 35832079 0 82 theme colon 86:90 arg1 epithelium 92:101 healthy colon epithelium 78:101 healthy colon epithelium 78:101 Specific (sialyl-)Lewis core 2 O-glycans differentiate colorectal cancer from healthy colon epithelium. 35832079 10 83 theme terminal 1451:1458 arg1 antigen 1478:1484 the terminal (sialyl-)LewisX/A antigen 1447:1484 the terminal (sialyl-)LewisX/A antigen 1447:1484 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 8 84 located found 1195:1199 arg1 regions 1248:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 cancerous, stromal and normal colon mucosal regions 1204:1254 Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. 35832079 8 84 located found 1195:1199 arg2 features 1181:1188 Distinctive O-glycosylation features 1153:1188 Distinctive O-glycosylation features 1153:1188 Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. 35832079 12 85 link α2-6-linked 1722:1732 arg1 antigens 1772:1779 α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens 1722:1779 α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens 1722:1779 In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. 35832079 14 86 theme promising 1962:1970 arg1 TACAs 1952:1956 These TACAs 1946:1956 These TACAs 1946:1956 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 14 86 theme promising 1962:1970 arg1 targets 1976:1982 promising new targets 1962:1982 promising new targets for development of innovative cancer immune target therapies 1962:2043 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 9 87 with regions 1310:1316 arg1 absence 1323:1329 absence 1323:1329 absence in normal mucosa 1323:1346 Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. 35832079 3 88 theme malignant 443:451 arg1 phenotype 453:461 the malignant phenotype 439:461 the malignant phenotype of the cancer cells 439:481 These carbohydrates differ from those of the surrounding non-cancerous tissues and contribute to the malignant phenotype of the cancer cells by promoting proliferation, metastasis, and immunosuppression. 35832079 13 89 from differences 1871:1881 arg1 profiles 1899:1906 the glycomic profiles 1886:1906 the glycomic profiles between CRC and healthy colon mucosa 1886:1943 Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. 35832079 10 90 theme LewisX/A 1469:1476 arg1 antigen 1478:1484 the terminal (sialyl-)LewisX/A antigen 1447:1484 the terminal (sialyl-)LewisX/A antigen 1447:1484 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 10 91 theme core 1365:1368 arg1 O-glycans 1372:1380 six core 2 O-glycans 1361:1380 six core 2 O-glycans 1361:1380 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 10 92 located found 1399:1403 arg1 cancers 1429:1435 the cancers 1425:1435 the cancers 1425:1435 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 10 92 located found 1399:1403 arg1 % 1420:1420 more than 33% 1408:1420 more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen 1408:1484 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 10 92 located found 1399:1403 arg2 O-glycans 1372:1380 six core 2 O-glycans 1361:1380 six core 2 O-glycans 1361:1380 From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. 35832079 14 93 theme target 2028:2033 arg1 therapies 2035:2043 innovative cancer immune target therapies 2003:2043 innovative cancer immune target therapies 2003:2043 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 3 94 theme cancer 470:475 arg1 cells 477:481 the cancer cells 466:481 the cancer cells 466:481 These carbohydrates differ from those of the surrounding non-cancerous tissues and contribute to the malignant phenotype of the cancer cells by promoting proliferation, metastasis, and immunosuppression. 35832079 0 95 theme core 24:27 arg1 O-glycans 31:39 Specific (sialyl-)Lewis core 2 O-glycans 0:39 Specific (sialyl-)Lewis core 2 O-glycans 0:39 Specific (sialyl-)Lewis core 2 O-glycans differentiate colorectal cancer from healthy colon epithelium. 35832079 14 96 theme cancer 2014:2019 arg1 therapies 2035:2043 innovative cancer immune target therapies 2003:2043 innovative cancer immune target therapies 2003:2043 These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC. 35832079 11 97 theme cancers 1583:1589 arg1 cancers 1583:1589 the investigated cancers 1566:1589 the investigated cancers 1566:1589 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 11 97 theme cancers 1583:1589 arg1 cancers 1547:1553 the analyzed cancers 1534:1553 the analyzed cancers 1534:1553 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 11 97 theme cancers 1583:1589 arg1 % 1561:1561 94% 1559:1561 94% of the investigated cancers 1559:1589 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 11 97 theme cancers 1583:1589 arg1 % 1529:1529 72% 1527:1529 72% of the analyzed cancers 1527:1553 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 8 98 theme Distinctive 1153:1163 arg1 features 1181:1188 Distinctive O-glycosylation features 1153:1188 Distinctive O-glycosylation features 1153:1188 Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. 35832079 3 99 theme non-cancerous 399:411 arg1 tissues 413:419 the surrounding non-cancerous tissues 383:419 the surrounding non-cancerous tissues 383:419 These carbohydrates differ from those of the surrounding non-cancerous tissues and contribute to the malignant phenotype of the cancer cells by promoting proliferation, metastasis, and immunosuppression. 35832079 6 100 theme fixed 871:875 arg1 tissues 895:901 formalin fixed paraffin embedded tissues 862:901 formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites 862:945 Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. 35832079 9 101 link O-linked 1266:1273 arg1 glycans 1275:1281 Over 100 O-linked glycans 1257:1281 Over 100 O-linked glycans 1257:1281 Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. 35832079 1 102 attach present 184:190 arg1 cells 206:210 neoplastic cells 195:210 neoplastic cells 195:210 Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. 35832079 1 102 attach present 184:190 arg2 carbohydrates 144:156 carbohydrates 144:156 carbohydrates 144:156 Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. 35832079 1 102 attach present 184:190 arg2 some 159:162 some 159:162 some 159:162 Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. 35832079 2 103 theme promising 305:313 arg1 antigens 257:264 The so-called tumor-associated carbohydrate antigens 213:264 The so-called tumor-associated carbohydrate antigens (TACAs) 213:272 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 2 103 theme promising 305:313 arg1 targets 315:321 promising targets 305:321 promising targets for immunotherapy 305:339 The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. 35832079 1 104 theme neoplastic 195:204 arg1 cells 206:210 neoplastic cells 195:210 neoplastic cells 195:210 Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. 35832079 9 105 from absence 1323:1329 arg1 mucosa 1341:1346 normal mucosa 1334:1346 normal mucosa 1334:1346 Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. 35832079 11 106 theme O-glycans 1627:1635 arg1 O-glycans 1627:1635 these two O-glycans 1617:1635 these two O-glycans 1617:1635 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 35832079 11 106 theme O-glycans 1627:1635 arg1 one 1610:1612 one 1610:1612 one 1610:1612 Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. 36160845 3 0 theme Balb/c 470:475 arg1 mice 477:480 Balb/c mice 470:480 Balb/c mice regarding its impact on the intestinal microbiome 470:530 In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. 36160845 4 1 theme anti-inflammatory 840:856 arg1 IL-10 867:871 anti-inflammatory cytokine IL-10 840:871 anti-inflammatory cytokine IL-10 840:871 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 2 theme 2-week 547:552 arg1 administration 559:572 2-week oral administration 547:572 2-week oral administration of DCP 547:579 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 1 3 theme chronic 155:161 arg1 disease 181:187 a chronic inflammatory skin disease 153:187 a chronic inflammatory skin disease with a high prevalence worldwide 153:220 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 1 3 theme chronic 155:161 arg1 dermatitis 134:143 Atopic dermatitis 127:143 Atopic dermatitis (AD) 127:148 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 0 4 theme AD-like 113:119 arg1 mice 121:124 DNFB-induced AD-like mice 100:124 DNFB-induced AD-like mice 100:124 Dendrobium candidum polysaccharide reduce atopic dermatitis symptoms and modulate gut microbiota in DNFB-induced AD-like mice. 36160845 4 5 theme cytokines 755:763 arg1 expression 724:733 the expression 720:733 the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6 720:799 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 5 theme cytokines 755:763 arg1 level 691:695 the level 687:695 the level of serum total IgE 687:714 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 6 theme skin 634:637 arg1 symptoms 598:605 AD-like symptoms 590:605 AD-like symptoms 590:605 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 6 theme skin 634:637 arg1 damage 624:629 histological damage 611:629 histological damage 611:629 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 0 7 theme DNFB-induced 100:111 arg1 mice 121:124 DNFB-induced AD-like mice 100:124 DNFB-induced AD-like mice 100:124 Dendrobium candidum polysaccharide reduce atopic dermatitis symptoms and modulate gut microbiota in DNFB-induced AD-like mice. 36160845 3 8 theme intestinal 510:519 arg1 microbiome 521:530 the intestinal microbiome 506:530 the intestinal microbiome 506:530 In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. 36160845 2 9 theme important 285:293 arg1 role 295:298 an important role 282:298 an important role 282:298 Increasing evidence suggests that the gut microbiota plays an important role in the pathogenesis of AD. 36160845 4 10 theme oral 554:557 arg1 administration 559:572 2-week oral administration 547:572 2-week oral administration of DCP 547:579 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 6 11 theme novel 1087:1091 arg1 DCP 1054:1056 DCP 1054:1056 DCP 1054:1056 Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD. 36160845 6 11 theme novel 1087:1091 arg1 agent 1115:1119 a promising novel microbiota-modulating agent 1075:1119 a promising novel microbiota-modulating agent for the treatment of AD 1075:1143 Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD. 36160845 4 12 theme pro-inflammatory 738:753 arg1 IFN-γ 780:784 IFN-γ 780:784 IFN-γ 780:784 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 12 theme pro-inflammatory 738:753 arg1 cytokines 755:763 pro-inflammatory cytokines 738:763 pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6 738:799 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 12 theme pro-inflammatory 738:753 arg1 TNF-α 773:777 TNF-α 773:777 TNF-α 773:777 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 12 theme pro-inflammatory 738:753 arg1 IL-6 796:799 IL-6 796:799 IL-6 796:799 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 12 theme pro-inflammatory 738:753 arg1 IL-4 787:790 IL-4 787:790 IL-4 787:790 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 1 13 theme inflammatory 163:174 arg1 disease 181:187 a chronic inflammatory skin disease 153:187 a chronic inflammatory skin disease with a high prevalence worldwide 153:220 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 1 13 theme inflammatory 163:174 arg1 dermatitis 134:143 Atopic dermatitis 127:143 Atopic dermatitis (AD) 127:148 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 0 14 theme dermatitis 49:58 arg1 symptoms 60:67 atopic dermatitis symptoms 42:67 atopic dermatitis symptoms 42:67 Dendrobium candidum polysaccharide reduce atopic dermatitis symptoms and modulate gut microbiota in DNFB-induced AD-like mice. 36160845 1 15 theme skin 176:179 arg1 disease 181:187 a chronic inflammatory skin disease 153:187 a chronic inflammatory skin disease with a high prevalence worldwide 153:220 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 1 15 theme skin 176:179 arg1 dermatitis 134:143 Atopic dermatitis 127:143 Atopic dermatitis (AD) 127:148 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 5 16 theme intestinal 944:953 arg1 composition 966:976 the intestinal microbiome composition 940:976 the intestinal microbiome composition 940:976 The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. 36160845 3 17 from effect 366:371 arg1 AD 421:422 AD 421:422 AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome 421:530 In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. 36160845 4 18 theme total 706:710 arg1 IgE 712:714 serum total IgE 700:714 serum total IgE 700:714 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 0 19 theme Dendrobium 0:9 arg1 polysaccharide 20:33 Dendrobium candidum polysaccharide 0:33 Dendrobium candidum polysaccharide 0:33 Dendrobium candidum polysaccharide reduce atopic dermatitis symptoms and modulate gut microbiota in DNFB-induced AD-like mice. 36160845 4 20 theme serum 700:704 arg1 IgE 712:714 serum total IgE 700:714 serum total IgE 700:714 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 5 21 theme DCP 899:901 arg1 effect 889:894 The beneficial effect 874:894 The beneficial effect of DCP 874:901 The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. 36160845 4 22 theme IgE 712:714 arg1 expression 724:733 the expression 720:733 the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6 720:799 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 22 theme IgE 712:714 arg1 level 691:695 the level 687:695 the level of serum total IgE 687:714 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 1 23 theme high 196:199 arg1 worldwide 212:220 a high prevalence worldwide 194:220 a high prevalence worldwide 194:220 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 3 24 theme candidum 387:394 arg1 DCP 413:415 DCP 413:415 DCP 413:415 In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. 36160845 3 24 theme candidum 387:394 arg1 polysaccharides 396:410 Dendrobium candidum polysaccharides 376:410 Dendrobium candidum polysaccharides (DCP) 376:416 In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. 36160845 0 25 from microbiota 86:95 arg1 mice 121:124 DNFB-induced AD-like mice 100:124 DNFB-induced AD-like mice 100:124 Dendrobium candidum polysaccharide reduce atopic dermatitis symptoms and modulate gut microbiota in DNFB-induced AD-like mice. 36160845 1 26 theme prevalence 201:210 arg1 worldwide 212:220 a high prevalence worldwide 194:220 a high prevalence worldwide 194:220 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 0 27 theme atopic 42:47 arg1 symptoms 60:67 atopic dermatitis symptoms 42:67 atopic dermatitis symptoms 42:67 Dendrobium candidum polysaccharide reduce atopic dermatitis symptoms and modulate gut microbiota in DNFB-induced AD-like mice. 36160845 3 28 theme polysaccharides 396:410 arg1 effect 366:371 the effect 362:371 the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome 362:530 In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. 36160845 4 29 theme histological 611:622 arg1 damage 624:629 histological damage 611:629 histological damage 611:629 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 1 30 with disease 181:187 arg1 worldwide 212:220 a high prevalence worldwide 194:220 a high prevalence worldwide 194:220 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 2 31 theme Increasing 223:232 arg1 evidence 234:241 Increasing evidence 223:241 Increasing evidence 223:241 Increasing evidence suggests that the gut microbiota plays an important role in the pathogenesis of AD. 36160845 6 32 used used 1067:1070 arg2 DCP 1054:1056 DCP 1054:1056 DCP 1054:1056 Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD. 36160845 6 32 used used 1067:1070 arg2 agent 1115:1119 a promising novel microbiota-modulating agent 1075:1119 a promising novel microbiota-modulating agent for the treatment of AD 1075:1143 Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD. 36160845 1 33 theme Atopic 127:132 arg1 disease 181:187 a chronic inflammatory skin disease 153:187 a chronic inflammatory skin disease with a high prevalence worldwide 153:220 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 1 33 theme Atopic 127:132 arg1 AD 146:147 AD 146:147 AD 146:147 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 1 33 theme Atopic 127:132 arg1 dermatitis 134:143 Atopic dermatitis 127:143 Atopic dermatitis (AD) 127:148 Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. 36160845 3 34 theme Dendrobium 376:385 arg1 DCP 413:415 DCP 413:415 DCP 413:415 In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. 36160845 3 34 theme Dendrobium 376:385 arg1 polysaccharides 396:410 Dendrobium candidum polysaccharides 376:410 Dendrobium candidum polysaccharides (DCP) 376:416 In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. 36160845 6 35 theme AD 1142:1143 arg1 treatment 1129:1137 the treatment 1125:1137 the treatment of AD 1125:1143 Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD. 36160845 6 36 theme promising 1077:1085 arg1 DCP 1054:1056 DCP 1054:1056 DCP 1054:1056 Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD. 36160845 6 36 theme promising 1077:1085 arg1 agent 1115:1119 a promising novel microbiota-modulating agent 1075:1119 a promising novel microbiota-modulating agent for the treatment of AD 1075:1143 Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD. 36160845 5 37 theme composition 966:976 arg1 unbalance 986:994 the unbalance 982:994 the unbalance of the intestinal homeostasis 982:1024 The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. 36160845 5 37 theme composition 966:976 arg1 restoration 925:935 the restoration 921:935 the restoration of the intestinal microbiome composition 921:976 The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. 36160845 4 38 theme IL-10 867:871 arg1 level 831:835 the expression level 816:835 the expression level of anti-inflammatory cytokine IL-10 816:871 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 5 39 theme intestinal 1003:1012 arg1 homeostasis 1014:1024 the intestinal homeostasis 999:1024 the intestinal homeostasis 999:1024 The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. 36160845 3 40 from 2,4-Dinitrofluorobenzene 435:458 arg1 mice 477:480 Balb/c mice 470:480 Balb/c mice regarding its impact on the intestinal microbiome 470:530 In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. 36160845 5 41 theme beneficial 878:887 arg1 effect 889:894 The beneficial effect 874:894 The beneficial effect of DCP 874:901 The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. 36160845 4 42 theme DCP 577:579 arg1 administration 559:572 2-week oral administration 547:572 2-week oral administration of DCP 547:579 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 43 theme cytokine 858:865 arg1 IL-10 867:871 anti-inflammatory cytokine IL-10 840:871 anti-inflammatory cytokine IL-10 840:871 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 5 44 theme homeostasis 1014:1024 arg1 unbalance 986:994 the unbalance 982:994 the unbalance of the intestinal homeostasis 982:1024 The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. 36160845 5 44 theme homeostasis 1014:1024 arg1 restoration 925:935 the restoration 921:935 the restoration of the intestinal microbiome composition 921:976 The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. 36160845 2 45 theme gut 261:263 arg1 microbiota 265:274 the gut microbiota 257:274 the gut microbiota 257:274 Increasing evidence suggests that the gut microbiota plays an important role in the pathogenesis of AD. 36160845 2 46 theme AD 323:324 arg1 pathogenesis 307:318 the pathogenesis 303:318 the pathogenesis of AD 303:324 Increasing evidence suggests that the gut microbiota plays an important role in the pathogenesis of AD. 36160845 4 47 theme expression 820:829 arg1 level 831:835 the expression level 816:835 the expression level of anti-inflammatory cytokine IL-10 816:871 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 0 48 theme gut 82:84 arg1 microbiota 86:95 gut microbiota 82:95 gut microbiota in DNFB-induced AD-like mice 82:124 Dendrobium candidum polysaccharide reduce atopic dermatitis symptoms and modulate gut microbiota in DNFB-induced AD-like mice. 36160845 5 49 theme microbiome 955:964 arg1 composition 966:976 the intestinal microbiome composition 940:976 the intestinal microbiome composition 940:976 The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. 36160845 4 50 theme cell 653:656 arg1 infiltration 658:669 mast cell infiltration 648:669 mast cell infiltration 648:669 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 4 51 theme AD-like 590:596 arg1 symptoms 598:605 AD-like symptoms 590:605 AD-like symptoms 590:605 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 6 52 theme microbiota-modulating 1093:1113 arg1 DCP 1054:1056 DCP 1054:1056 DCP 1054:1056 Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD. 36160845 6 52 theme microbiota-modulating 1093:1113 arg1 agent 1115:1119 a promising novel microbiota-modulating agent 1075:1119 a promising novel microbiota-modulating agent for the treatment of AD 1075:1143 Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD. 36160845 0 53 dep Dendrobium 0:9 arg1 candidum 11:18 candidum 11:18 candidum 11:18 Dendrobium candidum polysaccharide reduce atopic dermatitis symptoms and modulate gut microbiota in DNFB-induced AD-like mice. 36160845 4 54 theme mast 648:651 arg1 cell 653:656 mast cell 648:656 mast cell infiltration 648:669 We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. 36160845 3 55 from impact 496:501 arg1 microbiome 521:530 the intestinal microbiome 506:530 the intestinal microbiome 506:530 In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. 36010471 2 0 theme original 471:478 arg1 lentinan 480:487 original lentinan 471:487 original lentinan (extracted using hot water) 471:515 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 0 theme original 471:478 arg1 water 510:514 extracted using hot water 490:514 extracted using hot water 490:514 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 1 1 theme immune 314:319 arg1 activity 321:328 immune activity 314:328 immune activity 314:328 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 3 2 theme flexible 865:872 arg1 chain 887:891 a flexible single-helix chain 863:891 a flexible single-helix chain 863:891 Especially at 60, 40/60, and 20/40/60 kHz, according to atomic force microscopy and solution chain conformation parameters, lentinan transformed from a rigid triple-helix chain to a flexible single-helix chain, and the side-chain was severely broken. 36010471 1 3 dep structure 279:287 arg1 the 266:268 the 266:268 the 266:268 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 5 4 theme flexible 1087:1094 arg1 chain 1109:1113 a loose and flexible triple-helix chain 1075:1113 a loose and flexible triple-helix chain 1075:1113 However, at 20/40 and 20/60 kHz, the rigid triple-helix chain transformed into a loose and flexible triple-helix chain, showing the strongest immune activity. 36010471 7 5 theme ultrasound 1478:1487 arg1 potential 1465:1473 the great potential 1455:1473 the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance 1455:1619 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 7 6 theme important 1568:1576 arg1 value 1588:1592 important reference value 1568:1592 important reference value 1568:1592 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 7 7 with potential 1465:1473 arg1 modes 1514:1518 different frequency modes 1494:1518 different frequency modes in carbohydrate food processing, which may have important reference value and practical significance 1494:1619 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 0 8 from edodes 157:162 arg1 Structure 73:81 Structure 73:81 Structure 73:81 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 0 8 from edodes 157:162 arg1 Conformation 90:101 Chain Conformation 84:101 Chain Conformation 84:101 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 0 8 from edodes 157:162 arg1 Polysaccharides 127:141 Polysaccharides 127:141 Polysaccharides from Lentinus edodes 127:162 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 0 8 from edodes 157:162 arg1 Activity 115:122 Immune Activity 108:122 Immune Activity 108:122 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 7 9 from modes 1514:1518 arg1 processing 1541:1550 carbohydrate food processing 1523:1550 carbohydrate food processing 1523:1550 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 0 10 from Effects 0:6 arg1 Structure 73:81 Structure 73:81 Structure 73:81 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 0 10 from Effects 0:6 arg1 Conformation 90:101 Chain Conformation 84:101 Chain Conformation 84:101 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 0 10 from Effects 0:6 arg1 Activity 115:122 Immune Activity 108:122 Immune Activity 108:122 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 2 11 theme monosaccharide 567:580 arg1 composition 582:592 monosaccharide composition 567:592 monosaccharide composition 567:592 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 7 12 theme food 1536:1539 arg1 processing 1541:1550 carbohydrate food processing 1523:1550 carbohydrate food processing 1523:1550 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 1 13 theme frequency 247:255 arg1 modes 257:261 different frequency modes 237:261 different frequency modes 237:261 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 0 14 theme Chain 84:88 arg1 Conformation 90:101 Chain Conformation 84:101 Chain Conformation 84:101 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 1 15 theme lentinan 333:340 arg1 activity 321:328 immune activity 314:328 immune activity 314:328 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 1 15 theme lentinan 333:340 arg1 structure 279:287 chemical structure 270:287 chemical structure 270:287 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 1 15 theme lentinan 333:340 arg1 conformation 296:307 chain conformation 290:307 chain conformation 290:307 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 6 16 theme chain 1322:1326 arg1 characteristics 1288:1302 the conformation characteristics 1271:1302 the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain 1271:1391 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 6 16 theme chain 1322:1326 arg1 side-chain 1382:1391 side-chain 1382:1391 side-chain 1382:1391 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 6 16 theme chain 1322:1326 arg1 stiffness 1351:1359 stiffness 1351:1359 stiffness 1351:1359 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 6 16 theme chain 1322:1326 arg1 number 1343:1348 spiral number 1336:1348 spiral number 1336:1348 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 4 17 theme immune 979:984 arg1 activity 986:993 the worst immune activity 969:993 the worst immune activity 969:993 Under this condition, lentinan had the worst immune activity. 36010471 2 18 theme using 500:504 arg1 lentinan 480:487 original lentinan 471:487 original lentinan (extracted using hot water) 471:515 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 18 theme using 500:504 arg1 water 510:514 extracted using hot water 490:514 extracted using hot water 490:514 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 19 theme lentinan 624:631 arg1 composition 582:592 monosaccharide composition 567:592 monosaccharide composition 567:592 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 19 theme lentinan 624:631 arg1 lentinan 624:631 lentinan 624:631 lentinan 624:631 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 19 theme lentinan 624:631 arg1 groups 614:619 main functional groups 598:619 main functional groups 598:619 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 20 theme extracted 490:498 arg1 lentinan 480:487 original lentinan 471:487 original lentinan (extracted using hot water) 471:515 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 20 theme extracted 490:498 arg1 water 510:514 extracted using hot water 490:514 extracted using hot water 490:514 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 1 21 theme Lentinus 347:354 arg1 edodes 356:361 Lentinus edodes 347:361 Lentinus edodes 347:361 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 4 22 theme worst 973:977 arg1 activity 986:993 the worst immune activity 969:993 the worst immune activity 969:993 Under this condition, lentinan had the worst immune activity. 36010471 6 23 theme immune 1421:1426 arg1 activity 1428:1435 immune activity 1421:1435 immune activity 1421:1435 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 3 24 theme single-helix 874:885 arg1 chain 887:891 a flexible single-helix chain 863:891 a flexible single-helix chain 863:891 Especially at 60, 40/60, and 20/40/60 kHz, according to atomic force microscopy and solution chain conformation parameters, lentinan transformed from a rigid triple-helix chain to a flexible single-helix chain, and the side-chain was severely broken. 36010471 7 25 theme great 1459:1463 arg1 potential 1465:1473 the great potential 1455:1473 the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance 1455:1619 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 2 26 theme functional 603:612 arg1 lentinan 624:631 lentinan 624:631 lentinan 624:631 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 26 theme functional 603:612 arg1 groups 614:619 main functional groups 598:619 main functional groups 598:619 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 27 theme chain 663:667 arg1 conformation 669:680 its chain conformation 659:680 its chain conformation 659:680 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 1 28 from edodes 356:361 arg1 activity 321:328 immune activity 314:328 immune activity 314:328 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 1 28 from edodes 356:361 arg1 structure 279:287 chemical structure 270:287 chemical structure 270:287 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 1 28 from edodes 356:361 arg1 conformation 296:307 chain conformation 290:307 chain conformation 290:307 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 5 29 theme strongest 1128:1136 arg1 activity 1145:1152 the strongest immune activity 1124:1152 the strongest immune activity 1124:1152 However, at 20/40 and 20/60 kHz, the rigid triple-helix chain transformed into a loose and flexible triple-helix chain, showing the strongest immune activity. 36010471 2 30 theme main 598:601 arg1 lentinan 624:631 lentinan 624:631 lentinan 624:631 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 30 theme main 598:601 arg1 groups 614:619 main functional groups 598:619 main functional groups 598:619 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 7 31 theme practical 1598:1606 arg1 significance 1608:1619 practical significance 1598:1619 practical significance 1598:1619 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 0 32 dep Structure 73:81 arg1 the 69:71 the 69:71 the 69:71 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 3 33 theme microscopy 752:761 arg1 parameters 795:804 atomic force microscopy and solution chain conformation parameters 739:804 atomic force microscopy and solution chain conformation parameters 739:804 Especially at 60, 40/60, and 20/40/60 kHz, according to atomic force microscopy and solution chain conformation parameters, lentinan transformed from a rigid triple-helix chain to a flexible single-helix chain, and the side-chain was severely broken. 36010471 6 34 theme important 1403:1411 arg1 role 1413:1416 an important role 1400:1416 an important role 1400:1416 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 0 35 theme Modification 22:33 arg1 Effects 0:6 Effects 0:6 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 0:163 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 5 36 theme immune 1138:1143 arg1 activity 1145:1152 the strongest immune activity 1124:1152 the strongest immune activity 1124:1152 However, at 20/40 and 20/60 kHz, the rigid triple-helix chain transformed into a loose and flexible triple-helix chain, showing the strongest immune activity. 36010471 2 37 theme ultrasonic 527:536 arg1 treatment 538:546 ultrasonic treatment 527:546 ultrasonic treatment 527:546 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 4 38 contain had 965:967 arg2 activity 986:993 the worst immune activity 969:993 the worst immune activity 969:993 Under this condition, lentinan had the worst immune activity. 36010471 4 38 contain had 965:967 arg1 lentinan 956:963 lentinan 956:963 lentinan 956:963 Under this condition, lentinan had the worst immune activity. 36010471 1 39 theme study 181:185 arg1 aim 169:171 The aim 165:171 The aim of this study 165:185 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 0 40 theme Ultrasound 11:20 arg1 Modification 22:33 Ultrasound Modification 11:33 Ultrasound Modification with Different Frequency Modes 11:64 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 1 41 theme chemical 270:277 arg1 structure 279:287 chemical structure 270:287 chemical structure 270:287 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 0 42 theme Immune 108:113 arg1 Activity 115:122 Immune Activity 108:122 Immune Activity 108:122 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 7 43 theme carbohydrate 1523:1534 arg1 processing 1541:1550 carbohydrate food processing 1523:1550 carbohydrate food processing 1523:1550 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 6 44 contain had 1210:1212 arg1 ultrasound 1199:1208 dual-frequency ultrasound 1184:1208 dual-frequency ultrasound 1184:1208 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 6 44 contain had 1210:1212 arg2 effects 1226:1232 significant effects 1214:1232 significant effects 1214:1232 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 0 45 theme Different 40:48 arg1 Modes 60:64 Different Frequency Modes 40:64 Different Frequency Modes 40:64 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 0 46 theme Polysaccharides 127:141 arg1 Structure 73:81 Structure 73:81 Structure 73:81 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 0 46 theme Polysaccharides 127:141 arg1 Conformation 90:101 Chain Conformation 84:101 Chain Conformation 84:101 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 0 46 theme Polysaccharides 127:141 arg1 Activity 115:122 Immune Activity 108:122 Immune Activity 108:122 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 0 47 from Structure 73:81 arg1 edodes 157:162 Lentinus edodes 148:162 Lentinus edodes 148:162 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 6 48 theme significant 1214:1224 arg1 effects 1226:1232 significant effects 1214:1232 significant effects 1214:1232 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 7 49 theme frequency 1504:1512 arg1 modes 1514:1518 different frequency modes 1494:1518 different frequency modes in carbohydrate food processing, which may have important reference value and practical significance 1494:1619 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 3 50 theme force 746:750 arg1 microscopy 752:761 atomic force microscopy 739:761 atomic force microscopy 739:761 Especially at 60, 40/60, and 20/40/60 kHz, according to atomic force microscopy and solution chain conformation parameters, lentinan transformed from a rigid triple-helix chain to a flexible single-helix chain, and the side-chain was severely broken. 36010471 1 51 theme different 237:245 arg1 modes 257:261 different frequency modes 237:261 different frequency modes 237:261 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 1 52 theme structure-activity 368:385 arg1 relationship 387:398 the structure-activity relationship 364:398 the structure-activity relationship of lentinan 364:410 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 0 53 with Modification 22:33 arg1 Modes 60:64 Different Frequency Modes 40:64 Different Frequency Modes 40:64 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 6 54 theme spiral 1336:1341 arg1 number 1343:1348 spiral number 1336:1348 spiral number 1336:1348 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 1 55 theme chain 290:294 arg1 conformation 296:307 chain conformation 290:307 chain conformation 290:307 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 0 56 theme Lentinus 148:155 arg1 edodes 157:162 Lentinus edodes 148:162 Lentinus edodes 148:162 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 5 57 theme triple-helix 1039:1050 arg1 chain 1052:1056 the rigid triple-helix chain 1029:1056 the rigid triple-helix chain 1029:1056 However, at 20/40 and 20/60 kHz, the rigid triple-helix chain transformed into a loose and flexible triple-helix chain, showing the strongest immune activity. 36010471 2 58 theme hot 506:508 arg1 lentinan 480:487 original lentinan 471:487 original lentinan (extracted using hot water) 471:515 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 2 58 theme hot 506:508 arg1 water 510:514 extracted using hot water 490:514 extracted using hot water 490:514 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 0 59 theme Frequency 50:58 arg1 Modes 60:64 Different Frequency Modes 40:64 Different Frequency Modes 40:64 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 5 60 theme loose 1077:1081 arg1 chain 1109:1113 a loose and flexible triple-helix chain 1075:1113 a loose and flexible triple-helix chain 1075:1113 However, at 20/40 and 20/60 kHz, the rigid triple-helix chain transformed into a loose and flexible triple-helix chain, showing the strongest immune activity. 36010471 7 61 theme different 1494:1502 arg1 modes 1514:1518 different frequency modes 1494:1518 different frequency modes in carbohydrate food processing, which may have important reference value and practical significance 1494:1619 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 6 62 theme dual-frequency 1184:1197 arg1 ultrasound 1199:1208 dual-frequency ultrasound 1184:1208 dual-frequency ultrasound 1184:1208 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 5 63 theme rigid 1033:1037 arg1 chain 1052:1056 the rigid triple-helix chain 1029:1056 the rigid triple-helix chain 1029:1056 However, at 20/40 and 20/60 kHz, the rigid triple-helix chain transformed into a loose and flexible triple-helix chain, showing the strongest immune activity. 36010471 3 64 theme rigid 835:839 arg1 chain 854:858 a rigid triple-helix chain 833:858 a rigid triple-helix chain to a flexible single-helix chain 833:891 Especially at 60, 40/60, and 20/40/60 kHz, according to atomic force microscopy and solution chain conformation parameters, lentinan transformed from a rigid triple-helix chain to a flexible single-helix chain, and the side-chain was severely broken. 36010471 3 65 theme atomic 739:744 arg1 microscopy 752:761 atomic force microscopy 739:761 atomic force microscopy 739:761 Especially at 60, 40/60, and 20/40/60 kHz, according to atomic force microscopy and solution chain conformation parameters, lentinan transformed from a rigid triple-helix chain to a flexible single-helix chain, and the side-chain was severely broken. 36010471 6 66 theme conformation 1275:1286 arg1 characteristics 1288:1302 the conformation characteristics 1271:1302 the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain 1271:1391 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 6 66 theme conformation 1275:1286 arg1 side-chain 1382:1391 side-chain 1382:1391 side-chain 1382:1391 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 6 66 theme conformation 1275:1286 arg1 stiffness 1351:1359 stiffness 1351:1359 stiffness 1351:1359 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 6 66 theme conformation 1275:1286 arg1 number 1343:1348 spiral number 1336:1348 spiral number 1336:1348 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 1 67 theme lentinan 403:410 arg1 relationship 387:398 the structure-activity relationship 364:398 the structure-activity relationship of lentinan 364:410 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 6 68 theme polysaccharide 1307:1320 arg1 chain 1322:1326 polysaccharide chain 1307:1326 polysaccharide chain 1307:1326 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 3 69 theme triple-helix 841:852 arg1 chain 854:858 a rigid triple-helix chain 833:858 a rigid triple-helix chain to a flexible single-helix chain 833:891 Especially at 60, 40/60, and 20/40/60 kHz, according to atomic force microscopy and solution chain conformation parameters, lentinan transformed from a rigid triple-helix chain to a flexible single-helix chain, and the side-chain was severely broken. 36010471 3 70 theme chain 776:780 arg1 conformation 782:793 solution chain conformation 767:793 solution chain conformation 767:793 Especially at 60, 40/60, and 20/40/60 kHz, according to atomic force microscopy and solution chain conformation parameters, lentinan transformed from a rigid triple-helix chain to a flexible single-helix chain, and the side-chain was severely broken. 36010471 1 71 from effects 210:216 arg1 activity 321:328 immune activity 314:328 immune activity 314:328 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 1 71 from effects 210:216 arg1 structure 279:287 chemical structure 270:287 chemical structure 270:287 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 1 71 from effects 210:216 arg1 conformation 296:307 chain conformation 290:307 chain conformation 290:307 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 0 72 from Conformation 90:101 arg1 edodes 157:162 Lentinus edodes 148:162 Lentinus edodes 148:162 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 7 73 contain have 1563:1566 arg2 value 1588:1592 important reference value 1568:1592 important reference value 1568:1592 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 7 73 contain have 1563:1566 arg1 processing 1541:1550 carbohydrate food processing 1523:1550 carbohydrate food processing 1523:1550 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 7 73 contain have 1563:1566 arg2 significance 1608:1619 practical significance 1598:1619 practical significance 1598:1619 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 3 74 theme conformation 782:793 arg1 parameters 795:804 atomic force microscopy and solution chain conformation parameters 739:804 atomic force microscopy and solution chain conformation parameters 739:804 Especially at 60, 40/60, and 20/40/60 kHz, according to atomic force microscopy and solution chain conformation parameters, lentinan transformed from a rigid triple-helix chain to a flexible single-helix chain, and the side-chain was severely broken. 36010471 5 75 theme triple-helix 1096:1107 arg1 chain 1109:1113 a loose and flexible triple-helix chain 1075:1113 a loose and flexible triple-helix chain 1075:1113 However, at 20/40 and 20/60 kHz, the rigid triple-helix chain transformed into a loose and flexible triple-helix chain, showing the strongest immune activity. 36010471 1 76 with ultrasound 221:230 arg1 modes 257:261 different frequency modes 237:261 different frequency modes 237:261 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 36010471 0 77 from Activity 115:122 arg1 edodes 157:162 Lentinus edodes 148:162 Lentinus edodes 148:162 Effects of Ultrasound Modification with Different Frequency Modes on the Structure, Chain Conformation, and Immune Activity of Polysaccharides from Lentinus edodes. 36010471 2 78 dep composition 582:592 arg1 the 563:565 the 563:565 the 563:565 The results showed that, compared with original lentinan (extracted using hot water), although ultrasonic treatment did not change the monosaccharide composition and main functional groups of lentinan, it significantly changed its chain conformation. 36010471 3 79 theme solution 767:774 arg1 conformation 782:793 solution chain conformation 767:793 solution chain conformation 767:793 Especially at 60, 40/60, and 20/40/60 kHz, according to atomic force microscopy and solution chain conformation parameters, lentinan transformed from a rigid triple-helix chain to a flexible single-helix chain, and the side-chain was severely broken. 36010471 7 80 theme reference 1578:1586 arg1 value 1588:1592 important reference value 1568:1592 important reference value 1568:1592 This study shows the great potential of ultrasound with different frequency modes in carbohydrate food processing, which may have important reference value and practical significance. 36010471 6 81 theme lentinan 1257:1264 arg1 conformation 1241:1252 the conformation 1237:1252 the conformation of lentinan 1237:1264 These results indicated that dual-frequency ultrasound had significant effects on the conformation of lentinan, and the conformation characteristics of polysaccharide chain such as spiral number, stiffness and flexibility, and side-chain played an important role in immune activity. 36010471 1 82 theme ultrasound 221:230 arg1 effects 210:216 the effects 206:216 the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes 206:361 The aim of this study was to investigate the effects of ultrasound with different frequency modes on the chemical structure, chain conformation, and immune activity of lentinan from Lentinus edodes; the structure-activity relationship of lentinan was also discussed. 37141316 8 0 theme divergent 1148:1156 arg1 synteny 1158:1164 divergent synteny 1148:1164 divergent synteny 1148:1164 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 4 1 theme gene 561:564 arg1 diversity 566:574 phylogenetic gene diversity 548:574 phylogenetic gene diversity 548:574 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 5 2 theme genes 642:646 arg1 differentiation 613:627 a profound genomic differentiation 594:627 a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups 594:747 Results revealed a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups. 37141316 6 3 theme number 793:798 arg1 patterns 771:778 overall patterns 763:778 overall patterns of gene copy number variation and synteny 763:820 For example, overall patterns of gene copy number variation and synteny were clearly divergent between Poaceae and eudicot species. 37141316 9 4 theme Poaceae 1702:1708 arg1 walls 1715:1719 Poaceae cell walls 1702:1719 Poaceae cell walls 1702:1719 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 6 5 theme gene 783:786 arg1 number 793:798 gene copy number variation and synteny 783:820 number 793:798 For example, overall patterns of gene copy number variation and synteny were clearly divergent between Poaceae and eudicot species. 37141316 8 6 theme major 1240:1244 arg1 genes 1259:1263 the major biosynthetic genes 1236:1263 the major biosynthetic genes of xyloglucans, mannans, and xylans 1236:1299 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 9 7 located observed 1690:1697 arg2 compounds 1680:1688 phenylpropanoid compounds 1664:1688 phenylpropanoid compounds observed in Poaceae cell walls 1664:1719 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 9 7 located observed 1690:1697 arg1 walls 1715:1719 Poaceae cell walls 1702:1719 Poaceae cell walls 1702:1719 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 5 8 theme cell 632:635 arg1 genes 642:646 cell wall genes 632:646 cell wall genes 632:646 Results revealed a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups. 37141316 10 9 theme biological 1814:1823 arg1 relevance 1825:1833 their evolutionary and biological relevance 1791:1833 their evolutionary and biological relevance for cell wall (genomic) diversification between Poaceae and eudicots 1791:1902 All these patterns are discussed in detail in this study, along with their evolutionary and biological relevance for cell wall (genomic) diversification between Poaceae and eudicots. 37141316 9 10 theme Poaceae-specific 1466:1481 arg1 clusters 1490:1497 Poaceae-specific tandem clusters 1466:1497 Poaceae-specific tandem clusters 1466:1497 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 8 11 theme gene 1197:1200 arg1 diversification 1202:1216 phylogenetic gene diversification 1184:1216 phylogenetic gene diversification 1184:1216 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 8 12 theme xyloglucans 1268:1278 arg1 genes 1259:1263 the major biosynthetic genes 1236:1263 the major biosynthetic genes of xyloglucans, mannans, and xylans 1236:1299 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 10 13 theme evolutionary 1797:1808 arg1 relevance 1825:1833 their evolutionary and biological relevance 1791:1833 their evolutionary and biological relevance for cell wall (genomic) diversification between Poaceae and eudicots 1791:1902 All these patterns are discussed in detail in this study, along with their evolutionary and biological relevance for cell wall (genomic) diversification between Poaceae and eudicots. 37141316 8 14 theme mannans 1281:1287 arg1 genes 1259:1263 the major biosynthetic genes 1236:1263 the major biosynthetic genes of xyloglucans, mannans, and xylans 1236:1299 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 5 15 theme cell 702:705 arg1 diversity 712:720 the cell wall diversity 698:720 the cell wall diversity between these plant groups 698:747 Results revealed a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups. 37141316 10 16 theme wall 1844:1847 arg1 diversification 1859:1873 cell wall (genomic) diversification 1839:1873 cell wall (genomic) diversification between Poaceae and eudicots 1839:1902 All these patterns are discussed in detail in this study, along with their evolutionary and biological relevance for cell wall (genomic) diversification between Poaceae and eudicots. 37141316 7 17 theme HOMEODOMAIN 1007:1017 arg1 pathway 1032:1038 the BEL1-like HOMEODOMAIN 6 regulatory pathway 993:1038 the BEL1-like HOMEODOMAIN 6 regulatory pathway 993:1038 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 9 18 theme higher 1506:1511 arg1 number 1518:1523 higher copy number 1506:1523 higher copy number 1506:1523 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 9 19 theme PHENYLALANINE 1528:1540 arg1 AMMONIA-LYASE 1542:1554 PHENYLALANINE AMMONIA-LYASE 1528:1554 PHENYLALANINE AMMONIA-LYASE 1528:1554 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 10 20 theme genomic 1850:1856 arg1 diversification 1859:1873 cell wall (genomic) diversification 1839:1873 cell wall (genomic) diversification between Poaceae and eudicots 1839:1902 All these patterns are discussed in detail in this study, along with their evolutionary and biological relevance for cell wall (genomic) diversification between Poaceae and eudicots. 37141316 4 21 theme copy 486:489 arg1 number 491:496 copy number 486:496 copy number 486:496 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 0 22 theme Poaceae 78:84 arg1 walls 69:73 the different cell walls 50:73 the different cell walls of Poaceae and eudicots 50:97 Highly differentiated genomic properties underpin the different cell walls of Poaceae and eudicots. 37141316 9 23 theme ACID 1565:1568 arg1 O-METHYLTRANSFERASE 1570:1588 CAFFEIC ACID O-METHYLTRANSFERASE 1557:1588 CAFFEIC ACID O-METHYLTRANSFERASE 1557:1588 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 1 24 dep differ 141:146 arg1 both 163:166 both 163:166 both 163:166 Plant cell walls of Poaceae and eudicots differ substantially, both in the content and composition of their components. 37141316 0 25 theme eudicots 90:97 arg1 walls 69:73 the different cell walls 50:73 the different cell walls of Poaceae and eudicots 50:97 Highly differentiated genomic properties underpin the different cell walls of Poaceae and eudicots. 37141316 3 26 theme angiosperm 411:420 arg1 genomes 422:428 169 angiosperm genomes 407:428 169 angiosperm genomes 407:428 In this research, we analyzed multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes. 37141316 9 27 theme PEROXIDASE 1594:1603 arg1 genes 1605:1609 PEROXIDASE genes 1594:1609 PEROXIDASE genes 1594:1609 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 7 28 theme copy 921:924 arg1 number 926:931 differential Poaceae-eudicot copy number 892:931 differential Poaceae-eudicot copy number 892:931 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 7 29 theme wall 1097:1100 arg1 synthesis 1102:1110 secondary cell wall synthesis 1082:1110 secondary cell wall synthesis in Poaceae and eudicots 1082:1134 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 3 30 theme genomic 350:356 arg1 properties 358:367 multiple genomic properties 341:367 multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes 341:428 In this research, we analyzed multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes. 37141316 4 31 theme gene 529:532 arg1 clusters 534:541 tandem gene clusters 522:541 tandem gene clusters 522:541 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 8 32 theme polysaccharides 1385:1399 arg1 differences 1401:1411 hemicellulosic polysaccharides differences 1370:1411 hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls 1370:1445 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 0 33 theme genomic 22:28 arg1 properties 30:39 Highly differentiated genomic properties 0:39 Highly differentiated genomic properties 0:39 Highly differentiated genomic properties underpin the different cell walls of Poaceae and eudicots. 37141316 1 34 theme cell 106:109 arg1 walls 111:115 Plant cell walls 100:115 Plant cell walls of Poaceae and eudicots 100:139 Plant cell walls of Poaceae and eudicots differ substantially, both in the content and composition of their components. 37141316 1 35 theme eudicots 132:139 arg1 walls 111:115 Plant cell walls 100:115 Plant cell walls of Poaceae and eudicots 100:139 Plant cell walls of Poaceae and eudicots differ substantially, both in the content and composition of their components. 37141316 3 36 theme gene 386:389 arg1 families 391:398 150 cell wall gene families 372:398 150 cell wall gene families across 169 angiosperm genomes 372:428 In this research, we analyzed multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes. 37141316 7 37 from synthesis 1102:1110 arg1 Poaceae 1115:1121 Poaceae 1115:1121 Poaceae 1115:1121 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 7 37 from synthesis 1102:1110 arg1 eudicots 1127:1134 eudicots 1127:1134 eudicots 1127:1134 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 3 38 theme cell 376:379 arg1 families 391:398 150 cell wall gene families 372:398 150 cell wall gene families across 169 angiosperm genomes 372:428 In this research, we analyzed multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes. 37141316 0 39 theme different 54:62 arg1 walls 69:73 the different cell walls 50:73 the different cell walls of Poaceae and eudicots 50:97 Highly differentiated genomic properties underpin the different cell walls of Poaceae and eudicots. 37141316 9 40 theme larger 1646:1651 arg1 variety 1653:1659 larger variety 1646:1659 larger variety of phenylpropanoid compounds observed in Poaceae cell walls 1646:1719 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 9 40 theme larger 1646:1651 arg1 compounds 1680:1688 phenylpropanoid compounds 1664:1688 phenylpropanoid compounds observed in Poaceae cell walls 1664:1719 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 8 41 theme cell 1436:1439 arg1 walls 1441:1445 eudicot cell walls 1428:1445 eudicot cell walls 1428:1445 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 1 42 dep content 175:181 arg1 the 171:173 the 171:173 the 171:173 Plant cell walls of Poaceae and eudicots differ substantially, both in the content and composition of their components. 37141316 8 43 from content 1349:1355 arg1 Poaceae 1416:1422 Poaceae 1416:1422 Poaceae 1416:1422 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 8 43 from content 1349:1355 arg1 walls 1441:1445 eudicot cell walls 1428:1445 eudicot cell walls 1428:1445 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 1 44 theme components 208:217 arg1 composition 187:197 composition 187:197 composition 187:197 Plant cell walls of Poaceae and eudicots differ substantially, both in the content and composition of their components. 37141316 1 44 theme components 208:217 arg1 content 175:181 content 175:181 content 175:181 Plant cell walls of Poaceae and eudicots differ substantially, both in the content and composition of their components. 37141316 8 45 from differences 1334:1344 arg1 content 1349:1355 content 1349:1355 content 1349:1355 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 8 45 from differences 1334:1344 arg1 types 1361:1365 types 1361:1365 types 1361:1365 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 9 46 theme compounds 1680:1688 arg1 content 1634:1640 the higher content 1623:1640 the higher content 1623:1640 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 9 46 theme compounds 1680:1688 arg1 variety 1653:1659 larger variety 1646:1659 larger variety of phenylpropanoid compounds observed in Poaceae cell walls 1646:1719 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 9 46 theme compounds 1680:1688 arg1 compounds 1680:1688 phenylpropanoid compounds 1664:1688 phenylpropanoid compounds observed in Poaceae cell walls 1664:1719 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 5 47 theme wall 637:640 arg1 genes 642:646 cell wall genes 632:646 cell wall genes 632:646 Results revealed a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups. 37141316 4 48 theme phylogenetic 548:559 arg1 diversity 566:574 phylogenetic gene diversity 548:574 phylogenetic gene diversity 548:574 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 6 49 theme copy 788:791 arg1 number 793:798 gene copy number variation and synteny 783:820 number 793:798 For example, overall patterns of gene copy number variation and synteny were clearly divergent between Poaceae and eudicot species. 37141316 8 50 from types 1361:1365 arg1 Poaceae 1416:1422 Poaceae 1416:1422 Poaceae 1416:1422 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 8 50 from types 1361:1365 arg1 walls 1441:1445 eudicot cell walls 1428:1445 eudicot cell walls 1428:1445 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 9 51 theme cell 1710:1713 arg1 walls 1715:1719 Poaceae cell walls 1702:1719 Poaceae cell walls 1702:1719 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 5 52 theme genomic 605:611 arg1 differentiation 613:627 a profound genomic differentiation 594:627 a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups 594:747 Results revealed a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups. 37141316 8 53 from Poaceae 1416:1422 arg1 content 1349:1355 content 1349:1355 content 1349:1355 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 8 53 from Poaceae 1416:1422 arg1 types 1361:1365 types 1361:1365 types 1361:1365 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 8 54 theme copy 1167:1170 arg1 number 1172:1177 copy number 1167:1177 copy number 1167:1177 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 6 55 theme eudicot 865:871 arg1 species 873:879 eudicot species 865:879 eudicot species 865:879 For example, overall patterns of gene copy number variation and synteny were clearly divergent between Poaceae and eudicot species. 37141316 7 56 theme secondary 1082:1090 arg1 synthesis 1102:1110 secondary cell wall synthesis 1082:1110 secondary cell wall synthesis in Poaceae and eudicots 1082:1134 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 6 57 theme overall 763:769 arg1 patterns 771:778 overall patterns 763:778 overall patterns of gene copy number variation and synteny 763:820 For example, overall patterns of gene copy number variation and synteny were clearly divergent between Poaceae and eudicot species. 37141316 8 58 from differences 1401:1411 arg1 Poaceae 1416:1422 Poaceae 1416:1422 Poaceae 1416:1422 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 8 58 from differences 1401:1411 arg1 walls 1441:1445 eudicot cell walls 1428:1445 eudicot cell walls 1428:1445 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 7 59 theme cell 1092:1095 arg1 synthesis 1102:1110 secondary cell wall synthesis 1082:1110 secondary cell wall synthesis in Poaceae and eudicots 1082:1134 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 8 60 theme biosynthetic 1246:1257 arg1 genes 1259:1263 the major biosynthetic genes 1236:1263 the major biosynthetic genes of xyloglucans, mannans, and xylans 1236:1299 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 8 61 from walls 1441:1445 arg1 content 1349:1355 content 1349:1355 content 1349:1355 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 8 61 from walls 1441:1445 arg1 types 1361:1365 types 1361:1365 types 1361:1365 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 9 62 theme tandem 1483:1488 arg1 clusters 1490:1497 Poaceae-specific tandem clusters 1466:1497 Poaceae-specific tandem clusters 1466:1497 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 8 63 theme phylogenetic 1184:1195 arg1 diversification 1202:1216 phylogenetic gene diversification 1184:1216 phylogenetic gene diversification 1184:1216 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 6 64 dep number 793:798 arg1 variation 800:808 variation 800:808 variation 800:808 For example, overall patterns of gene copy number variation and synteny were clearly divergent between Poaceae and eudicot species. 37141316 10 65 theme cell 1839:1842 arg1 diversification 1859:1873 cell wall (genomic) diversification 1839:1873 cell wall (genomic) diversification between Poaceae and eudicots 1839:1902 All these patterns are discussed in detail in this study, along with their evolutionary and biological relevance for cell wall (genomic) diversification between Poaceae and eudicots. 37141316 9 66 theme copy 1513:1516 arg1 number 1518:1523 higher copy number 1506:1523 higher copy number 1506:1523 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 7 67 theme regulatory 1021:1030 arg1 pathway 1032:1038 the BEL1-like HOMEODOMAIN 6 regulatory pathway 993:1038 the BEL1-like HOMEODOMAIN 6 regulatory pathway 993:1038 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 2 68 theme genetic 245:251 arg1 basis 253:257 the genomic and genetic basis 229:257 the genomic and genetic basis underlying these differences 229:286 However, the genomic and genetic basis underlying these differences is not fully resolved. 37141316 7 69 theme BEL1-like 997:1005 arg1 pathway 1032:1038 the BEL1-like HOMEODOMAIN 6 regulatory pathway 993:1038 the BEL1-like HOMEODOMAIN 6 regulatory pathway 993:1038 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 1 70 theme Poaceae 120:126 arg1 walls 111:115 Plant cell walls 100:115 Plant cell walls of Poaceae and eudicots 100:139 Plant cell walls of Poaceae and eudicots differ substantially, both in the content and composition of their components. 37141316 8 71 theme xylans 1294:1299 arg1 genes 1259:1263 the major biosynthetic genes 1236:1263 the major biosynthetic genes of xyloglucans, mannans, and xylans 1236:1299 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 5 72 theme plant 736:740 arg1 groups 742:747 these plant groups 730:747 these plant groups 730:747 Results revealed a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups. 37141316 2 73 theme genomic 233:239 arg1 basis 253:257 the genomic and genetic basis 229:257 the genomic and genetic basis underlying these differences 229:286 However, the genomic and genetic basis underlying these differences is not fully resolved. 37141316 9 74 theme AMMONIA-LYASE 1542:1554 arg1 clusters 1490:1497 Poaceae-specific tandem clusters 1466:1497 Poaceae-specific tandem clusters 1466:1497 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 7 75 theme Poaceae-eudicot 905:919 arg1 number 926:931 differential Poaceae-eudicot copy number 892:931 differential Poaceae-eudicot copy number 892:931 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 9 76 theme CAFFEIC 1557:1563 arg1 ACID 1565:1568 CAFFEIC ACID 1557:1568 CAFFEIC ACID O-METHYLTRANSFERASE 1557:1588 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 5 77 theme wall 707:710 arg1 diversity 712:720 the cell wall diversity 698:720 the cell wall diversity between these plant groups 698:747 Results revealed a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups. 37141316 9 78 theme O-METHYLTRANSFERASE 1570:1588 arg1 clusters 1490:1497 Poaceae-specific tandem clusters 1466:1497 Poaceae-specific tandem clusters 1466:1497 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 3 79 theme multiple 341:348 arg1 properties 358:367 multiple genomic properties 341:367 multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes 341:428 In this research, we analyzed multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes. 37141316 4 80 theme gene 463:466 arg1 presence/absence 468:483 gene presence/absence 463:483 gene presence/absence 463:483 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 5 81 theme profound 596:603 arg1 differentiation 613:627 a profound genomic differentiation 594:627 a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups 594:747 Results revealed a profound genomic differentiation of cell wall genes between Poaceae and eudicots, often associated to the cell wall diversity between these plant groups. 37141316 0 82 theme differentiated 7:20 arg1 properties 30:39 Highly differentiated genomic properties 0:39 Highly differentiated genomic properties 0:39 Highly differentiated genomic properties underpin the different cell walls of Poaceae and eudicots. 37141316 7 83 theme genomic 937:943 arg1 contexts 945:952 genomic contexts 937:952 genomic contexts 937:952 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 9 84 theme genes 1605:1609 arg1 clusters 1490:1497 Poaceae-specific tandem clusters 1466:1497 Poaceae-specific tandem clusters 1466:1497 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 4 85 theme clusters 534:541 arg1 presence/absence 468:483 gene presence/absence 463:483 gene presence/absence 463:483 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 4 85 theme clusters 534:541 arg1 number 491:496 copy number 486:496 copy number 486:496 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 4 85 theme clusters 534:541 arg1 diversity 566:574 phylogenetic gene diversity 548:574 phylogenetic gene diversity 548:574 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 4 85 theme clusters 534:541 arg1 occurrence 508:517 occurrence 508:517 occurrence of tandem gene clusters 508:541 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 4 85 theme clusters 534:541 arg1 synteny 499:505 synteny 499:505 synteny 499:505 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 1 86 theme Plant 100:104 arg1 walls 111:115 Plant cell walls 100:115 Plant cell walls of Poaceae and eudicots 100:139 Plant cell walls of Poaceae and eudicots differ substantially, both in the content and composition of their components. 37141316 8 87 theme hemicellulosic 1370:1383 arg1 differences 1401:1411 hemicellulosic polysaccharides differences 1370:1411 hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls 1370:1445 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 9 88 theme higher 1627:1632 arg1 content 1634:1640 the higher content 1623:1640 the higher content 1623:1640 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 3 89 theme families 391:398 arg1 properties 358:367 multiple genomic properties 341:367 multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes 341:428 In this research, we analyzed multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes. 37141316 8 90 theme differences 1401:1411 arg1 content 1349:1355 content 1349:1355 content 1349:1355 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 8 90 theme differences 1401:1411 arg1 types 1361:1365 types 1361:1365 types 1361:1365 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 0 91 theme cell 64:67 arg1 walls 69:73 the different cell walls 50:73 the different cell walls of Poaceae and eudicots 50:97 Highly differentiated genomic properties underpin the different cell walls of Poaceae and eudicots. 37141316 3 92 theme wall 381:384 arg1 families 391:398 150 cell wall gene families 372:398 150 cell wall gene families across 169 angiosperm genomes 372:428 In this research, we analyzed multiple genomic properties of 150 cell wall gene families across 169 angiosperm genomes. 37141316 4 93 theme tandem 522:527 arg1 clusters 534:541 tandem gene clusters 522:541 tandem gene clusters 522:541 The properties analyzed include gene presence/absence, copy number, synteny, occurrence of tandem gene clusters, and phylogenetic gene diversity. 37141316 7 94 theme differential 892:903 arg1 number 926:931 differential Poaceae-eudicot copy number 892:931 differential Poaceae-eudicot copy number 892:931 Moreover, differential Poaceae-eudicot copy number and genomic contexts were observed for all the genes within the BEL1-like HOMEODOMAIN 6 regulatory pathway, which respectively induces and represses secondary cell wall synthesis in Poaceae and eudicots. 37141316 6 95 theme synteny 814:820 arg1 patterns 771:778 overall patterns 763:778 overall patterns of gene copy number variation and synteny 763:820 For example, overall patterns of gene copy number variation and synteny were clearly divergent between Poaceae and eudicot species. 37141316 8 96 theme eudicot 1428:1434 arg1 walls 1441:1445 eudicot cell walls 1428:1445 eudicot cell walls 1428:1445 Similarly, divergent synteny, copy number, and phylogenetic gene diversification were observed for the major biosynthetic genes of xyloglucans, mannans, and xylans, potentially contributing to the differences in content and types of hemicellulosic polysaccharides differences in Poaceae and eudicot cell walls. 37141316 9 97 theme phenylpropanoid 1664:1678 arg1 compounds 1680:1688 phenylpropanoid compounds 1664:1688 phenylpropanoid compounds observed in Poaceae cell walls 1664:1719 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 37141316 9 98 dep clusters 1490:1497 arg1 the 1462:1464 the 1462:1464 the 1462:1464 Additionally, the Poaceae-specific tandem clusters and/or higher copy number of PHENYLALANINE AMMONIA-LYASE, CAFFEIC ACID O-METHYLTRANSFERASE, or PEROXIDASE genes may underly the higher content and larger variety of phenylpropanoid compounds observed in Poaceae cell walls. 36901814 5 0 theme TiO2 1013:1016 arg1 particles 1018:1026 the TiO2 particles suspension (removal efficiency between 68% and 75%) 1009:1078 the TiO2 particles suspension (removal efficiency between 68% and 75%) 1009:1078 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 0 1 theme Oxides 74:79 arg1 Removal 52:58 Removal 52:58 Removal of Some Metal Oxides from Simulated Wastewater 52:105 Cationic Pullulan Derivatives Based Flocculants for Removal of Some Metal Oxides from Simulated Wastewater. 36901814 1 2 from flocculants 164:174 arg1 treatment 190:198 wastewater treatment 179:198 wastewater treatment due to their non-toxicity, low price, biodegradability, etc 179:258 Modified polysaccharides have been increasingly used as flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc. 36901814 4 3 theme pH 694:695 arg1 influence 584:592 The influence 580:592 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy 580:779 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 8 4 theme mixture 1452:1458 arg1 particles 1460:1468 the Bordeaux mixture particles 1439:1468 the Bordeaux mixture particles 1439:1468 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 6 5 theme aggregates 1134:1143 arg1 size 1145:1148 the particle aggregates size 1121:1148 the particle aggregates size 1121:1148 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 5 6 theme TMAP 874:877 arg1 efficacy 862:869 a very good removal efficacy 842:869 a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics 842:981 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 4 7 theme ionic 609:613 arg1 content 615:621 the polymer ionic content 597:621 the polymer ionic content 597:621 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 0 8 theme Simulated 86:94 arg1 Wastewater 96:105 Simulated Wastewater 86:105 Simulated Wastewater 86:105 Cationic Pullulan Derivatives Based Flocculants for Removal of Some Metal Oxides from Simulated Wastewater. 36901814 8 9 theme simulated 1475:1483 arg1 wastewater 1485:1494 simulated wastewater 1475:1494 simulated wastewater 1475:1494 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 6 10 theme potential 1107:1115 arg1 measurements 1150:1161 Both the zeta potential and the particle aggregates size measurements 1093:1161 Both the zeta potential and the particle aggregates size measurements 1093:1161 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 4 11 dep pH 694:695 arg1 salts 735:739 salts 735:739 salts 735:739 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 4 11 dep pH 694:695 arg1 kaolin 746:751 kaolin 746:751 kaolin 746:751 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 4 11 dep pH 694:695 arg1 the 679:681 the 679:681 the 679:681 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 4 11 dep pH 694:695 arg1 content 726:732 metal oxide content 714:732 metal oxide content 714:732 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 3 12 theme quaternary 495:504 arg1 chloride 563:570 trimethylammonium propyl carbamate chloride 528:570 trimethylammonium propyl carbamate chloride (TMAP) 528:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 12 theme quaternary 495:504 arg1 groups 520:525 pendant quaternary ammonium salt groups 487:525 pendant quaternary ammonium salt groups 487:525 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 0 13 from Removal 52:58 arg1 Wastewater 96:105 Simulated Wastewater 86:105 Simulated Wastewater 86:105 Cationic Pullulan Derivatives Based Flocculants for Removal of Some Metal Oxides from Simulated Wastewater. 36901814 6 14 theme main 1196:1199 arg1 patch 1183:1187 the charge patch 1172:1187 the charge patch 1172:1187 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 6 14 theme main 1196:1199 arg1 mechanism 1201:1209 the main mechanism 1192:1209 the main mechanism which governs the metal oxide removal process 1192:1255 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 4 15 from influence 584:592 arg1 efficacy 772:779 the separation efficacy 757:779 the separation efficacy 757:779 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 2 16 theme pullulan 274:281 arg1 derivatives 283:293 the pullulan derivatives 270:293 the pullulan derivatives 270:293 However, the pullulan derivatives are less used in wastewater purification processes. 36901814 1 17 theme wastewater 179:188 arg1 treatment 190:198 wastewater treatment 179:198 wastewater treatment due to their non-toxicity, low price, biodegradability, etc 179:258 Modified polysaccharides have been increasingly used as flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc. 36901814 4 18 theme polymer 601:607 arg1 content 615:621 the polymer ionic content 597:621 the polymer ionic content 597:621 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 1 19 used used 156:159 arg2 polysaccharides 117:131 Modified polysaccharides 108:131 Modified polysaccharides 108:131 Modified polysaccharides have been increasingly used as flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc. 36901814 1 19 used used 156:159 arg2 flocculants 164:174 flocculants 164:174 flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc 164:258 Modified polysaccharides have been increasingly used as flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc. 36901814 5 20 theme irrespective 924:935 arg1 particles 891:899 the FeO particles 883:899 the FeO particles (around 95% and more) 883:921 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 5 21 theme good 849:852 arg1 efficacy 862:869 a very good removal efficacy 842:869 a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics 842:981 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 0 22 theme Pullulan 9:16 arg1 Derivatives 18:28 Cationic Pullulan Derivatives 0:28 Cationic Pullulan Derivatives 0:28 Cationic Pullulan Derivatives Based Flocculants for Removal of Some Metal Oxides from Simulated Wastewater. 36901814 8 23 theme removal 1372:1378 arg1 efficiency 1380:1389 A good removal efficiency 1365:1389 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater 1365:1494 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 8 23 theme removal 1372:1378 arg1 % 1394:1394 90% 1392:1394 90% 1392:1394 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 2 24 theme wastewater 312:321 arg1 processes 336:344 wastewater purification processes 312:344 wastewater purification processes 312:344 However, the pullulan derivatives are less used in wastewater purification processes. 36901814 5 25 theme removal 854:860 arg1 efficacy 862:869 a very good removal efficacy 842:869 a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics 842:981 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 0 26 theme Cationic 0:7 arg1 Derivatives 18:28 Cationic Pullulan Derivatives 0:28 Cationic Pullulan Derivatives 0:28 Cationic Pullulan Derivatives Based Flocculants for Removal of Some Metal Oxides from Simulated Wastewater. 36901814 4 27 theme metal 714:718 arg1 content 726:732 metal oxide content 714:732 metal oxide content 714:732 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 7 28 theme supplementary 1308:1320 arg1 evidence 1322:1329 supplementary evidence 1308:1329 supplementary evidence regarding the separation process 1308:1362 The surface morphology analysis/EDX data provided supplementary evidence regarding the separation process. 36901814 3 29 theme model 435:439 arg1 suspensions 441:451 model suspensions 435:451 model suspensions 435:451 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 4 30 theme content 615:621 arg1 influence 584:592 The influence 580:592 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy 580:779 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 7 31 theme analysis/EDX 1281:1292 arg1 data 1294:1297 The surface morphology analysis/EDX data 1258:1297 The surface morphology analysis/EDX data 1258:1297 The surface morphology analysis/EDX data provided supplementary evidence regarding the separation process. 36901814 5 32 theme FeO 887:889 arg1 particles 891:899 the FeO particles 883:899 the FeO particles (around 95% and more) 883:921 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 5 33 theme characteristics 967:981 arg1 irrespective 924:935 irrespective 924:935 irrespective 924:935 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 4 34 theme initial 634:640 arg1 concentration 651:663 initial solution concentration 634:663 initial solution concentration 634:663 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 5 35 theme spectroscopy 805:816 arg1 measurements 818:829 UV-Vis spectroscopy measurements 798:829 UV-Vis spectroscopy measurements 798:829 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 3 36 theme carbamate 553:561 arg1 TMAP 573:576 TMAP 573:576 TMAP 573:576 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 36 theme carbamate 553:561 arg1 chloride 563:570 trimethylammonium propyl carbamate chloride 528:570 trimethylammonium propyl carbamate chloride (TMAP) 528:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 36 theme carbamate 553:561 arg1 groups 520:525 pendant quaternary ammonium salt groups 487:525 pendant quaternary ammonium salt groups 487:525 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 5 37 theme particles 1018:1026 arg1 clarification 992:1004 a lower clarification 984:1004 a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) 984:1078 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 1 38 theme Modified 108:115 arg1 polysaccharides 117:131 Modified polysaccharides 108:131 Modified polysaccharides 108:131 Modified polysaccharides have been increasingly used as flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc. 36901814 1 38 theme Modified 108:115 arg1 flocculants 164:174 flocculants 164:174 flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc 164:258 Modified polysaccharides have been increasingly used as flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc. 36901814 8 39 from efficiency 1380:1389 arg1 wastewater 1485:1494 simulated wastewater 1475:1494 simulated wastewater 1475:1494 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 4 40 theme dispersion 683:692 arg1 pH 694:695 dispersion pH 683:695 dispersion pH 683:695 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 3 41 theme particle 413:420 arg1 removal 422:428 TiO2 particle removal 408:428 TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP) 408:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 4 42 theme composition 701:711 arg1 influence 584:592 The influence 580:592 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy 580:779 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 3 43 with derivatives 470:480 arg1 chloride 563:570 trimethylammonium propyl carbamate chloride 528:570 trimethylammonium propyl carbamate chloride (TMAP) 528:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 43 with derivatives 470:480 arg1 groups 520:525 pendant quaternary ammonium salt groups 487:525 pendant quaternary ammonium salt groups 487:525 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 8 44 theme flocs 1429:1433 arg1 efficiency 1380:1389 A good removal efficiency 1365:1389 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater 1365:1494 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 8 44 theme flocs 1429:1433 arg1 % 1394:1394 90% 1392:1394 90% 1392:1394 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 4 45 theme solution 642:649 arg1 concentration 651:663 initial solution concentration 634:663 initial solution concentration 634:663 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 6 46 theme charge 1176:1181 arg1 patch 1183:1187 the charge patch 1172:1187 the charge patch 1172:1187 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 6 46 theme charge 1176:1181 arg1 mechanism 1201:1209 the main mechanism 1192:1209 the main mechanism which governs the metal oxide removal process 1192:1255 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 7 47 theme surface 1262:1268 arg1 data 1294:1297 The surface morphology analysis/EDX data 1258:1297 The surface morphology analysis/EDX data 1258:1297 The surface morphology analysis/EDX data provided supplementary evidence regarding the separation process. 36901814 8 48 from wastewater 1485:1494 arg1 efficiency 1380:1389 A good removal efficiency 1365:1389 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater 1365:1494 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 8 48 from wastewater 1485:1494 arg1 % 1394:1394 90% 1392:1394 90% 1392:1394 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 8 48 from wastewater 1485:1494 arg1 flocs 1429:1433 the pullulan derivatives/FeO flocs 1400:1433 the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater 1400:1494 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 5 49 theme UV-Vis 798:803 arg1 measurements 818:829 UV-Vis spectroscopy measurements 798:829 UV-Vis spectroscopy measurements 798:829 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 1 50 theme low 227:229 arg1 non-toxicity 213:224 their non-toxicity 207:224 their non-toxicity 207:224 Modified polysaccharides have been increasingly used as flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc. 36901814 1 50 theme low 227:229 arg1 price 231:235 low price 227:235 low price 227:235 Modified polysaccharides have been increasingly used as flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc. 36901814 8 51 theme pullulan 1404:1411 arg1 flocs 1429:1433 the pullulan derivatives/FeO flocs 1400:1433 the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater 1400:1494 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 5 52 theme removal 1040:1046 arg1 efficiency 1048:1057 removal efficiency 1040:1057 removal efficiency between 68% and 75% 1040:1077 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 8 53 theme good 1367:1370 arg1 efficiency 1380:1389 A good removal efficiency 1365:1389 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater 1365:1494 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 8 53 theme good 1367:1370 arg1 % 1394:1394 90% 1392:1394 90% 1392:1394 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 3 54 theme ammonium 506:513 arg1 chloride 563:570 trimethylammonium propyl carbamate chloride 528:570 trimethylammonium propyl carbamate chloride (TMAP) 528:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 54 theme ammonium 506:513 arg1 groups 520:525 pendant quaternary ammonium salt groups 487:525 pendant quaternary ammonium salt groups 487:525 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 55 theme TiO2 408:411 arg1 removal 422:428 TiO2 particle removal 408:428 TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP) 408:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 6 56 theme removal 1241:1247 arg1 process 1249:1255 the metal oxide removal process 1225:1255 the metal oxide removal process 1225:1255 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 8 57 theme derivatives/FeO 1413:1427 arg1 flocs 1429:1433 the pullulan derivatives/FeO flocs 1400:1433 the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater 1400:1494 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 5 58 theme lower 986:990 arg1 clarification 992:1004 a lower clarification 984:1004 a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) 984:1078 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 7 59 theme morphology 1270:1279 arg1 data 1294:1297 The surface morphology analysis/EDX data 1258:1297 The surface morphology analysis/EDX data 1258:1297 The surface morphology analysis/EDX data provided supplementary evidence regarding the separation process. 36901814 3 60 theme salt 515:518 arg1 chloride 563:570 trimethylammonium propyl carbamate chloride 528:570 trimethylammonium propyl carbamate chloride (TMAP) 528:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 60 theme salt 515:518 arg1 groups 520:525 pendant quaternary ammonium salt groups 487:525 pendant quaternary ammonium salt groups 487:525 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 6 61 theme oxide 1235:1239 arg1 process 1249:1255 the metal oxide removal process 1225:1255 the metal oxide removal process 1225:1255 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 6 62 theme size 1145:1148 arg1 measurements 1150:1161 Both the zeta potential and the particle aggregates size measurements 1093:1161 Both the zeta potential and the particle aggregates size measurements 1093:1161 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 4 63 theme separation 761:770 arg1 efficacy 772:779 the separation efficacy 757:779 the separation efficacy 757:779 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 7 64 theme separation 1345:1354 arg1 process 1356:1362 the separation process 1341:1362 the separation process 1341:1362 The surface morphology analysis/EDX data provided supplementary evidence regarding the separation process. 36901814 3 65 theme pendant 487:493 arg1 chloride 563:570 trimethylammonium propyl carbamate chloride 528:570 trimethylammonium propyl carbamate chloride (TMAP) 528:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 65 theme pendant 487:493 arg1 groups 520:525 pendant quaternary ammonium salt groups 487:525 pendant quaternary ammonium salt groups 487:525 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 2 66 used used 304:307 arg2 derivatives 283:293 the pullulan derivatives 270:293 the pullulan derivatives 270:293 However, the pullulan derivatives are less used in wastewater purification processes. 36901814 6 67 theme metal 1229:1233 arg1 process 1249:1255 the metal oxide removal process 1225:1255 the metal oxide removal process 1225:1255 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 0 68 from Wastewater 96:105 arg1 Oxides 74:79 Some Metal Oxides 63:79 Some Metal Oxides from Simulated Wastewater 63:105 Cationic Pullulan Derivatives Based Flocculants for Removal of Some Metal Oxides from Simulated Wastewater. 36901814 0 68 from Wastewater 96:105 arg1 Removal 52:58 Removal 52:58 Removal of Some Metal Oxides from Simulated Wastewater 52:105 Cationic Pullulan Derivatives Based Flocculants for Removal of Some Metal Oxides from Simulated Wastewater. 36901814 5 69 theme polymer 944:950 arg1 characteristics 967:981 the polymer and suspension characteristics 940:981 characteristics 967:981 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 2 70 theme purification 323:334 arg1 processes 336:344 wastewater purification processes 312:344 wastewater purification processes 312:344 However, the pullulan derivatives are less used in wastewater purification processes. 36901814 4 71 theme oxide 720:724 arg1 content 726:732 metal oxide content 714:732 metal oxide content 714:732 The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. 36901814 0 72 theme Metal 68:72 arg1 Oxides 74:79 Some Metal Oxides 63:79 Some Metal Oxides from Simulated Wastewater 63:105 Cationic Pullulan Derivatives Based Flocculants for Removal of Some Metal Oxides from Simulated Wastewater. 36901814 3 73 theme pullulan 461:468 arg1 derivatives 470:480 some pullulan derivatives 456:480 some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP) 456:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 6 74 theme particle 1125:1132 arg1 size 1145:1148 the particle aggregates size 1121:1148 the particle aggregates size 1121:1148 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 3 75 theme trimethylammonium 528:544 arg1 TMAP 573:576 TMAP 573:576 TMAP 573:576 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 75 theme trimethylammonium 528:544 arg1 chloride 563:570 trimethylammonium propyl carbamate chloride 528:570 trimethylammonium propyl carbamate chloride (TMAP) 528:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 75 theme trimethylammonium 528:544 arg1 groups 520:525 pendant quaternary ammonium salt groups 487:525 pendant quaternary ammonium salt groups 487:525 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 6 76 theme zeta 1102:1105 arg1 potential 1107:1115 the zeta potential 1098:1115 the zeta potential 1098:1115 Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. 36901814 5 77 dep particles 1018:1026 arg1 suspension 1028:1037 suspension 1028:1037 the TiO2 particles suspension (removal efficiency between 68% and 75%) 1009:1078 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 8 78 theme Bordeaux 1443:1450 arg1 particles 1460:1468 the Bordeaux mixture particles 1439:1468 the Bordeaux mixture particles 1439:1468 A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found. 36901814 5 79 theme suspension 956:965 arg1 characteristics 967:981 the polymer and suspension characteristics 940:981 characteristics 967:981 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36901814 3 80 from suspensions 441:451 arg1 FeO 400:402 FeO 400:402 FeO 400:402 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 80 from suspensions 441:451 arg1 removal 422:428 TiO2 particle removal 408:428 TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP) 408:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 81 theme propyl 546:551 arg1 TMAP 573:576 TMAP 573:576 TMAP 573:576 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 81 theme propyl 546:551 arg1 chloride 563:570 trimethylammonium propyl carbamate chloride 528:570 trimethylammonium propyl carbamate chloride (TMAP) 528:577 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 3 81 theme propyl 546:551 arg1 groups 520:525 pendant quaternary ammonium salt groups 487:525 pendant quaternary ammonium salt groups 487:525 Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAP). 36901814 5 82 dep suspension 1028:1037 arg1 efficiency 1048:1057 removal efficiency 1040:1057 removal efficiency between 68% and 75% 1040:1077 UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAP for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. 36481495 8 0 theme bacterial 1205:1213 arg1 abundance 1215:1223 the total bacterial abundance 1195:1223 the total bacterial abundance 1195:1223 In contrast, the basophilic Exiguobacterium accounted for >80% of the total bacterial abundance at pH 9. 36481495 7 1 theme acid-resistant 984:997 arg1 Elizabethkingia 999:1013 The acid-resistant Elizabethkingia 980:1013 The acid-resistant Elizabethkingia 980:1013 The acid-resistant Elizabethkingia and Bacillus were abundant at pH 5, while Chryseobacterium and Klebsiella had relatively high abundances at pH 7. 36481495 7 1 theme acid-resistant 984:997 arg1 abundant 1033:1040 abundant 1033:1040 abundant 1033:1040 The acid-resistant Elizabethkingia and Bacillus were abundant at pH 5, while Chryseobacterium and Klebsiella had relatively high abundances at pH 7. 36481495 5 2 theme EPS 830:832 arg1 concentration 834:846 bacterial EPS concentration 820:846 bacterial EPS concentration 820:846 In addition, the difference in bacterial EPS concentration was mainly associated with the polysaccharides. 36481495 1 3 theme column 226:231 arg1 experiments 233:243 three laboratory-scale column experiments 203:243 three laboratory-scale column experiments 203:243 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 0 4 theme aquifer 62:68 arg1 MAR 80:82 MAR 80:82 MAR 80:82 Influence of pH on bioclogging in porous media during managed aquifer recharge (MAR): Effectiveness and mechanism. 36481495 0 4 theme aquifer 62:68 arg1 recharge 70:77 managed aquifer recharge 54:77 managed aquifer recharge (MAR) 54:83 Influence of pH on bioclogging in porous media during managed aquifer recharge (MAR): Effectiveness and mechanism. 36481495 6 5 theme bacterial 933:941 arg1 composition 953:963 different bacterial community composition 923:963 different bacterial community composition 923:963 The variation in pH led to different bacterial community composition and diversity. 36481495 4 6 theme lowest 740:745 arg1 number 747:752 lowest number 740:752 lowest number of bacteria 740:764 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 1 7 from effect 134:139 arg1 process 162:168 bioclogging process 150:168 bioclogging process during managed aquifer recharge 150:200 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 7 8 contain had 1089:1091 arg1 Klebsiella 1078:1087 Klebsiella 1078:1087 Klebsiella 1078:1087 The acid-resistant Elizabethkingia and Bacillus were abundant at pH 5, while Chryseobacterium and Klebsiella had relatively high abundances at pH 7. 36481495 7 8 contain had 1089:1091 arg1 Chryseobacterium 1057:1072 Chryseobacterium 1057:1072 Chryseobacterium 1057:1072 The acid-resistant Elizabethkingia and Bacillus were abundant at pH 5, while Chryseobacterium and Klebsiella had relatively high abundances at pH 7. 36481495 7 8 contain had 1089:1091 arg2 abundances 1109:1118 relatively high abundances 1093:1118 relatively high abundances 1093:1118 The acid-resistant Elizabethkingia and Bacillus were abundant at pH 5, while Chryseobacterium and Klebsiella had relatively high abundances at pH 7. 36481495 6 9 theme different 923:931 arg1 composition 953:963 different bacterial community composition 923:963 different bacterial community composition 923:963 The variation in pH led to different bacterial community composition and diversity. 36481495 4 10 dep 7 633:633 arg1 process 660:666 the growth process 649:666 the growth process 649:666 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 4 10 dep 7 633:633 arg1 number 672:677 number 672:677 number of bacteria 672:689 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 1 11 theme polysaccharide 349:362 arg1 number 316:321 bacterial cell number 301:321 bacterial cell number 301:321 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 1 11 theme polysaccharide 349:362 arg1 concentrations 331:344 the concentrations 327:344 the concentrations of polysaccharide, protein and EPS 327:379 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 1 11 theme polysaccharide 349:362 arg1 conductivity 287:298 the relative hydraulic conductivity 264:298 the relative hydraulic conductivity 264:298 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 4 12 theme growth 722:727 arg1 period 729:734 The shortest growth period 709:734 pH. The shortest growth period 705:734 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 8 13 theme total 1199:1203 arg1 abundance 1215:1223 the total bacterial abundance 1195:1223 the total bacterial abundance 1195:1223 In contrast, the basophilic Exiguobacterium accounted for >80% of the total bacterial abundance at pH 9. 36481495 9 14 theme aquifer 1382:1388 arg1 recharge 1390:1397 field-based managed aquifer recharge 1362:1397 field-based managed aquifer recharge 1362:1397 This work is of great significance to explore bioclogging mechanism during MAR process, and provides insights and guidances for field-based managed aquifer recharge. 36481495 6 15 theme community 943:951 arg1 composition 953:963 different bacterial community composition 923:963 different bacterial community composition 923:963 The variation in pH led to different bacterial community composition and diversity. 36481495 4 16 theme shortest 713:720 arg1 period 729:734 The shortest growth period 709:734 pH. The shortest growth period 705:734 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 1 17 theme pH 144:145 arg1 effect 134:139 the effect 130:139 the effect of pH on bioclogging process during managed aquifer recharge 130:200 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 8 18 theme basophilic 1146:1155 arg1 Exiguobacterium 1157:1171 the basophilic Exiguobacterium 1142:1171 the basophilic Exiguobacterium 1142:1171 In contrast, the basophilic Exiguobacterium accounted for >80% of the total bacterial abundance at pH 9. 36481495 1 19 theme protein 365:371 arg1 number 316:321 bacterial cell number 301:321 bacterial cell number 301:321 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 1 19 theme protein 365:371 arg1 concentrations 331:344 the concentrations 327:344 the concentrations of polysaccharide, protein and EPS 327:379 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 1 19 theme protein 365:371 arg1 conductivity 287:298 the relative hydraulic conductivity 264:298 the relative hydraulic conductivity 264:298 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 9 20 theme great 1250:1254 arg1 significance 1256:1267 great significance 1250:1267 great significance 1250:1267 This work is of great significance to explore bioclogging mechanism during MAR process, and provides insights and guidances for field-based managed aquifer recharge. 36481495 4 21 theme bacteria 682:689 arg1 process 660:666 the growth process 649:666 the growth process 649:666 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 4 21 theme bacteria 682:689 arg1 number 672:677 number 672:677 number of bacteria 672:689 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 8 22 theme abundance 1215:1223 arg1 abundance 1215:1223 the total bacterial abundance 1195:1223 the total bacterial abundance 1195:1223 In contrast, the basophilic Exiguobacterium accounted for >80% of the total bacterial abundance at pH 9. 36481495 8 22 theme abundance 1215:1223 arg1 % 1190:1190 >80% 1187:1190 >80% of the total bacterial abundance at pH 9 1187:1231 In contrast, the basophilic Exiguobacterium accounted for >80% of the total bacterial abundance at pH 9. 36481495 9 23 theme bioclogging 1280:1290 arg1 mechanism 1292:1300 bioclogging mechanism 1280:1300 bioclogging mechanism during MAR process 1280:1319 This work is of great significance to explore bioclogging mechanism during MAR process, and provides insights and guidances for field-based managed aquifer recharge. 36481495 7 24 from pH 5 1045:1048 arg1 Elizabethkingia 999:1013 The acid-resistant Elizabethkingia 980:1013 The acid-resistant Elizabethkingia 980:1013 The acid-resistant Elizabethkingia and Bacillus were abundant at pH 5, while Chryseobacterium and Klebsiella had relatively high abundances at pH 7. 36481495 7 24 from pH 5 1045:1048 arg1 abundant 1033:1040 abundant 1033:1040 abundant 1033:1040 The acid-resistant Elizabethkingia and Bacillus were abundant at pH 5, while Chryseobacterium and Klebsiella had relatively high abundances at pH 7. 36481495 4 25 located observed 771:778 arg2 number 747:752 lowest number 740:752 lowest number of bacteria 740:764 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 4 25 located observed 771:778 arg1 pH 5 783:786 pH 5 783:786 pH 5 783:786 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 1 26 theme bioclogging 150:160 arg1 process 162:168 bioclogging process 150:168 bioclogging process during managed aquifer recharge 150:200 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 2 27 theme different 534:542 arg1 conditions 547:556 different pH conditions 534:556 different pH conditions 534:556 High-throughput sequencing was also used to determine the characteristics of bacterial community under different pH conditions. 36481495 4 28 theme bacteria 757:764 arg1 number 747:752 lowest number 740:752 lowest number of bacteria 740:764 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 0 29 theme pH 13:14 arg1 Influence 0:8 Influence 0:8 Influence of pH on bioclogging in porous media during managed aquifer recharge (MAR): Effectiveness and mechanism. 0:113 Influence of pH on bioclogging in porous media during managed aquifer recharge (MAR): Effectiveness and mechanism. 36481495 1 30 theme relative 268:275 arg1 conductivity 287:298 the relative hydraulic conductivity 264:298 the relative hydraulic conductivity 264:298 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 6 31 from variation 900:908 arg1 pH 913:914 pH 913:914 pH 913:914 The variation in pH led to different bacterial community composition and diversity. 36481495 3 32 theme pH 5 627:630 arg1 case 619:622 the case 615:622 the case of pH 5 615:630 The development of bioclogging was rather different for the case of pH 5. 36481495 1 33 theme hydraulic 277:285 arg1 conductivity 287:298 the relative hydraulic conductivity 264:298 the relative hydraulic conductivity 264:298 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 2 34 theme community 518:526 arg1 characteristics 489:503 the characteristics 485:503 the characteristics of bacterial community 485:526 High-throughput sequencing was also used to determine the characteristics of bacterial community under different pH conditions. 36481495 1 35 theme EPS 377:379 arg1 number 316:321 bacterial cell number 301:321 bacterial cell number 301:321 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 1 35 theme EPS 377:379 arg1 concentrations 331:344 the concentrations 327:344 the concentrations of polysaccharide, protein and EPS 327:379 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 1 35 theme EPS 377:379 arg1 conductivity 287:298 the relative hydraulic conductivity 264:298 the relative hydraulic conductivity 264:298 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 3 36 theme bioclogging 578:588 arg1 different 601:609 different 601:609 different 601:609 The development of bioclogging was rather different for the case of pH 5. 36481495 3 36 theme bioclogging 578:588 arg1 development 563:573 The development 559:573 The development of bioclogging 559:588 The development of bioclogging was rather different for the case of pH 5. 36481495 4 37 dep period 729:734 arg1 pH. 705:707 pH. The shortest growth period 705:734 pH. The shortest growth period 705:734 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 1 38 theme managed 177:183 arg1 recharge 193:200 managed aquifer recharge 177:200 managed aquifer recharge 177:200 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 2 39 theme High-throughput 431:445 arg1 sequencing 447:456 High-throughput sequencing 431:456 High-throughput sequencing 431:456 High-throughput sequencing was also used to determine the characteristics of bacterial community under different pH conditions. 36481495 2 40 theme bacterial 508:516 arg1 community 518:526 bacterial community 508:526 bacterial community 508:526 High-throughput sequencing was also used to determine the characteristics of bacterial community under different pH conditions. 36481495 9 41 theme managed 1374:1380 arg1 recharge 1390:1397 field-based managed aquifer recharge 1362:1397 field-based managed aquifer recharge 1362:1397 This work is of great significance to explore bioclogging mechanism during MAR process, and provides insights and guidances for field-based managed aquifer recharge. 36481495 1 42 theme aquifer 185:191 arg1 recharge 193:200 managed aquifer recharge 177:200 managed aquifer recharge 177:200 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 7 43 theme high 1104:1107 arg1 abundances 1109:1118 relatively high abundances 1093:1118 relatively high abundances 1093:1118 The acid-resistant Elizabethkingia and Bacillus were abundant at pH 5, while Chryseobacterium and Klebsiella had relatively high abundances at pH 7. 36481495 0 44 theme porous 34:39 arg1 media 41:45 porous media 34:45 porous media 34:45 Influence of pH on bioclogging in porous media during managed aquifer recharge (MAR): Effectiveness and mechanism. 36481495 1 45 theme bacterial 301:309 arg1 number 316:321 bacterial cell number 301:321 bacterial cell number 301:321 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 4 46 theme growth 653:658 arg1 process 660:666 the growth process 649:666 the growth process 649:666 7, and 9; i.e., the growth process and number of bacteria differed with pH. The shortest growth period and lowest number of bacteria were observed at pH 5. 36481495 1 47 theme cell 311:314 arg1 number 316:321 bacterial cell number 301:321 bacterial cell number 301:321 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 36481495 9 48 theme MAR 1309:1311 arg1 process 1313:1319 MAR process 1309:1319 MAR process 1309:1319 This work is of great significance to explore bioclogging mechanism during MAR process, and provides insights and guidances for field-based managed aquifer recharge. 36481495 2 49 theme pH 544:545 arg1 conditions 547:556 different pH conditions 534:556 different pH conditions 534:556 High-throughput sequencing was also used to determine the characteristics of bacterial community under different pH conditions. 36481495 2 50 used used 467:470 arg2 sequencing 447:456 High-throughput sequencing 431:456 High-throughput sequencing 431:456 High-throughput sequencing was also used to determine the characteristics of bacterial community under different pH conditions. 36481495 0 51 theme managed 54:60 arg1 MAR 80:82 MAR 80:82 MAR 80:82 Influence of pH on bioclogging in porous media during managed aquifer recharge (MAR): Effectiveness and mechanism. 36481495 0 51 theme managed 54:60 arg1 recharge 70:77 managed aquifer recharge 54:77 managed aquifer recharge (MAR) 54:83 Influence of pH on bioclogging in porous media during managed aquifer recharge (MAR): Effectiveness and mechanism. 36481495 5 52 from difference 806:815 arg1 concentration 834:846 bacterial EPS concentration 820:846 bacterial EPS concentration 820:846 In addition, the difference in bacterial EPS concentration was mainly associated with the polysaccharides. 36481495 0 53 dep Influence 0:8 arg1 mechanism 104:112 mechanism 104:112 mechanism 104:112 Influence of pH on bioclogging in porous media during managed aquifer recharge (MAR): Effectiveness and mechanism. 36481495 0 53 dep Influence 0:8 arg1 Effectiveness 86:98 Effectiveness 86:98 Effectiveness 86:98 Influence of pH on bioclogging in porous media during managed aquifer recharge (MAR): Effectiveness and mechanism. 36481495 8 54 from pH 9 1228:1231 arg1 abundance 1215:1223 the total bacterial abundance 1195:1223 the total bacterial abundance 1195:1223 In contrast, the basophilic Exiguobacterium accounted for >80% of the total bacterial abundance at pH 9. 36481495 8 54 from pH 9 1228:1231 arg1 % 1190:1190 >80% 1187:1190 >80% of the total bacterial abundance at pH 9 1187:1231 In contrast, the basophilic Exiguobacterium accounted for >80% of the total bacterial abundance at pH 9. 36481495 5 55 theme bacterial 820:828 arg1 concentration 834:846 bacterial EPS concentration 820:846 bacterial EPS concentration 820:846 In addition, the difference in bacterial EPS concentration was mainly associated with the polysaccharides. 36481495 9 56 theme field-based 1362:1372 arg1 recharge 1390:1397 field-based managed aquifer recharge 1362:1397 field-based managed aquifer recharge 1362:1397 This work is of great significance to explore bioclogging mechanism during MAR process, and provides insights and guidances for field-based managed aquifer recharge. 36481495 1 57 theme laboratory-scale 209:224 arg1 experiments 233:243 three laboratory-scale column experiments 203:243 three laboratory-scale column experiments 203:243 To investigate the effect of pH on bioclogging process during managed aquifer recharge, three laboratory-scale column experiments were conducted and the relative hydraulic conductivity, bacterial cell number and the concentrations of polysaccharide, protein and EPS were measured under pH 5, 7, and 9, respectively. 35318351 3 0 theme microbiome 682:691 arg1 contribution 693:704 the lower gut microbiome contribution 668:704 the lower gut microbiome contribution to these traits 668:720 Although the contribution of the rumen microbiome to production efficiency in dairy cows has been widely researched over the years, variations throughout the lactation and the lower gut microbiome contribution to these traits remain poorly characterized. 35318351 4 1 theme efficiency 876:885 arg1 traits 887:892 production efficiency traits 865:892 production efficiency traits in Holstein cows 865:909 Therefore, we investigated throughout lactation the relationship between the rumen and lower gut microbiomes with production efficiency traits in Holstein cows. 35318351 1 2 theme dietary 153:159 arg1 nutrients 161:169 dietary nutrients 153:169 dietary nutrients 153:169 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract is an essential mechanism utilized to meet daily energy requirements. 35318351 4 3 with microbiomes 848:858 arg1 traits 887:892 production efficiency traits 865:892 production efficiency traits in Holstein cows 865:909 Therefore, we investigated throughout lactation the relationship between the rumen and lower gut microbiomes with production efficiency traits in Holstein cows. 35318351 2 4 theme gluconeogenic 451:463 arg1 precursors 465:474 gluconeogenic precursors 451:474 gluconeogenic precursors 451:474 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 4 5 theme production 865:874 arg1 traits 887:892 production efficiency traits 865:892 production efficiency traits in Holstein cows 865:909 Therefore, we investigated throughout lactation the relationship between the rumen and lower gut microbiomes with production efficiency traits in Holstein cows. 35318351 1 6 theme nutrients 161:169 arg1 mechanism 229:237 an essential mechanism 216:237 an essential mechanism utilized to meet daily energy requirements 216:280 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract is an essential mechanism utilized to meet daily energy requirements. 35318351 1 6 theme nutrients 161:169 arg1 Fermentation 137:148 Fermentation 137:148 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract 137:211 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract is an essential mechanism utilized to meet daily energy requirements. 35318351 7 7 theme gut 1197:1199 arg1 microbiome 1201:1210 the lower gut microbiome 1187:1210 the lower gut microbiome 1187:1210 In contrast, the lower gut microbiome was less dependent on feed intake and associated with a potentially enhanced ability to digest dietary nutrients. 35318351 7 7 theme gut 1197:1199 arg1 dependent 1221:1229 dependent 1221:1229 dependent 1221:1229 In contrast, the lower gut microbiome was less dependent on feed intake and associated with a potentially enhanced ability to digest dietary nutrients. 35318351 3 8 theme lower 672:676 arg1 contribution 693:704 the lower gut microbiome contribution 668:704 the lower gut microbiome contribution to these traits 668:720 Although the contribution of the rumen microbiome to production efficiency in dairy cows has been widely researched over the years, variations throughout the lactation and the lower gut microbiome contribution to these traits remain poorly characterized. 35318351 5 9 theme temporal 965:972 arg1 stability 974:982 temporal stability 965:982 temporal stability 965:982 We found that the microbiome from both locations has temporal stability throughout lactation, yet factors such as feed intake levels played a significant role in shaping microbiome diversity. 35318351 9 10 theme microbiomes 1565:1575 arg1 relationship 1525:1536 the temporal relationship 1512:1536 the temporal relationship of the rumen and lower gut microbiomes 1512:1575 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 6 11 theme feed 1161:1164 arg1 intake 1166:1171 feed intake 1161:1171 feed intake 1161:1171 The composition of the rumen microbiome was dependent on feed intake. 35318351 8 12 theme milk 1337:1340 arg1 production 1342:1351 milk production 1337:1351 milk production traits 1337:1358 Therefore, milk production traits may be more correlated with microorganisms present in the lower gut than previously expected. 35318351 9 13 theme livestock 1681:1689 arg1 production 1691:1700 more sustainable livestock production 1664:1700 more sustainable livestock production 1664:1700 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 3 14 theme rumen 529:533 arg1 microbiome 535:544 the rumen microbiome 525:544 the rumen microbiome 525:544 Although the contribution of the rumen microbiome to production efficiency in dairy cows has been widely researched over the years, variations throughout the lactation and the lower gut microbiome contribution to these traits remain poorly characterized. 35318351 1 15 theme daily 256:260 arg1 requirements 269:280 daily energy requirements 256:280 daily energy requirements 256:280 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract is an essential mechanism utilized to meet daily energy requirements. 35318351 4 16 theme gut 844:846 arg1 microbiomes 848:858 lower gut microbiomes 838:858 lower gut microbiomes 838:858 Therefore, we investigated throughout lactation the relationship between the rumen and lower gut microbiomes with production efficiency traits in Holstein cows. 35318351 2 17 theme polysaccharides 397:411 arg1 breakdown 365:373 the breakdown 361:373 the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis 361:493 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 9 18 theme lower 1555:1559 arg1 microbiomes 1565:1575 the rumen and lower gut microbiomes 1541:1575 the rumen and lower gut microbiomes 1541:1575 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 7 19 theme lower 1191:1195 arg1 microbiome 1201:1210 the lower gut microbiome 1187:1210 the lower gut microbiome 1187:1210 In contrast, the lower gut microbiome was less dependent on feed intake and associated with a potentially enhanced ability to digest dietary nutrients. 35318351 7 19 theme lower 1191:1195 arg1 dependent 1221:1229 dependent 1221:1229 dependent 1221:1229 In contrast, the lower gut microbiome was less dependent on feed intake and associated with a potentially enhanced ability to digest dietary nutrients. 35318351 7 20 from contrast 1177:1184 arg1 microbiome 1201:1210 the lower gut microbiome 1187:1210 the lower gut microbiome 1187:1210 In contrast, the lower gut microbiome was less dependent on feed intake and associated with a potentially enhanced ability to digest dietary nutrients. 35318351 7 20 from contrast 1177:1184 arg1 dependent 1221:1229 dependent 1221:1229 dependent 1221:1229 In contrast, the lower gut microbiome was less dependent on feed intake and associated with a potentially enhanced ability to digest dietary nutrients. 35318351 4 21 theme lower 838:842 arg1 microbiomes 848:858 lower gut microbiomes 838:858 lower gut microbiomes 838:858 Therefore, we investigated throughout lactation the relationship between the rumen and lower gut microbiomes with production efficiency traits in Holstein cows. 35318351 7 22 theme dietary 1307:1313 arg1 nutrients 1315:1323 dietary nutrients 1307:1323 dietary nutrients 1307:1323 In contrast, the lower gut microbiome was less dependent on feed intake and associated with a potentially enhanced ability to digest dietary nutrients. 35318351 2 23 theme AAs 429:431 arg1 breakdown 365:373 the breakdown 361:373 the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis 361:493 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 8 24 from present 1403:1409 arg1 gut 1424:1426 the lower gut 1414:1426 the lower gut than previously expected 1414:1451 Therefore, milk production traits may be more correlated with microorganisms present in the lower gut than previously expected. 35318351 8 25 attach present 1403:1409 arg2 microorganisms 1388:1401 microorganisms 1388:1401 microorganisms present in the lower gut than previously expected 1388:1451 Therefore, milk production traits may be more correlated with microorganisms present in the lower gut than previously expected. 35318351 8 25 attach present 1403:1409 arg1 gut 1424:1426 the lower gut 1414:1426 the lower gut than previously expected 1414:1451 Therefore, milk production traits may be more correlated with microorganisms present in the lower gut than previously expected. 35318351 8 26 theme lower 1418:1422 arg1 gut 1424:1426 the lower gut 1414:1426 the lower gut than previously expected 1414:1451 Therefore, milk production traits may be more correlated with microorganisms present in the lower gut than previously expected. 35318351 3 27 theme production 549:558 arg1 efficiency 560:569 production efficiency 549:569 production efficiency in dairy cows 549:583 Although the contribution of the rumen microbiome to production efficiency in dairy cows has been widely researched over the years, variations throughout the lactation and the lower gut microbiome contribution to these traits remain poorly characterized. 35318351 0 28 theme Rumen 0:4 arg1 relationship 32:43 Rumen and lower gut microbiomes relationship 0:43 Rumen and lower gut microbiomes relationship with feed efficiency and production 0:79 Rumen and lower gut microbiomes relationship with feed efficiency and production traits throughout the lactation of Holstein dairy cows. 35318351 1 29 theme energy 262:267 arg1 requirements 269:280 daily energy requirements 256:280 daily energy requirements 256:280 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract is an essential mechanism utilized to meet daily energy requirements. 35318351 9 30 theme microbiome 1619:1628 arg1 overview 1599:1606 a broader overview 1589:1606 a broader overview of the gut microbiome 1589:1628 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 9 30 theme microbiome 1619:1628 arg1 production 1634:1643 production 1634:1643 production 1634:1643 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 9 31 theme rumen 1545:1549 arg1 microbiomes 1565:1575 the rumen and lower gut microbiomes 1541:1575 the rumen and lower gut microbiomes 1541:1575 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 2 32 theme dairy 307:311 arg1 cows 313:316 lactating dairy cows 297:316 lactating dairy cows 297:316 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 5 33 contain has 961:963 arg2 stability 974:982 temporal stability 965:982 temporal stability 965:982 We found that the microbiome from both locations has temporal stability throughout lactation, yet factors such as feed intake levels played a significant role in shaping microbiome diversity. 35318351 5 33 contain has 961:963 arg1 microbiome 930:939 the microbiome 926:939 the microbiome from both locations 926:959 We found that the microbiome from both locations has temporal stability throughout lactation, yet factors such as feed intake levels played a significant role in shaping microbiome diversity. 35318351 1 34 theme gastrointestinal 185:200 arg1 tract 207:211 ruminants' gastrointestinal (GI) tract 174:211 ruminants' gastrointestinal (GI) tract 174:211 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract is an essential mechanism utilized to meet daily energy requirements. 35318351 0 35 theme gut 16:18 arg1 microbiomes 20:30 lower gut microbiomes 10:30 lower gut microbiomes 10:30 Rumen and lower gut microbiomes relationship with feed efficiency and production traits throughout the lactation of Holstein dairy cows. 35318351 0 36 theme dairy 125:129 arg1 cows 131:134 Holstein dairy cows 116:134 Holstein dairy cows 116:134 Rumen and lower gut microbiomes relationship with feed efficiency and production traits throughout the lactation of Holstein dairy cows. 35318351 2 37 theme lactating 297:305 arg1 cows 313:316 lactating dairy cows 297:316 lactating dairy cows 297:316 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 9 38 theme broader 1591:1597 arg1 overview 1599:1606 a broader overview 1589:1606 a broader overview of the gut microbiome 1589:1628 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 2 39 theme supply 417:422 arg1 AAs 429:431 supply most AAs 417:431 supply most AAs 417:431 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 4 40 from traits 887:892 arg1 cows 906:909 Holstein cows 897:909 Holstein cows 897:909 Therefore, we investigated throughout lactation the relationship between the rumen and lower gut microbiomes with production efficiency traits in Holstein cows. 35318351 0 41 theme Holstein 116:123 arg1 cows 131:134 Holstein dairy cows 116:134 Holstein dairy cows 116:134 Rumen and lower gut microbiomes relationship with feed efficiency and production traits throughout the lactation of Holstein dairy cows. 35318351 7 42 theme feed 1234:1237 arg1 intake 1239:1244 feed intake 1234:1244 feed intake 1234:1244 In contrast, the lower gut microbiome was less dependent on feed intake and associated with a potentially enhanced ability to digest dietary nutrients. 35318351 8 43 from gut 1424:1426 arg1 present 1403:1409 present 1403:1409 present 1403:1409 Therefore, milk production traits may be more correlated with microorganisms present in the lower gut than previously expected. 35318351 1 44 theme GI 203:204 arg1 tract 207:211 ruminants' gastrointestinal (GI) tract 174:211 ruminants' gastrointestinal (GI) tract 174:211 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract is an essential mechanism utilized to meet daily energy requirements. 35318351 6 45 theme microbiome 1133:1142 arg1 composition 1108:1118 The composition 1104:1118 The composition of the rumen microbiome 1104:1142 The composition of the rumen microbiome was dependent on feed intake. 35318351 6 45 theme microbiome 1133:1142 arg1 dependent 1148:1156 dependent 1148:1156 dependent 1148:1156 The composition of the rumen microbiome was dependent on feed intake. 35318351 5 46 theme shaping 1074:1080 arg1 diversity 1093:1101 shaping microbiome diversity 1074:1101 shaping microbiome diversity 1074:1101 We found that the microbiome from both locations has temporal stability throughout lactation, yet factors such as feed intake levels played a significant role in shaping microbiome diversity. 35318351 8 47 theme present 1403:1409 arg1 microorganisms 1388:1401 microorganisms 1388:1401 microorganisms present in the lower gut than previously expected 1388:1451 Therefore, milk production traits may be more correlated with microorganisms present in the lower gut than previously expected. 35318351 9 48 theme current 1458:1464 arg1 findings 1474:1481 The current study's findings 1454:1481 The current study's findings 1454:1481 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 2 49 theme plant 391:395 arg1 polysaccharides 397:411 indigestible plant polysaccharides 378:411 indigestible plant polysaccharides 378:411 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 0 50 theme microbiomes 20:30 arg1 relationship 32:43 Rumen and lower gut microbiomes relationship 0:43 Rumen and lower gut microbiomes relationship with feed efficiency and production 0:79 Rumen and lower gut microbiomes relationship with feed efficiency and production traits throughout the lactation of Holstein dairy cows. 35318351 0 51 theme cows 131:134 arg1 lactation 103:111 the lactation 99:111 the lactation of Holstein dairy cows 99:134 Rumen and lower gut microbiomes relationship with feed efficiency and production traits throughout the lactation of Holstein dairy cows. 35318351 5 52 theme microbiome 1082:1091 arg1 diversity 1093:1101 shaping microbiome diversity 1074:1101 shaping microbiome diversity 1074:1101 We found that the microbiome from both locations has temporal stability throughout lactation, yet factors such as feed intake levels played a significant role in shaping microbiome diversity. 35318351 2 53 theme most 424:427 arg1 AAs 429:431 supply most AAs 417:431 supply most AAs 417:431 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 2 54 theme indigestible 378:389 arg1 polysaccharides 397:411 indigestible plant polysaccharides 378:411 indigestible plant polysaccharides 378:411 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 0 55 theme feed 50:53 arg1 efficiency 55:64 feed efficiency 50:64 feed efficiency 50:64 Rumen and lower gut microbiomes relationship with feed efficiency and production traits throughout the lactation of Holstein dairy cows. 35318351 9 56 dep overview 1599:1606 arg1 efficiency 1645:1654 efficiency 1645:1654 efficiency 1645:1654 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 5 57 theme intake 1031:1036 arg1 levels 1038:1043 feed intake levels 1026:1043 feed intake levels 1026:1043 We found that the microbiome from both locations has temporal stability throughout lactation, yet factors such as feed intake levels played a significant role in shaping microbiome diversity. 35318351 2 58 theme fatty 434:438 arg1 acids 440:444 fatty acids 434:444 fatty acids 434:444 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 8 59 dep gut 1424:1426 arg1 expected 1444:1451 expected 1444:1451 expected 1444:1451 Therefore, milk production traits may be more correlated with microorganisms present in the lower gut than previously expected. 35318351 4 60 theme Holstein 897:904 arg1 cows 906:909 Holstein cows 897:909 Holstein cows 897:909 Therefore, we investigated throughout lactation the relationship between the rumen and lower gut microbiomes with production efficiency traits in Holstein cows. 35318351 4 61 dep rumen 828:832 arg1 the 824:826 the 824:826 the 824:826 Therefore, we investigated throughout lactation the relationship between the rumen and lower gut microbiomes with production efficiency traits in Holstein cows. 35318351 3 62 theme dairy 574:578 arg1 cows 580:583 dairy cows 574:583 dairy cows 574:583 Although the contribution of the rumen microbiome to production efficiency in dairy cows has been widely researched over the years, variations throughout the lactation and the lower gut microbiome contribution to these traits remain poorly characterized. 35318351 9 63 theme sustainable 1669:1679 arg1 production 1691:1700 more sustainable livestock production 1664:1700 more sustainable livestock production 1664:1700 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 2 64 theme GI 323:324 arg1 microbiome 326:335 the GI microbiome 319:335 the GI microbiome 319:335 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 5 65 from locations 951:959 arg1 microbiome 930:939 the microbiome 926:939 the microbiome from both locations 926:959 We found that the microbiome from both locations has temporal stability throughout lactation, yet factors such as feed intake levels played a significant role in shaping microbiome diversity. 35318351 9 66 theme gut 1615:1617 arg1 microbiome 1619:1628 the gut microbiome 1611:1628 the gut microbiome 1611:1628 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 7 67 from dependent 1221:1229 arg1 contrast 1177:1184 contrast 1177:1184 contrast 1177:1184 In contrast, the lower gut microbiome was less dependent on feed intake and associated with a potentially enhanced ability to digest dietary nutrients. 35318351 5 68 theme feed 1026:1029 arg1 levels 1038:1043 feed intake levels 1026:1043 feed intake levels 1026:1043 We found that the microbiome from both locations has temporal stability throughout lactation, yet factors such as feed intake levels played a significant role in shaping microbiome diversity. 35318351 6 69 theme rumen 1127:1131 arg1 microbiome 1133:1142 the rumen microbiome 1123:1142 the rumen microbiome 1123:1142 The composition of the rumen microbiome was dependent on feed intake. 35318351 3 70 theme microbiome 535:544 arg1 contribution 509:520 the contribution 505:520 the contribution of the rumen microbiome to production efficiency in dairy cows 505:583 Although the contribution of the rumen microbiome to production efficiency in dairy cows has been widely researched over the years, variations throughout the lactation and the lower gut microbiome contribution to these traits remain poorly characterized. 35318351 9 71 theme gut 1561:1563 arg1 microbiomes 1565:1575 the rumen and lower gut microbiomes 1541:1575 the rumen and lower gut microbiomes 1541:1575 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 5 72 theme significant 1054:1064 arg1 role 1066:1069 a significant role 1052:1069 a significant role 1052:1069 We found that the microbiome from both locations has temporal stability throughout lactation, yet factors such as feed intake levels played a significant role in shaping microbiome diversity. 35318351 8 73 theme production 1342:1351 arg1 traits 1353:1358 milk production traits 1337:1358 milk production traits 1337:1358 Therefore, milk production traits may be more correlated with microorganisms present in the lower gut than previously expected. 35318351 9 74 theme relationship 1525:1536 arg1 understanding 1495:1507 our understanding 1491:1507 our understanding of the temporal relationship of the rumen and lower gut microbiomes 1491:1575 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 4 75 with rumen 828:832 arg1 traits 887:892 production efficiency traits 865:892 production efficiency traits in Holstein cows 865:909 Therefore, we investigated throughout lactation the relationship between the rumen and lower gut microbiomes with production efficiency traits in Holstein cows. 35318351 2 76 theme milk 480:483 arg1 synthesis 485:493 milk synthesis 480:493 milk synthesis 480:493 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 9 77 theme temporal 1516:1523 arg1 relationship 1525:1536 the temporal relationship 1512:1536 the temporal relationship of the rumen and lower gut microbiomes 1512:1575 The current study's findings advance our understanding of the temporal relationship of the rumen and lower gut microbiomes by enabling a broader overview of the gut microbiome and production efficiency towards more sustainable livestock production. 35318351 3 78 from efficiency 560:569 arg1 cows 580:583 dairy cows 574:583 dairy cows 574:583 Although the contribution of the rumen microbiome to production efficiency in dairy cows has been widely researched over the years, variations throughout the lactation and the lower gut microbiome contribution to these traits remain poorly characterized. 35318351 1 79 theme essential 219:227 arg1 mechanism 229:237 an essential mechanism 216:237 an essential mechanism utilized to meet daily energy requirements 216:280 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract is an essential mechanism utilized to meet daily energy requirements. 35318351 1 79 theme essential 219:227 arg1 Fermentation 137:148 Fermentation 137:148 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract 137:211 Fermentation of dietary nutrients in ruminants' gastrointestinal (GI) tract is an essential mechanism utilized to meet daily energy requirements. 35318351 3 80 theme gut 678:680 arg1 contribution 693:704 the lower gut microbiome contribution 668:704 the lower gut microbiome contribution to these traits 668:720 Although the contribution of the rumen microbiome to production efficiency in dairy cows has been widely researched over the years, variations throughout the lactation and the lower gut microbiome contribution to these traits remain poorly characterized. 35318351 0 81 theme lower 10:14 arg1 microbiomes 20:30 lower gut microbiomes 10:30 lower gut microbiomes 10:30 Rumen and lower gut microbiomes relationship with feed efficiency and production traits throughout the lactation of Holstein dairy cows. 35318351 0 82 with relationship 32:43 arg1 production 70:79 production 70:79 production 70:79 Rumen and lower gut microbiomes relationship with feed efficiency and production traits throughout the lactation of Holstein dairy cows. 35318351 0 82 with relationship 32:43 arg1 efficiency 55:64 feed efficiency 50:64 feed efficiency 50:64 Rumen and lower gut microbiomes relationship with feed efficiency and production traits throughout the lactation of Holstein dairy cows. 35318351 2 83 theme pivotal 345:351 arg1 role 353:356 a pivotal role 343:356 a pivotal role 343:356 Especially in lactating dairy cows, the GI microbiome plays a pivotal role in the breakdown of indigestible plant polysaccharides and supply most AAs, fatty acids, and gluconeogenic precursors for milk synthesis. 35318351 7 84 theme enhanced 1280:1287 arg1 ability 1289:1295 a potentially enhanced ability 1266:1295 a potentially enhanced ability to digest dietary nutrients 1266:1323 In contrast, the lower gut microbiome was less dependent on feed intake and associated with a potentially enhanced ability to digest dietary nutrients. 36144450 0 0 theme Potato 86:91 arg1 By-Products 100:110 Potato Starch By-Products 86:110 Potato Starch By-Products 86:110 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 4 1 with polysaccharides 840:854 arg1 distributions 897:909 two molecular weight distributions 876:909 two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity 876:976 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 2 2 theme niger 348:352 arg1 effect 335:340 the effect 331:340 the effect of A. niger applied towards the production of by-products recycling 331:408 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 4 3 dep proteins 813:820 arg1 w/w 831:833 w/w 831:833 w/w 831:833 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 4 3 dep proteins 813:820 arg1 % 828:828 45.55% 823:828 45.55% 823:828 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 3 4 theme cellulose 670:678 arg1 % 727:727 58.85% 722:727 58.85% 722:727 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 4 theme cellulose 670:678 arg1 rates 661:665 the conversion rates 646:665 the conversion rates of cellulose, hemicellulose, pectin, and proteins 646:715 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 4 theme cellulose 670:678 arg1 rate 636:639 the chemical oxygen demand (COD) removal rate 595:639 the chemical oxygen demand (COD) removal rate 595:639 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 4 5 dep polysaccharides 840:854 arg1 w/w 865:867 w/w 865:867 w/w 865:867 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 4 5 dep polysaccharides 840:854 arg1 % 862:862 28.07% 857:862 28.07% 857:862 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 1 6 theme practical 173:181 arg1 recovery 183:190 a practical recovery 171:190 a practical recovery for potato starch by-products 171:220 This study developed a practical recovery for potato starch by-products by A. niger and applied it on a plant scale to completely solve the pollution problems. 36144450 1 7 theme plant 254:258 arg1 scale 260:264 a plant scale 252:264 a plant scale 252:264 This study developed a practical recovery for potato starch by-products by A. niger and applied it on a plant scale to completely solve the pollution problems. 36144450 0 8 theme By-Products 100:110 arg1 Recovery 74:81 Industrial Recovery 63:81 Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics 63:147 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 0 9 from Application 0:10 arg1 Biotechnology 46:58 Practical Biotechnology 36:58 Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics 36:147 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 0 10 theme Starch 93:98 arg1 By-Products 100:110 Potato Starch By-Products 86:110 Potato Starch By-Products 86:110 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 3 11 theme proteins 708:715 arg1 % 727:727 58.85% 722:727 58.85% 722:727 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 11 theme proteins 708:715 arg1 rates 661:665 the conversion rates 646:665 the conversion rates of cellulose, hemicellulose, pectin, and proteins 646:715 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 11 theme proteins 708:715 arg1 rate 636:639 the chemical oxygen demand (COD) removal rate 595:639 the chemical oxygen demand (COD) removal rate 595:639 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 7 12 theme resource 1194:1201 arg1 waste 1203:1207 resource waste 1194:1207 resource waste 1194:1207 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 2 13 theme by-products 388:398 arg1 recycling 400:408 by-products recycling 388:408 by-products recycling 388:408 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 4 14 theme molecular 880:888 arg1 distributions 897:909 two molecular weight distributions 876:909 two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity 876:976 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 3 15 theme pectin 696:701 arg1 % 727:727 58.85% 722:727 58.85% 722:727 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 15 theme pectin 696:701 arg1 rates 661:665 the conversion rates 646:665 the conversion rates of cellulose, hemicellulose, pectin, and proteins 646:715 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 15 theme pectin 696:701 arg1 rate 636:639 the chemical oxygen demand (COD) removal rate 595:639 the chemical oxygen demand (COD) removal rate 595:639 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 2 16 dep composition 426:436 arg1 the 422:424 the 422:424 the 422:424 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 6 17 theme by-products 1124:1134 arg1 conversion 1136:1145 by-products conversion 1124:1145 by-products conversion 1124:1145 Flocculation was related to by-products conversion. 36144450 1 18 theme potato 196:201 arg1 by-products 210:220 potato starch by-products 196:220 potato starch by-products 196:220 This study developed a practical recovery for potato starch by-products by A. niger and applied it on a plant scale to completely solve the pollution problems. 36144450 4 19 theme weight 890:895 arg1 distributions 897:909 two molecular weight distributions 876:909 two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity 876:976 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 4 20 theme sensitivity 966:976 arg1 distributions 897:909 two molecular weight distributions 876:909 two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity 876:976 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 1 21 theme starch 203:208 arg1 by-products 210:220 potato starch by-products 196:220 potato starch by-products 196:220 This study developed a practical recovery for potato starch by-products by A. niger and applied it on a plant scale to completely solve the pollution problems. 36144450 0 22 theme niger 27:31 arg1 Application 0:10 Application 0:10 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 0:148 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 0 23 theme Characteristics 133:147 arg1 Recovery 74:81 Industrial Recovery 63:81 Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics 63:147 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 7 24 theme starch 1280:1285 arg1 by-products 1287:1297 converting potato starch by-products 1262:1297 converting potato starch by-products via A. niger 1262:1310 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 4 25 theme temperature 954:964 arg1 sensitivity 966:976 temperature sensitivity 954:976 temperature sensitivity 954:976 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 0 26 theme Aspergillus 15:25 arg1 niger 27:31 Aspergillus niger 15:31 Aspergillus niger 15:31 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 5 27 theme sweeping 1052:1059 arg1 effects 1061:1067 sweeping effects 1052:1067 sweeping effects 1052:1067 Flocculation was mainly through bridging and ionic bonding, furthermore, sweeping effects may occur during sediment. 36144450 0 28 theme Flocculation 120:131 arg1 Characteristics 133:147 Its Flocculation Characteristics 116:147 Its Flocculation Characteristics 116:147 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 4 29 with proteins 813:820 arg1 distributions 897:909 two molecular weight distributions 876:909 two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity 876:976 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 0 30 theme Practical 36:44 arg1 Biotechnology 46:58 Practical Biotechnology 36:58 Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics 36:147 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 1 31 theme pollution 290:298 arg1 problems 300:307 the pollution problems 286:307 the pollution problems 286:307 This study developed a practical recovery for potato starch by-products by A. niger and applied it on a plant scale to completely solve the pollution problems. 36144450 7 32 theme pollution 1171:1179 arg1 problems 1181:1188 severe pollution problems 1164:1188 severe pollution problems 1164:1188 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 3 33 theme chemical 599:606 arg1 % 727:727 58.85% 722:727 58.85% 722:727 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 33 theme chemical 599:606 arg1 rate 636:639 the chemical oxygen demand (COD) removal rate 595:639 the chemical oxygen demand (COD) removal rate 595:639 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 4 34 theme × 921:921 arg1 Da 927:928 7.3792 × 106 Da 914:928 7.3792 × 106 Da 914:928 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 7 35 theme severe 1164:1169 arg1 problems 1181:1188 severe pollution problems 1164:1188 severe pollution problems 1164:1188 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 2 36 theme flocculation 525:536 arg1 mechanism 538:546 a possible flocculation mechanism 514:546 a possible flocculation mechanism for by-product conversion 514:572 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 3 37 theme removal 628:634 arg1 % 727:727 58.85% 722:727 58.85% 722:727 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 37 theme removal 628:634 arg1 rate 636:639 the chemical oxygen demand (COD) removal rate 595:639 the chemical oxygen demand (COD) removal rate 595:639 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 38 theme oxygen 608:613 arg1 % 727:727 58.85% 722:727 58.85% 722:727 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 38 theme oxygen 608:613 arg1 rate 636:639 the chemical oxygen demand (COD) removal rate 595:639 the chemical oxygen demand (COD) removal rate 595:639 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 2 39 theme recycling 400:408 arg1 production 374:383 the production 370:383 the production of by-products recycling 370:408 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 2 40 theme substances 474:483 arg1 characteristics 442:456 characteristics 442:456 characteristics 442:456 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 2 40 theme substances 474:483 arg1 composition 426:436 composition 426:436 composition 426:436 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 2 41 theme possible 516:523 arg1 mechanism 538:546 a possible flocculation mechanism 514:546 a possible flocculation mechanism for by-product conversion 514:572 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 7 42 theme technologies 1248:1259 arg1 problems 1181:1188 severe pollution problems 1164:1188 severe pollution problems 1164:1188 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 7 42 theme technologies 1248:1259 arg1 waste 1203:1207 resource waste 1194:1207 resource waste 1194:1207 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 7 42 theme technologies 1248:1259 arg1 deficiencies 1214:1225 deficiencies 1214:1225 deficiencies of existing recovery technologies 1214:1259 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 7 43 theme significant 1339:1349 arg1 consideration 1351:1363 significant consideration 1339:1363 significant consideration 1339:1363 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 2 44 theme flocculating 461:472 arg1 substances 474:483 flocculating substances 461:483 flocculating substances (FS) 461:488 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 2 44 theme flocculating 461:472 arg1 FS 486:487 FS 486:487 FS 486:487 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 2 45 theme by-product 552:561 arg1 conversion 563:572 by-product conversion 552:572 by-product conversion 552:572 Soughing to evaluate the effect of A. niger applied towards the production of by-products recycling and analyze the composition and characteristics of flocculating substances (FS) by A. niger and advance a possible flocculation mechanism for by-product conversion. 36144450 7 46 theme existing 1230:1237 arg1 technologies 1248:1259 existing recovery technologies 1230:1259 existing recovery technologies 1230:1259 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 3 47 theme COD 623:625 arg1 % 727:727 58.85% 722:727 58.85% 722:727 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 47 theme COD 623:625 arg1 rate 636:639 the chemical oxygen demand (COD) removal rate 595:639 the chemical oxygen demand (COD) removal rate 595:639 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 7 48 theme potato 1273:1278 arg1 by-products 1287:1297 converting potato starch by-products 1262:1297 converting potato starch by-products via A. niger 1262:1310 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 7 49 dep fermentation 1319:1330 arg1 liquid 1312:1317 liquid 1312:1317 liquid 1312:1317 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 7 49 dep fermentation 1319:1330 arg1 merits 1332:1337 merits 1332:1337 merits 1332:1337 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 4 50 theme × 941:941 arg1 Da 947:948 1.7741 × 106 Da 934:948 1.7741 × 106 Da 934:948 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 7 51 theme recovery 1239:1246 arg1 technologies 1248:1259 existing recovery technologies 1230:1259 existing recovery technologies 1230:1259 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 7 52 theme converting 1262:1271 arg1 by-products 1287:1297 converting potato starch by-products 1262:1297 converting potato starch by-products via A. niger 1262:1310 However, due to severe pollution problems and resource waste, and deficiencies of existing recovery technologies, converting potato starch by-products via A. niger liquid fermentation merits significant consideration. 36144450 0 53 theme Recovery 74:81 arg1 Biotechnology 46:58 Practical Biotechnology 36:58 Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics 36:147 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 3 54 theme conversion 650:659 arg1 % 727:727 58.85% 722:727 58.85% 722:727 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 54 theme conversion 650:659 arg1 rates 661:665 the conversion rates 646:665 the conversion rates of cellulose, hemicellulose, pectin, and proteins 646:715 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 55 theme demand 615:620 arg1 % 727:727 58.85% 722:727 58.85% 722:727 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 55 theme demand 615:620 arg1 rate 636:639 the chemical oxygen demand (COD) removal rate 595:639 the chemical oxygen demand (COD) removal rate 595:639 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 4 56 theme Da 947:948 arg1 distributions 897:909 two molecular weight distributions 876:909 two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity 876:976 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 0 57 theme Industrial 63:72 arg1 Recovery 74:81 Industrial Recovery 63:81 Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics 63:147 Application of Aspergillus niger in Practical Biotechnology of Industrial Recovery of Potato Starch By-Products and Its Flocculation Characteristics. 36144450 3 58 theme hemicellulose 681:693 arg1 % 727:727 58.85% 722:727 58.85% 722:727 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 58 theme hemicellulose 681:693 arg1 rates 661:665 the conversion rates 646:665 the conversion rates of cellulose, hemicellulose, pectin, and proteins 646:715 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 3 58 theme hemicellulose 681:693 arg1 rate 636:639 the chemical oxygen demand (COD) removal rate 595:639 the chemical oxygen demand (COD) removal rate 595:639 After fermentation, the chemical oxygen demand (COD) removal rate, and the conversion rates of cellulose, hemicellulose, pectin, and proteins were 58.85%, 40.19%, 53.29%, 50.14%, and 37.09%, respectively. 36144450 4 59 theme Da 927:928 arg1 distributions 897:909 two molecular weight distributions 876:909 two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity 876:976 FS was predominantly composed of proteins (45.55%, w/w) and polysaccharides (28.07%, w/w), with two molecular weight distributions of 7.3792 × 106 Da and 1.7741 × 106 Da and temperature sensitivity. 36144450 5 60 theme ionic 1024:1028 arg1 bonding 1030:1036 ionic bonding 1024:1036 ionic bonding 1024:1036 Flocculation was mainly through bridging and ionic bonding, furthermore, sweeping effects may occur during sediment. 35341211 3 0 theme formation 723:731 arg1 period 733:738 the biofilm formation period 711:738 the biofilm formation period 711:738 The interrelationship between the acid production of the biofilm and the fluoride release of the G-Is discs was investigated by analyzing both factors simultaneously during the biofilm formation period. 35341211 4 1 theme microscopic 864:874 arg1 methods 876:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 The composition of the 51 h-old biofilms was then examined using microbiological, biochemical, and confocal laser scanning microscopic methods. 35341211 1 2 theme study 150:154 arg1 aim 138:140 The aim 134:140 The aim of this study 134:154 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 0 3 theme acid 74:77 arg1 production 79:88 acid production 74:88 acid production of Streptococcus mutans 74:112 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 35341211 4 4 theme scanning 855:862 arg1 methods 876:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 The composition of the 51 h-old biofilms was then examined using microbiological, biochemical, and confocal laser scanning microscopic methods. 35341211 1 5 theme cariogenic 227:236 arg1 biofilms 238:245 cariogenic biofilms 227:245 cariogenic biofilms in the slow fluoride release phase 227:280 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 0 6 theme Streptococcus 93:105 arg1 mutans 107:112 Streptococcus mutans 93:112 Streptococcus mutans 93:112 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 35341211 1 7 theme fluoride 330:337 arg1 release 339:345 fluoride release 330:345 fluoride release from G-Is 330:355 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 8 8 dep Conclusions 1305:1315 arg1 suggest 1331:1337 suggest 1331:1337 suggest that G-Is may play a role in preventing the development of secondary caries during the slow fluoride release phase 1331:1452 Conclusions These results suggest that G-Is may play a role in preventing the development of secondary caries during the slow fluoride release phase. 35341211 4 9 theme biochemical 823:833 arg1 methods 876:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 The composition of the 51 h-old biofilms was then examined using microbiological, biochemical, and confocal laser scanning microscopic methods. 35341211 7 10 theme biofilm 1211:1217 arg1 bio-mass 1219:1226 cariogenic biofilm bio-mass 1200:1226 cariogenic biofilm bio-mass 1200:1226 This reciprocal interaction results in the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is. 35341211 2 11 theme mutans 494:499 arg1 biofilms 501:508 51 h-old S. mutans biofilms 482:508 51 h-old S. mutans biofilms 482:508 Methods G-Is discs in the slow fluoride release phase were prepared and 51 h-old S. mutans biofilms were formed on these discs. 35341211 3 12 theme biofilm 715:721 arg1 formation 723:731 biofilm formation 715:731 the biofilm formation period 711:738 The interrelationship between the acid production of the biofilm and the fluoride release of the G-Is discs was investigated by analyzing both factors simultaneously during the biofilm formation period. 35341211 7 13 theme polysaccharides 1170:1184 arg1 formation 1186:1194 extracellular polysaccharides formation 1156:1194 extracellular polysaccharides formation 1156:1194 This reciprocal interaction results in the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is. 35341211 6 14 theme acid 1039:1042 arg1 production 1044:1053 the acid production 1035:1053 the acid production of the cariogenic biofilm 1035:1079 Conversely, G-Is fluoride release inhibits the acid production of the cariogenic biofilm. 35341211 4 15 theme 51 h-old 764:771 arg1 biofilms 773:780 the 51 h-old biofilms 760:780 the 51 h-old biofilms 760:780 The composition of the 51 h-old biofilms was then examined using microbiological, biochemical, and confocal laser scanning microscopic methods. 35341211 6 16 theme biofilm 1073:1079 arg1 production 1044:1053 the acid production 1035:1053 the acid production of the cariogenic biofilm 1035:1079 Conversely, G-Is fluoride release inhibits the acid production of the cariogenic biofilm. 35341211 0 17 theme mutans 107:112 arg1 release 44:50 fluoride release 35:50 fluoride release of glass ionomers 35:68 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 35341211 0 17 theme mutans 107:112 arg1 production 79:88 acid production 74:88 acid production of Streptococcus mutans 74:112 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 35341211 1 18 dep Objectives 123:132 arg1 was 156:158 was 156:158 was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm 156:407 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 6 19 theme cariogenic 1062:1071 arg1 biofilm 1073:1079 the cariogenic biofilm 1058:1079 the cariogenic biofilm 1058:1079 Conversely, G-Is fluoride release inhibits the acid production of the cariogenic biofilm. 35341211 0 20 theme reciprocal 4:13 arg1 interaction 15:25 The reciprocal interaction 0:25 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 0:121 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 35341211 8 21 theme fluoride 1431:1438 arg1 phase 1448:1452 the slow fluoride release phase 1422:1452 the slow fluoride release phase 1422:1452 Conclusions These results suggest that G-Is may play a role in preventing the development of secondary caries during the slow fluoride release phase. 35341211 4 22 theme laser 849:853 arg1 methods 876:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 The composition of the 51 h-old biofilms was then examined using microbiological, biochemical, and confocal laser scanning microscopic methods. 35341211 4 23 theme confocal 840:847 arg1 methods 876:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 The composition of the 51 h-old biofilms was then examined using microbiological, biochemical, and confocal laser scanning microscopic methods. 35341211 7 24 theme reciprocal 1087:1096 arg1 interaction 1098:1108 This reciprocal interaction 1082:1108 This reciprocal interaction 1082:1108 This reciprocal interaction results in the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is. 35341211 7 25 theme extracellular 1156:1168 arg1 formation 1186:1194 extracellular polysaccharides formation 1156:1194 extracellular polysaccharides formation 1156:1194 This reciprocal interaction results in the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is. 35341211 1 26 theme slow 254:257 arg1 phase 276:280 the slow fluoride release phase 250:280 the slow fluoride release phase 250:280 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 1 27 from biofilms 238:245 arg1 phase 276:280 the slow fluoride release phase 250:280 the slow fluoride release phase 250:280 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 5 28 theme < 952:952 arg1 pH 954:955 < pH 5 952:957 < pH 5 952:957 Results Acid production by the cariogenic biofilm, particularly at < pH 5, promotes G-Is fluoride release. 35341211 2 29 theme Methods 410:416 arg1 discs 423:427 Methods G-Is discs 410:427 Methods G-Is discs in the slow fluoride release phase 410:462 Methods G-Is discs in the slow fluoride release phase were prepared and 51 h-old S. mutans biofilms were formed on these discs. 35341211 2 30 theme G-Is 418:421 arg1 discs 423:427 Methods G-Is discs 410:427 Methods G-Is discs in the slow fluoride release phase 410:462 Methods G-Is discs in the slow fluoride release phase were prepared and 51 h-old S. mutans biofilms were formed on these discs. 35341211 1 31 theme fluoride 259:266 arg1 phase 276:280 the slow fluoride release phase 250:280 the slow fluoride release phase 250:280 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 1 32 theme acid 361:364 arg1 production 366:375 acid production 361:375 acid production of Streptococcus mutans biofilm 361:407 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 2 33 theme fluoride 441:448 arg1 phase 458:462 the slow fluoride release phase 432:462 the slow fluoride release phase 432:462 Methods G-Is discs in the slow fluoride release phase were prepared and 51 h-old S. mutans biofilms were formed on these discs. 35341211 1 34 theme action 187:192 arg1 mode 179:182 the mode 175:182 the mode of action of glass ionomers (G-Is) 175:217 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 1 35 theme release 268:274 arg1 phase 276:280 the slow fluoride release phase 250:280 the slow fluoride release phase 250:280 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 7 36 theme cariogenic 1200:1209 arg1 bio-mass 1219:1226 cariogenic biofilm bio-mass 1200:1226 cariogenic biofilm bio-mass 1200:1226 This reciprocal interaction results in the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is. 35341211 7 37 theme secondary 1263:1271 arg1 development 1280:1290 secondary caries development 1263:1290 secondary caries development 1263:1290 This reciprocal interaction results in the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is. 35341211 4 38 theme microbiological 806:820 arg1 methods 876:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 microbiological, biochemical, and confocal laser scanning microscopic methods 806:882 The composition of the 51 h-old biofilms was then examined using microbiological, biochemical, and confocal laser scanning microscopic methods. 35341211 0 39 theme fluoride 35:42 arg1 release 44:50 fluoride release 35:50 fluoride release of glass ionomers 35:68 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 35341211 2 40 theme release 450:456 arg1 phase 458:462 the slow fluoride release phase 432:462 the slow fluoride release phase 432:462 Methods G-Is discs in the slow fluoride release phase were prepared and 51 h-old S. mutans biofilms were formed on these discs. 35341211 3 41 theme fluoride 611:618 arg1 release 620:626 the fluoride release 607:626 the fluoride release of the G-Is discs 607:644 The interrelationship between the acid production of the biofilm and the fluoride release of the G-Is discs was investigated by analyzing both factors simultaneously during the biofilm formation period. 35341211 8 42 theme caries 1408:1413 arg1 development 1383:1393 the development 1379:1393 the development of secondary caries 1379:1413 Conclusions These results suggest that G-Is may play a role in preventing the development of secondary caries during the slow fluoride release phase. 35341211 1 43 theme glass 197:201 arg1 G-Is 213:216 G-Is 213:216 G-Is 213:216 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 1 43 theme glass 197:201 arg1 ionomers 203:210 glass ionomers 197:210 glass ionomers (G-Is) 197:217 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 0 44 theme glass 55:59 arg1 ionomers 61:68 glass ionomers 55:68 glass ionomers 55:68 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 35341211 0 45 dep release 44:50 arg1 biofilm 114:120 biofilm 114:120 biofilm 114:120 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 35341211 2 46 theme slow 436:439 arg1 phase 458:462 the slow fluoride release phase 432:462 the slow fluoride release phase 432:462 Methods G-Is discs in the slow fluoride release phase were prepared and 51 h-old S. mutans biofilms were formed on these discs. 35341211 8 47 theme slow 1426:1429 arg1 phase 1448:1452 the slow fluoride release phase 1422:1452 the slow fluoride release phase 1422:1452 Conclusions These results suggest that G-Is may play a role in preventing the development of secondary caries during the slow fluoride release phase. 35341211 2 48 from discs 423:427 arg1 phase 458:462 the slow fluoride release phase 432:462 the slow fluoride release phase 432:462 Methods G-Is discs in the slow fluoride release phase were prepared and 51 h-old S. mutans biofilms were formed on these discs. 35341211 1 49 theme mutans 394:399 arg1 biofilm 401:407 Streptococcus mutans biofilm 380:407 Streptococcus mutans biofilm 380:407 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 3 50 theme acid 572:575 arg1 production 577:586 the acid production 568:586 the acid production of the biofilm 568:601 The interrelationship between the acid production of the biofilm and the fluoride release of the G-Is discs was investigated by analyzing both factors simultaneously during the biofilm formation period. 35341211 5 51 theme cariogenic 916:925 arg1 biofilm 927:933 the cariogenic biofilm 912:933 the cariogenic biofilm 912:933 Results Acid production by the cariogenic biofilm, particularly at < pH 5, promotes G-Is fluoride release. 35341211 8 52 theme release 1440:1446 arg1 phase 1448:1452 the slow fluoride release phase 1422:1452 the slow fluoride release phase 1422:1452 Conclusions These results suggest that G-Is may play a role in preventing the development of secondary caries during the slow fluoride release phase. 35341211 7 53 theme caries 1273:1278 arg1 development 1280:1290 secondary caries development 1263:1290 secondary caries development 1263:1290 This reciprocal interaction results in the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is. 35341211 7 54 theme virulence 1138:1146 arg1 reduction 1125:1133 the reduction 1121:1133 the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is 1121:1302 This reciprocal interaction results in the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is. 35341211 1 55 theme biofilm 401:407 arg1 production 366:375 acid production 361:375 acid production of Streptococcus mutans biofilm 361:407 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 1 55 theme biofilm 401:407 arg1 release 339:345 fluoride release 330:345 fluoride release from G-Is 330:355 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 5 56 theme fluoride 974:981 arg1 release 983:989 G-Is fluoride release 969:989 G-Is fluoride release 969:989 Results Acid production by the cariogenic biofilm, particularly at < pH 5, promotes G-Is fluoride release. 35341211 7 57 theme development 1280:1290 arg1 potential 1250:1258 the potential 1246:1258 the potential of secondary caries development around G-Is 1246:1302 This reciprocal interaction results in the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is. 35341211 5 58 from pH 954:955 arg1 production 898:907 Results Acid production 885:907 Results Acid production 885:907 Results Acid production by the cariogenic biofilm, particularly at < pH 5, promotes G-Is fluoride release. 35341211 1 59 theme ionomers 203:210 arg1 action 187:192 action 187:192 action of glass ionomers (G-Is) 187:217 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 5 60 theme G-Is 969:972 arg1 release 983:989 G-Is fluoride release 969:989 G-Is fluoride release 969:989 Results Acid production by the cariogenic biofilm, particularly at < pH 5, promotes G-Is fluoride release. 35341211 3 61 theme G-Is 635:638 arg1 discs 640:644 the G-Is discs 631:644 the G-Is discs 631:644 The interrelationship between the acid production of the biofilm and the fluoride release of the G-Is discs was investigated by analyzing both factors simultaneously during the biofilm formation period. 35341211 4 62 theme biofilms 773:780 arg1 composition 745:755 The composition 741:755 The composition of the 51 h-old biofilms 741:780 The composition of the 51 h-old biofilms was then examined using microbiological, biochemical, and confocal laser scanning microscopic methods. 35341211 5 63 theme Acid 893:896 arg1 production 898:907 Results Acid production 885:907 Results Acid production 885:907 Results Acid production by the cariogenic biofilm, particularly at < pH 5, promotes G-Is fluoride release. 35341211 6 64 theme fluoride 1009:1016 arg1 release 1018:1024 G-Is fluoride release 1004:1024 G-Is fluoride release 1004:1024 Conversely, G-Is fluoride release inhibits the acid production of the cariogenic biofilm. 35341211 2 65 theme 51 h-old 482:489 arg1 biofilms 501:508 51 h-old S. mutans biofilms 482:508 51 h-old S. mutans biofilms 482:508 Methods G-Is discs in the slow fluoride release phase were prepared and 51 h-old S. mutans biofilms were formed on these discs. 35341211 3 66 theme discs 640:644 arg1 production 577:586 the acid production 568:586 the acid production of the biofilm 568:601 The interrelationship between the acid production of the biofilm and the fluoride release of the G-Is discs was investigated by analyzing both factors simultaneously during the biofilm formation period. 35341211 3 66 theme discs 640:644 arg1 release 620:626 the fluoride release 607:626 the fluoride release of the G-Is discs 607:644 The interrelationship between the acid production of the biofilm and the fluoride release of the G-Is discs was investigated by analyzing both factors simultaneously during the biofilm formation period. 35341211 5 67 theme Results 885:891 arg1 production 898:907 Results Acid production 885:907 Results Acid production 885:907 Results Acid production by the cariogenic biofilm, particularly at < pH 5, promotes G-Is fluoride release. 35341211 8 68 theme secondary 1398:1406 arg1 caries 1408:1413 secondary caries 1398:1413 secondary caries 1398:1413 Conclusions These results suggest that G-Is may play a role in preventing the development of secondary caries during the slow fluoride release phase. 35341211 6 69 theme G-Is 1004:1007 arg1 release 1018:1024 G-Is fluoride release 1004:1024 G-Is fluoride release 1004:1024 Conversely, G-Is fluoride release inhibits the acid production of the cariogenic biofilm. 35341211 0 70 theme ionomers 61:68 arg1 release 44:50 fluoride release 35:50 fluoride release of glass ionomers 35:68 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 35341211 0 70 theme ionomers 61:68 arg1 production 79:88 acid production 74:88 acid production of Streptococcus mutans 74:112 The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm. 35341211 1 71 theme reciprocal 299:308 arg1 interaction 310:320 the reciprocal interaction 295:320 the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm 295:407 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 3 72 theme biofilm 595:601 arg1 production 577:586 the acid production 568:586 the acid production of the biofilm 568:601 The interrelationship between the acid production of the biofilm and the fluoride release of the G-Is discs was investigated by analyzing both factors simultaneously during the biofilm formation period. 35341211 3 72 theme biofilm 595:601 arg1 release 620:626 the fluoride release 607:626 the fluoride release of the G-Is discs 607:644 The interrelationship between the acid production of the biofilm and the fluoride release of the G-Is discs was investigated by analyzing both factors simultaneously during the biofilm formation period. 35341211 1 73 from G-Is 352:355 arg1 production 366:375 acid production 361:375 acid production of Streptococcus mutans biofilm 361:407 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35341211 1 73 from G-Is 352:355 arg1 release 339:345 fluoride release 330:345 fluoride release from G-Is 330:355 Objectives The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. 35061828 5 0 theme CLSM 1011:1014 arg1 analyses 1016:1023 CLSM analyses 1011:1023 CLSM analyses 1011:1023 CLSM analyses revealed that micro-colonies rich in polysaccharides readily sloughed from the carriers. 35061828 2 1 theme extracellular 531:543 arg1 substance 555:563 extracellular polymeric substance 531:563 extracellular polymeric substance (EPS) 531:569 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 1 theme extracellular 531:543 arg1 EPS 566:568 EPS 566:568 EPS 566:568 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 4 2 theme protein 790:796 arg1 ratio 816:820 the protein to polysaccharide ratio 786:820 the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing 786:897 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 1 3 theme fixed-film 136:145 arg1 IF-SBR 173:178 IF-SBR 173:178 IF-SBR 173:178 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 1 3 theme fixed-film 136:145 arg1 reactor 164:170 a laboratory-scale (LS) integrated fixed-film sequencing batch reactor 101:170 a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) 101:179 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 4 4 theme confocal 927:934 arg1 CLSM 963:966 CLSM 963:966 CLSM 963:966 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 4 4 theme confocal 927:934 arg1 microscopy 951:960 the confocal laser scanning microscopy 923:960 the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining 923:1008 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 2 5 theme suspended 429:437 arg1 MLSS 447:450 MLSS 447:450 MLSS 447:450 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 5 theme suspended 429:437 arg1 solids 439:444 suspended solids 429:444 mixed liquor suspended solids (MLSS) 416:451 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 4 6 theme extracted 755:763 arg1 results 777:783 the extracted EPS content results 751:783 the extracted EPS content results 751:783 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 6 7 theme susceptible 1257:1267 arg1 areas 1236:1240 areas 1236:1240 areas of the biofilm susceptible to sloughing 1236:1280 Live-dead staining revealed areas of the biofilm where the viability of biomass was a contributing factor associated with areas of the biofilm susceptible to sloughing. 35061828 1 8 theme sequencing 147:156 arg1 IF-SBR 173:178 IF-SBR 173:178 IF-SBR 173:178 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 1 8 theme sequencing 147:156 arg1 reactor 164:170 a laboratory-scale (LS) integrated fixed-film sequencing batch reactor 101:170 a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) 101:179 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 4 9 with biofilms 866:873 arg1 sloughing 889:897 biofilm sloughing 881:897 biofilm sloughing 881:897 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 4 10 theme EPS 765:767 arg1 results 777:783 the extracted EPS content results 751:783 the extracted EPS content results 751:783 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 2 11 theme suspended 463:471 arg1 ESS 481:483 ESS 481:483 ESS 481:483 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 11 theme suspended 463:471 arg1 solids 473:478 effluent suspended solids 454:478 effluent suspended solids (ESS) 454:484 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 0 12 from Fate 0:3 arg1 systems 50:56 integrated fixed-film systems 28:56 integrated fixed-film systems 28:56 Fate of sloughed biomass in integrated fixed-film systems. 35061828 2 13 dep liquor 422:427 arg1 MLSS 447:450 MLSS 447:450 MLSS 447:450 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 13 dep liquor 422:427 arg1 solids 439:444 suspended solids 429:444 mixed liquor suspended solids (MLSS) 416:451 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 6 14 theme biofilm 1155:1161 arg1 areas 1142:1146 areas 1142:1146 areas of the biofilm where the viability of biomass was a contributing factor associated with areas of the biofilm susceptible to sloughing 1142:1280 Live-dead staining revealed areas of the biofilm where the viability of biomass was a contributing factor associated with areas of the biofilm susceptible to sloughing. 35061828 7 15 theme IFAS 1325:1328 arg1 samples 1330:1336 FS IFAS samples 1322:1336 FS IFAS samples 1322:1336 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 4 16 theme scanning 942:949 arg1 CLSM 963:966 CLSM 963:966 CLSM 963:966 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 4 16 theme scanning 942:949 arg1 microscopy 951:960 the confocal laser scanning microscopy 923:960 the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining 923:1008 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 2 17 theme effluent 454:461 arg1 ESS 481:483 ESS 481:483 ESS 481:483 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 17 theme effluent 454:461 arg1 solids 473:478 effluent suspended solids 454:478 effluent suspended solids (ESS) 454:484 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 4 18 theme content 769:775 arg1 results 777:783 the extracted EPS content results 751:783 the extracted EPS content results 751:783 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 2 19 from formation 614:622 arg1 IF-SBR 658:663 the LS IF-SBR 651:663 the LS IF-SBR 651:663 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 1 20 theme integrated 236:245 arg1 system 282:287 integrated fixed-film activated sludge (IFAS) system 236:287 integrated fixed-film activated sludge (IFAS) system 236:287 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 4 21 dep ratio 816:820 arg1 to 798:799 to 798:799 to 798:799 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 4 21 dep ratio 816:820 arg1 increased 849:857 increased 849:857 increased in the biofilms, with biofilm sloughing 849:897 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 4 21 dep ratio 816:820 arg1 decreased 822:830 decreased 822:830 decreased in the flocs 822:843 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 6 22 theme contributing 1200:1211 arg1 factor 1213:1218 a contributing factor 1198:1218 a contributing factor associated with areas of the biofilm susceptible to sloughing 1198:1280 Live-dead staining revealed areas of the biofilm where the viability of biomass was a contributing factor associated with areas of the biofilm susceptible to sloughing. 35061828 6 22 theme contributing 1200:1211 arg1 viability 1173:1181 the viability 1169:1181 the viability of biomass 1169:1192 Live-dead staining revealed areas of the biofilm where the viability of biomass was a contributing factor associated with areas of the biofilm susceptible to sloughing. 35061828 1 23 theme batch 158:162 arg1 IF-SBR 173:178 IF-SBR 173:178 IF-SBR 173:178 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 1 23 theme batch 158:162 arg1 reactor 164:170 a laboratory-scale (LS) integrated fixed-film sequencing batch reactor 101:170 a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) 101:179 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 3 24 theme molecular 721:729 arg1 level 731:735 the molecular level 717:735 the molecular level 717:735 In the FS IFAS system, the changes were studied at the molecular level. 35061828 4 25 theme biofilm 881:887 arg1 sloughing 889:897 biofilm sloughing 881:897 biofilm sloughing 881:897 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 1 26 theme biofilm 67:73 arg1 sloughing 75:83 biofilm sloughing 67:83 biofilm sloughing 67:83 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 7 27 theme FS 1322:1323 arg1 samples 1330:1336 FS IFAS samples 1322:1336 FS IFAS samples 1322:1336 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 2 28 theme biofilms 359:366 arg1 index 403:407 sludge volume index 389:407 sludge volume index (SVI) 389:413 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 28 theme biofilms 359:366 arg1 hydrophobicity 496:509 relative hydrophobicity 487:509 relative hydrophobicity 487:509 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 28 theme biofilms 359:366 arg1 solids 473:478 effluent suspended solids 454:478 effluent suspended solids (ESS) 454:484 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 28 theme biofilms 359:366 arg1 properties 345:354 the properties 341:354 the properties 341:354 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 28 theme biofilms 359:366 arg1 composition 516:526 composition 516:526 composition of extracellular polymeric substance (EPS) 516:569 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 28 theme biofilms 359:366 arg1 liquor 422:427 mixed liquor suspended solids (MLSS) 416:451 mixed liquor suspended solids (MLSS) 416:451 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 7 29 theme greater 1347:1353 arg1 diversity 1355:1363 greater diversity 1347:1363 greater diversity (α-diversity) in biofilms compared to flocs 1347:1407 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 7 29 theme greater 1347:1353 arg1 α-diversity 1366:1376 α-diversity 1366:1376 α-diversity 1366:1376 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 2 30 theme substance 555:563 arg1 index 403:407 sludge volume index 389:407 sludge volume index (SVI) 389:413 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 30 theme substance 555:563 arg1 SVI 410:412 SVI 410:412 SVI 410:412 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 30 theme substance 555:563 arg1 hydrophobicity 496:509 relative hydrophobicity 487:509 relative hydrophobicity 487:509 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 30 theme substance 555:563 arg1 solids 473:478 effluent suspended solids 454:478 effluent suspended solids (ESS) 454:484 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 30 theme substance 555:563 arg1 ESS 481:483 ESS 481:483 ESS 481:483 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 30 theme substance 555:563 arg1 composition 516:526 composition 516:526 composition of extracellular polymeric substance (EPS) 516:569 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 30 theme substance 555:563 arg1 liquor 422:427 mixed liquor suspended solids (MLSS) 416:451 mixed liquor suspended solids (MLSS) 416:451 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 9 31 theme suspended 1718:1726 arg1 biomass 1728:1734 the suspended biomass 1714:1734 the suspended biomass 1714:1734 Microbial population dynamics revealed that bacteria known for denitrification (for example, Comamonadaceae) detached from the biofilms during sloughing, readily associated with the suspended biomass, and were retained in the bioreactors. 35061828 1 32 theme sloughing 75:83 arg1 Fate 59:62 Fate 59:62 Fate of biofilm sloughing 59:83 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 8 33 theme Biofilm 1410:1416 arg1 sloughing 1418:1426 Biofilm sloughing 1410:1426 Biofilm sloughing 1410:1426 Biofilm sloughing resulted in a decrease in diversity in biofilms and a corresponding increase in the flocs during sloughing. 35061828 2 34 from flocs 642:646 arg1 IF-SBR 658:663 the LS IF-SBR 651:663 the LS IF-SBR 651:663 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 1 35 theme fixed-film 247:256 arg1 system 282:287 integrated fixed-film activated sludge (IFAS) system 236:287 integrated fixed-film activated sludge (IFAS) system 236:287 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 2 36 theme polymeric 545:553 arg1 substance 555:563 extracellular polymeric substance 531:563 extracellular polymeric substance (EPS) 531:569 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 36 theme polymeric 545:553 arg1 EPS 566:568 EPS 566:568 EPS 566:568 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 4 37 dep complemented 905:916 arg1 ratio 816:820 the protein to polysaccharide ratio 786:820 the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing 786:897 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 9 38 dep known 1589:1593 arg1 Comamonadaceae 1629:1642 Comamonadaceae 1629:1642 Comamonadaceae 1629:1642 Microbial population dynamics revealed that bacteria known for denitrification (for example, Comamonadaceae) detached from the biofilms during sloughing, readily associated with the suspended biomass, and were retained in the bioreactors. 35061828 9 38 dep known 1589:1593 arg1 bacteria 1580:1587 bacteria 1580:1587 bacteria known for denitrification (for example, Comamonadaceae) 1580:1643 Microbial population dynamics revealed that bacteria known for denitrification (for example, Comamonadaceae) detached from the biofilms during sloughing, readily associated with the suspended biomass, and were retained in the bioreactors. 35061828 4 39 theme molecular 982:990 arg1 staining 1001:1008 molecular specific staining 982:1008 molecular specific staining 982:1008 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 6 40 theme biomass 1186:1192 arg1 factor 1213:1218 a contributing factor 1198:1218 a contributing factor associated with areas of the biofilm susceptible to sloughing 1198:1280 Live-dead staining revealed areas of the biofilm where the viability of biomass was a contributing factor associated with areas of the biofilm susceptible to sloughing. 35061828 6 40 theme biomass 1186:1192 arg1 viability 1173:1181 the viability 1169:1181 the viability of biomass 1169:1192 Live-dead staining revealed areas of the biofilm where the viability of biomass was a contributing factor associated with areas of the biofilm susceptible to sloughing. 35061828 0 41 theme biomass 17:23 arg1 Fate 0:3 Fate 0:3 Fate of sloughed biomass in integrated fixed-film systems. 0:57 Fate of sloughed biomass in integrated fixed-film systems. 35061828 1 42 theme activated 258:266 arg1 system 282:287 integrated fixed-film activated sludge (IFAS) system 236:287 integrated fixed-film activated sludge (IFAS) system 236:287 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 6 43 theme biofilm 1249:1255 arg1 areas 1236:1240 areas 1236:1240 areas of the biofilm susceptible to sloughing 1236:1280 Live-dead staining revealed areas of the biofilm where the viability of biomass was a contributing factor associated with areas of the biofilm susceptible to sloughing. 35061828 2 44 theme biofilm 592:598 arg1 sloughing 600:608 biofilm sloughing 592:608 biofilm sloughing 592:608 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 9 45 theme population 1546:1555 arg1 dynamics 1557:1564 Microbial population dynamics 1536:1564 Microbial population dynamics 1536:1564 Microbial population dynamics revealed that bacteria known for denitrification (for example, Comamonadaceae) detached from the biofilms during sloughing, readily associated with the suspended biomass, and were retained in the bioreactors. 35061828 7 46 theme rRNA 1287:1290 arg1 Illumina 1309:1316 Illumina 1309:1316 Illumina 1309:1316 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 7 46 theme rRNA 1287:1290 arg1 sequencing 1297:1306 16S rRNA gene sequencing 1283:1306 16S rRNA gene sequencing (Illumina) of FS IFAS samples 1283:1336 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 2 47 theme sludge 389:394 arg1 SVI 410:412 SVI 410:412 SVI 410:412 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 47 theme sludge 389:394 arg1 index 403:407 sludge volume index 389:407 sludge volume index (SVI) 389:413 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 48 theme volume 396:401 arg1 SVI 410:412 SVI 410:412 SVI 410:412 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 48 theme volume 396:401 arg1 index 403:407 sludge volume index 389:407 sludge volume index (SVI) 389:413 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 1 49 theme sludge 268:273 arg1 system 282:287 integrated fixed-film activated sludge (IFAS) system 236:287 integrated fixed-film activated sludge (IFAS) system 236:287 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 4 50 theme polysaccharide 801:814 arg1 ratio 816:820 the protein to polysaccharide ratio 786:820 the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing 786:897 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 9 51 theme Microbial 1536:1544 arg1 dynamics 1557:1564 Microbial population dynamics 1536:1564 Microbial population dynamics 1536:1564 Microbial population dynamics revealed that bacteria known for denitrification (for example, Comamonadaceae) detached from the biofilms during sloughing, readily associated with the suspended biomass, and were retained in the bioreactors. 35061828 0 52 theme integrated 28:37 arg1 systems 50:56 integrated fixed-film systems 28:56 integrated fixed-film systems 28:56 Fate of sloughed biomass in integrated fixed-film systems. 35061828 7 53 from diversity 1355:1363 arg1 biofilms 1382:1389 biofilms 1382:1389 biofilms compared to flocs 1382:1407 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 8 54 from increase 1496:1503 arg1 biofilms 1467:1474 biofilms 1467:1474 biofilms 1467:1474 Biofilm sloughing resulted in a decrease in diversity in biofilms and a corresponding increase in the flocs during sloughing. 35061828 8 54 from increase 1496:1503 arg1 diversity 1454:1462 diversity 1454:1462 diversity 1454:1462 Biofilm sloughing resulted in a decrease in diversity in biofilms and a corresponding increase in the flocs during sloughing. 35061828 8 54 from increase 1496:1503 arg1 flocs 1512:1516 the flocs 1508:1516 the flocs 1508:1516 Biofilm sloughing resulted in a decrease in diversity in biofilms and a corresponding increase in the flocs during sloughing. 35061828 2 55 from IF-SBR 658:663 arg1 sloughing 600:608 biofilm sloughing 592:608 biofilm sloughing 592:608 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 55 from IF-SBR 658:663 arg1 formation 614:622 formation 614:622 formation of large granular flocs in the LS IF-SBR 614:663 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 5 56 from rich 1054:1057 arg1 polysaccharides 1062:1076 polysaccharides 1062:1076 polysaccharides readily sloughed from the carriers 1062:1111 CLSM analyses revealed that micro-colonies rich in polysaccharides readily sloughed from the carriers. 35061828 4 57 theme specific 992:999 arg1 staining 1001:1008 molecular specific staining 982:1008 molecular specific staining 982:1008 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 1 58 theme synthetic 190:198 arg1 wastewater 200:209 synthetic wastewater 190:209 synthetic wastewater 190:209 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 2 59 theme mixed 416:420 arg1 liquor 422:427 mixed liquor suspended solids (MLSS) 416:451 mixed liquor suspended solids (MLSS) 416:451 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 1 60 theme IFAS 276:279 arg1 system 282:287 integrated fixed-film activated sludge (IFAS) system 236:287 integrated fixed-film activated sludge (IFAS) system 236:287 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 8 61 from decrease 1442:1449 arg1 biofilms 1467:1474 biofilms 1467:1474 biofilms 1467:1474 Biofilm sloughing resulted in a decrease in diversity in biofilms and a corresponding increase in the flocs during sloughing. 35061828 8 61 from decrease 1442:1449 arg1 diversity 1454:1462 diversity 1454:1462 diversity 1454:1462 Biofilm sloughing resulted in a decrease in diversity in biofilms and a corresponding increase in the flocs during sloughing. 35061828 8 61 from decrease 1442:1449 arg1 flocs 1512:1516 the flocs 1508:1516 the flocs 1508:1516 Biofilm sloughing resulted in a decrease in diversity in biofilms and a corresponding increase in the flocs during sloughing. 35061828 7 62 theme gene 1292:1295 arg1 Illumina 1309:1316 Illumina 1309:1316 Illumina 1309:1316 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 7 62 theme gene 1292:1295 arg1 sequencing 1297:1306 16S rRNA gene sequencing 1283:1306 16S rRNA gene sequencing (Illumina) of FS IFAS samples 1283:1336 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 2 63 theme flocs 642:646 arg1 sloughing 600:608 biofilm sloughing 592:608 biofilm sloughing 592:608 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 63 theme flocs 642:646 arg1 formation 614:622 formation 614:622 formation of large granular flocs in the LS IF-SBR 614:663 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 64 theme flocs 372:376 arg1 index 403:407 sludge volume index 389:407 sludge volume index (SVI) 389:413 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 64 theme flocs 372:376 arg1 hydrophobicity 496:509 relative hydrophobicity 487:509 relative hydrophobicity 487:509 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 64 theme flocs 372:376 arg1 solids 473:478 effluent suspended solids 454:478 effluent suspended solids (ESS) 454:484 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 64 theme flocs 372:376 arg1 properties 345:354 the properties 341:354 the properties 341:354 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 64 theme flocs 372:376 arg1 composition 516:526 composition 516:526 composition of extracellular polymeric substance (EPS) 516:569 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 64 theme flocs 372:376 arg1 liquor 422:427 mixed liquor suspended solids (MLSS) 416:451 mixed liquor suspended solids (MLSS) 416:451 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 3 65 theme FS 673:674 arg1 system 681:686 the FS IFAS system 669:686 the FS IFAS system 669:686 In the FS IFAS system, the changes were studied at the molecular level. 35061828 2 66 theme granular 633:640 arg1 flocs 642:646 large granular flocs 627:646 large granular flocs in the LS IF-SBR 627:663 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 0 67 theme fixed-film 39:48 arg1 systems 50:56 integrated fixed-film systems 28:56 integrated fixed-film systems 28:56 Fate of sloughed biomass in integrated fixed-film systems. 35061828 3 68 theme IFAS 676:679 arg1 system 681:686 the FS IFAS system 669:686 the FS IFAS system 669:686 In the FS IFAS system, the changes were studied at the molecular level. 35061828 7 69 theme 16S 1283:1285 arg1 Illumina 1309:1316 Illumina 1309:1316 Illumina 1309:1316 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 7 69 theme 16S 1283:1285 arg1 sequencing 1297:1306 16S rRNA gene sequencing 1283:1306 16S rRNA gene sequencing (Illumina) of FS IFAS samples 1283:1336 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 2 70 theme large 627:631 arg1 flocs 642:646 large granular flocs 627:646 large granular flocs in the LS IF-SBR 627:663 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 1 71 theme laboratory-scale 103:118 arg1 IF-SBR 173:178 IF-SBR 173:178 IF-SBR 173:178 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 1 71 theme laboratory-scale 103:118 arg1 reactor 164:170 a laboratory-scale (LS) integrated fixed-film sequencing batch reactor 101:170 a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) 101:179 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 2 72 theme relative 487:494 arg1 hydrophobicity 496:509 relative hydrophobicity 487:509 relative hydrophobicity 487:509 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 6 73 theme Live-dead 1114:1122 arg1 staining 1124:1131 Live-dead staining 1114:1131 Live-dead staining 1114:1131 Live-dead staining revealed areas of the biofilm where the viability of biomass was a contributing factor associated with areas of the biofilm susceptible to sloughing. 35061828 5 74 from polysaccharides 1062:1076 arg1 rich 1054:1057 rich 1054:1057 rich 1054:1057 CLSM analyses revealed that micro-colonies rich in polysaccharides readily sloughed from the carriers. 35061828 1 75 dep laboratory-scale 103:118 arg1 LS 121:122 LS 121:122 LS 121:122 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 8 76 theme corresponding 1482:1494 arg1 increase 1496:1503 a corresponding increase 1480:1503 a corresponding increase in the flocs during sloughing 1480:1533 Biofilm sloughing resulted in a decrease in diversity in biofilms and a corresponding increase in the flocs during sloughing. 35061828 7 77 theme samples 1330:1336 arg1 Illumina 1309:1316 Illumina 1309:1316 Illumina 1309:1316 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 7 77 theme samples 1330:1336 arg1 sequencing 1297:1306 16S rRNA gene sequencing 1283:1306 16S rRNA gene sequencing (Illumina) of FS IFAS samples 1283:1336 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. 35061828 2 78 theme LS 655:656 arg1 IF-SBR 658:663 the LS IF-SBR 651:663 the LS IF-SBR 651:663 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 2 79 from sloughing 600:608 arg1 IF-SBR 658:663 the LS IF-SBR 651:663 the LS IF-SBR 651:663 It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. 35061828 1 80 theme municipal 298:306 arg1 wastewater 308:317 municipal wastewater 298:317 municipal wastewater 298:317 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 0 81 theme sloughed 8:15 arg1 biomass 17:23 sloughed biomass 8:23 sloughed biomass 8:23 Fate of sloughed biomass in integrated fixed-film systems. 35061828 1 82 theme integrated 125:134 arg1 IF-SBR 173:178 IF-SBR 173:178 IF-SBR 173:178 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 1 82 theme integrated 125:134 arg1 reactor 164:170 a laboratory-scale (LS) integrated fixed-film sequencing batch reactor 101:170 a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) 101:179 Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. 35061828 4 83 theme laser 936:940 arg1 CLSM 963:966 CLSM 963:966 CLSM 963:966 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 4 83 theme laser 936:940 arg1 microscopy 951:960 the confocal laser scanning microscopy 923:960 the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining 923:1008 For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. 35061828 9 84 dep detached 1645:1652 arg1 associated 1698:1707 associated 1698:1707 associated with the suspended biomass 1698:1734 Microbial population dynamics revealed that bacteria known for denitrification (for example, Comamonadaceae) detached from the biofilms during sloughing, readily associated with the suspended biomass, and were retained in the bioreactors. 36235941 12 0 theme diffraction 1623:1633 arg1 analysis 1635:1642 till 251.4 °C. X-ray diffraction analysis 1602:1642 till 251.4 °C. X-ray diffraction analysis 1602:1642 The EPS is thermally stable till 251.4 °C. X-ray diffraction analysis confirmed the semicrystalline (54.2%) nature of the EPS. 36235941 6 1 theme surface 783:789 arg1 roughness 791:799 a surface roughness 781:799 a surface roughness of 84.85 nm 781:811 AFM analysis revealed spike-like lumps with a surface roughness of 84.85 nm. 36235941 11 2 theme -β-D-Xylp- 1524:1533 arg1 -β-D-Ribp- 1558:1567 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp- 1433:1567 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp- 1433:1567 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 7 3 theme zeta 818:821 arg1 value 833:837 The zeta potential value 814:837 The zeta potential value of −10 mV 814:847 The zeta potential value of −10 mV indicates the anionic nature of the EPS. 36235941 13 4 theme water 1739:1743 arg1 solubility 1745:1754 significant water solubility 1727:1754 significant water solubility (76.5%) 1727:1762 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 4 theme water 1739:1743 arg1 % 1761:1761 76.5% 1757:1761 76.5% 1757:1761 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 12 5 theme till 1602:1605 arg1 analysis 1635:1642 till 251.4 °C. X-ray diffraction analysis 1602:1642 till 251.4 °C. X-ray diffraction analysis 1602:1642 The EPS is thermally stable till 251.4 °C. X-ray diffraction analysis confirmed the semicrystalline (54.2%) nature of the EPS. 36235941 11 6 theme α- 1364:1365 arg1 composition 1330:1340 the monomer composition 1318:1340 the monomer composition 1318:1340 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 6 theme α- 1364:1365 arg1 existence 1347:1355 the existence 1343:1355 the existence of two α- and six β-glycosidic linkages 1343:1395 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 6 theme α- 1364:1365 arg1 unit 1425:1428 the branched repeating unit 1402:1428 the branched repeating unit 1402:1428 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 6 7 with lumps 770:774 arg1 roughness 791:799 a surface roughness 781:799 a surface roughness of 84.85 nm 781:811 AFM analysis revealed spike-like lumps with a surface roughness of 84.85 nm. 36235941 13 8 dep cytocompatibility 1879:1895 arg1 % 1917:1917 cell viability > 80% 1898:1917 cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells 1898:1958 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 9 theme coagulation 1999:2009 arg1 time 2011:2014 coagulation time 1999:2014 coagulation time in APTT and PT tests 1999:2035 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 2 10 theme present 330:336 arg1 study 338:342 the present study 326:342 the present study 326:342 In this direction, the present study aims to explore the structure and biocompatibility of the EPS produced by Virgibacillus dokdonensis VITP14. 36235941 12 11 theme EPS 1696:1698 arg1 nature 1682:1687 the semicrystalline (54.2%) nature 1654:1687 the semicrystalline (54.2%) nature of the EPS 1654:1698 The EPS is thermally stable till 251.4 °C. X-ray diffraction analysis confirmed the semicrystalline (54.2%) nature of the EPS. 36235941 0 12 theme Coast 165:169 arg1 Saltern 148:154 the Saltern 144:154 the Saltern of Kumta Coast 144:169 Molecular Characterization and Biocompatibility of Exopolysaccharide Produced by Moderately Halophilic Bacterium Virgibacillus dokdonensis from the Saltern of Kumta Coast. 36235941 13 13 theme protection 1856:1865 arg1 hemocompatibility 1825:1841 hemocompatibility 1825:1841 hemocompatibility (erythrocyte protection > 87%) 1825:1872 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 13 theme protection 1856:1865 arg1 % 1871:1871 erythrocyte protection > 87% 1844:1871 erythrocyte protection > 87% 1844:1871 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 14 theme higher 1964:1969 arg1 concentrations 1971:1984 higher concentrations 1964:1984 higher concentrations 1964:1984 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 9 15 theme FTIR 1113:1116 arg1 spectrum 1118:1125 The FTIR spectrum 1109:1125 The FTIR spectrum 1109:1125 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 11 16 theme NMR 1296:1298 arg1 analysis 1300:1307 NMR analysis 1296:1307 NMR analysis 1296:1307 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 5 17 theme EDX 723:725 arg1 analysis 727:734 SEM and EDX analysis 715:734 analysis 727:734 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 13 18 theme emulsifying 1798:1808 arg1 index 1810:1814 emulsifying index 1798:1814 emulsifying index (66.8%) 1798:1822 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 18 theme emulsifying 1798:1808 arg1 % 1821:1821 66.8% 1817:1821 66.8% 1817:1821 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 14 19 theme VITP14 2095:2100 arg1 EPS 2102:2104 VITP14 EPS 2095:2104 VITP14 EPS 2095:2104 Our research unveils the significant biocompatibility of VITP14 EPS for synthesizing a variety of biomaterials. 36235941 10 20 theme molecular 1258:1266 arg1 weight 1268:1273 an average molecular weight 1247:1273 an average molecular weight of 555 kDa 1247:1284 The polymer has an average molecular weight of 555 kDa. 36235941 12 21 theme semicrystalline 1658:1672 arg1 nature 1682:1687 the semicrystalline (54.2%) nature 1654:1687 the semicrystalline (54.2%) nature of the EPS 1654:1698 The EPS is thermally stable till 251.4 °C. X-ray diffraction analysis confirmed the semicrystalline (54.2%) nature of the EPS. 36235941 11 22 theme monomer 1322:1328 arg1 composition 1330:1340 the monomer composition 1318:1340 the monomer composition 1318:1340 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 0 23 theme Bacterium 103:111 arg1 dokdonensis 127:137 Moderately Halophilic Bacterium Virgibacillus dokdonensis 81:137 Moderately Halophilic Bacterium Virgibacillus dokdonensis 81:137 Molecular Characterization and Biocompatibility of Exopolysaccharide Produced by Moderately Halophilic Bacterium Virgibacillus dokdonensis from the Saltern of Kumta Coast. 36235941 9 24 theme functional 1153:1162 arg1 groups/bonds 1164:1175 functional groups/bonds 1153:1175 functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O) 1153:1228 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 1 25 theme natural 183:189 arg1 polysaccharides 191:205 natural polysaccharides 183:205 natural polysaccharides 183:205 The use of natural polysaccharides as biomaterials is gaining importance in tissue engineering due to their inherent biocompatibility. 36235941 9 26 theme typical 1177:1183 arg1 groups/bonds 1164:1175 functional groups/bonds 1153:1175 functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O) 1153:1228 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 5 27 theme elemental 642:650 arg1 composition 652:662 elemental composition 642:662 elemental composition 642:662 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 13 28 theme HaCaT 1948:1952 arg1 cells 1954:1958 RAW264.7 and keratinocyte HaCaT cells 1922:1958 cells 1954:1958 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 10 29 theme kDa 1282:1284 arg1 weight 1268:1273 an average molecular weight 1247:1273 an average molecular weight of 555 kDa 1247:1284 The polymer has an average molecular weight of 555 kDa. 36235941 5 30 theme SEM 715:717 arg1 analysis 727:734 SEM and EDX analysis 715:734 analysis 727:734 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 11 31 dep [β-D-Xylp- 1506:1515 arg1 2 1504:1504 2 1504:1504 2 1504:1504 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 7 32 theme EPS 885:887 arg1 nature 871:876 the anionic nature 859:876 the anionic nature of the EPS 859:887 The zeta potential value of −10 mV indicates the anionic nature of the EPS. 36235941 0 33 theme Molecular 0:8 arg1 Characterization 10:25 Molecular Characterization 0:25 Molecular Characterization 0:25 Molecular Characterization and Biocompatibility of Exopolysaccharide Produced by Moderately Halophilic Bacterium Virgibacillus dokdonensis from the Saltern of Kumta Coast. 36235941 5 34 theme porous 612:617 arg1 structure 628:636 porous web-like structure 612:636 porous web-like structure 612:636 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 11 35 dep -β-D-Xylp- 1524:1533 arg1 -β-D-Frup- 1489:1498 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup- 1433:1498 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4) 1433:1522 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 35 dep -β-D-Xylp- 1524:1533 arg1 [β-D-Xylp- 1506:1515 2 → 2)[β-D-Xylp-(1 → 4 1500:1521 2 → 2)[β-D-Xylp-(1 → 4 1500:1521 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 35 dep -β-D-Xylp- 1524:1533 arg1 → 1537:1537 1 → 6 1535:1539 1 → 6 1535:1539 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 4 36 theme gel 568:570 arg1 methods 599:605 gel permeation chromatographic methods 568:605 gel permeation chromatographic methods 568:605 The EPS was purified using ion exchange and gel permeation chromatographic methods. 36235941 4 37 theme chromatographic 583:597 arg1 methods 599:605 gel permeation chromatographic methods 568:605 gel permeation chromatographic methods 568:605 The EPS was purified using ion exchange and gel permeation chromatographic methods. 36235941 10 38 contain has 1243:1245 arg2 weight 1268:1273 an average molecular weight 1247:1273 an average molecular weight of 555 kDa 1247:1284 The polymer has an average molecular weight of 555 kDa. 36235941 10 38 contain has 1243:1245 arg1 polymer 1235:1241 The polymer 1231:1241 The polymer 1231:1241 The polymer has an average molecular weight of 555 kDa. 36235941 13 39 theme viability 1903:1911 arg1 % 1917:1917 cell viability > 80% 1898:1917 cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells 1898:1958 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 9 40 dep EPSs 1188:1191 arg1 P=O 1225:1227 P=O 1225:1227 P=O 1225:1227 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 9 40 dep EPSs 1188:1191 arg1 EPSs 1188:1191 EPSs 1188:1191 EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O) 1188:1228 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 9 40 dep EPSs 1188:1191 arg1 C-O-H 1204:1208 C-O-H 1204:1208 C-O-H 1204:1208 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 9 40 dep EPSs 1188:1191 arg1 C-O 1211:1213 C-O 1211:1213 C-O 1211:1213 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 9 40 dep EPSs 1188:1191 arg1 O-H 1194:1196 O-H 1194:1196 O-H 1194:1196 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 9 40 dep EPSs 1188:1191 arg1 C-H 1199:1201 C-H 1199:1201 C-H 1199:1201 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 9 40 dep EPSs 1188:1191 arg1 S=O 1216:1218 S=O 1216:1218 S=O 1216:1218 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 3 41 theme fermentation 510:521 arg1 h 505:505 96 h 502:505 96 h of fermentation 502:521 This marine bacterium produces 17.3 g/L of EPS at 96 h of fermentation. 36235941 13 42 theme water-holding 1765:1777 arg1 capacity 1779:1786 water-holding capacity 1765:1786 water-holding capacity (266.8%) 1765:1795 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 42 theme water-holding 1765:1777 arg1 % 1794:1794 266.8% 1789:1794 266.8% 1789:1794 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 6 43 theme nm 810:811 arg1 roughness 791:799 a surface roughness 781:799 a surface roughness of 84.85 nm 781:811 AFM analysis revealed spike-like lumps with a surface roughness of 84.85 nm. 36235941 6 44 theme spike-like 759:768 arg1 lumps 770:774 spike-like lumps 759:774 spike-like lumps with a surface roughness of 84.85 nm 759:811 AFM analysis revealed spike-like lumps with a surface roughness of 84.85 nm. 36235941 11 45 theme β-glycosidic 1375:1386 arg1 linkages 1388:1395 six β-glycosidic linkages 1371:1395 six β-glycosidic linkages 1371:1395 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 8 46 theme molecular 898:906 arg1 characterization 908:923 Initial molecular characterization 890:923 Initial molecular characterization 890:923 Initial molecular characterization showed that the EPS is a heteropolysaccharide composed of glucose (25.8%), ribose (18.6%), fructose (31.5%), and xylose (24%), which are the monosaccharide units in the HPLC analysis. 36235941 5 47 dep structure 628:636 arg1 C 665:665 C 665:665 C 665:665 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 5 47 dep structure 628:636 arg1 O 668:668 O 668:668 O 668:668 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 5 47 dep structure 628:636 arg1 P 679:679 P 679:679 P 679:679 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 5 47 dep structure 628:636 arg1 S 682:682 S 682:682 S 682:682 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 5 47 dep structure 628:636 arg1 Na 671:672 Na 671:672 Na 671:672 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 5 47 dep structure 628:636 arg1 The 608:610 The 608:610 The 608:610 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 5 47 dep structure 628:636 arg1 Mg 675:676 Mg 675:676 Mg 675:676 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 11 48 theme repeating 1415:1423 arg1 unit 1425:1428 the branched repeating unit 1402:1428 the branched repeating unit 1402:1428 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 2 49 theme EPS 402:404 arg1 structure 364:372 structure 364:372 structure 364:372 In this direction, the present study aims to explore the structure and biocompatibility of the EPS produced by Virgibacillus dokdonensis VITP14. 36235941 2 49 theme EPS 402:404 arg1 biocompatibility 378:393 biocompatibility 378:393 biocompatibility 378:393 In this direction, the present study aims to explore the structure and biocompatibility of the EPS produced by Virgibacillus dokdonensis VITP14. 36235941 7 50 theme mV 846:847 arg1 value 833:837 The zeta potential value 814:837 The zeta potential value of −10 mV 814:847 The zeta potential value of −10 mV indicates the anionic nature of the EPS. 36235941 1 51 theme inherent 280:287 arg1 biocompatibility 289:304 their inherent biocompatibility 274:304 their inherent biocompatibility 274:304 The use of natural polysaccharides as biomaterials is gaining importance in tissue engineering due to their inherent biocompatibility. 36235941 12 52 theme X-ray 1617:1621 arg1 analysis 1635:1642 till 251.4 °C. X-ray diffraction analysis 1602:1642 till 251.4 °C. X-ray diffraction analysis 1602:1642 The EPS is thermally stable till 251.4 °C. X-ray diffraction analysis confirmed the semicrystalline (54.2%) nature of the EPS. 36235941 13 53 theme significant 1727:1737 arg1 solubility 1745:1754 significant water solubility 1727:1754 significant water solubility (76.5%) 1727:1762 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 53 theme significant 1727:1737 arg1 % 1761:1761 76.5% 1757:1761 76.5% 1757:1761 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 54 theme APTT 2019:2022 arg1 tests 2031:2035 APTT and PT tests 2019:2035 tests 2031:2035 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 7 55 theme potential 823:831 arg1 value 833:837 The zeta potential value 814:837 The zeta potential value of −10 mV 814:847 The zeta potential value of −10 mV indicates the anionic nature of the EPS. 36235941 1 56 theme polysaccharides 191:205 arg1 use 176:178 The use 172:178 The use of natural polysaccharides as biomaterials 172:221 The use of natural polysaccharides as biomaterials is gaining importance in tissue engineering due to their inherent biocompatibility. 36235941 8 57 from units 1081:1085 arg1 analysis 1099:1106 the HPLC analysis 1090:1106 the HPLC analysis 1090:1106 Initial molecular characterization showed that the EPS is a heteropolysaccharide composed of glucose (25.8%), ribose (18.6%), fructose (31.5%), and xylose (24%), which are the monosaccharide units in the HPLC analysis. 36235941 8 58 theme HPLC 1094:1097 arg1 analysis 1099:1106 the HPLC analysis 1090:1106 the HPLC analysis 1090:1106 Initial molecular characterization showed that the EPS is a heteropolysaccharide composed of glucose (25.8%), ribose (18.6%), fructose (31.5%), and xylose (24%), which are the monosaccharide units in the HPLC analysis. 36235941 11 59 theme [α-D-Xylp- 1437:1446 arg1 -β-D-Frup- 1489:1498 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup- 1433:1498 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4) 1433:1522 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 59 theme [α-D-Xylp- 1437:1446 arg1 [β-D-Xylp- 1506:1515 2 → 2)[β-D-Xylp-(1 → 4 1500:1521 2 → 2)[β-D-Xylp-(1 → 4 1500:1521 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 13 60 theme PT 2028:2029 arg1 tests 2031:2035 APTT and PT tests 2019:2035 tests 2031:2035 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 11 61 theme → 1502:1502 arg1 -β-D-Frup- 1489:1498 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup- 1433:1498 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4) 1433:1522 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 61 theme → 1502:1502 arg1 [β-D-Xylp- 1506:1515 2 → 2)[β-D-Xylp-(1 → 4 1500:1521 2 → 2)[β-D-Xylp-(1 → 4 1500:1521 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 6 62 theme AFM 737:739 arg1 analysis 741:748 AFM analysis 737:748 AFM analysis 737:748 AFM analysis revealed spike-like lumps with a surface roughness of 84.85 nm. 36235941 13 63 theme erythrocyte 1844:1854 arg1 hemocompatibility 1825:1841 hemocompatibility 1825:1841 hemocompatibility (erythrocyte protection > 87%) 1825:1872 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 63 theme erythrocyte 1844:1854 arg1 % 1871:1871 erythrocyte protection > 87% 1844:1871 erythrocyte protection > 87% 1844:1871 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 8 64 theme monosaccharide 1066:1079 arg1 EPS 941:943 the EPS 937:943 the EPS 937:943 Initial molecular characterization showed that the EPS is a heteropolysaccharide composed of glucose (25.8%), ribose (18.6%), fructose (31.5%), and xylose (24%), which are the monosaccharide units in the HPLC analysis. 36235941 8 64 theme monosaccharide 1066:1079 arg1 units 1081:1085 the monosaccharide units 1062:1085 the monosaccharide units in the HPLC analysis 1062:1106 Initial molecular characterization showed that the EPS is a heteropolysaccharide composed of glucose (25.8%), ribose (18.6%), fructose (31.5%), and xylose (24%), which are the monosaccharide units in the HPLC analysis. 36235941 8 64 theme monosaccharide 1066:1079 arg1 heteropolysaccharide 950:969 a heteropolysaccharide 948:969 a heteropolysaccharide 948:969 Initial molecular characterization showed that the EPS is a heteropolysaccharide composed of glucose (25.8%), ribose (18.6%), fructose (31.5%), and xylose (24%), which are the monosaccharide units in the HPLC analysis. 36235941 14 65 theme biomaterials 2136:2147 arg1 biomaterials 2136:2147 biomaterials 2136:2147 biomaterials 2136:2147 Our research unveils the significant biocompatibility of VITP14 EPS for synthesizing a variety of biomaterials. 36235941 14 65 theme biomaterials 2136:2147 arg1 variety 2125:2131 a variety 2123:2131 a variety of biomaterials 2123:2147 Our research unveils the significant biocompatibility of VITP14 EPS for synthesizing a variety of biomaterials. 36235941 13 66 theme keratinocyte 1935:1946 arg1 cells 1954:1958 RAW264.7 and keratinocyte HaCaT cells 1922:1958 cells 1954:1958 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 67 from % 1917:1917 arg1 cells 1954:1958 RAW264.7 and keratinocyte HaCaT cells 1922:1958 cells 1954:1958 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 0 68 theme Halophilic 92:101 arg1 dokdonensis 127:137 Moderately Halophilic Bacterium Virgibacillus dokdonensis 81:137 Moderately Halophilic Bacterium Virgibacillus dokdonensis 81:137 Molecular Characterization and Biocompatibility of Exopolysaccharide Produced by Moderately Halophilic Bacterium Virgibacillus dokdonensis from the Saltern of Kumta Coast. 36235941 14 69 theme EPS 2102:2104 arg1 biocompatibility 2075:2090 the significant biocompatibility 2059:2090 the significant biocompatibility of VITP14 EPS for synthesizing a variety of biomaterials 2059:2147 Our research unveils the significant biocompatibility of VITP14 EPS for synthesizing a variety of biomaterials. 36235941 11 70 theme -β-D-Glcp- 1471:1480 arg1 [α-D-Xylp- 1437:1446 1)[α-D-Xylp- 1435:1446 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4) 1433:1522 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 70 theme -β-D-Glcp- 1471:1480 arg1 -α-D-Glcp- 1454:1463 1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5) 1448:1487 1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5) 1448:1487 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 70 theme -β-D-Glcp- 1471:1480 arg1 → 1467:1467 1 → 6 1465:1469 1 → 6 1465:1469 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 70 theme -β-D-Glcp- 1471:1480 arg1 → 1484:1484 1 → 5 1482:1486 1 → 5 1482:1486 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 0 71 theme Virgibacillus 113:125 arg1 dokdonensis 127:137 Moderately Halophilic Bacterium Virgibacillus dokdonensis 81:137 Moderately Halophilic Bacterium Virgibacillus dokdonensis 81:137 Molecular Characterization and Biocompatibility of Exopolysaccharide Produced by Moderately Halophilic Bacterium Virgibacillus dokdonensis from the Saltern of Kumta Coast. 36235941 13 72 from time 2011:2014 arg1 tests 2031:2035 APTT and PT tests 2019:2035 tests 2031:2035 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 10 73 theme average 1250:1256 arg1 weight 1268:1273 an average molecular weight 1247:1273 an average molecular weight of 555 kDa 1247:1284 The polymer has an average molecular weight of 555 kDa. 36235941 9 74 theme groups/bonds 1164:1175 arg1 presence 1141:1148 the presence 1137:1148 the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O) 1137:1228 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 12 75 dep semicrystalline 1658:1672 arg1 % 1679:1679 54.2% 1675:1679 54.2% 1675:1679 The EPS is thermally stable till 251.4 °C. X-ray diffraction analysis confirmed the semicrystalline (54.2%) nature of the EPS. 36235941 14 76 theme significant 2063:2073 arg1 biocompatibility 2075:2090 the significant biocompatibility 2059:2090 the significant biocompatibility of VITP14 EPS for synthesizing a variety of biomaterials 2059:2147 Our research unveils the significant biocompatibility of VITP14 EPS for synthesizing a variety of biomaterials. 36235941 13 77 theme > 1867:1867 arg1 hemocompatibility 1825:1841 hemocompatibility 1825:1841 hemocompatibility (erythrocyte protection > 87%) 1825:1872 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 13 77 theme > 1867:1867 arg1 % 1871:1871 erythrocyte protection > 87% 1844:1871 erythrocyte protection > 87% 1844:1871 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 11 78 theme -β-D-Fruf- 1541:1550 arg1 -β-D-Ribp- 1558:1567 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp- 1433:1567 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp- 1433:1567 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 4 79 theme permeation 572:581 arg1 methods 599:605 gel permeation chromatographic methods 568:605 gel permeation chromatographic methods 568:605 The EPS was purified using ion exchange and gel permeation chromatographic methods. 36235941 5 80 theme web-like 619:626 arg1 structure 628:636 porous web-like structure 612:636 porous web-like structure 612:636 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 13 81 theme RAW264.7 1922:1929 arg1 cells 1954:1958 RAW264.7 and keratinocyte HaCaT cells 1922:1958 cells 1954:1958 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 2 82 dep structure 364:372 arg1 the 360:362 the 360:362 the 360:362 In this direction, the present study aims to explore the structure and biocompatibility of the EPS produced by Virgibacillus dokdonensis VITP14. 36235941 0 83 theme Exopolysaccharide 51:67 arg1 Biocompatibility 31:46 Biocompatibility 31:46 Biocompatibility 31:46 Molecular Characterization and Biocompatibility of Exopolysaccharide Produced by Moderately Halophilic Bacterium Virgibacillus dokdonensis from the Saltern of Kumta Coast. 36235941 0 83 theme Exopolysaccharide 51:67 arg1 Characterization 10:25 Molecular Characterization 0:25 Molecular Characterization 0:25 Molecular Characterization and Biocompatibility of Exopolysaccharide Produced by Moderately Halophilic Bacterium Virgibacillus dokdonensis from the Saltern of Kumta Coast. 36235941 13 84 theme cell 1898:1901 arg1 % 1917:1917 cell viability > 80% 1898:1917 cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells 1898:1958 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 3 85 theme marine 457:462 arg1 bacterium 464:472 This marine bacterium 452:472 This marine bacterium 452:472 This marine bacterium produces 17.3 g/L of EPS at 96 h of fermentation. 36235941 4 86 theme ion 551:553 arg1 exchange 555:562 ion exchange 551:562 ion exchange 551:562 The EPS was purified using ion exchange and gel permeation chromatographic methods. 36235941 11 87 theme → 1450:1450 arg1 [α-D-Xylp- 1437:1446 1)[α-D-Xylp- 1435:1446 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4) 1433:1522 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 87 theme → 1450:1450 arg1 -α-D-Glcp- 1454:1463 1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5) 1448:1487 1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5) 1448:1487 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 87 theme → 1450:1450 arg1 → 1467:1467 1 → 6 1465:1469 1 → 6 1465:1469 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 87 theme → 1450:1450 arg1 → 1484:1484 1 → 5 1482:1486 1 → 5 1482:1486 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 88 theme linkages 1388:1395 arg1 composition 1330:1340 the monomer composition 1318:1340 the monomer composition 1318:1340 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 88 theme linkages 1388:1395 arg1 existence 1347:1355 the existence 1343:1355 the existence of two α- and six β-glycosidic linkages 1343:1395 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 88 theme linkages 1388:1395 arg1 unit 1425:1428 the branched repeating unit 1402:1428 the branched repeating unit 1402:1428 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 3 89 theme EPS 495:497 arg1 g/L 488:490 17.3 g/L 483:490 17.3 g/L of EPS 483:497 This marine bacterium produces 17.3 g/L of EPS at 96 h of fermentation. 36235941 11 90 dep [α-D-Xylp- 1437:1446 arg1 1 1435:1435 1 1435:1435 1 1435:1435 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 13 91 theme > 1913:1913 arg1 % 1917:1917 cell viability > 80% 1898:1917 cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells 1898:1958 Further, the EPS exhibits significant water solubility (76.5%), water-holding capacity (266.8%), emulsifying index (66.8%), hemocompatibility (erythrocyte protection > 87%), and cytocompatibility (cell viability > 80% on RAW264.7 and keratinocyte HaCaT cells) at higher concentrations and prolongs coagulation time in APTT and PT tests. 36235941 9 92 theme EPSs 1188:1191 arg1 typical 1177:1183 typical 1177:1183 typical 1177:1183 The FTIR spectrum indicates the presence of functional groups/bonds typical of EPSs (O-H, C-H, C-O-H, C-O, S=O, and P=O). 36235941 5 93 theme EPS 692:694 arg1 structure 628:636 porous web-like structure 612:636 porous web-like structure 612:636 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 5 93 theme EPS 692:694 arg1 composition 652:662 elemental composition 642:662 elemental composition 642:662 The porous web-like structure and elemental composition (C, O, Na, Mg, P, S) of the EPS were inferred from SEM and EDX analysis. 36235941 7 94 theme anionic 863:869 arg1 nature 871:876 the anionic nature 859:876 the anionic nature of the EPS 859:887 The zeta potential value of −10 mV indicates the anionic nature of the EPS. 36235941 11 95 theme branched 1406:1413 arg1 unit 1425:1428 the branched repeating unit 1402:1428 the branched repeating unit 1402:1428 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 12 96 theme °C. 1613:1615 arg1 analysis 1635:1642 till 251.4 °C. X-ray diffraction analysis 1602:1642 till 251.4 °C. X-ray diffraction analysis 1602:1642 The EPS is thermally stable till 251.4 °C. X-ray diffraction analysis confirmed the semicrystalline (54.2%) nature of the EPS. 36235941 1 97 theme tissue 248:253 arg1 engineering 255:265 tissue engineering 248:265 tissue engineering due to their inherent biocompatibility 248:304 The use of natural polysaccharides as biomaterials is gaining importance in tissue engineering due to their inherent biocompatibility. 36235941 8 98 theme Initial 890:896 arg1 characterization 908:923 Initial molecular characterization 890:923 Initial molecular characterization 890:923 Initial molecular characterization showed that the EPS is a heteropolysaccharide composed of glucose (25.8%), ribose (18.6%), fructose (31.5%), and xylose (24%), which are the monosaccharide units in the HPLC analysis. 36235941 2 99 theme Virgibacillus 418:430 arg1 VITP14 444:449 Virgibacillus dokdonensis VITP14 418:449 Virgibacillus dokdonensis VITP14 418:449 In this direction, the present study aims to explore the structure and biocompatibility of the EPS produced by Virgibacillus dokdonensis VITP14. 36235941 11 100 theme → 1433:1433 arg1 -β-D-Frup- 1489:1498 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup- 1433:1498 → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4) 1433:1522 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 11 100 theme → 1433:1433 arg1 [β-D-Xylp- 1506:1515 2 → 2)[β-D-Xylp-(1 → 4 1500:1521 2 → 2)[β-D-Xylp-(1 → 4 1500:1521 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 36235941 2 101 dep Virgibacillus 418:430 arg1 dokdonensis 432:442 dokdonensis 432:442 dokdonensis 432:442 In this direction, the present study aims to explore the structure and biocompatibility of the EPS produced by Virgibacillus dokdonensis VITP14. 36235941 11 102 dep -α-D-Glcp- 1454:1463 arg1 2 1452:1452 2 1452:1452 2 1452:1452 Further, NMR analysis revealed the monomer composition, the existence of two α- and six β-glycosidic linkages, and the branched repeating unit as → 1)[α-D-Xylp-(1 → 2)-α-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 5)]-β-D-Frup-(2 → 2)[β-D-Xylp-(1 → 4)]-β-D-Xylp-(1 → 6)-β-D-Fruf-(2 → 4)-β-D-Ribp-(1 →. 35738989 6 0 theme polymicrobial 936:948 arg1 biofilm 950:956 the polymicrobial biofilm 932:956 the polymicrobial biofilm 932:956 RESULTS Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. 35738989 10 1 theme catheter 1421:1428 arg1 model 1430:1434 a catheter model 1419:1434 a catheter model 1419:1434 It seems that C. albicans contributes the most to the adhesion process and to the general structure of the biofilms on all the surfaces tested, including a catheter model. 35738989 8 2 theme polystyrene 1113:1123 arg1 wells 1125:1129 polystyrene wells 1113:1129 polystyrene wells 1113:1129 FBS decreased the adhesion to polystyrene wells for both microorganisms. 35738989 3 3 theme synergy 519:525 arg1 terms 491:495 terms 491:495 terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents 491:607 AIMS To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. 35738989 0 4 theme different 88:96 arg1 surfaces 98:105 different surfaces 88:105 different surfaces 88:105 Characterization of Candida albicans and Staphylococcus aureus polymicrobial biofilm on different surfaces. 35738989 14 5 theme polymicrobial 1843:1855 arg1 infections 1857:1866 polymicrobial infections 1843:1866 polymicrobial infections 1843:1866 Detection of polymicrobial infections and characterization of biofilms will be necessary in the future to provide a better treatment. 35738989 6 6 theme fetal 858:862 arg1 FBS 878:880 FBS 878:880 FBS 878:880 RESULTS Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. 35738989 6 6 theme fetal 858:862 arg1 serum 871:875 fetal bovine serum 858:875 fetal bovine serum (FBS) 858:881 RESULTS Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. 35738989 1 7 theme biofilm-associated 189:206 arg1 diseases 208:215 biofilm-associated diseases 189:215 biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections 189:284 BACKGROUND Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. 35738989 1 7 theme biofilm-associated 189:206 arg1 infections 275:284 burn wound infections 264:284 burn wound infections 264:284 BACKGROUND Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. 35738989 1 7 theme biofilm-associated 189:206 arg1 periodontitis 245:257 periodontitis 245:257 periodontitis 245:257 BACKGROUND Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. 35738989 1 7 theme biofilm-associated 189:206 arg1 stomatitis 233:242 denture stomatitis 225:242 denture stomatitis 225:242 BACKGROUND Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. 35738989 11 8 theme great 1471:1475 arg1 capacity 1486:1493 a great adhesion capacity 1469:1493 a great adhesion capacity to the surface of C. albicans 1469:1523 Interestingly, S. aureus showed a great adhesion capacity to the surface of C. albicans in the biofilms. 35738989 9 9 theme albicans 1227:1234 arg1 growth 1214:1219 the growth 1210:1219 the growth of C. albicans and S. aureus, respectively 1210:1262 Supplementing the media with glucose and FBS enhanced the growth of C. albicans and S. aureus, respectively. 35738989 0 10 from Characterization 0:15 arg1 surfaces 98:105 different surfaces 88:105 different surfaces 88:105 Characterization of Candida albicans and Staphylococcus aureus polymicrobial biofilm on different surfaces. 35738989 5 11 theme Scanning 682:689 arg1 microscopy 700:709 Scanning electron microscopy 682:709 Scanning electron microscopy 682:709 Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively. 35738989 10 12 theme biofilms 1372:1379 arg1 structure 1355:1363 the general structure 1343:1363 the general structure of the biofilms on all the surfaces tested, including a catheter model 1343:1434 It seems that C. albicans contributes the most to the adhesion process and to the general structure of the biofilms on all the surfaces tested, including a catheter model. 35738989 11 13 theme adhesion 1477:1484 arg1 capacity 1486:1493 a great adhesion capacity 1469:1493 a great adhesion capacity to the surface of C. albicans 1469:1523 Interestingly, S. aureus showed a great adhesion capacity to the surface of C. albicans in the biofilms. 35738989 4 14 theme Crystal 618:624 arg1 assay 633:637 METHODS Crystal violet assay 610:637 METHODS Crystal violet assay 610:637 METHODS Crystal violet assay was used to measure the biofilm formation. 35738989 12 15 from molecules 1614:1622 arg1 biofilm 1645:1651 the polymicrobial biofilm 1627:1651 the polymicrobial biofilm 1627:1651 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 6 16 theme aureus 921:926 arg1 formation 905:913 the biofilm formation 893:913 the biofilm formation of S. aureus 893:926 RESULTS Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. 35738989 6 16 theme aureus 921:926 arg1 biofilm 950:956 the polymicrobial biofilm 932:956 the polymicrobial biofilm 932:956 RESULTS Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. 35738989 5 17 theme electron 691:698 arg1 microscopy 700:709 Scanning electron microscopy 682:709 Scanning electron microscopy 682:709 Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively. 35738989 3 18 theme stability 556:564 arg1 terms 491:495 terms 491:495 terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents 491:607 AIMS To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. 35738989 7 19 contain had 1039:1041 arg2 effect 1054:1059 a positive effect 1043:1059 a positive effect 1043:1059 For C. albicans, depending on the culture media, the addition of glucose or FBS had a positive effect in biofilm formation. 35738989 7 19 contain had 1039:1041 arg1 addition 1012:1019 the addition 1008:1019 the addition of glucose or FBS 1008:1037 For C. albicans, depending on the culture media, the addition of glucose or FBS had a positive effect in biofilm formation. 35738989 4 20 theme METHODS 610:616 arg1 assay 633:637 METHODS Crystal violet assay 610:637 METHODS Crystal violet assay 610:637 METHODS Crystal violet assay was used to measure the biofilm formation. 35738989 3 21 theme density 510:516 arg1 terms 491:495 terms 491:495 terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents 491:607 AIMS To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. 35738989 14 22 from future 1926:1931 arg1 necessary 1909:1917 necessary 1909:1917 necessary 1909:1917 Detection of polymicrobial infections and characterization of biofilms will be necessary in the future to provide a better treatment. 35738989 3 23 theme structure 541:549 arg1 terms 491:495 terms 491:495 terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents 491:607 AIMS To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. 35738989 13 24 theme fungus 1822:1827 arg1 form 1810:1813 the hyphal form 1799:1813 the hyphal form of the fungus 1799:1827 CONCLUSIONS The polymicrobial biofilm had a complex structure, with C. albicans serving as a scaffold where S. aureus adheres, preferentially to the hyphal form of the fungus. 35738989 3 25 theme albicans 465:472 arg1 biofilm 451:457 the polymicrobial biofilm 433:457 the polymicrobial biofilm of C. albicans and S. aureus 433:486 AIMS To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. 35738989 5 26 theme chemical 774:781 arg1 composition 783:793 chemical composition 774:793 chemical composition 774:793 Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively. 35738989 13 27 theme complex 1698:1704 arg1 structure 1706:1714 a complex structure 1696:1714 a complex structure 1696:1714 CONCLUSIONS The polymicrobial biofilm had a complex structure, with C. albicans serving as a scaffold where S. aureus adheres, preferentially to the hyphal form of the fungus. 35738989 3 28 theme polymicrobial 437:449 arg1 biofilm 451:457 the polymicrobial biofilm 433:457 the polymicrobial biofilm of C. albicans and S. aureus 433:486 AIMS To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. 35738989 4 29 theme violet 626:631 arg1 assay 633:637 METHODS Crystal violet assay 610:637 METHODS Crystal violet assay 610:637 METHODS Crystal violet assay was used to measure the biofilm formation. 35738989 14 30 theme biofilms 1892:1899 arg1 characterization 1872:1887 characterization 1872:1887 characterization of biofilms 1872:1899 Detection of polymicrobial infections and characterization of biofilms will be necessary in the future to provide a better treatment. 35738989 14 30 theme biofilms 1892:1899 arg1 Detection 1830:1838 Detection 1830:1838 Detection of polymicrobial infections 1830:1866 Detection of polymicrobial infections and characterization of biofilms will be necessary in the future to provide a better treatment. 35738989 14 31 theme better 1946:1951 arg1 treatment 1953:1961 a better treatment 1944:1961 a better treatment 1944:1961 Detection of polymicrobial infections and characterization of biofilms will be necessary in the future to provide a better treatment. 35738989 5 32 theme biofilms 802:809 arg1 structure 760:768 structure 760:768 structure 760:768 Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively. 35738989 5 32 theme biofilms 802:809 arg1 composition 783:793 chemical composition 774:793 chemical composition 774:793 Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively. 35738989 2 33 theme polymicrobial 333:345 arg1 biofilm 347:353 the polymicrobial biofilm 329:353 the polymicrobial biofilm of both microorganisms 329:376 However, the polymicrobial biofilm of both microorganisms has not been fully characterized. 35738989 12 34 theme polymicrobial 1631:1643 arg1 biofilm 1645:1651 the polymicrobial biofilm 1627:1651 the polymicrobial biofilm 1627:1651 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 13 35 theme polymicrobial 1670:1682 arg1 biofilm 1684:1690 The polymicrobial biofilm 1666:1690 The polymicrobial biofilm 1666:1690 CONCLUSIONS The polymicrobial biofilm had a complex structure, with C. albicans serving as a scaffold where S. aureus adheres, preferentially to the hyphal form of the fungus. 35738989 11 36 theme albicans 1516:1523 arg1 surface 1502:1508 the surface 1498:1508 the surface of C. albicans 1498:1523 Interestingly, S. aureus showed a great adhesion capacity to the surface of C. albicans in the biofilms. 35738989 3 37 theme chemical 593:600 arg1 agents 602:607 chemical agents 593:607 chemical agents 593:607 AIMS To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. 35738989 6 38 dep media 847:851 arg1 decreased 883:891 decreased 883:891 decreased the biofilm formation of S. aureus and the polymicrobial biofilm 883:956 RESULTS Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. 35738989 1 39 theme denture 225:231 arg1 stomatitis 233:242 denture stomatitis 225:242 denture stomatitis 225:242 BACKGROUND Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. 35738989 0 40 theme albicans 28:35 arg1 Characterization 0:15 Characterization 0:15 Characterization of Candida albicans 0:35 Characterization of Candida albicans and Staphylococcus aureus polymicrobial biofilm on different surfaces. 35738989 0 40 theme albicans 28:35 arg1 biofilm 77:83 Staphylococcus aureus polymicrobial biofilm 41:83 Staphylococcus aureus polymicrobial biofilm 41:83 Characterization of Candida albicans and Staphylococcus aureus polymicrobial biofilm on different surfaces. 35738989 1 41 theme medical 303:309 arg1 devices 311:317 medical devices 303:317 medical devices 303:317 BACKGROUND Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. 35738989 7 42 theme biofilm 1064:1070 arg1 formation 1072:1080 biofilm formation 1064:1080 biofilm formation 1064:1080 For C. albicans, depending on the culture media, the addition of glucose or FBS had a positive effect in biofilm formation. 35738989 13 43 theme hyphal 1803:1808 arg1 form 1810:1813 the hyphal form 1799:1813 the hyphal form of the fungus 1799:1827 CONCLUSIONS The polymicrobial biofilm had a complex structure, with C. albicans serving as a scaffold where S. aureus adheres, preferentially to the hyphal form of the fungus. 35738989 0 44 theme Candida 20:26 arg1 albicans 28:35 Candida albicans 20:35 Candida albicans 20:35 Characterization of Candida albicans and Staphylococcus aureus polymicrobial biofilm on different surfaces. 35738989 4 45 used used 643:646 arg2 assay 633:637 METHODS Crystal violet assay 610:637 METHODS Crystal violet assay 610:637 METHODS Crystal violet assay was used to measure the biofilm formation. 35738989 6 46 theme biofilm 897:903 arg1 formation 905:913 the biofilm formation 893:913 the biofilm formation of S. aureus 893:926 RESULTS Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. 35738989 10 47 from surfaces 1392:1399 arg1 structure 1355:1363 the general structure 1343:1363 the general structure of the biofilms on all the surfaces tested, including a catheter model 1343:1434 It seems that C. albicans contributes the most to the adhesion process and to the general structure of the biofilms on all the surfaces tested, including a catheter model. 35738989 14 48 theme infections 1857:1866 arg1 characterization 1872:1887 characterization 1872:1887 characterization of biofilms 1872:1899 Detection of polymicrobial infections and characterization of biofilms will be necessary in the future to provide a better treatment. 35738989 14 48 theme infections 1857:1866 arg1 Detection 1830:1838 Detection 1830:1838 Detection of polymicrobial infections 1830:1866 Detection of polymicrobial infections and characterization of biofilms will be necessary in the future to provide a better treatment. 35738989 0 49 theme Staphylococcus 41:54 arg1 biofilm 77:83 Staphylococcus aureus polymicrobial biofilm 41:83 Staphylococcus aureus polymicrobial biofilm 41:83 Characterization of Candida albicans and Staphylococcus aureus polymicrobial biofilm on different surfaces. 35738989 10 50 from structure 1355:1363 arg1 surfaces 1392:1399 all the surfaces 1384:1399 all the surfaces tested 1384:1406 It seems that C. albicans contributes the most to the adhesion process and to the general structure of the biofilms on all the surfaces tested, including a catheter model. 35738989 12 51 theme important 1604:1612 arg1 molecules 1614:1622 the most important molecules 1595:1622 the most important molecules in the polymicrobial biofilm 1595:1651 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 12 51 theme important 1604:1612 arg1 Proteins 1542:1549 Proteins 1542:1549 Proteins 1542:1549 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 12 51 theme important 1604:1612 arg1 polysaccharides 1568:1582 β-1,6-linked polysaccharides 1555:1582 β-1,6-linked polysaccharides 1555:1582 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 4 52 theme biofilm 663:669 arg1 formation 671:679 the biofilm formation 659:679 the biofilm formation 659:679 METHODS Crystal violet assay was used to measure the biofilm formation. 35738989 10 53 from biofilms 1372:1379 arg1 surfaces 1392:1399 all the surfaces 1384:1399 all the surfaces tested 1384:1406 It seems that C. albicans contributes the most to the adhesion process and to the general structure of the biofilms on all the surfaces tested, including a catheter model. 35738989 7 54 theme glucose 1024:1030 arg1 addition 1012:1019 the addition 1008:1019 the addition of glucose or FBS 1008:1037 For C. albicans, depending on the culture media, the addition of glucose or FBS had a positive effect in biofilm formation. 35738989 3 55 theme aureus 481:486 arg1 biofilm 451:457 the polymicrobial biofilm 433:457 the polymicrobial biofilm of C. albicans and S. aureus 433:486 AIMS To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. 35738989 0 56 theme polymicrobial 63:75 arg1 biofilm 77:83 Staphylococcus aureus polymicrobial biofilm 41:83 Staphylococcus aureus polymicrobial biofilm 41:83 Characterization of Candida albicans and Staphylococcus aureus polymicrobial biofilm on different surfaces. 35738989 0 57 from biofilm 77:83 arg1 surfaces 98:105 different surfaces 88:105 different surfaces 88:105 Characterization of Candida albicans and Staphylococcus aureus polymicrobial biofilm on different surfaces. 35738989 0 58 dep Staphylococcus 41:54 arg1 aureus 56:61 aureus 56:61 aureus 56:61 Characterization of Candida albicans and Staphylococcus aureus polymicrobial biofilm on different surfaces. 35738989 7 59 theme FBS 1035:1037 arg1 addition 1012:1019 the addition 1008:1019 the addition of glucose or FBS 1008:1037 For C. albicans, depending on the culture media, the addition of glucose or FBS had a positive effect in biofilm formation. 35738989 2 60 theme microorganisms 363:376 arg1 biofilm 347:353 the polymicrobial biofilm 329:353 the polymicrobial biofilm of both microorganisms 329:376 However, the polymicrobial biofilm of both microorganisms has not been fully characterized. 35738989 13 61 theme C. 1722:1723 arg1 albicans 1725:1732 C. albicans 1722:1732 C. albicans serving as a scaffold where S. aureus adheres, preferentially to the hyphal form of the fungus 1722:1827 CONCLUSIONS The polymicrobial biofilm had a complex structure, with C. albicans serving as a scaffold where S. aureus adheres, preferentially to the hyphal form of the fungus. 35738989 12 62 theme β-1,6-linked 1555:1566 arg1 molecules 1614:1622 the most important molecules 1595:1622 the most important molecules in the polymicrobial biofilm 1595:1651 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 12 62 theme β-1,6-linked 1555:1566 arg1 Proteins 1542:1549 Proteins 1542:1549 Proteins 1542:1549 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 12 62 theme β-1,6-linked 1555:1566 arg1 polysaccharides 1568:1582 β-1,6-linked polysaccharides 1555:1582 β-1,6-linked polysaccharides 1555:1582 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 7 63 theme positive 1045:1052 arg1 effect 1054:1059 a positive effect 1043:1059 a positive effect 1043:1059 For C. albicans, depending on the culture media, the addition of glucose or FBS had a positive effect in biofilm formation. 35738989 9 64 theme aureus 1243:1248 arg1 growth 1214:1219 the growth 1210:1219 the growth of C. albicans and S. aureus, respectively 1210:1262 Supplementing the media with glucose and FBS enhanced the growth of C. albicans and S. aureus, respectively. 35738989 10 65 theme adhesion 1319:1326 arg1 process 1328:1334 the adhesion process 1315:1334 the adhesion process 1315:1334 It seems that C. albicans contributes the most to the adhesion process and to the general structure of the biofilms on all the surfaces tested, including a catheter model. 35738989 1 66 theme Candida 145:151 arg1 albicans 153:160 Candida albicans 145:160 Candida albicans 145:160 BACKGROUND Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. 35738989 5 67 theme confocal 715:722 arg1 microscopy 724:733 confocal microscopy 715:733 confocal microscopy 715:733 Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively. 35738989 12 68 link β-1,6-linked 1555:1566 arg1 molecules 1614:1622 the most important molecules 1595:1622 the most important molecules in the polymicrobial biofilm 1595:1651 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 12 68 link β-1,6-linked 1555:1566 arg1 Proteins 1542:1549 Proteins 1542:1549 Proteins 1542:1549 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 12 68 link β-1,6-linked 1555:1566 arg1 polysaccharides 1568:1582 β-1,6-linked polysaccharides 1555:1582 β-1,6-linked polysaccharides 1555:1582 Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. 35738989 11 69 theme C. 1513:1514 arg1 albicans 1516:1523 C. albicans 1513:1523 C. albicans 1513:1523 Interestingly, S. aureus showed a great adhesion capacity to the surface of C. albicans in the biofilms. 35738989 13 70 contain had 1692:1694 arg2 structure 1706:1714 a complex structure 1696:1714 a complex structure 1696:1714 CONCLUSIONS The polymicrobial biofilm had a complex structure, with C. albicans serving as a scaffold where S. aureus adheres, preferentially to the hyphal form of the fungus. 35738989 13 70 contain had 1692:1694 arg1 biofilm 1684:1690 The polymicrobial biofilm 1666:1690 The polymicrobial biofilm 1666:1690 CONCLUSIONS The polymicrobial biofilm had a complex structure, with C. albicans serving as a scaffold where S. aureus adheres, preferentially to the hyphal form of the fungus. 35738989 9 71 with media 1174:1178 arg1 FBS 1197:1199 FBS 1197:1199 FBS 1197:1199 Supplementing the media with glucose and FBS enhanced the growth of C. albicans and S. aureus, respectively. 35738989 9 71 with media 1174:1178 arg1 glucose 1185:1191 glucose 1185:1191 glucose 1185:1191 Supplementing the media with glucose and FBS enhanced the growth of C. albicans and S. aureus, respectively. 35738989 5 72 dep structure 760:768 arg1 the 756:758 the 756:758 the 756:758 Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively. 35738989 14 73 from necessary 1909:1917 arg1 future 1926:1931 future 1926:1931 future 1926:1931 Detection of polymicrobial infections and characterization of biofilms will be necessary in the future to provide a better treatment. 35738989 9 74 theme Supplementing 1156:1168 arg1 media 1174:1178 the media 1170:1178 Supplementing the media with glucose and FBS 1156:1199 Supplementing the media with glucose and FBS enhanced the growth of C. albicans and S. aureus, respectively. 35738989 3 75 theme microbial 500:508 arg1 density 510:516 microbial density 500:516 microbial density 500:516 AIMS To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. 35738989 1 76 theme burn 264:267 arg1 infections 275:284 burn wound infections 264:284 burn wound infections 264:284 BACKGROUND Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. 35738989 6 77 theme bovine 864:869 arg1 FBS 878:880 FBS 878:880 FBS 878:880 RESULTS Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. 35738989 6 77 theme bovine 864:869 arg1 serum 871:875 fetal bovine serum 858:875 fetal bovine serum (FBS) 858:881 RESULTS Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. 35738989 10 78 theme general 1347:1353 arg1 structure 1355:1363 the general structure 1343:1363 the general structure of the biofilms on all the surfaces tested, including a catheter model 1343:1434 It seems that C. albicans contributes the most to the adhesion process and to the general structure of the biofilms on all the surfaces tested, including a catheter model. 35738989 3 79 theme composition 528:538 arg1 terms 491:495 terms 491:495 terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents 491:607 AIMS To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. 35738989 1 80 theme wound 269:273 arg1 infections 275:284 burn wound infections 264:284 burn wound infections 264:284 BACKGROUND Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. 35738989 5 81 used used 740:743 arg2 microscopy 700:709 Scanning electron microscopy 682:709 Scanning electron microscopy 682:709 Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively. 35738989 5 81 used used 740:743 arg2 microscopy 724:733 confocal microscopy 715:733 confocal microscopy 715:733 Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively. 35738989 7 82 theme culture 993:999 arg1 media 1001:1005 the culture media 989:1005 the culture media 989:1005 For C. albicans, depending on the culture media, the addition of glucose or FBS had a positive effect in biofilm formation. 35738989 13 83 dep CONCLUSIONS 1654:1664 arg1 had 1692:1694 had 1692:1694 had 1692:1694 CONCLUSIONS The polymicrobial biofilm had a complex structure, with C. albicans serving as a scaffold where S. aureus adheres, preferentially to the hyphal form of the fungus. 37146167 0 0 theme Dissociation 105:116 arg1 Spectrometry 138:149 Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 64:149 Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 64:149 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 37146167 2 1 theme mobile 526:531 arg1 phases 533:538 the mobile phases 522:538 the mobile phases 522:538 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 4 2 theme capture 759:765 arg1 dissociation 767:778 hot electron capture dissociation 746:778 hot electron capture dissociation using an electron beam energy higher than 5 eV 746:825 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 1 3 link N-linked 309:316 arg1 glycans 318:324 N-linked glycans 309:324 N-linked glycans 309:324 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 1 4 theme liquid 178:183 arg1 chromatography 185:198 a novel liquid chromatography 170:198 a novel liquid chromatography coupled with tandem mass spectrometry method 170:243 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 6 5 theme Sa-Gal 1172:1177 arg1 products 1179:1186 the Sa-Gal products 1168:1186 the Sa-Gal products 1168:1186 We proposed a rule to characterize the Sa linkages using the Sa-Gal products. 37146167 0 6 theme Chromatography-Electron-Activated 71:103 arg1 Spectrometry 138:149 Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 64:149 Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 64:149 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 37146167 8 7 from glycoforms 1352:1361 arg1 glycopeptides 1370:1382 the glycopeptides 1366:1382 the glycopeptides with different Sa links 1366:1406 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 8 8 from number 1333:1338 arg1 glycopeptides 1370:1382 the glycopeptides 1366:1382 the glycopeptides with different Sa links 1366:1406 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 4 9 theme electron 750:757 arg1 dissociation 767:778 hot electron capture dissociation 746:778 hot electron capture dissociation using an electron beam energy higher than 5 eV 746:825 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 8 10 theme Sa 1399:1400 arg1 links 1402:1406 different Sa links 1389:1406 different Sa links 1389:1406 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 0 11 theme Mass 133:136 arg1 Spectrometry 138:149 Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 64:149 Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 64:149 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 37146167 0 12 from Analysis 0:7 arg1 Glycopeptides 44:56 N-Linked Glycopeptides 35:56 N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 35:149 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 37146167 5 13 theme Sa 1055:1056 arg1 linkages 1058:1065 Sa linkages 1055:1065 Sa linkages 1055:1065 Such glycosidic bond cleavage at the reducing end (C-type ion) showed the difference in Sa linkages between Sa-Gal, Gal-GlcNAc, and GlcNAc-Man. 37146167 5 14 theme reducing 1004:1011 arg1 end 1013:1015 the reducing end 1000:1015 the reducing end (C-type ion) 1000:1028 Such glycosidic bond cleavage at the reducing end (C-type ion) showed the difference in Sa linkages between Sa-Gal, Gal-GlcNAc, and GlcNAc-Man. 37146167 5 14 theme reducing 1004:1011 arg1 ion 1025:1027 C-type ion 1018:1027 C-type ion 1018:1027 Such glycosidic bond cleavage at the reducing end (C-type ion) showed the difference in Sa linkages between Sa-Gal, Gal-GlcNAc, and GlcNAc-Man. 37146167 4 15 from bonds 846:850 arg1 glycopeptides 855:867 glycopeptides 855:867 glycopeptides 855:867 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 3 16 gly N-glycopeptides 677:691 arg2 N-glycopeptides 677:691 N-glycopeptides 677:691 N-glycopeptides using electron-activated dissociation 677:729 We also demonstrated a novel characterization method of Sa linkages in N-glycopeptides using electron-activated dissociation. 37146167 0 17 theme Time-of-Flight 118:131 arg1 Spectrometry 138:149 Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 64:149 Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 64:149 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 37146167 1 18 with glycopeptides 329:341 arg1 derivatization 363:376 no sialic acid derivatization 348:376 no sialic acid derivatization 348:376 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 2 19 gly N-glycopeptides 561:575 arg2 N-glycopeptides 561:575 the N-glycopeptides 557:575 the N-glycopeptides depending on the Sa linkage 557:603 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 7 20 gly N-glycopeptides 1216:1230 arg2 N-glycopeptides 1216:1230 N-glycopeptides 1216:1230 N-glycopeptides 1216:1230 This method was applied to N-glycopeptides in tryptic fetuin digest separated by an optimized reversed-phase HPLC. 37146167 4 21 theme glycosidic 835:844 arg1 bonds 846:850 glycosidic bonds 835:850 glycosidic bonds in glycopeptides 835:867 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 5 22 theme Such 967:970 arg1 cleavage 988:995 Such glycosidic bond cleavage 967:995 Such glycosidic bond cleavage at the reducing end (C-type ion) 967:1028 Such glycosidic bond cleavage at the reducing end (C-type ion) showed the difference in Sa linkages between Sa-Gal, Gal-GlcNAc, and GlcNAc-Man. 37146167 2 23 theme high-performance 432:447 arg1 chromatography 456:469 reversed-phase high-performance liquid chromatography 417:469 reversed-phase high-performance liquid chromatography (HPLC) 417:476 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 2 23 theme high-performance 432:447 arg1 HPLC 472:475 HPLC 472:475 HPLC 472:475 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 2 24 theme formic 493:498 arg1 concentration 505:517 a higher formic acid concentration 484:517 a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage 484:603 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 8 25 gly glycoforms 1352:1361 arg2 glycopeptides 1370:1382 the glycopeptides 1366:1382 the glycopeptides with different Sa links 1366:1406 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 5 26 theme bond 983:986 arg1 cleavage 988:995 Such glycosidic bond cleavage 967:995 Such glycosidic bond cleavage at the reducing end (C-type ion) 967:1028 Such glycosidic bond cleavage at the reducing end (C-type ion) showed the difference in Sa linkages between Sa-Gal, Gal-GlcNAc, and GlcNAc-Man. 37146167 2 27 theme reversed-phase 417:430 arg1 chromatography 456:469 reversed-phase high-performance liquid chromatography 417:469 reversed-phase high-performance liquid chromatography (HPLC) 417:476 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 2 27 theme reversed-phase 417:430 arg1 HPLC 472:475 HPLC 472:475 HPLC 472:475 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 2 28 theme higher 486:491 arg1 concentration 505:517 a higher formic acid concentration 484:517 a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage 484:603 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 2 29 from concentration 505:517 arg1 phases 533:538 the mobile phases 522:538 the mobile phases 522:538 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 7 30 theme tryptic 1235:1241 arg1 digest 1250:1255 tryptic fetuin digest 1235:1255 tryptic fetuin digest separated by an optimized reversed-phase HPLC 1235:1301 This method was applied to N-glycopeptides in tryptic fetuin digest separated by an optimized reversed-phase HPLC. 37146167 7 31 theme fetuin 1243:1248 arg1 digest 1250:1255 tryptic fetuin digest 1235:1255 tryptic fetuin digest separated by an optimized reversed-phase HPLC 1235:1301 This method was applied to N-glycopeptides in tryptic fetuin digest separated by an optimized reversed-phase HPLC. 37146167 4 32 theme energy 803:808 arg1 eV 824:825 an electron beam energy higher than 5 eV 786:825 an electron beam energy higher than 5 eV 786:825 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 1 33 theme tandem 213:218 arg1 spectrometry 225:236 tandem mass spectrometry 213:236 tandem mass spectrometry method 213:243 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 4 34 theme beam 798:801 arg1 eV 824:825 an electron beam energy higher than 5 eV 786:825 an electron beam energy higher than 5 eV 786:825 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 8 35 theme different 1389:1397 arg1 links 1402:1406 different Sa links 1389:1406 different Sa links 1389:1406 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 1 36 theme mass 220:223 arg1 spectrometry 225:236 tandem mass spectrometry 213:236 tandem mass spectrometry method 213:243 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 0 37 theme Acid 19:22 arg1 Linkage 24:30 Sialic Acid Linkage 12:30 Sialic Acid Linkage 12:30 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 37146167 1 38 theme N-linked 309:316 arg1 glycans 318:324 N-linked glycans 309:324 N-linked glycans 309:324 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 2 39 theme Sa 594:595 arg1 linkage 597:603 the Sa linkage 590:603 the Sa linkage 590:603 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 1 40 theme spectrometry 225:236 arg1 method 238:243 tandem mass spectrometry method 213:243 tandem mass spectrometry method 213:243 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 0 41 theme Sialic 12:17 arg1 Linkage 24:30 Sialic Acid Linkage 12:30 Sialic Acid Linkage 12:30 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 37146167 1 42 from linkage 298:304 arg1 glycans 318:324 N-linked glycans 309:324 N-linked glycans 309:324 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 1 42 from linkage 298:304 arg1 glycopeptides 329:341 glycopeptides 329:341 glycopeptides with no sialic acid derivatization 329:376 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 8 43 theme peptide 1415:1421 arg1 backbones 1423:1431 backbones 1423:1431 backbones 1423:1431 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 8 44 theme glycoforms 1352:1361 arg1 number 1333:1338 a number 1331:1338 a number 1331:1338 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 5 45 from difference 1041:1050 arg1 linkages 1058:1065 Sa linkages 1055:1065 Sa linkages 1055:1065 Such glycosidic bond cleavage at the reducing end (C-type ion) showed the difference in Sa linkages between Sa-Gal, Gal-GlcNAc, and GlcNAc-Man. 37146167 8 46 theme isomeric 1343:1350 arg1 glycoforms 1352:1361 isomeric glycoforms 1343:1361 isomeric glycoforms in the glycopeptides with different Sa links 1343:1406 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 3 47 theme electron-activated 699:716 arg1 dissociation 718:729 electron-activated dissociation 699:729 electron-activated dissociation 699:729 We also demonstrated a novel characterization method of Sa linkages in N-glycopeptides using electron-activated dissociation. 37146167 3 48 theme novel 629:633 arg1 method 652:657 a novel characterization method 627:657 a novel characterization method of Sa linkages 627:672 We also demonstrated a novel characterization method of Sa linkages in N-glycopeptides using electron-activated dissociation. 37146167 0 49 theme Linkage 24:30 arg1 Analysis 0:7 Analysis 0:7 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 0:150 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 37146167 3 50 theme characterization 635:650 arg1 method 652:657 a novel characterization method 627:657 a novel characterization method of Sa linkages 627:672 We also demonstrated a novel characterization method of Sa linkages in N-glycopeptides using electron-activated dissociation. 37146167 8 51 from glycopeptides 1370:1382 arg1 number 1333:1338 a number 1331:1338 a number 1331:1338 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 2 52 theme liquid 449:454 arg1 chromatography 456:469 reversed-phase high-performance liquid chromatography 417:469 reversed-phase high-performance liquid chromatography (HPLC) 417:476 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 2 52 theme liquid 449:454 arg1 HPLC 472:475 HPLC 472:475 HPLC 472:475 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 2 53 theme acid 500:503 arg1 concentration 505:517 a higher formic acid concentration 484:517 a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage 484:603 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 1 54 dep acid 280:283 arg1 Sa 294:295 Sa 294:295 Sa 294:295 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 1 54 dep acid 280:283 arg1 Neu5Ac 286:291 Neu5Ac 286:291 Neu5Ac 286:291 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 4 55 theme glycosidic 888:897 arg1 bond 899:902 each glycosidic bond 883:902 each glycosidic bond in the antennas 883:918 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 2 56 from separation 403:412 arg1 chromatography 456:469 reversed-phase high-performance liquid chromatography 417:469 reversed-phase high-performance liquid chromatography (HPLC) 417:476 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 2 56 from separation 403:412 arg1 HPLC 472:475 HPLC 472:475 HPLC 472:475 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 6 57 theme Sa 1150:1151 arg1 linkages 1153:1160 the Sa linkages 1146:1160 the Sa linkages using the Sa-Gal products 1146:1186 We proposed a rule to characterize the Sa linkages using the Sa-Gal products. 37146167 0 58 theme N-Linked 35:42 arg1 Glycopeptides 44:56 N-Linked Glycopeptides 35:56 N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 35:149 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 37146167 4 59 from bond 899:902 arg1 antennas 911:918 the antennas 907:918 the antennas 907:918 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 8 60 gly glycopeptides 1370:1382 arg2 glycopeptides 1370:1382 the glycopeptides 1366:1382 the glycopeptides with different Sa links 1366:1406 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 1 61 theme sialic 351:356 arg1 derivatization 363:376 no sialic acid derivatization 348:376 no sialic acid derivatization 348:376 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 4 62 theme oxygen 954:959 arg1 atom 961:964 the oxygen atom 950:964 the oxygen atom 950:964 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 3 63 theme Sa 662:663 arg1 linkages 665:672 Sa linkages 662:672 Sa linkages 662:672 We also demonstrated a novel characterization method of Sa linkages in N-glycopeptides using electron-activated dissociation. 37146167 7 64 theme optimized 1273:1281 arg1 HPLC 1298:1301 an optimized reversed-phase HPLC 1270:1301 an optimized reversed-phase HPLC 1270:1301 This method was applied to N-glycopeptides in tryptic fetuin digest separated by an optimized reversed-phase HPLC. 37146167 4 65 theme electron 789:796 arg1 eV 824:825 an electron beam energy higher than 5 eV 786:825 an electron beam energy higher than 5 eV 786:825 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 1 66 theme N-acetylneuraminic 261:278 arg1 acid 280:283 N-acetylneuraminic acid 261:283 N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization 261:376 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 5 67 theme C-type 1018:1023 arg1 end 1013:1015 the reducing end 1000:1015 the reducing end (C-type ion) 1000:1028 Such glycosidic bond cleavage at the reducing end (C-type ion) showed the difference in Sa linkages between Sa-Gal, Gal-GlcNAc, and GlcNAc-Man. 37146167 5 67 theme C-type 1018:1023 arg1 ion 1025:1027 C-type ion 1018:1027 C-type ion 1018:1027 Such glycosidic bond cleavage at the reducing end (C-type ion) showed the difference in Sa linkages between Sa-Gal, Gal-GlcNAc, and GlcNAc-Man. 37146167 2 68 from N-glycopeptides 561:575 arg1 linkage 597:603 the Sa linkage 590:603 the Sa linkage 590:603 First, we established a separation in reversed-phase high-performance liquid chromatography (HPLC) using a higher formic acid concentration in the mobile phases, which separated the N-glycopeptides depending on the Sa linkage. 37146167 3 69 theme linkages 665:672 arg1 method 652:657 a novel characterization method 627:657 a novel characterization method of Sa linkages 627:672 We also demonstrated a novel characterization method of Sa linkages in N-glycopeptides using electron-activated dissociation. 37146167 5 70 theme glycosidic 972:981 arg1 cleavage 988:995 Such glycosidic bond cleavage 967:995 Such glycosidic bond cleavage at the reducing end (C-type ion) 967:1028 Such glycosidic bond cleavage at the reducing end (C-type ion) showed the difference in Sa linkages between Sa-Gal, Gal-GlcNAc, and GlcNAc-Man. 37146167 4 71 theme atom 961:964 arg1 sides 941:945 both sides 936:945 both sides of the oxygen atom 936:964 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 1 72 theme acid 280:283 arg1 linkage 298:304 N-acetylneuraminic acid (Neu5Ac, Sa) linkage 261:304 N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization 261:376 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 0 73 theme Liquid 64:69 arg1 Spectrometry 138:149 Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 64:149 Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry 64:149 Analysis of Sialic Acid Linkage in N-Linked Glycopeptides Using Liquid Chromatography-Electron-Activated Dissociation Time-of-Flight Mass Spectrometry. 37146167 5 74 from end 1013:1015 arg1 cleavage 988:995 Such glycosidic bond cleavage 967:995 Such glycosidic bond cleavage at the reducing end (C-type ion) 967:1028 Such glycosidic bond cleavage at the reducing end (C-type ion) showed the difference in Sa linkages between Sa-Gal, Gal-GlcNAc, and GlcNAc-Man. 37146167 8 75 theme hot 1471:1473 arg1 ECD 1475:1477 hot ECD 1471:1477 hot ECD 1471:1477 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 1 76 gly glycopeptides 329:341 arg2 glycopeptides 329:341 glycopeptides 329:341 glycopeptides with no sialic acid derivatization 329:376 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 4 77 theme hot 746:748 arg1 dissociation 767:778 hot electron capture dissociation 746:778 hot electron capture dissociation using an electron beam energy higher than 5 eV 746:825 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 8 78 with glycopeptides 1370:1382 arg1 links 1402:1406 different Sa links 1389:1406 different Sa links 1389:1406 We successfully identified a number of isomeric glycoforms in the glycopeptides with different Sa links, whose peptide backbones were also simultaneously sequenced by hot ECD. 37146167 4 79 gly glycopeptides 855:867 arg2 glycopeptides 855:867 glycopeptides 855:867 glycopeptides 855:867 We found that hot electron capture dissociation using an electron beam energy higher than 5 eV cleaved glycosidic bonds in glycopeptides, resulting in each glycosidic bond in the antennas being broken on both sides of the oxygen atom. 37146167 1 80 theme acid 358:361 arg1 derivatization 363:376 no sialic acid derivatization 348:376 no sialic acid derivatization 348:376 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 37146167 7 81 theme reversed-phase 1283:1296 arg1 HPLC 1298:1301 an optimized reversed-phase HPLC 1270:1301 an optimized reversed-phase HPLC 1270:1301 This method was applied to N-glycopeptides in tryptic fetuin digest separated by an optimized reversed-phase HPLC. 37146167 1 82 theme novel 172:176 arg1 chromatography 185:198 a novel liquid chromatography 170:198 a novel liquid chromatography coupled with tandem mass spectrometry method 170:243 Herein, we report a novel liquid chromatography coupled with tandem mass spectrometry method to characterize N-acetylneuraminic acid (Neu5Ac, Sa) linkage in N-linked glycans in glycopeptides with no sialic acid derivatization. 34478135 0 0 from Production 22:31 arg1 ExpiCHO-S™ 36:45 ExpiCHO-S™ 36:45 ExpiCHO-S™ 36:45 Large-Scale Transient Production in ExpiCHO-S™ with Enhanced N-Galactosylation-Sialylation and PEI-Based Transfection. 34478135 2 1 theme glycoproteins 414:426 arg1 expression 388:397 transient expression 378:397 transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system 378:493 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 1 2 theme biotherapeutics 286:300 arg1 discovery 307:315 biotherapeutics drug discovery 286:315 biotherapeutics drug discovery 286:315 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 2 3 theme transient 378:386 arg1 expression 388:397 transient expression 378:397 transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system 378:493 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 2 4 theme therapeutic 402:412 arg1 glycoproteins 414:426 therapeutic glycoproteins 402:426 therapeutic glycoproteins with improved galactosylation and sialylation 402:472 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 1 5 theme drug 302:305 arg1 discovery 307:315 biotherapeutics drug discovery 286:315 biotherapeutics drug discovery 286:315 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 3 6 from transfection 579:590 arg1 cells 606:610 ExpiCHO-S™ cells 595:610 ExpiCHO-S™ cells 595:610 To reduce the production cost, we also describe a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection. 34478135 3 7 theme comparable 657:666 arg1 expression 646:655 therapeutic protein expression 626:655 therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection 626:718 To reduce the production cost, we also describe a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection. 34478135 3 8 theme therapeutic 626:636 arg1 expression 646:655 therapeutic protein expression 626:655 therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection 626:718 To reduce the production cost, we also describe a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection. 34478135 3 9 theme PEI-mediated 566:577 arg1 transfection 579:590 PEI-mediated transfection 566:590 PEI-mediated transfection in ExpiCHO-S™ cells 566:610 To reduce the production cost, we also describe a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection. 34478135 2 10 gly sialylation 462:472 arg1 glycoproteins 414:426 therapeutic glycoproteins 402:426 therapeutic glycoproteins with improved galactosylation and sialylation 402:472 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 2 11 from expression 388:397 arg1 system 488:493 ExpiCHO-S™ system 477:493 ExpiCHO-S™ system 477:493 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 3 12 theme production 510:519 arg1 cost 521:524 the production cost 506:524 the production cost 506:524 To reduce the production cost, we also describe a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection. 34478135 1 13 theme rapid 200:204 arg1 method 225:230 a rapid protein production method 198:230 a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery 198:315 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 0 14 theme Transient 12:20 arg1 Production 22:31 Large-Scale Transient Production 0:31 Large-Scale Transient Production in ExpiCHO-S™ with Enhanced N-Galactosylation-Sialylation and PEI-Based Transfection. 0:117 Large-Scale Transient Production in ExpiCHO-S™ with Enhanced N-Galactosylation-Sialylation and PEI-Based Transfection. 34478135 1 15 theme Large-scale 119:129 arg1 expression 141:150 Large-scale transient expression 119:150 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells 119:187 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 1 16 theme protein 206:212 arg1 method 225:230 a rapid protein production method 198:230 a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery 198:315 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 0 17 theme Large-Scale 0:10 arg1 Production 22:31 Large-Scale Transient Production 0:31 Large-Scale Transient Production in ExpiCHO-S™ with Enhanced N-Galactosylation-Sialylation and PEI-Based Transfection. 0:117 Large-Scale Transient Production in ExpiCHO-S™ with Enhanced N-Galactosylation-Sialylation and PEI-Based Transfection. 34478135 1 18 theme transient 131:139 arg1 expression 141:150 Large-scale transient expression 119:150 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells 119:187 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 1 19 theme production 214:223 arg1 method 225:230 a rapid protein production method 198:230 a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery 198:315 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 3 20 theme protein 638:644 arg1 expression 646:655 therapeutic protein expression 626:655 therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection 626:718 To reduce the production cost, we also describe a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection. 34478135 2 21 theme experimental 335:346 arg1 protocols 348:356 experimental protocols 335:356 experimental protocols 335:356 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 2 22 theme improved 433:440 arg1 galactosylation 442:456 improved galactosylation 433:456 improved galactosylation 433:456 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 1 23 with method 225:230 arg1 advantage 272:280 a potential start-to-end alignment advantage 237:280 a potential start-to-end alignment advantage for biotherapeutics drug discovery 237:315 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 2 24 gly glycoproteins 414:426 arg1 glycoproteins 414:426 therapeutic glycoproteins 402:426 therapeutic glycoproteins with improved galactosylation and sialylation 402:472 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 3 25 theme ExpiFectamine™-based 686:705 arg1 transfection 707:718 ExpiFectamine™-based transfection 686:718 ExpiFectamine™-based transfection 686:718 To reduce the production cost, we also describe a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection. 34478135 1 26 theme potential 239:247 arg1 advantage 272:280 a potential start-to-end alignment advantage 237:280 a potential start-to-end alignment advantage for biotherapeutics drug discovery 237:315 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 0 27 with Production 22:31 arg1 Transfection 105:116 PEI-Based Transfection 95:116 PEI-Based Transfection 95:116 Large-Scale Transient Production in ExpiCHO-S™ with Enhanced N-Galactosylation-Sialylation and PEI-Based Transfection. 34478135 0 27 with Production 22:31 arg1 N-Galactosylation-Sialylation 61:89 Enhanced N-Galactosylation-Sialylation 52:89 Enhanced N-Galactosylation-Sialylation 52:89 Large-Scale Transient Production in ExpiCHO-S™ with Enhanced N-Galactosylation-Sialylation and PEI-Based Transfection. 34478135 1 28 theme Chinese 155:161 arg1 cells 183:187 Chinese Hamster Ovary (CHO) cells 155:187 Chinese Hamster Ovary (CHO) cells 155:187 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 0 29 theme Enhanced 52:59 arg1 N-Galactosylation-Sialylation 61:89 Enhanced N-Galactosylation-Sialylation 52:89 Enhanced N-Galactosylation-Sialylation 52:89 Large-Scale Transient Production in ExpiCHO-S™ with Enhanced N-Galactosylation-Sialylation and PEI-Based Transfection. 34478135 2 30 with glycoproteins 414:426 arg1 sialylation 462:472 sialylation 462:472 sialylation 462:472 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 2 30 with glycoproteins 414:426 arg1 galactosylation 442:456 improved galactosylation 433:456 improved galactosylation 433:456 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 1 31 theme Hamster 163:169 arg1 cells 183:187 Chinese Hamster Ovary (CHO) cells 155:187 Chinese Hamster Ovary (CHO) cells 155:187 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 1 32 from expression 141:150 arg1 cells 183:187 Chinese Hamster Ovary (CHO) cells 155:187 Chinese Hamster Ovary (CHO) cells 155:187 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 1 33 theme Ovary 171:175 arg1 cells 183:187 Chinese Hamster Ovary (CHO) cells 155:187 Chinese Hamster Ovary (CHO) cells 155:187 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 1 34 theme start-to-end 249:260 arg1 advantage 272:280 a potential start-to-end alignment advantage 237:280 a potential start-to-end alignment advantage for biotherapeutics drug discovery 237:315 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 3 35 theme novel 546:550 arg1 procedure 552:560 a novel procedure 544:560 a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection 544:718 To reduce the production cost, we also describe a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection. 34478135 1 36 theme alignment 262:270 arg1 advantage 272:280 a potential start-to-end alignment advantage 237:280 a potential start-to-end alignment advantage for biotherapeutics drug discovery 237:315 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 0 37 theme PEI-Based 95:103 arg1 Transfection 105:116 PEI-Based Transfection 95:116 PEI-Based Transfection 95:116 Large-Scale Transient Production in ExpiCHO-S™ with Enhanced N-Galactosylation-Sialylation and PEI-Based Transfection. 34478135 2 38 theme ExpiCHO-S™ 477:486 arg1 system 488:493 ExpiCHO-S™ system 477:493 ExpiCHO-S™ system 477:493 In this chapter, experimental protocols are illustrated for transient expression of therapeutic glycoproteins with improved galactosylation and sialylation in ExpiCHO-S™ system. 34478135 1 39 theme CHO 178:180 arg1 cells 183:187 Chinese Hamster Ovary (CHO) cells 155:187 Chinese Hamster Ovary (CHO) cells 155:187 Large-scale transient expression in Chinese Hamster Ovary (CHO) cells provides a rapid protein production method with a potential start-to-end alignment advantage for biotherapeutics drug discovery. 34478135 3 40 theme ExpiCHO-S™ 595:604 arg1 cells 606:610 ExpiCHO-S™ cells 595:610 ExpiCHO-S™ cells 595:610 To reduce the production cost, we also describe a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection. 34478135 3 41 with level 675:679 arg1 transfection 707:718 ExpiFectamine™-based transfection 686:718 ExpiFectamine™-based transfection 686:718 To reduce the production cost, we also describe a novel procedure for PEI-mediated transfection in ExpiCHO-S™ cells that supports therapeutic protein expression comparable to the level with ExpiFectamine™-based transfection. 36952551 7 0 theme room 1295:1298 arg1 temperature 1300:1310 room temperature 1295:1310 room temperature 1295:1310 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 7 1 from temperature 1300:1310 arg1 storage 1284:1290 platelet storage 1275:1290 platelet storage at room temperature 1275:1310 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 4 2 theme tandem 639:644 arg1 spectrometry 651:662 tandem mass spectrometry 639:662 tandem mass spectrometry (MSn) 639:668 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 2 theme tandem 639:644 arg1 MSn 665:667 MSn 665:667 MSn 665:667 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 7 3 theme sialylated 1152:1161 arg1 epitopes 1163:1170 sialylated epitopes 1152:1170 sialylated epitopes 1152:1170 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 2 4 theme complex 251:257 arg1 process 259:265 a complex process 249:265 a complex process that fundamentally involves carbohydrate structures 249:317 The gradual loss of stored platelet quality is a complex process that fundamentally involves carbohydrate structures. 36952551 2 4 theme complex 251:257 arg1 loss 214:217 The gradual loss 202:217 The gradual loss of stored platelet quality 202:244 The gradual loss of stored platelet quality is a complex process that fundamentally involves carbohydrate structures. 36952551 5 5 theme complex 899:905 arg1 glycans 907:913 complex glycans 899:913 complex glycans with polylactosamine repeats 899:942 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 1 6 theme platelet 182:189 arg1 span 196:199 platelet life span 182:199 platelet life span 182:199 Changes in surface glycan determinants, specifically sialic acid loss, determine platelet life span. 36952551 3 7 link O-linked 419:426 arg1 glycans 428:434 O-linked glycans 419:434 O-linked glycans 419:434 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 5 8 theme high 874:877 arg1 structures 887:896 high mannose structures 874:896 high mannose structures 874:896 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 4 9 theme liquid 675:680 arg1 LC 698:699 LC 698:699 LC 698:699 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 9 theme liquid 675:680 arg1 chromatography 682:695 liquid chromatography 675:695 liquid chromatography (LC) 675:700 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 7 10 theme O-linked 1112:1119 arg1 glycans 1121:1127 O-linked glycans 1112:1127 O-linked glycans 1112:1127 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 7 11 theme neutral 1202:1208 arg1 structures 1210:1219 neutral structures 1202:1219 neutral structures 1202:1219 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 7 12 from activity 1256:1263 arg1 structures 1210:1219 neutral structures 1202:1219 neutral structures 1202:1219 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 8 13 theme sialylated 1344:1353 arg1 glycans 1355:1361 sialylated glycans 1344:1361 sialylated glycans 1344:1361 The data indicate that loss of sialylated glycans is associated with diminished platelet quality and untimely removal of platelets following storage. 36952551 2 14 theme gradual 206:212 arg1 loss 214:217 The gradual loss 202:217 The gradual loss of stored platelet quality 202:244 The gradual loss of stored platelet quality is a complex process that fundamentally involves carbohydrate structures. 36952551 2 14 theme gradual 206:212 arg1 process 259:265 a complex process 249:265 a complex process that fundamentally involves carbohydrate structures 249:317 The gradual loss of stored platelet quality is a complex process that fundamentally involves carbohydrate structures. 36952551 1 15 theme surface 112:118 arg1 determinants 127:138 surface glycan determinants 112:138 surface glycan determinants 112:138 Changes in surface glycan determinants, specifically sialic acid loss, determine platelet life span. 36952551 4 16 theme selected 744:751 arg1 glycans 753:759 selected glycans 744:759 selected glycans 744:759 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 5 17 theme group 974:978 arg1 epitopes 980:987 blood group epitopes 968:987 blood group epitopes 968:987 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 6 18 theme core-2 1077:1082 arg1 structures 1084:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 The O-glycan repertoire was largely comprised of sialylated and fucosylated core-1 and core-2 structures. 36952551 2 19 theme platelet 229:236 arg1 quality 238:244 stored platelet quality 222:244 stored platelet quality 222:244 The gradual loss of stored platelet quality is a complex process that fundamentally involves carbohydrate structures. 36952551 6 20 theme core-1 1066:1071 arg1 structures 1084:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 The O-glycan repertoire was largely comprised of sialylated and fucosylated core-1 and core-2 structures. 36952551 4 21 theme Analytical 517:526 arg1 methods 528:534 Analytical methods 517:534 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) 517:700 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 8 22 theme platelet 1393:1400 arg1 quality 1402:1408 diminished platelet quality 1382:1408 diminished platelet quality 1382:1408 The data indicate that loss of sialylated glycans is associated with diminished platelet quality and untimely removal of platelets following storage. 36952551 7 23 theme platelet 1275:1282 arg1 storage 1284:1290 platelet storage 1275:1290 platelet storage at room temperature 1275:1310 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 1 24 theme acid 161:164 arg1 loss 166:169 sialic acid loss 154:169 specifically sialic acid loss 141:169 Changes in surface glycan determinants, specifically sialic acid loss, determine platelet life span. 36952551 1 24 theme acid 161:164 arg1 Changes 101:107 Changes 101:107 Changes in surface glycan determinants 101:138 Changes in surface glycan determinants, specifically sialic acid loss, determine platelet life span. 36952551 0 25 theme mass 82:85 arg1 spectrometry 87:98 tandem mass spectrometry 75:98 tandem mass spectrometry 75:98 Characterization of the human platelet N- and O-glycome upon storage using tandem mass spectrometry. 36952551 3 26 theme lipophilic 337:346 arg1 protocols 378:386 lipophilic extraction and glycan release protocols 337:386 lipophilic extraction and glycan release protocols 337:386 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 7 27 theme increased 1232:1240 arg1 activity 1256:1263 increased neuraminidase activity 1232:1263 a reciprocal increase in neutral structures as well as increased neuraminidase activity 1177:1263 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 5 28 with glycans 949:955 arg1 repeats 936:942 polylactosamine repeats 920:942 polylactosamine repeats 920:942 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 8 29 theme platelets 1434:1442 arg1 quality 1402:1408 diminished platelet quality 1382:1408 diminished platelet quality 1382:1408 The data indicate that loss of sialylated glycans is associated with diminished platelet quality and untimely removal of platelets following storage. 36952551 8 29 theme platelets 1434:1442 arg1 removal 1423:1429 untimely removal 1414:1429 untimely removal of platelets following storage 1414:1460 The data indicate that loss of sialylated glycans is associated with diminished platelet quality and untimely removal of platelets following storage. 36952551 5 30 theme diverse 845:851 arg1 glycans 907:913 complex glycans 899:913 complex glycans with polylactosamine repeats 899:942 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 5 30 theme diverse 845:851 arg1 structures 887:896 high mannose structures 874:896 high mannose structures 874:896 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 5 30 theme diverse 845:851 arg1 N-glycans 853:861 diverse N-glycans 845:861 diverse N-glycans 845:861 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 5 30 theme diverse 845:851 arg1 glycans 949:955 glycans 949:955 glycans presenting blood group epitopes 949:987 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 3 31 theme release 370:376 arg1 protocols 378:386 lipophilic extraction and glycan release protocols 337:386 lipophilic extraction and glycan release protocols 337:386 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 4 32 theme mass 605:608 arg1 spectrometry 610:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry 546:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) 546:636 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 32 theme mass 605:608 arg1 MS 634:635 MALDI-TOF MS 624:635 MALDI-TOF MS 624:635 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 33 theme epitopes 774:781 arg1 details 733:739 structural details 722:739 structural details of selected glycans and terminal epitopes 722:781 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 3 34 theme room 470:473 arg1 temperature 475:485 seven-day room temperature 460:485 seven-day room temperature 460:485 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 1 35 theme glycan 120:125 arg1 determinants 127:138 surface glycan determinants 112:138 surface glycan determinants 112:138 Changes in surface glycan determinants, specifically sialic acid loss, determine platelet life span. 36952551 7 36 from loss 1144:1147 arg1 epitopes 1163:1170 sialylated epitopes 1152:1170 sialylated epitopes 1152:1170 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 0 37 theme platelet 30:37 arg1 N- 39:40 human platelet N- 24:40 human platelet N- 24:40 Characterization of the human platelet N- and O-glycome upon storage using tandem mass spectrometry. 36952551 4 38 theme assisted 553:560 arg1 spectrometry 610:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry 546:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) 546:636 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 38 theme assisted 553:560 arg1 MS 634:635 MALDI-TOF MS 624:635 MALDI-TOF MS 624:635 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 5 39 with glycans 907:913 arg1 repeats 936:942 polylactosamine repeats 920:942 polylactosamine repeats 920:942 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 6 40 gly fucosylated 1054:1064 arg1 structures 1084:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 The O-glycan repertoire was largely comprised of sialylated and fucosylated core-1 and core-2 structures. 36952551 5 41 theme structures 825:834 arg1 repertoire 803:812 The fresh platelet repertoire 784:812 The fresh platelet repertoire of surface structures 784:834 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 5 41 theme structures 825:834 arg1 structures 825:834 surface structures 817:834 surface structures 817:834 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 3 42 dep isolated 447:454 arg1 concentrates 503:514 stored platelet concentrates 487:514 stored platelet concentrates 487:514 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 4 43 theme desorption/ionization 568:588 arg1 spectrometry 610:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry 546:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) 546:636 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 43 theme desorption/ionization 568:588 arg1 MS 634:635 MALDI-TOF MS 624:635 MALDI-TOF MS 624:635 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 6 44 gly sialylated 1039:1048 arg1 structures 1084:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 The O-glycan repertoire was largely comprised of sialylated and fucosylated core-1 and core-2 structures. 36952551 3 45 theme stored 487:492 arg1 concentrates 503:514 stored platelet concentrates 487:514 stored platelet concentrates 487:514 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 1 46 from Changes 101:107 arg1 determinants 127:138 surface glycan determinants 112:138 surface glycan determinants 112:138 Changes in surface glycan determinants, specifically sialic acid loss, determine platelet life span. 36952551 4 47 theme mass 646:649 arg1 spectrometry 651:662 tandem mass spectrometry 639:662 tandem mass spectrometry (MSn) 639:668 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 47 theme mass 646:649 arg1 MSn 665:667 MSn 665:667 MSn 665:667 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 5 48 theme surface 817:823 arg1 structures 825:834 surface structures 817:834 surface structures 817:834 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 5 49 theme fresh 788:792 arg1 repertoire 803:812 The fresh platelet repertoire 784:812 The fresh platelet repertoire of surface structures 784:834 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 5 49 theme fresh 788:792 arg1 structures 825:834 surface structures 817:834 surface structures 817:834 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 8 50 gly sialylated 1344:1353 arg1 glycans 1355:1361 sialylated glycans 1344:1361 sialylated glycans 1344:1361 The data indicate that loss of sialylated glycans is associated with diminished platelet quality and untimely removal of platelets following storage. 36952551 7 51 theme reciprocal 1179:1188 arg1 increase 1190:1197 a reciprocal increase 1177:1197 a reciprocal increase in neutral structures as well as increased neuraminidase activity 1177:1263 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 5 52 theme platelet 794:801 arg1 repertoire 803:812 The fresh platelet repertoire 784:812 The fresh platelet repertoire of surface structures 784:834 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 5 52 theme platelet 794:801 arg1 structures 825:834 surface structures 817:834 surface structures 817:834 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 7 53 from increase 1190:1197 arg1 structures 1210:1219 neutral structures 1202:1219 neutral structures 1202:1219 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 2 54 theme carbohydrate 295:306 arg1 structures 308:317 carbohydrate structures 295:317 carbohydrate structures 295:317 The gradual loss of stored platelet quality is a complex process that fundamentally involves carbohydrate structures. 36952551 1 55 theme life 191:194 arg1 span 196:199 platelet life span 182:199 platelet life span 182:199 Changes in surface glycan determinants, specifically sialic acid loss, determine platelet life span. 36952551 2 56 theme stored 222:227 arg1 quality 238:244 stored platelet quality 222:244 stored platelet quality 222:244 The gradual loss of stored platelet quality is a complex process that fundamentally involves carbohydrate structures. 36952551 5 57 theme mannose 879:885 arg1 structures 887:896 high mannose structures 874:896 high mannose structures 874:896 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 6 58 theme O-glycan 994:1001 arg1 repertoire 1003:1012 The O-glycan repertoire 990:1012 The O-glycan repertoire 990:1012 The O-glycan repertoire was largely comprised of sialylated and fucosylated core-1 and core-2 structures. 36952551 4 59 theme structural 722:731 arg1 details 733:739 structural details 722:739 structural details of selected glycans and terminal epitopes 722:781 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 5 60 theme blood 968:972 arg1 epitopes 980:987 blood group epitopes 968:987 blood group epitopes 968:987 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 8 61 theme glycans 1355:1361 arg1 loss 1336:1339 loss 1336:1339 loss of sialylated glycans 1336:1361 The data indicate that loss of sialylated glycans is associated with diminished platelet quality and untimely removal of platelets following storage. 36952551 2 62 theme quality 238:244 arg1 loss 214:217 The gradual loss 202:217 The gradual loss of stored platelet quality 202:244 The gradual loss of stored platelet quality is a complex process that fundamentally involves carbohydrate structures. 36952551 2 62 theme quality 238:244 arg1 process 259:265 a complex process 249:265 a complex process that fundamentally involves carbohydrate structures 249:317 The gradual loss of stored platelet quality is a complex process that fundamentally involves carbohydrate structures. 36952551 5 63 theme polylactosamine 920:934 arg1 repeats 936:942 polylactosamine repeats 920:942 polylactosamine repeats 920:942 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 0 64 theme tandem 75:80 arg1 spectrometry 87:98 tandem mass spectrometry 75:98 tandem mass spectrometry 75:98 Characterization of the human platelet N- and O-glycome upon storage using tandem mass spectrometry. 36952551 3 65 from N- 412:413 arg1 isolated 447:454 isolated 447:454 isolated 447:454 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 3 65 from N- 412:413 arg1 temperature 475:485 seven-day room temperature 460:485 seven-day room temperature 460:485 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 1 66 theme sialic 154:159 arg1 loss 166:169 sialic acid loss 154:169 specifically sialic acid loss 141:169 Changes in surface glycan determinants, specifically sialic acid loss, determine platelet life span. 36952551 1 66 theme sialic 154:159 arg1 Changes 101:107 Changes 101:107 Changes in surface glycan determinants 101:138 Changes in surface glycan determinants, specifically sialic acid loss, determine platelet life span. 36952551 6 67 theme fucosylated 1054:1064 arg1 structures 1084:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 The O-glycan repertoire was largely comprised of sialylated and fucosylated core-1 and core-2 structures. 36952551 4 68 theme matrix 546:551 arg1 spectrometry 610:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry 546:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) 546:636 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 68 theme matrix 546:551 arg1 MS 634:635 MALDI-TOF MS 624:635 MALDI-TOF MS 624:635 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 8 69 theme diminished 1382:1391 arg1 quality 1402:1408 diminished platelet quality 1382:1408 diminished platelet quality 1382:1408 The data indicate that loss of sialylated glycans is associated with diminished platelet quality and untimely removal of platelets following storage. 36952551 7 70 theme neuraminidase 1242:1254 arg1 activity 1256:1263 increased neuraminidase activity 1232:1263 a reciprocal increase in neutral structures as well as increased neuraminidase activity 1177:1263 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 6 71 theme sialylated 1039:1048 arg1 structures 1084:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 sialylated and fucosylated core-1 and core-2 structures 1039:1093 The O-glycan repertoire was largely comprised of sialylated and fucosylated core-1 and core-2 structures. 36952551 3 72 theme glycan 363:368 arg1 release 370:376 glycan release 363:376 glycan release 363:376 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 3 73 theme extraction 348:357 arg1 protocols 378:386 lipophilic extraction and glycan release protocols 337:386 lipophilic extraction and glycan release protocols 337:386 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 8 74 theme untimely 1414:1421 arg1 removal 1423:1429 untimely removal 1414:1429 untimely removal of platelets following storage 1414:1460 The data indicate that loss of sialylated glycans is associated with diminished platelet quality and untimely removal of platelets following storage. 36952551 4 75 theme glycans 753:759 arg1 details 733:739 structural details 722:739 structural details of selected glycans and terminal epitopes 722:781 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 0 76 theme human 24:28 arg1 N- 39:40 human platelet N- 24:40 human platelet N- 24:40 Characterization of the human platelet N- and O-glycome upon storage using tandem mass spectrometry. 36952551 4 77 used used 707:710 arg2 methods 528:534 Analytical methods 517:534 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) 517:700 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 78 theme MALDI-TOF 624:632 arg1 spectrometry 610:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry 546:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) 546:636 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 78 theme MALDI-TOF 624:632 arg1 MS 634:635 MALDI-TOF MS 624:635 MALDI-TOF MS 624:635 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 5 79 with structures 887:896 arg1 repeats 936:942 polylactosamine repeats 920:942 polylactosamine repeats 920:942 The fresh platelet repertoire of surface structures revealed diverse N-glycans, including high mannose structures, complex glycans with polylactosamine repeats, and glycans presenting blood group epitopes. 36952551 4 80 theme terminal 765:772 arg1 epitopes 774:781 terminal epitopes 765:781 terminal epitopes 765:781 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 0 81 theme N- 39:40 arg1 Characterization 0:15 Characterization 0:15 Characterization of the human platelet N- and O-glycome upon storage using tandem mass spectrometry. 0:99 Characterization of the human platelet N- and O-glycome upon storage using tandem mass spectrometry. 36952551 7 82 gly sialylated 1152:1161 arg1 epitopes 1163:1170 sialylated epitopes 1152:1170 sialylated epitopes 1152:1170 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36952551 3 83 theme O-linked 419:426 arg1 glycans 428:434 O-linked glycans 419:434 O-linked glycans 419:434 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 4 84 theme laser 562:566 arg1 spectrometry 610:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry 546:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) 546:636 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 84 theme laser 562:566 arg1 MS 634:635 MALDI-TOF MS 624:635 MALDI-TOF MS 624:635 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 3 85 theme seven-day 460:468 arg1 temperature 475:485 seven-day room temperature 460:485 seven-day room temperature 460:485 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 0 86 theme O-glycome 46:54 arg1 Characterization 0:15 Characterization 0:15 Characterization of the human platelet N- and O-glycome upon storage using tandem mass spectrometry. 0:99 Characterization of the human platelet N- and O-glycome upon storage using tandem mass spectrometry. 36952551 4 87 theme time-of-flight 590:603 arg1 spectrometry 610:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry 546:621 matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) 546:636 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 4 87 theme time-of-flight 590:603 arg1 MS 634:635 MALDI-TOF MS 624:635 MALDI-TOF MS 624:635 Analytical methods including matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MSn), and liquid chromatography (LC) were used to obtain structural details of selected glycans and terminal epitopes. 36952551 3 88 from glycans 428:434 arg1 isolated 447:454 isolated 447:454 isolated 447:454 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 3 88 from glycans 428:434 arg1 temperature 475:485 seven-day room temperature 460:485 seven-day room temperature 460:485 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 3 89 theme platelet 494:501 arg1 concentrates 503:514 stored platelet concentrates 487:514 stored platelet concentrates 487:514 Here, we applied lipophilic extraction and glycan release protocols to sequentially profile N- and O-linked glycans in freshly isolated and seven-day room temperature stored platelet concentrates. 36952551 7 90 link O-linked 1112:1119 arg1 glycans 1121:1127 O-linked glycans 1112:1127 O-linked glycans 1112:1127 For both N- and O-linked glycans, we observed a loss in sialylated epitopes with a reciprocal increase in neutral structures as well as increased neuraminidase activity following platelet storage at room temperature. 36714768 9 0 theme plant 1666:1670 arg1 wall 1677:1680 the plant cell wall 1662:1680 the plant cell wall 1662:1680 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 0 1 from synthesis 21:29 arg1 plants 41:46 higher plants 34:46 higher plants 34:46 β-1,4-Xylan backbone synthesis in higher plants: How complex can it be? 36714768 9 2 theme dynamic 1517:1523 arg1 means 1555:1559 a means 1553:1559 a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall 1553:1680 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 9 2 theme dynamic 1517:1523 arg1 changes 1525:1531 potential dynamic changes 1507:1531 potential dynamic changes of the XSC 1507:1542 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 5 3 theme cell 800:803 arg1 wall 805:808 the primary cell wall 788:808 the primary cell wall of the eudicot Arabidopsis thaliana 788:844 Here, we argue that an equivalent XSC exists for the synthesis of the primary cell wall of the eudicot Arabidopsis thaliana, consisting of IRX9L, IRX10L and IRX14. 36714768 8 4 theme Golgi 1481:1485 arg1 apparatus 1487:1495 the Golgi apparatus 1477:1495 the Golgi apparatus 1477:1495 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 7 5 theme non-catalytic 1208:1220 arg1 function 1222:1229 non-catalytic function 1208:1229 non-catalytic function 1208:1229 In contrast to the CSC, in which each CESA protein has catalytic activity, the XSC seems to contain proteins with non-catalytic function with each component bearing potentially unique but crucial roles. 36714768 8 6 theme IRX10/IRX10L 1359:1370 arg1 combination 1332:1342 a combination 1330:1342 a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L 1330:1387 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 9 7 theme coordinated 1608:1618 arg1 deposition 1620:1629 coordinated deposition 1608:1629 coordinated deposition of tailored polysaccharides in the plant cell wall 1608:1680 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 5 8 theme wall 805:808 arg1 synthesis 775:783 the synthesis 771:783 the synthesis 771:783 Here, we argue that an equivalent XSC exists for the synthesis of the primary cell wall of the eudicot Arabidopsis thaliana, consisting of IRX9L, IRX10L and IRX14. 36714768 4 9 dep asparagus 588:596 arg1 AoIRX14A 618:625 AoIRX14A 618:625 AoIRX14A 618:625 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 4 9 dep asparagus 588:596 arg1 AoIRX10 606:612 AoIRX10 606:612 AoIRX10 606:612 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 4 9 dep asparagus 588:596 arg1 AoIRX9 598:603 AoIRX9 598:603 AoIRX9 598:603 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 8 10 from stable 1402:1407 arg1 composition 1416:1426 its composition 1412:1426 its composition during transit from the endoplasmic reticulum to the Golgi apparatus 1412:1495 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 4 11 theme secondary 682:690 arg1 biosynthesis 708:719 secondary cell wall xylan biosynthesis 682:719 secondary cell wall xylan biosynthesis 682:719 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 6 12 theme synthesis 1027:1035 arg1 CSCs 1048:1051 CSCs 1048:1051 CSCs 1048:1051 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 6 12 theme synthesis 1027:1035 arg1 complexes 1037:1045 the distinct cellulose synthesis complexes 1004:1045 the distinct cellulose synthesis complexes (CSCs) 1004:1052 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 5 13 theme thaliana 837:844 arg1 wall 805:808 the primary cell wall 788:808 the primary cell wall of the eudicot Arabidopsis thaliana 788:844 Here, we argue that an equivalent XSC exists for the synthesis of the primary cell wall of the eudicot Arabidopsis thaliana, consisting of IRX9L, IRX10L and IRX14. 36714768 8 14 theme IRX14/IRX14L 1376:1387 arg1 combination 1332:1342 a combination 1330:1342 a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L 1330:1387 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 6 15 theme cell 1083:1086 arg1 wall 1088:1091 the primary and secondary cell wall 1057:1091 the primary and secondary cell wall 1057:1091 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 7 16 contain has 1145:1147 arg2 activity 1159:1166 catalytic activity 1149:1166 catalytic activity 1149:1166 In contrast to the CSC, in which each CESA protein has catalytic activity, the XSC seems to contain proteins with non-catalytic function with each component bearing potentially unique but crucial roles. 36714768 7 16 contain has 1145:1147 arg1 protein 1137:1143 each CESA protein 1127:1143 each CESA protein 1127:1143 In contrast to the CSC, in which each CESA protein has catalytic activity, the XSC seems to contain proteins with non-catalytic function with each component bearing potentially unique but crucial roles. 36714768 7 17 theme unique 1271:1276 arg1 roles 1290:1294 potentially unique but crucial roles 1259:1294 potentially unique but crucial roles 1259:1294 In contrast to the CSC, in which each CESA protein has catalytic activity, the XSC seems to contain proteins with non-catalytic function with each component bearing potentially unique but crucial roles. 36714768 9 18 theme polysaccharides 1643:1657 arg1 deposition 1620:1629 coordinated deposition 1608:1629 coordinated deposition of tailored polysaccharides in the plant cell wall 1608:1680 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 6 19 theme cellulose 1017:1025 arg1 CSCs 1048:1051 CSCs 1048:1051 CSCs 1048:1051 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 6 19 theme cellulose 1017:1025 arg1 complexes 1037:1045 the distinct cellulose synthesis complexes 1004:1045 the distinct cellulose synthesis complexes (CSCs) 1004:1052 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 5 20 theme equivalent 745:754 arg1 XSC 756:758 an equivalent XSC 742:758 an equivalent XSC 742:758 Here, we argue that an equivalent XSC exists for the synthesis of the primary cell wall of the eudicot Arabidopsis thaliana, consisting of IRX9L, IRX10L and IRX14. 36714768 1 21 from walls 117:121 arg1 present 97:103 present 97:103 present 97:103 Xylan is a hemicellulose present in the cell walls of all land plants. 36714768 2 22 theme families 230:237 arg1 Glycosyltransferases 143:162 Glycosyltransferases 143:162 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families 143:237 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 2 23 mod modified 330:337 arg3 chains 369:374 sugar side chains 358:374 sugar side chains 358:374 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 2 23 mod modified 330:337 arg1 backbone 299:306 its β-1,4-linked xylose backbone 275:306 its β-1,4-linked xylose backbone 275:306 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 2 23 mod modified 330:337 arg3 acetylation 342:352 acetylation 342:352 acetylation 342:352 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 1 24 theme land 130:133 arg1 plants 135:140 all land plants 126:140 all land plants 126:140 Xylan is a hemicellulose present in the cell walls of all land plants. 36714768 8 25 from composition 1416:1426 arg1 XSC 1316:1318 the core XSC 1307:1318 the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L 1307:1387 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 8 25 from composition 1416:1426 arg1 stable 1402:1407 stable 1402:1407 stable 1402:1407 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 4 26 theme cell 692:695 arg1 biosynthesis 708:719 secondary cell wall xylan biosynthesis 682:719 secondary cell wall xylan biosynthesis 682:719 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 6 27 theme xylan 972:976 arg1 synthesis 978:986 primary and secondary cell wall xylan synthesis 940:986 primary and secondary cell wall xylan synthesis 940:986 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 1 28 theme plants 135:140 arg1 walls 117:121 the cell walls 108:121 the cell walls of all land plants 108:140 Xylan is a hemicellulose present in the cell walls of all land plants. 36714768 0 29 theme backbone 12:19 arg1 synthesis 21:29 β-1,4-Xylan backbone synthesis 0:29 β-1,4-Xylan backbone synthesis in higher plants 0:46 β-1,4-Xylan backbone synthesis in higher plants: How complex can it be? 36714768 6 30 theme wall 967:970 arg1 synthesis 978:986 primary and secondary cell wall xylan synthesis 940:986 primary and secondary cell wall xylan synthesis 940:986 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 0 31 dep be 68:69 arg1 synthesis 21:29 β-1,4-Xylan backbone synthesis 0:29 β-1,4-Xylan backbone synthesis in higher plants 0:46 β-1,4-Xylan backbone synthesis in higher plants: How complex can it be? 36714768 0 31 dep be 68:69 arg1 complex 53:59 complex 53:59 complex 53:59 β-1,4-Xylan backbone synthesis in higher plants: How complex can it be? 36714768 6 32 theme secondary 952:960 arg1 synthesis 978:986 primary and secondary cell wall xylan synthesis 940:986 primary and secondary cell wall xylan synthesis 940:986 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 6 33 theme distinct 1008:1015 arg1 CSCs 1048:1051 CSCs 1048:1051 CSCs 1048:1051 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 6 33 theme distinct 1008:1015 arg1 complexes 1037:1045 the distinct cellulose synthesis complexes 1004:1045 the distinct cellulose synthesis complexes (CSCs) 1004:1052 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 0 34 theme β-1,4-Xylan 0:10 arg1 synthesis 21:29 β-1,4-Xylan backbone synthesis 0:29 β-1,4-Xylan backbone synthesis in higher plants 0:46 β-1,4-Xylan backbone synthesis in higher plants: How complex can it be? 36714768 6 35 theme secondary 1073:1081 arg1 wall 1088:1091 the primary and secondary cell wall 1057:1091 the primary and secondary cell wall 1057:1091 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 7 36 contain contain 1186:1192 arg1 XSC 1173:1175 the XSC 1169:1175 the XSC 1169:1175 In contrast to the CSC, in which each CESA protein has catalytic activity, the XSC seems to contain proteins with non-catalytic function with each component bearing potentially unique but crucial roles. 36714768 7 36 contain contain 1186:1192 arg2 proteins 1194:1201 proteins 1194:1201 proteins with non-catalytic function 1194:1229 In contrast to the CSC, in which each CESA protein has catalytic activity, the XSC seems to contain proteins with non-catalytic function with each component bearing potentially unique but crucial roles. 36714768 8 37 from reticulum 1464:1472 arg1 transit 1435:1441 transit 1435:1441 transit from the endoplasmic reticulum to the Golgi apparatus 1435:1495 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 4 38 theme asparagus 588:596 arg1 co-expression 571:583 co-expression 571:583 co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A 571:625 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 9 39 theme cell 1672:1675 arg1 wall 1677:1680 the plant cell wall 1662:1680 the plant cell wall 1662:1680 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 4 40 theme synthesis 487:495 arg1 complex 497:503 A xylan synthesis complex 479:503 A xylan synthesis complex (XSC) 479:509 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 4 40 theme synthesis 487:495 arg1 XSC 506:508 XSC 506:508 XSC 506:508 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 9 41 theme tailored 1634:1641 arg1 polysaccharides 1643:1657 tailored polysaccharides 1634:1657 tailored polysaccharides 1634:1657 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 1 42 from present 97:103 arg1 walls 117:121 the cell walls 108:121 the cell walls of all land plants 108:140 Xylan is a hemicellulose present in the cell walls of all land plants. 36714768 6 43 theme complexes 1037:1045 arg1 reminiscent 989:999 reminiscent 989:999 reminiscent of the distinct cellulose synthesis complexes (CSCs) 989:1052 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 6 43 theme complexes 1037:1045 arg1 XSCs 931:934 distinct XSCs 922:934 distinct XSCs for primary and secondary cell wall xylan synthesis 922:986 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 8 44 theme IRX9/IRX9L 1347:1356 arg1 combination 1332:1342 a combination 1330:1342 a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L 1330:1387 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 6 45 theme primary 940:946 arg1 synthesis 978:986 primary and secondary cell wall xylan synthesis 940:986 primary and secondary cell wall xylan synthesis 940:986 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 4 46 theme wall 697:700 arg1 biosynthesis 708:719 secondary cell wall xylan biosynthesis 682:719 secondary cell wall xylan biosynthesis 682:719 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 6 47 theme primary 1061:1067 arg1 wall 1088:1091 the primary and secondary cell wall 1057:1091 the primary and secondary cell wall 1057:1091 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 4 48 theme active 663:668 arg1 complex 670:676 a catalytically active complex 647:676 a catalytically active complex for secondary cell wall xylan biosynthesis 647:719 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 2 49 theme side 364:367 arg1 chains 369:374 sugar side chains 358:374 sugar side chains 358:374 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 7 50 theme catalytic 1149:1157 arg1 activity 1159:1166 catalytic activity 1149:1166 catalytic activity 1149:1166 In contrast to the CSC, in which each CESA protein has catalytic activity, the XSC seems to contain proteins with non-catalytic function with each component bearing potentially unique but crucial roles. 36714768 2 51 theme xylose 292:297 arg1 backbone 299:306 its β-1,4-linked xylose backbone 275:306 its β-1,4-linked xylose backbone 275:306 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 9 52 theme XSC 1540:1542 arg1 means 1555:1559 a means 1553:1559 a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall 1553:1680 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 9 52 theme XSC 1540:1542 arg1 changes 1525:1531 potential dynamic changes 1507:1531 potential dynamic changes of the XSC 1507:1542 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 6 53 theme XSCs 931:934 arg1 existence 909:917 the existence 905:917 the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall 905:1091 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 2 54 theme sugar 358:362 arg1 chains 369:374 sugar side chains 358:374 sugar side chains 358:374 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 0 55 theme higher 34:39 arg1 plants 41:46 higher plants 34:46 higher plants 34:46 β-1,4-Xylan backbone synthesis in higher plants: How complex can it be? 36714768 6 56 theme distinct 922:929 arg1 reminiscent 989:999 reminiscent 989:999 reminiscent of the distinct cellulose synthesis complexes (CSCs) 989:1052 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 6 56 theme distinct 922:929 arg1 XSCs 931:934 distinct XSCs 922:934 distinct XSCs for primary and secondary cell wall xylan synthesis 922:986 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 8 57 theme core 1311:1314 arg1 XSC 1316:1318 the core XSC 1307:1318 the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L 1307:1387 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 8 57 theme core 1311:1314 arg1 stable 1402:1407 stable 1402:1407 stable 1402:1407 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 2 58 theme backbone 299:306 arg1 biosynthesis 259:270 the biosynthesis 255:270 the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains 255:374 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 4 59 theme xylan 481:485 arg1 complex 497:503 A xylan synthesis complex 479:503 A xylan synthesis complex (XSC) 479:509 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 4 59 theme xylan 481:485 arg1 XSC 506:508 XSC 506:508 XSC 506:508 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 1 60 attach present 97:103 arg2 hemicellulose 83:95 a hemicellulose 81:95 a hemicellulose present in the cell walls of all land plants 81:140 Xylan is a hemicellulose present in the cell walls of all land plants. 36714768 1 60 attach present 97:103 arg2 Xylan 72:76 Xylan 72:76 Xylan 72:76 Xylan is a hemicellulose present in the cell walls of all land plants. 36714768 1 60 attach present 97:103 arg1 walls 117:121 the cell walls 108:121 the cell walls of all land plants 108:140 Xylan is a hemicellulose present in the cell walls of all land plants. 36714768 9 61 from deposition 1620:1629 arg1 wall 1677:1680 the plant cell wall 1662:1680 the plant cell wall 1662:1680 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 4 62 dep monocots 537:544 arg1 monocots 537:544 the monocots wheat and asparagus 533:564 the monocots wheat and asparagus 533:564 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 4 62 dep monocots 537:544 arg1 asparagus 556:564 asparagus 556:564 asparagus 556:564 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 4 62 dep monocots 537:544 arg1 wheat 546:550 wheat 546:550 wheat 546:550 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 7 63 theme CESA 1132:1135 arg1 protein 1137:1143 each CESA protein 1127:1143 each CESA protein 1127:1143 In contrast to the CSC, in which each CESA protein has catalytic activity, the XSC seems to contain proteins with non-catalytic function with each component bearing potentially unique but crucial roles. 36714768 1 64 theme present 97:103 arg1 Xylan 72:76 Xylan 72:76 Xylan 72:76 Xylan is a hemicellulose present in the cell walls of all land plants. 36714768 1 64 theme present 97:103 arg1 hemicellulose 83:95 a hemicellulose 81:95 a hemicellulose present in the cell walls of all land plants 81:140 Xylan is a hemicellulose present in the cell walls of all land plants. 36714768 9 65 theme xylan 1575:1579 arg1 biosynthesis 1581:1592 xylan biosynthesis 1575:1592 xylan biosynthesis 1575:1592 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 2 66 theme GT43 171:174 arg1 families 230:237 the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families 167:237 the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families 167:237 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 6 67 theme wall 1088:1091 arg1 existence 909:917 the existence 905:917 the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall 905:1091 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 7 68 theme crucial 1282:1288 arg1 roles 1290:1294 potentially unique but crucial roles 1259:1294 potentially unique but crucial roles 1259:1294 In contrast to the CSC, in which each CESA protein has catalytic activity, the XSC seems to contain proteins with non-catalytic function with each component bearing potentially unique but crucial roles. 36714768 2 69 theme β-1,4-linked 279:290 arg1 backbone 299:306 its β-1,4-linked xylose backbone 275:306 its β-1,4-linked xylose backbone 275:306 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 8 70 theme endoplasmic 1452:1462 arg1 reticulum 1464:1472 the endoplasmic reticulum 1448:1472 the endoplasmic reticulum to the Golgi apparatus 1448:1495 Moreover, the core XSC formed by a combination of IRX9/IRX9L, IRX10/IRX10L and IRX14/IRX14L might not be stable in its composition during transit from the endoplasmic reticulum to the Golgi apparatus. 36714768 5 71 theme eudicot 817:823 arg1 thaliana 837:844 the eudicot Arabidopsis thaliana 813:844 the eudicot Arabidopsis thaliana 813:844 Here, we argue that an equivalent XSC exists for the synthesis of the primary cell wall of the eudicot Arabidopsis thaliana, consisting of IRX9L, IRX10L and IRX14. 36714768 4 72 theme xylan 702:706 arg1 biosynthesis 708:719 secondary cell wall xylan biosynthesis 682:719 secondary cell wall xylan biosynthesis 682:719 A xylan synthesis complex (XSC) has been described in the monocots wheat and asparagus, and co-expression of asparagus AoIRX9, AoIRX10 and AoIRX14A is required to form a catalytically active complex for secondary cell wall xylan biosynthesis. 36714768 5 73 theme Arabidopsis 825:835 arg1 thaliana 837:844 the eudicot Arabidopsis thaliana 813:844 the eudicot Arabidopsis thaliana 813:844 Here, we argue that an equivalent XSC exists for the synthesis of the primary cell wall of the eudicot Arabidopsis thaliana, consisting of IRX9L, IRX10L and IRX14. 36714768 3 74 theme different 413:421 arg1 enzymes 423:429 the different enzymes 409:429 the different enzymes 409:429 However, it remains unclear how the different enzymes work together to synthesize the xylan backbone. 36714768 9 75 theme potential 1507:1515 arg1 means 1555:1559 a means 1553:1559 a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall 1553:1680 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 9 75 theme potential 1507:1515 arg1 changes 1525:1531 potential dynamic changes 1507:1531 potential dynamic changes of the XSC 1507:1542 Instead, potential dynamic changes of the XSC might be a means of regulating xylan biosynthesis to facilitate coordinated deposition of tailored polysaccharides in the plant cell wall. 36714768 5 76 theme primary 792:798 arg1 wall 805:808 the primary cell wall 788:808 the primary cell wall of the eudicot Arabidopsis thaliana 788:844 Here, we argue that an equivalent XSC exists for the synthesis of the primary cell wall of the eudicot Arabidopsis thaliana, consisting of IRX9L, IRX10L and IRX14. 36714768 2 77 theme GT47 210:213 arg1 families 230:237 the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families 167:237 the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families 167:237 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 1 78 theme cell 112:115 arg1 walls 117:121 the cell walls 108:121 the cell walls of all land plants 108:140 Xylan is a hemicellulose present in the cell walls of all land plants. 36714768 6 79 theme cell 962:965 arg1 synthesis 978:986 primary and secondary cell wall xylan synthesis 940:986 primary and secondary cell wall xylan synthesis 940:986 This would suggest the existence of distinct XSCs for primary and secondary cell wall xylan synthesis, reminiscent of the distinct cellulose synthesis complexes (CSCs) of the primary and secondary cell wall. 36714768 7 80 with proteins 1194:1201 arg1 function 1222:1229 non-catalytic function 1208:1229 non-catalytic function 1208:1229 In contrast to the CSC, in which each CESA protein has catalytic activity, the XSC seems to contain proteins with non-catalytic function with each component bearing potentially unique but crucial roles. 36714768 2 81 link β-1,4-linked 279:290 arg1 backbone 299:306 its β-1,4-linked xylose backbone 275:306 its β-1,4-linked xylose backbone 275:306 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 3 82 theme xylan 463:467 arg1 backbone 469:476 the xylan backbone 459:476 the xylan backbone 459:476 However, it remains unclear how the different enzymes work together to synthesize the xylan backbone. 36714768 2 83 dep GT43 171:174 arg1 IRX14/IRX14L 192:203 IRX14/IRX14L 192:203 IRX14/IRX14L 192:203 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36714768 2 83 dep GT43 171:174 arg1 IRX9/IRX9L 177:186 IRX9/IRX9L 177:186 IRX9/IRX9L 177:186 Glycosyltransferases of the GT43 (IRX9/IRX9L and IRX14/IRX14L) and GT47 (IRX10/IRX10L) families are involved in the biosynthesis of its β-1,4-linked xylose backbone, which can be further modified by acetylation and sugar side chains. 36673398 0 0 theme Grain 83:87 arg1 Pericarp 89:96 Sorghum Grain Pericarp 75:96 Sorghum Grain Pericarp 75:96 Formulation of a Synergistic Enzyme Cocktail for Controlled Degradation of Sorghum Grain Pericarp. 36673398 7 1 theme hydrolysed 1464:1473 arg1 sugars 1475:1480 more hydrolysed sugars 1459:1480 more hydrolysed sugars 1459:1480 The results showed that the xylanase enzyme has a major effect on the grain bran composition compared to cellulase and pectinase; however, a synergistic mixture yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually. 36673398 6 2 theme incubation 1278:1287 arg1 period 1268:1273 a certain period 1258:1273 a certain period of incubation 1258:1287 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 8 3 theme crystallinity 1610:1622 arg1 studies 1624:1630 morphological and crystallinity studies 1592:1630 morphological and crystallinity studies of the soaked grain 1592:1650 The results were confirmed by morphological and crystallinity studies of the soaked grain. 36673398 0 4 theme Sorghum 75:81 arg1 Pericarp 89:96 Sorghum Grain Pericarp 75:96 Sorghum Grain Pericarp 75:96 Formulation of a Synergistic Enzyme Cocktail for Controlled Degradation of Sorghum Grain Pericarp. 36673398 9 5 theme degraded 1815:1822 arg1 layers 1830:1835 visibly thinner and more degraded fibre layers 1790:1835 visibly thinner and more degraded fibre layers 1790:1835 Compared to conventional water-soaked samples, grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase had visibly thinner and more degraded fibre layers. 36673398 9 6 theme xylanase 1739:1746 arg1 % 1737:1737 66.7% xylanase 1733:1746 66.7% xylanase 1733:1746 Compared to conventional water-soaked samples, grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase had visibly thinner and more degraded fibre layers. 36673398 3 7 theme traditional 481:491 arg1 practices 501:509 traditional milling practices 481:509 traditional milling practices 481:509 Grain breakage and loss of essential nutrients also disadvantage traditional milling practices. 36673398 6 8 from yield 1203:1207 arg1 extract 1244:1250 the pericarp extract 1231:1250 the pericarp extract 1231:1250 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 4 9 theme grain 566:570 arg1 pericarp 572:579 the grain pericarp 562:579 the grain pericarp 562:579 Using carbohydrate degrading enzymes to hydrolyse the grain pericarp is a novel approach to biopolishing, where selective degradation of the pericarp layers occurs without adversely affecting the nutrient profile. 36673398 8 10 theme grain 1646:1650 arg1 studies 1624:1630 morphological and crystallinity studies 1592:1630 morphological and crystallinity studies of the soaked grain 1592:1650 The results were confirmed by morphological and crystallinity studies of the soaked grain. 36673398 6 11 theme certain 1260:1266 arg1 period 1268:1273 a certain period 1258:1273 a certain period of incubation 1258:1287 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 3 12 theme milling 493:499 arg1 practices 501:509 traditional milling practices 481:509 traditional milling practices 481:509 Grain breakage and loss of essential nutrients also disadvantage traditional milling practices. 36673398 5 13 theme sugars 952:957 arg1 variety 941:947 a variety 939:947 a variety of sugars that show specific degradation with respect to each enzyme 939:1016 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 5 13 theme sugars 952:957 arg1 sugars 952:957 sugars 952:957 sugars that show specific degradation with respect to each enzyme 952:1016 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 6 14 from xylanase 1085:1092 arg1 proportions 1133:1143 different proportions 1123:1143 different proportions for hydrolysing sorghum grain pericarp 1123:1182 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 0 15 theme Pericarp 89:96 arg1 Degradation 60:70 Controlled Degradation 49:70 Controlled Degradation of Sorghum Grain Pericarp 49:96 Formulation of a Synergistic Enzyme Cocktail for Controlled Degradation of Sorghum Grain Pericarp. 36673398 6 16 theme grain 1169:1173 arg1 pericarp 1175:1182 hydrolysing sorghum grain pericarp 1149:1182 hydrolysing sorghum grain pericarp 1149:1182 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 2 17 theme food 300:303 arg1 formulations 305:316 conventional food formulations 287:316 conventional food formulations 287:316 However, the utilisation of whole grain sorghum as an ingredient in conventional food formulations is limited due to its poor digestibility, which requires the removal of the outer fibrous layers. 36673398 9 18 theme cellulase 1755:1763 arg1 % 1753:1753 16.7% cellulase 1749:1763 16.7% cellulase 1749:1763 Compared to conventional water-soaked samples, grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase had visibly thinner and more degraded fibre layers. 36673398 4 19 theme nutrient 708:715 arg1 profile 717:723 the nutrient profile 704:723 the nutrient profile 704:723 Using carbohydrate degrading enzymes to hydrolyse the grain pericarp is a novel approach to biopolishing, where selective degradation of the pericarp layers occurs without adversely affecting the nutrient profile. 36673398 7 20 theme grain 1360:1364 arg1 composition 1371:1381 the grain bran composition 1356:1381 the grain bran composition 1356:1381 The results showed that the xylanase enzyme has a major effect on the grain bran composition compared to cellulase and pectinase; however, a synergistic mixture yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually. 36673398 2 21 theme grain 253:257 arg1 utilisation 232:242 the utilisation 228:242 the utilisation of whole grain sorghum as an ingredient in conventional food formulations 228:316 However, the utilisation of whole grain sorghum as an ingredient in conventional food formulations is limited due to its poor digestibility, which requires the removal of the outer fibrous layers. 36673398 5 22 theme non-starch 868:877 arg1 polysaccharides 879:893 non-starch polysaccharides 868:893 non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme 868:1016 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 6 23 theme enzyme 1064:1069 arg1 cocktail 1071:1078 such an enzyme cocktail 1056:1078 such an enzyme cocktail 1056:1078 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 6 24 from extract 1244:1250 arg1 yield 1203:1207 the yield 1199:1207 the yield of specific sugars in the pericarp extract 1199:1250 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 9 25 theme thinner 1798:1804 arg1 layers 1830:1835 visibly thinner and more degraded fibre layers 1790:1835 visibly thinner and more degraded fibre layers 1790:1835 Compared to conventional water-soaked samples, grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase had visibly thinner and more degraded fibre layers. 36673398 2 26 theme whole 247:251 arg1 grain 253:257 whole grain sorghum 247:265 whole grain sorghum 247:265 However, the utilisation of whole grain sorghum as an ingredient in conventional food formulations is limited due to its poor digestibility, which requires the removal of the outer fibrous layers. 36673398 7 27 theme xylanase 1318:1325 arg1 enzyme 1327:1332 the xylanase enzyme 1314:1332 the xylanase enzyme 1314:1332 The results showed that the xylanase enzyme has a major effect on the grain bran composition compared to cellulase and pectinase; however, a synergistic mixture yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually. 36673398 6 28 theme pericarp 1235:1242 arg1 extract 1244:1250 the pericarp extract 1231:1250 the pericarp extract 1231:1250 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 2 29 theme conventional 287:298 arg1 formulations 305:316 conventional food formulations 287:316 conventional food formulations 287:316 However, the utilisation of whole grain sorghum as an ingredient in conventional food formulations is limited due to its poor digestibility, which requires the removal of the outer fibrous layers. 36673398 7 30 theme synergistic 1431:1441 arg1 mixture 1443:1449 a synergistic mixture 1429:1449 a synergistic mixture 1429:1449 The results showed that the xylanase enzyme has a major effect on the grain bran composition compared to cellulase and pectinase; however, a synergistic mixture yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually. 36673398 4 31 theme layers 662:667 arg1 degradation 634:644 selective degradation 624:644 selective degradation of the pericarp layers 624:667 Using carbohydrate degrading enzymes to hydrolyse the grain pericarp is a novel approach to biopolishing, where selective degradation of the pericarp layers occurs without adversely affecting the nutrient profile. 36673398 2 32 theme layers 408:413 arg1 removal 379:385 the removal 375:385 the removal of the outer fibrous layers 375:413 However, the utilisation of whole grain sorghum as an ingredient in conventional food formulations is limited due to its poor digestibility, which requires the removal of the outer fibrous layers. 36673398 9 33 theme water-soaked 1678:1689 arg1 samples 1691:1697 conventional water-soaked samples 1665:1697 conventional water-soaked samples 1665:1697 Compared to conventional water-soaked samples, grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase had visibly thinner and more degraded fibre layers. 36673398 7 34 from effect 1346:1351 arg1 composition 1371:1381 the grain bran composition 1356:1381 the grain bran composition 1356:1381 The results showed that the xylanase enzyme has a major effect on the grain bran composition compared to cellulase and pectinase; however, a synergistic mixture yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually. 36673398 4 35 theme pericarp 653:660 arg1 layers 662:667 the pericarp layers 649:667 the pericarp layers 649:667 Using carbohydrate degrading enzymes to hydrolyse the grain pericarp is a novel approach to biopolishing, where selective degradation of the pericarp layers occurs without adversely affecting the nutrient profile. 36673398 0 36 theme Synergistic 17:27 arg1 Cocktail 36:43 a Synergistic Enzyme Cocktail 15:43 a Synergistic Enzyme Cocktail 15:43 Formulation of a Synergistic Enzyme Cocktail for Controlled Degradation of Sorghum Grain Pericarp. 36673398 6 37 from sugars 1221:1226 arg1 extract 1244:1250 the pericarp extract 1231:1250 the pericarp extract 1231:1250 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 6 38 theme different 1123:1131 arg1 proportions 1133:1143 different proportions 1123:1143 different proportions for hydrolysing sorghum grain pericarp 1123:1182 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 5 39 theme due 837:839 arg1 enzymes 829:835 individual enzymes 818:835 individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme 818:1016 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 2 40 theme outer 394:398 arg1 layers 408:413 the outer fibrous layers 390:413 the outer fibrous layers 390:413 However, the utilisation of whole grain sorghum as an ingredient in conventional food formulations is limited due to its poor digestibility, which requires the removal of the outer fibrous layers. 36673398 6 41 theme sorghum 1161:1167 arg1 pericarp 1175:1182 hydrolysing sorghum grain pericarp 1149:1182 hydrolysing sorghum grain pericarp 1149:1182 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 5 42 theme individual 818:827 arg1 enzymes 829:835 individual enzymes 818:835 individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme 818:1016 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 1 43 theme grains 127:132 arg1 one 110:112 one 110:112 one 110:112 Sorghum is one of the major grains produced worldwide for food and fodder, owing to its nutritional profile advantages. 36673398 1 43 theme grains 127:132 arg1 grains 127:132 the major grains 117:132 the major grains produced worldwide for food and fodder 117:171 Sorghum is one of the major grains produced worldwide for food and fodder, owing to its nutritional profile advantages. 36673398 0 44 theme Cocktail 36:43 arg1 Formulation 0:10 Formulation 0:10 Formulation of a Synergistic Enzyme Cocktail for Controlled Degradation of Sorghum Grain Pericarp. 0:97 Formulation of a Synergistic Enzyme Cocktail for Controlled Degradation of Sorghum Grain Pericarp. 36673398 7 45 dep showed 1302:1307 arg1 yielded 1451:1457 yielded 1451:1457 yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually 1451:1559 The results showed that the xylanase enzyme has a major effect on the grain bran composition compared to cellulase and pectinase; however, a synergistic mixture yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually. 36673398 5 46 theme polysaccharides 879:893 arg1 presence 856:863 the complex presence 844:863 the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme 844:1016 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 3 47 theme Grain 416:420 arg1 breakage 422:429 Grain breakage 416:429 Grain breakage 416:429 Grain breakage and loss of essential nutrients also disadvantage traditional milling practices. 36673398 0 48 theme Enzyme 29:34 arg1 Cocktail 36:43 a Synergistic Enzyme Cocktail 15:43 a Synergistic Enzyme Cocktail 15:43 Formulation of a Synergistic Enzyme Cocktail for Controlled Degradation of Sorghum Grain Pericarp. 36673398 2 49 theme fibrous 400:406 arg1 layers 408:413 the outer fibrous layers 390:413 the outer fibrous layers 390:413 However, the utilisation of whole grain sorghum as an ingredient in conventional food formulations is limited due to its poor digestibility, which requires the removal of the outer fibrous layers. 36673398 5 50 theme complex 848:854 arg1 presence 856:863 the complex presence 844:863 the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme 844:1016 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 1 51 theme nutritional 187:197 arg1 profile 199:205 its nutritional profile 183:205 its nutritional profile advantages 183:216 Sorghum is one of the major grains produced worldwide for food and fodder, owing to its nutritional profile advantages. 36673398 0 52 theme Controlled 49:58 arg1 Degradation 60:70 Controlled Degradation 49:70 Controlled Degradation of Sorghum Grain Pericarp 49:96 Formulation of a Synergistic Enzyme Cocktail for Controlled Degradation of Sorghum Grain Pericarp. 36673398 9 53 theme pectinase 1776:1784 arg1 % 1774:1774 16.7% pectinase 1770:1784 16.7% pectinase 1770:1784 Compared to conventional water-soaked samples, grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase had visibly thinner and more degraded fibre layers. 36673398 6 54 theme present 1023:1029 arg1 study 1031:1035 The present study 1019:1035 The present study 1019:1035 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 6 55 theme specific 1212:1219 arg1 sugars 1221:1226 specific sugars 1212:1226 specific sugars in the pericarp extract 1212:1250 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 6 56 from cellulase 1095:1103 arg1 proportions 1133:1143 different proportions 1123:1143 different proportions for hydrolysing sorghum grain pericarp 1123:1182 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 3 57 theme nutrients 453:461 arg1 breakage 422:429 Grain breakage 416:429 Grain breakage 416:429 Grain breakage and loss of essential nutrients also disadvantage traditional milling practices. 36673398 3 57 theme nutrients 453:461 arg1 loss 435:438 loss 435:438 loss of essential nutrients 435:461 Grain breakage and loss of essential nutrients also disadvantage traditional milling practices. 36673398 4 58 theme degrading 531:539 arg1 enzymes 541:547 carbohydrate degrading enzymes 518:547 carbohydrate degrading enzymes 518:547 Using carbohydrate degrading enzymes to hydrolyse the grain pericarp is a novel approach to biopolishing, where selective degradation of the pericarp layers occurs without adversely affecting the nutrient profile. 36673398 2 59 dep grain 253:257 arg1 sorghum 259:265 sorghum 259:265 whole grain sorghum 247:265 However, the utilisation of whole grain sorghum as an ingredient in conventional food formulations is limited due to its poor digestibility, which requires the removal of the outer fibrous layers. 36673398 6 60 from pectinase 1110:1118 arg1 proportions 1133:1143 different proportions 1123:1143 different proportions for hydrolysing sorghum grain pericarp 1123:1182 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 8 61 theme soaked 1639:1644 arg1 grain 1646:1650 the soaked grain 1635:1650 the soaked grain 1635:1650 The results were confirmed by morphological and crystallinity studies of the soaked grain. 36673398 4 62 theme carbohydrate 518:529 arg1 enzymes 541:547 carbohydrate degrading enzymes 518:547 carbohydrate degrading enzymes 518:547 Using carbohydrate degrading enzymes to hydrolyse the grain pericarp is a novel approach to biopolishing, where selective degradation of the pericarp layers occurs without adversely affecting the nutrient profile. 36673398 9 63 theme conventional 1665:1676 arg1 samples 1691:1697 conventional water-soaked samples 1665:1697 conventional water-soaked samples 1665:1697 Compared to conventional water-soaked samples, grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase had visibly thinner and more degraded fibre layers. 36673398 6 64 theme sugars 1221:1226 arg1 yield 1203:1207 the yield 1199:1207 the yield of specific sugars in the pericarp extract 1199:1250 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 7 65 theme bran 1366:1369 arg1 composition 1371:1381 the grain bran composition 1356:1381 the grain bran composition 1356:1381 The results showed that the xylanase enzyme has a major effect on the grain bran composition compared to cellulase and pectinase; however, a synergistic mixture yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually. 36673398 7 66 contain has 1334:1336 arg1 enzyme 1327:1332 the xylanase enzyme 1314:1332 the xylanase enzyme 1314:1332 The results showed that the xylanase enzyme has a major effect on the grain bran composition compared to cellulase and pectinase; however, a synergistic mixture yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually. 36673398 7 66 contain has 1334:1336 arg2 effect 1346:1351 a major effect 1338:1351 a major effect on the grain bran composition 1338:1381 The results showed that the xylanase enzyme has a major effect on the grain bran composition compared to cellulase and pectinase; however, a synergistic mixture yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually. 36673398 5 67 theme specific 969:976 arg1 degradation 978:988 specific degradation 969:988 specific degradation 969:988 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 5 68 theme outer 910:914 arg1 layers 916:921 the grain's outer layers 898:921 the grain's outer layers 898:921 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 7 69 theme major 1340:1344 arg1 effect 1346:1351 a major effect 1338:1351 a major effect on the grain bran composition 1338:1381 The results showed that the xylanase enzyme has a major effect on the grain bran composition compared to cellulase and pectinase; however, a synergistic mixture yielded more hydrolysed sugars and anti-nutrients in the extract compared to each of the enzymes individually. 36673398 1 70 theme major 121:125 arg1 grains 127:132 the major grains 117:132 the major grains produced worldwide for food and fodder 117:171 Sorghum is one of the major grains produced worldwide for food and fodder, owing to its nutritional profile advantages. 36673398 9 71 theme fibre 1824:1828 arg1 layers 1830:1835 visibly thinner and more degraded fibre layers 1790:1835 visibly thinner and more degraded fibre layers 1790:1835 Compared to conventional water-soaked samples, grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase had visibly thinner and more degraded fibre layers. 36673398 4 72 theme novel 586:590 arg1 approach 592:599 a novel approach 584:599 a novel approach 584:599 Using carbohydrate degrading enzymes to hydrolyse the grain pericarp is a novel approach to biopolishing, where selective degradation of the pericarp layers occurs without adversely affecting the nutrient profile. 36673398 5 73 theme enzymes 752:758 arg1 synergism 739:747 A collective synergism 726:747 A collective synergism of enzymes 726:758 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 4 74 theme selective 624:632 arg1 degradation 634:644 selective degradation 624:644 selective degradation of the pericarp layers 624:667 Using carbohydrate degrading enzymes to hydrolyse the grain pericarp is a novel approach to biopolishing, where selective degradation of the pericarp layers occurs without adversely affecting the nutrient profile. 36673398 6 75 theme hydrolysing 1149:1159 arg1 pericarp 1175:1182 hydrolysing sorghum grain pericarp 1149:1182 hydrolysing sorghum grain pericarp 1149:1182 The present study aimed to formulate such an enzyme cocktail with xylanase, cellulase, and pectinase in different proportions for hydrolysing sorghum grain pericarp by determining the yield of specific sugars in the pericarp extract after a certain period of incubation. 36673398 2 76 theme poor 340:343 arg1 digestibility 345:357 its poor digestibility 336:357 its poor digestibility 336:357 However, the utilisation of whole grain sorghum as an ingredient in conventional food formulations is limited due to its poor digestibility, which requires the removal of the outer fibrous layers. 36673398 3 77 theme essential 443:451 arg1 nutrients 453:461 essential nutrients 443:461 essential nutrients 443:461 Grain breakage and loss of essential nutrients also disadvantage traditional milling practices. 36673398 8 78 theme morphological 1592:1604 arg1 studies 1624:1630 morphological and crystallinity studies 1592:1630 morphological and crystallinity studies of the soaked grain 1592:1650 The results were confirmed by morphological and crystallinity studies of the soaked grain. 36673398 5 79 theme effective 785:793 arg1 hydrolysis 795:804 effective hydrolysis 785:804 effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme 785:1016 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 36673398 9 80 contain had 1786:1788 arg1 grains 1700:1705 grains 1700:1705 grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase 1700:1784 Compared to conventional water-soaked samples, grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase had visibly thinner and more degraded fibre layers. 36673398 9 80 contain had 1786:1788 arg2 layers 1830:1835 visibly thinner and more degraded fibre layers 1790:1835 visibly thinner and more degraded fibre layers 1790:1835 Compared to conventional water-soaked samples, grains soaked in a cocktail with 66.7% xylanase, 16.7% cellulase, and 16.7% pectinase had visibly thinner and more degraded fibre layers. 36673398 2 81 from ingredient 273:282 arg1 formulations 305:316 conventional food formulations 287:316 conventional food formulations 287:316 However, the utilisation of whole grain sorghum as an ingredient in conventional food formulations is limited due to its poor digestibility, which requires the removal of the outer fibrous layers. 36673398 5 82 theme collective 728:737 arg1 synergism 739:747 A collective synergism 726:747 A collective synergism of enzymes 726:758 A collective synergism of enzymes has been proven to cause effective hydrolysis compared to individual enzymes due to the complex presence of non-starch polysaccharides in the grain's outer layers, which comprise a variety of sugars that show specific degradation with respect to each enzyme. 35863225 7 0 theme electrostatic 1238:1250 arg1 attraction 1252:1261 electrostatic attraction 1238:1261 electrostatic attraction 1238:1261 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 6 1 theme KEGG 905:908 arg1 analysis 910:917 KEGG analysis 905:917 KEGG analysis based on the genomic data 905:943 KEGG analysis based on the genomic data, and chemical composition analysis revealed that proteins and polysaccharides were the major components of metabolites. 35863225 7 2 theme three-dimensional 1120:1136 arg1 fluorescence 1138:1149 three-dimensional fluorescence 1120:1149 three-dimensional fluorescence 1120:1149 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 1 3 theme global 159:164 arg1 blooms 123:128 Algal blooms 117:128 Algal blooms caused by eutrophication 117:153 Algal blooms caused by eutrophication are global phenomena that seriously threaten the sustainable use of freshwater resources. 35863225 1 3 theme global 159:164 arg1 phenomena 166:174 global phenomena 159:174 global phenomena that seriously threaten the sustainable use of freshwater resources 159:242 Algal blooms caused by eutrophication are global phenomena that seriously threaten the sustainable use of freshwater resources. 35863225 5 4 theme flocculant 762:771 arg1 dosage 773:778 flocculant dosage 762:778 flocculant dosage 762:778 Accordingly, a flocculation efficiency of >95% was achieved when the fungus was cultured for six days, flocculant dosage was 11 g/L, rotation speed was 100 rpm, temperature was 25 °C, flocculation time was 5 h, and pH ranged between 4.0 and 9.0. 35863225 0 5 theme oryzae 82:87 arg1 pellets 59:65 fungal pellets 52:65 fungal pellets of Aspergillus oryzae 52:87 Bio-flocculation of Microcystis aeruginosa by using fungal pellets of Aspergillus oryzae: Performance and mechanism. 35863225 8 6 theme extracellular 1386:1398 arg1 proteins 1400:1407 extracellular proteins 1386:1407 extracellular proteins 1386:1407 Additionally, hyphal surface adsorption and chemisorption from extracellular proteins and exopolysaccharides aided in the removal of microalgae. 35863225 4 7 theme microalgae 631:640 arg1 parameters 576:585 crucial flocculation parameters 555:585 crucial flocculation parameters 555:585 Furthermore, it explored crucial flocculation parameters, adsorption kinetics, and thermodynamics of microalgae using A. oryzae. 35863225 4 7 theme microalgae 631:640 arg1 kinetics 599:606 adsorption kinetics 588:606 adsorption kinetics 588:606 Furthermore, it explored crucial flocculation parameters, adsorption kinetics, and thermodynamics of microalgae using A. oryzae. 35863225 4 7 theme microalgae 631:640 arg1 thermodynamics 613:626 thermodynamics 613:626 thermodynamics of microalgae 613:640 Furthermore, it explored crucial flocculation parameters, adsorption kinetics, and thermodynamics of microalgae using A. oryzae. 35863225 5 8 theme % 704:704 arg1 efficiency 687:696 a flocculation efficiency 672:696 a flocculation efficiency of >95% 672:704 Accordingly, a flocculation efficiency of >95% was achieved when the fungus was cultured for six days, flocculant dosage was 11 g/L, rotation speed was 100 rpm, temperature was 25 °C, flocculation time was 5 h, and pH ranged between 4.0 and 9.0. 35863225 2 9 theme high 307:310 arg1 levels 312:317 high levels 307:317 high levels of residue 307:328 Traditional water treatment chemicals often typically lead to high levels of residue and cause damage to the morphology of algal cells. 35863225 6 10 theme composition 959:969 arg1 analysis 971:978 chemical composition analysis 950:978 chemical composition analysis 950:978 KEGG analysis based on the genomic data, and chemical composition analysis revealed that proteins and polysaccharides were the major components of metabolites. 35863225 7 11 theme electrostatic 1199:1211 arg1 spectroscopy 1185:1196 infrared spectroscopy 1176:1196 infrared spectroscopy 1176:1196 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 7 11 theme electrostatic 1199:1211 arg1 attraction 1213:1222 electrostatic attraction 1199:1222 electrostatic attraction 1199:1222 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 8 12 theme surface 1344:1350 arg1 adsorption 1352:1361 hyphal surface adsorption 1337:1361 hyphal surface adsorption 1337:1361 Additionally, hyphal surface adsorption and chemisorption from extracellular proteins and exopolysaccharides aided in the removal of microalgae. 35863225 7 13 theme scanning 1090:1097 arg1 microscopy 1108:1117 scanning electron microscopy 1090:1117 scanning electron microscopy 1090:1117 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 9 14 theme simple 1552:1557 arg1 manner 1588:1593 a simple, effective, and eco-friendly manner 1550:1593 a simple, effective, and eco-friendly manner 1550:1593 Therefore, fungi-based bio-flocculants have the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites. 35863225 9 15 theme metabolites 1643:1653 arg1 extraction 1615:1624 the complex extraction 1603:1624 the complex extraction of extracellular metabolites 1603:1653 Therefore, fungi-based bio-flocculants have the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites. 35863225 3 16 theme fungal 421:426 arg1 bio-flocculant 428:441 an eco-friendly fungal bio-flocculant 405:441 an eco-friendly fungal bio-flocculant 405:441 This study investigated an eco-friendly fungal bio-flocculant, Aspergillus oryzae, to remove the representative microalgae (Microcystis aeruginosa). 35863225 3 16 theme fungal 421:426 arg1 oryzae 456:461 Aspergillus oryzae 444:461 Aspergillus oryzae 444:461 This study investigated an eco-friendly fungal bio-flocculant, Aspergillus oryzae, to remove the representative microalgae (Microcystis aeruginosa). 35863225 7 17 theme electron 1099:1106 arg1 microscopy 1108:1117 scanning electron microscopy 1090:1117 scanning electron microscopy 1090:1117 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 8 18 from proteins 1400:1407 arg1 adsorption 1352:1361 hyphal surface adsorption 1337:1361 hyphal surface adsorption 1337:1361 Additionally, hyphal surface adsorption and chemisorption from extracellular proteins and exopolysaccharides aided in the removal of microalgae. 35863225 8 18 from proteins 1400:1407 arg1 chemisorption 1367:1379 chemisorption 1367:1379 chemisorption 1367:1379 Additionally, hyphal surface adsorption and chemisorption from extracellular proteins and exopolysaccharides aided in the removal of microalgae. 35863225 9 19 theme complex 1607:1613 arg1 extraction 1615:1624 the complex extraction 1603:1624 the complex extraction of extracellular metabolites 1603:1653 Therefore, fungi-based bio-flocculants have the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites. 35863225 6 20 theme chemical 950:957 arg1 analysis 971:978 chemical composition analysis 950:978 chemical composition analysis 950:978 KEGG analysis based on the genomic data, and chemical composition analysis revealed that proteins and polysaccharides were the major components of metabolites. 35863225 7 21 dep destabilization 1276:1290 arg1 the 1272:1274 the 1272:1274 the 1272:1274 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 4 22 theme adsorption 588:597 arg1 kinetics 599:606 adsorption kinetics 588:606 adsorption kinetics 588:606 Furthermore, it explored crucial flocculation parameters, adsorption kinetics, and thermodynamics of microalgae using A. oryzae. 35863225 2 23 theme treatment 263:271 arg1 chemicals 273:281 Traditional water treatment chemicals 245:281 Traditional water treatment chemicals 245:281 Traditional water treatment chemicals often typically lead to high levels of residue and cause damage to the morphology of algal cells. 35863225 9 24 contain have 1507:1510 arg2 potential 1516:1524 the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites 1512:1653 the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites 1512:1653 Therefore, fungi-based bio-flocculants have the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites. 35863225 9 24 contain have 1507:1510 arg1 bio-flocculants 1491:1505 fungi-based bio-flocculants 1479:1505 fungi-based bio-flocculants 1479:1505 Therefore, fungi-based bio-flocculants have the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites. 35863225 6 25 theme metabolites 1052:1062 arg1 components 1038:1047 the major components 1028:1047 the major components of metabolites 1028:1062 KEGG analysis based on the genomic data, and chemical composition analysis revealed that proteins and polysaccharides were the major components of metabolites. 35863225 6 25 theme metabolites 1052:1062 arg1 polysaccharides 1007:1021 polysaccharides 1007:1021 polysaccharides 1007:1021 KEGG analysis based on the genomic data, and chemical composition analysis revealed that proteins and polysaccharides were the major components of metabolites. 35863225 6 25 theme metabolites 1052:1062 arg1 proteins 994:1001 proteins 994:1001 proteins 994:1001 KEGG analysis based on the genomic data, and chemical composition analysis revealed that proteins and polysaccharides were the major components of metabolites. 35863225 0 26 theme aeruginosa 32:41 arg1 Bio-flocculation 0:15 Bio-flocculation 0:15 Bio-flocculation of Microcystis aeruginosa by using fungal pellets of Aspergillus oryzae: Performance and mechanism. 0:115 Bio-flocculation of Microcystis aeruginosa by using fungal pellets of Aspergillus oryzae: Performance and mechanism. 35863225 7 27 theme Zeta 1065:1068 arg1 analysis 1080:1087 Zeta potential analysis 1065:1087 Zeta potential analysis 1065:1087 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 2 28 theme residue 322:328 arg1 levels 312:317 high levels 307:317 high levels of residue 307:328 Traditional water treatment chemicals often typically lead to high levels of residue and cause damage to the morphology of algal cells. 35863225 3 29 theme representative 478:491 arg1 microalgae 493:502 the representative microalgae 474:502 the representative microalgae (Microcystis aeruginosa) 474:527 This study investigated an eco-friendly fungal bio-flocculant, Aspergillus oryzae, to remove the representative microalgae (Microcystis aeruginosa). 35863225 7 30 theme infrared 1176:1183 arg1 spectroscopy 1185:1196 infrared spectroscopy 1176:1196 infrared spectroscopy 1176:1196 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 7 30 theme infrared 1176:1183 arg1 attraction 1213:1222 electrostatic attraction 1199:1222 electrostatic attraction 1199:1222 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 7 31 theme potential 1070:1078 arg1 analysis 1080:1087 Zeta potential analysis 1065:1087 Zeta potential analysis 1065:1087 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 5 32 theme flocculation 843:854 arg1 time 856:859 flocculation time 843:859 flocculation time 843:859 Accordingly, a flocculation efficiency of >95% was achieved when the fungus was cultured for six days, flocculant dosage was 11 g/L, rotation speed was 100 rpm, temperature was 25 °C, flocculation time was 5 h, and pH ranged between 4.0 and 9.0. 35863225 8 33 theme hyphal 1337:1342 arg1 adsorption 1352:1361 hyphal surface adsorption 1337:1361 hyphal surface adsorption 1337:1361 Additionally, hyphal surface adsorption and chemisorption from extracellular proteins and exopolysaccharides aided in the removal of microalgae. 35863225 2 34 theme water 257:261 arg1 chemicals 273:281 Traditional water treatment chemicals 245:281 Traditional water treatment chemicals 245:281 Traditional water treatment chemicals often typically lead to high levels of residue and cause damage to the morphology of algal cells. 35863225 6 35 theme major 1032:1036 arg1 components 1038:1047 the major components 1028:1047 the major components of metabolites 1028:1062 KEGG analysis based on the genomic data, and chemical composition analysis revealed that proteins and polysaccharides were the major components of metabolites. 35863225 6 35 theme major 1032:1036 arg1 polysaccharides 1007:1021 polysaccharides 1007:1021 polysaccharides 1007:1021 KEGG analysis based on the genomic data, and chemical composition analysis revealed that proteins and polysaccharides were the major components of metabolites. 35863225 6 35 theme major 1032:1036 arg1 proteins 994:1001 proteins 994:1001 proteins 994:1001 KEGG analysis based on the genomic data, and chemical composition analysis revealed that proteins and polysaccharides were the major components of metabolites. 35863225 4 36 theme crucial 555:561 arg1 parameters 576:585 crucial flocculation parameters 555:585 crucial flocculation parameters 555:585 Furthermore, it explored crucial flocculation parameters, adsorption kinetics, and thermodynamics of microalgae using A. oryzae. 35863225 2 37 theme Traditional 245:255 arg1 chemicals 273:281 Traditional water treatment chemicals 245:281 Traditional water treatment chemicals 245:281 Traditional water treatment chemicals often typically lead to high levels of residue and cause damage to the morphology of algal cells. 35863225 1 38 theme freshwater 223:232 arg1 resources 234:242 freshwater resources 223:242 freshwater resources 223:242 Algal blooms caused by eutrophication are global phenomena that seriously threaten the sustainable use of freshwater resources. 35863225 3 39 theme eco-friendly 408:419 arg1 bio-flocculant 428:441 an eco-friendly fungal bio-flocculant 405:441 an eco-friendly fungal bio-flocculant 405:441 This study investigated an eco-friendly fungal bio-flocculant, Aspergillus oryzae, to remove the representative microalgae (Microcystis aeruginosa). 35863225 3 39 theme eco-friendly 408:419 arg1 oryzae 456:461 Aspergillus oryzae 444:461 Aspergillus oryzae 444:461 This study investigated an eco-friendly fungal bio-flocculant, Aspergillus oryzae, to remove the representative microalgae (Microcystis aeruginosa). 35863225 6 40 theme genomic 932:938 arg1 data 940:943 the genomic data 928:943 the genomic data 928:943 KEGG analysis based on the genomic data, and chemical composition analysis revealed that proteins and polysaccharides were the major components of metabolites. 35863225 0 41 dep Bio-flocculation 0:15 arg1 mechanism 106:114 mechanism 106:114 mechanism 106:114 Bio-flocculation of Microcystis aeruginosa by using fungal pellets of Aspergillus oryzae: Performance and mechanism. 35863225 0 41 dep Bio-flocculation 0:15 arg1 Performance 90:100 Performance 90:100 Performance 90:100 Bio-flocculation of Microcystis aeruginosa by using fungal pellets of Aspergillus oryzae: Performance and mechanism. 35863225 1 42 theme Algal 117:121 arg1 blooms 123:128 Algal blooms 117:128 Algal blooms caused by eutrophication 117:153 Algal blooms caused by eutrophication are global phenomena that seriously threaten the sustainable use of freshwater resources. 35863225 1 42 theme Algal 117:121 arg1 phenomena 166:174 global phenomena 159:174 global phenomena that seriously threaten the sustainable use of freshwater resources 159:242 Algal blooms caused by eutrophication are global phenomena that seriously threaten the sustainable use of freshwater resources. 35863225 0 43 theme fungal 52:57 arg1 pellets 59:65 fungal pellets 52:65 fungal pellets of Aspergillus oryzae 52:87 Bio-flocculation of Microcystis aeruginosa by using fungal pellets of Aspergillus oryzae: Performance and mechanism. 35863225 5 44 theme flocculation 674:685 arg1 efficiency 687:696 a flocculation efficiency 672:696 a flocculation efficiency of >95% 672:704 Accordingly, a flocculation efficiency of >95% was achieved when the fungus was cultured for six days, flocculant dosage was 11 g/L, rotation speed was 100 rpm, temperature was 25 °C, flocculation time was 5 h, and pH ranged between 4.0 and 9.0. 35863225 4 45 theme flocculation 563:574 arg1 parameters 576:585 crucial flocculation parameters 555:585 crucial flocculation parameters 555:585 Furthermore, it explored crucial flocculation parameters, adsorption kinetics, and thermodynamics of microalgae using A. oryzae. 35863225 7 46 theme X-ray 1152:1156 arg1 spectroscopy 1158:1169 X-ray spectroscopy 1152:1169 X-ray spectroscopy 1152:1169 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 7 47 theme microalgae 1311:1320 arg1 aggregation 1296:1306 aggregation 1296:1306 aggregation 1296:1306 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 7 47 theme microalgae 1311:1320 arg1 destabilization 1276:1290 destabilization 1276:1290 destabilization 1276:1290 Zeta potential analysis, scanning electron microscopy, three-dimensional fluorescence, X-ray spectroscopy, and infrared spectroscopy, electrostatic attraction revealed that electrostatic attraction promoted the destabilization and aggregation of microalgae. 35863225 8 48 theme microalgae 1456:1465 arg1 removal 1445:1451 the removal 1441:1451 the removal of microalgae 1441:1465 Additionally, hyphal surface adsorption and chemisorption from extracellular proteins and exopolysaccharides aided in the removal of microalgae. 35863225 1 49 theme resources 234:242 arg1 use 216:218 the sustainable use 200:218 the sustainable use of freshwater resources 200:242 Algal blooms caused by eutrophication are global phenomena that seriously threaten the sustainable use of freshwater resources. 35863225 8 50 from exopolysaccharides 1413:1430 arg1 adsorption 1352:1361 hyphal surface adsorption 1337:1361 hyphal surface adsorption 1337:1361 Additionally, hyphal surface adsorption and chemisorption from extracellular proteins and exopolysaccharides aided in the removal of microalgae. 35863225 8 50 from exopolysaccharides 1413:1430 arg1 chemisorption 1367:1379 chemisorption 1367:1379 chemisorption 1367:1379 Additionally, hyphal surface adsorption and chemisorption from extracellular proteins and exopolysaccharides aided in the removal of microalgae. 35863225 9 51 theme eco-friendly 1575:1586 arg1 manner 1588:1593 a simple, effective, and eco-friendly manner 1550:1593 a simple, effective, and eco-friendly manner 1550:1593 Therefore, fungi-based bio-flocculants have the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites. 35863225 0 52 theme Aspergillus 70:80 arg1 oryzae 82:87 Aspergillus oryzae 70:87 Aspergillus oryzae 70:87 Bio-flocculation of Microcystis aeruginosa by using fungal pellets of Aspergillus oryzae: Performance and mechanism. 35863225 9 53 theme effective 1560:1568 arg1 manner 1588:1593 a simple, effective, and eco-friendly manner 1550:1593 a simple, effective, and eco-friendly manner 1550:1593 Therefore, fungi-based bio-flocculants have the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites. 35863225 1 54 theme sustainable 204:214 arg1 use 216:218 the sustainable use 200:218 the sustainable use of freshwater resources 200:242 Algal blooms caused by eutrophication are global phenomena that seriously threaten the sustainable use of freshwater resources. 35863225 2 55 theme algal 368:372 arg1 cells 374:378 algal cells 368:378 algal cells 368:378 Traditional water treatment chemicals often typically lead to high levels of residue and cause damage to the morphology of algal cells. 35863225 9 56 theme extracellular 1629:1641 arg1 metabolites 1643:1653 extracellular metabolites 1629:1653 extracellular metabolites 1629:1653 Therefore, fungi-based bio-flocculants have the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites. 35863225 3 57 dep microalgae 493:502 arg1 aeruginosa 517:526 Microcystis aeruginosa 505:526 Microcystis aeruginosa 505:526 This study investigated an eco-friendly fungal bio-flocculant, Aspergillus oryzae, to remove the representative microalgae (Microcystis aeruginosa). 35863225 2 58 theme cells 374:378 arg1 morphology 354:363 the morphology 350:363 the morphology of algal cells 350:378 Traditional water treatment chemicals often typically lead to high levels of residue and cause damage to the morphology of algal cells. 35863225 9 59 theme fungi-based 1479:1489 arg1 bio-flocculants 1491:1505 fungi-based bio-flocculants 1479:1505 fungi-based bio-flocculants 1479:1505 Therefore, fungi-based bio-flocculants have the potential to remove microalgae in a simple, effective, and eco-friendly manner without the complex extraction of extracellular metabolites. 35856073 3 0 from flaccidum 430:438 arg1 tool 467:470 a powerful biocatalytic tool 443:470 a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro 443:575 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 3 0 from flaccidum 430:438 arg1 synthase 380:387 xylan synthase 1 374:389 xylan synthase 1 from the charophyte alga Klebsormidium flaccidum 374:438 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 1 1 theme cell 163:166 arg1 walls 168:172 the cell walls 159:172 the cell walls of nearly all flowering plants 159:203 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 5 2 theme surface 956:962 arg1 functionalization 964:980 bottom-up and surface functionalization 942:980 functionalization 964:980 Furthermore, we highlight two approaches for bottom-up and surface functionalization of xylan microparticles with chemical probes and explore the susceptibility of xylan microparticles to enzymatic hydrolysis. 35856073 5 3 theme microparticles 1067:1080 arg1 susceptibility 1043:1056 the susceptibility 1039:1056 the susceptibility of xylan microparticles to enzymatic hydrolysis 1039:1104 Furthermore, we highlight two approaches for bottom-up and surface functionalization of xylan microparticles with chemical probes and explore the susceptibility of xylan microparticles to enzymatic hydrolysis. 35856073 4 4 theme polymer 877:883 arg1 elongation 885:894 polymer elongation 877:894 polymer elongation 877:894 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 2 5 theme synthesis 300:308 arg1 studies 283:289 studies 283:289 studies of their synthesis and structure-function relationships 283:345 Unfortunately, naturally occurring xylans are highly heterogeneous, limiting studies of their synthesis and structure-function relationships. 35856073 6 6 theme wall 1225:1228 arg1 biosynthesis 1230:1241 cell wall biosynthesis 1220:1241 cell wall biosynthesis 1220:1241 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 4 7 theme saccharide 636:645 arg1 primers 647:653 defined saccharide primers 628:653 defined saccharide primers as substrates 628:667 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 6 8 theme polymer-polymer 1247:1261 arg1 interactions 1263:1274 polymer-polymer interactions 1247:1274 polymer-polymer interactions 1247:1274 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 6 9 theme new 1307:1309 arg1 materials 1320:1328 new biobased materials 1307:1328 new biobased materials with favorable properties for biomedical and renewable applications 1307:1396 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 6 10 theme functional 1176:1185 arg1 studies 1187:1193 structural and functional studies 1161:1193 structural and functional studies of xylans 1161:1203 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 4 11 theme microparticles 758:771 arg1 composition 701:711 composition 701:711 composition 701:711 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 4 11 theme microparticles 758:771 arg1 properties 718:727 properties 718:727 properties 718:727 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 4 11 theme microparticles 758:771 arg1 shape 694:698 shape 694:698 shape 694:698 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 1 12 theme polysaccharides 117:131 arg1 family 92:97 a diverse family 82:97 a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants 82:203 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 1 12 theme polysaccharides 117:131 arg1 Xylans 71:76 Xylans 71:76 Xylans 71:76 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 6 13 theme renewable 1375:1383 arg1 applications 1385:1396 biomedical and renewable applications 1360:1396 biomedical and renewable applications 1360:1396 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 6 14 theme structural 1161:1170 arg1 studies 1187:1193 structural and functional studies 1161:1193 structural and functional studies of xylans 1161:1203 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 3 15 theme xylan 374:378 arg1 tool 467:470 a powerful biocatalytic tool 443:470 a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro 443:575 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 3 15 theme xylan 374:378 arg1 synthase 380:387 xylan synthase 1 374:389 xylan synthase 1 from the charophyte alga Klebsormidium flaccidum 374:438 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 0 16 theme Enzymatic 0:8 arg1 Synthesis 10:18 Enzymatic Synthesis 0:18 Enzymatic Synthesis of Xylan 0:27 Enzymatic Synthesis of Xylan Microparticles with Tunable Morphologies. 35856073 3 17 theme charophyte 400:409 arg1 flaccidum 430:438 the charophyte alga Klebsormidium flaccidum 396:438 the charophyte alga Klebsormidium flaccidum 396:438 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 6 18 theme biomedical 1360:1369 arg1 applications 1385:1396 biomedical and renewable applications 1360:1396 biomedical and renewable applications 1360:1396 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 1 19 theme diverse 84:90 arg1 family 92:97 a diverse family 82:97 a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants 82:203 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 1 19 theme diverse 84:90 arg1 Xylans 71:76 Xylans 71:76 Xylans 71:76 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 3 20 theme powerful 445:452 arg1 tool 467:470 a powerful biocatalytic tool 443:470 a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro 443:575 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 3 20 theme powerful 445:452 arg1 synthase 380:387 xylan synthase 1 374:389 xylan synthase 1 from the charophyte alga Klebsormidium flaccidum 374:438 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 3 21 theme alga 411:414 arg1 flaccidum 430:438 the charophyte alga Klebsormidium flaccidum 396:438 the charophyte alga Klebsormidium flaccidum 396:438 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 2 22 theme relationships 333:345 arg1 studies 283:289 studies 283:289 studies of their synthesis and structure-function relationships 283:345 Unfortunately, naturally occurring xylans are highly heterogeneous, limiting studies of their synthesis and structure-function relationships. 35856073 1 23 theme flowering 188:196 arg1 plants 198:203 nearly all flowering plants 177:203 nearly all flowering plants 177:203 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 0 24 theme Xylan 23:27 arg1 Synthesis 10:18 Enzymatic Synthesis 0:18 Enzymatic Synthesis of Xylan 0:27 Enzymatic Synthesis of Xylan Microparticles with Tunable Morphologies. 35856073 4 25 theme uridine 584:590 arg1 diphosphate-xylose 592:609 uridine diphosphate-xylose 584:609 uridine diphosphate-xylose (UDP-xylose) 584:622 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 4 25 theme uridine 584:590 arg1 UDP-xylose 612:621 UDP-xylose 612:621 UDP-xylose 612:621 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 5 26 theme microparticles 991:1004 arg1 functionalization 964:980 bottom-up and surface functionalization 942:980 functionalization 964:980 Furthermore, we highlight two approaches for bottom-up and surface functionalization of xylan microparticles with chemical probes and explore the susceptibility of xylan microparticles to enzymatic hydrolysis. 35856073 2 27 theme structure-function 314:331 arg1 relationships 333:345 structure-function relationships 314:345 structure-function relationships 314:345 Unfortunately, naturally occurring xylans are highly heterogeneous, limiting studies of their synthesis and structure-function relationships. 35856073 1 28 theme plants 198:203 arg1 walls 168:172 the cell walls 159:172 the cell walls of nearly all flowering plants 159:203 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 5 29 theme chemical 1011:1018 arg1 probes 1020:1025 chemical probes 1011:1025 chemical probes 1011:1025 Furthermore, we highlight two approaches for bottom-up and surface functionalization of xylan microparticles with chemical probes and explore the susceptibility of xylan microparticles to enzymatic hydrolysis. 35856073 6 30 theme possible 1288:1295 arg1 routes 1297:1302 possible routes 1288:1302 possible routes to new biobased materials with favorable properties for biomedical and renewable applications 1288:1396 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 1 31 theme hemicellulosic 102:115 arg1 polysaccharides 117:131 hemicellulosic polysaccharides 102:131 hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants 102:203 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 4 32 theme self-assembling 736:750 arg1 microparticles 758:771 the self-assembling xylan microparticles 732:771 the self-assembling xylan microparticles 732:771 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 5 33 theme enzymatic 1085:1093 arg1 hydrolysis 1095:1104 enzymatic hydrolysis 1085:1104 enzymatic hydrolysis 1085:1104 Furthermore, we highlight two approaches for bottom-up and surface functionalization of xylan microparticles with chemical probes and explore the susceptibility of xylan microparticles to enzymatic hydrolysis. 35856073 3 34 theme biocatalytic 454:465 arg1 tool 467:470 a powerful biocatalytic tool 443:470 a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro 443:575 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 3 34 theme biocatalytic 454:465 arg1 synthase 380:387 xylan synthase 1 374:389 xylan synthase 1 from the charophyte alga Klebsormidium flaccidum 374:438 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 6 35 with materials 1320:1328 arg1 properties 1345:1354 favorable properties 1335:1354 favorable properties for biomedical and renewable applications 1335:1396 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 6 36 theme favorable 1335:1343 arg1 properties 1345:1354 favorable properties 1335:1354 favorable properties for biomedical and renewable applications 1335:1396 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 3 37 theme bottom-up 480:488 arg1 synthesis 490:498 the bottom-up synthesis 476:498 the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro 476:575 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 3 38 theme Klebsormidium 416:428 arg1 flaccidum 430:438 the charophyte alga Klebsormidium flaccidum 396:438 the charophyte alga Klebsormidium flaccidum 396:438 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 2 39 theme occurring 231:239 arg1 xylans 241:246 naturally occurring xylans 221:246 naturally occurring xylans 221:246 Unfortunately, naturally occurring xylans are highly heterogeneous, limiting studies of their synthesis and structure-function relationships. 35856073 3 40 theme xylan 514:518 arg1 polymers 520:527 pure β-1,4 xylan polymers 503:527 pure β-1,4 xylan polymers that self-assemble into microparticles in vitro 503:575 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 0 41 theme Tunable 49:55 arg1 Morphologies 57:68 Tunable Morphologies 49:68 Tunable Morphologies 49:68 Enzymatic Synthesis of Xylan Microparticles with Tunable Morphologies. 35856073 6 42 theme useful 1141:1146 arg1 platform 1148:1155 a useful platform 1139:1155 a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions 1139:1274 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 3 43 theme polymers 520:527 arg1 synthesis 490:498 the bottom-up synthesis 476:498 the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro 476:575 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 4 44 dep shape 694:698 arg1 the 690:692 the 690:692 the 690:692 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 4 45 theme xylan 752:756 arg1 microparticles 758:771 the self-assembling xylan microparticles 732:771 the self-assembling xylan microparticles 732:771 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 5 46 theme xylan 1061:1065 arg1 microparticles 1067:1080 xylan microparticles 1061:1080 xylan microparticles 1061:1080 Furthermore, we highlight two approaches for bottom-up and surface functionalization of xylan microparticles with chemical probes and explore the susceptibility of xylan microparticles to enzymatic hydrolysis. 35856073 4 47 theme xylan 831:835 arg1 primer 853:858 the xylan oligosaccharide primer 827:858 the xylan oligosaccharide primer used to initiate polymer elongation 827:894 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 3 48 theme pure 503:506 arg1 polymers 520:527 pure β-1,4 xylan polymers 503:527 pure β-1,4 xylan polymers that self-assemble into microparticles in vitro 503:575 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 6 49 theme xylans 1198:1203 arg1 studies 1187:1193 structural and functional studies 1161:1193 structural and functional studies of xylans 1161:1203 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 6 50 theme biobased 1311:1318 arg1 materials 1320:1328 new biobased materials 1307:1328 new biobased materials with favorable properties for biomedical and renewable applications 1307:1396 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 4 51 theme fine 809:812 arg1 structure 814:822 the fine structure 805:822 the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation 805:894 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 3 52 theme β-1,4 508:512 arg1 polymers 520:527 pure β-1,4 xylan polymers 503:527 pure β-1,4 xylan polymers that self-assemble into microparticles in vitro 503:575 Here, we demonstrate that xylan synthase 1 from the charophyte alga Klebsormidium flaccidum is a powerful biocatalytic tool for the bottom-up synthesis of pure β-1,4 xylan polymers that self-assemble into microparticles in vitro. 35856073 6 53 theme cell 1220:1223 arg1 biosynthesis 1230:1241 cell wall biosynthesis 1220:1241 cell wall biosynthesis 1220:1241 Together, these results provide a useful platform for structural and functional studies of xylans to investigate cell wall biosynthesis and polymer-polymer interactions and suggest possible routes to new biobased materials with favorable properties for biomedical and renewable applications. 35856073 5 54 theme xylan 985:989 arg1 microparticles 991:1004 xylan microparticles 985:1004 xylan microparticles 985:1004 Furthermore, we highlight two approaches for bottom-up and surface functionalization of xylan microparticles with chemical probes and explore the susceptibility of xylan microparticles to enzymatic hydrolysis. 35856073 4 55 theme primer 853:858 arg1 structure 814:822 the fine structure 805:822 the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation 805:894 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 4 56 theme defined 628:634 arg1 primers 647:653 defined saccharide primers 628:653 defined saccharide primers as substrates 628:667 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 1 57 located found 133:137 arg2 polysaccharides 117:131 hemicellulosic polysaccharides 102:131 hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants 102:203 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 1 57 located found 133:137 arg1 abundance 142:150 abundance 142:150 abundance 142:150 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 1 57 located found 133:137 arg1 walls 168:172 the cell walls 159:172 the cell walls of nearly all flowering plants 159:203 Xylans are a diverse family of hemicellulosic polysaccharides found in abundance within the cell walls of nearly all flowering plants. 35856073 4 58 theme oligosaccharide 837:851 arg1 primer 853:858 the xylan oligosaccharide primer 827:858 the xylan oligosaccharide primer used to initiate polymer elongation 827:894 Using uridine diphosphate-xylose (UDP-xylose) and defined saccharide primers as substrates, we demonstrate that the shape, composition, and properties of the self-assembling xylan microparticles could be readily controlled via the fine structure of the xylan oligosaccharide primer used to initiate polymer elongation. 35856073 5 59 theme bottom-up 942:950 arg1 functionalization 964:980 bottom-up and surface functionalization 942:980 functionalization 964:980 Furthermore, we highlight two approaches for bottom-up and surface functionalization of xylan microparticles with chemical probes and explore the susceptibility of xylan microparticles to enzymatic hydrolysis. 36394313 6 0 gly fucosylate 1377:1386 arg1 peptides 1388:1395 peptides 1388:1395 peptides 1388:1395 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 10 1 theme LPG2 2541:2544 arg1 deletion 2496:2503 deletion 2496:2503 deletion of the Golgi nucleotide transporter LPG2 2496:2544 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 11 2 theme rare 2609:2612 arg1 mutant 2614:2619 a rare mutant 2607:2619 a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 2607:2678 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 9 3 theme therapeutic 2333:2343 arg1 intervention 2345:2356 therapeutic intervention 2333:2356 therapeutic intervention 2333:2356 This work advances knowledge of the experimental proteome by nearly 2-fold, to more than 6,500 proteins and thus provides a great resource to investigators seeking to decode how this parasite is transmitted and causes disease and to identify new targets for therapeutic intervention. 36394313 0 4 theme Mitochondrial 177:189 arg1 FUT1 210:213 the Mitochondrial Fucosyltransferase FUT1 173:213 the Mitochondrial Fucosyltransferase FUT1 173:213 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 3 5 theme virulence-associated 572:591 arg1 genes 593:597 two virulence-associated genes 568:597 two virulence-associated genes 568:597 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 8 6 theme trypanosomatid 1916:1929 arg1 IMPORTANCE 1878:1887 IMPORTANCE Leishmania 1878:1898 IMPORTANCE Leishmania 1878:1898 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 6 theme trypanosomatid 1916:1929 arg1 humans 1953:1958 humans 1953:1958 humans 1953:1958 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 6 theme trypanosomatid 1916:1929 arg1 parasite 1941:1948 a widespread trypanosomatid protozoan parasite 1903:1948 a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected 1903:2072 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 12 7 theme vital 2846:2850 arg1 s 2877:2877 this vital protein's elusive target(s) 2841:2878 this vital protein's elusive target(s) 2841:2878 This suggests that this vital protein's elusive target(s) may be more complex than the methods used could detect or that this target may not be a protein but perhaps another glycoconjugate or glycolipid. 36394313 10 8 theme nucleotide 2518:2527 arg1 LPG2 2541:2544 the Golgi nucleotide transporter LPG2 2508:2544 the Golgi nucleotide transporter LPG2 2508:2544 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 9 9 theme proteome 2124:2131 arg1 knowledge 2094:2102 knowledge 2094:2102 knowledge of the experimental proteome 2094:2131 This work advances knowledge of the experimental proteome by nearly 2-fold, to more than 6,500 proteins and thus provides a great resource to investigators seeking to decode how this parasite is transmitted and causes disease and to identify new targets for therapeutic intervention. 36394313 4 10 with approaches 822:831 arg1 ETD 919:921 ETD 919:921 ETD 919:921 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 4 10 with approaches 822:831 arg1 dissociation 905:916 electron transfer dissociation 887:916 electron transfer dissociation (ETD) 887:922 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 4 10 with approaches 822:831 arg1 HCD 878:880 HCD 878:880 HCD 878:880 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 4 10 with approaches 822:831 arg1 dissociation 864:875 higher-energy collisional dissociation 838:875 higher-energy collisional dissociation (HCD) 838:881 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 0 11 theme FUT1 210:213 arg1 Mutants 93:99 Null Mutants 88:99 Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1 88:213 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 3 12 from genes 593:597 arg1 Leishmania 602:611 Leishmania 602:611 Leishmania 602:611 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 11 13 gly fucosylation 2776:2787 arg1 N-glycans 2811:2819 N-glycans 2811:2819 N-glycans 2811:2819 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 11 13 gly fucosylation 2776:2787 arg1 peptides 2799:2806 peptides 2799:2806 peptides 2799:2806 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 4 14 theme peptide 760:766 arg1 fractionation 768:780 deep peptide fractionation 755:780 deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) 755:922 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 8 15 theme humans 1953:1958 arg1 IMPORTANCE 1878:1887 IMPORTANCE Leishmania 1878:1898 IMPORTANCE Leishmania 1878:1898 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 15 theme humans 1953:1958 arg1 humans 1953:1958 humans 1953:1958 humans 1953:1958 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 15 theme humans 1953:1958 arg1 parasite 1941:1948 a widespread trypanosomatid protozoan parasite 1903:1948 a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected 1903:2072 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 7 16 theme critical 1663:1670 arg1 resource 1672:1679 a critical resource 1661:1679 a critical resource for the community on the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics 1661:1875 This work provides a critical resource for the community on the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics. 36394313 6 17 theme protein 1423:1429 arg1 fucosylation 1431:1442 protein fucosylation 1423:1442 protein fucosylation 1423:1442 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 3 18 from understanding 551:563 arg1 Leishmania 602:611 Leishmania 602:611 Leishmania 602:611 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 6 19 theme ultradeep 1470:1478 arg1 analysis 1480:1487 our ultradeep analysis 1466:1487 our ultradeep analysis 1466:1487 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 7 20 theme future 1857:1862 arg1 therapeutics 1864:1875 future therapeutics 1857:1875 future therapeutics 1857:1875 This work provides a critical resource for the community on the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics. 36394313 10 21 theme ultradeep 2363:2371 arg1 approach 2384:2391 The ultradeep proteomics approach 2359:2391 The ultradeep proteomics approach 2359:2391 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 3 22 theme mannose/arabinopyranose/fucose 633:662 arg1 LPG2 694:697 LPG2 694:697 LPG2 694:697 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 3 22 theme mannose/arabinopyranose/fucose 633:662 arg1 transporter 681:691 the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter 623:691 the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) 623:698 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 8 23 theme million 1970:1976 arg1 cases 1978:1982 ~12 million cases currently 1966:1992 ~12 million cases currently 1966:1992 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 1 24 theme trypanosomatid 220:233 arg1 parasite 245:252 trypanosomatid protozoan parasite 220:252 The trypanosomatid protozoan parasite Leishmania 216:263 The trypanosomatid protozoan parasite Leishmania has a significant impact on human health globally. 36394313 10 25 theme several 2576:2582 arg1 candidates 2584:2593 several candidates 2576:2593 several candidates 2576:2593 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 0 26 theme GDP-Mannose/Fucose/Arabinopyranose 114:147 arg1 LPG2 161:164 the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 104:164 the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 104:164 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 6 27 gly fucosylated 1509:1519 arg1 glycans 1521:1527 fucosylated glycans 1509:1527 fucosylated glycans 1509:1527 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 10 28 theme potential 2404:2412 arg1 proteins 2414:2421 potential proteins 2404:2421 potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2 2404:2544 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 4 29 theme higher-energy 838:850 arg1 HCD 878:880 HCD 878:880 HCD 878:880 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 4 29 theme higher-energy 838:850 arg1 dissociation 864:875 higher-energy collisional dissociation 838:875 higher-energy collisional dissociation (HCD) 838:881 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 10 30 theme many 2555:2558 arg1 alterations 2560:2570 many alterations 2555:2570 many alterations 2555:2570 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 0 31 theme LPG2 161:164 arg1 Mutants 93:99 Null Mutants 88:99 Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1 88:213 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 5 32 theme proteomic 1053:1061 arg1 analysis 1063:1070 This deep proteomic analysis 1043:1070 This deep proteomic analysis 1043:1070 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 5 33 attach linked 1180:1185 arg2 changes 1172:1178 FUT1-dependent changes 1157:1178 FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins 1157:1248 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 5 33 attach linked 1180:1185 arg1 alterations 1197:1207 marked alterations 1190:1207 marked alterations within mitochondrion-associated proteins 1190:1248 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 8 34 dep IMPORTANCE 1878:1887 arg1 Leishmania 1889:1898 IMPORTANCE Leishmania 1878:1898 IMPORTANCE Leishmania 1878:1898 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 4 35 theme complementary 794:806 arg1 approaches 822:831 complementary fragmentation approaches 794:831 complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) 794:922 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 6 36 theme liquid 1600:1605 arg1 HILIC 1623:1627 HILIC 1623:1627 HILIC 1623:1627 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 6 36 theme liquid 1600:1605 arg1 chromatography 1607:1620 hydrophilic interaction liquid chromatography 1576:1620 hydrophilic interaction liquid chromatography (HILIC) enrichment 1576:1639 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 3 37 theme mitochondrial 708:720 arg1 FUT1 742:745 FUT1 742:745 FUT1 742:745 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 3 37 theme mitochondrial 708:720 arg1 fucosyltransferase 722:739 the mitochondrial fucosyltransferase 704:739 the mitochondrial fucosyltransferase (FUT1) 704:746 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 8 38 with humans 1953:1958 arg1 hundreds 2027:2034 hundreds 2027:2034 hundreds of millions asymptomatically infected 2027:2072 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 38 with humans 1953:1958 arg1 cases 1978:1982 ~12 million cases currently 1966:1992 ~12 million cases currently 1966:1992 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 11 39 theme mitochondrial 2719:2731 arg1 dysfunction 2733:2743 its strong mitochondrial dysfunction 2708:2743 its strong mitochondrial dysfunction 2708:2743 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 6 40 theme hydrophilic 1576:1586 arg1 HILIC 1623:1627 HILIC 1623:1627 HILIC 1623:1627 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 6 40 theme hydrophilic 1576:1586 arg1 chromatography 1607:1620 hydrophilic interaction liquid chromatography 1576:1620 hydrophilic interaction liquid chromatography (HILIC) enrichment 1576:1639 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 10 41 theme Golgi 2512:2516 arg1 LPG2 2541:2544 the Golgi nucleotide transporter LPG2 2508:2544 the Golgi nucleotide transporter LPG2 2508:2544 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 12 42 theme target 2870:2875 arg1 s 2877:2877 this vital protein's elusive target(s) 2841:2878 this vital protein's elusive target(s) 2841:2878 This suggests that this vital protein's elusive target(s) may be more complex than the methods used could detect or that this target may not be a protein but perhaps another glycoconjugate or glycolipid. 36394313 4 43 theme transfer 896:903 arg1 ETD 919:921 ETD 919:921 ETD 919:921 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 4 43 theme transfer 896:903 arg1 dissociation 905:916 electron transfer dissociation 887:916 electron transfer dissociation (ETD) 887:922 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 5 44 theme many 1289:1292 arg1 pathway 1328:1334 the secretory pathway 1314:1334 the secretory pathway 1314:1334 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 5 44 theme many 1289:1292 arg1 pathways 1294:1301 many pathways 1289:1301 many pathways 1289:1301 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 5 45 theme Δlpg2- 1126:1131 arg1 mutants 1144:1150 both Δlpg2- and Δfut1s mutants 1121:1150 mutants 1144:1150 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 10 46 theme " 2468:2468 arg1 phenotype 2470:2478 the "persistence-without-pathology" phenotype 2434:2478 the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2 2434:2544 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 11 47 theme peptides 2799:2806 arg1 fucosylation 2776:2787 fucosylation 2776:2787 fucosylation of either peptides or N-glycans 2776:2819 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 2 48 theme chemotherapy 452:463 arg1 targets 465:471 novel vaccination and chemotherapy targets 430:471 novel vaccination and chemotherapy targets 430:471 Understanding the pathways associated with virulence within this significant pathogen is critical for identifying novel vaccination and chemotherapy targets. 36394313 6 49 theme Leishmania 1536:1545 arg1 glycopeptides 1547:1559 Leishmania glycopeptides 1536:1559 Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment 1536:1639 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 5 50 theme Δfut1s 1137:1142 arg1 mutants 1144:1150 both Δlpg2- and Δfut1s mutants 1121:1150 mutants 1144:1150 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 11 51 theme fucosylation 2776:2787 arg1 examples 2764:2771 examples 2764:2771 examples of fucosylation of either peptides or N-glycans 2764:2819 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 11 52 theme FUT1 2675:2678 arg1 deletion 2626:2633 deletion 2626:2633 deletion of the mitochondrial fucosyltransferase FUT1 2626:2678 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 2 53 theme vaccination 436:446 arg1 targets 465:471 novel vaccination and chemotherapy targets 430:471 novel vaccination and chemotherapy targets 430:471 Understanding the pathways associated with virulence within this significant pathogen is critical for identifying novel vaccination and chemotherapy targets. 36394313 0 54 theme Expanded 0:7 arg1 Survey 19:24 Expanded Proteomic Survey 0:24 Expanded Proteomic Survey of the Human Parasite Leishmania major 0:63 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 5 55 theme quantitative 1093:1104 arg1 differences 1106:1116 significant quantitative differences 1081:1116 significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins 1081:1248 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 11 56 theme mitochondrial 2642:2654 arg1 FUT1 2675:2678 the mitochondrial fucosyltransferase FUT1 2638:2678 the mitochondrial fucosyltransferase FUT1 2638:2678 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 9 57 theme great 2199:2203 arg1 resource 2205:2212 a great resource 2197:2212 a great resource 2197:2212 This work advances knowledge of the experimental proteome by nearly 2-fold, to more than 6,500 proteins and thus provides a great resource to investigators seeking to decode how this parasite is transmitted and causes disease and to identify new targets for therapeutic intervention. 36394313 0 58 dep major 59:63 arg1 Leishmania 48:57 Leishmania 48:57 Leishmania 48:57 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 7 59 theme therapeutics 1864:1875 arg1 development 1842:1852 the development 1838:1852 the development of future therapeutics 1838:1875 This work provides a critical resource for the community on the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics. 36394313 3 60 theme ultradeep 507:515 arg1 approach 527:534 an ultradeep proteomic approach 504:534 an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1) 504:746 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 4 61 dep known 1010:1014 arg1 Leishmania 1016:1025 Leishmania 1016:1025 Leishmania 1016:1025 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 12 62 dep glycoconjugate 2996:3009 arg1 another 2988:2994 another 2988:2994 another 2988:2994 This suggests that this vital protein's elusive target(s) may be more complex than the methods used could detect or that this target may not be a protein but perhaps another glycoconjugate or glycolipid. 36394313 0 63 theme major 59:63 arg1 Parasite 39:46 the Human Parasite 29:46 the Human Parasite Leishmania major 29:63 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 0 64 theme Parasite 39:46 arg1 Survey 19:24 Expanded Proteomic Survey 0:24 Expanded Proteomic Survey of the Human Parasite Leishmania major 0:63 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 6 65 gly glycopeptides 1547:1559 arg2 glycopeptides 1547:1559 Leishmania glycopeptides 1536:1559 Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment 1536:1639 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 7 66 theme observable 1706:1715 arg1 proteome 1728:1735 the observable Leishmania proteome 1702:1735 the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics 1702:1875 This work provides a critical resource for the community on the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics. 36394313 8 67 dep mild 2008:2011 arg1 to 2013:2014 to 2013:2014 to 2013:2014 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 67 dep mild 2008:2011 arg1 fatal 2016:2020 fatal 2016:2020 fatal 2016:2020 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 9 68 theme new 2317:2319 arg1 targets 2321:2327 new targets 2317:2327 new targets for therapeutic intervention 2317:2356 This work advances knowledge of the experimental proteome by nearly 2-fold, to more than 6,500 proteins and thus provides a great resource to investigators seeking to decode how this parasite is transmitted and causes disease and to identify new targets for therapeutic intervention. 36394313 3 69 theme genes 593:597 arg1 understanding 551:563 our understanding 547:563 our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1) 547:746 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 5 70 with mutants 1144:1150 arg1 changes 1172:1178 FUT1-dependent changes 1157:1178 FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins 1157:1248 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 10 71 with mutants 2483:2489 arg1 deletion 2496:2503 deletion 2496:2503 deletion of the Golgi nucleotide transporter LPG2 2496:2544 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 0 72 theme Fucosyltransferase 191:208 arg1 FUT1 210:213 the Mitochondrial Fucosyltransferase FUT1 173:213 the Mitochondrial Fucosyltransferase FUT1 173:213 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 10 73 theme transporter 2529:2539 arg1 LPG2 2541:2544 the Golgi nucleotide transporter LPG2 2508:2544 the Golgi nucleotide transporter LPG2 2508:2544 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 9 74 theme experimental 2111:2122 arg1 proteome 2124:2131 the experimental proteome 2107:2131 the experimental proteome 2107:2131 This work advances knowledge of the experimental proteome by nearly 2-fold, to more than 6,500 proteins and thus provides a great resource to investigators seeking to decode how this parasite is transmitted and causes disease and to identify new targets for therapeutic intervention. 36394313 8 75 theme widespread 1905:1914 arg1 IMPORTANCE 1878:1887 IMPORTANCE Leishmania 1878:1898 IMPORTANCE Leishmania 1878:1898 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 75 theme widespread 1905:1914 arg1 humans 1953:1958 humans 1953:1958 humans 1953:1958 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 75 theme widespread 1905:1914 arg1 parasite 1941:1948 a widespread trypanosomatid protozoan parasite 1903:1948 a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected 1903:2072 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 1 76 theme human 293:297 arg1 health 299:304 human health 293:304 human health 293:304 The trypanosomatid protozoan parasite Leishmania has a significant impact on human health globally. 36394313 4 77 theme known 1010:1014 arg1 proteome 1033:1040 the experimentally known Leishmania major proteome 991:1040 the experimentally known Leishmania major proteome 991:1040 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 8 78 theme protozoan 1931:1939 arg1 IMPORTANCE 1878:1887 IMPORTANCE Leishmania 1878:1898 IMPORTANCE Leishmania 1878:1898 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 78 theme protozoan 1931:1939 arg1 humans 1953:1958 humans 1953:1958 humans 1953:1958 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 78 theme protozoan 1931:1939 arg1 parasite 1941:1948 a widespread trypanosomatid protozoan parasite 1903:1948 a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected 1903:2072 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 4 79 theme proteins 965:972 arg1 identification 936:949 the identification 932:949 the identification of over 6,500 proteins 932:972 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 4 80 theme deep 755:758 arg1 fractionation 768:780 deep peptide fractionation 755:780 deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) 755:922 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 3 81 theme nucleotide-sugar 664:679 arg1 LPG2 694:697 LPG2 694:697 LPG2 694:697 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 3 81 theme nucleotide-sugar 664:679 arg1 transporter 681:691 the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter 623:691 the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) 623:698 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 6 82 theme FUT1 1347:1350 arg1 enzyme 1352:1357 the FUT1 enzyme 1343:1357 the FUT1 enzyme 1343:1357 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 10 83 theme proteomics 2373:2382 arg1 approach 2384:2391 The ultradeep proteomics approach 2359:2391 The ultradeep proteomics approach 2359:2391 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 0 84 theme Golgi 108:112 arg1 LPG2 161:164 the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 104:164 the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 104:164 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 3 85 theme Golgi 627:631 arg1 LPG2 694:697 LPG2 694:697 LPG2 694:697 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 3 85 theme Golgi 627:631 arg1 transporter 681:691 the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter 623:691 the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) 623:698 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 0 86 from Changes 77:83 arg1 Mutants 93:99 Null Mutants 88:99 Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1 88:213 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 1 87 from impact 283:288 arg1 health 299:304 human health 293:304 human health 293:304 The trypanosomatid protozoan parasite Leishmania has a significant impact on human health globally. 36394313 5 88 theme LPG2-dependent 1257:1270 arg1 changes 1272:1278 LPG2-dependent changes 1257:1278 LPG2-dependent changes 1257:1278 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 1 89 theme protozoan 235:243 arg1 parasite 245:252 trypanosomatid protozoan parasite 220:252 The trypanosomatid protozoan parasite Leishmania 216:263 The trypanosomatid protozoan parasite Leishmania has a significant impact on human health globally. 36394313 7 90 from community 1689:1697 arg1 proteome 1728:1735 the observable Leishmania proteome 1702:1735 the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics 1702:1875 This work provides a critical resource for the community on the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics. 36394313 11 91 with mutant 2614:2619 arg1 deletion 2626:2633 deletion 2626:2633 deletion of the mitochondrial fucosyltransferase FUT1 2626:2678 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 6 92 theme fucosylated 1509:1519 arg1 glycans 1521:1527 fucosylated glycans 1509:1527 fucosylated glycans 1509:1527 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 1 93 contain has 265:267 arg2 impact 283:288 a significant impact 269:288 a significant impact on human health 269:304 The trypanosomatid protozoan parasite Leishmania has a significant impact on human health globally. 36394313 1 93 contain has 265:267 arg1 parasite 245:252 trypanosomatid protozoan parasite 220:252 The trypanosomatid protozoan parasite Leishmania 216:263 The trypanosomatid protozoan parasite Leishmania has a significant impact on human health globally. 36394313 5 94 theme deep 1048:1051 arg1 analysis 1063:1070 This deep proteomic analysis 1043:1070 This deep proteomic analysis 1043:1070 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 4 95 theme major 1027:1031 arg1 proteome 1033:1040 the experimentally known Leishmania major proteome 991:1040 the experimentally known Leishmania major proteome 991:1040 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 5 96 theme mitochondrion-associated 1216:1239 arg1 proteins 1241:1248 mitochondrion-associated proteins 1216:1248 mitochondrion-associated proteins 1216:1248 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 10 97 theme persistence-without-pathology 2439:2467 arg1 phenotype 2470:2478 the "persistence-without-pathology" phenotype 2434:2478 the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2 2434:2544 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 4 98 theme collisional 852:862 arg1 HCD 878:880 HCD 878:880 HCD 878:880 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 4 98 theme collisional 852:862 arg1 dissociation 864:875 higher-energy collisional dissociation 838:875 higher-energy collisional dissociation (HCD) 838:881 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 6 99 theme chromatography 1607:1620 arg1 enrichment 1630:1639 hydrophilic interaction liquid chromatography (HILIC) enrichment 1576:1639 hydrophilic interaction liquid chromatography (HILIC) enrichment 1576:1639 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 11 100 theme strong 2712:2717 arg1 dysfunction 2733:2743 its strong mitochondrial dysfunction 2708:2743 its strong mitochondrial dysfunction 2708:2743 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 3 101 from Leishmania 602:611 arg1 understanding 551:563 our understanding 547:563 our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1) 547:746 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 6 102 theme interaction 1588:1598 arg1 HILIC 1623:1627 HILIC 1623:1627 HILIC 1623:1627 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 6 102 theme interaction 1588:1598 arg1 chromatography 1607:1620 hydrophilic interaction liquid chromatography 1576:1620 hydrophilic interaction liquid chromatography (HILIC) enrichment 1576:1639 While the FUT1 enzyme has been shown to fucosylate peptides in vitro, no evidence for protein fucosylation was identified within our ultradeep analysis, nor did we observe fucosylated glycans within Leishmania glycopeptides isolated using hydrophilic interaction liquid chromatography (HILIC) enrichment. 36394313 5 103 theme secretory 1318:1326 arg1 pathway 1328:1334 the secretory pathway 1314:1334 the secretory pathway 1314:1334 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 10 104 theme mutants 2483:2489 arg1 phenotype 2470:2478 the "persistence-without-pathology" phenotype 2434:2478 the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2 2434:2544 The ultradeep proteomics approach identified potential proteins underlying the "persistence-without-pathology" phenotype of mutants with deletion of the Golgi nucleotide transporter LPG2, showing many alterations and several candidates. 36394313 4 105 theme fragmentation 808:820 arg1 approaches 822:831 complementary fragmentation approaches 794:831 complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) 794:922 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 11 106 theme N-glycans 2811:2819 arg1 fucosylation 2776:2787 fucosylation 2776:2787 fucosylation of either peptides or N-glycans 2776:2819 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 0 107 theme Null 88:91 arg1 Mutants 93:99 Null Mutants 88:99 Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1 88:213 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 7 108 theme changes 1772:1778 arg1 ablation 1810:1817 ablation 1810:1817 ablation 1810:1817 This work provides a critical resource for the community on the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics. 36394313 11 109 theme mutant 2614:2619 arg1 Studies 2596:2602 Studies 2596:2602 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 2596:2678 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 4 110 theme electron 887:894 arg1 ETD 919:921 ETD 919:921 ETD 919:921 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 4 110 theme electron 887:894 arg1 dissociation 905:916 electron transfer dissociation 887:916 electron transfer dissociation (ETD) 887:922 Using deep peptide fractionation followed by complementary fragmentation approaches with higher-energy collisional dissociation (HCD) and electron transfer dissociation (ETD) allowed the identification of over 6,500 proteins, nearly doubling the experimentally known Leishmania major proteome. 36394313 11 111 theme fucosyltransferase 2656:2673 arg1 FUT1 2675:2678 the mitochondrial fucosyltransferase FUT1 2638:2678 the mitochondrial fucosyltransferase FUT1 2638:2678 Studies of a rare mutant with deletion of the mitochondrial fucosyltransferase FUT1 revealed changes underlying its strong mitochondrial dysfunction but did not reveal examples of fucosylation of either peptides or N-glycans. 36394313 0 112 theme Proteomic 9:17 arg1 Survey 19:24 Expanded Proteomic Survey 0:24 Expanded Proteomic Survey of the Human Parasite Leishmania major 0:63 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 8 113 theme millions 2039:2046 arg1 hundreds 2027:2034 hundreds 2027:2034 hundreds of millions asymptomatically infected 2027:2072 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 8 113 theme millions 2039:2046 arg1 cases 1978:1982 ~12 million cases currently 1966:1992 ~12 million cases currently 1966:1992 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 5 114 theme significant 1081:1091 arg1 differences 1106:1116 significant quantitative differences 1081:1116 significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins 1081:1248 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 0 115 theme Transporter 149:159 arg1 LPG2 161:164 the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 104:164 the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 104:164 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 12 116 theme elusive 2862:2868 arg1 s 2877:2877 this vital protein's elusive target(s) 2841:2878 this vital protein's elusive target(s) 2841:2878 This suggests that this vital protein's elusive target(s) may be more complex than the methods used could detect or that this target may not be a protein but perhaps another glycoconjugate or glycolipid. 36394313 2 117 theme novel 430:434 arg1 targets 465:471 novel vaccination and chemotherapy targets 430:471 novel vaccination and chemotherapy targets 430:471 Understanding the pathways associated with virulence within this significant pathogen is critical for identifying novel vaccination and chemotherapy targets. 36394313 8 118 theme infected 2065:2072 arg1 millions 2039:2046 millions 2039:2046 millions asymptomatically infected 2039:2072 IMPORTANCE Leishmania is a widespread trypanosomatid protozoan parasite of humans, with ~12 million cases currently, ranging from mild to fatal, and hundreds of millions asymptomatically infected. 36394313 0 119 theme Human 33:37 arg1 Parasite 39:46 the Human Parasite 29:46 the Human Parasite Leishmania major 29:63 Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1. 36394313 7 120 theme phenotypic 1761:1770 arg1 changes 1772:1778 phenotypic changes 1761:1778 phenotypic changes 1761:1778 This work provides a critical resource for the community on the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics. 36394313 3 121 theme proteomic 517:525 arg1 approach 527:534 an ultradeep proteomic approach 504:534 an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1) 504:746 Within this study we leverage an ultradeep proteomic approach to improve our understanding of two virulence-associated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1). 36394313 5 122 theme marked 1190:1195 arg1 alterations 1197:1207 marked alterations 1190:1207 marked alterations within mitochondrion-associated proteins 1190:1248 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 2 123 theme significant 381:391 arg1 pathogen 393:400 this significant pathogen 376:400 this significant pathogen 376:400 Understanding the pathways associated with virulence within this significant pathogen is critical for identifying novel vaccination and chemotherapy targets. 36394313 5 124 from differences 1106:1116 arg1 mutants 1144:1150 both Δlpg2- and Δfut1s mutants 1121:1150 mutants 1144:1150 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 1 125 dep parasite 245:252 arg1 Leishmania 254:263 Leishmania 254:263 The trypanosomatid protozoan parasite Leishmania 216:263 The trypanosomatid protozoan parasite Leishmania has a significant impact on human health globally. 36394313 7 126 theme Leishmania 1717:1726 arg1 proteome 1728:1735 the observable Leishmania proteome 1702:1735 the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics 1702:1875 This work provides a critical resource for the community on the observable Leishmania proteome as well as highlighting phenotypic changes associated with LPG2 or FUT1, ablation of which may guide the development of future therapeutics. 36394313 5 127 theme FUT1-dependent 1157:1170 arg1 changes 1172:1178 FUT1-dependent changes 1157:1178 FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins 1157:1248 This deep proteomic analysis revealed significant quantitative differences in both Δlpg2- and Δfut1s mutants with FUT1-dependent changes linked to marked alterations within mitochondrion-associated proteins, while LPG2-dependent changes impacted many pathways, including the secretory pathway. 36394313 1 128 theme significant 271:281 arg1 impact 283:288 a significant impact 269:288 a significant impact on human health 269:304 The trypanosomatid protozoan parasite Leishmania has a significant impact on human health globally. 36000846 1 0 theme Ross 269:272 arg1 RRV 281:283 RRV 281:283 RRV 281:283 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 0 theme Ross 269:272 arg1 River 274:278 Ross River 269:278 Ross River (RRV) 269:284 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 13 1 theme intradermal 1994:2004 arg1 route 2016:2020 intradermal infection route 1994:2020 intradermal infection route 1994:2020 As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses. 36000846 3 2 dep arthritis 478:486 arg1 the 474:476 the 474:476 the 474:476 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 7 3 theme antiviral 1008:1016 arg1 responses 1018:1026 robust early antiviral responses 995:1026 robust early antiviral responses 995:1026 RRV grown in mammalian cells elicited robust early antiviral responses in the skin, while RRV grown in mosquito cells stimulated poorer early antiviral responses. 36000846 3 4 from infection 431:439 arg1 model 452:456 a mouse model 444:456 a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD) 444:551 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 0 5 theme N-Linked 0:7 arg1 Glycans 9:15 N-Linked Glycans 0:15 N-Linked Glycans 0:15 N-Linked Glycans Shape Skin Immune Responses during Arthritis and Myositis after Intradermal Infection with Ross River Virus. 36000846 1 6 theme several 197:203 arg1 virus 327:331 o'nyong-nyong (ONNV) virus 306:331 o'nyong-nyong (ONNV) virus 306:331 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 6 theme several 197:203 arg1 chikungunya 248:258 the chikungunya 244:258 the chikungunya (CHIKV) 244:266 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 6 theme several 197:203 arg1 Mayaro 287:292 Mayaro 287:292 Mayaro (MAYV) 287:299 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 6 theme several 197:203 arg1 River 274:278 Ross River 269:278 Ross River (RRV) 269:284 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 6 theme several 197:203 arg1 pathogens 223:231 several re-emerging human pathogens 197:231 several re-emerging human pathogens 197:231 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 10 7 theme IMPORTANCE 1569:1578 arg1 alphaviruses 1594:1605 IMPORTANCE Arthritogenic alphaviruses 1569:1605 IMPORTANCE Arthritogenic alphaviruses 1569:1605 IMPORTANCE Arthritogenic alphaviruses are transmitted via mosquito bites through the skin, potentially causing debilitating diseases. 36000846 7 8 theme robust 995:1000 arg1 responses 1018:1026 robust early antiviral responses 995:1026 robust early antiviral responses 995:1026 RRV grown in mammalian cells elicited robust early antiviral responses in the skin, while RRV grown in mosquito cells stimulated poorer early antiviral responses. 36000846 3 9 theme Ross 521:524 arg1 virus 532:536 Ross River virus 521:536 Ross River virus disease (RRVD) 521:551 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 1 10 theme human 217:221 arg1 virus 327:331 o'nyong-nyong (ONNV) virus 306:331 o'nyong-nyong (ONNV) virus 306:331 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 10 theme human 217:221 arg1 chikungunya 248:258 the chikungunya 244:258 the chikungunya (CHIKV) 244:266 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 10 theme human 217:221 arg1 Mayaro 287:292 Mayaro 287:292 Mayaro (MAYV) 287:299 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 10 theme human 217:221 arg1 River 274:278 Ross River 269:278 Ross River (RRV) 269:284 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 10 theme human 217:221 arg1 pathogens 223:231 several re-emerging human pathogens 197:231 several re-emerging human pathogens 197:231 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 8 11 theme glycan 1173:1178 arg1 profile 1180:1186 the glycan profile 1169:1186 the glycan profile of mosquito and mammalian cell-derived RRV 1169:1229 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 6 12 theme envelope 857:864 arg1 determinant 898:908 a key determinant 892:908 a key determinant of skin immune responses and disease severity 892:954 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 6 12 theme envelope 857:864 arg1 glycosylation 875:887 viral envelope N-linked glycosylation 851:887 viral envelope N-linked glycosylation 851:887 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 8 13 theme intradermal 1364:1374 arg1 infection 1376:1384 intradermal infection 1364:1384 intradermal infection 1364:1384 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 8 14 theme glycan 1128:1133 arg1 spectrometry 1140:1151 glycan mass spectrometry 1128:1151 glycan mass spectrometry 1128:1151 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 8 15 used used 1123:1126 arg2 We 1120:1121 We 1120:1121 We 1120:1121 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 3 16 theme virus 532:536 arg1 disease 538:544 Ross River virus disease 521:544 Ross River virus disease (RRVD) 521:551 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 3 16 theme virus 532:536 arg1 RRVD 547:550 RRVD 547:550 RRVD 547:550 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 8 17 theme cell-derived 1214:1225 arg1 RRV 1227:1229 mammalian cell-derived RRV 1204:1229 mammalian cell-derived RRV 1204:1229 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 13 18 theme immune 2134:2139 arg1 responses 2141:2149 skin immune responses 2129:2149 skin immune responses 2129:2149 As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses. 36000846 6 19 theme responses 925:933 arg1 determinant 898:908 a key determinant 892:908 a key determinant of skin immune responses and disease severity 892:954 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 6 19 theme responses 925:933 arg1 glycosylation 875:887 viral envelope N-linked glycosylation 851:887 viral envelope N-linked glycosylation 851:887 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 1 20 theme mosquito-borne 157:170 arg1 alphaviruses 140:151 Arthritogenic alphaviruses 126:151 Arthritogenic alphaviruses 126:151 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 20 theme mosquito-borne 157:170 arg1 arboviruses 172:182 mosquito-borne arboviruses 157:182 mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus 157:331 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 6 21 theme skin 913:916 arg1 responses 925:933 skin immune responses 913:933 skin immune responses 913:933 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 4 22 theme inflammatory 621:632 arg1 monocytes 634:642 inflammatory monocytes 621:642 inflammatory monocytes 621:642 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 13 23 theme future 2104:2109 arg1 investigations 2111:2124 future investigations 2104:2124 future investigations of skin immune responses 2104:2149 As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses. 36000846 12 24 theme viral 1946:1950 arg1 glycosylation 1970:1982 viral envelope N-linked glycosylation 1946:1982 viral envelope N-linked glycosylation 1946:1982 Intradermal arbovirus infection described herein results in musculoskeletal pathology, which is dependent on viral envelope N-linked glycosylation. 36000846 4 25 theme neutrophils 648:658 arg1 recruitment 606:616 the recruitment 602:616 the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin 602:744 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 4 26 theme draining 708:715 arg1 LN 730:731 LN 730:731 LN 730:731 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 4 26 theme draining 708:715 arg1 nodes 723:727 draining lymph nodes 708:727 draining lymph nodes (LN) of the skin 708:744 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 7 27 theme early 1093:1097 arg1 responses 1109:1117 poorer early antiviral responses 1086:1117 poorer early antiviral responses 1086:1117 RRV grown in mammalian cells elicited robust early antiviral responses in the skin, while RRV grown in mosquito cells stimulated poorer early antiviral responses. 36000846 9 28 theme envelope 1509:1516 arg1 glycoprotein 1518:1529 envelope glycoprotein 1509:1529 envelope glycoprotein glycosylation 1509:1543 Altogether, our findings demonstrate skin infection with an arthritogenic alphavirus leads to musculoskeletal disease and envelope glycoprotein glycosylation shapes disease outcome. 36000846 3 29 with humans 509:514 arg1 disease 538:544 Ross River virus disease 521:544 Ross River virus disease (RRVD) 521:551 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 3 29 with humans 509:514 arg1 RRVD 547:550 RRVD 547:550 RRVD 547:550 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 4 30 theme dendritic 681:689 arg1 cells 691:695 dendritic cells 681:695 dendritic cells 681:695 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 3 31 theme intradermal 415:425 arg1 infection 431:439 intradermal RRV infection 415:439 intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD) 415:551 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 7 32 theme mosquito 1060:1067 arg1 cells 1069:1073 mosquito cells 1060:1073 mosquito cells 1060:1073 RRV grown in mammalian cells elicited robust early antiviral responses in the skin, while RRV grown in mosquito cells stimulated poorer early antiviral responses. 36000846 9 33 theme disease 1552:1558 arg1 outcome 1560:1566 disease outcome 1552:1566 disease outcome 1552:1566 Altogether, our findings demonstrate skin infection with an arthritogenic alphavirus leads to musculoskeletal disease and envelope glycoprotein glycosylation shapes disease outcome. 36000846 8 34 theme skin 1312:1315 arg1 responses 1324:1332 curtailed skin immune responses 1302:1332 curtailed skin immune responses 1302:1332 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 0 35 theme Immune 28:33 arg1 Responses 35:43 Skin Immune Responses 23:43 Skin Immune Responses 23:43 N-Linked Glycans Shape Skin Immune Responses during Arthritis and Myositis after Intradermal Infection with Ross River Virus. 36000846 8 36 gly glycoprotein 1270:1281 arg1 glycoprotein 1270:1281 the RRV E2 glycoprotein 1259:1281 the RRV E2 glycoprotein 1259:1281 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 6 37 theme disease 939:945 arg1 severity 947:954 disease severity 939:954 disease severity 939:954 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 9 38 gly glycoprotein 1518:1529 arg1 glycoprotein 1518:1529 envelope glycoprotein 1509:1529 envelope glycoprotein glycosylation 1509:1543 Altogether, our findings demonstrate skin infection with an arthritogenic alphavirus leads to musculoskeletal disease and envelope glycoprotein glycosylation shapes disease outcome. 36000846 4 39 theme skin 741:744 arg1 LN 730:731 LN 730:731 LN 730:731 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 4 39 theme skin 741:744 arg1 nodes 723:727 draining lymph nodes 708:727 draining lymph nodes (LN) of the skin 708:744 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 12 40 theme Intradermal 1837:1847 arg1 infection 1859:1867 Intradermal arbovirus infection 1837:1867 Intradermal arbovirus infection described herein 1837:1884 Intradermal arbovirus infection described herein results in musculoskeletal pathology, which is dependent on viral envelope N-linked glycosylation. 36000846 11 41 theme viral 1728:1732 arg1 infection 1734:1742 viral infection 1728:1742 viral infection 1728:1742 Our understanding of how viral infection starts in the skin and how virus systemically disseminates to cause disease remains limited. 36000846 8 42 theme reduced 1338:1344 arg1 disease 1346:1352 reduced disease 1338:1352 reduced disease following intradermal infection 1338:1384 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 2 43 theme mosquito 368:375 arg1 bite 377:380 a mosquito bite 366:380 a mosquito bite to the skin 366:392 Arboviruses are transmitted via a mosquito bite to the skin. 36000846 8 44 link cell-derived 1214:1225 arg1 RRV 1227:1229 mammalian cell-derived RRV 1204:1229 mammalian cell-derived RRV 1204:1229 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 13 45 theme re-emerging 2182:2192 arg1 arboviruses 2194:2204 other re-emerging arboviruses 2176:2204 other re-emerging arboviruses 2176:2204 As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses. 36000846 7 46 theme early 1002:1006 arg1 responses 1018:1026 robust early antiviral responses 995:1026 robust early antiviral responses 995:1026 RRV grown in mammalian cells elicited robust early antiviral responses in the skin, while RRV grown in mosquito cells stimulated poorer early antiviral responses. 36000846 13 47 theme infection 2006:2014 arg1 route 2016:2020 intradermal infection route 1994:2020 intradermal infection route 1994:2020 As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses. 36000846 8 48 theme mass 1135:1138 arg1 spectrometry 1140:1151 glycan mass spectrometry 1128:1151 glycan mass spectrometry 1128:1151 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 10 49 theme Arthritogenic 1580:1592 arg1 alphaviruses 1594:1605 IMPORTANCE Arthritogenic alphaviruses 1569:1605 IMPORTANCE Arthritogenic alphaviruses 1569:1605 IMPORTANCE Arthritogenic alphaviruses are transmitted via mosquito bites through the skin, potentially causing debilitating diseases. 36000846 1 50 theme re-emerging 205:215 arg1 virus 327:331 o'nyong-nyong (ONNV) virus 306:331 o'nyong-nyong (ONNV) virus 306:331 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 50 theme re-emerging 205:215 arg1 chikungunya 248:258 the chikungunya 244:258 the chikungunya (CHIKV) 244:266 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 50 theme re-emerging 205:215 arg1 Mayaro 287:292 Mayaro 287:292 Mayaro (MAYV) 287:299 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 50 theme re-emerging 205:215 arg1 River 274:278 Ross River 269:278 Ross River (RRV) 269:284 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 50 theme re-emerging 205:215 arg1 pathogens 223:231 several re-emerging human pathogens 197:231 several re-emerging human pathogens 197:231 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 7 51 theme mammalian 970:978 arg1 cells 980:984 mammalian cells 970:984 mammalian cells 970:984 RRV grown in mammalian cells elicited robust early antiviral responses in the skin, while RRV grown in mosquito cells stimulated poorer early antiviral responses. 36000846 0 52 with Infection 93:101 arg1 Virus 119:123 Ross River Virus 108:123 Ross River Virus 108:123 N-Linked Glycans Shape Skin Immune Responses during Arthritis and Myositis after Intradermal Infection with Ross River Virus. 36000846 6 53 theme N-linked 866:873 arg1 determinant 898:908 a key determinant 892:908 a key determinant of skin immune responses and disease severity 892:954 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 6 53 theme N-linked 866:873 arg1 glycosylation 875:887 viral envelope N-linked glycosylation 851:887 viral envelope N-linked glycosylation 851:887 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 6 54 link N-linked 866:873 arg1 determinant 898:908 a key determinant 892:908 a key determinant of skin immune responses and disease severity 892:954 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 6 54 link N-linked 866:873 arg1 glycosylation 875:887 viral envelope N-linked glycosylation 851:887 viral envelope N-linked glycosylation 851:887 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 12 55 theme N-linked 1961:1968 arg1 glycosylation 1970:1982 viral envelope N-linked glycosylation 1946:1982 viral envelope N-linked glycosylation 1946:1982 Intradermal arbovirus infection described herein results in musculoskeletal pathology, which is dependent on viral envelope N-linked glycosylation. 36000846 6 56 theme viral 851:855 arg1 determinant 898:908 a key determinant 892:908 a key determinant of skin immune responses and disease severity 892:954 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 6 56 theme viral 851:855 arg1 glycosylation 875:887 viral envelope N-linked glycosylation 851:887 viral envelope N-linked glycosylation 851:887 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 4 57 theme skin 567:570 arg1 infection 572:580 skin infection 567:580 skin infection with RRV 567:589 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 13 58 theme other 2176:2180 arg1 arboviruses 2194:2204 other re-emerging arboviruses 2176:2204 other re-emerging arboviruses 2176:2204 As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses. 36000846 3 59 theme River 526:530 arg1 virus 532:536 Ross River virus 521:536 Ross River virus disease (RRVD) 521:551 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 9 60 theme skin 1424:1427 arg1 infection 1429:1437 skin infection 1424:1437 skin infection with an arthritogenic alphavirus 1424:1470 Altogether, our findings demonstrate skin infection with an arthritogenic alphavirus leads to musculoskeletal disease and envelope glycoprotein glycosylation shapes disease outcome. 36000846 8 61 theme mosquito 1191:1198 arg1 profile 1180:1186 the glycan profile 1169:1186 the glycan profile of mosquito and mammalian cell-derived RRV 1169:1229 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 13 62 theme skin 2129:2132 arg1 responses 2141:2149 skin immune responses 2129:2149 skin immune responses 2129:2149 As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses. 36000846 1 63 theme Arthritogenic 126:138 arg1 alphaviruses 140:151 Arthritogenic alphaviruses 126:151 Arthritogenic alphaviruses 126:151 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 1 63 theme Arthritogenic 126:138 arg1 arboviruses 172:182 mosquito-borne arboviruses 157:182 mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus 157:331 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 8 64 theme mammalian 1204:1212 arg1 RRV 1227:1229 mammalian cell-derived RRV 1204:1229 mammalian cell-derived RRV 1204:1229 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 13 65 theme responses 2141:2149 arg1 investigations 2111:2124 future investigations 2104:2124 future investigations of skin immune responses 2104:2149 As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses. 36000846 9 66 theme arthritogenic 1447:1459 arg1 alphavirus 1461:1470 an arthritogenic alphavirus 1444:1470 an arthritogenic alphavirus 1444:1470 Altogether, our findings demonstrate skin infection with an arthritogenic alphavirus leads to musculoskeletal disease and envelope glycoprotein glycosylation shapes disease outcome. 36000846 6 67 theme immune 918:923 arg1 responses 925:933 skin immune responses 913:933 skin immune responses 913:933 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 8 68 theme RRV 1227:1229 arg1 profile 1180:1186 the glycan profile 1169:1186 the glycan profile of mosquito and mammalian cell-derived RRV 1169:1229 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 0 69 theme Intradermal 81:91 arg1 Infection 93:101 Intradermal Infection 81:101 Intradermal Infection with Ross River Virus 81:123 N-Linked Glycans Shape Skin Immune Responses during Arthritis and Myositis after Intradermal Infection with Ross River Virus. 36000846 1 70 theme o'nyong-nyong 306:318 arg1 virus 327:331 o'nyong-nyong (ONNV) virus 306:331 o'nyong-nyong (ONNV) virus 306:331 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 12 71 link N-linked 1961:1968 arg1 glycosylation 1970:1982 viral envelope N-linked glycosylation 1946:1982 viral envelope N-linked glycosylation 1946:1982 Intradermal arbovirus infection described herein results in musculoskeletal pathology, which is dependent on viral envelope N-linked glycosylation. 36000846 7 72 theme antiviral 1099:1107 arg1 responses 1109:1117 poorer early antiviral responses 1086:1117 poorer early antiviral responses 1086:1117 RRV grown in mammalian cells elicited robust early antiviral responses in the skin, while RRV grown in mosquito cells stimulated poorer early antiviral responses. 36000846 1 73 theme ONNV 321:324 arg1 virus 327:331 o'nyong-nyong (ONNV) virus 306:331 o'nyong-nyong (ONNV) virus 306:331 Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. 36000846 12 74 theme envelope 1952:1959 arg1 glycosylation 1970:1982 viral envelope N-linked glycosylation 1946:1982 viral envelope N-linked glycosylation 1946:1982 Intradermal arbovirus infection described herein results in musculoskeletal pathology, which is dependent on viral envelope N-linked glycosylation. 36000846 9 75 theme musculoskeletal 1481:1495 arg1 disease 1497:1503 musculoskeletal disease 1481:1503 musculoskeletal disease 1481:1503 Altogether, our findings demonstrate skin infection with an arthritogenic alphavirus leads to musculoskeletal disease and envelope glycoprotein glycosylation shapes disease outcome. 36000846 6 76 theme key 894:896 arg1 determinant 898:908 a key determinant 892:908 a key determinant of skin immune responses and disease severity 892:954 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 6 76 theme key 894:896 arg1 glycosylation 875:887 viral envelope N-linked glycosylation 851:887 viral envelope N-linked glycosylation 851:887 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 0 77 theme River 113:117 arg1 Virus 119:123 Ross River Virus 108:123 Ross River Virus 108:123 N-Linked Glycans Shape Skin Immune Responses during Arthritis and Myositis after Intradermal Infection with Ross River Virus. 36000846 8 78 theme RRV 1263:1265 arg1 glycoprotein 1270:1281 the RRV E2 glycoprotein 1259:1281 the RRV E2 glycoprotein 1259:1281 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 7 79 theme poorer 1086:1091 arg1 responses 1109:1117 poorer early antiviral responses 1086:1117 poorer early antiviral responses 1086:1117 RRV grown in mammalian cells elicited robust early antiviral responses in the skin, while RRV grown in mosquito cells stimulated poorer early antiviral responses. 36000846 8 80 gly deglycosylation 1240:1254 arg1 glycoprotein 1270:1281 the RRV E2 glycoprotein 1259:1281 the RRV E2 glycoprotein 1259:1281 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 9 81 theme glycoprotein 1518:1529 arg1 glycosylation 1531:1543 envelope glycoprotein glycosylation 1509:1543 envelope glycoprotein glycosylation 1509:1543 Altogether, our findings demonstrate skin infection with an arthritogenic alphavirus leads to musculoskeletal disease and envelope glycoprotein glycosylation shapes disease outcome. 36000846 9 82 with infection 1429:1437 arg1 alphavirus 1461:1470 an arthritogenic alphavirus 1444:1470 an arthritogenic alphavirus 1444:1470 Altogether, our findings demonstrate skin infection with an arthritogenic alphavirus leads to musculoskeletal disease and envelope glycoprotein glycosylation shapes disease outcome. 36000846 8 83 theme glycoprotein 1270:1281 arg1 deglycosylation 1240:1254 deglycosylation 1240:1254 deglycosylation of the RRV E2 glycoprotein 1240:1281 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 10 84 theme mosquito 1627:1634 arg1 bites 1636:1640 mosquito bites 1627:1640 mosquito bites 1627:1640 IMPORTANCE Arthritogenic alphaviruses are transmitted via mosquito bites through the skin, potentially causing debilitating diseases. 36000846 0 85 theme Skin 23:26 arg1 Responses 35:43 Skin Immune Responses 23:43 Skin Immune Responses 23:43 N-Linked Glycans Shape Skin Immune Responses during Arthritis and Myositis after Intradermal Infection with Ross River Virus. 36000846 8 86 theme E2 1267:1268 arg1 glycoprotein 1270:1281 the RRV E2 glycoprotein 1259:1281 the RRV E2 glycoprotein 1259:1281 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 3 87 theme RRV 427:429 arg1 infection 431:439 intradermal RRV infection 415:439 intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD) 415:551 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 12 88 theme musculoskeletal 1897:1911 arg1 pathology 1913:1921 musculoskeletal pathology 1897:1921 musculoskeletal pathology 1897:1921 Intradermal arbovirus infection described herein results in musculoskeletal pathology, which is dependent on viral envelope N-linked glycosylation. 36000846 13 89 with infection 2161:2169 arg1 arboviruses 2194:2204 other re-emerging arboviruses 2176:2204 other re-emerging arboviruses 2176:2204 As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses. 36000846 6 90 theme severity 947:954 arg1 determinant 898:908 a key determinant 892:908 a key determinant of skin immune responses and disease severity 892:954 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 6 90 theme severity 947:954 arg1 glycosylation 875:887 viral envelope N-linked glycosylation 851:887 viral envelope N-linked glycosylation 851:887 We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. 36000846 8 91 theme curtailed 1302:1310 arg1 responses 1324:1332 curtailed skin immune responses 1302:1332 curtailed skin immune responses 1302:1332 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 0 92 theme Ross 108:111 arg1 Virus 119:123 Ross River Virus 108:123 Ross River Virus 108:123 N-Linked Glycans Shape Skin Immune Responses during Arthritis and Myositis after Intradermal Infection with Ross River Virus. 36000846 12 93 theme arbovirus 1849:1857 arg1 infection 1859:1867 Intradermal arbovirus infection 1837:1867 Intradermal arbovirus infection described herein 1837:1884 Intradermal arbovirus infection described herein results in musculoskeletal pathology, which is dependent on viral envelope N-linked glycosylation. 36000846 4 94 with infection 572:580 arg1 RRV 587:589 RRV 587:589 RRV 587:589 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 8 95 theme immune 1317:1322 arg1 responses 1324:1332 curtailed skin immune responses 1302:1332 curtailed skin immune responses 1302:1332 We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. 36000846 3 96 theme mouse 446:450 arg1 model 452:456 a mouse model 444:456 a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD) 444:551 Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). 36000846 4 97 theme lymph 717:721 arg1 LN 730:731 LN 730:731 LN 730:731 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 4 97 theme lymph 717:721 arg1 nodes 723:727 draining lymph nodes 708:727 draining lymph nodes (LN) of the skin 708:744 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 36000846 10 98 theme debilitating 1680:1691 arg1 diseases 1693:1700 debilitating diseases 1680:1700 debilitating diseases 1680:1700 IMPORTANCE Arthritogenic alphaviruses are transmitted via mosquito bites through the skin, potentially causing debilitating diseases. 36000846 13 99 theme new 2031:2033 arg1 insights 2035:2042 new insights 2031:2042 new insights into how arboviruses cause disease 2031:2077 As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses. 36000846 4 100 theme monocytes 634:642 arg1 recruitment 606:616 the recruitment 602:616 the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin 602:744 We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. 35626143 6 0 theme potential 965:973 arg1 s 985:985 the potential mechanism(s) 961:986 the potential mechanism(s) of action for the observed combinatorial effects 961:1035 To understand the potential mechanism(s) of action for the observed combinatorial effects, single-cell RNA sequencing was performed using mouse tumors treated with Mito-HNK, Mito-LND, and their combination. 35626143 7 1 theme tumor 1162:1166 arg1 cells 1168:1172 lung tumor cells 1157:1172 lung tumor cells 1157:1172 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 2 2 theme mitochondrial 366:378 arg1 complexes 380:388 mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling 366:423 mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling 366:423 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 2 theme mitochondrial 366:378 arg1 I/II 390:393 I/II 390:393 I/II 390:393 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 2 theme mitochondrial 366:378 arg1 signaling 415:423 AKT/mTOR/p70S6K signaling 399:423 AKT/mTOR/p70S6K signaling 399:423 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 4 3 theme liver 661:665 arg1 toxicity 667:674 liver toxicity 661:674 liver toxicity 661:674 No evidence of toxicity (including liver toxicity) was detected by monitoring serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. 35626143 3 4 theme post-carcinogen 566:580 arg1 treatment 582:590 one-week post-carcinogen treatment 557:590 one-week post-carcinogen treatment 557:590 All chemopreventive treatments began one-week post-carcinogen treatment and continued daily for 24 weeks. 35626143 4 5 theme alanine 720:726 arg1 aminotransferase 728:743 alanine aminotransferase 720:743 alanine aminotransferase 720:743 No evidence of toxicity (including liver toxicity) was detected by monitoring serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. 35626143 2 6 theme phosphorylation 284:298 arg1 honokiol 213:220 mitochondria-targeted honokiol 191:220 mitochondria-targeted honokiol (Mito-HNK) 191:231 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 6 theme phosphorylation 284:298 arg1 inhibitor 237:245 an inhibitor 234:245 an inhibitor of mitochondrial complex I and STAT3 phosphorylation 234:298 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 5 7 theme tumor 928:932 arg1 load 934:937 tumor load 928:937 tumor load 928:937 Mito-HNK or Mito-LND treatment alone reduced tumor load by 56% and 48%, respectively, whereas the combination of Mito-HNK and Mito-LND reduced tumor load by 83%. 35626143 11 8 with combination 1902:1912 arg1 Mito-LND 1931:1938 Mito-LND 1931:1938 Mito-LND 1931:1938 Therefore, the combination of Mito-HNK with Mito-LND may present an effective strategy for lung cancer chemoprevention. 35626143 11 9 theme Mito-HNK 1917:1924 arg1 combination 1902:1912 the combination 1898:1912 the combination of Mito-HNK with Mito-LND 1898:1938 Therefore, the combination of Mito-HNK with Mito-LND may present an effective strategy for lung cancer chemoprevention. 35626143 5 10 theme Mito-HNK 898:905 arg1 combination 883:893 the combination 879:893 the combination of Mito-HNK and Mito-LND 879:918 Mito-HNK or Mito-LND treatment alone reduced tumor load by 56% and 48%, respectively, whereas the combination of Mito-HNK and Mito-LND reduced tumor load by 83%. 35626143 6 11 theme action 991:996 arg1 s 985:985 the potential mechanism(s) 961:986 the potential mechanism(s) of action for the observed combinatorial effects 961:1035 To understand the potential mechanism(s) of action for the observed combinatorial effects, single-cell RNA sequencing was performed using mouse tumors treated with Mito-HNK, Mito-LND, and their combination. 35626143 7 12 theme genes 1220:1224 arg1 glycolysis 1290:1299 glycolysis 1290:1299 glycolysis 1290:1299 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 7 12 theme genes 1220:1224 arg1 signaling 1312:1320 STAT3 signaling 1306:1320 STAT3 signaling 1306:1320 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 7 12 theme genes 1220:1224 arg1 phosphorylation 1273:1287 oxidative phosphorylation 1263:1287 oxidative phosphorylation 1263:1287 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 7 12 theme genes 1220:1224 arg1 expression 1206:1215 the expression 1202:1215 the expression of genes involved in mitochondrial complex ǀ 1202:1260 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 9 13 theme Mito-HNK 1525:1532 arg1 combination 1510:1520 a combination 1508:1520 a combination of Mito-HNK with Mito-LND 1508:1546 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 11 14 theme lung 1978:1981 arg1 chemoprevention 1990:2004 lung cancer chemoprevention 1978:2004 lung cancer chemoprevention 1978:2004 Therefore, the combination of Mito-HNK with Mito-LND may present an effective strategy for lung cancer chemoprevention. 35626143 8 15 theme genes 1360:1364 arg1 expression 1346:1355 the expression 1342:1355 the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells 1342:1475 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 7 16 theme oxidative 1263:1271 arg1 phosphorylation 1273:1287 oxidative phosphorylation 1263:1287 oxidative phosphorylation 1263:1287 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 10 17 theme mTOR 1870:1873 arg1 signaling 1875:1883 mTOR signaling 1870:1883 mTOR signaling 1870:1883 Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). 35626143 1 18 theme cancer 161:166 arg1 chemoprevention 168:182 lung cancer chemoprevention 156:182 lung cancer chemoprevention 156:182 Combined treatment targeting mitochondria may improve the efficacy of lung cancer chemoprevention. 35626143 6 19 theme RNA 1050:1052 arg1 sequencing 1054:1063 single-cell RNA sequencing 1038:1063 single-cell RNA sequencing 1038:1063 To understand the potential mechanism(s) of action for the observed combinatorial effects, single-cell RNA sequencing was performed using mouse tumors treated with Mito-HNK, Mito-LND, and their combination. 35626143 8 20 theme mitochondrial 1370:1382 arg1 complexes 1384:1392 mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling 1370:1455 mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling 1370:1455 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 8 20 theme mitochondrial 1370:1382 arg1 signaling 1447:1455 AKT/mTOR/p70S6K signaling 1431:1455 AKT/mTOR/p70S6K signaling 1431:1455 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 8 20 theme mitochondrial 1370:1382 arg1 phosphorylation 1410:1424 oxidative phosphorylation 1400:1424 oxidative phosphorylation 1400:1424 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 8 20 theme mitochondrial 1370:1382 arg1 I/II 1394:1397 I/II 1394:1397 I/II 1394:1397 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 8 21 from expression 1346:1355 arg1 cells 1471:1475 lung tumor cells 1460:1475 lung tumor cells 1460:1475 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 2 22 dep complexes 380:388 arg1 complexes 380:388 mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling 366:423 mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling 366:423 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 22 dep complexes 380:388 arg1 I/II 390:393 I/II 390:393 I/II 390:393 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 22 dep complexes 380:388 arg1 signaling 415:423 AKT/mTOR/p70S6K signaling 399:423 AKT/mTOR/p70S6K signaling 399:423 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 7 23 theme mitochondrial 1238:1250 arg1 ǀ 1260:1260 mitochondrial complex ǀ 1238:1260 mitochondrial complex ǀ 1238:1260 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 6 24 theme combinatorial 1015:1027 arg1 effects 1029:1035 the observed combinatorial effects 1002:1035 the observed combinatorial effects 1002:1035 To understand the potential mechanism(s) of action for the observed combinatorial effects, single-cell RNA sequencing was performed using mouse tumors treated with Mito-HNK, Mito-LND, and their combination. 35626143 8 25 theme oxidative 1400:1408 arg1 complexes 1384:1392 mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling 1370:1455 mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling 1370:1455 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 8 25 theme oxidative 1400:1408 arg1 phosphorylation 1410:1424 oxidative phosphorylation 1400:1424 oxidative phosphorylation 1400:1424 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 1 26 theme Combined 86:93 arg1 treatment 95:103 Combined treatment 86:103 Combined treatment targeting mitochondria 86:126 Combined treatment targeting mitochondria may improve the efficacy of lung cancer chemoprevention. 35626143 2 27 theme mouse 493:497 arg1 carcinogenesis 504:517 mouse lung carcinogenesis 493:517 mouse lung carcinogenesis 493:517 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 8 28 theme AKT/mTOR/p70S6K 1431:1445 arg1 signaling 1447:1455 AKT/mTOR/p70S6K signaling 1431:1455 AKT/mTOR/p70S6K signaling 1431:1455 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 8 28 theme AKT/mTOR/p70S6K 1431:1445 arg1 complexes 1384:1392 mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling 1370:1455 mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling 1370:1455 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 2 29 theme combinational 451:463 arg1 efficacy 481:488 their combinational chemopreventive efficacy 445:488 their combinational chemopreventive efficacy on mouse lung carcinogenesis 445:517 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 0 30 theme Lung 19:22 arg1 Cancer 24:29 Lung Cancer 19:29 Lung Cancer 19:29 Chemoprevention of Lung Cancer with a Combination of Mitochondria-Targeted Compounds. 35626143 9 31 theme lung 1643:1646 arg1 cells 1654:1658 lung tumor cells 1643:1658 lung tumor cells 1643:1658 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 4 32 theme aminotransferase 759:774 arg1 levels 710:715 serum levels 704:715 serum levels of alanine aminotransferase and aspartate aminotransferase enzymes 704:782 No evidence of toxicity (including liver toxicity) was detected by monitoring serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. 35626143 2 33 theme mitochondria-targeted 191:211 arg1 Mito-HNK 223:230 Mito-HNK 223:230 Mito-HNK 223:230 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 33 theme mitochondria-targeted 191:211 arg1 honokiol 213:220 mitochondria-targeted honokiol 191:220 mitochondria-targeted honokiol (Mito-HNK) 191:231 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 33 theme mitochondria-targeted 191:211 arg1 inhibitor 237:245 an inhibitor 234:245 an inhibitor of mitochondrial complex I and STAT3 phosphorylation 234:298 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 10 34 theme Mito-HNK 1734:1741 arg1 efficacy 1722:1729 the antitumor efficacy 1708:1729 the antitumor efficacy of Mito-HNK 1708:1741 Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). 35626143 0 35 theme Mitochondria-Targeted 53:73 arg1 Compounds 75:83 Mitochondria-Targeted Compounds 53:83 Mitochondria-Targeted Compounds 53:83 Chemoprevention of Lung Cancer with a Combination of Mitochondria-Targeted Compounds. 35626143 8 36 theme tumor 1465:1469 arg1 cells 1471:1475 lung tumor cells 1460:1475 lung tumor cells 1460:1475 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 10 37 theme common 1775:1780 arg1 targets 1782:1788 common targets 1775:1788 common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling) 1775:1884 Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). 35626143 10 37 theme common 1775:1780 arg1 phosphorylation 1801:1815 oxidative phosphorylation 1791:1815 oxidative phosphorylation 1791:1815 Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). 35626143 2 38 theme complex 264:270 arg1 I 272:272 mitochondrial complex I 250:272 mitochondrial complex I 250:272 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 0 39 with Chemoprevention 0:14 arg1 Combination 38:48 a Combination 36:48 a Combination of Mitochondria-Targeted Compounds 36:83 Chemoprevention of Lung Cancer with a Combination of Mitochondria-Targeted Compounds. 35626143 3 40 theme chemopreventive 524:538 arg1 treatments 540:549 All chemopreventive treatments 520:549 All chemopreventive treatments 520:549 All chemopreventive treatments began one-week post-carcinogen treatment and continued daily for 24 weeks. 35626143 4 41 dep aminotransferase 728:743 arg1 enzymes 776:782 enzymes 776:782 enzymes 776:782 No evidence of toxicity (including liver toxicity) was detected by monitoring serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. 35626143 7 42 theme STAT3 1306:1310 arg1 signaling 1312:1320 STAT3 signaling 1306:1320 STAT3 signaling 1306:1320 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 6 43 theme mechanism 975:983 arg1 s 985:985 the potential mechanism(s) 961:986 the potential mechanism(s) of action for the observed combinatorial effects 961:1035 To understand the potential mechanism(s) of action for the observed combinatorial effects, single-cell RNA sequencing was performed using mouse tumors treated with Mito-HNK, Mito-LND, and their combination. 35626143 7 44 theme lung 1157:1160 arg1 cells 1168:1172 lung tumor cells 1157:1172 lung tumor cells 1157:1172 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 2 45 theme complexes 380:388 arg1 inhibitor 353:361 an inhibitor 350:361 an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling 350:423 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 45 theme complexes 380:388 arg1 lonidamine 327:336 mitochondria-targeted lonidamine 305:336 mitochondria-targeted lonidamine (Mito-LND) 305:347 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 9 46 from metabolism 1579:1588 arg1 cells 1654:1658 lung tumor cells 1643:1658 lung tumor cells 1643:1658 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 4 47 theme toxicity 641:648 arg1 evidence 629:636 No evidence 626:636 No evidence of toxicity (including liver toxicity) 626:675 No evidence of toxicity (including liver toxicity) was detected by monitoring serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. 35626143 2 48 theme mitochondria-targeted 305:325 arg1 inhibitor 353:361 an inhibitor 350:361 an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling 350:423 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 48 theme mitochondria-targeted 305:325 arg1 Mito-LND 339:346 Mito-LND 339:346 Mito-LND 339:346 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 48 theme mitochondria-targeted 305:325 arg1 lonidamine 327:336 mitochondria-targeted lonidamine 305:336 mitochondria-targeted lonidamine (Mito-LND) 305:347 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 6 49 theme observed 1006:1013 arg1 effects 1029:1035 the observed combinatorial effects 1002:1035 the observed combinatorial effects 1002:1035 To understand the potential mechanism(s) of action for the observed combinatorial effects, single-cell RNA sequencing was performed using mouse tumors treated with Mito-HNK, Mito-LND, and their combination. 35626143 4 50 theme aminotransferase 728:743 arg1 levels 710:715 serum levels 704:715 serum levels of alanine aminotransferase and aspartate aminotransferase enzymes 704:782 No evidence of toxicity (including liver toxicity) was detected by monitoring serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. 35626143 10 51 dep agent 1853:1857 arg1 STAT3 1860:1864 STAT3 1860:1864 STAT3 1860:1864 Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). 35626143 10 51 dep agent 1853:1857 arg1 signaling 1875:1883 mTOR signaling 1870:1883 mTOR signaling 1870:1883 Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). 35626143 5 52 theme Mito-LND 797:804 arg1 treatment 806:814 Mito-LND treatment 797:814 Mito-LND treatment 797:814 Mito-HNK or Mito-LND treatment alone reduced tumor load by 56% and 48%, respectively, whereas the combination of Mito-HNK and Mito-LND reduced tumor load by 83%. 35626143 2 53 theme mitochondrial 250:262 arg1 I 272:272 mitochondrial complex I 250:272 mitochondrial complex I 250:272 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 4 54 theme serum 704:708 arg1 levels 710:715 serum levels 704:715 serum levels of alanine aminotransferase and aspartate aminotransferase enzymes 704:782 No evidence of toxicity (including liver toxicity) was detected by monitoring serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. 35626143 10 55 theme unique 1829:1834 arg1 targets 1836:1842 unique targets 1829:1842 common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling) 1775:1884 Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). 35626143 2 56 theme STAT3 278:282 arg1 phosphorylation 284:298 STAT3 phosphorylation 278:298 STAT3 phosphorylation 278:298 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 5 57 dep reduced 822:828 arg1 whereas 871:877 whereas 871:877 whereas 871:877 Mito-HNK or Mito-LND treatment alone reduced tumor load by 56% and 48%, respectively, whereas the combination of Mito-HNK and Mito-LND reduced tumor load by 83%. 35626143 0 58 theme Compounds 75:83 arg1 Combination 38:48 a Combination 36:48 a Combination of Mitochondria-Targeted Compounds 36:83 Chemoprevention of Lung Cancer with a Combination of Mitochondria-Targeted Compounds. 35626143 2 59 theme I 272:272 arg1 honokiol 213:220 mitochondria-targeted honokiol 191:220 mitochondria-targeted honokiol (Mito-HNK) 191:231 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 59 theme I 272:272 arg1 inhibitor 237:245 an inhibitor 234:245 an inhibitor of mitochondrial complex I and STAT3 phosphorylation 234:298 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 1 60 theme lung 156:159 arg1 chemoprevention 168:182 lung cancer chemoprevention 156:182 lung cancer chemoprevention 156:182 Combined treatment targeting mitochondria may improve the efficacy of lung cancer chemoprevention. 35626143 9 61 from metabolism 1629:1638 arg1 cells 1654:1658 lung tumor cells 1643:1658 lung tumor cells 1643:1658 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 2 62 from efficacy 481:488 arg1 carcinogenesis 504:517 mouse lung carcinogenesis 493:517 mouse lung carcinogenesis 493:517 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 4 63 theme aspartate 749:757 arg1 aminotransferase 759:774 aspartate aminotransferase 749:774 aspartate aminotransferase 749:774 No evidence of toxicity (including liver toxicity) was detected by monitoring serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. 35626143 7 64 theme complex 1252:1258 arg1 ǀ 1260:1260 mitochondrial complex ǀ 1238:1260 mitochondrial complex ǀ 1238:1260 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 1 65 theme chemoprevention 168:182 arg1 efficacy 144:151 the efficacy 140:151 the efficacy of lung cancer chemoprevention 140:182 Combined treatment targeting mitochondria may improve the efficacy of lung cancer chemoprevention. 35626143 6 66 theme single-cell 1038:1048 arg1 sequencing 1054:1063 single-cell RNA sequencing 1038:1063 single-cell RNA sequencing 1038:1063 To understand the potential mechanism(s) of action for the observed combinatorial effects, single-cell RNA sequencing was performed using mouse tumors treated with Mito-HNK, Mito-LND, and their combination. 35626143 9 67 theme N-glycan 1591:1598 arg1 biosynthesis 1600:1611 N-glycan biosynthesis 1591:1611 N-glycan biosynthesis 1591:1611 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 9 68 from biosynthesis 1600:1611 arg1 cells 1654:1658 lung tumor cells 1643:1658 lung tumor cells 1643:1658 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 9 69 dep arginine 1558:1565 arg1 metabolism 1629:1638 tryptophan metabolism 1618:1638 tryptophan metabolism 1618:1638 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 9 69 dep arginine 1558:1565 arg1 metabolism 1579:1588 metabolism 1579:1588 metabolism 1579:1588 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 9 69 dep arginine 1558:1565 arg1 biosynthesis 1600:1611 N-glycan biosynthesis 1591:1611 N-glycan biosynthesis 1591:1611 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 5 70 theme tumor 830:834 arg1 load 836:839 tumor load 830:839 tumor load 830:839 Mito-HNK or Mito-LND treatment alone reduced tumor load by 56% and 48%, respectively, whereas the combination of Mito-HNK and Mito-LND reduced tumor load by 83%. 35626143 10 71 theme antitumor 1712:1720 arg1 efficacy 1722:1729 the antitumor efficacy 1708:1729 the antitumor efficacy of Mito-HNK 1708:1741 Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). 35626143 9 72 theme tryptophan 1618:1627 arg1 metabolism 1629:1638 tryptophan metabolism 1618:1638 tryptophan metabolism 1618:1638 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 2 73 theme AKT/mTOR/p70S6K 399:413 arg1 complexes 380:388 mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling 366:423 mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling 366:423 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 2 73 theme AKT/mTOR/p70S6K 399:413 arg1 signaling 415:423 AKT/mTOR/p70S6K signaling 399:423 AKT/mTOR/p70S6K signaling 399:423 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 0 74 theme Cancer 24:29 arg1 Chemoprevention 0:14 Chemoprevention 0:14 Chemoprevention of Lung Cancer with a Combination of Mitochondria-Targeted Compounds. 0:84 Chemoprevention of Lung Cancer with a Combination of Mitochondria-Targeted Compounds. 35626143 2 75 theme chemopreventive 465:479 arg1 efficacy 481:488 their combinational chemopreventive efficacy 445:488 their combinational chemopreventive efficacy on mouse lung carcinogenesis 445:517 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 11 76 theme cancer 1983:1988 arg1 chemoprevention 1990:2004 lung cancer chemoprevention 1978:2004 lung cancer chemoprevention 1978:2004 Therefore, the combination of Mito-HNK with Mito-LND may present an effective strategy for lung cancer chemoprevention. 35626143 7 77 theme Mito-HNK 1175:1182 arg1 treatment 1184:1192 Mito-HNK treatment 1175:1192 Mito-HNK treatment 1175:1192 In lung tumor cells, Mito-HNK treatment blocked the expression of genes involved in mitochondrial complex ǀ, oxidative phosphorylation, glycolysis, and STAT3 signaling. 35626143 9 78 theme tumor 1648:1652 arg1 cells 1654:1658 lung tumor cells 1643:1658 lung tumor cells 1643:1658 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 6 79 theme mouse 1085:1089 arg1 tumors 1091:1096 mouse tumors 1085:1096 mouse tumors treated with Mito-HNK, Mito-LND, and their combination 1085:1151 To understand the potential mechanism(s) of action for the observed combinatorial effects, single-cell RNA sequencing was performed using mouse tumors treated with Mito-HNK, Mito-LND, and their combination. 35626143 9 80 with combination 1510:1520 arg1 Mito-LND 1539:1546 Mito-LND 1539:1546 Mito-LND 1539:1546 In addition to these changes, a combination of Mito-HNK with Mito-LND decreased arginine and proline metabolism, N-glycan biosynthesis, and tryptophan metabolism in lung tumor cells. 35626143 5 81 theme Mito-LND 911:918 arg1 combination 883:893 the combination 879:893 the combination of Mito-HNK and Mito-LND 879:918 Mito-HNK or Mito-LND treatment alone reduced tumor load by 56% and 48%, respectively, whereas the combination of Mito-HNK and Mito-LND reduced tumor load by 83%. 35626143 2 82 theme lung 499:502 arg1 carcinogenesis 504:517 mouse lung carcinogenesis 493:517 mouse lung carcinogenesis 493:517 Here, mitochondria-targeted honokiol (Mito-HNK), an inhibitor of mitochondrial complex I and STAT3 phosphorylation, and mitochondria-targeted lonidamine (Mito-LND), an inhibitor of mitochondrial complexes I/II and AKT/mTOR/p70S6K signaling, were evaluated for their combinational chemopreventive efficacy on mouse lung carcinogenesis. 35626143 8 83 theme lung 1460:1463 arg1 cells 1471:1475 lung tumor cells 1460:1475 lung tumor cells 1460:1475 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 3 84 theme one-week 557:564 arg1 treatment 582:590 one-week post-carcinogen treatment 557:590 one-week post-carcinogen treatment 557:590 All chemopreventive treatments began one-week post-carcinogen treatment and continued daily for 24 weeks. 35626143 8 85 dep complexes 1384:1392 arg1 signaling 1447:1455 AKT/mTOR/p70S6K signaling 1431:1455 AKT/mTOR/p70S6K signaling 1431:1455 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 8 85 dep complexes 1384:1392 arg1 I/II 1394:1397 I/II 1394:1397 I/II 1394:1397 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 8 85 dep complexes 1384:1392 arg1 phosphorylation 1410:1424 oxidative phosphorylation 1400:1424 oxidative phosphorylation 1400:1424 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 8 85 dep complexes 1384:1392 arg1 complexes 1384:1392 mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling 1370:1455 mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling 1370:1455 Mito-LND inhibited the expression of genes for mitochondrial complexes I/II, oxidative phosphorylation, and AKT/mTOR/p70S6K signaling in lung tumor cells. 35626143 11 86 theme effective 1955:1963 arg1 strategy 1965:1972 an effective strategy 1952:1972 an effective strategy for lung cancer chemoprevention 1952:2004 Therefore, the combination of Mito-HNK with Mito-LND may present an effective strategy for lung cancer chemoprevention. 35626143 10 87 theme oxidative 1791:1799 arg1 targets 1782:1788 common targets 1775:1788 common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling) 1775:1884 Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). 35626143 10 87 theme oxidative 1791:1799 arg1 phosphorylation 1801:1815 oxidative phosphorylation 1791:1815 oxidative phosphorylation 1791:1815 Our results demonstrate that Mito-LND enhanced the antitumor efficacy of Mito-HNK, where both compounds inhibited common targets (oxidative phosphorylation) as well as unique targets for each agent (STAT3 and mTOR signaling). 37335061 7 0 dep N-339 987:991 arg1 refer 994:998 refer 994:998 refer to Hxb2 994:1006 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 1 1 theme genotypes 210:218 arg1 genotypes 210:218 the most important genotypes 191:218 the most important genotypes in China 191:227 HIV-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). 37335061 1 1 theme genotypes 210:218 arg1 one 184:186 one 184:186 one 184:186 HIV-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). 37335061 6 2 theme CDS 873:875 arg1 sites 891:895 The N-linked CDS glycosylation sites 860:895 The N-linked CDS glycosylation sites for gp120 in CRF01_AE 860:917 The N-linked CDS glycosylation sites for gp120 in CRF01_AE were analyzed. 37335061 6 3 from sites 891:895 arg1 CRF01_AE 910:917 CRF01_AE 910:917 CRF01_AE 910:917 The N-linked CDS glycosylation sites for gp120 in CRF01_AE were analyzed. 37335061 4 4 theme CRF01_AE 568:575 arg1 gene 560:563 the envelope protein (env) gene 533:563 the envelope protein (env) gene of CRF01_AE in China and Thailand 533:597 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 8 5 from Thailand 1133:1140 arg1 group 1122:1126 the MSM group 1114:1126 the MSM group from Thailand 1114:1140 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 8 6 theme widespread 1214:1223 arg1 genotype 1234:1241 the widespread CRF01_AE genotype 1210:1241 the widespread CRF01_AE genotype in MSM 1210:1248 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 8 7 theme site 1187:1190 arg1 N-339 1192:1196 the hyper-glycosylation site N-339 1163:1196 the hyper-glycosylation site N-339 1163:1196 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 5 8 from transmission 741:752 arg1 populations 770:780 populations 770:780 populations 770:780 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 8 from transmission 741:752 arg1 HCs 845:847 HCs 845:847 HCs 845:847 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 8 from transmission 741:752 arg1 IDUs 815:818 IDUs 815:818 IDUs 815:818 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 8 from transmission 741:752 arg1 variety 759:765 a variety 757:765 a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM 757:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 8 from transmission 741:752 arg1 MSM 855:857 MSM 855:857 MSM 855:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 8 from transmission 741:752 arg1 users 808:812 intravenous drug users 791:812 intravenous drug users (IDUs) 791:819 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 8 from transmission 741:752 arg1 contacts 835:842 heterosexual contacts 822:842 heterosexual contacts (HCs) 822:848 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 4 9 theme HIV 634:636 arg1 database 638:645 the Los Alamos HIV database 619:645 the Los Alamos HIV database 619:645 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 0 10 with sex 130:132 arg1 men 139:141 men 139:141 men 139:141 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 1 11 contain have 270:273 arg1 men 262:264 men 262:264 men who have sex with men (MSM) 262:292 HIV-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). 37335061 1 11 contain have 270:273 arg2 sex 275:277 sex 275:277 sex 275:277 HIV-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). 37335061 7 12 from N-339 987:991 arg1 gp120 1016:1020 the gp120 1012:1020 the gp120 of CRF01_AE in MSM 1012:1039 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 7 13 from China 1080:1084 arg1 groups 1068:1073 the IDU and HC groups 1053:1073 groups 1068:1073 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 0 14 link N-linked 19:26 arg1 site 28:31 Hyper-glycosylated N-linked site 339 0:35 Hyper-glycosylated N-linked site 339 of gp120 0:44 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 0 14 link N-linked 19:26 arg1 gp120 40:44 gp120 40:44 gp120 40:44 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 5 15 dep such 783:786 arg1 as 788:789 as 788:789 as 788:789 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 4 16 theme DNA 497:499 arg1 CDSs 512:515 CDSs 512:515 CDSs 512:515 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 4 16 theme DNA 497:499 arg1 sequences 501:509 the complete DNA sequences 484:509 the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand 484:597 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 7 17 theme HC 1065:1066 arg1 groups 1068:1073 the IDU and HC groups 1053:1073 groups 1068:1073 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 3 18 from predominance 441:452 arg1 MSM 457:459 MSM 457:459 MSM 457:459 Describing the variant characterization of CRF01_AE will help to reveal the reason behind its predominance in MSM. 37335061 5 19 theme risk 718:721 arg1 factors 723:729 the risk factors 714:729 the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM 714:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 0 20 theme CRF01_AE 89:96 arg1 transmission 98:109 CRF01_AE transmission 89:109 CRF01_AE transmission among men who have sex with men in China and Thailand 89:163 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 4 21 theme complete 488:495 arg1 CDSs 512:515 CDSs 512:515 CDSs 512:515 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 4 21 theme complete 488:495 arg1 sequences 501:509 the complete DNA sequences 484:509 the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand 484:597 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 8 22 from same 1106:1109 arg1 group 1122:1126 the MSM group 1114:1126 the MSM group from Thailand 1114:1140 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 8 23 theme MSM 1118:1120 arg1 group 1122:1126 the MSM group 1114:1126 the MSM group from Thailand 1114:1140 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 3 24 theme variant 362:368 arg1 characterization 370:385 the variant characterization 358:385 the variant characterization of CRF01_AE 358:397 Describing the variant characterization of CRF01_AE will help to reveal the reason behind its predominance in MSM. 37335061 0 25 theme N-linked 19:26 arg1 site 28:31 Hyper-glycosylated N-linked site 339 0:35 Hyper-glycosylated N-linked site 339 of gp120 0:44 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 0 25 theme N-linked 19:26 arg1 gp120 40:44 gp120 40:44 gp120 40:44 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 6 26 link N-linked 864:871 arg1 sites 891:895 The N-linked CDS glycosylation sites 860:895 The N-linked CDS glycosylation sites for gp120 in CRF01_AE 860:917 The N-linked CDS glycosylation sites for gp120 in CRF01_AE were analyzed. 37335061 8 27 from genotype 1234:1241 arg1 MSM 1246:1248 MSM 1246:1248 MSM 1246:1248 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 3 28 dep reason 423:428 arg1 behind 430:435 behind 430:435 behind its predominance in MSM 430:459 Describing the variant characterization of CRF01_AE will help to reveal the reason behind its predominance in MSM. 37335061 0 29 theme Hyper-glycosylated 0:17 arg1 site 28:31 Hyper-glycosylated N-linked site 339 0:35 Hyper-glycosylated N-linked site 339 of gp120 0:44 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 0 29 theme Hyper-glycosylated 0:17 arg1 gp120 40:44 gp120 40:44 gp120 40:44 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 4 30 theme present 469:475 arg1 study 477:481 the present study 465:481 the present study 465:481 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 7 31 theme hyper-glycosylation 962:980 arg1 N-339 987:991 a unique hyper-glycosylation site N-339 953:991 a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM 953:1039 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 5 32 theme intravenous 791:801 arg1 IDUs 815:818 IDUs 815:818 IDUs 815:818 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 32 theme intravenous 791:801 arg1 users 808:812 intravenous drug users 791:812 intravenous drug users (IDUs) 791:819 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 33 theme HIV-1 735:739 arg1 transmission 741:752 HIV-1 transmission 735:752 HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM 735:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 4 34 theme Los 623:625 arg1 database 638:645 the Los Alamos HIV database 619:645 the Los Alamos HIV database 619:645 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 0 35 contain have 125:128 arg1 men 117:119 men 117:119 men who have sex with men in China and Thailand 117:163 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 0 35 contain have 125:128 arg2 sex 130:132 sex 130:132 sex with men 130:141 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 3 36 theme CRF01_AE 390:397 arg1 characterization 370:385 the variant characterization 358:385 the variant characterization of CRF01_AE 358:397 Describing the variant characterization of CRF01_AE will help to reveal the reason behind its predominance in MSM. 37335061 7 37 dep showed 946:951 arg1 compared 1041:1048 compared 1041:1048 showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China 946:1084 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 8 38 dep same 1106:1109 arg1 suggests 1149:1156 suggests 1149:1156 suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM 1149:1248 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 8 38 dep same 1106:1109 arg1 result 1091:1096 The result 1087:1096 The result 1087:1096 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 8 38 dep same 1106:1109 arg1 same 1106:1109 same 1106:1109 same 1106:1109 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 7 39 from MSM 1037:1039 arg1 gp120 1016:1020 the gp120 1012:1020 the gp120 of CRF01_AE in MSM 1012:1039 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 5 40 theme users 808:812 arg1 populations 770:780 populations 770:780 populations 770:780 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 40 theme users 808:812 arg1 HCs 845:847 HCs 845:847 HCs 845:847 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 40 theme users 808:812 arg1 IDUs 815:818 IDUs 815:818 IDUs 815:818 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 40 theme users 808:812 arg1 variety 759:765 a variety 757:765 a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM 757:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 40 theme users 808:812 arg1 MSM 855:857 MSM 855:857 MSM 855:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 40 theme users 808:812 arg1 users 808:812 intravenous drug users 791:812 intravenous drug users (IDUs) 791:819 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 40 theme users 808:812 arg1 contacts 835:842 heterosexual contacts 822:842 heterosexual contacts (HCs) 822:848 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 6 41 theme N-linked 864:871 arg1 sites 891:895 The N-linked CDS glycosylation sites 860:895 The N-linked CDS glycosylation sites for gp120 in CRF01_AE 860:917 The N-linked CDS glycosylation sites for gp120 in CRF01_AE were analyzed. 37335061 0 42 theme gp120 40:44 arg1 site 28:31 Hyper-glycosylated N-linked site 339 0:35 Hyper-glycosylated N-linked site 339 of gp120 0:44 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 0 42 theme gp120 40:44 arg1 gp120 40:44 gp120 40:44 gp120 40:44 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 1 43 from genotypes 210:218 arg1 China 223:227 China 223:227 China 223:227 HIV-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). 37335061 0 44 gly Hyper-glycosylated 0:17 arg1 site 28:31 Hyper-glycosylated N-linked site 339 0:35 Hyper-glycosylated N-linked site 339 of gp120 0:44 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 0 44 gly Hyper-glycosylated 0:17 arg1 gp120 40:44 gp120 40:44 gp120 40:44 Hyper-glycosylated N-linked site 339 of gp120 appears to be unique and may contribute to CRF01_AE transmission among men who have sex with men in China and Thailand. 37335061 6 45 theme glycosylation 877:889 arg1 sites 891:895 The N-linked CDS glycosylation sites 860:895 The N-linked CDS glycosylation sites for gp120 in CRF01_AE 860:917 The N-linked CDS glycosylation sites for gp120 in CRF01_AE were analyzed. 37335061 4 46 theme envelope 537:544 arg1 env 555:557 env 555:557 env 555:557 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 4 46 theme envelope 537:544 arg1 protein 546:552 envelope protein 537:552 the envelope protein (env) gene of CRF01_AE in China and Thailand 533:597 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 7 47 theme site 982:985 arg1 N-339 987:991 a unique hyper-glycosylation site N-339 953:991 a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM 953:1039 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 7 48 gly hyper-glycosylation 962:980 arg2 site 982:985 a unique hyper-glycosylation site N-339 953:991 a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM 953:1039 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 7 48 gly hyper-glycosylation 962:980 arg2 N-339 987:991 a unique hyper-glycosylation site N-339 953:991 a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM 953:1039 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 2 49 theme prevalent 318:326 arg1 strain 328:333 the most prevalent strain 309:333 the most prevalent strain among them 309:344 It has become the most prevalent strain among them. 37335061 1 50 theme men 262:264 arg1 population 248:257 the population 244:257 the population of men who have sex with men (MSM) 244:292 HIV-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). 37335061 8 51 theme CRF01_AE 1225:1232 arg1 genotype 1234:1241 the widespread CRF01_AE genotype 1210:1241 the widespread CRF01_AE genotype in MSM 1210:1248 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 8 52 theme hyper-glycosylation 1167:1185 arg1 N-339 1192:1196 the hyper-glycosylation site N-339 1163:1196 the hyper-glycosylation site N-339 1163:1196 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 1 53 from one 184:186 arg1 population 248:257 the population 244:257 the population of men who have sex with men (MSM) 244:292 HIV-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). 37335061 4 54 dep Los 623:625 arg1 Alamos 627:632 Alamos 627:632 Alamos 627:632 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 7 55 theme unique 955:960 arg1 N-339 987:991 a unique hyper-glycosylation site N-339 953:991 a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM 953:1039 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 7 56 from gp120 1016:1020 arg1 MSM 1037:1039 MSM 1037:1039 MSM 1037:1039 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 5 57 theme MSM 855:857 arg1 populations 770:780 populations 770:780 populations 770:780 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 57 theme MSM 855:857 arg1 HCs 845:847 HCs 845:847 HCs 845:847 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 57 theme MSM 855:857 arg1 IDUs 815:818 IDUs 815:818 IDUs 815:818 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 57 theme MSM 855:857 arg1 variety 759:765 a variety 757:765 a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM 757:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 57 theme MSM 855:857 arg1 MSM 855:857 MSM 855:857 MSM 855:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 57 theme MSM 855:857 arg1 users 808:812 intravenous drug users 791:812 intravenous drug users (IDUs) 791:819 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 57 theme MSM 855:857 arg1 contacts 835:842 heterosexual contacts 822:842 heterosexual contacts (HCs) 822:848 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 58 theme populations 770:780 arg1 populations 770:780 populations 770:780 populations 770:780 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 58 theme populations 770:780 arg1 HCs 845:847 HCs 845:847 HCs 845:847 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 58 theme populations 770:780 arg1 IDUs 815:818 IDUs 815:818 IDUs 815:818 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 58 theme populations 770:780 arg1 variety 759:765 a variety 757:765 a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM 757:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 58 theme populations 770:780 arg1 MSM 855:857 MSM 855:857 MSM 855:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 58 theme populations 770:780 arg1 users 808:812 intravenous drug users 791:812 intravenous drug users (IDUs) 791:819 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 58 theme populations 770:780 arg1 contacts 835:842 heterosexual contacts 822:842 heterosexual contacts (HCs) 822:848 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 8 59 from group 1122:1126 arg1 suggests 1149:1156 suggests 1149:1156 suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM 1149:1248 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 8 59 from group 1122:1126 arg1 result 1091:1096 The result 1087:1096 The result 1087:1096 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 8 59 from group 1122:1126 arg1 same 1106:1109 same 1106:1109 same 1106:1109 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 6 60 gly glycosylation 877:889 arg2 sites 891:895 The N-linked CDS glycosylation sites 860:895 The N-linked CDS glycosylation sites for gp120 in CRF01_AE 860:917 The N-linked CDS glycosylation sites for gp120 in CRF01_AE were analyzed. 37335061 5 61 theme heterosexual 822:833 arg1 HCs 845:847 HCs 845:847 HCs 845:847 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 61 theme heterosexual 822:833 arg1 contacts 835:842 heterosexual contacts 822:842 heterosexual contacts (HCs) 822:848 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 7 62 theme IDU 1057:1059 arg1 groups 1068:1073 the IDU and HC groups 1053:1073 groups 1068:1073 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 5 63 theme drug 803:806 arg1 IDUs 815:818 IDUs 815:818 IDUs 815:818 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 63 theme drug 803:806 arg1 users 808:812 intravenous drug users 791:812 intravenous drug users (IDUs) 791:819 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 7 64 from CRF01_AE 1025:1032 arg1 MSM 1037:1039 MSM 1037:1039 MSM 1037:1039 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 5 65 theme contacts 835:842 arg1 populations 770:780 populations 770:780 populations 770:780 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 65 theme contacts 835:842 arg1 HCs 845:847 HCs 845:847 HCs 845:847 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 65 theme contacts 835:842 arg1 IDUs 815:818 IDUs 815:818 IDUs 815:818 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 65 theme contacts 835:842 arg1 variety 759:765 a variety 757:765 a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM 757:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 65 theme contacts 835:842 arg1 MSM 855:857 MSM 855:857 MSM 855:857 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 65 theme contacts 835:842 arg1 users 808:812 intravenous drug users 791:812 intravenous drug users (IDUs) 791:819 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 5 65 theme contacts 835:842 arg1 contacts 835:842 heterosexual contacts 822:842 heterosexual contacts (HCs) 822:848 The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDUs), heterosexual contacts (HCs), and MSM. 37335061 7 66 theme CRF01_AE 1025:1032 arg1 gp120 1016:1020 the gp120 1012:1020 the gp120 of CRF01_AE in MSM 1012:1039 The results showed a unique hyper-glycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared to the IDU and HC groups from China. 37335061 4 67 from gene 560:563 arg1 CDSs 512:515 CDSs 512:515 CDSs 512:515 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 4 67 from gene 560:563 arg1 sequences 501:509 the complete DNA sequences 484:509 the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand 484:597 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 4 67 from gene 560:563 arg1 Thailand 590:597 Thailand 590:597 Thailand 590:597 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 4 67 from gene 560:563 arg1 China 580:584 China 580:584 China 580:584 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 1 68 theme HIV-1 166:170 arg1 CRF01_AE 172:179 HIV-1 CRF01_AE 166:179 HIV-1 CRF01_AE 166:179 HIV-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). 37335061 4 69 theme protein 546:552 arg1 gene 560:563 the envelope protein (env) gene 533:563 the envelope protein (env) gene of CRF01_AE in China and Thailand 533:597 In the present study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. 37335061 8 70 gly hyper-glycosylation 1167:1185 arg2 N-339 1192:1196 the hyper-glycosylation site N-339 1163:1196 the hyper-glycosylation site N-339 1163:1196 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 8 70 gly hyper-glycosylation 1167:1185 arg2 site 1187:1190 the hyper-glycosylation site N-339 1163:1196 the hyper-glycosylation site N-339 1163:1196 The result was the same in the MSM group from Thailand, which suggests that the hyper-glycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM. 37335061 1 71 theme important 200:208 arg1 genotypes 210:218 the most important genotypes 191:218 the most important genotypes in China 191:227 HIV-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). 37002018 2 0 theme mechanistic 505:515 arg1 basis 517:521 the mechanistic basis 501:521 the mechanistic basis for β-galactosylation in fission yeast 501:560 The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. 37002018 1 1 link α1,3-linked 307:317 arg1 Gal 319:321 α1,3-linked Gal 307:321 α1,3-linked Gal 307:321 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 6 2 theme suitable 1411:1418 arg1 substrates 1400:1409 donor and acceptor substrates 1381:1409 donor and acceptor substrates suitable for β-(1 → 3) bond formation 1381:1447 Docking simulations further indicated that Pvg3 can recognize donor and acceptor substrates suitable for β-(1 → 3) bond formation. 37002018 1 3 theme fission 190:196 arg1 yeast 198:202 the fission yeast 186:202 the fission yeast Schizosaccharomyces pombe 186:228 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 8 4 theme supporting 1647:1656 arg1 role 1658:1661 the supporting role 1643:1661 the supporting role of Pvg5 in PvGalβ biosynthesis 1643:1692 Collectively, these results provide insight into β-galactosylation catalyzed by Pvg3 and the supporting role of Pvg5 in PvGalβ biosynthesis. 37002018 0 5 theme pyruvylated 100:110 arg1 β1,3-galactose 112:125 pyruvylated β1,3-galactose 100:125 pyruvylated β1,3-galactose of N-linked oligosaccharides 100:154 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 5 6 theme catalytic 1218:1226 arg1 activity 1228:1235 catalytic activity in vivo 1218:1243 catalytic activity in vivo 1218:1243 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 5 7 theme type 1286:1289 arg1 β1,3-galactosyltransferase 1291:1316 a GT-A type β1,3-galactosyltransferase 1279:1316 a GT-A type β1,3-galactosyltransferase 1279:1316 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 5 7 theme type 1286:1289 arg1 Pvg3 1271:1274 Pvg3 1271:1274 Pvg3 1271:1274 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 5 8 theme GT31 1154:1157 arg1 motif 1170:1174 the GT31 family DXD motif 1150:1174 the GT31 family DXD motif 1150:1174 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 2 9 theme fission 548:554 arg1 yeast 556:560 fission yeast 548:560 fission yeast 548:560 The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. 37002018 1 10 from oligosaccharides 166:181 arg1 yeast 198:202 the fission yeast 186:202 the fission yeast Schizosaccharomyces pombe 186:228 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 3 11 dep biosynthesis 702:713 arg1 pvg3 722:725 pvg3 722:725 pvg3 722:725 To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. 37002018 3 11 dep biosynthesis 702:713 arg1 pvg5 732:735 pvg5 732:735 pvg5 732:735 To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. 37002018 3 11 dep biosynthesis 702:713 arg1 pvg2 716:719 pvg2 716:719 pvg2 716:719 To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. 37002018 1 12 theme non-reducing 378:389 arg1 end 391:393 the non-reducing end 374:393 the non-reducing end 374:393 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 5 13 theme family 1159:1164 arg1 motif 1170:1174 the GT31 family DXD motif 1150:1174 the GT31 family DXD motif 1150:1174 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 0 14 theme β1,3-galactose 112:125 arg1 biosynthesis 84:95 the biosynthesis 80:95 the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides 80:154 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 5 15 from Mutation 1138:1145 arg1 Pvg3 1193:1196 Pvg3 1193:1196 Pvg3 1193:1196 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 4 16 theme pvg5+ 986:990 arg1 presence 965:972 the presence 961:972 the presence of pvg2+ or pvg5+ 961:990 Fluorescent microscopy revealed that Pvg3 is stably localized at the Golgi membrane, regardless of the presence of pvg2+ or pvg5+, suggesting that Pvg2 and Pvg5 are essential for the function of Pvg3 as a β1,3-galactosyltransferase, and not for its localization to the Golgi. 37002018 1 17 from end 391:393 arg1 PvGalβ 363:368 PvGalβ 363:368 PvGalβ 363:368 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 17 from end 391:393 arg1 Gal 358:360 pyruvylated β1,3-linked Gal 334:360 pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end 334:393 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 0 18 link N-linked 130:137 arg1 oligosaccharides 139:154 N-linked oligosaccharides 130:154 N-linked oligosaccharides 130:154 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 2 19 theme PvGalβ 400:405 arg1 unit 407:410 The PvGalβ unit 396:410 The PvGalβ unit of N-glycans 396:423 The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. 37002018 2 19 theme PvGalβ 400:405 arg1 important 428:436 important 428:436 important 428:436 The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. 37002018 0 20 theme Mechanistic 0:10 arg1 insights 12:19 Mechanistic insights 0:19 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 0:155 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 3 21 from focus 746:750 arg1 pvg3 755:758 pvg3 755:758 pvg3 755:758 To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. 37002018 3 22 theme PvGalβ 695:700 arg1 biosynthesis 702:713 PvGalβ biosynthesis 695:713 PvGalβ biosynthesis (pvg2, pvg3, and pvg5) 695:736 To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. 37002018 4 23 theme Pvg3 1057:1060 arg1 function 1045:1052 the function 1041:1052 the function of Pvg3 as a β1,3-galactosyltransferase 1041:1092 Fluorescent microscopy revealed that Pvg3 is stably localized at the Golgi membrane, regardless of the presence of pvg2+ or pvg5+, suggesting that Pvg2 and Pvg5 are essential for the function of Pvg3 as a β1,3-galactosyltransferase, and not for its localization to the Golgi. 37002018 0 24 theme Schizosaccharomyces 26:44 arg1 Pvg3 72:75 Schizosaccharomyces pombe GT-A family protein Pvg3 26:75 Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides 26:154 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 1 25 theme α1,3-linked 307:317 arg1 Gal 319:321 α1,3-linked Gal 307:321 α1,3-linked Gal 307:321 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 0 26 theme oligosaccharides 139:154 arg1 β1,3-galactose 112:125 pyruvylated β1,3-galactose 100:125 pyruvylated β1,3-galactose of N-linked oligosaccharides 100:154 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 8 27 from role 1658:1661 arg1 biosynthesis 1681:1692 PvGalβ biosynthesis 1674:1692 PvGalβ biosynthesis 1674:1692 Collectively, these results provide insight into β-galactosylation catalyzed by Pvg3 and the supporting role of Pvg5 in PvGalβ biosynthesis. 37002018 8 28 theme PvGalβ 1674:1679 arg1 biosynthesis 1681:1692 PvGalβ biosynthesis 1674:1692 PvGalβ biosynthesis 1674:1692 Collectively, these results provide insight into β-galactosylation catalyzed by Pvg3 and the supporting role of Pvg5 in PvGalβ biosynthesis. 37002018 1 29 theme large 238:242 arg1 amounts 244:250 large amounts 238:250 large amounts 238:250 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 29 theme large 238:242 arg1 Gal 268:270 Gal 268:270 Gal 268:270 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 29 theme large 238:242 arg1 d-galactose 255:265 d-galactose 255:265 d-galactose 255:265 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 0 30 theme N-linked 130:137 arg1 oligosaccharides 139:154 N-linked oligosaccharides 130:154 N-linked oligosaccharides 130:154 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 1 31 contain contain 230:236 arg2 d-galactose 255:265 d-galactose 255:265 d-galactose 255:265 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 31 contain contain 230:236 arg2 amounts 244:250 large amounts 238:250 large amounts 238:250 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 31 contain contain 230:236 arg2 Gal 268:270 Gal 268:270 Gal 268:270 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 31 contain contain 230:236 arg1 oligosaccharides 166:181 N-linked oligosaccharides 157:181 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe 157:228 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 6 32 theme bond 1434:1437 arg1 formation 1439:1447 β-(1 → 3) bond formation 1424:1447 β-(1 → 3) bond formation 1424:1447 Docking simulations further indicated that Pvg3 can recognize donor and acceptor substrates suitable for β-(1 → 3) bond formation. 37002018 5 33 theme activity 1228:1235 arg1 loss 1210:1213 loss 1210:1213 loss of catalytic activity in vivo 1210:1243 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 0 34 theme GT-A 52:55 arg1 Pvg3 72:75 Schizosaccharomyces pombe GT-A family protein Pvg3 26:75 Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides 26:154 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 6 35 theme acceptor 1391:1398 arg1 substrates 1400:1409 donor and acceptor substrates 1381:1409 donor and acceptor substrates suitable for β-(1 → 3) bond formation 1381:1447 Docking simulations further indicated that Pvg3 can recognize donor and acceptor substrates suitable for β-(1 → 3) bond formation. 37002018 4 36 located localized 914:922 arg1 membrane 937:944 the Golgi membrane 927:944 the Golgi membrane 927:944 Fluorescent microscopy revealed that Pvg3 is stably localized at the Golgi membrane, regardless of the presence of pvg2+ or pvg5+, suggesting that Pvg2 and Pvg5 are essential for the function of Pvg3 as a β1,3-galactosyltransferase, and not for its localization to the Golgi. 37002018 4 36 located localized 914:922 arg2 Pvg3 899:902 Pvg3 899:902 Pvg3 899:902 Fluorescent microscopy revealed that Pvg3 is stably localized at the Golgi membrane, regardless of the presence of pvg2+ or pvg5+, suggesting that Pvg2 and Pvg5 are essential for the function of Pvg3 as a β1,3-galactosyltransferase, and not for its localization to the Golgi. 37002018 4 37 theme pvg2+ 977:981 arg1 presence 965:972 the presence 961:972 the presence of pvg2+ or pvg5+ 961:990 Fluorescent microscopy revealed that Pvg3 is stably localized at the Golgi membrane, regardless of the presence of pvg2+ or pvg5+, suggesting that Pvg2 and Pvg5 are essential for the function of Pvg3 as a β1,3-galactosyltransferase, and not for its localization to the Golgi. 37002018 7 38 theme two-hybrid 1456:1465 arg1 assay 1467:1471 Yeast two-hybrid assay 1450:1471 Yeast two-hybrid assay 1450:1471 Yeast two-hybrid assay showed that Pvg5 physically interacts with Pvg3 and the pyruvyltransferase Pvg1. 37002018 2 39 theme nonsexual 453:461 arg1 flocculation 463:474 nonsexual flocculation 453:474 nonsexual flocculation 453:474 The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. 37002018 1 40 link β1,3-linked 346:356 arg1 PvGalβ 363:368 PvGalβ 363:368 PvGalβ 363:368 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 40 link β1,3-linked 346:356 arg1 Gal 358:360 pyruvylated β1,3-linked Gal 334:360 pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end 334:393 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 41 theme d-galactose 255:265 arg1 amounts 244:250 large amounts 238:250 large amounts 238:250 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 41 theme d-galactose 255:265 arg1 Gal 268:270 Gal 268:270 Gal 268:270 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 41 theme d-galactose 255:265 arg1 d-galactose 255:265 d-galactose 255:265 d-galactose 255:265 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 0 42 theme protein 64:70 arg1 Pvg3 72:75 Schizosaccharomyces pombe GT-A family protein Pvg3 26:75 Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides 26:154 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 1 43 theme pyruvylated 334:344 arg1 PvGalβ 363:368 PvGalβ 363:368 PvGalβ 363:368 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 43 theme pyruvylated 334:344 arg1 Gal 358:360 pyruvylated β1,3-linked Gal 334:360 pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end 334:393 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 8 44 from insight 1590:1596 arg1 biosynthesis 1681:1692 PvGalβ biosynthesis 1674:1692 PvGalβ biosynthesis 1674:1692 Collectively, these results provide insight into β-galactosylation catalyzed by Pvg3 and the supporting role of Pvg5 in PvGalβ biosynthesis. 37002018 0 45 from Pvg3 72:75 arg1 biosynthesis 84:95 the biosynthesis 80:95 the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides 80:154 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 1 46 dep yeast 198:202 arg1 pombe 224:228 Schizosaccharomyces pombe 204:228 the fission yeast Schizosaccharomyces pombe 186:228 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 6 47 theme donor 1381:1385 arg1 substrates 1400:1409 donor and acceptor substrates 1381:1409 donor and acceptor substrates suitable for β-(1 → 3) bond formation 1381:1447 Docking simulations further indicated that Pvg3 can recognize donor and acceptor substrates suitable for β-(1 → 3) bond formation. 37002018 0 48 theme family 57:62 arg1 Pvg3 72:75 Schizosaccharomyces pombe GT-A family protein Pvg3 26:75 Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides 26:154 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 1 49 theme β1,3-linked 346:356 arg1 PvGalβ 363:368 PvGalβ 363:368 PvGalβ 363:368 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 49 theme β1,3-linked 346:356 arg1 Gal 358:360 pyruvylated β1,3-linked Gal 334:360 pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end 334:393 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 1 50 link N-linked 157:164 arg1 oligosaccharides 166:181 N-linked oligosaccharides 157:181 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe 157:228 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 2 51 theme invasive 480:487 arg1 growth 489:494 invasive growth 480:494 invasive growth 480:494 The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. 37002018 6 52 theme β- 1424:1425 arg1 formation 1439:1447 β-(1 → 3) bond formation 1424:1447 β-(1 → 3) bond formation 1424:1447 Docking simulations further indicated that Pvg3 can recognize donor and acceptor substrates suitable for β-(1 → 3) bond formation. 37002018 8 53 theme Pvg5 1666:1669 arg1 role 1658:1661 the supporting role 1643:1661 the supporting role of Pvg5 in PvGalβ biosynthesis 1643:1692 Collectively, these results provide insight into β-galactosylation catalyzed by Pvg3 and the supporting role of Pvg5 in PvGalβ biosynthesis. 37002018 8 53 theme Pvg5 1666:1669 arg1 insight 1590:1596 insight 1590:1596 insight into β-galactosylation catalyzed by Pvg3 1590:1637 Collectively, these results provide insight into β-galactosylation catalyzed by Pvg3 and the supporting role of Pvg5 in PvGalβ biosynthesis. 37002018 2 54 from β-galactosylation 527:543 arg1 yeast 556:560 fission yeast 548:560 fission yeast 548:560 The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. 37002018 0 55 dep Schizosaccharomyces 26:44 arg1 pombe 46:50 pombe 46:50 pombe 46:50 Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated β1,3-galactose of N-linked oligosaccharides. 37002018 6 56 theme 1 → 3 1427:1431 arg1 formation 1439:1447 β-(1 → 3) bond formation 1424:1447 β-(1 → 3) bond formation 1424:1447 Docking simulations further indicated that Pvg3 can recognize donor and acceptor substrates suitable for β-(1 → 3) bond formation. 37002018 5 57 theme DXD 1166:1168 arg1 motif 1170:1174 the GT31 family DXD motif 1150:1174 the GT31 family DXD motif 1150:1174 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 1 58 theme N-linked 157:164 arg1 oligosaccharides 166:181 N-linked oligosaccharides 157:181 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe 157:228 N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. 37002018 3 59 theme galactosyltransferase 813:833 arg1 proteins 852:859 galactosyltransferase family 31 (GT31) proteins 813:859 galactosyltransferase family 31 (GT31) proteins 813:859 To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. 37002018 5 60 theme motif 1170:1174 arg1 Mutation 1138:1145 Mutation 1138:1145 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 1138:1196 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 7 61 theme pyruvyltransferase 1529:1546 arg1 Pvg1 1548:1551 the pyruvyltransferase Pvg1 1525:1551 the pyruvyltransferase Pvg1 1525:1551 Yeast two-hybrid assay showed that Pvg5 physically interacts with Pvg3 and the pyruvyltransferase Pvg1. 37002018 2 62 theme N-glycans 415:423 arg1 unit 407:410 The PvGalβ unit 396:410 The PvGalβ unit of N-glycans 396:423 The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. 37002018 2 62 theme N-glycans 415:423 arg1 important 428:436 important 428:436 important 428:436 The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. 37002018 3 63 contain contain 783:789 arg1 pvg3 755:758 pvg3 755:758 pvg3 755:758 To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. 37002018 3 63 contain contain 783:789 arg2 domain 793:798 a domain 791:798 a domain conserved in galactosyltransferase family 31 (GT31) proteins 791:859 To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. 37002018 4 64 theme Fluorescent 862:872 arg1 microscopy 874:883 Fluorescent microscopy 862:883 Fluorescent microscopy 862:883 Fluorescent microscopy revealed that Pvg3 is stably localized at the Golgi membrane, regardless of the presence of pvg2+ or pvg5+, suggesting that Pvg2 and Pvg5 are essential for the function of Pvg3 as a β1,3-galactosyltransferase, and not for its localization to the Golgi. 37002018 3 65 theme family 835:840 arg1 proteins 852:859 galactosyltransferase family 31 (GT31) proteins 813:859 galactosyltransferase family 31 (GT31) proteins 813:859 To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. 37002018 6 66 theme Docking 1319:1325 arg1 simulations 1327:1337 Docking simulations 1319:1337 Docking simulations 1319:1337 Docking simulations further indicated that Pvg3 can recognize donor and acceptor substrates suitable for β-(1 → 3) bond formation. 37002018 7 67 theme Yeast 1450:1454 arg1 assay 1467:1471 Yeast two-hybrid assay 1450:1471 Yeast two-hybrid assay 1450:1471 Yeast two-hybrid assay showed that Pvg5 physically interacts with Pvg3 and the pyruvyltransferase Pvg1. 37002018 5 68 theme GT-A 1281:1284 arg1 β1,3-galactosyltransferase 1291:1316 a GT-A type β1,3-galactosyltransferase 1279:1316 a GT-A type β1,3-galactosyltransferase 1279:1316 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 5 68 theme GT-A 1281:1284 arg1 Pvg3 1271:1274 Pvg3 1271:1274 Pvg3 1271:1274 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 4 69 theme Golgi 931:935 arg1 membrane 937:944 the Golgi membrane 927:944 the Golgi membrane 927:944 Fluorescent microscopy revealed that Pvg3 is stably localized at the Golgi membrane, regardless of the presence of pvg2+ or pvg5+, suggesting that Pvg2 and Pvg5 are essential for the function of Pvg3 as a β1,3-galactosyltransferase, and not for its localization to the Golgi. 37002018 5 70 theme fold 1185:1188 arg1 Mutation 1138:1145 Mutation 1138:1145 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 1138:1196 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 37002018 5 71 theme GT-A 1180:1183 arg1 fold 1185:1188 GT-A fold 1180:1188 GT-A fold 1180:1188 Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. 36754933 6 0 theme cell 893:896 arg1 glycoproteins 713:725 the enriched glycoproteins 700:725 the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling 700:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 0 theme cell 893:896 arg1 remodeling 903:912 cell wall remodeling 893:912 cell wall remodeling 893:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 10 1 theme Dio 1262:1264 arg1 B 1266:1266 Dio B 1262:1266 Dio B 1262:1266 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 2 2 theme A 318:318 arg1 chromatography 336:349 Concanavalin A lectin affinity chromatography 305:349 Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification 305:399 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 10 3 theme peptide 1251:1257 arg1 presence 1276:1283 the presence 1272:1283 the presence of non-canonical motif 1272:1306 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 10 3 theme peptide 1251:1257 arg1 Absence 1233:1239 Absence 1233:1239 Absence of signal peptide in Dio B 1233:1266 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 6 4 theme reticulum 863:871 arg1 control 881:887 endoplasmic reticulum quality control 851:887 endoplasmic reticulum quality control 851:887 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 4 theme reticulum 863:871 arg1 glycoproteins 713:725 the enriched glycoproteins 700:725 the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling 700:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 1 5 theme post 188:191 arg1 Glycosylation 158:170 Glycosylation 158:170 Glycosylation 158:170 Glycosylation is an important post translational modification in plants. 36754933 1 5 theme post 188:191 arg1 modification 207:218 an important post translational modification 175:218 an important post translational modification in plants 175:228 Glycosylation is an important post translational modification in plants. 36754933 8 6 theme N-glycosylated 1061:1074 arg1 form 1076:1079 the only N-glycosylated form 1052:1079 the only N-glycosylated form 1052:1079 Interestingly, out of the two dioscorin isoforms, Dio B was the only N-glycosylated form. 36754933 8 6 theme N-glycosylated 1061:1074 arg1 B 1046:1046 Dio B 1042:1046 Dio B 1042:1046 Interestingly, out of the two dioscorin isoforms, Dio B was the only N-glycosylated form. 36754933 6 7 theme Gene 656:659 arg1 Ontology 661:668 Gene Ontology 656:668 Gene Ontology 656:668 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 0 8 theme Proteins 128:135 arg1 Role 107:110 Central Role 99:110 Central Role of Glycosylated Proteins in Tuber Maturation 99:155 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 9 9 with similarity 1170:1179 arg1 sporamin 1186:1193 sporamin 1186:1193 sporamin 1186:1193 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 9 9 with similarity 1170:1179 arg1 protein 1208:1214 the storage protein 1196:1214 the storage protein of sweet potato 1196:1230 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 2 10 theme affinity 327:334 arg1 chromatography 336:349 Concanavalin A lectin affinity chromatography 305:349 Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification 305:399 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 2 11 gly glycosylated 258:269 arg1 proteins 271:278 N-linked glycosylated proteins 249:278 N-linked glycosylated proteins of Dioscorea alata 249:297 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 0 12 theme Tuber 140:144 arg1 Maturation 146:155 Tuber Maturation 140:155 Tuber Maturation 140:155 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 2 13 theme N-linked 249:256 arg1 proteins 271:278 N-linked glycosylated proteins 249:278 N-linked glycosylated proteins of Dioscorea alata 249:297 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 2 14 dep chromatography 336:349 arg1 enrichment 351:360 enrichment 351:360 Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification 305:399 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 9 15 theme In 1082:1083 arg1 analysis 1092:1099 In silico analysis 1082:1099 In silico analysis 1082:1099 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 10 16 from peptide 1251:1257 arg1 B 1266:1266 Dio B 1262:1266 Dio B 1262:1266 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 4 17 theme Signal 467:472 arg1 P 474:474 Signal P 467:474 Signal P 467:474 Signal P and sub-cellular localization showed 42.2% of proteins to be secretory. 36754933 2 18 theme Dioscorea 283:291 arg1 alata 293:297 Dioscorea alata 283:297 Dioscorea alata 283:297 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 7 19 gly glycoproteins 977:989 arg1 glycoproteins 977:989 the essential glycoproteins 963:989 the essential glycoproteins 963:989 This was supported by biochemical validation of the essential glycoproteins. 36754933 9 20 theme O-glycosylation 1108:1122 arg1 sites 1124:1128 O-glycosylation sites 1108:1128 O-glycosylation sites 1108:1128 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 0 21 theme Atypical 62:69 arg1 Glycosylation 71:83 Atypical Glycosylation 62:83 Atypical Glycosylation 62:83 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 2 22 theme proteins 271:278 arg1 analysis 237:244 First analysis 231:244 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification 231:399 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 6 23 dep glycoproteins 713:725 arg1 remodeling 903:912 cell wall remodeling 893:912 cell wall remodeling 893:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 23 dep glycoproteins 713:725 arg1 lignification 815:827 lignification 815:827 lignification 815:827 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 23 dep glycoproteins 713:725 arg1 control 881:887 endoplasmic reticulum quality control 851:887 endoplasmic reticulum quality control 851:887 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 23 dep glycoproteins 713:725 arg1 trafficking 838:848 protein trafficking 830:848 protein trafficking 830:848 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 23 dep glycoproteins 713:725 arg1 transduction 801:812 signal transduction 794:812 signal transduction 794:812 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 23 dep glycoproteins 713:725 arg1 glycoproteins 713:725 the enriched glycoproteins 700:725 the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling 700:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 0 24 from Role 107:110 arg1 Maturation 146:155 Tuber Maturation 140:155 Tuber Maturation 140:155 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 11 25 theme B 1400:1400 arg1 isoform 1402:1408 Dio B isoform 1396:1408 Dio B isoform 1396:1408 The analysis revealed that N-glycosylation of Dio B isoform maintains the activities associated with Dioscorin at maturity and provides an overview of protein N-glycosylation, enriching the glycoproteome database of plants especially tubers. 36754933 10 26 theme non-canonical 1288:1300 arg1 motif 1302:1306 non-canonical motif 1288:1306 non-canonical motif 1288:1306 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 0 27 theme Central 99:105 arg1 Role 107:110 Central Role 99:110 Central Role of Glycosylated Proteins in Tuber Maturation 99:155 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 3 28 gly glycoproteins 438:450 arg1 glycoproteins 438:450 114 enriched glycoproteins 425:450 114 enriched glycoproteins 425:450 In total, 114 enriched glycoproteins were detected. 36754933 6 29 theme tuber 769:773 arg1 maturation 775:784 tuber maturation 769:784 tuber maturation namely 769:791 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 9 30 dep In 1082:1083 arg1 silico 1085:1090 silico 1085:1090 silico 1085:1090 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 6 31 theme essential 755:763 arg1 processes 745:753 processes 745:753 processes essential for tuber maturation namely 745:791 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 0 32 theme N-Linked 0:7 arg1 Analysis 23:30 N-Linked Glycoproteome Analysis 0:30 N-Linked Glycoproteome Analysis of Diosorea alata Tuber 0:54 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 5 33 theme lipid 631:635 arg1 peroxidases 563:573 peroxidases 563:573 peroxidases 563:573 These included peroxidases, endochitinases, calreticulin, calnexin, thaumatins and lipid transfer proteins. 36754933 5 33 theme lipid 631:635 arg1 proteins 646:653 lipid transfer proteins 631:653 lipid transfer proteins 631:653 These included peroxidases, endochitinases, calreticulin, calnexin, thaumatins and lipid transfer proteins. 36754933 11 34 theme glycoproteome 1540:1552 arg1 database 1554:1561 the glycoproteome database 1536:1561 the glycoproteome database of plants 1536:1571 The analysis revealed that N-glycosylation of Dio B isoform maintains the activities associated with Dioscorin at maturity and provides an overview of protein N-glycosylation, enriching the glycoproteome database of plants especially tubers. 36754933 0 35 theme Diosorea 35:42 arg1 Tuber 50:54 Diosorea alata Tuber 35:54 Diosorea alata Tuber 35:54 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 0 36 theme Tuber 50:54 arg1 Analysis 23:30 N-Linked Glycoproteome Analysis 0:30 N-Linked Glycoproteome Analysis of Diosorea alata Tuber 0:54 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 9 37 theme storage 1200:1206 arg1 sporamin 1186:1193 sporamin 1186:1193 sporamin 1186:1193 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 9 37 theme storage 1200:1206 arg1 protein 1208:1214 the storage protein 1196:1214 the storage protein of sweet potato 1196:1230 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 10 38 theme signal 1244:1249 arg1 peptide 1251:1257 signal peptide 1244:1257 signal peptide in Dio B 1244:1266 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 6 39 theme signal 794:799 arg1 transduction 801:812 signal transduction 794:812 signal transduction 794:812 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 39 theme signal 794:799 arg1 glycoproteins 713:725 the enriched glycoproteins 700:725 the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling 700:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 8 40 theme Dio 1042:1044 arg1 form 1076:1079 the only N-glycosylated form 1052:1079 the only N-glycosylated form 1052:1079 Interestingly, out of the two dioscorin isoforms, Dio B was the only N-glycosylated form. 36754933 8 40 theme Dio 1042:1044 arg1 B 1046:1046 Dio B 1042:1046 Dio B 1042:1046 Interestingly, out of the two dioscorin isoforms, Dio B was the only N-glycosylated form. 36754933 6 41 theme Ontology 661:668 arg1 analysis 681:688 Gene Ontology and MapMan analysis 656:688 Gene Ontology and MapMan analysis 656:688 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 9 42 theme potato 1225:1230 arg1 sporamin 1186:1193 sporamin 1186:1193 sporamin 1186:1193 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 9 42 theme potato 1225:1230 arg1 protein 1208:1214 the storage protein 1196:1214 the storage protein of sweet potato 1196:1230 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 7 43 theme essential 967:975 arg1 glycoproteins 977:989 the essential glycoproteins 963:989 the essential glycoproteins 963:989 This was supported by biochemical validation of the essential glycoproteins. 36754933 2 44 theme lectin 320:325 arg1 chromatography 336:349 Concanavalin A lectin affinity chromatography 305:349 Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification 305:399 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 6 45 gly glycoproteins 713:725 arg1 remodeling 903:912 cell wall remodeling 893:912 cell wall remodeling 893:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 45 gly glycoproteins 713:725 arg1 lignification 815:827 lignification 815:827 lignification 815:827 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 45 gly glycoproteins 713:725 arg1 control 881:887 endoplasmic reticulum quality control 851:887 endoplasmic reticulum quality control 851:887 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 45 gly glycoproteins 713:725 arg1 trafficking 838:848 protein trafficking 830:848 protein trafficking 830:848 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 45 gly glycoproteins 713:725 arg1 transduction 801:812 signal transduction 794:812 signal transduction 794:812 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 45 gly glycoproteins 713:725 arg1 glycoproteins 713:725 the enriched glycoproteins 700:725 the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling 700:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 8 46 theme only 1056:1059 arg1 form 1076:1079 the only N-glycosylated form 1052:1079 the only N-glycosylated form 1052:1079 Interestingly, out of the two dioscorin isoforms, Dio B was the only N-glycosylated form. 36754933 8 46 theme only 1056:1059 arg1 B 1046:1046 Dio B 1042:1046 Dio B 1042:1046 Interestingly, out of the two dioscorin isoforms, Dio B was the only N-glycosylated form. 36754933 6 47 theme quality 873:879 arg1 control 881:887 endoplasmic reticulum quality control 851:887 endoplasmic reticulum quality control 851:887 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 47 theme quality 873:879 arg1 glycoproteins 713:725 the enriched glycoproteins 700:725 the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling 700:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 2 48 theme Concanavalin 305:316 arg1 chromatography 336:349 Concanavalin A lectin affinity chromatography 305:349 Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification 305:399 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 7 49 theme biochemical 937:947 arg1 validation 949:958 biochemical validation 937:958 biochemical validation of the essential glycoproteins 937:989 This was supported by biochemical validation of the essential glycoproteins. 36754933 1 50 theme important 178:186 arg1 Glycosylation 158:170 Glycosylation 158:170 Glycosylation 158:170 Glycosylation is an important post translational modification in plants. 36754933 1 50 theme important 178:186 arg1 modification 207:218 an important post translational modification 175:218 an important post translational modification in plants 175:228 Glycosylation is an important post translational modification in plants. 36754933 10 51 from presence 1276:1283 arg1 B 1266:1266 Dio B 1262:1266 Dio B 1262:1266 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 11 52 theme Dio 1396:1398 arg1 isoform 1402:1408 Dio B isoform 1396:1408 Dio B isoform 1396:1408 The analysis revealed that N-glycosylation of Dio B isoform maintains the activities associated with Dioscorin at maturity and provides an overview of protein N-glycosylation, enriching the glycoproteome database of plants especially tubers. 36754933 6 53 theme endoplasmic 851:861 arg1 reticulum 863:871 endoplasmic reticulum 851:871 endoplasmic reticulum quality control 851:887 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 1 54 theme translational 193:205 arg1 Glycosylation 158:170 Glycosylation 158:170 Glycosylation 158:170 Glycosylation is an important post translational modification in plants. 36754933 1 54 theme translational 193:205 arg1 modification 207:218 an important post translational modification 175:218 an important post translational modification in plants 175:228 Glycosylation is an important post translational modification in plants. 36754933 10 55 from Absence 1233:1239 arg1 B 1266:1266 Dio B 1262:1266 Dio B 1262:1266 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 5 56 dep peroxidases 563:573 arg1 endochitinases 576:589 peroxidases, endochitinases, calreticulin, calnexin, thaumatins and lipid transfer proteins 563:653 endochitinases 576:589 These included peroxidases, endochitinases, calreticulin, calnexin, thaumatins and lipid transfer proteins. 36754933 8 57 gly N-glycosylated 1061:1074 arg1 form 1076:1079 the only N-glycosylated form 1052:1079 the only N-glycosylated form 1052:1079 Interestingly, out of the two dioscorin isoforms, Dio B was the only N-glycosylated form. 36754933 8 57 gly N-glycosylated 1061:1074 arg1 B 1046:1046 Dio B 1042:1046 Dio B 1042:1046 Interestingly, out of the two dioscorin isoforms, Dio B was the only N-glycosylated form. 36754933 10 58 theme motif 1302:1306 arg1 presence 1276:1283 the presence 1272:1283 the presence of non-canonical motif 1272:1306 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 10 58 theme motif 1302:1306 arg1 Absence 1233:1239 Absence 1233:1239 Absence of signal peptide in Dio B 1233:1266 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 2 59 theme glycosylated 258:269 arg1 proteins 271:278 N-linked glycosylated proteins 249:278 N-linked glycosylated proteins of Dioscorea alata 249:297 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 11 60 theme isoform 1402:1408 arg1 N-glycosylation 1377:1391 N-glycosylation 1377:1391 N-glycosylation of Dio B isoform 1377:1408 The analysis revealed that N-glycosylation of Dio B isoform maintains the activities associated with Dioscorin at maturity and provides an overview of protein N-glycosylation, enriching the glycoproteome database of plants especially tubers. 36754933 11 61 theme plants 1566:1571 arg1 database 1554:1561 the glycoproteome database 1536:1561 the glycoproteome database of plants 1536:1571 The analysis revealed that N-glycosylation of Dio B isoform maintains the activities associated with Dioscorin at maturity and provides an overview of protein N-glycosylation, enriching the glycoproteome database of plants especially tubers. 36754933 10 62 from B 1266:1266 arg1 presence 1276:1283 the presence 1272:1283 the presence of non-canonical motif 1272:1306 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 10 62 from B 1266:1266 arg1 Absence 1233:1239 Absence 1233:1239 Absence of signal peptide in Dio B 1233:1266 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 2 63 theme alata 293:297 arg1 proteins 271:278 N-linked glycosylated proteins 249:278 N-linked glycosylated proteins of Dioscorea alata 249:297 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 4 64 theme sub-cellular 480:491 arg1 localization 493:504 sub-cellular localization 480:504 sub-cellular localization 480:504 Signal P and sub-cellular localization showed 42.2% of proteins to be secretory. 36754933 6 65 theme enriched 704:711 arg1 remodeling 903:912 cell wall remodeling 893:912 cell wall remodeling 893:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 65 theme enriched 704:711 arg1 lignification 815:827 lignification 815:827 lignification 815:827 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 65 theme enriched 704:711 arg1 control 881:887 endoplasmic reticulum quality control 851:887 endoplasmic reticulum quality control 851:887 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 65 theme enriched 704:711 arg1 trafficking 838:848 protein trafficking 830:848 protein trafficking 830:848 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 65 theme enriched 704:711 arg1 transduction 801:812 signal transduction 794:812 signal transduction 794:812 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 65 theme enriched 704:711 arg1 glycoproteins 713:725 the enriched glycoproteins 700:725 the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling 700:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 9 66 theme other 1137:1141 arg1 form 1143:1146 the other form 1133:1146 the other form 1133:1146 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 1 67 from modification 207:218 arg1 plants 223:228 plants 223:228 plants 223:228 Glycosylation is an important post translational modification in plants. 36754933 2 68 link N-linked 249:256 arg1 proteins 271:278 N-linked glycosylated proteins 249:278 N-linked glycosylated proteins of Dioscorea alata 249:297 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 11 69 gly N-glycosylation 1377:1391 arg1 isoform 1402:1408 Dio B isoform 1396:1408 Dio B isoform 1396:1408 The analysis revealed that N-glycosylation of Dio B isoform maintains the activities associated with Dioscorin at maturity and provides an overview of protein N-glycosylation, enriching the glycoproteome database of plants especially tubers. 36754933 6 70 theme MapMan 674:679 arg1 analysis 681:688 Gene Ontology and MapMan analysis 656:688 Gene Ontology and MapMan analysis 656:688 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 11 71 from maturity 1464:1471 arg1 Dioscorin 1451:1459 Dioscorin 1451:1459 Dioscorin at maturity 1451:1471 The analysis revealed that N-glycosylation of Dio B isoform maintains the activities associated with Dioscorin at maturity and provides an overview of protein N-glycosylation, enriching the glycoproteome database of plants especially tubers. 36754933 9 72 gly O-glycosylation 1108:1122 arg2 sites 1124:1128 O-glycosylation sites 1108:1128 O-glycosylation sites 1108:1128 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 4 73 theme proteins 522:529 arg1 proteins 522:529 proteins 522:529 proteins 522:529 Signal P and sub-cellular localization showed 42.2% of proteins to be secretory. 36754933 4 73 theme proteins 522:529 arg1 % 517:517 42.2% 513:517 42.2% of proteins 513:529 Signal P and sub-cellular localization showed 42.2% of proteins to be secretory. 36754933 11 74 theme protein 1501:1507 arg1 N-glycosylation 1509:1523 protein N-glycosylation 1501:1523 protein N-glycosylation 1501:1523 The analysis revealed that N-glycosylation of Dio B isoform maintains the activities associated with Dioscorin at maturity and provides an overview of protein N-glycosylation, enriching the glycoproteome database of plants especially tubers. 36754933 0 75 theme Glycosylated 115:126 arg1 Proteins 128:135 Glycosylated Proteins 115:135 Glycosylated Proteins 115:135 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 9 76 theme Dio 1149:1151 arg1 A 1153:1153 Dio A 1149:1153 Dio A 1149:1153 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36754933 0 77 theme Glycoproteome 9:21 arg1 Analysis 23:30 N-Linked Glycoproteome Analysis 0:30 N-Linked Glycoproteome Analysis of Diosorea alata Tuber 0:54 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 3 78 theme enriched 429:436 arg1 glycoproteins 438:450 114 enriched glycoproteins 425:450 114 enriched glycoproteins 425:450 In total, 114 enriched glycoproteins were detected. 36754933 5 79 theme transfer 637:644 arg1 peroxidases 563:573 peroxidases 563:573 peroxidases 563:573 These included peroxidases, endochitinases, calreticulin, calnexin, thaumatins and lipid transfer proteins. 36754933 5 79 theme transfer 637:644 arg1 proteins 646:653 lipid transfer proteins 631:653 lipid transfer proteins 631:653 These included peroxidases, endochitinases, calreticulin, calnexin, thaumatins and lipid transfer proteins. 36754933 0 80 theme alata 44:48 arg1 Tuber 50:54 Diosorea alata Tuber 35:54 Diosorea alata Tuber 35:54 N-Linked Glycoproteome Analysis of Diosorea alata Tuber Shows Atypical Glycosylation and Indicates Central Role of Glycosylated Proteins in Tuber Maturation. 36754933 11 81 theme N-glycosylation 1509:1523 arg1 overview 1489:1496 an overview 1486:1496 an overview of protein N-glycosylation 1486:1523 The analysis revealed that N-glycosylation of Dio B isoform maintains the activities associated with Dioscorin at maturity and provides an overview of protein N-glycosylation, enriching the glycoproteome database of plants especially tubers. 36754933 3 82 located detected 457:464 arg1 total 418:422 total 418:422 total 418:422 In total, 114 enriched glycoproteins were detected. 36754933 3 82 located detected 457:464 arg2 glycoproteins 438:450 114 enriched glycoproteins 425:450 114 enriched glycoproteins 425:450 In total, 114 enriched glycoproteins were detected. 36754933 6 83 theme protein 830:836 arg1 trafficking 838:848 protein trafficking 830:848 protein trafficking 830:848 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 83 theme protein 830:836 arg1 glycoproteins 713:725 the enriched glycoproteins 700:725 the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling 700:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 2 84 theme First 231:235 arg1 analysis 237:244 First analysis 231:244 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification 231:399 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 2 85 theme free 381:384 arg1 quantification 386:399 free quantification 381:399 free quantification 381:399 First analysis of N-linked glycosylated proteins of Dioscorea alata using Concanavalin A lectin affinity chromatography enrichment coupled with label free quantification is presented. 36754933 7 86 theme glycoproteins 977:989 arg1 validation 949:958 biochemical validation 937:958 biochemical validation of the essential glycoproteins 937:989 This was supported by biochemical validation of the essential glycoproteins. 36754933 10 87 theme atypical 1326:1333 arg1 glycosylation 1335:1347 its atypical glycosylation 1322:1347 its atypical glycosylation 1322:1347 Absence of signal peptide in Dio B and the presence of non-canonical motif hints towards its atypical glycosylation. 36754933 6 88 theme wall 898:901 arg1 glycoproteins 713:725 the enriched glycoproteins 700:725 the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling 700:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 6 88 theme wall 898:901 arg1 remodeling 903:912 cell wall remodeling 893:912 cell wall remodeling 893:912 Gene Ontology and MapMan analysis predicted the enriched glycoproteins to be involved in processes essential for tuber maturation namely: signal transduction, lignification, protein trafficking, endoplasmic reticulum quality control and cell wall remodeling. 36754933 8 89 theme dioscorin 1022:1030 arg1 isoforms 1032:1039 the two dioscorin isoforms 1014:1039 the two dioscorin isoforms 1014:1039 Interestingly, out of the two dioscorin isoforms, Dio B was the only N-glycosylated form. 36754933 9 90 theme sweet 1219:1223 arg1 potato 1225:1230 sweet potato 1219:1230 sweet potato 1219:1230 In silico analysis showed O-glycosylation sites in the other form, Dio A suggesting its similarity with sporamin, the storage protein of sweet potato. 36285915 5 0 theme host-microbe 722:733 arg1 interactions 735:746 host-microbe interactions 722:746 host-microbe interactions 722:746 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 7 1 theme intestinal 1199:1208 arg1 homeostasis 1210:1220 intestinal homeostasis 1199:1220 intestinal homeostasis 1199:1220 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 6 2 from GTRs 1011:1014 arg1 identification 929:942 the identification 925:942 the identification of peptide sequences 925:963 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 6 2 from GTRs 1011:1014 arg1 composition 973:983 the composition 969:983 the composition of glycan moieties in the GTRs 969:1014 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 7 3 theme GT 1029:1030 arg1 fractions 1040:1048 GT peptide fractions 1029:1048 GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, 1029:1134 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 1 4 theme protein 158:164 arg1 peptides 139:146 Bioactive peptides 129:146 Bioactive peptides (BPs) 129:152 Bioactive peptides (BPs) are protein fragments that benefit human health. 36285915 1 4 theme protein 158:164 arg1 fragments 166:174 protein fragments 158:174 protein fragments that benefit human health 158:200 Bioactive peptides (BPs) are protein fragments that benefit human health. 36285915 7 5 theme peptide 1032:1038 arg1 fractions 1040:1048 GT peptide fractions 1029:1048 GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, 1029:1134 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 5 6 theme interactions 735:746 arg1 mediators 709:717 potential mediators 699:717 potential mediators of host-microbe interactions 699:746 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 6 7 theme thin-layer 891:900 arg1 chromatography 902:915 thin-layer chromatography 891:915 thin-layer chromatography 891:915 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 3 8 theme protein 464:470 arg1 analyses 472:479 conserved protein analyses 454:479 conserved protein analyses 454:479 Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. 36285915 7 9 attach isolated 1118:1125 arg2 strain 1111:1116 a strain 1109:1116 a strain isolated from GT 1109:1133 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 7 9 attach isolated 1118:1125 arg2 331261 1101:1106 Lactiplantibacillus plantarum APsulloc 331261 1062:1106 Lactiplantibacillus plantarum APsulloc 331261 1062:1106 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 7 9 attach isolated 1118:1125 arg1 GT 1132:1133 GT 1132:1133 GT 1132:1133 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 6 10 theme moieties 995:1002 arg1 identification 929:942 the identification 925:942 the identification of peptide sequences 925:963 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 6 10 theme moieties 995:1002 arg1 composition 973:983 the composition 969:983 the composition of glycan moieties in the GTRs 969:1014 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 0 11 theme anaerobic 108:116 arg1 digestion 118:126 probiotics-aided anaerobic digestion 91:126 probiotics-aided anaerobic digestion 91:126 Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion. 36285915 2 12 from embedded 393:400 arg1 GTRs 405:408 GTRs 405:408 GTRs 405:408 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 3 13 theme GTR 530:532 arg1 hydrolysis 534:543 GTR hydrolysis 530:543 GTR hydrolysis 530:543 Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. 36285915 8 14 theme biological 1340:1349 arg1 process 1351:1357 a biological process 1338:1357 a biological process for recycling GTRs from agro-waste 1338:1392 Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs. 36285915 3 15 theme probiotic 508:516 arg1 strains 518:524 a few probiotic strains 502:524 a few probiotic strains for GTR hydrolysis 502:543 Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. 36285915 6 16 theme glycan 988:993 arg1 moieties 995:1002 glycan moieties 988:1002 glycan moieties in the GTRs 988:1014 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 0 17 theme probiotics-aided 91:106 arg1 digestion 118:126 probiotics-aided anaerobic digestion 91:126 probiotics-aided anaerobic digestion 91:126 Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion. 36285915 3 18 theme conserved 454:462 arg1 analyses 472:479 conserved protein analyses 454:479 conserved protein analyses 454:479 Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. 36285915 2 19 from GTRs 405:408 arg1 embedded 393:400 embedded 393:400 embedded 393:400 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 8 20 theme probiotics-aided 1275:1290 arg1 hydrolysates 1296:1307 probiotics-aided GTR hydrolysates 1275:1307 probiotics-aided GTR hydrolysates 1275:1307 Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs. 36285915 1 21 theme human 189:193 arg1 health 195:200 human health 189:200 human health 189:200 Bioactive peptides (BPs) are protein fragments that benefit human health. 36285915 5 22 theme protein-coupled 830:844 arg1 receptors 846:854 168 human G protein-coupled receptors 818:854 168 human G protein-coupled receptors (GPCRs) 818:862 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 5 22 theme protein-coupled 830:844 arg1 GPCRs 857:861 GPCRs 857:861 GPCRs 857:861 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 5 23 theme potential 699:707 arg1 mediators 709:717 potential mediators 699:717 potential mediators of host-microbe interactions 699:746 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 4 24 theme peptide 619:625 arg1 fractions 627:635 GTR-derived peptide fractions 607:635 GTR-derived peptide fractions 607:635 The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. 36285915 5 25 theme agonistic 777:785 arg1 activities 804:813 agonistic and antagonistic activities 777:813 agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs) 777:862 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 7 26 theme APsulloc 1092:1099 arg1 331261 1101:1106 Lactiplantibacillus plantarum APsulloc 331261 1062:1106 Lactiplantibacillus plantarum APsulloc 331261 1062:1106 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 7 26 theme APsulloc 1092:1099 arg1 strain 1111:1116 a strain 1109:1116 a strain isolated from GT 1109:1133 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 6 27 theme NanoLC-MS/MS 865:876 arg1 analysis 878:885 NanoLC-MS/MS analysis 865:885 NanoLC-MS/MS analysis 865:885 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 2 28 theme BIOPEP 346:351 arg1 database 353:360 the BIOPEP database 342:360 the BIOPEP database 342:360 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 2 29 theme embedded 393:400 arg1 BPs 389:391 BPs 389:391 BPs embedded in GTRs 389:408 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 7 30 theme potent-binding 1145:1158 arg1 activity 1160:1167 a potent-binding activity 1143:1167 a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis 1143:1220 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 0 31 theme green 25:29 arg1 residues 35:42 leftover green tea residues 16:42 leftover green tea residues 16:42 Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion. 36285915 8 32 theme recycling 1363:1371 arg1 GTRs 1373:1376 recycling GTRs 1363:1376 recycling GTRs from agro-waste 1363:1392 Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs. 36285915 2 33 theme BPs 389:391 arg1 range 380:384 a wide range 373:384 a wide range of BPs embedded in GTRs 373:408 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 7 34 theme Lactiplantibacillus 1062:1080 arg1 331261 1101:1106 Lactiplantibacillus plantarum APsulloc 331261 1062:1106 Lactiplantibacillus plantarum APsulloc 331261 1062:1106 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 7 34 theme Lactiplantibacillus 1062:1080 arg1 strain 1111:1116 a strain 1109:1116 a strain isolated from GT 1109:1133 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 2 35 theme new 284:286 arg1 BPs 288:290 new BPs 284:290 new BPs 284:290 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 3 36 theme Comparative 411:421 arg1 genomics 423:430 Comparative genomics 411:430 Comparative genomics 411:430 Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. 36285915 0 37 theme leftover 16:23 arg1 residues 35:42 leftover green tea residues 16:42 leftover green tea residues 16:42 Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion. 36285915 7 38 theme plantarum 1082:1090 arg1 331261 1101:1106 Lactiplantibacillus plantarum APsulloc 331261 1062:1106 Lactiplantibacillus plantarum APsulloc 331261 1062:1106 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 7 38 theme plantarum 1082:1090 arg1 strain 1111:1116 a strain 1109:1116 a strain isolated from GT 1109:1133 Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. 36285915 2 39 dep in 306:307 arg1 silico 309:314 silico 309:314 silico 309:314 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 2 40 theme wide 375:378 arg1 range 380:384 a wide range 373:384 a wide range of BPs embedded in GTRs 373:408 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 0 41 theme residues 35:42 arg1 Valorization 0:11 Valorization 0:11 Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion. 0:127 Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion. 36285915 6 42 theme sequences 955:963 arg1 identification 929:942 the identification 925:942 the identification of peptide sequences 925:963 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 6 42 theme sequences 955:963 arg1 composition 973:983 the composition 969:983 the composition of glycan moieties in the GTRs 969:1014 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 6 43 from composition 973:983 arg1 GTRs 1011:1014 the GTRs 1007:1014 the GTRs 1007:1014 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 5 44 theme human 822:826 arg1 receptors 846:854 168 human G protein-coupled receptors 818:854 168 human G protein-coupled receptors (GPCRs) 818:862 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 5 44 theme human 822:826 arg1 GPCRs 857:861 GPCRs 857:861 GPCRs 857:861 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 8 45 theme renewable 1399:1407 arg1 resources 1409:1417 renewable resources 1399:1417 renewable resources as health-promoting BPs 1399:1441 Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs. 36285915 4 46 theme GTR-derived 607:617 arg1 fractions 627:635 GTR-derived peptide fractions 607:635 GTR-derived peptide fractions 607:635 The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. 36285915 0 47 theme tea 31:33 arg1 residues 35:42 leftover green tea residues 16:42 leftover green tea residues 16:42 Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion. 36285915 6 48 theme peptide 947:953 arg1 sequences 955:963 peptide sequences 947:963 peptide sequences 947:963 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 5 49 theme peptide 672:678 arg1 fractions 680:688 green tea (GT) peptide fractions 657:688 green tea (GT) peptide fractions 657:688 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 8 50 theme postbiotic 1312:1321 arg1 BPs 1323:1325 postbiotic BPs 1312:1325 postbiotic BPs 1312:1325 Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs. 36285915 2 51 theme tea 236:238 arg1 GTRs 250:253 GTRs 250:253 GTRs 250:253 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 2 51 theme tea 236:238 arg1 resource 271:278 a resource 269:278 a resource for new BPs 269:290 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 2 51 theme tea 236:238 arg1 residues 240:247 leftover green tea residues 221:247 leftover green tea residues (GTRs) 221:254 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 5 52 theme antagonistic 791:802 arg1 activities 804:813 agonistic and antagonistic activities 777:813 agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs) 777:862 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 8 53 theme GTR 1292:1294 arg1 hydrolysates 1296:1307 probiotics-aided GTR hydrolysates 1275:1307 probiotics-aided GTR hydrolysates 1275:1307 Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs. 36285915 6 54 from identification 929:942 arg1 GTRs 1011:1014 the GTRs 1007:1014 the GTRs 1007:1014 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 2 55 theme green 230:234 arg1 tea 236:238 leftover green tea 221:238 leftover green tea residues (GTRs) 221:254 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 1 56 theme Bioactive 129:137 arg1 BPs 149:151 BPs 149:151 BPs 149:151 Bioactive peptides (BPs) are protein fragments that benefit human health. 36285915 1 56 theme Bioactive 129:137 arg1 peptides 139:146 Bioactive peptides 129:146 Bioactive peptides (BPs) 129:152 Bioactive peptides (BPs) are protein fragments that benefit human health. 36285915 1 56 theme Bioactive 129:137 arg1 fragments 166:174 protein fragments 158:174 protein fragments that benefit human health 158:200 Bioactive peptides (BPs) are protein fragments that benefit human health. 36285915 6 57 from moieties 995:1002 arg1 GTRs 1011:1014 the GTRs 1007:1014 the GTRs 1007:1014 NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. 36285915 2 58 theme leftover 221:228 arg1 tea 236:238 leftover green tea 221:238 leftover green tea residues (GTRs) 221:254 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 2 59 theme in 306:307 arg1 proteolysis 316:326 in silico proteolysis 306:326 in silico proteolysis of GTRs 306:334 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 5 60 theme green 657:661 arg1 GT 668:669 GT 668:669 GT 668:669 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 5 60 theme green 657:661 arg1 tea 663:665 green tea 657:665 green tea (GT) peptide fractions 657:688 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 4 61 link GTR-derived 607:617 arg1 fractions 627:635 GTR-derived peptide fractions 607:635 GTR-derived peptide fractions 607:635 The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. 36285915 3 62 theme few 504:506 arg1 strains 518:524 a few probiotic strains 502:524 a few probiotic strains for GTR hydrolysis 502:543 Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. 36285915 5 63 theme tea 663:665 arg1 fractions 680:688 green tea (GT) peptide fractions 657:688 green tea (GT) peptide fractions 657:688 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 8 64 theme health-promoting 1422:1437 arg1 BPs 1439:1441 health-promoting BPs 1422:1441 health-promoting BPs 1422:1441 Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs. 36285915 8 65 theme hydrolysates 1296:1307 arg1 use 1268:1270 the potential use 1254:1270 the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs 1254:1325 Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs. 36285915 4 66 theme selected 550:557 arg1 probiotics 559:568 The selected probiotics 546:568 The selected probiotics 546:568 The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. 36285915 0 67 theme bioactive 66:74 arg1 peptides 76:83 bioactive peptides 66:83 bioactive peptides using probiotics-aided anaerobic digestion 66:126 Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion. 36285915 8 68 theme potential 1258:1266 arg1 use 1268:1270 the potential use 1254:1270 the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs 1254:1325 Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs. 36285915 3 69 theme analyses 472:479 arg1 percentage 440:449 the percentage 436:449 the percentage of conserved protein analyses 436:479 Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. 36285915 3 69 theme analyses 472:479 arg1 genomics 423:430 Comparative genomics 411:430 Comparative genomics 411:430 Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. 36285915 5 70 theme receptors 846:854 arg1 activities 804:813 agonistic and antagonistic activities 777:813 agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs) 777:862 To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). 36285915 4 71 theme GTRs 579:582 arg1 anaerobically 584:596 GTRs anaerobically 579:596 GTRs anaerobically 579:596 The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. 36285915 2 72 theme GTRs 331:334 arg1 proteolysis 316:326 in silico proteolysis 306:326 in silico proteolysis of GTRs 306:334 To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. 36285915 8 73 from agro-waste 1383:1392 arg1 GTRs 1373:1376 recycling GTRs 1363:1376 recycling GTRs from agro-waste 1363:1392 Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs. 36309312 8 0 gly glycosylation 1280:1292 arg2 sites 1294:1298 individual glycosylation sites 1269:1298 individual glycosylation sites 1269:1298 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 9 1 from differences 1377:1387 arg1 compartments 1404:1415 subcellular compartments 1392:1415 subcellular compartments 1392:1415 Further analysis revealed glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans. 36309312 9 1 from differences 1377:1387 arg1 glycoproteins 1449:1461 glycoproteins 1449:1461 glycoproteins in the lysosome frequently modified with paucimannosidic glycans 1449:1526 Further analysis revealed glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans. 36309312 2 2 theme particular 331:340 arg1 analysis 386:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 9 3 from glycoproteins 1449:1461 arg1 lysosome 1470:1477 the lysosome 1466:1477 the lysosome frequently modified with paucimannosidic glycans 1466:1526 Further analysis revealed glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans. 36309312 3 4 theme interaction 520:530 arg1 chromatography 532:545 hydrophilic interaction chromatography 508:545 hydrophilic interaction chromatography 508:545 To elucidate the N-glycoproteome landscape, we developed an approach based on multi-lectin affinity enrichment, hydrophilic interaction chromatography, and LC-MS-based glycoproteomics. 36309312 10 5 theme clinical 1612:1619 arg1 severity 1636:1643 AD clinical and pathologic severity 1609:1643 AD clinical and pathologic severity 1609:1643 These results illustrate the N-glycoproteomics landscape across the spectrum of AD clinical and pathologic severity and will facilitate a deeper understanding of progression and treatment development. 36309312 8 6 theme fucosylation 1215:1226 arg1 number 1182:1187 the number 1178:1187 the number of antennae 1178:1199 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 6 theme fucosylation 1215:1226 arg1 bisection 1229:1237 bisection 1229:1237 bisection 1229:1237 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 6 theme fucosylation 1215:1226 arg1 monosaccharides 1250:1264 other monosaccharides 1244:1264 other monosaccharides at individual glycosylation sites 1244:1298 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 6 theme fucosylation 1215:1226 arg1 frequency 1202:1210 frequency 1202:1210 frequency of fucosylation 1202:1226 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 4 7 gly glycoproteins 730:742 arg1 glycoproteins 730:742 over 300 glycoproteins 721:742 over 300 glycoproteins 721:742 We analyzed brain tissue from 10 persons with no cognitive impairment or AD, 10 with asymptomatic AD, and 10 with symptomatic AD, detecting over 300 glycoproteins and 1900 glycoforms across the samples. 36309312 10 8 dep progression 1691:1701 arg1 development 1717:1727 development 1717:1727 development 1717:1727 These results illustrate the N-glycoproteomics landscape across the spectrum of AD clinical and pathologic severity and will facilitate a deeper understanding of progression and treatment development. 36309312 8 9 from sites 1294:1298 arg1 number 1182:1187 the number 1178:1187 the number of antennae 1178:1199 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 9 from sites 1294:1298 arg1 bisection 1229:1237 bisection 1229:1237 bisection 1229:1237 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 9 from sites 1294:1298 arg1 monosaccharides 1250:1264 other monosaccharides 1244:1264 other monosaccharides at individual glycosylation sites 1244:1298 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 9 from sites 1294:1298 arg1 frequency 1202:1210 frequency 1202:1210 frequency of fucosylation 1202:1226 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 9 from sites 1294:1298 arg1 differences 1163:1173 AD-associated differences 1149:1173 AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups 1149:1334 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 10 10 theme severity 1636:1643 arg1 spectrum 1597:1604 the spectrum 1593:1604 the spectrum of AD clinical and pathologic severity 1593:1643 These results illustrate the N-glycoproteomics landscape across the spectrum of AD clinical and pathologic severity and will facilitate a deeper understanding of progression and treatment development. 36309312 6 11 theme glycoforms 981:990 arg1 % 966:966 >20% 963:966 >20% of the total glycoforms 963:990 The Man5 N-glycan was found to occur most frequently at >20% of the total glycoforms. 36309312 6 11 theme glycoforms 981:990 arg1 glycoforms 981:990 the total glycoforms 971:990 the total glycoforms 971:990 The Man5 N-glycan was found to occur most frequently at >20% of the total glycoforms. 36309312 2 12 theme AD 298:299 arg1 progression 301:311 AD progression 298:311 AD progression 298:311 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 6 13 theme Man5 911:914 arg1 N-glycan 916:923 The Man5 N-glycan 907:923 The Man5 N-glycan 907:923 The Man5 N-glycan was found to occur most frequently at >20% of the total glycoforms. 36309312 5 14 gly fucosylated 881:891 arg1 N-glycans 819:827 N-glycans 819:827 N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected 819:904 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 5 14 gly fucosylated 881:891 arg1 chains 865:870 high-mannosidic or complex chains 838:870 high-mannosidic or complex chains that are fucosylated and bisected 838:904 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 2 15 theme abundance 249:257 arg1 role 233:236 the role 229:236 the role of protein abundance and posttranslational modifications in AD progression and treatment 229:325 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 9 16 theme glycosylation 1363:1375 arg1 differences 1377:1387 glycosylation differences 1363:1387 glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans 1363:1526 Further analysis revealed glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans. 36309312 6 17 theme total 975:979 arg1 glycoforms 981:990 the total glycoforms 971:990 the total glycoforms 971:990 The Man5 N-glycan was found to occur most frequently at >20% of the total glycoforms. 36309312 4 18 theme symptomatic 695:705 arg1 AD 707:708 symptomatic AD 695:708 symptomatic AD 695:708 We analyzed brain tissue from 10 persons with no cognitive impairment or AD, 10 with asymptomatic AD, and 10 with symptomatic AD, detecting over 300 glycoproteins and 1900 glycoforms across the samples. 36309312 7 19 theme N-glycoproteome 1081:1095 arg1 sialylation 1037:1047 sialylation 1037:1047 sialylation 1037:1047 Unlike the glycoproteomes of other tissues, sialylation is a minor feature of the brain N-glycoproteome, occurring at <9% among the glycoforms. 36309312 7 19 theme N-glycoproteome 1081:1095 arg1 feature 1060:1066 a minor feature 1052:1066 a minor feature 1052:1066 Unlike the glycoproteomes of other tissues, sialylation is a minor feature of the brain N-glycoproteome, occurring at <9% among the glycoforms. 36309312 2 20 theme protein 241:247 arg1 abundance 249:257 protein abundance 241:257 protein abundance 241:257 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 10 21 theme treatment 1707:1715 arg1 understanding 1674:1686 a deeper understanding 1665:1686 a deeper understanding of progression and treatment development 1665:1727 These results illustrate the N-glycoproteomics landscape across the spectrum of AD clinical and pathologic severity and will facilitate a deeper understanding of progression and treatment development. 36309312 5 22 theme glycoproteins 800:812 arg1 majority 788:795 The majority 784:795 The majority of glycoproteins 784:812 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 10 23 theme progression 1691:1701 arg1 understanding 1674:1686 a deeper understanding 1665:1686 a deeper understanding of progression and treatment development 1665:1727 These results illustrate the N-glycoproteomics landscape across the spectrum of AD clinical and pathologic severity and will facilitate a deeper understanding of progression and treatment development. 36309312 3 24 theme LC-MS-based 552:562 arg1 glycoproteomics 564:578 LC-MS-based glycoproteomics 552:578 LC-MS-based glycoproteomics 552:578 To elucidate the N-glycoproteome landscape, we developed an approach based on multi-lectin affinity enrichment, hydrophilic interaction chromatography, and LC-MS-based glycoproteomics. 36309312 4 25 theme asymptomatic 666:677 arg1 AD 679:680 asymptomatic AD 666:680 asymptomatic AD 666:680 We analyzed brain tissue from 10 persons with no cognitive impairment or AD, 10 with asymptomatic AD, and 10 with symptomatic AD, detecting over 300 glycoproteins and 1900 glycoforms across the samples. 36309312 10 26 theme pathologic 1625:1634 arg1 severity 1636:1643 AD clinical and pathologic severity 1609:1643 AD clinical and pathologic severity 1609:1643 These results illustrate the N-glycoproteomics landscape across the spectrum of AD clinical and pathologic severity and will facilitate a deeper understanding of progression and treatment development. 36309312 1 27 theme Molecular 91:99 arg1 changes 101:107 Molecular changes 91:107 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) 91:175 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) are an intense area of study. 36309312 1 27 theme Molecular 91:99 arg1 area 192:195 an intense area 181:195 an intense area of study 181:204 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) are an intense area of study. 36309312 2 28 theme glycoproteomics 370:384 arg1 analysis 386:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 0 29 theme Glycoproteomics 0:14 arg1 Landscape 16:24 Glycoproteomics Landscape 0:24 Glycoproteomics Landscape of Asymptomatic and Symptomatic Human Alzheimer's Disease 0:82 Glycoproteomics Landscape of Asymptomatic and Symptomatic Human Alzheimer's Disease Brain. 36309312 10 30 theme deeper 1667:1672 arg1 understanding 1674:1686 a deeper understanding 1665:1686 a deeper understanding of progression and treatment development 1665:1727 These results illustrate the N-glycoproteomics landscape across the spectrum of AD clinical and pathologic severity and will facilitate a deeper understanding of progression and treatment development. 36309312 7 31 theme brain 1075:1079 arg1 N-glycoproteome 1081:1095 the brain N-glycoproteome 1071:1095 the brain N-glycoproteome 1071:1095 Unlike the glycoproteomes of other tissues, sialylation is a minor feature of the brain N-glycoproteome, occurring at <9% among the glycoforms. 36309312 0 32 dep Brain 84:88 arg1 Landscape 16:24 Glycoproteomics Landscape 0:24 Glycoproteomics Landscape of Asymptomatic and Symptomatic Human Alzheimer's Disease 0:82 Glycoproteomics Landscape of Asymptomatic and Symptomatic Human Alzheimer's Disease Brain. 36309312 2 33 theme N-linked 361:368 arg1 analysis 386:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 0 34 theme Asymptomatic 29:40 arg1 Disease 76:82 Asymptomatic and Symptomatic Human Alzheimer's Disease 29:82 Asymptomatic and Symptomatic Human Alzheimer's Disease 29:82 Glycoproteomics Landscape of Asymptomatic and Symptomatic Human Alzheimer's Disease Brain. 36309312 9 35 gly glycoproteins 1449:1461 arg1 glycoproteins 1449:1461 glycoproteins 1449:1461 glycoproteins in the lysosome frequently modified with paucimannosidic glycans 1449:1526 Further analysis revealed glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans. 36309312 2 36 theme modifications 281:293 arg1 role 233:236 the role 229:236 the role of protein abundance and posttranslational modifications in AD progression and treatment 229:325 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 5 37 theme high-mannosidic 838:852 arg1 N-glycans 819:827 N-glycans 819:827 N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected 819:904 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 5 37 theme high-mannosidic 838:852 arg1 chains 865:870 high-mannosidic or complex chains 838:870 high-mannosidic or complex chains that are fucosylated and bisected 838:904 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 9 38 theme Further 1337:1343 arg1 analysis 1345:1352 Further analysis 1337:1352 Further analysis 1337:1352 Further analysis revealed glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans. 36309312 4 39 theme cognitive 630:638 arg1 impairment 640:649 no cognitive impairment 627:649 no cognitive impairment 627:649 We analyzed brain tissue from 10 persons with no cognitive impairment or AD, 10 with asymptomatic AD, and 10 with symptomatic AD, detecting over 300 glycoproteins and 1900 glycoforms across the samples. 36309312 2 40 theme posttranslational 263:279 arg1 modifications 281:293 posttranslational modifications 263:293 posttranslational modifications 263:293 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 2 41 from role 233:236 arg1 treatment 317:325 treatment 317:325 treatment 317:325 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 2 41 from role 233:236 arg1 progression 301:311 AD progression 298:311 AD progression 298:311 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 1 42 theme intense 184:190 arg1 changes 101:107 Molecular changes 91:107 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) 91:175 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) are an intense area of study. 36309312 1 42 theme intense 184:190 arg1 area 192:195 an intense area 181:195 an intense area of study 181:204 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) are an intense area of study. 36309312 0 43 theme Symptomatic 46:56 arg1 Disease 76:82 Asymptomatic and Symptomatic Human Alzheimer's Disease 29:82 Asymptomatic and Symptomatic Human Alzheimer's Disease 29:82 Glycoproteomics Landscape of Asymptomatic and Symptomatic Human Alzheimer's Disease Brain. 36309312 4 44 theme brain 593:597 arg1 tissue 599:604 brain tissue 593:604 brain tissue from 10 persons with no cognitive impairment or AD, 10 with asymptomatic AD, and 10 with symptomatic AD 593:708 We analyzed brain tissue from 10 persons with no cognitive impairment or AD, 10 with asymptomatic AD, and 10 with symptomatic AD, detecting over 300 glycoproteins and 1900 glycoforms across the samples. 36309312 2 45 link N-linked 361:368 arg1 analysis 386:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 8 46 from groups 1329:1334 arg1 samples 1306:1312 samples 1306:1312 samples from our three groups 1306:1334 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 5 47 theme complex 857:863 arg1 N-glycans 819:827 N-glycans 819:827 N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected 819:904 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 5 47 theme complex 857:863 arg1 chains 865:870 high-mannosidic or complex chains 838:870 high-mannosidic or complex chains that are fucosylated and bisected 838:904 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 3 48 theme N-glycoproteome 413:427 arg1 landscape 429:437 the N-glycoproteome landscape 409:437 the N-glycoproteome landscape 409:437 To elucidate the N-glycoproteome landscape, we developed an approach based on multi-lectin affinity enrichment, hydrophilic interaction chromatography, and LC-MS-based glycoproteomics. 36309312 7 49 theme minor 1054:1058 arg1 sialylation 1037:1047 sialylation 1037:1047 sialylation 1037:1047 Unlike the glycoproteomes of other tissues, sialylation is a minor feature of the brain N-glycoproteome, occurring at <9% among the glycoforms. 36309312 7 49 theme minor 1054:1058 arg1 feature 1060:1066 a minor feature 1052:1066 a minor feature 1052:1066 Unlike the glycoproteomes of other tissues, sialylation is a minor feature of the brain N-glycoproteome, occurring at <9% among the glycoforms. 36309312 8 50 theme AD-associated 1149:1161 arg1 differences 1163:1173 AD-associated differences 1149:1173 AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups 1149:1334 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 10 51 theme N-glycoproteomics 1558:1574 arg1 landscape 1576:1584 the N-glycoproteomics landscape 1554:1584 the N-glycoproteomics landscape across the spectrum of AD clinical and pathologic severity 1554:1643 These results illustrate the N-glycoproteomics landscape across the spectrum of AD clinical and pathologic severity and will facilitate a deeper understanding of progression and treatment development. 36309312 3 52 theme hydrophilic 508:518 arg1 chromatography 532:545 hydrophilic interaction chromatography 508:545 hydrophilic interaction chromatography 508:545 To elucidate the N-glycoproteome landscape, we developed an approach based on multi-lectin affinity enrichment, hydrophilic interaction chromatography, and LC-MS-based glycoproteomics. 36309312 8 53 theme antennae 1192:1199 arg1 number 1182:1187 the number 1178:1187 the number of antennae 1178:1199 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 53 theme antennae 1192:1199 arg1 bisection 1229:1237 bisection 1229:1237 bisection 1229:1237 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 53 theme antennae 1192:1199 arg1 monosaccharides 1250:1264 other monosaccharides 1244:1264 other monosaccharides at individual glycosylation sites 1244:1298 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 53 theme antennae 1192:1199 arg1 frequency 1202:1210 frequency 1202:1210 frequency of fucosylation 1202:1226 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 5 54 contain have 814:817 arg2 N-glycans 819:827 N-glycans 819:827 N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected 819:904 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 5 54 contain have 814:817 arg2 chains 865:870 high-mannosidic or complex chains 838:870 high-mannosidic or complex chains that are fucosylated and bisected 838:904 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 5 54 contain have 814:817 arg1 majority 788:795 The majority 784:795 The majority of glycoproteins 784:812 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 9 55 theme paucimannosidic 1504:1518 arg1 glycans 1520:1526 paucimannosidic glycans 1504:1526 paucimannosidic glycans 1504:1526 Further analysis revealed glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans. 36309312 7 56 theme other 1022:1026 arg1 tissues 1028:1034 other tissues 1022:1034 other tissues 1022:1034 Unlike the glycoproteomes of other tissues, sialylation is a minor feature of the brain N-glycoproteome, occurring at <9% among the glycoforms. 36309312 8 57 theme glycosylation 1280:1292 arg1 sites 1294:1298 individual glycosylation sites 1269:1298 individual glycosylation sites 1269:1298 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 0 58 theme Human 58:62 arg1 Disease 76:82 Asymptomatic and Symptomatic Human Alzheimer's Disease 29:82 Asymptomatic and Symptomatic Human Alzheimer's Disease 29:82 Glycoproteomics Landscape of Asymptomatic and Symptomatic Human Alzheimer's Disease Brain. 36309312 8 59 from differences 1163:1173 arg1 number 1182:1187 the number 1178:1187 the number of antennae 1178:1199 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 59 from differences 1163:1173 arg1 sites 1294:1298 individual glycosylation sites 1269:1298 individual glycosylation sites 1269:1298 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 59 from differences 1163:1173 arg1 monosaccharides 1250:1264 other monosaccharides 1244:1264 other monosaccharides at individual glycosylation sites 1244:1298 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 59 from differences 1163:1173 arg1 frequency 1202:1210 frequency 1202:1210 frequency of fucosylation 1202:1226 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 59 from differences 1163:1173 arg1 bisection 1229:1237 bisection 1229:1237 bisection 1229:1237 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 8 60 theme individual 1269:1278 arg1 sites 1294:1298 individual glycosylation sites 1269:1298 individual glycosylation sites 1269:1298 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 7 61 theme tissues 1028:1034 arg1 glycoproteomes 1004:1017 the glycoproteomes 1000:1017 the glycoproteomes of other tissues 1000:1034 Unlike the glycoproteomes of other tissues, sialylation is a minor feature of the brain N-glycoproteome, occurring at <9% among the glycoforms. 36309312 1 62 theme individuals 125:135 arg1 brain 116:120 the brain 112:120 the brain of individuals afflicted with Alzheimer's disease (AD) 112:175 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) are an intense area of study. 36309312 9 63 theme subcellular 1392:1402 arg1 compartments 1404:1415 subcellular compartments 1392:1415 subcellular compartments 1392:1415 Further analysis revealed glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans. 36309312 9 63 theme subcellular 1392:1402 arg1 glycoproteins 1449:1461 glycoproteins 1449:1461 glycoproteins in the lysosome frequently modified with paucimannosidic glycans 1449:1526 Further analysis revealed glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans. 36309312 1 64 theme study 200:204 arg1 changes 101:107 Molecular changes 91:107 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) 91:175 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) are an intense area of study. 36309312 1 64 theme study 200:204 arg1 area 192:195 an intense area 181:195 an intense area of study 181:204 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) are an intense area of study. 36309312 4 65 with persons 614:620 arg1 AD 654:655 AD 654:655 AD 654:655 We analyzed brain tissue from 10 persons with no cognitive impairment or AD, 10 with asymptomatic AD, and 10 with symptomatic AD, detecting over 300 glycoproteins and 1900 glycoforms across the samples. 36309312 4 65 with persons 614:620 arg1 impairment 640:649 no cognitive impairment 627:649 no cognitive impairment 627:649 We analyzed brain tissue from 10 persons with no cognitive impairment or AD, 10 with asymptomatic AD, and 10 with symptomatic AD, detecting over 300 glycoproteins and 1900 glycoforms across the samples. 36309312 3 66 theme affinity 487:494 arg1 enrichment 496:505 multi-lectin affinity enrichment 474:505 multi-lectin affinity enrichment 474:505 To elucidate the N-glycoproteome landscape, we developed an approach based on multi-lectin affinity enrichment, hydrophilic interaction chromatography, and LC-MS-based glycoproteomics. 36309312 3 67 theme multi-lectin 474:485 arg1 enrichment 496:505 multi-lectin affinity enrichment 474:505 multi-lectin affinity enrichment 474:505 To elucidate the N-glycoproteome landscape, we developed an approach based on multi-lectin affinity enrichment, hydrophilic interaction chromatography, and LC-MS-based glycoproteomics. 36309312 5 68 gly glycoproteins 800:812 arg1 glycoproteins 800:812 glycoproteins 800:812 glycoproteins 800:812 The majority of glycoproteins have N-glycans that are high-mannosidic or complex chains that are fucosylated and bisected. 36309312 8 69 theme other 1244:1248 arg1 monosaccharides 1250:1264 other monosaccharides 1244:1264 other monosaccharides at individual glycosylation sites 1244:1298 We observed AD-associated differences in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among samples from our three groups. 36309312 2 70 theme intact 354:359 arg1 analysis 386:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 1 71 from changes 101:107 arg1 brain 116:120 the brain 112:120 the brain of individuals afflicted with Alzheimer's disease (AD) 112:175 Molecular changes in the brain of individuals afflicted with Alzheimer's disease (AD) are an intense area of study. 36309312 9 72 theme disease 1424:1430 arg1 stage 1432:1436 disease stage 1424:1436 disease stage 1424:1436 Further analysis revealed glycosylation differences in subcellular compartments across disease stage, including glycoproteins in the lysosome frequently modified with paucimannosidic glycans. 36309312 2 73 theme large-scale 342:352 arg1 analysis 386:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 particular large-scale intact N-linked glycoproteomics analysis 331:393 Little is known about the role of protein abundance and posttranslational modifications in AD progression and treatment, in particular large-scale intact N-linked glycoproteomics analysis. 36309312 4 74 from persons 614:620 arg1 tissue 599:604 brain tissue 593:604 brain tissue from 10 persons with no cognitive impairment or AD, 10 with asymptomatic AD, and 10 with symptomatic AD 593:708 We analyzed brain tissue from 10 persons with no cognitive impairment or AD, 10 with asymptomatic AD, and 10 with symptomatic AD, detecting over 300 glycoproteins and 1900 glycoforms across the samples. 35371997 10 0 theme increased 1595:1603 arg1 burden 1614:1619 an increased leukemia burden 1592:1619 an increased leukemia burden 1592:1619 Upon vincristine discontinuation, relapse was detected in both groups, but mice transplanted with ST6Gal1 overexpressing BCP-ALL cells had an increased leukemia burden and shorter survival than controls. 35371997 12 1 theme Gene 1824:1827 arg1 analysis 1840:1847 Gene expression analysis 1824:1847 Gene expression analysis using RNA-seq 1824:1861 Gene expression analysis using RNA-seq showed a surprisingly large number of genes with significantly differential expression, of which approximately 60% increased mRNAs, in the ST6Gal1 overexpressing BCP-ALL cells. 35371997 13 2 theme immune 2104:2109 arg1 migration 2116:2124 immune cell migration 2104:2124 immune cell migration 2104:2124 Pathways significantly downregulated included those involved in immune cell migration. 35371997 1 3 theme Normal 97:102 arg1 development 123:133 Normal early human B-cell development 97:133 Normal early human B-cell development from lymphoid progenitors in the bone marrow 97:178 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 3 4 theme sialic 562:567 arg1 acids 569:573 sialic acids 562:573 sialic acids in an α2-6-linkage 562:592 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 15 5 theme glycoprotein 2398:2409 arg1 substrates 2411:2420 many N-linked glycoprotein substrates 2384:2420 many N-linked glycoprotein substrates 2384:2420 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 8 6 theme original 1222:1229 arg1 levels 1239:1244 original ST6Gal1 levels 1222:1244 original ST6Gal1 levels 1222:1244 Compared to mice transplanted with leukemia cells expressing original ST6Gal1 levels, increased ST6Gal1 expression was associated with significantly reduced survival. 35371997 4 7 theme B 670:670 arg1 cells 672:676 B cells 670:676 B cells 670:676 Expression of ST6Gal1 increases as B cells undergo normal B-lineage differentiation. 35371997 10 8 theme shorter 1625:1631 arg1 survival 1633:1640 shorter survival 1625:1640 shorter survival 1625:1640 Upon vincristine discontinuation, relapse was detected in both groups, but mice transplanted with ST6Gal1 overexpressing BCP-ALL cells had an increased leukemia burden and shorter survival than controls. 35371997 11 9 theme vincristine 1728:1738 arg1 treatment 1740:1748 long-term vincristine treatment 1718:1748 long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells 1718:1821 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 0 10 theme Multi-Faceted 0:12 arg1 Effects 14:20 Multi-Faceted Effects 0:20 Multi-Faceted Effects of ST6Gal1 Expression on Precursor B-Lineage Acute Lymphoblastic Leukemia 0:94 Multi-Faceted Effects of ST6Gal1 Expression on Precursor B-Lineage Acute Lymphoblastic Leukemia. 35371997 15 11 theme BCP-ALL 2295:2301 arg1 cells 2303:2307 BCP-ALL cells 2295:2307 BCP-ALL cells 2295:2307 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 15 12 theme expression 2281:2290 arg1 effect 2263:2268 a context-dependent effect 2243:2268 a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates 2243:2420 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 8 13 theme increased 1247:1255 arg1 expression 1265:1274 increased ST6Gal1 expression 1247:1274 increased ST6Gal1 expression 1247:1274 Compared to mice transplanted with leukemia cells expressing original ST6Gal1 levels, increased ST6Gal1 expression was associated with significantly reduced survival. 35371997 15 14 link N-linked 2389:2396 arg1 substrates 2411:2420 many N-linked glycoprotein substrates 2384:2420 many N-linked glycoprotein substrates 2384:2420 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 5 15 theme precursor 727:735 arg1 BCP-ALLs 768:775 BCP-ALLs 768:775 BCP-ALLs 768:775 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 5 15 theme precursor 727:735 arg1 leukemias 757:765 B-cell precursor acute lymphoblastic leukemias 720:765 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development 720:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 5 16 theme expression 874:883 arg1 levels 885:890 widely different expression levels 857:890 widely different expression levels of ST6GAL1 857:901 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 12 17 theme BCP-ALL 2025:2031 arg1 cells 2033:2037 BCP-ALL cells 2025:2037 BCP-ALL cells 2025:2037 Gene expression analysis using RNA-seq showed a surprisingly large number of genes with significantly differential expression, of which approximately 60% increased mRNAs, in the ST6Gal1 overexpressing BCP-ALL cells. 35371997 5 18 contain have 852:855 arg1 BCP-ALLs 768:775 BCP-ALLs 768:775 BCP-ALLs 768:775 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 5 18 contain have 852:855 arg1 leukemias 757:765 B-cell precursor acute lymphoblastic leukemias 720:765 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development 720:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 5 18 contain have 852:855 arg2 levels 885:890 widely different expression levels 857:890 widely different expression levels of ST6GAL1 857:901 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 5 19 theme lymphoblastic 743:755 arg1 BCP-ALLs 768:775 BCP-ALLs 768:775 BCP-ALLs 768:775 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 5 19 theme lymphoblastic 743:755 arg1 leukemias 757:765 B-cell precursor acute lymphoblastic leukemias 720:765 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development 720:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 15 20 theme context-dependent 2245:2261 arg1 effect 2263:2268 a context-dependent effect 2243:2268 a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates 2243:2420 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 5 21 with leukemias 757:765 arg1 arrest 799:804 differentiation arrest 783:804 differentiation arrest at various stages of early B-cell development 783:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 7 22 theme NSG 1085:1087 arg1 mice 1089:1092 NSG mice 1085:1092 NSG mice transplanted with these BCP-ALL cells 1085:1130 NSG mice transplanted with these BCP-ALL cells were monitored for survival. 35371997 1 23 from elements 209:216 arg1 instructions 191:202 instructions 191:202 instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix 191:339 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 1 23 from elements 209:216 arg1 microenvironment 226:241 that microenvironment 221:241 that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix 221:339 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 4 24 theme B-lineage 693:701 arg1 differentiation 703:717 normal B-lineage differentiation 686:717 normal B-lineage differentiation 686:717 Expression of ST6Gal1 increases as B cells undergo normal B-lineage differentiation. 35371997 3 25 from α2-6-linkage 581:592 arg1 addition 550:557 the terminal addition 537:557 the terminal addition of sialic acids in an α2-6-linkage to galactose 537:605 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 11 26 theme marrow 1802:1807 arg1 cells 1817:1821 OP9 bone marrow stromal cells 1793:1821 OP9 bone marrow stromal cells 1793:1821 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 0 27 theme Acute 67:71 arg1 Leukemia 87:94 Precursor B-Lineage Acute Lymphoblastic Leukemia 47:94 Precursor B-Lineage Acute Lymphoblastic Leukemia 47:94 Multi-Faceted Effects of ST6Gal1 Expression on Precursor B-Lineage Acute Lymphoblastic Leukemia. 35371997 9 28 theme mice 1340:1343 arg1 cohort 1330:1335 A cohort 1328:1335 A cohort of mice 1328:1343 A cohort of mice was also treated for 7 weeks with vincristine chemotherapy to induce remission and then allowed to relapse. 35371997 3 29 theme such 623:626 arg1 cells 628:632 such cells 623:632 such cells 623:632 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 5 30 theme high 922:925 arg1 ST6Gal1 927:933 high ST6Gal1 922:933 high ST6Gal1 in some 922:941 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 3 31 from addition 550:557 arg1 α2-6-linkage 581:592 an α2-6-linkage 578:592 an α2-6-linkage 578:592 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 5 32 from ST6Gal1 927:933 arg1 some 938:941 some 938:941 some 938:941 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 3 33 theme high 444:447 arg1 expression 449:458 high expression 444:458 high expression in specific hematopoietic cell types 444:495 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 5 34 theme development 840:850 arg1 stages 817:822 various stages 809:822 various stages of early B-cell development 809:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 9 35 theme vincristine 1379:1389 arg1 chemotherapy 1391:1402 vincristine chemotherapy 1379:1402 vincristine chemotherapy 1379:1402 A cohort of mice was also treated for 7 weeks with vincristine chemotherapy to induce remission and then allowed to relapse. 35371997 1 36 from development 123:133 arg1 marrow 173:178 the bone marrow 164:178 the bone marrow 164:178 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 1 37 theme early 104:108 arg1 development 123:133 Normal early human B-cell development 97:133 Normal early human B-cell development from lymphoid progenitors in the bone marrow 97:178 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 1 38 theme B-cell 116:121 arg1 development 123:133 Normal early human B-cell development 97:133 Normal early human B-cell development from lymphoid progenitors in the bone marrow 97:178 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 11 39 theme co-culture 1771:1780 arg1 model 1782:1786 an ex vivo tissue co-culture model 1753:1786 an ex vivo tissue co-culture model 1753:1786 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 3 40 from N-glycans 610:618 arg1 cells 628:632 such cells 623:632 such cells 623:632 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 3 41 theme hematopoietic 472:484 arg1 types 491:495 specific hematopoietic cell types 463:495 specific hematopoietic cell types 463:495 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 0 42 theme Expression 33:42 arg1 Effects 14:20 Multi-Faceted Effects 0:20 Multi-Faceted Effects of ST6Gal1 Expression on Precursor B-Lineage Acute Lymphoblastic Leukemia 0:94 Multi-Faceted Effects of ST6Gal1 Expression on Precursor B-Lineage Acute Lymphoblastic Leukemia. 35371997 1 43 theme extracellular 320:332 arg1 matrix 334:339 the extracellular matrix 316:339 the extracellular matrix 316:339 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 6 44 theme lentiviral 1060:1069 arg1 transduction 1071:1082 lentiviral transduction 1060:1082 lentiviral transduction 1060:1082 We analyzed the consequences of increasing ST6Gal1 expression in a diagnosis sample using lentiviral transduction. 35371997 3 45 theme sialyltransferase 412:428 arg1 ST6Gal1 430:436 The sialyltransferase ST6Gal1 408:436 The sialyltransferase ST6Gal1 408:436 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 3 45 theme sialyltransferase 412:428 arg1 enzyme 510:515 the only enzyme 501:515 the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells 501:632 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 15 46 theme activity 2357:2364 arg1 framework 2340:2348 the framework 2336:2348 the framework of its activity as an enzyme with many N-linked glycoprotein substrates 2336:2420 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 5 47 theme differentiation 783:797 arg1 arrest 799:804 differentiation arrest 783:804 differentiation arrest at various stages of early B-cell development 783:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 3 48 theme only 505:508 arg1 ST6Gal1 430:436 The sialyltransferase ST6Gal1 408:436 The sialyltransferase ST6Gal1 408:436 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 3 48 theme only 505:508 arg1 enzyme 510:515 the only enzyme 501:515 the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells 501:632 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 5 49 theme early 827:831 arg1 development 840:850 early B-cell development 827:850 early B-cell development 827:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 12 50 theme genes 1901:1905 arg1 number 1891:1896 a surprisingly large number 1870:1896 a surprisingly large number 1870:1896 Gene expression analysis using RNA-seq showed a surprisingly large number of genes with significantly differential expression, of which approximately 60% increased mRNAs, in the ST6Gal1 overexpressing BCP-ALL cells. 35371997 14 51 theme ST6Gal1 2136:2142 arg1 cells 2154:2158 ST6Gal1 knockdown cells 2136:2158 ST6Gal1 knockdown cells 2136:2158 However, ST6Gal1 knockdown cells also showed increased insensitivity to chemotherapy. 35371997 11 52 theme bone 1797:1800 arg1 cells 1817:1821 OP9 bone marrow stromal cells 1793:1821 OP9 bone marrow stromal cells 1793:1821 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 11 53 with treatment 1740:1748 arg1 cells 1817:1821 OP9 bone marrow stromal cells 1793:1821 OP9 bone marrow stromal cells 1793:1821 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 11 54 dep ex 1756:1757 arg1 vivo 1759:1762 vivo 1759:1762 vivo 1759:1762 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 12 55 theme differential 1926:1937 arg1 expression 1939:1948 significantly differential expression 1912:1948 significantly differential expression 1912:1948 Gene expression analysis using RNA-seq showed a surprisingly large number of genes with significantly differential expression, of which approximately 60% increased mRNAs, in the ST6Gal1 overexpressing BCP-ALL cells. 35371997 13 56 theme cell 2111:2114 arg1 migration 2116:2124 immune cell migration 2104:2124 immune cell migration 2104:2124 Pathways significantly downregulated included those involved in immune cell migration. 35371997 3 57 from expression 449:458 arg1 types 491:495 specific hematopoietic cell types 463:495 specific hematopoietic cell types 463:495 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 1 58 theme stromal 256:262 arg1 cells 264:268 stromal cells 256:268 stromal cells 256:268 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 10 59 theme leukemia 1605:1612 arg1 burden 1614:1619 an increased leukemia burden 1592:1619 an increased leukemia burden 1592:1619 Upon vincristine discontinuation, relapse was detected in both groups, but mice transplanted with ST6Gal1 overexpressing BCP-ALL cells had an increased leukemia burden and shorter survival than controls. 35371997 11 60 theme long-term 1718:1726 arg1 treatment 1740:1748 long-term vincristine treatment 1718:1748 long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells 1718:1821 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 11 61 theme higher 1680:1685 arg1 ST6Gal1 1687:1693 higher ST6Gal1 1680:1693 higher ST6Gal1 1680:1693 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 2 62 theme key 377:379 arg1 role 381:384 a key role 375:384 a key role 375:384 Glycosylation is thought to play a key role in such interactions. 35371997 12 63 theme expression 1829:1838 arg1 analysis 1840:1847 Gene expression analysis 1824:1847 Gene expression analysis using RNA-seq 1824:1861 Gene expression analysis using RNA-seq showed a surprisingly large number of genes with significantly differential expression, of which approximately 60% increased mRNAs, in the ST6Gal1 overexpressing BCP-ALL cells. 35371997 15 64 theme N-linked 2389:2396 arg1 substrates 2411:2420 many N-linked glycoprotein substrates 2384:2420 many N-linked glycoprotein substrates 2384:2420 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 8 65 theme leukemia 1196:1203 arg1 cells 1205:1209 leukemia cells 1196:1209 leukemia cells expressing original ST6Gal1 levels 1196:1244 Compared to mice transplanted with leukemia cells expressing original ST6Gal1 levels, increased ST6Gal1 expression was associated with significantly reduced survival. 35371997 3 66 with ST6Gal1 430:436 arg1 expression 449:458 high expression 444:458 high expression in specific hematopoietic cell types 444:495 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 11 67 with cells 1669:1673 arg1 ST6Gal1 1687:1693 higher ST6Gal1 1680:1693 higher ST6Gal1 1680:1693 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 3 68 theme terminal 541:548 arg1 addition 550:557 the terminal addition 537:557 the terminal addition of sialic acids in an α2-6-linkage to galactose 537:605 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 5 69 theme ST6GAL1 895:901 arg1 levels 885:890 widely different expression levels 857:890 widely different expression levels of ST6GAL1 857:901 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 0 70 theme Precursor 47:55 arg1 Leukemia 87:94 Precursor B-Lineage Acute Lymphoblastic Leukemia 47:94 Precursor B-Lineage Acute Lymphoblastic Leukemia 47:94 Multi-Faceted Effects of ST6Gal1 Expression on Precursor B-Lineage Acute Lymphoblastic Leukemia. 35371997 7 71 theme BCP-ALL 1118:1124 arg1 cells 1126:1130 these BCP-ALL cells 1112:1130 these BCP-ALL cells 1112:1130 NSG mice transplanted with these BCP-ALL cells were monitored for survival. 35371997 15 72 with enzyme 2372:2377 arg1 substrates 2411:2420 many N-linked glycoprotein substrates 2384:2420 many N-linked glycoprotein substrates 2384:2420 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 15 73 theme ST6Gal1 2273:2279 arg1 expression 2281:2290 ST6Gal1 expression 2273:2290 ST6Gal1 expression 2273:2290 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 8 74 theme ST6Gal1 1231:1237 arg1 levels 1239:1244 original ST6Gal1 levels 1222:1244 original ST6Gal1 levels 1222:1244 Compared to mice transplanted with leukemia cells expressing original ST6Gal1 levels, increased ST6Gal1 expression was associated with significantly reduced survival. 35371997 8 75 theme reduced 1310:1316 arg1 survival 1318:1325 significantly reduced survival 1296:1325 significantly reduced survival 1296:1325 Compared to mice transplanted with leukemia cells expressing original ST6Gal1 levels, increased ST6Gal1 expression was associated with significantly reduced survival. 35371997 5 76 theme B-cell 720:725 arg1 BCP-ALLs 768:775 BCP-ALLs 768:775 BCP-ALLs 768:775 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 5 76 theme B-cell 720:725 arg1 leukemias 757:765 B-cell precursor acute lymphoblastic leukemias 720:765 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development 720:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 10 77 theme vincristine 1458:1468 arg1 discontinuation 1470:1484 vincristine discontinuation 1458:1484 vincristine discontinuation 1458:1484 Upon vincristine discontinuation, relapse was detected in both groups, but mice transplanted with ST6Gal1 overexpressing BCP-ALL cells had an increased leukemia burden and shorter survival than controls. 35371997 3 78 theme acids 569:573 arg1 addition 550:557 the terminal addition 537:557 the terminal addition of sialic acids in an α2-6-linkage to galactose 537:605 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 5 79 theme different 864:872 arg1 levels 885:890 widely different expression levels 857:890 widely different expression levels of ST6GAL1 857:901 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 5 80 theme acute 737:741 arg1 BCP-ALLs 768:775 BCP-ALLs 768:775 BCP-ALLs 768:775 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 5 80 theme acute 737:741 arg1 leukemias 757:765 B-cell precursor acute lymphoblastic leukemias 720:765 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development 720:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 8 81 theme ST6Gal1 1257:1263 arg1 expression 1265:1274 increased ST6Gal1 expression 1247:1274 increased ST6Gal1 expression 1247:1274 Compared to mice transplanted with leukemia cells expressing original ST6Gal1 levels, increased ST6Gal1 expression was associated with significantly reduced survival. 35371997 10 82 located detected 1499:1506 arg2 relapse 1487:1493 relapse 1487:1493 relapse 1487:1493 Upon vincristine discontinuation, relapse was detected in both groups, but mice transplanted with ST6Gal1 overexpressing BCP-ALL cells had an increased leukemia burden and shorter survival than controls. 35371997 10 82 located detected 1499:1506 arg1 groups 1516:1521 both groups 1511:1521 both groups 1511:1521 Upon vincristine discontinuation, relapse was detected in both groups, but mice transplanted with ST6Gal1 overexpressing BCP-ALL cells had an increased leukemia burden and shorter survival than controls. 35371997 10 83 contain had 1588:1590 arg2 survival 1633:1640 shorter survival 1625:1640 shorter survival 1625:1640 Upon vincristine discontinuation, relapse was detected in both groups, but mice transplanted with ST6Gal1 overexpressing BCP-ALL cells had an increased leukemia burden and shorter survival than controls. 35371997 10 83 contain had 1588:1590 arg2 burden 1614:1619 an increased leukemia burden 1592:1619 an increased leukemia burden 1592:1619 Upon vincristine discontinuation, relapse was detected in both groups, but mice transplanted with ST6Gal1 overexpressing BCP-ALL cells had an increased leukemia burden and shorter survival than controls. 35371997 10 83 contain had 1588:1590 arg1 mice 1528:1531 mice 1528:1531 mice transplanted with ST6Gal1 overexpressing BCP-ALL cells 1528:1586 Upon vincristine discontinuation, relapse was detected in both groups, but mice transplanted with ST6Gal1 overexpressing BCP-ALL cells had an increased leukemia burden and shorter survival than controls. 35371997 15 84 from effect 2263:2268 arg1 cells 2303:2307 BCP-ALL cells 2295:2307 BCP-ALL cells 2295:2307 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 3 85 from acids 569:573 arg1 α2-6-linkage 581:592 an α2-6-linkage 578:592 an α2-6-linkage 578:592 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 1 86 theme lymphoid 140:147 arg1 progenitors 149:159 lymphoid progenitors 140:159 lymphoid progenitors 140:159 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 12 87 with genes 1901:1905 arg1 expression 1939:1948 significantly differential expression 1912:1948 significantly differential expression 1912:1948 Gene expression analysis using RNA-seq showed a surprisingly large number of genes with significantly differential expression, of which approximately 60% increased mRNAs, in the ST6Gal1 overexpressing BCP-ALL cells. 35371997 0 88 theme Lymphoblastic 73:85 arg1 Leukemia 87:94 Precursor B-Lineage Acute Lymphoblastic Leukemia 47:94 Precursor B-Lineage Acute Lymphoblastic Leukemia 47:94 Multi-Faceted Effects of ST6Gal1 Expression on Precursor B-Lineage Acute Lymphoblastic Leukemia. 35371997 6 89 theme diagnosis 1037:1045 arg1 sample 1047:1052 a diagnosis sample 1035:1052 a diagnosis sample using lentiviral transduction 1035:1082 We analyzed the consequences of increasing ST6Gal1 expression in a diagnosis sample using lentiviral transduction. 35371997 4 90 theme normal 686:691 arg1 differentiation 703:717 normal B-lineage differentiation 686:717 normal B-lineage differentiation 686:717 Expression of ST6Gal1 increases as B cells undergo normal B-lineage differentiation. 35371997 11 91 theme stromal 1809:1815 arg1 cells 1817:1821 OP9 bone marrow stromal cells 1793:1821 OP9 bone marrow stromal cells 1793:1821 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 1 92 theme bone 168:171 arg1 marrow 173:178 the bone marrow 164:178 the bone marrow 164:178 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 0 93 from Effects 14:20 arg1 Leukemia 87:94 Precursor B-Lineage Acute Lymphoblastic Leukemia 47:94 Precursor B-Lineage Acute Lymphoblastic Leukemia 47:94 Multi-Faceted Effects of ST6Gal1 Expression on Precursor B-Lineage Acute Lymphoblastic Leukemia. 35371997 5 94 from stages 817:822 arg1 arrest 799:804 differentiation arrest 783:804 differentiation arrest at various stages of early B-cell development 783:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 6 95 theme ST6Gal1 1013:1019 arg1 expression 1021:1030 ST6Gal1 expression 1013:1030 ST6Gal1 expression in a diagnosis sample using lentiviral transduction 1013:1082 We analyzed the consequences of increasing ST6Gal1 expression in a diagnosis sample using lentiviral transduction. 35371997 15 96 gly glycoprotein 2398:2409 arg1 glycoprotein 2398:2409 many N-linked glycoprotein substrates 2384:2420 many N-linked glycoprotein substrates 2384:2420 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 3 97 theme specific 463:470 arg1 types 491:495 specific hematopoietic cell types 463:495 specific hematopoietic cell types 463:495 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 5 98 theme B-cell 833:838 arg1 development 840:850 early B-cell development 827:850 early B-cell development 827:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 1 99 from progenitors 149:159 arg1 development 123:133 Normal early human B-cell development 97:133 Normal early human B-cell development from lymphoid progenitors in the bone marrow 97:178 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 5 100 theme other 954:958 arg1 relapses 960:967 other relapses 954:967 other relapses 954:967 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 11 101 from treatment 1740:1748 arg1 model 1782:1786 an ex vivo tissue co-culture model 1753:1786 an ex vivo tissue co-culture model 1753:1786 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 6 102 from expression 1021:1030 arg1 sample 1047:1052 a diagnosis sample 1035:1052 a diagnosis sample using lentiviral transduction 1035:1082 We analyzed the consequences of increasing ST6Gal1 expression in a diagnosis sample using lentiviral transduction. 35371997 2 103 theme such 389:392 arg1 interactions 394:405 such interactions 389:405 such interactions 389:405 Glycosylation is thought to play a key role in such interactions. 35371997 0 104 theme ST6Gal1 25:31 arg1 Expression 33:42 ST6Gal1 Expression 25:42 ST6Gal1 Expression 25:42 Multi-Faceted Effects of ST6Gal1 Expression on Precursor B-Lineage Acute Lymphoblastic Leukemia. 35371997 15 105 theme many 2384:2387 arg1 substrates 2411:2420 many N-linked glycoprotein substrates 2384:2420 many N-linked glycoprotein substrates 2384:2420 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 1 106 theme human 110:114 arg1 development 123:133 Normal early human B-cell development 97:133 Normal early human B-cell development from lymphoid progenitors in the bone marrow 97:178 Normal early human B-cell development from lymphoid progenitors in the bone marrow depends on instructions from elements in that microenvironment that include stromal cells and factors secreted by these cells including the extracellular matrix. 35371997 14 107 theme increased 2172:2180 arg1 insensitivity 2182:2194 increased insensitivity 2172:2194 increased insensitivity to chemotherapy 2172:2210 However, ST6Gal1 knockdown cells also showed increased insensitivity to chemotherapy. 35371997 11 108 theme tissue 1764:1769 arg1 model 1782:1786 an ex vivo tissue co-culture model 1753:1786 an ex vivo tissue co-culture model 1753:1786 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 5 109 theme various 809:815 arg1 stages 817:822 various stages 809:822 various stages of early B-cell development 809:850 B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) with differentiation arrest at various stages of early B-cell development have widely different expression levels of ST6GAL1 at diagnosis, with high ST6Gal1 in some but not in other relapses. 35371997 11 110 theme ex 1756:1757 arg1 model 1782:1786 an ex vivo tissue co-culture model 1753:1786 an ex vivo tissue co-culture model 1753:1786 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 11 111 theme BCP-ALL 1661:1667 arg1 cells 1669:1673 The BCP-ALL cells 1657:1673 The BCP-ALL cells with higher ST6Gal1 1657:1693 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 11 111 theme BCP-ALL 1661:1667 arg1 resistant 1705:1713 resistant 1705:1713 resistant 1705:1713 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 3 112 theme cell 486:489 arg1 types 491:495 specific hematopoietic cell types 463:495 specific hematopoietic cell types 463:495 The sialyltransferase ST6Gal1, with high expression in specific hematopoietic cell types, is the only enzyme thought to catalyze the terminal addition of sialic acids in an α2-6-linkage to galactose on N-glycans in such cells. 35371997 0 113 theme B-Lineage 57:65 arg1 Leukemia 87:94 Precursor B-Lineage Acute Lymphoblastic Leukemia 47:94 Precursor B-Lineage Acute Lymphoblastic Leukemia 47:94 Multi-Faceted Effects of ST6Gal1 Expression on Precursor B-Lineage Acute Lymphoblastic Leukemia. 35371997 15 114 theme combined 2217:2224 arg1 results 2226:2232 Our combined results 2213:2232 Our combined results 2213:2232 Our combined results point to a context-dependent effect of ST6Gal1 expression on BCP-ALL cells, which is discussed within the framework of its activity as an enzyme with many N-linked glycoprotein substrates. 35371997 12 115 theme large 1885:1889 arg1 number 1891:1896 a surprisingly large number 1870:1896 a surprisingly large number 1870:1896 Gene expression analysis using RNA-seq showed a surprisingly large number of genes with significantly differential expression, of which approximately 60% increased mRNAs, in the ST6Gal1 overexpressing BCP-ALL cells. 35371997 14 116 theme knockdown 2144:2152 arg1 cells 2154:2158 ST6Gal1 knockdown cells 2136:2158 ST6Gal1 knockdown cells 2136:2158 However, ST6Gal1 knockdown cells also showed increased insensitivity to chemotherapy. 35371997 11 117 theme OP9 1793:1795 arg1 cells 1817:1821 OP9 bone marrow stromal cells 1793:1821 OP9 bone marrow stromal cells 1793:1821 The BCP-ALL cells with higher ST6Gal1 were more resistant to long-term vincristine treatment in an ex vivo tissue co-culture model with OP9 bone marrow stromal cells. 35371997 10 118 theme BCP-ALL 1574:1580 arg1 cells 1582:1586 BCP-ALL cells 1574:1586 BCP-ALL cells 1574:1586 Upon vincristine discontinuation, relapse was detected in both groups, but mice transplanted with ST6Gal1 overexpressing BCP-ALL cells had an increased leukemia burden and shorter survival than controls. 35371997 4 119 theme ST6Gal1 649:655 arg1 Expression 635:644 Expression 635:644 Expression of ST6Gal1 635:655 Expression of ST6Gal1 increases as B cells undergo normal B-lineage differentiation. 36066100 0 0 theme Immunocompromised 88:104 arg1 Mice 106:109 Immunocompromised Mice 88:109 Immunocompromised Mice 88:109 Vaccination with Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia Fully Protects Immunocompromised Mice from Invasive Aspergillosis. 36066100 12 1 theme safe 1767:1770 arg1 vaccine 1779:1785 a safe fungal vaccine 1765:1785 a safe fungal vaccine for protection against the environmental fungus A. fumigatus 1765:1846 These results will significantly advance the field of the research and development of a safe fungal vaccine for protection against the environmental fungus A. fumigatus. 36066100 4 2 theme immunomodulatory 606:621 arg1 glycolipids 623:633 newly studied immunomodulatory glycolipids 592:633 newly studied immunomodulatory glycolipids 592:633 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 4 2 theme immunomodulatory 606:621 arg1 sterylglucosides 568:583 sterylglucosides 568:583 sterylglucosides (SGs) 568:589 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 10 3 with challenge 1523:1531 arg1 conidia 1553:1559 live wild-type conidia 1538:1559 live wild-type conidia 1538:1559 Interestingly, these animals are now protected against a secondary challenge with live wild-type conidia. 36066100 4 4 theme ΔsglA 543:547 arg1 mutant 549:554 The ΔsglA mutant 539:554 The ΔsglA mutant 539:554 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 6 5 theme corticosteroid-induced 846:867 arg1 mice 926:929 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice 841:929 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia 841:979 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 7 6 theme invasive 1169:1176 arg1 infections 1185:1194 invasive fungal infections 1169:1194 invasive fungal infections 1169:1194 These results highlight the potential of SG-accumulating strains as safe and promising vaccine formulations against invasive fungal infections. 36066100 11 7 theme heat-killed 1651:1661 arg1 conidia 1670:1676 heat-killed mutant conidia 1651:1676 heat-killed mutant conidia 1651:1676 Remarkably, protection against a secondary challenge persists even with vaccination with heat-killed mutant conidia. 36066100 4 8 theme studied 598:604 arg1 glycolipids 623:633 newly studied immunomodulatory glycolipids 592:633 newly studied immunomodulatory glycolipids 592:633 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 4 8 theme studied 598:604 arg1 sterylglucosides 568:583 sterylglucosides 568:583 sterylglucosides (SGs) 568:589 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 8 9 theme fungal 1285:1290 arg1 spores 1292:1297 environmental fungal spores 1271:1297 environmental fungal spores called conidia 1271:1312 IMPORTANCE Infections by Aspergillus fumigatus occur by the inhalation of environmental fungal spores called conidia. 36066100 11 10 with vaccination 1634:1644 arg1 conidia 1670:1676 heat-killed mutant conidia 1651:1676 heat-killed mutant conidia 1651:1676 Remarkably, protection against a secondary challenge persists even with vaccination with heat-killed mutant conidia. 36066100 11 11 theme mutant 1663:1668 arg1 conidia 1670:1676 heat-killed mutant conidia 1651:1676 heat-killed mutant conidia 1651:1676 Remarkably, protection against a secondary challenge persists even with vaccination with heat-killed mutant conidia. 36066100 8 12 theme environmental 1271:1283 arg1 spores 1292:1297 environmental fungal spores 1271:1297 environmental fungal spores called conidia 1271:1312 IMPORTANCE Infections by Aspergillus fumigatus occur by the inhalation of environmental fungal spores called conidia. 36066100 10 13 theme secondary 1513:1521 arg1 challenge 1523:1531 a secondary challenge 1511:1531 a secondary challenge with live wild-type conidia 1511:1559 Interestingly, these animals are now protected against a secondary challenge with live wild-type conidia. 36066100 2 14 theme immune 309:314 arg1 protection 316:325 immune protection 309:325 immune protection 309:325 Currently, no vaccine formulations to promote immune protection in at-risk individuals have been developed. 36066100 5 15 theme murine 780:785 arg1 models 787:792 two murine models 776:792 two murine models of IA 776:798 Interestingly, the ΔsglA mutant was avirulent in two murine models of IA and was fully eliminated from the lungs. 36066100 6 16 theme ΔsglA 967:971 arg1 conidia 973:979 live or heat-killed ΔsglA conidia 947:979 live or heat-killed ΔsglA conidia 947:979 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 1 17 from aspergillosis 178:190 arg1 patients 218:225 immunocompromised patients 200:225 immunocompromised patients 200:225 Aspergillus fumigatus causes invasive aspergillosis (IA) in immunocompromised patients, resulting in high mortality rates. 36066100 2 18 dep formulations 285:296 arg1 promote 301:307 promote 301:307 to promote immune protection in at-risk individuals 298:348 Currently, no vaccine formulations to promote immune protection in at-risk individuals have been developed. 36066100 4 19 theme cell 700:703 arg1 polysaccharides 710:724 cell wall polysaccharides 700:724 cell wall polysaccharides 700:724 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 0 20 theme Invasive 116:123 arg1 Aspergillosis 125:137 Invasive Aspergillosis 116:137 Invasive Aspergillosis 116:137 Vaccination with Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia Fully Protects Immunocompromised Mice from Invasive Aspergillosis. 36066100 6 21 theme heat-killed 955:965 arg1 conidia 973:979 live or heat-killed ΔsglA conidia 947:979 live or heat-killed ΔsglA conidia 947:979 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 9 22 theme named 1374:1378 arg1 sterylglucosides 1380:1395 glycolipids named sterylglucosides 1362:1395 glycolipids named sterylglucosides 1362:1395 We found that live mutant conidia accumulating glycolipids named sterylglucosides are not able to cause disease when injected into the lung. 36066100 12 23 theme development 1750:1760 arg1 field 1724:1728 the field 1720:1728 the field of the research and development of a safe fungal vaccine for protection against the environmental fungus A. fumigatus 1720:1846 These results will significantly advance the field of the research and development of a safe fungal vaccine for protection against the environmental fungus A. fumigatus. 36066100 3 24 theme sterylglucosidase-encoding 400:425 arg1 sglA 433:436 sglA 433:436 sglA 433:436 In this work, we deleted the sterylglucosidase-encoding gene, sglA, in Aspergillus fumigatus and investigated its role in fungal virulence and host vaccine protection. 36066100 3 24 theme sterylglucosidase-encoding 400:425 arg1 gene 427:430 the sterylglucosidase-encoding gene 396:430 the sterylglucosidase-encoding gene 396:430 In this work, we deleted the sterylglucosidase-encoding gene, sglA, in Aspergillus fumigatus and investigated its role in fungal virulence and host vaccine protection. 36066100 3 25 from gene 427:430 arg1 fumigatus 454:462 Aspergillus fumigatus 442:462 Aspergillus fumigatus 442:462 In this work, we deleted the sterylglucosidase-encoding gene, sglA, in Aspergillus fumigatus and investigated its role in fungal virulence and host vaccine protection. 36066100 9 26 theme live 1329:1332 arg1 conidia 1341:1347 live mutant conidia 1329:1347 live mutant conidia accumulating glycolipids named sterylglucosides 1329:1395 We found that live mutant conidia accumulating glycolipids named sterylglucosides are not able to cause disease when injected into the lung. 36066100 12 27 dep safe 1767:1770 arg1 fungal 1772:1777 fungal 1772:1777 fungal 1772:1777 These results will significantly advance the field of the research and development of a safe fungal vaccine for protection against the environmental fungus A. fumigatus. 36066100 1 28 theme immunocompromised 200:216 arg1 patients 218:225 immunocompromised patients 200:225 immunocompromised patients 200:225 Aspergillus fumigatus causes invasive aspergillosis (IA) in immunocompromised patients, resulting in high mortality rates. 36066100 12 29 dep research 1737:1744 arg1 the 1733:1735 the 1733:1735 the 1733:1735 These results will significantly advance the field of the research and development of a safe fungal vaccine for protection against the environmental fungus A. fumigatus. 36066100 6 30 theme immunosuppressed 869:884 arg1 mice 926:929 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice 841:929 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia 841:979 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 9 31 theme mutant 1334:1339 arg1 conidia 1341:1347 live mutant conidia 1329:1347 live mutant conidia accumulating glycolipids named sterylglucosides 1329:1395 We found that live mutant conidia accumulating glycolipids named sterylglucosides are not able to cause disease when injected into the lung. 36066100 4 32 theme wall 705:708 arg1 polysaccharides 710:724 cell wall polysaccharides 700:724 cell wall polysaccharides 700:724 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 8 33 theme spores 1292:1297 arg1 inhalation 1257:1266 the inhalation 1253:1266 the inhalation of environmental fungal spores called conidia 1253:1312 IMPORTANCE Infections by Aspergillus fumigatus occur by the inhalation of environmental fungal spores called conidia. 36066100 5 34 theme ΔsglA 746:750 arg1 mutant 752:757 the ΔsglA mutant 742:757 the ΔsglA mutant 742:757 Interestingly, the ΔsglA mutant was avirulent in two murine models of IA and was fully eliminated from the lungs. 36066100 5 34 theme ΔsglA 746:750 arg1 avirulent 763:771 avirulent 763:771 avirulent 763:771 Interestingly, the ΔsglA mutant was avirulent in two murine models of IA and was fully eliminated from the lungs. 36066100 10 35 theme live 1538:1541 arg1 conidia 1553:1559 live wild-type conidia 1538:1559 live wild-type conidia 1538:1559 Interestingly, these animals are now protected against a secondary challenge with live wild-type conidia. 36066100 2 36 theme at-risk 330:336 arg1 individuals 338:348 at-risk individuals 330:348 at-risk individuals 330:348 Currently, no vaccine formulations to promote immune protection in at-risk individuals have been developed. 36066100 12 37 theme vaccine 1779:1785 arg1 development 1750:1760 development 1750:1760 development 1750:1760 These results will significantly advance the field of the research and development of a safe fungal vaccine for protection against the environmental fungus A. fumigatus. 36066100 12 37 theme vaccine 1779:1785 arg1 research 1737:1744 research 1737:1744 research 1737:1744 These results will significantly advance the field of the research and development of a safe fungal vaccine for protection against the environmental fungus A. fumigatus. 36066100 0 38 theme Live 17:20 arg1 Conidia 65:71 Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia 17:71 Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia 17:71 Vaccination with Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia Fully Protects Immunocompromised Mice from Invasive Aspergillosis. 36066100 7 39 theme fungal 1178:1183 arg1 infections 1185:1194 invasive fungal infections 1169:1194 invasive fungal infections 1169:1194 These results highlight the potential of SG-accumulating strains as safe and promising vaccine formulations against invasive fungal infections. 36066100 6 40 theme live 947:950 arg1 conidia 973:979 live or heat-killed ΔsglA conidia 947:979 live or heat-killed ΔsglA conidia 947:979 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 3 41 theme fungal 493:498 arg1 virulence 500:508 fungal virulence 493:508 fungal virulence 493:508 In this work, we deleted the sterylglucosidase-encoding gene, sglA, in Aspergillus fumigatus and investigated its role in fungal virulence and host vaccine protection. 36066100 0 42 theme Aspergillus 37:47 arg1 Conidia 65:71 Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia 17:71 Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia 17:71 Vaccination with Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia Fully Protects Immunocompromised Mice from Invasive Aspergillosis. 36066100 3 43 theme vaccine 519:525 arg1 protection 527:536 host vaccine protection 514:536 host vaccine protection 514:536 In this work, we deleted the sterylglucosidase-encoding gene, sglA, in Aspergillus fumigatus and investigated its role in fungal virulence and host vaccine protection. 36066100 5 44 from models 787:792 arg1 mutant 752:757 the ΔsglA mutant 742:757 the ΔsglA mutant 742:757 Interestingly, the ΔsglA mutant was avirulent in two murine models of IA and was fully eliminated from the lungs. 36066100 5 44 from models 787:792 arg1 avirulent 763:771 avirulent 763:771 avirulent 763:771 Interestingly, the ΔsglA mutant was avirulent in two murine models of IA and was fully eliminated from the lungs. 36066100 11 45 theme secondary 1595:1603 arg1 challenge 1605:1613 a secondary challenge 1593:1613 a secondary challenge 1593:1613 Remarkably, protection against a secondary challenge persists even with vaccination with heat-killed mutant conidia. 36066100 0 46 theme Heat-Killed 25:35 arg1 Conidia 65:71 Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia 17:71 Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia 17:71 Vaccination with Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia Fully Protects Immunocompromised Mice from Invasive Aspergillosis. 36066100 6 47 theme A. 1029:1030 arg1 challenge 1042:1050 a lethal wild-type A. fumigatus challenge 1010:1050 a lethal wild-type A. fumigatus challenge 1010:1050 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 5 48 from avirulent 763:771 arg1 models 787:792 two murine models 776:792 two murine models of IA 776:798 Interestingly, the ΔsglA mutant was avirulent in two murine models of IA and was fully eliminated from the lungs. 36066100 6 49 dep A. 1029:1030 arg1 fumigatus 1032:1040 fumigatus 1032:1040 fumigatus 1032:1040 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 7 50 theme strains 1110:1116 arg1 potential 1081:1089 the potential 1077:1089 the potential of SG-accumulating strains as safe and promising vaccine formulations against invasive fungal infections 1077:1194 These results highlight the potential of SG-accumulating strains as safe and promising vaccine formulations against invasive fungal infections. 36066100 1 51 theme high 241:244 arg1 rates 256:260 high mortality rates 241:260 high mortality rates 241:260 Aspergillus fumigatus causes invasive aspergillosis (IA) in immunocompromised patients, resulting in high mortality rates. 36066100 0 52 theme ΔsglA 59:63 arg1 Conidia 65:71 Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia 17:71 Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia 17:71 Vaccination with Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia Fully Protects Immunocompromised Mice from Invasive Aspergillosis. 36066100 4 53 theme polysaccharides 710:724 arg1 growth 665:670 reduced hyphal growth 650:670 reduced hyphal growth 650:670 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 4 53 theme polysaccharides 710:724 arg1 compositions 684:695 altered compositions 676:695 altered compositions 676:695 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 7 54 theme promising 1130:1138 arg1 formulations 1148:1159 safe and promising vaccine formulations 1121:1159 safe and promising vaccine formulations against invasive fungal infections 1121:1194 These results highlight the potential of SG-accumulating strains as safe and promising vaccine formulations against invasive fungal infections. 36066100 0 55 dep Aspergillus 37:47 arg1 fumigatus 49:57 fumigatus 49:57 fumigatus 49:57 Vaccination with Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia Fully Protects Immunocompromised Mice from Invasive Aspergillosis. 36066100 3 56 from role 485:488 arg1 virulence 500:508 fungal virulence 493:508 fungal virulence 493:508 In this work, we deleted the sterylglucosidase-encoding gene, sglA, in Aspergillus fumigatus and investigated its role in fungal virulence and host vaccine protection. 36066100 3 56 from role 485:488 arg1 protection 527:536 host vaccine protection 514:536 host vaccine protection 514:536 In this work, we deleted the sterylglucosidase-encoding gene, sglA, in Aspergillus fumigatus and investigated its role in fungal virulence and host vaccine protection. 36066100 3 57 theme host 514:517 arg1 protection 527:536 host vaccine protection 514:536 host vaccine protection 514:536 In this work, we deleted the sterylglucosidase-encoding gene, sglA, in Aspergillus fumigatus and investigated its role in fungal virulence and host vaccine protection. 36066100 8 58 theme IMPORTANCE 1197:1206 arg1 Infections 1208:1217 IMPORTANCE Infections 1197:1217 IMPORTANCE Infections by Aspergillus fumigatus 1197:1242 IMPORTANCE Infections by Aspergillus fumigatus occur by the inhalation of environmental fungal spores called conidia. 36066100 6 59 theme lethal 1012:1017 arg1 challenge 1042:1050 a lethal wild-type A. fumigatus challenge 1010:1050 a lethal wild-type A. fumigatus challenge 1010:1050 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 7 60 theme vaccine 1140:1146 arg1 formulations 1148:1159 safe and promising vaccine formulations 1121:1159 safe and promising vaccine formulations against invasive fungal infections 1121:1194 These results highlight the potential of SG-accumulating strains as safe and promising vaccine formulations against invasive fungal infections. 36066100 6 61 theme leukopenic 915:924 arg1 mice 926:929 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice 841:929 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia 841:979 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 10 62 theme wild-type 1543:1551 arg1 conidia 1553:1559 live wild-type conidia 1538:1559 live wild-type conidia 1538:1559 Interestingly, these animals are now protected against a secondary challenge with live wild-type conidia. 36066100 1 63 theme Aspergillus 140:150 arg1 fumigatus 152:160 Aspergillus fumigatus 140:160 Aspergillus fumigatus 140:160 Aspergillus fumigatus causes invasive aspergillosis (IA) in immunocompromised patients, resulting in high mortality rates. 36066100 7 64 theme safe 1121:1124 arg1 formulations 1148:1159 safe and promising vaccine formulations 1121:1159 safe and promising vaccine formulations against invasive fungal infections 1121:1194 These results highlight the potential of SG-accumulating strains as safe and promising vaccine formulations against invasive fungal infections. 36066100 6 65 theme cyclophosphamide-induced 890:913 arg1 mice 926:929 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice 841:929 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia 841:979 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 0 66 with Vaccination 0:10 arg1 Conidia 65:71 Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia 17:71 Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia 17:71 Vaccination with Live or Heat-Killed Aspergillus fumigatus ΔsglA Conidia Fully Protects Immunocompromised Mice from Invasive Aspergillosis. 36066100 1 67 theme mortality 246:254 arg1 rates 256:260 high mortality rates 241:260 high mortality rates 241:260 Aspergillus fumigatus causes invasive aspergillosis (IA) in immunocompromised patients, resulting in high mortality rates. 36066100 7 68 theme SG-accumulating 1094:1108 arg1 strains 1110:1116 SG-accumulating strains 1094:1116 SG-accumulating strains 1094:1116 These results highlight the potential of SG-accumulating strains as safe and promising vaccine formulations against invasive fungal infections. 36066100 2 69 theme vaccine 277:283 arg1 formulations 285:296 no vaccine formulations 274:296 no vaccine formulations to promote immune protection in at-risk individuals 274:348 Currently, no vaccine formulations to promote immune protection in at-risk individuals have been developed. 36066100 4 70 theme altered 676:682 arg1 compositions 684:695 altered compositions 676:695 altered compositions 676:695 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 1 71 theme invasive 169:176 arg1 aspergillosis 178:190 invasive aspergillosis 169:190 invasive aspergillosis (IA) in immunocompromised patients 169:225 Aspergillus fumigatus causes invasive aspergillosis (IA) in immunocompromised patients, resulting in high mortality rates. 36066100 1 71 theme invasive 169:176 arg1 IA 193:194 IA 193:194 IA 193:194 Aspergillus fumigatus causes invasive aspergillosis (IA) in immunocompromised patients, resulting in high mortality rates. 36066100 12 72 theme research 1737:1744 arg1 field 1724:1728 the field 1720:1728 the field of the research and development of a safe fungal vaccine for protection against the environmental fungus A. fumigatus 1720:1846 These results will significantly advance the field of the research and development of a safe fungal vaccine for protection against the environmental fungus A. fumigatus. 36066100 4 73 theme hyphal 658:663 arg1 growth 665:670 reduced hyphal growth 650:670 reduced hyphal growth 650:670 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 36066100 5 74 theme IA 797:798 arg1 models 787:792 two murine models 776:792 two murine models of IA 776:798 Interestingly, the ΔsglA mutant was avirulent in two murine models of IA and was fully eliminated from the lungs. 36066100 6 75 theme wild-type 1019:1027 arg1 challenge 1042:1050 a lethal wild-type A. fumigatus challenge 1010:1050 a lethal wild-type A. fumigatus challenge 1010:1050 Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed ΔsglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. 36066100 4 76 theme reduced 650:656 arg1 growth 665:670 reduced hyphal growth 650:670 reduced hyphal growth 650:670 The ΔsglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. 35681381 8 0 from mM 1276:1277 arg1 colon 1296:1300 the ascending colon 1282:1300 the ascending colon 1282:1300 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 0 from mM 1276:1277 arg1 colon 1337:1341 the transverse colon 1322:1341 the transverse colon 1322:1341 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 0 from mM 1276:1277 arg1 colon 1381:1385 the descending colon 1366:1385 the descending colon 1366:1385 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 1 from mM 1360:1361 arg1 colon 1296:1300 the ascending colon 1282:1300 the ascending colon 1282:1300 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 1 from mM 1360:1361 arg1 colon 1337:1341 the transverse colon 1322:1341 the transverse colon 1322:1341 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 1 from mM 1360:1361 arg1 colon 1381:1385 the descending colon 1366:1385 the descending colon 1366:1385 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 9 2 theme gut 1510:1512 arg1 modulation 1525:1534 gut microbiota modulation 1510:1534 gut microbiota modulation 1510:1534 In summary, CMPP can be considered as a pectin, showed immunological activity and function of gut microbiota modulation. 35681381 1 3 theme by-products 142:152 arg1 recycling 123:131 the recycling 119:131 the recycling of fruit by-products from kiwano 119:164 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 7 4 theme intake 1095:1100 arg1 period 1102:1107 the intake period 1091:1107 the intake period 1091:1107 During the intake period, acetic, butyric and propionic acids were all increased, especially (p < 0.05) in the descending colon. 35681381 5 5 theme necrosis 828:835 arg1 factor 837:842 tumor necrosis factor α 822:844 tumor necrosis factor α (TNF-α) 822:852 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 5 5 theme necrosis 828:835 arg1 TNF-α 847:851 TNF-α 847:851 TNF-α 847:851 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 3 6 theme gut 499:501 arg1 simulator 483:491 simulator 483:491 the microbiota dynamics simulator (BFBL gut model) 459:508 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 3 6 theme gut 499:501 arg1 model 503:507 BFBL gut model 494:507 BFBL gut model 494:507 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 8 7 from decrease 1228:1235 arg1 concentration 1248:1260 ammonia concentration 1240:1260 ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) 1240:1400 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 5 8 theme cell 689:692 arg1 proliferation 694:706 cell proliferation 689:706 cell proliferation 689:706 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 5 9 theme tumor 822:826 arg1 factor 837:842 tumor necrosis factor α 822:844 tumor necrosis factor α (TNF-α) 822:852 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 5 9 theme tumor 822:826 arg1 TNF-α 847:851 TNF-α 847:851 TNF-α 847:851 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 6 10 theme Akkermansia 1008:1018 arg1 growth 998:1003 the growth 994:1003 the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia 994:1081 In addition, CMPP had an impact on the composition of the gut bacteria, increasing the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia. 35681381 8 11 theme transverse 1326:1335 arg1 colon 1337:1341 the transverse colon 1322:1341 the transverse colon 1322:1341 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 3 12 theme in 524:525 arg1 study 533:537 in vitro study 524:537 in vitro study 524:537 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 9 13 theme immunological 1471:1483 arg1 activity 1485:1492 immunological activity 1471:1492 immunological activity 1471:1492 In summary, CMPP can be considered as a pectin, showed immunological activity and function of gut microbiota modulation. 35681381 3 14 theme BFBL 494:497 arg1 simulator 483:491 simulator 483:491 the microbiota dynamics simulator (BFBL gut model) 459:508 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 3 14 theme BFBL 494:497 arg1 model 503:507 BFBL gut model 494:507 BFBL gut model 494:507 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 1 15 theme Cucumis 246:252 arg1 polysaccharide 272:285 Cucumis metuliferus peels polysaccharide 246:285 Cucumis metuliferus peels polysaccharide (CMPP) 246:292 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 1 15 theme Cucumis 246:252 arg1 peels 232:236 kiwano (Cucumis metuliferus) peels 203:236 kiwano (Cucumis metuliferus) peels 203:236 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 1 15 theme Cucumis 246:252 arg1 CMPP 288:291 CMPP 288:291 CMPP 288:291 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 1 16 theme potential 329:337 arg1 effects 350:356 the potential beneficial effects 325:356 the potential beneficial effects 325:356 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 6 17 theme gut 969:971 arg1 bacteria 973:980 the gut bacteria 965:980 the gut bacteria 965:980 In addition, CMPP had an impact on the composition of the gut bacteria, increasing the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia. 35681381 3 18 used used 515:518 arg2 macrophages 437:447 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) 428:508 macrophages 437:447 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 3 18 used used 515:518 arg2 dynamics 474:481 the microbiota dynamics simulator (BFBL gut model) 459:508 the microbiota dynamics simulator (BFBL gut model) 459:508 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 1 19 theme beneficial 339:348 arg1 effects 350:356 the potential beneficial effects 325:356 the potential beneficial effects 325:356 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 6 20 theme Bifidobacterium 1034:1048 arg1 growth 998:1003 the growth 994:1003 the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia 994:1081 In addition, CMPP had an impact on the composition of the gut bacteria, increasing the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia. 35681381 8 21 theme ascending 1286:1294 arg1 colon 1296:1300 the ascending colon 1282:1300 the ascending colon 1282:1300 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 3 22 theme RAW264.7 428:435 arg1 macrophages 437:447 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) 428:508 macrophages 437:447 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 5 23 dep significantly 752:764 arg1 p 767:767 p 767:767 p < 0.05 767:777 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 9 24 theme microbiota 1514:1523 arg1 modulation 1525:1534 gut microbiota modulation 1510:1534 gut microbiota modulation 1510:1534 In summary, CMPP can be considered as a pectin, showed immunological activity and function of gut microbiota modulation. 35681381 6 25 contain had 929:931 arg1 CMPP 924:927 CMPP 924:927 CMPP 924:927 In addition, CMPP had an impact on the composition of the gut bacteria, increasing the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia. 35681381 6 25 contain had 929:931 arg2 impact 936:941 an impact 933:941 an impact on the composition of the gut bacteria 933:980 In addition, CMPP had an impact on the composition of the gut bacteria, increasing the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia. 35681381 0 26 theme Immunological 0:12 arg1 Activity 14:21 Immunological Activity and Gut Microbiota Modulation 0:51 Activity 14:21 Immunological Activity and Gut Microbiota Modulation of Pectin from Kiwano (Cucumis metuliferus) Peels. 35681381 1 27 theme metuliferus 254:264 arg1 polysaccharide 272:285 Cucumis metuliferus peels polysaccharide 246:285 Cucumis metuliferus peels polysaccharide (CMPP) 246:292 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 1 27 theme metuliferus 254:264 arg1 peels 232:236 kiwano (Cucumis metuliferus) peels 203:236 kiwano (Cucumis metuliferus) peels 203:236 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 1 27 theme metuliferus 254:264 arg1 CMPP 288:291 CMPP 288:291 CMPP 288:291 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 10 28 theme kiwano 1592:1597 arg1 peels 1599:1603 kiwano peels 1592:1603 kiwano peels 1592:1603 This study could be the scientific basis of developing kiwano peels as beneficial to human health. 35681381 5 29 theme oxide 810:814 arg1 release 792:798 the release 788:798 the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) 788:877 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 5 30 theme interleukin 858:868 arg1 release 792:798 the release 788:798 the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) 788:877 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 8 31 dep concentration 1248:1260 arg1 mM 1316:1317 13.21 ± 1.54 mM 1303:1317 13.21 ± 1.54 mM in the transverse colon 1303:1341 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 31 dep concentration 1248:1260 arg1 mM 1360:1361 13.62 ± 0.45 mM 1347:1361 13.62 ± 0.45 mM in the descending colon 1347:1385 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 31 dep concentration 1248:1260 arg1 mM 1276:1277 10.17 ± 0.50 mM 1263:1277 10.17 ± 0.50 mM in the ascending colon 1263:1300 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 0 32 theme Gut 27:29 arg1 Modulation 42:51 Immunological Activity and Gut Microbiota Modulation 0:51 Modulation 42:51 Immunological Activity and Gut Microbiota Modulation of Pectin from Kiwano (Cucumis metuliferus) Peels. 35681381 1 33 theme peels 266:270 arg1 polysaccharide 272:285 Cucumis metuliferus peels polysaccharide 246:285 Cucumis metuliferus peels polysaccharide (CMPP) 246:292 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 1 33 theme peels 266:270 arg1 peels 232:236 kiwano (Cucumis metuliferus) peels 203:236 kiwano (Cucumis metuliferus) peels 203:236 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 1 33 theme peels 266:270 arg1 CMPP 288:291 CMPP 288:291 CMPP 288:291 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 10 34 theme scientific 1561:1570 arg1 basis 1572:1576 the scientific basis 1557:1576 the scientific basis of developing kiwano peels as beneficial to human health 1557:1633 This study could be the scientific basis of developing kiwano peels as beneficial to human health. 35681381 10 34 theme scientific 1561:1570 arg1 study 1542:1546 This study 1537:1546 This study 1537:1546 This study could be the scientific basis of developing kiwano peels as beneficial to human health. 35681381 2 35 theme chemical 410:417 arg1 methods 419:425 chemical methods 410:425 chemical methods 410:425 The composition of polysaccharides was analyzed by chemical methods. 35681381 5 36 theme factor 837:842 arg1 release 792:798 the release 788:798 the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) 788:877 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 6 37 theme Bacteroides 1021:1031 arg1 growth 998:1003 the growth 994:1003 the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia 994:1081 In addition, CMPP had an impact on the composition of the gut bacteria, increasing the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia. 35681381 8 38 theme 0.45 1355:1358 arg1 ± 1353:1353 ± 1353:1353 ± 1353:1353 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 7 39 dep especially 1166:1175 arg1 p 1178:1178 p 1178:1178 p < 0.05 1178:1188 During the intake period, acetic, butyric and propionic acids were all increased, especially (p < 0.05) in the descending colon. 35681381 8 40 theme 0.50 1271:1274 arg1 ± 1269:1269 ± 1269:1269 ± 1269:1269 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 7 41 dep p 1178:1178 arg1 < 1180:1182 < 1180:1182 p < 0.05 1178:1188 During the intake period, acetic, butyric and propionic acids were all increased, especially (p < 0.05) in the descending colon. 35681381 7 41 dep p 1178:1178 arg1 0.05 1185:1188 0.05 1185:1188 0.05 1185:1188 During the intake period, acetic, butyric and propionic acids were all increased, especially (p < 0.05) in the descending colon. 35681381 0 42 theme Microbiota 31:40 arg1 Modulation 42:51 Immunological Activity and Gut Microbiota Modulation 0:51 Modulation 42:51 Immunological Activity and Gut Microbiota Modulation of Pectin from Kiwano (Cucumis metuliferus) Peels. 35681381 10 43 theme human 1622:1626 arg1 health 1628:1633 human health 1622:1633 human health 1622:1633 This study could be the scientific basis of developing kiwano peels as beneficial to human health. 35681381 4 44 theme glucuronic 587:596 arg1 acid 598:601 glucuronic acid 587:601 glucuronic acid 587:601 The result showed that CMPP mainly consists of glucuronic acid, arabinose, galactose and rhamnose. 35681381 5 45 theme nitric 803:808 arg1 NO 817:818 NO 817:818 NO 817:818 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 5 45 theme nitric 803:808 arg1 oxide 810:814 nitric oxide 803:814 nitric oxide (NO) 803:819 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 1 46 theme kiwano 203:208 arg1 polysaccharide 272:285 Cucumis metuliferus peels polysaccharide 246:285 Cucumis metuliferus peels polysaccharide (CMPP) 246:292 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 1 46 theme kiwano 203:208 arg1 peels 232:236 kiwano (Cucumis metuliferus) peels 203:236 kiwano (Cucumis metuliferus) peels 203:236 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 0 47 theme Pectin 56:61 arg1 Modulation 42:51 Immunological Activity and Gut Microbiota Modulation 0:51 Modulation 42:51 Immunological Activity and Gut Microbiota Modulation of Pectin from Kiwano (Cucumis metuliferus) Peels. 35681381 0 47 theme Pectin 56:61 arg1 Activity 14:21 Immunological Activity and Gut Microbiota Modulation 0:51 Activity 14:21 Immunological Activity and Gut Microbiota Modulation of Pectin from Kiwano (Cucumis metuliferus) Peels. 35681381 8 48 theme 13.62 1347:1351 arg1 ± 1353:1353 ± 1353:1353 ± 1353:1353 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 49 theme ammonia 1240:1246 arg1 concentration 1248:1260 ammonia concentration 1240:1260 ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) 1240:1400 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 6 50 theme bacteria 973:980 arg1 composition 950:960 the composition 946:960 the composition of the gut bacteria 946:980 In addition, CMPP had an impact on the composition of the gut bacteria, increasing the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia. 35681381 6 51 theme Feacalibacterium 1051:1066 arg1 growth 998:1003 the growth 994:1003 the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia 994:1081 In addition, CMPP had an impact on the composition of the gut bacteria, increasing the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia. 35681381 8 52 from mM 1316:1317 arg1 colon 1296:1300 the ascending colon 1282:1300 the ascending colon 1282:1300 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 52 from mM 1316:1317 arg1 colon 1337:1341 the transverse colon 1322:1341 the transverse colon 1322:1341 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 52 from mM 1316:1317 arg1 colon 1381:1385 the descending colon 1366:1385 the descending colon 1366:1385 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 53 theme 10.17 1263:1267 arg1 ± 1269:1269 ± 1269:1269 ± 1269:1269 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 8 54 theme descending 1370:1379 arg1 colon 1381:1385 the descending colon 1366:1385 the descending colon 1366:1385 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 0 55 from Peels 97:101 arg1 Modulation 42:51 Immunological Activity and Gut Microbiota Modulation 0:51 Modulation 42:51 Immunological Activity and Gut Microbiota Modulation of Pectin from Kiwano (Cucumis metuliferus) Peels. 35681381 0 55 from Peels 97:101 arg1 Activity 14:21 Immunological Activity and Gut Microbiota Modulation 0:51 Activity 14:21 Immunological Activity and Gut Microbiota Modulation of Pectin from Kiwano (Cucumis metuliferus) Peels. 35681381 3 56 dep macrophages 437:447 arg1 cells 449:453 cells 449:453 cells 449:453 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 3 57 theme microbiota 463:472 arg1 dynamics 474:481 the microbiota dynamics simulator (BFBL gut model) 459:508 the microbiota dynamics simulator (BFBL gut model) 459:508 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 5 58 theme RAW264.7 659:666 arg1 cells 668:672 RAW264.7 cells 659:672 RAW264.7 cells 659:672 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 8 59 theme 13.21 1303:1307 arg1 ± 1309:1309 ± 1309:1309 ± 1309:1309 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 7 60 theme descending 1198:1207 arg1 colon 1209:1213 the descending colon 1194:1213 the descending colon 1194:1213 During the intake period, acetic, butyric and propionic acids were all increased, especially (p < 0.05) in the descending colon. 35681381 3 61 dep in 524:525 arg1 vitro 527:531 vitro 527:531 vitro 527:531 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 7 62 theme propionic 1130:1138 arg1 acids 1140:1144 acetic, butyric and propionic acids 1110:1144 acetic, butyric and propionic acids 1110:1144 During the intake period, acetic, butyric and propionic acids were all increased, especially (p < 0.05) in the descending colon. 35681381 5 63 theme immune-enhancing 719:734 arg1 activity 736:743 immune-enhancing activity 719:743 immune-enhancing activity 719:743 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 2 64 theme polysaccharides 378:392 arg1 composition 363:373 The composition 359:373 The composition of polysaccharides 359:392 The composition of polysaccharides was analyzed by chemical methods. 35681381 6 65 theme Roseburia 1073:1081 arg1 growth 998:1003 the growth 994:1003 the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia 994:1081 In addition, CMPP had an impact on the composition of the gut bacteria, increasing the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia. 35681381 7 66 theme butyric 1118:1124 arg1 acids 1140:1144 acetic, butyric and propionic acids 1110:1144 acetic, butyric and propionic acids 1110:1144 During the intake period, acetic, butyric and propionic acids were all increased, especially (p < 0.05) in the descending colon. 35681381 3 67 dep dynamics 474:481 arg1 simulator 483:491 simulator 483:491 the microbiota dynamics simulator (BFBL gut model) 459:508 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 3 67 dep dynamics 474:481 arg1 model 503:507 BFBL gut model 494:507 BFBL gut model 494:507 RAW264.7 macrophages cells and the microbiota dynamics simulator (BFBL gut model) were used for in vitro study. 35681381 9 68 theme modulation 1525:1534 arg1 function 1498:1505 function 1498:1505 function 1498:1505 In summary, CMPP can be considered as a pectin, showed immunological activity and function of gut microbiota modulation. 35681381 9 68 theme modulation 1525:1534 arg1 activity 1485:1492 immunological activity 1471:1492 immunological activity 1471:1492 In summary, CMPP can be considered as a pectin, showed immunological activity and function of gut microbiota modulation. 35681381 8 69 theme 1.54 1311:1314 arg1 ± 1309:1309 ± 1309:1309 ± 1309:1309 Moreover, a decrease in ammonia concentration (10.17 ± 0.50 mM in the ascending colon, 13.21 ± 1.54 mM in the transverse colon and 13.62 ± 0.45 mM in the descending colon, respectively) was observed. 35681381 5 70 theme μg/mL 904:908 arg1 concentration 884:896 a concentration 882:896 a concentration of 50 μg/mL 882:908 By intervening with RAW264.7 cells, CMPP promoted cell proliferation and showed immune-enhancing activity, which significantly (p < 0.05) induced the release of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) at a concentration of 50 μg/mL. 35681381 1 71 from kiwano 159:164 arg1 recycling 123:131 the recycling 119:131 the recycling of fruit by-products from kiwano 119:164 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 1 72 theme fruit 136:140 arg1 by-products 142:152 fruit by-products 136:152 fruit by-products 136:152 For developing the recycling of fruit by-products from kiwano, a polysaccharide was extracted from kiwano (Cucumis metuliferus) peels, namely Cucumis metuliferus peels polysaccharide (CMPP), with the aim of investigating the potential beneficial effects. 35681381 7 73 theme acetic 1110:1115 arg1 acids 1140:1144 acetic, butyric and propionic acids 1110:1144 acetic, butyric and propionic acids 1110:1144 During the intake period, acetic, butyric and propionic acids were all increased, especially (p < 0.05) in the descending colon. 35681381 6 74 from impact 936:941 arg1 composition 950:960 the composition 946:960 the composition of the gut bacteria 946:980 In addition, CMPP had an impact on the composition of the gut bacteria, increasing the growth of Akkermansia, Bacteroides, Bifidobacterium, Feacalibacterium, and Roseburia. 36840432 0 0 theme silver 69:74 arg1 carp 76:79 silver carp surimi 69:86 silver carp surimi 69:86 Effect of oat β-glucan on gel properties and protein conformation of silver carp surimi. 36840432 9 1 theme large 1204:1208 arg1 cavities 1223:1230 large and numerous cavities 1204:1230 large and numerous cavities 1204:1230 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 7 2 theme denser 887:892 arg1 structure 902:910 a denser network structure 885:910 a denser network structure with smaller and more uniform voids 885:946 Consequently, surimi/OG gels displayed a denser network structure with smaller and more uniform voids. 36840432 8 3 theme water-holding 1050:1062 arg1 capacity 1064:1071 the water-holding capacity 1046:1071 the water-holding capacity (WHC) 1046:1077 Furthermore, partial free water in the gel network was converted into immobile water, increasing the water-holding capacity (WHC). 36840432 8 3 theme water-holding 1050:1062 arg1 WHC 1074:1076 WHC 1074:1076 WHC 1074:1076 Furthermore, partial free water in the gel network was converted into immobile water, increasing the water-holding capacity (WHC). 36840432 10 4 theme composite 1263:1271 arg1 gels 1273:1276 composite gels 1263:1276 composite gels 1263:1276 In addition, the whiteness of composite gels decreased with the content of OG. 36840432 9 5 theme numerous 1214:1221 arg1 cavities 1223:1230 large and numerous cavities 1204:1230 large and numerous cavities 1204:1230 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 4 6 theme carp 460:463 arg1 gels 472:475 silver carp surimi gels 453:475 silver carp surimi gels 453:475 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 11 7 theme OG 1344:1345 arg1 addition 1327:1334 The addition 1323:1334 The addition of 1.0% OG 1323:1345 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 0 8 from Effect 0:5 arg1 properties 30:39 gel properties 26:39 gel properties 26:39 Effect of oat β-glucan on gel properties and protein conformation of silver carp surimi. 36840432 0 8 from Effect 0:5 arg1 conformation 53:64 protein conformation 45:64 protein conformation of silver carp surimi 45:86 Effect of oat β-glucan on gel properties and protein conformation of silver carp surimi. 36840432 11 9 theme silver 1397:1402 arg1 carp 1404:1407 silver carp surimi 1397:1414 silver carp surimi 1397:1414 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 4 10 from effect 353:358 arg1 conformation 417:428 protein conformation 409:428 protein conformation 409:428 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 10 from effect 353:358 arg1 microstructures 434:448 microstructures 434:448 microstructures of silver carp surimi gels 434:475 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 10 from effect 353:358 arg1 levels 379:384 different levels 369:384 different levels 369:384 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 10 from effect 353:358 arg1 properties 397:406 gelling properties 389:406 gelling properties 389:406 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 9 11 theme looser 1158:1163 arg1 structure 1189:1197 a looser and more uneven network structure 1156:1197 a looser and more uneven network structure with large and numerous cavities 1156:1230 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 0 12 theme carp 76:79 arg1 properties 30:39 gel properties 26:39 gel properties 26:39 Effect of oat β-glucan on gel properties and protein conformation of silver carp surimi. 36840432 0 12 theme carp 76:79 arg1 conformation 53:64 protein conformation 45:64 protein conformation of silver carp surimi 45:86 Effect of oat β-glucan on gel properties and protein conformation of silver carp surimi. 36840432 4 13 theme protein 409:415 arg1 conformation 417:428 protein conformation 409:428 protein conformation 409:428 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 13 theme protein 409:415 arg1 properties 397:406 gelling properties 389:406 gelling properties 389:406 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 11 14 theme gelation 1373:1380 arg1 performance 1382:1392 the gelation performance 1369:1392 the gelation performance of silver carp surimi 1369:1414 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 9 15 from increase 1099:1106 arg1 concentration 1118:1130 the OG concentration 1111:1130 the OG concentration (1.0-2.0%) 1111:1141 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 9 15 from increase 1099:1106 arg1 % 1140:1140 1.0-2.0% 1133:1140 1.0-2.0% 1133:1140 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 11 16 theme functional 1492:1501 arg1 products 1510:1517 functional surimi products 1492:1517 functional surimi products 1492:1517 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 11 17 theme products 1510:1517 arg1 exploitation 1460:1471 exploitation 1460:1471 exploitation 1460:1471 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 11 17 theme products 1510:1517 arg1 manufacture 1477:1487 manufacture 1477:1487 manufacture 1477:1487 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 6 18 theme conformational 780:793 arg1 transformation 795:808 the conformational transformation 776:808 the conformational transformation from α-helix to β-sheet and β-turn 776:843 Moreover, the incorporation of OG (0-1.0%) facilitated the unfolding of proteins, resulting in the conformational transformation from α-helix to β-sheet and β-turn. 36840432 8 19 theme partial 962:968 arg1 water 975:979 partial free water 962:979 partial free water in the gel network 962:998 Furthermore, partial free water in the gel network was converted into immobile water, increasing the water-holding capacity (WHC). 36840432 5 20 from increase 507:514 arg1 % 547:547 0 to 1.0% 539:547 0 to 1.0% 539:547 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 5 20 from increase 507:514 arg1 content 526:532 the OG content 519:532 the OG content from 0 to 1.0% 519:547 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 1 21 used used 136:139 arg2 additives 144:152 additives 144:152 additives 144:152 BACKGROUND Polysaccharides are the most widely used as additives to enhance the quality of surimi gels. 36840432 1 21 used used 136:139 arg2 Polysaccharides 100:114 BACKGROUND Polysaccharides 89:114 BACKGROUND Polysaccharides 89:114 BACKGROUND Polysaccharides are the most widely used as additives to enhance the quality of surimi gels. 36840432 9 22 theme uneven 1174:1179 arg1 structure 1189:1197 a looser and more uneven network structure 1156:1197 a looser and more uneven network structure with large and numerous cavities 1156:1230 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 9 23 theme further 1091:1097 arg1 increase 1099:1106 a further increase 1089:1106 a further increase 1089:1106 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 9 24 theme network 1181:1187 arg1 structure 1189:1197 a looser and more uneven network structure 1156:1197 a looser and more uneven network structure with large and numerous cavities 1156:1230 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 6 25 from α-helix 815:821 arg1 transformation 795:808 the conformational transformation 776:808 the conformational transformation from α-helix to β-sheet and β-turn 776:843 Moreover, the incorporation of OG (0-1.0%) facilitated the unfolding of proteins, resulting in the conformational transformation from α-helix to β-sheet and β-turn. 36840432 2 26 theme gelation 264:271 arg1 characteristics 273:287 the gelation characteristics 260:287 the gelation characteristics of surimi 260:297 Oat β-glucan (OG), a functional polysaccharide, is known to affect the gelation characteristics of surimi. 36840432 11 27 theme theoretical 1429:1439 arg1 foundation 1441:1450 a theoretical foundation 1427:1450 a theoretical foundation for the exploitation and manufacture of functional surimi products 1427:1517 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 8 28 theme free 970:973 arg1 water 975:979 partial free water 962:979 partial free water in the gel network 962:998 Furthermore, partial free water in the gel network was converted into immobile water, increasing the water-holding capacity (WHC). 36840432 5 29 theme OG 523:524 arg1 content 526:532 the OG content 519:532 the OG content from 0 to 1.0% 519:547 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 11 30 theme carp 1404:1407 arg1 performance 1382:1392 the gelation performance 1369:1392 the gelation performance of silver carp surimi 1369:1414 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 0 31 theme β-glucan 14:21 arg1 Effect 0:5 Effect 0:5 Effect of oat β-glucan on gel properties and protein conformation of silver carp surimi. 0:87 Effect of oat β-glucan on gel properties and protein conformation of silver carp surimi. 36840432 9 32 with structure 1189:1197 arg1 cavities 1223:1230 large and numerous cavities 1204:1230 large and numerous cavities 1204:1230 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 6 33 theme OG 712:713 arg1 incorporation 695:707 the incorporation 691:707 the incorporation of OG (0-1.0%) 691:722 Moreover, the incorporation of OG (0-1.0%) facilitated the unfolding of proteins, resulting in the conformational transformation from α-helix to β-sheet and β-turn. 36840432 10 34 theme OG 1308:1309 arg1 content 1297:1303 the content 1293:1303 the content of OG 1293:1309 In addition, the whiteness of composite gels decreased with the content of OG. 36840432 0 35 theme oat 10:12 arg1 β-glucan 14:21 oat β-glucan 10:21 oat β-glucan 10:21 Effect of oat β-glucan on gel properties and protein conformation of silver carp surimi. 36840432 5 36 from % 547:547 arg1 content 526:532 the OG content 519:532 the OG content from 0 to 1.0% 519:547 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 5 36 from % 547:547 arg1 increase 507:514 An increase 504:514 An increase in the OG content from 0 to 1.0% 504:547 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 5 37 theme storage 631:637 arg1 modulus 639:645 storage modulus 631:645 storage modulus 631:645 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 1 38 theme BACKGROUND 89:98 arg1 Polysaccharides 100:114 BACKGROUND Polysaccharides 89:114 BACKGROUND Polysaccharides 89:114 BACKGROUND Polysaccharides are the most widely used as additives to enhance the quality of surimi gels. 36840432 1 38 theme BACKGROUND 89:98 arg1 additives 144:152 additives 144:152 additives 144:152 BACKGROUND Polysaccharides are the most widely used as additives to enhance the quality of surimi gels. 36840432 7 39 theme surimi/OG 860:868 arg1 gels 870:873 surimi/OG gels 860:873 surimi/OG gels 860:873 Consequently, surimi/OG gels displayed a denser network structure with smaller and more uniform voids. 36840432 1 40 theme surimi 180:185 arg1 gels 187:190 surimi gels 180:190 surimi gels 180:190 BACKGROUND Polysaccharides are the most widely used as additives to enhance the quality of surimi gels. 36840432 0 41 theme gel 26:28 arg1 properties 30:39 gel properties 26:39 gel properties 26:39 Effect of oat β-glucan on gel properties and protein conformation of silver carp surimi. 36840432 9 42 theme OG 1115:1116 arg1 concentration 1118:1130 the OG concentration 1111:1130 the OG concentration (1.0-2.0%) 1111:1141 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 9 42 theme OG 1115:1116 arg1 % 1140:1140 1.0-2.0% 1133:1140 1.0-2.0% 1133:1140 However, a further increase in the OG concentration (1.0-2.0%), resulted in a looser and more uneven network structure with large and numerous cavities. 36840432 1 43 theme gels 187:190 arg1 quality 169:175 the quality 165:175 the quality of surimi gels 165:190 BACKGROUND Polysaccharides are the most widely used as additives to enhance the quality of surimi gels. 36840432 8 44 theme immobile 1019:1026 arg1 water 1028:1032 immobile water 1019:1032 immobile water 1019:1032 Furthermore, partial free water in the gel network was converted into immobile water, increasing the water-holding capacity (WHC). 36840432 4 45 theme gels 472:475 arg1 conformation 417:428 protein conformation 409:428 protein conformation 409:428 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 45 theme gels 472:475 arg1 microstructures 434:448 microstructures 434:448 microstructures of silver carp surimi gels 434:475 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 45 theme gels 472:475 arg1 properties 397:406 gelling properties 389:406 gelling properties 389:406 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 46 from levels 379:384 arg1 OG 363:364 OG 363:364 OG at different levels 363:384 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 46 from levels 379:384 arg1 effect 353:358 the effect 349:358 the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels 349:475 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 6 47 theme proteins 753:760 arg1 unfolding 740:748 the unfolding 736:748 the unfolding of proteins 736:760 Moreover, the incorporation of OG (0-1.0%) facilitated the unfolding of proteins, resulting in the conformational transformation from α-helix to β-sheet and β-turn. 36840432 10 48 theme gels 1273:1276 arg1 whiteness 1250:1258 the whiteness 1246:1258 the whiteness of composite gels 1246:1276 In addition, the whiteness of composite gels decreased with the content of OG. 36840432 4 49 theme surimi 465:470 arg1 gels 472:475 silver carp surimi gels 453:475 silver carp surimi gels 453:475 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 50 theme gelling 389:395 arg1 conformation 417:428 protein conformation 409:428 protein conformation 409:428 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 50 theme gelling 389:395 arg1 microstructures 434:448 microstructures 434:448 microstructures of silver carp surimi gels 434:475 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 50 theme gelling 389:395 arg1 properties 397:406 gelling properties 389:406 gelling properties 389:406 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 7 51 theme uniform 934:940 arg1 voids 942:946 smaller and more uniform voids 917:946 smaller and more uniform voids 917:946 Consequently, surimi/OG gels displayed a denser network structure with smaller and more uniform voids. 36840432 8 52 from water 975:979 arg1 network 992:998 the gel network 984:998 the gel network 984:998 Furthermore, partial free water in the gel network was converted into immobile water, increasing the water-holding capacity (WHC). 36840432 4 53 theme silver 453:458 arg1 carp 460:463 silver carp 453:463 silver carp surimi gels 453:475 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 4 54 theme OG 363:364 arg1 effect 353:358 the effect 349:358 the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels 349:475 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 2 55 theme Oat 193:195 arg1 polysaccharide 225:238 a functional polysaccharide 212:238 a functional polysaccharide 212:238 Oat β-glucan (OG), a functional polysaccharide, is known to affect the gelation characteristics of surimi. 36840432 2 55 theme Oat 193:195 arg1 OG 207:208 OG 207:208 OG 207:208 Oat β-glucan (OG), a functional polysaccharide, is known to affect the gelation characteristics of surimi. 36840432 2 55 theme Oat 193:195 arg1 β-glucan 197:204 Oat β-glucan 193:204 Oat β-glucan (OG) 193:209 Oat β-glucan (OG), a functional polysaccharide, is known to affect the gelation characteristics of surimi. 36840432 2 56 theme surimi 292:297 arg1 characteristics 273:287 the gelation characteristics 260:287 the gelation characteristics of surimi 260:297 Oat β-glucan (OG), a functional polysaccharide, is known to affect the gelation characteristics of surimi. 36840432 11 57 theme 1.0 1339:1341 arg1 % 1342:1342 % 1342:1342 % 1342:1342 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 5 58 theme puncture 610:617 arg1 properties 619:628 puncture properties 610:628 puncture properties 610:628 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 2 59 theme functional 214:223 arg1 polysaccharide 225:238 a functional polysaccharide 212:238 a functional polysaccharide 212:238 Oat β-glucan (OG), a functional polysaccharide, is known to affect the gelation characteristics of surimi. 36840432 2 59 theme functional 214:223 arg1 β-glucan 197:204 Oat β-glucan 193:204 Oat β-glucan (OG) 193:209 Oat β-glucan (OG), a functional polysaccharide, is known to affect the gelation characteristics of surimi. 36840432 5 60 theme gels 675:678 arg1 modulus 639:645 storage modulus 631:645 storage modulus 631:645 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 5 60 theme gels 675:678 arg1 chewiness 599:607 chewiness 599:607 chewiness 599:607 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 5 60 theme gels 675:678 arg1 properties 619:628 puncture properties 610:628 puncture properties 610:628 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 5 60 theme gels 675:678 arg1 hardness 576:583 the hardness 572:583 the hardness 572:583 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 5 60 theme gels 675:678 arg1 modulus 657:663 loss modulus 652:663 loss modulus 652:663 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 5 60 theme gels 675:678 arg1 springiness 586:596 springiness 586:596 springiness 586:596 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 5 61 dep 1.0 544:546 arg1 to 541:542 to 541:542 to 541:542 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 7 62 theme smaller 917:923 arg1 voids 942:946 smaller and more uniform voids 917:946 smaller and more uniform voids 917:946 Consequently, surimi/OG gels displayed a denser network structure with smaller and more uniform voids. 36840432 4 63 theme different 369:377 arg1 levels 379:384 different levels 369:384 different levels 369:384 Therefore, the effect of OG at different levels on gelling properties, protein conformation and microstructures of silver carp surimi gels were investigated. 36840432 7 64 theme network 894:900 arg1 structure 902:910 a denser network structure 885:910 a denser network structure with smaller and more uniform voids 885:946 Consequently, surimi/OG gels displayed a denser network structure with smaller and more uniform voids. 36840432 11 65 dep exploitation 1460:1471 arg1 the 1456:1458 the 1456:1458 the 1456:1458 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 5 66 theme surimi 668:673 arg1 gels 675:678 surimi gels 668:678 surimi gels 668:678 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36840432 11 67 theme % 1342:1342 arg1 OG 1344:1345 1.0% OG 1339:1345 1.0% OG 1339:1345 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 0 68 theme protein 45:51 arg1 conformation 53:64 protein conformation 45:64 protein conformation of silver carp surimi 45:86 Effect of oat β-glucan on gel properties and protein conformation of silver carp surimi. 36840432 11 69 theme surimi 1503:1508 arg1 products 1510:1517 functional surimi products 1492:1517 functional surimi products 1492:1517 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 7 70 with structure 902:910 arg1 voids 942:946 smaller and more uniform voids 917:946 smaller and more uniform voids 917:946 Consequently, surimi/OG gels displayed a denser network structure with smaller and more uniform voids. 36840432 11 71 dep CONCLUSION 1312:1321 arg1 improved 1360:1367 improved 1360:1367 improved 1360:1367 CONCLUSION The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. 36840432 8 72 theme gel 988:990 arg1 network 992:998 the gel network 984:998 the gel network 984:998 Furthermore, partial free water in the gel network was converted into immobile water, increasing the water-holding capacity (WHC). 36840432 5 73 theme loss 652:655 arg1 modulus 657:663 loss modulus 652:663 loss modulus 652:663 RESULTS An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. 36743002 6 0 theme sample 968:973 arg1 preparation 975:985 sample preparation 968:985 this sample preparation strategy 963:994 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 1 theme unique 1181:1186 arg1 peptides 1188:1195 156 unique peptides 1177:1195 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample 1177:1383 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 2 2 theme subsequent 388:397 arg1 analysis 417:424 subsequent mass spectrometry analysis 388:424 subsequent mass spectrometry analysis 388:424 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 6 3 theme control 1370:1376 arg1 sample 1378:1383 a control sample 1368:1383 a control sample 1368:1383 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 2 4 theme N-glycosidase 338:350 arg1 F 352:352 N-glycosidase F 338:352 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis 289:424 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 2 4 theme N-glycosidase 338:350 arg1 F 362:362 PNGase F 355:362 PNGase F 355:362 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 6 5 theme deamidation 1273:1283 arg1 characteristic 1298:1311 the deamidation modification characteristic 1269:1311 the deamidation modification characteristic of PNGase F 1269:1323 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 6 from samples 1115:1121 arg1 identification 1045:1058 improved identification 1036:1058 improved identification of potential N-glycosylated peptides in deglycosylated samples 1036:1121 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 3 7 dep way 610:612 arg1 integrate 617:625 integrate 617:625 to integrate deglycosylation with bottom-up proteomics 614:667 An efficient way to integrate deglycosylation with bottom-up proteomics would be a valuable contribution to the glycoproteomics field. 36743002 7 8 theme potential 1511:1519 arg1 glycoproteins 1521:1533 both known and potential glycoproteins 1496:1533 both known and potential glycoproteins 1496:1533 We expect that this rapid sample preparation strategy will assist in the identification and quantification of both known and potential glycoproteins. 36743002 6 9 theme peptide 1345:1351 arg1 intensity 1353:1361 peptide intensity 1345:1361 peptide intensity 1345:1361 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 2 10 theme sample 569:574 arg1 preparation 576:586 an already lengthy sample preparation 550:586 an already lengthy sample preparation process 550:594 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 7 11 theme known 1501:1505 arg1 glycoproteins 1521:1533 both known and potential glycoproteins 1496:1533 both known and potential glycoproteins 1496:1533 We expect that this rapid sample preparation strategy will assist in the identification and quantification of both known and potential glycoproteins. 36743002 6 12 theme serum 1007:1011 arg1 sample 1013:1018 a human serum sample 999:1018 a human serum sample 999:1018 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 7 13 theme preparation 1419:1429 arg1 strategy 1431:1438 this rapid sample preparation strategy 1401:1438 this rapid sample preparation strategy 1401:1438 We expect that this rapid sample preparation strategy will assist in the identification and quantification of both known and potential glycoproteins. 36743002 8 14 with available 1545:1553 arg1 PXD037921 1595:1603 the identifier PXD037921 1580:1603 the identifier PXD037921 1580:1603 Data are available via ProteomeXchange with the identifier PXD037921. 36743002 1 15 theme bottom-up 255:263 arg1 experiments 276:286 traditional bottom-up proteomics experiments 243:286 traditional bottom-up proteomics experiments 243:286 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 8 16 theme identifier 1584:1593 arg1 PXD037921 1595:1603 the identifier PXD037921 1580:1603 the identifier PXD037921 1580:1603 Data are available via ProteomeXchange with the identifier PXD037921. 36743002 4 17 theme proteomics 755:764 arg1 workflow 766:773 a proteomics workflow 753:773 a proteomics workflow in which deglycosylation and proteolytic digestion of samples occur simultaneously using suspension trapping (S-Trap) 753:891 Here, we demonstrate a proteomics workflow in which deglycosylation and proteolytic digestion of samples occur simultaneously using suspension trapping (S-Trap). 36743002 2 18 theme proteins 318:325 arg1 deglycosylation 299:313 Enzymatic deglycosylation 289:313 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis 289:424 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 1 19 theme important 155:163 arg1 modification 184:195 an important post-translational modification 152:195 an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments 152:286 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 1 19 theme important 155:163 arg1 glycosylation 135:147 N-linked glycosylation 126:147 N-linked glycosylation 126:147 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 1 19 theme important 155:163 arg1 difficult 205:213 difficult 205:213 difficult 205:213 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 6 20 theme peptides 1088:1095 arg1 identification 1045:1058 improved identification 1036:1058 improved identification of potential N-glycosylated peptides in deglycosylated samples 1036:1121 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 21 theme PNGase 1316:1321 arg1 F 1323:1323 PNGase F 1316:1323 PNGase F 1316:1323 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 22 from increase 1333:1340 arg1 intensity 1353:1361 peptide intensity 1345:1361 peptide intensity 1345:1361 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 5 23 theme digestion 933:941 arg1 protocols 943:951 standard digestion protocols 924:951 standard digestion protocols 924:951 This approach adds no time to standard digestion protocols. 36743002 6 24 theme potential 1063:1071 arg1 peptides 1088:1095 potential N-glycosylated peptides 1063:1095 potential N-glycosylated peptides in deglycosylated samples 1063:1121 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 0 25 theme Efficient 83:91 arg1 Generation 114:123 Efficient Glycosite Hypothesis Generation 83:123 Efficient Glycosite Hypothesis Generation 83:123 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 2 26 link N-linked 472:479 arg1 glycopeptides 481:493 various N-linked glycopeptides 464:493 various N-linked glycopeptides 464:493 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 4 27 theme proteolytic 804:814 arg1 digestion 816:824 proteolytic digestion 804:824 proteolytic digestion of samples 804:835 Here, we demonstrate a proteomics workflow in which deglycosylation and proteolytic digestion of samples occur simultaneously using suspension trapping (S-Trap). 36743002 0 28 theme Hypothesis 103:112 arg1 Generation 114:123 Efficient Glycosite Hypothesis Generation 83:123 Efficient Glycosite Hypothesis Generation 83:123 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 6 29 gly N-glycosylation 1214:1228 arg2 motif 1230:1234 the N-glycosylation motif 1210:1234 the N-glycosylation motif (asparagine-X-serine/threonine) 1210:1266 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 29 gly N-glycosylation 1214:1228 arg2 asparagine-X-serine/threonine 1237:1265 asparagine-X-serine/threonine 1237:1265 asparagine-X-serine/threonine 1237:1265 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 4 30 gly deglycosylation 784:798 arg2 workflow 766:773 a proteomics workflow 753:773 a proteomics workflow in which deglycosylation and proteolytic digestion of samples occur simultaneously using suspension trapping (S-Trap) 753:891 Here, we demonstrate a proteomics workflow in which deglycosylation and proteolytic digestion of samples occur simultaneously using suspension trapping (S-Trap). 36743002 4 30 gly deglycosylation 784:798 arg1 samples 829:835 samples 829:835 samples 829:835 Here, we demonstrate a proteomics workflow in which deglycosylation and proteolytic digestion of samples occur simultaneously using suspension trapping (S-Trap). 36743002 0 31 theme Simultaneous 0:11 arg1 N-Deglycosylation 13:29 Simultaneous N-Deglycosylation 0:29 Simultaneous N-Deglycosylation 0:29 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 6 32 theme non-deglycosylated 1137:1154 arg1 samples 1156:1162 non-deglycosylated samples 1137:1162 non-deglycosylated samples 1137:1162 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 2 33 theme glycopeptides 481:493 arg1 coverage 452:459 coverage 452:459 coverage of various N-linked glycopeptides 452:493 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 2 34 theme various 464:470 arg1 glycopeptides 481:493 various N-linked glycopeptides 464:493 various N-linked glycopeptides 464:493 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 1 35 theme N-linked 126:133 arg1 modification 184:195 an important post-translational modification 152:195 an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments 152:286 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 1 35 theme N-linked 126:133 arg1 glycosylation 135:147 N-linked glycosylation 126:147 N-linked glycosylation 126:147 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 1 35 theme N-linked 126:133 arg1 difficult 205:213 difficult 205:213 difficult 205:213 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 7 36 theme rapid 1406:1410 arg1 preparation 1419:1429 this rapid sample preparation 1401:1429 this rapid sample preparation strategy 1401:1438 We expect that this rapid sample preparation strategy will assist in the identification and quantification of both known and potential glycoproteins. 36743002 6 37 gly deglycosylated 1100:1113 arg1 samples 1115:1121 deglycosylated samples 1100:1121 deglycosylated samples 1100:1121 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 3 38 theme valuable 680:687 arg1 way 610:612 An efficient way 597:612 An efficient way to integrate deglycosylation with bottom-up proteomics 597:667 An efficient way to integrate deglycosylation with bottom-up proteomics would be a valuable contribution to the glycoproteomics field. 36743002 3 38 theme valuable 680:687 arg1 contribution 689:700 a valuable contribution 678:700 a valuable contribution to the glycoproteomics field 678:729 An efficient way to integrate deglycosylation with bottom-up proteomics would be a valuable contribution to the glycoproteomics field. 36743002 0 39 gly N-Deglycosylation 13:29 arg1 S-Traps 67:73 S-Traps 67:73 S-Traps 67:73 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 0 39 gly N-Deglycosylation 13:29 arg1 Samples 56:62 Complex Samples 48:62 Complex Samples 48:62 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 6 40 theme deglycosylated 1100:1113 arg1 samples 1115:1121 deglycosylated samples 1100:1121 deglycosylated samples 1100:1121 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 0 41 theme Samples 56:62 arg1 Digestion 35:43 Digestion 35:43 Digestion 35:43 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 0 41 theme Samples 56:62 arg1 N-Deglycosylation 13:29 Simultaneous N-Deglycosylation 0:29 Simultaneous N-Deglycosylation 0:29 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 6 42 theme N-glycosylation 1214:1228 arg1 asparagine-X-serine/threonine 1237:1265 asparagine-X-serine/threonine 1237:1265 asparagine-X-serine/threonine 1237:1265 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 42 theme N-glycosylation 1214:1228 arg1 motif 1230:1234 the N-glycosylation motif 1210:1234 the N-glycosylation motif (asparagine-X-serine/threonine) 1210:1266 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 43 gly non-deglycosylated 1137:1154 arg1 samples 1156:1162 non-deglycosylated samples 1137:1162 non-deglycosylated samples 1137:1162 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 3 44 theme glycoproteomics 709:723 arg1 field 725:729 the glycoproteomics field 705:729 the glycoproteomics field 705:729 An efficient way to integrate deglycosylation with bottom-up proteomics would be a valuable contribution to the glycoproteomics field. 36743002 1 45 theme proteomics 265:274 arg1 experiments 276:286 traditional bottom-up proteomics experiments 243:286 traditional bottom-up proteomics experiments 243:286 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 6 46 theme preparation 975:985 arg1 strategy 987:994 this sample preparation strategy 963:994 this sample preparation strategy 963:994 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 2 47 gly glycopeptides 481:493 arg2 glycopeptides 481:493 various N-linked glycopeptides 464:493 various N-linked glycopeptides 464:493 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 6 48 gly N-glycosylated 1073:1086 arg1 peptides 1088:1095 potential N-glycosylated peptides 1063:1095 potential N-glycosylated peptides in deglycosylated samples 1063:1121 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 2 49 theme mass 399:402 arg1 analysis 417:424 subsequent mass spectrometry analysis 388:424 subsequent mass spectrometry analysis 388:424 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 6 50 theme modification 1285:1296 arg1 characteristic 1298:1311 the deamidation modification characteristic 1269:1311 the deamidation modification characteristic of PNGase F 1269:1323 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 2 51 dep deglycosylation 299:313 arg1 F 352:352 N-glycosidase F 338:352 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis 289:424 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 2 51 dep deglycosylation 299:313 arg1 F 362:362 PNGase F 355:362 PNGase F 355:362 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 7 52 theme glycoproteins 1521:1533 arg1 quantification 1478:1491 quantification 1478:1491 quantification 1478:1491 We expect that this rapid sample preparation strategy will assist in the identification and quantification of both known and potential glycoproteins. 36743002 7 52 theme glycoproteins 1521:1533 arg1 identification 1459:1472 identification 1459:1472 identification 1459:1472 We expect that this rapid sample preparation strategy will assist in the identification and quantification of both known and potential glycoproteins. 36743002 2 53 gly deglycosylation 299:313 arg1 proteins 318:325 proteins 318:325 proteins 318:325 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 2 54 theme PNGase 355:360 arg1 F 352:352 N-glycosidase F 338:352 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis 289:424 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 2 54 theme PNGase 355:360 arg1 F 362:362 PNGase F 355:362 PNGase F 355:362 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 2 55 theme lengthy 561:567 arg1 preparation 576:586 an already lengthy sample preparation 550:586 an already lengthy sample preparation process 550:594 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 6 56 contain contain 1202:1208 arg1 peptides 1188:1195 156 unique peptides 1177:1195 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample 1177:1383 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 56 contain contain 1202:1208 arg2 motif 1230:1234 the N-glycosylation motif 1210:1234 the N-glycosylation motif (asparagine-X-serine/threonine) 1210:1266 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 56 contain contain 1202:1208 arg2 increase 1333:1340 an increase 1330:1340 an increase in peptide intensity over a control sample 1330:1383 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 56 contain contain 1202:1208 arg2 characteristic 1298:1311 the deamidation modification characteristic 1269:1311 the deamidation modification characteristic of PNGase F 1269:1323 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 56 contain contain 1202:1208 arg2 asparagine-X-serine/threonine 1237:1265 asparagine-X-serine/threonine 1237:1265 asparagine-X-serine/threonine 1237:1265 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 1 57 theme post-translational 165:182 arg1 modification 184:195 an important post-translational modification 152:195 an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments 152:286 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 1 57 theme post-translational 165:182 arg1 glycosylation 135:147 N-linked glycosylation 126:147 N-linked glycosylation 126:147 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 1 57 theme post-translational 165:182 arg1 difficult 205:213 difficult 205:213 difficult 205:213 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 2 58 theme Enzymatic 289:297 arg1 deglycosylation 299:313 Enzymatic deglycosylation 289:313 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis 289:424 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 1 59 theme traditional 243:253 arg1 experiments 276:286 traditional bottom-up proteomics experiments 243:286 traditional bottom-up proteomics experiments 243:286 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 6 60 theme human 1001:1005 arg1 sample 1013:1018 a human serum sample 999:1018 a human serum sample 999:1018 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 3 61 theme efficient 600:608 arg1 way 610:612 An efficient way 597:612 An efficient way to integrate deglycosylation with bottom-up proteomics 597:667 An efficient way to integrate deglycosylation with bottom-up proteomics would be a valuable contribution to the glycoproteomics field. 36743002 3 61 theme efficient 600:608 arg1 contribution 689:700 a valuable contribution 678:700 a valuable contribution to the glycoproteomics field 678:729 An efficient way to integrate deglycosylation with bottom-up proteomics would be a valuable contribution to the glycoproteomics field. 36743002 3 62 theme bottom-up 648:656 arg1 proteomics 658:667 bottom-up proteomics 648:667 bottom-up proteomics 648:667 An efficient way to integrate deglycosylation with bottom-up proteomics would be a valuable contribution to the glycoproteomics field. 36743002 2 63 theme preparation 576:586 arg1 process 588:594 an already lengthy sample preparation process 550:594 an already lengthy sample preparation process 550:594 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 6 64 theme F 1323:1323 arg1 characteristic 1298:1311 the deamidation modification characteristic 1269:1311 the deamidation modification characteristic of PNGase F 1269:1323 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 64 theme F 1323:1323 arg1 increase 1333:1340 an increase 1330:1340 an increase in peptide intensity over a control sample 1330:1383 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 64 theme F 1323:1323 arg1 asparagine-X-serine/threonine 1237:1265 asparagine-X-serine/threonine 1237:1265 asparagine-X-serine/threonine 1237:1265 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 64 theme F 1323:1323 arg1 motif 1230:1234 the N-glycosylation motif 1210:1234 the N-glycosylation motif (asparagine-X-serine/threonine) 1210:1266 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 3 65 with deglycosylation 627:641 arg1 proteomics 658:667 bottom-up proteomics 648:667 bottom-up proteomics 648:667 An efficient way to integrate deglycosylation with bottom-up proteomics would be a valuable contribution to the glycoproteomics field. 36743002 5 66 theme standard 924:931 arg1 protocols 943:951 standard digestion protocols 924:951 standard digestion protocols 924:951 This approach adds no time to standard digestion protocols. 36743002 6 67 theme N-glycosylated 1073:1086 arg1 peptides 1088:1095 potential N-glycosylated peptides 1063:1095 potential N-glycosylated peptides in deglycosylated samples 1063:1121 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 0 68 from Digestion 35:43 arg1 S-Traps 67:73 S-Traps 67:73 S-Traps 67:73 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 0 69 theme Glycosite 93:101 arg1 Generation 114:123 Efficient Glycosite Hypothesis Generation 83:123 Efficient Glycosite Hypothesis Generation 83:123 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 2 70 theme step 522:525 arg1 inclusion 504:512 the inclusion 500:512 the inclusion of this step 500:525 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 0 71 from N-Deglycosylation 13:29 arg1 S-Traps 67:73 S-Traps 67:73 S-Traps 67:73 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 6 72 theme improved 1036:1043 arg1 identification 1045:1058 improved identification 1036:1058 improved identification of potential N-glycosylated peptides in deglycosylated samples 1036:1121 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 73 from peptides 1088:1095 arg1 samples 1115:1121 deglycosylated samples 1100:1121 deglycosylated samples 1100:1121 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 6 74 from characteristic 1298:1311 arg1 intensity 1353:1361 peptide intensity 1345:1361 peptide intensity 1345:1361 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 7 75 theme sample 1412:1417 arg1 preparation 1419:1429 this rapid sample preparation 1401:1429 this rapid sample preparation strategy 1401:1438 We expect that this rapid sample preparation strategy will assist in the identification and quantification of both known and potential glycoproteins. 36743002 6 76 from identification 1045:1058 arg1 samples 1115:1121 deglycosylated samples 1100:1121 deglycosylated samples 1100:1121 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 2 77 theme N-linked 472:479 arg1 glycopeptides 481:493 various N-linked glycopeptides 464:493 various N-linked glycopeptides 464:493 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 0 78 theme Complex 48:54 arg1 Samples 56:62 Complex Samples 48:62 Complex Samples 48:62 Simultaneous N-Deglycosylation and Digestion of Complex Samples on S-Traps Enables Efficient Glycosite Hypothesis Generation. 36743002 4 79 theme suspension 864:873 arg1 trapping 875:882 suspension trapping 864:882 suspension trapping (S-Trap) 864:891 Here, we demonstrate a proteomics workflow in which deglycosylation and proteolytic digestion of samples occur simultaneously using suspension trapping (S-Trap). 36743002 4 79 theme suspension 864:873 arg1 S-Trap 885:890 S-Trap 885:890 S-Trap 885:890 Here, we demonstrate a proteomics workflow in which deglycosylation and proteolytic digestion of samples occur simultaneously using suspension trapping (S-Trap). 36743002 6 80 from motif 1230:1234 arg1 intensity 1353:1361 peptide intensity 1345:1361 peptide intensity 1345:1361 Applying this sample preparation strategy to a human serum sample, we demonstrate improved identification of potential N-glycosylated peptides in deglycosylated samples compared with non-deglycosylated samples, identifying 156 unique peptides that contain the N-glycosylation motif (asparagine-X-serine/threonine), the deamidation modification characteristic of PNGase F, and an increase in peptide intensity over a control sample. 36743002 4 81 theme samples 829:835 arg1 deglycosylation 784:798 deglycosylation 784:798 deglycosylation 784:798 Here, we demonstrate a proteomics workflow in which deglycosylation and proteolytic digestion of samples occur simultaneously using suspension trapping (S-Trap). 36743002 4 81 theme samples 829:835 arg1 digestion 816:824 proteolytic digestion 804:824 proteolytic digestion of samples 804:835 Here, we demonstrate a proteomics workflow in which deglycosylation and proteolytic digestion of samples occur simultaneously using suspension trapping (S-Trap). 36743002 2 82 theme prior 365:369 arg1 F 352:352 N-glycosidase F 338:352 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis 289:424 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 2 82 theme prior 365:369 arg1 F 362:362 PNGase F 355:362 PNGase F 355:362 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 36743002 7 83 gly glycoproteins 1521:1533 arg1 glycoproteins 1521:1533 both known and potential glycoproteins 1496:1533 both known and potential glycoproteins 1496:1533 We expect that this rapid sample preparation strategy will assist in the identification and quantification of both known and potential glycoproteins. 36743002 7 84 dep identification 1459:1472 arg1 the 1455:1457 the 1455:1457 the 1455:1457 We expect that this rapid sample preparation strategy will assist in the identification and quantification of both known and potential glycoproteins. 36743002 1 85 link N-linked 126:133 arg1 modification 184:195 an important post-translational modification 152:195 an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments 152:286 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 1 85 link N-linked 126:133 arg1 glycosylation 135:147 N-linked glycosylation 126:147 N-linked glycosylation 126:147 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 1 85 link N-linked 126:133 arg1 difficult 205:213 difficult 205:213 difficult 205:213 N-linked glycosylation is an important post-translational modification that is difficult to identify and quantify in traditional bottom-up proteomics experiments. 36743002 2 86 theme spectrometry 404:415 arg1 analysis 417:424 subsequent mass spectrometry analysis 388:424 subsequent mass spectrometry analysis 388:424 Enzymatic deglycosylation of proteins by peptide:N-glycosidase F (PNGase F) prior to digestion and subsequent mass spectrometry analysis has been shown to improve coverage of various N-linked glycopeptides, but the inclusion of this step may add up to a day to an already lengthy sample preparation process. 35648131 5 0 located present 799:805 arg2 acids 789:793 many C-5 modified sialic acids 764:793 many C-5 modified sialic acids 764:793 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 5 0 located present 799:805 arg1 glycolipids 830:840 glycolipids 830:840 glycolipids 830:840 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 5 0 located present 799:805 arg1 glycans 819:825 N-linked glycans 810:825 N-linked glycans 810:825 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 2 1 link α2,6-linked 283:293 arg1 acids 302:306 α2,3- or α2,6-linked sialic acids 274:306 α2,3- or α2,6-linked sialic acids 274:306 A species barrier for multiple viruses is present due to α2,3- or α2,6-linked sialic acids. 35648131 9 2 link N-linked 1220:1227 arg1 glycans 1229:1235 N-linked glycans 1220:1235 N-linked glycans 1220:1235 Furthermore, the removal of N-linked glycans reduces the binding of both Neu5Gc lectins while retention of glycolipids by omitting methanol treatment of tissues increases lectin binding. 35648131 7 3 dep Suidae 1070:1075 arg1 hedgehogs 1109:1117 hedgehogs 1109:1117 hedgehogs 1109:1117 We used these lectins to map Neu5Gc content in wild Suidae, Cervidae, tigers, and European hedgehogs. 35648131 5 4 attach present 799:805 arg1 glycans 819:825 N-linked glycans 810:825 N-linked glycans 810:825 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 5 4 attach present 799:805 arg1 glycolipids 830:840 glycolipids 830:840 glycolipids 830:840 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 5 4 attach present 799:805 arg2 acids 789:793 many C-5 modified sialic acids 764:793 many C-5 modified sialic acids 764:793 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 4 5 from dogs 688:691 arg1 absent 657:662 absent 657:662 absent 657:662 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 6 6 theme detection 982:990 arg1 levels 992:997 varying detection levels 974:997 varying detection levels of Neu5Gc glycans 974:1015 Using our previously developed tissue microarray system, we investigated how 2 different lectins specific for Neu5Gc can result in varying detection levels of Neu5Gc glycans. 35648131 1 7 from variations 134:143 arg1 type 160:163 the linkage type 148:163 the linkage type 148:163 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 3 8 theme host 473:476 arg1 susceptibility 478:491 host susceptibility 473:491 host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus 473:589 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 4 9 from mammals 618:624 arg1 present 602:608 present 602:608 present 602:608 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 10 10 theme rich 1459:1462 arg1 lectins 1444:1450 multiple Neu5Gc lectins 1428:1450 multiple Neu5Gc lectins 1428:1450 These findings highlight the importance of using multiple Neu5Gc lectins as the rich variety in which Neu5Gc is displayed can hardly be detected by a single lectin. 35648131 10 10 theme rich 1459:1462 arg1 variety 1464:1470 the rich variety 1455:1470 the rich variety in which Neu5Gc is displayed can hardly be detected by a single lectin 1455:1541 These findings highlight the importance of using multiple Neu5Gc lectins as the rich variety in which Neu5Gc is displayed can hardly be detected by a single lectin. 35648131 6 11 theme microarray 881:890 arg1 system 892:897 our previously developed tissue microarray system 849:897 our previously developed tissue microarray system 849:897 Using our previously developed tissue microarray system, we investigated how 2 different lectins specific for Neu5Gc can result in varying detection levels of Neu5Gc glycans. 35648131 7 12 from content 1054:1060 arg1 Cervidae 1078:1085 Cervidae 1078:1085 Cervidae 1078:1085 We used these lectins to map Neu5Gc content in wild Suidae, Cervidae, tigers, and European hedgehogs. 35648131 7 12 from content 1054:1060 arg1 Suidae 1070:1075 Suidae 1070:1075 Suidae 1070:1075 We used these lectins to map Neu5Gc content in wild Suidae, Cervidae, tigers, and European hedgehogs. 35648131 7 12 from content 1054:1060 arg1 tigers 1088:1093 tigers 1088:1093 tigers 1088:1093 We used these lectins to map Neu5Gc content in wild Suidae, Cervidae, tigers, and European hedgehogs. 35648131 7 12 from content 1054:1060 arg1 European 1100:1107 European 1100:1107 European 1100:1107 We used these lectins to map Neu5Gc content in wild Suidae, Cervidae, tigers, and European hedgehogs. 35648131 4 13 from ferrets 675:681 arg1 absent 657:662 absent 657:662 absent 657:662 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 9 14 theme glycolipids 1299:1309 arg1 retention 1286:1294 retention 1286:1294 retention of glycolipids 1286:1309 Furthermore, the removal of N-linked glycans reduces the binding of both Neu5Gc lectins while retention of glycolipids by omitting methanol treatment of tissues increases lectin binding. 35648131 3 15 theme N-acetylneuraminic 369:386 arg1 determinant 457:467 a determinant 455:467 a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus 455:589 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 3 15 theme N-acetylneuraminic 369:386 arg1 Neu5Ac 394:399 Neu5Ac 394:399 Neu5Ac 394:399 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 3 15 theme N-acetylneuraminic 369:386 arg1 acid 388:391 N-acetylneuraminic acid 369:391 N-acetylneuraminic acid (Neu5Ac) 369:400 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 3 15 theme N-acetylneuraminic 369:386 arg1 acid 426:429 N-glycolylneuraminic acid 405:429 N-glycolylneuraminic acid (Neu5Gc) 405:438 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 6 16 theme varying 974:980 arg1 levels 992:997 varying detection levels 974:997 varying detection levels of Neu5Gc glycans 974:1015 Using our previously developed tissue microarray system, we investigated how 2 different lectins specific for Neu5Gc can result in varying detection levels of Neu5Gc glycans. 35648131 3 17 theme C-5 313:315 arg1 position 317:324 The C-5 position 309:324 The C-5 position of the sialic acid 309:343 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 2 18 theme multiple 239:246 arg1 viruses 248:254 multiple viruses 239:254 multiple viruses 239:254 A species barrier for multiple viruses is present due to α2,3- or α2,6-linked sialic acids. 35648131 4 19 from present 602:608 arg1 horses 643:648 horses 643:648 horses 643:648 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 19 from present 602:608 arg1 mammals 618:624 most mammals 613:624 most mammals such as pigs and horses 613:648 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 19 from present 602:608 arg1 pigs 634:637 pigs 634:637 pigs 634:637 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 3 20 theme acid 340:343 arg1 position 317:324 The C-5 position 309:324 The C-5 position of the sialic acid 309:343 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 9 21 theme N-linked 1220:1227 arg1 glycans 1229:1235 N-linked glycans 1220:1235 N-linked glycans 1220:1235 Furthermore, the removal of N-linked glycans reduces the binding of both Neu5Gc lectins while retention of glycolipids by omitting methanol treatment of tissues increases lectin binding. 35648131 4 22 from humans 667:672 arg1 absent 657:662 absent 657:662 absent 657:662 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 1 23 theme Sialic 75:80 arg1 receptor 102:109 a receptor 100:109 a receptor 100:109 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 1 23 theme Sialic 75:80 arg1 acids 82:86 Sialic acids 75:86 Sialic acids 75:86 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 1 23 theme Sialic 75:80 arg1 properties 205:214 the binding properties 193:214 the binding properties 193:214 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 1 24 theme linkage 152:158 arg1 type 160:163 the linkage type 148:163 the linkage type 148:163 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 0 25 theme Wild 0:3 arg1 animals 18:24 Wild and domestic animals 0:24 Wild and domestic animals 0:24 Wild and domestic animals variably display Neu5Ac and Neu5Gc sialic acids. 35648131 6 26 theme tissue 874:879 arg1 system 892:897 our previously developed tissue microarray system 849:897 our previously developed tissue microarray system 849:897 Using our previously developed tissue microarray system, we investigated how 2 different lectins specific for Neu5Gc can result in varying detection levels of Neu5Gc glycans. 35648131 2 27 theme α2,3- 274:278 arg1 acids 302:306 α2,3- or α2,6-linked sialic acids 274:306 α2,3- or α2,6-linked sialic acids 274:306 A species barrier for multiple viruses is present due to α2,3- or α2,6-linked sialic acids. 35648131 4 28 located present 602:608 arg1 horses 643:648 horses 643:648 horses 643:648 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 28 located present 602:608 arg1 mammals 618:624 most mammals 613:624 most mammals such as pigs and horses 613:648 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 28 located present 602:608 arg1 pigs 634:637 pigs 634:637 pigs 634:637 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 28 located present 602:608 arg2 Neu5Gc 592:597 Neu5Gc 592:597 Neu5Gc 592:597 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 7 29 theme Neu5Gc 1047:1052 arg1 content 1054:1060 Neu5Gc content 1047:1060 Neu5Gc content in wild Suidae, Cervidae, tigers, and European hedgehogs 1047:1117 We used these lectins to map Neu5Gc content in wild Suidae, Cervidae, tigers, and European hedgehogs. 35648131 6 30 theme developed 864:872 arg1 system 892:897 our previously developed tissue microarray system 849:897 our previously developed tissue microarray system 849:897 Using our previously developed tissue microarray system, we investigated how 2 different lectins specific for Neu5Gc can result in varying detection levels of Neu5Gc glycans. 35648131 9 31 theme tissues 1345:1351 arg1 treatment 1332:1340 methanol treatment 1323:1340 methanol treatment of tissues 1323:1351 Furthermore, the removal of N-linked glycans reduces the binding of both Neu5Gc lectins while retention of glycolipids by omitting methanol treatment of tissues increases lectin binding. 35648131 4 32 from absent 657:662 arg1 humans 667:672 humans 667:672 humans 667:672 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 32 from absent 657:662 arg1 ferrets 675:681 ferrets 675:681 ferrets 675:681 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 32 from absent 657:662 arg1 dogs 688:691 dogs 688:691 dogs 688:691 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 6 33 theme specific 940:947 arg1 lectins 932:938 2 different lectins 920:938 2 different lectins specific for Neu5Gc 920:958 Using our previously developed tissue microarray system, we investigated how 2 different lectins specific for Neu5Gc can result in varying detection levels of Neu5Gc glycans. 35648131 3 34 theme N-glycolylneuraminic 405:424 arg1 determinant 457:467 a determinant 455:467 a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus 455:589 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 3 34 theme N-glycolylneuraminic 405:424 arg1 Neu5Gc 432:437 Neu5Gc 432:437 Neu5Gc 432:437 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 3 34 theme N-glycolylneuraminic 405:424 arg1 acid 388:391 N-acetylneuraminic acid 369:391 N-acetylneuraminic acid (Neu5Ac) 369:400 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 3 34 theme N-glycolylneuraminic 405:424 arg1 acid 426:429 N-glycolylneuraminic acid 405:429 N-glycolylneuraminic acid (Neu5Gc) 405:438 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 0 35 theme domestic 9:16 arg1 animals 18:24 Wild and domestic animals 0:24 Wild and domestic animals 0:24 Wild and domestic animals variably display Neu5Ac and Neu5Gc sialic acids. 35648131 1 36 theme C-5 168:170 arg1 modifications 172:184 C-5 modifications 168:184 C-5 modifications 168:184 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 4 37 theme most 613:616 arg1 horses 643:648 horses 643:648 horses 643:648 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 37 theme most 613:616 arg1 mammals 618:624 most mammals 613:624 most mammals such as pigs and horses 613:648 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 37 theme most 613:616 arg1 pigs 634:637 pigs 634:637 pigs 634:637 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 38 attach present 602:608 arg1 horses 643:648 horses 643:648 horses 643:648 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 38 attach present 602:608 arg1 mammals 618:624 most mammals 613:624 most mammals such as pigs and horses 613:648 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 38 attach present 602:608 arg1 pigs 634:637 pigs 634:637 pigs 634:637 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 4 38 attach present 602:608 arg2 Neu5Gc 592:597 Neu5Gc 592:597 Neu5Gc 592:597 Neu5Gc is present in most mammals such as pigs and horses but is absent in humans, ferrets, and dogs. 35648131 5 39 theme C-5 769:771 arg1 acids 789:793 many C-5 modified sialic acids 764:793 many C-5 modified sialic acids 764:793 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 5 40 theme wildlife 740:747 arg1 species 749:755 wildlife species 740:755 wildlife species 740:755 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 10 41 theme single 1529:1534 arg1 lectin 1536:1541 a single lectin 1527:1541 a single lectin 1527:1541 These findings highlight the importance of using multiple Neu5Gc lectins as the rich variety in which Neu5Gc is displayed can hardly be detected by a single lectin. 35648131 9 42 theme glycans 1229:1235 arg1 removal 1209:1215 the removal 1205:1215 the removal of N-linked glycans 1205:1235 Furthermore, the removal of N-linked glycans reduces the binding of both Neu5Gc lectins while retention of glycolipids by omitting methanol treatment of tissues increases lectin binding. 35648131 5 43 theme many 764:767 arg1 acids 789:793 many C-5 modified sialic acids 764:793 many C-5 modified sialic acids 764:793 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 3 44 theme gastroenteritis 563:577 arg1 coronavirus 579:589 transmissible gastroenteritis coronavirus 549:589 transmissible gastroenteritis coronavirus 549:589 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 0 45 dep Neu5Ac 43:48 arg1 acids 68:72 sialic acids 61:72 sialic acids 61:72 Wild and domestic animals variably display Neu5Ac and Neu5Gc sialic acids. 35648131 1 46 from modifications 172:184 arg1 type 160:163 the linkage type 148:163 the linkage type 148:163 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 5 47 theme C-5 725:727 arg1 content 729:735 C-5 content 725:735 C-5 content in wildlife species 725:755 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 5 48 theme modified 773:780 arg1 acids 789:793 many C-5 modified sialic acids 764:793 many C-5 modified sialic acids 764:793 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 5 49 link N-linked 810:817 arg1 glycans 819:825 N-linked glycans 810:825 N-linked glycans 810:825 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 10 50 theme Neu5Gc 1437:1442 arg1 lectins 1444:1450 multiple Neu5Gc lectins 1428:1450 multiple Neu5Gc lectins 1428:1450 These findings highlight the importance of using multiple Neu5Gc lectins as the rich variety in which Neu5Gc is displayed can hardly be detected by a single lectin. 35648131 10 50 theme Neu5Gc 1437:1442 arg1 variety 1464:1470 the rich variety 1455:1470 the rich variety in which Neu5Gc is displayed can hardly be detected by a single lectin 1455:1541 These findings highlight the importance of using multiple Neu5Gc lectins as the rich variety in which Neu5Gc is displayed can hardly be detected by a single lectin. 35648131 3 51 theme influenza 515:523 arg1 virus 527:531 influenza A virus 515:531 influenza A virus 515:531 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 6 52 theme Neu5Gc 1002:1007 arg1 glycans 1009:1015 Neu5Gc glycans 1002:1015 Neu5Gc glycans 1002:1015 Using our previously developed tissue microarray system, we investigated how 2 different lectins specific for Neu5Gc can result in varying detection levels of Neu5Gc glycans. 35648131 1 53 used used 92:95 arg2 acids 82:86 Sialic acids 75:86 Sialic acids 75:86 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 1 53 used used 92:95 arg2 properties 205:214 the binding properties 193:214 the binding properties 193:214 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 1 53 used used 92:95 arg2 receptor 102:109 a receptor 100:109 a receptor 100:109 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 10 54 theme multiple 1428:1435 arg1 lectins 1444:1450 multiple Neu5Gc lectins 1428:1450 multiple Neu5Gc lectins 1428:1450 These findings highlight the importance of using multiple Neu5Gc lectins as the rich variety in which Neu5Gc is displayed can hardly be detected by a single lectin. 35648131 10 54 theme multiple 1428:1435 arg1 variety 1464:1470 the rich variety 1455:1470 the rich variety in which Neu5Gc is displayed can hardly be detected by a single lectin 1455:1541 These findings highlight the importance of using multiple Neu5Gc lectins as the rich variety in which Neu5Gc is displayed can hardly be detected by a single lectin. 35648131 3 55 theme A 525:525 arg1 virus 527:531 influenza A virus 515:531 influenza A virus 515:531 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 5 56 from content 729:735 arg1 species 749:755 wildlife species 740:755 wildlife species 740:755 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 5 57 theme N-linked 810:817 arg1 glycans 819:825 N-linked glycans 810:825 N-linked glycans 810:825 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 2 58 theme sialic 295:300 arg1 acids 302:306 α2,3- or α2,6-linked sialic acids 274:306 α2,3- or α2,6-linked sialic acids 274:306 A species barrier for multiple viruses is present due to α2,3- or α2,6-linked sialic acids. 35648131 6 59 theme glycans 1009:1015 arg1 levels 992:997 varying detection levels 974:997 varying detection levels of Neu5Gc glycans 974:1015 Using our previously developed tissue microarray system, we investigated how 2 different lectins specific for Neu5Gc can result in varying detection levels of Neu5Gc glycans. 35648131 6 60 theme different 922:930 arg1 lectins 932:938 2 different lectins 920:938 2 different lectins specific for Neu5Gc 920:958 Using our previously developed tissue microarray system, we investigated how 2 different lectins specific for Neu5Gc can result in varying detection levels of Neu5Gc glycans. 35648131 3 61 theme transmissible 549:561 arg1 coronavirus 579:589 transmissible gastroenteritis coronavirus 549:589 transmissible gastroenteritis coronavirus 549:589 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 2 62 theme α2,6-linked 283:293 arg1 acids 302:306 α2,3- or α2,6-linked sialic acids 274:306 α2,3- or α2,6-linked sialic acids 274:306 A species barrier for multiple viruses is present due to α2,3- or α2,6-linked sialic acids. 35648131 1 63 theme binding 197:203 arg1 properties 205:214 the binding properties 193:214 the binding properties 193:214 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 1 63 theme binding 197:203 arg1 receptor 102:109 a receptor 100:109 a receptor 100:109 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 1 63 theme binding 197:203 arg1 acids 82:86 Sialic acids 75:86 Sialic acids 75:86 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 0 64 theme sialic 61:66 arg1 acids 68:72 sialic acids 61:72 sialic acids 61:72 Wild and domestic animals variably display Neu5Ac and Neu5Gc sialic acids. 35648131 9 65 theme lectin 1363:1368 arg1 binding 1370:1376 lectin binding 1363:1376 lectin binding 1363:1376 Furthermore, the removal of N-linked glycans reduces the binding of both Neu5Gc lectins while retention of glycolipids by omitting methanol treatment of tissues increases lectin binding. 35648131 2 66 theme species 219:225 arg1 present 259:265 present 259:265 present 259:265 A species barrier for multiple viruses is present due to α2,3- or α2,6-linked sialic acids. 35648131 2 66 theme species 219:225 arg1 barrier 227:233 A species barrier 217:233 A species barrier for multiple viruses 217:254 A species barrier for multiple viruses is present due to α2,3- or α2,6-linked sialic acids. 35648131 8 67 theme Neu5Gc 1133:1138 arg1 content 1140:1146 Neu5Gc content 1133:1146 Neu5Gc content 1133:1146 We show that Neu5Gc content is highly variable among different species. 35648131 1 68 theme several 114:120 arg1 viruses 122:128 several viruses 114:128 several viruses 114:128 Sialic acids are used as a receptor by several viruses and variations in the linkage type or C-5 modifications affect the binding properties. 35648131 8 69 theme different 1173:1181 arg1 species 1183:1189 different species 1173:1189 different species 1173:1189 We show that Neu5Gc content is highly variable among different species. 35648131 9 70 theme Neu5Gc 1265:1270 arg1 lectins 1272:1278 both Neu5Gc lectins 1260:1278 both Neu5Gc lectins 1260:1278 Furthermore, the removal of N-linked glycans reduces the binding of both Neu5Gc lectins while retention of glycolipids by omitting methanol treatment of tissues increases lectin binding. 35648131 7 71 used used 1021:1024 arg2 We 1018:1019 We 1018:1019 We 1018:1019 We used these lectins to map Neu5Gc content in wild Suidae, Cervidae, tigers, and European hedgehogs. 35648131 9 72 theme methanol 1323:1330 arg1 treatment 1332:1340 methanol treatment 1323:1340 methanol treatment of tissues 1323:1351 Furthermore, the removal of N-linked glycans reduces the binding of both Neu5Gc lectins while retention of glycolipids by omitting methanol treatment of tissues increases lectin binding. 35648131 3 73 theme sialic 333:338 arg1 acid 340:343 the sialic acid 329:343 the sialic acid 329:343 The C-5 position of the sialic acid can be modified to form N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), which acts as a determinant for host susceptibility for pathogens such as influenza A virus, rotavirus, and transmissible gastroenteritis coronavirus. 35648131 5 74 theme sialic 782:787 arg1 acids 789:793 many C-5 modified sialic acids 764:793 many C-5 modified sialic acids 764:793 However, little is known about C-5 content in wildlife species or how many C-5 modified sialic acids are present on N-linked glycans or glycolipids. 35648131 9 75 theme lectins 1272:1278 arg1 binding 1249:1255 the binding 1245:1255 the binding of both Neu5Gc lectins 1245:1278 Furthermore, the removal of N-linked glycans reduces the binding of both Neu5Gc lectins while retention of glycolipids by omitting methanol treatment of tissues increases lectin binding. 36741455 5 0 theme AA 716:717 arg1 deletion 719:726 This single AA deletion 704:726 This single AA deletion 704:726 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 2 1 theme human 338:342 arg1 infections 344:353 serious human infections 330:353 serious human infections 330:353 Among them, only H5N6 viruses are frequently reported to infect mammals and cause serious human infections. 36741455 4 2 theme Phylogenetic 552:563 arg1 analysis 565:572 Phylogenetic analysis 552:572 Phylogenetic analysis 552:572 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 6 3 dep increases 1133:1141 arg1 stabilizes 1181:1190 stabilizes 1181:1190 thus stabilizes the trimeric structure 1176:1213 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 2 4 theme serious 330:336 arg1 infections 344:353 serious human infections 330:353 serious human infections 330:353 Among them, only H5N6 viruses are frequently reported to infect mammals and cause serious human infections. 36741455 4 5 attach isolated 674:681 arg1 patients 694:701 human patients 688:701 human patients 688:701 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 4 5 attach isolated 674:681 arg2 virus 668:672 H5N6 virus 663:672 H5N6 virus isolated from human patients 663:701 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 3 6 from viruses 484:490 arg1 HA 440:441 HA 440:441 HA 440:441 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 3 6 from viruses 484:490 arg1 characteristics 398:412 the genetic and biological characteristics 371:412 the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 371:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 3 6 from viruses 484:490 arg1 hemagglutinin 425:437 surface hemagglutinin 417:437 surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 417:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 7 7 theme mammalian 1348:1356 arg1 hosts 1358:1362 mammalian hosts 1348:1362 mammalian hosts 1348:1362 Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts. 36741455 4 8 theme human 688:692 arg1 patients 694:701 human patients 688:701 human patients 688:701 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 5 9 from replication 760:770 arg1 vitro 793:797 vitro 793:797 vitro 793:797 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 5 9 from replication 760:770 arg1 hosts 816:820 mammalian hosts 806:820 mammalian hosts (mice and ferrets) 806:839 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 2 10 theme H5N6 265:268 arg1 viruses 270:276 only H5N6 viruses 260:276 only H5N6 viruses 260:276 Among them, only H5N6 viruses are frequently reported to infect mammals and cause serious human infections. 36741455 6 11 theme trimeric 1196:1203 arg1 structure 1205:1213 the trimeric structure 1192:1213 the trimeric structure 1192:1213 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 3 12 theme influenza 474:482 arg1 viruses 484:490 clade 2.3.4.4 H5Ny avian influenza viruses 449:490 clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 449:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 3 12 theme influenza 474:482 arg1 AIVs 493:496 AIVs 493:496 AIVs 493:496 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 5 13 from pH 934:935 arg1 threshold 919:927 reduced pH threshold 908:927 reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion 908:982 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 4 14 theme virus 668:672 arg1 deletion 604:611 an amino acid (AA) deletion 585:611 an amino acid (AA) deletion 585:611 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 4 14 theme virus 668:672 arg1 feature 652:658 a distinctive feature 638:658 a distinctive feature of H5N6 virus isolated from human patients 638:701 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 1 15 theme Clade 120:124 arg1 H5N8 177:180 H5N8 177:180 H5N8 177:180 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 15 theme Clade 120:124 arg1 H5N6 167:170 H5N6 167:170 H5N6 167:170 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 15 theme Clade 120:124 arg1 viruses 145:151 Clade 2.3.4.4 avian H5Ny viruses 120:151 Clade 2.3.4.4 avian H5Ny viruses 120:151 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 15 theme Clade 120:124 arg1 H5N2 161:164 H5N2 161:164 H5N2 161:164 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 7 16 theme virus 1329:1333 arg1 infection 1335:1343 cross-species avian H5N6 virus infection 1304:1343 cross-species avian H5N6 virus infection to mammalian hosts 1304:1362 Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts. 36741455 0 17 link N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation 0:21 N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals. 36741455 2 18 theme only 260:263 arg1 viruses 270:276 only H5N6 viruses 260:276 only H5N6 viruses 260:276 Among them, only H5N6 viruses are frequently reported to infect mammals and cause serious human infections. 36741455 5 19 theme protein 852:858 arg1 acid 860:863 HA protein acid and thermal stabilization 849:889 acid 860:863 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 3 20 theme surface 417:423 arg1 HA 440:441 HA 440:441 HA 440:441 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 3 20 theme surface 417:423 arg1 hemagglutinin 425:437 surface hemagglutinin 417:437 surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 417:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 3 21 theme genetic 375:381 arg1 characteristics 398:412 the genetic and biological characteristics 371:412 the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 371:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 6 22 link N-linked 1091:1098 arg1 site 1114:1117 an N-linked glycosylation site 1088:1117 an N-linked glycosylation site 1088:1117 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 5 23 theme virus 754:758 arg1 replication 760:770 H5N6 virus replication 749:770 H5N6 virus replication 749:770 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 3 24 theme hemagglutinin 425:437 arg1 characteristics 398:412 the genetic and biological characteristics 371:412 the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 371:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 5 25 theme H5N6 749:752 arg1 replication 760:770 H5N6 virus replication 749:770 H5N6 virus replication 749:770 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 6 26 from deletion 1046:1053 arg1 HA 1058:1059 HA 1058:1059 HA 1058:1059 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 3 27 theme mammalian 531:539 arg1 infection 541:549 mammalian infection 531:549 mammalian infection 531:549 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 4 28 theme HA 632:633 arg1 position 616:623 position 131 616:627 position 131 of HA 616:633 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 0 29 theme N-linked 0:7 arg1 glycosylation 9:21 N-linked glycosylation 0:21 N-linked glycosylation 0:21 N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals. 36741455 5 30 theme thermal 869:875 arg1 stabilization 877:889 HA protein acid and thermal stabilization 849:889 stabilization 877:889 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 6 31 gly glycosylation 1100:1112 arg2 site 1114:1117 an N-linked glycosylation site 1088:1117 an N-linked glycosylation site 1088:1117 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 0 32 theme hemagglutinin 32:44 arg1 stability 46:54 hemagglutinin stability 32:54 hemagglutinin stability 32:54 N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals. 36741455 6 33 theme crystal 1007:1013 arg1 structure 1015:1023 crystal structure 1007:1023 crystal structure 1007:1023 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 7 34 theme H5N6 1324:1327 arg1 virus 1329:1333 cross-species avian H5N6 virus 1304:1333 cross-species avian H5N6 virus infection to mammalian hosts 1304:1362 Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts. 36741455 6 35 from position 1064:1071 arg1 deletion 1046:1053 the AA deletion 1039:1053 the AA deletion in HA at position 131 1039:1075 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 5 36 dep pH 934:935 arg1 to 941:942 to 941:942 to 941:942 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 5 37 theme reduced 908:914 arg1 threshold 919:927 reduced pH threshold 908:927 reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion 908:982 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 4 38 theme distinctive 640:650 arg1 deletion 604:611 an amino acid (AA) deletion 585:611 an amino acid (AA) deletion 585:611 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 4 38 theme distinctive 640:650 arg1 feature 652:658 a distinctive feature 638:658 a distinctive feature of H5N6 virus isolated from human patients 638:701 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 7 39 theme molecular 1239:1247 arg1 understanding 1249:1261 a molecular understanding 1237:1261 a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts 1237:1362 Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts. 36741455 5 40 theme HA 849:850 arg1 acid 860:863 HA protein acid and thermal stabilization 849:889 acid 860:863 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 5 41 dep hosts 816:820 arg1 ferrets 832:838 ferrets 832:838 ferrets 832:838 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 5 41 dep hosts 816:820 arg1 mice 823:826 mice 823:826 mice 823:826 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 3 42 theme biological 387:396 arg1 characteristics 398:412 the genetic and biological characteristics 371:412 the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 371:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 6 43 theme HA 1163:1164 arg1 monomers 1166:1173 HA monomers 1163:1173 HA monomers 1163:1173 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 0 44 theme H5N6 65:68 arg1 virus 80:84 avian H5N6 influenza virus to promote adaptation in mammals 59:117 avian H5N6 influenza virus to promote adaptation in mammals 59:117 N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals. 36741455 1 45 from spread 229:234 arg1 poultry 239:245 poultry 239:245 poultry 239:245 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 5 46 theme single 709:714 arg1 deletion 719:726 This single AA deletion 704:726 This single AA deletion 704:726 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 7 47 theme avian 1318:1322 arg1 virus 1329:1333 cross-species avian H5N6 virus 1304:1333 cross-species avian H5N6 virus infection to mammalian hosts 1304:1362 Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts. 36741455 6 48 theme N-linked 1091:1098 arg1 site 1114:1117 an N-linked glycosylation site 1088:1117 an N-linked glycosylation site 1088:1117 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 3 49 theme H5Ny 463:466 arg1 viruses 484:490 clade 2.3.4.4 H5Ny avian influenza viruses 449:490 clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 449:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 3 49 theme H5Ny 463:466 arg1 AIVs 493:496 AIVs 493:496 AIVs 493:496 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 0 50 theme avian 59:63 arg1 virus 80:84 avian H5N6 influenza virus to promote adaptation in mammals 59:117 avian H5N6 influenza virus to promote adaptation in mammals 59:117 N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals. 36741455 3 51 theme clade 449:453 arg1 viruses 484:490 clade 2.3.4.4 H5Ny avian influenza viruses 449:490 clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 449:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 3 51 theme clade 449:453 arg1 AIVs 493:496 AIVs 493:496 AIVs 493:496 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 5 52 theme membrane 968:975 arg1 fusion 977:982 viral-endosomal membrane fusion 952:982 viral-endosomal membrane fusion 952:982 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 5 53 theme viral-endosomal 952:966 arg1 fusion 977:982 viral-endosomal membrane fusion 952:982 viral-endosomal membrane fusion 952:982 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 5 54 from pathogenicity 776:788 arg1 vitro 793:797 vitro 793:797 vitro 793:797 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 5 54 from pathogenicity 776:788 arg1 hosts 816:820 mammalian hosts 806:820 mammalian hosts (mice and ferrets) 806:839 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 3 55 theme avian 468:472 arg1 viruses 484:490 clade 2.3.4.4 H5Ny avian influenza viruses 449:490 clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 449:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 3 55 theme avian 468:472 arg1 AIVs 493:496 AIVs 493:496 AIVs 493:496 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 3 56 from adaptation 517:526 arg1 infection 541:549 mammalian infection 531:549 mammalian infection 531:549 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 4 57 theme H5N6 663:666 arg1 virus 668:672 H5N6 virus 663:672 H5N6 virus isolated from human patients 663:701 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 6 58 theme glycosylation 1100:1112 arg1 site 1114:1117 an N-linked glycosylation site 1088:1117 an N-linked glycosylation site 1088:1117 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 7 59 theme HA 1270:1271 arg1 stabilization 1281:1293 HA protein stabilization 1270:1293 HA protein stabilization 1270:1293 Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts. 36741455 1 60 theme avian 134:138 arg1 H5N8 177:180 H5N8 177:180 H5N8 177:180 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 60 theme avian 134:138 arg1 H5N6 167:170 H5N6 167:170 H5N6 167:170 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 60 theme avian 134:138 arg1 viruses 145:151 Clade 2.3.4.4 avian H5Ny viruses 120:151 Clade 2.3.4.4 avian H5Ny viruses 120:151 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 60 theme avian 134:138 arg1 H5N2 161:164 H5N2 161:164 H5N2 161:164 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 61 theme unprecedented 198:210 arg1 spread 229:234 unprecedented intercontinental spread 198:234 unprecedented intercontinental spread in poultry 198:245 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 5 62 theme pH 916:917 arg1 threshold 919:927 reduced pH threshold 908:927 reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion 908:982 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 7 63 theme cross-species 1304:1316 arg1 virus 1329:1333 cross-species avian H5N6 virus 1304:1333 cross-species avian H5N6 virus infection to mammalian hosts 1304:1362 Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts. 36741455 3 64 from characteristics 398:412 arg1 viruses 484:490 clade 2.3.4.4 H5Ny avian influenza viruses 449:490 clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) 449:497 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 3 64 from characteristics 398:412 arg1 AIVs 493:496 AIVs 493:496 AIVs 493:496 In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. 36741455 1 65 theme H5Ny 140:143 arg1 H5N8 177:180 H5N8 177:180 H5N8 177:180 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 65 theme H5Ny 140:143 arg1 H5N6 167:170 H5N6 167:170 H5N6 167:170 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 65 theme H5Ny 140:143 arg1 viruses 145:151 Clade 2.3.4.4 avian H5Ny viruses 120:151 Clade 2.3.4.4 avian H5Ny viruses 120:151 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 65 theme H5Ny 140:143 arg1 H5N2 161:164 H5N2 161:164 H5N2 161:164 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 1 66 theme intercontinental 212:227 arg1 spread 229:234 unprecedented intercontinental spread 198:234 unprecedented intercontinental spread in poultry 198:245 Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. 36741455 0 67 from adaptation 97:106 arg1 mammals 111:117 mammals 111:117 mammals 111:117 N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals. 36741455 7 68 theme protein 1273:1279 arg1 stabilization 1281:1293 HA protein stabilization 1270:1293 HA protein stabilization 1270:1293 Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts. 36741455 6 69 theme Mass 985:988 arg1 spectrometry 990:1001 Mass spectrometry 985:1001 Mass spectrometry 985:1001 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 6 70 theme AA 1043:1044 arg1 deletion 1046:1053 the AA deletion 1039:1053 the AA deletion in HA at position 131 1039:1075 Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. 36741455 5 71 theme mammalian 806:814 arg1 hosts 816:820 mammalian hosts 806:820 mammalian hosts (mice and ferrets) 806:839 This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. 36741455 0 72 theme influenza 70:78 arg1 virus 80:84 avian H5N6 influenza virus to promote adaptation in mammals 59:117 avian H5N6 influenza virus to promote adaptation in mammals 59:117 N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals. 36741455 4 73 theme amino 588:592 arg1 AA 600:601 AA 600:601 AA 600:601 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 4 73 theme amino 588:592 arg1 acid 594:597 amino acid 588:597 an amino acid (AA) deletion 585:611 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 4 74 theme acid 594:597 arg1 deletion 604:611 an amino acid (AA) deletion 585:611 an amino acid (AA) deletion 585:611 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 36741455 4 74 theme acid 594:597 arg1 feature 652:658 a distinctive feature 638:658 a distinctive feature of H5N6 virus isolated from human patients 638:701 Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. 35385654 6 0 theme direct 1197:1202 arg1 injection/analysis 1204:1221 direct injection/analysis 1197:1221 direct injection/analysis 1197:1221 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 2 1 theme technology 383:392 arg1 use 348:350 the use 344:350 the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production 344:504 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 6 2 from enrichment 1182:1191 arg1 system 1279:1284 an integrated high-performance liquid chromatography system 1226:1284 an integrated high-performance liquid chromatography system 1226:1284 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 7 3 theme aqueous 1386:1392 arg1 conditions 1394:1403 aqueous conditions 1386:1403 aqueous conditions 1386:1403 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 9 4 theme ovary 1985:1989 arg1 cells 1991:1995 Chinese hamster ovary cells 1969:1995 Chinese hamster ovary cells 1969:1995 Finally, we showcase how the N-GLYcanyzer platform can be implemented at-/online in an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells. 35385654 3 5 theme critical 595:602 arg1 glycosylation 570:582 N-linked glycosylation 561:582 N-linked glycosylation 561:582 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 3 5 theme critical 595:602 arg1 attributes 612:621 critical quality attributes 595:621 critical quality attributes that affect biologics' safety and efficacy 595:664 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 3 5 theme critical 595:602 arg1 modifications 526:538 Post-translational modifications 507:538 Post-translational modifications 507:538 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 4 6 theme online 738:743 arg1 system 776:781 an online sequential-injection-based PAT system 735:781 an online sequential-injection-based PAT system 735:781 Here, we developed an online sequential-injection-based PAT system, called N-GLYcanyzer, which can rapidly monitor mAb glycosylation during upstream biomanufacturing. 35385654 2 7 theme advanced 355:362 arg1 PAT 395:397 PAT 395:397 PAT 395:397 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 2 7 theme advanced 355:362 arg1 technology 383:392 advanced process analytical technology 355:392 advanced process analytical technology (PAT) 355:398 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 5 8 theme sample 972:977 arg1 derivation 979:988 fully automated sample derivation 956:988 fully automated sample derivation 956:988 The key innovation includes the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis within 3 h. 35385654 3 9 link N-linked 561:568 arg1 glycosylation 570:582 N-linked glycosylation 561:582 N-linked glycosylation 561:582 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 5 10 theme integrated 928:937 arg1 system 990:995 an integrated mAb sampling and fully automated sample derivation system 925:995 an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis 925:1037 The key innovation includes the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis within 3 h. 35385654 5 11 theme sampling 943:950 arg1 system 990:995 an integrated mAb sampling and fully automated sample derivation system 925:995 an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis 925:1037 The key innovation includes the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis within 3 h. 35385654 9 12 theme automated 1875:1883 arg1 monitoring 1918:1927 automated and near-real-time glycosylation monitoring 1875:1927 automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells 1875:1995 Finally, we showcase how the N-GLYcanyzer platform can be implemented at-/online in an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells. 35385654 6 13 with labeling 1131:1138 arg1 dyes 1157:1160 fluorescent dyes 1145:1160 fluorescent dyes 1145:1160 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 9 14 theme near-real-time 1889:1902 arg1 monitoring 1918:1927 automated and near-real-time glycosylation monitoring 1875:1927 automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells 1875:1995 Finally, we showcase how the N-GLYcanyzer platform can be implemented at-/online in an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells. 35385654 8 15 theme N-GLYcanyzer 1605:1616 arg1 workflow 1618:1625 the N-GLYcanyzer workflow 1601:1625 the N-GLYcanyzer workflow 1601:1625 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 6 16 with capture 1089:1095 arg1 dyes 1157:1160 fluorescent dyes 1145:1160 fluorescent dyes 1145:1160 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 4 17 theme mAb 831:833 arg1 glycosylation 835:847 mAb glycosylation 831:847 mAb glycosylation 831:847 Here, we developed an online sequential-injection-based PAT system, called N-GLYcanyzer, which can rapidly monitor mAb glycosylation during upstream biomanufacturing. 35385654 2 18 theme regulatory 305:314 arg1 agencies 316:323 Federal regulatory agencies 297:323 Federal regulatory agencies 297:323 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 6 19 theme glycan 1124:1129 arg1 labeling 1131:1138 released glycan labeling 1115:1138 released glycan labeling with fluorescent dyes 1115:1160 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 6 20 with deglycosylation 1098:1112 arg1 dyes 1157:1160 fluorescent dyes 1145:1160 fluorescent dyes 1145:1160 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 4 21 theme PAT 772:774 arg1 system 776:781 an online sequential-injection-based PAT system 735:781 an online sequential-injection-based PAT system 735:781 Here, we developed an online sequential-injection-based PAT system, called N-GLYcanyzer, which can rapidly monitor mAb glycosylation during upstream biomanufacturing. 35385654 0 22 theme Monoclonal 67:76 arg1 Glycosylation 96:108 Monoclonal Antibody N-Linked Glycosylation 67:108 Monoclonal Antibody N-Linked Glycosylation 67:108 Integrated Process Analytical Platform for Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation. 35385654 3 23 theme close 677:681 arg1 monitoring 683:692 close monitoring 677:692 close monitoring 677:692 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 5 24 theme system 990:995 arg1 design 915:920 the design 911:920 the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis 911:1037 The key innovation includes the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis within 3 h. 35385654 8 25 theme higher 1634:1639 arg1 efficiency 1657:1666 higher glycan labeling efficiency 1634:1666 higher glycan labeling efficiency 1634:1666 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 8 26 with labeling 1531:1538 arg1 borane 1567:1572 2-picoline borane 1556:1572 2-picoline borane as a reducing agent 1556:1592 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 0 27 theme N-Linked 87:94 arg1 Glycosylation 96:108 Monoclonal Antibody N-Linked Glycosylation 67:108 Monoclonal Antibody N-Linked Glycosylation 67:108 Integrated Process Analytical Platform for Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation. 35385654 1 28 theme biomanufacturing 193:208 arg1 practices 210:218 continuous biomanufacturing practices 182:218 continuous biomanufacturing practices that are often more flexible and efficient than traditional batch processes 182:294 The biopharmaceutical industry is transitioning toward the adoption of continuous biomanufacturing practices that are often more flexible and efficient than traditional batch processes. 35385654 9 29 theme biosimilar 1946:1955 arg1 monitoring 1918:1927 automated and near-real-time glycosylation monitoring 1875:1927 automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells 1875:1995 Finally, we showcase how the N-GLYcanyzer platform can be implemented at-/online in an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells. 35385654 8 30 theme labeling 1648:1655 arg1 efficiency 1657:1666 higher glycan labeling efficiency 1634:1666 higher glycan labeling efficiency 1634:1666 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 6 31 from labeling 1131:1138 arg1 system 1279:1284 an integrated high-performance liquid chromatography system 1226:1284 an integrated high-performance liquid chromatography system 1226:1284 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 6 32 theme mAb 1085:1087 arg1 capture 1089:1095 mAb capture 1085:1095 mAb capture 1085:1095 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 6 33 from capture 1089:1095 arg1 system 1279:1284 an integrated high-performance liquid chromatography system 1226:1284 an integrated high-performance liquid chromatography system 1226:1284 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 5 34 theme antibody 1001:1008 arg1 titer 1010:1014 antibody titer 1001:1014 antibody titer 1001:1014 The key innovation includes the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis within 3 h. 35385654 6 35 theme glycan 1175:1180 arg1 enrichment 1182:1191 labeled glycan enrichment 1167:1191 labeled glycan enrichment 1167:1191 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 9 36 theme hamster 1977:1983 arg1 cells 1991:1995 Chinese hamster ovary cells 1969:1995 Chinese hamster ovary cells 1969:1995 Finally, we showcase how the N-GLYcanyzer platform can be implemented at-/online in an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells. 35385654 6 37 from deglycosylation 1098:1112 arg1 system 1279:1284 an integrated high-performance liquid chromatography system 1226:1284 an integrated high-performance liquid chromatography system 1226:1284 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 2 38 theme high-quality 473:484 arg1 production 495:504 high-quality biologic production 473:504 high-quality biologic production 473:504 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 7 39 used used 1448:1451 arg2 PGC 1439:1441 PGC 1439:1441 PGC 1439:1441 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 7 39 used used 1448:1451 arg2 carbon 1431:1436 porous graphitized carbon 1412:1436 porous graphitized carbon (PGC) 1412:1442 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 0 40 theme Analytical 19:28 arg1 Platform 30:37 Process Analytical Platform 11:37 Process Analytical Platform for Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation 11:108 Integrated Process Analytical Platform for Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation. 35385654 8 41 theme glycans 1543:1549 arg1 labeling 1531:1538 2-aminobenzamide labeling 1514:1538 2-aminobenzamide labeling 1514:1538 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 2 42 theme process 444:450 arg1 knowledge 452:460 the process knowledge 440:460 the process knowledge 440:460 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 7 43 theme Different 1287:1295 arg1 tags 1309:1312 Different fluorescent tags 1287:1312 Different fluorescent tags 1287:1312 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 6 44 with enrichment 1182:1191 arg1 dyes 1157:1160 fluorescent dyes 1145:1160 fluorescent dyes 1145:1160 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 8 45 theme 5-fold 1714:1719 arg1 increase 1721:1728 a 5-fold increase 1712:1728 a 5-fold increase in fluorescent product intensity 1712:1761 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 8 46 theme 2-picoline 1556:1565 arg1 borane 1567:1572 2-picoline borane 1556:1572 2-picoline borane as a reducing agent 1556:1592 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 6 47 gly deglycosylation 1098:1112 arg1 system 1279:1284 an integrated high-performance liquid chromatography system 1226:1284 an integrated high-performance liquid chromatography system 1226:1284 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 6 48 theme high-performance 1240:1255 arg1 chromatography 1264:1277 high-performance liquid chromatography 1240:1277 an integrated high-performance liquid chromatography system 1226:1284 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 3 49 theme proteins 543:550 arg1 glycosylation 570:582 N-linked glycosylation 561:582 N-linked glycosylation 561:582 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 3 49 theme proteins 543:550 arg1 attributes 612:621 critical quality attributes 595:621 critical quality attributes that affect biologics' safety and efficacy 595:664 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 3 49 theme proteins 543:550 arg1 modifications 526:538 Post-translational modifications 507:538 Post-translational modifications 507:538 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 7 50 theme graphitized 1419:1429 arg1 PGC 1439:1441 PGC 1439:1441 PGC 1439:1441 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 7 50 theme graphitized 1419:1429 arg1 carbon 1431:1436 porous graphitized carbon 1412:1436 porous graphitized carbon (PGC) 1412:1442 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 8 51 theme product 1745:1751 arg1 intensity 1753:1761 fluorescent product intensity 1733:1761 fluorescent product intensity 1733:1761 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 8 52 theme reducing 1579:1586 arg1 agent 1588:1592 a reducing agent 1577:1592 a reducing agent 1577:1592 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 1 53 theme batch 280:284 arg1 processes 286:294 traditional batch processes 268:294 traditional batch processes 268:294 The biopharmaceutical industry is transitioning toward the adoption of continuous biomanufacturing practices that are often more flexible and efficient than traditional batch processes. 35385654 7 54 theme glycan 1353:1358 arg1 efficiency 1369:1378 glycan labeling efficiency 1353:1378 glycan labeling efficiency 1353:1378 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 3 55 theme N-linked 561:568 arg1 glycosylation 570:582 N-linked glycosylation 561:582 N-linked glycosylation 561:582 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 9 56 theme N-GLYcanyzer 1793:1804 arg1 platform 1806:1813 the N-GLYcanyzer platform 1789:1813 the N-GLYcanyzer platform 1789:1813 Finally, we showcase how the N-GLYcanyzer platform can be implemented at-/online in an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells. 35385654 3 57 theme quality 604:610 arg1 glycosylation 570:582 N-linked glycosylation 561:582 N-linked glycosylation 561:582 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 3 57 theme quality 604:610 arg1 attributes 612:621 critical quality attributes 595:621 critical quality attributes that affect biologics' safety and efficacy 595:664 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 3 57 theme quality 604:610 arg1 modifications 526:538 Post-translational modifications 507:538 Post-translational modifications 507:538 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 1 58 theme practices 210:218 arg1 adoption 170:177 the adoption 166:177 the adoption of continuous biomanufacturing practices that are often more flexible and efficient than traditional batch processes 166:294 The biopharmaceutical industry is transitioning toward the adoption of continuous biomanufacturing practices that are often more flexible and efficient than traditional batch processes. 35385654 7 59 theme labeling 1360:1367 arg1 efficiency 1369:1378 glycan labeling efficiency 1353:1378 glycan labeling efficiency 1353:1378 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 8 60 from increase 1721:1728 arg1 intensity 1753:1761 fluorescent product intensity 1733:1761 fluorescent product intensity 1733:1761 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 2 61 theme process 364:370 arg1 PAT 395:397 PAT 395:397 PAT 395:397 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 2 61 theme process 364:370 arg1 technology 383:392 advanced process analytical technology 355:392 advanced process analytical technology (PAT) 355:398 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 5 62 theme automated 962:970 arg1 derivation 979:988 fully automated sample derivation 956:988 fully automated sample derivation 956:988 The key innovation includes the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis within 3 h. 35385654 6 63 theme N-GLYcanyzer 1055:1066 arg1 process 1068:1074 The N-GLYcanyzer process 1051:1074 The N-GLYcanyzer process 1051:1074 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 9 64 theme upstream 1851:1858 arg1 bioreactor 1860:1869 an upstream bioreactor 1848:1869 an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells 1848:1995 Finally, we showcase how the N-GLYcanyzer platform can be implemented at-/online in an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells. 35385654 6 65 theme chromatography 1264:1277 arg1 system 1279:1284 an integrated high-performance liquid chromatography system 1226:1284 an integrated high-performance liquid chromatography system 1226:1284 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 5 66 theme mAb 939:941 arg1 sampling 943:950 mAb sampling 939:950 mAb sampling 939:950 The key innovation includes the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis within 3 h. 35385654 5 67 theme glycoform 1020:1028 arg1 analysis 1030:1037 glycoform analysis 1020:1037 glycoform analysis 1020:1037 The key innovation includes the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis within 3 h. 35385654 9 68 theme glycosylation 1904:1916 arg1 monitoring 1918:1927 automated and near-real-time glycosylation monitoring 1875:1927 automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells 1875:1995 Finally, we showcase how the N-GLYcanyzer platform can be implemented at-/online in an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells. 35385654 6 69 theme integrated 1229:1238 arg1 system 1279:1284 an integrated high-performance liquid chromatography system 1226:1284 an integrated high-performance liquid chromatography system 1226:1284 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 0 70 theme Antibody 78:85 arg1 Glycosylation 96:108 Monoclonal Antibody N-Linked Glycosylation 67:108 Monoclonal Antibody N-Linked Glycosylation 67:108 Integrated Process Analytical Platform for Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation. 35385654 2 71 theme Federal 297:303 arg1 agencies 316:323 Federal regulatory agencies 297:323 Federal regulatory agencies 297:323 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 5 72 theme derivation 979:988 arg1 system 990:995 an integrated mAb sampling and fully automated sample derivation system 925:995 an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis 925:1037 The key innovation includes the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis within 3 h. 35385654 6 73 theme released 1115:1122 arg1 labeling 1131:1138 released glycan labeling 1115:1138 released glycan labeling with fluorescent dyes 1115:1160 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 8 74 theme glycan 1641:1646 arg1 efficiency 1657:1666 higher glycan labeling efficiency 1634:1666 higher glycan labeling efficiency 1634:1666 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 4 75 theme sequential-injection-based 745:770 arg1 system 776:781 an online sequential-injection-based PAT system 735:781 an online sequential-injection-based PAT system 735:781 Here, we developed an online sequential-injection-based PAT system, called N-GLYcanyzer, which can rapidly monitor mAb glycosylation during upstream biomanufacturing. 35385654 0 76 theme Glycosylation 96:108 arg1 Monitoring 53:62 Automated Monitoring 43:62 Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation 43:108 Integrated Process Analytical Platform for Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation. 35385654 1 77 theme continuous 182:191 arg1 practices 210:218 continuous biomanufacturing practices 182:218 continuous biomanufacturing practices that are often more flexible and efficient than traditional batch processes 182:294 The biopharmaceutical industry is transitioning toward the adoption of continuous biomanufacturing practices that are often more flexible and efficient than traditional batch processes. 35385654 9 78 theme Trastuzumab 1934:1944 arg1 biosimilar 1946:1955 a Trastuzumab biosimilar 1932:1955 a Trastuzumab biosimilar produced by Chinese hamster ovary cells 1932:1995 Finally, we showcase how the N-GLYcanyzer platform can be implemented at-/online in an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells. 35385654 8 79 theme aqueous 1674:1680 arg1 conditions 1682:1691 aqueous conditions 1674:1691 aqueous conditions 1674:1691 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 7 80 theme glycan 1468:1473 arg1 recovery 1475:1482 glycan recovery 1468:1482 glycan recovery 1468:1482 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 9 81 theme Chinese 1969:1975 arg1 cells 1991:1995 Chinese hamster ovary cells 1969:1995 Chinese hamster ovary cells 1969:1995 Finally, we showcase how the N-GLYcanyzer platform can be implemented at-/online in an upstream bioreactor for automated and near-real-time glycosylation monitoring of a Trastuzumab biosimilar produced by Chinese hamster ovary cells. 35385654 4 82 theme upstream 856:863 arg1 biomanufacturing 865:880 upstream biomanufacturing 856:880 upstream biomanufacturing 856:880 Here, we developed an online sequential-injection-based PAT system, called N-GLYcanyzer, which can rapidly monitor mAb glycosylation during upstream biomanufacturing. 35385654 0 83 theme Process 11:17 arg1 Platform 30:37 Process Analytical Platform 11:37 Process Analytical Platform for Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation 11:108 Integrated Process Analytical Platform for Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation. 35385654 6 84 theme labeled 1167:1173 arg1 enrichment 1182:1191 labeled glycan enrichment 1167:1191 labeled glycan enrichment 1167:1191 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 2 85 theme biologic 486:493 arg1 production 495:504 high-quality biologic production 473:504 high-quality biologic production 473:504 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 2 86 theme design 415:420 arg1 space 422:426 the design space 411:426 the design space 411:426 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 7 87 theme fluorescent 1297:1307 arg1 tags 1309:1312 Different fluorescent tags 1287:1312 Different fluorescent tags 1287:1312 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 1 88 theme biopharmaceutical 115:131 arg1 transitioning 145:157 transitioning 145:157 transitioning 145:157 The biopharmaceutical industry is transitioning toward the adoption of continuous biomanufacturing practices that are often more flexible and efficient than traditional batch processes. 35385654 1 88 theme biopharmaceutical 115:131 arg1 industry 133:140 The biopharmaceutical industry 111:140 The biopharmaceutical industry 111:140 The biopharmaceutical industry is transitioning toward the adoption of continuous biomanufacturing practices that are often more flexible and efficient than traditional batch processes. 35385654 8 89 theme 2-aminobenzamide 1514:1529 arg1 labeling 1531:1538 2-aminobenzamide labeling 1514:1538 2-aminobenzamide labeling 1514:1538 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 0 90 theme Automated 43:51 arg1 Monitoring 53:62 Automated Monitoring 43:62 Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation 43:108 Integrated Process Analytical Platform for Automated Monitoring of Monoclonal Antibody N-Linked Glycosylation. 35385654 6 91 theme fluorescent 1145:1155 arg1 dyes 1157:1160 fluorescent dyes 1145:1160 fluorescent dyes 1145:1160 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 3 92 theme Post-translational 507:524 arg1 glycosylation 570:582 N-linked glycosylation 561:582 N-linked glycosylation 561:582 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 3 92 theme Post-translational 507:524 arg1 attributes 612:621 critical quality attributes 595:621 critical quality attributes that affect biologics' safety and efficacy 595:664 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 3 92 theme Post-translational 507:524 arg1 modifications 526:538 Post-translational modifications 507:538 Post-translational modifications 507:538 Post-translational modifications of proteins, such as N-linked glycosylation, are often critical quality attributes that affect biologics' safety and efficacy, requiring close monitoring during manufacturing. 35385654 5 93 theme key 887:889 arg1 innovation 891:900 The key innovation 883:900 The key innovation 883:900 The key innovation includes the design of an integrated mAb sampling and fully automated sample derivation system for antibody titer and glycoform analysis within 3 h. 35385654 6 94 theme liquid 1257:1262 arg1 chromatography 1264:1277 high-performance liquid chromatography 1240:1277 an integrated high-performance liquid chromatography system 1226:1284 The N-GLYcanyzer process includes mAb capture, deglycosylation, released glycan labeling with fluorescent dyes, and labeled glycan enrichment for direct injection/analysis on an integrated high-performance liquid chromatography system. 35385654 8 95 theme fluorescent 1733:1743 arg1 intensity 1753:1761 fluorescent product intensity 1733:1761 fluorescent product intensity 1733:1761 We found that 2-aminobenzamide labeling of glycans with 2-picoline borane as a reducing agent, using the N-GLYcanyzer workflow, shows higher glycan labeling efficiency under aqueous conditions, leading upward to a 5-fold increase in fluorescent product intensity. 35385654 7 96 theme porous 1412:1417 arg1 PGC 1439:1441 PGC 1439:1441 PGC 1439:1441 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 7 96 theme porous 1412:1417 arg1 carbon 1431:1436 porous graphitized carbon 1412:1436 porous graphitized carbon (PGC) 1412:1442 Different fluorescent tags and reductants were tested to maximize glycan labeling efficiency under aqueous conditions, while porous graphitized carbon (PGC) was used for optimizing glycan recovery and enrichment. 35385654 2 97 theme analytical 372:381 arg1 PAT 395:397 PAT 395:397 PAT 395:397 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 2 97 theme analytical 372:381 arg1 technology 383:392 advanced process analytical technology 355:392 advanced process analytical technology (PAT) 355:398 Federal regulatory agencies are further urging the use of advanced process analytical technology (PAT) to analyze the design space to increase the process knowledge and enable high-quality biologic production. 35385654 1 98 theme traditional 268:278 arg1 processes 286:294 traditional batch processes 268:294 traditional batch processes 268:294 The biopharmaceutical industry is transitioning toward the adoption of continuous biomanufacturing practices that are often more flexible and efficient than traditional batch processes. 35971333 2 0 theme factor 478:483 arg1 sequence 492:499 N-terminal α mating factor signal sequence 458:499 N-terminal α mating factor signal sequence from Saccharomyces cerevisiae 458:529 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 8 1 theme other 1492:1496 arg1 combinations 1498:1509 other combinations 1492:1509 other combinations 1492:1509 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein was evaluated, where N15/70A mutant showed slightly higher proliferation efficacy than other combinations. 35971333 6 2 theme native 1202:1207 arg1 control 1209:1215 native control 1202:1215 native control 1202:1215 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 7 3 gly glycosylated 1228:1239 arg1 protein 1254:1260 The fully glycosylated native hIL-3 protein 1218:1260 The fully glycosylated native hIL-3 protein 1218:1260 The fully glycosylated native hIL-3 protein showed higher thermal stability over its deglycosylated counterparts. 35971333 1 4 theme Human 138:142 arg1 cytokine 192:199 a clinically important cytokine 169:199 a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders 169:310 Human interleukin-3 (hIL-3) is a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders. 35971333 1 4 theme Human 138:142 arg1 hIL-3 159:163 hIL-3 159:163 hIL-3 159:163 Human interleukin-3 (hIL-3) is a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders. 35971333 1 4 theme Human 138:142 arg1 interleukin-3 144:156 Human interleukin-3 138:156 Human interleukin-3 (hIL-3) 138:164 Human interleukin-3 (hIL-3) is a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders. 35971333 6 5 theme 71.41 1100:1104 arg1 % 1105:1105 % 1105:1105 % 1105:1105 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 2 6 theme mating 471:476 arg1 sequence 492:499 N-terminal α mating factor signal sequence 458:499 N-terminal α mating factor signal sequence from Saccharomyces cerevisiae 458:529 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 8 7 theme N15/70A 1426:1432 arg1 mutant 1434:1439 N15/70A mutant 1426:1439 N15/70A mutant 1426:1439 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein was evaluated, where N15/70A mutant showed slightly higher proliferation efficacy than other combinations. 35971333 2 8 theme gene 334:337 arg1 cloning 317:323 The cloning 313:323 The cloning of hIL-3 gene 313:337 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 0 9 theme human 90:94 arg1 hIL-3 111:115 hIL-3 111:115 hIL-3 111:115 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 0 9 theme human 90:94 arg1 interleukin-3 96:108 recombinant human interleukin-3 78:108 recombinant human interleukin-3 (hIL-3) 78:116 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 0 10 from Effect 0:5 arg1 activity 66:73 biological activity 55:73 biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris 55:135 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 0 10 from Effect 0:5 arg1 stability 40:48 stability 40:48 stability 40:48 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 0 10 from Effect 0:5 arg1 secretion 29:37 secretion 29:37 secretion 29:37 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 5 11 theme amino 941:945 arg1 acid 947:950 non-polar alanine amino acid 923:950 non-polar alanine amino acid (Ala, A) 923:959 Asparagine at these positions was replaced with non-polar alanine amino acid (Ala, A). 35971333 1 12 theme bone 243:246 arg1 transplantation 255:269 bone marrow transplantation 243:269 bone marrow transplantation 243:269 Human interleukin-3 (hIL-3) is a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders. 35971333 0 13 theme recombinant 78:88 arg1 hIL-3 111:115 hIL-3 111:115 hIL-3 111:115 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 0 13 theme recombinant 78:88 arg1 interleukin-3 96:108 recombinant human interleukin-3 78:108 recombinant human interleukin-3 (hIL-3) 78:116 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 4 14 from Asn70 765:769 arg1 positions 727:735 The two N-linked glycosylation positions 696:735 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) 696:770 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 4 15 theme glycosylation 713:725 arg1 positions 727:735 The two N-linked glycosylation positions 696:735 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) 696:770 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 1 16 theme marrow 248:253 arg1 transplantation 255:269 bone marrow transplantation 243:269 bone marrow transplantation 243:269 Human interleukin-3 (hIL-3) is a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders. 35971333 0 17 from stability 40:48 arg1 pastoris 128:135 Pichia pastoris 121:135 Pichia pastoris 121:135 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 6 18 from secretion 1046:1054 arg1 pastoris 1066:1073 Pichia pastoris 1059:1073 Pichia pastoris 1059:1073 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 6 19 theme  lower 1106:1111 arg1 production 1113:1122 a 52.32%, 36.48%, 71.41% lower production 1082:1122 a 52.32%, 36.48%, 71.41% lower production 1082:1122 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 7 20 theme glycosylated 1228:1239 arg1 protein 1254:1260 The fully glycosylated native hIL-3 protein 1218:1260 The fully glycosylated native hIL-3 protein 1218:1260 The fully glycosylated native hIL-3 protein showed higher thermal stability over its deglycosylated counterparts. 35971333 7 21 theme hIL-3 1248:1252 arg1 protein 1254:1260 The fully glycosylated native hIL-3 protein 1218:1260 The fully glycosylated native hIL-3 protein 1218:1260 The fully glycosylated native hIL-3 protein showed higher thermal stability over its deglycosylated counterparts. 35971333 0 22 theme interleukin-3 96:108 arg1 activity 66:73 biological activity 55:73 biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris 55:135 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 0 22 theme interleukin-3 96:108 arg1 stability 40:48 stability 40:48 stability 40:48 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 0 22 theme interleukin-3 96:108 arg1 secretion 29:37 secretion 29:37 secretion 29:37 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 8 23 theme higher 1457:1462 arg1 proliferation 1464:1476 slightly higher proliferation 1448:1476 slightly higher proliferation efficacy 1448:1485 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein was evaluated, where N15/70A mutant showed slightly higher proliferation efficacy than other combinations. 35971333 6 24 link N-linked 980:987 arg1 sites 1003:1007 N-linked glycosylation sites 980:1007 N-linked glycosylation sites 980:1007 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 6 25 theme Pichia 1059:1064 arg1 pastoris 1066:1073 Pichia pastoris 1059:1073 Pichia pastoris 1059:1073 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 2 26 theme AOX1 437:440 arg1 promoter 442:449 methanol-inducible AOX1 promoter 418:449 methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae 418:529 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 0 27 from secretion 29:37 arg1 pastoris 128:135 Pichia pastoris 121:135 Pichia pastoris 121:135 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 2 28 contain having 451:456 arg2 sequence 492:499 N-terminal α mating factor signal sequence 458:499 N-terminal α mating factor signal sequence from Saccharomyces cerevisiae 458:529 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 2 28 contain having 451:456 arg1 promoter 442:449 methanol-inducible AOX1 promoter 418:449 methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae 418:529 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 3 29 theme glycosylation 568:580 arg1 pattern 582:588 glycosylation pattern 568:588 glycosylation pattern 568:588 This study investigated the role of glycosylation pattern on its molecular stability, secretion efficiency, and biological activity using the mutagenesis approach. 35971333 6 30 dep % 1089:1089 arg1 % 1097:1097 % 1097:1097 % 1097:1097 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 6 30 dep % 1089:1089 arg1 % 1105:1105 % 1105:1105 % 1105:1105 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 6 31 theme efficient 1036:1044 arg1 secretion 1046:1054 its efficient secretion 1032:1054 its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively 1032:1184 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 2 32 theme methanol-inducible 418:435 arg1 promoter 442:449 methanol-inducible AOX1 promoter 418:449 methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae 418:529 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 3 33 theme mutagenesis 674:684 arg1 approach 686:693 the mutagenesis approach 670:693 the mutagenesis approach 670:693 This study investigated the role of glycosylation pattern on its molecular stability, secretion efficiency, and biological activity using the mutagenesis approach. 35971333 3 34 theme pattern 582:588 arg1 role 560:563 the role 556:563 the role of glycosylation pattern on its molecular stability, secretion efficiency, and biological activity 556:662 This study investigated the role of glycosylation pattern on its molecular stability, secretion efficiency, and biological activity using the mutagenesis approach. 35971333 7 35 theme native 1241:1246 arg1 protein 1254:1260 The fully glycosylated native hIL-3 protein 1218:1260 The fully glycosylated native hIL-3 protein 1218:1260 The fully glycosylated native hIL-3 protein showed higher thermal stability over its deglycosylated counterparts. 35971333 8 36 theme proliferation 1464:1476 arg1 efficacy 1478:1485 slightly higher proliferation efficacy 1448:1485 slightly higher proliferation efficacy 1448:1485 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein was evaluated, where N15/70A mutant showed slightly higher proliferation efficacy than other combinations. 35971333 4 37 from Asn15 747:751 arg1 positions 727:735 The two N-linked glycosylation positions 696:735 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) 696:770 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 5 38 theme alanine 933:939 arg1 acid 947:950 non-polar alanine amino acid 923:950 non-polar alanine amino acid (Ala, A) 923:959 Asparagine at these positions was replaced with non-polar alanine amino acid (Ala, A). 35971333 4 39 theme recombinant 816:826 arg1 N70A 856:859 N70A 856:859 N70A 856:859 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 4 39 theme recombinant 816:826 arg1 N15/70A 866:872 N15/70A 866:872 N15/70A 866:872 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 4 39 theme recombinant 816:826 arg1 N15A 850:853 N15A 850:853 N15A 850:853 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 4 39 theme recombinant 816:826 arg1 variants 834:841 three recombinant hIL-3 variants 810:841 three recombinant hIL-3 variants 810:841 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 4 40 dep variants 834:841 arg1 i.e. 844:847 three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A 810:872 i.e. 844:847 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 0 41 theme N-glycosylation 10:24 arg1 Effect 0:5 Effect 0:5 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 0:136 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 6 42 located observed 1128:1135 arg1 N15A 1140:1143 N15A 1140:1143 N15A 1140:1143 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 6 42 located observed 1128:1135 arg2 production 1113:1122 a 52.32%, 36.48%, 71.41% lower production 1082:1122 a 52.32%, 36.48%, 71.41% lower production 1082:1122 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 6 42 located observed 1128:1135 arg1 N70A 1146:1149 N70A 1146:1149 N70A 1146:1149 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 6 42 located observed 1128:1135 arg1 N15/70A 1156:1162 N15/70A 1156:1162 N15/70A 1156:1162 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 5 43 theme non-polar 923:931 arg1 acid 947:950 non-polar alanine amino acid 923:950 non-polar alanine amino acid (Ala, A) 923:959 Asparagine at these positions was replaced with non-polar alanine amino acid (Ala, A). 35971333 8 44 theme N70A 1373:1376 arg1 protein 1397:1403 native, N15A, N70A, and N15/70A hIL-3 protein 1359:1403 native, N15A, N70A, and N15/70A hIL-3 protein 1359:1403 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein was evaluated, where N15/70A mutant showed slightly higher proliferation efficacy than other combinations. 35971333 4 45 theme N-linked 704:711 arg1 positions 727:735 The two N-linked glycosylation positions 696:735 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) 696:770 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 8 46 theme protein 1397:1403 arg1 activity 1347:1354 The biological activity 1332:1354 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein 1332:1403 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein was evaluated, where N15/70A mutant showed slightly higher proliferation efficacy than other combinations. 35971333 2 47 theme α 469:469 arg1 sequence 492:499 N-terminal α mating factor signal sequence 458:499 N-terminal α mating factor signal sequence from Saccharomyces cerevisiae 458:529 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 0 48 theme Pichia 121:126 arg1 pastoris 128:135 Pichia pastoris 121:135 Pichia pastoris 121:135 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 0 49 from activity 66:73 arg1 pastoris 128:135 Pichia pastoris 121:135 Pichia pastoris 121:135 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 3 50 theme molecular 597:605 arg1 stability 607:615 its molecular stability 593:615 its molecular stability 593:615 This study investigated the role of glycosylation pattern on its molecular stability, secretion efficiency, and biological activity using the mutagenesis approach. 35971333 1 51 theme important 182:190 arg1 interleukin-3 144:156 Human interleukin-3 138:156 Human interleukin-3 (hIL-3) 138:164 Human interleukin-3 (hIL-3) is a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders. 35971333 1 51 theme important 182:190 arg1 cytokine 192:199 a clinically important cytokine 169:199 a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders 169:310 Human interleukin-3 (hIL-3) is a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders. 35971333 2 52 theme N-terminal 458:467 arg1 sequence 492:499 N-terminal α mating factor signal sequence 458:499 N-terminal α mating factor signal sequence from Saccharomyces cerevisiae 458:529 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 7 53 gly deglycosylated 1303:1316 arg1 counterparts 1318:1329 its deglycosylated counterparts 1299:1329 its deglycosylated counterparts 1299:1329 The fully glycosylated native hIL-3 protein showed higher thermal stability over its deglycosylated counterparts. 35971333 6 54 theme sites 1003:1007 arg1 disadvantageous 1013:1027 disadvantageous 1013:1027 disadvantageous 1013:1027 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 6 54 theme sites 1003:1007 arg1 alteration 966:975 The alteration 962:975 The alteration of N-linked glycosylation sites 962:1007 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 8 55 theme hIL-3 1391:1395 arg1 protein 1397:1403 native, N15A, N70A, and N15/70A hIL-3 protein 1359:1403 native, N15A, N70A, and N15/70A hIL-3 protein 1359:1403 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein was evaluated, where N15/70A mutant showed slightly higher proliferation efficacy than other combinations. 35971333 1 56 theme immunological 288:300 arg1 disorders 302:310 immunological disorders 288:310 immunological disorders 288:310 Human interleukin-3 (hIL-3) is a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders. 35971333 3 57 theme biological 644:653 arg1 activity 655:662 biological activity 644:662 biological activity 644:662 This study investigated the role of glycosylation pattern on its molecular stability, secretion efficiency, and biological activity using the mutagenesis approach. 35971333 0 58 gly N-glycosylation 10:24 arg1 hIL-3 111:115 hIL-3 111:115 hIL-3 111:115 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 0 58 gly N-glycosylation 10:24 arg1 interleukin-3 96:108 recombinant human interleukin-3 78:108 recombinant human interleukin-3 (hIL-3) 78:116 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 2 59 theme hIL-3 328:332 arg1 gene 334:337 hIL-3 gene 328:337 hIL-3 gene 328:337 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 7 60 theme deglycosylated 1303:1316 arg1 counterparts 1318:1329 its deglycosylated counterparts 1299:1329 its deglycosylated counterparts 1299:1329 The fully glycosylated native hIL-3 protein showed higher thermal stability over its deglycosylated counterparts. 35971333 4 61 theme hIL-3 828:832 arg1 N70A 856:859 N70A 856:859 N70A 856:859 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 4 61 theme hIL-3 828:832 arg1 N15/70A 866:872 N15/70A 866:872 N15/70A 866:872 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 4 61 theme hIL-3 828:832 arg1 N15A 850:853 N15A 850:853 N15A 850:853 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 4 61 theme hIL-3 828:832 arg1 variants 834:841 three recombinant hIL-3 variants 810:841 three recombinant hIL-3 variants 810:841 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 6 62 theme % 1089:1089 arg1  lower 1106:1111 a 52.32%, 36.48%, 71.41% lower 1082:1111 a 52.32%, 36.48%, 71.41% lower production 1082:1122 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 3 63 from role 560:563 arg1 activity 655:662 biological activity 644:662 biological activity 644:662 This study investigated the role of glycosylation pattern on its molecular stability, secretion efficiency, and biological activity using the mutagenesis approach. 35971333 3 63 from role 560:563 arg1 stability 607:615 its molecular stability 593:615 its molecular stability 593:615 This study investigated the role of glycosylation pattern on its molecular stability, secretion efficiency, and biological activity using the mutagenesis approach. 35971333 3 63 from role 560:563 arg1 efficiency 628:637 secretion efficiency 618:637 secretion efficiency 618:637 This study investigated the role of glycosylation pattern on its molecular stability, secretion efficiency, and biological activity using the mutagenesis approach. 35971333 5 64 from positions 895:903 arg1 Asparagine 875:884 Asparagine 875:884 Asparagine at these positions 875:903 Asparagine at these positions was replaced with non-polar alanine amino acid (Ala, A). 35971333 8 65 theme N15/70A 1383:1389 arg1 protein 1397:1403 native, N15A, N70A, and N15/70A hIL-3 protein 1359:1403 native, N15A, N70A, and N15/70A hIL-3 protein 1359:1403 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein was evaluated, where N15/70A mutant showed slightly higher proliferation efficacy than other combinations. 35971333 4 66 link N-linked 704:711 arg1 positions 727:735 The two N-linked glycosylation positions 696:735 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) 696:770 The two N-linked glycosylation positions at N15th (Asn15) and N70th (Asn70) were sequentially mutated to generate three recombinant hIL-3 variants, i.e., N15A, N70A, and N15/70A. 35971333 7 67 theme higher 1269:1274 arg1 stability 1284:1292 higher thermal stability 1269:1292 higher thermal stability 1269:1292 The fully glycosylated native hIL-3 protein showed higher thermal stability over its deglycosylated counterparts. 35971333 6 68 theme N-linked 980:987 arg1 sites 1003:1007 N-linked glycosylation sites 980:1007 N-linked glycosylation sites 980:1007 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 5 69 dep acid 947:950 arg1 A 958:958 A 958:958 A 958:958 Asparagine at these positions was replaced with non-polar alanine amino acid (Ala, A). 35971333 5 69 dep acid 947:950 arg1 Ala 953:955 Ala 953:955 Ala 953:955 Asparagine at these positions was replaced with non-polar alanine amino acid (Ala, A). 35971333 6 70 theme glycosylation 989:1001 arg1 sites 1003:1007 N-linked glycosylation sites 980:1007 N-linked glycosylation sites 980:1007 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 7 71 theme thermal 1276:1282 arg1 stability 1284:1292 higher thermal stability 1269:1292 higher thermal stability 1269:1292 The fully glycosylated native hIL-3 protein showed higher thermal stability over its deglycosylated counterparts. 35971333 6 72 dep N15A 1140:1143 arg1 mutants 1164:1170 mutants 1164:1170 mutants 1164:1170 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 6 73 theme 52.32 1084:1088 arg1 % 1089:1089 % 1089:1089 % 1089:1089 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 0 74 theme biological 55:64 arg1 activity 66:73 biological activity 55:73 biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris 55:135 Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human interleukin-3 (hIL-3) in Pichia pastoris. 35971333 2 75 from cerevisiae 520:529 arg1 sequence 492:499 N-terminal α mating factor signal sequence 458:499 N-terminal α mating factor signal sequence from Saccharomyces cerevisiae 458:529 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 8 76 theme N15A 1367:1370 arg1 protein 1397:1403 native, N15A, N70A, and N15/70A hIL-3 protein 1359:1403 native, N15A, N70A, and N15/70A hIL-3 protein 1359:1403 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein was evaluated, where N15/70A mutant showed slightly higher proliferation efficacy than other combinations. 35971333 6 77 gly glycosylation 989:1001 arg2 sites 1003:1007 N-linked glycosylation sites 980:1007 N-linked glycosylation sites 980:1007 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 8 78 theme biological 1336:1345 arg1 activity 1347:1354 The biological activity 1332:1354 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein 1332:1403 The biological activity of native, N15A, N70A, and N15/70A hIL-3 protein was evaluated, where N15/70A mutant showed slightly higher proliferation efficacy than other combinations. 35971333 2 79 theme signal 485:490 arg1 sequence 492:499 N-terminal α mating factor signal sequence 458:499 N-terminal α mating factor signal sequence from Saccharomyces cerevisiae 458:529 The cloning of hIL-3 gene was previously reported by our group, where its expression was optimized under methanol-inducible AOX1 promoter having N-terminal α mating factor signal sequence from Saccharomyces cerevisiae. 35971333 6 80 theme 36.48 1092:1096 arg1 % 1097:1097 % 1097:1097 % 1097:1097 The alteration of N-linked glycosylation sites was disadvantageous to its efficient secretion in Pichia pastoris, where a 52.32%, 36.48%, 71.41% lower production was observed in N15A, N70A, and N15/70A mutants, respectively, as compared to native control. 35971333 3 81 theme secretion 618:626 arg1 efficiency 628:637 secretion efficiency 618:637 secretion efficiency 618:637 This study investigated the role of glycosylation pattern on its molecular stability, secretion efficiency, and biological activity using the mutagenesis approach. 35971333 1 82 theme hematological 215:227 arg1 malignancies 229:240 hematological malignancies 215:240 hematological malignancies 215:240 Human interleukin-3 (hIL-3) is a clinically important cytokine used to treat hematological malignancies, bone marrow transplantation, cytopenias, and immunological disorders. 35401511 6 0 from EN 962:963 arg1 prominent 949:957 prominent 949:957 prominent 949:957 Strikingly, agalactosylated glycan residues were more prominent in EN, whereas sialylation and bisecting GlcNac correlated with asymptomatic infections. 35401511 4 1 theme total 762:766 arg1 IgG 768:770 total IgG 762:770 total IgG purified from endemic normals (EN) 762:805 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 7 2 theme IgG 1184:1186 arg1 expressions 1156:1166 significantly lower expressions 1136:1166 significantly lower expressions of afucosylated IgG 1136:1186 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 6 3 theme agalactosylated 907:921 arg1 residues 930:937 agalactosylated glycan residues 907:937 agalactosylated glycan residues 907:937 Strikingly, agalactosylated glycan residues were more prominent in EN, whereas sialylation and bisecting GlcNac correlated with asymptomatic infections. 35401511 1 4 theme chronic 283:289 arg1 pathology 291:299 chronic pathology 283:299 chronic pathology (CP) 283:304 Lymphatic filariasis presents a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis. 35401511 1 4 theme chronic 283:289 arg1 CP 302:303 CP 302:303 CP 302:303 Lymphatic filariasis presents a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis. 35401511 7 5 theme residues 1126:1133 arg1 levels 1104:1109 high levels 1099:1109 high levels of fucosylated residues 1099:1133 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 1 6 theme complex 187:193 arg1 spectrum 195:202 a complex spectrum 185:202 a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis 185:344 Lymphatic filariasis presents a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis. 35401511 10 7 theme infectious 1776:1785 arg1 diseases 1787:1794 infectious diseases 1776:1794 infectious diseases 1776:1794 These findings highlight the link between N-glycosylation and the physiopathology of lymphatic filariasis and open new research avenues for next-generation therapeutic formulations against infectious diseases. 35401511 4 8 theme total 616:620 arg1 patterns 642:649 total IgG-N-glycosylation patterns 616:649 total IgG-N-glycosylation patterns 616:649 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 8 9 link N-linked 1265:1272 arg1 profiles 1285:1292 distinct N-linked IgG glycan profiles 1256:1292 distinct N-linked IgG glycan profiles in EN, MF+, and CP 1256:1311 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 0 10 theme Asymptomatic 100:111 arg1 Infections 113:122 Asymptomatic Infections 100:122 Asymptomatic Infections 100:122 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 7 11 theme afucosylated 1171:1182 arg1 IgG 1184:1186 afucosylated IgG 1171:1186 afucosylated IgG 1171:1186 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 7 12 theme MF+ 1201:1203 arg1 individuals 1205:1215 MF+ individuals 1201:1215 MF+ individuals 1201:1215 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 4 13 theme UPLC-FLD/ESI-MS 711:725 arg1 comparison 727:736 UPLC-FLD/ESI-MS comparison 711:736 UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN) 711:805 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 0 14 theme Human 127:131 arg1 Filariasis 143:152 Human Lymphatic Filariasis 127:152 Human Lymphatic Filariasis 127:152 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 7 15 theme lower 1150:1154 arg1 expressions 1156:1166 significantly lower expressions 1136:1166 significantly lower expressions of afucosylated IgG 1136:1186 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 10 16 theme therapeutic 1743:1753 arg1 formulations 1755:1766 next-generation therapeutic formulations 1727:1766 next-generation therapeutic formulations against infectious diseases 1727:1794 These findings highlight the link between N-glycosylation and the physiopathology of lymphatic filariasis and open new research avenues for next-generation therapeutic formulations against infectious diseases. 35401511 8 17 theme chronic 1386:1392 arg1 pathology 1394:1402 chronic pathology 1386:1402 chronic pathology 1386:1402 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 2 18 theme infections 421:430 arg1 physiopathology 393:407 the physiopathology 389:407 the physiopathology of filarial infections and antibody properties 389:454 Emerging evidence suggests a link between the physiopathology of filarial infections and antibody properties. 35401511 2 19 theme antibody 436:443 arg1 properties 445:454 antibody properties 436:454 antibody properties 436:454 Emerging evidence suggests a link between the physiopathology of filarial infections and antibody properties. 35401511 6 20 theme asymptomatic 1023:1034 arg1 infections 1036:1045 asymptomatic infections 1023:1045 asymptomatic infections 1023:1045 Strikingly, agalactosylated glycan residues were more prominent in EN, whereas sialylation and bisecting GlcNac correlated with asymptomatic infections. 35401511 6 21 theme glycan 923:928 arg1 residues 930:937 agalactosylated glycan residues 907:937 agalactosylated glycan residues 907:937 Strikingly, agalactosylated glycan residues were more prominent in EN, whereas sialylation and bisecting GlcNac correlated with asymptomatic infections. 35401511 4 22 theme IgG-N-glycosylation 622:640 arg1 patterns 642:649 total IgG-N-glycosylation patterns 616:649 total IgG-N-glycosylation patterns 616:649 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 9 23 theme immune 1553:1558 arg1 tolerance 1560:1568 immune tolerance 1553:1568 immune tolerance to the parasite 1553:1584 The results also indicate a role for sialylation, fucosylation, and bisecting GlcNac in immune tolerance to the parasite. 35401511 4 24 theme CP 817:818 arg1 patients 820:827 CP patients 817:827 CP patients 817:827 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 8 25 theme glycan 1278:1283 arg1 profiles 1285:1292 distinct N-linked IgG glycan profiles 1256:1292 distinct N-linked IgG glycan profiles in EN, MF+, and CP 1256:1311 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 0 26 theme N-Linked 9:16 arg1 Glycosylation 35:47 N-Linked Immunoglobulin G Glycosylation 9:47 Distinct N-Linked Immunoglobulin G Glycosylation Patterns 0:56 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 6 27 theme bisecting 990:998 arg1 GlcNac 1000:1005 bisecting GlcNac 990:1005 bisecting GlcNac 990:1005 Strikingly, agalactosylated glycan residues were more prominent in EN, whereas sialylation and bisecting GlcNac correlated with asymptomatic infections. 35401511 6 28 from prominent 949:957 arg1 EN 962:963 EN 962:963 EN 962:963 Strikingly, agalactosylated glycan residues were more prominent in EN, whereas sialylation and bisecting GlcNac correlated with asymptomatic infections. 35401511 2 29 theme Emerging 347:354 arg1 evidence 356:363 Emerging evidence 347:363 Emerging evidence 347:363 Emerging evidence suggests a link between the physiopathology of filarial infections and antibody properties. 35401511 1 30 theme clinical 207:214 arg1 manifestations 216:229 clinical manifestations 207:229 clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis 207:344 Lymphatic filariasis presents a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis. 35401511 0 31 theme Distinct 0:7 arg1 Patterns 49:56 Distinct N-Linked Immunoglobulin G Glycosylation Patterns 0:56 Distinct N-Linked Immunoglobulin G Glycosylation Patterns 0:56 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 2 32 theme filarial 412:419 arg1 infections 421:430 filarial infections 412:430 filarial infections 412:430 Emerging evidence suggests a link between the physiopathology of filarial infections and antibody properties. 35401511 0 33 theme G 33:33 arg1 Glycosylation 35:47 N-Linked Immunoglobulin G Glycosylation 9:47 Distinct N-Linked Immunoglobulin G Glycosylation Patterns 0:56 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 7 34 theme fucosylated 1114:1124 arg1 residues 1126:1133 fucosylated residues 1114:1133 fucosylated residues 1114:1133 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 10 35 theme new 1702:1704 arg1 avenues 1715:1721 new research avenues 1702:1721 new research avenues for next-generation therapeutic formulations against infectious diseases 1702:1794 These findings highlight the link between N-glycosylation and the physiopathology of lymphatic filariasis and open new research avenues for next-generation therapeutic formulations against infectious diseases. 35401511 8 36 theme distinct 1256:1263 arg1 profiles 1285:1292 distinct N-linked IgG glycan profiles 1256:1292 distinct N-linked IgG glycan profiles in EN, MF+, and CP 1256:1311 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 3 37 theme key 515:517 arg1 role 519:522 a key role 513:522 a key role 513:522 Post-translational glycosylation has been shown to play a key role in the modulation of antibodies' effector functions. 35401511 0 38 theme Immunoglobulin 18:31 arg1 Glycosylation 35:47 N-Linked Immunoglobulin G Glycosylation 9:47 Distinct N-Linked Immunoglobulin G Glycosylation Patterns 0:56 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 0 39 theme Lymphatic 133:141 arg1 Filariasis 143:152 Human Lymphatic Filariasis 127:152 Human Lymphatic Filariasis 127:152 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 4 40 theme IgG 768:770 arg1 profiles 750:757 N-glycan profiles 741:757 N-glycan profiles of total IgG purified from endemic normals (EN) 741:805 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 4 41 theme lymphatic 684:692 arg1 filariasis 694:703 human lymphatic filariasis 678:703 human lymphatic filariasis 678:703 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 3 42 theme Post-translational 457:474 arg1 glycosylation 476:488 Post-translational glycosylation 457:488 Post-translational glycosylation 457:488 Post-translational glycosylation has been shown to play a key role in the modulation of antibodies' effector functions. 35401511 4 43 theme profiles 750:757 arg1 MF+ 808:810 MF+ 808:810 MF+ 808:810 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 4 43 theme profiles 750:757 arg1 comparison 727:736 UPLC-FLD/ESI-MS comparison 711:736 UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN) 711:805 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 4 43 theme profiles 750:757 arg1 patients 820:827 CP patients 817:827 CP patients 817:827 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 9 44 theme bisecting 1533:1541 arg1 GlcNac 1543:1548 bisecting GlcNac 1533:1548 bisecting GlcNac 1533:1548 The results also indicate a role for sialylation, fucosylation, and bisecting GlcNac in immune tolerance to the parasite. 35401511 0 45 from Pathology 86:94 arg1 Filariasis 143:152 Human Lymphatic Filariasis 127:152 Human Lymphatic Filariasis 127:152 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 1 46 theme manifestations 216:229 arg1 spectrum 195:202 a complex spectrum 185:202 a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis 185:344 Lymphatic filariasis presents a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis. 35401511 1 47 theme asymptomatic 244:255 arg1 MF+ 275:277 MF+ 275:277 MF+ 275:277 Lymphatic filariasis presents a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis. 35401511 1 47 theme asymptomatic 244:255 arg1 microfilariaemic 257:272 asymptomatic microfilariaemic 244:272 asymptomatic microfilariaemic (MF+) 244:278 Lymphatic filariasis presents a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis. 35401511 0 48 theme Glycosylation 35:47 arg1 Patterns 49:56 Distinct N-Linked Immunoglobulin G Glycosylation Patterns 0:56 Distinct N-Linked Immunoglobulin G Glycosylation Patterns 0:56 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 10 49 theme filariasis 1682:1691 arg1 physiopathology 1653:1667 the physiopathology 1649:1667 the physiopathology of lymphatic filariasis 1649:1691 These findings highlight the link between N-glycosylation and the physiopathology of lymphatic filariasis and open new research avenues for next-generation therapeutic formulations against infectious diseases. 35401511 10 49 theme filariasis 1682:1691 arg1 link 1616:1619 the link 1612:1619 the link between N-glycosylation 1612:1643 These findings highlight the link between N-glycosylation and the physiopathology of lymphatic filariasis and open new research avenues for next-generation therapeutic formulations against infectious diseases. 35401511 8 50 theme IgG 1330:1332 arg1 galactosylation 1334:1348 IgG galactosylation 1330:1348 IgG galactosylation 1330:1348 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 2 51 theme properties 445:454 arg1 physiopathology 393:407 the physiopathology 389:407 the physiopathology of filarial infections and antibody properties 389:454 Emerging evidence suggests a link between the physiopathology of filarial infections and antibody properties. 35401511 8 52 theme IgG 1274:1276 arg1 profiles 1285:1292 distinct N-linked IgG glycan profiles 1256:1292 distinct N-linked IgG glycan profiles in EN, MF+, and CP 1256:1311 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 4 53 theme endemic 786:792 arg1 EN 803:804 EN 803:804 EN 803:804 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 4 53 theme endemic 786:792 arg1 normals 794:800 endemic normals 786:800 endemic normals (EN) 786:805 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 8 54 theme N-linked 1265:1272 arg1 profiles 1285:1292 distinct N-linked IgG glycan profiles 1256:1292 distinct N-linked IgG glycan profiles in EN, MF+, and CP 1256:1311 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 7 55 theme high 1099:1102 arg1 levels 1104:1109 high levels 1099:1109 high levels of fucosylated residues 1099:1133 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 10 56 theme next-generation 1727:1741 arg1 formulations 1755:1766 next-generation therapeutic formulations 1727:1766 next-generation therapeutic formulations against infectious diseases 1727:1794 These findings highlight the link between N-glycosylation and the physiopathology of lymphatic filariasis and open new research avenues for next-generation therapeutic formulations against infectious diseases. 35401511 8 57 theme putative 1446:1453 arg1 immunity 1455:1462 putative immunity 1446:1462 putative immunity 1446:1462 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 8 58 from profiles 1285:1292 arg1 MF+ 1301:1303 MF+ 1301:1303 MF+ 1301:1303 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 8 58 from profiles 1285:1292 arg1 CP 1310:1311 CP 1310:1311 CP 1310:1311 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 8 58 from profiles 1285:1292 arg1 EN 1297:1298 EN 1297:1298 EN 1297:1298 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 4 59 theme N-glycan 741:748 arg1 profiles 750:757 N-glycan profiles 741:757 N-glycan profiles of total IgG purified from endemic normals (EN) 741:805 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 7 60 theme clinical 1073:1080 arg1 groups 1082:1087 all three clinical groups 1063:1087 all three clinical groups 1063:1087 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 5 61 attach released 864:871 arg2 glycans 856:862 19 glycans 853:862 19 glycans released from all IgG samples 853:892 We detected a total of 19 glycans released from all IgG samples. 35401511 5 61 attach released 864:871 arg1 samples 886:892 all IgG samples 878:892 all IgG samples 878:892 We detected a total of 19 glycans released from all IgG samples. 35401511 8 62 dep associated 1370:1379 arg1 whereas 1405:1411 whereas 1405:1411 whereas 1405:1411 Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. 35401511 7 63 gly fucosylated 1114:1124 arg1 residues 1126:1133 fucosylated residues 1114:1133 fucosylated residues 1114:1133 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 0 64 from Infections 113:122 arg1 Filariasis 143:152 Human Lymphatic Filariasis 127:152 Human Lymphatic Filariasis 127:152 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 9 65 from role 1493:1496 arg1 tolerance 1560:1568 immune tolerance 1553:1568 immune tolerance to the parasite 1553:1584 The results also indicate a role for sialylation, fucosylation, and bisecting GlcNac in immune tolerance to the parasite. 35401511 1 66 theme Lymphatic 155:163 arg1 filariasis 165:174 Lymphatic filariasis 155:174 Lymphatic filariasis 155:174 Lymphatic filariasis presents a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis. 35401511 7 67 gly afucosylated 1171:1182 arg1 IgG 1184:1186 afucosylated IgG 1171:1186 afucosylated IgG 1171:1186 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 7 68 from groups 1082:1087 arg1 IgG 1054:1056 IgG 1054:1056 IgG from all three clinical groups 1054:1087 While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. 35401511 0 69 theme Chronic 78:84 arg1 Pathology 86:94 Chronic Pathology 78:94 Chronic Pathology 78:94 Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. 35401511 5 70 theme IgG 882:884 arg1 samples 886:892 all IgG samples 878:892 all IgG samples 878:892 We detected a total of 19 glycans released from all IgG samples. 35401511 4 71 theme filariasis 694:703 arg1 physiopathology 659:673 the physiopathology 655:673 the physiopathology of human lymphatic filariasis 655:703 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 4 71 theme filariasis 694:703 arg1 link 603:606 the link 599:606 the link between total IgG-N-glycosylation patterns 599:649 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 3 72 theme effector 557:564 arg1 functions 566:574 antibodies' effector functions 545:574 antibodies' effector functions 545:574 Post-translational glycosylation has been shown to play a key role in the modulation of antibodies' effector functions. 35401511 10 73 theme research 1706:1713 arg1 avenues 1715:1721 new research avenues 1702:1721 new research avenues for next-generation therapeutic formulations against infectious diseases 1702:1794 These findings highlight the link between N-glycosylation and the physiopathology of lymphatic filariasis and open new research avenues for next-generation therapeutic formulations against infectious diseases. 35401511 4 74 theme human 678:682 arg1 filariasis 694:703 human lymphatic filariasis 678:703 human lymphatic filariasis 678:703 Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. 35401511 10 75 theme lymphatic 1672:1680 arg1 filariasis 1682:1691 lymphatic filariasis 1672:1691 lymphatic filariasis 1672:1691 These findings highlight the link between N-glycosylation and the physiopathology of lymphatic filariasis and open new research avenues for next-generation therapeutic formulations against infectious diseases. 35401511 5 76 theme glycans 856:862 arg1 total 844:848 a total 842:848 a total of 19 glycans released from all IgG samples 842:892 We detected a total of 19 glycans released from all IgG samples. 35401511 3 77 theme functions 566:574 arg1 modulation 531:540 the modulation 527:540 the modulation of antibodies' effector functions 527:574 Post-translational glycosylation has been shown to play a key role in the modulation of antibodies' effector functions. 37162453 4 0 theme rough 598:602 arg1 surfaces 604:611 rough surfaces 598:611 rough surfaces 598:611 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 5 1 theme persisting 795:804 arg1 adhesion 806:813 strong, instant, and persisting adhesion 774:813 strong, instant, and persisting adhesion to various substrates with different surface roughness 774:868 Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. 37162453 9 2 theme petroleum-based 1368:1382 arg1 gels 1384:1387 petroleum-based gels 1368:1387 petroleum-based gels 1368:1387 Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions. 37162453 1 3 theme flexible 177:184 arg1 materials 192:200 flexible smart materials 177:200 flexible smart materials 177:200 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 9 4 theme bio-based 1335:1343 arg1 gels 1354:1357 most bio-based adhesive gels 1330:1357 most bio-based adhesive gels 1330:1357 Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions. 37162453 4 5 dep microgels 699:707 arg1 size 718:721 average size 710:721 average size = 1.25 ± 0.03 µm 710:738 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 3 6 theme abundant 406:413 arg1 compounds 425:433 the most abundant bio-based compounds 397:433 the most abundant bio-based compounds 397:433 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 2 7 theme daunting 312:319 arg1 challenge 321:329 a daunting challenge 310:329 a daunting challenge for adhesive gels 310:347 Combining high toughness and strong, persisting repeatable adhesion has always been a daunting challenge for adhesive gels. 37162453 8 8 theme adhesive 1246:1253 arg1 strength 1255:1262 the adhesive strength 1242:1262 the adhesive strength 1242:1262 After five cycles (re-lap after detaching), the adhesive strength still remains above 200 KPa. 37162453 6 9 theme resulting 957:965 arg1 membranes 976:984 resulting microgel membranes 957:984 resulting microgel membranes 957:984 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 5 10 with substrates 826:835 arg1 roughness 860:868 different surface roughness 842:868 different surface roughness 842:868 Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. 37162453 3 11 contain possess 443:449 arg2 adhesion 489:496 weak interfacial adhesion 472:496 weak interfacial adhesion 472:496 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 3 11 contain possess 443:449 arg1 gels 364:367 bulk gels 359:367 bulk gels based on polysaccharides as the most abundant bio-based compounds 359:433 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 3 11 contain possess 443:449 arg2 toughness 458:466 a high toughness 451:466 a high toughness 451:466 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 4 12 dep = 723:723 arg1 1.25 ± 0.03 µm 725:738 1.25 ± 0.03 µm 725:738 1.25 ± 0.03 µm 725:738 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 6 13 theme 73.8 ± 9.3 KJ m-3 1053:1069 arg1 strength 1007:1014 high tensile strength 994:1014 high tensile strength 994:1014 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 6 13 theme 73.8 ± 9.3 KJ m-3 1053:1069 arg1 toughness 1020:1028 toughness 1020:1028 toughness 1020:1028 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 5 14 theme strong 774:779 arg1 adhesion 806:813 strong, instant, and persisting adhesion 774:813 strong, instant, and persisting adhesion to various substrates with different surface roughness 774:868 Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. 37162453 3 15 theme strong 509:514 arg1 potential 526:534 the strong hydration potential 505:534 the strong hydration potential 505:534 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 4 16 theme cross-linked 652:663 arg1 microgels 699:707 loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels 633:707 loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm) 633:739 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 1 17 theme smart 186:190 arg1 materials 192:200 flexible smart materials 177:200 flexible smart materials 177:200 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 9 18 theme molecular 1421:1429 arg1 interactions 1459:1470 synergistic molecular and microscaled topological interactions 1409:1470 synergistic molecular and microscaled topological interactions 1409:1470 Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions. 37162453 9 19 theme adhesive 1299:1306 arg1 properties 1308:1317 Their adhesive properties 1293:1317 Their adhesive properties 1293:1317 Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions. 37162453 1 20 theme biobased 91:98 arg1 materials 112:120 biobased sustainable materials 91:120 biobased sustainable materials 91:120 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 9 21 theme adhesive 1345:1352 arg1 gels 1354:1357 most bio-based adhesive gels 1330:1357 most bio-based adhesive gels 1330:1357 Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions. 37162453 4 22 theme cDHPC 692:696 arg1 microgels 699:707 loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels 633:707 loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm) 633:739 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 0 23 theme Strong 15:20 arg1 Adhesion 22:29 Scale-Spanning Strong Adhesion 0:29 Scale-Spanning Strong Adhesion 0:29 Scale-Spanning Strong Adhesion Using Cellulose-Based Microgels. 37162453 4 24 theme microgel 574:581 arg1 membranes 583:591 highly tough microgel membranes 561:591 highly tough microgel membranes with rough surfaces 561:611 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 4 25 theme tough 568:572 arg1 membranes 583:591 highly tough microgel membranes 561:591 highly tough microgel membranes with rough surfaces 561:611 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 1 26 theme sustainable 100:110 arg1 materials 112:120 biobased sustainable materials 91:120 biobased sustainable materials 91:120 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 9 27 theme synergistic 1409:1419 arg1 interactions 1459:1470 synergistic molecular and microscaled topological interactions 1409:1470 synergistic molecular and microscaled topological interactions 1409:1470 Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions. 37162453 0 28 theme Scale-Spanning 0:13 arg1 Adhesion 22:29 Scale-Spanning Strong Adhesion 0:29 Scale-Spanning Strong Adhesion 0:29 Scale-Spanning Strong Adhesion Using Cellulose-Based Microgels. 37162453 1 29 attach derived 78:84 arg2 gels 73:76 Adhesive gels 64:76 Adhesive gels derived from biobased sustainable materials 64:120 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 1 29 attach derived 78:84 arg1 materials 112:120 biobased sustainable materials 91:120 biobased sustainable materials 91:120 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 6 30 theme high 994:997 arg1 strength 1007:1014 high tensile strength 994:1014 high tensile strength 994:1014 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 2 31 theme adhesive 335:342 arg1 gels 344:347 adhesive gels 335:347 adhesive gels 335:347 Combining high toughness and strong, persisting repeatable adhesion has always been a daunting challenge for adhesive gels. 37162453 1 32 theme biomedicine 206:216 arg1 fields 218:223 biomedicine fields 206:223 biomedicine fields 206:223 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 5 33 theme surface 852:858 arg1 roughness 860:868 different surface roughness 842:868 different surface roughness 842:868 Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. 37162453 5 34 theme different 842:850 arg1 roughness 860:868 different surface roughness 842:868 different surface roughness 842:868 Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. 37162453 5 35 theme various 818:824 arg1 substrates 826:835 various substrates 818:835 various substrates with different surface roughness 818:868 Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. 37162453 4 36 theme dihydroxypropyl 665:679 arg1 microgels 699:707 loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels 633:707 loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm) 633:739 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 8 37 dep cycles 1209:1214 arg1 re-lap 1217:1222 re-lap 1217:1222 re-lap 1217:1222 After five cycles (re-lap after detaching), the adhesive strength still remains above 200 KPa. 37162453 4 38 theme membranes 583:591 arg1 kind 553:556 a novel kind 545:556 a novel kind of highly tough microgel membranes with rough surfaces 545:611 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 9 39 theme microscaled 1435:1445 arg1 interactions 1459:1470 synergistic molecular and microscaled topological interactions 1409:1470 synergistic molecular and microscaled topological interactions 1409:1470 Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions. 37162453 4 40 theme = 723:723 arg1 size 718:721 average size 710:721 average size = 1.25 ± 0.03 µm 710:738 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 3 41 theme due 498:500 arg1 toughness 458:466 a high toughness 451:466 a high toughness 451:466 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 3 42 theme hydration 516:524 arg1 potential 526:534 the strong hydration potential 505:534 the strong hydration potential 505:534 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 5 43 theme Such 742:745 arg1 membranes 756:764 Such microgel membranes 742:764 Such microgel membranes 742:764 Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. 37162453 6 44 theme physical 914:921 arg1 interactions 923:934 multiple physical interactions 905:934 multiple physical interactions within microgels and resulting microgel membranes 905:984 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 4 45 theme cellulose 681:689 arg1 microgels 699:707 loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels 633:707 loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm) 633:739 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 3 46 theme high 453:456 arg1 toughness 458:466 a high toughness 451:466 a high toughness 451:466 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 3 47 theme weak 472:475 arg1 adhesion 489:496 weak interfacial adhesion 472:496 weak interfacial adhesion 472:496 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 0 48 theme Cellulose-Based 37:51 arg1 Microgels 53:61 Cellulose-Based Microgels 37:61 Cellulose-Based Microgels 37:61 Scale-Spanning Strong Adhesion Using Cellulose-Based Microgels. 37162453 4 49 theme novel 547:551 arg1 kind 553:556 a novel kind 545:556 a novel kind of highly tough microgel membranes with rough surfaces 545:611 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 5 50 theme microgel 747:754 arg1 membranes 756:764 Such microgel membranes 742:764 Such microgel membranes 742:764 Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. 37162453 6 51 theme multiple 905:912 arg1 interactions 923:934 multiple physical interactions 905:934 multiple physical interactions within microgels and resulting microgel membranes 905:984 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 2 52 theme strong 255:260 arg1 adhesion 285:292 strong, persisting repeatable adhesion 255:292 strong, persisting repeatable adhesion 255:292 Combining high toughness and strong, persisting repeatable adhesion has always been a daunting challenge for adhesive gels. 37162453 7 53 theme adhesive 1099:1106 arg1 strength 1108:1115 The maximum adhesive strength 1087:1115 The maximum adhesive strength 1087:1115 The maximum adhesive strength and debonding work exceed 320 ± 0.50 KPa and 160.97 ± 0.20 J m-2 , respectively. 37162453 2 54 dep strong 255:260 arg1 persisting 263:272 persisting 263:272 persisting 263:272 Combining high toughness and strong, persisting repeatable adhesion has always been a daunting challenge for adhesive gels. 37162453 3 55 theme bio-based 415:423 arg1 compounds 425:433 the most abundant bio-based compounds 397:433 the most abundant bio-based compounds 397:433 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 1 56 contain have 122:125 arg1 gels 73:76 Adhesive gels 64:76 Adhesive gels derived from biobased sustainable materials 64:120 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 1 56 contain have 122:125 arg2 prospects 155:163 extremely broad application prospects 127:163 extremely broad application prospects 127:163 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 6 57 theme 0.23 ± 0.03 MPa 1033:1047 arg1 strength 1007:1014 high tensile strength 994:1014 high tensile strength 994:1014 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 6 57 theme 0.23 ± 0.03 MPa 1033:1047 arg1 toughness 1020:1028 toughness 1020:1028 toughness 1020:1028 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 1 58 theme broad 137:141 arg1 prospects 155:163 extremely broad application prospects 127:163 extremely broad application prospects 127:163 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 6 59 theme microgel 967:974 arg1 membranes 976:984 resulting microgel membranes 957:984 resulting microgel membranes 957:984 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 6 60 theme tensile 999:1005 arg1 strength 1007:1014 high tensile strength 994:1014 high tensile strength 994:1014 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 2 61 theme high 236:239 arg1 toughness 241:249 high toughness 236:249 high toughness 236:249 Combining high toughness and strong, persisting repeatable adhesion has always been a daunting challenge for adhesive gels. 37162453 1 62 theme application 143:153 arg1 prospects 155:163 extremely broad application prospects 127:163 extremely broad application prospects 127:163 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 4 63 link cross-linked 652:663 arg1 microgels 699:707 loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels 633:707 loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm) 633:739 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 6 64 theme chemical 878:885 arg1 cross-linking 887:899 Slight chemical cross-linking 871:899 Slight chemical cross-linking 871:899 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 7 65 theme maximum 1091:1097 arg1 strength 1108:1115 The maximum adhesive strength 1087:1115 The maximum adhesive strength 1087:1115 The maximum adhesive strength and debonding work exceed 320 ± 0.50 KPa and 160.97 ± 0.20 J m-2 , respectively. 37162453 6 66 theme Slight 871:876 arg1 cross-linking 887:899 Slight chemical cross-linking 871:899 Slight chemical cross-linking 871:899 Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. 37162453 4 67 with membranes 583:591 arg1 surfaces 604:611 rough surfaces 598:611 rough surfaces 598:611 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 37162453 9 68 theme topological 1447:1457 arg1 interactions 1459:1470 synergistic molecular and microscaled topological interactions 1409:1470 synergistic molecular and microscaled topological interactions 1409:1470 Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions. 37162453 5 69 theme instant 782:788 arg1 adhesion 806:813 strong, instant, and persisting adhesion 774:813 strong, instant, and persisting adhesion to various substrates with different surface roughness 774:868 Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. 37162453 3 70 theme interfacial 477:487 arg1 adhesion 489:496 weak interfacial adhesion 472:496 weak interfacial adhesion 472:496 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 2 71 theme repeatable 274:283 arg1 adhesion 285:292 strong, persisting repeatable adhesion 255:292 strong, persisting repeatable adhesion 255:292 Combining high toughness and strong, persisting repeatable adhesion has always been a daunting challenge for adhesive gels. 37162453 3 72 theme bulk 359:362 arg1 gels 364:367 bulk gels 359:367 bulk gels based on polysaccharides as the most abundant bio-based compounds 359:433 However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. 37162453 1 73 theme Adhesive 64:71 arg1 gels 73:76 Adhesive gels 64:76 Adhesive gels derived from biobased sustainable materials 64:120 Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. 37162453 4 74 theme average 710:716 arg1 size 718:721 average size 710:721 average size = 1.25 ± 0.03 µm 710:738 Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). 35240313 12 0 theme only 1874:1877 arg1 compound 1879:1886 the only compound 1870:1886 the only compound 1870:1886 Safranal was the only compound demonstrated the anti-proliferation effect. 35240313 11 1 theme cell 1725:1728 arg1 viability 1730:1738 the cell viability 1721:1738 the cell viability of MDA-MB-231 cell lines 1721:1763 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 13 2 theme treated 2041:2047 arg1 lines 2054:2058 treated cell lines 2041:2058 treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2041:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 3 theme -based 2208:2213 arg1 strategy 2292:2299 a strategy 2290:2299 a strategy to follow the more detailed mechanisms of safranal effect 2290:2357 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 3 theme -based 2208:2213 arg1 enrichment 2215:2224 the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment 2024:2224 the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides 2024:2261 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 4 theme lines 2054:2058 arg1 set 2034:2036 three set 2028:2036 three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2028:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 4 theme lines 2054:2058 arg1 lines 2054:2058 treated cell lines 2041:2058 treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2041:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 5 theme N-linked 2240:2247 arg1 glycopeptides 2249:2261 sialylated N-linked glycopeptides 2229:2261 sialylated N-linked glycopeptides 2229:2261 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 5 6 dep mechanism 1079:1087 arg1 behind 1089:1094 behind 1089:1094 behind safranal-induced apoptosis 1089:1121 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 10 7 theme daily 1666:1670 arg1 diets 1672:1676 daily diets 1666:1676 daily diets 1666:1676 These results highlight the impact of safranal as a potent anticancer compound on TNBCs which also can be strongly used in daily diets. 35240313 11 8 theme cell 1754:1757 arg1 lines 1759:1763 MDA-MB-231 cell lines 1743:1763 MDA-MB-231 cell lines 1743:1763 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 7 9 theme DNA 1261:1263 arg1 fragmentation 1265:1277 DNA fragmentation 1261:1277 DNA fragmentation 1261:1277 It regulates proteins considered as activator of DNA fragmentation and apoptosis mediators. 35240313 14 10 theme analysis 2390:2397 arg1 results 2364:2370 The results 2360:2370 The results of bioinformatics analysis 2360:2397 The results of bioinformatics analysis revealed the multifunction role of safranal on MDA-MB-231 cell lines. 35240313 10 11 used used 1658:1661 arg2 TNBCs 1625:1629 TNBCs 1625:1629 TNBCs which also can be strongly used in daily diets 1625:1676 These results highlight the impact of safranal as a potent anticancer compound on TNBCs which also can be strongly used in daily diets. 35240313 8 12 theme glycoproteins 1348:1360 arg1 sialylation 1333:1343 sialylation 1333:1343 sialylation of glycoproteins involving in cellular adhesion, migration and survival 1333:1415 Moreover, safranal regulates sialylation of glycoproteins involving in cellular adhesion, migration and survival. 35240313 14 13 theme MDA-MB-231 2446:2455 arg1 lines 2462:2466 MDA-MB-231 cell lines 2446:2466 MDA-MB-231 cell lines 2446:2466 The results of bioinformatics analysis revealed the multifunction role of safranal on MDA-MB-231 cell lines. 35240313 13 14 theme proteomics 2170:2179 arg1 combination 2123:2133 a combination 2121:2133 a combination of TMT-based labeling quantitative proteomics 2121:2179 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 14 theme proteomics 2170:2179 arg1 dioxide 2194:2200 titanium dioxide 2185:2200 titanium dioxide 2185:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 1 15 theme aggressive 186:195 arg1 cancer 166:171 Triple-negative breast cancer 143:171 Triple-negative breast cancer (TNBC) 143:178 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 1 15 theme aggressive 186:195 arg1 subtype 197:203 an aggressive subtype 183:203 an aggressive subtype of breast cancer with no efficient treatment 183:248 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 0 16 theme cell 131:134 arg1 lines 136:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 13 17 from time-points 2085:2095 arg1 set 2034:2036 three set 2028:2036 three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2028:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 17 from time-points 2085:2095 arg1 lines 2054:2058 treated cell lines 2041:2058 treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2041:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 17 from time-points 2085:2095 arg1 three 2100:2104 three 2100:2104 three 2100:2104 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 2 18 theme approaches 309:318 arg1 importance 282:291 the importance 278:291 the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes 278:424 Researchers have indicated the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes. 35240313 15 19 theme DNA 2598:2600 arg1 fragmentation 2602:2614 DNA fragmentation 2598:2614 DNA fragmentation 2598:2614 Safranal mainly dysregulates mitochondrial function, inhibits metabolism and starts initial signaling of apoptosis which lead to DNA fragmentation. 35240313 1 20 theme cancer 215:220 arg1 cancer 166:171 Triple-negative breast cancer 143:171 Triple-negative breast cancer (TNBC) 143:178 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 1 20 theme cancer 215:220 arg1 subtype 197:203 an aggressive subtype 183:203 an aggressive subtype of breast cancer with no efficient treatment 183:248 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 5 21 theme safranal-induced 1096:1111 arg1 apoptosis 1113:1121 safranal-induced apoptosis 1096:1121 safranal-induced apoptosis 1096:1121 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 18 22 theme drugs 3067:3071 arg1 designing 3033:3041 designing 3033:3041 designing 3033:3041 The results provide a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies. 35240313 2 23 from importance 282:291 arg1 proteome 323:330 proteome 323:330 proteome 323:330 Researchers have indicated the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes. 35240313 2 23 from importance 282:291 arg1 treatment 407:415 treatment 407:415 treatment 407:415 Researchers have indicated the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes. 35240313 2 23 from importance 282:291 arg1 diagnosis 393:401 diagnosis 393:401 diagnosis 393:401 Researchers have indicated the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes. 35240313 17 24 theme sialylation 2807:2817 arg1 level 2819:2823 the sialylation level 2803:2823 the sialylation level 2803:2823 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 13 25 link N-linked 2240:2247 arg1 glycopeptides 2249:2261 sialylated N-linked glycopeptides 2229:2261 sialylated N-linked glycopeptides 2229:2261 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 26 from MDA-MB-231 2000:2009 arg1 understanding 1954:1966 an understanding 1951:1966 an understanding of safranal cytotoxic effect on MDA-MB-231 1951:2009 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 27 theme titanium 2185:2192 arg1 dioxide 2194:2200 titanium dioxide 2185:2200 titanium dioxide 2185:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 3 28 theme therapeutic 560:570 arg1 strategies 572:581 therapeutic strategies 560:581 therapeutic strategies 560:581 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 15 29 theme apoptosis 2574:2582 arg1 signaling 2561:2569 initial signaling 2553:2569 initial signaling of apoptosis which lead to DNA fragmentation 2553:2614 Safranal mainly dysregulates mitochondrial function, inhibits metabolism and starts initial signaling of apoptosis which lead to DNA fragmentation. 35240313 1 30 theme Triple-negative 143:157 arg1 cancer 166:171 Triple-negative breast cancer 143:171 Triple-negative breast cancer (TNBC) 143:178 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 1 30 theme Triple-negative 143:157 arg1 subtype 197:203 an aggressive subtype 183:203 an aggressive subtype of breast cancer with no efficient treatment 183:248 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 1 30 theme Triple-negative 143:157 arg1 TNBC 174:177 TNBC 174:177 TNBC 174:177 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 16 31 theme down-regulation 2659:2673 arg1 majority 2647:2654 the majority 2643:2654 the majority of down-regulation 2643:2673 Moreover, safranal caused the majority of down-regulation in sialylation profile in all time-points. 35240313 14 32 theme multifunction 2412:2424 arg1 role 2426:2429 the multifunction role 2408:2429 the multifunction role of safranal on MDA-MB-231 cell lines 2408:2466 The results of bioinformatics analysis revealed the multifunction role of safranal on MDA-MB-231 cell lines. 35240313 18 33 theme triple 2988:2993 arg1 cancer 3011:3016 triple negative breast cancer 2988:3016 triple negative breast cancer 2988:3016 The results provide a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies. 35240313 5 34 theme cells 925:929 arg1 proteomics 859:868 a comprehensive proteomics and sialiomics analysis 843:892 proteomics 859:868 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 5 34 theme cells 925:929 arg1 analysis 885:892 a comprehensive proteomics and sialiomics analysis 843:892 analysis 885:892 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 10 35 from compound 1613:1620 arg1 TNBCs 1625:1629 TNBCs 1625:1629 TNBCs which also can be strongly used in daily diets 1625:1676 These results highlight the impact of safranal as a potent anticancer compound on TNBCs which also can be strongly used in daily diets. 35240313 13 36 theme cytotoxic 1980:1988 arg1 effect 1990:1995 safranal cytotoxic effect 1971:1995 safranal cytotoxic effect on MDA-MB-231 1971:2009 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 37 theme labeling 2148:2155 arg1 proteomics 2170:2179 TMT-based labeling quantitative proteomics 2138:2179 TMT-based labeling quantitative proteomics 2138:2179 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 18 38 theme anticancer 3056:3065 arg1 drugs 3067:3071 effective anticancer drugs 3046:3071 effective anticancer drugs 3046:3071 The results provide a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies. 35240313 13 39 theme effect 2352:2357 arg1 mechanisms 2329:2338 the more detailed mechanisms 2311:2338 the more detailed mechanisms of safranal effect 2311:2357 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 17 40 from dysregulation 2786:2798 arg1 proteins 2838:2845 important proteins 2828:2845 important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs) 2828:2932 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 17 40 from dysregulation 2786:2798 arg1 molecules 2917:2925 cell adhesion molecules 2903:2925 cell adhesion molecules (CAMs) 2903:2932 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 17 40 from dysregulation 2786:2798 arg1 receptor 2890:2897 tumor necrosis factor receptor 2868:2897 tumor necrosis factor receptor 2868:2897 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 17 40 from dysregulation 2786:2798 arg1 integrins 2857:2865 integrins 2857:2865 integrins 2857:2865 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 14 41 theme bioinformatics 2375:2388 arg1 analysis 2390:2397 bioinformatics analysis 2375:2397 bioinformatics analysis 2375:2397 The results of bioinformatics analysis revealed the multifunction role of safranal on MDA-MB-231 cell lines. 35240313 0 42 theme negative 97:104 arg1 lines 136:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 9 43 from alteration 1473:1482 arg1 receptors 1532:1540 important signaling receptors 1512:1540 important signaling receptors 1512:1540 It suppresses cell survival and metastasis through the alteration of the sialylation level on important signaling receptors. 35240313 5 44 theme TMT 957:959 arg1 labeling 961:968 TMT labeling 957:968 TMT labeling 957:968 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 0 45 theme breast 117:122 arg1 lines 136:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 15 46 theme mitochondrial 2498:2510 arg1 function 2512:2519 mitochondrial function 2498:2519 mitochondrial function 2498:2519 Safranal mainly dysregulates mitochondrial function, inhibits metabolism and starts initial signaling of apoptosis which lead to DNA fragmentation. 35240313 5 47 theme N-linked 1016:1023 arg1 glycopeptides 1025:1037 sialylated N-linked glycopeptides 1005:1037 sialylated N-linked glycopeptides 1005:1037 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 17 48 theme factor 2883:2888 arg1 receptor 2890:2897 tumor necrosis factor receptor 2868:2897 tumor necrosis factor receptor 2868:2897 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 16 49 theme sialylation 2678:2688 arg1 profile 2690:2696 sialylation profile 2678:2696 sialylation profile 2678:2696 Moreover, safranal caused the majority of down-regulation in sialylation profile in all time-points. 35240313 10 50 theme safranal 1581:1588 arg1 compound 1613:1620 a potent anticancer compound 1593:1620 a potent anticancer compound on TNBCs which also can be strongly used in daily diets 1593:1676 These results highlight the impact of safranal as a potent anticancer compound on TNBCs which also can be strongly used in daily diets. 35240313 10 50 theme safranal 1581:1588 arg1 impact 1571:1576 the impact 1567:1576 the impact of safranal 1567:1588 These results highlight the impact of safranal as a potent anticancer compound on TNBCs which also can be strongly used in daily diets. 35240313 0 51 theme Comprehensive 0:12 arg1 proteomics 14:23 Comprehensive proteomics 0:23 Comprehensive proteomics 0:23 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 4 52 theme cytotoxic 768:776 arg1 effect 778:783 a significant cytotoxic effect 754:783 a significant cytotoxic effect on MDA-MB-231 in comparison to normal cells 754:827 Based on our study, safranal, which is a non-toxic compound in orally intakes, exhibits a significant cytotoxic effect on MDA-MB-231 in comparison to normal cells. 35240313 3 53 theme modifications 495:507 arg1 tool 532:535 a tool 530:535 a tool in cancer diagnosis or therapeutic strategies 530:581 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 3 53 theme modifications 495:507 arg1 one 482:484 one 482:484 one 482:484 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 3 53 theme modifications 495:507 arg1 modifications 495:507 these modifications 489:507 these modifications 489:507 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 17 54 dep survival 2750:2757 arg1 the 2741:2743 the 2741:2743 the 2741:2743 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 5 55 theme dioxide 983:989 arg1 enrichment 991:1000 TMT labeling and titanium dioxide enrichment 957:1000 TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides 957:1037 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 1 56 theme breast 159:164 arg1 cancer 166:171 Triple-negative breast cancer 143:171 Triple-negative breast cancer (TNBC) 143:178 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 1 56 theme breast 159:164 arg1 subtype 197:203 an aggressive subtype 183:203 an aggressive subtype of breast cancer with no efficient treatment 183:248 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 1 56 theme breast 159:164 arg1 TNBC 174:177 TNBC 174:177 TNBC 174:177 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 17 57 theme adhesion 2908:2915 arg1 molecules 2917:2925 cell adhesion molecules 2903:2925 cell adhesion molecules (CAMs) 2903:2932 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 17 57 theme adhesion 2908:2915 arg1 CAMs 2928:2931 CAMs 2928:2931 CAMs 2928:2931 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 10 58 theme anticancer 1602:1611 arg1 compound 1613:1620 a potent anticancer compound 1593:1620 a potent anticancer compound on TNBCs which also can be strongly used in daily diets 1593:1676 These results highlight the impact of safranal as a potent anticancer compound on TNBCs which also can be strongly used in daily diets. 35240313 10 58 theme anticancer 1602:1611 arg1 impact 1571:1576 the impact 1567:1576 the impact of safranal 1567:1588 These results highlight the impact of safranal as a potent anticancer compound on TNBCs which also can be strongly used in daily diets. 35240313 12 59 dep demonstrated 1888:1899 arg1 compound 1879:1886 the only compound 1870:1886 the only compound 1870:1886 Safranal was the only compound demonstrated the anti-proliferation effect. 35240313 17 60 theme important 2828:2836 arg1 proteins 2838:2845 important proteins 2828:2845 important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs) 2828:2932 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 17 60 theme important 2828:2836 arg1 molecules 2917:2925 cell adhesion molecules 2903:2925 cell adhesion molecules (CAMs) 2903:2932 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 17 60 theme important 2828:2836 arg1 receptor 2890:2897 tumor necrosis factor receptor 2868:2897 tumor necrosis factor receptor 2868:2897 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 17 60 theme important 2828:2836 arg1 integrins 2857:2865 integrins 2857:2865 integrins 2857:2865 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 5 61 theme molecular 1069:1077 arg1 mechanism 1079:1087 the underlying molecular mechanism 1054:1087 the underlying molecular mechanism behind safranal-induced apoptosis 1054:1121 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 3 62 theme acid-containing 434:448 arg1 glycopeptides 450:462 Sialic acid-containing glycopeptides 427:462 Sialic acid-containing glycopeptides (the sialiome) 427:477 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 3 62 theme acid-containing 434:448 arg1 sialiome 469:476 the sialiome 465:476 the sialiome 465:476 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 9 63 dep cell 1432:1435 arg1 survival 1437:1444 survival 1437:1444 survival 1437:1444 It suppresses cell survival and metastasis through the alteration of the sialylation level on important signaling receptors. 35240313 11 64 theme saffron 1786:1792 arg1 components 1794:1803 the purified saffron components 1773:1803 the purified saffron components (total crocin, picrocrocin, crocin I and safranal) 1773:1854 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 64 theme saffron 1786:1792 arg1 crocin 1812:1817 total crocin 1806:1817 total crocin 1806:1817 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 64 theme saffron 1786:1792 arg1 I 1840:1840 crocin I 1833:1840 crocin I 1833:1840 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 64 theme saffron 1786:1792 arg1 safranal 1846:1853 safranal 1846:1853 safranal 1846:1853 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 64 theme saffron 1786:1792 arg1 picrocrocin 1820:1830 picrocrocin 1820:1830 picrocrocin 1820:1830 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 0 65 theme anti-proliferative 47:64 arg1 activity 66:73 the anti-proliferative activity 43:73 the anti-proliferative activity of safranal 43:85 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 0 66 from sialiomics 29:38 arg1 lines 136:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 6 67 theme dysfunction 1199:1209 arg1 inhibition 1156:1165 the inhibition 1152:1165 the inhibition of metabolism and mitochondrial dysfunction 1152:1209 Safranal has main effect on the inhibition of metabolism and mitochondrial dysfunction. 35240313 13 68 gly glycopeptides 2249:2261 arg2 glycopeptides 2249:2261 sialylated N-linked glycopeptides 2229:2261 sialylated N-linked glycopeptides 2229:2261 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 2 69 theme post-translation 346:361 arg1 modifications 363:375 different post-translation modifications 336:375 different post-translation modifications 336:375 Researchers have indicated the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes. 35240313 9 70 theme sialylation 1491:1501 arg1 level 1503:1507 the sialylation level 1487:1507 the sialylation level 1487:1507 It suppresses cell survival and metastasis through the alteration of the sialylation level on important signaling receptors. 35240313 13 71 theme 24 h 2080:2083 arg1 time-points 2085:2095 24 h time-points 2080:2095 24 h time-points 2080:2095 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 72 dep order 1935:1939 arg1 obtain 1944:1949 obtain 1944:1949 to obtain an understanding of safranal cytotoxic effect on MDA-MB-231 1941:2009 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 73 dep -based 2208:2213 arg1 set 2034:2036 three set 2028:2036 three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2028:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 73 dep -based 2208:2213 arg1 lines 2054:2058 treated cell lines 2041:2058 treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2041:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 1 74 theme efficient 230:238 arg1 treatment 240:248 no efficient treatment 227:248 no efficient treatment 227:248 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 11 75 theme crocin 1833:1838 arg1 I 1840:1840 crocin I 1833:1840 crocin I 1833:1840 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 75 theme crocin 1833:1838 arg1 components 1794:1803 the purified saffron components 1773:1803 the purified saffron components (total crocin, picrocrocin, crocin I and safranal) 1773:1854 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 76 theme MDA-MB-231 1743:1752 arg1 lines 1759:1763 MDA-MB-231 cell lines 1743:1763 MDA-MB-231 cell lines 1743:1763 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 9 77 theme signaling 1522:1530 arg1 receptors 1532:1540 important signaling receptors 1512:1540 important signaling receptors 1512:1540 It suppresses cell survival and metastasis through the alteration of the sialylation level on important signaling receptors. 35240313 15 78 theme initial 2553:2559 arg1 signaling 2561:2569 initial signaling 2553:2569 initial signaling of apoptosis which lead to DNA fragmentation 2553:2614 Safranal mainly dysregulates mitochondrial function, inhibits metabolism and starts initial signaling of apoptosis which lead to DNA fragmentation. 35240313 17 79 theme tumor 2868:2872 arg1 factor 2883:2888 tumor necrosis factor 2868:2888 tumor necrosis factor receptor 2868:2897 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 3 80 from tool 532:535 arg1 diagnosis 547:555 cancer diagnosis 540:555 cancer diagnosis 540:555 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 3 80 from tool 532:535 arg1 strategies 572:581 therapeutic strategies 560:581 therapeutic strategies 560:581 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 2 81 theme quantitative 296:307 arg1 approaches 309:318 quantitative approaches 296:318 quantitative approaches 296:318 Researchers have indicated the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes. 35240313 13 82 theme sialylated 2229:2238 arg1 glycopeptides 2249:2261 sialylated N-linked glycopeptides 2229:2261 sialylated N-linked glycopeptides 2229:2261 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 5 83 link N-linked 1016:1023 arg1 glycopeptides 1025:1037 sialylated N-linked glycopeptides 1005:1037 sialylated N-linked glycopeptides 1005:1037 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 13 84 from 30 min 2063:2068 arg1 set 2034:2036 three set 2028:2036 three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2028:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 84 from 30 min 2063:2068 arg1 lines 2054:2058 treated cell lines 2041:2058 treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2041:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 84 from 30 min 2063:2068 arg1 three 2100:2104 three 2100:2104 three 2100:2104 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 85 from 12 h 2071:2074 arg1 set 2034:2036 three set 2028:2036 three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2028:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 85 from 12 h 2071:2074 arg1 lines 2054:2058 treated cell lines 2041:2058 treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2041:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 85 from 12 h 2071:2074 arg1 three 2100:2104 three 2100:2104 three 2100:2104 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 11 86 theme lines 1759:1763 arg1 viability 1730:1738 the cell viability 1721:1738 the cell viability of MDA-MB-231 cell lines 1721:1763 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 14 87 theme cell 2457:2460 arg1 lines 2462:2466 MDA-MB-231 cell lines 2446:2466 MDA-MB-231 cell lines 2446:2466 The results of bioinformatics analysis revealed the multifunction role of safranal on MDA-MB-231 cell lines. 35240313 5 88 theme safranal 897:904 arg1 cells 925:929 safranal treated MDA-MB-231 cells 897:929 safranal treated MDA-MB-231 cells 897:929 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 18 89 theme targets 2976:2982 arg1 set 2957:2959 a set 2955:2959 a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies 2955:3103 The results provide a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies. 35240313 18 89 theme targets 2976:2982 arg1 targets 2976:2982 therapeutic targets 2964:2982 therapeutic targets for triple negative breast cancer 2964:3016 The results provide a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies. 35240313 17 90 theme necrosis 2874:2881 arg1 factor 2883:2888 tumor necrosis factor 2868:2888 tumor necrosis factor receptor 2868:2897 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 5 91 theme comprehensive 845:857 arg1 proteomics 859:868 a comprehensive proteomics and sialiomics analysis 843:892 proteomics 859:868 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 13 92 from lines 2054:2058 arg1 12 h 2071:2074 12 h 2071:2074 12 h 2071:2074 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 92 from lines 2054:2058 arg1 time-points 2085:2095 24 h time-points 2080:2095 24 h time-points 2080:2095 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 92 from lines 2054:2058 arg1 30 min 2063:2068 30 min 2063:2068 30 min 2063:2068 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 8 93 gly sialylation 1333:1343 arg1 glycoproteins 1348:1360 glycoproteins 1348:1360 glycoproteins involving in cellular adhesion, migration and survival 1348:1415 Moreover, safranal regulates sialylation of glycoproteins involving in cellular adhesion, migration and survival. 35240313 3 94 dep cancer 633:638 arg1 migration 640:648 migration 640:648 migration 640:648 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 1 95 theme breast 208:213 arg1 cancer 215:220 breast cancer 208:220 breast cancer 208:220 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 8 96 theme cellular 1375:1382 arg1 adhesion 1384:1391 cellular adhesion 1375:1391 cellular adhesion 1375:1391 Moreover, safranal regulates sialylation of glycoproteins involving in cellular adhesion, migration and survival. 35240313 7 97 theme apoptosis 1283:1291 arg1 mediators 1293:1301 apoptosis mediators 1283:1301 apoptosis mediators 1283:1301 It regulates proteins considered as activator of DNA fragmentation and apoptosis mediators. 35240313 8 98 gly glycoproteins 1348:1360 arg1 glycoproteins 1348:1360 glycoproteins 1348:1360 glycoproteins involving in cellular adhesion, migration and survival 1348:1415 Moreover, safranal regulates sialylation of glycoproteins involving in cellular adhesion, migration and survival. 35240313 13 99 from set 2034:2036 arg1 12 h 2071:2074 12 h 2071:2074 12 h 2071:2074 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 99 from set 2034:2036 arg1 time-points 2085:2095 24 h time-points 2080:2095 24 h time-points 2080:2095 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 99 from set 2034:2036 arg1 30 min 2063:2068 30 min 2063:2068 30 min 2063:2068 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 18 100 theme therapeutic 2964:2974 arg1 targets 2976:2982 therapeutic targets 2964:2982 therapeutic targets for triple negative breast cancer 2964:3016 The results provide a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies. 35240313 14 101 theme safranal 2434:2441 arg1 role 2426:2429 the multifunction role 2408:2429 the multifunction role of safranal on MDA-MB-231 cell lines 2408:2466 The results of bioinformatics analysis revealed the multifunction role of safranal on MDA-MB-231 cell lines. 35240313 13 102 from understanding 1954:1966 arg1 MDA-MB-231 2000:2009 MDA-MB-231 2000:2009 MDA-MB-231 2000:2009 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 5 103 theme treated 906:912 arg1 cells 925:929 safranal treated MDA-MB-231 cells 897:929 safranal treated MDA-MB-231 cells 897:929 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 17 104 theme level 2819:2823 arg1 dysregulation 2786:2798 dysregulation 2786:2798 dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs) 2786:2932 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 13 105 from effect 1990:1995 arg1 MDA-MB-231 2000:2009 MDA-MB-231 2000:2009 MDA-MB-231 2000:2009 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 17 106 theme cell 2745:2748 arg1 survival 2750:2757 cell survival 2745:2757 cell survival 2745:2757 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 2 107 dep proteome 323:330 arg1 studies 377:383 studies 377:383 studies 377:383 Researchers have indicated the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes. 35240313 2 107 dep proteome 323:330 arg1 both 385:388 both 385:388 both 385:388 Researchers have indicated the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes. 35240313 0 108 theme safranal 78:85 arg1 activity 66:73 the anti-proliferative activity 43:73 the anti-proliferative activity of safranal 43:85 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 18 109 theme effective 3046:3054 arg1 drugs 3067:3071 effective anticancer drugs 3046:3071 effective anticancer drugs 3046:3071 The results provide a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies. 35240313 5 110 theme MDA-MB-231 914:923 arg1 cells 925:929 safranal treated MDA-MB-231 cells 897:929 safranal treated MDA-MB-231 cells 897:929 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 6 111 contain has 1133:1135 arg2 effect 1142:1147 main effect 1137:1147 main effect 1137:1147 Safranal has main effect on the inhibition of metabolism and mitochondrial dysfunction. 35240313 6 111 contain has 1133:1135 arg1 Safranal 1124:1131 Safranal 1124:1131 Safranal 1124:1131 Safranal has main effect on the inhibition of metabolism and mitochondrial dysfunction. 35240313 13 112 theme glycopeptides 2249:2261 arg1 strategy 2292:2299 a strategy 2290:2299 a strategy to follow the more detailed mechanisms of safranal effect 2290:2357 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 112 theme glycopeptides 2249:2261 arg1 enrichment 2215:2224 the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment 2024:2224 the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides 2024:2261 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 113 theme safranal 1971:1978 arg1 effect 1990:1995 safranal cytotoxic effect 1971:1995 safranal cytotoxic effect on MDA-MB-231 1971:2009 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 7 114 theme mediators 1293:1301 arg1 activator 1248:1256 activator 1248:1256 activator of DNA fragmentation and apoptosis mediators 1248:1301 It regulates proteins considered as activator of DNA fragmentation and apoptosis mediators. 35240313 0 115 theme triple 90:95 arg1 lines 136:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 13 116 theme TMT-based 2138:2146 arg1 proteomics 2170:2179 TMT-based labeling quantitative proteomics 2138:2179 TMT-based labeling quantitative proteomics 2138:2179 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 117 theme safranal 2343:2350 arg1 effect 2352:2357 safranal effect 2343:2357 safranal effect 2343:2357 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 5 118 gly sialylated 1005:1014 arg1 glycopeptides 1025:1037 sialylated N-linked glycopeptides 1005:1037 sialylated N-linked glycopeptides 1005:1037 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 0 119 from proteomics 14:23 arg1 lines 136:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 4 120 theme non-toxic 707:715 arg1 safranal 686:693 safranal 686:693 safranal 686:693 Based on our study, safranal, which is a non-toxic compound in orally intakes, exhibits a significant cytotoxic effect on MDA-MB-231 in comparison to normal cells. 35240313 4 120 theme non-toxic 707:715 arg1 compound 717:724 a non-toxic compound 705:724 a non-toxic compound in orally intakes 705:742 Based on our study, safranal, which is a non-toxic compound in orally intakes, exhibits a significant cytotoxic effect on MDA-MB-231 in comparison to normal cells. 35240313 13 121 theme effect 1990:1995 arg1 understanding 1954:1966 an understanding 1951:1966 an understanding of safranal cytotoxic effect on MDA-MB-231 1951:2009 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 13 122 theme sialiomics 2267:2276 arg1 analysis 2278:2285 sialiomics analysis 2267:2285 sialiomics analysis 2267:2285 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 0 123 theme MDA-MB-231 106:115 arg1 lines 136:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 13 124 theme quantitative 2157:2168 arg1 proteomics 2170:2179 TMT-based labeling quantitative proteomics 2138:2179 TMT-based labeling quantitative proteomics 2138:2179 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 3 125 gly glycopeptides 450:462 arg2 sialiome 469:476 the sialiome 465:476 the sialiome 465:476 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 3 125 gly glycopeptides 450:462 arg2 glycopeptides 450:462 Sialic acid-containing glycopeptides 427:462 Sialic acid-containing glycopeptides (the sialiome) 427:477 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 5 126 theme enrichment 991:1000 arg1 combination 942:952 a combination 940:952 a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides 940:1037 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 0 127 theme cancer 124:129 arg1 lines 136:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 triple negative MDA-MB-231 breast cancer cell lines 90:140 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 4 128 from effect 778:783 arg1 comparison 802:811 comparison 802:811 comparison to normal cells 802:827 Based on our study, safranal, which is a non-toxic compound in orally intakes, exhibits a significant cytotoxic effect on MDA-MB-231 in comparison to normal cells. 35240313 4 128 from effect 778:783 arg1 MDA-MB-231 788:797 MDA-MB-231 788:797 MDA-MB-231 788:797 Based on our study, safranal, which is a non-toxic compound in orally intakes, exhibits a significant cytotoxic effect on MDA-MB-231 in comparison to normal cells. 35240313 5 129 theme sialylated 1005:1014 arg1 glycopeptides 1025:1037 sialylated N-linked glycopeptides 1005:1037 sialylated N-linked glycopeptides 1005:1037 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 13 130 dep three 2100:2104 arg1 replicates 2106:2115 replicates 2106:2115 replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2106:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 2 131 dep diagnosis 393:401 arg1 purposes 417:424 purposes 417:424 purposes 417:424 Researchers have indicated the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes. 35240313 7 132 theme fragmentation 1265:1277 arg1 activator 1248:1256 activator 1248:1256 activator of DNA fragmentation and apoptosis mediators 1248:1301 It regulates proteins considered as activator of DNA fragmentation and apoptosis mediators. 35240313 18 133 theme negative 2995:3002 arg1 cancer 3011:3016 triple negative breast cancer 2988:3016 triple negative breast cancer 2988:3016 The results provide a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies. 35240313 13 134 theme cell 2049:2052 arg1 lines 2054:2058 treated cell lines 2041:2058 treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide 2041:2200 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 5 135 theme labeling 961:968 arg1 enrichment 991:1000 TMT labeling and titanium dioxide enrichment 957:1000 TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides 957:1037 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 6 136 theme main 1137:1140 arg1 effect 1142:1147 main effect 1137:1147 main effect 1137:1147 Safranal has main effect on the inhibition of metabolism and mitochondrial dysfunction. 35240313 3 137 theme Sialic 427:432 arg1 glycopeptides 450:462 Sialic acid-containing glycopeptides 427:462 Sialic acid-containing glycopeptides (the sialiome) 427:477 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 3 137 theme Sialic 427:432 arg1 sialiome 469:476 the sialiome 465:476 the sialiome 465:476 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 5 138 theme titanium 974:981 arg1 dioxide 983:989 titanium dioxide 974:989 titanium dioxide 974:989 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 18 139 theme targeted 3086:3093 arg1 therapies 3095:3103 targeted therapies 3086:3103 targeted therapies 3086:3103 The results provide a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies. 35240313 17 140 theme cell 2903:2906 arg1 molecules 2917:2925 cell adhesion molecules 2903:2925 cell adhesion molecules (CAMs) 2903:2932 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 17 140 theme cell 2903:2906 arg1 CAMs 2928:2931 CAMs 2928:2931 CAMs 2928:2931 Safranal also declines the cell survival, adhesion and migration by dysregulation of the sialylation level in important proteins including integrins, tumor necrosis factor receptor and cell adhesion molecules (CAMs). 35240313 4 141 theme significant 756:766 arg1 effect 778:783 a significant cytotoxic effect 754:783 a significant cytotoxic effect on MDA-MB-231 in comparison to normal cells 754:827 Based on our study, safranal, which is a non-toxic compound in orally intakes, exhibits a significant cytotoxic effect on MDA-MB-231 in comparison to normal cells. 35240313 13 142 theme detailed 2320:2327 arg1 mechanisms 2329:2338 the more detailed mechanisms 2311:2338 the more detailed mechanisms of safranal effect 2311:2357 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 1 143 with subtype 197:203 arg1 treatment 240:248 no efficient treatment 227:248 no efficient treatment 227:248 Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no efficient treatment. 35240313 5 144 theme underlying 1058:1067 arg1 mechanism 1079:1087 the underlying molecular mechanism 1054:1087 the underlying molecular mechanism behind safranal-induced apoptosis 1054:1121 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 5 145 gly glycopeptides 1025:1037 arg2 glycopeptides 1025:1037 sialylated N-linked glycopeptides 1005:1037 sialylated N-linked glycopeptides 1005:1037 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 10 146 theme potent 1595:1600 arg1 compound 1613:1620 a potent anticancer compound 1593:1620 a potent anticancer compound on TNBCs which also can be strongly used in daily diets 1593:1676 These results highlight the impact of safranal as a potent anticancer compound on TNBCs which also can be strongly used in daily diets. 35240313 10 146 theme potent 1595:1600 arg1 impact 1571:1576 the impact 1567:1576 the impact of safranal 1567:1588 These results highlight the impact of safranal as a potent anticancer compound on TNBCs which also can be strongly used in daily diets. 35240313 11 147 theme purified 1777:1784 arg1 components 1794:1803 the purified saffron components 1773:1803 the purified saffron components (total crocin, picrocrocin, crocin I and safranal) 1773:1854 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 147 theme purified 1777:1784 arg1 crocin 1812:1817 total crocin 1806:1817 total crocin 1806:1817 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 147 theme purified 1777:1784 arg1 I 1840:1840 crocin I 1833:1840 crocin I 1833:1840 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 147 theme purified 1777:1784 arg1 safranal 1846:1853 safranal 1846:1853 safranal 1846:1853 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 147 theme purified 1777:1784 arg1 picrocrocin 1820:1830 picrocrocin 1820:1830 picrocrocin 1820:1830 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 148 dep components 1794:1803 arg1 I 1840:1840 crocin I 1833:1840 crocin I 1833:1840 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 148 dep components 1794:1803 arg1 crocin 1812:1817 total crocin 1806:1817 total crocin 1806:1817 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 148 dep components 1794:1803 arg1 components 1794:1803 the purified saffron components 1773:1803 the purified saffron components (total crocin, picrocrocin, crocin I and safranal) 1773:1854 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 148 dep components 1794:1803 arg1 safranal 1846:1853 safranal 1846:1853 safranal 1846:1853 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 148 dep components 1794:1803 arg1 picrocrocin 1820:1830 picrocrocin 1820:1830 picrocrocin 1820:1830 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 149 theme first 1696:1700 arg1 step 1702:1705 first step 1696:1705 first step 1696:1705 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 0 150 theme activity 66:73 arg1 sialiomics 29:38 sialiomics 29:38 sialiomics 29:38 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 0 150 theme activity 66:73 arg1 proteomics 14:23 Comprehensive proteomics 0:23 Comprehensive proteomics 0:23 Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines. 35240313 18 151 theme breast 3004:3009 arg1 cancer 3011:3016 triple negative breast cancer 2988:3016 triple negative breast cancer 2988:3016 The results provide a set of therapeutic targets for triple negative breast cancer which can help designing of effective anticancer drugs specially in targeted therapies. 35240313 14 152 from role 2426:2429 arg1 lines 2462:2466 MDA-MB-231 cell lines 2446:2466 MDA-MB-231 cell lines 2446:2466 The results of bioinformatics analysis revealed the multifunction role of safranal on MDA-MB-231 cell lines. 35240313 3 153 used used 522:525 arg2 tool 532:535 a tool 530:535 a tool in cancer diagnosis or therapeutic strategies 530:581 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 3 153 used used 522:525 arg2 modifications 495:507 these modifications 489:507 these modifications 489:507 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 3 153 used used 522:525 arg2 one 482:484 one 482:484 one 482:484 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 13 154 gly sialylated 2229:2238 arg1 glycopeptides 2249:2261 sialylated N-linked glycopeptides 2229:2261 sialylated N-linked glycopeptides 2229:2261 In order to obtain an understanding of safranal cytotoxic effect on MDA-MB-231, we designed the three set of treated cell lines in 30 min, 12 h and 24 h time-points in three replicates and a combination of TMT-based labeling quantitative proteomics and titanium dioxide (TiO2)-based enrichment of sialylated N-linked glycopeptides for sialiomics analysis as a strategy to follow the more detailed mechanisms of safranal effect. 35240313 5 155 theme glycopeptides 1025:1037 arg1 enrichment 991:1000 TMT labeling and titanium dioxide enrichment 957:1000 TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides 957:1037 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 12 156 theme anti-proliferation 1905:1922 arg1 effect 1924:1929 the anti-proliferation effect 1901:1929 the anti-proliferation effect 1901:1929 Safranal was the only compound demonstrated the anti-proliferation effect. 35240313 6 157 theme mitochondrial 1185:1197 arg1 dysfunction 1199:1209 mitochondrial dysfunction 1185:1209 mitochondrial dysfunction 1185:1209 Safranal has main effect on the inhibition of metabolism and mitochondrial dysfunction. 35240313 11 158 theme total 1806:1810 arg1 components 1794:1803 the purified saffron components 1773:1803 the purified saffron components (total crocin, picrocrocin, crocin I and safranal) 1773:1854 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 11 158 theme total 1806:1810 arg1 crocin 1812:1817 total crocin 1806:1817 total crocin 1806:1817 SIGNIFICANCE: In first step, we evaluated the cell viability of MDA-MB-231 cell lines against the purified saffron components (total crocin, picrocrocin, crocin I and safranal). 35240313 2 159 theme different 336:344 arg1 modifications 363:375 different post-translation modifications 336:375 different post-translation modifications 336:375 Researchers have indicated the importance of quantitative approaches on proteome and different post-translation modifications studies both in diagnosis and treatment purposes. 35240313 9 160 theme level 1503:1507 arg1 alteration 1473:1482 the alteration 1469:1482 the alteration of the sialylation level on important signaling receptors 1469:1540 It suppresses cell survival and metastasis through the alteration of the sialylation level on important signaling receptors. 35240313 5 161 theme sialiomics 874:883 arg1 analysis 885:892 a comprehensive proteomics and sialiomics analysis 843:892 analysis 885:892 We conducted a comprehensive proteomics and sialiomics analysis of safranal treated MDA-MB-231 cells by using a combination of TMT labeling and titanium dioxide enrichment of sialylated N-linked glycopeptides to investigate the underlying molecular mechanism behind safranal-induced apoptosis. 35240313 6 162 theme metabolism 1170:1179 arg1 inhibition 1156:1165 the inhibition 1152:1165 the inhibition of metabolism and mitochondrial dysfunction 1152:1209 Safranal has main effect on the inhibition of metabolism and mitochondrial dysfunction. 35240313 4 163 theme normal 816:821 arg1 cells 823:827 normal cells 816:827 normal cells 816:827 Based on our study, safranal, which is a non-toxic compound in orally intakes, exhibits a significant cytotoxic effect on MDA-MB-231 in comparison to normal cells. 35240313 3 164 theme cancer 540:545 arg1 diagnosis 547:555 cancer diagnosis 540:555 cancer diagnosis 540:555 Sialic acid-containing glycopeptides (the sialiome) is one of these modifications which can be used as a tool in cancer diagnosis or therapeutic strategies since the sialylation is strongly associated with cancer migration and metastasis. 35240313 4 165 from compound 717:724 arg1 intakes 736:742 intakes 736:742 orally intakes 729:742 Based on our study, safranal, which is a non-toxic compound in orally intakes, exhibits a significant cytotoxic effect on MDA-MB-231 in comparison to normal cells. 35240313 9 166 theme important 1512:1520 arg1 receptors 1532:1540 important signaling receptors 1512:1540 important signaling receptors 1512:1540 It suppresses cell survival and metastasis through the alteration of the sialylation level on important signaling receptors. 36984829 6 0 theme orthogonal 901:910 arg1 squares 926:932 orthogonal partial least squares 901:932 orthogonal partial least squares analysis (OPLS-DA) 901:951 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 8 1 theme stony 1465:1469 arg1 cultivation 1481:1491 stony epiphytic cultivation 1465:1491 stony epiphytic cultivation 1465:1491 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 2 theme live 1575:1578 arg1 cultivation 1595:1605 live tree epiphytic cultivation 1575:1605 live tree epiphytic cultivation 1575:1605 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 9 3 theme Metabolomic 1608:1618 arg1 analysis 1620:1627 Metabolomic analysis 1608:1627 Metabolomic analysis 1608:1627 Metabolomic analysis revealed that there were 185 differential metabolites among the 3 cultivation methods, with 99 of the differential metabolites being highest in the stone epiphytic cultivation. 36984829 8 4 theme epiphytic 1585:1593 arg1 cultivation 1595:1605 live tree epiphytic cultivation 1575:1605 live tree epiphytic cultivation 1575:1605 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 5 from cultivation 1481:1491 arg1 higher 1538:1543 higher 1538:1543 higher 1538:1543 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 5 from cultivation 1481:1491 arg1 content 1437:1443 the polysaccharide content 1418:1443 the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation 1418:1518 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 5 from cultivation 1481:1491 arg1 samples 1452:1458 the samples 1448:1458 the samples from stony epiphytic cultivation and greenhouse cultivation 1448:1518 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 4 6 theme greenhouse 626:635 arg1 cultivation 637:647 greenhouse cultivation 626:647 greenhouse cultivation 626:647 In order to reveal this issue, samples of the D. officinale were collected in this study through tree epiphytic cultivation, stone epiphytic cultivation, and greenhouse cultivation. 36984829 12 7 theme cultivation 2392:2402 arg1 methods 2404:2410 different cultivation methods 2382:2410 different cultivation methods 2382:2410 This study revealed the effects of different cultivation methods on the chemical composition of D. officinale and also provided a reference for establishing the quality control standards to aid its development and utilization. 36984829 7 8 theme pathway 1154:1160 arg1 analysis 1173:1180 metabolic pathway enrichment analysis 1144:1180 metabolic pathway enrichment analysis 1144:1180 The differential metabolites were taken further for metabolic pathway enrichment analysis, which was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and validated by antioxidant activity. 36984829 1 9 theme famous 177:182 arg1 plant 184:188 a famous plant 175:188 a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition) 175:284 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 1 9 theme famous 177:182 arg1 officinale 146:155 Dendrobium officinale 135:155 Dendrobium officinale Kimura et Migo 135:170 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 6 10 theme component 872:880 arg1 PCA 892:894 PCA 892:894 PCA 892:894 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 6 10 theme component 872:880 arg1 analysis 882:889 principal component analysis 862:889 principal component analysis (PCA) 862:895 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 10 11 theme vitamin 2101:2107 arg1 pathways 2120:2127 three cofactor and vitamin metabolism pathways 2082:2127 pathways 2120:2127 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 2 12 theme medicinal 291:299 arg1 properties 301:310 The medicinal properties 287:310 The medicinal properties of D. officinale 287:327 The medicinal properties of D. officinale are based on its chemical composition. 36984829 10 13 theme translation 2138:2148 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 13 theme translation 2138:2148 arg1 pathway 2150:2156 one translation pathway 2134:2156 one translation pathway 2134:2156 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 4 14 theme epiphytic 599:607 arg1 cultivation 609:619 stone epiphytic cultivation 593:619 stone epiphytic cultivation 593:619 In order to reveal this issue, samples of the D. officinale were collected in this study through tree epiphytic cultivation, stone epiphytic cultivation, and greenhouse cultivation. 36984829 10 15 theme metabolic 1946:1954 arg1 pathway 2150:2156 one translation pathway 2134:2156 one translation pathway 2134:2156 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 15 theme metabolic 1946:1954 arg1 pathway 2073:2079 one nucleotide metabolism pathway 2047:2079 one nucleotide metabolism pathway 2047:2079 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 15 theme metabolic 1946:1954 arg1 pathways 2037:2044 six amino acid metabolic pathways 2012:2044 six amino acid metabolic pathways 2012:2044 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 15 theme metabolic 1946:1954 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 15 theme metabolic 1946:1954 arg1 pathways 2002:2009 five secondary metabolite synthesis pathways 1966:2009 five secondary metabolite synthesis pathways 1966:2009 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 15 theme metabolic 1946:1954 arg1 cofactor 2088:2095 three cofactor and vitamin metabolism pathways 2082:2127 cofactor 2088:2095 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 5 16 theme sulfuric 692:699 arg1 method 706:711 phenol sulfuric acid method 685:711 phenol sulfuric acid method 685:711 Polysaccharides were determined by phenol sulfuric acid method and secondary metabolites were detected by the UPLC-MS technique. 36984829 1 17 theme high 197:200 arg1 value 212:216 a high medicinal value 195:216 a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition) 195:284 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 0 18 from Metabolites 82:92 arg1 Analysis 19:26 Metabolomics-Based Analysis 0:26 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale 0:117 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 12 19 theme quality 2508:2514 arg1 standards 2524:2532 the quality control standards 2504:2532 the quality control standards 2504:2532 This study revealed the effects of different cultivation methods on the chemical composition of D. officinale and also provided a reference for establishing the quality control standards to aid its development and utilization. 36984829 10 20 theme synthesis 1992:2000 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 20 theme synthesis 1992:2000 arg1 pathways 2002:2009 five secondary metabolite synthesis pathways 1966:2009 five secondary metabolite synthesis pathways 1966:2009 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 6 21 dep metabolomics 808:819 arg1 regards 797:803 regards 797:803 regards 797:803 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 10 22 theme information 2169:2179 arg1 processing 2181:2190 genetic information processing 2161:2190 genetic information processing 2161:2190 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 23 theme secondary 1971:1979 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 23 theme secondary 1971:1979 arg1 pathways 2002:2009 five secondary metabolite synthesis pathways 1966:2009 five secondary metabolite synthesis pathways 1966:2009 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 6 24 theme least 920:924 arg1 squares 926:932 orthogonal partial least squares 901:932 orthogonal partial least squares analysis (OPLS-DA) 901:951 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 9 25 theme cultivation 1695:1705 arg1 methods 1707:1713 the 3 cultivation methods 1689:1713 the 3 cultivation methods 1689:1713 Metabolomic analysis revealed that there were 185 differential metabolites among the 3 cultivation methods, with 99 of the differential metabolites being highest in the stone epiphytic cultivation. 36984829 10 26 theme amino 2016:2020 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 26 theme amino 2016:2020 arg1 pathways 2037:2044 six amino acid metabolic pathways 2012:2044 six amino acid metabolic pathways 2012:2044 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 11 27 theme stone 2225:2229 arg1 cultivation 2241:2251 stone epiphytic cultivation 2225:2251 stone epiphytic cultivation which had the best antioxidant activity 2225:2291 Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. 36984829 0 28 theme Strategies 68:77 arg1 Effects 35:41 the Effects 31:41 the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale 31:117 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 8 29 theme polysaccharide 1422:1435 arg1 higher 1538:1543 higher 1538:1543 higher 1538:1543 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 29 theme polysaccharide 1422:1435 arg1 content 1437:1443 the polysaccharide content 1418:1443 the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation 1418:1518 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 5 30 theme UPLC-MS 760:766 arg1 technique 768:776 the UPLC-MS technique 756:776 the UPLC-MS technique 756:776 Polysaccharides were determined by phenol sulfuric acid method and secondary metabolites were detected by the UPLC-MS technique. 36984829 11 31 theme antioxidant 2272:2282 arg1 activity 2284:2291 the best antioxidant activity 2263:2291 the best antioxidant activity 2263:2291 Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. 36984829 11 32 from cultivation 2241:2251 arg1 officinale 2209:2218 D. officinale 2206:2218 D. officinale from stone epiphytic cultivation which had the best antioxidant activity 2206:2291 Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. 36984829 10 33 theme metabolic 2027:2035 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 33 theme metabolic 2027:2035 arg1 pathways 2037:2044 six amino acid metabolic pathways 2012:2044 six amino acid metabolic pathways 2012:2044 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 0 34 theme Dendrobium 97:106 arg1 officinale 108:117 Dendrobium officinale 97:117 Dendrobium officinale 97:117 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 0 35 dep Kimura 119:124 arg1 Migo 129:132 Kimura et Migo 119:132 Kimura et Migo 119:132 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 0 35 dep Kimura 119:124 arg1 Analysis 19:26 Metabolomics-Based Analysis 0:26 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale 0:117 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 9 36 theme metabolites 1744:1754 arg1 99 1721:1722 99 1721:1722 99 1721:1722 Metabolomic analysis revealed that there were 185 differential metabolites among the 3 cultivation methods, with 99 of the differential metabolites being highest in the stone epiphytic cultivation. 36984829 9 36 theme metabolites 1744:1754 arg1 metabolites 1744:1754 the differential metabolites 1727:1754 the differential metabolites 1727:1754 Metabolomic analysis revealed that there were 185 differential metabolites among the 3 cultivation methods, with 99 of the differential metabolites being highest in the stone epiphytic cultivation. 36984829 8 37 theme samples 1452:1458 arg1 higher 1538:1543 higher 1538:1543 higher 1538:1543 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 37 theme samples 1452:1458 arg1 content 1437:1443 the polysaccharide content 1418:1443 the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation 1418:1518 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 6 38 dep values 1051:1056 arg1 >1 1058:1059 >1 1058:1059 >1 1058:1059 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 6 38 dep values 1051:1056 arg1 < 1084:1084 p < 0.05 1082:1089 p < 0.05 1082:1089 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 6 38 dep values 1051:1056 arg1 change 1067:1072 fold change >4 1062:1075 fold change >4 1062:1075 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 3 39 theme different 405:413 arg1 methods 427:433 different cultivation methods 405:433 different cultivation methods 405:433 However, there are no reports on how different cultivation methods affect its chemical composition. 36984829 12 40 theme methods 2404:2410 arg1 effects 2371:2377 the effects 2367:2377 the effects of different cultivation methods on the chemical composition of D. officinale 2367:2455 This study revealed the effects of different cultivation methods on the chemical composition of D. officinale and also provided a reference for establishing the quality control standards to aid its development and utilization. 36984829 6 41 theme fold 1062:1065 arg1 change 1067:1072 fold change >4 1062:1075 fold change >4 1062:1075 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 0 42 from Effects 35:41 arg1 Metabolites 82:92 Metabolites 82:92 Metabolites of Dendrobium officinale 82:117 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 0 43 theme Metabolomics-Based 0:17 arg1 Analysis 19:26 Metabolomics-Based Analysis 0:26 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale 0:117 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 4 44 theme D. 514:515 arg1 officinale 517:526 the D. officinale 510:526 the D. officinale 510:526 In order to reveal this issue, samples of the D. officinale were collected in this study through tree epiphytic cultivation, stone epiphytic cultivation, and greenhouse cultivation. 36984829 1 45 dep Kimura 157:162 arg1 et 164:165 Kimura et Migo 157:170 Dendrobium officinale Kimura et Migo 135:170 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 1 45 dep Kimura 157:162 arg1 Migo 167:170 Migo 167:170 Migo 167:170 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 6 46 used used 825:828 arg2 we 822:823 we 822:823 we 822:823 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 6 47 theme principal 862:870 arg1 PCA 892:894 PCA 892:894 PCA 892:894 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 6 47 theme principal 862:870 arg1 analysis 882:889 principal component analysis 862:889 principal component analysis (PCA) 862:895 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 6 48 theme projection 1040:1049 arg1 values 1051:1056 variable importance projection values >1, fold change >4, and p < 0.05 1020:1089 variable importance projection values >1, fold change >4, and p < 0.05 1020:1089 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 9 49 theme epiphytic 1783:1791 arg1 cultivation 1793:1803 the stone epiphytic cultivation 1773:1803 the stone epiphytic cultivation 1773:1803 Metabolomic analysis revealed that there were 185 differential metabolites among the 3 cultivation methods, with 99 of the differential metabolites being highest in the stone epiphytic cultivation. 36984829 8 50 theme greenhouse 1497:1506 arg1 cultivation 1508:1518 greenhouse cultivation 1497:1518 greenhouse cultivation 1497:1518 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 0 51 theme Effects 35:41 arg1 Analysis 19:26 Metabolomics-Based Analysis 0:26 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale 0:117 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 6 52 theme variable 1020:1027 arg1 values 1051:1056 variable importance projection values >1, fold change >4, and p < 0.05 1020:1089 variable importance projection values >1, fold change >4, and p < 0.05 1020:1089 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 12 53 theme D. 2443:2444 arg1 officinale 2446:2455 D. officinale 2443:2455 D. officinale 2443:2455 This study revealed the effects of different cultivation methods on the chemical composition of D. officinale and also provided a reference for establishing the quality control standards to aid its development and utilization. 36984829 0 54 theme Different 46:54 arg1 Strategies 68:77 Different Cultivation Strategies 46:77 Different Cultivation Strategies 46:77 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 10 55 theme analysis 1854:1861 arg1 results 1810:1816 The results 1806:1816 The results of the metabolic pathway enrichment analysis 1806:1861 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 8 56 theme ChP 1374:1376 arg1 standards 1357:1365 the standards 1353:1365 the standards of the ChP (2020 edition) 1353:1391 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 2 57 theme D. 315:316 arg1 officinale 318:327 D. officinale 315:327 D. officinale 315:327 The medicinal properties of D. officinale are based on its chemical composition. 36984829 7 58 theme Genomes 1238:1244 arg1 database 1253:1260 Genomes (KEGG) database 1238:1260 Genomes (KEGG) database 1238:1260 The differential metabolites were taken further for metabolic pathway enrichment analysis, which was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and validated by antioxidant activity. 36984829 10 59 theme nucleotide 2051:2060 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 59 theme nucleotide 2051:2060 arg1 pathway 2073:2079 one nucleotide metabolism pathway 2047:2079 one nucleotide metabolism pathway 2047:2079 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 4 60 theme tree 565:568 arg1 cultivation 580:590 tree epiphytic cultivation 565:590 tree epiphytic cultivation 565:590 In order to reveal this issue, samples of the D. officinale were collected in this study through tree epiphytic cultivation, stone epiphytic cultivation, and greenhouse cultivation. 36984829 10 61 theme pathway 1835:1841 arg1 analysis 1854:1861 the metabolic pathway enrichment analysis 1821:1861 the metabolic pathway enrichment analysis 1821:1861 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 2 62 theme chemical 346:353 arg1 composition 355:365 its chemical composition 342:365 its chemical composition 342:365 The medicinal properties of D. officinale are based on its chemical composition. 36984829 0 63 theme Cultivation 56:66 arg1 Strategies 68:77 Different Cultivation Strategies 46:77 Different Cultivation Strategies 46:77 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 6 64 theme partial 912:918 arg1 squares 926:932 orthogonal partial least squares 901:932 orthogonal partial least squares analysis (OPLS-DA) 901:951 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 10 65 theme different 1879:1887 arg1 strategies 1901:1910 the different cultivation strategies 1875:1910 the different cultivation strategies 1875:1910 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 8 66 from cultivation 1508:1518 arg1 higher 1538:1543 higher 1538:1543 higher 1538:1543 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 66 from cultivation 1508:1518 arg1 content 1437:1443 the polysaccharide content 1418:1443 the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation 1418:1518 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 66 from cultivation 1508:1518 arg1 samples 1452:1458 the samples 1448:1458 the samples from stony epiphytic cultivation and greenhouse cultivation 1448:1518 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 12 67 theme different 2382:2390 arg1 methods 2404:2410 different cultivation methods 2382:2410 different cultivation methods 2382:2410 This study revealed the effects of different cultivation methods on the chemical composition of D. officinale and also provided a reference for establishing the quality control standards to aid its development and utilization. 36984829 1 68 theme Chinese 249:255 arg1 Edition 277:283 2020 Edition 272:283 2020 Edition 272:283 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 1 68 theme Chinese 249:255 arg1 Pharmacopoeia 257:269 the Chinese Pharmacopoeia 245:269 the Chinese Pharmacopoeia (2020 Edition) 245:284 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 8 69 theme tree 1580:1583 arg1 cultivation 1595:1605 live tree epiphytic cultivation 1575:1605 live tree epiphytic cultivation 1575:1605 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 10 70 theme metabolism 2109:2118 arg1 pathways 2120:2127 three cofactor and vitamin metabolism pathways 2082:2127 pathways 2120:2127 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 11 71 theme differential 2311:2322 arg1 production 2335:2344 differential metabolite production 2311:2344 differential metabolite production 2311:2344 Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. 36984829 5 72 theme phenol 685:690 arg1 method 706:711 phenol sulfuric acid method 685:711 phenol sulfuric acid method 685:711 Polysaccharides were determined by phenol sulfuric acid method and secondary metabolites were detected by the UPLC-MS technique. 36984829 9 73 theme differential 1658:1669 arg1 metabolites 1671:1681 185 differential metabolites 1654:1681 185 differential metabolites among the 3 cultivation methods 1654:1713 Metabolomic analysis revealed that there were 185 differential metabolites among the 3 cultivation methods, with 99 of the differential metabolites being highest in the stone epiphytic cultivation. 36984829 12 74 theme control 2516:2522 arg1 standards 2524:2532 the quality control standards 2504:2532 the quality control standards 2504:2532 This study revealed the effects of different cultivation methods on the chemical composition of D. officinale and also provided a reference for establishing the quality control standards to aid its development and utilization. 36984829 4 75 theme stone 593:597 arg1 cultivation 609:619 stone epiphytic cultivation 593:619 stone epiphytic cultivation 593:619 In order to reveal this issue, samples of the D. officinale were collected in this study through tree epiphytic cultivation, stone epiphytic cultivation, and greenhouse cultivation. 36984829 10 76 theme carbohydrate 1933:1944 arg1 pathway 2150:2156 one translation pathway 2134:2156 one translation pathway 2134:2156 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 76 theme carbohydrate 1933:1944 arg1 pathway 2073:2079 one nucleotide metabolism pathway 2047:2079 one nucleotide metabolism pathway 2047:2079 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 76 theme carbohydrate 1933:1944 arg1 pathways 2037:2044 six amino acid metabolic pathways 2012:2044 six amino acid metabolic pathways 2012:2044 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 76 theme carbohydrate 1933:1944 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 76 theme carbohydrate 1933:1944 arg1 pathways 2002:2009 five secondary metabolite synthesis pathways 1966:2009 five secondary metabolite synthesis pathways 1966:2009 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 76 theme carbohydrate 1933:1944 arg1 cofactor 2088:2095 three cofactor and vitamin metabolism pathways 2082:2127 cofactor 2088:2095 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 5 77 theme acid 701:704 arg1 method 706:711 phenol sulfuric acid method 685:711 phenol sulfuric acid method 685:711 Polysaccharides were determined by phenol sulfuric acid method and secondary metabolites were detected by the UPLC-MS technique. 36984829 1 78 theme medicinal 202:210 arg1 value 212:216 a high medicinal value 195:216 a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition) 195:284 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 10 79 theme metabolite 1981:1990 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 79 theme metabolite 1981:1990 arg1 pathways 2002:2009 five secondary metabolite synthesis pathways 1966:2009 five secondary metabolite synthesis pathways 1966:2009 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 6 80 theme squares 926:932 arg1 analysis 934:941 orthogonal partial least squares analysis 901:941 orthogonal partial least squares analysis (OPLS-DA) 901:951 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 6 80 theme squares 926:932 arg1 OPLS-DA 944:950 OPLS-DA 944:950 OPLS-DA 944:950 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 10 81 theme genetic 2161:2167 arg1 processing 2181:2190 genetic information processing 2161:2190 genetic information processing 2161:2190 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 1 82 theme Dendrobium 135:144 arg1 plant 184:188 a famous plant 175:188 a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition) 175:284 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 1 82 theme Dendrobium 135:144 arg1 officinale 146:155 Dendrobium officinale 135:155 Dendrobium officinale Kimura et Migo 135:170 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 11 83 theme metabolite 2324:2333 arg1 production 2335:2344 differential metabolite production 2311:2344 differential metabolite production 2311:2344 Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. 36984829 11 84 theme epiphytic 2231:2239 arg1 cultivation 2241:2251 stone epiphytic cultivation 2225:2251 stone epiphytic cultivation which had the best antioxidant activity 2225:2291 Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. 36984829 12 85 theme chemical 2419:2426 arg1 composition 2428:2438 the chemical composition 2415:2438 the chemical composition of D. officinale 2415:2455 This study revealed the effects of different cultivation methods on the chemical composition of D. officinale and also provided a reference for establishing the quality control standards to aid its development and utilization. 36984829 5 86 theme secondary 717:725 arg1 metabolites 727:737 secondary metabolites 717:737 secondary metabolites 717:737 Polysaccharides were determined by phenol sulfuric acid method and secondary metabolites were detected by the UPLC-MS technique. 36984829 0 87 from Analysis 19:26 arg1 Metabolites 82:92 Metabolites 82:92 Metabolites of Dendrobium officinale 82:117 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 12 88 from effects 2371:2377 arg1 composition 2428:2438 the chemical composition 2415:2438 the chemical composition of D. officinale 2415:2455 This study revealed the effects of different cultivation methods on the chemical composition of D. officinale and also provided a reference for establishing the quality control standards to aid its development and utilization. 36984829 0 89 theme officinale 108:117 arg1 Metabolites 82:92 Metabolites 82:92 Metabolites of Dendrobium officinale 82:117 Metabolomics-Based Analysis of the Effects of Different Cultivation Strategies on Metabolites of Dendrobium officinale Kimura et Migo. 36984829 6 90 theme differential 967:978 arg1 metabolites 980:990 differential metabolites 967:990 differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05 967:1089 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 9 91 theme differential 1731:1742 arg1 metabolites 1744:1754 the differential metabolites 1727:1754 the differential metabolites 1727:1754 Metabolomic analysis revealed that there were 185 differential metabolites among the 3 cultivation methods, with 99 of the differential metabolites being highest in the stone epiphytic cultivation. 36984829 1 92 dep officinale 146:155 arg1 Kimura 157:162 Kimura 157:162 Kimura 157:162 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 10 93 theme acid 2022:2025 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 93 theme acid 2022:2025 arg1 pathways 2037:2044 six amino acid metabolic pathways 2012:2044 six amino acid metabolic pathways 2012:2044 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 7 94 theme enrichment 1162:1171 arg1 analysis 1173:1180 metabolic pathway enrichment analysis 1144:1180 metabolic pathway enrichment analysis 1144:1180 The differential metabolites were taken further for metabolic pathway enrichment analysis, which was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and validated by antioxidant activity. 36984829 7 95 theme antioxidant 1280:1290 arg1 activity 1292:1299 antioxidant activity 1280:1299 antioxidant activity 1280:1299 The differential metabolites were taken further for metabolic pathway enrichment analysis, which was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and validated by antioxidant activity. 36984829 8 96 theme epiphytic 1471:1479 arg1 cultivation 1481:1491 stony epiphytic cultivation 1465:1491 stony epiphytic cultivation 1465:1491 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 97 from cultivation 1595:1605 arg1 samples 1562:1568 the samples 1558:1568 the samples from live tree epiphytic cultivation 1558:1605 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 3 98 theme cultivation 415:425 arg1 methods 427:433 different cultivation methods 405:433 different cultivation methods 405:433 However, there are no reports on how different cultivation methods affect its chemical composition. 36984829 7 99 theme metabolic 1144:1152 arg1 analysis 1173:1180 metabolic pathway enrichment analysis 1144:1180 metabolic pathway enrichment analysis 1144:1180 The differential metabolites were taken further for metabolic pathway enrichment analysis, which was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and validated by antioxidant activity. 36984829 4 100 theme officinale 517:526 arg1 samples 499:505 samples 499:505 samples of the D. officinale 499:526 In order to reveal this issue, samples of the D. officinale were collected in this study through tree epiphytic cultivation, stone epiphytic cultivation, and greenhouse cultivation. 36984829 8 101 from content 1437:1443 arg1 cultivation 1481:1491 stony epiphytic cultivation 1465:1491 stony epiphytic cultivation 1465:1491 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 101 from content 1437:1443 arg1 cultivation 1508:1518 greenhouse cultivation 1497:1518 greenhouse cultivation 1497:1518 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 6 102 theme values 1051:1056 arg1 conditions 1006:1015 the conditions 1002:1015 the conditions of variable importance projection values >1, fold change >4, and p < 0.05 1002:1089 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 9 103 theme stone 1777:1781 arg1 cultivation 1793:1803 the stone epiphytic cultivation 1773:1803 the stone epiphytic cultivation 1773:1803 Metabolomic analysis revealed that there were 185 differential metabolites among the 3 cultivation methods, with 99 of the differential metabolites being highest in the stone epiphytic cultivation. 36984829 10 104 theme metabolic 1825:1833 arg1 analysis 1854:1861 the metabolic pathway enrichment analysis 1821:1861 the metabolic pathway enrichment analysis 1821:1861 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 8 105 theme samples 1332:1338 arg1 samples 1332:1338 samples 1332:1338 samples 1332:1338 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 8 105 theme samples 1332:1338 arg1 groups 1322:1327 the three groups 1312:1327 the three groups of samples 1312:1338 Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. 36984829 3 106 theme chemical 446:453 arg1 composition 455:465 its chemical composition 442:465 its chemical composition 442:465 However, there are no reports on how different cultivation methods affect its chemical composition. 36984829 6 107 theme importance 1029:1038 arg1 values 1051:1056 variable importance projection values >1, fold change >4, and p < 0.05 1020:1089 variable importance projection values >1, fold change >4, and p < 0.05 1020:1089 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 11 108 theme D. 2206:2207 arg1 officinale 2209:2218 D. officinale 2206:2218 D. officinale from stone epiphytic cultivation which had the best antioxidant activity 2206:2291 Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. 36984829 12 109 theme officinale 2446:2455 arg1 composition 2428:2438 the chemical composition 2415:2438 the chemical composition of D. officinale 2415:2455 This study revealed the effects of different cultivation methods on the chemical composition of D. officinale and also provided a reference for establishing the quality control standards to aid its development and utilization. 36984829 7 110 theme differential 1096:1107 arg1 metabolites 1109:1119 The differential metabolites 1092:1119 The differential metabolites 1092:1119 The differential metabolites were taken further for metabolic pathway enrichment analysis, which was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and validated by antioxidant activity. 36984829 1 111 with plant 184:188 arg1 value 212:216 a high medicinal value 195:216 a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition) 195:284 Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). 36984829 6 112 theme multivariate 830:841 arg1 analysis 934:941 orthogonal partial least squares analysis 901:941 orthogonal partial least squares analysis (OPLS-DA) 901:951 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 6 112 theme multivariate 830:841 arg1 analyses 843:850 multivariate analyses 830:850 multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) 830:951 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 6 112 theme multivariate 830:841 arg1 analysis 882:889 principal component analysis 862:889 principal component analysis (PCA) 862:895 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 2 113 theme officinale 318:327 arg1 properties 301:310 The medicinal properties 287:310 The medicinal properties of D. officinale 287:327 The medicinal properties of D. officinale are based on its chemical composition. 36984829 10 114 theme metabolism 2062:2071 arg1 pathways 1956:1963 four carbohydrate metabolic pathways 1928:1963 four carbohydrate metabolic pathways 1928:1963 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 10 114 theme metabolism 2062:2071 arg1 pathway 2073:2079 one nucleotide metabolism pathway 2047:2079 one nucleotide metabolism pathway 2047:2079 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 4 115 theme epiphytic 570:578 arg1 cultivation 580:590 tree epiphytic cultivation 565:590 tree epiphytic cultivation 565:590 In order to reveal this issue, samples of the D. officinale were collected in this study through tree epiphytic cultivation, stone epiphytic cultivation, and greenhouse cultivation. 36984829 11 116 contain had 2259:2261 arg1 cultivation 2241:2251 stone epiphytic cultivation 2225:2251 stone epiphytic cultivation which had the best antioxidant activity 2225:2291 Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. 36984829 11 116 contain had 2259:2261 arg2 activity 2284:2291 the best antioxidant activity 2263:2291 the best antioxidant activity 2263:2291 Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. 36984829 10 117 theme enrichment 1843:1852 arg1 analysis 1854:1861 the metabolic pathway enrichment analysis 1821:1861 the metabolic pathway enrichment analysis 1821:1861 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 36984829 11 118 theme best 2267:2270 arg1 activity 2284:2291 the best antioxidant activity 2263:2291 the best antioxidant activity 2263:2291 Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. 36984829 6 119 theme p 1082:1082 arg1 < 1084:1084 p < 0.05 1082:1089 p < 0.05 1082:1089 In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. 36984829 10 120 theme cultivation 1889:1899 arg1 strategies 1901:1910 the different cultivation strategies 1875:1910 the different cultivation strategies 1875:1910 The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. 37296446 9 0 from phase 1394:1398 arg1 diverse 1372:1378 diverse 1372:1378 diverse 1372:1378 We have observed an evolution of its bacteriome, which is diverse at the larval phase, substantially diminished in pupae, greater in the teneral adult phase, and similar to that of the larval stage in mature adults. 37296446 14 1 theme Pseudomonas 2620:2630 arg1 group 2644:2648 Pseudomonas and Erwinia group 2620:2648 Pseudomonas and Erwinia group 2620:2648 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 1 2 from forests 221:227 arg1 Europe 232:237 Europe 232:237 Europe 232:237 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 13 3 theme typographus 2516:2526 arg1 beetles 2528:2534 I. typographus beetles 2513:2534 I. typographus beetles 2513:2534 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 15 4 theme more 2925:2928 arg1 insights 2930:2937 more insights 2925:2937 more insights into the bacteriome capacity to be beneficial to the beetle 2925:2997 Future studies involving bacterial-insect interactions or analysing other potential roles would provide more insights into the bacteriome capacity to be beneficial to the beetle. 37296446 1 5 from pest 206:209 arg1 Europe 232:237 Europe 232:237 Europe 232:237 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 3 6 theme beetle 518:523 arg1 ecology 525:531 the beetle ecology 514:531 the beetle ecology 514:531 About the bacteriome, there still are many uncertainties regarding the taxonomical composition, insect-bacteriome interactions, and their potential roles in the beetle ecology. 37296446 14 7 theme lower 2804:2808 arg1 frequency 2810:2818 a lower frequency 2802:2818 a lower frequency 2802:2818 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 8 8 theme taxonomical 1199:1209 arg1 analysis 1211:1218 a taxonomical analysis 1197:1218 a taxonomical analysis of the bacteriome associated with the I. typographus beetle during its different life stages 1197:1311 Using culture-dependent and -independent techniques, we present a taxonomical analysis of the bacteriome associated with the I. typographus beetle during its different life stages. 37296446 3 9 from composition 440:450 arg1 ecology 525:531 the beetle ecology 514:531 the beetle ecology 514:531 About the bacteriome, there still are many uncertainties regarding the taxonomical composition, insect-bacteriome interactions, and their potential roles in the beetle ecology. 37296446 2 10 theme other 247:251 arg1 animals 253:259 other animals 247:259 other animals 247:259 As for other animals, it has been proposed that the microbiome plays important roles in the biology of bark beetles. 37296446 8 11 theme culture-dependent 1139:1155 arg1 techniques 1174:1183 culture-dependent and -independent techniques 1139:1183 culture-dependent and -independent techniques 1139:1183 Using culture-dependent and -independent techniques, we present a taxonomical analysis of the bacteriome associated with the I. typographus beetle during its different life stages. 37296446 6 12 theme complex 844:850 arg1 polysaccharides 852:866 one or more complex polysaccharides 832:866 one or more complex polysaccharides 832:866 All strains showed the capacity to hydrolyse one or more complex polysaccharides into simpler molecules, which may provide an additional carbon source to its host. 37296446 4 13 theme bacteria 642:649 arg1 composition 601:611 taxonomical composition 589:611 taxonomical composition 589:611 Here, we aim to deep into the ecological functions and taxonomical composition of I. typographus associated bacteria. 37296446 4 13 theme bacteria 642:649 arg1 functions 575:583 ecological functions 564:583 ecological functions 564:583 Here, we aim to deep into the ecological functions and taxonomical composition of I. typographus associated bacteria. 37296446 11 14 theme additional 1968:1977 arg1 sources 2002:2008 additional and assimilable carbon sources 1968:2008 additional and assimilable carbon sources for the beetle 1968:2023 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 8 15 theme -independent 1161:1172 arg1 techniques 1174:1183 culture-dependent and -independent techniques 1139:1183 culture-dependent and -independent techniques 1139:1183 Using culture-dependent and -independent techniques, we present a taxonomical analysis of the bacteriome associated with the I. typographus beetle during its different life stages. 37296446 11 16 theme carbon 1995:2000 arg1 sources 2002:2008 additional and assimilable carbon sources 1968:2008 additional and assimilable carbon sources for the beetle 1968:2023 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 9 17 theme larval 1387:1392 arg1 phase 1394:1398 the larval phase 1383:1398 the larval phase 1383:1398 We have observed an evolution of its bacteriome, which is diverse at the larval phase, substantially diminished in pupae, greater in the teneral adult phase, and similar to that of the larval stage in mature adults. 37296446 15 18 theme Future 2821:2826 arg1 studies 2828:2834 Future studies 2821:2834 Future studies involving bacterial-insect interactions or analysing other potential roles 2821:2909 Future studies involving bacterial-insect interactions or analysing other potential roles would provide more insights into the bacteriome capacity to be beneficial to the beetle. 37296446 4 19 theme taxonomical 589:599 arg1 composition 601:611 taxonomical composition 589:611 taxonomical composition 589:611 Here, we aim to deep into the ecological functions and taxonomical composition of I. typographus associated bacteria. 37296446 13 20 theme Pseudoxanthomonas 2362:2378 arg1 genus 2380:2384 Pseudoxanthomonas genus 2362:2384 Pseudoxanthomonas genus 2362:2384 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 5 21 theme metabolic 676:684 arg1 potential 686:694 the metabolic potential 672:694 the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles 672:784 RESULTS We assessed the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles. 37296446 13 22 theme taxonomical 2241:2251 arg1 analysis 2253:2260 Our taxonomical analysis 2237:2260 Our taxonomical analysis 2237:2260 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 11 23 theme typographus 1882:1892 arg1 beetle 1894:1899 I. typographus beetle 1879:1899 I. typographus beetle 1879:1899 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 6 24 theme additional 913:922 arg1 source 931:936 an additional carbon source 910:936 an additional carbon source 910:936 All strains showed the capacity to hydrolyse one or more complex polysaccharides into simpler molecules, which may provide an additional carbon source to its host. 37296446 14 25 theme interesting 2750:2760 arg1 capacities 2772:2781 interesting metabolic capacities 2750:2781 interesting metabolic capacities 2750:2781 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 8 26 theme I. 1258:1259 arg1 beetle 1273:1278 the I. typographus beetle 1254:1278 the I. typographus beetle during its different life stages 1254:1311 Using culture-dependent and -independent techniques, we present a taxonomical analysis of the bacteriome associated with the I. typographus beetle during its different life stages. 37296446 4 27 dep functions 575:583 arg1 the 560:562 the 560:562 the 560:562 Here, we aim to deep into the ecological functions and taxonomical composition of I. typographus associated bacteria. 37296446 9 28 from stage 1506:1510 arg1 adults 1522:1527 mature adults 1515:1527 mature adults 1515:1527 We have observed an evolution of its bacteriome, which is diverse at the larval phase, substantially diminished in pupae, greater in the teneral adult phase, and similar to that of the larval stage in mature adults. 37296446 13 29 theme Erwiniaceae 2426:2436 arg1 group 2459:2463 the Erwiniaceae and Enterobacterales group 2422:2463 the Erwiniaceae and Enterobacterales group 2422:2463 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 11 30 theme metabolic 1910:1918 arg1 potential 1920:1928 the metabolic potential 1906:1928 the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens 1906:2066 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 9 31 theme teneral 1451:1457 arg1 phase 1465:1469 the teneral adult phase 1447:1469 the teneral adult phase 1447:1469 We have observed an evolution of its bacteriome, which is diverse at the larval phase, substantially diminished in pupae, greater in the teneral adult phase, and similar to that of the larval stage in mature adults. 37296446 11 32 dep increase 1933:1940 arg1 antagonizing 2033:2044 antagonizing 2033:2044 antagonizing fungi entomopathogens 2033:2066 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 11 32 dep increase 1933:1940 arg1 proving 1960:1966 proving 1960:1966 proving additional and assimilable carbon sources for the beetle 1960:2023 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 15 33 theme potential 2895:2903 arg1 roles 2905:2909 other potential roles 2889:2909 other potential roles 2889:2909 Future studies involving bacterial-insect interactions or analysing other potential roles would provide more insights into the bacteriome capacity to be beneficial to the beetle. 37296446 10 34 theme core 1733:1736 arg1 microbiome 1738:1747 the core microbiome 1729:1747 the core microbiome 1729:1747 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 15 35 dep studies 2828:2834 arg1 involving 2836:2844 involving 2836:2844 involving bacterial-insect interactions 2836:2874 Future studies involving bacterial-insect interactions or analysing other potential roles would provide more insights into the bacteriome capacity to be beneficial to the beetle. 37296446 15 35 dep studies 2828:2834 arg1 analysing 2879:2887 analysing 2879:2887 analysing other potential roles 2879:2909 Future studies involving bacterial-insect interactions or analysing other potential roles would provide more insights into the bacteriome capacity to be beneficial to the beetle. 37296446 12 36 theme strongest 2206:2214 arg1 activity 2227:2234 strongest antifungal activity 2206:2234 strongest antifungal activity 2206:2234 Furthermore, we observed that isolates from adult beetles are more likely to have these capacities but those obtained from larvae showed strongest antifungal activity. 37296446 8 37 theme life 1301:1304 arg1 stages 1306:1311 its different life stages 1287:1311 its different life stages 1287:1311 Using culture-dependent and -independent techniques, we present a taxonomical analysis of the bacteriome associated with the I. typographus beetle during its different life stages. 37296446 0 38 theme unexplored 68:77 arg1 diversity 79:87 unexplored diversity 68:87 unexplored diversity potentially beneficial to the host 68:122 New insight into the bark beetle ips typographus bacteriome reveals unexplored diversity potentially beneficial to the host. 37296446 1 39 theme spruce 162:167 arg1 beetle 174:179 European spruce bark beetle 153:179 European spruce bark beetle 153:179 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 1 39 theme spruce 162:167 arg1 typographus 140:150 BACKGROUND Ips typographus 125:150 BACKGROUND Ips typographus (European spruce bark beetle) 125:180 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 5 40 theme collection 701:710 arg1 potential 686:694 the metabolic potential 672:694 the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles 672:784 RESULTS We assessed the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles. 37296446 11 41 theme beetle 1942:1947 arg1 fitness 1949:1955 beetle fitness 1942:1955 beetle fitness 1942:1955 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 13 42 theme putative 2391:2398 arg1 taxa 2404:2407 putative new taxa 2391:2407 putative new taxa 2391:2407 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 1 43 theme Ips 136:138 arg1 beetle 174:179 European spruce bark beetle 153:179 European spruce bark beetle 153:179 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 1 43 theme Ips 136:138 arg1 typographus 140:150 BACKGROUND Ips typographus 125:150 BACKGROUND Ips typographus (European spruce bark beetle) 125:180 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 1 43 theme Ips 136:138 arg1 pest 206:209 the most destructive pest 185:209 the most destructive pest of spruce forests in Europe 185:237 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 10 44 theme Erwiniaceae 1577:1587 arg1 Pseudoxanthomonas 1605:1621 Pseudoxanthomonas 1605:1621 Pseudoxanthomonas 1605:1621 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 10 44 theme Erwiniaceae 1577:1587 arg1 genera 1639:1644 Pseudomonas genera 1627:1644 Pseudomonas genera 1627:1644 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 10 44 theme Erwiniaceae 1577:1587 arg1 family 1589:1594 the Erwiniaceae family 1573:1594 the Erwiniaceae family 1573:1594 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 5 45 theme isolates 715:722 arg1 collection 701:710 a collection 699:710 a collection of isolates obtained from different life stages of I. typographus beetles 699:784 RESULTS We assessed the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles. 37296446 13 46 theme beetles 2528:2534 arg1 bacteriome 2499:2508 the bacteriome 2495:2508 the bacteriome of I. typographus beetles 2495:2534 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 2 47 theme bark 343:346 arg1 beetles 348:354 bark beetles 343:354 bark beetles 343:354 As for other animals, it has been proposed that the microbiome plays important roles in the biology of bark beetles. 37296446 0 48 theme New 0:2 arg1 insight 4:10 New insight 0:10 New insight into the bark beetle ips typographus bacteriome 0:58 New insight into the bark beetle ips typographus bacteriome reveals unexplored diversity potentially beneficial to the host. 37296446 9 49 theme larval 1499:1504 arg1 stage 1506:1510 the larval stage 1495:1510 the larval stage in mature adults 1495:1527 We have observed an evolution of its bacteriome, which is diverse at the larval phase, substantially diminished in pupae, greater in the teneral adult phase, and similar to that of the larval stage in mature adults. 37296446 11 50 theme beetle 1894:1899 arg1 bacteriome 1865:1874 the bacteriome 1861:1874 the bacteriome of I. typographus beetle 1861:1899 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 11 51 dep CONCLUSION 1808:1817 arg1 indicate 1831:1838 indicate 1831:1838 indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens 1831:2066 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 7 52 theme pathogenic 1114:1123 arg1 threat 1125:1130 this pathogenic threat 1109:1130 this pathogenic threat 1109:1130 Also, 83.9% of the strains isolated showed antagonistic effect against one or more entomopathogenic fungi, which could assist the beetle in its fight against this pathogenic threat. 37296446 12 53 theme adult 2113:2117 arg1 beetles 2119:2125 adult beetles 2113:2125 adult beetles 2113:2125 Furthermore, we observed that isolates from adult beetles are more likely to have these capacities but those obtained from larvae showed strongest antifungal activity. 37296446 0 54 theme bark 21:24 arg1 bacteriome 49:58 the bark beetle ips typographus bacteriome 17:58 the bark beetle ips typographus bacteriome 17:58 New insight into the bark beetle ips typographus bacteriome reveals unexplored diversity potentially beneficial to the host. 37296446 13 55 theme typographi 2332:2341 arg1 species 2343:2349 Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species 2274:2349 Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species 2274:2349 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 3 56 theme insect-bacteriome 453:469 arg1 interactions 471:482 insect-bacteriome interactions 453:482 insect-bacteriome interactions 453:482 About the bacteriome, there still are many uncertainties regarding the taxonomical composition, insect-bacteriome interactions, and their potential roles in the beetle ecology. 37296446 5 57 theme typographus 766:776 arg1 beetles 778:784 I. typographus beetles 763:784 I. typographus beetles 763:784 RESULTS We assessed the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles. 37296446 14 58 located present 2791:2797 arg1 frequency 2810:2818 a lower frequency 2802:2818 a lower frequency 2802:2818 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 14 58 located present 2791:2797 arg2 Curtobacterium 2682:2695 Curtobacterium 2682:2695 Curtobacterium 2682:2695 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 7 59 from beetle 1081:1086 arg1 fight 1095:1099 its fight 1091:1099 its fight against this pathogenic threat 1091:1130 Also, 83.9% of the strains isolated showed antagonistic effect against one or more entomopathogenic fungi, which could assist the beetle in its fight against this pathogenic threat. 37296446 12 60 from beetles 2119:2125 arg1 isolates 2099:2106 isolates 2099:2106 isolates from adult beetles 2099:2125 Furthermore, we observed that isolates from adult beetles are more likely to have these capacities but those obtained from larvae showed strongest antifungal activity. 37296446 13 61 theme bohemica 2306:2313 arg1 species 2343:2349 Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species 2274:2349 Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species 2274:2349 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 1 62 theme forests 221:227 arg1 typographus 140:150 BACKGROUND Ips typographus 125:150 BACKGROUND Ips typographus (European spruce bark beetle) 125:180 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 1 62 theme forests 221:227 arg1 pest 206:209 the most destructive pest 185:209 the most destructive pest of spruce forests in Europe 185:237 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 5 63 theme I. 763:764 arg1 beetles 778:784 I. typographus beetles 763:784 I. typographus beetles 763:784 RESULTS We assessed the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles. 37296446 11 64 contain have 1901:1904 arg1 isolates 1845:1852 isolates 1845:1852 isolates within the bacteriome of I. typographus beetle 1845:1899 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 11 64 contain have 1901:1904 arg2 potential 1920:1928 the metabolic potential 1906:1928 the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens 1906:2066 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 4 65 theme ecological 564:573 arg1 functions 575:583 ecological functions 564:583 ecological functions 564:583 Here, we aim to deep into the ecological functions and taxonomical composition of I. typographus associated bacteria. 37296446 11 66 theme fungi 2046:2050 arg1 entomopathogens 2052:2066 fungi entomopathogens 2046:2066 fungi entomopathogens 2046:2066 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 13 67 theme I. 2513:2514 arg1 beetles 2528:2534 I. typographus beetles 2513:2534 I. typographus beetles 2513:2534 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 6 68 theme simpler 873:879 arg1 molecules 881:889 simpler molecules 873:889 simpler molecules 873:889 All strains showed the capacity to hydrolyse one or more complex polysaccharides into simpler molecules, which may provide an additional carbon source to its host. 37296446 15 69 theme other 2889:2893 arg1 roles 2905:2909 other potential roles 2889:2909 other potential roles 2889:2909 Future studies involving bacterial-insect interactions or analysing other potential roles would provide more insights into the bacteriome capacity to be beneficial to the beetle. 37296446 2 70 theme important 309:317 arg1 roles 319:323 important roles 309:323 important roles 309:323 As for other animals, it has been proposed that the microbiome plays important roles in the biology of bark beetles. 37296446 14 71 from frequency 2810:2818 arg1 present 2791:2797 present 2791:2797 present 2791:2797 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 10 72 theme undescribed 1661:1671 arg1 genus 1673:1677 an undescribed genus 1658:1677 an undescribed genus within the Enterobactereaceae family 1658:1714 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 10 72 theme undescribed 1661:1671 arg1 part 1721:1724 part 1721:1724 part of the core microbiome 1721:1747 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 10 72 theme undescribed 1661:1671 arg1 taxa 1555:1558 taxa 1555:1558 taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera 1555:1644 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 1 73 theme bark 169:172 arg1 beetle 174:179 European spruce bark beetle 153:179 European spruce bark beetle 153:179 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 1 73 theme bark 169:172 arg1 typographus 140:150 BACKGROUND Ips typographus 125:150 BACKGROUND Ips typographus (European spruce bark beetle) 125:180 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 0 74 theme ips 33:35 arg1 bacteriome 49:58 the bark beetle ips typographus bacteriome 17:58 the bark beetle ips typographus bacteriome 17:58 New insight into the bark beetle ips typographus bacteriome reveals unexplored diversity potentially beneficial to the host. 37296446 13 75 dep along 2351:2355 arg1 with 2357:2360 with 2357:2360 with 2357:2360 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 5 76 theme life 748:751 arg1 stages 753:758 different life stages 738:758 different life stages of I. typographus beetles 738:784 RESULTS We assessed the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles. 37296446 7 77 theme entomopathogenic 1034:1049 arg1 fungi 1051:1055 one or more entomopathogenic fungi 1022:1055 one or more entomopathogenic fungi 1022:1055 Also, 83.9% of the strains isolated showed antagonistic effect against one or more entomopathogenic fungi, which could assist the beetle in its fight against this pathogenic threat. 37296446 13 78 theme typographi 2282:2291 arg1 species 2343:2349 Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species 2274:2349 Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species 2274:2349 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 15 79 theme bacterial-insect 2846:2861 arg1 interactions 2863:2874 bacterial-insect interactions 2846:2874 bacterial-insect interactions 2846:2874 Future studies involving bacterial-insect interactions or analysing other potential roles would provide more insights into the bacteriome capacity to be beneficial to the beetle. 37296446 4 80 theme associated 631:640 arg1 bacteria 642:649 I. typographus associated bacteria 616:649 I. typographus associated bacteria 616:649 Here, we aim to deep into the ecological functions and taxonomical composition of I. typographus associated bacteria. 37296446 3 81 from interactions 471:482 arg1 ecology 525:531 the beetle ecology 514:531 the beetle ecology 514:531 About the bacteriome, there still are many uncertainties regarding the taxonomical composition, insect-bacteriome interactions, and their potential roles in the beetle ecology. 37296446 10 82 theme Enterobactereaceae 1690:1707 arg1 family 1709:1714 the Enterobactereaceae family 1686:1714 the Enterobactereaceae family 1686:1714 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 13 83 located present 2480:2486 arg2 taxa 2404:2407 putative new taxa 2391:2407 putative new taxa 2391:2407 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 13 83 located present 2480:2486 arg2 species 2343:2349 Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species 2274:2349 Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species 2274:2349 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 13 83 located present 2480:2486 arg1 bacteriome 2499:2508 the bacteriome 2495:2508 the bacteriome of I. typographus beetles 2495:2534 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 13 83 located present 2480:2486 arg2 genus 2380:2384 Pseudoxanthomonas genus 2362:2384 Pseudoxanthomonas genus 2362:2384 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 14 84 contain have 2745:2748 arg2 capacities 2772:2781 interesting metabolic capacities 2750:2781 interesting metabolic capacities 2750:2781 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 14 84 contain have 2745:2748 arg1 Curtobacterium 2682:2695 Curtobacterium 2682:2695 Curtobacterium 2682:2695 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 14 84 contain have 2745:2748 arg1 genera 2725:2730 Bacillus genera 2716:2730 Bacillus genera 2716:2730 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 14 84 contain have 2745:2748 arg1 Streptomyces 2698:2709 Streptomyces 2698:2709 Streptomyces 2698:2709 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 1 85 from Europe 232:237 arg1 typographus 140:150 BACKGROUND Ips typographus 125:150 BACKGROUND Ips typographus (European spruce bark beetle) 125:180 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 1 85 from Europe 232:237 arg1 pest 206:209 the most destructive pest 185:209 the most destructive pest of spruce forests in Europe 185:237 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 11 86 theme I. 1879:1880 arg1 beetle 1894:1899 I. typographus beetle 1879:1899 I. typographus beetle 1879:1899 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 14 87 dep Curtobacterium 2682:2695 arg1 Acinetobacter 2667:2679 Acinetobacter 2667:2679 Acinetobacter 2667:2679 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 1 88 theme destructive 194:204 arg1 typographus 140:150 BACKGROUND Ips typographus 125:150 BACKGROUND Ips typographus (European spruce bark beetle) 125:180 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 1 88 theme destructive 194:204 arg1 pest 206:209 the most destructive pest 185:209 the most destructive pest of spruce forests in Europe 185:237 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 6 89 theme carbon 924:929 arg1 source 931:936 an additional carbon source 910:936 an additional carbon source 910:936 All strains showed the capacity to hydrolyse one or more complex polysaccharides into simpler molecules, which may provide an additional carbon source to its host. 37296446 11 90 theme assimilable 1983:1993 arg1 sources 2002:2008 additional and assimilable carbon sources 1968:2008 additional and assimilable carbon sources for the beetle 1968:2023 CONCLUSION Our results indicate that isolates within the bacteriome of I. typographus beetle have the metabolic potential to increase beetle fitness by proving additional and assimilable carbon sources for the beetle, and by antagonizing fungi entomopathogens. 37296446 14 91 theme metabolic 2762:2770 arg1 capacities 2772:2781 interesting metabolic capacities 2750:2781 interesting metabolic capacities 2750:2781 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 7 92 theme antagonistic 994:1005 arg1 effect 1007:1012 antagonistic effect 994:1012 antagonistic effect 994:1012 Also, 83.9% of the strains isolated showed antagonistic effect against one or more entomopathogenic fungi, which could assist the beetle in its fight against this pathogenic threat. 37296446 7 93 theme strains 970:976 arg1 % 961:961 83.9% 957:961 83.9% of the strains isolated 957:985 Also, 83.9% of the strains isolated showed antagonistic effect against one or more entomopathogenic fungi, which could assist the beetle in its fight against this pathogenic threat. 37296446 7 93 theme strains 970:976 arg1 strains 970:976 the strains 966:976 the strains isolated 966:985 Also, 83.9% of the strains isolated showed antagonistic effect against one or more entomopathogenic fungi, which could assist the beetle in its fight against this pathogenic threat. 37296446 9 94 theme greater 1436:1442 arg1 pupae 1429:1433 pupae 1429:1433 pupae 1429:1433 We have observed an evolution of its bacteriome, which is diverse at the larval phase, substantially diminished in pupae, greater in the teneral adult phase, and similar to that of the larval stage in mature adults. 37296446 14 95 from present 2791:2797 arg1 frequency 2810:2818 a lower frequency 2802:2818 a lower frequency 2802:2818 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 1 96 theme BACKGROUND 125:134 arg1 beetle 174:179 European spruce bark beetle 153:179 European spruce bark beetle 153:179 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 1 96 theme BACKGROUND 125:134 arg1 typographus 140:150 BACKGROUND Ips typographus 125:150 BACKGROUND Ips typographus (European spruce bark beetle) 125:180 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 1 96 theme BACKGROUND 125:134 arg1 pest 206:209 the most destructive pest 185:209 the most destructive pest of spruce forests in Europe 185:237 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 13 97 theme microbiome 2593:2602 arg1 part 2576:2579 part 2576:2579 part of the core microbiome 2576:2602 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 10 98 theme microbiome 1738:1747 arg1 genus 1673:1677 an undescribed genus 1658:1677 an undescribed genus within the Enterobactereaceae family 1658:1714 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 10 98 theme microbiome 1738:1747 arg1 part 1721:1724 part 1721:1724 part of the core microbiome 1721:1747 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 10 98 theme microbiome 1738:1747 arg1 taxa 1555:1558 taxa 1555:1558 taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera 1555:1644 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 8 99 theme bacteriome 1227:1236 arg1 analysis 1211:1218 a taxonomical analysis 1197:1218 a taxonomical analysis of the bacteriome associated with the I. typographus beetle during its different life stages 1197:1311 Using culture-dependent and -independent techniques, we present a taxonomical analysis of the bacteriome associated with the I. typographus beetle during its different life stages. 37296446 9 100 theme adult 1459:1463 arg1 phase 1465:1469 the teneral adult phase 1447:1469 the teneral adult phase 1447:1469 We have observed an evolution of its bacteriome, which is diverse at the larval phase, substantially diminished in pupae, greater in the teneral adult phase, and similar to that of the larval stage in mature adults. 37296446 12 101 contain have 2146:2149 arg2 capacities 2157:2166 these capacities 2151:2166 these capacities 2151:2166 Furthermore, we observed that isolates from adult beetles are more likely to have these capacities but those obtained from larvae showed strongest antifungal activity. 37296446 12 101 contain have 2146:2149 arg1 isolates 2099:2106 isolates 2099:2106 isolates from adult beetles 2099:2125 Furthermore, we observed that isolates from adult beetles are more likely to have these capacities but those obtained from larvae showed strongest antifungal activity. 37296446 12 102 theme antifungal 2216:2225 arg1 activity 2227:2234 strongest antifungal activity 2206:2234 strongest antifungal activity 2206:2234 Furthermore, we observed that isolates from adult beetles are more likely to have these capacities but those obtained from larvae showed strongest antifungal activity. 37296446 14 103 dep group 2644:2648 arg1 addition 2608:2615 addition 2608:2615 addition 2608:2615 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 3 104 from roles 505:509 arg1 ecology 525:531 the beetle ecology 514:531 the beetle ecology 514:531 About the bacteriome, there still are many uncertainties regarding the taxonomical composition, insect-bacteriome interactions, and their potential roles in the beetle ecology. 37296446 5 105 theme different 738:746 arg1 stages 753:758 different life stages 738:758 different life stages of I. typographus beetles 738:784 RESULTS We assessed the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles. 37296446 1 106 theme European 153:160 arg1 beetle 174:179 European spruce bark beetle 153:179 European spruce bark beetle 153:179 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 1 106 theme European 153:160 arg1 typographus 140:150 BACKGROUND Ips typographus 125:150 BACKGROUND Ips typographus (European spruce bark beetle) 125:180 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 13 107 theme Enterobacterales 2442:2457 arg1 group 2459:2463 the Erwiniaceae and Enterobacterales group 2422:2463 the Erwiniaceae and Enterobacterales group 2422:2463 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 8 108 theme different 1291:1299 arg1 stages 1306:1311 its different life stages 1287:1311 its different life stages 1287:1311 Using culture-dependent and -independent techniques, we present a taxonomical analysis of the bacteriome associated with the I. typographus beetle during its different life stages. 37296446 0 109 theme beneficial 101:110 arg1 diversity 79:87 unexplored diversity 68:87 unexplored diversity potentially beneficial to the host 68:122 New insight into the bark beetle ips typographus bacteriome reveals unexplored diversity potentially beneficial to the host. 37296446 13 110 theme new 2400:2402 arg1 taxa 2404:2407 putative new taxa 2391:2407 putative new taxa 2391:2407 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 14 111 theme Bacillus 2716:2723 arg1 genera 2725:2730 Bacillus genera 2716:2730 Bacillus genera 2716:2730 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 5 112 dep RESULTS 652:658 arg1 assessed 663:670 assessed 663:670 assessed the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles 663:784 RESULTS We assessed the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles. 37296446 1 113 theme spruce 214:219 arg1 forests 221:227 spruce forests 214:227 spruce forests in Europe 214:237 BACKGROUND Ips typographus (European spruce bark beetle) is the most destructive pest of spruce forests in Europe. 37296446 2 114 theme beetles 348:354 arg1 biology 332:338 the biology 328:338 the biology of bark beetles 328:354 As for other animals, it has been proposed that the microbiome plays important roles in the biology of bark beetles. 37296446 5 115 theme beetles 778:784 arg1 stages 753:758 different life stages 738:758 different life stages of I. typographus beetles 738:784 RESULTS We assessed the metabolic potential of a collection of isolates obtained from different life stages of I. typographus beetles. 37296446 10 116 dep Pseudoxanthomonas 1605:1621 arg1 the 1601:1603 the 1601:1603 the 1601:1603 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 3 117 theme taxonomical 428:438 arg1 composition 440:450 the taxonomical composition 424:450 the taxonomical composition 424:450 About the bacteriome, there still are many uncertainties regarding the taxonomical composition, insect-bacteriome interactions, and their potential roles in the beetle ecology. 37296446 0 118 theme beetle 26:31 arg1 bacteriome 49:58 the bark beetle ips typographus bacteriome 17:58 the bark beetle ips typographus bacteriome 17:58 New insight into the bark beetle ips typographus bacteriome reveals unexplored diversity potentially beneficial to the host. 37296446 9 119 theme mature 1515:1520 arg1 adults 1522:1527 mature adults 1515:1527 mature adults 1515:1527 We have observed an evolution of its bacteriome, which is diverse at the larval phase, substantially diminished in pupae, greater in the teneral adult phase, and similar to that of the larval stage in mature adults. 37296446 15 120 theme bacteriome 2948:2957 arg1 capacity 2959:2966 the bacteriome capacity to be beneficial to the beetle 2944:2997 the bacteriome capacity to be beneficial to the beetle 2944:2997 Future studies involving bacterial-insect interactions or analysing other potential roles would provide more insights into the bacteriome capacity to be beneficial to the beetle. 37296446 10 121 theme vital 1765:1769 arg1 roles 1771:1775 vital roles 1765:1775 vital roles 1765:1775 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 13 122 theme core 2588:2591 arg1 microbiome 2593:2602 the core microbiome 2584:2602 the core microbiome 2584:2602 Our taxonomical analysis showed that Erwinia typographi, Pseudomonas bohemica, and Pseudomonas typographi species along with Pseudoxanthomonas genus, and putative new taxa belonging to the Erwiniaceae and Enterobacterales group are repeatedly present within the bacteriome of I. typographus beetles, indicating that these species might be part of the core microbiome. 37296446 0 123 theme typographus 37:47 arg1 bacteriome 49:58 the bark beetle ips typographus bacteriome 17:58 the bark beetle ips typographus bacteriome 17:58 New insight into the bark beetle ips typographus bacteriome reveals unexplored diversity potentially beneficial to the host. 37296446 10 124 theme Pseudomonas 1627:1637 arg1 genera 1639:1644 Pseudomonas genera 1627:1644 Pseudomonas genera 1627:1644 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 10 124 theme Pseudomonas 1627:1637 arg1 family 1589:1594 the Erwiniaceae family 1573:1594 the Erwiniaceae family 1573:1594 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 10 125 theme beetle 1792:1797 arg1 fitness 1799:1805 beetle fitness 1792:1805 beetle fitness 1792:1805 Our results suggest that taxa belonging to the Erwiniaceae family, and the Pseudoxanthomonas and Pseudomonas genera, as well as an undescribed genus within the Enterobactereaceae family, are part of the core microbiome and may perform vital roles in maintaining beetle fitness. 37296446 9 126 theme bacteriome 1351:1360 arg1 evolution 1334:1342 an evolution 1331:1342 an evolution of its bacteriome, which is diverse at the larval phase, substantially diminished in pupae, greater in the teneral adult phase, and similar to that of the larval stage in mature adults 1331:1527 We have observed an evolution of its bacteriome, which is diverse at the larval phase, substantially diminished in pupae, greater in the teneral adult phase, and similar to that of the larval stage in mature adults. 37296446 8 127 dep I. 1258:1259 arg1 typographus 1261:1271 typographus 1261:1271 typographus 1261:1271 Using culture-dependent and -independent techniques, we present a taxonomical analysis of the bacteriome associated with the I. typographus beetle during its different life stages. 37296446 14 128 theme Erwinia 2636:2642 arg1 group 2644:2648 Pseudomonas and Erwinia group 2620:2648 Pseudomonas and Erwinia group 2620:2648 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 3 129 theme many 395:398 arg1 uncertainties 400:412 many uncertainties 395:412 many uncertainties regarding the taxonomical composition, insect-bacteriome interactions, and their potential roles in the beetle ecology 395:531 About the bacteriome, there still are many uncertainties regarding the taxonomical composition, insect-bacteriome interactions, and their potential roles in the beetle ecology. 37296446 14 130 attach present 2791:2797 arg1 frequency 2810:2818 a lower frequency 2802:2818 a lower frequency 2802:2818 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 14 130 attach present 2791:2797 arg2 Curtobacterium 2682:2695 Curtobacterium 2682:2695 Curtobacterium 2682:2695 In addition to Pseudomonas and Erwinia group, Staphylococcus, Acinetobacter, Curtobacterium, Streptomyces, and Bacillus genera seem to also have interesting metabolic capacities but are present in a lower frequency. 37296446 3 131 theme potential 495:503 arg1 roles 505:509 their potential roles 489:509 their potential roles in the beetle ecology 489:531 About the bacteriome, there still are many uncertainties regarding the taxonomical composition, insect-bacteriome interactions, and their potential roles in the beetle ecology. 35189234 3 0 theme epilithic 305:313 arg1 biofilms 315:322 epilithic biofilms 305:322 epilithic biofilms 305:322 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 3 0 theme epilithic 305:313 arg1 producers 356:364 the main endogenous primary producers 328:364 the main endogenous primary producers 328:364 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 5 1 theme T-RFLP 758:763 arg1 fingerprints 765:776 T-RFLP fingerprints 758:776 T-RFLP fingerprints of bacteria, archaea and eukaryotes 758:812 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 7 2 theme enhanced 1063:1070 arg1 adsorption 1072:1081 enhanced adsorption 1063:1081 enhanced adsorption 1063:1081 In particular, high levels of CLD were linked with modified exo-polysaccharides corresponding to carbohydrates with enhanced adsorption and adhesion properties. 35189234 4 3 theme bio-assessing 503:515 arg1 pollution 517:525 bio-assessing pollution 503:525 bio-assessing pollution in tropical environments 503:550 Recently, their viscoelastic properties have been shown to be effective in bio-assessing pollution in tropical environments. 35189234 5 4 theme fatty 654:658 arg1 pigments 667:674 pigments 667:674 pigments 667:674 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 5 4 theme fatty 654:658 arg1 acids 660:664 fatty acids 654:664 fatty acids 654:664 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 5 4 theme fatty 654:658 arg1 substances 701:710 extracellular polymeric substances 677:710 extracellular polymeric substances (EPS) 677:716 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 1 5 theme chlordecone 163:173 arg1 contamination 181:193 chlordecone (CLD) contamination 163:193 chlordecone (CLD) contamination 163:193 The rivers of Guadeloupe and Martinique (French West Indies) show high levels of chlordecone (CLD) contamination. 35189234 3 6 theme primary 348:354 arg1 biofilms 315:322 epilithic biofilms 305:322 epilithic biofilms 305:322 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 3 6 theme primary 348:354 arg1 producers 356:364 the main endogenous primary producers 328:364 the main endogenous primary producers 328:364 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 6 7 theme microbial 903:911 arg1 composition 923:933 microbial community composition 903:933 microbial community composition 903:933 Strong links between CLD pollution and both biofilm biochemistry and microbial community composition were found. 35189234 4 8 from effective 490:498 arg1 pollution 517:525 bio-assessing pollution 503:525 bio-assessing pollution in tropical environments 503:550 Recently, their viscoelastic properties have been shown to be effective in bio-assessing pollution in tropical environments. 35189234 5 9 theme biochemical 600:610 arg1 composition 612:622 the biochemical composition 596:622 the biochemical composition of the biofilms 596:638 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 9 10 theme epilithic 1345:1353 arg1 biofilms 1355:1362 epilithic biofilms 1345:1362 epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix 1345:1425 These changes were expected to impact viscoelastic properties of epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix. 35189234 9 11 theme biofilms 1355:1362 arg1 properties 1331:1340 viscoelastic properties 1318:1340 viscoelastic properties of epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix 1318:1425 These changes were expected to impact viscoelastic properties of epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix. 35189234 10 12 theme scavenging 1484:1493 arg1 strategy 1495:1502 a CLD scavenging strategy 1478:1502 a CLD scavenging strategy 1478:1502 They also suggested that microorganisms implement a CLD scavenging strategy, providing new insights on the role of EPS in the adaptation of microorganisms to CLD-polluted environments. 35189234 0 13 theme Chlordecone-contaminated 0:23 arg1 biofilms 35:42 Chlordecone-contaminated epilithic biofilms 0:42 Chlordecone-contaminated epilithic biofilms 0:42 Chlordecone-contaminated epilithic biofilms show increased adsorption capacities. 35189234 4 14 theme viscoelastic 444:455 arg1 properties 457:466 their viscoelastic properties 438:466 their viscoelastic properties 438:466 Recently, their viscoelastic properties have been shown to be effective in bio-assessing pollution in tropical environments. 35189234 3 15 theme main 332:335 arg1 biofilms 315:322 epilithic biofilms 305:322 epilithic biofilms 305:322 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 3 15 theme main 332:335 arg1 producers 356:364 the main endogenous primary producers 328:364 the main endogenous primary producers 328:364 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 7 16 theme high 962:965 arg1 levels 967:972 high levels 962:972 high levels of CLD 962:979 In particular, high levels of CLD were linked with modified exo-polysaccharides corresponding to carbohydrates with enhanced adsorption and adhesion properties. 35189234 2 17 theme human 274:278 arg1 health 280:285 human health 274:285 human health 274:285 This persistent molecule has a dramatic impact on both aquatic ecosystems and human health. 35189234 7 18 with carbohydrates 1044:1056 arg1 adsorption 1072:1081 enhanced adsorption 1063:1081 enhanced adsorption 1063:1081 In particular, high levels of CLD were linked with modified exo-polysaccharides corresponding to carbohydrates with enhanced adsorption and adhesion properties. 35189234 7 18 with carbohydrates 1044:1056 arg1 properties 1096:1105 adhesion properties 1087:1105 adhesion properties 1087:1105 In particular, high levels of CLD were linked with modified exo-polysaccharides corresponding to carbohydrates with enhanced adsorption and adhesion properties. 35189234 3 19 theme endogenous 337:346 arg1 biofilms 315:322 epilithic biofilms 305:322 epilithic biofilms 305:322 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 3 19 theme endogenous 337:346 arg1 producers 356:364 the main endogenous primary producers 328:364 the main endogenous primary producers 328:364 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 6 20 theme biofilm 878:884 arg1 biochemistry 886:897 biofilm biochemistry 878:897 biofilm biochemistry 878:897 Strong links between CLD pollution and both biofilm biochemistry and microbial community composition were found. 35189234 5 21 theme biofilms 631:638 arg1 composition 612:622 the biochemical composition 596:622 the biochemical composition of the biofilms 596:638 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 10 22 theme CLD 1480:1482 arg1 strategy 1495:1502 a CLD scavenging strategy 1478:1502 a CLD scavenging strategy 1478:1502 They also suggested that microorganisms implement a CLD scavenging strategy, providing new insights on the role of EPS in the adaptation of microorganisms to CLD-polluted environments. 35189234 1 23 theme Guadeloupe 96:105 arg1 rivers 86:91 The rivers 82:91 The rivers of Guadeloupe and Martinique (French West Indies) 82:141 The rivers of Guadeloupe and Martinique (French West Indies) show high levels of chlordecone (CLD) contamination. 35189234 2 24 from impact 236:241 arg1 health 280:285 human health 274:285 human health 274:285 This persistent molecule has a dramatic impact on both aquatic ecosystems and human health. 35189234 2 24 from impact 236:241 arg1 ecosystems 259:268 aquatic ecosystems 251:268 aquatic ecosystems 251:268 This persistent molecule has a dramatic impact on both aquatic ecosystems and human health. 35189234 8 25 theme differential 1210:1221 arg1 secretion 1233:1241 a differential microbial secretion 1208:1241 a differential microbial secretion of EPS in response to the pollutant 1208:1277 The observed change probably resulted from a preferential interaction between CLD and sugars and/or a differential microbial secretion of EPS in response to the pollutant. 35189234 0 26 theme epilithic 25:33 arg1 biofilms 35:42 Chlordecone-contaminated epilithic biofilms 0:42 Chlordecone-contaminated epilithic biofilms 0:42 Chlordecone-contaminated epilithic biofilms show increased adsorption capacities. 35189234 8 27 theme microbial 1223:1231 arg1 secretion 1233:1241 a differential microbial secretion 1208:1241 a differential microbial secretion of EPS in response to the pollutant 1208:1277 The observed change probably resulted from a preferential interaction between CLD and sugars and/or a differential microbial secretion of EPS in response to the pollutant. 35189234 3 28 theme central 382:388 arg1 source 395:400 a central food source 380:400 a central food source for fish and crustaceans 380:425 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 8 29 from secretion 1233:1241 arg1 response 1253:1260 response 1253:1260 response to the pollutant 1253:1277 The observed change probably resulted from a preferential interaction between CLD and sugars and/or a differential microbial secretion of EPS in response to the pollutant. 35189234 5 30 theme biochemical 641:651 arg1 markers 749:755 biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers 641:755 biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) 641:813 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 1 31 theme Martinique 111:120 arg1 rivers 86:91 The rivers 82:91 The rivers of Guadeloupe and Martinique (French West Indies) 82:141 The rivers of Guadeloupe and Martinique (French West Indies) show high levels of chlordecone (CLD) contamination. 35189234 1 32 theme contamination 181:193 arg1 levels 153:158 high levels 148:158 high levels of chlordecone (CLD) contamination 148:193 The rivers of Guadeloupe and Martinique (French West Indies) show high levels of chlordecone (CLD) contamination. 35189234 8 33 theme EPS 1246:1248 arg1 secretion 1233:1241 a differential microbial secretion 1208:1241 a differential microbial secretion of EPS in response to the pollutant 1208:1277 The observed change probably resulted from a preferential interaction between CLD and sugars and/or a differential microbial secretion of EPS in response to the pollutant. 35189234 5 34 theme eukaryotes 803:812 arg1 fingerprints 765:776 T-RFLP fingerprints 758:776 T-RFLP fingerprints of bacteria, archaea and eukaryotes 758:812 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 5 35 dep biochemical 641:651 arg1 pigments 667:674 pigments 667:674 pigments 667:674 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 5 35 dep biochemical 641:651 arg1 acids 660:664 fatty acids 654:664 fatty acids 654:664 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 5 35 dep biochemical 641:651 arg1 substances 701:710 extracellular polymeric substances 677:710 extracellular polymeric substances (EPS) 677:716 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 10 36 theme new 1515:1517 arg1 insights 1519:1526 new insights 1515:1526 new insights 1515:1526 They also suggested that microorganisms implement a CLD scavenging strategy, providing new insights on the role of EPS in the adaptation of microorganisms to CLD-polluted environments. 35189234 9 37 theme pollution 1395:1403 arg1 effect 1381:1386 the effect 1377:1386 the effect of CLD pollution on biofilm EPS matrix 1377:1425 These changes were expected to impact viscoelastic properties of epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix. 35189234 10 38 theme EPS 1543:1545 arg1 role 1535:1538 the role 1531:1538 the role of EPS in the adaptation of microorganisms to CLD-polluted environments 1531:1610 They also suggested that microorganisms implement a CLD scavenging strategy, providing new insights on the role of EPS in the adaptation of microorganisms to CLD-polluted environments. 35189234 10 39 theme CLD-polluted 1586:1597 arg1 environments 1599:1610 CLD-polluted environments 1586:1610 CLD-polluted environments 1586:1610 They also suggested that microorganisms implement a CLD scavenging strategy, providing new insights on the role of EPS in the adaptation of microorganisms to CLD-polluted environments. 35189234 0 40 theme adsorption 59:68 arg1 capacities 70:79 increased adsorption capacities 49:79 increased adsorption capacities 49:79 Chlordecone-contaminated epilithic biofilms show increased adsorption capacities. 35189234 5 41 dep markers 749:755 arg1 fingerprints 765:776 T-RFLP fingerprints 758:776 T-RFLP fingerprints of bacteria, archaea and eukaryotes 758:812 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 10 42 theme microorganisms 1568:1581 arg1 adaptation 1554:1563 the adaptation 1550:1563 the adaptation of microorganisms to CLD-polluted environments 1550:1610 They also suggested that microorganisms implement a CLD scavenging strategy, providing new insights on the role of EPS in the adaptation of microorganisms to CLD-polluted environments. 35189234 9 43 theme CLD 1391:1393 arg1 pollution 1395:1403 CLD pollution 1391:1403 CLD pollution 1391:1403 These changes were expected to impact viscoelastic properties of epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix. 35189234 0 44 theme increased 49:57 arg1 capacities 70:79 increased adsorption capacities 49:79 increased adsorption capacities 49:79 Chlordecone-contaminated epilithic biofilms show increased adsorption capacities. 35189234 9 45 theme biofilm 1408:1414 arg1 matrix 1420:1425 biofilm EPS matrix 1408:1425 biofilm EPS matrix 1408:1425 These changes were expected to impact viscoelastic properties of epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix. 35189234 5 46 theme bacteria 781:788 arg1 fingerprints 765:776 T-RFLP fingerprints 758:776 T-RFLP fingerprints of bacteria, archaea and eukaryotes 758:812 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 6 47 theme CLD 855:857 arg1 pollution 859:867 CLD pollution 855:867 CLD pollution 855:867 Strong links between CLD pollution and both biofilm biochemistry and microbial community composition were found. 35189234 2 48 theme dramatic 227:234 arg1 impact 236:241 a dramatic impact 225:241 a dramatic impact on both aquatic ecosystems and human health 225:285 This persistent molecule has a dramatic impact on both aquatic ecosystems and human health. 35189234 5 49 theme molecular 739:747 arg1 markers 749:755 biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers 641:755 biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) 641:813 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 3 50 theme food 390:393 arg1 source 395:400 a central food source 380:400 a central food source for fish and crustaceans 380:425 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 9 51 theme EPS 1416:1418 arg1 matrix 1420:1425 biofilm EPS matrix 1408:1425 biofilm EPS matrix 1408:1425 These changes were expected to impact viscoelastic properties of epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix. 35189234 5 52 theme archaea 791:797 arg1 fingerprints 765:776 T-RFLP fingerprints 758:776 T-RFLP fingerprints of bacteria, archaea and eukaryotes 758:812 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 3 53 from producers 356:364 arg1 rivers 297:302 these rivers 291:302 these rivers 291:302 In these rivers, epilithic biofilms are the main endogenous primary producers and represent a central food source for fish and crustaceans. 35189234 8 54 theme preferential 1153:1164 arg1 interaction 1166:1176 a preferential interaction 1151:1176 a preferential interaction between CLD and sugars 1151:1199 The observed change probably resulted from a preferential interaction between CLD and sugars and/or a differential microbial secretion of EPS in response to the pollutant. 35189234 7 55 theme adhesion 1087:1094 arg1 properties 1096:1105 adhesion properties 1087:1105 adhesion properties 1087:1105 In particular, high levels of CLD were linked with modified exo-polysaccharides corresponding to carbohydrates with enhanced adsorption and adhesion properties. 35189234 4 56 from pollution 517:525 arg1 effective 490:498 effective 490:498 effective 490:498 Recently, their viscoelastic properties have been shown to be effective in bio-assessing pollution in tropical environments. 35189234 4 56 from pollution 517:525 arg1 environments 539:550 tropical environments 530:550 tropical environments 530:550 Recently, their viscoelastic properties have been shown to be effective in bio-assessing pollution in tropical environments. 35189234 8 57 theme observed 1112:1119 arg1 change 1121:1126 The observed change 1108:1126 The observed change probably 1108:1135 The observed change probably resulted from a preferential interaction between CLD and sugars and/or a differential microbial secretion of EPS in response to the pollutant. 35189234 6 58 theme community 913:921 arg1 composition 923:933 microbial community composition 903:933 microbial community composition 903:933 Strong links between CLD pollution and both biofilm biochemistry and microbial community composition were found. 35189234 6 59 theme Strong 834:839 arg1 links 841:845 Strong links 834:845 Strong links between CLD pollution and both biofilm biochemistry and microbial community composition 834:933 Strong links between CLD pollution and both biofilm biochemistry and microbial community composition were found. 35189234 7 60 theme modified 998:1005 arg1 exo-polysaccharides 1007:1025 modified exo-polysaccharides 998:1025 modified exo-polysaccharides corresponding to carbohydrates with enhanced adsorption and adhesion properties 998:1105 In particular, high levels of CLD were linked with modified exo-polysaccharides corresponding to carbohydrates with enhanced adsorption and adhesion properties. 35189234 4 61 theme tropical 530:537 arg1 environments 539:550 tropical environments 530:550 tropical environments 530:550 Recently, their viscoelastic properties have been shown to be effective in bio-assessing pollution in tropical environments. 35189234 5 62 theme extracellular 677:689 arg1 acids 660:664 fatty acids 654:664 fatty acids 654:664 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 5 62 theme extracellular 677:689 arg1 EPS 713:715 EPS 713:715 EPS 713:715 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 5 62 theme extracellular 677:689 arg1 substances 701:710 extracellular polymeric substances 677:710 extracellular polymeric substances (EPS) 677:716 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 2 63 theme persistent 201:210 arg1 molecule 212:219 This persistent molecule 196:219 This persistent molecule 196:219 This persistent molecule has a dramatic impact on both aquatic ecosystems and human health. 35189234 2 64 contain has 221:223 arg2 impact 236:241 a dramatic impact 225:241 a dramatic impact on both aquatic ecosystems and human health 225:285 This persistent molecule has a dramatic impact on both aquatic ecosystems and human health. 35189234 2 64 contain has 221:223 arg1 molecule 212:219 This persistent molecule 196:219 This persistent molecule 196:219 This persistent molecule has a dramatic impact on both aquatic ecosystems and human health. 35189234 5 65 theme polymeric 691:699 arg1 acids 660:664 fatty acids 654:664 fatty acids 654:664 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 5 65 theme polymeric 691:699 arg1 EPS 713:715 EPS 713:715 EPS 713:715 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 5 65 theme polymeric 691:699 arg1 substances 701:710 extracellular polymeric substances 677:710 extracellular polymeric substances (EPS) 677:716 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 35189234 2 66 theme aquatic 251:257 arg1 ecosystems 259:268 aquatic ecosystems 251:268 aquatic ecosystems 251:268 This persistent molecule has a dramatic impact on both aquatic ecosystems and human health. 35189234 9 67 from effect 1381:1386 arg1 matrix 1420:1425 biofilm EPS matrix 1408:1425 biofilm EPS matrix 1408:1425 These changes were expected to impact viscoelastic properties of epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix. 35189234 10 68 from role 1535:1538 arg1 adaptation 1554:1563 the adaptation 1550:1563 the adaptation of microorganisms to CLD-polluted environments 1550:1610 They also suggested that microorganisms implement a CLD scavenging strategy, providing new insights on the role of EPS in the adaptation of microorganisms to CLD-polluted environments. 35189234 1 69 theme high 148:151 arg1 levels 153:158 high levels 148:158 high levels of chlordecone (CLD) contamination 148:193 The rivers of Guadeloupe and Martinique (French West Indies) show high levels of chlordecone (CLD) contamination. 35189234 7 70 attach linked 986:991 arg2 levels 967:972 high levels 962:972 high levels of CLD 962:979 In particular, high levels of CLD were linked with modified exo-polysaccharides corresponding to carbohydrates with enhanced adsorption and adhesion properties. 35189234 7 70 attach linked 986:991 arg3 particular 950:959 particular 950:959 particular 950:959 In particular, high levels of CLD were linked with modified exo-polysaccharides corresponding to carbohydrates with enhanced adsorption and adhesion properties. 35189234 9 71 theme viscoelastic 1318:1329 arg1 properties 1331:1340 viscoelastic properties 1318:1340 viscoelastic properties of epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix 1318:1425 These changes were expected to impact viscoelastic properties of epilithic biofilms highlighting the effect of CLD pollution on biofilm EPS matrix. 35189234 7 72 theme CLD 977:979 arg1 levels 967:972 high levels 962:972 high levels of CLD 962:979 In particular, high levels of CLD were linked with modified exo-polysaccharides corresponding to carbohydrates with enhanced adsorption and adhesion properties. 35189234 5 73 dep acids 660:664 arg1 monosaccharides 718:732 monosaccharides 718:732 monosaccharides 718:732 As these properties are closely related to the biochemical composition of the biofilms, biochemical (fatty acids, pigments, extracellular polymeric substances (EPS) monosaccharides) and molecular markers (T-RFLP fingerprints of bacteria, archaea and eukaryotes) were investigated. 36884369 7 0 dep strains 786:792 arg1 strains 786:792 strains PT2-4T and 62-3T 786:809 strains PT2-4T and 62-3T 786:809 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36884369 7 0 dep strains 786:792 arg1 62-3T 805:809 62-3T 805:809 62-3T 805:809 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36884369 7 0 dep strains 786:792 arg1 PT2-4T 794:799 PT2-4T 794:799 PT2-4T 794:799 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36884369 5 1 dep similarity 583:592 arg1 % 572:572 % 572:572 % 572:572 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 15 2 theme utilization 1714:1724 arg1 loci 1726:1729 polysaccharide utilization loci 1699:1729 polysaccharide utilization loci 1699:1729 Notably, strain PT2-4T can utilize laminarin, fucoidan and alginate via specific carbohydrate-active enzymes encoded in polysaccharide utilization loci, rarely described for the genus Tamlana to date. 36884369 9 3 theme w/v 1082:1084 arg1 NaCl 1087:1090 0-4 % (w/v) NaCl 1075:1090 0-4 % (w/v) NaCl (optimum 0-1 %) 1075:1106 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 9 3 theme w/v 1082:1084 arg1 % 1105:1105 optimum 0-1 % 1093:1105 optimum 0-1 % 1093:1105 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 5 4 theme gene 423:426 arg1 analysis 437:444 16S rRNA gene sequence analysis 414:444 16S rRNA gene sequence analysis 414:444 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 7 5 theme average 724:730 arg1 % 780:780 87.34 and 88.97 % 764:780 87.34 and 88.97 % 764:780 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36884369 7 5 theme average 724:730 arg1 values 752:757 the highest average nucleotide identity values 712:757 the highest average nucleotide identity values 712:757 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36884369 8 6 theme DDH 929:931 arg1 value 933:937 the DDH value 925:937 the DDH value of strain 62-3T 925:953 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 8 6 theme DDH 929:931 arg1 % 964:964 37.7 % 959:964 37.7 % 959:964 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 5 7 dep % 572:572 arg1 97.98 567:571 97.98 567:571 97.98 567:571 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 5 7 dep % 572:572 arg1 98.40 557:561 98.40 557:561 98.40 557:561 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 5 8 theme strains 492:498 arg1 relative 480:487 the closest described relative 458:487 the closest described relative of strains PT2-4T and 62-3T 458:515 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 5 8 theme strains 492:498 arg1 19808T 545:550 Tamlana sedimentorum JCM 19808T 520:550 Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively 520:606 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 3 9 theme validated 256:264 arg1 species 266:272 six validated species 252:272 six validated species 252:272 The genus Tamlana from the Bacteroidota currently includes six validated species. 36884369 4 10 theme China 407:411 arg1 Province 395:402 the Fujian Province 384:402 the Fujian Province of China 384:411 Two strains designated PT2-4T and 62-3T were isolated from Sargassum abundant at the Pingtan island coast in the Fujian Province of China. 36884369 9 11 theme optimum 1093:1099 arg1 NaCl 1087:1090 0-4 % (w/v) NaCl 1075:1090 0-4 % (w/v) NaCl (optimum 0-1 %) 1075:1106 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 9 11 theme optimum 1093:1099 arg1 % 1105:1105 optimum 0-1 % 1093:1105 optimum 0-1 % 1093:1105 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 8 12 theme 62-3T 949:953 arg1 value 933:937 the DDH value 925:937 the DDH value of strain 62-3T 925:953 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 8 12 theme 62-3T 949:953 arg1 % 964:964 37.7 % 959:964 37.7 % 959:964 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 5 13 theme closest 462:468 arg1 relative 480:487 the closest described relative 458:487 the closest described relative of strains PT2-4T and 62-3T 458:515 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 5 13 theme closest 462:468 arg1 19808T 545:550 Tamlana sedimentorum JCM 19808T 520:550 Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively 520:606 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 11 14 dep strains 1207:1213 arg1 strains 1207:1213 strains PT2-4T and 62-3T 1207:1230 strains PT2-4T and 62-3T 1207:1230 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 14 dep strains 1207:1213 arg1 62-3T 1226:1230 62-3T 1226:1230 62-3T 1226:1230 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 14 dep strains 1207:1213 arg1 PT2-4T 1215:1220 PT2-4T 1215:1220 PT2-4T 1215:1220 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 9 15 with 15-40 °C 1044:1051 arg1 NaCl 1087:1090 0-4 % (w/v) NaCl 1075:1090 0-4 % (w/v) NaCl (optimum 0-1 %) 1075:1106 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 9 15 with 15-40 °C 1044:1051 arg1 % 1105:1105 optimum 0-1 % 1093:1105 optimum 0-1 % 1093:1105 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 10 16 dep optimum 1164:1170 arg1 pH 1173:1174 pH 7.0 1173:1178 pH 7.0 1173:1178 Strains PT2-4T and 62-3T can grow from pH 5.0 to 10.0 (optimum, pH 7.0). 36884369 18 17 theme 1K04427T=KCTC 2067:2079 arg1 92183T 2081:2086 type strain PT2-4T=MCCC 1K04427T=KCTC 92183T 2043:2086 type strain PT2-4T=MCCC 1K04427T=KCTC 92183T 2043:2086 nov. (type strain PT2-4T=MCCC 1K04427T=KCTC 92183T and type strain 62-3T=MCCC 1K04421T=KCTC 92182T). 36884369 11 18 theme fatty 1192:1196 arg1 iso-C15  1236:1243 iso-C15  1236:1243 iso-C15  1236:1243 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 18 theme fatty 1192:1196 arg1 acids 1198:1202 The major fatty acids 1182:1202 The major fatty acids of strains PT2-4T and 62-3T 1182:1230 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 18 theme fatty 1192:1196 arg1 iso 1252:1254 iso 1252:1254 iso 1252:1254 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 18 theme fatty 1192:1196 arg1  1 1263:1264  1 1263:1264  1 1263:1264 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 18 theme fatty 1192:1196 arg1  0 1245:1246  0 1245:1246  0 1245:1246 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 2 19 theme novel 73:77 arg1 nov. 63:66 nov. 63:66 nov. 63:66 nov., two novel species isolated from Sargassum, show genomic and physiological adaptations for a Sargassum-associated lifestyle. 36884369 2 19 theme novel 73:77 arg1 species 79:85 two novel species 69:85 two novel species isolated from Sargassum 69:109 nov., two novel species isolated from Sargassum, show genomic and physiological adaptations for a Sargassum-associated lifestyle. 36884369 13 20 theme corresponding 1375:1387 arg1 features 1398:1405 corresponding adaptive features 1375:1405 corresponding adaptive features 1375:1405 Genomic and physiological analyses of strains PT2-4T and 62-3T showed corresponding adaptive features. 36884369 18 21 theme strain 2048:2053 arg1 92183T 2081:2086 type strain PT2-4T=MCCC 1K04427T=KCTC 92183T 2043:2086 type strain PT2-4T=MCCC 1K04427T=KCTC 92183T 2043:2086 nov. (type strain PT2-4T=MCCC 1K04427T=KCTC 92183T and type strain 62-3T=MCCC 1K04421T=KCTC 92182T). 36884369 1 22 dep sp 59:60 arg1 sargassicola 46:57 nov. and Tamlana sargassicola 29:57 nov. and Tamlana sargassicola 29:57 nov. and Tamlana sargassicola sp. 36884369 6 23 theme strain 655:660 arg1 PT2-4T 662:667 strain PT2-4T 655:667 strain PT2-4T 655:667 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T was 98.68 %. 36884369 16 24 dep strains 1894:1900 arg1 strains 1894:1900 strains 1894:1900 strains PT2-4T and 62-3T 1894:1917 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 16 24 dep strains 1894:1900 arg1 62-3T 1913:1917 62-3T 1913:1917 62-3T 1913:1917 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 16 24 dep strains 1894:1900 arg1 PT2-4T 1902:1907 PT2-4T 1902:1907 PT2-4T 1902:1907 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 14 25 theme diverse 1519:1525 arg1 polysaccharides 1527:1541 brown algae-derived diverse polysaccharides 1499:1541 brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan) 1499:1576 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 25 theme diverse 1519:1525 arg1 fucoidan 1568:1575 fucoidan 1568:1575 fucoidan 1568:1575 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 25 theme diverse 1519:1525 arg1 laminarin 1554:1562 laminarin 1554:1562 laminarin 1554:1562 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 25 theme diverse 1519:1525 arg1 alginate 1544:1551 alginate 1544:1551 alginate 1544:1551 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 17 26 dep sp 2033:2034 arg1 sargassicola 2020:2031 nov. and Tamlana sargassicola 2003:2031 nov. and Tamlana sargassicola 2003:2031 nov. and Tamlana sargassicola sp. 36884369 15 27 theme strain 1588:1593 arg1 PT2-4T 1595:1600 strain PT2-4T 1588:1600 strain PT2-4T 1588:1600 Notably, strain PT2-4T can utilize laminarin, fucoidan and alginate via specific carbohydrate-active enzymes encoded in polysaccharide utilization loci, rarely described for the genus Tamlana to date. 36884369 14 28 theme brown 1499:1503 arg1 polysaccharides 1527:1541 brown algae-derived diverse polysaccharides 1499:1541 brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan) 1499:1576 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 28 theme brown 1499:1503 arg1 fucoidan 1568:1575 fucoidan 1568:1575 fucoidan 1568:1575 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 28 theme brown 1499:1503 arg1 laminarin 1554:1562 laminarin 1554:1562 laminarin 1554:1562 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 28 theme brown 1499:1503 arg1 alginate 1544:1551 alginate 1544:1551 alginate 1544:1551 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 5 29 theme sedimentorum 528:539 arg1 relative 480:487 the closest described relative 458:487 the closest described relative of strains PT2-4T and 62-3T 458:515 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 5 29 theme sedimentorum 528:539 arg1 19808T 545:550 Tamlana sedimentorum JCM 19808T 520:550 Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively 520:606 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 8 30 theme highest 830:836 arg1 value 866:870 The highest DNA-DNA hybridization (DDH) value 826:870 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T 826:887 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 8 30 theme highest 830:836 arg1 % 898:898 35.2 % 893:898 35.2 % 893:898 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 6 31 theme gene 622:625 arg1 % 696:696 98.68 % 690:696 98.68 % 690:696 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T was 98.68 %. 36884369 6 31 theme gene 622:625 arg1 similarity 636:645 The 16S rRNA gene sequence similarity 609:645 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T 609:684 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T was 98.68 %. 36884369 8 32 theme hybridization 846:858 arg1 value 866:870 The highest DNA-DNA hybridization (DDH) value 826:870 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T 826:887 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 8 32 theme hybridization 846:858 arg1 % 898:898 35.2 % 893:898 35.2 % 893:898 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 4 33 attach isolated 320:327 arg1 Sargassum 334:342 Sargassum 334:342 Sargassum abundant at the Pingtan island coast in the Fujian Province of China 334:411 Two strains designated PT2-4T and 62-3T were isolated from Sargassum abundant at the Pingtan island coast in the Fujian Province of China. 36884369 4 33 attach isolated 320:327 arg2 strains 279:285 Two strains 275:285 Two strains designated PT2-4T and 62-3T 275:313 Two strains designated PT2-4T and 62-3T were isolated from Sargassum abundant at the Pingtan island coast in the Fujian Province of China. 36884369 16 34 theme novel 1959:1963 arg1 sp 1999:2000 Tamlana laminarinivorans sp 1974:2000 Tamlana laminarinivorans sp 1974:2000 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 16 34 theme novel 1959:1963 arg1 species 1965:1971 two novel species 1955:1971 two novel species 1955:1971 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 6 35 theme 16S 613:615 arg1 % 696:696 98.68 % 690:696 98.68 % 690:696 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T was 98.68 %. 36884369 6 35 theme 16S 613:615 arg1 similarity 636:645 The 16S rRNA gene sequence similarity 609:645 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T 609:684 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T was 98.68 %. 36884369 8 36 theme sedimentorum 974:985 arg1 19808T 991:996 T. sedimentorum JCM 19808T 971:996 T. sedimentorum JCM 19808T 971:996 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 15 37 theme specific 1651:1658 arg1 enzymes 1680:1686 specific carbohydrate-active enzymes 1651:1686 specific carbohydrate-active enzymes encoded in polysaccharide utilization loci, rarely described for the genus Tamlana to date 1651:1777 Notably, strain PT2-4T can utilize laminarin, fucoidan and alginate via specific carbohydrate-active enzymes encoded in polysaccharide utilization loci, rarely described for the genus Tamlana to date. 36884369 10 38 dep Strains 1109:1115 arg1 PT2-4T 1117:1122 PT2-4T 1117:1122 PT2-4T 1117:1122 Strains PT2-4T and 62-3T can grow from pH 5.0 to 10.0 (optimum, pH 7.0). 36884369 10 38 dep Strains 1109:1115 arg1 Strains 1109:1115 Strains PT2-4T and 62-3T 1109:1132 Strains PT2-4T and 62-3T 1109:1132 Strains PT2-4T and 62-3T can grow from pH 5.0 to 10.0 (optimum, pH 7.0). 36884369 10 38 dep Strains 1109:1115 arg1 62-3T 1128:1132 62-3T 1128:1132 62-3T 1128:1132 Strains PT2-4T and 62-3T can grow from pH 5.0 to 10.0 (optimum, pH 7.0). 36884369 9 39 dep optimum 1054:1060 arg1 30 °C 1063:1067 30 °C 1063:1067 30 °C 1063:1067 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 16 40 theme laminarinivorans 1982:1997 arg1 sp 1999:2000 Tamlana laminarinivorans sp 1974:2000 Tamlana laminarinivorans sp 1974:2000 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 16 40 theme laminarinivorans 1982:1997 arg1 species 1965:1971 two novel species 1955:1971 two novel species 1955:1971 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 18 41 dep nov 2037:2039 arg1 92182T 2129:2134 type strain 62-3T=MCCC 1K04421T=KCTC 92182T 2092:2134 type strain 62-3T=MCCC 1K04421T=KCTC 92182T 2092:2134 nov. (type strain PT2-4T=MCCC 1K04427T=KCTC 92183T and type strain 62-3T=MCCC 1K04421T=KCTC 92182T). 36884369 18 41 dep nov 2037:2039 arg1 92183T 2081:2086 type strain PT2-4T=MCCC 1K04427T=KCTC 92183T 2043:2086 type strain PT2-4T=MCCC 1K04427T=KCTC 92183T 2043:2086 nov. (type strain PT2-4T=MCCC 1K04427T=KCTC 92183T and type strain 62-3T=MCCC 1K04421T=KCTC 92182T). 36884369 5 42 theme sequence 574:581 arg1 similarity 583:592 98.40 and 97.98% sequence similarity 557:592 98.40 and 97.98% sequence similarity 557:592 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 16 43 theme polysaccharides 1862:1876 arg1 characteristics 1818:1832 their distinct physiological characteristics 1789:1832 their distinct physiological characteristics 1789:1832 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 16 43 theme polysaccharides 1862:1876 arg1 traits 1842:1847 the traits 1838:1847 the traits of utilizing polysaccharides from Sargassum 1838:1891 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 8 44 theme strain 875:880 arg1 PT2-4T 882:887 strain PT2-4T 875:887 strain PT2-4T 875:887 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 8 45 with % 898:898 arg1 62-3T 912:916 strain 62-3T 905:916 strain 62-3T 905:916 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 16 46 from characteristics 1818:1832 arg1 Sargassum 1883:1891 Sargassum 1883:1891 Sargassum 1883:1891 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 5 47 theme Tamlana 520:526 arg1 relative 480:487 the closest described relative 458:487 the closest described relative of strains PT2-4T and 62-3T 458:515 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 5 47 theme Tamlana 520:526 arg1 19808T 545:550 Tamlana sedimentorum JCM 19808T 520:550 Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively 520:606 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 2 48 theme Sargassum-associated 161:180 arg1 lifestyle 182:190 a Sargassum-associated lifestyle 159:190 a Sargassum-associated lifestyle 159:190 nov., two novel species isolated from Sargassum, show genomic and physiological adaptations for a Sargassum-associated lifestyle. 36884369 14 49 dep polysaccharides 1527:1541 arg1 polysaccharides 1527:1541 brown algae-derived diverse polysaccharides 1499:1541 brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan) 1499:1576 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 49 dep polysaccharides 1527:1541 arg1 fucoidan 1568:1575 fucoidan 1568:1575 fucoidan 1568:1575 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 49 dep polysaccharides 1527:1541 arg1 laminarin 1554:1562 laminarin 1554:1562 laminarin 1554:1562 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 49 dep polysaccharides 1527:1541 arg1 alginate 1544:1551 alginate 1544:1551 alginate 1544:1551 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 17 50 theme nov. 2003:2006 arg1 sargassicola 2020:2031 nov. and Tamlana sargassicola 2003:2031 nov. and Tamlana sargassicola 2003:2031 nov. and Tamlana sargassicola sp. 36884369 3 51 from Bacteroidota 220:231 arg1 Tamlana 203:209 The genus Tamlana 193:209 The genus Tamlana from the Bacteroidota 193:231 The genus Tamlana from the Bacteroidota currently includes six validated species. 36884369 12 52 theme sole 1279:1282 arg1 quinone 1296:1302 the sole respiratory quinone 1275:1302 the sole respiratory quinone 1275:1302 MK-6 is the sole respiratory quinone. 36884369 12 52 theme sole 1279:1282 arg1 MK-6 1267:1270 MK-6 1267:1270 MK-6 1267:1270 MK-6 is the sole respiratory quinone. 36884369 9 53 dep strains 1009:1015 arg1 strains 1009:1015 strains PT2-4T and 62-3T 1009:1032 strains PT2-4T and 62-3T 1009:1032 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 9 53 dep strains 1009:1015 arg1 62-3T 1028:1032 62-3T 1028:1032 62-3T 1028:1032 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 9 53 dep strains 1009:1015 arg1 PT2-4T 1017:1022 PT2-4T 1017:1022 PT2-4T 1017:1022 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 18 54 theme strain 2097:2102 arg1 92182T 2129:2134 type strain 62-3T=MCCC 1K04421T=KCTC 92182T 2092:2134 type strain 62-3T=MCCC 1K04421T=KCTC 92182T 2092:2134 nov. (type strain PT2-4T=MCCC 1K04427T=KCTC 92183T and type strain 62-3T=MCCC 1K04421T=KCTC 92182T). 36884369 17 55 theme Tamlana 2012:2018 arg1 sargassicola 2020:2031 nov. and Tamlana sargassicola 2003:2031 nov. and Tamlana sargassicola 2003:2031 nov. and Tamlana sargassicola sp. 36884369 15 56 theme polysaccharide 1699:1712 arg1 loci 1726:1729 polysaccharide utilization loci 1699:1729 polysaccharide utilization loci 1699:1729 Notably, strain PT2-4T can utilize laminarin, fucoidan and alginate via specific carbohydrate-active enzymes encoded in polysaccharide utilization loci, rarely described for the genus Tamlana to date. 36884369 16 57 theme distinct 1795:1802 arg1 characteristics 1818:1832 their distinct physiological characteristics 1789:1832 their distinct physiological characteristics 1789:1832 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 9 58 theme 0-4  1075:1078 arg1 NaCl 1087:1090 0-4 % (w/v) NaCl 1075:1090 0-4 % (w/v) NaCl (optimum 0-1 %) 1075:1106 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 9 58 theme 0-4  1075:1078 arg1 % 1105:1105 optimum 0-1 % 1093:1105 optimum 0-1 % 1093:1105 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 7 59 theme nucleotide 732:741 arg1 % 780:780 87.34 and 88.97 % 764:780 87.34 and 88.97 % 764:780 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36884369 7 59 theme nucleotide 732:741 arg1 values 752:757 the highest average nucleotide identity values 712:757 the highest average nucleotide identity values 712:757 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36884369 4 60 theme abundant 344:351 arg1 Sargassum 334:342 Sargassum 334:342 Sargassum abundant at the Pingtan island coast in the Fujian Province of China 334:411 Two strains designated PT2-4T and 62-3T were isolated from Sargassum abundant at the Pingtan island coast in the Fujian Province of China. 36884369 11 61 theme strains 1207:1213 arg1 iso-C15  1236:1243 iso-C15  1236:1243 iso-C15  1236:1243 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 61 theme strains 1207:1213 arg1 acids 1198:1202 The major fatty acids 1182:1202 The major fatty acids of strains PT2-4T and 62-3T 1182:1230 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 61 theme strains 1207:1213 arg1 iso 1252:1254 iso 1252:1254 iso 1252:1254 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 61 theme strains 1207:1213 arg1  1 1263:1264  1 1263:1264  1 1263:1264 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 61 theme strains 1207:1213 arg1  0 1245:1246  0 1245:1246  0 1245:1246 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 5 62 theme rRNA 418:421 arg1 analysis 437:444 16S rRNA gene sequence analysis 414:444 16S rRNA gene sequence analysis 414:444 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 7 63 theme highest 716:722 arg1 % 780:780 87.34 and 88.97 % 764:780 87.34 and 88.97 % 764:780 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36884369 7 63 theme highest 716:722 arg1 values 752:757 the highest average nucleotide identity values 712:757 the highest average nucleotide identity values 712:757 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36884369 18 64 theme 1K04421T=KCTC 2115:2127 arg1 92182T 2129:2134 type strain 62-3T=MCCC 1K04421T=KCTC 92182T 2092:2134 type strain 62-3T=MCCC 1K04421T=KCTC 92182T 2092:2134 nov. (type strain PT2-4T=MCCC 1K04427T=KCTC 92183T and type strain 62-3T=MCCC 1K04421T=KCTC 92182T). 36884369 5 65 theme sequence 428:435 arg1 analysis 437:444 16S rRNA gene sequence analysis 414:444 16S rRNA gene sequence analysis 414:444 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 8 66 theme strain 942:947 arg1 62-3T 949:953 strain 62-3T 942:953 strain 62-3T 942:953 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 2 67 attach isolated 87:94 arg2 species 79:85 two novel species 69:85 two novel species isolated from Sargassum 69:109 nov., two novel species isolated from Sargassum, show genomic and physiological adaptations for a Sargassum-associated lifestyle. 36884369 2 67 attach isolated 87:94 arg1 Sargassum 101:109 Sargassum 101:109 Sargassum 101:109 nov., two novel species isolated from Sargassum, show genomic and physiological adaptations for a Sargassum-associated lifestyle. 36884369 2 67 attach isolated 87:94 arg2 nov. 63:66 nov. 63:66 nov. 63:66 nov., two novel species isolated from Sargassum, show genomic and physiological adaptations for a Sargassum-associated lifestyle. 36884369 15 68 theme carbohydrate-active 1660:1678 arg1 enzymes 1680:1686 specific carbohydrate-active enzymes 1651:1686 specific carbohydrate-active enzymes encoded in polysaccharide utilization loci, rarely described for the genus Tamlana to date 1651:1777 Notably, strain PT2-4T can utilize laminarin, fucoidan and alginate via specific carbohydrate-active enzymes encoded in polysaccharide utilization loci, rarely described for the genus Tamlana to date. 36884369 2 69 theme physiological 129:141 arg1 adaptations 143:153 genomic and physiological adaptations 117:153 genomic and physiological adaptations 117:153 nov., two novel species isolated from Sargassum, show genomic and physiological adaptations for a Sargassum-associated lifestyle. 36884369 16 70 from Sargassum 1883:1891 arg1 characteristics 1818:1832 their distinct physiological characteristics 1789:1832 their distinct physiological characteristics 1789:1832 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 16 70 from Sargassum 1883:1891 arg1 traits 1842:1847 the traits 1838:1847 the traits of utilizing polysaccharides from Sargassum 1838:1891 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 16 70 from Sargassum 1883:1891 arg1 polysaccharides 1862:1876 utilizing polysaccharides 1852:1876 utilizing polysaccharides from Sargassum 1852:1891 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 2 71 theme genomic 117:123 arg1 adaptations 143:153 genomic and physiological adaptations 117:153 genomic and physiological adaptations 117:153 nov., two novel species isolated from Sargassum, show genomic and physiological adaptations for a Sargassum-associated lifestyle. 36884369 9 72 theme 0-1  1101:1104 arg1 NaCl 1087:1090 0-4 % (w/v) NaCl 1075:1090 0-4 % (w/v) NaCl (optimum 0-1 %) 1075:1106 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 9 72 theme 0-1  1101:1104 arg1 % 1105:1105 optimum 0-1 % 1093:1105 optimum 0-1 % 1093:1105 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 13 73 theme adaptive 1389:1396 arg1 features 1398:1405 corresponding adaptive features 1375:1405 corresponding adaptive features 1375:1405 Genomic and physiological analyses of strains PT2-4T and 62-3T showed corresponding adaptive features. 36884369 18 74 theme type 2043:2046 arg1 92183T 2081:2086 type strain PT2-4T=MCCC 1K04427T=KCTC 92183T 2043:2086 type strain PT2-4T=MCCC 1K04427T=KCTC 92183T 2043:2086 nov. (type strain PT2-4T=MCCC 1K04427T=KCTC 92183T and type strain 62-3T=MCCC 1K04421T=KCTC 92182T). 36884369 4 75 theme Fujian 388:393 arg1 Province 395:402 the Fujian Province 384:402 the Fujian Province of China 384:411 Two strains designated PT2-4T and 62-3T were isolated from Sargassum abundant at the Pingtan island coast in the Fujian Province of China. 36884369 15 76 theme genus 1757:1761 arg1 Tamlana 1763:1769 the genus Tamlana 1753:1769 the genus Tamlana to date 1753:1777 Notably, strain PT2-4T can utilize laminarin, fucoidan and alginate via specific carbohydrate-active enzymes encoded in polysaccharide utilization loci, rarely described for the genus Tamlana to date. 36884369 5 77 theme described 470:478 arg1 relative 480:487 the closest described relative 458:487 the closest described relative of strains PT2-4T and 62-3T 458:515 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 5 77 theme described 470:478 arg1 19808T 545:550 Tamlana sedimentorum JCM 19808T 520:550 Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively 520:606 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 4 78 theme island 368:373 arg1 coast 375:379 the Pingtan island coast 356:379 the Pingtan island coast in the Fujian Province of China 356:411 Two strains designated PT2-4T and 62-3T were isolated from Sargassum abundant at the Pingtan island coast in the Fujian Province of China. 36884369 4 79 from coast 375:379 arg1 abundant 344:351 abundant 344:351 abundant 344:351 Two strains designated PT2-4T and 62-3T were isolated from Sargassum abundant at the Pingtan island coast in the Fujian Province of China. 36884369 4 79 from coast 375:379 arg1 Province 395:402 the Fujian Province 384:402 the Fujian Province of China 384:411 Two strains designated PT2-4T and 62-3T were isolated from Sargassum abundant at the Pingtan island coast in the Fujian Province of China. 36884369 14 80 theme growth 1438:1443 arg1 environment 1445:1455 the growth environment 1434:1455 the growth environment of macroalgae 1434:1469 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 11 81 theme major 1186:1190 arg1 iso-C15  1236:1243 iso-C15  1236:1243 iso-C15  1236:1243 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 81 theme major 1186:1190 arg1 acids 1198:1202 The major fatty acids 1182:1202 The major fatty acids of strains PT2-4T and 62-3T 1182:1230 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 81 theme major 1186:1190 arg1 iso 1252:1254 iso 1252:1254 iso 1252:1254 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 81 theme major 1186:1190 arg1  1 1263:1264  1 1263:1264  1 1263:1264 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 81 theme major 1186:1190 arg1  0 1245:1246  0 1245:1246  0 1245:1246 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 8 82 with % 964:964 arg1 19808T 991:996 T. sedimentorum JCM 19808T 971:996 T. sedimentorum JCM 19808T 971:996 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 18 83 theme PT2-4T=MCCC 2055:2065 arg1 92183T 2081:2086 type strain PT2-4T=MCCC 1K04427T=KCTC 92183T 2043:2086 type strain PT2-4T=MCCC 1K04427T=KCTC 92183T 2043:2086 nov. (type strain PT2-4T=MCCC 1K04427T=KCTC 92183T and type strain 62-3T=MCCC 1K04421T=KCTC 92182T). 36884369 11 84 dep iso-C15  1236:1243 arg1 iso-C15  1236:1243 iso-C15  1236:1243 iso-C15  1236:1243 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 84 dep iso-C15  1236:1243 arg1 acids 1198:1202 The major fatty acids 1182:1202 The major fatty acids of strains PT2-4T and 62-3T 1182:1230 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 84 dep iso-C15  1236:1243 arg1 iso 1252:1254 iso 1252:1254 iso 1252:1254 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 84 dep iso-C15  1236:1243 arg1  1 1263:1264  1 1263:1264  1 1263:1264 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 11 84 dep iso-C15  1236:1243 arg1  0 1245:1246  0 1245:1246  0 1245:1246 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 16 85 dep distinct 1795:1802 arg1 physiological 1804:1816 physiological 1804:1816 physiological 1804:1816 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 5 86 dep strains 492:498 arg1 PT2-4T 500:505 PT2-4T 500:505 PT2-4T 500:505 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 5 86 dep strains 492:498 arg1 strains 492:498 strains PT2-4T and 62-3T 492:515 strains PT2-4T and 62-3T 492:515 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 5 86 dep strains 492:498 arg1 62-3T 511:515 62-3T 511:515 62-3T 511:515 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 14 87 theme polysaccharides 1527:1541 arg1 degradation 1484:1494 the degradation 1480:1494 the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan) 1480:1576 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 11 88 dep  0 1245:1246 arg1 G-C15  1256:1261 G-C15  1256:1261 G-C15  1256:1261 The major fatty acids of strains PT2-4T and 62-3T are iso-C15 : 0 and iso G-C15 : 1. 36884369 14 89 theme Significant 1408:1418 arg1 adaptation 1420:1429 Significant adaptation 1408:1429 Significant adaptation to the growth environment of macroalgae 1408:1469 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 16 90 from traits 1842:1847 arg1 Sargassum 1883:1891 Sargassum 1883:1891 Sargassum 1883:1891 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 14 91 theme algae-derived 1505:1517 arg1 polysaccharides 1527:1541 brown algae-derived diverse polysaccharides 1499:1541 brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan) 1499:1576 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 91 theme algae-derived 1505:1517 arg1 fucoidan 1568:1575 fucoidan 1568:1575 fucoidan 1568:1575 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 91 theme algae-derived 1505:1517 arg1 laminarin 1554:1562 laminarin 1554:1562 laminarin 1554:1562 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 91 theme algae-derived 1505:1517 arg1 alginate 1544:1551 alginate 1544:1551 alginate 1544:1551 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 13 92 theme strains 1343:1349 arg1 analyses 1331:1338 Genomic and physiological analyses 1305:1338 Genomic and physiological analyses of strains PT2-4T and 62-3T 1305:1366 Genomic and physiological analyses of strains PT2-4T and 62-3T showed corresponding adaptive features. 36884369 10 93 dep pH 1148:1149 arg1 to 1155:1156 to 1155:1156 to 1155:1156 Strains PT2-4T and 62-3T can grow from pH 5.0 to 10.0 (optimum, pH 7.0). 36884369 6 94 theme sequence 627:634 arg1 % 696:696 98.68 % 690:696 98.68 % 690:696 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T was 98.68 %. 36884369 6 94 theme sequence 627:634 arg1 similarity 636:645 The 16S rRNA gene sequence similarity 609:645 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T 609:684 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T was 98.68 %. 36884369 8 95 theme T. 971:972 arg1 19808T 991:996 T. sedimentorum JCM 19808T 971:996 T. sedimentorum JCM 19808T 971:996 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 5 96 theme JCM 541:543 arg1 relative 480:487 the closest described relative 458:487 the closest described relative of strains PT2-4T and 62-3T 458:515 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 5 96 theme JCM 541:543 arg1 19808T 545:550 Tamlana sedimentorum JCM 19808T 520:550 Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively 520:606 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 6 97 theme rRNA 617:620 arg1 % 696:696 98.68 % 690:696 98.68 % 690:696 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T was 98.68 %. 36884369 6 97 theme rRNA 617:620 arg1 similarity 636:645 The 16S rRNA gene sequence similarity 609:645 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T 609:684 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T was 98.68 %. 36884369 8 98 theme JCM 987:989 arg1 19808T 991:996 T. sedimentorum JCM 19808T 971:996 T. sedimentorum JCM 19808T 971:996 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 8 99 theme DNA-DNA 838:844 arg1 DDH 861:863 DDH 861:863 DDH 861:863 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 8 99 theme DNA-DNA 838:844 arg1 hybridization 846:858 DNA-DNA hybridization 838:858 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T 826:887 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 5 100 with 19808T 545:550 arg1 similarity 583:592 98.40 and 97.98% sequence similarity 557:592 98.40 and 97.98% sequence similarity 557:592 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 9 101 theme strains 1009:1015 arg1 Growth 999:1004 Growth 999:1004 Growth of strains PT2-4T and 62-3T 999:1032 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 14 102 theme macroalgae 1460:1469 arg1 environment 1445:1455 the growth environment 1434:1455 the growth environment of macroalgae 1434:1469 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 16 103 theme utilizing 1852:1860 arg1 polysaccharides 1862:1876 utilizing polysaccharides 1852:1876 utilizing polysaccharides from Sargassum 1852:1891 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 3 104 theme genus 197:201 arg1 Tamlana 203:209 The genus Tamlana 193:209 The genus Tamlana from the Bacteroidota 193:231 The genus Tamlana from the Bacteroidota currently includes six validated species. 36884369 13 105 theme Genomic 1305:1311 arg1 analyses 1331:1338 Genomic and physiological analyses 1305:1338 Genomic and physiological analyses of strains PT2-4T and 62-3T 1305:1366 Genomic and physiological analyses of strains PT2-4T and 62-3T showed corresponding adaptive features. 36884369 16 106 theme Tamlana 1974:1980 arg1 sp 1999:2000 Tamlana laminarinivorans sp 1974:2000 Tamlana laminarinivorans sp 1974:2000 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 16 106 theme Tamlana 1974:1980 arg1 species 1965:1971 two novel species 1955:1971 two novel species 1955:1971 Based on their distinct physiological characteristics and the traits of utilizing polysaccharides from Sargassum, strains PT2-4T and 62-3T are suggested to be classified into two novel species, Tamlana laminarinivorans sp. 36884369 13 107 theme physiological 1317:1329 arg1 analyses 1331:1338 Genomic and physiological analyses 1305:1338 Genomic and physiological analyses of strains PT2-4T and 62-3T 1305:1366 Genomic and physiological analyses of strains PT2-4T and 62-3T showed corresponding adaptive features. 36884369 13 108 dep strains 1343:1349 arg1 strains 1343:1349 strains PT2-4T and 62-3T 1343:1366 strains PT2-4T and 62-3T 1343:1366 Genomic and physiological analyses of strains PT2-4T and 62-3T showed corresponding adaptive features. 36884369 13 108 dep strains 1343:1349 arg1 62-3T 1362:1366 62-3T 1362:1366 62-3T 1362:1366 Genomic and physiological analyses of strains PT2-4T and 62-3T showed corresponding adaptive features. 36884369 13 108 dep strains 1343:1349 arg1 PT2-4T 1351:1356 PT2-4T 1351:1356 PT2-4T 1351:1356 Genomic and physiological analyses of strains PT2-4T and 62-3T showed corresponding adaptive features. 36884369 6 109 theme strain 673:678 arg1 62-3T 680:684 strain 62-3T 673:684 strain 62-3T 673:684 The 16S rRNA gene sequence similarity between strain PT2-4T and strain 62-3T was 98.68 %. 36884369 8 110 theme PT2-4T 882:887 arg1 value 866:870 The highest DNA-DNA hybridization (DDH) value 826:870 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T 826:887 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 8 110 theme PT2-4T 882:887 arg1 % 898:898 35.2 % 893:898 35.2 % 893:898 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 18 111 theme 62-3T=MCCC 2104:2113 arg1 92182T 2129:2134 type strain 62-3T=MCCC 1K04421T=KCTC 92182T 2092:2134 type strain 62-3T=MCCC 1K04421T=KCTC 92182T 2092:2134 nov. (type strain PT2-4T=MCCC 1K04427T=KCTC 92183T and type strain 62-3T=MCCC 1K04421T=KCTC 92182T). 36884369 1 112 theme nov. 29:32 arg1 sargassicola 46:57 nov. and Tamlana sargassicola 29:57 nov. and Tamlana sargassicola 29:57 nov. and Tamlana sargassicola sp. 36884369 4 113 theme Pingtan 360:366 arg1 island 368:373 the Pingtan island 356:373 the Pingtan island coast in the Fujian Province of China 356:411 Two strains designated PT2-4T and 62-3T were isolated from Sargassum abundant at the Pingtan island coast in the Fujian Province of China. 36884369 18 114 theme type 2092:2095 arg1 92182T 2129:2134 type strain 62-3T=MCCC 1K04421T=KCTC 92182T 2092:2134 type strain 62-3T=MCCC 1K04421T=KCTC 92182T 2092:2134 nov. (type strain PT2-4T=MCCC 1K04427T=KCTC 92183T and type strain 62-3T=MCCC 1K04421T=KCTC 92182T). 36884369 14 115 link algae-derived 1505:1517 arg1 polysaccharides 1527:1541 brown algae-derived diverse polysaccharides 1499:1541 brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan) 1499:1576 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 115 link algae-derived 1505:1517 arg1 fucoidan 1568:1575 fucoidan 1568:1575 fucoidan 1568:1575 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 115 link algae-derived 1505:1517 arg1 laminarin 1554:1562 laminarin 1554:1562 laminarin 1554:1562 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 14 115 link algae-derived 1505:1517 arg1 alginate 1544:1551 alginate 1544:1551 alginate 1544:1551 Significant adaptation to the growth environment of macroalgae includes the degradation of brown algae-derived diverse polysaccharides (alginate, laminarin and fucoidan). 36884369 12 116 theme respiratory 1284:1294 arg1 quinone 1296:1302 the sole respiratory quinone 1275:1302 the sole respiratory quinone 1275:1302 MK-6 is the sole respiratory quinone. 36884369 12 116 theme respiratory 1284:1294 arg1 MK-6 1267:1270 MK-6 1267:1270 MK-6 1267:1270 MK-6 is the sole respiratory quinone. 36884369 1 117 theme Tamlana 38:44 arg1 sargassicola 46:57 nov. and Tamlana sargassicola 29:57 nov. and Tamlana sargassicola 29:57 nov. and Tamlana sargassicola sp. 36884369 9 118 theme % 1079:1079 arg1 NaCl 1087:1090 0-4 % (w/v) NaCl 1075:1090 0-4 % (w/v) NaCl (optimum 0-1 %) 1075:1106 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 9 118 theme % 1079:1079 arg1 % 1105:1105 optimum 0-1 % 1093:1105 optimum 0-1 % 1093:1105 Growth of strains PT2-4T and 62-3T occurs at 15-40 °C (optimum, 30 °C) with 0-4 % (w/v) NaCl (optimum 0-1 %). 36884369 8 119 theme strain 905:910 arg1 62-3T 912:916 strain 62-3T 905:916 strain 62-3T 905:916 The highest DNA-DNA hybridization (DDH) value of strain PT2-4T was 35.2 % with strain 62-3T, while the DDH value of strain 62-3T was 37.7 % with T. sedimentorum JCM 19808T. 36884369 5 120 theme 16S 414:416 arg1 rRNA 418:421 16S rRNA 414:421 16S rRNA gene sequence analysis 414:444 16S rRNA gene sequence analysis showed that the closest described relative of strains PT2-4T and 62-3T is Tamlana sedimentorum JCM 19808T with 98.40 and 97.98% sequence similarity, respectively. 36884369 7 121 theme identity 743:750 arg1 % 780:780 87.34 and 88.97 % 764:780 87.34 and 88.97 % 764:780 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36884369 7 121 theme identity 743:750 arg1 values 752:757 the highest average nucleotide identity values 712:757 the highest average nucleotide identity values 712:757 Furthermore, the highest average nucleotide identity values were 87.34 and 88.97 % for strains PT2-4T and 62-3T, respectively. 36662050 8 0 from production 1315:1324 arg1 terms 1358:1362 terms 1358:1362 terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior 1358:1477 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 2 1 theme catechol 366:373 arg1 group 375:379 group 375:379 group 375:379 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 9 2 theme suitable 1568:1575 arg1 adhesives 1558:1566 new adhesives 1554:1566 new adhesives suitable for the regeneration of hard tissues 1554:1612 Considering the promising properties exhibited by the obtained membranes, new adhesives suitable for the regeneration of hard tissues can be envisaged. 36662050 0 3 theme Membranes 86:94 arg1 Development 48:58 the Development 44:58 the Development of Adhesive and Bioactive Membranes Envisaging Guided Tissue Regeneration 44:132 Exploiting Polyelectrolyte Complexation for the Development of Adhesive and Bioactive Membranes Envisaging Guided Tissue Regeneration. 36662050 8 4 theme mechanical 1411:1420 arg1 performance 1422:1432 mechanical performance 1411:1432 mechanical performance 1411:1432 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 8 5 theme in 1435:1436 arg1 bioactivity 1444:1454 in vitro bioactivity 1435:1454 in vitro bioactivity 1435:1454 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 0 6 theme Tissue 114:119 arg1 Regeneration 121:132 Guided Tissue Regeneration 107:132 Guided Tissue Regeneration 107:132 Exploiting Polyelectrolyte Complexation for the Development of Adhesive and Bioactive Membranes Envisaging Guided Tissue Regeneration. 36662050 7 7 theme polymers 1115:1122 arg1 combinations 1093:1104 combinations 1093:1104 combinations of these polymers modified with catechol groups 1093:1152 Moreover, combinations of these polymers modified with catechol groups were made to enhance the adhesive properties of the assembled membranes. 36662050 5 8 dep polymers 883:890 arg1 CHI 903:905 CHI 903:905 CHI 903:905 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 5 8 dep polymers 883:890 arg1 chitosan 893:900 chitosan 893:900 two natural and biocompatible polymers: chitosan (CHI) 853:906 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 8 9 theme stability 1400:1408 arg1 terms 1358:1362 terms 1358:1362 terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior 1358:1477 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 3 10 dep obtain 557:562 arg1 CoPEC 634:638 CoPEC 634:638 CoPEC 634:638 Inspired by such mussel bioadhesion, we demonstrate that catechol-modified polysaccharides can be used to obtain adhesive membranes using the compaction of polyelectrolyte complexes (CoPEC) method. 36662050 0 11 theme Guided 107:112 arg1 Regeneration 121:132 Guided Tissue Regeneration 107:132 Guided Tissue Regeneration 107:132 Exploiting Polyelectrolyte Complexation for the Development of Adhesive and Bioactive Membranes Envisaging Guided Tissue Regeneration. 36662050 7 12 theme catechol 1138:1145 arg1 groups 1147:1152 catechol groups 1138:1152 catechol groups 1138:1152 Moreover, combinations of these polymers modified with catechol groups were made to enhance the adhesive properties of the assembled membranes. 36662050 8 13 theme wettability 1387:1397 arg1 terms 1358:1362 terms 1358:1362 terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior 1358:1477 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 3 14 theme catechol-modified 508:524 arg1 polysaccharides 526:540 catechol-modified polysaccharides 508:540 catechol-modified polysaccharides 508:540 Inspired by such mussel bioadhesion, we demonstrate that catechol-modified polysaccharides can be used to obtain adhesive membranes using the compaction of polyelectrolyte complexes (CoPEC) method. 36662050 7 15 theme assembled 1206:1214 arg1 membranes 1216:1224 the assembled membranes 1202:1224 the assembled membranes 1202:1224 Moreover, combinations of these polymers modified with catechol groups were made to enhance the adhesive properties of the assembled membranes. 36662050 9 16 theme new 1554:1556 arg1 adhesives 1558:1566 new adhesives 1554:1566 new adhesives suitable for the regeneration of hard tissues 1554:1612 Considering the promising properties exhibited by the obtained membranes, new adhesives suitable for the regeneration of hard tissues can be envisaged. 36662050 5 17 theme biocompatible 869:881 arg1 polymers 883:890 two natural and biocompatible polymers 853:890 two natural and biocompatible polymers: chitosan (CHI) 853:906 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 5 17 theme biocompatible 869:881 arg1 polycation 913:922 a polycation 911:922 a polycation 911:922 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 5 17 theme biocompatible 869:881 arg1 polyanion 954:962 a polyanion 952:962 a polyanion 952:962 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 4 18 theme simple 657:662 arg1 It 649:650 It 649:650 It 649:650 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 4 18 theme simple 657:662 arg1 approach 678:685 a simple and versatile approach 655:685 a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature 655:842 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 3 19 theme adhesive 564:571 arg1 membranes 573:581 adhesive membranes 564:581 adhesive membranes using the compaction of polyelectrolyte complexes 564:631 Inspired by such mussel bioadhesion, we demonstrate that catechol-modified polysaccharides can be used to obtain adhesive membranes using the compaction of polyelectrolyte complexes (CoPEC) method. 36662050 3 20 theme such 463:466 arg1 bioadhesion 475:485 such mussel bioadhesion 463:485 such mussel bioadhesion 463:485 Inspired by such mussel bioadhesion, we demonstrate that catechol-modified polysaccharides can be used to obtain adhesive membranes using the compaction of polyelectrolyte complexes (CoPEC) method. 36662050 7 21 theme membranes 1216:1224 arg1 properties 1188:1197 the adhesive properties 1175:1197 the adhesive properties of the assembled membranes 1175:1224 Moreover, combinations of these polymers modified with catechol groups were made to enhance the adhesive properties of the assembled membranes. 36662050 8 22 theme morphology 1375:1384 arg1 terms 1358:1362 terms 1358:1362 terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior 1358:1477 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 8 23 theme composite 1329:1337 arg1 membranes 1345:1353 composite CoPEC membranes 1329:1353 composite CoPEC membranes 1329:1353 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 3 24 theme mussel 468:473 arg1 bioadhesion 475:485 such mussel bioadhesion 463:485 such mussel bioadhesion 463:485 Inspired by such mussel bioadhesion, we demonstrate that catechol-modified polysaccharides can be used to obtain adhesive membranes using the compaction of polyelectrolyte complexes (CoPEC) method. 36662050 0 25 theme Polyelectrolyte 11:25 arg1 Complexation 27:38 Polyelectrolyte Complexation 11:38 Polyelectrolyte Complexation 11:38 Exploiting Polyelectrolyte Complexation for the Development of Adhesive and Bioactive Membranes Envisaging Guided Tissue Regeneration. 36662050 8 26 theme behavior 1470:1477 arg1 terms 1358:1362 terms 1358:1362 terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior 1358:1477 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 3 27 theme polyelectrolyte 607:621 arg1 complexes 623:631 polyelectrolyte complexes 607:631 polyelectrolyte complexes 607:631 Inspired by such mussel bioadhesion, we demonstrate that catechol-modified polysaccharides can be used to obtain adhesive membranes using the compaction of polyelectrolyte complexes (CoPEC) method. 36662050 8 28 theme successful 1304:1313 arg1 production 1315:1324 the successful production 1300:1324 the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior 1300:1477 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 2 29 theme acid 318:321 arg1 DOPA 353:356 DOPA 353:356 DOPA 353:356 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 29 theme acid 318:321 arg1 L-3,4-dihydroxyphenylalanine 323:350 the peculiar amino acid L-3,4-dihydroxyphenylalanine 299:350 the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA) 299:357 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 4 30 theme polyelectrolyte 697:711 arg1 blocks 735:740 building blocks 726:740 building blocks that coalesce and dry as membrane constructs 726:785 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 4 30 theme polyelectrolyte 697:711 arg1 result 799:804 a result 797:804 a result of sedimentation and mild temperature 797:842 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 4 30 theme polyelectrolyte 697:711 arg1 complexes 713:721 polyelectrolyte complexes 697:721 polyelectrolyte complexes 697:721 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 7 31 theme adhesive 1179:1186 arg1 properties 1188:1197 the adhesive properties 1175:1197 the adhesive properties of the assembled membranes 1175:1224 Moreover, combinations of these polymers modified with catechol groups were made to enhance the adhesive properties of the assembled membranes. 36662050 4 32 theme membrane 767:774 arg1 constructs 776:785 membrane constructs 767:785 membrane constructs 767:785 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 8 33 theme Extensive 1227:1235 arg1 characterization 1254:1269 Extensive physico-chemical characterization 1227:1269 Extensive physico-chemical characterization 1227:1269 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 2 34 theme amino 312:316 arg1 DOPA 353:356 DOPA 353:356 DOPA 353:356 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 34 theme amino 312:316 arg1 L-3,4-dihydroxyphenylalanine 323:350 the peculiar amino acid L-3,4-dihydroxyphenylalanine 299:350 the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA) 299:357 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 9 35 theme obtained 1534:1541 arg1 membranes 1543:1551 the obtained membranes 1530:1551 the obtained membranes 1530:1551 Considering the promising properties exhibited by the obtained membranes, new adhesives suitable for the regeneration of hard tissues can be envisaged. 36662050 3 36 theme complexes 623:631 arg1 compaction 593:602 the compaction 589:602 the compaction of polyelectrolyte complexes 589:631 Inspired by such mussel bioadhesion, we demonstrate that catechol-modified polysaccharides can be used to obtain adhesive membranes using the compaction of polyelectrolyte complexes (CoPEC) method. 36662050 2 37 contain contain 291:297 arg2 L-3,4-dihydroxyphenylalanine 323:350 the peculiar amino acid L-3,4-dihydroxyphenylalanine 299:350 the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA) 299:357 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 37 contain contain 291:297 arg1 MAPs 285:288 MAPs 285:288 MAPs 285:288 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 37 contain contain 291:297 arg1 proteins 275:282 The secreted marine mussel adhesive proteins 239:282 The secreted marine mussel adhesive proteins (MAPs) 239:289 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 37 contain contain 291:297 arg2 DOPA 353:356 DOPA 353:356 DOPA 353:356 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 4 38 theme sedimentation 809:821 arg1 result 799:804 a result 797:804 a result of sedimentation and mild temperature 797:842 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 4 38 theme sedimentation 809:821 arg1 complexes 713:721 polyelectrolyte complexes 697:721 polyelectrolyte complexes 697:721 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 2 39 theme peculiar 303:310 arg1 DOPA 353:356 DOPA 353:356 DOPA 353:356 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 39 theme peculiar 303:310 arg1 L-3,4-dihydroxyphenylalanine 323:350 the peculiar amino acid L-3,4-dihydroxyphenylalanine 299:350 the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA) 299:357 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 9 40 theme hard 1601:1604 arg1 tissues 1606:1612 hard tissues 1601:1612 hard tissues 1601:1612 Considering the promising properties exhibited by the obtained membranes, new adhesives suitable for the regeneration of hard tissues can be envisaged. 36662050 1 41 theme other 211:215 arg1 organisms 217:225 other organisms 211:225 other organisms underwater 211:236 Mussels secrete protein-based byssal threads to tether to rocks, ships, and other organisms underwater. 36662050 8 42 theme CoPEC 1339:1343 arg1 membranes 1345:1353 composite CoPEC membranes 1329:1353 composite CoPEC membranes 1329:1353 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 2 43 theme marine 252:257 arg1 MAPs 285:288 MAPs 285:288 MAPs 285:288 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 43 theme marine 252:257 arg1 proteins 275:282 The secreted marine mussel adhesive proteins 239:282 The secreted marine mussel adhesive proteins (MAPs) 239:289 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 44 theme adhesive 430:437 arg1 properties 439:448 their outstanding adhesive properties 412:448 their outstanding adhesive properties 412:448 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 8 45 theme physico-chemical 1237:1252 arg1 characterization 1254:1269 Extensive physico-chemical characterization 1227:1269 Extensive physico-chemical characterization 1227:1269 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 2 46 theme secreted 243:250 arg1 MAPs 285:288 MAPs 285:288 MAPs 285:288 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 46 theme secreted 243:250 arg1 proteins 275:282 The secreted marine mussel adhesive proteins 239:282 The secreted marine mussel adhesive proteins (MAPs) 239:289 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 47 theme outstanding 418:428 arg1 properties 439:448 their outstanding adhesive properties 412:448 their outstanding adhesive properties 412:448 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 0 48 theme Adhesive 63:70 arg1 Membranes 86:94 Adhesive and Bioactive Membranes 63:94 Adhesive and Bioactive Membranes Envisaging Guided Tissue Regeneration 63:132 Exploiting Polyelectrolyte Complexation for the Development of Adhesive and Bioactive Membranes Envisaging Guided Tissue Regeneration. 36662050 6 49 theme nanoparticles 1040:1052 arg1 entrapment 1002:1011 the entrapment 998:1011 the entrapment of ternary bioactive glass nanoparticles 998:1052 The CoPEC technique also allowed the entrapment of ternary bioactive glass nanoparticles to stimulate mineralization. 36662050 6 50 theme CoPEC 969:973 arg1 technique 975:983 The CoPEC technique 965:983 The CoPEC technique 965:983 The CoPEC technique also allowed the entrapment of ternary bioactive glass nanoparticles to stimulate mineralization. 36662050 8 51 theme cellular 1461:1468 arg1 behavior 1470:1477 cellular behavior 1461:1477 cellular behavior 1461:1477 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 8 52 theme performance 1422:1432 arg1 terms 1358:1362 terms 1358:1362 terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior 1358:1477 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 5 53 theme hyaluronic 928:937 arg1 acid 939:942 hyaluronic acid 928:942 hyaluronic acid (HA) 928:947 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 5 53 theme hyaluronic 928:937 arg1 HA 945:946 HA 945:946 HA 945:946 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 9 54 theme tissues 1606:1612 arg1 regeneration 1585:1596 the regeneration 1581:1596 the regeneration of hard tissues 1581:1612 Considering the promising properties exhibited by the obtained membranes, new adhesives suitable for the regeneration of hard tissues can be envisaged. 36662050 9 55 theme promising 1496:1504 arg1 properties 1506:1515 the promising properties 1492:1515 the promising properties exhibited by the obtained membranes 1492:1551 Considering the promising properties exhibited by the obtained membranes, new adhesives suitable for the regeneration of hard tissues can be envisaged. 36662050 8 56 theme membranes 1345:1353 arg1 production 1315:1324 the successful production 1300:1324 the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior 1300:1477 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 4 57 theme temperature 832:842 arg1 result 799:804 a result 797:804 a result of sedimentation and mild temperature 797:842 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 4 57 theme temperature 832:842 arg1 complexes 713:721 polyelectrolyte complexes 697:721 polyelectrolyte complexes 697:721 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 5 58 used used 848:851 arg2 We 845:846 We 845:846 We 845:846 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 4 59 theme mild 827:830 arg1 temperature 832:842 mild temperature 827:842 mild temperature 827:842 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 3 60 used used 549:552 arg2 polysaccharides 526:540 catechol-modified polysaccharides 508:540 catechol-modified polysaccharides 508:540 Inspired by such mussel bioadhesion, we demonstrate that catechol-modified polysaccharides can be used to obtain adhesive membranes using the compaction of polyelectrolyte complexes (CoPEC) method. 36662050 8 61 theme bioactivity 1444:1454 arg1 terms 1358:1362 terms 1358:1362 terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior 1358:1477 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 1 62 theme protein-based 151:163 arg1 threads 172:178 protein-based byssal threads 151:178 protein-based byssal threads 151:178 Mussels secrete protein-based byssal threads to tether to rocks, ships, and other organisms underwater. 36662050 6 63 theme glass 1034:1038 arg1 nanoparticles 1040:1052 ternary bioactive glass nanoparticles 1016:1052 ternary bioactive glass nanoparticles 1016:1052 The CoPEC technique also allowed the entrapment of ternary bioactive glass nanoparticles to stimulate mineralization. 36662050 5 64 theme natural 857:863 arg1 polymers 883:890 two natural and biocompatible polymers 853:890 two natural and biocompatible polymers: chitosan (CHI) 853:906 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 5 64 theme natural 857:863 arg1 polycation 913:922 a polycation 911:922 a polycation 911:922 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 5 64 theme natural 857:863 arg1 polyanion 954:962 a polyanion 952:962 a polyanion 952:962 We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. 36662050 1 65 theme byssal 165:170 arg1 threads 172:178 protein-based byssal threads 151:178 protein-based byssal threads 151:178 Mussels secrete protein-based byssal threads to tether to rocks, ships, and other organisms underwater. 36662050 6 66 theme bioactive 1024:1032 arg1 nanoparticles 1040:1052 ternary bioactive glass nanoparticles 1016:1052 ternary bioactive glass nanoparticles 1016:1052 The CoPEC technique also allowed the entrapment of ternary bioactive glass nanoparticles to stimulate mineralization. 36662050 0 67 theme Bioactive 76:84 arg1 Membranes 86:94 Adhesive and Bioactive Membranes 63:94 Adhesive and Bioactive Membranes Envisaging Guided Tissue Regeneration 63:132 Exploiting Polyelectrolyte Complexation for the Development of Adhesive and Bioactive Membranes Envisaging Guided Tissue Regeneration. 36662050 4 68 theme versatile 668:676 arg1 It 649:650 It 649:650 It 649:650 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 4 68 theme versatile 668:676 arg1 approach 678:685 a simple and versatile approach 655:685 a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature 655:842 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 2 69 theme adhesive 266:273 arg1 MAPs 285:288 MAPs 285:288 MAPs 285:288 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 69 theme adhesive 266:273 arg1 proteins 275:282 The secreted marine mussel adhesive proteins 239:282 The secreted marine mussel adhesive proteins (MAPs) 239:289 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 4 70 theme building 726:733 arg1 blocks 735:740 building blocks 726:740 building blocks that coalesce and dry as membrane constructs 726:785 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 4 70 theme building 726:733 arg1 complexes 713:721 polyelectrolyte complexes 697:721 polyelectrolyte complexes 697:721 It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. 36662050 8 71 dep in 1435:1436 arg1 vitro 1438:1442 vitro 1438:1442 vitro 1438:1442 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36662050 6 72 theme ternary 1016:1022 arg1 nanoparticles 1040:1052 ternary bioactive glass nanoparticles 1016:1052 ternary bioactive glass nanoparticles 1016:1052 The CoPEC technique also allowed the entrapment of ternary bioactive glass nanoparticles to stimulate mineralization. 36662050 2 73 theme mussel 259:264 arg1 MAPs 285:288 MAPs 285:288 MAPs 285:288 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 2 73 theme mussel 259:264 arg1 proteins 275:282 The secreted marine mussel adhesive proteins 239:282 The secreted marine mussel adhesive proteins (MAPs) 239:289 The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. 36662050 8 74 theme surface 1367:1373 arg1 morphology 1375:1384 surface morphology 1367:1384 surface morphology 1367:1384 Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. 36850202 8 0 theme analyses 1297:1304 arg1 results 1272:1278 The results 1268:1278 The results of the performed analyses 1268:1304 The results of the performed analyses allowed us to confirm the presence of curcumin nano- and microcapsules in the alginate-chitosan composite. 36850202 1 1 theme global 266:271 arg1 goal 273:276 the global goal 262:276 the global goal 262:276 In the era of growing plastic consumption, food waste by consumers and overproduction caused by economic reasons, the global goal is to decrease these phenomena. 36850202 0 2 theme Films 94:98 arg1 Properties 67:76 Physicochemical and Microbiological Properties 31:76 Physicochemical and Microbiological Properties of Biocomposite Films 31:98 Formation and Investigation of Physicochemical and Microbiological Properties of Biocomposite Films Containing Turmeric Extract Nano/Microcapsules. 36850202 10 3 from parameters 1596:1605 arg1 tests 1610:1614 tests 1610:1614 tests of solubility 1610:1628 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 11 4 theme obtained 1696:1703 arg1 properties 1705:1714 The obtained properties 1692:1714 The obtained properties of the developed films 1692:1737 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 10 5 theme swelling 1656:1663 arg1 parameters 1596:1605 better parameters 1589:1605 better parameters in tests of solubility 1589:1628 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 10 5 theme swelling 1656:1663 arg1 degree 1646:1651 degree 1646:1651 degree of swelling and mechanical properties 1646:1689 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 7 6 theme produced 1215:1222 arg1 films 1224:1228 the produced films 1211:1228 the produced films 1211:1228 Microbiological tests were carried out to analyze the influence of the produced films on the development of microorganisms. 36850202 8 7 theme curcumin 1344:1351 arg1 nano- 1353:1357 curcumin nano- 1344:1357 curcumin nano- 1344:1357 The results of the performed analyses allowed us to confirm the presence of curcumin nano- and microcapsules in the alginate-chitosan composite. 36850202 11 8 theme films 1733:1737 arg1 properties 1705:1714 The obtained properties 1692:1714 The obtained properties of the developed films 1692:1737 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 0 9 theme Extract 120:126 arg1 Nano/Microcapsules 128:145 Turmeric Extract Nano/Microcapsules 111:145 Turmeric Extract Nano/Microcapsules 111:145 Formation and Investigation of Physicochemical and Microbiological Properties of Biocomposite Films Containing Turmeric Extract Nano/Microcapsules. 36850202 5 10 theme zeta 956:959 arg1 potential 961:969 zeta potential 956:969 zeta potential 956:969 Bionanocomposites were analyzed using UV-VIS, FTIR, photoluminescence spectroscopy and SEM microscopy, while contact angles, surface free energy, particle size (DLS) and zeta potential were determined. 36850202 10 11 with film 1530:1533 arg1 concentration 1552:1564 the highest concentration 1540:1564 the highest concentration of the capsules 1540:1580 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 4 12 theme biopolymer 641:650 arg1 films 652:656 innovative and flexible biopolymer films 617:656 innovative and flexible biopolymer films based on sodium alginate and chitosan 617:694 The aim of our study was to obtain innovative and flexible biopolymer films based on sodium alginate and chitosan, as well as to develop methods for generating nanocapsules with turmeric extract in them. 36850202 0 13 theme Turmeric 111:118 arg1 Nano/Microcapsules 128:145 Turmeric Extract Nano/Microcapsules 111:145 Turmeric Extract Nano/Microcapsules 111:145 Formation and Investigation of Physicochemical and Microbiological Properties of Biocomposite Films Containing Turmeric Extract Nano/Microcapsules. 36850202 5 14 theme surface 911:917 arg1 energy 924:929 surface free energy 911:929 surface free energy 911:929 Bionanocomposites were analyzed using UV-VIS, FTIR, photoluminescence spectroscopy and SEM microscopy, while contact angles, surface free energy, particle size (DLS) and zeta potential were determined. 36850202 7 15 theme films 1224:1228 arg1 influence 1198:1206 the influence 1194:1206 the influence of the produced films on the development of microorganisms 1194:1265 Microbiological tests were carried out to analyze the influence of the produced films on the development of microorganisms. 36850202 5 16 theme UV-VIS 824:829 arg1 spectroscopy 856:867 UV-VIS, FTIR, photoluminescence spectroscopy 824:867 UV-VIS, FTIR, photoluminescence spectroscopy 824:867 Bionanocomposites were analyzed using UV-VIS, FTIR, photoluminescence spectroscopy and SEM microscopy, while contact angles, surface free energy, particle size (DLS) and zeta potential were determined. 36850202 6 17 theme mechanical 992:1001 arg1 properties 1020:1029 The mechanical and colorimetric properties 988:1029 The mechanical and colorimetric properties of the produced films 988:1051 The mechanical and colorimetric properties of the produced films were investigated, and the water content, solubility and water absorption were determined. 36850202 6 18 theme produced 1038:1045 arg1 films 1047:1051 the produced films 1034:1051 the produced films 1034:1051 The mechanical and colorimetric properties of the produced films were investigated, and the water content, solubility and water absorption were determined. 36850202 1 19 theme food 191:194 arg1 waste 196:200 food waste 191:200 food waste by consumers 191:213 In the era of growing plastic consumption, food waste by consumers and overproduction caused by economic reasons, the global goal is to decrease these phenomena. 36850202 10 20 theme highest 1544:1550 arg1 concentration 1552:1564 the highest concentration 1540:1564 the highest concentration of the capsules 1540:1580 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 8 21 theme performed 1287:1295 arg1 analyses 1297:1304 the performed analyses 1283:1304 the performed analyses 1283:1304 The results of the performed analyses allowed us to confirm the presence of curcumin nano- and microcapsules in the alginate-chitosan composite. 36850202 10 22 theme mechanical 1669:1678 arg1 properties 1680:1689 mechanical properties 1669:1689 mechanical properties 1669:1689 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 8 23 theme microcapsules 1363:1375 arg1 presence 1332:1339 the presence 1328:1339 the presence of curcumin nano- and microcapsules in the alginate-chitosan composite 1328:1410 The results of the performed analyses allowed us to confirm the presence of curcumin nano- and microcapsules in the alginate-chitosan composite. 36850202 3 24 theme unique 458:463 arg1 properties 465:474 their unique properties 452:474 their unique properties 452:474 Due to their unique properties, they can be used in many areas of our life and reduce the constantly increasing pollution of our planet. 36850202 7 25 theme Microbiological 1144:1158 arg1 tests 1160:1164 Microbiological tests 1144:1164 Microbiological tests 1144:1164 Microbiological tests were carried out to analyze the influence of the produced films on the development of microorganisms. 36850202 8 26 theme alginate-chitosan 1384:1400 arg1 composite 1402:1410 the alginate-chitosan composite 1380:1410 the alginate-chitosan composite 1380:1410 The results of the performed analyses allowed us to confirm the presence of curcumin nano- and microcapsules in the alginate-chitosan composite. 36850202 5 27 theme free 919:922 arg1 energy 924:929 surface free energy 911:929 surface free energy 911:929 Bionanocomposites were analyzed using UV-VIS, FTIR, photoluminescence spectroscopy and SEM microscopy, while contact angles, surface free energy, particle size (DLS) and zeta potential were determined. 36850202 2 28 theme ecological 399:408 arg1 packaging 434:442 ecological, intelligent and active packaging 399:442 ecological, intelligent and active packaging 399:442 Biocomposite films investigated in the past years are creating a promising future toward ecological, intelligent and active packaging. 36850202 10 29 theme better 1589:1594 arg1 content 1637:1643 water content 1631:1643 water content 1631:1643 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 10 29 theme better 1589:1594 arg1 parameters 1596:1605 better parameters 1589:1605 better parameters in tests of solubility 1589:1628 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 10 29 theme better 1589:1594 arg1 degree 1646:1651 degree 1646:1651 degree of swelling and mechanical properties 1646:1689 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 11 30 theme intelligent 1775:1785 arg1 them 1745:1748 them 1745:1748 them 1745:1748 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 11 30 theme intelligent 1775:1785 arg1 materials 1797:1805 active and intelligent packaging materials 1764:1805 active and intelligent packaging materials 1764:1805 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 9 31 theme capsule 1503:1509 arg1 manufacturing 1511:1523 capsule manufacturing 1503:1523 capsule manufacturing 1503:1523 Moreover, studies have shown that the structure of polysaccharides does not change during capsule manufacturing. 36850202 6 32 theme films 1047:1051 arg1 properties 1020:1029 The mechanical and colorimetric properties 988:1029 The mechanical and colorimetric properties of the produced films 988:1051 The mechanical and colorimetric properties of the produced films were investigated, and the water content, solubility and water absorption were determined. 36850202 10 33 theme water 1631:1635 arg1 content 1637:1643 water content 1631:1643 water content 1631:1643 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 10 33 theme water 1631:1635 arg1 parameters 1596:1605 better parameters 1589:1605 better parameters in tests of solubility 1589:1628 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 3 34 theme increasing 546:555 arg1 pollution 557:565 the constantly increasing pollution 531:565 the constantly increasing pollution of our planet 531:579 Due to their unique properties, they can be used in many areas of our life and reduce the constantly increasing pollution of our planet. 36850202 5 35 theme particle 932:939 arg1 DLS 947:949 DLS 947:949 DLS 947:949 Bionanocomposites were analyzed using UV-VIS, FTIR, photoluminescence spectroscopy and SEM microscopy, while contact angles, surface free energy, particle size (DLS) and zeta potential were determined. 36850202 5 35 theme particle 932:939 arg1 size 941:944 particle size 932:944 particle size (DLS) 932:950 Bionanocomposites were analyzed using UV-VIS, FTIR, photoluminescence spectroscopy and SEM microscopy, while contact angles, surface free energy, particle size (DLS) and zeta potential were determined. 36850202 6 36 theme water 1080:1084 arg1 content 1086:1092 the water content 1076:1092 the water content 1076:1092 The mechanical and colorimetric properties of the produced films were investigated, and the water content, solubility and water absorption were determined. 36850202 11 37 theme active 1764:1769 arg1 them 1745:1748 them 1745:1748 them 1745:1748 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 11 37 theme active 1764:1769 arg1 materials 1797:1805 active and intelligent packaging materials 1764:1805 active and intelligent packaging materials 1764:1805 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 2 38 theme Biocomposite 310:321 arg1 films 323:327 Biocomposite films 310:327 Biocomposite films investigated in the past years 310:358 Biocomposite films investigated in the past years are creating a promising future toward ecological, intelligent and active packaging. 36850202 5 39 theme SEM 873:875 arg1 microscopy 877:886 SEM microscopy 873:886 SEM microscopy 873:886 Bionanocomposites were analyzed using UV-VIS, FTIR, photoluminescence spectroscopy and SEM microscopy, while contact angles, surface free energy, particle size (DLS) and zeta potential were determined. 36850202 10 40 theme solubility 1619:1628 arg1 tests 1610:1614 tests 1610:1614 tests of solubility 1610:1628 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 7 41 theme microorganisms 1252:1265 arg1 development 1237:1247 the development 1233:1247 the development of microorganisms 1233:1265 Microbiological tests were carried out to analyze the influence of the produced films on the development of microorganisms. 36850202 8 42 from presence 1332:1339 arg1 composite 1402:1410 the alginate-chitosan composite 1380:1410 the alginate-chitosan composite 1380:1410 The results of the performed analyses allowed us to confirm the presence of curcumin nano- and microcapsules in the alginate-chitosan composite. 36850202 6 43 theme colorimetric 1007:1018 arg1 properties 1020:1029 The mechanical and colorimetric properties 988:1029 The mechanical and colorimetric properties of the produced films 988:1051 The mechanical and colorimetric properties of the produced films were investigated, and the water content, solubility and water absorption were determined. 36850202 3 44 used used 489:492 arg2 they 477:480 they 477:480 they 477:480 Due to their unique properties, they can be used in many areas of our life and reduce the constantly increasing pollution of our planet. 36850202 2 45 theme active 427:432 arg1 packaging 434:442 ecological, intelligent and active packaging 399:442 ecological, intelligent and active packaging 399:442 Biocomposite films investigated in the past years are creating a promising future toward ecological, intelligent and active packaging. 36850202 0 46 theme Physicochemical 31:45 arg1 Properties 67:76 Physicochemical and Microbiological Properties 31:76 Physicochemical and Microbiological Properties of Biocomposite Films 31:98 Formation and Investigation of Physicochemical and Microbiological Properties of Biocomposite Films Containing Turmeric Extract Nano/Microcapsules. 36850202 4 47 theme innovative 617:626 arg1 films 652:656 innovative and flexible biopolymer films 617:656 innovative and flexible biopolymer films based on sodium alginate and chitosan 617:694 The aim of our study was to obtain innovative and flexible biopolymer films based on sodium alginate and chitosan, as well as to develop methods for generating nanocapsules with turmeric extract in them. 36850202 0 48 theme Properties 67:76 arg1 Investigation 14:26 Investigation 14:26 Investigation 14:26 Formation and Investigation of Physicochemical and Microbiological Properties of Biocomposite Films Containing Turmeric Extract Nano/Microcapsules. 36850202 0 48 theme Properties 67:76 arg1 Formation 0:8 Formation 0:8 Formation 0:8 Formation and Investigation of Physicochemical and Microbiological Properties of Biocomposite Films Containing Turmeric Extract Nano/Microcapsules. 36850202 8 49 attach presence 1332:1339 arg2 nano- 1353:1357 curcumin nano- 1344:1357 curcumin nano- 1344:1357 The results of the performed analyses allowed us to confirm the presence of curcumin nano- and microcapsules in the alginate-chitosan composite. 36850202 8 49 attach presence 1332:1339 arg1 composite 1402:1410 the alginate-chitosan composite 1380:1410 the alginate-chitosan composite 1380:1410 The results of the performed analyses allowed us to confirm the presence of curcumin nano- and microcapsules in the alginate-chitosan composite. 36850202 8 49 attach presence 1332:1339 arg2 microcapsules 1363:1375 microcapsules 1363:1375 microcapsules 1363:1375 The results of the performed analyses allowed us to confirm the presence of curcumin nano- and microcapsules in the alginate-chitosan composite. 36850202 10 50 theme capsules 1573:1580 arg1 concentration 1552:1564 the highest concentration 1540:1564 the highest concentration of the capsules 1540:1580 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 3 51 theme planet 574:579 arg1 pollution 557:565 the constantly increasing pollution 531:565 the constantly increasing pollution of our planet 531:579 Due to their unique properties, they can be used in many areas of our life and reduce the constantly increasing pollution of our planet. 36850202 5 52 theme contact 895:901 arg1 angles 903:908 contact angles 895:908 contact angles 895:908 Bionanocomposites were analyzed using UV-VIS, FTIR, photoluminescence spectroscopy and SEM microscopy, while contact angles, surface free energy, particle size (DLS) and zeta potential were determined. 36850202 0 53 theme Microbiological 51:65 arg1 Properties 67:76 Physicochemical and Microbiological Properties 31:76 Physicochemical and Microbiological Properties of Biocomposite Films 31:98 Formation and Investigation of Physicochemical and Microbiological Properties of Biocomposite Films Containing Turmeric Extract Nano/Microcapsules. 36850202 2 54 theme intelligent 411:421 arg1 packaging 434:442 ecological, intelligent and active packaging 399:442 ecological, intelligent and active packaging 399:442 Biocomposite films investigated in the past years are creating a promising future toward ecological, intelligent and active packaging. 36850202 9 55 theme polysaccharides 1464:1478 arg1 structure 1451:1459 the structure 1447:1459 the structure of polysaccharides 1447:1478 Moreover, studies have shown that the structure of polysaccharides does not change during capsule manufacturing. 36850202 3 56 theme many 497:500 arg1 areas 502:506 many areas 497:506 many areas of our life 497:518 Due to their unique properties, they can be used in many areas of our life and reduce the constantly increasing pollution of our planet. 36850202 2 57 theme past 349:352 arg1 years 354:358 the past years 345:358 the past years 345:358 Biocomposite films investigated in the past years are creating a promising future toward ecological, intelligent and active packaging. 36850202 6 58 theme water 1110:1114 arg1 absorption 1116:1125 water absorption 1110:1125 water absorption 1110:1125 The mechanical and colorimetric properties of the produced films were investigated, and the water content, solubility and water absorption were determined. 36850202 1 59 theme economic 244:251 arg1 reasons 253:259 economic reasons 244:259 economic reasons 244:259 In the era of growing plastic consumption, food waste by consumers and overproduction caused by economic reasons, the global goal is to decrease these phenomena. 36850202 11 60 used used 1756:1759 arg2 them 1745:1748 them 1745:1748 them 1745:1748 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 11 60 used used 1756:1759 arg2 materials 1797:1805 active and intelligent packaging materials 1764:1805 active and intelligent packaging materials 1764:1805 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 11 60 used used 1756:1759 arg2 parts 1820:1824 their parts 1814:1824 their parts 1814:1824 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 7 61 from influence 1198:1206 arg1 development 1237:1247 the development 1233:1247 the development of microorganisms 1233:1265 Microbiological tests were carried out to analyze the influence of the produced films on the development of microorganisms. 36850202 4 62 theme turmeric 760:767 arg1 extract 769:775 turmeric extract 760:775 turmeric extract in them 760:783 The aim of our study was to obtain innovative and flexible biopolymer films based on sodium alginate and chitosan, as well as to develop methods for generating nanocapsules with turmeric extract in them. 36850202 11 63 theme packaging 1787:1795 arg1 them 1745:1748 them 1745:1748 them 1745:1748 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 11 63 theme packaging 1787:1795 arg1 materials 1797:1805 active and intelligent packaging materials 1764:1805 active and intelligent packaging materials 1764:1805 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 1 64 theme plastic 170:176 arg1 consumption 178:188 plastic consumption 170:188 plastic consumption 170:188 In the era of growing plastic consumption, food waste by consumers and overproduction caused by economic reasons, the global goal is to decrease these phenomena. 36850202 10 65 theme properties 1680:1689 arg1 parameters 1596:1605 better parameters 1589:1605 better parameters in tests of solubility 1589:1628 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 10 65 theme properties 1680:1689 arg1 degree 1646:1651 degree 1646:1651 degree of swelling and mechanical properties 1646:1689 The film with the highest concentration of the capsules showed better parameters in tests of solubility, water content, degree of swelling and mechanical properties. 36850202 0 66 theme Biocomposite 81:92 arg1 Films 94:98 Biocomposite Films 81:98 Biocomposite Films 81:98 Formation and Investigation of Physicochemical and Microbiological Properties of Biocomposite Films Containing Turmeric Extract Nano/Microcapsules. 36850202 8 67 theme nano- 1353:1357 arg1 presence 1332:1339 the presence 1328:1339 the presence of curcumin nano- and microcapsules in the alginate-chitosan composite 1328:1410 The results of the performed analyses allowed us to confirm the presence of curcumin nano- and microcapsules in the alginate-chitosan composite. 36850202 4 68 theme sodium 667:672 arg1 alginate 674:681 sodium alginate 667:681 sodium alginate 667:681 The aim of our study was to obtain innovative and flexible biopolymer films based on sodium alginate and chitosan, as well as to develop methods for generating nanocapsules with turmeric extract in them. 36850202 4 69 theme flexible 632:639 arg1 films 652:656 innovative and flexible biopolymer films 617:656 innovative and flexible biopolymer films based on sodium alginate and chitosan 617:694 The aim of our study was to obtain innovative and flexible biopolymer films based on sodium alginate and chitosan, as well as to develop methods for generating nanocapsules with turmeric extract in them. 36850202 11 70 theme developed 1723:1731 arg1 films 1733:1737 the developed films 1719:1737 the developed films 1719:1737 The obtained properties of the developed films allow them to be used as active and intelligent packaging materials, or as their parts. 36850202 5 71 dep UV-VIS 824:829 arg1 photoluminescence 838:854 photoluminescence 838:854 photoluminescence 838:854 Bionanocomposites were analyzed using UV-VIS, FTIR, photoluminescence spectroscopy and SEM microscopy, while contact angles, surface free energy, particle size (DLS) and zeta potential were determined. 36850202 5 71 dep UV-VIS 824:829 arg1 FTIR 832:835 FTIR 832:835 FTIR 832:835 Bionanocomposites were analyzed using UV-VIS, FTIR, photoluminescence spectroscopy and SEM microscopy, while contact angles, surface free energy, particle size (DLS) and zeta potential were determined. 36850202 4 72 from extract 769:775 arg1 them 780:783 them 780:783 them 780:783 The aim of our study was to obtain innovative and flexible biopolymer films based on sodium alginate and chitosan, as well as to develop methods for generating nanocapsules with turmeric extract in them. 36850202 3 73 theme life 515:518 arg1 areas 502:506 many areas 497:506 many areas of our life 497:518 Due to their unique properties, they can be used in many areas of our life and reduce the constantly increasing pollution of our planet. 36850202 4 74 theme study 597:601 arg1 aim 586:588 The aim 582:588 The aim of our study 582:601 The aim of our study was to obtain innovative and flexible biopolymer films based on sodium alginate and chitosan, as well as to develop methods for generating nanocapsules with turmeric extract in them. 36377581 4 0 theme aged 611:614 arg1 group 605:609 the old-old group 593:609 the old-old group aged 75 years and older (≥75 years group; n=199) 593:658 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 4 0 theme aged 611:614 arg1 group 646:650 ≥75 years group 636:650 ≥75 years group 636:650 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 7 1 theme positive 1023:1030 arg1 associations 1032:1043 significant positive associations 1011:1043 significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health 1011:1215 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 1 2 theme composition 139:149 arg1 driver 114:119 a major driver 106:119 a major driver of gut microbiota composition 106:149 Diet is considered as a major driver of gut microbiota composition. 36377581 1 2 theme composition 139:149 arg1 Diet 84:87 Diet 84:87 Diet 84:87 Diet is considered as a major driver of gut microbiota composition. 36377581 4 3 theme aged 544:547 arg1 group 538:542 the young-old group 524:542 the young-old group aged 65 to 74 years (<75 years group; n=246) 524:587 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 3 4 theme Quantitative 295:306 arg1 Index 308:312 the Quantitative Index 291:312 the Quantitative Index for Dietary Diversity (QUANTIDD) 291:345 Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. 36377581 9 5 theme groups 1445:1450 arg1 indices 1398:1404 QUANTIDD and α-diversity indices 1373:1404 QUANTIDD and α-diversity indices 1373:1404 Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. 36377581 9 5 theme groups 1445:1450 arg1 abundance 1413:1421 the abundance 1409:1421 the abundance of specific bacterial groups 1409:1450 Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. 36377581 5 6 theme species 809:815 arg1 distribution 817:828 species distribution 809:828 species distribution 809:828 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 6 7 theme uniform 896:902 arg1 abundance 904:912 a more uniform abundance 889:912 a more uniform abundance of various bacterial groups 889:940 This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. 36377581 9 8 theme years 1534:1538 arg1 group 1540:1544 the ≥75 years group 1526:1544 the ≥75 years group 1526:1544 Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. 36377581 7 9 dep Eubacterium 1081:1091 arg1 eligens 1093:1099 eligens 1093:1099 eligens 1093:1099 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 8 10 theme inflammatory 1313:1324 arg1 polysaccharides 1326:1340 inflammatory polysaccharides 1313:1340 inflammatory polysaccharides 1313:1340 Negative association was found with the abundance of Ruminococcus gnavus group, which produces inflammatory polysaccharides. 36377581 10 11 theme SCFAs-producing 1672:1686 arg1 bacteria 1688:1695 SCFAs-producing bacteria 1672:1695 SCFAs-producing bacteria 1672:1695 Our results suggest that dietary diversity contributes to the diversity of the gut microbiota and increases the abundance of SCFAs-producing bacteria, but only up to a certain age. 36377581 8 12 theme gnavus 1284:1289 arg1 group 1291:1295 Ruminococcus gnavus group 1271:1295 Ruminococcus gnavus group 1271:1295 Negative association was found with the abundance of Ruminococcus gnavus group, which produces inflammatory polysaccharides. 36377581 9 13 theme Positive 1343:1350 arg1 associations 1352:1363 Positive associations 1343:1363 Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups 1343:1450 Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. 36377581 7 14 theme Eubacterium 1112:1122 arg1 group 1135:1139 Eubacterium ventriosum group 1112:1139 Eubacterium ventriosum group 1112:1139 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 0 15 from diversity 58:66 arg1 elderly 75:81 elderly 75:81 elderly 75:81 Relationships between dietary diversity and gut microbial diversity in the elderly. 36377581 7 16 theme significant 1011:1021 arg1 associations 1032:1043 significant positive associations 1011:1043 significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health 1011:1215 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 7 17 theme short-chain 1156:1166 arg1 SCFAs 1181:1185 SCFAs 1181:1185 SCFAs 1181:1185 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 7 17 theme short-chain 1156:1166 arg1 acids 1174:1178 short-chain fatty acids 1156:1178 short-chain fatty acids (SCFAs) 1156:1186 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 10 18 theme microbiota 1630:1639 arg1 diversity 1609:1617 the diversity 1605:1617 the diversity of the gut microbiota 1605:1639 Our results suggest that dietary diversity contributes to the diversity of the gut microbiota and increases the abundance of SCFAs-producing bacteria, but only up to a certain age. 36377581 5 19 theme α-diversity 760:770 arg1 relationships 698:710 significant positive relationships 677:710 significant positive relationships with Pielou's evenness and Shannon indices 677:753 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 5 19 theme α-diversity 760:770 arg1 indices 772:778 two α-diversity indices 756:778 two α-diversity indices related to the uniformity of species distribution 756:828 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 3 20 theme Dietary 318:324 arg1 Diversity 326:334 Dietary Diversity 318:334 Dietary Diversity (QUANTIDD) 318:345 Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. 36377581 3 20 theme Dietary 318:324 arg1 QUANTIDD 337:344 QUANTIDD 337:344 QUANTIDD 337:344 Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. 36377581 5 21 theme distribution 817:828 arg1 uniformity 795:804 the uniformity 791:804 the uniformity of species distribution 791:828 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 6 22 theme gut 976:978 arg1 bacteria 980:987 gut bacteria 976:987 gut bacteria 976:987 This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. 36377581 11 23 theme specific 1842:1849 arg1 interventions 1859:1871 specific dietary interventions 1842:1871 specific dietary interventions 1842:1871 These findings help to understand the complex relationship between diet and gut microbiota, and provide hints for specific dietary interventions to promote beneficial gut microbiota in the elderly. 36377581 5 24 theme related 780:786 arg1 relationships 698:710 significant positive relationships 677:710 significant positive relationships with Pielou's evenness and Shannon indices 677:753 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 5 24 theme related 780:786 arg1 indices 772:778 two α-diversity indices 756:778 two α-diversity indices related to the uniformity of species distribution 756:828 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 3 25 theme gut 408:410 arg1 diversity 423:431 gut microbiota diversity 408:431 gut microbiota diversity 408:431 Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. 36377581 5 26 theme significant 677:687 arg1 relationships 698:710 significant positive relationships 677:710 significant positive relationships with Pielou's evenness and Shannon indices 677:753 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 5 26 theme significant 677:687 arg1 indices 772:778 two α-diversity indices 756:778 two α-diversity indices related to the uniformity of species distribution 756:828 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 7 27 with associations 1032:1043 arg1 abundance 1054:1062 the abundance 1050:1062 the abundance 1050:1062 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 7 27 with associations 1032:1043 arg1 beneficial 1196:1205 beneficial 1196:1205 beneficial 1196:1205 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 3 28 theme microbiota 412:421 arg1 diversity 423:431 gut microbiota diversity 408:431 gut microbiota diversity 408:431 Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. 36377581 7 29 theme Eubacterium 1081:1091 arg1 group 1101:1105 Eubacterium eligens group 1081:1105 Eubacterium eligens group 1081:1105 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 7 30 theme group 1135:1139 arg1 abundance 1054:1062 the abundance 1050:1062 the abundance 1050:1062 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 7 30 theme group 1135:1139 arg1 beneficial 1196:1205 beneficial 1196:1205 beneficial 1196:1205 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 8 31 theme Ruminococcus 1271:1282 arg1 group 1291:1295 Ruminococcus gnavus group 1271:1295 Ruminococcus gnavus group 1271:1295 Negative association was found with the abundance of Ruminococcus gnavus group, which produces inflammatory polysaccharides. 36377581 4 32 theme old-old 597:603 arg1 group 605:609 the old-old group 593:609 the old-old group aged 75 years and older (≥75 years group; n=199) 593:658 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 4 32 theme old-old 597:603 arg1 group 646:650 ≥75 years group 636:650 ≥75 years group 636:650 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 4 33 theme years 640:644 arg1 group 605:609 the old-old group 593:609 the old-old group aged 75 years and older (≥75 years group; n=199) 593:658 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 4 33 theme years 640:644 arg1 group 646:650 ≥75 years group 636:650 ≥75 years group 636:650 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 6 34 theme greater 957:963 arg1 variety 965:971 a greater variety 955:971 a greater variety of gut bacteria 955:987 This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. 36377581 6 34 theme greater 957:963 arg1 bacteria 980:987 gut bacteria 976:987 gut bacteria 976:987 This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. 36377581 7 35 theme Anaerostipes 1067:1078 arg1 abundance 1054:1062 the abundance 1050:1062 the abundance 1050:1062 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 7 35 theme Anaerostipes 1067:1078 arg1 beneficial 1196:1205 beneficial 1196:1205 beneficial 1196:1205 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 11 36 theme gut 1804:1806 arg1 microbiota 1808:1817 gut microbiota 1804:1817 gut microbiota 1804:1817 These findings help to understand the complex relationship between diet and gut microbiota, and provide hints for specific dietary interventions to promote beneficial gut microbiota in the elderly. 36377581 8 37 theme group 1291:1295 arg1 abundance 1258:1266 the abundance 1254:1266 the abundance 1254:1266 Negative association was found with the abundance of Ruminococcus gnavus group, which produces inflammatory polysaccharides. 36377581 4 38 theme group 575:579 arg1 years 558:562 65 to 74 years 549:562 65 to 74 years (<75 years group; n=246) 549:587 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 4 38 theme group 575:579 arg1 years 569:573 <75 years 565:573 <75 years group; n=246 565:586 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 0 39 theme dietary 22:28 arg1 diversity 30:38 dietary diversity 22:38 dietary diversity 22:38 Relationships between dietary diversity and gut microbial diversity in the elderly. 36377581 4 40 theme young-old 528:536 arg1 group 538:542 the young-old group 524:542 the young-old group aged 65 to 74 years (<75 years group; n=246) 524:587 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 9 41 theme bacterial 1435:1443 arg1 groups 1445:1450 specific bacterial groups 1426:1450 specific bacterial groups 1426:1450 Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. 36377581 6 42 theme bacteria 980:987 arg1 variety 965:971 a greater variety 955:971 a greater variety of gut bacteria 955:987 This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. 36377581 6 42 theme bacteria 980:987 arg1 bacteria 980:987 gut bacteria 976:987 gut bacteria 976:987 This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. 36377581 3 43 theme Japanese 440:447 arg1 subjects 449:456 445 Japanese subjects 436:456 445 Japanese subjects aged 65-90 years 436:473 Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. 36377581 0 44 theme gut 44:46 arg1 diversity 58:66 gut microbial diversity 44:66 gut microbial diversity 44:66 Relationships between dietary diversity and gut microbial diversity in the elderly. 36377581 9 45 theme specific 1426:1433 arg1 groups 1445:1450 specific bacterial groups 1426:1450 specific bacterial groups 1426:1450 Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. 36377581 7 46 theme group 1101:1105 arg1 abundance 1054:1062 the abundance 1050:1062 the abundance 1050:1062 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 7 46 theme group 1101:1105 arg1 beneficial 1196:1205 beneficial 1196:1205 beneficial 1196:1205 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 7 47 theme fatty 1168:1172 arg1 SCFAs 1181:1185 SCFAs 1181:1185 SCFAs 1181:1185 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 7 47 theme fatty 1168:1172 arg1 acids 1174:1178 short-chain fatty acids 1156:1178 short-chain fatty acids (SCFAs) 1156:1186 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 10 48 theme certain 1715:1721 arg1 age 1723:1725 a certain age 1713:1725 a certain age 1713:1725 Our results suggest that dietary diversity contributes to the diversity of the gut microbiota and increases the abundance of SCFAs-producing bacteria, but only up to a certain age. 36377581 9 49 theme α-diversity 1386:1396 arg1 indices 1398:1404 QUANTIDD and α-diversity indices 1373:1404 QUANTIDD and α-diversity indices 1373:1404 Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. 36377581 3 50 theme dietary 386:392 arg1 diversity 394:402 dietary diversity 386:402 dietary diversity 386:402 Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. 36377581 6 51 theme diverse 857:863 arg1 diet 865:868 a more diverse diet 850:868 a more diverse diet 850:868 This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. 36377581 5 52 theme positive 689:696 arg1 relationships 698:710 significant positive relationships 677:710 significant positive relationships with Pielou's evenness and Shannon indices 677:753 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 5 52 theme positive 689:696 arg1 indices 772:778 two α-diversity indices 756:778 two α-diversity indices related to the uniformity of species distribution 756:828 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 4 53 dep aged 544:547 arg1 years 558:562 65 to 74 years 549:562 65 to 74 years (<75 years group; n=246) 549:587 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 4 53 dep aged 544:547 arg1 years 569:573 <75 years 565:573 <75 years group; n=246 565:586 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 2 54 theme dietary 216:222 arg1 balance 224:230 overall dietary balance 208:230 overall dietary balance 208:230 However, little is known about the relationship between overall dietary balance and gut microbiota, especially in the elderly. 36377581 3 55 from diversity 423:431 arg1 subjects 449:456 445 Japanese subjects 436:456 445 Japanese subjects aged 65-90 years 436:473 Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. 36377581 10 56 theme dietary 1572:1578 arg1 diversity 1580:1588 dietary diversity 1572:1588 dietary diversity 1572:1588 Our results suggest that dietary diversity contributes to the diversity of the gut microbiota and increases the abundance of SCFAs-producing bacteria, but only up to a certain age. 36377581 9 57 theme QUANTIDD 1373:1380 arg1 indices 1398:1404 QUANTIDD and α-diversity indices 1373:1404 QUANTIDD and α-diversity indices 1373:1404 Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. 36377581 2 58 theme overall 208:214 arg1 balance 224:230 overall dietary balance 208:230 overall dietary balance 208:230 However, little is known about the relationship between overall dietary balance and gut microbiota, especially in the elderly. 36377581 4 59 theme older 629:633 arg1 group 605:609 the old-old group 593:609 the old-old group aged 75 years and older (≥75 years group; n=199) 593:658 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 4 59 theme older 629:633 arg1 group 646:650 ≥75 years group 636:650 ≥75 years group 636:650 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 0 60 theme microbial 48:56 arg1 diversity 58:66 gut microbial diversity 44:66 gut microbial diversity 44:66 Relationships between dietary diversity and gut microbial diversity in the elderly. 36377581 4 61 theme age 507:509 arg1 effect 497:502 the effect 493:502 the effect of age 493:509 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 11 62 theme dietary 1851:1857 arg1 interventions 1859:1871 specific dietary interventions 1842:1871 specific dietary interventions 1842:1871 These findings help to understand the complex relationship between diet and gut microbiota, and provide hints for specific dietary interventions to promote beneficial gut microbiota in the elderly. 36377581 1 63 theme major 108:112 arg1 driver 114:119 a major driver 106:119 a major driver of gut microbiota composition 106:149 Diet is considered as a major driver of gut microbiota composition. 36377581 1 63 theme major 108:112 arg1 Diet 84:87 Diet 84:87 Diet 84:87 Diet is considered as a major driver of gut microbiota composition. 36377581 10 64 theme bacteria 1688:1695 arg1 abundance 1659:1667 the abundance 1655:1667 the abundance of SCFAs-producing bacteria 1655:1695 Our results suggest that dietary diversity contributes to the diversity of the gut microbiota and increases the abundance of SCFAs-producing bacteria, but only up to a certain age. 36377581 11 65 theme beneficial 1884:1893 arg1 microbiota 1899:1908 beneficial gut microbiota 1884:1908 beneficial gut microbiota 1884:1908 These findings help to understand the complex relationship between diet and gut microbiota, and provide hints for specific dietary interventions to promote beneficial gut microbiota in the elderly. 36377581 11 66 theme gut 1895:1897 arg1 microbiota 1899:1908 beneficial gut microbiota 1884:1908 beneficial gut microbiota 1884:1908 These findings help to understand the complex relationship between diet and gut microbiota, and provide hints for specific dietary interventions to promote beneficial gut microbiota in the elderly. 36377581 4 67 dep group 646:650 arg1 n=199 653:657 n=199 653:657 n=199 653:657 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 6 68 theme groups 935:940 arg1 abundance 904:912 a more uniform abundance 889:912 a more uniform abundance of various bacterial groups 889:940 This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. 36377581 7 69 dep Eubacterium 1112:1122 arg1 ventriosum 1124:1133 ventriosum 1124:1133 ventriosum 1124:1133 QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. 36377581 8 70 theme Negative 1218:1225 arg1 association 1227:1237 Negative association 1218:1237 Negative association 1218:1237 Negative association was found with the abundance of Ruminococcus gnavus group, which produces inflammatory polysaccharides. 36377581 3 71 from diversity 394:402 arg1 subjects 449:456 445 Japanese subjects 436:456 445 Japanese subjects aged 65-90 years 436:473 Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. 36377581 3 72 theme aged 458:461 arg1 subjects 449:456 445 Japanese subjects 436:456 445 Japanese subjects aged 65-90 years 436:473 Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. 36377581 6 73 theme bacterial 925:933 arg1 groups 935:940 various bacterial groups 917:940 various bacterial groups 917:940 This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. 36377581 11 74 theme complex 1766:1772 arg1 relationship 1774:1785 the complex relationship 1762:1785 the complex relationship between diet and gut microbiota 1762:1817 These findings help to understand the complex relationship between diet and gut microbiota, and provide hints for specific dietary interventions to promote beneficial gut microbiota in the elderly. 36377581 4 75 dep 74 555:556 arg1 to 552:553 to 552:553 to 552:553 We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). 36377581 2 76 theme gut 236:238 arg1 microbiota 240:249 gut microbiota 236:249 gut microbiota 236:249 However, little is known about the relationship between overall dietary balance and gut microbiota, especially in the elderly. 36377581 5 77 theme Shannon 739:745 arg1 indices 747:753 Shannon indices 739:753 Shannon indices 739:753 QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. 36377581 1 78 theme gut 124:126 arg1 composition 139:149 gut microbiota composition 124:149 gut microbiota composition 124:149 Diet is considered as a major driver of gut microbiota composition. 36377581 9 79 theme years 1502:1506 arg1 group 1508:1512 the <75 years group 1494:1512 the <75 years group 1494:1512 Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. 36377581 6 80 theme various 917:923 arg1 groups 935:940 various bacterial groups 917:940 various bacterial groups 917:940 This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. 36377581 0 81 from diversity 30:38 arg1 elderly 75:81 elderly 75:81 elderly 75:81 Relationships between dietary diversity and gut microbial diversity in the elderly. 36377581 10 82 theme gut 1626:1628 arg1 microbiota 1630:1639 the gut microbiota 1622:1639 the gut microbiota 1622:1639 Our results suggest that dietary diversity contributes to the diversity of the gut microbiota and increases the abundance of SCFAs-producing bacteria, but only up to a certain age. 36377581 1 83 theme microbiota 128:137 arg1 composition 139:149 gut microbiota composition 124:149 gut microbiota composition 124:149 Diet is considered as a major driver of gut microbiota composition. 35572716 0 0 theme Sheep 92:96 arg1 Segments 64:71 Different Intestinal Segments 43:71 Different Intestinal Segments of Aohan Fine-Wool Sheep 43:96 Characteristics of Bacterial Microbiota in Different Intestinal Segments of Aohan Fine-Wool Sheep. 35572716 3 1 theme semi-desert 324:334 arg1 grasslands 336:345 semi-desert grasslands 324:345 semi-desert grasslands in China 324:354 Aohan fine-wool sheep grow in semi-desert grasslands in China and show excellent stress tolerance. 35572716 11 2 theme Mongolian 1628:1636 arg1 sheep 1638:1642 Mongolian sheep 1628:1642 Mongolian sheep 1628:1642 Interestingly, these unique bacteria have not been reported in Mongolian sheep or other sheep breeds. 35572716 0 3 theme Fine-Wool 82:90 arg1 Sheep 92:96 Aohan Fine-Wool Sheep 76:96 Aohan Fine-Wool Sheep 76:96 Characteristics of Bacterial Microbiota in Different Intestinal Segments of Aohan Fine-Wool Sheep. 35572716 11 4 theme other 1647:1651 arg1 breeds 1659:1664 other sheep breeds 1647:1664 other sheep breeds 1647:1664 Interestingly, these unique bacteria have not been reported in Mongolian sheep or other sheep breeds. 35572716 7 5 theme dominant 1061:1068 arg1 bacteria 1070:1077 the dominant bacteria 1057:1077 the dominant bacteria 1057:1077 We found that from the foregut to the hindgut, the dominant bacteria changed from Proteobacteria to Bacteroidetes. 35572716 9 6 from hindgut 1343:1349 arg1 abundant 1331:1338 abundant 1331:1338 abundant 1331:1338 Ruminococcaceae and Caldicoprobacteraceae were significantly abundant in hindgut, which can degrade cellulose polysaccharides in the large intestine and produce beneficial metabolites. 35572716 12 7 theme fine-wool 1709:1717 arg1 sheep 1719:1723 Aohan fine-wool sheep 1703:1723 Aohan fine-wool sheep 1703:1723 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 6 8 theme hindgut 949:955 arg1 richness 919:926 bacterial richness 909:926 bacterial richness 909:926 Meanwhile, the diversity index results revealed that the bacterial richness and diversity of the hindgut were significantly higher than those of the foregut. 35572716 6 8 theme hindgut 949:955 arg1 diversity 932:940 diversity 932:940 diversity 932:940 Meanwhile, the diversity index results revealed that the bacterial richness and diversity of the hindgut were significantly higher than those of the foregut. 35572716 3 9 theme excellent 365:373 arg1 tolerance 382:390 excellent stress tolerance 365:390 excellent stress tolerance 365:390 Aohan fine-wool sheep grow in semi-desert grasslands in China and show excellent stress tolerance. 35572716 0 10 from Characteristics 0:14 arg1 Segments 64:71 Different Intestinal Segments 43:71 Different Intestinal Segments of Aohan Fine-Wool Sheep 43:96 Characteristics of Bacterial Microbiota in Different Intestinal Segments of Aohan Fine-Wool Sheep. 35572716 12 11 theme Aohan 1703:1707 arg1 sheep 1719:1723 Aohan fine-wool sheep 1703:1723 Aohan fine-wool sheep 1703:1723 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 6 12 dep index 877:881 arg1 results 883:889 results 883:889 results 883:889 Meanwhile, the diversity index results revealed that the bacterial richness and diversity of the hindgut were significantly higher than those of the foregut. 35572716 3 13 theme stress 375:380 arg1 tolerance 382:390 excellent stress tolerance 365:390 excellent stress tolerance 365:390 Aohan fine-wool sheep grow in semi-desert grasslands in China and show excellent stress tolerance. 35572716 8 14 from bacteria 1200:1207 arg1 foregut 1216:1222 the foregut 1212:1222 the foregut 1212:1222 In LEfSe analysis, Succiniclasticum was found to be significantly abundant bacteria in the foregut and was involved in succinic acid metabolism. 35572716 12 15 theme grassland 1775:1783 arg1 environment 1785:1795 the semi-desert grassland environment 1759:1795 the semi-desert grassland environment 1759:1795 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 13 16 theme microbiota 1852:1861 arg1 role 1840:1843 the role 1836:1843 the role of gut microbiota in improving stress tolerance and gut health in sheep 1836:1915 Our results provide new insights into the role of gut microbiota in improving stress tolerance and gut health in sheep. 35572716 5 17 theme genetic 781:787 arg1 distance 789:796 the genetic distance 777:796 the genetic distance 777:796 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 5 17 theme genetic 781:787 arg1 similar 843:849 similar 843:849 similar 843:849 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 1 18 theme animals 176:182 arg1 system 166:171 the intestinal system 151:171 the intestinal system of animals 151:182 The microbial community performs vital functions in the intestinal system of animals. 35572716 5 19 theme large 702:706 arg1 intestine 708:716 the large intestine 698:716 the large intestine (collectively termed the hindgut) 698:750 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 6 20 dep richness 919:926 arg1 the 905:907 the 905:907 the 905:907 Meanwhile, the diversity index results revealed that the bacterial richness and diversity of the hindgut were significantly higher than those of the foregut. 35572716 4 21 theme gut 499:501 arg1 microbiome 503:512 the gut microbiome 495:512 the gut microbiome 495:512 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 11 22 theme unique 1586:1591 arg1 bacteria 1593:1600 these unique bacteria 1580:1600 these unique bacteria 1580:1600 Interestingly, these unique bacteria have not been reported in Mongolian sheep or other sheep breeds. 35572716 2 23 theme host 277:280 arg1 metabolism 282:291 host metabolism 277:291 host metabolism 277:291 Modulation of the gut microbiota structure can indirectly or directly affect gut health and host metabolism. 35572716 12 24 theme gut 1685:1687 arg1 microbiota 1689:1698 the gut microbiota 1681:1698 the gut microbiota of Aohan fine-wool sheep 1681:1723 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 12 24 theme gut 1685:1687 arg1 one 1728:1730 one 1728:1730 one 1728:1730 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 12 24 theme gut 1685:1687 arg1 keys 1739:1742 the keys 1735:1742 the keys to adapting to the semi-desert grassland environment 1735:1795 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 9 25 from abundant 1331:1338 arg1 hindgut 1343:1349 hindgut 1343:1349 hindgut 1343:1349 Ruminococcaceae and Caldicoprobacteraceae were significantly abundant in hindgut, which can degrade cellulose polysaccharides in the large intestine and produce beneficial metabolites. 35572716 8 26 theme LEfSe 1128:1132 arg1 analysis 1134:1141 LEfSe analysis 1128:1141 LEfSe analysis 1128:1141 In LEfSe analysis, Succiniclasticum was found to be significantly abundant bacteria in the foregut and was involved in succinic acid metabolism. 35572716 4 27 from adaptability 479:490 arg1 rectum 565:570 rectum 565:570 rectum 565:570 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 27 from adaptability 479:490 arg1 ileum 540:544 ileum 540:544 ileum 540:544 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 27 from adaptability 479:490 arg1 cecum 547:551 cecum 547:551 cecum 547:551 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 27 from adaptability 479:490 arg1 duodenum 521:528 duodenum 521:528 duodenum 521:528 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 27 from adaptability 479:490 arg1 jejunum 531:537 jejunum 531:537 jejunum 531:537 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 27 from adaptability 479:490 arg1 colon 554:558 colon 554:558 colon 554:558 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 5 28 theme intestine 708:716 arg1 diversity 671:679 diversity 671:679 diversity 671:679 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 5 28 theme intestine 708:716 arg1 composition 655:665 microbial composition 645:665 microbial composition 645:665 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 5 29 dep termed 732:737 arg1 collectively 719:730 collectively 719:730 collectively 719:730 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 13 30 theme stress 1876:1881 arg1 tolerance 1883:1891 stress tolerance 1876:1891 stress tolerance 1876:1891 Our results provide new insights into the role of gut microbiota in improving stress tolerance and gut health in sheep. 35572716 9 31 theme beneficial 1431:1440 arg1 metabolites 1442:1452 beneficial metabolites 1431:1452 beneficial metabolites 1431:1452 Ruminococcaceae and Caldicoprobacteraceae were significantly abundant in hindgut, which can degrade cellulose polysaccharides in the large intestine and produce beneficial metabolites. 35572716 5 32 dep ileum 688:692 arg1 the 684:686 the 684:686 the 684:686 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 8 33 theme abundant 1191:1198 arg1 bacteria 1200:1207 significantly abundant bacteria 1177:1207 significantly abundant bacteria 1177:1207 In LEfSe analysis, Succiniclasticum was found to be significantly abundant bacteria in the foregut and was involved in succinic acid metabolism. 35572716 4 34 theme rRNA 425:428 arg1 gene 430:433 16S rRNA gene 421:433 16S rRNA gene 421:433 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 0 35 theme Microbiota 29:38 arg1 Characteristics 0:14 Characteristics 0:14 Characteristics of Bacterial Microbiota in Different Intestinal Segments of Aohan Fine-Wool Sheep. 0:97 Characteristics of Bacterial Microbiota in Different Intestinal Segments of Aohan Fine-Wool Sheep. 35572716 4 36 from distribution 462:473 arg1 rectum 565:570 rectum 565:570 rectum 565:570 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 36 from distribution 462:473 arg1 ileum 540:544 ileum 540:544 ileum 540:544 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 36 from distribution 462:473 arg1 cecum 547:551 cecum 547:551 cecum 547:551 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 36 from distribution 462:473 arg1 duodenum 521:528 duodenum 521:528 duodenum 521:528 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 36 from distribution 462:473 arg1 jejunum 531:537 jejunum 531:537 jejunum 531:537 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 36 from distribution 462:473 arg1 colon 554:558 colon 554:558 colon 554:558 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 12 37 theme semi-desert 1763:1773 arg1 environment 1785:1795 the semi-desert grassland environment 1759:1795 the semi-desert grassland environment 1759:1795 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 1 38 theme microbial 103:111 arg1 community 113:121 The microbial community 99:121 The microbial community 99:121 The microbial community performs vital functions in the intestinal system of animals. 35572716 0 39 theme Bacterial 19:27 arg1 Microbiota 29:38 Bacterial Microbiota 19:38 Bacterial Microbiota 19:38 Characteristics of Bacterial Microbiota in Different Intestinal Segments of Aohan Fine-Wool Sheep. 35572716 3 40 theme Aohan 294:298 arg1 sheep 310:314 Aohan fine-wool sheep 294:314 Aohan fine-wool sheep 294:314 Aohan fine-wool sheep grow in semi-desert grasslands in China and show excellent stress tolerance. 35572716 13 41 theme new 1818:1820 arg1 insights 1822:1829 new insights 1818:1829 new insights into the role of gut microbiota in improving stress tolerance and gut health in sheep 1818:1915 Our results provide new insights into the role of gut microbiota in improving stress tolerance and gut health in sheep. 35572716 12 42 theme keys 1739:1742 arg1 microbiota 1689:1698 the gut microbiota 1681:1698 the gut microbiota of Aohan fine-wool sheep 1681:1723 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 12 42 theme keys 1739:1742 arg1 one 1728:1730 one 1728:1730 one 1728:1730 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 12 42 theme keys 1739:1742 arg1 keys 1739:1742 the keys 1735:1742 the keys to adapting to the semi-desert grassland environment 1735:1795 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 6 43 theme diversity 867:875 arg1 Meanwhile 852:860 Meanwhile 852:860 Meanwhile 852:860 Meanwhile, the diversity index results revealed that the bacterial richness and diversity of the hindgut were significantly higher than those of the foregut. 35572716 6 43 theme diversity 867:875 arg1 index 877:881 the diversity index 863:881 the diversity index results 863:889 Meanwhile, the diversity index results revealed that the bacterial richness and diversity of the hindgut were significantly higher than those of the foregut. 35572716 4 44 theme sheep 597:601 arg1 rectum 565:570 rectum 565:570 rectum 565:570 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 44 theme sheep 597:601 arg1 ileum 540:544 ileum 540:544 ileum 540:544 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 44 theme sheep 597:601 arg1 cecum 547:551 cecum 547:551 cecum 547:551 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 44 theme sheep 597:601 arg1 duodenum 521:528 duodenum 521:528 duodenum 521:528 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 44 theme sheep 597:601 arg1 jejunum 531:537 jejunum 531:537 jejunum 531:537 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 44 theme sheep 597:601 arg1 colon 554:558 colon 554:558 colon 554:558 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 0 45 theme Different 43:51 arg1 Segments 64:71 Different Intestinal Segments 43:71 Different Intestinal Segments of Aohan Fine-Wool Sheep 43:96 Characteristics of Bacterial Microbiota in Different Intestinal Segments of Aohan Fine-Wool Sheep. 35572716 6 46 theme bacterial 909:917 arg1 richness 919:926 bacterial richness 909:926 bacterial richness 909:926 Meanwhile, the diversity index results revealed that the bacterial richness and diversity of the hindgut were significantly higher than those of the foregut. 35572716 5 47 dep intestine 708:716 arg1 termed 732:737 termed 732:737 termed the hindgut 732:749 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 13 48 theme gut 1897:1899 arg1 health 1901:1906 gut health 1897:1906 gut health 1897:1906 Our results provide new insights into the role of gut microbiota in improving stress tolerance and gut health in sheep. 35572716 13 49 theme gut 1848:1850 arg1 microbiota 1852:1861 gut microbiota 1848:1861 gut microbiota 1848:1861 Our results provide new insights into the role of gut microbiota in improving stress tolerance and gut health in sheep. 35572716 5 50 theme functional 802:811 arg1 projections 813:823 functional projections 802:823 functional projections 802:823 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 4 51 theme 16S 421:423 arg1 rRNA 425:428 16S rRNA 421:428 16S rRNA gene 421:433 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 11 52 theme sheep 1653:1657 arg1 breeds 1659:1664 other sheep breeds 1647:1664 other sheep breeds 1647:1664 Interestingly, these unique bacteria have not been reported in Mongolian sheep or other sheep breeds. 35572716 9 53 theme cellulose 1370:1378 arg1 polysaccharides 1380:1394 cellulose polysaccharides 1370:1394 cellulose polysaccharides in the large intestine 1370:1417 Ruminococcaceae and Caldicoprobacteraceae were significantly abundant in hindgut, which can degrade cellulose polysaccharides in the large intestine and produce beneficial metabolites. 35572716 5 54 theme ileum 688:692 arg1 diversity 671:679 diversity 671:679 diversity 671:679 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 5 54 theme ileum 688:692 arg1 composition 655:665 microbial composition 645:665 microbial composition 645:665 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 4 55 theme dynamic 454:460 arg1 distribution 462:473 the dynamic distribution 450:473 the dynamic distribution 450:473 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 5 56 theme microbial 645:653 arg1 composition 655:665 microbial composition 645:665 microbial composition 645:665 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 0 57 theme Intestinal 53:62 arg1 Segments 64:71 Different Intestinal Segments 43:71 Different Intestinal Segments of Aohan Fine-Wool Sheep 43:96 Characteristics of Bacterial Microbiota in Different Intestinal Segments of Aohan Fine-Wool Sheep. 35572716 9 58 from polysaccharides 1380:1394 arg1 intestine 1409:1417 the large intestine 1399:1417 the large intestine 1399:1417 Ruminococcaceae and Caldicoprobacteraceae were significantly abundant in hindgut, which can degrade cellulose polysaccharides in the large intestine and produce beneficial metabolites. 35572716 2 59 theme structure 218:226 arg1 Modulation 185:194 Modulation 185:194 Modulation of the gut microbiota structure 185:226 Modulation of the gut microbiota structure can indirectly or directly affect gut health and host metabolism. 35572716 3 60 from grasslands 336:345 arg1 China 350:354 China 350:354 China 350:354 Aohan fine-wool sheep grow in semi-desert grasslands in China and show excellent stress tolerance. 35572716 1 61 theme vital 132:136 arg1 functions 138:146 vital functions 132:146 vital functions 132:146 The microbial community performs vital functions in the intestinal system of animals. 35572716 3 62 theme fine-wool 300:308 arg1 sheep 310:314 Aohan fine-wool sheep 294:314 Aohan fine-wool sheep 294:314 Aohan fine-wool sheep grow in semi-desert grasslands in China and show excellent stress tolerance. 35572716 2 63 theme microbiota 207:216 arg1 structure 218:226 the gut microbiota structure 199:226 the gut microbiota structure 199:226 Modulation of the gut microbiota structure can indirectly or directly affect gut health and host metabolism. 35572716 5 64 dep composition 655:665 arg1 the 641:643 the 641:643 the 641:643 The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. 35572716 12 65 theme sheep 1719:1723 arg1 microbiota 1689:1698 the gut microbiota 1681:1698 the gut microbiota of Aohan fine-wool sheep 1681:1723 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 12 65 theme sheep 1719:1723 arg1 one 1728:1730 one 1728:1730 one 1728:1730 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 12 65 theme sheep 1719:1723 arg1 keys 1739:1742 the keys 1735:1742 the keys to adapting to the semi-desert grassland environment 1735:1795 Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. 35572716 2 66 theme gut 203:205 arg1 structure 218:226 the gut microbiota structure 199:226 the gut microbiota structure 199:226 Modulation of the gut microbiota structure can indirectly or directly affect gut health and host metabolism. 35572716 8 67 located found 1165:1169 arg2 Succiniclasticum 1144:1159 Succiniclasticum 1144:1159 Succiniclasticum 1144:1159 In LEfSe analysis, Succiniclasticum was found to be significantly abundant bacteria in the foregut and was involved in succinic acid metabolism. 35572716 8 67 located found 1165:1169 arg1 analysis 1134:1141 LEfSe analysis 1128:1141 LEfSe analysis 1128:1141 In LEfSe analysis, Succiniclasticum was found to be significantly abundant bacteria in the foregut and was involved in succinic acid metabolism. 35572716 8 68 theme succinic 1244:1251 arg1 metabolism 1258:1267 succinic acid metabolism 1244:1267 succinic acid metabolism 1244:1267 In LEfSe analysis, Succiniclasticum was found to be significantly abundant bacteria in the foregut and was involved in succinic acid metabolism. 35572716 8 69 theme acid 1253:1256 arg1 metabolism 1258:1267 succinic acid metabolism 1244:1267 succinic acid metabolism 1244:1267 In LEfSe analysis, Succiniclasticum was found to be significantly abundant bacteria in the foregut and was involved in succinic acid metabolism. 35572716 0 70 theme Aohan 76:80 arg1 Sheep 92:96 Aohan Fine-Wool Sheep 76:96 Aohan Fine-Wool Sheep 76:96 Characteristics of Bacterial Microbiota in Different Intestinal Segments of Aohan Fine-Wool Sheep. 35572716 2 71 theme gut 262:264 arg1 health 266:271 gut health 262:271 gut health 262:271 Modulation of the gut microbiota structure can indirectly or directly affect gut health and host metabolism. 35572716 10 72 theme flavonoid 1517:1525 arg1 metabolism 1527:1536 flavonoid metabolism 1517:1536 flavonoid metabolism 1517:1536 Moreover, Coriobacteriaceae and Eggthellaceae are involved in flavonoid metabolism and polyphenol production. 35572716 10 73 theme polyphenol 1542:1551 arg1 production 1553:1562 polyphenol production 1542:1562 polyphenol production 1542:1562 Moreover, Coriobacteriaceae and Eggthellaceae are involved in flavonoid metabolism and polyphenol production. 35572716 4 74 theme fine-wool 587:595 arg1 sheep 597:601 seven Aohan fine-wool sheep 575:601 seven Aohan fine-wool sheep 575:601 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 9 75 theme large 1403:1407 arg1 intestine 1409:1417 the large intestine 1399:1417 the large intestine 1399:1417 Ruminococcaceae and Caldicoprobacteraceae were significantly abundant in hindgut, which can degrade cellulose polysaccharides in the large intestine and produce beneficial metabolites. 35572716 4 76 theme microbiome 503:512 arg1 adaptability 479:490 adaptability 479:490 adaptability 479:490 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 4 76 theme microbiome 503:512 arg1 distribution 462:473 the dynamic distribution 450:473 the dynamic distribution 450:473 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35572716 1 77 theme intestinal 155:164 arg1 system 166:171 the intestinal system 151:171 the intestinal system of animals 151:182 The microbial community performs vital functions in the intestinal system of animals. 35572716 4 78 theme Aohan 581:585 arg1 sheep 597:601 seven Aohan fine-wool sheep 575:601 seven Aohan fine-wool sheep 575:601 In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. 35263369 5 0 theme Amide 803:807 arg1 ratio 820:824 Amide I/Amide II ratio 803:824 Amide I/Amide II ratio 803:824 Amide I/Amide II ratio decrease before and increase after chemotherapy, whereas DNA, RNA, and glycogen contents increase before and decrease after the treatment. 35263369 2 1 theme detailed 352:359 arg1 composition 373:383 the detailed biochemical composition 348:383 the detailed biochemical composition of TNBC 348:391 The insight into the detailed biochemical composition of TNBC would help develop dedicated treatments. 35263369 0 2 theme vibrational 84:94 arg1 spectroscopy 96:107 vibrational spectroscopy 84:107 vibrational spectroscopy 84:107 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 35263369 3 3 theme absorbance 530:539 arg1 ratios 541:546 absorbance ratios 530:546 absorbance ratios 530:546 Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. 35263369 6 4 theme response 1044:1051 arg1 scheme 1053:1058 a clinical response scheme 1033:1058 a clinical response scheme 1033:1058 The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible. 35263369 0 5 theme chemometric 113:123 arg1 approach 125:132 chemometric approach 113:132 chemometric approach 113:132 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 35263369 6 6 dep spectroscopy 1122:1133 arg1 possible 1138:1145 possible 1138:1145 possible 1138:1145 The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible. 35263369 6 7 theme clinical 1035:1042 arg1 scheme 1053:1058 a clinical response scheme 1033:1058 a clinical response scheme 1033:1058 The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible. 35263369 1 8 theme targeted 268:275 arg1 therapies 277:285 targeted therapies 268:285 targeted therapies 268:285 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 4 9 theme primary 679:685 arg1 differences 696:706 The primary spectral differences 675:706 The primary spectral differences between control and cancer tissues 675:741 The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. 35263369 5 10 dep decrease 826:833 arg1 whereas 875:881 whereas 875:881 whereas 875:881 Amide I/Amide II ratio decrease before and increase after chemotherapy, whereas DNA, RNA, and glycogen contents increase before and decrease after the treatment. 35263369 1 11 with patients 306:313 arg1 recurrent 320:328 recurrent 320:328 recurrent 320:328 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 3 12 dep chemometrics 513:524 arg1 investigation 548:560 investigation 548:560 investigation 548:560 Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. 35263369 4 13 theme spectral 687:694 arg1 differences 696:706 The primary spectral differences 675:706 The primary spectral differences between control and cancer tissues 675:741 The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. 35263369 5 14 theme I/Amide 809:815 arg1 ratio 820:824 Amide I/Amide II ratio 803:824 Amide I/Amide II ratio 803:824 Amide I/Amide II ratio decrease before and increase after chemotherapy, whereas DNA, RNA, and glycogen contents increase before and decrease after the treatment. 35263369 2 15 theme TNBC 388:391 arg1 composition 373:383 the detailed biochemical composition 348:383 the detailed biochemical composition of TNBC 348:391 The insight into the detailed biochemical composition of TNBC would help develop dedicated treatments. 35263369 3 16 with controls 594:601 arg1 tissue 613:618 TNBC tissue 608:618 TNBC tissue 608:618 Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. 35263369 1 17 theme therapies 277:285 arg1 lack 260:263 lack 260:263 lack of targeted therapies 260:285 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 17 theme therapies 277:285 arg1 survival 247:254 poor overall survival 234:254 poor overall survival 234:254 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 3 18 theme TNBC 608:611 arg1 tissue 613:618 TNBC tissue 608:618 TNBC tissue 608:618 Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. 35263369 5 19 theme glycogen 897:904 arg1 contents 906:913 glycogen contents 897:913 glycogen contents 897:913 Amide I/Amide II ratio decrease before and increase after chemotherapy, whereas DNA, RNA, and glycogen contents increase before and decrease after the treatment. 35263369 0 20 theme cancer 27:32 arg1 Characterisation 0:15 Characterisation 0:15 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 0:133 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 35263369 3 21 theme healthy 586:592 arg1 controls 594:601 healthy controls 586:601 healthy controls with TNBC tissue 586:618 Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. 35263369 1 22 theme aggressive 196:205 arg1 cancer 158:163 Triple negative breast cancer 135:163 Triple negative breast cancer (TNBC) 135:170 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 22 theme aggressive 196:205 arg1 subtype 221:227 the most aggressive breast cancer subtype 187:227 the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies 187:285 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 0 23 theme breast 20:25 arg1 cancer 27:32 breast cancer molecular signature and treatment assessment 20:77 cancer 27:32 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 35263369 6 24 theme discriminatory 998:1011 arg1 features 1013:1020 discriminatory features 998:1020 discriminatory features reflecting a clinical response scheme 998:1058 The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible. 35263369 1 25 with subtype 221:227 arg1 lack 260:263 lack 260:263 lack of targeted therapies 260:285 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 25 with subtype 221:227 arg1 survival 247:254 poor overall survival 234:254 poor overall survival 234:254 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 26 theme breast 207:212 arg1 cancer 158:163 Triple negative breast cancer 135:163 Triple negative breast cancer (TNBC) 135:170 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 26 theme breast 207:212 arg1 subtype 221:227 the most aggressive breast cancer subtype 187:227 the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies 187:285 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 2 27 theme dedicated 412:420 arg1 treatments 422:431 dedicated treatments 412:431 dedicated treatments 412:431 The insight into the detailed biochemical composition of TNBC would help develop dedicated treatments. 35263369 1 28 theme cancer 214:219 arg1 cancer 158:163 Triple negative breast cancer 135:163 Triple negative breast cancer (TNBC) 135:170 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 28 theme cancer 214:219 arg1 subtype 221:227 the most aggressive breast cancer subtype 187:227 the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies 187:285 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 0 29 theme molecular 34:42 arg1 signature 44:52 molecular signature 34:52 molecular signature 34:52 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 35263369 1 30 theme many 301:304 arg1 patients 306:313 many patients 301:313 many patients with recurrent 301:328 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 6 31 theme efficacy 1088:1095 arg1 assessment 1097:1106 the chemotherapy efficacy assessment 1071:1106 the chemotherapy efficacy assessment 1071:1106 The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible. 35263369 0 32 theme treatment 58:66 arg1 assessment 68:77 treatment assessment 58:77 treatment assessment 58:77 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 35263369 6 33 theme chemometric 969:979 arg1 results 981:987 The chemometric results 965:987 The chemometric results 965:987 The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible. 35263369 1 34 theme Triple 135:140 arg1 TNBC 166:169 TNBC 166:169 TNBC 166:169 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 34 theme Triple 135:140 arg1 cancer 158:163 Triple negative breast cancer 135:163 Triple negative breast cancer (TNBC) 135:170 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 34 theme Triple 135:140 arg1 subtype 221:227 the most aggressive breast cancer subtype 187:227 the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies 187:285 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 35 theme negative 142:149 arg1 TNBC 166:169 TNBC 166:169 TNBC 166:169 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 35 theme negative 142:149 arg1 cancer 158:163 Triple negative breast cancer 135:163 Triple negative breast cancer (TNBC) 135:170 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 35 theme negative 142:149 arg1 subtype 221:227 the most aggressive breast cancer subtype 187:227 the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies 187:285 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 4 36 dep control 716:722 arg1 tissues 735:741 tissues 735:741 tissues 735:741 The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. 35263369 0 37 dep cancer 27:32 arg1 signature 44:52 molecular signature 34:52 molecular signature 34:52 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 35263369 0 38 with Characterisation 0:15 arg1 spectroscopy 96:107 vibrational spectroscopy 84:107 vibrational spectroscopy 84:107 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 35263369 0 38 with Characterisation 0:15 arg1 approach 125:132 chemometric approach 113:132 chemometric approach 113:132 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 35263369 1 39 theme breast 151:156 arg1 TNBC 166:169 TNBC 166:169 TNBC 166:169 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 39 theme breast 151:156 arg1 cancer 158:163 Triple negative breast cancer 135:163 Triple negative breast cancer (TNBC) 135:170 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 1 39 theme breast 151:156 arg1 subtype 221:227 the most aggressive breast cancer subtype 187:227 the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies 187:285 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 4 40 theme nucleic 788:794 arg1 acids 796:800 nucleic acids 788:800 nucleic acids 788:800 The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. 35263369 6 41 theme chemotherapy 1075:1086 arg1 assessment 1097:1106 the chemotherapy efficacy assessment 1071:1106 the chemotherapy efficacy assessment 1071:1106 The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible. 35263369 3 42 theme same 661:664 arg1 patient 666:672 the same patient 657:672 the same patient 657:672 Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. 35263369 1 43 theme poor 234:237 arg1 survival 247:254 poor overall survival 234:254 poor overall survival 234:254 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 6 44 theme infrared 1113:1120 arg1 spectroscopy 1122:1133 infrared spectroscopy 1113:1133 infrared spectroscopy is possible 1113:1145 The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible. 35263369 1 45 theme overall 239:245 arg1 survival 247:254 poor overall survival 234:254 poor overall survival 234:254 Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. 35263369 0 46 theme assessment 68:77 arg1 Characterisation 0:15 Characterisation 0:15 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 0:133 Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach. 35263369 4 47 located found 748:752 arg2 differences 696:706 The primary spectral differences 675:706 The primary spectral differences between control and cancer tissues 675:741 The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. 35263369 4 47 located found 748:752 arg1 proteins 757:764 proteins 757:764 proteins 757:764 The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. 35263369 4 47 located found 748:752 arg1 polysaccharides 767:781 polysaccharides 767:781 polysaccharides 767:781 The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. 35263369 4 47 located found 748:752 arg1 acids 796:800 nucleic acids 788:800 nucleic acids 788:800 The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. 35263369 2 48 theme biochemical 361:371 arg1 composition 373:383 the detailed biochemical composition 348:383 the detailed biochemical composition of TNBC 348:391 The insight into the detailed biochemical composition of TNBC would help develop dedicated treatments. 37151667 11 0 theme hemocyte 2234:2241 arg1 specification 2243:2255 bivalve's hemocyte specification 2224:2255 bivalve's hemocyte specification 2224:2255 Our results support a concept of bivalve's hemocyte specification with distinct phenotypes. 37151667 6 1 theme smooth 1152:1157 arg1 apparatus 1130:1138 a well-developed protein-synthesizing apparatus 1092:1138 a well-developed protein-synthesizing apparatus 1092:1138 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 1 theme smooth 1152:1157 arg1 reticulum 1171:1179 smooth endoplasmic reticulum 1152:1179 smooth endoplasmic reticulum 1152:1179 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 2 2 theme adaptive 322:329 arg1 mechanisms 346:355 the adaptive and protective mechanisms 318:355 the adaptive and protective mechanisms of bivalves 318:367 Even though hemocytes are known to play a key role in the adaptive and protective mechanisms of bivalves, these cells are poorly studied in horse-mussel Modiolus kurilensis. 37151667 8 3 theme anticancer 1776:1785 arg1 activity 1787:1794 pronounced antibacterial and anticancer activity 1747:1794 pronounced antibacterial and anticancer activity 1747:1794 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 1 4 theme marine 244:249 arg1 environment 251:261 the marine environment 240:261 the marine environment 240:261 Bivalves, such as Modiolus are used as indicator organisms to monitor the state of the marine environment. 37151667 7 5 theme phagocytic 1552:1561 arg1 activities 1563:1572 phagocytic activities 1552:1572 phagocytic activities 1552:1572 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 11 6 theme bivalve 2224:2230 arg1 specification 2243:2255 bivalve's hemocyte specification 2224:2255 bivalve's hemocyte specification 2224:2255 Our results support a concept of bivalve's hemocyte specification with distinct phenotypes. 37151667 7 7 theme reactive 1518:1525 arg1 ROS 1543:1545 ROS 1543:1545 ROS 1543:1545 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 7 7 theme reactive 1518:1525 arg1 species 1534:1540 reactive oxygen species 1518:1540 reactive oxygen species (ROS) 1518:1546 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 6 8 theme acidic 1243:1248 arg1 proteins 1250:1257 acidic proteins 1243:1257 acidic proteins 1243:1257 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 5 9 theme bromodeoxyuridine 919:935 arg1 nucleus 946:952 a bromodeoxyuridine positive nucleus 917:952 a bromodeoxyuridine positive nucleus 917:952 First subpopulation consisted of small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus, and did not show any immune reactivity. 37151667 3 10 theme horse-mussel 482:493 arg1 hemocytes 495:503 horse-mussel hemocytes 482:503 horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation 482:693 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 1 11 theme indicator 196:204 arg1 Bivalves 157:164 Bivalves 157:164 Bivalves 157:164 Bivalves, such as Modiolus are used as indicator organisms to monitor the state of the marine environment. 37151667 1 11 theme indicator 196:204 arg1 organisms 206:214 indicator organisms 196:214 indicator organisms 196:214 Bivalves, such as Modiolus are used as indicator organisms to monitor the state of the marine environment. 37151667 1 11 theme indicator 196:204 arg1 Modiolus 175:182 Modiolus 175:182 Modiolus 175:182 Bivalves, such as Modiolus are used as indicator organisms to monitor the state of the marine environment. 37151667 0 12 from production 84:93 arg1 kurilensis 145:154 the bivalve Modiolus kurilensis 124:154 the bivalve Modiolus kurilensis 124:154 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 7 13 theme density 1473:1479 arg1 contents 1451:1458 contents 1451:1458 contents of different density 1451:1479 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 7 14 theme lysosomes 1410:1418 arg1 number 1400:1405 the largest number 1388:1405 the largest number of lysosomes, peroxisomes and vesicles 1388:1444 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 10 15 theme key 2124:2126 arg1 element 2128:2134 the key element 2120:2134 the key element of the cell-mediated immune response of M. kurilensis 2120:2188 Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. 37151667 10 15 theme key 2124:2126 arg1 group 2111:2115 this group 2106:2115 this group 2106:2115 Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. 37151667 0 16 theme Modiolus 136:143 arg1 kurilensis 145:154 the bivalve Modiolus kurilensis 124:154 the bivalve Modiolus kurilensis 124:154 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 3 17 theme molecules 590:598 arg1 production 552:561 the production 548:561 the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation 548:693 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 5 18 theme small 859:863 arg1 hemoblasts 886:895 small under-differentiated hemoblasts 859:895 small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus 859:952 First subpopulation consisted of small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus, and did not show any immune reactivity. 37151667 5 18 theme small 859:863 arg1 % 909:909 2.20 ± 0.85% 898:909 2.20 ± 0.85% 898:909 First subpopulation consisted of small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus, and did not show any immune reactivity. 37151667 3 19 theme specific 566:573 arg1 molecules 590:598 specific immune-related molecules 566:598 specific immune-related molecules 566:598 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 0 20 from MkC1qDC 113:119 arg1 kurilensis 145:154 the bivalve Modiolus kurilensis 124:154 the bivalve Modiolus kurilensis 124:154 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 1 21 used used 188:191 arg2 Bivalves 157:164 Bivalves 157:164 Bivalves 157:164 Bivalves, such as Modiolus are used as indicator organisms to monitor the state of the marine environment. 37151667 1 21 used used 188:191 arg2 organisms 206:214 indicator organisms 196:214 indicator organisms 196:214 Bivalves, such as Modiolus are used as indicator organisms to monitor the state of the marine environment. 37151667 1 21 used used 188:191 arg2 Modiolus 175:182 Modiolus 175:182 Modiolus 175:182 Bivalves, such as Modiolus are used as indicator organisms to monitor the state of the marine environment. 37151667 10 22 theme cell-mediated 2143:2155 arg1 response 2164:2171 the cell-mediated immune response 2139:2171 the cell-mediated immune response of M. kurilensis 2139:2188 Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. 37151667 7 23 theme largest 1392:1398 arg1 number 1400:1405 the largest number 1388:1405 the largest number of lysosomes, peroxisomes and vesicles 1388:1444 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 5 24 theme under-differentiated 865:884 arg1 hemoblasts 886:895 small under-differentiated hemoblasts 859:895 small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus 859:952 First subpopulation consisted of small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus, and did not show any immune reactivity. 37151667 5 24 theme under-differentiated 865:884 arg1 % 909:909 2.20 ± 0.85% 898:909 2.20 ± 0.85% 898:909 First subpopulation consisted of small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus, and did not show any immune reactivity. 37151667 9 25 theme localization 1858:1869 arg1 intracytoplasmic 1826:1841 intracytoplasmic 1826:1841 intracytoplasmic 1826:1841 These cells characterized by intracytoplasmic of the MkC1qDC localization, forming granule-like bodies visualized with specific antibody. 37151667 4 26 theme effective 699:707 arg1 protocol 723:730 An effective fractionation protocol 696:730 An effective fractionation protocol 696:730 An effective fractionation protocol was adapted to separate four hemocyte subpopulations with distinct morphofunctional profiles. 37151667 7 27 theme Third 1298:1302 arg1 subpopulation 1304:1316 Third subpopulation 1298:1316 Third subpopulation 1298:1316 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 8 28 theme fourth 1583:1588 arg1 producers 1647:1655 main producers 1642:1655 main producers 1642:1655 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 8 28 theme fourth 1583:1588 arg1 group 1590:1594 fourth group 1583:1594 fourth group 1583:1594 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 8 28 theme fourth 1583:1588 arg1 granulocytes 1608:1619 basophilic granulocytes 1597:1619 basophilic granulocytes (14.21 ± 0.34%) 1597:1635 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 10 29 theme response 2164:2171 arg1 element 2128:2134 the key element 2120:2134 the key element of the cell-mediated immune response of M. kurilensis 2120:2188 Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. 37151667 10 29 theme response 2164:2171 arg1 group 2111:2115 this group 2106:2115 this group 2106:2115 Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. 37151667 6 30 contain containing 1081:1090 arg2 polysomes 1141:1149 polysomes 1141:1149 polysomes 1141:1149 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 30 contain containing 1081:1090 arg2 mitochondria 1185:1196 mitochondria 1185:1196 mitochondria 1185:1196 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 30 contain containing 1081:1090 arg1 cytoplasm 1071:1079 evenly filled cytoplasm 1057:1079 evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria 1057:1196 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 30 contain containing 1081:1090 arg2 reticulum 1171:1179 smooth endoplasmic reticulum 1152:1179 smooth endoplasmic reticulum 1152:1179 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 30 contain containing 1081:1090 arg2 apparatus 1130:1138 a well-developed protein-synthesizing apparatus 1092:1138 a well-developed protein-synthesizing apparatus 1092:1138 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 4 31 theme morphofunctional 799:814 arg1 profiles 816:823 distinct morphofunctional profiles 790:823 distinct morphofunctional profiles 790:823 An effective fractionation protocol was adapted to separate four hemocyte subpopulations with distinct morphofunctional profiles. 37151667 0 32 theme MkC1qDC 113:119 arg1 production 84:93 the production 80:93 the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis 80:154 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 0 32 theme MkC1qDC 113:119 arg1 activities 65:74 immune-related activities 50:74 immune-related activities 50:74 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 7 33 theme peroxisomes 1421:1431 arg1 number 1400:1405 the largest number 1388:1405 the largest number of lysosomes, peroxisomes and vesicles 1388:1444 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 4 34 theme separate 747:754 arg1 subpopulations 770:783 separate four hemocyte subpopulations 747:783 separate four hemocyte subpopulations with distinct morphofunctional profiles 747:823 An effective fractionation protocol was adapted to separate four hemocyte subpopulations with distinct morphofunctional profiles. 37151667 2 35 theme bivalves 360:367 arg1 mechanisms 346:355 the adaptive and protective mechanisms 318:355 the adaptive and protective mechanisms of bivalves 318:367 Even though hemocytes are known to play a key role in the adaptive and protective mechanisms of bivalves, these cells are poorly studied in horse-mussel Modiolus kurilensis. 37151667 6 36 theme protein-synthesizing 1109:1128 arg1 mitochondria 1185:1196 mitochondria 1185:1196 mitochondria 1185:1196 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 36 theme protein-synthesizing 1109:1128 arg1 apparatus 1130:1138 a well-developed protein-synthesizing apparatus 1092:1138 a well-developed protein-synthesizing apparatus 1092:1138 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 36 theme protein-synthesizing 1109:1128 arg1 reticulum 1171:1179 smooth endoplasmic reticulum 1152:1179 smooth endoplasmic reticulum 1152:1179 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 36 theme protein-synthesizing 1109:1128 arg1 polysomes 1141:1149 polysomes 1141:1149 polysomes 1141:1149 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 4 37 theme hemocyte 761:768 arg1 subpopulations 770:783 separate four hemocyte subpopulations 747:783 separate four hemocyte subpopulations with distinct morphofunctional profiles 747:823 An effective fractionation protocol was adapted to separate four hemocyte subpopulations with distinct morphofunctional profiles. 37151667 0 38 theme hemocyte 17:24 arg1 subpopulations 26:39 hemocyte subpopulations 17:39 hemocyte subpopulations 17:39 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 5 39 with hemoblasts 886:895 arg1 nucleus 946:952 a bromodeoxyuridine positive nucleus 917:952 a bromodeoxyuridine positive nucleus 917:952 First subpopulation consisted of small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus, and did not show any immune reactivity. 37151667 3 40 theme morphological 618:630 arg1 composition 632:642 their morphological composition 612:642 their morphological composition after isolation 612:658 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 0 41 theme immune-related 50:63 arg1 activities 65:74 immune-related activities 50:74 immune-related activities 50:74 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 3 42 theme gradient 671:678 arg1 centrifugation 680:693 density gradient centrifugation 663:693 density gradient centrifugation 663:693 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 8 43 theme lectin-like 1660:1670 arg1 MkC1qDC 1680:1686 lectin-like protein MkC1qDC 1660:1686 lectin-like protein MkC1qDC 1660:1686 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 10 44 theme ROS 2002:2004 arg1 production 2006:2015 ROS production 2002:2015 ROS production 2002:2015 Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. 37151667 3 45 theme hemocytes 495:503 arg1 classification 464:477 classification 464:477 classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation 464:693 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 6 46 theme endoplasmic 1159:1169 arg1 apparatus 1130:1138 a well-developed protein-synthesizing apparatus 1092:1138 a well-developed protein-synthesizing apparatus 1092:1138 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 46 theme endoplasmic 1159:1169 arg1 reticulum 1171:1179 smooth endoplasmic reticulum 1152:1179 smooth endoplasmic reticulum 1152:1179 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 8 47 theme MkC1qDC 1680:1686 arg1 group 1590:1594 fourth group 1583:1594 fourth group 1583:1594 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 8 47 theme MkC1qDC 1680:1686 arg1 producers 1647:1655 main producers 1642:1655 main producers 1642:1655 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 8 48 theme pronounced 1747:1756 arg1 activity 1787:1794 pronounced antibacterial and anticancer activity 1747:1794 pronounced antibacterial and anticancer activity 1747:1794 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 7 49 theme eosinophilic 1331:1342 arg1 granulocytes 1344:1355 eosinophilic granulocytes 1331:1355 eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities 1331:1572 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 7 49 theme eosinophilic 1331:1342 arg1 % 1370:1370 62.64 ± 9.32% 1358:1370 62.64 ± 9.32% 1358:1370 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 3 50 theme immune 520:525 arg1 functions 527:535 their immune functions 514:535 their immune functions 514:535 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 3 50 theme immune 520:525 arg1 production 552:561 the production 548:561 the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation 548:693 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 1 51 theme environment 251:261 arg1 state 231:235 the state 227:235 the state of the marine environment 227:261 Bivalves, such as Modiolus are used as indicator organisms to monitor the state of the marine environment. 37151667 7 52 theme oxygen 1527:1532 arg1 ROS 1543:1545 ROS 1543:1545 ROS 1543:1545 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 7 52 theme oxygen 1527:1532 arg1 species 1534:1540 reactive oxygen species 1518:1540 reactive oxygen species (ROS) 1518:1546 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 10 53 theme eosinophilic 2063:2074 arg1 granulocytes 2076:2087 eosinophilic granulocytes 2063:2087 eosinophilic granulocytes 2063:2087 Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. 37151667 11 54 theme distinct 2262:2269 arg1 phenotypes 2271:2280 distinct phenotypes 2262:2280 distinct phenotypes 2262:2280 Our results support a concept of bivalve's hemocyte specification with distinct phenotypes. 37151667 7 55 theme highest 1497:1503 arg1 phosphatase 1505:1515 phosphatase 1505:1515 phosphatase 1505:1515 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 0 56 theme bivalve 128:134 arg1 kurilensis 145:154 the bivalve Modiolus kurilensis 124:154 the bivalve Modiolus kurilensis 124:154 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 4 57 with subpopulations 770:783 arg1 profiles 816:823 distinct morphofunctional profiles 790:823 distinct morphofunctional profiles 790:823 An effective fractionation protocol was adapted to separate four hemocyte subpopulations with distinct morphofunctional profiles. 37151667 7 58 contain contained 1378:1386 arg1 granulocytes 1344:1355 eosinophilic granulocytes 1331:1355 eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities 1331:1572 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 7 58 contain contained 1378:1386 arg1 % 1370:1370 62.64 ± 9.32% 1358:1370 62.64 ± 9.32% 1358:1370 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 7 58 contain contained 1378:1386 arg2 number 1400:1405 the largest number 1388:1405 the largest number of lysosomes, peroxisomes and vesicles 1388:1444 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 3 59 theme immune-related 575:588 arg1 molecules 590:598 specific immune-related molecules 566:598 specific immune-related molecules 566:598 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 7 60 dep phosphatase 1505:1515 arg1 the 1493:1495 the 1493:1495 the 1493:1495 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 6 61 dep represented 1006:1016 arg1 cytoplasm 1071:1079 evenly filled cytoplasm 1057:1079 evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria 1057:1196 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 61 dep represented 1006:1016 arg1 stained 1214:1220 stained 1214:1220 positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides 1203:1295 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 7 62 theme different 1463:1471 arg1 density 1473:1479 different density 1463:1479 different density 1463:1479 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 4 63 theme fractionation 709:721 arg1 protocol 723:730 An effective fractionation protocol 696:730 An effective fractionation protocol 696:730 An effective fractionation protocol was adapted to separate four hemocyte subpopulations with distinct morphofunctional profiles. 37151667 6 64 theme filled 1064:1069 arg1 cytoplasm 1071:1079 evenly filled cytoplasm 1057:1079 evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria 1057:1196 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 65 theme neutral 1273:1279 arg1 polysaccharides 1281:1295 neutral polysaccharides 1273:1295 neutral polysaccharides 1273:1295 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 5 66 theme positive 937:944 arg1 nucleus 946:952 a bromodeoxyuridine positive nucleus 917:952 a bromodeoxyuridine positive nucleus 917:952 First subpopulation consisted of small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus, and did not show any immune reactivity. 37151667 9 67 theme MkC1qDC 1850:1856 arg1 localization 1858:1869 the MkC1qDC localization 1846:1869 the MkC1qDC localization 1846:1869 These cells characterized by intracytoplasmic of the MkC1qDC localization, forming granule-like bodies visualized with specific antibody. 37151667 7 68 theme vesicles 1437:1444 arg1 number 1400:1405 the largest number 1388:1405 the largest number of lysosomes, peroxisomes and vesicles 1388:1444 Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. 37151667 8 69 theme protein 1672:1678 arg1 MkC1qDC 1680:1686 lectin-like protein MkC1qDC 1660:1686 lectin-like protein MkC1qDC 1660:1686 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 8 70 theme basophilic 1597:1606 arg1 group 1590:1594 fourth group 1583:1594 fourth group 1583:1594 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 8 70 theme basophilic 1597:1606 arg1 granulocytes 1608:1619 basophilic granulocytes 1597:1619 basophilic granulocytes (14.21 ± 0.34%) 1597:1635 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 8 70 theme basophilic 1597:1606 arg1 % 1634:1634 14.21 ± 0.34% 1622:1634 14.21 ± 0.34% 1622:1634 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 0 71 theme agglutinin 102:111 arg1 MkC1qDC 113:119 the agglutinin MkC1qDC 98:119 the agglutinin MkC1qDC in the bivalve Modiolus kurilensis 98:154 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 9 72 theme granule-like 1880:1891 arg1 bodies 1893:1898 granule-like bodies 1880:1898 granule-like bodies visualized with specific antibody 1880:1932 These cells characterized by intracytoplasmic of the MkC1qDC localization, forming granule-like bodies visualized with specific antibody. 37151667 0 73 from activities 65:74 arg1 kurilensis 145:154 the bivalve Modiolus kurilensis 124:154 the bivalve Modiolus kurilensis 124:154 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 10 74 theme immune 2157:2162 arg1 response 2164:2171 the cell-mediated immune response 2139:2171 the cell-mediated immune response of M. kurilensis 2139:2188 Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. 37151667 4 75 theme distinct 790:797 arg1 profiles 816:823 distinct morphofunctional profiles 790:823 distinct morphofunctional profiles 790:823 An effective fractionation protocol was adapted to separate four hemocyte subpopulations with distinct morphofunctional profiles. 37151667 5 76 theme immune 976:981 arg1 reactivity 983:992 any immune reactivity 972:992 any immune reactivity 972:992 First subpopulation consisted of small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus, and did not show any immune reactivity. 37151667 11 77 with concept 2213:2219 arg1 phenotypes 2271:2280 distinct phenotypes 2262:2280 distinct phenotypes 2262:2280 Our results support a concept of bivalve's hemocyte specification with distinct phenotypes. 37151667 9 78 theme specific 1916:1923 arg1 antibody 1925:1932 specific antibody 1916:1932 specific antibody 1916:1932 These cells characterized by intracytoplasmic of the MkC1qDC localization, forming granule-like bodies visualized with specific antibody. 37151667 8 79 dep producers 1647:1655 arg1 characterized 1730:1742 characterized 1730:1742 characterized by pronounced antibacterial and anticancer activity 1730:1794 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 8 79 dep producers 1647:1655 arg1 discovered 1698:1707 discovered 1698:1707 recently discovered in M. kurilensis 1689:1724 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 0 80 theme subpopulations 26:39 arg1 Specification 0:12 Specification 0:12 Specification of hemocyte subpopulations 0:39 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 6 81 theme well-developed 1094:1107 arg1 mitochondria 1185:1196 mitochondria 1185:1196 mitochondria 1185:1196 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 81 theme well-developed 1094:1107 arg1 apparatus 1130:1138 a well-developed protein-synthesizing apparatus 1092:1138 a well-developed protein-synthesizing apparatus 1092:1138 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 81 theme well-developed 1094:1107 arg1 reticulum 1171:1179 smooth endoplasmic reticulum 1152:1179 smooth endoplasmic reticulum 1152:1179 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 6 81 theme well-developed 1094:1107 arg1 polysomes 1141:1149 polysomes 1141:1149 polysomes 1141:1149 Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. 37151667 3 82 theme composition 632:642 arg1 production 552:561 the production 548:561 the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation 548:693 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 8 83 theme main 1642:1645 arg1 group 1590:1594 fourth group 1583:1594 fourth group 1583:1594 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 8 83 theme main 1642:1645 arg1 producers 1647:1655 main producers 1642:1655 main producers 1642:1655 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 37151667 10 84 theme phagocytic 1978:1987 arg1 activity 1989:1996 phagocytic activity 1978:1996 phagocytic activity 1978:1996 Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. 37151667 5 85 theme First 826:830 arg1 subpopulation 832:844 First subpopulation 826:844 First subpopulation 826:844 First subpopulation consisted of small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus, and did not show any immune reactivity. 37151667 3 86 theme density 663:669 arg1 centrifugation 680:693 density gradient centrifugation 663:693 density gradient centrifugation 663:693 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 0 87 from kurilensis 145:154 arg1 production 84:93 the production 80:93 the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis 80:154 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 0 87 from kurilensis 145:154 arg1 activities 65:74 immune-related activities 50:74 immune-related activities 50:74 Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis. 37151667 2 88 theme key 306:308 arg1 role 310:313 a key role 304:313 a key role 304:313 Even though hemocytes are known to play a key role in the adaptive and protective mechanisms of bivalves, these cells are poorly studied in horse-mussel Modiolus kurilensis. 37151667 3 89 attach present 456:462 arg2 we 453:454 we 453:454 we 453:454 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 3 89 attach present 456:462 arg1 paper 446:450 this paper 441:450 this paper 441:450 In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. 37151667 10 90 theme kurilensis 2179:2188 arg1 response 2164:2171 the cell-mediated immune response 2139:2171 the cell-mediated immune response of M. kurilensis 2139:2188 Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. 37151667 2 91 theme protective 335:344 arg1 mechanisms 346:355 the adaptive and protective mechanisms 318:355 the adaptive and protective mechanisms of bivalves 318:367 Even though hemocytes are known to play a key role in the adaptive and protective mechanisms of bivalves, these cells are poorly studied in horse-mussel Modiolus kurilensis. 37151667 8 92 theme antibacterial 1758:1770 arg1 activity 1787:1794 pronounced antibacterial and anticancer activity 1747:1794 pronounced antibacterial and anticancer activity 1747:1794 Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. 36493475 2 0 theme hydrolysis 579:588 arg1 sample 600:605 The Aspergillus niger-enzyme hydrolysis treatment sample 550:605 The Aspergillus niger-enzyme hydrolysis treatment sample 550:605 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 1 1 theme treatment 398:406 arg1 effects 186:192 The effects 182:192 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues 182:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 2 from effects 186:192 arg1 properties 422:431 structural properties 411:431 structural properties 411:431 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 2 from effects 186:192 arg1 capacities 448:457 adsorption capacities 437:457 adsorption capacities 437:457 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 3 from residues 512:519 arg1 fiber 478:482 soluble dietary fiber 462:482 soluble dietary fiber from Mesona chinensis Benth residues 462:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 3 from residues 512:519 arg1 properties 422:431 structural properties 411:431 structural properties 411:431 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 3 from residues 512:519 arg1 capacities 448:457 adsorption capacities 437:457 adsorption capacities 437:457 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 4 4 theme Aspergillus 878:888 arg1 sample 919:924 The Aspergillus niger fermentation treatment sample 874:924 The Aspergillus niger fermentation treatment sample 874:924 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 2 5 theme niger-enzyme 566:577 arg1 sample 600:605 The Aspergillus niger-enzyme hydrolysis treatment sample 550:605 The Aspergillus niger-enzyme hydrolysis treatment sample 550:605 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 5 6 theme diverse 1203:1209 arg1 methods 1222:1228 diverse extraction methods 1203:1228 diverse extraction methods 1203:1228 Additionally, different monosaccharide composition was exhibited due to diverse extraction methods. 36493475 3 7 theme highest 744:750 arg1 yield 774:778 soluble dietary fiber yield 752:778 the highest soluble dietary fiber yield (20.76 ± 0.31 %) 740:795 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 3 7 theme highest 744:750 arg1 % 794:794 20.76 ± 0.31 % 781:794 20.76 ± 0.31 % 781:794 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 1 8 theme reesei 280:285 arg1 treatment 300:308 Trichoderma reesei fermentation treatment 268:308 Trichoderma reesei fermentation treatment 268:308 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 4 9 theme sodium 1075:1080 arg1 cholate 1082:1088 sodium cholate 1075:1088 sodium cholate adsorption capacity (94.80 ± 1.41 mg/g) 1075:1128 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 1 10 theme structural 411:420 arg1 properties 422:431 structural properties 411:431 structural properties 411:431 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 6 11 theme Benth 1353:1357 arg1 residues 1359:1366 Mesona chinensis Benth residues 1336:1366 Mesona chinensis Benth residues 1336:1366 Our finding revealed that these two modification methods could effectively enhance the economic value of Mesona chinensis Benth residues. 36493475 1 12 theme fermentation 287:298 arg1 treatment 300:308 Trichoderma reesei fermentation treatment 268:308 Trichoderma reesei fermentation treatment 268:308 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 2 13 theme diverse 622:628 arg1 structure 630:638 more diverse structure 617:638 more diverse structure 617:638 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 3 14 theme glucose 825:831 arg1 38.03 ± 0.28 mg/g 854:870 38.03 ± 0.28 mg/g 854:870 38.03 ± 0.28 mg/g 854:870 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 3 14 theme glucose 825:831 arg1 capacity 844:851 glucose adsorption capacity 825:851 glucose adsorption capacity (38.03 ± 0.28 mg/g) 825:871 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 2 15 theme modified 694:701 arg1 samples 703:709 other modified samples 688:709 other modified samples 688:709 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 6 16 theme chinensis 1343:1351 arg1 residues 1359:1366 Mesona chinensis Benth residues 1336:1366 Mesona chinensis Benth residues 1336:1366 Our finding revealed that these two modification methods could effectively enhance the economic value of Mesona chinensis Benth residues. 36493475 1 17 theme treatment 300:308 arg1 effects 186:192 The effects 182:192 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues 182:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 4 18 theme adsorption 1090:1099 arg1 94.80 ± 1.41 mg/g 1111:1127 94.80 ± 1.41 mg/g 1111:1127 94.80 ± 1.41 mg/g 1111:1127 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 4 18 theme adsorption 1090:1099 arg1 capacity 1101:1108 sodium cholate adsorption capacity 1075:1108 sodium cholate adsorption capacity (94.80 ± 1.41 mg/g) 1075:1128 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 3 19 theme adsorption 833:842 arg1 38.03 ± 0.28 mg/g 854:870 38.03 ± 0.28 mg/g 854:870 38.03 ± 0.28 mg/g 854:870 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 3 19 theme adsorption 833:842 arg1 capacity 844:851 glucose adsorption capacity 825:851 glucose adsorption capacity (38.03 ± 0.28 mg/g) 825:871 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 4 20 theme nitrite 965:971 arg1 capacity 988:995 nitrite ion adsorption capacity 965:995 nitrite ion adsorption capacity (181.84 ± 6.67 ug/g) 965:1016 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 4 20 theme nitrite 965:971 arg1 ug/g 1012:1015 181.84 ± 6.67 ug/g 998:1015 181.84 ± 6.67 ug/g 998:1015 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 6 21 theme Mesona 1336:1341 arg1 residues 1359:1366 Mesona chinensis Benth residues 1336:1366 Mesona chinensis Benth residues 1336:1366 Our finding revealed that these two modification methods could effectively enhance the economic value of Mesona chinensis Benth residues. 36493475 0 22 theme cellulase 109:117 arg1 treatment 119:127 cellulase treatment assisted 109:136 cellulase treatment assisted by Aspergillus niger or Trichoderma reesei 109:179 Structural properties and adsorption capacities of Mesona chinensis Benth residues dietary fiber prepared by cellulase treatment assisted by Aspergillus niger or Trichoderma reesei. 36493475 1 23 theme adsorption 437:446 arg1 capacities 448:457 adsorption capacities 437:457 adsorption capacities 437:457 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 24 from capacities 448:457 arg1 residues 512:519 Mesona chinensis Benth residues 489:519 Mesona chinensis Benth residues 489:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 4 25 theme fermentation 896:907 arg1 sample 919:924 The Aspergillus niger fermentation treatment sample 874:924 The Aspergillus niger fermentation treatment sample 874:924 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 3 26 theme dietary 760:766 arg1 yield 774:778 soluble dietary fiber yield 752:778 the highest soluble dietary fiber yield (20.76 ± 0.31 %) 740:795 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 3 26 theme dietary 760:766 arg1 % 794:794 20.76 ± 0.31 % 781:794 20.76 ± 0.31 % 781:794 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 4 27 theme cholesterol 1019:1029 arg1 16.40 ± 0.37 mg/g 1052:1068 16.40 ± 0.37 mg/g 1052:1068 16.40 ± 0.37 mg/g 1052:1068 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 4 27 theme cholesterol 1019:1029 arg1 capacity 1042:1049 cholesterol adsorption capacity 1019:1049 cholesterol adsorption capacity (16.40 ± 0.37 mg/g) 1019:1069 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 4 28 theme adsorption 977:986 arg1 capacity 988:995 nitrite ion adsorption capacity 965:995 nitrite ion adsorption capacity (181.84 ± 6.67 ug/g) 965:1016 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 4 28 theme adsorption 977:986 arg1 ug/g 1012:1015 181.84 ± 6.67 ug/g 998:1015 181.84 ± 6.67 ug/g 998:1015 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 4 29 dep Aspergillus 878:888 arg1 niger 890:894 niger 890:894 niger 890:894 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 0 30 theme Structural 0:9 arg1 properties 11:20 Structural properties 0:20 Structural properties 0:20 Structural properties and adsorption capacities of Mesona chinensis Benth residues dietary fiber prepared by cellulase treatment assisted by Aspergillus niger or Trichoderma reesei. 36493475 4 31 theme ion 973:975 arg1 capacity 988:995 nitrite ion adsorption capacity 965:995 nitrite ion adsorption capacity (181.84 ± 6.67 ug/g) 965:1016 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 4 31 theme ion 973:975 arg1 ug/g 1012:1015 181.84 ± 6.67 ug/g 998:1015 181.84 ± 6.67 ug/g 998:1015 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 6 32 theme economic 1318:1325 arg1 value 1327:1331 the economic value 1314:1331 the economic value of Mesona chinensis Benth residues 1314:1366 Our finding revealed that these two modification methods could effectively enhance the economic value of Mesona chinensis Benth residues. 36493475 1 33 theme enzyme 197:202 arg1 treatment 215:223 enzyme hydrolysis treatment 197:223 enzyme hydrolysis treatment 197:223 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 0 34 theme adsorption 26:35 arg1 capacities 37:46 adsorption capacities 26:46 adsorption capacities 26:46 Structural properties and adsorption capacities of Mesona chinensis Benth residues dietary fiber prepared by cellulase treatment assisted by Aspergillus niger or Trichoderma reesei. 36493475 1 35 theme Aspergillus 311:321 arg1 treatment 347:355 Aspergillus niger-enzyme hydrolysis treatment 311:355 Aspergillus niger-enzyme hydrolysis treatment 311:355 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 5 36 theme monosaccharide 1155:1168 arg1 composition 1170:1180 different monosaccharide composition 1145:1180 different monosaccharide composition 1145:1180 Additionally, different monosaccharide composition was exhibited due to diverse extraction methods. 36493475 1 37 theme hydrolysis 204:213 arg1 treatment 215:223 enzyme hydrolysis treatment 197:223 enzyme hydrolysis treatment 197:223 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 5 38 theme extraction 1211:1220 arg1 methods 1222:1228 diverse extraction methods 1203:1228 diverse extraction methods 1203:1228 Additionally, different monosaccharide composition was exhibited due to diverse extraction methods. 36493475 1 39 theme niger-enzyme 323:334 arg1 treatment 347:355 Aspergillus niger-enzyme hydrolysis treatment 311:355 Aspergillus niger-enzyme hydrolysis treatment 311:355 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 0 40 theme assisted 129:136 arg1 treatment 119:127 cellulase treatment assisted 109:136 cellulase treatment assisted by Aspergillus niger or Trichoderma reesei 109:179 Structural properties and adsorption capacities of Mesona chinensis Benth residues dietary fiber prepared by cellulase treatment assisted by Aspergillus niger or Trichoderma reesei. 36493475 3 41 theme soluble 752:758 arg1 yield 774:778 soluble dietary fiber yield 752:778 the highest soluble dietary fiber yield (20.76 ± 0.31 %) 740:795 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 3 41 theme soluble 752:758 arg1 % 794:794 20.76 ± 0.31 % 781:794 20.76 ± 0.31 % 781:794 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 1 42 theme treatment 215:223 arg1 effects 186:192 The effects 182:192 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues 182:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 2 43 theme Aspergillus 554:564 arg1 sample 600:605 The Aspergillus niger-enzyme hydrolysis treatment sample 550:605 The Aspergillus niger-enzyme hydrolysis treatment sample 550:605 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 1 44 theme hydrolysis 336:345 arg1 treatment 347:355 Aspergillus niger-enzyme hydrolysis treatment 311:355 Aspergillus niger-enzyme hydrolysis treatment 311:355 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 2 45 theme lower 641:645 arg1 crystallinity 647:659 lower crystallinity 641:659 lower crystallinity 641:659 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 1 46 theme soluble 462:468 arg1 fiber 478:482 soluble dietary fiber 462:482 soluble dietary fiber from Mesona chinensis Benth residues 462:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 4 47 theme high 938:941 arg1 capacity 955:962 a high oil-holding capacity 936:962 a high oil-holding capacity 936:962 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 6 48 theme residues 1359:1366 arg1 value 1327:1331 the economic value 1314:1331 the economic value of Mesona chinensis Benth residues 1314:1366 Our finding revealed that these two modification methods could effectively enhance the economic value of Mesona chinensis Benth residues. 36493475 1 49 theme treatment 347:355 arg1 effects 186:192 The effects 182:192 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues 182:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 50 theme dietary 470:476 arg1 fiber 478:482 soluble dietary fiber 462:482 soluble dietary fiber from Mesona chinensis Benth residues 462:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 51 from properties 422:431 arg1 residues 512:519 Mesona chinensis Benth residues 489:519 Mesona chinensis Benth residues 489:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 52 theme Aspergillus 226:236 arg1 treatment 257:265 Aspergillus niger fermentation treatment 226:265 Aspergillus niger fermentation treatment 226:265 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 2 53 theme other 688:692 arg1 samples 703:709 other modified samples 688:709 other modified samples 688:709 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 1 54 theme fiber 478:482 arg1 properties 422:431 structural properties 411:431 structural properties 411:431 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 54 theme fiber 478:482 arg1 capacities 448:457 adsorption capacities 437:457 adsorption capacities 437:457 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 55 theme Trichoderma 361:371 arg1 treatment 398:406 Trichoderma reesei-enzyme hydrolysis treatment 361:406 Trichoderma reesei-enzyme hydrolysis treatment 361:406 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 4 56 theme oil-holding 943:953 arg1 capacity 955:962 a high oil-holding capacity 936:962 a high oil-holding capacity 936:962 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 1 57 theme reesei-enzyme 373:385 arg1 treatment 398:406 Trichoderma reesei-enzyme hydrolysis treatment 361:406 Trichoderma reesei-enzyme hydrolysis treatment 361:406 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 4 58 theme adsorption 1031:1040 arg1 16.40 ± 0.37 mg/g 1052:1068 16.40 ± 0.37 mg/g 1052:1068 16.40 ± 0.37 mg/g 1052:1068 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 4 58 theme adsorption 1031:1040 arg1 capacity 1042:1049 cholesterol adsorption capacity 1019:1049 cholesterol adsorption capacity (16.40 ± 0.37 mg/g) 1019:1069 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 4 59 theme treatment 909:917 arg1 sample 919:924 The Aspergillus niger fermentation treatment sample 874:924 The Aspergillus niger fermentation treatment sample 874:924 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 6 60 theme modification 1267:1278 arg1 methods 1280:1286 these two modification methods 1257:1286 these two modification methods 1257:1286 Our finding revealed that these two modification methods could effectively enhance the economic value of Mesona chinensis Benth residues. 36493475 2 61 theme thermal 665:671 arg1 stability 673:681 thermal stability 665:681 thermal stability 665:681 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 3 62 theme fiber 768:772 arg1 yield 774:778 soluble dietary fiber yield 752:778 the highest soluble dietary fiber yield (20.76 ± 0.31 %) 740:795 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 3 62 theme fiber 768:772 arg1 % 794:794 20.76 ± 0.31 % 781:794 20.76 ± 0.31 % 781:794 Meanwhile, it also observed the highest soluble dietary fiber yield (20.76 ± 0.31 %), water-holding capacity and glucose adsorption capacity (38.03 ± 0.28 mg/g). 36493475 1 63 dep Aspergillus 226:236 arg1 niger 238:242 niger 238:242 niger 238:242 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 2 64 contain possessed 607:615 arg2 structure 630:638 more diverse structure 617:638 more diverse structure 617:638 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 2 64 contain possessed 607:615 arg2 stability 673:681 thermal stability 665:681 thermal stability 665:681 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 2 64 contain possessed 607:615 arg1 sample 600:605 The Aspergillus niger-enzyme hydrolysis treatment sample 550:605 The Aspergillus niger-enzyme hydrolysis treatment sample 550:605 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 2 64 contain possessed 607:615 arg2 crystallinity 647:659 lower crystallinity 641:659 lower crystallinity 641:659 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 2 65 theme treatment 590:598 arg1 sample 600:605 The Aspergillus niger-enzyme hydrolysis treatment sample 550:605 The Aspergillus niger-enzyme hydrolysis treatment sample 550:605 The Aspergillus niger-enzyme hydrolysis treatment sample possessed more diverse structure, lower crystallinity and thermal stability than other modified samples. 36493475 1 66 theme fermentation 244:255 arg1 treatment 257:265 Aspergillus niger fermentation treatment 226:265 Aspergillus niger fermentation treatment 226:265 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 0 67 theme residues 74:81 arg1 properties 11:20 Structural properties 0:20 Structural properties 0:20 Structural properties and adsorption capacities of Mesona chinensis Benth residues dietary fiber prepared by cellulase treatment assisted by Aspergillus niger or Trichoderma reesei. 36493475 0 67 theme residues 74:81 arg1 capacities 37:46 adsorption capacities 26:46 adsorption capacities 26:46 Structural properties and adsorption capacities of Mesona chinensis Benth residues dietary fiber prepared by cellulase treatment assisted by Aspergillus niger or Trichoderma reesei. 36493475 1 68 theme Benth 506:510 arg1 residues 512:519 Mesona chinensis Benth residues 489:519 Mesona chinensis Benth residues 489:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 1 69 theme treatment 257:265 arg1 effects 186:192 The effects 182:192 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues 182:519 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 0 70 theme Benth 68:72 arg1 residues 74:81 Mesona chinensis Benth residues 51:81 Mesona chinensis Benth residues 51:81 Structural properties and adsorption capacities of Mesona chinensis Benth residues dietary fiber prepared by cellulase treatment assisted by Aspergillus niger or Trichoderma reesei. 36493475 1 71 theme hydrolysis 387:396 arg1 treatment 398:406 Trichoderma reesei-enzyme hydrolysis treatment 361:406 Trichoderma reesei-enzyme hydrolysis treatment 361:406 The effects of enzyme hydrolysis treatment, Aspergillus niger fermentation treatment, Trichoderma reesei fermentation treatment, Aspergillus niger-enzyme hydrolysis treatment and Trichoderma reesei-enzyme hydrolysis treatment on structural properties and adsorption capacities of soluble dietary fiber from Mesona chinensis Benth residues were evaluated and compared. 36493475 5 72 theme different 1145:1153 arg1 composition 1170:1180 different monosaccharide composition 1145:1180 different monosaccharide composition 1145:1180 Additionally, different monosaccharide composition was exhibited due to diverse extraction methods. 36493475 4 73 theme cholate 1082:1088 arg1 94.80 ± 1.41 mg/g 1111:1127 94.80 ± 1.41 mg/g 1111:1127 94.80 ± 1.41 mg/g 1111:1127 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 36493475 4 73 theme cholate 1082:1088 arg1 capacity 1101:1108 sodium cholate adsorption capacity 1075:1108 sodium cholate adsorption capacity (94.80 ± 1.41 mg/g) 1075:1128 The Aspergillus niger fermentation treatment sample generated a high oil-holding capacity, nitrite ion adsorption capacity (181.84 ± 6.67 ug/g), cholesterol adsorption capacity (16.40 ± 0.37 mg/g) and sodium cholate adsorption capacity (94.80 ± 1.41 mg/g). 35320023 10 0 theme POMGnT1 1413:1419 arg1 overexpression 1421:1434 POMGnT1 overexpression 1413:1434 POMGnT1 overexpression 1413:1434 POMGnT1 overexpression may lower Aβ levels by reducing APP production and downregulating β- and γ-secretase activities. 35320023 2 1 gly Mannosylation 324:336 arg1 pathogenesis 415:426 the pathogenesis 411:426 the pathogenesis of AD 411:432 Mannosylation, a particular type of posttranslational modification, may be involved in the pathogenesis of AD. 35320023 7 2 theme N2a 1150:1152 arg1 cells 1154:1158 N2a cells 1150:1158 N2a cells stably transfected with Swedish mutant APP (N2a/APP) 1150:1211 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 13 3 theme pathologies.NEW 1792:1806 arg1 NOTEWORTHY 1810:1819 AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1 1784:1929 AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1 1784:1929 The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. 35320023 10 4 theme Aβ 1446:1447 arg1 levels 1449:1454 Aβ levels 1446:1454 Aβ levels 1446:1454 POMGnT1 overexpression may lower Aβ levels by reducing APP production and downregulating β- and γ-secretase activities. 35320023 1 5 theme senile 202:207 arg1 plaques 209:215 senile plaques 202:215 senile plaques 202:215 Alzheimer's disease (AD) is pathologically characterized by senile plaques and neurofibrillary tangles composed of β-amyloid peptide (Aβ) and tau hyperphosphorylation, respectively. 35320023 6 6 theme AD 967:968 arg1 mouse 970:974 AD mouse and cell models 967:990 mouse 970:974 This study aimed to investigate whether POMGnT1 participated in the pathogenesis of AD and explore its underlying role using AD mouse and cell models. 35320023 5 7 theme POMGnT1 735:741 arg1 gene 743:746 The defective POMGnT1 gene 721:746 The defective POMGnT1 gene 721:746 The defective POMGnT1 gene leads to the hypomannosylation of proteins, which may cause cognitive decline in aged people. 35320023 11 8 theme insulin-degrading 1582:1598 arg1 enzymes 1600:1606 insulin-degrading enzymes 1582:1606 insulin-degrading enzymes 1582:1606 It also promoted clearance of Aβ by upregulating insulin-degrading enzymes and ameliorated tau hyperphosphorylation. 35320023 2 9 theme particular 341:350 arg1 Mannosylation 324:336 Mannosylation 324:336 Mannosylation 324:336 Mannosylation, a particular type of posttranslational modification, may be involved in the pathogenesis of AD. 35320023 2 9 theme particular 341:350 arg1 type 352:355 a particular type 339:355 a particular type of posttranslational modification 339:389 Mannosylation, a particular type of posttranslational modification, may be involved in the pathogenesis of AD. 35320023 0 10 link O-linked 32:39 arg1 β-1,2-N-acetylglucosaminyltransferase 49:85 protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 24:87 protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 24:87 Decreased expression of protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 contributes to Alzheimer's disease-like pathologies. 35320023 13 11 from role 1845:1848 arg1 pathogenesis 1874:1885 the pathogenesis 1870:1885 the pathogenesis of AD 1870:1891 The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. 35320023 14 12 theme gene 1965:1968 arg1 overexpression 1970:1983 target gene overexpression 1958:1983 target gene overexpression 1958:1983 Results demonstrated that target gene overexpression could ameliorate pathologies of Aβ and tau hyperphosphorylation. 35320023 5 13 theme cognitive 808:816 arg1 decline 818:824 cognitive decline 808:824 cognitive decline in aged people 808:839 The defective POMGnT1 gene leads to the hypomannosylation of proteins, which may cause cognitive decline in aged people. 35320023 5 14 from decline 818:824 arg1 people 834:839 aged people 829:839 aged people 829:839 The defective POMGnT1 gene leads to the hypomannosylation of proteins, which may cause cognitive decline in aged people. 35320023 14 15 dep Aβ 2017:2018 arg1 hyperphosphorylation 2028:2047 hyperphosphorylation 2028:2047 hyperphosphorylation 2028:2047 Results demonstrated that target gene overexpression could ameliorate pathologies of Aβ and tau hyperphosphorylation. 35320023 4 16 theme O-linked 494:501 arg1 β-1,2-N-acetylglucosaminyltransferase 511:547 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 486:549 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) 486:559 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 4 16 theme O-linked 494:501 arg1 POMGnT1 552:558 POMGnT1 552:558 POMGnT1 552:558 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 8 17 theme AD 1298:1299 arg1 mouse 1301:1305 AD mouse and cell models 1298:1321 mouse 1301:1305 The results revealed that the expression of POMGnT1 decreased in AD mouse and cell models. 35320023 7 18 dep model 1143:1147 arg1 cells 1154:1158 N2a cells 1150:1158 N2a cells stably transfected with Swedish mutant APP (N2a/APP) 1150:1211 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 19 theme precursor 1071:1079 arg1 PS1 1109:1111 PS1 1109:1111 PS1 1109:1111 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 19 theme precursor 1071:1079 arg1 /presenilin-1 1094:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 1050:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model] 1050:1230 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 20 theme /presenilin-1 1094:1106 arg1 mice 1125:1128 AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice 1050:1128 AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model] 1050:1230 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 21 theme models 1053:1058 arg1 PS1 1109:1111 PS1 1109:1111 PS1 1109:1111 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 21 theme models 1053:1058 arg1 /presenilin-1 1094:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 1050:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model] 1050:1230 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 4 22 link O-linked 494:501 arg1 β-1,2-N-acetylglucosaminyltransferase 511:547 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 486:549 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) 486:559 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 4 22 link O-linked 494:501 arg1 POMGnT1 552:558 POMGnT1 552:558 POMGnT1 552:558 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 12 23 theme AD 1729:1730 arg1 process 1718:1724 the pathogenic process 1703:1724 the pathogenic process of AD 1703:1730 Hence, it was concluded that POMGnT1 was involved in the pathogenic process of AD. 35320023 10 24 theme APP 1468:1470 arg1 production 1472:1481 APP production 1468:1481 APP production 1468:1481 POMGnT1 overexpression may lower Aβ levels by reducing APP production and downregulating β- and γ-secretase activities. 35320023 0 25 theme disease-like 116:127 arg1 pathologies 129:139 Alzheimer's disease-like pathologies 104:139 Alzheimer's disease-like pathologies 104:139 Decreased expression of protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 contributes to Alzheimer's disease-like pathologies. 35320023 13 26 dep NOTEWORTHY 1810:1819 arg1 explored 1832:1839 explored 1832:1839 explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1 1832:1929 The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. 35320023 10 27 theme β- 1502:1503 arg1 activities 1521:1530 β- and γ-secretase activities 1502:1530 β- and γ-secretase activities 1502:1530 POMGnT1 overexpression may lower Aβ levels by reducing APP production and downregulating β- and γ-secretase activities. 35320023 2 28 theme AD 431:432 arg1 pathogenesis 415:426 the pathogenesis 411:426 the pathogenesis of AD 411:432 Mannosylation, a particular type of posttranslational modification, may be involved in the pathogenesis of AD. 35320023 0 29 theme mannose 41:47 arg1 β-1,2-N-acetylglucosaminyltransferase 49:85 protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 24:87 protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 24:87 Decreased expression of protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 contributes to Alzheimer's disease-like pathologies. 35320023 3 30 theme underlying 448:457 arg1 mechanism 459:467 its underlying mechanism 444:467 its underlying mechanism 444:467 However, its underlying mechanism remains unclear. 35320023 0 31 theme Decreased 0:8 arg1 expression 10:19 Decreased expression 0:19 Decreased expression of protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 0:87 Decreased expression of protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 contributes to Alzheimer's disease-like pathologies. 35320023 4 32 theme linkage 622:628 arg1 formation 575:583 the formation 571:583 the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level 571:718 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 13 33 theme AD 1890:1891 arg1 pathogenesis 1874:1885 the pathogenesis 1870:1885 the pathogenesis of AD 1870:1891 The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. 35320023 9 34 theme POMGnT1-overexpressing 1337:1358 arg1 cells 1368:1372 POMGnT1-overexpressing N2a/APP cells 1337:1372 POMGnT1-overexpressing N2a/APP cells 1337:1372 In addition, POMGnT1-overexpressing N2a/APP cells were built by retroviral transfection. 35320023 4 35 theme O-mannosylglycan 633:648 arg1 formation 575:583 the formation 571:583 the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level 571:718 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 10 36 theme γ-secretase 1509:1519 arg1 activities 1521:1530 β- and γ-secretase activities 1502:1530 β- and γ-secretase activities 1502:1530 POMGnT1 overexpression may lower Aβ levels by reducing APP production and downregulating β- and γ-secretase activities. 35320023 7 37 theme mutant 1192:1197 arg1 N2a/APP 1204:1210 N2a/APP 1204:1210 N2a/APP 1204:1210 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 37 theme mutant 1192:1197 arg1 APP 1199:1201 Swedish mutant APP 1184:1201 Swedish mutant APP (N2a/APP) 1184:1211 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 0 38 theme O-linked 32:39 arg1 β-1,2-N-acetylglucosaminyltransferase 49:85 protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 24:87 protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 24:87 Decreased expression of protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 contributes to Alzheimer's disease-like pathologies. 35320023 6 39 theme underlying 945:954 arg1 role 956:959 its underlying role 941:959 its underlying role using AD mouse and cell models 941:990 This study aimed to investigate whether POMGnT1 participated in the pathogenesis of AD and explore its underlying role using AD mouse and cell models. 35320023 0 40 theme β-1,2-N-acetylglucosaminyltransferase 49:85 arg1 expression 10:19 Decreased expression 0:19 Decreased expression of protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 0:87 Decreased expression of protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 contributes to Alzheimer's disease-like pathologies. 35320023 4 41 theme N-acetylglucosamine 592:610 arg1 linkage 622:628 the N-acetylglucosamine β-1,2-Man linkage 588:628 the N-acetylglucosamine β-1,2-Man linkage 588:628 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 2 42 theme posttranslational 360:376 arg1 modification 378:389 posttranslational modification 360:389 posttranslational modification 360:389 Mannosylation, a particular type of posttranslational modification, may be involved in the pathogenesis of AD. 35320023 9 43 theme retroviral 1388:1397 arg1 transfection 1399:1410 retroviral transfection 1388:1410 retroviral transfection 1388:1410 In addition, POMGnT1-overexpressing N2a/APP cells were built by retroviral transfection. 35320023 6 44 theme AD 926:927 arg1 pathogenesis 910:921 the pathogenesis 906:921 the pathogenesis of AD 906:927 This study aimed to investigate whether POMGnT1 participated in the pathogenesis of AD and explore its underlying role using AD mouse and cell models. 35320023 14 45 theme tau 2024:2026 arg1 pathologies 2002:2012 pathologies 2002:2012 pathologies of Aβ and tau hyperphosphorylation 2002:2047 Results demonstrated that target gene overexpression could ameliorate pathologies of Aβ and tau hyperphosphorylation. 35320023 5 46 gly hypomannosylation 761:777 arg1 proteins 782:789 proteins 782:789 proteins 782:789 The defective POMGnT1 gene leads to the hypomannosylation of proteins, which may cause cognitive decline in aged people. 35320023 4 47 theme protein 674:680 arg1 level 714:718 the protein posttranslational mannosylation level 670:718 the protein posttranslational mannosylation level 670:718 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 13 48 theme mannosylation 1853:1865 arg1 role 1845:1848 the role 1841:1848 the role of mannosylation in the pathogenesis of AD 1841:1891 The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. 35320023 14 49 theme Aβ 2017:2018 arg1 pathologies 2002:2012 pathologies 2002:2012 pathologies of Aβ and tau hyperphosphorylation 2002:2047 Results demonstrated that target gene overexpression could ameliorate pathologies of Aβ and tau hyperphosphorylation. 35320023 4 50 theme mannosylation 700:712 arg1 level 714:718 the protein posttranslational mannosylation level 670:718 the protein posttranslational mannosylation level 670:718 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 7 51 dep mice 1125:1128 arg1 model 1143:1147 an AD mouse model 1131:1147 an AD mouse model 1131:1147 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 51 dep mice 1125:1128 arg1 model 1225:1229 an AD cell model 1214:1229 an AD cell model 1214:1229 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 13 52 theme decreased 1737:1745 arg1 expression 1747:1756 The decreased expression 1733:1756 The decreased expression of POMGnT1 1733:1767 The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. 35320023 1 53 theme tau 284:286 arg1 hyperphosphorylation 288:307 tau hyperphosphorylation 284:307 tau hyperphosphorylation 284:307 Alzheimer's disease (AD) is pathologically characterized by senile plaques and neurofibrillary tangles composed of β-amyloid peptide (Aβ) and tau hyperphosphorylation, respectively. 35320023 6 54 theme cell 980:983 arg1 models 985:990 AD mouse and cell models 967:990 models 985:990 This study aimed to investigate whether POMGnT1 participated in the pathogenesis of AD and explore its underlying role using AD mouse and cell models. 35320023 7 55 theme mouse 1137:1141 arg1 model 1143:1147 an AD mouse model 1131:1147 an AD mouse model 1131:1147 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 55 theme mouse 1137:1141 arg1 model 1225:1229 an AD cell model 1214:1229 an AD cell model 1214:1229 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 11 56 theme Aβ 1563:1564 arg1 clearance 1550:1558 clearance 1550:1558 clearance of Aβ 1550:1564 It also promoted clearance of Aβ by upregulating insulin-degrading enzymes and ameliorated tau hyperphosphorylation. 35320023 13 57 theme & 1808:1808 arg1 NOTEWORTHY 1810:1819 AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1 1784:1929 AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1 1784:1929 The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. 35320023 5 58 theme defective 725:733 arg1 gene 743:746 The defective POMGnT1 gene 721:746 The defective POMGnT1 gene 721:746 The defective POMGnT1 gene leads to the hypomannosylation of proteins, which may cause cognitive decline in aged people. 35320023 7 59 theme AD 1134:1135 arg1 model 1143:1147 an AD mouse model 1131:1147 an AD mouse model 1131:1147 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 59 theme AD 1134:1135 arg1 model 1225:1229 an AD cell model 1214:1229 an AD cell model 1214:1229 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 1 60 theme β-amyloid 257:265 arg1 Aβ 276:277 Aβ 276:277 Aβ 276:277 Alzheimer's disease (AD) is pathologically characterized by senile plaques and neurofibrillary tangles composed of β-amyloid peptide (Aβ) and tau hyperphosphorylation, respectively. 35320023 1 60 theme β-amyloid 257:265 arg1 peptide 267:273 β-amyloid peptide 257:273 β-amyloid peptide (Aβ) 257:278 Alzheimer's disease (AD) is pathologically characterized by senile plaques and neurofibrillary tangles composed of β-amyloid peptide (Aβ) and tau hyperphosphorylation, respectively. 35320023 1 61 theme neurofibrillary 221:235 arg1 tangles 237:243 neurofibrillary tangles 221:243 neurofibrillary tangles 221:243 Alzheimer's disease (AD) is pathologically characterized by senile plaques and neurofibrillary tangles composed of β-amyloid peptide (Aβ) and tau hyperphosphorylation, respectively. 35320023 4 62 theme Protein 486:492 arg1 β-1,2-N-acetylglucosaminyltransferase 511:547 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 486:549 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) 486:559 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 4 62 theme Protein 486:492 arg1 POMGnT1 552:558 POMGnT1 552:558 POMGnT1 552:558 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 14 63 theme target 1958:1963 arg1 overexpression 1970:1983 target gene overexpression 1958:1983 target gene overexpression 1958:1983 Results demonstrated that target gene overexpression could ameliorate pathologies of Aβ and tau hyperphosphorylation. 35320023 4 64 theme mannose 503:509 arg1 β-1,2-N-acetylglucosaminyltransferase 511:547 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 486:549 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) 486:559 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 4 64 theme mannose 503:509 arg1 POMGnT1 552:558 POMGnT1 552:558 POMGnT1 552:558 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 8 65 theme POMGnT1 1277:1283 arg1 expression 1263:1272 the expression 1259:1272 the expression of POMGnT1 1259:1283 The results revealed that the expression of POMGnT1 decreased in AD mouse and cell models. 35320023 13 66 theme AD-like 1784:1790 arg1 NOTEWORTHY 1810:1819 AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1 1784:1929 AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1 1784:1929 The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. 35320023 7 67 theme APP 1090:1092 arg1 PS1 1109:1111 PS1 1109:1111 PS1 1109:1111 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 67 theme APP 1090:1092 arg1 /presenilin-1 1094:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 1050:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model] 1050:1230 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 5 68 theme proteins 782:789 arg1 hypomannosylation 761:777 the hypomannosylation 757:777 the hypomannosylation 757:777 The defective POMGnT1 gene leads to the hypomannosylation of proteins, which may cause cognitive decline in aged people. 35320023 7 69 theme protein 1081:1087 arg1 PS1 1109:1111 PS1 1109:1111 PS1 1109:1111 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 69 theme protein 1081:1087 arg1 /presenilin-1 1094:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 1050:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model] 1050:1230 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 70 theme [β-amyloid 1060:1069 arg1 PS1 1109:1111 PS1 1109:1111 PS1 1109:1111 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 70 theme [β-amyloid 1060:1069 arg1 /presenilin-1 1094:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 1050:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model] 1050:1230 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 8 71 theme cell 1311:1314 arg1 models 1316:1321 AD mouse and cell models 1298:1321 models 1316:1321 The results revealed that the expression of POMGnT1 decreased in AD mouse and cell models. 35320023 7 72 theme cell 1220:1223 arg1 model 1143:1147 an AD mouse model 1131:1147 an AD mouse model 1131:1147 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 72 theme cell 1220:1223 arg1 model 1225:1229 an AD cell model 1214:1229 an AD cell model 1214:1229 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 73 theme AD 1050:1051 arg1 PS1 1109:1111 PS1 1109:1111 PS1 1109:1111 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 73 theme AD 1050:1051 arg1 /presenilin-1 1094:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 1050:1106 AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model] 1050:1230 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 74 theme AD 1217:1218 arg1 model 1143:1147 an AD mouse model 1131:1147 an AD mouse model 1131:1147 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 74 theme AD 1217:1218 arg1 model 1225:1229 an AD cell model 1214:1229 an AD cell model 1214:1229 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 13 75 theme POMGnT1 1761:1767 arg1 expression 1747:1756 The decreased expression 1733:1756 The decreased expression of POMGnT1 1733:1767 The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. 35320023 5 76 theme aged 829:832 arg1 people 834:839 aged people 829:839 aged people 829:839 The defective POMGnT1 gene leads to the hypomannosylation of proteins, which may cause cognitive decline in aged people. 35320023 7 77 theme POMGnT1 1026:1032 arg1 expression 1012:1021 the expression 1008:1021 the expression of POMGnT1 1008:1032 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 12 78 theme pathogenic 1707:1716 arg1 process 1718:1724 the pathogenic process 1703:1724 the pathogenic process of AD 1703:1730 Hence, it was concluded that POMGnT1 was involved in the pathogenic process of AD. 35320023 0 79 theme protein 24:30 arg1 β-1,2-N-acetylglucosaminyltransferase 49:85 protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 24:87 protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 24:87 Decreased expression of protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 contributes to Alzheimer's disease-like pathologies. 35320023 7 80 theme Swedish 1184:1190 arg1 N2a/APP 1204:1210 N2a/APP 1204:1210 N2a/APP 1204:1210 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 7 80 theme Swedish 1184:1190 arg1 APP 1199:1201 Swedish mutant APP 1184:1201 Swedish mutant APP (N2a/APP) 1184:1211 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 9 81 theme N2a/APP 1360:1366 arg1 cells 1368:1372 POMGnT1-overexpressing N2a/APP cells 1337:1372 POMGnT1-overexpressing N2a/APP cells 1337:1372 In addition, POMGnT1-overexpressing N2a/APP cells were built by retroviral transfection. 35320023 13 82 gly mannosylation 1853:1865 arg1 AD 1890:1891 AD 1890:1891 AD 1890:1891 The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. 35320023 7 83 theme transgenic 1114:1123 arg1 mice 1125:1128 AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice 1050:1128 AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model] 1050:1230 In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. 35320023 4 84 theme β-1,2-Man 612:620 arg1 linkage 622:628 the N-acetylglucosamine β-1,2-Man linkage 588:628 the N-acetylglucosamine β-1,2-Man linkage 588:628 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 35320023 11 85 theme tau 1624:1626 arg1 hyperphosphorylation 1628:1647 tau hyperphosphorylation 1624:1647 tau hyperphosphorylation 1624:1647 It also promoted clearance of Aβ by upregulating insulin-degrading enzymes and ameliorated tau hyperphosphorylation. 35320023 2 86 theme modification 378:389 arg1 Mannosylation 324:336 Mannosylation 324:336 Mannosylation 324:336 Mannosylation, a particular type of posttranslational modification, may be involved in the pathogenesis of AD. 35320023 2 86 theme modification 378:389 arg1 type 352:355 a particular type 339:355 a particular type of posttranslational modification 339:389 Mannosylation, a particular type of posttranslational modification, may be involved in the pathogenesis of AD. 35320023 4 87 theme posttranslational 682:698 arg1 level 714:718 the protein posttranslational mannosylation level 670:718 the protein posttranslational mannosylation level 670:718 Protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. 37082174 2 0 theme microbiota 389:398 arg1 dysbiosis 400:408 microbiota dysbiosis 389:408 microbiota dysbiosis 389:408 Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. 37082174 4 1 theme respiratory 644:654 arg1 failure 656:662 respiratory failure 644:662 respiratory failure 644:662 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). 37082174 7 2 theme phyla 1147:1151 arg1 Proteobacteria 1153:1166 phyla Proteobacteria 1147:1166 phyla Proteobacteria 1147:1166 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 2 3 theme Risk 314:317 arg1 factors 319:325 Risk factors 314:325 Risk factors for CRE acquisition 314:345 Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. 37082174 1 4 theme ill 300:302 arg1 patients 304:311 critically ill patients 289:311 critically ill patients 289:311 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 12 5 theme ill 2103:2105 arg1 patients 2107:2114 Critically ill patients 2092:2114 Critically ill patients with CRE 2092:2123 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 2 6 from use 381:383 arg1 patients 428:435 critically ill patients 413:435 critically ill patients 413:435 Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. 37082174 4 7 theme care 718:721 arg1 ICU 729:731 ICU 729:731 ICU 729:731 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). 37082174 4 7 theme care 718:721 arg1 unit 723:726 the intensive care unit 704:726 the intensive care unit (ICU) 704:732 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). 37082174 3 8 from colonization 526:537 arg1 patients 557:564 critically ill patients 542:564 critically ill patients 542:564 Therefore, we evaluated the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients. 37082174 12 9 theme short-chain 2204:2214 arg1 production 2227:2236 altered short-chain fatty acid production 2196:2236 altered short-chain fatty acid production 2196:2236 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 7 10 theme increased 1119:1127 arg1 proportion 1129:1138 a significantly increased proportion 1103:1138 a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes 1103:1215 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 12 11 contain have 2125:2128 arg2 changes 2242:2248 changes 2242:2248 changes in the metabolic pathways 2242:2274 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 12 11 contain have 2125:2128 arg2 structure 2185:2193 community structure 2175:2193 community structure 2175:2193 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 12 11 contain have 2125:2128 arg2 production 2227:2236 altered short-chain fatty acid production 2196:2236 altered short-chain fatty acid production 2196:2236 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 12 11 contain have 2125:2128 arg2 composition 2159:2169 a distinctive gut microbiota composition 2130:2169 a distinctive gut microbiota composition 2130:2169 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 12 11 contain have 2125:2128 arg1 patients 2107:2114 Critically ill patients 2092:2114 Critically ill patients with CRE 2092:2123 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 1 12 theme global 219:224 arg1 health 226:231 global health 219:231 global health 219:231 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 8 13 theme discriminant 1301:1312 arg1 size 1321:1324 linear discriminant effect size 1294:1324 linear discriminant effect size 1294:1324 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 11 14 theme significant 1841:1851 arg1 differences 1853:1863 significant differences 1841:1863 significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups 1841:2078 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 5 15 theme microbiota 743:752 arg1 profile 754:760 The gut microbiota profile 735:760 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids 735:864 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 8 16 theme Linear 1254:1259 arg1 LDA 1284:1286 LDA 1284:1286 LDA 1284:1286 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 8 16 theme Linear 1254:1259 arg1 analysis 1274:1281 Linear discriminant analysis 1254:1281 Linear discriminant analysis (LDA) with linear discriminant effect size 1254:1324 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 6 17 theme metabolic 967:975 arg1 abundance 977:985 bacterial metabolic abundance 957:985 bacterial metabolic abundance 957:985 The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway was performed. 37082174 8 18 theme LDA 1456:1458 arg1 score 1460:1464 an upper 2 LDA score 1445:1464 an upper 2 LDA score in CRE carriers 1445:1480 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 11 19 theme other 1981:1985 arg1 degradation 1994:2004 other glycan degradation 1981:2004 other glycan degradation 1981:2004 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 12 20 theme fatty 2216:2220 arg1 production 2227:2236 altered short-chain fatty acid production 2196:2236 altered short-chain fatty acid production 2196:2236 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 10 21 theme short-chain 1660:1670 arg1 acids 1678:1682 short-chain fatty acids 1660:1682 short-chain fatty acids 1660:1682 Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. 37082174 12 22 from structure 2185:2193 arg1 pathways 2267:2274 the metabolic pathways 2253:2274 the metabolic pathways 2253:2274 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 9 23 theme alpha-diversity 1487:1501 arg1 indices 1503:1509 The alpha-diversity indices 1483:1509 The alpha-diversity indices 1483:1509 The alpha-diversity indices were significantly decreased in CRE carriers, and beta-diversity analysis demonstrated that the two groups were clustered significantly apart. 37082174 7 24 theme Results 1075:1081 arg1 carriers 1087:1094 Results CRE carriers 1075:1094 Results CRE carriers 1075:1094 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 1 25 theme Carbapenem-resistant 145:164 arg1 Enterobacteriaceae 166:183 Background Carbapenem-resistant Enterobacteriaceae 134:183 Background Carbapenem-resistant Enterobacteriaceae (CRE) 134:189 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 1 25 theme Carbapenem-resistant 145:164 arg1 concern 207:213 an emerging concern 195:213 an emerging concern for global health 195:231 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 1 25 theme Carbapenem-resistant 145:164 arg1 CRE 186:188 CRE 186:188 CRE 186:188 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 6 26 theme metabolic 1042:1050 arg1 pathway 1052:1058 metabolic pathway 1042:1058 metabolic pathway 1042:1058 The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway was performed. 37082174 12 27 theme distinctive 2132:2142 arg1 composition 2159:2169 a distinctive gut microbiota composition 2130:2169 a distinctive gut microbiota composition 2130:2169 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 0 28 theme carbapenem-resistant 59:78 arg1 colonization 99:110 carbapenem-resistant Enterobacteriaceae colonization 59:110 carbapenem-resistant Enterobacteriaceae colonization 59:110 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis. 37082174 9 29 theme CRE 1543:1545 arg1 carriers 1547:1554 CRE carriers 1543:1554 CRE carriers 1543:1554 The alpha-diversity indices were significantly decreased in CRE carriers, and beta-diversity analysis demonstrated that the two groups were clustered significantly apart. 37082174 0 30 from alterations 15:25 arg1 patients 45:52 critically Ill patients 30:52 critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization 30:110 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis. 37082174 12 31 theme microbiota 2148:2157 arg1 composition 2159:2169 a distinctive gut microbiota composition 2130:2169 a distinctive gut microbiota composition 2130:2169 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 13 32 with patients 2386:2393 arg1 CRE 2400:2402 CRE 2400:2402 CRE 2400:2402 Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE. 37082174 12 33 from changes 2242:2248 arg1 pathways 2267:2274 the metabolic pathways 2253:2274 the metabolic pathways 2253:2274 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 5 34 theme = 925:925 arg1 n 923:923 n = 32 923:928 n = 32 923:928 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 5 34 theme = 925:925 arg1 patients 931:938 CRE-positive (n = 9) and CRE negative (n = 32) patients 884:938 CRE-positive (n = 9) and CRE negative (n = 32) patients 884:938 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 4 35 theme Methods 567:573 arg1 samples 581:587 Methods Fecal samples 567:587 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure 567:662 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). 37082174 11 36 theme PICRUSt-predicted 1795:1811 arg1 pathways 1823:1830 the PICRUSt-predicted metabolic pathways 1791:1830 the PICRUSt-predicted metabolic pathways 1791:1830 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 5 37 theme 16S 779:781 arg1 sequencing 793:802 16S rRNA gene sequencing 779:802 16S rRNA gene sequencing 779:802 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 12 38 from production 2227:2236 arg1 pathways 2267:2274 the metabolic pathways 2253:2274 the metabolic pathways 2253:2274 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 0 39 dep analysis 124:131 arg1 alterations 15:25 Gut microbiota alterations 0:25 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization 0:110 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis. 37082174 3 40 theme CRE 522:524 arg1 colonization 526:537 CRE colonization 522:537 CRE colonization in critically ill patients 522:564 Therefore, we evaluated the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients. 37082174 11 41 theme glycan 1987:1992 arg1 degradation 1994:2004 other glycan degradation 1981:2004 other glycan degradation 1981:2004 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 5 42 theme gene 788:791 arg1 sequencing 793:802 16S rRNA gene sequencing 779:802 16S rRNA gene sequencing 779:802 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 11 43 theme cassette 1905:1912 arg1 transporters 1914:1925 ATP-binding cassette transporters 1893:1925 ATP-binding cassette transporters 1893:1925 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 0 44 theme Gut 0:2 arg1 alterations 15:25 Gut microbiota alterations 0:25 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization 0:110 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis. 37082174 13 45 theme amino 2325:2329 arg1 acids 2331:2335 amino acids 2325:2335 amino acids supplementation 2325:2351 Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE. 37082174 8 46 contain had 1441:1443 arg1 genera 1342:1347 the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes 1338:1439 the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes 1338:1439 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 8 46 contain had 1441:1443 arg2 score 1460:1464 an upper 2 LDA score 1445:1464 an upper 2 LDA score in CRE carriers 1445:1480 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 13 47 from dysbiosis 2373:2381 arg1 patients 2386:2393 patients 2386:2393 patients with CRE 2386:2402 Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE. 37082174 11 48 theme microbial 2011:2019 arg1 metabolism 2021:2030 microbial metabolism 2011:2030 microbial metabolism 2011:2030 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 13 49 theme microbiota 2362:2371 arg1 dysbiosis 2373:2381 microbiota dysbiosis 2362:2381 microbiota dysbiosis in patients with CRE 2362:2402 Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE. 37082174 12 50 dep Conclusion 2081:2090 arg1 have 2125:2128 have 2125:2128 have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways 2125:2274 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 10 51 theme isobutyric 1699:1708 arg1 acid 1710:1713 isobutyric acid 1699:1713 isobutyric acid 1699:1713 Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. 37082174 3 52 theme microbiota 495:504 arg1 alteration 466:475 the alteration 462:475 the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients 462:564 Therefore, we evaluated the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients. 37082174 5 53 theme fecal 836:840 arg1 acids 860:864 fecal short-chain fatty acids 836:864 fecal short-chain fatty acids 836:864 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 5 54 theme fatty 854:858 arg1 acids 860:864 fecal short-chain fatty acids 836:864 fecal short-chain fatty acids 836:864 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 10 55 theme acid 1727:1730 arg1 levels 1689:1694 the levels 1685:1694 the levels of isobutyric acid and valeric acid 1685:1730 Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. 37082174 5 56 dep CRE-positive 884:895 arg1 n 898:898 n = 9 898:902 n = 9 898:902 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 0 57 with patients 45:52 arg1 colonization 99:110 carbapenem-resistant Enterobacteriaceae colonization 59:110 carbapenem-resistant Enterobacteriaceae colonization 59:110 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis. 37082174 11 58 theme sphingolipid 1956:1967 arg1 metabolism 1969:1978 sphingolipid metabolism 1956:1978 sphingolipid metabolism 1956:1978 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 12 59 theme acid 2222:2225 arg1 production 2227:2236 altered short-chain fatty acid production 2196:2236 altered short-chain fatty acid production 2196:2236 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 5 60 theme short-chain 842:852 arg1 acids 860:864 fecal short-chain fatty acids 836:864 fecal short-chain fatty acids 836:864 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 8 61 from score 1460:1464 arg1 carriers 1473:1480 CRE carriers 1469:1480 CRE carriers 1469:1480 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 7 62 theme Proteobacteria 1153:1166 arg1 proportion 1129:1138 a significantly increased proportion 1103:1138 a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes 1103:1215 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 4 63 theme septic 628:633 arg1 shock 635:639 septic shock 628:639 septic shock 628:639 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). 37082174 5 64 theme acids 860:864 arg1 sequencing 793:802 16S rRNA gene sequencing 779:802 16S rRNA gene sequencing 779:802 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 5 64 theme acids 860:864 arg1 measurement 821:831 quantitative measurement 808:831 quantitative measurement of fecal short-chain fatty acids 808:864 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 1 65 theme emerging 198:205 arg1 Enterobacteriaceae 166:183 Background Carbapenem-resistant Enterobacteriaceae 134:183 Background Carbapenem-resistant Enterobacteriaceae (CRE) 134:189 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 1 65 theme emerging 198:205 arg1 concern 207:213 an emerging concern 195:213 an emerging concern for global health 195:231 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 7 66 theme numbers 1182:1188 arg1 proportion 1129:1138 a significantly increased proportion 1103:1138 a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes 1103:1215 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 11 67 from differences 1853:1863 arg1 transporters 1914:1925 ATP-binding cassette transporters 1893:1925 ATP-binding cassette transporters 1893:1925 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 11 67 from differences 1853:1863 arg1 metabolism 2021:2030 microbial metabolism 2011:2030 microbial metabolism 2011:2030 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 11 67 from differences 1853:1863 arg1 features 1873:1880 five features 1868:1880 five features 1868:1880 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 11 67 from differences 1853:1863 arg1 degradation 1994:2004 other glycan degradation 1981:2004 other glycan degradation 1981:2004 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 11 67 from differences 1853:1863 arg1 systems 1947:1953 phosphotransferase systems 1928:1953 phosphotransferase systems 1928:1953 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 11 67 from differences 1853:1863 arg1 environments 2044:2055 diverse environments 2036:2055 diverse environments 2036:2055 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 11 67 from differences 1853:1863 arg1 metabolism 1969:1978 sphingolipid metabolism 1956:1978 sphingolipid metabolism 1956:1978 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 2 68 from dysbiosis 400:408 arg1 patients 428:435 critically ill patients 413:435 critically ill patients 413:435 Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. 37082174 4 69 theme intensive 708:716 arg1 ICU 729:731 ICU 729:731 ICU 729:731 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). 37082174 4 69 theme intensive 708:716 arg1 unit 723:726 the intensive care unit 704:726 the intensive care unit (ICU) 704:732 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). 37082174 7 70 dep Proteobacteria 1153:1166 arg1 Bacteroidetes 1203:1215 Bacteroidetes 1203:1215 Bacteroidetes 1203:1215 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 7 70 dep Proteobacteria 1153:1166 arg1 the 1143:1145 the 1143:1145 the 1143:1145 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 5 71 theme gut 739:741 arg1 profile 754:760 The gut microbiota profile 735:760 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids 735:864 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 2 72 theme CRE 331:333 arg1 acquisition 335:345 CRE acquisition 331:345 CRE acquisition 331:345 Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. 37082174 5 73 theme CRE-positive 884:895 arg1 n 923:923 n = 32 923:928 n = 32 923:928 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 5 73 theme CRE-positive 884:895 arg1 patients 931:938 CRE-positive (n = 9) and CRE negative (n = 32) patients 884:938 CRE-positive (n = 9) and CRE negative (n = 32) patients 884:938 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 6 74 theme abundance 977:985 arg1 analysis 945:952 The analysis 941:952 The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway 941:1058 The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway was performed. 37082174 8 75 theme linear 1294:1299 arg1 size 1321:1324 linear discriminant effect size 1294:1324 linear discriminant effect size 1294:1324 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 10 76 theme fatty 1672:1676 arg1 acids 1678:1682 short-chain fatty acids 1660:1682 short-chain fatty acids 1660:1682 Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. 37082174 11 77 theme phosphotransferase 1928:1945 arg1 systems 1947:1953 phosphotransferase systems 1928:1953 phosphotransferase systems 1928:1953 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 1 78 from mortality 276:284 arg1 patients 304:311 critically ill patients 289:311 critically ill patients 289:311 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 11 79 theme diverse 2036:2042 arg1 environments 2044:2055 diverse environments 2036:2055 diverse environments 2036:2055 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 6 80 theme bacterial 957:965 arg1 abundance 977:985 bacterial metabolic abundance 957:985 bacterial metabolic abundance 957:985 The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway was performed. 37082174 8 81 theme CRE 1469:1471 arg1 carriers 1473:1480 CRE carriers 1469:1480 CRE carriers 1469:1480 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 8 82 theme effect 1314:1319 arg1 size 1321:1324 linear discriminant effect size 1294:1324 linear discriminant effect size 1294:1324 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 7 83 theme CRE 1236:1238 arg1 non-carriers 1240:1251 the CRE non-carriers 1232:1251 the CRE non-carriers 1232:1251 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 1 84 from morbidity 262:270 arg1 patients 304:311 critically ill patients 289:311 critically ill patients 289:311 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 12 85 with patients 2107:2114 arg1 CRE 2121:2123 CRE 2121:2123 CRE 2121:2123 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 1 86 theme Background 134:143 arg1 Enterobacteriaceae 166:183 Background Carbapenem-resistant Enterobacteriaceae 134:183 Background Carbapenem-resistant Enterobacteriaceae (CRE) 134:189 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 1 86 theme Background 134:143 arg1 concern 207:213 an emerging concern 195:213 an emerging concern for global health 195:231 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 1 86 theme Background 134:143 arg1 CRE 186:188 CRE 186:188 CRE 186:188 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 8 87 theme discriminant 1261:1272 arg1 LDA 1284:1286 LDA 1284:1286 LDA 1284:1286 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 8 87 theme discriminant 1261:1272 arg1 analysis 1274:1281 Linear discriminant analysis 1254:1281 Linear discriminant analysis (LDA) with linear discriminant effect size 1254:1324 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 12 88 from composition 2159:2169 arg1 pathways 2267:2274 the metabolic pathways 2253:2274 the metabolic pathways 2253:2274 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 8 89 with analysis 1274:1281 arg1 size 1321:1324 linear discriminant effect size 1294:1324 linear discriminant effect size 1294:1324 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 12 90 theme community 2175:2183 arg1 structure 2185:2193 community structure 2175:2193 community structure 2175:2193 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 2 91 theme antibiotic 370:379 arg1 use 381:383 broad-spectrum antibiotic use 355:383 broad-spectrum antibiotic use 355:383 Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. 37082174 0 92 theme Enterobacteriaceae 80:97 arg1 colonization 99:110 carbapenem-resistant Enterobacteriaceae colonization 59:110 carbapenem-resistant Enterobacteriaceae colonization 59:110 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis. 37082174 12 93 theme altered 2196:2202 arg1 production 2227:2236 altered short-chain fatty acid production 2196:2236 altered short-chain fatty acid production 2196:2236 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 5 94 theme negative 913:920 arg1 n 923:923 n = 32 923:928 n = 32 923:928 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 5 94 theme negative 913:920 arg1 patients 931:938 CRE-positive (n = 9) and CRE negative (n = 32) patients 884:938 CRE-positive (n = 9) and CRE negative (n = 32) patients 884:938 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 5 95 theme quantitative 808:819 arg1 measurement 821:831 quantitative measurement 808:831 quantitative measurement of fecal short-chain fatty acids 808:864 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 6 96 theme CRE 1022:1024 arg1 acquisition 1026:1036 CRE acquisition 1022:1036 CRE acquisition 1022:1036 The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway was performed. 37082174 4 97 theme Fecal 575:579 arg1 samples 581:587 Methods Fecal samples 567:587 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure 567:662 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). 37082174 12 98 theme gut 2144:2146 arg1 composition 2159:2169 a distinctive gut microbiota composition 2130:2169 a distinctive gut microbiota composition 2130:2169 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 0 99 theme clinical 115:122 arg1 analysis 124:131 A clinical analysis 113:131 A clinical analysis 113:131 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis. 37082174 9 100 theme beta-diversity 1561:1574 arg1 analysis 1576:1583 beta-diversity analysis 1561:1583 beta-diversity analysis 1561:1583 The alpha-diversity indices were significantly decreased in CRE carriers, and beta-diversity analysis demonstrated that the two groups were clustered significantly apart. 37082174 10 101 theme valeric 1719:1725 arg1 acid 1727:1730 valeric acid 1719:1730 valeric acid 1719:1730 Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. 37082174 5 102 theme rRNA 783:786 arg1 sequencing 793:802 16S rRNA gene sequencing 779:802 16S rRNA gene sequencing 779:802 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 11 103 theme metabolic 1813:1821 arg1 pathways 1823:1830 the PICRUSt-predicted metabolic pathways 1791:1830 the PICRUSt-predicted metabolic pathways 1791:1830 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 37082174 13 104 theme Further 2277:2283 arg1 studies 2285:2291 Further studies 2277:2291 Further studies 2277:2291 Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE. 37082174 3 105 theme intestinal 484:493 arg1 microbiota 495:504 the intestinal microbiota 480:504 the intestinal microbiota associated with CRE colonization in critically ill patients 480:564 Therefore, we evaluated the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients. 37082174 0 106 theme microbiota 4:13 arg1 alterations 15:25 Gut microbiota alterations 0:25 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization 0:110 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis. 37082174 7 107 theme CRE 1083:1085 arg1 carriers 1087:1094 Results CRE carriers 1075:1094 Results CRE carriers 1075:1094 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 2 108 theme ill 424:426 arg1 patients 428:435 critically ill patients 413:435 critically ill patients 413:435 Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. 37082174 7 109 theme phyla 1197:1201 arg1 Proteobacteria 1153:1166 phyla Proteobacteria 1147:1166 phyla Proteobacteria 1147:1166 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 7 109 theme phyla 1197:1201 arg1 numbers 1182:1188 decreased numbers 1172:1188 decreased numbers of the phyla 1172:1201 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 13 110 theme acids 2331:2335 arg1 supplementation 2337:2351 amino acids supplementation 2325:2351 amino acids supplementation 2325:2351 Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE. 37082174 10 111 theme acid 1710:1713 arg1 levels 1689:1694 the levels 1685:1694 the levels of isobutyric acid and valeric acid 1685:1730 Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. 37082174 0 112 theme Ill 41:43 arg1 patients 45:52 critically Ill patients 30:52 critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization 30:110 Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis. 37082174 7 113 theme decreased 1172:1180 arg1 numbers 1182:1188 decreased numbers 1172:1188 decreased numbers of the phyla 1172:1201 Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. 37082174 4 114 theme patients 595:602 arg1 samples 581:587 Methods Fecal samples 567:587 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure 567:662 Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). 37082174 3 115 theme ill 553:555 arg1 patients 557:564 critically ill patients 542:564 critically ill patients 542:564 Therefore, we evaluated the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients. 37082174 12 116 theme metabolic 2257:2265 arg1 pathways 2267:2274 the metabolic pathways 2253:2274 the metabolic pathways 2253:2274 Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. 37082174 8 117 dep genera 1342:1347 arg1 Alistipes 1431:1439 Alistipes 1431:1439 Alistipes 1431:1439 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 8 117 dep genera 1342:1347 arg1 Citrobacter 1358:1368 Citrobacter 1358:1368 Citrobacter 1358:1368 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 8 117 dep genera 1342:1347 arg1 Kluyvera 1396:1403 Kluyvera 1396:1403 Kluyvera 1396:1403 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 8 117 dep genera 1342:1347 arg1 Dysgomonas 1406:1415 Dysgomonas 1406:1415 Dysgomonas 1406:1415 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 8 117 dep genera 1342:1347 arg1 Klebsiella 1371:1380 Klebsiella 1371:1380 Klebsiella 1371:1380 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 8 117 dep genera 1342:1347 arg1 Pantoea 1418:1424 Pantoea 1418:1424 Pantoea 1418:1424 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 2 118 theme broad-spectrum 355:368 arg1 use 381:383 broad-spectrum antibiotic use 355:383 broad-spectrum antibiotic use 355:383 Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. 37082174 1 119 theme high 257:260 arg1 morbidity 262:270 morbidity 262:270 morbidity 262:270 Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. 37082174 5 120 theme = 900:900 arg1 n 898:898 n = 9 898:902 n = 9 898:902 The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. 37082174 8 121 theme upper 1448:1452 arg1 score 1460:1464 an upper 2 LDA score 1445:1464 an upper 2 LDA score in CRE carriers 1445:1480 Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. 37082174 10 122 theme CRE 1764:1766 arg1 carriers 1768:1775 CRE carriers 1764:1775 CRE carriers 1764:1775 Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. 37082174 11 123 theme ATP-binding 1893:1903 arg1 transporters 1914:1925 ATP-binding cassette transporters 1893:1925 ATP-binding cassette transporters 1893:1925 Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. 36998438 12 0 theme metabolism 2430:2439 arg1 pathways 2441:2448 amino acid metabolism pathways 2419:2448 amino acid metabolism pathways 2419:2448 The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. 36998438 13 1 theme ileostomy 2468:2476 arg1 surgery 2486:2492 ileostomy closure surgery 2468:2492 ileostomy closure surgery 2468:2492 Conclusion After ileostomy closure surgery, a series of severe clinical symptoms might appear in DC patients. 36998438 1 2 theme continuity 252:261 arg1 disruption 230:239 disruption 230:239 disruption of colonic continuity with colonic dysfunction 230:286 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 6 3 theme baseline 893:900 arg1 information 902:912 comparethe clinical baseline information 873:912 comparethe clinical baseline information 873:912 We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. 36998438 11 4 with flora 2106:2110 arg1 values 2133:2138 high enrichment values 2117:2138 high enrichment values 2117:2138 The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. 36998438 12 5 theme such 2310:2313 arg1 types 2319:2323 such two types 2310:2323 such two types of intestinal flora 2310:2343 The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. 36998438 10 6 theme propsective 1886:1896 arg1 study 1914:1918 propsective oberservational study 1886:1918 propsective oberservational study 1886:1918 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 6 theme propsective 1886:1896 arg1 patients 1924:1931 40 patients 1921:1931 40 patients with low rectal cancer recruited by sample size calculation 1921:1991 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 1 7 theme colonic 268:274 arg1 dysfunction 276:286 colonic dysfunction 268:286 colonic dysfunction 268:286 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 6 8 theme comparethe 873:882 arg1 information 902:912 comparethe clinical baseline information 873:912 comparethe clinical baseline information 873:912 We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. 36998438 14 9 theme DC 2681:2682 arg1 patients 2684:2691 DC patients 2681:2691 DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma 2681:2830 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 4 10 theme Anorectal 651:659 arg1 Surgery 661:667 Anorectal Surgery 651:667 Anorectal Surgery 651:667 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 4 10 theme Anorectal 651:659 arg1 Hospital 681:688 Hospital 681:688 Hospital 681:688 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 7 11 theme ileum 1124:1128 arg1 enterostomy 1130:1140 terminal ileum enterostomy 1115:1140 terminal ileum enterostomy 1115:1140 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 10 12 theme risk 1701:1704 arg1 factors 1706:1712 independent risk factors 1689:1712 independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy 1689:1880 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 14 13 theme interventional 2767:2780 arg1 treatment 2782:2790 the clinical interventional treatment 2754:2790 the clinical interventional treatment for DC in patients with permanent stoma 2754:2830 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 12 14 theme amino 2419:2423 arg1 pathways 2441:2448 amino acid metabolism pathways 2419:2448 amino acid metabolism pathways 2419:2448 The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. 36998438 10 15 theme diarrhea 1740:1747 arg1 consistent 1800:1809 consistent 1800:1809 consistent 1800:1809 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 15 theme diarrhea 1740:1747 arg1 severity 1728:1735 the severity 1724:1735 the severity 1724:1735 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 6 16 theme different 974:982 arg1 severity 984:991 different severity 974:991 different severity of DC 974:997 We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. 36998438 11 17 theme severe 2231:2236 arg1 group 2238:2242 the severe group 2227:2242 the severe group 2227:2242 The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. 36998438 10 18 from group 2014:2018 arg1 group 2041:2045 the severe group 2030:2045 the severe group 2030:2045 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 18 from group 2014:2018 arg1 study 1914:1918 propsective oberservational study 1886:1918 propsective oberservational study 1886:1918 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 18 from group 2014:2018 arg1 patients 1924:1931 40 patients 1921:1931 40 patients with low rectal cancer recruited by sample size calculation 1921:1991 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 0 19 theme rectal 111:116 arg1 cancer 118:123 rectal cancer 111:123 rectal cancer 111:123 Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer. 36998438 14 20 with patients 2684:2691 arg1 scores 2720:2725 different colonscopic scores 2698:2725 different colonscopic scores 2698:2725 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 9 21 dep Results 1419:1425 arg1 found 1454:1458 found 1454:1458 found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05) 1454:1606 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 10 22 theme rectal 1942:1947 arg1 cancer 1949:1954 low rectal cancer 1938:1954 low rectal cancer 1938:1954 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 7 23 theme anterior 1078:1085 arg1 resection 1091:1099 laparoscopic anterior low resection 1065:1099 laparoscopic anterior low resection combined with terminal ileum enterostomy 1065:1140 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 5 24 theme terminal 803:810 arg1 enterostomy 818:828 terminal ileum enterostomy 803:828 terminal ileum enterostomy (dual-chamber) 803:843 These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). 36998438 1 25 theme intestinal 202:211 arg1 mucosa 213:218 the distal intestinal mucosa 191:218 the distal intestinal mucosa 191:218 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 14 26 theme permanent 2816:2824 arg1 stoma 2826:2830 permanent stoma 2816:2830 permanent stoma 2816:2830 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 10 27 theme ileostomy 1755:1763 arg1 surgery 1773:1779 ileostomy closure surgery 1755:1779 ileostomy closure surgery(P<0.05) 1755:1787 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 27 theme ileostomy 1755:1763 arg1 P<0.05 1781:1786 P<0.05 1781:1786 P<0.05 1781:1786 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 7 28 theme oberservational 1012:1026 arg1 study 1028:1032 Propsective oberservational study 1000:1032 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 1000:1266 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 9 29 theme diabetes 1486:1493 arg1 BMI 1470:1472 BMI 1470:1472 BMI 1470:1472 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 29 theme diabetes 1486:1493 arg1 age 1465:1467 age 1465:1467 age 1465:1467 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 29 theme diabetes 1486:1493 arg1 factors 1567:1573 the independent risk factors 1546:1573 the independent risk factors that affect DC severity (P<0.05) 1546:1606 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 29 theme diabetes 1486:1493 arg1 symptoms 1500:1507 symptoms 1500:1507 symptoms associated with the stoma state 1500:1539 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 29 theme diabetes 1486:1493 arg1 history 1475:1481 history 1475:1481 history of diabetes 1475:1493 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 10 30 theme sample 1969:1974 arg1 calculation 1981:1991 sample size calculation 1969:1991 sample size calculation 1969:1991 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 9 31 theme retrospective 1430:1442 arg1 study 1444:1448 retrospective study 1430:1448 retrospective study 1430:1448 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 1 32 theme Background 126:135 arg1 colitis 147:153 Background Diversion colitis 126:153 Background Diversion colitis (DC) 126:158 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 1 32 theme Background 126:135 arg1 DC 156:157 DC 156:157 DC 156:157 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 14 33 theme colonscopic 2708:2718 arg1 scores 2720:2725 different colonscopic scores 2698:2725 different colonscopic scores 2698:2725 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 5 34 theme laparoscopic 747:758 arg1 LAR 784:786 LAR 784:786 LAR 784:786 These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). 36998438 5 34 theme laparoscopic 747:758 arg1 resection 773:781 laparoscopic low anterior resection 747:781 laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber) 747:843 These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). 36998438 8 35 theme intestinal 1352:1361 arg1 flora 1363:1367 intestinal flora 1352:1367 intestinal flora 1352:1367 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. 36998438 0 36 theme colitis 71:77 arg1 Interaction 0:10 Interaction 0:10 Interaction between the intestinal flora 0:39 Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer. 36998438 0 36 theme colitis 71:77 arg1 severity 49:56 the severity 45:56 the severity of diversion colitis 45:77 Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer. 36998438 12 37 theme acid 2425:2428 arg1 pathways 2441:2448 amino acid metabolism pathways 2419:2448 amino acid metabolism pathways 2419:2448 The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. 36998438 0 38 theme low 85:87 arg1 resection 98:106 low anterior resection 85:106 low anterior resection of rectal cancer 85:123 Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer. 36998438 8 39 theme intestinal 1376:1385 arg1 fluid 1394:1398 the intestinal lavage fluid 1372:1398 the intestinal lavage fluid of the two groups 1372:1416 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. 36998438 7 40 dep study 1028:1032 arg1 recruited 1038:1046 recruited 1038:1046 recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy 1038:1140 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 7 40 dep study 1028:1032 arg1 classified 1164:1173 classified 1164:1173 were further classified into mild group and severe group according to the scores of colonscopic examinations for DC 1151:1265 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 0 41 theme diversion 61:69 arg1 colitis 71:77 diversion colitis 61:77 diversion colitis 61:77 Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer. 36998438 13 42 theme severe 2507:2512 arg1 symptoms 2523:2530 severe clinical symptoms 2507:2530 severe clinical symptoms 2507:2530 Conclusion After ileostomy closure surgery, a series of severe clinical symptoms might appear in DC patients. 36998438 13 43 theme clinical 2514:2521 arg1 symptoms 2523:2530 severe clinical symptoms 2507:2530 severe clinical symptoms 2507:2530 Conclusion After ileostomy closure surgery, a series of severe clinical symptoms might appear in DC patients. 36998438 8 44 from differences 1337:1347 arg1 fluid 1394:1398 the intestinal lavage fluid 1372:1398 the intestinal lavage fluid of the two groups 1372:1416 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. 36998438 9 45 theme risk 1562:1565 arg1 BMI 1470:1472 BMI 1470:1472 BMI 1470:1472 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 45 theme risk 1562:1565 arg1 age 1465:1467 age 1465:1467 age 1465:1467 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 45 theme risk 1562:1565 arg1 factors 1567:1573 the independent risk factors 1546:1573 the independent risk factors that affect DC severity (P<0.05) 1546:1606 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 45 theme risk 1562:1565 arg1 symptoms 1500:1507 symptoms 1500:1507 symptoms associated with the stoma state 1500:1539 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 45 theme risk 1562:1565 arg1 history 1475:1481 history 1475:1481 history of diabetes 1475:1493 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 11 46 theme sequencing 2072:2081 arg1 results 2052:2058 The results 2048:2058 The results of 16s-rDNA sequencing 2048:2081 The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. 36998438 10 47 theme diabetes 1641:1648 arg1 score 1666:1670 colonscopic score 1654:1670 colonscopic score 1654:1670 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 47 theme diabetes 1641:1648 arg1 history 1630:1636 history 1630:1636 history of diabetes 1630:1648 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 47 theme diabetes 1641:1648 arg1 BMI 1625:1627 BMI 1625:1627 BMI 1625:1627 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 47 theme diabetes 1641:1648 arg1 age 1620:1622 age 1620:1622 age 1620:1622 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 47 theme diabetes 1641:1648 arg1 Meanwhile 1609:1617 Meanwhile 1609:1617 Meanwhile 1609:1617 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 5 48 theme ileum 812:816 arg1 enterostomy 818:828 terminal ileum enterostomy 803:828 terminal ileum enterostomy (dual-chamber) 803:843 These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). 36998438 6 49 theme chi-square 854:863 arg1 test 865:868 chi-square test 854:868 chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC 854:997 We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. 36998438 4 50 dep April 696:700 arg1 to 707:708 to 707:708 to 707:708 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 4 50 dep April 696:700 arg1 April 710:714 April 710:714 April 710:714 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 14 51 theme intestinal 2656:2665 arg1 flora 2667:2671 intestinal flora 2656:2671 intestinal flora 2656:2671 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 11 52 theme high 2117:2120 arg1 values 2133:2138 high enrichment values 2117:2138 high enrichment values 2117:2138 The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. 36998438 4 53 theme Clinical 548:555 arg1 information 557:567 Clinical information 548:567 Clinical information 548:567 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 11 54 dep consisted 2150:2158 arg1 whereas 2211:2217 whereas 2211:2217 whereas 2211:2217 The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. 36998438 8 55 theme groups 1411:1416 arg1 fluid 1394:1398 the intestinal lavage fluid 1372:1398 the intestinal lavage fluid of the two groups 1372:1416 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. 36998438 3 56 theme DC 437:438 arg1 pathogenesis 421:432 the pathogenesis 417:432 the pathogenesis of DC 417:438 At present, no studies have analyzed the pathogenesis of DC from the perspective of the diversity and and differences of intestinal flora. 36998438 7 57 theme mild 1180:1183 arg1 group 1185:1189 mild group 1180:1189 mild group 1180:1189 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 13 58 dep Conclusion 2451:2460 arg1 surgery 2486:2492 ileostomy closure surgery 2468:2492 ileostomy closure surgery 2468:2492 Conclusion After ileostomy closure surgery, a series of severe clinical symptoms might appear in DC patients. 36998438 9 59 theme DC 1587:1588 arg1 severity 1590:1597 DC severity 1587:1597 DC severity (P<0.05) 1587:1606 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 59 theme DC 1587:1588 arg1 P<0.05 1600:1605 P<0.05 1600:1605 P<0.05 1600:1605 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 12 60 theme flora 2339:2343 arg1 types 2319:2323 such two types 2310:2323 such two types of intestinal flora 2310:2343 The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. 36998438 3 61 theme diversity 468:476 arg1 differences 486:496 and differences 482:496 differences 486:496 At present, no studies have analyzed the pathogenesis of DC from the perspective of the diversity and and differences of intestinal flora. 36998438 3 61 theme diversity 468:476 arg1 perspective 449:459 the perspective 445:459 the perspective of the diversity 445:476 At present, no studies have analyzed the pathogenesis of DC from the perspective of the diversity and and differences of intestinal flora. 36998438 10 62 theme mild 2009:2012 arg1 group 2014:2018 the mild group 2005:2018 the mild group 2005:2018 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 63 theme colonscopic 1654:1664 arg1 score 1666:1670 colonscopic score 1654:1670 colonscopic score 1654:1670 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 63 theme colonscopic 1654:1664 arg1 Meanwhile 1609:1617 Meanwhile 1609:1617 Meanwhile 1609:1617 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 1 64 theme mucosa 213:218 arg1 inflammation 175:186 nonspecific inflammation 163:186 nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction 163:286 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 1 65 with disruption 230:239 arg1 dysfunction 276:286 colonic dysfunction 268:286 colonic dysfunction 268:286 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 14 66 theme systemic 2608:2615 arg1 responses 2630:2638 local and systemic inflammatory responses 2598:2638 local and systemic inflammatory responses 2598:2638 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 11 67 theme mild 2199:2202 arg1 group 2204:2208 mild group 2199:2208 mild group 2199:2208 The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. 36998438 5 68 dep enterostomy 818:828 arg1 dual-chamber 831:842 dual-chamber 831:842 dual-chamber 831:842 These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). 36998438 10 69 theme independent 1689:1699 arg1 factors 1706:1712 independent risk factors 1689:1712 independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy 1689:1880 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 6 70 theme clinical 915:922 arg1 symptoms 924:931 clinical symptoms 915:931 clinical symptoms 915:931 We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. 36998438 0 71 dep Interaction 0:10 arg1 resection 98:106 low anterior resection 85:106 low anterior resection of rectal cancer 85:123 Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer. 36998438 14 72 theme local 2598:2602 arg1 responses 2630:2638 local and systemic inflammatory responses 2598:2638 local and systemic inflammatory responses 2598:2638 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 4 73 theme rectal 607:612 arg1 cancer 614:619 low rectal cancer 603:619 low rectal cancer 603:619 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 10 74 theme DC 1863:1864 arg1 severity 1851:1858 the severity 1847:1858 the severity of DC 1847:1864 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 1 75 theme colonic 244:250 arg1 continuity 252:261 colonic continuity 244:261 colonic continuity 244:261 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 12 76 from predictions 2295:2305 arg1 types 2319:2323 such two types 2310:2323 such two types of intestinal flora 2310:2343 The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. 36998438 12 77 theme functional 2284:2293 arg1 predictions 2295:2305 The functional predictions 2280:2305 The functional predictions on such two types of intestinal flora 2280:2343 The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. 36998438 13 78 theme closure 2478:2484 arg1 surgery 2486:2492 ileostomy closure surgery 2468:2492 ileostomy closure surgery 2468:2492 Conclusion After ileostomy closure surgery, a series of severe clinical symptoms might appear in DC patients. 36998438 2 79 theme colonscopic 293:303 arg1 tool 321:324 a good tool 314:324 a good tool for differentiating the severity of patients with DC 314:377 The colonscopic score is a good tool for differentiating the severity of patients with DC. 36998438 2 79 theme colonscopic 293:303 arg1 score 305:309 The colonscopic score 289:309 The colonscopic score 289:309 The colonscopic score is a good tool for differentiating the severity of patients with DC. 36998438 6 80 theme clinical 884:891 arg1 information 902:912 comparethe clinical baseline information 873:912 comparethe clinical baseline information 873:912 We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. 36998438 7 81 theme terminal 1115:1122 arg1 enterostomy 1130:1140 terminal ileum enterostomy 1115:1140 terminal ileum enterostomy 1115:1140 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 14 82 from DC 2796:2797 arg1 patients 2802:2809 patients 2802:2809 patients with permanent stoma 2802:2830 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 3 83 theme flora 512:516 arg1 differences 486:496 and differences 482:496 differences 486:496 At present, no studies have analyzed the pathogenesis of DC from the perspective of the diversity and and differences of intestinal flora. 36998438 3 83 theme flora 512:516 arg1 perspective 449:459 the perspective 445:459 the perspective of the diversity 445:476 At present, no studies have analyzed the pathogenesis of DC from the perspective of the diversity and and differences of intestinal flora. 36998438 11 84 theme 16s-rDNA 2063:2070 arg1 sequencing 2072:2081 16s-rDNA sequencing 2063:2081 16s-rDNA sequencing 2063:2081 The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. 36998438 10 85 theme severe 2034:2039 arg1 group 2041:2045 the severe group 2030:2045 the severe group 2030:2045 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 5 86 theme anterior 764:771 arg1 LAR 784:786 LAR 784:786 LAR 784:786 These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). 36998438 5 86 theme anterior 764:771 arg1 resection 773:781 laparoscopic low anterior resection 747:781 laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber) 747:843 These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). 36998438 7 87 theme colonscopic 1235:1245 arg1 examinations 1247:1258 colonscopic examinations 1235:1258 colonscopic examinations for DC 1235:1265 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 2 88 theme good 316:319 arg1 tool 321:324 a good tool 314:324 a good tool for differentiating the severity of patients with DC 314:377 The colonscopic score is a good tool for differentiating the severity of patients with DC. 36998438 2 88 theme good 316:319 arg1 score 305:309 The colonscopic score 289:309 The colonscopic score 289:309 The colonscopic score is a good tool for differentiating the severity of patients with DC. 36998438 1 89 theme nonspecific 163:173 arg1 inflammation 175:186 nonspecific inflammation 163:186 nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction 163:286 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 14 90 theme significant 2571:2581 arg1 differences 2583:2593 significant differences 2571:2593 significant differences 2571:2593 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 14 91 theme clinical 2758:2765 arg1 treatment 2782:2790 the clinical interventional treatment 2754:2790 the clinical interventional treatment for DC in patients with permanent stoma 2754:2830 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 4 92 theme Surgery 661:667 arg1 Department 637:646 the Department 633:646 the Department of Anorectal Surgery, Changzheng Hospital 633:688 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 0 93 theme cancer 118:123 arg1 resection 98:106 low anterior resection 85:106 low anterior resection of rectal cancer 85:123 Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer. 36998438 10 94 theme oberservational 1898:1912 arg1 study 1914:1918 propsective oberservational study 1886:1918 propsective oberservational study 1886:1918 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 94 theme oberservational 1898:1912 arg1 patients 1924:1931 40 patients 1921:1931 40 patients with low rectal cancer recruited by sample size calculation 1921:1991 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 7 95 theme laparoscopic 1065:1076 arg1 resection 1091:1099 laparoscopic anterior low resection 1065:1099 laparoscopic anterior low resection combined with terminal ileum enterostomy 1065:1140 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 8 96 theme 16s-rDNA 1268:1275 arg1 sequencing 1277:1286 16s-rDNA sequencing 1268:1286 16s-rDNA sequencing 1268:1286 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. 36998438 1 97 theme distal 195:200 arg1 mucosa 213:218 the distal intestinal mucosa 191:218 the distal intestinal mucosa 191:218 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 6 98 theme colonscopic 938:948 arg1 characteristics 950:964 colonscopic characteristics 938:964 colonscopic characteristics 938:964 We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. 36998438 10 99 theme low 1938:1940 arg1 cancer 1949:1954 low rectal cancer 1938:1954 low rectal cancer 1938:1954 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 100 theme closure 1765:1771 arg1 surgery 1773:1779 ileostomy closure surgery 1755:1779 ileostomy closure surgery(P<0.05) 1755:1787 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 10 100 theme closure 1765:1771 arg1 P<0.05 1781:1786 P<0.05 1781:1786 P<0.05 1781:1786 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 7 101 theme low 1087:1089 arg1 resection 1091:1099 laparoscopic anterior low resection 1065:1099 laparoscopic anterior low resection combined with terminal ileum enterostomy 1065:1140 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 4 102 with patients 589:596 arg1 cancer 614:619 low rectal cancer 603:619 low rectal cancer 603:619 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 10 103 with patients 1924:1931 arg1 cancer 1949:1954 low rectal cancer 1938:1954 low rectal cancer 1938:1954 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 12 104 theme glycan 2385:2390 arg1 synthesis 2392:2400 glycan synthesis 2385:2400 glycan synthesis 2385:2400 The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. 36998438 7 105 theme examinations 1247:1258 arg1 scores 1225:1230 the scores 1221:1230 the scores of colonscopic examinations for DC 1221:1265 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 7 106 theme Propsective 1000:1010 arg1 study 1028:1032 Propsective oberservational study 1000:1032 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 1000:1266 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 1 107 theme Diversion 137:145 arg1 colitis 147:153 Background Diversion colitis 126:153 Background Diversion colitis (DC) 126:158 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 1 107 theme Diversion 137:145 arg1 DC 156:157 DC 156:157 DC 156:157 Background Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. 36998438 14 108 theme different 2698:2706 arg1 scores 2720:2725 different colonscopic scores 2698:2725 different colonscopic scores 2698:2725 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 5 109 theme low 760:762 arg1 LAR 784:786 LAR 784:786 LAR 784:786 These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). 36998438 5 109 theme low 760:762 arg1 resection 773:781 laparoscopic low anterior resection 747:781 laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber) 747:843 These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). 36998438 4 110 dep Methods 519:525 arg1 collected 574:582 collected 574:582 collected 574:582 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 4 110 dep Methods 519:525 arg1 study 541:545 Retrospective study 527:545 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 519:720 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 0 111 theme anterior 89:96 arg1 resection 98:106 low anterior resection 85:106 low anterior resection of rectal cancer 85:123 Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer. 36998438 8 112 from diversity 1319:1327 arg1 fluid 1394:1398 the intestinal lavage fluid 1372:1398 the intestinal lavage fluid of the two groups 1372:1416 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. 36998438 9 113 theme stoma 1529:1533 arg1 state 1535:1539 the stoma state 1525:1539 the stoma state 1525:1539 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 6 114 theme DC 996:997 arg1 severity 984:991 different severity 974:991 different severity of DC 974:997 We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. 36998438 8 115 theme flora 1363:1367 arg1 diversity 1319:1327 the diversity 1315:1327 the diversity 1315:1327 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. 36998438 8 115 theme flora 1363:1367 arg1 differences 1337:1347 and differences 1333:1347 differences 1337:1347 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. 36998438 10 116 theme size 1976:1979 arg1 calculation 1981:1991 sample size calculation 1969:1991 sample size calculation 1969:1991 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 13 117 theme DC 2548:2549 arg1 patients 2551:2558 DC patients 2548:2558 DC patients 2548:2558 Conclusion After ileostomy closure surgery, a series of severe clinical symptoms might appear in DC patients. 36998438 7 118 theme severe 1195:1200 arg1 group 1202:1206 severe group 1195:1206 severe group 1195:1206 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 14 119 with patients 2802:2809 arg1 stoma 2826:2830 permanent stoma 2816:2830 permanent stoma 2816:2830 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 9 120 theme independent 1550:1560 arg1 BMI 1470:1472 BMI 1470:1472 BMI 1470:1472 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 120 theme independent 1550:1560 arg1 age 1465:1467 age 1465:1467 age 1465:1467 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 120 theme independent 1550:1560 arg1 factors 1567:1573 the independent risk factors 1546:1573 the independent risk factors that affect DC severity (P<0.05) 1546:1606 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 120 theme independent 1550:1560 arg1 symptoms 1500:1507 symptoms 1500:1507 symptoms associated with the stoma state 1500:1539 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 9 120 theme independent 1550:1560 arg1 history 1475:1481 history 1475:1481 history of diabetes 1475:1493 Results In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). 36998438 7 121 with patients 1051:1058 arg1 resection 1091:1099 laparoscopic anterior low resection 1065:1099 laparoscopic anterior low resection combined with terminal ileum enterostomy 1065:1140 Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 36998438 11 122 theme intestinal 2095:2104 arg1 flora 2106:2110 intestinal flora 2095:2110 intestinal flora with high enrichment values 2095:2138 The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. 36998438 12 123 theme lipid 2368:2372 arg1 synthesis 2374:2382 lipid synthesis 2368:2382 lipid synthesis 2368:2382 The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. 36998438 8 124 theme lavage 1387:1392 arg1 fluid 1394:1398 the intestinal lavage fluid 1372:1398 the intestinal lavage fluid of the two groups 1372:1416 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. 36998438 0 125 theme intestinal 24:33 arg1 flora 35:39 the intestinal flora 20:39 the intestinal flora 20:39 Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer. 36998438 14 126 theme flora 2667:2671 arg1 composition 2641:2651 composition 2641:2651 composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma 2641:2830 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 11 127 theme enrichment 2122:2131 arg1 values 2133:2138 high enrichment values 2117:2138 high enrichment values 2117:2138 The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. 36998438 6 128 used used 849:852 arg2 We 846:847 We 846:847 We 846:847 We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. 36998438 10 129 with consistent 1800:1809 arg1 results 1820:1826 our results 1816:1826 our results of differentiating the severity of DC under endoscopy 1816:1880 Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. 36998438 4 130 theme Retrospective 527:539 arg1 study 541:545 Retrospective study 527:545 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 519:720 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 13 131 theme symptoms 2523:2530 arg1 series 2497:2502 a series 2495:2502 a series of severe clinical symptoms 2495:2530 Conclusion After ileostomy closure surgery, a series of severe clinical symptoms might appear in DC patients. 36998438 14 132 theme inflammatory 2617:2628 arg1 responses 2630:2638 local and systemic inflammatory responses 2598:2638 local and systemic inflammatory responses 2598:2638 There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma. 36998438 4 133 theme low 603:605 arg1 cancer 614:619 low rectal cancer 603:619 low rectal cancer 603:619 Methods Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. 36998438 2 134 theme patients 362:369 arg1 severity 350:357 the severity 346:357 the severity of patients with DC 346:377 The colonscopic score is a good tool for differentiating the severity of patients with DC. 36998438 2 135 with patients 362:369 arg1 DC 376:377 DC 376:377 DC 376:377 The colonscopic score is a good tool for differentiating the severity of patients with DC. 36998438 12 136 theme intestinal 2328:2337 arg1 flora 2339:2343 intestinal flora 2328:2343 intestinal flora 2328:2343 The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. 36998438 3 137 theme intestinal 501:510 arg1 flora 512:516 intestinal flora 501:516 intestinal flora 501:516 At present, no studies have analyzed the pathogenesis of DC from the perspective of the diversity and and differences of intestinal flora. 37237464 9 0 theme potential 1846:1854 arg1 risk 1856:1859 a potential risk 1844:1859 a potential risk for intestinal health 1844:1881 Meanwhile, the upregulation of the KEGG pathway of lipopolysaccharide biosynthesis indicates a potential risk for intestinal health. 37237464 8 1 theme acid 1647:1650 arg1 pathways 1629:1636 the KEGG pathways 1620:1636 the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism 1620:1719 The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. 37237464 1 2 theme alternate 264:272 arg1 feeding 274:280 alternate feeding 264:280 alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets 264:351 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 10 3 theme negative 2059:2066 arg1 effects 2068:2074 both positive and negative effects 2041:2074 both positive and negative effects 2041:2074 In conclusion, short-term alternate feeding between dietary lipid sources reshapes the intestinal microecology of the juvenile turbot, possibly resulting in both positive and negative effects. 37237464 10 4 theme alternate 1910:1918 arg1 feeding 1920:1926 short-term alternate feeding 1899:1926 short-term alternate feeding between dietary lipid sources 1899:1956 In conclusion, short-term alternate feeding between dietary lipid sources reshapes the intestinal microecology of the juvenile turbot, possibly resulting in both positive and negative effects. 37237464 6 5 theme specific 1169:1176 arg1 acid 1222:1225 short-chain fatty acid 1204:1225 short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium) 1204:1373 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 5 theme specific 1169:1176 arg1 microorganisms 1178:1191 selectively enriched specific microorganisms 1148:1191 selectively enriched specific microorganisms 1148:1191 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 8 6 theme lipid 1656:1660 arg1 metabolism 1662:1671 lipid metabolism 1656:1671 lipid metabolism 1656:1671 The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. 37237464 2 7 dep feeding 487:493 arg1 2 467:467 2 467:467 2 467:467 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 7 8 theme Alternate 1376:1384 arg1 feeding 1386:1392 Alternate feeding 1376:1392 Alternate feeding 1376:1392 Alternate feeding may maintain the intestinal microbiota balance by improving the connectivity of the ecological network and increasing the competitive interactions within the ecological network. 37237464 2 9 theme SO/FO 541:545 arg1 diets 534:538 FO-based diets 525:538 FO-based diets (SO/FO group) 525:552 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 9 theme SO/FO 541:545 arg1 group 547:551 SO/FO group 541:551 SO/FO group 541:551 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 10 theme FO-based 618:625 arg1 diets 627:631 FO-based diets 618:631 FO-based diets (BT/FO group) 618:645 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 10 theme FO-based 618:625 arg1 group 640:644 BT/FO group 634:644 BT/FO group 634:644 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 10 11 theme lipid 1944:1948 arg1 sources 1950:1956 dietary lipid sources 1936:1956 dietary lipid sources 1936:1956 In conclusion, short-term alternate feeding between dietary lipid sources reshapes the intestinal microecology of the juvenile turbot, possibly resulting in both positive and negative effects. 37237464 6 12 theme Mycoplasma 1133:1142 arg1 abundance 1120:1128 the abundance 1116:1128 the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium) 1116:1373 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 0 13 theme Juvenile 130:137 arg1 Turbot 139:144 Juvenile Turbot 130:144 Juvenile Turbot 130:144 Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets Modulates the Intestinal Microecology of Juvenile Turbot. 37237464 5 14 theme feeding 960:966 arg1 strategy 968:975 the feeding strategy 956:975 the feeding strategy 956:975 A PCoA analysis showed that the samples clustered separately according to the feeding strategy, and among the three groups, the SO/FO group clustered relatively closer to the BT/FO group. 37237464 4 15 theme intestinal 813:822 arg1 microbiota 824:833 the intestinal microbiota 809:833 the intestinal microbiota 809:833 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 10 16 theme intestinal 1971:1980 arg1 microecology 1982:1993 the intestinal microecology 1967:1993 the intestinal microecology of the juvenile turbot 1967:2016 In conclusion, short-term alternate feeding between dietary lipid sources reshapes the intestinal microecology of the juvenile turbot, possibly resulting in both positive and negative effects. 37237464 8 17 theme acid 1705:1708 arg1 metabolism 1710:1719 amino acid metabolism 1699:1719 amino acid metabolism 1699:1719 The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. 37237464 5 18 theme BT/FO 1057:1061 arg1 group 1063:1067 the BT/FO group 1053:1067 the BT/FO group 1053:1067 A PCoA analysis showed that the samples clustered separately according to the feeding strategy, and among the three groups, the SO/FO group clustered relatively closer to the BT/FO group. 37237464 2 19 theme soybean 503:509 arg1 oil 511:513 soybean oil 503:513 soybean oil (SO)- 503:519 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 20 theme alternate 570:578 arg1 feeding 580:586 (3) weekly alternate feeding 559:586 (3) weekly alternate feeding 559:586 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 3 21 theme intestinal 651:660 arg1 analysis 682:689 An intestinal bacterial community analysis 648:689 An intestinal bacterial community analysis 648:689 An intestinal bacterial community analysis showed that alternate feeding reshaped the intestinal microbial composition. 37237464 6 22 theme short-chain 1204:1214 arg1 acid 1222:1225 short-chain fatty acid 1204:1225 short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium) 1204:1373 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 22 theme short-chain 1204:1214 arg1 SCFA 1228:1231 SCFA 1228:1231 SCFA 1228:1231 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 8 23 theme intestinal 1728:1737 arg1 microbiota 1739:1748 the intestinal microbiota 1724:1748 the intestinal microbiota 1724:1748 The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. 37237464 3 24 theme alternate 703:711 arg1 feeding 713:719 alternate feeding 703:719 alternate feeding 703:719 An intestinal bacterial community analysis showed that alternate feeding reshaped the intestinal microbial composition. 37237464 4 25 theme alternate-feeding 856:872 arg1 groups 874:879 the alternate-feeding groups 852:879 the alternate-feeding groups 852:879 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 6 26 theme alternate 1074:1082 arg1 feeding 1084:1090 The alternate feeding 1070:1090 The alternate feeding 1070:1090 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 1 27 theme fish 327:330 arg1 oil 332:334 fish oil 327:334 fish oil 327:334 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 1 28 theme feeding 159:165 arg1 trial 167:171 A nine-week feeding trial 147:171 A nine-week feeding trial 147:171 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 5 29 theme SO/FO 1010:1014 arg1 group 1016:1020 the SO/FO group 1006:1020 the SO/FO group 1006:1020 A PCoA analysis showed that the samples clustered separately according to the feeding strategy, and among the three groups, the SO/FO group clustered relatively closer to the BT/FO group. 37237464 2 30 dep feeding 423:429 arg1 1 409:409 1 409:409 1 409:409 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 3 31 theme intestinal 734:743 arg1 composition 755:765 the intestinal microbial composition 730:765 the intestinal microbial composition 730:765 An intestinal bacterial community analysis showed that alternate feeding reshaped the intestinal microbial composition. 37237464 3 32 theme community 672:680 arg1 analysis 682:689 An intestinal bacterial community analysis 648:689 An intestinal bacterial community analysis 648:689 An intestinal bacterial community analysis showed that alternate feeding reshaped the intestinal microbial composition. 37237464 6 33 dep bacteria 1264:1271 arg1 bacteria 1264:1271 digestive bacteria 1254:1271 digestive bacteria (Corynebacterium and Sphingomonas) 1254:1306 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 33 dep bacteria 1264:1271 arg1 Sphingomonas 1294:1305 Sphingomonas 1294:1305 Sphingomonas 1294:1305 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 33 dep bacteria 1264:1271 arg1 Corynebacterium 1274:1288 Corynebacterium 1274:1288 Corynebacterium 1274:1288 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 7 34 theme ecological 1478:1487 arg1 network 1489:1495 the ecological network 1474:1495 the ecological network 1474:1495 Alternate feeding may maintain the intestinal microbiota balance by improving the connectivity of the ecological network and increasing the competitive interactions within the ecological network. 37237464 2 35 theme feeding 374:380 arg1 strategies 382:391 The following three feeding strategies 354:391 The following three feeding strategies 354:391 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 0 36 theme Sourced 51:57 arg1 Oil- 59:62 Terrestrially Sourced Oil- 37:62 Terrestrially Sourced Oil- 37:62 Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets Modulates the Intestinal Microecology of Juvenile Turbot. 37237464 2 37 theme continuous 412:421 arg1 feeding 423:429 (1) continuous feeding 408:429 (1) continuous feeding with the FO-based diet (FO group) 408:463 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 38 theme following 358:366 arg1 strategies 382:391 The following three feeding strategies 354:391 The following three feeding strategies 354:391 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 0 39 theme Short-Term 0:9 arg1 Feeding 21:27 Short-Term Alternate Feeding 0:27 Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets 0:87 Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets Modulates the Intestinal Microecology of Juvenile Turbot. 37237464 10 40 theme juvenile 2002:2009 arg1 turbot 2011:2016 the juvenile turbot 1998:2016 the juvenile turbot 1998:2016 In conclusion, short-term alternate feeding between dietary lipid sources reshapes the intestinal microecology of the juvenile turbot, possibly resulting in both positive and negative effects. 37237464 2 41 dep feeding 580:586 arg1 3 560:560 3 560:560 3 560:560 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 1 42 from changes 202:208 arg1 response 252:259 response 252:259 response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets 252:351 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 1 42 from changes 202:208 arg1 microbiota 228:237 the intestinal microbiota 213:237 the intestinal microbiota of turbot 213:247 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 2 43 theme FO-based 440:447 arg1 diet 449:452 the FO-based diet 436:452 the FO-based diet (FO group) 436:463 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 43 theme FO-based 440:447 arg1 group 458:462 FO group 455:462 FO group 455:462 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 6 44 theme several 1313:1319 arg1 Mycobacterium 1360:1372 Mycobacterium 1360:1372 Mycobacterium 1360:1372 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 44 theme several 1313:1319 arg1 Desulfovibrio 1342:1354 Desulfovibrio 1342:1354 Desulfovibrio 1342:1354 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 44 theme several 1313:1319 arg1 pathogens 1331:1339 several potential pathogens 1313:1339 several potential pathogens (Desulfovibrio and Mycobacterium) 1313:1373 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 0 45 dep Oil- 59:62 arg1 Diets 83:87 Oil-Based Diets 73:87 Oil-Based Diets 73:87 Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets Modulates the Intestinal Microecology of Juvenile Turbot. 37237464 9 46 theme KEGG 1786:1789 arg1 pathway 1791:1797 the KEGG pathway 1782:1797 the KEGG pathway of lipopolysaccharide biosynthesis 1782:1832 Meanwhile, the upregulation of the KEGG pathway of lipopolysaccharide biosynthesis indicates a potential risk for intestinal health. 37237464 6 47 dep pathogens 1331:1339 arg1 Mycobacterium 1360:1372 Mycobacterium 1360:1372 Mycobacterium 1360:1372 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 47 dep pathogens 1331:1339 arg1 Desulfovibrio 1342:1354 Desulfovibrio 1342:1354 Desulfovibrio 1342:1354 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 47 dep pathogens 1331:1339 arg1 pathogens 1331:1339 several potential pathogens 1313:1339 several potential pathogens (Desulfovibrio and Mycobacterium) 1313:1373 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 1 48 dep -based 340:345 arg1 oil 312:314 terrestrially sourced oil 290:314 terrestrially sourced oil 290:314 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 1 48 dep -based 340:345 arg1 oil 332:334 fish oil 327:334 fish oil 327:334 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 1 48 dep -based 340:345 arg1 TSO 317:319 TSO 317:319 TSO 317:319 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 7 49 theme intestinal 1411:1420 arg1 balance 1433:1439 the intestinal microbiota balance 1407:1439 the intestinal microbiota balance 1407:1439 Alternate feeding may maintain the intestinal microbiota balance by improving the connectivity of the ecological network and increasing the competitive interactions within the ecological network. 37237464 5 50 theme PCoA 884:887 arg1 analysis 889:896 A PCoA analysis 882:896 A PCoA analysis 882:896 A PCoA analysis showed that the samples clustered separately according to the feeding strategy, and among the three groups, the SO/FO group clustered relatively closer to the BT/FO group. 37237464 9 51 theme biosynthesis 1821:1832 arg1 pathway 1791:1797 the KEGG pathway 1782:1797 the KEGG pathway of lipopolysaccharide biosynthesis 1782:1832 Meanwhile, the upregulation of the KEGG pathway of lipopolysaccharide biosynthesis indicates a potential risk for intestinal health. 37237464 2 52 dep oil 511:513 arg1 SO 516:517 SO 516:517 SO 516:517 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 6 53 theme microorganisms 1178:1191 arg1 abundance 1120:1128 the abundance 1116:1128 the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium) 1116:1373 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 8 54 theme fatty 1641:1645 arg1 acid 1647:1650 fatty acid 1641:1650 fatty acid 1641:1650 The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. 37237464 9 55 theme intestinal 1865:1874 arg1 health 1876:1881 intestinal health 1865:1881 intestinal health 1865:1881 Meanwhile, the upregulation of the KEGG pathway of lipopolysaccharide biosynthesis indicates a potential risk for intestinal health. 37237464 8 56 theme alternate 1576:1584 arg1 feeding 1586:1592 The alternate feeding 1572:1592 The alternate feeding 1572:1592 The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. 37237464 10 57 theme short-term 1899:1908 arg1 feeding 1920:1926 short-term alternate feeding 1899:1926 short-term alternate feeding between dietary lipid sources 1899:1956 In conclusion, short-term alternate feeding between dietary lipid sources reshapes the intestinal microecology of the juvenile turbot, possibly resulting in both positive and negative effects. 37237464 6 58 theme enriched 1160:1167 arg1 acid 1222:1225 short-chain fatty acid 1204:1225 short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium) 1204:1373 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 58 theme enriched 1160:1167 arg1 microorganisms 1178:1191 selectively enriched specific microorganisms 1148:1191 selectively enriched specific microorganisms 1148:1191 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 8 59 theme metabolism 1662:1671 arg1 pathways 1629:1636 the KEGG pathways 1620:1636 the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism 1620:1719 The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. 37237464 2 60 theme FO-based 525:532 arg1 diets 534:538 FO-based diets 525:538 FO-based diets (SO/FO group) 525:552 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 60 theme FO-based 525:532 arg1 group 547:551 SO/FO group 541:551 SO/FO group 541:551 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 10 61 theme dietary 1936:1942 arg1 sources 1950:1956 dietary lipid sources 1936:1956 dietary lipid sources 1936:1956 In conclusion, short-term alternate feeding between dietary lipid sources reshapes the intestinal microecology of the juvenile turbot, possibly resulting in both positive and negative effects. 37237464 0 62 theme Turbot 139:144 arg1 Microecology 114:125 the Intestinal Microecology 99:125 the Intestinal Microecology of Juvenile Turbot 99:144 Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets Modulates the Intestinal Microecology of Juvenile Turbot. 37237464 8 63 theme glycan 1674:1679 arg1 biosynthesis 1681:1692 glycan biosynthesis 1674:1692 glycan biosynthesis 1674:1692 The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. 37237464 2 64 theme alternate 477:485 arg1 feeding 487:493 alternate feeding 477:493 (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group) 466:552 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 65 theme BT/FO 634:638 arg1 diets 627:631 FO-based diets 618:631 FO-based diets (BT/FO group) 618:645 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 65 theme BT/FO 634:638 arg1 group 640:644 BT/FO group 634:644 BT/FO group 634:644 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 1 66 theme intestinal 217:226 arg1 microbiota 228:237 the intestinal microbiota 213:237 the intestinal microbiota of turbot 213:247 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 7 67 theme ecological 1552:1561 arg1 network 1563:1569 the ecological network 1548:1569 the ecological network 1548:1569 Alternate feeding may maintain the intestinal microbiota balance by improving the connectivity of the ecological network and increasing the competitive interactions within the ecological network. 37237464 2 68 theme beef 596:599 arg1 BT 609:610 BT 609:610 BT 609:610 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 68 theme beef 596:599 arg1 tallow 601:606 beef tallow 596:606 beef tallow (BT)- 596:612 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 8 69 theme amino 1699:1703 arg1 metabolism 1710:1719 amino acid metabolism 1699:1719 amino acid metabolism 1699:1719 The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. 37237464 4 70 theme Higher 768:773 arg1 richness 783:790 richness 783:790 richness 783:790 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 4 70 theme Higher 768:773 arg1 species 775:781 Higher species richness and diversity 768:804 Higher species richness and diversity of the intestinal microbiota 768:833 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 4 70 theme Higher 768:773 arg1 diversity 796:804 diversity 796:804 diversity 796:804 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 6 71 theme fatty 1216:1220 arg1 acid 1222:1225 short-chain fatty acid 1204:1225 short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium) 1204:1373 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 71 theme fatty 1216:1220 arg1 SCFA 1228:1231 SCFA 1228:1231 SCFA 1228:1231 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 7 72 theme competitive 1516:1526 arg1 interactions 1528:1539 the competitive interactions 1512:1539 the competitive interactions within the ecological network 1512:1569 Alternate feeding may maintain the intestinal microbiota balance by improving the connectivity of the ecological network and increasing the competitive interactions within the ecological network. 37237464 3 73 theme bacterial 662:670 arg1 analysis 682:689 An intestinal bacterial community analysis 648:689 An intestinal bacterial community analysis 648:689 An intestinal bacterial community analysis showed that alternate feeding reshaped the intestinal microbial composition. 37237464 0 74 theme Oil-Based 73:81 arg1 Diets 83:87 Oil-Based Diets 73:87 Oil-Based Diets 73:87 Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets Modulates the Intestinal Microecology of Juvenile Turbot. 37237464 2 75 with feeding 423:429 arg1 diet 449:452 the FO-based diet 436:452 the FO-based diet (FO group) 436:463 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 75 with feeding 423:429 arg1 group 458:462 FO group 455:462 FO group 455:462 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 1 76 theme nine-week 149:157 arg1 trial 167:171 A nine-week feeding trial 147:171 A nine-week feeding trial 147:171 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 10 77 theme positive 2046:2053 arg1 effects 2068:2074 both positive and negative effects 2041:2074 both positive and negative effects 2041:2074 In conclusion, short-term alternate feeding between dietary lipid sources reshapes the intestinal microecology of the juvenile turbot, possibly resulting in both positive and negative effects. 37237464 2 78 theme FO 455:456 arg1 diet 449:452 the FO-based diet 436:452 the FO-based diet (FO group) 436:463 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 78 theme FO 455:456 arg1 group 458:462 FO group 455:462 FO group 455:462 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 4 79 located observed 840:847 arg1 groups 874:879 the alternate-feeding groups 852:879 the alternate-feeding groups 852:879 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 4 79 located observed 840:847 arg2 diversity 796:804 diversity 796:804 diversity 796:804 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 4 79 located observed 840:847 arg2 species 775:781 Higher species richness and diversity 768:804 Higher species richness and diversity of the intestinal microbiota 768:833 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 4 79 located observed 840:847 arg2 richness 783:790 richness 783:790 richness 783:790 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 4 80 dep species 775:781 arg1 richness 783:790 richness 783:790 richness 783:790 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 4 80 dep species 775:781 arg1 species 775:781 Higher species richness and diversity 768:804 Higher species richness and diversity of the intestinal microbiota 768:833 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 4 80 dep species 775:781 arg1 diversity 796:804 diversity 796:804 diversity 796:804 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 7 81 theme network 1489:1495 arg1 connectivity 1458:1469 the connectivity 1454:1469 the connectivity of the ecological network 1454:1495 Alternate feeding may maintain the intestinal microbiota balance by improving the connectivity of the ecological network and increasing the competitive interactions within the ecological network. 37237464 0 82 theme Intestinal 103:112 arg1 Microecology 114:125 the Intestinal Microecology 99:125 the Intestinal Microecology of Juvenile Turbot 99:144 Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets Modulates the Intestinal Microecology of Juvenile Turbot. 37237464 3 83 theme microbial 745:753 arg1 composition 755:765 the intestinal microbial composition 730:765 the intestinal microbial composition 730:765 An intestinal bacterial community analysis showed that alternate feeding reshaped the intestinal microbial composition. 37237464 4 84 theme microbiota 824:833 arg1 richness 783:790 richness 783:790 richness 783:790 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 4 84 theme microbiota 824:833 arg1 species 775:781 Higher species richness and diversity 768:804 Higher species richness and diversity of the intestinal microbiota 768:833 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 4 84 theme microbiota 824:833 arg1 diversity 796:804 diversity 796:804 diversity 796:804 Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. 37237464 10 85 theme turbot 2011:2016 arg1 microecology 1982:1993 the intestinal microecology 1967:1993 the intestinal microecology of the juvenile turbot 1967:2016 In conclusion, short-term alternate feeding between dietary lipid sources reshapes the intestinal microecology of the juvenile turbot, possibly resulting in both positive and negative effects. 37237464 6 86 theme digestive 1254:1262 arg1 bacteria 1264:1271 digestive bacteria 1254:1271 digestive bacteria (Corynebacterium and Sphingomonas) 1254:1306 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 86 theme digestive 1254:1262 arg1 Sphingomonas 1294:1305 Sphingomonas 1294:1305 Sphingomonas 1294:1305 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 86 theme digestive 1254:1262 arg1 Corynebacterium 1274:1288 Corynebacterium 1274:1288 Corynebacterium 1274:1288 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 1 87 theme -based 340:345 arg1 diets 347:351 terrestrially sourced oil (TSO)- and fish oil (FO)-based diets 290:351 terrestrially sourced oil (TSO)- and fish oil (FO)-based diets 290:351 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 2 88 with feeding 487:493 arg1 diet 449:452 the FO-based diet 436:452 the FO-based diet (FO group) 436:463 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 88 with feeding 487:493 arg1 group 458:462 FO group 455:462 FO group 455:462 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 89 theme weekly 563:568 arg1 feeding 580:586 (3) weekly alternate feeding 559:586 (3) weekly alternate feeding 559:586 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 90 with feeding 580:586 arg1 diet 449:452 the FO-based diet 436:452 the FO-based diet (FO group) 436:463 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 90 with feeding 580:586 arg1 group 458:462 FO group 455:462 FO group 455:462 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 2 91 theme weekly 470:475 arg1 feeding 487:493 alternate feeding 477:493 (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group) 466:552 The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). 37237464 1 92 theme sourced 304:310 arg1 oil 312:314 terrestrially sourced oil 290:314 terrestrially sourced oil 290:314 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 1 92 theme sourced 304:310 arg1 TSO 317:319 TSO 317:319 TSO 317:319 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 6 93 theme potential 1321:1329 arg1 Mycobacterium 1360:1372 Mycobacterium 1360:1372 Mycobacterium 1360:1372 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 93 theme potential 1321:1329 arg1 Desulfovibrio 1342:1354 Desulfovibrio 1342:1354 Desulfovibrio 1342:1354 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 6 93 theme potential 1321:1329 arg1 pathogens 1331:1339 several potential pathogens 1313:1339 several potential pathogens (Desulfovibrio and Mycobacterium) 1313:1373 The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). 37237464 9 94 theme pathway 1791:1797 arg1 Meanwhile 1751:1759 Meanwhile 1751:1759 Meanwhile 1751:1759 Meanwhile, the upregulation of the KEGG pathway of lipopolysaccharide biosynthesis indicates a potential risk for intestinal health. 37237464 9 94 theme pathway 1791:1797 arg1 upregulation 1766:1777 the upregulation 1762:1777 the upregulation of the KEGG pathway of lipopolysaccharide biosynthesis 1762:1832 Meanwhile, the upregulation of the KEGG pathway of lipopolysaccharide biosynthesis indicates a potential risk for intestinal health. 37237464 9 95 theme lipopolysaccharide 1802:1819 arg1 biosynthesis 1821:1832 lipopolysaccharide biosynthesis 1802:1832 lipopolysaccharide biosynthesis 1802:1832 Meanwhile, the upregulation of the KEGG pathway of lipopolysaccharide biosynthesis indicates a potential risk for intestinal health. 37237464 8 96 theme KEGG 1624:1627 arg1 pathways 1629:1636 the KEGG pathways 1620:1636 the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism 1620:1719 The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. 37237464 1 97 theme turbot 242:247 arg1 microbiota 228:237 the intestinal microbiota 213:237 the intestinal microbiota of turbot 213:247 A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. 37237464 7 98 theme microbiota 1422:1431 arg1 balance 1433:1439 the intestinal microbiota balance 1407:1439 the intestinal microbiota balance 1407:1439 Alternate feeding may maintain the intestinal microbiota balance by improving the connectivity of the ecological network and increasing the competitive interactions within the ecological network. 37237464 0 99 theme Alternate 11:19 arg1 Feeding 21:27 Short-Term Alternate Feeding 0:27 Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets 0:87 Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets Modulates the Intestinal Microecology of Juvenile Turbot. 36944617 1 0 theme host-specific 324:336 arg1 factors 338:344 host-specific factors 324:344 host-specific factors 324:344 The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. 36944617 1 1 theme diverse 153:159 arg1 bacteria 161:168 diverse bacteria 153:168 diverse bacteria from the diet 153:182 The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. 36944617 4 2 from commensals 1001:1010 arg1 genus 1031:1035 the Acetobacter genus 1015:1035 the Acetobacter genus 1015:1035 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 0 3 theme gut 102:104 arg1 microbiota 106:115 a multi-species gut microbiota 86:115 a multi-species gut microbiota 86:115 A symbiotic physical niche in Drosophila melanogaster regulates stable association of a multi-species gut microbiota. 36944617 4 4 theme secondary 789:797 arg1 colonizers 799:808 secondary colonizers 789:808 secondary colonizers of the same strain 789:827 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 0 5 theme multi-species 88:100 arg1 microbiota 106:115 a multi-species gut microbiota 86:115 a multi-species gut microbiota 86:115 A symbiotic physical niche in Drosophila melanogaster regulates stable association of a multi-species gut microbiota. 36944617 5 6 theme microbiome 1162:1171 arg1 stability 1122:1130 stability 1122:1130 stability 1122:1130 Our results provide a mechanistic framework for understanding the establishment and stability of a multi-species intestinal microbiome. 36944617 5 6 theme microbiome 1162:1171 arg1 establishment 1104:1116 establishment 1104:1116 establishment 1104:1116 Our results provide a mechanistic framework for understanding the establishment and stability of a multi-species intestinal microbiome. 36944617 2 7 used used 432:435 arg2 we 429:430 we 429:430 we 429:430 To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. 36944617 3 8 with bacteria 667:674 arg1 specificity 694:704 strain-level specificity 681:704 strain-level specificity 681:704 We show that a host-constructed physical niche in the foregut selectively binds bacteria with strain-level specificity, stabilizing their colonization. 36944617 0 9 theme microbiota 106:115 arg1 association 71:81 stable association 64:81 stable association of a multi-species gut microbiota 64:115 A symbiotic physical niche in Drosophila melanogaster regulates stable association of a multi-species gut microbiota. 36944617 1 10 theme key 371:373 arg1 species 375:381 key species 371:381 key species of bacteria 371:393 The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. 36944617 4 11 theme Lactobacillus 858:870 arg1 species 872:878 Lactobacillus species 858:878 Lactobacillus species 858:878 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 0 12 theme symbiotic 2:10 arg1 niche 21:25 A symbiotic physical niche 0:25 A symbiotic physical niche in Drosophila melanogaster 0:52 A symbiotic physical niche in Drosophila melanogaster regulates stable association of a multi-species gut microbiota. 36944617 3 13 from niche 628:632 arg1 foregut 641:647 the foregut 637:647 the foregut 637:647 We show that a host-constructed physical niche in the foregut selectively binds bacteria with strain-level specificity, stabilizing their colonization. 36944617 2 14 theme gnotobiotic 437:447 arg1 Drosophila 449:458 gnotobiotic Drosophila 437:458 gnotobiotic Drosophila 437:458 To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. 36944617 1 15 theme host 267:270 arg1 species 272:278 host species 267:278 host species ranging from mammals to insects 267:310 The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. 36944617 2 16 theme bacteria 562:569 arg1 strains 551:557 different strains 541:557 different strains of bacteria 541:569 To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. 36944617 5 17 theme mechanistic 1060:1070 arg1 framework 1072:1080 a mechanistic framework 1058:1080 a mechanistic framework for understanding the establishment and stability of a multi-species intestinal microbiome 1058:1171 Our results provide a mechanistic framework for understanding the establishment and stability of a multi-species intestinal microbiome. 36944617 0 18 theme physical 12:19 arg1 niche 21:25 A symbiotic physical niche 0:25 A symbiotic physical niche in Drosophila melanogaster 0:52 A symbiotic physical niche in Drosophila melanogaster regulates stable association of a multi-species gut microbiota. 36944617 2 19 theme strains 551:557 arg1 stability 528:536 the stability 524:536 the stability of different strains of bacteria in the fly gut 524:584 To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. 36944617 1 20 theme bacteria 386:393 arg1 species 375:381 key species 371:381 key species of bacteria 371:393 The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. 36944617 4 21 theme initial 834:840 arg1 colonization 842:853 initial colonization 834:853 initial colonization by Lactobacillus species 834:878 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 2 22 theme host 411:414 arg1 specificity 416:426 host specificity 411:426 host specificity 411:426 To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. 36944617 2 23 theme pulse-chase 471:481 arg1 protocols 483:491 microbial pulse-chase protocols 461:491 microbial pulse-chase protocols 461:491 To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. 36944617 2 24 theme different 541:549 arg1 strains 551:557 different strains 541:557 different strains of bacteria 541:569 To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. 36944617 5 25 theme multi-species 1137:1149 arg1 microbiome 1162:1171 a multi-species intestinal microbiome 1135:1171 a multi-species intestinal microbiome 1135:1171 Our results provide a mechanistic framework for understanding the establishment and stability of a multi-species intestinal microbiome. 36944617 2 26 theme microbial 461:469 arg1 protocols 483:491 microbial pulse-chase protocols 461:491 microbial pulse-chase protocols 461:491 To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. 36944617 4 27 theme unrelated 991:999 arg1 commensals 1001:1010 unrelated commensals 991:1010 unrelated commensals in the Acetobacter genus 991:1035 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 5 28 theme intestinal 1151:1160 arg1 microbiome 1162:1171 a multi-species intestinal microbiome 1135:1171 a multi-species intestinal microbiome 1135:1171 Our results provide a mechanistic framework for understanding the establishment and stability of a multi-species intestinal microbiome. 36944617 4 29 theme secondary 965:973 arg1 colonization 975:986 secondary colonization 965:986 secondary colonization 965:986 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 2 30 theme fly 578:580 arg1 gut 582:584 the fly gut 574:584 the fly gut 574:584 To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. 36944617 4 31 theme strain 822:827 arg1 colonizers 799:808 secondary colonizers 789:808 secondary colonizers of the same strain 789:827 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 4 32 theme secretion 946:954 arg1 production 918:927 production 918:927 production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus 918:1035 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 3 33 theme strain-level 681:692 arg1 specificity 694:704 strain-level specificity 681:704 strain-level specificity 681:704 We show that a host-constructed physical niche in the foregut selectively binds bacteria with strain-level specificity, stabilizing their colonization. 36944617 3 34 theme physical 619:626 arg1 niche 628:632 a host-constructed physical niche 600:632 a host-constructed physical niche in the foregut 600:647 We show that a host-constructed physical niche in the foregut selectively binds bacteria with strain-level specificity, stabilizing their colonization. 36944617 1 35 theme microbiome 209:218 arg1 composition 220:230 microbiome composition 209:230 microbiome composition 209:230 The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. 36944617 4 36 theme glycan-rich 934:944 arg1 secretion 946:954 a glycan-rich secretion 932:954 a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus 932:1035 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 1 37 from diet 179:182 arg1 environment 192:202 the environment 188:202 the environment 188:202 The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. 36944617 1 37 from diet 179:182 arg1 bacteria 161:168 diverse bacteria 153:168 diverse bacteria from the diet 153:182 The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. 36944617 4 38 theme Primary 739:745 arg1 colonizers 747:756 Primary colonizers 739:756 Primary colonizers 739:756 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 4 39 theme same 817:820 arg1 strain 822:827 the same strain 813:827 the same strain 813:827 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 4 40 theme Acetobacter 1019:1029 arg1 genus 1031:1035 the Acetobacter genus 1015:1035 the Acetobacter genus 1015:1035 Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. 36944617 2 41 from stability 528:536 arg1 gut 582:584 the fly gut 574:584 the fly gut 574:584 To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. 36944617 0 42 theme stable 64:69 arg1 association 71:81 stable association 64:81 stable association of a multi-species gut microbiota 64:115 A symbiotic physical niche in Drosophila melanogaster regulates stable association of a multi-species gut microbiota. 36944617 0 43 from niche 21:25 arg1 melanogaster 41:52 Drosophila melanogaster 30:52 Drosophila melanogaster 30:52 A symbiotic physical niche in Drosophila melanogaster regulates stable association of a multi-species gut microbiota. 36944617 3 44 theme host-constructed 602:617 arg1 niche 628:632 a host-constructed physical niche 600:632 a host-constructed physical niche in the foregut 600:647 We show that a host-constructed physical niche in the foregut selectively binds bacteria with strain-level specificity, stabilizing their colonization. 36527793 3 0 theme ideal 315:319 arg1 system 327:332 an ideal model system 312:332 an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community 312:458 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 3 0 theme ideal 315:319 arg1 fermentation 296:307 Traditional baijiu fermentation 277:307 Traditional baijiu fermentation 277:307 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 0 1 from function 16:23 arg1 sauce-flavor 39:50 sauce-flavor 39:50 sauce-flavor 39:50 Composition and function of viruses in sauce-flavor baijiu fermentation. 36527793 5 2 theme Viral 651:655 arg1 communities 657:667 Viral communities 651:667 Viral communities in the fermented grains and fermentation environment 651:720 Viral communities in the fermented grains and fermentation environment are highly similar. 36527793 9 3 theme growth 1191:1196 arg1 P < 0.05 1205:1212 P < 0.05 1205:1212 P < 0.05 1205:1212 Moreover, we proved that starter phages could significantly inhibit the growth of Bacillus licheniformis in the logarithmic growth stage (P < 0.05) under culture condition. 36527793 9 3 theme growth 1191:1196 arg1 stage 1198:1202 the logarithmic growth stage 1175:1202 the logarithmic growth stage (P < 0.05) 1175:1213 Moreover, we proved that starter phages could significantly inhibit the growth of Bacillus licheniformis in the logarithmic growth stage (P < 0.05) under culture condition. 36527793 3 4 theme model 321:325 arg1 system 327:332 an ideal model system 312:332 an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community 312:458 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 3 4 theme model 321:325 arg1 fermentation 296:307 Traditional baijiu fermentation 277:307 Traditional baijiu fermentation 277:307 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 9 5 theme culture 1221:1227 arg1 condition 1229:1237 culture condition 1221:1237 culture condition 1221:1237 Moreover, we proved that starter phages could significantly inhibit the growth of Bacillus licheniformis in the logarithmic growth stage (P < 0.05) under culture condition. 36527793 1 6 dep abundant 92:99 arg1 associated 112:121 associated 112:121 associated with quality and safety of traditional fermented foods 112:176 Viruses are highly abundant in nature, associated with quality and safety of traditional fermented foods. 36527793 10 7 theme functional 1253:1262 arg1 annotations 1264:1274 the functional annotations 1249:1274 the functional annotations 1249:1274 Based on the functional annotations, viruses and bacteria both showed high distribution of genes related to amino acid and carbohydrate metabolism. 36527793 4 8 theme fermentation 571:582 arg1 environment 584:594 fermentation environment 571:594 fermentation environment 571:594 Equipped with cutting-edge viral metagenomics, we investigated the viral community in the fermented grain and fermentation environment, as well as their contribution to baijiu fermentation. 36527793 0 9 from Composition 0:10 arg1 sauce-flavor 39:50 sauce-flavor 39:50 sauce-flavor 39:50 Composition and function of viruses in sauce-flavor baijiu fermentation. 36527793 6 10 theme family 832:837 arg1 Inoviridae 839:848 the family Inoviridae 828:848 the family Inoviridae 828:848 The dominant viruses were bacteriophages, mainly including the order Caudovirales and the family Inoviridae. 36527793 11 11 theme polysaccharides 1565:1579 arg1 decomposition 1540:1552 the decomposition 1536:1552 the decomposition of complex polysaccharides during fermentation 1536:1599 In addition, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes were also identified in viruses, indicating that viruses were involved in the decomposition of complex polysaccharides during fermentation. 36527793 9 12 theme logarithmic 1179:1189 arg1 P < 0.05 1205:1212 P < 0.05 1205:1212 P < 0.05 1205:1212 Moreover, we proved that starter phages could significantly inhibit the growth of Bacillus licheniformis in the logarithmic growth stage (P < 0.05) under culture condition. 36527793 9 12 theme logarithmic 1179:1189 arg1 stage 1198:1202 the logarithmic growth stage 1175:1202 the logarithmic growth stage (P < 0.05) 1175:1213 Moreover, we proved that starter phages could significantly inhibit the growth of Bacillus licheniformis in the logarithmic growth stage (P < 0.05) under culture condition. 36527793 7 13 dep correlated 954:963 arg1 P < 0.01 966:973 P < 0.01 966:973 P < 0.01 966:973 Furtherly, association network analysis showed that viruses and bacteria were significantly negatively correlated (P < 0.01). 36527793 8 14 theme fungal 1037:1042 arg1 P < 0.05 1056:1063 P < 0.05 1056:1063 P < 0.05 1056:1063 Viral diversity could significantly influence bacterial and fungal succession (P < 0.05). 36527793 8 14 theme fungal 1037:1042 arg1 succession 1044:1053 bacterial and fungal succession 1023:1053 bacterial and fungal succession (P < 0.05) 1023:1064 Viral diversity could significantly influence bacterial and fungal succession (P < 0.05). 36527793 10 15 theme related 1337:1343 arg1 genes 1331:1335 genes 1331:1335 genes related to amino acid and carbohydrate metabolism 1331:1385 Based on the functional annotations, viruses and bacteria both showed high distribution of genes related to amino acid and carbohydrate metabolism. 36527793 1 16 theme fermented 162:170 arg1 foods 172:176 traditional fermented foods 150:176 traditional fermented foods 150:176 Viruses are highly abundant in nature, associated with quality and safety of traditional fermented foods. 36527793 11 17 theme abundant 1401:1408 arg1 CAZyme 1448:1453 CAZyme 1448:1453 CAZyme 1448:1453 In addition, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes were also identified in viruses, indicating that viruses were involved in the decomposition of complex polysaccharides during fermentation. 36527793 11 17 theme abundant 1401:1408 arg1 enzyme 1440:1445 abundant auxiliary carbohydrate-active enzyme 1401:1445 abundant auxiliary carbohydrate-active enzyme (CAZyme) genes 1401:1460 In addition, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes were also identified in viruses, indicating that viruses were involved in the decomposition of complex polysaccharides during fermentation. 36527793 4 18 theme viral 488:492 arg1 metagenomics 494:505 cutting-edge viral metagenomics 475:505 cutting-edge viral metagenomics 475:505 Equipped with cutting-edge viral metagenomics, we investigated the viral community in the fermented grain and fermentation environment, as well as their contribution to baijiu fermentation. 36527793 10 19 dep viruses 1277:1283 arg1 both 1298:1301 both 1298:1301 both 1298:1301 Based on the functional annotations, viruses and bacteria both showed high distribution of genes related to amino acid and carbohydrate metabolism. 36527793 2 20 theme food 260:263 arg1 microbiome 265:274 food microbiome 260:274 food microbiome 260:274 However, the overall viral diversity and function are still poorly understood in food microbiome. 36527793 6 21 dep Caudovirales 811:822 arg1 including 791:799 including 791:799 including 791:799 The dominant viruses were bacteriophages, mainly including the order Caudovirales and the family Inoviridae. 36527793 1 22 theme foods 172:176 arg1 safety 140:145 safety 140:145 safety 140:145 Viruses are highly abundant in nature, associated with quality and safety of traditional fermented foods. 36527793 1 22 theme foods 172:176 arg1 quality 128:134 quality 128:134 quality 128:134 Viruses are highly abundant in nature, associated with quality and safety of traditional fermented foods. 36527793 3 23 theme viruses 375:381 arg1 function 363:370 function 363:370 function 363:370 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 3 23 theme viruses 375:381 arg1 diversity 349:357 diversity 349:357 diversity 349:357 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 4 24 theme cutting-edge 475:486 arg1 metagenomics 494:505 cutting-edge viral metagenomics 475:505 cutting-edge viral metagenomics 475:505 Equipped with cutting-edge viral metagenomics, we investigated the viral community in the fermented grain and fermentation environment, as well as their contribution to baijiu fermentation. 36527793 6 25 theme order 805:809 arg1 Caudovirales 811:822 the order Caudovirales 801:822 the order Caudovirales 801:822 The dominant viruses were bacteriophages, mainly including the order Caudovirales and the family Inoviridae. 36527793 3 26 theme stable 405:410 arg1 operation 412:420 stable operation 405:420 stable operation 405:420 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 4 27 theme fermented 551:559 arg1 grain 561:565 the fermented grain 547:565 the fermented grain 547:565 Equipped with cutting-edge viral metagenomics, we investigated the viral community in the fermented grain and fermentation environment, as well as their contribution to baijiu fermentation. 36527793 10 28 theme carbohydrate 1363:1374 arg1 metabolism 1376:1385 carbohydrate metabolism 1363:1385 carbohydrate metabolism 1363:1385 Based on the functional annotations, viruses and bacteria both showed high distribution of genes related to amino acid and carbohydrate metabolism. 36527793 11 29 theme enzyme 1440:1445 arg1 genes 1456:1460 abundant auxiliary carbohydrate-active enzyme (CAZyme) genes 1401:1460 abundant auxiliary carbohydrate-active enzyme (CAZyme) genes 1401:1460 In addition, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes were also identified in viruses, indicating that viruses were involved in the decomposition of complex polysaccharides during fermentation. 36527793 7 30 theme association 862:872 arg1 analysis 882:889 association network analysis 862:889 association network analysis 862:889 Furtherly, association network analysis showed that viruses and bacteria were significantly negatively correlated (P < 0.01). 36527793 4 31 theme baijiu 630:635 arg1 fermentation 637:648 baijiu fermentation 630:648 baijiu fermentation 630:648 Equipped with cutting-edge viral metagenomics, we investigated the viral community in the fermented grain and fermentation environment, as well as their contribution to baijiu fermentation. 36527793 3 32 theme Traditional 277:287 arg1 system 327:332 an ideal model system 312:332 an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community 312:458 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 3 32 theme Traditional 277:287 arg1 fermentation 296:307 Traditional baijiu fermentation 277:307 Traditional baijiu fermentation 277:307 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 1 33 theme traditional 150:160 arg1 foods 172:176 traditional fermented foods 150:176 traditional fermented foods 150:176 Viruses are highly abundant in nature, associated with quality and safety of traditional fermented foods. 36527793 9 34 theme licheniformis 1158:1170 arg1 growth 1139:1144 the growth 1135:1144 the growth of Bacillus licheniformis 1135:1170 Moreover, we proved that starter phages could significantly inhibit the growth of Bacillus licheniformis in the logarithmic growth stage (P < 0.05) under culture condition. 36527793 11 35 theme auxiliary 1410:1418 arg1 CAZyme 1448:1453 CAZyme 1448:1453 CAZyme 1448:1453 In addition, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes were also identified in viruses, indicating that viruses were involved in the decomposition of complex polysaccharides during fermentation. 36527793 11 35 theme auxiliary 1410:1418 arg1 enzyme 1440:1445 abundant auxiliary carbohydrate-active enzyme 1401:1445 abundant auxiliary carbohydrate-active enzyme (CAZyme) genes 1401:1460 In addition, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes were also identified in viruses, indicating that viruses were involved in the decomposition of complex polysaccharides during fermentation. 36527793 12 36 theme traditional 1701:1711 arg1 fermentation 1713:1724 traditional fermentation 1701:1724 traditional fermentation 1701:1724 Our results revealed that viruses could crucially affect microbial community and metabolism during traditional fermentation. 36527793 11 37 theme complex 1557:1563 arg1 polysaccharides 1565:1579 complex polysaccharides 1557:1579 complex polysaccharides 1557:1579 In addition, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes were also identified in viruses, indicating that viruses were involved in the decomposition of complex polysaccharides during fermentation. 36527793 10 38 theme amino 1348:1352 arg1 acid 1354:1357 amino acid 1348:1357 amino acid 1348:1357 Based on the functional annotations, viruses and bacteria both showed high distribution of genes related to amino acid and carbohydrate metabolism. 36527793 3 39 theme domesticated 427:438 arg1 community 450:458 domesticated microbial community 427:458 domesticated microbial community 427:458 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 0 40 theme viruses 28:34 arg1 function 16:23 function 16:23 function 16:23 Composition and function of viruses in sauce-flavor baijiu fermentation. 36527793 0 40 theme viruses 28:34 arg1 Composition 0:10 Composition 0:10 Composition 0:10 Composition and function of viruses in sauce-flavor baijiu fermentation. 36527793 4 41 theme viral 528:532 arg1 community 534:542 the viral community 524:542 the viral community in the fermented grain and fermentation environment 524:594 Equipped with cutting-edge viral metagenomics, we investigated the viral community in the fermented grain and fermentation environment, as well as their contribution to baijiu fermentation. 36527793 4 42 from community 534:542 arg1 grain 561:565 the fermented grain 547:565 the fermented grain 547:565 Equipped with cutting-edge viral metagenomics, we investigated the viral community in the fermented grain and fermentation environment, as well as their contribution to baijiu fermentation. 36527793 4 42 from community 534:542 arg1 environment 584:594 fermentation environment 571:594 fermentation environment 571:594 Equipped with cutting-edge viral metagenomics, we investigated the viral community in the fermented grain and fermentation environment, as well as their contribution to baijiu fermentation. 36527793 10 43 theme high 1310:1313 arg1 distribution 1315:1326 high distribution 1310:1326 high distribution of genes related to amino acid and carbohydrate metabolism 1310:1385 Based on the functional annotations, viruses and bacteria both showed high distribution of genes related to amino acid and carbohydrate metabolism. 36527793 3 44 theme microbial 440:448 arg1 community 450:458 domesticated microbial community 427:458 domesticated microbial community 427:458 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 10 45 theme genes 1331:1335 arg1 distribution 1315:1326 high distribution 1310:1326 high distribution of genes related to amino acid and carbohydrate metabolism 1310:1385 Based on the functional annotations, viruses and bacteria both showed high distribution of genes related to amino acid and carbohydrate metabolism. 36527793 12 46 theme microbial 1659:1667 arg1 community 1669:1677 microbial community 1659:1677 microbial community 1659:1677 Our results revealed that viruses could crucially affect microbial community and metabolism during traditional fermentation. 36527793 5 47 theme fermented 676:684 arg1 grains 686:691 the fermented grains 672:691 the fermented grains 672:691 Viral communities in the fermented grains and fermentation environment are highly similar. 36527793 3 48 dep diversity 349:357 arg1 the 345:347 the 345:347 the 345:347 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 3 49 theme easy 392:395 arg1 access 397:402 easy access 392:402 easy access 392:402 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 2 50 theme viral 200:204 arg1 diversity 206:214 the overall viral diversity 188:214 the overall viral diversity 188:214 However, the overall viral diversity and function are still poorly understood in food microbiome. 36527793 8 51 theme Viral 977:981 arg1 diversity 983:991 Viral diversity 977:991 Viral diversity 977:991 Viral diversity could significantly influence bacterial and fungal succession (P < 0.05). 36527793 5 52 from communities 657:667 arg1 grains 686:691 the fermented grains 672:691 the fermented grains 672:691 Viral communities in the fermented grains and fermentation environment are highly similar. 36527793 5 52 from communities 657:667 arg1 environment 710:720 fermentation environment 697:720 fermentation environment 697:720 Viral communities in the fermented grains and fermentation environment are highly similar. 36527793 3 53 theme baijiu 289:294 arg1 system 327:332 an ideal model system 312:332 an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community 312:458 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 3 53 theme baijiu 289:294 arg1 fermentation 296:307 Traditional baijiu fermentation 277:307 Traditional baijiu fermentation 277:307 Traditional baijiu fermentation is an ideal model system to examine the diversity and function of viruses owing to easy access, stable operation, and domesticated microbial community. 36527793 2 54 theme overall 192:198 arg1 diversity 206:214 the overall viral diversity 188:214 the overall viral diversity 188:214 However, the overall viral diversity and function are still poorly understood in food microbiome. 36527793 8 55 theme bacterial 1023:1031 arg1 P < 0.05 1056:1063 P < 0.05 1056:1063 P < 0.05 1056:1063 Viral diversity could significantly influence bacterial and fungal succession (P < 0.05). 36527793 8 55 theme bacterial 1023:1031 arg1 succession 1044:1053 bacterial and fungal succession 1023:1053 bacterial and fungal succession (P < 0.05) 1023:1064 Viral diversity could significantly influence bacterial and fungal succession (P < 0.05). 36527793 1 56 from nature 104:109 arg1 abundant 92:99 abundant 92:99 abundant 92:99 Viruses are highly abundant in nature, associated with quality and safety of traditional fermented foods. 36527793 5 57 theme fermentation 697:708 arg1 environment 710:720 fermentation environment 697:720 fermentation environment 697:720 Viral communities in the fermented grains and fermentation environment are highly similar. 36527793 11 58 theme carbohydrate-active 1420:1438 arg1 CAZyme 1448:1453 CAZyme 1448:1453 CAZyme 1448:1453 In addition, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes were also identified in viruses, indicating that viruses were involved in the decomposition of complex polysaccharides during fermentation. 36527793 11 58 theme carbohydrate-active 1420:1438 arg1 enzyme 1440:1445 abundant auxiliary carbohydrate-active enzyme 1401:1445 abundant auxiliary carbohydrate-active enzyme (CAZyme) genes 1401:1460 In addition, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes were also identified in viruses, indicating that viruses were involved in the decomposition of complex polysaccharides during fermentation. 36527793 7 59 theme network 874:880 arg1 analysis 882:889 association network analysis 862:889 association network analysis 862:889 Furtherly, association network analysis showed that viruses and bacteria were significantly negatively correlated (P < 0.01). 36527793 4 60 from contribution 614:625 arg1 grain 561:565 the fermented grain 547:565 the fermented grain 547:565 Equipped with cutting-edge viral metagenomics, we investigated the viral community in the fermented grain and fermentation environment, as well as their contribution to baijiu fermentation. 36527793 4 60 from contribution 614:625 arg1 environment 584:594 fermentation environment 571:594 fermentation environment 571:594 Equipped with cutting-edge viral metagenomics, we investigated the viral community in the fermented grain and fermentation environment, as well as their contribution to baijiu fermentation. 36527793 6 61 theme dominant 746:753 arg1 bacteriophages 768:781 bacteriophages 768:781 bacteriophages 768:781 The dominant viruses were bacteriophages, mainly including the order Caudovirales and the family Inoviridae. 36527793 6 61 theme dominant 746:753 arg1 viruses 755:761 The dominant viruses 742:761 The dominant viruses 742:761 The dominant viruses were bacteriophages, mainly including the order Caudovirales and the family Inoviridae. 36527793 1 62 from abundant 92:99 arg1 nature 104:109 nature 104:109 nature 104:109 Viruses are highly abundant in nature, associated with quality and safety of traditional fermented foods. 36527793 9 63 theme starter 1092:1098 arg1 phages 1100:1105 starter phages 1092:1105 starter phages 1092:1105 Moreover, we proved that starter phages could significantly inhibit the growth of Bacillus licheniformis in the logarithmic growth stage (P < 0.05) under culture condition. 36409410 0 0 theme anaerobic 89:97 arg1 effluents 99:107 anaerobic effluents 89:107 anaerobic effluents 89:107 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 2 1 from flux 460:463 arg1 > 800 h 528:534 > 800 h 528:534 > 800 h 528:534 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 2 1 from flux 460:463 arg1 tests 521:525 long-term operation tests 501:525 long-term operation tests (> 800 h) 501:535 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 9 2 theme lower 1594:1598 arg1 stability 1600:1608 a lower stability 1592:1608 a lower stability 1592:1608 Regarding the operation performance, PVDF showed a lower stability and suffered a severe degradation, resulting in a lower thickness and perforations. 36409410 1 3 theme fouling 178:184 arg1 Characterisation 154:169 Characterisation 154:169 Characterisation of the fouling attached to PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery 154:269 Characterisation of the fouling attached to PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery was carried out. 36409410 2 4 theme operation 511:519 arg1 > 800 h 528:534 > 800 h 528:534 > 800 h 528:534 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 2 4 theme operation 511:519 arg1 tests 521:525 long-term operation tests 501:525 long-term operation tests (> 800 h) 501:535 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 0 5 from characterisation 8:23 arg1 contactors 42:51 PVDF membrane contactors 28:51 PVDF membrane contactors 28:51 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 4 6 theme phosphate 853:861 arg1 salts 863:867 different calcium and phosphate salts 831:867 different calcium and phosphate salts 831:867 Both organic and inorganic fouling were observed, and the main foulants were proteins, polysaccharides, and different calcium and phosphate salts. 36409410 5 7 theme significant 878:888 arg1 amount 890:895 a significant amount 876:895 a significant amount of live cells 876:909 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 5 7 theme significant 878:888 arg1 cells 905:909 live cells 900:909 live cells 900:909 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 10 8 theme fouling 1794:1800 arg1 depositions 1802:1812 the fouling depositions 1790:1812 the fouling depositions 1790:1812 Finally, the decrease in the methane recovery performance of both membranes was associated with the fouling depositions. 36409410 8 9 dep detected 1463:1470 arg1 observed 1533:1540 observed 1533:1540 was observed 1529:1540 Irreversible fouling remained on both membranes after the extraction, although a higher irreversible fouling was detected in the mPVDF; however, a complete polysaccharide removal was observed. 36409410 6 10 theme fouling 996:1002 arg1 composition 1009:1019 the fouling cake composition 992:1019 the fouling cake composition 992:1019 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 6 10 theme fouling 996:1002 arg1 heterogeneous 1031:1043 heterogeneous 1031:1043 heterogeneous 1031:1043 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 7 11 theme stronger 1286:1293 arg1 interaction 1319:1329 a stronger hydrophobic-hydrophobic interaction 1284:1329 a stronger hydrophobic-hydrophobic interaction with the foulants 1284:1347 The mPVDF suffered a more severe fouling, likely owing to a stronger hydrophobic-hydrophobic interaction with the foulants. 36409410 6 12 theme cake 1220:1223 arg1 surfaces 1204:1211 the lower and upper surfaces 1184:1211 the lower and upper surfaces of the cake 1184:1223 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 9 13 theme operation 1557:1565 arg1 performance 1567:1577 the operation performance 1553:1577 the operation performance 1553:1577 Regarding the operation performance, PVDF showed a lower stability and suffered a severe degradation, resulting in a lower thickness and perforations. 36409410 4 14 theme inorganic 740:748 arg1 fouling 750:756 Both organic and inorganic fouling 723:756 Both organic and inorganic fouling 723:756 Both organic and inorganic fouling were observed, and the main foulants were proteins, polysaccharides, and different calcium and phosphate salts. 36409410 7 15 with interaction 1319:1329 arg1 foulants 1340:1347 the foulants 1336:1347 the foulants 1336:1347 The mPVDF suffered a more severe fouling, likely owing to a stronger hydrophobic-hydrophobic interaction with the foulants. 36409410 2 16 from effluent 489:496 arg1 > 800 h 528:534 > 800 h 528:534 > 800 h 528:534 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 2 16 from effluent 489:496 arg1 tests 521:525 long-term operation tests 501:525 long-term operation tests (> 800 h) 501:535 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 6 17 theme cake 1137:1140 arg1 centre 1123:1128 the bulk centre 1114:1128 the bulk centre of the cake 1114:1140 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 2 18 theme PVDF 312:315 arg1 membrane 317:324 A commercial flat-sheet PVDF membrane 288:324 A commercial flat-sheet PVDF membrane 288:324 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 6 19 from surfaces 1204:1211 arg1 located 1173:1179 located 1173:1179 located 1173:1179 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 4 20 theme different 831:839 arg1 salts 863:867 different calcium and phosphate salts 831:867 different calcium and phosphate salts 831:867 Both organic and inorganic fouling were observed, and the main foulants were proteins, polysaccharides, and different calcium and phosphate salts. 36409410 2 21 theme flat-sheet 301:310 arg1 membrane 317:324 A commercial flat-sheet PVDF membrane 288:324 A commercial flat-sheet PVDF membrane 288:324 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 5 22 dep detected 915:922 arg1 PVDF 976:979 the non-modified PVDF 959:979 the non-modified PVDF 959:979 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 8 23 theme higher 1431:1436 arg1 fouling 1451:1457 a higher irreversible fouling 1429:1457 a higher irreversible fouling 1429:1457 Irreversible fouling remained on both membranes after the extraction, although a higher irreversible fouling was detected in the mPVDF; however, a complete polysaccharide removal was observed. 36409410 1 24 attach attached 186:193 arg1 membranes 203:211 PVDF membranes 198:211 PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery 198:269 Characterisation of the fouling attached to PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery was carried out. 36409410 1 24 attach attached 186:193 arg2 fouling 178:184 the fouling 174:184 the fouling attached to PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery 174:269 Characterisation of the fouling attached to PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery was carried out. 36409410 6 25 theme inorganic 1086:1094 arg1 fouling 1096:1102 the inorganic fouling 1082:1102 the inorganic fouling mainly in the bulk centre of the cake 1082:1140 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 2 26 theme commercial 290:299 arg1 membrane 317:324 A commercial flat-sheet PVDF membrane 288:324 A commercial flat-sheet PVDF membrane 288:324 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 8 27 located detected 1463:1470 arg1 mPVDF 1479:1483 the mPVDF 1475:1483 the mPVDF 1475:1483 Irreversible fouling remained on both membranes after the extraction, although a higher irreversible fouling was detected in the mPVDF; however, a complete polysaccharide removal was observed. 36409410 8 27 located detected 1463:1470 arg2 fouling 1451:1457 a higher irreversible fouling 1429:1457 a higher irreversible fouling 1429:1457 Irreversible fouling remained on both membranes after the extraction, although a higher irreversible fouling was detected in the mPVDF; however, a complete polysaccharide removal was observed. 36409410 1 28 theme PVDF 198:201 arg1 membranes 203:211 PVDF membranes 198:211 PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery 198:269 Characterisation of the fouling attached to PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery was carried out. 36409410 2 29 theme anaerobic 471:479 arg1 effluent 489:496 an anaerobic reactor effluent 468:496 an anaerobic reactor effluent in long-term operation tests (> 800 h) 468:535 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 6 30 theme upper 1198:1202 arg1 surfaces 1204:1211 the lower and upper surfaces 1184:1211 the lower and upper surfaces of the cake 1184:1223 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 10 31 theme methane 1723:1729 arg1 performance 1740:1750 the methane recovery performance 1719:1750 the methane recovery performance of both membranes 1719:1768 Finally, the decrease in the methane recovery performance of both membranes was associated with the fouling depositions. 36409410 10 32 theme recovery 1731:1738 arg1 performance 1740:1750 the methane recovery performance 1719:1750 the methane recovery performance of both membranes 1719:1768 Finally, the decrease in the methane recovery performance of both membranes was associated with the fouling depositions. 36409410 7 33 theme severe 1252:1257 arg1 fouling 1259:1265 a more severe fouling 1245:1265 a more severe fouling 1245:1265 The mPVDF suffered a more severe fouling, likely owing to a stronger hydrophobic-hydrophobic interaction with the foulants. 36409410 0 34 theme Fouling 0:6 arg1 characterisation 8:23 Fouling characterisation 0:23 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 0:152 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 4 35 theme calcium 841:847 arg1 salts 863:867 different calcium and phosphate salts 831:867 different calcium and phosphate salts 831:867 Both organic and inorganic fouling were observed, and the main foulants were proteins, polysaccharides, and different calcium and phosphate salts. 36409410 4 36 theme organic 728:734 arg1 fouling 750:756 Both organic and inorganic fouling 723:756 Both organic and inorganic fouling 723:756 Both organic and inorganic fouling were observed, and the main foulants were proteins, polysaccharides, and different calcium and phosphate salts. 36409410 0 37 theme PVDF 28:31 arg1 contactors 42:51 PVDF membrane contactors 28:51 PVDF membrane contactors 28:51 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 6 38 theme organic 1150:1156 arg1 fouling 1158:1164 the organic fouling 1146:1164 the organic fouling mainly located in the lower and upper surfaces of the cake 1146:1223 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 0 39 theme organofluorosilanisation 128:151 arg1 effect 110:115 effect 110:115 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 0:152 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 8 40 theme Irreversible 1350:1361 arg1 fouling 1363:1369 Irreversible fouling 1350:1369 Irreversible fouling 1350:1369 Irreversible fouling remained on both membranes after the extraction, although a higher irreversible fouling was detected in the mPVDF; however, a complete polysaccharide removal was observed. 36409410 10 41 theme membranes 1760:1768 arg1 performance 1740:1750 the methane recovery performance 1719:1750 the methane recovery performance of both membranes 1719:1768 Finally, the decrease in the methane recovery performance of both membranes was associated with the fouling depositions. 36409410 2 42 theme continuous 449:458 arg1 flux 460:463 a continuous flux 447:463 a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h) 447:535 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 6 43 theme bulk 1118:1121 arg1 centre 1123:1128 the bulk centre 1114:1128 the bulk centre of the cake 1114:1140 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 3 44 dep water 697:701 arg1 solutions 712:720 solutions 712:720 solutions 712:720 The fouling cakes were studied by the membrane autopsy after these tests, combining a staining technique, FTIR, and FESEM-EDX, and the fouling extraction with water and NaOH solutions. 36409410 0 45 theme surface 120:126 arg1 organofluorosilanisation 128:151 surface organofluorosilanisation 120:151 surface organofluorosilanisation 120:151 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 2 46 from tests 521:525 arg1 flux 460:463 a continuous flux 447:463 a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h) 447:535 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 3 47 theme membrane 576:583 arg1 autopsy 585:591 the membrane autopsy 572:591 the membrane autopsy 572:591 The fouling cakes were studied by the membrane autopsy after these tests, combining a staining technique, FTIR, and FESEM-EDX, and the fouling extraction with water and NaOH solutions. 36409410 8 48 theme polysaccharide 1506:1519 arg1 removal 1521:1527 a complete polysaccharide removal 1495:1527 a complete polysaccharide removal 1495:1527 Irreversible fouling remained on both membranes after the extraction, although a higher irreversible fouling was detected in the mPVDF; however, a complete polysaccharide removal was observed. 36409410 1 49 theme anaerobic 225:233 arg1 effluent 235:242 an anaerobic effluent 222:242 an anaerobic effluent for dissolved CH4 recovery 222:269 Characterisation of the fouling attached to PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery was carried out. 36409410 2 50 theme long-term 501:509 arg1 > 800 h 528:534 > 800 h 528:534 > 800 h 528:534 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 2 50 theme long-term 501:509 arg1 tests 521:525 long-term operation tests 501:525 long-term operation tests (> 800 h) 501:535 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 8 51 theme complete 1497:1504 arg1 removal 1521:1527 a complete polysaccharide removal 1495:1527 a complete polysaccharide removal 1495:1527 Irreversible fouling remained on both membranes after the extraction, although a higher irreversible fouling was detected in the mPVDF; however, a complete polysaccharide removal was observed. 36409410 6 52 theme lower 1188:1192 arg1 surfaces 1204:1211 the lower and upper surfaces 1184:1211 the lower and upper surfaces of the cake 1184:1223 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 0 53 theme membrane 33:40 arg1 contactors 42:51 PVDF membrane contactors 28:51 PVDF membrane contactors 28:51 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 9 54 theme lower 1660:1664 arg1 thickness 1666:1674 a lower thickness 1658:1674 a lower thickness 1658:1674 Regarding the operation performance, PVDF showed a lower stability and suffered a severe degradation, resulting in a lower thickness and perforations. 36409410 6 55 theme cake 1004:1007 arg1 composition 1009:1019 the fouling cake composition 992:1019 the fouling cake composition 992:1019 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 6 55 theme cake 1004:1007 arg1 heterogeneous 1031:1043 heterogeneous 1031:1043 heterogeneous 1031:1043 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 0 56 theme dissolved 57:65 arg1 recovery 75:82 dissolved methane recovery 57:82 dissolved methane recovery from anaerobic effluents 57:107 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 5 57 located detected 915:922 arg2 cells 905:909 live cells 900:909 live cells 900:909 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 5 57 located detected 915:922 arg2 amount 890:895 a significant amount 876:895 a significant amount of live cells 876:909 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 5 57 located detected 915:922 arg1 cake 939:942 the fouling cake 927:942 the fouling cake 927:942 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 0 58 theme methane 67:73 arg1 recovery 75:82 dissolved methane recovery 57:82 dissolved methane recovery from anaerobic effluents 57:107 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 7 59 theme hydrophobic-hydrophobic 1295:1317 arg1 interaction 1319:1329 a stronger hydrophobic-hydrophobic interaction 1284:1329 a stronger hydrophobic-hydrophobic interaction with the foulants 1284:1347 The mPVDF suffered a more severe fouling, likely owing to a stronger hydrophobic-hydrophobic interaction with the foulants. 36409410 2 60 theme organofluorosilanes 367:385 arg1 grafting 355:362 grafting 355:362 grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity 355:427 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 2 61 theme reactor 481:487 arg1 effluent 489:496 an anaerobic reactor effluent 468:496 an anaerobic reactor effluent in long-term operation tests (> 800 h) 468:535 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 9 62 theme severe 1625:1630 arg1 degradation 1632:1642 a severe degradation 1623:1642 a severe degradation 1623:1642 Regarding the operation performance, PVDF showed a lower stability and suffered a severe degradation, resulting in a lower thickness and perforations. 36409410 6 63 theme located 1173:1179 arg1 fouling 1158:1164 the organic fouling 1146:1164 the organic fouling mainly located in the lower and upper surfaces of the cake 1146:1223 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 5 64 theme live 900:903 arg1 cells 905:909 live cells 900:909 live cells 900:909 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 3 65 theme fouling 673:679 arg1 extraction 681:690 the fouling extraction 669:690 the fouling extraction 669:690 The fouling cakes were studied by the membrane autopsy after these tests, combining a staining technique, FTIR, and FESEM-EDX, and the fouling extraction with water and NaOH solutions. 36409410 4 66 theme main 781:784 arg1 foulants 786:793 the main foulants 777:793 the main foulants 777:793 Both organic and inorganic fouling were observed, and the main foulants were proteins, polysaccharides, and different calcium and phosphate salts. 36409410 4 66 theme main 781:784 arg1 proteins 800:807 proteins 800:807 proteins 800:807 Both organic and inorganic fouling were observed, and the main foulants were proteins, polysaccharides, and different calcium and phosphate salts. 36409410 6 67 from fouling 1096:1102 arg1 centre 1123:1128 the bulk centre 1114:1128 the bulk centre of the cake 1114:1140 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 5 68 theme cells 905:909 arg1 amount 890:895 a significant amount 876:895 a significant amount of live cells 876:909 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 5 68 theme cells 905:909 arg1 cells 905:909 live cells 900:909 live cells 900:909 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 6 69 from located 1173:1179 arg1 surfaces 1204:1211 the lower and upper surfaces 1184:1211 the lower and upper surfaces of the cake 1184:1223 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 1 70 theme dissolved 248:256 arg1 recovery 262:269 dissolved CH4 recovery 248:269 dissolved CH4 recovery 248:269 Characterisation of the fouling attached to PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery was carried out. 36409410 8 71 theme irreversible 1438:1449 arg1 fouling 1451:1457 a higher irreversible fouling 1429:1457 a higher irreversible fouling 1429:1457 Irreversible fouling remained on both membranes after the extraction, although a higher irreversible fouling was detected in the mPVDF; however, a complete polysaccharide removal was observed. 36409410 5 72 theme non-modified 963:974 arg1 PVDF 976:979 the non-modified PVDF 959:979 the non-modified PVDF 959:979 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 10 73 from decrease 1707:1714 arg1 performance 1740:1750 the methane recovery performance 1719:1750 the methane recovery performance of both membranes 1719:1768 Finally, the decrease in the methane recovery performance of both membranes was associated with the fouling depositions. 36409410 1 74 theme CH4 258:260 arg1 recovery 262:269 dissolved CH4 recovery 248:269 dissolved CH4 recovery 248:269 Characterisation of the fouling attached to PVDF membranes treating an anaerobic effluent for dissolved CH4 recovery was carried out. 36409410 0 75 from effluents 99:107 arg1 recovery 75:82 dissolved methane recovery 57:82 dissolved methane recovery from anaerobic effluents 57:107 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 0 76 dep characterisation 8:23 arg1 effect 110:115 effect 110:115 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 0:152 Fouling characterisation in PVDF membrane contactors for dissolved methane recovery from anaerobic effluents: effect of surface organofluorosilanisation. 36409410 5 77 dep PVDF 976:979 arg1 especially 945:954 especially 945:954 especially 945:954 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 5 78 theme fouling 931:937 arg1 cake 939:942 the fouling cake 927:942 the fouling cake 927:942 Also, a significant amount of live cells was detected on the fouling cake (especially on the non-modified PVDF). 36409410 6 79 from fouling 1158:1164 arg1 centre 1123:1128 the bulk centre 1114:1128 the bulk centre of the cake 1114:1140 Although the fouling cake composition was quite heterogeneous, a stratification was observed, with the inorganic fouling mainly in the bulk centre of the cake and the organic fouling mainly located in the lower and upper surfaces of the cake. 36409410 2 80 theme effluent 489:496 arg1 flux 460:463 a continuous flux 447:463 a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h) 447:535 A commercial flat-sheet PVDF membrane and a PVDF functionalised by grafting of organofluorosilanes (mPVDF) that increased its hydrophobicity were subjected to a continuous flux of an anaerobic reactor effluent in long-term operation tests (> 800 h). 36409410 3 81 theme staining 624:631 arg1 technique 633:641 a staining technique 622:641 a staining technique 622:641 The fouling cakes were studied by the membrane autopsy after these tests, combining a staining technique, FTIR, and FESEM-EDX, and the fouling extraction with water and NaOH solutions. 36409410 3 82 theme fouling 542:548 arg1 cakes 550:554 The fouling cakes 538:554 The fouling cakes 538:554 The fouling cakes were studied by the membrane autopsy after these tests, combining a staining technique, FTIR, and FESEM-EDX, and the fouling extraction with water and NaOH solutions. 35335542 4 0 theme extra 905:909 arg1 step 924:927 an extra crosslinking step 902:927 an extra crosslinking step 902:927 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 5 1 from crosslinking 993:1004 arg1 solutions 950:958 CaCl2 solutions 944:958 CaCl2 solutions 944:958 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 6 2 theme resulting 1253:1261 arg1 scaffolds 1283:1291 the resulting alginate-HA aerogel scaffolds 1249:1291 the resulting alginate-HA aerogel scaffolds 1249:1291 Nitrogen adsorption-desorption (BET) and SEM analyses were performed to assess the textural parameters of the resulting alginate-HA aerogel scaffolds. 35335542 1 3 theme porosity 274:281 arg1 fabrication 92:102 The fabrication 88:102 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity 88:281 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 1 3 theme porosity 274:281 arg1 crucial 286:292 crucial 286:292 crucial 286:292 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 1 4 theme bioactive 107:115 arg1 scaffolds 149:157 bioactive three-dimensional (3D) hydrogel scaffolds 107:157 bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) 107:246 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 4 5 theme gel 886:888 arg1 drying 890:895 extrusion-based 3D-printing and supercritical CO2 gel drying 836:895 extrusion-based 3D-printing and supercritical CO2 gel drying 836:895 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 6 6 theme textural 1226:1233 arg1 parameters 1235:1244 the textural parameters 1222:1244 the textural parameters of the resulting alginate-HA aerogel scaffolds 1222:1291 Nitrogen adsorption-desorption (BET) and SEM analyses were performed to assess the textural parameters of the resulting alginate-HA aerogel scaffolds. 35335542 3 7 theme biodegradation 585:598 arg1 rates 600:604 fast biodegradation rates 580:604 fast biodegradation rates in biological aqueous fluids 580:633 However, these aerogels are usually fragile, with fast biodegradation rates in biological aqueous fluids, and they lack the sterility required for clinical practice. 35335542 1 8 theme inner 203:207 arg1 structure 209:217 a complex inner structure 193:217 a complex inner structure (mesoporous and macroporous) 193:246 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 3 9 theme aqueous 620:626 arg1 fluids 628:633 biological aqueous fluids 609:633 biological aqueous fluids 609:633 However, these aerogels are usually fragile, with fast biodegradation rates in biological aqueous fluids, and they lack the sterility required for clinical practice. 35335542 1 10 theme three-dimensional 117:133 arg1 scaffolds 149:157 bioactive three-dimensional (3D) hydrogel scaffolds 107:157 bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) 107:246 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 5 11 link crosslinked 1112:1122 arg1 scaffolds 1132:1140 highly crosslinked aerogel scaffolds 1105:1140 highly crosslinked aerogel scaffolds 1105:1140 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 4 12 theme aerogel 750:756 arg1 scaffolds 758:766 reinforced alginate-hydroxyapatite (HA) aerogel scaffolds 710:766 reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications 710:787 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 8 13 theme scaffold 1487:1494 arg1 properties 1496:1505 scaffold properties 1487:1505 scaffold properties 1487:1505 The impact of scCO2-based post-sterilization treatment on scaffold properties was also assessed. 35335542 5 14 theme crosslinked 1112:1122 arg1 scaffolds 1132:1140 highly crosslinked aerogel scaffolds 1105:1140 highly crosslinked aerogel scaffolds 1105:1140 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 15 theme glutaraldehyde 964:977 arg1 intermediate 1036:1047 intermediate 1036:1047 intermediate 1036:1047 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 15 theme glutaraldehyde 964:977 arg1 ageing 934:939 Gel ageing 930:939 Gel ageing in CaCl2 solutions 930:958 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 15 theme glutaraldehyde 964:977 arg1 strategies 1083:1092 post-processing reinforcement strategies 1053:1092 post-processing reinforcement strategies 1053:1092 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 15 theme glutaraldehyde 964:977 arg1 GA 980:981 GA 980:981 GA 980:981 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 15 theme glutaraldehyde 964:977 arg1 crosslinking 993:1004 glutaraldehyde (GA) chemical crosslinking 964:1004 glutaraldehyde (GA) chemical crosslinking of aerogels 964:1016 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 6 16 theme aerogel 1275:1281 arg1 scaffolds 1283:1291 the resulting alginate-HA aerogel scaffolds 1249:1291 the resulting alginate-HA aerogel scaffolds 1249:1291 Nitrogen adsorption-desorption (BET) and SEM analyses were performed to assess the textural parameters of the resulting alginate-HA aerogel scaffolds. 35335542 9 17 theme obtained 1530:1537 arg1 porous 1558:1563 porous 1558:1563 porous 1558:1563 The obtained aerogels were dual porous, bio- and hemocompatible, as well as endowed with high bioactivity that is dependent on the HA content. 35335542 9 17 theme obtained 1530:1537 arg1 aerogels 1539:1546 The obtained aerogels 1526:1546 The obtained aerogels 1526:1546 The obtained aerogels were dual porous, bio- and hemocompatible, as well as endowed with high bioactivity that is dependent on the HA content. 35335542 5 18 theme Gel 930:932 arg1 ageing 934:939 Gel ageing 930:939 Gel ageing in CaCl2 solutions 930:958 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 18 theme Gel 930:932 arg1 intermediate 1036:1047 intermediate 1036:1047 intermediate 1036:1047 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 18 theme Gel 930:932 arg1 strategies 1083:1092 post-processing reinforcement strategies 1053:1092 post-processing reinforcement strategies 1053:1092 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 18 theme Gel 930:932 arg1 crosslinking 993:1004 glutaraldehyde (GA) chemical crosslinking 964:1004 glutaraldehyde (GA) chemical crosslinking of aerogels 964:1016 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 2 19 from polysaccharides 452:466 arg1 fabrication 396:406 the fabrication 392:406 the fabrication of functional nanostructured scaffolds from polysaccharides 392:466 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 2 19 from polysaccharides 452:466 arg1 scaffolds 437:445 functional nanostructured scaffolds 411:445 functional nanostructured scaffolds from polysaccharides 411:466 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 4 20 theme alginate-hydroxyapatite 721:743 arg1 scaffolds 758:766 reinforced alginate-hydroxyapatite (HA) aerogel scaffolds 710:766 reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications 710:787 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 0 21 theme Tissue 68:73 arg1 Engineering 75:85 Bone Tissue Engineering 63:85 Bone Tissue Engineering 63:85 3D-Printed, Dual Crosslinked and Sterile Aerogel Scaffolds for Bone Tissue Engineering. 35335542 5 22 from ageing 934:939 arg1 solutions 950:958 CaCl2 solutions 944:958 CaCl2 solutions 944:958 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 2 23 theme scaffolds 437:445 arg1 fabrication 396:406 the fabrication 392:406 the fabrication of functional nanostructured scaffolds from polysaccharides 392:466 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 8 24 theme scCO2-based 1443:1453 arg1 treatment 1474:1482 scCO2-based post-sterilization treatment 1443:1482 scCO2-based post-sterilization treatment 1443:1482 The impact of scCO2-based post-sterilization treatment on scaffold properties was also assessed. 35335542 10 25 theme performance 1745:1755 arg1 optimization 1709:1720 the optimization 1705:1720 the optimization of the physicochemical performance of advanced biomaterials and their sterilization 1705:1804 This work is a step forward towards the optimization of the physicochemical performance of advanced biomaterials and their sterilization. 35335542 6 26 theme Nitrogen 1143:1150 arg1 BET 1175:1177 BET 1175:1177 BET 1175:1177 Nitrogen adsorption-desorption (BET) and SEM analyses were performed to assess the textural parameters of the resulting alginate-HA aerogel scaffolds. 35335542 6 26 theme Nitrogen 1143:1150 arg1 adsorption-desorption 1152:1172 Nitrogen adsorption-desorption 1143:1172 Nitrogen adsorption-desorption (BET) 1143:1178 Nitrogen adsorption-desorption (BET) and SEM analyses were performed to assess the textural parameters of the resulting alginate-HA aerogel scaffolds. 35335542 8 27 theme treatment 1474:1482 arg1 impact 1433:1438 The impact 1429:1438 The impact of scCO2-based post-sterilization treatment on scaffold properties 1429:1505 The impact of scCO2-based post-sterilization treatment on scaffold properties was also assessed. 35335542 0 28 theme 3D-Printed 0:9 arg1 Aerogel 41:47 3D-Printed, Dual Crosslinked and Sterile Aerogel 0:47 3D-Printed, Dual Crosslinked and Sterile Aerogel 0:47 3D-Printed, Dual Crosslinked and Sterile Aerogel Scaffolds for Bone Tissue Engineering. 35335542 6 29 dep adsorption-desorption 1152:1172 arg1 analyses 1188:1195 analyses 1188:1195 analyses 1188:1195 Nitrogen adsorption-desorption (BET) and SEM analyses were performed to assess the textural parameters of the resulting alginate-HA aerogel scaffolds. 35335542 5 30 theme chemical 984:991 arg1 intermediate 1036:1047 intermediate 1036:1047 intermediate 1036:1047 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 30 theme chemical 984:991 arg1 ageing 934:939 Gel ageing 930:939 Gel ageing in CaCl2 solutions 930:958 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 30 theme chemical 984:991 arg1 strategies 1083:1092 post-processing reinforcement strategies 1053:1092 post-processing reinforcement strategies 1053:1092 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 30 theme chemical 984:991 arg1 GA 980:981 GA 980:981 GA 980:981 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 30 theme chemical 984:991 arg1 crosslinking 993:1004 glutaraldehyde (GA) chemical crosslinking 964:1004 glutaraldehyde (GA) chemical crosslinking of aerogels 964:1016 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 3 31 theme clinical 677:684 arg1 practice 686:693 clinical practice 677:693 clinical practice 677:693 However, these aerogels are usually fragile, with fast biodegradation rates in biological aqueous fluids, and they lack the sterility required for clinical practice. 35335542 4 32 theme 3D-printing 852:862 arg1 drying 890:895 extrusion-based 3D-printing and supercritical CO2 gel drying 836:895 extrusion-based 3D-printing and supercritical CO2 gel drying 836:895 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 2 33 theme nanostructured 422:435 arg1 scaffolds 437:445 functional nanostructured scaffolds 411:445 functional nanostructured scaffolds from polysaccharides 411:466 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 3 34 with fragile 566:572 arg1 rates 600:604 fast biodegradation rates 580:604 fast biodegradation rates in biological aqueous fluids 580:633 However, these aerogels are usually fragile, with fast biodegradation rates in biological aqueous fluids, and they lack the sterility required for clinical practice. 35335542 1 35 theme tissue 303:308 arg1 engineering 310:320 bone tissue engineering 298:320 bone tissue engineering (BTE) 298:326 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 1 35 theme tissue 303:308 arg1 BTE 323:325 BTE 323:325 BTE 323:325 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 5 36 theme reinforcement 1069:1081 arg1 ageing 934:939 Gel ageing 930:939 Gel ageing in CaCl2 solutions 930:958 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 36 theme reinforcement 1069:1081 arg1 strategies 1083:1092 post-processing reinforcement strategies 1053:1092 post-processing reinforcement strategies 1053:1092 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 36 theme reinforcement 1069:1081 arg1 crosslinking 993:1004 glutaraldehyde (GA) chemical crosslinking 964:1004 glutaraldehyde (GA) chemical crosslinking of aerogels 964:1016 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 7 37 theme hemolytic 1385:1393 arg1 activity 1395:1402 hemolytic activity 1385:1402 hemolytic activity 1385:1402 The biological evaluation of the aerogel scaffolds was performed regarding cell viability, hemolytic activity and bioactivity for BTE. 35335542 4 38 theme supercritical 868:880 arg1 drying 890:895 extrusion-based 3D-printing and supercritical CO2 gel drying 836:895 extrusion-based 3D-printing and supercritical CO2 gel drying 836:895 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 1 39 dep structure 209:217 arg1 macroporous 235:245 macroporous 235:245 macroporous 235:245 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 1 39 dep structure 209:217 arg1 mesoporous 220:229 mesoporous 220:229 mesoporous 220:229 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 10 40 theme sterilization 1792:1804 arg1 performance 1745:1755 the physicochemical performance 1725:1755 the physicochemical performance of advanced biomaterials and their sterilization 1725:1804 This work is a step forward towards the optimization of the physicochemical performance of advanced biomaterials and their sterilization. 35335542 1 41 with materials 178:186 arg1 structure 209:217 a complex inner structure 193:217 a complex inner structure (mesoporous and macroporous) 193:246 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 9 42 theme high 1615:1618 arg1 bioactivity 1620:1630 high bioactivity 1615:1630 high bioactivity that is dependent on the HA content 1615:1666 The obtained aerogels were dual porous, bio- and hemocompatible, as well as endowed with high bioactivity that is dependent on the HA content. 35335542 0 43 link Crosslinked 17:27 arg1 Aerogel 41:47 3D-Printed, Dual Crosslinked and Sterile Aerogel 0:47 3D-Printed, Dual Crosslinked and Sterile Aerogel 0:47 3D-Printed, Dual Crosslinked and Sterile Aerogel Scaffolds for Bone Tissue Engineering. 35335542 7 44 theme aerogel 1327:1333 arg1 scaffolds 1335:1343 the aerogel scaffolds 1323:1343 the aerogel scaffolds 1323:1343 The biological evaluation of the aerogel scaffolds was performed regarding cell viability, hemolytic activity and bioactivity for BTE. 35335542 1 45 theme interconnected 259:272 arg1 porosity 274:281 highly interconnected porosity 252:281 highly interconnected porosity 252:281 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 4 46 theme crosslinking 911:922 arg1 step 924:927 an extra crosslinking step 902:927 an extra crosslinking step 902:927 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 1 47 theme biocompatible 164:176 arg1 materials 178:186 biocompatible materials 164:186 biocompatible materials with a complex inner structure (mesoporous and macroporous) 164:246 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 10 48 theme advanced 1760:1767 arg1 biomaterials 1769:1780 advanced biomaterials 1760:1780 advanced biomaterials 1760:1780 This work is a step forward towards the optimization of the physicochemical performance of advanced biomaterials and their sterilization. 35335542 4 49 theme CO2 882:884 arg1 drying 890:895 extrusion-based 3D-printing and supercritical CO2 gel drying 836:895 extrusion-based 3D-printing and supercritical CO2 gel drying 836:895 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 7 50 theme biological 1298:1307 arg1 evaluation 1309:1318 The biological evaluation 1294:1318 The biological evaluation of the aerogel scaffolds 1294:1343 The biological evaluation of the aerogel scaffolds was performed regarding cell viability, hemolytic activity and bioactivity for BTE. 35335542 3 51 theme fast 580:583 arg1 rates 600:604 fast biodegradation rates 580:604 fast biodegradation rates in biological aqueous fluids 580:633 However, these aerogels are usually fragile, with fast biodegradation rates in biological aqueous fluids, and they lack the sterility required for clinical practice. 35335542 1 52 theme complex 195:201 arg1 structure 209:217 a complex inner structure 193:217 a complex inner structure (mesoporous and macroporous) 193:246 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 3 53 theme biological 609:618 arg1 fluids 628:633 biological aqueous fluids 609:633 biological aqueous fluids 609:633 However, these aerogels are usually fragile, with fast biodegradation rates in biological aqueous fluids, and they lack the sterility required for clinical practice. 35335542 5 54 theme CaCl2 944:948 arg1 solutions 950:958 CaCl2 solutions 944:958 CaCl2 solutions 944:958 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 2 55 with BTE 472:474 arg1 geometry 494:501 personalized geometry 481:501 personalized geometry 481:501 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 2 55 with BTE 472:474 arg1 composition 517:527 composition 517:527 composition 517:527 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 2 55 with BTE 472:474 arg1 porosity 504:511 porosity 504:511 porosity 504:511 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 6 56 theme scaffolds 1283:1291 arg1 parameters 1235:1244 the textural parameters 1222:1244 the textural parameters of the resulting alginate-HA aerogel scaffolds 1222:1291 Nitrogen adsorption-desorption (BET) and SEM analyses were performed to assess the textural parameters of the resulting alginate-HA aerogel scaffolds. 35335542 3 57 from rates 600:604 arg1 fluids 628:633 biological aqueous fluids 609:633 biological aqueous fluids 609:633 However, these aerogels are usually fragile, with fast biodegradation rates in biological aqueous fluids, and they lack the sterility required for clinical practice. 35335542 0 58 theme Bone 63:66 arg1 Engineering 75:85 Bone Tissue Engineering 63:85 Bone Tissue Engineering 63:85 3D-Printed, Dual Crosslinked and Sterile Aerogel Scaffolds for Bone Tissue Engineering. 35335542 5 59 theme aerogel 1124:1130 arg1 scaffolds 1132:1140 highly crosslinked aerogel scaffolds 1105:1140 highly crosslinked aerogel scaffolds 1105:1140 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 6 60 theme alginate-HA 1263:1273 arg1 scaffolds 1283:1291 the resulting alginate-HA aerogel scaffolds 1249:1291 the resulting alginate-HA aerogel scaffolds 1249:1291 Nitrogen adsorption-desorption (BET) and SEM analyses were performed to assess the textural parameters of the resulting alginate-HA aerogel scaffolds. 35335542 1 61 from materials 178:186 arg1 scaffolds 149:157 bioactive three-dimensional (3D) hydrogel scaffolds 107:157 bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) 107:246 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 1 61 from materials 178:186 arg1 fabrication 92:102 The fabrication 88:102 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity 88:281 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 1 61 from materials 178:186 arg1 crucial 286:292 crucial 286:292 crucial 286:292 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 1 61 from materials 178:186 arg1 porosity 274:281 highly interconnected porosity 252:281 highly interconnected porosity 252:281 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 1 62 theme scaffolds 149:157 arg1 fabrication 92:102 The fabrication 88:102 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity 88:281 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 1 62 theme scaffolds 149:157 arg1 crucial 286:292 crucial 286:292 crucial 286:292 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 4 63 theme reinforced 710:719 arg1 scaffolds 758:766 reinforced alginate-hydroxyapatite (HA) aerogel scaffolds 710:766 reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications 710:787 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 5 64 theme aerogels 1009:1016 arg1 ageing 934:939 Gel ageing 930:939 Gel ageing in CaCl2 solutions 930:958 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 64 theme aerogels 1009:1016 arg1 intermediate 1036:1047 intermediate 1036:1047 intermediate 1036:1047 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 64 theme aerogels 1009:1016 arg1 strategies 1083:1092 post-processing reinforcement strategies 1053:1092 post-processing reinforcement strategies 1053:1092 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 64 theme aerogels 1009:1016 arg1 GA 980:981 GA 980:981 GA 980:981 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 64 theme aerogels 1009:1016 arg1 crosslinking 993:1004 glutaraldehyde (GA) chemical crosslinking 964:1004 glutaraldehyde (GA) chemical crosslinking of aerogels 964:1016 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 9 65 with endowed 1602:1608 arg1 bioactivity 1620:1630 high bioactivity 1615:1630 high bioactivity that is dependent on the HA content 1615:1666 The obtained aerogels were dual porous, bio- and hemocompatible, as well as endowed with high bioactivity that is dependent on the HA content. 35335542 1 66 dep three-dimensional 117:133 arg1 3D 136:137 3D 136:137 3D 136:137 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 10 67 theme physicochemical 1729:1743 arg1 performance 1745:1755 the physicochemical performance 1725:1755 the physicochemical performance of advanced biomaterials and their sterilization 1725:1804 This work is a step forward towards the optimization of the physicochemical performance of advanced biomaterials and their sterilization. 35335542 9 68 theme HA 1657:1658 arg1 content 1660:1666 the HA content 1653:1666 the HA content 1653:1666 The obtained aerogels were dual porous, bio- and hemocompatible, as well as endowed with high bioactivity that is dependent on the HA content. 35335542 8 69 theme post-sterilization 1455:1472 arg1 treatment 1474:1482 scCO2-based post-sterilization treatment 1443:1482 scCO2-based post-sterilization treatment 1443:1482 The impact of scCO2-based post-sterilization treatment on scaffold properties was also assessed. 35335542 0 70 theme Crosslinked 17:27 arg1 Aerogel 41:47 3D-Printed, Dual Crosslinked and Sterile Aerogel 0:47 3D-Printed, Dual Crosslinked and Sterile Aerogel 0:47 3D-Printed, Dual Crosslinked and Sterile Aerogel Scaffolds for Bone Tissue Engineering. 35335542 4 71 theme BTE 772:774 arg1 applications 776:787 BTE applications 772:787 BTE applications 772:787 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 10 72 theme biomaterials 1769:1780 arg1 performance 1745:1755 the physicochemical performance 1725:1755 the physicochemical performance of advanced biomaterials and their sterilization 1725:1804 This work is a step forward towards the optimization of the physicochemical performance of advanced biomaterials and their sterilization. 35335542 0 73 theme Sterile 33:39 arg1 Aerogel 41:47 3D-Printed, Dual Crosslinked and Sterile Aerogel 0:47 3D-Printed, Dual Crosslinked and Sterile Aerogel 0:47 3D-Printed, Dual Crosslinked and Sterile Aerogel Scaffolds for Bone Tissue Engineering. 35335542 1 74 theme bone 298:301 arg1 engineering 310:320 bone tissue engineering 298:320 bone tissue engineering (BTE) 298:326 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 1 74 theme bone 298:301 arg1 BTE 323:325 BTE 323:325 BTE 323:325 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 5 75 theme post-processing 1053:1067 arg1 ageing 934:939 Gel ageing 930:939 Gel ageing in CaCl2 solutions 930:958 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 75 theme post-processing 1053:1067 arg1 strategies 1083:1092 post-processing reinforcement strategies 1053:1092 post-processing reinforcement strategies 1053:1092 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 5 75 theme post-processing 1053:1067 arg1 crosslinking 993:1004 glutaraldehyde (GA) chemical crosslinking 964:1004 glutaraldehyde (GA) chemical crosslinking of aerogels 964:1016 Gel ageing in CaCl2 solutions and glutaraldehyde (GA) chemical crosslinking of aerogels were performed as intermediate and post-processing reinforcement strategies to achieve highly crosslinked aerogel scaffolds. 35335542 4 76 theme extrusion-based 836:850 arg1 drying 890:895 extrusion-based 3D-printing and supercritical CO2 gel drying 836:895 extrusion-based 3D-printing and supercritical CO2 gel drying 836:895 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 2 77 theme functional 411:420 arg1 scaffolds 437:445 functional nanostructured scaffolds 411:445 functional nanostructured scaffolds from polysaccharides 411:466 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 7 78 theme cell 1369:1372 arg1 viability 1374:1382 cell viability 1369:1382 cell viability 1369:1382 The biological evaluation of the aerogel scaffolds was performed regarding cell viability, hemolytic activity and bioactivity for BTE. 35335542 2 79 theme personalized 481:492 arg1 geometry 494:501 personalized geometry 481:501 personalized geometry 481:501 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 1 80 theme hydrogel 140:147 arg1 scaffolds 149:157 bioactive three-dimensional (3D) hydrogel scaffolds 107:157 bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) 107:246 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 2 81 theme 3D-printing 329:339 arg1 technology 341:350 3D-printing technology 329:350 3D-printing technology combined with aerogel processing 329:383 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 1 82 from fabrication 92:102 arg1 materials 178:186 biocompatible materials 164:186 biocompatible materials with a complex inner structure (mesoporous and macroporous) 164:246 The fabrication of bioactive three-dimensional (3D) hydrogel scaffolds from biocompatible materials with a complex inner structure (mesoporous and macroporous) and highly interconnected porosity is crucial for bone tissue engineering (BTE). 35335542 0 83 dep Crosslinked 17:27 arg1 Dual 12:15 Dual 12:15 Dual 12:15 3D-Printed, Dual Crosslinked and Sterile Aerogel Scaffolds for Bone Tissue Engineering. 35335542 2 84 from fabrication 396:406 arg1 polysaccharides 452:466 polysaccharides 452:466 polysaccharides 452:466 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 35335542 4 85 theme dual 808:811 arg1 strategy 813:820 a dual strategy 806:820 a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step 806:927 In this work, reinforced alginate-hydroxyapatite (HA) aerogel scaffolds for BTE applications were obtained by a dual strategy that combines extrusion-based 3D-printing and supercritical CO2 gel drying with an extra crosslinking step. 35335542 8 86 from impact 1433:1438 arg1 properties 1496:1505 scaffold properties 1487:1505 scaffold properties 1487:1505 The impact of scCO2-based post-sterilization treatment on scaffold properties was also assessed. 35335542 7 87 theme scaffolds 1335:1343 arg1 evaluation 1309:1318 The biological evaluation 1294:1318 The biological evaluation of the aerogel scaffolds 1294:1343 The biological evaluation of the aerogel scaffolds was performed regarding cell viability, hemolytic activity and bioactivity for BTE. 35335542 2 88 theme aerogel 366:372 arg1 processing 374:383 aerogel processing 366:383 aerogel processing 366:383 3D-printing technology combined with aerogel processing allows the fabrication of functional nanostructured scaffolds from polysaccharides for BTE with personalized geometry, porosity and composition. 37282963 3 0 theme partial 802:808 arg1 squares 816:822 partial least squares 802:822 partial least squares discriminant analysis 802:844 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 1 1 theme low-temperature 332:346 arg1 drying 356:361 high-or low-temperature hot air drying 324:361 high-or low-temperature hot air drying(HTHAD, LTHAD) 324:375 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 1 theme low-temperature 332:346 arg1 LTHAD 370:374 LTHAD 370:374 LTHAD 370:374 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 2 theme ulmoides 219:226 arg1 quality 183:189 the quality 179:189 the quality of male flowers of Eucommia ulmoides(MFOEU) 179:233 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 7 3 theme MFOEU 1285:1289 arg1 quality 1274:1280 the quality 1270:1280 the quality of MFOEU dried with different methods 1270:1318 According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. 37282963 1 4 theme air 352:354 arg1 drying 356:361 high-or low-temperature hot air drying 324:361 high-or low-temperature hot air drying(HTHAD, LTHAD) 324:375 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 4 theme air 352:354 arg1 LTHAD 370:374 LTHAD 370:374 LTHAD 370:374 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 2 5 theme flavonoid 454:462 arg1 color 441:445 The color 437:445 The color 437:445 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 aucubin 634:640 aucubin 634:640 aucubin 634:640 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 galuteolin 593:602 galuteolin 593:602 galuteolin 593:602 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 acid 562:565 geniposidic acid 550:565 geniposidic acid 550:565 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 indicators 680:689 the evaluation indicators 665:689 the evaluation indicators 665:689 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 rutin 568:572 rutin 568:572 rutin 568:572 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 diglucoside 617:627 pinoresinol diglucoside 605:627 pinoresinol diglucoside 605:627 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 geniposide 538:547 geniposide 538:547 geniposide 538:547 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 content 494:500 total polysaccharide content 473:500 total polysaccharide content 473:500 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 content 464:470 total flavonoid content 448:470 total flavonoid content 448:470 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 acid 587:590 chlorogenic acid 575:590 chlorogenic acid 575:590 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 5 theme flavonoid 454:462 arg1 components 519:528 main active components 507:528 main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU 507:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 0 6 theme flowers 56:62 arg1 quality 40:46 quality 40:46 quality of male flowers of Eucommia ulmoides 40:83 [Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition]. 37282963 4 7 theme MFOEU 964:968 arg1 color 955:959 the original color 942:959 the original color of MFOEU 942:968 The experimental results showed that VFD and DS basically kept the original color of MFOEU. 37282963 1 8 theme drying 161:166 arg1 methods 168:174 different drying methods 151:174 different drying methods 151:174 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 3 9 theme heat 869:872 arg1 map 874:876 clustering heat map 858:876 clustering heat map 858:876 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 2 10 theme pinoresinol 605:615 arg1 diglucoside 617:627 pinoresinol diglucoside 605:627 pinoresinol diglucoside 605:627 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 11 from acid 562:565 arg1 MFOEU 645:649 MFOEU 645:649 MFOEU 645:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 1 12 theme vacuum 297:302 arg1 drying 311:316 vacuum freeze drying 297:316 vacuum freeze drying(VFD) 297:321 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 12 theme vacuum 297:302 arg1 VFD 318:320 VFD 318:320 VFD 318:320 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 5 13 contain had 997:999 arg2 content 1008:1014 higher content 1001:1014 higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids 1001:1080 The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. 37282963 5 13 contain had 997:999 arg1 MFOEU 975:979 The MFOEU 971:979 The MFOEU treated with MD 971:995 The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. 37282963 2 14 from rutin 568:572 arg1 MFOEU 645:649 MFOEU 645:649 MFOEU 645:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 5 15 theme total 1019:1023 arg1 polysaccharides 1025:1039 total polysaccharides 1019:1039 total polysaccharides 1019:1039 The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. 37282963 10 16 from processing 1672:1681 arg1 areas 1700:1704 the producing areas 1686:1704 the producing areas 1686:1704 The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas. 37282963 0 17 theme male 51:54 arg1 flowers 56:62 male flowers 51:62 male flowers of Eucommia ulmoides 51:83 [Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition]. 37282963 1 18 from effects 140:146 arg1 quality 183:189 the quality 179:189 the quality of male flowers of Eucommia ulmoides(MFOEU) 179:233 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 6 19 contain had 1112:1114 arg1 MFOEU 1087:1091 The MFOEU 1083:1091 The MFOEU treated with LTHAD 1083:1110 The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. 37282963 6 19 contain had 1112:1114 arg2 content 1123:1129 higher content 1116:1129 higher content of total flavonoids 1116:1149 The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. 37282963 2 20 theme geniposidic 550:560 arg1 acid 562:565 geniposidic acid 550:565 geniposidic acid 550:565 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 5 21 theme iridoids 1073:1080 arg1 content 1008:1014 higher content 1001:1014 higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids 1001:1080 The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. 37282963 6 22 theme lower 1180:1184 arg1 content 1186:1192 lower content 1180:1192 lower content of active components 1180:1213 The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. 37282963 9 23 theme MFOEU 1527:1531 arg1 benefits 1515:1522 economic benefits 1506:1522 economic benefits 1506:1522 Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. 37282963 9 23 theme MFOEU 1527:1531 arg1 color 1476:1480 color 1476:1480 color 1476:1480 Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. 37282963 9 23 theme MFOEU 1527:1531 arg1 components 1490:1499 active components 1483:1499 active components 1483:1499 Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. 37282963 0 24 from [Effects 0:7 arg1 quality 40:46 quality 40:46 quality of male flowers of Eucommia ulmoides 40:83 [Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition]. 37282963 0 25 theme ulmoides 76:83 arg1 flowers 56:62 male flowers 51:62 male flowers of Eucommia ulmoides 51:83 [Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition]. 37282963 2 26 theme total 473:477 arg1 color 441:445 The color 437:445 The color 437:445 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 aucubin 634:640 aucubin 634:640 aucubin 634:640 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 galuteolin 593:602 galuteolin 593:602 galuteolin 593:602 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 acid 562:565 geniposidic acid 550:565 geniposidic acid 550:565 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 content 494:500 total polysaccharide content 473:500 total polysaccharide content 473:500 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 rutin 568:572 rutin 568:572 rutin 568:572 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 diglucoside 617:627 pinoresinol diglucoside 605:627 pinoresinol diglucoside 605:627 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 geniposide 538:547 geniposide 538:547 geniposide 538:547 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 indicators 680:689 the evaluation indicators 665:689 the evaluation indicators 665:689 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 content 464:470 total flavonoid content 448:470 total flavonoid content 448:470 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 acid 587:590 chlorogenic acid 575:590 chlorogenic acid 575:590 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 26 theme total 473:477 arg1 components 519:528 main active components 507:528 main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU 507:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 1 27 theme vacuum 404:409 arg1 drying 411:416 vacuum drying 404:416 vacuum drying(VD) 404:420 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 27 theme vacuum 404:409 arg1 VD 418:419 VD 418:419 VD 418:419 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 2 28 theme active 512:517 arg1 color 441:445 The color 437:445 The color 437:445 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 aucubin 634:640 aucubin 634:640 aucubin 634:640 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 galuteolin 593:602 galuteolin 593:602 galuteolin 593:602 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 acid 562:565 geniposidic acid 550:565 geniposidic acid 550:565 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 indicators 680:689 the evaluation indicators 665:689 the evaluation indicators 665:689 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 rutin 568:572 rutin 568:572 rutin 568:572 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 diglucoside 617:627 pinoresinol diglucoside 605:627 pinoresinol diglucoside 605:627 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 geniposide 538:547 geniposide 538:547 geniposide 538:547 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 content 494:500 total polysaccharide content 473:500 total polysaccharide content 473:500 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 content 464:470 total flavonoid content 448:470 total flavonoid content 448:470 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 acid 587:590 chlorogenic acid 575:590 chlorogenic acid 575:590 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 28 theme active 512:517 arg1 components 519:528 main active components 507:528 main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU 507:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 9 29 theme drying 1554:1559 arg1 method 1561:1566 the suitable drying method 1541:1566 the suitable drying method 1541:1566 Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. 37282963 9 29 theme drying 1554:1559 arg1 MD 1534:1535 MD 1534:1535 MD 1534:1535 Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. 37282963 0 30 theme different 12:20 arg1 methods 29:35 different drying methods 12:35 different drying methods 12:35 [Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition]. 37282963 5 31 theme higher 1001:1006 arg1 content 1008:1014 higher content 1001:1014 higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids 1001:1080 The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. 37282963 7 32 theme MD> 1342:1346 arg1 order 1333:1337 the order 1329:1337 the order of MD>HTHAD>VFD>LTHAD>DS>VD 1329:1380 According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. 37282963 3 33 theme entropy 746:752 arg1 method 761:766 entropy weight method 746:766 entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map 746:876 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 0 34 theme methods 29:35 arg1 [Effects 0:7 [Effects 0:7 [Effects of different drying methods on quality of male flowers of Eucommia ulmoides 0:83 [Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition]. 37282963 1 35 theme fresh 247:251 arg1 samples 259:265 fresh MFOEU samples 247:265 fresh MFOEU samples 247:265 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 3 36 theme index 788:792 arg1 method 794:799 color index method 782:799 color index method 782:799 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 9 37 dep color 1476:1480 arg1 the 1472:1474 the 1472:1474 the 1472:1474 Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. 37282963 6 38 theme components 1204:1213 arg1 content 1186:1192 lower content 1180:1192 lower content of active components 1180:1213 The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. 37282963 5 39 theme phenylpropanoids 1042:1057 arg1 content 1008:1014 higher content 1001:1014 higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids 1001:1080 The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. 37282963 7 40 theme different 1302:1310 arg1 methods 1312:1318 different methods 1302:1318 different methods 1302:1318 According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. 37282963 3 41 theme least 810:814 arg1 squares 816:822 partial least squares 802:822 partial least squares discriminant analysis 802:844 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 2 42 from diglucoside 617:627 arg1 MFOEU 645:649 MFOEU 645:649 MFOEU 645:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 8 43 theme drying 1428:1433 arg1 DS 1448:1449 DS 1448:1449 DS 1448:1449 Considering the color of MFOEU, the suitable drying methods were DS and VFD. 37282963 8 43 theme drying 1428:1433 arg1 methods 1435:1441 the suitable drying methods 1415:1441 the suitable drying methods 1415:1441 Considering the color of MFOEU, the suitable drying methods were DS and VFD. 37282963 7 44 dep MD> 1342:1346 arg1 VFD> 1357:1362 VFD> 1357:1362 MD>HTHAD>VFD>LTHAD>DS>VD 1342:1380 According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. 37282963 7 44 dep MD> 1342:1346 arg1 HTHAD> 1348:1355 HTHAD> 1348:1355 MD>HTHAD>VFD>LTHAD>DS>VD 1342:1380 According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. 37282963 7 44 dep MD> 1342:1346 arg1 DS> 1373:1377 DS> 1373:1377 MD>HTHAD>VFD>LTHAD>DS>VD 1342:1380 According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. 37282963 7 44 dep MD> 1342:1346 arg1 VD 1379:1380 VD 1379:1380 MD>HTHAD>VFD>LTHAD>DS>VD 1342:1380 According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. 37282963 7 44 dep MD> 1342:1346 arg1 LTHAD> 1364:1371 LTHAD> 1364:1371 MD>HTHAD>VFD>LTHAD>DS>VD 1342:1380 According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. 37282963 4 45 theme experimental 883:894 arg1 results 896:902 The experimental results 879:902 The experimental results 879:902 The experimental results showed that VFD and DS basically kept the original color of MFOEU. 37282963 1 46 theme Eucommia 210:217 arg1 ulmoides 219:226 Eucommia ulmoides 210:226 Eucommia ulmoides(MFOEU) 210:233 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 46 theme Eucommia 210:217 arg1 MFOEU 228:232 MFOEU 228:232 MFOEU 228:232 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 47 theme hot 348:350 arg1 drying 356:361 high-or low-temperature hot air drying 324:361 high-or low-temperature hot air drying(HTHAD, LTHAD) 324:375 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 47 theme hot 348:350 arg1 LTHAD 370:374 LTHAD 370:374 LTHAD 370:374 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 5 48 theme polysaccharides 1025:1039 arg1 content 1008:1014 higher content 1001:1014 higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids 1001:1080 The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. 37282963 3 49 theme discriminant 824:835 arg1 analysis 837:844 partial least squares discriminant analysis 802:844 partial least squares discriminant analysis 802:844 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 7 50 theme comprehensive 1244:1256 arg1 evaluation 1258:1267 comprehensive evaluation 1244:1267 comprehensive evaluation 1244:1267 According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. 37282963 8 51 theme MFOEU 1408:1412 arg1 color 1399:1403 the color 1395:1403 the color of MFOEU 1395:1412 Considering the color of MFOEU, the suitable drying methods were DS and VFD. 37282963 10 52 theme MFOEU 1666:1670 arg1 processing 1672:1681 MFOEU processing 1666:1681 MFOEU processing in the producing areas 1666:1704 The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas. 37282963 7 53 theme evaluation 1258:1267 arg1 results 1233:1239 the results 1229:1239 the results of comprehensive evaluation 1229:1267 According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. 37282963 2 54 theme chlorogenic 575:585 arg1 acid 587:590 chlorogenic acid 575:590 chlorogenic acid 575:590 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 10 55 theme methods 1654:1660 arg1 determination 1628:1640 the determination 1624:1640 the determination of suitable methods for MFOEU processing in the producing areas 1624:1704 The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas. 37282963 3 56 dep method 794:799 arg1 map 874:876 clustering heat map 858:876 clustering heat map 858:876 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 1 57 theme different 151:159 arg1 methods 168:174 different drying methods 151:174 different drying methods 151:174 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 2 58 theme total 448:452 arg1 color 441:445 The color 437:445 The color 437:445 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 aucubin 634:640 aucubin 634:640 aucubin 634:640 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 galuteolin 593:602 galuteolin 593:602 galuteolin 593:602 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 acid 562:565 geniposidic acid 550:565 geniposidic acid 550:565 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 indicators 680:689 the evaluation indicators 665:689 the evaluation indicators 665:689 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 rutin 568:572 rutin 568:572 rutin 568:572 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 diglucoside 617:627 pinoresinol diglucoside 605:627 pinoresinol diglucoside 605:627 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 geniposide 538:547 geniposide 538:547 geniposide 538:547 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 content 494:500 total polysaccharide content 473:500 total polysaccharide content 473:500 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 content 464:470 total flavonoid content 448:470 total flavonoid content 448:470 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 acid 587:590 chlorogenic acid 575:590 chlorogenic acid 575:590 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 58 theme total 448:452 arg1 components 519:528 main active components 507:528 main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU 507:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 3 59 theme clustering 858:867 arg1 map 874:876 clustering heat map 858:876 clustering heat map 858:876 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 2 60 from geniposide 538:547 arg1 MFOEU 645:649 MFOEU 645:649 MFOEU 645:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 10 61 theme producing 1690:1698 arg1 areas 1700:1704 the producing areas 1686:1704 the producing areas 1686:1704 The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas. 37282963 0 62 theme chemical 104:111 arg1 composition 113:123 chemical composition 104:123 chemical composition 104:123 [Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition]. 37282963 1 63 theme methods 168:174 arg1 effects 140:146 the effects 136:146 the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU) 136:233 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 4 64 theme original 946:953 arg1 color 955:959 the original color 942:959 the original color of MFOEU 942:968 The experimental results showed that VFD and DS basically kept the original color of MFOEU. 37282963 6 65 theme flavonoids 1140:1149 arg1 content 1123:1129 higher content 1116:1129 higher content of total flavonoids 1116:1149 The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. 37282963 1 66 theme freeze 304:309 arg1 drying 311:316 vacuum freeze drying 297:316 vacuum freeze drying(VFD) 297:321 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 66 theme freeze 304:309 arg1 VFD 318:320 VFD 318:320 VFD 318:320 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 9 67 theme active 1483:1488 arg1 components 1490:1499 active components 1483:1499 active components 1483:1499 Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. 37282963 6 68 contain had 1176:1178 arg2 content 1186:1192 lower content 1180:1192 lower content of active components 1180:1213 The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. 37282963 6 68 contain had 1176:1178 arg1 that 1155:1158 that 1155:1158 that 1155:1158 The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. 37282963 6 69 theme higher 1116:1121 arg1 content 1123:1129 higher content 1116:1129 higher content of total flavonoids 1116:1149 The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. 37282963 6 70 theme active 1197:1202 arg1 components 1204:1213 active components 1197:1213 active components 1197:1213 The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. 37282963 1 71 theme high-or 324:330 arg1 drying 356:361 high-or low-temperature hot air drying 324:361 high-or low-temperature hot air drying(HTHAD, LTHAD) 324:375 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 71 theme high-or 324:330 arg1 LTHAD 370:374 LTHAD 370:374 LTHAD 370:374 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 9 72 theme economic 1506:1513 arg1 benefits 1515:1522 economic benefits 1506:1522 economic benefits 1506:1522 Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. 37282963 0 73 theme Eucommia 67:74 arg1 ulmoides 76:83 Eucommia ulmoides 67:83 Eucommia ulmoides 67:83 [Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition]. 37282963 3 74 theme MFOEU 707:711 arg1 quality 696:702 The quality 692:702 The quality of MFOEU 692:711 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 2 75 theme polysaccharide 479:492 arg1 color 441:445 The color 437:445 The color 437:445 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 aucubin 634:640 aucubin 634:640 aucubin 634:640 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 galuteolin 593:602 galuteolin 593:602 galuteolin 593:602 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 acid 562:565 geniposidic acid 550:565 geniposidic acid 550:565 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 content 494:500 total polysaccharide content 473:500 total polysaccharide content 473:500 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 rutin 568:572 rutin 568:572 rutin 568:572 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 diglucoside 617:627 pinoresinol diglucoside 605:627 pinoresinol diglucoside 605:627 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 geniposide 538:547 geniposide 538:547 geniposide 538:547 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 indicators 680:689 the evaluation indicators 665:689 the evaluation indicators 665:689 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 content 464:470 total flavonoid content 448:470 total flavonoid content 448:470 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 acid 587:590 chlorogenic acid 575:590 chlorogenic acid 575:590 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 75 theme polysaccharide 479:492 arg1 components 519:528 main active components 507:528 main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU 507:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 76 from aucubin 634:640 arg1 MFOEU 645:649 MFOEU 645:649 MFOEU 645:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 9 77 theme suitable 1545:1552 arg1 method 1561:1566 the suitable drying method 1541:1566 the suitable drying method 1541:1566 Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. 37282963 9 77 theme suitable 1545:1552 arg1 MD 1534:1535 MD 1534:1535 MD 1534:1535 Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. 37282963 2 78 theme main 507:510 arg1 color 441:445 The color 437:445 The color 437:445 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 aucubin 634:640 aucubin 634:640 aucubin 634:640 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 galuteolin 593:602 galuteolin 593:602 galuteolin 593:602 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 acid 562:565 geniposidic acid 550:565 geniposidic acid 550:565 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 indicators 680:689 the evaluation indicators 665:689 the evaluation indicators 665:689 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 rutin 568:572 rutin 568:572 rutin 568:572 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 diglucoside 617:627 pinoresinol diglucoside 605:627 pinoresinol diglucoside 605:627 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 geniposide 538:547 geniposide 538:547 geniposide 538:547 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 content 494:500 total polysaccharide content 473:500 total polysaccharide content 473:500 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 content 464:470 total flavonoid content 448:470 total flavonoid content 448:470 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 acid 587:590 chlorogenic acid 575:590 chlorogenic acid 575:590 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 78 theme main 507:510 arg1 components 519:528 main active components 507:528 main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU 507:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 0 79 theme drying 22:27 arg1 methods 29:35 different drying methods 12:35 different drying methods 12:35 [Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition]. 37282963 3 80 theme weight 754:759 arg1 method 761:766 entropy weight method 746:766 entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map 746:876 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 10 81 theme study 1589:1593 arg1 results 1573:1579 The results 1569:1579 The results of this study 1569:1593 The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas. 37282963 1 82 theme flowers 199:205 arg1 quality 183:189 the quality 179:189 the quality of male flowers of Eucommia ulmoides(MFOEU) 179:233 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 83 from drying 272:277 arg1 drying 311:316 vacuum freeze drying 297:316 vacuum freeze drying(VFD) 297:321 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 83 from drying 272:277 arg1 MD 395:396 MD 395:396 MD 395:396 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 83 from drying 272:277 arg1 VD 418:419 VD 418:419 VD 418:419 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 83 from drying 272:277 arg1 DS 292:293 DS 292:293 DS 292:293 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 83 from drying 272:277 arg1 drying 356:361 high-or low-temperature hot air drying 324:361 high-or low-temperature hot air drying(HTHAD, LTHAD) 324:375 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 83 from drying 272:277 arg1 VFD 318:320 VFD 318:320 VFD 318:320 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 83 from drying 272:277 arg1 drying 388:393 microwave drying 378:393 microwave drying(MD) 378:397 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 83 from drying 272:277 arg1 drying 411:416 vacuum drying 404:416 vacuum drying(VD) 404:420 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 83 from drying 272:277 arg1 shade 286:290 the shade 282:290 the shade(DS) 282:294 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 83 from drying 272:277 arg1 LTHAD 370:374 LTHAD 370:374 LTHAD 370:374 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 84 theme MFOEU 253:257 arg1 samples 259:265 fresh MFOEU samples 247:265 fresh MFOEU samples 247:265 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 6 85 theme total 1134:1138 arg1 flavonoids 1140:1149 total flavonoids 1134:1149 total flavonoids 1134:1149 The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. 37282963 2 86 from acid 587:590 arg1 MFOEU 645:649 MFOEU 645:649 MFOEU 645:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 1 87 theme microwave 378:386 arg1 MD 395:396 MD 395:396 MD 395:396 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 1 87 theme microwave 378:386 arg1 drying 388:393 microwave drying 378:393 microwave drying(MD) 378:397 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 8 88 theme suitable 1419:1426 arg1 DS 1448:1449 DS 1448:1449 DS 1448:1449 Considering the color of MFOEU, the suitable drying methods were DS and VFD. 37282963 8 88 theme suitable 1419:1426 arg1 methods 1435:1441 the suitable drying methods 1415:1441 the suitable drying methods 1415:1441 Considering the color of MFOEU, the suitable drying methods were DS and VFD. 37282963 3 89 theme color 782:786 arg1 method 794:799 color index method 782:799 color index method 782:799 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 10 90 theme reference 1604:1612 arg1 value 1614:1618 a reference value 1602:1618 a reference value for the determination of suitable methods for MFOEU processing in the producing areas 1602:1704 The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas. 37282963 2 91 from galuteolin 593:602 arg1 MFOEU 645:649 MFOEU 645:649 MFOEU 645:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 1 92 theme male 194:197 arg1 flowers 199:205 male flowers 194:205 male flowers 194:205 To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. 37282963 3 93 theme squares 816:822 arg1 analysis 837:844 partial least squares discriminant analysis 802:844 partial least squares discriminant analysis 802:844 The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. 37282963 2 94 theme evaluation 669:678 arg1 color 441:445 The color 437:445 The color 437:445 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 aucubin 634:640 aucubin 634:640 aucubin 634:640 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 galuteolin 593:602 galuteolin 593:602 galuteolin 593:602 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 acid 562:565 geniposidic acid 550:565 geniposidic acid 550:565 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 indicators 680:689 the evaluation indicators 665:689 the evaluation indicators 665:689 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 rutin 568:572 rutin 568:572 rutin 568:572 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 diglucoside 617:627 pinoresinol diglucoside 605:627 pinoresinol diglucoside 605:627 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 geniposide 538:547 geniposide 538:547 geniposide 538:547 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 content 494:500 total polysaccharide content 473:500 total polysaccharide content 473:500 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 content 464:470 total flavonoid content 448:470 total flavonoid content 448:470 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 acid 587:590 chlorogenic acid 575:590 chlorogenic acid 575:590 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 2 94 theme evaluation 669:678 arg1 components 519:528 main active components 507:528 main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU 507:649 The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. 37282963 10 95 theme suitable 1645:1652 arg1 methods 1654:1660 suitable methods 1645:1660 suitable methods for MFOEU processing in the producing areas 1645:1704 The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas. 37282963 5 96 theme lignans 1060:1066 arg1 content 1008:1014 higher content 1001:1014 higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids 1001:1080 The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. 36386925 2 0 theme DEAE-52 358:364 arg1 cellulose 366:374 DEAE-52 cellulose 358:374 DEAE-52 cellulose 358:374 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 4 1 theme -linked 836:842 arg1 β-Galp- 985:991 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 985:991 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 2 link -linked 946:952 arg1 β-Arap- 888:894 β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, 888:974 β-Arap- 888:894 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 3 theme T-Manp-linked 809:821 arg1 β-Galp- 985:991 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 985:991 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 2 4 used utilized 270:277 arg2 striolatum 255:264 Z. striolatum 252:264 Z. striolatum 252:264 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 5 5 theme bacteria 1248:1255 arg1 growth 1227:1232 the growth 1223:1232 the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine 1223:1324 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 6 6 theme imbalanced 1348:1357 arg1 structure 1365:1373 the imbalanced flora structure 1344:1373 the imbalanced flora structure due to high-fat diet to normal 1344:1404 It also restored the imbalanced flora structure due to high-fat diet to normal. 36386925 1 7 theme gut 208:210 arg1 microbiota 212:221 gut microbiota 208:221 gut microbiota 208:221 To investigate a polysaccharide from Zingiber striolatum favorably modulates gut microbiota in mice fed a high-fat diet. 36386925 4 8 theme -linked 857:863 arg1 β-Galp- 985:991 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 985:991 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 9 theme β-T-Xylp-linked 959:973 arg1 β-Arap- 888:894 β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, 888:974 β-Arap- 888:894 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 2 10 theme polysaccharide 300:313 arg1 CZSP 315:318 the crude polysaccharide CZSP 290:318 the crude polysaccharide CZSP 290:318 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 5 11 from structure 1149:1157 arg1 mice 1204:1207 obese mice 1198:1207 obese mice 1198:1207 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 7 12 theme imbalanced 1428:1437 arg1 structure 1445:1453 the imbalanced flora structure 1424:1453 the imbalanced flora structure due to high-fat diet to normal 1424:1484 It also restored the imbalanced flora structure due to high-fat diet to normal. 36386925 4 13 theme -linked 997:1003 arg1 β-Galp- 985:991 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 985:991 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 2 14 theme Z. 252:253 arg1 striolatum 255:264 Z. striolatum 252:264 Z. striolatum 252:264 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 1 15 from striolatum 177:186 arg1 polysaccharide 148:161 a polysaccharide 146:161 a polysaccharide from Zingiber striolatum 146:186 To investigate a polysaccharide from Zingiber striolatum favorably modulates gut microbiota in mice fed a high-fat diet. 36386925 4 16 link -linked 925:931 arg1 β-Arap- 888:894 β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, 888:974 β-Arap- 888:894 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 5 17 theme intervention 1076:1087 arg1 experiments 1089:1099 the intervention experiments 1072:1099 the intervention experiments 1072:1099 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 1 18 theme Zingiber 168:175 arg1 striolatum 177:186 Zingiber striolatum 168:186 Zingiber striolatum 168:186 To investigate a polysaccharide from Zingiber striolatum favorably modulates gut microbiota in mice fed a high-fat diet. 36386925 8 19 dep induced 1581:1587 arg1 indicates 1604:1612 indicates 1604:1612 indicates that it can be further exploited as a natural functional food resource 1604:1683 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 0 20 theme microbiota 93:102 arg1 composition 104:114 gut microbiota composition 89:114 gut microbiota composition in obese mice 89:128 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 8 21 theme natural 1652:1658 arg1 resource 1676:1683 a natural functional food resource 1650:1683 a natural functional food resource 1650:1683 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 8 21 theme natural 1652:1658 arg1 it 1619:1620 it 1619:1620 it 1619:1620 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 4 22 theme -linked 879:885 arg1 β-Galp- 985:991 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 985:991 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 0 23 from striolatum 59:68 arg1 polysaccharide 30:43 polysaccharide 30:43 polysaccharide from Zingiber striolatum 30:68 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 0 23 from striolatum 59:68 arg1 characteristics 11:25 Structural characteristics 0:25 Structural characteristics of polysaccharide from Zingiber striolatum 0:68 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 0 23 from striolatum 59:68 arg1 effects 78:84 its effects 74:84 its effects on gut microbiota composition in obese mice 74:128 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 5 24 theme Firmicutes 1166:1175 arg1 structure 1149:1157 the intestinal flora structure 1128:1157 the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice 1128:1207 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 8 25 theme food 1671:1674 arg1 resource 1676:1683 a natural functional food resource 1650:1683 a natural functional food resource 1650:1683 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 8 25 theme food 1671:1674 arg1 it 1619:1620 it 1619:1620 it 1619:1620 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 4 26 link -linked 900:906 arg1 β-Arap- 888:894 β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, 888:974 β-Arap- 888:894 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 5 27 theme Bacteroidetes 1181:1193 arg1 structure 1149:1157 the intestinal flora structure 1128:1157 the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice 1128:1207 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 0 28 theme Structural 0:9 arg1 characteristics 11:25 Structural characteristics 0:25 Structural characteristics of polysaccharide from Zingiber striolatum 0:68 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 4 29 theme -linked 925:931 arg1 β-Arap- 888:894 β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, 888:974 β-Arap- 888:894 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 30 theme main 1043:1046 arg1 α-GalpA- 1009:1016 α-GalpA-(1,4)-linked 1009:1028 α-GalpA-(1,4)-linked 1009:1028 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 30 theme main 1043:1046 arg1 linkage 1048:1054 the main linkage 1039:1054 the main linkage 1039:1054 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 5 31 theme flora 1143:1147 arg1 structure 1149:1157 the intestinal flora structure 1128:1157 the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice 1128:1207 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 2 32 theme strioatum 438:446 arg1 ZSPP-1 471:476 ZSPP-1 471:476 ZSPP-1 471:476 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 2 32 theme strioatum 438:446 arg1 polysaccharide-1 453:468 the novel polysaccharide Zingiber strioatum pure polysaccharide-1 404:468 the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1) 404:477 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 4 33 dep include 801:807 arg1 that 768:771 that 768:771 that 768:771 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 34 theme -linked 900:906 arg1 β-Arap- 888:894 β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, 888:974 β-Arap- 888:894 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 8 35 theme considerable 1529:1540 arg1 advantage 1542:1550 a considerable advantage 1527:1550 a considerable advantage 1527:1550 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 4 36 theme linkage 777:783 arg1 types 795:799 the linkage structure types 773:799 the linkage structure types 773:799 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 37 link -linked 997:1003 arg1 β-Galp- 985:991 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 985:991 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 2 38 theme polysaccharide 414:427 arg1 ZSPP-1 471:476 ZSPP-1 471:476 ZSPP-1 471:476 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 2 38 theme polysaccharide 414:427 arg1 polysaccharide-1 453:468 the novel polysaccharide Zingiber strioatum pure polysaccharide-1 404:468 the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1) 404:477 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 4 39 link -linked 879:885 arg1 β-Galp- 985:991 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 985:991 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 3 40 theme molecular 628:636 arg1 weight 638:643 an average molecular weight 617:643 an average molecular weight of 1.57 × 106 Da 617:660 ZSPP-1 was an acidic heteroglycan made up of galactose, mannose, glucose, xylose, arabinose, glucuronic acid, and galacturonic acid with an average molecular weight of 1.57 × 106 Da. 36386925 4 41 theme -linked 946:952 arg1 β-Arap- 888:894 β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, 888:974 β-Arap- 888:894 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 3 42 theme Da 659:660 arg1 weight 638:643 an average molecular weight 617:643 an average molecular weight of 1.57 × 106 Da 617:660 ZSPP-1 was an acidic heteroglycan made up of galactose, mannose, glucose, xylose, arabinose, glucuronic acid, and galacturonic acid with an average molecular weight of 1.57 × 106 Da. 36386925 3 43 theme × 653:653 arg1 Da 659:660 1.57 × 106 Da 648:660 1.57 × 106 Da 648:660 ZSPP-1 was an acidic heteroglycan made up of galactose, mannose, glucose, xylose, arabinose, glucuronic acid, and galacturonic acid with an average molecular weight of 1.57 × 106 Da. 36386925 5 44 theme obese 1198:1202 arg1 mice 1204:1207 obese mice 1198:1207 obese mice 1198:1207 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 2 45 theme Sephadex 380:387 arg1 G-150 389:393 Sephadex G-150 380:393 Sephadex G-150 380:393 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 4 46 from β-Arap- 888:894 arg1 which 979:983 which 979:983 which 979:983 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 47 link -linked 857:863 arg1 β-Galp- 985:991 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 985:991 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 48 link β-T-Xylp-linked 959:973 arg1 β-Arap- 888:894 β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, 888:974 β-Arap- 888:894 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 8 49 theme striolatum 1490:1499 arg1 polysaccharides 1501:1515 Z. striolatum polysaccharides 1487:1515 Z. striolatum polysaccharides 1487:1515 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 2 50 theme crude 294:298 arg1 CZSP 315:318 the crude polysaccharide CZSP 290:318 the crude polysaccharide CZSP 290:318 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 6 51 theme high-fat 1382:1389 arg1 diet 1391:1394 high-fat diet 1382:1394 high-fat diet to normal 1382:1404 It also restored the imbalanced flora structure due to high-fat diet to normal. 36386925 6 52 theme due 1375:1377 arg1 structure 1365:1373 the imbalanced flora structure 1344:1373 the imbalanced flora structure due to high-fat diet to normal 1344:1404 It also restored the imbalanced flora structure due to high-fat diet to normal. 36386925 4 53 link -linked 836:842 arg1 β-Galp- 985:991 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 985:991 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 5 54 theme beneficial 1237:1246 arg1 bacteria 1248:1255 beneficial bacteria 1237:1255 beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine 1237:1324 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 5 54 theme beneficial 1237:1246 arg1 Akkermansia 1265:1275 Akkermansia 1265:1275 Akkermansia 1265:1275 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 5 54 theme beneficial 1237:1246 arg1 Bacteroides 1297:1307 Bacteroides 1297:1307 Bacteroides 1297:1307 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 5 54 theme beneficial 1237:1246 arg1 Lactobacillus 1278:1290 Lactobacillus 1278:1290 Lactobacillus 1278:1290 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 6 55 theme flora 1359:1363 arg1 structure 1365:1373 the imbalanced flora structure 1344:1373 the imbalanced flora structure due to high-fat diet to normal 1344:1404 It also restored the imbalanced flora structure due to high-fat diet to normal. 36386925 7 56 theme high-fat 1462:1469 arg1 diet 1471:1474 high-fat diet 1462:1474 high-fat diet to normal 1462:1484 It also restored the imbalanced flora structure due to high-fat diet to normal. 36386925 8 57 theme high-fat 1567:1574 arg1 diet 1576:1579 high-fat diet 1567:1579 high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource 1567:1683 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 7 58 theme due 1455:1457 arg1 structure 1445:1453 the imbalanced flora structure 1424:1453 the imbalanced flora structure due to high-fat diet to normal 1424:1484 It also restored the imbalanced flora structure due to high-fat diet to normal. 36386925 7 59 theme flora 1439:1443 arg1 structure 1445:1453 the imbalanced flora structure 1424:1453 the imbalanced flora structure due to high-fat diet to normal 1424:1484 It also restored the imbalanced flora structure due to high-fat diet to normal. 36386925 0 60 from effects 78:84 arg1 composition 104:114 gut microbiota composition 89:114 gut microbiota composition in obese mice 89:128 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 0 60 from effects 78:84 arg1 striolatum 59:68 Zingiber striolatum 50:68 Zingiber striolatum 50:68 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 4 61 link T-Manp-linked 809:821 arg1 β-Galp- 985:991 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 985:991 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 3 62 theme glucuronic 573:582 arg1 acid 584:587 glucuronic acid 573:587 glucuronic acid 573:587 ZSPP-1 was an acidic heteroglycan made up of galactose, mannose, glucose, xylose, arabinose, glucuronic acid, and galacturonic acid with an average molecular weight of 1.57 × 106 Da. 36386925 4 63 theme ZSPP-1 680:685 arg1 structure 667:675 The structure 663:675 The structure of ZSPP-1 663:685 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 64 dep β-Arap- 888:894 arg1 1,4 896:898 1,4 896:898 1,4 896:898 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 0 65 from composition 104:114 arg1 mice 125:128 obese mice 119:128 obese mice 119:128 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 5 66 from Bacteroidetes 1181:1193 arg1 mice 1204:1207 obese mice 1198:1207 obese mice 1198:1207 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 3 67 theme galacturonic 594:605 arg1 acid 607:610 galacturonic acid 594:610 galacturonic acid 594:610 ZSPP-1 was an acidic heteroglycan made up of galactose, mannose, glucose, xylose, arabinose, glucuronic acid, and galacturonic acid with an average molecular weight of 1.57 × 106 Da. 36386925 5 68 from Firmicutes 1166:1175 arg1 mice 1204:1207 obese mice 1198:1207 obese mice 1198:1207 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 0 69 theme gut 89:91 arg1 composition 104:114 gut microbiota composition 89:114 gut microbiota composition in obese mice 89:128 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 4 70 dep β-Galp- 985:991 arg1 β-Arap- 888:894 β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, 888:974 β-Arap- 888:894 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 4 70 dep β-Galp- 985:991 arg1 β-Galp- 845:851 T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp- 809:991 β-Galp- 845:851 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 0 71 from characteristics 11:25 arg1 composition 104:114 gut microbiota composition 89:114 gut microbiota composition in obese mice 89:128 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 0 71 from characteristics 11:25 arg1 striolatum 59:68 Zingiber striolatum 50:68 Zingiber striolatum 50:68 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 5 72 theme experiments 1089:1099 arg1 results 1061:1067 The results 1057:1067 The results of the intervention experiments 1057:1099 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 4 73 theme NMR 730:732 arg1 analysis 734:741 methylation and NMR analysis 714:741 analysis 734:741 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 0 74 theme obese 119:123 arg1 mice 125:128 obese mice 119:128 obese mice 119:128 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 5 75 from mice 1204:1207 arg1 structure 1149:1157 the intestinal flora structure 1128:1157 the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice 1128:1207 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 8 76 theme functional 1660:1669 arg1 resource 1676:1683 a natural functional food resource 1650:1683 a natural functional food resource 1650:1683 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 8 76 theme functional 1660:1669 arg1 it 1619:1620 it 1619:1620 it 1619:1620 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 5 77 theme intestinal 1132:1141 arg1 structure 1149:1157 the intestinal flora structure 1128:1157 the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice 1128:1207 The results of the intervention experiments showed that ZSPP-1 changed the intestinal flora structure of the Firmicutes and Bacteroidetes in obese mice, and promoted the growth of beneficial bacteria such as Akkermansia, Lactobacillus, and Bacteroides in the intestine. 36386925 0 78 theme polysaccharide 30:43 arg1 characteristics 11:25 Structural characteristics 0:25 Structural characteristics of polysaccharide from Zingiber striolatum 0:68 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 0 78 theme polysaccharide 30:43 arg1 effects 78:84 its effects 74:84 its effects on gut microbiota composition in obese mice 74:128 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 2 79 theme pure 448:451 arg1 ZSPP-1 471:476 ZSPP-1 471:476 ZSPP-1 471:476 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 2 79 theme pure 448:451 arg1 polysaccharide-1 453:468 the novel polysaccharide Zingiber strioatum pure polysaccharide-1 404:468 the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1) 404:477 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 4 80 theme methylation 714:724 arg1 analysis 734:741 methylation and NMR analysis 714:741 analysis 734:741 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 2 81 theme Zingiber 429:436 arg1 ZSPP-1 471:476 ZSPP-1 471:476 ZSPP-1 471:476 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 2 81 theme Zingiber 429:436 arg1 polysaccharide-1 453:468 the novel polysaccharide Zingiber strioatum pure polysaccharide-1 404:468 the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1) 404:477 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 0 82 theme Zingiber 50:57 arg1 striolatum 59:68 Zingiber striolatum 50:68 Zingiber striolatum 50:68 Structural characteristics of polysaccharide from Zingiber striolatum and its effects on gut microbiota composition in obese mice. 36386925 3 83 theme average 620:626 arg1 weight 638:643 an average molecular weight 617:643 an average molecular weight of 1.57 × 106 Da 617:660 ZSPP-1 was an acidic heteroglycan made up of galactose, mannose, glucose, xylose, arabinose, glucuronic acid, and galacturonic acid with an average molecular weight of 1.57 × 106 Da. 36386925 2 84 theme novel 408:412 arg1 ZSPP-1 471:476 ZSPP-1 471:476 ZSPP-1 471:476 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 2 84 theme novel 408:412 arg1 polysaccharide-1 453:468 the novel polysaccharide Zingiber strioatum pure polysaccharide-1 404:468 the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1) 404:477 Z. striolatum was utilized to extract the crude polysaccharide CZSP, which was subsequently refined using DEAE-52 cellulose and Sephadex G-150 to yield the novel polysaccharide Zingiber strioatum pure polysaccharide-1 (ZSPP-1). 36386925 4 85 theme structure 785:793 arg1 types 795:799 the linkage structure types 773:799 the linkage structure types 773:799 The structure of ZSPP-1 was investigated by FT-IR, methylation and NMR analysis, and the results denoted that the linkage structure types include T-Manp-linked, β-Xylp-(1,2)-linked, β-Galp-(1,4)-linked, α-GlcpA-(1,6)-linked, β-Arap-(1,4)-linked, α-Glcp-(1,3,4,6)-linked, α-Glcp-(1,2)-linked, and β-T-Xylp-linked, in which β-Galp-(1,4)-linked and α-GalpA-(1,4)-linked might be the main linkage. 36386925 3 86 theme acidic 494:499 arg1 heteroglycan 501:512 an acidic heteroglycan 491:512 an acidic heteroglycan made up of galactose, mannose, glucose, xylose, arabinose, glucuronic acid, and galacturonic acid with an average molecular weight of 1.57 × 106 Da 491:660 ZSPP-1 was an acidic heteroglycan made up of galactose, mannose, glucose, xylose, arabinose, glucuronic acid, and galacturonic acid with an average molecular weight of 1.57 × 106 Da. 36386925 3 86 theme acidic 494:499 arg1 ZSPP-1 480:485 ZSPP-1 480:485 ZSPP-1 480:485 ZSPP-1 was an acidic heteroglycan made up of galactose, mannose, glucose, xylose, arabinose, glucuronic acid, and galacturonic acid with an average molecular weight of 1.57 × 106 Da. 36386925 8 87 theme Z. 1487:1488 arg1 polysaccharides 1501:1515 Z. striolatum polysaccharides 1487:1515 Z. striolatum polysaccharides 1487:1515 Z. striolatum polysaccharides presented a considerable advantage in alleviating high-fat diet induced obesity, which indicates that it can be further exploited as a natural functional food resource. 36386925 1 88 theme high-fat 237:244 arg1 diet 246:249 a high-fat diet 235:249 a high-fat diet 235:249 To investigate a polysaccharide from Zingiber striolatum favorably modulates gut microbiota in mice fed a high-fat diet. 35934380 6 0 theme several 891:897 arg1 steps 899:903 several steps 891:903 several steps that involve advanced functions such as heating and mixing with organic solvents 891:984 Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. 35934380 0 1 theme sample 28:33 arg1 treatment 35:43 glycan sample treatment 21:43 glycan sample treatment 21:43 Lab-in-droplet: From glycan sample treatment toward diagnostic screening of congenital disorders of glycosylation. 35934380 9 2 theme Lab-in-Droplet 1420:1433 arg1 superiority 1400:1410 the superiority 1396:1410 the superiority of this Lab-in-Droplet over the conventional batchwise protocol 1396:1474 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 10 3 with platform 1675:1682 arg1 protocol 1711:1718 the developed droplet protocol 1689:1718 the developed droplet protocol 1689:1718 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 4 4 theme droplet 586:592 arg1 setups 594:599 previous droplet setups 577:599 previous droplet setups 577:599 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 10 5 link N-linked 1757:1764 arg1 glycans 1766:1772 N-linked glycans 1757:1772 N-linked glycans 1757:1772 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 8 6 theme N-linked 1211:1218 arg1 oligosaccharides 1220:1235 N-linked oligosaccharides 1211:1235 N-linked oligosaccharides from Human Immuglobulin G 1211:1261 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 9 7 theme batchwise 1457:1465 arg1 protocol 1467:1474 the conventional batchwise protocol 1440:1474 the conventional batchwise protocol 1440:1474 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 6 8 theme confined 847:854 arg1 microreactors 856:868 confined microreactors 847:868 confined microreactors 847:868 Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. 35934380 2 9 theme glycoprotein 312:323 arg1 treatment 291:299 the sample treatment 280:299 the sample treatment of a given glycoprotein to profile its N-glycans 280:348 Several operations are required for the sample treatment of a given glycoprotein to profile its N-glycans. 35934380 6 10 with functions 927:935 arg1 solvents 977:984 organic solvents 969:984 organic solvents 969:984 Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. 35934380 8 11 theme Immuglobulin 1248:1259 arg1 G 1261:1261 Human Immuglobulin G 1242:1261 Human Immuglobulin G 1242:1261 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 10 12 theme disorders 1847:1855 arg1 screening 1823:1831 diagnostic screening 1812:1831 diagnostic screening of congenital disorders of glycosylation 1812:1872 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 7 13 theme complex 989:995 arg1 feasible 1037:1044 feasible 1037:1044 feasible 1037:1044 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 7 13 theme complex 989:995 arg1 protocol 1014:1021 A complex sample treatment protocol 987:1021 A complex sample treatment protocol that has been feasible so far only in batchwise mode 987:1074 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 9 14 theme reagent 1495:1501 arg1 consumption 1503:1513 10-fold less reagent consumption 1482:1513 10-fold less reagent consumption 1482:1513 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 6 15 theme advanced 918:925 arg1 functions 927:935 advanced functions 918:935 advanced functions such as heating 918:951 Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. 35934380 6 15 theme advanced 918:925 arg1 heating 945:951 heating 945:951 heating 945:951 Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. 35934380 5 16 theme tweezer 669:675 arg1 technology 677:686 The magnetic tweezer technology 656:686 The magnetic tweezer technology 656:686 The magnetic tweezer technology was employed to manipulate (capture and release) coated magnetic beads used as analyte cargos over droplets. 35934380 9 17 theme less 1523:1526 arg1 time 1528:1531 3-fold less time 1516:1531 3-fold less time 1516:1531 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 5 18 theme magnetic 744:751 arg1 beads 753:757 (capture and release) coated magnetic beads 715:757 (capture and release) coated magnetic beads used as analyte cargos over droplets 715:794 The magnetic tweezer technology was employed to manipulate (capture and release) coated magnetic beads used as analyte cargos over droplets. 35934380 10 19 theme glycosylation 1860:1872 arg1 disorders 1847:1855 congenital disorders 1836:1855 congenital disorders of glycosylation 1836:1872 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 1 20 theme new 142:144 arg1 platform 167:174 a new microfluidic droplet platform 140:174 a new microfluidic droplet platform 140:174 We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. 35934380 8 21 theme capillary 1312:1320 arg1 electrophoresis 1322:1336 capillary electrophoresis 1312:1336 capillary electrophoresis with laser induced fluorescent detection 1312:1377 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 0 22 theme congenital 76:85 arg1 disorders 87:95 congenital disorders 76:95 congenital disorders of glycosylation 76:112 Lab-in-droplet: From glycan sample treatment toward diagnostic screening of congenital disorders of glycosylation. 35934380 1 23 theme droplet 159:165 arg1 platform 167:174 a new microfluidic droplet platform 140:174 a new microfluidic droplet platform 140:174 We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. 35934380 6 24 theme organic 969:975 arg1 solvents 977:984 organic solvents 969:984 organic solvents 969:984 Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. 35934380 3 25 theme automatic 459:467 arg1 manner 469:474 an automatic manner 456:474 an automatic manner 456:474 In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. 35934380 8 26 theme induced 1349:1355 arg1 detection 1369:1377 laser induced fluorescent detection 1343:1377 laser induced fluorescent detection 1343:1377 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 4 27 from met 570:572 arg1 setups 594:599 previous droplet setups 577:599 previous droplet setups 577:599 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 9 28 theme labeling 1567:1574 arg1 yield 1576:1580 glycan labeling yield 1560:1580 glycan labeling yield 1560:1580 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 10 29 theme human 1788:1792 arg1 sera 1794:1797 human sera 1788:1797 human sera 1788:1797 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 7 30 from mode 1071:1074 arg1 feasible 1037:1044 feasible 1037:1044 feasible 1037:1044 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 7 30 from mode 1071:1074 arg1 protocol 1014:1021 A complex sample treatment protocol 987:1021 A complex sample treatment protocol that has been feasible so far only in batchwise mode 987:1074 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 8 31 dep release 1179:1185 arg1 analyze 1281:1287 analyze 1281:1287 analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection 1281:1377 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 10 32 theme developed 1693:1701 arg1 protocol 1711:1718 the developed droplet protocol 1689:1718 the developed droplet protocol 1689:1718 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 5 33 theme analyte 767:773 arg1 cargos 775:780 analyte cargos 767:780 analyte cargos over droplets 767:794 The magnetic tweezer technology was employed to manipulate (capture and release) coated magnetic beads used as analyte cargos over droplets. 35934380 7 34 theme microfluidic 1110:1121 arg1 version 1123:1129 a novel microfluidic version 1102:1129 a novel microfluidic version 1102:1129 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 8 35 link N-linked 1211:1218 arg1 oligosaccharides 1220:1235 N-linked oligosaccharides 1211:1235 N-linked oligosaccharides from Human Immuglobulin G 1211:1261 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 9 36 theme glycan 1606:1611 arg1 profile 1624:1630 glycan separation profile 1606:1630 glycan separation profile obtained by capillary electrophoresis 1606:1668 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 9 37 theme profile 1624:1630 arg1 degradation 1591:1601 degradation 1591:1601 degradation of glycan separation profile obtained by capillary electrophoresis 1591:1668 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 1 38 theme sample 226:231 arg1 treatment 233:241 multistep glycoprotein sample treatment 203:241 multistep glycoprotein sample treatment 203:241 We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. 35934380 2 39 gly glycoprotein 312:323 arg1 glycoprotein 312:323 a given glycoprotein to profile its N-glycans 304:348 a given glycoprotein to profile its N-glycans 304:348 Several operations are required for the sample treatment of a given glycoprotein to profile its N-glycans. 35934380 3 40 gly glycoproteins 421:433 arg1 glycoproteins 421:433 glycoproteins 421:433 glycoproteins 421:433 In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. 35934380 3 41 from glycoproteins 421:433 arg1 analysis 394:401 the analysis 390:401 the analysis of N-glycans from glycoproteins 390:433 In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. 35934380 3 41 from glycoproteins 421:433 arg1 N-glycans 406:414 N-glycans 406:414 N-glycans from glycoproteins 406:433 In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. 35934380 1 42 attach present 118:124 arg2 We 115:116 We 115:116 We 115:116 We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. 35934380 1 42 attach present 118:124 arg1 study 134:138 this study 129:138 this study 129:138 We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. 35934380 10 43 theme N-linked 1757:1764 arg1 glycans 1766:1772 N-linked glycans 1757:1772 N-linked glycans 1757:1772 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 7 44 from feasible 1037:1044 arg1 mode 1071:1074 batchwise mode 1061:1074 batchwise mode 1061:1074 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 4 45 theme previous 577:584 arg1 setups 594:599 previous droplet setups 577:599 previous droplet setups 577:599 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 7 46 theme batchwise 1061:1069 arg1 mode 1071:1074 batchwise mode 1061:1074 batchwise mode 1061:1074 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 2 47 theme sample 284:289 arg1 treatment 291:299 the sample treatment 280:299 the sample treatment of a given glycoprotein to profile its N-glycans 280:348 Several operations are required for the sample treatment of a given glycoprotein to profile its N-glycans. 35934380 9 48 theme conventional 1444:1455 arg1 protocol 1467:1474 the conventional batchwise protocol 1440:1474 the conventional batchwise protocol 1440:1474 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 6 49 theme microreactors 856:868 arg1 role 839:842 the role 835:842 the role of confined microreactors 835:868 Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. 35934380 1 50 gly glycoprotein 213:224 arg1 glycoprotein 213:224 multistep glycoprotein sample treatment 203:241 multistep glycoprotein sample treatment 203:241 We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. 35934380 2 51 theme given 306:310 arg1 glycoprotein 312:323 a given glycoprotein to profile its N-glycans 304:348 a given glycoprotein to profile its N-glycans 304:348 Several operations are required for the sample treatment of a given glycoprotein to profile its N-glycans. 35934380 10 52 theme diagnostic 1812:1821 arg1 screening 1823:1831 diagnostic screening 1812:1831 diagnostic screening of congenital disorders of glycosylation 1812:1872 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 9 53 theme 2-fold 1538:1543 arg1 improvement 1545:1555 2-fold improvement 1538:1555 2-fold improvement of glycan labeling yield 1538:1580 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 8 54 theme Human 1242:1246 arg1 G 1261:1261 Human Immuglobulin G 1242:1261 Human Immuglobulin G 1242:1261 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 2 55 theme Several 244:250 arg1 operations 252:261 Several operations 244:261 Several operations 244:261 Several operations are required for the sample treatment of a given glycoprotein to profile its N-glycans. 35934380 9 56 theme less 1490:1493 arg1 consumption 1503:1513 10-fold less reagent consumption 1482:1513 10-fold less reagent consumption 1482:1513 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 4 57 theme droplet 627:633 arg1 sensing 635:641 droplet sensing 627:641 droplet sensing 627:641 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 4 57 theme droplet 627:633 arg1 features 548:555 several features 540:555 several features that are not met in previous droplet setups 540:599 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 5 58 theme capture 716:722 arg1 beads 753:757 (capture and release) coated magnetic beads 715:757 (capture and release) coated magnetic beads used as analyte cargos over droplets 715:794 The magnetic tweezer technology was employed to manipulate (capture and release) coated magnetic beads used as analyte cargos over droplets. 35934380 5 59 theme magnetic 660:667 arg1 technology 677:686 The magnetic tweezer technology 656:686 The magnetic tweezer technology 656:686 The magnetic tweezer technology was employed to manipulate (capture and release) coated magnetic beads used as analyte cargos over droplets. 35934380 10 60 theme congenital 1836:1845 arg1 disorders 1847:1855 congenital disorders 1836:1855 congenital disorders of glycosylation 1836:1872 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 7 61 theme sample 997:1002 arg1 feasible 1037:1044 feasible 1037:1044 feasible 1037:1044 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 7 61 theme sample 997:1002 arg1 protocol 1014:1021 A complex sample treatment protocol 987:1021 A complex sample treatment protocol that has been feasible so far only in batchwise mode 987:1074 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 7 62 theme treatment 1004:1012 arg1 feasible 1037:1044 feasible 1037:1044 feasible 1037:1044 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 7 62 theme treatment 1004:1012 arg1 protocol 1014:1021 A complex sample treatment protocol 987:1021 A complex sample treatment protocol that has been feasible so far only in batchwise mode 987:1074 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 6 63 with mixing 957:962 arg1 solvents 977:984 organic solvents 969:984 organic solvents 969:984 Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. 35934380 5 64 theme coated 737:742 arg1 beads 753:757 (capture and release) coated magnetic beads 715:757 (capture and release) coated magnetic beads used as analyte cargos over droplets 715:794 The magnetic tweezer technology was employed to manipulate (capture and release) coated magnetic beads used as analyte cargos over droplets. 35934380 8 65 from G 1261:1261 arg1 oligosaccharides 1220:1235 N-linked oligosaccharides 1211:1235 N-linked oligosaccharides from Human Immuglobulin G 1211:1261 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 8 66 theme labeled 1293:1299 arg1 glycans 1301:1307 the labeled glycans 1289:1307 the labeled glycans 1289:1307 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 8 67 with electrophoresis 1322:1336 arg1 detection 1369:1377 laser induced fluorescent detection 1343:1377 laser induced fluorescent detection 1343:1377 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 0 68 theme disorders 87:95 arg1 screening 63:71 diagnostic screening 52:71 diagnostic screening of congenital disorders of glycosylation 52:112 Lab-in-droplet: From glycan sample treatment toward diagnostic screening of congenital disorders of glycosylation. 35934380 3 69 from analysis 394:401 arg1 glycoproteins 421:433 glycoproteins 421:433 glycoproteins 421:433 In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. 35934380 1 70 theme microfluidic 146:157 arg1 platform 167:174 a new microfluidic droplet platform 140:174 a new microfluidic droplet platform 140:174 We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. 35934380 0 71 theme glycosylation 100:112 arg1 disorders 87:95 congenital disorders 76:95 congenital disorders of glycosylation 76:112 Lab-in-droplet: From glycan sample treatment toward diagnostic screening of congenital disorders of glycosylation. 35934380 5 72 theme release 728:734 arg1 beads 753:757 (capture and release) coated magnetic beads 715:757 (capture and release) coated magnetic beads used as analyte cargos over droplets 715:794 The magnetic tweezer technology was employed to manipulate (capture and release) coated magnetic beads used as analyte cargos over droplets. 35934380 9 73 theme glycan 1560:1565 arg1 yield 1576:1580 glycan labeling yield 1560:1580 glycan labeling yield 1560:1580 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 0 74 from treatment 35:43 arg1 Lab-in-droplet 0:13 Lab-in-droplet: 0:14 Lab-in-droplet: From glycan sample treatment toward diagnostic screening of congenital disorders of glycosylation. 0:113 Lab-in-droplet: From glycan sample treatment toward diagnostic screening of congenital disorders of glycosylation. 35934380 9 75 theme yield 1576:1580 arg1 consumption 1503:1513 10-fold less reagent consumption 1482:1513 10-fold less reagent consumption 1482:1513 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 9 75 theme yield 1576:1580 arg1 improvement 1545:1555 2-fold improvement 1538:1555 2-fold improvement of glycan labeling yield 1538:1580 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 9 75 theme yield 1576:1580 arg1 time 1528:1531 3-fold less time 1516:1531 3-fold less time 1516:1531 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 8 76 theme fluorescent 1357:1367 arg1 detection 1369:1377 laser induced fluorescent detection 1343:1377 laser induced fluorescent detection 1343:1377 With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. 35934380 0 77 theme glycan 21:26 arg1 treatment 35:43 glycan sample treatment 21:43 glycan sample treatment 21:43 Lab-in-droplet: From glycan sample treatment toward diagnostic screening of congenital disorders of glycosylation. 35934380 3 78 theme preparation 368:378 arg1 steps 380:384 all preparation steps 364:384 all preparation steps for the analysis of N-glycans from glycoproteins 364:433 In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. 35934380 10 79 attach released 1774:1781 arg1 sera 1794:1797 human sera 1788:1797 human sera 1788:1797 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 10 79 attach released 1774:1781 arg2 glycans 1766:1772 N-linked glycans 1757:1772 N-linked glycans 1757:1772 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 10 80 theme droplet 1703:1709 arg1 protocol 1711:1718 the developed droplet protocol 1689:1718 the developed droplet protocol 1689:1718 The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation. 35934380 7 81 theme novel 1104:1108 arg1 version 1123:1129 a novel microfluidic version 1102:1129 a novel microfluidic version 1102:1129 A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. 35934380 1 82 theme multistep 203:211 arg1 treatment 233:241 multistep glycoprotein sample treatment 203:241 multistep glycoprotein sample treatment 203:241 We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. 35934380 3 83 theme N-glycans 406:414 arg1 analysis 394:401 the analysis 390:401 the analysis of N-glycans from glycoproteins 390:433 In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. 35934380 0 84 theme diagnostic 52:61 arg1 screening 63:71 diagnostic screening 52:71 diagnostic screening of congenital disorders of glycosylation 52:112 Lab-in-droplet: From glycan sample treatment toward diagnostic screening of congenital disorders of glycosylation. 35934380 9 85 theme separation 1613:1622 arg1 profile 1624:1630 glycan separation profile 1606:1630 glycan separation profile obtained by capillary electrophoresis 1606:1668 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 4 86 theme several 540:546 arg1 heating 647:653 heating 647:653 heating 647:653 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 4 86 theme several 540:546 arg1 automation 615:624 full automation 610:624 full automation 610:624 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 4 86 theme several 540:546 arg1 sensing 635:641 droplet sensing 627:641 droplet sensing 627:641 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 4 86 theme several 540:546 arg1 met 570:572 met 570:572 met in previous droplet setups 570:599 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 4 86 theme several 540:546 arg1 features 548:555 several features 540:555 several features that are not met in previous droplet setups 540:599 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 3 87 theme cross 488:492 arg1 contamination 494:506 cross contamination 488:506 cross contamination 488:506 In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. 35934380 1 88 theme glycoprotein 213:224 arg1 treatment 233:241 multistep glycoprotein sample treatment 203:241 multistep glycoprotein sample treatment 203:241 We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. 35934380 9 89 theme capillary 1644:1652 arg1 electrophoresis 1654:1668 capillary electrophoresis 1644:1668 capillary electrophoresis 1644:1668 We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. 35934380 4 90 theme full 610:613 arg1 automation 615:624 full automation 610:624 full automation 610:624 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 35934380 4 90 theme full 610:613 arg1 features 548:555 several features 540:555 several features that are not met in previous droplet setups 540:599 This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. 36912991 4 0 theme cucumber 760:767 arg1 WD1 781:783 the North China-type cucumber inbred line WD1 739:783 the North China-type cucumber inbred line WD1 739:783 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 3 1 theme regulatory 490:499 arg1 mechanisms 501:510 The regulatory mechanisms 486:510 The regulatory mechanisms underlying plant organ size and shape 486:548 The regulatory mechanisms underlying plant organ size and shape are important and fundamental biological questions. 36912991 3 1 theme regulatory 490:499 arg1 questions 591:599 important and fundamental biological questions 554:599 important and fundamental biological questions 554:599 The regulatory mechanisms underlying plant organ size and shape are important and fundamental biological questions. 36912991 7 2 theme single 1071:1076 arg1 G 1078:1078 a single G 1069:1078 a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 1069:1149 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 10 3 theme cell 1647:1650 arg1 networks 1682:1689 cell proliferation-associated gene networks 1647:1689 cell proliferation-associated gene networks 1647:1689 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 5 4 theme sf4 854:856 arg1 phenotype 841:849 the short fruit length phenotype 818:849 the short fruit length phenotype of sf4 818:856 Genetic analysis indicated that the short fruit length phenotype of sf4 was controlled by a recessive nuclear gene. 36912991 3 5 theme fundamental 568:578 arg1 mechanisms 501:510 The regulatory mechanisms 486:510 The regulatory mechanisms underlying plant organ size and shape 486:548 The regulatory mechanisms underlying plant organ size and shape are important and fundamental biological questions. 36912991 3 5 theme fundamental 568:578 arg1 questions 591:599 important and fundamental biological questions 554:599 important and fundamental biological questions 554:599 The regulatory mechanisms underlying plant organ size and shape are important and fundamental biological questions. 36912991 1 6 theme short 188:192 arg1 phenotype 207:215 The short fruit length phenotype 184:215 The short fruit length phenotype in sf4 184:222 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 6 7 theme genomic 942:948 arg1 region 950:955 a 116.7-kb genomic region 931:955 a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1 931:1015 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 7 8 from deletion 1217:1224 arg1 exon 1229:1232 exon 22 1229:1235 exon 22 1229:1235 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 4 9 theme length 631:636 arg1 mutant 638:643 a short-fruit length mutant 617:643 a short-fruit length mutant 617:643 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 4 9 theme length 631:636 arg1 sf4 646:648 sf4 646:648 sf4 646:648 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 3 10 theme important 554:562 arg1 mechanisms 501:510 The regulatory mechanisms 486:510 The regulatory mechanisms underlying plant organ size and shape 486:548 The regulatory mechanisms underlying plant organ size and shape are important and fundamental biological questions. 36912991 3 10 theme important 554:562 arg1 questions 591:599 important and fundamental biological questions 554:599 important and fundamental biological questions 554:599 The regulatory mechanisms underlying plant organ size and shape are important and fundamental biological questions. 36912991 5 11 theme fruit 828:832 arg1 phenotype 841:849 the short fruit length phenotype 818:849 the short fruit length phenotype of sf4 818:856 Genetic analysis indicated that the short fruit length phenotype of sf4 was controlled by a recessive nuclear gene. 36912991 1 12 from SNP 239:241 arg1 Csa1G665390 246:256 Csa1G665390 246:256 Csa1G665390 246:256 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 1 13 from phenotype 207:215 arg1 sf4 220:222 sf4 220:222 sf4 220:222 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 11 14 from mechanisms 1866:1875 arg1 cucumber 1880:1887 cucumber 1880:1887 cucumber 1880:1887 Identification of CsSF4 will contribute to elucidating the function of OGT in cell proliferation and to understanding fruit elongation mechanisms in cucumber. 36912991 10 15 theme genes 1527:1531 arg1 regulation 1583:1592 cell cycle regulation 1572:1592 cell cycle regulation 1572:1592 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 10 15 theme genes 1527:1531 arg1 replication 1599:1609 DNA replication 1595:1609 DNA replication 1595:1609 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 10 15 theme genes 1527:1531 arg1 expression 1508:1517 expression 1508:1517 expression of many genes involved in hormone response pathways 1508:1569 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 10 15 theme genes 1527:1531 arg1 division 1621:1628 cell division 1616:1628 cell division 1616:1628 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 11 16 theme CsSF4 1749:1753 arg1 Identification 1731:1744 Identification 1731:1744 Identification of CsSF4 1731:1753 Identification of CsSF4 will contribute to elucidating the function of OGT in cell proliferation and to understanding fruit elongation mechanisms in cucumber. 36912991 7 17 theme Genomic 1018:1024 arg1 analysis 1045:1052 Genomic and cDNA sequences analysis 1018:1052 Genomic and cDNA sequences analysis 1018:1052 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 4 18 theme mutagenesis 703:713 arg1 population 715:724 an ethyl methanesulfonate (EMS) mutagenesis population 671:724 an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1 671:783 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 9 19 theme male 1410:1413 arg1 flowers 1415:1421 male flowers 1410:1421 male flowers 1410:1421 CsSF4 was highly expressed in the leaves and male flowers of wild-type cucumbers. 36912991 0 20 dep cucumber 153:160 arg1 Cucumis 163:169 Cucumis 163:169 Cucumis 163:169 Mapping and identification of CsSF4, a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.). 36912991 4 21 theme methanesulfonate 680:695 arg1 population 715:724 an ethyl methanesulfonate (EMS) mutagenesis population 671:724 an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1 671:783 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 0 22 theme UDP-N-acetyl 55:66 arg1 N-acetylglucosaminyltransferase 88:118 a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase 53:118 a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.) 53:181 Mapping and identification of CsSF4, a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.). 36912991 5 23 theme nuclear 888:894 arg1 gene 896:899 a recessive nuclear gene 876:899 a recessive nuclear gene 876:899 Genetic analysis indicated that the short fruit length phenotype of sf4 was controlled by a recessive nuclear gene. 36912991 6 24 theme SNP 969:971 arg1 markers 973:979 the SNP markers GCSNP75 and GCSNP82 965:999 the SNP markers GCSNP75 and GCSNP82 on chromosome 1 965:1015 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 6 24 theme SNP 969:971 arg1 GCSNP82 993:999 GCSNP82 993:999 GCSNP82 993:999 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 6 24 theme SNP 969:971 arg1 GCSNP75 981:987 GCSNP75 981:987 GCSNP75 981:987 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 7 25 from nucleotide 1108:1117 arg1 transition 1085:1094 A transition 1083:1094 A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 1083:1149 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 4 26 theme China-type 749:758 arg1 WD1 781:783 the North China-type cucumber inbred line WD1 739:783 the North China-type cucumber inbred line WD1 739:783 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 10 27 theme gene 1677:1680 arg1 networks 1682:1689 cell proliferation-associated gene networks 1647:1689 cell proliferation-associated gene networks 1647:1689 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 0 28 dep Cucumis 163:169 arg1 L 179:179 sativus L 171:179 Cucumis sativus L. 163:180 Mapping and identification of CsSF4, a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.). 36912991 4 29 theme inbred 769:774 arg1 WD1 781:783 the North China-type cucumber inbred line WD1 739:783 the North China-type cucumber inbred line WD1 739:783 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 10 30 theme cell 1572:1575 arg1 regulation 1583:1592 cell cycle regulation 1572:1592 cell cycle regulation 1572:1592 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 2 31 theme growth 425:430 arg1 rate 432:435 its fast growth rate 416:435 its fast growth rate 416:435 Cucumber fruit is an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations. 36912991 6 32 from markers 973:979 arg1 chromosome 1004:1013 chromosome 1 1004:1015 chromosome 1 1004:1015 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 2 33 theme excellent 360:368 arg1 resource 370:377 an excellent resource 357:377 an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations 357:483 Cucumber fruit is an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations. 36912991 2 33 theme excellent 360:368 arg1 fruit 348:352 Cucumber fruit 339:352 Cucumber fruit 339:352 Cucumber fruit is an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations. 36912991 7 34 dep GT-AA 1189:1193 arg1 GT-AG 1180:1184 GT-AG 1180:1184 GT-AG 1180:1184 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 6 35 located located 920:926 arg2 locus 910:914 The SF4 locus 902:914 The SF4 locus 902:914 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 6 35 located located 920:926 arg2 located 920:926 located 920:926 located 920:926 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 6 35 located located 920:926 arg1 region 950:955 a 116.7-kb genomic region 931:955 a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1 931:1015 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 10 36 theme DNA 1595:1597 arg1 replication 1599:1609 DNA replication 1595:1609 DNA replication 1595:1609 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 7 37 theme Csa1G665390 1122:1132 arg1 intron 1134:1139 Csa1G665390 intron 21 1122:1142 Csa1G665390 intron 21 1122:1142 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 10 38 theme proliferation-associated 1652:1675 arg1 networks 1682:1689 cell proliferation-associated gene networks 1647:1689 cell proliferation-associated gene networks 1647:1689 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 2 39 theme abundant 451:458 arg1 variations 474:483 naturally abundant morphological variations 441:483 naturally abundant morphological variations 441:483 Cucumber fruit is an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations. 36912991 6 40 from region 950:955 arg1 located 920:926 located 920:926 located 920:926 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 6 40 from region 950:955 arg1 locus 910:914 The SF4 locus 902:914 The SF4 locus 902:914 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 11 41 theme elongation 1855:1864 arg1 mechanisms 1866:1875 fruit elongation mechanisms 1849:1875 fruit elongation mechanisms in cucumber 1849:1887 Identification of CsSF4 will contribute to elucidating the function of OGT in cell proliferation and to understanding fruit elongation mechanisms in cucumber. 36912991 8 42 theme O-linked 1308:1315 arg1 N-acetylglucosamine 1317:1335 O-linked N-acetylglucosamine 1308:1335 an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 1305:1362 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 8 42 theme O-linked 1308:1315 arg1 GlcNAc 1338:1343 GlcNAc 1338:1343 GlcNAc 1338:1343 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 2 43 theme fruit 392:396 arg1 morphology 398:407 fruit morphology 392:407 fruit morphology 392:407 Cucumber fruit is an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations. 36912991 0 44 theme CsSF4 30:34 arg1 identification 12:25 identification 12:25 identification 12:25 Mapping and identification of CsSF4, a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.). 36912991 0 44 theme CsSF4 30:34 arg1 Mapping 0:6 Mapping 0:6 Mapping 0:6 Mapping and identification of CsSF4, a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.). 36912991 0 44 theme CsSF4 30:34 arg1 gene 39:42 a gene 37:42 a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.) 37:181 Mapping and identification of CsSF4, a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.). 36912991 1 45 theme O-linked 276:283 arg1 N-acetylglucosamine 285:303 O-linked N-acetylglucosamine 276:303 an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber 273:336 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 1 45 theme O-linked 276:283 arg1 GlcNAc 306:311 GlcNAc 306:311 GlcNAc 306:311 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 10 46 theme cell 1616:1619 arg1 division 1621:1628 cell division 1616:1628 cell division 1616:1628 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 5 47 theme Genetic 786:792 arg1 analysis 794:801 Genetic analysis 786:801 Genetic analysis 786:801 Genetic analysis indicated that the short fruit length phenotype of sf4 was controlled by a recessive nuclear gene. 36912991 7 48 from transition 1085:1094 arg1 sf4 1147:1149 sf4 1147:1149 sf4 1147:1149 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 11 49 theme OGT 1802:1804 arg1 function 1790:1797 the function 1786:1797 the function of OGT in cell proliferation 1786:1826 Identification of CsSF4 will contribute to elucidating the function of OGT in cell proliferation and to understanding fruit elongation mechanisms in cucumber. 36912991 10 50 from alterations 1493:1503 arg1 regulation 1583:1592 cell cycle regulation 1572:1592 cell cycle regulation 1572:1592 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 10 50 from alterations 1493:1503 arg1 replication 1599:1609 DNA replication 1595:1609 DNA replication 1595:1609 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 10 50 from alterations 1493:1503 arg1 expression 1508:1517 expression 1508:1517 expression of many genes involved in hormone response pathways 1508:1569 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 10 50 from alterations 1493:1503 arg1 division 1621:1628 cell division 1616:1628 cell division 1616:1628 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 11 51 theme cell 1809:1812 arg1 proliferation 1814:1826 cell proliferation 1809:1826 cell proliferation 1809:1826 Identification of CsSF4 will contribute to elucidating the function of OGT in cell proliferation and to understanding fruit elongation mechanisms in cucumber. 36912991 6 52 theme SF4 906:908 arg1 located 920:926 located 920:926 located 920:926 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 6 52 theme SF4 906:908 arg1 locus 910:914 The SF4 locus 902:914 The SF4 locus 902:914 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 0 53 from elongation 139:148 arg1 cucumber 153:160 cucumber 153:160 cucumber (Cucumis sativus L.) 153:181 Mapping and identification of CsSF4, a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.). 36912991 10 54 theme Transcriptome 1447:1459 arg1 analysis 1461:1468 Transcriptome analysis 1447:1468 Transcriptome analysis 1447:1468 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 7 55 theme splice 1163:1168 arg1 site 1170:1173 the splice site 1159:1173 the splice site 1159:1173 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 2 56 theme Cucumber 339:346 arg1 resource 370:377 an excellent resource 357:377 an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations 357:483 Cucumber fruit is an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations. 36912991 2 56 theme Cucumber 339:346 arg1 fruit 348:352 Cucumber fruit 339:352 Cucumber fruit 339:352 Cucumber fruit is an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations. 36912991 9 57 theme wild-type 1426:1434 arg1 cucumbers 1436:1444 wild-type cucumbers 1426:1444 wild-type cucumbers 1426:1444 CsSF4 was highly expressed in the leaves and male flowers of wild-type cucumbers. 36912991 3 58 theme organ 529:533 arg1 size 535:538 plant organ size 523:538 plant organ size 523:538 The regulatory mechanisms underlying plant organ size and shape are important and fundamental biological questions. 36912991 1 59 from transferase 314:324 arg1 cucumber 329:336 cucumber 329:336 cucumber 329:336 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 10 60 theme many 1522:1525 arg1 genes 1527:1531 many genes 1522:1531 many genes involved in hormone response pathways 1522:1569 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 7 61 theme sequences 1035:1043 arg1 analysis 1045:1052 Genomic and cDNA sequences analysis 1018:1052 Genomic and cDNA sequences analysis 1018:1052 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 10 62 theme fruit 1700:1704 arg1 development 1706:1716 fruit development 1700:1716 fruit development 1700:1716 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 5 63 theme short 822:826 arg1 phenotype 841:849 the short fruit length phenotype 818:849 the short fruit length phenotype of sf4 818:856 Genetic analysis indicated that the short fruit length phenotype of sf4 was controlled by a recessive nuclear gene. 36912991 6 64 theme 116.7-kb 933:940 arg1 region 950:955 a 116.7-kb genomic region 931:955 a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1 931:1015 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 4 65 theme short-fruit 619:629 arg1 mutant 638:643 a short-fruit length mutant 617:643 a short-fruit length mutant 617:643 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 4 65 theme short-fruit 619:629 arg1 sf4 646:648 sf4 646:648 sf4 646:648 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 10 66 theme hormone 1545:1551 arg1 pathways 1562:1569 hormone response pathways 1545:1569 hormone response pathways 1545:1569 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 5 67 theme length 834:839 arg1 phenotype 841:849 the short fruit length phenotype 818:849 the short fruit length phenotype of sf4 818:856 Genetic analysis indicated that the short fruit length phenotype of sf4 was controlled by a recessive nuclear gene. 36912991 4 68 attach derived 726:732 arg2 population 715:724 an ethyl methanesulfonate (EMS) mutagenesis population 671:724 an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1 671:783 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 4 68 attach derived 726:732 arg1 WD1 781:783 the North China-type cucumber inbred line WD1 739:783 the North China-type cucumber inbred line WD1 739:783 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 0 69 theme sativus 171:177 arg1 L 179:179 sativus L 171:179 Cucumis sativus L. 163:180 Mapping and identification of CsSF4, a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.). 36912991 3 70 theme biological 580:589 arg1 mechanisms 501:510 The regulatory mechanisms 486:510 The regulatory mechanisms underlying plant organ size and shape 486:548 The regulatory mechanisms underlying plant organ size and shape are important and fundamental biological questions. 36912991 3 70 theme biological 580:589 arg1 questions 591:599 important and fundamental biological questions 554:599 important and fundamental biological questions 554:599 The regulatory mechanisms underlying plant organ size and shape are important and fundamental biological questions. 36912991 1 71 theme fruit 194:198 arg1 phenotype 207:215 The short fruit length phenotype 184:215 The short fruit length phenotype in sf4 184:222 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 8 72 link O-linked 1308:1315 arg1 N-acetylglucosamine 1317:1335 O-linked N-acetylglucosamine 1308:1335 an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 1305:1362 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 8 72 link O-linked 1308:1315 arg1 GlcNAc 1338:1343 GlcNAc 1338:1343 GlcNAc 1338:1343 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 0 73 theme glucosamine-peptide 68:86 arg1 N-acetylglucosaminyltransferase 88:118 a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase 53:118 a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.) 53:181 Mapping and identification of CsSF4, a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.). 36912991 6 74 from located 920:926 arg1 region 950:955 a 116.7-kb genomic region 931:955 a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1 931:1015 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 5 75 theme recessive 878:886 arg1 gene 896:899 a recessive nuclear gene 876:899 a recessive nuclear gene 876:899 Genetic analysis indicated that the short fruit length phenotype of sf4 was controlled by a recessive nuclear gene. 36912991 2 76 theme morphological 460:472 arg1 variations 474:483 naturally abundant morphological variations 441:483 naturally abundant morphological variations 441:483 Cucumber fruit is an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations. 36912991 6 77 dep markers 973:979 arg1 markers 973:979 the SNP markers GCSNP75 and GCSNP82 965:999 the SNP markers GCSNP75 and GCSNP82 on chromosome 1 965:1015 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 6 77 dep markers 973:979 arg1 GCSNP82 993:999 GCSNP82 993:999 GCSNP82 993:999 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 6 77 dep markers 973:979 arg1 GCSNP75 981:987 GCSNP75 981:987 GCSNP75 981:987 The SF4 locus was located in a 116.7-kb genomic region between the SNP markers GCSNP75 and GCSNP82 on chromosome 1. 36912991 4 78 theme ethyl 674:678 arg1 EMS 698:700 EMS 698:700 EMS 698:700 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 4 78 theme ethyl 674:678 arg1 methanesulfonate 680:695 ethyl methanesulfonate 674:695 an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1 671:783 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 0 79 theme fruit 133:137 arg1 elongation 139:148 fruit elongation 133:148 fruit elongation in cucumber (Cucumis sativus L.) 133:181 Mapping and identification of CsSF4, a gene encoding a UDP-N-acetyl glucosamine-peptide N-acetylglucosaminyltransferase required for fruit elongation in cucumber (Cucumis sativus L.). 36912991 1 80 theme length 200:205 arg1 phenotype 207:215 The short fruit length phenotype 184:215 The short fruit length phenotype in sf4 184:222 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 9 81 dep leaves 1399:1404 arg1 the 1395:1397 the 1395:1397 the 1395:1397 CsSF4 was highly expressed in the leaves and male flowers of wild-type cucumbers. 36912991 11 82 theme fruit 1849:1853 arg1 mechanisms 1866:1875 fruit elongation mechanisms 1849:1875 fruit elongation mechanisms in cucumber 1849:1887 Identification of CsSF4 will contribute to elucidating the function of OGT in cell proliferation and to understanding fruit elongation mechanisms in cucumber. 36912991 7 83 theme intron 1134:1139 arg1 nucleotide 1108:1117 the last nucleotide 1099:1117 the last nucleotide of Csa1G665390 intron 21 1099:1142 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 2 84 theme fast 420:423 arg1 rate 432:435 its fast growth rate 416:435 its fast growth rate 416:435 Cucumber fruit is an excellent resource for studying fruit morphology due to its fast growth rate and naturally abundant morphological variations. 36912991 11 85 from function 1790:1797 arg1 proliferation 1814:1826 cell proliferation 1809:1826 cell proliferation 1809:1826 Identification of CsSF4 will contribute to elucidating the function of OGT in cell proliferation and to understanding fruit elongation mechanisms in cucumber. 36912991 10 86 theme response 1553:1560 arg1 pathways 1562:1569 hormone response pathways 1545:1569 hormone response pathways 1545:1569 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 10 87 contain had 1489:1491 arg2 alterations 1493:1503 alterations 1493:1503 alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division 1493:1628 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 10 87 contain had 1489:1491 arg1 sf4 1485:1487 sf4 1485:1487 sf4 1485:1487 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 7 88 theme last 1103:1106 arg1 nucleotide 1108:1117 the last nucleotide 1099:1117 the last nucleotide of Csa1G665390 intron 21 1099:1142 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 10 89 theme cycle 1577:1581 arg1 regulation 1583:1592 cell cycle regulation 1572:1592 cell cycle regulation 1572:1592 Transcriptome analysis indicated that sf4 had alterations in expression of many genes involved in hormone response pathways, cell cycle regulation, DNA replication, and cell division, suggesting that cell proliferation-associated gene networks regulate fruit development in cucumber. 36912991 1 90 theme N-acetylglucosamine 285:303 arg1 SNP 239:241 a SNP 237:241 a SNP 237:241 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 1 90 theme N-acetylglucosamine 285:303 arg1 transferase 314:324 an O-linked N-acetylglucosamine (GlcNAc) transferase 273:324 an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber 273:336 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 7 91 theme 42-bp 1211:1215 arg1 deletion 1217:1224 a 42-bp deletion 1209:1224 a 42-bp deletion in exon 22 1209:1235 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 7 92 theme cDNA 1030:1033 arg1 sequences 1035:1043 cDNA sequences 1030:1043 cDNA sequences 1030:1043 Genomic and cDNA sequences analysis indicated that a single G to A transition at the last nucleotide of Csa1G665390 intron 21 in sf4 changed the splice site from GT-AG to GT-AA, resulting in a 42-bp deletion in exon 22. 36912991 8 93 theme N-acetylglucosamine 1317:1335 arg1 OGT 1359:1361 OGT 1359:1361 OGT 1359:1361 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 8 93 theme N-acetylglucosamine 1317:1335 arg1 gene 1280:1283 a candidate gene 1268:1283 a candidate gene 1268:1283 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 8 93 theme N-acetylglucosamine 1317:1335 arg1 transferase 1346:1356 an O-linked N-acetylglucosamine (GlcNAc) transferase 1305:1356 an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 1305:1362 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 1 94 link O-linked 276:283 arg1 N-acetylglucosamine 285:303 O-linked N-acetylglucosamine 276:303 an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber 273:336 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 1 94 link O-linked 276:283 arg1 GlcNAc 306:311 GlcNAc 306:311 GlcNAc 306:311 The short fruit length phenotype in sf4 is caused by a SNP in Csa1G665390, which encodes an O-linked N-acetylglucosamine (GlcNAc) transferase in cucumber. 36912991 8 95 theme candidate 1270:1278 arg1 CsSF4 1286:1290 CsSF4 1286:1290 CsSF4 1286:1290 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 8 95 theme candidate 1270:1278 arg1 gene 1280:1283 a candidate gene 1268:1283 a candidate gene 1268:1283 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 8 95 theme candidate 1270:1278 arg1 transferase 1346:1356 an O-linked N-acetylglucosamine (GlcNAc) transferase 1305:1356 an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 1305:1362 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 8 95 theme candidate 1270:1278 arg1 Csa1G665390 1238:1248 Csa1G665390 1238:1248 Csa1G665390 1238:1248 Csa1G665390 is presumed to be a candidate gene, CsSF4 that encodes an O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). 36912991 4 96 theme line 776:779 arg1 WD1 781:783 the North China-type cucumber inbred line WD1 739:783 the North China-type cucumber inbred line WD1 739:783 In this study, a short-fruit length mutant, sf4, was identified from an ethyl methanesulfonate (EMS) mutagenesis population derived from the North China-type cucumber inbred line WD1. 36912991 3 97 theme plant 523:527 arg1 size 535:538 plant organ size 523:538 plant organ size 523:538 The regulatory mechanisms underlying plant organ size and shape are important and fundamental biological questions. 36090029 5 0 from analysis 791:798 arg1 microbiota 807:816 gut microbiota 803:816 gut microbiota 803:816 Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. 36090029 4 1 theme IgAN 586:589 arg1 patients 591:598 20 IgAN patients 583:598 20 IgAN patients (IgAN group) 583:611 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 4 1 theme IgAN 586:589 arg1 group 606:610 IgAN group 601:610 IgAN group 601:610 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 14 2 theme Gd-IgA1-associated 2342:2359 arg1 α-galactosidase 2361:2375 that Gd-IgA1-associated α-galactosidase 2337:2375 that Gd-IgA1-associated α-galactosidase 2337:2375 Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients. 36090029 9 3 theme Enterotype 1439:1448 arg1 I 1450:1450 Enterotype I 1439:1450 Enterotype I characterized by Bacteroides 1439:1479 Enterotype I characterized by Bacteroides was closely related to the IgAN patients. 36090029 12 4 theme biochemical 2097:2107 arg1 features 2109:2116 clinical and biochemical features 2084:2116 clinical and biochemical features 2084:2116 These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. 36090029 2 5 theme IgA1 291:294 arg1 expression 257:266 higher expression 250:266 higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity 250:349 Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. 36090029 7 6 theme quantitative 1110:1121 arg1 calculation 1123:1133 the quantitative calculation 1106:1133 the quantitative calculation of enzymes encoded by microbiome 1106:1166 Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. 36090029 8 7 theme plebeius 1278:1285 arg1 levels 1312:1317 Bacteroides plebeius and Bacteroides vulgatus levels 1266:1317 Bacteroides plebeius and Bacteroides vulgatus levels 1266:1317 Results: Bacteroides plebeius and Bacteroides vulgatus levels were higher, while Prevotella copri and Alistipes putredinis levels were lower in the IgAN group compared to HCs group. 36090029 5 8 theme microbiota 857:866 arg1 composition 868:878 the overall microbiota composition 845:878 the overall microbiota composition 845:878 Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. 36090029 12 9 theme clinical 2084:2091 arg1 features 2109:2116 clinical and biochemical features 2084:2116 clinical and biochemical features 2084:2116 These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. 36090029 4 10 theme healthy 620:626 arg1 controls 628:635 20 healthy controls 617:635 20 healthy controls (HCs group) 617:647 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 4 10 theme healthy 620:626 arg1 group 642:646 HCs group 638:646 HCs group 638:646 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 11 11 theme blood 1870:1874 arg1 cells 1876:1880 red blood cells 1866:1880 red blood cells 1866:1880 Spearman's correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. 36090029 7 12 theme microbial 1080:1088 arg1 communities 1090:1100 microbial communities 1080:1100 microbial communities 1080:1100 Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. 36090029 13 13 theme acids 2242:2246 arg1 biosynthesis 2220:2231 the biosynthesis 2216:2231 the biosynthesis of amino acids and glycans 2216:2258 In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. 36090029 4 14 with sequencing 526:535 arg1 Illumina 542:549 Illumina 542:549 Illumina 542:549 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 15 15 theme IgAN 2815:2818 arg1 pathogenesis 2799:2810 the pathogenesis 2795:2810 the pathogenesis of IgAN 2795:2818 Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN. 36090029 12 16 theme IgAN 2046:2049 arg1 patients 2051:2058 IgAN patients 2046:2058 IgAN patients 2046:2058 These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. 36090029 13 17 theme glycans 2252:2258 arg1 biosynthesis 2220:2231 the biosynthesis 2216:2231 the biosynthesis of amino acids and glycans 2216:2258 In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. 36090029 15 18 theme intestinal 2699:2708 arg1 microbiota 2710:2719 abnormal intestinal microbiota 2690:2719 abnormal intestinal microbiota 2690:2719 Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN. 36090029 1 19 theme glomerulonephritis 196:213 arg1 Background 134:143 Background 134:143 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 134:222 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 1 19 theme glomerulonephritis 196:213 arg1 type 188:191 the most common type 172:191 the most common type of glomerulonephritis in Asia 172:221 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 1 19 theme glomerulonephritis 196:213 arg1 nephropathy 150:160 IgA nephropathy 146:160 IgA nephropathy (IgAN) 146:167 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 15 20 theme abnormal 2690:2697 arg1 microbiota 2710:2719 abnormal intestinal microbiota 2690:2719 abnormal intestinal microbiota 2690:2719 Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN. 36090029 2 21 theme higher 250:255 arg1 expression 257:266 higher expression 250:266 higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity 250:349 Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. 36090029 14 22 dep analysis 2316:2323 arg1 highlighted 2325:2335 highlighted 2325:2335 highlighted that Gd-IgA1-associated α-galactosidase 2325:2375 Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients. 36090029 14 22 dep analysis 2316:2323 arg1 secreted 2410:2417 secreted 2410:2417 α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii 2381:2443 Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients. 36090029 8 23 theme copri 1349:1353 arg1 levels 1380:1385 Prevotella copri and Alistipes putredinis levels 1338:1385 Prevotella copri and Alistipes putredinis levels 1338:1385 Results: Bacteroides plebeius and Bacteroides vulgatus levels were higher, while Prevotella copri and Alistipes putredinis levels were lower in the IgAN group compared to HCs group. 36090029 13 24 theme metabolic 2186:2194 arg1 pathways 2196:2203 microbiota-related metabolic pathways 2167:2203 microbiota-related metabolic pathways 2167:2203 In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. 36090029 13 24 theme metabolic 2186:2194 arg1 biosynthesis 2220:2231 the biosynthesis 2216:2231 the biosynthesis of amino acids and glycans 2216:2258 In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. 36090029 15 25 theme Gd-IgA1 2757:2763 arg1 production 2743:2752 the production 2739:2752 the production of Gd-IgA1 2739:2763 Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN. 36090029 5 26 theme representative 885:898 arg1 enterotypes 900:910 the representative enterotypes 881:910 the representative enterotypes 881:910 Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. 36090029 4 27 theme shotgun 506:512 arg1 sequencing 526:535 shotgun metagenomic sequencing 506:535 shotgun metagenomic sequencing with Illumina 506:549 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 4 28 theme Second 710:715 arg1 College 726:732 the Second Clinical College 706:732 the Second Clinical College of Guangzhou University of Chinese Medicine 706:776 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 11 29 theme direct 1842:1847 arg1 association 1849:1859 a direct association 1840:1859 a direct association with red blood cells 1840:1880 Spearman's correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. 36090029 0 30 theme key 105:107 arg1 role 109:112 a key role 103:112 a key role 103:112 Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy. 36090029 13 31 theme pathway 2140:2146 arg1 analysis 2148:2155 MetaCyc pathway analysis 2132:2155 MetaCyc pathway analysis 2132:2155 In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. 36090029 6 32 theme clinical 983:990 arg1 indicators 992:1001 clinical indicators 983:1001 clinical indicators 983:1001 Correlations between gut microbiota and clinical indicators were assessed by Spearman's analysis. 36090029 4 33 theme University 747:756 arg1 College 726:732 the Second Clinical College 706:732 the Second Clinical College of Guangzhou University of Chinese Medicine 706:776 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 0 34 theme Metagenomics-based 0:17 arg1 analysis 30:37 Metagenomics-based systematic analysis 0:37 Metagenomics-based systematic analysis 0:37 Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy. 36090029 3 35 theme study 374:378 arg1 objective 356:364 The objective 352:364 The objective of this study 352:378 The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN. 36090029 4 36 theme fecal 554:558 arg1 samples 560:566 fecal samples 554:566 fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine 554:776 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 4 37 theme Clinical 717:724 arg1 College 726:732 the Second Clinical College 706:732 the Second Clinical College of Guangzhou University of Chinese Medicine 706:776 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 14 38 theme Flavonifractor 2422:2435 arg1 plautii 2437:2443 Flavonifractor plautii 2422:2443 Flavonifractor plautii 2422:2443 Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients. 36090029 5 39 theme gut 803:805 arg1 microbiota 807:816 gut microbiota 803:816 gut microbiota 803:816 Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. 36090029 3 40 theme gut 412:414 arg1 microbiota 416:425 specific gut microbiota 403:425 specific gut microbiota 403:425 The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN. 36090029 11 41 theme urine 1775:1779 arg1 ratio 1800:1804 urine protein-creatinine ratio 1775:1804 urine protein-creatinine ratio 1775:1804 Spearman's correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. 36090029 0 42 theme microbiota 56:65 arg1 enzymes 86:92 gut microbiota Gd-IgA1-associated enzymes 52:92 gut microbiota Gd-IgA1-associated enzymes 52:92 Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy. 36090029 15 43 theme Gd-IgA1 2641:2647 arg1 production 2627:2636 the production 2623:2636 the production of Gd-IgA1 2623:2647 Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN. 36090029 4 44 theme Chinese 761:767 arg1 Medicine 769:776 Chinese Medicine 761:776 Chinese Medicine 761:776 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 13 45 theme MetaCyc 2132:2138 arg1 analysis 2148:2155 MetaCyc pathway analysis 2132:2155 MetaCyc pathway analysis 2132:2155 In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. 36090029 2 46 theme mucosal 334:340 arg1 immunity 342:349 dysregulated intestinal mucosal immunity 310:349 dysregulated intestinal mucosal immunity 310:349 Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. 36090029 13 47 theme IgAN 2286:2289 arg1 group 2291:2295 the IgAN group 2282:2295 the IgAN group 2282:2295 In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. 36090029 4 48 theme IgAN 601:604 arg1 patients 591:598 20 IgAN patients 583:598 20 IgAN patients (IgAN group) 583:611 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 4 48 theme IgAN 601:604 arg1 group 606:610 IgAN group 601:610 IgAN group 601:610 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 7 49 theme enzymes 1138:1144 arg1 prediction 1066:1075 the functional prediction 1051:1075 the functional prediction of microbial communities 1051:1100 Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. 36090029 7 49 theme enzymes 1138:1144 arg1 calculation 1123:1133 the quantitative calculation 1106:1133 the quantitative calculation of enzymes encoded by microbiome 1106:1166 Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. 36090029 4 50 contain carried 494:500 arg2 sequencing 526:535 shotgun metagenomic sequencing 506:535 shotgun metagenomic sequencing with Illumina 506:549 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 4 50 contain carried 494:500 arg1 study 488:492 This study 483:492 This study 483:492 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 4 50 contain carried 494:500 arg3 samples 560:566 fecal samples 554:566 fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine 554:776 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 10 51 theme characteristic 1607:1620 arg1 bacteria 1622:1629 characteristic bacteria 1607:1629 characteristic bacteria enriched in IgAN patients 1607:1655 Moreover, Bacteroides fragilis, Flavonifractor plautii and Ruminococcus gnavus were characteristic bacteria enriched in IgAN patients. 36090029 5 52 theme Differences 779:789 arg1 analysis 791:798 Differences analysis 779:798 Differences analysis in gut microbiota 779:816 Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. 36090029 2 53 theme galactose-deficient 271:289 arg1 IgA1 291:294 galactose-deficient IgA1 271:294 galactose-deficient IgA1 (Gd-IgA1) 271:304 Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. 36090029 2 53 theme galactose-deficient 271:289 arg1 Gd-IgA1 297:303 Gd-IgA1 297:303 Gd-IgA1 297:303 Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. 36090029 4 54 theme HCs 638:640 arg1 controls 628:635 20 healthy controls 617:635 20 healthy controls (HCs group) 617:647 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 4 54 theme HCs 638:640 arg1 group 642:646 HCs group 638:646 HCs group 638:646 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 14 55 theme Microbial 2298:2306 arg1 enzymes 2308:2314 Microbial enzymes 2298:2314 Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii 2298:2443 Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients. 36090029 7 56 theme communities 1090:1100 arg1 prediction 1066:1075 the functional prediction 1051:1075 the functional prediction of microbial communities 1051:1100 Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. 36090029 7 56 theme communities 1090:1100 arg1 calculation 1123:1133 the quantitative calculation 1106:1133 the quantitative calculation of enzymes encoded by microbiome 1106:1166 Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. 36090029 2 57 theme dysregulated 310:321 arg1 immunity 342:349 dysregulated intestinal mucosal immunity 310:349 dysregulated intestinal mucosal immunity 310:349 Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. 36090029 5 58 theme overall 849:855 arg1 composition 868:878 the overall microbiota composition 845:878 the overall microbiota composition 845:878 Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. 36090029 10 59 theme IgAN 1643:1646 arg1 patients 1648:1655 IgAN patients 1643:1655 IgAN patients 1643:1655 Moreover, Bacteroides fragilis, Flavonifractor plautii and Ruminococcus gnavus were characteristic bacteria enriched in IgAN patients. 36090029 1 60 theme common 181:186 arg1 Background 134:143 Background 134:143 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 134:222 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 1 60 theme common 181:186 arg1 type 188:191 the most common type 172:191 the most common type of glomerulonephritis in Asia 172:221 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 1 60 theme common 181:186 arg1 nephropathy 150:160 IgA nephropathy 146:160 IgA nephropathy (IgAN) 146:167 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 6 61 theme gut 964:966 arg1 microbiota 968:977 gut microbiota 964:977 gut microbiota 964:977 Correlations between gut microbiota and clinical indicators were assessed by Spearman's analysis. 36090029 7 62 theme functional 1055:1064 arg1 prediction 1066:1075 the functional prediction 1051:1075 the functional prediction of microbial communities 1051:1100 Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. 36090029 8 63 theme vulgatus 1303:1310 arg1 levels 1312:1317 Bacteroides plebeius and Bacteroides vulgatus levels 1266:1317 Bacteroides plebeius and Bacteroides vulgatus levels 1266:1317 Results: Bacteroides plebeius and Bacteroides vulgatus levels were higher, while Prevotella copri and Alistipes putredinis levels were lower in the IgAN group compared to HCs group. 36090029 15 64 theme Flavonifractor 2580:2593 arg1 plautii 2595:2601 Flavonifractor plautii 2580:2601 Flavonifractor plautii 2580:2601 Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN. 36090029 11 65 with association 1849:1859 arg1 cells 1876:1880 red blood cells 1866:1880 red blood cells 1866:1880 Spearman's correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. 36090029 1 66 from type 188:191 arg1 Asia 218:221 Asia 218:221 Asia 218:221 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 13 67 theme amino 2236:2240 arg1 acids 2242:2246 amino acids 2236:2246 amino acids 2236:2246 In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. 36090029 1 68 theme IgA 146:148 arg1 type 188:191 the most common type 172:191 the most common type of glomerulonephritis in Asia 172:221 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 1 68 theme IgA 146:148 arg1 nephropathy 150:160 IgA nephropathy 146:160 IgA nephropathy (IgAN) 146:167 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 1 68 theme IgA 146:148 arg1 Background 134:143 Background 134:143 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 134:222 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 1 68 theme IgA 146:148 arg1 IgAN 163:166 IgAN 163:166 IgAN 163:166 Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. 36090029 14 69 dep enzymes 2308:2314 arg1 analysis 2316:2323 analysis 2316:2323 Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii 2298:2443 Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients. 36090029 10 70 dep Flavonifractor 1555:1568 arg1 plautii 1570:1576 Flavonifractor plautii 1555:1576 Flavonifractor plautii 1555:1576 Moreover, Bacteroides fragilis, Flavonifractor plautii and Ruminococcus gnavus were characteristic bacteria enriched in IgAN patients. 36090029 12 71 theme intestinal 2008:2017 arg1 dysbacteriosis 2019:2032 intestinal dysbacteriosis 2008:2032 intestinal dysbacteriosis 2008:2032 These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. 36090029 4 72 theme metagenomic 514:524 arg1 sequencing 526:535 shotgun metagenomic sequencing 506:535 shotgun metagenomic sequencing with Illumina 506:549 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 11 73 theme red 1866:1868 arg1 cells 1876:1880 red blood cells 1866:1880 red blood cells 1866:1880 Spearman's correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. 36090029 7 74 theme bioBakery 1217:1225 arg1 platform 1233:1240 the bioBakery three platform 1213:1240 the bioBakery three platform 1213:1240 Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. 36090029 4 75 dep January 673:679 arg1 to 686:687 to 686:687 to 686:687 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 4 75 dep January 673:679 arg1 December 689:696 December 689:696 December 689:696 Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. 36090029 8 76 theme putredinis 1369:1378 arg1 levels 1380:1385 Prevotella copri and Alistipes putredinis levels 1338:1385 Prevotella copri and Alistipes putredinis levels 1338:1385 Results: Bacteroides plebeius and Bacteroides vulgatus levels were higher, while Prevotella copri and Alistipes putredinis levels were lower in the IgAN group compared to HCs group. 36090029 14 77 theme IgAN 2462:2465 arg1 patients 2467:2474 IgAN patients 2462:2474 IgAN patients 2462:2474 Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients. 36090029 0 78 theme IgA 117:119 arg1 nephropathy 121:131 IgA nephropathy 117:131 IgA nephropathy 117:131 Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy. 36090029 0 79 theme systematic 19:28 arg1 analysis 30:37 Metagenomics-based systematic analysis 0:37 Metagenomics-based systematic analysis 0:37 Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy. 36090029 13 80 theme microbiota-related 2167:2184 arg1 pathways 2196:2203 microbiota-related metabolic pathways 2167:2203 microbiota-related metabolic pathways 2167:2203 In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. 36090029 13 80 theme microbiota-related 2167:2184 arg1 biosynthesis 2220:2231 the biosynthesis 2216:2231 the biosynthesis of amino acids and glycans 2216:2258 In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. 36090029 5 81 theme microbiota 921:930 arg1 abundance 932:940 the microbiota abundance 917:940 the microbiota abundance 917:940 Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. 36090029 3 82 theme associated 431:440 arg1 enzymes 442:448 associated enzymes 431:448 associated enzymes 431:448 The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN. 36090029 8 83 theme IgAN 1405:1408 arg1 group 1410:1414 the IgAN group 1401:1414 the IgAN group 1401:1414 Results: Bacteroides plebeius and Bacteroides vulgatus levels were higher, while Prevotella copri and Alistipes putredinis levels were lower in the IgAN group compared to HCs group. 36090029 0 84 theme gut 52:54 arg1 enzymes 86:92 gut microbiota Gd-IgA1-associated enzymes 52:92 gut microbiota Gd-IgA1-associated enzymes 52:92 Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy. 36090029 0 85 theme Gd-IgA1-associated 67:84 arg1 enzymes 86:92 gut microbiota Gd-IgA1-associated enzymes 52:92 gut microbiota Gd-IgA1-associated enzymes 52:92 Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy. 36090029 3 86 theme specific 403:410 arg1 microbiota 416:425 specific gut microbiota 403:425 specific gut microbiota 403:425 The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN. 36090029 8 87 theme HCs 1428:1430 arg1 group 1432:1436 HCs group 1428:1436 HCs group 1428:1436 Results: Bacteroides plebeius and Bacteroides vulgatus levels were higher, while Prevotella copri and Alistipes putredinis levels were lower in the IgAN group compared to HCs group. 36090029 2 88 theme immunity 342:349 arg1 expression 257:266 higher expression 250:266 higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity 250:349 Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. 36090029 11 89 theme protein-creatinine 1781:1798 arg1 ratio 1800:1804 urine protein-creatinine ratio 1775:1804 urine protein-creatinine ratio 1775:1804 Spearman's correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. 36090029 11 90 theme correlation 1669:1679 arg1 analysis 1681:1688 Spearman's correlation analysis 1658:1688 Spearman's correlation analysis 1658:1688 Spearman's correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. 36090029 2 91 theme intestinal 323:332 arg1 immunity 342:349 dysregulated intestinal mucosal immunity 310:349 dysregulated intestinal mucosal immunity 310:349 Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. 36090029 9 92 theme IgAN 1508:1511 arg1 patients 1513:1520 the IgAN patients 1504:1520 the IgAN patients 1504:1520 Enterotype I characterized by Bacteroides was closely related to the IgAN patients. 36090029 7 93 theme MetaCyc 1193:1199 arg1 pathway 1201:1207 the MetaCyc pathway 1189:1207 the MetaCyc pathway 1189:1207 Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. 36090029 15 94 theme important 2777:2785 arg1 role 2787:2790 an important role 2774:2790 an important role 2774:2790 Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN. 37043835 4 0 theme activity 909:916 arg1 different 937:945 different 937:945 different 937:945 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 4 0 theme activity 909:916 arg1 contents 866:873 the contents 862:873 the contents of some nutrients and antioxidant activity 862:916 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 6 1 theme correct 1330:1336 arg1 rate 1353:1356 the correct discrimination rate 1326:1356 the correct discrimination rate of the testing sample set obtained with the established model 1326:1418 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 5 2 theme fingerprint 1060:1070 arg1 bands 1072:1076 The characteristic fingerprint bands 1041:1076 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT 1041:1170 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT were screened out. 37043835 3 3 dep Fourier 530:536 arg1 transform 538:546 transform 538:546 transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) 538:732 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 4 theme RRT 816:818 arg1 origin 806:811 the geographical origin 789:811 the geographical origin of RRT 789:818 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 8 5 theme RRT 1664:1666 arg1 origins 1653:1659 the geographical origins 1636:1659 the geographical origins of RRT 1636:1666 The characteristic fingerprint bands of RRT obtained with FT-IR could be used to identify the geographical origins of RRT more quickly and accurately. 37043835 4 6 theme antioxidant 897:907 arg1 activity 909:916 antioxidant activity 897:916 antioxidant activity 897:916 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 0 7 from analysis 8:15 arg1 regions 92:98 three regions 86:98 three regions 86:98 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 6 8 theme different 1304:1312 arg1 regions 1314:1320 different regions 1304:1320 different regions 1304:1320 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 0 9 dep transform 117:125 arg1 infrared 127:134 infrared 127:134 transform infrared spectroscopy 117:147 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 3 10 theme geographical 793:804 arg1 origin 806:811 the geographical origin 789:811 the geographical origin of RRT 789:818 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 11 theme discriminant 757:768 arg1 models 770:775 discriminant models 757:775 discriminant models to identify the geographical origin of RRT 757:818 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 0 12 dep Fourier 109:115 arg1 transform 117:125 transform 117:125 transform infrared spectroscopy 117:147 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 4 13 theme FT-IR 990:994 arg1 spectra 996:1002 their FT-IR spectra 984:1002 their FT-IR spectra 984:1002 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 1 14 theme functional 246:255 arg1 foods 257:261 functional foods 246:261 functional foods 246:261 The study aimed to provide new information of Rosa roxburghii Tratt (RRT) for the production of functional foods and distinguish the geographical origins of RRT. 37043835 3 15 theme discriminant 644:655 arg1 SLDA 667:670 SLDA 667:670 SLDA 667:670 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 15 theme discriminant 644:655 arg1 analysis 657:664 stepwise linear discriminant analysis 628:664 stepwise linear discriminant analysis (SLDA) 628:671 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 6 16 theme discriminant 1208:1219 arg1 model 1221:1225 a discriminant model 1206:1225 a discriminant model 1206:1225 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 1 17 theme foods 257:261 arg1 production 232:241 the production 228:241 the production of functional foods 228:261 The study aimed to provide new information of Rosa roxburghii Tratt (RRT) for the production of functional foods and distinguish the geographical origins of RRT. 37043835 5 18 theme related 1129:1135 arg1 FT-IR 1081:1085 FT-IR 1081:1085 FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT 1081:1170 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT were screened out. 37043835 5 18 theme related 1129:1135 arg1 1520-900 cm-1 1106:1118 1679-1618 cm-1and 1520-900 cm-1 1088:1118 1679-1618 cm-1and 1520-900 cm-1 1088:1118 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT were screened out. 37043835 3 19 used used 739:742 arg2 results 519:525 The results 515:525 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) 515:732 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 8 20 theme geographical 1640:1651 arg1 origins 1653:1659 the geographical origins 1636:1659 the geographical origins of RRT 1636:1666 The characteristic fingerprint bands of RRT obtained with FT-IR could be used to identify the geographical origins of RRT more quickly and accurately. 37043835 8 21 used used 1619:1622 arg2 bands 1577:1581 The characteristic fingerprint bands 1546:1581 The characteristic fingerprint bands of RRT obtained with FT-IR 1546:1608 The characteristic fingerprint bands of RRT obtained with FT-IR could be used to identify the geographical origins of RRT more quickly and accurately. 37043835 5 22 theme characteristic 1045:1058 arg1 bands 1072:1076 The characteristic fingerprint bands 1041:1076 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT 1041:1170 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT were screened out. 37043835 6 23 theme sample 1373:1378 arg1 set 1380:1382 the testing sample set 1361:1382 the testing sample set obtained with the established model 1361:1418 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 2 24 theme total 411:415 arg1 flavonoids 417:426 total flavonoids 411:426 total flavonoids 411:426 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities were analyzed by one-way ANOVA. 37043835 1 25 theme new 177:179 arg1 information 181:191 new information 177:191 new information of Rosa roxburghii Tratt (RRT) 177:222 The study aimed to provide new information of Rosa roxburghii Tratt (RRT) for the production of functional foods and distinguish the geographical origins of RRT. 37043835 7 26 theme antioxidant 1517:1527 arg1 activity 1529:1536 antioxidant activity 1517:1536 antioxidant activity 1517:1536 Geographical factors caused the obvious differences in nutritional components and antioxidant activity in RRT. 37043835 0 27 from origin 34:39 arg1 regions 92:98 three regions 86:98 three regions 86:98 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 8 28 theme fingerprint 1565:1575 arg1 bands 1577:1581 The characteristic fingerprint bands 1546:1581 The characteristic fingerprint bands of RRT obtained with FT-IR 1546:1608 The characteristic fingerprint bands of RRT obtained with FT-IR could be used to identify the geographical origins of RRT more quickly and accurately. 37043835 2 29 theme antioxidant 460:470 arg1 activities 472:481 their antioxidant activities 454:481 their antioxidant activities 454:481 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities were analyzed by one-way ANOVA. 37043835 3 30 theme Fourier 530:536 arg1 results 519:525 The results 515:525 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) 515:732 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 0 31 theme Quality 0:6 arg1 analysis 8:15 Quality analysis 0:15 Quality analysis 0:15 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 4 32 from regions 972:978 arg1 different 937:945 different 937:945 different 937:945 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 4 32 from regions 972:978 arg1 contents 866:873 the contents 862:873 the contents of some nutrients and antioxidant activity 862:916 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 2 33 from regions 357:363 arg1 components 328:337 The nutritional components 312:337 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities 312:481 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities were analyzed by one-way ANOVA. 37043835 2 33 from regions 357:363 arg1 China 368:372 China 368:372 China 368:372 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities were analyzed by one-way ANOVA. 37043835 7 34 theme obvious 1467:1473 arg1 differences 1475:1485 the obvious differences 1463:1485 the obvious differences in nutritional components and antioxidant activity in RRT 1463:1543 Geographical factors caused the obvious differences in nutritional components and antioxidant activity in RRT. 37043835 0 35 theme geographical 21:32 arg1 origin 34:39 geographical origin 21:39 geographical origin 21:39 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 4 36 theme ANOVA 844:848 arg1 results 825:831 The results 821:831 The results of one-way ANOVA 821:848 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 6 37 from regions 1314:1320 arg1 identification 1277:1290 identification 1277:1290 identification 1277:1290 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 6 37 from regions 1314:1320 arg1 classification 1258:1271 classification 1258:1271 classification 1258:1271 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 1 38 theme Rosa 196:199 arg1 RRT 219:221 RRT 219:221 RRT 219:221 The study aimed to provide new information of Rosa roxburghii Tratt (RRT) for the production of functional foods and distinguish the geographical origins of RRT. 37043835 1 38 theme Rosa 196:199 arg1 Tratt 212:216 Rosa roxburghii Tratt 196:216 Rosa roxburghii Tratt (RRT) 196:222 The study aimed to provide new information of Rosa roxburghii Tratt (RRT) for the production of functional foods and distinguish the geographical origins of RRT. 37043835 4 39 theme different 962:970 arg1 regions 972:978 different regions 962:978 different regions 962:978 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 4 40 theme one-way 836:842 arg1 ANOVA 844:848 one-way ANOVA 836:848 one-way ANOVA 836:848 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 6 41 theme testing 1365:1371 arg1 set 1380:1382 the testing sample set 1361:1382 the testing sample set obtained with the established model 1361:1418 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 2 42 theme RRT 342:344 arg1 components 328:337 The nutritional components 312:337 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities 312:481 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities were analyzed by one-way ANOVA. 37043835 1 43 theme roxburghii 201:210 arg1 RRT 219:221 RRT 219:221 RRT 219:221 The study aimed to provide new information of Rosa roxburghii Tratt (RRT) for the production of functional foods and distinguish the geographical origins of RRT. 37043835 1 43 theme roxburghii 201:210 arg1 Tratt 212:216 Rosa roxburghii Tratt 196:216 Rosa roxburghii Tratt (RRT) 196:222 The study aimed to provide new information of Rosa roxburghii Tratt (RRT) for the production of functional foods and distinguish the geographical origins of RRT. 37043835 5 44 theme geographical 1144:1155 arg1 origins 1157:1163 the geographical origins 1140:1163 the geographical origins of RRT 1140:1170 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT were screened out. 37043835 1 45 theme geographical 283:294 arg1 origins 296:302 the geographical origins 279:302 the geographical origins of RRT 279:309 The study aimed to provide new information of Rosa roxburghii Tratt (RRT) for the production of functional foods and distinguish the geographical origins of RRT. 37043835 6 46 theme established 1402:1412 arg1 model 1414:1418 the established model 1398:1418 the established model 1398:1418 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 1 47 theme Tratt 212:216 arg1 information 181:191 new information 177:191 new information of Rosa roxburghii Tratt (RRT) 177:222 The study aimed to provide new information of Rosa roxburghii Tratt (RRT) for the production of functional foods and distinguish the geographical origins of RRT. 37043835 3 48 theme k-nearest 674:682 arg1 k-NN 694:697 k-NN 694:697 k-NN 694:697 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 48 theme k-nearest 674:682 arg1 neighbor 684:691 k-nearest neighbor 674:691 k-nearest neighbor (k-NN) 674:698 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 2 49 theme vitamin 383:389 arg1 C 391:391 vitamin C 383:391 vitamin C 383:391 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities were analyzed by one-way ANOVA. 37043835 2 50 theme total 433:437 arg1 phenolics 439:447 total phenolics 433:447 total phenolics 433:447 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities were analyzed by one-way ANOVA. 37043835 3 51 theme vector 713:718 arg1 SVM 729:731 SVM 729:731 SVM 729:731 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 51 theme vector 713:718 arg1 machine 720:726 support vector machine 705:726 support vector machine (SVM) 705:732 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 2 52 theme one-way 500:506 arg1 ANOVA 508:512 one-way ANOVA 500:512 one-way ANOVA 500:512 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities were analyzed by one-way ANOVA. 37043835 3 53 theme component 602:610 arg1 PCA 622:624 PCA 622:624 PCA 622:624 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 53 theme component 602:610 arg1 analysis 612:619 principal component analysis 592:619 principal component analysis (PCA) 592:625 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 6 54 dep classification 1258:1271 arg1 the 1254:1256 the 1254:1256 the 1254:1256 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 8 55 theme characteristic 1550:1563 arg1 bands 1577:1581 The characteristic fingerprint bands 1546:1581 The characteristic fingerprint bands of RRT obtained with FT-IR 1546:1608 The characteristic fingerprint bands of RRT obtained with FT-IR could be used to identify the geographical origins of RRT more quickly and accurately. 37043835 5 56 theme 1679-1618 cm-1and 1088:1104 arg1 FT-IR 1081:1085 FT-IR 1081:1085 FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT 1081:1170 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT were screened out. 37043835 5 56 theme 1679-1618 cm-1and 1088:1104 arg1 1520-900 cm-1 1106:1118 1679-1618 cm-1and 1520-900 cm-1 1088:1118 1679-1618 cm-1and 1520-900 cm-1 1088:1118 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT were screened out. 37043835 6 57 theme discrimination 1338:1351 arg1 rate 1353:1356 the correct discrimination rate 1326:1356 the correct discrimination rate of the testing sample set obtained with the established model 1326:1418 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 3 58 theme infrared 548:555 arg1 FT-IR 571:575 FT-IR 571:575 FT-IR 571:575 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 58 theme infrared 548:555 arg1 spectroscopy 557:568 infrared spectroscopy 548:568 infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) 548:732 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 5 59 theme FT-IR 1081:1085 arg1 bands 1072:1076 The characteristic fingerprint bands 1041:1076 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT 1041:1170 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT were screened out. 37043835 1 60 theme RRT 307:309 arg1 origins 296:302 the geographical origins 279:302 the geographical origins of RRT 279:309 The study aimed to provide new information of Rosa roxburghii Tratt (RRT) for the production of functional foods and distinguish the geographical origins of RRT. 37043835 6 61 theme RRT 1295:1297 arg1 identification 1277:1290 identification 1277:1290 identification 1277:1290 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 6 61 theme RRT 1295:1297 arg1 classification 1258:1271 classification 1258:1271 classification 1258:1271 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 3 62 theme stepwise 628:635 arg1 SLDA 667:670 SLDA 667:670 SLDA 667:670 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 62 theme stepwise 628:635 arg1 analysis 657:664 stepwise linear discriminant analysis 628:664 stepwise linear discriminant analysis (SLDA) 628:671 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 7 63 from differences 1475:1485 arg1 RRT 1541:1543 RRT 1541:1543 RRT 1541:1543 Geographical factors caused the obvious differences in nutritional components and antioxidant activity in RRT. 37043835 7 63 from differences 1475:1485 arg1 components 1502:1511 nutritional components 1490:1511 nutritional components 1490:1511 Geographical factors caused the obvious differences in nutritional components and antioxidant activity in RRT. 37043835 7 63 from differences 1475:1485 arg1 activity 1529:1536 antioxidant activity 1517:1536 antioxidant activity 1517:1536 Geographical factors caused the obvious differences in nutritional components and antioxidant activity in RRT. 37043835 3 64 theme support 705:711 arg1 SVM 729:731 SVM 729:731 SVM 729:731 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 64 theme support 705:711 arg1 machine 720:726 support vector machine 705:726 support vector machine (SVM) 705:732 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 65 theme linear 637:642 arg1 SLDA 667:670 SLDA 667:670 SLDA 667:670 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 65 theme linear 637:642 arg1 analysis 657:664 stepwise linear discriminant analysis 628:664 stepwise linear discriminant analysis (SLDA) 628:671 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 5 66 theme RRT 1168:1170 arg1 origins 1157:1163 the geographical origins 1140:1163 the geographical origins of RRT 1140:1170 The characteristic fingerprint bands of FT-IR (1679-1618 cm-1and 1520-900 cm-1) closely related to the geographical origins of RRT were screened out. 37043835 2 67 theme nutritional 316:326 arg1 components 328:337 The nutritional components 312:337 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities 312:481 The nutritional components of RRT from three regions in China, such as vitamin C, polysaccharides, total flavonoids, and total phenolics, and their antioxidant activities were analyzed by one-way ANOVA. 37043835 7 68 theme nutritional 1490:1500 arg1 components 1502:1511 nutritional components 1490:1511 nutritional components 1490:1511 Geographical factors caused the obvious differences in nutritional components and antioxidant activity in RRT. 37043835 3 69 theme principal 592:600 arg1 PCA 622:624 PCA 622:624 PCA 622:624 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 3 69 theme principal 592:600 arg1 analysis 612:619 principal component analysis 592:619 principal component analysis (PCA) 592:625 The results of Fourier transform infrared spectroscopy (FT-IR) combined with principal component analysis (PCA), stepwise linear discriminant analysis (SLDA), k-nearest neighbor (k-NN), and support vector machine (SVM) were used to establish discriminant models to identify the geographical origin of RRT. 37043835 0 70 theme Tratt 75:79 arg1 analysis 8:15 Quality analysis 0:15 Quality analysis 0:15 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 0 70 theme Tratt 75:79 arg1 origin 34:39 geographical origin 21:39 geographical origin 21:39 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 0 71 from regions 92:98 arg1 analysis 8:15 Quality analysis 0:15 Quality analysis 0:15 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 0 71 from regions 92:98 arg1 origin 34:39 geographical origin 21:39 geographical origin 21:39 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 0 72 dep analysis 8:15 arg1 identification 41:54 identification 41:54 identification 41:54 Quality analysis and geographical origin identification of Rosa roxburghii Tratt from three regions based on Fourier transform infrared spectroscopy. 37043835 4 73 theme significant 1016:1026 arg1 differences 1028:1038 significant differences 1016:1038 significant differences 1016:1038 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 4 74 theme nutrients 883:891 arg1 different 937:945 different 937:945 different 937:945 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 4 74 theme nutrients 883:891 arg1 contents 866:873 the contents 862:873 the contents of some nutrients and antioxidant activity 862:916 The results of one-way ANOVA showed that the contents of some nutrients and antioxidant activity were significantly different among RRT from different regions and their FT-IR spectra also showed significant differences. 37043835 7 75 theme Geographical 1435:1446 arg1 factors 1448:1454 Geographical factors 1435:1454 Geographical factors 1435:1454 Geographical factors caused the obvious differences in nutritional components and antioxidant activity in RRT. 37043835 6 76 theme set 1380:1382 arg1 rate 1353:1356 the correct discrimination rate 1326:1356 the correct discrimination rate of the testing sample set obtained with the established model 1326:1418 Based on SLDA, a discriminant model was established to realize the classification and identification of RRT from different regions and the correct discrimination rate of the testing sample set obtained with the established model reached 100 %. 37043835 8 77 theme RRT 1586:1588 arg1 bands 1577:1581 The characteristic fingerprint bands 1546:1581 The characteristic fingerprint bands of RRT obtained with FT-IR 1546:1608 The characteristic fingerprint bands of RRT obtained with FT-IR could be used to identify the geographical origins of RRT more quickly and accurately. 37238813 4 0 theme lees 671:674 arg1 aging 676:680 lees aging 671:680 lees aging 671:680 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 1 1 theme yeast 149:153 arg1 strains 155:161 only a few yeast strains 138:161 only a few yeast strains 138:161 In sparkling winemaking, only a few yeast strains are regularly used for the secondary in-bottle alcoholic fermentation (SiBAF). 37238813 7 2 theme balance 1328:1334 arg1 terms 1300:1304 terms 1300:1304 terms of aroma and bouquet, balance, finish, overall liking and preference 1300:1373 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 2 3 theme hybrids 343:349 arg1 breeds 308:313 new breeds 304:313 new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas 304:415 Recently, advances in yeast development programs have yielded new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas. 37238813 8 4 theme wines 1566:1570 arg1 elaboration 1541:1551 the elaboration 1537:1551 the elaboration of sparkling wines 1537:1570 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 0 5 theme Wines 106:110 arg1 Fermentation 72:83 Secondary In-Bottle Alcoholic Fermentation 42:83 Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines 42:110 Effect of Interspecific Yeast Hybrids for Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines. 37238813 5 6 theme macromolecular 962:975 arg1 contents 977:984 their macromolecular contents 956:984 their macromolecular contents 956:984 Chemically, the yeast strains did not result in significant differences in the main wine parameters, while some differences in their macromolecular contents and sensory characteristics were noticeable. 37238813 3 7 theme commercial 544:553 arg1 wines 568:572 three commercial English base wines 538:572 three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids 538:649 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 5 8 theme main 908:911 arg1 parameters 918:927 the main wine parameters 904:927 the main wine parameters 904:927 Chemically, the yeast strains did not result in significant differences in the main wine parameters, while some differences in their macromolecular contents and sensory characteristics were noticeable. 37238813 2 9 theme development 270:280 arg1 programs 282:289 yeast development programs 264:289 yeast development programs 264:289 Recently, advances in yeast development programs have yielded new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas. 37238813 7 10 theme preference 1364:1373 arg1 terms 1300:1304 terms 1300:1304 terms of aroma and bouquet, balance, finish, overall liking and preference 1300:1373 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 4 11 theme aging 676:680 arg1 months 661:666 12 months 658:666 12 months of lees aging 658:680 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 2 12 theme yeast 337:341 arg1 hybrids 343:349 interspecific wine yeast hybrids 318:349 interspecific wine yeast hybrids 318:349 Recently, advances in yeast development programs have yielded new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas. 37238813 6 13 theme yeast 1228:1232 arg1 strains 1234:1240 the yeast strains 1224:1240 the yeast strains 1224:1240 The foamability was mostly unaffected by the strain used; however, some effect on the foam stability was noticeable, likely due to the differences in polysaccharides released into the wines by the yeast strains. 37238813 2 14 theme yeast 264:268 arg1 programs 282:289 yeast development programs 264:289 yeast development programs 264:289 Recently, advances in yeast development programs have yielded new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas. 37238813 8 15 theme aroma 1638:1642 arg1 attributes 1644:1653 aroma attributes 1638:1653 aroma attributes 1638:1653 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 3 16 theme use 474:476 arg1 impacts 459:465 the chemical and sensorial impacts 432:465 the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF 432:517 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 2 17 theme novel 392:396 arg1 flavors 398:404 novel flavors 392:404 novel flavors 392:404 Recently, advances in yeast development programs have yielded new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas. 37238813 8 18 theme yeast 1507:1511 arg1 hybrids 1513:1519 Novel interspecific yeast hybrids 1487:1519 Novel interspecific yeast hybrids 1487:1519 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 3 19 theme English 555:561 arg1 wines 568:572 three commercial English base wines 538:572 three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids 538:649 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 8 20 theme similar 1655:1661 arg1 characteristics 1610:1624 chemical characteristics 1601:1624 chemical characteristics 1601:1624 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 5 21 theme yeast 845:849 arg1 strains 851:857 the yeast strains 841:857 the yeast strains 841:857 Chemically, the yeast strains did not result in significant differences in the main wine parameters, while some differences in their macromolecular contents and sensory characteristics were noticeable. 37238813 7 22 from differences 1418:1428 arg1 strain 1464:1469 the strain 1460:1469 the base wines rather than the strain used for SiBAF 1433:1484 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 7 22 from differences 1418:1428 arg1 wines 1442:1446 the base wines 1433:1446 the base wines rather than the strain used for SiBAF 1433:1484 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 8 23 theme interspecific 1493:1505 arg1 hybrids 1513:1519 Novel interspecific yeast hybrids 1487:1519 Novel interspecific yeast hybrids 1487:1519 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 2 24 theme new 304:306 arg1 breeds 308:313 new breeds 304:313 new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas 304:415 Recently, advances in yeast development programs have yielded new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas. 37238813 0 25 theme Yeast 24:28 arg1 Hybrids 30:36 Interspecific Yeast Hybrids 10:36 Interspecific Yeast Hybrids 10:36 Effect of Interspecific Yeast Hybrids for Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines. 37238813 8 26 theme Novel 1487:1491 arg1 hybrids 1513:1519 Novel interspecific yeast hybrids 1487:1519 Novel interspecific yeast hybrids 1487:1519 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 5 27 from differences 889:899 arg1 parameters 918:927 the main wine parameters 904:927 the main wine parameters 904:927 Chemically, the yeast strains did not result in significant differences in the main wine parameters, while some differences in their macromolecular contents and sensory characteristics were noticeable. 37238813 6 28 theme foam 1117:1120 arg1 stability 1122:1130 the foam stability 1113:1130 the foam stability 1113:1130 The foamability was mostly unaffected by the strain used; however, some effect on the foam stability was noticeable, likely due to the differences in polysaccharides released into the wines by the yeast strains. 37238813 5 29 theme sensory 990:996 arg1 characteristics 998:1012 sensory characteristics 990:1012 sensory characteristics 990:1012 Chemically, the yeast strains did not result in significant differences in the main wine parameters, while some differences in their macromolecular contents and sensory characteristics were noticeable. 37238813 3 30 theme sensorial 449:457 arg1 impacts 459:465 the chemical and sensorial impacts 432:465 the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF 432:517 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 0 31 theme Interspecific 10:22 arg1 Hybrids 30:36 Interspecific Yeast Hybrids 10:36 Interspecific Yeast Hybrids 10:36 Effect of Interspecific Yeast Hybrids for Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines. 37238813 5 32 theme wine 913:916 arg1 parameters 918:927 the main wine parameters 904:927 the main wine parameters 904:927 Chemically, the yeast strains did not result in significant differences in the main wine parameters, while some differences in their macromolecular contents and sensory characteristics were noticeable. 37238813 3 33 theme interspecific 629:641 arg1 hybrids 643:649 two commercial and four novel interspecific hybrids 599:649 hybrids 643:649 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 3 34 theme yeast 495:499 arg1 hybrids 501:507 interspecific yeast hybrids 481:507 interspecific yeast hybrids 481:507 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 2 35 from advances 252:259 arg1 programs 282:289 yeast development programs 264:289 yeast development programs 264:289 Recently, advances in yeast development programs have yielded new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas. 37238813 1 36 theme secondary 190:198 arg1 SiBAF 234:238 SiBAF 234:238 SiBAF 234:238 In sparkling winemaking, only a few yeast strains are regularly used for the secondary in-bottle alcoholic fermentation (SiBAF). 37238813 1 36 theme secondary 190:198 arg1 fermentation 220:231 the secondary in-bottle alcoholic fermentation 186:231 the secondary in-bottle alcoholic fermentation (SiBAF) 186:239 In sparkling winemaking, only a few yeast strains are regularly used for the secondary in-bottle alcoholic fermentation (SiBAF). 37238813 3 37 theme interspecific 481:493 arg1 hybrids 501:507 interspecific yeast hybrids 481:507 interspecific yeast hybrids 481:507 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 7 38 theme different 1263:1271 arg1 characteristics 1281:1295 different sensory characteristics 1263:1295 different sensory characteristics 1263:1295 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 8 39 with wines 1590:1594 arg1 flavor 1627:1632 flavor 1627:1632 flavor 1627:1632 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 8 39 with wines 1590:1594 arg1 attributes 1644:1653 aroma attributes 1638:1653 aroma attributes 1638:1653 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 8 39 with wines 1590:1594 arg1 characteristics 1610:1624 chemical characteristics 1601:1624 chemical characteristics 1601:1624 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 3 40 theme chemical 436:443 arg1 impacts 459:465 the chemical and sensorial impacts 432:465 the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF 432:517 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 4 41 theme resulting 795:803 arg1 wines 808:812 the resulting 13 wines 791:812 the resulting 13 wines 791:812 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 1 42 theme in-bottle 200:208 arg1 SiBAF 234:238 SiBAF 234:238 SiBAF 234:238 In sparkling winemaking, only a few yeast strains are regularly used for the secondary in-bottle alcoholic fermentation (SiBAF). 37238813 1 42 theme in-bottle 200:208 arg1 fermentation 220:231 the secondary in-bottle alcoholic fermentation 186:231 the secondary in-bottle alcoholic fermentation (SiBAF) 186:239 In sparkling winemaking, only a few yeast strains are regularly used for the secondary in-bottle alcoholic fermentation (SiBAF). 37238813 0 43 theme Hybrids 30:36 arg1 Effect 0:5 Effect 0:5 Effect of Interspecific Yeast Hybrids for Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines. 0:111 Effect of Interspecific Yeast Hybrids for Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines. 37238813 7 44 theme overall 1345:1351 arg1 liking 1353:1358 overall liking 1345:1358 overall liking 1345:1358 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 1 45 theme alcoholic 210:218 arg1 SiBAF 234:238 SiBAF 234:238 SiBAF 234:238 In sparkling winemaking, only a few yeast strains are regularly used for the secondary in-bottle alcoholic fermentation (SiBAF). 37238813 1 45 theme alcoholic 210:218 arg1 fermentation 220:231 the secondary in-bottle alcoholic fermentation 186:231 the secondary in-bottle alcoholic fermentation (SiBAF) 186:239 In sparkling winemaking, only a few yeast strains are regularly used for the secondary in-bottle alcoholic fermentation (SiBAF). 37238813 0 46 theme In-Bottle 52:60 arg1 Fermentation 72:83 Secondary In-Bottle Alcoholic Fermentation 42:83 Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines 42:110 Effect of Interspecific Yeast Hybrids for Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines. 37238813 3 47 theme novel 623:627 arg1 hybrids 643:649 two commercial and four novel interspecific hybrids 599:649 hybrids 643:649 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 4 48 theme wines 808:812 arg1 properties 777:786 sensory properties 769:786 sensory properties 769:786 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 4 48 theme wines 808:812 arg1 foaming 746:752 foaming 746:752 foaming 746:752 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 4 48 theme wines 808:812 arg1 composition 715:725 the chemical and macromolecular composition 683:725 composition 715:725 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 4 48 theme wines 808:812 arg1 profile 737:743 phenolic profile 728:743 phenolic profile 728:743 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 4 48 theme wines 808:812 arg1 viscosity 755:763 viscosity 755:763 viscosity 755:763 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 8 49 theme commercial 1689:1698 arg1 strains 1725:1731 commonly used commercial Saccharomyces cerevisiae strains 1675:1731 commonly used commercial Saccharomyces cerevisiae strains 1675:1731 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 1 50 theme sparkling 116:124 arg1 winemaking 126:135 sparkling winemaking 116:135 sparkling winemaking 116:135 In sparkling winemaking, only a few yeast strains are regularly used for the secondary in-bottle alcoholic fermentation (SiBAF). 37238813 0 51 theme Secondary 42:50 arg1 Fermentation 72:83 Secondary In-Bottle Alcoholic Fermentation 42:83 Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines 42:110 Effect of Interspecific Yeast Hybrids for Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines. 37238813 8 52 used used 1528:1531 arg2 hybrids 1513:1519 Novel interspecific yeast hybrids 1487:1519 Novel interspecific yeast hybrids 1487:1519 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 7 53 theme finish 1337:1342 arg1 terms 1300:1304 terms 1300:1304 terms of aroma and bouquet, balance, finish, overall liking and preference 1300:1373 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 2 54 theme wine 332:335 arg1 hybrids 343:349 interspecific wine yeast hybrids 318:349 interspecific wine yeast hybrids 318:349 Recently, advances in yeast development programs have yielded new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas. 37238813 4 55 theme chemical 687:694 arg1 composition 715:725 the chemical and macromolecular composition 683:725 composition 715:725 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 8 56 theme used 1684:1687 arg1 strains 1725:1731 commonly used commercial Saccharomyces cerevisiae strains 1675:1731 commonly used commercial Saccharomyces cerevisiae strains 1675:1731 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 4 57 theme sensory 769:775 arg1 properties 777:786 sensory properties 769:786 sensory properties 769:786 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 6 58 from effect 1103:1108 arg1 stability 1122:1130 the foam stability 1113:1130 the foam stability 1113:1130 The foamability was mostly unaffected by the strain used; however, some effect on the foam stability was noticeable, likely due to the differences in polysaccharides released into the wines by the yeast strains. 37238813 2 59 theme interspecific 318:330 arg1 hybrids 343:349 interspecific wine yeast hybrids 318:349 interspecific wine yeast hybrids 318:349 Recently, advances in yeast development programs have yielded new breeds of interspecific wine yeast hybrids that ferment efficiently while producing novel flavors and aromas. 37238813 7 60 theme liking 1353:1358 arg1 terms 1300:1304 terms 1300:1304 terms of aroma and bouquet, balance, finish, overall liking and preference 1300:1373 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 8 61 theme cerevisiae 1714:1723 arg1 strains 1725:1731 commonly used commercial Saccharomyces cerevisiae strains 1675:1731 commonly used commercial Saccharomyces cerevisiae strains 1675:1731 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 5 62 theme significant 877:887 arg1 differences 889:899 significant differences 877:899 significant differences in the main wine parameters 877:927 Chemically, the yeast strains did not result in significant differences in the main wine parameters, while some differences in their macromolecular contents and sensory characteristics were noticeable. 37238813 1 63 used used 177:180 arg2 strains 155:161 only a few yeast strains 138:161 only a few yeast strains 138:161 In sparkling winemaking, only a few yeast strains are regularly used for the secondary in-bottle alcoholic fermentation (SiBAF). 37238813 4 64 theme phenolic 728:735 arg1 profile 737:743 phenolic profile 728:743 phenolic profile 728:743 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 8 65 theme chemical 1601:1608 arg1 characteristics 1610:1624 chemical characteristics 1601:1624 chemical characteristics 1601:1624 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 4 66 theme macromolecular 700:713 arg1 composition 715:725 the chemical and macromolecular composition 683:725 composition 715:725 After 12 months of lees aging, the chemical and macromolecular composition, phenolic profile, foaming, viscosity and sensory properties of the resulting 13 wines were assessed. 37238813 6 67 from differences 1166:1176 arg1 polysaccharides 1181:1195 polysaccharides 1181:1195 polysaccharides released into the wines by the yeast strains 1181:1240 The foamability was mostly unaffected by the strain used; however, some effect on the foam stability was noticeable, likely due to the differences in polysaccharides released into the wines by the yeast strains. 37238813 7 68 theme sensory 1273:1279 arg1 characteristics 1281:1295 different sensory characteristics 1263:1295 different sensory characteristics 1263:1295 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 3 69 theme hybrids 501:507 arg1 use 474:476 the use 470:476 the use of interspecific yeast hybrids for SiBAF 470:517 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 7 70 theme aroma 1309:1313 arg1 terms 1300:1304 terms 1300:1304 terms of aroma and bouquet, balance, finish, overall liking and preference 1300:1373 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 8 71 theme sparkling 1556:1564 arg1 wines 1566:1570 sparkling wines 1556:1570 sparkling wines 1556:1570 Novel interspecific yeast hybrids can be used for the elaboration of sparkling wines, as they provided wines with chemical characteristics, flavor and aroma attributes similar to those of commonly used commercial Saccharomyces cerevisiae strains. 37238813 0 72 theme Alcoholic 62:70 arg1 Fermentation 72:83 Secondary In-Bottle Alcoholic Fermentation 42:83 Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines 42:110 Effect of Interspecific Yeast Hybrids for Secondary In-Bottle Alcoholic Fermentation of English Sparkling Wines. 37238813 7 73 theme base 1437:1440 arg1 wines 1442:1446 the base wines 1433:1446 the base wines rather than the strain used for SiBAF 1433:1484 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 7 74 theme bouquet 1319:1325 arg1 terms 1300:1304 terms 1300:1304 terms of aroma and bouquet, balance, finish, overall liking and preference 1300:1373 The wines exhibited different sensory characteristics in terms of aroma and bouquet, balance, finish, overall liking and preference, but these were mostly attributable to the differences in the base wines rather than the strain used for SiBAF. 37238813 3 75 theme base 563:566 arg1 wines 568:572 three commercial English base wines 538:572 three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids 538:649 In this work, the chemical and sensorial impacts of the use of interspecific yeast hybrids for SiBAF were studied using three commercial English base wines prepared for SiBAF using two commercial and four novel interspecific hybrids. 37238813 5 76 from differences 941:951 arg1 contents 977:984 their macromolecular contents 956:984 their macromolecular contents 956:984 Chemically, the yeast strains did not result in significant differences in the main wine parameters, while some differences in their macromolecular contents and sensory characteristics were noticeable. 37238813 5 76 from differences 941:951 arg1 characteristics 998:1012 sensory characteristics 990:1012 sensory characteristics 990:1012 Chemically, the yeast strains did not result in significant differences in the main wine parameters, while some differences in their macromolecular contents and sensory characteristics were noticeable. 36276816 0 0 theme gut 106:108 arg1 microbiota 110:119 gut microbiota 106:119 gut microbiota 106:119 Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. 36276816 5 1 theme microbiota 729:738 arg1 composition 740:750 gut microbiota composition 725:750 gut microbiota composition 725:750 We also determined an improvement in gut microbiota composition by 16sRNA pyrosequencing. 36276816 8 2 dep proteins 1325:1332 arg1 ZO-1 1354:1357 ZO-1 1354:1357 ZO-1 1354:1357 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 2 dep proteins 1325:1332 arg1 occludin 1361:1368 occludin 1361:1368 occludin 1361:1368 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 2 dep proteins 1325:1332 arg1 protein 1394:1400 mucin-2 protein 1386:1400 mucin-2 protein (MUC2) 1386:1407 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 2 dep proteins 1325:1332 arg1 proteins 1325:1332 the colon tight-junction proteins 1300:1332 the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2) 1300:1407 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 2 dep proteins 1325:1332 arg1 MUC2 1403:1406 MUC2 1403:1406 MUC2 1403:1406 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 2 dep proteins 1325:1332 arg1 occludens-1 1341:1351 zonula occludens-1 1334:1351 zonula occludens-1 (ZO-1) 1334:1358 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 2 dep proteins 1325:1332 arg1 claudin-1 1371:1379 claudin-1 1371:1379 claudin-1 1371:1379 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 3 theme tight-junction 1310:1323 arg1 occludens-1 1341:1351 zonula occludens-1 1334:1351 zonula occludens-1 (ZO-1) 1334:1358 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 3 theme tight-junction 1310:1323 arg1 protein 1394:1400 mucin-2 protein 1386:1400 mucin-2 protein (MUC2) 1386:1407 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 3 theme tight-junction 1310:1323 arg1 proteins 1325:1332 the colon tight-junction proteins 1300:1332 the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2) 1300:1407 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 3 theme tight-junction 1310:1323 arg1 claudin-1 1371:1379 claudin-1 1371:1379 claudin-1 1371:1379 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 3 theme tight-junction 1310:1323 arg1 occludin 1361:1368 occludin 1361:1368 occludin 1361:1368 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 1 4 theme economic 234:241 arg1 problems 243:250 serious worldwide economic problems 216:250 serious worldwide economic problems 216:250 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 36276816 6 5 dep bacteria 918:925 arg1 bacteria 918:925 the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia 900:972 the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia 900:972 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 6 5 dep bacteria 918:925 arg1 Corynebacterium 943:957 Corynebacterium 943:957 Corynebacterium 943:957 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 6 5 dep bacteria 918:925 arg1 Facklamia 964:972 Facklamia 964:972 Facklamia 964:972 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 6 5 dep bacteria 918:925 arg1 Actinobacteria 927:940 Actinobacteria 927:940 Actinobacteria 927:940 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 1 6 theme diabetes 161:168 arg1 T2DM 180:183 T2DM 180:183 T2DM 180:183 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 36276816 1 6 theme diabetes 161:168 arg1 mellitus 170:177 Type 2 diabetes mellitus 154:177 Type 2 diabetes mellitus (T2DM) 154:184 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 36276816 1 6 theme diabetes 161:168 arg1 issue 198:202 a health issue 189:202 a health issue that causes serious worldwide economic problems 189:250 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 36276816 3 7 from diet 508:511 arg1 mice 567:570 BALB/c mice 560:570 BALB/c mice 560:570 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 9 8 theme T2DM 1494:1497 arg1 mice 1499:1502 T2DM mice 1494:1502 T2DM mice 1494:1502 Additionally, MEP administration affects the metagenome of microbial communities in T2DM mice by altering the functional metabolic pathways. 36276816 10 9 from metabolites 1671:1681 arg1 T2DM 1686:1689 T2DM 1686:1689 T2DM 1686:1689 All these findings suggested that MEP is a beneficial prebiotic associated with ameliorating the gut microbiota and its metabolites in T2DM. 36276816 8 10 theme zonula 1334:1339 arg1 occludens-1 1341:1351 zonula occludens-1 1334:1351 zonula occludens-1 (ZO-1) 1334:1358 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 10 theme zonula 1334:1339 arg1 proteins 1325:1332 the colon tight-junction proteins 1300:1332 the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2) 1300:1407 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 10 theme zonula 1334:1339 arg1 ZO-1 1354:1357 ZO-1 1354:1357 ZO-1 1354:1357 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 7 11 with treatment 1002:1010 arg1 MEP 1030:1032 MEP 1030:1032 MEP 1030:1032 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 10 12 from microbiota 1652:1661 arg1 T2DM 1686:1689 T2DM 1686:1689 T2DM 1686:1689 All these findings suggested that MEP is a beneficial prebiotic associated with ameliorating the gut microbiota and its metabolites in T2DM. 36276816 8 13 theme proteins 1325:1332 arg1 expression 1286:1295 the expression 1282:1295 the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2) 1282:1407 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 3 14 from T2DM 552:555 arg1 mice 567:570 BALB/c mice 560:570 BALB/c mice 560:570 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 9 15 theme communities 1479:1489 arg1 metagenome 1455:1464 the metagenome 1451:1464 the metagenome of microbial communities in T2DM mice 1451:1502 Additionally, MEP administration affects the metagenome of microbial communities in T2DM mice by altering the functional metabolic pathways. 36276816 0 16 theme type 126:129 arg1 model 147:151 a type 2 diabetic mice model 124:151 a type 2 diabetic mice model 124:151 Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. 36276816 7 17 theme resistance-related 1078:1095 arg1 interleukin 1124:1134 interleukin 1β 1124:1137 interleukin 1β (IL-1β) 1124:1145 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 17 theme resistance-related 1078:1095 arg1 interleukin 1189:1199 interleukin 6 1189:1201 interleukin 6 (IL-6) 1189:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 17 theme resistance-related 1078:1095 arg1 cytokines 1114:1122 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 17 theme resistance-related 1078:1095 arg1 factor-alpha 1163:1174 tumor necrosis factor-alpha 1148:1174 tumor necrosis factor-alpha (TNF-α) 1148:1182 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 9 18 theme functional 1520:1529 arg1 pathways 1541:1548 the functional metabolic pathways 1516:1548 the functional metabolic pathways 1516:1548 Additionally, MEP administration affects the metagenome of microbial communities in T2DM mice by altering the functional metabolic pathways. 36276816 6 19 with Treatment 778:786 arg1 MEP 793:795 MEP 793:795 MEP 793:795 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 7 20 theme pro-inflammatory 1097:1112 arg1 interleukin 1124:1134 interleukin 1β 1124:1137 interleukin 1β (IL-1β) 1124:1145 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 20 theme pro-inflammatory 1097:1112 arg1 interleukin 1189:1199 interleukin 6 1189:1201 interleukin 6 (IL-6) 1189:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 20 theme pro-inflammatory 1097:1112 arg1 cytokines 1114:1122 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 20 theme pro-inflammatory 1097:1112 arg1 factor-alpha 1163:1174 tumor necrosis factor-alpha 1148:1174 tumor necrosis factor-alpha (TNF-α) 1148:1182 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 3 21 theme high-fat 499:506 arg1 diet 508:511 a high-fat diet 497:511 a high-fat diet (HFD) 497:517 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 3 21 theme high-fat 499:506 arg1 HFD 514:516 HFD 514:516 HFD 514:516 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 4 22 theme MEP 595:597 arg1 administration 577:590 The administration 573:590 The administration of MEP 573:597 The administration of MEP effectively regulated hyperglycemia and hyperlipidemia and improved insulin sensitivity. 36276816 0 23 theme esculenta 10:18 arg1 polysaccharide 29:42 Morchella esculenta mushroom polysaccharide 0:42 Morchella esculenta mushroom polysaccharide 0:42 Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. 36276816 9 24 theme metabolic 1531:1539 arg1 pathways 1541:1548 the functional metabolic pathways 1516:1548 the functional metabolic pathways 1516:1548 Additionally, MEP administration affects the metagenome of microbial communities in T2DM mice by altering the functional metabolic pathways. 36276816 8 25 theme MEP 1221:1223 arg1 treatment 1225:1233 MEP treatment 1221:1233 MEP treatment 1221:1233 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 0 26 theme Morchella 0:8 arg1 polysaccharide 29:42 Morchella esculenta mushroom polysaccharide 0:42 Morchella esculenta mushroom polysaccharide 0:42 Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. 36276816 7 27 theme tumor 1148:1152 arg1 factor-alpha 1163:1174 tumor necrosis factor-alpha 1148:1174 tumor necrosis factor-alpha (TNF-α) 1148:1182 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 27 theme tumor 1148:1152 arg1 cytokines 1114:1122 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 27 theme tumor 1148:1152 arg1 TNF-α 1177:1181 TNF-α 1177:1181 TNF-α 1177:1181 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 28 theme insulin 1070:1076 arg1 interleukin 1124:1134 interleukin 1β 1124:1137 interleukin 1β (IL-1β) 1124:1145 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 28 theme insulin 1070:1076 arg1 interleukin 1189:1199 interleukin 6 1189:1201 interleukin 6 (IL-6) 1189:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 28 theme insulin 1070:1076 arg1 cytokines 1114:1122 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 28 theme insulin 1070:1076 arg1 factor-alpha 1163:1174 tumor necrosis factor-alpha 1148:1174 tumor necrosis factor-alpha (TNF-α) 1148:1182 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 9 29 from metagenome 1455:1464 arg1 mice 1499:1502 T2DM mice 1494:1502 T2DM mice 1494:1502 Additionally, MEP administration affects the metagenome of microbial communities in T2DM mice by altering the functional metabolic pathways. 36276816 5 30 from improvement 710:720 arg1 composition 740:750 gut microbiota composition 725:750 gut microbiota composition 725:750 We also determined an improvement in gut microbiota composition by 16sRNA pyrosequencing. 36276816 7 31 theme necrosis 1154:1161 arg1 factor-alpha 1163:1174 tumor necrosis factor-alpha 1148:1174 tumor necrosis factor-alpha (TNF-α) 1148:1182 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 31 theme necrosis 1154:1161 arg1 cytokines 1114:1122 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 31 theme necrosis 1154:1161 arg1 TNF-α 1177:1181 TNF-α 1177:1181 TNF-α 1177:1181 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 0 32 theme diabetic 133:140 arg1 model 147:151 a type 2 diabetic mice model 124:151 a type 2 diabetic mice model 124:151 Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. 36276816 2 33 theme natural 290:296 arg1 polysaccharides 298:312 natural polysaccharides 290:312 natural polysaccharides 290:312 It has previously been reported that natural polysaccharides have been studied with regard to regulating the gut microbiota, which plays an important role in T2DM. 36276816 9 34 theme MEP 1424:1426 arg1 administration 1428:1441 MEP administration 1424:1441 MEP administration 1424:1441 Additionally, MEP administration affects the metagenome of microbial communities in T2DM mice by altering the functional metabolic pathways. 36276816 0 35 theme mushroom 20:27 arg1 polysaccharide 29:42 Morchella esculenta mushroom polysaccharide 0:42 Morchella esculenta mushroom polysaccharide 0:42 Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. 36276816 7 36 theme endotoxemia 1054:1064 arg1 interleukin 1124:1134 interleukin 1β 1124:1137 interleukin 1β (IL-1β) 1124:1145 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 36 theme endotoxemia 1054:1064 arg1 interleukin 1189:1199 interleukin 6 1189:1201 interleukin 6 (IL-6) 1189:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 36 theme endotoxemia 1054:1064 arg1 cytokines 1114:1122 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 36 theme endotoxemia 1054:1064 arg1 factor-alpha 1163:1174 tumor necrosis factor-alpha 1148:1174 tumor necrosis factor-alpha (TNF-α) 1148:1182 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 8 37 theme colon 1304:1308 arg1 occludens-1 1341:1351 zonula occludens-1 1334:1351 zonula occludens-1 (ZO-1) 1334:1358 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 37 theme colon 1304:1308 arg1 protein 1394:1400 mucin-2 protein 1386:1400 mucin-2 protein (MUC2) 1386:1407 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 37 theme colon 1304:1308 arg1 proteins 1325:1332 the colon tight-junction proteins 1300:1332 the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2) 1300:1407 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 37 theme colon 1304:1308 arg1 claudin-1 1371:1379 claudin-1 1371:1379 claudin-1 1371:1379 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 37 theme colon 1304:1308 arg1 occludin 1361:1368 occludin 1361:1368 occludin 1361:1368 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 6 38 from increase 807:814 arg1 bacteria 830:837 beneficial bacteria 819:837 beneficial bacteria 819:837 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 4 39 theme insulin 667:673 arg1 sensitivity 675:685 insulin sensitivity 667:685 insulin sensitivity 667:685 The administration of MEP effectively regulated hyperglycemia and hyperlipidemia and improved insulin sensitivity. 36276816 1 40 theme health 191:196 arg1 mellitus 170:177 Type 2 diabetes mellitus 154:177 Type 2 diabetes mellitus (T2DM) 154:184 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 36276816 1 40 theme health 191:196 arg1 issue 198:202 a health issue 189:202 a health issue that causes serious worldwide economic problems 189:250 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 36276816 2 41 theme important 393:401 arg1 role 403:406 an important role 390:406 an important role 390:406 It has previously been reported that natural polysaccharides have been studied with regard to regulating the gut microbiota, which plays an important role in T2DM. 36276816 5 42 theme 16sRNA 755:760 arg1 pyrosequencing 762:775 16sRNA pyrosequencing 755:775 16sRNA pyrosequencing 755:775 We also determined an improvement in gut microbiota composition by 16sRNA pyrosequencing. 36276816 0 43 theme mice 142:145 arg1 model 147:151 a type 2 diabetic mice model 124:151 a type 2 diabetic mice model 124:151 Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. 36276816 0 44 from permeability 89:100 arg1 model 147:151 a type 2 diabetic mice model 124:151 a type 2 diabetic mice model 124:151 Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. 36276816 3 45 theme -induced 543:550 arg1 T2DM 552:555 streptozotocin (STZ)-induced T2DM 523:555 streptozotocin (STZ)-induced T2DM in BALB/c mice 523:570 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 8 46 theme intestinal 1244:1253 arg1 permeability 1255:1266 intestinal permeability 1244:1266 intestinal permeability 1244:1266 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 6 47 theme bacteria 918:925 arg1 proportion 886:895 the proportion 882:895 the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia 882:972 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 5 48 theme gut 725:727 arg1 composition 740:750 gut microbiota composition 725:750 gut microbiota composition 725:750 We also determined an improvement in gut microbiota composition by 16sRNA pyrosequencing. 36276816 3 49 theme esculenta 463:471 arg1 MEP 489:491 MEP 489:491 MEP 489:491 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 3 49 theme esculenta 463:471 arg1 polysaccharide 473:486 Morchella esculenta polysaccharide 453:486 Morchella esculenta polysaccharide (MEP) 453:492 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 7 50 dep cytokines 1114:1122 arg1 interleukin 1124:1134 interleukin 1β 1124:1137 interleukin 1β (IL-1β) 1124:1145 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 50 dep cytokines 1114:1122 arg1 interleukin 1189:1199 interleukin 6 1189:1201 interleukin 6 (IL-6) 1189:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 50 dep cytokines 1114:1122 arg1 factor-alpha 1163:1174 tumor necrosis factor-alpha 1148:1174 tumor necrosis factor-alpha (TNF-α) 1148:1182 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 50 dep cytokines 1114:1122 arg1 TNF-α 1177:1181 TNF-α 1177:1181 TNF-α 1177:1181 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 50 dep cytokines 1114:1122 arg1 IL-1β 1140:1144 IL-1β 1140:1144 IL-1β 1140:1144 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 50 dep cytokines 1114:1122 arg1 IL-6 1204:1207 IL-6 1204:1207 IL-6 1204:1207 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 50 dep cytokines 1114:1122 arg1 cytokines 1114:1122 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 6 51 theme opportunistic 904:916 arg1 bacteria 918:925 the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia 900:972 the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia 900:972 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 6 51 theme opportunistic 904:916 arg1 Corynebacterium 943:957 Corynebacterium 943:957 Corynebacterium 943:957 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 6 51 theme opportunistic 904:916 arg1 Facklamia 964:972 Facklamia 964:972 Facklamia 964:972 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 6 51 theme opportunistic 904:916 arg1 Actinobacteria 927:940 Actinobacteria 927:940 Actinobacteria 927:940 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 7 52 theme reduced 1046:1052 arg1 interleukin 1124:1134 interleukin 1β 1124:1137 interleukin 1β (IL-1β) 1124:1145 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 52 theme reduced 1046:1052 arg1 interleukin 1189:1199 interleukin 6 1189:1201 interleukin 6 (IL-6) 1189:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 52 theme reduced 1046:1052 arg1 cytokines 1114:1122 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) 1046:1208 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 7 52 theme reduced 1046:1052 arg1 factor-alpha 1163:1174 tumor necrosis factor-alpha 1148:1174 tumor necrosis factor-alpha (TNF-α) 1148:1182 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 6 53 theme beneficial 819:828 arg1 bacteria 830:837 beneficial bacteria 819:837 beneficial bacteria 819:837 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 3 54 theme polysaccharide 473:486 arg1 effects 442:448 the effects 438:448 the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice 438:570 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 7 55 theme T2DM 1015:1018 arg1 mice 1020:1023 T2DM mice 1015:1023 T2DM mice 1015:1023 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 3 56 theme BALB/c 560:565 arg1 mice 567:570 BALB/c mice 560:570 BALB/c mice 560:570 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 3 57 from effects 442:448 arg1 diet 508:511 a high-fat diet 497:511 a high-fat diet (HFD) 497:517 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 3 57 from effects 442:448 arg1 HFD 514:516 HFD 514:516 HFD 514:516 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 3 57 from effects 442:448 arg1 T2DM 552:555 streptozotocin (STZ)-induced T2DM 523:555 streptozotocin (STZ)-induced T2DM in BALB/c mice 523:570 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 9 58 theme microbial 1469:1477 arg1 communities 1479:1489 microbial communities 1469:1489 microbial communities 1469:1489 Additionally, MEP administration affects the metagenome of microbial communities in T2DM mice by altering the functional metabolic pathways. 36276816 7 59 theme mice 1020:1023 arg1 treatment 1002:1010 the treatment 998:1010 the treatment of T2DM mice with MEP 998:1032 Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). 36276816 8 60 theme mucin-2 1386:1392 arg1 protein 1394:1400 mucin-2 protein 1386:1400 mucin-2 protein (MUC2) 1386:1407 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 60 theme mucin-2 1386:1392 arg1 proteins 1325:1332 the colon tight-junction proteins 1300:1332 the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2) 1300:1407 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 8 60 theme mucin-2 1386:1392 arg1 MUC2 1403:1406 MUC2 1403:1406 MUC2 1403:1406 Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). 36276816 10 61 theme gut 1648:1650 arg1 microbiota 1652:1661 the gut microbiota 1644:1661 the gut microbiota 1644:1661 All these findings suggested that MEP is a beneficial prebiotic associated with ameliorating the gut microbiota and its metabolites in T2DM. 36276816 3 62 theme Morchella 453:461 arg1 MEP 489:491 MEP 489:491 MEP 489:491 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 3 62 theme Morchella 453:461 arg1 polysaccharide 473:486 Morchella esculenta polysaccharide 453:486 Morchella esculenta polysaccharide (MEP) 453:492 Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. 36276816 6 63 dep Lactobacillus 846:858 arg1 i.e. 840:843 i.e. 840:843 i.e. 840:843 Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. 36276816 0 64 from microbiota 110:119 arg1 model 147:151 a type 2 diabetic mice model 124:151 a type 2 diabetic mice model 124:151 Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. 36276816 2 65 theme gut 362:364 arg1 microbiota 366:375 the gut microbiota 358:375 the gut microbiota 358:375 It has previously been reported that natural polysaccharides have been studied with regard to regulating the gut microbiota, which plays an important role in T2DM. 36276816 1 66 theme serious 216:222 arg1 problems 243:250 serious worldwide economic problems 216:250 serious worldwide economic problems 216:250 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 36276816 0 67 theme intestinal 78:87 arg1 permeability 89:100 intestinal permeability 78:100 intestinal permeability 78:100 Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. 36276816 1 68 theme Type 154:157 arg1 T2DM 180:183 T2DM 180:183 T2DM 180:183 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 36276816 1 68 theme Type 154:157 arg1 mellitus 170:177 Type 2 diabetes mellitus 154:177 Type 2 diabetes mellitus (T2DM) 154:184 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 36276816 1 68 theme Type 154:157 arg1 issue 198:202 a health issue 189:202 a health issue that causes serious worldwide economic problems 189:250 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 36276816 10 69 theme beneficial 1594:1603 arg1 MEP 1585:1587 MEP 1585:1587 MEP 1585:1587 All these findings suggested that MEP is a beneficial prebiotic associated with ameliorating the gut microbiota and its metabolites in T2DM. 36276816 10 69 theme beneficial 1594:1603 arg1 prebiotic 1605:1613 a beneficial prebiotic 1592:1613 a beneficial prebiotic associated with ameliorating the gut microbiota and its metabolites in T2DM 1592:1689 All these findings suggested that MEP is a beneficial prebiotic associated with ameliorating the gut microbiota and its metabolites in T2DM. 36276816 1 70 theme worldwide 224:232 arg1 problems 243:250 serious worldwide economic problems 216:250 serious worldwide economic problems 216:250 Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. 35860528 12 0 theme other 1979:1983 arg1 crops 1985:1989 other crops 1979:1989 other crops such as maize 1979:2003 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 12 0 theme other 1979:1983 arg1 maize 1999:2003 maize 1999:2003 maize 1999:2003 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 8 1 theme transgenic 1173:1182 arg1 poplars 1184:1190 transgenic poplars 1173:1190 transgenic poplars 1173:1190 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 4 2 theme alkaline 701:708 arg1 pretreatment 710:721 alkaline pretreatment 701:721 alkaline pretreatment 701:721 The resulting transgenic plants did not suffer from yield penalties and had an increased saccharification yield after alkaline pretreatment. 35860528 6 3 theme CURS2 834:838 arg1 expression 812:821 the heterologous expression 795:821 the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B) 795:929 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 11 4 theme translational 1748:1760 arg1 research 1762:1769 translational research 1748:1769 translational research in crops 1748:1778 These differences in (growth) phenotype illustrate that translational research in crops is essential to assess the value of an engineering strategy for applications. 35860528 6 5 theme DCS 826:828 arg1 expression 812:821 the heterologous expression 795:821 the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B) 795:929 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 12 6 theme specific 1925:1932 arg1 promoters 1934:1942 more specific promoters 1920:1942 more specific promoters 1920:1942 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 4 7 theme increased 662:670 arg1 yield 689:693 an increased saccharification yield 659:693 an increased saccharification yield 659:693 The resulting transgenic plants did not suffer from yield penalties and had an increased saccharification yield after alkaline pretreatment. 35860528 12 8 dep lead 2012:2015 arg1 e.g. 1905:1908 e.g. 1905:1908 e.g. 1905:1908 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 7 9 theme yield 1104:1108 arg1 penalties 1110:1118 yield penalties 1104:1118 yield penalties 1104:1118 ProCesA8-B:DCS_CURS2 transgenic poplars, however, suffered from shoot-tip necrosis and yield penalties. 35860528 9 10 theme p-hydroxyphenyl 1436:1450 arg1 units 1456:1460 p-hydroxyphenyl (H) units 1436:1460 p-hydroxyphenyl (H) units 1436:1460 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 8 11 theme cellulose 1205:1213 arg1 % 1198:1198 21% 1196:1198 21% less cellulose 1196:1213 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 6 12 theme lignified 985:993 arg1 walls 1000:1004 the lignified cell walls 981:1004 the lignified cell walls of poplar 981:1014 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 8 13 theme more 1253:1256 arg1 lignin 1258:1263 more lignin 1253:1263 23% more lignin 1249:1263 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 10 14 theme hot 1583:1585 arg1 pretreatment 1593:1604 alkaline or hot water pretreatment 1571:1604 pretreatment 1593:1604 Without, or with alkaline or hot water pretreatment, the saccharification efficiency of the transgenic lines was equal to that of the WT. 35860528 2 15 theme traditional 247:257 arg1 monomers 266:273 traditional lignin monomers 247:273 traditional lignin monomers 247:273 By engineering plants to partially replace traditional lignin monomers with alternative ones, lignin degradability and extractability can be enhanced. 35860528 9 16 theme H 1453:1453 arg1 units 1456:1460 p-hydroxyphenyl (H) units 1436:1460 p-hydroxyphenyl (H) units 1436:1460 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 10 17 theme alkaline 1571:1578 arg1 pretreatment 1593:1604 alkaline or hot water pretreatment 1571:1604 pretreatment 1593:1604 Without, or with alkaline or hot water pretreatment, the saccharification efficiency of the transgenic lines was equal to that of the WT. 35860528 7 18 theme DCS_CURS2 1028:1036 arg1 poplars 1049:1055 ProCesA8-B:DCS_CURS2 transgenic poplars 1017:1055 ProCesA8-B:DCS_CURS2 transgenic poplars 1017:1055 ProCesA8-B:DCS_CURS2 transgenic poplars, however, suffered from shoot-tip necrosis and yield penalties. 35860528 9 19 theme units 1456:1460 arg1 frequency 1475:1483 a decreased frequency 1463:1483 a decreased frequency of p-hydroxybenzoates 1463:1505 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 19 theme units 1456:1460 arg1 frequency 1423:1431 an increased frequency 1410:1431 an increased frequency of p-hydroxyphenyl (H) units 1410:1460 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 19 theme units 1456:1460 arg1 fraction 1520:1527 a higher fraction 1511:1527 a higher fraction of phenylcoumaran units 1511:1551 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 19 theme units 1456:1460 arg1 ratio 1403:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 11 20 from differences 1698:1708 arg1 phenotype 1722:1730 (growth) phenotype 1713:1730 (growth) phenotype 1713:1730 These differences in (growth) phenotype illustrate that translational research in crops is essential to assess the value of an engineering strategy for applications. 35860528 4 21 contain had 655:657 arg2 yield 689:693 an increased saccharification yield 659:693 an increased saccharification yield 659:693 The resulting transgenic plants did not suffer from yield penalties and had an increased saccharification yield after alkaline pretreatment. 35860528 4 21 contain had 655:657 arg1 plants 608:613 The resulting transgenic plants 583:613 The resulting transgenic plants 583:613 The resulting transgenic plants did not suffer from yield penalties and had an increased saccharification yield after alkaline pretreatment. 35860528 7 22 theme ProCesA8-B 1017:1026 arg1 poplars 1049:1055 ProCesA8-B:DCS_CURS2 transgenic poplars 1017:1055 ProCesA8-B:DCS_CURS2 transgenic poplars 1017:1055 ProCesA8-B:DCS_CURS2 transgenic poplars, however, suffered from shoot-tip necrosis and yield penalties. 35860528 8 23 theme lignin 1293:1298 arg1 composition 1300:1310 a significantly altered lignin composition 1269:1310 a significantly altered lignin composition 1269:1310 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 0 24 theme Biomass 70:76 arg1 Yield 78:82 Biomass Yield 70:82 Biomass Yield 70:82 Engineering Curcumin Biosynthesis in Poplar Affects Lignification and Biomass Yield. 35860528 8 25 contain had 1192:1194 arg1 wood 1165:1168 the wood 1161:1168 the wood of transgenic poplars 1161:1190 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 8 25 contain had 1192:1194 arg2 % 1251:1251 23% 1249:1251 23% more lignin 1249:1263 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 8 25 contain had 1192:1194 arg2 composition 1300:1310 a significantly altered lignin composition 1269:1310 a significantly altered lignin composition 1269:1310 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 8 25 contain had 1192:1194 arg2 % 1198:1198 21% 1196:1198 21% less cellulose 1196:1213 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 8 25 contain had 1192:1194 arg2 % 1218:1218 28% 1216:1218 28% more matrix polysaccharides 1216:1246 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 1 26 theme due 173:175 arg1 sugars 159:164 simple sugars 152:164 simple sugars mainly due to the presence of lignin 152:201 Lignocellulosic biomass is recalcitrant toward deconstruction into simple sugars mainly due to the presence of lignin. 35860528 0 27 from Biosynthesis 21:32 arg1 Poplar 37:42 Poplar 37:42 Poplar 37:42 Engineering Curcumin Biosynthesis in Poplar Affects Lignification and Biomass Yield. 35860528 9 28 theme p-hydroxybenzoates 1488:1505 arg1 frequency 1475:1483 a decreased frequency 1463:1483 a decreased frequency of p-hydroxybenzoates 1463:1505 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 28 theme p-hydroxybenzoates 1488:1505 arg1 frequency 1423:1431 an increased frequency 1410:1431 an increased frequency of p-hydroxyphenyl (H) units 1410:1460 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 28 theme p-hydroxybenzoates 1488:1505 arg1 fraction 1520:1527 a higher fraction 1511:1527 a higher fraction of phenylcoumaran units 1511:1551 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 28 theme p-hydroxybenzoates 1488:1505 arg1 ratio 1403:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 2 29 theme alternative 280:290 arg1 ones 292:295 alternative ones 280:295 alternative ones 280:295 By engineering plants to partially replace traditional lignin monomers with alternative ones, lignin degradability and extractability can be enhanced. 35860528 5 30 theme crop 778:781 arg1 poplar 783:788 the bio-energy crop poplar 763:788 the bio-energy crop poplar 763:788 Here, we translated this strategy into the bio-energy crop poplar. 35860528 8 31 dep % 1251:1251 arg1 lignin 1258:1263 more lignin 1253:1263 23% more lignin 1249:1263 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 6 32 theme poplar 1009:1014 arg1 walls 1000:1004 the lignified cell walls 981:1004 the lignified cell walls of poplar 981:1014 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 3 33 theme alternative 371:381 arg1 curcumin 391:398 the alternative monomer curcumin 367:398 the alternative monomer curcumin 367:398 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 3 34 theme Arabidopsis 477:487 arg1 walls 468:472 lignified cell walls 453:472 lignified cell walls of Arabidopsis 453:487 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 1 35 theme Lignocellulosic 85:99 arg1 biomass 101:107 Lignocellulosic biomass 85:107 Lignocellulosic biomass 85:107 Lignocellulosic biomass is recalcitrant toward deconstruction into simple sugars mainly due to the presence of lignin. 35860528 3 36 theme SYNTHASE2 564:572 arg1 expression 509:518 the heterologous expression 492:518 the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2) 492:580 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 0 37 theme Engineering 0:10 arg1 Biosynthesis 21:32 Engineering Curcumin Biosynthesis 0:32 Engineering Curcumin Biosynthesis in Poplar 0:42 Engineering Curcumin Biosynthesis in Poplar Affects Lignification and Biomass Yield. 35860528 9 38 theme phenylcoumaran 1532:1545 arg1 units 1547:1551 phenylcoumaran units 1532:1551 phenylcoumaran units 1532:1551 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 10 39 theme transgenic 1646:1655 arg1 lines 1657:1661 the transgenic lines 1642:1661 the transgenic lines 1642:1661 Without, or with alkaline or hot water pretreatment, the saccharification efficiency of the transgenic lines was equal to that of the WT. 35860528 6 40 theme promoter 909:916 arg1 control 850:856 the control 846:856 the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B) 846:929 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 8 41 dep % 1218:1218 arg1 polysaccharides 1232:1246 more matrix polysaccharides 1220:1246 28% more matrix polysaccharides 1216:1246 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 3 42 theme lignified 453:461 arg1 walls 468:472 lignified cell walls 453:472 lignified cell walls of Arabidopsis 453:487 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 4 43 theme transgenic 597:606 arg1 plants 608:613 The resulting transgenic plants 583:613 The resulting transgenic plants 583:613 The resulting transgenic plants did not suffer from yield penalties and had an increased saccharification yield after alkaline pretreatment. 35860528 8 44 theme more 1220:1223 arg1 polysaccharides 1232:1246 more matrix polysaccharides 1220:1246 28% more matrix polysaccharides 1216:1246 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 3 45 theme cell 463:466 arg1 walls 468:472 lignified cell walls 453:472 lignified cell walls of Arabidopsis 453:487 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 6 46 theme SYNTHASE 895:902 arg1 ProCesA8-B 919:928 ProCesA8-B 919:928 ProCesA8-B 919:928 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 6 46 theme SYNTHASE 895:902 arg1 promoter 909:916 secondary cell wall CELLULOSE SYNTHASE A8-B promoter 865:916 the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B) 861:929 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 6 47 theme heterologous 799:810 arg1 expression 812:821 the heterologous expression 795:821 the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B) 795:929 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 6 48 theme wall 880:883 arg1 ProCesA8-B 919:928 ProCesA8-B 919:928 ProCesA8-B 919:928 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 6 48 theme wall 880:883 arg1 promoter 909:916 secondary cell wall CELLULOSE SYNTHASE A8-B promoter 865:916 the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B) 861:929 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 3 49 theme DIKETIDE-CoA 523:534 arg1 DCS 546:548 DCS 546:548 DCS 546:548 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 3 49 theme DIKETIDE-CoA 523:534 arg1 SYNTHASE 536:543 DIKETIDE-CoA SYNTHASE 523:543 DIKETIDE-CoA SYNTHASE (DCS) 523:549 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 6 50 theme secondary 865:873 arg1 ProCesA8-B 919:928 ProCesA8-B 919:928 ProCesA8-B 919:928 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 6 50 theme secondary 865:873 arg1 promoter 909:916 secondary cell wall CELLULOSE SYNTHASE A8-B promoter 865:916 the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B) 861:929 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 4 51 theme yield 635:639 arg1 penalties 641:649 yield penalties 635:649 yield penalties 635:649 The resulting transgenic plants did not suffer from yield penalties and had an increased saccharification yield after alkaline pretreatment. 35860528 12 52 with crops 2042:2046 arg1 walls 2058:2062 cell walls 2053:2062 cell walls 2053:2062 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 11 53 theme engineering 1819:1829 arg1 strategy 1831:1838 an engineering strategy 1816:1838 an engineering strategy for applications 1816:1855 These differences in (growth) phenotype illustrate that translational research in crops is essential to assess the value of an engineering strategy for applications. 35860528 9 54 theme syringyl/guaiacyl 1374:1390 arg1 S/G 1398:1400 S/G 1398:1400 S/G 1398:1400 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 54 theme syringyl/guaiacyl 1374:1390 arg1 unit 1392:1395 syringyl/guaiacyl unit 1374:1395 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 2 55 theme lignin 298:303 arg1 degradability 305:317 lignin degradability 298:317 lignin degradability 298:317 By engineering plants to partially replace traditional lignin monomers with alternative ones, lignin degradability and extractability can be enhanced. 35860528 1 56 theme lignin 196:201 arg1 presence 184:191 the presence 180:191 the presence of lignin 180:201 Lignocellulosic biomass is recalcitrant toward deconstruction into simple sugars mainly due to the presence of lignin. 35860528 12 57 theme cell 2053:2056 arg1 walls 2058:2062 cell walls 2053:2062 cell walls 2053:2062 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 8 58 dep wild-type 1145:1153 arg1 WT 1156:1157 WT 1156:1157 WT 1156:1157 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 9 59 theme increased 1413:1421 arg1 frequency 1423:1431 an increased frequency 1410:1431 an increased frequency of p-hydroxyphenyl (H) units 1410:1460 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 8 60 theme poplars 1184:1190 arg1 wood 1165:1168 the wood 1161:1168 the wood of transgenic poplars 1161:1190 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 11 61 from research 1762:1769 arg1 crops 1774:1778 crops 1774:1778 crops 1774:1778 These differences in (growth) phenotype illustrate that translational research in crops is essential to assess the value of an engineering strategy for applications. 35860528 8 62 theme matrix 1225:1230 arg1 polysaccharides 1232:1246 more matrix polysaccharides 1220:1246 28% more matrix polysaccharides 1216:1246 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 6 63 theme cell 995:998 arg1 walls 1000:1004 the lignified cell walls 981:1004 the lignified cell walls of poplar 981:1014 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 12 64 theme transgenic 2020:2029 arg1 crops 2042:2046 transgenic bio-energy crops 2020:2046 transgenic bio-energy crops with cell walls 2020:2062 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 10 65 theme water 1587:1591 arg1 pretreatment 1593:1604 alkaline or hot water pretreatment 1571:1604 pretreatment 1593:1604 Without, or with alkaline or hot water pretreatment, the saccharification efficiency of the transgenic lines was equal to that of the WT. 35860528 7 66 theme shoot-tip 1081:1089 arg1 necrosis 1091:1098 shoot-tip necrosis 1081:1098 shoot-tip necrosis 1081:1098 ProCesA8-B:DCS_CURS2 transgenic poplars, however, suffered from shoot-tip necrosis and yield penalties. 35860528 2 67 theme lignin 259:264 arg1 monomers 266:273 traditional lignin monomers 247:273 traditional lignin monomers 247:273 By engineering plants to partially replace traditional lignin monomers with alternative ones, lignin degradability and extractability can be enhanced. 35860528 12 68 theme strategy 1895:1902 arg1 fine-tuning 1866:1876 Further fine-tuning 1858:1876 Further fine-tuning of this research strategy 1858:1902 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 4 69 theme saccharification 672:687 arg1 yield 689:693 an increased saccharification yield 659:693 an increased saccharification yield 659:693 The resulting transgenic plants did not suffer from yield penalties and had an increased saccharification yield after alkaline pretreatment. 35860528 7 70 theme transgenic 1038:1047 arg1 poplars 1049:1055 ProCesA8-B:DCS_CURS2 transgenic poplars 1017:1055 ProCesA8-B:DCS_CURS2 transgenic poplars 1017:1055 ProCesA8-B:DCS_CURS2 transgenic poplars, however, suffered from shoot-tip necrosis and yield penalties. 35860528 1 71 theme simple 152:157 arg1 sugars 159:164 simple sugars 152:164 simple sugars mainly due to the presence of lignin 152:201 Lignocellulosic biomass is recalcitrant toward deconstruction into simple sugars mainly due to the presence of lignin. 35860528 12 72 theme bio-energy 2031:2040 arg1 crops 2042:2046 transgenic bio-energy crops 2020:2046 transgenic bio-energy crops with cell walls 2020:2062 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 9 73 theme decreased 1465:1473 arg1 frequency 1475:1483 a decreased frequency 1463:1483 a decreased frequency of p-hydroxybenzoates 1463:1505 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 3 74 theme SYNTHASE 536:543 arg1 expression 509:518 the heterologous expression 492:518 the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2) 492:580 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 8 75 theme altered 1285:1291 arg1 composition 1300:1310 a significantly altered lignin composition 1269:1310 a significantly altered lignin composition 1269:1310 Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. 35860528 12 76 dep e.g. 1905:1908 arg1 using 1914:1918 using 1914:1918 using more specific promoters 1914:1942 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 12 76 dep e.g. 1905:1908 arg1 translating 1950:1960 translating 1950:1960 translating this strategy to other crops such as maize 1950:2003 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 5 77 theme bio-energy 767:776 arg1 poplar 783:788 the bio-energy crop poplar 763:788 the bio-energy crop poplar 763:788 Here, we translated this strategy into the bio-energy crop poplar. 35860528 12 78 theme research 1886:1893 arg1 strategy 1895:1902 this research strategy 1881:1902 this research strategy 1881:1902 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 11 79 theme growth 1714:1719 arg1 phenotype 1722:1730 (growth) phenotype 1713:1730 (growth) phenotype 1713:1730 These differences in (growth) phenotype illustrate that translational research in crops is essential to assess the value of an engineering strategy for applications. 35860528 9 80 theme higher 1513:1518 arg1 fraction 1520:1527 a higher fraction 1511:1527 a higher fraction of phenylcoumaran units 1511:1551 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 3 81 theme monomer 383:389 arg1 curcumin 391:398 the alternative monomer curcumin 367:398 the alternative monomer curcumin 367:398 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 0 82 theme Curcumin 12:19 arg1 Biosynthesis 21:32 Engineering Curcumin Biosynthesis 0:32 Engineering Curcumin Biosynthesis in Poplar 0:42 Engineering Curcumin Biosynthesis in Poplar Affects Lignification and Biomass Yield. 35860528 12 83 theme Further 1858:1864 arg1 fine-tuning 1866:1876 Further fine-tuning 1858:1876 Further fine-tuning of this research strategy 1858:1902 Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield. 35860528 4 84 theme resulting 587:595 arg1 plants 608:613 The resulting transgenic plants 583:613 The resulting transgenic plants 583:613 The resulting transgenic plants did not suffer from yield penalties and had an increased saccharification yield after alkaline pretreatment. 35860528 9 85 theme units 1547:1551 arg1 frequency 1475:1483 a decreased frequency 1463:1483 a decreased frequency of p-hydroxybenzoates 1463:1505 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 85 theme units 1547:1551 arg1 frequency 1423:1431 an increased frequency 1410:1431 an increased frequency of p-hydroxyphenyl (H) units 1410:1460 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 85 theme units 1547:1551 arg1 fraction 1520:1527 a higher fraction 1511:1527 a higher fraction of phenylcoumaran units 1511:1551 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 85 theme units 1547:1551 arg1 ratio 1403:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 3 86 theme CURCUMIN 555:562 arg1 CURS2 575:579 CURS2 575:579 CURS2 575:579 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 3 86 theme CURCUMIN 555:562 arg1 SYNTHASE2 564:572 CURCUMIN SYNTHASE2 555:572 CURCUMIN SYNTHASE2 (CURS2) 555:580 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 9 87 theme ProCesA8-B 1332:1341 arg1 lignin 1353:1358 ProCesA8-B:DCS_CURS2 lignin 1332:1358 ProCesA8-B:DCS_CURS2 lignin 1332:1358 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 6 88 theme A8-B 904:907 arg1 ProCesA8-B 919:928 ProCesA8-B 919:928 ProCesA8-B 919:928 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 6 88 theme A8-B 904:907 arg1 promoter 909:916 secondary cell wall CELLULOSE SYNTHASE A8-B promoter 865:916 the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B) 861:929 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 10 89 theme saccharification 1611:1626 arg1 equal 1667:1671 equal 1667:1671 equal 1667:1671 Without, or with alkaline or hot water pretreatment, the saccharification efficiency of the transgenic lines was equal to that of the WT. 35860528 10 89 theme saccharification 1611:1626 arg1 efficiency 1628:1637 the saccharification efficiency 1607:1637 the saccharification efficiency of the transgenic lines 1607:1661 Without, or with alkaline or hot water pretreatment, the saccharification efficiency of the transgenic lines was equal to that of the WT. 35860528 3 90 theme heterologous 496:507 arg1 expression 509:518 the heterologous expression 492:518 the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2) 492:580 Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). 35860528 9 91 theme DCS_CURS2 1343:1351 arg1 lignin 1353:1358 ProCesA8-B:DCS_CURS2 lignin 1332:1358 ProCesA8-B:DCS_CURS2 lignin 1332:1358 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 6 92 theme CELLULOSE 885:893 arg1 ProCesA8-B 919:928 ProCesA8-B 919:928 ProCesA8-B 919:928 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 6 92 theme CELLULOSE 885:893 arg1 promoter 909:916 secondary cell wall CELLULOSE SYNTHASE A8-B promoter 865:916 the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B) 861:929 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 6 93 theme cell 875:878 arg1 ProCesA8-B 919:928 ProCesA8-B 919:928 ProCesA8-B 919:928 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 6 93 theme cell 875:878 arg1 promoter 909:916 secondary cell wall CELLULOSE SYNTHASE A8-B promoter 865:916 the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B) 861:929 Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. 35860528 9 94 contain had 1360:1362 arg2 ratio 1403:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 94 contain had 1360:1362 arg2 frequency 1423:1431 an increased frequency 1410:1431 an increased frequency of p-hydroxyphenyl (H) units 1410:1460 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 94 contain had 1360:1362 arg2 frequency 1475:1483 a decreased frequency 1463:1483 a decreased frequency of p-hydroxybenzoates 1463:1505 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 94 contain had 1360:1362 arg1 lignin 1353:1358 ProCesA8-B:DCS_CURS2 lignin 1332:1358 ProCesA8-B:DCS_CURS2 lignin 1332:1358 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 9 94 contain had 1360:1362 arg2 fraction 1520:1527 a higher fraction 1511:1527 a higher fraction of phenylcoumaran units 1511:1551 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 10 95 theme lines 1657:1661 arg1 equal 1667:1671 equal 1667:1671 equal 1667:1671 Without, or with alkaline or hot water pretreatment, the saccharification efficiency of the transgenic lines was equal to that of the WT. 35860528 10 95 theme lines 1657:1661 arg1 efficiency 1628:1637 the saccharification efficiency 1607:1637 the saccharification efficiency of the transgenic lines 1607:1661 Without, or with alkaline or hot water pretreatment, the saccharification efficiency of the transgenic lines was equal to that of the WT. 35860528 9 96 theme reduced 1366:1372 arg1 ratio 1403:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35860528 11 97 theme strategy 1831:1838 arg1 value 1807:1811 the value 1803:1811 the value of an engineering strategy for applications 1803:1855 These differences in (growth) phenotype illustrate that translational research in crops is essential to assess the value of an engineering strategy for applications. 35860528 9 98 theme unit 1392:1395 arg1 ratio 1403:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 a reduced syringyl/guaiacyl unit (S/G) ratio 1364:1407 More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. 35757248 0 0 theme medica 106:111 arg1 var 116:118 Citrus medica L. var 99:118 Citrus medica L. var 99:118 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 2 1 from var 202:204 arg1 polysaccharides 164:178 extract polysaccharides 156:178 extract polysaccharides from Citrus medica L. var 156:204 This study aimed to extract polysaccharides from Citrus medica L. var. 35757248 4 2 theme kDa 510:512 arg1 weight 489:494 an average molecular weight 468:494 an average molecular weight of 3.76 × 103 kDa 468:512 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 0 3 theme Citrus 99:104 arg1 var 116:118 Citrus medica L. var 99:118 Citrus medica L. var 99:118 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 0 4 from Characterization 11:26 arg1 var 116:118 Citrus medica L. var 99:118 Citrus medica L. var 99:118 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 4 5 theme average 471:477 arg1 weight 489:494 an average molecular weight 468:494 an average molecular weight of 3.76 × 103 kDa 468:512 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 4 6 theme DEAE-52 423:429 arg1 chromatography 448:461 Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography 365:461 chromatography 448:461 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 6 7 theme glucose 842:848 arg1 residues 850:857 glucose residues 842:857 glucose residues 842:857 Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. 35757248 10 8 theme natural 1393:1399 arg1 medicine 1401:1408 food or natural medicine 1385:1408 food or natural medicine 1385:1408 These results provide a basis for further use as one of the potential functions of food or natural medicine. 35757248 9 9 theme oxygen 1244:1249 arg1 species 1251:1257 reactive oxygen species 1235:1257 reactive oxygen species (ROS) 1235:1263 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 9 9 theme oxygen 1244:1249 arg1 ROS 1260:1262 ROS 1260:1262 ROS 1260:1262 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 7 10 theme radical 923:929 arg1 assays 942:947 ABTS radical scavenging assays 918:947 ABTS radical scavenging assays 918:947 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 3 11 theme citron 229:234 arg1 sarcodactylis 207:219 sarcodactylis 207:219 sarcodactylis (finger citron fruits) 207:242 sarcodactylis (finger citron fruits) and analyze their structures and potential bioactivities. 35757248 3 11 theme citron 229:234 arg1 fruits 236:241 finger citron fruits 222:241 finger citron fruits 222:241 sarcodactylis (finger citron fruits) and analyze their structures and potential bioactivities. 35757248 5 12 theme molar 626:630 arg1 ratio 632:636 a molar ratio 624:636 a molar ratio of 6.75:5.87:1.00 624:654 Monosaccharide composition analysis revealed that K-CLMP consisted of rhamnose, galactose, and glucose, with a molar ratio of 6.75:5.87:1.00. 35757248 7 13 theme crude 969:973 arg1 var 1007:1009 both crude polysaccharide Citrus medica L. var 964:1009 both crude polysaccharide Citrus medica L. var 964:1009 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 0 14 theme L. 113:114 arg1 var 116:118 Citrus medica L. var 99:118 Citrus medica L. var 99:118 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 6 15 theme rhamnose 883:890 arg1 O-4 876:878 O-4 876:878 O-4 of rhamnose 876:890 Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. 35757248 10 16 theme medicine 1401:1408 arg1 functions 1372:1380 the potential functions 1358:1380 the potential functions of food or natural medicine 1358:1408 These results provide a basis for further use as one of the potential functions of food or natural medicine. 35757248 4 17 theme column 441:446 arg1 chromatography 448:461 Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography 365:461 chromatography 448:461 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 5 18 theme Monosaccharide 515:528 arg1 analysis 542:549 Monosaccharide composition analysis 515:549 Monosaccharide composition analysis 515:549 Monosaccharide composition analysis revealed that K-CLMP consisted of rhamnose, galactose, and glucose, with a molar ratio of 6.75:5.87:1.00. 35757248 10 19 theme functions 1372:1380 arg1 functions 1372:1380 the potential functions 1358:1380 the potential functions of food or natural medicine 1358:1408 These results provide a basis for further use as one of the potential functions of food or natural medicine. 35757248 10 19 theme functions 1372:1380 arg1 one 1351:1353 one 1351:1353 one 1351:1353 These results provide a basis for further use as one of the potential functions of food or natural medicine. 35757248 5 20 theme 6.75:5.87:1.00 641:654 arg1 ratio 632:636 a molar ratio 624:636 a molar ratio of 6.75:5.87:1.00 624:654 Monosaccharide composition analysis revealed that K-CLMP consisted of rhamnose, galactose, and glucose, with a molar ratio of 6.75:5.87:1.00. 35757248 4 21 theme cellulose 431:439 arg1 chromatography 448:461 Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography 365:461 chromatography 448:461 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 4 22 theme new 304:306 arg1 polysaccharide 308:321 A new polysaccharide 302:321 A new polysaccharide named K-CMLP 302:334 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 9 23 from production 1173:1182 arg1 cells 1278:1282 RAW 264.7 cells 1268:1282 RAW 264.7 cells treated with LPS 1268:1299 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 2 24 theme extract 156:162 arg1 polysaccharides 164:178 extract polysaccharides 156:178 extract polysaccharides from Citrus medica L. var 156:204 This study aimed to extract polysaccharides from Citrus medica L. var. 35757248 4 25 theme -Sepharose 398:407 arg1 Flow 414:417 Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography 365:461 Flow 414:417 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 9 26 theme species 1251:1257 arg1 production 1173:1182 the production 1169:1182 the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS 1169:1299 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 7 27 theme scavenging 931:940 arg1 assays 942:947 ABTS radical scavenging assays 918:947 ABTS radical scavenging assays 918:947 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 0 28 from Activity 50:57 arg1 var 116:118 Citrus medica L. var 99:118 Citrus medica L. var 99:118 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 8 29 theme strong 1055:1060 arg1 properties 1086:1095 strong free-radical-scavenging properties 1055:1095 strong free-radical-scavenging properties 1055:1095 polysaccharide (CMLP) and K-CLMP exhibited strong free-radical-scavenging properties in a dose-dependent manner. 35757248 3 30 theme finger 222:227 arg1 sarcodactylis 207:219 sarcodactylis 207:219 sarcodactylis (finger citron fruits) 207:242 sarcodactylis (finger citron fruits) and analyze their structures and potential bioactivities. 35757248 3 30 theme finger 222:227 arg1 fruits 236:241 finger citron fruits 222:241 finger citron fruits 222:241 sarcodactylis (finger citron fruits) and analyze their structures and potential bioactivities. 35757248 0 31 theme Structural 0:9 arg1 Characterization 11:26 Structural Characterization 0:26 Structural Characterization 0:26 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 7 32 theme DPPH⋅ 908:912 arg1 results 897:903 The results 893:903 The results of DPPH⋅ and ABTS radical scavenging assays 893:947 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 4 33 theme molecular 479:487 arg1 weight 489:494 an average molecular weight 468:494 an average molecular weight of 3.76 × 103 kDa 468:512 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 0 34 theme Anti-inflammatory 32:48 arg1 Activity 50:57 Anti-inflammatory Activity 32:57 Anti-inflammatory Activity 32:57 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 10 35 theme food 1385:1388 arg1 medicine 1401:1408 food or natural medicine 1385:1408 food or natural medicine 1385:1408 These results provide a basis for further use as one of the potential functions of food or natural medicine. 35757248 4 36 theme Fast 409:412 arg1 Flow 414:417 Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography 365:461 Flow 414:417 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 9 37 theme cytokines 1204:1212 arg1 production 1173:1182 the production 1169:1182 the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS 1169:1299 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 9 38 theme pro-inflammatory 1187:1202 arg1 TNF-α 1224:1228 TNF-α 1224:1228 TNF-α 1224:1228 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 9 38 theme pro-inflammatory 1187:1202 arg1 IL-6 1215:1218 IL-6 1215:1218 IL-6 1215:1218 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 9 38 theme pro-inflammatory 1187:1202 arg1 cytokines 1204:1212 pro-inflammatory cytokines 1187:1212 pro-inflammatory cytokines (IL-6 and TNF-α) 1187:1229 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 7 39 theme Citrus 990:995 arg1 var 1007:1009 both crude polysaccharide Citrus medica L. var 964:1009 both crude polysaccharide Citrus medica L. var 964:1009 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 7 40 theme medica 997:1002 arg1 var 1007:1009 both crude polysaccharide Citrus medica L. var 964:1009 both crude polysaccharide Citrus medica L. var 964:1009 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 9 41 theme reactive 1235:1242 arg1 species 1251:1257 reactive oxygen species 1235:1257 reactive oxygen species (ROS) 1235:1263 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 9 41 theme reactive 1235:1242 arg1 ROS 1260:1262 ROS 1260:1262 ROS 1260:1262 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 7 42 theme assays 942:947 arg1 results 897:903 The results 893:903 The results of DPPH⋅ and ABTS radical scavenging assays 893:947 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 4 43 with Flow 414:417 arg1 weight 489:494 an average molecular weight 468:494 an average molecular weight of 3.76 × 103 kDa 468:512 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 5 44 theme composition 530:540 arg1 analysis 542:549 Monosaccharide composition analysis 515:549 Monosaccharide composition analysis 515:549 Monosaccharide composition analysis revealed that K-CLMP consisted of rhamnose, galactose, and glucose, with a molar ratio of 6.75:5.87:1.00. 35757248 3 45 theme potential 277:285 arg1 bioactivities 287:299 potential bioactivities 277:299 potential bioactivities 277:299 sarcodactylis (finger citron fruits) and analyze their structures and potential bioactivities. 35757248 2 46 theme L. 199:200 arg1 var 202:204 Citrus medica L. var 185:204 Citrus medica L. var 185:204 This study aimed to extract polysaccharides from Citrus medica L. var. 35757248 8 47 theme free-radical-scavenging 1062:1084 arg1 properties 1086:1095 strong free-radical-scavenging properties 1055:1095 strong free-radical-scavenging properties 1055:1095 polysaccharide (CMLP) and K-CLMP exhibited strong free-radical-scavenging properties in a dose-dependent manner. 35757248 6 48 theme magnetic 712:719 arg1 NMR 732:734 NMR 732:734 NMR 732:734 Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. 35757248 6 48 theme magnetic 712:719 arg1 resonance 721:729 two-dimensional nuclear magnetic resonance 688:729 two-dimensional nuclear magnetic resonance (NMR) 688:735 Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. 35757248 2 49 theme medica 192:197 arg1 var 202:204 Citrus medica L. var 185:204 Citrus medica L. var 185:204 This study aimed to extract polysaccharides from Citrus medica L. var. 35757248 4 50 theme Diethylaminoethylcellulose 365:390 arg1 -Sepharose 398:407 Diethylaminoethylcellulose (DEAE)-Sepharose 365:407 Diethylaminoethylcellulose (DEAE)-Sepharose 365:407 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 4 51 with chromatography 448:461 arg1 weight 489:494 an average molecular weight 468:494 an average molecular weight of 3.76 × 103 kDa 468:512 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 0 52 theme Galactorhamnan 64:77 arg1 Polysaccharide 79:92 a Galactorhamnan Polysaccharide 62:92 a Galactorhamnan Polysaccharide From Citrus medica L. var 62:118 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 2 53 theme Citrus 185:190 arg1 var 202:204 Citrus medica L. var 185:204 Citrus medica L. var 185:204 This study aimed to extract polysaccharides from Citrus medica L. var. 35757248 10 54 theme potential 1362:1370 arg1 functions 1372:1380 the potential functions 1358:1380 the potential functions of food or natural medicine 1358:1408 These results provide a basis for further use as one of the potential functions of food or natural medicine. 35757248 8 55 theme dose-dependent 1102:1115 arg1 manner 1117:1122 a dose-dependent manner 1100:1122 a dose-dependent manner 1100:1122 polysaccharide (CMLP) and K-CLMP exhibited strong free-radical-scavenging properties in a dose-dependent manner. 35757248 4 56 theme DEAE 393:396 arg1 -Sepharose 398:407 Diethylaminoethylcellulose (DEAE)-Sepharose 365:407 Diethylaminoethylcellulose (DEAE)-Sepharose 365:407 A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. 35757248 6 57 theme residues 850:857 arg1 number 832:837 a small number 824:837 a small number of glucose residues 824:857 Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. 35757248 6 58 theme nuclear 704:710 arg1 NMR 732:734 NMR 732:734 NMR 732:734 Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. 35757248 6 58 theme nuclear 704:710 arg1 resonance 721:729 two-dimensional nuclear magnetic resonance 688:729 two-dimensional nuclear magnetic resonance (NMR) 688:735 Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. 35757248 10 59 theme further 1336:1342 arg1 use 1344:1346 further use 1336:1346 further use as one of the potential functions of food or natural medicine 1336:1408 These results provide a basis for further use as one of the potential functions of food or natural medicine. 35757248 7 60 theme ABTS 918:921 arg1 assays 942:947 ABTS radical scavenging assays 918:947 ABTS radical scavenging assays 918:947 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 7 61 theme L. 1004:1005 arg1 var 1007:1009 both crude polysaccharide Citrus medica L. var 964:1009 both crude polysaccharide Citrus medica L. var 964:1009 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 6 62 theme two-dimensional 688:702 arg1 NMR 732:734 NMR 732:734 NMR 732:734 Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. 35757248 6 62 theme two-dimensional 688:702 arg1 resonance 721:729 two-dimensional nuclear magnetic resonance 688:729 two-dimensional nuclear magnetic resonance (NMR) 688:735 Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. 35757248 0 63 from var 116:118 arg1 Polysaccharide 79:92 a Galactorhamnan Polysaccharide 62:92 a Galactorhamnan Polysaccharide From Citrus medica L. var 62:118 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 0 63 from var 116:118 arg1 Characterization 11:26 Structural Characterization 0:26 Structural Characterization 0:26 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 0 63 from var 116:118 arg1 Activity 50:57 Anti-inflammatory Activity 32:57 Anti-inflammatory Activity 32:57 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 7 64 theme polysaccharide 975:988 arg1 var 1007:1009 both crude polysaccharide Citrus medica L. var 964:1009 both crude polysaccharide Citrus medica L. var 964:1009 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 7 65 dep indicated 949:957 arg1 var 1007:1009 both crude polysaccharide Citrus medica L. var 964:1009 both crude polysaccharide Citrus medica L. var 964:1009 The results of DPPH⋅ and ABTS radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. 35757248 9 66 theme RAW 1268:1270 arg1 cells 1278:1282 RAW 264.7 cells 1268:1282 RAW 264.7 cells treated with LPS 1268:1299 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 6 67 theme small 826:830 arg1 number 832:837 a small number 824:837 a small number of glucose residues 824:857 Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. 35757248 9 68 dep cytokines 1204:1212 arg1 TNF-α 1224:1228 TNF-α 1224:1228 TNF-α 1224:1228 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 9 68 dep cytokines 1204:1212 arg1 IL-6 1215:1218 IL-6 1215:1218 IL-6 1215:1218 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 9 68 dep cytokines 1204:1212 arg1 cytokines 1204:1212 pro-inflammatory cytokines 1187:1212 pro-inflammatory cytokines (IL-6 and TNF-α) 1187:1229 In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. 35757248 0 69 theme Polysaccharide 79:92 arg1 Characterization 11:26 Structural Characterization 0:26 Structural Characterization 0:26 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35757248 0 69 theme Polysaccharide 79:92 arg1 Activity 50:57 Anti-inflammatory Activity 32:57 Anti-inflammatory Activity 32:57 Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. 35660590 3 0 from samples 687:693 arg1 strains 674:680 21 strains 671:680 21 strains from samples 671:693 Hence, this study isolated 21 strains from samples in a large-scale MBR plant with routine CEB treatment. 35660590 1 1 theme anti-cleaning 340:352 arg1 properties 354:363 the strengthened anti-cleaning properties 323:363 the strengthened anti-cleaning properties of residual stubborn microbes 323:393 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 9 2 theme anti-cleaning 1646:1658 arg1 properties 1660:1669 the anti-cleaning properties 1642:1669 the anti-cleaning properties of biofilm 1642:1680 Both strategies aggravated biofouling and eventually enhanced the anti-cleaning properties of biofilm. 35660590 8 3 theme population 1509:1518 arg1 regrowth 1520:1527 quick population regrowth 1503:1527 quick population regrowth 1503:1527 Under such circumstances, stubborn strains would rather choose to be sensitive with surged QS level and quick population regrowth to maintain vitality under the oxidative stresses. 35660590 1 4 theme repeated 151:158 arg1 CEB 193:195 CEB 193:195 CEB 193:195 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 1 4 theme repeated 151:158 arg1 chemically-enhanced-backwashing 160:190 repeated chemically-enhanced-backwashing 151:190 repeated chemically-enhanced-backwashing (CEB) 151:196 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 3 5 theme CEB 735:737 arg1 treatment 739:747 routine CEB treatment 727:747 routine CEB treatment 727:747 Hence, this study isolated 21 strains from samples in a large-scale MBR plant with routine CEB treatment. 35660590 2 6 theme microbial 493:501 arg1 community 503:511 the whole post-CEB microbial community 474:511 the whole post-CEB microbial community 474:511 Although plenty of research has been done towards either the model strains or the whole post-CEB microbial community, little was known about the resisting behavior of practical stubborn strains when confronting oxidative stresses induced by NaClO. 35660590 1 7 theme chemically-enhanced-backwashing 160:190 arg1 performance 136:146 The declined performance 123:146 The declined performance of repeated chemically-enhanced-backwashing (CEB) 123:196 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 3 8 theme large-scale 700:710 arg1 plant 716:720 a large-scale MBR plant 698:720 a large-scale MBR plant 698:720 Hence, this study isolated 21 strains from samples in a large-scale MBR plant with routine CEB treatment. 35660590 7 9 theme survival 1351:1358 arg1 rate 1360:1363 consequent low survival rate 1336:1363 consequent low survival rate 1336:1363 However, sometimes EPS could not well resist the stimuli, with consequent low survival rate and high intracellular ROS level. 35660590 4 10 theme NaClO 903:907 arg1 stimuli 909:915 NaClO stimuli 903:915 NaClO stimuli 903:915 To unravel how they survive and affect membrane fouling, their anti-oxidation ability, fouling potential and quorum sensing (QS) effect before and after NaClO stimuli were evaluated. 35660590 5 11 theme weight 963:968 arg1 distribution 970:981 molecular weight distribution 953:981 molecular weight distribution 953:981 The composition and molecular weight distribution of extracellular polymeric substance (EPS) were also investigated to understand their roles during the anti-CEB process. 35660590 5 12 theme substance 1010:1018 arg1 distribution 970:981 molecular weight distribution 953:981 molecular weight distribution 953:981 The composition and molecular weight distribution of extracellular polymeric substance (EPS) were also investigated to understand their roles during the anti-CEB process. 35660590 5 12 theme substance 1010:1018 arg1 composition 937:947 composition 937:947 composition 937:947 The composition and molecular weight distribution of extracellular polymeric substance (EPS) were also investigated to understand their roles during the anti-CEB process. 35660590 0 13 theme EPS 86:88 arg1 shielding 90:98 EPS shielding 86:98 EPS shielding 86:98 Two strategies of stubborn biofouling strains surviving from NaClO membrane cleaning: EPS shielding and/or quorum sensing. 35660590 1 14 theme residual 368:375 arg1 microbes 386:393 residual stubborn microbes 368:393 residual stubborn microbes 368:393 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 2 15 theme oxidative 607:615 arg1 stresses 617:624 oxidative stresses 607:624 oxidative stresses induced by NaClO 607:641 Although plenty of research has been done towards either the model strains or the whole post-CEB microbial community, little was known about the resisting behavior of practical stubborn strains when confronting oxidative stresses induced by NaClO. 35660590 6 16 theme protective 1177:1186 arg1 shields 1188:1194 protective shields 1177:1194 protective shields 1177:1194 It was found that typical stubborn strains tended to secrete more EPS as protective shields, where polysaccharides (especially the ones >1 kDa) made major contribution. 35660590 0 17 theme quorum 107:112 arg1 sensing 114:120 quorum sensing 107:120 quorum sensing 107:120 Two strategies of stubborn biofouling strains surviving from NaClO membrane cleaning: EPS shielding and/or quorum sensing. 35660590 1 18 theme stubborn 377:384 arg1 microbes 386:393 residual stubborn microbes 368:393 residual stubborn microbes 368:393 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 6 19 theme major 1253:1257 arg1 contribution 1259:1270 major contribution 1253:1270 major contribution 1253:1270 It was found that typical stubborn strains tended to secrete more EPS as protective shields, where polysaccharides (especially the ones >1 kDa) made major contribution. 35660590 2 20 theme research 415:422 arg1 plenty 405:410 plenty 405:410 plenty of research 405:422 Although plenty of research has been done towards either the model strains or the whole post-CEB microbial community, little was known about the resisting behavior of practical stubborn strains when confronting oxidative stresses induced by NaClO. 35660590 1 21 theme microbes 386:393 arg1 properties 354:363 the strengthened anti-cleaning properties 323:363 the strengthened anti-cleaning properties of residual stubborn microbes 323:393 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 0 22 theme strains 38:44 arg1 strategies 4:13 Two strategies 0:13 Two strategies of stubborn biofouling strains surviving from NaClO membrane cleaning: EPS shielding and/or quorum sensing. 0:121 Two strategies of stubborn biofouling strains surviving from NaClO membrane cleaning: EPS shielding and/or quorum sensing. 35660590 8 23 theme quick 1503:1507 arg1 regrowth 1520:1527 quick population regrowth 1503:1527 quick population regrowth 1503:1527 Under such circumstances, stubborn strains would rather choose to be sensitive with surged QS level and quick population regrowth to maintain vitality under the oxidative stresses. 35660590 5 24 theme extracellular 986:998 arg1 EPS 1021:1023 EPS 1021:1023 EPS 1021:1023 The composition and molecular weight distribution of extracellular polymeric substance (EPS) were also investigated to understand their roles during the anti-CEB process. 35660590 5 24 theme extracellular 986:998 arg1 substance 1010:1018 extracellular polymeric substance 986:1018 extracellular polymeric substance (EPS) 986:1024 The composition and molecular weight distribution of extracellular polymeric substance (EPS) were also investigated to understand their roles during the anti-CEB process. 35660590 2 25 theme whole 478:482 arg1 community 503:511 the whole post-CEB microbial community 474:511 the whole post-CEB microbial community 474:511 Although plenty of research has been done towards either the model strains or the whole post-CEB microbial community, little was known about the resisting behavior of practical stubborn strains when confronting oxidative stresses induced by NaClO. 35660590 3 26 theme routine 727:733 arg1 treatment 739:747 routine CEB treatment 727:747 routine CEB treatment 727:747 Hence, this study isolated 21 strains from samples in a large-scale MBR plant with routine CEB treatment. 35660590 6 27 theme more 1165:1168 arg1 EPS 1170:1172 more EPS 1165:1172 more EPS 1165:1172 It was found that typical stubborn strains tended to secrete more EPS as protective shields, where polysaccharides (especially the ones >1 kDa) made major contribution. 35660590 4 28 dep fouling 798:804 arg1 effect 879:884 effect 879:884 effect 879:884 To unravel how they survive and affect membrane fouling, their anti-oxidation ability, fouling potential and quorum sensing (QS) effect before and after NaClO stimuli were evaluated. 35660590 2 29 theme model 457:461 arg1 strains 463:469 the model strains 453:469 the model strains 453:469 Although plenty of research has been done towards either the model strains or the whole post-CEB microbial community, little was known about the resisting behavior of practical stubborn strains when confronting oxidative stresses induced by NaClO. 35660590 4 30 theme quorum 859:864 arg1 QS 875:876 QS 875:876 QS 875:876 To unravel how they survive and affect membrane fouling, their anti-oxidation ability, fouling potential and quorum sensing (QS) effect before and after NaClO stimuli were evaluated. 35660590 4 30 theme quorum 859:864 arg1 sensing 866:872 quorum sensing 859:872 quorum sensing (QS) 859:877 To unravel how they survive and affect membrane fouling, their anti-oxidation ability, fouling potential and quorum sensing (QS) effect before and after NaClO stimuli were evaluated. 35660590 0 31 theme stubborn 18:25 arg1 strains 38:44 stubborn biofouling strains 18:44 stubborn biofouling strains surviving from NaClO membrane cleaning 18:83 Two strategies of stubborn biofouling strains surviving from NaClO membrane cleaning: EPS shielding and/or quorum sensing. 35660590 2 32 theme practical 563:571 arg1 strains 582:588 practical stubborn strains 563:588 practical stubborn strains 563:588 Although plenty of research has been done towards either the model strains or the whole post-CEB microbial community, little was known about the resisting behavior of practical stubborn strains when confronting oxidative stresses induced by NaClO. 35660590 5 33 dep composition 937:947 arg1 The 933:935 The 933:935 The 933:935 The composition and molecular weight distribution of extracellular polymeric substance (EPS) were also investigated to understand their roles during the anti-CEB process. 35660590 5 34 theme molecular 953:961 arg1 distribution 970:981 molecular weight distribution 953:981 molecular weight distribution 953:981 The composition and molecular weight distribution of extracellular polymeric substance (EPS) were also investigated to understand their roles during the anti-CEB process. 35660590 7 35 theme low 1347:1349 arg1 rate 1360:1363 consequent low survival rate 1336:1363 consequent low survival rate 1336:1363 However, sometimes EPS could not well resist the stimuli, with consequent low survival rate and high intracellular ROS level. 35660590 2 36 theme post-CEB 484:491 arg1 community 503:511 the whole post-CEB microbial community 474:511 the whole post-CEB microbial community 474:511 Although plenty of research has been done towards either the model strains or the whole post-CEB microbial community, little was known about the resisting behavior of practical stubborn strains when confronting oxidative stresses induced by NaClO. 35660590 8 37 theme stubborn 1425:1432 arg1 strains 1434:1440 stubborn strains 1425:1440 stubborn strains 1425:1440 Under such circumstances, stubborn strains would rather choose to be sensitive with surged QS level and quick population regrowth to maintain vitality under the oxidative stresses. 35660590 1 38 theme sustainable 221:231 arg1 operation 233:241 the sustainable operation 217:241 the sustainable operation of membrane bioreactor (MBR) in long-term 217:283 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 0 39 theme biofouling 27:36 arg1 strains 38:44 stubborn biofouling strains 18:44 stubborn biofouling strains surviving from NaClO membrane cleaning 18:83 Two strategies of stubborn biofouling strains surviving from NaClO membrane cleaning: EPS shielding and/or quorum sensing. 35660590 8 40 theme oxidative 1560:1568 arg1 stresses 1570:1577 the oxidative stresses 1556:1577 the oxidative stresses 1556:1577 Under such circumstances, stubborn strains would rather choose to be sensitive with surged QS level and quick population regrowth to maintain vitality under the oxidative stresses. 35660590 2 41 theme resisting 541:549 arg1 behavior 551:558 the resisting behavior 537:558 the resisting behavior of practical stubborn strains 537:588 Although plenty of research has been done towards either the model strains or the whole post-CEB microbial community, little was known about the resisting behavior of practical stubborn strains when confronting oxidative stresses induced by NaClO. 35660590 5 42 theme anti-CEB 1086:1093 arg1 process 1095:1101 the anti-CEB process 1082:1101 the anti-CEB process 1082:1101 The composition and molecular weight distribution of extracellular polymeric substance (EPS) were also investigated to understand their roles during the anti-CEB process. 35660590 4 43 theme anti-oxidation 813:826 arg1 ability 828:834 their anti-oxidation ability 807:834 their anti-oxidation ability 807:834 To unravel how they survive and affect membrane fouling, their anti-oxidation ability, fouling potential and quorum sensing (QS) effect before and after NaClO stimuli were evaluated. 35660590 4 44 theme fouling 837:843 arg1 potential 845:853 fouling potential 837:853 fouling potential 837:853 To unravel how they survive and affect membrane fouling, their anti-oxidation ability, fouling potential and quorum sensing (QS) effect before and after NaClO stimuli were evaluated. 35660590 1 45 from operation 233:241 arg1 long-term 275:283 long-term 275:283 long-term 275:283 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 8 46 theme QS 1490:1491 arg1 level 1493:1497 QS level 1490:1497 QS level 1490:1497 Under such circumstances, stubborn strains would rather choose to be sensitive with surged QS level and quick population regrowth to maintain vitality under the oxidative stresses. 35660590 3 47 theme MBR 712:714 arg1 plant 716:720 a large-scale MBR plant 698:720 a large-scale MBR plant 698:720 Hence, this study isolated 21 strains from samples in a large-scale MBR plant with routine CEB treatment. 35660590 9 48 theme biofilm 1674:1680 arg1 properties 1660:1669 the anti-cleaning properties 1642:1669 the anti-cleaning properties of biofilm 1642:1680 Both strategies aggravated biofouling and eventually enhanced the anti-cleaning properties of biofilm. 35660590 6 49 theme stubborn 1130:1137 arg1 strains 1139:1145 typical stubborn strains 1122:1145 typical stubborn strains 1122:1145 It was found that typical stubborn strains tended to secrete more EPS as protective shields, where polysaccharides (especially the ones >1 kDa) made major contribution. 35660590 8 50 theme such 1405:1408 arg1 circumstances 1410:1422 such circumstances 1405:1422 such circumstances 1405:1422 Under such circumstances, stubborn strains would rather choose to be sensitive with surged QS level and quick population regrowth to maintain vitality under the oxidative stresses. 35660590 2 51 theme strains 582:588 arg1 behavior 551:558 the resisting behavior 537:558 the resisting behavior of practical stubborn strains 537:588 Although plenty of research has been done towards either the model strains or the whole post-CEB microbial community, little was known about the resisting behavior of practical stubborn strains when confronting oxidative stresses induced by NaClO. 35660590 7 52 theme consequent 1336:1345 arg1 rate 1360:1363 consequent low survival rate 1336:1363 consequent low survival rate 1336:1363 However, sometimes EPS could not well resist the stimuli, with consequent low survival rate and high intracellular ROS level. 35660590 5 53 theme polymeric 1000:1008 arg1 EPS 1021:1023 EPS 1021:1023 EPS 1021:1023 The composition and molecular weight distribution of extracellular polymeric substance (EPS) were also investigated to understand their roles during the anti-CEB process. 35660590 5 53 theme polymeric 1000:1008 arg1 substance 1010:1018 extracellular polymeric substance 986:1018 extracellular polymeric substance (EPS) 986:1024 The composition and molecular weight distribution of extracellular polymeric substance (EPS) were also investigated to understand their roles during the anti-CEB process. 35660590 6 54 theme ones 1235:1238 arg1 polysaccharides 1203:1217 polysaccharides 1203:1217 polysaccharides (especially the ones >1 kDa) 1203:1246 It was found that typical stubborn strains tended to secrete more EPS as protective shields, where polysaccharides (especially the ones >1 kDa) made major contribution. 35660590 6 54 theme ones 1235:1238 arg1 kDa 1243:1245 especially the ones >1 kDa 1220:1245 especially the ones >1 kDa 1220:1245 It was found that typical stubborn strains tended to secrete more EPS as protective shields, where polysaccharides (especially the ones >1 kDa) made major contribution. 35660590 6 55 theme typical 1122:1128 arg1 strains 1139:1145 typical stubborn strains 1122:1145 typical stubborn strains 1122:1145 It was found that typical stubborn strains tended to secrete more EPS as protective shields, where polysaccharides (especially the ones >1 kDa) made major contribution. 35660590 7 56 theme intracellular 1374:1386 arg1 level 1392:1396 high intracellular ROS level 1369:1396 high intracellular ROS level 1369:1396 However, sometimes EPS could not well resist the stimuli, with consequent low survival rate and high intracellular ROS level. 35660590 7 57 theme ROS 1388:1390 arg1 level 1392:1396 high intracellular ROS level 1369:1396 high intracellular ROS level 1369:1396 However, sometimes EPS could not well resist the stimuli, with consequent low survival rate and high intracellular ROS level. 35660590 2 58 theme stubborn 573:580 arg1 strains 582:588 practical stubborn strains 563:588 practical stubborn strains 563:588 Although plenty of research has been done towards either the model strains or the whole post-CEB microbial community, little was known about the resisting behavior of practical stubborn strains when confronting oxidative stresses induced by NaClO. 35660590 4 59 theme membrane 789:796 arg1 fouling 798:804 membrane fouling 789:804 membrane fouling 789:804 To unravel how they survive and affect membrane fouling, their anti-oxidation ability, fouling potential and quorum sensing (QS) effect before and after NaClO stimuli were evaluated. 35660590 1 60 theme declined 127:134 arg1 performance 136:146 The declined performance 123:146 The declined performance of repeated chemically-enhanced-backwashing (CEB) 123:196 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 1 61 theme membrane 246:253 arg1 bioreactor 255:264 membrane bioreactor 246:264 membrane bioreactor (MBR) 246:270 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 1 61 theme membrane 246:253 arg1 MBR 267:269 MBR 267:269 MBR 267:269 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 0 62 theme membrane 67:74 arg1 cleaning 76:83 NaClO membrane cleaning 61:83 NaClO membrane cleaning 61:83 Two strategies of stubborn biofouling strains surviving from NaClO membrane cleaning: EPS shielding and/or quorum sensing. 35660590 0 63 dep strategies 4:13 arg1 shielding 90:98 EPS shielding 86:98 EPS shielding 86:98 Two strategies of stubborn biofouling strains surviving from NaClO membrane cleaning: EPS shielding and/or quorum sensing. 35660590 0 63 dep strategies 4:13 arg1 sensing 114:120 quorum sensing 107:120 quorum sensing 107:120 Two strategies of stubborn biofouling strains surviving from NaClO membrane cleaning: EPS shielding and/or quorum sensing. 35660590 1 64 theme bioreactor 255:264 arg1 operation 233:241 the sustainable operation 217:241 the sustainable operation of membrane bioreactor (MBR) in long-term 217:283 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 0 65 theme NaClO 61:65 arg1 cleaning 76:83 NaClO membrane cleaning 61:83 NaClO membrane cleaning 61:83 Two strategies of stubborn biofouling strains surviving from NaClO membrane cleaning: EPS shielding and/or quorum sensing. 35660590 1 66 theme strengthened 327:338 arg1 properties 354:363 the strengthened anti-cleaning properties 323:363 the strengthened anti-cleaning properties of residual stubborn microbes 323:393 The declined performance of repeated chemically-enhanced-backwashing (CEB) seriously hampered the sustainable operation of membrane bioreactor (MBR) in long-term, and could be partially attributed to the strengthened anti-cleaning properties of residual stubborn microbes. 35660590 7 67 theme high 1369:1372 arg1 level 1392:1396 high intracellular ROS level 1369:1396 high intracellular ROS level 1369:1396 However, sometimes EPS could not well resist the stimuli, with consequent low survival rate and high intracellular ROS level. 35360689 4 0 theme structure 796:804 arg1 characterization 806:821 the structure characterization 792:821 the structure characterization 792:821 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 10 1 theme large 1757:1761 arg1 amount 1763:1768 a large amount 1755:1768 a large amount of cellulose 1755:1781 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 10 1 theme large 1757:1761 arg1 cellulose 1773:1781 cellulose 1773:1781 cellulose 1773:1781 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 9 2 theme Ganoderma 1531:1539 arg1 lucidum 1541:1547 Ganoderma lucidum 1531:1547 Ganoderma lucidum 1531:1547 The yield of four kinds of IDF from high to low came from Ganoderma lucidum, Hericium erinaceus, Lentinus edodes, and Grifola frondosa. 35360689 6 3 theme residues 1139:1146 arg1 kinds 1117:1121 the four kinds 1108:1121 the four kinds of edible fungi residues 1108:1146 The results showed that IDF in the four kinds of edible fungi residues was similar in composition but different in texture. 35360689 10 4 contain contained 1745:1753 arg1 them 1740:1743 them 1740:1743 them 1740:1743 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 10 4 contain contained 1745:1753 arg2 cellulose 1773:1781 cellulose 1773:1781 cellulose 1773:1781 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 10 4 contain contained 1745:1753 arg1 all 1733:1735 all 1733:1735 all 1733:1735 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 10 4 contain contained 1745:1753 arg2 amount 1763:1768 a large amount 1755:1768 a large amount of cellulose 1755:1781 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 11 5 theme holding 1863:1869 arg1 capacity 1871:1878 certain water holding capacity 1849:1878 certain water holding capacity 1849:1878 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 4 6 theme food 777:780 arg1 industry 782:789 the food industry 773:789 the food industry 773:789 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 11 7 theme certain 1849:1855 arg1 capacity 1871:1878 certain water holding capacity 1849:1878 certain water holding capacity 1849:1878 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 1 8 theme rapid 158:162 arg1 development 164:174 the rapid development 154:174 the rapid development of the edible fungi industry in the world 154:216 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 9 9 theme Lentinus 1570:1577 arg1 edodes 1579:1584 Lentinus edodes 1570:1584 Lentinus edodes 1570:1584 The yield of four kinds of IDF from high to low came from Ganoderma lucidum, Hericium erinaceus, Lentinus edodes, and Grifola frondosa. 35360689 8 10 contain have 1441:1444 arg1 frondosa 1432:1439 Grifola frondosa 1424:1439 Grifola frondosa 1424:1439 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 8 10 contain have 1441:1444 arg1 lucidum 1412:1418 Ganoderma lucidum 1402:1418 Ganoderma lucidum 1402:1418 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 8 10 contain have 1441:1444 arg2 texture 1464:1470 a relatively hard texture 1446:1470 a relatively hard texture 1446:1470 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 11 11 theme binding 1887:1893 arg1 capacity 1895:1902 water binding capacity 1881:1902 water binding capacity 1881:1902 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 2 12 theme dietary 523:529 arg1 IDF 538:540 IDF 538:540 IDF 538:540 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 12 theme dietary 523:529 arg1 fiber 531:535 water-insoluble dietary fiber 507:535 water-insoluble dietary fiber (IDF) 507:541 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 1 13 theme sustainable 341:351 arg1 development 353:363 the industry's sustainable development 326:363 the industry's sustainable development 326:363 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 10 14 theme X-ray 1641:1645 arg1 spectra 1665:1671 X-ray diffraction (XRD) spectra 1641:1671 X-ray diffraction (XRD) spectra 1641:1671 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 1 15 theme edible 183:188 arg1 industry 196:203 the edible fungi industry 179:203 the edible fungi industry 179:203 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 9 16 theme Grifola 1591:1597 arg1 frondosa 1599:1606 Grifola frondosa 1591:1606 Grifola frondosa 1591:1606 The yield of four kinds of IDF from high to low came from Ganoderma lucidum, Hericium erinaceus, Lentinus edodes, and Grifola frondosa. 35360689 8 17 theme granular 1351:1358 arg1 texture 1360:1366 obvious granular texture 1343:1366 obvious granular texture 1343:1366 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 4 18 from influence 860:868 arg1 intake 895:900 dietary energy intake 880:900 dietary energy intake 880:900 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 1 19 theme industry 196:203 arg1 development 164:174 the rapid development 154:174 the rapid development of the edible fungi industry in the world 154:216 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 7 20 theme fungi 1282:1286 arg1 kinds 1266:1270 four kinds 1261:1270 four kinds of edible fungi 1261:1286 Cellulose and hemicellulose are the main IDF extracted from four kinds of edible fungi. 35360689 0 21 theme Energy 134:139 arg1 Intake 141:146 Energy Intake 134:146 Energy Intake 134:146 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 8 22 theme Lentinus 1379:1386 arg1 edodes 1388:1393 Lentinus edodes 1379:1393 Lentinus edodes 1379:1393 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 11 23 theme holding 1913:1919 arg1 capacity 1921:1928 oil holding capacity 1909:1928 oil holding capacity 1909:1928 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 0 24 from Properties 101:110 arg1 Intake 141:146 Energy Intake 134:146 Energy Intake 134:146 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 6 25 theme edible 1126:1131 arg1 residues 1139:1146 edible fungi residues 1126:1146 edible fungi residues 1126:1146 The results showed that IDF in the four kinds of edible fungi residues was similar in composition but different in texture. 35360689 12 26 theme In-vitro 1931:1938 arg1 experiments 1950:1960 In-vitro digestion experiments 1931:1960 In-vitro digestion experiments 1931:1960 In-vitro digestion experiments showed that the four IDFs could inhibit the digestion of starch and fat to a certain extent. 35360689 4 27 from properties 840:849 arg1 intake 895:900 dietary energy intake 880:900 dietary energy intake 880:900 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 1 28 from development 164:174 arg1 world 212:216 the world 208:216 the world 208:216 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 11 29 theme Physical 1784:1791 arg1 analysis 1806:1813 Physical and chemical analysis 1784:1813 Physical and chemical analysis 1784:1813 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 0 30 theme Industry 58:65 arg1 By-Products 30:40 By-Products 30:40 By-Products of Edible Fungi Industry 30:65 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 3 31 theme extracted 560:568 arg1 waste 622:626 solid waste 616:626 solid waste 616:626 At present, the extracted residue is generally treated as fertilizer or solid waste, which not only pollutes the environment, but wastes resources too. 35360689 3 31 theme extracted 560:568 arg1 fertilizer 602:611 fertilizer 602:611 fertilizer 602:611 At present, the extracted residue is generally treated as fertilizer or solid waste, which not only pollutes the environment, but wastes resources too. 35360689 3 31 theme extracted 560:568 arg1 residue 570:576 the extracted residue 556:576 the extracted residue 556:576 At present, the extracted residue is generally treated as fertilizer or solid waste, which not only pollutes the environment, but wastes resources too. 35360689 2 32 theme large 456:460 arg1 proportion 462:471 a large proportion 454:471 a large proportion 454:471 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 8 33 theme Ganoderma 1402:1410 arg1 lucidum 1412:1418 Ganoderma lucidum 1402:1418 Ganoderma lucidum 1402:1418 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 11 34 theme water 1881:1885 arg1 capacity 1895:1902 water binding capacity 1881:1902 water binding capacity 1881:1902 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 0 35 theme Basic 68:72 arg1 Structure 74:82 Basic Structure 68:82 Basic Structure 68:82 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 1 36 theme urgent 307:312 arg1 problem 314:320 an urgent problem 304:320 an urgent problem for the industry's sustainable development 304:363 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 4 37 theme dietary 880:886 arg1 intake 895:900 dietary energy intake 880:900 dietary energy intake 880:900 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 10 38 dep Fourier 1609:1615 arg1 transform 1617:1625 transform 1617:1625 transform IR (FTIR) 1617:1635 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 13 39 theme physiological 2247:2259 arg1 functions 2261:2269 physiological functions 2247:2269 physiological functions 2247:2269 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 10 40 dep IR 1627:1628 arg1 FTIR 1631:1634 FTIR 1631:1634 FTIR 1631:1634 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 5 41 theme Analytical 1042:1051 arg1 method 1069:1074 Official Analytical Chemists (AOAC) method 1033:1074 Official Analytical Chemists (AOAC) method 1033:1074 The IDF from the residues of polysaccharides extracted from four edible fungi was extracted using the Association of Official Analytical Chemists (AOAC) method. 35360689 0 42 from By-Products 30:40 arg1 Fibers 18:23 Insoluble Dietary Fibers 0:23 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 0:147 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 12 43 theme certain 2039:2045 arg1 extent 2047:2052 a certain extent 2037:2052 a certain extent 2037:2052 In-vitro digestion experiments showed that the four IDFs could inhibit the digestion of starch and fat to a certain extent. 35360689 0 44 theme Insoluble 0:8 arg1 Fibers 18:23 Insoluble Dietary Fibers 0:23 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 0:147 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 8 45 theme hard 1459:1462 arg1 texture 1464:1470 a relatively hard texture 1446:1470 a relatively hard texture 1446:1470 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 4 46 theme potential 748:756 arg1 utilization 758:768 their potential utilization 742:768 their potential utilization in the food industry 742:789 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 2 47 theme edible 387:392 arg1 fungi 394:398 edible fungi 387:398 edible fungi 387:398 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 13 48 theme edible 2070:2075 arg1 fungi 2077:2081 edible fungi 2070:2081 edible fungi 2070:2081 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 9 49 theme kinds 1491:1495 arg1 yield 1477:1481 The yield 1473:1481 The yield of four kinds of IDF from high to low 1473:1519 The yield of four kinds of IDF from high to low came from Ganoderma lucidum, Hericium erinaceus, Lentinus edodes, and Grifola frondosa. 35360689 8 50 theme Hericium 1301:1308 arg1 erinaceus 1310:1318 Hericium erinaceus 1301:1318 Hericium erinaceus 1301:1318 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 8 50 theme Hericium 1301:1308 arg1 softest 1327:1333 the softest 1323:1333 the softest without obvious granular texture 1323:1366 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 1 51 theme edible 268:273 arg1 by-products 281:291 edible fungi by-products 268:291 edible fungi by-products 268:291 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 5 52 theme polysaccharides 945:959 arg1 polysaccharides 945:959 polysaccharides 945:959 polysaccharides extracted from four edible fungi 945:992 The IDF from the residues of polysaccharides extracted from four edible fungi was extracted using the Association of Official Analytical Chemists (AOAC) method. 35360689 5 52 theme polysaccharides 945:959 arg1 residues 933:940 the residues 929:940 the residues of polysaccharides extracted from four edible fungi 929:992 The IDF from the residues of polysaccharides extracted from four edible fungi was extracted using the Association of Official Analytical Chemists (AOAC) method. 35360689 10 53 theme similar 1703:1709 arg1 groups 1722:1727 similar functional groups 1703:1727 similar functional groups 1703:1727 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 0 54 theme Edible 45:50 arg1 Industry 58:65 Edible Fungi Industry 45:65 Edible Fungi Industry 45:65 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 1 55 theme by-products 281:291 arg1 utilization 253:263 the resource utilization 240:263 the resource utilization of edible fungi by-products 240:291 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 13 56 theme due 2203:2205 arg1 materials 2193:2201 functional food materials 2177:2201 functional food materials due to their physicochemical properties and physiological functions 2177:2269 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 9 57 theme IDF 1500:1502 arg1 kinds 1491:1495 four kinds 1486:1495 four kinds of IDF 1486:1502 The yield of four kinds of IDF from high to low came from Ganoderma lucidum, Hericium erinaceus, Lentinus edodes, and Grifola frondosa. 35360689 6 58 from texture 1192:1198 arg1 different 1179:1187 different 1179:1187 different 1179:1187 The results showed that IDF in the four kinds of edible fungi residues was similar in composition but different in texture. 35360689 0 59 dep Fibers 18:23 arg1 Effects 123:129 Their Effects 117:129 Their Effects on Energy Intake 117:146 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 0 59 dep Fibers 18:23 arg1 Structure 74:82 Basic Structure 68:82 Basic Structure 68:82 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 0 59 dep Fibers 18:23 arg1 Properties 101:110 Physicochemical Properties 85:110 Physicochemical Properties 85:110 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 0 60 from Effects 123:129 arg1 Intake 141:146 Energy Intake 134:146 Energy Intake 134:146 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 3 61 theme solid 616:620 arg1 residue 570:576 the extracted residue 556:576 the extracted residue 556:576 At present, the extracted residue is generally treated as fertilizer or solid waste, which not only pollutes the environment, but wastes resources too. 35360689 3 61 theme solid 616:620 arg1 waste 622:626 solid waste 616:626 solid waste 616:626 At present, the extracted residue is generally treated as fertilizer or solid waste, which not only pollutes the environment, but wastes resources too. 35360689 8 62 theme obvious 1343:1349 arg1 texture 1360:1366 obvious granular texture 1343:1366 obvious granular texture 1343:1366 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 2 63 contain contains 480:487 arg1 proportion 462:471 a large proportion 454:471 a large proportion 454:471 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 63 contain contains 480:487 arg2 amount 497:502 a large amount 489:502 a large amount of water-insoluble dietary fiber (IDF) 489:541 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 63 contain contains 480:487 arg2 IDF 538:540 IDF 538:540 IDF 538:540 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 63 contain contains 480:487 arg2 fiber 531:535 water-insoluble dietary fiber 507:535 water-insoluble dietary fiber (IDF) 507:541 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 13 64 theme food 2188:2191 arg1 materials 2193:2201 functional food materials 2177:2201 functional food materials due to their physicochemical properties and physiological functions 2177:2269 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 6 65 from composition 1163:1173 arg1 similar 1152:1158 similar 1152:1158 similar 1152:1158 The results showed that IDF in the four kinds of edible fungi residues was similar in composition but different in texture. 35360689 5 66 theme AOAC 1063:1066 arg1 method 1069:1074 Official Analytical Chemists (AOAC) method 1033:1074 Official Analytical Chemists (AOAC) method 1033:1074 The IDF from the residues of polysaccharides extracted from four edible fungi was extracted using the Association of Official Analytical Chemists (AOAC) method. 35360689 11 67 theme water 1857:1861 arg1 capacity 1871:1878 certain water holding capacity 1849:1878 certain water holding capacity 1849:1878 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 6 68 from different 1179:1187 arg1 texture 1192:1198 texture 1192:1198 texture 1192:1198 The results showed that IDF in the four kinds of edible fungi residues was similar in composition but different in texture. 35360689 11 69 contain had 1845:1847 arg2 capacity 1895:1902 water binding capacity 1881:1902 water binding capacity 1881:1902 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 11 69 contain had 1845:1847 arg2 capacity 1921:1928 oil holding capacity 1909:1928 oil holding capacity 1909:1928 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 11 69 contain had 1845:1847 arg2 capacity 1871:1878 certain water holding capacity 1849:1878 certain water holding capacity 1849:1878 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 11 69 contain had 1845:1847 arg1 IDFs 1840:1843 all the four IDFs 1827:1843 all the four IDFs 1827:1843 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 9 70 theme Hericium 1550:1557 arg1 erinaceus 1559:1567 Hericium erinaceus 1550:1567 Hericium erinaceus 1550:1567 The yield of four kinds of IDF from high to low came from Ganoderma lucidum, Hericium erinaceus, Lentinus edodes, and Grifola frondosa. 35360689 5 71 from residues 933:940 arg1 IDF 920:922 The IDF 916:922 The IDF from the residues of polysaccharides extracted from four edible fungi 916:992 The IDF from the residues of polysaccharides extracted from four edible fungi was extracted using the Association of Official Analytical Chemists (AOAC) method. 35360689 10 72 theme cellulose 1773:1781 arg1 amount 1763:1768 a large amount 1755:1768 a large amount of cellulose 1755:1781 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 10 72 theme cellulose 1773:1781 arg1 cellulose 1773:1781 cellulose 1773:1781 cellulose 1773:1781 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 10 73 theme XRD 1660:1662 arg1 spectra 1665:1671 X-ray diffraction (XRD) spectra 1641:1671 X-ray diffraction (XRD) spectra 1641:1671 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 10 74 theme diffraction 1647:1657 arg1 spectra 1665:1671 X-ray diffraction (XRD) spectra 1641:1671 X-ray diffraction (XRD) spectra 1641:1671 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 13 75 theme IDFs 2125:2128 arg1 recovery 2113:2120 the recovery 2109:2120 the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions 2109:2269 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 2 76 theme water-insoluble 507:521 arg1 IDF 538:540 IDF 538:540 IDF 538:540 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 76 theme water-insoluble 507:521 arg1 fiber 531:535 water-insoluble dietary fiber 507:535 water-insoluble dietary fiber (IDF) 507:541 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 0 77 from Structure 74:82 arg1 Intake 141:146 Energy Intake 134:146 Energy Intake 134:146 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 12 78 theme digestion 1940:1948 arg1 experiments 1950:1960 In-vitro digestion experiments 1931:1960 In-vitro digestion experiments 1931:1960 In-vitro digestion experiments showed that the four IDFs could inhibit the digestion of starch and fat to a certain extent. 35360689 1 79 theme fungi 190:194 arg1 industry 196:203 the edible fungi industry 179:203 the edible fungi industry 179:203 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 9 80 dep low 1517:1519 arg1 to 1514:1515 to 1514:1515 to 1514:1515 The yield of four kinds of IDF from high to low came from Ganoderma lucidum, Hericium erinaceus, Lentinus edodes, and Grifola frondosa. 35360689 2 81 theme large 491:495 arg1 amount 497:502 a large amount 489:502 a large amount of water-insoluble dietary fiber (IDF) 489:541 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 81 theme large 491:495 arg1 IDF 538:540 IDF 538:540 IDF 538:540 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 81 theme large 491:495 arg1 fiber 531:535 water-insoluble dietary fiber 507:535 water-insoluble dietary fiber (IDF) 507:541 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 11 82 theme chemical 1797:1804 arg1 analysis 1806:1813 Physical and chemical analysis 1784:1813 Physical and chemical analysis 1784:1813 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 4 83 from utilization 758:768 arg1 industry 782:789 the food industry 773:789 the food industry 773:789 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 4 84 theme physicochemical 824:838 arg1 properties 840:849 physicochemical properties 824:849 physicochemical properties 824:849 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 6 85 theme fungi 1133:1137 arg1 residues 1139:1146 edible fungi residues 1126:1146 edible fungi residues 1126:1146 The results showed that IDF in the four kinds of edible fungi residues was similar in composition but different in texture. 35360689 5 86 theme edible 981:986 arg1 fungi 988:992 four edible fungi 976:992 four edible fungi 976:992 The IDF from the residues of polysaccharides extracted from four edible fungi was extracted using the Association of Official Analytical Chemists (AOAC) method. 35360689 2 87 theme fiber 531:535 arg1 amount 497:502 a large amount 489:502 a large amount of water-insoluble dietary fiber (IDF) 489:541 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 87 theme fiber 531:535 arg1 IDF 538:540 IDF 538:540 IDF 538:540 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 87 theme fiber 531:535 arg1 fiber 531:535 water-insoluble dietary fiber 507:535 water-insoluble dietary fiber (IDF) 507:541 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 7 88 theme edible 1275:1280 arg1 fungi 1282:1286 edible fungi 1275:1286 edible fungi 1275:1286 Cellulose and hemicellulose are the main IDF extracted from four kinds of edible fungi. 35360689 6 89 from similar 1152:1158 arg1 composition 1163:1173 composition 1163:1173 composition 1163:1173 The results showed that IDF in the four kinds of edible fungi residues was similar in composition but different in texture. 35360689 4 90 dep develop 708:714 arg1 expand 735:740 expand 735:740 expand their potential utilization in the food industry 735:789 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 4 91 from characterization 806:821 arg1 intake 895:900 dietary energy intake 880:900 dietary energy intake 880:900 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 13 92 theme ideal 2090:2094 arg1 material 2096:2103 an ideal material 2087:2103 an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions 2087:2269 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 13 92 theme ideal 2090:2094 arg1 By-products 2055:2065 By-products 2055:2065 By-products of edible fungi 2055:2081 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 11 93 theme oil 1909:1911 arg1 capacity 1921:1928 oil holding capacity 1909:1928 oil holding capacity 1909:1928 Physical and chemical analysis showed that all the four IDFs had certain water holding capacity, water binding capacity, and oil holding capacity. 35360689 8 94 theme Grifola 1424:1430 arg1 frondosa 1432:1439 Grifola frondosa 1424:1439 Grifola frondosa 1424:1439 Among them, Hericium erinaceus is the softest without obvious granular texture, following Lentinus edodes, while Ganoderma lucidum and Grifola frondosa have a relatively hard texture. 35360689 0 95 theme Physicochemical 85:99 arg1 Properties 101:110 Physicochemical Properties 85:110 Physicochemical Properties 85:110 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 5 96 theme method 1069:1074 arg1 Association 1018:1028 the Association 1014:1028 the Association of Official Analytical Chemists (AOAC) method 1014:1074 The IDF from the residues of polysaccharides extracted from four edible fungi was extracted using the Association of Official Analytical Chemists (AOAC) method. 35360689 6 97 from IDF 1101:1103 arg1 kinds 1117:1121 the four kinds 1108:1121 the four kinds of edible fungi residues 1108:1146 The results showed that IDF in the four kinds of edible fungi residues was similar in composition but different in texture. 35360689 5 98 theme Official 1033:1040 arg1 method 1069:1074 Official Analytical Chemists (AOAC) method 1033:1074 Official Analytical Chemists (AOAC) method 1033:1074 The IDF from the residues of polysaccharides extracted from four edible fungi was extracted using the Association of Official Analytical Chemists (AOAC) method. 35360689 4 99 theme energy 888:893 arg1 intake 895:900 dietary energy intake 880:900 dietary energy intake 880:900 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 4 100 theme IDF 873:875 arg1 influence 860:868 the influence 856:868 the influence of IDF on dietary energy intake 856:900 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 4 100 theme IDF 873:875 arg1 characterization 806:821 the structure characterization 792:821 the structure characterization 792:821 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 4 100 theme IDF 873:875 arg1 properties 840:849 physicochemical properties 824:849 physicochemical properties 824:849 In order to develop these by-products, expand their potential utilization in the food industry, the structure characterization, physicochemical properties, and the influence of IDF on dietary energy intake were studied. 35360689 0 101 theme Dietary 10:16 arg1 Fibers 18:23 Insoluble Dietary Fibers 0:23 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 0:147 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 5 102 theme Chemists 1053:1060 arg1 method 1069:1074 Official Analytical Chemists (AOAC) method 1033:1074 Official Analytical Chemists (AOAC) method 1033:1074 The IDF from the residues of polysaccharides extracted from four edible fungi was extracted using the Association of Official Analytical Chemists (AOAC) method. 35360689 13 103 theme physicochemical 2216:2230 arg1 properties 2232:2241 their physicochemical properties 2210:2241 their physicochemical properties 2210:2241 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 9 104 from low 1517:1519 arg1 yield 1477:1481 The yield 1473:1481 The yield of four kinds of IDF from high to low 1473:1519 The yield of four kinds of IDF from high to low came from Ganoderma lucidum, Hericium erinaceus, Lentinus edodes, and Grifola frondosa. 35360689 7 105 theme main 1237:1240 arg1 IDF 1242:1244 the main IDF 1233:1244 the main IDF extracted from four kinds of edible fungi 1233:1286 Cellulose and hemicellulose are the main IDF extracted from four kinds of edible fungi. 35360689 7 105 theme main 1237:1240 arg1 hemicellulose 1215:1227 hemicellulose 1215:1227 hemicellulose 1215:1227 Cellulose and hemicellulose are the main IDF extracted from four kinds of edible fungi. 35360689 7 105 theme main 1237:1240 arg1 Cellulose 1201:1209 Cellulose 1201:1209 Cellulose 1201:1209 Cellulose and hemicellulose are the main IDF extracted from four kinds of edible fungi. 35360689 2 106 theme polysaccharide 406:419 arg1 extraction 421:430 polysaccharide extraction 406:430 polysaccharide extraction by water 406:439 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 1 107 theme resource 244:251 arg1 utilization 253:263 the resource utilization 240:263 the resource utilization of edible fungi by-products 240:291 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 2 108 theme fungi 394:398 arg1 residue 376:382 The waste residue 366:382 The waste residue of edible fungi after polysaccharide extraction by water 366:439 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 108 theme fungi 394:398 arg1 fungi 394:398 edible fungi 387:398 edible fungi 387:398 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 13 109 theme fungi 2077:2081 arg1 material 2096:2103 an ideal material 2087:2103 an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions 2087:2269 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 13 109 theme fungi 2077:2081 arg1 By-products 2055:2065 By-products 2055:2065 By-products of edible fungi 2055:2081 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 10 110 theme functional 1711:1720 arg1 groups 1722:1727 similar functional groups 1703:1727 similar functional groups 1703:1727 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 12 111 theme starch 2019:2024 arg1 digestion 2006:2014 the digestion 2002:2014 the digestion of starch and fat to a certain extent 2002:2052 In-vitro digestion experiments showed that the four IDFs could inhibit the digestion of starch and fat to a certain extent. 35360689 2 112 theme waste 370:374 arg1 residue 376:382 The waste residue 366:382 The waste residue of edible fungi after polysaccharide extraction by water 366:439 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 2 112 theme waste 370:374 arg1 fungi 394:398 edible fungi 387:398 edible fungi 387:398 The waste residue of edible fungi after polysaccharide extraction by water accounts for a large proportion, which contains a large amount of water-insoluble dietary fiber (IDF). 35360689 0 113 theme Fungi 52:56 arg1 Industry 58:65 Edible Fungi Industry 45:65 Edible Fungi Industry 45:65 Insoluble Dietary Fibers From By-Products of Edible Fungi Industry: Basic Structure, Physicochemical Properties, and Their Effects on Energy Intake. 35360689 1 114 theme fungi 275:279 arg1 by-products 281:291 edible fungi by-products 268:291 edible fungi by-products 268:291 With the rapid development of the edible fungi industry in the world, especially in China, the resource utilization of edible fungi by-products has become an urgent problem for the industry's sustainable development. 35360689 13 115 contain have 2137:2140 arg1 IDFs 2125:2128 IDFs 2125:2128 IDFs 2125:2128 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 13 115 contain have 2137:2140 arg2 potential 2146:2154 the potential to be processed into functional food materials due to their physicochemical properties and physiological functions 2142:2269 the potential to be processed into functional food materials due to their physicochemical properties and physiological functions 2142:2269 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35360689 10 116 contain had 1699:1701 arg1 IDFs 1694:1697 the four IDFs 1685:1697 the four IDFs 1685:1697 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 10 116 contain had 1699:1701 arg2 groups 1722:1727 similar functional groups 1703:1727 similar functional groups 1703:1727 Fourier transform IR (FTIR) and X-ray diffraction (XRD) spectra showed that the four IDFs had similar functional groups and all of them contained a large amount of cellulose. 35360689 12 117 theme fat 2030:2032 arg1 digestion 2006:2014 the digestion 2002:2014 the digestion of starch and fat to a certain extent 2002:2052 In-vitro digestion experiments showed that the four IDFs could inhibit the digestion of starch and fat to a certain extent. 35360689 13 118 theme functional 2177:2186 arg1 materials 2193:2201 functional food materials 2177:2201 functional food materials due to their physicochemical properties and physiological functions 2177:2269 By-products of edible fungi are an ideal material for the recovery of IDFs, which have the potential to be processed into functional food materials due to their physicochemical properties and physiological functions. 35993272 0 0 link N-linked 112:119 arg1 glycopeptides 121:133 N-linked glycopeptides 112:133 N-linked glycopeptides 112:133 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 2 1 theme organic 404:410 arg1 frameworks 412:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks 336:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) 336:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 4 2 theme large 894:898 arg1 mg-1 928:931 200 μg mg-1 921:931 200 μg mg-1 921:931 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 4 2 theme large 894:898 arg1 capacity 911:918 large adsorption capacity 894:918 large adsorption capacity (200 μg mg-1) 894:932 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 6 3 theme glycoproteomic 1495:1508 arg1 analysis 1510:1517 glycoproteomic analysis 1495:1517 glycoproteomic analysis of complex biological samples 1495:1547 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 5 4 theme N-glycosylation 1135:1149 arg1 peptides 1151:1158 308 N-glycosylation peptides 1131:1158 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites 1131:1234 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 1 5 theme mass 220:223 arg1 spectrometry 225:236 mass spectrometry 220:236 mass spectrometry 220:236 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 35993272 3 6 theme high 600:603 arg1 stability 605:613 inherent high stability 591:613 inherent high stability 591:613 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 6 7 theme @ 1457:1457 arg1 GSH 1458:1460 the HFH-COFs@Au@GSH 1442:1460 the HFH-COFs@Au@GSH 1442:1460 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 1 8 from research 312:319 arg1 essential 241:249 essential 241:249 essential 241:249 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 35993272 3 9 theme hollow 647:652 arg1 structure 654:662 the hierarchical flower-like hollow structure 618:662 the hierarchical flower-like hollow structure 618:662 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 6 10 used used 1279:1282 arg2 analyses 1265:1272 Gene ontology analyses 1251:1272 Gene ontology analyses 1251:1272 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 5 11 gly glycopeptides 1097:1109 arg2 glycopeptides 1097:1109 N-linked glycopeptides 1088:1109 N-linked glycopeptides in human serum 1088:1124 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 6 12 theme ontology 1256:1263 arg1 analyses 1265:1272 Gene ontology analyses 1251:1272 Gene ontology analyses 1251:1272 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 3 13 theme hierarchical 622:633 arg1 structure 654:662 the hierarchical flower-like hollow structure 618:662 the hierarchical flower-like hollow structure 618:662 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 1 14 from essential 241:249 arg1 research 312:319 disease biomarker research 294:319 disease biomarker research 294:319 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 35993272 4 15 theme HFH-COFs 747:754 arg1 GSH 759:761 The HFH-COFs@Au@GSH 743:761 The HFH-COFs@Au@GSH 743:761 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 6 16 theme human 1392:1396 arg1 serum 1398:1402 human serum 1392:1402 human serum 1392:1402 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 6 17 gly N-glycopeptide 1465:1478 arg2 N-glycopeptide 1465:1478 N-glycopeptide enrichment 1465:1489 N-glycopeptide enrichment 1465:1489 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 3 18 theme large 667:671 arg1 number 673:678 a large number 665:678 a large number of Au NPs and hydrophilic GSH 665:708 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 6 19 theme biological 1530:1539 arg1 samples 1541:1547 complex biological samples 1522:1547 complex biological samples 1522:1547 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 1 20 theme N-glycopeptides 167:181 arg1 enrichment 153:162 Highly efficient enrichment 136:162 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry 136:236 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 35993272 5 21 theme @ 1046:1046 arg1 GSH 1047:1049 the HFH-COFs@Au@GSH 1031:1049 the HFH-COFs@Au@GSH 1031:1049 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 1 22 theme complicated 188:198 arg1 biosamples 200:209 complicated biosamples 188:209 complicated biosamples based on mass spectrometry 188:236 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 35993272 4 23 theme HRP 964:966 arg1 BSA 971:973 HRP to BSA 964:973 HRP to BSA 964:973 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 6 24 theme biological 1321:1330 arg1 process 1332:1338 biological process 1321:1338 biological process 1321:1338 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 6 25 from glycoproteins 1375:1387 arg1 serum 1398:1402 human serum 1392:1402 human serum 1392:1402 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 1 26 from biosamples 200:209 arg1 enrichment 153:162 Highly efficient enrichment 136:162 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry 136:236 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 35993272 4 27 theme excellent 773:781 arg1 hydrophilicity 783:796 excellent hydrophilicity 773:796 excellent hydrophilicity 773:796 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 0 28 theme N-linked 112:119 arg1 glycopeptides 121:133 N-linked glycopeptides 112:133 N-linked glycopeptides 112:133 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 6 29 gly glycoproteins 1375:1387 arg1 glycoproteins 1375:1387 detected glycoproteins 1366:1387 detected glycoproteins in human serum 1366:1402 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 2 30 theme HFH-COFs 453:460 arg1 nanoparticles 438:450 Au nanoparticles 435:450 Au nanoparticles (HFH-COFs@Au@GSH) 435:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 2 30 theme HFH-COFs 453:460 arg1 GSH 465:467 HFH-COFs@Au@GSH 453:467 HFH-COFs@Au@GSH 453:467 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 5 31 theme @ 1043:1043 arg1 GSH 1047:1049 the HFH-COFs@Au@GSH 1031:1049 the HFH-COFs@Au@GSH 1031:1049 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 6 32 theme glycoproteins 1375:1387 arg1 component 1310:1318 the cellular component 1297:1318 the cellular component 1297:1318 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 6 32 theme glycoproteins 1375:1387 arg1 process 1332:1338 biological process 1321:1338 biological process 1321:1338 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 6 32 theme glycoproteins 1375:1387 arg1 function 1354:1361 molecular function 1344:1361 molecular function 1344:1361 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 4 33 theme good 981:984 arg1 times 1010:1014 at least 5 times 999:1014 at least 5 times 999:1014 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 4 33 theme good 981:984 arg1 reusability 986:996 good reusability 981:996 good reusability (at least 5 times) 981:1015 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 3 34 theme specific 564:571 arg1 area 581:584 high specific surface area 559:584 high specific surface area 559:584 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 6 35 theme molecular 1344:1352 arg1 function 1354:1361 molecular function 1344:1361 molecular function 1344:1361 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 4 36 theme Au 756:757 arg1 GSH 759:761 The HFH-COFs@Au@GSH 743:761 The HFH-COFs@Au@GSH 743:761 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 0 37 theme Hydrophilic 0:10 arg1 frameworks 69:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks 0:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 0:134 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 0 38 gly glycopeptides 121:133 arg2 glycopeptides 121:133 N-linked glycopeptides 112:133 N-linked glycopeptides 112:133 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 5 39 gly N-glycosylation 1214:1228 arg2 sites 1230:1234 123 N-glycosylation sites 1210:1234 123 N-glycosylation sites 1210:1234 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 5 39 gly N-glycosylation 1214:1228 arg2 123 1210:1212 123 1210:1212 123 1210:1212 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 0 40 theme flower-like 33:43 arg1 frameworks 69:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks 0:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 0:134 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 5 41 theme human 1114:1118 arg1 serum 1120:1124 human serum 1114:1124 human serum 1114:1124 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 3 42 theme NPs 686:688 arg1 number 673:678 a large number 665:678 a large number of Au NPs and hydrophilic GSH 665:708 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 2 43 theme Au 462:463 arg1 nanoparticles 438:450 Au nanoparticles 435:450 Au nanoparticles (HFH-COFs@Au@GSH) 435:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 2 43 theme Au 462:463 arg1 GSH 465:467 HFH-COFs@Au@GSH 453:467 HFH-COFs@Au@GSH 453:467 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 0 44 theme covalent 52:59 arg1 frameworks 69:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks 0:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 0:134 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 6 45 theme detected 1366:1373 arg1 glycoproteins 1375:1387 detected glycoproteins 1366:1387 detected glycoproteins in human serum 1366:1402 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 4 46 theme detection 861:869 arg1 limit 871:875 low detection limit 857:875 low detection limit (0.1 fmol μL-1) 857:891 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 4 46 theme detection 861:869 arg1 fmol 882:885 0.1 fmol μL-1 878:890 0.1 fmol μL-1 878:890 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 2 47 theme covalent 395:402 arg1 frameworks 412:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks 336:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) 336:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 6 48 from process 1332:1338 arg1 serum 1398:1402 human serum 1392:1402 human serum 1392:1402 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 4 49 theme enrichment 813:822 arg1 performance 824:834 remarkable enrichment performance 802:834 remarkable enrichment performance 802:834 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 2 50 theme flower-like 376:386 arg1 frameworks 412:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks 336:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) 336:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 6 51 theme HFH-COFs 1446:1453 arg1 GSH 1458:1460 the HFH-COFs@Au@GSH 1442:1460 the HFH-COFs@Au@GSH 1442:1460 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 3 52 theme hydrophilic 694:704 arg1 GSH 706:708 hydrophilic GSH 694:708 hydrophilic GSH 694:708 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 3 53 theme high 559:562 arg1 area 581:584 high specific surface area 559:584 high specific surface area 559:584 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 6 54 theme great 1423:1427 arg1 potential 1429:1437 the great potential 1419:1437 the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment 1419:1489 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 1 55 theme biomarker 302:310 arg1 research 312:319 disease biomarker research 294:319 disease biomarker research 294:319 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 35993272 4 56 theme μL-1 887:890 arg1 limit 871:875 low detection limit 857:875 low detection limit (0.1 fmol μL-1) 857:891 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 4 56 theme μL-1 887:890 arg1 fmol 882:885 0.1 fmol μL-1 878:890 0.1 fmol μL-1 878:890 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 4 57 dep BSA 971:973 arg1 to 968:969 to 968:969 to 968:969 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 2 58 theme glutathione 336:346 arg1 frameworks 412:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks 336:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) 336:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 3 59 theme abundant 529:536 arg1 structure 654:662 the hierarchical flower-like hollow structure 618:662 the hierarchical flower-like hollow structure 618:662 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 3 59 theme abundant 529:536 arg1 sites 552:556 the abundant accessibility sites 525:556 the abundant accessibility sites 525:556 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 3 60 theme surface 573:579 arg1 area 581:584 high specific surface area 559:584 high specific surface area 559:584 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 5 61 from glycopeptides 1097:1109 arg1 serum 1120:1124 human serum 1114:1124 human serum 1114:1124 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 2 62 theme -modified 353:361 arg1 frameworks 412:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks 336:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) 336:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 6 63 theme N-glycopeptide 1465:1478 arg1 enrichment 1480:1489 N-glycopeptide enrichment 1465:1489 N-glycopeptide enrichment 1465:1489 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 4 64 dep 1  954:955 arg1  1000 957:961  1000 957:961  1000 957:961 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 4 64 dep 1  954:955 arg1 BSA 971:973 HRP to BSA 964:973 HRP to BSA 964:973 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 3 65 theme inherent 591:598 arg1 stability 605:613 inherent high stability 591:613 inherent high stability 591:613 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 6 66 theme GSH 1458:1460 arg1 potential 1429:1437 the great potential 1419:1437 the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment 1419:1489 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 4 67 theme μg 925:926 arg1 mg-1 928:931 200 μg mg-1 921:931 200 μg mg-1 921:931 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 4 67 theme μg 925:926 arg1 capacity 911:918 large adsorption capacity 894:918 large adsorption capacity (200 μg mg-1) 894:932 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 2 68 theme hollow 388:393 arg1 frameworks 412:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks 336:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) 336:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 1 69 gly N-glycopeptides 167:181 arg2 N-glycopeptides 167:181 N-glycopeptides 167:181 N-glycopeptides 167:181 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 35993272 3 70 theme flower-like 635:645 arg1 structure 654:662 the hierarchical flower-like hollow structure 618:662 the hierarchical flower-like hollow structure 618:662 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 6 71 theme Au 1455:1456 arg1 GSH 1458:1460 the HFH-COFs@Au@GSH 1442:1460 the HFH-COFs@Au@GSH 1442:1460 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 1 72 theme biomedical 255:264 arg1 applications 266:277 biomedical applications 255:277 biomedical applications 255:277 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 35993272 6 73 from serum 1398:1402 arg1 component 1310:1318 the cellular component 1297:1318 the cellular component 1297:1318 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 6 73 from serum 1398:1402 arg1 process 1332:1338 biological process 1321:1338 biological process 1321:1338 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 6 73 from serum 1398:1402 arg1 function 1354:1361 molecular function 1344:1361 molecular function 1344:1361 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 1 74 theme efficient 143:151 arg1 enrichment 153:162 Highly efficient enrichment 136:162 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry 136:236 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 35993272 4 75 theme adsorption 900:909 arg1 mg-1 928:931 200 μg mg-1 921:931 200 μg mg-1 921:931 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 4 75 theme adsorption 900:909 arg1 capacity 911:918 large adsorption capacity 894:918 large adsorption capacity (200 μg mg-1) 894:932 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 5 76 theme N-glycosylation 1214:1228 arg1 sites 1230:1234 123 N-glycosylation sites 1210:1234 123 N-glycosylation sites 1210:1234 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 6 77 theme Gene 1251:1254 arg1 analyses 1265:1272 Gene ontology analyses 1251:1272 Gene ontology analyses 1251:1272 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 6 78 from function 1354:1361 arg1 serum 1398:1402 human serum 1392:1402 human serum 1392:1402 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 6 79 theme samples 1541:1547 arg1 analysis 1510:1517 glycoproteomic analysis 1495:1517 glycoproteomic analysis of complex biological samples 1495:1547 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 0 80 theme efficient 91:99 arg1 capture 101:107 highly efficient capture 84:107 highly efficient capture of N-linked glycopeptides 84:133 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 3 81 theme structure 654:662 arg1 structure 654:662 the hierarchical flower-like hollow structure 618:662 the hierarchical flower-like hollow structure 618:662 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 3 81 theme structure 654:662 arg1 stability 605:613 inherent high stability 591:613 inherent high stability 591:613 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 3 81 theme structure 654:662 arg1 area 581:584 high specific surface area 559:584 high specific surface area 559:584 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 3 81 theme structure 654:662 arg1 sites 552:556 the abundant accessibility sites 525:556 the abundant accessibility sites 525:556 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 6 82 theme complex 1522:1528 arg1 samples 1541:1547 complex biological samples 1522:1547 complex biological samples 1522:1547 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 5 83 theme N-glycosylation 1180:1194 arg1 proteins 1196:1203 84 N-glycosylation proteins 1177:1203 84 N-glycosylation proteins with 123 N-glycosylation sites 1177:1234 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 0 84 theme glycopeptides 121:133 arg1 capture 101:107 highly efficient capture 84:107 highly efficient capture of N-linked glycopeptides 84:133 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 5 85 with proteins 1196:1203 arg1 sites 1230:1234 123 N-glycosylation sites 1210:1234 123 N-glycosylation sites 1210:1234 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 4 86 theme great 935:939 arg1 1  954:955 1  954:955 1  954:955 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 4 86 theme great 935:939 arg1 selectivity 941:951 great selectivity 935:951 great selectivity (1 : 1000, HRP to BSA) 935:974 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 6 87 theme cellular 1301:1308 arg1 component 1310:1318 the cellular component 1297:1318 the cellular component 1297:1318 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 5 88 theme HFH-COFs 1035:1042 arg1 GSH 1047:1049 the HFH-COFs@Au@GSH 1031:1049 the HFH-COFs@Au@GSH 1031:1049 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 4 89 gly N-glycopeptides 840:854 arg2 N-glycopeptides 840:854 N-glycopeptides 840:854 N-glycopeptides 840:854 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 5 90 theme Au 1044:1045 arg1 GSH 1047:1049 the HFH-COFs@Au@GSH 1031:1049 the HFH-COFs@Au@GSH 1031:1049 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 4 91 theme @ 755:755 arg1 GSH 759:761 The HFH-COFs@Au@GSH 743:761 The HFH-COFs@Au@GSH 743:761 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 2 92 theme Au 435:436 arg1 nanoparticles 438:450 Au nanoparticles 435:450 Au nanoparticles (HFH-COFs@Au@GSH) 435:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 2 92 theme Au 435:436 arg1 GSH 465:467 HFH-COFs@Au@GSH 453:467 HFH-COFs@Au@GSH 453:467 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 0 93 theme hollow 45:50 arg1 frameworks 69:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks 0:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 0:134 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 6 94 from component 1310:1318 arg1 serum 1398:1402 human serum 1392:1402 human serum 1392:1402 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 3 95 theme Au 683:684 arg1 NPs 686:688 Au NPs 683:688 Au NPs 683:688 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 4 96 theme @ 758:758 arg1 GSH 759:761 The HFH-COFs@Au@GSH 743:761 The HFH-COFs@Au@GSH 743:761 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 2 97 theme @ 464:464 arg1 nanoparticles 438:450 Au nanoparticles 435:450 Au nanoparticles (HFH-COFs@Au@GSH) 435:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 2 97 theme @ 464:464 arg1 GSH 465:467 HFH-COFs@Au@GSH 453:467 HFH-COFs@Au@GSH 453:467 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 0 98 theme organic 61:67 arg1 frameworks 69:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks 0:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 0:134 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 2 99 theme @ 461:461 arg1 nanoparticles 438:450 Au nanoparticles 435:450 Au nanoparticles (HFH-COFs@Au@GSH) 435:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 2 99 theme @ 461:461 arg1 GSH 465:467 HFH-COFs@Au@GSH 453:467 HFH-COFs@Au@GSH 453:467 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 2 100 gly N-glycopeptide 491:504 arg2 N-glycopeptide 491:504 N-glycopeptide 491:504 N-glycopeptide 491:504 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 5 101 link N-linked 1088:1095 arg1 glycopeptides 1097:1109 N-linked glycopeptides 1088:1109 N-linked glycopeptides in human serum 1088:1124 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 2 102 theme N-glycopeptide 491:504 arg1 enrichment 506:515 N-glycopeptide enrichment 491:515 N-glycopeptide enrichment 491:515 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 3 103 theme GSH 706:708 arg1 number 673:678 a large number 665:678 a large number of Au NPs and hydrophilic GSH 665:708 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 4 104 theme low 857:859 arg1 limit 871:875 low detection limit 857:875 low detection limit (0.1 fmol μL-1) 857:891 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 4 104 theme low 857:859 arg1 fmol 882:885 0.1 fmol μL-1 878:890 0.1 fmol μL-1 878:890 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 3 105 theme accessibility 538:550 arg1 structure 654:662 the hierarchical flower-like hollow structure 618:662 the hierarchical flower-like hollow structure 618:662 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 3 105 theme accessibility 538:550 arg1 sites 552:556 the abundant accessibility sites 525:556 the abundant accessibility sites 525:556 Due to the abundant accessibility sites, high specific surface area, and inherent high stability of the hierarchical flower-like hollow structure, a large number of Au NPs and hydrophilic GSH can be modified on the HFH-COFs. 35993272 6 106 theme @ 1454:1454 arg1 GSH 1458:1460 the HFH-COFs@Au@GSH 1442:1460 the HFH-COFs@Au@GSH 1442:1460 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 5 107 theme N-linked 1088:1095 arg1 glycopeptides 1097:1109 N-linked glycopeptides 1088:1109 N-linked glycopeptides in human serum 1088:1124 Furthermore, the HFH-COFs@Au@GSH were successfully applied to capture N-linked glycopeptides in human serum, and 308 N-glycosylation peptides corresponding to 84 N-glycosylation proteins with 123 N-glycosylation sites were detected. 35993272 4 108 theme remarkable 802:811 arg1 performance 824:834 remarkable enrichment performance 802:834 remarkable enrichment performance 802:834 The HFH-COFs@Au@GSH displayed excellent hydrophilicity and remarkable enrichment performance for N-glycopeptides: low detection limit (0.1 fmol μL-1), large adsorption capacity (200 μg mg-1), great selectivity (1 : 1000, HRP to BSA), and good reusability (at least 5 times). 35993272 2 109 theme hierarchical 363:374 arg1 frameworks 412:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks 336:421 glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) 336:468 In this work, glutathione (GSH)-modified hierarchical flower-like hollow covalent organic frameworks loaded with Au nanoparticles (HFH-COFs@Au@GSH) were synthesized for N-glycopeptide enrichment. 35993272 6 110 from potential 1429:1437 arg1 enrichment 1480:1489 N-glycopeptide enrichment 1465:1489 N-glycopeptide enrichment 1465:1489 Gene ontology analyses were used to elucidate the cellular component, biological process and molecular function of detected glycoproteins in human serum, demonstrating the great potential of the HFH-COFs@Au@GSH in N-glycopeptide enrichment for glycoproteomic analysis of complex biological samples. 35993272 0 111 theme glutathione-modified 12:31 arg1 frameworks 69:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks 0:78 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 0:134 Hydrophilic glutathione-modified flower-like hollow covalent organic frameworks for highly efficient capture of N-linked glycopeptides. 35993272 1 112 theme disease 294:300 arg1 research 312:319 disease biomarker research 294:319 disease biomarker research 294:319 Highly efficient enrichment of N-glycopeptides from complicated biosamples based on mass spectrometry is essential for biomedical applications, especially in disease biomarker research. 36778495 5 0 theme colonic 813:819 arg1 mucus 821:825 colonic mucus 813:825 colonic mucus 813:825 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 1 1 theme hematopoietic 187:199 arg1 transplantation 211:225 allogeneic hematopoietic stem cell transplantation 176:225 allogeneic hematopoietic stem cell transplantation 176:225 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 5 2 theme mucus 821:825 arg1 degradation 798:808 degradation 798:808 degradation of colonic mucus 798:825 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 1 3 theme stem 201:204 arg1 transplantation 211:225 allogeneic hematopoietic stem cell transplantation 176:225 allogeneic hematopoietic stem cell transplantation 176:225 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 5 4 theme Bacteroides 1006:1016 arg1 thetaiotaomicron 1018:1033 Bacteroides thetaiotaomicron 1006:1033 Bacteroides thetaiotaomicron 1006:1033 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 5 5 theme GVHD-related 1046:1057 arg1 mortality 1059:1067 GVHD-related mortality 1046:1067 GVHD-related mortality 1046:1067 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 5 6 theme Bacteroides 771:781 arg1 ovatus 783:788 Bacteroides ovatus 771:788 Bacteroides ovatus 771:788 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 1 7 theme Acute 97:101 arg1 complication 160:171 a serious complication 150:171 a serious complication of allogeneic hematopoietic stem cell transplantation 150:225 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 1 7 theme Acute 97:101 arg1 aGI-GVHD 137:144 aGI-GVHD 137:144 aGI-GVHD 137:144 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 1 7 theme Acute 97:101 arg1 GVHD 131:134 Acute gastrointestinal intestinal GVHD 97:134 Acute gastrointestinal intestinal GVHD (aGI-GVHD) 97:145 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 3 8 theme carbapenem 569:578 arg1 antibiotics 580:590 carbapenem antibiotics 569:590 carbapenem antibiotics 569:590 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 3 9 from microbiome 632:641 arg1 loss 596:599 loss 596:599 loss of Bacteroides ovatus from the microbiome 596:641 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 3 9 from microbiome 632:641 arg1 antibiotics 580:590 carbapenem antibiotics 569:590 carbapenem antibiotics 569:590 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 4 10 theme mouse 649:653 arg1 model 655:659 a mouse model 647:659 a mouse model of carbapenem-aggravated GVHD 647:689 In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. 36778495 1 11 theme gastrointestinal 103:118 arg1 complication 160:171 a serious complication 150:171 a serious complication of allogeneic hematopoietic stem cell transplantation 150:225 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 1 11 theme gastrointestinal 103:118 arg1 aGI-GVHD 137:144 aGI-GVHD 137:144 aGI-GVHD 137:144 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 1 11 theme gastrointestinal 103:118 arg1 GVHD 131:134 Acute gastrointestinal intestinal GVHD 97:134 Acute gastrointestinal intestinal GVHD (aGI-GVHD) 97:145 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 1 12 theme cell 206:209 arg1 transplantation 211:225 allogeneic hematopoietic stem cell transplantation 176:225 allogeneic hematopoietic stem cell transplantation 176:225 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 0 13 theme graft-versus-host 70:86 arg1 disease 88:94 dysbiotic microbiota-induced intestinal graft-versus-host disease 30:94 dysbiotic microbiota-induced intestinal graft-versus-host disease 30:94 Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease. 36778495 1 14 theme intestinal 120:129 arg1 complication 160:171 a serious complication 150:171 a serious complication of allogeneic hematopoietic stem cell transplantation 150:225 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 1 14 theme intestinal 120:129 arg1 aGI-GVHD 137:144 aGI-GVHD 137:144 aGI-GVHD 137:144 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 1 14 theme intestinal 120:129 arg1 GVHD 131:134 Acute gastrointestinal intestinal GVHD 97:134 Acute gastrointestinal intestinal GVHD (aGI-GVHD) 97:145 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 1 15 theme transplantation 211:225 arg1 complication 160:171 a serious complication 150:171 a serious complication of allogeneic hematopoietic stem cell transplantation 150:225 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 1 15 theme transplantation 211:225 arg1 GVHD 131:134 Acute gastrointestinal intestinal GVHD 97:134 Acute gastrointestinal intestinal GVHD (aGI-GVHD) 97:145 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 3 16 with therapy 499:505 arg1 corticosteroids 512:526 corticosteroids 512:526 corticosteroids 512:526 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 2 17 theme aGI-GVHD 348:355 arg1 response 336:343 treatment response 326:343 treatment response of aGI-GVHD 326:355 However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. 36778495 2 17 theme aGI-GVHD 348:355 arg1 microbiota 376:385 the intestinal microbiota 361:385 the intestinal microbiota 361:385 However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. 36778495 4 18 theme Bacteroides 704:714 arg1 ovatus 716:721 Bacteroides ovatus 704:721 Bacteroides ovatus 704:721 In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. 36778495 0 19 theme Bacteroides 0:10 arg1 ovatus 12:17 Bacteroides ovatus 0:17 Bacteroides ovatus 0:17 Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease. 36778495 5 20 theme dietary 920:926 arg1 polysaccharides 928:942 dietary polysaccharides 920:942 dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality 920:1067 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 0 21 theme dysbiotic 30:38 arg1 disease 88:94 dysbiotic microbiota-induced intestinal graft-versus-host disease 30:94 dysbiotic microbiota-induced intestinal graft-versus-host disease 30:94 Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease. 36778495 5 22 theme Bacteroides 860:870 arg1 commensal 849:857 another intestinal commensal 830:857 another intestinal commensal 830:857 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 5 22 theme Bacteroides 860:870 arg1 thetaiotaomicron 872:887 Bacteroides thetaiotaomicron 860:887 Bacteroides thetaiotaomicron 860:887 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 3 23 theme prior 548:552 arg1 treatment 554:562 prior treatment 548:562 prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome 548:641 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 2 24 theme treatment 326:334 arg1 response 336:343 treatment response 326:343 treatment response of aGI-GVHD 326:355 However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. 36778495 1 25 theme intestinal 236:245 arg1 microbiota 247:256 the intestinal microbiota 232:256 the intestinal microbiota 232:256 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 0 26 theme intestinal 59:68 arg1 disease 88:94 dysbiotic microbiota-induced intestinal graft-versus-host disease 30:94 dysbiotic microbiota-induced intestinal graft-versus-host disease 30:94 Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease. 36778495 4 27 theme GVHD 743:746 arg1 severity 731:738 severity 731:738 severity of GVHD 731:746 In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. 36778495 4 28 theme carbapenem-aggravated 664:684 arg1 GVHD 686:689 carbapenem-aggravated GVHD 664:689 carbapenem-aggravated GVHD 664:689 In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. 36778495 3 29 with patients 429:436 arg1 n=37 453:456 n=37 453:456 n=37 453:456 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 3 29 with patients 429:436 arg1 aGI-GVHD 443:450 aGI-GVHD 443:450 aGI-GVHD (n=37) 443:457 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 0 30 theme microbiota-induced 40:57 arg1 disease 88:94 dysbiotic microbiota-induced intestinal graft-versus-host disease 30:94 dysbiotic microbiota-induced intestinal graft-versus-host disease 30:94 Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease. 36778495 3 31 with treatment 554:562 arg1 loss 596:599 loss 596:599 loss of Bacteroides ovatus from the microbiome 596:641 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 3 31 with treatment 554:562 arg1 antibiotics 580:590 carbapenem antibiotics 569:590 carbapenem antibiotics 569:590 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 5 32 theme mucus 985:989 arg1 degradation 991:1001 mucus degradation 985:1001 mucus degradation by Bacteroides thetaiotaomicron 985:1033 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 5 33 theme intestinal 838:847 arg1 commensal 849:857 another intestinal commensal 830:857 another intestinal commensal 830:857 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 5 33 theme intestinal 838:847 arg1 thetaiotaomicron 872:887 Bacteroides thetaiotaomicron 860:887 Bacteroides thetaiotaomicron 860:887 Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality. 36778495 3 34 theme Bacteroides 604:614 arg1 ovatus 616:621 Bacteroides ovatus 604:621 Bacteroides ovatus 604:621 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 3 35 theme patients 429:436 arg1 cohort 419:424 a cohort 417:424 a cohort of patients with aGI-GVHD (n=37) 417:457 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 3 36 theme ovatus 616:621 arg1 loss 596:599 loss 596:599 loss of Bacteroides ovatus from the microbiome 596:641 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 3 36 theme ovatus 616:621 arg1 antibiotics 580:590 carbapenem antibiotics 569:590 carbapenem antibiotics 569:590 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 2 37 theme intestinal 365:374 arg1 microbiota 376:385 the intestinal microbiota 361:385 the intestinal microbiota 361:385 However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. 36778495 1 38 theme serious 152:158 arg1 complication 160:171 a serious complication 150:171 a serious complication of allogeneic hematopoietic stem cell transplantation 150:225 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 1 38 theme serious 152:158 arg1 GVHD 131:134 Acute gastrointestinal intestinal GVHD 97:134 Acute gastrointestinal intestinal GVHD (aGI-GVHD) 97:145 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36778495 3 39 theme standard 490:497 arg1 therapy 499:505 standard therapy 490:505 standard therapy with corticosteroids 490:526 In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. 36778495 4 40 theme GVHD 686:689 arg1 model 655:659 a mouse model 647:659 a mouse model of carbapenem-aggravated GVHD 647:689 In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. 36778495 1 41 theme allogeneic 176:185 arg1 transplantation 211:225 allogeneic hematopoietic stem cell transplantation 176:225 allogeneic hematopoietic stem cell transplantation 176:225 Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. 36897183 6 0 theme antibody-based 1405:1418 arg1 molecules 1420:1428 large-sized IgG antibody-based molecules 1389:1428 large-sized IgG antibody-based molecules 1389:1428 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 6 1 theme improved 1256:1263 arg1 affinities 1273:1282 significantly improved binding affinities 1242:1282 significantly improved binding affinities for hPD-1 ligands 1242:1300 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 2 2 theme small 574:578 arg1 moiety 588:593 a small protein moiety 572:593 a small protein moiety of 14-17 kDa 572:606 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 2 2 theme small 574:578 arg1 ectodomain 560:569 the human PD-1 (hPD-1) ectodomain 537:569 the human PD-1 (hPD-1) ectodomain 537:569 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 4 3 theme high 1058:1061 arg1 affinity 1071:1078 exceptionally high binding affinity 1044:1078 exceptionally high binding affinity to hPD-L1 1044:1088 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 1 4 theme immuno-oncology 249:263 arg1 field 240:244 the field 236:244 the field of immuno-oncology 236:263 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 6 5 theme IgG 1401:1403 arg1 molecules 1420:1428 large-sized IgG antibody-based molecules 1389:1428 large-sized IgG antibody-based molecules 1389:1428 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 1 6 theme additional 415:424 arg1 works 438:442 additional engineering works 415:442 additional engineering works 415:442 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 3 7 theme increased 867:875 arg1 affinity 892:899 1000-fold increased hPD-L1 binding affinity 857:899 1000-fold increased hPD-L1 binding affinity 857:899 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 3 8 theme PD-1 827:830 arg1 variants 832:839 glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants 750:839 glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1 750:935 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 4 9 theme hPD-1 952:956 arg1 variants 958:965 The resulting hPD-1 variants 938:965 The resulting hPD-1 variants 938:965 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 4 9 theme hPD-1 952:956 arg1 JYQ12 982:986 aglycosylated JYQ12 968:986 aglycosylated JYQ12 968:986 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 4 9 theme hPD-1 952:956 arg1 JYQ12-2 992:998 JYQ12-2 992:998 JYQ12-2 with a single-N-linked glycan chain 992:1034 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 1 10 theme engineering 426:436 arg1 works 438:442 additional engineering works 415:442 additional engineering works 415:442 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 4 11 gly aglycosylated 968:980 arg1 variants 958:965 The resulting hPD-1 variants 938:965 The resulting hPD-1 variants 938:965 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 4 11 gly aglycosylated 968:980 arg1 JYQ12 982:986 aglycosylated JYQ12 968:986 aglycosylated JYQ12 968:986 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 3 12 theme hPD-L1 877:882 arg1 affinity 892:899 1000-fold increased hPD-L1 binding affinity 857:899 1000-fold increased hPD-L1 binding affinity 857:899 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 5 13 theme cells 1215:1219 arg1 proliferation 1190:1202 the proliferation 1186:1202 the proliferation of human T cells 1186:1219 Moreover, the JYQ12-2 efficiently potentiated the proliferation of human T cells. 36897183 0 14 theme T 104:104 arg1 Cell 106:109 T Cell 104:109 T Cell 104:109 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands Potentiate T Cell. 36897183 3 15 theme bacterial 667:675 arg1 evolution 716:724 bacterial display-based high-throughput directed evolution 667:724 bacterial display-based high-throughput directed evolution 667:724 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 6 16 theme hPD-1 1288:1292 arg1 ligands 1294:1300 hPD-1 ligands 1288:1300 hPD-1 ligands 1288:1300 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 1 17 theme works 438:442 arg1 kDa 389:391 150 kDa 385:391 150 kDa 385:391 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 1 17 theme works 438:442 arg1 necessity 402:410 the necessity 398:410 the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells 398:509 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 1 17 theme works 438:442 arg1 size 379:382 their large molecular size 357:382 their large molecular size (150 kDa) 357:392 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 1 18 theme large 363:367 arg1 kDa 389:391 150 kDa 385:391 150 kDa 385:391 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 1 18 theme large 363:367 arg1 size 379:382 their large molecular size 357:382 their large molecular size (150 kDa) 357:392 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 2 19 theme kDa 604:606 arg1 moiety 588:593 a small protein moiety 572:593 a small protein moiety of 14-17 kDa 572:606 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 2 19 theme kDa 604:606 arg1 ectodomain 560:569 the human PD-1 (hPD-1) ectodomain 537:569 the human PD-1 (hPD-1) ectodomain 537:569 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 4 20 theme single-N-linked 1007:1021 arg1 chain 1030:1034 a single-N-linked glycan chain 1005:1034 a single-N-linked glycan chain 1005:1034 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 1 21 theme molecular 369:377 arg1 kDa 389:391 150 kDa 385:391 150 kDa 385:391 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 1 21 theme molecular 369:377 arg1 size 379:382 their large molecular size 357:382 their large molecular size (150 kDa) 357:392 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 3 22 used used 662:665 arg2 we 659:660 we 659:660 we 659:660 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 2 23 theme therapeutic 634:644 arg1 agent 646:650 a therapeutic agent 632:650 a therapeutic agent 632:650 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 2 23 theme therapeutic 634:644 arg1 ectodomain 560:569 the human PD-1 (hPD-1) ectodomain 537:569 the human PD-1 (hPD-1) ectodomain 537:569 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 0 24 theme Human 18:22 arg1 Variants 29:36 Glycan-Controlled Human PD-1 Variants 0:36 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands 0:91 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands Potentiate T Cell. 36897183 6 25 theme binding 1265:1271 arg1 affinities 1273:1282 significantly improved binding affinities 1242:1282 significantly improved binding affinities for hPD-1 ligands 1242:1300 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 1 26 theme effector 454:461 arg1 functions 463:471 effector functions 454:471 effector functions for antibodies targeting immune cells 454:509 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 3 27 theme display-based 677:689 arg1 evolution 716:724 bacterial display-based high-throughput directed evolution 667:724 bacterial display-based high-throughput directed evolution 667:724 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 0 28 theme Glycan-Controlled 0:16 arg1 Variants 29:36 Glycan-Controlled Human PD-1 Variants 0:36 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands 0:91 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands Potentiate T Cell. 36897183 5 29 theme human 1207:1211 arg1 cells 1215:1219 human T cells 1207:1219 human T cells 1207:1219 Moreover, the JYQ12-2 efficiently potentiated the proliferation of human T cells. 36897183 2 30 theme protein 580:586 arg1 moiety 588:593 a small protein moiety 572:593 a small protein moiety of 14-17 kDa 572:606 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 2 30 theme protein 580:586 arg1 ectodomain 560:569 the human PD-1 (hPD-1) ectodomain 537:569 the human PD-1 (hPD-1) ectodomain 537:569 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 0 31 dep Ligands 85:91 arg1 to 77:78 to 77:78 to 77:78 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands Potentiate T Cell. 36897183 2 32 theme human 541:545 arg1 hPD-1 553:557 hPD-1 553:557 hPD-1 553:557 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 2 32 theme human 541:545 arg1 PD-1 547:550 human PD-1 541:550 the human PD-1 (hPD-1) ectodomain 537:569 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 6 33 theme hPD-1 1222:1226 arg1 variants 1228:1235 hPD-1 variants 1222:1235 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands 1222:1300 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 6 33 theme hPD-1 1222:1226 arg1 therapeutics 1329:1340 effective therapeutics 1319:1340 effective therapeutics 1319:1340 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 6 33 theme hPD-1 1222:1226 arg1 diagnostics 1345:1355 diagnostics 1345:1355 diagnostics 1345:1355 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 1 34 theme immune 197:202 arg1 checkpoints 204:214 immune checkpoints 197:214 immune checkpoints 197:214 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 0 35 theme PD-1 24:27 arg1 Variants 29:36 Glycan-Controlled Human PD-1 Variants 0:36 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands 0:91 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands Potentiate T Cell. 36897183 3 36 theme high-throughput 691:705 arg1 evolution 716:724 bacterial display-based high-throughput directed evolution 667:724 bacterial display-based high-throughput directed evolution 667:724 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 4 37 with JYQ12 982:986 arg1 chain 1030:1034 a single-N-linked glycan chain 1005:1034 a single-N-linked glycan chain 1005:1034 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 3 38 theme wild-type 921:929 arg1 hPD-1 931:935 wild-type hPD-1 921:935 wild-type hPD-1 921:935 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 1 39 theme checkpoints 204:214 arg1 activity 185:192 the activity 181:192 the activity of immune checkpoints 181:214 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 0 40 theme Broad-Spectrum 49:62 arg1 Ligands 85:91 Broad-Spectrum High Binding to PD-1 Ligands 49:91 Broad-Spectrum High Binding to PD-1 Ligands 49:91 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands Potentiate T Cell. 36897183 3 41 theme directed 707:714 arg1 evolution 716:724 bacterial display-based high-throughput directed evolution 667:724 bacterial display-based high-throughput directed evolution 667:724 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 6 42 used used 1311:1314 arg2 variants 1228:1235 hPD-1 variants 1222:1235 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands 1222:1300 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 6 42 used used 1311:1314 arg2 therapeutics 1329:1340 effective therapeutics 1319:1340 effective therapeutics 1319:1340 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 6 42 used used 1311:1314 arg2 diagnostics 1345:1355 diagnostics 1345:1355 diagnostics 1345:1355 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 3 43 theme glycan-controlled 750:766 arg1 variants 832:839 glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants 750:839 glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1 750:935 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 5 44 theme T 1213:1213 arg1 cells 1215:1219 human T cells 1207:1219 human T cells 1207:1219 Moreover, the JYQ12-2 efficiently potentiated the proliferation of human T cells. 36897183 4 45 with JYQ12-2 992:998 arg1 chain 1030:1034 a single-N-linked glycan chain 1005:1034 a single-N-linked glycan chain 1005:1034 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 0 46 theme Binding 69:75 arg1 Ligands 85:91 Broad-Spectrum High Binding to PD-1 Ligands 49:91 Broad-Spectrum High Binding to PD-1 Ligands 49:91 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands Potentiate T Cell. 36897183 6 47 theme large-sized 1389:1399 arg1 molecules 1420:1428 large-sized IgG antibody-based molecules 1389:1428 large-sized IgG antibody-based molecules 1389:1428 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 4 48 theme aglycosylated 968:980 arg1 variants 958:965 The resulting hPD-1 variants 938:965 The resulting hPD-1 variants 938:965 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 4 48 theme aglycosylated 968:980 arg1 JYQ12 982:986 aglycosylated JYQ12 968:986 aglycosylated JYQ12 968:986 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 3 49 dep glycan-controlled 750:766 arg1 aglycosylated 769:781 aglycosylated 769:781 aglycosylated 769:781 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 3 49 dep glycan-controlled 750:766 arg1 glycosylated 807:818 glycosylated 807:818 glycosylated 807:818 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 1 50 theme therapeutic 121:131 arg1 G 148:148 therapeutic immunoglobulin G 121:148 therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints 121:214 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 1 50 theme therapeutic 121:131 arg1 IgG 151:153 IgG 151:153 IgG 151:153 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 0 51 theme High 64:67 arg1 Ligands 85:91 Broad-Spectrum High Binding to PD-1 Ligands 49:91 Broad-Spectrum High Binding to PD-1 Ligands 49:91 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands Potentiate T Cell. 36897183 6 52 theme effective 1319:1327 arg1 variants 1228:1235 hPD-1 variants 1222:1235 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands 1222:1300 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 6 52 theme effective 1319:1327 arg1 therapeutics 1329:1340 effective therapeutics 1319:1340 effective therapeutics 1319:1340 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 3 53 dep glycosylated 807:818 arg1 single-N-linked 791:805 single-N-linked 791:805 single-N-linked 791:805 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 4 54 link single-N-linked 1007:1021 arg1 chain 1030:1034 a single-N-linked glycan chain 1005:1034 a single-N-linked glycan chain 1005:1034 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 1 55 theme immune 498:503 arg1 cells 505:509 immune cells 498:509 immune cells 498:509 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 1 56 theme immunoglobulin 133:146 arg1 G 148:148 therapeutic immunoglobulin G 121:148 therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints 121:214 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 1 56 theme immunoglobulin 133:146 arg1 IgG 151:153 IgG 151:153 IgG 151:153 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 1 57 theme G 148:148 arg1 antibodies 156:165 therapeutic immunoglobulin G (IgG) antibodies 121:165 therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints 121:214 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 6 58 with variants 1228:1235 arg1 affinities 1273:1282 significantly improved binding affinities 1242:1282 significantly improved binding affinities for hPD-1 ligands 1242:1300 hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules. 36897183 2 59 theme PD-1 547:550 arg1 moiety 588:593 a small protein moiety 572:593 a small protein moiety of 14-17 kDa 572:606 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 2 59 theme PD-1 547:550 arg1 ectodomain 560:569 the human PD-1 (hPD-1) ectodomain 537:569 the human PD-1 (hPD-1) ectodomain 537:569 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 2 59 theme PD-1 547:550 arg1 agent 646:650 a therapeutic agent 632:650 a therapeutic agent 632:650 To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. 36897183 3 60 theme human 821:825 arg1 variants 832:839 glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants 750:839 glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1 750:935 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 4 61 theme high 1099:1102 arg1 affinity 1104:1111 very high affinity 1094:1111 very high affinity to both hPD-L2 and mPD-L1 1094:1137 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 0 62 theme PD-1 80:83 arg1 Ligands 85:91 Broad-Spectrum High Binding to PD-1 Ligands 49:91 Broad-Spectrum High Binding to PD-1 Ligands 49:91 Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands Potentiate T Cell. 36897183 4 63 theme binding 1063:1069 arg1 affinity 1071:1078 exceptionally high binding affinity 1044:1078 exceptionally high binding affinity to hPD-L1 1044:1088 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 4 64 theme glycan 1023:1028 arg1 chain 1030:1034 a single-N-linked glycan chain 1005:1034 a single-N-linked glycan chain 1005:1034 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 1 65 theme tumor 327:331 arg1 microenvironment 333:348 the tumor microenvironment 323:348 the tumor microenvironment 323:348 Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. 36897183 3 66 theme binding 884:890 arg1 affinity 892:899 1000-fold increased hPD-L1 binding affinity 857:899 1000-fold increased hPD-L1 binding affinity 857:899 Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. 36897183 4 67 theme resulting 942:950 arg1 variants 958:965 The resulting hPD-1 variants 938:965 The resulting hPD-1 variants 938:965 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 4 67 theme resulting 942:950 arg1 JYQ12 982:986 aglycosylated JYQ12 968:986 aglycosylated JYQ12 968:986 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36897183 4 67 theme resulting 942:950 arg1 JYQ12-2 992:998 JYQ12-2 992:998 JYQ12-2 with a single-N-linked glycan chain 992:1034 The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. 36963488 0 0 theme sequence 79:86 arg1 bias 102:105 a target sequence compositional bias 70:105 a target sequence compositional bias 70:105 Exploration of O-GlcNAc-transferase (OGT) glycosylation sites reveals a target sequence compositional bias. 36963488 2 1 gly glycosylates 303:314 arg1 range 324:328 a broad range 316:328 a broad range of peptide sequences 316:349 The enzyme glycosylates a broad range of peptide sequences and prediction of glycosylation sites has proven challenging. 36963488 1 2 theme essential 141:149 arg1 enzyme 165:170 an essential glycosylating enzyme 138:170 an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins 138:289 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 1 2 theme essential 141:149 arg1 transferase 117:127 O-GlcNAc transferase 108:127 O-GlcNAc transferase (OGT) 108:133 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 0 3 theme target 72:77 arg1 bias 102:105 a target sequence compositional bias 70:105 a target sequence compositional bias 70:105 Exploration of O-GlcNAc-transferase (OGT) glycosylation sites reveals a target sequence compositional bias. 36963488 6 4 theme protein 906:912 arg1 composition 887:897 the amino acid composition 872:897 the amino acid composition of the protein Fused in sarcoma (FUS) to enhance glycosylation 872:960 This compositional bias was validated by modifying the amino acid composition of the protein Fused in sarcoma (FUS) to enhance glycosylation. 36963488 1 5 theme glycosylating 151:163 arg1 enzyme 165:170 an essential glycosylating enzyme 138:170 an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins 138:289 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 1 5 theme glycosylating 151:163 arg1 transferase 117:127 O-GlcNAc transferase 108:127 O-GlcNAc transferase (OGT) 108:133 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 1 6 theme nuclear 258:264 arg1 proteins 282:289 nuclear and cytoplasmic proteins 258:289 nuclear and cytoplasmic proteins 258:289 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 3 7 theme sites 562:566 arg1 prediction 523:532 prediction 523:532 prediction of legitimate glycosylation sites 523:566 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 0 8 theme compositional 88:100 arg1 bias 102:105 a target sequence compositional bias 70:105 a target sequence compositional bias 70:105 Exploration of O-GlcNAc-transferase (OGT) glycosylation sites reveals a target sequence compositional bias. 36963488 3 9 gly glycosylation 548:560 arg2 sites 562:566 legitimate glycosylation sites 537:566 legitimate glycosylation sites 537:566 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 1 10 theme cytoplasmic 270:280 arg1 proteins 282:289 nuclear and cytoplasmic proteins 258:289 nuclear and cytoplasmic proteins 258:289 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 4 11 theme sequences 696:704 arg1 sequences 696:704 sequences 696:704 sequences that are not glycosylated by OGT 696:737 Here, we tested a number of intrinsically disordered protein regions as substrates of OGT to establish a set of sequences that are not glycosylated by OGT. 36963488 4 11 theme sequences 696:704 arg1 set 689:691 a set 687:691 a set of sequences that are not glycosylated by OGT 687:737 Here, we tested a number of intrinsically disordered protein regions as substrates of OGT to establish a set of sequences that are not glycosylated by OGT. 36963488 7 12 theme glycosylation-promoting 1067:1089 arg1 mutations 1091:1099 glycosylation-promoting mutations 1067:1099 glycosylation-promoting mutations 1067:1099 NMR experiments demonstrate that the tetratricopeptide repeat (TPR) region of OGT can bind FUS and that glycosylation-promoting mutations enhance binding. 36963488 3 13 theme legitimate 537:546 arg1 sites 562:566 legitimate glycosylation sites 537:566 legitimate glycosylation sites 537:566 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 3 14 theme set 452:454 arg1 lack 417:420 The lack 413:420 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT 413:512 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 5 15 theme negative 744:751 arg1 set 758:760 The negative data set 740:760 The negative data set 740:760 The negative data set suggests an amino acid compositional bias for OGT targets. 36963488 6 16 theme acid 882:885 arg1 composition 887:897 the amino acid composition 872:897 the amino acid composition of the protein Fused in sarcoma (FUS) to enhance glycosylation 872:960 This compositional bias was validated by modifying the amino acid composition of the protein Fused in sarcoma (FUS) to enhance glycosylation. 36963488 3 17 theme glycosylation 548:560 arg1 sites 562:566 legitimate glycosylation sites 537:566 legitimate glycosylation sites 537:566 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 4 18 theme OGT 670:672 arg1 substrates 656:665 substrates 656:665 substrates of OGT 656:672 Here, we tested a number of intrinsically disordered protein regions as substrates of OGT to establish a set of sequences that are not glycosylated by OGT. 36963488 4 18 theme OGT 670:672 arg1 number 602:607 a number 600:607 a number of intrinsically disordered protein regions 600:651 Here, we tested a number of intrinsically disordered protein regions as substrates of OGT to establish a set of sequences that are not glycosylated by OGT. 36963488 6 19 theme amino 876:880 arg1 composition 887:897 the amino acid composition 872:897 the amino acid composition of the protein Fused in sarcoma (FUS) to enhance glycosylation 872:960 This compositional bias was validated by modifying the amino acid composition of the protein Fused in sarcoma (FUS) to enhance glycosylation. 36963488 5 20 theme OGT 808:810 arg1 targets 812:818 OGT targets 808:818 OGT targets 808:818 The negative data set suggests an amino acid compositional bias for OGT targets. 36963488 1 21 theme proteins 282:289 arg1 threonine 236:244 threonine 236:244 threonine 236:244 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 1 21 theme proteins 282:289 arg1 serine 226:231 serine 226:231 serine 226:231 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 2 22 theme broad 318:322 arg1 range 324:328 a broad range 316:328 a broad range of peptide sequences 316:349 The enzyme glycosylates a broad range of peptide sequences and prediction of glycosylation sites has proven challenging. 36963488 3 23 theme verified 443:450 arg1 set 452:454 an experimentally verified set 425:454 an experimentally verified set of polypeptide sequences that are not glycosylated by OGT 425:512 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 3 23 theme verified 443:450 arg1 sequences 471:479 polypeptide sequences 459:479 polypeptide sequences that are not glycosylated by OGT 459:512 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 2 24 gly glycosylation 369:381 arg2 sites 383:387 glycosylation sites 369:387 glycosylation sites 369:387 The enzyme glycosylates a broad range of peptide sequences and prediction of glycosylation sites has proven challenging. 36963488 3 25 gly glycosylated 494:505 arg1 sequences 471:479 polypeptide sequences 459:479 polypeptide sequences that are not glycosylated by OGT 459:512 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 0 26 theme O-GlcNAc-transferase 15:34 arg1 sites 56:60 O-GlcNAc-transferase (OGT) glycosylation sites 15:60 O-GlcNAc-transferase (OGT) glycosylation sites 15:60 Exploration of O-GlcNAc-transferase (OGT) glycosylation sites reveals a target sequence compositional bias. 36963488 7 27 theme OGT 1041:1043 arg1 region 1031:1036 the tetratricopeptide repeat (TPR) region 996:1036 the tetratricopeptide repeat (TPR) region of OGT 996:1043 NMR experiments demonstrate that the tetratricopeptide repeat (TPR) region of OGT can bind FUS and that glycosylation-promoting mutations enhance binding. 36963488 1 28 theme O-GlcNAc 108:115 arg1 OGT 130:132 OGT 130:132 OGT 130:132 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 1 28 theme O-GlcNAc 108:115 arg1 transferase 117:127 O-GlcNAc transferase 108:127 O-GlcNAc transferase (OGT) 108:133 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 1 28 theme O-GlcNAc 108:115 arg1 enzyme 165:170 an essential glycosylating enzyme 138:170 an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins 138:289 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 4 29 theme regions 645:651 arg1 substrates 656:665 substrates 656:665 substrates of OGT 656:672 Here, we tested a number of intrinsically disordered protein regions as substrates of OGT to establish a set of sequences that are not glycosylated by OGT. 36963488 4 29 theme regions 645:651 arg1 number 602:607 a number 600:607 a number of intrinsically disordered protein regions 600:651 Here, we tested a number of intrinsically disordered protein regions as substrates of OGT to establish a set of sequences that are not glycosylated by OGT. 36963488 5 30 theme amino 774:778 arg1 bias 799:802 an amino acid compositional bias 771:802 an amino acid compositional bias for OGT targets 771:818 The negative data set suggests an amino acid compositional bias for OGT targets. 36963488 4 31 gly glycosylated 719:730 arg1 sequences 696:704 sequences 696:704 sequences that are not glycosylated by OGT 696:737 Here, we tested a number of intrinsically disordered protein regions as substrates of OGT to establish a set of sequences that are not glycosylated by OGT. 36963488 3 32 theme polypeptide 459:469 arg1 sequences 471:479 polypeptide sequences 459:479 polypeptide sequences that are not glycosylated by OGT 459:512 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 1 33 theme N-acetylglucosamine 203:221 arg1 addition 191:198 the addition 187:198 the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins 187:289 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 5 34 theme acid 780:783 arg1 bias 799:802 an amino acid compositional bias 771:802 an amino acid compositional bias for OGT targets 771:818 The negative data set suggests an amino acid compositional bias for OGT targets. 36963488 8 35 theme particular 1212:1221 arg1 compositions 1223:1234 particular compositions 1212:1234 particular compositions 1212:1234 These results provide evidence that the TPR recognizes disordered segments of substrates with particular compositions to promote glycosylation, providing insight into the broad specificity of OGT. 36963488 1 36 dep serine 226:231 arg1 residues 246:253 residues 246:253 residues 246:253 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 7 37 theme repeat 1018:1023 arg1 region 1031:1036 the tetratricopeptide repeat (TPR) region 996:1036 the tetratricopeptide repeat (TPR) region of OGT 996:1043 NMR experiments demonstrate that the tetratricopeptide repeat (TPR) region of OGT can bind FUS and that glycosylation-promoting mutations enhance binding. 36963488 3 38 theme sequences 471:479 arg1 set 452:454 an experimentally verified set 425:454 an experimentally verified set of polypeptide sequences that are not glycosylated by OGT 425:512 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 3 38 theme sequences 471:479 arg1 sequences 471:479 polypeptide sequences 459:479 polypeptide sequences that are not glycosylated by OGT 459:512 The lack of an experimentally verified set of polypeptide sequences that are not glycosylated by OGT has made prediction of legitimate glycosylation sites more difficult. 36963488 0 39 theme sites 56:60 arg1 Exploration 0:10 Exploration 0:10 Exploration of O-GlcNAc-transferase (OGT) glycosylation sites 0:60 Exploration of O-GlcNAc-transferase (OGT) glycosylation sites reveals a target sequence compositional bias. 36963488 8 40 theme OGT 1310:1312 arg1 specificity 1295:1305 the broad specificity 1285:1305 the broad specificity of OGT 1285:1312 These results provide evidence that the TPR recognizes disordered segments of substrates with particular compositions to promote glycosylation, providing insight into the broad specificity of OGT. 36963488 0 41 theme glycosylation 42:54 arg1 sites 56:60 O-GlcNAc-transferase (OGT) glycosylation sites 15:60 O-GlcNAc-transferase (OGT) glycosylation sites 15:60 Exploration of O-GlcNAc-transferase (OGT) glycosylation sites reveals a target sequence compositional bias. 36963488 2 42 theme sequences 341:349 arg1 range 324:328 a broad range 316:328 a broad range of peptide sequences 316:349 The enzyme glycosylates a broad range of peptide sequences and prediction of glycosylation sites has proven challenging. 36963488 1 43 gly glycosylating 151:163 arg0 enzyme 165:170 an essential glycosylating enzyme 138:170 an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins 138:289 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 1 43 gly glycosylating 151:163 arg0 transferase 117:127 O-GlcNAc transferase 108:127 O-GlcNAc transferase (OGT) 108:133 O-GlcNAc transferase (OGT) is an essential glycosylating enzyme that catalyzes the addition of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. 36963488 7 44 theme tetratricopeptide 1000:1016 arg1 TPR 1026:1028 TPR 1026:1028 TPR 1026:1028 NMR experiments demonstrate that the tetratricopeptide repeat (TPR) region of OGT can bind FUS and that glycosylation-promoting mutations enhance binding. 36963488 7 44 theme tetratricopeptide 1000:1016 arg1 repeat 1018:1023 tetratricopeptide repeat 1000:1023 the tetratricopeptide repeat (TPR) region of OGT 996:1043 NMR experiments demonstrate that the tetratricopeptide repeat (TPR) region of OGT can bind FUS and that glycosylation-promoting mutations enhance binding. 36963488 2 45 theme peptide 333:339 arg1 sequences 341:349 peptide sequences 333:349 peptide sequences 333:349 The enzyme glycosylates a broad range of peptide sequences and prediction of glycosylation sites has proven challenging. 36963488 8 46 with segments 1184:1191 arg1 compositions 1223:1234 particular compositions 1212:1234 particular compositions 1212:1234 These results provide evidence that the TPR recognizes disordered segments of substrates with particular compositions to promote glycosylation, providing insight into the broad specificity of OGT. 36963488 6 47 theme compositional 826:838 arg1 bias 840:843 This compositional bias 821:843 This compositional bias 821:843 This compositional bias was validated by modifying the amino acid composition of the protein Fused in sarcoma (FUS) to enhance glycosylation. 36963488 5 48 theme data 753:756 arg1 set 758:760 The negative data set 740:760 The negative data set 740:760 The negative data set suggests an amino acid compositional bias for OGT targets. 36963488 8 49 theme broad 1289:1293 arg1 specificity 1295:1305 the broad specificity 1285:1305 the broad specificity of OGT 1285:1312 These results provide evidence that the TPR recognizes disordered segments of substrates with particular compositions to promote glycosylation, providing insight into the broad specificity of OGT. 36963488 0 50 gly glycosylation 42:54 arg2 sites 56:60 O-GlcNAc-transferase (OGT) glycosylation sites 15:60 O-GlcNAc-transferase (OGT) glycosylation sites 15:60 Exploration of O-GlcNAc-transferase (OGT) glycosylation sites reveals a target sequence compositional bias. 36963488 8 51 theme disordered 1173:1182 arg1 segments 1184:1191 disordered segments 1173:1191 disordered segments of substrates with particular compositions 1173:1234 These results provide evidence that the TPR recognizes disordered segments of substrates with particular compositions to promote glycosylation, providing insight into the broad specificity of OGT. 36963488 2 52 theme sites 383:387 arg1 prediction 355:364 prediction 355:364 prediction of glycosylation sites 355:387 The enzyme glycosylates a broad range of peptide sequences and prediction of glycosylation sites has proven challenging. 36963488 4 53 theme protein 637:643 arg1 regions 645:651 intrinsically disordered protein regions 612:651 intrinsically disordered protein regions 612:651 Here, we tested a number of intrinsically disordered protein regions as substrates of OGT to establish a set of sequences that are not glycosylated by OGT. 36963488 5 54 theme compositional 785:797 arg1 bias 799:802 an amino acid compositional bias 771:802 an amino acid compositional bias for OGT targets 771:818 The negative data set suggests an amino acid compositional bias for OGT targets. 36963488 8 55 theme substrates 1196:1205 arg1 segments 1184:1191 disordered segments 1173:1191 disordered segments of substrates with particular compositions 1173:1234 These results provide evidence that the TPR recognizes disordered segments of substrates with particular compositions to promote glycosylation, providing insight into the broad specificity of OGT. 36963488 7 56 theme NMR 963:965 arg1 experiments 967:977 NMR experiments 963:977 NMR experiments 963:977 NMR experiments demonstrate that the tetratricopeptide repeat (TPR) region of OGT can bind FUS and that glycosylation-promoting mutations enhance binding. 36963488 2 57 theme glycosylation 369:381 arg1 sites 383:387 glycosylation sites 369:387 glycosylation sites 369:387 The enzyme glycosylates a broad range of peptide sequences and prediction of glycosylation sites has proven challenging. 36963488 4 58 theme disordered 626:635 arg1 regions 645:651 intrinsically disordered protein regions 612:651 intrinsically disordered protein regions 612:651 Here, we tested a number of intrinsically disordered protein regions as substrates of OGT to establish a set of sequences that are not glycosylated by OGT. 36840027 8 0 dep Greater 1042:1048 arg1 proliferation 1059:1071 in vitro proliferation 1050:1071 Greater in vitro proliferation of dental pulp mesenchymal stem cells 1042:1109 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 4 1 theme HA 671:672 arg1 incorporation 654:666 successful incorporation 643:666 successful incorporation of HA in the membranes 643:689 FTIR analysis indicated successful incorporation of HA in the membranes and XRD analysis showed that no changes in the HA crystalline structure were observed after incorporation. 36840027 8 2 theme stem 1100:1103 arg1 cells 1105:1109 dental pulp mesenchymal stem cells 1076:1109 dental pulp mesenchymal stem cells 1076:1109 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 8 3 located observed 1115:1122 arg2 Greater 1042:1048 Greater 1042:1048 Greater 1042:1048 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 8 3 located observed 1115:1122 arg1 surface 1131:1137 the surface 1127:1137 the surface of the membrane 1127:1153 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 2 4 used used 351:354 arg2 gum 338:340 xanthan gum 330:340 xanthan gum (X) 330:344 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 4 used used 351:354 arg2 polysaccharides 297:311 The mucoadhesive polysaccharides 280:311 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) 280:344 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 4 used used 351:354 arg2 chitosan 313:320 chitosan 313:320 chitosan (C) 313:324 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 1 5 theme dense 174:178 arg1 membranes 211:219 dense composite polysaccharide-based membranes 174:219 dense composite polysaccharide-based membranes 174:219 In this work, a simple method was proposed to produce dense composite polysaccharide-based membranes to be used for guided tissue and guided bone regeneration. 36840027 4 6 from incorporation 654:666 arg1 membranes 681:689 the membranes 677:689 the membranes 677:689 FTIR analysis indicated successful incorporation of HA in the membranes and XRD analysis showed that no changes in the HA crystalline structure were observed after incorporation. 36840027 10 7 from treatment 1516:1524 arg1 techniques 1497:1506 regenerative techniques 1484:1506 regenerative techniques 1484:1506 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 9 8 theme mechanical 1253:1262 arg1 properties 1279:1288 mechanical and biological properties 1253:1288 mechanical and biological properties 1253:1288 However, the 1:1:2 formulation showed the most adequate balance of mechanical and biological properties. 36840027 10 9 theme periodontal 1529:1539 arg1 lesions 1541:1547 periodontal lesions 1529:1547 periodontal lesions 1529:1547 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 3 10 theme equal 513:517 arg1 proportions 501:511 C:X:HA mass proportions 489:511 C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10 489:547 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 6 11 theme distinct 957:964 arg1 roughness 966:974 distinct roughness 957:974 distinct roughness 957:974 The membranes produced showed asymmetrical surfaces, with distinct roughness. 36840027 10 12 theme cell 1392:1395 arg1 adhesion 1397:1404 cell adhesion 1392:1404 cell adhesion 1392:1404 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 4 13 from changes 723:729 arg1 structure 753:761 the HA crystalline structure 734:761 the HA crystalline structure 734:761 FTIR analysis indicated successful incorporation of HA in the membranes and XRD analysis showed that no changes in the HA crystalline structure were observed after incorporation. 36840027 9 14 theme biological 1268:1277 arg1 properties 1279:1288 mechanical and biological properties 1253:1288 mechanical and biological properties 1253:1288 However, the 1:1:2 formulation showed the most adequate balance of mechanical and biological properties. 36840027 10 15 theme potential 1440:1448 arg1 application 1450:1460 the potential application 1436:1460 the potential application of these materials in regenerative techniques 1436:1506 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 5 16 theme residual 802:809 arg1 mass 811:814 The residual mass 798:814 The residual mass evaluated by TGA 798:831 The residual mass evaluated by TGA was higher for the formulation produced at the proportion 1:1:10. 36840027 5 16 theme residual 802:809 arg1 higher 837:842 higher 837:842 higher 837:842 The residual mass evaluated by TGA was higher for the formulation produced at the proportion 1:1:10. 36840027 1 17 theme composite 180:188 arg1 membranes 211:219 dense composite polysaccharide-based membranes 174:219 dense composite polysaccharide-based membranes 174:219 In this work, a simple method was proposed to produce dense composite polysaccharide-based membranes to be used for guided tissue and guided bone regeneration. 36840027 8 18 theme membrane 1146:1153 arg1 surface 1131:1137 the surface 1127:1137 the surface of the membrane 1127:1153 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 9 19 theme properties 1279:1288 arg1 balance 1242:1248 the most adequate balance 1224:1248 the most adequate balance of mechanical and biological properties 1224:1288 However, the 1:1:2 formulation showed the most adequate balance of mechanical and biological properties. 36840027 3 20 dep C 489:489 arg1 X 491:491 X 491:491 C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10 489:547 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 3 20 dep C 489:489 arg1 mass 496:499 HA mass 493:499 C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10 489:547 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 1 21 theme polysaccharide-based 190:209 arg1 membranes 211:219 dense composite polysaccharide-based membranes 174:219 dense composite polysaccharide-based membranes 174:219 In this work, a simple method was proposed to produce dense composite polysaccharide-based membranes to be used for guided tissue and guided bone regeneration. 36840027 0 22 theme Chitosan-Xanthan 14:29 arg1 Membranes 35:43 Cell-Friendly Chitosan-Xanthan Gum Membranes 0:43 Cell-Friendly Chitosan-Xanthan Gum Membranes Incorporating Hydroxyapatite 0:72 Cell-Friendly Chitosan-Xanthan Gum Membranes Incorporating Hydroxyapatite Designed for Periodontal Tissue Regeneration. 36840027 8 23 dep observed 1115:1122 arg1 proportion 1174:1183 X:HA proportion 1169:1183 X:HA proportion 1169:1183 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 0 24 theme Cell-Friendly 0:12 arg1 Membranes 35:43 Cell-Friendly Chitosan-Xanthan Gum Membranes 0:43 Cell-Friendly Chitosan-Xanthan Gum Membranes Incorporating Hydroxyapatite 0:72 Cell-Friendly Chitosan-Xanthan Gum Membranes Incorporating Hydroxyapatite Designed for Periodontal Tissue Regeneration. 36840027 8 25 theme in 1050:1051 arg1 proliferation 1059:1071 in vitro proliferation 1050:1071 Greater in vitro proliferation of dental pulp mesenchymal stem cells 1042:1109 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 2 26 theme xanthan 330:336 arg1 polysaccharides 297:311 The mucoadhesive polysaccharides 280:311 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) 280:344 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 26 theme xanthan 330:336 arg1 X 343:343 X 343:343 X 343:343 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 26 theme xanthan 330:336 arg1 gum 338:340 xanthan gum 330:340 xanthan gum (X) 330:344 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 27 theme complex 389:395 arg1 membranes 397:405 polyelectrolyte-based complex membranes 367:405 polyelectrolyte-based complex membranes 367:405 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 8 28 theme X 1169:1169 arg1 proportion 1174:1183 X:HA proportion 1169:1183 X:HA proportion 1169:1183 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 4 29 theme XRD 695:697 arg1 analysis 699:706 XRD analysis 695:706 XRD analysis 695:706 FTIR analysis indicated successful incorporation of HA in the membranes and XRD analysis showed that no changes in the HA crystalline structure were observed after incorporation. 36840027 10 30 theme materials 1471:1479 arg1 application 1450:1460 the potential application 1436:1460 the potential application of these materials in regenerative techniques 1436:1506 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 10 30 theme materials 1471:1479 arg1 treatment 1516:1524 the treatment 1512:1524 the treatment of periodontal lesions 1512:1547 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 10 31 theme lesions 1541:1547 arg1 application 1450:1460 the potential application 1436:1460 the potential application of these materials in regenerative techniques 1436:1506 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 10 31 theme lesions 1541:1547 arg1 treatment 1516:1524 the treatment 1512:1524 the treatment of periodontal lesions 1512:1547 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 10 32 theme mechanical 1359:1368 arg1 parameters 1370:1379 mechanical parameters 1359:1379 mechanical parameters as well as cell adhesion and proliferation 1359:1422 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 3 33 theme potential 462:470 arg1 carrier 477:483 a potential drug carrier 460:483 a potential drug carrier 460:483 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 0 34 theme Gum 31:33 arg1 Membranes 35:43 Cell-Friendly Chitosan-Xanthan Gum Membranes 0:43 Cell-Friendly Chitosan-Xanthan Gum Membranes Incorporating Hydroxyapatite 0:72 Cell-Friendly Chitosan-Xanthan Gum Membranes Incorporating Hydroxyapatite Designed for Periodontal Tissue Regeneration. 36840027 6 35 theme asymmetrical 929:940 arg1 surfaces 942:949 asymmetrical surfaces 929:949 asymmetrical surfaces 929:949 The membranes produced showed asymmetrical surfaces, with distinct roughness. 36840027 3 36 theme biomimetic 596:605 arg1 properties 607:616 biomimetic properties 596:616 biomimetic properties 596:616 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 3 37 theme drug 472:475 arg1 carrier 477:483 a potential drug carrier 460:483 a potential drug carrier 460:483 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 8 38 theme HA 1171:1172 arg1 proportion 1174:1183 X:HA proportion 1169:1183 X:HA proportion 1169:1183 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 3 39 theme C 489:489 arg1 proportions 501:511 C:X:HA mass proportions 489:511 C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10 489:547 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 8 40 theme pulp 1083:1086 arg1 cells 1105:1109 dental pulp mesenchymal stem cells 1076:1109 dental pulp mesenchymal stem cells 1076:1109 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 3 41 dep added 432:436 arg1 improve 562:568 improve 562:568 to improve membranes bioactivity and biomimetic properties 559:616 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 3 41 dep added 432:436 arg1 proportions 501:511 C:X:HA mass proportions 489:511 C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10 489:547 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 3 41 dep added 432:436 arg1 also 554:557 also 554:557 also 554:557 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 4 42 theme FTIR 619:622 arg1 analysis 624:631 FTIR analysis 619:631 FTIR analysis 619:631 FTIR analysis indicated successful incorporation of HA in the membranes and XRD analysis showed that no changes in the HA crystalline structure were observed after incorporation. 36840027 8 43 theme dental 1076:1081 arg1 cells 1105:1109 dental pulp mesenchymal stem cells 1076:1109 dental pulp mesenchymal stem cells 1076:1109 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 7 44 theme HA 992:993 arg1 concentration 995:1007 the HA concentration 988:1007 Increasing the HA concentration 977:1007 Increasing the HA concentration increased the surface roughness. 36840027 1 45 theme guided 236:241 arg1 tissue 243:248 guided tissue 236:248 guided tissue 236:248 In this work, a simple method was proposed to produce dense composite polysaccharide-based membranes to be used for guided tissue and guided bone regeneration. 36840027 7 46 theme surface 1023:1029 arg1 roughness 1031:1039 the surface roughness 1019:1039 the surface roughness 1019:1039 Increasing the HA concentration increased the surface roughness. 36840027 8 47 dep in 1050:1051 arg1 vitro 1053:1057 vitro 1053:1057 vitro 1053:1057 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 1 48 used used 227:230 arg2 method 143:148 a simple method 134:148 a simple method 134:148 In this work, a simple method was proposed to produce dense composite polysaccharide-based membranes to be used for guided tissue and guided bone regeneration. 36840027 8 49 theme mesenchymal 1088:1098 arg1 cells 1105:1109 dental pulp mesenchymal stem cells 1076:1109 dental pulp mesenchymal stem cells 1076:1109 Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. 36840027 9 50 theme 1:1:2 1199:1203 arg1 formulation 1205:1215 the 1:1:2 formulation 1195:1215 the 1:1:2 formulation 1195:1215 However, the 1:1:2 formulation showed the most adequate balance of mechanical and biological properties. 36840027 7 51 theme Increasing 977:986 arg1 concentration 995:1007 the HA concentration 988:1007 Increasing the HA concentration 977:1007 Increasing the HA concentration increased the surface roughness. 36840027 1 52 theme simple 136:141 arg1 method 143:148 a simple method 134:148 a simple method 134:148 In this work, a simple method was proposed to produce dense composite polysaccharide-based membranes to be used for guided tissue and guided bone regeneration. 36840027 10 53 theme regenerative 1484:1495 arg1 techniques 1497:1506 regenerative techniques 1484:1506 regenerative techniques 1484:1506 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 4 54 theme crystalline 741:751 arg1 structure 753:761 the HA crystalline structure 734:761 the HA crystalline structure 734:761 FTIR analysis indicated successful incorporation of HA in the membranes and XRD analysis showed that no changes in the HA crystalline structure were observed after incorporation. 36840027 2 55 theme mucoadhesive 284:295 arg1 polysaccharides 297:311 The mucoadhesive polysaccharides 280:311 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) 280:344 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 55 theme mucoadhesive 284:295 arg1 chitosan 313:320 chitosan 313:320 chitosan (C) 313:324 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 55 theme mucoadhesive 284:295 arg1 gum 338:340 xanthan gum 330:340 xanthan gum (X) 330:344 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 4 56 theme successful 643:652 arg1 incorporation 654:666 successful incorporation 643:666 successful incorporation of HA in the membranes 643:689 FTIR analysis indicated successful incorporation of HA in the membranes and XRD analysis showed that no changes in the HA crystalline structure were observed after incorporation. 36840027 5 57 theme proportion 880:889 arg1 1:1:10 891:896 the proportion 1:1:10 876:896 the proportion 1:1:10 876:896 The residual mass evaluated by TGA was higher for the formulation produced at the proportion 1:1:10. 36840027 4 58 theme HA 738:739 arg1 structure 753:761 the HA crystalline structure 734:761 the HA crystalline structure 734:761 FTIR analysis indicated successful incorporation of HA in the membranes and XRD analysis showed that no changes in the HA crystalline structure were observed after incorporation. 36840027 3 59 theme HA 493:494 arg1 mass 496:499 HA mass 493:499 C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10 489:547 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 10 60 from application 1450:1460 arg1 techniques 1497:1506 regenerative techniques 1484:1506 regenerative techniques 1484:1506 These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions. 36840027 0 61 theme Tissue 99:104 arg1 Regeneration 106:117 Periodontal Tissue Regeneration 87:117 Periodontal Tissue Regeneration 87:117 Cell-Friendly Chitosan-Xanthan Gum Membranes Incorporating Hydroxyapatite Designed for Periodontal Tissue Regeneration. 36840027 3 62 dep membranes 570:578 arg1 bioactivity 580:590 bioactivity 580:590 bioactivity 580:590 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 3 62 dep membranes 570:578 arg1 properties 607:616 biomimetic properties 596:616 biomimetic properties 596:616 Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. 36840027 2 63 theme polyelectrolyte-based 367:387 arg1 membranes 397:405 polyelectrolyte-based complex membranes 367:405 polyelectrolyte-based complex membranes 367:405 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 1 64 theme guided 254:259 arg1 regeneration 266:277 guided bone regeneration 254:277 guided bone regeneration 254:277 In this work, a simple method was proposed to produce dense composite polysaccharide-based membranes to be used for guided tissue and guided bone regeneration. 36840027 0 65 theme Periodontal 87:97 arg1 Regeneration 106:117 Periodontal Tissue Regeneration 87:117 Periodontal Tissue Regeneration 87:117 Cell-Friendly Chitosan-Xanthan Gum Membranes Incorporating Hydroxyapatite Designed for Periodontal Tissue Regeneration. 36840027 9 66 theme adequate 1233:1240 arg1 balance 1242:1248 the most adequate balance 1224:1248 the most adequate balance of mechanical and biological properties 1224:1288 However, the 1:1:2 formulation showed the most adequate balance of mechanical and biological properties. 36840027 2 67 dep polysaccharides 297:311 arg1 polysaccharides 297:311 The mucoadhesive polysaccharides 280:311 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) 280:344 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 67 dep polysaccharides 297:311 arg1 X 343:343 X 343:343 X 343:343 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 67 dep polysaccharides 297:311 arg1 C 323:323 C 323:323 C 323:323 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 67 dep polysaccharides 297:311 arg1 chitosan 313:320 chitosan 313:320 chitosan (C) 313:324 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 2 67 dep polysaccharides 297:311 arg1 gum 338:340 xanthan gum 330:340 xanthan gum (X) 330:344 The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. 36840027 1 68 theme bone 261:264 arg1 regeneration 266:277 guided bone regeneration 254:277 guided bone regeneration 254:277 In this work, a simple method was proposed to produce dense composite polysaccharide-based membranes to be used for guided tissue and guided bone regeneration. 35467318 5 0 theme metagenomic 664:674 arg1 analysis 703:710 The metagenomic and untargeted metabolomic analysis 660:710 The metagenomic and untargeted metabolomic analysis 660:710 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 8 1 theme Bacteroides 1420:1430 arg1 markers 1502:1508 microbial markers 1492:1508 microbial markers of physiological post-weaning diarrhea in piglets 1492:1558 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 8 1 theme Bacteroides 1420:1430 arg1 abundance 1407:1415 the lower abundance 1397:1415 the lower abundance of Bacteroides and its associated metabolic dysfunction 1397:1471 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 8 2 from markers 1502:1508 arg1 piglets 1552:1558 piglets 1552:1558 piglets 1552:1558 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 3 3 theme current 324:330 arg1 study 332:336 the current study 320:336 the current study 320:336 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 5 4 theme untargeted 680:689 arg1 analysis 703:710 The metagenomic and untargeted metabolomic analysis 660:710 The metagenomic and untargeted metabolomic analysis 660:710 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 3 5 theme group 488:492 arg1 diarrhea 478:485 post-weaning diarrhea 465:485 post-weaning diarrhea (group D, n=7) 465:500 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 3 5 theme group 488:492 arg1 D 494:494 group D 488:494 group D 488:494 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 6 6 theme carbohydrates 1075:1087 arg1 metabolism 962:971 The carbohydrate metabolism 945:971 The carbohydrate metabolism 945:971 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 6 theme carbohydrates 1075:1087 arg1 metabolism 1009:1018 lipid metabolism 1003:1018 lipid metabolism 1003:1018 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 6 theme carbohydrates 1075:1087 arg1 biosynthesis 974:985 biosynthesis 974:985 biosynthesis 974:985 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 6 theme carbohydrates 1075:1087 arg1 activity 1052:1059 the activity 1048:1059 the activity of glycan and carbohydrates digestion related enzymes 1048:1113 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 6 theme carbohydrates 1075:1087 arg1 metabolism 991:1000 metabolism 991:1000 metabolism 991:1000 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 6 theme carbohydrates 1075:1087 arg1 metabolism 1032:1041 amino acid metabolism 1021:1041 amino acid metabolism 1021:1041 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 7 7 theme microbiota 1244:1253 arg1 profiles 1226:1233 the metabolic profiles 1212:1233 the metabolic profiles of fecal microbiota 1212:1253 Diarrhea significantly changed the metabolic profiles of fecal microbiota, and most of the altered metabolites were negatively or positively correlated with the change in the abundance of Bacteroides. 35467318 4 8 theme H 606:606 arg1 piglets 614:620 H and D piglets 606:620 H and D piglets (weaned at 21 d and sampled at 26 d) 606:657 Each of 7 fecal samples was collected from H and D piglets (weaned at 21 d and sampled at 26 d). 35467318 0 9 theme post-weaning 88:99 arg1 diarrhea 101:108 the post-weaning diarrhea 84:108 the post-weaning diarrhea in piglets 84:119 Lower abundance of Bacteroides and metabolic dysfunction are highly associated with the post-weaning diarrhea in piglets. 35467318 8 10 theme dysfunction 1461:1471 arg1 markers 1502:1508 microbial markers 1492:1508 microbial markers of physiological post-weaning diarrhea in piglets 1492:1558 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 8 10 theme dysfunction 1461:1471 arg1 abundance 1407:1415 the lower abundance 1397:1415 the lower abundance of Bacteroides and its associated metabolic dysfunction 1397:1471 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 5 11 dep abundance 843:851 arg1 the 831:833 the 831:833 the 831:833 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 2 12 theme post-weaning 278:289 arg1 diarrhea 291:298 post-weaning diarrhea 278:298 post-weaning diarrhea 278:298 However, whether there are microbial markers associated with post-weaning diarrhea remains unknown. 35467318 8 13 theme post-weaning 1527:1538 arg1 diarrhea 1540:1547 physiological post-weaning diarrhea 1513:1547 physiological post-weaning diarrhea in piglets 1513:1558 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 5 14 from composition 740:750 arg1 pigs 789:792 D pigs 787:792 D pigs 787:792 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 8 15 from diarrhea 1540:1547 arg1 piglets 1552:1558 piglets 1552:1558 piglets 1552:1558 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 4 16 theme fecal 573:577 arg1 samples 579:585 7 fecal samples 571:585 7 fecal samples 571:585 Each of 7 fecal samples was collected from H and D piglets (weaned at 21 d and sampled at 26 d). 35467318 6 17 theme digestion 1089:1097 arg1 enzymes 1107:1113 digestion related enzymes 1089:1113 digestion related enzymes 1089:1113 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 5 18 theme D 787:787 arg1 pigs 789:792 D pigs 787:792 D pigs 787:792 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 3 19 theme group 434:438 arg1 n=7 443:445 group H, n=7 434:445 n=7 443:445 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 3 19 theme group 434:438 arg1 piglets 425:431 healthy weaned piglets 410:431 healthy weaned piglets (group H, n=7) 410:446 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 0 20 theme metabolic 35:43 arg1 dysfunction 45:55 metabolic dysfunction 35:55 metabolic dysfunction 35:55 Lower abundance of Bacteroides and metabolic dysfunction are highly associated with the post-weaning diarrhea in piglets. 35467318 4 21 dep piglets 614:620 arg1 weaned 623:628 weaned 623:628 weaned at 21 d 623:636 Each of 7 fecal samples was collected from H and D piglets (weaned at 21 d and sampled at 26 d). 35467318 4 21 dep piglets 614:620 arg1 sampled 642:648 sampled 642:648 sampled at 26 d 642:656 Each of 7 fecal samples was collected from H and D piglets (weaned at 21 d and sampled at 26 d). 35467318 3 22 theme H 440:440 arg1 n=7 443:445 group H, n=7 434:445 n=7 443:445 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 3 22 theme H 440:440 arg1 piglets 425:431 healthy weaned piglets 410:431 healthy weaned piglets (group H, n=7) 410:446 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 8 23 theme microbial 1492:1500 arg1 markers 1502:1508 microbial markers 1492:1508 microbial markers of physiological post-weaning diarrhea in piglets 1492:1558 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 8 23 theme microbial 1492:1500 arg1 abundance 1407:1415 the lower abundance 1397:1415 the lower abundance of Bacteroides and its associated metabolic dysfunction 1397:1471 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 6 24 theme lipid 1003:1007 arg1 metabolism 1009:1018 lipid metabolism 1003:1018 lipid metabolism 1003:1018 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 8 25 theme metabolic 1451:1459 arg1 dysfunction 1461:1471 its associated metabolic dysfunction 1436:1471 its associated metabolic dysfunction 1436:1471 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 4 26 theme D 612:612 arg1 piglets 614:620 H and D piglets 606:620 H and D piglets (weaned at 21 d and sampled at 26 d) 606:657 Each of 7 fecal samples was collected from H and D piglets (weaned at 21 d and sampled at 26 d). 35467318 0 27 theme Lower 0:4 arg1 abundance 6:14 Lower abundance 0:14 Lower abundance of Bacteroides 0:29 Lower abundance of Bacteroides and metabolic dysfunction are highly associated with the post-weaning diarrhea in piglets. 35467318 6 28 theme H 1173:1173 arg1 pigs 1175:1178 H pigs 1173:1178 H pigs 1173:1178 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 29 theme glycan 1064:1069 arg1 metabolism 962:971 The carbohydrate metabolism 945:971 The carbohydrate metabolism 945:971 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 29 theme glycan 1064:1069 arg1 metabolism 1009:1018 lipid metabolism 1003:1018 lipid metabolism 1003:1018 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 29 theme glycan 1064:1069 arg1 biosynthesis 974:985 biosynthesis 974:985 biosynthesis 974:985 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 29 theme glycan 1064:1069 arg1 activity 1052:1059 the activity 1048:1059 the activity of glycan and carbohydrates digestion related enzymes 1048:1113 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 29 theme glycan 1064:1069 arg1 metabolism 991:1000 metabolism 991:1000 metabolism 991:1000 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 29 theme glycan 1064:1069 arg1 metabolism 1032:1041 amino acid metabolism 1021:1041 amino acid metabolism 1021:1041 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 6 30 dep glycan 1064:1069 arg1 enzymes 1107:1113 digestion related enzymes 1089:1113 digestion related enzymes 1089:1113 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 0 31 theme Bacteroides 19:29 arg1 dysfunction 45:55 metabolic dysfunction 35:55 metabolic dysfunction 35:55 Lower abundance of Bacteroides and metabolic dysfunction are highly associated with the post-weaning diarrhea in piglets. 35467318 0 31 theme Bacteroides 19:29 arg1 abundance 6:14 Lower abundance 0:14 Lower abundance of Bacteroides 0:29 Lower abundance of Bacteroides and metabolic dysfunction are highly associated with the post-weaning diarrhea in piglets. 35467318 6 32 theme D 1152:1152 arg1 pigs 1154:1157 D pigs 1152:1157 D pigs 1152:1157 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 3 33 dep D 494:494 arg1 n=7 497:499 n=7 497:499 n=7 497:499 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 1 34 theme gut 193:195 arg1 microbiota 197:206 gut microbiota 193:206 gut microbiota in pigs 193:214 Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. 35467318 5 35 theme Bacteroides 867:877 arg1 number 857:862 number 857:862 number 857:862 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 5 35 theme Bacteroides 867:877 arg1 abundance 843:851 reduced abundance 835:851 reduced abundance 835:851 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 1 36 theme microbiota 197:206 arg1 disorders 180:188 disorders 180:188 disorders of gut microbiota in pigs 180:214 Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. 35467318 1 36 theme microbiota 197:206 arg1 diarrhea 167:174 diarrhea 167:174 diarrhea 167:174 Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. 35467318 3 37 theme healthy 410:416 arg1 n=7 443:445 group H, n=7 434:445 n=7 443:445 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 3 37 theme healthy 410:416 arg1 piglets 425:431 healthy weaned piglets 410:431 healthy weaned piglets (group H, n=7) 410:446 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 6 38 dep showed 1115:1120 arg1 down-regulated 1134:1147 down-regulated 1134:1147 showed extensively down-regulated in D pigs compared with H pigs 1115:1178 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 8 39 from piglets 1552:1558 arg1 markers 1502:1508 microbial markers 1492:1508 microbial markers of physiological post-weaning diarrhea in piglets 1492:1558 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 8 39 from piglets 1552:1558 arg1 abundance 1407:1415 the lower abundance 1397:1415 the lower abundance of Bacteroides and its associated metabolic dysfunction 1397:1471 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 3 40 theme microbial 544:552 arg1 markers 554:560 diarrhea associated microbial markers 524:560 diarrhea associated microbial markers 524:560 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 8 41 theme diarrhea 1540:1547 arg1 markers 1502:1508 microbial markers 1492:1508 microbial markers of physiological post-weaning diarrhea in piglets 1492:1558 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 8 41 theme diarrhea 1540:1547 arg1 abundance 1407:1415 the lower abundance 1397:1415 the lower abundance of Bacteroides and its associated metabolic dysfunction 1397:1471 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 7 42 theme Bacteroides 1369:1379 arg1 abundance 1356:1364 the abundance 1352:1364 the abundance of Bacteroides 1352:1379 Diarrhea significantly changed the metabolic profiles of fecal microbiota, and most of the altered metabolites were negatively or positively correlated with the change in the abundance of Bacteroides. 35467318 3 43 theme weaned 418:423 arg1 n=7 443:445 group H, n=7 434:445 n=7 443:445 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 3 43 theme weaned 418:423 arg1 piglets 425:431 healthy weaned piglets 410:431 healthy weaned piglets (group H, n=7) 410:446 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 8 44 theme physiological 1513:1525 arg1 diarrhea 1540:1547 physiological post-weaning diarrhea 1513:1547 physiological post-weaning diarrhea in piglets 1513:1558 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 5 45 theme metabolomic 691:701 arg1 analysis 703:710 The metagenomic and untargeted metabolomic analysis 660:710 The metagenomic and untargeted metabolomic analysis 660:710 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 5 46 theme host 939:942 arg1 status 929:934 the diarrhea status 916:934 the diarrhea status of host 916:942 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 5 47 theme microbial 730:738 arg1 composition 740:750 the microbial composition 726:750 the microbial composition 726:750 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 6 48 theme carbohydrate 949:960 arg1 metabolism 962:971 The carbohydrate metabolism 945:971 The carbohydrate metabolism 945:971 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 1 49 from pigs 211:214 arg1 disorders 180:188 disorders 180:188 disorders of gut microbiota in pigs 180:214 Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. 35467318 1 49 from pigs 211:214 arg1 diarrhea 167:174 diarrhea 167:174 diarrhea 167:174 Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. 35467318 3 50 theme post-weaning 465:476 arg1 diarrhea 478:485 post-weaning diarrhea 465:485 post-weaning diarrhea (group D, n=7) 465:500 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 3 50 theme post-weaning 465:476 arg1 D 494:494 group D 488:494 group D 488:494 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 6 51 theme related 1099:1105 arg1 enzymes 1107:1113 digestion related enzymes 1089:1113 digestion related enzymes 1089:1113 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 8 52 theme lower 1401:1405 arg1 markers 1502:1508 microbial markers 1492:1508 microbial markers of physiological post-weaning diarrhea in piglets 1492:1558 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 8 52 theme lower 1401:1405 arg1 abundance 1407:1415 the lower abundance 1397:1415 the lower abundance of Bacteroides and its associated metabolic dysfunction 1397:1471 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 3 53 theme associated 533:542 arg1 markers 554:560 diarrhea associated microbial markers 524:560 diarrhea associated microbial markers 524:560 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 1 54 theme Growing 122:128 arg1 evidences 130:138 Growing evidences 122:138 Growing evidences 122:138 Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. 35467318 7 55 theme altered 1272:1278 arg1 metabolites 1280:1290 the altered metabolites 1268:1290 the altered metabolites 1268:1290 Diarrhea significantly changed the metabolic profiles of fecal microbiota, and most of the altered metabolites were negatively or positively correlated with the change in the abundance of Bacteroides. 35467318 1 56 from microbiota 197:206 arg1 pigs 211:214 pigs 211:214 pigs 211:214 Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. 35467318 5 57 theme reduced 835:841 arg1 abundance 843:851 reduced abundance 835:851 reduced abundance 835:851 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 5 58 from profile 776:782 arg1 pigs 789:792 D pigs 787:792 D pigs 787:792 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 5 59 from function 753:760 arg1 pigs 789:792 D pigs 787:792 D pigs 787:792 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 0 60 from diarrhea 101:108 arg1 piglets 113:119 piglets 113:119 piglets 113:119 Lower abundance of Bacteroides and metabolic dysfunction are highly associated with the post-weaning diarrhea in piglets. 35467318 2 61 theme microbial 244:252 arg1 markers 254:260 microbial markers 244:260 microbial markers associated with post-weaning diarrhea 244:298 However, whether there are microbial markers associated with post-weaning diarrhea remains unknown. 35467318 1 62 from disorders 180:188 arg1 pigs 211:214 pigs 211:214 pigs 211:214 Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. 35467318 6 63 theme amino 1021:1025 arg1 metabolism 1032:1041 amino acid metabolism 1021:1041 amino acid metabolism 1021:1041 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 7 64 from change 1342:1347 arg1 abundance 1356:1364 the abundance 1352:1364 the abundance of Bacteroides 1352:1379 Diarrhea significantly changed the metabolic profiles of fecal microbiota, and most of the altered metabolites were negatively or positively correlated with the change in the abundance of Bacteroides. 35467318 8 65 theme associated 1440:1449 arg1 dysfunction 1461:1471 its associated metabolic dysfunction 1436:1471 its associated metabolic dysfunction 1436:1471 In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets. 35467318 5 66 theme metabolic 766:774 arg1 profile 776:782 metabolic profile 766:782 metabolic profile 766:782 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 5 67 theme diarrhea 920:927 arg1 status 929:934 the diarrhea status 916:934 the diarrhea status of host 916:942 The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. 35467318 7 68 theme fecal 1238:1242 arg1 microbiota 1244:1253 fecal microbiota 1238:1253 fecal microbiota 1238:1253 Diarrhea significantly changed the metabolic profiles of fecal microbiota, and most of the altered metabolites were negatively or positively correlated with the change in the abundance of Bacteroides. 35467318 6 69 theme acid 1027:1030 arg1 metabolism 1032:1041 amino acid metabolism 1021:1041 amino acid metabolism 1021:1041 The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. 35467318 3 70 dep associated 533:542 arg1 diarrhea 524:531 diarrhea 524:531 diarrhea 524:531 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 35467318 7 71 theme metabolic 1216:1224 arg1 profiles 1226:1233 the metabolic profiles 1212:1233 the metabolic profiles of fecal microbiota 1212:1253 Diarrhea significantly changed the metabolic profiles of fecal microbiota, and most of the altered metabolites were negatively or positively correlated with the change in the abundance of Bacteroides. 35467318 1 72 from diarrhea 167:174 arg1 pigs 211:214 pigs 211:214 pigs 211:214 Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. 35467318 1 73 theme direct 147:152 arg1 link 154:157 a direct link 145:157 a direct link between diarrhea and disorders of gut microbiota in pigs 145:214 Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. 35467318 3 74 theme microbial 355:363 arg1 community 365:373 the microbial community 351:373 the microbial community 351:373 In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. 36865097 6 0 theme second 995:1000 arg1 step 1002:1005 the second step 991:1005 the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor 991:1129 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 12 1 theme prior 1889:1893 arg1 steps 1895:1899 prior steps 1889:1899 prior steps 1889:1899 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 10 2 theme biofilm 1585:1591 arg1 macromolecules 1600:1613 the biofilm matrix macromolecules 1581:1613 the biofilm matrix macromolecules 1581:1613 Key to our ability to systematically promote or ablate biofilm formation is a detailed understanding of the biofilm matrix macromolecules. 36865097 11 3 theme biofilm 1688:1694 arg1 pathway 1731:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 Here we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway. 36865097 3 4 theme first 535:539 arg1 steps 564:568 the first two membrane-committed steps 531:568 the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway 531:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 12 5 theme steps 1842:1846 arg1 characterization 1818:1833 the sequential characterization 1803:1833 the sequential characterization of the steps in exopolysaccharide biosynthesis 1803:1880 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 7 6 theme first 1160:1164 arg1 monosaccharides 1170:1184 the first two monosaccharides 1156:1184 the first two monosaccharides 1156:1184 Thus, the study defines the first two monosaccharides at the reducing end of the growing exopolysaccharide unit. 36865097 3 7 theme exopolysaccharide 577:593 arg1 pathway 608:614 the exopolysaccharide biosynthetic pathway 573:614 the exopolysaccharide biosynthetic pathway 573:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 1 8 dep Bacillus 62:69 arg1 subtilis 71:78 subtilis 71:78 subtilis 71:78 The Bacillus subtilis extracellular biofilm matrix includes an exopolysaccharide that is critical for the architecture and function of the community. 36865097 12 9 theme exopolysaccharide 1851:1867 arg1 biosynthesis 1869:1880 exopolysaccharide biosynthesis 1851:1880 exopolysaccharide biosynthesis 1851:1880 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 7 10 theme exopolysaccharide 1221:1237 arg1 unit 1239:1242 the growing exopolysaccharide unit 1209:1242 the growing exopolysaccharide unit 1209:1242 Thus, the study defines the first two monosaccharides at the reducing end of the growing exopolysaccharide unit. 36865097 6 11 theme fold 948:951 arg1 transferase 962:972 a GT-B fold glycosyl transferase 941:972 a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor 941:1129 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 6 11 theme fold 948:951 arg1 EpsD 933:936 EpsD 933:936 EpsD 933:936 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 12 12 theme sequential 1807:1816 arg1 characterization 1818:1833 the sequential characterization 1803:1833 the sequential characterization of the steps in exopolysaccharide biosynthesis 1803:1880 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 7 13 theme growing 1213:1219 arg1 unit 1239:1242 the growing exopolysaccharide unit 1209:1242 the growing exopolysaccharide unit 1209:1242 Thus, the study defines the first two monosaccharides at the reducing end of the growing exopolysaccharide unit. 36865097 3 14 from activities 517:526 arg1 pathway 608:614 the exopolysaccharide biosynthetic pathway 573:614 the exopolysaccharide biosynthetic pathway 573:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 4 15 theme exopolysaccharide 773:789 arg1 pathway 804:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 5 16 theme phospho-sugar 912:924 arg1 donor 926:930 phospho-sugar donor 912:930 phospho-sugar donor 912:930 EpsL catalyzes the first phosphoglycosyl transferase step using UDP-di- N -acetyl bacillosamine as phospho-sugar donor. 36865097 12 17 from steps 1842:1846 arg1 biosynthesis 1869:1880 exopolysaccharide biosynthesis 1851:1880 exopolysaccharide biosynthesis 1851:1880 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 4 18 theme lipid-linked 687:698 arg1 substrates 709:718 lipid-linked acceptor substrates 687:718 lipid-linked acceptor substrates 687:718 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 11 19 from steps 1657:1661 arg1 pathway 1731:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 Here we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway. 36865097 4 20 theme B. 753:754 arg1 pathway 804:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 8 21 from evidence 1278:1285 arg1 exopolysaccharide 1326:1342 an exopolysaccharide 1323:1342 an exopolysaccharide synthesized by a Gram-positive bacterium 1323:1383 In doing so we provide the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium. 36865097 4 22 link lipid-linked 687:698 arg1 substrates 709:718 lipid-linked acceptor substrates 687:718 lipid-linked acceptor substrates 687:718 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 4 23 theme biofilm 765:771 arg1 pathway 804:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 3 24 from pathway 608:614 arg1 activities 517:526 the activities 513:526 the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway 513:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 2 25 theme machinery 255:263 arg1 understanding 221:233 our understanding 217:233 our understanding of the biosynthetic machinery 217:263 To date, our understanding of the biosynthetic machinery and the molecular composition of the exopolysaccharide of B. subtilis remains unclear and incomplete. 36865097 2 25 theme machinery 255:263 arg1 composition 283:293 the molecular composition 269:293 the molecular composition of the exopolysaccharide of B. subtilis 269:333 To date, our understanding of the biosynthetic machinery and the molecular composition of the exopolysaccharide of B. subtilis remains unclear and incomplete. 36865097 6 26 theme UDP- 1085:1088 arg1 glucosamine 1100:1110 UDP- N -acetyl glucosamine 1085:1110 UDP- N -acetyl glucosamine 1085:1110 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 8 27 theme Gram-positive 1361:1373 arg1 bacterium 1375:1383 a Gram-positive bacterium 1359:1383 a Gram-positive bacterium 1359:1383 In doing so we provide the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium. 36865097 0 28 from Steps 15:19 arg1 Biosynthesis 44:55 B. subtilis Biofilm Biosynthesis 24:55 B. subtilis Biofilm Biosynthesis 24:55 Defining Early Steps in B. subtilis Biofilm Biosynthesis. 36865097 5 29 theme first 832:836 arg1 step 866:869 the first phosphoglycosyl transferase step 828:869 the first phosphoglycosyl transferase step using UDP-di- N -acetyl bacillosamine as phospho-sugar donor 828:930 EpsL catalyzes the first phosphoglycosyl transferase step using UDP-di- N -acetyl bacillosamine as phospho-sugar donor. 36865097 8 30 from exopolysaccharide 1326:1342 arg1 evidence 1278:1285 the first evidence 1268:1285 the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium 1268:1383 In doing so we provide the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium. 36865097 6 31 theme EpsL 1051:1054 arg1 donor 1125:1129 the sugar donor 1115:1129 the sugar donor 1115:1129 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 6 31 theme EpsL 1051:1054 arg1 product 1040:1046 the product 1036:1046 the product of EpsL 1036:1054 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 6 31 theme EpsL 1051:1054 arg1 substrate 1071:1079 an acceptor substrate 1059:1079 an acceptor substrate 1059:1079 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 5 32 theme phosphoglycosyl 838:852 arg1 step 866:869 the first phosphoglycosyl transferase step 828:869 the first phosphoglycosyl transferase step using UDP-di- N -acetyl bacillosamine as phospho-sugar donor 828:930 EpsL catalyzes the first phosphoglycosyl transferase step using UDP-di- N -acetyl bacillosamine as phospho-sugar donor. 36865097 3 33 theme biochemical 400:410 arg1 studies 424:430 synergistic biochemical and genetic studies 388:430 synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway 388:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 4 34 theme biosynthetic 791:802 arg1 pathway 804:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 5 35 theme N 885:885 arg1 bacillosamine 895:907 UDP-di- N -acetyl bacillosamine 877:907 UDP-di- N -acetyl bacillosamine 877:907 EpsL catalyzes the first phosphoglycosyl transferase step using UDP-di- N -acetyl bacillosamine as phospho-sugar donor. 36865097 9 36 theme IMPORTANCE 1386:1395 arg1 way 1423:1425 the communal way 1410:1425 the communal way of life that microbes adopt to increase survival 1410:1474 IMPORTANCE Biofilms are the communal way of life that microbes adopt to increase survival. 36865097 9 36 theme IMPORTANCE 1386:1395 arg1 Biofilms 1397:1404 IMPORTANCE Biofilms 1386:1404 IMPORTANCE Biofilms 1386:1404 IMPORTANCE Biofilms are the communal way of life that microbes adopt to increase survival. 36865097 1 37 theme biofilm 94:100 arg1 matrix 102:107 The Bacillus subtilis extracellular biofilm matrix 58:107 The Bacillus subtilis extracellular biofilm matrix 58:107 The Bacillus subtilis extracellular biofilm matrix includes an exopolysaccharide that is critical for the architecture and function of the community. 36865097 6 38 theme sugar 1119:1123 arg1 donor 1125:1129 the sugar donor 1115:1129 the sugar donor 1115:1129 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 6 38 theme sugar 1119:1123 arg1 product 1040:1046 the product 1036:1046 the product of EpsL 1036:1054 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 2 39 theme molecular 273:281 arg1 composition 283:293 the molecular composition 269:293 the molecular composition of the exopolysaccharide of B. subtilis 269:333 To date, our understanding of the biosynthetic machinery and the molecular composition of the exopolysaccharide of B. subtilis remains unclear and incomplete. 36865097 6 40 theme GT-B 943:946 arg1 transferase 962:972 a GT-B fold glycosyl transferase 941:972 a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor 941:1129 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 6 40 theme GT-B 943:946 arg1 EpsD 933:936 EpsD 933:936 EpsD 933:936 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 3 41 theme sequence 471:478 arg1 analyses 480:487 comparative sequence analyses 459:487 comparative sequence analyses 459:487 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 0 42 theme B. 24:25 arg1 Biosynthesis 44:55 B. subtilis Biofilm Biosynthesis 24:55 B. subtilis Biofilm Biosynthesis 24:55 Defining Early Steps in B. subtilis Biofilm Biosynthesis. 36865097 9 43 theme communal 1414:1421 arg1 way 1423:1425 the communal way 1410:1425 the communal way of life that microbes adopt to increase survival 1410:1474 IMPORTANCE Biofilms are the communal way of life that microbes adopt to increase survival. 36865097 9 43 theme communal 1414:1421 arg1 Biofilms 1397:1404 IMPORTANCE Biofilms 1386:1404 IMPORTANCE Biofilms 1386:1404 IMPORTANCE Biofilms are the communal way of life that microbes adopt to increase survival. 36865097 5 44 theme transferase 854:864 arg1 step 866:869 the first phosphoglycosyl transferase step 828:869 the first phosphoglycosyl transferase step using UDP-di- N -acetyl bacillosamine as phospho-sugar donor 828:930 EpsL catalyzes the first phosphoglycosyl transferase step using UDP-di- N -acetyl bacillosamine as phospho-sugar donor. 36865097 6 45 theme -acetyl 1092:1098 arg1 glucosamine 1100:1110 UDP- N -acetyl glucosamine 1085:1110 UDP- N -acetyl glucosamine 1085:1110 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 3 46 theme genetic 416:422 arg1 studies 424:430 synergistic biochemical and genetic studies 388:430 synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway 388:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 0 47 theme Biofilm 36:42 arg1 Biosynthesis 44:55 B. subtilis Biofilm Biosynthesis 24:55 B. subtilis Biofilm Biosynthesis 24:55 Defining Early Steps in B. subtilis Biofilm Biosynthesis. 36865097 0 48 dep B. 24:25 arg1 subtilis 27:34 subtilis 27:34 subtilis 27:34 Defining Early Steps in B. subtilis Biofilm Biosynthesis. 36865097 12 49 theme undecaprenol 1943:1954 arg1 substrates 1982:1991 the undecaprenol diphosphate-linked glycan substrates 1939:1991 the undecaprenol diphosphate-linked glycan substrates 1939:1991 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 4 50 theme acceptor 700:707 arg1 substrates 709:718 lipid-linked acceptor substrates 687:718 lipid-linked acceptor substrates 687:718 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 6 51 from step 1002:1005 arg1 pathway 1014:1020 the pathway 1010:1020 the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor 1010:1129 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 11 52 theme synthesis 1721:1729 arg1 pathway 1731:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 Here we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway. 36865097 4 53 from enzymes 738:744 arg1 pathway 804:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 11 54 theme matrix 1696:1701 arg1 pathway 1731:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 Here we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway. 36865097 8 55 attach presence 1294:1301 arg2 bacillosamine 1306:1318 bacillosamine 1306:1318 bacillosamine 1306:1318 In doing so we provide the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium. 36865097 8 55 attach presence 1294:1301 arg1 exopolysaccharide 1326:1342 an exopolysaccharide 1323:1342 an exopolysaccharide synthesized by a Gram-positive bacterium 1323:1383 In doing so we provide the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium. 36865097 3 56 theme steps 564:568 arg1 activities 517:526 the activities 513:526 the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway 513:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 6 57 theme glycosyl 953:960 arg1 transferase 962:972 a GT-B fold glycosyl transferase 941:972 a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor 941:1129 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 6 57 theme glycosyl 953:960 arg1 EpsD 933:936 EpsD 933:936 EpsD 933:936 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 8 58 theme first 1272:1276 arg1 evidence 1278:1285 the first evidence 1268:1285 the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium 1268:1383 In doing so we provide the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium. 36865097 2 59 theme exopolysaccharide 302:318 arg1 understanding 221:233 our understanding 217:233 our understanding of the biosynthetic machinery 217:263 To date, our understanding of the biosynthetic machinery and the molecular composition of the exopolysaccharide of B. subtilis remains unclear and incomplete. 36865097 2 59 theme exopolysaccharide 302:318 arg1 composition 283:293 the molecular composition 269:293 the molecular composition of the exopolysaccharide of B. subtilis 269:333 To date, our understanding of the biosynthetic machinery and the molecular composition of the exopolysaccharide of B. subtilis remains unclear and incomplete. 36865097 1 60 theme community 197:205 arg1 function 181:188 function 181:188 function 181:188 The Bacillus subtilis extracellular biofilm matrix includes an exopolysaccharide that is critical for the architecture and function of the community. 36865097 1 60 theme community 197:205 arg1 architecture 164:175 architecture 164:175 architecture 164:175 The Bacillus subtilis extracellular biofilm matrix includes an exopolysaccharide that is critical for the architecture and function of the community. 36865097 11 61 dep Bacillus 1670:1677 arg1 subtilis 1679:1686 subtilis 1679:1686 subtilis 1679:1686 Here we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway. 36865097 8 62 theme presence 1294:1301 arg1 evidence 1278:1285 the first evidence 1268:1285 the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium 1268:1383 In doing so we provide the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium. 36865097 8 63 theme bacillosamine 1306:1318 arg1 presence 1294:1301 the presence 1290:1301 the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium 1290:1383 In doing so we provide the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium. 36865097 3 64 theme biosynthetic 595:606 arg1 pathway 608:614 the exopolysaccharide biosynthetic pathway 573:614 the exopolysaccharide biosynthetic pathway 573:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 6 65 theme N 1090:1090 arg1 glucosamine 1100:1110 UDP- N -acetyl glucosamine 1085:1110 UDP- N -acetyl glucosamine 1085:1110 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 4 66 theme subtilis 756:763 arg1 pathway 804:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 the B. subtilis biofilm exopolysaccharide biosynthetic pathway 749:810 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 2 67 theme biosynthetic 242:253 arg1 machinery 255:263 the biosynthetic machinery 238:263 the biosynthetic machinery 238:263 To date, our understanding of the biosynthetic machinery and the molecular composition of the exopolysaccharide of B. subtilis remains unclear and incomplete. 36865097 4 68 theme first 728:732 arg1 enzymes 738:744 the first two enzymes 724:744 the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway 724:810 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 3 69 from steps 564:568 arg1 pathway 608:614 the exopolysaccharide biosynthetic pathway 573:614 the exopolysaccharide biosynthetic pathway 573:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 8 70 from presence 1294:1301 arg1 exopolysaccharide 1326:1342 an exopolysaccharide 1323:1342 an exopolysaccharide synthesized by a Gram-positive bacterium 1323:1383 In doing so we provide the first evidence of the presence of bacillosamine in an exopolysaccharide synthesized by a Gram-positive bacterium. 36865097 6 71 theme acceptor 1062:1069 arg1 product 1040:1046 the product 1036:1046 the product of EpsL 1036:1054 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 6 71 theme acceptor 1062:1069 arg1 substrate 1071:1079 an acceptor substrate 1059:1079 an acceptor substrate 1059:1079 EpsD is a GT-B fold glycosyl transferase that facilitates the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP- N -acetyl glucosamine as the sugar donor. 36865097 12 72 theme glycan 1975:1980 arg1 substrates 1982:1991 the undecaprenol diphosphate-linked glycan substrates 1939:1991 the undecaprenol diphosphate-linked glycan substrates 1939:1991 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 2 73 theme subtilis 326:333 arg1 exopolysaccharide 302:318 the exopolysaccharide 298:318 the exopolysaccharide of B. subtilis 298:333 To date, our understanding of the biosynthetic machinery and the molecular composition of the exopolysaccharide of B. subtilis remains unclear and incomplete. 36865097 7 74 theme unit 1239:1242 arg1 end 1202:1204 the reducing end 1189:1204 the reducing end of the growing exopolysaccharide unit 1189:1242 Thus, the study defines the first two monosaccharides at the reducing end of the growing exopolysaccharide unit. 36865097 4 75 theme sugar 671:675 arg1 donor 677:681 the nucleotide sugar donor 656:681 the nucleotide sugar donor 656:681 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 1 76 theme Bacillus 62:69 arg1 matrix 102:107 The Bacillus subtilis extracellular biofilm matrix 58:107 The Bacillus subtilis extracellular biofilm matrix 58:107 The Bacillus subtilis extracellular biofilm matrix includes an exopolysaccharide that is critical for the architecture and function of the community. 36865097 12 77 from biosynthesis 1869:1880 arg1 characterization 1818:1833 the sequential characterization 1803:1833 the sequential characterization of the steps in exopolysaccharide biosynthesis 1803:1880 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 3 78 theme comparative 459:469 arg1 analyses 480:487 comparative sequence analyses 459:487 comparative sequence analyses 459:487 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 5 79 theme UDP-di- 877:883 arg1 bacillosamine 895:907 UDP-di- N -acetyl bacillosamine 877:907 UDP-di- N -acetyl bacillosamine 877:907 EpsL catalyzes the first phosphoglycosyl transferase step using UDP-di- N -acetyl bacillosamine as phospho-sugar donor. 36865097 1 80 theme extracellular 80:92 arg1 matrix 102:107 The Bacillus subtilis extracellular biofilm matrix 58:107 The Bacillus subtilis extracellular biofilm matrix 58:107 The Bacillus subtilis extracellular biofilm matrix includes an exopolysaccharide that is critical for the architecture and function of the community. 36865097 1 81 dep architecture 164:175 arg1 the 160:162 the 160:162 the 160:162 The Bacillus subtilis extracellular biofilm matrix includes an exopolysaccharide that is critical for the architecture and function of the community. 36865097 5 82 theme -acetyl 887:893 arg1 bacillosamine 895:907 UDP-di- N -acetyl bacillosamine 877:907 UDP-di- N -acetyl bacillosamine 877:907 EpsL catalyzes the first phosphoglycosyl transferase step using UDP-di- N -acetyl bacillosamine as phospho-sugar donor. 36865097 12 83 theme substrates 1982:1991 arg1 synthesis 1926:1934 chemoenzymatic synthesis 1911:1934 chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates 1911:1991 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 3 84 theme synergistic 388:398 arg1 studies 424:430 synergistic biochemical and genetic studies 388:430 synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway 388:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 7 85 theme reducing 1193:1200 arg1 end 1202:1204 the reducing end 1189:1204 the reducing end of the growing exopolysaccharide unit 1189:1242 Thus, the study defines the first two monosaccharides at the reducing end of the growing exopolysaccharide unit. 36865097 12 86 from characterization 1818:1833 arg1 biosynthesis 1869:1880 exopolysaccharide biosynthesis 1851:1880 exopolysaccharide biosynthesis 1851:1880 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 10 87 theme biofilm 1532:1538 arg1 formation 1540:1548 biofilm formation 1532:1548 biofilm formation 1532:1548 Key to our ability to systematically promote or ablate biofilm formation is a detailed understanding of the biofilm matrix macromolecules. 36865097 11 88 theme essential 1647:1655 arg1 steps 1657:1661 the first two essential steps 1633:1661 the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1633:1737 Here we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway. 36865097 3 89 theme analyses 480:487 arg1 foundation 445:454 a foundation 443:454 a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway 443:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 10 90 theme matrix 1593:1598 arg1 macromolecules 1600:1613 the biofilm matrix macromolecules 1581:1613 the biofilm matrix macromolecules 1581:1613 Key to our ability to systematically promote or ablate biofilm formation is a detailed understanding of the biofilm matrix macromolecules. 36865097 11 91 theme first 1637:1641 arg1 steps 1657:1661 the first two essential steps 1633:1661 the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1633:1737 Here we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway. 36865097 9 92 theme life 1430:1433 arg1 way 1423:1425 the communal way 1410:1425 the communal way of life that microbes adopt to increase survival 1410:1474 IMPORTANCE Biofilms are the communal way of life that microbes adopt to increase survival. 36865097 9 92 theme life 1430:1433 arg1 Biofilms 1397:1404 IMPORTANCE Biofilms 1386:1404 IMPORTANCE Biofilms 1386:1404 IMPORTANCE Biofilms are the communal way of life that microbes adopt to increase survival. 36865097 12 93 theme diphosphate-linked 1956:1973 arg1 substrates 1982:1991 the undecaprenol diphosphate-linked glycan substrates 1939:1991 the undecaprenol diphosphate-linked glycan substrates 1939:1991 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 12 94 theme chemoenzymatic 1911:1924 arg1 synthesis 1926:1934 chemoenzymatic synthesis 1911:1934 chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates 1911:1991 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 36865097 10 95 theme detailed 1555:1562 arg1 understanding 1564:1576 a detailed understanding 1553:1576 a detailed understanding of the biofilm matrix macromolecules 1553:1613 Key to our ability to systematically promote or ablate biofilm formation is a detailed understanding of the biofilm matrix macromolecules. 36865097 10 95 theme detailed 1555:1562 arg1 Key 1477:1479 Key 1477:1479 Key 1477:1479 Key to our ability to systematically promote or ablate biofilm formation is a detailed understanding of the biofilm matrix macromolecules. 36865097 11 96 theme Bacillus 1670:1677 arg1 pathway 1731:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 Here we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway. 36865097 3 97 theme membrane-committed 545:562 arg1 steps 564:568 the first two membrane-committed steps 531:568 the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway 531:614 This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the exopolysaccharide biosynthetic pathway. 36865097 4 98 theme nucleotide 660:669 arg1 donor 677:681 the nucleotide sugar donor 656:681 the nucleotide sugar donor 656:681 By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm exopolysaccharide biosynthetic pathway. 36865097 10 99 theme macromolecules 1600:1613 arg1 understanding 1564:1576 a detailed understanding 1553:1576 a detailed understanding of the biofilm matrix macromolecules 1553:1613 Key to our ability to systematically promote or ablate biofilm formation is a detailed understanding of the biofilm matrix macromolecules. 36865097 10 99 theme macromolecules 1600:1613 arg1 Key 1477:1479 Key 1477:1479 Key 1477:1479 Key to our ability to systematically promote or ablate biofilm formation is a detailed understanding of the biofilm matrix macromolecules. 36865097 11 100 theme exopolysaccharide 1703:1719 arg1 pathway 1731:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway 1666:1737 Here we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide synthesis pathway. 36865097 0 101 theme Early 9:13 arg1 Steps 15:19 Early Steps 9:19 Early Steps in B. subtilis Biofilm Biosynthesis 9:55 Defining Early Steps in B. subtilis Biofilm Biosynthesis. 36865097 12 102 link diphosphate-linked 1956:1973 arg1 substrates 1982:1991 the undecaprenol diphosphate-linked glycan substrates 1939:1991 the undecaprenol diphosphate-linked glycan substrates 1939:1991 Together our studies and approaches provide the foundation for the sequential characterization of the steps in exopolysaccharide biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenol diphosphate-linked glycan substrates. 35682750 0 0 theme Infant 98:103 arg1 Mice 105:108 Infant Mice 98:108 Infant Mice 98:108 Baicalin Alleviates Short-Term Lincomycin-Induced Intestinal and Liver Injury and Inflammation in Infant Mice. 35682750 10 1 theme bacteria 1566:1573 arg1 abundance 1575:1583 anti-inflammatory bacteria abundance 1548:1583 anti-inflammatory bacteria abundance 1548:1583 In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. 35682750 1 2 from gastrointestinal 185:200 arg1 children 238:245 young children 232:245 young children 232:245 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 1 3 theme exposure 169:176 arg1 megadose 145:152 short-term megadose 134:152 short-term megadose of antibiotics exposure 134:176 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 11 4 theme antibiotic-induced 1759:1776 arg1 injury 1778:1783 antibiotic-induced injury 1759:1783 antibiotic-induced injury 1759:1783 Thus, baicalin can ameliorate antibiotic-induced injury and its associated complications such as liver disease. 35682750 10 5 theme anti-inflammatory 1548:1564 arg1 abundance 1575:1583 anti-inflammatory bacteria abundance 1548:1583 anti-inflammatory bacteria abundance 1548:1583 In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. 35682750 7 6 theme intestinal 1034:1043 arg1 cytokines 1058:1066 intestinal inflammatory cytokines 1034:1066 intestinal inflammatory cytokines 1034:1066 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 7 7 theme biosynthesis 1181:1192 arg1 pathways 1194:1201 mucin type O-glycan biosynthesis pathways 1161:1201 mucin type O-glycan biosynthesis pathways 1161:1201 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 7 8 theme inflammatory 1045:1056 arg1 cytokines 1058:1066 intestinal inflammatory cytokines 1034:1066 intestinal inflammatory cytokines 1034:1066 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 8 9 theme liver 1235:1239 arg1 function 1241:1248 liver function 1235:1248 liver function 1235:1248 In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. 35682750 10 10 theme pathogenic 1625:1634 arg1 bacteria 1636:1643 pathogenic bacteria 1625:1643 pathogenic bacteria abundance 1625:1653 In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. 35682750 7 11 theme O-glycan 1172:1179 arg1 pathways 1194:1201 mucin type O-glycan biosynthesis pathways 1161:1201 mucin type O-glycan biosynthesis pathways 1161:1201 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 5 12 theme lincomycin 627:636 arg1 exposure 638:645 lincomycin exposure 627:645 lincomycin exposure 627:645 Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. 35682750 0 13 from Injury 71:76 arg1 Mice 105:108 Infant Mice 98:108 Infant Mice 98:108 Baicalin Alleviates Short-Term Lincomycin-Induced Intestinal and Liver Injury and Inflammation in Infant Mice. 35682750 5 14 theme gut 697:699 arg1 microbiota 701:710 gut microbiota 697:710 gut microbiota 697:710 Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. 35682750 10 15 dep reduced 1617:1623 arg1 Proteobacteria 1656:1669 Proteobacteria 1656:1669 Proteobacteria 1656:1669 In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. 35682750 4 16 theme harm 503:506 arg1 measures 519:526 the harm and rescue measures 499:526 the harm and rescue measures of antibiotics from the perspective of the gut-liver system 499:586 Studies on the harm and rescue measures of antibiotics from the perspective of the gut-liver system are lacking. 35682750 4 17 from measures 519:526 arg1 perspective 552:562 the perspective 548:562 the perspective of the gut-liver system 548:586 Studies on the harm and rescue measures of antibiotics from the perspective of the gut-liver system are lacking. 35682750 8 18 theme lipid 1326:1330 arg1 degradation 1332:1342 lipid degradation 1326:1342 lipid degradation 1326:1342 In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. 35682750 7 19 theme mucin 1161:1165 arg1 pathways 1194:1201 mucin type O-glycan biosynthesis pathways 1161:1201 mucin type O-glycan biosynthesis pathways 1161:1201 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 4 20 from perspective 552:562 arg1 antibiotics 531:541 antibiotics 531:541 antibiotics from the perspective of the gut-liver system 531:586 Studies on the harm and rescue measures of antibiotics from the perspective of the gut-liver system are lacking. 35682750 4 20 from perspective 552:562 arg1 measures 519:526 the harm and rescue measures 499:526 the harm and rescue measures of antibiotics from the perspective of the gut-liver system 499:586 Studies on the harm and rescue measures of antibiotics from the perspective of the gut-liver system are lacking. 35682750 11 21 theme associated 1793:1802 arg1 complications 1804:1816 its associated complications 1789:1816 its associated complications such as liver disease 1789:1838 Thus, baicalin can ameliorate antibiotic-induced injury and its associated complications such as liver disease. 35682750 11 21 theme associated 1793:1802 arg1 disease 1832:1838 liver disease 1826:1838 liver disease 1826:1838 Thus, baicalin can ameliorate antibiotic-induced injury and its associated complications such as liver disease. 35682750 7 22 theme type 1167:1170 arg1 pathways 1194:1201 mucin type O-glycan biosynthesis pathways 1161:1201 mucin type O-glycan biosynthesis pathways 1161:1201 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 2 23 theme liver 301:305 arg1 pathogenesis 375:386 a poorly understood pathogenesis 355:386 a poorly understood pathogenesis 355:386 Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. 35682750 2 23 theme liver 301:305 arg1 reactions 307:315 Antibiotic-induced intestinal and liver reactions 267:315 Antibiotic-induced intestinal and liver reactions 267:315 Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. 35682750 3 24 theme antibiotics 475:485 arg1 effects 464:470 the adverse effects 452:470 the adverse effects of antibiotics 452:485 It is, therefore, necessary to develop strategies for reducing the adverse effects of antibiotics. 35682750 8 25 theme lipid 1382:1386 arg1 synthesis 1388:1396 lipid synthesis 1382:1396 lipid synthesis in lincomycin-treated mice 1382:1423 In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. 35682750 4 26 theme rescue 512:517 arg1 measures 519:526 the harm and rescue measures 499:526 the harm and rescue measures of antibiotics from the perspective of the gut-liver system 499:586 Studies on the harm and rescue measures of antibiotics from the perspective of the gut-liver system are lacking. 35682750 7 27 theme decreased 1014:1022 arg1 levels 1024:1029 the decreased levels 1010:1029 the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation 1010:1144 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 7 28 theme Transcriptome 923:935 arg1 analysis 937:944 Transcriptome analysis 923:944 Transcriptome analysis 923:944 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 3 29 theme adverse 456:462 arg1 effects 464:470 the adverse effects 452:470 the adverse effects of antibiotics 452:485 It is, therefore, necessary to develop strategies for reducing the adverse effects of antibiotics. 35682750 5 30 theme immune-mediated 749:763 arg1 injury 765:770 immune-mediated injury 749:770 immune-mediated injury 749:770 Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. 35682750 1 31 from effects 123:129 arg1 liver 206:210 liver 206:210 liver 206:210 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 1 31 from effects 123:129 arg1 gastrointestinal 185:200 gastrointestinal 185:200 gastrointestinal 185:200 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 5 32 theme body 655:658 arg1 weight 660:665 body weight 655:665 body weight 655:665 Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. 35682750 8 33 theme genes 1284:1288 arg1 expression 1270:1279 the expression 1266:1279 the expression of genes involved in bile acid secretion and lipid degradation 1266:1342 In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. 35682750 10 34 dep Proteobacteria 1656:1669 arg1 Klebsiella 1672:1681 Klebsiella 1672:1681 Klebsiella 1672:1681 In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. 35682750 10 34 dep Proteobacteria 1656:1669 arg1 Citrobacter 1688:1698 Citrobacter 1688:1698 Citrobacter 1688:1698 In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. 35682750 4 35 theme system 581:586 arg1 perspective 552:562 the perspective 548:562 the perspective of the gut-liver system 548:586 Studies on the harm and rescue measures of antibiotics from the perspective of the gut-liver system are lacking. 35682750 8 36 from synthesis 1388:1396 arg1 mice 1420:1423 lincomycin-treated mice 1401:1423 lincomycin-treated mice 1401:1423 In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. 35682750 8 37 theme lincomycin-treated 1401:1418 arg1 mice 1420:1423 lincomycin-treated mice 1401:1423 lincomycin-treated mice 1401:1423 In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. 35682750 1 38 theme tissue 212:217 arg1 reactions 219:227 tissue reactions 212:227 tissue reactions 212:227 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 10 39 theme lincomycin-treated 1704:1721 arg1 mice 1723:1726 lincomycin-treated mice 1704:1726 lincomycin-treated mice 1704:1726 In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. 35682750 7 40 theme Th17 1120:1123 arg1 differentiation 1130:1144 Th17 cell differentiation 1120:1144 Th17 cell differentiation 1120:1144 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 1 41 theme adverse 115:121 arg1 effects 123:129 The adverse effects 111:129 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children 111:245 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 10 42 dep improved 1539:1546 arg1 Coprobacillus 1598:1610 Coprobacillus 1598:1610 Coprobacillus 1598:1610 In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. 35682750 10 42 dep improved 1539:1546 arg1 Blautia 1586:1592 Blautia 1586:1592 Blautia 1586:1592 In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. 35682750 4 43 from Studies 488:494 arg1 measures 519:526 the harm and rescue measures 499:526 the harm and rescue measures of antibiotics from the perspective of the gut-liver system 499:586 Studies on the harm and rescue measures of antibiotics from the perspective of the gut-liver system are lacking. 35682750 11 44 theme liver 1826:1830 arg1 disease 1832:1838 liver disease 1826:1838 liver disease 1826:1838 Thus, baicalin can ameliorate antibiotic-induced injury and its associated complications such as liver disease. 35682750 5 45 theme lipid 829:833 arg1 metabolism 835:844 lipid metabolism 829:844 lipid metabolism 829:844 Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. 35682750 7 46 theme cell 1125:1128 arg1 differentiation 1130:1144 Th17 cell differentiation 1120:1144 Th17 cell differentiation 1120:1144 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 0 47 from Inflammation 82:93 arg1 Mice 105:108 Infant Mice 98:108 Infant Mice 98:108 Baicalin Alleviates Short-Term Lincomycin-Induced Intestinal and Liver Injury and Inflammation in Infant Mice. 35682750 1 48 theme young 232:236 arg1 children 238:245 young children 232:245 young children 232:245 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 8 49 theme bile 1302:1305 arg1 secretion 1312:1320 bile acid secretion 1302:1320 bile acid secretion 1302:1320 In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. 35682750 9 50 theme intestinal 1450:1459 arg1 immunity 1461:1468 intestinal immunity 1450:1468 intestinal immunity 1450:1468 Bile acids can regulate intestinal immunity and strengthen hepatoenteric circulation. 35682750 5 51 theme microbiota 701:710 arg1 composition 682:692 the composition 678:692 the composition of gut microbiota and intestinal morphology 678:736 Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. 35682750 9 52 theme Bile 1426:1429 arg1 acids 1431:1435 Bile acids 1426:1435 Bile acids 1426:1435 Bile acids can regulate intestinal immunity and strengthen hepatoenteric circulation. 35682750 5 53 theme intestinal 716:725 arg1 morphology 727:736 intestinal morphology 716:736 intestinal morphology 716:736 Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. 35682750 0 54 theme Liver 65:69 arg1 Injury 71:76 Liver Injury 65:76 Liver Injury 65:76 Baicalin Alleviates Short-Term Lincomycin-Induced Intestinal and Liver Injury and Inflammation in Infant Mice. 35682750 4 55 theme gut-liver 571:579 arg1 system 581:586 the gut-liver system 567:586 the gut-liver system 567:586 Studies on the harm and rescue measures of antibiotics from the perspective of the gut-liver system are lacking. 35682750 9 56 theme hepatoenteric 1485:1497 arg1 circulation 1499:1509 hepatoenteric circulation 1485:1509 hepatoenteric circulation 1485:1509 Bile acids can regulate intestinal immunity and strengthen hepatoenteric circulation. 35682750 1 57 dep gastrointestinal 185:200 arg1 reactions 219:227 tissue reactions 212:227 tissue reactions 212:227 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 1 57 dep gastrointestinal 185:200 arg1 the 181:183 the 181:183 the 181:183 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 7 58 theme genes 1086:1090 arg1 expression 1072:1081 expression 1072:1081 expression of genes that regulate Th1, Th2, and Th17 cell differentiation 1072:1144 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 7 58 theme genes 1086:1090 arg1 cytokines 1058:1066 intestinal inflammatory cytokines 1034:1066 intestinal inflammatory cytokines 1034:1066 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 2 59 dep unpredictable 329:341 arg1 pathogenesis 375:386 a poorly understood pathogenesis 355:386 a poorly understood pathogenesis 355:386 Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. 35682750 2 59 dep unpredictable 329:341 arg1 reactions 307:315 Antibiotic-induced intestinal and liver reactions 267:315 Antibiotic-induced intestinal and liver reactions 267:315 Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. 35682750 1 60 from children 238:245 arg1 gastrointestinal 185:200 gastrointestinal 185:200 gastrointestinal 185:200 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 6 61 theme lincomycin-induced 895:912 arg1 changes 914:920 the lincomycin-induced changes 891:920 the lincomycin-induced changes 891:920 However, baicalin administration attenuated the lincomycin-induced changes. 35682750 6 62 theme baicalin 856:863 arg1 administration 865:878 baicalin administration 856:878 baicalin administration 856:878 However, baicalin administration attenuated the lincomycin-induced changes. 35682750 1 63 theme short-term 134:143 arg1 megadose 145:152 short-term megadose 134:152 short-term megadose of antibiotics exposure 134:176 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 5 64 theme morphology 727:736 arg1 composition 682:692 the composition 678:692 the composition of gut microbiota and intestinal morphology 678:736 Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. 35682750 2 65 theme intestinal 286:295 arg1 pathogenesis 375:386 a poorly understood pathogenesis 355:386 a poorly understood pathogenesis 355:386 Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. 35682750 2 65 theme intestinal 286:295 arg1 reactions 307:315 Antibiotic-induced intestinal and liver reactions 267:315 Antibiotic-induced intestinal and liver reactions 267:315 Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. 35682750 7 66 theme expression 1072:1081 arg1 levels 1024:1029 the decreased levels 1010:1029 the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation 1010:1144 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 1 67 theme megadose 145:152 arg1 effects 123:129 The adverse effects 111:129 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children 111:245 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 35682750 2 68 theme understood 364:373 arg1 pathogenesis 375:386 a poorly understood pathogenesis 355:386 a poorly understood pathogenesis 355:386 Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. 35682750 2 68 theme understood 364:373 arg1 reactions 307:315 Antibiotic-induced intestinal and liver reactions 267:315 Antibiotic-induced intestinal and liver reactions 267:315 Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. 35682750 5 69 theme liver 797:801 arg1 dysfunction 803:813 liver dysfunction 797:813 liver dysfunction 797:813 Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. 35682750 2 70 theme Antibiotic-induced 267:284 arg1 pathogenesis 375:386 a poorly understood pathogenesis 355:386 a poorly understood pathogenesis 355:386 Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. 35682750 2 70 theme Antibiotic-induced 267:284 arg1 reactions 307:315 Antibiotic-induced intestinal and liver reactions 267:315 Antibiotic-induced intestinal and liver reactions 267:315 Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. 35682750 10 71 theme bacteria 1636:1643 arg1 abundance 1645:1653 pathogenic bacteria abundance 1625:1653 pathogenic bacteria abundance 1625:1653 In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. 35682750 8 72 theme acid 1307:1310 arg1 secretion 1312:1320 bile acid secretion 1302:1320 bile acid secretion 1302:1320 In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. 35682750 4 73 theme antibiotics 531:541 arg1 measures 519:526 the harm and rescue measures 499:526 the harm and rescue measures of antibiotics from the perspective of the gut-liver system 499:586 Studies on the harm and rescue measures of antibiotics from the perspective of the gut-liver system are lacking. 35682750 7 74 theme cytokines 1058:1066 arg1 levels 1024:1029 the decreased levels 1010:1029 the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation 1010:1144 Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. 35682750 1 75 theme antibiotics 157:167 arg1 exposure 169:176 antibiotics exposure 157:176 antibiotics exposure 157:176 The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. 36050658 3 0 theme CC 512:513 arg1 patients 515:522 41 CC patients 509:522 41 CC patients 509:522 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 3 1 theme shotgun 554:560 arg1 sequencing 562:571 whole-genome shotgun sequencing 541:571 whole-genome shotgun sequencing 541:571 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 1 2 theme increased 271:279 arg1 diversity 285:293 increased gut diversity 271:293 increased gut diversity 271:293 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 36050658 7 3 with patients 1238:1245 arg1 tumors 1275:1280 larger, advanced stage tumors 1252:1280 larger, advanced stage tumors 1252:1280 This community was prevalent in patients with larger, advanced stage tumors. 36050658 4 4 theme Significant 693:703 arg1 association 705:715 RESULTS Significant association 685:715 RESULTS Significant association of molecular functions encoded by the metagenomes 685:765 RESULTS Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. 36050658 3 5 theme taxonomic 581:589 arg1 structures 591:600 taxonomic structures 581:600 taxonomic structures 581:600 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 5 6 theme distributions 869:881 arg1 Profiling 812:820 Profiling 812:820 Profiling of the molecular function abundances and their distributions 812:881 Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. 36050658 8 7 theme fast 1354:1357 arg1 growth 1359:1364 fast growth 1354:1364 fast growth 1354:1364 Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. 36050658 0 8 theme taxonomic 130:138 arg1 structure 140:148 distinct taxonomic structure 121:148 distinct taxonomic structure 121:148 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 5 9 theme abundances 848:857 arg1 Profiling 812:820 Profiling 812:820 Profiling of the molecular function abundances and their distributions 812:881 Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. 36050658 1 10 theme CC 232:233 arg1 patients 236:243 cervical cancer (CC) patients 215:243 cervical cancer (CC) patients 215:243 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 36050658 6 11 theme Community 1006:1014 arg1 A 1016:1016 Community A 1006:1016 Community A (Clostridia and Proteobacteria predominant) 1006:1060 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 8 12 theme oxidative 1374:1382 arg1 phosphorylation 1384:1398 active oxidative phosphorylation 1367:1398 active oxidative phosphorylation 1367:1398 Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. 36050658 5 13 theme taxonomic 984:992 arg1 structures 994:1003 taxonomic structures 984:1003 taxonomic structures 984:1003 Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. 36050658 0 14 theme stage 48:52 arg1 cancers 63:69 larger, advanced stage cervical cancers 31:69 larger, advanced stage cervical cancers 31:69 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 1 15 theme BACKGROUND 151:160 arg1 composition 187:197 BACKGROUND Gut microbiome community composition 151:197 BACKGROUND Gut microbiome community composition 151:197 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 36050658 4 16 theme functions 730:738 arg1 association 705:715 RESULTS Significant association 685:715 RESULTS Significant association of molecular functions encoded by the metagenomes 685:765 RESULTS Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. 36050658 1 17 theme microbiome 166:175 arg1 composition 187:197 BACKGROUND Gut microbiome community composition 151:197 BACKGROUND Gut microbiome community composition 151:197 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 36050658 0 18 from Metagenomes 0:10 arg1 cancers 63:69 larger, advanced stage cervical cancers 31:69 larger, advanced stage cervical cancers 31:69 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 7 19 dep larger 1252:1257 arg1 advanced 1260:1267 advanced 1260:1267 advanced 1260:1267 This community was prevalent in patients with larger, advanced stage tumors. 36050658 8 20 theme vitamins 1419:1426 arg1 growth 1359:1364 fast growth 1354:1364 fast growth 1354:1364 Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. 36050658 8 20 theme vitamins 1419:1426 arg1 phosphorylation 1384:1398 active oxidative phosphorylation 1367:1398 active oxidative phosphorylation 1367:1398 Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. 36050658 8 20 theme vitamins 1419:1426 arg1 production 1405:1414 production 1405:1414 production of vitamins 1405:1426 Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. 36050658 0 21 theme enhanced 76:83 arg1 functionalities 101:115 enhanced mucus degrading functionalities 76:115 enhanced mucus degrading functionalities 76:115 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 6 22 theme predominant 1049:1059 arg1 Proteobacteria 1034:1047 Proteobacteria predominant 1034:1059 Proteobacteria predominant 1034:1059 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 10 23 theme degrading 1551:1559 arg1 communities 1571:1581 mucus degrading microbial communities 1545:1581 mucus degrading microbial communities 1545:1581 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 0 24 theme degrading 91:99 arg1 functionalities 101:115 enhanced mucus degrading functionalities 76:115 enhanced mucus degrading functionalities 76:115 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 6 25 theme mucus 1138:1142 arg1 degradation 1151:1161 mucus glycan degradation 1138:1161 mucus glycan degradation 1138:1161 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 10 26 from enrichment 1531:1540 arg1 metagenomes 1593:1603 rectal metagenomes 1586:1603 rectal metagenomes of CC patients 1586:1618 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 2 27 theme species 398:404 arg1 functions 366:374 functions 366:374 functions of specific microbial species adjoining the mucus layer 366:430 We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC. 36050658 5 28 theme function 839:846 arg1 abundances 848:857 the molecular function abundances 825:857 the molecular function abundances 825:857 Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. 36050658 1 29 theme gut 281:283 arg1 diversity 285:293 increased gut diversity 271:293 increased gut diversity 271:293 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 36050658 10 30 theme rectal 1586:1591 arg1 metagenomes 1593:1603 rectal metagenomes 1586:1603 rectal metagenomes of CC patients 1586:1618 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 4 31 theme initial 782:788 arg1 size 796:799 initial tumor size 782:799 initial tumor size 782:799 RESULTS Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. 36050658 3 32 theme METHOD 471:476 arg1 Metagenomes 478:488 METHOD Metagenomes 471:488 METHOD Metagenomes of rectal swabs in 41 CC patients 471:522 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 0 33 theme rectal 15:20 arg1 swabs 22:26 rectal swabs 15:26 rectal swabs 15:26 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 10 34 theme communities 1571:1581 arg1 enrichment 1531:1540 enrichment 1531:1540 enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients 1531:1618 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 3 35 theme clinical 659:666 arg1 characteristics 668:682 patient's clinical characteristics 649:682 patient's clinical characteristics 649:682 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 5 36 theme microbial 896:904 arg1 communities 906:916 2 microbial communities 894:916 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures 894:1003 Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. 36050658 6 37 theme pathways 1100:1107 arg1 activity 1088:1095 high activity 1083:1095 high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts 1083:1203 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 10 38 theme patients 1611:1618 arg1 metagenomes 1593:1603 rectal metagenomes 1586:1603 rectal metagenomes of CC patients 1586:1618 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 3 39 theme swabs 500:504 arg1 Metagenomes 478:488 METHOD Metagenomes 471:488 METHOD Metagenomes of rectal swabs in 41 CC patients 471:522 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 3 40 from Metagenomes 478:488 arg1 patients 515:522 41 CC patients 509:522 41 CC patients 509:522 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 6 41 theme degradation 1182:1192 arg1 byproducts 1194:1203 degradation byproducts 1182:1203 degradation byproducts 1182:1203 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 10 42 theme larger 1640:1645 arg1 tumors 1668:1673 larger, more advanced stage tumors 1640:1673 larger, more advanced stage tumors 1640:1673 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 2 43 theme mucus 420:424 arg1 layer 426:430 the mucus layer 416:430 the mucus layer 416:430 We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC. 36050658 0 44 contain have 71:74 arg2 functionalities 101:115 enhanced mucus degrading functionalities 76:115 enhanced mucus degrading functionalities 76:115 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 0 44 contain have 71:74 arg1 Metagenomes 0:10 Metagenomes 0:10 Metagenomes of rectal swabs in larger, advanced stage cervical cancers 0:69 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 0 44 contain have 71:74 arg2 structure 140:148 distinct taxonomic structure 121:148 distinct taxonomic structure 121:148 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 2 45 theme specific 379:386 arg1 species 398:404 specific microbial species 379:404 specific microbial species adjoining the mucus layer 379:430 We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC. 36050658 9 46 theme smaller 1475:1481 arg1 tumors 1496:1501 smaller, early-stage tumors 1475:1501 smaller, early-stage tumors 1475:1501 This community was prevalent in patients with smaller, early-stage tumors. 36050658 10 47 theme stage 1662:1666 arg1 tumors 1668:1673 larger, more advanced stage tumors 1640:1673 larger, more advanced stage tumors 1640:1673 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 3 48 theme whole-genome 541:552 arg1 sequencing 562:571 whole-genome shotgun sequencing 541:571 whole-genome shotgun sequencing 541:571 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 1 49 theme community 177:185 arg1 composition 187:197 BACKGROUND Gut microbiome community composition 151:197 BACKGROUND Gut microbiome community composition 151:197 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 36050658 8 50 theme predominant 1320:1330 arg1 Bacteroidia 1308:1318 Bacteroidia predominant 1308:1330 Bacteroidia predominant 1308:1330 Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. 36050658 8 50 theme predominant 1320:1330 arg1 B 1305:1305 community B 1295:1305 community B (Bacteroidia predominant) 1295:1331 Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. 36050658 0 51 theme distinct 121:128 arg1 structure 140:148 distinct taxonomic structure 121:148 distinct taxonomic structure 121:148 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 1 52 theme cervical 215:222 arg1 patients 236:243 cervical cancer (CC) patients 215:243 cervical cancer (CC) patients 215:243 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 36050658 9 53 dep smaller 1475:1481 arg1 early-stage 1484:1494 early-stage 1484:1494 early-stage 1484:1494 This community was prevalent in patients with smaller, early-stage tumors. 36050658 3 54 theme molecular 603:611 arg1 functions 613:621 molecular functions 603:621 molecular functions 603:621 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 4 55 theme RESULTS 685:691 arg1 association 705:715 RESULTS Significant association 685:715 RESULTS Significant association of molecular functions encoded by the metagenomes 685:765 RESULTS Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. 36050658 6 56 dep A 1016:1016 arg1 Clostridia 1019:1028 Clostridia 1019:1028 Clostridia 1019:1028 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 6 56 dep A 1016:1016 arg1 Proteobacteria 1034:1047 Proteobacteria predominant 1034:1059 Proteobacteria predominant 1034:1059 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 5 57 theme distinct 960:967 arg1 metabolism 969:978 distinct metabolism 960:978 distinct metabolism 960:978 Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. 36050658 8 58 theme community 1295:1303 arg1 Bacteroidia 1308:1318 Bacteroidia predominant 1308:1330 Bacteroidia predominant 1308:1330 Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. 36050658 8 58 theme community 1295:1303 arg1 B 1305:1305 community B 1295:1305 community B (Bacteroidia predominant) 1295:1331 Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. 36050658 10 59 dep larger 1640:1645 arg1 advanced 1653:1660 advanced 1653:1660 advanced 1653:1660 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 3 60 theme metabolic 628:636 arg1 pathway 638:644 metabolic pathway 628:644 metabolic pathway 628:644 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 8 61 theme active 1367:1372 arg1 phosphorylation 1384:1398 active oxidative phosphorylation 1367:1398 active oxidative phosphorylation 1367:1398 Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. 36050658 0 62 theme cervical 54:61 arg1 cancers 63:69 larger, advanced stage cervical cancers 31:69 larger, advanced stage cervical cancers 31:69 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 6 63 theme high 1083:1086 arg1 activity 1088:1095 high activity 1083:1095 high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts 1083:1203 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 9 64 from prevalent 1448:1456 arg1 patients 1461:1468 patients 1461:1468 patients with smaller, early-stage tumors 1461:1501 This community was prevalent in patients with smaller, early-stage tumors. 36050658 1 65 theme Gut 162:164 arg1 composition 187:197 BACKGROUND Gut microbiome community composition 151:197 BACKGROUND Gut microbiome community composition 151:197 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 36050658 7 66 from prevalent 1225:1233 arg1 patients 1238:1245 patients 1238:1245 patients with larger, advanced stage tumors 1238:1280 This community was prevalent in patients with larger, advanced stage tumors. 36050658 4 67 theme molecular 720:728 arg1 functions 730:738 molecular functions 720:738 molecular functions encoded by the metagenomes 720:765 RESULTS Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. 36050658 0 68 theme mucus 85:89 arg1 functionalities 101:115 enhanced mucus degrading functionalities 76:115 enhanced mucus degrading functionalities 76:115 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 7 69 from patients 1238:1245 arg1 prevalent 1225:1233 prevalent 1225:1233 prevalent 1225:1233 This community was prevalent in patients with larger, advanced stage tumors. 36050658 4 70 theme tumor 790:794 arg1 size 796:799 initial tumor size 782:799 initial tumor size 782:799 RESULTS Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. 36050658 1 71 theme cancer 224:229 arg1 patients 236:243 cervical cancer (CC) patients 215:243 cervical cancer (CC) patients 215:243 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 36050658 6 72 theme glycan 1144:1149 arg1 degradation 1151:1161 mucus glycan degradation 1138:1161 mucus glycan degradation 1138:1161 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 10 73 theme mucus 1545:1549 arg1 communities 1571:1581 mucus degrading microbial communities 1545:1581 mucus degrading microbial communities 1545:1581 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 5 74 theme molecular 829:837 arg1 abundances 848:857 the molecular function abundances 825:857 the molecular function abundances 825:857 Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. 36050658 2 75 theme microbial 388:396 arg1 species 398:404 specific microbial species 379:404 specific microbial species adjoining the mucus layer 379:430 We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC. 36050658 0 76 theme swabs 22:26 arg1 Metagenomes 0:10 Metagenomes 0:10 Metagenomes of rectal swabs in larger, advanced stage cervical cancers 0:69 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 6 77 theme stress 1121:1126 arg1 response 1128:1135 stress response 1121:1135 stress response 1121:1135 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 0 78 theme larger 31:36 arg1 cancers 63:69 larger, advanced stage cervical cancers 31:69 larger, advanced stage cervical cancers 31:69 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 10 79 theme microbial 1561:1569 arg1 communities 1571:1581 mucus degrading microbial communities 1545:1581 mucus degrading microbial communities 1545:1581 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 7 80 theme stage 1269:1273 arg1 tumors 1275:1280 larger, advanced stage tumors 1252:1280 larger, advanced stage tumors 1252:1280 This community was prevalent in patients with larger, advanced stage tumors. 36050658 1 81 theme improved 314:321 arg1 outcomes 323:330 improved outcomes 314:330 improved outcomes after treatment 314:346 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 36050658 0 82 dep larger 31:36 arg1 advanced 39:46 advanced 39:46 advanced 39:46 Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure. 36050658 2 83 theme CC 467:468 arg1 biology 456:462 the biology 452:462 the biology of CC 452:468 We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC. 36050658 10 84 theme CC 1608:1609 arg1 patients 1611:1618 CC patients 1608:1618 CC patients 1608:1618 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 5 85 dep communities 906:916 arg1 having 953:958 having 953:958 having distinct metabolism and taxonomic structures 953:1003 Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. 36050658 5 85 dep communities 906:916 arg1 co-existing 918:928 co-existing 918:928 co-existing in each metagenome 918:947 Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. 36050658 9 86 from patients 1461:1468 arg1 prevalent 1448:1456 prevalent 1448:1456 prevalent 1448:1456 This community was prevalent in patients with smaller, early-stage tumors. 36050658 6 87 theme byproducts 1194:1203 arg1 utilization 1167:1177 utilization 1167:1177 utilization of degradation byproducts 1167:1203 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 6 87 theme byproducts 1194:1203 arg1 degradation 1151:1161 mucus glycan degradation 1138:1161 mucus glycan degradation 1138:1161 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 6 87 theme byproducts 1194:1203 arg1 response 1128:1135 stress response 1121:1135 stress response 1121:1135 Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. 36050658 3 88 theme rectal 493:498 arg1 swabs 500:504 rectal swabs 493:504 rectal swabs 493:504 METHOD Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. 36050658 10 89 dep CONCLUSIONS 1504:1514 arg1 associated 1624:1633 associated 1624:1633 was associated with larger, more advanced stage tumors 1620:1673 CONCLUSIONS In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors. 36050658 9 90 with patients 1461:1468 arg1 tumors 1496:1501 smaller, early-stage tumors 1475:1501 smaller, early-stage tumors 1475:1501 This community was prevalent in patients with smaller, early-stage tumors. 36050658 7 91 theme larger 1252:1257 arg1 tumors 1275:1280 larger, advanced stage tumors 1252:1280 larger, advanced stage tumors 1252:1280 This community was prevalent in patients with larger, advanced stage tumors. 36050658 1 92 theme healthy 249:255 arg1 controls 257:264 healthy controls 249:264 healthy controls 249:264 BACKGROUND Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. 37385076 4 0 theme elapid 854:859 arg1 NK-LAAO 887:893 NK-LAAO 887:893 NK-LAAO 887:893 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 4 0 theme elapid 854:859 arg1 LAAO 881:884 the Thailand elapid snake Naja kaouthia LAAO 841:884 the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO) 841:894 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 2 1 theme overall 343:349 arg1 responses 351:359 the overall responses 339:359 the overall responses of cancer cells to these redox enzymes 339:398 However, multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes remain ambiguous. 37385076 4 2 theme Naja 867:870 arg1 NK-LAAO 887:893 NK-LAAO 887:893 NK-LAAO 887:893 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 4 2 theme Naja 867:870 arg1 LAAO 881:884 the Thailand elapid snake Naja kaouthia LAAO 841:884 the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO) 841:894 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 6 3 theme redox 1254:1258 arg1 reactions 1260:1268 the enzymatic redox reactions 1240:1268 the enzymatic redox reactions 1240:1268 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 3 4 theme site-related 492:503 arg1 residues 505:512 active site-related residues 485:512 active site-related residues 485:512 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 1 5 theme anticancer 255:264 arg1 therapeutics 266:277 anticancer therapeutics 255:277 anticancer therapeutics 255:277 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 6 6 with cytotoxicity 1074:1085 arg1 magnitude 1096:1104 the magnitude 1092:1104 the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions 1092:1268 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 7 7 theme cancer 1395:1400 arg1 cells 1402:1406 cancer cells 1395:1406 cancer cells 1395:1406 Unexpectedly, we discover a tolerant mechanism deployed by cancer cells to dampen the anticancer activities of NK-LAAO. 37385076 1 8 theme venom 168:172 arg1 candidates 240:249 promising candidates 230:249 promising candidates for anticancer therapeutics 230:277 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 1 8 theme venom 168:172 arg1 svLAAOs 197:203 svLAAOs 197:203 svLAAOs 197:203 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 1 8 theme venom 168:172 arg1 oxidases 187:194 Snake venom l-amino acid oxidases 162:194 Snake venom l-amino acid oxidases (svLAAOs) 162:204 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 7 9 theme anticancer 1422:1431 arg1 activities 1433:1442 the anticancer activities 1418:1442 the anticancer activities of NK-LAAO 1418:1453 Unexpectedly, we discover a tolerant mechanism deployed by cancer cells to dampen the anticancer activities of NK-LAAO. 37385076 6 10 theme hydrogen 1150:1157 arg1 H2O2 1169:1172 H2O2 1169:1172 H2O2 1169:1172 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 6 10 theme hydrogen 1150:1157 arg1 peroxide 1159:1166 extracellular hydrogen peroxide 1136:1166 extracellular hydrogen peroxide (H2O2) 1136:1173 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 9 11 theme cancer 1696:1701 arg1 cells 1703:1707 cancer cells 1696:1707 cancer cells 1696:1707 Accordingly, IL-6 silencing renders cancer cells vulnerable to NK-LAAO-induced oxidative stress together with abrogating NK-LAAO-stimulated metastatic acquisition. 37385076 3 12 theme catalytic 577:585 arg1 residue 587:593 the previously proposed critical catalytic residue 544:593 the previously proposed critical catalytic residue His 223 544:601 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 1 13 theme acid 182:185 arg1 candidates 240:249 promising candidates 230:249 promising candidates for anticancer therapeutics 230:277 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 1 13 theme acid 182:185 arg1 svLAAOs 197:203 svLAAOs 197:203 svLAAOs 197:203 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 1 13 theme acid 182:185 arg1 oxidases 187:194 Snake venom l-amino acid oxidases 162:194 Snake venom l-amino acid oxidases (svLAAOs) 162:204 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 7 14 theme tolerant 1364:1371 arg1 mechanism 1373:1381 a tolerant mechanism 1362:1381 a tolerant mechanism deployed by cancer cells to dampen the anticancer activities of NK-LAAO 1362:1453 Unexpectedly, we discover a tolerant mechanism deployed by cancer cells to dampen the anticancer activities of NK-LAAO. 37385076 3 15 theme proposed 559:566 arg1 residue 587:593 the previously proposed critical catalytic residue 544:593 the previously proposed critical catalytic residue His 223 544:601 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 9 16 theme IL-6 1673:1676 arg1 silencing 1678:1686 IL-6 silencing 1673:1686 IL-6 silencing 1673:1686 Accordingly, IL-6 silencing renders cancer cells vulnerable to NK-LAAO-induced oxidative stress together with abrogating NK-LAAO-stimulated metastatic acquisition. 37385076 10 17 theme therapies 2026:2034 arg1 effectiveness 1984:1996 the effectiveness 1980:1996 the effectiveness of svLAAOs-based anticancer therapies 1980:2034 Collectively, our study urges caution when using svLAAOs in cancer treatment and identifies the Panx1/iCa2+/IL-6 axis as a therapeutic target for improving the effectiveness of svLAAOs-based anticancer therapies. 37385076 4 18 theme LAAO 881:884 arg1 potentials 827:836 the structural, biochemical, and anticancer therapeutic potentials 771:836 the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO) 771:894 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 10 19 theme svLAAOs-based 2001:2013 arg1 therapies 2026:2034 svLAAOs-based anticancer therapies 2001:2034 svLAAOs-based anticancer therapies 2001:2034 Collectively, our study urges caution when using svLAAOs in cancer treatment and identifies the Panx1/iCa2+/IL-6 axis as a therapeutic target for improving the effectiveness of svLAAOs-based anticancer therapies. 37385076 0 20 theme 1-mediated 125:134 arg1 expression 150:159 pannexin 1-mediated interleukin-6 expression 116:159 pannexin 1-mediated interleukin-6 expression 116:159 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 6 21 theme oxygen 1202:1207 arg1 ROS 1218:1220 ROS 1218:1220 ROS 1218:1220 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 6 21 theme oxygen 1202:1207 arg1 species 1209:1215 intracellular reactive oxygen species 1179:1215 intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions 1179:1268 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 0 22 theme expression 150:159 arg1 Role 108:111 Role 108:111 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 0:160 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 0 23 from effect 80:85 arg1 treatment 97:105 cancer treatment 90:105 cancer treatment 90:105 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 6 24 theme intracellular 1179:1191 arg1 ROS 1218:1220 ROS 1218:1220 ROS 1218:1220 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 6 24 theme intracellular 1179:1191 arg1 species 1209:1215 intracellular reactive oxygen species 1179:1215 intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions 1179:1268 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 9 25 theme oxidative 1739:1747 arg1 stress 1749:1754 NK-LAAO-induced oxidative stress 1723:1754 NK-LAAO-induced oxidative stress together with abrogating NK-LAAO-stimulated metastatic acquisition 1723:1821 Accordingly, IL-6 silencing renders cancer cells vulnerable to NK-LAAO-induced oxidative stress together with abrogating NK-LAAO-stimulated metastatic acquisition. 37385076 0 26 theme double-edged 61:72 arg1 effect 80:85 its double-edged sword effect 57:85 its double-edged sword effect on cancer treatment 57:105 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 0 27 theme effect 80:85 arg1 mechanism 7:15 Action mechanism 0:15 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 0:160 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 2 28 theme redox 386:390 arg1 enzymes 392:398 these redox enzymes 380:398 these redox enzymes 380:398 However, multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes remain ambiguous. 37385076 0 29 theme cancer 90:95 arg1 treatment 97:105 cancer treatment 90:105 cancer treatment 90:105 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 6 30 theme oxidative 1048:1056 arg1 cytotoxicity 1074:1085 substantial oxidative stress-mediated cytotoxicity 1036:1085 substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions 1036:1268 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 9 31 theme metastatic 1800:1809 arg1 acquisition 1811:1821 NK-LAAO-stimulated metastatic acquisition 1781:1821 NK-LAAO-stimulated metastatic acquisition 1781:1821 Accordingly, IL-6 silencing renders cancer cells vulnerable to NK-LAAO-induced oxidative stress together with abrogating NK-LAAO-stimulated metastatic acquisition. 37385076 0 32 theme Action 0:5 arg1 mechanism 7:15 Action mechanism 0:15 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 0:160 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 8 33 theme NK-LAAO 1456:1462 arg1 treatment 1464:1472 NK-LAAO treatment 1456:1472 NK-LAAO treatment 1456:1472 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37385076 4 34 theme svLAAOs 735:741 arg1 mechanism 711:719 the action mechanism 700:719 the action mechanism of the elapid svLAAOs 700:741 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 3 35 dep residue 587:593 arg1 His 595:597 His 595:597 His 595:597 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 0 36 theme venom 26:30 arg1 oxidase 45:51 snake venom l-amino acid oxidase 20:51 snake venom l-amino acid oxidase 20:51 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 5 37 theme l-amino 985:991 arg1 substrates 998:1007 hydrophobic l-amino acid substrates 973:1007 hydrophobic l-amino acid substrates 973:1007 We find that NK-LAAO, with Ser 223, exhibits high catalytic activity toward hydrophobic l-amino acid substrates. 37385076 4 38 theme anticancer 804:813 arg1 potentials 827:836 the structural, biochemical, and anticancer therapeutic potentials 771:836 the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO) 771:894 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 0 39 theme acid 40:43 arg1 oxidase 45:51 snake venom l-amino acid oxidase 20:51 snake venom l-amino acid oxidase 20:51 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 6 40 link N-linked 1303:1310 arg1 glycans 1312:1318 the N-linked glycans 1299:1318 the N-linked glycans on its surface 1299:1333 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 8 41 theme -directed 1540:1548 arg1 pathway 1590:1596 the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway 1518:1596 the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway 1518:1596 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37385076 2 42 theme mechanism 325:333 arg1 aspects 298:304 multiple aspects 289:304 multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes 289:398 However, multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes remain ambiguous. 37385076 8 43 theme adaptive 1608:1615 arg1 phenotypes 1632:1641 adaptive and aggressive phenotypes 1608:1641 adaptive and aggressive phenotypes 1608:1641 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37385076 5 44 theme catalytic 947:955 arg1 activity 957:964 high catalytic activity 942:964 high catalytic activity toward hydrophobic l-amino acid substrates 942:1007 We find that NK-LAAO, with Ser 223, exhibits high catalytic activity toward hydrophobic l-amino acid substrates. 37385076 8 45 theme calcium 1564:1570 arg1 pathway 1590:1596 the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway 1518:1596 the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway 1518:1596 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37385076 3 46 theme svLAAO 657:662 arg1 clade 664:668 the viperid but not the elapid svLAAO clade 626:668 the viperid but not the elapid svLAAO clade 626:668 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 2 47 theme cancer 364:369 arg1 cells 371:375 cancer cells 364:375 cancer cells 364:375 However, multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes remain ambiguous. 37385076 8 48 theme aggressive 1621:1630 arg1 phenotypes 1632:1641 adaptive and aggressive phenotypes 1608:1641 adaptive and aggressive phenotypes 1608:1641 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37385076 10 49 theme Panx1/iCa2+/IL-6 1920:1935 arg1 axis 1937:1940 the Panx1/iCa2+/IL-6 axis 1916:1940 the Panx1/iCa2+/IL-6 axis 1916:1940 Collectively, our study urges caution when using svLAAOs in cancer treatment and identifies the Panx1/iCa2+/IL-6 axis as a therapeutic target for improving the effectiveness of svLAAOs-based anticancer therapies. 37385076 10 49 theme Panx1/iCa2+/IL-6 1920:1935 arg1 target 1959:1964 a therapeutic target 1945:1964 a therapeutic target for improving the effectiveness of svLAAOs-based anticancer therapies 1945:2034 Collectively, our study urges caution when using svLAAOs in cancer treatment and identifies the Panx1/iCa2+/IL-6 axis as a therapeutic target for improving the effectiveness of svLAAOs-based anticancer therapies. 37385076 2 50 theme responses 351:359 arg1 aspects 298:304 multiple aspects 289:304 multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes 289:398 However, multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes remain ambiguous. 37385076 1 51 theme promising 230:238 arg1 candidates 240:249 promising candidates 230:249 promising candidates for anticancer therapeutics 230:277 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 1 51 theme promising 230:238 arg1 oxidases 187:194 Snake venom l-amino acid oxidases 162:194 Snake venom l-amino acid oxidases (svLAAOs) 162:204 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 7 52 theme NK-LAAO 1447:1453 arg1 activities 1433:1442 the anticancer activities 1418:1442 the anticancer activities of NK-LAAO 1418:1453 Unexpectedly, we discover a tolerant mechanism deployed by cancer cells to dampen the anticancer activities of NK-LAAO. 37385076 4 53 theme Thailand 845:852 arg1 NK-LAAO 887:893 NK-LAAO 887:893 NK-LAAO 887:893 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 4 53 theme Thailand 845:852 arg1 LAAO 881:884 the Thailand elapid snake Naja kaouthia LAAO 841:884 the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO) 841:894 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 8 54 theme signaling 1580:1588 arg1 pathway 1590:1596 the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway 1518:1596 the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway 1518:1596 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37385076 4 55 theme snake 861:865 arg1 NK-LAAO 887:893 NK-LAAO 887:893 NK-LAAO 887:893 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 4 55 theme snake 861:865 arg1 LAAO 881:884 the Thailand elapid snake Naja kaouthia LAAO 841:884 the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO) 841:894 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 10 56 theme therapeutic 1947:1957 arg1 axis 1937:1940 the Panx1/iCa2+/IL-6 axis 1916:1940 the Panx1/iCa2+/IL-6 axis 1916:1940 Collectively, our study urges caution when using svLAAOs in cancer treatment and identifies the Panx1/iCa2+/IL-6 axis as a therapeutic target for improving the effectiveness of svLAAOs-based anticancer therapies. 37385076 10 56 theme therapeutic 1947:1957 arg1 target 1959:1964 a therapeutic target 1945:1964 a therapeutic target for improving the effectiveness of svLAAOs-based anticancer therapies 1945:2034 Collectively, our study urges caution when using svLAAOs in cancer treatment and identifies the Panx1/iCa2+/IL-6 axis as a therapeutic target for improving the effectiveness of svLAAOs-based anticancer therapies. 37385076 6 57 theme enzymatic 1244:1252 arg1 reactions 1260:1268 the enzymatic redox reactions 1240:1268 the enzymatic redox reactions 1240:1268 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 1 58 theme Snake 162:166 arg1 candidates 240:249 promising candidates 230:249 promising candidates for anticancer therapeutics 230:277 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 1 58 theme Snake 162:166 arg1 svLAAOs 197:203 svLAAOs 197:203 svLAAOs 197:203 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 1 58 theme Snake 162:166 arg1 oxidases 187:194 Snake venom l-amino acid oxidases 162:194 Snake venom l-amino acid oxidases (svLAAOs) 162:204 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 4 59 theme therapeutic 815:825 arg1 potentials 827:836 the structural, biochemical, and anticancer therapeutic potentials 771:836 the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO) 771:894 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 6 60 theme peroxide 1159:1166 arg1 levels 1126:1131 the levels 1122:1131 the levels of extracellular hydrogen peroxide (H2O2) 1122:1173 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 6 60 theme peroxide 1159:1166 arg1 ROS 1218:1220 ROS 1218:1220 ROS 1218:1220 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 6 60 theme peroxide 1159:1166 arg1 species 1209:1215 intracellular reactive oxygen species 1179:1215 intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions 1179:1268 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 3 61 theme critical 568:575 arg1 residue 587:593 the previously proposed critical catalytic residue 544:593 the previously proposed critical catalytic residue His 223 544:601 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 1 62 theme l-amino 174:180 arg1 candidates 240:249 promising candidates 230:249 promising candidates for anticancer therapeutics 230:277 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 1 62 theme l-amino 174:180 arg1 svLAAOs 197:203 svLAAOs 197:203 svLAAOs 197:203 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 1 62 theme l-amino 174:180 arg1 oxidases 187:194 Snake venom l-amino acid oxidases 162:194 Snake venom l-amino acid oxidases (svLAAOs) 162:204 Snake venom l-amino acid oxidases (svLAAOs) have been recognized as promising candidates for anticancer therapeutics. 37385076 8 63 theme IL 1497:1498 arg1 expression 1503:1512 interleukin (IL)-6 expression 1484:1512 interleukin (IL)-6 expression 1484:1512 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37385076 6 64 theme extracellular 1136:1148 arg1 H2O2 1169:1172 H2O2 1169:1172 H2O2 1169:1172 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 6 64 theme extracellular 1136:1148 arg1 peroxide 1159:1166 extracellular hydrogen peroxide 1136:1166 extracellular hydrogen peroxide (H2O2) 1136:1173 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 0 65 theme pannexin 116:123 arg1 expression 150:159 pannexin 1-mediated interleukin-6 expression 116:159 pannexin 1-mediated interleukin-6 expression 116:159 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 10 66 theme anticancer 2015:2024 arg1 therapies 2026:2034 svLAAOs-based anticancer therapies 2001:2034 svLAAOs-based anticancer therapies 2001:2034 Collectively, our study urges caution when using svLAAOs in cancer treatment and identifies the Panx1/iCa2+/IL-6 axis as a therapeutic target for improving the effectiveness of svLAAOs-based anticancer therapies. 37385076 0 67 theme interleukin-6 136:148 arg1 expression 150:159 pannexin 1-mediated interleukin-6 expression 116:159 pannexin 1-mediated interleukin-6 expression 116:159 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 4 68 theme kaouthia 872:879 arg1 NK-LAAO 887:893 NK-LAAO 887:893 NK-LAAO 887:893 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 4 68 theme kaouthia 872:879 arg1 LAAO 881:884 the Thailand elapid snake Naja kaouthia LAAO 841:884 the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO) 841:894 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 0 69 from treatment 97:105 arg1 mechanism 7:15 Action mechanism 0:15 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 0:160 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 6 70 theme reactive 1193:1200 arg1 ROS 1218:1220 ROS 1218:1220 ROS 1218:1220 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 6 70 theme reactive 1193:1200 arg1 species 1209:1215 intracellular reactive oxygen species 1179:1215 intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions 1179:1268 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 4 71 theme action 704:709 arg1 mechanism 711:719 the action mechanism 700:719 the action mechanism of the elapid svLAAOs 700:741 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 3 72 theme phylogenetic 454:465 arg1 relationships 467:479 the phylogenetic relationships 450:479 the phylogenetic relationships 450:479 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 9 73 theme NK-LAAO-induced 1723:1737 arg1 stress 1749:1754 NK-LAAO-induced oxidative stress 1723:1754 NK-LAAO-induced oxidative stress together with abrogating NK-LAAO-stimulated metastatic acquisition 1723:1821 Accordingly, IL-6 silencing renders cancer cells vulnerable to NK-LAAO-induced oxidative stress together with abrogating NK-LAAO-stimulated metastatic acquisition. 37385076 8 74 theme interleukin 1484:1494 arg1 IL 1497:1498 interleukin (IL)-6 1484:1501 interleukin (IL)-6 expression 1484:1512 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37385076 0 75 theme sword 74:78 arg1 effect 80:85 its double-edged sword effect 57:85 its double-edged sword effect on cancer treatment 57:105 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 0 76 from mechanism 7:15 arg1 treatment 97:105 cancer treatment 90:105 cancer treatment 90:105 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 10 77 theme cancer 1884:1889 arg1 treatment 1891:1899 cancer treatment 1884:1899 cancer treatment 1884:1899 Collectively, our study urges caution when using svLAAOs in cancer treatment and identifies the Panx1/iCa2+/IL-6 axis as a therapeutic target for improving the effectiveness of svLAAOs-based anticancer therapies. 37385076 4 78 theme further 679:685 arg1 insight 687:693 further insight 679:693 further insight into the action mechanism of the elapid svLAAOs 679:741 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 2 79 theme multiple 289:296 arg1 aspects 298:304 multiple aspects 289:304 multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes 289:398 However, multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes remain ambiguous. 37385076 0 80 from oxidase 45:51 arg1 treatment 97:105 cancer treatment 90:105 cancer treatment 90:105 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 3 81 theme relationships 467:479 arg1 analysis 438:445 an analysis 435:445 an analysis of the phylogenetic relationships and active site-related residues among svLAAOs 435:526 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 6 82 theme stress-mediated 1058:1072 arg1 cytotoxicity 1074:1085 substantial oxidative stress-mediated cytotoxicity 1036:1085 substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions 1036:1268 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 9 83 theme NK-LAAO-stimulated 1781:1798 arg1 acquisition 1811:1821 NK-LAAO-stimulated metastatic acquisition 1781:1821 NK-LAAO-stimulated metastatic acquisition 1781:1821 Accordingly, IL-6 silencing renders cancer cells vulnerable to NK-LAAO-induced oxidative stress together with abrogating NK-LAAO-stimulated metastatic acquisition. 37385076 6 84 theme substantial 1036:1046 arg1 cytotoxicity 1074:1085 substantial oxidative stress-mediated cytotoxicity 1036:1085 substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions 1036:1268 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 6 85 theme N-linked 1303:1310 arg1 glycans 1312:1318 the N-linked glycans 1299:1318 the N-linked glycans on its surface 1299:1333 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 2 86 theme cells 371:375 arg1 responses 351:359 the overall responses 339:359 the overall responses of cancer cells to these redox enzymes 339:398 However, multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes remain ambiguous. 37385076 2 86 theme cells 371:375 arg1 mechanism 325:333 their catalytic mechanism 309:333 their catalytic mechanism 309:333 However, multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes remain ambiguous. 37385076 0 87 theme snake 20:24 arg1 oxidase 45:51 snake venom l-amino acid oxidase 20:51 snake venom l-amino acid oxidase 20:51 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 4 88 theme elapid 728:733 arg1 svLAAOs 735:741 the elapid svLAAOs 724:741 the elapid svLAAOs 724:741 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 0 89 theme l-amino 32:38 arg1 oxidase 45:51 snake venom l-amino acid oxidase 20:51 snake venom l-amino acid oxidase 20:51 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 6 90 from glycans 1312:1318 arg1 surface 1327:1333 its surface 1323:1333 its surface 1323:1333 Moreover, NK-LAAO induces substantial oxidative stress-mediated cytotoxicity with the magnitude relying on both the levels of extracellular hydrogen peroxide (H2O2) and intracellular reactive oxygen species (ROS) generated during the enzymatic redox reactions, but not being influenced by the N-linked glycans on its surface. 37385076 5 91 theme hydrophobic 973:983 arg1 substrates 998:1007 hydrophobic l-amino acid substrates 973:1007 hydrophobic l-amino acid substrates 973:1007 We find that NK-LAAO, with Ser 223, exhibits high catalytic activity toward hydrophobic l-amino acid substrates. 37385076 3 92 theme viperid 630:636 arg1 clade 664:668 the viperid but not the elapid svLAAO clade 626:668 the viperid but not the elapid svLAAO clade 626:668 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 4 93 theme biochemical 787:797 arg1 potentials 827:836 the structural, biochemical, and anticancer therapeutic potentials 771:836 the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO) 771:894 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 0 94 theme oxidase 45:51 arg1 mechanism 7:15 Action mechanism 0:15 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 0:160 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 5 95 theme acid 993:996 arg1 substrates 998:1007 hydrophobic l-amino acid substrates 973:1007 hydrophobic l-amino acid substrates 973:1007 We find that NK-LAAO, with Ser 223, exhibits high catalytic activity toward hydrophobic l-amino acid substrates. 37385076 8 96 theme intracellular 1550:1562 arg1 iCa2+ 1573:1577 iCa2+ 1573:1577 iCa2+ 1573:1577 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37385076 8 96 theme intracellular 1550:1562 arg1 calcium 1564:1570 intracellular calcium 1550:1570 the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway 1518:1596 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37385076 3 97 theme residues 505:512 arg1 analysis 438:445 an analysis 435:445 an analysis of the phylogenetic relationships and active site-related residues among svLAAOs 435:526 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 3 98 theme active 485:490 arg1 residues 505:512 active site-related residues 485:512 active site-related residues 485:512 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 5 99 theme high 942:945 arg1 activity 957:964 high catalytic activity 942:964 high catalytic activity toward hydrophobic l-amino acid substrates 942:1007 We find that NK-LAAO, with Ser 223, exhibits high catalytic activity toward hydrophobic l-amino acid substrates. 37385076 3 100 theme elapid 650:655 arg1 clade 664:668 the viperid but not the elapid svLAAO clade 626:668 the viperid but not the elapid svLAAO clade 626:668 Here, we present an analysis of the phylogenetic relationships and active site-related residues among svLAAOs and reveal that the previously proposed critical catalytic residue His 223 is highly conserved in the viperid but not the elapid svLAAO clade. 37385076 2 101 theme catalytic 315:323 arg1 mechanism 325:333 their catalytic mechanism 309:333 their catalytic mechanism 309:333 However, multiple aspects of their catalytic mechanism and the overall responses of cancer cells to these redox enzymes remain ambiguous. 37385076 0 102 dep mechanism 7:15 arg1 Role 108:111 Role 108:111 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 0:160 Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression. 37385076 4 103 theme structural 775:784 arg1 potentials 827:836 the structural, biochemical, and anticancer therapeutic potentials 771:836 the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO) 771:894 To gain further insight into the action mechanism of the elapid svLAAOs, we purify and characterize the structural, biochemical, and anticancer therapeutic potentials of the Thailand elapid snake Naja kaouthia LAAO (NK-LAAO). 37385076 8 104 theme cancer 1646:1651 arg1 cells 1653:1657 cancer cells 1646:1657 cancer cells 1646:1657 NK-LAAO treatment amplifies interleukin (IL)-6 expression via the pannexin 1 (Panx1)-directed intracellular calcium (iCa2+) signaling pathway to confer adaptive and aggressive phenotypes on cancer cells. 37180248 4 0 theme microbial 510:518 arg1 community 520:528 the root microbial community 501:528 the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency 501:721 In this study, we analyzed the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency. 37180248 11 1 from rhizocompartments 2042:2058 arg1 transformation 2094:2107 nutrient transformation 2085:2107 nutrient transformation 2085:2107 Soil sterilization might remove these beneficial microbes from the bulk soil pool, affecting the colonization ability in the rhizocompartments as well as their role in nutrient transformation. 37180248 9 2 theme sequence 1520:1527 arg1 ASVs 1540:1543 ASVs 1540:1543 ASVs 1540:1543 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 9 2 theme sequence 1520:1527 arg1 variances 1529:1537 412 and 868 amplicon sequence variances 1499:1537 412 and 868 amplicon sequence variances (ASVs) 1499:1544 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 7 3 theme microbiota 1290:1299 arg1 composition 1301:1311 the soil microbiota composition 1281:1311 the soil microbiota composition 1281:1311 After autoclaving, the soil macronutrient content did not change, but soil sterilization reduced microbial diversity in the +FS and -FS treatments and altered the soil microbiota composition. 37180248 2 4 theme soil 267:270 arg1 microbiota 272:281 soil microbiota 267:281 soil microbiota 267:281 However, limited studies have been conducted on the importance of soil microbiota in the early growth of oil palm seedlings (Elaeis guineensis Jacq.) 37180248 6 5 theme Bacteroidota 1037:1048 arg1 growth 992:997 the growth 988:997 the growth of the copiotrophs Pseudomonadota and Bacteroidota 988:1048 Our findings revealed that chemical fertilizer promoted the growth of the copiotrophs Pseudomonadota and Bacteroidota in the control +FN, which are known to degrade complex polysaccharides. 37180248 2 6 dep conducted 236:244 arg1 Jacq 344:347 Jacq 344:347 Jacq 344:347 However, limited studies have been conducted on the importance of soil microbiota in the early growth of oil palm seedlings (Elaeis guineensis Jacq.) 37180248 5 7 dep soil 920:923 arg1 iv 892:893 iv 892:893 iv 892:893 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 1 8 theme plant 165:169 arg1 growth 171:176 healthy plant growth 157:176 healthy plant growth 157:176 Soil nutrients and microbiota are known as essential components for healthy plant growth and crop productivity. 37180248 11 9 theme bulk 1984:1987 arg1 pool 1994:1997 the bulk soil pool 1980:1997 the bulk soil pool 1980:1997 Soil sterilization might remove these beneficial microbes from the bulk soil pool, affecting the colonization ability in the rhizocompartments as well as their role in nutrient transformation. 37180248 6 10 theme Pseudomonadota 1018:1031 arg1 growth 992:997 the growth 988:997 the growth of the copiotrophs Pseudomonadota and Bacteroidota 988:1048 Our findings revealed that chemical fertilizer promoted the growth of the copiotrophs Pseudomonadota and Bacteroidota in the control +FN, which are known to degrade complex polysaccharides. 37180248 6 11 dep Pseudomonadota 1018:1031 arg1 the 1002:1004 the 1002:1004 the 1002:1004 Our findings revealed that chemical fertilizer promoted the growth of the copiotrophs Pseudomonadota and Bacteroidota in the control +FN, which are known to degrade complex polysaccharides. 37180248 6 12 theme complex 1097:1103 arg1 polysaccharides 1105:1119 complex polysaccharides 1097:1119 complex polysaccharides 1097:1119 Our findings revealed that chemical fertilizer promoted the growth of the copiotrophs Pseudomonadota and Bacteroidota in the control +FN, which are known to degrade complex polysaccharides. 37180248 2 13 theme early 290:294 arg1 growth 296:301 the early growth 286:301 the early growth of oil palm seedlings 286:323 However, limited studies have been conducted on the importance of soil microbiota in the early growth of oil palm seedlings (Elaeis guineensis Jacq.) 37180248 7 14 theme -FS 1254:1256 arg1 treatments 1258:1267 the +FS and -FS treatments 1242:1267 treatments 1258:1267 After autoclaving, the soil macronutrient content did not change, but soil sterilization reduced microbial diversity in the +FS and -FS treatments and altered the soil microbiota composition. 37180248 10 15 theme several 1803:1809 arg1 genera 1824:1829 several unclassified genera 1803:1829 several unclassified genera 1803:1829 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 5 16 theme normal 829:834 arg1 -FN 842:844 -FN 842:844 -FN 842:844 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 16 theme normal 829:834 arg1 soil 836:839 unfertilized normal soil 816:839 (ii) unfertilized normal soil (-FN) 811:845 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 16 theme normal 829:834 arg1 soil 799:802 normal soil 792:802 normal soil (+FN) 792:808 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 12 17 theme soil 2186:2189 arg1 survey 2202:2207 a soil microbiome survey 2184:2207 a soil microbiome survey 2184:2207 Therefore, this study provides useful insights concerning the benefits of a soil microbiome survey before making fertilizer recommendations. 37180248 7 18 theme +FS 1246:1248 arg1 treatments 1258:1267 the +FS and -FS treatments 1242:1267 treatments 1258:1267 After autoclaving, the soil macronutrient content did not change, but soil sterilization reduced microbial diversity in the +FS and -FS treatments and altered the soil microbiota composition. 37180248 4 19 theme soil 590:593 arg1 conditions 595:604 normal and sterilized soil conditions 568:604 normal and sterilized soil conditions 568:604 In this study, we analyzed the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency. 37180248 10 20 theme possible 1849:1856 arg1 roles 1858:1862 their possible roles 1843:1862 their possible roles in promoting the plant growth of oil palm seedlings 1843:1914 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 5 21 theme normal 792:797 arg1 soil 836:839 unfertilized normal soil 816:839 (ii) unfertilized normal soil (-FN) 811:845 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 21 theme normal 792:797 arg1 +FN 805:807 +FN 805:807 +FN 805:807 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 21 theme normal 792:797 arg1 soil 799:802 normal soil 792:802 normal soil (+FN) 792:808 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 12 22 theme survey 2202:2207 arg1 benefits 2172:2179 the benefits 2168:2179 the benefits of a soil microbiome survey 2168:2207 Therefore, this study provides useful insights concerning the benefits of a soil microbiome survey before making fertilizer recommendations. 37180248 5 23 theme unfertilized 896:907 arg1 soil 920:923 unfertilized sterilized soil 896:923 (iv) unfertilized sterilized soil (-FS) 891:929 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 23 theme unfertilized 896:907 arg1 -FS 926:928 -FS 926:928 -FS 926:928 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 9 24 located found 1551:1555 arg1 compartments 1474:1485 the rhizosphere and rhizoplane compartments 1443:1485 compartments 1474:1485 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 9 24 located found 1551:1555 arg2 total 1490:1494 a total 1488:1494 a total of 412 and 868 amplicon sequence variances (ASVs) 1488:1544 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 7 25 theme microbial 1219:1227 arg1 diversity 1229:1237 microbial diversity 1219:1237 microbial diversity in the +FS and -FS treatments 1219:1267 After autoclaving, the soil macronutrient content did not change, but soil sterilization reduced microbial diversity in the +FS and -FS treatments and altered the soil microbiota composition. 37180248 4 26 theme plant 675:679 arg1 health 681:686 plant health 675:686 plant health 675:686 In this study, we analyzed the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency. 37180248 9 27 theme rhizosphere 1447:1457 arg1 compartments 1474:1485 the rhizosphere and rhizoplane compartments 1443:1485 compartments 1474:1485 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 10 28 theme Several 1611:1617 arg1 genera 1619:1624 Several genera 1611:1624 Several genera 1611:1624 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 8 29 theme microbial 1346:1354 arg1 population 1356:1365 a depleted microbial population 1335:1365 a depleted microbial population 1335:1365 Sterilized soil with a depleted microbial population adversely affected crop growth, which was exacerbated by fertilizer use. 37180248 1 30 theme essential 132:140 arg1 components 142:151 essential components 132:151 essential components for healthy plant growth and crop productivity 132:198 Soil nutrients and microbiota are known as essential components for healthy plant growth and crop productivity. 37180248 1 30 theme essential 132:140 arg1 microbiota 108:117 microbiota 108:117 microbiota 108:117 Soil nutrients and microbiota are known as essential components for healthy plant growth and crop productivity. 37180248 1 30 theme essential 132:140 arg1 nutrients 94:102 Soil nutrients 89:102 Soil nutrients 89:102 Soil nutrients and microbiota are known as essential components for healthy plant growth and crop productivity. 37180248 10 31 theme oil 1897:1899 arg1 seedlings 1906:1914 oil palm seedlings 1897:1914 oil palm seedlings 1897:1914 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 0 32 theme oil 69:71 arg1 seedlings 78:86 oil palm seedlings 69:86 oil palm seedlings 69:86 Impact of sterilization and chemical fertilizer on the microbiota of oil palm seedlings. 37180248 9 33 theme variances 1529:1537 arg1 total 1490:1494 a total 1488:1494 a total of 412 and 868 amplicon sequence variances (ASVs) 1488:1544 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 0 34 from Impact 0:5 arg1 microbiota 55:64 the microbiota 51:64 the microbiota of oil palm seedlings 51:86 Impact of sterilization and chemical fertilizer on the microbiota of oil palm seedlings. 37180248 5 35 dep soil 836:839 arg1 ii 812:813 ii 812:813 ii 812:813 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 0 36 theme seedlings 78:86 arg1 microbiota 55:64 the microbiota 51:64 the microbiota of oil palm seedlings 51:86 Impact of sterilization and chemical fertilizer on the microbiota of oil palm seedlings. 37180248 3 37 dep nitrogen 436:443 arg1 influence 361:369 the influence 357:369 the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer 357:433 under the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer (nitrogen, phosphorus, and potassium). 37180248 3 38 theme potassium 399:407 arg1 fertilizer 424:433 potassium (NPK) compound fertilizer 399:433 potassium (NPK) compound fertilizer 399:433 under the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer (nitrogen, phosphorus, and potassium). 37180248 5 39 theme sterilized 865:874 arg1 +FS 882:884 +FS 882:884 +FS 882:884 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 39 theme sterilized 865:874 arg1 soil 876:879 sterilized soil 865:879 sterilized soil (+FS) 865:885 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 7 40 theme soil 1192:1195 arg1 sterilization 1197:1209 soil sterilization 1192:1209 soil sterilization 1192:1209 After autoclaving, the soil macronutrient content did not change, but soil sterilization reduced microbial diversity in the +FS and -FS treatments and altered the soil microbiota composition. 37180248 11 41 theme colonization 2014:2025 arg1 ability 2027:2033 the colonization ability 2010:2033 the colonization ability 2010:2033 Soil sterilization might remove these beneficial microbes from the bulk soil pool, affecting the colonization ability in the rhizocompartments as well as their role in nutrient transformation. 37180248 3 42 theme phosphorus 384:393 arg1 influence 361:369 the influence 357:369 the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer 357:433 under the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer (nitrogen, phosphorus, and potassium). 37180248 4 43 theme fertilizer 701:710 arg1 efficiency 712:721 chemical fertilizer efficiency 692:721 chemical fertilizer efficiency 692:721 In this study, we analyzed the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency. 37180248 3 44 theme compound 415:422 arg1 fertilizer 424:433 potassium (NPK) compound fertilizer 399:433 potassium (NPK) compound fertilizer 399:433 under the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer (nitrogen, phosphorus, and potassium). 37180248 0 45 theme sterilization 10:22 arg1 Impact 0:5 Impact 0:5 Impact of sterilization and chemical fertilizer on the microbiota of oil palm seedlings. 0:87 Impact of sterilization and chemical fertilizer on the microbiota of oil palm seedlings. 37180248 9 46 dep found 1551:1555 arg1 depleted 1557:1564 depleted 1557:1564 depleted 1557:1564 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 3 47 theme nitrogen 374:381 arg1 influence 361:369 the influence 357:369 the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer 357:433 under the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer (nitrogen, phosphorus, and potassium). 37180248 3 48 theme NPK 410:412 arg1 fertilizer 424:433 potassium (NPK) compound fertilizer 399:433 potassium (NPK) compound fertilizer 399:433 under the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer (nitrogen, phosphorus, and potassium). 37180248 0 49 theme chemical 28:35 arg1 fertilizer 37:46 chemical fertilizer 28:46 chemical fertilizer 28:46 Impact of sterilization and chemical fertilizer on the microbiota of oil palm seedlings. 37180248 2 50 theme seedlings 315:323 arg1 growth 296:301 the early growth 286:301 the early growth of oil palm seedlings 286:323 However, limited studies have been conducted on the importance of soil microbiota in the early growth of oil palm seedlings (Elaeis guineensis Jacq.) 37180248 7 51 theme soil 1145:1148 arg1 content 1164:1170 the soil macronutrient content 1141:1170 the soil macronutrient content 1141:1170 After autoclaving, the soil macronutrient content did not change, but soil sterilization reduced microbial diversity in the +FS and -FS treatments and altered the soil microbiota composition. 37180248 5 52 dep fertilized 781:790 arg1 i 778:778 i 778:778 i 778:778 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 52 dep fertilized 781:790 arg1 fertilized 854:863 fertilized 854:863 fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS) 854:929 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 52 dep fertilized 781:790 arg1 iii 849:851 iii 849:851 iii 849:851 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 2 53 theme oil 306:308 arg1 seedlings 315:323 oil palm seedlings 306:323 oil palm seedlings 306:323 However, limited studies have been conducted on the importance of soil microbiota in the early growth of oil palm seedlings (Elaeis guineensis Jacq.) 37180248 10 54 theme seedlings 1906:1914 arg1 growth 1887:1892 the plant growth 1877:1892 the plant growth of oil palm seedlings 1877:1914 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 11 55 from role 2077:2080 arg1 transformation 2094:2107 nutrient transformation 2085:2107 nutrient transformation 2085:2107 Soil sterilization might remove these beneficial microbes from the bulk soil pool, affecting the colonization ability in the rhizocompartments as well as their role in nutrient transformation. 37180248 5 56 theme Oil 724:726 arg1 seedlings 733:741 Oil palm seedlings 724:741 Oil palm seedlings 724:741 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 9 57 theme amplicon 1511:1518 arg1 ASVs 1540:1543 ASVs 1540:1543 ASVs 1540:1543 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 9 57 theme amplicon 1511:1518 arg1 variances 1529:1537 412 and 868 amplicon sequence variances 1499:1537 412 and 868 amplicon sequence variances (ASVs) 1499:1544 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 4 58 theme root 505:508 arg1 community 520:528 the root microbial community 501:528 the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency 501:721 In this study, we analyzed the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency. 37180248 2 59 theme microbiota 272:281 arg1 importance 253:262 the importance 249:262 the importance of soil microbiota in the early growth of oil palm seedlings 249:323 However, limited studies have been conducted on the importance of soil microbiota in the early growth of oil palm seedlings (Elaeis guineensis Jacq.) 37180248 5 60 dep treatments 765:774 arg1 fertilized 781:790 fertilized 781:790 fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN) 781:845 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 1 61 theme healthy 157:163 arg1 growth 171:176 healthy plant growth 157:176 healthy plant growth 157:176 Soil nutrients and microbiota are known as essential components for healthy plant growth and crop productivity. 37180248 7 62 theme soil 1285:1288 arg1 composition 1301:1311 the soil microbiota composition 1281:1311 the soil microbiota composition 1281:1311 After autoclaving, the soil macronutrient content did not change, but soil sterilization reduced microbial diversity in the +FS and -FS treatments and altered the soil microbiota composition. 37180248 5 63 theme palm 728:731 arg1 seedlings 733:741 Oil palm seedlings 724:741 Oil palm seedlings 724:741 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 10 64 with ASVs 1649:1652 arg1 abundance 1670:1678 diminished abundance 1659:1678 diminished abundance 1659:1678 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 11 65 theme soil 1989:1992 arg1 pool 1994:1997 the bulk soil pool 1980:1997 the bulk soil pool 1980:1997 Soil sterilization might remove these beneficial microbes from the bulk soil pool, affecting the colonization ability in the rhizocompartments as well as their role in nutrient transformation. 37180248 10 66 theme unclassified 1811:1822 arg1 genera 1824:1829 several unclassified genera 1803:1829 several unclassified genera 1803:1829 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 1 67 theme crop 182:185 arg1 productivity 187:198 crop productivity 182:198 crop productivity 182:198 Soil nutrients and microbiota are known as essential components for healthy plant growth and crop productivity. 37180248 11 68 theme Soil 1917:1920 arg1 sterilization 1922:1934 Soil sterilization 1917:1934 Soil sterilization 1917:1934 Soil sterilization might remove these beneficial microbes from the bulk soil pool, affecting the colonization ability in the rhizocompartments as well as their role in nutrient transformation. 37180248 8 69 theme Sterilized 1314:1323 arg1 soil 1325:1328 Sterilized soil 1314:1328 Sterilized soil with a depleted microbial population 1314:1365 Sterilized soil with a depleted microbial population adversely affected crop growth, which was exacerbated by fertilizer use. 37180248 4 70 theme normal 568:573 arg1 conditions 595:604 normal and sterilized soil conditions 568:604 normal and sterilized soil conditions 568:604 In this study, we analyzed the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency. 37180248 2 71 theme palm 310:313 arg1 seedlings 315:323 oil palm seedlings 306:323 oil palm seedlings 306:323 However, limited studies have been conducted on the importance of soil microbiota in the early growth of oil palm seedlings (Elaeis guineensis Jacq.) 37180248 10 72 theme diminished 1659:1668 arg1 abundance 1670:1678 diminished abundance 1659:1678 diminished abundance 1659:1678 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 4 73 theme sterilized 579:588 arg1 conditions 595:604 normal and sterilized soil conditions 568:604 normal and sterilized soil conditions 568:604 In this study, we analyzed the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency. 37180248 2 74 theme limited 210:216 arg1 studies 218:224 limited studies 210:224 limited studies 210:224 However, limited studies have been conducted on the importance of soil microbiota in the early growth of oil palm seedlings (Elaeis guineensis Jacq.) 37180248 5 75 theme unfertilized 816:827 arg1 -FN 842:844 -FN 842:844 -FN 842:844 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 75 theme unfertilized 816:827 arg1 soil 836:839 unfertilized normal soil 816:839 (ii) unfertilized normal soil (-FN) 811:845 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 75 theme unfertilized 816:827 arg1 soil 799:802 normal soil 792:802 normal soil (+FN) 792:808 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 8 76 theme crop 1386:1389 arg1 growth 1391:1396 crop growth 1386:1396 crop growth 1386:1396 Sterilized soil with a depleted microbial population adversely affected crop growth, which was exacerbated by fertilizer use. 37180248 8 77 theme depleted 1337:1344 arg1 population 1356:1365 a depleted microbial population 1335:1365 a depleted microbial population 1335:1365 Sterilized soil with a depleted microbial population adversely affected crop growth, which was exacerbated by fertilizer use. 37180248 5 78 theme sterilized 909:918 arg1 soil 920:923 unfertilized sterilized soil 896:923 (iv) unfertilized sterilized soil (-FS) 891:929 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 5 78 theme sterilized 909:918 arg1 -FS 926:928 -FS 926:928 -FS 926:928 Oil palm seedlings were grown under four treatments: (i) fertilized normal soil (+FN), (ii) unfertilized normal soil (-FN), (iii) fertilized sterilized soil (+FS) and (iv) unfertilized sterilized soil (-FS). 37180248 10 79 theme Humibacter 1691:1700 arg1 1921-2 1734:1739 Humibacter, Microbacterium, Mycobacterium, 1921-2 1691:1739 1921-2 1734:1739 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 10 79 theme Humibacter 1691:1700 arg1 Microbacterium 1703:1716 Microbacterium 1703:1716 Microbacterium 1703:1716 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 2 80 from importance 253:262 arg1 growth 296:301 the early growth 286:301 the early growth of oil palm seedlings 286:323 However, limited studies have been conducted on the importance of soil microbiota in the early growth of oil palm seedlings (Elaeis guineensis Jacq.) 37180248 12 81 theme useful 2141:2146 arg1 insights 2148:2155 useful insights 2141:2155 useful insights concerning the benefits of a soil microbiome survey before making fertilizer recommendations 2141:2248 Therefore, this study provides useful insights concerning the benefits of a soil microbiome survey before making fertilizer recommendations. 37180248 6 82 theme control 1057:1063 arg1 +FN 1065:1067 the control +FN 1053:1067 the control +FN 1053:1067 Our findings revealed that chemical fertilizer promoted the growth of the copiotrophs Pseudomonadota and Bacteroidota in the control +FN, which are known to degrade complex polysaccharides. 37180248 4 83 theme microbial 623:631 arg1 strains 633:639 the microbial strains 619:639 the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency 619:721 In this study, we analyzed the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency. 37180248 0 84 theme palm 73:76 arg1 seedlings 78:86 oil palm seedlings 69:86 oil palm seedlings 69:86 Impact of sterilization and chemical fertilizer on the microbiota of oil palm seedlings. 37180248 12 85 theme fertilizer 2223:2232 arg1 recommendations 2234:2248 fertilizer recommendations 2223:2248 fertilizer recommendations 2223:2248 Therefore, this study provides useful insights concerning the benefits of a soil microbiome survey before making fertilizer recommendations. 37180248 12 86 theme microbiome 2191:2200 arg1 survey 2202:2207 a soil microbiome survey 2184:2207 a soil microbiome survey 2184:2207 Therefore, this study provides useful insights concerning the benefits of a soil microbiome survey before making fertilizer recommendations. 37180248 10 87 theme plant 1881:1885 arg1 growth 1887:1892 the plant growth 1877:1892 the plant growth of oil palm seedlings 1877:1914 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 9 88 dep +FS 1573:1575 arg1 the 1569:1571 the 1569:1571 the 1569:1571 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 9 88 dep +FS 1573:1575 arg1 treatments 1585:1594 treatments 1585:1594 treatments 1585:1594 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 11 89 theme nutrient 2085:2092 arg1 transformation 2094:2107 nutrient transformation 2085:2107 nutrient transformation 2085:2107 Soil sterilization might remove these beneficial microbes from the bulk soil pool, affecting the colonization ability in the rhizocompartments as well as their role in nutrient transformation. 37180248 7 90 from diversity 1229:1237 arg1 treatments 1258:1267 the +FS and -FS treatments 1242:1267 treatments 1258:1267 After autoclaving, the soil macronutrient content did not change, but soil sterilization reduced microbial diversity in the +FS and -FS treatments and altered the soil microbiota composition. 37180248 8 91 theme fertilizer 1424:1433 arg1 use 1435:1437 fertilizer use 1424:1437 fertilizer use 1424:1437 Sterilized soil with a depleted microbial population adversely affected crop growth, which was exacerbated by fertilizer use. 37180248 1 92 theme Soil 89:92 arg1 components 142:151 essential components 132:151 essential components for healthy plant growth and crop productivity 132:198 Soil nutrients and microbiota are known as essential components for healthy plant growth and crop productivity. 37180248 1 92 theme Soil 89:92 arg1 microbiota 108:117 microbiota 108:117 microbiota 108:117 Soil nutrients and microbiota are known as essential components for healthy plant growth and crop productivity. 37180248 1 92 theme Soil 89:92 arg1 nutrients 94:102 Soil nutrients 89:102 Soil nutrients 89:102 Soil nutrients and microbiota are known as essential components for healthy plant growth and crop productivity. 37180248 4 93 theme chemical 692:699 arg1 efficiency 712:721 chemical fertilizer efficiency 692:721 chemical fertilizer efficiency 692:721 In this study, we analyzed the root microbial community associated with seedlings grown under normal and sterilized soil conditions to ascertain the microbial strains potentially associated with soil, plant health and chemical fertilizer efficiency. 37180248 3 94 theme fertilizer 424:433 arg1 influence 361:369 the influence 357:369 the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer 357:433 under the influence of nitrogen, phosphorus and potassium (NPK) compound fertilizer (nitrogen, phosphorus, and potassium). 37180248 0 95 theme fertilizer 37:46 arg1 Impact 0:5 Impact 0:5 Impact of sterilization and chemical fertilizer on the microbiota of oil palm seedlings. 0:87 Impact of sterilization and chemical fertilizer on the microbiota of oil palm seedlings. 37180248 9 96 theme rhizoplane 1463:1472 arg1 compartments 1474:1485 the rhizosphere and rhizoplane compartments 1443:1485 compartments 1474:1485 In the rhizosphere and rhizoplane compartments, a total of 412 and 868 amplicon sequence variances (ASVs) were found depleted in the +FS and -FS treatments, respectively. 37180248 7 97 theme macronutrient 1150:1162 arg1 content 1164:1170 the soil macronutrient content 1141:1170 the soil macronutrient content 1141:1170 After autoclaving, the soil macronutrient content did not change, but soil sterilization reduced microbial diversity in the +FS and -FS treatments and altered the soil microbiota composition. 37180248 11 98 theme beneficial 1955:1964 arg1 microbes 1966:1973 these beneficial microbes 1949:1973 these beneficial microbes 1949:1973 Soil sterilization might remove these beneficial microbes from the bulk soil pool, affecting the colonization ability in the rhizocompartments as well as their role in nutrient transformation. 37180248 8 99 with soil 1325:1328 arg1 population 1356:1365 a depleted microbial population 1335:1365 a depleted microbial population 1335:1365 Sterilized soil with a depleted microbial population adversely affected crop growth, which was exacerbated by fertilizer use. 37180248 10 100 dep 1921-2 1734:1739 arg1 Mycobacterium 1719:1731 Humibacter, Microbacterium, Mycobacterium, 1921-2 1691:1739 Mycobacterium 1719:1731 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 10 100 dep 1921-2 1734:1739 arg1 Bacillus 1774:1781 Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera 1691:1829 Bacillus 1774:1781 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 37180248 6 101 theme chemical 959:966 arg1 fertilizer 968:977 chemical fertilizer 959:977 chemical fertilizer 959:977 Our findings revealed that chemical fertilizer promoted the growth of the copiotrophs Pseudomonadota and Bacteroidota in the control +FN, which are known to degrade complex polysaccharides. 37180248 10 102 theme palm 1901:1904 arg1 seedlings 1906:1914 oil palm seedlings 1897:1914 oil palm seedlings 1897:1914 Several genera were identified in the ASVs with diminished abundance, including Humibacter, Microbacterium, Mycobacterium, 1921-2, HSB OF53-F07, Mucilaginibacter, Bacillus, Paenibacillus, and several unclassified genera, suggesting their possible roles in promoting the plant growth of oil palm seedlings. 36832926 0 0 theme Spray 61:65 arg1 Drying 67:72 Spray Drying 61:72 Spray Drying 61:72 A New Functional Food Ingredient Obtained from Aloe ferox by Spray Drying. 36832926 4 1 theme DPPH 662:665 arg1 methods 667:673 both ABTS and DPPH methods 648:673 methods 667:673 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 1 2 theme Aloe 119:122 arg1 vera 124:127 Aloe vera 119:127 Aloe vera (A. vera) 119:137 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 1 2 theme Aloe 119:122 arg1 vera 133:136 A. vera 130:136 A. vera 130:136 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 5 3 theme fat 952:954 arg1 capacities 967:976 fat adsorption capacities 952:976 fat adsorption capacities 952:976 Further, FP, such as swelling, increased around 25% when A. ferox was spray-dried at 160 °C, while water retention and fat adsorption capacities exhibited lower values when the drying temperature increased. 36832926 6 4 theme mannan 1072:1077 arg1 occurrence 1044:1053 The occurrence 1040:1053 The occurrence of an acetylated mannan with a high degree of acetylation 1040:1111 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 1 5 theme antioxidant 245:255 arg1 capacity 257:264 antioxidant capacity 245:264 antioxidant capacity 245:264 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 5 6 theme adsorption 956:965 arg1 capacities 967:976 fat adsorption capacities 952:976 fat adsorption capacities 952:976 Further, FP, such as swelling, increased around 25% when A. ferox was spray-dried at 160 °C, while water retention and fat adsorption capacities exhibited lower values when the drying temperature increased. 36832926 6 7 theme acetylated 1061:1070 arg1 mannan 1072:1077 an acetylated mannan 1058:1077 an acetylated mannan with a high degree of acetylation 1058:1111 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 2 8 theme mucilages 404:412 arg1 % 391:391 >70% 388:391 >70% of SD aloe mucilages 388:412 A. ferox polysaccharides were comprised mainly of mannose, accounting for >70% of SD aloe mucilages; similar results were observed for A. vera. 36832926 2 8 theme mucilages 404:412 arg1 mucilages 404:412 SD aloe mucilages 396:412 SD aloe mucilages 396:412 A. ferox polysaccharides were comprised mainly of mannose, accounting for >70% of SD aloe mucilages; similar results were observed for A. vera. 36832926 4 9 dep increased 570:578 arg1 whereas 728:734 whereas 728:734 whereas 728:734 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 2 10 theme aloe 399:402 arg1 mucilages 404:412 SD aloe mucilages 396:412 SD aloe mucilages 396:412 A. ferox polysaccharides were comprised mainly of mannose, accounting for >70% of SD aloe mucilages; similar results were observed for A. vera. 36832926 1 11 from composition 200:210 arg1 spray-dried 144:154 spray-dried 144:154 spray-dried 144:154 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 4 12 theme antioxidant 603:613 arg1 capacity 615:622 the antioxidant capacity 599:622 the antioxidant capacity of A. ferox 599:634 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 5 13 theme lower 988:992 arg1 values 994:999 lower values 988:999 lower values 988:999 Further, FP, such as swelling, increased around 25% when A. ferox was spray-dried at 160 °C, while water retention and fat adsorption capacities exhibited lower values when the drying temperature increased. 36832926 1 14 theme vera 124:127 arg1 mucilages 80:88 Aloe mucilages 75:88 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) 75:137 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 2 15 theme SD 396:397 arg1 mucilages 404:412 SD aloe mucilages 396:412 SD aloe mucilages 396:412 A. ferox polysaccharides were comprised mainly of mannose, accounting for >70% of SD aloe mucilages; similar results were observed for A. vera. 36832926 1 16 theme functional 270:279 arg1 FP 293:294 FP 293:294 FP 293:294 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 1 16 theme functional 270:279 arg1 properties 281:290 functional properties 270:290 functional properties (FP) 270:295 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 4 17 dep reduced 794:800 arg1 % 806:806 >20% 803:806 >20% 803:806 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 0 18 theme New 2:4 arg1 Ingredient 22:31 A New Functional Food Ingredient 0:31 A New Functional Food Ingredient 0:31 A New Functional Food Ingredient Obtained from Aloe ferox by Spray Drying. 36832926 6 19 theme high 1086:1089 arg1 degree 1091:1096 a high degree 1084:1096 a high degree of acetylation 1084:1111 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 20 theme raw 1221:1223 arg1 material 1225:1232 a valuable alternative raw material 1198:1232 a valuable alternative raw material 1198:1232 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 20 theme raw 1221:1223 arg1 ferox 1183:1187 SD A. ferox 1177:1187 SD A. ferox 1177:1187 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 1 21 theme A. 130:131 arg1 vera 124:127 Aloe vera 119:127 Aloe vera (A. vera) 119:137 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 1 21 theme A. 130:131 arg1 vera 133:136 A. vera 130:136 A. vera 130:136 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 6 22 theme enhanced 1132:1139 arg1 capacity 1153:1160 the enhanced antioxidant capacity 1128:1160 the enhanced antioxidant capacity 1128:1160 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 1 23 theme °C. 181:183 arg1 composition 200:210 150, 160 and 170 °C. Polysaccharide composition 164:210 150, 160 and 170 °C. Polysaccharide composition 164:210 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 1 24 theme Aloe 75:78 arg1 mucilages 80:88 Aloe mucilages 75:88 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) 75:137 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 6 25 theme alternative 1209:1219 arg1 material 1225:1232 a valuable alternative raw material 1198:1232 a valuable alternative raw material 1198:1232 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 25 theme alternative 1209:1219 arg1 ferox 1183:1187 SD A. ferox 1177:1187 SD A. ferox 1177:1187 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 0 26 theme Food 17:20 arg1 Ingredient 22:31 A New Functional Food Ingredient 0:31 A New Functional Food Ingredient 0:31 A New Functional Food Ingredient Obtained from Aloe ferox by Spray Drying. 36832926 1 27 theme Polysaccharide 185:198 arg1 composition 200:210 150, 160 and 170 °C. Polysaccharide composition 164:210 150, 160 and 170 °C. Polysaccharide composition 164:210 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 6 28 theme Aloe 1298:1301 arg1 plants 1303:1308 Aloe plants 1298:1308 Aloe plants 1298:1308 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 29 theme valuable 1200:1207 arg1 material 1225:1232 a valuable alternative raw material 1198:1232 a valuable alternative raw material 1198:1232 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 29 theme valuable 1200:1207 arg1 ferox 1183:1187 SD A. ferox 1177:1187 SD A. ferox 1177:1187 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 2 30 theme ferox 317:321 arg1 polysaccharides 323:337 A. ferox polysaccharides 314:337 A. ferox polysaccharides 314:337 A. ferox polysaccharides were comprised mainly of mannose, accounting for >70% of SD aloe mucilages; similar results were observed for A. vera. 36832926 0 31 theme Functional 6:15 arg1 Ingredient 22:31 A New Functional Food Ingredient 0:31 A New Functional Food Ingredient 0:31 A New Functional Food Ingredient Obtained from Aloe ferox by Spray Drying. 36832926 5 32 theme A. 890:891 arg1 ferox 893:897 A. ferox 890:897 A. ferox 890:897 Further, FP, such as swelling, increased around 25% when A. ferox was spray-dried at 160 °C, while water retention and fat adsorption capacities exhibited lower values when the drying temperature increased. 36832926 3 33 theme >90 517:519 arg1 % 520:520 % 520:520 % 520:520 Further, an acetylated mannan with a degree of acetylation >90% was detected in A. ferox by 1H NMR and FTIR. 36832926 5 34 theme drying 1010:1015 arg1 temperature 1017:1027 the drying temperature 1006:1027 the drying temperature 1006:1027 Further, FP, such as swelling, increased around 25% when A. ferox was spray-dried at 160 °C, while water retention and fat adsorption capacities exhibited lower values when the drying temperature increased. 36832926 2 35 theme A. 314:315 arg1 polysaccharides 323:337 A. ferox polysaccharides 314:337 A. ferox polysaccharides 314:337 A. ferox polysaccharides were comprised mainly of mannose, accounting for >70% of SD aloe mucilages; similar results were observed for A. vera. 36832926 5 36 dep such 846:849 arg1 as 851:852 as 851:852 as 851:852 Further, FP, such as swelling, increased around 25% when A. ferox was spray-dried at 160 °C, while water retention and fat adsorption capacities exhibited lower values when the drying temperature increased. 36832926 6 37 dep together 1114:1121 arg1 with 1123:1126 with 1123:1126 with 1123:1126 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 3 38 theme % 520:520 arg1 degree 495:500 a degree 493:500 a degree of acetylation >90% 493:520 Further, an acetylated mannan with a degree of acetylation >90% was detected in A. ferox by 1H NMR and FTIR. 36832926 4 39 theme antioxidant 752:762 arg1 consequence 814:824 a consequence 812:824 a consequence of SD 812:830 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 4 39 theme antioxidant 752:762 arg1 capacity 764:771 the antioxidant capacity 748:771 the antioxidant capacity measured by ABTS 748:788 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 1 40 theme total 213:217 arg1 TPC 239:241 TPC 239:241 TPC 239:241 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 1 40 theme total 213:217 arg1 compounds 228:236 total phenolic compounds 213:236 total phenolic compounds (TPC) 213:242 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 2 41 theme similar 415:421 arg1 results 423:429 similar results 415:429 similar results 415:429 A. ferox polysaccharides were comprised mainly of mannose, accounting for >70% of SD aloe mucilages; similar results were observed for A. vera. 36832926 3 42 located detected 526:533 arg1 ferox 541:545 A. ferox 538:545 A. ferox 538:545 Further, an acetylated mannan with a degree of acetylation >90% was detected in A. ferox by 1H NMR and FTIR. 36832926 3 42 located detected 526:533 arg2 mannan 481:486 an acetylated mannan 467:486 an acetylated mannan with a degree of acetylation >90% 467:520 Further, an acetylated mannan with a degree of acetylation >90% was detected in A. ferox by 1H NMR and FTIR. 36832926 0 43 theme Aloe 47:50 arg1 ferox 52:56 Aloe ferox 47:56 Aloe ferox 47:56 A New Functional Food Ingredient Obtained from Aloe ferox by Spray Drying. 36832926 1 44 theme phenolic 219:226 arg1 TPC 239:241 TPC 239:241 TPC 239:241 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 1 44 theme phenolic 219:226 arg1 compounds 228:236 total phenolic compounds 213:236 total phenolic compounds (TPC) 213:242 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 3 45 theme acetylation 505:515 arg1 degree 495:500 a degree 493:500 a degree of acetylation >90% 493:520 Further, an acetylated mannan with a degree of acetylation >90% was detected in A. ferox by 1H NMR and FTIR. 36832926 4 46 theme ABTS 653:656 arg1 methods 667:673 both ABTS and DPPH methods 648:673 methods 667:673 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 1 47 theme Aloe 93:96 arg1 ferox 98:102 Aloe ferox 93:102 Aloe ferox (A. ferox) 93:113 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 1 47 theme Aloe 93:96 arg1 ferox 108:112 A. ferox 105:112 A. ferox 105:112 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 6 48 theme acetylation 1101:1111 arg1 degree 1091:1096 a high degree 1084:1096 a high degree of acetylation 1084:1111 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 49 theme ingredients 1277:1287 arg1 development 1242:1252 the development 1238:1252 the development of new functional food ingredients based on Aloe plants 1238:1308 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 1 50 theme ferox 98:102 arg1 mucilages 80:88 Aloe mucilages 75:88 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) 75:137 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 2 51 theme A. 449:450 arg1 vera 452:455 A. vera 449:455 A. vera 449:455 A. ferox polysaccharides were comprised mainly of mannose, accounting for >70% of SD aloe mucilages; similar results were observed for A. vera. 36832926 3 52 theme A. 538:539 arg1 ferox 541:545 A. ferox 538:545 A. ferox 538:545 Further, an acetylated mannan with a degree of acetylation >90% was detected in A. ferox by 1H NMR and FTIR. 36832926 1 53 dep spray-dried 144:154 arg1 SD 157:158 SD 157:158 SD 157:158 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 3 54 theme acetylated 470:479 arg1 mannan 481:486 an acetylated mannan 467:486 an acetylated mannan with a degree of acetylation >90% 467:520 Further, an acetylated mannan with a degree of acetylation >90% was detected in A. ferox by 1H NMR and FTIR. 36832926 6 55 theme food 1272:1275 arg1 ingredients 1277:1287 new functional food ingredients 1257:1287 new functional food ingredients based on Aloe plants 1257:1308 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 56 theme functional 1261:1270 arg1 ingredients 1277:1287 new functional food ingredients 1257:1287 new functional food ingredients based on Aloe plants 1257:1308 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 1 57 theme A. 105:106 arg1 ferox 98:102 Aloe ferox 93:102 Aloe ferox (A. ferox) 93:113 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 1 57 theme A. 105:106 arg1 ferox 108:112 A. ferox 105:112 A. ferox 105:112 Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. 36832926 4 58 theme SD 829:830 arg1 consequence 814:824 a consequence 812:824 a consequence of SD 812:830 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 4 58 theme SD 829:830 arg1 capacity 764:771 the antioxidant capacity 748:771 the antioxidant capacity measured by ABTS 748:788 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 3 59 with mannan 481:486 arg1 degree 495:500 a degree 493:500 a degree of acetylation >90% 493:520 Further, an acetylated mannan with a degree of acetylation >90% was detected in A. ferox by 1H NMR and FTIR. 36832926 4 60 theme ferox 630:634 arg1 capacity 615:622 the antioxidant capacity 599:622 the antioxidant capacity of A. ferox 599:634 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 6 61 theme new 1257:1259 arg1 ingredients 1277:1287 new functional food ingredients 1257:1287 new functional food ingredients based on Aloe plants 1257:1308 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 62 theme A. 1180:1181 arg1 material 1225:1232 a valuable alternative raw material 1198:1232 a valuable alternative raw material 1198:1232 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 62 theme A. 1180:1181 arg1 ferox 1183:1187 SD A. ferox 1177:1187 SD A. ferox 1177:1187 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 63 theme SD 1177:1178 arg1 material 1225:1232 a valuable alternative raw material 1198:1232 a valuable alternative raw material 1198:1232 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 63 theme SD 1177:1178 arg1 ferox 1183:1187 SD A. ferox 1177:1187 SD A. ferox 1177:1187 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 4 64 theme A. 739:740 arg1 vera 742:745 A. vera 739:745 A. vera 739:745 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 3 65 theme 1H 550:551 arg1 NMR 553:555 1H NMR 550:555 1H NMR 550:555 Further, an acetylated mannan with a degree of acetylation >90% was detected in A. ferox by 1H NMR and FTIR. 36832926 4 66 theme A. 627:628 arg1 ferox 630:634 A. ferox 627:634 A. ferox 627:634 SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. 36832926 6 67 with mannan 1072:1077 arg1 degree 1091:1096 a high degree 1084:1096 a high degree of acetylation 1084:1111 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 6 68 theme antioxidant 1141:1151 arg1 capacity 1153:1160 the enhanced antioxidant capacity 1128:1160 the enhanced antioxidant capacity 1128:1160 The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants. 36832926 5 69 theme water 932:936 arg1 retention 938:946 water retention 932:946 water retention 932:946 Further, FP, such as swelling, increased around 25% when A. ferox was spray-dried at 160 °C, while water retention and fat adsorption capacities exhibited lower values when the drying temperature increased. 36143716 5 0 dep spectroscopy 810:821 arg1 wherein 823:829 wherein 823:829 wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation 823:975 Their structure was analyzed via FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation. 36143716 5 1 theme regular 891:897 arg1 measurements 918:929 regular pH and temperature measurements 891:929 regular pH and temperature measurements of these liquids 891:946 Their structure was analyzed via FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation. 36143716 9 2 theme crosslinker 1646:1656 arg1 amount 1632:1637 the amount 1628:1637 the amount of the crosslinker 1628:1656 Next, it was proved that as the amount of the crosslinker increased, hydrogels' crosslinking density increased and thus their swelling ratio decreased. 36143716 9 2 theme crosslinker 1646:1656 arg1 crosslinker 1646:1656 the crosslinker 1642:1656 the crosslinker 1642:1656 Next, it was proved that as the amount of the crosslinker increased, hydrogels' crosslinking density increased and thus their swelling ratio decreased. 36143716 3 3 contain containing 514:523 arg2 acid 556:559 L-ascorbic acid 545:559 L-ascorbic acid 545:559 In this work, PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid were obtained via UV-induced polymerization. 36143716 3 3 contain containing 514:523 arg1 hydrogels 504:512 PVP-based hydrogels 494:512 PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid 494:559 In this work, PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid were obtained via UV-induced polymerization. 36143716 3 3 contain containing 514:523 arg2 juice 535:539 Aloe vera juice 525:539 Aloe vera juice 525:539 In this work, PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid were obtained via UV-induced polymerization. 36143716 3 4 theme PVP-based 494:502 arg1 hydrogels 504:512 PVP-based hydrogels 494:512 PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid 494:559 In this work, PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid were obtained via UV-induced polymerization. 36143716 8 5 theme additive 1590:1597 arg1 composition 1570:1580 the composition 1566:1580 the composition of this additive 1566:1597 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 9 6 theme swelling 1726:1733 arg1 ratio 1735:1739 thus their swelling ratio 1715:1739 thus their swelling ratio 1715:1739 Next, it was proved that as the amount of the crosslinker increased, hydrogels' crosslinking density increased and thus their swelling ratio decreased. 36143716 8 7 theme media 1469:1473 arg1 pH 1448:1449 the pH 1444:1449 the pH of the incubation media 1444:1473 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 11 8 theme crosslinking 1983:1994 arg1 agent 1996:2000 the crosslinking agent 1979:2000 the crosslinking agent 1979:2000 Moreover, as the amount of the crosslinking agent increased, the tensile strength of hydrogels as well as their percentage elongation also increased. 36143716 10 9 theme average 1926:1932 arg1 weight 1944:1949 lower average molecular weight 1920:1949 lower average molecular weight 1920:1949 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 2 10 theme materials 280:288 arg1 wherein 362:368 materials showing the most advantageous properties from the application viewpoint wherein 280:368 materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties 280:477 It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. 36143716 2 11 dep wherein 362:368 arg1 affect 455:460 affect 455:460 affect their properties 455:477 It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. 36143716 5 12 theme simulated 851:859 arg1 liquids 866:872 the simulated body liquids 847:872 the simulated body liquids 847:872 Their structure was analyzed via FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation. 36143716 0 13 theme Foot 124:127 arg1 Ulcers 129:134 Diabetic Foot Ulcers 115:134 Diabetic Foot Ulcers 115:134 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials Designed as Dressings for Diabetic Foot Ulcers. 36143716 10 14 theme lower 1920:1924 arg1 weight 1944:1949 lower average molecular weight 1920:1949 lower average molecular weight 1920:1949 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 10 15 with crosslinker 1903:1913 arg1 weight 1944:1949 lower average molecular weight 1920:1949 lower average molecular weight 1920:1949 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 3 16 theme Aloe 525:528 arg1 juice 535:539 Aloe vera juice 525:539 Aloe vera juice 525:539 In this work, PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid were obtained via UV-induced polymerization. 36143716 1 17 theme polymers 170:177 arg1 polymers 170:177 polymers 170:177 polymers that are more and more often considered as innovative dressing materials 170:250 Hydrogels belong to the group of polymers that are more and more often considered as innovative dressing materials. 36143716 1 17 theme polymers 170:177 arg1 materials 242:250 innovative dressing materials 222:250 innovative dressing materials 222:250 Hydrogels belong to the group of polymers that are more and more often considered as innovative dressing materials. 36143716 1 17 theme polymers 170:177 arg1 group 161:165 the group 157:165 the group of polymers that are more and more often considered as innovative dressing materials 157:250 Hydrogels belong to the group of polymers that are more and more often considered as innovative dressing materials. 36143716 0 18 theme Diabetic 115:122 arg1 Ulcers 129:134 Diabetic Foot Ulcers 115:134 Diabetic Foot Ulcers 115:134 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials Designed as Dressings for Diabetic Foot Ulcers. 36143716 0 19 theme Physicochemical 0:14 arg1 Evaluation 16:25 Physicochemical Evaluation 0:25 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials 0:87 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials Designed as Dressings for Diabetic Foot Ulcers. 36143716 11 20 theme tensile 2017:2023 arg1 strength 2025:2032 the tensile strength 2013:2032 the tensile strength of hydrogels as well as their percentage elongation 2013:2084 Moreover, as the amount of the crosslinking agent increased, the tensile strength of hydrogels as well as their percentage elongation also increased. 36143716 4 21 theme optical 647:653 arg1 microscope 686:695 both optical, digital and scanning electron microscope 642:695 microscope 686:695 Next, their surface morphology (via both optical, digital and scanning electron microscope), sorption capacity, tensile strength, and elongation were characterized. 36143716 2 22 theme agent 440:444 arg1 agent 440:444 the crosslinking agent 423:444 the crosslinking agent 423:444 It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. 36143716 2 22 theme agent 440:444 arg1 type 400:403 the type 396:403 the type 396:403 It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. 36143716 2 22 theme agent 440:444 arg1 amount 413:418 the amount 409:418 the amount of the crosslinking agent 409:444 It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. 36143716 10 23 theme molecular 1934:1942 arg1 weight 1944:1949 lower average molecular weight 1920:1949 lower average molecular weight 1920:1949 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 8 24 from decrease 1432:1439 arg1 pH 1448:1449 the pH 1444:1449 the pH of the incubation media 1444:1473 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 2 25 theme hydrogels 385:393 arg1 case 377:380 the case 373:380 the case of hydrogels 373:393 It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. 36143716 2 26 theme crosslinking 427:438 arg1 agent 440:444 the crosslinking agent 423:444 the crosslinking agent 423:444 It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. 36143716 8 27 theme band 1515:1518 arg1 disappearance 1483:1495 the disappearance 1479:1495 the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive 1479:1597 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 8 27 theme band 1515:1518 arg1 decrease 1432:1439 the decrease 1428:1439 the decrease in the pH of the incubation media 1428:1473 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 10 28 theme crosslinking 1779:1790 arg1 agent 1792:1796 a crosslinking agent 1777:1796 a crosslinking agent with higher average molecular weight 1777:1833 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 11 29 theme agent 1996:2000 arg1 agent 1996:2000 the crosslinking agent 1979:2000 the crosslinking agent 1979:2000 Moreover, as the amount of the crosslinking agent increased, the tensile strength of hydrogels as well as their percentage elongation also increased. 36143716 11 29 theme agent 1996:2000 arg1 amount 1969:1974 the amount 1965:1974 the amount of the crosslinking agent 1965:2000 Moreover, as the amount of the crosslinking agent increased, the tensile strength of hydrogels as well as their percentage elongation also increased. 36143716 2 30 theme advantageous 307:318 arg1 properties 320:329 the most advantageous properties 298:329 the most advantageous properties 298:329 It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. 36143716 4 31 theme digital 656:662 arg1 microscope 686:695 both optical, digital and scanning electron microscope 642:695 microscope 686:695 Next, their surface morphology (via both optical, digital and scanning electron microscope), sorption capacity, tensile strength, and elongation were characterized. 36143716 0 32 theme L-Ascorbic 30:39 arg1 Acid 41:44 L-Ascorbic Acid 30:44 L-Ascorbic Acid 30:44 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials Designed as Dressings for Diabetic Foot Ulcers. 36143716 5 33 theme FT-IR 804:808 arg1 spectroscopy 810:821 FT-IR spectroscopy 804:821 FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation 804:975 Their structure was analyzed via FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation. 36143716 11 34 theme hydrogels 2037:2045 arg1 strength 2025:2032 the tensile strength 2013:2032 the tensile strength of hydrogels as well as their percentage elongation 2013:2084 Moreover, as the amount of the crosslinking agent increased, the tensile strength of hydrogels as well as their percentage elongation also increased. 36143716 11 34 theme hydrogels 2037:2045 arg1 elongation 2075:2084 their percentage elongation 2058:2084 the tensile strength of hydrogels as well as their percentage elongation 2013:2084 Moreover, as the amount of the crosslinking agent increased, the tensile strength of hydrogels as well as their percentage elongation also increased. 36143716 8 35 theme vera 1381:1384 arg1 juice 1386:1390 Aloe vera juice 1376:1390 Aloe vera juice 1376:1390 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 2 36 theme most 302:305 arg1 properties 320:329 the most advantageous properties 298:329 the most advantageous properties 298:329 It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. 36143716 4 37 theme tensile 718:724 arg1 strength 726:733 tensile strength 718:733 tensile strength 718:733 Next, their surface morphology (via both optical, digital and scanning electron microscope), sorption capacity, tensile strength, and elongation were characterized. 36143716 5 38 theme liquids 940:946 arg1 measurements 918:929 regular pH and temperature measurements 891:929 regular pH and temperature measurements of these liquids 891:946 Their structure was analyzed via FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation. 36143716 5 39 theme pH 899:900 arg1 measurements 918:929 regular pH and temperature measurements 891:929 regular pH and temperature measurements of these liquids 891:946 Their structure was analyzed via FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation. 36143716 8 40 dep wherein 1331:1337 arg1 took 1401:1404 took 1401:1404 probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive 1392:1597 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 5 41 theme temperature 906:916 arg1 measurements 918:929 regular pH and temperature measurements 891:929 regular pH and temperature measurements of these liquids 891:946 Their structure was analyzed via FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation. 36143716 8 42 theme Aloe 1376:1379 arg1 juice 1386:1390 Aloe vera juice 1376:1390 Aloe vera juice 1376:1390 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 6 43 theme polymer 1051:1057 arg1 structure 1059:1067 the polymer structure 1047:1067 the polymer structure 1047:1067 It was demonstrated that as the amount of the crosslinker increased, the polymer structure was more wrinkled. 36143716 6 43 theme polymer 1051:1057 arg1 wrinkled 1078:1085 wrinkled 1078:1085 wrinkled 1078:1085 It was demonstrated that as the amount of the crosslinker increased, the polymer structure was more wrinkled. 36143716 0 44 theme Acid 41:44 arg1 Evaluation 16:25 Physicochemical Evaluation 0:25 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials 0:87 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials Designed as Dressings for Diabetic Foot Ulcers. 36143716 10 45 theme average 1810:1816 arg1 weight 1828:1833 higher average molecular weight 1803:1833 higher average molecular weight 1803:1833 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 7 46 theme rough 1147:1151 arg1 surface 1153:1159 only slightly rough surface 1133:1159 only slightly rough surface 1133:1159 Next, hydrogels showed relatively smooth and only slightly rough surface, which was probably due to the fact that the modifiers filled also the outer pores of the materials. 36143716 10 47 theme molecular 1818:1826 arg1 weight 1828:1833 higher average molecular weight 1803:1833 higher average molecular weight 1803:1833 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 4 48 theme surface 618:624 arg1 morphology 626:635 their surface morphology 612:635 their surface morphology (via both optical, digital and scanning electron microscope) 612:696 Next, their surface morphology (via both optical, digital and scanning electron microscope), sorption capacity, tensile strength, and elongation were characterized. 36143716 6 49 theme crosslinker 1024:1034 arg1 amount 1010:1015 the amount 1006:1015 the amount of the crosslinker 1006:1034 It was demonstrated that as the amount of the crosslinker increased, the polymer structure was more wrinkled. 36143716 6 49 theme crosslinker 1024:1034 arg1 crosslinker 1024:1034 the crosslinker 1020:1034 the crosslinker 1020:1034 It was demonstrated that as the amount of the crosslinker increased, the polymer structure was more wrinkled. 36143716 0 50 theme vera-Containing 55:69 arg1 Materials 79:87 Aloe vera-Containing Polymer Materials 50:87 Aloe vera-Containing Polymer Materials 50:87 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials Designed as Dressings for Diabetic Foot Ulcers. 36143716 10 51 with agent 1792:1796 arg1 weight 1828:1833 higher average molecular weight 1803:1833 higher average molecular weight 1803:1833 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 8 52 theme absorption 1504:1513 arg1 band 1515:1518 the absorption band 1500:1518 the absorption band deriving from the polysaccharides included in the composition of this additive 1500:1597 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 8 53 theme juice 1386:1390 arg1 release 1365:1371 the release 1361:1371 the release of Aloe vera juice 1361:1390 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 4 54 theme sorption 699:706 arg1 capacity 708:715 sorption capacity 699:715 sorption capacity 699:715 Next, their surface morphology (via both optical, digital and scanning electron microscope), sorption capacity, tensile strength, and elongation were characterized. 36143716 0 55 theme Aloe 50:53 arg1 Materials 79:87 Aloe vera-Containing Polymer Materials 50:87 Aloe vera-Containing Polymer Materials 50:87 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials Designed as Dressings for Diabetic Foot Ulcers. 36143716 8 56 from disappearance 1483:1495 arg1 pH 1448:1449 the pH 1444:1449 the pH of the incubation media 1444:1473 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 11 57 theme percentage 2064:2073 arg1 elongation 2075:2084 their percentage elongation 2058:2084 the tensile strength of hydrogels as well as their percentage elongation 2013:2084 Moreover, as the amount of the crosslinking agent increased, the tensile strength of hydrogels as well as their percentage elongation also increased. 36143716 3 58 theme UV-induced 579:588 arg1 polymerization 590:603 UV-induced polymerization 579:603 UV-induced polymerization 579:603 In this work, PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid were obtained via UV-induced polymerization. 36143716 8 59 attach deriving 1520:1527 arg1 polysaccharides 1538:1552 the polysaccharides 1534:1552 the polysaccharides included in the composition of this additive 1534:1597 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 8 59 attach deriving 1520:1527 arg2 band 1515:1518 the absorption band 1500:1518 the absorption band deriving from the polysaccharides included in the composition of this additive 1500:1597 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 2 60 theme application 340:350 arg1 viewpoint 352:360 the application viewpoint 336:360 the application viewpoint 336:360 It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. 36143716 8 61 from properties 1295:1304 arg1 media 1324:1328 all incubation media 1309:1328 all incubation media 1309:1328 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 9 62 theme crosslinking 1680:1691 arg1 density 1693:1699 hydrogels' crosslinking density 1669:1699 hydrogels' crosslinking density 1669:1699 Next, it was proved that as the amount of the crosslinker increased, hydrogels' crosslinking density increased and thus their swelling ratio decreased. 36143716 10 63 theme higher 1803:1808 arg1 weight 1828:1833 higher average molecular weight 1803:1833 higher average molecular weight 1803:1833 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 5 64 from impact 837:842 arg1 liquids 866:872 the simulated body liquids 847:872 the simulated body liquids 847:872 Their structure was analyzed via FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation. 36143716 8 65 theme buffering 1285:1293 arg1 wherein 1331:1337 wherein 1331:1337 wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive 1331:1597 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 8 65 theme buffering 1285:1293 arg1 properties 1295:1304 buffering properties 1285:1304 buffering properties in all incubation media 1285:1328 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 3 66 theme L-ascorbic 545:554 arg1 acid 556:559 L-ascorbic acid 545:559 L-ascorbic acid 545:559 In this work, PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid were obtained via UV-induced polymerization. 36143716 3 67 theme vera 530:533 arg1 juice 535:539 Aloe vera juice 525:539 Aloe vera juice 525:539 In this work, PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid were obtained via UV-induced polymerization. 36143716 10 68 theme swelling 1849:1856 arg1 ability 1858:1864 higher swelling ability 1842:1864 higher swelling ability 1842:1864 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 7 69 theme outer 1232:1236 arg1 pores 1238:1242 the outer pores 1228:1242 the outer pores of the materials 1228:1259 Next, hydrogels showed relatively smooth and only slightly rough surface, which was probably due to the fact that the modifiers filled also the outer pores of the materials. 36143716 8 70 theme incubation 1313:1322 arg1 media 1324:1328 all incubation media 1309:1328 all incubation media 1309:1328 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 1 71 theme innovative 222:231 arg1 polymers 170:177 polymers 170:177 polymers that are more and more often considered as innovative dressing materials 170:250 Hydrogels belong to the group of polymers that are more and more often considered as innovative dressing materials. 36143716 1 71 theme innovative 222:231 arg1 materials 242:250 innovative dressing materials 222:250 innovative dressing materials 222:250 Hydrogels belong to the group of polymers that are more and more often considered as innovative dressing materials. 36143716 0 72 theme Materials 79:87 arg1 Evaluation 16:25 Physicochemical Evaluation 0:25 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials 0:87 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials Designed as Dressings for Diabetic Foot Ulcers. 36143716 10 73 theme higher 1842:1847 arg1 ability 1858:1864 higher swelling ability 1842:1864 higher swelling ability 1842:1864 Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. 36143716 4 74 theme electron 677:684 arg1 microscope 686:695 both optical, digital and scanning electron microscope 642:695 microscope 686:695 Next, their surface morphology (via both optical, digital and scanning electron microscope), sorption capacity, tensile strength, and elongation were characterized. 36143716 5 75 theme body 861:864 arg1 liquids 866:872 the simulated body liquids 847:872 the simulated body liquids 847:872 Their structure was analyzed via FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation. 36143716 1 76 theme dressing 233:240 arg1 polymers 170:177 polymers 170:177 polymers that are more and more often considered as innovative dressing materials 170:250 Hydrogels belong to the group of polymers that are more and more often considered as innovative dressing materials. 36143716 1 76 theme dressing 233:240 arg1 materials 242:250 innovative dressing materials 222:250 innovative dressing materials 222:250 Hydrogels belong to the group of polymers that are more and more often considered as innovative dressing materials. 36143716 0 77 theme Polymer 71:77 arg1 Materials 79:87 Aloe vera-Containing Polymer Materials 50:87 Aloe vera-Containing Polymer Materials 50:87 Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials Designed as Dressings for Diabetic Foot Ulcers. 36143716 8 78 theme incubation 1458:1467 arg1 media 1469:1473 the incubation media 1454:1473 the incubation media 1454:1473 Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. 36143716 7 79 theme materials 1251:1259 arg1 pores 1238:1242 the outer pores 1228:1242 the outer pores of the materials 1228:1259 Next, hydrogels showed relatively smooth and only slightly rough surface, which was probably due to the fact that the modifiers filled also the outer pores of the materials. 36143716 4 80 theme scanning 668:675 arg1 microscope 686:695 both optical, digital and scanning electron microscope 642:695 microscope 686:695 Next, their surface morphology (via both optical, digital and scanning electron microscope), sorption capacity, tensile strength, and elongation were characterized. 36617721 10 0 theme inconsistent 2360:2371 arg1 results 2380:2386 inconsistent marker results 2360:2386 inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract 2360:2474 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 3 1 theme biosynthetic 672:683 arg1 formation 685:693 The biosynthetic formation 668:693 The biosynthetic formation of the CW 668:703 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 1 2 theme primary 225:231 arg1 source 240:245 their primary energy source 219:245 their primary energy source 219:245 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 9 3 theme Different 2134:2142 arg1 variations 2144:2153 Different variations 2134:2153 Different variations of multicompartmental and time- and age-dependent mathematical models 2134:2223 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 2 4 theme due 583:585 arg1 matter 576:581 particulate matter 564:581 particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen 564:665 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 3 5 theme ruminant 993:1000 arg1 animal 1002:1007 the ruminant animal 989:1007 the ruminant animal 989:1007 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 6 theme possible 714:721 arg1 mechanisms 736:745 possible manipulation mechanisms 714:745 possible manipulation mechanisms (targeted plant and microbes selection) 714:785 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 6 theme possible 714:721 arg1 plant 757:761 targeted plant 748:761 targeted plant 748:761 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 6 theme possible 714:721 arg1 selection 776:784 microbes selection 767:784 microbes selection 767:784 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 5 7 theme modern 1436:1441 arg1 mechanisms 1456:1465 modern manipulation mechanisms 1436:1465 modern manipulation mechanisms 1436:1465 Concurrently, laboratory methods must be developed, evaluated, and modified to accurately and reliably reflect the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods. 36617721 4 8 theme lignin 1103:1108 arg1 biosynthesis 1110:1121 lignin biosynthesis 1103:1121 lignin biosynthesis 1103:1121 Early studies on lignin biosynthesis have led to more advanced studies focusing on replacing traditional monolignols with homopolymers that are easier to deconstruct or degrade. 36617721 3 9 theme CW 702:703 arg1 formation 685:693 The biosynthetic formation 668:693 The biosynthetic formation of the CW 668:703 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 1 10 theme polysaccharide 164:177 arg1 matrix 179:184 the complex polysaccharide matrix 152:184 the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source 152:245 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 2 11 dep characteristics 603:617 arg1 characteristics 603:617 its physical characteristics 590:617 its physical characteristics (buoyancy and comminuting) in the reticulorumen 590:665 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 11 dep characteristics 603:617 arg1 comminuting 633:643 comminuting 633:643 comminuting 633:643 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 11 dep characteristics 603:617 arg1 buoyancy 620:627 buoyancy 620:627 buoyancy 620:627 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 3 12 theme lower 1023:1027 arg1 contribution 1033:1044 the contribution 1029:1044 hopefully lower the contribution of ruminants' greenhouse gas emissions 1013:1083 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 13 theme targeted 748:755 arg1 mechanisms 736:745 possible manipulation mechanisms 714:745 possible manipulation mechanisms (targeted plant and microbes selection) 714:785 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 13 theme targeted 748:755 arg1 plant 757:761 targeted plant 748:761 targeted plant 748:761 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 5 14 theme CW 1416:1417 arg1 value 1407:1411 the digestibility and nutritive value 1375:1411 the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods 1375:1487 Concurrently, laboratory methods must be developed, evaluated, and modified to accurately and reliably reflect the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods. 36617721 10 15 theme incomplete 2337:2346 arg1 data 2348:2351 low-quality and incomplete data 2321:2351 low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract 2321:2474 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 10 16 theme next 2524:2527 arg1 generation 2529:2538 the next generation 2520:2538 the next generation of computer models 2520:2557 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 4 17 from studies 1092:1098 arg1 biosynthesis 1110:1121 lignin biosynthesis 1103:1121 lignin biosynthesis 1103:1121 Early studies on lignin biosynthesis have led to more advanced studies focusing on replacing traditional monolignols with homopolymers that are easier to deconstruct or degrade. 36617721 2 18 theme fiber 521:525 arg1 digestion 527:535 fiber digestion 521:535 fiber digestion 521:535 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 9 19 theme passage 2294:2300 arg1 rates 2269:2273 the ruminal rates 2257:2273 the ruminal rates of degradation and passage of fiber 2257:2309 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 9 20 theme models 2218:2223 arg1 variations 2144:2153 Different variations 2134:2153 Different variations of multicompartmental and time- and age-dependent mathematical models 2134:2223 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 2 21 theme particulate 564:574 arg1 matter 576:581 particulate matter 564:581 particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen 564:665 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 10 22 theme models 2552:2557 arg1 generation 2529:2538 the next generation 2520:2538 the next generation of computer models 2520:2557 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 9 23 theme mathematical 2205:2216 arg1 models 2218:2223 multicompartmental and time- and age-dependent mathematical models 2158:2223 multicompartmental and time- and age-dependent mathematical models 2158:2223 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 1 24 theme ruminant 108:115 arg1 animals 117:123 Several ruminant animals 100:123 Several ruminant animals 100:123 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 5 25 theme laboratory 1278:1287 arg1 methods 1289:1295 laboratory methods 1278:1295 laboratory methods 1278:1295 Concurrently, laboratory methods must be developed, evaluated, and modified to accurately and reliably reflect the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods. 36617721 7 26 theme detergent 1701:1709 arg1 lignin 1711:1716 the acid detergent lignin 1692:1716 the acid detergent lignin 1692:1716 For instance, although the acid detergent lignin has been demonstrated to behave uniformly as a nutritional entity, its chemical determination and association with carbohydrates still lack consensus. 36617721 10 27 theme fiber 2581:2585 arg1 degradation 2587:2597 ruminal fiber degradation 2573:2597 ruminal fiber degradation 2573:2597 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 3 28 dep mechanisms 736:745 arg1 mechanisms 736:745 possible manipulation mechanisms 714:745 possible manipulation mechanisms (targeted plant and microbes selection) 714:785 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 28 dep mechanisms 736:745 arg1 plant 757:761 targeted plant 748:761 targeted plant 748:761 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 28 dep mechanisms 736:745 arg1 selection 776:784 microbes selection 767:784 microbes selection 767:784 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 28 dep mechanisms 736:745 arg1 treatments 856:865 physical, chemical, microbial, and enzymatic treatments 811:865 physical, chemical, microbial, and enzymatic treatments 811:865 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 28 dep mechanisms 736:745 arg1 use 875:877 the use 871:877 the use of genetically engineered bacteria 871:912 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 4 29 theme advanced 1140:1147 arg1 studies 1149:1155 more advanced studies 1135:1155 more advanced studies focusing on replacing traditional monolignols with homopolymers that are easier to deconstruct or degrade 1135:1261 Early studies on lignin biosynthesis have led to more advanced studies focusing on replacing traditional monolignols with homopolymers that are easier to deconstruct or degrade. 36617721 3 30 theme chemical 821:828 arg1 treatments 856:865 physical, chemical, microbial, and enzymatic treatments 811:865 physical, chemical, microbial, and enzymatic treatments 811:865 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 0 31 theme Cell 63:66 arg1 Utilization 73:83 Cell Wall Utilization 63:83 Cell Wall Utilization for Ruminants 63:97 Revisiting Mechanisms, Methods, and Models for Altering Forage Cell Wall Utilization for Ruminants. 36617721 1 32 theme fermentation 314:325 arg1 processes 327:335 some hindgut fermentation processes 301:335 some hindgut fermentation processes 301:335 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 6 33 theme same 1623:1626 arg1 time 1628:1631 the same time 1619:1631 the same time 1619:1631 However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. 36617721 6 34 dep implement 1581:1589 arg1 to 1578:1579 to 1578:1579 to 1578:1579 However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. 36617721 2 35 from compounds 425:433 arg1 structure 473:481 their macromolecular structure 452:481 their macromolecular structure 452:481 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 3 36 theme physical 811:818 arg1 treatments 856:865 physical, chemical, microbial, and enzymatic treatments 811:865 physical, chemical, microbial, and enzymatic treatments 811:865 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 37 theme contribution 1033:1044 arg1 utilization 964:974 better utilization 957:974 better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions 957:1083 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 38 theme engineered 894:903 arg1 bacteria 905:912 genetically engineered bacteria 882:912 genetically engineered bacteria 882:912 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 10 39 theme passage 2406:2412 arg1 rates 2414:2418 passage rates 2406:2418 passage rates 2406:2418 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 3 40 theme microbial 831:839 arg1 treatments 856:865 physical, chemical, microbial, and enzymatic treatments 811:865 physical, chemical, microbial, and enzymatic treatments 811:865 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 8 41 theme chemical 1981:1988 arg1 composition 1990:2000 plant chemical composition 1975:2000 plant chemical composition 1975:2000 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 10 42 theme fiber 2440:2444 arg1 rates 2414:2418 passage rates 2406:2418 passage rates 2406:2418 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 10 42 theme fiber 2440:2444 arg1 time 2432:2435 transit time 2424:2435 transit time of fiber 2424:2444 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 5 43 theme processing 1470:1479 arg1 methods 1481:1487 processing methods 1470:1487 processing methods 1470:1487 Concurrently, laboratory methods must be developed, evaluated, and modified to accurately and reliably reflect the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods. 36617721 0 44 theme Revisiting 0:9 arg1 Mechanisms 11:20 Revisiting Mechanisms 0:20 Revisiting Mechanisms 0:20 Revisiting Mechanisms, Methods, and Models for Altering Forage Cell Wall Utilization for Ruminants. 36617721 3 45 theme greenhouse 1060:1069 arg1 emissions 1075:1083 greenhouse gas emissions 1060:1083 ruminants' greenhouse gas emissions 1049:1083 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 8 46 theme impacts 2062:2068 arg1 understanding 2041:2053 an incomplete understanding 2027:2053 an incomplete understanding of the impacts caused by disrupting the CW for sample processing 2027:2118 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 2 47 theme phenolic 416:423 arg1 compounds 425:433 phenolic compounds 416:433 phenolic compounds 416:433 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 48 theme proteins 406:413 arg1 proportions 374:384 proportions 374:384 proportions 374:384 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 48 theme proteins 406:413 arg1 types 364:368 different types 354:368 different types 354:368 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 3 49 dep ruminants 1049:1057 arg1 emissions 1075:1083 greenhouse gas emissions 1060:1083 ruminants' greenhouse gas emissions 1049:1083 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 1 50 theme fatty 260:264 arg1 acids 266:270 volatile fatty acids 251:270 volatile fatty acids produced through ruminal and some hindgut fermentation processes 251:335 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 8 51 dep in 1912:1913 arg1 vitro 1915:1919 vitro 1915:1919 vitro 1915:1919 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 2 52 theme polysaccharides 389:403 arg1 proportions 374:384 proportions 374:384 proportions 374:384 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 52 theme polysaccharides 389:403 arg1 types 364:368 different types 354:368 different types 354:368 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 53 from types 364:368 arg1 structure 473:481 their macromolecular structure 452:481 their macromolecular structure 452:481 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 54 theme minerals 440:447 arg1 proportions 374:384 proportions 374:384 proportions 374:384 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 54 theme minerals 440:447 arg1 types 364:368 different types 354:368 different types 354:368 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 5 55 theme digestibility 1379:1391 arg1 value 1407:1411 the digestibility and nutritive value 1375:1411 the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods 1375:1487 Concurrently, laboratory methods must be developed, evaluated, and modified to accurately and reliably reflect the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods. 36617721 8 56 theme incomplete 2030:2039 arg1 understanding 2041:2053 an incomplete understanding 2027:2053 an incomplete understanding of the impacts caused by disrupting the CW for sample processing 2027:2118 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 2 57 from proportions 374:384 arg1 structure 473:481 their macromolecular structure 452:481 their macromolecular structure 452:481 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 5 58 theme nutritive 1397:1405 arg1 value 1407:1411 the digestibility and nutritive value 1375:1411 the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods 1375:1487 Concurrently, laboratory methods must be developed, evaluated, and modified to accurately and reliably reflect the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods. 36617721 7 59 theme chemical 1789:1796 arg1 determination 1798:1810 its chemical determination 1785:1810 its chemical determination 1785:1810 For instance, although the acid detergent lignin has been demonstrated to behave uniformly as a nutritional entity, its chemical determination and association with carbohydrates still lack consensus. 36617721 3 60 theme better 957:962 arg1 utilization 964:974 better utilization 957:974 better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions 957:1083 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 7 61 with determination 1798:1810 arg1 carbohydrates 1833:1845 carbohydrates 1833:1845 carbohydrates 1833:1845 For instance, although the acid detergent lignin has been demonstrated to behave uniformly as a nutritional entity, its chemical determination and association with carbohydrates still lack consensus. 36617721 7 62 theme nutritional 1765:1775 arg1 entity 1777:1782 a nutritional entity 1763:1782 a nutritional entity 1763:1782 For instance, although the acid detergent lignin has been demonstrated to behave uniformly as a nutritional entity, its chemical determination and association with carbohydrates still lack consensus. 36617721 7 63 with association 1816:1826 arg1 carbohydrates 1833:1845 carbohydrates 1833:1845 carbohydrates 1833:1845 For instance, although the acid detergent lignin has been demonstrated to behave uniformly as a nutritional entity, its chemical determination and association with carbohydrates still lack consensus. 36617721 1 64 theme energy 233:238 arg1 source 240:245 their primary energy source 219:245 their primary energy source 219:245 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 2 65 theme matter 576:581 arg1 rate 502:505 rate 502:505 rate 502:505 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 65 theme matter 576:581 arg1 retention 551:559 selective retention 541:559 selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen 541:665 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 65 theme matter 576:581 arg1 extent 511:516 extent 511:516 extent 511:516 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 3 66 theme CW 983:984 arg1 utilization 964:974 better utilization 957:974 better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions 957:1083 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 67 theme manipulation 723:734 arg1 mechanisms 736:745 possible manipulation mechanisms 714:745 possible manipulation mechanisms (targeted plant and microbes selection) 714:785 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 67 theme manipulation 723:734 arg1 plant 757:761 targeted plant 748:761 targeted plant 748:761 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 67 theme manipulation 723:734 arg1 selection 776:784 microbes selection 767:784 microbes selection 767:784 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 5 68 theme manipulation 1443:1454 arg1 mechanisms 1456:1465 modern manipulation mechanisms 1436:1465 modern manipulation mechanisms 1436:1465 Concurrently, laboratory methods must be developed, evaluated, and modified to accurately and reliably reflect the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods. 36617721 1 69 theme complex 156:162 arg1 matrix 179:184 the complex polysaccharide matrix 152:184 the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source 152:245 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 10 70 theme marker 2373:2378 arg1 results 2380:2386 inconsistent marker results 2360:2386 inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract 2360:2474 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 6 71 dep reliable 1535:1542 arg1 friendly 1649:1656 friendly 1649:1656 friendly 1649:1656 However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. 36617721 6 71 dep reliable 1535:1542 arg1 reliable 1535:1542 reliable 1535:1542 reliable 1535:1542 However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. 36617721 6 71 dep reliable 1535:1542 arg1 methods 1514:1520 the laboratory methods 1499:1520 the laboratory methods 1499:1520 However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. 36617721 6 71 dep reliable 1535:1542 arg1 aware 1662:1666 aware 1662:1666 aware 1662:1666 However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. 36617721 8 72 dep Spectroscopy 1869:1880 arg1 Raman 1901:1905 Raman 1901:1905 Raman 1901:1905 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 8 72 dep Spectroscopy 1869:1880 arg1 near-infrared 1883:1895 near-infrared 1883:1895 near-infrared 1883:1895 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 8 72 dep Spectroscopy 1869:1880 arg1 techniques 1936:1945 techniques 1936:1945 techniques 1936:1945 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 2 73 theme physical 594:601 arg1 characteristics 603:617 its physical characteristics 590:617 its physical characteristics (buoyancy and comminuting) in the reticulorumen 590:665 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 73 theme physical 594:601 arg1 comminuting 633:643 comminuting 633:643 comminuting 633:643 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 73 theme physical 594:601 arg1 buoyancy 620:627 buoyancy 620:627 buoyancy 620:627 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 4 74 theme Early 1086:1090 arg1 studies 1092:1098 Early studies 1086:1098 Early studies on lignin biosynthesis 1086:1121 Early studies on lignin biosynthesis have led to more advanced studies focusing on replacing traditional monolignols with homopolymers that are easier to deconstruct or degrade. 36617721 9 75 theme multicompartmental 2158:2175 arg1 models 2218:2223 multicompartmental and time- and age-dependent mathematical models 2158:2223 multicompartmental and time- and age-dependent mathematical models 2158:2223 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 2 76 theme digestion 527:535 arg1 rate 502:505 rate 502:505 rate 502:505 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 76 theme digestion 527:535 arg1 retention 551:559 selective retention 541:559 selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen 541:665 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 76 theme digestion 527:535 arg1 extent 511:516 extent 511:516 extent 511:516 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 77 from structure 473:481 arg1 proportions 374:384 proportions 374:384 proportions 374:384 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 77 from structure 473:481 arg1 types 364:368 different types 354:368 different types 354:368 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 9 78 theme time- 2181:2185 arg1 models 2218:2223 multicompartmental and time- and age-dependent mathematical models 2158:2223 multicompartmental and time- and age-dependent mathematical models 2158:2223 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 8 79 theme in 1912:1913 arg1 production 1925:1934 in vitro gas production 1912:1934 in vitro gas production 1912:1934 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 6 80 theme laboratory 1503:1512 arg1 friendly 1649:1656 friendly 1649:1656 friendly 1649:1656 However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. 36617721 6 80 theme laboratory 1503:1512 arg1 reliable 1535:1542 reliable 1535:1542 reliable 1535:1542 However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. 36617721 6 80 theme laboratory 1503:1512 arg1 methods 1514:1520 the laboratory methods 1499:1520 the laboratory methods 1499:1520 However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. 36617721 6 80 theme laboratory 1503:1512 arg1 aware 1662:1666 aware 1662:1666 aware 1662:1666 However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. 36617721 1 81 theme cell 201:204 arg1 CW 212:213 CW 212:213 CW 212:213 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 1 81 theme cell 201:204 arg1 wall 206:209 the plant cell wall 191:209 the plant cell wall (CW) 191:214 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 9 82 theme age-dependent 2191:2203 arg1 models 2218:2223 multicompartmental and time- and age-dependent mathematical models 2158:2223 multicompartmental and time- and age-dependent mathematical models 2158:2223 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 8 83 theme gas 1921:1923 arg1 production 1925:1934 in vitro gas production 1912:1934 in vitro gas production 1912:1934 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 1 84 from wall 206:209 arg1 matrix 179:184 the complex polysaccharide matrix 152:184 the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source 152:245 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 1 85 theme Several 100:106 arg1 animals 117:123 Several ruminant animals 100:123 Several ruminant animals 100:123 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 4 86 theme traditional 1179:1189 arg1 monolignols 1191:1201 traditional monolignols 1179:1201 traditional monolignols 1179:1201 Early studies on lignin biosynthesis have led to more advanced studies focusing on replacing traditional monolignols with homopolymers that are easier to deconstruct or degrade. 36617721 10 87 theme computer 2543:2550 arg1 models 2552:2557 computer models 2543:2557 computer models 2543:2557 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 3 88 theme microbes 767:774 arg1 mechanisms 736:745 possible manipulation mechanisms 714:745 possible manipulation mechanisms (targeted plant and microbes selection) 714:785 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 88 theme microbes 767:774 arg1 selection 776:784 microbes selection 767:784 microbes selection 767:784 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 89 theme enzymatic 846:854 arg1 treatments 856:865 physical, chemical, microbial, and enzymatic treatments 811:865 physical, chemical, microbial, and enzymatic treatments 811:865 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 2 90 theme selective 541:549 arg1 retention 551:559 selective retention 541:559 selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen 541:665 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 10 91 theme generation 2529:2538 arg1 advancements 2490:2501 advancements 2490:2501 advancements 2490:2501 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 10 91 theme generation 2529:2538 arg1 adoptions 2507:2515 adoptions 2507:2515 adoptions 2507:2515 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 9 92 theme ruminal 2261:2267 arg1 rates 2269:2273 the ruminal rates 2257:2273 the ruminal rates of degradation and passage of fiber 2257:2309 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 10 93 theme ruminal 2573:2579 arg1 degradation 2587:2597 ruminal fiber degradation 2573:2597 ruminal fiber degradation 2573:2597 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 3 94 theme processing 791:800 arg1 methods 802:808 processing methods 791:808 processing methods 791:808 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 0 95 theme Wall 68:71 arg1 Utilization 73:83 Cell Wall Utilization 63:83 Cell Wall Utilization for Ruminants 63:97 Revisiting Mechanisms, Methods, and Models for Altering Forage Cell Wall Utilization for Ruminants. 36617721 1 96 theme hindgut 306:312 arg1 processes 327:335 some hindgut fermentation processes 301:335 some hindgut fermentation processes 301:335 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 7 97 theme acid 1696:1699 arg1 lignin 1711:1716 the acid detergent lignin 1692:1716 the acid detergent lignin 1692:1716 For instance, although the acid detergent lignin has been demonstrated to behave uniformly as a nutritional entity, its chemical determination and association with carbohydrates still lack consensus. 36617721 2 98 theme macromolecular 458:471 arg1 structure 473:481 their macromolecular structure 452:481 their macromolecular structure 452:481 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 8 99 theme plant 1975:1979 arg1 composition 1990:2000 plant chemical composition 1975:2000 plant chemical composition 1975:2000 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 2 100 from polysaccharides 389:403 arg1 structure 473:481 their macromolecular structure 452:481 their macromolecular structure 452:481 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 101 from minerals 440:447 arg1 structure 473:481 their macromolecular structure 452:481 their macromolecular structure 452:481 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 3 102 theme gas 1071:1073 arg1 emissions 1075:1083 greenhouse gas emissions 1060:1083 ruminants' greenhouse gas emissions 1049:1083 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 1 103 theme plant 195:199 arg1 CW 212:213 CW 212:213 CW 212:213 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 1 103 theme plant 195:199 arg1 wall 206:209 the plant cell wall 191:209 the plant cell wall (CW) 191:214 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 3 104 theme bacteria 905:912 arg1 treatments 856:865 physical, chemical, microbial, and enzymatic treatments 811:865 physical, chemical, microbial, and enzymatic treatments 811:865 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 3 104 theme bacteria 905:912 arg1 use 875:877 the use 871:877 the use of genetically engineered bacteria 871:912 The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants' greenhouse gas emissions. 36617721 9 105 theme degradation 2278:2288 arg1 rates 2269:2273 the ruminal rates 2257:2273 the ruminal rates of degradation and passage of fiber 2257:2309 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 8 106 theme nutritive 2006:2014 arg1 value 2016:2020 nutritive value 2006:2020 nutritive value 2006:2020 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 2 107 contain contains 345:352 arg2 proportions 374:384 proportions 374:384 proportions 374:384 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 107 contain contains 345:352 arg1 CW 342:343 The CW 338:343 The CW 338:343 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 107 contain contains 345:352 arg2 types 364:368 different types 354:368 different types 354:368 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 108 theme compounds 425:433 arg1 proportions 374:384 proportions 374:384 proportions 374:384 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 108 theme compounds 425:433 arg1 types 364:368 different types 354:368 different types 354:368 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 2 109 theme different 354:362 arg1 types 364:368 different types 354:368 different types 354:368 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 10 110 theme low-quality 2321:2331 arg1 data 2348:2351 low-quality and incomplete data 2321:2351 low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract 2321:2474 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 1 111 theme volatile 251:258 arg1 acids 266:270 volatile fatty acids 251:270 volatile fatty acids produced through ruminal and some hindgut fermentation processes 251:335 Several ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. 36617721 2 112 dep rate 502:505 arg1 the 498:500 the 498:500 the 498:500 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 10 113 theme transit 2424:2430 arg1 time 2432:2435 transit time 2424:2435 transit time of fiber 2424:2444 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 9 114 theme fiber 2305:2309 arg1 passage 2294:2300 passage 2294:2300 passage 2294:2300 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 9 114 theme fiber 2305:2309 arg1 degradation 2278:2288 degradation 2278:2288 degradation 2278:2288 Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. 36617721 10 115 theme gastrointestinal 2453:2468 arg1 tract 2470:2474 the gastrointestinal tract 2449:2474 the gastrointestinal tract 2449:2474 However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation. 36617721 2 116 from characteristics 603:617 arg1 reticulorumen 653:665 the reticulorumen 649:665 the reticulorumen 649:665 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 36617721 8 117 theme sample 2102:2107 arg1 processing 2109:2118 sample processing 2102:2118 sample processing 2102:2118 Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. 36617721 2 118 from proteins 406:413 arg1 structure 473:481 their macromolecular structure 452:481 their macromolecular structure 452:481 The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. 37097176 6 0 theme expression 1066:1075 arg1 levels 1077:1082 cellular expression levels 1057:1082 cellular expression levels of essential factors such as AAVR or GPR108 1057:1126 Recombinant furin does not cleave AAV4 capsid proteins nor alter cellular expression levels of essential factors such as AAVR or GPR108. 37097176 13 1 theme gene 2419:2422 arg1 expression 2424:2433 gene expression 2419:2433 gene expression 2419:2433 Based on the findings, we postulate that differential expression of furin in host cells and tissues is likely to influence gene expression by certain recombinant AAV serotypes. 37097176 4 2 theme transduction 587:598 arg1 efficiency 600:609 the transduction efficiency 583:609 the transduction efficiency of most recombinant AAV serotypes tested 583:650 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 12 3 theme intracellular 2179:2191 arg1 protease 2193:2200 a common intracellular protease 2170:2200 a common intracellular protease 2170:2200 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 10 4 theme vector 1919:1924 arg1 IMPORTANCE 1851:1860 IMPORTANCE Adeno-associated viruses (AAVs) 1851:1892 IMPORTANCE Adeno-associated viruses (AAVs) 1851:1892 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 10 4 theme vector 1919:1924 arg1 platform 1926:1933 a proven recombinant vector platform 1898:1933 a proven recombinant vector platform for gene therapy 1898:1950 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 7 5 from surface 1244:1250 arg1 increase 1191:1198 a marked increase 1182:1198 a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells 1182:1290 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 10 6 theme proven 1900:1905 arg1 IMPORTANCE 1851:1860 IMPORTANCE Adeno-associated viruses (AAVs) 1851:1892 IMPORTANCE Adeno-associated viruses (AAVs) 1851:1892 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 10 6 theme proven 1900:1905 arg1 platform 1926:1933 a proven recombinant vector platform 1898:1933 a proven recombinant vector platform for gene therapy 1898:1950 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 4 7 theme striking 667:674 arg1 increase 676:683 a striking increase 665:683 a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4 665:765 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 11 8 theme AAV-host 2036:2043 arg1 interactions 2050:2061 AAV-host cell interactions 2036:2061 AAV-host cell interactions 2036:2061 Continuing to improve our knowledge of AAV-host cell interactions is critical for improving the safety and efficacy. 37097176 4 9 theme serotypes 635:643 arg1 efficiency 600:609 the transduction efficiency 583:609 the transduction efficiency of most recombinant AAV serotypes tested 583:650 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 12 10 theme common 2172:2177 arg1 protease 2193:2200 a common intracellular protease 2170:2200 a common intracellular protease 2170:2200 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 13 11 theme AAV 2458:2460 arg1 serotypes 2462:2470 certain recombinant AAV serotypes 2438:2470 certain recombinant AAV serotypes 2438:2470 Based on the findings, we postulate that differential expression of furin in host cells and tissues is likely to influence gene expression by certain recombinant AAV serotypes. 37097176 2 12 theme AAV 281:283 arg1 serotypes 285:293 several AAV serotypes 273:293 several AAV serotypes 273:293 During the course of infection, several AAV serotypes have been shown to transit through the trans-Golgi network within the host cell. 37097176 5 13 theme AAV4 841:844 arg1 binding 846:852 AAV4 binding 841:852 AAV4 binding 841:852 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 4 14 theme ~2 710:711 arg1 expression 698:707 transgene expression 688:707 transgene expression (~2 log orders) 688:723 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 4 14 theme ~2 710:711 arg1 orders 717:722 ~2 log orders 710:722 ~2 log orders 710:722 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 8 15 dep blockade 1534:1541 arg1 ii 1520:1521 ii 1520:1521 ii 1520:1521 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 11 16 theme interactions 2050:2061 arg1 knowledge 2023:2031 our knowledge 2019:2031 our knowledge of AAV-host cell interactions 2019:2061 Continuing to improve our knowledge of AAV-host cell interactions is critical for improving the safety and efficacy. 37097176 12 17 theme cell 2284:2287 arg1 entry 2289:2293 cell entry 2284:2293 cell entry 2284:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 13 18 theme certain 2438:2444 arg1 serotypes 2462:2470 certain recombinant AAV serotypes 2438:2470 certain recombinant AAV serotypes 2438:2470 Based on the findings, we postulate that differential expression of furin in host cells and tissues is likely to influence gene expression by certain recombinant AAV serotypes. 37097176 5 19 theme KO 908:909 arg1 cells 911:915 furin KO cells 902:915 furin KO cells 902:915 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 6 20 theme Recombinant 992:1002 arg1 furin 1004:1008 Recombinant furin 992:1008 Recombinant furin 992:1008 Recombinant furin does not cleave AAV4 capsid proteins nor alter cellular expression levels of essential factors such as AAVR or GPR108. 37097176 7 21 theme cells 1286:1290 arg1 surface 1244:1250 surface 1244:1250 surface 1244:1250 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 7 21 theme cells 1286:1290 arg1 space 1268:1272 perinuclear space 1256:1272 perinuclear space 1256:1272 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 8 22 theme essential 1297:1305 arg1 nature 1307:1312 The essential nature 1293:1312 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction 1293:1397 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 7 23 theme sialoglycan 1216:1226 arg1 staining 1228:1235 2,3-O-linked sialoglycan staining 1203:1235 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells 1203:1290 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 5 24 theme transcript 867:876 arg1 levels 878:883 transcript levels 867:883 transcript levels 867:883 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 12 25 theme viral 2255:2259 arg1 sialoglycans 2228:2239 certain cell surface sialoglycans 2207:2239 certain cell surface sialoglycans that serve as viral attachment factors for cell entry 2207:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 12 25 theme viral 2255:2259 arg1 factors 2272:2278 viral attachment factors 2255:2278 viral attachment factors for cell entry 2255:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 1 26 theme DNA 167:169 arg1 viruses 107:113 Adeno-associated viruses 90:113 Adeno-associated viruses (AAVs) 90:120 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 1 26 theme DNA 167:169 arg1 viruses 171:177 small, helper-dependent, single-stranded DNA viruses 126:177 small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry 126:238 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 1 27 dep small 126:130 arg1 single-stranded 151:165 single-stranded 151:165 single-stranded 151:165 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 1 27 dep small 126:130 arg1 helper-dependent 133:148 helper-dependent 133:148 helper-dependent 133:148 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 5 28 theme postentry 922:930 arg1 entry 967:971 nuclear entry 959:971 nuclear entry 959:971 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 5 28 theme postentry 922:930 arg1 steps 932:936 postentry steps 922:936 postentry steps such as uncoating or nuclear entry 922:971 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 5 28 theme postentry 922:930 arg1 uncoating 946:954 uncoating 946:954 uncoating 946:954 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 7 29 theme marked 1184:1189 arg1 increase 1191:1198 a marked increase 1182:1198 a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells 1182:1290 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 9 30 theme sialoglycans 1760:1771 arg1 expression 1737:1746 expression 1737:1746 expression 1737:1746 Based on the overall findings, we postulate that furin likely plays a key role in regulating expression of cellular sialoglycans, which in turn can influence permissivity to AAVs and possibly other viruses. 37097176 8 31 theme lion 1506:1509 arg1 AAV 1511:1513 sea lion AAV 1502:1513 sea lion AAV 1502:1513 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 12 32 theme surface 2220:2226 arg1 sialoglycans 2228:2239 certain cell surface sialoglycans 2207:2239 certain cell surface sialoglycans that serve as viral attachment factors for cell entry 2207:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 12 32 theme surface 2220:2226 arg1 factors 2272:2278 viral attachment factors 2255:2278 viral attachment factors for cell entry 2255:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 4 33 theme Furin 553:557 arg1 gene 559:562 the Furin gene 549:562 the Furin gene 549:562 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 0 34 theme Cell 78:81 arg1 Entry 83:87 Adeno-Associated Viral Cell Entry 55:87 Adeno-Associated Viral Cell Entry 55:87 Interplay between Furin and Sialoglycans in Modulating Adeno-Associated Viral Cell Entry. 37097176 8 35 theme KO 1359:1360 arg1 cells 1362:1366 furin KO cells 1353:1366 furin KO cells 1353:1366 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 2 36 theme host 365:368 arg1 cell 370:373 the host cell 361:373 the host cell 361:373 During the course of infection, several AAV serotypes have been shown to transit through the trans-Golgi network within the host cell. 37097176 7 37 theme lectin 1156:1161 arg1 screening 1163:1171 fluorescent lectin screening 1144:1171 fluorescent lectin screening 1144:1171 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 5 38 theme nuclear 959:965 arg1 entry 967:971 nuclear entry 959:971 nuclear entry 959:971 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 6 39 theme capsid 1031:1036 arg1 proteins 1038:1045 AAV4 capsid proteins 1026:1045 AAV4 capsid proteins 1026:1045 Recombinant furin does not cleave AAV4 capsid proteins nor alter cellular expression levels of essential factors such as AAVR or GPR108. 37097176 4 40 theme African 733:739 arg1 AAV4 762:765 the African green monkey isolate AAV4 729:765 the African green monkey isolate AAV4 729:765 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 5 41 theme infectious 808:817 arg1 pathway 819:825 the infectious pathway 804:825 the infectious pathway 804:825 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 7 42 dep surface 1244:1250 arg1 the 1240:1242 the 1240:1242 the 1240:1242 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 3 43 theme current 383:389 arg1 study 391:395 the current study 379:395 the current study 379:395 In the current study, we investigated whether the Golgi-localized, calcium-dependent protease furin influences AAV transduction. 37097176 8 44 theme selective 1524:1532 arg1 blockade 1534:1541 (ii) selective blockade 1519:1541 (ii) selective blockade 1519:1541 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 8 45 theme AAV4 1381:1384 arg1 transduction 1386:1397 AAV4 transduction 1381:1397 AAV4 transduction 1381:1397 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 7 46 theme KO 1283:1284 arg1 cells 1286:1290 furin KO cells 1277:1290 furin KO cells 1277:1290 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 0 47 theme Viral 72:76 arg1 Entry 83:87 Adeno-Associated Viral Cell Entry 55:87 Adeno-Associated Viral Cell Entry 55:87 Interplay between Furin and Sialoglycans in Modulating Adeno-Associated Viral Cell Entry. 37097176 5 48 theme different 785:793 arg1 steps 795:799 different steps 785:799 different steps 785:799 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 10 49 theme Adeno-associated 1862:1877 arg1 AAVs 1888:1891 AAVs 1888:1891 AAVs 1888:1891 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 10 49 theme Adeno-associated 1862:1877 arg1 viruses 1879:1885 Adeno-associated viruses 1862:1885 IMPORTANCE Adeno-associated viruses (AAVs) 1851:1892 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 3 50 theme protease 461:468 arg1 furin 470:474 the Golgi-localized, calcium-dependent protease furin 422:474 the Golgi-localized, calcium-dependent protease furin 422:474 In the current study, we investigated whether the Golgi-localized, calcium-dependent protease furin influences AAV transduction. 37097176 8 51 from expression 1339:1348 arg1 cells 1362:1366 furin KO cells 1353:1366 furin KO cells 1353:1366 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 1 52 theme factors 217:223 arg1 spectrum 200:207 a broad spectrum 192:207 a broad spectrum of host factors for cell entry 192:238 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 3 53 dep Golgi-localized 426:440 arg1 calcium-dependent 443:459 calcium-dependent 443:459 calcium-dependent 443:459 In the current study, we investigated whether the Golgi-localized, calcium-dependent protease furin influences AAV transduction. 37097176 7 54 theme perinuclear 1256:1266 arg1 space 1268:1272 perinuclear space 1256:1272 perinuclear space 1256:1272 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 9 55 theme other 1836:1840 arg1 viruses 1842:1848 other viruses 1836:1848 other viruses 1836:1848 Based on the overall findings, we postulate that furin likely plays a key role in regulating expression of cellular sialoglycans, which in turn can influence permissivity to AAVs and possibly other viruses. 37097176 8 56 theme 2,3-O-linked 1566:1577 arg1 sialoglycans 1579:1590 cellular 2,3-O-linked sialoglycans 1557:1590 cellular 2,3-O-linked sialoglycans 1557:1590 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 1 57 theme cell 229:232 arg1 entry 234:238 cell entry 229:238 cell entry 229:238 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 13 58 theme differential 2337:2348 arg1 expression 2350:2359 differential expression 2337:2359 differential expression of furin in host cells and tissues 2337:2394 Based on the findings, we postulate that differential expression of furin in host cells and tissues is likely to influence gene expression by certain recombinant AAV serotypes. 37097176 4 59 theme most 614:617 arg1 serotypes 635:643 most recombinant AAV serotypes 614:643 most recombinant AAV serotypes tested 614:650 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 2 60 theme trans-Golgi 334:344 arg1 network 346:352 the trans-Golgi network 330:352 the trans-Golgi network within the host cell 330:373 During the course of infection, several AAV serotypes have been shown to transit through the trans-Golgi network within the host cell. 37097176 8 61 from cells 1362:1366 arg1 nature 1307:1312 The essential nature 1293:1312 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction 1293:1397 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 7 62 from staining 1228:1235 arg1 surface 1244:1250 surface 1244:1250 surface 1244:1250 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 7 62 from staining 1228:1235 arg1 space 1268:1272 perinuclear space 1256:1272 perinuclear space 1256:1272 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 6 63 theme cellular 1057:1064 arg1 levels 1077:1082 cellular expression levels 1057:1082 cellular expression levels of essential factors such as AAVR or GPR108 1057:1126 Recombinant furin does not cleave AAV4 capsid proteins nor alter cellular expression levels of essential factors such as AAVR or GPR108. 37097176 2 64 theme several 273:279 arg1 serotypes 285:293 several AAV serotypes 273:293 several AAV serotypes 273:293 During the course of infection, several AAV serotypes have been shown to transit through the trans-Golgi network within the host cell. 37097176 4 65 from increase 676:683 arg1 expression 698:707 transgene expression 688:707 transgene expression (~2 log orders) 688:723 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 4 65 from increase 676:683 arg1 orders 717:722 ~2 log orders 710:722 ~2 log orders 710:722 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 10 66 theme recombinant 1907:1917 arg1 IMPORTANCE 1851:1860 IMPORTANCE Adeno-associated viruses (AAVs) 1851:1892 IMPORTANCE Adeno-associated viruses (AAVs) 1851:1892 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 10 66 theme recombinant 1907:1917 arg1 platform 1926:1933 a proven recombinant vector platform 1898:1933 a proven recombinant vector platform for gene therapy 1898:1950 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 2 67 theme infection 262:270 arg1 course 252:257 the course 248:257 the course of infection 248:270 During the course of infection, several AAV serotypes have been shown to transit through the trans-Golgi network within the host cell. 37097176 12 68 theme current 2118:2124 arg1 study 2126:2130 The current study 2114:2130 The current study 2114:2130 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 9 69 theme overall 1657:1663 arg1 findings 1665:1672 the overall findings 1653:1672 the overall findings 1653:1672 Based on the overall findings, we postulate that furin likely plays a key role in regulating expression of cellular sialoglycans, which in turn can influence permissivity to AAVs and possibly other viruses. 37097176 7 70 from space 1268:1272 arg1 increase 1191:1198 a marked increase 1182:1198 a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells 1182:1290 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 13 71 theme host 2373:2376 arg1 cells 2378:2382 host cells 2373:2382 host cells 2373:2382 Based on the findings, we postulate that differential expression of furin in host cells and tissues is likely to influence gene expression by certain recombinant AAV serotypes. 37097176 10 72 theme gene 1939:1942 arg1 therapy 1944:1950 gene therapy 1939:1950 gene therapy 1939:1950 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 13 73 theme recombinant 2446:2456 arg1 serotypes 2462:2470 certain recombinant AAV serotypes 2438:2470 certain recombinant AAV serotypes 2438:2470 Based on the findings, we postulate that differential expression of furin in host cells and tissues is likely to influence gene expression by certain recombinant AAV serotypes. 37097176 7 74 link 2,3-O-linked 1203:1214 arg1 staining 1228:1235 2,3-O-linked sialoglycan staining 1203:1235 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells 1203:1290 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 1 75 theme broad 194:198 arg1 spectrum 200:207 a broad spectrum 192:207 a broad spectrum of host factors for cell entry 192:238 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 11 76 theme cell 2045:2048 arg1 interactions 2050:2061 AAV-host cell interactions 2036:2061 AAV-host cell interactions 2036:2061 Continuing to improve our knowledge of AAV-host cell interactions is critical for improving the safety and efficacy. 37097176 4 77 theme AAV 631:633 arg1 serotypes 635:643 most recombinant AAV serotypes 614:643 most recombinant AAV serotypes tested 614:650 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 8 78 theme sialoglycan 1327:1337 arg1 expression 1339:1348 increased sialoglycan expression 1317:1348 increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction 1317:1397 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 7 79 from increase 1191:1198 arg1 staining 1228:1235 2,3-O-linked sialoglycan staining 1203:1235 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells 1203:1290 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 7 79 from increase 1191:1198 arg1 surface 1244:1250 surface 1244:1250 surface 1244:1250 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 7 79 from increase 1191:1198 arg1 space 1268:1272 perinuclear space 1256:1272 perinuclear space 1256:1272 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 8 80 link 2,3-O-linked 1566:1577 arg1 sialoglycans 1579:1590 cellular 2,3-O-linked sialoglycans 1557:1590 cellular 2,3-O-linked sialoglycans 1557:1590 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 12 81 theme cell 2215:2218 arg1 sialoglycans 2228:2239 certain cell surface sialoglycans 2207:2239 certain cell surface sialoglycans that serve as viral attachment factors for cell entry 2207:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 12 81 theme cell 2215:2218 arg1 factors 2272:2278 viral attachment factors 2255:2278 viral attachment factors for cell entry 2255:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 1 82 theme small 126:130 arg1 viruses 107:113 Adeno-associated viruses 90:113 Adeno-associated viruses (AAVs) 90:120 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 1 82 theme small 126:130 arg1 viruses 171:177 small, helper-dependent, single-stranded DNA viruses 126:177 small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry 126:238 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 9 83 theme key 1714:1716 arg1 role 1718:1721 a key role 1712:1721 a key role 1712:1721 Based on the overall findings, we postulate that furin likely plays a key role in regulating expression of cellular sialoglycans, which in turn can influence permissivity to AAVs and possibly other viruses. 37097176 8 84 theme related 1469:1475 arg1 isolates 1477:1484 the closely related isolates 1457:1484 the closely related isolates 1457:1484 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 4 85 theme monkey 747:752 arg1 AAV4 762:765 the African green monkey isolate AAV4 729:765 the African green monkey isolate AAV4 729:765 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 4 86 theme log 713:715 arg1 expression 698:707 transgene expression 688:707 transgene expression (~2 log orders) 688:723 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 4 86 theme log 713:715 arg1 orders 717:722 ~2 log orders 710:722 ~2 log orders 710:722 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 7 87 theme 2,3-O-linked 1203:1214 arg1 staining 1228:1235 2,3-O-linked sialoglycan staining 1203:1235 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells 1203:1290 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 12 88 theme attachment 2261:2270 arg1 sialoglycans 2228:2239 certain cell surface sialoglycans 2207:2239 certain cell surface sialoglycans that serve as viral attachment factors for cell entry 2207:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 12 88 theme attachment 2261:2270 arg1 factors 2272:2278 viral attachment factors 2255:2278 viral attachment factors for cell entry 2255:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 10 89 dep IMPORTANCE 1851:1860 arg1 AAVs 1888:1891 AAVs 1888:1891 AAVs 1888:1891 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 10 89 dep IMPORTANCE 1851:1860 arg1 viruses 1879:1885 Adeno-associated viruses 1862:1885 IMPORTANCE Adeno-associated viruses (AAVs) 1851:1892 IMPORTANCE Adeno-associated viruses (AAVs) are a proven recombinant vector platform for gene therapy and have demonstrated success in the clinic. 37097176 8 90 theme sea 1502:1504 arg1 AAV 1511:1513 sea lion AAV 1502:1513 sea lion AAV 1502:1513 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 4 91 theme transgene 688:696 arg1 expression 698:707 transgene expression 688:707 transgene expression (~2 log orders) 688:723 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 4 91 theme transgene 688:696 arg1 orders 717:722 ~2 log orders 710:722 ~2 log orders 710:722 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 5 92 from Interrogation 768:780 arg1 pathway 819:825 the infectious pathway 804:825 the infectious pathway 804:825 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 9 93 theme cellular 1751:1758 arg1 sialoglycans 1760:1771 cellular sialoglycans 1751:1771 cellular sialoglycans 1751:1771 Based on the overall findings, we postulate that furin likely plays a key role in regulating expression of cellular sialoglycans, which in turn can influence permissivity to AAVs and possibly other viruses. 37097176 12 94 theme certain 2207:2213 arg1 sialoglycans 2228:2239 certain cell surface sialoglycans 2207:2239 certain cell surface sialoglycans that serve as viral attachment factors for cell entry 2207:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 12 94 theme certain 2207:2213 arg1 factors 2272:2278 viral attachment factors 2255:2278 viral attachment factors for cell entry 2255:2293 The current study dissects the interplay between furin, a common intracellular protease, and certain cell surface sialoglycans that serve as viral attachment factors for cell entry. 37097176 8 95 theme increased 1317:1325 arg1 expression 1339:1348 increased sialoglycan expression 1317:1348 increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction 1317:1397 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 4 96 theme green 741:745 arg1 AAV4 762:765 the African green monkey isolate AAV4 729:765 the African green monkey isolate AAV4 729:765 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 6 97 theme essential 1087:1095 arg1 GPR108 1121:1126 GPR108 1121:1126 GPR108 1121:1126 Recombinant furin does not cleave AAV4 capsid proteins nor alter cellular expression levels of essential factors such as AAVR or GPR108. 37097176 6 97 theme essential 1087:1095 arg1 factors 1097:1103 essential factors 1087:1103 essential factors such as AAVR or GPR108 1087:1126 Recombinant furin does not cleave AAV4 capsid proteins nor alter cellular expression levels of essential factors such as AAVR or GPR108. 37097176 6 97 theme essential 1087:1095 arg1 AAVR 1113:1116 AAVR 1113:1116 AAVR 1113:1116 Recombinant furin does not cleave AAV4 capsid proteins nor alter cellular expression levels of essential factors such as AAVR or GPR108. 37097176 5 98 theme furin 902:906 arg1 cells 911:915 furin KO cells 902:915 furin KO cells 902:915 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 8 99 theme expression 1339:1348 arg1 nature 1307:1312 The essential nature 1293:1312 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction 1293:1397 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 5 100 theme steps 795:799 arg1 Interrogation 768:780 Interrogation 768:780 Interrogation of different steps in the infectious pathway 768:825 Interrogation of different steps in the infectious pathway revealed that AAV4 binding, uptake, and transcript levels are increased in furin KO cells, but postentry steps such as uncoating or nuclear entry remain unaffected. 37097176 8 101 from nature 1307:1312 arg1 cells 1362:1366 furin KO cells 1353:1366 furin KO cells 1353:1366 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 1 102 theme Adeno-associated 90:105 arg1 viruses 107:113 Adeno-associated viruses 90:113 Adeno-associated viruses (AAVs) 90:120 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 1 102 theme Adeno-associated 90:105 arg1 viruses 171:177 small, helper-dependent, single-stranded DNA viruses 126:177 small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry 126:238 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 1 102 theme Adeno-associated 90:105 arg1 AAVs 116:119 AAVs 116:119 AAVs 116:119 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 8 103 theme furin 1353:1357 arg1 cells 1362:1366 furin KO cells 1353:1366 furin KO cells 1353:1366 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 6 104 theme AAV4 1026:1029 arg1 proteins 1038:1045 AAV4 capsid proteins 1026:1045 AAV4 capsid proteins 1026:1045 Recombinant furin does not cleave AAV4 capsid proteins nor alter cellular expression levels of essential factors such as AAVR or GPR108. 37097176 4 105 theme gene 559:562 arg1 KO 542:543 KO 542:543 KO 542:543 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 4 105 theme gene 559:562 arg1 knockout 532:539 knockout 532:539 knockout 532:539 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 13 106 from expression 2350:2359 arg1 tissues 2388:2394 tissues 2388:2394 tissues 2388:2394 Based on the findings, we postulate that differential expression of furin in host cells and tissues is likely to influence gene expression by certain recombinant AAV serotypes. 37097176 13 106 from expression 2350:2359 arg1 cells 2378:2382 host cells 2373:2382 host cells 2373:2382 Based on the findings, we postulate that differential expression of furin in host cells and tissues is likely to influence gene expression by certain recombinant AAV serotypes. 37097176 7 107 theme furin 1277:1281 arg1 cells 1286:1290 furin KO cells 1277:1290 furin KO cells 1277:1290 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 37097176 4 108 theme recombinant 619:629 arg1 serotypes 635:643 most recombinant AAV serotypes 614:643 most recombinant AAV serotypes tested 614:650 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 3 109 theme Golgi-localized 426:440 arg1 furin 470:474 the Golgi-localized, calcium-dependent protease furin 422:474 the Golgi-localized, calcium-dependent protease furin 422:474 In the current study, we investigated whether the Golgi-localized, calcium-dependent protease furin influences AAV transduction. 37097176 0 110 theme Adeno-Associated 55:70 arg1 Entry 83:87 Adeno-Associated Viral Cell Entry 55:87 Adeno-Associated Viral Cell Entry 55:87 Interplay between Furin and Sialoglycans in Modulating Adeno-Associated Viral Cell Entry. 37097176 8 111 dep increased 1431:1439 arg1 i 1428:1428 i 1428:1428 i 1428:1428 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 13 112 theme furin 2364:2368 arg1 expression 2350:2359 differential expression 2337:2359 differential expression of furin in host cells and tissues 2337:2394 Based on the findings, we postulate that differential expression of furin in host cells and tissues is likely to influence gene expression by certain recombinant AAV serotypes. 37097176 8 113 theme cellular 1557:1564 arg1 sialoglycans 1579:1590 cellular 2,3-O-linked sialoglycans 1557:1590 cellular 2,3-O-linked sialoglycans 1557:1590 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 3 114 theme AAV 487:489 arg1 transduction 491:502 AAV transduction 487:502 AAV transduction 487:502 In the current study, we investigated whether the Golgi-localized, calcium-dependent protease furin influences AAV transduction. 37097176 6 115 theme factors 1097:1103 arg1 levels 1077:1082 cellular expression levels 1057:1082 cellular expression levels of essential factors such as AAVR or GPR108 1057:1126 Recombinant furin does not cleave AAV4 capsid proteins nor alter cellular expression levels of essential factors such as AAVR or GPR108. 37097176 8 116 theme sialoglycans 1579:1590 arg1 removal 1546:1552 removal 1546:1552 removal of cellular 2,3-O-linked sialoglycans by specific lectins 1546:1610 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 8 116 theme sialoglycans 1579:1590 arg1 blockade 1534:1541 (ii) selective blockade 1519:1541 (ii) selective blockade 1519:1541 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 8 116 theme sialoglycans 1579:1590 arg1 neuraminidase 1615:1627 neuraminidase 1615:1627 neuraminidase 1615:1627 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 8 116 theme sialoglycans 1579:1590 arg1 AAVrh.32.33 1486:1496 AAVrh.32.33 1486:1496 AAVrh.32.33 1486:1496 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 8 116 theme sialoglycans 1579:1590 arg1 AAV 1511:1513 sea lion AAV 1502:1513 sea lion AAV 1502:1513 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 4 117 theme isolate 754:760 arg1 AAV4 762:765 the African green monkey isolate AAV4 729:765 the African green monkey isolate AAV4 729:765 While CRISPR/Cas9-mediated knockout (KO) of the Furin gene minimally affected the transduction efficiency of most recombinant AAV serotypes tested, we observed a striking increase in transgene expression (~2 log orders) for the African green monkey isolate AAV4. 37097176 1 118 theme host 212:215 arg1 factors 217:223 host factors 212:223 host factors 212:223 Adeno-associated viruses (AAVs) are small, helper-dependent, single-stranded DNA viruses that exploit a broad spectrum of host factors for cell entry. 37097176 8 119 theme specific 1595:1602 arg1 lectins 1604:1610 specific lectins 1595:1610 specific lectins 1595:1610 The essential nature of increased sialoglycan expression in furin KO cells in enhancing AAV4 transduction was further corroborated by (i) increased transduction by the closely related isolates AAVrh.32.33 and sea lion AAV and (ii) selective blockade or removal of cellular 2,3-O-linked sialoglycans by specific lectins or neuraminidase, respectively. 37097176 7 120 theme fluorescent 1144:1154 arg1 screening 1163:1171 fluorescent lectin screening 1144:1171 fluorescent lectin screening 1144:1171 Interestingly, fluorescent lectin screening revealed a marked increase in 2,3-O-linked sialoglycan staining on the surface and perinuclear space of furin KO cells. 35929395 0 0 theme ductal 106:111 arg1 adenocarcinoma 113:126 pancreatic ductal adenocarcinoma 95:126 pancreatic ductal adenocarcinoma 95:126 Synthetic oleanane triterpenoid derivative CDDO-Me disrupts cellular bioenergetics to suppress pancreatic ductal adenocarcinoma via targeting SLC1A5. 35929395 1 1 theme nude 370:373 arg1 mice 375:378 xenograft nude mice 360:378 xenograft nude mice 360:378 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 5 2 theme induced 853:859 arg1 respiration 875:885 induced mitochondrial respiration 853:885 induced mitochondrial respiration 853:885 Mechanistically, we demonstrated CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction. 35929395 11 3 theme novel 1768:1772 arg1 biomarker 1774:1782 a novel biomarker 1766:1782 a novel biomarker for PDAC patients 1766:1800 Our data highlights CDDO-Me could be considered a potential compound for PDAC therapy, and SLC1A5 could be a novel biomarker for PDAC patients. 35929395 11 3 theme novel 1768:1772 arg1 SLC1A5 1750:1755 SLC1A5 1750:1755 SLC1A5 1750:1755 Our data highlights CDDO-Me could be considered a potential compound for PDAC therapy, and SLC1A5 could be a novel biomarker for PDAC patients. 35929395 4 4 theme CDDO-Me 776:782 arg1 activity 764:771 the strong antitumor activity 743:771 the strong antitumor activity of CDDO-Me in suppressing PDAC growth 743:809 We confirmed the strong antitumor activity of CDDO-Me in suppressing PDAC growth. 35929395 1 5 theme pancreatic 291:300 arg1 PDAC 325:328 PDAC 325:328 PDAC 325:328 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 1 5 theme pancreatic 291:300 arg1 adenocarcinoma 309:322 pancreatic ductal adenocarcinoma 291:322 pancreatic ductal adenocarcinoma (PDAC) 291:329 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 2 6 theme aerobic 511:517 arg1 glycolysis 519:528 aerobic glycolysis 511:528 aerobic glycolysis 511:528 Seahorse XFe96 bioenergetics analyzer was applied to determine aerobic glycolysis and mitochondrial respiration. 35929395 11 7 theme PDAC 1788:1791 arg1 patients 1793:1800 PDAC patients 1788:1800 PDAC patients 1788:1800 Our data highlights CDDO-Me could be considered a potential compound for PDAC therapy, and SLC1A5 could be a novel biomarker for PDAC patients. 35929395 9 8 theme patients 1422:1429 arg1 prognosis 1404:1412 the poor prognosis 1395:1412 the poor prognosis of PDAC patients 1395:1429 Finally, we confirmed SLC1A5 was significantly overexpressed in PDAC and closely correlated with the poor prognosis of PDAC patients. 35929395 1 9 from activity 189:196 arg1 PDAC 325:328 PDAC 325:328 PDAC 325:328 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 1 9 from activity 189:196 arg1 adenocarcinoma 309:322 pancreatic ductal adenocarcinoma 291:322 pancreatic ductal adenocarcinoma (PDAC) 291:329 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 6 10 theme transporter 972:982 arg1 SLC1A5 984:989 CDDO-Me downregulated glutamine transporter SLC1A5 940:989 CDDO-Me downregulated glutamine transporter SLC1A5 940:989 We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. 35929395 1 11 theme ductal 302:307 arg1 PDAC 325:328 PDAC 325:328 PDAC 325:328 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 1 11 theme ductal 302:307 arg1 adenocarcinoma 309:322 pancreatic ductal adenocarcinoma 291:322 pancreatic ductal adenocarcinoma (PDAC) 291:329 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 6 12 theme species  1031:1038 arg1 levels 1045:1050 excessive reactive oxygen species (ROS) levels 1005:1050 excessive reactive oxygen species (ROS) levels that suppressed tumor growth 1005:1079 We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. 35929395 3 13 theme enzymes 721:727 arg1 transcripts 685:695 messenger RNA transcripts 671:695 messenger RNA transcripts 671:695 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 3 13 theme enzymes 721:727 arg1 protein 659:665 protein 659:665 protein 659:665 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 3 14 theme reverse 591:597 arg1 reactions 630:638 reverse transcription-polymerase chain reactions 591:638 reverse transcription-polymerase chain reactions 591:638 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 6 15 theme oxygen 1024:1029 arg1 levels 1045:1050 excessive reactive oxygen species (ROS) levels 1005:1050 excessive reactive oxygen species (ROS) levels that suppressed tumor growth 1005:1079 We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. 35929395 3 16 theme transcription-polymerase 599:622 arg1 reactions 630:638 reverse transcription-polymerase chain reactions 591:638 reverse transcription-polymerase chain reactions 591:638 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 4 17 theme PDAC 799:802 arg1 growth 804:809 PDAC growth 799:809 PDAC growth 799:809 We confirmed the strong antitumor activity of CDDO-Me in suppressing PDAC growth. 35929395 5 18 theme mitochondrial 861:873 arg1 respiration 875:885 induced mitochondrial respiration 853:885 induced mitochondrial respiration 853:885 Mechanistically, we demonstrated CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction. 35929395 6 19 theme reactive 1015:1022 arg1 levels 1045:1050 excessive reactive oxygen species (ROS) levels 1005:1050 excessive reactive oxygen species (ROS) levels that suppressed tumor growth 1005:1079 We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. 35929395 10 20 theme PDAC 1646:1649 arg1 growth 1651:1656 PDAC growth 1646:1656 PDAC growth 1646:1656 Our work uncovers CDDO-Me is effective at suppressing PDAC cell growth in vitro and in vivo and illuminates CDDO-Me caused excessive ROS and cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth. 35929395 8 21 theme protease-mediated 1267:1283 arg1 degradation 1285:1295 protease-mediated degradation 1267:1295 protease-mediated degradation 1267:1295 We also found CDDO-Me could inhibit N-linked glycosylation of SLC1A5, which promotes protease-mediated degradation. 35929395 5 22 theme glycolysis 899:908 arg1 dysfunction 910:920 CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction 845:920 CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction 845:920 Mechanistically, we demonstrated CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction. 35929395 6 23 theme excessive 1005:1013 arg1 levels 1045:1050 excessive reactive oxygen species (ROS) levels 1005:1050 excessive reactive oxygen species (ROS) levels that suppressed tumor growth 1005:1079 We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. 35929395 10 24 theme cellular 1573:1580 arg1 bioenergetics 1582:1594 cellular bioenergetics 1573:1594 cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth 1573:1656 Our work uncovers CDDO-Me is effective at suppressing PDAC cell growth in vitro and in vivo and illuminates CDDO-Me caused excessive ROS and cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth. 35929395 2 25 theme bioenergetics 463:475 arg1 analyzer 477:484 Seahorse XFe96 bioenergetics analyzer 448:484 Seahorse XFe96 bioenergetics analyzer 448:484 Seahorse XFe96 bioenergetics analyzer was applied to determine aerobic glycolysis and mitochondrial respiration. 35929395 8 26 gly glycosylation 1227:1239 arg1 SLC1A5 1244:1249 SLC1A5 1244:1249 SLC1A5 1244:1249 We also found CDDO-Me could inhibit N-linked glycosylation of SLC1A5, which promotes protease-mediated degradation. 35929395 1 27 theme triterpenoid 211:222 arg1 activity 189:196 the potential antitumor activity 165:196 the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC) 165:329 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 0 28 theme oleanane 10:17 arg1 CDDO-Me 43:49 Synthetic oleanane triterpenoid derivative CDDO-Me 0:49 Synthetic oleanane triterpenoid derivative CDDO-Me 0:49 Synthetic oleanane triterpenoid derivative CDDO-Me disrupts cellular bioenergetics to suppress pancreatic ductal adenocarcinoma via targeting SLC1A5. 35929395 1 29 dep assay 349:353 arg1 assay 380:384 assay 380:384 assay 380:384 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 4 30 theme strong 747:752 arg1 activity 764:771 the strong antitumor activity 743:771 the strong antitumor activity of CDDO-Me in suppressing PDAC growth 743:809 We confirmed the strong antitumor activity of CDDO-Me in suppressing PDAC growth. 35929395 0 31 theme Synthetic 0:8 arg1 CDDO-Me 43:49 Synthetic oleanane triterpenoid derivative CDDO-Me 0:49 Synthetic oleanane triterpenoid derivative CDDO-Me 0:49 Synthetic oleanane triterpenoid derivative CDDO-Me disrupts cellular bioenergetics to suppress pancreatic ductal adenocarcinoma via targeting SLC1A5. 35929395 11 32 theme potential 1709:1717 arg1 compound 1719:1726 a potential compound 1707:1726 a potential compound for PDAC therapy 1707:1743 Our data highlights CDDO-Me could be considered a potential compound for PDAC therapy, and SLC1A5 could be a novel biomarker for PDAC patients. 35929395 9 33 dep confirmed 1310:1318 arg1 overexpressed 1345:1357 overexpressed 1345:1357 was significantly overexpressed in PDAC 1327:1365 Finally, we confirmed SLC1A5 was significantly overexpressed in PDAC and closely correlated with the poor prognosis of PDAC patients. 35929395 9 33 dep confirmed 1310:1318 arg1 correlated 1379:1388 correlated 1379:1388 closely correlated with the poor prognosis of PDAC patients 1371:1429 Finally, we confirmed SLC1A5 was significantly overexpressed in PDAC and closely correlated with the poor prognosis of PDAC patients. 35929395 0 34 theme derivative 32:41 arg1 CDDO-Me 43:49 Synthetic oleanane triterpenoid derivative CDDO-Me 0:49 Synthetic oleanane triterpenoid derivative CDDO-Me 0:49 Synthetic oleanane triterpenoid derivative CDDO-Me disrupts cellular bioenergetics to suppress pancreatic ductal adenocarcinoma via targeting SLC1A5. 35929395 8 35 theme N-linked 1218:1225 arg1 glycosylation 1227:1239 N-linked glycosylation 1218:1239 N-linked glycosylation 1218:1239 We also found CDDO-Me could inhibit N-linked glycosylation of SLC1A5, which promotes protease-mediated degradation. 35929395 10 36 theme excessive 1555:1563 arg1 ROS 1565:1567 excessive ROS 1555:1567 excessive ROS 1555:1567 Our work uncovers CDDO-Me is effective at suppressing PDAC cell growth in vitro and in vivo and illuminates CDDO-Me caused excessive ROS and cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth. 35929395 3 37 theme chain 624:628 arg1 reactions 630:638 reverse transcription-polymerase chain reactions 591:638 reverse transcription-polymerase chain reactions 591:638 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 7 38 dep confirmed 1095:1103 arg1 reduced 1127:1133 reduced 1127:1133 confirmed that SLC1A5 depletion reduced the ratio of glutathione/oxidized glutathione 1095:1179 Moreover, we confirmed that SLC1A5 depletion reduced the ratio of glutathione/oxidized glutathione. 35929395 2 39 theme Seahorse 448:455 arg1 analyzer 477:484 Seahorse XFe96 bioenergetics analyzer 448:484 Seahorse XFe96 bioenergetics analyzer 448:484 Seahorse XFe96 bioenergetics analyzer was applied to determine aerobic glycolysis and mitochondrial respiration. 35929395 1 40 theme tumor 413:417 arg1 growth 419:424 tumor growth 413:424 tumor growth 413:424 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 3 41 dep blot 569:572 arg1 reactions 630:638 reverse transcription-polymerase chain reactions 591:638 reverse transcription-polymerase chain reactions 591:638 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 6 42 theme ROS 1040:1042 arg1 levels 1045:1050 excessive reactive oxygen species (ROS) levels 1005:1050 excessive reactive oxygen species (ROS) levels that suppressed tumor growth 1005:1079 We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. 35929395 3 43 theme Western 561:567 arg1 blot 569:572 Western blot 561:572 Western blot 561:572 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 5 44 theme respiration 875:885 arg1 dysfunction 910:920 CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction 845:920 CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction 845:920 Mechanistically, we demonstrated CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction. 35929395 1 45 theme MTT 332:334 arg1 assay 349:353 MTT cytotoxicity assay 332:353 MTT cytotoxicity assay 332:353 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 10 46 dep bioenergetics 1582:1594 arg1 inhibited 1636:1644 inhibited 1636:1644 inhibited PDAC growth 1636:1656 Our work uncovers CDDO-Me is effective at suppressing PDAC cell growth in vitro and in vivo and illuminates CDDO-Me caused excessive ROS and cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth. 35929395 1 47 theme cytotoxicity 336:347 arg1 assay 349:353 MTT cytotoxicity assay 332:353 MTT cytotoxicity assay 332:353 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 9 48 theme poor 1399:1402 arg1 prognosis 1404:1412 the poor prognosis 1395:1412 the poor prognosis of PDAC patients 1395:1429 Finally, we confirmed SLC1A5 was significantly overexpressed in PDAC and closely correlated with the poor prognosis of PDAC patients. 35929395 3 49 theme messenger 671:679 arg1 transcripts 685:695 messenger RNA transcripts 671:695 messenger RNA transcripts 671:695 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 5 50 theme aerobic 891:897 arg1 glycolysis 899:908 aerobic glycolysis 891:908 aerobic glycolysis 891:908 Mechanistically, we demonstrated CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction. 35929395 6 51 theme tumor 1068:1072 arg1 growth 1074:1079 tumor growth 1068:1079 tumor growth 1068:1079 We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. 35929395 3 52 theme metabolic 711:719 arg1 enzymes 721:727 metabolic enzymes 711:727 metabolic enzymes 711:727 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 0 53 theme cellular 60:67 arg1 bioenergetics 69:81 cellular bioenergetics 60:81 cellular bioenergetics 60:81 Synthetic oleanane triterpenoid derivative CDDO-Me disrupts cellular bioenergetics to suppress pancreatic ductal adenocarcinoma via targeting SLC1A5. 35929395 8 54 theme SLC1A5 1244:1249 arg1 glycosylation 1227:1239 N-linked glycosylation 1218:1239 N-linked glycosylation 1218:1239 We also found CDDO-Me could inhibit N-linked glycosylation of SLC1A5, which promotes protease-mediated degradation. 35929395 6 55 theme glutamine 962:970 arg1 SLC1A5 984:989 CDDO-Me downregulated glutamine transporter SLC1A5 940:989 CDDO-Me downregulated glutamine transporter SLC1A5 940:989 We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. 35929395 9 56 theme PDAC 1417:1420 arg1 patients 1422:1429 PDAC patients 1417:1429 PDAC patients 1417:1429 Finally, we confirmed SLC1A5 was significantly overexpressed in PDAC and closely correlated with the poor prognosis of PDAC patients. 35929395 10 57 theme cell 1491:1494 arg1 growth 1496:1501 PDAC cell growth 1486:1501 PDAC cell growth 1486:1501 Our work uncovers CDDO-Me is effective at suppressing PDAC cell growth in vitro and in vivo and illuminates CDDO-Me caused excessive ROS and cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth. 35929395 11 58 theme PDAC 1732:1735 arg1 therapy 1737:1743 PDAC therapy 1732:1743 PDAC therapy 1732:1743 Our data highlights CDDO-Me could be considered a potential compound for PDAC therapy, and SLC1A5 could be a novel biomarker for PDAC patients. 35929395 7 59 theme glutathione/oxidized 1148:1167 arg1 glutathione 1169:1179 glutathione/oxidized glutathione 1148:1179 glutathione/oxidized glutathione 1148:1179 Moreover, we confirmed that SLC1A5 depletion reduced the ratio of glutathione/oxidized glutathione. 35929395 6 60 theme downregulated 948:960 arg1 SLC1A5 984:989 CDDO-Me downregulated glutamine transporter SLC1A5 940:989 CDDO-Me downregulated glutamine transporter SLC1A5 940:989 We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. 35929395 10 61 theme PDAC 1486:1489 arg1 growth 1496:1501 PDAC cell growth 1486:1501 PDAC cell growth 1486:1501 Our work uncovers CDDO-Me is effective at suppressing PDAC cell growth in vitro and in vivo and illuminates CDDO-Me caused excessive ROS and cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth. 35929395 7 62 theme glutathione 1169:1179 arg1 ratio 1139:1143 the ratio 1135:1143 the ratio of glutathione/oxidized glutathione 1135:1179 Moreover, we confirmed that SLC1A5 depletion reduced the ratio of glutathione/oxidized glutathione. 35929395 6 63 theme CDDO-Me 940:946 arg1 SLC1A5 984:989 CDDO-Me downregulated glutamine transporter SLC1A5 940:989 CDDO-Me downregulated glutamine transporter SLC1A5 940:989 We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. 35929395 3 64 theme SLC1A5 700:705 arg1 transcripts 685:695 messenger RNA transcripts 671:695 messenger RNA transcripts 671:695 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 3 64 theme SLC1A5 700:705 arg1 protein 659:665 protein 659:665 protein 659:665 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 7 65 theme that SLC1A5 1105:1115 arg1 depletion 1117:1125 that SLC1A5 depletion 1105:1125 that SLC1A5 depletion 1105:1125 Moreover, we confirmed that SLC1A5 depletion reduced the ratio of glutathione/oxidized glutathione. 35929395 4 66 theme antitumor 754:762 arg1 activity 764:771 the strong antitumor activity 743:771 the strong antitumor activity of CDDO-Me in suppressing PDAC growth 743:809 We confirmed the strong antitumor activity of CDDO-Me in suppressing PDAC growth. 35929395 8 67 link N-linked 1218:1225 arg1 glycosylation 1227:1239 N-linked glycosylation 1218:1239 N-linked glycosylation 1218:1239 We also found CDDO-Me could inhibit N-linked glycosylation of SLC1A5, which promotes protease-mediated degradation. 35929395 2 68 theme mitochondrial 534:546 arg1 respiration 548:558 mitochondrial respiration 534:558 mitochondrial respiration 534:558 Seahorse XFe96 bioenergetics analyzer was applied to determine aerobic glycolysis and mitochondrial respiration. 35929395 3 69 theme RNA 681:683 arg1 transcripts 685:695 messenger RNA transcripts 671:695 messenger RNA transcripts 671:695 Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. 35929395 1 70 theme potential 169:177 arg1 activity 189:196 the potential antitumor activity 165:196 the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC) 165:329 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 5 71 theme CDDO-Me 845:851 arg1 dysfunction 910:920 CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction 845:920 CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction 845:920 Mechanistically, we demonstrated CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction. 35929395 1 72 theme xenograft 360:368 arg1 mice 375:378 xenograft nude mice 360:378 xenograft nude mice 360:378 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 0 73 theme triterpenoid 19:30 arg1 CDDO-Me 43:49 Synthetic oleanane triterpenoid derivative CDDO-Me 0:49 Synthetic oleanane triterpenoid derivative CDDO-Me 0:49 Synthetic oleanane triterpenoid derivative CDDO-Me disrupts cellular bioenergetics to suppress pancreatic ductal adenocarcinoma via targeting SLC1A5. 35929395 0 74 theme pancreatic 95:104 arg1 adenocarcinoma 113:126 pancreatic ductal adenocarcinoma 95:126 pancreatic ductal adenocarcinoma 95:126 Synthetic oleanane triterpenoid derivative CDDO-Me disrupts cellular bioenergetics to suppress pancreatic ductal adenocarcinoma via targeting SLC1A5. 35929395 1 75 theme antitumor 179:187 arg1 activity 189:196 the potential antitumor activity 165:196 the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC) 165:329 To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. 35929395 10 76 dep illuminates 1528:1538 arg1 caused 1548:1553 caused 1548:1553 illuminates CDDO-Me caused excessive ROS and cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth 1528:1656 Our work uncovers CDDO-Me is effective at suppressing PDAC cell growth in vitro and in vivo and illuminates CDDO-Me caused excessive ROS and cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth. 37034230 0 0 theme JAK2-STAT3 64:73 arg1 pathway 75:81 JAK2-STAT3 pathway 64:81 JAK2-STAT3 pathway in esophageal squamous cell carcinoma 64:119 Circ8199 encodes a protein that inhibits the activity of OGT by JAK2-STAT3 pathway in esophageal squamous cell carcinoma. 37034230 4 1 theme tumor 458:462 arg1 prognosis 464:472 tumor prognosis 458:472 tumor prognosis 458:472 Our previous studies found that the circ8199 gene is associated with tumor prognosis. 37034230 7 2 theme downstream 943:952 arg1 gene 954:957 its downstream gene 939:957 its downstream gene JAK2 939:962 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 5 3 theme transferase 707:717 arg1 proliferation 630:642 the proliferation 626:642 the proliferation of ESCC cells 626:656 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 5 3 theme transferase 707:717 arg1 activity 666:673 the activity 662:673 the activity of O-linked N-acetylglucosamine transferase (OGT) 662:723 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 7 4 theme gene 954:957 arg1 JAK2 959:962 its downstream gene JAK2 939:962 its downstream gene JAK2 939:962 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 6 5 theme Further 741:747 arg1 experiments 749:759 Further experiments 741:759 Further experiments 741:759 Further experiments demonstrated that circ8199 could interact with OGT, leading to a decrease in OGT's activity. 37034230 7 6 dep stimulated 891:900 arg1 promoting 965:973 promoting 965:973 promoting the O-GlcNAc glycosylation modification of JAK2 965:1021 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 7 6 dep stimulated 891:900 arg1 activating 1027:1036 activating 1027:1036 activating the JAK2-STAT3 pathway 1027:1059 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 0 7 theme squamous 97:104 arg1 carcinoma 111:119 esophageal squamous cell carcinoma 86:119 esophageal squamous cell carcinoma 86:119 Circ8199 encodes a protein that inhibits the activity of OGT by JAK2-STAT3 pathway in esophageal squamous cell carcinoma. 37034230 0 8 theme esophageal 86:95 arg1 carcinoma 111:119 esophageal squamous cell carcinoma 86:119 esophageal squamous cell carcinoma 86:119 Circ8199 encodes a protein that inhibits the activity of OGT by JAK2-STAT3 pathway in esophageal squamous cell carcinoma. 37034230 8 9 theme drug 1178:1181 arg1 discovery 1183:1191 drug discovery 1178:1191 drug discovery 1178:1191 Our study indicated that circ8199 regulates the JAK2-STAT3 pathway through OGT, providing a candidate mechanism for drug discovery and development. 37034230 5 10 from role 498:501 arg1 ESCC 518:521 ESCC 518:521 ESCC 518:521 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 5 11 theme circ8199 593:600 arg1 overexpression 575:588 overexpression 575:588 overexpression of circ8199 575:600 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 3 12 theme important 354:362 arg1 role 364:367 an important role 351:367 an important role 351:367 CircRNA has been proven to play an important role in various cancers. 37034230 0 13 from pathway 75:81 arg1 carcinoma 111:119 esophageal squamous cell carcinoma 86:119 esophageal squamous cell carcinoma 86:119 Circ8199 encodes a protein that inhibits the activity of OGT by JAK2-STAT3 pathway in esophageal squamous cell carcinoma. 37034230 7 14 theme binding 906:912 arg1 activity 914:921 the binding activity 902:921 the binding activity between OGT and its downstream gene JAK2 902:962 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 1 15 with tumor 189:193 arg1 mortality 226:234 mortality 226:234 mortality 226:234 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 1 15 with tumor 189:193 arg1 rate 217:220 a high incidence rate 200:220 a high incidence rate 200:220 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 5 16 theme functional 537:546 arg1 experiments 548:558 functional experiments 537:558 functional experiments 537:558 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 1 17 theme invasive 170:177 arg1 carcinoma 147:155 Esophageal squamous cell carcinoma 122:155 Esophageal squamous cell carcinoma (ESCC) 122:162 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 1 17 theme invasive 170:177 arg1 tumor 189:193 an invasive malignant tumor 167:193 an invasive malignant tumor with a high incidence rate and mortality 167:234 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 7 18 theme JAK2-STAT3 1042:1051 arg1 pathway 1053:1059 the JAK2-STAT3 pathway 1038:1059 the JAK2-STAT3 pathway 1038:1059 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 0 19 theme cell 106:109 arg1 carcinoma 111:119 esophageal squamous cell carcinoma 86:119 esophageal squamous cell carcinoma 86:119 Circ8199 encodes a protein that inhibits the activity of OGT by JAK2-STAT3 pathway in esophageal squamous cell carcinoma. 37034230 1 20 theme malignant 179:187 arg1 carcinoma 147:155 Esophageal squamous cell carcinoma 122:155 Esophageal squamous cell carcinoma (ESCC) 122:162 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 1 20 theme malignant 179:187 arg1 tumor 189:193 an invasive malignant tumor 167:193 an invasive malignant tumor with a high incidence rate and mortality 167:234 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 3 21 theme various 372:378 arg1 cancers 380:386 various cancers 372:386 various cancers 372:386 CircRNA has been proven to play an important role in various cancers. 37034230 5 22 theme O-linked 678:685 arg1 OGT 720:722 OGT 720:722 OGT 720:722 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 5 22 theme O-linked 678:685 arg1 transferase 707:717 O-linked N-acetylglucosamine transferase 678:717 O-linked N-acetylglucosamine transferase (OGT) 678:723 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 5 23 theme N-acetylglucosamine 687:705 arg1 OGT 720:722 OGT 720:722 OGT 720:722 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 5 23 theme N-acetylglucosamine 687:705 arg1 transferase 707:717 O-linked N-acetylglucosamine transferase 678:717 O-linked N-acetylglucosamine transferase (OGT) 678:723 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 6 24 from decrease 826:833 arg1 activity 844:851 OGT's activity 838:851 OGT's activity 838:851 Further experiments demonstrated that circ8199 could interact with OGT, leading to a decrease in OGT's activity. 37034230 8 25 theme candidate 1154:1162 arg1 mechanism 1164:1172 a candidate mechanism 1152:1172 a candidate mechanism for drug discovery and development 1152:1207 Our study indicated that circ8199 regulates the JAK2-STAT3 pathway through OGT, providing a candidate mechanism for drug discovery and development. 37034230 5 26 theme ESCC 647:650 arg1 cells 652:656 ESCC cells 647:656 ESCC cells 647:656 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 5 27 theme circ8199 506:513 arg1 role 498:501 the role 494:501 the role of circ8199 in ESCC 494:521 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 5 28 theme cells 652:656 arg1 proliferation 630:642 the proliferation 626:642 the proliferation of ESCC cells 626:656 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 5 28 theme cells 652:656 arg1 activity 666:673 the activity 662:673 the activity of O-linked N-acetylglucosamine transferase (OGT) 662:723 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 7 29 theme O-GlcNAc 979:986 arg1 modification 1002:1013 the O-GlcNAc glycosylation modification 975:1013 the O-GlcNAc glycosylation modification of JAK2 975:1021 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 7 30 mod modification 1002:1013 arg1 JAK2 1018:1021 JAK2 1018:1021 JAK2 1018:1021 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 7 30 mod modification 1002:1013 arg3 glycosylation 988:1000 the O-GlcNAc glycosylation modification 975:1013 the O-GlcNAc glycosylation modification of JAK2 975:1021 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 7 31 theme JAK2 1018:1021 arg1 modification 1002:1013 the O-GlcNAc glycosylation modification 975:1013 the O-GlcNAc glycosylation modification of JAK2 975:1021 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 1 32 theme squamous 133:140 arg1 tumor 189:193 an invasive malignant tumor 167:193 an invasive malignant tumor with a high incidence rate and mortality 167:234 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 1 32 theme squamous 133:140 arg1 ESCC 158:161 ESCC 158:161 ESCC 158:161 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 1 32 theme squamous 133:140 arg1 carcinoma 147:155 Esophageal squamous cell carcinoma 122:155 Esophageal squamous cell carcinoma (ESCC) 122:162 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 7 33 theme glycosylation 988:1000 arg1 modification 1002:1013 the O-GlcNAc glycosylation modification 975:1013 the O-GlcNAc glycosylation modification of JAK2 975:1021 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 2 34 theme better 301:306 arg1 treatment 308:316 better treatment 301:316 better treatment 301:316 It is imperative to study its tumorigenesis and development for better treatment. 37034230 8 35 theme JAK2-STAT3 1110:1119 arg1 pathway 1121:1127 the JAK2-STAT3 pathway 1106:1127 the JAK2-STAT3 pathway 1106:1127 Our study indicated that circ8199 regulates the JAK2-STAT3 pathway through OGT, providing a candidate mechanism for drug discovery and development. 37034230 1 36 theme Esophageal 122:131 arg1 tumor 189:193 an invasive malignant tumor 167:193 an invasive malignant tumor with a high incidence rate and mortality 167:234 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 1 36 theme Esophageal 122:131 arg1 ESCC 158:161 ESCC 158:161 ESCC 158:161 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 1 36 theme Esophageal 122:131 arg1 carcinoma 147:155 Esophageal squamous cell carcinoma 122:155 Esophageal squamous cell carcinoma (ESCC) 122:162 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 7 37 theme circ8199 871:878 arg1 expression 880:889 circ8199 expression 871:889 circ8199 expression 871:889 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 1 38 theme high 202:205 arg1 rate 217:220 a high incidence rate 200:220 a high incidence rate 200:220 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 0 39 theme OGT 57:59 arg1 activity 45:52 the activity 41:52 the activity of OGT 41:59 Circ8199 encodes a protein that inhibits the activity of OGT by JAK2-STAT3 pathway in esophageal squamous cell carcinoma. 37034230 4 40 theme previous 393:400 arg1 studies 402:408 Our previous studies 389:408 Our previous studies 389:408 Our previous studies found that the circ8199 gene is associated with tumor prognosis. 37034230 5 41 link O-linked 678:685 arg1 OGT 720:722 OGT 720:722 OGT 720:722 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 5 41 link O-linked 678:685 arg1 transferase 707:717 O-linked N-acetylglucosamine transferase 678:717 O-linked N-acetylglucosamine transferase (OGT) 678:723 To further clarify the role of circ8199 in ESCC, we performed functional experiments and found that overexpression of circ8199 significantly inhibited the proliferation of ESCC cells and the activity of O-linked N-acetylglucosamine transferase (OGT) simultaneously. 37034230 7 42 theme expression 880:889 arg1 reduction 858:866 The reduction 854:866 The reduction of circ8199 expression 854:889 The reduction of circ8199 expression stimulated the binding activity between OGT and its downstream gene JAK2, promoting the O-GlcNAc glycosylation modification of JAK2 and activating the JAK2-STAT3 pathway. 37034230 1 43 theme incidence 207:215 arg1 rate 217:220 a high incidence rate 200:220 a high incidence rate 200:220 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 1 44 theme cell 142:145 arg1 tumor 189:193 an invasive malignant tumor 167:193 an invasive malignant tumor with a high incidence rate and mortality 167:234 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 1 44 theme cell 142:145 arg1 ESCC 158:161 ESCC 158:161 ESCC 158:161 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 37034230 1 44 theme cell 142:145 arg1 carcinoma 147:155 Esophageal squamous cell carcinoma 122:155 Esophageal squamous cell carcinoma (ESCC) 122:162 Esophageal squamous cell carcinoma (ESCC) is an invasive malignant tumor with a high incidence rate and mortality. 35118425 3 0 theme 3D 532:533 arg1 cultures 535:542 both 2D and 3D cultures 520:542 both 2D and 3D cultures 520:542 Specifically, cellular O-GlcNAc levels are controlled through treatment of fibroblasts with inhibitors in both 2D and 3D cultures. 35118425 4 1 theme contraction 603:613 arg1 assay 615:619 3D collagen gel contraction assay 587:619 3D collagen gel contraction assay 587:619 We then describe 2D contraction assay and 3D collagen gel contraction assay to analyze the effect of the modification on sphingosine-1-phosphate signaling for contraction. 35118425 5 2 dep use 745:747 arg1 the 741:743 the 741:743 the 741:743 For complete details on the use and execution of this protocol, please refer to Pedowitz et al. (2021). 35118425 1 3 theme abundant 160:167 arg1 modification 187:198 an abundant posttranslational modification 157:198 an abundant posttranslational modification involved in a wide range of signaling pathways 157:245 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 1 3 theme abundant 160:167 arg1 β-N-acetylglucosamine 121:141 O-linked β-N-acetylglucosamine 112:141 O-linked β-N-acetylglucosamine (O-GlcNAc) 112:152 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 1 4 theme specific 256:263 arg1 role 265:268 its specific role 252:268 its specific role in regulating biological processes 252:303 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 0 5 theme fibroblast 88:97 arg1 contraction 99:109 fibroblast contraction 88:109 fibroblast contraction 88:109 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate mediated fibroblast contraction. 35118425 5 6 theme protocol 771:778 arg1 use 745:747 use 745:747 use 745:747 For complete details on the use and execution of this protocol, please refer to Pedowitz et al. (2021). 35118425 5 6 theme protocol 771:778 arg1 execution 753:761 execution 753:761 execution 753:761 For complete details on the use and execution of this protocol, please refer to Pedowitz et al. (2021). 35118425 1 7 theme O-linked 112:119 arg1 O-GlcNAc 144:151 O-GlcNAc 144:151 O-GlcNAc 144:151 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 1 7 theme O-linked 112:119 arg1 β-N-acetylglucosamine 121:141 O-linked β-N-acetylglucosamine 112:141 O-linked β-N-acetylglucosamine (O-GlcNAc) 112:152 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 1 7 theme O-linked 112:119 arg1 modification 187:198 an abundant posttranslational modification 157:198 an abundant posttranslational modification involved in a wide range of signaling pathways 157:245 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 1 8 theme posttranslational 169:185 arg1 modification 187:198 an abundant posttranslational modification 157:198 an abundant posttranslational modification involved in a wide range of signaling pathways 157:245 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 1 8 theme posttranslational 169:185 arg1 β-N-acetylglucosamine 121:141 O-linked β-N-acetylglucosamine 112:141 O-linked β-N-acetylglucosamine (O-GlcNAc) 112:152 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 0 9 theme culture 17:23 arg1 protocol 25:32 A 2D and 3D cell culture protocol 0:32 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate 0:77 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate mediated fibroblast contraction. 35118425 0 10 theme 2D 2:3 arg1 protocol 25:32 A 2D and 3D cell culture protocol 0:32 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate 0:77 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate mediated fibroblast contraction. 35118425 0 11 from protocol 25:32 arg1 sphingosine-1-phosphate 55:77 sphingosine-1-phosphate 55:77 sphingosine-1-phosphate 55:77 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate mediated fibroblast contraction. 35118425 2 12 theme fibroblast 390:399 arg1 contraction 401:411 fibroblast contraction 390:411 fibroblast contraction 390:411 This protocol describes approaches to understand O-GlcNAc's role in fibroblast contraction. 35118425 0 13 theme 3D 9:10 arg1 protocol 25:32 A 2D and 3D cell culture protocol 0:32 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate 0:77 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate mediated fibroblast contraction. 35118425 1 14 theme biological 284:293 arg1 processes 295:303 biological processes 284:303 biological processes 284:303 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 2 15 from role 382:385 arg1 contraction 401:411 fibroblast contraction 390:411 fibroblast contraction 390:411 This protocol describes approaches to understand O-GlcNAc's role in fibroblast contraction. 35118425 4 16 theme modification 650:661 arg1 effect 636:641 the effect 632:641 the effect of the modification on sphingosine-1-phosphate signaling for contraction 632:714 We then describe 2D contraction assay and 3D collagen gel contraction assay to analyze the effect of the modification on sphingosine-1-phosphate signaling for contraction. 35118425 4 17 theme collagen 590:597 arg1 assay 615:619 3D collagen gel contraction assay 587:619 3D collagen gel contraction assay 587:619 We then describe 2D contraction assay and 3D collagen gel contraction assay to analyze the effect of the modification on sphingosine-1-phosphate signaling for contraction. 35118425 1 18 theme wide 214:217 arg1 range 219:223 a wide range 212:223 a wide range of signaling pathways 212:245 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 3 19 theme O-GlcNAc 437:444 arg1 levels 446:451 cellular O-GlcNAc levels 428:451 cellular O-GlcNAc levels 428:451 Specifically, cellular O-GlcNAc levels are controlled through treatment of fibroblasts with inhibitors in both 2D and 3D cultures. 35118425 4 20 theme 3D 587:588 arg1 assay 615:619 3D collagen gel contraction assay 587:619 3D collagen gel contraction assay 587:619 We then describe 2D contraction assay and 3D collagen gel contraction assay to analyze the effect of the modification on sphingosine-1-phosphate signaling for contraction. 35118425 4 21 theme sphingosine-1-phosphate 666:688 arg1 signaling 690:698 sphingosine-1-phosphate signaling 666:698 sphingosine-1-phosphate signaling for contraction 666:714 We then describe 2D contraction assay and 3D collagen gel contraction assay to analyze the effect of the modification on sphingosine-1-phosphate signaling for contraction. 35118425 0 22 theme cell 12:15 arg1 protocol 25:32 A 2D and 3D cell culture protocol 0:32 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate 0:77 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate mediated fibroblast contraction. 35118425 4 23 theme gel 599:601 arg1 assay 615:619 3D collagen gel contraction assay 587:619 3D collagen gel contraction assay 587:619 We then describe 2D contraction assay and 3D collagen gel contraction assay to analyze the effect of the modification on sphingosine-1-phosphate signaling for contraction. 35118425 3 24 theme fibroblasts 489:499 arg1 treatment 476:484 treatment 476:484 treatment of fibroblasts with inhibitors in both 2D and 3D cultures 476:542 Specifically, cellular O-GlcNAc levels are controlled through treatment of fibroblasts with inhibitors in both 2D and 3D cultures. 35118425 4 25 from effect 636:641 arg1 signaling 690:698 sphingosine-1-phosphate signaling 666:698 sphingosine-1-phosphate signaling for contraction 666:714 We then describe 2D contraction assay and 3D collagen gel contraction assay to analyze the effect of the modification on sphingosine-1-phosphate signaling for contraction. 35118425 3 26 theme 2D 525:526 arg1 cultures 535:542 both 2D and 3D cultures 520:542 both 2D and 3D cultures 520:542 Specifically, cellular O-GlcNAc levels are controlled through treatment of fibroblasts with inhibitors in both 2D and 3D cultures. 35118425 3 27 theme cellular 428:435 arg1 levels 446:451 cellular O-GlcNAc levels 428:451 cellular O-GlcNAc levels 428:451 Specifically, cellular O-GlcNAc levels are controlled through treatment of fibroblasts with inhibitors in both 2D and 3D cultures. 35118425 4 28 theme contraction 565:575 arg1 assay 577:581 2D contraction assay 562:581 2D contraction assay 562:581 We then describe 2D contraction assay and 3D collagen gel contraction assay to analyze the effect of the modification on sphingosine-1-phosphate signaling for contraction. 35118425 5 29 theme complete 721:728 arg1 details 730:736 complete details 721:736 complete details on the use and execution of this protocol 721:778 For complete details on the use and execution of this protocol, please refer to Pedowitz et al. (2021). 35118425 4 30 theme 2D 562:563 arg1 assay 577:581 2D contraction assay 562:581 2D contraction assay 562:581 We then describe 2D contraction assay and 3D collagen gel contraction assay to analyze the effect of the modification on sphingosine-1-phosphate signaling for contraction. 35118425 1 31 link O-linked 112:119 arg1 O-GlcNAc 144:151 O-GlcNAc 144:151 O-GlcNAc 144:151 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 1 31 link O-linked 112:119 arg1 β-N-acetylglucosamine 121:141 O-linked β-N-acetylglucosamine 112:141 O-linked β-N-acetylglucosamine (O-GlcNAc) 112:152 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 1 31 link O-linked 112:119 arg1 modification 187:198 an abundant posttranslational modification 157:198 an abundant posttranslational modification involved in a wide range of signaling pathways 157:245 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 3 32 from inhibitors 506:515 arg1 cultures 535:542 both 2D and 3D cultures 520:542 both 2D and 3D cultures 520:542 Specifically, cellular O-GlcNAc levels are controlled through treatment of fibroblasts with inhibitors in both 2D and 3D cultures. 35118425 1 33 theme signaling 228:236 arg1 pathways 238:245 signaling pathways 228:245 signaling pathways 228:245 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 3 34 with treatment 476:484 arg1 inhibitors 506:515 inhibitors 506:515 inhibitors in both 2D and 3D cultures 506:542 Specifically, cellular O-GlcNAc levels are controlled through treatment of fibroblasts with inhibitors in both 2D and 3D cultures. 35118425 1 35 theme pathways 238:245 arg1 range 219:223 a wide range 212:223 a wide range of signaling pathways 212:245 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification involved in a wide range of signaling pathways, but its specific role in regulating biological processes remains unclear. 35118425 0 36 theme study 37:41 arg1 O-GlcNAc 43:50 study O-GlcNAc 37:50 study O-GlcNAc 37:50 A 2D and 3D cell culture protocol to study O-GlcNAc in sphingosine-1-phosphate mediated fibroblast contraction. 35118425 5 37 from details 730:736 arg1 use 745:747 use 745:747 use 745:747 For complete details on the use and execution of this protocol, please refer to Pedowitz et al. (2021). 35118425 5 37 from details 730:736 arg1 execution 753:761 execution 753:761 execution 753:761 For complete details on the use and execution of this protocol, please refer to Pedowitz et al. (2021). 35873990 9 0 theme proteomic 1917:1925 arg1 levels 1948:1953 proteomic and phosphoproteomic levels 1917:1953 proteomic and phosphoproteomic levels 1917:1953 We analyzed different molecular mechanisms between SPUF and GP at proteomic and phosphoproteomic levels, providing valuable information for the development and utilization of D. huoshanense. 35873990 9 1 theme molecular 1873:1881 arg1 mechanisms 1883:1892 different molecular mechanisms 1863:1892 different molecular mechanisms between SPUF and GP 1863:1912 We analyzed different molecular mechanisms between SPUF and GP at proteomic and phosphoproteomic levels, providing valuable information for the development and utilization of D. huoshanense. 35873990 6 2 theme protein 1515:1521 arg1 kinase 1523:1528 protein kinase 1515:1528 protein kinase 1515:1528 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 6 3 from enriched 1428:1435 arg1 responses 1440:1448 responses 1440:1448 responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities 1440:1562 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 5 4 located localized 1030:1038 arg1 chloroplast 1047:1057 the chloroplast 1043:1057 the chloroplast 1043:1057 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 5 4 located localized 1030:1038 arg2 DEPs 1013:1016 these DEPs 1007:1016 these DEPs 1007:1016 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 5 5 theme posttranslational 1090:1106 arg1 modification 1108:1119 posttranslational modification 1090:1119 posttranslational modification 1090:1119 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 9 6 dep development 1995:2005 arg1 the 1991:1993 the 1991:1993 the 1991:1993 We analyzed different molecular mechanisms between SPUF and GP at proteomic and phosphoproteomic levels, providing valuable information for the development and utilization of D. huoshanense. 35873990 8 7 theme D. 1801:1802 arg1 huoshanense 1804:1814 D. huoshanense 1801:1814 D. huoshanense 1801:1814 Phosphorylation characteristics and kinase categories in D. huoshanense were also clarified in this study. 35873990 5 8 theme linoleic 1242:1249 arg1 metabolism 1256:1265 linoleic acid metabolism 1242:1265 linoleic acid metabolism 1242:1265 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 3 9 from differences 662:672 arg1 mechanisms 687:696 molecular mechanisms 677:696 molecular mechanisms 677:696 Here, we conducted proteomics and phosphoproteomics analyses to reveal differences in molecular mechanisms between SPUF and GP. 35873990 6 10 located located 1389:1395 arg2 phosphoproteins 1361:1375 PLSC phosphoproteins 1356:1375 PLSC phosphoproteins 1356:1375 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 6 10 located located 1389:1395 arg1 chloroplast 1404:1414 the chloroplast 1400:1414 the chloroplast 1400:1414 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 5 11 theme cluster 976:982 arg1 analyses 984:991 cluster analyses 976:991 cluster analyses 976:991 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 9 12 theme huoshanense 2029:2039 arg1 utilization 2011:2021 utilization 2011:2021 utilization 2011:2021 We analyzed different molecular mechanisms between SPUF and GP at proteomic and phosphoproteomic levels, providing valuable information for the development and utilization of D. huoshanense. 35873990 9 12 theme huoshanense 2029:2039 arg1 development 1995:2005 development 1995:2005 development 1995:2005 We analyzed different molecular mechanisms between SPUF and GP at proteomic and phosphoproteomic levels, providing valuable information for the development and utilization of D. huoshanense. 35873990 5 13 theme acid 1251:1254 arg1 metabolism 1256:1265 linoleic acid metabolism 1242:1265 linoleic acid metabolism 1242:1265 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 6 14 from located 1389:1395 arg1 chloroplast 1404:1414 the chloroplast 1400:1414 the chloroplast 1400:1414 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 8 15 from characteristics 1760:1774 arg1 huoshanense 1804:1814 D. huoshanense 1801:1814 D. huoshanense 1801:1814 Phosphorylation characteristics and kinase categories in D. huoshanense were also clarified in this study. 35873990 8 16 theme kinase 1780:1785 arg1 categories 1787:1796 kinase categories 1780:1796 kinase categories 1780:1796 Phosphorylation characteristics and kinase categories in D. huoshanense were also clarified in this study. 35873990 1 17 theme esteemed 189:196 arg1 herb 206:209 The highly esteemed Chinese herb 178:209 The highly esteemed Chinese herb 178:209 The highly esteemed Chinese herb, Dendrobium huoshanense, whose major metabolites are polysaccharides and alkaloids, is on the verge of extinction. 35873990 1 17 theme esteemed 189:196 arg1 huoshanense 223:233 Dendrobium huoshanense 212:233 Dendrobium huoshanense 212:233 The highly esteemed Chinese herb, Dendrobium huoshanense, whose major metabolites are polysaccharides and alkaloids, is on the verge of extinction. 35873990 6 18 from chloroplast 1404:1414 arg1 located 1389:1395 located 1389:1395 located 1389:1395 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 5 19 theme carbohydrate 1122:1133 arg1 transport 1135:1143 carbohydrate transport 1122:1143 carbohydrate transport 1122:1143 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 6 20 theme different 1453:1461 arg1 stresses 1463:1470 different stresses 1453:1470 different stresses 1453:1470 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 2 21 theme different 424:432 arg1 planting 336:343 The stone planting 326:343 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense 326:414 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 21 theme different 424:432 arg1 methods 446:452 two different cultivation methods 420:452 two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy 420:588 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 1 22 theme Chinese 198:204 arg1 herb 206:209 The highly esteemed Chinese herb 178:209 The highly esteemed Chinese herb 178:209 The highly esteemed Chinese herb, Dendrobium huoshanense, whose major metabolites are polysaccharides and alkaloids, is on the verge of extinction. 35873990 1 22 theme Chinese 198:204 arg1 huoshanense 223:233 Dendrobium huoshanense 212:233 Dendrobium huoshanense 212:233 The highly esteemed Chinese herb, Dendrobium huoshanense, whose major metabolites are polysaccharides and alkaloids, is on the verge of extinction. 35873990 2 23 theme cultivation 434:444 arg1 planting 336:343 The stone planting 326:343 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense 326:414 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 23 theme cultivation 434:444 arg1 methods 446:452 two different cultivation methods 420:452 two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy 420:588 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 24 theme stone 330:334 arg1 planting 336:343 The stone planting 326:343 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense 326:414 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 24 theme stone 330:334 arg1 methods 446:452 two different cultivation methods 420:452 two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy 420:588 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 0 25 theme Comparative 0:10 arg1 Proteome 12:19 Comparative Proteome and Phosphoproteome Analyses 0:48 Proteome 12:19 Comparative Proteome and Phosphoproteome Analyses Reveal Different Molecular Mechanism Between Stone Planting Under the Forest and Greenhouse Planting of Dendrobium huoshanense. 35873990 4 26 theme phosphorylation 872:886 arg1 level 888:892 a phosphorylation level 870:892 a phosphorylation level significantly changed (PLSC) 870:921 We identified 237 differentially expressed proteins (DEPs) between the two proteomes, and 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) were observed. 35873990 4 26 theme phosphorylation 872:886 arg1 PLSC 917:920 PLSC 917:920 PLSC 917:920 We identified 237 differentially expressed proteins (DEPs) between the two proteomes, and 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) were observed. 35873990 5 27 theme protein 956:962 arg1 domain 964:969 protein domain 956:969 protein domain 956:969 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 2 28 theme greenhouse 373:382 arg1 GP 394:395 GP 394:395 GP 394:395 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 28 theme greenhouse 373:382 arg1 planting 384:391 greenhouse planting 373:391 greenhouse planting (GP) 373:396 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 0 29 theme Phosphoproteome 25:39 arg1 Analyses 41:48 Comparative Proteome and Phosphoproteome Analyses 0:48 Analyses 41:48 Comparative Proteome and Phosphoproteome Analyses Reveal Different Molecular Mechanism Between Stone Planting Under the Forest and Greenhouse Planting of Dendrobium huoshanense. 35873990 5 30 theme wax 1338:1340 arg1 biosynthesis 1342:1353 wax biosynthesis 1338:1353 wax biosynthesis 1338:1353 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 2 31 theme huoshanense 404:414 arg1 planting 336:343 The stone planting 326:343 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense 326:414 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 31 theme huoshanense 404:414 arg1 methods 446:452 two different cultivation methods 420:452 two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy 420:588 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 6 32 theme transduction 1483:1494 arg1 mechanisms 1496:1505 signal transduction mechanisms 1476:1505 signal transduction mechanisms 1476:1505 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 7 33 theme alkaloid 1712:1719 arg1 pathways 1734:1741 alkaloid biosynthesis pathways 1712:1741 alkaloid biosynthesis pathways 1712:1741 Significant differences between SPUF and GP were observed by mapping the DEPs and phosphorylated proteins to photosynthesis and polysaccharide and alkaloid biosynthesis pathways. 35873990 0 34 theme Greenhouse 131:140 arg1 Planting 142:149 Greenhouse Planting 131:149 Greenhouse Planting 131:149 Comparative Proteome and Phosphoproteome Analyses Reveal Different Molecular Mechanism Between Stone Planting Under the Forest and Greenhouse Planting of Dendrobium huoshanense. 35873990 8 35 from categories 1787:1796 arg1 huoshanense 1804:1814 D. huoshanense 1801:1814 D. huoshanense 1801:1814 Phosphorylation characteristics and kinase categories in D. huoshanense were also clarified in this study. 35873990 2 36 theme D. 401:402 arg1 huoshanense 404:414 D. huoshanense 401:414 D. huoshanense 401:414 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 37 theme Dendrobium 472:481 arg1 planting 336:343 The stone planting 326:343 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense 326:414 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 37 theme Dendrobium 472:481 arg1 methods 446:452 two different cultivation methods 420:452 two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy 420:588 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 7 38 theme biosynthesis 1721:1732 arg1 pathways 1734:1741 alkaloid biosynthesis pathways 1712:1741 alkaloid biosynthesis pathways 1712:1741 Significant differences between SPUF and GP were observed by mapping the DEPs and phosphorylated proteins to photosynthesis and polysaccharide and alkaloid biosynthesis pathways. 35873990 0 39 theme Dendrobium 154:163 arg1 huoshanense 165:175 Dendrobium huoshanense 154:175 Dendrobium huoshanense 154:175 Comparative Proteome and Phosphoproteome Analyses Reveal Different Molecular Mechanism Between Stone Planting Under the Forest and Greenhouse Planting of Dendrobium huoshanense. 35873990 3 40 theme molecular 677:685 arg1 mechanisms 687:696 molecular mechanisms 677:696 molecular mechanisms 677:696 Here, we conducted proteomics and phosphoproteomics analyses to reveal differences in molecular mechanisms between SPUF and GP. 35873990 6 41 theme PLSC 1356:1359 arg1 phosphoproteins 1361:1375 PLSC phosphoproteins 1356:1375 PLSC phosphoproteins 1356:1375 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 2 42 theme pharmaceutical 457:470 arg1 Dendrobium 472:481 pharmaceutical Dendrobium 457:481 pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy 457:588 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 1 43 theme extinction 314:323 arg1 verge 305:309 the verge 301:309 the verge of extinction 301:323 The highly esteemed Chinese herb, Dendrobium huoshanense, whose major metabolites are polysaccharides and alkaloids, is on the verge of extinction. 35873990 2 44 dep metabolites 529:539 arg1 metabolites 529:539 metabolites 529:539 metabolites content and composition 529:563 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 44 dep metabolites 529:539 arg1 composition 553:563 composition 553:563 composition 553:563 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 44 dep metabolites 529:539 arg1 content 541:547 content 541:547 content 541:547 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 3 45 theme proteomics 610:619 arg1 analyses 643:650 proteomics and phosphoproteomics analyses 610:650 proteomics and phosphoproteomics analyses 610:650 Here, we conducted proteomics and phosphoproteomics analyses to reveal differences in molecular mechanisms between SPUF and GP. 35873990 0 46 theme Molecular 67:75 arg1 Mechanism 77:85 Different Molecular Mechanism 57:85 Different Molecular Mechanism Between Stone Planting 57:108 Comparative Proteome and Phosphoproteome Analyses Reveal Different Molecular Mechanism Between Stone Planting Under the Forest and Greenhouse Planting of Dendrobium huoshanense. 35873990 5 47 theme metabolite 1175:1184 arg1 biosynthesis 1186:1197 secondary metabolite biosynthesis 1165:1197 secondary metabolite biosynthesis 1165:1197 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 2 48 from differences 502:512 arg1 efficacy 581:588 medication efficacy 570:588 medication efficacy 570:588 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 48 from differences 502:512 arg1 metabolites 529:539 metabolites 529:539 metabolites content and composition 529:563 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 48 from differences 502:512 arg1 composition 553:563 composition 553:563 composition 553:563 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 48 from differences 502:512 arg1 morphology 517:526 morphology 517:526 morphology 517:526 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 2 48 from differences 502:512 arg1 content 541:547 content 541:547 content 541:547 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 6 49 theme signal 1476:1481 arg1 mechanisms 1496:1505 signal transduction mechanisms 1476:1505 signal transduction mechanisms 1476:1505 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 0 50 theme Different 57:65 arg1 Mechanism 77:85 Different Molecular Mechanism 57:85 Different Molecular Mechanism Between Stone Planting 57:108 Comparative Proteome and Phosphoproteome Analyses Reveal Different Molecular Mechanism Between Stone Planting Under the Forest and Greenhouse Planting of Dendrobium huoshanense. 35873990 0 51 theme huoshanense 165:175 arg1 Forest 120:125 the Forest 116:125 the Forest 116:125 Comparative Proteome and Phosphoproteome Analyses Reveal Different Molecular Mechanism Between Stone Planting Under the Forest and Greenhouse Planting of Dendrobium huoshanense. 35873990 0 51 theme huoshanense 165:175 arg1 Planting 142:149 Greenhouse Planting 131:149 Greenhouse Planting 131:149 Comparative Proteome and Phosphoproteome Analyses Reveal Different Molecular Mechanism Between Stone Planting Under the Forest and Greenhouse Planting of Dendrobium huoshanense. 35873990 6 52 from responses 1440:1448 arg1 enriched 1428:1435 enriched 1428:1435 enriched 1428:1435 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 5 53 theme secondary 1165:1173 arg1 biosynthesis 1186:1197 secondary metabolite biosynthesis 1165:1197 secondary metabolite biosynthesis 1165:1197 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 9 54 theme phosphoproteomic 1931:1946 arg1 levels 1948:1953 proteomic and phosphoproteomic levels 1917:1953 proteomic and phosphoproteomic levels 1917:1953 We analyzed different molecular mechanisms between SPUF and GP at proteomic and phosphoproteomic levels, providing valuable information for the development and utilization of D. huoshanense. 35873990 4 55 theme modification 813:824 arg1 sites 826:830 291 modification sites 809:830 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) 809:921 We identified 237 differentially expressed proteins (DEPs) between the two proteomes, and 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) were observed. 35873990 9 56 theme valuable 1966:1973 arg1 information 1975:1985 valuable information 1966:1985 valuable information 1966:1985 We analyzed different molecular mechanisms between SPUF and GP at proteomic and phosphoproteomic levels, providing valuable information for the development and utilization of D. huoshanense. 35873990 5 57 theme KEGG 942:945 arg1 pathway 947:953 KEGG pathway 942:953 KEGG pathway 942:953 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 8 58 theme Phosphorylation 1744:1758 arg1 characteristics 1760:1774 Phosphorylation characteristics 1744:1774 Phosphorylation characteristics 1744:1774 Phosphorylation characteristics and kinase categories in D. huoshanense were also clarified in this study. 35873990 1 59 theme major 242:246 arg1 polysaccharides 264:278 polysaccharides 264:278 polysaccharides 264:278 The highly esteemed Chinese herb, Dendrobium huoshanense, whose major metabolites are polysaccharides and alkaloids, is on the verge of extinction. 35873990 1 59 theme major 242:246 arg1 metabolites 248:258 major metabolites 242:258 major metabolites 242:258 The highly esteemed Chinese herb, Dendrobium huoshanense, whose major metabolites are polysaccharides and alkaloids, is on the verge of extinction. 35873990 2 60 theme medication 570:579 arg1 efficacy 581:588 medication efficacy 570:588 medication efficacy 570:588 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 7 61 theme Significant 1565:1575 arg1 differences 1577:1587 Significant differences 1565:1587 Significant differences between SPUF and GP 1565:1607 Significant differences between SPUF and GP were observed by mapping the DEPs and phosphorylated proteins to photosynthesis and polysaccharide and alkaloid biosynthesis pathways. 35873990 4 62 theme expressed 752:760 arg1 DEPs 772:775 DEPs 772:775 DEPs 772:775 We identified 237 differentially expressed proteins (DEPs) between the two proteomes, and 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) were observed. 35873990 4 62 theme expressed 752:760 arg1 proteins 762:769 237 differentially expressed proteins 733:769 237 differentially expressed proteins (DEPs) between the two proteomes 733:802 We identified 237 differentially expressed proteins (DEPs) between the two proteomes, and 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) were observed. 35873990 6 63 theme phosphotransferase 1534:1551 arg1 activities 1553:1562 phosphotransferase activities 1534:1562 phosphotransferase activities 1534:1562 PLSC phosphoproteins were mainly located in the chloroplast, and highly enriched in responses to different stresses and signal transduction mechanisms through protein kinase and phosphotransferase activities. 35873990 9 64 theme D. 2026:2027 arg1 huoshanense 2029:2039 D. huoshanense 2026:2039 D. huoshanense 2026:2039 We analyzed different molecular mechanisms between SPUF and GP at proteomic and phosphoproteomic levels, providing valuable information for the development and utilization of D. huoshanense. 35873990 9 65 theme different 1863:1871 arg1 mechanisms 1883:1892 different molecular mechanisms 1863:1892 different molecular mechanisms between SPUF and GP 1863:1912 We analyzed different molecular mechanisms between SPUF and GP at proteomic and phosphoproteomic levels, providing valuable information for the development and utilization of D. huoshanense. 35873990 1 66 theme Dendrobium 212:221 arg1 herb 206:209 The highly esteemed Chinese herb 178:209 The highly esteemed Chinese herb 178:209 The highly esteemed Chinese herb, Dendrobium huoshanense, whose major metabolites are polysaccharides and alkaloids, is on the verge of extinction. 35873990 1 66 theme Dendrobium 212:221 arg1 huoshanense 223:233 Dendrobium huoshanense 212:233 Dendrobium huoshanense 212:233 The highly esteemed Chinese herb, Dendrobium huoshanense, whose major metabolites are polysaccharides and alkaloids, is on the verge of extinction. 35873990 5 67 theme plant-pathogen 1268:1281 arg1 interactions 1283:1294 plant-pathogen interactions 1268:1294 plant-pathogen interactions 1268:1294 GO, KEGG pathway, protein domain, and cluster analyses revealed that these DEPs were mainly localized in the chloroplast; involved in processes such as posttranslational modification, carbohydrate transport and metabolism, and secondary metabolite biosynthesis; and enriched in pathways mainly including linoleic acid metabolism, plant-pathogen interactions, and phenylpropanoid, cutin, suberin, and wax biosynthesis. 35873990 4 68 dep changed 908:914 arg1 level 888:892 a phosphorylation level 870:892 a phosphorylation level significantly changed (PLSC) 870:921 We identified 237 differentially expressed proteins (DEPs) between the two proteomes, and 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) were observed. 35873990 4 68 dep changed 908:914 arg1 PLSC 917:920 PLSC 917:920 PLSC 917:920 We identified 237 differentially expressed proteins (DEPs) between the two proteomes, and 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) were observed. 35873990 3 69 theme phosphoproteomics 625:641 arg1 analyses 643:650 proteomics and phosphoproteomics analyses 610:650 proteomics and phosphoproteomics analyses 610:650 Here, we conducted proteomics and phosphoproteomics analyses to reveal differences in molecular mechanisms between SPUF and GP. 35873990 2 70 with Dendrobium 472:481 arg1 differences 502:512 significantly differences 488:512 significantly differences in morphology, metabolites content and composition, and medication efficacy 488:588 The stone planting under the forest (SPUF) and greenhouse planting (GP) of D. huoshanense are two different cultivation methods of pharmaceutical Dendrobium with significantly differences in morphology, metabolites content and composition, and medication efficacy. 35873990 4 71 with phosphoproteins 849:863 arg1 level 888:892 a phosphorylation level 870:892 a phosphorylation level significantly changed (PLSC) 870:921 We identified 237 differentially expressed proteins (DEPs) between the two proteomes, and 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) were observed. 35873990 4 71 with phosphoproteins 849:863 arg1 PLSC 917:920 PLSC 917:920 PLSC 917:920 We identified 237 differentially expressed proteins (DEPs) between the two proteomes, and 291 modification sites belonging to 215 phosphoproteins with a phosphorylation level significantly changed (PLSC) were observed. 35873990 7 72 theme phosphorylated 1647:1660 arg1 proteins 1662:1669 phosphorylated proteins 1647:1669 phosphorylated proteins 1647:1669 Significant differences between SPUF and GP were observed by mapping the DEPs and phosphorylated proteins to photosynthesis and polysaccharide and alkaloid biosynthesis pathways. 37316064 7 0 theme rubbery 1160:1166 arg1 notes 1168:1172 rubbery notes 1160:1172 rubbery notes 1160:1172 After drying and roasting, the coffee soaked with SCG enzymatic extract displayed lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile as compared to untreated reference. 37316064 9 1 theme novel 1570:1574 arg1 technology 1576:1585 This novel technology 1565:1585 This novel technology 1565:1585 This novel technology could represent an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup. 37316064 6 2 dep glucose 898:904 arg1 % 919:919 8.41 ± 1.00 % 907:919 8.41 ± 1.00 % of total SCG mass 907:937 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 6 2 dep glucose 898:904 arg1 mass 934:937 total SCG mass 924:937 total SCG mass 924:937 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 1 3 theme instant 246:252 arg1 production 261:270 instant coffee production 246:270 instant coffee production 246:270 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 5 4 theme enzymes 790:796 arg1 combination 746:756 a combination 744:756 a combination of specific carbohydrate active enzymes 744:796 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 1 5 theme Spent 163:167 arg1 SCG 185:187 SCG 185:187 SCG 185:187 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 1 5 theme Spent 163:167 arg1 by-products 194:204 by-products 194:204 by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption 194:339 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 1 5 theme Spent 163:167 arg1 grounds 176:182 Spent coffee grounds 163:182 Spent coffee grounds (SCG) 163:188 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 6 6 theme generated 846:854 arg1 extract 867:873 The generated sugar-rich extract 842:873 The generated sugar-rich extract 842:873 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 0 7 with bean 88:91 arg1 grounds 133:139 enzymatically treated spent coffee grounds 98:139 enzymatically treated spent coffee grounds 98:139 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 6 8 theme mass 934:937 arg1 % 919:919 8.41 ± 1.00 % 907:919 8.41 ± 1.00 % of total SCG mass 907:937 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 6 8 theme mass 934:937 arg1 mass 934:937 total SCG mass 924:937 total SCG mass 924:937 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 9 9 theme in 1617:1618 arg1 stream 1638:1643 an innovative in situ valorization stream 1603:1643 an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup 1603:1718 This novel technology could represent an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup. 37316064 4 10 theme cellulose 615:623 arg1 polysaccharides 640:654 cellulose, hemicellulose polysaccharides 615:654 cellulose, hemicellulose polysaccharides 615:654 However, this by-product is mainly composed of cellulose, hemicellulose polysaccharides and lipids. 37316064 8 11 from reduction 1518:1526 arg1 compounds 1540:1548 phenolic compounds 1531:1548 phenolic compounds 1531:1548 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 8 11 from reduction 1518:1526 arg1 generation 1379:1388 the generation 1375:1388 the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting 1375:1483 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 8 11 from reduction 1518:1526 arg1 pyrazines 1554:1562 pyrazines 1554:1562 pyrazines 1554:1562 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 5 12 theme extraction 814:823 arg1 yield 825:829 sugar extraction yield 808:829 sugar extraction yield of 74.3 % 808:839 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 6 13 theme total 924:928 arg1 mass 934:937 total SCG mass 924:937 total SCG mass 924:937 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 9 14 theme valorization 1625:1636 arg1 stream 1638:1643 an innovative in situ valorization stream 1603:1643 an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup 1603:1718 This novel technology could represent an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup. 37316064 8 15 theme 2-fold 1356:1361 arg1 increase 1363:1370 a 2-fold increase 1354:1370 a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting 1354:1483 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 0 16 theme coffee 126:131 arg1 grounds 133:139 enzymatically treated spent coffee grounds 98:139 enzymatically treated spent coffee grounds 98:139 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 6 17 theme green 1040:1044 arg1 coffee 1046:1051 green coffee 1040:1051 green coffee 1040:1051 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 9 18 theme coffee 1653:1658 arg1 industry 1660:1667 the coffee industry 1649:1667 the coffee industry 1649:1667 This novel technology could represent an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup. 37316064 0 19 theme circular 144:151 arg1 approach 153:160 A circular approach 142:160 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 0:161 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 6 20 theme total 970:974 arg1 mass 980:983 total SCG mass 970:983 total SCG mass 970:983 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 8 21 theme sugar-derived 1393:1405 arg1 diketones 1448:1456 diketones 1448:1456 diketones 1448:1456 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 8 21 theme sugar-derived 1393:1405 arg1 aldehydes 1434:1442 Strecker aldehydes 1425:1442 Strecker aldehydes 1425:1442 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 8 21 theme sugar-derived 1393:1405 arg1 molecules 1407:1415 sugar-derived molecules 1393:1415 sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting 1393:1483 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 8 22 theme Strecker 1425:1432 arg1 aldehydes 1434:1442 Strecker aldehydes 1425:1442 Strecker aldehydes 1425:1442 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 0 23 theme coffee 81:86 arg1 bean 88:91 the green coffee bean 71:91 the green coffee bean with enzymatically treated spent coffee grounds 71:139 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 1 24 theme consumption 329:339 arg1 point 320:324 the point 316:324 the point of consumption 316:339 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 8 25 dep % 1516:1516 arg1 37 1513:1514 37 1513:1514 37 1513:1514 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 6 26 theme hydrolyzed 1005:1014 arg1 grounds 1016:1022 hydrolyzed grounds 1005:1022 hydrolyzed grounds 1005:1022 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 9 27 theme cup 1716:1718 arg1 improvement 1691:1701 sensory improvement 1683:1701 sensory improvement of the final cup 1683:1718 This novel technology could represent an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup. 37316064 7 28 theme SCG 1104:1106 arg1 extract 1118:1124 SCG enzymatic extract 1104:1124 SCG enzymatic extract 1104:1124 After drying and roasting, the coffee soaked with SCG enzymatic extract displayed lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile as compared to untreated reference. 37316064 1 29 theme coffee 254:259 arg1 production 261:270 instant coffee production 246:270 instant coffee production 246:270 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 2 30 theme materials 397:405 arg1 worldwide 407:415 the largest waste materials worldwide 379:415 the largest waste materials worldwide 379:415 This solid residue represents one of the largest waste materials worldwide, making this fraction a rational target for valorization. 37316064 0 31 theme Robusta 15:21 arg1 aroma 30:34 Robusta coffee aroma 15:34 Robusta coffee aroma 15:34 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 9 32 dep in 1617:1618 arg1 situ 1620:1623 situ 1620:1623 situ 1620:1623 This novel technology could represent an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup. 37316064 3 33 dep varies 498:503 arg1 depending 519:527 depending 519:527 varies significantly depending on the brewing and extraction methods 498:565 The composition of SCG varies significantly depending on the brewing and extraction methods. 37316064 8 34 link sugar-derived 1393:1405 arg1 diketones 1448:1456 diketones 1448:1456 diketones 1448:1456 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 8 34 link sugar-derived 1393:1405 arg1 aldehydes 1434:1442 Strecker aldehydes 1425:1442 Strecker aldehydes 1425:1442 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 8 34 link sugar-derived 1393:1405 arg1 molecules 1407:1415 sugar-derived molecules 1393:1415 sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting 1393:1483 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 2 35 theme largest 383:389 arg1 worldwide 407:415 the largest waste materials worldwide 379:415 the largest waste materials worldwide 379:415 This solid residue represents one of the largest waste materials worldwide, making this fraction a rational target for valorization. 37316064 0 36 theme aroma 30:34 arg1 Improvement 0:10 Improvement 0:10 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 0:161 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 6 37 theme mass 980:983 arg1 mass 980:983 total SCG mass 970:983 total SCG mass 970:983 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 6 37 theme mass 980:983 arg1 % 965:965 2.88 ± 0.25 % 953:965 2.88 ± 0.25 % of total SCG mass 953:983 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 8 38 theme 45 1491:1492 arg1 % 1494:1494 % 1494:1494 % 1494:1494 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 8 39 theme sensorial 1331:1339 arg1 effect 1341:1346 the sensorial effect 1327:1346 the sensorial effect 1327:1346 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 5 40 theme carbohydrate 770:781 arg1 enzymes 790:796 specific carbohydrate active enzymes 761:796 specific carbohydrate active enzymes 761:796 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 7 41 theme smoother 1185:1192 arg1 notes 1210:1214 smoother and more acidic notes 1185:1214 lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile 1136:1236 After drying and roasting, the coffee soaked with SCG enzymatic extract displayed lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile as compared to untreated reference. 37316064 3 42 theme SCG 494:496 arg1 composition 479:489 The composition 475:489 The composition of SCG 475:496 The composition of SCG varies significantly depending on the brewing and extraction methods. 37316064 5 43 theme % 839:839 arg1 yield 825:829 sugar extraction yield 808:829 sugar extraction yield of 74.3 % 808:839 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 5 44 theme specific 761:768 arg1 enzymes 790:796 specific carbohydrate active enzymes 761:796 specific carbohydrate active enzymes 761:796 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 0 45 dep Improvement 0:10 arg1 approach 153:160 A circular approach 142:160 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 0:161 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 8 46 from increase 1363:1370 arg1 compounds 1540:1548 phenolic compounds 1531:1548 phenolic compounds 1531:1548 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 8 46 from increase 1363:1370 arg1 generation 1379:1388 the generation 1375:1388 the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting 1375:1483 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 8 46 from increase 1363:1370 arg1 pyrazines 1554:1562 pyrazines 1554:1562 pyrazines 1554:1562 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 1 47 theme industrial 224:233 arg1 process 235:241 the industrial process 220:241 the industrial process of instant coffee production 220:270 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 8 48 theme phenolic 1531:1538 arg1 compounds 1540:1548 phenolic compounds 1531:1548 phenolic compounds 1531:1548 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 6 49 theme sugar-rich 856:865 arg1 extract 867:873 The generated sugar-rich extract 842:873 The generated sugar-rich extract 842:873 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 3 50 theme extraction 548:557 arg1 methods 559:565 the brewing and extraction methods 532:565 methods 559:565 The composition of SCG varies significantly depending on the brewing and extraction methods. 37316064 1 51 theme coffee 169:174 arg1 SCG 185:187 SCG 185:187 SCG 185:187 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 1 51 theme coffee 169:174 arg1 by-products 194:204 by-products 194:204 by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption 194:339 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 1 51 theme coffee 169:174 arg1 grounds 176:182 Spent coffee grounds 163:182 Spent coffee grounds (SCG) 163:188 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 9 52 theme innovative 1606:1615 arg1 stream 1638:1643 an innovative in situ valorization stream 1603:1643 an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup 1603:1718 This novel technology could represent an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup. 37316064 0 53 theme spent 120:124 arg1 grounds 133:139 enzymatically treated spent coffee grounds 98:139 enzymatically treated spent coffee grounds 98:139 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 3 54 theme brewing 536:542 arg1 methods 559:565 the brewing and extraction methods 532:565 methods 559:565 The composition of SCG varies significantly depending on the brewing and extraction methods. 37316064 5 55 theme sugar 808:812 arg1 yield 825:829 sugar extraction yield 808:829 sugar extraction yield of 74.3 % 808:839 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 6 56 theme SCG 930:932 arg1 mass 934:937 total SCG mass 924:937 total SCG mass 924:937 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 2 57 theme solid 347:351 arg1 residue 353:359 This solid residue 342:359 This solid residue 342:359 This solid residue represents one of the largest waste materials worldwide, making this fraction a rational target for valorization. 37316064 5 58 theme enzymatic 691:699 arg1 hydrolysis 701:710 the enzymatic hydrolysis 687:710 the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes 687:796 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 6 59 theme SCG 976:978 arg1 mass 980:983 total SCG mass 970:983 total SCG mass 970:983 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 8 60 theme molecules 1407:1415 arg1 generation 1379:1388 the generation 1375:1388 the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting 1375:1483 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 6 61 dep mannose 944:950 arg1 mass 980:983 total SCG mass 970:983 total SCG mass 970:983 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 6 61 dep mannose 944:950 arg1 % 965:965 2.88 ± 0.25 % 953:965 2.88 ± 0.25 % of total SCG mass 953:983 The generated sugar-rich extract, primarily composed of glucose (8.41 ± 1.00 % of total SCG mass) and mannose (2.88 ± 0.25 % of total SCG mass), is separated from hydrolyzed grounds and soaked with green coffee. 37316064 7 62 theme untreated 1253:1261 arg1 reference 1263:1271 untreated reference 1253:1271 untreated reference 1253:1271 After drying and roasting, the coffee soaked with SCG enzymatic extract displayed lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile as compared to untreated reference. 37316064 5 63 theme industrial 715:724 arg1 SCG 726:728 industrial SCG 715:728 industrial SCG 715:728 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 0 64 theme green 75:79 arg1 bean 88:91 the green coffee bean 71:91 the green coffee bean with enzymatically treated spent coffee grounds 71:139 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 9 65 theme sensory 1683:1689 arg1 improvement 1691:1701 sensory improvement 1683:1701 sensory improvement of the final cup 1683:1718 This novel technology could represent an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup. 37316064 5 66 theme SCG 726:728 arg1 hydrolysis 701:710 the enzymatic hydrolysis 687:710 the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes 687:796 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 9 67 theme final 1710:1714 arg1 cup 1716:1718 the final cup 1706:1718 the final cup 1706:1718 This novel technology could represent an innovative in situ valorization stream for the coffee industry, coupled with sensory improvement of the final cup. 37316064 7 68 theme enzymatic 1108:1116 arg1 extract 1118:1124 SCG enzymatic extract 1104:1124 SCG enzymatic extract 1104:1124 After drying and roasting, the coffee soaked with SCG enzymatic extract displayed lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile as compared to untreated reference. 37316064 5 69 theme active 783:788 arg1 enzymes 790:796 specific carbohydrate active enzymes 761:796 specific carbohydrate active enzymes 761:796 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 7 70 theme flavor 1223:1228 arg1 profile 1230:1236 the flavor profile 1219:1236 the flavor profile 1219:1236 After drying and roasting, the coffee soaked with SCG enzymatic extract displayed lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile as compared to untreated reference. 37316064 8 71 theme Aroma 1274:1278 arg1 profiling 1280:1288 Aroma profiling 1274:1288 Aroma profiling performed by SPME-GC-MS 1274:1312 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 0 72 theme coffee 23:28 arg1 aroma 30:34 Robusta coffee aroma 15:34 Robusta coffee aroma 15:34 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 1 73 theme production 261:270 arg1 process 235:241 the industrial process 220:241 the industrial process of instant coffee production 220:270 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 2 74 theme worldwide 407:415 arg1 one 372:374 one 372:374 one 372:374 This solid residue represents one of the largest waste materials worldwide, making this fraction a rational target for valorization. 37316064 2 74 theme worldwide 407:415 arg1 worldwide 407:415 the largest waste materials worldwide 379:415 the largest waste materials worldwide 379:415 This solid residue represents one of the largest waste materials worldwide, making this fraction a rational target for valorization. 37316064 2 75 theme waste 391:395 arg1 worldwide 407:415 the largest waste materials worldwide 379:415 the largest waste materials worldwide 379:415 This solid residue represents one of the largest waste materials worldwide, making this fraction a rational target for valorization. 37316064 5 76 theme combination 746:756 arg1 use 737:739 the use 733:739 the use of a combination of specific carbohydrate active enzymes 733:796 Here, we report on the enzymatic hydrolysis of industrial SCG by the use of a combination of specific carbohydrate active enzymes, enabling sugar extraction yield of 74.3 %. 37316064 7 77 theme acidic 1203:1208 arg1 notes 1210:1214 smoother and more acidic notes 1185:1214 lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile 1136:1236 After drying and roasting, the coffee soaked with SCG enzymatic extract displayed lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile as compared to untreated reference. 37316064 2 78 theme rational 441:448 arg1 target 450:455 a rational target 439:455 a rational target for valorization 439:472 This solid residue represents one of the largest waste materials worldwide, making this fraction a rational target for valorization. 37316064 8 79 theme % 1494:1494 arg1 reduction 1518:1526 a 45 % and respectively 37 % reduction 1489:1526 a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines 1489:1562 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 0 80 theme flavor 50:55 arg1 precursors 57:66 flavor precursors 50:66 flavor precursors 50:66 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37316064 4 81 dep cellulose 615:623 arg1 hemicellulose 626:638 hemicellulose 626:638 hemicellulose 626:638 However, this by-product is mainly composed of cellulose, hemicellulose polysaccharides and lipids. 37316064 7 82 from notes 1210:1214 arg1 profile 1230:1236 the flavor profile 1219:1236 the flavor profile 1219:1236 After drying and roasting, the coffee soaked with SCG enzymatic extract displayed lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile as compared to untreated reference. 37316064 1 83 theme coffee 306:311 arg1 brewing 295:301 brewing 295:301 brewing of coffee 295:311 Spent coffee grounds (SCG) are by-products obtained from the industrial process of instant coffee production or alternatively after brewing of coffee at the point of consumption. 37316064 8 84 theme % 1516:1516 arg1 reduction 1518:1526 a 45 % and respectively 37 % reduction 1489:1526 a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines 1489:1562 Aroma profiling performed by SPME-GC-MS corroborated the sensorial effect, with a 2-fold increase in the generation of sugar-derived molecules such as Strecker aldehydes and diketones after soaking and roasting and a 45 % and respectively 37 % reduction in phenolic compounds and pyrazines. 37316064 7 85 dep lower 1136:1140 arg1 earthy 1142:1147 earthy 1142:1147 earthy 1142:1147 After drying and roasting, the coffee soaked with SCG enzymatic extract displayed lower earthy, burnt and rubbery notes as well as smoother and more acidic notes in the flavor profile as compared to untreated reference. 37316064 0 86 theme treated 112:118 arg1 grounds 133:139 enzymatically treated spent coffee grounds 98:139 enzymatically treated spent coffee grounds 98:139 Improvement of Robusta coffee aroma by modulating flavor precursors in the green coffee bean with enzymatically treated spent coffee grounds: A circular approach. 37259412 8 0 theme immunocytochemical 1052:1069 arg1 staining 1071:1078 immunocytochemical staining 1052:1078 immunocytochemical staining 1052:1078 Moreover, the collagen type III expression was examined using immunocytochemical staining. 37259412 19 1 from use 2214:2216 arg1 form-decoction 2264:2277 its traditional, safe form-decoction 2242:2277 its traditional, safe form-decoction 2242:2277 The results obtained encourage the use of this raw material in its traditional, safe form-decoction. 37259412 15 2 theme gingival 1787:1794 arg1 fibroblasts 1796:1806 human gingival fibroblasts 1781:1806 human gingival fibroblasts 1781:1806 It significantly stimulated human gingival fibroblasts to proliferate, migrate, and increase the synthesis of collagen III. 37259412 3 3 theme raw 196:198 arg1 material 200:207 a pharmacopoeial raw material 179:207 a pharmacopoeial raw material in Europe and China 179:227 is a pharmacopoeial raw material in Europe and China. 37259412 19 4 dep traditional 2246:2256 arg1 safe 2259:2262 safe 2259:2262 safe 2259:2262 The results obtained encourage the use of this raw material in its traditional, safe form-decoction. 37259412 6 5 dep in 704:705 arg1 vitro 707:711 vitro 707:711 vitro 707:711 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 5 6 theme oral 457:460 arg1 wounds 466:471 oral gum wounds 457:471 oral gum wounds 457:471 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 7 7 used used 764:767 arg2 We 761:762 We 761:762 We 761:762 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 17 8 theme high 2026:2029 arg1 levels 2031:2036 high levels 2026:2036 high levels of polysaccharides 2026:2055 In contrast, high levels of polysaccharides were observed. 37259412 6 9 theme wound 722:726 arg1 healing 728:734 its in vitro gingival wound healing 700:734 its in vitro gingival wound healing activity 700:743 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 7 10 theme primary 773:779 arg1 fibroblasts 796:806 the primary human gingival fibroblasts 769:806 the primary human gingival fibroblasts (HGF) incubated with a decoction 769:839 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 10 theme primary 773:779 arg1 HGF 809:811 HGF 809:811 HGF 809:811 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 9 11 theme validated 1164:1172 arg1 method 1198:1203 the validated HPLC/DAD/ESI-HR-QTOF-MS method 1160:1203 the validated HPLC/DAD/ESI-HR-QTOF-MS method 1160:1203 The studied decoction was qualitatively and quantitatively characterized using the validated HPLC/DAD/ESI-HR-QTOF-MS method. 37259412 10 12 theme tannins 1276:1282 arg1 content 1284:1290 the total phenols and tannins content 1254:1290 the total phenols and tannins content 1254:1290 The Folin-Ciocalteu assay was used to determine the total phenols and tannins content. 37259412 12 13 theme cell 1562:1565 arg1 viability 1567:1575 HGF cell viability 1558:1575 HGF cell viability 1558:1575 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. 37259412 11 14 used used 1398:1401 arg2 analysis 1315:1322 HPLC-RI analysis 1307:1322 HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts 1307:1392 Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. 37259412 6 15 theme medicines 521:529 arg1 decoctions 577:586 water decoctions 571:586 water decoctions 571:586 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 6 15 theme medicines 521:529 arg1 majority 502:509 a majority 500:509 a majority of herbal medicines 500:529 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 7 16 theme healing 974:980 arg1 migration 957:965 cell migration 952:965 cell migration (wound healing assay) 952:987 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 16 theme healing 974:980 arg1 assay 982:986 wound healing assay 968:986 wound healing assay 968:986 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 18 17 theme wound 2135:2139 arg1 healing 2141:2147 oral wound healing 2130:2147 the oral wound healing parameters analyzed in vitro 2126:2176 In our opinion, they may have a significant effect on the oral wound healing parameters analyzed in vitro. 37259412 4 18 from healing 321:327 arg1 medicine 245:252 traditional medicine 233:252 traditional medicine 233:252 In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. 37259412 7 19 theme scanning 921:928 arg1 microscope-CLSM 930:944 the confocal laser scanning microscope-CLSM 902:944 the confocal laser scanning microscope-CLSM 902:944 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 19 theme scanning 921:928 arg1 proliferation 887:899 cell proliferation 882:899 cell proliferation (the confocal laser scanning microscope-CLSM) 882:945 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 12 20 theme significant 1534:1544 arg1 increase 1546:1553 a significant increase 1532:1553 a significant increase in HGF cell viability 1532:1575 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. 37259412 7 21 theme cell 952:955 arg1 migration 957:965 cell migration 952:965 cell migration (wound healing assay) 952:987 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 21 theme cell 952:955 arg1 assay 982:986 wound healing assay 968:986 wound healing assay 968:986 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 17 22 located observed 2062:2069 arg1 contrast 2016:2023 contrast 2016:2023 contrast 2016:2023 In contrast, high levels of polysaccharides were observed. 37259412 17 22 located observed 2062:2069 arg2 levels 2031:2036 high levels 2026:2036 high levels of polysaccharides 2026:2055 In contrast, high levels of polysaccharides were observed. 37259412 7 23 theme confocal 906:913 arg1 microscope-CLSM 930:944 the confocal laser scanning microscope-CLSM 902:944 the confocal laser scanning microscope-CLSM 902:944 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 23 theme confocal 906:913 arg1 proliferation 887:899 cell proliferation 882:899 cell proliferation (the confocal laser scanning microscope-CLSM) 882:945 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 6 24 theme herbal 514:519 arg1 medicines 521:529 herbal medicines 514:529 herbal medicines 514:529 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 12 25 theme h 1512:1512 arg1 incubation 1514:1523 24 h incubation 1509:1523 24 h incubation 1509:1523 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. 37259412 12 26 dep 1000 1478:1481 arg1 to 1475:1476 to 1475:1476 to 1475:1476 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. 37259412 0 27 theme Decoction-In 68:79 arg1 Study 87:91 Decoction-In Vitro Study 68:91 Decoction-In Vitro Study 68:91 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix Decoction-In Vitro Study. 37259412 7 28 theme cell 882:885 arg1 microscope-CLSM 930:944 the confocal laser scanning microscope-CLSM 902:944 the confocal laser scanning microscope-CLSM 902:944 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 28 theme cell 882:885 arg1 proliferation 887:899 cell proliferation 882:899 cell proliferation (the confocal laser scanning microscope-CLSM) 882:945 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 5 29 theme recent 335:340 arg1 study 351:355 a recent in vitro study 333:355 a recent in vitro study 333:355 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 6 30 theme water 571:575 arg1 decoctions 577:586 water decoctions 571:586 water decoctions 571:586 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 6 30 theme water 571:575 arg1 majority 502:509 a majority 500:509 a majority of herbal medicines 500:529 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 16 31 theme fewer 1921:1925 arg1 polyphenols 1927:1937 significantly fewer polyphenols 1907:1937 significantly fewer polyphenols in the decoction 1907:1954 Phytochemical analysis showed significantly fewer polyphenols in the decoction than in the ethanol and acetone extracts tested earlier. 37259412 13 32 theme tested 1618:1623 arg1 µg/mL 1651:1655 up to 2000 µg/mL 1640:1655 up to 2000 µg/mL 1640:1655 No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). 37259412 13 32 theme tested 1618:1623 arg1 concentration 1625:1637 any tested concentration 1614:1637 any tested concentration (up to 2000 µg/mL) 1614:1656 No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). 37259412 1 33 dep Rhizoma 113:119 arg1 Radix 124:128 Polygoni Cuspidati Rhizoma et Radix 94:128 Polygoni Cuspidati Rhizoma et Radix (syn. 94:134 Polygoni Cuspidati Rhizoma et Radix (syn. 37259412 1 33 dep Rhizoma 113:119 arg1 syn 131:133 syn 131:133 syn 131:133 Polygoni Cuspidati Rhizoma et Radix (syn. 37259412 16 34 from polyphenols 1927:1937 arg1 decoction 1946:1954 the decoction 1942:1954 the decoction 1942:1954 Phytochemical analysis showed significantly fewer polyphenols in the decoction than in the ethanol and acetone extracts tested earlier. 37259412 7 35 theme MTT 870:872 arg1 viability 859:867 cell viability 854:867 cell viability (MTT assay) 854:879 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 35 theme MTT 870:872 arg1 assay 874:878 MTT assay 870:878 MTT assay 870:878 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 0 36 dep Study 87:91 arg1 Potential 19:27 Oral Wound Healing Potential 0:27 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix 0:66 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix Decoction-In Vitro Study. 37259412 3 37 theme pharmacopoeial 181:194 arg1 material 200:207 a pharmacopoeial raw material 179:207 a pharmacopoeial raw material in Europe and China 179:227 is a pharmacopoeial raw material in Europe and China. 37259412 6 38 theme japonica 637:644 arg1 rhizomes 646:653 Reynoutria japonica rhizomes 626:653 Reynoutria japonica rhizomes 626:653 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 0 39 theme Oral 0:3 arg1 Healing 11:17 Oral Wound Healing 0:17 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix 0:66 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix Decoction-In Vitro Study. 37259412 12 40 from µg/mL 1483:1487 arg1 concentration 1452:1464 Low concentration 1448:1464 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation 1448:1523 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. 37259412 0 41 dep Decoction-In 68:79 arg1 Vitro 81:85 Vitro 81:85 Vitro 81:85 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix Decoction-In Vitro Study. 37259412 5 42 contain have 430:433 arg2 potential 439:447 the potential to heal oral gum wounds 435:471 the potential to heal oral gum wounds 435:471 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 5 42 contain have 430:433 arg1 extracts 399:406 ethanol and acetone extracts 379:406 ethanol and acetone extracts from this herbal drug 379:428 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 11 43 theme saccharides 1435:1445 arg1 composition 1420:1430 the composition 1416:1430 the composition of saccharides 1416:1445 Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. 37259412 0 44 theme Healing 11:17 arg1 Potential 19:27 Oral Wound Healing Potential 0:27 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix 0:66 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix Decoction-In Vitro Study. 37259412 2 45 theme Houtt 168:172 arg1 rhizomes 136:143 rhizomes 136:143 rhizomes of Reynoutria japonica Houtt. 136:173 rhizomes of Reynoutria japonica Houtt.) 37259412 10 46 theme total 1258:1262 arg1 content 1284:1290 the total phenols and tannins content 1254:1290 the total phenols and tannins content 1254:1290 The Folin-Ciocalteu assay was used to determine the total phenols and tannins content. 37259412 14 47 dep active 1670:1675 arg1 lowest 1663:1668 lowest 1663:1668 lowest 1663:1668 The lowest active concentration of decoction (50 µg/mL) was selected for further experiments. 37259412 2 48 theme Reynoutria 148:157 arg1 Houtt 168:172 Reynoutria japonica Houtt 148:172 Reynoutria japonica Houtt 148:172 rhizomes of Reynoutria japonica Houtt.) 37259412 6 49 theme in 704:705 arg1 healing 728:734 its in vitro gingival wound healing 700:734 its in vitro gingival wound healing activity 700:743 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 16 50 theme acetone 1980:1986 arg1 extracts 1988:1995 the ethanol and acetone extracts 1964:1995 the ethanol and acetone extracts tested earlier 1964:2010 Phytochemical analysis showed significantly fewer polyphenols in the decoction than in the ethanol and acetone extracts tested earlier. 37259412 8 51 theme collagen 1004:1011 arg1 expression 1022:1031 the collagen type III expression 1000:1031 the collagen type III expression 1000:1031 Moreover, the collagen type III expression was examined using immunocytochemical staining. 37259412 12 52 theme Low 1448:1450 arg1 concentration 1452:1464 Low concentration 1448:1464 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation 1448:1523 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. 37259412 13 53 theme cytotoxic 1581:1589 arg1 effect 1591:1596 No cytotoxic effect 1578:1596 No cytotoxic effect 1578:1596 No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). 37259412 7 54 theme cell 854:857 arg1 viability 859:867 cell viability 854:867 cell viability (MTT assay) 854:879 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 54 theme cell 854:857 arg1 assay 874:878 MTT assay 870:878 MTT assay 870:878 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 16 55 theme Phytochemical 1877:1889 arg1 analysis 1891:1898 Phytochemical analysis 1877:1898 Phytochemical analysis 1877:1898 Phytochemical analysis showed significantly fewer polyphenols in the decoction than in the ethanol and acetone extracts tested earlier. 37259412 4 56 theme japonica 294:301 arg1 rhizomes 303:310 Reynoutria japonica rhizomes 283:310 Reynoutria japonica rhizomes 283:310 In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. 37259412 7 57 theme gingival 787:794 arg1 fibroblasts 796:806 the primary human gingival fibroblasts 769:806 the primary human gingival fibroblasts (HGF) incubated with a decoction 769:839 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 57 theme gingival 787:794 arg1 HGF 809:811 HGF 809:811 HGF 809:811 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 5 58 theme herbal 418:423 arg1 drug 425:428 this herbal drug 413:428 this herbal drug 413:428 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 15 59 theme human 1781:1785 arg1 fibroblasts 1796:1806 human gingival fibroblasts 1781:1806 human gingival fibroblasts 1781:1806 It significantly stimulated human gingival fibroblasts to proliferate, migrate, and increase the synthesis of collagen III. 37259412 9 60 theme studied 1085:1091 arg1 decoction 1093:1101 The studied decoction 1081:1101 The studied decoction 1081:1101 The studied decoction was qualitatively and quantitatively characterized using the validated HPLC/DAD/ESI-HR-QTOF-MS method. 37259412 5 61 theme ethanol 379:385 arg1 extracts 399:406 ethanol and acetone extracts 379:406 ethanol and acetone extracts from this herbal drug 379:428 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 14 62 theme active 1670:1675 arg1 µg/mL 1708:1712 50 µg/mL 1705:1712 50 µg/mL 1705:1712 The lowest active concentration of decoction (50 µg/mL) was selected for further experiments. 37259412 14 62 theme active 1670:1675 arg1 concentration 1677:1689 The lowest active concentration 1659:1689 The lowest active concentration of decoction (50 µg/mL) 1659:1713 The lowest active concentration of decoction (50 µg/mL) was selected for further experiments. 37259412 11 63 theme acetone 1377:1383 arg1 extracts 1385:1392 the previously obtained ethanol and acetone extracts 1341:1392 extracts 1385:1392 Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. 37259412 5 64 theme acetone 391:397 arg1 extracts 399:406 ethanol and acetone extracts 379:406 ethanol and acetone extracts from this herbal drug 379:428 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 8 65 theme type 1013:1016 arg1 expression 1022:1031 the collagen type III expression 1000:1031 the collagen type III expression 1000:1031 Moreover, the collagen type III expression was examined using immunocytochemical staining. 37259412 11 66 theme ethanol 1365:1371 arg1 analysis 1315:1322 HPLC-RI analysis 1307:1322 HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts 1307:1392 Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. 37259412 6 67 theme healing 728:734 arg1 activity 736:743 its in vitro gingival wound healing activity 700:743 its in vitro gingival wound healing activity 700:743 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 5 68 theme gum 462:464 arg1 wounds 466:471 oral gum wounds 457:471 oral gum wounds 457:471 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 12 69 theme HGF 1558:1560 arg1 viability 1567:1575 HGF cell viability 1558:1575 HGF cell viability 1558:1575 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. 37259412 6 70 theme gingival 713:720 arg1 healing 728:734 its in vitro gingival wound healing 700:734 its in vitro gingival wound healing activity 700:743 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 7 71 theme human 781:785 arg1 fibroblasts 796:806 the primary human gingival fibroblasts 769:806 the primary human gingival fibroblasts (HGF) incubated with a decoction 769:839 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 71 theme human 781:785 arg1 HGF 809:811 HGF 809:811 HGF 809:811 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 13 72 dep 2000 1646:1649 arg1 to 1643:1644 to 1643:1644 to 1643:1644 No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). 37259412 18 73 theme significant 2104:2114 arg1 effect 2116:2121 a significant effect 2102:2121 a significant effect 2102:2121 In our opinion, they may have a significant effect on the oral wound healing parameters analyzed in vitro. 37259412 17 74 theme polysaccharides 2041:2055 arg1 levels 2031:2036 high levels 2026:2036 high levels of polysaccharides 2026:2055 In contrast, high levels of polysaccharides were observed. 37259412 7 75 theme wound 968:972 arg1 migration 957:965 cell migration 952:965 cell migration (wound healing assay) 952:987 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 75 theme wound 968:972 arg1 assay 982:986 wound healing assay 968:986 wound healing assay 968:986 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 9 76 theme HPLC/DAD/ESI-HR-QTOF-MS 1174:1196 arg1 method 1198:1203 the validated HPLC/DAD/ESI-HR-QTOF-MS method 1160:1203 the validated HPLC/DAD/ESI-HR-QTOF-MS method 1160:1203 The studied decoction was qualitatively and quantitatively characterized using the validated HPLC/DAD/ESI-HR-QTOF-MS method. 37259412 18 77 theme healing 2141:2147 arg1 parameters 2149:2158 the oral wound healing parameters 2126:2158 the oral wound healing parameters analyzed in vitro 2126:2176 In our opinion, they may have a significant effect on the oral wound healing parameters analyzed in vitro. 37259412 11 78 theme HPLC-RI 1307:1313 arg1 analysis 1315:1322 HPLC-RI analysis 1307:1322 HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts 1307:1392 Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. 37259412 18 79 theme oral 2130:2133 arg1 healing 2141:2147 oral wound healing 2130:2147 the oral wound healing parameters analyzed in vitro 2126:2176 In our opinion, they may have a significant effect on the oral wound healing parameters analyzed in vitro. 37259412 12 80 theme 24 1509:1510 arg1 h 1512:1512 h 1512:1512 h 1512:1512 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. 37259412 6 81 theme present 596:602 arg1 study 604:608 the present study 592:608 the present study 592:608 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 7 82 theme laser 915:919 arg1 microscope-CLSM 930:944 the confocal laser scanning microscope-CLSM 902:944 the confocal laser scanning microscope-CLSM 902:944 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 7 82 theme laser 915:919 arg1 proliferation 887:899 cell proliferation 882:899 cell proliferation (the confocal laser scanning microscope-CLSM) 882:945 We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). 37259412 12 83 theme decoction 1493:1501 arg1 concentration 1452:1464 Low concentration 1448:1464 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation 1448:1523 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. 37259412 18 84 contain have 2097:2100 arg1 they 2088:2091 they 2088:2091 they 2088:2091 In our opinion, they may have a significant effect on the oral wound healing parameters analyzed in vitro. 37259412 18 84 contain have 2097:2100 arg2 effect 2116:2121 a significant effect 2102:2121 a significant effect 2102:2121 In our opinion, they may have a significant effect on the oral wound healing parameters analyzed in vitro. 37259412 10 85 theme Folin-Ciocalteu 1210:1224 arg1 assay 1226:1230 The Folin-Ciocalteu assay 1206:1230 The Folin-Ciocalteu assay 1206:1230 The Folin-Ciocalteu assay was used to determine the total phenols and tannins content. 37259412 5 86 theme in 342:343 arg1 study 351:355 a recent in vitro study 333:355 a recent in vitro study 333:355 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 10 87 used used 1236:1239 arg2 assay 1226:1230 The Folin-Ciocalteu assay 1206:1230 The Folin-Ciocalteu assay 1206:1230 The Folin-Ciocalteu assay was used to determine the total phenols and tannins content. 37259412 6 88 theme rhizomes 646:653 arg1 decoction 613:621 a decoction 611:621 a decoction of Reynoutria japonica rhizomes 611:653 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 0 89 theme Wound 5:9 arg1 Healing 11:17 Oral Wound Healing 0:17 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix 0:66 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix Decoction-In Vitro Study. 37259412 4 90 theme applications 266:277 arg1 one 255:257 one 255:257 one 255:257 In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. 37259412 4 90 theme applications 266:277 arg1 applications 266:277 the applications 262:277 the applications for Reynoutria japonica rhizomes 262:310 In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. 37259412 15 91 theme collagen 1863:1870 arg1 synthesis 1850:1858 the synthesis 1846:1858 the synthesis of collagen III 1846:1874 It significantly stimulated human gingival fibroblasts to proliferate, migrate, and increase the synthesis of collagen III. 37259412 6 92 theme Reynoutria 626:635 arg1 rhizomes 646:653 Reynoutria japonica rhizomes 626:653 Reynoutria japonica rhizomes 626:653 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 14 93 theme further 1732:1738 arg1 experiments 1740:1750 further experiments 1732:1750 further experiments 1732:1750 The lowest active concentration of decoction (50 µg/mL) was selected for further experiments. 37259412 19 94 theme raw 2226:2228 arg1 material 2230:2237 this raw material 2221:2237 this raw material 2221:2237 The results obtained encourage the use of this raw material in its traditional, safe form-decoction. 37259412 4 95 theme traditional 233:243 arg1 medicine 245:252 traditional medicine 233:252 traditional medicine 233:252 In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. 37259412 16 96 theme ethanol 1968:1974 arg1 extracts 1988:1995 the ethanol and acetone extracts 1964:1995 the ethanol and acetone extracts tested earlier 1964:2010 Phytochemical analysis showed significantly fewer polyphenols in the decoction than in the ethanol and acetone extracts tested earlier. 37259412 10 97 theme phenols 1264:1270 arg1 content 1284:1290 the total phenols and tannins content 1254:1290 the total phenols and tannins content 1254:1290 The Folin-Ciocalteu assay was used to determine the total phenols and tannins content. 37259412 19 98 theme traditional 2246:2256 arg1 form-decoction 2264:2277 its traditional, safe form-decoction 2242:2277 its traditional, safe form-decoction 2242:2277 The results obtained encourage the use of this raw material in its traditional, safe form-decoction. 37259412 11 99 theme decoction 1327:1335 arg1 analysis 1315:1322 HPLC-RI analysis 1307:1322 HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts 1307:1392 Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. 37259412 2 100 theme japonica 159:166 arg1 Houtt 168:172 Reynoutria japonica Houtt 148:172 Reynoutria japonica Houtt 148:172 rhizomes of Reynoutria japonica Houtt.) 37259412 0 101 theme Rhizoma 51:57 arg1 Potential 19:27 Oral Wound Healing Potential 0:27 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix 0:66 Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix Decoction-In Vitro Study. 37259412 3 102 from material 200:207 arg1 China 223:227 China 223:227 China 223:227 is a pharmacopoeial raw material in Europe and China. 37259412 3 102 from material 200:207 arg1 Europe 212:217 Europe 212:217 Europe 212:217 is a pharmacopoeial raw material in Europe and China. 37259412 12 103 from increase 1546:1553 arg1 viability 1567:1575 HGF cell viability 1558:1575 HGF cell viability 1558:1575 Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. 37259412 5 104 from drug 425:428 arg1 extracts 399:406 ethanol and acetone extracts 379:406 ethanol and acetone extracts from this herbal drug 379:428 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 4 105 theme wound 315:319 arg1 healing 321:327 wound healing 315:327 wound healing 315:327 In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. 37259412 13 106 located observed 1602:1609 arg1 µg/mL 1651:1655 up to 2000 µg/mL 1640:1655 up to 2000 µg/mL 1640:1655 No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). 37259412 13 106 located observed 1602:1609 arg2 effect 1591:1596 No cytotoxic effect 1578:1596 No cytotoxic effect 1578:1596 No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). 37259412 13 106 located observed 1602:1609 arg1 concentration 1625:1637 any tested concentration 1614:1637 any tested concentration (up to 2000 µg/mL) 1614:1656 No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). 37259412 5 107 dep in 342:343 arg1 vitro 345:349 vitro 345:349 vitro 345:349 In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. 37259412 19 108 theme material 2230:2237 arg1 use 2214:2216 the use 2210:2216 the use of this raw material in its traditional, safe form-decoction 2210:2277 The results obtained encourage the use of this raw material in its traditional, safe form-decoction. 37259412 14 109 theme decoction 1694:1702 arg1 µg/mL 1708:1712 50 µg/mL 1705:1712 50 µg/mL 1705:1712 The lowest active concentration of decoction (50 µg/mL) was selected for further experiments. 37259412 14 109 theme decoction 1694:1702 arg1 concentration 1677:1689 The lowest active concentration 1659:1689 The lowest active concentration of decoction (50 µg/mL) 1659:1713 The lowest active concentration of decoction (50 µg/mL) was selected for further experiments. 37259412 4 110 theme Reynoutria 283:292 arg1 rhizomes 303:310 Reynoutria japonica rhizomes 283:310 Reynoutria japonica rhizomes 283:310 In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. 37259412 6 111 dep tests 681:685 arg1 determine 690:698 determine 690:698 to determine its in vitro gingival wound healing activity 687:743 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 37259412 11 112 theme obtained 1356:1363 arg1 ethanol 1365:1371 the previously obtained ethanol and acetone extracts 1341:1392 ethanol 1365:1371 Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. 37259412 6 113 theme detailed 672:679 arg1 tests 681:685 detailed tests 672:685 detailed tests to determine its in vitro gingival wound healing activity 672:743 However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. 36529880 7 0 theme lubrication 1484:1494 arg1 absorption 1387:1396 water absorption 1381:1396 water absorption of flaxseed protein/gum polysaccharides 1381:1436 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 7 0 theme lubrication 1484:1494 arg1 interruption 1446:1457 the interruption 1442:1457 the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, 1442:1545 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 3 1 theme food 667:670 arg1 matrix 672:677 food matrix 667:677 food matrix 667:677 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 6 2 theme influencing 1260:1270 arg1 mechanisms 1272:1281 the potential influencing mechanisms 1246:1281 the potential influencing mechanisms of flaxseed (flour) on different substrate components 1246:1335 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 2 3 theme several 313:319 arg1 limitations 321:331 several limitations 313:331 several limitations 313:331 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 8 4 theme fortified 1679:1687 arg1 products 1694:1701 fortified food products 1679:1701 fortified food products 1679:1701 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 7 5 theme polysaccharides 1422:1436 arg1 absorption 1387:1396 water absorption 1381:1396 water absorption of flaxseed protein/gum polysaccharides 1381:1436 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 7 5 theme polysaccharides 1422:1436 arg1 interruption 1446:1457 the interruption 1442:1457 the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, 1442:1545 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 8 6 theme products 1694:1701 arg1 quality 1641:1647 quality 1641:1647 quality 1641:1647 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 8 6 theme products 1694:1701 arg1 attributes 1665:1674 nutritional attributes 1653:1674 nutritional attributes 1653:1674 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 7 7 theme gluten 1462:1467 arg1 network 1469:1475 gluten network 1462:1475 gluten network 1462:1475 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 4 8 theme fortified 832:840 arg1 products 842:849 fortified products 832:849 fortified products 832:849 The potential interaction mechanism between the subject and object components in fortified products has not been elucidated yet. 36529880 7 9 theme flaxseed 1401:1408 arg1 polysaccharides 1422:1436 flaxseed protein/gum polysaccharides 1401:1436 flaxseed protein/gum polysaccharides 1401:1436 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 9 10 theme optimal 1892:1898 arg1 properties 1923:1932 the optimal edible and nutritional properties 1888:1932 the optimal edible and nutritional properties of fortified food products 1888:1959 This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products. 36529880 6 11 theme typical 1135:1141 arg1 noodle 1175:1180 noodle 1175:1180 noodle 1175:1180 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 6 11 theme typical 1135:1141 arg1 products 1148:1155 several typical food products 1127:1155 several typical food products 1127:1155 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 6 11 theme typical 1135:1141 arg1 baked 1168:1172 baked 1168:1172 baked 1168:1172 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 6 11 theme typical 1135:1141 arg1 products 1193:1200 dairy products 1187:1200 dairy products 1187:1200 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 3 12 theme fortified 726:734 arg1 products 741:748 fortified food products 726:748 fortified food products 726:748 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 1 13 theme fatty 146:150 arg1 acid 152:155 omega-3 fatty acid 138:155 omega-3 fatty acid 138:155 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 2 14 theme nutrients 526:534 arg1 entrapment 512:521 entrapment 512:521 entrapment of nutrients within food matrix 512:553 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 2 14 theme nutrients 526:534 arg1 factors 500:506 naturally occurring antinutritional factors 464:506 naturally occurring antinutritional factors 464:506 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 6 15 theme different 1306:1314 arg1 components 1326:1335 different substrate components 1306:1335 different substrate components 1306:1335 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 2 16 from market 448:453 arg1 development 378:388 the development 374:388 the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix 374:553 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 7 17 theme altered 1357:1363 arg1 balance 1365:1371 the altered balance 1353:1371 the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, 1353:1545 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 9 18 theme fortified 1937:1945 arg1 products 1952:1959 fortified food products 1937:1959 fortified food products 1937:1959 This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products. 36529880 8 19 from impact 1587:1592 arg1 quality 1641:1647 quality 1641:1647 quality 1641:1647 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 8 19 from impact 1587:1592 arg1 attributes 1665:1674 nutritional attributes 1653:1674 nutritional attributes 1653:1674 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 5 20 theme multiple 1051:1058 arg1 products 1075:1082 multiple fortified food products 1051:1082 multiple fortified food products 1051:1082 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 4 21 from components 818:827 arg1 products 842:849 fortified products 832:849 fortified products 832:849 The potential interaction mechanism between the subject and object components in fortified products has not been elucidated yet. 36529880 6 22 theme dairy 1187:1191 arg1 products 1193:1200 dairy products 1187:1200 dairy products 1187:1200 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 9 23 theme products 1952:1959 arg1 properties 1923:1932 the optimal edible and nutritional properties 1888:1932 the optimal edible and nutritional properties of fortified food products 1888:1959 This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products. 36529880 3 24 theme products 741:748 arg1 qualities 713:721 the edible qualities 702:721 the edible qualities of fortified food products 702:748 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 2 25 theme food 543:546 arg1 matrix 548:553 food matrix 543:553 food matrix 543:553 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 3 26 theme existing 594:601 arg1 forms 603:607 different existing forms 584:607 different existing forms 584:607 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 8 27 dep quality 1641:1647 arg1 the 1637:1639 the 1637:1639 the 1637:1639 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 0 28 theme whole 48:52 arg1 products 63:70 whole flaxseed products 48:70 whole flaxseed products 48:70 Composition, processing, and quality control of whole flaxseed products used to fortify foods. 36529880 0 29 theme products 63:70 arg1 processing 13:22 processing 13:22 processing 13:22 Composition, processing, and quality control of whole flaxseed products used to fortify foods. 36529880 0 29 theme products 63:70 arg1 Composition 0:10 Composition 0:10 Composition 0:10 Composition, processing, and quality control of whole flaxseed products used to fortify foods. 36529880 0 29 theme products 63:70 arg1 control 37:43 quality control 29:43 quality control 29:43 Composition, processing, and quality control of whole flaxseed products used to fortify foods. 36529880 1 30 theme good 123:126 arg1 source 128:133 a good source 121:133 a good source of omega-3 fatty acid 121:155 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 3 31 with flaxseed 562:569 arg1 forms 603:607 different existing forms 584:607 different existing forms 584:607 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 5 32 theme food 1070:1073 arg1 products 1075:1082 multiple fortified food products 1051:1082 multiple fortified food products 1051:1082 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 2 33 theme occurring 474:482 arg1 factors 500:506 naturally occurring antinutritional factors 464:506 naturally occurring antinutritional factors 464:506 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 2 34 from products 425:432 arg1 market 448:453 the global market 437:453 the global market 437:453 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 4 35 theme potential 755:763 arg1 mechanism 777:785 The potential interaction mechanism 751:785 The potential interaction mechanism between the subject and object components in fortified products 751:849 The potential interaction mechanism between the subject and object components in fortified products has not been elucidated yet. 36529880 2 36 theme -enriched 415:423 arg1 entrapment 512:521 entrapment 512:521 entrapment of nutrients within food matrix 512:553 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 2 36 theme -enriched 415:423 arg1 products 425:432 whole flaxseed (flour)-enriched products 393:432 whole flaxseed (flour)-enriched products 393:432 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 2 36 theme -enriched 415:423 arg1 factors 500:506 naturally occurring antinutritional factors 464:506 naturally occurring antinutritional factors 464:506 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 7 37 dep network 1469:1475 arg1 forth 1540:1544 forth 1540:1544 forth 1540:1544 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 9 38 theme useful 1804:1809 arg1 information 1811:1821 useful information 1804:1821 useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products 1804:1959 This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products. 36529880 1 39 used used 238:241 arg2 flour 111:115 flour 111:115 flour 111:115 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 1 39 used used 238:241 arg2 flaxseed 101:108 Whole flaxseed 95:108 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes 95:227 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 5 40 theme component 929:937 arg1 changes 939:945 component changes 929:945 component changes 929:945 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 2 41 theme global 441:446 arg1 market 448:453 the global market 437:453 the global market 437:453 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 1 42 theme health 263:268 arg1 promotion 270:278 health promotion 263:278 health promotion 263:278 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 7 43 theme syneresis 1522:1530 arg1 absorption 1387:1396 water absorption 1381:1396 water absorption of flaxseed protein/gum polysaccharides 1381:1436 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 7 43 theme syneresis 1522:1530 arg1 interruption 1446:1457 the interruption 1442:1457 the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, 1442:1545 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 7 44 theme complexes 1511:1519 arg1 absorption 1387:1396 water absorption 1381:1396 water absorption of flaxseed protein/gum polysaccharides 1381:1436 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 7 44 theme complexes 1511:1519 arg1 interruption 1446:1457 the interruption 1442:1457 the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, 1442:1545 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 5 45 theme potential 1003:1011 arg1 influences 1013:1022 their potential influences 997:1022 their potential influences on the edible qualities of multiple fortified food products 997:1082 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 1 46 theme excellent 181:189 arg1 attributes 218:227 excellent nutritional and functional attributes 181:227 excellent nutritional and functional attributes 181:227 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 7 47 theme protein/gum 1410:1420 arg1 polysaccharides 1422:1436 flaxseed protein/gum polysaccharides 1401:1436 flaxseed protein/gum polysaccharides 1401:1436 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 9 48 theme flaxseed 1862:1869 arg1 application 1841:1851 the application 1837:1851 the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products 1837:1959 This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products. 36529880 3 49 theme techno-functional 634:650 arg1 performance 652:662 the techno-functional performance 630:662 the techno-functional performance of food matrix 630:677 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 2 50 theme contemporary 337:348 arg1 challenges 350:359 contemporary challenges 337:359 contemporary challenges 337:359 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 6 51 from mechanisms 1272:1281 arg1 components 1326:1335 different substrate components 1306:1335 different substrate components 1306:1335 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 7 52 theme lipid 1478:1482 arg1 lubrication 1484:1494 lipid lubrication 1478:1494 lipid lubrication 1478:1494 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 8 53 theme nutritional 1653:1663 arg1 attributes 1665:1674 nutritional attributes 1653:1674 nutritional attributes 1653:1674 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 7 54 theme network 1469:1475 arg1 absorption 1387:1396 water absorption 1381:1396 water absorption of flaxseed protein/gum polysaccharides 1381:1436 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 7 54 theme network 1469:1475 arg1 interruption 1446:1457 the interruption 1442:1457 the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, 1442:1545 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 3 55 theme matrix 672:677 arg1 performance 652:662 the techno-functional performance 630:662 the techno-functional performance of food matrix 630:677 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 6 56 theme potential 1250:1258 arg1 mechanisms 1272:1281 the potential influencing mechanisms 1246:1281 the potential influencing mechanisms of flaxseed (flour) on different substrate components 1246:1335 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 3 57 theme edible 706:711 arg1 qualities 713:721 the edible qualities 702:721 the edible qualities of fortified food products 702:748 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 8 58 theme food 1689:1692 arg1 products 1694:1701 fortified food products 1679:1701 fortified food products 1679:1701 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 6 59 theme food 1143:1146 arg1 noodle 1175:1180 noodle 1175:1180 noodle 1175:1180 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 6 59 theme food 1143:1146 arg1 products 1148:1155 several typical food products 1127:1155 several typical food products 1127:1155 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 6 59 theme food 1143:1146 arg1 baked 1168:1172 baked 1168:1172 baked 1168:1172 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 6 59 theme food 1143:1146 arg1 products 1193:1200 dairy products 1187:1200 dairy products 1187:1200 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 9 60 theme edible 1900:1905 arg1 properties 1923:1932 the optimal edible and nutritional properties 1888:1932 the optimal edible and nutritional properties of fortified food products 1888:1959 This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products. 36529880 1 61 theme omega-3 138:144 arg1 acid 152:155 omega-3 fatty acid 138:155 omega-3 fatty acid 138:155 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 6 62 theme several 1127:1133 arg1 noodle 1175:1180 noodle 1175:1180 noodle 1175:1180 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 6 62 theme several 1127:1133 arg1 products 1148:1155 several typical food products 1127:1155 several typical food products 1127:1155 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 6 62 theme several 1127:1133 arg1 baked 1168:1172 baked 1168:1172 baked 1168:1172 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 6 62 theme several 1127:1133 arg1 products 1193:1200 dairy products 1187:1200 dairy products 1187:1200 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 9 63 theme nutritional 1911:1921 arg1 properties 1923:1932 the optimal edible and nutritional properties 1888:1932 the optimal edible and nutritional properties of fortified food products 1888:1959 This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products. 36529880 3 64 theme food 736:739 arg1 products 741:748 fortified food products 726:748 fortified food products 726:748 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 6 65 theme substrate 1316:1324 arg1 components 1326:1335 different substrate components 1306:1335 different substrate components 1306:1335 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 1 66 theme acid 152:155 arg1 source 128:133 a good source 121:133 a good source of omega-3 fatty acid 121:155 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 1 66 theme acid 152:155 arg1 phytochemicals 161:174 phytochemicals 161:174 phytochemicals with excellent nutritional and functional attributes 161:227 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 7 67 theme water 1381:1385 arg1 absorption 1387:1396 water absorption 1381:1396 water absorption of flaxseed protein/gum polysaccharides 1381:1436 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 0 68 used used 72:75 arg2 Composition 0:10 Composition 0:10 Composition 0:10 Composition, processing, and quality control of whole flaxseed products used to fortify foods. 36529880 0 68 used used 72:75 arg2 control 37:43 quality control 29:43 quality control 29:43 Composition, processing, and quality control of whole flaxseed products used to fortify foods. 36529880 0 68 used used 72:75 arg2 processing 13:22 processing 13:22 processing 13:22 Composition, processing, and quality control of whole flaxseed products used to fortify foods. 36529880 8 69 theme possible 1721:1728 arg1 solutions 1730:1738 the possible solutions 1717:1738 the possible solutions against negative influences 1717:1766 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 9 70 theme food 1947:1950 arg1 products 1952:1959 fortified food products 1937:1959 fortified food products 1937:1959 This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products. 36529880 5 71 theme fortified 1060:1068 arg1 products 1075:1082 multiple fortified food products 1051:1082 multiple fortified food products 1051:1082 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 3 72 theme Whole 556:560 arg1 flour 572:576 flour 572:576 flour 572:576 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 3 72 theme Whole 556:560 arg1 flaxseed 562:569 Whole flaxseed 556:569 Whole flaxseed (flour) with different existing forms 556:607 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 1 73 theme Whole 95:99 arg1 flour 111:115 flour 111:115 flour 111:115 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 1 73 theme Whole 95:99 arg1 flaxseed 101:108 Whole flaxseed 95:108 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes 95:227 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 6 74 theme flaxseed 1286:1293 arg1 mechanisms 1272:1281 the potential influencing mechanisms 1246:1281 the potential influencing mechanisms of flaxseed (flour) on different substrate components 1246:1335 In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. 36529880 3 75 theme different 584:592 arg1 forms 603:607 different existing forms 584:607 different existing forms 584:607 Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. 36529880 8 76 theme negative 1748:1755 arg1 influences 1757:1766 negative influences 1748:1766 negative influences 1748:1766 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 0 77 theme flaxseed 54:61 arg1 products 63:70 whole flaxseed products 48:70 whole flaxseed products 48:70 Composition, processing, and quality control of whole flaxseed products used to fortify foods. 36529880 5 78 theme edible 1031:1036 arg1 qualities 1038:1046 the edible qualities 1027:1046 the edible qualities of multiple fortified food products 1027:1082 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 5 79 from influences 1013:1022 arg1 qualities 1038:1046 the edible qualities 1027:1046 the edible qualities of multiple fortified food products 1027:1082 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 5 80 dep structure 915:923 arg1 the 902:904 the 902:904 the 902:904 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 2 81 theme antinutritional 484:498 arg1 factors 500:506 naturally occurring antinutritional factors 464:506 naturally occurring antinutritional factors 464:506 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 5 82 theme products 1075:1082 arg1 qualities 1038:1046 the edible qualities 1027:1046 the edible qualities of multiple fortified food products 1027:1082 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 5 83 theme flaxseed 950:957 arg1 structure 915:923 physical structure 906:923 physical structure 906:923 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 5 83 theme flaxseed 950:957 arg1 changes 939:945 component changes 929:945 component changes 929:945 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 5 84 theme physical 906:913 arg1 structure 915:923 physical structure 906:923 physical structure 906:923 Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. 36529880 1 85 with phytochemicals 161:174 arg1 attributes 218:227 excellent nutritional and functional attributes 181:227 excellent nutritional and functional attributes 181:227 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 2 86 theme whole 393:397 arg1 entrapment 512:521 entrapment 512:521 entrapment of nutrients within food matrix 512:553 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 2 86 theme whole 393:397 arg1 products 425:432 whole flaxseed (flour)-enriched products 393:432 whole flaxseed (flour)-enriched products 393:432 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 2 86 theme whole 393:397 arg1 factors 500:506 naturally occurring antinutritional factors 464:506 naturally occurring antinutritional factors 464:506 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 0 87 theme quality 29:35 arg1 control 37:43 quality control 29:43 quality control 29:43 Composition, processing, and quality control of whole flaxseed products used to fortify foods. 36529880 4 88 theme subject 799:805 arg1 components 818:827 the subject and object components 795:827 the subject and object components in fortified products 795:849 The potential interaction mechanism between the subject and object components in fortified products has not been elucidated yet. 36529880 2 89 theme products 425:432 arg1 development 378:388 the development 374:388 the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix 374:553 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 8 90 theme overall 1579:1585 arg1 impact 1587:1592 The overall impact 1575:1592 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences 1575:1766 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 4 91 theme object 811:816 arg1 components 818:827 the subject and object components 795:827 the subject and object components in fortified products 795:849 The potential interaction mechanism between the subject and object components in fortified products has not been elucidated yet. 36529880 1 92 theme disease 284:290 arg1 prevention 292:301 disease prevention 284:301 disease prevention 284:301 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 1 93 with source 128:133 arg1 attributes 218:227 excellent nutritional and functional attributes 181:227 excellent nutritional and functional attributes 181:227 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 9 94 theme whole 1856:1860 arg1 flaxseed 1862:1869 whole flaxseed 1856:1869 whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products 1856:1959 This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products. 36529880 9 94 theme whole 1856:1860 arg1 flour 1872:1876 flour 1872:1876 flour 1872:1876 This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products. 36529880 4 95 theme interaction 765:775 arg1 mechanism 777:785 The potential interaction mechanism 751:785 The potential interaction mechanism between the subject and object components in fortified products 751:849 The potential interaction mechanism between the subject and object components in fortified products has not been elucidated yet. 36529880 1 96 theme nutritional 191:201 arg1 attributes 218:227 excellent nutritional and functional attributes 181:227 excellent nutritional and functional attributes 181:227 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36529880 7 97 theme lipid-amylose 1497:1509 arg1 complexes 1511:1519 lipid-amylose complexes 1497:1519 lipid-amylose complexes 1497:1519 In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. 36529880 2 98 from development 378:388 arg1 market 448:453 the global market 437:453 the global market 437:453 However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. 36529880 8 99 theme whole 1611:1615 arg1 flour 1627:1631 flour 1627:1631 flour 1627:1631 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 8 99 theme whole 1611:1615 arg1 flaxseed 1617:1624 whole flaxseed 1611:1624 whole flaxseed (flour) 1611:1632 The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. 36529880 1 100 theme functional 207:216 arg1 attributes 218:227 excellent nutritional and functional attributes 181:227 excellent nutritional and functional attributes 181:227 Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. 36982475 11 0 theme plasma 1409:1414 arg1 levels 1416:1421 IGF2 increased plasma levels 1394:1421 IGF2 increased plasma levels 1394:1421 Further experiments corroborated this hypothesis as IGF2 increased plasma levels were observed in CKD patients. 36982475 5 1 theme identified 626:635 arg1 glycopeptides 637:649 the identified glycopeptides 622:649 the identified glycopeptides 622:649 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 3 2 theme study 287:291 arg1 aim 275:277 The aim 271:277 The aim of this study 271:291 The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. 36982475 12 3 theme available 1493:1501 arg1 data 1519:1522 available transcriptomics data 1493:1522 available transcriptomics data 1493:1522 Protease predictions, considering also available transcriptomics data, suggest activation of cathepsin S with CKD, meriting further investigation. 36982475 5 4 theme glycopeptides 637:649 arg1 correlation 661:671 their correlation 655:671 their correlation with Age, eGFR and Albuminuria 655:702 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 5 4 theme glycopeptides 637:649 arg1 Distribution 606:617 Distribution 606:617 Distribution of the identified glycopeptides 606:649 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 11 5 theme CKD 1440:1442 arg1 patients 1444:1451 CKD patients 1440:1451 CKD patients 1440:1451 Further experiments corroborated this hypothesis as IGF2 increased plasma levels were observed in CKD patients. 36982475 8 6 theme positive 1057:1064 arg1 correlation 1066:1076 positive correlation 1057:1076 positive correlation with Age 1057:1085 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. 36982475 7 7 dep exposed 924:930 arg1 surface 916:922 surface 916:922 surface 916:922 Glycosylation occurred at the surface exposed IGF2 Threonine 96 position. 36982475 12 8 theme S 1557:1557 arg1 activation 1533:1542 activation 1533:1542 activation of cathepsin S with CKD 1533:1566 Protease predictions, considering also available transcriptomics data, suggest activation of cathepsin S with CKD, meriting further investigation. 36982475 3 9 theme O-linked 317:324 arg1 glycopeptides 326:338 urinary O-linked glycopeptides 309:338 urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations 309:420 The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. 36982475 7 10 theme IGF2 932:935 arg1 position 950:957 the surface exposed IGF2 Threonine 96 position 912:957 the surface exposed IGF2 Threonine 96 position 912:957 Glycosylation occurred at the surface exposed IGF2 Threonine 96 position. 36982475 1 11 from % 146:146 arg1 prevalent 131:139 prevalent 131:139 prevalent 131:139 Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. 36982475 10 12 theme deteriorating 1217:1229 arg1 function 1238:1245 deteriorating kidney function 1217:1245 deteriorating kidney function 1217:1245 These results suggest that with aging and deteriorating kidney function, alterations in IGF2 proteoforms take place, which may reflect changes in mature IGF2 protein. 36982475 6 13 from proteins 799:806 arg1 glycopeptides 768:780 17 O-linked glycopeptides 756:780 17 O-linked glycopeptides from 7 different proteins 756:806 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 4 14 theme manual 572:577 arg1 inspection 579:588 manual inspection 572:588 manual inspection of the spectra 572:603 Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the spectra. 36982475 12 15 with activation 1533:1542 arg1 CKD 1564:1566 CKD 1564:1566 CKD 1564:1566 Protease predictions, considering also available transcriptomics data, suggest activation of cathepsin S with CKD, meriting further investigation. 36982475 4 16 from subjects 468:475 arg1 samples 429:435 Urine samples 423:435 Urine samples from eight CKD and two healthy subjects 423:475 Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the spectra. 36982475 0 17 with Association 77:87 arg1 CKD 94:96 CKD 94:96 CKD 94:96 Glycosylation Analysis of Urinary Peptidome Highlights IGF2 Glycopeptides in Association with CKD. 36982475 10 18 theme IGF2 1328:1331 arg1 protein 1333:1339 mature IGF2 protein 1321:1339 mature IGF2 protein 1321:1339 These results suggest that with aging and deteriorating kidney function, alterations in IGF2 proteoforms take place, which may reflect changes in mature IGF2 protein. 36982475 8 19 with correlation 1066:1076 arg1 Age 1083:1085 Age 1083:1085 Age 1083:1085 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. 36982475 9 20 with association 1152:1162 arg1 eGFR 1169:1172 eGFR 1169:1172 eGFR 1169:1172 The IGF2 glycopeptide (tPPTVLPDNFPRYP) showed a strong negative association with eGFR. 36982475 2 21 from role 181:184 arg1 mechanisms 221:230 causal mechanisms 214:230 causal mechanisms of CKD progression 214:249 The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. 36982475 9 22 theme IGF2 1092:1095 arg1 tPPTVLPDNFPRYP 1111:1124 tPPTVLPDNFPRYP 1111:1124 tPPTVLPDNFPRYP 1111:1124 The IGF2 glycopeptide (tPPTVLPDNFPRYP) showed a strong negative association with eGFR. 36982475 9 22 theme IGF2 1092:1095 arg1 glycopeptide 1097:1108 The IGF2 glycopeptide 1088:1108 The IGF2 glycopeptide (tPPTVLPDNFPRYP) 1088:1125 The IGF2 glycopeptide (tPPTVLPDNFPRYP) showed a strong negative association with eGFR. 36982475 11 23 theme Further 1342:1348 arg1 experiments 1350:1360 Further experiments 1342:1360 Further experiments 1342:1360 Further experiments corroborated this hypothesis as IGF2 increased plasma levels were observed in CKD patients. 36982475 3 24 link O-linked 317:324 arg1 glycopeptides 326:338 urinary O-linked glycopeptides 309:338 urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations 309:420 The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. 36982475 5 25 with correlation 661:671 arg1 Age 678:680 Age 678:680 Age 678:680 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 5 25 with correlation 661:671 arg1 Albuminuria 692:702 Albuminuria 692:702 Albuminuria 692:702 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 5 25 with correlation 661:671 arg1 eGFR 683:686 eGFR 683:686 eGFR 683:686 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 3 26 theme manifestations 407:420 arg1 characterization 373:388 better characterization 366:388 better characterization of CKD molecular manifestations 366:420 The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. 36982475 3 27 theme urinary 309:315 arg1 glycopeptides 326:338 urinary O-linked glycopeptides 309:338 urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations 309:420 The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. 36982475 4 28 theme healthy 460:466 arg1 subjects 468:475 two healthy subjects 456:475 two healthy subjects 456:475 Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the spectra. 36982475 8 29 gly glycopeptides 966:978 arg2 DVStPPTVLPDNFPRYP 1028:1044 DVStPPTVLPDNFPRYP 1028:1044 DVStPPTVLPDNFPRYP 1028:1044 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. 36982475 8 29 gly glycopeptides 966:978 arg2 DVStPPTVLPDNFPRYPVG 1004:1022 DVStPPTVLPDNFPRYPVG 1004:1022 DVStPPTVLPDNFPRYPVG 1004:1022 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. 36982475 8 29 gly glycopeptides 966:978 arg2 DVStPPTVLPDNFPRYPVGKF 981:1001 DVStPPTVLPDNFPRYPVGKF 981:1001 DVStPPTVLPDNFPRYPVGKF 981:1001 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. 36982475 8 29 gly glycopeptides 966:978 arg2 glycopeptides 966:978 Three glycopeptides 960:978 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) 960:1045 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. 36982475 7 30 theme exposed 924:930 arg1 position 950:957 the surface exposed IGF2 Threonine 96 position 912:957 the surface exposed IGF2 Threonine 96 position 912:957 Glycosylation occurred at the surface exposed IGF2 Threonine 96 position. 36982475 2 31 theme progression 239:249 arg1 mechanisms 221:230 causal mechanisms 214:230 causal mechanisms of CKD progression 214:249 The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. 36982475 7 32 theme Threonine 937:945 arg1 position 950:957 the surface exposed IGF2 Threonine 96 position 912:957 the surface exposed IGF2 Threonine 96 position 912:957 Glycosylation occurred at the surface exposed IGF2 Threonine 96 position. 36982475 6 33 theme O-linked 759:766 arg1 glycopeptides 768:780 17 O-linked glycopeptides 756:780 17 O-linked glycopeptides from 7 different proteins 756:806 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 3 34 theme better 366:371 arg1 characterization 373:388 better characterization 366:388 better characterization of CKD molecular manifestations 366:420 The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. 36982475 12 35 theme Protease 1454:1461 arg1 predictions 1463:1473 Protease predictions 1454:1473 Protease predictions 1454:1473 Protease predictions, considering also available transcriptomics data, suggest activation of cathepsin S with CKD, meriting further investigation. 36982475 3 36 theme CKD 393:395 arg1 manifestations 407:420 CKD molecular manifestations 393:420 CKD molecular manifestations 393:420 The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. 36982475 0 37 theme Glycosylation 0:12 arg1 Analysis 14:21 Glycosylation Analysis 0:21 Glycosylation Analysis of Urinary Peptidome 0:42 Glycosylation Analysis of Urinary Peptidome Highlights IGF2 Glycopeptides in Association with CKD. 36982475 6 38 dep identified 813:822 arg1 derived 825:831 derived 825:831 derived primarily from Insulin-like growth factor-II (IGF2) 825:883 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 4 39 from CKD 448:450 arg1 samples 429:435 Urine samples 423:435 Urine samples from eight CKD and two healthy subjects 423:475 Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the spectra. 36982475 1 40 theme Chronic 99:105 arg1 CKD 123:125 CKD 123:125 CKD 123:125 Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. 36982475 1 40 theme Chronic 99:105 arg1 disease 114:120 Chronic kidney disease 99:120 Chronic kidney disease (CKD) 99:126 Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. 36982475 1 41 theme adult 159:163 arg1 population 165:174 world's adult population 151:174 world's adult population 151:174 Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. 36982475 0 42 theme Urinary 26:32 arg1 Peptidome 34:42 Urinary Peptidome 26:42 Urinary Peptidome 26:42 Glycosylation Analysis of Urinary Peptidome Highlights IGF2 Glycopeptides in Association with CKD. 36982475 6 43 gly glycopeptides 768:780 arg2 glycopeptides 768:780 17 O-linked glycopeptides 756:780 17 O-linked glycopeptides from 7 different proteins 756:806 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 6 43 gly glycopeptides 768:780 arg1 proteins 799:806 7 different proteins 787:806 7 different proteins 787:806 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 3 44 gly glycopeptides 326:338 arg2 glycopeptides 326:338 urinary O-linked glycopeptides 309:338 urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations 309:420 The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. 36982475 1 45 theme kidney 107:112 arg1 CKD 123:125 CKD 123:125 CKD 123:125 Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. 36982475 1 45 theme kidney 107:112 arg1 disease 114:120 Chronic kidney disease 99:120 Chronic kidney disease (CKD) 99:126 Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. 36982475 1 46 theme population 165:174 arg1 population 165:174 world's adult population 151:174 world's adult population 151:174 Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. 36982475 1 46 theme population 165:174 arg1 % 146:146 10% 144:146 10% of world's adult population 144:174 Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. 36982475 4 47 theme specific 542:549 arg1 software 551:558 a specific software 540:558 a specific software followed by manual inspection of the spectra 540:603 Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the spectra. 36982475 6 48 theme growth 861:866 arg1 IGF2 879:882 IGF2 879:882 IGF2 879:882 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 6 48 theme growth 861:866 arg1 factor-II 868:876 Insulin-like growth factor-II 848:876 Insulin-like growth factor-II (IGF2) 848:883 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 9 49 theme strong 1136:1141 arg1 association 1152:1162 a strong negative association 1134:1162 a strong negative association with eGFR 1134:1172 The IGF2 glycopeptide (tPPTVLPDNFPRYP) showed a strong negative association with eGFR. 36982475 8 50 dep glycopeptides 966:978 arg1 DVStPPTVLPDNFPRYPVG 1004:1022 DVStPPTVLPDNFPRYPVG 1004:1022 DVStPPTVLPDNFPRYPVG 1004:1022 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. 36982475 8 50 dep glycopeptides 966:978 arg1 DVStPPTVLPDNFPRYPVGKF 981:1001 DVStPPTVLPDNFPRYPVGKF 981:1001 DVStPPTVLPDNFPRYPVGKF 981:1001 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. 36982475 8 50 dep glycopeptides 966:978 arg1 glycopeptides 966:978 Three glycopeptides 960:978 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) 960:1045 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. 36982475 8 50 dep glycopeptides 966:978 arg1 DVStPPTVLPDNFPRYP 1028:1044 DVStPPTVLPDNFPRYP 1028:1044 DVStPPTVLPDNFPRYP 1028:1044 Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. 36982475 2 51 gly glycosylation 197:209 arg1 progression 239:249 CKD progression 235:249 CKD progression 235:249 The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. 36982475 4 52 theme Urine 423:427 arg1 samples 429:435 Urine samples 423:435 Urine samples from eight CKD and two healthy subjects 423:475 Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the spectra. 36982475 3 53 theme molecular 397:405 arg1 manifestations 407:420 CKD molecular manifestations 393:420 CKD molecular manifestations 393:420 The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. 36982475 0 54 theme Peptidome 34:42 arg1 Analysis 14:21 Glycosylation Analysis 0:21 Glycosylation Analysis of Urinary Peptidome 0:42 Glycosylation Analysis of Urinary Peptidome Highlights IGF2 Glycopeptides in Association with CKD. 36982475 11 55 theme increased 1399:1407 arg1 levels 1416:1421 IGF2 increased plasma levels 1394:1421 IGF2 increased plasma levels 1394:1421 Further experiments corroborated this hypothesis as IGF2 increased plasma levels were observed in CKD patients. 36982475 2 56 theme glycosylation 197:209 arg1 unknown 262:268 unknown 262:268 unknown 262:268 The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. 36982475 2 56 theme glycosylation 197:209 arg1 role 181:184 The role 177:184 The role of protein glycosylation in causal mechanisms of CKD progression 177:249 The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. 36982475 9 57 theme negative 1143:1150 arg1 association 1152:1162 a strong negative association 1134:1162 a strong negative association with eGFR 1134:1172 The IGF2 glycopeptide (tPPTVLPDNFPRYP) showed a strong negative association with eGFR. 36982475 5 58 theme existing 727:734 arg1 datasets 736:743 3810 existing datasets 722:743 3810 existing datasets 722:743 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 11 59 theme IGF2 1394:1397 arg1 levels 1416:1421 IGF2 increased plasma levels 1394:1421 IGF2 increased plasma levels 1394:1421 Further experiments corroborated this hypothesis as IGF2 increased plasma levels were observed in CKD patients. 36982475 10 60 theme mature 1321:1326 arg1 protein 1333:1339 mature IGF2 protein 1321:1339 mature IGF2 protein 1321:1339 These results suggest that with aging and deteriorating kidney function, alterations in IGF2 proteoforms take place, which may reflect changes in mature IGF2 protein. 36982475 3 61 from glycopeptides 326:338 arg1 association 343:353 association 343:353 association to CKD 343:360 The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. 36982475 2 62 theme protein 189:195 arg1 glycosylation 197:209 protein glycosylation 189:209 protein glycosylation 189:209 The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. 36982475 5 63 gly glycopeptides 637:649 arg2 glycopeptides 637:649 the identified glycopeptides 622:649 the identified glycopeptides 622:649 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 0 64 theme IGF2 55:58 arg1 Glycopeptides 60:72 IGF2 Glycopeptides 55:72 IGF2 Glycopeptides 55:72 Glycosylation Analysis of Urinary Peptidome Highlights IGF2 Glycopeptides in Association with CKD. 36982475 9 65 gly glycopeptide 1097:1108 arg2 tPPTVLPDNFPRYP 1111:1124 tPPTVLPDNFPRYP 1111:1124 tPPTVLPDNFPRYP 1111:1124 The IGF2 glycopeptide (tPPTVLPDNFPRYP) showed a strong negative association with eGFR. 36982475 9 65 gly glycopeptide 1097:1108 arg2 glycopeptide 1097:1108 The IGF2 glycopeptide 1088:1108 The IGF2 glycopeptide (tPPTVLPDNFPRYP) 1088:1125 The IGF2 glycopeptide (tPPTVLPDNFPRYP) showed a strong negative association with eGFR. 36982475 10 66 from changes 1310:1316 arg1 protein 1333:1339 mature IGF2 protein 1321:1339 mature IGF2 protein 1321:1339 These results suggest that with aging and deteriorating kidney function, alterations in IGF2 proteoforms take place, which may reflect changes in mature IGF2 protein. 36982475 12 67 theme cathepsin 1547:1555 arg1 S 1557:1557 cathepsin S 1547:1557 cathepsin S 1547:1557 Protease predictions, considering also available transcriptomics data, suggest activation of cathepsin S with CKD, meriting further investigation. 36982475 11 68 located observed 1428:1435 arg1 patients 1444:1451 CKD patients 1440:1451 CKD patients 1440:1451 Further experiments corroborated this hypothesis as IGF2 increased plasma levels were observed in CKD patients. 36982475 11 68 located observed 1428:1435 arg2 levels 1416:1421 IGF2 increased plasma levels 1394:1421 IGF2 increased plasma levels 1394:1421 Further experiments corroborated this hypothesis as IGF2 increased plasma levels were observed in CKD patients. 36982475 2 69 theme CKD 235:237 arg1 progression 239:249 CKD progression 235:249 CKD progression 235:249 The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. 36982475 6 70 theme different 789:797 arg1 proteins 799:806 7 different proteins 787:806 7 different proteins 787:806 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 12 71 theme transcriptomics 1503:1517 arg1 data 1519:1522 available transcriptomics data 1493:1522 available transcriptomics data 1493:1522 Protease predictions, considering also available transcriptomics data, suggest activation of cathepsin S with CKD, meriting further investigation. 36982475 10 72 theme IGF2 1263:1266 arg1 proteoforms 1268:1278 IGF2 proteoforms 1263:1278 IGF2 proteoforms 1263:1278 These results suggest that with aging and deteriorating kidney function, alterations in IGF2 proteoforms take place, which may reflect changes in mature IGF2 protein. 36982475 10 73 from alterations 1248:1258 arg1 proteoforms 1268:1278 IGF2 proteoforms 1263:1278 IGF2 proteoforms 1263:1278 These results suggest that with aging and deteriorating kidney function, alterations in IGF2 proteoforms take place, which may reflect changes in mature IGF2 protein. 36982475 5 74 with Distribution 606:617 arg1 Age 678:680 Age 678:680 Age 678:680 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 5 74 with Distribution 606:617 arg1 Albuminuria 692:702 Albuminuria 692:702 Albuminuria 692:702 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 5 74 with Distribution 606:617 arg1 eGFR 683:686 eGFR 683:686 eGFR 683:686 Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. 36982475 6 75 theme Insulin-like 848:859 arg1 IGF2 879:882 IGF2 879:882 IGF2 879:882 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 6 75 theme Insulin-like 848:859 arg1 factor-II 868:876 Insulin-like growth factor-II 848:876 Insulin-like growth factor-II (IGF2) 848:883 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 6 76 link O-linked 759:766 arg1 glycopeptides 768:780 17 O-linked glycopeptides 756:780 17 O-linked glycopeptides from 7 different proteins 756:806 In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). 36982475 12 77 theme further 1578:1584 arg1 investigation 1586:1598 further investigation 1578:1598 further investigation 1578:1598 Protease predictions, considering also available transcriptomics data, suggest activation of cathepsin S with CKD, meriting further investigation. 36982475 4 78 theme spectra 597:603 arg1 inspection 579:588 manual inspection 572:588 manual inspection of the spectra 572:603 Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the spectra. 36982475 10 79 theme kidney 1231:1236 arg1 function 1238:1245 deteriorating kidney function 1217:1245 deteriorating kidney function 1217:1245 These results suggest that with aging and deteriorating kidney function, alterations in IGF2 proteoforms take place, which may reflect changes in mature IGF2 protein. 36982475 1 80 from prevalent 131:139 arg1 population 165:174 world's adult population 151:174 world's adult population 151:174 Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. 36982475 1 80 from prevalent 131:139 arg1 % 146:146 10% 144:146 10% of world's adult population 144:174 Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. 36982475 2 81 theme causal 214:219 arg1 mechanisms 221:230 causal mechanisms 214:230 causal mechanisms of CKD progression 214:249 The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. 36982475 4 82 gly glycopeptides 507:519 arg2 glycopeptides 507:519 glycopeptides 507:519 glycopeptides 507:519 Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the spectra. 34921405 5 0 from content 710:716 arg1 media 685:689 standard media 676:689 standard media 676:689 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 12 1 dep CONCLUSIONS 1482:1492 arg1 provide 1505:1511 provide 1505:1511 provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product 1505:1637 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 5 2 theme 0.29 mmol L-1 572:584 arg1 Se 586:587 0.29 mmol L-1 Se 572:587 0.29 mmol L-1 Se 572:587 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 11 3 theme crude 1448:1452 arg1 fat 1454:1456 crude fat 1448:1456 crude fat 1448:1456 By contrast, Se-enriched I. hispidus mycelium was of higher quality due to reduction in crude fat and total ash contents. 34921405 8 4 theme conidial 1069:1076 arg1 production 1078:1087 conidial production 1069:1087 conidial production in I. hispidus 1069:1102 However, conidial production in I. hispidus increased dramatically. 34921405 6 5 theme morphological 782:794 arg1 features 796:803 morphological features 782:803 morphological features of I. hispidus 782:818 The influence of Se accumulation on morphological features of I. hispidus were examined by microscopic and scanning electron microscopic observation. 34921405 4 6 theme % 507:507 arg1 inhibition 516:525 50% growth inhibition 505:525 50% growth inhibition 505:525 RESULTS Inonotus hispidus was capable of tolerating up to 3.85 mmol L-1 selenite, at which ~85% growth inhibition was seen, with 50% growth inhibition occurring at ~1 mmol L-1 selenite. 34921405 7 7 theme connections 1024:1034 arg1 collapse 1006:1013 collapse 1006:1013 collapse 1006:1013 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 7 7 theme connections 1024:1034 arg1 branching 992:1000 decreased branching 982:1000 decreased branching 982:1000 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 10 8 theme selenocompounds 1293:1307 arg1 yield 1270:1274 the yield 1266:1274 the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides 1266:1357 Se accumulation had only minimal impacts on the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides. 34921405 4 9 dep RESULTS 376:382 arg1 capable 406:412 capable 406:412 capable 406:412 RESULTS Inonotus hispidus was capable of tolerating up to 3.85 mmol L-1 selenite, at which ~85% growth inhibition was seen, with 50% growth inhibition occurring at ~1 mmol L-1 selenite. 34921405 6 10 theme accumulation 766:777 arg1 influence 750:758 The influence 746:758 The influence of Se accumulation on morphological features of I. hispidus 746:818 The influence of Se accumulation on morphological features of I. hispidus were examined by microscopic and scanning electron microscopic observation. 34921405 11 11 theme ash 1468:1470 arg1 contents 1472:1479 total ash contents 1462:1479 total ash contents 1462:1479 By contrast, Se-enriched I. hispidus mycelium was of higher quality due to reduction in crude fat and total ash contents. 34921405 5 12 theme I. 601:602 arg1 mycelium 613:620 I. hispidus mycelium 601:620 I. hispidus mycelium with 115 times higher Se levels 601:652 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 13 13 theme Chemical 1658:1665 arg1 Industry 1667:1674 Chemical Industry 1658:1674 Chemical Industry 1658:1674 © 2021 Society of Chemical Industry. 34921405 7 14 theme higher 1042:1047 arg1 stress 1052:1057 higher Se stress 1042:1057 higher Se stress 1042:1057 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 6 15 theme scanning 853:860 arg1 observation 883:893 microscopic and scanning electron microscopic observation 837:893 observation 883:893 The influence of Se accumulation on morphological features of I. hispidus were examined by microscopic and scanning electron microscopic observation. 34921405 7 16 theme decreased 982:990 arg1 branching 992:1000 decreased branching 982:1000 decreased branching 982:1000 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 9 17 theme Se 1145:1146 arg1 influence 1132:1140 The influence 1128:1140 The influence of Se on mycelial growth 1128:1165 The influence of Se on mycelial growth could be recovered by reinoculation in standard media. 34921405 6 18 theme microscopic 837:847 arg1 observation 883:893 microscopic and scanning electron microscopic observation 837:893 observation 883:893 The influence of Se accumulation on morphological features of I. hispidus were examined by microscopic and scanning electron microscopic observation. 34921405 12 19 theme better 1616:1621 arg1 hispidus 1588:1595 selenized I. hispidus 1575:1595 selenized I. hispidus 1575:1595 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 12 19 theme better 1616:1621 arg1 product 1631:1637 an enriched and better quality product 1600:1637 an enriched and better quality product 1600:1637 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 5 20 theme higher 637:642 arg1 levels 647:652 115 times higher Se levels 627:652 115 times higher Se levels 627:652 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 9 21 theme mycelial 1151:1158 arg1 growth 1160:1165 mycelial growth 1151:1165 mycelial growth 1151:1165 The influence of Se on mycelial growth could be recovered by reinoculation in standard media. 34921405 7 22 theme significant 916:926 arg1 shrinkage 928:936 significant shrinkage 916:936 significant shrinkage 916:936 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 5 23 theme Se 734:735 arg1 content 737:743 total Se content 728:743 total Se content 728:743 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 9 24 from influence 1132:1140 arg1 growth 1160:1165 mycelial growth 1151:1165 mycelial growth 1151:1165 The influence of Se on mycelial growth could be recovered by reinoculation in standard media. 34921405 7 25 theme I. 958:959 arg1 hyphae 970:975 I. hispidus hyphae 958:975 I. hispidus hyphae 958:975 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 2 26 from Se 235:236 arg1 form 249:252 organic form 241:252 organic form 241:252 Many fungi have effective mechanisms to acquire, transform and accumulate Se in organic form. 34921405 6 27 theme hispidus 811:818 arg1 features 796:803 morphological features 782:803 morphological features of I. hispidus 782:818 The influence of Se accumulation on morphological features of I. hispidus were examined by microscopic and scanning electron microscopic observation. 34921405 5 28 from growth 666:671 arg1 media 685:689 standard media 676:689 standard media 676:689 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 0 29 theme shaggy 44:49 arg1 fungus 59:64 the shaggy bracket fungus 40:64 the shaggy bracket fungus 40:64 Influence of selenium on the mycelia of the shaggy bracket fungus, Inonotus hispidus. 34921405 0 29 theme shaggy 44:49 arg1 hispidus 76:83 Inonotus hispidus 67:83 Inonotus hispidus 67:83 Influence of selenium on the mycelia of the shaggy bracket fungus, Inonotus hispidus. 34921405 0 30 theme fungus 59:64 arg1 mycelia 29:35 the mycelia 25:35 the mycelia of the shaggy bracket fungus, Inonotus hispidus 25:83 Influence of selenium on the mycelia of the shaggy bracket fungus, Inonotus hispidus. 34921405 9 31 theme standard 1206:1213 arg1 media 1215:1219 standard media 1206:1219 standard media 1206:1219 The influence of Se on mycelial growth could be recovered by reinoculation in standard media. 34921405 1 32 theme trace 123:127 arg1 element 129:135 a needed trace element 114:135 a needed trace element for animals and humans 114:158 BACKGROUND Selenium (Se) is a needed trace element for animals and humans. 34921405 1 32 theme trace 123:127 arg1 Selenium 97:104 BACKGROUND Selenium 86:104 BACKGROUND Selenium (Se) 86:109 BACKGROUND Selenium (Se) is a needed trace element for animals and humans. 34921405 12 33 theme enriched 1603:1610 arg1 hispidus 1588:1595 selenized I. hispidus 1575:1595 selenized I. hispidus 1575:1595 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 12 33 theme enriched 1603:1610 arg1 product 1631:1637 an enriched and better quality product 1600:1637 an enriched and better quality product 1600:1637 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 3 34 theme Se 295:296 arg1 effects 274:280 the effects 270:280 the effects of inorganic Se (sodium selenite) on the medicinal fungus Inonotus hispidus 270:356 In this study, the effects of inorganic Se (sodium selenite) on the medicinal fungus Inonotus hispidus was investigated. 34921405 0 35 from Influence 0:8 arg1 mycelia 29:35 the mycelia 25:35 the mycelia of the shaggy bracket fungus, Inonotus hispidus 25:83 Influence of selenium on the mycelia of the shaggy bracket fungus, Inonotus hispidus. 34921405 0 36 theme Inonotus 67:74 arg1 fungus 59:64 the shaggy bracket fungus 40:64 the shaggy bracket fungus 40:64 Influence of selenium on the mycelia of the shaggy bracket fungus, Inonotus hispidus. 34921405 0 36 theme Inonotus 67:74 arg1 hispidus 76:83 Inonotus hispidus 67:83 Inonotus hispidus 67:83 Influence of selenium on the mycelia of the shaggy bracket fungus, Inonotus hispidus. 34921405 6 37 theme microscopic 871:881 arg1 observation 883:893 microscopic and scanning electron microscopic observation 837:893 observation 883:893 The influence of Se accumulation on morphological features of I. hispidus were examined by microscopic and scanning electron microscopic observation. 34921405 12 38 theme I. 1585:1586 arg1 hispidus 1588:1595 selenized I. hispidus 1575:1595 selenized I. hispidus 1575:1595 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 12 38 theme I. 1585:1586 arg1 product 1631:1637 an enriched and better quality product 1600:1637 an enriched and better quality product 1600:1637 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 5 39 with mycelium 613:620 arg1 levels 647:652 115 times higher Se levels 627:652 115 times higher Se levels 627:652 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 0 40 dep fungus 59:64 arg1 bracket 51:57 bracket 51:57 bracket 51:57 Influence of selenium on the mycelia of the shaggy bracket fungus, Inonotus hispidus. 34921405 3 41 theme sodium 299:304 arg1 Se 295:296 inorganic Se 285:296 inorganic Se (sodium selenite) 285:314 In this study, the effects of inorganic Se (sodium selenite) on the medicinal fungus Inonotus hispidus was investigated. 34921405 3 41 theme sodium 299:304 arg1 selenite 306:313 sodium selenite 299:313 sodium selenite 299:313 In this study, the effects of inorganic Se (sodium selenite) on the medicinal fungus Inonotus hispidus was investigated. 34921405 4 42 theme growth 472:477 arg1 inhibition 479:488 ~85% growth inhibition 467:488 ~85% growth inhibition 467:488 RESULTS Inonotus hispidus was capable of tolerating up to 3.85 mmol L-1 selenite, at which ~85% growth inhibition was seen, with 50% growth inhibition occurring at ~1 mmol L-1 selenite. 34921405 11 43 theme I. 1385:1386 arg1 mycelium 1397:1404 Se-enriched I. hispidus mycelium 1373:1404 Se-enriched I. hispidus mycelium 1373:1404 By contrast, Se-enriched I. hispidus mycelium was of higher quality due to reduction in crude fat and total ash contents. 34921405 0 44 theme selenium 13:20 arg1 Influence 0:8 Influence 0:8 Influence of selenium on the mycelia of the shaggy bracket fungus, Inonotus hispidus. 0:84 Influence of selenium on the mycelia of the shaggy bracket fungus, Inonotus hispidus. 34921405 1 45 theme BACKGROUND 86:95 arg1 Se 107:108 Se 107:108 Se 107:108 BACKGROUND Selenium (Se) is a needed trace element for animals and humans. 34921405 1 45 theme BACKGROUND 86:95 arg1 Selenium 97:104 BACKGROUND Selenium 86:104 BACKGROUND Selenium (Se) 86:109 BACKGROUND Selenium (Se) is a needed trace element for animals and humans. 34921405 1 45 theme BACKGROUND 86:95 arg1 element 129:135 a needed trace element 114:135 a needed trace element for animals and humans 114:158 BACKGROUND Selenium (Se) is a needed trace element for animals and humans. 34921405 3 46 theme fungus 333:338 arg1 hispidus 349:356 the medicinal fungus Inonotus hispidus 319:356 the medicinal fungus Inonotus hispidus 319:356 In this study, the effects of inorganic Se (sodium selenite) on the medicinal fungus Inonotus hispidus was investigated. 34921405 5 47 theme organic 699:705 arg1 content 710:716 an organic Se content 696:716 an organic Se content of 86% to total Se content 696:743 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 4 48 dep 3.85 mmol L-1 434:446 arg1 to 431:432 to 431:432 to 431:432 RESULTS Inonotus hispidus was capable of tolerating up to 3.85 mmol L-1 selenite, at which ~85% growth inhibition was seen, with 50% growth inhibition occurring at ~1 mmol L-1 selenite. 34921405 4 49 theme ~85 467:469 arg1 inhibition 479:488 ~85% growth inhibition 467:488 ~85% growth inhibition 467:488 RESULTS Inonotus hispidus was capable of tolerating up to 3.85 mmol L-1 selenite, at which ~85% growth inhibition was seen, with 50% growth inhibition occurring at ~1 mmol L-1 selenite. 34921405 2 50 theme Many 161:164 arg1 fungi 166:170 Many fungi 161:170 Many fungi 161:170 Many fungi have effective mechanisms to acquire, transform and accumulate Se in organic form. 34921405 2 51 contain have 172:175 arg2 mechanisms 187:196 effective mechanisms 177:196 effective mechanisms to acquire, transform and accumulate Se in organic form 177:252 Many fungi have effective mechanisms to acquire, transform and accumulate Se in organic form. 34921405 2 51 contain have 172:175 arg1 fungi 166:170 Many fungi 161:170 Many fungi 161:170 Many fungi have effective mechanisms to acquire, transform and accumulate Se in organic form. 34921405 4 52 theme growth 509:514 arg1 inhibition 516:525 50% growth inhibition 505:525 50% growth inhibition 505:525 RESULTS Inonotus hispidus was capable of tolerating up to 3.85 mmol L-1 selenite, at which ~85% growth inhibition was seen, with 50% growth inhibition occurring at ~1 mmol L-1 selenite. 34921405 6 53 theme I. 808:809 arg1 hispidus 811:818 I. hispidus 808:818 I. hispidus 808:818 The influence of Se accumulation on morphological features of I. hispidus were examined by microscopic and scanning electron microscopic observation. 34921405 7 54 theme clamp 1018:1022 arg1 connections 1024:1034 clamp connections 1018:1034 clamp connections 1018:1034 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 2 55 theme organic 241:247 arg1 form 249:252 organic form 241:252 organic form 241:252 Many fungi have effective mechanisms to acquire, transform and accumulate Se in organic form. 34921405 4 56 theme 50 505:506 arg1 % 507:507 % 507:507 % 507:507 RESULTS Inonotus hispidus was capable of tolerating up to 3.85 mmol L-1 selenite, at which ~85% growth inhibition was seen, with 50% growth inhibition occurring at ~1 mmol L-1 selenite. 34921405 10 57 theme potential 1283:1291 arg1 acids 1323:1327 amino acids 1317:1327 amino acids 1317:1327 Se accumulation had only minimal impacts on the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides. 34921405 10 57 theme potential 1283:1291 arg1 polysaccharides 1343:1357 polysaccharides 1343:1357 polysaccharides 1343:1357 Se accumulation had only minimal impacts on the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides. 34921405 10 57 theme potential 1283:1291 arg1 selenocompounds 1293:1307 the potential selenocompounds 1279:1307 the potential selenocompounds such as amino acids, proteins and polysaccharides 1279:1357 Se accumulation had only minimal impacts on the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides. 34921405 10 57 theme potential 1283:1291 arg1 proteins 1330:1337 proteins 1330:1337 proteins 1330:1337 Se accumulation had only minimal impacts on the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides. 34921405 3 58 theme medicinal 323:331 arg1 hispidus 349:356 the medicinal fungus Inonotus hispidus 319:356 the medicinal fungus Inonotus hispidus 319:356 In this study, the effects of inorganic Se (sodium selenite) on the medicinal fungus Inonotus hispidus was investigated. 34921405 6 59 theme Se 763:764 arg1 accumulation 766:777 Se accumulation 763:777 Se accumulation 763:777 The influence of Se accumulation on morphological features of I. hispidus were examined by microscopic and scanning electron microscopic observation. 34921405 12 60 theme basic 1513:1517 arg1 information 1531:1541 basic and applied information 1513:1541 basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product 1513:1637 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 8 61 theme I. 1092:1093 arg1 hispidus 1095:1102 I. hispidus 1092:1102 I. hispidus 1092:1102 However, conidial production in I. hispidus increased dramatically. 34921405 6 62 theme electron 862:869 arg1 observation 883:893 microscopic and scanning electron microscopic observation 837:893 observation 883:893 The influence of Se accumulation on morphological features of I. hispidus were examined by microscopic and scanning electron microscopic observation. 34921405 6 63 from influence 750:758 arg1 features 796:803 morphological features 782:803 morphological features of I. hispidus 782:818 The influence of Se accumulation on morphological features of I. hispidus were examined by microscopic and scanning electron microscopic observation. 34921405 10 64 theme amino 1317:1321 arg1 acids 1323:1327 amino acids 1317:1327 amino acids 1317:1327 Se accumulation had only minimal impacts on the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides. 34921405 5 65 theme % 723:723 arg1 content 710:716 an organic Se content 696:716 an organic Se content of 86% to total Se content 696:743 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 5 65 theme % 723:723 arg1 growth 666:671 growth 666:671 growth in standard media 666:689 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 12 66 theme applied 1523:1529 arg1 information 1531:1541 basic and applied information 1513:1541 basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product 1513:1637 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 4 67 theme Inonotus 384:391 arg1 hispidus 393:400 Inonotus hispidus 384:400 Inonotus hispidus 384:400 RESULTS Inonotus hispidus was capable of tolerating up to 3.85 mmol L-1 selenite, at which ~85% growth inhibition was seen, with 50% growth inhibition occurring at ~1 mmol L-1 selenite. 34921405 12 68 from information 1531:1541 arg1 feasibility 1550:1560 the feasibility 1546:1560 the feasibility of producing selenized I. hispidus as an enriched and better quality product 1546:1637 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 4 69 theme ~1 mmol L-1 540:550 arg1 selenite 552:559 ~1 mmol L-1 selenite 540:559 ~1 mmol L-1 selenite 540:559 RESULTS Inonotus hispidus was capable of tolerating up to 3.85 mmol L-1 selenite, at which ~85% growth inhibition was seen, with 50% growth inhibition occurring at ~1 mmol L-1 selenite. 34921405 7 70 theme hispidus 961:968 arg1 hyphae 970:975 I. hispidus hyphae 958:975 I. hispidus hyphae 958:975 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 5 71 theme total 728:732 arg1 content 737:743 total Se content 728:743 total Se content 728:743 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 2 72 theme effective 177:185 arg1 mechanisms 187:196 effective mechanisms 177:196 effective mechanisms to acquire, transform and accumulate Se in organic form 177:252 Many fungi have effective mechanisms to acquire, transform and accumulate Se in organic form. 34921405 11 73 theme total 1462:1466 arg1 contents 1472:1479 total ash contents 1462:1479 total ash contents 1462:1479 By contrast, Se-enriched I. hispidus mycelium was of higher quality due to reduction in crude fat and total ash contents. 34921405 5 74 theme hispidus 604:611 arg1 mycelium 613:620 I. hispidus mycelium 601:620 I. hispidus mycelium with 115 times higher Se levels 601:652 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 11 75 theme hispidus 1388:1395 arg1 mycelium 1397:1404 Se-enriched I. hispidus mycelium 1373:1404 Se-enriched I. hispidus mycelium 1373:1404 By contrast, Se-enriched I. hispidus mycelium was of higher quality due to reduction in crude fat and total ash contents. 34921405 3 76 from effects 274:280 arg1 hispidus 349:356 the medicinal fungus Inonotus hispidus 319:356 the medicinal fungus Inonotus hispidus 319:356 In this study, the effects of inorganic Se (sodium selenite) on the medicinal fungus Inonotus hispidus was investigated. 34921405 11 77 from reduction 1435:1443 arg1 fat 1454:1456 crude fat 1448:1456 crude fat 1448:1456 By contrast, Se-enriched I. hispidus mycelium was of higher quality due to reduction in crude fat and total ash contents. 34921405 11 77 from reduction 1435:1443 arg1 contents 1472:1479 total ash contents 1462:1479 total ash contents 1462:1479 By contrast, Se-enriched I. hispidus mycelium was of higher quality due to reduction in crude fat and total ash contents. 34921405 12 78 theme quality 1623:1629 arg1 hispidus 1588:1595 selenized I. hispidus 1575:1595 selenized I. hispidus 1575:1595 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 12 78 theme quality 1623:1629 arg1 product 1631:1637 an enriched and better quality product 1600:1637 an enriched and better quality product 1600:1637 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 5 79 theme standard 676:683 arg1 media 685:689 standard media 676:689 standard media 676:689 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 1 80 theme needed 116:121 arg1 element 129:135 a needed trace element 114:135 a needed trace element for animals and humans 114:158 BACKGROUND Selenium (Se) is a needed trace element for animals and humans. 34921405 1 80 theme needed 116:121 arg1 Selenium 97:104 BACKGROUND Selenium 86:104 BACKGROUND Selenium (Se) 86:109 BACKGROUND Selenium (Se) is a needed trace element for animals and humans. 34921405 11 81 theme higher 1413:1418 arg1 quality 1420:1426 higher quality 1413:1426 higher quality 1413:1426 By contrast, Se-enriched I. hispidus mycelium was of higher quality due to reduction in crude fat and total ash contents. 34921405 5 82 theme Se 644:645 arg1 levels 647:652 115 times higher Se levels 627:652 115 times higher Se levels 627:652 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 3 83 theme inorganic 285:293 arg1 Se 295:296 inorganic Se 285:296 inorganic Se (sodium selenite) 285:314 In this study, the effects of inorganic Se (sodium selenite) on the medicinal fungus Inonotus hispidus was investigated. 34921405 3 83 theme inorganic 285:293 arg1 selenite 306:313 sodium selenite 299:313 sodium selenite 299:313 In this study, the effects of inorganic Se (sodium selenite) on the medicinal fungus Inonotus hispidus was investigated. 34921405 5 84 theme Se 707:708 arg1 content 710:716 an organic Se content 696:716 an organic Se content of 86% to total Se content 696:743 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 10 85 contain had 1238:1240 arg1 accumulation 1225:1236 Se accumulation 1222:1236 Se accumulation 1222:1236 Se accumulation had only minimal impacts on the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides. 34921405 10 85 contain had 1238:1240 arg2 impacts 1255:1261 only minimal impacts 1242:1261 only minimal impacts 1242:1261 Se accumulation had only minimal impacts on the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides. 34921405 12 86 theme selenized 1575:1583 arg1 hispidus 1588:1595 selenized I. hispidus 1575:1595 selenized I. hispidus 1575:1595 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 12 86 theme selenized 1575:1583 arg1 product 1631:1637 an enriched and better quality product 1600:1637 an enriched and better quality product 1600:1637 CONCLUSIONS These data provide basic and applied information on the feasibility of producing selenized I. hispidus as an enriched and better quality product. 34921405 5 87 dep resulted 589:596 arg1 compared 654:661 compared 654:661 compared to growth in standard media, and an organic Se content of 86% to total Se content 654:743 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 11 88 theme Se-enriched 1373:1383 arg1 mycelium 1397:1404 Se-enriched I. hispidus mycelium 1373:1404 Se-enriched I. hispidus mycelium 1373:1404 By contrast, Se-enriched I. hispidus mycelium was of higher quality due to reduction in crude fat and total ash contents. 34921405 5 89 from Growth 562:567 arg1 Se 586:587 0.29 mmol L-1 Se 572:587 0.29 mmol L-1 Se 572:587 Growth in 0.29 mmol L-1 Se resulted in I. hispidus mycelium with 115 times higher Se levels compared to growth in standard media, and an organic Se content of 86% to total Se content. 34921405 10 90 theme Se 1222:1223 arg1 accumulation 1225:1236 Se accumulation 1222:1236 Se accumulation 1222:1236 Se accumulation had only minimal impacts on the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides. 34921405 3 91 theme Inonotus 340:347 arg1 hispidus 349:356 the medicinal fungus Inonotus hispidus 319:356 the medicinal fungus Inonotus hispidus 319:356 In this study, the effects of inorganic Se (sodium selenite) on the medicinal fungus Inonotus hispidus was investigated. 34921405 7 92 theme Se 1049:1050 arg1 stress 1052:1057 higher Se stress 1042:1057 higher Se stress 1042:1057 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 7 93 theme hyphae 970:975 arg1 deformations 942:953 deformations 942:953 deformations of I. hispidus hyphae 942:975 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 7 93 theme hyphae 970:975 arg1 shrinkage 928:936 significant shrinkage 916:936 significant shrinkage 916:936 These data revealed significant shrinkage and deformations of I. hispidus hyphae with decreased branching and collapse of clamp connections under higher Se stress. 34921405 4 94 theme % 470:470 arg1 inhibition 479:488 ~85% growth inhibition 467:488 ~85% growth inhibition 467:488 RESULTS Inonotus hispidus was capable of tolerating up to 3.85 mmol L-1 selenite, at which ~85% growth inhibition was seen, with 50% growth inhibition occurring at ~1 mmol L-1 selenite. 34921405 10 95 theme minimal 1247:1253 arg1 impacts 1255:1261 only minimal impacts 1242:1261 only minimal impacts 1242:1261 Se accumulation had only minimal impacts on the yield of the potential selenocompounds such as amino acids, proteins and polysaccharides. 34921405 8 96 from production 1078:1087 arg1 hispidus 1095:1102 I. hispidus 1092:1102 I. hispidus 1092:1102 However, conidial production in I. hispidus increased dramatically. 37303063 0 0 theme multiple 72:79 arg1 levels 81:86 multiple levels 72:86 multiple levels in lung adenocarcinoma 72:109 B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma. 37303063 2 1 theme early-stage 466:476 arg1 diagnosis 483:491 early-stage LUAD diagnosis 466:491 early-stage LUAD diagnosis 466:491 Identifying the molecular events underlying the progression from MIA to IAC may provide a crucial perspective and boost the exploration of novel strategies for early-stage LUAD diagnosis and treatment. 37303063 11 2 theme LUAD 1770:1773 arg1 intervention 1775:1786 LUAD intervention 1770:1786 LUAD intervention 1770:1786 CONCLUSION B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy. 37303063 7 3 theme N-linked 1234:1241 arg1 glycosylation 1243:1255 the N-linked glycosylation 1230:1255 the N-linked glycosylation of PD-L1 protein 1230:1272 Mechanistically, B4GALT1 directly mediates the N-linked glycosylation of PD-L1 protein, thus preventing PD-L1 degradation at the posttranscriptional level. 37303063 10 4 theme B4GALT1 1538:1544 arg1 inhibition 1524:1533 inhibition 1524:1533 inhibition of B4GALT1 1524:1544 Importantly, inhibition of B4GALT1 increased CD8 + T-cell abundance and activity and enhanced the antitumour immunity of anti-PD-1 therapy in vivo. 37303063 11 5 theme CONCLUSION 1659:1668 arg1 molecule 1692:1699 a critical molecule 1681:1699 a critical molecule 1681:1699 CONCLUSION B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy. 37303063 11 5 theme CONCLUSION 1659:1668 arg1 B4GALT1 1670:1676 CONCLUSION B4GALT1 1659:1676 CONCLUSION B4GALT1 1659:1676 CONCLUSION B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy. 37303063 9 6 theme immune 1496:1501 arg1 escape 1503:1508 lung cancer immune escape 1484:1508 lung cancer immune escape 1484:1508 These factors lead to lung cancer immune escape. 37303063 9 7 theme lung 1484:1487 arg1 escape 1503:1508 lung cancer immune escape 1484:1508 lung cancer immune escape 1484:1508 These factors lead to lung cancer immune escape. 37303063 4 8 theme evasion 840:846 arg1 mechanism 803:811 the regulatory mechanism 788:811 the regulatory mechanism of B4GALT1-mediated immune evasion 788:846 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 6 9 theme CD8 + T 1172:1178 arg1 cells 1180:1184 CD8 + T cells 1172:1184 CD8 + T cells 1172:1184 Further experiments revealed that B4GALT1 regulated LUAD cell proliferation and invasion both in vitro and in vivo and was related to the impaired antitumour capacity of CD8 + T cells. 37303063 5 10 theme N-glycan 942:949 arg1 biosynthesis 951:962 N-glycan biosynthesis 942:962 N-glycan biosynthesis 942:962 RESULTS B4GALT1, a key gene involved in N-glycan biosynthesis, was highly expressed in IAC samples. 37303063 1 11 theme dominant 233:240 arg1 subtype 255:261 the dominant pathological subtype 229:261 the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD) 229:303 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 1 11 theme dominant 233:240 arg1 adenocarcinoma 132:145 BACKGROUND Invasive adenocarcinoma 112:145 BACKGROUND Invasive adenocarcinoma (IAC) 112:151 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 6 12 theme impaired 1140:1147 arg1 capacity 1160:1167 the impaired antitumour capacity 1136:1167 the impaired antitumour capacity of CD8 + T cells 1136:1184 Further experiments revealed that B4GALT1 regulated LUAD cell proliferation and invasion both in vitro and in vivo and was related to the impaired antitumour capacity of CD8 + T cells. 37303063 1 13 theme pathological 242:253 arg1 subtype 255:261 the dominant pathological subtype 229:261 the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD) 229:303 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 1 13 theme pathological 242:253 arg1 adenocarcinoma 132:145 BACKGROUND Invasive adenocarcinoma 112:145 BACKGROUND Invasive adenocarcinoma (IAC) 112:151 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 4 14 dep in 754:755 arg1 vivo 757:760 vivo 757:760 vivo 757:760 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 3 15 theme Transcriptome 516:528 arg1 sequencing 530:539 METHODS Transcriptome sequencing 508:539 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients 508:633 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 0 16 theme lung 91:94 arg1 adenocarcinoma 96:109 lung adenocarcinoma 91:109 lung adenocarcinoma 91:109 B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma. 37303063 11 17 theme critical 1683:1690 arg1 molecule 1692:1699 a critical molecule 1681:1699 a critical molecule 1681:1699 CONCLUSION B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy. 37303063 11 17 theme critical 1683:1690 arg1 B4GALT1 1670:1676 CONCLUSION B4GALT1 1659:1676 CONCLUSION B4GALT1 1659:1676 CONCLUSION B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy. 37303063 6 18 theme antitumour 1149:1158 arg1 capacity 1160:1167 the impaired antitumour capacity 1136:1167 the impaired antitumour capacity of CD8 + T cells 1136:1184 Further experiments revealed that B4GALT1 regulated LUAD cell proliferation and invasion both in vitro and in vivo and was related to the impaired antitumour capacity of CD8 + T cells. 37303063 6 19 dep cell 1059:1062 arg1 proliferation 1064:1076 proliferation 1064:1076 proliferation 1064:1076 Further experiments revealed that B4GALT1 regulated LUAD cell proliferation and invasion both in vitro and in vivo and was related to the impaired antitumour capacity of CD8 + T cells. 37303063 10 20 theme anti-PD-1 1632:1640 arg1 therapy 1642:1648 anti-PD-1 therapy 1632:1648 anti-PD-1 therapy 1632:1648 Importantly, inhibition of B4GALT1 increased CD8 + T-cell abundance and activity and enhanced the antitumour immunity of anti-PD-1 therapy in vivo. 37303063 4 21 theme cell 873:876 arg1 death 878:882 programmed cell death ligand 1 (PD-L1) 862:899 programmed cell death ligand 1 (PD-L1) 862:899 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 7 22 theme PD-L1 1260:1264 arg1 protein 1266:1272 PD-L1 protein 1260:1272 PD-L1 protein 1260:1272 Mechanistically, B4GALT1 directly mediates the N-linked glycosylation of PD-L1 protein, thus preventing PD-L1 degradation at the posttranscriptional level. 37303063 3 23 theme MIA 558:560 arg1 tumours 570:576 IAC tumours 566:576 IAC tumours obtained from four multiple primary lung cancer patients 566:633 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 3 23 theme MIA 558:560 arg1 pairs 549:553 four pairs 544:553 four pairs of MIA 544:560 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 7 24 theme posttranscriptional 1316:1334 arg1 level 1336:1340 the posttranscriptional level 1312:1340 the posttranscriptional level 1312:1340 Mechanistically, B4GALT1 directly mediates the N-linked glycosylation of PD-L1 protein, thus preventing PD-L1 degradation at the posttranscriptional level. 37303063 11 25 from molecule 1692:1699 arg1 development 1708:1718 the development 1704:1718 the development of early-stage LUAD 1704:1738 CONCLUSION B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy. 37303063 10 26 theme therapy 1642:1648 arg1 immunity 1620:1627 the antitumour immunity 1605:1627 the antitumour immunity of anti-PD-1 therapy 1605:1648 Importantly, inhibition of B4GALT1 increased CD8 + T-cell abundance and activity and enhanced the antitumour immunity of anti-PD-1 therapy in vivo. 37303063 4 27 theme programmed 862:871 arg1 death 878:882 programmed cell death ligand 1 (PD-L1) 862:899 programmed cell death ligand 1 (PD-L1) 862:899 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 4 28 theme in 741:742 arg1 experiments 729:739 Function and mechanism experiments 706:739 Function and mechanism experiments in vitro and in vivo 706:760 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 11 29 theme LUAD 1735:1738 arg1 development 1708:1718 the development 1704:1718 the development of early-stage LUAD 1704:1738 CONCLUSION B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy. 37303063 8 30 theme transcriptional 1439:1453 arg1 level 1455:1459 the transcriptional level 1435:1459 the transcriptional level 1435:1459 In addition, B4GALT1 stabilized the TAZ protein via glycosylation, which activated CD274 at the transcriptional level. 37303063 7 31 link N-linked 1234:1241 arg1 glycosylation 1243:1255 the N-linked glycosylation 1230:1255 the N-linked glycosylation of PD-L1 protein 1230:1272 Mechanistically, B4GALT1 directly mediates the N-linked glycosylation of PD-L1 protein, thus preventing PD-L1 degradation at the posttranscriptional level. 37303063 4 32 theme immune 833:838 arg1 evasion 840:846 B4GALT1-mediated immune evasion 816:846 B4GALT1-mediated immune evasion 816:846 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 3 33 theme pairs 549:553 arg1 sequencing 530:539 METHODS Transcriptome sequencing 508:539 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients 508:633 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 2 34 theme crucial 396:402 arg1 perspective 404:414 a crucial perspective 394:414 a crucial perspective 394:414 Identifying the molecular events underlying the progression from MIA to IAC may provide a crucial perspective and boost the exploration of novel strategies for early-stage LUAD diagnosis and treatment. 37303063 0 35 theme immune 17:22 arg1 escape 24:29 immune escape 17:29 immune escape 17:29 B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma. 37303063 1 36 theme early-stage 266:276 arg1 LUAD 299:302 LUAD 299:302 LUAD 299:302 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 1 36 theme early-stage 266:276 arg1 adenocarcinoma 283:296 early-stage lung adenocarcinoma 266:296 early-stage lung adenocarcinoma (LUAD) 266:303 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 11 37 theme early-stage 1723:1733 arg1 LUAD 1735:1738 early-stage LUAD 1723:1738 early-stage LUAD 1723:1738 CONCLUSION B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy. 37303063 4 38 dep in 741:742 arg1 vitro 744:748 vitro 744:748 vitro 744:748 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 2 39 theme strategies 451:460 arg1 exploration 430:440 the exploration 426:440 the exploration of novel strategies for early-stage LUAD diagnosis and treatment 426:505 Identifying the molecular events underlying the progression from MIA to IAC may provide a crucial perspective and boost the exploration of novel strategies for early-stage LUAD diagnosis and treatment. 37303063 1 40 theme lung 278:281 arg1 LUAD 299:302 LUAD 299:302 LUAD 299:302 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 1 40 theme lung 278:281 arg1 adenocarcinoma 283:296 early-stage lung adenocarcinoma 266:296 early-stage lung adenocarcinoma (LUAD) 266:303 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 7 41 gly glycosylation 1243:1255 arg1 protein 1266:1272 PD-L1 protein 1260:1272 PD-L1 protein 1260:1272 Mechanistically, B4GALT1 directly mediates the N-linked glycosylation of PD-L1 protein, thus preventing PD-L1 degradation at the posttranscriptional level. 37303063 7 42 theme PD-L1 1291:1295 arg1 degradation 1297:1307 PD-L1 degradation 1291:1307 PD-L1 degradation 1291:1307 Mechanistically, B4GALT1 directly mediates the N-linked glycosylation of PD-L1 protein, thus preventing PD-L1 degradation at the posttranscriptional level. 37303063 4 43 theme B4GALT1-mediated 816:831 arg1 evasion 840:846 B4GALT1-mediated immune evasion 816:846 B4GALT1-mediated immune evasion 816:846 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 6 44 theme cells 1180:1184 arg1 capacity 1160:1167 the impaired antitumour capacity 1136:1167 the impaired antitumour capacity of CD8 + T cells 1136:1184 Further experiments revealed that B4GALT1 regulated LUAD cell proliferation and invasion both in vitro and in vivo and was related to the impaired antitumour capacity of CD8 + T cells. 37303063 1 45 theme invasive 195:202 arg1 MIA 220:222 MIA 220:222 MIA 220:222 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 1 45 theme invasive 195:202 arg1 adenocarcinoma 204:217 minimally invasive adenocarcinoma 185:217 minimally invasive adenocarcinoma (MIA) 185:223 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 2 46 theme novel 445:449 arg1 strategies 451:460 novel strategies 445:460 novel strategies for early-stage LUAD diagnosis and treatment 445:505 Identifying the molecular events underlying the progression from MIA to IAC may provide a crucial perspective and boost the exploration of novel strategies for early-stage LUAD diagnosis and treatment. 37303063 1 47 theme adenocarcinoma 283:296 arg1 subtype 255:261 the dominant pathological subtype 229:261 the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD) 229:303 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 1 47 theme adenocarcinoma 283:296 arg1 adenocarcinoma 132:145 BACKGROUND Invasive adenocarcinoma 112:145 BACKGROUND Invasive adenocarcinoma (IAC) 112:151 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 3 48 theme cancer 619:624 arg1 patients 626:633 four multiple primary lung cancer patients 592:633 four multiple primary lung cancer patients 592:633 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 11 49 theme novel 1753:1757 arg1 target 1759:1764 a novel target 1751:1764 a novel target for LUAD intervention and immunotherapy 1751:1804 CONCLUSION B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy. 37303063 2 50 from MIA 371:373 arg1 progression 354:364 the progression 350:364 the progression from MIA to IAC 350:380 Identifying the molecular events underlying the progression from MIA to IAC may provide a crucial perspective and boost the exploration of novel strategies for early-stage LUAD diagnosis and treatment. 37303063 9 51 theme cancer 1489:1494 arg1 escape 1503:1508 lung cancer immune escape 1484:1508 lung cancer immune escape 1484:1508 These factors lead to lung cancer immune escape. 37303063 8 52 theme TAZ 1379:1381 arg1 protein 1383:1389 the TAZ protein 1375:1389 the TAZ protein 1375:1389 In addition, B4GALT1 stabilized the TAZ protein via glycosylation, which activated CD274 at the transcriptional level. 37303063 10 53 theme antitumour 1609:1618 arg1 immunity 1620:1627 the antitumour immunity 1605:1627 the antitumour immunity of anti-PD-1 therapy 1605:1648 Importantly, inhibition of B4GALT1 increased CD8 + T-cell abundance and activity and enhanced the antitumour immunity of anti-PD-1 therapy in vivo. 37303063 3 54 theme IAC 566:568 arg1 tumours 570:576 IAC tumours 566:576 IAC tumours obtained from four multiple primary lung cancer patients 566:633 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 5 55 dep RESULTS 902:908 arg1 gene 925:928 a key gene 919:928 a key gene involved in N-glycan biosynthesis 919:962 RESULTS B4GALT1, a key gene involved in N-glycan biosynthesis, was highly expressed in IAC samples. 37303063 5 55 dep RESULTS 902:908 arg1 B4GALT1 910:916 B4GALT1 910:916 B4GALT1 910:916 RESULTS B4GALT1, a key gene involved in N-glycan biosynthesis, was highly expressed in IAC samples. 37303063 2 56 theme molecular 322:330 arg1 events 332:337 the molecular events 318:337 the molecular events underlying the progression from MIA to IAC 318:380 Identifying the molecular events underlying the progression from MIA to IAC may provide a crucial perspective and boost the exploration of novel strategies for early-stage LUAD diagnosis and treatment. 37303063 4 57 dep death 878:882 arg1 ligand 884:889 ligand 1 884:891 programmed cell death ligand 1 (PD-L1) 862:899 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 4 57 dep death 878:882 arg1 PD-L1 894:898 PD-L1 894:898 PD-L1 894:898 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 11 58 from target 1759:1764 arg1 development 1708:1718 the development 1704:1718 the development of early-stage LUAD 1704:1738 CONCLUSION B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy. 37303063 10 59 theme CD8 + T-cell 1556:1567 arg1 abundance 1569:1577 CD8 + T-cell abundance 1556:1577 CD8 + T-cell abundance 1556:1577 Importantly, inhibition of B4GALT1 increased CD8 + T-cell abundance and activity and enhanced the antitumour immunity of anti-PD-1 therapy in vivo. 37303063 3 60 theme tumours 570:576 arg1 sequencing 530:539 METHODS Transcriptome sequencing 508:539 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients 508:633 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 1 61 theme BACKGROUND 112:121 arg1 IAC 148:150 IAC 148:150 IAC 148:150 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 1 61 theme BACKGROUND 112:121 arg1 subtype 255:261 the dominant pathological subtype 229:261 the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD) 229:303 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 1 61 theme BACKGROUND 112:121 arg1 adenocarcinoma 132:145 BACKGROUND Invasive adenocarcinoma 112:145 BACKGROUND Invasive adenocarcinoma (IAC) 112:151 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 4 62 theme regulatory 792:801 arg1 mechanism 803:811 the regulatory mechanism 788:811 the regulatory mechanism of B4GALT1-mediated immune evasion 788:846 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 3 63 theme primary 606:612 arg1 patients 626:633 four multiple primary lung cancer patients 592:633 four multiple primary lung cancer patients 592:633 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 1 64 theme Invasive 123:130 arg1 IAC 148:150 IAC 148:150 IAC 148:150 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 1 64 theme Invasive 123:130 arg1 subtype 255:261 the dominant pathological subtype 229:261 the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD) 229:303 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 1 64 theme Invasive 123:130 arg1 adenocarcinoma 132:145 BACKGROUND Invasive adenocarcinoma 112:145 BACKGROUND Invasive adenocarcinoma (IAC) 112:151 BACKGROUND Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). 37303063 4 65 theme in 754:755 arg1 experiments 729:739 Function and mechanism experiments 706:739 Function and mechanism experiments in vitro and in vivo 706:760 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 3 66 theme lung 614:617 arg1 patients 626:633 four multiple primary lung cancer patients 592:633 four multiple primary lung cancer patients 592:633 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 4 67 theme mechanism 719:727 arg1 experiments 729:739 Function and mechanism experiments 706:739 Function and mechanism experiments in vitro and in vivo 706:760 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 37303063 5 68 theme key 921:923 arg1 gene 925:928 a key gene 919:928 a key gene involved in N-glycan biosynthesis 919:962 RESULTS B4GALT1, a key gene involved in N-glycan biosynthesis, was highly expressed in IAC samples. 37303063 5 68 theme key 921:923 arg1 B4GALT1 910:916 B4GALT1 910:916 B4GALT1 910:916 RESULTS B4GALT1, a key gene involved in N-glycan biosynthesis, was highly expressed in IAC samples. 37303063 0 69 theme PD-L1 63:67 arg1 expression 49:58 the expression 45:58 the expression of PD-L1 at multiple levels in lung adenocarcinoma 45:109 B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma. 37303063 0 70 from levels 81:86 arg1 adenocarcinoma 96:109 lung adenocarcinoma 91:109 lung adenocarcinoma 91:109 B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma. 37303063 0 70 from levels 81:86 arg1 expression 49:58 the expression 45:58 the expression of PD-L1 at multiple levels in lung adenocarcinoma 45:109 B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma. 37303063 5 71 theme IAC 989:991 arg1 samples 993:999 IAC samples 989:999 IAC samples 989:999 RESULTS B4GALT1, a key gene involved in N-glycan biosynthesis, was highly expressed in IAC samples. 37303063 6 72 theme LUAD 1054:1057 arg1 cell 1059:1062 LUAD cell proliferation and invasion 1054:1089 cell 1059:1062 Further experiments revealed that B4GALT1 regulated LUAD cell proliferation and invasion both in vitro and in vivo and was related to the impaired antitumour capacity of CD8 + T cells. 37303063 6 73 theme Further 1002:1008 arg1 experiments 1010:1020 Further experiments 1002:1020 Further experiments 1002:1020 Further experiments revealed that B4GALT1 regulated LUAD cell proliferation and invasion both in vitro and in vivo and was related to the impaired antitumour capacity of CD8 + T cells. 37303063 2 74 theme LUAD 478:481 arg1 diagnosis 483:491 early-stage LUAD diagnosis 466:491 early-stage LUAD diagnosis 466:491 Identifying the molecular events underlying the progression from MIA to IAC may provide a crucial perspective and boost the exploration of novel strategies for early-stage LUAD diagnosis and treatment. 37303063 3 75 theme multiple 597:604 arg1 patients 626:633 four multiple primary lung cancer patients 592:633 four multiple primary lung cancer patients 592:633 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 7 76 theme protein 1266:1272 arg1 glycosylation 1243:1255 the N-linked glycosylation 1230:1255 the N-linked glycosylation of PD-L1 protein 1230:1272 Mechanistically, B4GALT1 directly mediates the N-linked glycosylation of PD-L1 protein, thus preventing PD-L1 degradation at the posttranscriptional level. 37303063 3 77 theme METHODS 508:514 arg1 sequencing 530:539 METHODS Transcriptome sequencing 508:539 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients 508:633 METHODS Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). 37303063 4 78 theme Function 706:713 arg1 experiments 729:739 Function and mechanism experiments 706:739 Function and mechanism experiments in vitro and in vivo 706:760 Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). 35339830 2 0 theme Orbitrap 103:110 arg1 spectrometry 117:128 UHPLC-Q-Exactive Orbitrap Mass spectrometry 86:128 UHPLC-Q-Exactive Orbitrap Mass spectrometry 86:128 by UHPLC-Q-Exactive Orbitrap Mass spectrometry and assessment of their antioxidant and anti-inflammatory activities. 35339830 8 1 theme DPPH 981:984 arg1 abilities 997:1005 decent potent •OH and DPPH scavenging abilities 959:1005 abilities 997:1005 EKL present decent potent •OH and DPPH scavenging abilities and Fe2+ chelating ability. 35339830 9 2 theme anti-inflammatory 1217:1233 arg1 IL-10 1244:1248 anti-inflammatory cytokine IL-10 1217:1248 anti-inflammatory cytokine IL-10 1217:1248 They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. 35339830 5 3 theme first 683:687 arg1 time 689:692 the first time 679:692 the first time in the plant of kadsua coccinea 679:724 All these chemicals were reported for the first time in leaves, and 95 of them have been reported for the first time in the plant of kadsua coccinea. 35339830 2 4 theme UHPLC-Q-Exactive 86:101 arg1 spectrometry 117:128 UHPLC-Q-Exactive Orbitrap Mass spectrometry 86:128 UHPLC-Q-Exactive Orbitrap Mass spectrometry 86:128 by UHPLC-Q-Exactive Orbitrap Mass spectrometry and assessment of their antioxidant and anti-inflammatory activities. 35339830 6 5 theme extracts 755:762 arg1 potential 742:750 The biological potential 727:750 The biological potential of extracts of K. coccinea leaves (EKL) 727:790 The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. 35339830 4 6 theme chemical 397:404 arg1 lignans 470:476 4 lignans 468:476 4 lignans 468:476 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 35339830 4 6 theme chemical 397:404 arg1 flavonoids 452:461 41 flavonoids 449:461 41 flavonoids 449:461 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 35339830 4 6 theme chemical 397:404 arg1 acids 442:446 53 phenolic acids 430:446 53 phenolic acids 430:446 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 35339830 4 6 theme chemical 397:404 arg1 constituents 406:417 98 chemical constituents 394:417 98 chemical constituents 394:417 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 35339830 8 7 theme scavenging 986:995 arg1 abilities 997:1005 decent potent •OH and DPPH scavenging abilities 959:1005 abilities 997:1005 EKL present decent potent •OH and DPPH scavenging abilities and Fe2+ chelating ability. 35339830 10 8 theme further 1374:1380 arg1 development 1382:1392 further development 1374:1392 further development 1374:1392 These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves. 35339830 4 9 theme coccinea 520:527 arg1 plant 504:508 the plant 500:508 the plant of kadsua coccinea 500:527 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 35339830 5 10 theme them 651:654 arg1 them 651:654 them 651:654 them 651:654 All these chemicals were reported for the first time in leaves, and 95 of them have been reported for the first time in the plant of kadsua coccinea. 35339830 5 10 theme them 651:654 arg1 95 645:646 95 645:646 95 645:646 All these chemicals were reported for the first time in leaves, and 95 of them have been reported for the first time in the plant of kadsua coccinea. 35339830 4 11 theme kadsua 513:518 arg1 coccinea 520:527 kadsua coccinea 513:527 kadsua coccinea 513:527 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 35339830 3 12 theme its 307:309 arg1 composition 292:302 the composition 288:302 the composition of its leaves 288:316 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 3 12 theme its 307:309 arg1 activities 326:335 the activities 322:335 the activities of its constituents 322:355 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 10 13 dep coccinea 1422:1429 arg1 leaves 1431:1436 leaves 1431:1436 leaves 1431:1436 These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves. 35339830 8 14 theme decent 959:964 arg1 •OH 973:975 decent potent •OH and DPPH scavenging abilities 959:1005 •OH 973:975 EKL present decent potent •OH and DPPH scavenging abilities and Fe2+ chelating ability. 35339830 9 15 theme IL-10 1244:1248 arg1 secretion 1204:1212 the secretion 1200:1212 the secretion of anti-inflammatory cytokine IL-10 1200:1248 They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. 35339830 9 16 theme cytokine 1235:1242 arg1 IL-10 1244:1248 anti-inflammatory cytokine IL-10 1217:1248 anti-inflammatory cytokine IL-10 1217:1248 They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. 35339830 10 17 theme antioxidant 1287:1297 arg1 activities 1321:1330 significant antioxidant and anti-inflammatory activities 1275:1330 significant antioxidant and anti-inflammatory activities 1275:1330 These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves. 35339830 3 18 theme Kadsua 200:205 arg1 coccinea 220:227 coccinea 220:227 coccinea 220:227 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 3 18 theme Kadsua 200:205 arg1 medicine 269:276 a fruit and folk medicine 252:276 a fruit and folk medicine 252:276 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 3 18 theme Kadsua 200:205 arg1 coccinea 207:214 Kadsua coccinea 200:214 Kadsua coccinea (K. coccinea) 200:228 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 0 19 theme Chemical 0:7 arg1 Lem 68:70 Lem 68:70 Lem 68:70 Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) 35339830 0 19 theme Chemical 0:7 arg1 characterization 9:24 Chemical characterization 0:24 Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) 0:72 Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) 35339830 3 20 used used 244:247 arg2 coccinea 207:214 Kadsua coccinea 200:214 Kadsua coccinea (K. coccinea) 200:228 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 3 20 used used 244:247 arg2 medicine 269:276 a fruit and folk medicine 252:276 a fruit and folk medicine 252:276 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 3 20 used used 244:247 arg2 coccinea 220:227 coccinea 220:227 coccinea 220:227 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 8 21 theme chelating 1016:1024 arg1 ability 1026:1032 Fe2+ chelating ability 1011:1032 Fe2+ chelating ability 1011:1032 EKL present decent potent •OH and DPPH scavenging abilities and Fe2+ chelating ability. 35339830 4 22 theme phenolic 433:440 arg1 acids 442:446 53 phenolic acids 430:446 53 phenolic acids 430:446 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 35339830 10 23 theme significant 1275:1285 arg1 activities 1321:1330 significant antioxidant and anti-inflammatory activities 1275:1330 significant antioxidant and anti-inflammatory activities 1275:1330 These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves. 35339830 5 24 from time 689:692 arg1 plant 701:705 the plant 697:705 the plant of kadsua coccinea 697:724 All these chemicals were reported for the first time in leaves, and 95 of them have been reported for the first time in the plant of kadsua coccinea. 35339830 10 25 theme coccinea 1422:1429 arg1 investigation 1398:1410 investigation 1398:1410 investigation 1398:1410 These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves. 35339830 10 25 theme coccinea 1422:1429 arg1 development 1382:1392 further development 1374:1392 further development 1374:1392 These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves. 35339830 3 26 theme constituents 344:355 arg1 composition 292:302 the composition 288:302 the composition of its leaves 288:316 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 3 26 theme constituents 344:355 arg1 activities 326:335 the activities 322:335 the activities of its constituents 322:355 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 9 27 theme pro-inflammatory 1137:1152 arg1 IL-2 1173:1176 IL-2 1173:1176 IL-2 1173:1176 They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. 35339830 9 27 theme pro-inflammatory 1137:1152 arg1 cytokines 1154:1162 pro-inflammatory cytokines 1137:1162 pro-inflammatory cytokines 1137:1162 They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. 35339830 9 27 theme pro-inflammatory 1137:1152 arg1 IL-6 1182:1185 IL-6 1182:1185 IL-6 1182:1185 They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. 35339830 10 28 theme EKL 1335:1337 arg1 activities 1321:1330 significant antioxidant and anti-inflammatory activities 1275:1330 significant antioxidant and anti-inflammatory activities 1275:1330 These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves. 35339830 0 29 theme extracts 29:36 arg1 Lem 68:70 Lem 68:70 Lem 68:70 Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) 35339830 0 29 theme extracts 29:36 arg1 characterization 9:24 Chemical characterization 0:24 Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) 0:72 Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) 35339830 5 30 theme kadsua 710:715 arg1 coccinea 717:724 kadsua coccinea 710:724 kadsua coccinea 710:724 All these chemicals were reported for the first time in leaves, and 95 of them have been reported for the first time in the plant of kadsua coccinea. 35339830 3 31 theme fruit 254:258 arg1 medicine 269:276 a fruit and folk medicine 252:276 a fruit and folk medicine 252:276 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 3 31 theme fruit 254:258 arg1 coccinea 207:214 Kadsua coccinea 200:214 Kadsua coccinea (K. coccinea) 200:228 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 8 32 theme potent 966:971 arg1 •OH 973:975 decent potent •OH and DPPH scavenging abilities 959:1005 •OH 973:975 EKL present decent potent •OH and DPPH scavenging abilities and Fe2+ chelating ability. 35339830 2 33 theme anti-inflammatory 170:186 arg1 activities 188:197 their antioxidant and anti-inflammatory activities 148:197 their antioxidant and anti-inflammatory activities 148:197 by UHPLC-Q-Exactive Orbitrap Mass spectrometry and assessment of their antioxidant and anti-inflammatory activities. 35339830 9 34 theme Cox2 1094:1097 arg1 level 1085:1089 the level 1081:1089 the level of Cox2 in proteins 1081:1109 They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. 35339830 0 35 theme leaves 41:46 arg1 extracts 29:36 extracts 29:36 extracts of leaves of Kadsua coccinea 29:65 Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) 35339830 6 36 theme anti-inflammatory 840:856 arg1 assay 858:862 anti-inflammatory assay 840:862 anti-inflammatory assay 840:862 The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. 35339830 9 37 theme cytokines 1154:1162 arg1 secretion 1124:1132 the secretion 1120:1132 the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6 1120:1185 They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. 35339830 10 38 theme anti-inflammatory 1303:1319 arg1 activities 1321:1330 significant antioxidant and anti-inflammatory activities 1275:1330 significant antioxidant and anti-inflammatory activities 1275:1330 These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves. 35339830 2 39 theme antioxidant 154:164 arg1 activities 188:197 their antioxidant and anti-inflammatory activities 148:197 their antioxidant and anti-inflammatory activities 148:197 by UHPLC-Q-Exactive Orbitrap Mass spectrometry and assessment of their antioxidant and anti-inflammatory activities. 35339830 5 40 theme coccinea 717:724 arg1 plant 701:705 the plant 697:705 the plant of kadsua coccinea 697:724 All these chemicals were reported for the first time in leaves, and 95 of them have been reported for the first time in the plant of kadsua coccinea. 35339830 0 41 theme Kadsua 51:56 arg1 coccinea 58:65 Kadsua coccinea 51:65 Kadsua coccinea 51:65 Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) 35339830 3 42 dep its 307:309 arg1 leaves 311:316 leaves 311:316 leaves 311:316 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 4 43 theme constituents 406:417 arg1 total 385:389 A total 383:389 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, 383:477 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 35339830 6 44 theme coccinea 770:777 arg1 extracts 755:762 extracts 755:762 extracts of K. coccinea leaves (EKL) 755:790 The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. 35339830 6 45 theme antioxidant 818:828 arg1 assay 830:834 in vitro antioxidant assay 809:834 in vitro antioxidant assay 809:834 The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. 35339830 5 46 theme first 619:623 arg1 time 625:628 the first time 615:628 the first time 615:628 All these chemicals were reported for the first time in leaves, and 95 of them have been reported for the first time in the plant of kadsua coccinea. 35339830 9 47 theme NO 1070:1071 arg1 secretion 1057:1065 the secretion 1053:1065 the secretion of NO 1053:1071 They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. 35339830 3 48 theme folk 264:267 arg1 medicine 269:276 a fruit and folk medicine 252:276 a fruit and folk medicine 252:276 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 3 48 theme folk 264:267 arg1 coccinea 207:214 Kadsua coccinea 200:214 Kadsua coccinea (K. coccinea) 200:228 Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. 35339830 4 49 theme UHPLC-Q-Exactive 532:547 arg1 spectrometry 563:574 UHPLC-Q-Exactive Orbitrap Mass spectrometry 532:574 UHPLC-Q-Exactive Orbitrap Mass spectrometry 532:574 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 35339830 6 50 theme biological 731:740 arg1 potential 742:750 The biological potential 727:750 The biological potential of extracts of K. coccinea leaves (EKL) 727:790 The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. 35339830 8 51 theme Fe2+ 1011:1014 arg1 ability 1026:1032 Fe2+ chelating ability 1011:1032 Fe2+ chelating ability 1011:1032 EKL present decent potent •OH and DPPH scavenging abilities and Fe2+ chelating ability. 35339830 9 52 from level 1085:1089 arg1 proteins 1102:1109 proteins 1102:1109 proteins 1102:1109 They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. 35339830 6 53 theme in 809:810 arg1 assay 830:834 in vitro antioxidant assay 809:834 in vitro antioxidant assay 809:834 The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. 35339830 2 54 theme activities 188:197 arg1 assessment 134:143 assessment 134:143 assessment 134:143 by UHPLC-Q-Exactive Orbitrap Mass spectrometry and assessment of their antioxidant and anti-inflammatory activities. 35339830 2 54 theme activities 188:197 arg1 spectrometry 117:128 UHPLC-Q-Exactive Orbitrap Mass spectrometry 86:128 UHPLC-Q-Exactive Orbitrap Mass spectrometry 86:128 by UHPLC-Q-Exactive Orbitrap Mass spectrometry and assessment of their antioxidant and anti-inflammatory activities. 35339830 1 55 dep Sm 79:80 arg1 A.C. 74:77 A.C. 74:77 A.C. 74:77 A.C. Sm. 35339830 4 56 theme Mass 558:561 arg1 spectrometry 563:574 UHPLC-Q-Exactive Orbitrap Mass spectrometry 532:574 UHPLC-Q-Exactive Orbitrap Mass spectrometry 532:574 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 35339830 6 57 dep in 809:810 arg1 vitro 812:816 vitro 812:816 vitro 812:816 The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. 35339830 2 58 theme Mass 112:115 arg1 spectrometry 117:128 UHPLC-Q-Exactive Orbitrap Mass spectrometry 86:128 UHPLC-Q-Exactive Orbitrap Mass spectrometry 86:128 by UHPLC-Q-Exactive Orbitrap Mass spectrometry and assessment of their antioxidant and anti-inflammatory activities. 35339830 10 59 theme kadsua 1415:1420 arg1 coccinea 1422:1429 kadsua coccinea 1415:1429 kadsua coccinea leaves 1415:1436 These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves. 35339830 6 60 dep coccinea 770:777 arg1 EKL 787:789 EKL 787:789 EKL 787:789 The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. 35339830 6 60 dep coccinea 770:777 arg1 leaves 779:784 leaves 779:784 leaves 779:784 The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. 35339830 4 61 theme Orbitrap 549:556 arg1 spectrometry 563:574 UHPLC-Q-Exactive Orbitrap Mass spectrometry 532:574 UHPLC-Q-Exactive Orbitrap Mass spectrometry 532:574 A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. 36365515 2 0 theme maximum 323:329 arg1 yield 346:350 The maximum polysaccharide yield 319:350 The maximum polysaccharide yield of up to 9.68 wt% 319:368 The maximum polysaccharide yield of up to 9.68 wt% was reported. 36365515 6 1 theme hemicelluloses 1189:1202 arg1 structure 1163:1171 the structure 1159:1171 the structure of the obtained hemicelluloses 1159:1202 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 6 2 from cm-1 1096:1099 arg1 signal 1061:1066 a weak lignin absorption signal 1036:1066 a weak lignin absorption signal in the spectra at 1500-1510 cm-1 1036:1099 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 6 2 from cm-1 1096:1099 arg1 spectra 1075:1081 the spectra 1071:1081 the spectra at 1500-1510 cm-1 1071:1099 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 3 3 theme permeation 505:514 arg1 chromatography 516:529 gas and gel permeation chromatography 493:529 chromatography 516:529 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 9 4 theme polysaccharides 1665:1679 arg1 activity 1649:1656 the activity 1645:1656 the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals 1645:1722 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 9 4 theme polysaccharides 1665:1679 arg1 lower 1727:1731 lower 1727:1731 lower 1727:1731 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 4 5 theme xylose 653:658 arg1 units 701:705 The xylose, mannose, galactose, and glucose monomer units 649:705 The xylose, mannose, galactose, and glucose monomer units 649:705 The xylose, mannose, galactose, and glucose monomer units were identified in the hemicelluloses by gas chromatography. 36365515 6 6 from signal 1061:1066 arg1 spectra 1075:1081 the spectra 1071:1081 the spectra at 1500-1510 cm-1 1071:1099 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 6 6 from signal 1061:1066 arg1 cm-1 1096:1099 1500-1510 cm-1 1086:1099 1500-1510 cm-1 1086:1099 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 9 7 theme neutralizing 1684:1695 arg1 DPPH 1697:1700 neutralizing DPPH 1684:1700 neutralizing DPPH 1684:1700 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 4 8 theme mannose 661:667 arg1 units 701:705 The xylose, mannose, galactose, and glucose monomer units 649:705 The xylose, mannose, galactose, and glucose monomer units 649:705 The xylose, mannose, galactose, and glucose monomer units were identified in the hemicelluloses by gas chromatography. 36365515 3 9 theme infrared 550:557 arg1 spectroscopy 559:570 Fourier-transform infrared spectroscopy 532:570 Fourier-transform infrared spectroscopy 532:570 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 1 10 from temperatures 264:275 arg1 medium 254:259 an acetic acid-water-hydrogen peroxide medium 215:259 an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h 215:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 1 10 from temperatures 264:275 arg1 delignification 196:210 oxidative delignification 186:210 oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h 186:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 3 11 theme physicochemical 468:482 arg1 methods 484:490 physicochemical methods 468:490 physicochemical methods 468:490 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 6 12 theme hemicelluloses 958:971 arg1 spectra 943:949 The reported Fourier-transform spectra 912:949 The reported Fourier-transform spectra of the hemicelluloses 912:971 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 5 13 located found 871:875 arg2 Mw 804:805 The weight average molecular weight Mw 768:805 The weight average molecular weight Mw of the products determined by gel permeation chromatography 768:865 The weight average molecular weight Mw of the products determined by gel permeation chromatography was found to range within 8932-33,142 g/mol. 36365515 5 13 located found 871:875 arg1 g/mol 905:909 8932-33,142 g/mol 893:909 8932-33,142 g/mol 893:909 The weight average molecular weight Mw of the products determined by gel permeation chromatography was found to range within 8932-33,142 g/mol. 36365515 3 14 theme nuclear 576:582 arg1 resonance 593:601 2D nuclear magnetic resonance 573:601 2D nuclear magnetic resonance spectroscopy 573:614 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 5 15 theme gel 837:839 arg1 chromatography 852:865 gel permeation chromatography 837:865 gel permeation chromatography 837:865 The weight average molecular weight Mw of the products determined by gel permeation chromatography was found to range within 8932-33,142 g/mol. 36365515 7 16 theme further 1379:1385 arg1 heating 1387:1393 further heating 1379:1393 further heating up to 400 °C 1379:1406 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 4 17 theme monomer 693:699 arg1 units 701:705 The xylose, mannose, galactose, and glucose monomer units 649:705 The xylose, mannose, galactose, and glucose monomer units 649:705 The xylose, mannose, galactose, and glucose monomer units were identified in the hemicelluloses by gas chromatography. 36365515 6 18 theme Fourier-transform 925:941 arg1 spectra 943:949 The reported Fourier-transform spectra 912:949 The reported Fourier-transform spectra of the hemicelluloses 912:971 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 6 19 theme weak 1038:1041 arg1 signal 1061:1066 a weak lignin absorption signal 1036:1066 a weak lignin absorption signal in the spectra at 1500-1510 cm-1 1036:1099 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 7 20 theme °C 1366:1367 arg1 temperatures 1337:1348 temperatures 1337:1348 temperatures of up to 90-100 °C 1337:1367 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 4 21 theme galactose 670:678 arg1 units 701:705 The xylose, mannose, galactose, and glucose monomer units 649:705 The xylose, mannose, galactose, and glucose monomer units 649:705 The xylose, mannose, galactose, and glucose monomer units were identified in the hemicelluloses by gas chromatography. 36365515 3 22 theme resonance 593:601 arg1 spectroscopy 603:614 2D nuclear magnetic resonance spectroscopy 573:614 2D nuclear magnetic resonance spectroscopy 573:614 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 7 23 dep °C 1405:1406 arg1 up 1395:1396 up 1395:1396 up 1395:1396 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 9 24 theme vitamin 1765:1771 arg1 C 1773:1773 vitamin C 1765:1773 vitamin C 1765:1773 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 7 25 theme analysis 1234:1241 arg1 use 1209:1211 The use 1205:1211 The use of thermogravimetric analysis 1205:1241 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 4 26 theme gas 748:750 arg1 chromatography 752:765 gas chromatography 748:765 gas chromatography 748:765 The xylose, mannose, galactose, and glucose monomer units were identified in the hemicelluloses by gas chromatography. 36365515 0 27 theme Oxidative 80:88 arg1 Delignification 90:104 Oxidative Delignification 80:104 Oxidative Delignification 80:104 Composition and Structure of Aspen (Pópulus trémula) Hemicelluloses Obtained by Oxidative Delignification. 36365515 6 28 theme obtained 1180:1187 arg1 hemicelluloses 1189:1202 the obtained hemicelluloses 1176:1202 the obtained hemicelluloses 1176:1202 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 2 29 theme wt 366:367 arg1 % 368:368 up to 9.68 wt% 355:368 up to 9.68 wt% 355:368 The maximum polysaccharide yield of up to 9.68 wt% was reported. 36365515 1 30 dep wood 146:149 arg1 trémula 160:166 Pópulus trémula 152:166 Pópulus trémula 152:166 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 3 31 theme hemicelluloses 421:434 arg1 structure 404:412 structure 404:412 structure 404:412 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 3 31 theme hemicelluloses 421:434 arg1 composition 388:398 composition 388:398 composition 388:398 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 1 32 theme °C 287:288 arg1 time 304:307 a process time 294:307 a process time of 1-4 h 294:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 1 32 theme °C 287:288 arg1 temperatures 264:275 temperatures 264:275 temperatures of 70-100 °C 264:288 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 0 33 theme Aspen 29:33 arg1 Structure 16:24 Structure 16:24 Structure 16:24 Composition and Structure of Aspen (Pópulus trémula) Hemicelluloses Obtained by Oxidative Delignification. 36365515 0 33 theme Aspen 29:33 arg1 Composition 0:10 Composition 0:10 Composition 0:10 Composition and Structure of Aspen (Pópulus trémula) Hemicelluloses Obtained by Oxidative Delignification. 36365515 5 34 theme weight 772:777 arg1 Mw 804:805 The weight average molecular weight Mw 768:805 The weight average molecular weight Mw of the products determined by gel permeation chromatography 768:865 The weight average molecular weight Mw of the products determined by gel permeation chromatography was found to range within 8932-33,142 g/mol. 36365515 3 35 dep composition 388:398 arg1 The 384:386 The 384:386 The 384:386 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 6 36 theme absorption 1050:1059 arg1 signal 1061:1066 a weak lignin absorption signal 1036:1066 a weak lignin absorption signal in the spectra at 1500-1510 cm-1 1036:1099 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 3 37 theme thermogravimetric 621:637 arg1 analysis 639:646 thermogravimetric analysis 621:646 thermogravimetric analysis 621:646 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 5 38 theme molecular 787:795 arg1 Mw 804:805 The weight average molecular weight Mw 768:805 The weight average molecular weight Mw of the products determined by gel permeation chromatography 768:865 The weight average molecular weight Mw of the products determined by gel permeation chromatography was found to range within 8932-33,142 g/mol. 36365515 7 39 dep 90-100 1359:1364 arg1 to 1356:1357 to 1356:1357 to 1356:1357 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 6 40 theme minor 1120:1124 arg1 content 1126:1132 a minor content 1118:1132 a minor content of phenolic fragments in the structure of the obtained hemicelluloses 1118:1202 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 8 41 theme salicylic 1610:1618 arg1 radicals 1600:1607 hydroxyl radicals 1591:1607 hydroxyl radicals (salicylic acid) 1591:1624 The antioxidant activity of the hemicelluloses was examined using the compounds that mimic free radicals (1,1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals (salicylic acid). 36365515 8 41 theme salicylic 1610:1618 arg1 acid 1620:1623 salicylic acid 1610:1623 salicylic acid 1610:1623 The antioxidant activity of the hemicelluloses was examined using the compounds that mimic free radicals (1,1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals (salicylic acid). 36365515 3 42 theme methods 484:490 arg1 complex 457:463 a complex 455:463 a complex of physicochemical methods 455:490 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 1 43 theme acetic 218:223 arg1 medium 254:259 an acetic acid-water-hydrogen peroxide medium 215:259 an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h 215:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 6 44 theme reported 916:923 arg1 spectra 943:949 The reported Fourier-transform spectra 912:949 The reported Fourier-transform spectra of the hemicelluloses 912:971 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 9 45 theme 81.7 1842:1845 arg1 % 1855:1855 81.7 and 82.9% 1842:1855 % 1855:1855 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 7 46 attach isolated 1279:1286 arg2 resistant 1308:1316 resistant 1308:1316 resistant 1308:1316 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 7 46 attach isolated 1279:1286 arg1 wood 1299:1302 aspen wood 1293:1302 aspen wood 1293:1302 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 7 46 attach isolated 1279:1286 arg2 hemicelluloses 1264:1277 the hemicelluloses 1260:1277 the hemicelluloses isolated from aspen wood 1260:1302 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 1 47 from time 304:307 arg1 medium 254:259 an acetic acid-water-hydrogen peroxide medium 215:259 an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h 215:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 1 47 from time 304:307 arg1 delignification 196:210 oxidative delignification 186:210 oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h 186:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 2 48 theme polysaccharide 331:344 arg1 yield 346:350 The maximum polysaccharide yield 319:350 The maximum polysaccharide yield of up to 9.68 wt% 319:368 The maximum polysaccharide yield of up to 9.68 wt% was reported. 36365515 1 49 theme peroxide 245:252 arg1 medium 254:259 an acetic acid-water-hydrogen peroxide medium 215:259 an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h 215:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 9 50 theme 82.9 1851:1854 arg1 % 1855:1855 81.7 and 82.9% 1842:1855 % 1855:1855 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 3 51 theme gel 501:503 arg1 chromatography 516:529 gas and gel permeation chromatography 493:529 chromatography 516:529 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 7 52 theme increasing 1433:1442 arg1 rate 1444:1447 an increasing rate 1430:1447 an increasing rate 1430:1447 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 3 53 theme gas 493:495 arg1 chromatography 516:529 gas and gel permeation chromatography 493:529 chromatography 516:529 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 5 54 theme permeation 841:850 arg1 chromatography 852:865 gel permeation chromatography 837:865 gel permeation chromatography 837:865 The weight average molecular weight Mw of the products determined by gel permeation chromatography was found to range within 8932-33,142 g/mol. 36365515 3 55 theme Fourier-transform 532:548 arg1 spectroscopy 559:570 Fourier-transform infrared spectroscopy 532:570 Fourier-transform infrared spectroscopy 532:570 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 7 56 theme start 1409:1413 arg1 destructing 1415:1425 start destructing 1409:1425 start destructing 1409:1425 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 5 57 theme products 814:821 arg1 Mw 804:805 The weight average molecular weight Mw 768:805 The weight average molecular weight Mw of the products determined by gel permeation chromatography 768:865 The weight average molecular weight Mw of the products determined by gel permeation chromatography was found to range within 8932-33,142 g/mol. 36365515 9 58 theme hydroxyl 1706:1713 arg1 radicals 1715:1722 hydroxyl radicals 1706:1722 hydroxyl radicals 1706:1722 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 6 59 theme fragments 1146:1154 arg1 content 1126:1132 a minor content 1118:1132 a minor content of phenolic fragments in the structure of the obtained hemicelluloses 1118:1202 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 3 60 theme 2D 573:574 arg1 resonance 593:601 2D nuclear magnetic resonance 573:601 2D nuclear magnetic resonance spectroscopy 573:614 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 1 61 theme oxidative 186:194 arg1 delignification 196:210 oxidative delignification 186:210 oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h 186:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 8 62 theme antioxidant 1454:1464 arg1 activity 1466:1473 The antioxidant activity 1450:1473 The antioxidant activity of the hemicelluloses 1450:1495 The antioxidant activity of the hemicelluloses was examined using the compounds that mimic free radicals (1,1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals (salicylic acid). 36365515 1 63 from delignification 196:210 arg1 medium 254:259 an acetic acid-water-hydrogen peroxide medium 215:259 an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h 215:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 1 63 from delignification 196:210 arg1 time 304:307 a process time 294:307 a process time of 1-4 h 294:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 1 63 from delignification 196:210 arg1 temperatures 264:275 temperatures 264:275 temperatures of 70-100 °C 264:288 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 4 64 theme glucose 685:691 arg1 monomer 693:699 glucose monomer 685:699 glucose monomer 685:699 The xylose, mannose, galactose, and glucose monomer units were identified in the hemicelluloses by gas chromatography. 36365515 6 65 theme lignin 1043:1048 arg1 signal 1061:1066 a weak lignin absorption signal 1036:1066 a weak lignin absorption signal in the spectra at 1500-1510 cm-1 1036:1099 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 9 66 theme absorption 1742:1751 arg1 capacity 1753:1760 the absorption capacity 1738:1760 the absorption capacity of vitamin C 1738:1773 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 8 67 theme hemicelluloses 1482:1495 arg1 activity 1466:1473 The antioxidant activity 1450:1473 The antioxidant activity of the hemicelluloses 1450:1495 The antioxidant activity of the hemicelluloses was examined using the compounds that mimic free radicals (1,1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals (salicylic acid). 36365515 3 68 theme magnetic 584:591 arg1 resonance 593:601 2D nuclear magnetic resonance 573:601 2D nuclear magnetic resonance spectroscopy 573:614 The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. 36365515 7 69 theme thermogravimetric 1216:1232 arg1 analysis 1234:1241 thermogravimetric analysis 1216:1241 thermogravimetric analysis 1216:1241 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 1 70 theme h 316:316 arg1 time 304:307 a process time 294:307 a process time of 1-4 h 294:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 1 70 theme h 316:316 arg1 temperatures 264:275 temperatures 264:275 temperatures of 70-100 °C 264:288 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 1 71 theme wood 146:149 arg1 hemicelluloses 122:135 hemicelluloses 122:135 hemicelluloses of aspen wood (Pópulus trémula) 122:167 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 6 72 theme heteropolysaccharides 1013:1033 arg1 characteristic 995:1008 characteristic 995:1008 characteristic 995:1008 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 9 73 theme C 1773:1773 arg1 capacity 1753:1760 the absorption capacity 1738:1760 the absorption capacity of vitamin C 1738:1773 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 6 74 theme characteristic 995:1008 arg1 bands 989:993 the bands 985:993 the bands characteristic of heteropolysaccharides 985:1033 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 9 75 theme tested 1786:1791 arg1 concentrations 1793:1806 all the tested concentrations 1778:1806 all the tested concentrations (0.5, 2, and 5 mg/mL) 1778:1828 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 9 75 theme tested 1786:1791 arg1 mg/mL 1823:1827 0.5, 2, and 5 mg/mL 1809:1827 0.5, 2, and 5 mg/mL 1809:1827 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 8 76 theme free 1541:1544 arg1 1,1-diphenyl-2-picrylhydrazyl 1556:1584 1,1-diphenyl-2-picrylhydrazyl 1556:1584 1,1-diphenyl-2-picrylhydrazyl 1556:1584 The antioxidant activity of the hemicelluloses was examined using the compounds that mimic free radicals (1,1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals (salicylic acid). 36365515 8 76 theme free 1541:1544 arg1 radicals 1546:1553 free radicals 1541:1553 free radicals (1,1-diphenyl-2-picrylhydrazyl) 1541:1585 The antioxidant activity of the hemicelluloses was examined using the compounds that mimic free radicals (1,1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals (salicylic acid). 36365515 5 77 theme weight 797:802 arg1 Mw 804:805 The weight average molecular weight Mw 768:805 The weight average molecular weight Mw of the products determined by gel permeation chromatography 768:865 The weight average molecular weight Mw of the products determined by gel permeation chromatography was found to range within 8932-33,142 g/mol. 36365515 0 78 dep Hemicelluloses 53:66 arg1 Obtained 68:75 Obtained 68:75 Hemicelluloses Obtained by Oxidative Delignification 53:104 Composition and Structure of Aspen (Pópulus trémula) Hemicelluloses Obtained by Oxidative Delignification. 36365515 9 79 from activity 1649:1656 arg1 radicals 1715:1722 hydroxyl radicals 1706:1722 hydroxyl radicals 1706:1722 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 9 79 from activity 1649:1656 arg1 DPPH 1697:1700 neutralizing DPPH 1684:1700 neutralizing DPPH 1684:1700 It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively. 36365515 8 80 theme hydroxyl 1591:1598 arg1 radicals 1600:1607 hydroxyl radicals 1591:1607 hydroxyl radicals (salicylic acid) 1591:1624 The antioxidant activity of the hemicelluloses was examined using the compounds that mimic free radicals (1,1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals (salicylic acid). 36365515 8 80 theme hydroxyl 1591:1598 arg1 acid 1620:1623 salicylic acid 1610:1623 salicylic acid 1610:1623 The antioxidant activity of the hemicelluloses was examined using the compounds that mimic free radicals (1,1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals (salicylic acid). 36365515 6 81 contain contain 973:979 arg2 bands 989:993 the bands 985:993 the bands characteristic of heteropolysaccharides 985:1033 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 6 81 contain contain 973:979 arg1 spectra 943:949 The reported Fourier-transform spectra 912:949 The reported Fourier-transform spectra of the hemicelluloses 912:971 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 6 82 from content 1126:1132 arg1 structure 1163:1171 the structure 1159:1171 the structure of the obtained hemicelluloses 1159:1202 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 2 83 theme % 368:368 arg1 yield 346:350 The maximum polysaccharide yield 319:350 The maximum polysaccharide yield of up to 9.68 wt% 319:368 The maximum polysaccharide yield of up to 9.68 wt% was reported. 36365515 5 84 theme average 779:785 arg1 Mw 804:805 The weight average molecular weight Mw 768:805 The weight average molecular weight Mw of the products determined by gel permeation chromatography 768:865 The weight average molecular weight Mw of the products determined by gel permeation chromatography was found to range within 8932-33,142 g/mol. 36365515 1 85 theme process 296:302 arg1 time 304:307 a process time 294:307 a process time of 1-4 h 294:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 6 86 theme phenolic 1137:1144 arg1 fragments 1146:1154 phenolic fragments 1137:1154 phenolic fragments 1137:1154 The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. 36365515 1 87 theme aspen 140:144 arg1 wood 146:149 aspen wood 140:149 aspen wood (Pópulus trémula) 140:167 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36365515 7 88 theme aspen 1293:1297 arg1 wood 1299:1302 aspen wood 1293:1302 aspen wood 1293:1302 The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. 36365515 2 89 dep 9.68 361:364 arg1 to 358:359 to 358:359 to 358:359 The maximum polysaccharide yield of up to 9.68 wt% was reported. 36365515 1 90 theme acid-water-hydrogen 225:243 arg1 medium 254:259 an acetic acid-water-hydrogen peroxide medium 215:259 an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h 215:316 In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. 36004332 8 0 theme vaccine 1428:1434 arg1 strain 1394:1399 the G9 strain 1387:1399 the G9 strain of the Rotavac or Rotasill vaccine 1387:1434 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 7 1 contain possess 1194:1200 arg1 strains 1165:1171 all circulating G3 RVA strains 1142:1171 all circulating G3 RVA strains in China 1142:1180 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 7 1 contain possess 1194:1200 arg2 site 1234:1237 an extra N-linked glycosylation site 1202:1237 an extra N-linked glycosylation site compared with the G3 strain of RotaTeq 1202:1276 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 4 2 theme strains 766:772 arg1 VP4 730:732 VP4 730:732 VP4 730:732 In this study, we sequenced viral protein VP7 and VP4 outer capsid proteins of 50 RVA strains circulating in China from 2016 to 2019. 36004332 4 2 theme strains 766:772 arg1 VP7 722:724 viral protein VP7 708:724 viral protein VP7 708:724 In this study, we sequenced viral protein VP7 and VP4 outer capsid proteins of 50 RVA strains circulating in China from 2016 to 2019. 36004332 11 3 from surveillance 1785:1796 arg1 RVAs 1837:1840 prevalent RVAs 1827:1840 prevalent RVAs 1827:1840 More genetic surveillance with antigenic evaluation in prevalent RVAs is necessary for developing and implementing rotavirus vaccines in China. 36004332 10 4 theme P[6 1727:1729 arg1 genotypes 1732:1740 G4 and P[6] genotypes 1720:1740 G4 and P[6] genotypes 1720:1740 Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. 36004332 6 5 theme P 1102:1102 arg1 genotypes 1104:1112 the G and P genotypes 1092:1112 the G and P genotypes of these strains 1092:1129 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 1 6 theme common 232:237 arg1 rotaviruses 200:210 Group A rotaviruses 192:210 Group A rotaviruses (RVAs) 192:217 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 1 6 theme common 232:237 arg1 agents 251:256 the most common etiological agents 223:256 the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide 223:324 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 4 7 theme outer 734:738 arg1 proteins 747:754 outer capsid proteins 734:754 outer capsid proteins 734:754 In this study, we sequenced viral protein VP7 and VP4 outer capsid proteins of 50 RVA strains circulating in China from 2016 to 2019. 36004332 10 8 theme G4 1720:1721 arg1 genotypes 1732:1740 G4 and P[6] genotypes 1720:1740 G4 and P[6] genotypes 1720:1740 Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. 36004332 6 9 theme G 1096:1096 arg1 genotypes 1104:1112 the G and P genotypes 1092:1112 the G and P genotypes of these strains 1092:1129 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 7 10 theme glycosylation 1220:1232 arg1 site 1234:1237 an extra N-linked glycosylation site 1202:1237 an extra N-linked glycosylation site compared with the G3 strain of RotaTeq 1202:1276 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 3 11 theme circulating 642:652 arg1 RVAs 654:657 circulating RVAs 642:657 circulating RVAs 642:657 Although RVA vaccines can provide homotypic and partially heterotypic protection against several strains, it is necessary to explore the genetic and antigenic variations between circulating RVAs and vaccine strains. 36004332 5 12 theme vaccine 933:939 arg1 strains 941:947 vaccine strains 933:947 vaccine strains of the same genotype 933:968 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 11 13 theme antigenic 1803:1811 arg1 evaluation 1813:1822 antigenic evaluation 1803:1822 antigenic evaluation 1803:1822 More genetic surveillance with antigenic evaluation in prevalent RVAs is necessary for developing and implementing rotavirus vaccines in China. 36004332 4 14 dep VP7 722:724 arg1 proteins 747:754 outer capsid proteins 734:754 outer capsid proteins 734:754 In this study, we sequenced viral protein VP7 and VP4 outer capsid proteins of 50 RVA strains circulating in China from 2016 to 2019. 36004332 9 15 theme strains 1506:1512 arg1 selection 1493:1501 the selection 1489:1501 the selection of strains that escape the RVA neutralizing-antibody pressure imposed by vaccines 1489:1583 These variations in antigenic sites might result in the selection of strains that escape the RVA neutralizing-antibody pressure imposed by vaccines. 36004332 7 16 theme extra 1205:1209 arg1 site 1234:1237 an extra N-linked glycosylation site 1202:1237 an extra N-linked glycosylation site compared with the G3 strain of RotaTeq 1202:1276 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 10 17 theme P[6 1610:1612 arg1 genotypes 1615:1623 the G4 and P[6] genotypes 1599:1623 genotypes 1615:1623 Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. 36004332 1 18 theme A 198:198 arg1 RVAs 213:216 RVAs 213:216 RVAs 213:216 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 1 18 theme A 198:198 arg1 rotaviruses 200:210 Group A rotaviruses 192:210 Group A rotaviruses (RVAs) 192:217 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 1 18 theme A 198:198 arg1 agents 251:256 the most common etiological agents 223:256 the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide 223:324 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 5 19 theme reported 906:913 arg1 strains 921:927 previously reported human strains 895:927 previously reported human strains 895:927 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 9 20 theme antigenic 1457:1465 arg1 sites 1467:1471 antigenic sites 1457:1471 antigenic sites 1457:1471 These variations in antigenic sites might result in the selection of strains that escape the RVA neutralizing-antibody pressure imposed by vaccines. 36004332 9 21 theme RVA 1530:1532 arg1 pressure 1556:1563 the RVA neutralizing-antibody pressure 1526:1563 the RVA neutralizing-antibody pressure imposed by vaccines 1526:1583 These variations in antigenic sites might result in the selection of strains that escape the RVA neutralizing-antibody pressure imposed by vaccines. 36004332 8 22 theme N-linked 1293:1300 arg1 site 1316:1319 The potential N-linked glycosylation site 1279:1319 The potential N-linked glycosylation site at residues 69-71 1279:1337 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 6 23 theme strains 1123:1129 arg1 genotypes 1104:1112 the G and P genotypes 1092:1112 the G and P genotypes of these strains 1092:1129 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 3 24 theme heterotypic 522:532 arg1 protection 534:543 homotypic and partially heterotypic protection 498:543 homotypic and partially heterotypic protection against several strains 498:567 Although RVA vaccines can provide homotypic and partially heterotypic protection against several strains, it is necessary to explore the genetic and antigenic variations between circulating RVAs and vaccine strains. 36004332 6 25 theme amino 1044:1048 arg1 variations 1055:1064 multiple amino acid variations 1035:1064 multiple amino acid variations 1035:1064 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 0 26 theme circulating 55:65 arg1 strains 83:89 circulating human rotavirus strains 55:89 circulating human rotavirus strains 55:89 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 27 theme antigenic 142:150 arg1 epitopes 152:159 their antigenic epitopes 136:159 their antigenic epitopes 136:159 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 28 theme rotavirus 73:81 arg1 strains 83:89 circulating human rotavirus strains 55:89 circulating human rotavirus strains 55:89 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 2 29 dep RotaTeq 392:398 arg1 G6 408:409 G6 408:409 G6 408:409 At present, two live-attenuated RVA vaccines, LLR (G10P[15]) and RotaTeq (G1-G4, G6 P[8], P[5]), have been introduced to mainland China. 36004332 4 30 dep 2019 808:811 arg1 to 805:806 to 805:806 to 805:806 In this study, we sequenced viral protein VP7 and VP4 outer capsid proteins of 50 RVA strains circulating in China from 2016 to 2019. 36004332 5 31 theme same 956:959 arg1 genotype 961:968 the same genotype 952:968 the same genotype 952:968 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 7 32 from strains 1165:1171 arg1 China 1176:1180 China 1176:1180 China 1176:1180 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 0 33 from VP4/VP7 44:50 arg1 China 94:98 China 94:98 China from 2016 to 2019 94:116 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 33 from VP4/VP7 44:50 arg1 2019 113:116 2019 113:116 2019 113:116 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 2 34 theme RVA 359:361 arg1 LLR 373:375 LLR 373:375 LLR (G10P[15]) 373:386 At present, two live-attenuated RVA vaccines, LLR (G10P[15]) and RotaTeq (G1-G4, G6 P[8], P[5]), have been introduced to mainland China. 36004332 2 34 theme RVA 359:361 arg1 RotaTeq 392:398 RotaTeq 392:398 RotaTeq 392:398 At present, two live-attenuated RVA vaccines, LLR (G10P[15]) and RotaTeq (G1-G4, G6 P[8], P[5]), have been introduced to mainland China. 36004332 2 34 theme RVA 359:361 arg1 vaccines 363:370 two live-attenuated RVA vaccines 339:370 two live-attenuated RVA vaccines 339:370 At present, two live-attenuated RVA vaccines, LLR (G10P[15]) and RotaTeq (G1-G4, G6 P[8], P[5]), have been introduced to mainland China. 36004332 8 35 dep residues 1324:1331 arg1 69-71 1333:1337 69-71 1333:1337 69-71 1333:1337 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 5 36 theme all 850:852 arg1 strains 854:860 almost all strains 843:860 almost all strains 843:860 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 7 37 theme RVA 1161:1163 arg1 strains 1165:1171 all circulating G3 RVA strains 1142:1171 all circulating G3 RVA strains in China 1142:1180 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 8 38 theme G9 1356:1357 arg1 strains 1359:1365 all G9 strains 1352:1365 all G9 strains 1352:1365 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 0 39 theme Phylogenetic 0:11 arg1 analysis 13:20 Phylogenetic analysis 0:20 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 0:190 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 1 40 theme etiological 239:249 arg1 rotaviruses 200:210 Group A rotaviruses 192:210 Group A rotaviruses (RVAs) 192:217 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 1 40 theme etiological 239:249 arg1 agents 251:256 the most common etiological agents 223:256 the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide 223:324 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 5 41 theme VP7 818:820 arg1 sequences 830:838 The VP7 and VP4 sequences 814:838 The VP7 and VP4 sequences of almost all strains 814:860 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 7 42 theme circulating 1146:1156 arg1 strains 1165:1171 all circulating G3 RVA strains 1142:1171 all circulating G3 RVA strains in China 1142:1180 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 8 43 from residues 1324:1331 arg1 site 1316:1319 The potential N-linked glycosylation site 1279:1319 The potential N-linked glycosylation site at residues 69-71 1279:1337 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 5 44 theme VP4 826:828 arg1 sequences 830:838 The VP7 and VP4 sequences 814:838 The VP7 and VP4 sequences of almost all strains 814:860 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 4 45 theme protein 714:720 arg1 VP7 722:724 viral protein VP7 708:724 viral protein VP7 708:724 In this study, we sequenced viral protein VP7 and VP4 outer capsid proteins of 50 RVA strains circulating in China from 2016 to 2019. 36004332 0 46 theme viral 29:33 arg1 proteins 35:42 the viral proteins 25:42 the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains 25:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 46 theme viral 29:33 arg1 comparison 122:131 comparison 122:131 comparison of their antigenic epitopes with those of vaccine strains 122:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 46 theme viral 29:33 arg1 VP4/VP7 44:50 VP4/VP7 44:50 VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 44:116 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 1 47 theme acute 268:272 arg1 diarrhea 274:281 severe acute diarrhea 261:281 severe acute diarrhea 261:281 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 8 48 link N-linked 1293:1300 arg1 site 1316:1319 The potential N-linked glycosylation site 1279:1319 The potential N-linked glycosylation site at residues 69-71 1279:1337 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 11 49 with surveillance 1785:1796 arg1 evaluation 1813:1822 antigenic evaluation 1803:1822 antigenic evaluation 1803:1822 More genetic surveillance with antigenic evaluation in prevalent RVAs is necessary for developing and implementing rotavirus vaccines in China. 36004332 2 50 dep G6 408:409 arg1 P[5 417:419 P[5 417:419 P[5 417:419 At present, two live-attenuated RVA vaccines, LLR (G10P[15]) and RotaTeq (G1-G4, G6 P[8], P[5]), have been introduced to mainland China. 36004332 6 51 located found 1071:1075 arg2 variations 1055:1064 multiple amino acid variations 1035:1064 multiple amino acid variations 1035:1064 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 6 51 located found 1071:1075 arg1 epitopes 1006:1013 the presumed antigenic epitopes 983:1013 the presumed antigenic epitopes of the VP7 and VP4 983:1032 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 10 52 theme porcine 1672:1678 arg1 strains 1680:1686 porcine strains 1672:1686 porcine strains 1672:1686 Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. 36004332 7 53 theme G3 1257:1258 arg1 strain 1260:1265 the G3 strain 1253:1265 the G3 strain of RotaTeq 1253:1276 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 0 54 with VP4/VP7 44:50 arg1 those 166:170 those 166:170 those 166:170 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 8 55 theme Rotavac 1408:1414 arg1 vaccine 1428:1434 the Rotavac or Rotasill vaccine 1404:1434 vaccine 1428:1434 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 3 56 theme genetic 601:607 arg1 variations 623:632 the genetic and antigenic variations 597:632 the genetic and antigenic variations between circulating RVAs and vaccine strains 597:677 Although RVA vaccines can provide homotypic and partially heterotypic protection against several strains, it is necessary to explore the genetic and antigenic variations between circulating RVAs and vaccine strains. 36004332 7 57 gly glycosylation 1220:1232 arg2 site 1234:1237 an extra N-linked glycosylation site 1202:1237 an extra N-linked glycosylation site compared with the G3 strain of RotaTeq 1202:1276 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 8 58 theme Rotasill 1419:1426 arg1 vaccine 1428:1434 the Rotavac or Rotasill vaccine 1404:1434 vaccine 1428:1434 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 0 59 theme vaccine 175:181 arg1 strains 183:189 vaccine strains 175:189 vaccine strains 175:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 11 60 theme genetic 1777:1783 arg1 surveillance 1785:1796 More genetic surveillance 1772:1796 More genetic surveillance with antigenic evaluation in prevalent RVAs 1772:1840 More genetic surveillance with antigenic evaluation in prevalent RVAs is necessary for developing and implementing rotavirus vaccines in China. 36004332 4 61 theme RVA 762:764 arg1 strains 766:772 50 RVA strains 759:772 50 RVA strains circulating in China from 2016 to 2019 759:811 In this study, we sequenced viral protein VP7 and VP4 outer capsid proteins of 50 RVA strains circulating in China from 2016 to 2019. 36004332 6 62 theme VP4 1030:1032 arg1 epitopes 1006:1013 the presumed antigenic epitopes 983:1013 the presumed antigenic epitopes of the VP7 and VP4 983:1032 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 7 63 theme RotaTeq 1270:1276 arg1 strain 1260:1265 the G3 strain 1253:1265 the G3 strain of RotaTeq 1253:1276 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 6 64 theme VP7 1022:1024 arg1 epitopes 1006:1013 the presumed antigenic epitopes 983:1013 the presumed antigenic epitopes of the VP7 and VP4 983:1032 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 3 65 theme antigenic 613:621 arg1 variations 623:632 the genetic and antigenic variations 597:632 the genetic and antigenic variations between circulating RVAs and vaccine strains 597:677 Although RVA vaccines can provide homotypic and partially heterotypic protection against several strains, it is necessary to explore the genetic and antigenic variations between circulating RVAs and vaccine strains. 36004332 4 66 theme capsid 740:745 arg1 proteins 747:754 outer capsid proteins 734:754 outer capsid proteins 734:754 In this study, we sequenced viral protein VP7 and VP4 outer capsid proteins of 50 RVA strains circulating in China from 2016 to 2019. 36004332 3 67 theme vaccine 663:669 arg1 strains 671:677 vaccine strains 663:677 vaccine strains 663:677 Although RVA vaccines can provide homotypic and partially heterotypic protection against several strains, it is necessary to explore the genetic and antigenic variations between circulating RVAs and vaccine strains. 36004332 6 68 theme antigenic 996:1004 arg1 epitopes 1006:1013 the presumed antigenic epitopes 983:1013 the presumed antigenic epitopes of the VP7 and VP4 983:1032 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 6 69 dep VP7 1022:1024 arg1 the 1018:1020 the 1018:1020 the 1018:1020 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 1 70 theme Group 192:196 arg1 RVAs 213:216 RVAs 213:216 RVAs 213:216 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 1 70 theme Group 192:196 arg1 rotaviruses 200:210 Group A rotaviruses 192:210 Group A rotaviruses (RVAs) 192:217 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 1 70 theme Group 192:196 arg1 agents 251:256 the most common etiological agents 223:256 the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide 223:324 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 8 71 theme potential 1283:1291 arg1 site 1316:1319 The potential N-linked glycosylation site 1279:1319 The potential N-linked glycosylation site at residues 69-71 1279:1337 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 7 72 theme N-linked 1211:1218 arg1 site 1234:1237 an extra N-linked glycosylation site 1202:1237 an extra N-linked glycosylation site compared with the G3 strain of RotaTeq 1202:1276 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 8 73 theme G9 1391:1392 arg1 strain 1394:1399 the G9 strain 1387:1399 the G9 strain of the Rotavac or Rotasill vaccine 1387:1434 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 9 74 theme neutralizing-antibody 1534:1554 arg1 pressure 1556:1563 the RVA neutralizing-antibody pressure 1526:1563 the RVA neutralizing-antibody pressure imposed by vaccines 1526:1583 These variations in antigenic sites might result in the selection of strains that escape the RVA neutralizing-antibody pressure imposed by vaccines. 36004332 11 75 from vaccines 1897:1904 arg1 China 1909:1913 China 1909:1913 China 1909:1913 More genetic surveillance with antigenic evaluation in prevalent RVAs is necessary for developing and implementing rotavirus vaccines in China. 36004332 3 76 theme RVA 473:475 arg1 vaccines 477:484 RVA vaccines 473:484 RVA vaccines 473:484 Although RVA vaccines can provide homotypic and partially heterotypic protection against several strains, it is necessary to explore the genetic and antigenic variations between circulating RVAs and vaccine strains. 36004332 9 77 from variations 1443:1452 arg1 sites 1467:1471 antigenic sites 1457:1471 antigenic sites 1457:1471 These variations in antigenic sites might result in the selection of strains that escape the RVA neutralizing-antibody pressure imposed by vaccines. 36004332 8 78 theme glycosylation 1302:1314 arg1 site 1316:1319 The potential N-linked glycosylation site 1279:1319 The potential N-linked glycosylation site at residues 69-71 1279:1337 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 0 79 with comparison 122:131 arg1 those 166:170 those 166:170 those 166:170 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 80 theme epitopes 152:159 arg1 proteins 35:42 the viral proteins 25:42 the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains 25:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 80 theme epitopes 152:159 arg1 comparison 122:131 comparison 122:131 comparison of their antigenic epitopes with those of vaccine strains 122:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 80 theme epitopes 152:159 arg1 VP4/VP7 44:50 VP4/VP7 44:50 VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 44:116 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 5 81 theme human 915:919 arg1 strains 921:927 previously reported human strains 895:927 previously reported human strains 895:927 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 2 82 theme mainland 448:455 arg1 China 457:461 mainland China 448:461 mainland China 448:461 At present, two live-attenuated RVA vaccines, LLR (G10P[15]) and RotaTeq (G1-G4, G6 P[8], P[5]), have been introduced to mainland China. 36004332 6 83 theme acid 1050:1053 arg1 variations 1055:1064 multiple amino acid variations 1035:1064 multiple amino acid variations 1035:1064 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 0 84 theme human 67:71 arg1 strains 83:89 circulating human rotavirus strains 55:89 circulating human rotavirus strains 55:89 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 3 85 theme homotypic 498:506 arg1 protection 534:543 homotypic and partially heterotypic protection 498:543 homotypic and partially heterotypic protection against several strains 498:567 Although RVA vaccines can provide homotypic and partially heterotypic protection against several strains, it is necessary to explore the genetic and antigenic variations between circulating RVAs and vaccine strains. 36004332 6 86 theme multiple 1035:1042 arg1 variations 1055:1064 multiple amino acid variations 1035:1064 multiple amino acid variations 1035:1064 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 0 87 theme strains 83:89 arg1 proteins 35:42 the viral proteins 25:42 the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains 25:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 87 theme strains 83:89 arg1 comparison 122:131 comparison 122:131 comparison of their antigenic epitopes with those of vaccine strains 122:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 87 theme strains 83:89 arg1 VP4/VP7 44:50 VP4/VP7 44:50 VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 44:116 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 10 88 theme genotypes 1732:1740 arg1 transmission 1704:1715 the transmission 1700:1715 the transmission of G4 and P[6] genotypes from pigs to humans in China 1700:1769 Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. 36004332 0 89 dep 2019 113:116 arg1 to 110:111 to 110:111 to 110:111 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 1 90 theme old 312:314 arg1 worldwide 316:324 5 years old worldwide 304:324 5 years old worldwide 304:324 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 10 91 from pigs 1747:1750 arg1 transmission 1704:1715 the transmission 1700:1715 the transmission of G4 and P[6] genotypes from pigs to humans in China 1700:1769 Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. 36004332 5 92 theme genotype 961:968 arg1 strains 921:927 previously reported human strains 895:927 previously reported human strains 895:927 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 5 92 theme genotype 961:968 arg1 strains 941:947 vaccine strains 933:947 vaccine strains of the same genotype 933:968 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 10 93 from humans 1755:1760 arg1 China 1765:1769 China 1765:1769 China 1765:1769 Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. 36004332 8 94 gly glycosylation 1302:1314 arg2 residues 1324:1331 residues 69-71 1324:1337 residues 69-71 1324:1337 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 8 94 gly glycosylation 1302:1314 arg2 site 1316:1319 The potential N-linked glycosylation site 1279:1319 The potential N-linked glycosylation site at residues 69-71 1279:1337 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 10 95 from G4 1603:1604 arg1 study 1633:1637 this study 1628:1637 this study 1628:1637 Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. 36004332 7 96 theme G3 1158:1159 arg1 strains 1165:1171 all circulating G3 RVA strains 1142:1171 all circulating G3 RVA strains in China 1142:1180 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 2 97 theme live-attenuated 343:357 arg1 LLR 373:375 LLR 373:375 LLR (G10P[15]) 373:386 At present, two live-attenuated RVA vaccines, LLR (G10P[15]) and RotaTeq (G1-G4, G6 P[8], P[5]), have been introduced to mainland China. 36004332 2 97 theme live-attenuated 343:357 arg1 RotaTeq 392:398 RotaTeq 392:398 RotaTeq 392:398 At present, two live-attenuated RVA vaccines, LLR (G10P[15]) and RotaTeq (G1-G4, G6 P[8], P[5]), have been introduced to mainland China. 36004332 2 97 theme live-attenuated 343:357 arg1 vaccines 363:370 two live-attenuated RVA vaccines 339:370 two live-attenuated RVA vaccines 339:370 At present, two live-attenuated RVA vaccines, LLR (G10P[15]) and RotaTeq (G1-G4, G6 P[8], P[5]), have been introduced to mainland China. 36004332 8 98 located found 1343:1347 arg2 site 1316:1319 The potential N-linked glycosylation site 1279:1319 The potential N-linked glycosylation site at residues 69-71 1279:1337 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 8 98 located found 1343:1347 arg1 China 1370:1374 China 1370:1374 China 1370:1374 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 8 98 located found 1343:1347 arg1 strains 1359:1365 all G9 strains 1352:1365 all G9 strains 1352:1365 The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. 36004332 11 99 theme prevalent 1827:1835 arg1 RVAs 1837:1840 prevalent RVAs 1827:1840 prevalent RVAs 1827:1840 More genetic surveillance with antigenic evaluation in prevalent RVAs is necessary for developing and implementing rotavirus vaccines in China. 36004332 10 100 from genotypes 1615:1623 arg1 study 1633:1637 this study 1628:1637 this study 1628:1637 Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. 36004332 3 101 theme several 553:559 arg1 strains 561:567 several strains 553:567 several strains 553:567 Although RVA vaccines can provide homotypic and partially heterotypic protection against several strains, it is necessary to explore the genetic and antigenic variations between circulating RVAs and vaccine strains. 36004332 0 102 theme proteins 35:42 arg1 analysis 13:20 Phylogenetic analysis 0:20 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 0:190 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 1 103 theme severe 261:266 arg1 diarrhea 274:281 severe acute diarrhea 261:281 severe acute diarrhea 261:281 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 10 104 theme high 1646:1649 arg1 homology 1651:1658 high homology 1646:1658 high homology to those of porcine strains 1646:1686 Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. 36004332 4 105 theme viral 708:712 arg1 VP7 722:724 viral protein VP7 708:724 viral protein VP7 708:724 In this study, we sequenced viral protein VP7 and VP4 outer capsid proteins of 50 RVA strains circulating in China from 2016 to 2019. 36004332 1 106 theme diarrhea 274:281 arg1 rotaviruses 200:210 Group A rotaviruses 192:210 Group A rotaviruses (RVAs) 192:217 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 1 106 theme diarrhea 274:281 arg1 agents 251:256 the most common etiological agents 223:256 the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide 223:324 Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. 36004332 11 107 theme rotavirus 1887:1895 arg1 vaccines 1897:1904 rotavirus vaccines 1887:1904 rotavirus vaccines in China 1887:1913 More genetic surveillance with antigenic evaluation in prevalent RVAs is necessary for developing and implementing rotavirus vaccines in China. 36004332 0 108 dep proteins 35:42 arg1 proteins 35:42 the viral proteins 25:42 the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains 25:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 108 dep proteins 35:42 arg1 comparison 122:131 comparison 122:131 comparison of their antigenic epitopes with those of vaccine strains 122:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 108 dep proteins 35:42 arg1 VP4/VP7 44:50 VP4/VP7 44:50 VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 44:116 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 6 109 theme presumed 987:994 arg1 epitopes 1006:1013 the presumed antigenic epitopes 983:1013 the presumed antigenic epitopes of the VP7 and VP4 983:1032 However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. 36004332 7 110 link N-linked 1211:1218 arg1 site 1234:1237 an extra N-linked glycosylation site 1202:1237 an extra N-linked glycosylation site compared with the G3 strain of RotaTeq 1202:1276 Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. 36004332 5 111 theme strains 854:860 arg1 sequences 830:838 The VP7 and VP4 sequences 814:838 The VP7 and VP4 sequences of almost all strains 814:860 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 0 112 from comparison 122:131 arg1 China 94:98 China 94:98 China from 2016 to 2019 94:116 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 112 from comparison 122:131 arg1 2019 113:116 2019 113:116 2019 113:116 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 5 113 theme high 869:872 arg1 homology 874:881 high homology 869:881 high homology to those of previously reported human strains and vaccine strains of the same genotype 869:968 The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. 36004332 0 114 from 2019 113:116 arg1 China 94:98 China 94:98 China from 2016 to 2019 94:116 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 114 from 2019 113:116 arg1 comparison 122:131 comparison 122:131 comparison of their antigenic epitopes with those of vaccine strains 122:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 114 from 2019 113:116 arg1 VP4/VP7 44:50 VP4/VP7 44:50 VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 44:116 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 36004332 0 114 from 2019 113:116 arg1 proteins 35:42 the viral proteins 25:42 the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains 25:189 Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. 35874007 9 0 theme α1,6-mannose-exposed 1657:1676 arg1 N-glycans 1678:1686 α1,6-mannose-exposed N-glycans 1657:1686 α1,6-mannose-exposed N-glycans 1657:1686 Simultaneous elimination of AtEDEM1 and AtEDEM2 completely blocks generation of α1,6-mannose-exposed N-glycans on bri1-5, while overexpression of either AtEDEM1 or AtEDEM2 stimulates bri1-5 ERAD and enhances the bri1-5 dwarfism. 35874007 7 1 theme bri1-5 1466:1471 arg1 degradation 1473:1483 bri1-5 degradation 1466:1483 bri1-5 degradation 1466:1483 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 4 2 theme Arabidopsis 879:889 arg1 homologs 901:908 the Arabidopsis Htm1/EDEM homologs 875:908 the Arabidopsis Htm1/EDEM homologs 875:908 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 6 3 theme free 1193:1196 arg1 residue 1211:1217 a different free α1,6-mannose residue 1181:1217 a different free α1,6-mannose residue 1181:1217 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 7 4 theme irb1-1 1456:1461 arg1 effect 1446:1451 the inhibitory effect 1431:1451 the inhibitory effect of irb1-1 on bri1-5 degradation 1431:1483 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 4 5 theme Htm1/EDEM 891:899 arg1 homologs 901:908 the Arabidopsis Htm1/EDEM homologs 875:908 the Arabidopsis Htm1/EDEM homologs 875:908 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 1 6 theme key 210:212 arg1 process 223:229 a key cellular process 208:229 a key cellular process for degrading misfolded proteins 208:262 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 1 6 theme key 210:212 arg1 degradation 186:196 Endoplasmic reticulum-associated degradation 153:196 Endoplasmic reticulum-associated degradation (ERAD) 153:203 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 0 7 theme Degradation 132:142 arg1 Process 144:150 an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 84:150 an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 84:150 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 35874007 3 8 theme Arabidopsis 555:565 arg1 homologs 567:574 two Arabidopsis homologs 551:574 two Arabidopsis homologs of Htm1/EDEMs 551:588 An earlier study suggested that two Arabidopsis homologs of Htm1/EDEMs function redundantly in generating such a conserved N-glycan signal. 35874007 2 9 link -linked 305:311 arg1 signal 378:383 a critical ERAD signal 362:383 a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals 362:516 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 9 link -linked 305:311 arg1 glycan 313:318 an asparagine (N)-linked glycan 288:318 an asparagine (N)-linked glycan containing a free α1,6-mannose residue 288:357 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 6 10 with glycosylation 1135:1147 arg1 glycans 1164:1170 truncated glycans 1154:1170 truncated glycans carrying a different free α1,6-mannose residue 1154:1217 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 4 11 theme homologs 901:908 arg1 AtEDEM1 911:917 AtEDEM1 911:917 AtEDEM1 911:917 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 11 theme homologs 901:908 arg1 homologs 901:908 the Arabidopsis Htm1/EDEM homologs 875:908 the Arabidopsis Htm1/EDEM homologs 875:908 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 11 theme homologs 901:908 arg1 one 868:870 one 868:870 one 868:870 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 12 theme bri1 713:716 arg1 reversal 701:708 reversal 701:708 reversal of bri1 701:716 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 3 13 theme conserved 632:640 arg1 signal 651:656 such a conserved N-glycan signal 625:656 such a conserved N-glycan signal 625:656 An earlier study suggested that two Arabidopsis homologs of Htm1/EDEMs function redundantly in generating such a conserved N-glycan signal. 35874007 1 14 theme Endoplasmic 153:163 arg1 process 223:229 a key cellular process 208:229 a key cellular process for degrading misfolded proteins 208:262 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 1 14 theme Endoplasmic 153:163 arg1 degradation 186:196 Endoplasmic reticulum-associated degradation 153:196 Endoplasmic reticulum-associated degradation (ERAD) 153:203 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 1 14 theme Endoplasmic 153:163 arg1 ERAD 199:202 ERAD 199:202 ERAD 199:202 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 7 15 theme Htm1/EDEM 1350:1358 arg1 mutation 1319:1326 an insertional mutation 1304:1326 an insertional mutation in AtEDEM2 1304:1337 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 7 15 theme Htm1/EDEM 1350:1358 arg1 homolog 1360:1366 the other Htm1/EDEM homolog 1340:1366 the other Htm1/EDEM homolog 1340:1366 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 4 16 theme irb1 695:698 arg1 defective 855:863 defective 855:863 defective 855:863 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 16 theme irb1 695:698 arg1 mutants 719:725 the Arabidopsis irb1 (reversal of bri1) mutants 679:725 the Arabidopsis irb1 (reversal of bri1) mutants 679:725 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 0 17 theme Rate-Limiting 46:58 arg1 Step 76:79 a Rate-Limiting Demannosylation Step 44:79 a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 44:150 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 35874007 9 18 theme bri1-5 1789:1794 arg1 dwarfism 1796:1803 the bri1-5 dwarfism 1785:1803 the bri1-5 dwarfism 1785:1803 Simultaneous elimination of AtEDEM1 and AtEDEM2 completely blocks generation of α1,6-mannose-exposed N-glycans on bri1-5, while overexpression of either AtEDEM1 or AtEDEM2 stimulates bri1-5 ERAD and enhances the bri1-5 dwarfism. 35874007 8 19 theme AtEDEM2 1496:1502 arg1 transgenes 1504:1513 AtEDEM2 transgenes 1496:1513 AtEDEM2 transgenes 1496:1513 Moreover, AtEDEM2 transgenes rescued the irb1-1 mutation with lower efficacy than AtEDEM1. 35874007 9 20 from generation 1643:1652 arg1 bri1-5 1691:1696 bri1-5 1691:1696 bri1-5 1691:1696 Simultaneous elimination of AtEDEM1 and AtEDEM2 completely blocks generation of α1,6-mannose-exposed N-glycans on bri1-5, while overexpression of either AtEDEM1 or AtEDEM2 stimulates bri1-5 ERAD and enhances the bri1-5 dwarfism. 35874007 2 21 theme Homologous 396:405 arg1 EDEMs 500:504 EDEMs 500:504 EDEMs 500:504 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 21 theme Homologous 396:405 arg1 proteins 490:497 Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins 396:497 Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) 396:505 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 0 22 theme Endoplasmic 99:109 arg1 Process 144:150 an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 84:150 an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 84:150 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 35874007 6 23 theme Asparagine-Linked 1071:1087 arg1 Glycosylation 1089:1101 the Arabidopsis Asparagine-Linked Glycosylation 3 1055:1103 the Arabidopsis Asparagine-Linked Glycosylation 3 1055:1103 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 8 24 theme irb1-1 1527:1532 arg1 mutation 1534:1541 the irb1-1 mutation 1523:1541 the irb1-1 mutation 1523:1541 Moreover, AtEDEM2 transgenes rescued the irb1-1 mutation with lower efficacy than AtEDEM1. 35874007 5 25 theme wild-type 937:945 arg1 AtEDEM1 947:953 the wild-type AtEDEM1 933:953 the wild-type AtEDEM1 933:953 We show that the wild-type AtEDEM1, but not its catalytically inactive mutant, rescues irb1-1. 35874007 2 26 theme α-Mannosidase-like 471:488 arg1 EDEMs 500:504 EDEMs 500:504 EDEMs 500:504 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 26 theme α-Mannosidase-like 471:488 arg1 proteins 490:497 Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins 396:497 Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) 396:505 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 4 27 theme brassinosteroid 817:831 arg1 BRI1 842:845 the brassinosteroid receptor BRI1 813:845 the brassinosteroid receptor BRI1 813:845 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 0 28 theme AtEDEM1 22:28 arg1 Role 14:17 A Predominant Role 0:17 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 0:151 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 35874007 9 29 theme AtEDEM1 1605:1611 arg1 elimination 1590:1600 Simultaneous elimination 1577:1600 Simultaneous elimination of AtEDEM1 and AtEDEM2 1577:1623 Simultaneous elimination of AtEDEM1 and AtEDEM2 completely blocks generation of α1,6-mannose-exposed N-glycans on bri1-5, while overexpression of either AtEDEM1 or AtEDEM2 stimulates bri1-5 ERAD and enhances the bri1-5 dwarfism. 35874007 7 30 theme insertional 1307:1317 arg1 mutation 1319:1326 an insertional mutation 1304:1326 an insertional mutation in AtEDEM2 1304:1337 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 7 30 theme insertional 1307:1317 arg1 homolog 1360:1366 the other Htm1/EDEM homolog 1340:1366 the other Htm1/EDEM homolog 1340:1366 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 4 31 theme BRI1 842:845 arg1 variant 802:808 an ER-retained mutant variant 780:808 an ER-retained mutant variant of the brassinosteroid receptor BRI1 780:845 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 31 theme BRI1 842:845 arg1 1-5 766:768 1-5 766:768 1-5 766:768 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 9 32 theme AtEDEM2 1617:1623 arg1 elimination 1590:1600 Simultaneous elimination 1577:1600 Simultaneous elimination of AtEDEM1 and AtEDEM2 1577:1623 Simultaneous elimination of AtEDEM1 and AtEDEM2 completely blocks generation of α1,6-mannose-exposed N-glycans on bri1-5, while overexpression of either AtEDEM1 or AtEDEM2 stimulates bri1-5 ERAD and enhances the bri1-5 dwarfism. 35874007 7 33 from mutation 1319:1326 arg1 AtEDEM2 1331:1337 AtEDEM2 1331:1337 AtEDEM2 1331:1337 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 3 34 theme N-glycan 642:649 arg1 signal 651:656 such a conserved N-glycan signal 625:656 such a conserved N-glycan signal 625:656 An earlier study suggested that two Arabidopsis homologs of Htm1/EDEMs function redundantly in generating such a conserved N-glycan signal. 35874007 4 35 theme mutant 795:800 arg1 variant 802:808 an ER-retained mutant variant 780:808 an ER-retained mutant variant of the brassinosteroid receptor BRI1 780:845 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 35 theme mutant 795:800 arg1 1-5 766:768 1-5 766:768 1-5 766:768 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 2 36 theme free 333:336 arg1 residue 351:357 a free α1,6-mannose residue 331:357 a free α1,6-mannose residue 331:357 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 1 37 theme misfolded 245:253 arg1 proteins 255:262 misfolded proteins 245:262 misfolded proteins 245:262 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 2 38 from α-mannosidase 410:422 arg1 ER-Degradation 446:459 ER-Degradation 446:459 ER-Degradation 446:459 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 38 from α-mannosidase 410:422 arg1 yeast 436:440 yeast 436:440 yeast 436:440 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 39 theme ERAD 373:376 arg1 signal 378:383 a critical ERAD signal 362:383 a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals 362:516 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 39 theme ERAD 373:376 arg1 glycan 313:318 an asparagine (N)-linked glycan 288:318 an asparagine (N)-linked glycan containing a free α1,6-mannose residue 288:357 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 7 40 contain has 1369:1371 arg1 mutation 1319:1326 an insertional mutation 1304:1326 an insertional mutation in AtEDEM2 1304:1337 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 7 40 contain has 1369:1371 arg2 effect 1387:1392 no detectable effect 1373:1392 no detectable effect 1373:1392 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 7 40 contain has 1369:1371 arg1 homolog 1360:1366 the other Htm1/EDEM homolog 1340:1366 the other Htm1/EDEM homolog 1340:1366 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 9 41 theme N-glycans 1678:1686 arg1 generation 1643:1652 generation 1643:1652 generation of α1,6-mannose-exposed N-glycans on bri1-5 1643:1696 Simultaneous elimination of AtEDEM1 and AtEDEM2 completely blocks generation of α1,6-mannose-exposed N-glycans on bri1-5, while overexpression of either AtEDEM1 or AtEDEM2 stimulates bri1-5 ERAD and enhances the bri1-5 dwarfism. 35874007 6 42 theme different 1183:1191 arg1 residue 1211:1217 a different free α1,6-mannose residue 1181:1217 a different free α1,6-mannose residue 1181:1217 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 3 43 theme earlier 522:528 arg1 study 530:534 An earlier study 519:534 An earlier study 519:534 An earlier study suggested that two Arabidopsis homologs of Htm1/EDEMs function redundantly in generating such a conserved N-glycan signal. 35874007 7 44 theme inhibitory 1435:1444 arg1 effect 1446:1451 the inhibitory effect 1431:1451 the inhibitory effect of irb1-1 on bri1-5 degradation 1431:1483 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 6 45 theme irb1-1 1266:1271 arg1 effect 1256:1261 the inhibitory effect 1241:1261 the inhibitory effect of irb1-1 on bri1-5 ERAD 1241:1286 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 7 46 from effect 1446:1451 arg1 degradation 1473:1483 bri1-5 degradation 1466:1483 bri1-5 degradation 1466:1483 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 6 47 theme truncated 1154:1162 arg1 glycans 1164:1170 truncated glycans 1154:1170 truncated glycans carrying a different free α1,6-mannose residue 1154:1217 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 0 48 theme Process 144:150 arg1 Step 76:79 a Rate-Limiting Demannosylation Step 44:79 a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 44:150 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 35874007 2 49 theme -linked 305:311 arg1 signal 378:383 a critical ERAD signal 362:383 a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals 362:516 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 49 theme -linked 305:311 arg1 glycan 313:318 an asparagine (N)-linked glycan 288:318 an asparagine (N)-linked glycan containing a free α1,6-mannose residue 288:357 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 1 50 theme cellular 214:221 arg1 process 223:229 a key cellular process 208:229 a key cellular process for degrading misfolded proteins 208:262 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 1 50 theme cellular 214:221 arg1 degradation 186:196 Endoplasmic reticulum-associated degradation 153:196 Endoplasmic reticulum-associated degradation (ERAD) 153:203 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 9 51 theme AtEDEM1 1730:1736 arg1 overexpression 1705:1718 overexpression 1705:1718 overexpression of either AtEDEM1 or AtEDEM2 1705:1747 Simultaneous elimination of AtEDEM1 and AtEDEM2 completely blocks generation of α1,6-mannose-exposed N-glycans on bri1-5, while overexpression of either AtEDEM1 or AtEDEM2 stimulates bri1-5 ERAD and enhances the bri1-5 dwarfism. 35874007 10 52 theme functional 1837:1846 arg1 redundancy 1848:1857 its functional redundancy 1833:1857 its functional redundancy with AtEDEM2 1833:1870 We concluded that, despite its functional redundancy with AtEDEM2, AtEDEM1 plays a predominant role in promoting bri1-5 degradation. 35874007 9 53 theme AtEDEM2 1741:1747 arg1 overexpression 1705:1718 overexpression 1705:1718 overexpression of either AtEDEM1 or AtEDEM2 1705:1747 Simultaneous elimination of AtEDEM1 and AtEDEM2 completely blocks generation of α1,6-mannose-exposed N-glycans on bri1-5, while overexpression of either AtEDEM1 or AtEDEM2 stimulates bri1-5 ERAD and enhances the bri1-5 dwarfism. 35874007 6 54 theme inhibitory 1245:1254 arg1 effect 1256:1261 the inhibitory effect 1241:1261 the inhibitory effect of irb1-1 on bri1-5 ERAD 1241:1286 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 3 55 theme Htm1/EDEMs 579:588 arg1 homologs 567:574 two Arabidopsis homologs 551:574 two Arabidopsis homologs of Htm1/EDEMs 551:588 An earlier study suggested that two Arabidopsis homologs of Htm1/EDEMs function redundantly in generating such a conserved N-glycan signal. 35874007 9 56 theme bri1-5 1760:1765 arg1 ERAD 1767:1770 bri1-5 ERAD 1760:1770 bri1-5 ERAD 1760:1770 Simultaneous elimination of AtEDEM1 and AtEDEM2 completely blocks generation of α1,6-mannose-exposed N-glycans on bri1-5, while overexpression of either AtEDEM1 or AtEDEM2 stimulates bri1-5 ERAD and enhances the bri1-5 dwarfism. 35874007 7 57 theme detectable 1376:1385 arg1 effect 1387:1392 no detectable effect 1373:1392 no detectable effect 1373:1392 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 4 58 dep brassinosteroid-insensitive 738:764 arg1 1-5 766:768 1-5 766:768 1-5 766:768 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 58 dep brassinosteroid-insensitive 738:764 arg1 variant 802:808 an ER-retained mutant variant 780:808 an ER-retained mutant variant of the brassinosteroid receptor BRI1 780:845 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 58 dep brassinosteroid-insensitive 738:764 arg1 bri1-5 771:776 bri1-5 771:776 bri1-5 771:776 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 6 59 from effect 1256:1261 arg1 ERAD 1283:1286 bri1-5 ERAD 1276:1286 bri1-5 ERAD 1276:1286 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 0 60 theme Demannosylation 60:74 arg1 Step 76:79 a Rate-Limiting Demannosylation Step 44:79 a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 44:150 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 35874007 1 61 theme reticulum-associated 165:184 arg1 process 223:229 a key cellular process 208:229 a key cellular process for degrading misfolded proteins 208:262 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 1 61 theme reticulum-associated 165:184 arg1 degradation 186:196 Endoplasmic reticulum-associated degradation 153:196 Endoplasmic reticulum-associated degradation (ERAD) 153:203 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 1 61 theme reticulum-associated 165:184 arg1 ERAD 199:202 ERAD 199:202 ERAD 199:202 Endoplasmic reticulum-associated degradation (ERAD) is a key cellular process for degrading misfolded proteins. 35874007 6 62 theme α1,6-mannose 1198:1209 arg1 residue 1211:1217 a different free α1,6-mannose residue 1181:1217 a different free α1,6-mannose residue 1181:1217 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 4 63 theme Arabidopsis 683:693 arg1 irb1 695:698 Arabidopsis irb1 683:698 the Arabidopsis irb1 (reversal of bri1) mutants 679:725 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 0 64 theme Arabidopsis 87:97 arg1 Process 144:150 an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 84:150 an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 84:150 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 35874007 4 65 from one 868:870 arg1 defective 855:863 defective 855:863 defective 855:863 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 65 from one 868:870 arg1 mutants 719:725 the Arabidopsis irb1 (reversal of bri1) mutants 679:725 the Arabidopsis irb1 (reversal of bri1) mutants 679:725 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 0 66 theme Reticulum-Associated 111:130 arg1 Process 144:150 an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 84:150 an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process 84:150 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 35874007 4 67 from defective 855:863 arg1 AtEDEM1 911:917 AtEDEM1 911:917 AtEDEM1 911:917 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 67 from defective 855:863 arg1 homologs 901:908 the Arabidopsis Htm1/EDEM homologs 875:908 the Arabidopsis Htm1/EDEM homologs 875:908 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 67 from defective 855:863 arg1 one 868:870 one 868:870 one 868:870 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 68 dep irb1 695:698 arg1 reversal 701:708 reversal 701:708 reversal of bri1 701:716 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 6 69 theme Glycosylation 1089:1101 arg1 mutation 1043:1050 an insertional mutation 1028:1050 an insertional mutation 1028:1050 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 6 69 theme Glycosylation 1089:1101 arg1 ALG3 1106:1109 ALG3 1106:1109 ALG3 1106:1109 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 0 70 theme Predominant 2:12 arg1 Role 14:17 A Predominant Role 0:17 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 0:151 A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process. 35874007 6 71 theme Arabidopsis 1059:1069 arg1 Glycosylation 1089:1101 the Arabidopsis Asparagine-Linked Glycosylation 3 1055:1103 the Arabidopsis Asparagine-Linked Glycosylation 3 1055:1103 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 8 72 theme lower 1548:1552 arg1 efficacy 1554:1561 lower efficacy 1548:1561 lower efficacy than AtEDEM1 1548:1574 Moreover, AtEDEM2 transgenes rescued the irb1-1 mutation with lower efficacy than AtEDEM1. 35874007 9 73 theme Simultaneous 1577:1588 arg1 elimination 1590:1600 Simultaneous elimination 1577:1600 Simultaneous elimination of AtEDEM1 and AtEDEM2 1577:1623 Simultaneous elimination of AtEDEM1 and AtEDEM2 completely blocks generation of α1,6-mannose-exposed N-glycans on bri1-5, while overexpression of either AtEDEM1 or AtEDEM2 stimulates bri1-5 ERAD and enhances the bri1-5 dwarfism. 35874007 10 74 theme predominant 1889:1899 arg1 role 1901:1904 a predominant role 1887:1904 a predominant role 1887:1904 We concluded that, despite its functional redundancy with AtEDEM2, AtEDEM1 plays a predominant role in promoting bri1-5 degradation. 35874007 6 75 theme insertional 1031:1041 arg1 mutation 1043:1050 an insertional mutation 1028:1050 an insertional mutation 1028:1050 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 6 75 theme insertional 1031:1041 arg1 ALG3 1106:1109 ALG3 1106:1109 ALG3 1106:1109 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 2 76 theme Enhancing 461:469 arg1 EDEMs 500:504 EDEMs 500:504 EDEMs 500:504 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 76 theme Enhancing 461:469 arg1 proteins 490:497 Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins 396:497 Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) 396:505 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 6 77 link N-linked 1126:1133 arg1 glycosylation 1135:1147 N-linked glycosylation 1126:1147 N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue 1126:1217 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 6 78 theme N-linked 1126:1133 arg1 glycosylation 1135:1147 N-linked glycosylation 1126:1147 N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue 1126:1217 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 10 79 theme bri1-5 1919:1924 arg1 degradation 1926:1936 bri1-5 degradation 1919:1936 bri1-5 degradation 1919:1936 We concluded that, despite its functional redundancy with AtEDEM2, AtEDEM1 plays a predominant role in promoting bri1-5 degradation. 35874007 4 80 theme receptor 833:840 arg1 BRI1 842:845 the brassinosteroid receptor BRI1 813:845 the brassinosteroid receptor BRI1 813:845 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 2 81 theme α1,6-mannose 338:349 arg1 residue 351:357 a free α1,6-mannose residue 331:357 a free α1,6-mannose residue 331:357 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 82 contain containing 320:329 arg2 residue 351:357 a free α1,6-mannose residue 331:357 a free α1,6-mannose residue 331:357 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 82 contain containing 320:329 arg1 signal 378:383 a critical ERAD signal 362:383 a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals 362:516 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 82 contain containing 320:329 arg1 glycan 313:318 an asparagine (N)-linked glycan 288:318 an asparagine (N)-linked glycan containing a free α1,6-mannose residue 288:357 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 5 83 theme inactive 982:989 arg1 mutant 991:996 its catalytically inactive mutant 964:996 its catalytically inactive mutant 964:996 We show that the wild-type AtEDEM1, but not its catalytically inactive mutant, rescues irb1-1. 35874007 6 84 contain carrying 1172:1179 arg1 glycans 1164:1170 truncated glycans 1154:1170 truncated glycans carrying a different free α1,6-mannose residue 1154:1217 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 6 84 contain carrying 1172:1179 arg2 residue 1211:1217 a different free α1,6-mannose residue 1181:1217 a different free α1,6-mannose residue 1181:1217 Importantly, an insertional mutation of the Arabidopsis Asparagine-Linked Glycosylation 3 (ALG3), which causes N-linked glycosylation with truncated glycans carrying a different free α1,6-mannose residue, completely nullifies the inhibitory effect of irb1-1 on bri1-5 ERAD. 35874007 4 85 theme ER-retained 783:793 arg1 variant 802:808 an ER-retained mutant variant 780:808 an ER-retained mutant variant of the brassinosteroid receptor BRI1 780:845 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 4 85 theme ER-retained 783:793 arg1 1-5 766:768 1-5 766:768 1-5 766:768 Here we report that the Arabidopsis irb1 (reversal of bri1) mutants accumulate brassinosteroid-insensitive 1-5 (bri1-5), an ER-retained mutant variant of the brassinosteroid receptor BRI1 and are defective in one of the Arabidopsis Htm1/EDEM homologs, AtEDEM1. 35874007 7 86 theme other 1344:1348 arg1 mutation 1319:1326 an insertional mutation 1304:1326 an insertional mutation in AtEDEM2 1304:1337 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 7 86 theme other 1344:1348 arg1 homolog 1360:1366 the other Htm1/EDEM homolog 1340:1366 the other Htm1/EDEM homolog 1340:1366 Interestingly, an insertional mutation in AtEDEM2, the other Htm1/EDEM homolog, has no detectable effect on bri1-5 ERAD; however, it enhances the inhibitory effect of irb1-1 on bri1-5 degradation. 35874007 2 87 theme critical 364:371 arg1 signal 378:383 a critical ERAD signal 362:383 a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals 362:516 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 2 87 theme critical 364:371 arg1 glycan 313:318 an asparagine (N)-linked glycan 288:318 an asparagine (N)-linked glycan containing a free α1,6-mannose residue 288:357 It was well known that an asparagine (N)-linked glycan containing a free α1,6-mannose residue is a critical ERAD signal created by Homologous to α-mannosidase 1 (Htm1) in yeast and ER-Degradation Enhancing α-Mannosidase-like proteins (EDEMs) in mammals. 35874007 10 88 with redundancy 1848:1857 arg1 AtEDEM2 1864:1870 AtEDEM2 1864:1870 AtEDEM2 1864:1870 We concluded that, despite its functional redundancy with AtEDEM2, AtEDEM1 plays a predominant role in promoting bri1-5 degradation. 35684278 0 0 theme Antioxidant 69:79 arg1 Applications 99:110 Antioxidant and Antimicrobial Applications 69:110 Agricultural Products Safety: Antioxidant and Antimicrobial Applications 39:110 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 35684278 1 1 theme food 299:302 arg1 products 304:311 food products 299:311 food products 299:311 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 5 2 theme Antimicrobial 631:643 arg1 activity 645:652 Antimicrobial activity 631:652 Antimicrobial activity 631:652 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 9 3 dep lethality 1237:1245 arg1 apterus 1271:1277 apterus 1271:1277 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25% 1232:1303 Anti-insect activity was also strong, with 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25%. 35684278 9 3 dep lethality 1237:1245 arg1 nbsp 1266:1269 nbsp 1266:1269 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25% 1232:1303 Anti-insect activity was also strong, with 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25%. 35684278 3 4 theme volatile 455:462 arg1 geranial 487:494 geranial 487:494 geranial (39.4%) 487:502 The main volatile organic compounds were geranial (39.4%), neral (29.5%), and limonene (14.3%). 35684278 3 4 theme volatile 455:462 arg1 compounds 472:480 The main volatile organic compounds 446:480 The main volatile organic compounds 446:480 The main volatile organic compounds were geranial (39.4%), neral (29.5%), and limonene (14.3%). 35684278 6 5 theme Antimicrobial 881:893 arg1 activity 895:902 Antimicrobial activity 881:902 Antimicrobial activity of the LCEO vapor phase 881:926 Antimicrobial activity of the LCEO vapor phase showed strong inhibition of microorganisms on apples, pears, potatoes, and kohlrabies. 35684278 6 6 theme strong 935:940 arg1 inhibition 942:951 strong inhibition 935:951 strong inhibition of microorganisms 935:969 Antimicrobial activity of the LCEO vapor phase showed strong inhibition of microorganisms on apples, pears, potatoes, and kohlrabies. 35684278 3 7 theme organic 464:470 arg1 geranial 487:494 geranial 487:494 geranial (39.4%) 487:502 The main volatile organic compounds were geranial (39.4%), neral (29.5%), and limonene (14.3%). 35684278 3 7 theme organic 464:470 arg1 compounds 472:480 The main volatile organic compounds 446:480 The main volatile organic compounds 446:480 The main volatile organic compounds were geranial (39.4%), neral (29.5%), and limonene (14.3%). 35684278 0 8 theme Antimicrobial 85:97 arg1 Applications 99:110 Antioxidant and Antimicrobial Applications 69:110 Agricultural Products Safety: Antioxidant and Antimicrobial Applications 39:110 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 35684278 0 9 from Role 0:3 arg1 Products 52:59 Agricultural Products 39:59 Agricultural Products Safety: Antioxidant and Antimicrobial Applications 39:110 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 35684278 9 10 theme % 1303:1303 arg1 concentration 1284:1296 a concentration 1282:1296 a concentration of 25% 1282:1303 Anti-insect activity was also strong, with 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25%. 35684278 9 11 theme Anti-insect 1189:1199 arg1 activity 1201:1208 Anti-insect activity 1189:1208 Anti-insect activity 1189:1208 Anti-insect activity was also strong, with 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25%. 35684278 4 12 theme sample 623:628 arg1 mL 617:618 mL 617:618 mL of sample 617:628 Antioxidant activity was 30.9%, which was equal to 167.94 µg of Trolox per mL of sample. 35684278 7 13 theme bacteria 1059:1066 arg1 yeasts 1072:1077 yeasts 1072:1077 yeasts 1072:1077 Over 50% of gram-positive and gram-negative bacteria and yeasts were inhibited by a concentration of 500 µL/mL. 35684278 7 13 theme bacteria 1059:1066 arg1 bacteria 1059:1066 bacteria 1059:1066 bacteria 1059:1066 Over 50% of gram-positive and gram-negative bacteria and yeasts were inhibited by a concentration of 500 µL/mL. 35684278 7 13 theme bacteria 1059:1066 arg1 % 1022:1022 Over 50% 1015:1022 Over 50% of gram-positive and gram-negative bacteria and yeasts 1015:1077 Over 50% of gram-positive and gram-negative bacteria and yeasts were inhibited by a concentration of 500 µL/mL. 35684278 7 14 theme µL/mL 1120:1124 arg1 concentration 1099:1111 a concentration 1097:1111 a concentration of 500 µL/mL 1097:1124 Over 50% of gram-positive and gram-negative bacteria and yeasts were inhibited by a concentration of 500 µL/mL. 35684278 1 15 from cubeba 143:148 arg1 oil 127:129 The essential oil 113:129 The essential oil from Litsea cubeba (LCEO) 113:155 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 5 16 theme minimum 743:749 arg1 MIC 788:790 MIC 90 788:793 MIC 90 788:793 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 5 16 theme minimum 743:749 arg1 lowest 804:809 lowest 804:809 lowest 804:809 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 5 16 theme minimum 743:749 arg1 concentrations 762:775 minimum inhibitory concentrations 743:775 minimum inhibitory concentrations MIC 50 and MIC 90 743:793 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 5 16 theme minimum 743:749 arg1 MIC 777:779 MIC 50 777:782 MIC 50 777:782 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 10 17 used used 1359:1362 arg2 LCEO 1333:1336 LCEO 1333:1336 LCEO 1333:1336 These results suggest that LCEO could be potentially used as a food preservative. 35684278 10 17 used used 1359:1362 arg2 preservative 1374:1385 a food preservative 1367:1385 a food preservative 1367:1385 These results suggest that LCEO could be potentially used as a food preservative. 35684278 5 18 theme inhibitory 751:760 arg1 MIC 788:790 MIC 90 788:793 MIC 90 788:793 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 5 18 theme inhibitory 751:760 arg1 lowest 804:809 lowest 804:809 lowest 804:809 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 5 18 theme inhibitory 751:760 arg1 concentrations 762:775 minimum inhibitory concentrations 743:775 minimum inhibitory concentrations MIC 50 and MIC 90 743:793 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 5 18 theme inhibitory 751:760 arg1 MIC 777:779 MIC 50 777:782 MIC 50 777:782 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 2 19 theme related 403:409 arg1 activity 394:401 the biological activity 379:401 the biological activity related to food preservation 379:430 In this study the biological activity related to food preservation was observed. 35684278 9 20 theme 100 1232:1234 arg1 % 1235:1235 % 1235:1235 % 1235:1235 Anti-insect activity was also strong, with 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25%. 35684278 1 21 theme good 161:164 arg1 properties 206:215 good antioxidant, antimicrobial, anti-insect properties 161:215 good antioxidant, antimicrobial, anti-insect properties 161:215 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 7 22 theme gram-negative 1045:1057 arg1 bacteria 1059:1066 bacteria 1059:1066 bacteria 1059:1066 Over 50% of gram-positive and gram-negative bacteria and yeasts were inhibited by a concentration of 500 µL/mL. 35684278 9 23 with strong 1219:1224 arg1 lethality 1237:1245 100% lethality 1232:1245 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25% 1232:1303 Anti-insect activity was also strong, with 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25%. 35684278 4 24 theme Trolox 606:611 arg1 µg 600:601 167.94 µg 593:601 167.94 µg of Trolox 593:611 Antioxidant activity was 30.9%, which was equal to 167.94 µg of Trolox per mL of sample. 35684278 1 25 theme antioxidant 166:176 arg1 properties 206:215 good antioxidant, antimicrobial, anti-insect properties 161:215 good antioxidant, antimicrobial, anti-insect properties 161:215 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 0 26 theme cubeba 15:20 arg1 Oil 32:34 Litsea cubeba Essential Oil 8:34 Litsea cubeba Essential Oil 8:34 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 35684278 9 27 from concentration 1284:1296 arg1 apterus 1271:1277 apterus 1271:1277 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25% 1232:1303 Anti-insect activity was also strong, with 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25%. 35684278 5 28 theme strongest 665:673 arg1 inhibition 675:684 the strongest inhibition 661:684 the strongest inhibition against Serratia marcescens by disk diffusion method 661:737 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 5 29 theme disk 717:720 arg1 method 732:737 disk diffusion method 717:737 disk diffusion method 717:737 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 0 30 theme Litsea 8:13 arg1 Oil 32:34 Litsea cubeba Essential Oil 8:34 Litsea cubeba Essential Oil 8:34 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 35684278 0 31 dep Products 52:59 arg1 Applications 99:110 Antioxidant and Antimicrobial Applications 69:110 Agricultural Products Safety: Antioxidant and Antimicrobial Applications 39:110 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 35684278 0 31 dep Products 52:59 arg1 Safety 61:66 Safety 61:66 Agricultural Products Safety: Antioxidant and Antimicrobial Applications 39:110 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 35684278 5 32 theme diffusion 722:730 arg1 method 732:737 disk diffusion method 717:737 disk diffusion method 717:737 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 0 33 theme Oil 32:34 arg1 Role 0:3 Role 0:3 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 0:111 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 35684278 1 34 theme essential 117:125 arg1 oil 127:129 The essential oil 113:129 The essential oil from Litsea cubeba (LCEO) 113:155 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 6 35 theme phase 922:926 arg1 activity 895:902 Antimicrobial activity 881:902 Antimicrobial activity of the LCEO vapor phase 881:926 Antimicrobial activity of the LCEO vapor phase showed strong inhibition of microorganisms on apples, pears, potatoes, and kohlrabies. 35684278 5 36 dep concentrations 762:775 arg1 MIC 788:790 MIC 90 788:793 MIC 90 788:793 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 5 36 dep concentrations 762:775 arg1 concentrations 762:775 minimum inhibitory concentrations 743:775 minimum inhibitory concentrations MIC 50 and MIC 90 743:793 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 5 36 dep concentrations 762:775 arg1 MIC 777:779 MIC 50 777:782 MIC 50 777:782 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 4 37 theme Antioxidant 542:552 arg1 activity 554:561 Antioxidant activity 542:561 Antioxidant activity 542:561 Antioxidant activity was 30.9%, which was equal to 167.94 µg of Trolox per mL of sample. 35684278 0 38 theme Essential 22:30 arg1 Oil 32:34 Litsea cubeba Essential Oil 8:34 Litsea cubeba Essential Oil 8:34 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 35684278 9 39 theme % 1235:1235 arg1 lethality 1237:1245 100% lethality 1232:1245 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25% 1232:1303 Anti-insect activity was also strong, with 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25%. 35684278 1 40 theme shelf 353:357 arg1 life 359:362 shelf life 353:362 shelf life 353:362 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 1 41 dep antioxidant 166:176 arg1 antimicrobial 179:191 antimicrobial 179:191 antimicrobial 179:191 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 1 41 dep antioxidant 166:176 arg1 anti-insect 194:204 anti-insect 194:204 anti-insect 194:204 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 6 42 theme vapor 916:920 arg1 phase 922:926 the LCEO vapor phase 907:926 the LCEO vapor phase 907:926 Antimicrobial activity of the LCEO vapor phase showed strong inhibition of microorganisms on apples, pears, potatoes, and kohlrabies. 35684278 0 43 theme Agricultural 39:50 arg1 Products 52:59 Agricultural Products 39:59 Agricultural Products Safety: Antioxidant and Antimicrobial Applications 39:110 Role of Litsea cubeba Essential Oil in Agricultural Products Safety: Antioxidant and Antimicrobial Applications. 35684278 7 44 theme yeasts 1072:1077 arg1 yeasts 1072:1077 yeasts 1072:1077 yeasts 1072:1077 Over 50% of gram-positive and gram-negative bacteria and yeasts were inhibited by a concentration of 500 µL/mL. 35684278 7 44 theme yeasts 1072:1077 arg1 bacteria 1059:1066 bacteria 1059:1066 bacteria 1059:1066 Over 50% of gram-positive and gram-negative bacteria and yeasts were inhibited by a concentration of 500 µL/mL. 35684278 7 44 theme yeasts 1072:1077 arg1 % 1022:1022 Over 50% 1015:1022 Over 50% of gram-positive and gram-negative bacteria and yeasts 1015:1077 Over 50% of gram-positive and gram-negative bacteria and yeasts were inhibited by a concentration of 500 µL/mL. 35684278 4 45 theme 167.94 593:598 arg1 µg 600:601 167.94 µg 593:601 167.94 µg of Trolox 593:611 Antioxidant activity was 30.9%, which was equal to 167.94 µg of Trolox per mL of sample. 35684278 2 46 theme biological 383:392 arg1 activity 394:401 the biological activity 379:401 the biological activity related to food preservation 379:430 In this study the biological activity related to food preservation was observed. 35684278 1 47 theme food 280:283 arg1 resources 285:293 food resources 280:293 food resources 280:293 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 10 48 theme food 1369:1372 arg1 LCEO 1333:1336 LCEO 1333:1336 LCEO 1333:1336 These results suggest that LCEO could be potentially used as a food preservative. 35684278 10 48 theme food 1369:1372 arg1 preservative 1374:1385 a food preservative 1367:1385 a food preservative 1367:1385 These results suggest that LCEO could be potentially used as a food preservative. 35684278 1 49 dep has 157:159 arg1 gives 224:228 gives 224:228 gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life 224:362 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 1 50 contain has 157:159 arg1 oil 127:129 The essential oil 113:129 The essential oil from Litsea cubeba (LCEO) 113:155 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 1 50 contain has 157:159 arg2 properties 206:215 good antioxidant, antimicrobial, anti-insect properties 161:215 good antioxidant, antimicrobial, anti-insect properties 161:215 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 9 51 theme Pyrrhocoris& 1250:1264 arg1 lethality 1237:1245 100% lethality 1232:1245 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25% 1232:1303 Anti-insect activity was also strong, with 100% lethality of Pyrrhocoris&nbsp;apterus at a concentration of 25%. 35684278 8 52 theme microorganisms 1145:1158 arg1 dependent 1178:1186 dependent 1178:1186 dependent 1178:1186 The inhibition of microorganisms was concentration dependent. 35684278 8 52 theme microorganisms 1145:1158 arg1 inhibition 1131:1140 The inhibition 1127:1140 The inhibition of microorganisms 1127:1158 The inhibition of microorganisms was concentration dependent. 35684278 6 53 theme LCEO 911:914 arg1 phase 922:926 the LCEO vapor phase 907:926 the LCEO vapor phase 907:926 Antimicrobial activity of the LCEO vapor phase showed strong inhibition of microorganisms on apples, pears, potatoes, and kohlrabies. 35684278 5 54 dep µL/mL 860:864 arg1 3.52 855:858 3.52 855:858 3.52 855:858 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 5 54 dep µL/mL 860:864 arg1 1.46 846:849 1.46 846:849 1.46 846:849 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 1 55 theme Litsea 136:141 arg1 cubeba 143:148 Litsea cubeba 136:148 Litsea cubeba (LCEO) 136:155 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 1 55 theme Litsea 136:141 arg1 LCEO 151:154 LCEO 151:154 LCEO 151:154 The essential oil from Litsea cubeba (LCEO) has good antioxidant, antimicrobial, anti-insect properties, which gives it the potential for use as a natural additive to food resources and food products in order to prevent spoilage and extend shelf life. 35684278 6 56 theme microorganisms 956:969 arg1 inhibition 942:951 strong inhibition 935:951 strong inhibition of microorganisms 935:969 Antimicrobial activity of the LCEO vapor phase showed strong inhibition of microorganisms on apples, pears, potatoes, and kohlrabies. 35684278 2 57 theme food 414:417 arg1 preservation 419:430 food preservation 414:430 food preservation 414:430 In this study the biological activity related to food preservation was observed. 35684278 7 58 theme gram-positive 1027:1039 arg1 bacteria 1059:1066 bacteria 1059:1066 bacteria 1059:1066 Over 50% of gram-positive and gram-negative bacteria and yeasts were inhibited by a concentration of 500 µL/mL. 35684278 2 59 located observed 436:443 arg2 activity 394:401 the biological activity 379:401 the biological activity related to food preservation 379:430 In this study the biological activity related to food preservation was observed. 35684278 2 59 located observed 436:443 arg1 study 373:377 this study 368:377 this study 368:377 In this study the biological activity related to food preservation was observed. 35684278 5 60 dep values 839:844 arg1 µL/mL 860:864 µL/mL 860:864 µL/mL 860:864 Antimicrobial activity showed the strongest inhibition against Serratia marcescens by disk diffusion method and minimum inhibitory concentrations MIC 50 and MIC 90 were the lowest for Micrococcus luteus with values 1.46 and 3.52 µL/mL, respectively. 35684278 3 61 theme main 450:453 arg1 geranial 487:494 geranial 487:494 geranial (39.4%) 487:502 The main volatile organic compounds were geranial (39.4%), neral (29.5%), and limonene (14.3%). 35684278 3 61 theme main 450:453 arg1 compounds 472:480 The main volatile organic compounds 446:480 The main volatile organic compounds 446:480 The main volatile organic compounds were geranial (39.4%), neral (29.5%), and limonene (14.3%). 35458264 0 0 theme Acid-Rich 64:72 arg1 Polysaccharides 74:88 Uronic Acid-Rich Polysaccharides 57:88 Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis 57:121 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 0 1 from Obesity 16:22 arg1 Mice 27:30 Mice 27:30 Mice 27:30 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 1 2 theme changes 249:255 arg1 Westernization 207:220 the Westernization 203:220 the Westernization of societies and lifestyle changes 203:255 Obesity is rapidly becoming an emerging disease in developing countries due to the Westernization of societies and lifestyle changes. 35458264 0 3 theme Uronic 57:62 arg1 Polysaccharides 74:88 Uronic Acid-Rich Polysaccharides 57:88 Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis 57:121 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 1 4 theme emerging 155:162 arg1 disease 164:170 an emerging disease 152:170 an emerging disease in developing countries due to the Westernization of societies and lifestyle changes 152:255 Obesity is rapidly becoming an emerging disease in developing countries due to the Westernization of societies and lifestyle changes. 35458264 6 5 theme obesity 920:926 arg1 features 908:915 features 908:915 features of obesity 908:926 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 8 6 theme diet-induced 1267:1278 arg1 obesity 1280:1286 the diet-induced obesity 1263:1286 the diet-induced obesity in the mice 1263:1298 In conclusion, the TFPS treatment ameliorated the diet-induced obesity in the mice, presumably reducing fat absorption in the intestine by interfering with viscous TFPS. 35458264 0 7 from Amelioration 0:11 arg1 Mice 27:30 Mice 27:30 Mice 27:30 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 0 8 dep Tremella 103:110 arg1 fuciformis 112:121 Tremella fuciformis 103:121 Tremella fuciformis 103:121 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 6 9 theme fecal 1041:1045 arg1 content 1053:1059 fecal lipid content 1041:1059 fecal lipid content 1041:1059 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 6 10 with HFD 1088:1090 arg1 water 1097:1101 water 1097:1101 water 1097:1101 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 2 11 theme ameliorative 283:294 arg1 effect 296:301 the ameliorative effect 279:301 the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice 279:431 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 4 12 theme molecular 566:574 arg1 weight 576:581 average molecular weight 558:581 average molecular weight 558:581 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 7 13 theme micelles 1162:1169 arg1 inhibition 1136:1145 the inhibition 1132:1145 the inhibition of cholesterol micelles 1132:1169 In addition, TFPS exhibited the inhibition of cholesterol micelles in vitro in a concentration-dependent manner. 35458264 0 14 with Diet 47:50 arg1 Polysaccharides 74:88 Uronic Acid-Rich Polysaccharides 57:88 Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis 57:121 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 5 15 theme weight 847:852 arg1 g/kg 834:837 1 and 2 g/kg 826:837 1 and 2 g/kg of body weight for 8 weeks 826:864 In an in vivo study, HFD-induced obese C57BL/6 mice were orally given a TFPS treatment at 1 and 2 g/kg of body weight for 8 weeks. 35458264 6 16 theme fat 983:985 arg1 mice 935:938 the mice 931:938 the mice 931:938 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 6 16 theme fat 983:985 arg1 percentage 987:996 body fat percentage 978:996 body fat percentage 978:996 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 6 17 theme weight 948:953 arg1 mice 935:938 the mice 931:938 the mice 931:938 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 6 17 theme weight 948:953 arg1 gain 955:958 weight gain 948:958 weight gain 948:958 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 4 18 theme average 558:564 arg1 weight 576:581 average molecular weight 558:581 average molecular weight 558:581 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 4 19 from ratio 698:702 arg1 fucose 673:678 fucose 673:678 fucose 673:678 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 4 19 from ratio 698:702 arg1 composition 619:629 the monosaccharide composition 600:629 the monosaccharide composition 600:629 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 4 19 from ratio 698:702 arg1 fructose 655:662 fructose 655:662 fructose 655:662 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 4 19 from ratio 698:702 arg1 mannose 685:691 mannose 685:691 mannose 685:691 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 4 19 from ratio 698:702 arg1 xylose 665:670 xylose 665:670 xylose 665:670 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 4 19 from ratio 698:702 arg1 kDa 591:593 679 kDa 587:593 679 kDa 587:593 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 4 19 from ratio 698:702 arg1 galactose 635:643 galactose 635:643 galactose 635:643 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 4 19 from ratio 698:702 arg1 glucose 646:652 glucose 646:652 glucose 646:652 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 8 20 theme TFPS 1236:1239 arg1 treatment 1241:1249 the TFPS treatment 1232:1249 the TFPS treatment 1232:1249 In conclusion, the TFPS treatment ameliorated the diet-induced obesity in the mice, presumably reducing fat absorption in the intestine by interfering with viscous TFPS. 35458264 5 21 theme TFPS 808:811 arg1 treatment 813:821 a TFPS treatment 806:821 a TFPS treatment 806:821 In an in vivo study, HFD-induced obese C57BL/6 mice were orally given a TFPS treatment at 1 and 2 g/kg of body weight for 8 weeks. 35458264 0 22 from Mice 27:30 arg1 Amelioration 0:11 Amelioration 0:11 Amelioration of Obesity in Mice 0:30 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 7 23 theme concentration-dependent 1185:1207 arg1 manner 1209:1214 a concentration-dependent manner 1183:1214 a concentration-dependent manner 1183:1214 In addition, TFPS exhibited the inhibition of cholesterol micelles in vitro in a concentration-dependent manner. 35458264 7 24 theme cholesterol 1150:1160 arg1 micelles 1162:1169 cholesterol micelles 1150:1169 cholesterol micelles 1150:1169 In addition, TFPS exhibited the inhibition of cholesterol micelles in vitro in a concentration-dependent manner. 35458264 1 25 theme developing 175:184 arg1 countries 186:194 developing countries 175:194 developing countries 175:194 Obesity is rapidly becoming an emerging disease in developing countries due to the Westernization of societies and lifestyle changes. 35458264 5 26 theme HFD-induced 757:767 arg1 mice 783:786 HFD-induced obese C57BL/6 mice 757:786 HFD-induced obese C57BL/6 mice 757:786 In an in vivo study, HFD-induced obese C57BL/6 mice were orally given a TFPS treatment at 1 and 2 g/kg of body weight for 8 weeks. 35458264 5 27 dep in 742:743 arg1 vivo 745:748 vivo 745:748 vivo 745:748 In an in vivo study, HFD-induced obese C57BL/6 mice were orally given a TFPS treatment at 1 and 2 g/kg of body weight for 8 weeks. 35458264 2 28 theme heteropolysaccharides 313:333 arg1 effect 296:301 the ameliorative effect 279:301 the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice 279:431 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 4 29 theme 1.0:6.5:10.0:18.5:30.5:67.5 707:733 arg1 ratio 698:702 a ratio 696:702 a ratio of 1.0:6.5:10.0:18.5:30.5:67.5 696:733 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 5 30 theme obese 769:773 arg1 mice 783:786 HFD-induced obese C57BL/6 mice 757:786 HFD-induced obese C57BL/6 mice 757:786 In an in vivo study, HFD-induced obese C57BL/6 mice were orally given a TFPS treatment at 1 and 2 g/kg of body weight for 8 weeks. 35458264 2 31 attach derived 335:341 arg1 fuciformis 357:366 Tremella fuciformis 348:366 Tremella fuciformis (TFPS) 348:373 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 2 31 attach derived 335:341 arg2 heteropolysaccharides 313:333 acidic heteropolysaccharides 306:333 acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) 306:373 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 2 31 attach derived 335:341 arg1 TFPS 369:372 TFPS 369:372 TFPS 369:372 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 2 32 theme acidic 306:311 arg1 heteropolysaccharides 313:333 acidic heteropolysaccharides 306:333 acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) 306:373 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 6 33 theme feed 961:964 arg1 mice 935:938 the mice 931:938 the mice 931:938 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 6 33 theme feed 961:964 arg1 efficiency 966:975 feed efficiency 961:975 feed efficiency 961:975 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 2 34 theme -induced 408:415 arg1 obesity 417:423 high-fat diet (HFD; 34.9% fat)-induced obesity 378:423 high-fat diet (HFD; 34.9% fat)-induced obesity in mice 378:431 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 3 35 theme high 482:485 arg1 viscosity 487:495 high viscosity 482:495 high viscosity 482:495 The TFPS exhibited high uronic acid content and high viscosity in water. 35458264 6 36 theme serum 1003:1007 arg1 level 1021:1025 serum cholesterol level 1003:1025 serum cholesterol level 1003:1025 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 6 36 theme serum 1003:1007 arg1 mice 935:938 the mice 931:938 the mice 931:938 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 4 37 theme TFPS 541:544 arg1 characteristics 522:536 The structural characteristics 507:536 The structural characteristics of TFPS 507:544 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 8 38 theme viscous 1373:1379 arg1 TFPS 1381:1384 viscous TFPS 1373:1384 viscous TFPS 1373:1384 In conclusion, the TFPS treatment ameliorated the diet-induced obesity in the mice, presumably reducing fat absorption in the intestine by interfering with viscous TFPS. 35458264 6 39 theme TFPS 871:874 arg1 treatment 876:884 The TFPS treatment 867:884 The TFPS treatment 867:884 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 8 40 from absorption 1325:1334 arg1 intestine 1343:1351 the intestine 1339:1351 the intestine 1339:1351 In conclusion, the TFPS treatment ameliorated the diet-induced obesity in the mice, presumably reducing fat absorption in the intestine by interfering with viscous TFPS. 35458264 2 41 theme % 402:402 arg1 fat 404:406 34.9% fat 398:406 HFD; 34.9% fat 393:406 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 5 42 theme in 742:743 arg1 study 750:754 an in vivo study 739:754 an in vivo study 739:754 In an in vivo study, HFD-induced obese C57BL/6 mice were orally given a TFPS treatment at 1 and 2 g/kg of body weight for 8 weeks. 35458264 2 43 theme 34.9 398:401 arg1 % 402:402 % 402:402 % 402:402 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 0 44 theme High-Fat 38:45 arg1 Diet 47:50 a High-Fat Diet 36:50 a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis 36:121 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 5 45 theme C57BL/6 775:781 arg1 mice 783:786 HFD-induced obese C57BL/6 mice 757:786 HFD-induced obese C57BL/6 mice 757:786 In an in vivo study, HFD-induced obese C57BL/6 mice were orally given a TFPS treatment at 1 and 2 g/kg of body weight for 8 weeks. 35458264 3 46 theme acid 465:468 arg1 content 470:476 high uronic acid content 453:476 high uronic acid content 453:476 The TFPS exhibited high uronic acid content and high viscosity in water. 35458264 4 47 theme structural 511:520 arg1 characteristics 522:536 The structural characteristics 507:536 The structural characteristics of TFPS 507:544 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 3 48 theme high 453:456 arg1 content 470:476 high uronic acid content 453:476 high uronic acid content 453:476 The TFPS exhibited high uronic acid content and high viscosity in water. 35458264 8 49 theme fat 1321:1323 arg1 absorption 1325:1334 fat absorption 1321:1334 fat absorption in the intestine 1321:1351 In conclusion, the TFPS treatment ameliorated the diet-induced obesity in the mice, presumably reducing fat absorption in the intestine by interfering with viscous TFPS. 35458264 5 50 theme body 842:845 arg1 weight 847:852 body weight 842:852 body weight 842:852 In an in vivo study, HFD-induced obese C57BL/6 mice were orally given a TFPS treatment at 1 and 2 g/kg of body weight for 8 weeks. 35458264 2 51 dep HFD 393:395 arg1 fat 404:406 34.9% fat 398:406 HFD; 34.9% fat 393:406 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 2 52 theme Tremella 348:355 arg1 fuciformis 357:366 Tremella fuciformis 348:366 Tremella fuciformis (TFPS) 348:373 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 2 52 theme Tremella 348:355 arg1 TFPS 369:372 TFPS 369:372 TFPS 369:372 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 6 53 theme lipid 1047:1051 arg1 content 1053:1059 fecal lipid content 1041:1059 fecal lipid content 1041:1059 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 6 54 theme cholesterol 1009:1019 arg1 level 1021:1025 serum cholesterol level 1003:1025 serum cholesterol level 1003:1025 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 6 54 theme cholesterol 1009:1019 arg1 mice 935:938 the mice 931:938 the mice 931:938 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 2 55 dep diet 387:390 arg1 HFD 393:395 HFD 393:395 HFD; 34.9% fat 393:406 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 3 56 theme uronic 458:463 arg1 content 470:476 high uronic acid content 453:476 high uronic acid content 453:476 The TFPS exhibited high uronic acid content and high viscosity in water. 35458264 2 57 from effect 296:301 arg1 obesity 417:423 high-fat diet (HFD; 34.9% fat)-induced obesity 378:423 high-fat diet (HFD; 34.9% fat)-induced obesity in mice 378:431 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 1 58 theme societies 225:233 arg1 Westernization 207:220 the Westernization 203:220 the Westernization of societies and lifestyle changes 203:255 Obesity is rapidly becoming an emerging disease in developing countries due to the Westernization of societies and lifestyle changes. 35458264 4 59 theme monosaccharide 604:617 arg1 galactose 635:643 galactose 635:643 galactose 635:643 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 4 59 theme monosaccharide 604:617 arg1 composition 619:629 the monosaccharide composition 600:629 the monosaccharide composition 600:629 The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. 35458264 0 60 attach Derived 90:96 arg2 Polysaccharides 74:88 Uronic Acid-Rich Polysaccharides 57:88 Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis 57:121 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 0 60 attach Derived 90:96 arg1 Tremella 103:110 Tremella 103:110 Tremella 103:110 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 2 61 theme high-fat 378:385 arg1 diet 387:390 high-fat diet 378:390 high-fat diet (HFD; 34.9% fat) 378:407 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 6 62 theme body 978:981 arg1 mice 935:938 the mice 931:938 the mice 931:938 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 6 62 theme body 978:981 arg1 percentage 987:996 body fat percentage 978:996 body fat percentage 978:996 The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. 35458264 2 63 from obesity 417:423 arg1 mice 428:431 mice 428:431 mice 428:431 This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. 35458264 0 64 theme Obesity 16:22 arg1 Amelioration 0:11 Amelioration 0:11 Amelioration of Obesity in Mice 0:30 Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis. 35458264 1 65 from disease 164:170 arg1 countries 186:194 developing countries 175:194 developing countries 175:194 Obesity is rapidly becoming an emerging disease in developing countries due to the Westernization of societies and lifestyle changes. 35458264 8 66 from obesity 1280:1286 arg1 mice 1295:1298 the mice 1291:1298 the mice 1291:1298 In conclusion, the TFPS treatment ameliorated the diet-induced obesity in the mice, presumably reducing fat absorption in the intestine by interfering with viscous TFPS. 35458264 1 67 theme lifestyle 239:247 arg1 changes 249:255 lifestyle changes 239:255 lifestyle changes 239:255 Obesity is rapidly becoming an emerging disease in developing countries due to the Westernization of societies and lifestyle changes. 37063983 4 0 theme area 958:961 arg1 integration 963:973 peak area integration 953:973 peak area integration 953:973 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 2 1 used used 596:599 arg2 SEM 587:589 SEM 587:589 SEM 587:589 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 1 used used 596:599 arg2 modelling 576:584 structural equation modelling 556:584 structural equation modelling (SEM) 556:590 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 6 2 theme trees 1348:1352 arg1 succession 1323:1332 multi-generation succession 1306:1332 multi-generation succession of eucalyptus trees 1306:1352 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 6 3 theme functional 1484:1493 arg1 groups 1495:1500 aromatic and phenolic alcohol functional groups 1454:1500 aromatic and phenolic alcohol functional groups 1454:1500 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 2 4 from fertility 631:639 arg1 biomass 688:694 stand biomass 682:694 stand biomass 682:694 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 5 theme equation 567:574 arg1 SEM 587:589 SEM 587:589 SEM 587:589 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 5 theme equation 567:574 arg1 modelling 576:584 structural equation modelling 556:584 structural equation modelling (SEM) 556:590 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 6 6 theme composition 1412:1422 arg1 structure 1369:1377 the structure 1365:1377 the structure of soil organic functional group composition 1365:1422 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 4 7 theme aromatics 999:1007 arg1 higher 1049:1054 higher 1049:1054 higher 1049:1054 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 4 7 theme aromatics 999:1007 arg1 content 980:986 the content 976:986 the content of esters, aromatics and phenolic alcohols 976:1029 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 0 8 theme enzyme 103:108 arg1 activity 110:117 enzyme activity 103:117 enzyme activity 103:117 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 2 9 theme different 350:358 arg1 ages 366:369 different stand ages 350:369 different stand ages (5, 11, 17 and 21 years old) 350:398 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 6 10 theme functional 1395:1404 arg1 composition 1412:1422 soil organic functional group composition 1382:1422 soil organic functional group composition 1382:1422 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 4 11 theme phenolic 1013:1020 arg1 alcohols 1022:1029 phenolic alcohols 1013:1029 phenolic alcohols 1013:1029 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 2 12 from fraction 670:677 arg1 biomass 688:694 stand biomass 682:694 stand biomass 682:694 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 13 theme fertility 631:639 arg1 influences 612:621 influences 612:621 influences of soil fertility, enzyme activity and organic fraction on stand biomass 612:694 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 1 14 theme succession 202:211 arg1 effects 172:178 the effects 168:178 the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties 168:288 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 0 15 from effects 51:57 arg1 biomass 133:139 eucalyptus biomass 122:139 eucalyptus biomass 122:139 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 3 16 theme FTIR 697:700 arg1 analysis 702:709 FTIR analysis 697:709 FTIR analysis 697:709 FTIR analysis showed that 11 infrared absorption peaks existed in the soils of this study area, attributed to silicates, aromatics, carbonate ions, sugars, esters, polysaccharides, aliphatic hydrocarbons and phenolic alcohols. 37063983 1 17 from effects 172:178 arg1 properties 279:288 biological properties 268:288 biological properties 268:288 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 1 17 from effects 172:178 arg1 fertility 235:243 soil fertility 230:243 soil fertility 230:243 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 1 17 from effects 172:178 arg1 structure 254:262 organic structure 246:262 organic structure 246:262 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 3 18 theme study 781:785 arg1 area 787:790 this study area 776:790 this study area 776:790 FTIR analysis showed that 11 infrared absorption peaks existed in the soils of this study area, attributed to silicates, aromatics, carbonate ions, sugars, esters, polysaccharides, aliphatic hydrocarbons and phenolic alcohols. 37063983 2 19 theme soil 626:629 arg1 fertility 631:639 soil fertility 626:639 soil fertility 626:639 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 3 20 theme absorption 735:744 arg1 peaks 746:750 11 infrared absorption peaks 723:750 11 infrared absorption peaks 723:750 FTIR analysis showed that 11 infrared absorption peaks existed in the soils of this study area, attributed to silicates, aromatics, carbonate ions, sugars, esters, polysaccharides, aliphatic hydrocarbons and phenolic alcohols. 37063983 6 21 theme phenolic 1467:1474 arg1 groups 1495:1500 aromatic and phenolic alcohol functional groups 1454:1500 aromatic and phenolic alcohol functional groups 1454:1500 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 2 22 theme organic 438:444 arg1 structure 455:463 soil organic fraction structure and content characteristics 433:491 structure 455:463 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 6 23 theme eucalyptus 1337:1346 arg1 trees 1348:1352 eucalyptus trees 1337:1352 eucalyptus trees 1337:1352 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 4 24 theme 17- 1059:1061 arg1 soils 1085:1089 17- and 21-year-old stand soils 1059:1089 17- and 21-year-old stand soils 1059:1089 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 7 25 dep inhibit 1529:1535 arg1 affect 1598:1603 affect 1598:1603 affect biomass by inhibiting enzyme activity 1598:1641 Such changes can directly inhibit the increase in eucalyptus biomass and indirectly negatively affect biomass by inhibiting enzyme activity. 37063983 6 26 theme aromatic 1454:1461 arg1 groups 1495:1500 aromatic and phenolic alcohol functional groups 1454:1500 aromatic and phenolic alcohol functional groups 1454:1500 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 2 27 theme activity 649:656 arg1 influences 612:621 influences 612:621 influences of soil fertility, enzyme activity and organic fraction on stand biomass 612:694 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 0 28 theme soil 62:65 arg1 environment 76:86 soil chemical environment 62:86 soil chemical environment 62:86 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 2 29 theme content 469:475 arg1 characteristics 477:491 soil organic fraction structure and content characteristics 433:491 characteristics 477:491 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 0 30 theme environment 76:86 arg1 effects 51:57 the effects 47:57 the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass 47:139 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 0 31 theme fertility 89:97 arg1 effects 51:57 the effects 47:57 the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass 47:139 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 0 32 used used 30:33 arg2 model 20:24 Structural equation model 0:24 Structural equation model 0:24 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 0 33 theme Structural 0:9 arg1 model 20:24 Structural equation model 0:24 Structural equation model 0:24 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 4 34 theme peak 953:956 arg1 integration 963:973 peak area integration 953:973 peak area integration 953:973 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 2 35 theme organic 662:668 arg1 fraction 670:677 organic fraction 662:677 organic fraction 662:677 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 7 36 theme eucalyptus 1553:1562 arg1 biomass 1564:1570 eucalyptus biomass 1553:1570 eucalyptus biomass 1553:1570 Such changes can directly inhibit the increase in eucalyptus biomass and indirectly negatively affect biomass by inhibiting enzyme activity. 37063983 2 37 theme south 421:425 arg1 Asia 427:430 south Asia 421:430 south Asia 421:430 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 5 38 theme enzyme 1202:1207 arg1 activity 1209:1216 enzyme activity 1202:1216 enzyme activity 1202:1216 The results of SEM showed that organic components were negatively related (p < 0.01) to enzyme activity and biomass, with standardized coefficients of 0.53 and 0.49, respectively. 37063983 2 39 theme eucalyptus 324:333 arg1 plantations 335:345 eucalyptus plantations 324:345 eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) 324:398 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 5 40 theme standardized 1236:1247 arg1 coefficients 1249:1260 standardized coefficients 1236:1260 standardized coefficients of 0.53 and 0.49, respectively 1236:1291 The results of SEM showed that organic components were negatively related (p < 0.01) to enzyme activity and biomass, with standardized coefficients of 0.53 and 0.49, respectively. 37063983 3 41 theme aliphatic 878:886 arg1 hydrocarbons 888:899 aliphatic hydrocarbons 878:899 aliphatic hydrocarbons 878:899 FTIR analysis showed that 11 infrared absorption peaks existed in the soils of this study area, attributed to silicates, aromatics, carbonate ions, sugars, esters, polysaccharides, aliphatic hydrocarbons and phenolic alcohols. 37063983 4 42 theme integration 963:973 arg1 results 942:948 the results 938:948 the results of peak area integration 938:973 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 2 43 theme stand 360:364 arg1 ages 366:369 different stand ages 350:369 different stand ages (5, 11, 17 and 21 years old) 350:398 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 44 dep infrared 535:542 arg1 FTIR 545:548 FTIR 545:548 FTIR 545:548 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 4 45 theme 21-year-old 1067:1077 arg1 soils 1085:1089 17- and 21-year-old stand soils 1059:1089 17- and 21-year-old stand soils 1059:1089 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 1 46 theme organic 246:252 arg1 fertility 235:243 soil fertility 230:243 soil fertility 230:243 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 1 46 theme organic 246:252 arg1 structure 254:262 organic structure 246:262 organic structure 246:262 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 5 47 dep related 1180:1186 arg1 < 1191:1191 p < 0.01 1189:1196 p < 0.01 1189:1196 The results of SEM showed that organic components were negatively related (p < 0.01) to enzyme activity and biomass, with standardized coefficients of 0.53 and 0.49, respectively. 37063983 2 48 theme stand 682:686 arg1 biomass 688:694 stand biomass 682:694 stand biomass 682:694 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 49 theme structural 556:565 arg1 SEM 587:589 SEM 587:589 SEM 587:589 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 49 theme structural 556:565 arg1 modelling 576:584 structural equation modelling 556:584 structural equation modelling (SEM) 556:590 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 0 50 theme activity 110:117 arg1 effects 51:57 the effects 47:57 the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass 47:139 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 6 51 theme group 1406:1410 arg1 composition 1412:1422 soil organic functional group composition 1382:1422 soil organic functional group composition 1382:1422 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 4 52 theme alcohols 1022:1029 arg1 higher 1049:1054 higher 1049:1054 higher 1049:1054 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 4 52 theme alcohols 1022:1029 arg1 content 980:986 the content 976:986 the content of esters, aromatics and phenolic alcohols 976:1029 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 2 53 from activity 649:656 arg1 biomass 688:694 stand biomass 682:694 stand biomass 682:694 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 0 54 theme eucalyptus 122:131 arg1 biomass 133:139 eucalyptus biomass 122:139 eucalyptus biomass 122:139 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 6 55 theme organic 1387:1393 arg1 composition 1412:1422 soil organic functional group composition 1382:1422 soil organic functional group composition 1382:1422 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 1 56 theme multi-generational 183:200 arg1 succession 202:211 multi-generational succession 183:211 multi-generational succession of eucalyptus 183:225 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 2 57 theme enzyme 642:647 arg1 activity 649:656 enzyme activity 642:656 enzyme activity 642:656 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 6 58 theme groups 1495:1500 arg1 enrichment 1440:1449 the enrichment 1436:1449 the enrichment of aromatic and phenolic alcohol functional groups 1436:1500 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 7 59 theme Such 1503:1506 arg1 changes 1508:1514 Such changes 1503:1514 Such changes 1503:1514 Such changes can directly inhibit the increase in eucalyptus biomass and indirectly negatively affect biomass by inhibiting enzyme activity. 37063983 4 60 theme control 1099:1105 arg1 soils 1107:1111 control soils 1099:1111 control soils 1099:1111 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 6 61 theme alcohol 1476:1482 arg1 groups 1495:1500 aromatic and phenolic alcohol functional groups 1454:1500 aromatic and phenolic alcohol functional groups 1454:1500 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 3 62 theme area 787:790 arg1 soils 767:771 the soils 763:771 the soils 763:771 FTIR analysis showed that 11 infrared absorption peaks existed in the soils of this study area, attributed to silicates, aromatics, carbonate ions, sugars, esters, polysaccharides, aliphatic hydrocarbons and phenolic alcohols. 37063983 2 63 theme fraction 670:677 arg1 influences 612:621 influences 612:621 influences of soil fertility, enzyme activity and organic fraction on stand biomass 612:694 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 5 64 theme p 1189:1189 arg1 < 1191:1191 p < 0.01 1189:1196 p < 0.01 1189:1196 The results of SEM showed that organic components were negatively related (p < 0.01) to enzyme activity and biomass, with standardized coefficients of 0.53 and 0.49, respectively. 37063983 7 65 theme enzyme 1627:1632 arg1 activity 1634:1641 enzyme activity 1627:1641 enzyme activity 1627:1641 Such changes can directly inhibit the increase in eucalyptus biomass and indirectly negatively affect biomass by inhibiting enzyme activity. 37063983 2 66 theme soil 433:436 arg1 structure 455:463 soil organic fraction structure and content characteristics 433:491 structure 455:463 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 4 67 theme stand 1079:1083 arg1 soils 1085:1089 17- and 21-year-old stand soils 1059:1089 17- and 21-year-old stand soils 1059:1089 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 5 68 theme organic 1145:1151 arg1 components 1153:1162 organic components 1145:1162 organic components 1145:1162 The results of SEM showed that organic components were negatively related (p < 0.01) to enzyme activity and biomass, with standardized coefficients of 0.53 and 0.49, respectively. 37063983 3 69 theme infrared 726:733 arg1 peaks 746:750 11 infrared absorption peaks 723:750 11 infrared absorption peaks 723:750 FTIR analysis showed that 11 infrared absorption peaks existed in the soils of this study area, attributed to silicates, aromatics, carbonate ions, sugars, esters, polysaccharides, aliphatic hydrocarbons and phenolic alcohols. 37063983 0 70 theme chemical 67:74 arg1 environment 76:86 soil chemical environment 62:86 soil chemical environment 62:86 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 2 71 from influences 612:621 arg1 biomass 688:694 stand biomass 682:694 stand biomass 682:694 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 72 theme Soil 291:294 arg1 samples 296:302 Soil samples 291:302 Soil samples 291:302 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 73 from area 413:416 arg1 Asia 427:430 south Asia 421:430 south Asia 421:430 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 3 74 theme carbonate 829:837 arg1 ions 839:842 carbonate ions 829:842 carbonate ions 829:842 FTIR analysis showed that 11 infrared absorption peaks existed in the soils of this study area, attributed to silicates, aromatics, carbonate ions, sugars, esters, polysaccharides, aliphatic hydrocarbons and phenolic alcohols. 37063983 2 75 theme fraction 446:453 arg1 structure 455:463 soil organic fraction structure and content characteristics 433:491 structure 455:463 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 76 dep ages 366:369 arg1 old 395:397 old 395:397 old 395:397 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 0 77 theme equation 11:18 arg1 model 20:24 Structural equation model 0:24 Structural equation model 0:24 Structural equation model was used to evaluate the effects of soil chemical environment, fertility and enzyme activity on eucalyptus biomass. 37063983 7 78 from increase 1541:1548 arg1 biomass 1564:1570 eucalyptus biomass 1553:1570 eucalyptus biomass 1553:1570 Such changes can directly inhibit the increase in eucalyptus biomass and indirectly negatively affect biomass by inhibiting enzyme activity. 37063983 6 79 theme multi-generation 1306:1321 arg1 succession 1323:1332 multi-generation succession 1306:1332 multi-generation succession of eucalyptus trees 1306:1352 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 1 80 theme biological 268:277 arg1 properties 279:288 biological properties 268:288 biological properties 268:288 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 1 80 theme biological 268:277 arg1 fertility 235:243 soil fertility 230:243 soil fertility 230:243 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 5 81 theme 0.53 1265:1268 arg1 coefficients 1249:1260 standardized coefficients 1236:1260 standardized coefficients of 0.53 and 0.49, respectively 1236:1291 The results of SEM showed that organic components were negatively related (p < 0.01) to enzyme activity and biomass, with standardized coefficients of 0.53 and 0.49, respectively. 37063983 1 82 theme eucalyptus 216:225 arg1 succession 202:211 multi-generational succession 183:211 multi-generational succession of eucalyptus 183:225 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 5 83 with related 1180:1186 arg1 coefficients 1249:1260 standardized coefficients 1236:1260 standardized coefficients of 0.53 and 0.49, respectively 1236:1291 The results of SEM showed that organic components were negatively related (p < 0.01) to enzyme activity and biomass, with standardized coefficients of 0.53 and 0.49, respectively. 37063983 2 84 theme typical 405:411 arg1 area 413:416 a typical area 403:416 a typical area in south Asia 403:430 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 2 85 from biomass 688:694 arg1 influences 612:621 influences 612:621 influences of soil fertility, enzyme activity and organic fraction on stand biomass 612:694 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 5 86 theme 0.49 1274:1277 arg1 coefficients 1249:1260 standardized coefficients 1236:1260 standardized coefficients of 0.53 and 0.49, respectively 1236:1291 The results of SEM showed that organic components were negatively related (p < 0.01) to enzyme activity and biomass, with standardized coefficients of 0.53 and 0.49, respectively. 37063983 6 87 theme soil 1382:1385 arg1 composition 1412:1422 soil organic functional group composition 1382:1422 soil organic functional group composition 1382:1422 In summary, multi-generation succession of eucalyptus trees can change the structure of soil organic functional group composition and promote the enrichment of aromatic and phenolic alcohol functional groups. 37063983 5 88 theme SEM 1129:1131 arg1 results 1118:1124 The results 1114:1124 The results of SEM 1114:1131 The results of SEM showed that organic components were negatively related (p < 0.01) to enzyme activity and biomass, with standardized coefficients of 0.53 and 0.49, respectively. 37063983 3 89 theme phenolic 905:912 arg1 alcohols 914:921 phenolic alcohols 905:921 phenolic alcohols 905:921 FTIR analysis showed that 11 infrared absorption peaks existed in the soils of this study area, attributed to silicates, aromatics, carbonate ions, sugars, esters, polysaccharides, aliphatic hydrocarbons and phenolic alcohols. 37063983 4 90 theme esters 991:996 arg1 higher 1049:1054 higher 1049:1054 higher 1049:1054 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 4 90 theme esters 991:996 arg1 content 980:986 the content 976:986 the content of esters, aromatics and phenolic alcohols 976:1029 Combined with the results of peak area integration, the content of esters, aromatics and phenolic alcohols was significantly higher in 17- and 21-year-old stand soils than in control soils. 37063983 2 91 theme ages 366:369 arg1 plantations 335:345 eucalyptus plantations 324:345 eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) 324:398 Soil samples were collected from eucalyptus plantations of different stand ages (5, 11, 17 and 21 years old) in a typical area in south Asia, soil organic fraction structure and content characteristics were investigated using Fourier transform infrared (FTIR), and structural equation modelling (SEM) was used to explore influences of soil fertility, enzyme activity and organic fraction on stand biomass. 37063983 1 92 theme soil 230:233 arg1 properties 279:288 biological properties 268:288 biological properties 268:288 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 1 92 theme soil 230:233 arg1 fertility 235:243 soil fertility 230:243 soil fertility 230:243 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 37063983 1 92 theme soil 230:233 arg1 structure 254:262 organic structure 246:262 organic structure 246:262 This paper aims to reveal the effects of multi-generational succession of eucalyptus on soil fertility, organic structure and biological properties. 36803175 6 0 from compounds 890:898 arg1 plants 913:918 medicinal plants 903:918 medicinal plants 903:918 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 6 1 theme chemical 881:888 arg1 compounds 890:898 chemical compounds 881:898 chemical compounds in medicinal plants 881:918 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 3 2 from enrichment 393:402 arg1 polysaccharides 461:475 polysaccharides 461:475 polysaccharides 461:475 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 3 2 from enrichment 393:402 arg1 flavonoids 446:455 flavonoids 446:455 flavonoids 446:455 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 3 2 from enrichment 393:402 arg1 compounds 417:425 bioactive compounds 407:425 bioactive compounds such as alkaloids, flavonoids and polysaccharides 407:475 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 3 2 from enrichment 393:402 arg1 alkaloids 435:443 alkaloids 435:443 alkaloids 435:443 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 8 3 theme extracts 1235:1242 arg1 fingerprints 1196:1207 the fingerprints 1192:1207 the fingerprints of both ethanol and water extracts of mulberry leaves, respectively 1192:1275 SERS spectrometry was applied to characterize the fingerprints of both ethanol and water extracts of mulberry leaves, respectively. 36803175 10 4 theme application 1761:1771 arg1 potential 1773:1781 the application potential 1757:1781 the application potential of the method 1757:1795 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 3 5 theme traditional 291:301 arg1 TCM 321:323 TCM 321:323 TCM 321:323 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 3 5 theme traditional 291:301 arg1 medicine 311:318 traditional Chinese medicine 291:318 traditional Chinese medicine (TCM) 291:324 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 10 6 theme novel 1594:1598 arg1 method 1600:1605 a novel method 1592:1605 a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves 1592:1863 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 5 7 theme important 605:613 arg1 origin 592:597 geographic origin 581:597 geographic origin 581:597 Therefore, geographic origin is an important feature because it is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects. 36803175 5 7 theme important 605:613 arg1 feature 615:621 an important feature 602:621 an important feature because it is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects 602:748 Therefore, geographic origin is an important feature because it is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects. 36803175 9 8 theme origins 1441:1447 arg1 terms 1415:1419 terms 1415:1419 terms of their geographic origins 1415:1447 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 4 9 theme different 528:536 arg1 habitats 538:545 the different habitats 524:545 the different habitats of the mulberry plant 524:567 However, these components are variable due to the different habitats of the mulberry plant. 36803175 10 10 theme method 1790:1795 arg1 potential 1773:1781 the application potential 1757:1781 the application potential of the method 1757:1795 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 10 11 dep mulberry 1648:1655 arg1 leaves 1657:1662 leaves 1657:1662 leaves 1657:1662 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 9 12 theme convolutional 1490:1502 arg1 network 1511:1517 convolutional neural network 1490:1517 the deep learning algorithm convolutional neural network (CNN) 1462:1523 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 9 12 theme convolutional 1490:1502 arg1 CNN 1520:1522 CNN 1520:1522 CNN 1520:1522 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 2 13 theme medicine 264:271 arg1 systems 253:259 traditional systems 241:259 traditional systems of medicine 241:271 The leaves of Morus alba Linn., which is also known as white mulberry, have been commonly used in many of traditional systems of medicine for centuries. 36803175 10 14 theme mulberry 1648:1655 arg1 origins 1637:1643 the geographic origins 1622:1643 the geographic origins of mulberry leaves 1622:1662 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 6 15 theme overall 857:863 arg1 fingerprints 865:876 the overall fingerprints 853:876 the overall fingerprints of chemical compounds in medicinal plants 853:918 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 9 16 theme neural 1504:1509 arg1 network 1511:1517 convolutional neural network 1490:1517 the deep learning algorithm convolutional neural network (CNN) 1462:1523 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 9 16 theme neural 1504:1509 arg1 CNN 1520:1522 CNN 1520:1522 CNN 1520:1522 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 2 17 theme systems 253:259 arg1 systems 253:259 traditional systems 241:259 traditional systems of medicine 241:271 The leaves of Morus alba Linn., which is also known as white mulberry, have been commonly used in many of traditional systems of medicine for centuries. 36803175 2 17 theme systems 253:259 arg1 many 233:236 many 233:236 many 233:236 The leaves of Morus alba Linn., which is also known as white mulberry, have been commonly used in many of traditional systems of medicine for centuries. 36803175 1 18 dep surfaced 65:72 arg1 through 57:63 through 57:63 through 57:63 through surfaced enhanced Raman spectrometry and machine learning algorithms. 36803175 6 19 theme non-invasive 769:780 arg1 method 782:787 a low-cost and non-invasive method 754:787 a low-cost and non-invasive method 754:787 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 2 20 theme traditional 241:251 arg1 systems 253:259 traditional systems 241:259 traditional systems of medicine 241:271 The leaves of Morus alba Linn., which is also known as white mulberry, have been commonly used in many of traditional systems of medicine for centuries. 36803175 2 21 used used 225:228 arg2 The 135:137 The 135:137 The 135:137 The leaves of Morus alba Linn., which is also known as white mulberry, have been commonly used in many of traditional systems of medicine for centuries. 36803175 5 22 theme medicinal 718:726 arg1 qualities 728:736 medicinal qualities 718:736 medicinal qualities 718:736 Therefore, geographic origin is an important feature because it is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects. 36803175 5 23 theme geographic 581:590 arg1 origin 592:597 geographic origin 581:597 geographic origin 581:597 Therefore, geographic origin is an important feature because it is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects. 36803175 5 23 theme geographic 581:590 arg1 feature 615:621 an important feature 602:621 an important feature because it is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects 602:748 Therefore, geographic origin is an important feature because it is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects. 36803175 1 24 theme enhanced 74:81 arg1 algorithms 123:132 enhanced Raman spectrometry and machine learning algorithms 74:132 enhanced Raman spectrometry and machine learning algorithms 74:132 through surfaced enhanced Raman spectrometry and machine learning algorithms. 36803175 6 25 theme medicinal 903:911 arg1 plants 913:918 medicinal plants 903:918 medicinal plants 903:918 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 5 26 dep feature 615:621 arg1 associated 645:654 associated 645:654 is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects 634:748 Therefore, geographic origin is an important feature because it is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects. 36803175 7 27 dep mulberry 1033:1040 arg1 leaves 1042:1047 leaves 1042:1047 leaves 1042:1047 In this study, we collected mulberry leaves from five representative provinces in China, namely, Anhui, Guangdong, Hebei, Henan and Jiangsu. 36803175 6 28 theme low-cost 756:763 arg1 method 782:787 a low-cost and non-invasive method 754:787 a low-cost and non-invasive method 754:787 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 1 29 theme Raman 83:87 arg1 spectrometry 89:100 Raman spectrometry 83:100 Raman spectrometry 83:100 through surfaced enhanced Raman spectrometry and machine learning algorithms. 36803175 3 30 theme due 382:384 arg1 purpose 374:380 anti-diabetic purpose 360:380 anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides 360:475 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 10 31 with combination 1676:1686 arg1 algorithms 1726:1735 machine learning algorithms 1709:1735 machine learning algorithms 1709:1735 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 1 32 theme spectrometry 89:100 arg1 algorithms 123:132 enhanced Raman spectrometry and machine learning algorithms 74:132 enhanced Raman spectrometry and machine learning algorithms 74:132 through surfaced enhanced Raman spectrometry and machine learning algorithms. 36803175 10 33 theme quality 1804:1810 arg1 evaluation 1812:1821 the quality evaluation 1800:1821 the quality evaluation 1800:1821 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 9 34 dep mulberry 1351:1358 arg1 leaves 1360:1365 leaves 1360:1365 leaves 1360:1365 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 3 35 theme mulberry 327:334 arg1 leaf 336:339 mulberry leaf 327:339 mulberry leaf 327:339 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 6 36 dep enhanced 798:805 arg1 surface 790:796 surface 790:796 surface 790:796 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 10 37 theme geographic 1626:1635 arg1 origins 1637:1643 the geographic origins 1622:1643 the geographic origins of mulberry leaves 1622:1662 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 0 38 theme geographic 18:27 arg1 origins 29:35 geographic origins 18:35 geographic origins of Morus alba Linn 18:54 Identification of geographic origins of Morus alba Linn. 36803175 5 39 theme bioactive 661:669 arg1 composition 682:692 bioactive ingredient composition 661:692 bioactive ingredient composition that further influences medicinal qualities and effects 661:748 Therefore, geographic origin is an important feature because it is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects. 36803175 1 40 theme machine 106:112 arg1 learning 114:121 machine learning 106:121 machine learning 106:121 through surfaced enhanced Raman spectrometry and machine learning algorithms. 36803175 3 41 theme anti-diabetic 360:372 arg1 purpose 374:380 anti-diabetic purpose 360:380 anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides 360:475 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 2 42 dep Morus 149:153 arg1 Linn. 160:164 Linn. 160:164 Linn. 160:164 The leaves of Morus alba Linn., which is also known as white mulberry, have been commonly used in many of traditional systems of medicine for centuries. 36803175 2 42 dep Morus 149:153 arg1 alba 155:158 Morus alba Linn. 149:164 Morus alba Linn. 149:164 The leaves of Morus alba Linn., which is also known as white mulberry, have been commonly used in many of traditional systems of medicine for centuries. 36803175 5 43 theme ingredient 671:680 arg1 composition 682:692 bioactive ingredient composition 661:692 bioactive ingredient composition that further influences medicinal qualities and effects 661:748 Therefore, geographic origin is an important feature because it is closely associated with bioactive ingredient composition that further influences medicinal qualities and effects. 36803175 9 44 dep algorithm 1480:1488 arg1 network 1511:1517 convolutional neural network 1490:1517 the deep learning algorithm convolutional neural network (CNN) 1462:1523 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 9 44 dep algorithm 1480:1488 arg1 CNN 1520:1522 CNN 1520:1522 CNN 1520:1522 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 9 45 theme best 1536:1539 arg1 performance 1541:1551 the best performance 1532:1551 the best performance 1532:1551 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 9 46 theme learning 1471:1478 arg1 algorithm 1480:1488 the deep learning algorithm convolutional neural network (CNN) 1462:1523 the deep learning algorithm convolutional neural network (CNN) 1462:1523 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 8 47 theme SERS 1146:1149 arg1 spectrometry 1151:1162 SERS spectrometry 1146:1162 SERS spectrometry 1146:1162 SERS spectrometry was applied to characterize the fingerprints of both ethanol and water extracts of mulberry leaves, respectively. 36803175 9 48 theme SERS 1305:1308 arg1 spectra 1310:1316 SERS spectra 1305:1316 SERS spectra 1305:1316 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 6 49 theme rapid 955:959 arg1 identification 961:974 the rapid identification 951:974 the rapid identification of their geographic origins 951:1002 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 9 50 theme geographic 1430:1439 arg1 origins 1441:1447 their geographic origins 1424:1447 their geographic origins 1424:1447 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 0 51 theme origins 29:35 arg1 Identification 0:13 Identification 0:13 Identification of geographic origins of Morus alba Linn. 0:55 Identification of geographic origins of Morus alba Linn. 36803175 3 52 theme bioactive 407:415 arg1 polysaccharides 461:475 polysaccharides 461:475 polysaccharides 461:475 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 3 52 theme bioactive 407:415 arg1 flavonoids 446:455 flavonoids 446:455 flavonoids 446:455 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 3 52 theme bioactive 407:415 arg1 compounds 417:425 bioactive compounds 407:425 bioactive compounds such as alkaloids, flavonoids and polysaccharides 407:475 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 3 52 theme bioactive 407:415 arg1 alkaloids 435:443 alkaloids 435:443 alkaloids 435:443 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 0 53 theme Linn 51:54 arg1 origins 29:35 geographic origins 18:35 geographic origins of Morus alba Linn 18:54 Identification of geographic origins of Morus alba Linn. 36803175 9 54 theme spectra 1310:1316 arg1 combination 1290:1300 the combination 1286:1300 the combination of SERS spectra 1286:1316 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 9 54 theme spectra 1310:1316 arg1 learning 1330:1337 machine learning 1322:1337 machine learning 1322:1337 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 10 55 theme SERS 1691:1694 arg1 spectra 1696:1702 SERS spectra 1691:1702 SERS spectra 1691:1702 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 1 56 theme learning 114:121 arg1 algorithms 123:132 enhanced Raman spectrometry and machine learning algorithms 74:132 enhanced Raman spectrometry and machine learning algorithms 74:132 through surfaced enhanced Raman spectrometry and machine learning algorithms. 36803175 9 57 dep combination 1290:1300 arg1 algorithms 1339:1348 algorithms 1339:1348 algorithms 1339:1348 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 2 58 dep The 135:137 arg1 leaves 139:144 leaves 139:144 leaves 139:144 The leaves of Morus alba Linn., which is also known as white mulberry, have been commonly used in many of traditional systems of medicine for centuries. 36803175 3 59 used used 351:354 arg2 leaf 336:339 mulberry leaf 327:339 mulberry leaf 327:339 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 2 60 theme white 190:194 arg1 mulberry 196:203 white mulberry 190:203 white mulberry 190:203 The leaves of Morus alba Linn., which is also known as white mulberry, have been commonly used in many of traditional systems of medicine for centuries. 36803175 2 60 theme white 190:194 arg1 Morus 149:153 Morus 149:153 Morus 149:153 The leaves of Morus alba Linn., which is also known as white mulberry, have been commonly used in many of traditional systems of medicine for centuries. 36803175 7 61 theme representative 1059:1072 arg1 provinces 1074:1082 five representative provinces 1054:1082 five representative provinces 1054:1082 In this study, we collected mulberry leaves from five representative provinces in China, namely, Anhui, Guangdong, Hebei, Henan and Jiangsu. 36803175 10 62 theme mulberry 1849:1856 arg1 evaluation 1812:1821 the quality evaluation 1800:1821 the quality evaluation 1800:1821 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 10 62 theme mulberry 1849:1856 arg1 assurance 1836:1844 assurance 1836:1844 assurance 1836:1844 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 10 62 theme mulberry 1849:1856 arg1 control 1824:1830 control 1824:1830 control 1824:1830 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 8 63 theme water 1229:1233 arg1 extracts 1235:1242 both ethanol and water extracts 1212:1242 both ethanol and water extracts 1212:1242 SERS spectrometry was applied to characterize the fingerprints of both ethanol and water extracts of mulberry leaves, respectively. 36803175 10 64 theme learning 1717:1724 arg1 algorithms 1726:1735 machine learning algorithms 1709:1735 machine learning algorithms 1709:1735 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 9 65 theme machine 1322:1328 arg1 learning 1330:1337 machine learning 1322:1337 machine learning 1322:1337 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 8 66 dep mulberry 1247:1254 arg1 leaves 1256:1261 leaves 1256:1261 leaves 1256:1261 SERS spectrometry was applied to characterize the fingerprints of both ethanol and water extracts of mulberry leaves, respectively. 36803175 6 67 theme geographic 985:994 arg1 origins 996:1002 their geographic origins 979:1002 their geographic origins 979:1002 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 8 68 theme mulberry 1247:1254 arg1 extracts 1235:1242 both ethanol and water extracts 1212:1242 both ethanol and water extracts 1212:1242 SERS spectrometry was applied to characterize the fingerprints of both ethanol and water extracts of mulberry leaves, respectively. 36803175 4 69 theme plant 563:567 arg1 habitats 538:545 the different habitats 524:545 the different habitats of the mulberry plant 524:567 However, these components are variable due to the different habitats of the mulberry plant. 36803175 6 70 from plants 913:918 arg1 fingerprints 865:876 the overall fingerprints 853:876 the overall fingerprints of chemical compounds in medicinal plants 853:918 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 6 71 theme Raman 807:811 arg1 spectrometry 813:824 surface enhanced Raman spectrometry 790:824 surface enhanced Raman spectrometry (SERS) 790:831 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 6 71 theme Raman 807:811 arg1 SERS 827:830 SERS 827:830 SERS 827:830 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 10 72 theme machine 1709:1715 arg1 learning 1717:1724 machine learning 1709:1724 machine learning algorithms 1709:1735 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 9 73 from accuracies 1401:1410 arg1 terms 1415:1419 terms 1415:1419 terms of their geographic origins 1415:1447 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 9 74 theme deep 1466:1469 arg1 algorithm 1480:1488 the deep learning algorithm convolutional neural network (CNN) 1462:1523 the deep learning algorithm convolutional neural network (CNN) 1462:1523 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 4 75 theme mulberry 554:561 arg1 plant 563:567 the mulberry plant 550:567 the mulberry plant 550:567 However, these components are variable due to the different habitats of the mulberry plant. 36803175 3 76 theme Chinese 303:309 arg1 TCM 321:323 TCM 321:323 TCM 321:323 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 3 76 theme Chinese 303:309 arg1 medicine 311:318 traditional Chinese medicine 291:318 traditional Chinese medicine (TCM) 291:324 In traditional Chinese medicine (TCM), mulberry leaf is mainly used for anti-diabetic purpose due to its enrichment in bioactive compounds such as alkaloids, flavonoids and polysaccharides. 36803175 6 77 theme enhanced 798:805 arg1 spectrometry 813:824 surface enhanced Raman spectrometry 790:824 surface enhanced Raman spectrometry (SERS) 790:831 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 6 77 theme enhanced 798:805 arg1 SERS 827:830 SERS 827:830 SERS 827:830 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 8 78 theme ethanol 1217:1223 arg1 extracts 1235:1242 both ethanol and water extracts 1212:1242 both ethanol and water extracts 1212:1242 SERS spectrometry was applied to characterize the fingerprints of both ethanol and water extracts of mulberry leaves, respectively. 36803175 9 79 theme high 1396:1399 arg1 accuracies 1401:1410 high accuracies 1396:1410 high accuracies in terms of their geographic origins 1396:1447 Through the combination of SERS spectra and machine learning algorithms, mulberry leaves were well discriminated with high accuracies in terms of their geographic origins, among which the deep learning algorithm convolutional neural network (CNN) showed the best performance. 36803175 6 80 from fingerprints 865:876 arg1 plants 913:918 medicinal plants 903:918 medicinal plants 903:918 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 6 81 theme compounds 890:898 arg1 fingerprints 865:876 the overall fingerprints 853:876 the overall fingerprints of chemical compounds in medicinal plants 853:918 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 10 82 theme spectra 1696:1702 arg1 combination 1676:1686 the combination 1672:1686 the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves 1672:1863 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36803175 6 83 theme origins 996:1002 arg1 identification 961:974 the rapid identification 951:974 the rapid identification of their geographic origins 951:1002 As a low-cost and non-invasive method, surface enhanced Raman spectrometry (SERS) is able to generate the overall fingerprints of chemical compounds in medicinal plants, which holds the potential for the rapid identification of their geographic origins. 36803175 10 84 dep mulberry 1849:1856 arg1 leaves 1858:1863 leaves 1858:1863 leaves 1858:1863 Taken together, our study established a novel method for predicting the geographic origins of mulberry leaves through the combination of SERS spectra with machine learning algorithms, which strengthened the application potential of the method in the quality evaluation, control and assurance of mulberry leaves. 36615553 8 0 theme cell 1411:1414 arg1 line 1416:1419 any cell line 1407:1419 any cell line 1407:1419 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 6 1 theme phenolic 949:956 arg1 atractyloside 1059:1071 atractyloside 1059:1071 atractyloside 1059:1071 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 1 theme phenolic 949:956 arg1 acid 992:995 gallic acid 985:995 gallic acid 985:995 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 1 theme phenolic 949:956 arg1 acid 1033:1036 liquidambaric acid 1019:1036 liquidambaric acid 1019:1036 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 1 theme phenolic 949:956 arg1 acids 958:962 phenolic acids 949:962 phenolic acids 949:962 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 1 theme phenolic 949:956 arg1 combretastatin 1039:1052 combretastatin 1039:1052 combretastatin 1039:1052 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 1 theme phenolic 949:956 arg1 acid 1013:1016 protocathecuic acid 998:1016 protocathecuic acid 998:1016 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 0 2 theme Potential 76:84 arg1 Evaluation 9:18 Chemical Evaluation 0:18 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 0:105 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 36615553 5 3 from carbohydrates 692:704 arg1 proportions 719:729 different proportions 709:729 different proportions 709:729 The three extracts were composed of proteins, phenolic compounds, and carbohydrates in different proportions. 36615553 2 4 theme biological 334:343 arg1 potential 345:353 biological potential 334:353 biological potential 334:353 The present study was designed to investigate the chemical composition and biological potential of extracts obtained from the fruits of this plant. 36615553 7 5 theme S-EA 1238:1241 arg1 > 1243:1245 the sequence S-EA > 1225:1245 the sequence S-EA > EA > P-EA 1225:1259 The cytotoxicity followed the sequence S-EA > EA > P-EA, demonstrating that the toxic compounds were separated from the non-toxic ones by ethanol precipitation. 36615553 6 6 theme µg/mL 1178:1182 arg1 values 1134:1139 IC50 values 1129:1139 IC50 values 1129:1139 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 3 7 theme plus 486:489 arg1 NMR 491:493 plus NMR 486:493 plus NMR 486:493 For the chemical evaluation, it was used mainly liquid and gas chromatography, plus NMR, and colorimetric methods. 36615553 3 8 theme colorimetric 500:511 arg1 methods 513:519 colorimetric methods 500:519 colorimetric methods 500:519 For the chemical evaluation, it was used mainly liquid and gas chromatography, plus NMR, and colorimetric methods. 36615553 7 9 theme non-toxic 1325:1333 arg1 ones 1335:1338 the non-toxic ones 1321:1338 the non-toxic ones 1321:1338 The cytotoxicity followed the sequence S-EA > EA > P-EA, demonstrating that the toxic compounds were separated from the non-toxic ones by ethanol precipitation. 36615553 1 10 theme skin 247:250 arg1 sores 252:256 diarrhea, dysentery, coughs, and skin sores 214:256 diarrhea, dysentery, coughs, and skin sores 214:256 Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. 36615553 0 11 theme Anticancer 89:98 arg1 Drugs 100:104 Anticancer Drugs 89:104 Anticancer Drugs 89:104 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 36615553 7 12 theme ethanol 1343:1349 arg1 precipitation 1351:1363 ethanol precipitation 1343:1363 ethanol precipitation 1343:1363 The cytotoxicity followed the sequence S-EA > EA > P-EA, demonstrating that the toxic compounds were separated from the non-toxic ones by ethanol precipitation. 36615553 6 13 theme antioxidant 1102:1112 arg1 activity 1114:1121 antioxidant activity 1102:1121 antioxidant activity 1102:1121 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 2 14 theme present 263:269 arg1 study 271:275 The present study 259:275 The present study 259:275 The present study was designed to investigate the chemical composition and biological potential of extracts obtained from the fruits of this plant. 36615553 6 15 contain contained 791:799 arg2 methyl 848:853 methyl 848:853 methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively 848:1196 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 15 contain contained 791:799 arg1 P-EA 785:788 P-EA 785:788 P-EA 785:788 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 15 contain contained 791:799 arg2 acetylated 833:842 acetylated 833:842 acetylated 833:842 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 15 contain contained 791:799 arg1 extract 776:782 the polysaccharide extract 757:782 the polysaccharide extract (P-EA) 757:789 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 15 contain contained 791:799 arg2 polysaccharides 808:822 pectic polysaccharides 801:822 pectic polysaccharides 801:822 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 16 theme liquidambaric 1019:1031 arg1 acid 1033:1036 liquidambaric acid 1019:1036 liquidambaric acid 1019:1036 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 8 17 theme normal 1554:1559 arg1 cells 1561:1565 normal cells 1554:1565 normal cells 1554:1565 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 3 18 theme chemical 415:422 arg1 evaluation 424:433 the chemical evaluation 411:433 the chemical evaluation 411:433 For the chemical evaluation, it was used mainly liquid and gas chromatography, plus NMR, and colorimetric methods. 36615553 6 19 theme fraction 925:932 arg1 S-EA 934:937 the fraction S-EA 921:937 the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA 921:1093 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 20 theme pectic 801:806 arg1 acetylated 833:842 acetylated 833:842 acetylated 833:842 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 20 theme pectic 801:806 arg1 polysaccharides 808:822 pectic polysaccharides 801:822 pectic polysaccharides 801:822 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 20 theme pectic 801:806 arg1 methyl 848:853 methyl 848:853 methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively 848:1196 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 21 theme µg/mL 1162:1166 arg1 values 1134:1139 IC50 values 1129:1139 IC50 values 1129:1139 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 1 22 theme traditional 176:186 arg1 medicine 196:203 traditional Chinese medicine 176:203 traditional Chinese medicine 176:203 Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. 36615553 0 23 theme Chemical 0:7 arg1 Evaluation 9:18 Chemical Evaluation 0:18 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 0:105 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 36615553 1 24 theme Chinese 188:194 arg1 medicine 196:203 traditional Chinese medicine 176:203 traditional Chinese medicine 176:203 Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. 36615553 0 25 theme Liquidambar 23:33 arg1 Extracts 57:64 Liquidambar styraciflua L. Fruits Extracts 23:64 Liquidambar styraciflua L. Fruits Extracts 23:64 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 36615553 7 26 dep > 1243:1245 arg1 > 1251:1253 EA > 1248:1253 the sequence S-EA > EA > P-EA 1225:1259 The cytotoxicity followed the sequence S-EA > EA > P-EA, demonstrating that the toxic compounds were separated from the non-toxic ones by ethanol precipitation. 36615553 7 26 dep > 1243:1245 arg1 P-EA 1256:1259 P-EA 1256:1259 the sequence S-EA > EA > P-EA 1225:1259 The cytotoxicity followed the sequence S-EA > EA > P-EA, demonstrating that the toxic compounds were separated from the non-toxic ones by ethanol precipitation. 36615553 3 27 used used 443:446 arg2 it 436:437 it 436:437 it 436:437 For the chemical evaluation, it was used mainly liquid and gas chromatography, plus NMR, and colorimetric methods. 36615553 5 28 from proteins 658:665 arg1 proportions 719:729 different proportions 709:729 different proportions 709:729 The three extracts were composed of proteins, phenolic compounds, and carbohydrates in different proportions. 36615553 2 29 dep composition 318:328 arg1 the 305:307 the 305:307 the 305:307 The present study was designed to investigate the chemical composition and biological potential of extracts obtained from the fruits of this plant. 36615553 2 30 theme plant 400:404 arg1 fruits 385:390 the fruits 381:390 the fruits of this plant 381:404 The present study was designed to investigate the chemical composition and biological potential of extracts obtained from the fruits of this plant. 36615553 0 31 theme L. 47:48 arg1 Extracts 57:64 Liquidambar styraciflua L. Fruits Extracts 23:64 Liquidambar styraciflua L. Fruits Extracts 23:64 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 36615553 4 32 theme aqueous 526:532 arg1 EA 543:544 EA 543:544 EA 543:544 The aqueous extract (EA) originated two other fractions: an aqueous (P-EA) and an ethanolic (S-EA). 36615553 4 32 theme aqueous 526:532 arg1 extract 534:540 The aqueous extract 522:540 The aqueous extract (EA) 522:545 The aqueous extract (EA) originated two other fractions: an aqueous (P-EA) and an ethanolic (S-EA). 36615553 6 33 theme protocathecuic 998:1011 arg1 acid 1013:1016 protocathecuic acid 998:1016 protocathecuic acid 998:1016 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 34 theme gallic 985:990 arg1 acid 992:995 gallic acid 985:995 gallic acid 985:995 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 0 35 theme styraciflua 35:45 arg1 Extracts 57:64 Liquidambar styraciflua L. Fruits Extracts 23:64 Liquidambar styraciflua L. Fruits Extracts 23:64 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 36615553 6 36 theme µg/mL 1149:1153 arg1 values 1134:1139 IC50 values 1129:1139 IC50 values 1129:1139 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 1 37 theme diarrhea 214:221 arg1 sores 252:256 diarrhea, dysentery, coughs, and skin sores 214:256 diarrhea, dysentery, coughs, and skin sores 214:256 Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. 36615553 0 38 theme Extracts 57:64 arg1 Evaluation 9:18 Chemical Evaluation 0:18 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 0:105 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 36615553 6 39 theme polysaccharide 761:774 arg1 P-EA 785:788 P-EA 785:788 P-EA 785:788 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 39 theme polysaccharide 761:774 arg1 extract 776:782 the polysaccharide extract 757:782 the polysaccharide extract (P-EA) 757:789 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 8 40 theme high 1503:1506 arg1 toxicity 1508:1515 its high toxicity 1499:1515 its high toxicity to tumoral cells 1499:1532 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 0 41 theme Fruits 50:55 arg1 Extracts 57:64 Liquidambar styraciflua L. Fruits Extracts 23:64 Liquidambar styraciflua L. Fruits Extracts 23:64 Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs. 36615553 7 42 theme sequence 1229:1236 arg1 > 1243:1245 the sequence S-EA > 1225:1245 the sequence S-EA > EA > P-EA 1225:1259 The cytotoxicity followed the sequence S-EA > EA > P-EA, demonstrating that the toxic compounds were separated from the non-toxic ones by ethanol precipitation. 36615553 8 43 theme fraction 1426:1433 arg1 P-EA 1435:1438 the fraction P-EA 1422:1438 the fraction P-EA 1422:1438 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 8 43 theme fraction 1426:1433 arg1 candidate 1455:1463 a promising candidate 1443:1463 a promising candidate for studies against cancer 1443:1490 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 4 44 dep fractions 568:576 arg1 S-EA 615:618 S-EA 615:618 S-EA 615:618 The aqueous extract (EA) originated two other fractions: an aqueous (P-EA) and an ethanolic (S-EA). 36615553 4 44 dep fractions 568:576 arg1 P-EA 591:594 P-EA 591:594 P-EA 591:594 The aqueous extract (EA) originated two other fractions: an aqueous (P-EA) and an ethanolic (S-EA). 36615553 4 44 dep fractions 568:576 arg1 aqueous 582:588 aqueous 582:588 aqueous 582:588 The aqueous extract (EA) originated two other fractions: an aqueous (P-EA) and an ethanolic (S-EA). 36615553 4 44 dep fractions 568:576 arg1 ethanolic 604:612 ethanolic 604:612 ethanolic 604:612 The aqueous extract (EA) originated two other fractions: an aqueous (P-EA) and an ethanolic (S-EA). 36615553 3 45 theme gas 466:468 arg1 chromatography 470:483 liquid and gas chromatography 455:483 chromatography 470:483 For the chemical evaluation, it was used mainly liquid and gas chromatography, plus NMR, and colorimetric methods. 36615553 8 46 theme promising 1445:1453 arg1 P-EA 1435:1438 the fraction P-EA 1422:1438 the fraction P-EA 1422:1438 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 8 46 theme promising 1445:1453 arg1 candidate 1455:1463 a promising candidate 1443:1463 a promising candidate for studies against cancer 1443:1490 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 1 47 theme aromatic 140:147 arg1 species 149:155 an aromatic species 137:155 an aromatic species 137:155 Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. 36615553 1 47 theme aromatic 140:147 arg1 L. 131:132 L. 131:132 L. 131:132 Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. 36615553 2 48 theme chemical 309:316 arg1 composition 318:328 chemical composition 309:328 chemical composition 309:328 The present study was designed to investigate the chemical composition and biological potential of extracts obtained from the fruits of this plant. 36615553 4 49 theme other 562:566 arg1 fractions 568:576 two other fractions 558:576 two other fractions: an aqueous (P-EA) and an ethanolic (S-EA) 558:619 The aqueous extract (EA) originated two other fractions: an aqueous (P-EA) and an ethanolic (S-EA). 36615553 8 50 theme fraction 1376:1383 arg1 S-EA 1385:1388 the fraction S-EA 1372:1388 the fraction S-EA 1372:1388 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 8 50 theme fraction 1376:1383 arg1 toxic 1398:1402 toxic 1398:1402 toxic 1398:1402 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 6 51 theme IC50 1129:1132 arg1 values 1134:1139 IC50 values 1129:1139 IC50 values 1129:1139 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 3 52 theme liquid 455:460 arg1 chromatography 470:483 liquid and gas chromatography 455:483 chromatography 470:483 For the chemical evaluation, it was used mainly liquid and gas chromatography, plus NMR, and colorimetric methods. 36615553 1 53 theme dysentery 224:232 arg1 sores 252:256 diarrhea, dysentery, coughs, and skin sores 214:256 diarrhea, dysentery, coughs, and skin sores 214:256 Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. 36615553 5 54 theme phenolic 668:675 arg1 compounds 677:685 phenolic compounds 668:685 phenolic compounds 668:685 The three extracts were composed of proteins, phenolic compounds, and carbohydrates in different proportions. 36615553 5 55 from compounds 677:685 arg1 proportions 719:729 different proportions 709:729 different proportions 709:729 The three extracts were composed of proteins, phenolic compounds, and carbohydrates in different proportions. 36615553 8 56 theme low 1538:1540 arg1 toxicity 1542:1549 low toxicity 1538:1549 low toxicity to normal cells 1538:1565 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 2 57 theme extracts 358:365 arg1 composition 318:328 chemical composition 309:328 chemical composition 309:328 The present study was designed to investigate the chemical composition and biological potential of extracts obtained from the fruits of this plant. 36615553 2 57 theme extracts 358:365 arg1 potential 345:353 biological potential 334:353 biological potential 334:353 The present study was designed to investigate the chemical composition and biological potential of extracts obtained from the fruits of this plant. 36615553 8 58 theme tumoral 1520:1526 arg1 cells 1528:1532 tumoral cells 1520:1532 tumoral cells 1520:1532 While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. 36615553 5 59 theme different 709:717 arg1 proportions 719:729 different proportions 709:729 different proportions 709:729 The three extracts were composed of proteins, phenolic compounds, and carbohydrates in different proportions. 36615553 6 60 dep S-EA 934:937 arg1 A. 1073:1074 the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA 921:1093 the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA 921:1093 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 60 dep S-EA 934:937 arg1 P-EA 1080:1083 P-EA 1080:1083 P-EA 1080:1083 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 60 dep S-EA 934:937 arg1 S-EA 1090:1093 S-EA 1090:1093 S-EA 1090:1093 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 6 60 dep S-EA 934:937 arg1 EA 1076:1077 EA 1076:1077 EA 1076:1077 The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. 36615553 7 61 theme EA 1248:1249 arg1 > 1251:1253 EA > 1248:1253 the sequence S-EA > EA > P-EA 1225:1259 The cytotoxicity followed the sequence S-EA > EA > P-EA, demonstrating that the toxic compounds were separated from the non-toxic ones by ethanol precipitation. 36615553 7 62 theme toxic 1285:1289 arg1 compounds 1291:1299 the toxic compounds 1281:1299 the toxic compounds 1281:1299 The cytotoxicity followed the sequence S-EA > EA > P-EA, demonstrating that the toxic compounds were separated from the non-toxic ones by ethanol precipitation. 36615553 1 63 theme coughs 235:240 arg1 sores 252:256 diarrhea, dysentery, coughs, and skin sores 214:256 diarrhea, dysentery, coughs, and skin sores 214:256 Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. 35626955 6 0 from composition 1000:1010 arg1 rats 1091:1094 Sprague Dawley rats 1076:1094 Sprague Dawley rats 1076:1094 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 7 1 theme ± 1264:1264 arg1 carbohydrates 1272:1284 38.96 ± 4.60% carbohydrates 1258:1284 38.96 ± 4.60% carbohydrates 1258:1284 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 10 2 theme mycelia 1948:1954 arg1 NOAEL 1935:1939 NOAEL 1935:1939 NOAEL 1935:1939 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 2 theme mycelia 1948:1954 arg1 food 2032:2035 a novel food 2024:2035 a novel food at the NOAEL 2024:2048 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 2 theme mycelia 1948:1954 arg1 level 1928:1932 the no-observed-adverse-effects level 1896:1932 the no-observed-adverse-effects level (NOAEL) of ME mycelia 1896:1954 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 2 theme mycelia 1948:1954 arg1 mg/kg/day 1978:1986 greater than 3000 mg/kg/day 1960:1986 greater than 3000 mg/kg/day 1960:1986 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 6 3 theme Dawley 1084:1089 arg1 rats 1091:1094 Sprague Dawley rats 1076:1094 Sprague Dawley rats 1076:1094 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 5 4 theme esculenta 777:785 arg1 mycelia 787:793 M. esculenta mycelia to be used as an innovative food ingredient 774:837 M. esculenta mycelia to be used as an innovative food ingredient 774:837 However, for M. esculenta mycelia to be used as an innovative food ingredient, it is very important to prove it is safe for human consumption while providing high-quality nutrients. 35626955 1 5 theme morel 151:155 arg1 mushrooms 157:165 "true" morel mushrooms 144:165 "true" morel mushrooms 144:165 Morchella esculenta (ME), or "true" morel mushrooms, are one of the most expensive mushrooms. 35626955 7 6 theme crude 1243:1247 arg1 protein 1249:1255 crude protein 1243:1255 39.35 ± 0.35% crude protein 1229:1255 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 3 7 theme esculenta 555:563 arg1 difficult 582:590 difficult 582:590 difficult 582:590 However, the M. esculenta fruiting body is difficult to collect in nature and the quality is not always reliable. 35626955 3 7 theme esculenta 555:563 arg1 body 574:577 the M. esculenta fruiting body 548:577 the M. esculenta fruiting body 548:577 However, the M. esculenta fruiting body is difficult to collect in nature and the quality is not always reliable. 35626955 7 8 theme 0.35 1237:1240 arg1 ± 1235:1235 ± 1235:1235 ± 1235:1235 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 9 theme 39.35 1229:1233 arg1 ± 1235:1235 ± 1235:1235 ± 1235:1235 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 8 10 theme mg/kg 1545:1549 arg1 doses 1512:1516 oral doses 1507:1516 oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days 1507:1561 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 9 11 theme organ 1744:1748 arg1 weights 1750:1756 organ weights 1744:1756 organ weights 1744:1756 Although there were alterations in hematological and biochemical parameters, organ weights, necropsy findings, and histological markers, they were not considered to be toxicologically significant. 35626955 9 12 from alterations 1687:1697 arg1 weights 1750:1756 organ weights 1744:1756 organ weights 1744:1756 Although there were alterations in hematological and biochemical parameters, organ weights, necropsy findings, and histological markers, they were not considered to be toxicologically significant. 35626955 9 12 from alterations 1687:1697 arg1 findings 1768:1775 necropsy findings 1759:1775 necropsy findings 1759:1775 Although there were alterations in hematological and biochemical parameters, organ weights, necropsy findings, and histological markers, they were not considered to be toxicologically significant. 35626955 9 12 from alterations 1687:1697 arg1 markers 1795:1801 histological markers 1782:1801 histological markers 1782:1801 Although there were alterations in hematological and biochemical parameters, organ weights, necropsy findings, and histological markers, they were not considered to be toxicologically significant. 35626955 9 12 from alterations 1687:1697 arg1 parameters 1732:1741 parameters 1732:1741 parameters 1732:1741 Although there were alterations in hematological and biochemical parameters, organ weights, necropsy findings, and histological markers, they were not considered to be toxicologically significant. 35626955 7 13 theme ME 1134:1135 arg1 mycelia 1137:1143 the ME mycelia 1130:1143 the ME mycelia 1130:1143 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 14 contain contained 1145:1153 arg1 mycelia 1137:1143 the ME mycelia 1130:1143 the ME mycelia 1130:1143 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 14 contain contained 1145:1153 arg2 % 1189:1189 0.32 ± 0.07% 1178:1189 0.32 ± 0.07% total ash 1178:1199 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 14 contain contained 1145:1153 arg2 % 1166:1166 4.20 ± 0.49% 1155:1166 4.20 ± 0.49% moisture 1155:1175 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 14 contain contained 1145:1153 arg2 % 1241:1241 39.35 ± 0.35% 1229:1241 39.35 ± 0.35% crude protein 1229:1255 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 14 contain contained 1145:1153 arg2 % 1214:1214 17.17 ± 0.07% 1202:1214 17.17 ± 0.07% crude lipid 1202:1226 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 14 contain contained 1145:1153 arg2 carbohydrates 1272:1284 38.96 ± 4.60% carbohydrates 1258:1284 38.96 ± 4.60% carbohydrates 1258:1284 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 14 contain contained 1145:1153 arg2 energy 1316:1321 467.77 ± 0.21 kcal/100 g energy 1291:1321 467.77 ± 0.21 kcal/100 g energy 1291:1321 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 2 15 theme M. 209:210 arg1 esculenta 212:220 M. esculenta 209:220 M. esculenta 209:220 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 8 16 theme significant 1573:1583 arg1 changes 1585:1591 no significant changes 1570:1591 no significant changes 1570:1591 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 7 17 dep % 1241:1241 arg1 protein 1249:1255 crude protein 1243:1255 39.35 ± 0.35% crude protein 1229:1255 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 18 theme Reference 1397:1405 arg1 Intakes 1407:1413 Dietary Reference Intakes 1389:1413 Dietary Reference Intakes 1389:1413 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 1 19 theme true 145:148 arg1 mushrooms 157:165 "true" morel mushrooms 144:165 "true" morel mushrooms 144:165 Morchella esculenta (ME), or "true" morel mushrooms, are one of the most expensive mushrooms. 35626955 7 20 dep % 1166:1166 arg1 moisture 1168:1175 moisture 1168:1175 4.20 ± 0.49% moisture 1155:1175 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 21 theme 17.17 1202:1206 arg1 ± 1208:1208 ± 1208:1208 ± 1208:1208 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 6 22 from rats 1091:1094 arg1 composition 1000:1010 the nutritional composition 984:1010 the nutritional composition 984:1010 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 6 22 from rats 1091:1094 arg1 days 1027:1030 90 days 1024:1030 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats 1024:1094 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 0 23 theme Nutrition 0:8 arg1 Profile 10:16 Nutrition Profile 0:16 Nutrition Profile 0:16 Nutrition Profile and Animal-Tested Safety of Morchella esculenta Mycelia Produced by Fermentation in Bioreactors. 35626955 8 24 theme body 1623:1626 arg1 signs 1616:1620 clinical signs 1607:1620 clinical signs 1607:1620 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 8 24 theme body 1623:1626 arg1 weight 1628:1633 body weight 1623:1633 body weight 1623:1633 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 7 25 dep contained 1145:1153 arg1 provides 1330:1337 provides 1330:1337 provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend 1330:1423 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 6 26 theme nutritional 988:998 arg1 composition 1000:1010 the nutritional composition 984:1010 the nutritional composition 984:1010 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 4 27 theme useful 714:719 arg1 alternative 721:731 a useful alternative 712:731 a useful alternative for large-scale production 712:758 For this reason, the cultivation of its mycelia represents a useful alternative for large-scale production. 35626955 2 28 theme polyphenolic 394:405 arg1 compounds 407:415 polyphenolic compounds 394:415 polyphenolic compounds 394:415 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 1 29 theme Morchella 115:123 arg1 ME 136:137 ME 136:137 ME 136:137 Morchella esculenta (ME), or "true" morel mushrooms, are one of the most expensive mushrooms. 35626955 1 29 theme Morchella 115:123 arg1 esculenta 125:133 Morchella esculenta 115:133 Morchella esculenta (ME) 115:138 Morchella esculenta (ME), or "true" morel mushrooms, are one of the most expensive mushrooms. 35626955 5 30 theme innovative 812:821 arg1 ingredient 828:837 an innovative food ingredient 809:837 an innovative food ingredient 809:837 However, for M. esculenta mycelia to be used as an innovative food ingredient, it is very important to prove it is safe for human consumption while providing high-quality nutrients. 35626955 7 31 theme Dietary 1389:1395 arg1 Intakes 1407:1413 Dietary Reference Intakes 1389:1413 Dietary Reference Intakes 1389:1413 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 10 32 from NOAEL 2044:2048 arg1 food 2032:2035 a novel food 2024:2035 a novel food at the NOAEL 2024:2048 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 32 from NOAEL 2044:2048 arg1 level 1928:1932 the no-observed-adverse-effects level 1896:1932 the no-observed-adverse-effects level (NOAEL) of ME mycelia 1896:1954 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 0 33 theme Mycelia 66:72 arg1 Profile 10:16 Nutrition Profile 0:16 Nutrition Profile 0:16 Nutrition Profile and Animal-Tested Safety of Morchella esculenta Mycelia Produced by Fermentation in Bioreactors. 35626955 0 33 theme Mycelia 66:72 arg1 Safety 36:41 Animal-Tested Safety 22:41 Animal-Tested Safety 22:41 Nutrition Profile and Animal-Tested Safety of Morchella esculenta Mycelia Produced by Fermentation in Bioreactors. 35626955 0 34 theme Morchella 46:54 arg1 Mycelia 66:72 Morchella esculenta Mycelia 46:72 Morchella esculenta Mycelia 46:72 Nutrition Profile and Animal-Tested Safety of Morchella esculenta Mycelia Produced by Fermentation in Bioreactors. 35626955 6 35 theme toxicity 1040:1047 arg1 composition 1000:1010 the nutritional composition 984:1010 the nutritional composition 984:1010 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 6 35 theme toxicity 1040:1047 arg1 days 1027:1030 90 days 1024:1030 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats 1024:1094 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 6 36 from toxicity 1040:1047 arg1 rats 1091:1094 Sprague Dawley rats 1076:1094 Sprague Dawley rats 1076:1094 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 2 37 theme fatty 309:313 arg1 acids 315:319 polyunsaturated fatty acids 293:319 polyunsaturated fatty acids 293:319 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 37 theme fatty 309:313 arg1 polysaccharides 362:376 polysaccharides 362:376 polysaccharides 362:376 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 37 theme fatty 309:313 arg1 compounds 407:415 polyphenolic compounds 394:415 polyphenolic compounds 394:415 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 37 theme fatty 309:313 arg1 tocopherols 422:432 tocopherols 422:432 tocopherols 422:432 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 37 theme fatty 309:313 arg1 acids 387:391 organic acids 379:391 organic acids 379:391 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 8 38 theme Dawley 1466:1471 arg1 rats 1473:1476 forty male and female Sprague Dawley rats 1436:1476 forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days 1436:1561 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 7 39 theme g 1314:1314 arg1 energy 1316:1321 467.77 ± 0.21 kcal/100 g energy 1291:1321 467.77 ± 0.21 kcal/100 g energy 1291:1321 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 5 40 theme food 823:826 arg1 ingredient 828:837 an innovative food ingredient 809:837 an innovative food ingredient 809:837 However, for M. esculenta mycelia to be used as an innovative food ingredient, it is very important to prove it is safe for human consumption while providing high-quality nutrients. 35626955 1 41 theme mushrooms 198:206 arg1 mushrooms 198:206 the most expensive mushrooms 179:206 the most expensive mushrooms 179:206 Morchella esculenta (ME), or "true" morel mushrooms, are one of the most expensive mushrooms. 35626955 1 41 theme mushrooms 198:206 arg1 one 172:174 one 172:174 one 172:174 Morchella esculenta (ME), or "true" morel mushrooms, are one of the most expensive mushrooms. 35626955 7 42 dep % 1189:1189 arg1 ash 1197:1199 total ash 1191:1199 0.32 ± 0.07% total ash 1178:1199 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 2 43 theme several 326:332 arg1 polysaccharides 362:376 polysaccharides 362:376 polysaccharides 362:376 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 43 theme several 326:332 arg1 acids 387:391 organic acids 379:391 organic acids 379:391 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 43 theme several 326:332 arg1 compounds 407:415 polyphenolic compounds 394:415 polyphenolic compounds 394:415 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 43 theme several 326:332 arg1 tocopherols 422:432 tocopherols 422:432 tocopherols 422:432 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 43 theme several 326:332 arg1 compounds 344:352 several bioactive compounds 326:352 several bioactive compounds 326:352 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 8 44 theme male 1442:1445 arg1 rats 1473:1476 forty male and female Sprague Dawley rats 1436:1476 forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days 1436:1561 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 8 45 theme oral 1507:1510 arg1 doses 1512:1516 oral doses 1507:1516 oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days 1507:1561 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 2 46 contain contain 222:228 arg1 esculenta 212:220 M. esculenta 209:220 M. esculenta 209:220 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 46 contain contain 222:228 arg2 nutrients 248:256 the important nutrients 234:256 all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications 230:536 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 10 47 theme novel 2026:2030 arg1 food 2032:2035 a novel food 2024:2035 a novel food at the NOAEL 2024:2048 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 47 theme novel 2026:2030 arg1 level 1928:1932 the no-observed-adverse-effects level 1896:1932 the no-observed-adverse-effects level (NOAEL) of ME mycelia 1896:1954 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 7 48 theme 4.60 1266:1269 arg1 % 1270:1270 % 1270:1270 % 1270:1270 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 10 49 theme no-observed-adverse-effects 1900:1926 arg1 NOAEL 1935:1939 NOAEL 1935:1939 NOAEL 1935:1939 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 49 theme no-observed-adverse-effects 1900:1926 arg1 food 2032:2035 a novel food 2024:2035 a novel food at the NOAEL 2024:2048 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 49 theme no-observed-adverse-effects 1900:1926 arg1 level 1928:1932 the no-observed-adverse-effects level 1896:1932 the no-observed-adverse-effects level (NOAEL) of ME mycelia 1896:1954 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 49 theme no-observed-adverse-effects 1900:1926 arg1 mg/kg/day 1978:1986 greater than 3000 mg/kg/day 1960:1986 greater than 3000 mg/kg/day 1960:1986 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 8 50 theme female 1451:1456 arg1 rats 1473:1476 forty male and female Sprague Dawley rats 1436:1476 forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days 1436:1561 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 2 51 theme important 238:246 arg1 nutrients 248:256 the important nutrients 234:256 all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications 230:536 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 1 52 theme " 149:149 arg1 mushrooms 157:165 "true" morel mushrooms 144:165 "true" morel mushrooms 144:165 Morchella esculenta (ME), or "true" morel mushrooms, are one of the most expensive mushrooms. 35626955 7 53 theme % 1270:1270 arg1 carbohydrates 1272:1284 38.96 ± 4.60% carbohydrates 1258:1284 38.96 ± 4.60% carbohydrates 1258:1284 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 3 54 theme M. 552:553 arg1 difficult 582:590 difficult 582:590 difficult 582:590 However, the M. esculenta fruiting body is difficult to collect in nature and the quality is not always reliable. 35626955 3 54 theme M. 552:553 arg1 body 574:577 the M. esculenta fruiting body 548:577 the M. esculenta fruiting body 548:577 However, the M. esculenta fruiting body is difficult to collect in nature and the quality is not always reliable. 35626955 6 55 theme mycelia 1065:1071 arg1 toxicity 1040:1047 oral toxicity 1035:1047 oral toxicity of fermented ME mycelia in Sprague Dawley rats 1035:1094 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 9 56 theme hematological 1702:1714 arg1 parameters 1732:1741 parameters 1732:1741 parameters 1732:1741 Although there were alterations in hematological and biochemical parameters, organ weights, necropsy findings, and histological markers, they were not considered to be toxicologically significant. 35626955 0 57 from Fermentation 86:97 arg1 Bioreactors 102:112 Bioreactors 102:112 Bioreactors 102:112 Nutrition Profile and Animal-Tested Safety of Morchella esculenta Mycelia Produced by Fermentation in Bioreactors. 35626955 6 58 theme fermented 1052:1060 arg1 mycelia 1065:1071 fermented ME mycelia 1052:1071 fermented ME mycelia 1052:1071 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 9 59 theme biochemical 1720:1730 arg1 parameters 1732:1741 parameters 1732:1741 parameters 1732:1741 Although there were alterations in hematological and biochemical parameters, organ weights, necropsy findings, and histological markers, they were not considered to be toxicologically significant. 35626955 7 60 dep % 1214:1214 arg1 lipid 1222:1226 crude lipid 1216:1226 17.17 ± 0.07% crude lipid 1202:1226 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 2 61 theme anti-inflammatory 507:523 arg1 applications 525:536 anti-inflammatory applications 507:536 anti-inflammatory applications 507:536 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 3 62 theme fruiting 565:572 arg1 difficult 582:590 difficult 582:590 difficult 582:590 However, the M. esculenta fruiting body is difficult to collect in nature and the quality is not always reliable. 35626955 3 62 theme fruiting 565:572 arg1 body 574:577 the M. esculenta fruiting body 548:577 the M. esculenta fruiting body 548:577 However, the M. esculenta fruiting body is difficult to collect in nature and the quality is not always reliable. 35626955 10 63 theme ME 1945:1946 arg1 mycelia 1948:1954 ME mycelia 1945:1954 ME mycelia 1945:1954 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 6 64 theme ME 1062:1063 arg1 mycelia 1065:1071 fermented ME mycelia 1052:1071 fermented ME mycelia 1052:1071 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 7 65 theme crude 1216:1220 arg1 lipid 1222:1226 crude lipid 1216:1226 17.17 ± 0.07% crude lipid 1202:1226 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 9 66 theme necropsy 1759:1766 arg1 findings 1768:1775 necropsy findings 1759:1775 necropsy findings 1759:1775 Although there were alterations in hematological and biochemical parameters, organ weights, necropsy findings, and histological markers, they were not considered to be toxicologically significant. 35626955 6 67 theme oral 1035:1038 arg1 toxicity 1040:1047 oral toxicity 1035:1047 oral toxicity of fermented ME mycelia in Sprague Dawley rats 1035:1094 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 7 68 dep U.S. 1384:1387 arg1 recommend 1415:1423 recommend 1415:1423 recommend 1415:1423 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 6 69 theme first 958:962 arg1 time 964:967 the first time 954:967 the first time in this study 954:981 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 7 70 theme 0.07 1210:1213 arg1 ± 1208:1208 ± 1208:1208 ± 1208:1208 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 9 71 theme histological 1782:1793 arg1 markers 1795:1801 histological markers 1782:1801 histological markers 1782:1801 Although there were alterations in hematological and biochemical parameters, organ weights, necropsy findings, and histological markers, they were not considered to be toxicologically significant. 35626955 7 72 theme macronutrients 1362:1375 arg1 proportions 1347:1357 similar proportions 1339:1357 similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend 1339:1423 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 6 73 from time 964:967 arg1 study 977:981 this study 972:981 this study 972:981 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 10 74 used used 2009:2012 arg2 mg/kg/day 1978:1986 greater than 3000 mg/kg/day 1960:1986 greater than 3000 mg/kg/day 1960:1986 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 74 used used 2009:2012 arg2 NOAEL 1935:1939 NOAEL 1935:1939 NOAEL 1935:1939 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 74 used used 2009:2012 arg2 level 1928:1932 the no-observed-adverse-effects level 1896:1932 the no-observed-adverse-effects level (NOAEL) of ME mycelia 1896:1954 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 10 74 used used 2009:2012 arg2 food 2032:2035 a novel food 2024:2035 a novel food at the NOAEL 2024:2048 Hence, the results suggest that the no-observed-adverse-effects level (NOAEL) of ME mycelia was greater than 3000 mg/kg/day and can therefore be used safely as a novel food at the NOAEL. 35626955 5 75 theme high-quality 919:930 arg1 nutrients 932:940 high-quality nutrients 919:940 high-quality nutrients 919:940 However, for M. esculenta mycelia to be used as an innovative food ingredient, it is very important to prove it is safe for human consumption while providing high-quality nutrients. 35626955 4 76 theme large-scale 737:747 arg1 production 749:758 large-scale production 737:758 large-scale production 737:758 For this reason, the cultivation of its mycelia represents a useful alternative for large-scale production. 35626955 5 77 theme M. 774:775 arg1 mycelia 787:793 M. esculenta mycelia to be used as an innovative food ingredient 774:837 M. esculenta mycelia to be used as an innovative food ingredient 774:837 However, for M. esculenta mycelia to be used as an innovative food ingredient, it is very important to prove it is safe for human consumption while providing high-quality nutrients. 35626955 8 78 theme clinical 1607:1614 arg1 ophthalmology 1636:1648 ophthalmology 1636:1648 ophthalmology 1636:1648 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 8 78 theme clinical 1607:1614 arg1 signs 1616:1620 clinical signs 1607:1620 clinical signs 1607:1620 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 8 78 theme clinical 1607:1614 arg1 weight 1628:1633 body weight 1623:1633 body weight 1623:1633 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 8 78 theme clinical 1607:1614 arg1 urinalysis 1655:1664 urinalysis 1655:1664 urinalysis 1655:1664 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 7 79 theme total 1191:1195 arg1 ash 1197:1199 total ash 1191:1199 0.32 ± 0.07% total ash 1178:1199 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 4 80 theme mycelia 693:699 arg1 cultivation 674:684 the cultivation 670:684 the cultivation of its mycelia 670:699 For this reason, the cultivation of its mycelia represents a useful alternative for large-scale production. 35626955 0 81 theme Animal-Tested 22:34 arg1 Safety 36:41 Animal-Tested Safety 22:41 Animal-Tested Safety 22:41 Nutrition Profile and Animal-Tested Safety of Morchella esculenta Mycelia Produced by Fermentation in Bioreactors. 35626955 5 82 theme human 885:889 arg1 consumption 891:901 human consumption 885:901 human consumption 885:901 However, for M. esculenta mycelia to be used as an innovative food ingredient, it is very important to prove it is safe for human consumption while providing high-quality nutrients. 35626955 2 83 theme organic 379:385 arg1 acids 387:391 organic acids 379:391 organic acids 379:391 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 0 84 theme esculenta 56:64 arg1 Mycelia 66:72 Morchella esculenta Mycelia 46:72 Morchella esculenta Mycelia 46:72 Nutrition Profile and Animal-Tested Safety of Morchella esculenta Mycelia Produced by Fermentation in Bioreactors. 35626955 7 85 theme similar 1339:1345 arg1 proportions 1347:1357 similar proportions 1339:1357 similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend 1339:1423 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 7 86 theme 0.49 1162:1165 arg1 ± 1160:1160 ± 1160:1160 ± 1160:1160 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 2 87 theme polyunsaturated 293:307 arg1 acids 315:319 polyunsaturated fatty acids 293:319 polyunsaturated fatty acids 293:319 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 87 theme polyunsaturated 293:307 arg1 polysaccharides 362:376 polysaccharides 362:376 polysaccharides 362:376 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 87 theme polyunsaturated 293:307 arg1 compounds 407:415 polyphenolic compounds 394:415 polyphenolic compounds 394:415 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 87 theme polyunsaturated 293:307 arg1 tocopherols 422:432 tocopherols 422:432 tocopherols 422:432 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 87 theme polyunsaturated 293:307 arg1 acids 387:391 organic acids 379:391 organic acids 379:391 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 8 88 theme ME 1493:1494 arg1 mycelia 1496:1502 ME mycelia 1493:1502 ME mycelia 1493:1502 Moreover, forty male and female Sprague Dawley rats administrating ME mycelia at oral doses of 0, 1000, 2000, and 3000 mg/kg for 90 days showed no significant changes in mortality, clinical signs, body weight, ophthalmology, and urinalysis. 35626955 1 89 theme expensive 188:196 arg1 mushrooms 198:206 the most expensive mushrooms 179:206 the most expensive mushrooms 179:206 Morchella esculenta (ME), or "true" morel mushrooms, are one of the most expensive mushrooms. 35626955 7 90 theme 4.20 1155:1158 arg1 ± 1160:1160 ± 1160:1160 ± 1160:1160 Results showed that the ME mycelia contained 4.20 ± 0.49% moisture, 0.32 ± 0.07% total ash, 17.17 ± 0.07% crude lipid, 39.35 ± 0.35% crude protein, 38.96 ± 4.60% carbohydrates, and 467.77 ± 0.21 kcal/100 g energy, which provides similar proportions of macronutrients as the U.S. Dietary Reference Intakes recommend. 35626955 6 91 from days 1027:1030 arg1 rats 1091:1094 Sprague Dawley rats 1076:1094 Sprague Dawley rats 1076:1094 Hence, for the first time in this study, the nutritional composition, as well as 90 days of oral toxicity of fermented ME mycelia in Sprague Dawley rats, is examined. 35626955 2 92 theme bioactive 334:342 arg1 polysaccharides 362:376 polysaccharides 362:376 polysaccharides 362:376 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 92 theme bioactive 334:342 arg1 acids 387:391 organic acids 379:391 organic acids 379:391 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 92 theme bioactive 334:342 arg1 compounds 407:415 polyphenolic compounds 394:415 polyphenolic compounds 394:415 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 92 theme bioactive 334:342 arg1 tocopherols 422:432 tocopherols 422:432 tocopherols 422:432 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 35626955 2 92 theme bioactive 334:342 arg1 compounds 344:352 several bioactive compounds 326:352 several bioactive compounds 326:352 M. esculenta contain all the important nutrients including carbohydrates, proteins, polyunsaturated fatty acids, and several bioactive compounds such as polysaccharides, organic acids, polyphenolic compounds, and tocopherols, which are promising for antioxidant, immunomodulation, anti-cancer, and anti-inflammatory applications. 36432859 3 0 theme Root 641:644 arg1 growth 646:651 Root growth 641:651 Root growth 641:651 Root growth was inhibited by salinity, whereas the root diameter was thickened in all cultivars. 36432859 8 1 theme significant 1308:1318 arg1 changes 1320:1326 no significant changes 1305:1326 no significant changes in the other two cultivars 1305:1353 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 8 2 theme pectin 1199:1204 arg1 methy-lesterification 1206:1226 pectin methy-lesterification 1199:1226 pectin methy-lesterification of neutral side chains 1199:1249 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 4 3 theme wall 830:833 arg1 viscosity 835:843 cell wall viscosity 825:843 cell wall viscosity in Helan 3 and R7 relative to Prius β 825:881 Salinity significantly reduced cell wall extensibility in all cultivars, and increased cell wall viscosity in Helan 3 and R7 relative to Prius β. 36432859 2 4 theme pectin 427:432 arg1 parameters 586:595 viscosity parameters 576:595 viscosity parameters 576:595 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 4 theme pectin 427:432 arg1 ratio 501:505 the HG:RG-I ratio 489:505 the HG:RG-I ratio 489:505 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 4 theme pectin 427:432 arg1 polysaccharides 387:401 the pectin polysaccharides 376:401 the pectin polysaccharides 376:401 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 4 theme pectin 427:432 arg1 elasticity 561:570 elasticity 561:570 elasticity 561:570 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 4 theme pectin 427:432 arg1 characteristics 408:422 the characteristics 404:422 the characteristics 404:422 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 4 theme pectin 427:432 arg1 chains 521:526 neutral side chains 508:526 neutral side chains (galactan/arabinangalactan) 508:554 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 4 theme pectin 427:432 arg1 degree 449:454 the degree 445:454 the degree of pectin methy-lesterification 445:486 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 10 5 theme important 1505:1513 arg1 roles 1515:1519 important roles 1505:1519 important roles 1505:1519 In this study, it is shown that cell wall pectin played important roles in regulating the root growth of Spinacia oleracea L. under salinity stress. 36432859 1 6 theme physical 227:234 arg1 properties 236:245 physical properties 227:245 physical properties 227:245 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 2 7 theme methy-lesterification 466:486 arg1 ratio 501:505 the HG:RG-I ratio 489:505 the HG:RG-I ratio 489:505 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 7 theme methy-lesterification 466:486 arg1 galactan/arabinangalactan 529:553 galactan/arabinangalactan 529:553 galactan/arabinangalactan 529:553 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 7 theme methy-lesterification 466:486 arg1 chains 521:526 neutral side chains 508:526 neutral side chains (galactan/arabinangalactan) 508:554 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 7 theme methy-lesterification 466:486 arg1 degree 449:454 the degree 445:454 the degree of pectin methy-lesterification 445:486 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 7 theme methy-lesterification 466:486 arg1 elasticity 561:570 elasticity 561:570 elasticity 561:570 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 9 8 theme salt 1414:1417 arg1 tolerance 1419:1427 salt tolerance 1414:1427 salt tolerance in the R7 cultivar 1414:1446 Demethylation of pectin could alter root growth and boost salt tolerance in the R7 cultivar. 36432859 9 9 from tolerance 1419:1427 arg1 cultivar 1439:1446 the R7 cultivar 1432:1446 the R7 cultivar 1432:1446 Demethylation of pectin could alter root growth and boost salt tolerance in the R7 cultivar. 36432859 2 10 theme pectin 459:464 arg1 methy-lesterification 466:486 pectin methy-lesterification 459:486 pectin methy-lesterification 459:486 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 11 theme side 516:519 arg1 galactan/arabinangalactan 529:553 galactan/arabinangalactan 529:553 galactan/arabinangalactan 529:553 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 11 theme side 516:519 arg1 chains 521:526 neutral side chains 508:526 neutral side chains (galactan/arabinangalactan) 508:554 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 12 theme viscosity 576:584 arg1 parameters 586:595 viscosity parameters 576:595 viscosity parameters 576:595 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 12 theme viscosity 576:584 arg1 ratio 501:505 the HG:RG-I ratio 489:505 the HG:RG-I ratio 489:505 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 12 theme viscosity 576:584 arg1 polysaccharides 387:401 the pectin polysaccharides 376:401 the pectin polysaccharides 376:401 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 12 theme viscosity 576:584 arg1 elasticity 561:570 elasticity 561:570 elasticity 561:570 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 12 theme viscosity 576:584 arg1 chains 521:526 neutral side chains 508:526 neutral side chains (galactan/arabinangalactan) 508:554 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 12 theme viscosity 576:584 arg1 degree 449:454 the degree 445:454 the degree of pectin methy-lesterification 445:486 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 8 13 theme methy-lesterification 1206:1226 arg1 degree 1189:1194 degree 1189:1194 degree 1189:1194 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 8 13 theme methy-lesterification 1206:1226 arg1 length 1178:1183 length 1178:1183 length 1178:1183 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 10 14 theme Spinacia 1554:1561 arg1 growth 1544:1549 the root growth 1535:1549 the root growth of Spinacia 1535:1561 In this study, it is shown that cell wall pectin played important roles in regulating the root growth of Spinacia oleracea L. under salinity stress. 36432859 2 15 dep salt-sensitive 269:282 arg1 Prius 297:301 Prius 297:301 Prius 297:301 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 15 dep salt-sensitive 269:282 arg1 cultivars 341:349 spinach cultivars 333:349 spinach cultivars 333:349 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 15 dep salt-sensitive 269:282 arg1 Helan 285:289 Helan 285:289 Helan 285:289 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 8 16 theme side 1239:1242 arg1 chains 1244:1249 neutral side chains 1231:1249 neutral side chains 1231:1249 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 2 17 theme spinach 333:339 arg1 cultivars 341:349 spinach cultivars 333:349 spinach cultivars 333:349 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 4 18 theme Prius 875:879 arg1 β 881:881 Prius β 875:881 Prius β 875:881 Salinity significantly reduced cell wall extensibility in all cultivars, and increased cell wall viscosity in Helan 3 and R7 relative to Prius β. 36432859 4 19 from extensibility 779:791 arg1 cultivars 800:808 all cultivars 796:808 all cultivars 796:808 Salinity significantly reduced cell wall extensibility in all cultivars, and increased cell wall viscosity in Helan 3 and R7 relative to Prius β. 36432859 4 20 theme wall 774:777 arg1 extensibility 779:791 cell wall extensibility 769:791 cell wall extensibility in all cultivars 769:808 Salinity significantly reduced cell wall extensibility in all cultivars, and increased cell wall viscosity in Helan 3 and R7 relative to Prius β. 36432859 0 21 theme Pectin 0:5 arg1 Characteristics 7:21 Pectin Characteristics 0:21 Pectin Characteristics 0:21 Pectin Characteristics Affect Root Growth in Spinach under Salinity. 36432859 6 22 dep HG 1059:1060 arg1 ratio 1067:1071 RG-I ratio 1062:1071 HG:RG-I ratio 1059:1071 Cell wall viscosity was affected by pectin due to the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio). 36432859 0 23 from Growth 35:40 arg1 Spinach 45:51 Spinach 45:51 Spinach 45:51 Pectin Characteristics Affect Root Growth in Spinach under Salinity. 36432859 2 24 theme elongation 609:618 arg1 zone 620:623 the root elongation zone 600:623 the root elongation zone under salinity 600:638 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 9 25 theme R7 1436:1437 arg1 cultivar 1439:1446 the R7 cultivar 1432:1446 the R7 cultivar 1432:1446 Demethylation of pectin could alter root growth and boost salt tolerance in the R7 cultivar. 36432859 9 26 theme pectin 1373:1378 arg1 Demethylation 1356:1368 Demethylation 1356:1368 Demethylation of pectin 1356:1378 Demethylation of pectin could alter root growth and boost salt tolerance in the R7 cultivar. 36432859 2 27 theme pectin 380:385 arg1 parameters 586:595 viscosity parameters 576:595 viscosity parameters 576:595 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 27 theme pectin 380:385 arg1 ratio 501:505 the HG:RG-I ratio 489:505 the HG:RG-I ratio 489:505 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 27 theme pectin 380:385 arg1 polysaccharides 387:401 the pectin polysaccharides 376:401 the pectin polysaccharides 376:401 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 27 theme pectin 380:385 arg1 elasticity 561:570 elasticity 561:570 elasticity 561:570 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 27 theme pectin 380:385 arg1 characteristics 408:422 the characteristics 404:422 the characteristics 404:422 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 27 theme pectin 380:385 arg1 chains 521:526 neutral side chains 508:526 neutral side chains (galactan/arabinangalactan) 508:554 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 27 theme pectin 380:385 arg1 degree 449:454 the degree 445:454 the degree of pectin methy-lesterification 445:486 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 28 theme root 604:607 arg1 zone 620:623 the root elongation zone 600:623 the root elongation zone under salinity 600:638 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 6 29 theme RG-I 1062:1065 arg1 ratio 1067:1071 RG-I ratio 1062:1071 HG:RG-I ratio 1059:1071 Cell wall viscosity was affected by pectin due to the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio). 36432859 10 30 theme wall 1486:1489 arg1 pectin 1491:1496 cell wall pectin 1481:1496 cell wall pectin 1481:1496 In this study, it is shown that cell wall pectin played important roles in regulating the root growth of Spinacia oleracea L. under salinity stress. 36432859 0 31 theme Root 30:33 arg1 Growth 35:40 Root Growth 30:40 Root Growth in Spinach 30:51 Pectin Characteristics Affect Root Growth in Spinach under Salinity. 36432859 1 32 theme cell 254:257 arg1 wall 259:262 the cell wall 250:262 the cell wall 250:262 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 8 33 from changes 1320:1326 arg1 cultivars 1345:1353 the other two cultivars 1331:1353 the other two cultivars 1331:1353 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 8 34 theme chains 1244:1249 arg1 methy-lesterification 1206:1226 pectin methy-lesterification 1199:1226 pectin methy-lesterification of neutral side chains 1199:1249 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 1 35 theme wall 259:262 arg1 composition 211:221 pectin composition 204:221 pectin composition 204:221 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 1 35 theme wall 259:262 arg1 properties 236:245 physical properties 227:245 physical properties 227:245 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 2 36 theme HG 493:494 arg1 ratio 501:505 the HG:RG-I ratio 489:505 the HG:RG-I ratio 489:505 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 7 37 from proportion 1085:1094 arg1 pectin 1114:1119 pectin 1114:1119 pectin 1114:1119 The molar proportion of uronic acid in pectin was reduced in Helan 3 and R7 compared with Prius β. 36432859 1 38 theme root 98:101 arg1 mechanisms 113:122 root cell wall mechanisms 98:122 root cell wall mechanisms 98:122 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 6 39 theme acid 1023:1026 arg1 proportion 1002:1011 the molar proportion 992:1011 the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio) 992:1072 Cell wall viscosity was affected by pectin due to the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio). 36432859 8 40 theme neutral 1231:1237 arg1 chains 1244:1249 neutral side chains 1231:1249 neutral side chains 1231:1249 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 6 41 theme characteristics 1042:1056 arg1 proportion 1002:1011 the molar proportion 992:1011 the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio) 992:1072 Cell wall viscosity was affected by pectin due to the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio). 36432859 1 42 dep composition 211:221 arg1 the 200:202 the 200:202 the 200:202 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 6 43 theme molar 996:1000 arg1 proportion 1002:1011 the molar proportion 992:1011 the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio) 992:1072 Cell wall viscosity was affected by pectin due to the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio). 36432859 8 44 theme other 1335:1339 arg1 cultivars 1345:1353 the other two cultivars 1331:1353 the other two cultivars 1331:1353 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 6 45 theme Cell 942:945 arg1 viscosity 952:960 Cell wall viscosity 942:960 Cell wall viscosity 942:960 Cell wall viscosity was affected by pectin due to the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio). 36432859 7 46 theme uronic 1099:1104 arg1 acid 1106:1109 uronic acid 1099:1109 uronic acid 1099:1109 The molar proportion of uronic acid in pectin was reduced in Helan 3 and R7 compared with Prius β. 36432859 2 47 theme neutral 508:514 arg1 galactan/arabinangalactan 529:553 galactan/arabinangalactan 529:553 galactan/arabinangalactan 529:553 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 47 theme neutral 508:514 arg1 chains 521:526 neutral side chains 508:526 neutral side chains (galactan/arabinangalactan) 508:554 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 7 48 theme acid 1106:1109 arg1 proportion 1085:1094 The molar proportion 1075:1094 The molar proportion of uronic acid in pectin 1075:1119 The molar proportion of uronic acid in pectin was reduced in Helan 3 and R7 compared with Prius β. 36432859 4 49 theme cell 769:772 arg1 extensibility 779:791 cell wall extensibility 769:791 cell wall extensibility in all cultivars 769:808 Salinity significantly reduced cell wall extensibility in all cultivars, and increased cell wall viscosity in Helan 3 and R7 relative to Prius β. 36432859 1 50 from changes 189:195 arg1 composition 211:221 pectin composition 204:221 pectin composition 204:221 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 1 50 from changes 189:195 arg1 properties 236:245 physical properties 227:245 physical properties 227:245 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 1 51 theme cell 103:106 arg1 mechanisms 113:122 root cell wall mechanisms 98:122 root cell wall mechanisms 98:122 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 3 52 theme root 692:695 arg1 diameter 697:704 the root diameter 688:704 the root diameter 688:704 Root growth was inhibited by salinity, whereas the root diameter was thickened in all cultivars. 36432859 4 53 theme cell 825:828 arg1 viscosity 835:843 cell wall viscosity 825:843 cell wall viscosity in Helan 3 and R7 relative to Prius β 825:881 Salinity significantly reduced cell wall extensibility in all cultivars, and increased cell wall viscosity in Helan 3 and R7 relative to Prius β. 36432859 8 54 theme R7 1287:1288 arg1 cultivar 1290:1297 the R7 cultivar 1283:1297 the R7 cultivar 1283:1297 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 2 55 used used 356:359 arg2 salt-tolerant 314:326 salt-tolerant 314:326 salt-tolerant 314:326 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 55 used used 356:359 arg2 salt-sensitive 269:282 salt-sensitive 269:282 salt-sensitive 269:282 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 2 55 used used 356:359 arg2 R7 329:330 R7 329:330 R7 329:330 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 1 56 theme wall 108:111 arg1 mechanisms 113:122 root cell wall mechanisms 98:122 root cell wall mechanisms 98:122 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 10 57 theme cell 1481:1484 arg1 pectin 1491:1496 cell wall pectin 1481:1496 cell wall pectin 1481:1496 In this study, it is shown that cell wall pectin played important roles in regulating the root growth of Spinacia oleracea L. under salinity stress. 36432859 4 58 from viscosity 835:843 arg1 Helan 848:852 Helan 848:852 Helan 848:852 Salinity significantly reduced cell wall extensibility in all cultivars, and increased cell wall viscosity in Helan 3 and R7 relative to Prius β. 36432859 4 58 from viscosity 835:843 arg1 R7 860:861 R7 860:861 R7 860:861 Salinity significantly reduced cell wall extensibility in all cultivars, and increased cell wall viscosity in Helan 3 and R7 relative to Prius β. 36432859 8 59 dep length 1178:1183 arg1 The 1174:1176 The 1174:1176 The 1174:1176 The length and degree of pectin methy-lesterification of neutral side chains were significantly decreased in the R7 cultivar, with no significant changes in the other two cultivars. 36432859 6 60 theme wall 947:950 arg1 viscosity 952:960 Cell wall viscosity 942:960 Cell wall viscosity 942:960 Cell wall viscosity was affected by pectin due to the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio). 36432859 1 61 theme mechanisms 113:122 arg1 role 90:93 the role 86:93 the role of root cell wall mechanisms in plant tolerance to salinity 86:153 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 10 62 theme salinity 1581:1588 arg1 stress 1590:1595 salinity stress 1581:1595 salinity stress 1581:1595 In this study, it is shown that cell wall pectin played important roles in regulating the root growth of Spinacia oleracea L. under salinity stress. 36432859 2 63 theme RG-I 496:499 arg1 ratio 501:505 the HG:RG-I ratio 489:505 the HG:RG-I ratio 489:505 Two salt-sensitive (Helan 3 and Prius β) and one salt-tolerant (R7) spinach cultivars were used to investigate the pectin polysaccharides, the characteristics of pectin, including the degree of pectin methy-lesterification, the HG:RG-I ratio, neutral side chains (galactan/arabinangalactan), and elasticity and viscosity parameters in the root elongation zone under salinity. 36432859 10 64 theme root 1539:1542 arg1 growth 1544:1549 the root growth 1535:1549 the root growth of Spinacia 1535:1561 In this study, it is shown that cell wall pectin played important roles in regulating the root growth of Spinacia oleracea L. under salinity stress. 36432859 6 65 theme pectin 1035:1040 arg1 characteristics 1042:1056 pectin characteristics 1035:1056 pectin characteristics 1035:1056 Cell wall viscosity was affected by pectin due to the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio). 36432859 5 66 theme salinity 925:932 arg1 stress 934:939 salinity stress 925:939 salinity stress 925:939 Pectin was significantly increased under salinity stress. 36432859 9 67 theme root 1392:1395 arg1 growth 1397:1402 root growth 1392:1402 root growth 1392:1402 Demethylation of pectin could alter root growth and boost salt tolerance in the R7 cultivar. 36432859 1 68 theme plant 127:131 arg1 tolerance 133:141 plant tolerance 127:141 plant tolerance to salinity 127:153 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 1 69 from role 90:93 arg1 tolerance 133:141 plant tolerance 127:141 plant tolerance to salinity 127:153 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 1 70 theme pectin 204:209 arg1 composition 211:221 pectin composition 204:221 pectin composition 204:221 In understanding the role of root cell wall mechanisms in plant tolerance to salinity, it is important to elucidate the changes in the pectin composition and physical properties of the cell wall. 36432859 7 71 theme Prius 1165:1169 arg1 β 1171:1171 Prius β 1165:1171 Prius β 1165:1171 The molar proportion of uronic acid in pectin was reduced in Helan 3 and R7 compared with Prius β. 36432859 6 72 theme uronic 1016:1021 arg1 HG 1059:1060 HG 1059:1060 HG:RG-I ratio 1059:1071 Cell wall viscosity was affected by pectin due to the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio). 36432859 6 72 theme uronic 1016:1021 arg1 acid 1023:1026 uronic acid 1016:1026 uronic acid 1016:1026 Cell wall viscosity was affected by pectin due to the molar proportion of uronic acid and/or pectin characteristics (HG:RG-I ratio). 36432859 7 73 theme molar 1079:1083 arg1 proportion 1085:1094 The molar proportion 1075:1094 The molar proportion of uronic acid in pectin 1075:1119 The molar proportion of uronic acid in pectin was reduced in Helan 3 and R7 compared with Prius β. 36432859 4 74 theme relative 863:870 arg1 viscosity 835:843 cell wall viscosity 825:843 cell wall viscosity in Helan 3 and R7 relative to Prius β 825:881 Salinity significantly reduced cell wall extensibility in all cultivars, and increased cell wall viscosity in Helan 3 and R7 relative to Prius β. 35873450 12 0 theme mn 2278:2279 arg1 mm 2282:2283 the mn, mm, and ma groups 2274:2298 mm 2282:2283 In the LEfSe analysis, there were significant differences in the characteristic bacteria in the mn, mm, and ma groups. 35873450 8 1 theme Shannon 1507:1513 arg1 index 1515:1519 the Shannon index 1503:1519 the Shannon index 1503:1519 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 8 1 theme Shannon 1507:1513 arg1 smallest 1529:1536 the smallest 1525:1536 the smallest in the mm group 1525:1552 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 8 1 theme Shannon 1507:1513 arg1 index 1477:1481 the Simpson index 1465:1481 the Simpson index was the largest 1465:1497 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 3 2 theme scientific 692:701 arg1 basis 703:707 the scientific basis 688:707 the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea 688:766 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 2 3 theme intestinal 365:374 arg1 bacteria 376:383 beneficial intestinal bacteria 354:383 beneficial intestinal bacteria 354:383 Previous research has reported that plant polysaccharides can promote the growth of beneficial intestinal bacteria and inhibit the multiplication of pathogenic bacteria, thus effectively treating diarrhea. 35873450 13 4 theme further 2466:2472 arg1 investigation 2474:2486 further investigation 2466:2486 further investigation 2466:2486 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 10 5 theme ma 1880:1881 arg1 groups 1883:1888 the mn and ma groups 1869:1888 groups 1883:1888 In contrast, the samples in the mm group were more scattered and farther away from the samples in the mn and ma groups, i.e., the community structure similarity within and between the groups was low. 35873450 3 6 theme QWBZP 729:733 arg1 polysaccharide 741:754 QWBZP crude polysaccharide 729:754 QWBZP crude polysaccharide on diarrhea 729:766 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 3 7 theme bacteria 578:585 arg1 diversity 546:554 the diversity 542:554 the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD 542:644 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 13 8 theme QWBZP 2425:2429 arg1 polysaccharide 2437:2450 the QWBZP crude polysaccharide 2421:2450 the QWBZP crude polysaccharide 2421:2450 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 10 9 theme community 1901:1909 arg1 similarity 1921:1930 the community structure similarity 1897:1930 the community structure similarity within and between the groups was low 1897:1968 In contrast, the samples in the mm group were more scattered and farther away from the samples in the mn and ma groups, i.e., the community structure similarity within and between the groups was low. 35873450 3 10 from effect 502:507 arg1 diversity 546:554 the diversity 542:554 the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD 542:644 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 3 11 theme intestinal 559:568 arg1 bacteria 578:585 intestinal mucosal bacteria 559:585 intestinal mucosal bacteria 559:585 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 8 12 theme significant 1572:1582 arg1 difference 1584:1593 no significant difference 1569:1593 no significant difference 1569:1593 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 7 13 theme mice 1364:1367 arg1 mice 1364:1367 mice 1364:1367 mice 1364:1367 Results The spleen and thymus indices of each group of mice had no significant differences. 35873450 7 13 theme mice 1364:1367 arg1 group 1355:1359 each group 1350:1359 each group of mice 1350:1367 Results The spleen and thymus indices of each group of mice had no significant differences. 35873450 13 14 dep Conclusion 2301:2310 arg1 component 2344:2352 The single crude polysaccharide component 2312:2352 The single crude polysaccharide component 2312:2352 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 13 14 dep Conclusion 2301:2310 arg1 effective 2366:2374 effective 2366:2374 effective 2366:2374 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 9 15 theme community 1750:1758 arg1 structure 1760:1768 community structure 1750:1768 community structure 1750:1768 In the PCA and PCoA, the mn and ma group samples were both relatively concentrated with a high similarity of community structure. 35873450 3 16 theme structure 607:615 arg1 composition 617:627 their community structure composition 591:627 their community structure composition 591:627 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 13 17 theme clinical 2400:2407 arg1 subject 2455:2461 subject 2455:2461 subject 2455:2461 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 13 17 theme clinical 2400:2407 arg1 efficacy 2409:2416 the clinical efficacy 2396:2416 the clinical efficacy of the QWBZP crude polysaccharide 2396:2450 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 7 18 dep Results 1309:1315 arg1 had 1369:1371 had 1369:1371 had no significant differences 1369:1398 Results The spleen and thymus indices of each group of mice had no significant differences. 35873450 11 19 theme F/B 2090:2092 arg1 ratio 2095:2099 the Firmicutes/Bacteroidetes (F/B) ratio 2060:2099 the Firmicutes/Bacteroidetes (F/B) ratio 2060:2099 Compared with the mm group, the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group was decreased, while that of Enterococcus continued to increase. 35873450 3 20 theme polysaccharide 741:754 arg1 efficacy 717:724 the efficacy 713:724 the efficacy of QWBZP crude polysaccharide on diarrhea 713:766 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 0 21 theme Mucosal 133:139 arg1 Bacteria 141:148 Intestinal Mucosal Bacteria 122:148 Intestinal Mucosal Bacteria 122:148 The Effect of Qiweibaizhu Powder Crude Polysaccharide on Antibiotic-Associated Diarrhea Mice Is Associated With Restoring Intestinal Mucosal Bacteria. 35873450 2 22 theme plant 306:310 arg1 polysaccharides 312:326 plant polysaccharides 306:326 plant polysaccharides 306:326 Previous research has reported that plant polysaccharides can promote the growth of beneficial intestinal bacteria and inhibit the multiplication of pathogenic bacteria, thus effectively treating diarrhea. 35873450 8 23 theme diversity 1602:1610 arg1 indices 1612:1618 the diversity indices 1598:1618 the diversity indices of all three groups 1598:1638 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 11 24 theme Firmicutes/Bacteroidetes 2064:2087 arg1 ratio 2095:2099 the Firmicutes/Bacteroidetes (F/B) ratio 2060:2099 the Firmicutes/Bacteroidetes (F/B) ratio 2060:2099 Compared with the mm group, the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group was decreased, while that of Enterococcus continued to increase. 35873450 6 25 theme MiSeq 1235:1239 arg1 sequencing 1241:1250 MiSeq sequencing 1235:1250 MiSeq sequencing 1235:1250 The intestinal mucosa was extracted from the jejunum to the ileum of mice, and the metagenome was extracted and then analyzed using MiSeq sequencing to characterize the intestinal mucosal bacteria in mice. 35873450 4 26 theme model 872:876 arg1 group 883:887 the model (mm) group 868:887 the model (mm) group 868:887 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 4 26 theme model 872:876 arg1 mm 879:880 mm 879:880 mm 879:880 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 10 27 theme mm 1803:1804 arg1 group 1806:1810 the mm group 1799:1810 the mm group 1799:1810 In contrast, the samples in the mm group were more scattered and farther away from the samples in the mn and ma groups, i.e., the community structure similarity within and between the groups was low. 35873450 5 28 theme AAD 979:981 arg1 model 983:987 An AAD model 976:987 An AAD model 976:987 An AAD model was constructed using a mixed antibiotic solution and treated with gavage crude polysaccharide solution of QWBZP. 35873450 7 29 contain had 1369:1371 arg2 differences 1388:1398 no significant differences 1373:1398 no significant differences 1373:1398 Results The spleen and thymus indices of each group of mice had no significant differences. 35873450 7 29 contain had 1369:1371 arg1 indices 1339:1345 The spleen and thymus indices 1317:1345 The spleen and thymus indices of each group of mice 1317:1367 Results The spleen and thymus indices of each group of mice had no significant differences. 35873450 0 30 theme Antibiotic-Associated 57:77 arg1 Mice 88:91 Antibiotic-Associated Diarrhea Mice 57:91 Antibiotic-Associated Diarrhea Mice 57:91 The Effect of Qiweibaizhu Powder Crude Polysaccharide on Antibiotic-Associated Diarrhea Mice Is Associated With Restoring Intestinal Mucosal Bacteria. 35873450 11 31 theme mm 1989:1990 arg1 group 1992:1996 the mm group 1985:1996 the mm group 1985:1996 Compared with the mm group, the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group was decreased, while that of Enterococcus continued to increase. 35873450 8 32 theme Chao1 1405:1409 arg1 similar 1456:1462 similar 1456:1462 similar 1456:1462 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 8 32 theme Chao1 1405:1409 arg1 indices 1419:1425 The Chao1 and ACE indices 1401:1425 indices 1419:1425 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 5 33 theme gavage 1056:1061 arg1 solution 1084:1091 gavage crude polysaccharide solution 1056:1091 gavage crude polysaccharide solution of QWBZP 1056:1100 An AAD model was constructed using a mixed antibiotic solution and treated with gavage crude polysaccharide solution of QWBZP. 35873450 4 34 dep Materials 769:777 arg1 mice 813:816 Eighteen Kunming (KM) mice 791:816 Eighteen Kunming (KM) mice 791:816 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 4 35 theme QWBZP 898:902 arg1 group 940:944 the QWBZP crude polysaccharide treatment (ma) group 894:944 the QWBZP crude polysaccharide treatment (ma) group 894:944 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 8 36 theme ACE 1415:1417 arg1 similar 1456:1462 similar 1456:1462 similar 1456:1462 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 8 36 theme ACE 1415:1417 arg1 indices 1419:1425 The Chao1 and ACE indices 1401:1425 indices 1419:1425 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 6 37 theme mucosal 1283:1289 arg1 bacteria 1291:1298 the intestinal mucosal bacteria 1268:1298 the intestinal mucosal bacteria in mice 1268:1306 The intestinal mucosa was extracted from the jejunum to the ileum of mice, and the metagenome was extracted and then analyzed using MiSeq sequencing to characterize the intestinal mucosal bacteria in mice. 35873450 5 38 theme mixed 1013:1017 arg1 solution 1030:1037 a mixed antibiotic solution 1011:1037 a mixed antibiotic solution 1011:1037 An AAD model was constructed using a mixed antibiotic solution and treated with gavage crude polysaccharide solution of QWBZP. 35873450 6 39 theme intestinal 1107:1116 arg1 mucosa 1118:1123 The intestinal mucosa 1103:1123 The intestinal mucosa 1103:1123 The intestinal mucosa was extracted from the jejunum to the ileum of mice, and the metagenome was extracted and then analyzed using MiSeq sequencing to characterize the intestinal mucosal bacteria in mice. 35873450 1 40 theme Background 151:160 arg1 powder 174:179 Background Qiweibaizhu powder 151:179 Background Qiweibaizhu powder (QWBZP) 151:187 Background Qiweibaizhu powder (QWBZP) has been shown to be effective in treating antibiotic-associated diarrhea (AAD). 35873450 1 40 theme Background 151:160 arg1 QWBZP 182:186 QWBZP 182:186 QWBZP 182:186 Background Qiweibaizhu powder (QWBZP) has been shown to be effective in treating antibiotic-associated diarrhea (AAD). 35873450 4 41 theme polysaccharide 910:923 arg1 group 940:944 the QWBZP crude polysaccharide treatment (ma) group 894:944 the QWBZP crude polysaccharide treatment (ma) group 894:944 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 10 42 theme structure 1911:1919 arg1 similarity 1921:1930 the community structure similarity 1897:1930 the community structure similarity within and between the groups was low 1897:1968 In contrast, the samples in the mm group were more scattered and farther away from the samples in the mn and ma groups, i.e., the community structure similarity within and between the groups was low. 35873450 3 43 from polysaccharide 741:754 arg1 diarrhea 759:766 diarrhea 759:766 diarrhea 759:766 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 8 44 from smallest 1529:1536 arg1 group 1548:1552 the mm group 1541:1552 the mm group 1541:1552 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 2 45 theme pathogenic 419:428 arg1 bacteria 430:437 pathogenic bacteria 419:437 pathogenic bacteria 419:437 Previous research has reported that plant polysaccharides can promote the growth of beneficial intestinal bacteria and inhibit the multiplication of pathogenic bacteria, thus effectively treating diarrhea. 35873450 6 46 from bacteria 1291:1298 arg1 mice 1303:1306 mice 1303:1306 mice 1303:1306 The intestinal mucosa was extracted from the jejunum to the ileum of mice, and the metagenome was extracted and then analyzed using MiSeq sequencing to characterize the intestinal mucosal bacteria in mice. 35873450 8 47 theme mn 1434:1435 arg1 groups 1444:1449 the mn and mm groups 1430:1449 groups 1444:1449 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 3 48 from diarrhea 759:766 arg1 efficacy 717:724 the efficacy 713:724 the efficacy of QWBZP crude polysaccharide on diarrhea 713:766 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 11 49 from abundance 2012:2020 arg1 group 2111:2115 the ma group 2104:2115 the ma group 2104:2115 Compared with the mm group, the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group was decreased, while that of Enterococcus continued to increase. 35873450 8 50 theme mm 1441:1442 arg1 groups 1444:1449 the mn and mm groups 1430:1449 groups 1444:1449 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 12 51 theme characteristic 2247:2260 arg1 bacteria 2262:2269 the characteristic bacteria 2243:2269 the characteristic bacteria 2243:2269 In the LEfSe analysis, there were significant differences in the characteristic bacteria in the mn, mm, and ma groups. 35873450 3 52 theme study 667:671 arg1 aim 655:657 the aim 651:657 the aim of this study 651:671 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 0 53 theme Powder 26:31 arg1 Polysaccharide 39:52 Qiweibaizhu Powder Crude Polysaccharide 14:52 Qiweibaizhu Powder Crude Polysaccharide 14:52 The Effect of Qiweibaizhu Powder Crude Polysaccharide on Antibiotic-Associated Diarrhea Mice Is Associated With Restoring Intestinal Mucosal Bacteria. 35873450 5 54 theme polysaccharide 1069:1082 arg1 solution 1084:1091 gavage crude polysaccharide solution 1056:1091 gavage crude polysaccharide solution of QWBZP 1056:1100 An AAD model was constructed using a mixed antibiotic solution and treated with gavage crude polysaccharide solution of QWBZP. 35873450 2 55 theme beneficial 354:363 arg1 bacteria 376:383 beneficial intestinal bacteria 354:383 beneficial intestinal bacteria 354:383 Previous research has reported that plant polysaccharides can promote the growth of beneficial intestinal bacteria and inhibit the multiplication of pathogenic bacteria, thus effectively treating diarrhea. 35873450 3 56 theme QWBZP 512:516 arg1 polysaccharide 524:537 QWBZP crude polysaccharide 512:537 QWBZP crude polysaccharide 512:537 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 0 57 theme Polysaccharide 39:52 arg1 Effect 4:9 The Effect 0:9 The Effect of Qiweibaizhu Powder Crude Polysaccharide on Antibiotic-Associated Diarrhea Mice 0:91 The Effect of Qiweibaizhu Powder Crude Polysaccharide on Antibiotic-Associated Diarrhea Mice Is Associated With Restoring Intestinal Mucosal Bacteria. 35873450 9 58 theme group 1676:1680 arg1 samples 1682:1688 the mn and ma group samples 1662:1688 samples 1682:1688 In the PCA and PCoA, the mn and ma group samples were both relatively concentrated with a high similarity of community structure. 35873450 8 59 theme Simpson 1469:1475 arg1 index 1515:1519 the Shannon index 1503:1519 the Shannon index 1503:1519 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 8 59 theme Simpson 1469:1475 arg1 smallest 1529:1536 the smallest 1525:1536 the smallest in the mm group 1525:1552 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 8 59 theme Simpson 1469:1475 arg1 index 1477:1481 the Simpson index 1465:1481 the Simpson index was the largest 1465:1497 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 13 60 theme polysaccharide 2437:2450 arg1 subject 2455:2461 subject 2455:2461 subject 2455:2461 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 13 60 theme polysaccharide 2437:2450 arg1 efficacy 2409:2416 the clinical efficacy 2396:2416 the clinical efficacy of the QWBZP crude polysaccharide 2396:2450 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 3 61 with mice 632:635 arg1 AAD 642:644 AAD 642:644 AAD 642:644 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 2 62 theme bacteria 376:383 arg1 growth 344:349 the growth 340:349 the growth of beneficial intestinal bacteria 340:383 Previous research has reported that plant polysaccharides can promote the growth of beneficial intestinal bacteria and inhibit the multiplication of pathogenic bacteria, thus effectively treating diarrhea. 35873450 8 63 theme mm 1545:1546 arg1 group 1548:1552 the mm group 1541:1552 the mm group 1541:1552 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 7 64 theme significant 1376:1386 arg1 differences 1388:1398 no significant differences 1373:1398 no significant differences 1373:1398 Results The spleen and thymus indices of each group of mice had no significant differences. 35873450 11 65 theme ma 2108:2109 arg1 group 2111:2115 the ma group 2104:2115 the ma group 2104:2115 Compared with the mm group, the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group was decreased, while that of Enterococcus continued to increase. 35873450 3 66 theme mucosal 570:576 arg1 bacteria 578:585 intestinal mucosal bacteria 559:585 intestinal mucosal bacteria 559:585 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 7 67 theme group 1355:1359 arg1 indices 1339:1345 The spleen and thymus indices 1317:1345 The spleen and thymus indices of each group of mice 1317:1367 Results The spleen and thymus indices of each group of mice had no significant differences. 35873450 9 68 theme high 1731:1734 arg1 similarity 1736:1745 a high similarity 1729:1745 a high similarity of community structure 1729:1768 In the PCA and PCoA, the mn and ma group samples were both relatively concentrated with a high similarity of community structure. 35873450 11 69 theme Lactobacillus 2041:2053 arg1 abundance 2012:2020 the relative abundance 1999:2020 the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group 1999:2115 Compared with the mm group, the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group was decreased, while that of Enterococcus continued to increase. 35873450 3 70 theme crude 735:739 arg1 polysaccharide 741:754 QWBZP crude polysaccharide 729:754 QWBZP crude polysaccharide on diarrhea 729:766 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 3 71 from diversity 546:554 arg1 mice 632:635 mice 632:635 mice with AAD 632:644 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 13 72 theme crude 2431:2435 arg1 polysaccharide 2437:2450 the QWBZP crude polysaccharide 2421:2450 the QWBZP crude polysaccharide 2421:2450 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 13 73 theme crude 2323:2327 arg1 component 2344:2352 The single crude polysaccharide component 2312:2352 The single crude polysaccharide component 2312:2352 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 13 73 theme crude 2323:2327 arg1 effective 2366:2374 effective 2366:2374 effective 2366:2374 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 3 74 from efficacy 717:724 arg1 diarrhea 759:766 diarrhea 759:766 diarrhea 759:766 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 6 75 theme mice 1172:1175 arg1 ileum 1163:1167 the ileum 1159:1167 the ileum of mice 1159:1175 The intestinal mucosa was extracted from the jejunum to the ileum of mice, and the metagenome was extracted and then analyzed using MiSeq sequencing to characterize the intestinal mucosal bacteria in mice. 35873450 3 76 theme community 597:605 arg1 composition 617:627 their community structure composition 591:627 their community structure composition 591:627 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 4 77 theme normal 849:854 arg1 group 861:865 the normal (mn) group 845:865 the normal (mn) group 845:865 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 4 77 theme normal 849:854 arg1 mn 857:858 mn 857:858 mn 857:858 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 7 78 theme thymus 1332:1337 arg1 indices 1339:1345 The spleen and thymus indices 1317:1345 The spleen and thymus indices of each group of mice 1317:1367 Results The spleen and thymus indices of each group of mice had no significant differences. 35873450 9 79 theme structure 1760:1768 arg1 similarity 1736:1745 a high similarity 1729:1745 a high similarity of community structure 1729:1768 In the PCA and PCoA, the mn and ma group samples were both relatively concentrated with a high similarity of community structure. 35873450 7 80 theme spleen 1321:1326 arg1 indices 1339:1345 The spleen and thymus indices 1317:1345 The spleen and thymus indices of each group of mice 1317:1367 Results The spleen and thymus indices of each group of mice had no significant differences. 35873450 3 81 theme polysaccharide 524:537 arg1 effect 502:507 the effect 498:507 the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD 498:644 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 12 82 theme ma 2290:2291 arg1 groups 2293:2298 the mn, mm, and ma groups 2274:2298 groups 2293:2298 In the LEfSe analysis, there were significant differences in the characteristic bacteria in the mn, mm, and ma groups. 35873450 10 83 dep samples 1858:1864 arg1 farther 1836:1842 farther 1836:1842 farther 1836:1842 In contrast, the samples in the mm group were more scattered and farther away from the samples in the mn and ma groups, i.e., the community structure similarity within and between the groups was low. 35873450 3 84 theme composition 617:627 arg1 diversity 546:554 the diversity 542:554 the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD 542:644 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 2 85 theme Previous 270:277 arg1 research 279:286 Previous research 270:286 Previous research 270:286 Previous research has reported that plant polysaccharides can promote the growth of beneficial intestinal bacteria and inhibit the multiplication of pathogenic bacteria, thus effectively treating diarrhea. 35873450 12 86 theme significant 2216:2226 arg1 differences 2228:2238 significant differences 2216:2238 significant differences in the characteristic bacteria in the mn, mm, and ma groups 2216:2298 In the LEfSe analysis, there were significant differences in the characteristic bacteria in the mn, mm, and ma groups. 35873450 0 87 theme Diarrhea 79:86 arg1 Mice 88:91 Antibiotic-Associated Diarrhea Mice 57:91 Antibiotic-Associated Diarrhea Mice 57:91 The Effect of Qiweibaizhu Powder Crude Polysaccharide on Antibiotic-Associated Diarrhea Mice Is Associated With Restoring Intestinal Mucosal Bacteria. 35873450 8 88 theme groups 1633:1638 arg1 indices 1612:1618 the diversity indices 1598:1618 the diversity indices of all three groups 1598:1638 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 1 89 theme Qiweibaizhu 162:172 arg1 powder 174:179 Background Qiweibaizhu powder 151:179 Background Qiweibaizhu powder (QWBZP) 151:187 Background Qiweibaizhu powder (QWBZP) has been shown to be effective in treating antibiotic-associated diarrhea (AAD). 35873450 1 89 theme Qiweibaizhu 162:172 arg1 QWBZP 182:186 QWBZP 182:186 QWBZP 182:186 Background Qiweibaizhu powder (QWBZP) has been shown to be effective in treating antibiotic-associated diarrhea (AAD). 35873450 4 90 theme treatment 925:933 arg1 group 940:944 the QWBZP crude polysaccharide treatment (ma) group 894:944 the QWBZP crude polysaccharide treatment (ma) group 894:944 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 4 91 theme ma 936:937 arg1 group 940:944 the QWBZP crude polysaccharide treatment (ma) group 894:944 the QWBZP crude polysaccharide treatment (ma) group 894:944 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 0 92 from Effect 4:9 arg1 Mice 88:91 Antibiotic-Associated Diarrhea Mice 57:91 Antibiotic-Associated Diarrhea Mice 57:91 The Effect of Qiweibaizhu Powder Crude Polysaccharide on Antibiotic-Associated Diarrhea Mice Is Associated With Restoring Intestinal Mucosal Bacteria. 35873450 10 93 from samples 1788:1794 arg1 group 1806:1810 the mm group 1799:1810 the mm group 1799:1810 In contrast, the samples in the mm group were more scattered and farther away from the samples in the mn and ma groups, i.e., the community structure similarity within and between the groups was low. 35873450 5 94 theme crude 1063:1067 arg1 solution 1084:1091 gavage crude polysaccharide solution 1056:1091 gavage crude polysaccharide solution of QWBZP 1056:1100 An AAD model was constructed using a mixed antibiotic solution and treated with gavage crude polysaccharide solution of QWBZP. 35873450 11 95 theme Proteobacteria 2025:2038 arg1 abundance 2012:2020 the relative abundance 1999:2020 the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group 1999:2115 Compared with the mm group, the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group was decreased, while that of Enterococcus continued to increase. 35873450 6 96 theme intestinal 1272:1281 arg1 bacteria 1291:1298 the intestinal mucosal bacteria 1268:1298 the intestinal mucosal bacteria in mice 1268:1306 The intestinal mucosa was extracted from the jejunum to the ileum of mice, and the metagenome was extracted and then analyzed using MiSeq sequencing to characterize the intestinal mucosal bacteria in mice. 35873450 5 97 theme antibiotic 1019:1028 arg1 solution 1030:1037 a mixed antibiotic solution 1011:1037 a mixed antibiotic solution 1011:1037 An AAD model was constructed using a mixed antibiotic solution and treated with gavage crude polysaccharide solution of QWBZP. 35873450 4 98 theme crude 904:908 arg1 group 940:944 the QWBZP crude polysaccharide treatment (ma) group 894:944 the QWBZP crude polysaccharide treatment (ma) group 894:944 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 0 99 theme Intestinal 122:131 arg1 Bacteria 141:148 Intestinal Mucosal Bacteria 122:148 Intestinal Mucosal Bacteria 122:148 The Effect of Qiweibaizhu Powder Crude Polysaccharide on Antibiotic-Associated Diarrhea Mice Is Associated With Restoring Intestinal Mucosal Bacteria. 35873450 13 100 theme polysaccharide 2329:2342 arg1 component 2344:2352 The single crude polysaccharide component 2312:2352 The single crude polysaccharide component 2312:2352 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 13 100 theme polysaccharide 2329:2342 arg1 effective 2366:2374 effective 2366:2374 effective 2366:2374 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 8 101 theme groups 1444:1449 arg1 similar 1456:1462 similar 1456:1462 similar 1456:1462 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 8 101 theme groups 1444:1449 arg1 indices 1419:1425 The Chao1 and ACE indices 1401:1425 indices 1419:1425 The Chao1 and ACE indices of the mn and mm groups were similar, the Simpson index was the largest and the Shannon index was the smallest in the mm group, and there was no significant difference in the diversity indices of all three groups. 35873450 0 102 theme Qiweibaizhu 14:24 arg1 Polysaccharide 39:52 Qiweibaizhu Powder Crude Polysaccharide 14:52 Qiweibaizhu Powder Crude Polysaccharide 14:52 The Effect of Qiweibaizhu Powder Crude Polysaccharide on Antibiotic-Associated Diarrhea Mice Is Associated With Restoring Intestinal Mucosal Bacteria. 35873450 12 103 from differences 2228:2238 arg1 mm 2282:2283 the mn, mm, and ma groups 2274:2298 mm 2282:2283 In the LEfSe analysis, there were significant differences in the characteristic bacteria in the mn, mm, and ma groups. 35873450 12 103 from differences 2228:2238 arg1 bacteria 2262:2269 the characteristic bacteria 2243:2269 the characteristic bacteria 2243:2269 In the LEfSe analysis, there were significant differences in the characteristic bacteria in the mn, mm, and ma groups. 35873450 12 103 from differences 2228:2238 arg1 groups 2293:2298 the mn, mm, and ma groups 2274:2298 groups 2293:2298 In the LEfSe analysis, there were significant differences in the characteristic bacteria in the mn, mm, and ma groups. 35873450 0 104 theme Crude 33:37 arg1 Polysaccharide 39:52 Qiweibaizhu Powder Crude Polysaccharide 14:52 Qiweibaizhu Powder Crude Polysaccharide 14:52 The Effect of Qiweibaizhu Powder Crude Polysaccharide on Antibiotic-Associated Diarrhea Mice Is Associated With Restoring Intestinal Mucosal Bacteria. 35873450 4 105 from mice 956:959 arg1 group 969:973 each group 964:973 each group 964:973 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 2 106 theme bacteria 430:437 arg1 multiplication 401:414 the multiplication 397:414 the multiplication of pathogenic bacteria 397:437 Previous research has reported that plant polysaccharides can promote the growth of beneficial intestinal bacteria and inhibit the multiplication of pathogenic bacteria, thus effectively treating diarrhea. 35873450 13 107 theme single 2316:2321 arg1 component 2344:2352 The single crude polysaccharide component 2312:2352 The single crude polysaccharide component 2312:2352 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 13 107 theme single 2316:2321 arg1 effective 2366:2374 effective 2366:2374 effective 2366:2374 Conclusion The single crude polysaccharide component is not very effective in treating AAD, so the clinical efficacy of the QWBZP crude polysaccharide is subject to further investigation. 35873450 10 108 dep similarity 1921:1930 arg1 i.e. 1891:1894 i.e. 1891:1894 i.e. 1891:1894 In contrast, the samples in the mm group were more scattered and farther away from the samples in the mn and ma groups, i.e., the community structure similarity within and between the groups was low. 35873450 9 109 theme ma 1673:1674 arg1 samples 1682:1688 the mn and ma group samples 1662:1688 samples 1682:1688 In the PCA and PCoA, the mn and ma group samples were both relatively concentrated with a high similarity of community structure. 35873450 12 110 theme LEfSe 2189:2193 arg1 analysis 2195:2202 the LEfSe analysis 2185:2202 the LEfSe analysis 2185:2202 In the LEfSe analysis, there were significant differences in the characteristic bacteria in the mn, mm, and ma groups. 35873450 3 111 theme crude 518:522 arg1 polysaccharide 524:537 QWBZP crude polysaccharide 512:537 QWBZP crude polysaccharide 512:537 Here, we investigated the effect of QWBZP crude polysaccharide on the diversity of intestinal mucosal bacteria and their community structure composition in mice with AAD, and the aim of this study was to provide the scientific basis for the efficacy of QWBZP crude polysaccharide on diarrhea. 35873450 11 112 theme relative 2003:2010 arg1 abundance 2012:2020 the relative abundance 1999:2020 the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group 1999:2115 Compared with the mm group, the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group was decreased, while that of Enterococcus continued to increase. 35873450 5 113 theme QWBZP 1096:1100 arg1 solution 1084:1091 gavage crude polysaccharide solution 1056:1091 gavage crude polysaccharide solution of QWBZP 1056:1100 An AAD model was constructed using a mixed antibiotic solution and treated with gavage crude polysaccharide solution of QWBZP. 35873450 10 114 from samples 1858:1864 arg1 groups 1883:1888 the mn and ma groups 1869:1888 groups 1883:1888 In contrast, the samples in the mm group were more scattered and farther away from the samples in the mn and ma groups, i.e., the community structure similarity within and between the groups was low. 35873450 10 115 theme mn 1873:1874 arg1 groups 1883:1888 the mn and ma groups 1869:1888 groups 1883:1888 In contrast, the samples in the mm group were more scattered and farther away from the samples in the mn and ma groups, i.e., the community structure similarity within and between the groups was low. 35873450 4 116 theme Kunming 800:806 arg1 mice 813:816 Eighteen Kunming (KM) mice 791:816 Eighteen Kunming (KM) mice 791:816 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35873450 1 117 theme antibiotic-associated 232:252 arg1 diarrhea 254:261 antibiotic-associated diarrhea 232:261 antibiotic-associated diarrhea (AAD) 232:267 Background Qiweibaizhu powder (QWBZP) has been shown to be effective in treating antibiotic-associated diarrhea (AAD). 35873450 1 117 theme antibiotic-associated 232:252 arg1 AAD 264:266 AAD 264:266 AAD 264:266 Background Qiweibaizhu powder (QWBZP) has been shown to be effective in treating antibiotic-associated diarrhea (AAD). 35873450 11 118 theme ratio 2095:2099 arg1 abundance 2012:2020 the relative abundance 1999:2020 the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group 1999:2115 Compared with the mm group, the relative abundance of Proteobacteria, Lactobacillus, and the Firmicutes/Bacteroidetes (F/B) ratio in the ma group was decreased, while that of Enterococcus continued to increase. 35873450 4 119 theme KM 809:810 arg1 mice 813:816 Eighteen Kunming (KM) mice 791:816 Eighteen Kunming (KM) mice 791:816 Materials and Methods Eighteen Kunming (KM) mice were randomly divided into the normal (mn) group, the model (mm) group, and the QWBZP crude polysaccharide treatment (ma) group, with six mice in each group. 35463390 11 0 from perspective 1982:1992 arg1 sections 1929:1936 the exposed atmospheric sections 1905:1936 the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects 1905:2017 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 11 0 from perspective 1982:1992 arg1 factors 1893:1899 atmospheric factors 1881:1899 atmospheric factors 1881:1899 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 10 1 theme turning 1722:1728 arg1 times 1670:1674 Exposure times 1661:1674 Exposure times between 5 and 7 years 1661:1696 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 10 1 theme turning 1722:1728 arg1 point 1730:1734 the most important turning point 1703:1734 the most important turning point in time for determining the deterioration of the S. psammophila sand barrier 1703:1811 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 9 2 theme several 1646:1652 arg1 years 1654:1658 several years 1646:1658 several years 1646:1658 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 35463390 13 3 theme sand 2235:2238 arg1 barrier 2240:2246 S. psammophila sand barrier 2220:2246 S. psammophila sand barrier 2220:2246 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 1 4 theme Salix 186:190 arg1 Barrier 209:215 Salix psammophila Sand Barrier 186:215 Salix psammophila Sand Barrier 186:215 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 4 5 theme composition 657:667 arg1 changes 669:675 The relative crystallinity and chemical composition changes 617:675 The relative crystallinity and chemical composition changes in the sand barrier 617:695 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 1 6 theme Sand 204:207 arg1 Barrier 209:215 Salix psammophila Sand Barrier 186:215 Salix psammophila Sand Barrier 186:215 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 5 7 theme ultraviolet 1020:1030 arg1 radiation 1032:1040 ultraviolet radiation 1020:1040 ultraviolet radiation 1020:1040 The results showed that the degradation degree of the exposed S. psammophila sand barrier was mainly affected by moisture and ultraviolet radiation. 35463390 3 8 theme key 526:528 arg1 factors 530:536 key factors 526:536 key factors in the desert atmospheric environment 526:574 Then, we assessed how key factors in the desert atmospheric environment affect structural aging and performance. 35463390 13 9 theme desert 2329:2334 arg1 environments 2336:2347 stressful desert environments 2319:2347 stressful desert environments 2319:2347 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 4 10 theme relative 621:628 arg1 crystallinity 630:642 The relative crystallinity 617:642 The relative crystallinity 617:642 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 11 11 theme S. 1945:1946 arg1 barrier 1965:1971 the S. psammophila sand barrier 1941:1971 the S. psammophila sand barrier 1941:1971 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 4 12 theme degradation 844:854 arg1 factors 856:862 the main degradation factors 835:862 the main degradation factors 835:862 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 8 13 theme S. 1428:1429 arg1 barrier 1448:1454 S. psammophila sand barrier 1428:1454 S. psammophila sand barrier 1428:1454 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 12 14 theme sand 2057:2060 arg1 deterioration 2070:2082 the sand barrier deterioration 2053:2082 the sand barrier deterioration 2053:2082 However, the exact mechanisms of the sand barrier deterioration still need further investigation. 35463390 3 15 theme desert 545:550 arg1 environment 564:574 the desert atmospheric environment 541:574 the desert atmospheric environment 541:574 Then, we assessed how key factors in the desert atmospheric environment affect structural aging and performance. 35463390 1 16 theme desert 130:135 arg1 environments 137:148 desert environments 130:148 desert environments 130:148 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 8 17 theme sand 1443:1446 arg1 barrier 1448:1454 S. psammophila sand barrier 1428:1454 S. psammophila sand barrier 1428:1454 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 12 18 theme deterioration 2070:2082 arg1 mechanisms 2039:2048 the exact mechanisms 2029:2048 the exact mechanisms of the sand barrier deterioration 2029:2082 However, the exact mechanisms of the sand barrier deterioration still need further investigation. 35463390 10 19 theme sand 1800:1803 arg1 barrier 1805:1811 the S. psammophila sand barrier 1781:1811 the S. psammophila sand barrier 1781:1811 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 10 20 from point 1730:1734 arg1 time 1739:1742 time 1739:1742 time 1739:1742 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 2 21 theme S. 475:476 arg1 barrier 495:501 S. psammophila sand barrier 475:501 S. psammophila sand barrier 475:501 In this study, we have first examined the key environmental factors that affect the exposure of S. psammophila sand barrier. 35463390 11 22 theme exposed 1909:1915 arg1 sections 1929:1936 the exposed atmospheric sections 1905:1936 the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects 1905:2017 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 12 23 theme exact 2033:2037 arg1 mechanisms 2039:2048 the exact mechanisms 2029:2048 the exact mechanisms of the sand barrier deterioration 2029:2082 However, the exact mechanisms of the sand barrier deterioration still need further investigation. 35463390 10 24 theme S. 1785:1786 arg1 barrier 1805:1811 the S. psammophila sand barrier 1781:1811 the S. psammophila sand barrier 1781:1811 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 9 25 theme irreversible 1483:1494 arg1 changes 1496:1502 irreversible changes 1483:1502 irreversible changes 1483:1502 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 35463390 0 26 from Processes 22:30 arg1 Section 91:97 Atmospheric Exposure Section 70:97 Atmospheric Exposure Section 70:97 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 35463390 4 27 theme sand 684:687 arg1 barrier 689:695 the sand barrier 680:695 the sand barrier 680:695 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 0 28 theme Exposure 82:89 arg1 Section 91:97 Atmospheric Exposure Section 70:97 Atmospheric Exposure Section 70:97 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 35463390 13 29 theme desertification 2279:2293 arg1 reversal 2295:2302 desertification reversal 2279:2302 desertification reversal 2279:2302 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 7 30 theme other 1170:1174 arg1 hemicellulose 1215:1227 hemicellulose 1215:1227 hemicellulose 1215:1227 However, other polysaccharides, such as cellulose and hemicellulose, were less affected by photodegradation. 35463390 7 30 theme other 1170:1174 arg1 cellulose 1201:1209 cellulose 1201:1209 cellulose 1201:1209 However, other polysaccharides, such as cellulose and hemicellulose, were less affected by photodegradation. 35463390 7 30 theme other 1170:1174 arg1 polysaccharides 1176:1190 other polysaccharides 1170:1190 other polysaccharides 1170:1190 However, other polysaccharides, such as cellulose and hemicellulose, were less affected by photodegradation. 35463390 1 31 theme proofing 344:351 arg1 benefits 369:376 their wind proofing and sand fixing benefits 333:376 their wind proofing and sand fixing benefits 333:376 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 11 32 theme environmental 1997:2009 arg1 effects 2011:2017 environmental effects 1997:2017 environmental effects 1997:2017 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 5 33 theme degradation 922:932 arg1 degree 934:939 the degradation degree 918:939 the degradation degree of the exposed S. psammophila sand barrier 918:982 The results showed that the degradation degree of the exposed S. psammophila sand barrier was mainly affected by moisture and ultraviolet radiation. 35463390 2 34 theme sand 490:493 arg1 barrier 495:501 S. psammophila sand barrier 475:501 S. psammophila sand barrier 475:501 In this study, we have first examined the key environmental factors that affect the exposure of S. psammophila sand barrier. 35463390 11 35 theme atmospheric 1881:1891 arg1 factors 1893:1899 atmospheric factors 1881:1899 atmospheric factors 1881:1899 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 1 36 theme sand 357:360 arg1 benefits 369:376 their wind proofing and sand fixing benefits 333:376 their wind proofing and sand fixing benefits 333:376 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 2 37 theme key 421:423 arg1 factors 439:445 the key environmental factors 417:445 the key environmental factors that affect the exposure of S. psammophila sand barrier 417:501 In this study, we have first examined the key environmental factors that affect the exposure of S. psammophila sand barrier. 35463390 11 38 theme interactions 1860:1871 arg1 importance 1842:1851 the importance 1838:1851 the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects 1838:2017 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 0 39 theme Natural 0:6 arg1 Processes 22:30 Natural Deterioration Processes 0:30 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 0:98 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 35463390 13 40 theme psammophila 2223:2233 arg1 barrier 2240:2246 S. psammophila sand barrier 2220:2246 S. psammophila sand barrier 2220:2246 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 13 41 from advanced 2153:2160 arg1 environments 2336:2347 stressful desert environments 2319:2347 stressful desert environments 2319:2347 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 5 42 theme sand 971:974 arg1 barrier 976:982 the exposed S. psammophila sand barrier 944:982 the exposed S. psammophila sand barrier 944:982 The results showed that the degradation degree of the exposed S. psammophila sand barrier was mainly affected by moisture and ultraviolet radiation. 35463390 10 43 theme Exposure 1661:1668 arg1 times 1670:1674 Exposure times 1661:1674 Exposure times between 5 and 7 years 1661:1696 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 10 43 theme Exposure 1661:1668 arg1 point 1730:1734 the most important turning point 1703:1734 the most important turning point in time for determining the deterioration of the S. psammophila sand barrier 1703:1811 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 13 44 theme barrier 2240:2246 arg1 effects 2209:2215 the environmental effects 2191:2215 the environmental effects of S. psammophila sand barrier 2191:2246 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 9 45 theme natural 1549:1555 arg1 properties 1566:1575 the natural material properties 1545:1575 the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years 1545:1658 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 35463390 0 46 theme Salix 35:39 arg1 Barriers 58:65 Salix psammophila Sand Barriers 35:65 Salix psammophila Sand Barriers 35:65 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 35463390 1 47 theme barrier 303:309 arg1 performance 279:289 performance 279:289 performance 279:289 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 1 47 theme barrier 303:309 arg1 structure 265:273 structure 265:273 structure 265:273 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 5 48 theme barrier 976:982 arg1 degree 934:939 the degradation degree 918:939 the degradation degree of the exposed S. psammophila sand barrier 918:982 The results showed that the degradation degree of the exposed S. psammophila sand barrier was mainly affected by moisture and ultraviolet radiation. 35463390 13 49 theme environmental 2195:2207 arg1 effects 2209:2215 the environmental effects 2191:2215 the environmental effects of S. psammophila sand barrier 2191:2246 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 4 50 theme X-ray 791:795 arg1 XPS 825:827 XPS 825:827 XPS 825:827 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 4 50 theme X-ray 791:795 arg1 spectroscopy 811:822 X-ray photoelectron spectroscopy 791:822 X-ray photoelectron spectroscopy (XPS) 791:828 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 0 51 theme Sand 53:56 arg1 Barriers 58:65 Salix psammophila Sand Barriers 35:65 Salix psammophila Sand Barriers 35:65 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 35463390 9 52 theme S. 1580:1581 arg1 barrier 1600:1606 S. psammophila sand barrier 1580:1606 S. psammophila sand barrier exposed to atmospheric conditions for several years 1580:1658 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 35463390 3 53 theme structural 583:592 arg1 aging 594:598 structural aging 583:598 structural aging 583:598 Then, we assessed how key factors in the desert atmospheric environment affect structural aging and performance. 35463390 13 54 theme current 2166:2172 arg1 understanding 2174:2186 the current understanding 2162:2186 the current understanding of the environmental effects of S. psammophila sand barrier 2162:2246 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 5 55 theme exposed 948:954 arg1 barrier 976:982 the exposed S. psammophila sand barrier 944:982 the exposed S. psammophila sand barrier 944:982 The results showed that the degradation degree of the exposed S. psammophila sand barrier was mainly affected by moisture and ultraviolet radiation. 35463390 4 56 dep Fourier 739:745 arg1 transform 747:755 transform 747:755 transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) 747:828 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 6 57 located observed 1131:1138 arg2 photodegradation 1091:1106 photodegradation 1091:1106 photodegradation 1091:1106 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 6 57 located observed 1131:1138 arg1 barrier 1152:1158 the sand barrier 1143:1158 the sand barrier 1143:1158 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 10 58 dep S. 1785:1786 arg1 psammophila 1788:1798 psammophila 1788:1798 psammophila 1788:1798 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 5 59 theme psammophila 959:969 arg1 barrier 976:982 the exposed S. psammophila sand barrier 944:982 the exposed S. psammophila sand barrier 944:982 The results showed that the degradation degree of the exposed S. psammophila sand barrier was mainly affected by moisture and ultraviolet radiation. 35463390 6 60 theme main 1058:1061 arg1 component 1063:1071 the main component 1054:1071 the main component 1054:1071 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 6 60 theme main 1058:1061 arg1 Lignin 1043:1048 Lignin 1043:1048 Lignin 1043:1048 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 13 61 theme overall 2136:2142 arg1 findings 2144:2151 our overall findings 2132:2151 our overall findings 2132:2151 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 9 62 theme atmospheric 1619:1629 arg1 conditions 1631:1640 atmospheric conditions 1619:1640 atmospheric conditions 1619:1640 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 35463390 4 63 from changes 669:675 arg1 barrier 689:695 the sand barrier 680:695 the sand barrier 680:695 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 6 64 theme sand 1147:1150 arg1 barrier 1152:1158 the sand barrier 1143:1158 the sand barrier 1143:1158 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 10 65 theme important 1712:1720 arg1 times 1670:1674 Exposure times 1661:1674 Exposure times between 5 and 7 years 1661:1696 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 10 65 theme important 1712:1720 arg1 point 1730:1734 the most important turning point 1703:1734 the most important turning point in time for determining the deterioration of the S. psammophila sand barrier 1703:1811 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 11 66 theme sand 1960:1963 arg1 barrier 1965:1971 the S. psammophila sand barrier 1941:1971 the S. psammophila sand barrier 1941:1971 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 4 67 theme photoelectron 797:809 arg1 XPS 825:827 XPS 825:827 XPS 825:827 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 4 67 theme photoelectron 797:809 arg1 spectroscopy 811:822 X-ray photoelectron spectroscopy 791:822 X-ray photoelectron spectroscopy (XPS) 791:828 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 4 68 theme crystallinity 630:642 arg1 changes 669:675 The relative crystallinity and chemical composition changes 617:675 The relative crystallinity and chemical composition changes in the sand barrier 617:695 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 1 69 theme psammophila 192:202 arg1 Barrier 209:215 Salix psammophila Sand Barrier 186:215 Salix psammophila Sand Barrier 186:215 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 6 70 theme photodiscoloration 1112:1129 arg1 component 1063:1071 the main component 1054:1071 the main component 1054:1071 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 6 70 theme photodiscoloration 1112:1129 arg1 source 1081:1086 the source 1077:1086 the source of photodegradation and photodiscoloration observed in the sand barrier 1077:1158 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 6 70 theme photodiscoloration 1112:1129 arg1 Lignin 1043:1048 Lignin 1043:1048 Lignin 1043:1048 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 4 71 theme chemical 648:655 arg1 composition 657:667 chemical composition 648:667 chemical composition 648:667 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 11 72 theme effects 2011:2017 arg1 perspective 1982:1992 the perspective 1978:1992 the perspective of environmental effects 1978:2017 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 1 73 theme Barrier 209:215 arg1 protection 172:181 the protection 168:181 the protection of Salix psammophila Sand Barrier 168:215 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 6 74 theme photodegradation 1091:1106 arg1 component 1063:1071 the main component 1054:1071 the main component 1054:1071 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 6 74 theme photodegradation 1091:1106 arg1 source 1081:1086 the source 1077:1086 the source of photodegradation and photodiscoloration observed in the sand barrier 1077:1158 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 6 74 theme photodegradation 1091:1106 arg1 Lignin 1043:1048 Lignin 1043:1048 Lignin 1043:1048 Lignin was the main component and the source of photodegradation and photodiscoloration observed in the sand barrier. 35463390 3 75 theme atmospheric 552:562 arg1 environment 564:574 the desert atmospheric environment 541:574 the desert atmospheric environment 541:574 Then, we assessed how key factors in the desert atmospheric environment affect structural aging and performance. 35463390 8 76 theme psammophila 1431:1441 arg1 barrier 1448:1454 S. psammophila sand barrier 1428:1454 S. psammophila sand barrier 1428:1454 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 12 77 theme further 2095:2101 arg1 investigation 2103:2115 further investigation 2095:2115 further investigation 2095:2115 However, the exact mechanisms of the sand barrier deterioration still need further investigation. 35463390 11 78 theme barrier 1965:1971 arg1 sections 1929:1936 the exposed atmospheric sections 1905:1936 the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects 1905:2017 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 11 78 theme barrier 1965:1971 arg1 factors 1893:1899 atmospheric factors 1881:1899 atmospheric factors 1881:1899 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 8 79 dep warping 1408:1414 arg1 observed 1416:1423 observed 1416:1423 warping observed in S. psammophila sand barrier 1408:1454 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 4 80 theme main 839:842 arg1 factors 856:862 the main degradation factors 835:862 the main degradation factors 835:862 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 1 81 dep structure 265:273 arg1 the 261:263 the 261:263 the 261:263 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 10 82 theme barrier 1805:1811 arg1 deterioration 1764:1776 the deterioration 1760:1776 the deterioration of the S. psammophila sand barrier 1760:1811 Exposure times between 5 and 7 years were the most important turning point in time for determining the deterioration of the S. psammophila sand barrier. 35463390 1 83 theme environments 137:148 arg1 important 154:162 important 154:162 important 154:162 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 1 83 theme environments 137:148 arg1 conditions 116:125 The atmospheric conditions 100:125 The atmospheric conditions of desert environments 100:148 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 12 84 theme barrier 2062:2068 arg1 deterioration 2070:2082 the sand barrier deterioration 2053:2082 the sand barrier deterioration 2053:2082 However, the exact mechanisms of the sand barrier deterioration still need further investigation. 35463390 3 85 from factors 530:536 arg1 environment 564:574 the desert atmospheric environment 541:574 the desert atmospheric environment 541:574 Then, we assessed how key factors in the desert atmospheric environment affect structural aging and performance. 35463390 0 86 theme Atmospheric 70:80 arg1 Section 91:97 Atmospheric Exposure Section 70:97 Atmospheric Exposure Section 70:97 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 35463390 11 87 theme psammophila 1948:1958 arg1 barrier 1965:1971 the S. psammophila sand barrier 1941:1971 the S. psammophila sand barrier 1941:1971 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 8 88 dep cause 1341:1345 arg1 cracking 1394:1401 cracking 1394:1401 cracking 1394:1401 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 8 88 dep cause 1341:1345 arg1 warping 1408:1414 warping 1408:1414 warping observed in S. psammophila sand barrier 1408:1454 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 13 89 theme ecological 2252:2261 arg1 restoration 2263:2273 ecological restoration 2252:2273 ecological restoration 2252:2273 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 9 90 theme changes 1496:1502 arg1 series 1473:1478 a series 1471:1478 a series 1471:1478 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 35463390 1 91 theme wind 339:342 arg1 benefits 369:376 their wind proofing and sand fixing benefits 333:376 their wind proofing and sand fixing benefits 333:376 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 9 92 theme losses 1508:1513 arg1 series 1473:1478 a series 1471:1478 a series 1471:1478 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 35463390 13 93 theme stressful 2319:2327 arg1 environments 2336:2347 stressful desert environments 2319:2347 stressful desert environments 2319:2347 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 2 94 theme barrier 495:501 arg1 exposure 463:470 the exposure 459:470 the exposure of S. psammophila sand barrier 459:501 In this study, we have first examined the key environmental factors that affect the exposure of S. psammophila sand barrier. 35463390 2 95 theme psammophila 478:488 arg1 barrier 495:501 S. psammophila sand barrier 475:501 S. psammophila sand barrier 475:501 In this study, we have first examined the key environmental factors that affect the exposure of S. psammophila sand barrier. 35463390 8 96 theme main 1336:1339 arg1 stress 1274:1279 The stress 1270:1279 The stress generated by alternating desorption-absorption 1270:1326 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 8 96 theme main 1336:1339 arg1 cause 1341:1345 the main cause 1332:1345 the main cause of the expansion and contraction, deformation 1332:1391 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 0 97 theme Deterioration 8:20 arg1 Processes 22:30 Natural Deterioration Processes 0:30 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 0:98 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 35463390 9 98 theme sand 1595:1598 arg1 barrier 1600:1606 S. psammophila sand barrier 1580:1606 S. psammophila sand barrier exposed to atmospheric conditions for several years 1580:1658 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 35463390 4 99 theme X-ray 714:718 arg1 XRD 733:735 XRD 733:735 XRD 733:735 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 4 99 theme X-ray 714:718 arg1 Fourier 739:745 Fourier 739:745 Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) 739:828 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 4 99 theme X-ray 714:718 arg1 diffraction 720:730 X-ray diffraction 714:730 X-ray diffraction (XRD) 714:736 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 5 100 theme S. 956:957 arg1 barrier 976:982 the exposed S. psammophila sand barrier 944:982 the exposed S. psammophila sand barrier 944:982 The results showed that the degradation degree of the exposed S. psammophila sand barrier was mainly affected by moisture and ultraviolet radiation. 35463390 1 101 theme atmospheric 104:114 arg1 important 154:162 important 154:162 important 154:162 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 1 101 theme atmospheric 104:114 arg1 conditions 116:125 The atmospheric conditions 100:125 The atmospheric conditions of desert environments 100:148 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 8 102 theme expansion 1354:1362 arg1 stress 1274:1279 The stress 1270:1279 The stress generated by alternating desorption-absorption 1270:1326 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 8 102 theme expansion 1354:1362 arg1 cause 1341:1345 the main cause 1332:1345 the main cause of the expansion and contraction, deformation 1332:1391 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 11 103 theme atmospheric 1917:1927 arg1 sections 1929:1936 the exposed atmospheric sections 1905:1936 the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects 1905:2017 Our results highlighted the importance of the interactions between atmospheric factors and the exposed atmospheric sections of the S. psammophila sand barrier from the perspective of environmental effects. 35463390 0 104 theme psammophila 41:51 arg1 Barriers 58:65 Salix psammophila Sand Barriers 35:65 Salix psammophila Sand Barriers 35:65 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 35463390 1 105 theme sand 298:301 arg1 barrier 303:309 the sand barrier 294:309 the sand barrier 294:309 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 9 106 theme material 1557:1564 arg1 properties 1566:1575 the natural material properties 1545:1575 the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years 1545:1658 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 35463390 8 107 theme contraction 1368:1378 arg1 stress 1274:1279 The stress 1270:1279 The stress generated by alternating desorption-absorption 1270:1326 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 8 107 theme contraction 1368:1378 arg1 cause 1341:1345 the main cause 1332:1345 the main cause of the expansion and contraction, deformation 1332:1391 The stress generated by alternating desorption-absorption was the main cause of the expansion and contraction, deformation, cracking, and warping observed in S. psammophila sand barrier. 35463390 13 108 from environments 2336:2347 arg1 advanced 2153:2160 advanced 2153:2160 advanced 2153:2160 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 0 109 theme Barriers 58:65 arg1 Processes 22:30 Natural Deterioration Processes 0:30 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 0:98 Natural Deterioration Processes of Salix psammophila Sand Barriers in Atmospheric Exposure Section. 35463390 13 110 theme effects 2209:2215 arg1 understanding 2174:2186 the current understanding 2162:2186 the current understanding of the environmental effects of S. psammophila sand barrier 2162:2246 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 2 111 theme environmental 425:437 arg1 factors 439:445 the key environmental factors 417:445 the key environmental factors that affect the exposure of S. psammophila sand barrier 417:501 In this study, we have first examined the key environmental factors that affect the exposure of S. psammophila sand barrier. 35463390 1 112 dep proofing 344:351 arg1 fixing 362:367 fixing 362:367 fixing 362:367 The atmospheric conditions of desert environments are important for the protection of Salix psammophila Sand Barrier, and these conditions can affect and change the structure and performance of the sand barrier, causing them to lose their wind proofing and sand fixing benefits. 35463390 13 113 theme S. 2220:2221 arg1 barrier 2240:2246 S. psammophila sand barrier 2220:2246 S. psammophila sand barrier 2220:2246 Nevertheless, our overall findings advanced the current understanding of the environmental effects of S. psammophila sand barrier for ecological restoration and desertification reversal, especially in stressful desert environments. 35463390 9 114 theme psammophila 1583:1593 arg1 barrier 1600:1606 S. psammophila sand barrier 1580:1606 S. psammophila sand barrier exposed to atmospheric conditions for several years 1580:1658 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 35463390 4 115 theme infrared 757:764 arg1 FTIR 780:783 FTIR 780:783 FTIR 780:783 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 4 115 theme infrared 757:764 arg1 spectroscopy 766:777 infrared spectroscopy 757:777 infrared spectroscopy (FTIR) 757:784 The relative crystallinity and chemical composition changes in the sand barrier were measured by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), and the main degradation factors and processes were discussed. 35463390 9 116 theme barrier 1600:1606 arg1 properties 1566:1575 the natural material properties 1545:1575 the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years 1545:1658 We also found a series of irreversible changes and losses that occurred, which affected the natural material properties of S. psammophila sand barrier exposed to atmospheric conditions for several years. 37120200 2 0 theme molecular 463:471 arg1 compounds 480:488 low molecular weight compounds 459:488 low molecular weight compounds 459:488 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 1 theme MALDI-TOF 341:349 arg1 spectrometry 327:338 matrix-assisted laser desorption/ionization imaging mass spectrometry 270:338 matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) 270:354 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 1 theme MALDI-TOF 341:349 arg1 MSI 351:353 MALDI-TOF MSI 341:353 MALDI-TOF MSI 341:353 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 0 2 theme garlic 71:76 arg1 analysis 49:56 the composition analysis 33:56 the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS 33:140 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 3 3 theme pigment 688:694 arg1 precursors 696:705 pigment precursors 688:705 pigment precursors 688:705 The distribution characteristics of the compounds were observed in processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins. 37120200 1 4 theme Laba 143:146 arg1 garlic 148:153 Laba garlic 143:153 Laba garlic 143:153 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 1 4 theme Laba 143:146 arg1 kind 160:163 a kind 158:163 a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects 158:248 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 3 5 located observed 580:587 arg1 garlic 618:623 processed and unprocessed garlic 592:623 processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins 592:735 The distribution characteristics of the compounds were observed in processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins. 37120200 3 5 located observed 580:587 arg2 characteristics 542:556 The distribution characteristics 525:556 The distribution characteristics of the compounds 525:573 The distribution characteristics of the compounds were observed in processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins. 37120200 1 6 theme product 213:219 arg1 garlic 148:153 Laba garlic 143:153 Laba garlic 143:153 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 1 6 theme product 213:219 arg1 kind 160:163 a kind 158:163 a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects 158:248 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 0 7 theme imaging 91:97 arg1 MSI 118:120 MSI 118:120 MSI 118:120 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 0 7 theme imaging 91:97 arg1 spectrometry 104:115 MALDI-TOF imaging mass spectrometry 81:115 MALDI-TOF imaging mass spectrometry (MSI) 81:121 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 3 8 theme compounds 565:573 arg1 characteristics 542:556 The distribution characteristics 525:556 The distribution characteristics of the compounds 525:573 The distribution characteristics of the compounds were observed in processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins. 37120200 4 9 theme bioactive 774:782 arg1 saponins 813:820 saponins 813:820 saponins 813:820 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 4 9 theme bioactive 774:782 arg1 compounds 784:792 some bioactive compounds 769:792 some bioactive compounds such as alliin and saponins 769:820 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 4 9 theme bioactive 774:782 arg1 alliin 802:807 alliin 802:807 alliin 802:807 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 4 10 theme pigments-related 958:973 arg1 compounds 975:983 pigments-related compounds 958:983 pigments-related compounds 958:983 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 0 11 theme MALDI-TOF 81:89 arg1 MSI 118:120 MSI 118:120 MSI 118:120 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 0 11 theme MALDI-TOF 81:89 arg1 spectrometry 104:115 MALDI-TOF imaging mass spectrometry 81:115 MALDI-TOF imaging mass spectrometry (MSI) 81:121 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 5 12 theme garlic 1107:1112 arg1 processing 1114:1123 Laba garlic processing 1102:1123 Laba garlic processing 1102:1123 This study provided a basis for the spatial distributions and changes of compounds in garlic tissue during Laba garlic processing, which suggested that the bioactivities of garlic might be changed after processing owing to the transformation and change of the constituents. 37120200 5 13 theme constituents 1255:1266 arg1 transformation 1222:1235 transformation 1222:1235 transformation 1222:1235 This study provided a basis for the spatial distributions and changes of compounds in garlic tissue during Laba garlic processing, which suggested that the bioactivities of garlic might be changed after processing owing to the transformation and change of the constituents. 37120200 5 13 theme constituents 1255:1266 arg1 change 1241:1246 change 1241:1246 change 1241:1246 This study provided a basis for the spatial distributions and changes of compounds in garlic tissue during Laba garlic processing, which suggested that the bioactivities of garlic might be changed after processing owing to the transformation and change of the constituents. 37120200 3 14 theme distribution 529:540 arg1 characteristics 542:556 The distribution characteristics 525:556 The distribution characteristics of the compounds 525:573 The distribution characteristics of the compounds were observed in processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins. 37120200 1 15 theme multiple 226:233 arg1 effects 242:248 multiple health effects 226:248 multiple health effects 226:248 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 4 16 theme garlic 750:755 arg1 processing 757:766 Laba garlic processing 745:766 Laba garlic processing 745:766 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 5 17 theme Laba 1102:1105 arg1 processing 1114:1123 Laba garlic processing 1102:1123 Laba garlic processing 1102:1123 This study provided a basis for the spatial distributions and changes of compounds in garlic tissue during Laba garlic processing, which suggested that the bioactivities of garlic might be changed after processing owing to the transformation and change of the constituents. 37120200 0 18 theme mass 99:102 arg1 MSI 118:120 MSI 118:120 MSI 118:120 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 0 18 theme mass 99:102 arg1 spectrometry 104:115 MALDI-TOF imaging mass spectrometry 81:115 MALDI-TOF imaging mass spectrometry (MSI) 81:121 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 0 19 theme novel 2:6 arg1 method 22:27 A novel visualization method 0:27 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 0:141 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 2 20 theme low 459:461 arg1 compounds 480:488 low molecular weight compounds 459:488 low molecular weight compounds 459:488 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 4 21 theme other 867:871 arg1 compounds 873:881 other compounds 867:881 other compounds 867:881 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 2 22 theme compounds 480:488 arg1 changes 448:454 the garlic tissue spatial distribution changes 409:454 the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing 409:522 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 23 theme laser 286:290 arg1 spectrometry 327:338 matrix-assisted laser desorption/ionization imaging mass spectrometry 270:338 matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) 270:354 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 23 theme laser 286:290 arg1 MSI 351:353 MALDI-TOF MSI 341:353 MALDI-TOF MSI 341:353 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 24 theme Q-TOF 360:364 arg1 LC-MS/MS 366:373 Q-TOF LC-MS/MS 360:373 Q-TOF LC-MS/MS 360:373 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 25 theme garlic 413:418 arg1 changes 448:454 the garlic tissue spatial distribution changes 409:454 the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing 409:522 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 1 26 theme health 235:240 arg1 effects 242:248 multiple health effects 226:248 multiple health effects 226:248 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 2 27 theme matrix-assisted 270:284 arg1 spectrometry 327:338 matrix-assisted laser desorption/ionization imaging mass spectrometry 270:338 matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) 270:354 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 27 theme matrix-assisted 270:284 arg1 MSI 351:353 MALDI-TOF MSI 341:353 MALDI-TOF MSI 341:353 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 4 28 theme Laba 745:748 arg1 processing 757:766 Laba garlic processing 745:766 Laba garlic processing 745:766 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 0 29 theme visualization 8:20 arg1 method 22:27 A novel visualization method 0:27 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 0:141 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 5 30 theme garlic 1081:1086 arg1 tissue 1088:1093 garlic tissue 1081:1093 garlic tissue 1081:1093 This study provided a basis for the spatial distributions and changes of compounds in garlic tissue during Laba garlic processing, which suggested that the bioactivities of garlic might be changed after processing owing to the transformation and change of the constituents. 37120200 1 31 theme vinegar 168:174 arg1 product 213:219 vinegar processed garlic (Allium sativum L.) product 168:219 vinegar processed garlic (Allium sativum L.) product with multiple health effects 168:248 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 4 32 theme new 934:936 arg1 compounds 938:946 some new compounds 929:946 some new compounds including pigments-related compounds 929:983 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 4 32 theme new 934:936 arg1 compounds 975:983 pigments-related compounds 958:983 pigments-related compounds 958:983 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 2 33 theme first 383:387 arg1 time 389:392 the first time 379:392 the first time 379:392 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 1 34 theme processed 176:184 arg1 product 213:219 vinegar processed garlic (Allium sativum L.) product 168:219 vinegar processed garlic (Allium sativum L.) product with multiple health effects 168:248 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 3 35 theme amino 635:639 arg1 acids 641:645 amino acids 635:645 amino acids 635:645 The distribution characteristics of the compounds were observed in processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins. 37120200 3 36 theme processed 592:600 arg1 garlic 618:623 processed and unprocessed garlic 592:623 processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins 592:735 The distribution characteristics of the compounds were observed in processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins. 37120200 1 37 theme garlic 186:191 arg1 product 213:219 vinegar processed garlic (Allium sativum L.) product 168:219 vinegar processed garlic (Allium sativum L.) product with multiple health effects 168:248 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 2 38 theme distribution 435:446 arg1 changes 448:454 the garlic tissue spatial distribution changes 409:454 the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing 409:522 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 39 theme garlic 506:511 arg1 processing 513:522 the Laba garlic processing 497:522 the Laba garlic processing 497:522 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 4 40 theme acetic 903:908 arg1 solution 915:922 the acetic acid solution 899:922 the acetic acid solution 899:922 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 1 41 dep Allium 194:199 arg1 L. 209:210 Allium sativum L. 194:210 Allium sativum L. 194:210 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 0 42 theme composition 37:47 arg1 analysis 49:56 the composition analysis 33:56 the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS 33:140 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 0 43 theme Q-TOF 127:131 arg1 LC-MS/MS 133:140 Q-TOF LC-MS/MS 127:140 Q-TOF LC-MS/MS 127:140 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 2 44 theme spatial 427:433 arg1 changes 448:454 the garlic tissue spatial distribution changes 409:454 the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing 409:522 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 45 theme mass 322:325 arg1 spectrometry 327:338 matrix-assisted laser desorption/ionization imaging mass spectrometry 270:338 matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) 270:354 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 45 theme mass 322:325 arg1 MSI 351:353 MALDI-TOF MSI 341:353 MALDI-TOF MSI 341:353 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 5 46 theme spatial 1031:1037 arg1 distributions 1039:1051 the spatial distributions 1027:1051 the spatial distributions 1027:1051 This study provided a basis for the spatial distributions and changes of compounds in garlic tissue during Laba garlic processing, which suggested that the bioactivities of garlic might be changed after processing owing to the transformation and change of the constituents. 37120200 1 47 with product 213:219 arg1 effects 242:248 multiple health effects 226:248 multiple health effects 226:248 Laba garlic is a kind of vinegar processed garlic (Allium sativum L.) product with multiple health effects. 37120200 2 48 theme imaging 314:320 arg1 spectrometry 327:338 matrix-assisted laser desorption/ionization imaging mass spectrometry 270:338 matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) 270:354 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 48 theme imaging 314:320 arg1 MSI 351:353 MALDI-TOF MSI 341:353 MALDI-TOF MSI 341:353 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 4 49 theme acid 910:913 arg1 solution 915:922 the acetic acid solution 899:922 the acetic acid solution 899:922 During Laba garlic processing, some bioactive compounds such as alliin and saponins were lost because they were transformed into other compounds or leached into the acetic acid solution, and some new compounds including pigments-related compounds occurred. 37120200 5 50 theme compounds 1068:1076 arg1 basis 1017:1021 a basis 1015:1021 a basis for the spatial distributions 1015:1051 This study provided a basis for the spatial distributions and changes of compounds in garlic tissue during Laba garlic processing, which suggested that the bioactivities of garlic might be changed after processing owing to the transformation and change of the constituents. 37120200 5 50 theme compounds 1068:1076 arg1 changes 1057:1063 changes 1057:1063 changes of compounds 1057:1076 This study provided a basis for the spatial distributions and changes of compounds in garlic tissue during Laba garlic processing, which suggested that the bioactivities of garlic might be changed after processing owing to the transformation and change of the constituents. 37120200 2 51 theme desorption/ionization 292:312 arg1 spectrometry 327:338 matrix-assisted laser desorption/ionization imaging mass spectrometry 270:338 matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) 270:354 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 51 theme desorption/ionization 292:312 arg1 MSI 351:353 MALDI-TOF MSI 341:353 MALDI-TOF MSI 341:353 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 0 52 theme processed 61:69 arg1 garlic 71:76 processed garlic 61:76 processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS 61:140 A novel visualization method for the composition analysis of processed garlic by MALDI-TOF imaging mass spectrometry (MSI) and Q-TOF LC-MS/MS. 37120200 3 53 theme organosulfur 664:675 arg1 compounds 677:685 organosulfur compounds 664:685 organosulfur compounds 664:685 The distribution characteristics of the compounds were observed in processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins. 37120200 2 54 theme weight 473:478 arg1 compounds 480:488 low molecular weight compounds 459:488 low molecular weight compounds 459:488 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 5 55 theme garlic 1168:1173 arg1 bioactivities 1151:1163 the bioactivities 1147:1163 the bioactivities of garlic 1147:1173 This study provided a basis for the spatial distributions and changes of compounds in garlic tissue during Laba garlic processing, which suggested that the bioactivities of garlic might be changed after processing owing to the transformation and change of the constituents. 37120200 3 56 theme unprocessed 606:616 arg1 garlic 618:623 processed and unprocessed garlic 592:623 processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins 592:735 The distribution characteristics of the compounds were observed in processed and unprocessed garlic including amino acids and derivatives, organosulfur compounds, pigment precursors, polysaccharides and saponins. 37120200 2 57 theme tissue 420:425 arg1 changes 448:454 the garlic tissue spatial distribution changes 409:454 the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing 409:522 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 37120200 2 58 theme Laba 501:504 arg1 processing 513:522 the Laba garlic processing 497:522 the Laba garlic processing 497:522 This study applied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-TOF MSI) and Q-TOF LC-MS/MS for the first time to investigate the garlic tissue spatial distribution changes of low molecular weight compounds during the Laba garlic processing. 35500775 0 0 theme diabetic 75:82 arg1 healing 90:96 diabetic wound healing 75:96 diabetic wound healing 75:96 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 3 1 theme molecular 678:686 arg1 weight 688:693 molecular weight 678:693 molecular weight 678:693 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 35500775 2 2 theme G-100 578:582 arg1 gel 584:586 Sephadex G-100 gel 569:586 Sephadex G-100 gel in succession 569:600 Herein, we innovatively isolated two glycoproteins from PA, named PAGP-1 and PAGP-2, which were obtained by Cellulose DE-52 chromatography and purified by Sephadex G-100 gel in succession. 35500775 6 3 theme diabetic 1260:1267 arg1 mice 1269:1272 diabetic mice 1260:1272 diabetic mice 1260:1272 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 1 4 theme increasing 153:162 arg1 attempts 164:171 the increasing attempts 149:171 the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine 149:308 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 6 5 theme macrophages 1407:1417 arg1 polarization 1391:1402 the polarization 1387:1402 the polarization of macrophages M1 to M2 1387:1426 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 4 6 theme O-glycopeptide 863:876 arg1 bonds 878:882 O-glycopeptide bonds 863:882 O-glycopeptide bonds linked glycoproteins 863:903 As a result, two PAGPs belonged to O-glycopeptide bonds linked glycoproteins. 35500775 7 7 theme bioactive 1534:1542 arg1 substances 1544:1553 the potential wound healing bioactive substances 1506:1553 the potential wound healing bioactive substances in PA 1506:1559 In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. 35500775 7 7 theme bioactive 1534:1542 arg1 glycoproteins 1483:1495 the glycoproteins 1479:1495 the glycoproteins 1479:1495 In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. 35500775 2 8 theme Sephadex 569:576 arg1 gel 584:586 Sephadex G-100 gel 569:586 Sephadex G-100 gel in succession 569:600 Herein, we innovatively isolated two glycoproteins from PA, named PAGP-1 and PAGP-2, which were obtained by Cellulose DE-52 chromatography and purified by Sephadex G-100 gel in succession. 35500775 7 9 theme clear 1459:1463 arg1 evidence 1465:1472 clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA 1459:1559 clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA 1459:1559 In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. 35500775 2 10 from PA 470:471 arg1 glycoproteins 451:463 two glycoproteins 447:463 two glycoproteins 447:463 Herein, we innovatively isolated two glycoproteins from PA, named PAGP-1 and PAGP-2, which were obtained by Cellulose DE-52 chromatography and purified by Sephadex G-100 gel in succession. 35500775 1 11 from insect 271:276 arg1 medicine 301:308 traditional Chinese medicine 281:308 traditional Chinese medicine 281:308 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 5 12 theme carbohydrate 921:932 arg1 content 910:916 The content 906:916 The content of carbohydrate and protein of PAGP-1 906:954 The content of carbohydrate and protein of PAGP-1 was approximately 25.23% and 65.92% respectively, which of PAGP-2 was approximately 25.71% and 71.23%. 35500775 5 12 theme carbohydrate 921:932 arg1 % 979:979 approximately 25.23% 960:979 approximately 25.23% 960:979 The content of carbohydrate and protein of PAGP-1 was approximately 25.23% and 65.92% respectively, which of PAGP-2 was approximately 25.71% and 71.23%. 35500775 0 13 theme wound 84:88 arg1 healing 90:96 diabetic wound healing 75:96 diabetic wound healing 75:96 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 3 14 theme amino 696:700 arg1 acid 702:705 amino acid 696:705 amino acid 696:705 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 35500775 6 15 theme full-thickness 1228:1241 arg1 healing 1249:1255 full-thickness wound healing 1228:1255 full-thickness wound healing in diabetic mice 1228:1272 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 7 16 gly glycoproteins 1483:1495 arg1 glycoproteins 1483:1495 the glycoproteins 1479:1495 the glycoproteins 1479:1495 In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. 35500775 7 16 gly glycoproteins 1483:1495 arg1 substances 1544:1553 the potential wound healing bioactive substances 1506:1553 the potential wound healing bioactive substances in PA 1506:1559 In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. 35500775 6 17 theme LPS-induced 1121:1131 arg1 cells 1142:1146 LPS-induced RAW264.7 cells 1121:1146 LPS-induced RAW264.7 cells 1121:1146 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 3 18 theme CD 787:788 arg1 spectroscopy 790:801 CD spectroscopy 787:801 CD spectroscopy 787:801 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 35500775 0 19 theme macrophage 102:111 arg1 modulation 126:135 macrophage polarization modulation 102:135 macrophage polarization modulation 102:135 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 0 20 from americana 52:60 arg1 glycoproteins 4:16 Two glycoproteins 0:16 Two glycoproteins from medicinal insect Periplaneta americana (L.) 0:65 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 6 21 dep type 1338:1341 arg1 fibers 1367:1372 collagen fibers 1358:1372 collagen fibers 1358:1372 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 5 22 theme protein 938:944 arg1 content 910:916 The content 906:916 The content of carbohydrate and protein of PAGP-1 906:954 The content of carbohydrate and protein of PAGP-1 was approximately 25.23% and 65.92% respectively, which of PAGP-2 was approximately 25.71% and 71.23%. 35500775 5 22 theme protein 938:944 arg1 % 979:979 approximately 25.23% 960:979 approximately 25.23% 960:979 The content of carbohydrate and protein of PAGP-1 was approximately 25.23% and 65.92% respectively, which of PAGP-2 was approximately 25.71% and 71.23%. 35500775 6 23 theme type 1338:1341 arg1 ratio 1329:1333 the ratio 1325:1333 the ratio of type I and type III collagen fibers 1325:1372 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 7 24 from substances 1544:1553 arg1 PA 1558:1559 PA 1558:1559 PA 1558:1559 In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. 35500775 6 25 theme PAGPs 1112:1116 arg1 effects 1101:1107 the remarkable anti-inflammatory effects 1068:1107 the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells 1068:1146 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 3 26 theme morphology 739:748 arg1 analysis 750:757 morphology analysis 739:757 morphology analysis 739:757 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 35500775 3 27 theme monosaccharide 711:724 arg1 composition 726:736 monosaccharide composition 711:736 monosaccharide composition 711:736 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 35500775 6 28 theme PAGP-1 1179:1184 arg1 administration 1161:1174 the topical administration 1149:1174 the topical administration of PAGP-1 and PAGP-2 1149:1195 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 3 29 dep analysis 750:757 arg1 linkage 819:825 linkage 819:825 linkage 819:825 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 35500775 5 30 dep % 979:979 arg1 % 1045:1045 approximately 25.71% 1026:1045 approximately 25.71% 1026:1045 The content of carbohydrate and protein of PAGP-1 was approximately 25.23% and 65.92% respectively, which of PAGP-2 was approximately 25.71% and 71.23%. 35500775 5 30 dep % 979:979 arg1 % 1056:1056 71.23% 1051:1056 71.23% 1051:1056 The content of carbohydrate and protein of PAGP-1 was approximately 25.23% and 65.92% respectively, which of PAGP-2 was approximately 25.71% and 71.23%. 35500775 6 31 theme PAGP-2 1190:1195 arg1 administration 1161:1174 the topical administration 1149:1174 the topical administration of PAGP-1 and PAGP-2 1149:1195 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 1 32 theme wound 188:192 arg1 healing 194:200 wound healing 188:200 wound healing 188:200 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 0 33 theme medicinal 23:31 arg1 L. 63:64 L. 63:64 L. 63:64 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 0 33 theme medicinal 23:31 arg1 americana 52:60 medicinal insect Periplaneta americana 23:60 medicinal insect Periplaneta americana (L.) 23:65 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 4 34 theme bonds 878:882 arg1 glycoproteins 891:903 O-glycopeptide bonds linked glycoproteins 863:903 O-glycopeptide bonds linked glycoproteins 863:903 As a result, two PAGPs belonged to O-glycopeptide bonds linked glycoproteins. 35500775 6 35 theme anti-inflammatory 1083:1099 arg1 effects 1101:1107 the remarkable anti-inflammatory effects 1068:1107 the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells 1068:1146 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 7 36 theme wound 1520:1524 arg1 healing 1526:1532 the potential wound healing 1506:1532 the potential wound healing bioactive substances in PA 1506:1559 In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. 35500775 0 37 theme polarization 113:124 arg1 modulation 126:135 macrophage polarization modulation 102:135 macrophage polarization modulation 102:135 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 1 38 theme endogenetic 348:358 arg1 polysaccharides 384:398 polysaccharides 384:398 polysaccharides 384:398 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 1 38 theme endogenetic 348:358 arg1 macromolecules 360:373 the endogenetic macromolecules 344:373 the endogenetic macromolecules 344:373 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 1 38 theme endogenetic 348:358 arg1 peptides 404:411 peptides 404:411 peptides 404:411 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 6 39 theme remarkable 1072:1081 arg1 effects 1101:1107 the remarkable anti-inflammatory effects 1068:1107 the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells 1068:1146 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 1 40 theme effective 202:210 arg1 substances 212:221 the wound healing effective substances 184:221 the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine 184:308 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 0 41 theme Periplaneta 40:50 arg1 L. 63:64 L. 63:64 L. 63:64 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 0 41 theme Periplaneta 40:50 arg1 americana 52:60 medicinal insect Periplaneta americana 23:60 medicinal insect Periplaneta americana (L.) 23:65 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 1 42 theme medicinal 261:269 arg1 americana 238:246 Periplaneta americana 226:246 Periplaneta americana (L.) (PA) 226:256 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 1 42 theme medicinal 261:269 arg1 insect 271:276 a medicinal insect 259:276 a medicinal insect in traditional Chinese medicine 259:308 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 6 43 theme collagen 1358:1365 arg1 fibers 1367:1372 collagen fibers 1358:1372 collagen fibers 1358:1372 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 6 44 from effects 1101:1107 arg1 cells 1142:1146 LPS-induced RAW264.7 cells 1121:1146 LPS-induced RAW264.7 cells 1121:1146 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 0 45 theme insect 33:38 arg1 L. 63:64 L. 63:64 L. 63:64 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 0 45 theme insect 33:38 arg1 americana 52:60 medicinal insect Periplaneta americana 23:60 medicinal insect Periplaneta americana (L.) 23:65 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 6 46 dep macrophages 1407:1417 arg1 M1 1419:1420 M1 1419:1420 macrophages M1 to M2 1407:1426 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 4 47 theme linked 884:889 arg1 glycoproteins 891:903 O-glycopeptide bonds linked glycoproteins 863:903 O-glycopeptide bonds linked glycoproteins 863:903 As a result, two PAGPs belonged to O-glycopeptide bonds linked glycoproteins. 35500775 0 48 gly glycoproteins 4:16 arg1 glycoproteins 4:16 Two glycoproteins 0:16 Two glycoproteins from medicinal insect Periplaneta americana (L.) 0:65 Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. 35500775 7 49 theme healing 1526:1532 arg1 substances 1544:1553 the potential wound healing bioactive substances 1506:1553 the potential wound healing bioactive substances in PA 1506:1559 In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. 35500775 7 49 theme healing 1526:1532 arg1 glycoproteins 1483:1495 the glycoproteins 1479:1495 the glycoproteins 1479:1495 In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. 35500775 2 50 from gel 584:586 arg1 succession 591:600 succession 591:600 succession 591:600 Herein, we innovatively isolated two glycoproteins from PA, named PAGP-1 and PAGP-2, which were obtained by Cellulose DE-52 chromatography and purified by Sephadex G-100 gel in succession. 35500775 3 51 theme structural 607:616 arg1 characterization 618:633 The structural characterization 603:633 The structural characterization of the two PAGPs 603:650 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 35500775 4 52 gly O-glycopeptide 863:876 arg2 O-glycopeptide 863:876 O-glycopeptide bonds 863:882 O-glycopeptide bonds linked glycoproteins 863:903 As a result, two PAGPs belonged to O-glycopeptide bonds linked glycoproteins. 35500775 6 53 theme type 1349:1352 arg1 ratio 1329:1333 the ratio 1325:1333 the ratio of type I and type III collagen fibers 1325:1372 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 1 54 theme traditional 281:291 arg1 medicine 301:308 traditional Chinese medicine 281:308 traditional Chinese medicine 281:308 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 3 55 theme PAGPs 646:650 arg1 characterization 618:633 The structural characterization 603:633 The structural characterization of the two PAGPs 603:650 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 35500775 6 56 dep M1 1419:1420 arg1 M2 1425:1426 M2 1425:1426 macrophages M1 to M2 1407:1426 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 6 56 dep M1 1419:1420 arg1 to 1422:1423 to 1422:1423 to 1422:1423 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 6 57 theme wound 1243:1247 arg1 healing 1249:1255 full-thickness wound healing 1228:1255 full-thickness wound healing in diabetic mice 1228:1272 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 1 58 theme Chinese 293:299 arg1 medicine 301:308 traditional Chinese medicine 281:308 traditional Chinese medicine 281:308 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 2 59 theme DE-52 532:536 arg1 chromatography 538:551 Cellulose DE-52 chromatography 522:551 Cellulose DE-52 chromatography 522:551 Herein, we innovatively isolated two glycoproteins from PA, named PAGP-1 and PAGP-2, which were obtained by Cellulose DE-52 chromatography and purified by Sephadex G-100 gel in succession. 35500775 6 60 theme topical 1153:1159 arg1 administration 1161:1174 the topical administration 1149:1174 the topical administration of PAGP-1 and PAGP-2 1149:1195 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 5 61 theme PAGP-1 949:954 arg1 protein 938:944 protein 938:944 protein 938:944 The content of carbohydrate and protein of PAGP-1 was approximately 25.23% and 65.92% respectively, which of PAGP-2 was approximately 25.71% and 71.23%. 35500775 5 61 theme PAGP-1 949:954 arg1 carbohydrate 921:932 carbohydrate 921:932 carbohydrate 921:932 The content of carbohydrate and protein of PAGP-1 was approximately 25.23% and 65.92% respectively, which of PAGP-2 was approximately 25.71% and 71.23%. 35500775 2 62 gly glycoproteins 451:463 arg1 glycoproteins 451:463 two glycoproteins 447:463 two glycoproteins 447:463 Herein, we innovatively isolated two glycoproteins from PA, named PAGP-1 and PAGP-2, which were obtained by Cellulose DE-52 chromatography and purified by Sephadex G-100 gel in succession. 35500775 1 63 theme Periplaneta 226:236 arg1 L 249:249 L. 249:250 L. 249:250 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 1 63 theme Periplaneta 226:236 arg1 americana 238:246 Periplaneta americana 226:246 Periplaneta americana (L.) (PA) 226:256 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 1 63 theme Periplaneta 226:236 arg1 insect 271:276 a medicinal insect 259:276 a medicinal insect in traditional Chinese medicine 259:308 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 1 63 theme Periplaneta 226:236 arg1 PA 254:255 PA 254:255 PA 254:255 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 2 64 theme Cellulose 522:530 arg1 chromatography 538:551 Cellulose DE-52 chromatography 522:551 Cellulose DE-52 chromatography 522:551 Herein, we innovatively isolated two glycoproteins from PA, named PAGP-1 and PAGP-2, which were obtained by Cellulose DE-52 chromatography and purified by Sephadex G-100 gel in succession. 35500775 6 65 theme RAW264.7 1133:1140 arg1 cells 1142:1146 LPS-induced RAW264.7 cells 1121:1146 LPS-induced RAW264.7 cells 1121:1146 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 4 66 gly glycoproteins 891:903 arg1 glycoproteins 891:903 O-glycopeptide bonds linked glycoproteins 863:903 O-glycopeptide bonds linked glycoproteins 863:903 As a result, two PAGPs belonged to O-glycopeptide bonds linked glycoproteins. 35500775 1 67 theme americana 238:246 arg1 substances 212:221 the wound healing effective substances 184:221 the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine 184:308 Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. 35500775 7 68 theme potential 1510:1518 arg1 healing 1526:1532 the potential wound healing 1506:1532 the potential wound healing bioactive substances in PA 1506:1559 In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. 35500775 6 69 from healing 1249:1255 arg1 mice 1269:1272 diabetic mice 1260:1272 diabetic mice 1260:1272 Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. 35500775 4 70 link linked 884:889 arg1 glycoproteins 891:903 O-glycopeptide bonds linked glycoproteins 863:903 O-glycopeptide bonds linked glycoproteins 863:903 As a result, two PAGPs belonged to O-glycopeptide bonds linked glycoproteins. 35500775 3 71 theme 1H 770:771 arg1 analysis 777:784 FT-IR and 1H NMR analysis 760:784 analysis 777:784 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 35500775 3 72 theme NMR 773:775 arg1 analysis 777:784 FT-IR and 1H NMR analysis 760:784 analysis 777:784 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 35500775 3 73 theme FT-IR 760:764 arg1 analysis 777:784 FT-IR and 1H NMR analysis 760:784 analysis 777:784 The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. 37334351 5 0 gly glycoprotein 734:745 arg1 glycoprotein 734:745 The resulting Candid#1 glycoprotein complex 711:753 The resulting Candid#1 glycoprotein complex 711:753 The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. 37334351 6 1 theme recombinant 947:957 arg1 viruses 959:965 recombinant viruses 947:965 recombinant viruses expressing GPC mutations specific to key Candid#1 passages 947:1024 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 2 2 theme live 294:297 arg1 # 346:346 Candid#1 340:347 called Candid#1 333:347 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 2 2 theme live 294:297 arg1 vaccine 310:316 A live attenuated vaccine 292:316 A live attenuated vaccine for human use 292:330 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 2 2 theme live 294:297 arg1 approved 353:360 approved 353:360 approved 353:360 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 9 3 theme strain 1736:1741 arg1 attenuation 1676:1686 complete attenuation 1667:1686 complete attenuation 1667:1686 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 9 3 theme strain 1736:1741 arg1 immunogenicity 1701:1714 enhanced immunogenicity 1692:1714 enhanced immunogenicity of Candid#1 vaccine strain 1692:1741 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 3 4 theme Junin 408:412 arg1 virus 414:418 Junin virus 408:418 Junin virus 408:418 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 9 5 gly glycosylation 1561:1573 arg2 motif 1575:1579 an N-linked glycosylation motif 1549:1579 an N-linked glycosylation motif 1549:1579 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 1 6 theme Argentine 212:220 arg1 disease 262:268 a potentially lethal disease 241:268 a potentially lethal disease endemic to Argentina 241:289 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 1 6 theme Argentine 212:220 arg1 fever 234:238 Argentine hemorrhagic fever 212:238 Argentine hemorrhagic fever 212:238 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 10 7 theme glycosylation 1774:1786 arg1 targets 1851:1857 viable targets 1844:1857 viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses 1844:1961 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 10 7 theme glycosylation 1774:1786 arg1 profiles 1788:1795 The highly conserved N-linked glycosylation profiles 1744:1795 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins 1744:1823 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 6 8 theme hemorrhagic 1113:1123 arg1 fever 1125:1129 Argentine hemorrhagic fever 1103:1129 Argentine hemorrhagic fever 1103:1129 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 3 9 theme serial 441:446 arg1 passage 448:454 serial passage 441:454 serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells 441:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 5 10 theme glycoprotein 734:745 arg1 complex 747:753 The resulting Candid#1 glycoprotein complex 711:753 The resulting Candid#1 glycoprotein complex 711:753 The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. 37334351 9 11 theme N-linked 1552:1559 arg1 motif 1575:1579 an N-linked glycosylation motif 1549:1579 an N-linked glycosylation motif 1549:1579 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 6 12 theme Hartley 1075:1081 arg1 model 1094:1098 our outbred Hartley guinea pig model 1063:1098 our outbred Hartley guinea pig model 1063:1098 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 6 13 theme Candid 1008:1013 arg1 # 1014:1014 Candid#1 1008:1015 key Candid#1 passages 1004:1024 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 10 14 theme glycoproteins 1811:1823 arg1 targets 1851:1857 viable targets 1844:1857 viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses 1844:1961 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 10 14 theme glycoproteins 1811:1823 arg1 profiles 1788:1795 The highly conserved N-linked glycosylation profiles 1744:1795 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins 1744:1823 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 3 15 theme brain 465:469 arg1 tissues 471:477 mouse brain tissues 459:477 mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells 459:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 5 16 theme resulting 715:723 arg1 complex 747:753 The resulting Candid#1 glycoprotein complex 711:753 The resulting Candid#1 glycoprotein complex 711:753 The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. 37334351 3 17 theme Fetal 502:506 arg1 cells 546:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 5 18 theme # 731:731 arg1 complex 747:753 The resulting Candid#1 glycoprotein complex 711:753 The resulting Candid#1 glycoprotein complex 711:753 The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. 37334351 6 19 theme guinea 1083:1088 arg1 model 1094:1098 our outbred Hartley guinea pig model 1063:1098 our outbred Hartley guinea pig model 1063:1098 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 10 20 theme viable 1844:1849 arg1 profiles 1788:1795 The highly conserved N-linked glycosylation profiles 1744:1795 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins 1744:1823 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 10 20 theme viable 1844:1849 arg1 targets 1851:1857 viable targets 1844:1857 viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses 1844:1961 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 5 21 theme reticulum 791:799 arg1 stress 806:811 endoplasmic reticulum (ER) stress 779:811 endoplasmic reticulum (ER) stress 779:811 The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. 37334351 8 22 theme 13th 1336:1339 arg1 XJ13 1362:1365 XJ13 1362:1365 XJ13 1362:1365 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 8 22 theme 13th 1336:1339 arg1 passage 1353:1359 the 13th mouse brain passage 1332:1359 the 13th mouse brain passage (XJ13) 1332:1366 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 6 23 theme outbred 1067:1073 arg1 model 1094:1098 our outbred Hartley guinea pig model 1063:1098 our outbred Hartley guinea pig model 1063:1098 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 3 24 theme fibroblast 528:537 arg1 cells 546:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 10 25 gly glycosylation 1774:1786 arg1 glycoproteins 1811:1823 arenavirus glycoproteins 1800:1823 arenavirus glycoproteins 1800:1823 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 9 26 theme 44th 1604:1607 arg1 XJ44 1630:1633 XJ44 1630:1633 XJ44 1630:1633 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 9 26 theme 44th 1604:1607 arg1 passage 1621:1627 the 44th mouse brain passage 1600:1627 the 44th mouse brain passage (XJ44) 1600:1634 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 8 27 theme brain 1347:1351 arg1 XJ13 1362:1365 XJ13 1362:1365 XJ13 1362:1365 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 8 27 theme brain 1347:1351 arg1 passage 1353:1359 the 13th mouse brain passage 1332:1359 the 13th mouse brain passage (XJ13) 1332:1366 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 4 28 theme responsible 579:589 arg1 mutations 569:577 the mutations 565:577 the mutations responsible for attenuation of this virus in Guinea pigs 565:634 Previously, the mutations responsible for attenuation of this virus in Guinea pigs were mapped in the gene encoding for glycoprotein precursor (GPC) protein. 37334351 10 29 theme attenuating 1873:1883 arg1 viruses 1885:1891 attenuating viruses 1873:1891 attenuating viruses for vaccine development against other arenavirus-associated illnesses 1873:1961 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 3 30 theme macaque 515:521 arg1 cells 546:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 9 31 theme brain 1615:1619 arg1 XJ44 1630:1633 XJ44 1630:1633 XJ44 1630:1633 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 9 31 theme brain 1615:1619 arg1 passage 1621:1627 the 44th mouse brain passage 1600:1627 the 44th mouse brain passage (XJ44) 1600:1634 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 6 32 from pathogenicity 1046:1058 arg1 model 1094:1098 our outbred Hartley guinea pig model 1063:1098 our outbred Hartley guinea pig model 1063:1098 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 10 33 theme other 1925:1929 arg1 illnesses 1953:1961 other arenavirus-associated illnesses 1925:1961 other arenavirus-associated illnesses 1925:1961 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 0 34 theme # 64:64 arg1 GPC 67:69 the Candid #1 GPC 53:69 the Candid #1 GPC 53:69 The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation. 37334351 2 35 from Argentina 370:378 arg1 vaccine 310:316 A live attenuated vaccine 292:316 A live attenuated vaccine for human use 292:330 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 2 35 from Argentina 370:378 arg1 approved 353:360 approved 353:360 approved 353:360 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 7 36 theme early 1163:1167 arg1 mutations 1169:1177 early mutations 1163:1177 early mutations in GPC obtained through serial passaging 1163:1218 Here, we provide evidence that early mutations in GPC obtained through serial passaging attenuate the visceral disease and increase immunogenicity in guinea pigs. 37334351 2 37 theme called 333:338 arg1 # 346:346 Candid#1 340:347 called Candid#1 333:347 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 2 37 theme called 333:338 arg1 vaccine 310:316 A live attenuated vaccine 292:316 A live attenuated vaccine for human use 292:330 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 0 38 theme Junin 74:78 arg1 attenuation 86:96 Junin virus attenuation 74:96 Junin virus attenuation 74:96 The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation. 37334351 1 39 theme hemorrhagic 222:232 arg1 disease 262:268 a potentially lethal disease 241:268 a potentially lethal disease endemic to Argentina 241:289 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 1 39 theme hemorrhagic 222:232 arg1 fever 234:238 Argentine hemorrhagic fever 212:238 Argentine hemorrhagic fever 212:238 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 3 40 from passage 491:497 arg1 cells 546:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 3 41 theme Candid 381:386 arg1 strain 398:403 Candid#1 vaccine strain 381:403 Candid#1 vaccine strain of Junin virus 381:418 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 10 42 gly glycoproteins 1811:1823 arg1 glycoproteins 1811:1823 arenavirus glycoproteins 1800:1823 arenavirus glycoproteins 1800:1823 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 6 43 theme specific 905:912 arg1 mutations 914:922 specific mutations 905:922 specific mutations within GPC 905:933 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 8 44 theme disease 1416:1422 arg1 attenuation 1388:1398 attenuation 1388:1398 attenuation of the visceral disease 1388:1422 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 4 45 gly glycoprotein 673:684 arg1 glycoprotein 673:684 glycoprotein precursor (GPC) protein 673:708 glycoprotein precursor (GPC) protein 673:708 Previously, the mutations responsible for attenuation of this virus in Guinea pigs were mapped in the gene encoding for glycoprotein precursor (GPC) protein. 37334351 3 46 theme FRhL 540:543 arg1 cells 546:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 0 47 theme mutations 36:44 arg1 roles 4:8 The roles 0:8 The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation. 0:97 The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation. 37334351 8 48 from impact 1440:1445 arg1 neurovirulence 1454:1467 the neurovirulence 1450:1467 the neurovirulence of Junin virus 1450:1482 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 6 49 theme specific 992:999 arg1 mutations 982:990 GPC mutations 978:990 GPC mutations specific to key Candid#1 passages 978:1024 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 9 50 theme enhanced 1692:1699 arg1 immunogenicity 1701:1714 enhanced immunogenicity 1692:1714 enhanced immunogenicity of Candid#1 vaccine strain 1692:1741 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 9 51 link N-linked 1552:1559 arg1 motif 1575:1579 an N-linked glycosylation motif 1549:1579 an N-linked glycosylation motif 1549:1579 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 4 52 theme glycoprotein 673:684 arg1 protein 702:708 glycoprotein precursor (GPC) protein 673:708 glycoprotein precursor (GPC) protein 673:708 Previously, the mutations responsible for attenuation of this virus in Guinea pigs were mapped in the gene encoding for glycoprotein precursor (GPC) protein. 37334351 7 53 from mutations 1169:1177 arg1 GPC 1182:1184 GPC 1182:1184 GPC obtained through serial passaging 1182:1218 Here, we provide evidence that early mutations in GPC obtained through serial passaging attenuate the visceral disease and increase immunogenicity in guinea pigs. 37334351 6 54 theme GPC 978:980 arg1 mutations 982:990 GPC mutations 978:990 GPC mutations specific to key Candid#1 passages 978:1024 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 9 55 theme # 1725:1725 arg1 strain 1736:1741 Candid#1 vaccine strain 1719:1741 Candid#1 vaccine strain 1719:1741 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 2 56 theme attenuated 299:308 arg1 # 346:346 Candid#1 340:347 called Candid#1 333:347 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 2 56 theme attenuated 299:308 arg1 vaccine 310:316 A live attenuated vaccine 292:316 A live attenuated vaccine for human use 292:330 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 2 56 theme attenuated 299:308 arg1 approved 353:360 approved 353:360 approved 353:360 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 1 57 theme responsible 188:198 arg1 pathogen 179:186 the pathogen 175:186 the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina 175:289 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 9 58 theme vaccine 1728:1734 arg1 strain 1736:1741 Candid#1 vaccine strain 1719:1741 Candid#1 vaccine strain 1719:1741 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 8 59 theme virus 1478:1482 arg1 neurovirulence 1454:1467 the neurovirulence 1450:1467 the neurovirulence of Junin virus 1450:1482 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 6 60 theme fever 1125:1129 arg1 pathogenicity 1046:1058 their pathogenicity 1040:1058 their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever 1040:1129 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 10 61 theme N-linked 1765:1772 arg1 targets 1851:1857 viable targets 1844:1857 viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses 1844:1961 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 10 61 theme N-linked 1765:1772 arg1 profiles 1788:1795 The highly conserved N-linked glycosylation profiles 1744:1795 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins 1744:1823 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 6 62 theme Argentine 1103:1111 arg1 fever 1125:1129 Argentine hemorrhagic fever 1103:1129 Argentine hemorrhagic fever 1103:1129 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 6 63 theme # 1014:1014 arg1 passages 1017:1024 key Candid#1 passages 1004:1024 key Candid#1 passages 1004:1024 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 3 64 theme mouse 459:463 arg1 tissues 471:477 mouse brain tissues 459:477 mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells 459:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 1 65 theme Arenaviridae 137:148 arg1 family 150:155 the Arenaviridae family 133:155 the Arenaviridae family of viruses 133:166 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 7 66 theme guinea 1282:1287 arg1 pigs 1289:1292 guinea pigs 1282:1292 guinea pigs 1282:1292 Here, we provide evidence that early mutations in GPC obtained through serial passaging attenuate the visceral disease and increase immunogenicity in guinea pigs. 37334351 9 67 theme glycosylation 1561:1573 arg1 motif 1575:1579 an N-linked glycosylation motif 1549:1579 an N-linked glycosylation motif 1549:1579 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 6 68 theme key 1004:1006 arg1 passages 1017:1024 key Candid#1 passages 1004:1024 key Candid#1 passages 1004:1024 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 10 69 theme arenavirus 1800:1809 arg1 glycoproteins 1811:1823 arenavirus glycoproteins 1800:1823 arenavirus glycoproteins 1800:1823 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 5 70 theme Candid 725:730 arg1 complex 747:753 The resulting Candid#1 glycoprotein complex 711:753 The resulting Candid#1 glycoprotein complex 711:753 The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. 37334351 6 71 theme pig 1090:1092 arg1 model 1094:1098 our outbred Hartley guinea pig model 1063:1098 our outbred Hartley guinea pig model 1063:1098 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 1 72 theme endemic 270:276 arg1 disease 262:268 a potentially lethal disease 241:268 a potentially lethal disease endemic to Argentina 241:289 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 1 72 theme endemic 270:276 arg1 fever 234:238 Argentine hemorrhagic fever 212:238 Argentine hemorrhagic fever 212:238 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 5 73 theme endoplasmic 779:789 arg1 reticulum 791:799 endoplasmic reticulum 779:799 endoplasmic reticulum (ER) stress 779:811 The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. 37334351 5 73 theme endoplasmic 779:789 arg1 ER 802:803 ER 802:803 ER 802:803 The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. 37334351 8 74 theme mouse 1341:1345 arg1 XJ13 1362:1365 XJ13 1362:1365 XJ13 1362:1365 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 8 74 theme mouse 1341:1345 arg1 passage 1353:1359 the 13th mouse brain passage 1332:1359 the 13th mouse brain passage (XJ13) 1332:1366 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 7 75 theme visceral 1234:1241 arg1 disease 1243:1249 the visceral disease 1230:1249 the visceral disease 1230:1249 Here, we provide evidence that early mutations in GPC obtained through serial passaging attenuate the visceral disease and increase immunogenicity in guinea pigs. 37334351 3 76 theme lung 523:526 arg1 cells 546:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 1 77 theme Junin 99:103 arg1 JUNV 112:115 JUNV 112:115 JUNV 112:115 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 1 77 theme Junin 99:103 arg1 virus 105:109 Junin virus 99:109 Junin virus (JUNV) 99:116 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 1 77 theme Junin 99:103 arg1 member 123:128 a member 121:128 a member of the Arenaviridae family of viruses 121:166 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 7 78 from immunogenicity 1264:1277 arg1 pigs 1289:1292 guinea pigs 1282:1292 guinea pigs 1282:1292 Here, we provide evidence that early mutations in GPC obtained through serial passaging attenuate the visceral disease and increase immunogenicity in guinea pigs. 37334351 6 79 theme attenuating 879:889 arg1 properties 891:900 the attenuating properties 875:900 the attenuating properties of specific mutations within GPC 875:933 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 4 80 theme virus 615:619 arg1 attenuation 595:605 attenuation 595:605 attenuation of this virus in Guinea pigs 595:634 Previously, the mutations responsible for attenuation of this virus in Guinea pigs were mapped in the gene encoding for glycoprotein precursor (GPC) protein. 37334351 0 81 theme Candid 57:62 arg1 GPC 67:69 the Candid #1 GPC 53:69 the Candid #1 GPC 53:69 The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation. 37334351 3 82 theme Rhesus 508:513 arg1 cells 546:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Fetal Rhesus macaque lung fibroblast (FRhL) cells 502:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 9 83 theme mouse 1609:1613 arg1 XJ44 1630:1633 XJ44 1630:1633 XJ44 1630:1633 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 9 83 theme mouse 1609:1613 arg1 passage 1621:1627 the 44th mouse brain passage 1600:1627 the 44th mouse brain passage (XJ44) 1600:1634 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 2 84 from approved 353:360 arg1 Argentina 370:378 Argentina 370:378 Argentina 370:378 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 7 85 theme serial 1203:1208 arg1 passaging 1210:1218 serial passaging 1203:1218 serial passaging 1203:1218 Here, we provide evidence that early mutations in GPC obtained through serial passaging attenuate the visceral disease and increase immunogenicity in guinea pigs. 37334351 0 86 from roles 4:8 arg1 attenuation 86:96 Junin virus attenuation 74:96 Junin virus attenuation 74:96 The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation. 37334351 3 87 from passage 448:454 arg1 tissues 471:477 mouse brain tissues 459:477 mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells 459:550 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 10 88 theme vaccine 1897:1903 arg1 development 1905:1915 vaccine development 1897:1915 vaccine development 1897:1915 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 0 89 theme virus 80:84 arg1 attenuation 86:96 Junin virus attenuation 74:96 Junin virus attenuation 74:96 The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation. 37334351 1 90 theme family 150:155 arg1 pathogen 179:186 the pathogen 175:186 the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina 175:289 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 1 90 theme family 150:155 arg1 member 123:128 a member 121:128 a member of the Arenaviridae family of viruses 121:166 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 1 90 theme family 150:155 arg1 virus 105:109 Junin virus 99:109 Junin virus (JUNV) 99:116 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 8 91 theme visceral 1407:1414 arg1 disease 1416:1422 the visceral disease 1403:1422 the visceral disease 1403:1422 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 4 92 theme Guinea 624:629 arg1 pigs 631:634 Guinea pigs 624:634 Guinea pigs 624:634 Previously, the mutations responsible for attenuation of this virus in Guinea pigs were mapped in the gene encoding for glycoprotein precursor (GPC) protein. 37334351 2 93 theme human 322:326 arg1 use 328:330 human use 322:330 human use 322:330 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 0 94 theme XJ13 13:16 arg1 mutations 36:44 XJ13 and XJ44-specific mutations 13:44 XJ13 and XJ44-specific mutations within the Candid #1 GPC 13:69 The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation. 37334351 6 95 theme mutations 914:922 arg1 properties 891:900 the attenuating properties 875:900 the attenuating properties of specific mutations within GPC 875:933 To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. 37334351 3 96 theme # 387:387 arg1 strain 398:403 Candid#1 vaccine strain 381:403 Candid#1 vaccine strain of Junin virus 381:418 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 0 97 theme XJ44-specific 22:34 arg1 mutations 36:44 XJ13 and XJ44-specific mutations 13:44 XJ13 and XJ44-specific mutations within the Candid #1 GPC 13:69 The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation. 37334351 10 98 theme arenavirus-associated 1931:1951 arg1 illnesses 1953:1961 other arenavirus-associated illnesses 1925:1961 other arenavirus-associated illnesses 1925:1961 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 9 99 theme complete 1667:1674 arg1 attenuation 1676:1686 complete attenuation 1667:1686 complete attenuation 1667:1686 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 4 100 theme GPC 697:699 arg1 protein 702:708 glycoprotein precursor (GPC) protein 673:708 glycoprotein precursor (GPC) protein 673:708 Previously, the mutations responsible for attenuation of this virus in Guinea pigs were mapped in the gene encoding for glycoprotein precursor (GPC) protein. 37334351 2 101 theme Candid 340:345 arg1 # 346:346 Candid#1 340:347 called Candid#1 333:347 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 2 101 theme Candid 340:345 arg1 vaccine 310:316 A live attenuated vaccine 292:316 A live attenuated vaccine for human use 292:330 A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. 37334351 1 102 theme lethal 255:260 arg1 disease 262:268 a potentially lethal disease 241:268 a potentially lethal disease endemic to Argentina 241:289 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 1 102 theme lethal 255:260 arg1 fever 234:238 Argentine hemorrhagic fever 212:238 Argentine hemorrhagic fever 212:238 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 3 103 theme virus 414:418 arg1 strain 398:403 Candid#1 vaccine strain 381:403 Candid#1 vaccine strain of Junin virus 381:418 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 4 104 theme precursor 686:694 arg1 protein 702:708 glycoprotein precursor (GPC) protein 673:708 glycoprotein precursor (GPC) protein 673:708 Previously, the mutations responsible for attenuation of this virus in Guinea pigs were mapped in the gene encoding for glycoprotein precursor (GPC) protein. 37334351 3 105 theme vaccine 390:396 arg1 strain 398:403 Candid#1 vaccine strain 381:403 Candid#1 vaccine strain of Junin virus 381:418 Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. 37334351 1 106 theme viruses 160:166 arg1 family 150:155 the Arenaviridae family 133:155 the Arenaviridae family of viruses 133:166 Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. 37334351 5 107 theme GPC 858:860 arg1 degradation 839:849 the degradation 835:849 the degradation of the GPC 835:860 The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. 37334351 9 108 theme Candid 1719:1724 arg1 # 1725:1725 Candid#1 1719:1726 Candid#1 vaccine strain 1719:1741 Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. 37334351 8 109 theme Junin 1472:1476 arg1 virus 1478:1482 Junin virus 1472:1482 Junin virus 1472:1482 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 10 110 theme conserved 1755:1763 arg1 targets 1851:1857 viable targets 1844:1857 viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses 1844:1961 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 10 110 theme conserved 1755:1763 arg1 profiles 1788:1795 The highly conserved N-linked glycosylation profiles 1744:1795 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins 1744:1823 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 8 111 theme Specific 1295:1302 arg1 mutations 1304:1312 Specific mutations 1295:1312 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) 1295:1366 Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. 37334351 10 112 link N-linked 1765:1772 arg1 targets 1851:1857 viable targets 1844:1857 viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses 1844:1961 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 10 112 link N-linked 1765:1772 arg1 profiles 1788:1795 The highly conserved N-linked glycosylation profiles 1744:1795 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins 1744:1823 The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses. 37334351 4 113 from attenuation 595:605 arg1 pigs 631:634 Guinea pigs 624:634 Guinea pigs 624:634 Previously, the mutations responsible for attenuation of this virus in Guinea pigs were mapped in the gene encoding for glycoprotein precursor (GPC) protein. 37265400 9 0 theme spectrometry 1715:1726 arg1 method 1755:1760 a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method 1670:1760 a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method 1670:1760 This work illustrates the utility of applying a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method to support the development of engineered antibody scaffolds. 37265400 4 1 theme disulfide 908:916 arg1 bonds 918:922 interchain disulfide bonds 897:922 interchain disulfide bonds 897:922 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 9 2 theme monitoring 1744:1753 arg1 method 1755:1760 a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method 1670:1760 a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method 1670:1760 This work illustrates the utility of applying a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method to support the development of engineered antibody scaffolds. 37265400 2 3 theme monoclonal 368:377 arg1 antibodies 379:388 monoclonal antibodies 368:388 monoclonal antibodies 368:388 Among the numerous strategies of conjugating cytotoxic payloads to monoclonal antibodies, insertion of a cysteine residue achieves a tightly controlled, site-specific drug to antibody ratio. 37265400 7 4 theme wildtype 1429:1436 arg1 IgG1 1438:1441 wildtype IgG1 1429:1441 wildtype IgG1 1429:1441 Nearly 20 percent of N-linked glycans contained sialic acid, substantially higher than anticipated for wildtype IgG1. 37265400 8 5 theme constant 1535:1542 arg1 domain 1544:1549 the C239i constant domain 1525:1549 the C239i constant domain 1525:1549 Lastly, previously unreported polypeptide fragmentation sites were identified in the C239i constant domain, and the relationship between fragmentation and glycoform were explored. 37265400 0 6 theme Site-Specific 85:97 arg1 Conjugation 99:109 Site-Specific Conjugation 85:109 Site-Specific Conjugation 85:109 Multi-Attribute Monitoring Method for Process Development of Engineered Antibody for Site-Specific Conjugation. 37265400 4 7 theme interchain 897:906 arg1 bonds 918:922 interchain disulfide bonds 897:922 interchain disulfide bonds 897:922 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 9 8 theme scaffolds 1812:1820 arg1 development 1777:1787 the development 1773:1787 the development of engineered antibody scaffolds 1773:1820 This work illustrates the utility of applying a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method to support the development of engineered antibody scaffolds. 37265400 6 9 theme thiol 1087:1091 arg1 states 1093:1098 Oxidized thiol states 1078:1098 Oxidized thiol states 1078:1098 Oxidized thiol states are formed within the bioreactor, of which a variant containing an additional disulfide bond was produced and remained relatively constant throughout the fed-batch process; reduced thiol variants were introduced upon harvest. 37265400 5 10 theme intermediate 1025:1036 arg1 properties 998:1007 the properties 994:1007 the properties of the antibody intermediate and associated manufacturing processes 994:1075 This method provides new insight into the properties of the antibody intermediate and associated manufacturing processes. 37265400 5 11 theme processes 1067:1075 arg1 properties 998:1007 the properties 994:1007 the properties of the antibody intermediate and associated manufacturing processes 994:1075 This method provides new insight into the properties of the antibody intermediate and associated manufacturing processes. 37265400 5 12 theme associated 1042:1051 arg1 processes 1067:1075 associated manufacturing processes 1042:1075 associated manufacturing processes 1042:1075 This method provides new insight into the properties of the antibody intermediate and associated manufacturing processes. 37265400 9 13 theme antibody 1803:1810 arg1 scaffolds 1812:1820 engineered antibody scaffolds 1792:1820 engineered antibody scaffolds 1792:1820 This work illustrates the utility of applying a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method to support the development of engineered antibody scaffolds. 37265400 4 14 theme distinct 759:766 arg1 attributes 776:785 four distinct quality attributes 754:785 four distinct quality attributes 754:785 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 3 15 theme processes 560:568 arg1 development 545:555 the development 541:555 the development of processes capable of manufacturing novel antibody scaffolds with the desired product quality 541:651 Tailored analytical tools are required to direct the development of processes capable of manufacturing novel antibody scaffolds with the desired product quality. 37265400 4 16 theme quality 768:774 arg1 attributes 776:785 four distinct quality attributes 754:785 four distinct quality attributes 754:785 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 17 theme bonds 918:922 arg1 fragmentation 941:953 polypeptide fragmentation 929:953 polypeptide fragmentation 929:953 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 17 theme bonds 918:922 arg1 reduction 884:892 reduction 884:892 reduction of interchain disulfide bonds 884:922 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 17 theme bonds 918:922 arg1 glycosylation 869:881 N-linked glycosylation 860:881 N-linked glycosylation 860:881 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 17 theme bonds 918:922 arg1 variations 803:812 variations 803:812 variations in the thiol state of the inserted cysteines 803:857 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 18 from variations 803:812 arg1 state 827:831 the thiol state 817:831 the thiol state of the inserted cysteines 817:857 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 3 19 theme capable 570:576 arg1 processes 560:568 processes 560:568 processes capable of manufacturing novel antibody scaffolds with the desired product quality 560:651 Tailored analytical tools are required to direct the development of processes capable of manufacturing novel antibody scaffolds with the desired product quality. 37265400 1 20 theme care 275:278 arg1 approvals 240:248 new approvals 236:248 new approvals 236:248 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 4 21 dep development 676:686 arg1 reduction 884:892 reduction 884:892 reduction of interchain disulfide bonds 884:922 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 21 dep development 676:686 arg1 variations 803:812 variations 803:812 variations in the thiol state of the inserted cysteines 803:857 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 21 dep development 676:686 arg1 glycosylation 869:881 N-linked glycosylation 860:881 N-linked glycosylation 860:881 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 21 dep development 676:686 arg1 fragmentation 941:953 polypeptide fragmentation 929:953 polypeptide fragmentation 929:953 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 22 link N-linked 860:867 arg1 variations 803:812 variations 803:812 variations in the thiol state of the inserted cysteines 803:857 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 22 link N-linked 860:867 arg1 glycosylation 869:881 N-linked glycosylation 860:881 N-linked glycosylation 860:881 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 5 23 theme antibody 1016:1023 arg1 intermediate 1025:1036 the antibody intermediate 1012:1036 the antibody intermediate 1012:1036 This method provides new insight into the properties of the antibody intermediate and associated manufacturing processes. 37265400 2 24 theme cysteine 406:413 arg1 residue 415:421 a cysteine residue 404:421 a cysteine residue 404:421 Among the numerous strategies of conjugating cytotoxic payloads to monoclonal antibodies, insertion of a cysteine residue achieves a tightly controlled, site-specific drug to antibody ratio. 37265400 9 25 theme engineered 1792:1801 arg1 scaffolds 1812:1820 engineered antibody scaffolds 1792:1820 engineered antibody scaffolds 1792:1820 This work illustrates the utility of applying a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method to support the development of engineered antibody scaffolds. 37265400 2 26 dep controlled 442:451 arg1 site-specific 454:466 site-specific 454:466 site-specific 454:466 Among the numerous strategies of conjugating cytotoxic payloads to monoclonal antibodies, insertion of a cysteine residue achieves a tightly controlled, site-specific drug to antibody ratio. 37265400 4 27 theme method 725:730 arg1 development 676:686 the development 672:686 the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation 672:953 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 0 28 theme Monitoring 16:25 arg1 Method 27:32 Multi-Attribute Monitoring Method 0:32 Multi-Attribute Monitoring Method for Process Development of Engineered Antibody for Site-Specific Conjugation. 0:110 Multi-Attribute Monitoring Method for Process Development of Engineered Antibody for Site-Specific Conjugation. 37265400 8 29 theme polypeptide 1474:1484 arg1 sites 1500:1504 previously unreported polypeptide fragmentation sites 1452:1504 previously unreported polypeptide fragmentation sites 1452:1504 Lastly, previously unreported polypeptide fragmentation sites were identified in the C239i constant domain, and the relationship between fragmentation and glycoform were explored. 37265400 5 30 theme manufacturing 1053:1065 arg1 processes 1067:1075 associated manufacturing processes 1042:1075 associated manufacturing processes 1042:1075 This method provides new insight into the properties of the antibody intermediate and associated manufacturing processes. 37265400 3 31 theme novel 595:599 arg1 scaffolds 610:618 novel antibody scaffolds 595:618 novel antibody scaffolds 595:618 Tailored analytical tools are required to direct the development of processes capable of manufacturing novel antibody scaffolds with the desired product quality. 37265400 4 32 theme 12 693:694 arg1 min 696:698 min 696:698 min 696:698 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 0 33 theme Multi-Attribute 0:14 arg1 Method 27:32 Multi-Attribute Monitoring Method 0:32 Multi-Attribute Monitoring Method for Process Development of Engineered Antibody for Site-Specific Conjugation. 0:110 Multi-Attribute Monitoring Method for Process Development of Engineered Antibody for Site-Specific Conjugation. 37265400 9 34 theme multi-attribute 1728:1742 arg1 method 1755:1760 a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method 1670:1760 a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method 1670:1760 This work illustrates the utility of applying a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method to support the development of engineered antibody scaffolds. 37265400 2 35 theme numerous 311:318 arg1 strategies 320:329 the numerous strategies 307:329 the numerous strategies of conjugating cytotoxic payloads to monoclonal antibodies 307:388 Among the numerous strategies of conjugating cytotoxic payloads to monoclonal antibodies, insertion of a cysteine residue achieves a tightly controlled, site-specific drug to antibody ratio. 37265400 9 36 theme high-throughput 1672:1686 arg1 method 1755:1760 a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method 1670:1760 a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method 1670:1760 This work illustrates the utility of applying a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method to support the development of engineered antibody scaffolds. 37265400 7 37 theme higher 1401:1406 arg1 acid 1381:1384 sialic acid 1374:1384 sialic acid 1374:1384 Nearly 20 percent of N-linked glycans contained sialic acid, substantially higher than anticipated for wildtype IgG1. 37265400 1 38 theme cancer 284:289 arg1 patients 291:298 cancer patients 284:298 cancer patients 284:298 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 5 39 theme new 977:979 arg1 insight 981:987 new insight 977:987 new insight into the properties of the antibody intermediate and associated manufacturing processes 977:1075 This method provides new insight into the properties of the antibody intermediate and associated manufacturing processes. 37265400 1 40 theme drug 121:124 arg1 class 140:144 a class 138:144 a class of biotherapeutic proteins 138:171 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 1 40 theme drug 121:124 arg1 conjugates 126:135 Antibody drug conjugates 112:135 Antibody drug conjugates 112:135 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 8 41 theme fragmentation 1486:1498 arg1 sites 1500:1504 previously unreported polypeptide fragmentation sites 1452:1504 previously unreported polypeptide fragmentation sites 1452:1504 Lastly, previously unreported polypeptide fragmentation sites were identified in the C239i constant domain, and the relationship between fragmentation and glycoform were explored. 37265400 1 42 theme recent 209:214 arg1 years 216:220 recent years 209:220 recent years 209:220 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 1 43 theme Antibody 112:119 arg1 class 140:144 a class 138:144 a class of biotherapeutic proteins 138:171 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 1 43 theme Antibody 112:119 arg1 conjugates 126:135 Antibody drug conjugates 112:135 Antibody drug conjugates 112:135 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 6 44 theme fed-batch 1254:1262 arg1 process 1264:1270 the fed-batch process 1250:1270 the fed-batch process 1250:1270 Oxidized thiol states are formed within the bioreactor, of which a variant containing an additional disulfide bond was produced and remained relatively constant throughout the fed-batch process; reduced thiol variants were introduced upon harvest. 37265400 9 45 theme chromatography-mass 1695:1713 arg1 spectrometry 1715:1726 liquid chromatography-mass spectrometry 1688:1726 a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method 1670:1760 This work illustrates the utility of applying a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method to support the development of engineered antibody scaffolds. 37265400 8 46 theme C239i 1529:1533 arg1 domain 1544:1549 the C239i constant domain 1525:1549 the C239i constant domain 1525:1549 Lastly, previously unreported polypeptide fragmentation sites were identified in the C239i constant domain, and the relationship between fragmentation and glycoform were explored. 37265400 4 47 theme capable 732:738 arg1 method 725:730 a 12 min, mass-spectrometry-based method 691:730 a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously 691:800 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 9 48 theme liquid 1688:1693 arg1 spectrometry 1715:1726 liquid chromatography-mass spectrometry 1688:1726 a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method 1670:1760 This work illustrates the utility of applying a high-throughput liquid chromatography-mass spectrometry multi-attribute monitoring method to support the development of engineered antibody scaffolds. 37265400 7 49 contain contained 1364:1372 arg1 percent 1336:1342 Nearly 20 percent 1326:1342 Nearly 20 percent of N-linked glycans 1326:1362 Nearly 20 percent of N-linked glycans contained sialic acid, substantially higher than anticipated for wildtype IgG1. 37265400 7 49 contain contained 1364:1372 arg2 acid 1381:1384 sialic acid 1374:1384 sialic acid 1374:1384 Nearly 20 percent of N-linked glycans contained sialic acid, substantially higher than anticipated for wildtype IgG1. 37265400 4 50 theme cysteines 849:857 arg1 state 827:831 the thiol state 817:831 the thiol state of the inserted cysteines 817:857 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 3 51 theme antibody 601:608 arg1 scaffolds 610:618 novel antibody scaffolds 595:618 novel antibody scaffolds 595:618 Tailored analytical tools are required to direct the development of processes capable of manufacturing novel antibody scaffolds with the desired product quality. 37265400 0 52 theme Process 38:44 arg1 Development 46:56 Process Development 38:56 Process Development of Engineered Antibody 38:79 Multi-Attribute Monitoring Method for Process Development of Engineered Antibody for Site-Specific Conjugation. 37265400 3 53 theme desired 629:635 arg1 quality 645:651 the desired product quality 625:651 the desired product quality 625:651 Tailored analytical tools are required to direct the development of processes capable of manufacturing novel antibody scaffolds with the desired product quality. 37265400 2 54 theme residue 415:421 arg1 insertion 391:399 insertion 391:399 insertion of a cysteine residue 391:421 Among the numerous strategies of conjugating cytotoxic payloads to monoclonal antibodies, insertion of a cysteine residue achieves a tightly controlled, site-specific drug to antibody ratio. 37265400 2 55 theme antibody 476:483 arg1 ratio 485:489 antibody ratio 476:489 antibody ratio 476:489 Among the numerous strategies of conjugating cytotoxic payloads to monoclonal antibodies, insertion of a cysteine residue achieves a tightly controlled, site-specific drug to antibody ratio. 37265400 4 56 theme polypeptide 929:939 arg1 fragmentation 941:953 polypeptide fragmentation 929:953 polypeptide fragmentation 929:953 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 56 theme polypeptide 929:939 arg1 variations 803:812 variations 803:812 variations in the thiol state of the inserted cysteines 803:857 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 0 57 theme Antibody 72:79 arg1 Development 46:56 Process Development 38:56 Process Development of Engineered Antibody 38:79 Multi-Attribute Monitoring Method for Process Development of Engineered Antibody for Site-Specific Conjugation. 37265400 4 58 theme N-linked 860:867 arg1 variations 803:812 variations 803:812 variations in the thiol state of the inserted cysteines 803:857 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 4 58 theme N-linked 860:867 arg1 glycosylation 869:881 N-linked glycosylation 860:881 N-linked glycosylation 860:881 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 6 59 theme disulfide 1178:1186 arg1 bond 1188:1191 an additional disulfide bond 1164:1191 an additional disulfide bond 1164:1191 Oxidized thiol states are formed within the bioreactor, of which a variant containing an additional disulfide bond was produced and remained relatively constant throughout the fed-batch process; reduced thiol variants were introduced upon harvest. 37265400 7 60 theme N-linked 1347:1354 arg1 glycans 1356:1362 N-linked glycans 1347:1362 N-linked glycans 1347:1362 Nearly 20 percent of N-linked glycans contained sialic acid, substantially higher than anticipated for wildtype IgG1. 37265400 2 61 theme cytotoxic 346:354 arg1 payloads 356:363 cytotoxic payloads 346:363 cytotoxic payloads 346:363 Among the numerous strategies of conjugating cytotoxic payloads to monoclonal antibodies, insertion of a cysteine residue achieves a tightly controlled, site-specific drug to antibody ratio. 37265400 4 62 theme inserted 840:847 arg1 cysteines 849:857 the inserted cysteines 836:857 the inserted cysteines 836:857 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 7 63 link N-linked 1347:1354 arg1 glycans 1356:1362 N-linked glycans 1347:1362 N-linked glycans 1347:1362 Nearly 20 percent of N-linked glycans contained sialic acid, substantially higher than anticipated for wildtype IgG1. 37265400 6 64 theme thiol 1281:1285 arg1 variants 1287:1294 reduced thiol variants 1273:1294 reduced thiol variants 1273:1294 Oxidized thiol states are formed within the bioreactor, of which a variant containing an additional disulfide bond was produced and remained relatively constant throughout the fed-batch process; reduced thiol variants were introduced upon harvest. 37265400 4 65 theme min 696:698 arg1 method 725:730 a 12 min, mass-spectrometry-based method 691:730 a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously 691:800 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 3 66 theme Tailored 492:499 arg1 tools 512:516 Tailored analytical tools 492:516 Tailored analytical tools 492:516 Tailored analytical tools are required to direct the development of processes capable of manufacturing novel antibody scaffolds with the desired product quality. 37265400 6 67 theme additional 1167:1176 arg1 bond 1188:1191 an additional disulfide bond 1164:1191 an additional disulfide bond 1164:1191 Oxidized thiol states are formed within the bioreactor, of which a variant containing an additional disulfide bond was produced and remained relatively constant throughout the fed-batch process; reduced thiol variants were introduced upon harvest. 37265400 4 68 dep min 696:698 arg1 mass-spectrometry-based 701:723 mass-spectrometry-based 701:723 mass-spectrometry-based 701:723 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 6 69 contain containing 1153:1162 arg2 bond 1188:1191 an additional disulfide bond 1164:1191 an additional disulfide bond 1164:1191 Oxidized thiol states are formed within the bioreactor, of which a variant containing an additional disulfide bond was produced and remained relatively constant throughout the fed-batch process; reduced thiol variants were introduced upon harvest. 37265400 6 69 contain containing 1153:1162 arg1 variant 1145:1151 a variant 1143:1151 a variant containing an additional disulfide bond 1143:1191 Oxidized thiol states are formed within the bioreactor, of which a variant containing an additional disulfide bond was produced and remained relatively constant throughout the fed-batch process; reduced thiol variants were introduced upon harvest. 37265400 4 70 theme thiol 821:825 arg1 state 827:831 the thiol state 817:831 the thiol state of the inserted cysteines 817:857 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 3 71 theme analytical 501:510 arg1 tools 512:516 Tailored analytical tools 492:516 Tailored analytical tools 492:516 Tailored analytical tools are required to direct the development of processes capable of manufacturing novel antibody scaffolds with the desired product quality. 37265400 6 72 theme reduced 1273:1279 arg1 variants 1287:1294 reduced thiol variants 1273:1294 reduced thiol variants 1273:1294 Oxidized thiol states are formed within the bioreactor, of which a variant containing an additional disulfide bond was produced and remained relatively constant throughout the fed-batch process; reduced thiol variants were introduced upon harvest. 37265400 1 73 theme new 236:238 arg1 approvals 240:248 new approvals 236:248 new approvals 236:248 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 7 74 theme sialic 1374:1379 arg1 acid 1381:1384 sialic acid 1374:1384 sialic acid 1374:1384 Nearly 20 percent of N-linked glycans contained sialic acid, substantially higher than anticipated for wildtype IgG1. 37265400 3 75 theme product 637:643 arg1 quality 645:651 the desired product quality 625:651 the desired product quality 625:651 Tailored analytical tools are required to direct the development of processes capable of manufacturing novel antibody scaffolds with the desired product quality. 37265400 4 76 gly glycosylation 869:881 arg1 bonds 918:922 interchain disulfide bonds 897:922 interchain disulfide bonds 897:922 Here, we describe the development of a 12 min, mass-spectrometry-based method capable of monitoring four distinct quality attributes simultaneously: variations in the thiol state of the inserted cysteines, N-linked glycosylation, reduction of interchain disulfide bonds, and polypeptide fragmentation. 37265400 1 77 theme biotherapeutic 149:162 arg1 proteins 164:171 biotherapeutic proteins 149:171 biotherapeutic proteins 149:171 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 8 78 theme unreported 1463:1472 arg1 sites 1500:1504 previously unreported polypeptide fragmentation sites 1452:1504 previously unreported polypeptide fragmentation sites 1452:1504 Lastly, previously unreported polypeptide fragmentation sites were identified in the C239i constant domain, and the relationship between fragmentation and glycoform were explored. 37265400 6 79 theme Oxidized 1078:1085 arg1 states 1093:1098 Oxidized thiol states 1078:1098 Oxidized thiol states 1078:1098 Oxidized thiol states are formed within the bioreactor, of which a variant containing an additional disulfide bond was produced and remained relatively constant throughout the fed-batch process; reduced thiol variants were introduced upon harvest. 37265400 0 80 theme Engineered 61:70 arg1 Antibody 72:79 Engineered Antibody 61:79 Engineered Antibody 61:79 Multi-Attribute Monitoring Method for Process Development of Engineered Antibody for Site-Specific Conjugation. 37265400 2 81 theme controlled 442:451 arg1 drug 468:471 a tightly controlled, site-specific drug 432:471 a tightly controlled, site-specific drug to antibody ratio 432:489 Among the numerous strategies of conjugating cytotoxic payloads to monoclonal antibodies, insertion of a cysteine residue achieves a tightly controlled, site-specific drug to antibody ratio. 37265400 1 82 theme proteins 164:171 arg1 class 140:144 a class 138:144 a class of biotherapeutic proteins 138:171 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 1 82 theme proteins 164:171 arg1 conjugates 126:135 Antibody drug conjugates 112:135 Antibody drug conjugates 112:135 Antibody drug conjugates, a class of biotherapeutic proteins, have been extensively developed in recent years, resulting in new approvals and improved standard of care for cancer patients. 37265400 7 83 theme glycans 1356:1362 arg1 percent 1336:1342 Nearly 20 percent 1326:1342 Nearly 20 percent of N-linked glycans 1326:1362 Nearly 20 percent of N-linked glycans contained sialic acid, substantially higher than anticipated for wildtype IgG1. 35301431 4 0 theme GLT8D1 651:656 arg1 Depletion 638:646 Depletion 638:646 Depletion of GLT8D1 638:656 Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. 35301431 0 1 link N-linked 101:108 arg1 glycosylation 110:122 N-linked glycosylation 101:122 N-linked glycosylation 101:122 Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. 35301431 8 2 theme mechanistic 1324:1334 arg1 insights 1336:1343 mechanistic insights 1324:1343 mechanistic insights into how hypoxia promotes GLT8D1/CD133/Wnt/β-catenin signaling during glioma progression 1324:1432 Collectively, these findings offer mechanistic insights into how hypoxia promotes GLT8D1/CD133/Wnt/β-catenin signaling during glioma progression, and identify GLT8D1 as a potential therapeutic target in the future. 35301431 6 3 theme N-linked 969:976 arg1 glycosylation 978:990 N-linked glycosylation 969:990 N-linked glycosylation 969:990 We reveal that GLT8D1 impedes CD133 degradation through the endosomal-lysosomal pathway by N-linked glycosylation and protein-protein interaction. 35301431 7 4 theme signaling 1194:1202 arg1 tumorigenesis 1214:1226 Wnt/β-catenin signaling dependent tumorigenesis 1180:1226 Wnt/β-catenin signaling dependent tumorigenesis 1180:1226 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 3 5 theme glioma 600:605 arg1 grade 591:595 a higher grade 582:595 a higher grade of glioma 582:605 Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. 35301431 3 5 theme glioma 600:605 arg1 outcome 629:635 a worse clinical outcome 612:635 a worse clinical outcome 612:635 Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. 35301431 2 6 theme radiation 288:296 arg1 addition 254:261 the addition 250:261 the addition of temozolomide (TMZ) or radiation as initial therapy 250:315 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 4 7 from growth 735:740 arg1 models 758:763 glioma mouse models 745:763 glioma mouse models 745:763 Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. 35301431 6 8 theme endosomal-lysosomal 938:956 arg1 pathway 958:964 the endosomal-lysosomal pathway 934:964 the endosomal-lysosomal pathway 934:964 We reveal that GLT8D1 impedes CD133 degradation through the endosomal-lysosomal pathway by N-linked glycosylation and protein-protein interaction. 35301431 2 9 from improvement 203:213 arg1 survival 218:225 survival 218:225 survival 218:225 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 6 10 link N-linked 969:976 arg1 glycosylation 978:990 N-linked glycosylation 969:990 N-linked glycosylation 969:990 We reveal that GLT8D1 impedes CD133 degradation through the endosomal-lysosomal pathway by N-linked glycosylation and protein-protein interaction. 35301431 4 11 theme cell 695:698 arg1 self-renewal 667:678 self-renewal 667:678 self-renewal 667:678 Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. 35301431 3 12 theme domain 481:486 arg1 GLT8D1 502:507 glycosyltransferase 8 domain containing 1 (GLT8D1) 459:508 glycosyltransferase 8 domain containing 1 (GLT8D1) 459:508 Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. 35301431 4 13 theme glioma 683:688 arg1 GSC 701:703 GSC 701:703 GSC 701:703 Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. 35301431 4 13 theme glioma 683:688 arg1 cell 695:698 glioma stem cell 683:698 glioma stem cell (GSC) 683:704 Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. 35301431 5 14 theme cell 792:795 arg1 arrest 803:808 cell cycle arrest 792:808 cell cycle arrest at G2/M phase 792:822 GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. 35301431 3 15 theme glycosyltransferase 459:477 arg1 GLT8D1 502:507 glycosyltransferase 8 domain containing 1 (GLT8D1) 459:508 glycosyltransferase 8 domain containing 1 (GLT8D1) 459:508 Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. 35301431 4 16 theme tumor 729:733 arg1 growth 735:740 tumor growth 729:740 tumor growth in glioma mouse models 729:763 Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. 35301431 2 17 theme signaling 389:397 arg1 pathways 399:406 various signaling pathways 381:406 various signaling pathways 381:406 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 7 18 theme Wnt/β-catenin 1180:1192 arg1 tumorigenesis 1214:1226 Wnt/β-catenin signaling dependent tumorigenesis 1180:1226 Wnt/β-catenin signaling dependent tumorigenesis 1180:1226 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 8 19 dep potential 1460:1468 arg1 therapeutic 1470:1480 therapeutic 1470:1480 therapeutic 1470:1480 Collectively, these findings offer mechanistic insights into how hypoxia promotes GLT8D1/CD133/Wnt/β-catenin signaling during glioma progression, and identify GLT8D1 as a potential therapeutic target in the future. 35301431 8 20 theme GLT8D1/CD133/Wnt/β-catenin 1371:1396 arg1 signaling 1398:1406 GLT8D1/CD133/Wnt/β-catenin signaling 1371:1406 GLT8D1/CD133/Wnt/β-catenin signaling 1371:1406 Collectively, these findings offer mechanistic insights into how hypoxia promotes GLT8D1/CD133/Wnt/β-catenin signaling during glioma progression, and identify GLT8D1 as a potential therapeutic target in the future. 35301431 2 21 theme various 381:387 arg1 pathways 399:406 various signaling pathways 381:406 various signaling pathways 381:406 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 8 22 theme glioma 1415:1420 arg1 progression 1422:1432 glioma progression 1415:1432 glioma progression 1415:1432 Collectively, these findings offer mechanistic insights into how hypoxia promotes GLT8D1/CD133/Wnt/β-catenin signaling during glioma progression, and identify GLT8D1 as a potential therapeutic target in the future. 35301431 0 23 theme Hypoxia-induced 0:14 arg1 GLT8D1 16:21 Hypoxia-induced GLT8D1 0:21 Hypoxia-induced GLT8D1 0:21 Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. 35301431 7 24 theme GLT8D1 1133:1138 arg1 expression 1140:1149 GLT8D1 expression 1133:1149 GLT8D1 expression 1133:1149 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 4 25 theme stem 690:693 arg1 GSC 701:703 GSC 701:703 GSC 701:703 Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. 35301431 4 25 theme stem 690:693 arg1 cell 695:698 glioma stem cell 683:698 glioma stem cell (GSC) 683:704 Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. 35301431 8 26 from target 1482:1487 arg1 future 1496:1501 future 1496:1501 future 1496:1501 Collectively, these findings offer mechanistic insights into how hypoxia promotes GLT8D1/CD133/Wnt/β-catenin signaling during glioma progression, and identify GLT8D1 as a potential therapeutic target in the future. 35301431 0 27 theme glioma 32:37 arg1 maintenance 49:59 glioma stem cell maintenance 32:59 glioma stem cell maintenance 32:59 Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. 35301431 4 28 theme mouse 752:756 arg1 models 758:763 glioma mouse models 745:763 glioma mouse models 745:763 Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. 35301431 7 29 theme complex 1060:1066 arg1 formation 1068:1076 the GLT8D1/CD133 complex formation 1043:1076 the GLT8D1/CD133 complex formation 1043:1076 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 7 30 theme patient-derived 1249:1263 arg1 xenografts 1265:1274 patient-derived xenografts 1249:1274 patient-derived xenografts mouse model 1249:1286 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 2 31 theme initial 301:307 arg1 therapy 309:315 initial therapy 301:315 initial therapy 301:315 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 2 32 theme driver 420:425 arg1 mutations 427:435 putative driver mutations 411:435 putative driver mutations 411:435 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 6 33 theme CD133 908:912 arg1 degradation 914:924 CD133 degradation 908:924 CD133 degradation 908:924 We reveal that GLT8D1 impedes CD133 degradation through the endosomal-lysosomal pathway by N-linked glycosylation and protein-protein interaction. 35301431 7 34 dep both 1228:1231 arg1 vitro 1236:1240 vitro 1236:1240 vitro 1236:1240 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 2 35 theme significant 191:201 arg1 improvement 203:213 no significant improvement 188:213 no significant improvement in survival 188:225 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 3 36 theme hypoxic 537:543 arg1 niche 545:549 a hypoxic niche 535:549 a hypoxic niche 535:549 Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. 35301431 2 37 theme putative 411:418 arg1 mutations 427:435 putative driver mutations 411:435 putative driver mutations 411:435 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 0 38 theme cell 44:47 arg1 maintenance 49:59 glioma stem cell maintenance 32:59 glioma stem cell maintenance 32:59 Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. 35301431 5 39 theme TMZ 863:865 arg1 treatment 867:875 TMZ treatment 863:875 TMZ treatment 863:875 GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. 35301431 7 40 link patient-derived 1249:1263 arg1 xenografts 1265:1274 patient-derived xenografts 1249:1274 patient-derived xenografts mouse model 1249:1286 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 3 41 theme worse 614:618 arg1 outcome 629:635 a worse clinical outcome 612:635 a worse clinical outcome 612:635 Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. 35301431 5 42 theme cycle 797:801 arg1 arrest 803:808 cell cycle arrest 792:808 cell cycle arrest at G2/M phase 792:822 GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. 35301431 0 43 theme stem 39:42 arg1 maintenance 49:59 glioma stem cell maintenance 32:59 glioma stem cell maintenance 32:59 Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. 35301431 7 44 theme GLT8D1/CD133 1047:1058 arg1 formation 1068:1076 the GLT8D1/CD133 complex formation 1043:1076 the GLT8D1/CD133 complex formation 1043:1076 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 5 45 theme GLT8D1 766:771 arg1 knockdown 773:781 GLT8D1 knockdown 766:781 GLT8D1 knockdown 766:781 GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. 35301431 5 46 theme cellular 828:835 arg1 apoptosis 837:845 cellular apoptosis 828:845 cellular apoptosis with or without TMZ treatment 828:875 GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. 35301431 7 47 dep suppresses 1169:1178 arg1 inhibiting 1122:1131 inhibiting 1122:1131 inhibiting GLT8D1 expression by lercanidipine 1122:1166 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 7 47 dep suppresses 1169:1178 arg1 model 1282:1286 patient-derived xenografts mouse model 1249:1286 patient-derived xenografts mouse model 1249:1286 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 7 47 dep suppresses 1169:1178 arg1 blocking 1034:1041 blocking 1034:1041 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133) 1025:1116 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 7 47 dep suppresses 1169:1178 arg1 both 1228:1231 both 1228:1231 both 1228:1231 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 7 48 dep CD133N1~108 1081:1091 arg1 referred 1094:1101 referred 1094:1101 referred to as FECD133 1094:1115 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 3 49 theme containing 488:497 arg1 GLT8D1 502:507 glycosyltransferase 8 domain containing 1 (GLT8D1) 459:508 glycosyltransferase 8 domain containing 1 (GLT8D1) 459:508 Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. 35301431 7 50 theme dependent 1204:1212 arg1 tumorigenesis 1214:1226 Wnt/β-catenin signaling dependent tumorigenesis 1180:1226 Wnt/β-catenin signaling dependent tumorigenesis 1180:1226 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 2 51 theme clinical 332:339 arg1 efforts 341:347 many clinical efforts 327:347 many clinical efforts 327:347 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 7 52 theme xenografts 1265:1274 arg1 model 1282:1286 patient-derived xenografts mouse model 1249:1286 patient-derived xenografts mouse model 1249:1286 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 8 53 theme potential 1460:1468 arg1 GLT8D1 1448:1453 GLT8D1 1448:1453 GLT8D1 1448:1453 Collectively, these findings offer mechanistic insights into how hypoxia promotes GLT8D1/CD133/Wnt/β-catenin signaling during glioma progression, and identify GLT8D1 as a potential therapeutic target in the future. 35301431 8 53 theme potential 1460:1468 arg1 target 1482:1487 a potential therapeutic target 1458:1487 a potential therapeutic target in the future 1458:1501 Collectively, these findings offer mechanistic insights into how hypoxia promotes GLT8D1/CD133/Wnt/β-catenin signaling during glioma progression, and identify GLT8D1 as a potential therapeutic target in the future. 35301431 1 54 theme most 141:144 arg1 tumors 171:176 the most aggressive primary brain tumors 137:176 the most aggressive primary brain tumors 137:176 Gliomas are the most aggressive primary brain tumors. 35301431 1 54 theme most 141:144 arg1 Gliomas 125:131 Gliomas 125:131 Gliomas 125:131 Gliomas are the most aggressive primary brain tumors. 35301431 6 55 theme protein-protein 996:1010 arg1 interaction 1012:1022 protein-protein interaction 996:1022 protein-protein interaction 996:1022 We reveal that GLT8D1 impedes CD133 degradation through the endosomal-lysosomal pathway by N-linked glycosylation and protein-protein interaction. 35301431 3 56 theme clinical 620:627 arg1 outcome 629:635 a worse clinical outcome 612:635 a worse clinical outcome 612:635 Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. 35301431 2 57 theme temozolomide 266:277 arg1 addition 254:261 the addition 250:261 the addition of temozolomide (TMZ) or radiation as initial therapy 250:315 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 5 58 from phase 818:822 arg1 arrest 803:808 cell cycle arrest 792:808 cell cycle arrest at G2/M phase 792:822 GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. 35301431 5 58 from phase 818:822 arg1 apoptosis 837:845 cellular apoptosis 828:845 cellular apoptosis with or without TMZ treatment 828:875 GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. 35301431 1 59 theme aggressive 146:155 arg1 tumors 171:176 the most aggressive primary brain tumors 137:176 the most aggressive primary brain tumors 137:176 Gliomas are the most aggressive primary brain tumors. 35301431 1 59 theme aggressive 146:155 arg1 Gliomas 125:131 Gliomas 125:131 Gliomas 125:131 Gliomas are the most aggressive primary brain tumors. 35301431 2 60 theme many 327:330 arg1 efforts 341:347 many clinical efforts 327:347 many clinical efforts 327:347 However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. 35301431 0 61 theme CD133 75:79 arg1 degradation 81:91 CD133 degradation 75:91 CD133 degradation 75:91 Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. 35301431 3 62 theme higher 584:589 arg1 grade 591:595 a higher grade 582:595 a higher grade of glioma 582:605 Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. 35301431 1 63 theme primary 157:163 arg1 tumors 171:176 the most aggressive primary brain tumors 137:176 the most aggressive primary brain tumors 137:176 Gliomas are the most aggressive primary brain tumors. 35301431 1 63 theme primary 157:163 arg1 Gliomas 125:131 Gliomas 125:131 Gliomas 125:131 Gliomas are the most aggressive primary brain tumors. 35301431 5 64 theme G2/M 813:816 arg1 phase 818:822 G2/M phase 813:822 G2/M phase 813:822 GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. 35301431 4 65 theme glioma 745:750 arg1 models 758:763 glioma mouse models 745:763 glioma mouse models 745:763 Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. 35301431 7 66 theme mouse 1276:1280 arg1 model 1282:1286 patient-derived xenografts mouse model 1249:1286 patient-derived xenografts mouse model 1249:1286 Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/β-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. 35301431 1 67 theme brain 165:169 arg1 tumors 171:176 the most aggressive primary brain tumors 137:176 the most aggressive primary brain tumors 137:176 Gliomas are the most aggressive primary brain tumors. 35301431 1 67 theme brain 165:169 arg1 Gliomas 125:131 Gliomas 125:131 Gliomas 125:131 Gliomas are the most aggressive primary brain tumors. 35301431 0 68 theme N-linked 101:108 arg1 glycosylation 110:122 N-linked glycosylation 101:122 N-linked glycosylation 101:122 Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. 36535622 12 0 theme freezability 1800:1811 arg1 factor 1864:1869 a limiting factor 1853:1869 a limiting factor of sperm cryopreservation 1853:1895 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 12 0 theme freezability 1800:1811 arg1 difference 1813:1822 The freezability difference 1796:1822 The freezability difference between donkey ejaculates 1796:1848 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 17 1 theme good 2570:2573 arg1 freezability 2581:2592 good sperm freezability 2570:2592 good sperm freezability 2570:2592 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 4 2 theme 2682 545:548 arg1 proteins 550:557 2682 proteins 545:557 2682 proteins 545:557 A total of 2682 proteins were identified, among which 58 were significantly up-regulated in GFEs and 16 were down-regulated compared with PFEs. 36535622 10 3 dep sperm 1620:1624 arg1 motility 1626:1633 motility 1626:1633 motility 1626:1633 However, semen cryopreservation is a damaging process, which can cause oxidative stress, reduce sperm motility and motility. 36535622 3 4 theme TMT 480:482 arg1 labeling 493:500 a Tandem Mass Tag (TMT) peptide labeling 461:500 a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach 461:531 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 17 5 theme candidate 2418:2426 arg1 proteins 2428:2435 The identified candidate proteins 2403:2435 The identified candidate proteins 2403:2435 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 3 6 theme LC-MS/MS 515:522 arg1 approach 524:531 LC-MS/MS approach 515:531 LC-MS/MS approach 515:531 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 1 7 theme donkey 131:136 arg1 ejaculates 138:147 donkey ejaculates 131:147 donkey ejaculates 131:147 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 2 8 theme seminal 276:282 arg1 proteome 291:298 the seminal plasma proteome 272:298 the seminal plasma proteome 272:298 Our recent study shows that the freezability of donkey semen is related to the seminal plasma proteome. 36535622 5 9 theme RNA 833:835 arg1 process 850:856 RNA biosynthetic process 833:856 RNA biosynthetic process 833:856 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 17 10 theme sperm 2504:2508 arg1 cryotolerance 2510:2522 donkey sperm cryotolerance 2497:2522 donkey sperm cryotolerance 2497:2522 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 8 11 theme identified 1244:1253 arg1 proteins 1265:1272 The identified candidate proteins 1240:1272 The identified candidate proteins 1240:1272 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 5 12 theme process 850:856 arg1 regulation 868:877 positive regulation 859:877 positive regulation of innate immune response 859:903 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 5 12 theme process 850:856 arg1 regulation 919:928 negative regulation 910:928 negative regulation of programmed cell death 910:953 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 5 12 theme process 850:856 arg1 regulation 819:828 regulation 819:828 regulation of RNA biosynthetic process 819:856 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 1 13 theme freezability 99:110 arg1 factor 163:168 a limiting factor 152:168 a limiting factor of sperm cryopreservation 152:194 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 1 13 theme freezability 99:110 arg1 difference 112:121 The freezability difference 95:121 The freezability difference between donkey ejaculates 95:147 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 9 14 theme reproductive 1499:1510 arg1 technology 1512:1521 assisted reproductive technology 1490:1521 assisted reproductive technology 1490:1521 SIGNIFICANCE: Cryopreserved semen has been widely used in assisted reproductive technology. 36535622 5 15 theme analysis 692:699 arg1 results 701:707 Bioinformatic analysis results 678:707 Bioinformatic analysis results 678:707 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 2 16 theme donkey 245:250 arg1 semen 252:256 donkey semen 245:256 donkey semen 245:256 Our recent study shows that the freezability of donkey semen is related to the seminal plasma proteome. 36535622 7 17 from ejaculates 1198:1207 arg1 proteome 1168:1175 the proteome 1164:1175 the proteome of sperm from donkey ejaculates with different freezabilities 1164:1237 Our study was the first to analyze the proteome of sperm from donkey ejaculates with different freezabilities. 36535622 5 18 theme immune 889:894 arg1 response 896:903 innate immune response 882:903 innate immune response 882:903 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 9 19 dep SIGNIFICANCE 1432:1443 arg1 semen 1460:1464 Cryopreserved semen 1446:1464 SIGNIFICANCE: Cryopreserved semen 1432:1464 SIGNIFICANCE: Cryopreserved semen has been widely used in assisted reproductive technology. 36535622 16 20 theme novel 2325:2329 arg1 biomarkers 2331:2340 Additional novel biomarkers 2314:2340 Additional novel biomarkers of semen freezability in donkey spermatozoa 2314:2384 Additional novel biomarkers of semen freezability in donkey spermatozoa are also needed. 36535622 5 21 theme innate 882:887 arg1 response 896:903 innate immune response 882:903 innate immune response 882:903 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 6 22 theme up-regulated 1000:1011 arg1 proteins 1013:1020 the up-regulated proteins 996:1020 the up-regulated proteins in GF group 996:1032 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 13 23 theme sperm 1952:1956 arg1 quality 1958:1964 sperm quality 1952:1964 sperm quality 1952:1964 The mechanisms that affect the freezing difference in sperm quality remain to be investigated, and freezability differences was found to be related to protein composition of spermatozoa. 36535622 7 24 theme different 1214:1222 arg1 freezabilities 1224:1237 different freezabilities 1214:1237 different freezabilities 1214:1237 Our study was the first to analyze the proteome of sperm from donkey ejaculates with different freezabilities. 36535622 5 25 theme positive 859:866 arg1 regulation 868:877 positive regulation 859:877 positive regulation of innate immune response 859:903 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 16 26 theme freezability 2351:2362 arg1 biomarkers 2331:2340 Additional novel biomarkers 2314:2340 Additional novel biomarkers of semen freezability in donkey spermatozoa 2314:2384 Additional novel biomarkers of semen freezability in donkey spermatozoa are also needed. 36535622 8 27 with screening 1383:1391 arg1 freezability 1418:1429 good sperm freezability 1407:1429 good sperm freezability 1407:1429 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 5 28 theme abundance 749:757 arg1 DAPs 769:772 DAPs 769:772 DAPs 769:772 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 5 28 theme abundance 749:757 arg1 proteins 759:766 different abundance proteins 739:766 different abundance proteins (DAPs) 739:773 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 1 29 theme sperm 173:177 arg1 cryopreservation 179:194 sperm cryopreservation 173:194 sperm cryopreservation 173:194 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 6 30 theme enrichment 969:978 arg1 analysis 980:987 KEGG pathway enrichment analysis 956:987 KEGG pathway enrichment analysis 956:987 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 3 31 theme abundance 351:359 arg1 proteins 367:374 the different abundance sperm proteins 337:374 the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) 337:453 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 6 32 from proteins 1013:1020 arg1 group 1028:1032 GF group 1025:1032 GF group 1025:1032 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 8 33 theme sperm 1341:1345 arg1 cryotolerance 1347:1359 donkey sperm cryotolerance 1334:1359 donkey sperm cryotolerance 1334:1359 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 16 34 theme donkey 2367:2372 arg1 spermatozoa 2374:2384 donkey spermatozoa 2367:2384 donkey spermatozoa 2367:2384 Additional novel biomarkers of semen freezability in donkey spermatozoa are also needed. 36535622 3 35 from proteins 367:374 arg1 PFEs 449:452 PFEs 449:452 PFEs 449:452 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 3 35 from proteins 367:374 arg1 ejaculates 437:446 poor freezability ejaculates 419:446 poor freezability ejaculates (PFEs) 419:453 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 3 35 from proteins 367:374 arg1 GFEs 409:412 GFEs 409:412 GFEs 409:412 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 3 35 from proteins 367:374 arg1 ejaculates 397:406 good freezability ejaculates 379:406 good freezability ejaculates (GFEs) 379:413 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 5 36 theme cell 944:947 arg1 death 949:953 programmed cell death 933:953 programmed cell death 933:953 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 6 37 theme KEGG 956:959 arg1 analysis 980:987 KEGG pathway enrichment analysis 956:987 KEGG pathway enrichment analysis 956:987 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 6 38 dep showed 989:994 arg1 involved 1046:1053 involved 1046:1053 showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum 989:1126 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 3 39 theme freezability 424:435 arg1 PFEs 449:452 PFEs 449:452 PFEs 449:452 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 3 39 theme freezability 424:435 arg1 ejaculates 437:446 poor freezability ejaculates 419:446 poor freezability ejaculates (PFEs) 419:453 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 13 40 theme spermatozoa 2072:2082 arg1 composition 2057:2067 protein composition 2049:2067 protein composition of spermatozoa 2049:2082 The mechanisms that affect the freezing difference in sperm quality remain to be investigated, and freezability differences was found to be related to protein composition of spermatozoa. 36535622 0 41 theme Dezhou 44:49 arg1 analysis 32:39 TMT-based comparative proteomic analysis 0:39 TMT-based comparative proteomic analysis of Dezhou 0:49 TMT-based comparative proteomic analysis of Dezhou donkey spermatozoa related to freezability. 36535622 3 42 theme good 379:382 arg1 GFEs 409:412 GFEs 409:412 GFEs 409:412 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 3 42 theme good 379:382 arg1 ejaculates 397:406 good freezability ejaculates 379:406 good freezability ejaculates (GFEs) 379:413 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 0 43 theme TMT-based 0:8 arg1 analysis 32:39 TMT-based comparative proteomic analysis 0:39 TMT-based comparative proteomic analysis of Dezhou 0:49 TMT-based comparative proteomic analysis of Dezhou donkey spermatozoa related to freezability. 36535622 5 44 theme negative 910:917 arg1 regulation 919:928 negative regulation 910:928 negative regulation of programmed cell death 910:953 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 0 45 theme proteomic 22:30 arg1 analysis 32:39 TMT-based comparative proteomic analysis 0:39 TMT-based comparative proteomic analysis of Dezhou 0:49 TMT-based comparative proteomic analysis of Dezhou donkey spermatozoa related to freezability. 36535622 12 46 theme sperm 1874:1878 arg1 cryopreservation 1880:1895 sperm cryopreservation 1874:1895 sperm cryopreservation 1874:1895 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 13 47 from difference 1938:1947 arg1 quality 1958:1964 sperm quality 1952:1964 sperm quality 1952:1964 The mechanisms that affect the freezing difference in sperm quality remain to be investigated, and freezability differences was found to be related to protein composition of spermatozoa. 36535622 14 48 theme protein 2090:2096 arg1 markers 2098:2104 Some protein markers 2085:2104 Some protein markers that can indicate good freezability or poor freezability semen 2085:2167 Some protein markers that can indicate good freezability or poor freezability semen have been identified in mammals. 36535622 8 49 theme jacks 1396:1400 arg1 screening 1383:1391 the screening 1379:1391 the screening of jacks with good sperm freezability 1379:1429 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 15 50 theme spermatozoa 2275:2285 arg1 proteome 2287:2294 donkey spermatozoa proteome 2268:2294 donkey spermatozoa proteome 2268:2294 Until now, there is no information about the relationship between donkey spermatozoa proteome and freezability. 36535622 12 51 theme donkey 1832:1837 arg1 ejaculates 1839:1848 donkey ejaculates 1832:1848 donkey ejaculates 1832:1848 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 8 52 theme good 1407:1410 arg1 freezability 1418:1429 good sperm freezability 1407:1429 good sperm freezability 1407:1429 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 3 53 theme Mass 470:473 arg1 labeling 493:500 a Tandem Mass Tag (TMT) peptide labeling 461:500 a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach 461:531 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 13 54 theme protein 2049:2055 arg1 composition 2057:2067 protein composition 2049:2067 protein composition of spermatozoa 2049:2082 The mechanisms that affect the freezing difference in sperm quality remain to be investigated, and freezability differences was found to be related to protein composition of spermatozoa. 36535622 6 55 from biosynthesis 1067:1078 arg1 reticulum 1118:1126 endoplasmic reticulum 1106:1126 endoplasmic reticulum 1106:1126 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 9 56 theme Cryopreserved 1446:1458 arg1 semen 1460:1464 Cryopreserved semen 1446:1464 SIGNIFICANCE: Cryopreserved semen 1432:1464 SIGNIFICANCE: Cryopreserved semen has been widely used in assisted reproductive technology. 36535622 6 57 theme protein 1084:1090 arg1 processing 1092:1101 protein processing 1084:1101 protein processing 1084:1101 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 7 58 theme donkey 1191:1196 arg1 ejaculates 1198:1207 donkey ejaculates 1191:1207 donkey ejaculates with different freezabilities 1191:1237 Our study was the first to analyze the proteome of sperm from donkey ejaculates with different freezabilities. 36535622 17 59 with screening 2546:2554 arg1 freezability 2581:2592 good sperm freezability 2570:2592 good sperm freezability 2570:2592 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 17 60 theme sperm 2575:2579 arg1 freezability 2581:2592 good sperm freezability 2570:2592 good sperm freezability 2570:2592 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 17 61 theme identified 2407:2416 arg1 proteins 2428:2435 The identified candidate proteins 2403:2435 The identified candidate proteins 2403:2435 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 17 62 theme related 2486:2492 arg1 mechanism 2476:2484 the molecular mechanism 2462:2484 the molecular mechanism related to donkey sperm cryotolerance 2462:2522 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 4 63 theme proteins 550:557 arg1 total 536:540 A total 534:540 A total of 2682 proteins 534:557 A total of 2682 proteins were identified, among which 58 were significantly up-regulated in GFEs and 16 were down-regulated compared with PFEs. 36535622 13 64 theme freezability 1997:2008 arg1 differences 2010:2020 freezability differences 1997:2020 freezability differences 1997:2020 The mechanisms that affect the freezing difference in sperm quality remain to be investigated, and freezability differences was found to be related to protein composition of spermatozoa. 36535622 2 65 theme plasma 284:289 arg1 proteome 291:298 the seminal plasma proteome 272:298 the seminal plasma proteome 272:298 Our recent study shows that the freezability of donkey semen is related to the seminal plasma proteome. 36535622 1 66 theme cryopreservation 179:194 arg1 factor 163:168 a limiting factor 152:168 a limiting factor of sperm cryopreservation 152:194 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 1 66 theme cryopreservation 179:194 arg1 difference 112:121 The freezability difference 95:121 The freezability difference between donkey ejaculates 95:147 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 11 67 theme same 1780:1783 arg1 ejaculate 1785:1793 the same ejaculate 1776:1793 the same ejaculate 1776:1793 There are differences in sperm freezability reported to exist between or within breeds, and even between fractions coming from the same ejaculate. 36535622 17 68 theme donkey 2497:2502 arg1 cryotolerance 2510:2522 donkey sperm cryotolerance 2497:2522 donkey sperm cryotolerance 2497:2522 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 11 69 theme sperm 1674:1678 arg1 freezability 1680:1691 sperm freezability 1674:1691 sperm freezability reported to exist between or within breeds, and even between fractions coming from the same ejaculate 1674:1793 There are differences in sperm freezability reported to exist between or within breeds, and even between fractions coming from the same ejaculate. 36535622 5 70 theme biosynthetic 837:848 arg1 process 850:856 RNA biosynthetic process 833:856 RNA biosynthetic process 833:856 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 5 71 theme calcium 802:808 arg1 binding 810:816 calcium binding 802:816 calcium binding 802:816 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 8 72 theme candidate 1255:1263 arg1 proteins 1265:1272 The identified candidate proteins 1240:1272 The identified candidate proteins 1240:1272 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 5 73 theme Bioinformatic 678:690 arg1 results 701:707 Bioinformatic analysis results 678:707 Bioinformatic analysis results 678:707 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 2 74 theme semen 252:256 arg1 related 261:267 related 261:267 related 261:267 Our recent study shows that the freezability of donkey semen is related to the seminal plasma proteome. 36535622 2 74 theme semen 252:256 arg1 freezability 229:240 the freezability 225:240 the freezability of donkey semen 225:256 Our recent study shows that the freezability of donkey semen is related to the seminal plasma proteome. 36535622 8 75 used used 1283:1286 arg2 proteins 1265:1272 The identified candidate proteins 1240:1272 The identified candidate proteins 1240:1272 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 9 76 theme assisted 1490:1497 arg1 technology 1512:1521 assisted reproductive technology 1490:1521 assisted reproductive technology 1490:1521 SIGNIFICANCE: Cryopreserved semen has been widely used in assisted reproductive technology. 36535622 14 77 theme poor 2145:2148 arg1 semen 2163:2167 poor freezability semen 2145:2167 poor freezability semen 2145:2167 Some protein markers that can indicate good freezability or poor freezability semen have been identified in mammals. 36535622 13 78 theme freezing 1929:1936 arg1 difference 1938:1947 the freezing difference 1925:1947 the freezing difference in sperm quality 1925:1964 The mechanisms that affect the freezing difference in sperm quality remain to be investigated, and freezability differences was found to be related to protein composition of spermatozoa. 36535622 5 79 theme response 896:903 arg1 regulation 868:877 positive regulation 859:877 positive regulation of innate immune response 859:903 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 5 79 theme response 896:903 arg1 regulation 919:928 negative regulation 910:928 negative regulation of programmed cell death 910:953 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 5 79 theme response 896:903 arg1 regulation 819:828 regulation 819:828 regulation of RNA biosynthetic process 819:856 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 7 80 with ejaculates 1198:1207 arg1 freezabilities 1224:1237 different freezabilities 1214:1237 different freezabilities 1214:1237 Our study was the first to analyze the proteome of sperm from donkey ejaculates with different freezabilities. 36535622 16 81 theme semen 2345:2349 arg1 freezability 2351:2362 semen freezability 2345:2362 semen freezability 2345:2362 Additional novel biomarkers of semen freezability in donkey spermatozoa are also needed. 36535622 4 82 dep identified 564:573 arg1 up-regulated 610:621 up-regulated 610:621 were significantly up-regulated in GFEs 591:629 A total of 2682 proteins were identified, among which 58 were significantly up-regulated in GFEs and 16 were down-regulated compared with PFEs. 36535622 4 82 dep identified 564:573 arg1 down-regulated 643:656 down-regulated 643:656 were down-regulated compared with PFEs 638:675 A total of 2682 proteins were identified, among which 58 were significantly up-regulated in GFEs and 16 were down-regulated compared with PFEs. 36535622 1 83 theme limiting 154:161 arg1 factor 163:168 a limiting factor 152:168 a limiting factor of sperm cryopreservation 152:194 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 1 83 theme limiting 154:161 arg1 difference 112:121 The freezability difference 95:121 The freezability difference between donkey ejaculates 95:147 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 10 84 theme oxidative 1595:1603 arg1 stress 1605:1610 oxidative stress 1595:1610 oxidative stress 1595:1610 However, semen cryopreservation is a damaging process, which can cause oxidative stress, reduce sperm motility and motility. 36535622 8 85 theme molecular 1303:1311 arg1 mechanism 1313:1321 the molecular mechanism 1299:1321 the molecular mechanism related to donkey sperm cryotolerance 1299:1359 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 5 86 theme different 739:747 arg1 DAPs 769:772 DAPs 769:772 DAPs 769:772 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 5 86 theme different 739:747 arg1 proteins 759:766 different abundance proteins 739:766 different abundance proteins (DAPs) 739:773 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 14 87 theme freezability 2150:2161 arg1 semen 2163:2167 poor freezability semen 2145:2167 poor freezability semen 2145:2167 Some protein markers that can indicate good freezability or poor freezability semen have been identified in mammals. 36535622 8 88 theme related 1323:1329 arg1 mechanism 1313:1321 the molecular mechanism 1299:1321 the molecular mechanism related to donkey sperm cryotolerance 1299:1359 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 7 89 theme sperm 1180:1184 arg1 proteome 1168:1175 the proteome 1164:1175 the proteome of sperm from donkey ejaculates with different freezabilities 1164:1237 Our study was the first to analyze the proteome of sperm from donkey ejaculates with different freezabilities. 36535622 5 90 theme programmed 933:942 arg1 death 949:953 programmed cell death 933:953 programmed cell death 933:953 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 6 91 theme pathway 961:967 arg1 analysis 980:987 KEGG pathway enrichment analysis 956:987 KEGG pathway enrichment analysis 956:987 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 3 92 theme sperm 361:365 arg1 proteins 367:374 the different abundance sperm proteins 337:374 the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) 337:453 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 8 93 theme donkey 1334:1339 arg1 cryotolerance 1347:1359 donkey sperm cryotolerance 1334:1359 donkey sperm cryotolerance 1334:1359 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 5 94 theme death 949:953 arg1 regulation 868:877 positive regulation 859:877 positive regulation of innate immune response 859:903 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 5 94 theme death 949:953 arg1 regulation 919:928 negative regulation 910:928 negative regulation of programmed cell death 910:953 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 5 94 theme death 949:953 arg1 regulation 819:828 regulation 819:828 regulation of RNA biosynthetic process 819:856 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 9 95 used used 1482:1485 arg2 SIGNIFICANCE 1432:1443 SIGNIFICANCE 1432:1443 SIGNIFICANCE: Cryopreserved semen 1432:1464 SIGNIFICANCE: Cryopreserved semen has been widely used in assisted reproductive technology. 36535622 6 96 theme N-Glycan 1058:1065 arg1 biosynthesis 1067:1078 N-Glycan biosynthesis 1058:1078 N-Glycan biosynthesis 1058:1078 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 3 97 theme different 341:349 arg1 proteins 367:374 the different abundance sperm proteins 337:374 the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) 337:453 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 14 98 theme good 2124:2127 arg1 freezability 2129:2140 good freezability 2124:2140 good freezability 2124:2140 Some protein markers that can indicate good freezability or poor freezability semen have been identified in mammals. 36535622 0 99 theme comparative 10:20 arg1 analysis 32:39 TMT-based comparative proteomic analysis 0:39 TMT-based comparative proteomic analysis of Dezhou 0:49 TMT-based comparative proteomic analysis of Dezhou donkey spermatozoa related to freezability. 36535622 17 100 used used 2446:2449 arg2 proteins 2428:2435 The identified candidate proteins 2403:2435 The identified candidate proteins 2403:2435 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 3 101 theme freezability 384:395 arg1 GFEs 409:412 GFEs 409:412 GFEs 409:412 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 3 101 theme freezability 384:395 arg1 ejaculates 397:406 good freezability ejaculates 379:406 good freezability ejaculates (GFEs) 379:413 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 3 102 theme poor 419:422 arg1 PFEs 449:452 PFEs 449:452 PFEs 449:452 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 3 102 theme poor 419:422 arg1 ejaculates 437:446 poor freezability ejaculates 419:446 poor freezability ejaculates (PFEs) 419:453 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 12 103 theme cryopreservation 1880:1895 arg1 factor 1864:1869 a limiting factor 1853:1869 a limiting factor of sperm cryopreservation 1853:1895 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 12 103 theme cryopreservation 1880:1895 arg1 difference 1813:1822 The freezability difference 1796:1822 The freezability difference between donkey ejaculates 1796:1848 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 16 104 from biomarkers 2331:2340 arg1 spermatozoa 2374:2384 donkey spermatozoa 2367:2384 donkey spermatozoa 2367:2384 Additional novel biomarkers of semen freezability in donkey spermatozoa are also needed. 36535622 2 105 theme recent 201:206 arg1 study 208:212 Our recent study 197:212 Our recent study 197:212 Our recent study shows that the freezability of donkey semen is related to the seminal plasma proteome. 36535622 16 106 theme Additional 2314:2323 arg1 biomarkers 2331:2340 Additional novel biomarkers 2314:2340 Additional novel biomarkers of semen freezability in donkey spermatozoa 2314:2384 Additional novel biomarkers of semen freezability in donkey spermatozoa are also needed. 36535622 5 107 theme proteins 759:766 arg1 majority 727:734 the majority 723:734 the majority of different abundance proteins (DAPs) 723:773 Bioinformatic analysis results revealed that the majority of different abundance proteins (DAPs) participated in copper and calcium binding, regulation of RNA biosynthetic process, positive regulation of innate immune response, and negative regulation of programmed cell death. 36535622 6 108 theme GF 1025:1026 arg1 group 1028:1032 GF group 1025:1032 GF group 1025:1032 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 12 109 theme limiting 1855:1862 arg1 factor 1864:1869 a limiting factor 1853:1869 a limiting factor of sperm cryopreservation 1853:1895 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 12 109 theme limiting 1855:1862 arg1 difference 1813:1822 The freezability difference 1796:1822 The freezability difference between donkey ejaculates 1796:1848 The freezability difference between donkey ejaculates is a limiting factor of sperm cryopreservation. 36535622 10 110 dep cause 1589:1593 arg1 reduce 1613:1618 reduce 1613:1618 reduce sperm motility and motility 1613:1646 However, semen cryopreservation is a damaging process, which can cause oxidative stress, reduce sperm motility and motility. 36535622 11 111 from differences 1659:1669 arg1 freezability 1680:1691 sperm freezability 1674:1691 sperm freezability reported to exist between or within breeds, and even between fractions coming from the same ejaculate 1674:1793 There are differences in sperm freezability reported to exist between or within breeds, and even between fractions coming from the same ejaculate. 36535622 17 112 theme molecular 2466:2474 arg1 mechanism 2476:2484 the molecular mechanism 2462:2484 the molecular mechanism related to donkey sperm cryotolerance 2462:2522 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 10 113 theme semen 1533:1537 arg1 process 1570:1576 a damaging process 1559:1576 a damaging process 1559:1576 However, semen cryopreservation is a damaging process, which can cause oxidative stress, reduce sperm motility and motility. 36535622 10 113 theme semen 1533:1537 arg1 cryopreservation 1539:1554 semen cryopreservation 1533:1554 semen cryopreservation 1533:1554 However, semen cryopreservation is a damaging process, which can cause oxidative stress, reduce sperm motility and motility. 36535622 3 114 theme Tag 475:477 arg1 labeling 493:500 a Tandem Mass Tag (TMT) peptide labeling 461:500 a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach 461:531 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 15 115 theme donkey 2268:2273 arg1 proteome 2287:2294 donkey spermatozoa proteome 2268:2294 donkey spermatozoa proteome 2268:2294 Until now, there is no information about the relationship between donkey spermatozoa proteome and freezability. 36535622 6 116 theme endoplasmic 1106:1116 arg1 reticulum 1118:1126 endoplasmic reticulum 1106:1126 endoplasmic reticulum 1106:1126 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 8 117 theme sperm 1412:1416 arg1 freezability 1418:1429 good sperm freezability 1407:1429 good sperm freezability 1407:1429 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 3 118 theme Tandem 463:468 arg1 labeling 493:500 a Tandem Mass Tag (TMT) peptide labeling 461:500 a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach 461:531 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 36535622 17 119 theme jacks 2559:2563 arg1 screening 2546:2554 the screening 2542:2554 the screening of jacks with good sperm freezability 2542:2592 The identified candidate proteins might be used to explore the molecular mechanism related to donkey sperm cryotolerance and might improve the screening of jacks with good sperm freezability. 36535622 10 120 theme damaging 1561:1568 arg1 process 1570:1576 a damaging process 1559:1576 a damaging process 1559:1576 However, semen cryopreservation is a damaging process, which can cause oxidative stress, reduce sperm motility and motility. 36535622 10 120 theme damaging 1561:1568 arg1 cryopreservation 1539:1554 semen cryopreservation 1533:1554 semen cryopreservation 1533:1554 However, semen cryopreservation is a damaging process, which can cause oxidative stress, reduce sperm motility and motility. 36535622 6 121 from processing 1092:1101 arg1 reticulum 1118:1126 endoplasmic reticulum 1106:1126 endoplasmic reticulum 1106:1126 KEGG pathway enrichment analysis showed the up-regulated proteins in GF group were mainly involved in N-Glycan biosynthesis and protein processing in endoplasmic reticulum. 36535622 3 122 theme peptide 485:491 arg1 labeling 493:500 a Tandem Mass Tag (TMT) peptide labeling 461:500 a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach 461:531 In this study, we aimed to identify the different abundance sperm proteins in good freezability ejaculates (GFEs) and poor freezability ejaculates (PFEs) using a Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS approach. 35891376 2 0 from pathogens 404:412 arg1 role 374:377 a demonstrated role 359:377 a demonstrated role in protecting hosts from pathogens 359:412 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 0 from pathogens 404:412 arg1 hosts 393:397 protecting hosts 382:397 protecting hosts from pathogens 382:412 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 0 from pathogens 404:412 arg1 role 429:432 a possible role 418:432 a possible role in oral vaccine performance 418:460 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 10 1 theme composition 1486:1496 arg1 median 1500:1505 a pre-infection composition a median 1470:1505 a pre-infection composition a median of 58 days later 1470:1522 In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. 35891376 10 2 theme disruptive 1376:1385 arg1 AGE 1408:1410 disruptive norovirus-associated AGE 1376:1410 disruptive norovirus-associated AGE 1376:1410 In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. 35891376 4 3 theme infants 676:682 arg1 stools 661:666 the stools 657:666 the stools of five infants participating in a longitudinal birth cohort study conducted in León, Nicaragua 657:762 Metagenomic sequencing was performed on the stools of five infants participating in a longitudinal birth cohort study conducted in León, Nicaragua. 35891376 6 4 theme probiotic 978:986 arg1 species 988:994 probiotic species 978:994 probiotic species 978:994 Initially, the gut microbiomes resembled those of breastfeeding infants, rich in probiotic species. 35891376 7 5 theme Pseudomonas 1064:1074 arg1 species 1076:1082 Pseudomonas species 1064:1082 Pseudomonas species 1064:1082 When disturbed by AGE, Gammaproteobacteria dominated, particularly Pseudomonas species. 35891376 6 6 from species 988:994 arg1 rich 970:973 rich 970:973 rich 970:973 Initially, the gut microbiomes resembled those of breastfeeding infants, rich in probiotic species. 35891376 11 7 theme probiotic 1572:1580 arg1 treatments 1582:1591 probiotic treatments 1572:1591 probiotic treatments 1572:1591 Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. 35891376 2 8 theme microbiome 330:339 arg1 health 341:346 infant gut microbiome health 319:346 infant gut microbiome health 319:346 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 8 9 theme glycan 1165:1170 arg1 biosynthesis 1172:1183 glycan biosynthesis 1165:1183 glycan biosynthesis 1165:1183 Alpha diversity increased but the genes involved in carbohydrate metabolism and glycan biosynthesis decreased. 35891376 3 10 theme microbiome 506:515 arg1 changes 517:523 infant gut microbiome changes 495:523 infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) 495:587 In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. 35891376 6 11 theme rich 970:973 arg1 infants 961:967 breastfeeding infants 947:967 breastfeeding infants 947:967 Initially, the gut microbiomes resembled those of breastfeeding infants, rich in probiotic species. 35891376 3 12 theme norovirus-associated 540:559 arg1 AGE 584:586 AGE 584:586 AGE 584:586 In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. 35891376 3 12 theme norovirus-associated 540:559 arg1 gastroenteritis 567:581 norovirus-associated acute gastroenteritis 540:581 norovirus-associated acute gastroenteritis (AGE) 540:587 In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. 35891376 9 13 theme pre-infection 1327:1339 arg1 microbiomes 1341:1351 the pre-infection microbiomes 1323:1351 the pre-infection microbiomes 1323:1351 After the symptoms subsided, the gut microbiomes rebounded with their taxonomic and functional communities resembling those of the pre-infection microbiomes. 35891376 10 14 theme gut 1417:1419 arg1 microbiome 1421:1430 the gut microbiome 1413:1430 the gut microbiome 1413:1430 In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. 35891376 0 15 theme Birth 109:113 arg1 Cohort 115:120 a Longitudinal Birth Cohort 94:120 a Longitudinal Birth Cohort in Leon, Nicaragua 94:139 Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants Enrolled in a Longitudinal Birth Cohort in Leon, Nicaragua. 35891376 2 16 from role 429:432 arg1 performance 450:460 oral vaccine performance 437:460 oral vaccine performance 437:460 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 16 from role 429:432 arg1 hosts 393:397 protecting hosts 382:397 protecting hosts from pathogens 382:412 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 16 from role 429:432 arg1 pathogens 404:412 pathogens 404:412 pathogens 404:412 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 6 17 from rich 970:973 arg1 species 988:994 probiotic species 978:994 probiotic species 978:994 Initially, the gut microbiomes resembled those of breastfeeding infants, rich in probiotic species. 35891376 4 18 theme cohort 722:727 arg1 study 729:733 a longitudinal birth cohort study 701:733 a longitudinal birth cohort study conducted in León, Nicaragua 701:762 Metagenomic sequencing was performed on the stools of five infants participating in a longitudinal birth cohort study conducted in León, Nicaragua. 35891376 3 19 theme infant 495:500 arg1 changes 517:523 infant gut microbiome changes 495:523 infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) 495:587 In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. 35891376 0 20 theme Longitudinal 96:107 arg1 Cohort 115:120 a Longitudinal Birth Cohort 94:120 a Longitudinal Birth Cohort in Leon, Nicaragua 94:139 Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants Enrolled in a Longitudinal Birth Cohort in Leon, Nicaragua. 35891376 11 21 theme gut 1686:1688 arg1 microbiome 1690:1699 the infant gut microbiome 1675:1699 the infant gut microbiome 1675:1699 Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. 35891376 2 22 theme vaccine 442:448 arg1 performance 450:460 oral vaccine performance 437:460 oral vaccine performance 437:460 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 10 23 theme days 1513:1516 arg1 median 1500:1505 a pre-infection composition a median 1470:1505 a pre-infection composition a median of 58 days later 1470:1522 In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. 35891376 3 24 theme gut 502:504 arg1 changes 517:523 infant gut microbiome changes 495:523 infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) 495:587 In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. 35891376 11 25 dep role 1633:1636 arg1 have 1659:1662 have 1659:1662 have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness 1659:1774 Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. 35891376 2 26 theme demonstrated 361:372 arg1 role 374:377 a demonstrated role 359:377 a demonstrated role in protecting hosts from pathogens 359:412 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 0 27 theme Microbiome 4:13 arg1 Changes 15:21 Gut Microbiome Changes 0:21 Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants 0:80 Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants Enrolled in a Longitudinal Birth Cohort in Leon, Nicaragua. 35891376 8 28 theme carbohydrate 1137:1148 arg1 metabolism 1150:1159 carbohydrate metabolism 1137:1159 carbohydrate metabolism 1137:1159 Alpha diversity increased but the genes involved in carbohydrate metabolism and glycan biosynthesis decreased. 35891376 2 29 theme norovirus 296:304 arg1 infection 306:314 norovirus infection 296:314 norovirus infection 296:314 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 0 30 theme Gut 0:2 arg1 Changes 15:21 Gut Microbiome Changes 0:21 Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants 0:80 Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants Enrolled in a Longitudinal Birth Cohort in Leon, Nicaragua. 35891376 8 31 theme Alpha 1085:1089 arg1 diversity 1091:1099 Alpha diversity 1085:1099 Alpha diversity 1085:1099 Alpha diversity increased but the genes involved in carbohydrate metabolism and glycan biosynthesis decreased. 35891376 10 32 theme a 1498:1498 arg1 median 1500:1505 a pre-infection composition a median 1470:1505 a pre-infection composition a median of 58 days later 1470:1522 In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. 35891376 3 33 theme acute 561:565 arg1 AGE 584:586 AGE 584:586 AGE 584:586 In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. 35891376 3 33 theme acute 561:565 arg1 gastroenteritis 567:581 norovirus-associated acute gastroenteritis 540:581 norovirus-associated acute gastroenteritis (AGE) 540:587 In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. 35891376 10 34 theme pre-infection 1472:1484 arg1 median 1500:1505 a pre-infection composition a median 1470:1505 a pre-infection composition a median of 58 days later 1470:1522 In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. 35891376 5 35 theme gut 805:807 arg1 microbiomes 809:819 gut microbiomes 805:819 gut microbiomes 805:819 Taxonomic and functional diversities of gut microbiomes were profiled at time points before, during, and after norovirus infection. 35891376 6 36 theme breastfeeding 947:959 arg1 infants 961:967 breastfeeding infants 947:967 breastfeeding infants 947:967 Initially, the gut microbiomes resembled those of breastfeeding infants, rich in probiotic species. 35891376 9 37 theme gut 1229:1231 arg1 microbiomes 1233:1243 the gut microbiomes 1225:1243 the gut microbiomes 1225:1243 After the symptoms subsided, the gut microbiomes rebounded with their taxonomic and functional communities resembling those of the pre-infection microbiomes. 35891376 4 38 theme birth 716:720 arg1 study 729:733 a longitudinal birth cohort study 701:733 a longitudinal birth cohort study conducted in León, Nicaragua 701:762 Metagenomic sequencing was performed on the stools of five infants participating in a longitudinal birth cohort study conducted in León, Nicaragua. 35891376 2 39 from role 374:377 arg1 performance 450:460 oral vaccine performance 437:460 oral vaccine performance 437:460 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 39 from role 374:377 arg1 hosts 393:397 protecting hosts 382:397 protecting hosts from pathogens 382:412 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 39 from role 374:377 arg1 pathogens 404:412 pathogens 404:412 pathogens 404:412 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 40 contain has 355:357 arg1 health 341:346 infant gut microbiome health 319:346 infant gut microbiome health 319:346 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 40 contain has 355:357 arg2 role 374:377 a demonstrated role 359:377 a demonstrated role in protecting hosts from pathogens 359:412 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 40 contain has 355:357 arg2 role 429:432 a possible role 418:432 a possible role in oral vaccine performance 418:460 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 5 41 theme norovirus 876:884 arg1 infection 886:894 norovirus infection 876:894 norovirus infection 876:894 Taxonomic and functional diversities of gut microbiomes were profiled at time points before, during, and after norovirus infection. 35891376 1 42 theme diarrheal 187:195 arg1 illnesses 197:205 diarrheal illnesses 187:205 diarrheal illnesses 187:205 Noroviruses are associated with one fifth of diarrheal illnesses globally and are not yet preventable with vaccines. 35891376 0 43 theme Norovirus 38:46 arg1 Infection 48:56 Norovirus Infection 38:56 Norovirus Infection 38:56 Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants Enrolled in a Longitudinal Birth Cohort in Leon, Nicaragua. 35891376 1 44 theme illnesses 197:205 arg1 fifth 178:182 fifth 178:182 fifth 178:182 Noroviruses are associated with one fifth of diarrheal illnesses globally and are not yet preventable with vaccines. 35891376 2 45 theme protecting 382:391 arg1 hosts 393:397 protecting hosts 382:397 protecting hosts from pathogens 382:412 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 46 theme oral 437:440 arg1 performance 450:460 oral vaccine performance 437:460 oral vaccine performance 437:460 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 5 47 theme Taxonomic 765:773 arg1 diversities 790:800 Taxonomic and functional diversities 765:800 Taxonomic and functional diversities of gut microbiomes 765:819 Taxonomic and functional diversities of gut microbiomes were profiled at time points before, during, and after norovirus infection. 35891376 3 48 theme recovery 607:614 arg1 changes 517:523 infant gut microbiome changes 495:523 infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) 495:587 In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. 35891376 3 48 theme recovery 607:614 arg1 extent 597:602 the extent 593:602 the extent of recovery 593:614 In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. 35891376 11 49 theme role 1633:1636 arg1 understanding 1612:1624 our understanding 1608:1624 our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness 1608:1774 Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. 35891376 4 50 theme Metagenomic 617:627 arg1 sequencing 629:638 Metagenomic sequencing 617:638 Metagenomic sequencing 617:638 Metagenomic sequencing was performed on the stools of five infants participating in a longitudinal birth cohort study conducted in León, Nicaragua. 35891376 2 51 theme gut 326:328 arg1 health 341:346 infant gut microbiome health 319:346 infant gut microbiome health 319:346 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 5 52 theme functional 779:788 arg1 diversities 790:800 Taxonomic and functional diversities 765:800 Taxonomic and functional diversities of gut microbiomes 765:819 Taxonomic and functional diversities of gut microbiomes were profiled at time points before, during, and after norovirus infection. 35891376 6 53 theme gut 912:914 arg1 microbiomes 916:926 the gut microbiomes 908:926 the gut microbiomes 908:926 Initially, the gut microbiomes resembled those of breastfeeding infants, rich in probiotic species. 35891376 9 54 theme taxonomic 1266:1274 arg1 communities 1291:1301 their taxonomic and functional communities 1260:1301 their taxonomic and functional communities resembling those of the pre-infection microbiomes 1260:1351 After the symptoms subsided, the gut microbiomes rebounded with their taxonomic and functional communities resembling those of the pre-infection microbiomes. 35891376 1 55 with preventable 232:242 arg1 vaccines 249:256 vaccines 249:256 vaccines 249:256 Noroviruses are associated with one fifth of diarrheal illnesses globally and are not yet preventable with vaccines. 35891376 2 56 theme infant 319:324 arg1 health 341:346 infant gut microbiome health 319:346 infant gut microbiome health 319:346 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 11 57 theme long-term 1708:1716 arg1 outcomes 1718:1725 their long-term outcomes 1702:1725 their long-term outcomes 1702:1725 Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. 35891376 11 58 theme vaccine 1754:1760 arg1 effectiveness 1762:1774 oral vaccine effectiveness 1749:1774 oral vaccine effectiveness 1749:1774 Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. 35891376 4 59 theme longitudinal 703:714 arg1 study 729:733 a longitudinal birth cohort study 701:733 a longitudinal birth cohort study conducted in León, Nicaragua 701:762 Metagenomic sequencing was performed on the stools of five infants participating in a longitudinal birth cohort study conducted in León, Nicaragua. 35891376 11 60 theme oral 1749:1752 arg1 effectiveness 1762:1774 oral vaccine effectiveness 1749:1774 oral vaccine effectiveness 1749:1774 Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. 35891376 9 61 theme functional 1280:1289 arg1 communities 1291:1301 their taxonomic and functional communities 1260:1301 their taxonomic and functional communities resembling those of the pre-infection microbiomes 1260:1351 After the symptoms subsided, the gut microbiomes rebounded with their taxonomic and functional communities resembling those of the pre-infection microbiomes. 35891376 11 62 theme AGE 1655:1657 arg1 episodes 1643:1650 episodes 1643:1650 episodes of AGE 1643:1657 Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. 35891376 2 63 theme infection 306:314 arg1 effects 285:291 the effects 281:291 the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance 281:460 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 11 64 theme infant 1679:1684 arg1 microbiome 1690:1699 the infant gut microbiome 1675:1699 the infant gut microbiome 1675:1699 Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. 35891376 5 65 theme time 838:841 arg1 points 843:848 time points 838:848 time points 838:848 Taxonomic and functional diversities of gut microbiomes were profiled at time points before, during, and after norovirus infection. 35891376 11 66 theme new 1544:1546 arg1 insights 1548:1555 new insights 1544:1555 new insights 1544:1555 Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. 35891376 5 67 theme microbiomes 809:819 arg1 diversities 790:800 Taxonomic and functional diversities 765:800 Taxonomic and functional diversities of gut microbiomes 765:819 Taxonomic and functional diversities of gut microbiomes were profiled at time points before, during, and after norovirus infection. 35891376 10 68 theme norovirus-associated 1387:1406 arg1 AGE 1408:1410 disruptive norovirus-associated AGE 1376:1410 disruptive norovirus-associated AGE 1376:1410 In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. 35891376 2 69 theme possible 420:427 arg1 role 429:432 a possible role 418:432 a possible role in oral vaccine performance 418:460 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 2 70 from effects 285:291 arg1 health 341:346 infant gut microbiome health 319:346 infant gut microbiome health 319:346 Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. 35891376 0 71 from Cohort 115:120 arg1 Nicaragua 131:139 Nicaragua 131:139 Nicaragua 131:139 Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants Enrolled in a Longitudinal Birth Cohort in Leon, Nicaragua. 36297421 13 0 theme surface 1900:1906 arg1 SPR 1927:1929 SPR 1927:1929 SPR 1927:1929 We also analyzed the binding of mAbs to FcγR by surface plasmon resonance (SPR) and the glycan composition. 36297421 13 0 theme surface 1900:1906 arg1 resonance 1916:1924 surface plasmon resonance 1900:1924 surface plasmon resonance (SPR) 1900:1930 We also analyzed the binding of mAbs to FcγR by surface plasmon resonance (SPR) and the glycan composition. 36297421 9 1 from viability 1432:1440 arg1 measurement 1472:1482 titer measurement 1466:1482 titer measurement 1466:1482 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 9 1 from viability 1432:1440 arg1 culture 1457:1463 a fed-batch culture 1445:1463 a fed-batch culture 1445:1463 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 9 1 from viability 1432:1440 arg1 estimation 1511:1520 specific productivity estimation 1489:1520 specific productivity estimation 1489:1520 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 0 2 theme Cell 93:96 arg1 Lines 98:102 Stable Cell Lines 86:102 Stable Cell Lines 86:102 Characterization of Neutralizing Human Anti-Tetanus Monoclonal Antibodies Produced by Stable Cell Lines. 36297421 13 3 theme plasmon 1908:1914 arg1 SPR 1927:1929 SPR 1927:1929 SPR 1927:1929 We also analyzed the binding of mAbs to FcγR by surface plasmon resonance (SPR) and the glycan composition. 36297421 13 3 theme plasmon 1908:1914 arg1 resonance 1916:1924 surface plasmon resonance 1900:1924 surface plasmon resonance (SPR) 1900:1930 We also analyzed the binding of mAbs to FcγR by surface plasmon resonance (SPR) and the glycan composition. 36297421 2 4 theme variable 323:330 arg1 responses 332:340 variable responses 323:340 variable responses to vaccines 323:352 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 9 5 theme specific 1489:1496 arg1 estimation 1511:1520 specific productivity estimation 1489:1520 specific productivity estimation 1489:1520 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 6 6 from receptor 964:971 arg1 neurons 976:982 neurons 976:982 neurons 976:982 We also identified two mAbs that can impair the binding of TeNT to the GT1b ganglioside receptor in neurons. 36297421 7 7 theme B 1195:1195 arg1 cells 1197:1201 human B cells 1189:1201 human B cells 1189:1201 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 9 8 from growth 1421:1426 arg1 measurement 1472:1482 titer measurement 1466:1482 titer measurement 1466:1482 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 9 8 from growth 1421:1426 arg1 culture 1457:1463 a fed-batch culture 1445:1463 a fed-batch culture 1445:1463 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 9 8 from growth 1421:1426 arg1 estimation 1511:1520 specific productivity estimation 1489:1520 specific productivity estimation 1489:1520 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 7 9 theme variable 1149:1156 arg1 regions 1158:1164 the paired variable regions 1138:1164 the paired variable regions resulting from PCRs of human B cells 1138:1201 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 7 10 theme lines 1028:1032 arg1 series 1013:1018 a series 1011:1018 a series of cell lines 1011:1032 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 14 11 theme anti-tetanus 2017:2028 arg1 mAb 2030:2032 an anti-tetanus mAb 2014:2032 an anti-tetanus mAb 2014:2032 Molecular docking analyses showed the binding site of an anti-tetanus mAb. 36297421 13 12 theme mAbs 1884:1887 arg1 binding 1873:1879 the binding 1869:1879 the binding of mAbs to FcγR 1869:1895 We also analyzed the binding of mAbs to FcγR by surface plasmon resonance (SPR) and the glycan composition. 36297421 6 13 theme GT1b 947:950 arg1 receptor 964:971 the GT1b ganglioside receptor 943:971 the GT1b ganglioside receptor in neurons 943:982 We also identified two mAbs that can impair the binding of TeNT to the GT1b ganglioside receptor in neurons. 36297421 6 14 theme TeNT 935:938 arg1 binding 924:930 the binding 920:930 the binding of TeNT to the GT1b ganglioside receptor in neurons 920:982 We also identified two mAbs that can impair the binding of TeNT to the GT1b ganglioside receptor in neurons. 36297421 11 15 theme toxin 1744:1748 arg1 binding 1750:1756 toxin binding 1744:1756 toxin binding to GT1b 1744:1764 The binding of mAbs to TeNT was confirmed by ELISA and inhibition of toxin binding to GT1b. 36297421 5 16 theme different 787:795 arg1 sites 797:801 different sites 787:801 different sites of TeNT 787:809 We identified a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice. 36297421 5 16 theme different 787:795 arg1 TeNT 806:809 TeNT 806:809 TeNT 806:809 We identified a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice. 36297421 7 17 theme cell 1023:1026 arg1 lines 1028:1032 cell lines 1023:1032 cell lines 1023:1032 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 10 18 theme mAbs 1548:1551 arg1 affinity 1527:1534 The affinity 1523:1534 The affinity of purified mAbs 1523:1551 The affinity of purified mAbs was analyzed by kinetics and under steady-state conditions, as three mAbs could not dissociate from TeNT within 36,000 s. 36297421 5 19 theme preclinical 727:737 arg1 assay 739:743 a preclinical assay 725:743 a preclinical assay 725:743 We identified a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice. 36297421 5 20 from symptoms 848:855 arg1 mice 870:873 mice 870:873 mice 870:873 We identified a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice. 36297421 14 21 theme binding 1998:2004 arg1 mAb 2030:2032 an anti-tetanus mAb 2014:2032 an anti-tetanus mAb 2014:2032 Molecular docking analyses showed the binding site of an anti-tetanus mAb. 36297421 14 21 theme binding 1998:2004 arg1 site 2006:2009 the binding site 1994:2009 the binding site of an anti-tetanus mAb 1994:2032 Molecular docking analyses showed the binding site of an anti-tetanus mAb. 36297421 2 22 theme immunocompromised 361:377 arg1 status 379:384 immunocompromised status 361:384 immunocompromised status 361:384 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 12 23 theme individual 1809:1818 arg1 contribution 1824:1835 the individual mAb contribution 1805:1835 the individual mAb contribution to inhibition 1805:1849 The use of the mAbs mixture confirmed the individual mAb contribution to inhibition. 36297421 7 24 theme constant 1104:1111 arg1 regions 1113:1119 constant regions 1104:1119 constant regions 1104:1119 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 3 25 from countries 476:484 arg1 prevalent 440:448 prevalent 440:448 prevalent 440:448 Tetanus is most prevalent in low- and medium-income countries, where it remains a health problem. 36297421 8 26 theme cell 1237:1240 arg1 lines 1242:1246 stable cell lines 1230:1246 stable cell lines for five mAbs 1230:1260 In this way, we generated stable cell lines for five mAbs and compared and characterized the antibody produced in large quantities, enabling the characterization experiments. 36297421 7 27 theme cells 1197:1201 arg1 PCRs 1181:1184 PCRs 1181:1184 PCRs of human B cells 1181:1201 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 12 28 theme mixture 1787:1793 arg1 use 1771:1773 The use 1767:1773 The use of the mAbs mixture 1767:1793 The use of the mAbs mixture confirmed the individual mAb contribution to inhibition. 36297421 7 29 contain containing 1058:1067 arg2 sequences 1069:1077 sequences 1069:1077 sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells 1069:1201 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 7 29 contain containing 1058:1067 arg1 vectors 1050:1056 vectors 1050:1056 vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells 1050:1201 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 1 30 theme Tetanus 105:111 arg1 TeNT 120:123 TeNT 120:123 TeNT 120:123 Tetanus toxin (TeNT) is produced by C. tetani, a spore-forming bacillus broadly spread in the environment. 36297421 1 30 theme Tetanus 105:111 arg1 toxin 113:117 Tetanus toxin 105:117 Tetanus toxin (TeNT) 105:124 Tetanus toxin (TeNT) is produced by C. tetani, a spore-forming bacillus broadly spread in the environment. 36297421 5 31 theme TeNT 806:809 arg1 sites 797:801 different sites 787:801 different sites of TeNT 787:809 We identified a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice. 36297421 5 31 theme TeNT 806:809 arg1 TeNT 806:809 TeNT 806:809 TeNT 806:809 We identified a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice. 36297421 0 32 theme Human 33:37 arg1 Antibodies 63:72 Neutralizing Human Anti-Tetanus Monoclonal Antibodies 20:72 Neutralizing Human Anti-Tetanus Monoclonal Antibodies 20:72 Characterization of Neutralizing Human Anti-Tetanus Monoclonal Antibodies Produced by Stable Cell Lines. 36297421 9 33 theme productivity 1498:1509 arg1 estimation 1511:1520 specific productivity estimation 1489:1520 specific productivity estimation 1489:1520 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 9 34 theme fed-batch 1447:1455 arg1 culture 1457:1463 a fed-batch culture 1445:1463 a fed-batch culture 1445:1463 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 3 35 theme low- 453:456 arg1 countries 476:484 low- and medium-income countries 453:484 low- and medium-income countries 453:484 Tetanus is most prevalent in low- and medium-income countries, where it remains a health problem. 36297421 0 36 theme Neutralizing 20:31 arg1 Antibodies 63:72 Neutralizing Human Anti-Tetanus Monoclonal Antibodies 20:72 Neutralizing Human Anti-Tetanus Monoclonal Antibodies 20:72 Characterization of Neutralizing Human Anti-Tetanus Monoclonal Antibodies Produced by Stable Cell Lines. 36297421 14 37 theme Molecular 1960:1968 arg1 analyses 1978:1985 Molecular docking analyses 1960:1985 Molecular docking analyses 1960:1985 Molecular docking analyses showed the binding site of an anti-tetanus mAb. 36297421 10 38 theme steady-state 1588:1599 arg1 conditions 1601:1610 steady-state conditions 1588:1610 steady-state conditions 1588:1610 The affinity of purified mAbs was analyzed by kinetics and under steady-state conditions, as three mAbs could not dissociate from TeNT within 36,000 s. 36297421 2 39 theme immune 403:408 arg1 surveillance 410:421 age-decreased immune surveillance 389:421 age-decreased immune surveillance 389:421 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 0 40 theme Monoclonal 52:61 arg1 Antibodies 63:72 Neutralizing Human Anti-Tetanus Monoclonal Antibodies 20:72 Neutralizing Human Anti-Tetanus Monoclonal Antibodies 20:72 Characterization of Neutralizing Human Anti-Tetanus Monoclonal Antibodies Produced by Stable Cell Lines. 36297421 4 41 theme tetani 623:628 arg1 infection 630:638 C. tetani infection 620:638 C. tetani infection 620:638 Neutralizing monoclonal antibodies (mAbs) can prevent the severity of illness and death caused by C. tetani infection. 36297421 2 42 theme inexpensive 224:234 arg1 available 256:264 available 256:264 available 256:264 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 2 42 theme inexpensive 224:234 arg1 vaccine 245:251 an inexpensive and safe vaccine 221:251 an inexpensive and safe vaccine 221:251 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 11 43 theme binding 1750:1756 arg1 inhibition 1730:1739 inhibition 1730:1739 inhibition 1730:1739 The binding of mAbs to TeNT was confirmed by ELISA and inhibition of toxin binding to GT1b. 36297421 11 43 theme binding 1750:1756 arg1 ELISA 1720:1724 ELISA 1720:1724 ELISA 1720:1724 The binding of mAbs to TeNT was confirmed by ELISA and inhibition of toxin binding to GT1b. 36297421 2 44 theme age-decreased 389:401 arg1 surveillance 410:421 age-decreased immune surveillance 389:421 age-decreased immune surveillance 389:421 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 0 45 theme Anti-Tetanus 39:50 arg1 Antibodies 63:72 Neutralizing Human Anti-Tetanus Monoclonal Antibodies 20:72 Neutralizing Human Anti-Tetanus Monoclonal Antibodies 20:72 Characterization of Neutralizing Human Anti-Tetanus Monoclonal Antibodies Produced by Stable Cell Lines. 36297421 11 46 theme mAbs 1690:1693 arg1 binding 1679:1685 The binding 1675:1685 The binding of mAbs to TeNT 1675:1701 The binding of mAbs to TeNT was confirmed by ELISA and inhibition of toxin binding to GT1b. 36297421 9 47 theme titer 1466:1470 arg1 measurement 1472:1482 titer measurement 1466:1482 titer measurement 1466:1482 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 3 48 from prevalent 440:448 arg1 countries 476:484 low- and medium-income countries 453:484 low- and medium-income countries 453:484 Tetanus is most prevalent in low- and medium-income countries, where it remains a health problem. 36297421 4 49 theme C. 620:621 arg1 infection 630:638 C. tetani infection 620:638 C. tetani infection 620:638 Neutralizing monoclonal antibodies (mAbs) can prevent the severity of illness and death caused by C. tetani infection. 36297421 14 50 theme docking 1970:1976 arg1 analyses 1978:1985 Molecular docking analyses 1960:1985 Molecular docking analyses 1960:1985 Molecular docking analyses showed the binding site of an anti-tetanus mAb. 36297421 8 51 theme large 1318:1322 arg1 quantities 1324:1333 large quantities 1318:1333 large quantities 1318:1333 In this way, we generated stable cell lines for five mAbs and compared and characterized the antibody produced in large quantities, enabling the characterization experiments. 36297421 8 52 theme stable 1230:1235 arg1 lines 1242:1246 stable cell lines 1230:1246 stable cell lines for five mAbs 1230:1260 In this way, we generated stable cell lines for five mAbs and compared and characterized the antibody produced in large quantities, enabling the characterization experiments. 36297421 0 53 theme Antibodies 63:72 arg1 Characterization 0:15 Characterization 0:15 Characterization of Neutralizing Human Anti-Tetanus Monoclonal Antibodies 0:72 Characterization of Neutralizing Human Anti-Tetanus Monoclonal Antibodies Produced by Stable Cell Lines. 36297421 4 54 theme monoclonal 535:544 arg1 mAbs 558:561 mAbs 558:561 mAbs 558:561 Neutralizing monoclonal antibodies (mAbs) can prevent the severity of illness and death caused by C. tetani infection. 36297421 4 54 theme monoclonal 535:544 arg1 antibodies 546:555 Neutralizing monoclonal antibodies 522:555 Neutralizing monoclonal antibodies (mAbs) 522:562 Neutralizing monoclonal antibodies (mAbs) can prevent the severity of illness and death caused by C. tetani infection. 36297421 9 55 theme cell 1416:1419 arg1 growth 1421:1426 cell growth 1416:1426 cell growth 1416:1426 We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. 36297421 2 56 theme shots 313:317 arg1 responses 332:340 variable responses 323:340 variable responses to vaccines 323:352 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 2 56 theme shots 313:317 arg1 lack 297:300 a lack 295:300 a lack of booster shots 295:317 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 4 57 theme Neutralizing 522:533 arg1 mAbs 558:561 mAbs 558:561 mAbs 558:561 Neutralizing monoclonal antibodies (mAbs) can prevent the severity of illness and death caused by C. tetani infection. 36297421 4 57 theme Neutralizing 522:533 arg1 antibodies 546:555 Neutralizing monoclonal antibodies 522:555 Neutralizing monoclonal antibodies (mAbs) 522:562 Neutralizing monoclonal antibodies (mAbs) can prevent the severity of illness and death caused by C. tetani infection. 36297421 7 58 dep heavy 1088:1092 arg1 regions 1113:1119 constant regions 1104:1119 constant regions 1104:1119 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 7 59 theme paired 1142:1147 arg1 regions 1158:1164 the paired variable regions 1138:1164 the paired variable regions resulting from PCRs of human B cells 1138:1201 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 2 60 theme booster 305:311 arg1 shots 313:317 booster shots 305:317 booster shots 305:317 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 4 61 theme illness 592:598 arg1 severity 580:587 the severity 576:587 the severity of illness and death caused by C. tetani infection 576:638 Neutralizing monoclonal antibodies (mAbs) can prevent the severity of illness and death caused by C. tetani infection. 36297421 5 62 theme mAbs 666:669 arg1 panel 657:661 a panel 655:661 a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice 655:873 We identified a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice. 36297421 8 63 theme characterization 1349:1364 arg1 experiments 1366:1376 the characterization experiments 1345:1376 the characterization experiments 1345:1376 In this way, we generated stable cell lines for five mAbs and compared and characterized the antibody produced in large quantities, enabling the characterization experiments. 36297421 6 64 theme ganglioside 952:962 arg1 receptor 964:971 the GT1b ganglioside receptor 943:971 the GT1b ganglioside receptor in neurons 943:982 We also identified two mAbs that can impair the binding of TeNT to the GT1b ganglioside receptor in neurons. 36297421 1 65 theme C. 141:142 arg1 bacillus 168:175 a spore-forming bacillus 152:175 a spore-forming bacillus broadly spread in the environment 152:209 Tetanus toxin (TeNT) is produced by C. tetani, a spore-forming bacillus broadly spread in the environment. 36297421 1 65 theme C. 141:142 arg1 tetani 144:149 C. tetani 141:149 C. tetani 141:149 Tetanus toxin (TeNT) is produced by C. tetani, a spore-forming bacillus broadly spread in the environment. 36297421 5 66 from death 861:865 arg1 mice 870:873 mice 870:873 mice 870:873 We identified a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice. 36297421 3 67 theme medium-income 462:474 arg1 countries 476:484 low- and medium-income countries 453:484 low- and medium-income countries 453:484 Tetanus is most prevalent in low- and medium-income countries, where it remains a health problem. 36297421 0 68 theme Stable 86:91 arg1 Lines 98:102 Stable Cell Lines 86:102 Stable Cell Lines 86:102 Characterization of Neutralizing Human Anti-Tetanus Monoclonal Antibodies Produced by Stable Cell Lines. 36297421 10 69 theme purified 1539:1546 arg1 mAbs 1548:1551 purified mAbs 1539:1551 purified mAbs 1539:1551 The affinity of purified mAbs was analyzed by kinetics and under steady-state conditions, as three mAbs could not dissociate from TeNT within 36,000 s. 36297421 2 70 theme safe 240:243 arg1 available 256:264 available 256:264 available 256:264 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 2 70 theme safe 240:243 arg1 vaccine 245:251 an inexpensive and safe vaccine 221:251 an inexpensive and safe vaccine 221:251 Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. 36297421 5 71 theme mAbs 769:772 arg1 trio 761:764 a trio 759:764 a trio of mAbs that bind to different sites of TeNT 759:809 We identified a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice. 36297421 7 72 theme human 1189:1193 arg1 cells 1197:1201 human B cells 1189:1201 human B cells 1189:1201 In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. 36297421 4 73 theme death 604:608 arg1 severity 580:587 the severity 576:587 the severity of illness and death caused by C. tetani infection 576:638 Neutralizing monoclonal antibodies (mAbs) can prevent the severity of illness and death caused by C. tetani infection. 36297421 12 74 theme mAb 1820:1822 arg1 contribution 1824:1835 the individual mAb contribution 1805:1835 the individual mAb contribution to inhibition 1805:1849 The use of the mAbs mixture confirmed the individual mAb contribution to inhibition. 36297421 12 75 theme mAbs 1782:1785 arg1 mixture 1787:1793 the mAbs mixture 1778:1793 the mAbs mixture 1778:1793 The use of the mAbs mixture confirmed the individual mAb contribution to inhibition. 36297421 3 76 theme health 506:511 arg1 problem 513:519 a health problem 504:519 a health problem 504:519 Tetanus is most prevalent in low- and medium-income countries, where it remains a health problem. 36297421 13 77 theme glycan 1940:1945 arg1 composition 1947:1957 the glycan composition 1936:1957 the glycan composition 1936:1957 We also analyzed the binding of mAbs to FcγR by surface plasmon resonance (SPR) and the glycan composition. 36297421 14 78 theme mAb 2030:2032 arg1 mAb 2030:2032 an anti-tetanus mAb 2014:2032 an anti-tetanus mAb 2014:2032 Molecular docking analyses showed the binding site of an anti-tetanus mAb. 36297421 14 78 theme mAb 2030:2032 arg1 site 2006:2009 the binding site 1994:2009 the binding site of an anti-tetanus mAb 1994:2032 Molecular docking analyses showed the binding site of an anti-tetanus mAb. 36448434 8 0 theme Lectin 1142:1147 arg1 histochemistry 1149:1162 Lectin histochemistry 1142:1162 Lectin histochemistry 1142:1162 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 4 1 theme Korean 571:576 arg1 cattle 585:590 adult Korean native cattle 565:590 adult Korean native cattle 565:590 METHODS The OM of neonate and adult Korean native cattle was evaluated using histological, immunohistochemical, and lectin histochemical methods. 36448434 10 2 dep CONCLUSIONS 1618:1628 arg1 This 1630:1633 This 1630:1633 This 1630:1633 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 10 2 dep CONCLUSIONS 1618:1628 arg1 study 1648:1652 the first study 1638:1652 the first study 1638:1652 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 6 3 theme periodic 821:828 arg1 pH 859:860 pH 2.5 859:864 pH 2.5 859:864 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 6 3 theme periodic 821:828 arg1 Schiff 835:840 periodic acid Schiff 821:840 periodic acid Schiff 821:840 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 10 4 theme native 1715:1720 arg1 cattle 1722:1727 Korean native cattle 1708:1727 Korean native cattle with a focus on lectin histochemistry 1708:1765 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 4 5 theme cattle 585:590 arg1 OM 547:548 The OM 543:548 METHODS The OM of neonate and adult Korean native cattle 535:590 METHODS The OM of neonate and adult Korean native cattle was evaluated using histological, immunohistochemical, and lectin histochemical methods. 36448434 7 6 theme growth 1098:1103 arg1 protein-43 1116:1125 growth associated protein-43 1098:1125 growth associated protein-43 1098:1125 Immunohistochemistry demonstrated that mature and immature olfactory sensory neurons of OEs express the olfactory marker protein and growth associated protein-43, respectively. 36448434 2 7 theme olfactory 271:279 arg1 OE 293:294 OE 293:294 OE 293:294 The terminal carbohydrates of glycoconjugates influence chemoreception in the olfactory epithelium (OE). 36448434 2 7 theme olfactory 271:279 arg1 epithelium 281:290 the olfactory epithelium 267:290 the olfactory epithelium (OE) 267:295 The terminal carbohydrates of glycoconjugates influence chemoreception in the olfactory epithelium (OE). 36448434 8 8 theme numerous 1179:1186 arg1 glycoconjugates 1188:1202 numerous glycoconjugates 1179:1202 numerous glycoconjugates 1179:1202 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 4 9 theme histochemical 658:670 arg1 methods 672:678 histological, immunohistochemical, and lectin histochemical methods 612:678 histological, immunohistochemical, and lectin histochemical methods 612:678 METHODS The OM of neonate and adult Korean native cattle was evaluated using histological, immunohistochemical, and lectin histochemical methods. 36448434 1 10 theme odorant 144:150 arg1 perception 152:161 odorant perception 144:161 odorant perception in the main olfactory system 144:190 BACKGROUND The olfactory mucosa (OM) is crucial for odorant perception in the main olfactory system. 36448434 7 11 theme olfactory 1069:1077 arg1 protein 1086:1092 the olfactory marker protein 1065:1092 the olfactory marker protein 1065:1092 Immunohistochemistry demonstrated that mature and immature olfactory sensory neurons of OEs express the olfactory marker protein and growth associated protein-43, respectively. 36448434 4 12 theme immunohistochemical 626:644 arg1 methods 672:678 histological, immunohistochemical, and lectin histochemical methods 612:678 histological, immunohistochemical, and lectin histochemical methods 612:678 METHODS The OM of neonate and adult Korean native cattle was evaluated using histological, immunohistochemical, and lectin histochemical methods. 36448434 11 13 theme labeling 1870:1877 arg1 properties 1879:1888 their labeling properties 1864:1888 their labeling properties 1864:1888 The findings suggest that glycoconjugates may play a role in olfactory chemoreception, and that their labeling properties may be closely related to OM development and maturity. 36448434 1 14 theme main 170:173 arg1 system 185:190 the main olfactory system 166:190 the main olfactory system 166:190 BACKGROUND The olfactory mucosa (OM) is crucial for odorant perception in the main olfactory system. 36448434 6 15 theme acini 921:925 arg1 specificity 878:888 the mucus specificity 868:888 the mucus specificity of the Bowman's gland duct and acini in the lamina propria 868:947 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 2 16 theme terminal 197:204 arg1 carbohydrates 206:218 The terminal carbohydrates 193:218 The terminal carbohydrates of glycoconjugates 193:237 The terminal carbohydrates of glycoconjugates influence chemoreception in the olfactory epithelium (OE). 36448434 6 17 theme duct 912:915 arg1 specificity 878:888 the mucus specificity 868:888 the mucus specificity of the Bowman's gland duct and acini in the lamina propria 868:947 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 8 18 theme fucose 1309:1314 arg1 groups 1316:1321 fucose groups 1309:1321 fucose groups 1309:1321 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 7 19 theme sensory 1034:1040 arg1 neurons 1042:1048 mature and immature olfactory sensory neurons 1004:1048 mature and immature olfactory sensory neurons of OEs 1004:1055 Immunohistochemistry demonstrated that mature and immature olfactory sensory neurons of OEs express the olfactory marker protein and growth associated protein-43, respectively. 36448434 1 20 theme olfactory 107:115 arg1 mucosa 117:122 The olfactory mucosa 103:122 The olfactory mucosa (OM) 103:127 BACKGROUND The olfactory mucosa (OM) is crucial for odorant perception in the main olfactory system. 36448434 1 20 theme olfactory 107:115 arg1 OM 125:126 OM 125:126 OM 125:126 BACKGROUND The olfactory mucosa (OM) is crucial for odorant perception in the main olfactory system. 36448434 1 20 theme olfactory 107:115 arg1 crucial 132:138 crucial 132:138 crucial 132:138 BACKGROUND The olfactory mucosa (OM) is crucial for odorant perception in the main olfactory system. 36448434 7 21 theme immature 1015:1022 arg1 neurons 1042:1048 mature and immature olfactory sensory neurons 1004:1048 mature and immature olfactory sensory neurons of OEs 1004:1055 Immunohistochemistry demonstrated that mature and immature olfactory sensory neurons of OEs express the olfactory marker protein and growth associated protein-43, respectively. 36448434 1 22 from perception 152:161 arg1 system 185:190 the main olfactory system 166:190 the main olfactory system 166:190 BACKGROUND The olfactory mucosa (OM) is crucial for odorant perception in the main olfactory system. 36448434 9 23 theme olfactory 1506:1514 arg1 system 1516:1521 a well-developed olfactory system 1489:1521 a well-developed olfactory system 1489:1521 According to our observations, the cattle possessed a well-developed olfactory system, and the expression patterns of glycoconjugates in neonatal and adult OMs varied considerably. 36448434 3 24 theme histological 313:324 arg1 characteristics 326:340 The histological characteristics 309:340 The histological characteristics 309:340 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 0 25 theme native 56:61 arg1 cattle 63:68 Korean native cattle 49:68 Korean native cattle 49:68 Lectin histochemistry of the olfactory mucosa of Korean native cattle, Bos taurus coreanae. 36448434 8 26 theme varied 1342:1347 arg1 levels 1349:1354 varied levels 1342:1354 varied levels in the different cell types 1342:1382 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 10 27 theme lectin 1745:1750 arg1 histochemistry 1752:1765 lectin histochemistry 1745:1765 lectin histochemistry 1745:1765 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 8 28 theme different 1363:1371 arg1 types 1378:1382 the different cell types 1359:1382 the different cell types 1359:1382 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 9 29 theme glycoconjugates 1555:1569 arg1 patterns 1543:1550 the expression patterns 1528:1550 the expression patterns of glycoconjugates in neonatal and adult OMs 1528:1595 According to our observations, the cattle possessed a well-developed olfactory system, and the expression patterns of glycoconjugates in neonatal and adult OMs varied considerably. 36448434 0 30 theme Lectin 0:5 arg1 histochemistry 7:20 Lectin histochemistry 0:20 Lectin histochemistry of the olfactory mucosa of Korean native cattle 0:68 Lectin histochemistry of the olfactory mucosa of Korean native cattle, Bos taurus coreanae. 36448434 9 31 theme neonatal 1574:1581 arg1 OMs 1593:1595 neonatal and adult OMs 1574:1595 neonatal and adult OMs 1574:1595 According to our observations, the cattle possessed a well-developed olfactory system, and the expression patterns of glycoconjugates in neonatal and adult OMs varied considerably. 36448434 3 32 dep OBJECTIVES 298:307 arg1 characteristics 326:340 The histological characteristics 309:340 The histological characteristics 309:340 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 9 33 theme adult 1587:1591 arg1 OMs 1593:1595 neonatal and adult OMs 1574:1595 neonatal and adult OMs 1574:1595 According to our observations, the cattle possessed a well-developed olfactory system, and the expression patterns of glycoconjugates in neonatal and adult OMs varied considerably. 36448434 4 34 theme neonate 553:559 arg1 OM 547:548 The OM 543:548 METHODS The OM of neonate and adult Korean native cattle 535:590 METHODS The OM of neonate and adult Korean native cattle was evaluated using histological, immunohistochemical, and lectin histochemical methods. 36448434 11 35 theme OM 1916:1917 arg1 development 1919:1929 development 1919:1929 development 1919:1929 The findings suggest that glycoconjugates may play a role in olfactory chemoreception, and that their labeling properties may be closely related to OM development and maturity. 36448434 10 36 theme morphological 1670:1682 arg1 assessment 1684:1693 the morphological assessment 1666:1693 the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry 1666:1765 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 0 37 theme olfactory 29:37 arg1 mucosa 39:44 the olfactory mucosa 25:44 the olfactory mucosa of Korean native cattle 25:68 Lectin histochemistry of the olfactory mucosa of Korean native cattle, Bos taurus coreanae. 36448434 5 38 theme lamina 785:790 arg1 propria 792:798 the lamina propria 781:798 the lamina propria 781:798 RESULTS Histologically, the OM in both neonates and adults consists of the olfactory epithelium and the lamina propria. 36448434 3 39 dep Bos 416:418 arg1 coreae 427:432 Bos taurus coreae 416:432 Bos taurus coreae 416:432 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 3 40 theme native 393:398 arg1 cattle 400:405 Korean native cattle 386:405 Korean native cattle (Hanwoo, Bos taurus coreae) 386:433 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 5 41 theme olfactory 756:764 arg1 epithelium 766:775 the olfactory epithelium 752:775 the olfactory epithelium 752:775 RESULTS Histologically, the OM in both neonates and adults consists of the olfactory epithelium and the lamina propria. 36448434 10 42 theme Korean 1708:1713 arg1 cattle 1722:1727 Korean native cattle 1708:1727 Korean native cattle with a focus on lectin histochemistry 1708:1765 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 10 43 with cattle 1722:1727 arg1 focus 1736:1740 a focus 1734:1740 a focus on lectin histochemistry 1734:1765 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 10 44 theme OM 1702:1703 arg1 assessment 1684:1693 the morphological assessment 1666:1693 the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry 1666:1765 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 8 45 from levels 1349:1354 arg1 types 1378:1382 the different cell types 1359:1382 the different cell types 1359:1382 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 7 46 theme associated 1105:1114 arg1 protein-43 1116:1125 growth associated protein-43 1098:1125 growth associated protein-43 1098:1125 Immunohistochemistry demonstrated that mature and immature olfactory sensory neurons of OEs express the olfactory marker protein and growth associated protein-43, respectively. 36448434 3 47 theme possible 486:493 arg1 functions 495:503 possible functions 486:503 possible functions 486:503 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 4 48 theme adult 565:569 arg1 cattle 585:590 adult Korean native cattle 565:590 adult Korean native cattle 565:590 METHODS The OM of neonate and adult Korean native cattle was evaluated using histological, immunohistochemical, and lectin histochemical methods. 36448434 5 49 from OM 709:710 arg1 adults 733:738 adults 733:738 adults 733:738 RESULTS Histologically, the OM in both neonates and adults consists of the olfactory epithelium and the lamina propria. 36448434 5 49 from OM 709:710 arg1 neonates 720:727 neonates 720:727 neonates 720:727 RESULTS Histologically, the OM in both neonates and adults consists of the olfactory epithelium and the lamina propria. 36448434 6 50 theme mucus 872:876 arg1 specificity 878:888 the mucus specificity 868:888 the mucus specificity of the Bowman's gland duct and acini in the lamina propria 868:947 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 4 51 theme native 578:583 arg1 cattle 585:590 adult Korean native cattle 565:590 adult Korean native cattle 565:590 METHODS The OM of neonate and adult Korean native cattle was evaluated using histological, immunohistochemical, and lectin histochemical methods. 36448434 7 52 theme marker 1079:1084 arg1 protein 1086:1092 the olfactory marker protein 1065:1092 the olfactory marker protein 1065:1092 Immunohistochemistry demonstrated that mature and immature olfactory sensory neurons of OEs express the olfactory marker protein and growth associated protein-43, respectively. 36448434 6 53 from propria 941:947 arg1 specificity 878:888 the mucus specificity 868:888 the mucus specificity of the Bowman's gland duct and acini in the lamina propria 868:947 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 6 54 theme lamina 934:939 arg1 propria 941:947 the lamina propria 930:947 the lamina propria 930:947 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 7 55 theme OEs 1053:1055 arg1 neurons 1042:1048 mature and immature olfactory sensory neurons 1004:1048 mature and immature olfactory sensory neurons of OEs 1004:1055 Immunohistochemistry demonstrated that mature and immature olfactory sensory neurons of OEs express the olfactory marker protein and growth associated protein-43, respectively. 36448434 8 56 theme complex 1282:1288 arg1 N-glycan 1295:1302 complex type N-glycan 1282:1302 complex type N-glycan 1282:1302 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 1 57 theme olfactory 175:183 arg1 system 185:190 the main olfactory system 166:190 the main olfactory system 166:190 BACKGROUND The olfactory mucosa (OM) is crucial for odorant perception in the main olfactory system. 36448434 11 58 theme olfactory 1829:1837 arg1 chemoreception 1839:1852 olfactory chemoreception 1829:1852 olfactory chemoreception 1829:1852 The findings suggest that glycoconjugates may play a role in olfactory chemoreception, and that their labeling properties may be closely related to OM development and maturity. 36448434 7 59 theme olfactory 1024:1032 arg1 neurons 1042:1048 mature and immature olfactory sensory neurons 1004:1048 mature and immature olfactory sensory neurons of OEs 1004:1055 Immunohistochemistry demonstrated that mature and immature olfactory sensory neurons of OEs express the olfactory marker protein and growth associated protein-43, respectively. 36448434 7 60 theme mature 1004:1009 arg1 neurons 1042:1048 mature and immature olfactory sensory neurons 1004:1048 mature and immature olfactory sensory neurons of OEs 1004:1055 Immunohistochemistry demonstrated that mature and immature olfactory sensory neurons of OEs express the olfactory marker protein and growth associated protein-43, respectively. 36448434 6 61 theme gland 906:910 arg1 duct 912:915 the Bowman's gland duct 893:915 the Bowman's gland duct 893:915 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 9 62 theme well-developed 1491:1504 arg1 system 1516:1521 a well-developed olfactory system 1489:1521 a well-developed olfactory system 1489:1521 According to our observations, the cattle possessed a well-developed olfactory system, and the expression patterns of glycoconjugates in neonatal and adult OMs varied considerably. 36448434 10 63 from focus 1736:1740 arg1 histochemistry 1752:1765 lectin histochemistry 1745:1765 lectin histochemistry 1745:1765 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 0 64 theme cattle 63:68 arg1 mucosa 39:44 the olfactory mucosa 25:44 the olfactory mucosa of Korean native cattle 25:68 Lectin histochemistry of the olfactory mucosa of Korean native cattle, Bos taurus coreanae. 36448434 2 65 theme glycoconjugates 223:237 arg1 carbohydrates 206:218 The terminal carbohydrates 193:218 The terminal carbohydrates of glycoconjugates 193:237 The terminal carbohydrates of glycoconjugates influence chemoreception in the olfactory epithelium (OE). 36448434 8 66 theme type 1290:1293 arg1 N-glycan 1295:1302 complex type N-glycan 1282:1302 complex type N-glycan 1282:1302 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 1 67 dep BACKGROUND 92:101 arg1 mucosa 117:122 The olfactory mucosa 103:122 The olfactory mucosa (OM) 103:127 BACKGROUND The olfactory mucosa (OM) is crucial for odorant perception in the main olfactory system. 36448434 1 67 dep BACKGROUND 92:101 arg1 crucial 132:138 crucial 132:138 crucial 132:138 BACKGROUND The olfactory mucosa (OM) is crucial for odorant perception in the main olfactory system. 36448434 4 68 dep METHODS 535:541 arg1 OM 547:548 The OM 543:548 METHODS The OM of neonate and adult Korean native cattle 535:590 METHODS The OM of neonate and adult Korean native cattle was evaluated using histological, immunohistochemical, and lectin histochemical methods. 36448434 9 69 theme expression 1532:1541 arg1 patterns 1543:1550 the expression patterns 1528:1550 the expression patterns of glycoconjugates in neonatal and adult OMs 1528:1595 According to our observations, the cattle possessed a well-developed olfactory system, and the expression patterns of glycoconjugates in neonatal and adult OMs varied considerably. 36448434 9 70 from patterns 1543:1550 arg1 OMs 1593:1595 neonatal and adult OMs 1574:1595 neonatal and adult OMs 1574:1595 According to our observations, the cattle possessed a well-developed olfactory system, and the expression patterns of glycoconjugates in neonatal and adult OMs varied considerably. 36448434 3 71 theme glycoconjugate 346:359 arg1 composition 361:371 glycoconjugate composition 346:371 glycoconjugate composition 346:371 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 3 72 dep cattle 400:405 arg1 Bos 416:418 Bos 416:418 Bos 416:418 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 3 72 dep cattle 400:405 arg1 Hanwoo 408:413 Hanwoo 408:413 Hanwoo 408:413 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 0 73 dep Bos 71:73 arg1 coreanae 82:89 Bos taurus coreanae 71:89 Bos taurus coreanae 71:89 Lectin histochemistry of the olfactory mucosa of Korean native cattle, Bos taurus coreanae. 36448434 0 73 dep Bos 71:73 arg1 histochemistry 7:20 Lectin histochemistry 0:20 Lectin histochemistry of the olfactory mucosa of Korean native cattle 0:68 Lectin histochemistry of the olfactory mucosa of Korean native cattle, Bos taurus coreanae. 36448434 3 74 theme Korean 386:391 arg1 cattle 400:405 Korean native cattle 386:405 Korean native cattle (Hanwoo, Bos taurus coreae) 386:433 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 8 75 theme cell 1373:1376 arg1 types 1378:1382 the different cell types 1359:1382 the different cell types 1359:1382 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 10 76 theme first 1642:1646 arg1 This 1630:1633 This 1630:1633 This 1630:1633 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 10 76 theme first 1642:1646 arg1 study 1648:1652 the first study 1638:1652 the first study 1638:1652 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 3 77 theme OM 380:381 arg1 OBJECTIVES 298:307 OBJECTIVES 298:307 OBJECTIVES 298:307 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 3 77 theme OM 380:381 arg1 composition 361:371 glycoconjugate composition 346:371 glycoconjugate composition 346:371 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 6 78 from acini 921:925 arg1 propria 941:947 the lamina propria 930:947 the lamina propria 930:947 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 0 79 theme mucosa 39:44 arg1 histochemistry 7:20 Lectin histochemistry 0:20 Lectin histochemistry of the olfactory mucosa of Korean native cattle 0:68 Lectin histochemistry of the olfactory mucosa of Korean native cattle, Bos taurus coreanae. 36448434 9 80 contain possessed 1479:1487 arg2 system 1516:1521 a well-developed olfactory system 1489:1521 a well-developed olfactory system 1489:1521 According to our observations, the cattle possessed a well-developed olfactory system, and the expression patterns of glycoconjugates in neonatal and adult OMs varied considerably. 36448434 9 80 contain possessed 1479:1487 arg1 cattle 1472:1477 the cattle 1468:1477 the cattle 1468:1477 According to our observations, the cattle possessed a well-developed olfactory system, and the expression patterns of glycoconjugates in neonatal and adult OMs varied considerably. 36448434 0 81 theme Korean 49:54 arg1 cattle 63:68 Korean native cattle 49:68 Korean native cattle 49:68 Lectin histochemistry of the olfactory mucosa of Korean native cattle, Bos taurus coreanae. 36448434 3 82 theme cattle 400:405 arg1 OM 380:381 the OM 376:381 the OM of Korean native cattle (Hanwoo, Bos taurus coreae) 376:433 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 36448434 8 83 theme neonates 1398:1405 arg1 OMs 1391:1393 the OMs 1387:1393 the OMs of neonates and adults 1387:1416 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 6 84 from duct 912:915 arg1 propria 941:947 the lamina propria 930:947 the lamina propria 930:947 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 8 85 theme adults 1411:1416 arg1 OMs 1391:1393 the OMs 1387:1393 the OMs of neonates and adults 1387:1416 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 6 86 theme acid 830:833 arg1 pH 859:860 pH 2.5 859:864 pH 2.5 859:864 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 6 86 theme acid 830:833 arg1 Schiff 835:840 periodic acid Schiff 821:840 periodic acid Schiff 821:840 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 10 87 theme cattle 1722:1727 arg1 OM 1702:1703 the OM 1698:1703 the OM of Korean native cattle with a focus on lectin histochemistry 1698:1765 CONCLUSIONS This is the first study to describe the morphological assessment of the OM of Korean native cattle with a focus on lectin histochemistry. 36448434 4 88 theme histological 612:623 arg1 methods 672:678 histological, immunohistochemical, and lectin histochemical methods 612:678 histological, immunohistochemical, and lectin histochemical methods 612:678 METHODS The OM of neonate and adult Korean native cattle was evaluated using histological, immunohistochemical, and lectin histochemical methods. 36448434 6 89 from specificity 878:888 arg1 propria 941:947 the lamina propria 930:947 the lamina propria 930:947 Additionally, using periodic acid Schiff and Alcian blue (pH 2.5), the mucus specificity of the Bowman's gland duct and acini in the lamina propria was determined. 36448434 8 90 theme varying 1421:1427 arg1 levels 1429:1434 varying levels 1421:1434 varying levels 1421:1434 Lectin histochemistry indicated that numerous glycoconjugates, including as N-acetylglucosamine, mannose, galactose, N-acetylgalactosamine, complex type N-glycan, and fucose groups, were expressed at varied levels in the different cell types in the OMs of neonates and adults at varying levels. 36448434 3 91 theme postnatal 512:520 arg1 development 522:532 postnatal development 512:532 postnatal development 512:532 OBJECTIVES The histological characteristics and glycoconjugate composition of the OM of Korean native cattle (Hanwoo, Bos taurus coreae) were examined to characterize their morphology and possible functions during postnatal development. 37112626 0 0 theme Virus 87:91 arg1 NS1 93:95 Dengue Virus NS1 80:95 Dengue Virus NS1 80:95 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice. 37112626 5 1 gly glycosylation 831:843 arg2 site 845:848 an N-linked glycosylation site 819:848 an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability 819:906 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 5 2 theme glycosylation 831:843 arg1 site 845:848 an N-linked glycosylation site 819:848 an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability 819:906 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 1 3 theme public 223:228 arg1 threat 237:242 a major public health threat 215:242 a major public health threat 215:242 The four serotypes of dengue virus (DENV1-4) continue to pose a major public health threat. 37112626 0 4 theme Dengue 80:85 arg1 NS1 93:95 Dengue Virus NS1 80:95 Dengue Virus NS1 80:95 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice. 37112626 2 5 theme DENV1-4 320:326 arg1 proteins 308:315 the surface proteins 296:315 the surface proteins of DENV1-4 296:326 The first licenced dengue vaccine, which expresses the surface proteins of DENV1-4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. 37112626 8 6 theme CD4+ 1370:1373 arg1 responses 1382:1390 NS1-specific CD4+ T-cell responses 1357:1390 NS1-specific CD4+ T-cell responses 1357:1390 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 1 7 theme health 230:235 arg1 threat 237:242 a major public health threat 215:242 a major public health threat 215:242 The four serotypes of dengue virus (DENV1-4) continue to pose a major public health threat. 37112626 6 8 theme genetic 1043:1049 arg1 stability 1051:1059 high genetic stability 1038:1059 high genetic stability 1038:1059 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 9 9 theme pre-clinical 1542:1553 arg1 testing 1555:1561 further pre-clinical testing 1534:1561 further pre-clinical testing 1534:1561 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 2 10 theme dengue 264:269 arg1 vaccine 271:277 The first licenced dengue vaccine 245:277 The first licenced dengue vaccine 245:277 The first licenced dengue vaccine, which expresses the surface proteins of DENV1-4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. 37112626 4 11 theme vascular 705:712 arg1 leakage 714:720 vascular leakage 705:720 vascular leakage 705:720 However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. 37112626 0 12 theme NS1 93:95 arg1 Mutant 70:75 a Glycosylation Mutant 54:75 a Glycosylation Mutant of Dengue Virus NS1 54:95 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice. 37112626 5 13 theme virus 935:939 arg1 MVA 949:951 MVA 949:951 MVA 949:951 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 5 13 theme virus 935:939 arg1 Ankara 941:946 modified vaccinia virus Ankara 917:946 modified vaccinia virus Ankara (MVA) 917:952 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 5 13 theme virus 935:939 arg1 vector 959:964 a vector 957:964 a vector for its delivery 957:981 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 2 14 theme licenced 255:262 arg1 vaccine 271:277 The first licenced dengue vaccine 245:277 The first licenced dengue vaccine 245:277 The first licenced dengue vaccine, which expresses the surface proteins of DENV1-4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. 37112626 5 15 theme endothelial 878:888 arg1 hyperpermeability 890:906 NS1-induced endothelial hyperpermeability 866:906 NS1-induced endothelial hyperpermeability 866:906 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 9 16 theme vaccine 1503:1509 arg1 candidates 1511:1520 NS1-based vaccine candidates 1493:1520 NS1-based vaccine candidates 1493:1520 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 7 17 theme Secreted 1125:1132 arg1 NS1-N207Q 1134:1142 Secreted NS1-N207Q 1125:1142 Secreted NS1-N207Q 1125:1142 Secreted NS1-N207Q was composed of dimers and lacked N-linked glycosylation at position 207. 37112626 6 18 theme resulting 988:996 arg1 rMVA-D2-NS1-N207Q 1009:1025 rMVA-D2-NS1-N207Q 1009:1025 rMVA-D2-NS1-N207Q 1009:1025 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 6 18 theme resulting 988:996 arg1 construct 998:1006 The resulting construct 984:1006 The resulting construct 984:1006 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 2 19 theme first 249:253 arg1 vaccine 271:277 The first licenced dengue vaccine 245:277 The first licenced dengue vaccine 245:277 The first licenced dengue vaccine, which expresses the surface proteins of DENV1-4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. 37112626 5 20 theme NS1-induced 866:876 arg1 hyperpermeability 890:906 NS1-induced endothelial hyperpermeability 866:906 NS1-induced endothelial hyperpermeability 866:906 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 2 21 theme naïve 369:373 arg1 individuals 375:385 immunologically naïve individuals 353:385 immunologically naïve individuals 353:385 The first licenced dengue vaccine, which expresses the surface proteins of DENV1-4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. 37112626 0 22 theme Specific 105:112 arg1 Antibody 114:121 Specific Antibody 105:121 Specific Antibody 105:121 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice. 37112626 8 23 theme antibodies 1296:1305 arg1 levels 1273:1278 high levels 1268:1278 high levels of NS1-specific antibodies binding various conformations of NS1 1268:1342 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 6 24 theme efficient 1071:1079 arg1 secretion 1081:1089 drove efficient secretion 1065:1089 drove efficient secretion 1065:1089 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 0 25 theme Recombinant 0:10 arg1 Ankara 36:41 Recombinant Modified Vaccinia Virus Ankara 0:41 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 0:95 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice. 37112626 6 26 theme high 1038:1041 arg1 stability 1051:1059 high genetic stability 1038:1059 high genetic stability 1038:1059 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 5 27 used used 912:915 arg2 we 785:786 we 785:786 we 785:786 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 0 28 theme Modified 12:19 arg1 Ankara 36:41 Recombinant Modified Vaccinia Virus Ankara 0:41 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 0:95 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice. 37112626 7 29 theme N-linked 1178:1185 arg1 glycosylation 1187:1199 N-linked glycosylation 1178:1199 N-linked glycosylation 1178:1199 Secreted NS1-N207Q was composed of dimers and lacked N-linked glycosylation at position 207. 37112626 3 30 theme dengue 539:544 arg1 disease 546:552 severe dengue disease 532:552 severe dengue disease 532:552 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 1 31 theme dengue 175:180 arg1 DENV1-4 189:195 DENV1-4 189:195 DENV1-4 189:195 The four serotypes of dengue virus (DENV1-4) continue to pose a major public health threat. 37112626 1 31 theme dengue 175:180 arg1 virus 182:186 dengue virus 175:186 dengue virus (DENV1-4) 175:196 The four serotypes of dengue virus (DENV1-4) continue to pose a major public health threat. 37112626 2 32 theme dengue 426:431 arg1 disease 433:439 antibody-enhanced dengue disease 408:439 antibody-enhanced dengue disease 408:439 The first licenced dengue vaccine, which expresses the surface proteins of DENV1-4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. 37112626 9 33 theme infection 1597:1605 arg1 model 1583:1587 a relevant mouse model 1566:1587 a relevant mouse model of DENV infection 1566:1605 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 3 34 theme disease 546:552 arg1 leakage 507:513 vascular leakage 498:513 vascular leakage 498:513 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 3 34 theme disease 546:552 arg1 hallmark 520:527 the hallmark 516:527 the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies 516:597 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 1 35 theme virus 182:186 arg1 serotypes 162:170 The four serotypes 153:170 The four serotypes of dengue virus (DENV1-4) 153:196 The four serotypes of dengue virus (DENV1-4) continue to pose a major public health threat. 37112626 0 36 theme Virus 30:34 arg1 Ankara 36:41 Recombinant Modified Vaccinia Virus Ankara 0:41 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 0:95 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice. 37112626 0 37 theme T-Cell 127:132 arg1 Responses 134:142 T-Cell Responses 127:142 T-Cell Responses 127:142 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice. 37112626 9 38 theme promising 1437:1445 arg1 rMVA-D2-NS1-N207Q 1414:1430 rMVA-D2-NS1-N207Q 1414:1430 rMVA-D2-NS1-N207Q 1414:1430 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 9 38 theme promising 1437:1445 arg1 alternative 1469:1479 a promising and potentially safer alternative 1435:1479 a promising and potentially safer alternative to existing NS1-based vaccine candidates 1435:1520 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 8 39 theme T-cell 1375:1380 arg1 responses 1382:1390 NS1-specific CD4+ T-cell responses 1357:1390 NS1-specific CD4+ T-cell responses 1357:1390 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 3 40 theme non-structural 447:460 arg1 NS1 473:475 NS1 473:475 NS1 473:475 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 3 40 theme non-structural 447:460 arg1 protein 462:468 DENV non-structural protein 1 442:470 DENV non-structural protein 1 (NS1) 442:476 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 0 41 theme Vaccinia 21:28 arg1 Ankara 36:41 Recombinant Modified Vaccinia Virus Ankara 0:41 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 0:95 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice. 37112626 9 42 theme mouse 1577:1581 arg1 model 1583:1587 a relevant mouse model 1566:1587 a relevant mouse model of DENV infection 1566:1605 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 3 43 theme severe 532:537 arg1 disease 546:552 severe dengue disease 532:552 severe dengue disease 532:552 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 6 44 from cells 1118:1122 arg1 stability 1051:1059 high genetic stability 1038:1059 high genetic stability 1038:1059 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 6 44 from cells 1118:1122 arg1 NS1-N207Q 1094:1102 NS1-N207Q 1094:1102 NS1-N207Q from infected cells 1094:1122 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 6 44 from cells 1118:1122 arg1 secretion 1081:1089 drove efficient secretion 1065:1089 drove efficient secretion 1065:1089 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 6 45 theme infected 1109:1116 arg1 cells 1118:1122 infected cells 1109:1122 infected cells 1109:1122 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 8 46 theme NS1 1340:1342 arg1 conformations 1323:1335 various conformations 1315:1335 various conformations of NS1 1315:1342 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 4 47 theme intrinsic 669:677 arg1 ability 679:685 the intrinsic ability 665:685 the intrinsic ability of NS1 to trigger vascular leakage 665:720 However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. 37112626 4 47 theme intrinsic 669:677 arg1 drawback 737:744 a potential drawback 725:744 a potential drawback of its use as a vaccine antigen 725:776 However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. 37112626 6 48 from stability 1051:1059 arg1 cells 1118:1122 infected cells 1109:1122 infected cells 1109:1122 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 3 49 theme attractive 613:622 arg1 target 624:629 an attractive target 610:629 it an attractive target for vaccine development 607:653 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 4 50 theme vaccine 762:768 arg1 antigen 770:776 a vaccine antigen 760:776 a vaccine antigen 760:776 However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. 37112626 9 51 theme safer 1463:1467 arg1 rMVA-D2-NS1-N207Q 1414:1430 rMVA-D2-NS1-N207Q 1414:1430 rMVA-D2-NS1-N207Q 1414:1430 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 9 51 theme safer 1463:1467 arg1 alternative 1469:1479 a promising and potentially safer alternative 1435:1479 a promising and potentially safer alternative to existing NS1-based vaccine candidates 1435:1520 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 8 52 theme mice 1255:1258 arg1 immunisation 1230:1241 Prime-boost immunisation 1218:1241 Prime-boost immunisation of C57BL/6J mice 1218:1258 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 5 53 theme DENV2 797:801 arg1 NS1 803:805 DENV2 NS1 797:805 DENV2 NS1 797:805 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 5 54 link N-linked 822:829 arg1 site 845:848 an N-linked glycosylation site 819:848 an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability 819:906 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 8 55 theme NS1-specific 1283:1294 arg1 antibodies 1296:1305 NS1-specific antibodies 1283:1305 NS1-specific antibodies binding various conformations of NS1 1283:1342 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 2 56 theme antibody-enhanced 408:424 arg1 disease 433:439 antibody-enhanced dengue disease 408:439 antibody-enhanced dengue disease 408:439 The first licenced dengue vaccine, which expresses the surface proteins of DENV1-4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. 37112626 7 57 link N-linked 1178:1185 arg1 glycosylation 1187:1199 N-linked glycosylation 1178:1199 N-linked glycosylation 1178:1199 Secreted NS1-N207Q was composed of dimers and lacked N-linked glycosylation at position 207. 37112626 3 58 theme DENV 442:445 arg1 NS1 473:475 NS1 473:475 NS1 473:475 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 3 58 theme DENV 442:445 arg1 protein 462:468 DENV non-structural protein 1 442:470 DENV non-structural protein 1 (NS1) 442:476 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 0 59 theme Glycosylation 56:68 arg1 Mutant 70:75 a Glycosylation Mutant 54:75 a Glycosylation Mutant of Dengue Virus NS1 54:95 Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice. 37112626 8 60 theme NS1-specific 1357:1368 arg1 responses 1382:1390 NS1-specific CD4+ T-cell responses 1357:1390 NS1-specific CD4+ T-cell responses 1357:1390 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 8 61 theme high 1268:1271 arg1 levels 1273:1278 high levels 1268:1278 high levels of NS1-specific antibodies binding various conformations of NS1 1268:1342 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 3 62 theme vaccine 635:641 arg1 development 643:653 vaccine development 635:653 vaccine development 635:653 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 8 63 theme Prime-boost 1218:1228 arg1 immunisation 1230:1241 Prime-boost immunisation 1218:1241 Prime-boost immunisation of C57BL/6J mice 1218:1258 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 4 64 theme NS1 690:692 arg1 ability 679:685 the intrinsic ability 665:685 the intrinsic ability of NS1 to trigger vascular leakage 665:720 However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. 37112626 4 64 theme NS1 690:692 arg1 drawback 737:744 a potential drawback 725:744 a potential drawback of its use as a vaccine antigen 725:776 However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. 37112626 4 65 theme use 753:755 arg1 ability 679:685 the intrinsic ability 665:685 the intrinsic ability of NS1 to trigger vascular leakage 665:720 However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. 37112626 4 65 theme use 753:755 arg1 drawback 737:744 a potential drawback 725:744 a potential drawback of its use as a vaccine antigen 725:776 However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. 37112626 6 66 from secretion 1081:1089 arg1 cells 1118:1122 infected cells 1109:1122 infected cells 1109:1122 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 2 67 theme surface 300:306 arg1 proteins 308:315 the surface proteins 296:315 the surface proteins of DENV1-4 296:326 The first licenced dengue vaccine, which expresses the surface proteins of DENV1-4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. 37112626 6 68 theme drove 1065:1069 arg1 secretion 1081:1089 drove efficient secretion 1065:1089 drove efficient secretion 1065:1089 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 4 69 theme potential 727:735 arg1 ability 679:685 the intrinsic ability 665:685 the intrinsic ability of NS1 to trigger vascular leakage 665:720 However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. 37112626 4 69 theme potential 727:735 arg1 drawback 737:744 a potential drawback 725:744 a potential drawback of its use as a vaccine antigen 725:776 However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. 37112626 5 70 theme vaccinia 926:933 arg1 MVA 949:951 MVA 949:951 MVA 949:951 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 5 70 theme vaccinia 926:933 arg1 Ankara 941:946 modified vaccinia virus Ankara 917:946 modified vaccinia virus Ankara (MVA) 917:952 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 5 70 theme vaccinia 926:933 arg1 vector 959:964 a vector 957:964 a vector for its delivery 957:981 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 5 71 theme N-linked 822:829 arg1 site 845:848 an N-linked glycosylation site 819:848 an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability 819:906 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 8 72 theme various 1315:1321 arg1 conformations 1323:1335 various conformations 1315:1335 various conformations of NS1 1315:1342 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 3 73 dep it 607:608 arg1 target 624:629 an attractive target 610:629 it an attractive target for vaccine development 607:653 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 9 74 theme NS1-based 1493:1501 arg1 candidates 1511:1520 NS1-based vaccine candidates 1493:1520 NS1-based vaccine candidates 1493:1520 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 8 75 theme C57BL/6J 1246:1253 arg1 mice 1255:1258 C57BL/6J mice 1246:1258 C57BL/6J mice 1246:1258 Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. 37112626 9 76 theme further 1534:1540 arg1 testing 1555:1561 further pre-clinical testing 1534:1561 further pre-clinical testing 1534:1561 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 5 77 theme modified 917:924 arg1 MVA 949:951 MVA 949:951 MVA 949:951 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 5 77 theme modified 917:924 arg1 Ankara 941:946 modified vaccinia virus Ankara 917:946 modified vaccinia virus Ankara (MVA) 917:952 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 5 77 theme modified 917:924 arg1 vector 959:964 a vector 957:964 a vector for its delivery 957:981 Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. 37112626 9 78 theme DENV 1592:1595 arg1 infection 1597:1605 DENV infection 1592:1605 DENV infection 1592:1605 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 9 79 theme relevant 1568:1575 arg1 model 1583:1587 a relevant mouse model 1566:1587 a relevant mouse model of DENV infection 1566:1605 Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection. 37112626 7 80 gly glycosylation 1187:1199 arg1 position 1204:1211 position 207 1204:1215 position 207 1204:1215 Secreted NS1-N207Q was composed of dimers and lacked N-linked glycosylation at position 207. 37112626 6 81 theme NS1-N207Q 1094:1102 arg1 stability 1051:1059 high genetic stability 1038:1059 high genetic stability 1038:1059 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 6 81 theme NS1-N207Q 1094:1102 arg1 secretion 1081:1089 drove efficient secretion 1065:1089 drove efficient secretion 1065:1089 The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. 37112626 3 82 theme NS1-specific 575:586 arg1 antibodies 588:597 NS1-specific antibodies 575:597 NS1-specific antibodies 575:597 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 3 83 theme vascular 498:505 arg1 leakage 507:513 vascular leakage 498:513 vascular leakage 498:513 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 3 83 theme vascular 498:505 arg1 hallmark 520:527 the hallmark 516:527 the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies 516:597 DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. 37112626 1 84 theme major 217:221 arg1 threat 237:242 a major public health threat 215:242 a major public health threat 215:242 The four serotypes of dengue virus (DENV1-4) continue to pose a major public health threat. 36778302 0 0 theme motif-dependent 60:74 arg1 site 16:19 A novel binding site 0:19 A novel binding site on the cryptic intervening domain 0:53 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 0 0 theme motif-dependent 60:74 arg1 regulator 76:84 a motif-dependent regulator 58:84 a motif-dependent regulator of O-GlcNAc transferase 58:108 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 3 1 theme OGT 648:650 arg1 interactions 668:679 OGT protein-protein interactions 648:679 OGT protein-protein interactions 648:679 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 1 2 theme O-linked 159:166 arg1 moieties 203:210 O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 159:210 O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 159:210 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 3 3 theme protein-protein 652:666 arg1 interactions 668:679 OGT protein-protein interactions 648:679 OGT protein-protein interactions 648:679 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 4 4 theme peptide 867:873 arg1 motif 875:879 a novel peptide motif 859:879 a novel peptide motif 859:879 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 3 5 theme intervening 531:541 arg1 protein 579:585 a poorly understood protein 559:585 a poorly understood protein fold found only in metazoan OGTs 559:618 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 3 5 theme intervening 531:541 arg1 domain 543:548 the intervening domain 527:548 the intervening domain (Int-D) 527:556 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 3 5 theme intervening 531:541 arg1 regulator 635:643 a specific regulator 624:643 a specific regulator of OGT protein-protein interactions and substrate modification 624:706 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 3 5 theme intervening 531:541 arg1 Int-D 551:555 Int-D 551:555 Int-D 551:555 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 6 6 theme recognition 1149:1159 arg1 mode 1127:1130 a novel mode 1119:1130 a novel mode of OGT substrate recognition 1119:1159 These findings illustrate a novel mode of OGT substrate recognition and offer the first insights into the biological roles of this unique domain. 36778302 4 7 theme specific 918:925 arg1 O-GlcNAcylation 927:941 specific O-GlcNAcylation 918:941 specific O-GlcNAcylation 918:941 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 4 8 theme novel 861:865 arg1 motif 875:879 a novel peptide motif 859:879 a novel peptide motif 859:879 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 4 9 theme phage 751:755 arg1 display 757:763 an innovative proteomic peptide phage display 719:763 an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations 719:842 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 4 9 theme phage 751:755 arg1 ProP-PD 766:772 ProP-PD 766:772 ProP-PD 766:772 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 0 10 theme transferase 98:108 arg1 site 16:19 A novel binding site 0:19 A novel binding site on the cryptic intervening domain 0:53 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 0 10 theme transferase 98:108 arg1 regulator 76:84 a motif-dependent regulator 58:84 a motif-dependent regulator of O-GlcNAc transferase 58:108 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 1 11 with modification 115:126 arg1 moieties 203:210 O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 159:210 O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 159:210 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 2 12 dep recognition 375:385 arg1 the 361:363 the 361:363 the 361:363 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 1 13 theme -acetylglucosamine 173:190 arg1 moieties 203:210 O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 159:210 O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 159:210 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 1 14 theme β- 168:169 arg1 -acetylglucosamine 173:190 β- N -acetylglucosamine 168:190 O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 159:210 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 1 14 theme β- 168:169 arg1 O-GlcNAc 193:200 O-GlcNAc 193:200 O-GlcNAc 193:200 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 0 15 theme O-GlcNAc 89:96 arg1 transferase 98:108 O-GlcNAc transferase 89:108 O-GlcNAc transferase 89:108 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 3 16 theme substrate 685:693 arg1 modification 695:706 substrate modification 685:706 substrate modification 685:706 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 4 17 theme cellular 817:824 arg1 characterizations 826:842 structural, biochemical, and cellular characterizations 788:842 structural, biochemical, and cellular characterizations 788:842 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 2 18 theme primary 443:449 arg1 transferase 420:430 O-GlcNAc transferase 411:430 O-GlcNAc transferase (OGT) 411:436 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 2 18 theme primary 443:449 arg1 enzyme 451:456 the primary enzyme 439:456 the primary enzyme responsible for O-GlcNAc addition 439:490 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 1 19 theme N 171:171 arg1 -acetylglucosamine 173:190 β- N -acetylglucosamine 168:190 O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 159:210 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 1 19 theme N 171:171 arg1 O-GlcNAc 193:200 O-GlcNAc 193:200 O-GlcNAc 193:200 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 0 20 theme novel 2:6 arg1 site 16:19 A novel binding site 0:19 A novel binding site on the cryptic intervening domain 0:53 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 0 20 theme novel 2:6 arg1 regulator 76:84 a motif-dependent regulator 58:84 a motif-dependent regulator of O-GlcNAc transferase 58:108 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 3 21 theme modification 695:706 arg1 domain 543:548 the intervening domain 527:548 the intervening domain (Int-D) 527:556 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 3 21 theme modification 695:706 arg1 regulator 635:643 a specific regulator 624:643 a specific regulator of OGT protein-protein interactions and substrate modification 624:706 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 5 22 theme binding 985:991 arg1 disruption 965:974 disruption 965:974 disruption of Int-D binding 965:991 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 4 23 theme innovative 722:731 arg1 display 757:763 an innovative proteomic peptide phage display 719:763 an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations 719:842 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 4 23 theme innovative 722:731 arg1 ProP-PD 766:772 ProP-PD 766:772 ProP-PD 766:772 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 2 24 theme regulation 391:400 arg1 modes 402:406 regulation modes 391:406 regulation modes 391:406 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 5 25 theme important 1006:1014 arg1 response 1060:1067 nutrient stress response 1044:1067 nutrient stress response 1044:1067 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 5 25 theme important 1006:1014 arg1 metabolism 1081:1090 glucose metabolism 1073:1090 glucose metabolism 1073:1090 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 5 25 theme important 1006:1014 arg1 programs 1025:1032 important cellular programs 1006:1032 important cellular programs including nutrient stress response and glucose metabolism 1006:1090 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 1 26 theme important 285:293 arg1 program 304:310 nearly every important cellular program 272:310 nearly every important cellular program 272:310 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 4 27 theme peptide 743:749 arg1 display 757:763 an innovative proteomic peptide phage display 719:763 an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations 719:842 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 4 27 theme peptide 743:749 arg1 ProP-PD 766:772 ProP-PD 766:772 ProP-PD 766:772 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 4 28 theme biochemical 800:810 arg1 characterizations 826:842 structural, biochemical, and cellular characterizations 788:842 structural, biochemical, and cellular characterizations 788:842 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 0 29 theme binding 8:14 arg1 site 16:19 A novel binding site 0:19 A novel binding site on the cryptic intervening domain 0:53 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 0 29 theme binding 8:14 arg1 regulator 76:84 a motif-dependent regulator 58:84 a motif-dependent regulator of O-GlcNAc transferase 58:108 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 1 30 theme cellular 295:302 arg1 program 304:310 nearly every important cellular program 272:310 nearly every important cellular program 272:310 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 1 31 link O-linked 159:166 arg1 moieties 203:210 O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 159:210 O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 159:210 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 5 32 theme glucose 1073:1079 arg1 metabolism 1081:1090 glucose metabolism 1073:1090 glucose metabolism 1073:1090 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 4 33 theme proteomic 733:741 arg1 display 757:763 an innovative proteomic peptide phage display 719:763 an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations 719:842 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 4 33 theme proteomic 733:741 arg1 ProP-PD 766:772 ProP-PD 766:772 ProP-PD 766:772 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 6 34 theme novel 1121:1125 arg1 mode 1127:1130 a novel mode 1119:1130 a novel mode of OGT substrate recognition 1119:1159 These findings illustrate a novel mode of OGT substrate recognition and offer the first insights into the biological roles of this unique domain. 36778302 2 35 theme O-GlcNAc 474:481 arg1 addition 483:490 O-GlcNAc addition 474:490 O-GlcNAc addition 474:490 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 3 36 theme understood 568:577 arg1 domain 543:548 the intervening domain 527:548 the intervening domain (Int-D) 527:556 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 3 36 theme understood 568:577 arg1 protein 579:585 a poorly understood protein 559:585 a poorly understood protein fold found only in metazoan OGTs 559:618 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 2 37 theme transferase 420:430 arg1 modes 402:406 regulation modes 391:406 regulation modes 391:406 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 2 37 theme transferase 420:430 arg1 recognition 375:385 substrate recognition 365:385 substrate recognition 365:385 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 3 38 theme metazoan 606:613 arg1 OGTs 615:618 metazoan OGTs 606:618 metazoan OGTs 606:618 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 5 39 theme cellular 1016:1023 arg1 response 1060:1067 nutrient stress response 1044:1067 nutrient stress response 1044:1067 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 5 39 theme cellular 1016:1023 arg1 metabolism 1081:1090 glucose metabolism 1073:1090 glucose metabolism 1073:1090 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 5 39 theme cellular 1016:1023 arg1 programs 1025:1032 important cellular programs 1006:1032 important cellular programs including nutrient stress response and glucose metabolism 1006:1090 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 2 40 theme O-GlcNAc 411:418 arg1 transferase 420:430 O-GlcNAc transferase 411:430 O-GlcNAc transferase (OGT) 411:436 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 2 40 theme O-GlcNAc 411:418 arg1 enzyme 451:456 the primary enzyme 439:456 the primary enzyme responsible for O-GlcNAc addition 439:490 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 2 40 theme O-GlcNAc 411:418 arg1 OGT 433:435 OGT 433:435 OGT 433:435 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 0 41 theme intervening 36:46 arg1 domain 48:53 the cryptic intervening domain 24:53 the cryptic intervening domain 24:53 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 6 42 theme domain 1231:1236 arg1 roles 1210:1214 the biological roles 1195:1214 the biological roles of this unique domain 1195:1236 These findings illustrate a novel mode of OGT substrate recognition and offer the first insights into the biological roles of this unique domain. 36778302 6 43 theme substrate 1139:1147 arg1 recognition 1149:1159 OGT substrate recognition 1135:1159 OGT substrate recognition 1135:1159 These findings illustrate a novel mode of OGT substrate recognition and offer the first insights into the biological roles of this unique domain. 36778302 0 44 theme cryptic 28:34 arg1 domain 48:53 the cryptic intervening domain 24:53 the cryptic intervening domain 24:53 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 3 45 theme interactions 668:679 arg1 domain 543:548 the intervening domain 527:548 the intervening domain (Int-D) 527:556 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 3 45 theme interactions 668:679 arg1 regulator 635:643 a specific regulator 624:643 a specific regulator of OGT protein-protein interactions and substrate modification 624:706 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 5 46 theme nutrient 1044:1051 arg1 response 1060:1067 nutrient stress response 1044:1067 nutrient stress response 1044:1067 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 6 47 theme unique 1224:1229 arg1 domain 1231:1236 this unique domain 1219:1236 this unique domain 1219:1236 These findings illustrate a novel mode of OGT substrate recognition and offer the first insights into the biological roles of this unique domain. 36778302 6 48 theme OGT 1135:1137 arg1 recognition 1149:1159 OGT substrate recognition 1135:1159 OGT substrate recognition 1135:1159 These findings illustrate a novel mode of OGT substrate recognition and offer the first insights into the biological roles of this unique domain. 36778302 5 49 theme stress 1053:1058 arg1 response 1060:1067 nutrient stress response 1044:1067 nutrient stress response 1044:1067 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 6 50 theme first 1175:1179 arg1 insights 1181:1188 the first insights 1171:1188 the first insights into the biological roles of this unique domain 1171:1236 These findings illustrate a novel mode of OGT substrate recognition and offer the first insights into the biological roles of this unique domain. 36778302 5 51 theme Int-D 979:983 arg1 binding 985:991 Int-D binding 979:991 Int-D binding 979:991 We further show that disruption of Int-D binding dysregulates important cellular programs including nutrient stress response and glucose metabolism. 36778302 1 52 theme proteins 145:152 arg1 modification 115:126 The modification 111:126 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 111:210 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 1 52 theme proteins 145:152 arg1 process 232:238 a highly dynamic process 215:238 a highly dynamic process that spatiotemporally regulates nearly every important cellular program 215:310 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 3 53 located found 592:596 arg2 domain 543:548 the intervening domain 527:548 the intervening domain (Int-D) 527:556 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 3 53 located found 592:596 arg2 protein 579:585 a poorly understood protein 559:585 a poorly understood protein fold found only in metazoan OGTs 559:618 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 3 53 located found 592:596 arg1 OGTs 615:618 metazoan OGTs 606:618 metazoan OGTs 606:618 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 3 54 theme specific 626:633 arg1 domain 543:548 the intervening domain 527:548 the intervening domain (Int-D) 527:556 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 3 54 theme specific 626:633 arg1 regulator 635:643 a specific regulator 624:643 a specific regulator of OGT protein-protein interactions and substrate modification 624:706 In this study, we have identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. 36778302 4 55 theme structural 788:797 arg1 characterizations 826:842 structural, biochemical, and cellular characterizations 788:842 structural, biochemical, and cellular characterizations 788:842 Utilizing an innovative proteomic peptide phage display (ProP-PD) coupled with structural, biochemical, and cellular characterizations, we discovered a novel peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. 36778302 1 56 theme intracellular 131:143 arg1 proteins 145:152 intracellular proteins 131:152 intracellular proteins 131:152 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 1 57 theme dynamic 224:230 arg1 modification 115:126 The modification 111:126 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties 111:210 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 1 57 theme dynamic 224:230 arg1 process 232:238 a highly dynamic process 215:238 a highly dynamic process that spatiotemporally regulates nearly every important cellular program 215:310 The modification of intracellular proteins with O-linked β- N -acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. 36778302 2 58 theme responsible 458:468 arg1 transferase 420:430 O-GlcNAc transferase 411:430 O-GlcNAc transferase (OGT) 411:436 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 2 58 theme responsible 458:468 arg1 enzyme 451:456 the primary enzyme 439:456 the primary enzyme responsible for O-GlcNAc addition 439:490 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 36778302 0 59 from site 16:19 arg1 domain 48:53 the cryptic intervening domain 24:53 the cryptic intervening domain 24:53 A novel binding site on the cryptic intervening domain is a motif-dependent regulator of O-GlcNAc transferase. 36778302 6 60 theme biological 1199:1208 arg1 roles 1210:1214 the biological roles 1195:1214 the biological roles of this unique domain 1195:1236 These findings illustrate a novel mode of OGT substrate recognition and offer the first insights into the biological roles of this unique domain. 36778302 2 61 theme substrate 365:373 arg1 recognition 375:385 substrate recognition 365:385 substrate recognition 365:385 Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. 37064333 0 0 theme Homozygous 69:78 arg1 Variant 93:99 Homozygous COG5 c.95T>G Variant 69:99 Homozygous COG5 c.95T>G Variant 69:99 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 37064333 2 1 theme fetal 622:626 arg1 length 636:641 short fetal humerus length 616:641 short fetal humerus length 616:641 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 1 theme fetal 622:626 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 5 2 theme c.95T>G 905:911 arg1 variant 913:919 homozygous COG5 c.95T>G variant 889:919 homozygous COG5 c.95T>G variant 889:919 We demonstrate the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant. 37064333 1 3 theme oligosaccharides 264:279 arg1 glycosylation 238:250 abnormal glycosylation 229:250 abnormal glycosylation of N-linked oligosaccharides 229:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 3 4 theme COG5 699:702 arg1 gene 704:707 the COG5 gene 695:707 the COG5 gene 695:707 Whole-exome sequencing was performed; the COG5 gene has shown a pathogenic variant. 37064333 2 5 theme short 616:620 arg1 length 636:641 short fetal humerus length 616:641 short fetal humerus length 616:641 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 5 theme short 616:620 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 1 6 gly glycosylation 238:250 arg1 oligosaccharides 264:279 N-linked oligosaccharides 255:279 N-linked oligosaccharides 255:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 0 7 theme c.95T>G 85:91 arg1 Variant 93:99 Homozygous COG5 c.95T>G Variant 69:99 Homozygous COG5 c.95T>G Variant 69:99 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 37064333 0 8 theme COG5 80:83 arg1 Variant 93:99 Homozygous COG5 c.95T>G Variant 69:99 Homozygous COG5 c.95T>G Variant 69:99 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 37064333 2 9 dep testing 327:333 arg1 week 341:344 24th week 336:344 24th week of pregnancy 336:357 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 10 theme abnormal 413:420 arg1 features/shape 429:442 abnormal facial features/shape 413:442 abnormal facial features/shape 413:442 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 10 theme abnormal 413:420 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 11 theme column 499:504 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 11 theme column 499:504 arg1 abnormality 506:516 vertebral column abnormality 489:516 vertebral column abnormality 489:516 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 1 12 theme autosomal 163:171 arg1 disorders 126:134 Introduction Congenital disorders 102:134 Introduction Congenital disorders of glycosylation (CDG) 102:157 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 1 12 theme autosomal 163:171 arg1 disorders 202:210 autosomal recessive hereditary genetic disorders 163:210 autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides 163:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 0 13 theme First 4:8 arg1 Disorders 21:29 The First Congenital Disorders 0:29 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 0:100 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 37064333 3 14 theme pathogenic 721:730 arg1 variant 732:738 a pathogenic variant 719:738 a pathogenic variant 719:738 Whole-exome sequencing was performed; the COG5 gene has shown a pathogenic variant. 37064333 1 15 link N-linked 255:262 arg1 oligosaccharides 264:279 N-linked oligosaccharides 255:279 N-linked oligosaccharides 255:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 4 16 theme Homozygous 752:761 arg1 patients 763:770 Discussion Homozygous patients 741:770 Discussion Homozygous patients 741:770 Discussion Homozygous patients have never been seen before in the literature for COG5-CDG. 37064333 1 17 theme recessive 173:181 arg1 disorders 126:134 Introduction Congenital disorders 102:134 Introduction Congenital disorders of glycosylation (CDG) 102:157 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 1 17 theme recessive 173:181 arg1 disorders 202:210 autosomal recessive hereditary genetic disorders 163:210 autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides 163:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 2 18 theme humerus 628:634 arg1 length 636:641 short fetal humerus length 616:641 short fetal humerus length 616:641 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 18 theme humerus 628:634 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 4 19 theme Discussion 741:750 arg1 patients 763:770 Discussion Homozygous patients 741:770 Discussion Homozygous patients 741:770 Discussion Homozygous patients have never been seen before in the literature for COG5-CDG. 37064333 1 20 theme hereditary 183:192 arg1 disorders 126:134 Introduction Congenital disorders 102:134 Introduction Congenital disorders of glycosylation (CDG) 102:157 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 1 20 theme hereditary 183:192 arg1 disorders 202:210 autosomal recessive hereditary genetic disorders 163:210 autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides 163:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 1 21 theme genetic 194:200 arg1 disorders 126:134 Introduction Congenital disorders 102:134 Introduction Congenital disorders of glycosylation (CDG) 102:157 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 1 21 theme genetic 194:200 arg1 disorders 202:210 autosomal recessive hereditary genetic disorders 163:210 autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides 163:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 0 22 theme Congenital 10:19 arg1 Disorders 21:29 The First Congenital Disorders 0:29 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 0:100 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 37064333 5 23 with patient 861:867 arg1 variant 913:919 homozygous COG5 c.95T>G variant 889:919 homozygous COG5 c.95T>G variant 889:919 We demonstrate the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant. 37064333 3 24 theme Whole-exome 657:667 arg1 sequencing 669:678 Whole-exome sequencing 657:678 Whole-exome sequencing 657:678 Whole-exome sequencing was performed; the COG5 gene has shown a pathogenic variant. 37064333 2 25 theme prenatal 318:325 arg1 testing 327:333 prenatal testing 318:333 prenatal testing (24th week of pregnancy) 318:358 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 5 26 theme first 851:855 arg1 patient 861:867 the first CDG patient 847:867 the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant 847:919 We demonstrate the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant. 37064333 0 27 theme Glycosylation 34:46 arg1 Fetus 57:61 Fetus 57:61 Fetus 57:61 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 37064333 0 27 theme Glycosylation 34:46 arg1 Patient 48:54 Glycosylation Patient 34:54 Glycosylation Patient (Fetus) 34:62 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 37064333 2 28 theme pregnancy 349:357 arg1 week 341:344 24th week 336:344 24th week of pregnancy 336:357 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 29 theme kidney 567:572 arg1 morphology 574:583 abnormal kidney morphology 558:583 abnormal kidney morphology 558:583 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 29 theme kidney 567:572 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 5 30 theme CDG 857:859 arg1 patient 861:867 the first CDG patient 847:867 the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant 847:919 We demonstrate the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant. 37064333 2 31 theme vertebral 489:497 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 31 theme vertebral 489:497 arg1 abnormality 506:516 vertebral column abnormality 489:516 vertebral column abnormality 489:516 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 32 theme abnormal 558:565 arg1 morphology 574:583 abnormal kidney morphology 558:583 abnormal kidney morphology 558:583 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 32 theme abnormal 558:565 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 0 33 with Disorders 21:29 arg1 Variant 93:99 Homozygous COG5 c.95T>G Variant 69:99 Homozygous COG5 c.95T>G Variant 69:99 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 37064333 2 34 theme facial 422:427 arg1 features/shape 429:442 abnormal facial features/shape 413:442 abnormal facial features/shape 413:442 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 34 theme facial 422:427 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 5 35 theme homozygous 889:898 arg1 variant 913:919 homozygous COG5 c.95T>G variant 889:919 homozygous COG5 c.95T>G variant 889:919 We demonstrate the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant. 37064333 1 36 theme Introduction 102:113 arg1 disorders 126:134 Introduction Congenital disorders 102:134 Introduction Congenital disorders of glycosylation (CDG) 102:157 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 1 36 theme Introduction 102:113 arg1 disorders 202:210 autosomal recessive hereditary genetic disorders 163:210 autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides 163:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 0 37 theme Patient 48:54 arg1 Disorders 21:29 The First Congenital Disorders 0:29 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 0:100 The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant. 37064333 2 38 theme femur 598:602 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 38 theme femur 598:602 arg1 length 604:609 short fetal femur length 586:609 short fetal femur length 586:609 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 1 39 theme Congenital 115:124 arg1 disorders 126:134 Introduction Congenital disorders 102:134 Introduction Congenital disorders of glycosylation (CDG) 102:157 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 1 39 theme Congenital 115:124 arg1 disorders 202:210 autosomal recessive hereditary genetic disorders 163:210 autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides 163:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 2 40 theme fetal 592:596 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 40 theme fetal 592:596 arg1 length 604:609 short fetal femur length 586:609 short fetal femur length 586:609 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 1 41 theme abnormal 229:236 arg1 glycosylation 238:250 abnormal glycosylation 229:250 abnormal glycosylation of N-linked oligosaccharides 229:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 2 42 theme short 586:590 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 42 theme short 586:590 arg1 length 604:609 short fetal femur length 586:609 short fetal femur length 586:609 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 43 theme Case 282:285 arg1 Presentation 287:298 Case Presentation 282:298 Case Presentation 282:298 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 5 44 from stage 878:882 arg1 patient 861:867 the first CDG patient 847:867 the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant 847:919 We demonstrate the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant. 37064333 5 45 theme COG5 900:903 arg1 variant 913:919 homozygous COG5 c.95T>G variant 889:919 homozygous COG5 c.95T>G variant 889:919 We demonstrate the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant. 37064333 2 46 theme brain 445:449 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 46 theme brain 445:449 arg1 abnormality 462:472 brain morphology abnormality 445:472 brain morphology abnormality 445:472 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 1 47 theme glycosylation 139:151 arg1 disorders 126:134 Introduction Congenital disorders 102:134 Introduction Congenital disorders of glycosylation (CDG) 102:157 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 1 47 theme glycosylation 139:151 arg1 disorders 202:210 autosomal recessive hereditary genetic disorders 163:210 autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides 163:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 37064333 5 48 theme fetus 872:876 arg1 stage 878:882 fetus stage 872:882 fetus stage 872:882 We demonstrate the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant. 37064333 2 49 theme morphology 451:460 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 49 theme morphology 451:460 arg1 abnormality 462:472 brain morphology abnormality 445:472 brain morphology abnormality 445:472 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 50 theme spina 475:479 arg1 findings 369:376 findings 369:376 findings like polyhydramnios 369:396 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 2 50 theme spina 475:479 arg1 bifida 481:486 spina bifida 475:486 spina bifida 475:486 Case Presentation In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. 37064333 1 51 theme N-linked 255:262 arg1 oligosaccharides 264:279 N-linked oligosaccharides 255:279 N-linked oligosaccharides 255:279 Introduction Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. 35147430 6 0 contain contain 1046:1052 arg1 that 1041:1044 that 1041:1044 that 1041:1044 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 6 0 contain contain 1046:1052 arg1 orientation 1113:1123 the anti and/or syn glycosidic orientation 1082:1123 orientation 1113:1123 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 6 0 contain contain 1046:1052 arg2 that 1041:1044 that 1041:1044 that 1041:1044 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 6 0 contain contain 1046:1052 arg2 adducts 1071:1077 one or two ABPdG adducts 1054:1077 one or two ABPdG adducts 1054:1077 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 6 0 contain contain 1046:1052 arg1 s 1125:1125 s 1125:1125 s 1125:1125 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 6 0 contain contain 1046:1052 arg1 anti 1086:1089 anti 1086:1089 anti 1086:1089 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 0 1 theme DNA 140:142 arg1 Structure 144:152 a Damaged DNA Structure 130:152 a Damaged DNA Structure 130:152 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 8 2 theme next-nearest 1710:1721 arg1 sites 1740:1744 next-nearest neighbor damaged sites 1710:1744 next-nearest neighbor damaged sites (G2G3) 1710:1751 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 8 2 theme next-nearest 1710:1721 arg1 G2G3 1747:1750 G2G3 1747:1750 G2G3 1747:1750 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 8 3 theme lesion 1547:1552 arg1 effects 1565:1571 interesting lesion separation effects 1535:1571 interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA 1535:1780 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 6 4 from combinations 1135:1146 arg1 anti 1086:1089 anti 1086:1089 anti 1086:1089 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 6 4 from combinations 1135:1146 arg1 hotspot 1190:1196 the NarI mutation hotspot 1172:1196 the NarI mutation hotspot for AAs (5'-G1G2CG3CC) 1172:1219 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 6 4 from combinations 1135:1146 arg1 s 1125:1125 s 1125:1125 s 1125:1125 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 3 5 contain containing 353:362 arg1 DNA 349:351 DNA 349:351 DNA containing a single AA-derived adduct (monoadducted DNA) 349:408 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 3 5 contain containing 353:362 arg2 DNA 405:407 monoadducted DNA 392:407 monoadducted DNA 392:407 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 3 5 contain containing 353:362 arg2 adduct 384:389 a single AA-derived adduct 364:389 a single AA-derived adduct (monoadducted DNA) 364:408 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 4 6 theme bulky 619:623 arg1 adducts 625:631 two bulky adducts 615:631 two bulky adducts (diadducted DNA) 615:648 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 4 6 theme bulky 619:623 arg1 DNA 645:647 diadducted DNA 634:647 diadducted DNA 634:647 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 8 7 theme damaged 1732:1738 arg1 sites 1740:1744 next-nearest neighbor damaged sites 1710:1744 next-nearest neighbor damaged sites (G2G3) 1710:1751 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 8 7 theme damaged 1732:1738 arg1 G2G3 1747:1750 G2G3 1747:1750 G2G3 1747:1750 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 6 8 theme positions 1159:1167 arg1 combinations 1135:1146 all combinations 1131:1146 all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC) 1131:1219 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 7 9 theme W 1490:1490 arg1 conformations 1493:1505 wedge (W) conformations] 1483:1506 wedge (W) conformations] 1483:1506 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 5 10 theme ABPdG 972:976 arg1 adduct 978:983 the widely studied N-linked ABPdG adduct 944:983 the widely studied N-linked ABPdG adduct 944:983 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 1 11 theme humans 167:172 arg1 Exposure 155:162 Exposure 155:162 Exposure of humans to carcinogenic aromatic amines (AAs) 155:210 Exposure of humans to carcinogenic aromatic amines (AAs) occurs daily. 35147430 7 12 theme wedge 1483:1487 arg1 conformations 1493:1505 wedge (W) conformations] 1483:1506 wedge (W) conformations] 1483:1506 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 7 13 theme conformational 1267:1280 arg1 heterogeneity 1282:1294 sequence-dependent conformational heterogeneity 1248:1294 sequence-dependent conformational heterogeneity 1248:1294 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 0 14 theme Molecular 102:110 arg1 Study 121:125 A Molecular Dynamics Study 100:125 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 0:153 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 5 15 theme μs 752:753 arg1 simulations 758:768 quintuplet 0.5 μs MD simulations 737:768 quintuplet 0.5 μs MD simulations 737:768 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 1 16 theme carcinogenic 177:188 arg1 AAs 207:209 AAs 207:209 AAs 207:209 Exposure of humans to carcinogenic aromatic amines (AAs) occurs daily. 35147430 1 16 theme carcinogenic 177:188 arg1 amines 199:204 carcinogenic aromatic amines 177:204 carcinogenic aromatic amines (AAs) 177:210 Exposure of humans to carcinogenic aromatic amines (AAs) occurs daily. 35147430 0 17 theme Damaged 132:138 arg1 Structure 144:152 a Damaged DNA Structure 130:152 a Damaged DNA Structure 130:152 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 9 18 theme elevated 2033:2040 arg1 levels 2042:2047 elevated levels 2033:2047 elevated levels of ABP 2033:2054 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 6 19 theme mutation 1181:1188 arg1 hotspot 1190:1196 the NarI mutation hotspot 1172:1196 the NarI mutation hotspot for AAs (5'-G1G2CG3CC) 1172:1219 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 8 20 theme greater 1622:1628 arg1 preference 1635:1644 a greater anti preference 1620:1644 a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA 1620:1780 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 8 21 theme neighbor 1723:1730 arg1 sites 1740:1744 next-nearest neighbor damaged sites 1710:1744 next-nearest neighbor damaged sites (G2G3) 1710:1751 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 8 21 theme neighbor 1723:1730 arg1 G2G3 1747:1750 G2G3 1747:1750 G2G3 1747:1750 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 7 22 theme Monoadducted 1222:1233 arg1 DNA 1235:1237 Monoadducted DNA 1222:1237 Monoadducted DNA 1222:1237 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 6 23 theme glycosidic 1102:1111 arg1 orientation 1113:1123 the anti and/or syn glycosidic orientation 1082:1123 orientation 1113:1123 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 4 24 dep conformation 560:571 arg1 the 556:558 the 556:558 the 556:558 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 8 25 theme neighboring 1650:1660 arg1 G1G2 1671:1674 G1G2 1671:1674 G1G2 1671:1674 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 8 25 theme neighboring 1650:1660 arg1 adducts 1662:1668 neighboring adducts 1650:1668 neighboring adducts (G1G2) 1650:1675 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 6 26 from anti 1086:1089 arg1 combinations 1135:1146 all combinations 1131:1146 all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC) 1131:1219 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 5 27 theme studied 955:961 arg1 adduct 978:983 the widely studied N-linked ABPdG adduct 944:983 the widely studied N-linked ABPdG adduct 944:983 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 5 28 theme potent 829:834 arg1 carcinogen 844:853 the potent bladder carcinogen 4-aminobiphenyl (ABP) 825:875 the potent bladder carcinogen 4-aminobiphenyl (ABP) 825:875 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 0 29 from Effects 0:6 arg1 Toxicity 50:57 the Toxicity 46:57 the Toxicity of the Human Carcinogen 4-Aminobiphenyl 46:97 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 9 30 theme adducts 1831:1837 arg1 number 1815:1820 the number 1811:1820 the number of ABPdG adducts 1811:1837 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 0 31 theme Carcinogen 72:81 arg1 4-Aminobiphenyl 83:97 the Human Carcinogen 4-Aminobiphenyl 62:97 the Human Carcinogen 4-Aminobiphenyl 62:97 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 9 32 gly heterogeneity 1866:1878 arg1 DNA 1895:1897 ABP-exposed DNA 1883:1897 ABP-exposed DNA 1883:1897 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 5 33 theme cigarette 896:904 arg1 smoke 906:910 cigarette smoke 896:910 cigarette smoke 896:910 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 3 34 theme Previous 332:339 arg1 work 341:344 Previous work 332:344 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) 332:408 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 3 35 theme single 366:371 arg1 adduct 384:389 a single AA-derived adduct 364:389 a single AA-derived adduct (monoadducted DNA) 364:408 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 3 35 theme single 366:371 arg1 DNA 405:407 monoadducted DNA 392:407 monoadducted DNA 392:407 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 5 36 located found 887:891 arg1 smoke 906:910 cigarette smoke 896:910 cigarette smoke 896:910 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 5 36 located found 887:891 arg1 dyes 923:926 select dyes 916:926 select dyes 916:926 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 5 36 located found 887:891 arg2 carcinogen 844:853 the potent bladder carcinogen 4-aminobiphenyl (ABP) 825:875 the potent bladder carcinogen 4-aminobiphenyl (ABP) 825:875 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 8 37 theme syn 1691:1693 arg1 preference 1695:1704 a greater syn preference 1681:1704 a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA 1681:1780 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 9 38 theme ABP-exposed 1883:1893 arg1 DNA 1895:1897 ABP-exposed DNA 1883:1897 ABP-exposed DNA 1883:1897 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 5 39 theme MD 755:756 arg1 simulations 758:768 quintuplet 0.5 μs MD simulations 737:768 quintuplet 0.5 μs MD simulations 737:768 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 7 40 theme lesion 1422:1427 arg1 [i.e. 1441:1445 the syn lesion orientation [i.e. 1414:1445 the syn lesion orientation [i.e. 1414:1445 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 9 41 from increase 1799:1806 arg1 number 1815:1820 the number 1811:1820 the number of ABPdG adducts 1811:1837 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 4 42 contain containing 604:613 arg1 DNA 600:602 DNA 600:602 DNA containing two bulky adducts (diadducted DNA) in close proximity 600:667 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 4 42 contain containing 604:613 arg2 adducts 625:631 two bulky adducts 615:631 two bulky adducts (diadducted DNA) 615:648 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 4 42 contain containing 604:613 arg2 DNA 645:647 diadducted DNA 634:647 diadducted DNA 634:647 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 8 43 from effects 1565:1571 arg1 heterogeneity 1595:1607 the conformational heterogeneity 1576:1607 the conformational heterogeneity 1576:1607 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 3 44 theme monoadducted 392:403 arg1 adduct 384:389 a single AA-derived adduct 364:389 a single AA-derived adduct (monoadducted DNA) 364:408 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 3 44 theme monoadducted 392:403 arg1 DNA 405:407 monoadducted DNA 392:407 monoadducted DNA 392:407 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 0 45 theme Local 20:24 arg1 Event 37:41 a Second Local DNA Damage Event 11:41 a Second Local DNA Damage Event 11:41 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 7 46 contain having 1314:1319 arg2 preference 1339:1348 the greatest anti preference 1321:1348 the greatest anti preference 1321:1348 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 7 46 contain having 1314:1319 arg1 site 1309:1312 the G1 site 1302:1312 the G1 site having the greatest anti preference 1302:1348 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 5 47 theme present 719:725 arg1 work 727:730 the present work 715:730 the present work 715:730 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 3 48 theme structure-function 422:439 arg1 relationship 441:452 a structure-function relationship 420:452 a structure-function relationship between the damaged DNA conformation and cellular outcomes 420:511 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 0 49 theme Damage 30:35 arg1 Event 37:41 a Second Local DNA Damage Event 11:41 a Second Local DNA Damage Event 11:41 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 6 50 from hotspot 1190:1196 arg1 combinations 1135:1146 all combinations 1131:1146 all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC) 1131:1219 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 1 51 theme aromatic 190:197 arg1 AAs 207:209 AAs 207:209 AAs 207:209 Exposure of humans to carcinogenic aromatic amines (AAs) occurs daily. 35147430 1 51 theme aromatic 190:197 arg1 amines 199:204 carcinogenic aromatic amines 177:204 carcinogenic aromatic amines (AAs) 177:210 Exposure of humans to carcinogenic aromatic amines (AAs) occurs daily. 35147430 7 52 theme helical 1379:1385 arg1 structures 1387:1396 helical structures 1379:1396 helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations] 1379:1506 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 3 53 theme damaged 466:472 arg1 conformation 478:489 the damaged DNA conformation 462:489 the damaged DNA conformation 462:489 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 0 54 dep Effects 0:6 arg1 Study 121:125 A Molecular Dynamics Study 100:125 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 0:153 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 6 55 theme unique 1003:1008 arg1 duplexes 1014:1021 18 unique DNA duplexes 1000:1021 18 unique DNA duplexes 1000:1021 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 0 56 theme Structure 144:152 arg1 Study 121:125 A Molecular Dynamics Study 100:125 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 0:153 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 8 57 theme Diadducted 1509:1518 arg1 DNA 1520:1522 Diadducted DNA 1509:1522 Diadducted DNA 1509:1522 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 6 58 theme G 1157:1157 arg1 positions 1159:1167 three G positions 1151:1167 three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC) 1151:1219 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 3 59 theme cellular 495:502 arg1 outcomes 504:511 cellular outcomes 495:511 cellular outcomes 495:511 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 7 60 theme greatest 1325:1332 arg1 preference 1339:1348 the greatest anti preference 1321:1348 the greatest anti preference 1321:1348 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 8 61 theme interesting 1535:1545 arg1 effects 1565:1571 interesting lesion separation effects 1535:1571 interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA 1535:1780 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 5 62 theme structural 788:797 arg1 impact 799:804 the structural impact 784:804 the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct 784:983 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 7 63 theme anti 1334:1337 arg1 preference 1339:1348 the greatest anti preference 1321:1348 the greatest anti preference 1321:1348 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 3 64 link AA-derived 373:382 arg1 adduct 384:389 a single AA-derived adduct 364:389 a single AA-derived adduct (monoadducted DNA) 364:408 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 3 64 link AA-derived 373:382 arg1 DNA 405:407 monoadducted DNA 392:407 monoadducted DNA 392:407 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 6 65 theme ABPdG 1065:1069 arg1 adducts 1071:1077 one or two ABPdG adducts 1054:1077 one or two ABPdG adducts 1054:1077 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 2 66 link N-linked 308:315 arg1 adducts 323:329 N-linked C8-dG adducts 308:329 N-linked C8-dG adducts 308:329 AAs are bioactivated in cells into products that attack DNA, primarily leading to N-linked C8-dG adducts. 35147430 8 67 theme separation 1554:1563 arg1 effects 1565:1571 interesting lesion separation effects 1535:1571 interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA 1535:1780 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 7 68 theme G1 1306:1307 arg1 site 1309:1312 the G1 site 1302:1312 the G1 site having the greatest anti preference 1302:1348 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 9 69 theme human 2015:2019 arg1 exposure 2021:2028 human exposure 2015:2028 human exposure to elevated levels of ABP 2015:2054 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 0 70 theme Dynamics 112:119 arg1 Study 121:125 A Molecular Dynamics Study 100:125 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 0:153 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 5 71 theme DNA 809:811 arg1 exposure 813:820 DNA exposure 809:820 DNA exposure 809:820 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 4 72 theme DNA 600:602 arg1 conformation 560:571 conformation 560:571 conformation 560:571 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 4 72 theme DNA 600:602 arg1 outcomes 588:595 biological outcomes 577:595 biological outcomes 577:595 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 5 73 theme bladder 836:842 arg1 carcinogen 844:853 the potent bladder carcinogen 4-aminobiphenyl (ABP) 825:875 the potent bladder carcinogen 4-aminobiphenyl (ABP) 825:875 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 7 74 theme sequence-dependent 1248:1265 arg1 heterogeneity 1282:1294 sequence-dependent conformational heterogeneity 1248:1294 sequence-dependent conformational heterogeneity 1248:1294 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 4 75 theme close 653:657 arg1 proximity 659:667 close proximity 653:667 close proximity 653:667 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 6 76 theme NarI 1176:1179 arg1 hotspot 1190:1196 the NarI mutation hotspot 1172:1196 the NarI mutation hotspot for AAs (5'-G1G2CG3CC) 1172:1219 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 5 77 link N-linked 963:970 arg1 adduct 978:983 the widely studied N-linked ABPdG adduct 944:983 the widely studied N-linked ABPdG adduct 944:983 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 6 78 theme syn 1098:1100 arg1 orientation 1113:1123 the anti and/or syn glycosidic orientation 1082:1123 orientation 1113:1123 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 9 79 theme ABP 2052:2054 arg1 levels 2042:2047 elevated levels 2033:2047 elevated levels of ABP 2033:2054 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 5 80 theme N-linked 963:970 arg1 adduct 978:983 the widely studied N-linked ABPdG adduct 944:983 the widely studied N-linked ABPdG adduct 944:983 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 8 81 theme anti 1630:1633 arg1 preference 1635:1644 a greater anti preference 1620:1644 a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA 1620:1780 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 5 82 theme exposure 813:820 arg1 impact 799:804 the structural impact 784:804 the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct 784:983 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 4 83 theme diadducted 634:643 arg1 adducts 625:631 two bulky adducts 615:631 two bulky adducts (diadducted DNA) 615:648 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 4 83 theme diadducted 634:643 arg1 DNA 645:647 diadducted DNA 634:647 diadducted DNA 634:647 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 9 84 theme ABPdG 1825:1829 arg1 adducts 1831:1837 ABPdG adducts 1825:1837 ABPdG adducts 1825:1837 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 0 85 theme Human 66:70 arg1 4-Aminobiphenyl 83:97 the Human Carcinogen 4-Aminobiphenyl 62:97 the Human Carcinogen 4-Aminobiphenyl 62:97 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 0 86 theme 4-Aminobiphenyl 83:97 arg1 Toxicity 50:57 the Toxicity 46:57 the Toxicity of the Human Carcinogen 4-Aminobiphenyl 46:97 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 9 87 theme conformational 1851:1864 arg1 heterogeneity 1866:1878 the conformational heterogeneity 1847:1878 the conformational heterogeneity of ABP-exposed DNA 1847:1897 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 9 87 theme conformational 1851:1864 arg1 result 1788:1793 a result 1786:1793 a result 1786:1793 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 5 88 dep carcinogen 844:853 arg1 ABP 872:874 ABP 872:874 ABP 872:874 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 5 88 dep carcinogen 844:853 arg1 4-aminobiphenyl 855:869 4-aminobiphenyl 855:869 the potent bladder carcinogen 4-aminobiphenyl (ABP) 825:875 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 5 89 theme current 683:689 arg1 void 691:694 this current void 678:694 this current void 678:694 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 5 90 theme quintuplet 737:746 arg1 simulations 758:768 quintuplet 0.5 μs MD simulations 737:768 quintuplet 0.5 μs MD simulations 737:768 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 3 91 from work 341:344 arg1 DNA 349:351 DNA 349:351 DNA containing a single AA-derived adduct (monoadducted DNA) 349:408 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 8 92 theme monoadducted 1765:1776 arg1 DNA 1778:1780 monoadducted DNA 1765:1780 monoadducted DNA 1765:1780 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 3 93 theme AA-derived 373:382 arg1 adduct 384:389 a single AA-derived adduct 364:389 a single AA-derived adduct (monoadducted DNA) 364:408 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 3 93 theme AA-derived 373:382 arg1 DNA 405:407 monoadducted DNA 392:407 monoadducted DNA 392:407 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 0 94 theme Second 13:18 arg1 Event 37:41 a Second Local DNA Damage Event 11:41 a Second Local DNA Damage Event 11:41 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 8 95 theme greater 1683:1689 arg1 preference 1695:1704 a greater syn preference 1681:1704 a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA 1681:1780 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 9 96 theme DNA 1895:1897 arg1 heterogeneity 1866:1878 the conformational heterogeneity 1847:1878 the conformational heterogeneity of ABP-exposed DNA 1847:1897 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 9 96 theme DNA 1895:1897 arg1 result 1788:1793 a result 1786:1793 a result 1786:1793 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 8 97 theme conformational 1580:1593 arg1 heterogeneity 1595:1607 the conformational heterogeneity 1576:1607 the conformational heterogeneity 1576:1607 Diadducted DNA results in interesting lesion separation effects on the conformational heterogeneity, including a greater anti preference for neighboring adducts (G1G2) and a greater syn preference for next-nearest neighbor damaged sites (G2G3) compared to monoadducted DNA. 35147430 2 98 theme C8-dG 317:321 arg1 adducts 323:329 N-linked C8-dG adducts 308:329 N-linked C8-dG adducts 308:329 AAs are bioactivated in cells into products that attack DNA, primarily leading to N-linked C8-dG adducts. 35147430 0 99 theme DNA 26:28 arg1 Event 37:41 a Second Local DNA Damage Event 11:41 a Second Local DNA Damage Event 11:41 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 7 100 theme orientation 1429:1439 arg1 [i.e. 1441:1445 the syn lesion orientation [i.e. 1414:1445 the syn lesion orientation [i.e. 1414:1445 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 0 101 theme Event 37:41 arg1 Effects 0:6 Effects 0:6 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 0:153 Effects of a Second Local DNA Damage Event on the Toxicity of the Human Carcinogen 4-Aminobiphenyl: A Molecular Dynamics Study of a Damaged DNA Structure. 35147430 7 102 theme syn 1418:1420 arg1 [i.e. 1441:1445 the syn lesion orientation [i.e. 1414:1445 the syn lesion orientation [i.e. 1414:1445 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 2 103 theme N-linked 308:315 arg1 adducts 323:329 N-linked C8-dG adducts 308:329 N-linked C8-dG adducts 308:329 AAs are bioactivated in cells into products that attack DNA, primarily leading to N-linked C8-dG adducts. 35147430 9 104 theme relative 1916:1923 arg1 positions 1925:1933 the relative positions 1912:1933 the relative positions of the lesions 1912:1948 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 2 105 theme attack 275:280 arg1 DNA 282:284 attack DNA 275:284 attack DNA 275:284 AAs are bioactivated in cells into products that attack DNA, primarily leading to N-linked C8-dG adducts. 35147430 7 106 theme structures 1387:1396 arg1 range 1370:1374 the range 1366:1374 the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations] 1366:1506 Monoadducted DNA displays sequence-dependent conformational heterogeneity, with the G1 site having the greatest anti preference, and highlights the range of helical structures associated with the syn lesion orientation [i.e., stacked (S), intercalated (I), and wedge (W) conformations]. 35147430 5 107 theme select 916:921 arg1 dyes 923:926 select dyes 916:926 select dyes 916:926 To fill this current void in the literature, the present work uses quintuplet 0.5 μs MD simulations to understand the structural impact of DNA exposure to the potent bladder carcinogen 4-aminobiphenyl (ABP), which is found in cigarette smoke and select dyes, and results in the widely studied N-linked ABPdG adduct. 35147430 6 108 theme DNA 1010:1012 arg1 duplexes 1014:1021 18 unique DNA duplexes 1000:1021 18 unique DNA duplexes 1000:1021 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35147430 4 109 theme biological 577:586 arg1 outcomes 588:595 biological outcomes 577:595 biological outcomes 577:595 However, relatively little is known about the conformation and biological outcomes of DNA containing two bulky adducts (diadducted DNA) in close proximity. 35147430 9 110 theme lesions 1942:1948 arg1 positions 1925:1933 the relative positions 1912:1933 the relative positions of the lesions 1912:1948 As a result, an increase in the number of ABPdG adducts changes the conformational heterogeneity of ABP-exposed DNA depending on the relative positions of the lesions and thereby could result in increased or decreased toxicity upon human exposure to elevated levels of ABP. 35147430 3 111 theme DNA 474:476 arg1 conformation 478:489 the damaged DNA conformation 462:489 the damaged DNA conformation 462:489 Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown a structure-function relationship between the damaged DNA conformation and cellular outcomes. 35147430 6 112 from positions 1159:1167 arg1 hotspot 1190:1196 the NarI mutation hotspot 1172:1196 the NarI mutation hotspot for AAs (5'-G1G2CG3CC) 1172:1219 Specifically, 18 unique DNA duplexes were investigated that contain one or two ABPdG adducts in the anti and/or syn glycosidic orientation(s) in all combinations of three G positions in the NarI mutation hotspot for AAs (5'-G1G2CG3CC). 35335708 4 0 theme in 765:766 arg1 functionality 773:785 in situ functionality 765:785 in situ functionality 765:785 Moreover, different silanes were added to the sol/gel process to introduce in situ functionality to the CNF/silica hydrogels. 35335708 1 1 theme surface 186:192 arg1 areas 194:198 extremely large specific surface areas 161:198 extremely large specific surface areas 161:198 Nanoporous silica gels feature extremely large specific surface areas and high porosities and are ideal candidates for adsorption-related processes, although they are commonly rather fragile. 35335708 6 2 theme sol/gel 988:994 arg1 process 996:1002 The developed solvent-free sol/gel process 961:1002 The developed solvent-free sol/gel process 961:1002 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 6 3 theme solvent-free 975:986 arg1 process 996:1002 The developed solvent-free sol/gel process 961:1002 The developed solvent-free sol/gel process 961:1002 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 4 4 dep in 765:766 arg1 situ 768:771 situ 768:771 situ 768:771 Moreover, different silanes were added to the sol/gel process to introduce in situ functionality to the CNF/silica hydrogels. 35335708 2 5 dep novel 364:368 arg1 solvent-free 382:393 solvent-free 382:393 solvent-free 382:393 To overcome this obstacle, we developed a novel, completely solvent-free process to prepare mechanically robust CNF-reinforced silica nanocomposites via the incorporation of methylcellulose and starch. 35335708 0 6 theme Soluble 105:111 arg1 Polysaccharides 113:127 Soluble Polysaccharides 105:127 Soluble Polysaccharides 105:127 Facile Preparation of Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels Reinforced with Soluble Polysaccharides. 35335708 6 7 theme developed 965:973 arg1 process 996:1002 The developed solvent-free sol/gel process 961:1002 The developed solvent-free sol/gel process 961:1002 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 3 8 theme compressive 613:623 arg1 strength 625:632 the compressive strength 609:632 the compressive strength 609:632 Significantly, the addition of starch was very promising and substantially increased the compressive strength while preserving the specific surface area of the gels. 35335708 5 9 theme heavy 938:942 arg1 metals 944:949 heavy metals 938:949 heavy metals 938:949 Thereby, CNF/silica hydrogels bearing carboxyl groups and thiol groups were produced and tested as adsorber materials for heavy metals and dyes. 35335708 6 10 theme functionalities 1115:1129 arg1 introduction 1090:1101 the introduction 1086:1101 the introduction of chemical functionalities 1086:1129 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 2 11 theme CNF-reinforced 434:447 arg1 nanocomposites 456:469 mechanically robust CNF-reinforced silica nanocomposites 414:469 mechanically robust CNF-reinforced silica nanocomposites 414:469 To overcome this obstacle, we developed a novel, completely solvent-free process to prepare mechanically robust CNF-reinforced silica nanocomposites via the incorporation of methylcellulose and starch. 35335708 2 12 theme starch 516:521 arg1 incorporation 479:491 the incorporation 475:491 the incorporation of methylcellulose and starch 475:521 To overcome this obstacle, we developed a novel, completely solvent-free process to prepare mechanically robust CNF-reinforced silica nanocomposites via the incorporation of methylcellulose and starch. 35335708 0 13 theme Facile 0:5 arg1 Preparation 7:17 Facile Preparation 0:17 Facile Preparation of Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels 0:87 Facile Preparation of Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels Reinforced with Soluble Polysaccharides. 35335708 1 14 theme high 204:207 arg1 porosities 209:218 high porosities 204:218 high porosities 204:218 Nanoporous silica gels feature extremely large specific surface areas and high porosities and are ideal candidates for adsorption-related processes, although they are commonly rather fragile. 35335708 6 15 theme materials 1176:1184 arg1 scope 1162:1166 the application scope 1146:1166 the application scope of such materials 1146:1184 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 4 16 theme sol/gel 736:742 arg1 process 744:750 the sol/gel process 732:750 the sol/gel process 732:750 Moreover, different silanes were added to the sol/gel process to introduce in situ functionality to the CNF/silica hydrogels. 35335708 2 17 theme methylcellulose 496:510 arg1 incorporation 479:491 the incorporation 475:491 the incorporation of methylcellulose and starch 475:521 To overcome this obstacle, we developed a novel, completely solvent-free process to prepare mechanically robust CNF-reinforced silica nanocomposites via the incorporation of methylcellulose and starch. 35335708 4 18 theme CNF/silica 794:803 arg1 hydrogels 805:813 the CNF/silica hydrogels 790:813 the CNF/silica hydrogels 790:813 Moreover, different silanes were added to the sol/gel process to introduce in situ functionality to the CNF/silica hydrogels. 35335708 6 19 theme mechanical 1055:1064 arg1 strength 1066:1073 high mechanical strength 1050:1073 high mechanical strength 1050:1073 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 6 20 theme such 1171:1174 arg1 materials 1176:1184 such materials 1171:1184 such materials 1171:1184 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 4 21 theme different 700:708 arg1 silanes 710:716 different silanes 700:716 different silanes 700:716 Moreover, different silanes were added to the sol/gel process to introduce in situ functionality to the CNF/silica hydrogels. 35335708 6 22 theme high 1050:1053 arg1 strength 1066:1073 high mechanical strength 1050:1073 high mechanical strength 1050:1073 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 1 23 theme Nanoporous 130:139 arg1 gels 148:151 Nanoporous silica gels 130:151 Nanoporous silica gels 130:151 Nanoporous silica gels feature extremely large specific surface areas and high porosities and are ideal candidates for adsorption-related processes, although they are commonly rather fragile. 35335708 1 24 theme ideal 228:232 arg1 candidates 234:243 ideal candidates 228:243 ideal candidates for adsorption-related processes 228:276 Nanoporous silica gels feature extremely large specific surface areas and high porosities and are ideal candidates for adsorption-related processes, although they are commonly rather fragile. 35335708 5 25 theme carboxyl 854:861 arg1 groups 863:868 carboxyl groups 854:868 carboxyl groups 854:868 Thereby, CNF/silica hydrogels bearing carboxyl groups and thiol groups were produced and tested as adsorber materials for heavy metals and dyes. 35335708 3 26 theme starch 555:560 arg1 promising 571:579 promising 571:579 promising 571:579 Significantly, the addition of starch was very promising and substantially increased the compressive strength while preserving the specific surface area of the gels. 35335708 3 26 theme starch 555:560 arg1 addition 543:550 the addition 539:550 the addition of starch 539:560 Significantly, the addition of starch was very promising and substantially increased the compressive strength while preserving the specific surface area of the gels. 35335708 5 27 theme adsorber 915:922 arg1 materials 924:932 adsorber materials 915:932 adsorber materials for heavy metals and dyes 915:958 Thereby, CNF/silica hydrogels bearing carboxyl groups and thiol groups were produced and tested as adsorber materials for heavy metals and dyes. 35335708 5 27 theme adsorber 915:922 arg1 hydrogels 836:844 CNF/silica hydrogels 825:844 CNF/silica hydrogels bearing carboxyl groups and thiol groups 825:885 Thereby, CNF/silica hydrogels bearing carboxyl groups and thiol groups were produced and tested as adsorber materials for heavy metals and dyes. 35335708 0 28 theme Robust 35:40 arg1 Gels 84:87 Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels 22:87 Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels 22:87 Facile Preparation of Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels Reinforced with Soluble Polysaccharides. 35335708 2 29 theme silica 449:454 arg1 nanocomposites 456:469 mechanically robust CNF-reinforced silica nanocomposites 414:469 mechanically robust CNF-reinforced silica nanocomposites 414:469 To overcome this obstacle, we developed a novel, completely solvent-free process to prepare mechanically robust CNF-reinforced silica nanocomposites via the incorporation of methylcellulose and starch. 35335708 0 30 theme Silica/Cellulose 57:72 arg1 Gels 84:87 Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels 22:87 Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels 22:87 Facile Preparation of Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels Reinforced with Soluble Polysaccharides. 35335708 6 31 theme CNF/silica 1024:1033 arg1 hydrogels 1035:1043 shapable 3D CNF/silica hydrogels 1012:1043 shapable 3D CNF/silica hydrogels 1012:1043 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 5 32 theme thiol 874:878 arg1 groups 880:885 thiol groups 874:885 thiol groups 874:885 Thereby, CNF/silica hydrogels bearing carboxyl groups and thiol groups were produced and tested as adsorber materials for heavy metals and dyes. 35335708 5 33 theme CNF/silica 825:834 arg1 materials 924:932 adsorber materials 915:932 adsorber materials for heavy metals and dyes 915:958 Thereby, CNF/silica hydrogels bearing carboxyl groups and thiol groups were produced and tested as adsorber materials for heavy metals and dyes. 35335708 5 33 theme CNF/silica 825:834 arg1 hydrogels 836:844 CNF/silica hydrogels 825:844 CNF/silica hydrogels bearing carboxyl groups and thiol groups 825:885 Thereby, CNF/silica hydrogels bearing carboxyl groups and thiol groups were produced and tested as adsorber materials for heavy metals and dyes. 35335708 3 34 theme specific 655:662 arg1 area 672:675 the specific surface area 651:675 the specific surface area of the gels 651:687 Significantly, the addition of starch was very promising and substantially increased the compressive strength while preserving the specific surface area of the gels. 35335708 1 35 theme silica 141:146 arg1 gels 148:151 Nanoporous silica gels 130:151 Nanoporous silica gels 130:151 Nanoporous silica gels feature extremely large specific surface areas and high porosities and are ideal candidates for adsorption-related processes, although they are commonly rather fragile. 35335708 0 36 theme Functional 46:55 arg1 Gels 84:87 Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels 22:87 Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels 22:87 Facile Preparation of Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels Reinforced with Soluble Polysaccharides. 35335708 6 37 theme 3D 1021:1022 arg1 hydrogels 1035:1043 shapable 3D CNF/silica hydrogels 1012:1043 shapable 3D CNF/silica hydrogels 1012:1043 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 3 38 theme surface 664:670 arg1 area 672:675 the specific surface area 651:675 the specific surface area of the gels 651:687 Significantly, the addition of starch was very promising and substantially increased the compressive strength while preserving the specific surface area of the gels. 35335708 2 39 theme novel 364:368 arg1 process 395:401 a novel, completely solvent-free process 362:401 a novel, completely solvent-free process to prepare mechanically robust CNF-reinforced silica nanocomposites via the incorporation of methylcellulose and starch 362:521 To overcome this obstacle, we developed a novel, completely solvent-free process to prepare mechanically robust CNF-reinforced silica nanocomposites via the incorporation of methylcellulose and starch. 35335708 6 40 theme shapable 1012:1019 arg1 hydrogels 1035:1043 shapable 3D CNF/silica hydrogels 1012:1043 shapable 3D CNF/silica hydrogels 1012:1043 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 1 41 theme adsorption-related 249:266 arg1 processes 268:276 adsorption-related processes 249:276 adsorption-related processes 249:276 Nanoporous silica gels feature extremely large specific surface areas and high porosities and are ideal candidates for adsorption-related processes, although they are commonly rather fragile. 35335708 6 42 theme chemical 1106:1113 arg1 functionalities 1115:1129 chemical functionalities 1106:1129 chemical functionalities 1106:1129 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 0 43 theme Gels 84:87 arg1 Preparation 7:17 Facile Preparation 0:17 Facile Preparation of Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels 0:87 Facile Preparation of Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels Reinforced with Soluble Polysaccharides. 35335708 6 44 theme application 1150:1160 arg1 scope 1162:1166 the application scope 1146:1166 the application scope of such materials 1146:1184 The developed solvent-free sol/gel process yielded shapable 3D CNF/silica hydrogels with high mechanical strength; moreover, the introduction of chemical functionalities further widens the application scope of such materials. 35335708 1 45 theme large 171:175 arg1 areas 194:198 extremely large specific surface areas 161:198 extremely large specific surface areas 161:198 Nanoporous silica gels feature extremely large specific surface areas and high porosities and are ideal candidates for adsorption-related processes, although they are commonly rather fragile. 35335708 2 46 theme robust 427:432 arg1 nanocomposites 456:469 mechanically robust CNF-reinforced silica nanocomposites 414:469 mechanically robust CNF-reinforced silica nanocomposites 414:469 To overcome this obstacle, we developed a novel, completely solvent-free process to prepare mechanically robust CNF-reinforced silica nanocomposites via the incorporation of methylcellulose and starch. 35335708 0 47 theme Nanofiber 74:82 arg1 Gels 84:87 Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels 22:87 Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels 22:87 Facile Preparation of Mechanically Robust and Functional Silica/Cellulose Nanofiber Gels Reinforced with Soluble Polysaccharides. 35335708 3 48 theme gels 684:687 arg1 area 672:675 the specific surface area 651:675 the specific surface area of the gels 651:687 Significantly, the addition of starch was very promising and substantially increased the compressive strength while preserving the specific surface area of the gels. 35335708 1 49 theme specific 177:184 arg1 areas 194:198 extremely large specific surface areas 161:198 extremely large specific surface areas 161:198 Nanoporous silica gels feature extremely large specific surface areas and high porosities and are ideal candidates for adsorption-related processes, although they are commonly rather fragile. 37000485 0 0 theme Mass 168:171 arg1 Spectrometry 173:184 Native Mass Spectrometry 161:184 Native Mass Spectrometry 161:184 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 0 1 from Glycoengineering 140:155 arg1 Insights 126:133 Insights 126:133 Insights from Glycoengineering and Native Mass Spectrometry 126:184 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 3 2 theme mass 535:538 arg1 spectrometry 540:551 high-resolution native mass spectrometry 512:551 high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes 512:653 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 3 2 theme mass 535:538 arg1 MS 554:555 MS 554:555 MS 554:555 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 5 3 theme % 835:835 arg1 occupancy 837:845 >90% occupancy 832:845 >90% occupancy 832:845 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 2 4 with interactions 397:408 arg1 Spike 415:419 Spike 415:419 Spike 415:419 Yet, questions remain as to the impact of glycans on mediating ACE2 dimerization and downstream interactions with Spike. 37000485 8 5 theme dimeric 1175:1181 arg1 ACE2 1183:1186 glycosylated dimeric ACE2 and Spike trimers 1162:1204 ACE2 1183:1186 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 9 6 theme positive 1387:1394 arg1 cooperativity 1396:1408 positive cooperativity 1387:1408 positive cooperativity 1387:1408 Comparing these values indicates that positive cooperativity may drive ACE2 dimers to complex with multiple Spike trimers. 37000485 8 7 gly glycosylated 1162:1173 arg1 ACE2 1183:1186 glycosylated dimeric ACE2 and Spike trimers 1162:1204 ACE2 1183:1186 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 3 8 theme N-glycan 587:594 arg1 occupancy 596:604 N-glycan occupancy 587:604 N-glycan occupancy 587:604 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 1 9 theme Spike 223:227 arg1 protein 229:235 the SARS-CoV-2 Spike protein 208:235 the SARS-CoV-2 Spike protein 208:235 Interactions between the SARS-CoV-2 Spike protein and ACE2 are one of the most scrutinized reactions of our time. 37000485 10 10 theme regulatory 1523:1532 arg1 role 1534:1537 a key regulatory role 1517:1537 a key regulatory role 1517:1537 Overall, our results show that occupancy has a key regulatory role in mediating interactions between ACE2 dimers and Spike trimers. 37000485 9 11 theme ACE2 1420:1423 arg1 dimers 1425:1430 ACE2 dimers 1420:1430 ACE2 dimers 1420:1430 Comparing these values indicates that positive cooperativity may drive ACE2 dimers to complex with multiple Spike trimers. 37000485 11 12 theme molecular 1823:1831 arg1 details 1833:1839 molecular details 1823:1839 molecular details important for developing strategies for neutralizing the virus 1823:1902 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 11 12 theme molecular 1823:1831 arg1 importance 1698:1707 the importance 1694:1707 the importance of glycosylation in ACE2 dimerization 1694:1745 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 11 12 theme molecular 1823:1831 arg1 propensity 1755:1764 the propensity 1751:1764 the propensity for Spike and ACE2 to assemble into higher oligomers 1751:1817 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 8 13 theme multiple 1226:1233 arg1 Spike2-ACE2 1267:1277 Spike2-ACE2 1267:1277 Spike2-ACE2 1267:1277 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 8 13 theme multiple 1226:1233 arg1 Spike-ACE2 1252:1261 Spike-ACE2 1252:1261 Spike-ACE2 1252:1261 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 8 13 theme multiple 1226:1233 arg1 stoichiometries 1235:1249 multiple stoichiometries 1226:1249 multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) 1226:1278 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 4 14 theme Spike 681:685 arg1 trimers 687:693 intact Spike trimers 674:693 intact Spike trimers 674:693 We confirmed that intact Spike trimers have all 66 N-linked sites occupied. 37000485 0 15 theme Cooperative 49:59 arg1 Assembly 61:68 the Cooperative Assembly 45:68 the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes 45:123 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 0 16 from Role 15:18 arg1 Assembly 61:68 the Cooperative Assembly 45:68 the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes 45:123 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 9 17 theme Spike 1457:1461 arg1 trimers 1463:1469 multiple Spike trimers 1448:1469 multiple Spike trimers 1448:1469 Comparing these values indicates that positive cooperativity may drive ACE2 dimers to complex with multiple Spike trimers. 37000485 9 18 with complex 1435:1441 arg1 trimers 1463:1469 multiple Spike trimers 1448:1469 multiple Spike trimers 1448:1469 Comparing these values indicates that positive cooperativity may drive ACE2 dimers to complex with multiple Spike trimers. 37000485 11 19 theme SARS-CoV-2 1665:1674 arg1 site 1688:1691 an intact SARS-CoV-2 interaction site 1655:1691 an intact SARS-CoV-2 interaction site 1655:1691 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 7 20 theme site-directed 1116:1128 arg1 mutagenesis 1130:1140 site-directed mutagenesis 1116:1140 site-directed mutagenesis 1116:1140 Unexpectedly, we found that Asn432 plays a role in mediating dimerization, a result confirmed by site-directed mutagenesis. 37000485 11 21 dep propensity 1755:1764 arg1 assemble 1788:1795 assemble 1788:1795 to assemble into higher oligomers 1785:1817 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 8 22 theme dissociation 1285:1296 arg1 Kds 1309:1311 Kds 1309:1311 Kds 1309:1311 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 8 22 theme dissociation 1285:1296 arg1 constants 1298:1306 dissociation constants 1285:1306 dissociation constants (Kds) of ∼500 and <100 nM, respectively 1285:1346 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 5 23 theme monomeric 736:744 arg1 ACE2 746:749 monomeric ACE2 736:749 monomeric ACE2 736:749 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 0 24 theme Occupancy 32:40 arg1 Role 15:18 the Role 11:18 the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes 11:123 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 9 25 theme multiple 1448:1455 arg1 trimers 1463:1469 multiple Spike trimers 1448:1469 multiple Spike trimers 1448:1469 Comparing these values indicates that positive cooperativity may drive ACE2 dimers to complex with multiple Spike trimers. 37000485 6 26 from glycoforms 932:941 arg1 ACE2 946:949 ACE2 946:949 ACE2 946:949 By resolving the glycoforms on ACE2, we deciphered the influence of each N-glycan on ACE2 dimerization. 37000485 11 27 from propensity 1755:1764 arg1 dimerization 1734:1745 ACE2 dimerization 1729:1745 ACE2 dimerization 1729:1745 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 1 28 theme scrutinized 266:276 arg1 reactions 278:286 the most scrutinized reactions 257:286 the most scrutinized reactions of our time 257:298 Interactions between the SARS-CoV-2 Spike protein and ACE2 are one of the most scrutinized reactions of our time. 37000485 3 29 from impact 577:582 arg1 assembly 613:620 the assembly 609:620 the assembly of multiple Spike-ACE2 complexes 609:653 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 11 30 theme important 1841:1849 arg1 details 1833:1839 molecular details 1823:1839 molecular details important for developing strategies for neutralizing the virus 1823:1902 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 11 30 theme important 1841:1849 arg1 importance 1698:1707 the importance 1694:1707 the importance of glycosylation in ACE2 dimerization 1694:1745 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 11 30 theme important 1841:1849 arg1 propensity 1755:1764 the propensity 1751:1764 the propensity for Spike and ACE2 to assemble into higher oligomers 1751:1817 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 5 31 dep occupied 898:905 arg1 % 911:911 ∼30% 908:911 ∼30% 908:911 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 3 32 theme complexes 645:653 arg1 assembly 613:620 the assembly 609:620 the assembly of multiple Spike-ACE2 complexes 609:653 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 10 33 theme Spike 1589:1593 arg1 trimers 1595:1601 Spike trimers 1589:1601 Spike trimers 1589:1601 Overall, our results show that occupancy has a key regulatory role in mediating interactions between ACE2 dimers and Spike trimers. 37000485 0 34 theme N-Glycan 23:30 arg1 Occupancy 32:40 N-Glycan Occupancy 23:40 N-Glycan Occupancy 23:40 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 1 35 theme time 295:298 arg1 reactions 278:286 the most scrutinized reactions 257:286 the most scrutinized reactions of our time 257:298 Interactions between the SARS-CoV-2 Spike protein and ACE2 are one of the most scrutinized reactions of our time. 37000485 5 36 theme glycan 771:776 arg1 sites 778:782 all seven N-linked glycan sites 752:782 all seven N-linked glycan sites 752:782 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 10 37 contain has 1513:1515 arg1 occupancy 1503:1511 occupancy 1503:1511 occupancy 1503:1511 Overall, our results show that occupancy has a key regulatory role in mediating interactions between ACE2 dimers and Spike trimers. 37000485 10 37 contain has 1513:1515 arg2 role 1534:1537 a key regulatory role 1517:1537 a key regulatory role 1517:1537 Overall, our results show that occupancy has a key regulatory role in mediating interactions between ACE2 dimers and Spike trimers. 37000485 3 38 theme multiple 625:632 arg1 complexes 645:653 multiple Spike-ACE2 complexes 625:653 multiple Spike-ACE2 complexes 625:653 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 6 39 gly glycoforms 932:941 arg2 ACE2 946:949 ACE2 946:949 ACE2 946:949 By resolving the glycoforms on ACE2, we deciphered the influence of each N-glycan on ACE2 dimerization. 37000485 8 40 dep stoichiometries 1235:1249 arg1 Spike2-ACE2 1267:1277 Spike2-ACE2 1267:1277 Spike2-ACE2 1267:1277 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 8 40 dep stoichiometries 1235:1249 arg1 Spike-ACE2 1252:1261 Spike-ACE2 1252:1261 Spike-ACE2 1252:1261 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 8 40 dep stoichiometries 1235:1249 arg1 stoichiometries 1235:1249 multiple stoichiometries 1226:1249 multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) 1226:1278 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 5 41 used occupied 898:905 arg2 Asn690 872:877 Asn690 872:877 Asn690 872:877 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 5 41 used occupied 898:905 arg2 site 866:869 the seventh site 854:869 the seventh site (Asn690) 854:878 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 5 42 used occupied 788:795 arg2 sites 778:782 all seven N-linked glycan sites 752:782 all seven N-linked glycan sites 752:782 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 2 43 theme glycans 343:349 arg1 impact 333:338 the impact 329:338 the impact of glycans on mediating ACE2 dimerization and downstream interactions with Spike 329:419 Yet, questions remain as to the impact of glycans on mediating ACE2 dimerization and downstream interactions with Spike. 37000485 0 44 dep Uncovering 0:9 arg1 Insights 126:133 Insights 126:133 Insights from Glycoengineering and Native Mass Spectrometry 126:184 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 4 45 contain have 695:698 arg1 trimers 687:693 intact Spike trimers 674:693 intact Spike trimers 674:693 We confirmed that intact Spike trimers have all 66 N-linked sites occupied. 37000485 4 45 contain have 695:698 arg2 sites 716:720 all 66 N-linked sites 700:720 all 66 N-linked sites occupied 700:729 We confirmed that intact Spike trimers have all 66 N-linked sites occupied. 37000485 3 46 theme glycoengineering 481:496 arg1 strategy 498:505 a glycoengineering strategy 479:505 a glycoengineering strategy 479:505 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 2 47 with dimerization 369:380 arg1 Spike 415:419 Spike 415:419 Spike 415:419 Yet, questions remain as to the impact of glycans on mediating ACE2 dimerization and downstream interactions with Spike. 37000485 4 48 link N-linked 707:714 arg1 sites 716:720 all 66 N-linked sites 700:720 all 66 N-linked sites occupied 700:729 We confirmed that intact Spike trimers have all 66 N-linked sites occupied. 37000485 3 49 theme native 528:533 arg1 spectrometry 540:551 high-resolution native mass spectrometry 512:551 high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes 512:653 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 3 49 theme native 528:533 arg1 MS 554:555 MS 554:555 MS 554:555 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 5 50 theme >90 832:834 arg1 % 835:835 % 835:835 % 835:835 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 11 51 from importance 1698:1707 arg1 dimerization 1734:1745 ACE2 dimerization 1729:1745 ACE2 dimerization 1729:1745 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 10 52 theme key 1519:1521 arg1 role 1534:1537 a key regulatory role 1517:1537 a key regulatory role 1517:1537 Overall, our results show that occupancy has a key regulatory role in mediating interactions between ACE2 dimers and Spike trimers. 37000485 8 53 theme glycosylated 1162:1173 arg1 ACE2 1183:1186 glycosylated dimeric ACE2 and Spike trimers 1162:1204 ACE2 1183:1186 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 11 54 theme glycosylation 1712:1724 arg1 details 1833:1839 molecular details 1823:1839 molecular details important for developing strategies for neutralizing the virus 1823:1902 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 11 54 theme glycosylation 1712:1724 arg1 importance 1698:1707 the importance 1694:1707 the importance of glycosylation in ACE2 dimerization 1694:1745 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 11 54 theme glycosylation 1712:1724 arg1 propensity 1755:1764 the propensity 1751:1764 the propensity for Spike and ACE2 to assemble into higher oligomers 1751:1817 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 0 55 theme Complexes 115:123 arg1 Assembly 61:68 the Cooperative Assembly 45:68 the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes 45:123 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 6 56 from influence 970:978 arg1 dimerization 1005:1016 ACE2 dimerization 1000:1016 ACE2 dimerization 1000:1016 By resolving the glycoforms on ACE2, we deciphered the influence of each N-glycan on ACE2 dimerization. 37000485 1 57 theme SARS-CoV-2 212:221 arg1 protein 229:235 the SARS-CoV-2 Spike protein 208:235 the SARS-CoV-2 Spike protein 208:235 Interactions between the SARS-CoV-2 Spike protein and ACE2 are one of the most scrutinized reactions of our time. 37000485 8 58 theme Spike 1192:1196 arg1 trimers 1198:1204 glycosylated dimeric ACE2 and Spike trimers 1162:1204 trimers 1198:1204 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 5 59 link N-linked 762:769 arg1 sites 778:782 all seven N-linked glycan sites 752:782 all seven N-linked glycan sites 752:782 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 11 60 theme ACE2 1729:1732 arg1 dimerization 1734:1745 ACE2 dimerization 1729:1745 ACE2 dimerization 1729:1745 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 0 61 theme Native 161:166 arg1 Spectrometry 173:184 Native Mass Spectrometry 161:184 Native Mass Spectrometry 161:184 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 4 62 theme N-linked 707:714 arg1 sites 716:720 all 66 N-linked sites 700:720 all 66 N-linked sites occupied 700:729 We confirmed that intact Spike trimers have all 66 N-linked sites occupied. 37000485 11 63 theme intact 1658:1663 arg1 site 1688:1691 an intact SARS-CoV-2 interaction site 1655:1691 an intact SARS-CoV-2 interaction site 1655:1691 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 3 64 theme occupancy 596:604 arg1 impact 577:582 the impact 573:582 the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes 573:653 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 4 65 theme intact 674:679 arg1 trimers 687:693 intact Spike trimers 674:693 intact Spike trimers 674:693 We confirmed that intact Spike trimers have all 66 N-linked sites occupied. 37000485 0 66 theme Spike 73:77 arg1 Complexes 115:123 Spike and Angiotensin Converting Enzyme 2 Complexes 73:123 Spike and Angiotensin Converting Enzyme 2 Complexes 73:123 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 5 67 theme seventh 858:864 arg1 Asn690 872:877 Asn690 872:877 Asn690 872:877 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 5 67 theme seventh 858:864 arg1 site 866:869 the seventh site 854:869 the seventh site (Asn690) 854:878 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 0 68 theme Angiotensin 83:93 arg1 Enzyme 106:111 Angiotensin Converting Enzyme 2 83:113 Angiotensin Converting Enzyme 2 83:113 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 11 69 theme interaction 1676:1686 arg1 site 1688:1691 an intact SARS-CoV-2 interaction site 1655:1691 an intact SARS-CoV-2 interaction site 1655:1691 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 0 70 theme Enzyme 106:111 arg1 Complexes 115:123 Spike and Angiotensin Converting Enzyme 2 Complexes 73:123 Spike and Angiotensin Converting Enzyme 2 Complexes 73:123 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 6 71 theme ACE2 1000:1003 arg1 dimerization 1005:1016 ACE2 dimerization 1000:1016 ACE2 dimerization 1000:1016 By resolving the glycoforms on ACE2, we deciphered the influence of each N-glycan on ACE2 dimerization. 37000485 2 72 theme downstream 386:395 arg1 interactions 397:408 downstream interactions 386:408 downstream interactions with Spike 386:419 Yet, questions remain as to the impact of glycans on mediating ACE2 dimerization and downstream interactions with Spike. 37000485 5 73 contain have 827:830 arg1 sites 821:825 six sites 817:825 six sites 817:825 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 5 73 contain have 827:830 arg2 occupancy 837:845 >90% occupancy 832:845 >90% occupancy 832:845 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 2 74 theme ACE2 364:367 arg1 dimerization 369:380 ACE2 dimerization 364:380 ACE2 dimerization 364:380 Yet, questions remain as to the impact of glycans on mediating ACE2 dimerization and downstream interactions with Spike. 37000485 6 75 theme N-glycan 988:995 arg1 influence 970:978 the influence 966:978 the influence of each N-glycan on ACE2 dimerization 966:1016 By resolving the glycoforms on ACE2, we deciphered the influence of each N-glycan on ACE2 dimerization. 37000485 11 76 theme higher 1802:1807 arg1 oligomers 1809:1817 higher oligomers 1802:1817 higher oligomers 1802:1817 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 5 77 theme various 800:806 arg1 degrees 808:814 various degrees 800:814 various degrees 800:814 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 1 78 theme reactions 278:286 arg1 reactions 278:286 the most scrutinized reactions 257:286 the most scrutinized reactions of our time 257:298 Interactions between the SARS-CoV-2 Spike protein and ACE2 are one of the most scrutinized reactions of our time. 37000485 1 78 theme reactions 278:286 arg1 one 250:252 one 250:252 one 250:252 Interactions between the SARS-CoV-2 Spike protein and ACE2 are one of the most scrutinized reactions of our time. 37000485 0 79 from Spectrometry 173:184 arg1 Insights 126:133 Insights 126:133 Insights from Glycoengineering and Native Mass Spectrometry 126:184 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 3 80 theme Spike-ACE2 634:643 arg1 complexes 645:653 multiple Spike-ACE2 complexes 625:653 multiple Spike-ACE2 complexes 625:653 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 3 81 theme unanswered 445:454 arg1 questions 456:464 these unanswered questions 439:464 these unanswered questions 439:464 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 5 82 theme N-linked 762:769 arg1 sites 778:782 all seven N-linked glycan sites 752:782 all seven N-linked glycan sites 752:782 For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). 37000485 8 83 with complexes 1211:1219 arg1 Spike2-ACE2 1267:1277 Spike2-ACE2 1267:1277 Spike2-ACE2 1267:1277 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 8 83 with complexes 1211:1219 arg1 Spike-ACE2 1252:1261 Spike-ACE2 1252:1261 Spike-ACE2 1252:1261 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 8 83 with complexes 1211:1219 arg1 stoichiometries 1235:1249 multiple stoichiometries 1226:1249 multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) 1226:1278 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 0 84 theme Converting 95:104 arg1 Enzyme 106:111 Angiotensin Converting Enzyme 2 83:113 Angiotensin Converting Enzyme 2 83:113 Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry. 37000485 11 85 theme soluble 1626:1632 arg1 ACE2 1634:1637 soluble ACE2 1626:1637 soluble ACE2 (sACE2) 1626:1645 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 11 85 theme soluble 1626:1632 arg1 sACE2 1640:1644 sACE2 1640:1644 sACE2 1640:1644 More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus. 37000485 8 86 theme nM 1331:1332 arg1 Kds 1309:1311 Kds 1309:1311 Kds 1309:1311 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 8 86 theme nM 1331:1332 arg1 constants 1298:1306 dissociation constants 1285:1306 dissociation constants (Kds) of ∼500 and <100 nM, respectively 1285:1346 We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. 37000485 10 87 theme ACE2 1573:1576 arg1 dimers 1578:1583 ACE2 dimers 1573:1583 ACE2 dimers 1573:1583 Overall, our results show that occupancy has a key regulatory role in mediating interactions between ACE2 dimers and Spike trimers. 37000485 3 88 theme high-resolution 512:526 arg1 spectrometry 540:551 high-resolution native mass spectrometry 512:551 high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes 512:653 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 37000485 3 88 theme high-resolution 512:526 arg1 MS 554:555 MS 554:555 MS 554:555 Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. 36756538 3 0 theme 1-Da 317:320 arg1 tag 327:329 The 1-Da mass tag 313:329 The 1-Da mass tag created by this process 313:353 The 1-Da mass tag created by this process is observable by liquid chromatography-tandem mass spectrometry analysis. 36756538 3 0 theme 1-Da 317:320 arg1 observable 358:367 observable 358:367 observable 358:367 The 1-Da mass tag created by this process is observable by liquid chromatography-tandem mass spectrometry analysis. 36756538 4 1 theme chemical 508:515 arg1 interference 441:452 A potential interference 429:452 A potential interference to this method of N-glycosylation site mapping 429:499 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 4 1 theme chemical 508:515 arg1 deamidation 517:527 the chemical deamidation 504:527 the chemical deamidation 504:527 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 6 2 theme n-Asp 974:978 arg1 residue 980:986 an n-Asp residue 971:986 an n-Asp residue within the consensus sequence Asn-X-Ser/Thr 971:1030 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 4 3 theme false 591:595 arg1 positives 597:605 false positives 591:605 false positives 591:605 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 3 4 theme mass 322:325 arg1 tag 327:329 The 1-Da mass tag 313:329 The 1-Da mass tag created by this process 313:353 The 1-Da mass tag created by this process is observable by liquid chromatography-tandem mass spectrometry analysis. 36756538 3 4 theme mass 322:325 arg1 observable 358:367 observable 358:367 observable 358:367 The 1-Da mass tag created by this process is observable by liquid chromatography-tandem mass spectrometry analysis. 36756538 4 5 theme Asn 532:534 arg1 residues 536:543 Asn residues 532:543 Asn residues 532:543 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 1 6 theme deamidated 157:166 arg1 sites 168:172 deamidated sites 157:172 deamidated sites 157:172 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 1 7 theme current 56:62 arg1 method 64:69 A current method 54:69 A current method to locate sites of N-linked glycosylation on a protein 54:124 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 6 8 theme i-Asp 1134:1138 arg1 presence 1112:1119 the presence 1108:1119 the presence of n-Asp and i-Asp 1108:1138 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 4 9 theme mapping 493:499 arg1 method 462:467 this method 457:467 this method of N-glycosylation site mapping 457:499 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 5 10 theme iso-Asp 679:685 arg1 formation 666:674 the formation 662:674 the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate 662:746 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 2 11 theme Asn 290:292 arg1 residues 294:301 glycosylated Asn residues 277:301 glycosylated Asn residues 277:301 PNGase F deglycosylation converts glycosylated Asn residues into Asp. 36756538 6 12 link N-linked 853:860 arg1 sites 876:880 N-linked glycosylation sites 853:880 N-linked glycosylation sites 853:880 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 1 13 gly glycosylation 99:111 arg2 glycosylation 99:111 N-linked glycosylation 90:111 N-linked glycosylation 90:111 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 1 13 gly glycosylation 99:111 arg2 sites 81:85 sites 81:85 sites of N-linked glycosylation on a protein 81:124 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 4 14 theme site 488:491 arg1 mapping 493:499 N-glycosylation site mapping 472:499 N-glycosylation site mapping 472:499 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 5 15 theme pH-dependent 625:636 arg1 process 638:644 a pH-dependent process 623:644 a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp 623:850 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 5 15 theme pH-dependent 625:636 arg1 Deamidation 608:618 Deamidation 608:618 Deamidation 608:618 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 2 16 theme glycosylated 277:288 arg1 residues 294:301 glycosylated Asn residues 277:301 glycosylated Asn residues 277:301 PNGase F deglycosylation converts glycosylated Asn residues into Asp. 36756538 1 17 theme sites 168:172 arg1 identification 139:152 the identification 135:152 the identification of deamidated sites 135:172 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 2 18 gly glycosylated 277:288 arg1 residues 294:301 glycosylated Asn residues 277:301 glycosylated Asn residues 277:301 PNGase F deglycosylation converts glycosylated Asn residues into Asp. 36756538 6 19 theme Asn-X-Ser/Thr 1018:1030 arg1 sequence 1009:1016 the consensus sequence Asn-X-Ser/Thr 995:1030 the consensus sequence Asn-X-Ser/Thr 995:1030 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 3 20 theme liquid 372:377 arg1 spectrometry 406:417 liquid chromatography-tandem mass spectrometry 372:417 liquid chromatography-tandem mass spectrometry analysis 372:426 The 1-Da mass tag created by this process is observable by liquid chromatography-tandem mass spectrometry analysis. 36756538 5 21 theme PNGase 757:762 arg1 deglycosylation 766:780 PNGase F deglycosylation 757:780 PNGase F deglycosylation 757:780 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 6 22 theme chromatographic 1071:1085 arg1 peaks 1087:1091 2 chromatographic peaks 1069:1091 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp 1069:1138 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 7 23 from investigators 1178:1190 arg1 field 1199:1203 the field 1195:1203 the field 1195:1203 The intent of this study is to alert investigators in the field to the potential and unexpected errors resulting from this phenomenon and to suggest a strategy to overcome this pitfall and limit the number of false-positive identifications. 36756538 3 24 theme chromatography-tandem 379:399 arg1 spectrometry 406:417 liquid chromatography-tandem mass spectrometry 372:417 liquid chromatography-tandem mass spectrometry analysis 372:426 The 1-Da mass tag created by this process is observable by liquid chromatography-tandem mass spectrometry analysis. 36756538 7 25 theme potential 1212:1220 arg1 errors 1237:1242 the potential and unexpected errors 1208:1242 the potential and unexpected errors resulting from this phenomenon 1208:1273 The intent of this study is to alert investigators in the field to the potential and unexpected errors resulting from this phenomenon and to suggest a strategy to overcome this pitfall and limit the number of false-positive identifications. 36756538 6 26 theme N-linked 853:860 arg1 sites 876:880 N-linked glycosylation sites 853:880 N-linked glycosylation sites 853:880 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 0 27 theme Glycosylation 26:38 arg1 Mapping 45:51 Glycosylation Site Mapping 26:51 Glycosylation Site Mapping 26:51 Reducing Interferences in Glycosylation Site Mapping. 36756538 5 28 theme native 699:704 arg1 Asp 706:708 native Asp 699:708 native Asp (n-Asp) 699:716 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 5 28 theme native 699:704 arg1 n-Asp 711:715 n-Asp 711:715 n-Asp 711:715 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 1 29 theme N-linked 90:97 arg1 glycosylation 99:111 N-linked glycosylation 90:111 N-linked glycosylation 90:111 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 6 30 gly glycosylation 862:874 arg2 sites 876:880 N-linked glycosylation sites 853:880 N-linked glycosylation sites 853:880 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 5 31 theme glycosylation 815:827 arg1 residue 833:839 the glycosylation Asn residue 811:839 the glycosylation Asn residue 811:839 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 5 32 theme Asp 706:708 arg1 formation 666:674 the formation 662:674 the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate 662:746 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 6 33 theme glycosylation 862:874 arg1 sites 876:880 N-linked glycosylation sites 853:880 N-linked glycosylation sites 853:880 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 1 34 theme glycosylation 99:111 arg1 sites 81:85 sites 81:85 sites of N-linked glycosylation on a protein 81:124 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 1 34 theme glycosylation 99:111 arg1 glycosylation 99:111 N-linked glycosylation 90:111 N-linked glycosylation 90:111 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 5 35 theme Asn 829:831 arg1 residue 833:839 the glycosylation Asn residue 811:839 the glycosylation Asn residue 811:839 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 5 36 theme F 764:764 arg1 deglycosylation 766:780 PNGase F deglycosylation 757:780 PNGase F deglycosylation 757:780 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 6 37 theme peak 949:952 arg1 presence 912:919 the presence 908:919 the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr 908:1030 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 5 38 theme residue 833:839 arg1 conversion 797:806 the conversion 793:806 the conversion of the glycosylation Asn residue into n-Asp 793:850 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 7 39 theme false-positive 1350:1363 arg1 identifications 1365:1379 false-positive identifications 1350:1379 false-positive identifications 1350:1379 The intent of this study is to alert investigators in the field to the potential and unexpected errors resulting from this phenomenon and to suggest a strategy to overcome this pitfall and limit the number of false-positive identifications. 36756538 1 40 theme peptide-N-glycosidase 207:227 arg1 F 239:239 PNGase F 232:239 PNGase F 232:239 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 1 40 theme peptide-N-glycosidase 207:227 arg1 F 229:229 peptide-N-glycosidase F 207:229 peptide-N-glycosidase F (PNGase F) 207:240 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 0 41 theme Site 40:43 arg1 Mapping 45:51 Glycosylation Site Mapping 26:51 Glycosylation Site Mapping 26:51 Reducing Interferences in Glycosylation Site Mapping. 36756538 6 42 theme chromatographic 933:947 arg1 peak 949:952 a single chromatographic peak 924:952 a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr 924:1030 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 4 43 theme N-glycosylation 472:486 arg1 site 488:491 N-glycosylation site 472:491 N-glycosylation site mapping 472:499 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 7 44 theme identifications 1365:1379 arg1 number 1340:1345 the number 1336:1345 the number of false-positive identifications 1336:1379 The intent of this study is to alert investigators in the field to the potential and unexpected errors resulting from this phenomenon and to suggest a strategy to overcome this pitfall and limit the number of false-positive identifications. 36756538 5 45 theme succinimide 723:733 arg1 intermediate 735:746 a succinimide intermediate 721:746 a succinimide intermediate 721:746 Deamidation is a pH-dependent process that results in the formation of iso-Asp (i-Asp) and native Asp (n-Asp) by a succinimide intermediate, whereas PNGase F deglycosylation results in the conversion of the glycosylation Asn residue into n-Asp. 36756538 3 46 theme mass 401:404 arg1 spectrometry 406:417 liquid chromatography-tandem mass spectrometry 372:417 liquid chromatography-tandem mass spectrometry analysis 372:426 The 1-Da mass tag created by this process is observable by liquid chromatography-tandem mass spectrometry analysis. 36756538 4 47 theme residues 536:543 arg1 interference 441:452 A potential interference 429:452 A potential interference to this method of N-glycosylation site mapping 429:499 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 4 47 theme residues 536:543 arg1 deamidation 517:527 the chemical deamidation 504:527 the chemical deamidation 504:527 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 3 48 theme spectrometry 406:417 arg1 analysis 419:426 liquid chromatography-tandem mass spectrometry analysis 372:426 liquid chromatography-tandem mass spectrometry analysis 372:426 The 1-Da mass tag created by this process is observable by liquid chromatography-tandem mass spectrometry analysis. 36756538 4 49 theme potential 431:439 arg1 interference 441:452 A potential interference 429:452 A potential interference to this method of N-glycosylation site mapping 429:499 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 4 49 theme potential 431:439 arg1 deamidation 517:527 the chemical deamidation 504:527 the chemical deamidation 504:527 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 6 50 theme n-Asp 1124:1128 arg1 presence 1112:1119 the presence 1108:1119 the presence of n-Asp and i-Asp 1108:1138 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 2 51 theme F 250:250 arg1 deglycosylation 252:266 PNGase F deglycosylation 243:266 PNGase F deglycosylation 243:266 PNGase F deglycosylation converts glycosylated Asn residues into Asp. 36756538 1 52 dep method 64:69 arg1 locate 74:79 locate 74:79 to locate sites of N-linked glycosylation on a protein 71:124 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 1 53 from sites 81:85 arg1 protein 118:124 a protein 116:124 a protein 116:124 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 1 54 theme PNGase 232:237 arg1 F 239:239 PNGase F 232:239 PNGase F 232:239 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 1 54 theme PNGase 232:237 arg1 F 229:229 peptide-N-glycosidase F 207:229 peptide-N-glycosidase F (PNGase F) 207:240 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 1 55 link N-linked 90:97 arg1 glycosylation 99:111 N-linked glycosylation 90:111 N-linked glycosylation 90:111 A current method to locate sites of N-linked glycosylation on a protein involves the identification of deamidated sites after releasing the glycans with peptide-N-glycosidase F (PNGase F). 36756538 2 56 theme PNGase 243:248 arg1 deglycosylation 252:266 PNGase F deglycosylation 243:266 PNGase F deglycosylation 243:266 PNGase F deglycosylation converts glycosylated Asn residues into Asp. 36756538 6 57 theme deamidation 1050:1060 arg1 deamidation 1050:1060 deamidation 1050:1060 deamidation 1050:1060 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 6 57 theme deamidation 1050:1060 arg1 sites 1041:1045 sites 1041:1045 sites of deamidation 1041:1060 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 7 58 theme unexpected 1226:1235 arg1 errors 1237:1242 the potential and unexpected errors 1208:1242 the potential and unexpected errors resulting from this phenomenon 1208:1273 The intent of this study is to alert investigators in the field to the potential and unexpected errors resulting from this phenomenon and to suggest a strategy to overcome this pitfall and limit the number of false-positive identifications. 36756538 4 59 gly N-glycosylation 472:486 arg2 site 488:491 N-glycosylation site 472:491 N-glycosylation site mapping 472:499 A potential interference to this method of N-glycosylation site mapping is the chemical deamidation of Asn residues, which occurs spontaneously and can result in false positives. 36756538 7 60 theme study 1160:1164 arg1 intent 1145:1150 The intent 1141:1150 The intent of this study 1141:1164 The intent of this study is to alert investigators in the field to the potential and unexpected errors resulting from this phenomenon and to suggest a strategy to overcome this pitfall and limit the number of false-positive identifications. 36756538 6 61 theme single 926:931 arg1 peak 949:952 a single chromatographic peak 924:952 a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr 924:1030 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 36756538 6 62 theme consensus 999:1007 arg1 sequence 1009:1016 the consensus sequence Asn-X-Ser/Thr 995:1030 the consensus sequence Asn-X-Ser/Thr 995:1030 N-linked glycosylation sites can thus be identified by the presence of a single chromatographic peak corresponding to an n-Asp residue within the consensus sequence Asn-X-Ser/Thr, whereas sites of deamidation led to 2 chromatographic peaks resulting from the presence of n-Asp and i-Asp. 37329881 1 0 theme immune 170:175 arg1 recognition 177:187 immune recognition 170:187 immune recognition 170:187 Glycosylation of eukaryotic virus particles is common and influences their uptake, trafficking, and immune recognition. 37329881 4 1 link O-linked 559:566 arg1 glycans 568:574 These O-linked glycans 553:574 These O-linked glycans 553:574 These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. 37329881 3 2 attach attached 484:491 arg2 glycans 476:482 glycans 476:482 glycans attached to the C terminus of capsid and tail tube protein subunits 476:550 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 3 2 attach attached 484:491 arg1 terminus 502:509 the C terminus 496:509 the C terminus of capsid and tail tube protein subunits 496:550 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 3 3 theme capsid 514:519 arg1 terminus 502:509 the C terminus 496:509 the C terminus of capsid and tail tube protein subunits 496:550 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 4 4 theme antibody 586:593 arg1 production 595:604 antibody production 586:604 antibody production 586:604 These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. 37329881 6 5 theme little 978:983 arg1 evidence 985:992 little evidence 978:992 little evidence of glycosylation among the broader phage population 978:1044 Putative glycosyltransferases are also encoded by some Gordonia and Streptomyces phages, but there is little evidence of glycosylation among the broader phage population. 37329881 7 6 theme infections 1200:1209 arg1 therapy 1175:1181 phage therapy 1169:1181 phage therapy of Mycobacterium infections 1169:1209 The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections. 37329881 7 7 theme immune 1051:1056 arg1 response 1058:1065 The immune response 1047:1065 The immune response to glycosylated phage virions in mice 1047:1103 The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections. 37329881 4 8 dep influence 576:584 arg1 shielding 623:631 shielding 623:631 shielding viral particles from antibody binding 623:669 These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. 37329881 4 8 dep influence 576:584 arg1 reducing 675:682 reducing 675:682 reducing production of neutralizing antibodies 675:720 These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. 37329881 6 9 theme Putative 876:883 arg1 glycosyltransferases 885:904 Putative glycosyltransferases 876:904 Putative glycosyltransferases 876:904 Putative glycosyltransferases are also encoded by some Gordonia and Streptomyces phages, but there is little evidence of glycosylation among the broader phage population. 37329881 1 10 theme eukaryotic 87:96 arg1 particles 104:112 eukaryotic virus particles 87:112 eukaryotic virus particles 87:112 Glycosylation of eukaryotic virus particles is common and influences their uptake, trafficking, and immune recognition. 37329881 5 11 theme genomic 792:798 arg1 analysis 800:807 genomic analysis 792:807 genomic analysis 792:807 Glycosylation is mediated by phage-encoded glycosyltransferases, and genomic analysis suggests that they are relatively common among mycobacteriophages. 37329881 1 12 theme virus 98:102 arg1 particles 104:112 eukaryotic virus particles 87:112 eukaryotic virus particles 87:112 Glycosylation of eukaryotic virus particles is common and influences their uptake, trafficking, and immune recognition. 37329881 3 13 theme Mycobacteria 445:456 arg1 phages 435:440 several genomically distinct phages 406:440 several genomically distinct phages of Mycobacteria 406:456 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 7 14 theme Mycobacterium 1186:1198 arg1 infections 1200:1209 Mycobacterium infections 1186:1209 Mycobacterium infections 1186:1209 The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections. 37329881 1 15 theme particles 104:112 arg1 Glycosylation 70:82 Glycosylation 70:82 Glycosylation of eukaryotic virus particles 70:112 Glycosylation of eukaryotic virus particles is common and influences their uptake, trafficking, and immune recognition. 37329881 7 16 theme phage 1169:1173 arg1 therapy 1175:1181 phage therapy 1169:1181 phage therapy of Mycobacterium infections 1169:1209 The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections. 37329881 4 17 theme neutralizing 698:709 arg1 antibodies 711:720 neutralizing antibodies 698:720 neutralizing antibodies 698:720 These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. 37329881 0 18 theme Virion 0:5 arg1 glycosylation 7:19 Virion glycosylation 0:19 Virion glycosylation 0:19 Virion glycosylation influences mycobacteriophage immune recognition. 37329881 4 19 theme O-linked 559:566 arg1 glycans 568:574 These O-linked glycans 553:574 These O-linked glycans 553:574 These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. 37329881 7 20 theme advantageous 1143:1154 arg1 property 1156:1163 an advantageous property 1140:1163 an advantageous property for phage therapy of Mycobacterium infections 1140:1209 The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections. 37329881 7 20 theme advantageous 1143:1154 arg1 glycosylation 1119:1131 glycosylation 1119:1131 glycosylation 1119:1131 The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections. 37329881 3 21 dep capsid 514:519 arg1 subunits 543:550 tube protein subunits 530:550 tube protein subunits 530:550 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 0 22 theme mycobacteriophage 32:48 arg1 recognition 57:67 mycobacteriophage immune recognition 32:67 mycobacteriophage immune recognition 32:67 Virion glycosylation influences mycobacteriophage immune recognition. 37329881 7 23 gly glycosylated 1070:1081 arg1 virions 1089:1095 glycosylated phage virions 1070:1095 glycosylated phage virions 1070:1095 The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections. 37329881 4 24 from binding 663:669 arg1 particles 639:647 viral particles 633:647 viral particles from antibody binding 633:669 These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. 37329881 4 25 theme antibody 654:661 arg1 binding 663:669 antibody binding 654:669 antibody binding 654:669 These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. 37329881 3 26 theme tube 530:533 arg1 subunits 543:550 tube protein subunits 530:550 tube protein subunits 530:550 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 7 27 from response 1058:1065 arg1 mice 1100:1103 mice 1100:1103 mice 1100:1103 The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections. 37329881 5 28 theme phage-encoded 752:764 arg1 glycosyltransferases 766:785 phage-encoded glycosyltransferases 752:785 phage-encoded glycosyltransferases 752:785 Glycosylation is mediated by phage-encoded glycosyltransferases, and genomic analysis suggests that they are relatively common among mycobacteriophages. 37329881 6 29 theme Streptomyces 944:955 arg1 phages 957:962 some Gordonia and Streptomyces phages 926:962 phages 957:962 Putative glycosyltransferases are also encoded by some Gordonia and Streptomyces phages, but there is little evidence of glycosylation among the broader phage population. 37329881 0 30 theme immune 50:55 arg1 recognition 57:67 mycobacteriophage immune recognition 32:67 mycobacteriophage immune recognition 32:67 Virion glycosylation influences mycobacteriophage immune recognition. 37329881 6 31 theme phage 1029:1033 arg1 population 1035:1044 the broader phage population 1017:1044 the broader phage population 1017:1044 Putative glycosyltransferases are also encoded by some Gordonia and Streptomyces phages, but there is little evidence of glycosylation among the broader phage population. 37329881 3 32 theme distinct 426:433 arg1 phages 435:440 several genomically distinct phages 406:440 several genomically distinct phages of Mycobacteria 406:456 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 1 33 gly Glycosylation 70:82 arg1 particles 104:112 eukaryotic virus particles 87:112 eukaryotic virus particles 87:112 Glycosylation of eukaryotic virus particles is common and influences their uptake, trafficking, and immune recognition. 37329881 6 34 theme broader 1021:1027 arg1 population 1035:1044 the broader phage population 1017:1044 the broader phage population 1017:1044 Putative glycosyltransferases are also encoded by some Gordonia and Streptomyces phages, but there is little evidence of glycosylation among the broader phage population. 37329881 6 35 theme Gordonia 931:938 arg1 phages 957:962 some Gordonia and Streptomyces phages 926:962 phages 957:962 Putative glycosyltransferases are also encoded by some Gordonia and Streptomyces phages, but there is little evidence of glycosylation among the broader phage population. 37329881 3 36 theme C 500:500 arg1 terminus 502:509 the C terminus 496:509 the C terminus of capsid and tail tube protein subunits 496:550 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 3 37 theme several 406:412 arg1 phages 435:440 several genomically distinct phages 406:440 several genomically distinct phages of Mycobacteria 406:456 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 2 38 theme particles 234:242 arg1 glycosylation 203:215 glycosylation 203:215 glycosylation of bacteriophage particles 203:242 In contrast, glycosylation of bacteriophage particles has not been reported; phage virions typically do not enter the cytoplasm upon infection, and they do not generally inhabit eukaryotic systems. 37329881 3 39 mod modified 462:469 arg1 phages 435:440 several genomically distinct phages 406:440 several genomically distinct phages of Mycobacteria 406:456 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 3 39 mod modified 462:469 arg3 glycans 476:482 glycans 476:482 glycans attached to the C terminus of capsid and tail tube protein subunits 476:550 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 2 40 theme bacteriophage 220:232 arg1 particles 234:242 bacteriophage particles 220:242 bacteriophage particles 220:242 In contrast, glycosylation of bacteriophage particles has not been reported; phage virions typically do not enter the cytoplasm upon infection, and they do not generally inhabit eukaryotic systems. 37329881 4 41 theme antibodies 711:720 arg1 production 684:693 production 684:693 production of neutralizing antibodies 684:720 These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. 37329881 3 42 theme protein 535:541 arg1 subunits 543:550 tube protein subunits 530:550 tube protein subunits 530:550 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 7 43 theme glycosylated 1070:1081 arg1 virions 1089:1095 glycosylated phage virions 1070:1095 glycosylated phage virions 1070:1095 The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections. 37329881 3 44 theme tail 525:528 arg1 terminus 502:509 the C terminus 496:509 the C terminus of capsid and tail tube protein subunits 496:550 We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. 37329881 2 45 gly glycosylation 203:215 arg1 contrast 193:200 contrast 193:200 contrast 193:200 In contrast, glycosylation of bacteriophage particles has not been reported; phage virions typically do not enter the cytoplasm upon infection, and they do not generally inhabit eukaryotic systems. 37329881 2 45 gly glycosylation 203:215 arg1 particles 234:242 bacteriophage particles 220:242 bacteriophage particles 220:242 In contrast, glycosylation of bacteriophage particles has not been reported; phage virions typically do not enter the cytoplasm upon infection, and they do not generally inhabit eukaryotic systems. 37329881 2 46 theme phage 267:271 arg1 virions 273:279 phage virions 267:279 phage virions 267:279 In contrast, glycosylation of bacteriophage particles has not been reported; phage virions typically do not enter the cytoplasm upon infection, and they do not generally inhabit eukaryotic systems. 37329881 7 47 theme phage 1083:1087 arg1 virions 1089:1095 glycosylated phage virions 1070:1095 glycosylated phage virions 1070:1095 The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections. 37329881 6 48 theme glycosylation 997:1009 arg1 evidence 985:992 little evidence 978:992 little evidence of glycosylation among the broader phage population 978:1044 Putative glycosyltransferases are also encoded by some Gordonia and Streptomyces phages, but there is little evidence of glycosylation among the broader phage population. 37329881 2 49 theme eukaryotic 368:377 arg1 systems 379:385 eukaryotic systems 368:385 eukaryotic systems 368:385 In contrast, glycosylation of bacteriophage particles has not been reported; phage virions typically do not enter the cytoplasm upon infection, and they do not generally inhabit eukaryotic systems. 37329881 4 50 theme viral 633:637 arg1 particles 639:647 viral particles 633:647 viral particles from antibody binding 633:669 These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. 35563467 6 0 dep blot 936:939 arg1 analyses 960:967 analyses 960:967 analyses of cerebellar extracts 960:990 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 7 1 theme calbindin 1195:1203 arg1 staining 1205:1212 reduced calbindin staining 1187:1212 reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice 1187:1256 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 4 2 from MGAT5 700:704 arg1 deficient 687:695 deficient 687:695 deficient 687:695 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 6 3 theme Western 928:934 arg1 blot 936:939 Western blot 928:939 Western blot 928:939 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 9 4 theme MGAT5 1754:1758 arg1 SNPs 1760:1763 two MGAT5 SNPs 1750:1763 two MGAT5 SNPs associated with multiple sclerosis 1750:1798 To examine this with respect to MGAT5, we analyzed 111 NPC1 patients for two MGAT5 SNPs associated with multiple sclerosis; however, we did not identify an association with NPC1 phenotypic severity. 35563467 4 5 theme complex 595:601 arg1 glycosylation 621:633 complex asparagine-linked glycosylation 595:633 complex asparagine-linked glycosylation 595:633 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 3 6 theme neuron 556:561 arg1 loss 563:566 cerebellar Purkinje neuron loss 536:566 cerebellar Purkinje neuron loss 536:566 This LAMP1 form was found on activated microglia, and its appearance correlated both spatially and temporally with cerebellar Purkinje neuron loss. 35563467 4 7 from deficient 687:695 arg1 MGAT5 700:704 MGAT5 700:704 MGAT5 700:704 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 4 7 from deficient 687:695 arg1 transferase 737:747 a key Golgi-resident glycosyl transferase 707:747 a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation 707:799 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 4 8 theme knock-out 672:680 arg1 mice 682:685 NPC1 knock-out mice 667:685 NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation 667:799 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 7 9 theme cerebellar 1154:1163 arg1 extracts 1165:1172 cerebellar extracts 1154:1172 cerebellar extracts 1154:1172 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 3 10 theme cerebellar 536:545 arg1 loss 563:566 cerebellar Purkinje neuron loss 536:566 cerebellar Purkinje neuron loss 536:566 This LAMP1 form was found on activated microglia, and its appearance correlated both spatially and temporally with cerebellar Purkinje neuron loss. 35563467 5 11 theme NPC1 887:890 arg1 onset 900:904 earlier NPC1 disease onset 879:904 earlier NPC1 disease onset 879:904 Our results show that Mgat5 mice were smaller than Mgat5 mice, and exhibited earlier NPC1 disease onset and reduced lifespan. 35563467 9 12 theme multiple 1781:1788 arg1 sclerosis 1790:1798 multiple sclerosis 1781:1798 multiple sclerosis 1781:1798 To examine this with respect to MGAT5, we analyzed 111 NPC1 patients for two MGAT5 SNPs associated with multiple sclerosis; however, we did not identify an association with NPC1 phenotypic severity. 35563467 4 13 theme deficient 687:695 arg1 mice 682:685 NPC1 knock-out mice 667:685 NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation 667:799 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 2 14 theme glycosylated 321:332 arg1 form 334:337 a complex asparagine-linked glycosylated form 293:337 a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) 293:387 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 8 15 link asparagine-linked 1435:1451 arg1 glycosylation 1453:1465 reduced asparagine-linked glycosylation 1427:1465 reduced asparagine-linked glycosylation 1427:1465 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 7 16 theme Western 1129:1135 arg1 analysis 1142:1149 Western blot analysis 1129:1149 Western blot analysis of cerebellar extracts 1129:1172 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 6 17 link asparagine-linked 1027:1043 arg1 glycosylation 1045:1057 complex asparagine-linked glycosylation 1019:1057 complex asparagine-linked glycosylation 1019:1057 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 1 18 theme protein 206:212 arg1 stability 214:222 protein stability 206:222 protein stability 206:222 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 6 19 theme extracts 983:990 arg1 analyses 960:967 analyses 960:967 analyses of cerebellar extracts 960:990 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 2 20 link asparagine-linked 303:319 arg1 form 334:337 a complex asparagine-linked glycosylated form 293:337 a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) 293:387 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 4 21 theme Golgi-resident 713:726 arg1 MGAT5 700:704 MGAT5 700:704 MGAT5 700:704 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 4 21 theme Golgi-resident 713:726 arg1 transferase 737:747 a key Golgi-resident glycosyl transferase 707:747 a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation 707:799 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 2 22 from appearance 279:288 arg1 cerebellum 396:405 the cerebellum 392:405 the cerebellum of Npc1 mice 392:418 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 1 23 theme key 143:145 arg1 roles 147:151 key roles 143:151 key roles 143:151 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 8 24 theme asparagine-linked 1572:1588 arg1 glycosylation 1590:1602 asparagine-linked glycosylation 1572:1602 asparagine-linked glycosylation 1572:1602 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 7 25 theme Mgat5 1390:1394 arg1 mice 1396:1399 Mgat5 mice 1390:1399 Mgat5 mice 1390:1399 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 7 26 theme sections 1304:1311 arg1 staining 1281:1288 immunofluorescent staining 1263:1288 immunofluorescent staining of cerebellar sections 1263:1311 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 9 27 theme NPC1 1850:1853 arg1 severity 1866:1873 NPC1 phenotypic severity 1850:1873 NPC1 phenotypic severity 1850:1873 To examine this with respect to MGAT5, we analyzed 111 NPC1 patients for two MGAT5 SNPs associated with multiple sclerosis; however, we did not identify an association with NPC1 phenotypic severity. 35563467 6 28 theme asparagine-linked 1027:1043 arg1 glycosylation 1045:1057 complex asparagine-linked glycosylation 1019:1057 complex asparagine-linked glycosylation 1019:1057 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 6 29 from absence 1068:1074 arg1 glycosylation 1045:1057 complex asparagine-linked glycosylation 1019:1057 complex asparagine-linked glycosylation 1019:1057 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 8 30 theme reduced 1427:1433 arg1 glycosylation 1453:1465 reduced asparagine-linked glycosylation 1427:1465 reduced asparagine-linked glycosylation 1427:1465 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 8 31 theme disease 1482:1488 arg1 severity 1490:1497 NPC1 disease severity 1477:1497 NPC1 disease severity in mice 1477:1505 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 0 32 theme C1 83:84 arg1 Pathology 86:94 Type C1 Pathology 78:94 Type C1 Pathology 78:94 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 0 32 theme C1 83:84 arg1 Modifier 44:51 A Potential Modifier 32:51 A Potential Modifier of Niemann-Pick Disease 32:75 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 8 33 theme severity 1630:1637 arg1 progression 1639:1649 disease severity progression 1622:1649 disease severity progression in individuals with NPC1 1622:1674 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 8 34 link asparagine-linked 1572:1588 arg1 glycosylation 1590:1602 asparagine-linked glycosylation 1572:1602 asparagine-linked glycosylation 1572:1602 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 0 35 theme Potential 34:42 arg1 Pathology 86:94 Type C1 Pathology 78:94 Type C1 Pathology 78:94 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 0 35 theme Potential 34:42 arg1 Modifier 44:51 A Potential Modifier 32:51 A Potential Modifier of Niemann-Pick Disease 32:75 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 3 36 located found 441:445 arg1 microglia 460:468 activated microglia 450:468 activated microglia 450:468 This LAMP1 form was found on activated microglia, and its appearance correlated both spatially and temporally with cerebellar Purkinje neuron loss. 35563467 3 36 located found 441:445 arg2 form 432:435 This LAMP1 form 421:435 This LAMP1 form 421:435 This LAMP1 form was found on activated microglia, and its appearance correlated both spatially and temporally with cerebellar Purkinje neuron loss. 35563467 7 37 theme cerebellar 1293:1302 arg1 sections 1304:1311 cerebellar sections 1293:1311 cerebellar sections 1293:1311 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 8 38 theme NPC1 1477:1480 arg1 severity 1490:1497 NPC1 disease severity 1477:1497 NPC1 disease severity in mice 1477:1505 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 3 39 theme LAMP1 426:430 arg1 form 432:435 This LAMP1 form 421:435 This LAMP1 form 421:435 This LAMP1 form was found on activated microglia, and its appearance correlated both spatially and temporally with cerebellar Purkinje neuron loss. 35563467 0 40 theme Complex 0:6 arg1 Glycosylation 17:29 Complex N-Linked Glycosylation 0:29 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 0:95 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 6 41 gly hyper-glycosylated 1083:1100 arg1 LAMP1 1102:1106 the hyper-glycosylated LAMP1 1079:1106 the hyper-glycosylated LAMP1 previously observed 1079:1126 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 4 42 theme asparagine-linked 769:785 arg1 glycosylation 787:799 complex asparagine-linked glycosylation 761:799 complex asparagine-linked glycosylation 761:799 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 8 43 with individuals 1654:1664 arg1 NPC1 1671:1674 NPC1 1671:1674 NPC1 1671:1674 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 5 44 theme Mgat5 853:857 arg1 mice 859:862 Mgat5 mice 853:862 Mgat5 mice 853:862 Our results show that Mgat5 mice were smaller than Mgat5 mice, and exhibited earlier NPC1 disease onset and reduced lifespan. 35563467 1 45 theme Complex 97:103 arg1 glycosylation 123:135 Complex asparagine-linked glycosylation 97:135 Complex asparagine-linked glycosylation 97:135 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 6 46 theme hyper-glycosylated 1083:1100 arg1 LAMP1 1102:1106 the hyper-glycosylated LAMP1 1079:1106 the hyper-glycosylated LAMP1 previously observed 1079:1126 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 6 47 from reduction 1006:1014 arg1 glycosylation 1045:1057 complex asparagine-linked glycosylation 1019:1057 complex asparagine-linked glycosylation 1019:1057 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 7 48 theme mutant 1246:1251 arg1 mice 1253:1256 Mgat5 mutant mice 1240:1256 Mgat5 mutant mice 1240:1256 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 2 49 theme mice 415:418 arg1 cerebellum 396:405 the cerebellum 392:405 the cerebellum of Npc1 mice 392:418 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 7 50 from astrogliosis 1374:1385 arg1 mice 1396:1399 Mgat5 mice 1390:1399 Mgat5 mice 1390:1399 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 0 51 theme Niemann-Pick 56:67 arg1 Disease 69:75 Niemann-Pick Disease 56:75 Niemann-Pick Disease 56:75 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 2 52 theme protein 371:377 arg1 form 334:337 a complex asparagine-linked glycosylated form 293:337 a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) 293:387 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 7 53 theme increased 1364:1372 arg1 astrogliosis 1374:1385 increased astrogliosis 1364:1385 increased astrogliosis in Mgat5 mice 1364:1399 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 1 54 link asparagine-linked 105:121 arg1 glycosylation 123:135 Complex asparagine-linked glycosylation 97:135 Complex asparagine-linked glycosylation 97:135 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 2 55 theme lysosome-associated 342:360 arg1 protein 371:377 lysosome-associated membrane protein 1 342:379 lysosome-associated membrane protein 1 (LAMP1) 342:387 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 2 55 theme lysosome-associated 342:360 arg1 LAMP1 382:386 LAMP1 382:386 LAMP1 382:386 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 0 56 dep Glycosylation 17:29 arg1 Pathology 86:94 Type C1 Pathology 78:94 Type C1 Pathology 78:94 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 0 56 dep Glycosylation 17:29 arg1 Modifier 44:51 A Potential Modifier 32:51 A Potential Modifier of Niemann-Pick Disease 32:75 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 7 57 theme neurons 1352:1358 arg1 levels 1333:1338 decreased levels 1323:1338 decreased levels of Purkinje neurons 1323:1358 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 7 57 theme neurons 1352:1358 arg1 astrogliosis 1374:1385 increased astrogliosis 1364:1385 increased astrogliosis in Mgat5 mice 1364:1399 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 4 58 theme asparagine-linked 603:619 arg1 glycosylation 621:633 complex asparagine-linked glycosylation 595:633 complex asparagine-linked glycosylation 595:633 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 2 59 gly glycosylated 321:332 arg1 protein 371:377 lysosome-associated membrane protein 1 342:379 lysosome-associated membrane protein 1 (LAMP1) 342:387 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 2 59 gly glycosylated 321:332 arg1 LAMP1 382:386 LAMP1 382:386 LAMP1 382:386 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 2 59 gly glycosylated 321:332 arg1 form 334:337 a complex asparagine-linked glycosylated form 293:337 a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) 293:387 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 3 60 theme activated 450:458 arg1 microglia 460:468 activated microglia 450:468 activated microglia 450:468 This LAMP1 form was found on activated microglia, and its appearance correlated both spatially and temporally with cerebellar Purkinje neuron loss. 35563467 8 61 from progression 1639:1649 arg1 individuals 1654:1664 individuals 1654:1664 individuals with NPC1 1654:1674 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 6 62 theme lectin 945:950 arg1 binding 952:958 lectin binding 945:958 lectin binding 945:958 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 8 63 from mutations 1541:1549 arg1 genes 1554:1558 genes 1554:1558 genes involved in asparagine-linked glycosylation 1554:1602 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 7 64 theme reduced 1187:1193 arg1 staining 1205:1212 reduced calbindin staining 1187:1212 reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice 1187:1256 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 7 65 theme decreased 1323:1331 arg1 levels 1333:1338 decreased levels 1323:1338 decreased levels of Purkinje neurons 1323:1358 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 7 66 theme extracts 1165:1172 arg1 analysis 1142:1149 Western blot analysis 1129:1149 Western blot analysis of cerebellar extracts 1129:1172 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 3 67 theme Purkinje 547:554 arg1 loss 563:566 cerebellar Purkinje neuron loss 536:566 cerebellar Purkinje neuron loss 536:566 This LAMP1 form was found on activated microglia, and its appearance correlated both spatially and temporally with cerebellar Purkinje neuron loss. 35563467 7 68 from levels 1333:1338 arg1 mice 1396:1399 Mgat5 mice 1390:1399 Mgat5 mice 1390:1399 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 5 69 theme disease 892:898 arg1 onset 900:904 earlier NPC1 disease onset 879:904 earlier NPC1 disease onset 879:904 Our results show that Mgat5 mice were smaller than Mgat5 mice, and exhibited earlier NPC1 disease onset and reduced lifespan. 35563467 5 70 theme earlier 879:885 arg1 onset 900:904 earlier NPC1 disease onset 879:904 earlier NPC1 disease onset 879:904 Our results show that Mgat5 mice were smaller than Mgat5 mice, and exhibited earlier NPC1 disease onset and reduced lifespan. 35563467 4 71 theme NPC1 667:670 arg1 mice 682:685 NPC1 knock-out mice 667:685 NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation 667:799 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 7 72 theme blot 1137:1140 arg1 analysis 1142:1149 Western blot analysis 1129:1149 Western blot analysis of cerebellar extracts 1129:1172 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 2 73 theme form 334:337 arg1 appearance 279:288 the appearance 275:288 the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice 275:418 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 1 74 theme cellular 186:193 arg1 signaling 195:203 cellular signaling 186:203 cellular signaling 186:203 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 2 75 theme asparagine-linked 303:319 arg1 form 334:337 a complex asparagine-linked glycosylated form 293:337 a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) 293:387 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 6 76 theme cerebellar 972:981 arg1 extracts 983:990 cerebellar extracts 972:990 cerebellar extracts 972:990 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 1 77 theme asparagine-linked 105:121 arg1 glycosylation 123:135 Complex asparagine-linked glycosylation 97:135 Complex asparagine-linked glycosylation 97:135 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 4 78 theme key 709:711 arg1 MGAT5 700:704 MGAT5 700:704 MGAT5 700:704 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 4 78 theme key 709:711 arg1 transferase 737:747 a key Golgi-resident glycosyl transferase 707:747 a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation 707:799 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 4 79 theme glycosyl 728:735 arg1 MGAT5 700:704 MGAT5 700:704 MGAT5 700:704 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 4 79 theme glycosyl 728:735 arg1 transferase 737:747 a key Golgi-resident glycosyl transferase 707:747 a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation 707:799 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 0 80 theme Disease 69:75 arg1 Pathology 86:94 Type C1 Pathology 78:94 Type C1 Pathology 78:94 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 0 80 theme Disease 69:75 arg1 Modifier 44:51 A Potential Modifier 32:51 A Potential Modifier of Niemann-Pick Disease 32:75 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 9 81 with association 1833:1843 arg1 severity 1866:1873 NPC1 phenotypic severity 1850:1873 NPC1 phenotypic severity 1850:1873 To examine this with respect to MGAT5, we analyzed 111 NPC1 patients for two MGAT5 SNPs associated with multiple sclerosis; however, we did not identify an association with NPC1 phenotypic severity. 35563467 7 82 from staining 1205:1212 arg1 mice 1223:1226 Mgat5 mice 1217:1226 Mgat5 mice compared to Mgat5 mutant mice 1217:1256 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 7 83 theme immunofluorescent 1263:1279 arg1 staining 1281:1288 immunofluorescent staining 1263:1288 immunofluorescent staining of cerebellar sections 1263:1311 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 0 84 theme Type 78:81 arg1 Pathology 86:94 Type C1 Pathology 78:94 Type C1 Pathology 78:94 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 0 84 theme Type 78:81 arg1 Modifier 44:51 A Potential Modifier 32:51 A Potential Modifier of Niemann-Pick Disease 32:75 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 1 85 theme cellular 156:163 arg1 response 236:243 immune response 229:243 immune response 229:243 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 1 85 theme cellular 156:163 arg1 signaling 195:203 cellular signaling 186:203 cellular signaling 186:203 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 1 85 theme cellular 156:163 arg1 stability 214:222 protein stability 206:222 protein stability 206:222 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 1 85 theme cellular 156:163 arg1 functions 165:173 cellular functions 156:173 cellular functions 156:173 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 9 86 theme phenotypic 1855:1864 arg1 severity 1866:1873 NPC1 phenotypic severity 1850:1873 NPC1 phenotypic severity 1850:1873 To examine this with respect to MGAT5, we analyzed 111 NPC1 patients for two MGAT5 SNPs associated with multiple sclerosis; however, we did not identify an association with NPC1 phenotypic severity. 35563467 8 87 theme disease 1622:1628 arg1 progression 1639:1649 disease severity progression 1622:1649 disease severity progression in individuals with NPC1 1622:1674 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 9 88 theme 111 1728:1730 arg1 patients 1737:1744 111 NPC1 patients 1728:1744 111 NPC1 patients 1728:1744 To examine this with respect to MGAT5, we analyzed 111 NPC1 patients for two MGAT5 SNPs associated with multiple sclerosis; however, we did not identify an association with NPC1 phenotypic severity. 35563467 2 89 theme complex 295:301 arg1 form 334:337 a complex asparagine-linked glycosylated form 293:337 a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) 293:387 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 6 90 theme complex 1019:1025 arg1 glycosylation 1045:1057 complex asparagine-linked glycosylation 1019:1057 complex asparagine-linked glycosylation 1019:1057 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 4 91 from importance 581:590 arg1 pathology 643:651 NPC1 pathology 638:651 NPC1 pathology 638:651 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 8 92 theme asparagine-linked 1435:1451 arg1 glycosylation 1453:1465 reduced asparagine-linked glycosylation 1427:1465 reduced asparagine-linked glycosylation 1427:1465 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35563467 0 93 theme N-Linked 8:15 arg1 Glycosylation 17:29 Complex N-Linked Glycosylation 0:29 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 0:95 Complex N-Linked Glycosylation: A Potential Modifier of Niemann-Pick Disease, Type C1 Pathology. 35563467 6 94 theme LAMP1 1102:1106 arg1 absence 1068:1074 the absence 1064:1074 the absence of the hyper-glycosylated LAMP1 previously observed 1064:1126 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 6 94 theme LAMP1 1102:1106 arg1 reduction 1006:1014 the reduction 1002:1014 the reduction in complex asparagine-linked glycosylation 1002:1057 Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. 35563467 4 95 theme complex 761:767 arg1 glycosylation 787:799 complex asparagine-linked glycosylation 761:799 complex asparagine-linked glycosylation 761:799 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 7 96 theme Mgat5 1217:1221 arg1 mice 1223:1226 Mgat5 mice 1217:1226 Mgat5 mice compared to Mgat5 mutant mice 1217:1256 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 2 97 theme Npc1 410:413 arg1 mice 415:418 Npc1 mice 410:418 Npc1 mice 410:418 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 5 98 theme Mgat5 824:828 arg1 mice 830:833 Mgat5 mice 824:833 Mgat5 mice 824:833 Our results show that Mgat5 mice were smaller than Mgat5 mice, and exhibited earlier NPC1 disease onset and reduced lifespan. 35563467 4 99 link asparagine-linked 603:619 arg1 glycosylation 621:633 complex asparagine-linked glycosylation 595:633 complex asparagine-linked glycosylation 595:633 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 2 100 theme membrane 362:369 arg1 protein 371:377 lysosome-associated membrane protein 1 342:379 lysosome-associated membrane protein 1 (LAMP1) 342:387 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 2 100 theme membrane 362:369 arg1 LAMP1 382:386 LAMP1 382:386 LAMP1 382:386 Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1 mice. 35563467 7 101 theme Purkinje 1343:1350 arg1 neurons 1352:1358 Purkinje neurons 1343:1358 Purkinje neurons 1343:1358 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 4 102 theme glycosylation 621:633 arg1 importance 581:590 the importance 577:590 the importance of complex asparagine-linked glycosylation in NPC1 pathology 577:651 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 1 103 theme immune 229:234 arg1 response 236:243 immune response 229:243 immune response 229:243 Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. 35563467 9 104 theme NPC1 1732:1735 arg1 patients 1737:1744 111 NPC1 patients 1728:1744 111 NPC1 patients 1728:1744 To examine this with respect to MGAT5, we analyzed 111 NPC1 patients for two MGAT5 SNPs associated with multiple sclerosis; however, we did not identify an association with NPC1 phenotypic severity. 35563467 4 105 link asparagine-linked 769:785 arg1 glycosylation 787:799 complex asparagine-linked glycosylation 761:799 complex asparagine-linked glycosylation 761:799 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 4 106 theme NPC1 638:641 arg1 pathology 643:651 NPC1 pathology 638:651 NPC1 pathology 638:651 To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. 35563467 7 107 theme Mgat5 1240:1244 arg1 mice 1253:1256 Mgat5 mutant mice 1240:1256 Mgat5 mutant mice 1240:1256 Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5 mice compared to Mgat5 mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5 mice. 35563467 8 108 from severity 1490:1497 arg1 mice 1502:1505 mice 1502:1505 mice 1502:1505 Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. 35459471 4 0 theme complex 637:643 arg1 carbohydrates 645:657 these complex carbohydrates 631:657 these complex carbohydrates 631:657 Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. 35459471 3 1 theme anabolic 556:563 arg1 facets 523:528 Two critical, but understudied, facets 491:528 Two critical, but understudied, facets of glucose metabolism 491:550 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 3 1 theme anabolic 556:563 arg1 pathways 565:572 anabolic pathways 556:572 anabolic pathways for glycogen and N-linked glycan biosynthesis 556:618 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 3 2 theme glycan 600:605 arg1 biosynthesis 607:618 glycogen and N-linked glycan biosynthesis 578:618 glycogen and N-linked glycan biosynthesis 578:618 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 5 3 theme HDRC 875:878 arg1 analysis 881:888 clustering (HDRC) analysis 863:888 clustering (HDRC) analysis 863:888 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 6 4 theme cancer-associated 1319:1335 arg1 fibroblasts 1337:1347 cancer-associated fibroblasts 1319:1347 cancer-associated fibroblasts 1319:1347 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 0 5 theme High-dimensionality 0:18 arg1 clustering 30:39 High-dimensionality reduction clustering 0:39 High-dimensionality reduction clustering of complex carbohydrates 0:64 High-dimensionality reduction clustering of complex carbohydrates to study lung cancer metabolic heterogeneity. 35459471 4 6 theme cell 761:764 arg1 populations 766:776 distinct cell populations 752:776 distinct cell populations within the tumor heterogeneity 752:807 Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. 35459471 6 7 from clusters 1182:1189 arg1 tissues 1157:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 2 8 theme solid 332:336 arg1 tumors 338:343 solid tumors 332:343 solid tumors 332:343 Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. 35459471 9 9 theme promising 1677:1685 arg1 potentials 1687:1696 the promising potentials 1673:1696 the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment 1673:1834 Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment. 35459471 8 10 theme cancer 1617:1622 arg1 disparity 1624:1632 lung cancer disparity 1612:1632 lung cancer disparity 1612:1632 Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. 35459471 4 11 theme functional 725:734 arg1 microanatomy 736:747 functional microanatomy 725:747 functional microanatomy in distinct cell populations within the tumor heterogeneity 725:807 Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. 35459471 6 12 theme tumor 1240:1244 arg1 microenvironment 1246:1261 the tumor microenvironment 1236:1261 the tumor microenvironment 1236:1261 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 5 13 theme tissue 1041:1046 arg1 histopathology 1048:1061 tissue histopathology 1041:1061 tissue histopathology 1041:1061 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 9 14 theme stromal 1784:1790 arg1 signaling 1792:1800 regional-specific stromal signaling 1766:1800 regional-specific stromal signaling 1766:1800 Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment. 35459471 6 15 theme tumor 1151:1155 arg1 tissues 1157:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 6 16 theme necrotic 1354:1361 arg1 regions 1363:1369 necrotic regions 1354:1369 necrotic regions 1354:1369 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 3 17 theme understudied 509:520 arg1 facets 523:528 Two critical, but understudied, facets 491:528 Two critical, but understudied, facets of glucose metabolism 491:550 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 3 17 theme understudied 509:520 arg1 pathways 565:572 anabolic pathways 556:572 anabolic pathways for glycogen and N-linked glycan biosynthesis 556:618 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 5 18 theme clustering 863:872 arg1 analysis 881:888 clustering (HDRC) analysis 863:888 clustering (HDRC) analysis 863:888 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 1 19 theme stromal 178:184 arg1 cells 197:201 stromal and cancer cells 178:201 cells 197:201 The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. 35459471 6 20 theme LUAD 1145:1148 arg1 tissues 1157:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 4 21 theme tumor 789:793 arg1 heterogeneity 795:807 the tumor heterogeneity 785:807 the tumor heterogeneity 785:807 Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. 35459471 0 22 theme metabolic 87:95 arg1 heterogeneity 97:109 lung cancer metabolic heterogeneity 75:109 lung cancer metabolic heterogeneity 75:109 High-dimensionality reduction clustering of complex carbohydrates to study lung cancer metabolic heterogeneity. 35459471 1 23 theme cancer 190:195 arg1 cells 197:201 stromal and cancer cells 178:201 cells 197:201 The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. 35459471 6 24 theme adenocarcinoma 1129:1142 arg1 tissues 1157:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 5 25 gly heterogeneity 1077:1089 arg1 histopathology 1048:1061 tissue histopathology 1041:1061 tissue histopathology 1041:1061 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 7 26 dep pathways 1435:1442 arg1 associated 1448:1457 associated 1448:1457 are associated with each distinct pathological region 1444:1496 In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. 35459471 6 27 theme human 1118:1122 arg1 tissues 1157:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 3 28 link N-linked 591:598 arg1 biosynthesis 607:618 glycogen and N-linked glycan biosynthesis 578:618 glycogen and N-linked glycan biosynthesis 578:618 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 8 29 theme HDRC 1538:1541 arg1 analysis 1543:1550 HDRC analysis 1538:1550 HDRC analysis 1538:1550 Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. 35459471 0 30 theme cancer 80:85 arg1 heterogeneity 97:109 lung cancer metabolic heterogeneity 75:109 lung cancer metabolic heterogeneity 75:109 High-dimensionality reduction clustering of complex carbohydrates to study lung cancer metabolic heterogeneity. 35459471 2 31 theme metabolic 422:430 arg1 perturbations 432:444 unique metabolic perturbations 415:444 unique metabolic perturbations between stromal and immune cell populations 415:488 Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. 35459471 5 32 theme desorption/ionization 917:937 arg1 MALDI-MSI 966:974 MALDI-MSI 966:974 MALDI-MSI 966:974 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 5 32 theme desorption/ionization 917:937 arg1 spectrometry 944:955 matrix-assisted laser desorption/ionization mass spectrometry imaging 895:963 matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) 895:975 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 9 33 theme regional-specific 1766:1782 arg1 signaling 1792:1800 regional-specific stromal signaling 1766:1800 regional-specific stromal signaling 1766:1800 Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment. 35459471 6 34 theme distinct 1191:1198 arg1 regions 1200:1206 distinct regions 1191:1206 distinct regions 1191:1206 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 8 35 theme complex 1561:1567 arg1 metabolism 1582:1591 complex carbohydrate metabolism 1561:1591 complex carbohydrate metabolism 1561:1591 Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. 35459471 2 36 theme cell 473:476 arg1 populations 478:488 stromal and immune cell populations 454:488 stromal and immune cell populations 454:488 Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. 35459471 5 37 theme human 1094:1098 arg1 sections 1105:1112 human FFPE sections 1094:1112 human FFPE sections 1094:1112 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 0 38 theme complex 44:50 arg1 carbohydrates 52:64 complex carbohydrates 44:64 complex carbohydrates 44:64 High-dimensionality reduction clustering of complex carbohydrates to study lung cancer metabolic heterogeneity. 35459471 7 39 theme pathological 1478:1489 arg1 region 1491:1496 each distinct pathological region 1464:1496 each distinct pathological region 1464:1496 In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. 35459471 0 40 theme lung 75:78 arg1 cancer 80:85 lung cancer 75:85 lung cancer metabolic heterogeneity 75:109 High-dimensionality reduction clustering of complex carbohydrates to study lung cancer metabolic heterogeneity. 35459471 3 41 theme glucose 533:539 arg1 metabolism 541:550 glucose metabolism 533:550 glucose metabolism 533:550 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 5 42 theme matrix-assisted 895:909 arg1 MALDI-MSI 966:974 MALDI-MSI 966:974 MALDI-MSI 966:974 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 5 42 theme matrix-assisted 895:909 arg1 spectrometry 944:955 matrix-assisted laser desorption/ionization mass spectrometry imaging 895:963 matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) 895:975 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 2 43 theme spectrometry 358:369 arg1 workflows 371:379 pooled mass spectrometry workflows 346:379 pooled mass spectrometry workflows 346:379 Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. 35459471 8 44 theme lung 1612:1615 arg1 disparity 1624:1632 lung cancer disparity 1612:1632 lung cancer disparity 1612:1632 Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. 35459471 5 45 from heterogeneity 1077:1089 arg1 sections 1105:1112 human FFPE sections 1094:1112 human FFPE sections 1094:1112 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 4 46 theme protein-structure 686:702 arg1 function 704:711 protein-structure function 686:711 protein-structure function 686:711 Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. 35459471 7 47 theme unique 1418:1423 arg1 pathways 1435:1442 unique metabolic pathways 1418:1442 unique metabolic pathways are associated with each distinct pathological region 1418:1496 In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. 35459471 1 48 contain contains 139:146 arg2 population 164:173 a heterogeneous population 148:173 a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression 148:301 The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. 35459471 1 48 contain contains 139:146 arg1 microenvironment 122:137 The tumor microenvironment 112:137 The tumor microenvironment 112:137 The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. 35459471 3 49 theme N-linked 591:598 arg1 biosynthesis 607:618 glycogen and N-linked glycan biosynthesis 578:618 glycogen and N-linked glycan biosynthesis 578:618 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 9 50 theme pixel-based 1709:1719 arg1 analysis 1734:1741 pixel-based carbohydrate analysis 1709:1741 pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment 1709:1834 Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment. 35459471 3 51 theme glycogen 578:585 arg1 biosynthesis 607:618 glycogen and N-linked glycan biosynthesis 578:618 glycogen and N-linked glycan biosynthesis 578:618 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 1 52 theme cells 197:201 arg1 population 164:173 a heterogeneous population 148:173 a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression 148:301 The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. 35459471 7 53 theme pathway 1381:1387 arg1 analyses 1400:1407 In-depth pathway enrichment analyses 1372:1407 In-depth pathway enrichment analyses 1372:1407 In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. 35459471 2 54 theme pooled 346:351 arg1 spectrometry 358:369 pooled mass spectrometry 346:369 pooled mass spectrometry workflows 346:379 Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. 35459471 4 55 from microanatomy 736:747 arg1 populations 766:776 distinct cell populations 752:776 distinct cell populations within the tumor heterogeneity 752:807 Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. 35459471 6 56 theme tumor-infiltrating 1287:1304 arg1 lymphocytes 1306:1316 tumor-infiltrating lymphocytes 1287:1316 tumor-infiltrating lymphocytes 1287:1316 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 4 57 theme distinct 752:759 arg1 populations 766:776 distinct cell populations 752:776 distinct cell populations within the tumor heterogeneity 752:807 Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. 35459471 5 58 theme imaging 957:963 arg1 MALDI-MSI 966:974 MALDI-MSI 966:974 MALDI-MSI 966:974 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 5 58 theme imaging 957:963 arg1 spectrometry 944:955 matrix-assisted laser desorption/ionization mass spectrometry imaging 895:963 matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) 895:975 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 8 59 theme disparity 1624:1632 arg1 study 1603:1607 a case study 1596:1607 a case study of lung cancer disparity 1596:1632 Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. 35459471 9 60 theme carbohydrate 1721:1732 arg1 analysis 1734:1741 pixel-based carbohydrate analysis 1709:1741 pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment 1709:1834 Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment. 35459471 1 61 theme heterogeneous 150:162 arg1 population 164:173 a heterogeneous population 148:173 a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression 148:301 The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. 35459471 9 62 theme analysis 1734:1741 arg1 HDRC 1701:1704 HDRC 1701:1704 HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment 1701:1834 Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment. 35459471 7 63 theme enrichment 1389:1398 arg1 analyses 1400:1407 In-depth pathway enrichment analyses 1372:1407 In-depth pathway enrichment analyses 1372:1407 In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. 35459471 1 64 theme metabolic 218:226 arg1 crosstalk 228:236 metabolic crosstalk 218:236 metabolic crosstalk 218:236 The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. 35459471 9 65 theme HDRC 1701:1704 arg1 potentials 1687:1696 the promising potentials 1673:1696 the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment 1673:1834 Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment. 35459471 7 66 theme In-depth 1372:1379 arg1 analyses 1400:1407 In-depth pathway enrichment analyses 1372:1407 In-depth pathway enrichment analyses 1372:1407 In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. 35459471 5 67 theme comprehensive 1013:1025 arg1 assessment 1027:1036 the comprehensive assessment 1009:1036 the comprehensive assessment of tissue histopathology 1009:1061 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 5 68 from assessment 1027:1036 arg1 sections 1105:1112 human FFPE sections 1094:1112 human FFPE sections 1094:1112 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 5 69 theme FFPE 1100:1103 arg1 sections 1105:1112 human FFPE sections 1094:1112 human FFPE sections 1094:1112 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 6 70 theme lung 1124:1127 arg1 tissues 1157:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 human lung adenocarcinoma (LUAD) tumor tissues 1118:1163 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 5 71 theme high-dimensionality 829:847 arg1 reduction 849:857 high-dimensionality reduction 829:857 high-dimensionality reduction 829:857 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 5 72 theme histopathology 1048:1061 arg1 assessment 1027:1036 the comprehensive assessment 1009:1036 the comprehensive assessment of tissue histopathology 1009:1061 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 5 72 theme histopathology 1048:1061 arg1 heterogeneity 1077:1089 metabolic heterogeneity 1067:1089 metabolic heterogeneity in human FFPE sections 1067:1112 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 6 73 theme cell 1212:1215 arg1 populations 1217:1227 cell populations 1212:1227 cell populations 1212:1227 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 3 74 theme critical 495:502 arg1 facets 523:528 Two critical, but understudied, facets 491:528 Two critical, but understudied, facets of glucose metabolism 491:550 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 3 74 theme critical 495:502 arg1 pathways 565:572 anabolic pathways 556:572 anabolic pathways for glycogen and N-linked glycan biosynthesis 556:618 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 5 75 theme laser 911:915 arg1 MALDI-MSI 966:974 MALDI-MSI 966:974 MALDI-MSI 966:974 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 5 75 theme laser 911:915 arg1 spectrometry 944:955 matrix-assisted laser desorption/ionization mass spectrometry imaging 895:963 matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) 895:975 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 5 76 theme metabolic 1067:1075 arg1 heterogeneity 1077:1089 metabolic heterogeneity 1067:1089 metabolic heterogeneity in human FFPE sections 1067:1112 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 8 77 theme analysis 1543:1550 arg1 potential 1525:1533 the potential 1521:1533 the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity 1521:1632 Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. 35459471 2 78 theme unique 415:420 arg1 perturbations 432:444 unique metabolic perturbations 415:444 unique metabolic perturbations between stromal and immune cell populations 415:488 Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. 35459471 5 79 theme mass 939:942 arg1 MALDI-MSI 966:974 MALDI-MSI 966:974 MALDI-MSI 966:974 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 5 79 theme mass 939:942 arg1 spectrometry 944:955 matrix-assisted laser desorption/ionization mass spectrometry imaging 895:963 matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) 895:975 Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. 35459471 1 80 theme tumor 116:120 arg1 microenvironment 122:137 The tumor microenvironment 112:137 The tumor microenvironment 112:137 The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. 35459471 2 81 theme immune 466:471 arg1 populations 478:488 stromal and immune cell populations 454:488 stromal and immune cell populations 454:488 Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. 35459471 0 82 theme carbohydrates 52:64 arg1 clustering 30:39 High-dimensionality reduction clustering 0:39 High-dimensionality reduction clustering of complex carbohydrates 0:64 High-dimensionality reduction clustering of complex carbohydrates to study lung cancer metabolic heterogeneity. 35459471 7 83 theme distinct 1469:1476 arg1 region 1491:1496 each distinct pathological region 1464:1496 each distinct pathological region 1464:1496 In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. 35459471 8 84 theme carbohydrate 1569:1580 arg1 metabolism 1582:1591 complex carbohydrate metabolism 1561:1591 complex carbohydrate metabolism 1561:1591 Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. 35459471 2 85 theme stromal 454:460 arg1 populations 478:488 stromal and immune cell populations 454:488 stromal and immune cell populations 454:488 Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. 35459471 9 86 theme tumor 1813:1817 arg1 microenvironment 1819:1834 the tumor microenvironment 1809:1834 the tumor microenvironment 1809:1834 Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment. 35459471 6 87 theme tumor 1274:1278 arg1 cells 1280:1284 tumor cells 1274:1284 tumor cells 1274:1284 In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. 35459471 3 88 theme metabolism 541:550 arg1 facets 523:528 Two critical, but understudied, facets 491:528 Two critical, but understudied, facets of glucose metabolism 491:550 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 3 88 theme metabolism 541:550 arg1 pathways 565:572 anabolic pathways 556:572 anabolic pathways for glycogen and N-linked glycan biosynthesis 556:618 Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. 35459471 8 89 theme case 1598:1601 arg1 study 1603:1607 a case study 1596:1607 a case study of lung cancer disparity 1596:1632 Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. 35459471 2 90 theme mass 353:356 arg1 spectrometry 358:369 pooled mass spectrometry 346:369 pooled mass spectrometry workflows 346:379 Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. 35459471 1 91 theme tumor 260:264 arg1 growth 266:271 tumor growth 260:271 tumor growth 260:271 The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. 35459471 7 92 theme metabolic 1425:1433 arg1 pathways 1435:1442 unique metabolic pathways 1418:1442 unique metabolic pathways are associated with each distinct pathological region 1418:1496 In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. 35459471 0 93 theme reduction 20:28 arg1 clustering 30:39 High-dimensionality reduction clustering 0:39 High-dimensionality reduction clustering of complex carbohydrates 0:64 High-dimensionality reduction clustering of complex carbohydrates to study lung cancer metabolic heterogeneity. 35870621 8 0 theme glycosylated 1358:1369 arg1 proteins 1371:1378 glycosylated proteins 1358:1378 glycosylated proteins 1358:1378 Mostly key regulators were identified to be glycoproteins, which confirms that glycosylated proteins played important roles in bovine sperm. 35870621 1 1 theme efficiency 332:341 arg1 decline 304:310 the decline 300:310 the decline of the reproductive efficiency 300:341 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 1 2 theme vital 170:174 arg1 role 176:179 a vital role 168:179 a vital role 168:179 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 2 3 mod modification 362:373 arg3 glycosylation 348:360 The glycosylation modification 344:373 The glycosylation modification of protein 344:384 The glycosylation modification of protein has irreplaceable roles in spermatozoa. 35870621 2 3 mod modification 362:373 arg1 protein 378:384 protein 378:384 protein 378:384 The glycosylation modification of protein has irreplaceable roles in spermatozoa. 35870621 1 4 theme detrimental 250:260 arg1 effect 262:267 a detrimental effect 248:267 a detrimental effect 248:267 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 8 5 gly glycoproteins 1323:1335 arg1 glycoproteins 1323:1335 glycoproteins 1323:1335 glycoproteins 1323:1335 Mostly key regulators were identified to be glycoproteins, which confirms that glycosylated proteins played important roles in bovine sperm. 35870621 7 6 from interaction 1266:1276 arg1 genitalia 1241:1249 female genitalia 1234:1249 female genitalia 1234:1249 The biologic functions of the 115 changed proteins are mainly involved in sperm capacitation, migration in female genitalia, and sperm-egg interaction. 35870621 2 7 theme glycosylation 348:360 arg1 modification 362:373 The glycosylation modification 344:373 The glycosylation modification of protein 344:384 The glycosylation modification of protein has irreplaceable roles in spermatozoa. 35870621 6 8 theme glycosylation 1007:1019 arg1 modification 1021:1032 glycosylation modification 1007:1032 glycosylation modification 1007:1032 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 4 9 theme different 727:735 arg1 DEGPs 771:775 DEGPs 771:775 DEGPs 771:775 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 4 9 theme different 727:735 arg1 proteins 761:768 44 different expression glycosylated proteins 724:768 44 different expression glycosylated proteins (DEGPs) 724:776 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 0 10 theme bovine 115:120 arg1 sperm 122:126 frozen bovine sperm 108:126 frozen bovine sperm 108:126 TMT-based quantitative N-glycoproteomic analysis reveals glycoprotein protection can improve the quality of frozen bovine sperm. 35870621 9 11 gly glycoproteins 1454:1466 arg1 glycoproteins 1454:1466 sperm glycoproteins 1448:1466 sperm glycoproteins 1448:1466 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 3 12 theme -labeled 569:576 arg1 glycoproteome 591:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 3 13 theme tandem 548:553 arg1 glycoproteome 591:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 0 14 theme frozen 108:113 arg1 sperm 122:126 frozen bovine sperm 108:126 frozen bovine sperm 108:126 TMT-based quantitative N-glycoproteomic analysis reveals glycoprotein protection can improve the quality of frozen bovine sperm. 35870621 4 15 theme proteins 622:629 arg1 total 608:612 A total 606:612 A total of 2598 proteins and 492 glycoproteins 606:651 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 5 16 gly glycoproteins 877:889 arg1 glycoproteins 877:889 glycoproteins 877:889 glycoproteins of bovine sperm 877:905 Thirty-three DEPs are glycoproteins, which demonstrates that glycoproteins of bovine sperm were seriously affected by cryopreservation. 35870621 3 17 theme mass 555:558 arg1 glycoproteome 591:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 1 18 theme sperm 272:276 arg1 quality 278:284 sperm quality 272:284 sperm quality 272:284 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 5 19 gly glycoproteins 838:850 arg1 glycoproteins 838:850 glycoproteins 838:850 glycoproteins 838:850 Thirty-three DEPs are glycoproteins, which demonstrates that glycoproteins of bovine sperm were seriously affected by cryopreservation. 35870621 5 19 gly glycoproteins 838:850 arg1 DEPs 829:832 Thirty-three DEPs 816:832 Thirty-three DEPs 816:832 Thirty-three DEPs are glycoproteins, which demonstrates that glycoproteins of bovine sperm were seriously affected by cryopreservation. 35870621 3 20 theme bovine 485:490 arg1 spermatozoa 492:502 bovine spermatozoa 485:502 bovine spermatozoa 485:502 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 2 21 theme irreplaceable 390:402 arg1 roles 404:408 irreplaceable roles 390:408 irreplaceable roles 390:408 The glycosylation modification of protein has irreplaceable roles in spermatozoa. 35870621 0 22 theme sperm 122:126 arg1 quality 97:103 the quality 93:103 the quality of frozen bovine sperm 93:126 TMT-based quantitative N-glycoproteomic analysis reveals glycoprotein protection can improve the quality of frozen bovine sperm. 35870621 8 23 gly glycosylated 1358:1369 arg1 proteins 1371:1378 glycosylated proteins 1358:1378 glycosylated proteins 1358:1378 Mostly key regulators were identified to be glycoproteins, which confirms that glycosylated proteins played important roles in bovine sperm. 35870621 7 24 theme biologic 1131:1138 arg1 functions 1140:1148 The biologic functions 1127:1148 The biologic functions of the 115 changed proteins 1127:1176 The biologic functions of the 115 changed proteins are mainly involved in sperm capacitation, migration in female genitalia, and sperm-egg interaction. 35870621 9 25 theme effective 1568:1576 arg1 way 1578:1580 an effective way 1565:1580 an effective way to improve the quality of frozen sperm 1565:1619 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 9 25 theme effective 1568:1576 arg1 protection 1544:1553 glycoprotein protection 1531:1553 glycoprotein protection 1531:1553 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 6 26 dep glycoproteins 1086:1098 arg1 glycoproteins 1086:1098 glycoproteins TEX101, ACRBP, and IZOMU4 1086:1124 glycoproteins TEX101, ACRBP, and IZOMU4 1086:1124 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 6 26 dep glycoproteins 1086:1098 arg1 ACRBP 1108:1112 ACRBP 1108:1112 ACRBP 1108:1112 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 6 26 dep glycoproteins 1086:1098 arg1 IZOMU4 1119:1124 IZOMU4 1119:1124 IZOMU4 1119:1124 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 6 26 dep glycoproteins 1086:1098 arg1 TEX101 1100:1105 TEX101 1100:1105 TEX101 1100:1105 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 3 27 theme cryopreservation 448:463 arg1 effect 438:443 the effect 434:443 the effect of cryopreservation on glycoproteins of bovine spermatozoa 434:502 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 0 28 theme quantitative 10:21 arg1 analysis 40:47 TMT-based quantitative N-glycoproteomic analysis 0:47 TMT-based quantitative N-glycoproteomic analysis 0:47 TMT-based quantitative N-glycoproteomic analysis reveals glycoprotein protection can improve the quality of frozen bovine sperm. 35870621 7 29 from capacitation 1207:1218 arg1 genitalia 1241:1249 female genitalia 1234:1249 female genitalia 1234:1249 The biologic functions of the 115 changed proteins are mainly involved in sperm capacitation, migration in female genitalia, and sperm-egg interaction. 35870621 3 30 theme TMT 565:567 arg1 glycoproteome 591:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 3 31 theme first 529:533 arg1 time 535:538 the first time 525:538 the first time 525:538 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 1 32 theme genetic 197:203 arg1 improvement 205:215 genetic improvement 197:215 genetic improvement 197:215 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 0 33 theme TMT-based 0:8 arg1 analysis 40:47 TMT-based quantitative N-glycoproteomic analysis 0:47 TMT-based quantitative N-glycoproteomic analysis 0:47 TMT-based quantitative N-glycoproteomic analysis reveals glycoprotein protection can improve the quality of frozen bovine sperm. 35870621 4 34 gly glycoproteins 639:651 arg1 glycoproteins 639:651 492 glycoproteins 635:651 492 glycoproteins 635:651 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 8 35 theme bovine 1406:1411 arg1 sperm 1413:1417 bovine sperm 1406:1417 bovine sperm 1406:1417 Mostly key regulators were identified to be glycoproteins, which confirms that glycosylated proteins played important roles in bovine sperm. 35870621 5 36 theme Thirty-three 816:827 arg1 glycoproteins 838:850 glycoproteins 838:850 glycoproteins 838:850 Thirty-three DEPs are glycoproteins, which demonstrates that glycoproteins of bovine sperm were seriously affected by cryopreservation. 35870621 5 36 theme Thirty-three 816:827 arg1 DEPs 829:832 Thirty-three DEPs 816:832 Thirty-three DEPs 816:832 Thirty-three DEPs are glycoproteins, which demonstrates that glycoproteins of bovine sperm were seriously affected by cryopreservation. 35870621 6 37 gly glycoproteins 1086:1098 arg1 glycoproteins 1086:1098 glycoproteins TEX101, ACRBP, and IZOMU4 1086:1124 glycoproteins TEX101, ACRBP, and IZOMU4 1086:1124 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 6 37 gly glycoproteins 1086:1098 arg1 ACRBP 1108:1112 ACRBP 1108:1112 ACRBP 1108:1112 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 6 37 gly glycoproteins 1086:1098 arg1 IZOMU4 1119:1124 IZOMU4 1119:1124 IZOMU4 1119:1124 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 6 37 gly glycoproteins 1086:1098 arg1 TEX101 1100:1105 TEX101 1100:1105 TEX101 1100:1105 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 6 38 gly glycoprotein 982:993 arg1 glycoprotein 982:993 glycoprotein expression 982:1004 glycoprotein expression 982:1004 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 3 39 theme tag 560:562 arg1 glycoproteome 591:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 0 40 theme N-glycoproteomic 23:38 arg1 analysis 40:47 TMT-based quantitative N-glycoproteomic analysis 0:47 TMT-based quantitative N-glycoproteomic analysis 0:47 TMT-based quantitative N-glycoproteomic analysis reveals glycoprotein protection can improve the quality of frozen bovine sperm. 35870621 6 41 theme glycoprotein 982:993 arg1 expression 995:1004 glycoprotein expression 982:1004 glycoprotein expression 982:1004 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 35870621 2 42 contain has 386:388 arg1 modification 362:373 The glycosylation modification 344:373 The glycosylation modification of protein 344:384 The glycosylation modification of protein has irreplaceable roles in spermatozoa. 35870621 2 42 contain has 386:388 arg2 roles 404:408 irreplaceable roles 390:408 irreplaceable roles 390:408 The glycosylation modification of protein has irreplaceable roles in spermatozoa. 35870621 4 43 theme expression 693:702 arg1 DEPs 714:717 DEPs 714:717 DEPs 714:717 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 4 43 theme expression 693:702 arg1 proteins 704:711 83 different expression proteins 680:711 83 different expression proteins (DEPs) 680:718 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 1 44 theme elite 221:225 arg1 breeding 227:234 elite breeding 221:234 elite breeding 221:234 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 0 45 theme glycoprotein 57:68 arg1 protection 70:79 glycoprotein protection 57:79 glycoprotein protection 57:79 TMT-based quantitative N-glycoproteomic analysis reveals glycoprotein protection can improve the quality of frozen bovine sperm. 35870621 9 46 theme sperm 1615:1619 arg1 quality 1597:1603 the quality 1593:1603 the quality of frozen sperm 1593:1619 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 7 47 from migration 1221:1229 arg1 genitalia 1241:1249 female genitalia 1234:1249 female genitalia 1234:1249 The biologic functions of the 115 changed proteins are mainly involved in sperm capacitation, migration in female genitalia, and sperm-egg interaction. 35870621 4 48 theme glycoproteins 639:651 arg1 total 608:612 A total 606:612 A total of 2598 proteins and 492 glycoproteins 606:651 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 4 49 theme different 683:691 arg1 DEPs 714:717 DEPs 714:717 DEPs 714:717 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 4 49 theme different 683:691 arg1 proteins 704:711 83 different expression proteins 680:711 83 different expression proteins (DEPs) 680:718 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 1 50 contain has 244:246 arg2 effect 262:267 a detrimental effect 248:267 a detrimental effect 248:267 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 1 50 contain has 244:246 arg1 it 241:242 it 241:242 it 241:242 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 9 51 theme glycoproteins 1454:1466 arg1 study 1439:1443 This comprehensive study 1420:1443 This comprehensive study of sperm glycoproteins 1420:1466 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 4 52 gly glycosylated 748:759 arg1 DEGPs 771:775 DEGPs 771:775 DEGPs 771:775 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 4 52 gly glycosylated 748:759 arg1 proteins 761:768 44 different expression glycosylated proteins 724:768 44 different expression glycosylated proteins (DEGPs) 724:776 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 7 53 theme changed 1161:1167 arg1 proteins 1169:1176 the 115 changed proteins 1153:1176 the 115 changed proteins 1153:1176 The biologic functions of the 115 changed proteins are mainly involved in sperm capacitation, migration in female genitalia, and sperm-egg interaction. 35870621 5 54 theme bovine 894:899 arg1 sperm 901:905 bovine sperm 894:905 bovine sperm 894:905 Thirty-three DEPs are glycoproteins, which demonstrates that glycoproteins of bovine sperm were seriously affected by cryopreservation. 35870621 8 55 theme important 1387:1395 arg1 roles 1397:1401 important roles 1387:1401 important roles 1387:1401 Mostly key regulators were identified to be glycoproteins, which confirms that glycosylated proteins played important roles in bovine sperm. 35870621 3 56 gly glycoproteins 468:480 arg1 glycoproteins 468:480 glycoproteins 468:480 glycoproteins of bovine spermatozoa 468:502 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 4 57 dep glycosylated 748:759 arg1 expression 737:746 expression 737:746 expression 737:746 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 7 58 theme proteins 1169:1176 arg1 functions 1140:1148 The biologic functions 1127:1148 The biologic functions of the 115 changed proteins 1127:1176 The biologic functions of the 115 changed proteins are mainly involved in sperm capacitation, migration in female genitalia, and sperm-egg interaction. 35870621 3 59 theme quantitative 578:589 arg1 glycoproteome 591:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 a tandem mass tag (TMT)-labeled quantitative glycoproteome 546:603 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 7 60 theme female 1234:1239 arg1 genitalia 1241:1249 female genitalia 1234:1249 female genitalia 1234:1249 The biologic functions of the 115 changed proteins are mainly involved in sperm capacitation, migration in female genitalia, and sperm-egg interaction. 35870621 7 61 theme sperm 1201:1205 arg1 capacitation 1207:1218 sperm capacitation 1201:1218 sperm capacitation 1201:1218 The biologic functions of the 115 changed proteins are mainly involved in sperm capacitation, migration in female genitalia, and sperm-egg interaction. 35870621 4 62 theme fresh 786:790 arg1 spermatozoa 803:813 fresh and frozen spermatozoa 786:813 fresh and frozen spermatozoa 786:813 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 8 63 theme key 1286:1288 arg1 regulators 1290:1299 Mostly key regulators 1279:1299 Mostly key regulators 1279:1299 Mostly key regulators were identified to be glycoproteins, which confirms that glycosylated proteins played important roles in bovine sperm. 35870621 1 64 theme bovine 149:154 arg1 semen 156:160 bovine semen 149:160 bovine semen 149:160 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 4 65 theme glycosylated 748:759 arg1 DEGPs 771:775 DEGPs 771:775 DEGPs 771:775 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 4 65 theme glycosylated 748:759 arg1 proteins 761:768 44 different expression glycosylated proteins 724:768 44 different expression glycosylated proteins (DEGPs) 724:776 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 9 66 theme comprehensive 1425:1437 arg1 study 1439:1443 This comprehensive study 1420:1443 This comprehensive study of sperm glycoproteins 1420:1466 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 9 67 theme frozen 1608:1613 arg1 sperm 1615:1619 frozen sperm 1608:1619 frozen sperm 1608:1619 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 9 68 gly glycoprotein 1531:1542 arg1 glycoprotein 1531:1542 glycoprotein protection 1531:1553 glycoprotein protection 1531:1553 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 0 69 gly glycoprotein 57:68 arg1 glycoprotein 57:68 glycoprotein protection 57:79 glycoprotein protection 57:79 TMT-based quantitative N-glycoproteomic analysis reveals glycoprotein protection can improve the quality of frozen bovine sperm. 35870621 1 70 theme semen 156:160 arg1 Cryopreservation 129:144 Cryopreservation 129:144 Cryopreservation of bovine semen 129:160 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 3 71 theme spermatozoa 492:502 arg1 glycoproteins 468:480 glycoproteins 468:480 glycoproteins of bovine spermatozoa 468:502 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 9 72 theme glycoprotein 1531:1542 arg1 way 1578:1580 an effective way 1565:1580 an effective way to improve the quality of frozen sperm 1565:1619 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 9 72 theme glycoprotein 1531:1542 arg1 protection 1544:1553 glycoprotein protection 1531:1553 glycoprotein protection 1531:1553 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 4 73 theme 492 635:637 arg1 glycoproteins 639:651 492 glycoproteins 635:651 492 glycoproteins 635:651 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 4 74 theme frozen 796:801 arg1 spermatozoa 803:813 fresh and frozen spermatozoa 786:813 fresh and frozen spermatozoa 786:813 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 3 75 from effect 438:443 arg1 glycoproteins 468:480 glycoproteins 468:480 glycoproteins of bovine spermatozoa 468:502 Herein, the effect of cryopreservation on glycoproteins of bovine spermatozoa has been studied for the first time using a tandem mass tag (TMT)-labeled quantitative glycoproteome. 35870621 2 76 theme protein 378:384 arg1 modification 362:373 The glycosylation modification 344:373 The glycosylation modification of protein 344:384 The glycosylation modification of protein has irreplaceable roles in spermatozoa. 35870621 9 77 theme cryoinjury 1489:1498 arg1 mechanisms 1500:1509 the cryoinjury mechanisms 1485:1509 the cryoinjury mechanisms 1485:1509 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 4 78 theme 2598 617:620 arg1 proteins 622:629 2598 proteins 617:629 2598 proteins 617:629 A total of 2598 proteins and 492 glycoproteins were identified, including 83 different expression proteins (DEPs) and 44 different expression glycosylated proteins (DEGPs) between fresh and frozen spermatozoa. 35870621 7 79 theme sperm-egg 1256:1264 arg1 interaction 1266:1276 sperm-egg interaction 1256:1276 sperm-egg interaction 1256:1276 The biologic functions of the 115 changed proteins are mainly involved in sperm capacitation, migration in female genitalia, and sperm-egg interaction. 35870621 1 80 theme reproductive 319:330 arg1 efficiency 332:341 the reproductive efficiency 315:341 the reproductive efficiency 315:341 Cryopreservation of bovine semen plays a vital role in accelerating genetic improvement and elite breeding, but it has a detrimental effect on sperm quality, resulting in the decline of the reproductive efficiency. 35870621 9 81 theme sperm 1448:1452 arg1 glycoproteins 1454:1466 sperm glycoproteins 1448:1466 sperm glycoproteins 1448:1466 This comprehensive study of sperm glycoproteins helps to unravel the cryoinjury mechanisms, thus implying that glycoprotein protection should be an effective way to improve the quality of frozen sperm. 35870621 5 82 theme sperm 901:905 arg1 glycoproteins 877:889 glycoproteins 877:889 glycoproteins of bovine sperm 877:905 Thirty-three DEPs are glycoproteins, which demonstrates that glycoproteins of bovine sperm were seriously affected by cryopreservation. 35870621 6 83 theme substructure 1039:1050 arg1 localization 1052:1063 substructure localization 1039:1063 substructure localization 1039:1063 Moreover, the effects include glycoprotein expression, glycosylation modification, and substructure localization for proteins such as glycoproteins TEX101, ACRBP, and IZOMU4. 37074911 5 0 theme glycosylation 611:623 arg1 profiles 625:632 distinct glycosylation profiles 602:632 distinct glycosylation profiles 602:632 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 8 1 theme tandem 993:998 arg1 resource 1096:1103 a valuable resource 1085:1103 a valuable resource for the community 1085:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 1 theme tandem 993:998 arg1 analysis 1049:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis 979:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community 979:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 7 2 gly glycosylation 879:891 arg1 ccRCC 896:900 ccRCC development 896:912 ccRCC development 896:912 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 4 3 theme comprehensive 350:362 arg1 analysis 379:386 a comprehensive glycoproteomic analysis 348:386 a comprehensive glycoproteomic analysis 348:386 Here, a comprehensive glycoproteomic analysis is conducted using 103 tumors and 80 paired normal adjacent tissues. 37074911 1 4 theme RCC 137:139 arg1 form 129:132 a common form 120:132 a common form of RCC 120:139 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 4 theme RCC 137:139 arg1 carcinoma 101:109 Clear cell renal cell carcinoma 79:109 Clear cell renal cell carcinoma (ccRCC) 79:117 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 8 5 theme ccRCC 1061:1065 arg1 resource 1096:1103 a valuable resource 1085:1103 a valuable resource for the community 1085:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 5 theme ccRCC 1061:1065 arg1 analysis 1049:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis 979:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community 979:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 7 6 from role 871:874 arg1 development 902:912 ccRCC development 896:912 ccRCC development 896:912 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 8 7 theme tag 1005:1007 arg1 resource 1096:1103 a valuable resource 1085:1103 a valuable resource for the community 1085:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 7 theme tag 1005:1007 arg1 analysis 1049:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis 979:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community 979:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 7 8 theme ccRCC 896:900 arg1 development 902:912 ccRCC development 896:912 ccRCC development 896:912 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 8 9 theme large-scale 981:991 arg1 resource 1096:1103 a valuable resource 1085:1103 a valuable resource for the community 1085:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 9 theme large-scale 981:991 arg1 analysis 1049:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis 979:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community 979:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 4 10 theme adjacent 439:446 arg1 tissues 448:454 80 paired normal adjacent tissues 422:454 80 paired normal adjacent tissues 422:454 Here, a comprehensive glycoproteomic analysis is conducted using 103 tumors and 80 paired normal adjacent tissues. 37074911 5 11 theme Altered 457:463 arg1 enzymes 479:485 Altered glycosylation enzymes 457:485 Altered glycosylation enzymes 457:485 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 4 12 theme normal 432:437 arg1 tissues 448:454 80 paired normal adjacent tissues 422:454 80 paired normal adjacent tissues 422:454 Here, a comprehensive glycoproteomic analysis is conducted using 103 tumors and 80 paired normal adjacent tissues. 37074911 4 13 theme glycoproteomic 364:377 arg1 analysis 379:386 a comprehensive glycoproteomic analysis 348:386 a comprehensive glycoproteomic analysis 348:386 Here, a comprehensive glycoproteomic analysis is conducted using 103 tumors and 80 paired normal adjacent tissues. 37074911 1 14 theme Clear 79:83 arg1 form 129:132 a common form 120:132 a common form of RCC 120:139 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 14 theme Clear 79:83 arg1 ccRCC 112:116 ccRCC 112:116 ccRCC 112:116 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 14 theme Clear 79:83 arg1 carcinoma 101:109 Clear cell renal cell carcinoma 79:109 Clear cell renal cell carcinoma (ccRCC) 79:117 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 5 15 theme glycosylation 465:477 arg1 enzymes 479:485 Altered glycosylation enzymes 457:485 Altered glycosylation enzymes 457:485 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 8 16 theme quantitative 1021:1032 arg1 resource 1096:1103 a valuable resource 1085:1103 a valuable resource for the community 1085:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 16 theme quantitative 1021:1032 arg1 analysis 1049:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis 979:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community 979:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 1 17 theme cell 85:88 arg1 form 129:132 a common form 120:132 a common form of RCC 120:139 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 17 theme cell 85:88 arg1 ccRCC 112:116 ccRCC 112:116 ccRCC 112:116 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 17 theme cell 85:88 arg1 carcinoma 101:109 Clear cell renal cell carcinoma 79:109 Clear cell renal cell carcinoma (ccRCC) 79:117 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 0 18 theme glycoproteomic 11:24 arg1 characterization 26:41 glycoproteomic characterization 11:41 glycoproteomic characterization of clear cell renal cell carcinoma 11:76 Integrated glycoproteomic characterization of clear cell renal cell carcinoma. 37074911 8 19 theme valuable 1087:1094 arg1 resource 1096:1103 a valuable resource 1085:1103 a valuable resource for the community 1085:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 19 theme valuable 1087:1094 arg1 analysis 1049:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis 979:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community 979:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 20 theme -based 1014:1019 arg1 resource 1096:1103 a valuable resource 1085:1103 a valuable resource for the community 1085:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 20 theme -based 1014:1019 arg1 analysis 1049:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis 979:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community 979:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 1 21 theme renal 90:94 arg1 form 129:132 a common form 120:132 a common form of RCC 120:139 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 21 theme renal 90:94 arg1 ccRCC 112:116 ccRCC 112:116 ccRCC 112:116 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 21 theme renal 90:94 arg1 carcinoma 101:109 Clear cell renal cell carcinoma 79:109 Clear cell renal cell carcinoma (ccRCC) 79:117 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 7 22 theme proteomic 821:829 arg1 changes 853:859 genomic, transcriptomic, proteomic, and phosphoproteomic changes 796:859 genomic, transcriptomic, proteomic, and phosphoproteomic changes 796:859 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 5 23 theme distinct 602:609 arg1 profiles 625:632 distinct glycosylation profiles 602:632 distinct glycosylation profiles 602:632 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 5 24 theme major 558:562 arg1 mutations 570:578 the major ccRCC mutations 554:578 the major ccRCC mutations 554:578 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 1 25 theme cell 96:99 arg1 form 129:132 a common form 120:132 a common form of RCC 120:139 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 25 theme cell 96:99 arg1 ccRCC 112:116 ccRCC 112:116 ccRCC 112:116 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 25 theme cell 96:99 arg1 carcinoma 101:109 Clear cell renal cell carcinoma 79:109 Clear cell renal cell carcinoma (ccRCC) 79:117 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 5 26 theme ccRCC 564:568 arg1 mutations 570:578 the major ccRCC mutations 554:578 the major ccRCC mutations 554:578 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 5 27 theme mutations 570:578 arg1 PBRM1 590:594 PBRM1 590:594 PBRM1 590:594 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 5 27 theme mutations 570:578 arg1 BAP1 581:584 BAP1 581:584 BAP1 581:584 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 5 27 theme mutations 570:578 arg1 mutations 570:578 the major ccRCC mutations 554:578 the major ccRCC mutations 554:578 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 5 27 theme mutations 570:578 arg1 two 547:549 two 547:549 two 547:549 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 7 28 theme transcriptomic 805:818 arg1 changes 853:859 genomic, transcriptomic, proteomic, and phosphoproteomic changes 796:859 genomic, transcriptomic, proteomic, and phosphoproteomic changes 796:859 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 6 29 theme inter-tumor 649:659 arg1 heterogeneity 661:673 inter-tumor heterogeneity 649:673 inter-tumor heterogeneity 649:673 Additionally, inter-tumor heterogeneity and cross-correlation between glycosylation and phosphorylation are observed. 37074911 1 30 theme high 165:168 arg1 rate 180:183 the high mortality rate 161:183 the high mortality rate of kidney cancer 161:200 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 0 31 theme cell 52:55 arg1 carcinoma 68:76 clear cell renal cell carcinoma 46:76 clear cell renal cell carcinoma 46:76 Integrated glycoproteomic characterization of clear cell renal cell carcinoma. 37074911 7 32 theme glycosylation 879:891 arg1 role 871:874 the role 867:874 the role of glycosylation in ccRCC development 867:912 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 7 33 theme phosphoproteomic 836:851 arg1 changes 853:859 genomic, transcriptomic, proteomic, and phosphoproteomic changes 796:859 genomic, transcriptomic, proteomic, and phosphoproteomic changes 796:859 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 1 34 theme mortality 170:178 arg1 rate 180:183 the high mortality rate 161:183 the high mortality rate of kidney cancer 161:200 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 0 35 theme clear 46:50 arg1 carcinoma 68:76 clear cell renal cell carcinoma 46:76 clear cell renal cell carcinoma 46:76 Integrated glycoproteomic characterization of clear cell renal cell carcinoma. 37074911 7 36 theme genomic 796:802 arg1 changes 853:859 genomic, transcriptomic, proteomic, and phosphoproteomic changes 796:859 genomic, transcriptomic, proteomic, and phosphoproteomic changes 796:859 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 4 37 theme paired 425:430 arg1 tissues 448:454 80 paired normal adjacent tissues 422:454 80 paired normal adjacent tissues 422:454 Here, a comprehensive glycoproteomic analysis is conducted using 103 tumors and 80 paired normal adjacent tissues. 37074911 0 38 theme cell 63:66 arg1 carcinoma 68:76 clear cell renal cell carcinoma 46:76 clear cell renal cell carcinoma 46:76 Integrated glycoproteomic characterization of clear cell renal cell carcinoma. 37074911 0 39 theme renal 57:61 arg1 carcinoma 68:76 clear cell renal cell carcinoma 46:76 clear cell renal cell carcinoma 46:76 Integrated glycoproteomic characterization of clear cell renal cell carcinoma. 37074911 7 40 theme features 784:791 arg1 relation 757:764 The relation 753:764 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes 753:859 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 7 41 theme therapeutic 933:943 arg1 interventions 945:957 therapeutic interventions 933:957 therapeutic interventions 933:957 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 8 42 theme glycoproteomic 1034:1047 arg1 resource 1096:1103 a valuable resource 1085:1103 a valuable resource for the community 1085:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 42 theme glycoproteomic 1034:1047 arg1 analysis 1049:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis 979:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community 979:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 43 theme TMT 1010:1012 arg1 resource 1096:1103 a valuable resource 1085:1103 a valuable resource for the community 1085:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 43 theme TMT 1010:1012 arg1 analysis 1049:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis 979:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community 979:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 2 44 theme glycoproteins 221:233 arg1 Dysregulations 203:216 Dysregulations 203:216 Dysregulations of glycoproteins 203:233 Dysregulations of glycoproteins have been shown to associate with ccRCC. 37074911 5 45 theme corresponding 491:503 arg1 glycosylation 513:525 corresponding protein glycosylation 491:525 corresponding protein glycosylation 491:525 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 1 46 theme kidney 188:193 arg1 cancer 195:200 kidney cancer 188:200 kidney cancer 188:200 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 3 47 theme molecular 289:297 arg1 mechanism 299:307 the molecular mechanism 285:307 the molecular mechanism 285:307 However, the molecular mechanism has not been well characterized. 37074911 7 48 theme glycoproteomic 769:782 arg1 features 784:791 glycoproteomic features 769:791 glycoproteomic features 769:791 The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. 37074911 5 49 theme protein 505:511 arg1 glycosylation 513:525 corresponding protein glycosylation 491:525 corresponding protein glycosylation 491:525 Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. 37074911 1 50 theme common 122:127 arg1 form 129:132 a common form 120:132 a common form of RCC 120:139 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 50 theme common 122:127 arg1 carcinoma 101:109 Clear cell renal cell carcinoma 79:109 Clear cell renal cell carcinoma (ccRCC) 79:117 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 1 51 theme cancer 195:200 arg1 rate 180:183 the high mortality rate 161:183 the high mortality rate of kidney cancer 161:200 Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. 37074911 0 52 theme carcinoma 68:76 arg1 characterization 26:41 glycoproteomic characterization 11:41 glycoproteomic characterization of clear cell renal cell carcinoma 11:76 Integrated glycoproteomic characterization of clear cell renal cell carcinoma. 37074911 8 53 theme mass 1000:1003 arg1 resource 1096:1103 a valuable resource 1085:1103 a valuable resource for the community 1085:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 8 53 theme mass 1000:1003 arg1 analysis 1049:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis 979:1056 a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community 979:1121 This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community. 37074911 2 54 gly glycoproteins 221:233 arg1 glycoproteins 221:233 glycoproteins 221:233 glycoproteins 221:233 Dysregulations of glycoproteins have been shown to associate with ccRCC. 37224467 5 0 theme promoter-driven 646:660 arg1 Ogt-FKO 679:685 Ogt-FKO 679:685 Ogt-FKO 679:685 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 5 0 theme promoter-driven 646:660 arg1 recombinase 666:676 adiponectin promoter-driven Cre recombinase 634:676 adiponectin promoter-driven Cre recombinase (Ogt-FKO) 634:686 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 10 1 from conclusion 1453:1462 arg1 important 1484:1492 important 1484:1492 important 1484:1492 In conclusion, O-GlcNAcylation is important for healthy adipose expansion in mice. 37224467 0 2 theme high-fat 82:89 arg1 feeding 91:97 high-fat feeding 82:97 high-fat feeding 82:97 O-GlcNAc modification is essential for physiological adipose expansion induced by high-fat feeding. 37224467 6 3 theme genes 915:919 arg1 gain 854:857 their reduced bodyweight gain 829:857 their reduced bodyweight gain 829:857 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 6 3 theme genes 915:919 arg1 expression 881:890 decreased expression 871:890 decreased expression of de novo lipogenesis genes 871:919 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 6 3 theme genes 915:919 arg1 expression 935:944 increased expression 925:944 increased expression of inflammatory genes 925:966 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 5 4 theme Cre 662:664 arg1 Ogt-FKO 679:685 Ogt-FKO 679:685 Ogt-FKO 679:685 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 5 4 theme Cre 662:664 arg1 recombinase 666:676 adiponectin promoter-driven Cre recombinase 634:676 adiponectin promoter-driven Cre recombinase (Ogt-FKO) 634:686 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 5 5 with Mice 575:578 arg1 knockout 585:592 knockout 585:592 knockout 585:592 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 1 6 theme metabolic 170:178 arg1 homeostasis 180:190 metabolic homeostasis 170:190 metabolic homeostasis 170:190 Adipose tissues accumulate excess energy as fat and heavily influence metabolic homeostasis. 37224467 9 7 from cause 1403:1407 arg1 mice 1444:1447 Ogt-FKO mice 1436:1447 Ogt-FKO mice 1436:1447 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 6 8 theme lipogenesis 903:913 arg1 genes 915:919 de novo lipogenesis genes 895:919 de novo lipogenesis genes 895:919 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 4 9 from O-GlcNAcylation 509:523 arg1 mice 528:531 mice 528:531 mice with high-fat diet (HFD)-induced obesity 528:572 Here, we report on O-GlcNAcylation in mice with high-fat diet (HFD)-induced obesity. 37224467 5 10 theme Ogt 597:599 arg1 knockout 585:592 knockout 585:592 knockout 585:592 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 9 11 attach derived 1242:1248 arg1 adipocytes 1261:1270 these adipocytes 1255:1270 these adipocytes 1255:1270 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 9 11 attach derived 1242:1248 arg2 Medium 1235:1240 Medium 1235:1240 Medium derived from these adipocytes 1235:1270 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 8 12 theme Ogt 1173:1175 arg1 inhibitor 1177:1185 Ogt inhibitor 1173:1185 Ogt inhibitor 1173:1185 Both in primary cultured adipocytes and 3T3-L1 adipocytes treated with Ogt inhibitor showed increased secretion of free fatty acids. 37224467 8 13 theme increased 1194:1202 arg1 secretion 1204:1212 increased secretion 1194:1212 increased secretion of free fatty acids 1194:1232 Both in primary cultured adipocytes and 3T3-L1 adipocytes treated with Ogt inhibitor showed increased secretion of free fatty acids. 37224467 4 14 with mice 528:531 arg1 obesity 566:572 high-fat diet (HFD)-induced obesity 538:572 high-fat diet (HFD)-induced obesity 538:572 Here, we report on O-GlcNAcylation in mice with high-fat diet (HFD)-induced obesity. 37224467 5 15 theme adipose 604:610 arg1 tissue 612:617 adipose tissue 604:617 adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) 604:686 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 2 16 theme O-GlcNAc 300:307 arg1 transferase 309:319 O-GlcNAc transferase 300:319 O-GlcNAc transferase (Ogt) 300:325 O-GlcNAc modification (O-GlcNAcylation), which involves the addition of N-acetylglucosamine to proteins by O-GlcNAc transferase (Ogt), modulates multiple cellular processes. 37224467 2 16 theme O-GlcNAc 300:307 arg1 Ogt 322:324 Ogt 322:324 Ogt 322:324 O-GlcNAc modification (O-GlcNAcylation), which involves the addition of N-acetylglucosamine to proteins by O-GlcNAc transferase (Ogt), modulates multiple cellular processes. 37224467 3 17 theme bodyweight 452:461 arg1 gain 463:466 bodyweight gain 452:466 bodyweight gain due to overnutrition 452:487 However, little is known about the role of O-GlcNAcylation in adipose tissues during bodyweight gain due to overnutrition. 37224467 0 18 theme adipose 53:59 arg1 expansion 61:69 physiological adipose expansion 39:69 physiological adipose expansion induced by high-fat feeding 39:97 O-GlcNAc modification is essential for physiological adipose expansion induced by high-fat feeding. 37224467 9 19 theme RAW 1305:1307 arg1 macrophages 1315:1325 RAW 264.7 macrophages 1305:1325 RAW 264.7 macrophages 1305:1325 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 6 20 theme insulin 801:807 arg1 resistance 809:818 insulin resistance 801:818 insulin resistance 801:818 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 7 21 attach derived 1039:1045 arg2 adipocytes 1028:1037 Primary cultured adipocytes 1011:1037 Primary cultured adipocytes derived from Ogt-FKO mice 1011:1063 Primary cultured adipocytes derived from Ogt-FKO mice showed decreased lipid accumulation. 37224467 7 21 attach derived 1039:1045 arg1 mice 1060:1063 Ogt-FKO mice 1052:1063 Ogt-FKO mice 1052:1063 Primary cultured adipocytes derived from Ogt-FKO mice showed decreased lipid accumulation. 37224467 3 22 from role 402:405 arg1 tissues 437:443 adipose tissues 429:443 adipose tissues during bodyweight gain due to overnutrition 429:487 However, little is known about the role of O-GlcNAcylation in adipose tissues during bodyweight gain due to overnutrition. 37224467 10 23 theme healthy 1498:1504 arg1 expansion 1514:1522 healthy adipose expansion 1498:1522 healthy adipose expansion in mice 1498:1530 In conclusion, O-GlcNAcylation is important for healthy adipose expansion in mice. 37224467 9 24 theme free 1375:1378 arg1 acids 1386:1390 free fatty acids 1375:1390 free fatty acids 1375:1390 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 6 25 theme de 895:896 arg1 genes 915:919 de novo lipogenesis genes 895:919 de novo lipogenesis genes 895:919 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 0 26 theme O-GlcNAc 0:7 arg1 modification 9:20 O-GlcNAc modification 0:20 O-GlcNAc modification 0:20 O-GlcNAc modification is essential for physiological adipose expansion induced by high-fat feeding. 37224467 8 27 theme primary 1110:1116 arg1 adipocytes 1127:1136 primary cultured adipocytes 1110:1136 primary cultured adipocytes 1110:1136 Both in primary cultured adipocytes and 3T3-L1 adipocytes treated with Ogt inhibitor showed increased secretion of free fatty acids. 37224467 5 28 theme adiponectin 634:644 arg1 Ogt-FKO 679:685 Ogt-FKO 679:685 Ogt-FKO 679:685 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 5 28 theme adiponectin 634:644 arg1 recombinase 666:676 adiponectin promoter-driven Cre recombinase 634:676 adiponectin promoter-driven Cre recombinase (Ogt-FKO) 634:686 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 1 29 theme Adipose 100:106 arg1 tissues 108:114 Adipose tissues 100:114 Adipose tissues 100:114 Adipose tissues accumulate excess energy as fat and heavily influence metabolic homeostasis. 37224467 9 30 theme Ogt-FKO 1436:1442 arg1 mice 1444:1447 Ogt-FKO mice 1436:1447 Ogt-FKO mice 1436:1447 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 8 31 theme fatty 1222:1226 arg1 acids 1228:1232 free fatty acids 1217:1232 free fatty acids 1217:1232 Both in primary cultured adipocytes and 3T3-L1 adipocytes treated with Ogt inhibitor showed increased secretion of free fatty acids. 37224467 9 32 theme fatty 1380:1384 arg1 acids 1386:1390 free fatty acids 1375:1390 free fatty acids 1375:1390 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 7 33 theme decreased 1072:1080 arg1 accumulation 1088:1099 decreased lipid accumulation 1072:1099 decreased lipid accumulation 1072:1099 Primary cultured adipocytes derived from Ogt-FKO mice showed decreased lipid accumulation. 37224467 6 34 theme glucose 777:783 arg1 intolerance 785:795 glucose intolerance 777:795 glucose intolerance 777:795 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 8 35 theme free 1217:1220 arg1 acids 1228:1232 free fatty acids 1217:1232 free fatty acids 1217:1232 Both in primary cultured adipocytes and 3T3-L1 adipocytes treated with Ogt inhibitor showed increased secretion of free fatty acids. 37224467 10 36 from important 1484:1492 arg1 conclusion 1453:1462 conclusion 1453:1462 conclusion 1453:1462 In conclusion, O-GlcNAcylation is important for healthy adipose expansion in mice. 37224467 7 37 theme lipid 1082:1086 arg1 accumulation 1088:1099 decreased lipid accumulation 1072:1099 decreased lipid accumulation 1072:1099 Primary cultured adipocytes derived from Ogt-FKO mice showed decreased lipid accumulation. 37224467 6 38 theme decreased 871:879 arg1 expression 881:890 decreased expression 871:890 decreased expression of de novo lipogenesis genes 871:919 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 5 39 from Ogt 597:599 arg1 tissue 612:617 adipose tissue 604:617 adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) 604:686 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 0 40 theme physiological 39:51 arg1 expansion 61:69 physiological adipose expansion 39:69 physiological adipose expansion induced by high-fat feeding 39:97 O-GlcNAc modification is essential for physiological adipose expansion induced by high-fat feeding. 37224467 4 41 theme -induced 557:564 arg1 obesity 566:572 high-fat diet (HFD)-induced obesity 538:572 high-fat diet (HFD)-induced obesity 538:572 Here, we report on O-GlcNAcylation in mice with high-fat diet (HFD)-induced obesity. 37224467 5 42 theme control 716:722 arg1 mice 724:727 control mice 716:727 control mice 716:727 Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less bodyweight than control mice under HFD. 37224467 2 43 theme O-GlcNAc 193:200 arg1 O-GlcNAcylation 216:230 O-GlcNAcylation 216:230 O-GlcNAcylation 216:230 O-GlcNAc modification (O-GlcNAcylation), which involves the addition of N-acetylglucosamine to proteins by O-GlcNAc transferase (Ogt), modulates multiple cellular processes. 37224467 2 43 theme O-GlcNAc 193:200 arg1 modification 202:213 O-GlcNAc modification 193:213 O-GlcNAc modification (O-GlcNAcylation) 193:231 O-GlcNAc modification (O-GlcNAcylation), which involves the addition of N-acetylglucosamine to proteins by O-GlcNAc transferase (Ogt), modulates multiple cellular processes. 37224467 3 44 theme adipose 429:435 arg1 tissues 437:443 adipose tissues 429:443 adipose tissues during bodyweight gain due to overnutrition 429:487 However, little is known about the role of O-GlcNAcylation in adipose tissues during bodyweight gain due to overnutrition. 37224467 4 45 theme high-fat 538:545 arg1 diet 547:550 high-fat diet 538:550 high-fat diet (HFD) 538:556 Here, we report on O-GlcNAcylation in mice with high-fat diet (HFD)-induced obesity. 37224467 4 45 theme high-fat 538:545 arg1 HFD 553:555 HFD 553:555 HFD 553:555 Here, we report on O-GlcNAcylation in mice with high-fat diet (HFD)-induced obesity. 37224467 8 46 theme acids 1228:1232 arg1 secretion 1204:1212 increased secretion 1194:1212 increased secretion of free fatty acids 1194:1232 Both in primary cultured adipocytes and 3T3-L1 adipocytes treated with Ogt inhibitor showed increased secretion of free fatty acids. 37224467 7 47 theme Primary 1011:1017 arg1 adipocytes 1028:1037 Primary cultured adipocytes 1011:1037 Primary cultured adipocytes derived from Ogt-FKO mice 1011:1063 Primary cultured adipocytes derived from Ogt-FKO mice showed decreased lipid accumulation. 37224467 6 48 theme genes 962:966 arg1 gain 854:857 their reduced bodyweight gain 829:857 their reduced bodyweight gain 829:857 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 6 48 theme genes 962:966 arg1 expression 881:890 decreased expression 871:890 decreased expression of de novo lipogenesis genes 871:919 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 6 48 theme genes 962:966 arg1 expression 935:944 increased expression 925:944 increased expression of inflammatory genes 925:966 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 8 49 theme cultured 1118:1125 arg1 adipocytes 1127:1136 primary cultured adipocytes 1110:1136 primary cultured adipocytes 1110:1136 Both in primary cultured adipocytes and 3T3-L1 adipocytes treated with Ogt inhibitor showed increased secretion of free fatty acids. 37224467 7 50 theme cultured 1019:1026 arg1 adipocytes 1028:1037 Primary cultured adipocytes 1011:1037 Primary cultured adipocytes derived from Ogt-FKO mice 1011:1063 Primary cultured adipocytes derived from Ogt-FKO mice showed decreased lipid accumulation. 37224467 1 51 theme excess 127:132 arg1 energy 134:139 excess energy 127:139 excess energy 127:139 Adipose tissues accumulate excess energy as fat and heavily influence metabolic homeostasis. 37224467 3 52 theme O-GlcNAcylation 410:424 arg1 role 402:405 the role 398:405 the role of O-GlcNAcylation in adipose tissues during bodyweight gain due to overnutrition 398:487 However, little is known about the role of O-GlcNAcylation in adipose tissues during bodyweight gain due to overnutrition. 37224467 10 53 from expansion 1514:1522 arg1 mice 1527:1530 mice 1527:1530 mice 1527:1530 In conclusion, O-GlcNAcylation is important for healthy adipose expansion in mice. 37224467 7 54 theme Ogt-FKO 1052:1058 arg1 mice 1060:1063 Ogt-FKO mice 1052:1063 Ogt-FKO mice 1052:1063 Primary cultured adipocytes derived from Ogt-FKO mice showed decreased lipid accumulation. 37224467 9 55 theme inflammatory 1283:1294 arg1 genes 1296:1300 inflammatory genes 1283:1300 inflammatory genes 1283:1300 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 10 56 theme adipose 1506:1512 arg1 expansion 1514:1522 healthy adipose expansion 1498:1522 healthy adipose expansion in mice 1498:1530 In conclusion, O-GlcNAcylation is important for healthy adipose expansion in mice. 37224467 6 57 theme Ogt-FKO 754:760 arg1 mice 762:765 Ogt-FKO mice 754:765 Ogt-FKO mice 754:765 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 11 58 theme excess 1592:1597 arg1 energy 1599:1604 excess energy 1592:1604 excess energy 1592:1604 Glucose flux into adipose tissues may be a signal to store excess energy as fat. 37224467 2 59 theme cellular 347:354 arg1 processes 356:364 multiple cellular processes 338:364 multiple cellular processes 338:364 O-GlcNAc modification (O-GlcNAcylation), which involves the addition of N-acetylglucosamine to proteins by O-GlcNAc transferase (Ogt), modulates multiple cellular processes. 37224467 11 60 theme Glucose 1533:1539 arg1 signal 1576:1581 a signal 1574:1581 a signal to store excess energy as fat 1574:1611 Glucose flux into adipose tissues may be a signal to store excess energy as fat. 37224467 11 60 theme Glucose 1533:1539 arg1 flux 1541:1544 Glucose flux 1533:1544 Glucose flux into adipose tissues 1533:1565 Glucose flux into adipose tissues may be a signal to store excess energy as fat. 37224467 9 61 theme adipose 1412:1418 arg1 inflammation 1420:1431 adipose inflammation 1412:1431 adipose inflammation 1412:1431 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 6 62 theme bodyweight 843:852 arg1 gain 854:857 their reduced bodyweight gain 829:857 their reduced bodyweight gain 829:857 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 2 63 theme multiple 338:345 arg1 processes 356:364 multiple cellular processes 338:364 multiple cellular processes 338:364 O-GlcNAc modification (O-GlcNAcylation), which involves the addition of N-acetylglucosamine to proteins by O-GlcNAc transferase (Ogt), modulates multiple cellular processes. 37224467 9 64 theme inflammation 1420:1431 arg1 communication 1357:1369 cell-to-cell communication 1344:1369 cell-to-cell communication via free fatty acids 1344:1390 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 9 64 theme inflammation 1420:1431 arg1 cause 1403:1407 a cause 1401:1407 a cause of adipose inflammation in Ogt-FKO mice 1401:1447 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 6 65 theme reduced 835:841 arg1 gain 854:857 their reduced bodyweight gain 829:857 their reduced bodyweight gain 829:857 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 2 66 theme N-acetylglucosamine 265:283 arg1 addition 253:260 the addition 249:260 the addition of N-acetylglucosamine to proteins 249:295 O-GlcNAc modification (O-GlcNAcylation), which involves the addition of N-acetylglucosamine to proteins by O-GlcNAc transferase (Ogt), modulates multiple cellular processes. 37224467 11 67 theme adipose 1551:1557 arg1 tissues 1559:1565 adipose tissues 1551:1565 adipose tissues 1551:1565 Glucose flux into adipose tissues may be a signal to store excess energy as fat. 37224467 8 68 theme 3T3-L1 1142:1147 arg1 adipocytes 1149:1158 3T3-L1 adipocytes 1142:1158 3T3-L1 adipocytes 1142:1158 Both in primary cultured adipocytes and 3T3-L1 adipocytes treated with Ogt inhibitor showed increased secretion of free fatty acids. 37224467 6 69 theme increased 925:933 arg1 expression 935:944 increased expression 925:944 increased expression of inflammatory genes 925:966 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 6 70 dep de 895:896 arg1 novo 898:901 novo 898:901 novo 898:901 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 9 71 theme cell-to-cell 1344:1355 arg1 cause 1403:1407 a cause 1401:1407 a cause of adipose inflammation in Ogt-FKO mice 1401:1447 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 9 71 theme cell-to-cell 1344:1355 arg1 communication 1357:1369 cell-to-cell communication 1344:1369 cell-to-cell communication via free fatty acids 1344:1390 Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. 37224467 6 72 theme inflammatory 949:960 arg1 genes 962:966 inflammatory genes 949:966 inflammatory genes 949:966 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 37224467 6 73 theme age 1006:1008 arg1 weeks 997:1001 24 weeks 994:1001 24 weeks of age 994:1008 Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced bodyweight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. 36857743 2 0 link 1,3-dione-derived 377:393 arg1 enamines 395:402 1,3-dione-derived enamines 377:402 1,3-dione-derived enamines 377:402 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 0 1 theme N-N 122:124 arg1 Axis 126:129 a Chiral N-N Axis 113:129 a Chiral N-N Axis 113:129 Chiral Acid-Catalyzed Atroposelective Indolization Enables Access to 1,1'-Indole-Pyrroles and Bisindoles Bearing a Chiral N-N Axis. 36857743 2 2 from yield 494:498 arg1 ee 558:559 up to 92% ee 548:559 up to 92% ee 548:559 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 0 3 theme Chiral 115:120 arg1 Axis 126:129 a Chiral N-N Axis 113:129 a Chiral N-N Axis 113:129 Chiral Acid-Catalyzed Atroposelective Indolization Enables Access to 1,1'-Indole-Pyrroles and Bisindoles Bearing a Chiral N-N Axis. 36857743 2 4 theme acid 318:321 arg1 catalysis 287:295 the cooperative catalysis 271:295 the cooperative catalysis of chiral phosphoric acid and InBr3 271:331 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 5 dep ee 558:559 arg1 % 556:556 % 556:556 % 556:556 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 6 with 1,1'-pyrrole-indoles 458:477 arg1 yield 494:498 up to 92% yield 484:498 up to 92% yield 484:498 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 6 with 1,1'-pyrrole-indoles 458:477 arg1 bisindoles 534:543 bisindoles 534:543 bisindoles in up to 92% ee 534:559 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 6 with 1,1'-pyrrole-indoles 458:477 arg1 ee 526:527 ee 526:527 ee 526:527 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 6 with 1,1'-pyrrole-indoles 458:477 arg1 excess 518:523 94% enantiomeric excess 501:523 94% enantiomeric excess (ee) 501:528 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 7 dep % 492:492 arg1 92 490:491 92 490:491 92 490:491 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 8 theme phosphoric 307:316 arg1 acid 318:321 chiral phosphoric acid 300:321 chiral phosphoric acid 300:321 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 3 9 link linked 627:632 arg1 biheteroaryls 649:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 Derivatizations of these compounds to diverse functionalized N-N linked axially chiral biheteroaryls have also been demonstrated. 36857743 2 10 dep % 556:556 arg1 92 554:555 92 554:555 92 554:555 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 11 from excess 518:523 arg1 ee 558:559 up to 92% ee 548:559 up to 92% ee 548:559 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 12 dep 92 490:491 arg1 to 487:488 to 487:488 to 487:488 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 13 theme chiral 300:305 arg1 acid 318:321 chiral phosphoric acid 300:321 chiral phosphoric acid 300:321 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 1 14 theme efficient 196:204 arg1 synthesis 206:214 the efficient synthesis 192:214 the efficient synthesis of 1,1'-biheteroaryls bearing a chiral N-N axis 192:262 We present herein a highly atroposelective indolization for the efficient synthesis of 1,1'-biheteroaryls bearing a chiral N-N axis. 36857743 0 15 theme Acid-Catalyzed 7:20 arg1 Indolization 38:49 Chiral Acid-Catalyzed Atroposelective Indolization 0:49 Chiral Acid-Catalyzed Atroposelective Indolization 0:49 Chiral Acid-Catalyzed Atroposelective Indolization Enables Access to 1,1'-Indole-Pyrroles and Bisindoles Bearing a Chiral N-N Axis. 36857743 2 16 theme enantioselective 425:440 arg1 construction 442:453 a highly enantioselective construction 416:453 a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee 416:559 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 0 17 theme Chiral 0:5 arg1 Indolization 38:49 Chiral Acid-Catalyzed Atroposelective Indolization 0:49 Chiral Acid-Catalyzed Atroposelective Indolization 0:49 Chiral Acid-Catalyzed Atroposelective Indolization Enables Access to 1,1'-Indole-Pyrroles and Bisindoles Bearing a Chiral N-N Axis. 36857743 2 18 dep yield 494:498 arg1 % 492:492 % 492:492 % 492:492 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 3 19 theme N-N 623:625 arg1 biheteroaryls 649:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 Derivatizations of these compounds to diverse functionalized N-N linked axially chiral biheteroaryls have also been demonstrated. 36857743 1 20 theme 1,1'-biheteroaryls 219:236 arg1 synthesis 206:214 the efficient synthesis 192:214 the efficient synthesis of 1,1'-biheteroaryls bearing a chiral N-N axis 192:262 We present herein a highly atroposelective indolization for the efficient synthesis of 1,1'-biheteroaryls bearing a chiral N-N axis. 36857743 0 21 theme Atroposelective 22:36 arg1 Indolization 38:49 Chiral Acid-Catalyzed Atroposelective Indolization 0:49 Chiral Acid-Catalyzed Atroposelective Indolization 0:49 Chiral Acid-Catalyzed Atroposelective Indolization Enables Access to 1,1'-Indole-Pyrroles and Bisindoles Bearing a Chiral N-N Axis. 36857743 2 22 theme InBr3 327:331 arg1 catalysis 287:295 the cooperative catalysis 271:295 the cooperative catalysis of chiral phosphoric acid and InBr3 271:331 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 3 23 theme diverse 600:606 arg1 biheteroaryls 649:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 Derivatizations of these compounds to diverse functionalized N-N linked axially chiral biheteroaryls have also been demonstrated. 36857743 2 24 theme enantiomeric 505:516 arg1 ee 526:527 ee 526:527 ee 526:527 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 24 theme enantiomeric 505:516 arg1 excess 518:523 94% enantiomeric excess 501:523 94% enantiomeric excess (ee) 501:528 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 3 25 theme functionalized 608:621 arg1 biheteroaryls 649:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 Derivatizations of these compounds to diverse functionalized N-N linked axially chiral biheteroaryls have also been demonstrated. 36857743 2 26 theme 1,1'-pyrrole-indoles 458:477 arg1 construction 442:453 a highly enantioselective construction 416:453 a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee 416:559 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 27 theme % 503:503 arg1 ee 526:527 ee 526:527 ee 526:527 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 27 theme % 503:503 arg1 excess 518:523 94% enantiomeric excess 501:523 94% enantiomeric excess (ee) 501:528 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 28 dep 92 554:555 arg1 to 551:552 to 551:552 to 551:552 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 3 29 theme compounds 587:595 arg1 Derivatizations 562:576 Derivatizations 562:576 Derivatizations of these compounds to diverse functionalized N-N linked axially chiral biheteroaryls 562:661 Derivatizations of these compounds to diverse functionalized N-N linked axially chiral biheteroaryls have also been demonstrated. 36857743 2 30 theme 1,3-dione-derived 377:393 arg1 enamines 395:402 1,3-dione-derived enamines 377:402 1,3-dione-derived enamines 377:402 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 31 theme 94 501:502 arg1 % 503:503 % 503:503 % 503:503 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 2 32 from bisindoles 534:543 arg1 ee 558:559 up to 92% ee 548:559 up to 92% ee 548:559 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 1 33 theme N-N 255:257 arg1 axis 259:262 a chiral N-N axis 246:262 a chiral N-N axis 246:262 We present herein a highly atroposelective indolization for the efficient synthesis of 1,1'-biheteroaryls bearing a chiral N-N axis. 36857743 3 34 theme chiral 642:647 arg1 biheteroaryls 649:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 Derivatizations of these compounds to diverse functionalized N-N linked axially chiral biheteroaryls have also been demonstrated. 36857743 1 35 theme chiral 248:253 arg1 axis 259:262 a chiral N-N axis 246:262 a chiral N-N axis 246:262 We present herein a highly atroposelective indolization for the efficient synthesis of 1,1'-biheteroaryls bearing a chiral N-N axis. 36857743 2 36 theme cooperative 275:285 arg1 catalysis 287:295 the cooperative catalysis 271:295 the cooperative catalysis of chiral phosphoric acid and InBr3 271:331 Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. 36857743 3 37 theme linked 627:632 arg1 biheteroaryls 649:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 diverse functionalized N-N linked axially chiral biheteroaryls 600:661 Derivatizations of these compounds to diverse functionalized N-N linked axially chiral biheteroaryls have also been demonstrated. 36857743 1 38 theme atroposelective 159:173 arg1 indolization 175:186 a highly atroposelective indolization 150:186 a highly atroposelective indolization for the efficient synthesis of 1,1'-biheteroaryls bearing a chiral N-N axis 150:262 We present herein a highly atroposelective indolization for the efficient synthesis of 1,1'-biheteroaryls bearing a chiral N-N axis. 36349218 2 0 theme N-linked 431:438 arg1 glycosylation 440:452 N-linked glycosylation 431:452 N-linked glycosylation of coronavirus glycoproteins 431:481 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 3 1 theme envelope 640:647 arg1 protein 649:655 envelope protein 640:655 envelope protein 640:655 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 9 2 theme weakest 1118:1124 arg1 affinities 1126:1135 the weakest affinities 1114:1135 the weakest affinities 1114:1135 ORF7a had the weakest affinities. 36349218 6 3 theme viral 872:876 arg1 proteins 878:885 viral proteins 872:885 viral proteins with various degrees of affinity 872:918 Results TM can bind to viral proteins with various degrees of affinity. 36349218 3 4 gly glycoprotein 681:692 arg1 glycoprotein 681:692 spike glycoprotein 675:692 spike glycoprotein 675:692 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 1 5 theme several 217:223 arg1 vaccines 234:241 several COVID-19 vaccines 217:241 several COVID-19 vaccines 217:241 Introduction Despite the availability of several COVID-19 vaccines, the incidence of infections remains a serious issue. 36349218 1 6 theme COVID-19 225:232 arg1 vaccines 234:241 several COVID-19 vaccines 217:241 several COVID-19 vaccines 217:241 Introduction Despite the availability of several COVID-19 vaccines, the incidence of infections remains a serious issue. 36349218 2 7 theme glycoproteins 469:481 arg1 glycosylation 440:452 N-linked glycosylation 431:452 N-linked glycosylation of coronavirus glycoproteins 431:481 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 8 8 theme docking 1095:1101 arg1 degree 1085:1090 the degree 1081:1090 the degree of docking 1081:1101 Proteins (ORF9b, ORF8, nsp9, and RBD) were affected by unfavorable donor or acceptor bonds that impact the degree of docking. 36349218 8 9 theme unfavorable 1033:1043 arg1 donor 1045:1049 unfavorable donor or acceptor bonds 1033:1067 donor 1045:1049 Proteins (ORF9b, ORF8, nsp9, and RBD) were affected by unfavorable donor or acceptor bonds that impact the degree of docking. 36349218 2 10 theme coronavirus 457:467 arg1 glycoproteins 469:481 coronavirus glycoproteins 457:481 coronavirus glycoproteins 457:481 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 8 11 theme acceptor 1054:1061 arg1 bonds 1063:1067 unfavorable donor or acceptor bonds 1033:1067 bonds 1063:1067 Proteins (ORF9b, ORF8, nsp9, and RBD) were affected by unfavorable donor or acceptor bonds that impact the degree of docking. 36349218 2 12 gly glycoproteins 469:481 arg1 glycoproteins 469:481 coronavirus glycoproteins 457:481 coronavirus glycoproteins 457:481 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 2 13 theme subunit 396:402 arg1 synthesis 406:414 coronavirus envelope glycoprotein subunit 2 synthesis 362:414 coronavirus envelope glycoprotein subunit 2 synthesis 362:414 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 0 14 theme glycoprotein 162:173 arg1 envelope 136:143 envelope 136:143 envelope 136:143 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 14 theme glycoprotein 162:173 arg1 nsp2 97:100 nsp2 97:100 nsp2 97:100 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 14 theme glycoprotein 162:173 arg1 ORF8 123:126 ORF8 123:126 ORF8 123:126 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 14 theme glycoprotein 162:173 arg1 RBD 149:151 RBD 149:151 RBD 149:151 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 14 theme glycoprotein 162:173 arg1 Proteinase 75:84 Proteinase 75:84 Proteinase 75:84 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 14 theme glycoprotein 162:173 arg1 nsp9 103:106 nsp9 103:106 nsp9 103:106 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 14 theme glycoprotein 162:173 arg1 ORF9b 129:133 ORF9b 129:133 ORF9b 129:133 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 14 theme glycoprotein 162:173 arg1 protease 87:94 protease 87:94 protease 87:94 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 2 15 gly glycosylation 440:452 arg1 glycoproteins 469:481 coronavirus glycoproteins 457:481 coronavirus glycoproteins 457:481 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 2 16 theme glycoprotein 383:394 arg1 synthesis 406:414 coronavirus envelope glycoprotein subunit 2 synthesis 362:414 coronavirus envelope glycoprotein subunit 2 synthesis 362:414 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 1 17 theme vaccines 234:241 arg1 availability 201:212 the availability 197:212 the availability of several COVID-19 vaccines 197:241 Introduction Despite the availability of several COVID-19 vaccines, the incidence of infections remains a serious issue. 36349218 0 18 theme spike 156:160 arg1 glycoprotein 162:173 spike glycoprotein 156:173 spike glycoprotein 156:173 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 3 19 dep proteins 575:582 arg1 proteinase 585:594 proteinase 585:594 proteinase 585:594 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 0 20 theme affinity 25:32 arg1 Determination 0:12 Determination 0:12 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 0:174 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 3 21 theme spike 675:679 arg1 glycoprotein 681:692 spike glycoprotein 675:692 spike glycoprotein 675:692 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 7 22 theme highest 944:950 arg1 affinity 960:967 the highest binding affinity 940:967 the highest binding affinity 940:967 The proteinase had the highest binding affinity with TM. 36349218 4 23 theme bioinformatics 732:745 arg1 tools 747:751 bioinformatics tools 732:751 bioinformatics tools 732:751 Methods: Several types of chemo and bioinformatics tools were used to achieve the aim of the study. 36349218 7 24 contain had 936:938 arg2 affinity 960:967 the highest binding affinity 940:967 the highest binding affinity 940:967 The proteinase had the highest binding affinity with TM. 36349218 7 24 contain had 936:938 arg1 proteinase 925:934 The proteinase 921:934 The proteinase 921:934 The proteinase had the highest binding affinity with TM. 36349218 2 25 theme coronavirus 362:372 arg1 glycoprotein 383:394 coronavirus envelope glycoprotein 362:394 coronavirus envelope glycoprotein subunit 2 synthesis 362:414 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 6 26 theme Results 849:855 arg1 TM 857:858 Results TM 849:858 Results TM 849:858 Results TM can bind to viral proteins with various degrees of affinity. 36349218 7 27 theme binding 952:958 arg1 affinity 960:967 the highest binding affinity 940:967 the highest binding affinity 940:967 The proteinase had the highest binding affinity with TM. 36349218 3 28 dep Objectives 484:493 arg1 aimed 505:509 aimed 505:509 aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein) 505:693 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 29 dep proteinase 585:594 arg1 nsp2 658:661 nsp2 658:661 nsp2 658:661 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 29 dep proteinase 585:594 arg1 nsp9 607:610 nsp9 607:610 nsp9 607:610 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 29 dep proteinase 585:594 arg1 ORF7a 613:617 ORF7a 613:617 ORF7a 613:617 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 29 dep proteinase 585:594 arg1 ORF8 634:637 ORF8 634:637 ORF8 634:637 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 29 dep proteinase 585:594 arg1 RBD 668:670 RBD 668:670 RBD 668:670 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 29 dep proteinase 585:594 arg1 protease 597:604 protease 597:604 protease 597:604 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 29 dep proteinase 585:594 arg1 ORF3a 620:624 ORF3a 620:624 ORF3a 620:624 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 29 dep proteinase 585:594 arg1 protein 649:655 envelope protein 640:655 envelope protein 640:655 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 29 dep proteinase 585:594 arg1 ORF9b 627:631 ORF9b 627:631 ORF9b 627:631 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 0 30 theme tunicamycin 37:47 arg1 affinity 25:32 binding affinity 17:32 binding affinity of tunicamycin with SARS-CoV-2 proteins 17:72 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 8 31 dep Proteins 978:985 arg1 nsp9 1001:1004 nsp9 1001:1004 nsp9 1001:1004 Proteins (ORF9b, ORF8, nsp9, and RBD) were affected by unfavorable donor or acceptor bonds that impact the degree of docking. 36349218 8 31 dep Proteins 978:985 arg1 RBD 1011:1013 RBD 1011:1013 RBD 1011:1013 Proteins (ORF9b, ORF8, nsp9, and RBD) were affected by unfavorable donor or acceptor bonds that impact the degree of docking. 36349218 8 31 dep Proteins 978:985 arg1 ORF8 995:998 ORF8 995:998 ORF8 995:998 Proteins (ORF9b, ORF8, nsp9, and RBD) were affected by unfavorable donor or acceptor bonds that impact the degree of docking. 36349218 8 31 dep Proteins 978:985 arg1 ORF9b 988:992 ORF9b 988:992 ORF9b 988:992 Proteins (ORF9b, ORF8, nsp9, and RBD) were affected by unfavorable donor or acceptor bonds that impact the degree of docking. 36349218 8 31 dep Proteins 978:985 arg1 Proteins 978:985 Proteins 978:985 Proteins (ORF9b, ORF8, nsp9, and RBD) 978:1014 Proteins (ORF9b, ORF8, nsp9, and RBD) were affected by unfavorable donor or acceptor bonds that impact the degree of docking. 36349218 3 32 theme coronavirus 563:573 arg1 proteins 575:582 certain coronavirus proteins 555:582 certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein) 555:693 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 10 33 from effect 1179:1184 arg1 SARS-CoV-2 1189:1198 SARS-CoV-2 1189:1198 SARS-CoV-2 1189:1198 Conclusions This antibiotic is likely to effect on SARS-CoV-2 in clinical studies. 36349218 10 33 from effect 1179:1184 arg1 studies 1212:1218 clinical studies 1203:1218 clinical studies 1203:1218 Conclusions This antibiotic is likely to effect on SARS-CoV-2 in clinical studies. 36349218 0 34 theme binding 17:23 arg1 affinity 25:32 binding affinity 17:32 binding affinity of tunicamycin with SARS-CoV-2 proteins 17:72 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 2 35 theme envelope 374:381 arg1 glycoprotein 383:394 coronavirus envelope glycoprotein 362:394 coronavirus envelope glycoprotein subunit 2 synthesis 362:414 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 2 36 link N-linked 431:438 arg1 glycosylation 440:452 N-linked glycosylation 431:452 N-linked glycosylation of coronavirus glycoproteins 431:481 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 0 37 gly glycoprotein 162:173 arg1 glycoprotein 162:173 spike glycoprotein 156:173 spike glycoprotein 156:173 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 38 theme SARS-CoV-2 54:63 arg1 proteins 65:72 SARS-CoV-2 proteins 54:72 SARS-CoV-2 proteins 54:72 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 1 39 theme infections 261:270 arg1 incidence 248:256 the incidence 244:256 the incidence of infections 244:270 Introduction Despite the availability of several COVID-19 vaccines, the incidence of infections remains a serious issue. 36349218 6 40 theme affinity 911:918 arg1 degrees 900:906 various degrees 892:906 various degrees of affinity 892:918 Results TM can bind to viral proteins with various degrees of affinity. 36349218 1 41 dep Introduction 176:187 arg1 availability 201:212 the availability 197:212 the availability of several COVID-19 vaccines 197:241 Introduction Despite the availability of several COVID-19 vaccines, the incidence of infections remains a serious issue. 36349218 4 42 theme tools 747:751 arg1 types 713:717 Several types 705:717 Several types of chemo and bioinformatics tools 705:751 Methods: Several types of chemo and bioinformatics tools were used to achieve the aim of the study. 36349218 10 43 dep Conclusions 1138:1148 arg1 likely 1169:1174 likely 1169:1174 likely 1169:1174 Conclusions This antibiotic is likely to effect on SARS-CoV-2 in clinical studies. 36349218 3 44 theme glycoprotein 681:692 arg1 nsp2 658:661 nsp2 658:661 nsp2 658:661 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 44 theme glycoprotein 681:692 arg1 nsp9 607:610 nsp9 607:610 nsp9 607:610 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 44 theme glycoprotein 681:692 arg1 ORF7a 613:617 ORF7a 613:617 ORF7a 613:617 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 44 theme glycoprotein 681:692 arg1 ORF8 634:637 ORF8 634:637 ORF8 634:637 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 44 theme glycoprotein 681:692 arg1 RBD 668:670 RBD 668:670 RBD 668:670 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 44 theme glycoprotein 681:692 arg1 protease 597:604 protease 597:604 protease 597:604 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 44 theme glycoprotein 681:692 arg1 ORF3a 620:624 ORF3a 620:624 ORF3a 620:624 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 44 theme glycoprotein 681:692 arg1 protein 649:655 envelope protein 640:655 envelope protein 640:655 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 3 44 theme glycoprotein 681:692 arg1 ORF9b 627:631 ORF9b 627:631 ORF9b 627:631 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 4 45 theme study 789:793 arg1 aim 778:780 the aim 774:780 the aim of the study 774:793 Methods: Several types of chemo and bioinformatics tools were used to achieve the aim of the study. 36349218 3 46 theme certain 555:561 arg1 proteins 575:582 certain coronavirus proteins 555:582 certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein) 555:693 Objectives Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). 36349218 4 47 used used 758:761 arg2 types 713:717 Several types 705:717 Several types of chemo and bioinformatics tools 705:751 Methods: Several types of chemo and bioinformatics tools were used to achieve the aim of the study. 36349218 4 48 theme Several 705:711 arg1 types 713:717 Several types 705:717 Several types of chemo and bioinformatics tools 705:751 Methods: Several types of chemo and bioinformatics tools were used to achieve the aim of the study. 36349218 2 49 gly glycoprotein 383:394 arg1 glycoprotein 383:394 coronavirus envelope glycoprotein 362:394 coronavirus envelope glycoprotein subunit 2 synthesis 362:414 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 4 50 theme chemo 722:726 arg1 types 713:717 Several types 705:717 Several types of chemo and bioinformatics tools 705:751 Methods: Several types of chemo and bioinformatics tools were used to achieve the aim of the study. 36349218 0 51 with affinity 25:32 arg1 proteins 65:72 SARS-CoV-2 proteins 54:72 SARS-CoV-2 proteins 54:72 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 2 52 theme tumor 340:344 arg1 growth 346:351 tumor growth 340:351 tumor growth 340:351 Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. 36349218 6 53 with proteins 878:885 arg1 degrees 900:906 various degrees 892:906 various degrees of affinity 892:918 Results TM can bind to viral proteins with various degrees of affinity. 36349218 10 54 theme clinical 1203:1210 arg1 studies 1212:1218 clinical studies 1203:1218 clinical studies 1203:1218 Conclusions This antibiotic is likely to effect on SARS-CoV-2 in clinical studies. 36349218 6 55 theme various 892:898 arg1 degrees 900:906 various degrees 892:906 various degrees of affinity 892:918 Results TM can bind to viral proteins with various degrees of affinity. 36349218 1 56 theme serious 282:288 arg1 issue 290:294 a serious issue 280:294 a serious issue 280:294 Introduction Despite the availability of several COVID-19 vaccines, the incidence of infections remains a serious issue. 36349218 0 57 dep Determination 0:12 arg1 envelope 136:143 envelope 136:143 envelope 136:143 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 57 dep Determination 0:12 arg1 nsp2 97:100 nsp2 97:100 nsp2 97:100 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 57 dep Determination 0:12 arg1 ORF7a 116:120 ORF7a 116:120 ORF7a 116:120 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 57 dep Determination 0:12 arg1 ORF8 123:126 ORF8 123:126 ORF8 123:126 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 57 dep Determination 0:12 arg1 RBD 149:151 RBD 149:151 RBD 149:151 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 57 dep Determination 0:12 arg1 Proteinase 75:84 Proteinase 75:84 Proteinase 75:84 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 57 dep Determination 0:12 arg1 nsp9 103:106 nsp9 103:106 nsp9 103:106 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 57 dep Determination 0:12 arg1 ORF9b 129:133 ORF9b 129:133 ORF9b 129:133 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 0 57 dep Determination 0:12 arg1 protease 87:94 protease 87:94 protease 87:94 Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein. 36349218 9 58 contain had 1110:1112 arg1 ORF7a 1104:1108 ORF7a 1104:1108 ORF7a 1104:1108 ORF7a had the weakest affinities. 36349218 9 58 contain had 1110:1112 arg2 affinities 1126:1135 the weakest affinities 1114:1135 the weakest affinities 1114:1135 ORF7a had the weakest affinities. 36501390 0 0 theme BYDV 99:102 arg1 Efficiency 117:126 BYDV Transmission Efficiency 99:126 BYDV Transmission Efficiency by Sitobion miscanthi 99:148 Proteomic and Transcriptomic Analysis for Identification of Endosymbiotic Bacteria Associated with BYDV Transmission Efficiency by Sitobion miscanthi. 36501390 8 1 theme aphid-virus 1584:1594 arg1 interactions 1596:1607 aphid-virus interactions 1584:1607 aphid-virus interactions 1584:1607 They should therefore be included in investigations into aphid-virus interactions and plant disease epidemiology. 36501390 2 2 theme BYDV 625:628 arg1 efficiency 643:652 BYDV transmission efficiency 625:652 BYDV transmission efficiency 625:652 Therefore, two aphids' geographic populations, differing in their BYDV transmission efficiency, after characterizing their endosymbionts, were treated with antibiotics to investigate how changes in the composition of their endosymbiont population affected BYDV transmission efficiency. 36501390 1 3 theme important 174:182 arg1 vector 190:195 an important viral vector 171:195 an important viral vector of barley yellow dwarf virus (BYDV) 171:231 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 1 3 theme important 174:182 arg1 miscanthi 160:168 Sitobion miscanthi 151:168 Sitobion miscanthi 151:168 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 5 4 theme STY 1235:1237 arg1 treatment 1250:1258 the STY ampicillin treatment 1231:1258 the STY ampicillin treatment 1231:1258 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 3 5 theme geographic 718:727 arg1 populations 729:739 two geographic populations 714:739 two geographic populations 714:739 After antibiotic treatment, Rickettsia was eliminated from two geographic populations. 36501390 6 6 theme nascent 1325:1331 arg1 complex 1356:1362 nascent polypeptide-associated complex subunit alpha and proteasome 1325:1391 nascent polypeptide-associated complex subunit alpha and proteasome 1325:1391 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 6 6 theme nascent 1325:1331 arg1 symL 1319:1322 symbionin symL 1309:1322 symbionin symL 1309:1322 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 1 7 theme viral 184:188 arg1 vector 190:195 an important viral vector 171:195 an important viral vector of barley yellow dwarf virus (BYDV) 171:231 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 1 7 theme viral 184:188 arg1 miscanthi 160:168 Sitobion miscanthi 151:168 Sitobion miscanthi 151:168 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 5 8 theme ampicillin 1239:1248 arg1 treatment 1250:1258 the STY ampicillin treatment 1231:1258 the STY ampicillin treatment 1231:1258 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 2 9 theme population 605:614 arg1 composition 571:581 the composition 567:581 the composition of their endosymbiont population 567:614 Therefore, two aphids' geographic populations, differing in their BYDV transmission efficiency, after characterizing their endosymbionts, were treated with antibiotics to investigate how changes in the composition of their endosymbiont population affected BYDV transmission efficiency. 36501390 0 10 theme Transmission 104:115 arg1 Efficiency 117:126 BYDV Transmission Efficiency 99:126 BYDV Transmission Efficiency by Sitobion miscanthi 99:148 Proteomic and Transcriptomic Analysis for Identification of Endosymbiotic Bacteria Associated with BYDV Transmission Efficiency by Sitobion miscanthi. 36501390 5 11 theme STY 1127:1129 arg1 treatment 1142:1150 the STY rifampicin treatment 1123:1150 the STY rifampicin treatment 1123:1150 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 2 12 theme endosymbiont 592:603 arg1 population 605:614 their endosymbiont population 586:614 their endosymbiont population 586:614 Therefore, two aphids' geographic populations, differing in their BYDV transmission efficiency, after characterizing their endosymbionts, were treated with antibiotics to investigate how changes in the composition of their endosymbiont population affected BYDV transmission efficiency. 36501390 6 13 theme symL 1319:1322 arg1 abundance 1296:1304 the abundance 1292:1304 the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome 1292:1391 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 4 14 theme BYDV 742:745 arg1 efficiency 760:769 BYDV transmission efficiency 742:769 BYDV transmission efficiency by STY geographic population 742:798 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 0 15 theme Sitobion 131:138 arg1 miscanthi 140:148 Sitobion miscanthi 131:148 Sitobion miscanthi 131:148 Proteomic and Transcriptomic Analysis for Identification of Endosymbiotic Bacteria Associated with BYDV Transmission Efficiency by Sitobion miscanthi. 36501390 5 16 theme rifampicin 1131:1140 arg1 treatment 1142:1150 the STY rifampicin treatment 1123:1150 the STY rifampicin treatment 1123:1150 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 4 17 theme HDZ 882:884 arg1 population 897:906 HDZ geographic population 882:906 HDZ geographic population 882:906 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 7 18 theme vector 1500:1505 arg1 transmission 1513:1524 vector viral transmission 1500:1524 vector viral transmission 1500:1524 We found that the endosymbionts can mediate vector viral transmission. 36501390 0 19 theme Proteomic 0:8 arg1 Analysis 29:36 Proteomic and Transcriptomic Analysis 0:36 Proteomic and Transcriptomic Analysis for Identification of Endosymbiotic Bacteria 0:81 Proteomic and Transcriptomic Analysis for Identification of Endosymbiotic Bacteria Associated with BYDV Transmission Efficiency by Sitobion miscanthi. 36501390 4 20 with % 958:958 arg1 ampicillin 938:947 ampicillin 938:947 ampicillin 938:947 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 4 20 with % 958:958 arg1 rifampicin 965:974 rifampicin 965:974 rifampicin 965:974 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 2 21 theme transmission 440:451 arg1 efficiency 453:462 their BYDV transmission efficiency 429:462 their BYDV transmission efficiency 429:462 Therefore, two aphids' geographic populations, differing in their BYDV transmission efficiency, after characterizing their endosymbionts, were treated with antibiotics to investigate how changes in the composition of their endosymbiont population affected BYDV transmission efficiency. 36501390 6 22 theme polypeptide-associated 1333:1354 arg1 complex 1356:1362 nascent polypeptide-associated complex subunit alpha and proteasome 1325:1391 nascent polypeptide-associated complex subunit alpha and proteasome 1325:1391 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 6 22 theme polypeptide-associated 1333:1354 arg1 symL 1319:1322 symbionin symL 1309:1322 symbionin symL 1309:1322 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 8 23 theme disease 1619:1625 arg1 epidemiology 1627:1638 plant disease epidemiology 1613:1638 plant disease epidemiology 1613:1638 They should therefore be included in investigations into aphid-virus interactions and plant disease epidemiology. 36501390 1 24 theme barley 200:205 arg1 virus 220:224 barley yellow dwarf virus 200:224 barley yellow dwarf virus (BYDV) 200:231 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 1 24 theme barley 200:205 arg1 BYDV 227:230 BYDV 227:230 BYDV 227:230 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 2 25 theme BYDV 435:438 arg1 efficiency 453:462 their BYDV transmission efficiency 429:462 their BYDV transmission efficiency 429:462 Therefore, two aphids' geographic populations, differing in their BYDV transmission efficiency, after characterizing their endosymbionts, were treated with antibiotics to investigate how changes in the composition of their endosymbiont population affected BYDV transmission efficiency. 36501390 4 26 with % 831:831 arg1 rifampicin 866:875 rifampicin 866:875 rifampicin 866:875 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 4 26 with % 831:831 arg1 ampicillin 838:847 ampicillin 838:847 ampicillin 838:847 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 2 27 theme transmission 630:641 arg1 efficiency 643:652 BYDV transmission efficiency 625:652 BYDV transmission efficiency 625:652 Therefore, two aphids' geographic populations, differing in their BYDV transmission efficiency, after characterizing their endosymbionts, were treated with antibiotics to investigate how changes in the composition of their endosymbiont population affected BYDV transmission efficiency. 36501390 4 28 theme geographic 778:787 arg1 population 789:798 STY geographic population 774:798 STY geographic population 774:798 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 1 29 theme yellow 207:212 arg1 virus 220:224 barley yellow dwarf virus 200:224 barley yellow dwarf virus (BYDV) 200:231 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 1 29 theme yellow 207:212 arg1 BYDV 227:230 BYDV 227:230 BYDV 227:230 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 6 30 theme Proteomic 1261:1269 arg1 analysis 1271:1278 Proteomic analysis 1261:1278 Proteomic analysis 1261:1278 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 6 31 dep complex 1356:1362 arg1 alpha 1372:1376 subunit alpha 1364:1376 subunit alpha 1364:1376 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 6 31 dep complex 1356:1362 arg1 proteasome 1382:1391 proteasome 1382:1391 proteasome 1382:1391 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 1 32 theme dwarf 214:218 arg1 virus 220:224 barley yellow dwarf virus 200:224 barley yellow dwarf virus (BYDV) 200:231 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 1 32 theme dwarf 214:218 arg1 BYDV 227:230 BYDV 227:230 BYDV 227:230 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 0 33 theme Transcriptomic 14:27 arg1 Analysis 29:36 Proteomic and Transcriptomic Analysis 0:36 Proteomic and Transcriptomic Analysis for Identification of Endosymbiotic Bacteria 0:81 Proteomic and Transcriptomic Analysis for Identification of Endosymbiotic Bacteria Associated with BYDV Transmission Efficiency by Sitobion miscanthi. 36501390 5 34 theme Transcriptomic 977:990 arg1 analysis 992:999 Transcriptomic analysis 977:999 Transcriptomic analysis 977:999 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 1 35 theme virus 220:224 arg1 vector 190:195 an important viral vector 171:195 an important viral vector of barley yellow dwarf virus (BYDV) 171:231 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 1 35 theme virus 220:224 arg1 miscanthi 160:168 Sitobion miscanthi 151:168 Sitobion miscanthi 151:168 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 5 36 theme immune 1047:1052 arg1 system 1054:1059 the immune system 1043:1059 the immune system 1043:1059 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 4 37 with % 931:931 arg1 ampicillin 938:947 ampicillin 938:947 ampicillin 938:947 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 4 37 with % 931:931 arg1 rifampicin 965:974 rifampicin 965:974 rifampicin 965:974 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 3 38 theme antibiotic 661:670 arg1 treatment 672:680 antibiotic treatment 661:680 antibiotic treatment 661:680 After antibiotic treatment, Rickettsia was eliminated from two geographic populations. 36501390 2 39 theme geographic 392:401 arg1 populations 403:413 two aphids' geographic populations 380:413 two aphids' geographic populations 380:413 Therefore, two aphids' geographic populations, differing in their BYDV transmission efficiency, after characterizing their endosymbionts, were treated with antibiotics to investigate how changes in the composition of their endosymbiont population affected BYDV transmission efficiency. 36501390 0 40 theme Endosymbiotic 60:72 arg1 Bacteria 74:81 Endosymbiotic Bacteria 60:81 Endosymbiotic Bacteria 60:81 Proteomic and Transcriptomic Analysis for Identification of Endosymbiotic Bacteria Associated with BYDV Transmission Efficiency by Sitobion miscanthi. 36501390 5 41 theme glycan 1183:1188 arg1 biosynthesis 1190:1201 glycan biosynthesis 1183:1201 glycan biosynthesis 1183:1201 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 6 42 theme symbionin 1309:1317 arg1 complex 1356:1362 nascent polypeptide-associated complex subunit alpha and proteasome 1325:1391 nascent polypeptide-associated complex subunit alpha and proteasome 1325:1391 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 6 42 theme symbionin 1309:1317 arg1 symL 1319:1322 symbionin symL 1309:1322 symbionin symL 1309:1322 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 4 43 theme geographic 886:895 arg1 population 897:906 HDZ geographic population 882:906 HDZ geographic population 882:906 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 5 44 theme carbohydrate 1062:1073 arg1 metabolism 1075:1084 carbohydrate metabolism 1062:1084 carbohydrate metabolism 1062:1084 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 5 44 theme carbohydrate 1062:1073 arg1 DEGs 1027:1030 DEGs 1027:1030 DEGs related to the immune system 1027:1059 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 4 45 theme transmission 747:758 arg1 efficiency 760:769 BYDV transmission efficiency 742:769 BYDV transmission efficiency by STY geographic population 742:798 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 6 46 theme subunit 1364:1370 arg1 alpha 1372:1376 subunit alpha 1364:1376 subunit alpha 1364:1376 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 5 47 theme DEGs 1027:1030 arg1 number 1017:1022 the number 1013:1022 the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism 1013:1105 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 1 48 theme Sitobion 151:158 arg1 vector 190:195 an important viral vector 171:195 an important viral vector of barley yellow dwarf virus (BYDV) 171:231 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 1 48 theme Sitobion 151:158 arg1 miscanthi 160:168 Sitobion miscanthi 151:168 Sitobion miscanthi 151:168 Sitobion miscanthi, an important viral vector of barley yellow dwarf virus (BYDV), is also symbiotically associated with endosymbionts, but little is known about the interactions between endosymbionts, aphid and BYDV. 36501390 7 49 theme viral 1507:1511 arg1 transmission 1513:1524 vector viral transmission 1500:1524 vector viral transmission 1500:1524 We found that the endosymbionts can mediate vector viral transmission. 36501390 5 50 theme lipid 1090:1094 arg1 DEGs 1027:1030 DEGs 1027:1030 DEGs related to the immune system 1027:1059 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 5 50 theme lipid 1090:1094 arg1 metabolism 1096:1105 lipid metabolism 1090:1105 lipid metabolism 1090:1105 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 5 51 theme related 1032:1038 arg1 DEGs 1027:1030 DEGs 1027:1030 DEGs related to the immune system 1027:1059 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 5 51 theme related 1032:1038 arg1 metabolism 1096:1105 lipid metabolism 1090:1105 lipid metabolism 1090:1105 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 5 51 theme related 1032:1038 arg1 metabolism 1075:1084 carbohydrate metabolism 1062:1084 carbohydrate metabolism 1062:1084 Transcriptomic analysis showed that the number of DEGs related to the immune system, carbohydrate metabolism and lipid metabolism did increase in the STY rifampicin treatment, while replication and repair, glycan biosynthesis and metabolism increased in the STY ampicillin treatment. 36501390 6 52 theme geographic 1432:1441 arg1 populations 1443:1453 the two geographic populations 1424:1453 the two geographic populations 1424:1453 Proteomic analysis showed that the abundance of symbionin symL, nascent polypeptide-associated complex subunit alpha and proteasome differed significantly between the two geographic populations. 36501390 4 53 theme STY 774:776 arg1 population 789:798 STY geographic population 774:798 STY geographic population 774:798 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 8 54 theme plant 1613:1617 arg1 epidemiology 1627:1638 plant disease epidemiology 1613:1638 plant disease epidemiology 1613:1638 They should therefore be included in investigations into aphid-virus interactions and plant disease epidemiology. 36501390 9 55 theme strategies 1695:1704 arg1 development 1680:1690 the development 1676:1690 the development of strategies 1676:1704 Our findings should also help with the development of strategies to prevent virus transmission. 36501390 0 56 theme Bacteria 74:81 arg1 Identification 42:55 Identification 42:55 Identification of Endosymbiotic Bacteria 42:81 Proteomic and Transcriptomic Analysis for Identification of Endosymbiotic Bacteria Associated with BYDV Transmission Efficiency by Sitobion miscanthi. 36501390 4 57 with % 859:859 arg1 rifampicin 866:875 rifampicin 866:875 rifampicin 866:875 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 4 57 with % 859:859 arg1 ampicillin 838:847 ampicillin 838:847 ampicillin 838:847 BYDV transmission efficiency by STY geographic population dropped significantly, by -44.2% with ampicillin and -25.01% with rifampicin, but HDZ geographic population decreased by only 14.19% with ampicillin and 23.88% with rifampicin. 36501390 9 58 theme virus 1717:1721 arg1 transmission 1723:1734 virus transmission 1717:1734 virus transmission 1717:1734 Our findings should also help with the development of strategies to prevent virus transmission. 36501390 2 59 from changes 556:562 arg1 composition 571:581 the composition 567:581 the composition of their endosymbiont population 567:614 Therefore, two aphids' geographic populations, differing in their BYDV transmission efficiency, after characterizing their endosymbionts, were treated with antibiotics to investigate how changes in the composition of their endosymbiont population affected BYDV transmission efficiency. 36498063 5 0 theme gut-microbe-related 676:694 arg1 comorbidities 696:708 gut-microbe-related comorbidities 676:708 gut-microbe-related comorbidities 676:708 Diversity, microbial composition, functional pathways, smoking history, and gut-microbe-related comorbidities were analyzed to assess the factors associated with the risk of NSCLC. 36498063 11 1 theme Bacteroides 1487:1497 arg1 caccae 1499:1504 Bacteroides caccae 1487:1504 Bacteroides caccae 1487:1504 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 2 2 theme non-small-cell 268:281 arg1 NSCLC 296:300 NSCLC 296:300 NSCLC 296:300 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 2 2 theme non-small-cell 268:281 arg1 cancer 288:293 treatment-naïve non-small-cell lung cancer 252:293 age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients 240:310 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 7 3 theme significant 1098:1108 arg1 differences 1110:1120 significant differences 1098:1120 significant differences between the patients and controls 1098:1154 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 11 4 theme steroid 1537:1543 arg1 biosynthesis 1553:1564 steroid hormone biosynthesis 1537:1564 steroid hormone biosynthesis (p < 0.001) 1537:1576 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 4 theme steroid 1537:1543 arg1 < 1569:1569 p < 0.001 1567:1575 p < 0.001 1567:1575 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 2 5 theme age-matched 240:250 arg1 patients 303:310 age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients 240:310 age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients 240:310 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 1 6 theme various 142:148 arg1 diseases 160:167 various malignant diseases 142:167 various malignant diseases 142:167 Background: The imbalance of gut microbiota, dysbiosis, is associated with various malignant diseases. 36498063 8 7 theme NSCLC 1258:1262 arg1 risk 1250:1253 an increased risk 1237:1253 an increased risk of NSCLC 1237:1262 and Bacteroides caccae was associated with an increased risk of NSCLC (p = 0.003 and 0.007, respectively). 36498063 11 8 theme p 1705:1705 arg1 peroxisome 1693:1702 peroxisome 1693:1702 peroxisome (p < 0.001) 1693:1714 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 8 theme p 1705:1705 arg1 < 1707:1707 p < 0.001 1705:1713 p < 0.001 1705:1713 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 5 9 theme smoking 655:661 arg1 history 663:669 smoking history 655:669 smoking history 655:669 Diversity, microbial composition, functional pathways, smoking history, and gut-microbe-related comorbidities were analyzed to assess the factors associated with the risk of NSCLC. 36498063 6 10 theme alpha 800:804 arg1 diversity 806:814 Microbial alpha diversity 790:814 Microbial alpha diversity 790:814 Results: Microbial alpha diversity was decreased in the patients with NSCLC, and beta diversity was significantly different between the patients and controls (p < 0.001). 36498063 17 11 theme NSCLC 2346:2350 arg1 development 2331:2341 the development 2327:2341 the development of NSCLC 2327:2350 Further investigations on the mechanism underlying the potential association between gut dysbiosis and the development of NSCLC are warranted. 36498063 17 11 theme NSCLC 2346:2350 arg1 investigations 2232:2245 Further investigations 2224:2245 Further investigations on the mechanism underlying the potential association between gut dysbiosis 2224:2321 Further investigations on the mechanism underlying the potential association between gut dysbiosis and the development of NSCLC are warranted. 36498063 2 12 theme cancer 288:293 arg1 patients 303:310 age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients 240:310 age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients 240:310 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 7 13 theme diabetes 1010:1017 arg1 mellitus 1019:1026 diabetes mellitus 1010:1026 diabetes mellitus 1010:1026 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 7 14 theme pulmonary 1049:1057 arg1 disease 1059:1065 chronic obstructive pulmonary disease 1029:1065 chronic obstructive pulmonary disease 1029:1065 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 1 15 theme gut 96:98 arg1 microbiota 100:109 gut microbiota 96:109 gut microbiota 96:109 Background: The imbalance of gut microbiota, dysbiosis, is associated with various malignant diseases. 36498063 1 15 theme gut 96:98 arg1 dysbiosis 112:120 dysbiosis 112:120 dysbiosis 112:120 Background: The imbalance of gut microbiota, dysbiosis, is associated with various malignant diseases. 36498063 7 16 with sex 974:976 arg1 differences 1110:1120 significant differences 1098:1120 significant differences between the patients and controls 1098:1154 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 7 17 theme chronic 1029:1035 arg1 disease 1059:1065 chronic obstructive pulmonary disease 1029:1065 chronic obstructive pulmonary disease 1029:1065 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 2 18 theme microbiota 226:235 arg1 characteristics 203:217 the characteristics 199:217 the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals 199:334 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 11 19 theme p 1794:1794 arg1 metabolism 1782:1791 glycerolipid metabolism 1769:1791 glycerolipid metabolism (p < 0.001) 1769:1803 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 19 theme p 1794:1794 arg1 < 1796:1796 p < 0.001 1794:1802 p < 0.001 1794:1802 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 20 theme acid 1664:1667 arg1 0.039 1685:1689 p = 0.039 1681:1689 p = 0.039 1681:1689 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 20 theme acid 1664:1667 arg1 metabolism 1669:1678 lipoic acid metabolism 1657:1678 lipoic acid metabolism (p = 0.039) 1657:1690 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 0 21 theme Non-Small-Cell 39:52 arg1 Cancer 59:64 Non-Small-Cell Lung Cancer 39:64 Non-Small-Cell Lung Cancer 39:64 Impact of Gut Dysbiosis on the Risk of Non-Small-Cell Lung Cancer. 36498063 14 22 theme Anaerotruncus 1984:1996 arg1 spp 1998:2000 Bacteroides caccae or Anaerotruncus spp 1962:2000 spp 1998:2000 No overlapping signaling pathways were modulated by Bacteroides caccae or Anaerotruncus spp. 36498063 0 23 theme Cancer 59:64 arg1 Risk 31:34 the Risk 27:34 the Risk of Non-Small-Cell Lung Cancer 27:64 Impact of Gut Dysbiosis on the Risk of Non-Small-Cell Lung Cancer. 36498063 0 24 from Impact 0:5 arg1 Risk 31:34 the Risk 27:34 the Risk of Non-Small-Cell Lung Cancer 27:64 Impact of Gut Dysbiosis on the Risk of Non-Small-Cell Lung Cancer. 36498063 16 25 theme smoking 2168:2174 arg1 history 2176:2182 smoking history 2168:2182 smoking history 2168:2182 and Bacteroides caccae were abundant and may be associated with the risk of NSCLC regardless of sex, smoking history, and gut-microbe-related comorbidities. 36498063 11 26 theme = 1683:1683 arg1 0.039 1685:1689 p = 0.039 1681:1689 p = 0.039 1681:1689 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 26 theme = 1683:1683 arg1 metabolism 1669:1678 lipoic acid metabolism 1657:1678 lipoic acid metabolism (p = 0.039) 1657:1690 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 13 27 dep only 1892:1895 arg1 p 1898:1898 p = 0.001 1898:1906 p = 0.001 1898:1906 was positively associated with decreased biosynthesis of ansamycin only (p = 0.001). 36498063 7 28 with mellitus 1019:1026 arg1 differences 1110:1120 significant differences 1098:1120 significant differences between the patients and controls 1098:1154 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 10 29 theme < 1447:1447 arg1 p 1445:1445 both p < 0.001 1440:1453 both p < 0.001 1440:1453 and Bacteroides caccae, respectively (both p < 0.001). 36498063 17 30 from investigations 2232:2245 arg1 mechanism 2254:2262 the mechanism 2250:2262 the mechanism underlying the potential association between gut dysbiosis 2250:2321 Further investigations on the mechanism underlying the potential association between gut dysbiosis and the development of NSCLC are warranted. 36498063 2 31 from characteristics 203:217 arg1 patients 303:310 age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients 240:310 age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients 240:310 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 2 31 from characteristics 203:217 arg1 individuals 324:334 healthy individuals 316:334 healthy individuals 316:334 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 0 32 theme Lung 54:57 arg1 Cancer 59:64 Non-Small-Cell Lung Cancer 39:64 Non-Small-Cell Lung Cancer 39:64 Impact of Gut Dysbiosis on the Risk of Non-Small-Cell Lung Cancer. 36498063 14 33 theme signaling 1925:1933 arg1 pathways 1935:1942 No overlapping signaling pathways 1910:1942 No overlapping signaling pathways 1910:1942 No overlapping signaling pathways were modulated by Bacteroides caccae or Anaerotruncus spp. 36498063 16 34 theme gut-microbe-related 2189:2207 arg1 comorbidities 2209:2221 gut-microbe-related comorbidities 2189:2221 gut-microbe-related comorbidities 2189:2221 and Bacteroides caccae were abundant and may be associated with the risk of NSCLC regardless of sex, smoking history, and gut-microbe-related comorbidities. 36498063 3 35 theme NSCLC 463:467 arg1 patients 469:476 34 age-matched NSCLC patients 448:476 34 age-matched NSCLC patients 448:476 Methods: We enrolled 34 age-matched NSCLC patients and 268 healthy individuals. 36498063 0 36 theme Gut 10:12 arg1 Dysbiosis 14:22 Gut Dysbiosis 10:22 Gut Dysbiosis 10:22 Impact of Gut Dysbiosis on the Risk of Non-Small-Cell Lung Cancer. 36498063 4 37 theme fecal 570:574 arg1 samples 576:582 freshly collected fecal samples 552:582 freshly collected fecal samples 552:582 Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples were sequenced. 36498063 17 38 theme potential 2279:2287 arg1 association 2289:2299 the potential association 2275:2299 the potential association between gut dysbiosis 2275:2321 Further investigations on the mechanism underlying the potential association between gut dysbiosis and the development of NSCLC are warranted. 36498063 13 39 theme ansamycin 1882:1890 arg1 biosynthesis 1866:1877 decreased biosynthesis 1856:1877 decreased biosynthesis of ansamycin 1856:1890 was positively associated with decreased biosynthesis of ansamycin only (p = 0.001). 36498063 11 40 theme p 1732:1732 arg1 apoptosis 1721:1729 apoptosis 1721:1729 apoptosis (p < 0.001) 1721:1741 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 40 theme p 1732:1732 arg1 < 1734:1734 p < 0.001 1732:1740 p < 0.001 1732:1740 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 7 41 with microbes 1084:1091 arg1 differences 1110:1120 significant differences 1098:1120 significant differences between the patients and controls 1098:1154 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 4 42 theme rRNA 544:547 arg1 amplicons 527:535 Hypervariable V3−V4 amplicons 507:535 Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples 507:582 Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples were sequenced. 36498063 11 43 theme lipoic 1657:1662 arg1 0.039 1685:1689 p = 0.039 1681:1689 p = 0.039 1681:1689 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 43 theme lipoic 1657:1662 arg1 metabolism 1669:1678 lipoic acid metabolism 1657:1678 lipoic acid metabolism (p = 0.039) 1657:1690 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 44 theme N-glycan 1579:1586 arg1 p 1602:1602 p = 0.023 1602:1610 p = 0.023 1602:1610 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 44 theme N-glycan 1579:1586 arg1 biosynthesis 1588:1599 N-glycan biosynthesis 1579:1599 N-glycan biosynthesis (p = 0.023) 1579:1611 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 2 45 theme gut-microbe-related 360:378 arg1 pathways 380:387 possible gut-microbe-related pathways 351:387 possible gut-microbe-related pathways involved in the development of NSCLC 351:424 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 6 46 theme p 940:940 arg1 < 942:942 p < 0.001 940:948 p < 0.001 940:948 Results: Microbial alpha diversity was decreased in the patients with NSCLC, and beta diversity was significantly different between the patients and controls (p < 0.001). 36498063 6 46 theme p 940:940 arg1 patients 917:924 patients 917:924 patients 917:924 Results: Microbial alpha diversity was decreased in the patients with NSCLC, and beta diversity was significantly different between the patients and controls (p < 0.001). 36498063 11 47 theme = 1604:1604 arg1 p 1602:1602 p = 0.023 1602:1610 p = 0.023 1602:1610 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 47 theme = 1604:1604 arg1 biosynthesis 1588:1599 N-glycan biosynthesis 1579:1599 N-glycan biosynthesis (p = 0.023) 1579:1611 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 4 48 from amplicons 527:535 arg1 samples 576:582 freshly collected fecal samples 552:582 freshly collected fecal samples 552:582 Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples were sequenced. 36498063 17 49 theme Further 2224:2230 arg1 investigations 2232:2245 Further investigations 2224:2245 Further investigations on the mechanism underlying the potential association between gut dysbiosis 2224:2321 Further investigations on the mechanism underlying the potential association between gut dysbiosis and the development of NSCLC are warranted. 36498063 16 50 theme Bacteroides 2071:2081 arg1 caccae 2083:2088 Bacteroides caccae 2071:2088 Bacteroides caccae 2071:2088 and Bacteroides caccae were abundant and may be associated with the risk of NSCLC regardless of sex, smoking history, and gut-microbe-related comorbidities. 36498063 2 51 theme lung 283:286 arg1 NSCLC 296:300 NSCLC 296:300 NSCLC 296:300 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 2 51 theme lung 283:286 arg1 cancer 288:293 treatment-naïve non-small-cell lung cancer 252:293 age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients 240:310 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 11 52 theme glycosaminoglycan 1614:1630 arg1 degradation 1632:1642 glycosaminoglycan degradation 1614:1642 glycosaminoglycan degradation (p < 0.001) 1614:1654 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 52 theme glycosaminoglycan 1614:1630 arg1 < 1647:1647 p < 0.001 1645:1653 p < 0.001 1645:1653 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 5 53 theme functional 634:643 arg1 pathways 645:652 functional pathways 634:652 functional pathways 634:652 Diversity, microbial composition, functional pathways, smoking history, and gut-microbe-related comorbidities were analyzed to assess the factors associated with the risk of NSCLC. 36498063 11 54 theme caccae 1499:1504 arg1 abundance 1474:1482 the abundance 1470:1482 the abundance of Bacteroides caccae 1470:1504 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 2 55 theme treatment-naïve 252:266 arg1 NSCLC 296:300 NSCLC 296:300 NSCLC 296:300 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 2 55 theme treatment-naïve 252:266 arg1 cancer 288:293 treatment-naïve non-small-cell lung cancer 252:293 age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients 240:310 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 8 56 theme increased 1240:1248 arg1 risk 1250:1253 an increased risk 1237:1253 an increased risk of NSCLC 1237:1262 and Bacteroides caccae was associated with an increased risk of NSCLC (p = 0.003 and 0.007, respectively). 36498063 7 57 theme abundant 1075:1082 arg1 microbes 1084:1091 11 abundant microbes 1072:1091 11 abundant microbes with significant differences between the patients and controls 1072:1154 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 11 58 theme hormone 1545:1551 arg1 biosynthesis 1553:1564 steroid hormone biosynthesis 1537:1564 steroid hormone biosynthesis (p < 0.001) 1537:1576 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 58 theme hormone 1545:1551 arg1 < 1569:1569 p < 0.001 1567:1575 p < 0.001 1567:1575 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 1 59 theme malignant 150:158 arg1 diseases 160:167 various malignant diseases 142:167 various malignant diseases 142:167 Background: The imbalance of gut microbiota, dysbiosis, is associated with various malignant diseases. 36498063 6 60 with patients 837:844 arg1 NSCLC 851:855 NSCLC 851:855 NSCLC 851:855 Results: Microbial alpha diversity was decreased in the patients with NSCLC, and beta diversity was significantly different between the patients and controls (p < 0.001). 36498063 6 61 theme Microbial 790:798 arg1 diversity 806:814 Microbial alpha diversity 790:814 Microbial alpha diversity 790:814 Results: Microbial alpha diversity was decreased in the patients with NSCLC, and beta diversity was significantly different between the patients and controls (p < 0.001). 36498063 8 62 theme Bacteroides 1198:1208 arg1 caccae 1210:1215 Bacteroides caccae 1198:1215 Bacteroides caccae 1198:1215 and Bacteroides caccae was associated with an increased risk of NSCLC (p = 0.003 and 0.007, respectively). 36498063 17 63 theme gut 2309:2311 arg1 dysbiosis 2313:2321 gut dysbiosis 2309:2321 gut dysbiosis 2309:2321 Further investigations on the mechanism underlying the potential association between gut dysbiosis and the development of NSCLC are warranted. 36498063 7 64 theme obstructive 1037:1047 arg1 disease 1059:1065 chronic obstructive pulmonary disease 1029:1065 chronic obstructive pulmonary disease 1029:1065 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 4 65 theme V3−V4 521:525 arg1 amplicons 527:535 Hypervariable V3−V4 amplicons 507:535 Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples 507:582 Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples were sequenced. 36498063 16 66 theme NSCLC 2143:2147 arg1 risk 2135:2138 the risk 2131:2138 the risk of NSCLC 2131:2147 and Bacteroides caccae were abundant and may be associated with the risk of NSCLC regardless of sex, smoking history, and gut-microbe-related comorbidities. 36498063 1 67 theme microbiota 100:109 arg1 imbalance 83:91 The imbalance 79:91 The imbalance of gut microbiota, dysbiosis, 79:121 Background: The imbalance of gut microbiota, dysbiosis, is associated with various malignant diseases. 36498063 17 68 from development 2331:2341 arg1 mechanism 2254:2262 the mechanism 2250:2262 the mechanism underlying the potential association between gut dysbiosis 2250:2321 Further investigations on the mechanism underlying the potential association between gut dysbiosis and the development of NSCLC are warranted. 36498063 11 69 theme p 1681:1681 arg1 0.039 1685:1689 p = 0.039 1681:1689 p = 0.039 1681:1689 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 69 theme p 1681:1681 arg1 metabolism 1669:1678 lipoic acid metabolism 1657:1678 lipoic acid metabolism (p = 0.039) 1657:1690 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 5 70 theme NSCLC 774:778 arg1 risk 766:769 the risk 762:769 the risk of NSCLC 762:778 Diversity, microbial composition, functional pathways, smoking history, and gut-microbe-related comorbidities were analyzed to assess the factors associated with the risk of NSCLC. 36498063 2 71 theme gut 222:224 arg1 microbiota 226:235 gut microbiota 222:235 gut microbiota 222:235 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 7 72 with history 987:993 arg1 differences 1110:1120 significant differences 1098:1120 significant differences between the patients and controls 1098:1154 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 4 73 theme Hypervariable 507:519 arg1 amplicons 527:535 Hypervariable V3−V4 amplicons 507:535 Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples 507:582 Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples were sequenced. 36498063 7 74 theme smoking 979:985 arg1 history 987:993 smoking history 979:993 smoking history 979:993 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 15 75 theme fecal 2042:2046 arg1 Anaerotruncus 2048:2060 fecal Anaerotruncus 2042:2060 fecal Anaerotruncus 2042:2060 Conclusions: Our results revealed that fecal Anaerotruncus spp. 36498063 7 76 with hypertension 996:1007 arg1 differences 1110:1120 significant differences 1098:1120 significant differences between the patients and controls 1098:1154 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 14 77 theme Bacteroides 1962:1972 arg1 caccae 1974:1979 Bacteroides caccae or Anaerotruncus spp 1962:2000 caccae 1974:1979 No overlapping signaling pathways were modulated by Bacteroides caccae or Anaerotruncus spp. 36498063 5 78 theme microbial 611:619 arg1 composition 621:631 microbial composition 611:631 microbial composition 611:631 Diversity, microbial composition, functional pathways, smoking history, and gut-microbe-related comorbidities were analyzed to assess the factors associated with the risk of NSCLC. 36498063 10 79 theme Bacteroides 1406:1416 arg1 caccae 1418:1423 Bacteroides caccae 1406:1423 Bacteroides caccae 1406:1423 and Bacteroides caccae, respectively (both p < 0.001). 36498063 13 80 theme = 1900:1900 arg1 p 1898:1898 p = 0.001 1898:1906 p = 0.001 1898:1906 was positively associated with decreased biosynthesis of ansamycin only (p = 0.001). 36498063 3 81 theme healthy 486:492 arg1 individuals 494:504 268 healthy individuals 482:504 268 healthy individuals 482:504 Methods: We enrolled 34 age-matched NSCLC patients and 268 healthy individuals. 36498063 11 82 theme glycerolipid 1769:1780 arg1 metabolism 1782:1791 glycerolipid metabolism 1769:1791 glycerolipid metabolism (p < 0.001) 1769:1803 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 82 theme glycerolipid 1769:1780 arg1 < 1796:1796 p < 0.001 1794:1802 p < 0.001 1794:1802 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 7 83 theme Anaerotruncus 1175:1187 arg1 enrichment 1161:1170 the enrichment 1157:1170 the enrichment of Anaerotruncus 1157:1187 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 4 84 theme collected 560:568 arg1 samples 576:582 freshly collected fecal samples 552:582 freshly collected fecal samples 552:582 Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples were sequenced. 36498063 0 85 theme Dysbiosis 14:22 arg1 Impact 0:5 Impact 0:5 Impact of Gut Dysbiosis on the Risk of Non-Small-Cell Lung Cancer 0:64 Impact of Gut Dysbiosis on the Risk of Non-Small-Cell Lung Cancer. 36498063 7 86 with disease 1059:1065 arg1 differences 1110:1120 significant differences 1098:1120 significant differences between the patients and controls 1098:1154 After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. 36498063 14 87 theme overlapping 1913:1923 arg1 pathways 1935:1942 No overlapping signaling pathways 1910:1942 No overlapping signaling pathways 1910:1942 No overlapping signaling pathways were modulated by Bacteroides caccae or Anaerotruncus spp. 36498063 11 88 theme p 1645:1645 arg1 degradation 1632:1642 glycosaminoglycan degradation 1614:1642 glycosaminoglycan degradation (p < 0.001) 1614:1654 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 88 theme p 1645:1645 arg1 < 1647:1647 p < 0.001 1645:1653 p < 0.001 1645:1653 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 2 89 theme NSCLC 420:424 arg1 development 405:415 the development 401:415 the development of NSCLC 401:424 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 9 90 theme characteristic 1336:1349 arg1 curves 1351:1356 characteristic curves 1336:1356 characteristic curves 1336:1356 The areas under receiver operating characteristic curves were 71.4% and 66.9% for Anaerotruncus spp. 36498063 4 91 theme 16S 540:542 arg1 rRNA 544:547 16S rRNA 540:547 16S rRNA 540:547 Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples were sequenced. 36498063 11 92 theme p 1567:1567 arg1 biosynthesis 1553:1564 steroid hormone biosynthesis 1537:1564 steroid hormone biosynthesis (p < 0.001) 1537:1576 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 11 92 theme p 1567:1567 arg1 < 1569:1569 p < 0.001 1567:1575 p < 0.001 1567:1575 Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). 36498063 3 93 theme age-matched 451:461 arg1 patients 469:476 34 age-matched NSCLC patients 448:476 34 age-matched NSCLC patients 448:476 Methods: We enrolled 34 age-matched NSCLC patients and 268 healthy individuals. 36498063 10 94 dep respectively 1426:1437 arg1 p 1445:1445 both p < 0.001 1440:1453 both p < 0.001 1440:1453 and Bacteroides caccae, respectively (both p < 0.001). 36498063 6 95 theme beta 862:865 arg1 diversity 867:875 beta diversity 862:875 beta diversity 862:875 Results: Microbial alpha diversity was decreased in the patients with NSCLC, and beta diversity was significantly different between the patients and controls (p < 0.001). 36498063 2 96 theme healthy 316:322 arg1 individuals 324:334 healthy individuals 316:334 healthy individuals 316:334 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36498063 6 97 dep patients 917:924 arg1 the 913:915 the 913:915 the 913:915 Results: Microbial alpha diversity was decreased in the patients with NSCLC, and beta diversity was significantly different between the patients and controls (p < 0.001). 36498063 13 98 theme decreased 1856:1864 arg1 biosynthesis 1866:1877 decreased biosynthesis 1856:1877 decreased biosynthesis of ansamycin 1856:1890 was positively associated with decreased biosynthesis of ansamycin only (p = 0.001). 36498063 2 99 theme possible 351:358 arg1 pathways 380:387 possible gut-microbe-related pathways 351:387 possible gut-microbe-related pathways involved in the development of NSCLC 351:424 This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. 36904440 12 0 theme application 1898:1908 arg1 potential 1881:1889 the potential 1877:1889 the potential of the application of LPVI to decipher vegetation change 1877:1946 This confirms the potential of the application of LPVI to decipher vegetation change, even in a dynamic system as the peatland. 36904440 4 1 theme lignin 551:556 arg1 concentrations 533:546 greater concentrations 525:546 greater concentrations of lignin 525:556 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 1 2 theme dioxide 254:260 arg1 matter 207:212 organic matter 199:212 organic matter (OM) 199:217 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 1 2 theme dioxide 254:260 arg1 source 237:242 a significant source 223:242 a significant source of carbon dioxide (CO2) and methane (CH4) 223:284 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 1 2 theme dioxide 254:260 arg1 OM 215:216 OM 215:216 OM 215:216 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 7 3 theme CuO-NaOH 1365:1372 arg1 oxidation 1374:1382 CuO-NaOH oxidation 1365:1382 CuO-NaOH oxidation 1365:1382 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 7 4 theme lignin 1313:1318 arg1 phenols 1320:1326 lignin phenols 1313:1326 lignin phenols 1313:1326 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 6 5 theme investigated 1144:1155 arg1 column 1162:1167 the investigated peat column 1140:1167 the investigated peat column called "Sagnes" 1140:1183 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 13 6 theme peat 2031:2034 arg1 samples 2036:2042 the depth peat samples 2021:2042 the depth peat samples 2021:2042 The population is composed of the depth peat samples, and the variables are the proxies and relative contributions of the 11 yielded phenolic sub-units. 36904440 1 7 theme Tropical 169:176 arg1 Peatlands 178:186 Tropical Peatlands 169:186 Tropical Peatlands 169:186 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 7 8 theme distribution 1297:1308 arg1 basis 1275:1279 the basis 1271:1279 the basis of the relative distribution of lignin phenols 1271:1326 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 4 9 theme CH4 611:613 arg1 concentrations 615:628 the high CO2 and CH4 concentrations 594:628 concentrations 615:628 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 4 10 from related 583:589 arg1 peat 669:672 the surface peat 657:672 the surface peat 657:672 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 0 11 theme Moieties 120:127 arg1 Case 105:108 Peatlands: Case 94:108 Peatlands: Case of Lignin Moieties 94:127 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 6 12 theme lignin 1113:1118 arg1 sample 1120:1125 the lignin sample 1109:1125 the lignin sample presented in the investigated peat column called "Sagnes" 1109:1183 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 11 13 theme higher 1818:1823 arg1 correlation 1825:1835 a higher correlation 1816:1835 a higher correlation with PC1 rather than PC2 1816:1860 LPVI showed a higher correlation with PC1 rather than PC2. 36904440 3 14 located present 452:458 arg1 ecosystems 472:481 peatland ecosystems 463:481 peatland ecosystems 463:481 The composition of organic macromolecules that are present in peatland ecosystems are mainly lignin and polysaccharides. 36904440 3 14 located present 452:458 arg2 macromolecules 428:441 organic macromolecules 420:441 organic macromolecules that are present in peatland ecosystems 420:481 The composition of organic macromolecules that are present in peatland ecosystems are mainly lignin and polysaccharides. 36904440 5 15 theme " 823:823 arg1 preferable 846:855 preferable 846:855 preferable 846:855 In this study, we found that the "Wet Chemical Degradation" approach is the most preferable and qualified to evaluate the lignin degradation in soils accurately. 36904440 5 15 theme " 823:823 arg1 approach 825:832 the "Wet Chemical Degradation" approach 794:832 the "Wet Chemical Degradation" approach 794:832 In this study, we found that the "Wet Chemical Degradation" approach is the most preferable and qualified to evaluate the lignin degradation in soils accurately. 36904440 7 16 theme degradation 1250:1260 arg1 state 1262:1266 lignin degradation state 1243:1266 lignin degradation state on the basis of the relative distribution of lignin phenols 1243:1326 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 0 17 theme Oxidative 149:157 arg1 Cleavage 159:166 Alkaline Oxidative Cleavage 140:166 Alkaline Oxidative Cleavage 140:166 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 13 18 theme phenolic 2124:2131 arg1 sub-units 2133:2141 the 11 yielded phenolic sub-units 2109:2141 the 11 yielded phenolic sub-units 2109:2141 The population is composed of the depth peat samples, and the variables are the proxies and relative contributions of the 11 yielded phenolic sub-units. 36904440 6 19 theme alkaline 1086:1093 arg1 hydrolysis 1095:1104 alkaline hydrolysis 1086:1104 alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes" 1086:1183 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 12 20 theme LPVI 1913:1916 arg1 application 1898:1908 the application 1894:1908 the application of LPVI 1894:1916 This confirms the potential of the application of LPVI to decipher vegetation change, even in a dynamic system as the peatland. 36904440 10 21 used used 1783:1786 arg2 LPVI 1774:1777 LPVI 1774:1777 LPVI 1774:1777 Lignin phenol vegetation index (LPVI) is used for comparison. 36904440 10 21 used used 1783:1786 arg2 index 1767:1771 Lignin phenol vegetation index 1742:1771 Lignin phenol vegetation index (LPVI) 1742:1778 Lignin phenol vegetation index (LPVI) is used for comparison. 36904440 13 22 theme relative 2083:2090 arg1 contributions 2092:2104 relative contributions 2083:2104 relative contributions 2083:2104 The population is composed of the depth peat samples, and the variables are the proxies and relative contributions of the 11 yielded phenolic sub-units. 36904440 8 23 theme phenolic 1527:1534 arg1 sub-units 1536:1544 the phenolic sub-units 1523:1544 the phenolic sub-units 1523:1544 In order to achieve this aim, the so-called Principal Component Analysis (PCA) has been applied for the molecular fingerprint composed of the phenolic sub-units, yielded by CuO-NaOH oxidation. 36904440 9 24 theme proxies 1645:1651 arg1 efficiency 1609:1618 the efficiency 1605:1618 the efficiency of the already available proxies 1605:1651 This approach aims to seek the efficiency of the already available proxies and potentially create new ones for the investigation of lignin burial along a peatland. 36904440 13 25 dep proxies 2071:2077 arg1 the 2067:2069 the 2067:2069 the 2067:2069 The population is composed of the depth peat samples, and the variables are the proxies and relative contributions of the 11 yielded phenolic sub-units. 36904440 5 26 theme Chemical 803:810 arg1 preferable 846:855 preferable 846:855 preferable 846:855 In this study, we found that the "Wet Chemical Degradation" approach is the most preferable and qualified to evaluate the lignin degradation in soils accurately. 36904440 5 26 theme Chemical 803:810 arg1 approach 825:832 the "Wet Chemical Degradation" approach 794:832 the "Wet Chemical Degradation" approach 794:832 In this study, we found that the "Wet Chemical Degradation" approach is the most preferable and qualified to evaluate the lignin degradation in soils accurately. 36904440 4 27 theme surface 661:667 arg1 peat 669:672 the surface peat 657:672 the surface peat 657:672 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 9 28 theme new 1676:1678 arg1 ones 1680:1683 new ones 1676:1683 new ones for the investigation of lignin burial along a peatland 1676:1739 This approach aims to seek the efficiency of the already available proxies and potentially create new ones for the investigation of lignin burial along a peatland. 36904440 7 29 theme indicators 1228:1237 arg1 development 1190:1200 The development 1186:1200 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols 1186:1326 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 8 30 theme so-called 1419:1427 arg1 PCA 1459:1461 PCA 1459:1461 PCA 1459:1461 In order to achieve this aim, the so-called Principal Component Analysis (PCA) has been applied for the molecular fingerprint composed of the phenolic sub-units, yielded by CuO-NaOH oxidation. 36904440 8 30 theme so-called 1419:1427 arg1 Analysis 1449:1456 the so-called Principal Component Analysis 1415:1456 the so-called Principal Component Analysis (PCA) 1415:1462 In order to achieve this aim, the so-called Principal Component Analysis (PCA) has been applied for the molecular fingerprint composed of the phenolic sub-units, yielded by CuO-NaOH oxidation. 36904440 7 31 theme various 1205:1211 arg1 indicators 1228:1237 various characteristic indicators 1205:1237 various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols 1205:1326 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 8 32 theme Component 1439:1447 arg1 PCA 1459:1461 PCA 1459:1461 PCA 1459:1461 In order to achieve this aim, the so-called Principal Component Analysis (PCA) has been applied for the molecular fingerprint composed of the phenolic sub-units, yielded by CuO-NaOH oxidation. 36904440 8 32 theme Component 1439:1447 arg1 Analysis 1449:1456 the so-called Principal Component Analysis 1415:1456 the so-called Principal Component Analysis (PCA) 1415:1462 In order to achieve this aim, the so-called Principal Component Analysis (PCA) has been applied for the molecular fingerprint composed of the phenolic sub-units, yielded by CuO-NaOH oxidation. 36904440 0 33 theme Unsupervised 15:26 arg1 Learning 28:35 Unsupervised Learning 15:35 Unsupervised Learning 15:35 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 9 34 theme lignin 1710:1715 arg1 burial 1717:1722 lignin burial 1710:1722 lignin burial 1710:1722 This approach aims to seek the efficiency of the already available proxies and potentially create new ones for the investigation of lignin burial along a peatland. 36904440 10 35 theme Lignin 1742:1747 arg1 index 1767:1771 Lignin phenol vegetation index 1742:1771 Lignin phenol vegetation index (LPVI) 1742:1778 Lignin phenol vegetation index (LPVI) is used for comparison. 36904440 10 35 theme Lignin 1742:1747 arg1 LPVI 1774:1777 LPVI 1774:1777 LPVI 1774:1777 Lignin phenol vegetation index (LPVI) is used for comparison. 36904440 2 36 theme peat 355:358 arg1 profile 360:366 the peat profile 351:366 the peat profile 351:366 However, it is still ambiguous where in the peat profile these OM and gases are produced. 36904440 1 37 theme methane 272:278 arg1 matter 207:212 organic matter 199:212 organic matter (OM) 199:217 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 1 37 theme methane 272:278 arg1 source 237:242 a significant source 223:242 a significant source of carbon dioxide (CO2) and methane (CH4) 223:284 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 1 37 theme methane 272:278 arg1 OM 215:216 OM 215:216 OM 215:216 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 0 38 theme Burial 59:64 arg1 Behavior 66:73 Burial Behavior 59:73 Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties 59:127 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 3 39 theme macromolecules 428:441 arg1 lignin 494:499 lignin 494:499 lignin 494:499 The composition of organic macromolecules that are present in peatland ecosystems are mainly lignin and polysaccharides. 36904440 3 39 theme macromolecules 428:441 arg1 composition 405:415 The composition 401:415 The composition of organic macromolecules that are present in peatland ecosystems 401:481 The composition of organic macromolecules that are present in peatland ecosystems are mainly lignin and polysaccharides. 36904440 3 40 attach present 452:458 arg1 ecosystems 472:481 peatland ecosystems 463:481 peatland ecosystems 463:481 The composition of organic macromolecules that are present in peatland ecosystems are mainly lignin and polysaccharides. 36904440 3 40 attach present 452:458 arg2 macromolecules 428:441 organic macromolecules 420:441 organic macromolecules that are present in peatland ecosystems 420:481 The composition of organic macromolecules that are present in peatland ecosystems are mainly lignin and polysaccharides. 36904440 10 41 theme vegetation 1756:1765 arg1 index 1767:1771 Lignin phenol vegetation index 1742:1771 Lignin phenol vegetation index (LPVI) 1742:1778 Lignin phenol vegetation index (LPVI) is used for comparison. 36904440 10 41 theme vegetation 1756:1765 arg1 LPVI 1774:1777 LPVI 1774:1777 LPVI 1774:1777 Lignin phenol vegetation index (LPVI) is used for comparison. 36904440 13 42 theme depth 2025:2029 arg1 samples 2036:2042 the depth peat samples 2021:2042 the depth peat samples 2021:2042 The population is composed of the depth peat samples, and the variables are the proxies and relative contributions of the 11 yielded phenolic sub-units. 36904440 6 43 theme major 995:999 arg1 sub-units 1010:1018 11 major phenolic sub-units 992:1018 11 major phenolic sub-units produced by alkaline oxidation 992:1049 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 8 44 theme molecular 1489:1497 arg1 fingerprint 1499:1509 the molecular fingerprint 1485:1509 the molecular fingerprint composed of the phenolic sub-units, yielded by CuO-NaOH oxidation 1485:1575 In order to achieve this aim, the so-called Principal Component Analysis (PCA) has been applied for the molecular fingerprint composed of the phenolic sub-units, yielded by CuO-NaOH oxidation. 36904440 6 45 theme Sagnes 1177:1182 arg1 " 1183:1183 Sagnes" 1177:1183 Sagnes" 1177:1183 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 8 46 theme CuO-NaOH 1558:1565 arg1 oxidation 1567:1575 CuO-NaOH oxidation 1558:1575 CuO-NaOH oxidation 1558:1575 In order to achieve this aim, the so-called Principal Component Analysis (PCA) has been applied for the molecular fingerprint composed of the phenolic sub-units, yielded by CuO-NaOH oxidation. 36904440 4 47 theme greater 525:531 arg1 concentrations 533:546 greater concentrations 525:546 greater concentrations of lignin 525:556 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 3 48 from present 452:458 arg1 ecosystems 472:481 peatland ecosystems 463:481 peatland ecosystems 463:481 The composition of organic macromolecules that are present in peatland ecosystems are mainly lignin and polysaccharides. 36904440 1 49 theme carbon 247:252 arg1 CO2 263:265 CO2 263:265 CO2 263:265 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 1 49 theme carbon 247:252 arg1 dioxide 254:260 carbon dioxide 247:260 carbon dioxide (CO2) 247:266 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 6 50 theme peat 1157:1160 arg1 column 1162:1167 the investigated peat column 1140:1167 the investigated peat column called "Sagnes" 1140:1183 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 7 51 theme phenols 1320:1326 arg1 distribution 1297:1308 the relative distribution 1284:1308 the relative distribution of lignin phenols 1284:1326 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 4 52 theme high 598:601 arg1 CO2 603:605 the high CO2 and CH4 concentrations 594:628 CO2 603:605 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 5 53 from degradation 894:904 arg1 soils 909:913 soils 909:913 soils 909:913 In this study, we found that the "Wet Chemical Degradation" approach is the most preferable and qualified to evaluate the lignin degradation in soils accurately. 36904440 6 54 theme cupric 1057:1062 arg1 oxide 1064:1068 cupric oxide 1057:1068 cupric oxide 1057:1068 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 0 55 theme Lignin 113:118 arg1 Moieties 120:127 Lignin Moieties 113:127 Lignin Moieties 113:127 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 1 56 theme organic 199:205 arg1 matter 207:212 organic matter 199:212 organic matter (OM) 199:217 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 1 56 theme organic 199:205 arg1 OM 215:216 OM 215:216 OM 215:216 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 0 57 from Geomaterials 78:89 arg1 Case 105:108 Peatlands: Case 94:108 Peatlands: Case of Lignin Moieties 94:127 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 7 58 theme relative 1288:1295 arg1 distribution 1297:1308 the relative distribution 1284:1308 the relative distribution of lignin phenols 1284:1326 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 0 59 from Behavior 66:73 arg1 Case 105:108 Peatlands: Case 94:108 Peatlands: Case of Lignin Moieties 94:127 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 6 60 theme sample 1120:1125 arg1 hydrolysis 1095:1104 alkaline hydrolysis 1086:1104 alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes" 1086:1183 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 12 61 theme dynamic 1959:1965 arg1 system 1967:1972 a dynamic system 1957:1972 a dynamic system as the peatland 1957:1988 This confirms the potential of the application of LPVI to decipher vegetation change, even in a dynamic system as the peatland. 36904440 0 62 theme Alkaline 140:147 arg1 Cleavage 159:166 Alkaline Oxidative Cleavage 140:166 Alkaline Oxidative Cleavage 140:166 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 5 63 theme Degradation 812:822 arg1 preferable 846:855 preferable 846:855 preferable 846:855 In this study, we found that the "Wet Chemical Degradation" approach is the most preferable and qualified to evaluate the lignin degradation in soils accurately. 36904440 5 63 theme Degradation 812:822 arg1 approach 825:832 the "Wet Chemical Degradation" approach 794:832 the "Wet Chemical Degradation" approach 794:832 In this study, we found that the "Wet Chemical Degradation" approach is the most preferable and qualified to evaluate the lignin degradation in soils accurately. 36904440 0 64 from Case 105:108 arg1 Behavior 66:73 Burial Behavior 59:73 Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties 59:127 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 12 65 theme vegetation 1930:1939 arg1 change 1941:1946 vegetation change 1930:1946 vegetation change 1930:1946 This confirms the potential of the application of LPVI to decipher vegetation change, even in a dynamic system as the peatland. 36904440 13 66 theme yielded 2116:2122 arg1 sub-units 2133:2141 the 11 yielded phenolic sub-units 2109:2141 the 11 yielded phenolic sub-units 2109:2141 The population is composed of the depth peat samples, and the variables are the proxies and relative contributions of the 11 yielded phenolic sub-units. 36904440 6 67 dep hydrolysis 1095:1104 arg1 II 1071:1072 II 1071:1072 II 1071:1072 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 0 68 theme Behavior 66:73 arg1 Evaluation 45:54 the Evaluation 41:54 the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties 41:127 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 13 69 theme sub-units 2133:2141 arg1 contributions 2092:2104 relative contributions 2083:2104 relative contributions 2083:2104 The population is composed of the depth peat samples, and the variables are the proxies and relative contributions of the 11 yielded phenolic sub-units. 36904440 13 69 theme sub-units 2133:2141 arg1 variables 2053:2061 the variables 2049:2061 the variables 2049:2061 The population is composed of the depth peat samples, and the variables are the proxies and relative contributions of the 11 yielded phenolic sub-units. 36904440 13 69 theme sub-units 2133:2141 arg1 proxies 2071:2077 proxies 2071:2077 proxies 2071:2077 The population is composed of the depth peat samples, and the variables are the proxies and relative contributions of the 11 yielded phenolic sub-units. 36904440 9 70 theme available 1635:1643 arg1 proxies 1645:1651 the already available proxies 1623:1651 the already available proxies 1623:1651 This approach aims to seek the efficiency of the already available proxies and potentially create new ones for the investigation of lignin burial along a peatland. 36904440 7 71 theme lignin 1243:1248 arg1 state 1262:1266 lignin degradation state 1243:1266 lignin degradation state on the basis of the relative distribution of lignin phenols 1243:1326 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 3 72 from ecosystems 472:481 arg1 present 452:458 present 452:458 present 452:458 The composition of organic macromolecules that are present in peatland ecosystems are mainly lignin and polysaccharides. 36904440 0 73 theme Geomaterials 78:89 arg1 Behavior 66:73 Burial Behavior 59:73 Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties 59:127 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 1 74 theme anoxic 292:297 arg1 conditions 299:308 anoxic conditions 292:308 anoxic conditions 292:308 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 36904440 5 75 theme Wet 799:801 arg1 preferable 846:855 preferable 846:855 preferable 846:855 In this study, we found that the "Wet Chemical Degradation" approach is the most preferable and qualified to evaluate the lignin degradation in soils accurately. 36904440 5 75 theme Wet 799:801 arg1 approach 825:832 the "Wet Chemical Degradation" approach 794:832 the "Wet Chemical Degradation" approach 794:832 In this study, we found that the "Wet Chemical Degradation" approach is the most preferable and qualified to evaluate the lignin degradation in soils accurately. 36904440 4 76 theme anoxic 636:641 arg1 conditions 643:652 anoxic conditions 636:652 anoxic conditions 636:652 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 0 77 theme Peatlands 94:102 arg1 Case 105:108 Peatlands: Case 94:108 Peatlands: Case of Lignin Moieties 94:127 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 11 78 with correlation 1825:1835 arg1 PC1 1842:1844 PC1 1842:1844 PC1 rather than PC2 1842:1860 LPVI showed a higher correlation with PC1 rather than PC2. 36904440 11 78 with correlation 1825:1835 arg1 PC2 1858:1860 PC2 1858:1860 PC1 rather than PC2 1842:1860 LPVI showed a higher correlation with PC1 rather than PC2. 36904440 7 79 theme characteristic 1213:1226 arg1 indicators 1228:1237 various characteristic indicators 1205:1237 various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols 1205:1326 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 8 80 theme Principal 1429:1437 arg1 PCA 1459:1461 PCA 1459:1461 PCA 1459:1461 In order to achieve this aim, the so-called Principal Component Analysis (PCA) has been applied for the molecular fingerprint composed of the phenolic sub-units, yielded by CuO-NaOH oxidation. 36904440 8 80 theme Principal 1429:1437 arg1 Analysis 1449:1456 the so-called Principal Component Analysis 1415:1456 the so-called Principal Component Analysis (PCA) 1415:1462 In order to achieve this aim, the so-called Principal Component Analysis (PCA) has been applied for the molecular fingerprint composed of the phenolic sub-units, yielded by CuO-NaOH oxidation. 36904440 7 81 from state 1262:1266 arg1 basis 1275:1279 the basis 1271:1279 the basis of the relative distribution of lignin phenols 1271:1326 The development of various characteristic indicators for lignin degradation state on the basis of the relative distribution of lignin phenols was measured by chromatography after CuO-NaOH oxidation. 36904440 6 82 theme molecular 956:964 arg1 fingerprint 966:976 the molecular fingerprint 952:976 the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation 952:1049 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 0 83 theme Learning 28:35 arg1 Application 0:10 Application 0:10 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties 0:127 Application of Unsupervised Learning for the Evaluation of Burial Behavior of Geomaterials in Peatlands: Case of Lignin Moieties Yielded by Alkaline Oxidative Cleavage. 36904440 10 84 theme phenol 1749:1754 arg1 index 1767:1771 Lignin phenol vegetation index 1742:1771 Lignin phenol vegetation index (LPVI) 1742:1778 Lignin phenol vegetation index (LPVI) is used for comparison. 36904440 10 84 theme phenol 1749:1754 arg1 LPVI 1774:1777 LPVI 1774:1777 LPVI 1774:1777 Lignin phenol vegetation index (LPVI) is used for comparison. 36904440 9 85 theme burial 1717:1722 arg1 investigation 1693:1705 the investigation 1689:1705 the investigation of lignin burial along a peatland 1689:1739 This approach aims to seek the efficiency of the already available proxies and potentially create new ones for the investigation of lignin burial along a peatland. 36904440 4 86 theme oxic 736:739 arg1 conditions 741:750 anoxic and oxic conditions 725:750 conditions 741:750 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 6 87 theme alkaline 1032:1039 arg1 oxidation 1041:1049 alkaline oxidation 1032:1049 alkaline oxidation 1032:1049 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 4 88 from peat 669:672 arg1 related 583:589 related 583:589 related 583:589 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 5 89 theme lignin 887:892 arg1 degradation 894:904 the lignin degradation 883:904 the lignin degradation in soils 883:913 In this study, we found that the "Wet Chemical Degradation" approach is the most preferable and qualified to evaluate the lignin degradation in soils accurately. 36904440 4 90 theme lignin 712:717 arg1 degradation 697:707 the degradation 693:707 the degradation of lignin 693:717 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 3 91 theme organic 420:426 arg1 macromolecules 428:441 organic macromolecules 420:441 organic macromolecules that are present in peatland ecosystems 420:481 The composition of organic macromolecules that are present in peatland ecosystems are mainly lignin and polysaccharides. 36904440 6 92 theme phenolic 1001:1008 arg1 sub-units 1010:1018 11 major phenolic sub-units 992:1018 11 major phenolic sub-units produced by alkaline oxidation 992:1049 Then, we applied PCA for the molecular fingerprint consisting of 11 major phenolic sub-units produced by alkaline oxidation using cupric oxide (II) along with alkaline hydrolysis of the lignin sample presented in the investigated peat column called "Sagnes". 36904440 4 93 theme anoxic 725:730 arg1 conditions 741:750 anoxic and oxic conditions 725:750 conditions 741:750 As greater concentrations of lignin are found to be strongly related to the high CO2 and CH4 concentrations under anoxic conditions in the surface peat, the need to study the degradation of lignin under anoxic and oxic conditions has emerged. 36904440 3 94 theme peatland 463:470 arg1 ecosystems 472:481 peatland ecosystems 463:481 peatland ecosystems 463:481 The composition of organic macromolecules that are present in peatland ecosystems are mainly lignin and polysaccharides. 36904440 1 95 theme significant 225:235 arg1 source 237:242 a significant source 223:242 a significant source of carbon dioxide (CO2) and methane (CH4) 223:284 Tropical Peatlands accumulate organic matter (OM) and a significant source of carbon dioxide (CO2) and methane (CH4) under anoxic conditions. 35897636 0 0 theme Quorum 94:99 arg1 Sensing 101:107 Quorum Sensing 94:107 Quorum Sensing System Autoinducer-2 Activity 94:137 Boron Derivatives Accelerate Biofilm Formation of Recombinant Escherichia coli via Increasing Quorum Sensing System Autoinducer-2 Activity. 35897636 11 1 theme AI-2 1526:1529 arg1 activity 1531:1538 the QS system AI-2 activity 1512:1538 the QS system AI-2 activity 1512:1538 These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli. 35897636 10 2 theme sensing 1327:1333 arg1 genes 1335:1339 quorum sensing genes 1320:1339 quorum sensing genes 1320:1339 Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. 35897636 3 3 theme intracellular 483:495 arg1 enzymes 497:503 intracellular enzymes 483:503 intracellular enzymes 483:503 However, it is unclear how boron affects biofilm formation in E. coli, particularly recombinant E. coli with intracellular enzymes. 35897636 8 4 with treatment 1047:1055 arg1 H3BO3 1062:1066 H3BO3 1062:1066 H3BO3 (0.6 mM) 1062:1075 Moreover, treatment with H3BO3 (0.6 mM) increased biomass by 88.54%. 35897636 8 4 with treatment 1047:1055 arg1 mM 1073:1074 0.6 mM 1069:1074 0.6 mM 1069:1074 Moreover, treatment with H3BO3 (0.6 mM) increased biomass by 88.54%. 35897636 9 5 contain had 1131:1133 arg1 Meanwhile 1106:1114 Meanwhile 1106:1114 Meanwhile 1106:1114 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 9 5 contain had 1131:1133 arg1 activity 1122:1129 AI-2 activity 1117:1129 AI-2 activity 1117:1129 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 9 5 contain had 1131:1133 arg2 correlation 1144:1154 a linear correlation 1135:1154 a linear correlation with polysaccharides and protein of EPS 1135:1194 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 7 6 theme Na2B4O7 1017:1023 arg1 > 1025:1027 Na2B4O7 > 1017:1027 Na2B4O7 > 1017:1027 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 9 7 theme 0-0.6 1199:1203 arg1 mM 1205:1206 mM 1205:1206 mM 1205:1206 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 10 8 theme quorum 1320:1325 arg1 genes 1335:1339 quorum sensing genes 1320:1339 quorum sensing genes 1320:1339 Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. 35897636 10 9 theme expression 1274:1283 arg1 levels 1285:1290 the expression levels 1270:1290 the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes 1270:1369 Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. 35897636 1 10 theme autoinducer-2 174:186 arg1 synthesis 195:203 autoinducer-2 (AI-2) synthesis 174:203 autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system 174:233 Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. 35897636 7 11 dep increased 906:914 arg1 NaBO3 1030:1034 NaBO3 1030:1034 NaBO3 1030:1034 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 7 11 dep increased 906:914 arg1 > 1012:1014 NaBO2 > 1006:1014 NaBO2 > 1006:1014 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 7 11 dep increased 906:914 arg1 > 1025:1027 Na2B4O7 > 1017:1027 Na2B4O7 > 1017:1027 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 0 12 theme System 109:114 arg1 Activity 130:137 Quorum Sensing System Autoinducer-2 Activity 94:137 Quorum Sensing System Autoinducer-2 Activity 94:137 Boron Derivatives Accelerate Biofilm Formation of Recombinant Escherichia coli via Increasing Quorum Sensing System Autoinducer-2 Activity. 35897636 9 13 theme mM 1205:1206 arg1 H3BO3 1208:1212 0-0.6 mM H3BO3 1199:1212 0-0.6 mM H3BO3 1199:1212 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 6 14 theme boron 797:801 arg1 derivatives 803:813 boron derivatives 797:813 boron derivatives 797:813 Results showed that boron derivatives promote AI-2 activity in QS system. 35897636 1 15 theme bacterial 250:258 arg1 behavior 271:278 bacterial collective behavior 250:278 bacterial collective behavior 250:278 Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. 35897636 0 16 theme Sensing 101:107 arg1 Activity 130:137 Quorum Sensing System Autoinducer-2 Activity 94:137 Quorum Sensing System Autoinducer-2 Activity 94:137 Boron Derivatives Accelerate Biofilm Formation of Recombinant Escherichia coli via Increasing Quorum Sensing System Autoinducer-2 Activity. 35897636 10 17 theme genes 1313:1317 arg1 levels 1285:1290 the expression levels 1270:1290 the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes 1270:1369 Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. 35897636 5 18 theme stress 604:609 arg1 response 611:618 The stress response 600:618 The stress response of biofilm formation to boron 600:648 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 11 19 theme expression 1458:1467 arg1 levels 1469:1474 the expression levels 1454:1474 the expression levels of biofilm-related genes 1454:1499 These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli. 35897636 1 20 theme collective 260:269 arg1 behavior 271:278 bacterial collective behavior 250:278 bacterial collective behavior 250:278 Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. 35897636 10 21 theme biofilm 1295:1301 arg1 genes 1313:1317 biofilm formation genes 1295:1317 biofilm formation genes 1295:1317 Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. 35897636 10 22 theme flagellar 1346:1354 arg1 genes 1365:1369 flagellar movement genes 1346:1369 flagellar movement genes 1346:1369 Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. 35897636 4 23 theme biofilm 581:587 arg1 formation 589:597 biofilm formation 581:597 biofilm formation 581:597 This study screened different boron derivatives to explore their effect on biofilm formation. 35897636 0 24 theme Autoinducer-2 116:128 arg1 Activity 130:137 Quorum Sensing System Autoinducer-2 Activity 94:137 Quorum Sensing System Autoinducer-2 Activity 94:137 Boron Derivatives Accelerate Biofilm Formation of Recombinant Escherichia coli via Increasing Quorum Sensing System Autoinducer-2 Activity. 35897636 5 25 theme biofilm 623:629 arg1 formation 631:639 biofilm formation 623:639 biofilm formation 623:639 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 10 26 theme formation 1303:1311 arg1 genes 1313:1317 biofilm formation genes 1295:1317 biofilm formation genes 1295:1317 Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. 35897636 1 27 theme AI-2 189:192 arg1 synthesis 195:203 autoinducer-2 (AI-2) synthesis 174:203 autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system 174:233 Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. 35897636 10 28 theme genes 1335:1339 arg1 levels 1285:1290 the expression levels 1270:1290 the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes 1270:1369 Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. 35897636 11 29 theme EPS 1556:1558 arg1 secretion 1560:1568 EPS secretion 1556:1568 EPS secretion in E. coli 1556:1579 These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli. 35897636 5 30 theme formation 631:639 arg1 response 611:618 The stress response 600:618 The stress response of biofilm formation to boron 600:648 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 9 31 theme AI-2 1117:1120 arg1 Meanwhile 1106:1114 Meanwhile 1106:1114 Meanwhile 1106:1114 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 9 31 theme AI-2 1117:1120 arg1 activity 1122:1129 AI-2 activity 1117:1129 AI-2 activity 1117:1129 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 0 32 theme Boron 0:4 arg1 Derivatives 6:16 Boron Derivatives 0:16 Boron Derivatives 0:16 Boron Derivatives Accelerate Biofilm Formation of Recombinant Escherichia coli via Increasing Quorum Sensing System Autoinducer-2 Activity. 35897636 7 33 with treatment 857:865 arg1 H3BO3 872:876 H3BO3 872:876 H3BO3 (0.6 mM) 872:885 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 7 33 with treatment 857:865 arg1 mM 883:884 0.6 mM 879:884 0.6 mM 879:884 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 7 34 theme AI-2 892:895 arg1 activity 897:904 the AI-2 activity 888:904 the AI-2 activity 888:904 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 9 35 with correlation 1144:1154 arg1 protein 1181:1187 protein 1181:1187 protein 1181:1187 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 9 35 with correlation 1144:1154 arg1 polysaccharides 1161:1175 polysaccharides 1161:1175 polysaccharides 1161:1175 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 3 36 theme biofilm 415:421 arg1 formation 423:431 biofilm formation 415:431 biofilm formation 415:431 However, it is unclear how boron affects biofilm formation in E. coli, particularly recombinant E. coli with intracellular enzymes. 35897636 0 37 theme Biofilm 29:35 arg1 Formation 37:45 Biofilm Formation 29:45 Biofilm Formation of Recombinant Escherichia coli 29:77 Boron Derivatives Accelerate Biofilm Formation of Recombinant Escherichia coli via Increasing Quorum Sensing System Autoinducer-2 Activity. 35897636 5 38 theme extracellular 694:706 arg1 EPS 730:732 EPS 730:732 EPS 730:732 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 5 38 theme extracellular 694:706 arg1 substances 718:727 extracellular polymeric substances 694:727 extracellular polymeric substances (EPS) composition 694:745 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 11 39 theme biofilm 1420:1426 arg1 formation 1428:1436 biofilm formation 1420:1436 biofilm formation 1420:1436 These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli. 35897636 10 40 theme genes 1365:1369 arg1 levels 1285:1290 the expression levels 1270:1290 the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes 1270:1369 Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. 35897636 7 41 theme NaBO2 1006:1010 arg1 > 1012:1014 NaBO2 > 1006:1014 NaBO2 > 1006:1014 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 5 42 theme polymeric 708:716 arg1 EPS 730:732 EPS 730:732 EPS 730:732 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 5 42 theme polymeric 708:716 arg1 substances 718:727 extracellular polymeric substances 694:727 extracellular polymeric substances (EPS) composition 694:745 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 2 43 theme living 286:291 arg1 biocatalyst 293:303 a living biocatalyst 284:303 a living biocatalyst 284:303 As a living biocatalyst, biofilms can stably catalyze the activity of intracellular enzymes. 35897636 2 43 theme living 286:291 arg1 activity 339:346 the activity 335:346 the activity of intracellular enzymes 335:371 As a living biocatalyst, biofilms can stably catalyze the activity of intracellular enzymes. 35897636 1 44 theme quorum 208:213 arg1 QS 224:225 QS 224:225 QS 224:225 Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. 35897636 1 44 theme quorum 208:213 arg1 sensing 215:221 quorum sensing 208:221 quorum sensing (QS) system 208:233 Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. 35897636 7 45 from biofilms 973:980 arg1 > 1001:1003 the order H3BO3 > 985:1003 the order H3BO3 > 985:1003 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 5 46 theme substances 718:727 arg1 composition 735:745 extracellular polymeric substances (EPS) composition 694:745 extracellular polymeric substances (EPS) composition 694:745 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 5 46 theme substances 718:727 arg1 activity 684:691 AI-2 activity 679:691 AI-2 activity 679:691 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 9 47 theme linear 1137:1142 arg1 correlation 1144:1154 a linear correlation 1135:1154 a linear correlation with polysaccharides and protein of EPS 1135:1194 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 1 48 theme sensing 215:221 arg1 system 228:233 quorum sensing (QS) system 208:233 quorum sensing (QS) system 208:233 Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. 35897636 10 49 theme movement 1356:1363 arg1 genes 1365:1369 flagellar movement genes 1346:1369 flagellar movement genes 1346:1369 Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. 35897636 11 50 from secretion 1560:1568 arg1 coli 1576:1579 E. coli 1573:1579 E. coli 1573:1579 These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli. 35897636 11 51 theme genes 1495:1499 arg1 levels 1469:1474 the expression levels 1454:1474 the expression levels of biofilm-related genes 1454:1499 These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli. 35897636 4 52 from effect 571:576 arg1 formation 589:597 biofilm formation 581:597 biofilm formation 581:597 This study screened different boron derivatives to explore their effect on biofilm formation. 35897636 5 53 theme expression 753:762 arg1 activity 684:691 AI-2 activity 679:691 AI-2 activity 679:691 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 5 53 theme expression 753:762 arg1 levels 764:769 gene expression levels 748:769 gene expression levels 748:769 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 4 54 theme boron 536:540 arg1 derivatives 542:552 different boron derivatives 526:552 different boron derivatives 526:552 This study screened different boron derivatives to explore their effect on biofilm formation. 35897636 5 55 theme AI-2 679:682 arg1 activity 684:691 AI-2 activity 679:691 AI-2 activity 679:691 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 5 55 theme AI-2 679:682 arg1 composition 735:745 extracellular polymeric substances (EPS) composition 694:745 extracellular polymeric substances (EPS) composition 694:745 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 5 55 theme AI-2 679:682 arg1 etc 772:774 etc 772:774 etc 772:774 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 5 55 theme AI-2 679:682 arg1 levels 764:769 gene expression levels 748:769 gene expression levels 748:769 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 6 56 theme QS 840:841 arg1 system 843:848 QS system 840:848 QS system 840:848 Results showed that boron derivatives promote AI-2 activity in QS system. 35897636 7 57 theme biomass 965:971 arg1 biofilms 973:980 the biomass biofilms 961:980 the biomass biofilms in the order H3BO3 > 961:1003 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 4 58 theme different 526:534 arg1 derivatives 542:552 different boron derivatives 526:552 different boron derivatives 526:552 This study screened different boron derivatives to explore their effect on biofilm formation. 35897636 7 59 theme order 989:993 arg1 > 1001:1003 the order H3BO3 > 985:1003 the order H3BO3 > 985:1003 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 1 60 theme essential 152:160 arg1 element 162:168 an essential element 149:168 an essential element 149:168 Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. 35897636 1 60 theme essential 152:160 arg1 Boron 140:144 Boron 140:144 Boron 140:144 Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. 35897636 11 61 theme biofilm-related 1479:1493 arg1 genes 1495:1499 biofilm-related genes 1479:1499 biofilm-related genes 1479:1499 These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli. 35897636 7 62 theme H3BO3 995:999 arg1 > 1001:1003 the order H3BO3 > 985:1003 the order H3BO3 > 985:1003 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 11 63 theme QS 1516:1517 arg1 system 1519:1524 the QS system 1512:1524 the QS system AI-2 activity 1512:1538 These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli. 35897636 5 64 theme gene 748:751 arg1 activity 684:691 AI-2 activity 679:691 AI-2 activity 679:691 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 5 64 theme gene 748:751 arg1 levels 764:769 gene expression levels 748:769 gene expression levels 748:769 The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. 35897636 6 65 theme AI-2 823:826 arg1 activity 828:835 AI-2 activity 823:835 AI-2 activity 823:835 Results showed that boron derivatives promote AI-2 activity in QS system. 35897636 11 66 theme system 1519:1524 arg1 activity 1531:1538 the QS system AI-2 activity 1512:1538 the QS system AI-2 activity 1512:1538 These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli. 35897636 2 67 theme enzymes 365:371 arg1 biocatalyst 293:303 a living biocatalyst 284:303 a living biocatalyst 284:303 As a living biocatalyst, biofilms can stably catalyze the activity of intracellular enzymes. 35897636 2 67 theme enzymes 365:371 arg1 activity 339:346 the activity 335:346 the activity of intracellular enzymes 335:371 As a living biocatalyst, biofilms can stably catalyze the activity of intracellular enzymes. 35897636 1 68 theme system 228:233 arg1 synthesis 195:203 autoinducer-2 (AI-2) synthesis 174:203 autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system 174:233 Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. 35897636 0 69 theme coli 74:77 arg1 Formation 37:45 Biofilm Formation 29:45 Biofilm Formation of Recombinant Escherichia coli 29:77 Boron Derivatives Accelerate Biofilm Formation of Recombinant Escherichia coli via Increasing Quorum Sensing System Autoinducer-2 Activity. 35897636 9 70 theme EPS 1192:1194 arg1 protein 1181:1187 protein 1181:1187 protein 1181:1187 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 9 70 theme EPS 1192:1194 arg1 polysaccharides 1161:1175 polysaccharides 1161:1175 polysaccharides 1161:1175 Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0-0.6 mM H3BO3 and NaBO2 (R2 > 0.8). 35897636 7 71 theme boron 933:937 arg1 derivatives 939:949 boron derivatives 933:949 boron derivatives 933:949 After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. 35897636 2 72 theme intracellular 351:363 arg1 enzymes 365:371 intracellular enzymes 351:371 intracellular enzymes 351:371 As a living biocatalyst, biofilms can stably catalyze the activity of intracellular enzymes. 35306726 3 0 theme Engineering 310:320 arg1 attempts 322:329 Engineering attempts 310:329 Engineering attempts aiming to increase soybean seed oil 310:365 Engineering attempts aiming to increase soybean seed oil presented different degrees of success that varied with the genetic design and the specific variety considered. 35306726 9 1 theme AtWRI1 1276:1281 arg1 targets 1283:1289 Novel putative AtWRI1 targets 1261:1289 Novel putative AtWRI1 targets 1261:1289 Novel putative AtWRI1 targets, presenting an AW-box in the upstream region of the genes, were identified by comparison with an event that harbours only AtWRI1. 35306726 10 2 theme FA 1519:1520 arg1 starch 1550:1555 starch 1550:1555 starch 1550:1555 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 10 2 theme FA 1519:1520 arg1 polysaccharides 1571:1585 cell wall polysaccharides 1561:1585 cell wall polysaccharides 1561:1585 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 10 2 theme FA 1519:1520 arg1 pathways 1532:1539 FA competing pathways 1519:1539 FA competing pathways 1519:1539 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 10 3 theme sugar 1484:1488 arg1 phosphates 1490:1499 sugar phosphates 1484:1499 sugar phosphates 1484:1499 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 1 4 theme consumed 142:149 arg1 worldwide 166:174 the most consumed vegetable oils worldwide 133:174 the most consumed vegetable oils worldwide 133:174 Soybean oil is one of the most consumed vegetable oils worldwide. 35306726 4 5 theme successful 579:588 arg1 approaches 590:599 successful approaches 579:599 successful approaches 579:599 Understanding the embryo's responses to the genetic modifications introduced, is a critical step to successful approaches. 35306726 0 6 theme oil 78:80 arg1 metabolism 99:108 oil and carbohydrate metabolism 78:108 metabolism 99:108 Expression of AtWRI1 and AtDGAT1 during soybean embryo development influences oil and carbohydrate metabolism. 35306726 8 7 theme genes 1202:1206 arg1 down-regulation 1098:1112 a down-regulation 1096:1112 a down-regulation of genes putatively encoding for oil body packaging proteins 1096:1173 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 8 7 theme genes 1202:1206 arg1 induction 1189:1197 a strong induction 1180:1197 a strong induction of genes annotated as lipases and FA biosynthesis inhibitors 1180:1258 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 1 8 theme vegetable 151:159 arg1 worldwide 166:174 the most consumed vegetable oils worldwide 133:174 the most consumed vegetable oils worldwide 133:174 Soybean oil is one of the most consumed vegetable oils worldwide. 35306726 7 9 theme total 973:977 arg1 content 982:988 total FA content 973:988 total FA content 973:988 The events expressing these genes in the embryo did not show an increase in total FA content, but they responded with changes in the oil and carbohydrate composition. 35306726 3 10 theme seed 358:361 arg1 oil 363:365 soybean seed oil 350:365 soybean seed oil 350:365 Engineering attempts aiming to increase soybean seed oil presented different degrees of success that varied with the genetic design and the specific variety considered. 35306726 10 11 theme oil 1623:1625 arg1 accumulation 1627:1638 oil accumulation 1623:1638 oil accumulation 1623:1638 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 2 12 from improvement 185:195 arg1 seeds 221:225 seeds 221:225 seeds 221:225 Genetic improvement of its concentration in seeds has been historically pursued due to its direct association with its market value. 35306726 4 13 dep step 571:574 arg1 Understanding 479:491 Understanding 479:491 Understanding the embryo's responses to the genetic modifications introduced 479:554 Understanding the embryo's responses to the genetic modifications introduced, is a critical step to successful approaches. 35306726 9 14 with comparison 1369:1378 arg1 event 1388:1392 an event 1385:1392 an event that harbours only AtWRI1 1385:1418 Novel putative AtWRI1 targets, presenting an AW-box in the upstream region of the genes, were identified by comparison with an event that harbours only AtWRI1. 35306726 9 15 theme genes 1343:1347 arg1 region 1329:1334 the upstream region 1316:1334 the upstream region of the genes 1316:1347 Novel putative AtWRI1 targets, presenting an AW-box in the upstream region of the genes, were identified by comparison with an event that harbours only AtWRI1. 35306726 8 16 theme genes 1117:1121 arg1 down-regulation 1098:1112 a down-regulation 1096:1112 a down-regulation of genes putatively encoding for oil body packaging proteins 1096:1173 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 8 16 theme genes 1117:1121 arg1 induction 1189:1197 a strong induction 1180:1197 a strong induction of genes annotated as lipases and FA biosynthesis inhibitors 1180:1258 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 6 17 theme biosynthesis 883:894 arg1 step 857:860 the final and rate-limiting step 829:860 step 857:860 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 10 18 used used 1510:1513 arg2 carbon 1472:1477 carbon 1472:1477 carbon from sugar phosphates 1472:1499 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 2 19 theme direct 268:273 arg1 association 275:285 its direct association 264:285 its direct association with its market value 264:307 Genetic improvement of its concentration in seeds has been historically pursued due to its direct association with its market value. 35306726 8 20 theme FA 1233:1234 arg1 inhibitors 1249:1258 FA biosynthesis inhibitors 1233:1258 FA biosynthesis inhibitors 1233:1258 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 1 21 theme oils 161:164 arg1 worldwide 166:174 the most consumed vegetable oils worldwide 133:174 the most consumed vegetable oils worldwide 133:174 Soybean oil is one of the most consumed vegetable oils worldwide. 35306726 3 22 theme soybean 350:356 arg1 oil 363:365 soybean seed oil 350:365 soybean seed oil 350:365 Engineering attempts aiming to increase soybean seed oil presented different degrees of success that varied with the genetic design and the specific variety considered. 35306726 6 23 theme triacylglycerides 865:881 arg1 biosynthesis 883:894 triacylglycerides biosynthesis 865:894 triacylglycerides biosynthesis 865:894 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 5 24 theme metabolic 620:628 arg1 responses 650:658 the metabolic and transcriptional responses 616:658 the metabolic and transcriptional responses to AtWRI1 and AtDGAT1 expression in soybean seeds 616:708 In this work, the metabolic and transcriptional responses to AtWRI1 and AtDGAT1 expression in soybean seeds were evaluated. 35306726 6 25 theme biosynthesis 774:785 arg1 AtWRI1 726:731 AtWRI1 726:731 AtWRI1 726:731 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 6 25 theme biosynthesis 774:785 arg1 regulator 745:753 a master regulator 736:753 a master regulator of fatty acid (FA) biosynthesis 736:785 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 10 26 theme cell 1561:1564 arg1 polysaccharides 1571:1585 cell wall polysaccharides 1561:1585 cell wall polysaccharides 1561:1585 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 1 27 theme worldwide 166:174 arg1 one 126:128 one 126:128 one 126:128 Soybean oil is one of the most consumed vegetable oils worldwide. 35306726 1 27 theme worldwide 166:174 arg1 worldwide 166:174 the most consumed vegetable oils worldwide 133:174 the most consumed vegetable oils worldwide 133:174 Soybean oil is one of the most consumed vegetable oils worldwide. 35306726 9 28 from AW-box 1306:1311 arg1 region 1329:1334 the upstream region 1316:1334 the upstream region of the genes 1316:1347 Novel putative AtWRI1 targets, presenting an AW-box in the upstream region of the genes, were identified by comparison with an event that harbours only AtWRI1. 35306726 11 29 theme natural 1757:1763 arg1 restriction 1765:1775 the embryo's natural restriction 1744:1775 the embryo's natural restriction to uncontrolled seed lipid increase 1744:1811 These results allowed the identification of key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase. 35306726 10 30 theme targeted 1429:1436 arg1 analysis 1451:1458 targeted metabolomics analysis 1429:1458 targeted metabolomics analysis 1429:1458 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 0 31 theme carbohydrate 86:97 arg1 metabolism 99:108 oil and carbohydrate metabolism 78:108 metabolism 99:108 Expression of AtWRI1 and AtDGAT1 during soybean embryo development influences oil and carbohydrate metabolism. 35306726 9 32 theme upstream 1320:1327 arg1 region 1329:1334 the upstream region 1316:1334 the upstream region of the genes 1316:1347 Novel putative AtWRI1 targets, presenting an AW-box in the upstream region of the genes, were identified by comparison with an event that harbours only AtWRI1. 35306726 5 33 theme transcriptional 634:648 arg1 responses 650:658 the metabolic and transcriptional responses 616:658 the metabolic and transcriptional responses to AtWRI1 and AtDGAT1 expression in soybean seeds 616:708 In this work, the metabolic and transcriptional responses to AtWRI1 and AtDGAT1 expression in soybean seeds were evaluated. 35306726 11 34 theme processes 1698:1706 arg1 identification 1667:1680 the identification 1663:1680 the identification of key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase 1663:1811 These results allowed the identification of key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase. 35306726 3 35 theme genetic 427:433 arg1 design 435:440 the genetic design 423:440 the genetic design 423:440 Engineering attempts aiming to increase soybean seed oil presented different degrees of success that varied with the genetic design and the specific variety considered. 35306726 8 36 theme strong 1182:1187 arg1 induction 1189:1197 a strong induction 1180:1197 a strong induction of genes annotated as lipases and FA biosynthesis inhibitors 1180:1258 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 8 37 theme packaging 1156:1164 arg1 proteins 1166:1173 oil body packaging proteins 1147:1173 oil body packaging proteins 1147:1173 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 9 38 theme only 1408:1411 arg1 AtWRI1 1413:1418 only AtWRI1 1408:1418 only AtWRI1 1408:1418 Novel putative AtWRI1 targets, presenting an AW-box in the upstream region of the genes, were identified by comparison with an event that harbours only AtWRI1. 35306726 2 39 theme market 296:301 arg1 value 303:307 its market value 292:307 its market value 292:307 Genetic improvement of its concentration in seeds has been historically pursued due to its direct association with its market value. 35306726 3 40 theme different 377:385 arg1 degrees 387:393 different degrees 377:393 different degrees of success that varied with the genetic design and the specific variety considered 377:476 Engineering attempts aiming to increase soybean seed oil presented different degrees of success that varied with the genetic design and the specific variety considered. 35306726 7 41 theme carbohydrate 1038:1049 arg1 composition 1051:1061 carbohydrate composition 1038:1061 carbohydrate composition 1038:1061 The events expressing these genes in the embryo did not show an increase in total FA content, but they responded with changes in the oil and carbohydrate composition. 35306726 2 42 theme Genetic 177:183 arg1 improvement 185:195 Genetic improvement 177:195 Genetic improvement of its concentration in seeds 177:225 Genetic improvement of its concentration in seeds has been historically pursued due to its direct association with its market value. 35306726 1 43 theme Soybean 111:117 arg1 oil 119:121 Soybean oil 111:121 Soybean oil 111:121 Soybean oil is one of the most consumed vegetable oils worldwide. 35306726 8 44 theme biosynthesis 1236:1247 arg1 inhibitors 1249:1258 FA biosynthesis inhibitors 1233:1258 FA biosynthesis inhibitors 1233:1258 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 10 45 from phosphates 1490:1499 arg1 carbon 1472:1477 carbon 1472:1477 carbon from sugar phosphates 1472:1499 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 4 46 theme critical 562:569 arg1 step 571:574 a critical step 560:574 a critical step to successful approaches 560:599 Understanding the embryo's responses to the genetic modifications introduced, is a critical step to successful approaches. 35306726 7 47 dep oil 1030:1032 arg1 the 1026:1028 the 1026:1028 the 1026:1028 The events expressing these genes in the embryo did not show an increase in total FA content, but they responded with changes in the oil and carbohydrate composition. 35306726 6 48 theme rate-limiting 843:855 arg1 step 857:860 the final and rate-limiting step 829:860 step 857:860 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 0 49 theme AtDGAT1 25:31 arg1 Expression 0:9 Expression 0:9 Expression of AtWRI1 and AtDGAT1 during soybean embryo development 0:65 Expression of AtWRI1 and AtDGAT1 during soybean embryo development influences oil and carbohydrate metabolism. 35306726 11 50 theme lipid 1798:1802 arg1 increase 1804:1811 uncontrolled seed lipid increase 1780:1811 uncontrolled seed lipid increase 1780:1811 These results allowed the identification of key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase. 35306726 8 51 theme Transcriptomic 1064:1077 arg1 studies 1079:1085 Transcriptomic studies 1064:1085 Transcriptomic studies 1064:1085 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 6 52 theme acid 764:767 arg1 biosynthesis 774:785 fatty acid (FA) biosynthesis 758:785 fatty acid (FA) biosynthesis 758:785 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 3 53 theme specific 450:457 arg1 variety 459:465 the specific variety 446:465 the specific variety considered 446:476 Engineering attempts aiming to increase soybean seed oil presented different degrees of success that varied with the genetic design and the specific variety considered. 35306726 0 54 theme embryo 48:53 arg1 development 55:65 soybean embryo development 40:65 soybean embryo development 40:65 Expression of AtWRI1 and AtDGAT1 during soybean embryo development influences oil and carbohydrate metabolism. 35306726 4 55 theme genetic 523:529 arg1 modifications 531:543 the genetic modifications 519:543 the genetic modifications introduced 519:554 Understanding the embryo's responses to the genetic modifications introduced, is a critical step to successful approaches. 35306726 5 56 theme AtDGAT1 674:680 arg1 expression 682:691 AtDGAT1 expression 674:691 AtDGAT1 expression 674:691 In this work, the metabolic and transcriptional responses to AtWRI1 and AtDGAT1 expression in soybean seeds were evaluated. 35306726 6 57 theme final 833:837 arg1 step 857:860 the final and rate-limiting step 829:860 step 857:860 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 6 58 theme fatty 758:762 arg1 FA 770:771 FA 770:771 FA 770:771 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 6 58 theme fatty 758:762 arg1 acid 764:767 fatty acid 758:767 fatty acid (FA) biosynthesis 758:785 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 0 59 theme soybean 40:46 arg1 development 55:65 soybean embryo development 40:65 soybean embryo development 40:65 Expression of AtWRI1 and AtDGAT1 during soybean embryo development influences oil and carbohydrate metabolism. 35306726 5 60 from responses 650:658 arg1 seeds 704:708 soybean seeds 696:708 soybean seeds 696:708 In this work, the metabolic and transcriptional responses to AtWRI1 and AtDGAT1 expression in soybean seeds were evaluated. 35306726 2 61 theme concentration 204:216 arg1 improvement 185:195 Genetic improvement 177:195 Genetic improvement of its concentration in seeds 177:225 Genetic improvement of its concentration in seeds has been historically pursued due to its direct association with its market value. 35306726 10 62 theme metabolomics 1438:1449 arg1 analysis 1451:1458 targeted metabolomics analysis 1429:1458 targeted metabolomics analysis 1429:1458 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 11 63 theme seed 1793:1796 arg1 increase 1804:1811 uncontrolled seed lipid increase 1780:1811 uncontrolled seed lipid increase 1780:1811 These results allowed the identification of key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase. 35306726 8 64 theme oil 1147:1149 arg1 proteins 1166:1173 oil body packaging proteins 1147:1173 oil body packaging proteins 1147:1173 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 11 65 theme cellular 1689:1696 arg1 processes 1698:1706 key cellular processes 1685:1706 key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase 1685:1811 These results allowed the identification of key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase. 35306726 8 66 theme body 1151:1154 arg1 proteins 1166:1173 oil body packaging proteins 1147:1173 oil body packaging proteins 1147:1173 Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. 35306726 5 67 theme soybean 696:702 arg1 seeds 704:708 soybean seeds 696:708 soybean seeds 696:708 In this work, the metabolic and transcriptional responses to AtWRI1 and AtDGAT1 expression in soybean seeds were evaluated. 35306726 11 68 theme key 1685:1687 arg1 processes 1698:1706 key cellular processes 1685:1706 key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase 1685:1811 These results allowed the identification of key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase. 35306726 10 69 from restriction 1608:1618 arg1 accumulation 1627:1638 oil accumulation 1623:1638 oil accumulation 1623:1638 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 6 70 theme master 738:743 arg1 AtWRI1 726:731 AtWRI1 726:731 AtWRI1 726:731 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 6 70 theme master 738:743 arg1 regulator 745:753 a master regulator 736:753 a master regulator of fatty acid (FA) biosynthesis 736:785 AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. 35306726 11 71 theme uncontrolled 1780:1791 arg1 increase 1804:1811 uncontrolled seed lipid increase 1780:1811 uncontrolled seed lipid increase 1780:1811 These results allowed the identification of key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase. 35306726 10 72 theme competing 1522:1530 arg1 starch 1550:1555 starch 1550:1555 starch 1550:1555 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 10 72 theme competing 1522:1530 arg1 polysaccharides 1571:1585 cell wall polysaccharides 1561:1585 cell wall polysaccharides 1561:1585 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 10 72 theme competing 1522:1530 arg1 pathways 1532:1539 FA competing pathways 1519:1539 FA competing pathways 1519:1539 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 9 73 theme Novel 1261:1265 arg1 targets 1283:1289 Novel putative AtWRI1 targets 1261:1289 Novel putative AtWRI1 targets 1261:1289 Novel putative AtWRI1 targets, presenting an AW-box in the upstream region of the genes, were identified by comparison with an event that harbours only AtWRI1. 35306726 7 74 theme FA 979:980 arg1 content 982:988 total FA content 973:988 total FA content 973:988 The events expressing these genes in the embryo did not show an increase in total FA content, but they responded with changes in the oil and carbohydrate composition. 35306726 7 75 from increase 961:968 arg1 content 982:988 total FA content 973:988 total FA content 973:988 The events expressing these genes in the embryo did not show an increase in total FA content, but they responded with changes in the oil and carbohydrate composition. 35306726 7 76 from changes 1015:1021 arg1 oil 1030:1032 oil 1030:1032 oil 1030:1032 The events expressing these genes in the embryo did not show an increase in total FA content, but they responded with changes in the oil and carbohydrate composition. 35306726 7 76 from changes 1015:1021 arg1 composition 1051:1061 carbohydrate composition 1038:1061 carbohydrate composition 1038:1061 The events expressing these genes in the embryo did not show an increase in total FA content, but they responded with changes in the oil and carbohydrate composition. 35306726 3 77 theme success 398:404 arg1 degrees 387:393 different degrees 377:393 different degrees of success that varied with the genetic design and the specific variety considered 377:476 Engineering attempts aiming to increase soybean seed oil presented different degrees of success that varied with the genetic design and the specific variety considered. 35306726 9 78 theme putative 1267:1274 arg1 targets 1283:1289 Novel putative AtWRI1 targets 1261:1289 Novel putative AtWRI1 targets 1261:1289 Novel putative AtWRI1 targets, presenting an AW-box in the upstream region of the genes, were identified by comparison with an event that harbours only AtWRI1. 35306726 0 79 theme AtWRI1 14:19 arg1 Expression 0:9 Expression 0:9 Expression of AtWRI1 and AtDGAT1 during soybean embryo development 0:65 Expression of AtWRI1 and AtDGAT1 during soybean embryo development influences oil and carbohydrate metabolism. 35306726 10 80 theme wall 1566:1569 arg1 polysaccharides 1571:1585 cell wall polysaccharides 1561:1585 cell wall polysaccharides 1561:1585 Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. 35306726 2 81 with association 275:285 arg1 value 303:307 its market value 292:307 its market value 292:307 Genetic improvement of its concentration in seeds has been historically pursued due to its direct association with its market value. 35171578 11 0 theme fecal 1805:1809 arg1 samples 1811:1817 fecal samples 1805:1817 fecal samples of human ulcerative colitis (UC) patients and UC mice 1805:1871 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 12 1 theme differential 1916:1927 arg1 monosaccharides 1929:1943 The differential monosaccharides 1912:1943 The differential monosaccharides determined in human feces 1912:1969 The differential monosaccharides determined in human feces provided a good diagnostic performance in distinguishing the UC patients from healthy individuals, showing potential for clinical application. 35171578 11 2 theme ulcerative 1828:1837 arg1 colitis 1839:1845 ulcerative colitis 1828:1845 human ulcerative colitis (UC) patients 1822:1859 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 11 2 theme ulcerative 1828:1837 arg1 UC 1848:1849 UC 1848:1849 UC 1848:1849 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 10 3 theme herbal 1575:1580 arg1 polysaccharides 1582:1596 herbal polysaccharides 1575:1596 herbal polysaccharides 1575:1596 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 2 4 theme high 326:329 arg1 hydrophilicities 331:346 their high hydrophilicities 320:346 their high hydrophilicities 320:346 Sensitive and accurate analyses of monosaccharides remain challenging because of their high hydrophilicities and poor ionization efficiencies. 35171578 4 5 theme derivatization 657:670 arg1 efficiency 672:681 higher derivatization efficiency 650:681 higher derivatization efficiency for monosaccharides 650:701 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. 35171578 5 6 theme monosaccharides 772:786 arg1 derivatization 754:767 The derivatization 750:767 The derivatization of monosaccharides 750:786 The derivatization of monosaccharides was readily achieved in an aqueous solution. 35171578 10 7 theme composition 1560:1570 arg1 change 1606:1611 the change 1602:1611 the change in monosaccharide levels in human cell lines under physiopathological conditions 1602:1692 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 10 7 theme composition 1560:1570 arg1 quantification 1523:1536 sensitive and accurate quantification 1500:1536 sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides 1500:1596 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 0 8 theme Chromatography 136:149 arg1 Spectrometry 163:174 Liquid Chromatography Tandem Mass Spectrometry 129:174 Liquid Chromatography Tandem Mass Spectrometry 129:174 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 2 9 theme ionization 357:366 arg1 efficiencies 368:379 poor ionization efficiencies 352:379 poor ionization efficiencies 352:379 Sensitive and accurate analyses of monosaccharides remain challenging because of their high hydrophilicities and poor ionization efficiencies. 35171578 0 10 theme Mass 158:161 arg1 Spectrometry 163:174 Liquid Chromatography Tandem Mass Spectrometry 129:174 Liquid Chromatography Tandem Mass Spectrometry 129:174 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 9 11 theme R2 1409:1410 arg1 linearity 1398:1406 good linearity 1393:1406 good linearity (R2 > 0.99) 1393:1418 With the paired derivatization strategy, the monosaccharides could be accurately quantified with good linearity (R2 > 0.99) and satisfactory accuracy (recoveries: 85-110%). 35171578 9 11 theme R2 1409:1410 arg1 > 1412:1412 R2 > 0.99 1409:1417 R2 > 0.99 1409:1417 With the paired derivatization strategy, the monosaccharides could be accurately quantified with good linearity (R2 > 0.99) and satisfactory accuracy (recoveries: 85-110%). 35171578 2 12 theme monosaccharides 274:288 arg1 analyses 262:269 Sensitive and accurate analyses 239:269 Sensitive and accurate analyses of monosaccharides 239:288 Sensitive and accurate analyses of monosaccharides remain challenging because of their high hydrophilicities and poor ionization efficiencies. 35171578 11 13 from levels 1772:1777 arg1 samples 1811:1817 fecal samples 1805:1817 fecal samples of human ulcerative colitis (UC) patients and UC mice 1805:1871 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 3 14 with approach 425:432 arg1 hydroxylamines 451:464 H/D-labeled hydroxylamines 439:464 H/D-labeled hydroxylamines 439:464 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 5 15 theme aqueous 815:821 arg1 solution 823:830 an aqueous solution 812:830 an aqueous solution 812:830 The derivatization of monosaccharides was readily achieved in an aqueous solution. 35171578 7 16 theme retention 1165:1173 arg1 time 1175:1178 retention time 1165:1178 retention time 1165:1178 As a result, 12 monosaccharides were rapidly detected by LC-MS/MS within 16 min with significant improvements in chromatographic separation and retention time. 35171578 10 17 from levels 1631:1636 arg1 lines 1652:1656 human cell lines 1641:1656 human cell lines under physiopathological conditions 1641:1692 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 11 18 theme respective 1891:1900 arg1 controls 1902:1909 their respective controls 1885:1909 their respective controls 1885:1909 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 0 19 theme Sensitive 75:83 arg1 Analysis 98:105 Sensitive and Accurate Analysis 75:105 Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry 75:174 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 3 20 theme monosaccharides 504:518 arg1 quantification 483:496 simultaneous quantification 470:496 simultaneous quantification of 12 monosaccharides 470:518 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 4 21 theme 4-Methoxybenzyl 585:599 arg1 4-MOBHA·HCl 630:640 4-MOBHA·HCl 630:640 4-MOBHA·HCl 630:640 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. 35171578 4 21 theme 4-Methoxybenzyl 585:599 arg1 hydrochloride 615:627 O-(4-Methoxybenzyl)hydroxylamine hydrochloride 582:627 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) 582:641 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. 35171578 0 22 theme Accurate 89:96 arg1 Analysis 98:105 Sensitive and Accurate Analysis 75:105 Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry 75:174 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 8 23 theme detection 1185:1193 arg1 sensitivity 1195:1205 The detection sensitivity 1181:1205 The detection sensitivity 1181:1205 The detection sensitivity increased by 83 to 1600-fold with limits of quantitation ranging from 0.25 to 3.00 fmol. 35171578 7 24 theme significant 1106:1116 arg1 improvements 1118:1129 significant improvements 1106:1129 significant improvements in chromatographic separation and retention time 1106:1178 As a result, 12 monosaccharides were rapidly detected by LC-MS/MS within 16 min with significant improvements in chromatographic separation and retention time. 35171578 1 25 theme important 198:206 arg1 roles 208:212 important roles 198:212 important roles 198:212 Monosaccharides play important roles in biological processes. 35171578 4 26 theme hydroxylamine 601:613 arg1 4-MOBHA·HCl 630:640 4-MOBHA·HCl 630:640 4-MOBHA·HCl 630:640 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. 35171578 4 26 theme hydroxylamine 601:613 arg1 hydrochloride 615:627 O-(4-Methoxybenzyl)hydroxylamine hydrochloride 582:627 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) 582:641 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. 35171578 3 27 theme paired 403:408 arg1 approach 425:432 a paired derivatization approach 401:432 a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides 401:518 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 7 28 located detected 1066:1073 arg2 monosaccharides 1037:1051 12 monosaccharides 1034:1051 12 monosaccharides 1034:1051 As a result, 12 monosaccharides were rapidly detected by LC-MS/MS within 16 min with significant improvements in chromatographic separation and retention time. 35171578 7 28 located detected 1066:1073 arg1 min 1097:1099 16 min 1094:1099 16 min with significant improvements in chromatographic separation and retention time 1094:1178 As a result, 12 monosaccharides were rapidly detected by LC-MS/MS within 16 min with significant improvements in chromatographic separation and retention time. 35171578 7 28 located detected 1066:1073 arg2 result 1026:1031 a result 1024:1031 a result 1024:1031 As a result, 12 monosaccharides were rapidly detected by LC-MS/MS within 16 min with significant improvements in chromatographic separation and retention time. 35171578 4 29 theme O- 582:583 arg1 4-MOBHA·HCl 630:640 4-MOBHA·HCl 630:640 4-MOBHA·HCl 630:640 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. 35171578 4 29 theme O- 582:583 arg1 hydrochloride 615:627 O-(4-Methoxybenzyl)hydroxylamine hydrochloride 582:627 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) 582:641 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. 35171578 10 30 theme monosaccharide 1616:1629 arg1 levels 1631:1636 monosaccharide levels 1616:1636 monosaccharide levels in human cell lines under physiopathological conditions 1616:1692 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 0 31 theme Paired 0:5 arg1 Derivatization 7:20 Paired Derivatization 0:20 Paired Derivatization 0:20 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 3 32 theme H/D-labeled 439:449 arg1 hydroxylamines 451:464 H/D-labeled hydroxylamines 439:464 H/D-labeled hydroxylamines 439:464 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 4 33 theme higher 650:655 arg1 efficiency 672:681 higher derivatization efficiency 650:681 higher derivatization efficiency for monosaccharides 650:701 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. 35171578 10 34 theme cell 1647:1650 arg1 lines 1652:1656 human cell lines 1641:1656 human cell lines under physiopathological conditions 1641:1692 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 11 35 theme UC 1865:1866 arg1 mice 1868:1871 UC mice 1865:1871 UC mice 1865:1871 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 3 36 theme mass 552:555 arg1 spectrometry 557:568 tandem mass spectrometry 545:568 liquid chromatography tandem mass spectrometry (LC-MS/MS) 523:579 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 3 36 theme mass 552:555 arg1 LC-MS/MS 571:578 LC-MS/MS 571:578 LC-MS/MS 571:578 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 0 37 theme H/D-Labeled 36:46 arg1 Reagents 62:69 H/D-Labeled Hydroxylamine Reagents 36:69 H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry 36:174 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 8 38 theme quantitation 1251:1262 arg1 limits 1241:1246 limits 1241:1246 limits of quantitation ranging from 0.25 to 3.00 fmol 1241:1293 The detection sensitivity increased by 83 to 1600-fold with limits of quantitation ranging from 0.25 to 3.00 fmol. 35171578 12 39 theme diagnostic 1987:1996 arg1 performance 1998:2008 a good diagnostic performance 1980:2008 a good diagnostic performance 1980:2008 The differential monosaccharides determined in human feces provided a good diagnostic performance in distinguishing the UC patients from healthy individuals, showing potential for clinical application. 35171578 11 40 theme patients 1852:1859 arg1 samples 1811:1817 fecal samples 1805:1817 fecal samples of human ulcerative colitis (UC) patients and UC mice 1805:1871 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 0 41 with Approach 22:29 arg1 Reagents 62:69 H/D-Labeled Hydroxylamine Reagents 36:69 H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry 36:174 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 6 42 theme complex 996:1002 arg1 analysis 1011:1018 complex matrix analysis 996:1018 complex matrix analysis 996:1018 Furthermore, the deuterium-labeled isotope reagent, d3-4-MOBHA·HCl, was newly synthesized to stably label monosaccharides to improve its accuracy and precision in complex matrix analysis. 35171578 12 43 theme UC 2032:2033 arg1 patients 2035:2042 the UC patients 2028:2042 the UC patients 2028:2042 The differential monosaccharides determined in human feces provided a good diagnostic performance in distinguishing the UC patients from healthy individuals, showing potential for clinical application. 35171578 4 44 theme other 719:723 arg1 analogues 739:747 six other hydroxylamine analogues 715:747 six other hydroxylamine analogues 715:747 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. 35171578 10 45 theme sensitive 1500:1508 arg1 quantification 1523:1536 sensitive and accurate quantification 1500:1536 sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides 1500:1596 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 11 46 theme human 1822:1826 arg1 patients 1852:1859 human ulcerative colitis (UC) patients 1822:1859 human ulcerative colitis (UC) patients 1822:1859 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 6 47 theme isotope 868:874 arg1 d3-4-MOBHA·HCl 885:898 d3-4-MOBHA·HCl 885:898 d3-4-MOBHA·HCl 885:898 Furthermore, the deuterium-labeled isotope reagent, d3-4-MOBHA·HCl, was newly synthesized to stably label monosaccharides to improve its accuracy and precision in complex matrix analysis. 35171578 6 47 theme isotope 868:874 arg1 reagent 876:882 the deuterium-labeled isotope reagent 846:882 the deuterium-labeled isotope reagent 846:882 Furthermore, the deuterium-labeled isotope reagent, d3-4-MOBHA·HCl, was newly synthesized to stably label monosaccharides to improve its accuracy and precision in complex matrix analysis. 35171578 11 48 theme developed 1717:1725 arg1 able 1738:1741 able 1738:1741 able 1738:1741 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 11 48 theme developed 1717:1725 arg1 method 1727:1732 the developed method 1713:1732 the developed method 1713:1732 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 2 49 theme poor 352:355 arg1 efficiencies 368:379 poor ionization efficiencies 352:379 poor ionization efficiencies 352:379 Sensitive and accurate analyses of monosaccharides remain challenging because of their high hydrophilicities and poor ionization efficiencies. 35171578 10 50 theme accurate 1514:1521 arg1 quantification 1523:1536 sensitive and accurate quantification 1500:1536 sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides 1500:1596 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 1 51 theme biological 217:226 arg1 processes 228:236 biological processes 217:236 biological processes 217:236 Monosaccharides play important roles in biological processes. 35171578 8 52 dep 3.00 1285:1288 arg1 to 1282:1283 to 1282:1283 to 1282:1283 The detection sensitivity increased by 83 to 1600-fold with limits of quantitation ranging from 0.25 to 3.00 fmol. 35171578 11 53 theme colitis 1839:1845 arg1 patients 1852:1859 human ulcerative colitis (UC) patients 1822:1859 human ulcerative colitis (UC) patients 1822:1859 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 11 54 from monosaccharides 1786:1800 arg1 samples 1811:1817 fecal samples 1805:1817 fecal samples of human ulcerative colitis (UC) patients and UC mice 1805:1871 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 0 55 theme Tandem 151:156 arg1 Spectrometry 163:174 Liquid Chromatography Tandem Mass Spectrometry 129:174 Liquid Chromatography Tandem Mass Spectrometry 129:174 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 9 56 theme good 1393:1396 arg1 linearity 1398:1406 good linearity 1393:1406 good linearity (R2 > 0.99) 1393:1418 With the paired derivatization strategy, the monosaccharides could be accurately quantified with good linearity (R2 > 0.99) and satisfactory accuracy (recoveries: 85-110%). 35171578 9 56 theme good 1393:1396 arg1 > 1412:1412 R2 > 0.99 1409:1417 R2 > 0.99 1409:1417 With the paired derivatization strategy, the monosaccharides could be accurately quantified with good linearity (R2 > 0.99) and satisfactory accuracy (recoveries: 85-110%). 35171578 10 57 from change 1606:1611 arg1 levels 1631:1636 monosaccharide levels 1616:1636 monosaccharide levels in human cell lines under physiopathological conditions 1616:1692 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 7 58 with min 1097:1099 arg1 improvements 1118:1129 significant improvements 1106:1129 significant improvements in chromatographic separation and retention time 1106:1178 As a result, 12 monosaccharides were rapidly detected by LC-MS/MS within 16 min with significant improvements in chromatographic separation and retention time. 35171578 10 59 theme monosaccharide 1545:1558 arg1 composition 1560:1570 the monosaccharide composition 1541:1570 the monosaccharide composition of herbal polysaccharides 1541:1596 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 9 60 theme satisfactory 1424:1435 arg1 recoveries 1447:1456 recoveries 1447:1456 recoveries 1447:1456 With the paired derivatization strategy, the monosaccharides could be accurately quantified with good linearity (R2 > 0.99) and satisfactory accuracy (recoveries: 85-110%). 35171578 9 60 theme satisfactory 1424:1435 arg1 accuracy 1437:1444 satisfactory accuracy 1424:1444 satisfactory accuracy (recoveries: 85-110%) 1424:1466 With the paired derivatization strategy, the monosaccharides could be accurately quantified with good linearity (R2 > 0.99) and satisfactory accuracy (recoveries: 85-110%). 35171578 7 61 theme chromatographic 1134:1148 arg1 separation 1150:1159 chromatographic separation 1134:1159 chromatographic separation 1134:1159 As a result, 12 monosaccharides were rapidly detected by LC-MS/MS within 16 min with significant improvements in chromatographic separation and retention time. 35171578 2 62 theme Sensitive 239:247 arg1 analyses 262:269 Sensitive and accurate analyses 239:269 Sensitive and accurate analyses of monosaccharides 239:288 Sensitive and accurate analyses of monosaccharides remain challenging because of their high hydrophilicities and poor ionization efficiencies. 35171578 7 63 from improvements 1118:1129 arg1 separation 1150:1159 chromatographic separation 1134:1159 chromatographic separation 1134:1159 As a result, 12 monosaccharides were rapidly detected by LC-MS/MS within 16 min with significant improvements in chromatographic separation and retention time. 35171578 7 63 from improvements 1118:1129 arg1 time 1175:1178 retention time 1165:1178 retention time 1165:1178 As a result, 12 monosaccharides were rapidly detected by LC-MS/MS within 16 min with significant improvements in chromatographic separation and retention time. 35171578 0 64 theme Monosaccharides 110:124 arg1 Analysis 98:105 Sensitive and Accurate Analysis 75:105 Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry 75:174 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 9 65 theme paired 1305:1310 arg1 strategy 1327:1334 the paired derivatization strategy 1301:1334 the paired derivatization strategy 1301:1334 With the paired derivatization strategy, the monosaccharides could be accurately quantified with good linearity (R2 > 0.99) and satisfactory accuracy (recoveries: 85-110%). 35171578 10 66 theme polysaccharides 1582:1596 arg1 composition 1560:1570 the monosaccharide composition 1541:1570 the monosaccharide composition of herbal polysaccharides 1541:1596 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 6 67 theme deuterium-labeled 850:866 arg1 d3-4-MOBHA·HCl 885:898 d3-4-MOBHA·HCl 885:898 d3-4-MOBHA·HCl 885:898 Furthermore, the deuterium-labeled isotope reagent, d3-4-MOBHA·HCl, was newly synthesized to stably label monosaccharides to improve its accuracy and precision in complex matrix analysis. 35171578 6 67 theme deuterium-labeled 850:866 arg1 reagent 876:882 the deuterium-labeled isotope reagent 846:882 the deuterium-labeled isotope reagent 846:882 Furthermore, the deuterium-labeled isotope reagent, d3-4-MOBHA·HCl, was newly synthesized to stably label monosaccharides to improve its accuracy and precision in complex matrix analysis. 35171578 0 68 theme Liquid 129:134 arg1 Spectrometry 163:174 Liquid Chromatography Tandem Mass Spectrometry 129:174 Liquid Chromatography Tandem Mass Spectrometry 129:174 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 3 69 theme derivatization 410:423 arg1 approach 425:432 a paired derivatization approach 401:432 a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides 401:518 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 3 70 theme tandem 545:550 arg1 spectrometry 557:568 tandem mass spectrometry 545:568 liquid chromatography tandem mass spectrometry (LC-MS/MS) 523:579 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 3 70 theme tandem 545:550 arg1 LC-MS/MS 571:578 LC-MS/MS 571:578 LC-MS/MS 571:578 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 12 71 theme clinical 2092:2099 arg1 application 2101:2111 clinical application 2092:2111 clinical application 2092:2111 The differential monosaccharides determined in human feces provided a good diagnostic performance in distinguishing the UC patients from healthy individuals, showing potential for clinical application. 35171578 3 72 theme simultaneous 470:481 arg1 quantification 483:496 simultaneous quantification 470:496 simultaneous quantification of 12 monosaccharides 470:518 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 9 73 dep recoveries 1447:1456 arg1 % 1465:1465 85-110% 1459:1465 85-110% 1459:1465 With the paired derivatization strategy, the monosaccharides could be accurately quantified with good linearity (R2 > 0.99) and satisfactory accuracy (recoveries: 85-110%). 35171578 3 74 theme liquid 523:528 arg1 chromatography 530:543 liquid chromatography tandem mass spectrometry (LC-MS/MS) 523:579 liquid chromatography tandem mass spectrometry (LC-MS/MS) 523:579 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 12 75 theme healthy 2049:2055 arg1 individuals 2057:2067 healthy individuals 2049:2067 healthy individuals 2049:2067 The differential monosaccharides determined in human feces provided a good diagnostic performance in distinguishing the UC patients from healthy individuals, showing potential for clinical application. 35171578 9 76 theme derivatization 1312:1325 arg1 strategy 1327:1334 the paired derivatization strategy 1301:1334 the paired derivatization strategy 1301:1334 With the paired derivatization strategy, the monosaccharides could be accurately quantified with good linearity (R2 > 0.99) and satisfactory accuracy (recoveries: 85-110%). 35171578 0 77 theme Hydroxylamine 48:60 arg1 Reagents 62:69 H/D-Labeled Hydroxylamine Reagents 36:69 H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry 36:174 Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry. 35171578 11 78 from samples 1811:1817 arg1 levels 1772:1777 the levels 1768:1777 the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice 1768:1871 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 10 79 theme human 1641:1645 arg1 lines 1652:1656 human cell lines 1641:1656 human cell lines under physiopathological conditions 1641:1692 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 6 80 theme matrix 1004:1009 arg1 analysis 1011:1018 complex matrix analysis 996:1018 complex matrix analysis 996:1018 Furthermore, the deuterium-labeled isotope reagent, d3-4-MOBHA·HCl, was newly synthesized to stably label monosaccharides to improve its accuracy and precision in complex matrix analysis. 35171578 3 81 dep chromatography 530:543 arg1 spectrometry 557:568 tandem mass spectrometry 545:568 liquid chromatography tandem mass spectrometry (LC-MS/MS) 523:579 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 3 81 dep chromatography 530:543 arg1 LC-MS/MS 571:578 LC-MS/MS 571:578 LC-MS/MS 571:578 Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). 35171578 12 82 theme good 1982:1985 arg1 performance 1998:2008 a good diagnostic performance 1980:2008 a good diagnostic performance 1980:2008 The differential monosaccharides determined in human feces provided a good diagnostic performance in distinguishing the UC patients from healthy individuals, showing potential for clinical application. 35171578 10 83 from quantification 1523:1536 arg1 levels 1631:1636 monosaccharide levels 1616:1636 monosaccharide levels in human cell lines under physiopathological conditions 1616:1692 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 2 84 theme accurate 253:260 arg1 analyses 262:269 Sensitive and accurate analyses 239:269 Sensitive and accurate analyses of monosaccharides 239:288 Sensitive and accurate analyses of monosaccharides remain challenging because of their high hydrophilicities and poor ionization efficiencies. 35171578 4 85 theme hydroxylamine 725:737 arg1 analogues 739:747 six other hydroxylamine analogues 715:747 six other hydroxylamine analogues 715:747 O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. 35171578 10 86 theme physiopathological 1664:1681 arg1 conditions 1683:1692 physiopathological conditions 1664:1692 physiopathological conditions 1664:1692 Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. 35171578 11 87 theme mice 1868:1871 arg1 samples 1811:1817 fecal samples 1805:1817 fecal samples of human ulcerative colitis (UC) patients and UC mice 1805:1871 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 11 88 theme monosaccharides 1786:1800 arg1 levels 1772:1777 the levels 1768:1777 the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice 1768:1871 More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. 35171578 12 89 theme human 1959:1963 arg1 feces 1965:1969 human feces 1959:1969 human feces 1959:1969 The differential monosaccharides determined in human feces provided a good diagnostic performance in distinguishing the UC patients from healthy individuals, showing potential for clinical application. 35171578 8 90 dep 1600-fold 1226:1234 arg1 to 1223:1224 to 1223:1224 to 1223:1224 The detection sensitivity increased by 83 to 1600-fold with limits of quantitation ranging from 0.25 to 3.00 fmol. 36830094 8 0 theme fruits 1096:1101 arg1 extracts 1080:1087 aqueous ethanolic extracts 1062:1087 aqueous ethanolic extracts of the fruits 1062:1101 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 1 theme responsible 1180:1190 arg1 compounds 1170:1178 the main compounds 1161:1178 the main compounds responsible for antioxidant activity 1161:1215 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 2 theme Fourier-transform 966:982 arg1 FTIR 1007:1010 FTIR 1007:1010 FTIR 1007:1010 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 2 theme Fourier-transform 966:982 arg1 spectroscopy 993:1004 Fourier-transform infrared spectroscopy 966:1004 Fourier-transform infrared spectroscopy (FTIR) 966:1011 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 3 used used 1017:1020 arg2 FTIR 1007:1010 FTIR 1007:1010 FTIR 1007:1010 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 3 used used 1017:1020 arg2 spectroscopy 993:1004 Fourier-transform infrared spectroscopy 966:1004 Fourier-transform infrared spectroscopy (FTIR) 966:1011 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 4 theme amounts 1141:1147 arg1 presence 1124:1131 the presence 1120:1131 the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides 1120:1262 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 7 5 theme antioxidant 900:910 arg1 activity 912:919 higher antioxidant activity 893:919 higher antioxidant activity 893:919 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 6 6 from genotype 700:707 arg1 components 624:633 the antioxidant components 608:633 the antioxidant components 608:633 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 6 6 from genotype 700:707 arg1 activity 651:658 antioxidant activity 639:658 antioxidant activity 639:658 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 6 6 from genotype 700:707 arg1 extracts 681:688 aqueous ethanolic extracts 663:688 aqueous ethanolic extracts from each genotype 663:707 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 5 7 theme tamarillo 548:556 arg1 genotypes 535:543 four genotypes 530:543 four genotypes of tamarillo 530:556 The present work aims to study the antioxidant activity of four genotypes of tamarillo. 36830094 6 8 theme chemical 567:574 arg1 assays 576:581 Several chemical assays 559:581 Several chemical assays 559:581 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 8 9 theme infrared 984:991 arg1 FTIR 1007:1010 FTIR 1007:1010 FTIR 1007:1010 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 9 theme infrared 984:991 arg1 spectroscopy 993:1004 Fourier-transform infrared spectroscopy 966:1004 Fourier-transform infrared spectroscopy (FTIR) 966:1011 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 6 10 theme extracts 681:688 arg1 components 624:633 the antioxidant components 608:633 the antioxidant components 608:633 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 6 10 theme extracts 681:688 arg1 activity 651:658 antioxidant activity 639:658 antioxidant activity 639:658 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 7 11 theme highest 810:816 arg1 contents 872:879 anthocyanin contents 860:879 anthocyanin contents 860:879 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 11 theme highest 810:816 arg1 flavonoids 844:853 flavonoids 844:853 flavonoids 844:853 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 11 theme highest 810:816 arg1 amount 818:823 the highest amount 806:823 the highest amount of total phenolic, flavonoids, and anthocyanin contents 806:879 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 12 theme higher 893:898 arg1 activity 912:919 higher antioxidant activity 893:919 higher antioxidant activity 893:919 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 6 13 theme ethanolic 671:679 arg1 extracts 681:688 aqueous ethanolic extracts 663:688 aqueous ethanolic extracts from each genotype 663:707 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 2 14 from crop 184:187 arg1 regions 200:206 several regions 192:206 several regions of the world 192:219 is a small tree cultivated as a fruit crop in several regions of the world. 36830094 9 15 theme fruits 1347:1352 arg1 importance 1323:1332 the potential nutraceutical importance 1295:1332 the potential nutraceutical importance of tamarillo fruits 1295:1352 The present results highlight the potential nutraceutical importance of tamarillo fruits. 36830094 6 16 theme aqueous 663:669 arg1 extracts 681:688 aqueous ethanolic extracts 663:688 aqueous ethanolic extracts from each genotype 663:707 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 8 17 theme main 1165:1168 arg1 compounds 1170:1178 the main compounds 1161:1178 the main compounds responsible for antioxidant activity 1161:1215 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 6 18 theme Several 559:565 arg1 assays 576:581 Several chemical assays 559:581 Several chemical assays 559:581 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 0 19 theme Antioxidant 0:10 arg1 Potential 12:20 Antioxidant Potential 0:20 Antioxidant Potential of Tamarillo 0:33 Antioxidant Potential of Tamarillo Fruits-Chemical and Infrared Spectroscopy Analysis. 36830094 9 20 theme present 1269:1275 arg1 results 1277:1283 The present results 1265:1283 The present results 1265:1283 The present results highlight the potential nutraceutical importance of tamarillo fruits. 36830094 7 21 theme contents 872:879 arg1 contents 872:879 anthocyanin contents 860:879 anthocyanin contents 860:879 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 21 theme contents 872:879 arg1 activity 912:919 higher antioxidant activity 893:919 higher antioxidant activity 893:919 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 21 theme contents 872:879 arg1 flavonoids 844:853 flavonoids 844:853 flavonoids 844:853 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 21 theme contents 872:879 arg1 amount 818:823 the highest amount 806:823 the highest amount of total phenolic, flavonoids, and anthocyanin contents 806:879 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 6 22 from components 624:633 arg1 genotype 700:707 each genotype 695:707 each genotype 695:707 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 8 23 theme extract 957:963 arg1 composition 938:948 the composition 934:948 the composition of the extract 934:963 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 3 24 theme health-beneficial 318:334 arg1 vitamins 362:369 vitamins 362:369 vitamins 362:369 Known for its sweet and sour taste, tamarillo fruits are very nutritious due to the presence of health-beneficial components such as fiber, vitamins, and antioxidants. 36830094 3 24 theme health-beneficial 318:334 arg1 components 336:345 health-beneficial components 318:345 health-beneficial components such as fiber, vitamins, and antioxidants 318:387 Known for its sweet and sour taste, tamarillo fruits are very nutritious due to the presence of health-beneficial components such as fiber, vitamins, and antioxidants. 36830094 3 24 theme health-beneficial 318:334 arg1 fiber 355:359 fiber 355:359 fiber 355:359 Known for its sweet and sour taste, tamarillo fruits are very nutritious due to the presence of health-beneficial components such as fiber, vitamins, and antioxidants. 36830094 3 24 theme health-beneficial 318:334 arg1 antioxidants 376:387 antioxidants 376:387 antioxidants 376:387 Known for its sweet and sour taste, tamarillo fruits are very nutritious due to the presence of health-beneficial components such as fiber, vitamins, and antioxidants. 36830094 8 25 theme triterpenoids 1230:1242 arg1 triterpenoids 1230:1242 triterpenoids 1230:1242 triterpenoids 1230:1242 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 25 theme triterpenoids 1230:1242 arg1 phenols 1152:1158 phenols 1152:1158 phenols (the main compounds responsible for antioxidant activity) 1152:1216 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 25 theme triterpenoids 1230:1242 arg1 amounts 1141:1147 high amounts 1136:1147 high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides 1136:1262 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 5 26 theme genotypes 535:543 arg1 activity 518:525 the antioxidant activity 502:525 the antioxidant activity of four genotypes of tamarillo 502:556 The present work aims to study the antioxidant activity of four genotypes of tamarillo. 36830094 6 27 from activity 651:658 arg1 genotype 700:707 each genotype 695:707 each genotype 695:707 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 6 28 theme antioxidant 639:649 arg1 activity 651:658 antioxidant activity 639:658 antioxidant activity 639:658 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 3 29 theme components 336:345 arg1 presence 306:313 the presence 302:313 the presence of health-beneficial components such as fiber, vitamins, and antioxidants 302:387 Known for its sweet and sour taste, tamarillo fruits are very nutritious due to the presence of health-beneficial components such as fiber, vitamins, and antioxidants. 36830094 4 30 theme nutritional 402:412 arg1 value 414:418 its nutritional value 398:418 its nutritional value 398:418 Despite its nutritional value, tamarillo remains poorly known in global markets. 36830094 0 31 dep Analysis 77:84 arg1 Potential 12:20 Antioxidant Potential 0:20 Antioxidant Potential of Tamarillo 0:33 Antioxidant Potential of Tamarillo Fruits-Chemical and Infrared Spectroscopy Analysis. 36830094 8 32 theme antioxidant 1196:1206 arg1 activity 1208:1215 antioxidant activity 1196:1215 antioxidant activity 1196:1215 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 33 theme phenols 1152:1158 arg1 triterpenoids 1230:1242 triterpenoids 1230:1242 triterpenoids 1230:1242 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 33 theme phenols 1152:1158 arg1 phenols 1152:1158 phenols 1152:1158 phenols (the main compounds responsible for antioxidant activity) 1152:1216 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 33 theme phenols 1152:1158 arg1 amounts 1141:1147 high amounts 1136:1147 high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides 1136:1262 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 34 theme important 1038:1046 arg1 components 1048:1057 important components 1038:1057 important components 1038:1057 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 7 35 theme interesting 774:784 arg1 results 786:792 the most interesting results 765:792 the most interesting results 765:792 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 0 36 theme Fruits-Chemical 35:49 arg1 Analysis 77:84 Fruits-Chemical and Infrared Spectroscopy Analysis 35:84 Fruits-Chemical and Infrared Spectroscopy Analysis 35:84 Antioxidant Potential of Tamarillo Fruits-Chemical and Infrared Spectroscopy Analysis. 36830094 9 37 theme potential 1299:1307 arg1 importance 1323:1332 the potential nutraceutical importance 1295:1332 the potential nutraceutical importance of tamarillo fruits 1295:1352 The present results highlight the potential nutraceutical importance of tamarillo fruits. 36830094 0 38 theme Tamarillo 25:33 arg1 Potential 12:20 Antioxidant Potential 0:20 Antioxidant Potential of Tamarillo 0:33 Antioxidant Potential of Tamarillo Fruits-Chemical and Infrared Spectroscopy Analysis. 36830094 0 39 theme Spectroscopy 64:75 arg1 Analysis 77:84 Fruits-Chemical and Infrared Spectroscopy Analysis 35:84 Fruits-Chemical and Infrared Spectroscopy Analysis 35:84 Antioxidant Potential of Tamarillo Fruits-Chemical and Infrared Spectroscopy Analysis. 36830094 7 40 theme red 744:746 arg1 genotype 732:739 the Mealhada genotype 719:739 the Mealhada genotype (a red cultivar) 719:756 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 40 theme red 744:746 arg1 cultivar 748:755 a red cultivar 742:755 a red cultivar 742:755 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 3 41 theme tamarillo 258:266 arg1 fruits 268:273 tamarillo fruits 258:273 tamarillo fruits 258:273 Known for its sweet and sour taste, tamarillo fruits are very nutritious due to the presence of health-beneficial components such as fiber, vitamins, and antioxidants. 36830094 2 42 theme small 151:155 arg1 tree 157:160 a small tree 149:160 a small tree cultivated as a fruit crop in several regions of the world 149:219 is a small tree cultivated as a fruit crop in several regions of the world. 36830094 0 43 theme Infrared 55:62 arg1 Analysis 77:84 Fruits-Chemical and Infrared Spectroscopy Analysis 35:84 Fruits-Chemical and Infrared Spectroscopy Analysis 35:84 Antioxidant Potential of Tamarillo Fruits-Chemical and Infrared Spectroscopy Analysis. 36830094 2 44 theme several 192:198 arg1 regions 200:206 several regions 192:206 several regions of the world 192:219 is a small tree cultivated as a fruit crop in several regions of the world. 36830094 1 45 theme Solanum 123:129 arg1 Cav 140:142 Solanum betaceum Cav. 123:143 Solanum betaceum Cav. 123:143 Native to South America, tamarillo (Solanum betaceum Cav.) 36830094 1 45 theme Solanum 123:129 arg1 tamarillo 112:120 tamarillo 112:120 tamarillo (Solanum betaceum Cav.) 112:144 Native to South America, tamarillo (Solanum betaceum Cav.) 36830094 6 46 theme antioxidant 612:622 arg1 components 624:633 the antioxidant components 608:633 the antioxidant components 608:633 Several chemical assays were performed to assess the antioxidant components and antioxidant activity of aqueous ethanolic extracts from each genotype. 36830094 8 47 theme ethanolic 1070:1078 arg1 extracts 1080:1087 aqueous ethanolic extracts 1062:1087 aqueous ethanolic extracts of the fruits 1062:1101 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 48 theme high 1136:1139 arg1 triterpenoids 1230:1242 triterpenoids 1230:1242 triterpenoids 1230:1242 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 48 theme high 1136:1139 arg1 phenols 1152:1158 phenols 1152:1158 phenols (the main compounds responsible for antioxidant activity) 1152:1216 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 8 48 theme high 1136:1139 arg1 amounts 1141:1147 high amounts 1136:1147 high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides 1136:1262 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 5 49 theme antioxidant 506:516 arg1 activity 518:525 the antioxidant activity 502:525 the antioxidant activity of four genotypes of tamarillo 502:556 The present work aims to study the antioxidant activity of four genotypes of tamarillo. 36830094 1 50 theme betaceum 131:138 arg1 Cav 140:142 Solanum betaceum Cav. 123:143 Solanum betaceum Cav. 123:143 Native to South America, tamarillo (Solanum betaceum Cav.) 36830094 1 50 theme betaceum 131:138 arg1 tamarillo 112:120 tamarillo 112:120 tamarillo (Solanum betaceum Cav.) 112:144 Native to South America, tamarillo (Solanum betaceum Cav.) 36830094 7 51 theme anthocyanin 860:870 arg1 contents 872:879 anthocyanin contents 860:879 anthocyanin contents 860:879 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 9 52 theme tamarillo 1337:1345 arg1 fruits 1347:1352 tamarillo fruits 1337:1352 tamarillo fruits 1337:1352 The present results highlight the potential nutraceutical importance of tamarillo fruits. 36830094 8 53 theme aqueous 1062:1068 arg1 extracts 1080:1087 aqueous ethanolic extracts 1062:1087 aqueous ethanolic extracts of the fruits 1062:1101 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 2 54 theme fruit 178:182 arg1 crop 184:187 a fruit crop 176:187 a fruit crop in several regions of the world 176:219 is a small tree cultivated as a fruit crop in several regions of the world. 36830094 7 55 theme flavonoids 844:853 arg1 contents 872:879 anthocyanin contents 860:879 anthocyanin contents 860:879 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 55 theme flavonoids 844:853 arg1 activity 912:919 higher antioxidant activity 893:919 higher antioxidant activity 893:919 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 55 theme flavonoids 844:853 arg1 flavonoids 844:853 flavonoids 844:853 flavonoids 844:853 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 55 theme flavonoids 844:853 arg1 amount 818:823 the highest amount 806:823 the highest amount of total phenolic, flavonoids, and anthocyanin contents 806:879 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 56 theme Mealhada 723:730 arg1 genotype 732:739 the Mealhada genotype 719:739 the Mealhada genotype (a red cultivar) 719:756 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 56 theme Mealhada 723:730 arg1 cultivar 748:755 a red cultivar 742:755 a red cultivar 742:755 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 7 57 theme total 828:832 arg1 flavonoids 844:853 flavonoids 844:853 flavonoids 844:853 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 5 58 theme present 475:481 arg1 work 483:486 The present work 471:486 The present work 471:486 The present work aims to study the antioxidant activity of four genotypes of tamarillo. 36830094 3 59 dep sweet 236:240 arg1 taste 251:255 taste 251:255 taste 251:255 Known for its sweet and sour taste, tamarillo fruits are very nutritious due to the presence of health-beneficial components such as fiber, vitamins, and antioxidants. 36830094 4 60 theme global 455:460 arg1 markets 462:468 global markets 455:468 global markets 455:468 Despite its nutritional value, tamarillo remains poorly known in global markets. 36830094 2 61 theme world 215:219 arg1 regions 200:206 several regions 192:206 several regions of the world 192:219 is a small tree cultivated as a fruit crop in several regions of the world. 36830094 8 62 dep phenols 1152:1158 arg1 compounds 1170:1178 the main compounds 1161:1178 the main compounds responsible for antioxidant activity 1161:1215 To evaluate the composition of the extract, Fourier-transform infrared spectroscopy (FTIR) was used to characterize important components in aqueous ethanolic extracts of the fruits, having revealed the presence of high amounts of phenols (the main compounds responsible for antioxidant activity), as well as triterpenoids and polysaccharides. 36830094 1 63 dep tamarillo 112:120 arg1 America 103:109 America 103:109 America 103:109 Native to South America, tamarillo (Solanum betaceum Cav.) 36830094 7 64 theme phenolic 834:841 arg1 flavonoids 844:853 flavonoids 844:853 flavonoids 844:853 Overall, the Mealhada genotype (a red cultivar) showed the most interesting results, displaying the highest amount of total phenolic, flavonoids, and anthocyanin contents, as well as higher antioxidant activity. 36830094 9 65 theme nutraceutical 1309:1321 arg1 importance 1323:1332 the potential nutraceutical importance 1295:1332 the potential nutraceutical importance of tamarillo fruits 1295:1352 The present results highlight the potential nutraceutical importance of tamarillo fruits. 36613350 0 0 theme Promoting 82:90 arg1 Ingredients 97:107 Health Promoting Food Ingredients 75:107 Health Promoting Food Ingredients 75:107 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 36613350 7 1 theme Staphylococcus 1088:1101 arg1 bacteria 1071:1078 Gram-positive bacteria 1057:1078 Gram-positive bacteria 1057:1078 Chicory HMWM revealed to be effective against Gram-positive bacteria, mainly Staphylococcus aureus and Bacillus cereus, although not so efficient as coffee. 36613350 8 2 dep activity 1218:1225 arg1 inhibition 1235:1244 inhibition 1235:1244 inhibition 1235:1244 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 8 2 dep activity 1218:1225 arg1 % 1230:1230 15% 1228:1230 15% of inhibition 1228:1244 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 9 3 theme antioxidant 1435:1445 arg1 diet 1447:1450 an antioxidant diet 1432:1450 an antioxidant diet 1432:1450 Thus, chicory melanoidins, when used as a food ingredient, may contribute to an antioxidant diet and to prevent diabetes, while increasing the protective effects against pathogenic bacteria. 36613350 8 4 theme α-glucosidase 1204:1216 arg1 activity 1218:1225 α-glucosidase activity 1204:1225 α-glucosidase activity (15% of inhibition) 1204:1245 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 6 5 dep scavenging 923:932 arg1 IC50 935:938 IC50 935:938 IC50 = 0.28 mg/mL 935:951 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 0 6 theme Health 75:80 arg1 Ingredients 97:107 Health Promoting Food Ingredients 75:107 Health Promoting Food Ingredients 75:107 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 36613350 6 7 theme condensed 847:855 arg1 g 879:879 0.9 g/100 g 869:879 0.9 g/100 g 869:879 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 7 theme condensed 847:855 arg1 g 895:895 5.8 g/100 g 885:895 5.8 g/100 g 885:895 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 7 theme condensed 847:855 arg1 structures 857:866 glycosidically linked and condensed structures 821:866 glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g) 821:896 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 8 dep eq/mg 1003:1007 arg1 ca. 988:990 ca. 988:990 ca. 988:990 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 9 theme in 907:908 arg1 scavenging 923:932 in vitro ABTS•+ scavenging 907:932 in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) 907:952 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 5 10 theme w/w 697:699 arg1 polysaccharides 674:688 fructose-rich polysaccharides 660:688 fructose-rich polysaccharides (18.7% w/w) 660:700 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 10 theme w/w 697:699 arg1 % 695:695 18.7% w/w 691:699 18.7% w/w 691:699 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 4 11 theme biological 507:516 arg1 activity 518:525 biological activity 507:525 biological activity 507:525 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 5 12 theme chicory 595:601 arg1 HMWM 603:606 The chicory HMWM 591:606 The chicory HMWM 591:606 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 7 13 dep not 1140:1142 arg1 efficient 1147:1155 efficient 1147:1155 efficient 1147:1155 Chicory HMWM revealed to be effective against Gram-positive bacteria, mainly Staphylococcus aureus and Bacillus cereus, although not so efficient as coffee. 36613350 0 14 theme Food 92:95 arg1 Ingredients 97:107 Health Promoting Food Ingredients 75:107 Health Promoting Food Ingredients 75:107 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 36613350 6 15 theme linked 836:841 arg1 g 879:879 0.9 g/100 g 869:879 0.9 g/100 g 869:879 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 15 theme linked 836:841 arg1 g 895:895 5.8 g/100 g 885:895 5.8 g/100 g 885:895 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 15 theme linked 836:841 arg1 structures 857:866 glycosidically linked and condensed structures 821:866 glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g) 821:896 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 16 from structures 857:866 arg1 present 810:816 present 810:816 present 810:816 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 16 from structures 857:866 arg1 compounds 764:772 The phenolic compounds 751:772 The phenolic compounds constituent of the HMWM 751:796 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 17 dep = 940:940 arg1 mg/mL 947:951 0.28 mg/mL 942:951 0.28 mg/mL 942:951 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 2 18 theme weight 316:321 arg1 compounds 338:346 high-molecular weight nitrogen-brown compounds 301:346 high-molecular weight nitrogen-brown compounds 301:346 Like coffee grounds processing, chicory roots suffer a roasting process, which may lead to the formation of high-molecular weight nitrogen-brown compounds, the melanoidins. 36613350 2 18 theme weight 316:321 arg1 melanoidins 353:363 the melanoidins 349:363 the melanoidins 349:363 Like coffee grounds processing, chicory roots suffer a roasting process, which may lead to the formation of high-molecular weight nitrogen-brown compounds, the melanoidins. 36613350 7 19 theme Gram-positive 1057:1069 arg1 bacteria 1071:1078 Gram-positive bacteria 1057:1078 Gram-positive bacteria 1057:1078 Chicory HMWM revealed to be effective against Gram-positive bacteria, mainly Staphylococcus aureus and Bacillus cereus, although not so efficient as coffee. 36613350 9 20 theme protective 1498:1507 arg1 effects 1509:1515 the protective effects 1494:1515 the protective effects against pathogenic bacteria 1494:1543 Thus, chicory melanoidins, when used as a food ingredient, may contribute to an antioxidant diet and to prevent diabetes, while increasing the protective effects against pathogenic bacteria. 36613350 6 21 theme reducing 969:976 arg1 capacity 978:985 ferric ion reducing capacity 958:985 ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg) 958:1008 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 21 theme reducing 969:976 arg1 eq/mg 1003:1007 11 µg Fe2+ eq/mg 992:1007 11 µg Fe2+ eq/mg 992:1007 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 22 located present 810:816 arg1 g 879:879 0.9 g/100 g 869:879 0.9 g/100 g 869:879 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 22 located present 810:816 arg1 g 895:895 5.8 g/100 g 885:895 5.8 g/100 g 885:895 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 22 located present 810:816 arg1 structures 857:866 glycosidically linked and condensed structures 821:866 glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g) 821:896 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 22 located present 810:816 arg2 compounds 764:772 The phenolic compounds 751:772 The phenolic compounds constituent of the HMWM 751:796 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 22 located present 810:816 arg2 present 810:816 present 810:816 present 810:816 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 3 23 theme health 436:441 arg1 potential 453:461 health promoting potential 436:461 health promoting potential 436:461 It is hypothesized that similarly to coffee, chicory melanoidins have health promoting potential. 36613350 6 24 dep structures 857:866 arg1 g 879:879 0.9 g/100 g 869:879 0.9 g/100 g 869:879 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 24 dep structures 857:866 arg1 structures 857:866 glycosidically linked and condensed structures 821:866 glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g) 821:896 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 24 dep structures 857:866 arg1 g 895:895 5.8 g/100 g 885:895 5.8 g/100 g 885:895 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 4 25 theme chemical 482:489 arg1 composition 491:501 chemical composition 482:501 chemical composition 482:501 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 9 26 theme food 1397:1400 arg1 ingredient 1402:1411 a food ingredient 1395:1411 a food ingredient 1395:1411 Thus, chicory melanoidins, when used as a food ingredient, may contribute to an antioxidant diet and to prevent diabetes, while increasing the protective effects against pathogenic bacteria. 36613350 8 27 theme type 1319:1322 arg1 mellitus 1335:1342 type 2 diabetes mellitus 1319:1342 type 2 diabetes mellitus treatment 1319:1352 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 3 28 theme promoting 443:451 arg1 potential 453:461 health promoting potential 436:461 health promoting potential 436:461 It is hypothesized that similarly to coffee, chicory melanoidins have health promoting potential. 36613350 5 29 from coffee 743:748 arg1 distinct 729:736 distinct 729:736 distinct 729:736 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 6 30 dep compounds 764:772 arg1 constituent 774:784 constituent 774:784 The phenolic compounds constituent of the HMWM 751:796 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 2 31 theme high-molecular 301:314 arg1 compounds 338:346 high-molecular weight nitrogen-brown compounds 301:346 high-molecular weight nitrogen-brown compounds 301:346 Like coffee grounds processing, chicory roots suffer a roasting process, which may lead to the formation of high-molecular weight nitrogen-brown compounds, the melanoidins. 36613350 2 31 theme high-molecular 301:314 arg1 melanoidins 353:363 the melanoidins 349:363 the melanoidins 349:363 Like coffee grounds processing, chicory roots suffer a roasting process, which may lead to the formation of high-molecular weight nitrogen-brown compounds, the melanoidins. 36613350 6 32 theme ferric 958:963 arg1 capacity 978:985 ferric ion reducing capacity 958:985 ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg) 958:1008 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 32 theme ferric 958:963 arg1 eq/mg 1003:1007 11 µg Fe2+ eq/mg 992:1007 11 µg Fe2+ eq/mg 992:1007 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 33 attach present 810:816 arg1 g 879:879 0.9 g/100 g 869:879 0.9 g/100 g 869:879 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 33 attach present 810:816 arg1 g 895:895 5.8 g/100 g 885:895 5.8 g/100 g 885:895 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 33 attach present 810:816 arg1 structures 857:866 glycosidically linked and condensed structures 821:866 glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g) 821:896 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 33 attach present 810:816 arg2 compounds 764:772 The phenolic compounds 751:772 The phenolic compounds constituent of the HMWM 751:796 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 33 attach present 810:816 arg2 present 810:816 present 810:816 present 810:816 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 0 34 theme Bioactive 0:8 arg1 Properties 10:19 Bioactive Properties 0:19 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 0:108 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 36613350 4 35 theme material 560:567 arg1 composition 491:501 chemical composition 482:501 chemical composition 482:501 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 4 35 theme material 560:567 arg1 activity 518:525 biological activity 507:525 biological activity 507:525 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 6 36 theme phenolic 755:762 arg1 present 810:816 present 810:816 present 810:816 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 36 theme phenolic 755:762 arg1 compounds 764:772 The phenolic compounds 751:772 The phenolic compounds constituent of the HMWM 751:796 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 7 37 dep Bacillus 1114:1121 arg1 cereus 1123:1128 cereus 1123:1128 cereus 1123:1128 Chicory HMWM revealed to be effective against Gram-positive bacteria, mainly Staphylococcus aureus and Bacillus cereus, although not so efficient as coffee. 36613350 0 38 theme Instant 24:30 arg1 Melanoidins 40:50 Instant Chicory Melanoidins 24:50 Instant Chicory Melanoidins 24:50 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 36613350 4 39 theme weight 553:558 arg1 material 560:567 chicory high molecular weight material 530:567 chicory high molecular weight material (HMWM) 530:574 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 4 39 theme weight 553:558 arg1 HMWM 570:573 HMWM 570:573 HMWM 570:573 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 7 40 dep Staphylococcus 1088:1101 arg1 aureus 1103:1108 aureus 1103:1108 aureus 1103:1108 Chicory HMWM revealed to be effective against Gram-positive bacteria, mainly Staphylococcus aureus and Bacillus cereus, although not so efficient as coffee. 36613350 8 41 theme coffee 1260:1265 arg1 HMWM 1267:1270 coffee HMWM 1260:1270 coffee HMWM 1260:1270 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 6 42 theme µg 995:996 arg1 capacity 978:985 ferric ion reducing capacity 958:985 ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg) 958:1008 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 42 theme µg 995:996 arg1 eq/mg 1003:1007 11 µg Fe2+ eq/mg 992:1007 11 µg Fe2+ eq/mg 992:1007 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 1 43 theme Instant 110:116 arg1 worldwide 150:158 a caffeine-free brew worldwide 129:158 a caffeine-free brew worldwide consumed as a coffee substitute 129:190 Instant chicory is a caffeine-free brew worldwide consumed as a coffee substitute. 36613350 1 43 theme Instant 110:116 arg1 chicory 118:124 Instant chicory 110:124 Instant chicory 110:124 Instant chicory is a caffeine-free brew worldwide consumed as a coffee substitute. 36613350 8 44 theme inhibition 1235:1244 arg1 inhibition 1235:1244 inhibition 1235:1244 inhibition 1235:1244 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 8 44 theme inhibition 1235:1244 arg1 % 1230:1230 15% 1228:1230 15% of inhibition 1228:1244 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 9 45 theme chicory 1361:1367 arg1 melanoidins 1369:1379 chicory melanoidins 1361:1379 chicory melanoidins 1361:1379 Thus, chicory melanoidins, when used as a food ingredient, may contribute to an antioxidant diet and to prevent diabetes, while increasing the protective effects against pathogenic bacteria. 36613350 0 46 theme Melanoidins 40:50 arg1 Properties 10:19 Bioactive Properties 0:19 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 0:108 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 36613350 9 47 theme pathogenic 1525:1534 arg1 bacteria 1536:1543 pathogenic bacteria 1525:1543 pathogenic bacteria 1525:1543 Thus, chicory melanoidins, when used as a food ingredient, may contribute to an antioxidant diet and to prevent diabetes, while increasing the protective effects against pathogenic bacteria. 36613350 8 48 theme diabetes 1326:1333 arg1 mellitus 1335:1342 type 2 diabetes mellitus 1319:1342 type 2 diabetes mellitus treatment 1319:1352 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 6 49 link linked 836:841 arg1 g 879:879 0.9 g/100 g 869:879 0.9 g/100 g 869:879 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 49 link linked 836:841 arg1 g 895:895 5.8 g/100 g 885:895 5.8 g/100 g 885:895 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 49 link linked 836:841 arg1 structures 857:866 glycosidically linked and condensed structures 821:866 glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g) 821:896 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 0 50 theme Chicory 32:38 arg1 Melanoidins 40:50 Instant Chicory Melanoidins 24:50 Instant Chicory Melanoidins 24:50 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 36613350 4 51 theme chicory 530:536 arg1 material 560:567 chicory high molecular weight material 530:567 chicory high molecular weight material (HMWM) 530:574 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 4 51 theme chicory 530:536 arg1 HMWM 570:573 HMWM 570:573 HMWM 570:573 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 3 52 theme chicory 411:417 arg1 melanoidins 419:429 chicory melanoidins 411:429 chicory melanoidins 411:429 It is hypothesized that similarly to coffee, chicory melanoidins have health promoting potential. 36613350 6 53 theme HMWM 793:796 arg1 constituent 774:784 constituent 774:784 The phenolic compounds constituent of the HMWM 751:796 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 8 54 theme higher 1248:1253 arg1 activity 1218:1225 α-glucosidase activity 1204:1225 α-glucosidase activity (15% of inhibition) 1204:1245 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 4 55 dep composition 491:501 arg1 the 478:480 the 478:480 the 478:480 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 5 56 theme carbohydrates 638:650 arg1 % 709:709 5.7% 706:709 5.7% (w/w) of protein 706:726 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 56 theme carbohydrates 638:650 arg1 carbohydrates 638:650 carbohydrates 638:650 carbohydrates 638:650 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 56 theme carbohydrates 638:650 arg1 % 627:627 28.9% 623:627 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) 623:700 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 56 theme carbohydrates 638:650 arg1 w/w 712:714 w/w 712:714 w/w 712:714 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 56 theme carbohydrates 638:650 arg1 w/w 630:632 w/w 630:632 w/w 630:632 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 56 theme carbohydrates 638:650 arg1 protein 720:726 protein 720:726 protein 720:726 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 56 theme carbohydrates 638:650 arg1 polysaccharides 674:688 fructose-rich polysaccharides 660:688 fructose-rich polysaccharides (18.7% w/w) 660:700 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 7 57 theme Bacillus 1114:1121 arg1 bacteria 1071:1078 Gram-positive bacteria 1057:1078 Gram-positive bacteria 1057:1078 Chicory HMWM revealed to be effective against Gram-positive bacteria, mainly Staphylococcus aureus and Bacillus cereus, although not so efficient as coffee. 36613350 2 58 theme chicory 225:231 arg1 roots 233:237 chicory roots 225:237 chicory roots 225:237 Like coffee grounds processing, chicory roots suffer a roasting process, which may lead to the formation of high-molecular weight nitrogen-brown compounds, the melanoidins. 36613350 6 59 dep in 907:908 arg1 vitro 910:914 vitro 910:914 vitro 910:914 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 4 60 theme molecular 543:551 arg1 weight 553:558 high molecular weight 538:558 chicory high molecular weight material (HMWM) 530:574 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 6 61 from present 810:816 arg1 g 879:879 0.9 g/100 g 869:879 0.9 g/100 g 869:879 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 61 from present 810:816 arg1 g 895:895 5.8 g/100 g 885:895 5.8 g/100 g 885:895 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 61 from present 810:816 arg1 structures 857:866 glycosidically linked and condensed structures 821:866 glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g) 821:896 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 3 62 contain have 431:434 arg1 melanoidins 419:429 chicory melanoidins 411:429 chicory melanoidins 411:429 It is hypothesized that similarly to coffee, chicory melanoidins have health promoting potential. 36613350 3 62 contain have 431:434 arg2 potential 453:461 health promoting potential 436:461 health promoting potential 436:461 It is hypothesized that similarly to coffee, chicory melanoidins have health promoting potential. 36613350 1 63 dep coffee 174:179 arg1 substitute 181:190 substitute 181:190 substitute 181:190 Instant chicory is a caffeine-free brew worldwide consumed as a coffee substitute. 36613350 2 64 theme compounds 338:346 arg1 formation 288:296 the formation 284:296 the formation of high-molecular weight nitrogen-brown compounds, the melanoidins 284:363 Like coffee grounds processing, chicory roots suffer a roasting process, which may lead to the formation of high-molecular weight nitrogen-brown compounds, the melanoidins. 36613350 4 65 theme high 538:541 arg1 weight 553:558 high molecular weight 538:558 chicory high molecular weight material (HMWM) 530:574 In this work, the chemical composition and biological activity of chicory high molecular weight material (HMWM) was evaluated. 36613350 8 66 used used 1311:1314 arg2 activity 1294:1301 acarbose activity 1285:1301 acarbose activity that is used in type 2 diabetes mellitus treatment 1285:1352 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 2 67 theme grounds 205:211 arg1 processing 213:222 coffee grounds processing 198:222 coffee grounds processing 198:222 Like coffee grounds processing, chicory roots suffer a roasting process, which may lead to the formation of high-molecular weight nitrogen-brown compounds, the melanoidins. 36613350 7 68 theme Chicory 1011:1017 arg1 HMWM 1019:1022 Chicory HMWM 1011:1022 Chicory HMWM 1011:1022 Chicory HMWM revealed to be effective against Gram-positive bacteria, mainly Staphylococcus aureus and Bacillus cereus, although not so efficient as coffee. 36613350 2 69 theme nitrogen-brown 323:336 arg1 compounds 338:346 high-molecular weight nitrogen-brown compounds 301:346 high-molecular weight nitrogen-brown compounds 301:346 Like coffee grounds processing, chicory roots suffer a roasting process, which may lead to the formation of high-molecular weight nitrogen-brown compounds, the melanoidins. 36613350 2 69 theme nitrogen-brown 323:336 arg1 melanoidins 353:363 the melanoidins 349:363 the melanoidins 349:363 Like coffee grounds processing, chicory roots suffer a roasting process, which may lead to the formation of high-molecular weight nitrogen-brown compounds, the melanoidins. 36613350 5 70 theme fructose-rich 660:672 arg1 carbohydrates 638:650 carbohydrates 638:650 carbohydrates 638:650 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 70 theme fructose-rich 660:672 arg1 polysaccharides 674:688 fructose-rich polysaccharides 660:688 fructose-rich polysaccharides (18.7% w/w) 660:700 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 70 theme fructose-rich 660:672 arg1 % 695:695 18.7% w/w 691:699 18.7% w/w 691:699 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 8 71 theme mellitus 1335:1342 arg1 treatment 1344:1352 type 2 diabetes mellitus treatment 1319:1352 type 2 diabetes mellitus treatment 1319:1352 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 8 72 theme acarbose 1285:1292 arg1 activity 1294:1301 acarbose activity 1285:1301 acarbose activity that is used in type 2 diabetes mellitus treatment 1285:1352 It also showed potential to inhibit α-glucosidase activity (15% of inhibition), higher than coffee HMWM, approaching acarbose activity that is used in type 2 diabetes mellitus treatment. 36613350 1 73 theme caffeine-free 131:143 arg1 worldwide 150:158 a caffeine-free brew worldwide 129:158 a caffeine-free brew worldwide consumed as a coffee substitute 129:190 Instant chicory is a caffeine-free brew worldwide consumed as a coffee substitute. 36613350 1 73 theme caffeine-free 131:143 arg1 chicory 118:124 Instant chicory 110:124 Instant chicory 110:124 Instant chicory is a caffeine-free brew worldwide consumed as a coffee substitute. 36613350 6 74 theme Fe2+ 998:1001 arg1 capacity 978:985 ferric ion reducing capacity 958:985 ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg) 958:1008 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 74 theme Fe2+ 998:1001 arg1 eq/mg 1003:1007 11 µg Fe2+ eq/mg 992:1007 11 µg Fe2+ eq/mg 992:1007 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 75 theme = 940:940 arg1 IC50 935:938 IC50 935:938 IC50 = 0.28 mg/mL 935:951 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 2 76 theme roasting 248:255 arg1 process 257:263 a roasting process 246:263 a roasting process 246:263 Like coffee grounds processing, chicory roots suffer a roasting process, which may lead to the formation of high-molecular weight nitrogen-brown compounds, the melanoidins. 36613350 1 77 theme brew 145:148 arg1 worldwide 150:158 a caffeine-free brew worldwide 129:158 a caffeine-free brew worldwide consumed as a coffee substitute 129:190 Instant chicory is a caffeine-free brew worldwide consumed as a coffee substitute. 36613350 1 77 theme brew 145:148 arg1 chicory 118:124 Instant chicory 110:124 Instant chicory 110:124 Instant chicory is a caffeine-free brew worldwide consumed as a coffee substitute. 36613350 6 78 theme ion 965:967 arg1 capacity 978:985 ferric ion reducing capacity 958:985 ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg) 958:1008 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 6 78 theme ion 965:967 arg1 eq/mg 1003:1007 11 µg Fe2+ eq/mg 992:1007 11 µg Fe2+ eq/mg 992:1007 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36613350 0 79 theme Relevance 62:70 arg1 Properties 10:19 Bioactive Properties 0:19 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 0:108 Bioactive Properties of Instant Chicory Melanoidins and Their Relevance as Health Promoting Food Ingredients. 36613350 5 80 theme protein 720:726 arg1 % 709:709 5.7% 706:709 5.7% (w/w) of protein 706:726 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 80 theme protein 720:726 arg1 carbohydrates 638:650 carbohydrates 638:650 carbohydrates 638:650 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 80 theme protein 720:726 arg1 % 627:627 28.9% 623:627 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) 623:700 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 80 theme protein 720:726 arg1 w/w 712:714 w/w 712:714 w/w 712:714 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 80 theme protein 720:726 arg1 w/w 630:632 w/w 630:632 w/w 630:632 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 80 theme protein 720:726 arg1 protein 720:726 protein 720:726 protein 720:726 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 5 80 theme protein 720:726 arg1 polysaccharides 674:688 fructose-rich polysaccharides 660:688 fructose-rich polysaccharides (18.7% w/w) 660:700 The chicory HMWM is composed by 28.9% (w/w) of carbohydrates, mainly fructose-rich polysaccharides (18.7% w/w) and 5.7% (w/w) of protein, distinct from coffee. 36613350 6 81 theme ABTS•+ 916:921 arg1 scavenging 923:932 in vitro ABTS•+ scavenging 907:932 in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) 907:952 The phenolic compounds constituent of the HMWM were mainly present in glycosidically linked and condensed structures (0.9 g/100 g and 5.8 g/100 g), showing in vitro ABTS•+ scavenging (IC50 = 0.28 mg/mL) and ferric ion reducing capacity (ca. 11 µg Fe2+ eq/mg). 36567331 1 0 theme products 180:187 arg1 manufacture 155:165 the manufacture 151:165 the manufacture of bio-based products and bioenergy 151:201 BACKGROUND Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. 36567331 10 1 theme bioproducts 1780:1790 arg1 production 1757:1766 the production 1753:1766 the production of advanced bioproducts 1753:1790 CONCLUSION Our data show that low-recalcitrant poplar biomass obtained with the QsuB technology has the potential to improve the production of advanced bioproducts. 36567331 5 2 theme poplar 720:725 arg1 trees 727:731 poplar trees 720:731 poplar trees 720:731 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 7 3 theme biomass 1037:1043 arg1 deconstruction 1045:1058 downstream biomass deconstruction 1026:1058 downstream biomass deconstruction 1026:1058 RESULTS The impact of these modifications on downstream biomass deconstruction and conversion into advanced bioproducts was evaluated in the current study. 36567331 9 4 theme hydrolysates 1364:1375 arg1 Fermentation 1334:1345 Fermentation 1334:1345 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols 1334:1486 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 2 5 from scale 350:354 arg1 deployment 306:315 the deployment 302:315 the deployment of advanced bioproducts at large scale 302:354 However, the inherent recalcitrance of biomass to conversion into simple sugars currently hinders the deployment of advanced bioproducts at large scale. 36567331 7 6 dep RESULTS 981:987 arg1 evaluated 1105:1113 evaluated 1105:1113 was evaluated in the current study 1101:1134 RESULTS The impact of these modifications on downstream biomass deconstruction and conversion into advanced bioproducts was evaluated in the current study. 36567331 2 7 theme advanced 320:327 arg1 bioproducts 329:339 advanced bioproducts 320:339 advanced bioproducts 320:339 However, the inherent recalcitrance of biomass to conversion into simple sugars currently hinders the deployment of advanced bioproducts at large scale. 36567331 2 8 theme bioproducts 329:339 arg1 deployment 306:315 the deployment 302:315 the deployment of advanced bioproducts at large scale 302:354 However, the inherent recalcitrance of biomass to conversion into simple sugars currently hinders the deployment of advanced bioproducts at large scale. 36567331 9 9 theme bioproducts 1558:1568 arg1 titers 1548:1553 higher titers 1541:1553 higher titers of bioproducts (as much as + 58%) 1541:1587 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 3 10 theme biomass 392:398 arg1 recalcitrance 400:412 biomass recalcitrance 392:412 biomass recalcitrance 392:412 Lignin is a primary contributor to biomass recalcitrance as it protects cell wall polysaccharides from degradation and can inhibit hydrolytic enzymes via non-productive adsorption. 36567331 9 11 from impact 1507:1512 arg1 growth 1522:1527 cell growth 1517:1527 cell growth 1517:1527 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 5 12 theme bacterial 669:677 arg1 QsuB 711:714 QsuB 711:714 QsuB 711:714 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 5 12 theme bacterial 669:677 arg1 dehydratase 698:708 bacterial 3-dehydroshikimate dehydratase 669:708 bacterial 3-dehydroshikimate dehydratase (QsuB) 669:715 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 5 13 from expression 655:664 arg1 trees 727:731 poplar trees 720:731 poplar trees 720:731 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 3 14 theme primary 369:375 arg1 contributor 377:387 a primary contributor 367:387 a primary contributor to biomass recalcitrance 367:412 Lignin is a primary contributor to biomass recalcitrance as it protects cell wall polysaccharides from degradation and can inhibit hydrolytic enzymes via non-productive adsorption. 36567331 3 14 theme primary 369:375 arg1 Lignin 357:362 Lignin 357:362 Lignin 357:362 Lignin is a primary contributor to biomass recalcitrance as it protects cell wall polysaccharides from degradation and can inhibit hydrolytic enzymes via non-productive adsorption. 36567331 5 15 theme dehydratase 698:708 arg1 expression 655:664 expression 655:664 expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees 655:731 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 5 16 theme 3-dehydroshikimate 679:696 arg1 QsuB 711:714 QsuB 711:714 QsuB 711:714 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 5 16 theme 3-dehydroshikimate 679:696 arg1 dehydratase 698:708 bacterial 3-dehydroshikimate dehydratase 669:708 bacterial 3-dehydroshikimate dehydratase (QsuB) 669:715 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 10 17 theme low-recalcitrant 1658:1673 arg1 biomass 1682:1688 low-recalcitrant poplar biomass 1658:1688 low-recalcitrant poplar biomass obtained with the QsuB technology 1658:1722 CONCLUSION Our data show that low-recalcitrant poplar biomass obtained with the QsuB technology has the potential to improve the production of advanced bioproducts. 36567331 10 18 theme advanced 1771:1778 arg1 bioproducts 1780:1790 advanced bioproducts 1771:1790 advanced bioproducts 1771:1790 CONCLUSION Our data show that low-recalcitrant poplar biomass obtained with the QsuB technology has the potential to improve the production of advanced bioproducts. 36567331 1 19 theme bioenergy 193:201 arg1 manufacture 155:165 the manufacture 151:165 the manufacture of bio-based products and bioenergy 151:201 BACKGROUND Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. 36567331 4 20 theme engineering 546:556 arg1 strategies 558:567 Several engineering strategies 538:567 Several engineering strategies 538:567 Several engineering strategies have been designed to reduce lignin or modify its monomeric composition. 36567331 1 21 theme BACKGROUND 85:94 arg1 resources 112:120 BACKGROUND Lignocellulosic resources 85:120 BACKGROUND Lignocellulosic resources 85:120 BACKGROUND Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. 36567331 1 21 theme BACKGROUND 85:94 arg1 feedstocks 136:145 promising feedstocks 126:145 promising feedstocks for the manufacture of bio-based products and bioenergy 126:201 BACKGROUND Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. 36567331 5 22 theme flux 799:802 arg1 redirection 774:784 redirection 774:784 redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin 774:856 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 8 23 theme control 1294:1300 arg1 trees 1302:1306 wild-type control trees 1284:1306 wild-type control trees 1284:1306 Using ionic liquid pretreatment followed by enzymatic saccharification, biomass from engineered trees released more glucose and xylose compared to wild-type control trees under optimum conditions. 36567331 4 24 theme Several 538:544 arg1 strategies 558:567 Several engineering strategies 538:567 Several engineering strategies 538:567 Several engineering strategies have been designed to reduce lignin or modify its monomeric composition. 36567331 7 25 theme modifications 1009:1021 arg1 impact 993:998 The impact 989:998 The impact of these modifications on downstream biomass deconstruction and conversion into advanced bioproducts 989:1099 RESULTS The impact of these modifications on downstream biomass deconstruction and conversion into advanced bioproducts was evaluated in the current study. 36567331 1 26 theme Lignocellulosic 96:110 arg1 resources 112:120 BACKGROUND Lignocellulosic resources 85:120 BACKGROUND Lignocellulosic resources 85:120 BACKGROUND Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. 36567331 1 26 theme Lignocellulosic 96:110 arg1 feedstocks 136:145 promising feedstocks 126:145 promising feedstocks for the manufacture of bio-based products and bioenergy 126:201 BACKGROUND Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. 36567331 8 27 theme wild-type 1284:1292 arg1 trees 1302:1306 wild-type control trees 1284:1306 wild-type control trees 1284:1306 Using ionic liquid pretreatment followed by enzymatic saccharification, biomass from engineered trees released more glucose and xylose compared to wild-type control trees under optimum conditions. 36567331 9 28 theme fatty 1473:1477 arg1 alcohols 1479:1486 fatty alcohols 1473:1486 fatty alcohols 1473:1486 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 8 29 theme liquid 1149:1154 arg1 pretreatment 1156:1167 ionic liquid pretreatment 1143:1167 ionic liquid pretreatment followed by enzymatic saccharification 1143:1206 Using ionic liquid pretreatment followed by enzymatic saccharification, biomass from engineered trees released more glucose and xylose compared to wild-type control trees under optimum conditions. 36567331 2 30 theme large 344:348 arg1 scale 350:354 large scale 344:354 large scale 344:354 However, the inherent recalcitrance of biomass to conversion into simple sugars currently hinders the deployment of advanced bioproducts at large scale. 36567331 9 31 theme higher 1541:1546 arg1 titers 1548:1553 higher titers 1541:1553 higher titers of bioproducts (as much as + 58%) 1541:1587 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 0 32 theme low-lignin 25:34 arg1 poplar 36:41 engineered low-lignin poplar 14:41 engineered low-lignin poplar 14:41 Evaluation of engineered low-lignin poplar for conversion into advanced bioproducts. 36567331 7 33 theme downstream 1026:1035 arg1 deconstruction 1045:1058 downstream biomass deconstruction 1026:1058 downstream biomass deconstruction 1026:1058 RESULTS The impact of these modifications on downstream biomass deconstruction and conversion into advanced bioproducts was evaluated in the current study. 36567331 8 34 theme ionic 1143:1147 arg1 pretreatment 1156:1167 ionic liquid pretreatment 1143:1167 ionic liquid pretreatment followed by enzymatic saccharification 1143:1206 Using ionic liquid pretreatment followed by enzymatic saccharification, biomass from engineered trees released more glucose and xylose compared to wild-type control trees under optimum conditions. 36567331 10 35 dep CONCLUSION 1628:1637 arg1 show 1648:1651 show 1648:1651 show that low-recalcitrant poplar biomass obtained with the QsuB technology has the potential to improve the production of advanced bioproducts 1648:1790 CONCLUSION Our data show that low-recalcitrant poplar biomass obtained with the QsuB technology has the potential to improve the production of advanced bioproducts. 36567331 0 36 theme engineered 14:23 arg1 poplar 36:41 engineered low-lignin poplar 14:41 engineered low-lignin poplar 14:41 Evaluation of engineered low-lignin poplar for conversion into advanced bioproducts. 36567331 9 37 theme toruloides 1398:1407 arg1 strains 1409:1415 Rhodosporidium toruloides strains 1383:1415 Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols 1383:1486 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 6 38 theme compounds 939:947 arg1 pools 921:925 the pools 917:925 the pools of aromatic compounds that accumulate in the biomass 917:978 This reduction was accompanied with remarkable changes in the pools of aromatic compounds that accumulate in the biomass. 36567331 1 39 theme promising 126:134 arg1 resources 112:120 BACKGROUND Lignocellulosic resources 85:120 BACKGROUND Lignocellulosic resources 85:120 BACKGROUND Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. 36567331 1 39 theme promising 126:134 arg1 feedstocks 136:145 promising feedstocks 126:145 promising feedstocks for the manufacture of bio-based products and bioenergy 126:201 BACKGROUND Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. 36567331 3 40 theme non-productive 511:524 arg1 adsorption 526:535 non-productive adsorption 511:535 non-productive adsorption 511:535 Lignin is a primary contributor to biomass recalcitrance as it protects cell wall polysaccharides from degradation and can inhibit hydrolytic enzymes via non-productive adsorption. 36567331 6 41 from changes 906:912 arg1 pools 921:925 the pools 917:925 the pools of aromatic compounds that accumulate in the biomass 917:978 This reduction was accompanied with remarkable changes in the pools of aromatic compounds that accumulate in the biomass. 36567331 4 42 theme monomeric 619:627 arg1 composition 629:639 its monomeric composition 615:639 its monomeric composition 615:639 Several engineering strategies have been designed to reduce lignin or modify its monomeric composition. 36567331 6 43 theme aromatic 930:937 arg1 compounds 939:947 aromatic compounds 930:947 aromatic compounds that accumulate in the biomass 930:978 This reduction was accompanied with remarkable changes in the pools of aromatic compounds that accumulate in the biomass. 36567331 3 44 theme hydrolytic 488:497 arg1 enzymes 499:505 hydrolytic enzymes 488:505 hydrolytic enzymes 488:505 Lignin is a primary contributor to biomass recalcitrance as it protects cell wall polysaccharides from degradation and can inhibit hydrolytic enzymes via non-productive adsorption. 36567331 0 45 theme poplar 36:41 arg1 Evaluation 0:9 Evaluation 0:9 Evaluation of engineered low-lignin poplar for conversion into advanced bioproducts. 0:83 Evaluation of engineered low-lignin poplar for conversion into advanced bioproducts. 36567331 9 46 theme negative 1498:1505 arg1 impact 1507:1512 no negative impact 1495:1512 no negative impact on cell growth 1495:1527 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 5 47 theme lignin 851:856 arg1 expense 840:846 the expense 836:846 the expense of lignin 836:856 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 9 48 theme resulting 1354:1362 arg1 hydrolysates 1364:1375 the resulting hydrolysates 1350:1375 the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols 1350:1486 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 3 49 theme cell 429:432 arg1 polysaccharides 439:453 cell wall polysaccharides 429:453 cell wall polysaccharides 429:453 Lignin is a primary contributor to biomass recalcitrance as it protects cell wall polysaccharides from degradation and can inhibit hydrolytic enzymes via non-productive adsorption. 36567331 8 50 theme optimum 1314:1320 arg1 conditions 1322:1331 optimum conditions 1314:1331 optimum conditions 1314:1331 Using ionic liquid pretreatment followed by enzymatic saccharification, biomass from engineered trees released more glucose and xylose compared to wild-type control trees under optimum conditions. 36567331 8 51 from trees 1233:1237 arg1 biomass 1209:1215 biomass 1209:1215 biomass from engineered trees 1209:1237 Using ionic liquid pretreatment followed by enzymatic saccharification, biomass from engineered trees released more glucose and xylose compared to wild-type control trees under optimum conditions. 36567331 10 52 contain has 1724:1726 arg2 potential 1732:1740 the potential to improve the production of advanced bioproducts 1728:1790 the potential to improve the production of advanced bioproducts 1728:1790 CONCLUSION Our data show that low-recalcitrant poplar biomass obtained with the QsuB technology has the potential to improve the production of advanced bioproducts. 36567331 10 52 contain has 1724:1726 arg1 biomass 1682:1688 low-recalcitrant poplar biomass 1658:1688 low-recalcitrant poplar biomass obtained with the QsuB technology 1658:1722 CONCLUSION Our data show that low-recalcitrant poplar biomass obtained with the QsuB technology has the potential to improve the production of advanced bioproducts. 36567331 7 53 from impact 993:998 arg1 conversion 1064:1073 conversion 1064:1073 conversion into advanced bioproducts 1064:1099 RESULTS The impact of these modifications on downstream biomass deconstruction and conversion into advanced bioproducts was evaluated in the current study. 36567331 7 53 from impact 993:998 arg1 deconstruction 1045:1058 downstream biomass deconstruction 1026:1058 downstream biomass deconstruction 1026:1058 RESULTS The impact of these modifications on downstream biomass deconstruction and conversion into advanced bioproducts was evaluated in the current study. 36567331 3 54 theme wall 434:437 arg1 polysaccharides 439:453 cell wall polysaccharides 429:453 cell wall polysaccharides 429:453 Lignin is a primary contributor to biomass recalcitrance as it protects cell wall polysaccharides from degradation and can inhibit hydrolytic enzymes via non-productive adsorption. 36567331 2 55 theme biomass 243:249 arg1 recalcitrance 226:238 the inherent recalcitrance 213:238 the inherent recalcitrance of biomass to conversion into simple sugars 213:282 However, the inherent recalcitrance of biomass to conversion into simple sugars currently hinders the deployment of advanced bioproducts at large scale. 36567331 9 56 theme QsuB 1604:1607 arg1 trees 1621:1625 QsuB transgenics trees 1604:1625 QsuB transgenics trees 1604:1625 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 9 57 theme cell 1517:1520 arg1 growth 1522:1527 cell growth 1517:1527 cell growth 1517:1527 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 8 58 theme engineered 1222:1231 arg1 trees 1233:1237 engineered trees 1222:1237 engineered trees 1222:1237 Using ionic liquid pretreatment followed by enzymatic saccharification, biomass from engineered trees released more glucose and xylose compared to wild-type control trees under optimum conditions. 36567331 5 59 from expense 840:846 arg1 redirection 774:784 redirection 774:784 redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin 774:856 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 9 60 theme transgenics 1609:1619 arg1 trees 1621:1625 QsuB transgenics trees 1604:1625 QsuB transgenics trees 1604:1625 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 5 61 from reduction 747:755 arg1 lignin 760:765 lignin 760:765 lignin 760:765 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 36567331 7 62 theme current 1122:1128 arg1 study 1130:1134 the current study 1118:1134 the current study 1118:1134 RESULTS The impact of these modifications on downstream biomass deconstruction and conversion into advanced bioproducts was evaluated in the current study. 36567331 2 63 theme inherent 217:224 arg1 recalcitrance 226:238 the inherent recalcitrance 213:238 the inherent recalcitrance of biomass to conversion into simple sugars 213:282 However, the inherent recalcitrance of biomass to conversion into simple sugars currently hinders the deployment of advanced bioproducts at large scale. 36567331 9 64 theme trees 1621:1625 arg1 case 1596:1599 the case 1592:1599 the case of QsuB transgenics trees 1592:1625 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 10 65 theme poplar 1675:1680 arg1 biomass 1682:1688 low-recalcitrant poplar biomass 1658:1688 low-recalcitrant poplar biomass obtained with the QsuB technology 1658:1722 CONCLUSION Our data show that low-recalcitrant poplar biomass obtained with the QsuB technology has the potential to improve the production of advanced bioproducts. 36567331 6 66 theme remarkable 895:904 arg1 changes 906:912 remarkable changes 895:912 remarkable changes in the pools of aromatic compounds that accumulate in the biomass 895:978 This reduction was accompanied with remarkable changes in the pools of aromatic compounds that accumulate in the biomass. 36567331 7 67 theme advanced 1080:1087 arg1 bioproducts 1089:1099 advanced bioproducts 1080:1099 advanced bioproducts 1080:1099 RESULTS The impact of these modifications on downstream biomass deconstruction and conversion into advanced bioproducts was evaluated in the current study. 36567331 9 68 theme Rhodosporidium 1383:1396 arg1 strains 1409:1415 Rhodosporidium toruloides strains 1383:1415 Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols 1383:1486 Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. 36567331 0 69 theme advanced 63:70 arg1 bioproducts 72:82 advanced bioproducts 63:82 advanced bioproducts 63:82 Evaluation of engineered low-lignin poplar for conversion into advanced bioproducts. 36567331 2 70 theme simple 270:275 arg1 sugars 277:282 simple sugars 270:282 simple sugars 270:282 However, the inherent recalcitrance of biomass to conversion into simple sugars currently hinders the deployment of advanced bioproducts at large scale. 36567331 10 71 theme QsuB 1708:1711 arg1 technology 1713:1722 the QsuB technology 1704:1722 the QsuB technology 1704:1722 CONCLUSION Our data show that low-recalcitrant poplar biomass obtained with the QsuB technology has the potential to improve the production of advanced bioproducts. 36567331 1 72 theme bio-based 170:178 arg1 products 180:187 bio-based products 170:187 bio-based products 170:187 BACKGROUND Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. 36567331 8 73 theme enzymatic 1181:1189 arg1 saccharification 1191:1206 enzymatic saccharification 1181:1206 enzymatic saccharification 1181:1206 Using ionic liquid pretreatment followed by enzymatic saccharification, biomass from engineered trees released more glucose and xylose compared to wild-type control trees under optimum conditions. 36567331 5 74 theme metabolic 789:797 arg1 flux 799:802 metabolic flux 789:802 metabolic flux toward 3,4-dihydroxybenzoate 789:831 For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. 35890466 0 0 theme Tree 87:90 arg1 Fruits 114:119 Service Tree (Sorbus domestica L.) Fruits 79:119 Service Tree (Sorbus domestica L.) Fruits 79:119 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 0 0 theme Tree 87:90 arg1 L. 110:111 Sorbus domestica L. 93:111 Sorbus domestica L. 93:111 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 8 1 theme neochlorogenic 943:956 arg1 acids 984:988 quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids 918:988 quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids 918:988 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 8 1 theme neochlorogenic 943:956 arg1 constituents 1014:1025 the major phenolic constituents 995:1025 the major phenolic constituents 995:1025 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 2 2 theme linoleic 330:337 arg1 acid 339:342 linoleic acid 330:342 linoleic acid 330:342 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 6 3 theme acid 604:607 arg1 analysis 621:628 The amino acid composition analysis 594:628 The amino acid composition analysis 594:628 The amino acid composition analysis suggested that the non-essential amino acids predominated over the essential ones. 35890466 0 4 theme Service 79:85 arg1 Fruits 114:119 Service Tree (Sorbus domestica L.) Fruits 79:119 Service Tree (Sorbus domestica L.) Fruits 79:119 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 0 4 theme Service 79:85 arg1 L. 110:111 Sorbus domestica L. 93:111 Sorbus domestica L. 93:111 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 8 5 theme 3,4-dihydroxybenzoic 963:982 arg1 acids 984:988 quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids 918:988 quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids 918:988 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 8 5 theme 3,4-dihydroxybenzoic 963:982 arg1 constituents 1014:1025 the major phenolic constituents 995:1025 the major phenolic constituents 995:1025 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 6 6 theme amino 598:602 arg1 analysis 621:628 The amino acid composition analysis 594:628 The amino acid composition analysis 594:628 The amino acid composition analysis suggested that the non-essential amino acids predominated over the essential ones. 35890466 0 7 theme Sorbus 93:98 arg1 Fruits 114:119 Service Tree (Sorbus domestica L.) Fruits 79:119 Service Tree (Sorbus domestica L.) Fruits 79:119 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 0 7 theme Sorbus 93:98 arg1 L. 110:111 Sorbus domestica L. 93:111 Sorbus domestica L. 93:111 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 5 8 theme ultra-trace 572:582 arg1 Potassium 502:510 Potassium 502:510 Potassium 502:510 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 8 theme ultra-trace 572:582 arg1 iron 513:516 iron 513:516 iron 513:516 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 8 theme ultra-trace 572:582 arg1 boron 523:527 boron 523:527 boron 523:527 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 8 theme ultra-trace 572:582 arg1 elements 584:591 the most abundant macro-, micro-, and ultra-trace elements 534:591 the most abundant macro-, micro-, and ultra-trace elements 534:591 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 7 9 theme polysaccharides 847:861 arg1 part 839:842 the major part 829:842 the major part of polysaccharides 829:861 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 4 10 theme lipophilic 465:474 arg1 pigments 476:483 lipophilic pigments 465:483 lipophilic pigments 465:483 Small amounts of lipophilic pigments were quantified. 35890466 7 11 theme content 802:808 arg1 part 771:774 a large part 763:774 a large part of the total carbohydrate content 763:808 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 7 12 theme major 833:837 arg1 part 839:842 the major part 829:842 the major part of polysaccharides 829:861 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 7 13 theme Soluble 713:719 arg1 sugars 721:726 Soluble sugars 713:726 Soluble sugars (fructose and glucose) 713:749 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 7 13 theme Soluble 713:719 arg1 glucose 742:748 glucose 742:748 glucose 742:748 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 7 13 theme Soluble 713:719 arg1 fructose 729:736 fructose 729:736 fructose 729:736 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 10 14 theme Service 1131:1137 arg1 fruits 1144:1149 Service tree fruits 1131:1149 Service tree fruits 1131:1149 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 9 15 theme peroxyl 1100:1106 arg1 radicals 1121:1128 peroxyl and hydroxyl radicals 1100:1128 radicals 1121:1128 Fruits exhibited free-radical scavenging and protecting ability against peroxyl and hydroxyl radicals. 35890466 2 16 theme palmitic 256:263 arg1 acid 265:268 palmitic acid 256:268 palmitic acid 256:268 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 2 16 theme palmitic 256:263 arg1 acid 318:321 the most commonly occurring saturated fatty acid 274:321 the most commonly occurring saturated fatty acid 274:321 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 2 17 theme major 360:364 arg1 acid 388:391 the major polyunsaturated fatty acid 356:391 the major polyunsaturated fatty acid 356:391 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 2 18 theme fatty 382:386 arg1 acid 388:391 the major polyunsaturated fatty acid 356:391 the major polyunsaturated fatty acid 356:391 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 0 19 theme domestica 100:108 arg1 Fruits 114:119 Service Tree (Sorbus domestica L.) Fruits 79:119 Service Tree (Sorbus domestica L.) Fruits 79:119 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 0 19 theme domestica 100:108 arg1 L. 110:111 Sorbus domestica L. 93:111 Sorbus domestica L. 93:111 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 5 20 theme macro- 552:557 arg1 Potassium 502:510 Potassium 502:510 Potassium 502:510 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 20 theme macro- 552:557 arg1 iron 513:516 iron 513:516 iron 513:516 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 20 theme macro- 552:557 arg1 boron 523:527 boron 523:527 boron 523:527 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 20 theme macro- 552:557 arg1 elements 584:591 the most abundant macro-, micro-, and ultra-trace elements 534:591 the most abundant macro-, micro-, and ultra-trace elements 534:591 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 8 21 theme Malic 864:868 arg1 acid 905:908 the most abundant organic acid 879:908 the most abundant organic acid 879:908 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 8 21 theme Malic 864:868 arg1 acid 870:873 Malic acid 864:873 Malic acid 864:873 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 2 22 theme polyunsaturated 366:380 arg1 acid 388:391 the major polyunsaturated fatty acid 356:391 the major polyunsaturated fatty acid 356:391 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 4 23 theme pigments 476:483 arg1 pigments 476:483 lipophilic pigments 465:483 lipophilic pigments 465:483 Small amounts of lipophilic pigments were quantified. 35890466 4 23 theme pigments 476:483 arg1 amounts 454:460 Small amounts 448:460 Small amounts of lipophilic pigments 448:483 Small amounts of lipophilic pigments were quantified. 35890466 10 24 theme bioactive 1169:1177 arg1 constituents 1179:1190 valuable bioactive constituents 1160:1190 valuable bioactive constituents having a high nutritional value and potential health benefits 1160:1252 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 2 25 theme occurring 292:300 arg1 acid 318:321 the most commonly occurring saturated fatty acid 274:321 the most commonly occurring saturated fatty acid 274:321 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 2 25 theme occurring 292:300 arg1 acid 265:268 palmitic acid 256:268 palmitic acid 256:268 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 9 26 theme hydroxyl 1112:1119 arg1 radicals 1121:1128 peroxyl and hydroxyl radicals 1100:1128 radicals 1121:1128 Fruits exhibited free-radical scavenging and protecting ability against peroxyl and hydroxyl radicals. 35890466 1 27 theme major 163:167 arg1 constituents 191:202 the major and minor nutritional constituents 159:202 the major and minor nutritional constituents of Sorbus domestica L. fruits 159:232 The current study aimed to determine the major and minor nutritional constituents of Sorbus domestica L. fruits. 35890466 0 28 theme Nutrient 0:7 arg1 Constituents 9:20 Nutrient Constituents 0:20 Nutrient Constituents 0:20 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 7 29 theme total 783:787 arg1 content 802:808 the total carbohydrate content 779:808 the total carbohydrate content 779:808 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 5 30 theme micro- 560:565 arg1 Potassium 502:510 Potassium 502:510 Potassium 502:510 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 30 theme micro- 560:565 arg1 iron 513:516 iron 513:516 iron 513:516 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 30 theme micro- 560:565 arg1 boron 523:527 boron 523:527 boron 523:527 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 30 theme micro- 560:565 arg1 elements 584:591 the most abundant macro-, micro-, and ultra-trace elements 534:591 the most abundant macro-, micro-, and ultra-trace elements 534:591 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 0 31 theme Bioactive 23:31 arg1 Phytochemicals 33:46 Bioactive Phytochemicals 23:46 Bioactive Phytochemicals 23:46 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 7 32 theme carbohydrate 789:800 arg1 content 802:808 the total carbohydrate content 779:808 the total carbohydrate content 779:808 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 0 33 theme Fruits 114:119 arg1 Properties 65:74 Antioxidant Properties 53:74 Antioxidant Properties 53:74 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 0 33 theme Fruits 114:119 arg1 Constituents 9:20 Nutrient Constituents 0:20 Nutrient Constituents 0:20 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 0 33 theme Fruits 114:119 arg1 Phytochemicals 33:46 Bioactive Phytochemicals 23:46 Bioactive Phytochemicals 23:46 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 8 34 theme phenolic 1005:1012 arg1 acids 984:988 quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids 918:988 quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids 918:988 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 8 34 theme phenolic 1005:1012 arg1 constituents 1014:1025 the major phenolic constituents 995:1025 the major phenolic constituents 995:1025 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 1 35 theme minor 173:177 arg1 constituents 191:202 the major and minor nutritional constituents 159:202 the major and minor nutritional constituents of Sorbus domestica L. fruits 159:232 The current study aimed to determine the major and minor nutritional constituents of Sorbus domestica L. fruits. 35890466 10 36 contain having 1192:1197 arg2 benefits 1245:1252 potential health benefits 1228:1252 potential health benefits 1228:1252 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 10 36 contain having 1192:1197 arg2 value 1218:1222 a high nutritional value 1199:1222 a high nutritional value 1199:1222 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 10 36 contain having 1192:1197 arg1 constituents 1179:1190 valuable bioactive constituents 1160:1190 valuable bioactive constituents having a high nutritional value and potential health benefits 1160:1252 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 10 37 theme health 1238:1243 arg1 benefits 1245:1252 potential health benefits 1228:1252 potential health benefits 1228:1252 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 10 38 theme tree 1139:1142 arg1 fruits 1144:1149 Service tree fruits 1131:1149 Service tree fruits 1131:1149 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 6 39 theme amino 663:667 arg1 acids 669:673 the non-essential amino acids 645:673 the non-essential amino acids 645:673 The amino acid composition analysis suggested that the non-essential amino acids predominated over the essential ones. 35890466 1 40 theme nutritional 179:189 arg1 constituents 191:202 the major and minor nutritional constituents 159:202 the major and minor nutritional constituents of Sorbus domestica L. fruits 159:232 The current study aimed to determine the major and minor nutritional constituents of Sorbus domestica L. fruits. 35890466 6 41 theme essential 697:705 arg1 ones 707:710 the essential ones 693:710 the essential ones 693:710 The amino acid composition analysis suggested that the non-essential amino acids predominated over the essential ones. 35890466 9 42 theme protecting 1073:1082 arg1 ability 1084:1090 free-radical scavenging and protecting ability 1045:1090 ability 1084:1090 Fruits exhibited free-radical scavenging and protecting ability against peroxyl and hydroxyl radicals. 35890466 6 43 theme non-essential 649:661 arg1 acids 669:673 the non-essential amino acids 645:673 the non-essential amino acids 645:673 The amino acid composition analysis suggested that the non-essential amino acids predominated over the essential ones. 35890466 3 44 theme sterol 398:403 arg1 fraction 405:412 The sterol fraction 394:412 The sterol fraction 394:412 The sterol fraction consisted mainly of β-sitosterol. 35890466 7 45 theme large 765:769 arg1 part 771:774 a large part 763:774 a large part of the total carbohydrate content 763:808 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 10 46 theme valuable 1160:1167 arg1 constituents 1179:1190 valuable bioactive constituents 1160:1190 valuable bioactive constituents having a high nutritional value and potential health benefits 1160:1252 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 8 47 theme organic 897:903 arg1 acid 905:908 the most abundant organic acid 879:908 the most abundant organic acid 879:908 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 8 47 theme organic 897:903 arg1 acid 870:873 Malic acid 864:873 Malic acid 864:873 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 0 48 theme Antioxidant 53:63 arg1 Properties 65:74 Antioxidant Properties 53:74 Antioxidant Properties 53:74 Nutrient Constituents, Bioactive Phytochemicals, and Antioxidant Properties of Service Tree (Sorbus domestica L.) Fruits. 35890466 10 49 theme high 1201:1204 arg1 value 1218:1222 a high nutritional value 1199:1222 a high nutritional value 1199:1222 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 4 50 theme Small 448:452 arg1 pigments 476:483 lipophilic pigments 465:483 lipophilic pigments 465:483 Small amounts of lipophilic pigments were quantified. 35890466 4 50 theme Small 448:452 arg1 amounts 454:460 Small amounts 448:460 Small amounts of lipophilic pigments 448:483 Small amounts of lipophilic pigments were quantified. 35890466 8 51 theme abundant 888:895 arg1 acid 905:908 the most abundant organic acid 879:908 the most abundant organic acid 879:908 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 8 51 theme abundant 888:895 arg1 acid 870:873 Malic acid 864:873 Malic acid 864:873 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 8 52 theme major 999:1003 arg1 acids 984:988 quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids 918:988 quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids 918:988 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 8 52 theme major 999:1003 arg1 constituents 1014:1025 the major phenolic constituents 995:1025 the major phenolic constituents 995:1025 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 5 53 theme abundant 543:550 arg1 Potassium 502:510 Potassium 502:510 Potassium 502:510 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 53 theme abundant 543:550 arg1 iron 513:516 iron 513:516 iron 513:516 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 53 theme abundant 543:550 arg1 boron 523:527 boron 523:527 boron 523:527 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 5 53 theme abundant 543:550 arg1 elements 584:591 the most abundant macro-, micro-, and ultra-trace elements 534:591 the most abundant macro-, micro-, and ultra-trace elements 534:591 Potassium, iron, and boron were the most abundant macro-, micro-, and ultra-trace elements. 35890466 2 54 theme fatty 312:316 arg1 acid 318:321 the most commonly occurring saturated fatty acid 274:321 the most commonly occurring saturated fatty acid 274:321 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 2 54 theme fatty 312:316 arg1 acid 265:268 palmitic acid 256:268 palmitic acid 256:268 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 1 55 theme Sorbus 207:212 arg1 fruits 227:232 Sorbus domestica L. fruits 207:232 Sorbus domestica L. fruits 207:232 The current study aimed to determine the major and minor nutritional constituents of Sorbus domestica L. fruits. 35890466 7 56 dep sugars 721:726 arg1 sugars 721:726 Soluble sugars 713:726 Soluble sugars (fructose and glucose) 713:749 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 7 56 dep sugars 721:726 arg1 glucose 742:748 glucose 742:748 glucose 742:748 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 7 56 dep sugars 721:726 arg1 fructose 729:736 fructose 729:736 fructose 729:736 Soluble sugars (fructose and glucose) represented a large part of the total carbohydrate content, but pectin formed the major part of polysaccharides. 35890466 2 57 theme saturated 302:310 arg1 acid 318:321 the most commonly occurring saturated fatty acid 274:321 the most commonly occurring saturated fatty acid 274:321 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 2 57 theme saturated 302:310 arg1 acid 265:268 palmitic acid 256:268 palmitic acid 256:268 It was revealed that palmitic acid was the most commonly occurring saturated fatty acid, while linoleic acid represented the major polyunsaturated fatty acid. 35890466 1 58 theme domestica 214:222 arg1 fruits 227:232 Sorbus domestica L. fruits 207:232 Sorbus domestica L. fruits 207:232 The current study aimed to determine the major and minor nutritional constituents of Sorbus domestica L. fruits. 35890466 8 59 theme quercetin-3-β-glucoside 918:940 arg1 acids 984:988 quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids 918:988 quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids 918:988 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 8 59 theme quercetin-3-β-glucoside 918:940 arg1 constituents 1014:1025 the major phenolic constituents 995:1025 the major phenolic constituents 995:1025 Malic acid was the most abundant organic acid whereas quercetin-3-β-glucoside, neochlorogenic, and 3,4-dihydroxybenzoic acids were the major phenolic constituents. 35890466 1 60 theme current 126:132 arg1 study 134:138 The current study 122:138 The current study 122:138 The current study aimed to determine the major and minor nutritional constituents of Sorbus domestica L. fruits. 35890466 9 61 theme free-radical 1045:1056 arg1 scavenging 1058:1067 free-radical scavenging and protecting ability 1045:1090 scavenging 1058:1067 Fruits exhibited free-radical scavenging and protecting ability against peroxyl and hydroxyl radicals. 35890466 1 62 theme L. 224:225 arg1 fruits 227:232 Sorbus domestica L. fruits 207:232 Sorbus domestica L. fruits 207:232 The current study aimed to determine the major and minor nutritional constituents of Sorbus domestica L. fruits. 35890466 10 63 theme nutritional 1206:1216 arg1 value 1218:1222 a high nutritional value 1199:1222 a high nutritional value 1199:1222 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 10 64 theme potential 1228:1236 arg1 benefits 1245:1252 potential health benefits 1228:1252 potential health benefits 1228:1252 Service tree fruits provided valuable bioactive constituents having a high nutritional value and potential health benefits. 35890466 6 65 theme composition 609:619 arg1 analysis 621:628 The amino acid composition analysis 594:628 The amino acid composition analysis 594:628 The amino acid composition analysis suggested that the non-essential amino acids predominated over the essential ones. 35890466 1 66 theme fruits 227:232 arg1 constituents 191:202 the major and minor nutritional constituents 159:202 the major and minor nutritional constituents of Sorbus domestica L. fruits 159:232 The current study aimed to determine the major and minor nutritional constituents of Sorbus domestica L. fruits. 35863570 0 0 theme bioreactor 86:95 arg1 waste 106:110 anaerobic membrane bioreactor treating waste 67:110 anaerobic membrane bioreactor treating waste 67:110 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 3 1 theme solid 700:704 arg1 liquor 687:692 mixed liquor 681:692 mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively 681:789 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 3 2 with 1:2 773:775 arg1 relaxation 746:755 a filtration: relaxation 732:755 a filtration: relaxation of 4:1 732:762 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 2 3 theme COD 564:566 arg1 efficiency 579:588 the COD conversion efficiency 560:588 the COD conversion efficiency of 40 % 560:596 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 1 4 theme biomass 244:250 arg1 treatment 252:260 biomass treatment 244:260 biomass treatment 244:260 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 0 5 theme membrane 77:84 arg1 waste 106:110 anaerobic membrane bioreactor treating waste 67:110 anaerobic membrane bioreactor treating waste 67:110 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 4 6 theme layer 984:988 arg1 composition 957:967 the main composition 948:967 the main composition of the foulant layer 948:988 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 3 7 theme 4:1 760:762 arg1 relaxation 746:755 a filtration: relaxation 732:755 a filtration: relaxation of 4:1 732:762 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 0 8 theme waste 106:110 arg1 performance 20:30 Long term operation performance 0:30 Long term operation performance 0:30 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 0 8 theme waste 106:110 arg1 mechanisms 53:62 membrane fouling mechanisms 36:62 membrane fouling mechanisms 36:62 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 1 9 theme critical 360:367 arg1 issues 369:374 critical issues 360:374 critical issues 360:374 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 5 10 theme predominant 1038:1048 arg1 causes 1050:1055 the predominant causes 1034:1055 the predominant causes of inorganic fouling 1034:1076 Furthermore, phosphorus and magnesium were the predominant causes of inorganic fouling. 35863570 5 10 theme predominant 1038:1048 arg1 magnesium 1019:1027 magnesium 1019:1027 magnesium 1019:1027 Furthermore, phosphorus and magnesium were the predominant causes of inorganic fouling. 35863570 5 10 theme predominant 1038:1048 arg1 phosphorus 1004:1013 phosphorus 1004:1013 phosphorus 1004:1013 Furthermore, phosphorus and magnesium were the predominant causes of inorganic fouling. 35863570 4 11 theme foulant 976:982 arg1 layer 984:988 the foulant layer 972:988 the foulant layer 972:988 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 0 12 theme treating 97:104 arg1 waste 106:110 anaerobic membrane bioreactor treating waste 67:110 anaerobic membrane bioreactor treating waste 67:110 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 3 13 theme mixed 681:685 arg1 liquor 687:692 mixed liquor 681:692 mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively 681:789 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 2 14 theme conversion 568:577 arg1 efficiency 579:588 the COD conversion efficiency 560:588 the COD conversion efficiency of 40 % 560:596 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 3 15 from liquor 687:692 arg1 flux 645:648 the average flux 633:648 the average flux 633:648 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 3 15 from liquor 687:692 arg1 L/m2/h 671:676 9.6, 4.5 and 1.2 L/m2/h 654:676 9.6, 4.5 and 1.2 L/m2/h 654:676 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 1 16 theme energy 266:271 arg1 regeneration 273:284 energy regeneration 266:284 energy regeneration 266:284 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 3 17 with 1:1 765:767 arg1 relaxation 746:755 a filtration: relaxation 732:755 a filtration: relaxation of 4:1 732:762 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 2 18 dep sludge 435:440 arg1 WAS 443:445 WAS 443:445 WAS 443:445 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 7 19 theme comprehensive 1241:1253 arg1 analysis 1255:1262 a comprehensive analysis 1239:1262 a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment 1239:1413 This research provided a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment. 35863570 1 20 theme High 172:175 arg1 HSAnMBR 214:220 HSAnMBR 214:220 HSAnMBR 214:220 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 1 20 theme High 172:175 arg1 bioreactor 202:211 High solid anaerobic membrane bioreactor 172:211 High solid anaerobic membrane bioreactor (HSAnMBR) 172:221 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 2 21 theme gCOD/L·d 496:503 arg1 rates 477:481 organic loading rates 461:481 organic loading rates of 3.69-3.72 gCOD/L·d 461:503 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 2 22 theme organic 461:467 arg1 rates 477:481 organic loading rates 461:481 organic loading rates of 3.69-3.72 gCOD/L·d 461:503 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 1 23 theme solid 177:181 arg1 HSAnMBR 214:220 HSAnMBR 214:220 HSAnMBR 214:220 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 1 23 theme solid 177:181 arg1 bioreactor 202:211 High solid anaerobic membrane bioreactor 172:211 High solid anaerobic membrane bioreactor (HSAnMBR) 172:221 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 0 24 theme term 5:8 arg1 performance 20:30 Long term operation performance 0:30 Long term operation performance 0:30 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 2 25 theme loading 469:475 arg1 rates 477:481 organic loading rates 461:481 organic loading rates of 3.69-3.72 gCOD/L·d 461:503 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 6 26 theme cake 1176:1179 arg1 formation 1187:1195 cake layer formation 1176:1195 cake layer formation 1176:1195 The minerals precipitated on the membrane and were embedded into membrane pores, contributing to cake layer formation and pore blocking. 35863570 1 27 theme anaerobic 183:191 arg1 HSAnMBR 214:220 HSAnMBR 214:220 HSAnMBR 214:220 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 1 27 theme anaerobic 183:191 arg1 bioreactor 202:211 High solid anaerobic membrane bioreactor 172:211 High solid anaerobic membrane bioreactor (HSAnMBR) 172:221 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 0 28 theme Long 0:3 arg1 term 5:8 Long term 0:8 Long term operation performance 0:30 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 2 29 theme % 596:596 arg1 efficiency 579:588 the COD conversion efficiency 560:588 the COD conversion efficiency of 40 % 560:596 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 1 30 theme membrane 193:200 arg1 HSAnMBR 214:220 HSAnMBR 214:220 HSAnMBR 214:220 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 1 30 theme membrane 193:200 arg1 bioreactor 202:211 High solid anaerobic membrane bioreactor 172:211 High solid anaerobic membrane bioreactor (HSAnMBR) 172:221 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 2 31 theme sludge 435:440 arg1 treatment 448:456 waste activated sludge (WAS) treatment 419:456 waste activated sludge (WAS) treatment 419:456 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 7 32 theme membrane 1271:1278 arg1 operation 1280:1288 the membrane operation characterization and fouling mechanisms 1267:1328 operation 1280:1288 This research provided a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment. 35863570 0 33 theme high 132:135 arg1 concentration 143:155 high solid concentration 132:155 high solid concentration 132:155 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 6 34 theme membrane 1144:1151 arg1 pores 1153:1157 membrane pores 1144:1157 membrane pores 1144:1157 The minerals precipitated on the membrane and were embedded into membrane pores, contributing to cake layer formation and pore blocking. 35863570 2 35 theme waste 419:423 arg1 sludge 435:440 waste activated sludge 419:440 waste activated sludge (WAS) treatment 419:456 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 0 36 theme operation 10:18 arg1 performance 20:30 Long term operation performance 0:30 Long term operation performance 0:30 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 4 37 theme fouling 836:842 arg1 characteristics 808:822 The distinctive characteristics 792:822 The distinctive characteristics of membrane fouling at high solid condition 792:866 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 4 38 theme high 847:850 arg1 condition 858:866 high solid condition 847:866 high solid condition 847:866 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 7 39 dep operation 1280:1288 arg1 characterization 1290:1305 characterization 1290:1305 characterization 1290:1305 This research provided a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment. 35863570 0 40 theme membrane 36:43 arg1 mechanisms 53:62 membrane fouling mechanisms 36:62 membrane fouling mechanisms 36:62 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 1 41 theme membrane 293:300 arg1 performance 312:322 membrane operation performance 293:322 membrane operation performance 293:322 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 4 42 theme solid 852:856 arg1 condition 858:866 high solid condition 847:866 high solid condition 847:866 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 7 43 theme HSAnMBR 1377:1383 arg1 applications 1385:1396 forward HSAnMBR applications 1369:1396 forward HSAnMBR applications to WAS treatment 1369:1413 This research provided a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment. 35863570 4 44 theme high 915:918 arg1 propensity 928:937 high fouling propensity 915:937 high fouling propensity 915:937 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 1 45 theme operation 302:310 arg1 performance 312:322 membrane operation performance 293:322 membrane operation performance 293:322 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 0 46 theme solid 137:141 arg1 concentration 143:155 high solid concentration 132:155 high solid concentration 132:155 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 7 47 theme HSAnMBR 1333:1339 arg1 mechanisms 1319:1328 fouling mechanisms 1311:1328 fouling mechanisms 1311:1328 This research provided a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment. 35863570 7 47 theme HSAnMBR 1333:1339 arg1 operation 1280:1288 the membrane operation characterization and fouling mechanisms 1267:1328 operation 1280:1288 This research provided a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment. 35863570 7 48 theme mechanisms 1319:1328 arg1 analysis 1255:1262 a comprehensive analysis 1239:1262 a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment 1239:1413 This research provided a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment. 35863570 5 49 theme fouling 1070:1076 arg1 causes 1050:1055 the predominant causes 1034:1055 the predominant causes of inorganic fouling 1034:1076 Furthermore, phosphorus and magnesium were the predominant causes of inorganic fouling. 35863570 5 49 theme fouling 1070:1076 arg1 magnesium 1019:1027 magnesium 1019:1027 magnesium 1019:1027 Furthermore, phosphorus and magnesium were the predominant causes of inorganic fouling. 35863570 5 49 theme fouling 1070:1076 arg1 phosphorus 1004:1013 phosphorus 1004:1013 phosphorus 1004:1013 Furthermore, phosphorus and magnesium were the predominant causes of inorganic fouling. 35863570 0 50 theme high 161:164 arg1 flux 166:169 high flux 161:169 high flux 161:169 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 4 51 from condition 858:866 arg1 characteristics 808:822 The distinctive characteristics 792:822 The distinctive characteristics of membrane fouling at high solid condition 792:866 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 7 52 theme fouling 1311:1317 arg1 mechanisms 1319:1328 fouling mechanisms 1311:1328 fouling mechanisms 1311:1328 This research provided a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment. 35863570 2 53 used utilized 406:413 arg2 HSAnMBR 394:400 a HSAnMBR 392:400 a HSAnMBR 392:400 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 0 54 theme fouling 45:51 arg1 mechanisms 53:62 membrane fouling mechanisms 36:62 membrane fouling mechanisms 36:62 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 4 55 theme distinctive 796:806 arg1 characteristics 808:822 The distinctive characteristics 792:822 The distinctive characteristics of membrane fouling at high solid condition 792:866 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 6 56 theme layer 1181:1185 arg1 formation 1187:1195 cake layer formation 1176:1195 cake layer formation 1176:1195 The minerals precipitated on the membrane and were embedded into membrane pores, contributing to cake layer formation and pore blocking. 35863570 6 57 theme pore 1201:1204 arg1 blocking 1206:1213 pore blocking 1201:1213 pore blocking 1201:1213 The minerals precipitated on the membrane and were embedded into membrane pores, contributing to cake layer formation and pore blocking. 35863570 1 58 theme membrane 328:335 arg1 control 345:351 membrane fouling control 328:351 membrane fouling control 328:351 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 4 59 theme membrane 827:834 arg1 fouling 836:842 membrane fouling 827:842 membrane fouling 827:842 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 4 60 theme main 952:955 arg1 composition 957:967 the main composition 948:967 the main composition of the foulant layer 948:988 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 7 61 theme operation 1280:1288 arg1 analysis 1255:1262 a comprehensive analysis 1239:1262 a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment 1239:1413 This research provided a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment. 35863570 3 62 theme 1:2 773:775 arg1 solid 700:704 solid 700:704 solid 700:704 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 4 63 theme fouling 920:926 arg1 propensity 928:937 high fouling propensity 915:937 high fouling propensity 915:937 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 3 64 theme average 637:643 arg1 flux 645:648 the average flux 633:648 the average flux 633:648 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 3 64 theme average 637:643 arg1 L/m2/h 671:676 9.6, 4.5 and 1.2 L/m2/h 654:676 9.6, 4.5 and 1.2 L/m2/h 654:676 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 7 65 theme WAS 1401:1403 arg1 treatment 1405:1413 WAS treatment 1401:1413 WAS treatment 1401:1413 This research provided a comprehensive analysis of the membrane operation characterization and fouling mechanisms of HSAnMBR, which was expected to push forward HSAnMBR applications to WAS treatment. 35863570 3 66 with g/L 723:725 arg1 relaxation 746:755 a filtration: relaxation 732:755 a filtration: relaxation of 4:1 732:762 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 3 67 theme filtration 734:743 arg1 relaxation 746:755 a filtration: relaxation 732:755 a filtration: relaxation of 4:1 732:762 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 0 68 theme anaerobic 67:75 arg1 waste 106:110 anaerobic membrane bioreactor treating waste 67:110 anaerobic membrane bioreactor treating waste 67:110 Long term operation performance and membrane fouling mechanisms of anaerobic membrane bioreactor treating waste activated sludge at high solid concentration and high flux. 35863570 5 69 theme inorganic 1060:1068 arg1 fouling 1070:1076 inorganic fouling 1060:1076 inorganic fouling 1060:1076 Furthermore, phosphorus and magnesium were the predominant causes of inorganic fouling. 35863570 4 70 contain had 911:913 arg1 proteins 902:909 proteins 902:909 proteins 902:909 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 4 70 contain had 911:913 arg1 polysaccharides 882:896 polysaccharides 882:896 polysaccharides 882:896 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 4 70 contain had 911:913 arg2 propensity 928:937 high fouling propensity 915:937 high fouling propensity 915:937 The distinctive characteristics of membrane fouling at high solid condition were that the polysaccharides and proteins had high fouling propensity and were the main composition of the foulant layer. 35863570 3 71 theme 1:1 765:767 arg1 solid 700:704 solid 700:704 solid 700:704 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 3 72 theme g/L 723:725 arg1 solid 700:704 solid 700:704 solid 700:704 The membrane operated stably when the average flux was 9.6, 4.5 and 1.2 L/m2/h at mixed liquor total solid of 25, 30 and 40 g/L with a filtration: relaxation of 4:1, 1:1 and 1:2, respectively. 35863570 1 73 theme fouling 337:343 arg1 control 345:351 membrane fouling control 328:351 membrane fouling control 328:351 High solid anaerobic membrane bioreactor (HSAnMBR) is widely applied in biomass treatment and energy regeneration, while membrane operation performance and membrane fouling control remain critical issues. 35863570 2 74 theme activated 425:433 arg1 sludge 435:440 waste activated sludge 419:440 waste activated sludge (WAS) treatment 419:456 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35863570 2 75 theme biogas 509:514 arg1 yield 516:520 biogas yield 509:520 biogas yield 509:520 In this study, a HSAnMBR was utilized for waste activated sludge (WAS) treatment at organic loading rates of 3.69-3.72 gCOD/L·d and biogas yield was ranged in 0.38-0.39 L/gVSfed with the COD conversion efficiency of 40 %. 35511237 2 0 theme non-motile 99:108 arg1 strain 153:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain, designated HU1-3T, was isolated from Ulva in China. 35511237 11 1 theme chemotaxonomic 1383:1396 arg1 data 1423:1426 the phylogenetic, chemotaxonomic, biochemical and genomic data 1365:1426 the phylogenetic, chemotaxonomic, biochemical and genomic data 1365:1426 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 4 2 theme % 607:607 arg1 optimum 621:627 optimum 621:627 optimum 621:627 Strain HU1-3T grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %). 35511237 4 2 theme % 607:607 arg1 NaCl 615:618 2-6 % (w/v) NaCl 603:618 2-6 % (w/v) NaCl (optimum, 2-4 %) 603:635 Strain HU1-3T grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %). 35511237 6 3 theme reference 740:748 arg1 CNU004T 782:788 the reference strain Hyunsoonleella jejuensis CNU004T 736:788 the reference strain Hyunsoonleella jejuensis CNU004T 736:788 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 11 4 theme Hyunsoonleella 1534:1547 arg1 sp 1555:1556 the name Hyunsoonleella ulvae sp 1525:1556 the name Hyunsoonleella ulvae sp 1525:1556 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 6 5 theme jejuensis 772:780 arg1 CNU004T 782:788 the reference strain Hyunsoonleella jejuensis CNU004T 736:788 the reference strain Hyunsoonleella jejuensis CNU004T 736:788 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 6 6 theme Hyunsoonleella 757:770 arg1 CNU004T 782:788 the reference strain Hyunsoonleella jejuensis CNU004T 736:788 the reference strain Hyunsoonleella jejuensis CNU004T 736:788 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 9 7 theme unidentified 1053:1064 arg1 aminolipids 1066:1076 two unidentified aminolipids 1049:1076 two unidentified aminolipids 1049:1076 The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids, and three unknown polar lipids. 35511237 4 8 theme 2-6  603:606 arg1 optimum 621:627 optimum 621:627 optimum 621:627 Strain HU1-3T grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %). 35511237 4 8 theme 2-6  603:606 arg1 NaCl 615:618 2-6 % (w/v) NaCl 603:618 2-6 % (w/v) NaCl (optimum, 2-4 %) 603:635 Strain HU1-3T grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %). 35511237 1 9 from algae 45:49 arg1 China 54:58 China 54:58 China 54:58 nov., isolated from algae in China. 35511237 3 10 theme Hyunsoonleella 330:343 arg1 member 310:315 a member 308:315 a member of the genus Hyunsoonleella 308:343 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 2 11 theme aerobic 90:96 arg1 strain 153:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain, designated HU1-3T, was isolated from Ulva in China. 35511237 11 12 dep Hyunsoonleella 1534:1547 arg1 ulvae 1549:1553 ulvae 1549:1553 ulvae 1549:1553 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 10 13 theme polysaccharides 1342:1356 arg1 kinds 1333:1337 various kinds 1325:1337 various kinds of polysaccharides 1325:1356 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 9 14 theme unknown 1089:1095 arg1 lipids 1103:1108 three unknown polar lipids 1083:1108 three unknown polar lipids 1083:1108 The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids, and three unknown polar lipids. 35511237 2 15 theme bacterial 143:151 arg1 strain 153:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain, designated HU1-3T, was isolated from Ulva in China. 35511237 7 16 theme iso 919:921 arg1  0 915:916  0 915:916  0 915:916 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 7 16 theme iso 919:921 arg1 G-C15  923:928 iso G-C15  919:928 iso G-C15  919:928 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 13 17 theme =KCTC 1604:1608 arg1 HU1-3T 1596:1601 HU1-3T 1596:1601 HU1-3T (=KCTC 82511T=MCCC 1K05798T) 1596:1630 The type strain is HU1-3T (=KCTC 82511T=MCCC 1K05798T). 35511237 13 17 theme =KCTC 1604:1608 arg1 1K05798T 1622:1629 =KCTC 82511T=MCCC 1K05798T 1604:1629 =KCTC 82511T=MCCC 1K05798T 1604:1629 The type strain is HU1-3T (=KCTC 82511T=MCCC 1K05798T). 35511237 6 18 theme HU1-3T 839:844 arg1 value 823:827 the average nucleotide identity value 791:827 the average nucleotide identity value of strain HU1-3T 791:844 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 6 18 theme HU1-3T 839:844 arg1 % 855:855 77.9 % 850:855 77.9 % 850:855 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 2 19 theme yellow-pigmented 126:141 arg1 strain 153:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain, designated HU1-3T, was isolated from Ulva in China. 35511237 10 20 theme strain 1252:1257 arg1 HU1-3T 1259:1264 strain HU1-3T 1252:1264 strain HU1-3T 1252:1264 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 13 21 theme 82511T=MCCC 1610:1620 arg1 HU1-3T 1596:1601 HU1-3T 1596:1601 HU1-3T (=KCTC 82511T=MCCC 1K05798T) 1596:1630 The type strain is HU1-3T (=KCTC 82511T=MCCC 1K05798T). 35511237 13 21 theme 82511T=MCCC 1610:1620 arg1 1K05798T 1622:1629 =KCTC 82511T=MCCC 1K05798T 1604:1629 =KCTC 82511T=MCCC 1K05798T 1604:1629 The type strain is HU1-3T (=KCTC 82511T=MCCC 1K05798T). 35511237 2 22 attach isolated 184:191 arg2 strain 153:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain, designated HU1-3T, was isolated from Ulva in China. 35511237 2 22 attach isolated 184:191 arg1 Ulva 198:201 Ulva 198:201 Ulva in China 198:210 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain, designated HU1-3T, was isolated from Ulva in China. 35511237 3 23 theme genus 324:328 arg1 Hyunsoonleella 330:343 the genus Hyunsoonleella 320:343 the genus Hyunsoonleella 320:343 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 11 24 theme strain 1429:1434 arg1 HU1-3T 1436:1441 strain HU1-3T 1429:1441 strain HU1-3T 1429:1441 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 10 25 theme HU1-3T 1259:1264 arg1 genome 1242:1247 the genome 1238:1247 the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides 1238:1356 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 10 26 dep glucosidase 1161:1171 arg1 e.g. 1156:1159 e.g. 1156:1159 e.g. 1156:1159 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 3 27 theme 16S 426:428 arg1 similarity 449:458 the highest 16S rRNA gene sequence similarity 414:458 the highest 16S rRNA gene sequence similarity 414:458 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 0 28 theme ulvae 15:19 arg1 sp 21:22 Hyunsoonleella ulvae sp 0:22 Hyunsoonleella ulvae sp. 0:23 Hyunsoonleella ulvae sp. 35511237 2 29 theme rod-shaped 111:120 arg1 strain 153:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain, designated HU1-3T, was isolated from Ulva in China. 35511237 3 30 theme Phylogenetic 213:224 arg1 analysis 226:233 Phylogenetic analysis 213:233 Phylogenetic analysis based on 16S rRNA gene sequences 213:266 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 9 31 theme polar 1097:1101 arg1 lipids 1103:1108 three unknown polar lipids 1083:1108 three unknown polar lipids 1083:1108 The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids, and three unknown polar lipids. 35511237 5 32 theme % 719:719 arg1 content 701:707 a G+C content 695:707 a G+C content of 33.9mol% 695:719 The draft genome of strain HU1-3T comprised 4.1 Mbp with a G+C content of 33.9mol%. 35511237 0 33 theme Hyunsoonleella 0:13 arg1 sp 21:22 Hyunsoonleella ulvae sp 0:22 Hyunsoonleella ulvae sp. 0:23 Hyunsoonleella ulvae sp. 35511237 6 34 theme strain 832:837 arg1 HU1-3T 839:844 strain HU1-3T 832:844 strain HU1-3T 832:844 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 13 35 theme type 1581:1584 arg1 HU1-3T 1596:1601 HU1-3T 1596:1601 HU1-3T (=KCTC 82511T=MCCC 1K05798T) 1596:1630 The type strain is HU1-3T (=KCTC 82511T=MCCC 1K05798T). 35511237 13 35 theme type 1581:1584 arg1 strain 1586:1591 The type strain 1577:1591 The type strain 1577:1591 The type strain is HU1-3T (=KCTC 82511T=MCCC 1K05798T). 35511237 10 36 theme Many 1111:1114 arg1 genes 1116:1120 Many genes 1111:1120 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) 1111:1218 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 10 36 theme Many 1111:1114 arg1 hydrolases 1144:1153 glycoside hydrolases 1134:1153 glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) 1134:1218 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 11 37 theme novel 1472:1476 arg1 species 1478:1484 a novel species 1470:1484 a novel species 1470:1484 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 8 38 theme respiratory 974:984 arg1 quinone 986:992 the major respiratory quinone 964:992 the major respiratory quinone 964:992 MK-6 was the major respiratory quinone. 35511237 8 38 theme respiratory 974:984 arg1 MK-6 955:958 MK-6 955:958 MK-6 955:958 MK-6 was the major respiratory quinone. 35511237 3 39 theme gene 253:256 arg1 sequences 258:266 16S rRNA gene sequences 244:266 16S rRNA gene sequences 244:266 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 9 40 theme major 999:1003 arg1 phosphatidylethanolamine 1023:1046 phosphatidylethanolamine 1023:1046 phosphatidylethanolamine 1023:1046 The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids, and three unknown polar lipids. 35511237 9 40 theme major 999:1003 arg1 lipids 1011:1016 The major polar lipids 995:1016 The major polar lipids 995:1016 The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids, and three unknown polar lipids. 35511237 3 41 theme sequence 440:447 arg1 similarity 449:458 the highest 16S rRNA gene sequence similarity 414:458 the highest 16S rRNA gene sequence similarity 414:458 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 3 42 theme family 356:361 arg1 Flavobacteriaceae 363:379 the family Flavobacteriaceae 352:379 the family Flavobacteriaceae 352:379 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 3 42 theme family 356:361 arg1 Bacteroidota 389:400 phylum Bacteroidota 382:400 phylum Bacteroidota 382:400 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 9 43 theme polar 1005:1009 arg1 phosphatidylethanolamine 1023:1046 phosphatidylethanolamine 1023:1046 phosphatidylethanolamine 1023:1046 The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids, and three unknown polar lipids. 35511237 9 43 theme polar 1005:1009 arg1 lipids 1011:1016 The major polar lipids 995:1016 The major polar lipids 995:1016 The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids, and three unknown polar lipids. 35511237 10 44 contain have 1297:1300 arg1 it 1288:1289 it 1288:1289 it 1288:1289 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 10 44 contain have 1297:1300 arg2 ability 1306:1312 the ability to degrade various kinds of polysaccharides 1302:1356 the ability to degrade various kinds of polysaccharides 1302:1356 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 5 45 theme draft 642:646 arg1 genome 648:653 The draft genome 638:653 The draft genome of strain HU1-3T 638:670 The draft genome of strain HU1-3T comprised 4.1 Mbp with a G+C content of 33.9mol%. 35511237 6 46 theme identity 814:821 arg1 value 823:827 the average nucleotide identity value 791:827 the average nucleotide identity value of strain HU1-3T 791:844 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 6 46 theme identity 814:821 arg1 % 855:855 77.9 % 850:855 77.9 % 850:855 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 3 47 theme 16S 244:246 arg1 sequences 258:266 16S rRNA gene sequences 244:266 16S rRNA gene sequences 244:266 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 5 48 theme G+C 697:699 arg1 content 701:707 a G+C content 695:707 a G+C content of 33.9mol% 695:719 The draft genome of strain HU1-3T comprised 4.1 Mbp with a G+C content of 33.9mol%. 35511237 3 49 theme rRNA 430:433 arg1 similarity 449:458 the highest 16S rRNA gene sequence similarity 414:458 the highest 16S rRNA gene sequence similarity 414:458 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 3 50 theme highest 418:424 arg1 similarity 449:458 the highest 16S rRNA gene sequence similarity 414:458 the highest 16S rRNA gene sequence similarity 414:458 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 6 51 theme nucleotide 803:812 arg1 value 823:827 the average nucleotide identity value 791:827 the average nucleotide identity value of strain HU1-3T 791:844 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 6 51 theme nucleotide 803:812 arg1 % 855:855 77.9 % 850:855 77.9 % 850:855 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 3 52 theme rRNA 248:251 arg1 sequences 258:266 16S rRNA gene sequences 244:266 16S rRNA gene sequences 244:266 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 11 53 theme genomic 1415:1421 arg1 data 1423:1426 the phylogenetic, chemotaxonomic, biochemical and genomic data 1365:1426 the phylogenetic, chemotaxonomic, biochemical and genomic data 1365:1426 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 11 54 theme Hyunsoonleella 1499:1512 arg1 species 1478:1484 a novel species 1470:1484 a novel species 1470:1484 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 7 55 theme major 862:866 arg1 acids 874:878 The major fatty acids 858:878 The major fatty acids (>10 % of the total) 858:899 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 7 55 theme major 862:866 arg1 iso-C15  906:913 iso-C15  906:913 iso-C15  906:913 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 3 56 theme gene 435:438 arg1 similarity 449:458 the highest 16S rRNA gene sequence similarity 414:458 the highest 16S rRNA gene sequence similarity 414:458 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 3 57 theme phylum 382:387 arg1 Flavobacteriaceae 363:379 the family Flavobacteriaceae 352:379 the family Flavobacteriaceae 352:379 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 3 57 theme phylum 382:387 arg1 Bacteroidota 389:400 phylum Bacteroidota 382:400 phylum Bacteroidota 382:400 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 2 58 theme Gram-stain-negative 69:87 arg1 strain 153:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain, designated HU1-3T, was isolated from Ulva in China. 35511237 3 59 theme strain 282:287 arg1 HU1-3T 289:294 strain HU1-3T 282:294 strain HU1-3T 282:294 Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HU1-3T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae, phylum Bacteroidota, and showed the highest 16S rRNA gene sequence similarity to Hyunsoonleella flava T58T (97.6 %). 35511237 4 60 dep optimum 531:537 arg1 25-30 °C 540:547 25-30 °C 540:547 25-30 °C 540:547 Strain HU1-3T grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %). 35511237 7 61 theme fatty 868:872 arg1 acids 874:878 The major fatty acids 858:878 The major fatty acids (>10 % of the total) 858:899 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 7 61 theme fatty 868:872 arg1 iso-C15  906:913 iso-C15  906:913 iso-C15  906:913 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 4 62 theme w/v 610:612 arg1 optimum 621:627 optimum 621:627 optimum 621:627 Strain HU1-3T grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %). 35511237 4 62 theme w/v 610:612 arg1 NaCl 615:618 2-6 % (w/v) NaCl 603:618 2-6 % (w/v) NaCl (optimum, 2-4 %) 603:635 Strain HU1-3T grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %). 35511237 5 63 theme strain 658:663 arg1 HU1-3T 665:670 strain HU1-3T 658:670 strain HU1-3T 658:670 The draft genome of strain HU1-3T comprised 4.1 Mbp with a G+C content of 33.9mol%. 35511237 2 64 theme novel 63:67 arg1 strain 153:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain 61:158 A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and yellow-pigmented bacterial strain, designated HU1-3T, was isolated from Ulva in China. 35511237 7 65 theme total 894:898 arg1 % 885:885 >10 % 881:885 >10 % 881:885 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 7 65 theme total 894:898 arg1 total 894:898 total 894:898 total 894:898 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 4 66 dep optimum 563:569 arg1 pH 572:573 pH 7.0 572:577 pH 7.0 572:577 Strain HU1-3T grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %). 35511237 10 67 theme various 1325:1331 arg1 kinds 1333:1337 various kinds 1325:1337 various kinds of polysaccharides 1325:1356 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 11 68 theme genus 1493:1497 arg1 Hyunsoonleella 1499:1512 the genus Hyunsoonleella 1489:1512 the genus Hyunsoonleella 1489:1512 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 4 69 theme NaCl 615:618 arg1 presence 591:598 the presence 587:598 the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %) 587:635 Strain HU1-3T grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %). 35511237 11 70 theme name 1529:1532 arg1 sp 1555:1556 the name Hyunsoonleella ulvae sp 1525:1556 the name Hyunsoonleella ulvae sp 1525:1556 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 7 71 dep iso-C15  906:913 arg1 iso-C17  937:944 iso-C17  937:944 iso-C17  937:944 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 7 71 dep iso-C15  906:913 arg1 3-OH 949:952  0 3-OH 946:952 iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH 906:952 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 7 71 dep iso-C15  906:913 arg1  1 930:931  1 930:931  1 930:931 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 7 71 dep iso-C15  906:913 arg1  0 915:916  0 915:916  0 915:916 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 7 71 dep iso-C15  906:913 arg1 G-C15  923:928 iso G-C15  919:928 iso G-C15  919:928 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 10 72 theme glycoside 1134:1142 arg1 genes 1116:1120 Many genes 1111:1120 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) 1111:1218 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 10 72 theme glycoside 1134:1142 arg1 hydrolases 1144:1153 glycoside hydrolases 1134:1153 glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) 1134:1218 Many genes that encode glycoside hydrolases (e.g. glucosidase, xylosidase, mannosidase, galactosidase, etc.) were annotated in the genome of strain HU1-3T, which indicated that it might have the ability to degrade various kinds of polysaccharides. 35511237 4 73 dep optimum 621:627 arg1 % 634:634 2-4 % 630:634 2-4 % 630:634 Strain HU1-3T grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 2-4 %). 35511237 7 74 dep acids 874:878 arg1 % 885:885 >10 % 881:885 >10 % 881:885 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 7 74 dep acids 874:878 arg1 total 894:898 total 894:898 total 894:898 The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1 and iso-C17 : 0 3-OH. 35511237 11 75 theme biochemical 1399:1409 arg1 data 1423:1426 the phylogenetic, chemotaxonomic, biochemical and genomic data 1365:1426 the phylogenetic, chemotaxonomic, biochemical and genomic data 1365:1426 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 5 76 theme 33.9mol 712:718 arg1 % 719:719 33.9mol% 712:719 33.9mol% 712:719 The draft genome of strain HU1-3T comprised 4.1 Mbp with a G+C content of 33.9mol%. 35511237 6 77 theme strain 750:755 arg1 CNU004T 782:788 the reference strain Hyunsoonleella jejuensis CNU004T 736:788 the reference strain Hyunsoonleella jejuensis CNU004T 736:788 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 11 78 theme phylogenetic 1369:1380 arg1 data 1423:1426 the phylogenetic, chemotaxonomic, biochemical and genomic data 1365:1426 the phylogenetic, chemotaxonomic, biochemical and genomic data 1365:1426 Given the phylogenetic, chemotaxonomic, biochemical and genomic data, strain HU1-3T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella ulvae sp. 35511237 8 79 theme major 968:972 arg1 quinone 986:992 the major respiratory quinone 964:992 the major respiratory quinone 964:992 MK-6 was the major respiratory quinone. 35511237 8 79 theme major 968:972 arg1 MK-6 955:958 MK-6 955:958 MK-6 955:958 MK-6 was the major respiratory quinone. 35511237 5 80 theme HU1-3T 665:670 arg1 genome 648:653 The draft genome 638:653 The draft genome of strain HU1-3T 638:670 The draft genome of strain HU1-3T comprised 4.1 Mbp with a G+C content of 33.9mol%. 35511237 6 81 theme average 795:801 arg1 value 823:827 the average nucleotide identity value 791:827 the average nucleotide identity value of strain HU1-3T 791:844 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 35511237 6 81 theme average 795:801 arg1 % 855:855 77.9 % 850:855 77.9 % 850:855 Compared with the reference strain Hyunsoonleella jejuensis CNU004T, the average nucleotide identity value of strain HU1-3T was 77.9 %. 36442206 3 0 theme controls 475:482 arg1 study 444:448 a community-based case-control study 413:448 a community-based case-control study of 96 PD patients and 74 controls, microbiome data 413:499 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 1 1 theme clinical 237:244 arg1 features 246:253 its clinical features 233:253 its clinical features 233:253 BACKGROUND Increasing evidence connects the gut microbiome to Parkinson's disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features. 36442206 9 2 theme bacterial 1860:1868 arg1 taxa 1870:1873 bacterial taxa 1860:1873 bacterial taxa 1860:1873 CONCLUSION PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression. 36442206 3 3 theme PD 669:670 arg1 patients 672:679 PD patients 669:679 PD patients 669:679 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 5 4 theme compound 1307:1314 arg1 degradation/utilization/assimilation 1316:1351 compound degradation/utilization/assimilation 1307:1351 compound degradation/utilization/assimilation 1307:1351 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 6 5 theme dysfunction 1457:1467 arg1 subtype 1469:1475 the postural instability gait dysfunction subtype 1427:1475 the postural instability gait dysfunction subtype 1427:1475 Additionally, the postural instability gait dysfunction subtype was associated with three phyla and the NAD biosynthesis. 36442206 9 6 theme metabolic 1887:1895 arg1 pathways 1897:1904 metabolic pathways 1887:1904 metabolic pathways of interest for PD progression 1887:1935 CONCLUSION PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression. 36442206 3 7 theme rRNA 525:528 arg1 sequencing 535:544 16 S rRNA gene sequencing 520:544 16 S rRNA gene sequencing of fecal samples 520:561 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 6 8 theme instability 1440:1450 arg1 subtype 1469:1475 the postural instability gait dysfunction subtype 1427:1475 the postural instability gait dysfunction subtype 1427:1475 Additionally, the postural instability gait dysfunction subtype was associated with three phyla and the NAD biosynthesis. 36442206 7 9 theme Synergistota 1571:1582 arg1 phylum 1584:1589 the Synergistota phylum 1567:1589 the Synergistota phylum 1567:1589 PD duration was associated with the Synergistota phylum, six genera, and the aromatic compound degradation pathways. 36442206 3 10 theme fecal 549:553 arg1 samples 555:561 fecal samples 549:561 fecal samples 549:561 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 4 11 theme gut 839:841 arg1 microbiome 843:852 PD patients' gut microbiome 826:852 PD patients' gut microbiome 826:852 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 3 12 theme microbial 581:589 arg1 diversity 591:599 microbial diversity 581:599 microbial diversity 581:599 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 4 13 dep genera 1067:1072 arg1 Hungatella 1102:1111 Hungatella 1102:1111 Hungatella 1102:1111 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 4 13 dep genera 1067:1072 arg1 Enterococcus 1088:1099 Enterococcus 1088:1099 Enterococcus 1088:1099 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 4 13 dep genera 1067:1072 arg1 Ruminococcaceae 1122:1136 Ruminococcaceae 1122:1136 Ruminococcaceae 1122:1136 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 4 13 dep genera 1067:1072 arg1 Akkermansia 1075:1085 Akkermansia 1075:1085 Akkermansia 1075:1085 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 7 14 theme PD 1535:1536 arg1 duration 1538:1545 PD duration 1535:1545 PD duration 1535:1545 PD duration was associated with the Synergistota phylum, six genera, and the aromatic compound degradation pathways. 36442206 3 15 theme community-based 415:429 arg1 study 444:448 a community-based case-control study 413:448 a community-based case-control study of 96 PD patients and 74 controls, microbiome data 413:499 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 16 theme disease 744:750 arg1 features 734:741 PD-specific features 722:741 PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function) 722:815 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 16 theme disease 744:750 arg1 duration 752:759 disease duration 744:759 disease duration 744:759 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 0 17 theme Rural 46:50 arg1 California 52:61 Rural California 46:61 Rural California 46:61 Parkinson's Disease and the Gut Microbiome in Rural California. 36442206 1 18 theme disease 138:144 arg1 etiology 151:158 Parkinson's disease (PD) etiology 126:158 Parkinson's disease (PD) etiology 126:158 BACKGROUND Increasing evidence connects the gut microbiome to Parkinson's disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features. 36442206 0 19 from Disease 12:18 arg1 California 52:61 Rural California 46:61 Rural California 46:61 Parkinson's Disease and the Gut Microbiome in Rural California. 36442206 3 20 theme L-DOPA 778:783 arg1 dose 791:794 L-DOPA daily dose 778:794 L-DOPA daily dose 778:794 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 20 theme L-DOPA 778:783 arg1 features 734:741 PD-specific features 722:741 PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function) 722:815 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 7 21 theme compound 1621:1628 arg1 pathways 1642:1649 the aromatic compound degradation pathways 1608:1649 the aromatic compound degradation pathways 1608:1649 PD duration was associated with the Synergistota phylum, six genera, and the aromatic compound degradation pathways. 36442206 0 22 from Microbiome 32:41 arg1 California 52:61 Rural California 46:61 Rural California 46:61 Parkinson's Disease and the Gut Microbiome in Rural California. 36442206 3 23 dep features 734:741 arg1 dose 791:794 L-DOPA daily dose 778:794 L-DOPA daily dose 778:794 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 23 dep features 734:741 arg1 features 734:741 PD-specific features 722:741 PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function) 722:815 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 23 dep features 734:741 arg1 duration 752:759 disease duration 744:759 disease duration 744:759 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 23 dep features 734:741 arg1 function 807:814 motor function 801:814 motor function 801:814 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 23 dep features 734:741 arg1 subtypes 768:775 motor subtypes 762:775 motor subtypes 762:775 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 0 24 theme Gut 28:30 arg1 Microbiome 32:41 the Gut Microbiome 24:41 the Gut Microbiome in Rural California 24:61 Parkinson's Disease and the Gut Microbiome in Rural California. 36442206 4 25 dep Proteobacteria 1007:1020 arg1 Actinobacteria 1042:1055 Actinobacteria 1042:1055 Actinobacteria 1042:1055 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 1 26 theme BACKGROUND 64:73 arg1 evidence 86:93 BACKGROUND Increasing evidence 64:93 BACKGROUND Increasing evidence 64:93 BACKGROUND Increasing evidence connects the gut microbiome to Parkinson's disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features. 36442206 5 27 theme glycan 1396:1401 arg1 pathways 1403:1410 glycan pathways 1396:1410 glycan pathways 1396:1410 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 9 28 theme microbiome 1753:1762 arg1 composition 1764:1774 gut microbiome composition 1749:1774 gut microbiome composition 1749:1774 CONCLUSION PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression. 36442206 4 29 theme sequencing 1175:1184 arg1 platform 1186:1193 sequencing platform 1175:1193 sequencing platform 1175:1193 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 2 30 theme PD-specific 371:381 arg1 features 392:399 PD-specific clinical features 371:399 PD-specific clinical features 371:399 OBJECTIVE We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. 36442206 9 31 theme predicted 1784:1792 arg1 metagenome 1794:1803 its predicted metagenome 1780:1803 its predicted metagenome 1780:1803 CONCLUSION PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression. 36442206 3 32 theme patients 459:466 arg1 study 444:448 a community-based case-control study 413:448 a community-based case-control study of 96 PD patients and 74 controls, microbiome data 413:499 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 4 33 theme phyla 1000:1004 arg1 abundance 981:989 a higher abundance 972:989 a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform 972:1193 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 3 34 theme functional 632:641 arg1 pathways 643:650 predicted functional pathways 622:650 predicted functional pathways that differed in PD patients and controls 622:692 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 1 35 theme microbial 187:195 arg1 contributions 197:209 microbial contributions 187:209 microbial contributions to PD progression and its clinical features 187:253 BACKGROUND Increasing evidence connects the gut microbiome to Parkinson's disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features. 36442206 3 36 from METHODS 402:408 arg1 study 444:448 a community-based case-control study 413:448 a community-based case-control study of 96 PD patients and 74 controls, microbiome data 413:499 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 4 37 theme higher 974:979 arg1 abundance 981:989 a higher abundance 972:989 a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform 972:1193 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 5 38 theme PD 1271:1272 arg1 pathways 1403:1410 glycan pathways 1396:1410 glycan pathways 1396:1410 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 5 38 theme PD 1271:1272 arg1 generation 1354:1363 generation 1354:1363 generation of metabolites and energy 1354:1389 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 5 38 theme PD 1271:1272 arg1 biosynthesis 1293:1304 biosynthesis 1293:1304 biosynthesis 1293:1304 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 5 38 theme PD 1271:1272 arg1 degradation/utilization/assimilation 1316:1351 compound degradation/utilization/assimilation 1307:1351 compound degradation/utilization/assimilation 1307:1351 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 5 38 theme PD 1271:1272 arg1 patients 1274:1281 PD patients 1271:1281 PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways 1271:1410 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 2 39 with association 354:364 arg1 PD 332:333 PD 332:333 PD 332:333 OBJECTIVE We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. 36442206 2 39 with association 354:364 arg1 features 392:399 PD-specific clinical features 371:399 PD-specific clinical features 371:399 OBJECTIVE We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. 36442206 5 40 theme metabolites 1368:1378 arg1 pathways 1403:1410 glycan pathways 1396:1410 glycan pathways 1396:1410 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 5 40 theme metabolites 1368:1378 arg1 biosynthesis 1293:1304 biosynthesis 1293:1304 biosynthesis 1293:1304 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 5 40 theme metabolites 1368:1378 arg1 generation 1354:1363 generation 1354:1363 generation of metabolites and energy 1354:1389 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 5 40 theme metabolites 1368:1378 arg1 degradation/utilization/assimilation 1316:1351 compound degradation/utilization/assimilation 1307:1351 compound degradation/utilization/assimilation 1307:1351 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 2 41 theme gut 312:314 arg1 microbiome 316:325 the gut microbiome 308:325 the gut microbiome 308:325 OBJECTIVE We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. 36442206 5 42 theme energy 1384:1389 arg1 pathways 1403:1410 glycan pathways 1396:1410 glycan pathways 1396:1410 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 5 42 theme energy 1384:1389 arg1 biosynthesis 1293:1304 biosynthesis 1293:1304 biosynthesis 1293:1304 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 5 42 theme energy 1384:1389 arg1 generation 1354:1363 generation 1354:1363 generation of metabolites and energy 1354:1389 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 5 42 theme energy 1384:1389 arg1 degradation/utilization/assimilation 1316:1351 compound degradation/utilization/assimilation 1307:1351 compound degradation/utilization/assimilation 1307:1351 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 4 43 theme genera 1067:1072 arg1 abundance 981:989 a higher abundance 972:989 a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform 972:1193 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 3 44 theme gene 530:533 arg1 sequencing 535:544 16 S rRNA gene sequencing 520:544 16 S rRNA gene sequencing of fecal samples 520:561 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 9 45 dep CONCLUSION 1700:1709 arg1 patients 1714:1721 PD patients 1711:1721 CONCLUSION PD patients 1700:1721 CONCLUSION PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression. 36442206 3 46 theme 16 S 520:523 arg1 sequencing 535:544 16 S rRNA gene sequencing 520:544 16 S rRNA gene sequencing of fecal samples 520:561 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 6 47 theme gait 1452:1455 arg1 subtype 1469:1475 the postural instability gait dysfunction subtype 1427:1475 the postural instability gait dysfunction subtype 1427:1475 Additionally, the postural instability gait dysfunction subtype was associated with three phyla and the NAD biosynthesis. 36442206 3 48 with diversity 591:599 arg1 dose 791:794 L-DOPA daily dose 778:794 L-DOPA daily dose 778:794 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 48 with diversity 591:599 arg1 features 734:741 PD-specific features 722:741 PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function) 722:815 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 48 with diversity 591:599 arg1 duration 752:759 disease duration 744:759 disease duration 744:759 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 48 with diversity 591:599 arg1 function 807:814 motor function 801:814 motor function 801:814 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 49 theme samples 555:561 arg1 sequencing 535:544 16 S rRNA gene sequencing 520:544 16 S rRNA gene sequencing of fecal samples 520:561 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 6 50 theme postural 1431:1438 arg1 subtype 1469:1475 the postural instability gait dysfunction subtype 1427:1475 the postural instability gait dysfunction subtype 1427:1475 Additionally, the postural instability gait dysfunction subtype was associated with three phyla and the NAD biosynthesis. 36442206 4 51 theme lower 861:865 arg1 species 867:873 lower species diversity (p = 0.04) 861:894 lower species diversity (p = 0.04) 861:894 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 9 52 theme interest 1909:1916 arg1 pathways 1897:1904 metabolic pathways 1887:1904 metabolic pathways of interest for PD progression 1887:1935 CONCLUSION PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression. 36442206 4 53 dep different 921:929 arg1 p = 0.002 932:940 p = 0.002 932:940 p = 0.002 932:940 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 1 54 theme gut 108:110 arg1 microbiome 112:121 the gut microbiome 104:121 the gut microbiome to Parkinson's disease (PD) etiology 104:158 BACKGROUND Increasing evidence connects the gut microbiome to Parkinson's disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features. 36442206 4 55 theme PD 826:827 arg1 patients 829:836 PD patients 826:836 PD patients' gut microbiome 826:852 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 9 56 theme PD 1922:1923 arg1 progression 1925:1935 PD progression 1922:1935 PD progression 1922:1935 CONCLUSION PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression. 36442206 3 57 theme PD-specific 722:732 arg1 dose 791:794 L-DOPA daily dose 778:794 L-DOPA daily dose 778:794 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 57 theme PD-specific 722:732 arg1 features 734:741 PD-specific features 722:741 PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function) 722:815 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 57 theme PD-specific 722:732 arg1 duration 752:759 disease duration 744:759 disease duration 744:759 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 57 theme PD-specific 722:732 arg1 function 807:814 motor function 801:814 motor function 801:814 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 6 58 theme NAD 1517:1519 arg1 biosynthesis 1521:1532 the NAD biosynthesis 1513:1532 the NAD biosynthesis 1513:1532 Additionally, the postural instability gait dysfunction subtype was associated with three phyla and the NAD biosynthesis. 36442206 3 59 theme motor 801:805 arg1 features 734:741 PD-specific features 722:741 PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function) 722:815 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 59 theme motor 801:805 arg1 function 807:814 motor function 801:814 motor function 801:814 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 2 60 dep explore 276:282 arg1 aim 269:271 aim 269:271 aim 269:271 OBJECTIVE We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. 36442206 3 61 theme motor 762:766 arg1 subtypes 768:775 motor subtypes 762:775 motor subtypes 762:775 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 9 62 theme PD 1711:1712 arg1 patients 1714:1721 PD patients 1711:1721 CONCLUSION PD patients 1700:1721 CONCLUSION PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression. 36442206 2 63 dep OBJECTIVE 256:264 arg1 We 266:267 We 266:267 We 266:267 OBJECTIVE We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. 36442206 3 64 theme daily 785:789 arg1 dose 791:794 L-DOPA daily dose 778:794 L-DOPA daily dose 778:794 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 64 theme daily 785:789 arg1 features 734:741 PD-specific features 722:741 PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function) 722:815 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 4 65 dep species 867:873 arg1 p = 0.04 886:893 p = 0.04 886:893 p = 0.04 886:893 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 4 65 dep species 867:873 arg1 diversity 875:883 diversity 875:883 lower species diversity (p = 0.04) 861:894 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 8 66 theme motor 1684:1688 arg1 function 1690:1697 motor function 1684:1697 motor function 1684:1697 Two genera were associated with motor function. 36442206 4 67 dep showed 854:859 arg1 had 968:970 had 968:970 had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform 968:1193 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 4 67 dep showed 854:859 arg1 different 921:929 different 921:929 different 921:929 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 7 68 theme degradation 1630:1640 arg1 pathways 1642:1649 the aromatic compound degradation pathways 1608:1649 the aromatic compound degradation pathways 1608:1649 PD duration was associated with the Synergistota phylum, six genera, and the aromatic compound degradation pathways. 36442206 2 69 theme microbial 344:352 arg1 association 354:364 the microbial association 340:364 the microbial association with PD-specific clinical features 340:399 OBJECTIVE We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. 36442206 1 70 theme Increasing 75:84 arg1 evidence 86:93 BACKGROUND Increasing evidence 64:93 BACKGROUND Increasing evidence 64:93 BACKGROUND Increasing evidence connects the gut microbiome to Parkinson's disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features. 36442206 7 71 theme aromatic 1612:1619 arg1 pathways 1642:1649 the aromatic compound degradation pathways 1608:1649 the aromatic compound degradation pathways 1608:1649 PD duration was associated with the Synergistota phylum, six genera, and the aromatic compound degradation pathways. 36442206 9 72 theme gut 1749:1751 arg1 composition 1764:1774 gut microbiome composition 1749:1774 gut microbiome composition 1749:1774 CONCLUSION PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression. 36442206 3 73 with association 705:715 arg1 dose 791:794 L-DOPA daily dose 778:794 L-DOPA daily dose 778:794 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 73 with association 705:715 arg1 features 734:741 PD-specific features 722:741 PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function) 722:815 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 73 with association 705:715 arg1 duration 752:759 disease duration 744:759 disease duration 744:759 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 73 with association 705:715 arg1 function 807:814 motor function 801:814 motor function 801:814 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 74 theme taxa 602:605 arg1 abundance 607:615 taxa abundance 602:615 taxa abundance 602:615 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 75 with abundance 607:615 arg1 dose 791:794 L-DOPA daily dose 778:794 L-DOPA daily dose 778:794 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 75 with abundance 607:615 arg1 features 734:741 PD-specific features 722:741 PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function) 722:815 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 75 with abundance 607:615 arg1 duration 752:759 disease duration 744:759 disease duration 744:759 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 75 with abundance 607:615 arg1 function 807:814 motor function 801:814 motor function 801:814 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 5 76 theme Metacyc 1205:1211 arg1 pathways 1213:1220 35 Metacyc pathways 1202:1220 35 Metacyc pathways 1202:1220 Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. 36442206 2 77 theme clinical 383:390 arg1 features 392:399 PD-specific clinical features 371:399 PD-specific clinical features 371:399 OBJECTIVE We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. 36442206 4 78 dep RESULTS 818:824 arg1 showed 854:859 showed 854:859 showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform 854:1193 RESULTS PD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. 36442206 2 79 with association 288:298 arg1 PD 332:333 PD 332:333 PD 332:333 OBJECTIVE We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. 36442206 2 79 with association 288:298 arg1 features 392:399 PD-specific clinical features 371:399 PD-specific clinical features 371:399 OBJECTIVE We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. 36442206 3 80 theme case-control 431:442 arg1 study 444:448 a community-based case-control study 413:448 a community-based case-control study of 96 PD patients and 74 controls, microbiome data 413:499 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 81 theme predicted 622:630 arg1 pathways 643:650 predicted functional pathways 622:650 predicted functional pathways that differed in PD patients and controls 622:692 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 82 theme PD 456:457 arg1 patients 459:466 96 PD patients 453:466 96 PD patients 453:466 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 82 theme PD 456:457 arg1 data 496:499 microbiome data 485:499 microbiome data 485:499 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 9 83 theme clinical 1816:1823 arg1 features 1825:1832 their clinical features 1810:1832 their clinical features 1810:1832 CONCLUSION PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression. 36442206 3 84 theme microbiome 485:494 arg1 patients 459:466 96 PD patients 453:466 96 PD patients 453:466 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 84 theme microbiome 485:494 arg1 data 496:499 microbiome data 485:499 microbiome data 485:499 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 85 with pathways 643:650 arg1 dose 791:794 L-DOPA daily dose 778:794 L-DOPA daily dose 778:794 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 85 with pathways 643:650 arg1 features 734:741 PD-specific features 722:741 PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function) 722:815 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 85 with pathways 643:650 arg1 duration 752:759 disease duration 744:759 disease duration 744:759 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 3 85 with pathways 643:650 arg1 function 807:814 motor function 801:814 motor function 801:814 METHODS In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). 36442206 1 86 theme PD 214:215 arg1 progression 217:227 PD progression 214:227 PD progression 214:227 BACKGROUND Increasing evidence connects the gut microbiome to Parkinson's disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features. 35318678 9 0 theme 1-OACs 1566:1571 arg1 lack 1558:1561 a lack 1556:1561 a lack of 1-OACs 1556:1571 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 4 1 theme in 577:578 arg1 maturation 586:595 in vitro maturation 577:595 in vitro maturation into reconstructed human epidermis 577:630 During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. 35318678 1 2 theme ceramide 257:264 arg1 group 244:248 the 1-hydroxyl of the sphingosine head group 205:248 the 1-hydroxyl of the sphingosine head group of the ceramide 205:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 1 2 theme ceramide 257:264 arg1 ceramide 257:264 the ceramide 253:264 the ceramide 253:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 4 3 theme 1-OAC 675:679 arg1 levels 681:686 1-OAC levels 675:686 1-OAC levels 675:686 During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. 35318678 3 4 theme 1-OACs 527:532 arg1 concentrate 534:544 1-OACs concentrate 527:544 1-OACs concentrate 527:544 Fractionation of human epidermis indicates 1-OACs concentrate in the stratum corneum. 35318678 8 5 from increase 1331:1338 arg1 1-OACs 1343:1348 1-OACs 1343:1348 1-OACs with N-linked non-hydroxylated fatty acids 1343:1391 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 9 6 dep deficiencies 1519:1530 arg1 we 1532:1533 we 1532:1533 we 1532:1533 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 8 7 with 1-OACs 1343:1348 arg1 acids 1387:1391 N-linked non-hydroxylated fatty acids 1355:1391 N-linked non-hydroxylated fatty acids 1355:1391 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 9 8 theme functional 1607:1616 arg1 redundancy 1618:1627 functional redundancy 1607:1627 functional redundancy 1607:1627 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 4 9 theme human 633:637 arg1 keratinocytes 639:651 human keratinocytes 633:651 human keratinocytes 633:651 During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. 35318678 3 10 theme stratum 553:559 arg1 corneum 561:567 the stratum corneum 549:567 the stratum corneum 549:567 Fractionation of human epidermis indicates 1-OACs concentrate in the stratum corneum. 35318678 6 11 theme mouse 1156:1160 arg1 model 1162:1166 any mouse model 1152:1166 any mouse model 1152:1166 Overall levels of 1-OACs did not decrease in any mouse model. 35318678 7 12 with correlation 1231:1241 arg1 function 1271:1278 deficient skin barrier function 1248:1278 deficient skin barrier function 1248:1278 In Cers3 and Dgat2-deficient epidermis they even increased in correlation with deficient skin barrier function. 35318678 4 13 dep in 577:578 arg1 vitro 580:584 vitro 580:584 vitro 580:584 During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. 35318678 1 14 theme 1-hydroxyl 209:218 arg1 group 244:248 the 1-hydroxyl of the sphingosine head group 205:248 the 1-hydroxyl of the sphingosine head group of the ceramide 205:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 1 14 theme 1-hydroxyl 209:218 arg1 ceramide 257:264 the ceramide 253:264 the ceramide 253:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 4 15 theme epidermal 722:730 arg1 1-OACs 732:737 epidermal 1-OACs 722:737 epidermal 1-OACs 722:737 During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. 35318678 8 16 theme % 1401:1401 arg1 decrease 1403:1410 a 60% decrease 1397:1410 a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate 1397:1487 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 5 17 theme cholesterol 1007:1017 arg1 Lcat 1036:1039 Lcat 1036:1039 Lcat 1036:1039 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 17 theme cholesterol 1007:1017 arg1 acyltransferase 1019:1033 lecithin cholesterol acyltransferase 998:1033 lecithin cholesterol acyltransferase (Lcat) 998:1040 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 18 theme acyltransferases 917:932 arg1 deficiencies 841:852 deficiencies 841:852 deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1) 841:1104 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 6 19 theme 1-OACs 1125:1130 arg1 levels 1115:1120 Overall levels 1107:1120 Overall levels of 1-OACs 1107:1130 Overall levels of 1-OACs did not decrease in any mouse model. 35318678 5 20 theme responsible 771:781 arg1 enzymes 763:769 potential enzymes 753:769 potential enzymes responsible for 1-OAC synthesis in vivo 753:809 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 1 21 theme natural 310:316 arg1 lipids 300:305 these lipids 294:305 these lipids 294:305 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 1 21 theme natural 310:316 arg1 components 318:327 natural components 310:327 natural components of human and mouse epidermis 310:356 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 0 22 theme barrier 84:90 arg1 establishment 44:56 the establishment 40:56 the establishment of the water permeability barrier in mice 40:98 Epidermal 1-O-acylceramides appear with the establishment of the water permeability barrier in mice and are produced by maturating keratinocytes. 35318678 5 23 from synthesis 793:801 arg1 vivo 806:809 vivo 806:809 vivo 806:809 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 24 theme stearoyl-CoA 1043:1054 arg1 desaturase 1056:1065 stearoyl-CoA desaturase 1 1043:1067 stearoyl-CoA desaturase 1 (Scd1) 1043:1074 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 24 theme stearoyl-CoA 1043:1054 arg1 Scd1 1070:1073 Scd1 1070:1073 Scd1 1070:1073 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 8 25 theme 1-OACs 1445:1450 arg1 levels 1435:1440 levels 1435:1440 levels of 1-OACs with N-linked hydroxylated palmitate 1435:1487 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 2 26 theme epidermal 372:380 arg1 1-OACs 382:387 epidermal 1-OACs 372:387 epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice 372:481 Here we show epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice. 35318678 5 27 theme potential 753:761 arg1 enzymes 763:769 potential enzymes 753:769 potential enzymes responsible for 1-OAC synthesis in vivo 753:809 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 7 28 theme barrier 1263:1269 arg1 function 1271:1278 deficient skin barrier function 1248:1278 deficient skin barrier function 1248:1278 In Cers3 and Dgat2-deficient epidermis they even increased in correlation with deficient skin barrier function. 35318678 8 29 theme N-linked 1457:1464 arg1 palmitate 1479:1487 N-linked hydroxylated palmitate 1457:1487 N-linked hydroxylated palmitate 1457:1487 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 0 30 theme permeability 71:82 arg1 barrier 84:90 the water permeability barrier 61:90 the water permeability barrier 61:90 Epidermal 1-O-acylceramides appear with the establishment of the water permeability barrier in mice and are produced by maturating keratinocytes. 35318678 8 31 theme 1-OAC 1307:1311 arg1 synthesis 1313:1321 1-OAC synthesis 1307:1321 1-OAC synthesis 1307:1321 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 0 32 theme Epidermal 0:8 arg1 1-O-acylceramides 10:26 Epidermal 1-O-acylceramides 0:26 Epidermal 1-O-acylceramides 0:26 Epidermal 1-O-acylceramides appear with the establishment of the water permeability barrier in mice and are produced by maturating keratinocytes. 35318678 7 33 theme deficient 1248:1256 arg1 function 1271:1278 deficient skin barrier function 1248:1278 deficient skin barrier function 1248:1278 In Cers3 and Dgat2-deficient epidermis they even increased in correlation with deficient skin barrier function. 35318678 1 34 dep human 332:336 arg1 epidermis 348:356 epidermis 348:356 epidermis 348:356 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 8 35 from control 1424:1430 arg1 levels 1435:1440 levels 1435:1440 levels of 1-OACs with N-linked hydroxylated palmitate 1435:1487 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 9 36 theme enzyme 1512:1517 arg1 deficiencies 1519:1530 the single enzyme deficiencies 1501:1530 the single enzyme deficiencies we examined 1501:1542 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 2 37 theme permeability 454:465 arg1 barrier 467:473 the water permeability barrier 444:473 the water permeability barrier 444:473 Here we show epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice. 35318678 0 38 theme water 65:69 arg1 barrier 84:90 the water permeability barrier 61:90 the water permeability barrier 61:90 Epidermal 1-O-acylceramides appear with the establishment of the water permeability barrier in mice and are produced by maturating keratinocytes. 35318678 5 39 theme acidic 1080:1085 arg1 Asah1 1099:1103 Asah1 1099:1103 Asah1 1099:1103 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 39 theme acidic 1080:1085 arg1 ceramidase 1087:1096 acidic ceramidase 1080:1096 acidic ceramidase (Asah1) 1080:1104 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 9 40 theme final 1748:1752 arg1 implications 1783:1794 the implications 1779:1794 the implications of which are discussed 1779:1817 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 9 40 theme final 1748:1752 arg1 step 1754:1757 the final step 1744:1757 the final step of 1-OAC synthesis 1744:1776 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 1 41 contain have 173:176 arg1 1-OACs 165:170 1-OACs 165:170 1-OACs 165:170 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 1 41 contain have 173:176 arg2 acid 186:189 a fatty acid 178:189 a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide 178:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 1 41 contain have 173:176 arg1 1-O-Acylceramides 146:162 1-O-Acylceramides 146:162 1-O-Acylceramides (1-OACs) 146:171 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 5 42 dep synthases 866:874 arg1 Cers3 884:888 Cers3 884:888 Cers3 884:888 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 42 dep synthases 866:874 arg1 Cers4 894:898 Cers4 894:898 Cers4 894:898 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 42 dep synthases 866:874 arg1 Cers2 877:881 Cers2 877:881 Cers2 877:881 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 42 dep synthases 866:874 arg1 synthases 866:874 ceramide synthases 857:874 ceramide synthases (Cers2, Cers3, or Cers4) 857:899 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 8 43 theme N-linked 1355:1362 arg1 acids 1387:1391 N-linked non-hydroxylated fatty acids 1355:1391 N-linked non-hydroxylated fatty acids 1355:1391 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 1 44 theme of 220:221 arg1 group 244:248 the 1-hydroxyl of the sphingosine head group 205:248 the 1-hydroxyl of the sphingosine head group of the ceramide 205:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 1 44 theme of 220:221 arg1 ceramide 257:264 the ceramide 253:264 the ceramide 253:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 5 45 theme long 969:972 arg1 acids 980:984 very long fatty acids 3 (Elovl3) 964:995 very long fatty acids 3 (Elovl3) 964:995 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 7 46 theme Dgat2-deficient 1182:1196 arg1 epidermis 1198:1206 Cers3 and Dgat2-deficient epidermis 1172:1206 Cers3 and Dgat2-deficient epidermis 1172:1206 In Cers3 and Dgat2-deficient epidermis they even increased in correlation with deficient skin barrier function. 35318678 9 47 theme synthesis 1768:1776 arg1 implications 1783:1794 the implications 1779:1794 the implications of which are discussed 1779:1817 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 9 47 theme synthesis 1768:1776 arg1 step 1754:1757 the final step 1744:1757 the final step of 1-OAC synthesis 1744:1776 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 8 48 theme fatty 1381:1385 arg1 acids 1387:1391 N-linked non-hydroxylated fatty acids 1355:1391 N-linked non-hydroxylated fatty acids 1355:1391 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 3 49 theme human 501:505 arg1 epidermis 507:515 human epidermis 501:515 human epidermis 501:515 Fractionation of human epidermis indicates 1-OACs concentrate in the stratum corneum. 35318678 1 50 theme sphingosine 227:237 arg1 group 244:248 the 1-hydroxyl of the sphingosine head group 205:248 the 1-hydroxyl of the sphingosine head group of the ceramide 205:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 1 50 theme sphingosine 227:237 arg1 ceramide 257:264 the ceramide 253:264 the ceramide 253:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 5 51 theme acids 980:984 arg1 Asah1 1099:1103 Asah1 1099:1103 Asah1 1099:1103 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 acyltransferases 917:932 diacylglycerol acyltransferases 902:932 diacylglycerol acyltransferases (Dgat1 or Dgat2) 902:949 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 Cers3 884:888 Cers3 884:888 Cers3 884:888 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 acyltransferase 1019:1033 lecithin cholesterol acyltransferase 998:1033 lecithin cholesterol acyltransferase (Lcat) 998:1040 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 elongase 952:959 elongase 952:959 elongase of very long fatty acids 3 (Elovl3) 952:995 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 desaturase 1056:1065 stearoyl-CoA desaturase 1 1043:1067 stearoyl-CoA desaturase 1 (Scd1) 1043:1074 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 Cers4 894:898 Cers4 894:898 Cers4 894:898 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 ceramidase 1087:1096 acidic ceramidase 1080:1096 acidic ceramidase (Asah1) 1080:1104 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 synthases 866:874 ceramide synthases 857:874 ceramide synthases (Cers2, Cers3, or Cers4) 857:899 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 Lcat 1036:1039 Lcat 1036:1039 Lcat 1036:1039 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 Dgat2 944:948 Dgat2 944:948 Dgat2 944:948 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 Cers2 877:881 Cers2 877:881 Cers2 877:881 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 Scd1 1070:1073 Scd1 1070:1073 Scd1 1070:1073 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 51 theme acids 980:984 arg1 Dgat1 935:939 Dgat1 935:939 Dgat1 935:939 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 7 52 theme Cers3 1172:1176 arg1 epidermis 1198:1206 Cers3 and Dgat2-deficient epidermis 1172:1206 Cers3 and Dgat2-deficient epidermis 1172:1206 In Cers3 and Dgat2-deficient epidermis they even increased in correlation with deficient skin barrier function. 35318678 4 53 theme human 616:620 arg1 epidermis 622:630 reconstructed human epidermis 602:630 reconstructed human epidermis 602:630 During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. 35318678 6 54 theme Overall 1107:1113 arg1 levels 1115:1120 Overall levels 1107:1120 Overall levels of 1-OACs 1107:1130 Overall levels of 1-OACs did not decrease in any mouse model. 35318678 5 55 theme synthases 866:874 arg1 deficiencies 841:852 deficiencies 841:852 deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1) 841:1104 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 56 theme 1-OAC 787:791 arg1 synthesis 793:801 1-OAC synthesis 787:801 1-OAC synthesis in vivo 787:809 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 1 57 theme fatty 180:184 arg1 acid 186:189 a fatty acid 178:189 a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide 178:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 5 58 with mice 831:834 arg1 deficiencies 841:852 deficiencies 841:852 deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1) 841:1104 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 0 59 theme maturating 120:129 arg1 keratinocytes 131:143 maturating keratinocytes 120:143 maturating keratinocytes 120:143 Epidermal 1-O-acylceramides appear with the establishment of the water permeability barrier in mice and are produced by maturating keratinocytes. 35318678 5 60 dep acids 980:984 arg1 Elovl3 989:994 Elovl3 989:994 Elovl3 989:994 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 60 dep acids 980:984 arg1 3 986:986 3 986:986 3 986:986 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 8 61 theme 60 1399:1400 arg1 % 1401:1401 % 1401:1401 % 1401:1401 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 5 62 theme lecithin 998:1005 arg1 Lcat 1036:1039 Lcat 1036:1039 Lcat 1036:1039 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 62 theme lecithin 998:1005 arg1 acyltransferase 1019:1033 lecithin cholesterol acyltransferase 998:1033 lecithin cholesterol acyltransferase (Lcat) 998:1040 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 63 theme diacylglycerol 902:915 arg1 Dgat2 944:948 Dgat2 944:948 Dgat2 944:948 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 63 theme diacylglycerol 902:915 arg1 Dgat1 935:939 Dgat1 935:939 Dgat1 935:939 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 63 theme diacylglycerol 902:915 arg1 acyltransferases 917:932 diacylglycerol acyltransferases 902:932 diacylglycerol acyltransferases (Dgat1 or Dgat2) 902:949 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 4 64 theme 1-OACs 732:737 arg1 they 699:702 they 699:702 they 699:702 During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. 35318678 4 64 theme 1-OACs 732:737 arg1 source 712:717 one source 708:717 one source of epidermal 1-OACs 708:737 During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. 35318678 5 65 theme enzymes 763:769 arg1 search 743:748 search 743:748 search of potential enzymes responsible for 1-OAC synthesis in vivo 743:809 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 66 theme acyltransferase 1019:1033 arg1 deficiencies 841:852 deficiencies 841:852 deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1) 841:1104 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 2 67 theme barrier 467:473 arg1 establishment 427:439 the establishment 423:439 the establishment of the water permeability barrier in mice 423:481 Here we show epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice. 35318678 2 68 from establishment 427:439 arg1 mice 478:481 mice 478:481 mice 478:481 Here we show epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice. 35318678 1 69 theme human 332:336 arg1 lipids 300:305 these lipids 294:305 these lipids 294:305 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 1 69 theme human 332:336 arg1 components 318:327 natural components 310:327 natural components of human and mouse epidermis 310:356 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 8 70 link N-linked 1355:1362 arg1 acids 1387:1391 N-linked non-hydroxylated fatty acids 1355:1391 N-linked non-hydroxylated fatty acids 1355:1391 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 5 71 dep acyltransferases 917:932 arg1 Dgat2 944:948 Dgat2 944:948 Dgat2 944:948 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 71 dep acyltransferases 917:932 arg1 Dgat1 935:939 Dgat1 935:939 Dgat1 935:939 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 71 dep acyltransferases 917:932 arg1 acyltransferases 917:932 diacylglycerol acyltransferases 902:932 diacylglycerol acyltransferases (Dgat1 or Dgat2) 902:949 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 8 72 from decrease 1403:1410 arg1 1-OACs 1343:1348 1-OACs 1343:1348 1-OACs with N-linked non-hydroxylated fatty acids 1343:1391 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 1 73 theme mouse 342:346 arg1 lipids 300:305 these lipids 294:305 these lipids 294:305 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 1 73 theme mouse 342:346 arg1 components 318:327 natural components 310:327 natural components of human and mouse epidermis 310:356 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 5 74 theme elongase 952:959 arg1 deficiencies 841:852 deficiencies 841:852 deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1) 841:1104 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 7 75 theme skin 1258:1261 arg1 function 1271:1278 deficient skin barrier function 1248:1278 deficient skin barrier function 1248:1278 In Cers3 and Dgat2-deficient epidermis they even increased in correlation with deficient skin barrier function. 35318678 9 76 theme unknown 1694:1700 arg1 acyltransferase 1702:1716 an unknown acyltransferase 1691:1716 an unknown acyltransferase of the epidermis 1691:1733 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 0 77 from establishment 44:56 arg1 mice 95:98 mice 95:98 mice 95:98 Epidermal 1-O-acylceramides appear with the establishment of the water permeability barrier in mice and are produced by maturating keratinocytes. 35318678 8 78 theme Dagt2 1281:1285 arg1 deficiency 1287:1296 Dagt2 deficiency 1281:1296 Dagt2 deficiency 1281:1296 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 5 79 theme desaturase 1056:1065 arg1 deficiencies 841:852 deficiencies 841:852 deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1) 841:1104 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 80 theme mutant 824:829 arg1 mice 831:834 mutant mice 824:834 mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1) 824:1104 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 9 81 theme single 1505:1510 arg1 deficiencies 1519:1530 the single enzyme deficiencies 1501:1530 the single enzyme deficiencies we examined 1501:1542 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 9 82 theme epidermis 1725:1733 arg1 acyltransferase 1702:1716 an unknown acyltransferase 1691:1716 an unknown acyltransferase of the epidermis 1691:1733 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 9 83 theme deficiencies 1519:1530 arg1 none 1493:1496 none 1493:1496 none of the single enzyme deficiencies we examined 1493:1542 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 2 84 theme water 448:452 arg1 barrier 467:473 the water permeability barrier 444:473 the water permeability barrier 444:473 Here we show epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice. 35318678 2 85 dep 1-OACs 382:387 arg1 arise 389:393 arise 389:393 arise shortly before birth during the establishment of the water permeability barrier in mice 389:481 Here we show epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice. 35318678 8 86 with 1-OACs 1445:1450 arg1 palmitate 1479:1487 N-linked hydroxylated palmitate 1457:1487 N-linked hydroxylated palmitate 1457:1487 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 5 87 theme ceramidase 1087:1096 arg1 deficiencies 841:852 deficiencies 841:852 deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1) 841:1104 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 8 88 theme hydroxylated 1466:1477 arg1 palmitate 1479:1487 N-linked hydroxylated palmitate 1457:1487 N-linked hydroxylated palmitate 1457:1487 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 9 89 theme 1-OAC 1762:1766 arg1 synthesis 1768:1776 1-OAC synthesis 1762:1776 1-OAC synthesis 1762:1776 As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed. 35318678 4 90 theme reconstructed 602:614 arg1 epidermis 622:630 reconstructed human epidermis 602:630 reconstructed human epidermis 602:630 During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. 35318678 8 91 link N-linked 1457:1464 arg1 palmitate 1479:1487 N-linked hydroxylated palmitate 1457:1487 N-linked hydroxylated palmitate 1457:1487 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 5 92 theme ceramide 857:864 arg1 Cers3 884:888 Cers3 884:888 Cers3 884:888 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 92 theme ceramide 857:864 arg1 Cers4 894:898 Cers4 894:898 Cers4 894:898 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 92 theme ceramide 857:864 arg1 Cers2 877:881 Cers2 877:881 Cers2 877:881 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 92 theme ceramide 857:864 arg1 synthases 866:874 ceramide synthases 857:874 ceramide synthases (Cers2, Cers3, or Cers4) 857:899 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 5 93 theme fatty 974:978 arg1 acids 980:984 very long fatty acids 3 (Elovl3) 964:995 very long fatty acids 3 (Elovl3) 964:995 In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). 35318678 8 94 theme non-hydroxylated 1364:1379 arg1 acids 1387:1391 N-linked non-hydroxylated fatty acids 1355:1391 N-linked non-hydroxylated fatty acids 1355:1391 Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. 35318678 3 95 theme epidermis 507:515 arg1 Fractionation 484:496 Fractionation 484:496 Fractionation of human epidermis 484:515 Fractionation of human epidermis indicates 1-OACs concentrate in the stratum corneum. 35318678 1 96 theme head 239:242 arg1 group 244:248 the 1-hydroxyl of the sphingosine head group 205:248 the 1-hydroxyl of the sphingosine head group of the ceramide 205:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35318678 1 96 theme head 239:242 arg1 ceramide 257:264 the ceramide 253:264 the ceramide 253:264 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. 35350184 9 0 theme heavy 1681:1685 arg1 NGHC 1694:1697 NGHC 1694:1697 NGHC 1694:1697 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 0 theme heavy 1681:1685 arg1 chain 1687:1691 the non-glycosylated heavy chain 1660:1691 the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE) 1660:1717 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 7 1 theme therapeutics 1219:1230 arg1 function 1198:1205 The effector function 1185:1205 The effector function of antibody therapeutics 1185:1230 The effector function of antibody therapeutics is greatly affected by their N-linked carbohydrates at the conserved Fc region, possibly influenced by the manufacturing process. 35350184 9 2 gly non-glycosylated 1664:1679 arg1 NGHC 1694:1697 NGHC 1694:1697 NGHC 1694:1697 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 2 gly non-glycosylated 1664:1679 arg1 chain 1687:1691 the non-glycosylated heavy chain 1660:1691 the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE) 1660:1717 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 3 3 theme protein 527:533 arg1 protein 527:533 the Spike protein 517:533 the Spike protein expressed on the surface of the virus 517:571 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 3 3 theme protein 527:533 arg1 RBD 509:511 RBD 509:511 RBD 509:511 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 3 3 theme protein 527:533 arg1 domain 501:506 The receptor-binding domain 480:506 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus 480:571 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 11 4 theme core-afucosylated 2190:2206 arg1 complex 2208:2214 approximately 8.2% core-afucosylated complex 2171:2214 approximately 8.2% core-afucosylated complex 2171:2214 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 6 5 theme related 1147:1153 arg1 activity 1155:1162 its effector function related activity 1125:1162 its effector function related activity 1125:1162 Albeit, bamlanivimab is primarily a neutralizing mAb, some of its effector function related activity was also emphasized. 35350184 9 6 theme excess 1842:1847 arg1 sialylation 1849:1859 excess sialylation 1842:1859 excess sialylation 1842:1859 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 7 dep determine 1626:1634 arg1 1 1592:1592 1 1592:1592 1 1592:1592 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 11 8 theme galactosylated 2224:2237 arg1 oligosaccharides 2248:2263 galactosylated N-linked oligosaccharides 2224:2263 galactosylated N-linked oligosaccharides 2224:2263 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 6 9 theme effector 1129:1136 arg1 function 1138:1145 its effector function 1125:1145 its effector function 1125:1145 Albeit, bamlanivimab is primarily a neutralizing mAb, some of its effector function related activity was also emphasized. 35350184 10 10 theme amount 2003:2008 arg1 presence 1980:1987 the presence 1976:1987 the presence of negligible amount of non-glycosylated heavy chain (NGHC) 1976:2047 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 4 11 theme promising 878:886 arg1 strategy 904:911 a promising pharmacological strategy 876:911 a promising pharmacological strategy 876:911 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 0 12 theme N-Glycosylation 119:133 arg1 Analysis 143:150 N-Glycosylation Variant Analysis 119:150 N-Glycosylation Variant Analysis 119:150 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 5 13 theme COVID-19 1043:1050 arg1 treatment 1052:1060 COVID-19 treatment 1043:1060 COVID-19 treatment 1043:1060 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 11 14 theme neutralizing 2414:2425 arg1 effect 2427:2432 the generally considered neutralizing effect 2389:2432 the generally considered neutralizing effect of this particular therapeutic antibody molecule 2389:2481 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 11 15 dep % 2188:2188 arg1 8.2 2185:2187 8.2 2185:2187 8.2 2185:2187 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 10 16 theme chain 2036:2040 arg1 amount 2003:2008 negligible amount 1992:2008 negligible amount of non-glycosylated heavy chain (NGHC) 1992:2047 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 10 16 theme chain 2036:2040 arg1 NGHC 2043:2046 NGHC 2043:2046 NGHC 2043:2046 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 10 16 theme chain 2036:2040 arg1 chain 2036:2040 non-glycosylated heavy chain 2013:2040 non-glycosylated heavy chain (NGHC) 2013:2047 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 9 17 theme capillary 1723:1731 arg1 gel 1733:1735 a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel 1541:1735 a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing 1541:1756 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 11 18 theme Comprehensive 2097:2109 arg1 characterization 2127:2142 Comprehensive N-glycosylation characterization 2097:2142 Comprehensive N-glycosylation characterization 2097:2142 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 11 19 dep complex 2208:2214 arg1 oligosaccharides 2248:2263 galactosylated N-linked oligosaccharides 2224:2263 galactosylated N-linked oligosaccharides 2224:2263 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 11 19 dep complex 2208:2214 arg1 % 2188:2188 % 2188:2188 % 2188:2188 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 10 20 theme non-glycosylated 2013:2028 arg1 NGHC 2043:2046 NGHC 2043:2046 NGHC 2043:2046 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 10 20 theme non-glycosylated 2013:2028 arg1 chain 2036:2040 non-glycosylated heavy chain 2013:2040 non-glycosylated heavy chain (NGHC) 2013:2047 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 0 21 theme Bamlanivimab 155:166 arg1 Analysis 143:150 N-Glycosylation Variant Analysis 119:150 N-Glycosylation Variant Analysis 119:150 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 0 21 theme Bamlanivimab 155:166 arg1 Charge 107:112 Charge 107:112 Charge 107:112 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 0 21 theme Bamlanivimab 155:166 arg1 Product 188:194 an Anti-SARS-CoV-2 Product 169:194 an Anti-SARS-CoV-2 Product 169:194 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 0 21 theme Bamlanivimab 155:166 arg1 Size 101:104 Size 101:104 Size 101:104 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 7 22 link N-linked 1261:1268 arg1 carbohydrates 1270:1282 their N-linked carbohydrates 1255:1282 their N-linked carbohydrates 1255:1282 The effector function of antibody therapeutics is greatly affected by their N-linked carbohydrates at the conserved Fc region, possibly influenced by the manufacturing process. 35350184 7 23 theme manufacturing 1339:1351 arg1 process 1353:1359 the manufacturing process 1335:1359 the manufacturing process 1335:1359 The effector function of antibody therapeutics is greatly affected by their N-linked carbohydrates at the conserved Fc region, possibly influenced by the manufacturing process. 35350184 4 24 theme monoclonal 691:700 arg1 antibodies 702:711 Neutralizing monoclonal antibodies 678:711 Neutralizing monoclonal antibodies having the RBD as a target 678:738 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 8 25 theme antibodies 1502:1511 arg1 characterization 1470:1485 the characterization 1466:1485 the characterization of therapeutic antibodies 1466:1511 Various capillary gel electrophoresis methods are widely accepted in the biopharmaceutical industry for the characterization of therapeutic antibodies. 35350184 7 26 theme antibody 1210:1217 arg1 therapeutics 1219:1230 antibody therapeutics 1210:1230 antibody therapeutics 1210:1230 The effector function of antibody therapeutics is greatly affected by their N-linked carbohydrates at the conserved Fc region, possibly influenced by the manufacturing process. 35350184 3 27 theme key 581:583 arg1 role 585:588 a key role 579:588 a key role 579:588 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 9 28 theme N-glycosylation 1771:1785 arg1 heterogeneity 1803:1815 possible N-glycosylation mediated charge heterogeneity 1762:1815 possible N-glycosylation mediated charge heterogeneity determination 1762:1829 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 11 29 theme N-glycosylation 2111:2125 arg1 characterization 2127:2142 Comprehensive N-glycosylation characterization 2097:2142 Comprehensive N-glycosylation characterization 2097:2142 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 10 30 theme charge 2066:2071 arg1 variants 2073:2080 25% acidic charge variants 2055:2080 25% acidic charge variants 2055:2080 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 9 31 theme gel 1553:1555 arg1 electrophoresis 1557:1571 capillary gel electrophoresis 1543:1571 a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing 1541:1756 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 32 theme charge 1796:1801 arg1 heterogeneity 1803:1815 possible N-glycosylation mediated charge heterogeneity 1762:1815 possible N-glycosylation mediated charge heterogeneity determination 1762:1829 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 11 33 theme molecule 2474:2481 arg1 effect 2427:2432 the generally considered neutralizing effect 2389:2432 the generally considered neutralizing effect of this particular therapeutic antibody molecule 2389:2481 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 9 34 dep focusing 1749:1756 arg1 isoelectric 1737:1747 isoelectric 1737:1747 isoelectric 1737:1747 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 5 35 theme anti-spike 940:949 arg1 antibody 975:982 the first anti-spike neutralizing monoclonal antibody 930:982 the first anti-spike neutralizing monoclonal antibody 930:982 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 5 35 theme anti-spike 940:949 arg1 Bamlanivimab 914:925 Bamlanivimab 914:925 Bamlanivimab 914:925 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 11 36 theme antibody 2303:2310 arg1 cell 2322:2325 antibody dependent cell 2303:2325 antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule 2303:2481 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 11 37 theme therapeutic 2453:2463 arg1 molecule 2474:2481 this particular therapeutic antibody molecule 2437:2481 this particular therapeutic antibody molecule 2437:2481 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 1 38 theme publication 355:365 arg1 time 342:345 the time 338:345 the time of this publication 338:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 5 39 theme monoclonal 964:973 arg1 antibody 975:982 the first anti-spike neutralizing monoclonal antibody 930:982 the first anti-spike neutralizing monoclonal antibody 930:982 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 5 39 theme monoclonal 964:973 arg1 Bamlanivimab 914:925 Bamlanivimab 914:925 Bamlanivimab 914:925 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 2 40 theme Syndrome 443:450 arg1 Coronavirus 452:462 Severe Acute Respiratory Syndrome Coronavirus 2 418:464 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 418:477 The disease is caused by a betacoronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). 35350184 2 40 theme Syndrome 443:450 arg1 SARS-CoV-2 467:476 SARS-CoV-2 467:476 SARS-CoV-2 467:476 The disease is caused by a betacoronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). 35350184 8 41 theme Various 1362:1368 arg1 methods 1400:1406 Various capillary gel electrophoresis methods 1362:1406 Various capillary gel electrophoresis methods 1362:1406 Various capillary gel electrophoresis methods are widely accepted in the biopharmaceutical industry for the characterization of therapeutic antibodies. 35350184 1 42 theme 5-10 281:284 arg1 % 285:285 % 285:285 % 285:285 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 9 43 dep electrophoresis 1891:1905 arg1 e.g. 1832:1835 e.g. 1832:1835 e.g. 1832:1835 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 43 dep electrophoresis 1891:1905 arg1 3 1874:1874 3 1874:1874 3 1874:1874 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 2 44 theme Acute 425:429 arg1 Coronavirus 452:462 Severe Acute Respiratory Syndrome Coronavirus 2 418:464 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 418:477 The disease is caused by a betacoronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). 35350184 2 44 theme Acute 425:429 arg1 SARS-CoV-2 467:476 SARS-CoV-2 467:476 SARS-CoV-2 467:476 The disease is caused by a betacoronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). 35350184 8 45 theme gel 1380:1382 arg1 electrophoresis 1384:1398 capillary gel electrophoresis 1370:1398 Various capillary gel electrophoresis methods 1362:1406 Various capillary gel electrophoresis methods are widely accepted in the biopharmaceutical industry for the characterization of therapeutic antibodies. 35350184 1 46 theme hospitalization 287:301 arg1 rates 329:333 5-10% hospitalization and 2-3% global mortality rates 281:333 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 281:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 9 47 theme heterogeneity 1600:1612 arg1 analysis 1614:1621 size heterogeneity analysis 1595:1621 size heterogeneity analysis 1595:1621 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 7 48 theme Fc 1301:1302 arg1 region 1304:1309 the conserved Fc region 1287:1309 the conserved Fc region 1287:1309 The effector function of antibody therapeutics is greatly affected by their N-linked carbohydrates at the conserved Fc region, possibly influenced by the manufacturing process. 35350184 0 49 theme Biotherapeutics 67:81 arg1 Characterization 83:98 Biotherapeutics Characterization 67:98 Biotherapeutics Characterization 67:98 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 4 50 theme enzyme 791:796 arg1 binding 816:822 angiotensin-converting enzyme 2 (ACE2) receptor binding 768:822 angiotensin-converting enzyme 2 (ACE2) receptor binding 768:822 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 0 51 theme Gel 28:30 arg1 Workflow 54:61 a Capillary Gel Electrophoresis-Based Workflow 16:61 a Capillary Gel Electrophoresis-Based Workflow 16:61 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 1 52 from time 342:345 arg1 rates 329:333 5-10% hospitalization and 2-3% global mortality rates 281:333 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 281:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 5 53 theme emergency 998:1006 arg1 authorization 1012:1024 an emergency use authorization 995:1024 an emergency use authorization from the FDA for COVID-19 treatment 995:1060 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 1 54 with worldwide 266:274 arg1 rates 329:333 5-10% hospitalization and 2-3% global mortality rates 281:333 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 281:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 11 55 theme N-linked 2239:2246 arg1 oligosaccharides 2248:2263 galactosylated N-linked oligosaccharides 2224:2263 galactosylated N-linked oligosaccharides 2224:2263 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 3 56 theme viral 597:601 arg1 entry 603:607 the viral entry 593:607 the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor 593:675 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 0 57 theme Workflow 54:61 arg1 Introduction 0:11 Introduction 0:11 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 0:195 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 1 58 theme global 312:317 arg1 rates 329:333 5-10% hospitalization and 2-3% global mortality rates 281:333 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 281:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 11 59 theme complex 2208:2214 arg1 occurrence 2157:2166 the occurrence 2153:2166 the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides 2153:2263 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 10 60 theme heavy 2030:2034 arg1 NGHC 2043:2046 NGHC 2043:2046 NGHC 2043:2046 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 10 60 theme heavy 2030:2034 arg1 chain 2036:2040 non-glycosylated heavy chain 2013:2040 non-glycosylated heavy chain (NGHC) 2013:2047 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 4 61 theme angiotensin-converting 768:789 arg1 enzyme 791:796 angiotensin-converting enzyme 2 768:798 angiotensin-converting enzyme 2 (ACE2) receptor binding 768:822 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 4 61 theme angiotensin-converting 768:789 arg1 ACE2 801:804 ACE2 801:804 ACE2 801:804 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 9 62 theme non-glycosylated 1664:1679 arg1 NGHC 1694:1697 NGHC 1694:1697 NGHC 1694:1697 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 62 theme non-glycosylated 1664:1679 arg1 chain 1687:1691 the non-glycosylated heavy chain 1660:1691 the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE) 1660:1717 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 63 theme capillary 1877:1885 arg1 electrophoresis 1891:1905 capillary gel electrophoresis 1877:1905 3) capillary gel electrophoresis for N-glycosylation profiling 1874:1935 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 3 64 theme host 618:621 arg1 cell 623:626 the host cell 614:626 the host cell 614:626 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 8 65 theme biopharmaceutical 1435:1451 arg1 industry 1453:1460 the biopharmaceutical industry 1431:1460 the biopharmaceutical industry for the characterization of therapeutic antibodies 1431:1511 Various capillary gel electrophoresis methods are widely accepted in the biopharmaceutical industry for the characterization of therapeutic antibodies. 35350184 1 66 theme major 238:242 arg1 problem 258:264 a major public health problem 236:264 a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 236:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 1 66 theme major 238:242 arg1 Disease 209:215 Coronavirus Disease 2019 197:220 Coronavirus Disease 2019 (COVID-19) 197:231 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 0 67 dep Introduction 0:11 arg1 Analysis 143:150 N-Glycosylation Variant Analysis 119:150 N-Glycosylation Variant Analysis 119:150 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 0 67 dep Introduction 0:11 arg1 Charge 107:112 Charge 107:112 Charge 107:112 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 0 67 dep Introduction 0:11 arg1 Product 188:194 an Anti-SARS-CoV-2 Product 169:194 an Anti-SARS-CoV-2 Product 169:194 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 0 67 dep Introduction 0:11 arg1 Size 101:104 Size 101:104 Size 101:104 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 1 68 theme health 251:256 arg1 problem 258:264 a major public health problem 236:264 a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 236:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 1 68 theme health 251:256 arg1 Disease 209:215 Coronavirus Disease 2019 197:220 Coronavirus Disease 2019 (COVID-19) 197:231 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 9 69 theme chain 1687:1691 arg1 fragment 1700:1707 the non-glycosylated heavy chain (NGHC) fragment 1660:1707 the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE) 1660:1717 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 69 theme chain 1687:1691 arg1 SDS-CGE 1710:1716 SDS-CGE 1710:1716 SDS-CGE 1710:1716 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 70 theme N-glycosylation 1911:1925 arg1 profiling 1927:1935 N-glycosylation profiling 1911:1935 N-glycosylation profiling 1911:1935 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 3 71 theme angiotensin-converting 636:657 arg1 receptor 668:675 the angiotensin-converting enzyme 2 receptor 632:675 the angiotensin-converting enzyme 2 receptor 632:675 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 3 72 theme Spike 521:525 arg1 protein 527:533 the Spike protein 517:533 the Spike protein expressed on the surface of the virus 517:571 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 1 73 theme worldwide 266:274 arg1 problem 258:264 a major public health problem 236:264 a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 236:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 1 73 theme worldwide 266:274 arg1 Disease 209:215 Coronavirus Disease 2019 197:220 Coronavirus Disease 2019 (COVID-19) 197:231 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 4 74 dep inhibit 760:766 arg1 represent 866:874 represent 866:874 represent a promising pharmacological strategy 866:911 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 4 74 dep inhibit 760:766 arg1 prevent 836:842 prevent 836:842 prevent SARS-CoV-2 infection 836:863 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 9 75 theme fragment 1700:1707 arg1 presence/absence 1640:1655 the presence/absence 1636:1655 the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE) 1636:1717 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 11 76 theme cytotoxicity 2336:2347 arg1 function 2365:2372 cytotoxicity (ADCC) effector function 2336:2372 cytotoxicity (ADCC) effector function 2336:2372 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 11 77 theme possible 2281:2288 arg1 existence 2290:2298 the possible existence 2277:2298 the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule 2277:2481 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 1 78 theme Coronavirus 197:207 arg1 problem 258:264 a major public health problem 236:264 a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 236:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 1 78 theme Coronavirus 197:207 arg1 Disease 209:215 Coronavirus Disease 2019 197:220 Coronavirus Disease 2019 (COVID-19) 197:231 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 1 78 theme Coronavirus 197:207 arg1 COVID-19 223:230 COVID-19 223:230 COVID-19 223:230 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 4 79 theme receptor 807:814 arg1 binding 816:822 angiotensin-converting enzyme 2 (ACE2) receptor binding 768:822 angiotensin-converting enzyme 2 (ACE2) receptor binding 768:822 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 10 80 theme negligible 1992:2001 arg1 amount 2003:2008 negligible amount 1992:2008 negligible amount of non-glycosylated heavy chain (NGHC) 1992:2047 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 10 80 theme negligible 1992:2001 arg1 NGHC 2043:2046 NGHC 2043:2046 NGHC 2043:2046 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 10 80 theme negligible 1992:2001 arg1 chain 2036:2040 non-glycosylated heavy chain 2013:2040 non-glycosylated heavy chain (NGHC) 2013:2047 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 0 81 theme Variant 135:141 arg1 Analysis 143:150 N-Glycosylation Variant Analysis 119:150 N-Glycosylation Variant Analysis 119:150 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 11 82 theme effector 2356:2363 arg1 function 2365:2372 cytotoxicity (ADCC) effector function 2336:2372 cytotoxicity (ADCC) effector function 2336:2372 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 4 83 contain having 713:718 arg1 antibodies 702:711 Neutralizing monoclonal antibodies 678:711 Neutralizing monoclonal antibodies having the RBD as a target 678:738 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 4 83 contain having 713:718 arg2 target 733:738 a target 731:738 a target 731:738 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 4 83 contain having 713:718 arg2 RBD 724:726 the RBD 720:726 the RBD 720:726 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 3 84 theme virus 567:571 arg1 surface 552:558 the surface 548:558 the surface of the virus 548:571 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 4 85 theme pharmacological 888:902 arg1 strategy 904:911 a promising pharmacological strategy 876:911 a promising pharmacological strategy 876:911 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 4 86 contain have 740:743 arg1 antibodies 702:711 Neutralizing monoclonal antibodies 678:711 Neutralizing monoclonal antibodies having the RBD as a target 678:738 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 4 86 contain have 740:743 arg2 ability 749:755 the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy 745:911 the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy 745:911 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 4 87 theme SARS-CoV-2 844:853 arg1 infection 855:863 SARS-CoV-2 infection 844:863 SARS-CoV-2 infection 844:863 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 8 88 theme therapeutic 1490:1500 arg1 antibodies 1502:1511 therapeutic antibodies 1490:1511 therapeutic antibodies 1490:1511 Various capillary gel electrophoresis methods are widely accepted in the biopharmaceutical industry for the characterization of therapeutic antibodies. 35350184 0 89 theme Anti-SARS-CoV-2 172:186 arg1 Product 188:194 an Anti-SARS-CoV-2 Product 169:194 an Anti-SARS-CoV-2 Product 169:194 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 0 89 theme Anti-SARS-CoV-2 172:186 arg1 Size 101:104 Size 101:104 Size 101:104 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 9 90 theme focusing 1749:1756 arg1 gel 1733:1735 a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel 1541:1735 a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing 1541:1756 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 5 91 theme first 934:938 arg1 antibody 975:982 the first anti-spike neutralizing monoclonal antibody 930:982 the first anti-spike neutralizing monoclonal antibody 930:982 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 5 91 theme first 934:938 arg1 Bamlanivimab 914:925 Bamlanivimab 914:925 Bamlanivimab 914:925 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 4 92 theme Neutralizing 678:689 arg1 antibodies 702:711 Neutralizing monoclonal antibodies 678:711 Neutralizing monoclonal antibodies having the RBD as a target 678:738 Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. 35350184 5 93 from FDA 1035:1037 arg1 authorization 1012:1024 an emergency use authorization 995:1024 an emergency use authorization from the FDA for COVID-19 treatment 995:1060 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 9 94 theme possible 1762:1769 arg1 heterogeneity 1803:1815 possible N-glycosylation mediated charge heterogeneity 1762:1815 possible N-glycosylation mediated charge heterogeneity determination 1762:1829 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 7 95 theme effector 1189:1196 arg1 function 1198:1205 The effector function 1185:1205 The effector function of antibody therapeutics 1185:1230 The effector function of antibody therapeutics is greatly affected by their N-linked carbohydrates at the conserved Fc region, possibly influenced by the manufacturing process. 35350184 9 96 theme capillary 1543:1551 arg1 electrophoresis 1557:1571 capillary gel electrophoresis 1543:1571 a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing 1541:1756 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 97 theme mediated 1787:1794 arg1 heterogeneity 1803:1815 possible N-glycosylation mediated charge heterogeneity 1762:1815 possible N-glycosylation mediated charge heterogeneity determination 1762:1829 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 11 98 theme antibody 2465:2472 arg1 molecule 2474:2481 this particular therapeutic antibody molecule 2437:2481 this particular therapeutic antibody molecule 2437:2481 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 10 99 theme acidic 2059:2064 arg1 variants 2073:2080 25% acidic charge variants 2055:2080 25% acidic charge variants 2055:2080 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 9 100 theme electrophoresis 1557:1571 arg1 gel 1733:1735 a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel 1541:1735 a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing 1541:1756 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 9 101 theme heterogeneity 1803:1815 arg1 determination 1817:1829 possible N-glycosylation mediated charge heterogeneity determination 1762:1829 possible N-glycosylation mediated charge heterogeneity determination 1762:1829 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 11 102 theme particular 2442:2451 arg1 molecule 2474:2481 this particular therapeutic antibody molecule 2437:2481 this particular therapeutic antibody molecule 2437:2481 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 5 103 theme neutralizing 951:962 arg1 antibody 975:982 the first anti-spike neutralizing monoclonal antibody 930:982 the first anti-spike neutralizing monoclonal antibody 930:982 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 5 103 theme neutralizing 951:962 arg1 Bamlanivimab 914:925 Bamlanivimab 914:925 Bamlanivimab 914:925 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 11 104 gly core-afucosylated 2190:2206 arg1 complex 2208:2214 approximately 8.2% core-afucosylated complex 2171:2214 approximately 8.2% core-afucosylated complex 2171:2214 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 11 105 theme dependent 2312:2320 arg1 cell 2322:2325 antibody dependent cell 2303:2325 antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule 2303:2481 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 2 106 theme Respiratory 431:441 arg1 Coronavirus 452:462 Severe Acute Respiratory Syndrome Coronavirus 2 418:464 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 418:477 The disease is caused by a betacoronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). 35350184 2 106 theme Respiratory 431:441 arg1 SARS-CoV-2 467:476 SARS-CoV-2 467:476 SARS-CoV-2 467:476 The disease is caused by a betacoronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). 35350184 0 107 theme Capillary 18:26 arg1 Workflow 54:61 a Capillary Gel Electrophoresis-Based Workflow 16:61 a Capillary Gel Electrophoresis-Based Workflow 16:61 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 1 108 theme % 285:285 arg1 hospitalization 287:301 5-10% hospitalization 281:301 5-10% hospitalization 281:301 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 9 109 theme size 1595:1598 arg1 analysis 1614:1621 size heterogeneity analysis 1595:1621 size heterogeneity analysis 1595:1621 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 11 110 link N-linked 2239:2246 arg1 oligosaccharides 2248:2263 galactosylated N-linked oligosaccharides 2224:2263 galactosylated N-linked oligosaccharides 2224:2263 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 7 111 theme conserved 1291:1299 arg1 region 1304:1309 the conserved Fc region 1287:1309 the conserved Fc region 1287:1309 The effector function of antibody therapeutics is greatly affected by their N-linked carbohydrates at the conserved Fc region, possibly influenced by the manufacturing process. 35350184 2 112 theme Severe 418:423 arg1 Coronavirus 452:462 Severe Acute Respiratory Syndrome Coronavirus 2 418:464 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 418:477 The disease is caused by a betacoronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). 35350184 2 112 theme Severe 418:423 arg1 SARS-CoV-2 467:476 SARS-CoV-2 467:476 SARS-CoV-2 467:476 The disease is caused by a betacoronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). 35350184 8 113 theme capillary 1370:1378 arg1 electrophoresis 1384:1398 capillary gel electrophoresis 1370:1398 Various capillary gel electrophoresis methods 1362:1406 Various capillary gel electrophoresis methods are widely accepted in the biopharmaceutical industry for the characterization of therapeutic antibodies. 35350184 0 114 theme Electrophoresis-Based 32:52 arg1 Workflow 54:61 a Capillary Gel Electrophoresis-Based Workflow 16:61 a Capillary Gel Electrophoresis-Based Workflow 16:61 Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product. 35350184 8 115 theme electrophoresis 1384:1398 arg1 methods 1400:1406 Various capillary gel electrophoresis methods 1362:1406 Various capillary gel electrophoresis methods 1362:1406 Various capillary gel electrophoresis methods are widely accepted in the biopharmaceutical industry for the characterization of therapeutic antibodies. 35350184 1 116 theme % 310:310 arg1 rates 329:333 5-10% hospitalization and 2-3% global mortality rates 281:333 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 281:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 11 117 theme cell 2322:2325 arg1 existence 2290:2298 the possible existence 2277:2298 the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule 2277:2481 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 5 118 theme use 1008:1010 arg1 authorization 1012:1024 an emergency use authorization 995:1024 an emergency use authorization from the FDA for COVID-19 treatment 995:1060 Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. 35350184 7 119 theme N-linked 1261:1268 arg1 carbohydrates 1270:1282 their N-linked carbohydrates 1255:1282 their N-linked carbohydrates 1255:1282 The effector function of antibody therapeutics is greatly affected by their N-linked carbohydrates at the conserved Fc region, possibly influenced by the manufacturing process. 35350184 3 120 theme receptor-binding 484:499 arg1 protein 527:533 the Spike protein 517:533 the Spike protein expressed on the surface of the virus 517:571 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 3 120 theme receptor-binding 484:499 arg1 RBD 509:511 RBD 509:511 RBD 509:511 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 3 120 theme receptor-binding 484:499 arg1 domain 501:506 The receptor-binding domain 480:506 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus 480:571 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 1 121 theme mortality 319:327 arg1 rates 329:333 5-10% hospitalization and 2-3% global mortality rates 281:333 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 281:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 6 122 theme neutralizing 1099:1110 arg1 mAb 1112:1114 a neutralizing mAb 1097:1114 a neutralizing mAb 1097:1114 Albeit, bamlanivimab is primarily a neutralizing mAb, some of its effector function related activity was also emphasized. 35350184 6 122 theme neutralizing 1099:1110 arg1 bamlanivimab 1071:1082 bamlanivimab 1071:1082 bamlanivimab 1071:1082 Albeit, bamlanivimab is primarily a neutralizing mAb, some of its effector function related activity was also emphasized. 35350184 11 123 theme considered 2403:2412 arg1 effect 2427:2432 the generally considered neutralizing effect 2389:2432 the generally considered neutralizing effect of this particular therapeutic antibody molecule 2389:2481 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 10 124 gly non-glycosylated 2013:2028 arg1 NGHC 2043:2046 NGHC 2043:2046 NGHC 2043:2046 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 10 124 gly non-glycosylated 2013:2028 arg1 chain 2036:2040 non-glycosylated heavy chain 2013:2040 non-glycosylated heavy chain (NGHC) 2013:2047 Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. 35350184 9 125 theme gel 1887:1889 arg1 electrophoresis 1891:1905 capillary gel electrophoresis 1877:1905 3) capillary gel electrophoresis for N-glycosylation profiling 1874:1935 In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. 35350184 3 126 theme enzyme 659:664 arg1 receptor 668:675 the angiotensin-converting enzyme 2 receptor 632:675 the angiotensin-converting enzyme 2 receptor 632:675 The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. 35350184 11 127 theme % 2222:2222 arg1 occurrence 2157:2166 the occurrence 2153:2166 the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides 2153:2263 Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule. 35350184 1 128 theme public 244:249 arg1 problem 258:264 a major public health problem 236:264 a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication 236:365 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 35350184 1 128 theme public 244:249 arg1 Disease 209:215 Coronavirus Disease 2019 197:220 Coronavirus Disease 2019 (COVID-19) 197:231 Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. 37086924 5 0 dep OBJECTIVE 759:767 arg1 sought 772:777 sought 772:777 sought to investigate the feasibility of activating TUSC3 expression to provide a potential therapeutic strategy for XMEN disease 772:900 OBJECTIVE We sought to investigate the feasibility of activating TUSC3 expression to provide a potential therapeutic strategy for XMEN disease. 37086924 7 1 theme KO 1182:1183 arg1 hepatocytes 1185:1195 MAGT1 KO hepatocytes 1176:1195 MAGT1 KO hepatocytes 1176:1195 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 1 2 from mutations 285:293 arg1 gene 334:337 the magnesium transporter 1 (MAGT1) gene 298:337 the magnesium transporter 1 (MAGT1) gene 298:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 4 3 theme high 718:721 arg1 sequence 723:730 high sequence 718:730 high sequence 718:730 Recent research shows that MAGT1 and tumor candidate suppressor 3 (TUSC3) share high sequence and functional similarity. 37086924 1 4 theme combined 226:233 arg1 deficiency 108:117 "X-linked MAGT1 deficiency 92:117 "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease 92:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 4 theme combined 226:233 arg1 CID 253:255 CID 253:255 CID 253:255 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 4 theme combined 226:233 arg1 immunodeficiency 235:250 a rare combined immunodeficiency 219:250 a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene 219:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 8 5 dep RESULTS 1198:1204 arg1 undetectable 1248:1259 undetectable 1248:1259 undetectable 1248:1259 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 37086924 9 6 theme CRISPR/Cas9-mediated 1366:1385 arg1 KO 1387:1388 CRISPR/Cas9-mediated KO 1366:1388 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line 1366:1418 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 1 7 theme X-linked 93:100 arg1 deficiency 108:117 "X-linked MAGT1 deficiency 92:117 "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease 92:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 7 theme X-linked 93:100 arg1 immunodeficiency 235:250 a rare combined immunodeficiency 219:250 a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene 219:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 7 8 theme MAGT1 1123:1127 arg1 lymphocytes 1160:1170 MAGT1 knock-out (KO)/patient-derived lymphocytes 1123:1170 MAGT1 knock-out (KO)/patient-derived lymphocytes 1123:1170 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 1 9 theme glycosylation 179:191 arg1 disease 208:214 N-linked glycosylation defect" (XMEN) disease 170:214 N-linked glycosylation defect" (XMEN) disease 170:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 2 10 theme Natural-Killer 509:522 arg1 D 540:540 member D 533:540 member D (NKG2D) 533:548 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 2 10 theme Natural-Killer 509:522 arg1 Group 524:528 Natural-Killer Group 2 509:530 Natural-Killer Group 2 509:530 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 9 11 theme NKL 1406:1408 arg1 line 1415:1418 the NKL cell line 1402:1418 the NKL cell line 1402:1418 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 11 12 theme immune 1779:1784 arg1 abnormalities 1796:1808 the immune and liver abnormalities 1775:1808 abnormalities 1796:1808 Combination treatment using these two drugs significantly upregulated TUSC3 expression and rescued the immune and liver abnormalities. 37086924 1 13 theme XMEN 202:205 arg1 disease 208:214 N-linked glycosylation defect" (XMEN) disease 170:214 N-linked glycosylation defect" (XMEN) disease 170:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 2 14 theme member 533:538 arg1 NKG2D 543:547 NKG2D 543:547 NKG2D 543:547 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 2 14 theme member 533:538 arg1 D 540:540 member D 533:540 member D (NKG2D) 533:548 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 2 14 theme member 533:538 arg1 Group 524:528 Natural-Killer Group 2 509:530 Natural-Killer Group 2 509:530 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 1 15 theme MAGT1 102:106 arg1 deficiency 108:117 "X-linked MAGT1 deficiency 92:117 "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease 92:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 15 theme MAGT1 102:106 arg1 immunodeficiency 235:250 a rare combined immunodeficiency 219:250 a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene 219:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 6 16 theme multiple 974:981 arg1 databases 983:991 multiple databases 974:991 multiple databases 974:991 METHODS The expression profiles of MAGT1 and TUSC3 were analyzed using multiple databases, RT‒PCR, and western blot. 37086924 1 17 dep BACKGROUND 81:90 arg1 deficiency 108:117 "X-linked MAGT1 deficiency 92:117 "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease 92:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 17 dep BACKGROUND 81:90 arg1 CID 253:255 CID 253:255 CID 253:255 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 17 dep BACKGROUND 81:90 arg1 immunodeficiency 235:250 a rare combined immunodeficiency 219:250 a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene 219:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 7 18 theme MAGT1 1176:1180 arg1 hepatocytes 1185:1195 MAGT1 KO hepatocytes 1176:1195 MAGT1 KO hepatocytes 1176:1195 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 9 19 theme XMEN 1460:1463 arg1 lymphocytes 1481:1491 XMEN patient-derived lymphocytes 1460:1491 XMEN patient-derived lymphocytes 1460:1491 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 1 20 theme magnesium 302:310 arg1 gene 334:337 the magnesium transporter 1 (MAGT1) gene 298:337 the magnesium transporter 1 (MAGT1) gene 298:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 12 21 theme therapeutic 1890:1900 arg1 strategy 1902:1909 an effective therapeutic strategy 1877:1909 an effective therapeutic strategy for XMEN disease 1877:1926 CONCLUSIONS Epigenetic activation of TUSC3 expression constitutes an effective therapeutic strategy for XMEN disease. 37086924 1 22 theme EBV 152:154 arg1 infection 156:164 EBV infection 152:164 EBV infection 152:164 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 6 23 theme TUSC3 948:952 arg1 profiles 926:933 The expression profiles 911:933 METHODS The expression profiles of MAGT1 and TUSC3 903:952 METHODS The expression profiles of MAGT1 and TUSC3 were analyzed using multiple databases, RT‒PCR, and western blot. 37086924 2 24 theme immune 484:489 arg1 receptors 491:499 key immune receptors 480:499 key immune receptors such as Natural-Killer Group 2, member D (NKG2D) 480:548 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 2 24 theme immune 484:489 arg1 Group 524:528 Natural-Killer Group 2 509:530 Natural-Killer Group 2 509:530 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 8 25 with consistent 1306:1315 arg1 tissues 1340:1346 the main diseased tissues 1322:1346 the main diseased tissues in XMEN patients 1322:1363 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 37086924 6 26 theme MAGT1 938:942 arg1 profiles 926:933 The expression profiles 911:933 METHODS The expression profiles of MAGT1 and TUSC3 903:952 METHODS The expression profiles of MAGT1 and TUSC3 were analyzed using multiple databases, RT‒PCR, and western blot. 37086924 1 27 link N-linked 170:177 arg1 disease 208:214 N-linked glycosylation defect" (XMEN) disease 170:214 N-linked glycosylation defect" (XMEN) disease 170:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 5 28 dep potential 854:862 arg1 therapeutic 864:874 therapeutic 864:874 therapeutic 864:874 OBJECTIVE We sought to investigate the feasibility of activating TUSC3 expression to provide a potential therapeutic strategy for XMEN disease. 37086924 1 29 theme MAGT1 327:331 arg1 gene 334:337 the magnesium transporter 1 (MAGT1) gene 298:337 the magnesium transporter 1 (MAGT1) gene 298:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 0 30 theme gene 35:38 arg1 activation 11:20 Epigenetic activation 0:20 Epigenetic activation of the TUSC3 gene as a potential therapy for XMEN disease. 0:79 Epigenetic activation of the TUSC3 gene as a potential therapy for XMEN disease. 37086924 4 31 theme candidate 681:689 arg1 suppressor 691:700 tumor candidate suppressor 3 675:702 tumor candidate suppressor 3 (TUSC3) 675:710 Recent research shows that MAGT1 and tumor candidate suppressor 3 (TUSC3) share high sequence and functional similarity. 37086924 4 31 theme candidate 681:689 arg1 TUSC3 705:709 TUSC3 705:709 TUSC3 705:709 Recent research shows that MAGT1 and tumor candidate suppressor 3 (TUSC3) share high sequence and functional similarity. 37086924 0 32 theme Epigenetic 0:9 arg1 activation 11:20 Epigenetic activation 0:20 Epigenetic activation of the TUSC3 gene as a potential therapy for XMEN disease. 0:79 Epigenetic activation of the TUSC3 gene as a potential therapy for XMEN disease. 37086924 9 33 theme TUSC3 1522:1526 arg1 expression 1508:1517 exogenous expression 1498:1517 exogenous expression of TUSC3 1498:1526 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 6 34 theme western 1006:1012 arg1 blot 1014:1017 western blot 1006:1017 western blot 1006:1017 METHODS The expression profiles of MAGT1 and TUSC3 were analyzed using multiple databases, RT‒PCR, and western blot. 37086924 10 35 theme epigenetic 1615:1624 arg1 decitabine 1633:1642 decitabine 1633:1642 decitabine 1633:1642 Using this in vitro model, we identified two epigenetic drugs, decitabine and panobinostat, by screening. 37086924 10 35 theme epigenetic 1615:1624 arg1 drugs 1626:1630 two epigenetic drugs 1611:1630 two epigenetic drugs 1611:1630 Using this in vitro model, we identified two epigenetic drugs, decitabine and panobinostat, by screening. 37086924 10 35 theme epigenetic 1615:1624 arg1 panobinostat 1648:1659 panobinostat 1648:1659 panobinostat 1648:1659 Using this in vitro model, we identified two epigenetic drugs, decitabine and panobinostat, by screening. 37086924 12 36 theme Epigenetic 1823:1832 arg1 activation 1834:1843 CONCLUSIONS Epigenetic activation 1811:1843 CONCLUSIONS Epigenetic activation of TUSC3 expression 1811:1863 CONCLUSIONS Epigenetic activation of TUSC3 expression constitutes an effective therapeutic strategy for XMEN disease. 37086924 9 37 from deficiencies 1540:1551 arg1 cells 1563:1567 KO NKL cells 1556:1567 KO NKL cells 1556:1567 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 0 38 theme potential 45:53 arg1 therapy 55:61 a potential therapy 43:61 a potential therapy for XMEN disease 43:78 Epigenetic activation of the TUSC3 gene as a potential therapy for XMEN disease. 37086924 8 39 theme diseased 1331:1338 arg1 tissues 1340:1346 the main diseased tissues 1322:1346 the main diseased tissues in XMEN patients 1322:1363 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 37086924 2 40 theme magnesium 365:373 arg1 transport 375:383 magnesium transport 365:383 magnesium transport 365:383 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 0 41 theme TUSC3 29:33 arg1 gene 35:38 the TUSC3 gene 25:38 the TUSC3 gene 25:38 Epigenetic activation of the TUSC3 gene as a potential therapy for XMEN disease. 37086924 3 42 theme system 579:584 arg1 abnormalities 586:598 immune system abnormalities 572:598 immune system abnormalities 572:598 These effects induce immune system abnormalities, chronic EBV infection and neoplasia. 37086924 7 43 theme TUSC3 1084:1088 arg1 expression 1090:1099 TUSC3 expression 1084:1099 TUSC3 expression 1084:1099 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 1 44 theme function 276:283 arg1 mutations 285:293 function mutations 276:293 function mutations in the magnesium transporter 1 (MAGT1) gene 276:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 9 45 theme NKL 1559:1561 arg1 cells 1563:1567 KO NKL cells 1556:1567 KO NKL cells 1556:1567 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 1 46 link X-linked 93:100 arg1 deficiency 108:117 "X-linked MAGT1 deficiency 92:117 "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease 92:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 46 link X-linked 93:100 arg1 immunodeficiency 235:250 a rare combined immunodeficiency 219:250 a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene 219:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 11 47 theme liver 1790:1794 arg1 abnormalities 1796:1808 the immune and liver abnormalities 1775:1808 abnormalities 1796:1808 Combination treatment using these two drugs significantly upregulated TUSC3 expression and rescued the immune and liver abnormalities. 37086924 7 48 theme panobinostat 1050:1061 arg1 effects 1024:1030 The effects 1020:1030 The effects of decitabine and panobinostat on the regulation of TUSC3 expression 1020:1099 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 3 49 theme EBV 609:611 arg1 infection 613:621 chronic EBV infection 601:621 chronic EBV infection 601:621 These effects induce immune system abnormalities, chronic EBV infection and neoplasia. 37086924 4 50 theme functional 736:745 arg1 similarity 747:756 functional similarity 736:756 functional similarity 736:756 Recent research shows that MAGT1 and tumor candidate suppressor 3 (TUSC3) share high sequence and functional similarity. 37086924 7 51 theme knock-out 1129:1137 arg1 lymphocytes 1160:1170 MAGT1 knock-out (KO)/patient-derived lymphocytes 1123:1170 MAGT1 knock-out (KO)/patient-derived lymphocytes 1123:1170 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 2 52 gly N-glycosylation 393:407 arg1 panel 414:418 a panel 412:418 a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D) 412:548 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 9 53 from KO 1387:1388 arg1 line 1415:1418 the NKL cell line 1402:1418 the NKL cell line 1402:1418 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 7 54 theme /patient-derived 1143:1158 arg1 lymphocytes 1160:1170 MAGT1 knock-out (KO)/patient-derived lymphocytes 1123:1170 MAGT1 knock-out (KO)/patient-derived lymphocytes 1123:1170 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 1 55 theme rare 221:224 arg1 deficiency 108:117 "X-linked MAGT1 deficiency 92:117 "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease 92:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 55 theme rare 221:224 arg1 CID 253:255 CID 253:255 CID 253:255 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 55 theme rare 221:224 arg1 immunodeficiency 235:250 a rare combined immunodeficiency 219:250 a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene 219:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 56 from loss 268:271 arg1 gene 334:337 the magnesium transporter 1 (MAGT1) gene 298:337 the magnesium transporter 1 (MAGT1) gene 298:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 7 57 theme decitabine 1035:1044 arg1 effects 1024:1030 The effects 1020:1030 The effects of decitabine and panobinostat on the regulation of TUSC3 expression 1020:1099 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 8 58 from tissues 1340:1346 arg1 patients 1356:1363 XMEN patients 1351:1363 XMEN patients 1351:1363 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 37086924 7 59 link /patient-derived 1143:1158 arg1 lymphocytes 1160:1170 MAGT1 knock-out (KO)/patient-derived lymphocytes 1123:1170 MAGT1 knock-out (KO)/patient-derived lymphocytes 1123:1170 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 1 60 theme N-linked 170:177 arg1 disease 208:214 N-linked glycosylation defect" (XMEN) disease 170:214 N-linked glycosylation defect" (XMEN) disease 170:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 61 theme defect 193:198 arg1 disease 208:214 N-linked glycosylation defect" (XMEN) disease 170:214 N-linked glycosylation defect" (XMEN) disease 170:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 6 62 theme expression 915:924 arg1 profiles 926:933 The expression profiles 911:933 METHODS The expression profiles of MAGT1 and TUSC3 903:952 METHODS The expression profiles of MAGT1 and TUSC3 were analyzed using multiple databases, RT‒PCR, and western blot. 37086924 9 63 theme lymphocytes 1481:1491 arg1 phenotypes 1446:1455 the phenotypes 1442:1455 the phenotypes of XMEN patient-derived lymphocytes 1442:1491 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 11 64 theme TUSC3 1746:1750 arg1 expression 1752:1761 TUSC3 expression 1746:1761 TUSC3 expression 1746:1761 Combination treatment using these two drugs significantly upregulated TUSC3 expression and rescued the immune and liver abnormalities. 37086924 5 65 theme TUSC3 824:828 arg1 expression 830:839 TUSC3 expression 824:839 TUSC3 expression 824:839 OBJECTIVE We sought to investigate the feasibility of activating TUSC3 expression to provide a potential therapeutic strategy for XMEN disease. 37086924 9 66 theme cell 1410:1413 arg1 line 1415:1418 the NKL cell line 1402:1418 the NKL cell line 1402:1418 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 2 67 theme receptors 491:499 arg1 expression 466:475 the expression 462:475 the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D) 462:548 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 6 68 dep METHODS 903:909 arg1 profiles 926:933 The expression profiles 911:933 METHODS The expression profiles of MAGT1 and TUSC3 903:952 METHODS The expression profiles of MAGT1 and TUSC3 were analyzed using multiple databases, RT‒PCR, and western blot. 37086924 5 69 theme potential 854:862 arg1 strategy 876:883 a potential therapeutic strategy 852:883 a potential therapeutic strategy for XMEN disease 852:900 OBJECTIVE We sought to investigate the feasibility of activating TUSC3 expression to provide a potential therapeutic strategy for XMEN disease. 37086924 9 70 theme MAGT1 1393:1397 arg1 KO 1387:1388 CRISPR/Cas9-mediated KO 1366:1388 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line 1366:1418 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 1 71 theme increased 124:132 arg1 susceptibility 134:147 increased susceptibility 124:147 increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease 124:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 11 72 theme Combination 1676:1686 arg1 treatment 1688:1696 Combination treatment 1676:1696 Combination treatment using these two drugs 1676:1718 Combination treatment using these two drugs significantly upregulated TUSC3 expression and rescued the immune and liver abnormalities. 37086924 0 73 theme XMEN 67:70 arg1 disease 72:78 XMEN disease 67:78 XMEN disease 67:78 Epigenetic activation of the TUSC3 gene as a potential therapy for XMEN disease. 37086924 9 74 theme patient-derived 1465:1479 arg1 lymphocytes 1481:1491 XMEN patient-derived lymphocytes 1460:1491 XMEN patient-derived lymphocytes 1460:1491 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 4 75 theme Recent 638:643 arg1 research 645:652 Recent research 638:652 Recent research 638:652 Recent research shows that MAGT1 and tumor candidate suppressor 3 (TUSC3) share high sequence and functional similarity. 37086924 7 76 theme KO 1140:1141 arg1 lymphocytes 1160:1170 MAGT1 knock-out (KO)/patient-derived lymphocytes 1123:1170 MAGT1 knock-out (KO)/patient-derived lymphocytes 1123:1170 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 1 77 theme transporter 312:322 arg1 gene 334:337 the magnesium transporter 1 (MAGT1) gene 298:337 the magnesium transporter 1 (MAGT1) gene 298:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 12 78 theme XMEN 1915:1918 arg1 disease 1920:1926 XMEN disease 1915:1926 XMEN disease 1915:1926 CONCLUSIONS Epigenetic activation of TUSC3 expression constitutes an effective therapeutic strategy for XMEN disease. 37086924 2 79 theme key 480:482 arg1 receptors 491:499 key immune receptors 480:499 key immune receptors such as Natural-Killer Group 2, member D (NKG2D) 480:548 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 2 79 theme key 480:482 arg1 Group 524:528 Natural-Killer Group 2 509:530 Natural-Killer Group 2 509:530 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 8 80 theme immune 1281:1286 arg1 system 1288:1293 the immune system 1277:1293 the immune system 1277:1293 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 37086924 1 81 from gene 334:337 arg1 loss 268:271 loss 268:271 loss of function mutations in the magnesium transporter 1 (MAGT1) gene 268:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 82 with deficiency 108:117 arg1 susceptibility 134:147 increased susceptibility 124:147 increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease 124:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 1 83 theme " 199:199 arg1 disease 208:214 N-linked glycosylation defect" (XMEN) disease 170:214 N-linked glycosylation defect" (XMEN) disease 170:214 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 9 84 theme exogenous 1498:1506 arg1 expression 1508:1517 exogenous expression 1498:1517 exogenous expression of TUSC3 1498:1526 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 2 85 theme MAGT1 340:344 arg1 deficiency 346:355 MAGT1 deficiency 340:355 MAGT1 deficiency 340:355 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 12 86 theme effective 1880:1888 arg1 strategy 1902:1909 an effective therapeutic strategy 1877:1909 an effective therapeutic strategy for XMEN disease 1877:1926 CONCLUSIONS Epigenetic activation of TUSC3 expression constitutes an effective therapeutic strategy for XMEN disease. 37086924 5 87 theme XMEN 889:892 arg1 disease 894:900 XMEN disease 889:900 XMEN disease 889:900 OBJECTIVE We sought to investigate the feasibility of activating TUSC3 expression to provide a potential therapeutic strategy for XMEN disease. 37086924 7 88 from effects 1024:1030 arg1 regulation 1070:1079 the regulation 1066:1079 the regulation of TUSC3 expression 1066:1099 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 4 89 theme tumor 675:679 arg1 suppressor 691:700 tumor candidate suppressor 3 675:702 tumor candidate suppressor 3 (TUSC3) 675:710 Recent research shows that MAGT1 and tumor candidate suppressor 3 (TUSC3) share high sequence and functional similarity. 37086924 4 89 theme tumor 675:679 arg1 TUSC3 705:709 TUSC3 705:709 TUSC3 705:709 Recent research shows that MAGT1 and tumor candidate suppressor 3 (TUSC3) share high sequence and functional similarity. 37086924 10 90 theme in 1581:1582 arg1 model 1590:1594 this in vitro model 1576:1594 this in vitro model 1576:1594 Using this in vitro model, we identified two epigenetic drugs, decitabine and panobinostat, by screening. 37086924 9 91 link patient-derived 1465:1479 arg1 lymphocytes 1481:1491 XMEN patient-derived lymphocytes 1460:1491 XMEN patient-derived lymphocytes 1460:1491 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 8 92 from undetectable 1248:1259 arg1 liver 1299:1303 liver 1299:1303 liver 1299:1303 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 37086924 8 92 from undetectable 1248:1259 arg1 system 1288:1293 the immune system 1277:1293 the immune system 1277:1293 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 37086924 7 93 theme expression 1090:1099 arg1 regulation 1070:1079 the regulation 1066:1079 the regulation of TUSC3 expression 1066:1099 The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knock-out (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. 37086924 12 94 theme TUSC3 1848:1852 arg1 expression 1854:1863 TUSC3 expression 1848:1863 TUSC3 expression 1848:1863 CONCLUSIONS Epigenetic activation of TUSC3 expression constitutes an effective therapeutic strategy for XMEN disease. 37086924 10 95 dep in 1581:1582 arg1 vitro 1584:1588 vitro 1584:1588 vitro 1584:1588 Using this in vitro model, we identified two epigenetic drugs, decitabine and panobinostat, by screening. 37086924 2 96 theme proteins 423:430 arg1 panel 414:418 a panel 412:418 a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D) 412:548 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 3 97 theme immune 572:577 arg1 abnormalities 586:598 immune system abnormalities 572:598 immune system abnormalities 572:598 These effects induce immune system abnormalities, chronic EBV infection and neoplasia. 37086924 8 98 theme main 1326:1329 arg1 tissues 1340:1346 the main diseased tissues 1322:1346 the main diseased tissues in XMEN patients 1322:1363 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 37086924 9 99 theme KO 1556:1557 arg1 cells 1563:1567 KO NKL cells 1556:1567 KO NKL cells 1556:1567 CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. 37086924 2 100 theme panel 414:418 arg1 transport 375:383 magnesium transport 365:383 magnesium transport 365:383 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 2 100 theme panel 414:418 arg1 N-glycosylation 393:407 the N-glycosylation 389:407 the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D) 389:548 MAGT1 deficiency impairs magnesium transport and the N-glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as Natural-Killer Group 2, member D (NKG2D). 37086924 12 101 theme expression 1854:1863 arg1 activation 1834:1843 CONCLUSIONS Epigenetic activation 1811:1843 CONCLUSIONS Epigenetic activation of TUSC3 expression 1811:1863 CONCLUSIONS Epigenetic activation of TUSC3 expression constitutes an effective therapeutic strategy for XMEN disease. 37086924 8 102 from liver 1299:1303 arg1 undetectable 1248:1259 undetectable 1248:1259 undetectable 1248:1259 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 37086924 1 103 theme mutations 285:293 arg1 loss 268:271 loss 268:271 loss of function mutations in the magnesium transporter 1 (MAGT1) gene 268:337 BACKGROUND "X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-linked glycosylation defect" (XMEN) disease is a rare combined immunodeficiency (CID) caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. 37086924 12 104 theme CONCLUSIONS 1811:1821 arg1 activation 1834:1843 CONCLUSIONS Epigenetic activation 1811:1843 CONCLUSIONS Epigenetic activation of TUSC3 expression 1811:1863 CONCLUSIONS Epigenetic activation of TUSC3 expression constitutes an effective therapeutic strategy for XMEN disease. 37086924 3 105 theme chronic 601:607 arg1 infection 613:621 chronic EBV infection 601:621 chronic EBV infection 601:621 These effects induce immune system abnormalities, chronic EBV infection and neoplasia. 37086924 8 106 theme XMEN 1351:1354 arg1 patients 1356:1363 XMEN patients 1351:1363 XMEN patients 1351:1363 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 37086924 8 107 from system 1288:1293 arg1 undetectable 1248:1259 undetectable 1248:1259 undetectable 1248:1259 RESULTS Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in XMEN patients. 36831567 0 0 theme Mass 87:90 arg1 Spectrometry 92:103 MALDI Mass Spectrometry 81:103 MALDI Mass Spectrometry 81:103 In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry. 36831567 1 1 theme N-acetylglucosamine 173:191 arg1 addition 161:168 the addition 157:168 the addition of N-acetylglucosamine (O-GlcNAc) 157:202 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 5 2 theme tumor 773:777 arg1 tissue 779:784 hepatic VX2 tumor tissue 761:784 hepatic VX2 tumor tissue 761:784 We use this strategy to monitor O-GlcNAc within hepatic VX2 tumor tissue. 36831567 0 3 theme MALDI 81:85 arg1 Spectrometry 92:103 MALDI Mass Spectrometry 81:103 MALDI Mass Spectrometry 81:103 In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry. 36831567 6 4 theme viable 840:845 arg1 tumor 847:851 both viable tumor and tumor margin regions 835:876 tumor 847:851 We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression. 36831567 2 5 theme modification 317:328 arg1 dynamics 289:296 perturbed dynamics 279:296 perturbed dynamics of O-GlcNAcylation modification 279:328 Processes driven by perturbed dynamics of O-GlcNAcylation modification have been implicated in cancer development. 36831567 5 6 theme hepatic 761:767 arg1 tissue 779:784 hepatic VX2 tumor tissue 761:784 hepatic VX2 tumor tissue 761:784 We use this strategy to monitor O-GlcNAc within hepatic VX2 tumor tissue. 36831567 4 7 theme imaging 512:518 arg1 use 481:483 the use 477:483 the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase 477:710 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 2 8 theme O-GlcNAcylation 301:315 arg1 modification 317:328 O-GlcNAcylation modification 301:328 O-GlcNAcylation modification 301:328 Processes driven by perturbed dynamics of O-GlcNAcylation modification have been implicated in cancer development. 36831567 1 9 gly O-glycosylation 125:139 arg1 proteins 144:151 proteins 144:151 proteins 144:151 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 4 10 theme spectrometry 499:510 arg1 MSI 521:523 MSI 521:523 MSI 521:523 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 4 10 theme spectrometry 499:510 arg1 imaging 512:518 MALDI-mass spectrometry imaging 488:518 MALDI-mass spectrometry imaging (MSI) 488:524 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 4 11 from location 543:550 arg1 sections 589:596 tissue sections 582:596 tissue sections 582:596 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 6 12 theme tumor 901:905 arg1 progression 907:917 tumor progression 901:917 tumor progression 901:917 We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression. 36831567 3 13 theme cancers 450:456 arg1 biomarker 432:440 a metabolic biomarker 420:440 a metabolic biomarker of many cancers 420:456 Variability in O-GlcNAcylation is emerging as a metabolic biomarker of many cancers. 36831567 5 14 theme VX2 769:771 arg1 tissue 779:784 hepatic VX2 tumor tissue 761:784 hepatic VX2 tumor tissue 761:784 We use this strategy to monitor O-GlcNAc within hepatic VX2 tumor tissue. 36831567 3 15 theme metabolic 422:430 arg1 biomarker 432:440 a metabolic biomarker 420:440 a metabolic biomarker of many cancers 420:456 Variability in O-GlcNAcylation is emerging as a metabolic biomarker of many cancers. 36831567 0 16 theme In 0:1 arg1 Imaging 8:14 In Situ Imaging 0:14 In Situ Imaging of O-Linked β-N-Acetylglucosamine 0:48 In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry. 36831567 4 17 theme tissue 582:587 arg1 sections 589:596 tissue sections 582:596 tissue sections 582:596 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 4 18 gly glycoproteins 670:682 arg1 glycoproteins 670:682 glycoproteins 670:682 glycoproteins using an O-GlcNAc hydrolase 670:710 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 6 19 theme increased 800:808 arg1 O-GlcNAc 810:817 increased O-GlcNAc 800:817 increased O-GlcNAc 800:817 We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression. 36831567 4 20 theme O-GlcNAc 693:700 arg1 hydrolase 702:710 an O-GlcNAc hydrolase 690:710 an O-GlcNAc hydrolase 690:710 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 1 21 theme Post-translational 106:123 arg1 regulator 209:217 a regulator 207:217 a regulator of many aspects of cellular physiology 207:256 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 1 21 theme Post-translational 106:123 arg1 O-glycosylation 125:139 Post-translational O-glycosylation 106:139 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) 106:202 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 4 22 theme enzymatic 646:654 arg1 hydrolysis 656:665 the enzymatic hydrolysis 642:665 the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase 642:710 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 0 23 theme β-N-Acetylglucosamine 28:48 arg1 Imaging 8:14 In Situ Imaging 0:14 In Situ Imaging of O-Linked β-N-Acetylglucosamine 0:48 In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry. 36831567 4 24 theme glycoproteins 670:682 arg1 hydrolysis 656:665 the enzymatic hydrolysis 642:665 the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase 642:710 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 1 25 theme many 222:225 arg1 aspects 227:233 many aspects 222:233 many aspects of cellular physiology 222:256 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 0 26 theme O-Linked 19:26 arg1 β-N-Acetylglucosamine 28:48 O-Linked β-N-Acetylglucosamine 19:48 O-Linked β-N-Acetylglucosamine 19:48 In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry. 36831567 4 27 theme MALDI-mass 488:497 arg1 MSI 521:523 MSI 521:523 MSI 521:523 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 4 27 theme MALDI-mass 488:497 arg1 imaging 512:518 MALDI-mass spectrometry imaging 488:518 MALDI-mass spectrometry imaging (MSI) 488:524 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 6 28 located found 822:826 arg1 tumor 847:851 both viable tumor and tumor margin regions 835:876 tumor 847:851 We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression. 36831567 6 28 located found 822:826 arg1 regions 870:876 both viable tumor and tumor margin regions 835:876 regions 870:876 We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression. 36831567 6 28 located found 822:826 arg2 O-GlcNAc 810:817 increased O-GlcNAc 800:817 increased O-GlcNAc 800:817 We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression. 36831567 1 29 theme aspects 227:233 arg1 regulator 209:217 a regulator 207:217 a regulator of many aspects of cellular physiology 207:256 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 1 29 theme aspects 227:233 arg1 O-glycosylation 125:139 Post-translational O-glycosylation 106:139 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) 106:202 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 0 30 theme On-Tissue 56:64 arg1 Hydrolysis 66:75 On-Tissue Hydrolysis 56:75 On-Tissue Hydrolysis 56:75 In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry. 36831567 3 31 theme many 445:448 arg1 cancers 450:456 many cancers 445:456 many cancers 445:456 Variability in O-GlcNAcylation is emerging as a metabolic biomarker of many cancers. 36831567 4 32 theme proteins 570:577 arg1 location 543:550 the location 539:550 the location of O-GlcNAcylated proteins in tissue sections 539:596 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 6 33 theme margin 863:868 arg1 regions 870:876 both viable tumor and tumor margin regions 835:876 regions 870:876 We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression. 36831567 1 34 theme proteins 144:151 arg1 regulator 209:217 a regulator 207:217 a regulator of many aspects of cellular physiology 207:256 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 1 34 theme proteins 144:151 arg1 O-glycosylation 125:139 Post-translational O-glycosylation 106:139 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) 106:202 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 4 35 theme O-GlcNAcylated 555:568 arg1 proteins 570:577 O-GlcNAcylated proteins 555:577 O-GlcNAcylated proteins 555:577 Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. 36831567 6 36 theme tumor 857:861 arg1 regions 870:876 both viable tumor and tumor margin regions 835:876 regions 870:876 We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression. 36831567 2 37 theme perturbed 279:287 arg1 dynamics 289:296 perturbed dynamics 279:296 perturbed dynamics of O-GlcNAcylation modification 279:328 Processes driven by perturbed dynamics of O-GlcNAcylation modification have been implicated in cancer development. 36831567 2 38 theme cancer 354:359 arg1 development 361:371 cancer development 354:371 cancer development 354:371 Processes driven by perturbed dynamics of O-GlcNAcylation modification have been implicated in cancer development. 36831567 1 39 theme cellular 238:245 arg1 physiology 247:256 cellular physiology 238:256 cellular physiology 238:256 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 3 40 from Variability 374:384 arg1 O-GlcNAcylation 389:403 O-GlcNAcylation 389:403 O-GlcNAcylation 389:403 Variability in O-GlcNAcylation is emerging as a metabolic biomarker of many cancers. 36831567 1 41 theme physiology 247:256 arg1 aspects 227:233 many aspects 222:233 many aspects of cellular physiology 222:256 Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. 36831567 0 42 dep In 0:1 arg1 Situ 3:6 Situ 3:6 Situ 3:6 In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry. 36824869 0 0 theme cell-to-cell 92:103 arg1 transfer 111:118 cell-to-cell viral transfer 92:118 cell-to-cell viral transfer 92:118 HIV-1 interaction with an O-glycan-specific bacterial lectin enhances virus infectivity and cell-to-cell viral transfer. 36824869 5 1 dep enhanced 829:836 arg1 whereas 882:888 whereas 882:888 whereas 882:888 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 4 2 theme HIV-1 738:742 arg1 Env 744:746 HIV-1 Env 738:746 HIV-1 Env 738:746 SLBR-N was demonstrated to capture HIV-1 virions, bind to O-glycans on HIV-1 Env, and augment CD4 binding to Env. 36824869 1 3 theme increased 172:180 arg1 risk 201:204 increased HIV-1 transmission risk 172:204 increased HIV-1 transmission risk 172:204 While bacterial dysbiosis has been associated with increased HIV-1 transmission risk, little is known about direct associations between HIV-1 and bacteria. 36824869 1 4 theme HIV-1 182:186 arg1 risk 201:204 increased HIV-1 transmission risk 172:204 increased HIV-1 transmission risk 172:204 While bacterial dysbiosis has been associated with increased HIV-1 transmission risk, little is known about direct associations between HIV-1 and bacteria. 36824869 3 5 theme Streptococcal 397:409 arg1 part 447:450 part 447:450 part of the fimbriae 447:466 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 3 5 theme Streptococcal 397:409 arg1 SLBR-N 430:435 The Streptococcal Siglec-like lectin SLBR-N 393:435 The Streptococcal Siglec-like lectin SLBR-N 393:435 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 0 6 theme viral 105:109 arg1 transfer 111:118 cell-to-cell viral transfer 92:118 cell-to-cell viral transfer 92:118 HIV-1 interaction with an O-glycan-specific bacterial lectin enhances virus infectivity and cell-to-cell viral transfer. 36824869 7 7 theme commensal 1183:1191 arg1 bacteria 1193:1200 commensal bacteria 1183:1200 commensal bacteria 1183:1200 Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa. 36824869 3 8 theme HIV-1 584:588 arg1 infectivity 590:600 HIV-1 infectivity 584:600 HIV-1 infectivity 584:600 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 7 9 theme O-glycan-binding 1153:1168 arg1 lectins 1170:1176 O-glycan-binding lectins 1153:1176 O-glycan-binding lectins from commensal bacteria 1153:1200 Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa. 36824869 5 10 theme N-glycan-binding 890:905 arg1 Msl 934:936 Msl 934:936 Msl 934:936 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 5 10 theme N-glycan-binding 890:905 arg1 FimH 925:928 FimH 925:928 FimH 925:928 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 5 10 theme N-glycan-binding 890:905 arg1 lectins 917:923 N-glycan-binding bacterial lectins 890:923 N-glycan-binding bacterial lectins FimH and Msl 890:936 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 2 11 theme HIV-1 298:302 arg1 interactions 304:315 HIV-1 interactions 298:315 HIV-1 interactions with bacteria 298:329 This study evaluated HIV-1 interactions with bacteria through glycan-binding lectins that affect virus infectivity. 36824869 5 12 theme bacterial 907:915 arg1 Msl 934:936 Msl 934:936 Msl 934:936 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 5 12 theme bacterial 907:915 arg1 FimH 925:928 FimH 925:928 FimH 925:928 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 5 12 theme bacterial 907:915 arg1 lectins 917:923 N-glycan-binding bacterial lectins 890:923 N-glycan-binding bacterial lectins FimH and Msl 890:936 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 1 13 theme transmission 188:199 arg1 risk 201:204 increased HIV-1 transmission risk 172:204 increased HIV-1 transmission risk 172:204 While bacterial dysbiosis has been associated with increased HIV-1 transmission risk, little is known about direct associations between HIV-1 and bacteria. 36824869 5 14 theme distinct 805:812 arg1 O-glycans 814:822 distinct O-glycans 805:822 distinct O-glycans 805:822 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 3 15 theme Siglec-like 411:421 arg1 part 447:450 part 447:450 part of the fimbriae 447:466 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 3 15 theme Siglec-like 411:421 arg1 SLBR-N 430:435 The Streptococcal Siglec-like lectin SLBR-N 393:435 The Streptococcal Siglec-like lectin SLBR-N 393:435 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 3 16 theme bacteria 482:489 arg1 surface 491:497 the bacteria surface 478:497 the bacteria surface 478:497 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 5 17 theme HIV-1 838:842 arg1 infectivity 844:854 HIV-1 infectivity 838:854 HIV-1 infectivity 838:854 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 3 18 theme fimbriae 459:466 arg1 part 447:450 part 447:450 part of the fimbriae 447:466 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 3 18 theme fimbriae 459:466 arg1 SLBR-N 430:435 The Streptococcal Siglec-like lectin SLBR-N 393:435 The Streptococcal Siglec-like lectin SLBR-N 393:435 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 0 19 theme HIV-1 0:4 arg1 interaction 6:16 HIV-1 interaction 0:16 HIV-1 interaction with an O-glycan-specific bacterial lectin 0:59 HIV-1 interaction with an O-glycan-specific bacterial lectin enhances virus infectivity and cell-to-cell viral transfer. 36824869 7 20 from exploitation 1137:1148 arg1 bacteria 1193:1200 commensal bacteria 1183:1200 commensal bacteria 1183:1200 Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa. 36824869 2 21 theme glycan-binding 339:352 arg1 lectins 354:360 glycan-binding lectins 339:360 glycan-binding lectins that affect virus infectivity 339:390 This study evaluated HIV-1 interactions with bacteria through glycan-binding lectins that affect virus infectivity. 36824869 3 22 theme lectin 423:428 arg1 part 447:450 part 447:450 part of the fimbriae 447:466 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 3 22 theme lectin 423:428 arg1 SLBR-N 430:435 The Streptococcal Siglec-like lectin SLBR-N 393:435 The Streptococcal Siglec-like lectin SLBR-N 393:435 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 7 23 theme lectins 1170:1176 arg1 exploitation 1137:1148 the exploitation 1133:1148 the exploitation of O-glycan-binding lectins from commensal bacteria 1133:1200 Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa. 36824869 4 24 theme CD4 761:763 arg1 binding 765:771 CD4 binding 761:771 CD4 binding to Env 761:778 SLBR-N was demonstrated to capture HIV-1 virions, bind to O-glycans on HIV-1 Env, and augment CD4 binding to Env. 36824869 6 25 theme plant 1012:1016 arg1 lectins 1018:1024 O-glycan-binding plant lectins 995:1024 O-glycan-binding plant lectins 995:1024 Enhancing effects were recapitulated with O-glycan-binding plant lectins. 36824869 5 26 theme lower 867:871 arg1 extents 873:879 lower extents 867:879 lower extents 867:879 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 0 27 theme bacterial 44:52 arg1 lectin 54:59 an O-glycan-specific bacterial lectin 23:59 an O-glycan-specific bacterial lectin 23:59 HIV-1 interaction with an O-glycan-specific bacterial lectin enhances virus infectivity and cell-to-cell viral transfer. 36824869 6 28 theme O-glycan-binding 995:1010 arg1 lectins 1018:1024 O-glycan-binding plant lectins 995:1024 O-glycan-binding plant lectins 995:1024 Enhancing effects were recapitulated with O-glycan-binding plant lectins. 36824869 7 29 theme HIV-1 1109:1113 arg1 infection 1115:1123 HIV-1 infection 1109:1123 HIV-1 infection 1109:1123 Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa. 36824869 3 30 theme infection 630:638 arg1 context 609:615 the context 605:615 the context of cell-free infection and cell-to-cell transfer 605:664 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 0 31 theme O-glycan-specific 26:42 arg1 lectin 54:59 an O-glycan-specific bacterial lectin 23:59 an O-glycan-specific bacterial lectin 23:59 HIV-1 interaction with an O-glycan-specific bacterial lectin enhances virus infectivity and cell-to-cell viral transfer. 36824869 5 32 dep lectins 917:923 arg1 Msl 934:936 Msl 934:936 Msl 934:936 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 5 32 dep lectins 917:923 arg1 FimH 925:928 FimH 925:928 FimH 925:928 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 5 32 dep lectins 917:923 arg1 lectins 917:923 N-glycan-binding bacterial lectins 890:923 N-glycan-binding bacterial lectins FimH and Msl 890:936 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 7 33 theme potential 1060:1068 arg1 contribution 1070:1081 the potential contribution 1056:1081 the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa 1056:1214 Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa. 36824869 1 34 theme direct 229:234 arg1 associations 236:247 direct associations 229:247 direct associations between HIV-1 and bacteria 229:274 While bacterial dysbiosis has been associated with increased HIV-1 transmission risk, little is known about direct associations between HIV-1 and bacteria. 36824869 5 35 theme Other 781:785 arg1 SLBRs 787:791 Other SLBRs 781:791 Other SLBRs recognizing distinct O-glycans 781:822 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 1 36 theme bacterial 127:135 arg1 dysbiosis 137:145 bacterial dysbiosis 127:145 bacterial dysbiosis 127:145 While bacterial dysbiosis has been associated with increased HIV-1 transmission risk, little is known about direct associations between HIV-1 and bacteria. 36824869 7 37 from bacteria 1193:1200 arg1 exploitation 1137:1148 the exploitation 1133:1148 the exploitation of O-glycan-binding lectins from commensal bacteria 1133:1200 Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa. 36824869 7 37 from bacteria 1193:1200 arg1 lectins 1170:1176 O-glycan-binding lectins 1153:1176 O-glycan-binding lectins from commensal bacteria 1153:1200 Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa. 36824869 3 38 link O-linked 529:536 arg1 glycans 538:544 α2,3 sialyated O-linked glycans 514:544 α2,3 sialyated O-linked glycans 514:544 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 3 39 theme cell-free 620:628 arg1 infection 630:638 cell-free infection 620:638 cell-free infection 620:638 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 0 40 with interaction 6:16 arg1 lectin 54:59 an O-glycan-specific bacterial lectin 23:59 an O-glycan-specific bacterial lectin 23:59 HIV-1 interaction with an O-glycan-specific bacterial lectin enhances virus infectivity and cell-to-cell viral transfer. 36824869 2 41 theme virus 374:378 arg1 infectivity 380:390 virus infectivity 374:390 virus infectivity 374:390 This study evaluated HIV-1 interactions with bacteria through glycan-binding lectins that affect virus infectivity. 36824869 3 42 theme sialyated 519:527 arg1 glycans 538:544 α2,3 sialyated O-linked glycans 514:544 α2,3 sialyated O-linked glycans 514:544 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 7 43 theme O-glycans 1086:1094 arg1 contribution 1070:1081 the potential contribution 1056:1081 the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa 1056:1214 Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa. 36824869 5 44 contain had 938:940 arg1 Msl 934:936 Msl 934:936 Msl 934:936 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 5 44 contain had 938:940 arg2 effect 945:950 no effect 942:950 no effect 942:950 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 5 44 contain had 938:940 arg1 FimH 925:928 FimH 925:928 FimH 925:928 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 5 44 contain had 938:940 arg1 lectins 917:923 N-glycan-binding bacterial lectins 890:923 N-glycan-binding bacterial lectins FimH and Msl 890:936 Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. 36824869 3 45 theme O-linked 529:536 arg1 glycans 538:544 α2,3 sialyated O-linked glycans 514:544 α2,3 sialyated O-linked glycans 514:544 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 3 46 theme cell-to-cell 644:655 arg1 transfer 657:664 cell-to-cell transfer 644:664 cell-to-cell transfer 644:664 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 4 47 theme HIV-1 702:706 arg1 virions 708:714 HIV-1 virions 702:714 HIV-1 virions 702:714 SLBR-N was demonstrated to capture HIV-1 virions, bind to O-glycans on HIV-1 Env, and augment CD4 binding to Env. 36824869 0 48 theme virus 70:74 arg1 infectivity 76:86 virus infectivity 70:86 virus infectivity 70:86 HIV-1 interaction with an O-glycan-specific bacterial lectin enhances virus infectivity and cell-to-cell viral transfer. 36824869 6 49 theme Enhancing 953:961 arg1 effects 963:969 Enhancing effects 953:969 Enhancing effects 953:969 Enhancing effects were recapitulated with O-glycan-binding plant lectins. 36824869 3 50 theme transfer 657:664 arg1 context 609:615 the context 605:615 the context of cell-free infection and cell-to-cell transfer 605:664 The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. 36824869 2 51 with interactions 304:315 arg1 bacteria 322:329 bacteria 322:329 bacteria 322:329 This study evaluated HIV-1 interactions with bacteria through glycan-binding lectins that affect virus infectivity. 36936781 1 0 theme canonical 157:165 arg1 TRPC6 175:179 TRPC6 175:179 TRPC6 175:179 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 1 0 theme canonical 157:165 arg1 channel 205:211 a non-voltage-gated channel 185:211 a non-voltage-gated channel that principally conducts calcium 185:245 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 1 0 theme canonical 157:165 arg1 type 167:170 Transient receptor potential canonical type 6 128:172 Transient receptor potential canonical type 6 (TRPC6) 128:180 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 7 1 theme combined 1042:1049 arg1 substitutions 1059:1071 combined alanine substitutions 1042:1071 combined alanine substitutions of the latter 1042:1085 Molecular modeling predicts interactions between Thr221-O-GlcNAc and Ser199, Glu200, and Glu246, and combined alanine substitutions of the latter similarly elevates resting NFAT activity. 36936781 7 2 theme resting 1106:1112 arg1 activity 1119:1126 resting NFAT activity 1106:1126 resting NFAT activity 1106:1126 Molecular modeling predicts interactions between Thr221-O-GlcNAc and Ser199, Glu200, and Glu246, and combined alanine substitutions of the latter similarly elevates resting NFAT activity. 36936781 8 3 theme TRPC6 1222:1226 arg1 conductance 1236:1246 normal TRPC6 channel conductance and NFAT activation 1215:1266 conductance 1236:1246 Thus, O-GlcNAcylated T221 and interactions with coordinating residues is required for normal TRPC6 channel conductance and NFAT activation. 36936781 0 4 theme potent 93:98 arg1 role 100:103 potent role 93:103 potent role 93:103 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation. 36936781 6 5 theme homologous 864:873 arg1 sites 858:862 sites 858:862 sites homologous in closely related TRPC3 and TRPC7 858:908 T→A mutations at sites homologous in closely related TRPC3 and TRPC7 also increases their activity. 36936781 7 6 theme latter 1080:1085 arg1 substitutions 1059:1071 combined alanine substitutions 1042:1071 combined alanine substitutions of the latter 1042:1085 Molecular modeling predicts interactions between Thr221-O-GlcNAc and Ser199, Glu200, and Glu246, and combined alanine substitutions of the latter similarly elevates resting NFAT activity. 36936781 3 7 theme β-N-acetyl 472:481 arg1 glucosamine 483:493 O-linked β-N-acetyl glucosamine 463:493 O-linked β-N-acetyl glucosamine (O-GlcNAcylation) 463:511 TRPC6 is post-translationally regulated, but a role for O-linked β-N-acetyl glucosamine (O-GlcNAcylation) as elevated by diabetes, is unknown. 36936781 3 7 theme β-N-acetyl 472:481 arg1 O-GlcNAcylation 496:510 O-GlcNAcylation 496:510 O-GlcNAcylation 496:510 TRPC6 is post-translationally regulated, but a role for O-linked β-N-acetyl glucosamine (O-GlcNAcylation) as elevated by diabetes, is unknown. 36936781 6 8 from sites 858:862 arg1 mutations 845:853 T→A mutations 841:853 T→A mutations at sites homologous in closely related TRPC3 and TRPC7 841:908 T→A mutations at sites homologous in closely related TRPC3 and TRPC7 also increases their activity. 36936781 5 9 theme associated 784:793 arg1 controller 739:748 a critical controller 728:748 a critical controller of resting TRPC6 conductance 728:777 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 9 theme associated 784:793 arg1 signaling 830:838 pro-hypertrophic signaling 813:838 pro-hypertrophic signaling 813:838 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 9 theme associated 784:793 arg1 activity 800:807 associated NFAT activity 784:807 associated NFAT activity 784:807 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 9 theme associated 784:793 arg1 T221 720:723 T221 720:723 T221 720:723 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 10 theme resting 753:759 arg1 conductance 767:777 resting TRPC6 conductance 753:777 resting TRPC6 conductance 753:777 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 8 11 theme channel 1228:1234 arg1 conductance 1236:1246 normal TRPC6 channel conductance and NFAT activation 1215:1266 conductance 1236:1246 Thus, O-GlcNAcylated T221 and interactions with coordinating residues is required for normal TRPC6 channel conductance and NFAT activation. 36936781 7 12 theme NFAT 1114:1117 arg1 activity 1119:1126 resting NFAT activity 1106:1126 resting NFAT activity 1106:1126 Molecular modeling predicts interactions between Thr221-O-GlcNAc and Ser199, Glu200, and Glu246, and combined alanine substitutions of the latter similarly elevates resting NFAT activity. 36936781 5 13 theme TRPC6 761:765 arg1 conductance 767:777 resting TRPC6 conductance 753:777 resting TRPC6 conductance 753:777 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 2 14 theme T-cells 391:397 arg1 NFAT 400:403 NFAT 400:403 NFAT 400:403 Elevated channel activation contributes to fibrosis, hypertrophy, and proteinuria, often coupled to stimulation of nuclear factor of activated T-cells (NFAT). 36936781 2 14 theme T-cells 391:397 arg1 factor 371:376 nuclear factor 363:376 nuclear factor of activated T-cells (NFAT) 363:404 Elevated channel activation contributes to fibrosis, hypertrophy, and proteinuria, often coupled to stimulation of nuclear factor of activated T-cells (NFAT). 36936781 0 15 theme receptor 10:17 arg1 O-GlcNAcylation 54:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation 0:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 0:85 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation. 36936781 6 16 theme T→A 841:843 arg1 mutations 845:853 T→A mutations 841:853 T→A mutations at sites homologous in closely related TRPC3 and TRPC7 841:908 T→A mutations at sites homologous in closely related TRPC3 and TRPC7 also increases their activity. 36936781 7 17 theme alanine 1051:1057 arg1 substitutions 1059:1071 combined alanine substitutions 1042:1071 combined alanine substitutions of the latter 1042:1085 Molecular modeling predicts interactions between Thr221-O-GlcNAc and Ser199, Glu200, and Glu246, and combined alanine substitutions of the latter similarly elevates resting NFAT activity. 36936781 8 18 with T221 1150:1153 arg1 residues 1190:1197 coordinating residues 1177:1197 coordinating residues 1177:1197 Thus, O-GlcNAcylated T221 and interactions with coordinating residues is required for normal TRPC6 channel conductance and NFAT activation. 36936781 2 19 theme activated 381:389 arg1 T-cells 391:397 activated T-cells 381:397 activated T-cells 381:397 Elevated channel activation contributes to fibrosis, hypertrophy, and proteinuria, often coupled to stimulation of nuclear factor of activated T-cells (NFAT). 36936781 0 20 theme Transient 0:8 arg1 O-GlcNAcylation 54:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation 0:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 0:85 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation. 36936781 4 21 theme LH1 675:677 arg1 domains 680:686 linker (LH1) domains 667:686 linker (LH1) domains 667:686 Here we show TRPC6 is constitutively O-GlcNAcylated at Ser14, Thr70, and Thr221 in the N-terminus ankryn-4 (AR4) and linker (LH1) domains. 36936781 4 22 from Thr221 623:628 arg1 O-GlcNAcylated 587:600 O-GlcNAcylated 587:600 O-GlcNAcylated 587:600 Here we show TRPC6 is constitutively O-GlcNAcylated at Ser14, Thr70, and Thr221 in the N-terminus ankryn-4 (AR4) and linker (LH1) domains. 36936781 0 23 theme canonical 29:37 arg1 O-GlcNAcylation 54:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation 0:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 0:85 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation. 36936781 3 24 dep role 454:457 arg1 elevated 516:523 elevated 516:523 elevated by diabetes 516:535 TRPC6 is post-translationally regulated, but a role for O-linked β-N-acetyl glucosamine (O-GlcNAcylation) as elevated by diabetes, is unknown. 36936781 0 25 theme potential 19:27 arg1 O-GlcNAcylation 54:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation 0:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 0:85 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation. 36936781 0 26 theme channel 108:114 arg1 regulation 116:125 channel regulation 108:125 channel regulation 108:125 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation. 36936781 0 27 from Threonine-221 73:85 arg1 O-GlcNAcylation 54:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation 0:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 0:85 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation. 36936781 1 28 theme receptor 138:145 arg1 TRPC6 175:179 TRPC6 175:179 TRPC6 175:179 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 1 28 theme receptor 138:145 arg1 channel 205:211 a non-voltage-gated channel 185:211 a non-voltage-gated channel that principally conducts calcium 185:245 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 1 28 theme receptor 138:145 arg1 type 167:170 Transient receptor potential canonical type 6 128:172 Transient receptor potential canonical type 6 (TRPC6) 128:180 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 5 29 theme NFAT 795:798 arg1 controller 739:748 a critical controller 728:748 a critical controller of resting TRPC6 conductance 728:777 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 29 theme NFAT 795:798 arg1 signaling 830:838 pro-hypertrophic signaling 813:838 pro-hypertrophic signaling 813:838 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 29 theme NFAT 795:798 arg1 activity 800:807 associated NFAT activity 784:807 associated NFAT activity 784:807 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 29 theme NFAT 795:798 arg1 T221 720:723 T221 720:723 T221 720:723 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 4 30 from Thr70 612:616 arg1 O-GlcNAcylated 587:600 O-GlcNAcylated 587:600 O-GlcNAcylated 587:600 Here we show TRPC6 is constitutively O-GlcNAcylated at Ser14, Thr70, and Thr221 in the N-terminus ankryn-4 (AR4) and linker (LH1) domains. 36936781 1 31 theme non-voltage-gated 187:203 arg1 type 167:170 Transient receptor potential canonical type 6 128:172 Transient receptor potential canonical type 6 (TRPC6) 128:180 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 1 31 theme non-voltage-gated 187:203 arg1 channel 205:211 a non-voltage-gated channel 185:211 a non-voltage-gated channel that principally conducts calcium 185:245 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 0 32 theme type 39:42 arg1 O-GlcNAcylation 54:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation 0:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 0:85 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation. 36936781 5 33 theme critical 730:737 arg1 controller 739:748 a critical controller 728:748 a critical controller of resting TRPC6 conductance 728:777 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 33 theme critical 730:737 arg1 signaling 830:838 pro-hypertrophic signaling 813:838 pro-hypertrophic signaling 813:838 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 33 theme critical 730:737 arg1 activity 800:807 associated NFAT activity 784:807 associated NFAT activity 784:807 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 33 theme critical 730:737 arg1 T221 720:723 T221 720:723 T221 720:723 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 34 theme conductance 767:777 arg1 controller 739:748 a critical controller 728:748 a critical controller of resting TRPC6 conductance 728:777 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 34 theme conductance 767:777 arg1 signaling 830:838 pro-hypertrophic signaling 813:838 pro-hypertrophic signaling 813:838 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 34 theme conductance 767:777 arg1 activity 800:807 associated NFAT activity 784:807 associated NFAT activity 784:807 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 34 theme conductance 767:777 arg1 T221 720:723 T221 720:723 T221 720:723 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 8 35 theme NFAT 1252:1255 arg1 activation 1257:1266 normal TRPC6 channel conductance and NFAT activation 1215:1266 activation 1257:1266 Thus, O-GlcNAcylated T221 and interactions with coordinating residues is required for normal TRPC6 channel conductance and NFAT activation. 36936781 0 36 theme TRPC6 47:51 arg1 O-GlcNAcylation 54:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation 0:68 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 0:85 Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation. 36936781 8 37 theme O-GlcNAcylated 1135:1148 arg1 T221 1150:1153 O-GlcNAcylated T221 1135:1153 O-GlcNAcylated T221 1135:1153 Thus, O-GlcNAcylated T221 and interactions with coordinating residues is required for normal TRPC6 channel conductance and NFAT activation. 36936781 3 38 link O-linked 463:470 arg1 glucosamine 483:493 O-linked β-N-acetyl glucosamine 463:493 O-linked β-N-acetyl glucosamine (O-GlcNAcylation) 463:511 TRPC6 is post-translationally regulated, but a role for O-linked β-N-acetyl glucosamine (O-GlcNAcylation) as elevated by diabetes, is unknown. 36936781 3 38 link O-linked 463:470 arg1 O-GlcNAcylation 496:510 O-GlcNAcylation 496:510 O-GlcNAcylation 496:510 TRPC6 is post-translationally regulated, but a role for O-linked β-N-acetyl glucosamine (O-GlcNAcylation) as elevated by diabetes, is unknown. 36936781 4 39 dep show 558:561 arg1 O-GlcNAcylated 587:600 O-GlcNAcylated 587:600 O-GlcNAcylated 587:600 Here we show TRPC6 is constitutively O-GlcNAcylated at Ser14, Thr70, and Thr221 in the N-terminus ankryn-4 (AR4) and linker (LH1) domains. 36936781 6 40 from TRPC3 894:898 arg1 homologous 864:873 homologous 864:873 homologous 864:873 T→A mutations at sites homologous in closely related TRPC3 and TRPC7 also increases their activity. 36936781 1 41 theme potential 147:155 arg1 TRPC6 175:179 TRPC6 175:179 TRPC6 175:179 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 1 41 theme potential 147:155 arg1 channel 205:211 a non-voltage-gated channel 185:211 a non-voltage-gated channel that principally conducts calcium 185:245 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 1 41 theme potential 147:155 arg1 type 167:170 Transient receptor potential canonical type 6 128:172 Transient receptor potential canonical type 6 (TRPC6) 128:180 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 4 42 theme linker 667:672 arg1 domains 680:686 linker (LH1) domains 667:686 linker (LH1) domains 667:686 Here we show TRPC6 is constitutively O-GlcNAcylated at Ser14, Thr70, and Thr221 in the N-terminus ankryn-4 (AR4) and linker (LH1) domains. 36936781 6 43 from homologous 864:873 arg1 TRPC7 904:908 TRPC7 904:908 TRPC7 904:908 T→A mutations at sites homologous in closely related TRPC3 and TRPC7 also increases their activity. 36936781 6 43 from homologous 864:873 arg1 TRPC3 894:898 TRPC3 894:898 TRPC3 894:898 T→A mutations at sites homologous in closely related TRPC3 and TRPC7 also increases their activity. 36936781 8 44 with interactions 1159:1170 arg1 residues 1190:1197 coordinating residues 1177:1197 coordinating residues 1177:1197 Thus, O-GlcNAcylated T221 and interactions with coordinating residues is required for normal TRPC6 channel conductance and NFAT activation. 36936781 3 45 theme O-linked 463:470 arg1 glucosamine 483:493 O-linked β-N-acetyl glucosamine 463:493 O-linked β-N-acetyl glucosamine (O-GlcNAcylation) 463:511 TRPC6 is post-translationally regulated, but a role for O-linked β-N-acetyl glucosamine (O-GlcNAcylation) as elevated by diabetes, is unknown. 36936781 3 45 theme O-linked 463:470 arg1 O-GlcNAcylation 496:510 O-GlcNAcylation 496:510 O-GlcNAcylation 496:510 TRPC6 is post-translationally regulated, but a role for O-linked β-N-acetyl glucosamine (O-GlcNAcylation) as elevated by diabetes, is unknown. 36936781 6 46 from TRPC7 904:908 arg1 homologous 864:873 homologous 864:873 homologous 864:873 T→A mutations at sites homologous in closely related TRPC3 and TRPC7 also increases their activity. 36936781 2 47 theme channel 257:263 arg1 activation 265:274 Elevated channel activation 248:274 Elevated channel activation 248:274 Elevated channel activation contributes to fibrosis, hypertrophy, and proteinuria, often coupled to stimulation of nuclear factor of activated T-cells (NFAT). 36936781 1 48 theme Transient 128:136 arg1 TRPC6 175:179 TRPC6 175:179 TRPC6 175:179 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 1 48 theme Transient 128:136 arg1 channel 205:211 a non-voltage-gated channel 185:211 a non-voltage-gated channel that principally conducts calcium 185:245 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 1 48 theme Transient 128:136 arg1 type 167:170 Transient receptor potential canonical type 6 128:172 Transient receptor potential canonical type 6 (TRPC6) 128:180 Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. 36936781 8 49 theme normal 1215:1220 arg1 conductance 1236:1246 normal TRPC6 channel conductance and NFAT activation 1215:1266 conductance 1236:1246 Thus, O-GlcNAcylated T221 and interactions with coordinating residues is required for normal TRPC6 channel conductance and NFAT activation. 36936781 2 50 theme Elevated 248:255 arg1 activation 265:274 Elevated channel activation 248:274 Elevated channel activation 248:274 Elevated channel activation contributes to fibrosis, hypertrophy, and proteinuria, often coupled to stimulation of nuclear factor of activated T-cells (NFAT). 36936781 2 51 theme factor 371:376 arg1 stimulation 348:358 stimulation 348:358 stimulation of nuclear factor of activated T-cells (NFAT) 348:404 Elevated channel activation contributes to fibrosis, hypertrophy, and proteinuria, often coupled to stimulation of nuclear factor of activated T-cells (NFAT). 36936781 5 52 theme pro-hypertrophic 813:828 arg1 controller 739:748 a critical controller 728:748 a critical controller of resting TRPC6 conductance 728:777 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 52 theme pro-hypertrophic 813:828 arg1 T221 720:723 T221 720:723 T221 720:723 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 52 theme pro-hypertrophic 813:828 arg1 activity 800:807 associated NFAT activity 784:807 associated NFAT activity 784:807 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 5 52 theme pro-hypertrophic 813:828 arg1 signaling 830:838 pro-hypertrophic signaling 813:838 pro-hypertrophic signaling 813:838 Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. 36936781 4 53 from Ser14 605:609 arg1 O-GlcNAcylated 587:600 O-GlcNAcylated 587:600 O-GlcNAcylated 587:600 Here we show TRPC6 is constitutively O-GlcNAcylated at Ser14, Thr70, and Thr221 in the N-terminus ankryn-4 (AR4) and linker (LH1) domains. 36936781 6 54 theme related 886:892 arg1 TRPC3 894:898 TRPC3 894:898 TRPC3 894:898 T→A mutations at sites homologous in closely related TRPC3 and TRPC7 also increases their activity. 36936781 8 55 theme coordinating 1177:1188 arg1 residues 1190:1197 coordinating residues 1177:1197 coordinating residues 1177:1197 Thus, O-GlcNAcylated T221 and interactions with coordinating residues is required for normal TRPC6 channel conductance and NFAT activation. 36936781 7 56 theme Molecular 941:949 arg1 modeling 951:958 Molecular modeling 941:958 Molecular modeling 941:958 Molecular modeling predicts interactions between Thr221-O-GlcNAc and Ser199, Glu200, and Glu246, and combined alanine substitutions of the latter similarly elevates resting NFAT activity. 36936781 2 57 theme nuclear 363:369 arg1 NFAT 400:403 NFAT 400:403 NFAT 400:403 Elevated channel activation contributes to fibrosis, hypertrophy, and proteinuria, often coupled to stimulation of nuclear factor of activated T-cells (NFAT). 36936781 2 57 theme nuclear 363:369 arg1 factor 371:376 nuclear factor 363:376 nuclear factor of activated T-cells (NFAT) 363:404 Elevated channel activation contributes to fibrosis, hypertrophy, and proteinuria, often coupled to stimulation of nuclear factor of activated T-cells (NFAT). 35138101 8 0 theme spatial 1001:1007 arg1 activation 1009:1018 spatial activation 1001:1018 spatial activation of OGT activity 1001:1034 Furthermore, we achieved spatial activation of OGT activity predominantly in the cytosol. 35138101 0 1 from Activation 15:24 arg1 Cells 63:67 Living Cells 56:67 Living Cells 56:67 Spatiotemporal Activation of Protein O-GlcNAcylation in Living Cells. 35138101 8 2 theme OGT 1023:1025 arg1 activity 1027:1034 OGT activity 1023:1034 OGT activity 1023:1034 Furthermore, we achieved spatial activation of OGT activity predominantly in the cytosol. 35138101 7 3 theme activation 899:908 arg1 strategy 910:917 this activation strategy 894:917 this activation strategy to control the morphological contraction of fibroblasts 894:973 We further apply this activation strategy to control the morphological contraction of fibroblasts. 35138101 6 4 theme glycoproteins 808:820 arg1 increase 766:773 the time-dependent increase 747:773 the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics 747:874 We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. 35138101 9 5 theme better 1207:1212 arg1 understanding 1214:1226 a better understanding 1205:1226 a better understanding of O-GlcNAc function 1205:1247 Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function. 35138101 9 6 theme chemical 1105:1112 arg1 tool 1114:1117 a valuable chemical tool 1094:1117 a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function 1094:1247 Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function. 35138101 9 7 theme spatiotemporal 1165:1178 arg1 precision 1180:1188 much needed spatiotemporal precision 1153:1188 much needed spatiotemporal precision 1153:1188 Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function. 35138101 6 8 theme profile 800:806 arg1 glycoproteins 808:820 cellular O-GlcNAc and profile glycoproteins 778:820 glycoproteins 808:820 We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. 35138101 1 9 theme O-linked 70:77 arg1 N-acetylglucosamine 79:97 O-linked N-acetylglucosamine 70:97 O-linked N-acetylglucosamine (O-GlcNAc) 70:108 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 1 9 theme O-linked 70:77 arg1 modification 133:144 a prevalent protein modification 113:144 a prevalent protein modification that plays fundamental roles in both cell physiology and pathology 113:211 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 1 9 theme O-linked 70:77 arg1 O-GlcNAc 100:107 O-GlcNAc 100:107 O-GlcNAc 100:107 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 9 10 theme cellular 1130:1137 arg1 O-GlcNAc 1139:1146 cellular O-GlcNAc 1130:1146 cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function 1130:1247 Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function. 35138101 3 11 from activity 360:367 arg1 cells 403:407 cells 403:407 cells 403:407 The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. 35138101 5 12 theme inactivated 610:620 arg1 form 622:625 a transiently inactivated form 596:625 a transiently inactivated form 596:625 This enables the expression of a transiently inactivated form of OGT, which can be rapidly reactivated by photo-decaging. 35138101 8 13 theme activity 1027:1034 arg1 activation 1009:1018 spatial activation 1001:1018 spatial activation of OGT activity 1001:1034 Furthermore, we achieved spatial activation of OGT activity predominantly in the cytosol. 35138101 1 14 link O-linked 70:77 arg1 N-acetylglucosamine 79:97 O-linked N-acetylglucosamine 70:97 O-linked N-acetylglucosamine (O-GlcNAc) 70:108 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 1 14 link O-linked 70:77 arg1 modification 133:144 a prevalent protein modification 113:144 a prevalent protein modification that plays fundamental roles in both cell physiology and pathology 113:211 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 1 14 link O-linked 70:77 arg1 O-GlcNAc 100:107 O-GlcNAc 100:107 O-GlcNAc 100:107 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 4 15 from cells 459:463 arg1 control 432:438 light control 426:438 light control of OGT activity in cells 426:463 Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. 35138101 6 16 theme O-GlcNAc 787:794 arg1 increase 766:773 the time-dependent increase 747:773 the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics 747:874 We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. 35138101 0 17 theme Spatiotemporal 0:13 arg1 Activation 15:24 Spatiotemporal Activation 0:24 Spatiotemporal Activation of Protein O-GlcNAcylation in Living Cells 0:67 Spatiotemporal Activation of Protein O-GlcNAcylation in Living Cells. 35138101 1 18 theme cell 183:186 arg1 physiology 188:197 cell physiology 183:197 cell physiology 183:197 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 6 19 theme cellular 778:785 arg1 O-GlcNAc 787:794 cellular O-GlcNAc and profile glycoproteins 778:820 O-GlcNAc 787:794 We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. 35138101 4 20 theme activity 447:454 arg1 control 432:438 light control 426:438 light control of OGT activity in cells 426:463 Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. 35138101 9 21 from aids 1197:1200 arg1 understanding 1214:1226 a better understanding 1205:1226 a better understanding of O-GlcNAc function 1205:1247 Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function. 35138101 3 22 theme spatiotemporal 374:387 arg1 resolution 389:398 spatiotemporal resolution 374:398 spatiotemporal resolution 374:398 The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. 35138101 4 23 theme encoded 538:544 arg1 lysine 557:562 a genetically encoded photocaged lysine 524:562 a genetically encoded photocaged lysine 524:562 Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. 35138101 4 24 from activity 447:454 arg1 cells 459:463 cells 459:463 cells 459:463 Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. 35138101 7 25 theme fibroblasts 963:973 arg1 contraction 948:958 the morphological contraction 930:958 the morphological contraction of fibroblasts 930:973 We further apply this activation strategy to control the morphological contraction of fibroblasts. 35138101 3 26 with activity 360:367 arg1 resolution 389:398 spatiotemporal resolution 374:398 spatiotemporal resolution 374:398 The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. 35138101 3 27 theme OGT 356:358 arg1 activity 360:367 OGT activity 356:367 OGT activity with spatiotemporal resolution in cells 356:407 The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. 35138101 9 28 with O-GlcNAc 1139:1146 arg1 precision 1180:1188 much needed spatiotemporal precision 1153:1188 much needed spatiotemporal precision 1153:1188 Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function. 35138101 9 29 theme function 1240:1247 arg1 understanding 1214:1226 a better understanding 1205:1226 a better understanding of O-GlcNAc function 1205:1247 Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function. 35138101 9 30 theme O-GlcNAc 1231:1238 arg1 function 1240:1247 O-GlcNAc function 1231:1247 O-GlcNAc function 1231:1247 Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function. 35138101 4 31 theme photocaged 546:555 arg1 lysine 557:562 a genetically encoded photocaged lysine 524:562 a genetically encoded photocaged lysine 524:562 Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. 35138101 4 32 from control 432:438 arg1 cells 459:463 cells 459:463 cells 459:463 Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. 35138101 4 33 theme light 426:430 arg1 control 432:438 light control 426:438 light control of OGT activity in cells 426:463 Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. 35138101 2 34 theme O-GlcNAc 246:253 arg1 OGT 268:270 OGT 268:270 OGT 268:270 O-GlcNAc is catalyzed solely by O-GlcNAc transferase (OGT). 35138101 2 34 theme O-GlcNAc 246:253 arg1 transferase 255:265 O-GlcNAc transferase 246:265 O-GlcNAc transferase (OGT) 246:271 O-GlcNAc is catalyzed solely by O-GlcNAc transferase (OGT). 35138101 9 35 theme needed 1158:1163 arg1 precision 1180:1188 much needed spatiotemporal precision 1153:1188 much needed spatiotemporal precision 1153:1188 Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function. 35138101 0 36 theme O-GlcNAcylation 37:51 arg1 Activation 15:24 Spatiotemporal Activation 0:24 Spatiotemporal Activation of Protein O-GlcNAcylation in Living Cells 0:67 Spatiotemporal Activation of Protein O-GlcNAcylation in Living Cells. 35138101 6 37 gly glycoproteins 808:820 arg1 glycoproteins 808:820 cellular O-GlcNAc and profile glycoproteins 778:820 glycoproteins 808:820 We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. 35138101 4 38 theme OGT 443:445 arg1 activity 447:454 OGT activity 443:454 OGT activity in cells 443:463 Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. 35138101 0 39 theme Protein 29:35 arg1 O-GlcNAcylation 37:51 Protein O-GlcNAcylation 29:51 Protein O-GlcNAcylation 29:51 Spatiotemporal Activation of Protein O-GlcNAcylation in Living Cells. 35138101 4 40 theme essential 494:502 arg1 residue 511:517 a catalytically essential lysine residue 478:517 a catalytically essential lysine residue 478:517 Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. 35138101 3 41 theme tools 339:343 arg1 lack 331:334 the lack 327:334 the lack of tools to control OGT activity with spatiotemporal resolution in cells 327:407 The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. 35138101 4 42 theme lysine 504:509 arg1 residue 511:517 a catalytically essential lysine residue 478:517 a catalytically essential lysine residue 478:517 Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. 35138101 3 43 theme function 304:311 arg1 study 278:282 The study 274:282 The study of protein O-GlcNAc function 274:311 The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. 35138101 1 44 theme prevalent 115:123 arg1 modification 133:144 a prevalent protein modification 113:144 a prevalent protein modification that plays fundamental roles in both cell physiology and pathology 113:211 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 1 44 theme prevalent 115:123 arg1 N-acetylglucosamine 79:97 O-linked N-acetylglucosamine 70:97 O-linked N-acetylglucosamine (O-GlcNAc) 70:108 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 0 45 theme Living 56:61 arg1 Cells 63:67 Living Cells 56:67 Living Cells 56:67 Spatiotemporal Activation of Protein O-GlcNAcylation in Living Cells. 35138101 5 46 theme form 622:625 arg1 expression 582:591 the expression 578:591 the expression of a transiently inactivated form of OGT, which can be rapidly reactivated by photo-decaging 578:684 This enables the expression of a transiently inactivated form of OGT, which can be rapidly reactivated by photo-decaging. 35138101 1 47 theme protein 125:131 arg1 modification 133:144 a prevalent protein modification 113:144 a prevalent protein modification that plays fundamental roles in both cell physiology and pathology 113:211 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 1 47 theme protein 125:131 arg1 N-acetylglucosamine 79:97 O-linked N-acetylglucosamine 70:97 O-linked N-acetylglucosamine (O-GlcNAc) 70:108 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 3 48 theme protein 287:293 arg1 function 304:311 protein O-GlcNAc function 287:311 protein O-GlcNAc function 287:311 The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. 35138101 9 49 theme valuable 1096:1103 arg1 tool 1114:1117 a valuable chemical tool 1094:1117 a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function 1094:1247 Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function. 35138101 3 50 theme O-GlcNAc 295:302 arg1 function 304:311 protein O-GlcNAc function 287:311 protein O-GlcNAc function 287:311 The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. 35138101 6 51 theme quantitative 852:863 arg1 proteomics 865:874 mass-spectrometry-based quantitative proteomics 828:874 mass-spectrometry-based quantitative proteomics 828:874 We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. 35138101 6 52 theme time-dependent 751:764 arg1 increase 766:773 the time-dependent increase 747:773 the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics 747:874 We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. 35138101 6 53 theme activity 724:731 arg1 activation 706:715 the activation 702:715 the activation of OGT activity 702:731 We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. 35138101 6 54 theme mass-spectrometry-based 828:850 arg1 proteomics 865:874 mass-spectrometry-based quantitative proteomics 828:874 mass-spectrometry-based quantitative proteomics 828:874 We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. 35138101 6 55 theme OGT 720:722 arg1 activity 724:731 OGT activity 720:731 OGT activity 720:731 We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. 35138101 7 56 theme morphological 934:946 arg1 contraction 948:958 the morphological contraction 930:958 the morphological contraction of fibroblasts 930:973 We further apply this activation strategy to control the morphological contraction of fibroblasts. 35138101 1 57 theme fundamental 157:167 arg1 roles 169:173 fundamental roles 157:173 fundamental roles 157:173 O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. 35138101 5 58 theme OGT 630:632 arg1 form 622:625 a transiently inactivated form 596:625 a transiently inactivated form 596:625 This enables the expression of a transiently inactivated form of OGT, which can be rapidly reactivated by photo-decaging. 34420053 3 0 theme family 367:372 arg1 S-glycosyltransferases 333:354 S-glycosyltransferases 333:354 S-glycosyltransferases of the GT2 family 333:372 S-glycosylation is an enzymatic process catalyzed by S-glycosyltransferases of the GT2 family. 34420053 4 1 theme ATCC 529:532 arg1 AQF52_3101 491:500 ORF AQF52_3101 487:500 ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439 487:538 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 0 2 theme glycosylation 93:105 arg1 S/O-HexNAc-transferase 45:66 S/O-HexNAc-transferase 45:66 S/O-HexNAc-transferase 45:66 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 0 2 theme glycosylation 93:105 arg1 evidence 72:79 evidence 72:79 evidence 72:79 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 4 3 theme acceptor 556:563 arg1 SvC 576:578 SvC 576:578 SvC 576:578 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 4 3 theme acceptor 556:563 arg1 substrate 565:573 its acceptor substrate 552:573 its acceptor substrate (SvC) 552:579 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 5 4 theme distinct 658:665 arg1 G 788:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 4 theme distinct 658:665 arg1 chemoselectivity 726:741 chemoselectivity 726:741 chemoselectivity 726:741 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 4 theme distinct 658:665 arg1 specificity 695:705 acceptor specificity 686:705 acceptor specificity 686:705 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 4 theme distinct 658:665 arg1 sequon 814:819 the minimum acceptor sequon 793:819 the minimum acceptor sequon of SvGT 793:827 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 4 theme distinct 658:665 arg1 regioselectivity 708:723 regioselectivity 708:723 regioselectivity 708:723 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 4 theme distinct 658:665 arg1 specificity 673:683 the distinct donor specificity 654:683 the distinct donor specificity 654:683 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 3 5 theme enzymatic 302:310 arg1 S-glycosylation 280:294 S-glycosylation 280:294 S-glycosylation 280:294 S-glycosylation is an enzymatic process catalyzed by S-glycosyltransferases of the GT2 family. 34420053 3 5 theme enzymatic 302:310 arg1 process 312:318 an enzymatic process 299:318 an enzymatic process catalyzed by S-glycosyltransferases of the GT2 family 299:372 S-glycosylation is an enzymatic process catalyzed by S-glycosyltransferases of the GT2 family. 34420053 5 6 theme Y 747:747 arg1 G 788:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 6 theme Y 747:747 arg1 chemoselectivity 726:741 chemoselectivity 726:741 chemoselectivity 726:741 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 6 theme Y 747:747 arg1 specificity 695:705 acceptor specificity 686:705 acceptor specificity 686:705 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 6 theme Y 747:747 arg1 sequon 814:819 the minimum acceptor sequon 793:819 the minimum acceptor sequon of SvGT 793:827 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 6 theme Y 747:747 arg1 regioselectivity 708:723 regioselectivity 708:723 regioselectivity 708:723 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 6 theme Y 747:747 arg1 specificity 673:683 the distinct donor specificity 654:683 the distinct donor specificity 654:683 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 7 theme donor 667:671 arg1 G 788:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 7 theme donor 667:671 arg1 chemoselectivity 726:741 chemoselectivity 726:741 chemoselectivity 726:741 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 7 theme donor 667:671 arg1 specificity 695:705 acceptor specificity 686:705 acceptor specificity 686:705 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 7 theme donor 667:671 arg1 sequon 814:819 the minimum acceptor sequon 793:819 the minimum acceptor sequon of SvGT 793:827 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 7 theme donor 667:671 arg1 regioselectivity 708:723 regioselectivity 708:723 regioselectivity 708:723 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 7 theme donor 667:671 arg1 specificity 673:683 the distinct donor specificity 654:683 the distinct donor specificity 654:683 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 4 8 theme inverting 435:443 arg1 S/O-HexNAc-transferase 445:466 an inverting S/O-HexNAc-transferase 432:466 an inverting S/O-HexNAc-transferase (SvGT) 432:473 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 4 8 theme inverting 435:443 arg1 SvGT 469:472 SvGT 469:472 SvGT 469:472 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 6 9 theme cellular 877:884 arg1 milieu 886:891 the cellular milieu 873:891 the cellular milieu 873:891 Although UDP-GlcNAc served as the donor in the cellular milieu, SvGT could also utilize UDP-Glc and UDP-GalNAc as donors in vitro. 34420053 6 10 from donor 864:868 arg1 milieu 886:891 the cellular milieu 873:891 the cellular milieu 873:891 Although UDP-GlcNAc served as the donor in the cellular milieu, SvGT could also utilize UDP-Glc and UDP-GalNAc as donors in vitro. 34420053 0 11 from evidence 72:79 arg1 Actinobacteria 110:123 Actinobacteria 110:123 Actinobacteria 110:123 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 5 12 theme in 628:629 arg1 assays 636:641 in vitro and in vivo assays 615:641 in vitro and in vivo assays 615:641 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 9 13 theme S/O-HexNAc-transferase 1445:1466 arg1 Actinobacteria 1403:1416 Actinobacteria 1403:1416 Actinobacteria 1403:1416 In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering. 34420053 9 13 theme S/O-HexNAc-transferase 1445:1466 arg1 application 1426:1436 the application 1422:1436 the application of its S/O-HexNAc-transferase in glycocin engineering 1422:1490 In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering. 34420053 4 14 theme venezuelae 518:527 arg1 ATCC 529:532 Streptomyces venezuelae ATCC 15439 505:538 Streptomyces venezuelae ATCC 15439 505:538 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 5 15 dep in 615:616 arg1 vitro 618:622 vitro 618:622 vitro 618:622 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 0 16 gly glycosylation 93:105 arg1 Actinobacteria 110:123 Actinobacteria 110:123 Actinobacteria 110:123 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 0 17 from S/O-HexNAc-transferase 45:66 arg1 Actinobacteria 110:123 Actinobacteria 110:123 Actinobacteria 110:123 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 8 18 theme specificities 1195:1207 arg1 understanding 1171:1183 an understanding 1168:1183 an understanding of enzyme specificities 1168:1207 With an understanding of enzyme specificities, we finally employed SvGT to generate two proof-of-concept neoglycocins against Listeria monocytogenes. 34420053 5 19 theme minimum 797:803 arg1 G 788:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 19 theme minimum 797:803 arg1 chemoselectivity 726:741 chemoselectivity 726:741 chemoselectivity 726:741 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 19 theme minimum 797:803 arg1 specificity 695:705 acceptor specificity 686:705 acceptor specificity 686:705 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 19 theme minimum 797:803 arg1 sequon 814:819 the minimum acceptor sequon 793:819 the minimum acceptor sequon of SvGT 793:827 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 19 theme minimum 797:803 arg1 regioselectivity 708:723 regioselectivity 708:723 regioselectivity 708:723 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 19 theme minimum 797:803 arg1 specificity 673:683 the distinct donor specificity 654:683 the distinct donor specificity 654:683 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 9 20 theme glycocin 1471:1478 arg1 engineering 1480:1490 glycocin engineering 1471:1490 glycocin engineering 1471:1490 In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering. 34420053 5 21 theme acceptor 686:693 arg1 G 788:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 21 theme acceptor 686:693 arg1 chemoselectivity 726:741 chemoselectivity 726:741 chemoselectivity 726:741 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 21 theme acceptor 686:693 arg1 specificity 695:705 acceptor specificity 686:705 acceptor specificity 686:705 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 21 theme acceptor 686:693 arg1 sequon 814:819 the minimum acceptor sequon 793:819 the minimum acceptor sequon of SvGT 793:827 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 21 theme acceptor 686:693 arg1 regioselectivity 708:723 regioselectivity 708:723 regioselectivity 708:723 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 21 theme acceptor 686:693 arg1 specificity 673:683 the distinct donor specificity 654:683 the distinct donor specificity 654:683 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 0 22 theme Biochemical 0:10 arg1 characterization 12:27 Biochemical characterization 0:27 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 0:124 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 4 23 theme ORF 487:489 arg1 AQF52_3101 491:500 ORF AQF52_3101 487:500 ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439 487:538 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 5 24 theme acceptor 805:812 arg1 G 788:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 24 theme acceptor 805:812 arg1 chemoselectivity 726:741 chemoselectivity 726:741 chemoselectivity 726:741 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 24 theme acceptor 805:812 arg1 specificity 695:705 acceptor specificity 686:705 acceptor specificity 686:705 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 24 theme acceptor 805:812 arg1 sequon 814:819 the minimum acceptor sequon 793:819 the minimum acceptor sequon of SvGT 793:827 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 24 theme acceptor 805:812 arg1 regioselectivity 708:723 regioselectivity 708:723 regioselectivity 708:723 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 24 theme acceptor 805:812 arg1 specificity 673:683 the distinct donor specificity 654:683 the distinct donor specificity 654:683 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 7 25 theme anti-O-GlcNAc 1035:1047 arg1 CTD110.6 1059:1066 CTD110.6 1059:1066 CTD110.6 1059:1066 Using mass spectrometry and western blotting, we provide evidence that an anti-O-GlcNAc antibody (CTD110.6) cross-reacts with S-GlcNAc and may be used to detect S-GlcNAcylated glycoconjugates directly. 34420053 7 25 theme anti-O-GlcNAc 1035:1047 arg1 antibody 1049:1056 an anti-O-GlcNAc antibody 1032:1056 an anti-O-GlcNAc antibody (CTD110.6) 1032:1067 Using mass spectrometry and western blotting, we provide evidence that an anti-O-GlcNAc antibody (CTD110.6) cross-reacts with S-GlcNAc and may be used to detect S-GlcNAcylated glycoconjugates directly. 34420053 5 26 theme in 615:616 arg1 assays 636:641 in vitro and in vivo assays 615:641 in vitro and in vivo assays 615:641 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 1 27 theme Antimicrobial 126:138 arg1 glycocins 199:207 glycocins 199:207 glycocins 199:207 Antimicrobial peptides harboring S- and or O-linked glycans are known as glycocins. 34420053 1 27 theme Antimicrobial 126:138 arg1 peptides 140:147 Antimicrobial peptides 126:147 Antimicrobial peptides harboring S- and or O-linked glycans 126:184 Antimicrobial peptides harboring S- and or O-linked glycans are known as glycocins. 34420053 9 28 from S/O-HexNAc-transferase 1445:1466 arg1 engineering 1480:1490 glycocin engineering 1471:1490 glycocin engineering 1471:1490 In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering. 34420053 9 29 from application 1426:1436 arg1 engineering 1480:1490 glycocin engineering 1471:1490 glycocin engineering 1471:1490 In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering. 34420053 5 30 theme SvGT 824:827 arg1 G 788:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G 747:788 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 30 theme SvGT 824:827 arg1 chemoselectivity 726:741 chemoselectivity 726:741 chemoselectivity 726:741 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 30 theme SvGT 824:827 arg1 specificity 695:705 acceptor specificity 686:705 acceptor specificity 686:705 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 30 theme SvGT 824:827 arg1 sequon 814:819 the minimum acceptor sequon 793:819 the minimum acceptor sequon of SvGT 793:827 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 30 theme SvGT 824:827 arg1 regioselectivity 708:723 regioselectivity 708:723 regioselectivity 708:723 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 5 30 theme SvGT 824:827 arg1 specificity 673:683 the distinct donor specificity 654:683 the distinct donor specificity 654:683 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 0 31 theme S/O-HexNAc-transferase 45:66 arg1 characterization 12:27 Biochemical characterization 0:27 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 0:124 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 9 32 theme first 1352:1356 arg1 evidence 1371:1378 the first experimental evidence 1348:1378 the first experimental evidence for S-glycosylation 1348:1398 In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering. 34420053 1 33 link O-linked 169:176 arg1 glycans 178:184 S- and or O-linked glycans 159:184 S- and or O-linked glycans 159:184 Antimicrobial peptides harboring S- and or O-linked glycans are known as glycocins. 34420053 0 34 from glycosylation 93:105 arg1 Actinobacteria 110:123 Actinobacteria 110:123 Actinobacteria 110:123 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 0 35 theme inverting 35:43 arg1 S/O-HexNAc-transferase 45:66 S/O-HexNAc-transferase 45:66 S/O-HexNAc-transferase 45:66 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 9 36 theme experimental 1358:1369 arg1 evidence 1371:1378 the first experimental evidence 1348:1378 the first experimental evidence for S-glycosylation 1348:1398 In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering. 34420053 8 37 theme enzyme 1188:1193 arg1 specificities 1195:1207 enzyme specificities 1188:1207 enzyme specificities 1188:1207 With an understanding of enzyme specificities, we finally employed SvGT to generate two proof-of-concept neoglycocins against Listeria monocytogenes. 34420053 4 38 theme Streptomyces 505:516 arg1 ATCC 529:532 Streptomyces venezuelae ATCC 15439 505:538 Streptomyces venezuelae ATCC 15439 505:538 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 7 39 theme S-GlcNAcylated 1122:1135 arg1 glycoconjugates 1137:1151 S-GlcNAcylated glycoconjugates 1122:1151 S-GlcNAcylated glycoconjugates 1122:1151 Using mass spectrometry and western blotting, we provide evidence that an anti-O-GlcNAc antibody (CTD110.6) cross-reacts with S-GlcNAc and may be used to detect S-GlcNAcylated glycoconjugates directly. 34420053 4 40 theme expression 396:405 arg1 system 407:412 a heterologous expression system 381:412 a heterologous expression system 381:412 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 8 41 theme proof-of-concept 1251:1266 arg1 neoglycocins 1268:1279 two proof-of-concept neoglycocins 1247:1279 two proof-of-concept neoglycocins against Listeria monocytogenes 1247:1310 With an understanding of enzyme specificities, we finally employed SvGT to generate two proof-of-concept neoglycocins against Listeria monocytogenes. 34420053 0 42 theme evidence 72:79 arg1 characterization 12:27 Biochemical characterization 0:27 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 0:124 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 7 43 used used 1107:1110 arg2 antibody 1049:1056 an anti-O-GlcNAc antibody 1032:1056 an anti-O-GlcNAc antibody (CTD110.6) 1032:1067 Using mass spectrometry and western blotting, we provide evidence that an anti-O-GlcNAc antibody (CTD110.6) cross-reacts with S-GlcNAc and may be used to detect S-GlcNAcylated glycoconjugates directly. 34420053 7 43 used used 1107:1110 arg2 CTD110.6 1059:1066 CTD110.6 1059:1066 CTD110.6 1059:1066 Using mass spectrometry and western blotting, we provide evidence that an anti-O-GlcNAc antibody (CTD110.6) cross-reacts with S-GlcNAc and may be used to detect S-GlcNAcylated glycoconjugates directly. 34420053 4 44 theme heterologous 383:394 arg1 system 407:412 a heterologous expression system 381:412 a heterologous expression system 381:412 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 8 45 theme Listeria 1289:1296 arg1 monocytogenes 1298:1310 Listeria monocytogenes 1289:1310 Listeria monocytogenes 1289:1310 With an understanding of enzyme specificities, we finally employed SvGT to generate two proof-of-concept neoglycocins against Listeria monocytogenes. 34420053 3 46 theme GT2 363:365 arg1 family 367:372 the GT2 family 359:372 the GT2 family 359:372 S-glycosylation is an enzymatic process catalyzed by S-glycosyltransferases of the GT2 family. 34420053 0 47 link S-linked 84:91 arg1 glycosylation 93:105 S-linked glycosylation 84:105 S-linked glycosylation in Actinobacteria 84:123 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 1 48 theme S- 159:160 arg1 glycans 178:184 S- and or O-linked glycans 159:184 S- and or O-linked glycans 159:184 Antimicrobial peptides harboring S- and or O-linked glycans are known as glycocins. 34420053 5 49 dep in 628:629 arg1 vivo 631:634 vivo 631:634 vivo 631:634 Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. 34420053 4 50 dep along 541:545 arg1 with 547:550 with 547:550 with 547:550 Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. 34420053 9 51 from Actinobacteria 1403:1416 arg1 engineering 1480:1490 glycocin engineering 1471:1490 glycocin engineering 1471:1490 In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering. 34420053 7 52 theme western 989:995 arg1 blotting 997:1004 western blotting 989:1004 western blotting 989:1004 Using mass spectrometry and western blotting, we provide evidence that an anti-O-GlcNAc antibody (CTD110.6) cross-reacts with S-GlcNAc and may be used to detect S-GlcNAcylated glycoconjugates directly. 34420053 9 53 from engineering 1480:1490 arg1 Actinobacteria 1403:1416 Actinobacteria 1403:1416 Actinobacteria 1403:1416 In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering. 34420053 9 53 from engineering 1480:1490 arg1 application 1426:1436 the application 1422:1436 the application of its S/O-HexNAc-transferase in glycocin engineering 1422:1490 In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering. 34420053 1 54 theme or 166:167 arg1 glycans 178:184 S- and or O-linked glycans 159:184 S- and or O-linked glycans 159:184 Antimicrobial peptides harboring S- and or O-linked glycans are known as glycocins. 34420053 0 55 theme S-linked 84:91 arg1 glycosylation 93:105 S-linked glycosylation 84:105 S-linked glycosylation in Actinobacteria 84:123 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 0 56 from Actinobacteria 110:123 arg1 S/O-HexNAc-transferase 45:66 S/O-HexNAc-transferase 45:66 S/O-HexNAc-transferase 45:66 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 0 56 from Actinobacteria 110:123 arg1 evidence 72:79 evidence 72:79 evidence 72:79 Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria. 34420053 7 57 theme mass 967:970 arg1 spectrometry 972:983 mass spectrometry 967:983 mass spectrometry 967:983 Using mass spectrometry and western blotting, we provide evidence that an anti-O-GlcNAc antibody (CTD110.6) cross-reacts with S-GlcNAc and may be used to detect S-GlcNAcylated glycoconjugates directly. 34420053 1 58 theme O-linked 169:176 arg1 glycans 178:184 S- and or O-linked glycans 159:184 S- and or O-linked glycans 159:184 Antimicrobial peptides harboring S- and or O-linked glycans are known as glycocins. 36720878 7 0 theme carbon 1476:1481 arg1 sinking 1483:1489 carbon sinking 1476:1489 carbon sinking 1476:1489 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 0 1 theme Viral 0:4 arg1 infection 6:14 Viral infection 0:14 Viral infection 0:14 Viral infection switches the balance between bacterial and eukaryotic recyclers of organic matter during coccolithophore blooms. 36720878 4 2 theme biogeochemical 672:685 arg1 landscape 687:695 the evolving biogeochemical landscape 659:695 the evolving biogeochemical landscape 659:695 Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. 36720878 8 3 from recyclers 1603:1611 arg1 blooms 1662:1667 large-scale coccolithophore blooms 1634:1667 large-scale coccolithophore blooms 1634:1667 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 1 4 theme central 193:199 arg1 roles 201:205 central roles 193:205 central roles in microbial ecology and global elemental cycling 193:255 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 7 5 from increase 1319:1326 arg1 rates 1340:1344 per-cell rates 1331:1344 per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean 1331:1509 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 7 6 theme carbon 1442:1447 arg1 form 1385:1388 the form 1381:1388 the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking 1381:1489 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 4 7 theme bloom-associated 614:629 arg1 microbiome 631:640 a bloom-associated microbiome 612:640 a bloom-associated microbiome 612:640 Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. 36720878 7 8 theme particulate 1420:1430 arg1 carbon 1442:1447 particulate inorganic carbon 1420:1447 particulate inorganic carbon 1420:1447 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 8 9 from impact 1537:1542 arg1 fate 1570:1573 the fate 1566:1573 the fate of carbon 1566:1583 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 7 10 theme polysaccharides 1400:1414 arg1 form 1385:1388 the form 1381:1388 the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking 1381:1489 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 4 11 theme large-scale 714:724 arg1 experiment 735:744 a large-scale mesocosm experiment 712:744 a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms 712:798 Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. 36720878 1 12 from roles 201:205 arg1 cycling 249:255 global elemental cycling 232:255 global elemental cycling 232:255 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 1 12 from roles 201:205 arg1 ecology 220:226 microbial ecology 210:226 microbial ecology 210:226 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 1 13 theme Algal 129:133 arg1 blooms 135:140 Algal blooms 129:140 Algal blooms 129:140 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 1 13 theme Algal 129:133 arg1 hotspots 146:153 hotspots 146:153 hotspots of marine primary production 146:182 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 0 14 theme eukaryotic 59:68 arg1 recyclers 70:78 bacterial and eukaryotic recyclers 45:78 bacterial and eukaryotic recyclers of organic matter 45:96 Viral infection switches the balance between bacterial and eukaryotic recyclers of organic matter during coccolithophore blooms. 36720878 1 15 theme primary 165:171 arg1 production 173:182 marine primary production 158:182 marine primary production 158:182 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 4 16 theme coccolithophore 777:791 arg1 blooms 793:798 seven induced coccolithophore blooms 763:798 seven induced coccolithophore blooms 763:798 Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. 36720878 0 17 theme matter 91:96 arg1 recyclers 70:78 bacterial and eukaryotic recyclers 45:78 bacterial and eukaryotic recyclers of organic matter 45:96 Viral infection switches the balance between bacterial and eukaryotic recyclers of organic matter during coccolithophore blooms. 36720878 5 18 theme eukaryotic 989:998 arg1 assemblages 1000:1010 free-living bacterial and eukaryotic assemblages 963:1010 free-living bacterial and eukaryotic assemblages 963:1010 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 8 19 theme infection 1553:1561 arg1 impact 1537:1542 the impact 1533:1542 the impact of viral infection on the fate of carbon 1533:1583 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 0 20 theme coccolithophore 105:119 arg1 blooms 121:126 coccolithophore blooms 105:126 coccolithophore blooms 105:126 Viral infection switches the balance between bacterial and eukaryotic recyclers of organic matter during coccolithophore blooms. 36720878 2 21 theme bacterial 374:382 arg1 production 392:401 bacterial biomass production 374:401 bacterial biomass production 374:401 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 2 21 theme bacterial 374:382 arg1 levels 366:371 either higher trophic levels 344:371 either higher trophic levels 344:371 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 7 22 theme viral 1223:1227 arg1 infection 1229:1237 active viral infection 1216:1237 active viral infection 1216:1237 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 7 23 theme carbon 1363:1368 arg1 release 1370:1376 extracellular carbon release 1349:1376 extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean 1349:1509 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 5 24 theme infection 844:852 arg1 degrees 827:833 different degrees 817:833 different degrees of viral infection 817:852 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 5 25 theme bacterial 975:983 arg1 assemblages 1000:1010 free-living bacterial and eukaryotic assemblages 963:1010 free-living bacterial and eukaryotic assemblages 963:1010 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 3 26 theme bloom 443:447 arg1 termination 449:459 bloom termination 443:459 bloom termination 443:459 Viral infection can lead to bloom termination, but its impact on the fate of carbon remains largely unquantified. 36720878 5 27 theme high 875:878 arg1 levels 880:885 only high levels 870:885 only high levels of viral infection 870:904 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 6 28 theme eukaryotic 1063:1072 arg1 thraustochytrids 1088:1103 thraustochytrids 1088:1103 thraustochytrids 1088:1103 Intriguingly, upon viral infection the biomass of eukaryotic heterotrophs (thraustochytrids) rivals that of bacteria as potential recyclers of organic matter. 36720878 6 28 theme eukaryotic 1063:1072 arg1 heterotrophs 1074:1085 eukaryotic heterotrophs 1063:1085 eukaryotic heterotrophs (thraustochytrids) 1063:1104 Intriguingly, upon viral infection the biomass of eukaryotic heterotrophs (thraustochytrids) rivals that of bacteria as potential recyclers of organic matter. 36720878 5 29 theme different 817:825 arg1 degrees 827:833 different degrees 817:833 different degrees of viral infection 817:852 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 7 30 from rates 1340:1344 arg1 form 1385:1388 the form 1381:1388 the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking 1381:1489 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 6 31 theme matter 1164:1169 arg1 recyclers 1143:1151 potential recyclers 1133:1151 potential recyclers of organic matter 1133:1169 Intriguingly, upon viral infection the biomass of eukaryotic heterotrophs (thraustochytrids) rivals that of bacteria as potential recyclers of organic matter. 36720878 6 31 theme matter 1164:1169 arg1 that 1113:1116 that 1113:1116 that 1113:1116 Intriguingly, upon viral infection the biomass of eukaryotic heterotrophs (thraustochytrids) rivals that of bacteria as potential recyclers of organic matter. 36720878 8 32 theme organic 1616:1622 arg1 matter 1624:1629 organic matter 1616:1629 organic matter in large-scale coccolithophore blooms 1616:1667 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 7 33 theme per-cell 1331:1338 arg1 rates 1340:1344 per-cell rates 1331:1344 per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean 1331:1509 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 3 34 theme carbon 492:497 arg1 fate 484:487 the fate 480:487 the fate of carbon 480:497 Viral infection can lead to bloom termination, but its impact on the fate of carbon remains largely unquantified. 36720878 1 35 theme elemental 239:247 arg1 cycling 249:255 global elemental cycling 232:255 global elemental cycling 232:255 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 7 36 from release 1370:1376 arg1 form 1385:1388 the form 1381:1388 the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking 1381:1489 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 6 37 theme potential 1133:1141 arg1 recyclers 1143:1151 potential recyclers 1133:1151 potential recyclers of organic matter 1133:1169 Intriguingly, upon viral infection the biomass of eukaryotic heterotrophs (thraustochytrids) rivals that of bacteria as potential recyclers of organic matter. 36720878 6 37 theme potential 1133:1141 arg1 that 1113:1116 that 1113:1116 that 1113:1116 Intriguingly, upon viral infection the biomass of eukaryotic heterotrophs (thraustochytrids) rivals that of bacteria as potential recyclers of organic matter. 36720878 8 38 theme coccolithophore 1646:1660 arg1 blooms 1662:1667 large-scale coccolithophore blooms 1634:1667 large-scale coccolithophore blooms 1634:1667 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 2 39 theme higher 351:356 arg1 sinking 406:412 sinking 406:412 sinking 406:412 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 2 39 theme higher 351:356 arg1 production 392:401 bacterial biomass production 374:401 bacterial biomass production 374:401 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 2 39 theme higher 351:356 arg1 levels 366:371 either higher trophic levels 344:371 either higher trophic levels 344:371 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 7 40 theme viral 1285:1289 arg1 infection 1291:1299 viral infection 1285:1299 viral infection 1285:1299 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 2 41 theme organic 284:290 arg1 carbon 292:297 organic carbon 284:297 organic carbon 284:297 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 7 42 theme deep 1500:1503 arg1 ocean 1505:1509 the deep ocean 1496:1509 the deep ocean 1496:1509 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 4 43 theme viral 573:577 arg1 infection 579:587 viral infection 573:587 viral infection 573:587 Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. 36720878 8 44 from matter 1624:1629 arg1 blooms 1662:1667 large-scale coccolithophore blooms 1634:1667 large-scale coccolithophore blooms 1634:1667 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 2 45 theme bloom 277:281 arg1 demise 263:268 demise 263:268 demise of the bloom 263:281 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 1 46 theme production 173:182 arg1 blooms 135:140 Algal blooms 129:140 Algal blooms 129:140 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 1 46 theme production 173:182 arg1 hotspots 146:153 hotspots 146:153 hotspots of marine primary production 146:182 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 0 47 theme bacterial 45:53 arg1 recyclers 70:78 bacterial and eukaryotic recyclers 45:78 bacterial and eukaryotic recyclers of organic matter 45:96 Viral infection switches the balance between bacterial and eukaryotic recyclers of organic matter during coccolithophore blooms. 36720878 3 48 from impact 470:475 arg1 fate 484:487 the fate 480:487 the fate of carbon 480:497 Viral infection can lead to bloom termination, but its impact on the fate of carbon remains largely unquantified. 36720878 7 49 theme major 1454:1458 arg1 polysaccharides 1400:1414 acidic polysaccharides 1393:1414 acidic polysaccharides 1393:1414 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 7 49 theme major 1454:1458 arg1 contributors 1460:1471 two major contributors 1450:1471 two major contributors to carbon sinking 1450:1489 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 4 50 theme evolving 663:670 arg1 landscape 687:695 the evolving biogeochemical landscape 659:695 the evolving biogeochemical landscape 659:695 Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. 36720878 8 51 from blooms 1662:1667 arg1 recyclers 1603:1611 microbial recyclers 1593:1611 microbial recyclers of organic matter in large-scale coccolithophore blooms 1593:1667 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 5 52 theme viral 890:894 arg1 infection 896:904 viral infection 890:904 viral infection 890:904 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 1 53 theme microbial 210:218 arg1 ecology 220:226 microbial ecology 210:226 microbial ecology 210:226 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 7 54 theme inorganic 1432:1440 arg1 carbon 1442:1447 particulate inorganic carbon 1420:1447 particulate inorganic carbon 1420:1447 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 4 55 theme microbiome 631:640 arg1 interplay 555:563 the interplay 551:563 the interplay between viral infection 551:587 Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. 36720878 4 55 theme microbiome 631:640 arg1 composition 597:607 the composition 593:607 the composition of a bloom-associated microbiome 593:640 Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. 36720878 5 56 theme significant 922:932 arg1 shifts 934:939 significant shifts 922:939 significant shifts in the composition of free-living bacterial and eukaryotic assemblages 922:1010 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 7 57 theme acidic 1393:1398 arg1 contributors 1460:1471 two major contributors 1450:1471 two major contributors to carbon sinking 1450:1489 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 7 57 theme acidic 1393:1398 arg1 polysaccharides 1400:1414 acidic polysaccharides 1393:1414 acidic polysaccharides 1393:1414 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 4 58 theme mesocosm 726:733 arg1 experiment 735:744 a large-scale mesocosm experiment 712:744 a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms 712:798 Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. 36720878 5 59 theme infection 896:904 arg1 levels 880:885 only high levels 870:885 only high levels of viral infection 870:904 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 7 60 theme single-cell 1244:1254 arg1 resolution 1256:1265 a single-cell resolution 1242:1265 a single-cell resolution 1242:1265 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 0 61 theme organic 83:89 arg1 matter 91:96 organic matter 83:96 organic matter 83:96 Viral infection switches the balance between bacterial and eukaryotic recyclers of organic matter during coccolithophore blooms. 36720878 1 62 theme marine 158:163 arg1 production 173:182 marine primary production 158:182 marine primary production 158:182 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 6 63 theme viral 1032:1036 arg1 infection 1038:1046 viral infection 1032:1046 viral infection 1032:1046 Intriguingly, upon viral infection the biomass of eukaryotic heterotrophs (thraustochytrids) rivals that of bacteria as potential recyclers of organic matter. 36720878 8 64 theme viral 1547:1551 arg1 infection 1553:1561 viral infection 1547:1561 viral infection 1547:1561 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 4 65 theme induced 769:775 arg1 blooms 793:798 seven induced coccolithophore blooms 763:798 seven induced coccolithophore blooms 763:798 Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. 36720878 7 66 theme infection 1229:1237 arg1 modeling 1185:1192 modeling 1185:1192 modeling 1185:1192 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 7 66 theme infection 1229:1237 arg1 quantification 1198:1211 quantification 1198:1211 quantification 1198:1211 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 5 67 theme assemblages 1000:1010 arg1 composition 948:958 the composition 944:958 the composition of free-living bacterial and eukaryotic assemblages 944:1010 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 7 68 from form 1385:1388 arg1 rates 1340:1344 per-cell rates 1331:1344 per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean 1331:1509 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 7 69 theme release 1370:1376 arg1 rates 1340:1344 per-cell rates 1331:1344 per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean 1331:1509 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 2 70 theme biomass 384:390 arg1 production 392:401 bacterial biomass production 374:401 bacterial biomass production 374:401 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 2 70 theme biomass 384:390 arg1 levels 366:371 either higher trophic levels 344:371 either higher trophic levels 344:371 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 7 71 theme active 1216:1221 arg1 infection 1229:1237 active viral infection 1216:1237 active viral infection 1216:1237 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 7 72 theme extracellular 1349:1361 arg1 release 1370:1376 extracellular carbon release 1349:1376 extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean 1349:1509 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 8 73 theme carbon 1578:1583 arg1 fate 1570:1573 the fate 1566:1573 the fate of carbon 1566:1583 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 5 74 theme viral 838:842 arg1 infection 844:852 viral infection 838:852 viral infection 838:852 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 5 75 from shifts 934:939 arg1 composition 948:958 the composition 944:958 the composition of free-living bacterial and eukaryotic assemblages 944:1010 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 5 76 theme free-living 963:973 arg1 assemblages 1000:1010 free-living bacterial and eukaryotic assemblages 963:1010 free-living bacterial and eukaryotic assemblages 963:1010 The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. 36720878 8 77 theme microbial 1593:1601 arg1 recyclers 1603:1611 microbial recyclers 1593:1611 microbial recyclers of organic matter in large-scale coccolithophore blooms 1593:1667 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 6 78 theme heterotrophs 1074:1085 arg1 biomass 1052:1058 the biomass 1048:1058 the biomass of eukaryotic heterotrophs (thraustochytrids) 1048:1104 Intriguingly, upon viral infection the biomass of eukaryotic heterotrophs (thraustochytrids) rivals that of bacteria as potential recyclers of organic matter. 36720878 3 79 theme Viral 415:419 arg1 infection 421:429 Viral infection 415:429 Viral infection 415:429 Viral infection can lead to bloom termination, but its impact on the fate of carbon remains largely unquantified. 36720878 7 80 theme fold 1314:1317 arg1 increase 1319:1326 a 2-4 fold increase 1308:1326 a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean 1308:1509 By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. 36720878 8 81 theme matter 1624:1629 arg1 recyclers 1603:1611 microbial recyclers 1593:1611 microbial recyclers of organic matter in large-scale coccolithophore blooms 1593:1667 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 6 82 theme organic 1156:1162 arg1 matter 1164:1169 organic matter 1156:1169 organic matter 1156:1169 Intriguingly, upon viral infection the biomass of eukaryotic heterotrophs (thraustochytrids) rivals that of bacteria as potential recyclers of organic matter. 36720878 8 83 theme large-scale 1634:1644 arg1 blooms 1662:1667 large-scale coccolithophore blooms 1634:1667 large-scale coccolithophore blooms 1634:1667 These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms. 36720878 1 84 theme global 232:237 arg1 cycling 249:255 global elemental cycling 232:255 global elemental cycling 232:255 Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. 36720878 2 85 theme trophic 358:364 arg1 sinking 406:412 sinking 406:412 sinking 406:412 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 2 85 theme trophic 358:364 arg1 production 392:401 bacterial biomass production 374:401 bacterial biomass production 374:401 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 36720878 2 85 theme trophic 358:364 arg1 levels 366:371 either higher trophic levels 344:371 either higher trophic levels 344:371 Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. 37376005 4 0 theme polyphenols 678:688 arg1 sum 671:673 the sum 667:673 the sum of polyphenols and flavonoids 667:703 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 7 1 theme daily 1219:1223 arg1 consumption 1225:1235 daily consumption 1219:1235 daily consumption 1219:1235 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 2 2 theme health 476:481 arg1 risk 483:486 health risk 476:486 health risk 476:486 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 6 3 theme F. 966:967 arg1 samples 979:985 most Arctic F. distichus samples 954:985 most Arctic F. distichus samples 954:985 It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. 37376005 8 4 theme polysaccharides 1412:1426 arg1 distichus 1382:1390 Arctic F. distichus 1372:1390 Arctic F. distichus 1372:1390 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 8 4 theme polysaccharides 1412:1426 arg1 source 1402:1407 a rich source 1395:1407 a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity 1395:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 4 5 from WS 747:748 arg1 samples 718:724 samples 718:724 samples of F. distichus from WS 718:748 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 7 6 theme studied 1167:1173 arg1 samples 1175:1181 all studied samples 1163:1181 all studied samples of Arctic F. distichus 1163:1204 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 9 7 theme algae 1605:1609 arg1 use 1593:1595 the use 1589:1595 the use of this algae as a promising and safe raw material for the food and pharmaceutical industries 1589:1689 We believe that our data will help to effectively use the potential of F. distichus and expand the use of this algae as a promising and safe raw material for the food and pharmaceutical industries. 37376005 8 8 theme polyphenols 1429:1439 arg1 distichus 1382:1390 Arctic F. distichus 1372:1390 Arctic F. distichus 1372:1390 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 8 8 theme polyphenols 1429:1439 arg1 source 1402:1407 a rich source 1395:1407 a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity 1395:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 7 9 theme distichus 1196:1204 arg1 samples 1175:1181 all studied samples 1163:1181 all studied samples of Arctic F. distichus 1163:1204 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 4 10 theme sum 671:673 arg1 level 658:662 The highest level 646:662 The highest level of the sum of polyphenols and flavonoids 646:703 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 4 10 theme sum 671:673 arg1 located 758:764 located 758:764 located 758:764 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 2 11 theme geographic 274:283 arg1 location 285:292 the geographic location 270:292 the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) 270:400 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 7 12 theme index 1149:1153 arg1 values 1155:1160 hazard index values 1142:1160 hazard index values 1142:1160 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 4 13 located found 709:713 arg2 level 658:662 The highest level 646:662 The highest level of the sum of polyphenols and flavonoids 646:703 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 4 13 located found 709:713 arg1 samples 718:724 samples 718:724 samples of F. distichus from WS 718:748 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 4 13 located found 709:713 arg2 located 758:764 located 758:764 located 758:764 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 3 14 theme dry 602:604 arg1 DW 614:615 DW 614:615 DW 614:615 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 3 14 theme dry 602:604 arg1 weight 606:611 335 mg/g dry weight 593:611 335 mg/g dry weight (DW) 593:616 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 3 15 dep 445 627:629 arg1 to 624:625 to 624:625 to 624:625 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 1 16 theme intertidal 188:197 arg1 areas 199:203 the rocky intertidal areas 178:203 the rocky intertidal areas of the Arctic and Subarctic 178:231 Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. 37376005 9 17 theme raw 1635:1637 arg1 material 1639:1646 a promising and safe raw material 1614:1646 a promising and safe raw material for the food and pharmaceutical industries 1614:1689 We believe that our data will help to effectively use the potential of F. distichus and expand the use of this algae as a promising and safe raw material for the food and pharmaceutical industries. 37376005 3 18 dep DW 636:637 arg1 mg/g 631:634 mg/g 631:634 mg/g 631:634 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 8 19 theme antiradical 1472:1482 arg1 activity 1484:1491 important antiradical activity 1462:1491 important antiradical activity 1462:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 1 20 dep Arctic 212:217 arg1 the 208:210 the 208:210 the 208:210 Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. 37376005 7 21 theme hazard 1122:1127 arg1 quotient 1129:1136 calculated targeted hazard quotient 1102:1136 calculated targeted hazard quotient 1102:1136 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 4 22 from samples 718:724 arg1 WS 747:748 WS 747:748 WS 747:748 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 4 23 theme flavonoids 694:703 arg1 sum 671:673 the sum 667:673 the sum of polyphenols and flavonoids 667:703 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 2 24 theme antiradical 448:458 arg1 properties 460:469 antiradical properties 448:469 antiradical properties 448:469 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 7 25 theme calculated 1102:1111 arg1 quotient 1129:1136 calculated targeted hazard quotient 1102:1136 calculated targeted hazard quotient 1102:1136 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 9 26 theme food 1656:1659 arg1 industries 1680:1689 the food and pharmaceutical industries 1652:1689 the food and pharmaceutical industries 1652:1689 We believe that our data will help to effectively use the potential of F. distichus and expand the use of this algae as a promising and safe raw material for the food and pharmaceutical industries. 37376005 2 27 from impact 260:265 arg1 variations 409:418 the variations 405:418 the variations in biochemical composition, antiradical properties, and health risk 405:486 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 9 28 theme pharmaceutical 1665:1678 arg1 industries 1680:1689 the food and pharmaceutical industries 1652:1689 the food and pharmaceutical industries 1652:1689 We believe that our data will help to effectively use the potential of F. distichus and expand the use of this algae as a promising and safe raw material for the food and pharmaceutical industries. 37376005 0 29 theme Biochemical 45:55 arg1 Composition 57:67 Biochemical Composition 45:67 Biochemical Composition 45:67 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 7 30 theme children 1304:1311 arg1 health 1284:1289 the health 1280:1289 the health of adults or children 1280:1311 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 2 31 theme Barents 385:391 arg1 Sea 393:395 Barents Sea 385:395 Barents Sea (BS) 385:400 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 2 31 theme Barents 385:391 arg1 BS 398:399 BS 398:399 BS 398:399 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 8 32 with polyphenols 1429:1439 arg1 activity 1484:1491 important antiradical activity 1462:1491 important antiradical activity 1462:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 4 33 located located 758:764 arg2 level 658:662 The highest level 646:662 The highest level of the sum of polyphenols and flavonoids 646:703 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 4 33 located located 758:764 arg1 order 791:795 the following ranking order 769:795 the following ranking order 769:795 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 4 33 located located 758:764 arg2 located 758:764 located 758:764 located 758:764 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 1 34 theme dominant 141:148 arg1 macroalga 165:173 the dominant canopy-forming macroalga 137:173 the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic 137:231 Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. 37376005 1 34 theme dominant 141:148 arg1 L. 131:132 Fucus distichus L. 115:132 Fucus distichus L. 115:132 Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. 37376005 7 35 theme adults 1294:1299 arg1 health 1284:1289 the health 1280:1289 the health of adults or children 1280:1311 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 8 36 with polysaccharides 1412:1426 arg1 activity 1484:1491 important antiradical activity 1462:1491 important antiradical activity 1462:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 5 37 theme seaweed 883:889 arg1 activity 871:878 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity 818:878 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed 818:889 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed is correlated with its phenolic content. 37376005 7 38 theme Arctic 1186:1191 arg1 distichus 1196:1204 Arctic F. distichus 1186:1204 Arctic F. distichus 1186:1204 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 0 39 theme Human 96:100 arg1 Risk 109:112 Human Health Risk 96:112 Human Health Risk 96:112 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 4 40 theme < 807:807 arg1 WS 814:815 < NS < WS 807:815 < NS < WS 807:815 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 2 41 dep F. 297:298 arg1 distichus 300:308 F. distichus 297:308 F. distichus collected in the Baffin Sea (BfS) 297:342 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 0 42 theme Arctic 0:5 arg1 L. 41:42 Arctic Edible Brown Alga Fucus distichus L. 0:42 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 0:113 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 4 43 theme < 812:812 arg1 WS 814:815 < NS < WS 807:815 < NS < WS 807:815 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 0 44 theme Brown 14:18 arg1 L. 41:42 Arctic Edible Brown Alga Fucus distichus L. 0:42 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 0:113 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 2 45 theme Sea 355:357 arg1 location 285:292 the geographic location 270:292 the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) 270:400 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 0 46 theme Fucus 25:29 arg1 L. 41:42 Arctic Edible Brown Alga Fucus distichus L. 0:42 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 0:113 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 0 47 dep L. 41:42 arg1 Risk 109:112 Human Health Risk 96:112 Human Health Risk 96:112 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 0 47 dep L. 41:42 arg1 Composition 57:67 Biochemical Composition 45:67 Biochemical Composition 45:67 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 0 47 dep L. 41:42 arg1 Potential 82:90 Antiradical Potential 70:90 Antiradical Potential 70:90 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 3 48 theme main 523:526 arg1 carbohydrates 528:540 main carbohydrates 523:540 main carbohydrates (fucoidan, mannitol, and alginic acid) 523:579 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 3 48 theme main 523:526 arg1 acid 575:578 alginic acid 567:578 alginic acid 567:578 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 3 48 theme main 523:526 arg1 mannitol 553:560 mannitol 553:560 mannitol 553:560 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 3 48 theme main 523:526 arg1 fucoidan 543:550 fucoidan 543:550 fucoidan 543:550 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 4 49 theme highest 650:656 arg1 level 658:662 The highest level 646:662 The highest level of the sum of polyphenols and flavonoids 646:703 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 4 49 theme highest 650:656 arg1 located 758:764 located 758:764 located 758:764 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 3 50 from DW 636:637 arg1 BS 642:643 BS 642:643 BS 642:643 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 2 51 theme F. 297:298 arg1 Sea 355:357 F. distichus collected in the Baffin Sea (BfS), Norwegian Sea 297:357 F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS) 297:362 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 2 51 theme F. 297:298 arg1 NS 360:361 NS 360:361 NS 360:361 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 9 52 theme distichus 1568:1576 arg1 potential 1552:1560 the potential 1548:1560 the potential of F. distichus 1548:1576 We believe that our data will help to effectively use the potential of F. distichus and expand the use of this algae as a promising and safe raw material for the food and pharmaceutical industries. 37376005 2 53 from variations 409:418 arg1 risk 483:486 health risk 476:486 health risk 476:486 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 2 53 from variations 409:418 arg1 composition 435:445 biochemical composition 423:445 biochemical composition 423:445 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 2 53 from variations 409:418 arg1 properties 460:469 antiradical properties 448:469 antiradical properties 448:469 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 8 54 theme F. 1379:1380 arg1 distichus 1382:1390 Arctic F. distichus 1372:1390 Arctic F. distichus 1372:1390 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 8 54 theme F. 1379:1380 arg1 source 1402:1407 a rich source 1395:1407 a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity 1395:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 3 55 dep carbohydrates 528:540 arg1 acid 575:578 alginic acid 567:578 alginic acid 567:578 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 3 55 dep carbohydrates 528:540 arg1 carbohydrates 528:540 main carbohydrates 523:540 main carbohydrates (fucoidan, mannitol, and alginic acid) 523:579 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 3 55 dep carbohydrates 528:540 arg1 mannitol 553:560 mannitol 553:560 mannitol 553:560 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 3 55 dep carbohydrates 528:540 arg1 fucoidan 543:550 fucoidan 543:550 fucoidan 543:550 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 4 56 theme ranking 783:789 arg1 order 791:795 the following ranking order 769:795 the following ranking order 769:795 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 4 57 from located 758:764 arg1 order 791:795 the following ranking order 769:795 the following ranking order 769:795 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 3 58 theme alginic 567:573 arg1 acid 575:578 alginic acid 567:578 alginic acid 567:578 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 3 58 theme alginic 567:573 arg1 carbohydrates 528:540 main carbohydrates 523:540 main carbohydrates (fucoidan, mannitol, and alginic acid) 523:579 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 8 59 theme rich 1397:1400 arg1 distichus 1382:1390 Arctic F. distichus 1372:1390 Arctic F. distichus 1372:1390 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 8 59 theme rich 1397:1400 arg1 source 1402:1407 a rich source 1395:1407 a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity 1395:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 6 60 theme Arctic 959:964 arg1 samples 979:985 most Arctic F. distichus samples 954:985 most Arctic F. distichus samples 954:985 It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. 37376005 3 61 theme mg/g 597:600 arg1 DW 614:615 DW 614:615 DW 614:615 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 3 61 theme mg/g 597:600 arg1 weight 606:611 335 mg/g dry weight 593:611 335 mg/g dry weight (DW) 593:616 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 1 62 theme canopy-forming 150:163 arg1 macroalga 165:173 the dominant canopy-forming macroalga 137:173 the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic 137:231 Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. 37376005 1 62 theme canopy-forming 150:163 arg1 L. 131:132 Fucus distichus L. 115:132 Fucus distichus L. 115:132 Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. 37376005 7 63 theme F. 1193:1194 arg1 distichus 1196:1204 Arctic F. distichus 1186:1204 Arctic F. distichus 1186:1204 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 2 64 theme location 285:292 arg1 impact 260:265 the impact 256:265 the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk 256:486 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 9 65 theme promising 1616:1624 arg1 material 1639:1646 a promising and safe raw material 1614:1646 a promising and safe raw material for the food and pharmaceutical industries 1614:1689 We believe that our data will help to effectively use the potential of F. distichus and expand the use of this algae as a promising and safe raw material for the food and pharmaceutical industries. 37376005 1 66 theme rocky 182:186 arg1 areas 199:203 the rocky intertidal areas 178:203 the rocky intertidal areas of the Arctic and Subarctic 178:231 Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. 37376005 2 67 theme biochemical 423:433 arg1 composition 435:445 biochemical composition 423:445 biochemical composition 423:445 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 9 68 theme safe 1630:1633 arg1 material 1639:1646 a promising and safe raw material 1614:1646 a promising and safe raw material for the food and pharmaceutical industries 1614:1689 We believe that our data will help to effectively use the potential of F. distichus and expand the use of this algae as a promising and safe raw material for the food and pharmaceutical industries. 37376005 5 69 theme scavenging 860:869 arg1 activity 871:878 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity 818:878 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed 818:889 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed is correlated with its phenolic content. 37376005 8 70 theme flavonoids 1446:1455 arg1 distichus 1382:1390 Arctic F. distichus 1372:1390 Arctic F. distichus 1372:1390 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 8 70 theme flavonoids 1446:1455 arg1 source 1402:1407 a rich source 1395:1407 a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity 1395:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 4 71 theme distichus 732:740 arg1 samples 718:724 samples 718:724 samples of F. distichus from WS 718:748 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 7 72 theme hazard 1142:1147 arg1 values 1155:1160 hazard index values 1142:1160 hazard index values 1142:1160 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 8 73 theme important 1462:1470 arg1 activity 1484:1491 important antiradical activity 1462:1491 important antiradical activity 1462:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 6 74 dep quantification 1073:1086 arg1 the 1060:1062 the 1060:1062 the 1060:1062 It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. 37376005 6 74 dep quantification 1073:1086 arg1 limit 1064:1068 limit 1064:1068 limit 1064:1068 It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. 37376005 2 75 theme present 241:247 arg1 study 249:253 the present study 237:253 the present study 237:253 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 7 76 theme targeted 1113:1120 arg1 quotient 1129:1136 calculated targeted hazard quotient 1102:1136 calculated targeted hazard quotient 1102:1136 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 5 77 theme 2,2-diphenyl-1-picrylhydrazyl 822:850 arg1 activity 871:878 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity 818:878 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed 818:889 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed is correlated with its phenolic content. 37376005 2 78 theme Sea 393:395 arg1 location 285:292 the geographic location 270:292 the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) 270:400 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 6 79 theme distichus 969:977 arg1 samples 979:985 most Arctic F. distichus samples 954:985 most Arctic F. distichus samples 954:985 It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. 37376005 0 80 theme Antiradical 70:80 arg1 Potential 82:90 Antiradical Potential 70:90 Antiradical Potential 70:90 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 5 81 theme phenolic 914:921 arg1 content 923:929 its phenolic content 910:929 its phenolic content 910:929 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed is correlated with its phenolic content. 37376005 1 82 from macroalga 165:173 arg1 areas 199:203 the rocky intertidal areas 178:203 the rocky intertidal areas of the Arctic and Subarctic 178:231 Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. 37376005 4 83 theme following 773:781 arg1 order 791:795 the following ranking order 769:795 the following ranking order 769:795 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 5 84 theme radical 852:858 arg1 activity 871:878 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity 818:878 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed 818:889 The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed is correlated with its phenolic content. 37376005 0 85 theme Health 102:107 arg1 Risk 109:112 Human Health Risk 96:112 Human Health Risk 96:112 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 8 86 with flavonoids 1446:1455 arg1 activity 1484:1491 important antiradical activity 1462:1491 important antiradical activity 1462:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 0 87 theme Edible 7:12 arg1 L. 41:42 Arctic Edible Brown Alga Fucus distichus L. 0:42 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 0:113 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 2 88 theme White 365:369 arg1 WS 376:377 WS 376:377 WS 376:377 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 2 88 theme White 365:369 arg1 Sea 371:373 White Sea 365:373 White Sea (WS) 365:378 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 3 89 dep mg/g 631:634 arg1 445 627:629 445 627:629 445 627:629 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 0 90 theme Alga 20:23 arg1 L. 41:42 Arctic Edible Brown Alga Fucus distichus L. 0:42 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 0:113 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 4 91 theme NS 809:810 arg1 WS 814:815 < NS < WS 807:815 < NS < WS 807:815 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 3 92 theme carbohydrates 528:540 arg1 accumulation 507:518 The accumulation 503:518 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) 503:579 The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. 37376005 0 93 theme distichus 31:39 arg1 L. 41:42 Arctic Edible Brown Alga Fucus distichus L. 0:42 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 0:113 Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. 37376005 6 94 located detected 1016:1023 arg2 Pb 996:997 Pb 996:997 Pb 996:997 It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. 37376005 6 94 located detected 1016:1023 arg2 Cr 992:993 Cr 992:993 Cr 992:993 It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. 37376005 6 94 located detected 1016:1023 arg2 Cd 988:989 Cd 988:989 Cd 988:989 It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. 37376005 6 94 located detected 1016:1023 arg1 samples 979:985 most Arctic F. distichus samples 954:985 most Arctic F. distichus samples 954:985 It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. 37376005 6 94 located detected 1016:1023 arg2 Ni 1004:1005 Ni 1004:1005 Ni 1004:1005 It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. 37376005 7 95 theme carcinogenic 1259:1270 arg1 risk 1272:1275 a carcinogenic risk 1257:1275 a carcinogenic risk to the health of adults or children 1257:1311 According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. 37376005 4 96 theme BS 798:799 arg1 < 801:801 BS < 798:801 BS < 798:801 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 8 97 theme Arctic 1372:1377 arg1 distichus 1382:1390 Arctic F. distichus 1372:1390 Arctic F. distichus 1372:1390 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 8 97 theme Arctic 1372:1377 arg1 source 1402:1407 a rich source 1395:1407 a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity 1395:1491 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 4 98 from order 791:795 arg1 level 658:662 The highest level 646:662 The highest level of the sum of polyphenols and flavonoids 646:703 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 4 98 from order 791:795 arg1 located 758:764 located 758:764 located 758:764 The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. 37376005 9 99 theme F. 1565:1566 arg1 distichus 1568:1576 F. distichus 1565:1576 F. distichus 1565:1576 We believe that our data will help to effectively use the potential of F. distichus and expand the use of this algae as a promising and safe raw material for the food and pharmaceutical industries. 37376005 2 100 theme Baffin 327:332 arg1 BfS 339:341 BfS 339:341 BfS 339:341 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 2 100 theme Baffin 327:332 arg1 Sea 334:336 the Baffin Sea 323:336 the Baffin Sea (BfS) 323:342 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 1 101 theme Arctic 212:217 arg1 areas 199:203 the rocky intertidal areas 178:203 the rocky intertidal areas of the Arctic and Subarctic 178:231 Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. 37376005 8 102 theme study 1334:1338 arg1 results 1318:1324 The results 1314:1324 The results of this study 1314:1338 The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. 37376005 2 103 theme Sea 371:373 arg1 location 285:292 the geographic location 270:292 the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) 270:400 In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. 37376005 1 104 theme Subarctic 223:231 arg1 areas 199:203 the rocky intertidal areas 178:203 the rocky intertidal areas of the Arctic and Subarctic 178:231 Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. 36834184 7 0 theme carbon 1241:1246 arg1 content 1248:1254 the higher carbon content 1230:1254 the higher carbon content in BAF (0-5 cm) 1230:1270 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 2 1 theme forest 342:347 arg1 regrowth 349:356 post-fire forest regrowth 332:356 post-fire forest regrowth 332:356 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 4 2 theme molecular 597:605 arg1 changes 607:613 molecular changes 597:613 molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 597:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 10 3 from abundant 1456:1463 arg1 NAF 1468:1470 NAF 1468:1470 NAF 1468:1470 UACs and PAH compounds were abundant in NAF, possibly air-transported from BAF. 36834184 5 4 theme compounds 839:847 arg1 abundance 806:814 increased abundance 796:814 increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) 796:962 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 2 5 theme post-fire 332:340 arg1 regrowth 349:356 post-fire forest regrowth 332:356 post-fire forest regrowth 332:356 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 5 6 theme aromatic 830:837 arg1 compounds 839:847 unspecific aromatic compounds 819:847 unspecific aromatic compounds (UACs) 819:854 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 5 6 theme aromatic 830:837 arg1 UACs 850:853 UACs 850:853 UACs 850:853 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 5 7 from effects 990:996 arg1 SOM 1009:1011 SOM 1009:1011 SOM 1009:1011 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 4 8 theme native 761:766 arg1 NAF 772:774 NAF 772:774 NAF 772:774 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 4 8 theme native 761:766 arg1 AF 768:769 native AF 761:769 native AF (NAF) 761:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 2 9 theme SOM 280:282 arg1 driver 322:327 a principal driver 310:327 a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience 310:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 9 theme SOM 280:282 arg1 composition 295:305 soil organic matter (SOM) molecular composition 259:305 soil organic matter (SOM) molecular composition 259:305 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 4 10 from changes 607:613 arg1 depth 638:642 0-10, 40-50 cm depth 623:642 depth 638:642 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 4 10 from changes 607:613 arg1 SOM 618:620 SOM 618:620 SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 618:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 5 11 theme fire 1001:1004 arg1 effects 990:996 strong lingering effects 973:996 strong lingering effects of fire on SOM 973:1011 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 6 12 theme SOM 1078:1080 arg1 recovery 1090:1097 SOM minimal recovery 1078:1097 SOM minimal recovery 1078:1097 This occurs despite fresh litter deposition on soil, suggesting SOM minimal recovery and toxicity to microorganisms. 36834184 7 13 theme compounds 1160:1168 arg1 Accumulation 1131:1142 Accumulation 1131:1142 Accumulation of recalcitrant compounds 1131:1168 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 7 13 theme compounds 1160:1168 arg1 decomposition 1179:1191 slow decomposition 1174:1191 slow decomposition of fresh forest material 1174:1216 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 4 14 theme pasture 717:723 arg1 site 744:747 a 23-year Brachiaria pasture post-AF fire (BRA) site 696:747 a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 696:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 4 15 theme Brachiaria 706:715 arg1 site 744:747 a 23-year Brachiaria pasture post-AF fire (BRA) site 696:747 a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 696:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 9 16 theme hydroaromatic 1351:1363 arg1 compounds 1365:1373 alkyl and hydroaromatic compounds 1341:1373 alkyl and hydroaromatic compounds 1341:1373 At 40-50 cm, alkyl and hydroaromatic compounds accumulated in BRA, whereas UACs accumulated in BAF. 36834184 6 17 theme fresh 1034:1038 arg1 deposition 1047:1056 fresh litter deposition 1034:1056 fresh litter deposition on soil 1034:1064 This occurs despite fresh litter deposition on soil, suggesting SOM minimal recovery and toxicity to microorganisms. 36834184 5 18 theme hydrocarbons 877:888 arg1 abundance 806:814 increased abundance 796:814 increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) 796:962 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 2 19 theme matter 272:277 arg1 driver 322:327 a principal driver 310:327 a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience 310:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 19 theme matter 272:277 arg1 composition 295:305 soil organic matter (SOM) molecular composition 259:305 soil organic matter (SOM) molecular composition 259:305 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 3 20 theme SOM 418:420 arg1 shifts 431:436 SOM chemical shifts 418:436 SOM chemical shifts caused by AF fires and post-fire vegetation 418:480 Nevertheless, SOM chemical shifts caused by AF fires and post-fire vegetation are rarely investigated at a molecular level. 36834184 2 21 theme anti-wildfire 380:392 arg1 ambience 394:401 AF anti-wildfire ambience 377:401 AF anti-wildfire ambience 377:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 10 22 theme PAH 1437:1439 arg1 compounds 1441:1449 UACs and PAH compounds 1428:1449 UACs and PAH compounds 1428:1449 UACs and PAH compounds were abundant in NAF, possibly air-transported from BAF. 36834184 2 23 theme organic 264:270 arg1 driver 322:327 a principal driver 310:327 a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience 310:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 23 theme organic 264:270 arg1 composition 295:305 soil organic matter (SOM) molecular composition 259:305 soil organic matter (SOM) molecular composition 259:305 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 24 theme AF 377:378 arg1 ambience 394:401 AF anti-wildfire ambience 377:401 AF anti-wildfire ambience 377:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 0 25 theme Organic 5:11 arg1 Composition 30:40 Soil Organic Matter Molecular Composition 0:40 Soil Organic Matter Molecular Composition 0:40 Soil Organic Matter Molecular Composition Shifts Driven by Forest Regrowth or Pasture after Slash-and-Burn of Amazon Forest. 36834184 3 26 theme molecular 511:519 arg1 level 521:525 a molecular level 509:525 a molecular level 509:525 Nevertheless, SOM chemical shifts caused by AF fires and post-fire vegetation are rarely investigated at a molecular level. 36834184 4 27 theme fire 733:736 arg1 site 744:747 a 23-year Brachiaria pasture post-AF fire (BRA) site 696:747 a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 696:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 1 28 theme pasture 166:172 arg1 establishment 174:186 pasture establishment 166:186 pasture establishment 166:186 Slash-and-burn of Amazon Forest (AF) for pasture establishment has increased the occurrence of AF wildfires. 36834184 0 29 theme Soil 0:3 arg1 Composition 30:40 Soil Organic Matter Molecular Composition 0:40 Soil Organic Matter Molecular Composition 0:40 Soil Organic Matter Molecular Composition Shifts Driven by Forest Regrowth or Pasture after Slash-and-Burn of Amazon Forest. 36834184 4 30 theme chromatography-mass 554:572 arg1 spectrometry 574:585 pyrolysis-gas chromatography-mass spectrometry 540:585 pyrolysis-gas chromatography-mass spectrometry 540:585 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 4 31 theme post-AF 725:731 arg1 site 744:747 a 23-year Brachiaria pasture post-AF fire (BRA) site 696:747 a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 696:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 6 32 from deposition 1047:1056 arg1 soil 1061:1064 soil 1061:1064 soil 1061:1064 This occurs despite fresh litter deposition on soil, suggesting SOM minimal recovery and toxicity to microorganisms. 36834184 2 33 theme restoration 362:372 arg1 driver 322:327 a principal driver 310:327 a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience 310:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 33 theme restoration 362:372 arg1 composition 295:305 soil organic matter (SOM) molecular composition 259:305 soil organic matter (SOM) molecular composition 259:305 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 0 34 theme Molecular 20:28 arg1 Composition 30:40 Soil Organic Matter Molecular Composition 0:40 Soil Organic Matter Molecular Composition 0:40 Soil Organic Matter Molecular Composition Shifts Driven by Forest Regrowth or Pasture after Slash-and-Burn of Amazon Forest. 36834184 4 35 theme pyrolysis-gas 540:552 arg1 spectrometry 574:585 pyrolysis-gas chromatography-mass spectrometry 540:585 pyrolysis-gas chromatography-mass spectrometry 540:585 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 5 36 theme polycyclic 857:866 arg1 PAHs 891:894 PAHs 891:894 PAHs 891:894 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 5 36 theme polycyclic 857:866 arg1 hydrocarbons 877:888 polycyclic aromatic hydrocarbons 857:888 polycyclic aromatic hydrocarbons (PAHs) 857:895 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 2 37 theme molecular 285:293 arg1 driver 322:327 a principal driver 310:327 a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience 310:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 37 theme molecular 285:293 arg1 composition 295:305 soil organic matter (SOM) molecular composition 259:305 soil organic matter (SOM) molecular composition 259:305 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 4 38 theme cm 635:636 arg1 depth 638:642 0-10, 40-50 cm depth 623:642 depth 638:642 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 4 38 theme cm 635:636 arg1 SOM 618:620 SOM 618:620 SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 618:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 0 39 theme Matter 13:18 arg1 Composition 30:40 Soil Organic Matter Molecular Composition 0:40 Soil Organic Matter Molecular Composition 0:40 Soil Organic Matter Molecular Composition Shifts Driven by Forest Regrowth or Pasture after Slash-and-Burn of Amazon Forest. 36834184 6 40 theme minimal 1082:1088 arg1 recovery 1090:1097 SOM minimal recovery 1078:1097 SOM minimal recovery 1078:1097 This occurs despite fresh litter deposition on soil, suggesting SOM minimal recovery and toxicity to microorganisms. 36834184 0 41 theme Forest 117:122 arg1 Slash-and-Burn 92:105 Slash-and-Burn 92:105 Slash-and-Burn of Amazon Forest 92:122 Soil Organic Matter Molecular Composition Shifts Driven by Forest Regrowth or Pasture after Slash-and-Burn of Amazon Forest. 36834184 5 42 theme strong 973:978 arg1 effects 990:996 strong lingering effects 973:996 strong lingering effects of fire on SOM 973:1011 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 6 43 theme litter 1040:1045 arg1 deposition 1047:1056 fresh litter deposition 1034:1056 fresh litter deposition on soil 1034:1064 This occurs despite fresh litter deposition on soil, suggesting SOM minimal recovery and toxicity to microorganisms. 36834184 4 44 theme AF 683:684 arg1 depth 638:642 0-10, 40-50 cm depth 623:642 depth 638:642 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 4 44 theme AF 683:684 arg1 SOM 618:620 SOM 618:620 SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 618:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 5 45 theme lingering 980:988 arg1 effects 990:996 strong lingering effects 973:996 strong lingering effects of fire on SOM 973:1011 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 3 46 theme chemical 422:429 arg1 shifts 431:436 SOM chemical shifts 418:436 SOM chemical shifts caused by AF fires and post-fire vegetation 418:480 Nevertheless, SOM chemical shifts caused by AF fires and post-fire vegetation are rarely investigated at a molecular level. 36834184 7 47 theme material 1209:1216 arg1 Accumulation 1131:1142 Accumulation 1131:1142 Accumulation of recalcitrant compounds 1131:1168 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 7 47 theme material 1209:1216 arg1 decomposition 1179:1191 slow decomposition 1174:1191 slow decomposition of fresh forest material 1174:1216 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 2 48 theme ambience 394:401 arg1 restoration 362:372 restoration 362:372 restoration of AF anti-wildfire ambience 362:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 48 theme ambience 394:401 arg1 regrowth 349:356 post-fire forest regrowth 332:356 post-fire forest regrowth 332:356 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 5 49 theme lipids 901:906 arg1 abundance 806:814 increased abundance 796:814 increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) 796:962 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 0 50 dep Shifts 42:47 arg1 Driven 49:54 Driven 49:54 Shifts Driven by Forest Regrowth or Pasture after Slash-and-Burn of Amazon Forest 42:122 Soil Organic Matter Molecular Composition Shifts Driven by Forest Regrowth or Pasture after Slash-and-Burn of Amazon Forest. 36834184 4 51 theme 23-year 698:704 arg1 site 744:747 a 23-year Brachiaria pasture post-AF fire (BRA) site 696:747 a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 696:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 3 52 theme post-fire 461:469 arg1 vegetation 471:480 post-fire vegetation 461:480 post-fire vegetation 461:480 Nevertheless, SOM chemical shifts caused by AF fires and post-fire vegetation are rarely investigated at a molecular level. 36834184 5 53 theme polysaccharides 942:956 arg1 depletion 929:937 a depletion 927:937 a depletion of polysaccharides (Pol) 927:962 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 7 54 theme fresh 1196:1200 arg1 material 1209:1216 fresh forest material 1196:1216 fresh forest material 1196:1216 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 4 55 theme slash-burn-and-20-month-regrowth 650:681 arg1 BAF 687:689 BAF 687:689 BAF 687:689 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 4 55 theme slash-burn-and-20-month-regrowth 650:681 arg1 AF 683:684 a slash-burn-and-20-month-regrowth AF 648:684 a slash-burn-and-20-month-regrowth AF (BAF) 648:690 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 7 56 theme slow 1174:1177 arg1 decomposition 1179:1191 slow decomposition 1174:1191 slow decomposition of fresh forest material 1174:1216 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 5 57 theme aromatic 868:875 arg1 PAHs 891:894 PAHs 891:894 PAHs 891:894 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 5 57 theme aromatic 868:875 arg1 hydrocarbons 877:888 polycyclic aromatic hydrocarbons 857:888 polycyclic aromatic hydrocarbons (PAHs) 857:895 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 8 58 theme Brachiaria 1302:1311 arg1 contributions 1313:1325 Brachiaria contributions 1302:1325 Brachiaria contributions 1302:1325 In BRA, SOM was dominated by Brachiaria contributions. 36834184 2 59 theme soil 259:262 arg1 driver 322:327 a principal driver 310:327 a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience 310:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 59 theme soil 259:262 arg1 composition 295:305 soil organic matter (SOM) molecular composition 259:305 soil organic matter (SOM) molecular composition 259:305 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 60 theme principal 312:320 arg1 driver 322:327 a principal driver 310:327 a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience 310:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 60 theme principal 312:320 arg1 composition 295:305 soil organic matter (SOM) molecular composition 259:305 soil organic matter (SOM) molecular composition 259:305 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 4 61 theme BRA 739:741 arg1 site 744:747 a 23-year Brachiaria pasture post-AF fire (BRA) site 696:747 a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 696:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 7 62 theme forest 1202:1207 arg1 material 1209:1216 fresh forest material 1196:1216 fresh forest material 1196:1216 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 4 63 theme site 744:747 arg1 depth 638:642 0-10, 40-50 cm depth 623:642 depth 638:642 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 4 63 theme site 744:747 arg1 SOM 618:620 SOM 618:620 SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF) 618:775 We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). 36834184 1 64 theme Forest 150:155 arg1 Slash-and-burn 125:138 Slash-and-burn 125:138 Slash-and-burn of Amazon Forest (AF) for pasture establishment 125:186 Slash-and-burn of Amazon Forest (AF) for pasture establishment has increased the occurrence of AF wildfires. 36834184 7 65 theme higher 1234:1239 arg1 content 1248:1254 the higher carbon content 1230:1254 the higher carbon content in BAF (0-5 cm) 1230:1270 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 1 66 theme AF 220:221 arg1 wildfires 223:231 AF wildfires 220:231 AF wildfires 220:231 Slash-and-burn of Amazon Forest (AF) for pasture establishment has increased the occurrence of AF wildfires. 36834184 3 67 theme AF 448:449 arg1 fires 451:455 AF fires 448:455 AF fires 448:455 Nevertheless, SOM chemical shifts caused by AF fires and post-fire vegetation are rarely investigated at a molecular level. 36834184 9 68 theme alkyl 1341:1345 arg1 compounds 1365:1373 alkyl and hydroaromatic compounds 1341:1373 alkyl and hydroaromatic compounds 1341:1373 At 40-50 cm, alkyl and hydroaromatic compounds accumulated in BRA, whereas UACs accumulated in BAF. 36834184 5 69 theme unspecific 819:828 arg1 compounds 839:847 unspecific aromatic compounds 819:847 unspecific aromatic compounds (UACs) 819:854 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 5 69 theme unspecific 819:828 arg1 UACs 850:853 UACs 850:853 UACs 850:853 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 5 70 theme increased 796:804 arg1 abundance 806:814 increased abundance 796:814 increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) 796:962 In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. 36834184 1 71 theme wildfires 223:231 arg1 occurrence 206:215 the occurrence 202:215 the occurrence of AF wildfires 202:231 Slash-and-burn of Amazon Forest (AF) for pasture establishment has increased the occurrence of AF wildfires. 36834184 0 72 theme Forest 59:64 arg1 Regrowth 66:73 Forest Regrowth 59:73 Forest Regrowth 59:73 Soil Organic Matter Molecular Composition Shifts Driven by Forest Regrowth or Pasture after Slash-and-Burn of Amazon Forest. 36834184 10 73 from NAF 1468:1470 arg1 abundant 1456:1463 abundant 1456:1463 abundant 1456:1463 UACs and PAH compounds were abundant in NAF, possibly air-transported from BAF. 36834184 2 74 theme Recent 234:239 arg1 studies 241:247 Recent studies 234:247 Recent studies 234:247 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 7 75 from content 1248:1254 arg1 BAF 1259:1261 BAF 1259:1261 BAF (0-5 cm) 1259:1270 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 7 75 from content 1248:1254 arg1 cm 1268:1269 0-5 cm 1264:1269 0-5 cm 1264:1269 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 2 76 theme regrowth 349:356 arg1 driver 322:327 a principal driver 310:327 a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience 310:401 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 2 76 theme regrowth 349:356 arg1 composition 295:305 soil organic matter (SOM) molecular composition 259:305 soil organic matter (SOM) molecular composition 259:305 Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. 36834184 7 77 theme recalcitrant 1147:1158 arg1 compounds 1160:1168 recalcitrant compounds 1147:1168 recalcitrant compounds 1147:1168 Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). 36834184 10 78 theme UACs 1428:1431 arg1 compounds 1441:1449 UACs and PAH compounds 1428:1449 UACs and PAH compounds 1428:1449 UACs and PAH compounds were abundant in NAF, possibly air-transported from BAF. 36614214 9 0 theme combined 1390:1397 arg1 treatment 1399:1407 the combined treatment 1386:1407 the combined treatment of CCM 1386:1414 Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. 36614214 2 1 theme expensive 317:325 arg1 resources 327:335 the rare and expensive resources 304:335 the rare and expensive resources from natural habitats 304:357 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 11 2 theme line 1893:1896 arg1 HK-2 1898:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 11 3 theme epithelial 1877:1886 arg1 HK-2 1898:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 10 4 theme expression 1529:1538 arg1 down-regulation 1502:1516 CsA-induced down-regulation 1490:1516 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 1490:1624 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 6 5 theme acute 959:963 arg1 nephrotoxicity 965:978 CsA-induced acute nephrotoxicity 947:978 CsA-induced acute nephrotoxicity 947:978 CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). 36614214 10 6 theme channel 1557:1563 arg1 proteins 1565:1572 magnesium ion channel proteins 1543:1572 magnesium ion channel proteins 1543:1572 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 4 7 dep groups 724:729 arg1 control 732:738 control 732:738 control 732:738 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 4 7 dep groups 724:729 arg1 groups 724:729 six groups 720:729 six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally) 720:847 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 4 7 dep groups 724:729 arg1 CsA 809:811 CsA 809:811 CsA 809:811 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 4 7 dep groups 724:729 arg1 CCM 741:743 CCM 741:743 CCM (40 mg and 400 mg/kg, orally) 741:773 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 4 7 dep groups 724:729 arg1 CsA 776:778 CsA 776:778 CsA (10 mg/kg, oral gavage) 776:802 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 9 8 theme renal 1451:1455 arg1 tubules 1457:1463 renal tubules 1451:1463 renal tubules 1451:1463 Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. 36614214 10 9 theme magnesium 1543:1551 arg1 proteins 1565:1572 magnesium ion channel proteins 1543:1572 magnesium ion channel proteins 1543:1572 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 1 10 theme Cordyceps 199:207 arg1 CC 218:219 CC 218:219 CC 218:219 Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. 36614214 1 10 theme Cordyceps 199:207 arg1 cicadae 209:215 Cordyceps cicadae 199:215 Cordyceps cicadae (CC) 199:220 Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. 36614214 2 11 theme CC 507:508 arg1 sources 496:502 scarce sources 489:502 scarce sources of CC 489:508 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 6 12 theme nitrogen 1026:1033 arg1 levels 1005:1010 increased levels 995:1010 increased levels of blood urea nitrogen (BUN) 995:1039 CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). 36614214 0 13 theme Pathway 149:155 arg1 Reabsorption 98:109 Mg+2 Reabsorption 93:109 Mg+2 Reabsorption 93:109 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 36614214 0 13 theme Pathway 149:155 arg1 Inhibition 119:128 the Inhibition 115:128 the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro 115:177 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 36614214 10 14 theme receptor 1588:1595 arg1 melastatin 1607:1616 transient receptor potential melastatin 1578:1616 transient receptor potential melastatin 1578:1616 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 4 15 dep CCM 741:743 arg1 mg/kg 760:764 400 mg/kg 756:764 400 mg/kg 756:764 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 4 15 dep CCM 741:743 arg1 mg 749:750 40 mg 746:750 40 mg 746:750 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 11 16 theme proximal 1860:1867 arg1 HK-2 1898:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 6 17 theme blood 1015:1019 arg1 BUN 1036:1038 BUN 1036:1038 BUN 1036:1038 CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). 36614214 6 17 theme blood 1015:1019 arg1 nitrogen 1026:1033 blood urea nitrogen 1015:1033 blood urea nitrogen (BUN) 1015:1039 CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). 36614214 3 18 theme potential 546:554 arg1 effects 567:573 potential protective effects 546:573 potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity 546:638 However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. 36614214 11 19 theme human 1848:1852 arg1 HK-2 1898:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 12 20 theme functions 2076:2084 arg1 system 2060:2065 the defense system 2048:2065 the defense system of renal functions in CsA-induced acute nephrotoxicity 2048:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 10 21 dep proteins 1565:1572 arg1 6 1618:1618 6 1618:1618 6 1618:1618 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 10 21 dep proteins 1565:1572 arg1 7 1624:1624 7 1624:1624 7 1624:1624 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 3 22 theme cyclosporine 590:601 arg1 CsA 606:608 CsA 606:608 CsA 606:608 However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. 36614214 3 22 theme cyclosporine 590:601 arg1 A 603:603 cyclosporine A 590:603 cyclosporine A (CsA) 590:609 However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. 36614214 12 23 theme CsA-induced 2089:2099 arg1 nephrotoxicity 2107:2120 CsA-induced acute nephrotoxicity 2089:2120 CsA-induced acute nephrotoxicity 2089:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 7 24 theme protein 1120:1126 arg1 Levels 1042:1047 Levels 1042:1047 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) 1042:1138 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 5 25 from study 868:872 arg1 day 877:879 day 8 877:881 day 8 877:881 At the end of the study on day 8, all rats were sacrificed, and the blood and kidneys retrieved. 36614214 10 26 theme melastatin 1607:1616 arg1 down-regulation 1502:1516 CsA-induced down-regulation 1490:1516 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 1490:1624 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 8 27 theme oral 1265:1268 arg1 CCM 1280:1282 CCM 1280:1282 CCM (40 or 400 mg/kg) 1280:1300 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 27 theme oral 1265:1268 arg1 mg/kg 1295:1299 40 or 400 mg/kg 1285:1299 40 or 400 mg/kg 1285:1299 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 27 theme oral 1265:1268 arg1 CsA 1307:1309 CsA 1307:1309 CsA 1307:1309 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 27 theme oral 1265:1268 arg1 groups 1270:1275 synchronous oral groups 1253:1275 synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA 1253:1309 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 12 28 theme acute 2101:2105 arg1 nephrotoxicity 2107:2120 CsA-induced acute nephrotoxicity 2089:2120 CsA-induced acute nephrotoxicity 2089:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 11 29 theme cell 1888:1891 arg1 HK-2 1898:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 1 30 contain have 244:247 arg1 bodies 189:194 Fruiting bodies 180:194 Fruiting bodies of Cordyceps cicadae (CC) 180:220 Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. 36614214 1 30 contain have 244:247 arg2 effect 263:268 a therapeutic effect 249:268 a therapeutic effect 249:268 Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. 36614214 12 31 theme main 2011:2014 arg1 metabolites 2026:2036 the main secondary metabolites 2007:2036 the main secondary metabolites of CCM 2007:2043 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 12 32 theme nucleobases 1992:2002 arg1 role 1964:1967 the role 1960:1967 the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity 1960:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 11 33 theme cell 1797:1800 arg1 damage 1802:1807 tubular cell damage 1789:1807 tubular cell damage 1789:1807 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 2 34 theme cultivated 373:382 arg1 alternative 474:484 an alternative 471:484 an alternative to scarce sources of CC 471:508 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 2 34 theme cultivated 373:382 arg1 mycelia 384:390 artificially cultivated mycelia 360:390 artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) 360:437 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 5 35 from day 877:879 arg1 end 857:859 the end 853:859 the end of the study on day 8 853:881 At the end of the study on day 8, all rats were sacrificed, and the blood and kidneys retrieved. 36614214 0 36 theme Nephrotoxicity 45:58 arg1 Amelioration 0:11 Amelioration 0:11 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 0:178 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 36614214 7 37 theme regulated 1110:1118 arg1 protein 1120:1126 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 1052:1129 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) 1052:1138 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 7 37 theme regulated 1110:1118 arg1 GRP 1132:1134 GRP 78 1132:1137 GRP 78 1132:1137 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 4 38 theme male 677:680 arg1 rats 697:700 male Sprague-Dawley rats 677:700 male Sprague-Dawley rats 677:700 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 1 39 theme therapeutic 251:261 arg1 effect 263:268 a therapeutic effect 249:268 a therapeutic effect 249:268 Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. 36614214 11 40 contain has 1679:1681 arg1 CCM 1675:1677 CCM 1675:1677 CCM 1675:1677 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 11 40 contain has 1679:1681 arg2 potential 1687:1695 the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2 1683:1901 the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2 1683:1901 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 7 41 theme chaperone 1092:1100 arg1 protein 1120:1126 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 1052:1129 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) 1052:1138 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 7 41 theme chaperone 1092:1100 arg1 GRP 1132:1134 GRP 78 1132:1137 GRP 78 1132:1137 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 12 42 from nephrotoxicity 2107:2120 arg1 system 2060:2065 the defense system 2048:2065 the defense system of renal functions in CsA-induced acute nephrotoxicity 2048:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 2 43 theme liquid 408:413 arg1 cultivation 415:425 submerged liquid cultivation 398:425 submerged liquid cultivation of CC (CCM) 398:437 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 0 44 theme Cyclosporine 16:27 arg1 Nephrotoxicity 45:58 Cyclosporine A-Induced Acute Nephrotoxicity 16:58 Cyclosporine A-Induced Acute Nephrotoxicity 16:58 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 36614214 7 45 theme acute 1182:1186 arg1 nephrotoxicity 1188:1201 acute nephrotoxicity 1182:1201 acute nephrotoxicity 1182:1201 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 9 46 theme hematoxylin 1327:1337 arg1 tissues 1364:1370 hematoxylin and eosin stained kidney tissues 1327:1370 hematoxylin and eosin stained kidney tissues 1327:1370 Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. 36614214 0 47 theme Acute 39:43 arg1 Nephrotoxicity 45:58 Cyclosporine A-Induced Acute Nephrotoxicity 16:58 Cyclosporine A-Induced Acute Nephrotoxicity 16:58 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 36614214 1 48 theme kidney 281:286 arg1 disease 288:294 chronic kidney disease 273:294 chronic kidney disease 273:294 Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. 36614214 9 49 theme eosin 1343:1347 arg1 tissues 1364:1370 hematoxylin and eosin stained kidney tissues 1327:1370 hematoxylin and eosin stained kidney tissues 1327:1370 Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. 36614214 0 50 theme cicadae 73:79 arg1 Mycelia 81:87 Cordyceps cicadae Mycelia 63:87 Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro 63:177 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 36614214 12 51 from functions 2076:2084 arg1 nephrotoxicity 2107:2120 CsA-induced acute nephrotoxicity 2089:2120 CsA-induced acute nephrotoxicity 2089:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 9 52 theme kidney 1357:1362 arg1 tissues 1364:1370 hematoxylin and eosin stained kidney tissues 1327:1370 hematoxylin and eosin stained kidney tissues 1327:1370 Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. 36614214 7 53 theme endoplasmic 1056:1066 arg1 ER 1079:1080 ER 1079:1080 ER 1079:1080 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 7 53 theme endoplasmic 1056:1066 arg1 reticulum 1068:1076 the endoplasmic reticulum 1052:1076 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) 1052:1138 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 3 54 theme CCM 578:580 arg1 effects 567:573 potential protective effects 546:573 potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity 546:638 However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. 36614214 12 55 from role 1964:1967 arg1 system 2060:2065 the defense system 2048:2065 the defense system of renal functions in CsA-induced acute nephrotoxicity 2048:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 11 56 theme CsA-induced 1727:1737 arg1 nephrotoxicity 1739:1752 CsA-induced nephrotoxicity 1727:1752 CsA-induced nephrotoxicity 1727:1752 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 3 57 theme acute 619:623 arg1 nephrotoxicity 625:638 cyclosporine A (CsA)-induced acute nephrotoxicity 590:638 cyclosporine A (CsA)-induced acute nephrotoxicity 590:638 However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. 36614214 2 58 theme natural 342:348 arg1 habitats 350:357 natural habitats 342:357 natural habitats 342:357 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 5 59 from end 857:859 arg1 day 877:879 day 8 877:881 day 8 877:881 At the end of the study on day 8, all rats were sacrificed, and the blood and kidneys retrieved. 36614214 12 60 theme defense 2052:2058 arg1 system 2060:2065 the defense system 2048:2065 the defense system of renal functions in CsA-induced acute nephrotoxicity 2048:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 11 61 theme tubular 1789:1795 arg1 damage 1802:1807 tubular cell damage 1789:1807 tubular cell damage 1789:1807 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 9 62 theme CCM 1412:1414 arg1 treatment 1399:1407 the combined treatment 1386:1407 the combined treatment of CCM 1386:1414 Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. 36614214 10 63 theme protein 1521:1527 arg1 expression 1529:1538 protein expression 1521:1538 protein expression 1521:1538 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 6 64 theme CsA-induced 947:957 arg1 nephrotoxicity 965:978 CsA-induced acute nephrotoxicity 947:978 CsA-induced acute nephrotoxicity 947:978 CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). 36614214 10 65 theme proteins 1565:1572 arg1 down-regulation 1502:1516 CsA-induced down-regulation 1490:1516 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 1490:1624 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 1 66 theme Fruiting 180:187 arg1 bodies 189:194 Fruiting bodies 180:194 Fruiting bodies of Cordyceps cicadae (CC) 180:220 Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. 36614214 12 67 theme renal 2070:2074 arg1 functions 2076:2084 renal functions 2070:2084 renal functions in CsA-induced acute nephrotoxicity 2070:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 9 68 from vacuolization 1434:1446 arg1 tubules 1457:1463 renal tubules 1451:1463 renal tubules 1451:1463 Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. 36614214 0 69 theme GRP78-IRE1-CHOP 133:147 arg1 Pathway 149:155 GRP78-IRE1-CHOP Pathway 133:155 GRP78-IRE1-CHOP Pathway 133:155 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 36614214 10 70 theme ion 1553:1555 arg1 proteins 1565:1572 magnesium ion channel proteins 1543:1572 magnesium ion channel proteins 1543:1572 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 11 71 theme ER 1814:1815 arg1 stress 1817:1822 ER stress 1814:1822 ER stress 1814:1822 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 4 72 theme oral 791:794 arg1 mg/kg 784:788 10 mg/kg 781:788 10 mg/kg 781:788 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 4 72 theme oral 791:794 arg1 gavage 796:801 oral gavage 791:801 oral gavage 791:801 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 4 73 dep CsA 809:811 arg1 mg 823:824 40 mg and 400 mg/kg 820:838 mg 823:824 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 4 73 dep CsA 809:811 arg1 mg/kg 834:838 40 mg and 400 mg/kg 820:838 mg/kg 834:838 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 3 74 theme protective 556:565 arg1 effects 567:573 potential protective effects 546:573 potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity 546:638 However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. 36614214 1 75 theme cicadae 209:215 arg1 bodies 189:194 Fruiting bodies 180:194 Fruiting bodies of Cordyceps cicadae (CC) 180:220 Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. 36614214 9 76 theme CsA-induced 1470:1480 arg1 damage 1482:1487 CsA-induced damage 1470:1487 CsA-induced damage 1470:1487 Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. 36614214 6 77 theme urea 1021:1024 arg1 BUN 1036:1038 BUN 1036:1038 BUN 1036:1038 CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). 36614214 6 77 theme urea 1021:1024 arg1 nitrogen 1026:1033 blood urea nitrogen 1015:1033 blood urea nitrogen (BUN) 1015:1039 CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). 36614214 12 78 from system 2060:2065 arg1 understanding 1943:1955 the in-depth understanding 1930:1955 the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity 1930:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 12 78 from system 2060:2065 arg1 nephrotoxicity 2107:2120 CsA-induced acute nephrotoxicity 2089:2120 CsA-induced acute nephrotoxicity 2089:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 10 79 theme transient 1578:1586 arg1 melastatin 1607:1616 transient receptor potential melastatin 1578:1616 transient receptor potential melastatin 1578:1616 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 11 80 theme tubular 1869:1875 arg1 HK-2 1898:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 7 81 with rats 1172:1175 arg1 nephrotoxicity 1188:1201 acute nephrotoxicity 1182:1201 acute nephrotoxicity 1182:1201 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 11 82 theme magnesium 1766:1774 arg1 wasting 1780:1786 magnesium ion wasting 1766:1786 magnesium ion wasting 1766:1786 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 11 83 theme renal 1854:1858 arg1 HK-2 1898:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 human renal proximal tubular epithelial cell line HK-2 1848:1901 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 8 84 theme synchronous 1253:1263 arg1 CCM 1280:1282 CCM 1280:1282 CCM (40 or 400 mg/kg) 1280:1300 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 84 theme synchronous 1253:1263 arg1 mg/kg 1295:1299 40 or 400 mg/kg 1285:1299 40 or 400 mg/kg 1285:1299 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 84 theme synchronous 1253:1263 arg1 CsA 1307:1309 CsA 1307:1309 CsA 1307:1309 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 84 theme synchronous 1253:1263 arg1 groups 1270:1275 synchronous oral groups 1253:1275 synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA 1253:1309 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 6 85 theme increased 995:1003 arg1 levels 1005:1010 increased levels 995:1010 increased levels of blood urea nitrogen (BUN) 995:1039 CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). 36614214 5 86 theme study 868:872 arg1 end 857:859 the end 853:859 the end of the study on day 8 853:881 At the end of the study on day 8, all rats were sacrificed, and the blood and kidneys retrieved. 36614214 0 87 theme Mg+2 93:96 arg1 Reabsorption 98:109 Mg+2 Reabsorption 93:109 Mg+2 Reabsorption 93:109 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 36614214 8 88 theme CCM 1280:1282 arg1 CCM 1280:1282 CCM 1280:1282 CCM (40 or 400 mg/kg) 1280:1300 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 88 theme CCM 1280:1282 arg1 mg/kg 1295:1299 40 or 400 mg/kg 1285:1299 40 or 400 mg/kg 1285:1299 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 88 theme CCM 1280:1282 arg1 CsA 1307:1309 CsA 1307:1309 CsA 1307:1309 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 88 theme CCM 1280:1282 arg1 groups 1270:1275 synchronous oral groups 1253:1275 synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA 1253:1309 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 2 89 theme scarce 489:494 arg1 sources 496:502 scarce sources 489:502 scarce sources of CC 489:508 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 12 90 theme CCM 2041:2043 arg1 metabolites 2026:2036 the main secondary metabolites 2007:2036 the main secondary metabolites of CCM 2007:2043 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 7 91 theme glucose 1102:1108 arg1 protein 1120:1126 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 1052:1129 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) 1052:1138 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 7 91 theme glucose 1102:1108 arg1 GRP 1132:1134 GRP 78 1132:1137 GRP 78 1132:1137 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 12 92 theme secondary 2016:2024 arg1 metabolites 2026:2036 the main secondary metabolites 2007:2036 the main secondary metabolites of CCM 2007:2043 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 7 93 theme resident 1083:1090 arg1 protein 1120:1126 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 1052:1129 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) 1052:1138 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 7 93 theme resident 1083:1090 arg1 GRP 1132:1134 GRP 78 1132:1137 GRP 78 1132:1137 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 2 94 theme CC 430:431 arg1 cultivation 415:425 submerged liquid cultivation 398:425 submerged liquid cultivation of CC (CCM) 398:437 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 10 95 theme combined 1648:1655 arg1 treatment 1657:1665 the combined treatment 1644:1665 the combined treatment of CCM 1644:1672 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 12 96 theme polysaccharides 1972:1986 arg1 role 1964:1967 the role 1960:1967 the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity 1960:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 0 97 theme A-Induced 29:37 arg1 Nephrotoxicity 45:58 Cyclosporine A-Induced Acute Nephrotoxicity 16:58 Cyclosporine A-Induced Acute Nephrotoxicity 16:58 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 36614214 10 98 theme potential 1597:1605 arg1 melastatin 1607:1616 transient receptor potential melastatin 1578:1616 transient receptor potential melastatin 1578:1616 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 8 99 theme CsA 1307:1309 arg1 CCM 1280:1282 CCM 1280:1282 CCM (40 or 400 mg/kg) 1280:1300 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 99 theme CsA 1307:1309 arg1 mg/kg 1295:1299 40 or 400 mg/kg 1285:1299 40 or 400 mg/kg 1285:1299 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 99 theme CsA 1307:1309 arg1 CsA 1307:1309 CsA 1307:1309 CsA 1307:1309 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 8 99 theme CsA 1307:1309 arg1 groups 1270:1275 synchronous oral groups 1253:1275 synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA 1253:1309 BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. 36614214 4 100 theme Sprague-Dawley 682:695 arg1 rats 697:700 male Sprague-Dawley rats 677:700 male Sprague-Dawley rats 677:700 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 2 101 theme submerged 398:406 arg1 cultivation 415:425 submerged liquid cultivation 398:425 submerged liquid cultivation of CC (CCM) 398:437 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 4 102 dep CsA 776:778 arg1 mg/kg 784:788 10 mg/kg 781:788 10 mg/kg 781:788 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 4 102 dep CsA 776:778 arg1 gavage 796:801 oral gavage 791:801 oral gavage 791:801 In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). 36614214 1 103 theme chronic 273:279 arg1 disease 288:294 chronic kidney disease 273:294 chronic kidney disease 273:294 Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. 36614214 7 104 theme reticulum 1068:1076 arg1 protein 1120:1126 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 1052:1129 the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) 1052:1138 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 7 104 theme reticulum 1068:1076 arg1 GRP 1132:1134 GRP 78 1132:1137 GRP 78 1132:1137 Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. 36614214 0 105 theme Cordyceps 63:71 arg1 Mycelia 81:87 Cordyceps cicadae Mycelia 63:87 Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro 63:177 Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro. 36614214 9 106 theme stained 1349:1355 arg1 tissues 1364:1370 hematoxylin and eosin stained kidney tissues 1327:1370 hematoxylin and eosin stained kidney tissues 1327:1370 Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. 36614214 2 107 from habitats 350:357 arg1 resources 327:335 the rare and expensive resources 304:335 the rare and expensive resources from natural habitats 304:357 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 10 108 theme CCM 1670:1672 arg1 treatment 1657:1665 the combined treatment 1644:1665 the combined treatment of CCM 1644:1672 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 12 109 theme role 1964:1967 arg1 understanding 1943:1955 the in-depth understanding 1930:1955 the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity 1930:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 2 110 theme rare 308:311 arg1 resources 327:335 the rare and expensive resources 304:335 the rare and expensive resources from natural habitats 304:357 Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. 36614214 9 111 theme tissues 1364:1370 arg1 Examination 1312:1322 Examination 1312:1322 Examination of hematoxylin and eosin stained kidney tissues 1312:1370 Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. 36614214 3 112 theme -induced 610:617 arg1 nephrotoxicity 625:638 cyclosporine A (CsA)-induced acute nephrotoxicity 590:638 cyclosporine A (CsA)-induced acute nephrotoxicity 590:638 However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. 36614214 11 113 theme ion 1776:1778 arg1 wasting 1780:1786 magnesium ion wasting 1766:1786 magnesium ion wasting 1766:1786 CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. 36614214 12 114 theme in-depth 1934:1941 arg1 understanding 1943:1955 the in-depth understanding 1930:1955 the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity 1930:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36614214 10 115 theme CsA-induced 1490:1500 arg1 down-regulation 1502:1516 CsA-induced down-regulation 1490:1516 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 1490:1624 CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. 36614214 12 116 from understanding 1943:1955 arg1 system 2060:2065 the defense system 2048:2065 the defense system of renal functions in CsA-induced acute nephrotoxicity 2048:2120 Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. 36477252 6 0 theme cell 919:922 arg1 signalling 932:941 cell surface signalling 919:941 cell surface signalling 919:941 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 5 1 theme E. 641:642 arg1 gracilis 644:651 E. gracilis 641:651 E. gracilis 641:651 It was recently shown that E. gracilis possesses the machinery for producing a range of protein glycosylations and make simple N-glycans, but the modified proteins were not identified. 36477252 6 2 theme cellular 878:885 arg1 proteases 887:895 extra cellular proteases 872:895 extra cellular proteases 872:895 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 0 3 theme proteomic 64:72 arg1 approach 74:81 a proteomic approach 62:81 a proteomic approach 62:81 Glycosylated proteins in the protozoan alga Euglena gracilis: a proteomic approach. 36477252 0 4 from proteins 13:20 arg1 gracilis 52:59 the protozoan alga Euglena gracilis 25:59 the protozoan alga Euglena gracilis 25:59 Glycosylated proteins in the protozoan alga Euglena gracilis: a proteomic approach. 36477252 3 5 theme nutritional 489:499 arg1 supplements 501:511 nutritional supplements 489:511 nutritional supplements 489:511 Euglena gracilis is an industrially important microalga, used in the production of biofuels and nutritional supplements. 36477252 7 6 theme important 1095:1103 arg1 functions 1111:1119 important novel functions 1095:1119 important novel functions in Euglena 1095:1130 Notably, many of the most highly expressed and glycosylated proteins are not related to any known sequences and are therefore likely to be involved in important novel functions in Euglena. 36477252 7 7 theme expressed 977:985 arg1 proteins 1004:1011 the most highly expressed and glycosylated proteins 961:1011 the most highly expressed and glycosylated proteins 961:1011 Notably, many of the most highly expressed and glycosylated proteins are not related to any known sequences and are therefore likely to be involved in important novel functions in Euglena. 36477252 7 8 theme novel 1105:1109 arg1 functions 1111:1119 important novel functions 1095:1119 important novel functions in Euglena 1095:1130 Notably, many of the most highly expressed and glycosylated proteins are not related to any known sequences and are therefore likely to be involved in important novel functions in Euglena. 36477252 2 9 theme little 247:252 arg1 research 254:261 little research 247:261 little research 247:261 However, little research has been conducted to investigate the conservation and variation of protein glycosylation pathways in other eukaryotic organisms. 36477252 5 10 theme simple 734:739 arg1 N-glycans 741:749 simple N-glycans 734:749 simple N-glycans 734:749 It was recently shown that E. gracilis possesses the machinery for producing a range of protein glycosylations and make simple N-glycans, but the modified proteins were not identified. 36477252 2 11 from conservation 301:312 arg1 organisms 382:390 other eukaryotic organisms 365:390 other eukaryotic organisms 365:390 However, little research has been conducted to investigate the conservation and variation of protein glycosylation pathways in other eukaryotic organisms. 36477252 2 12 theme eukaryotic 371:380 arg1 organisms 382:390 other eukaryotic organisms 365:390 other eukaryotic organisms 365:390 However, little research has been conducted to investigate the conservation and variation of protein glycosylation pathways in other eukaryotic organisms. 36477252 1 13 gly glycosylation 92:104 arg1 parasites 227:235 parasites 227:235 parasites 227:235 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 13 gly glycosylation 92:104 arg1 cells 217:221 mammalian cells 207:221 mammalian cells 207:221 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 3 14 theme Euglena 393:399 arg1 microalga 439:447 an industrially important microalga 413:447 an industrially important microalga 413:447 Euglena gracilis is an industrially important microalga, used in the production of biofuels and nutritional supplements. 36477252 3 14 theme Euglena 393:399 arg1 gracilis 401:408 Euglena gracilis 393:408 Euglena gracilis 393:408 Euglena gracilis is an industrially important microalga, used in the production of biofuels and nutritional supplements. 36477252 5 15 contain possesses 653:661 arg1 gracilis 644:651 E. gracilis 641:651 E. gracilis 641:651 It was recently shown that E. gracilis possesses the machinery for producing a range of protein glycosylations and make simple N-glycans, but the modified proteins were not identified. 36477252 5 15 contain possesses 653:661 arg2 machinery 667:675 the machinery 663:675 the machinery for producing a range of protein glycosylations and make simple N-glycans 663:749 It was recently shown that E. gracilis possesses the machinery for producing a range of protein glycosylations and make simple N-glycans, but the modified proteins were not identified. 36477252 2 16 theme other 365:369 arg1 organisms 382:390 other eukaryotic organisms 365:390 other eukaryotic organisms 365:390 However, little research has been conducted to investigate the conservation and variation of protein glycosylation pathways in other eukaryotic organisms. 36477252 4 17 from algae 563:567 arg1 divergent 542:550 divergent 542:550 divergent 542:550 It is evolutionarily highly divergent from green algae and more related to Kinetoplastid pathogens. 36477252 5 18 theme modified 760:767 arg1 proteins 769:776 the modified proteins 756:776 the modified proteins 756:776 It was recently shown that E. gracilis possesses the machinery for producing a range of protein glycosylations and make simple N-glycans, but the modified proteins were not identified. 36477252 2 19 from variation 318:326 arg1 organisms 382:390 other eukaryotic organisms 365:390 other eukaryotic organisms 365:390 However, little research has been conducted to investigate the conservation and variation of protein glycosylation pathways in other eukaryotic organisms. 36477252 0 20 dep approach 74:81 arg1 proteins 13:20 Glycosylated proteins 0:20 Glycosylated proteins in the protozoan alga Euglena gracilis 0:59 Glycosylated proteins in the protozoan alga Euglena gracilis: a proteomic approach. 36477252 6 21 gly glycosylated 825:836 arg1 proteins 838:845 the glycosylated proteins 821:845 the glycosylated proteins 821:845 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 6 21 gly glycosylated 825:836 arg1 transporters 858:869 transporters 858:869 transporters 858:869 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 6 21 gly glycosylated 825:836 arg1 those 901:905 those 901:905 those 901:905 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 6 21 gly glycosylated 825:836 arg1 proteases 887:895 extra cellular proteases 872:895 extra cellular proteases 872:895 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 0 22 theme Glycosylated 0:11 arg1 proteins 13:20 Glycosylated proteins 0:20 Glycosylated proteins in the protozoan alga Euglena gracilis 0:59 Glycosylated proteins in the protozoan alga Euglena gracilis: a proteomic approach. 36477252 7 23 gly glycosylated 991:1002 arg1 proteins 1004:1011 the most highly expressed and glycosylated proteins 961:1011 the most highly expressed and glycosylated proteins 961:1011 Notably, many of the most highly expressed and glycosylated proteins are not related to any known sequences and are therefore likely to be involved in important novel functions in Euglena. 36477252 1 24 theme Protein 84:90 arg1 hall 148:151 a hall mark 146:156 a hall mark of Eukaryotic cells 146:176 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 24 theme Protein 84:90 arg1 glycosylation 92:104 Protein glycosylation 84:104 Protein glycosylation 84:104 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 24 theme Protein 84:90 arg1 glycans 134:140 particular N-linked glycans 114:140 particular N-linked glycans 114:140 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 2 25 theme pathways 353:360 arg1 conservation 301:312 conservation 301:312 conservation 301:312 However, little research has been conducted to investigate the conservation and variation of protein glycosylation pathways in other eukaryotic organisms. 36477252 2 25 theme pathways 353:360 arg1 variation 318:326 variation 318:326 variation 318:326 However, little research has been conducted to investigate the conservation and variation of protein glycosylation pathways in other eukaryotic organisms. 36477252 1 26 theme cells 172:176 arg1 hall 148:151 a hall mark 146:156 a hall mark of Eukaryotic cells 146:176 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 26 theme cells 172:176 arg1 glycosylation 92:104 Protein glycosylation 84:104 Protein glycosylation 84:104 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 26 theme cells 172:176 arg1 glycans 134:140 particular N-linked glycans 114:140 particular N-linked glycans 114:140 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 6 27 theme extra 872:876 arg1 proteases 887:895 extra cellular proteases 872:895 extra cellular proteases 872:895 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 2 28 dep conservation 301:312 arg1 the 297:299 the 297:299 the 297:299 However, little research has been conducted to investigate the conservation and variation of protein glycosylation pathways in other eukaryotic organisms. 36477252 3 29 theme supplements 501:511 arg1 production 462:471 the production 458:471 the production of biofuels and nutritional supplements 458:511 Euglena gracilis is an industrially important microalga, used in the production of biofuels and nutritional supplements. 36477252 0 30 theme alga 39:42 arg1 gracilis 52:59 the protozoan alga Euglena gracilis 25:59 the protozoan alga Euglena gracilis 25:59 Glycosylated proteins in the protozoan alga Euglena gracilis: a proteomic approach. 36477252 4 31 theme green 557:561 arg1 algae 563:567 green algae 557:567 green algae 557:567 It is evolutionarily highly divergent from green algae and more related to Kinetoplastid pathogens. 36477252 5 32 theme protein 702:708 arg1 glycosylations 710:723 protein glycosylations 702:723 protein glycosylations 702:723 It was recently shown that E. gracilis possesses the machinery for producing a range of protein glycosylations and make simple N-glycans, but the modified proteins were not identified. 36477252 1 33 theme Eukaryotic 161:170 arg1 cells 172:176 Eukaryotic cells 161:176 Eukaryotic cells 161:176 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 0 34 theme protozoan 29:37 arg1 gracilis 52:59 the protozoan alga Euglena gracilis 25:59 the protozoan alga Euglena gracilis 25:59 Glycosylated proteins in the protozoan alga Euglena gracilis: a proteomic approach. 36477252 5 35 theme glycosylations 710:723 arg1 range 693:697 a range 691:697 a range of protein glycosylations 691:723 It was recently shown that E. gracilis possesses the machinery for producing a range of protein glycosylations and make simple N-glycans, but the modified proteins were not identified. 36477252 7 36 theme known 1036:1040 arg1 sequences 1042:1050 any known sequences 1032:1050 any known sequences 1032:1050 Notably, many of the most highly expressed and glycosylated proteins are not related to any known sequences and are therefore likely to be involved in important novel functions in Euglena. 36477252 1 37 dep hall 148:151 arg1 mark 153:156 mark 153:156 mark 153:156 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 0 38 theme Euglena 44:50 arg1 gracilis 52:59 the protozoan alga Euglena gracilis 25:59 the protozoan alga Euglena gracilis 25:59 Glycosylated proteins in the protozoan alga Euglena gracilis: a proteomic approach. 36477252 7 39 from functions 1111:1119 arg1 Euglena 1124:1130 Euglena 1124:1130 Euglena 1124:1130 Notably, many of the most highly expressed and glycosylated proteins are not related to any known sequences and are therefore likely to be involved in important novel functions in Euglena. 36477252 1 40 link N-linked 125:132 arg1 hall 148:151 a hall mark 146:156 a hall mark of Eukaryotic cells 146:176 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 40 link N-linked 125:132 arg1 glycosylation 92:104 Protein glycosylation 84:104 Protein glycosylation 84:104 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 40 link N-linked 125:132 arg1 glycans 134:140 particular N-linked glycans 114:140 particular N-linked glycans 114:140 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 7 41 theme proteins 1004:1011 arg1 proteins 1004:1011 the most highly expressed and glycosylated proteins 961:1011 the most highly expressed and glycosylated proteins 961:1011 Notably, many of the most highly expressed and glycosylated proteins are not related to any known sequences and are therefore likely to be involved in important novel functions in Euglena. 36477252 7 41 theme proteins 1004:1011 arg1 many 953:956 many 953:956 many 953:956 Notably, many of the most highly expressed and glycosylated proteins are not related to any known sequences and are therefore likely to be involved in important novel functions in Euglena. 36477252 3 42 theme biofuels 476:483 arg1 production 462:471 the production 458:471 the production of biofuels and nutritional supplements 458:511 Euglena gracilis is an industrially important microalga, used in the production of biofuels and nutritional supplements. 36477252 1 43 theme particular 114:123 arg1 hall 148:151 a hall mark 146:156 a hall mark of Eukaryotic cells 146:176 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 43 theme particular 114:123 arg1 glycosylation 92:104 Protein glycosylation 84:104 Protein glycosylation 84:104 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 43 theme particular 114:123 arg1 glycans 134:140 particular N-linked glycans 114:140 particular N-linked glycans 114:140 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 6 44 theme glycosylated 825:836 arg1 proteins 838:845 the glycosylated proteins 821:845 the glycosylated proteins 821:845 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 6 44 theme glycosylated 825:836 arg1 transporters 858:869 transporters 858:869 transporters 858:869 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 6 44 theme glycosylated 825:836 arg1 those 901:905 those 901:905 those 901:905 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 6 44 theme glycosylated 825:836 arg1 proteases 887:895 extra cellular proteases 872:895 extra cellular proteases 872:895 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 1 45 theme N-linked 125:132 arg1 hall 148:151 a hall mark 146:156 a hall mark of Eukaryotic cells 146:176 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 45 theme N-linked 125:132 arg1 glycosylation 92:104 Protein glycosylation 84:104 Protein glycosylation 84:104 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 1 45 theme N-linked 125:132 arg1 glycans 134:140 particular N-linked glycans 114:140 particular N-linked glycans 114:140 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36477252 4 46 theme Kinetoplastid 589:601 arg1 pathogens 603:611 Kinetoplastid pathogens 589:611 Kinetoplastid pathogens 589:611 It is evolutionarily highly divergent from green algae and more related to Kinetoplastid pathogens. 36477252 7 47 theme glycosylated 991:1002 arg1 proteins 1004:1011 the most highly expressed and glycosylated proteins 961:1011 the most highly expressed and glycosylated proteins 961:1011 Notably, many of the most highly expressed and glycosylated proteins are not related to any known sequences and are therefore likely to be involved in important novel functions in Euglena. 36477252 2 48 theme glycosylation 339:351 arg1 pathways 353:360 protein glycosylation pathways 331:360 protein glycosylation pathways 331:360 However, little research has been conducted to investigate the conservation and variation of protein glycosylation pathways in other eukaryotic organisms. 36477252 3 49 theme important 429:437 arg1 microalga 439:447 an industrially important microalga 413:447 an industrially important microalga 413:447 Euglena gracilis is an industrially important microalga, used in the production of biofuels and nutritional supplements. 36477252 3 49 theme important 429:437 arg1 gracilis 401:408 Euglena gracilis 393:408 Euglena gracilis 393:408 Euglena gracilis is an industrially important microalga, used in the production of biofuels and nutritional supplements. 36477252 6 50 theme surface 924:930 arg1 signalling 932:941 cell surface signalling 919:941 cell surface signalling 919:941 This study identifies the glycosylated proteins, including transporters, extra cellular proteases and those involved in cell surface signalling. 36477252 2 51 theme protein 331:337 arg1 pathways 353:360 protein glycosylation pathways 331:360 protein glycosylation pathways 331:360 However, little research has been conducted to investigate the conservation and variation of protein glycosylation pathways in other eukaryotic organisms. 36477252 1 52 theme mammalian 207:215 arg1 cells 217:221 mammalian cells 207:221 mammalian cells 207:221 Protein glycosylation, and in particular N-linked glycans, is a hall mark of Eukaryotic cells and has been well studied in mammalian cells and parasites. 36597530 6 0 theme SARS-CoV 837:844 arg1 2003 846:849 SARS-CoV 2003 837:849 all tested variants of concern as well as SARS-CoV 2003 795:849 Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors. 36597530 4 1 theme potent 471:476 arg1 inhibitor 478:486 a potent inhibitor 469:486 a potent inhibitor of SARS-CoV-2 viral entry 469:512 Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. 36597530 5 2 theme soluble 682:688 arg1 aggregates 690:699 soluble aggregates 682:699 soluble aggregates 682:699 Using a variety of biophysical tools, we demonstrate that the interaction is avidity driven and that BOA crosslinks the Spike protein into soluble aggregates. 36597530 5 3 theme biophysical 562:572 arg1 tools 574:578 biophysical tools 562:578 biophysical tools 562:578 Using a variety of biophysical tools, we demonstrate that the interaction is avidity driven and that BOA crosslinks the Spike protein into soluble aggregates. 36597530 5 4 theme tools 574:578 arg1 variety 551:557 a variety 549:557 a variety of biophysical tools 549:578 Using a variety of biophysical tools, we demonstrate that the interaction is avidity driven and that BOA crosslinks the Spike protein into soluble aggregates. 36597530 5 4 theme tools 574:578 arg1 tools 574:578 biophysical tools 562:578 biophysical tools 562:578 Using a variety of biophysical tools, we demonstrate that the interaction is avidity driven and that BOA crosslinks the Spike protein into soluble aggregates. 36597530 1 5 theme SARS-CoV-2 58:67 arg1 Spike 69:73 SARS-CoV-2 Spike 58:73 SARS-CoV-2 Spike 58:73 SARS-CoV-2 Spike harbors glycans which function as ligands for lectins. 36597530 3 6 theme antiviral 320:328 arg1 lectin 330:335 an antiviral lectin 317:335 an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans 317:409 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 3 6 theme antiviral 320:328 arg1 agglutinin 297:306 Burkholderia oklahomensis agglutinin 271:306 Burkholderia oklahomensis agglutinin (BOA) 271:312 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 2 7 theme Spike 256:260 arg1 protein 262:268 the Spike protein 252:268 the Spike protein 252:268 Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the Spike protein. 36597530 0 8 theme Viral 45:49 arg1 Entry 51:55 SARS-CoV2 Viral Entry 35:55 SARS-CoV2 Viral Entry 35:55 Targeting Spike Glycans to Inhibit SARS-CoV2 Viral Entry. 36597530 3 9 gly glycoproteins 363:375 arg1 glycoproteins 363:375 viral glycoproteins 357:375 viral glycoproteins 357:375 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 0 10 theme Spike 10:14 arg1 Glycans 16:22 Spike Glycans 10:22 Spike Glycans 10:22 Targeting Spike Glycans to Inhibit SARS-CoV2 Viral Entry. 36597530 4 11 theme Spike 448:452 arg1 protein 454:460 the Spike protein 444:460 the Spike protein 444:460 Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. 36597530 6 12 theme glycan-targeting 870:885 arg1 molecules 887:895 glycan-targeting molecules 870:895 glycan-targeting molecules 870:895 Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors. 36597530 6 13 theme pan-coronavirus 922:936 arg1 inhibitors 938:947 pan-coronavirus inhibitors 922:947 pan-coronavirus inhibitors 922:947 Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors. 36597530 6 14 contain have 897:900 arg1 molecules 887:895 glycan-targeting molecules 870:895 glycan-targeting molecules 870:895 Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors. 36597530 6 14 contain have 897:900 arg2 potential 906:914 the potential to be pan-coronavirus inhibitors 902:947 the potential to be pan-coronavirus inhibitors 902:947 Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors. 36597530 4 15 theme entry 508:512 arg1 inhibitor 478:486 a potent inhibitor 469:486 a potent inhibitor of SARS-CoV-2 viral entry 469:512 Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. 36597530 3 16 theme viral 357:361 arg1 glycoproteins 363:375 viral glycoproteins 357:375 viral glycoproteins 357:375 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 5 17 theme Spike 663:667 arg1 protein 669:675 the Spike protein 659:675 the Spike protein into soluble aggregates 659:699 Using a variety of biophysical tools, we demonstrate that the interaction is avidity driven and that BOA crosslinks the Spike protein into soluble aggregates. 36597530 0 18 theme SARS-CoV2 35:43 arg1 Entry 51:55 SARS-CoV2 Viral Entry 35:55 SARS-CoV2 Viral Entry 35:55 Targeting Spike Glycans to Inhibit SARS-CoV2 Viral Entry. 36597530 4 19 theme nanomolar 517:525 arg1 concentrations 527:540 nanomolar concentrations 517:540 nanomolar concentrations 517:540 Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. 36597530 3 20 link N-linked 381:388 arg1 glycans 403:409 N-linked high mannose glycans 381:409 N-linked high mannose glycans 381:409 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 2 21 from glycans 241:247 arg1 protein 262:268 the Spike protein 252:268 the Spike protein 252:268 Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the Spike protein. 36597530 2 22 theme cellular 215:222 arg1 entry 224:228 cellular entry 215:228 cellular entry 215:228 Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the Spike protein. 36597530 6 23 theme neutralization 727:740 arg1 assays 742:747 virus neutralization assays 721:747 virus neutralization assays 721:747 Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors. 36597530 3 24 theme N-linked 381:388 arg1 glycans 403:409 N-linked high mannose glycans 381:409 N-linked high mannose glycans 381:409 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 6 25 theme concern 818:824 arg1 variants 806:813 all tested variants 795:813 all tested variants of concern as well as SARS-CoV 2003 795:849 Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors. 36597530 6 25 theme concern 818:824 arg1 2003 846:849 SARS-CoV 2003 837:849 all tested variants of concern as well as SARS-CoV 2003 795:849 Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors. 36597530 6 26 theme virus 721:725 arg1 assays 742:747 virus neutralization assays 721:747 virus neutralization assays 721:747 Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors. 36597530 3 27 theme high 390:393 arg1 glycans 403:409 N-linked high mannose glycans 381:409 N-linked high mannose glycans 381:409 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 4 28 theme viral 502:506 arg1 entry 508:512 SARS-CoV-2 viral entry 491:512 SARS-CoV-2 viral entry 491:512 Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. 36597530 3 29 theme mannose 395:401 arg1 glycans 403:409 N-linked high mannose glycans 381:409 N-linked high mannose glycans 381:409 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 4 30 theme SARS-CoV-2 491:500 arg1 entry 508:512 SARS-CoV-2 viral entry 491:512 SARS-CoV-2 viral entry 491:512 Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. 36597530 3 31 theme Burkholderia 271:282 arg1 lectin 330:335 an antiviral lectin 317:335 an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans 317:409 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 3 31 theme Burkholderia 271:282 arg1 BOA 309:311 BOA 309:311 BOA 309:311 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 3 31 theme Burkholderia 271:282 arg1 agglutinin 297:306 Burkholderia oklahomensis agglutinin 271:306 Burkholderia oklahomensis agglutinin (BOA) 271:312 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 3 32 theme oklahomensis 284:295 arg1 lectin 330:335 an antiviral lectin 317:335 an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans 317:409 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 3 32 theme oklahomensis 284:295 arg1 BOA 309:311 BOA 309:311 BOA 309:311 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 3 32 theme oklahomensis 284:295 arg1 agglutinin 297:306 Burkholderia oklahomensis agglutinin 271:306 Burkholderia oklahomensis agglutinin (BOA) 271:312 Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. 36597530 6 33 theme tested 799:804 arg1 variants 806:813 all tested variants 795:813 all tested variants of concern as well as SARS-CoV 2003 795:849 Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors. 36597530 4 34 from concentrations 527:540 arg1 inhibitor 478:486 a potent inhibitor 469:486 a potent inhibitor of SARS-CoV-2 viral entry 469:512 Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. 34911160 0 0 theme Sugars 104:109 arg1 S-Glycosylation 67:81 Aqueous S-Glycosylation 59:81 Aqueous S-Glycosylation of Diverse Deoxythio Sugars 59:109 Streamlined Iterative Assembly of Thio-Oligosaccharides by Aqueous S-Glycosylation of Diverse Deoxythio Sugars. 34911160 3 1 theme efficient 382:390 arg1 methods 401:407 efficient chemical methods 382:407 efficient chemical methods including our recently reported BTM-catalyzed site-selective acylation 382:478 These syntheses featured efficient chemical methods including our recently reported BTM-catalyzed site-selective acylation. 34911160 5 2 theme high 750:753 arg1 chemo- 755:760 high chemo- 750:760 high chemo- 750:760 The aqueous glycosylation reaction proceeded smoothly to afford the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity. 34911160 4 3 theme -promoted 547:555 arg1 S-glycosylation 579:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation 535:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature 535:622 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 1 4 theme aqueous 187:193 arg1 glycosylation 195:207 aqueous glycosylation 187:207 aqueous glycosylation 187:207 A streamlined iterative assembly of thio-oligosaccharides was developed by aqueous glycosylation. 34911160 0 5 theme Deoxythio 94:102 arg1 Sugars 104:109 Diverse Deoxythio Sugars 86:109 Diverse Deoxythio Sugars 86:109 Streamlined Iterative Assembly of Thio-Oligosaccharides by Aqueous S-Glycosylation of Diverse Deoxythio Sugars. 34911160 4 6 theme deoxythio 495:503 arg1 sugars 505:510 The resulting deoxythio sugars 481:510 The resulting deoxythio sugars 481:510 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 3 7 theme reported 432:439 arg1 acylation 470:478 our recently reported BTM-catalyzed site-selective acylation 419:478 our recently reported BTM-catalyzed site-selective acylation 419:478 These syntheses featured efficient chemical methods including our recently reported BTM-catalyzed site-selective acylation. 34911160 4 8 from S-glycosylation 579:593 arg1 water 598:602 water 598:602 water 598:602 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 4 9 theme resulting 485:493 arg1 sugars 505:510 The resulting deoxythio sugars 481:510 The resulting deoxythio sugars 481:510 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 3 10 theme BTM-catalyzed 441:453 arg1 acylation 470:478 our recently reported BTM-catalyzed site-selective acylation 419:478 our recently reported BTM-catalyzed site-selective acylation 419:478 These syntheses featured efficient chemical methods including our recently reported BTM-catalyzed site-selective acylation. 34911160 5 11 theme 1,2-trans 707:715 arg1 S-glycosides 717:728 the corresponding 1,2-trans S-glycosides 689:728 the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity 689:782 The aqueous glycosylation reaction proceeded smoothly to afford the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity. 34911160 2 12 from sulfur 264:269 arg1 positions 284:292 different positions 274:292 different positions from commercially available starting materials 274:339 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials were described. 34911160 6 13 theme iterative 901:909 arg1 synthesis 911:919 iterative synthesis 901:919 iterative synthesis of thio-oligosaccharides 901:944 An appropriate choice of protecting groups for the thiol in the glycosyl donor was necessary for the development of iterative synthesis of thio-oligosaccharides. 34911160 4 14 gly S-glycosylation 579:593 arg1 temperature 612:622 room temperature 607:622 room temperature 607:622 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 4 14 gly S-glycosylation 579:593 arg2 temperature 612:622 room temperature 607:622 room temperature 607:622 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 4 14 gly S-glycosylation 579:593 arg1 water 598:602 water 598:602 water 598:602 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 6 15 theme appropriate 788:798 arg1 choice 800:805 An appropriate choice 785:805 An appropriate choice of protecting groups for the thiol in the glycosyl donor 785:862 An appropriate choice of protecting groups for the thiol in the glycosyl donor was necessary for the development of iterative synthesis of thio-oligosaccharides. 34911160 6 15 theme appropriate 788:798 arg1 necessary 868:876 necessary 868:876 necessary 868:876 An appropriate choice of protecting groups for the thiol in the glycosyl donor was necessary for the development of iterative synthesis of thio-oligosaccharides. 34911160 4 16 theme protecting 557:566 arg1 S-glycosylation 579:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation 535:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature 535:622 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 4 17 theme group-free 568:577 arg1 S-glycosylation 579:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation 535:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature 535:622 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 2 18 theme starting 322:329 arg1 materials 331:339 commercially available starting materials 299:339 commercially available starting materials 299:339 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials were described. 34911160 6 19 theme protecting 810:819 arg1 groups 821:826 protecting groups 810:826 protecting groups 810:826 An appropriate choice of protecting groups for the thiol in the glycosyl donor was necessary for the development of iterative synthesis of thio-oligosaccharides. 34911160 0 20 theme Iterative 12:20 arg1 Assembly 22:29 Iterative Assembly 12:29 Iterative Assembly of Thio-Oligosaccharides 12:54 Streamlined Iterative Assembly of Thio-Oligosaccharides by Aqueous S-Glycosylation of Diverse Deoxythio Sugars. 34911160 3 21 theme chemical 392:399 arg1 methods 401:407 efficient chemical methods 382:407 efficient chemical methods including our recently reported BTM-catalyzed site-selective acylation 382:478 These syntheses featured efficient chemical methods including our recently reported BTM-catalyzed site-selective acylation. 34911160 7 22 link N-linked 1035:1042 arg1 glycans 1044:1050 N-linked glycans core region 1035:1062 N-linked glycans core region 1035:1062 The aqueous glycosylation was then applied to the synthesis of a trimannoside moiety of N-linked glycans core region. 34911160 7 23 theme glycans 1044:1050 arg1 moiety 1025:1030 a trimannoside moiety 1010:1030 a trimannoside moiety of N-linked glycans core region 1010:1062 The aqueous glycosylation was then applied to the synthesis of a trimannoside moiety of N-linked glycans core region. 34911160 7 24 theme aqueous 951:957 arg1 glycosylation 959:971 The aqueous glycosylation 947:971 The aqueous glycosylation 947:971 The aqueous glycosylation was then applied to the synthesis of a trimannoside moiety of N-linked glycans core region. 34911160 3 25 theme site-selective 455:468 arg1 acylation 470:478 our recently reported BTM-catalyzed site-selective acylation 419:478 our recently reported BTM-catalyzed site-selective acylation 419:478 These syntheses featured efficient chemical methods including our recently reported BTM-catalyzed site-selective acylation. 34911160 7 26 theme core 1052:1055 arg1 region 1057:1062 core region 1052:1062 N-linked glycans core region 1035:1062 The aqueous glycosylation was then applied to the synthesis of a trimannoside moiety of N-linked glycans core region. 34911160 1 27 theme streamlined 114:124 arg1 assembly 136:143 A streamlined iterative assembly 112:143 A streamlined iterative assembly of thio-oligosaccharides 112:168 A streamlined iterative assembly of thio-oligosaccharides was developed by aqueous glycosylation. 34911160 6 28 theme thio-oligosaccharides 924:944 arg1 synthesis 911:919 iterative synthesis 901:919 iterative synthesis of thio-oligosaccharides 901:944 An appropriate choice of protecting groups for the thiol in the glycosyl donor was necessary for the development of iterative synthesis of thio-oligosaccharides. 34911160 4 29 theme Ca 539:540 arg1 S-glycosylation 579:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation 535:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature 535:622 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 1 30 theme iterative 126:134 arg1 assembly 136:143 A streamlined iterative assembly 112:143 A streamlined iterative assembly of thio-oligosaccharides 112:168 A streamlined iterative assembly of thio-oligosaccharides was developed by aqueous glycosylation. 34911160 6 31 theme groups 821:826 arg1 choice 800:805 An appropriate choice 785:805 An appropriate choice of protecting groups for the thiol in the glycosyl donor 785:862 An appropriate choice of protecting groups for the thiol in the glycosyl donor was necessary for the development of iterative synthesis of thio-oligosaccharides. 34911160 6 31 theme groups 821:826 arg1 necessary 868:876 necessary 868:876 necessary 868:876 An appropriate choice of protecting groups for the thiol in the glycosyl donor was necessary for the development of iterative synthesis of thio-oligosaccharides. 34911160 2 32 theme different 274:282 arg1 positions 284:292 different positions 274:292 different positions from commercially available starting materials 274:339 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials were described. 34911160 0 33 theme Thio-Oligosaccharides 34:54 arg1 Assembly 22:29 Iterative Assembly 12:29 Iterative Assembly of Thio-Oligosaccharides 12:54 Streamlined Iterative Assembly of Thio-Oligosaccharides by Aqueous S-Glycosylation of Diverse Deoxythio Sugars. 34911160 4 34 theme room 607:610 arg1 temperature 612:622 room temperature 607:622 room temperature 607:622 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 4 35 from temperature 612:622 arg1 S-glycosylation 579:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation 535:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature 535:622 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 2 36 theme Facile 210:215 arg1 syntheses 217:225 Facile syntheses 210:225 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials 210:339 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials were described. 34911160 4 37 used used 526:529 arg2 sugars 505:510 The resulting deoxythio sugars 481:510 The resulting deoxythio sugars 481:510 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 6 38 theme synthesis 911:919 arg1 development 886:896 the development 882:896 the development of iterative synthesis of thio-oligosaccharides 882:944 An appropriate choice of protecting groups for the thiol in the glycosyl donor was necessary for the development of iterative synthesis of thio-oligosaccharides. 34911160 5 39 theme aqueous 629:635 arg1 reaction 651:658 The aqueous glycosylation reaction 625:658 The aqueous glycosylation reaction 625:658 The aqueous glycosylation reaction proceeded smoothly to afford the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity. 34911160 5 40 with yields 738:743 arg1 chemo- 755:760 high chemo- 750:760 high chemo- 750:760 The aqueous glycosylation reaction proceeded smoothly to afford the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity. 34911160 5 40 with yields 738:743 arg1 stereoselectivity 766:782 stereoselectivity 766:782 stereoselectivity 766:782 The aqueous glycosylation reaction proceeded smoothly to afford the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity. 34911160 0 41 theme Aqueous 59:65 arg1 S-Glycosylation 67:81 Aqueous S-Glycosylation 59:81 Aqueous S-Glycosylation of Diverse Deoxythio Sugars 59:109 Streamlined Iterative Assembly of Thio-Oligosaccharides by Aqueous S-Glycosylation of Diverse Deoxythio Sugars. 34911160 5 42 theme good 733:736 arg1 yields 738:743 good yields 733:743 good yields with high chemo- and stereoselectivity 733:782 The aqueous glycosylation reaction proceeded smoothly to afford the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity. 34911160 5 43 theme glycosylation 637:649 arg1 reaction 651:658 The aqueous glycosylation reaction 625:658 The aqueous glycosylation reaction 625:658 The aqueous glycosylation reaction proceeded smoothly to afford the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity. 34911160 4 44 theme OH 542:543 arg1 S-glycosylation 579:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation 535:593 the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature 535:622 The resulting deoxythio sugars could then be used for the Ca(OH)2 -promoted protecting group-free S-glycosylation in water at room temperature. 34911160 2 45 from materials 331:339 arg1 positions 284:292 different positions 274:292 different positions from commercially available starting materials 274:339 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials were described. 34911160 2 46 theme sugars 248:253 arg1 syntheses 217:225 Facile syntheses 210:225 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials 210:339 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials were described. 34911160 2 47 theme available 312:320 arg1 materials 331:339 commercially available starting materials 299:339 commercially available starting materials 299:339 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials were described. 34911160 5 48 theme corresponding 693:705 arg1 S-glycosides 717:728 the corresponding 1,2-trans S-glycosides 689:728 the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity 689:782 The aqueous glycosylation reaction proceeded smoothly to afford the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity. 34911160 1 49 theme thio-oligosaccharides 148:168 arg1 assembly 136:143 A streamlined iterative assembly 112:143 A streamlined iterative assembly of thio-oligosaccharides 112:168 A streamlined iterative assembly of thio-oligosaccharides was developed by aqueous glycosylation. 34911160 7 50 theme N-linked 1035:1042 arg1 glycans 1044:1050 N-linked glycans core region 1035:1062 N-linked glycans core region 1035:1062 The aqueous glycosylation was then applied to the synthesis of a trimannoside moiety of N-linked glycans core region. 34911160 6 51 theme glycosyl 849:856 arg1 donor 858:862 the glycosyl donor 845:862 the glycosyl donor 845:862 An appropriate choice of protecting groups for the thiol in the glycosyl donor was necessary for the development of iterative synthesis of thio-oligosaccharides. 34911160 2 52 theme deoxythio 238:246 arg1 sugars 248:253 various deoxythio sugars 230:253 various deoxythio sugars 230:253 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials were described. 34911160 2 53 with syntheses 217:225 arg1 sulfur 264:269 the sulfur 260:269 the sulfur on different positions from commercially available starting materials 260:339 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials were described. 34911160 7 54 theme trimannoside 1012:1023 arg1 moiety 1025:1030 a trimannoside moiety 1010:1030 a trimannoside moiety of N-linked glycans core region 1010:1062 The aqueous glycosylation was then applied to the synthesis of a trimannoside moiety of N-linked glycans core region. 34911160 0 55 theme Diverse 86:92 arg1 Sugars 104:109 Diverse Deoxythio Sugars 86:109 Diverse Deoxythio Sugars 86:109 Streamlined Iterative Assembly of Thio-Oligosaccharides by Aqueous S-Glycosylation of Diverse Deoxythio Sugars. 34911160 2 56 theme various 230:236 arg1 sugars 248:253 various deoxythio sugars 230:253 various deoxythio sugars 230:253 Facile syntheses of various deoxythio sugars with the sulfur on different positions from commercially available starting materials were described. 34911160 6 57 from thiol 836:840 arg1 donor 858:862 the glycosyl donor 845:862 the glycosyl donor 845:862 An appropriate choice of protecting groups for the thiol in the glycosyl donor was necessary for the development of iterative synthesis of thio-oligosaccharides. 34911160 7 58 theme moiety 1025:1030 arg1 synthesis 997:1005 the synthesis 993:1005 the synthesis of a trimannoside moiety of N-linked glycans core region 993:1062 The aqueous glycosylation was then applied to the synthesis of a trimannoside moiety of N-linked glycans core region. 34911160 0 59 gly S-Glycosylation 67:81 arg1 Sugars 104:109 Diverse Deoxythio Sugars 86:109 Diverse Deoxythio Sugars 86:109 Streamlined Iterative Assembly of Thio-Oligosaccharides by Aqueous S-Glycosylation of Diverse Deoxythio Sugars. 34911160 5 60 from S-glycosides 717:728 arg1 yields 738:743 good yields 733:743 good yields with high chemo- and stereoselectivity 733:782 The aqueous glycosylation reaction proceeded smoothly to afford the corresponding 1,2-trans S-glycosides in good yields with high chemo- and stereoselectivity. 34911160 7 61 dep glycans 1044:1050 arg1 region 1057:1062 core region 1052:1062 N-linked glycans core region 1035:1062 The aqueous glycosylation was then applied to the synthesis of a trimannoside moiety of N-linked glycans core region. 37240010 5 0 from accumulation 817:828 arg1 bacteroids 860:869 bacteroids 860:869 bacteroids 860:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 1 from formation 792:800 arg1 bacteroids 860:869 bacteroids 860:869 bacteroids 860:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 1 2 theme Pisum 216:220 arg1 sativum 222:228 Pisum sativum 216:228 Pisum sativum L. 216:231 Triazole fungicides are widely used in agricultural production for plant protection, including pea (Pisum sativum L.). 37240010 5 3 dep changes 659:665 arg1 thinning 731:738 thinning 731:738 thinning 731:738 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 3 dep changes 659:665 arg1 clearing 718:725 their clearing 712:725 their clearing 712:725 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 3 dep changes 659:665 arg1 modifications 679:691 modifications 679:691 modifications in the cell walls (their clearing and thinning) 679:739 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 4 theme poly-β-hydroxybutyrates 833:855 arg1 formation 792:800 the formation 788:800 the formation of outgrowths 788:814 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 4 theme poly-β-hydroxybutyrates 833:855 arg1 fusion 914:919 fusion 914:919 fusion of symbiosomes 914:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 4 theme poly-β-hydroxybutyrates 833:855 arg1 accumulation 817:828 accumulation 817:828 accumulation of poly-β-hydroxybutyrates in bacteroids 817:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 4 theme poly-β-hydroxybutyrates 833:855 arg1 expansion 872:880 expansion 872:880 expansion of the peribacteroid space 872:907 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 8 5 from research 1412:1419 arg1 effects 1428:1434 the effects 1424:1434 the effects of pesticides on the legume-Rhizobium symbiosis in order to optimize their use 1424:1513 The data obtained indicate the need for further research on the effects of pesticides on the legume-Rhizobium symbiosis in order to optimize their use. 37240010 6 6 theme matrix 1129:1134 arg1 polysaccharides 1136:1150 matrix polysaccharides 1129:1150 matrix polysaccharides of cell walls 1129:1164 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 5 7 theme Transmission 587:598 arg1 microscopy 609:618 Transmission electron microscopy 587:618 Transmission electron microscopy 587:618 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 8 from poly-β-hydroxybutyrates 833:855 arg1 bacteroids 860:869 bacteroids 860:869 bacteroids 860:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 6 9 from decrease 1032:1039 arg1 activity 1048:1055 the activity 1044:1055 the activity of synthesis of cellulose microfibrils 1044:1094 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 6 9 from decrease 1032:1039 arg1 number 1119:1124 the number 1115:1124 the number of matrix polysaccharides of cell walls 1115:1164 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 0 10 theme Pea 74:76 arg1 Nodules 107:113 Pea (Pisum sativum L.) Symbiotic Nodules 74:113 Pea (Pisum sativum L.) Symbiotic Nodules 74:113 Effect of Triazole Fungicides Titul Duo and Vintage on the Development of Pea (Pisum sativum L.) Symbiotic Nodules. 37240010 0 10 theme Pea 74:76 arg1 Pisum 79:83 Pisum 79:83 Pisum 79:83 Effect of Triazole Fungicides Titul Duo and Vintage on the Development of Pea (Pisum sativum L.) Symbiotic Nodules. 37240010 0 11 from Vintage 44:50 arg1 Development 59:69 the Development 55:69 the Development of Pea (Pisum sativum L.) Symbiotic Nodules 55:113 Effect of Triazole Fungicides Titul Duo and Vintage on the Development of Pea (Pisum sativum L.) Symbiotic Nodules. 37240010 5 12 theme electron 600:607 arg1 microscopy 609:618 Transmission electron microscopy 587:618 Transmission electron microscopy 587:618 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 0 13 dep Pisum 79:83 arg1 L. 93:94 Pisum sativum L. 79:94 Pisum sativum L. 79:94 Effect of Triazole Fungicides Titul Duo and Vintage on the Development of Pea (Pisum sativum L.) Symbiotic Nodules. 37240010 6 14 from increase 1103:1110 arg1 activity 1048:1055 the activity 1044:1055 the activity of synthesis of cellulose microfibrils 1044:1094 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 6 14 from increase 1103:1110 arg1 number 1119:1124 the number 1115:1124 the number of matrix polysaccharides of cell walls 1115:1164 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 5 15 theme walls 777:781 arg1 thickening 742:751 thickening 742:751 thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes 742:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 15 theme walls 777:781 arg1 changes 659:665 the following ultrastructural changes 629:665 the following ultrastructural changes in nodules 629:676 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 8 16 theme pesticides 1439:1448 arg1 effects 1428:1434 the effects 1424:1434 the effects of pesticides on the legume-Rhizobium symbiosis in order to optimize their use 1424:1513 The data obtained indicate the need for further research on the effects of pesticides on the legume-Rhizobium symbiosis in order to optimize their use. 37240010 5 17 theme thread 770:775 arg1 walls 777:781 the infection thread walls 756:781 the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes 756:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 7 18 theme defense 1345:1351 arg1 reactions 1353:1361 defense reactions 1345:1361 defense reactions 1345:1361 The results obtained coincide well with the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions. 37240010 5 19 from changes 659:665 arg1 nodules 670:676 nodules 670:676 nodules 670:676 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 3 20 from effects 330:336 arg1 particular 411:420 particular 411:420 particular 411:420 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 3 20 from effects 330:336 arg1 morphology 433:442 nodule morphology 426:442 nodule morphology 426:442 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 3 20 from effects 330:336 arg1 formation 393:401 nodule formation 386:401 nodule formation 386:401 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 3 21 dep fungicides 350:359 arg1 fungicides 350:359 triazole fungicides Vintage and Titul Duo 341:381 triazole fungicides Vintage and Titul Duo 341:381 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 3 21 dep fungicides 350:359 arg1 Vintage 361:367 Vintage 361:367 Vintage 361:367 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 3 21 dep fungicides 350:359 arg1 Duo 379:381 Duo 379:381 Duo 379:381 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 8 22 from effects 1428:1434 arg1 symbiosis 1474:1482 the legume-Rhizobium symbiosis 1453:1482 the legume-Rhizobium symbiosis in order to optimize their use 1453:1513 The data obtained indicate the need for further research on the effects of pesticides on the legume-Rhizobium symbiosis in order to optimize their use. 37240010 3 23 theme nodule 386:391 arg1 formation 393:401 nodule formation 386:401 nodule formation 386:401 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 4 24 theme nodule 518:523 arg1 number 525:530 nodule number 518:530 nodule number 518:530 Both fungicides at the highest concentration decreased the nodule number and dry weight of the roots 20 days after inoculation. 37240010 5 25 from expansion 872:880 arg1 bacteroids 860:869 bacteroids 860:869 bacteroids 860:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 7 26 from increase 1262:1269 arg1 levels 1289:1294 the expression levels 1274:1294 the expression levels of genes that control cell wall modification and defense reactions 1274:1361 The results obtained coincide well with the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions. 37240010 6 27 theme walls 1012:1016 arg1 composition 992:1002 the composition 988:1002 the composition of cell walls 988:1016 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 4 28 from concentration 490:502 arg1 fungicides 464:473 Both fungicides 459:473 Both fungicides at the highest concentration 459:502 Both fungicides at the highest concentration decreased the nodule number and dry weight of the roots 20 days after inoculation. 37240010 4 29 theme highest 482:488 arg1 concentration 490:502 the highest concentration 478:502 the highest concentration 478:502 Both fungicides at the highest concentration decreased the nodule number and dry weight of the roots 20 days after inoculation. 37240010 8 30 theme further 1404:1410 arg1 research 1412:1419 further research 1404:1419 further research on the effects of pesticides on the legume-Rhizobium symbiosis in order to optimize their use 1404:1513 The data obtained indicate the need for further research on the effects of pesticides on the legume-Rhizobium symbiosis in order to optimize their use. 37240010 6 31 theme microfibrils 1083:1094 arg1 synthesis 1060:1068 synthesis 1060:1068 synthesis of cellulose microfibrils 1060:1094 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 1 32 theme agricultural 155:166 arg1 production 168:177 agricultural production 155:177 agricultural production 155:177 Triazole fungicides are widely used in agricultural production for plant protection, including pea (Pisum sativum L.). 37240010 0 33 theme Fungicides 19:28 arg1 Effect 0:5 Effect 0:5 Effect of Triazole Fungicides 0:28 Effect of Triazole Fungicides Titul Duo and Vintage on the Development of Pea (Pisum sativum L.) Symbiotic Nodules. 37240010 5 34 theme ultrastructural 643:657 arg1 changes 659:665 the following ultrastructural changes 629:665 the following ultrastructural changes in nodules 629:676 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 34 theme ultrastructural 643:657 arg1 thickening 742:751 thickening 742:751 thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes 742:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 35 from bacteroids 860:869 arg1 formation 792:800 the formation 788:800 the formation of outgrowths 788:814 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 35 from bacteroids 860:869 arg1 fusion 914:919 fusion 914:919 fusion of symbiosomes 914:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 35 from bacteroids 860:869 arg1 accumulation 817:828 accumulation 817:828 accumulation of poly-β-hydroxybutyrates in bacteroids 817:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 35 from bacteroids 860:869 arg1 expansion 872:880 expansion 872:880 expansion of the peribacteroid space 872:907 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 2 36 theme fungicides 246:255 arg1 use 239:241 The use 235:241 The use of fungicides 235:255 The use of fungicides can negatively affect the legume-Rhizobium symbiosis. 37240010 5 37 theme infection 760:768 arg1 walls 777:781 the infection thread walls 756:781 the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes 756:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 0 38 theme Triazole 10:17 arg1 Fungicides 19:28 Triazole Fungicides 10:28 Triazole Fungicides 10:28 Effect of Triazole Fungicides Titul Duo and Vintage on the Development of Pea (Pisum sativum L.) Symbiotic Nodules. 37240010 1 39 dep pea 211:213 arg1 sativum 222:228 Pisum sativum 216:228 Pisum sativum L. 216:231 Triazole fungicides are widely used in agricultural production for plant protection, including pea (Pisum sativum L.). 37240010 5 40 theme space 903:907 arg1 formation 792:800 the formation 788:800 the formation of outgrowths 788:814 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 40 theme space 903:907 arg1 fusion 914:919 fusion 914:919 fusion of symbiosomes 914:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 40 theme space 903:907 arg1 accumulation 817:828 accumulation 817:828 accumulation of poly-β-hydroxybutyrates in bacteroids 817:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 40 theme space 903:907 arg1 expansion 872:880 expansion 872:880 expansion of the peribacteroid space 872:907 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 4 41 theme roots 554:558 arg1 number 525:530 nodule number 518:530 nodule number 518:530 Both fungicides at the highest concentration decreased the nodule number and dry weight of the roots 20 days after inoculation. 37240010 4 41 theme roots 554:558 arg1 weight 540:545 dry weight 536:545 dry weight 536:545 Both fungicides at the highest concentration decreased the nodule number and dry weight of the roots 20 days after inoculation. 37240010 3 42 theme nodule 426:431 arg1 morphology 433:442 nodule morphology 426:442 nodule morphology 426:442 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 0 43 theme Nodules 107:113 arg1 Development 59:69 the Development 55:69 the Development of Pea (Pisum sativum L.) Symbiotic Nodules 55:113 Effect of Triazole Fungicides Titul Duo and Vintage on the Development of Pea (Pisum sativum L.) Symbiotic Nodules. 37240010 4 44 dep number 525:530 arg1 the 514:516 the 514:516 the 514:516 Both fungicides at the highest concentration decreased the nodule number and dry weight of the roots 20 days after inoculation. 37240010 7 45 theme cell 1318:1321 arg1 modification 1328:1339 cell wall modification 1318:1339 cell wall modification 1318:1339 The results obtained coincide well with the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions. 37240010 5 46 theme outgrowths 805:814 arg1 formation 792:800 the formation 788:800 the formation of outgrowths 788:814 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 46 theme outgrowths 805:814 arg1 fusion 914:919 fusion 914:919 fusion of symbiosomes 914:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 46 theme outgrowths 805:814 arg1 accumulation 817:828 accumulation 817:828 accumulation of poly-β-hydroxybutyrates in bacteroids 817:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 46 theme outgrowths 805:814 arg1 expansion 872:880 expansion 872:880 expansion of the peribacteroid space 872:907 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 1 47 theme plant 183:187 arg1 protection 189:198 plant protection 183:198 plant protection 183:198 Triazole fungicides are widely used in agricultural production for plant protection, including pea (Pisum sativum L.). 37240010 0 48 theme Symbiotic 97:105 arg1 Nodules 107:113 Pea (Pisum sativum L.) Symbiotic Nodules 74:113 Pea (Pisum sativum L.) Symbiotic Nodules 74:113 Effect of Triazole Fungicides Titul Duo and Vintage on the Development of Pea (Pisum sativum L.) Symbiotic Nodules. 37240010 0 48 theme Symbiotic 97:105 arg1 Pisum 79:83 Pisum 79:83 Pisum 79:83 Effect of Triazole Fungicides Titul Duo and Vintage on the Development of Pea (Pisum sativum L.) Symbiotic Nodules. 37240010 4 49 dep days 563:566 arg1 inoculation 574:584 inoculation 574:584 inoculation 574:584 Both fungicides at the highest concentration decreased the nodule number and dry weight of the roots 20 days after inoculation. 37240010 7 50 theme genes 1299:1303 arg1 levels 1289:1294 the expression levels 1274:1294 the expression levels of genes that control cell wall modification and defense reactions 1274:1361 The results obtained coincide well with the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions. 37240010 7 51 theme transcriptomic 1219:1232 arg1 analysis 1234:1241 transcriptomic analysis 1219:1241 transcriptomic analysis 1219:1241 The results obtained coincide well with the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions. 37240010 3 52 theme triazole 341:348 arg1 fungicides 350:359 triazole fungicides Vintage and Titul Duo 341:381 triazole fungicides Vintage and Titul Duo 341:381 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 3 52 theme triazole 341:348 arg1 Vintage 361:367 Vintage 361:367 Vintage 361:367 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 3 52 theme triazole 341:348 arg1 Duo 379:381 Duo 379:381 Duo 379:381 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 5 53 from modifications 679:691 arg1 walls 705:709 the cell walls 696:709 the cell walls 696:709 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 6 54 theme cell 1155:1158 arg1 walls 1160:1164 cell walls 1155:1164 cell walls 1155:1164 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 8 55 theme legume-Rhizobium 1457:1472 arg1 symbiosis 1474:1482 the legume-Rhizobium symbiosis 1453:1482 the legume-Rhizobium symbiosis in order to optimize their use 1453:1513 The data obtained indicate the need for further research on the effects of pesticides on the legume-Rhizobium symbiosis in order to optimize their use. 37240010 6 56 theme synthesis 1060:1068 arg1 activity 1048:1055 the activity 1044:1055 the activity of synthesis of cellulose microfibrils 1044:1094 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 3 57 theme fungicides 350:359 arg1 effects 330:336 the effects 326:336 the effects 326:336 In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. 37240010 6 58 dep Fungicides 937:946 arg1 Fungicides 937:946 Fungicides Vintage and Titul Duo 937:968 Fungicides Vintage and Titul Duo 937:968 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 6 58 dep Fungicides 937:946 arg1 Vintage 948:954 Vintage 948:954 Vintage 948:954 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 6 58 dep Fungicides 937:946 arg1 Duo 966:968 Duo 966:968 Duo 966:968 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 5 59 with walls 777:781 arg1 formation 792:800 the formation 788:800 the formation of outgrowths 788:814 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 59 with walls 777:781 arg1 fusion 914:919 fusion 914:919 fusion of symbiosomes 914:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 59 with walls 777:781 arg1 accumulation 817:828 accumulation 817:828 accumulation of poly-β-hydroxybutyrates in bacteroids 817:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 59 with walls 777:781 arg1 expansion 872:880 expansion 872:880 expansion of the peribacteroid space 872:907 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 6 60 theme cellulose 1073:1081 arg1 microfibrils 1083:1094 cellulose microfibrils 1073:1094 cellulose microfibrils 1073:1094 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 2 61 theme legume-Rhizobium 283:298 arg1 symbiosis 300:308 the legume-Rhizobium symbiosis 279:308 the legume-Rhizobium symbiosis 279:308 The use of fungicides can negatively affect the legume-Rhizobium symbiosis. 37240010 6 62 theme polysaccharides 1136:1150 arg1 number 1119:1124 the number 1115:1124 the number of matrix polysaccharides of cell walls 1115:1164 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 5 63 theme symbiosomes 924:934 arg1 formation 792:800 the formation 788:800 the formation of outgrowths 788:814 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 63 theme symbiosomes 924:934 arg1 fusion 914:919 fusion 914:919 fusion of symbiosomes 914:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 63 theme symbiosomes 924:934 arg1 accumulation 817:828 accumulation 817:828 accumulation of poly-β-hydroxybutyrates in bacteroids 817:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 63 theme symbiosomes 924:934 arg1 expansion 872:880 expansion 872:880 expansion of the peribacteroid space 872:907 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 6 64 theme walls 1160:1164 arg1 polysaccharides 1136:1150 matrix polysaccharides 1129:1150 matrix polysaccharides of cell walls 1129:1164 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 5 65 theme peribacteroid 889:901 arg1 space 903:907 the peribacteroid space 885:907 the peribacteroid space 885:907 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 7 66 theme wall 1323:1326 arg1 modification 1328:1339 cell wall modification 1318:1339 cell wall modification 1318:1339 The results obtained coincide well with the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions. 37240010 5 67 theme following 633:641 arg1 changes 659:665 the following ultrastructural changes 629:665 the following ultrastructural changes in nodules 629:676 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 67 theme following 633:641 arg1 thickening 742:751 thickening 742:751 thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes 742:934 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 6 68 theme cell 1007:1010 arg1 walls 1012:1016 cell walls 1007:1016 cell walls 1007:1016 Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. 37240010 4 69 theme dry 536:538 arg1 weight 540:545 dry weight 536:545 dry weight 536:545 Both fungicides at the highest concentration decreased the nodule number and dry weight of the roots 20 days after inoculation. 37240010 5 70 theme cell 700:703 arg1 walls 705:709 the cell walls 696:709 the cell walls 696:709 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 1 71 dep sativum 222:228 arg1 L 230:230 L 230:230 Pisum sativum L. 216:231 Triazole fungicides are widely used in agricultural production for plant protection, including pea (Pisum sativum L.). 37240010 1 72 used used 147:150 arg2 fungicides 125:134 Triazole fungicides 116:134 Triazole fungicides 116:134 Triazole fungicides are widely used in agricultural production for plant protection, including pea (Pisum sativum L.). 37240010 7 73 theme analysis 1234:1241 arg1 data 1211:1214 the data 1207:1214 the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions 1207:1361 The results obtained coincide well with the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions. 37240010 5 74 dep modifications 679:691 arg1 thinning 731:738 thinning 731:738 thinning 731:738 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 74 dep modifications 679:691 arg1 clearing 718:725 their clearing 712:725 their clearing 712:725 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 5 74 dep modifications 679:691 arg1 modifications 679:691 modifications 679:691 modifications in the cell walls (their clearing and thinning) 679:739 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 37240010 7 75 theme expression 1278:1287 arg1 levels 1289:1294 the expression levels 1274:1294 the expression levels of genes that control cell wall modification and defense reactions 1274:1361 The results obtained coincide well with the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions. 37240010 1 76 theme Triazole 116:123 arg1 fungicides 125:134 Triazole fungicides 116:134 Triazole fungicides 116:134 Triazole fungicides are widely used in agricultural production for plant protection, including pea (Pisum sativum L.). 37240010 5 77 from fusion 914:919 arg1 bacteroids 860:869 bacteroids 860:869 bacteroids 860:869 Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. 35359742 7 0 dep morphology 769:778 arg1 The 765:767 The 765:767 The 765:767 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 12 1 theme sulfite 1803:1809 arg1 reductase 1811:1819 sulfite reductase 1803:1819 sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy 1803:1897 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 7 2 with scattering 870:879 arg1 spectrometry 958:969 energy-dispersive X-ray (EDX) spectrometry 928:969 energy-dispersive X-ray (EDX) spectrometry 928:969 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 7 3 dep infrared 994:1001 arg1 FTIR 1004:1007 FTIR 1004:1007 FTIR 1004:1007 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 10 4 theme SeNPs 1391:1395 arg1 mechanism 1361:1369 the selenite reduction mechanism 1338:1369 the selenite reduction mechanism 1338:1369 Comparative transcriptome analysis was performed to elucidate the selenite reduction mechanism and biosynthesis of SeNPs. 35359742 10 4 theme SeNPs 1391:1395 arg1 biosynthesis 1375:1386 biosynthesis 1375:1386 biosynthesis of SeNPs 1375:1395 Comparative transcriptome analysis was performed to elucidate the selenite reduction mechanism and biosynthesis of SeNPs. 35359742 2 5 from detoxification 224:237 arg1 cases 243:247 cases 243:247 cases of dissimilatory reduction 243:274 Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). 35359742 7 6 theme purified 816:823 arg1 SeNPs 825:829 the isolated and purified SeNPs 799:829 SeNPs 825:829 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 8 7 theme SeNPs 1137:1141 arg1 surface 1113:1119 the surface 1109:1119 the surface of the isolated SeNPs 1109:1141 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 6 8 theme 5.0 mM 572:577 arg1 selenite 579:586 5.0 mM selenite 572:586 5.0 mM selenite 572:586 Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. 35359742 13 9 theme selenite 1966:1973 arg1 stress 1975:1980 selenite stress 1966:1980 selenite stress 1966:1980 This work suggests numerous genes are involved in the response to selenite stress, providing new insights into the molecular mechanisms of selenite bioreduction with the formation of SeNPs. 35359742 7 10 theme isolated 803:810 arg1 SeNPs 825:829 the isolated and purified SeNPs 799:829 SeNPs 825:829 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 13 11 theme numerous 1919:1926 arg1 genes 1928:1932 numerous genes 1919:1932 numerous genes 1919:1932 This work suggests numerous genes are involved in the response to selenite stress, providing new insights into the molecular mechanisms of selenite bioreduction with the formation of SeNPs. 35359742 1 12 dep YS02 34:37 arg1 Insights 44:51 New Insights 40:51 YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles. 34:158 YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles. 35359742 9 13 theme excellent 1174:1182 arg1 activity 1198:1205 excellent antimicrobial activity 1174:1205 excellent antimicrobial activity against several Gram-positive and Gram-negative pathogenic bacteria 1174:1273 Furthermore, the SeNPs showed excellent antimicrobial activity against several Gram-positive and Gram-negative pathogenic bacteria. 35359742 9 14 theme several 1215:1221 arg1 bacteria 1266:1273 several Gram-positive and Gram-negative pathogenic bacteria 1215:1273 several Gram-positive and Gram-negative pathogenic bacteria 1215:1273 Furthermore, the SeNPs showed excellent antimicrobial activity against several Gram-positive and Gram-negative pathogenic bacteria. 35359742 7 15 theme infrared 994:1001 arg1 spectroscopy 1010:1021 infrared (FTIR) spectroscopy 994:1021 infrared (FTIR) spectroscopy 994:1021 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 7 16 theme EDX 953:955 arg1 spectrometry 958:969 energy-dispersive X-ray (EDX) spectrometry 928:969 energy-dispersive X-ray (EDX) spectrometry 928:969 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 1 17 theme Biogenic 132:139 arg1 Nanoparticles 145:157 the Biogenic Se0 Nanoparticles 128:157 the Biogenic Se0 Nanoparticles 128:157 YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles. 35359742 12 18 theme pyruvate 1717:1724 arg1 dehydrogenase 1726:1738 pyruvate dehydrogenase 1717:1738 pyruvate dehydrogenase 1717:1738 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 9 19 theme pathogenic 1255:1264 arg1 bacteria 1266:1273 several Gram-positive and Gram-negative pathogenic bacteria 1215:1273 several Gram-positive and Gram-negative pathogenic bacteria 1215:1273 Furthermore, the SeNPs showed excellent antimicrobial activity against several Gram-positive and Gram-negative pathogenic bacteria. 35359742 2 20 theme dissimilatory 252:264 arg1 reduction 266:274 dissimilatory reduction 252:274 dissimilatory reduction 252:274 Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). 35359742 7 21 theme X-ray 946:950 arg1 spectrometry 958:969 energy-dispersive X-ray (EDX) spectrometry 928:969 energy-dispersive X-ray (EDX) spectrometry 928:969 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 8 22 from presence 1056:1063 arg1 surface 1113:1119 the surface 1109:1119 the surface of the isolated SeNPs 1109:1141 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 11 23 theme 197 1418:1420 arg1 genes 1422:1426 197 genes 1418:1426 197 genes 1418:1426 It is revealed that 197 genes were significantly upregulated, and 276 genes were significantly downregulated under selenite treatment. 35359742 4 24 theme selenite-resistant 465:482 arg1 bacterium 484:492 a selenite-resistant bacterium 463:492 a selenite-resistant bacterium 463:492 In this study, a selenite-resistant bacterium was isolated and identified as Proteus sp. 35359742 4 24 theme selenite-resistant 465:482 arg1 sp 533:534 Proteus sp 525:534 Proteus sp 525:534 In this study, a selenite-resistant bacterium was isolated and identified as Proteus sp. 35359742 12 25 theme ontology 1538:1545 arg1 analyses 1598:1605 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses 1533:1605 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses 1533:1605 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 13 26 theme new 1993:1995 arg1 insights 1997:2004 new insights 1993:2004 new insights into the molecular mechanisms of selenite bioreduction 1993:2059 This work suggests numerous genes are involved in the response to selenite stress, providing new insights into the molecular mechanisms of selenite bioreduction with the formation of SeNPs. 35359742 7 27 with Fourier 976:982 arg1 spectrometry 958:969 energy-dispersive X-ray (EDX) spectrometry 928:969 energy-dispersive X-ray (EDX) spectrometry 928:969 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 3 28 theme selenite 412:419 arg1 reduction 421:429 selenite reduction 412:429 selenite reduction 412:429 However, the current knowledge of the molecular mechanism of selenite reduction remains limited. 35359742 12 29 theme pentose 1680:1686 arg1 PPP 1707:1709 PPP 1707:1709 PPP 1707:1709 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 12 29 theme pentose 1680:1686 arg1 pathway 1698:1704 pentose phosphate pathway 1680:1704 pentose phosphate pathway (PPP) 1680:1710 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 7 30 dep Fourier 976:982 arg1 transform 984:992 transform 984:992 transform infrared (FTIR) spectroscopy 984:1021 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 3 31 theme mechanism 399:407 arg1 knowledge 372:380 the current knowledge 360:380 the current knowledge of the molecular mechanism of selenite reduction 360:429 However, the current knowledge of the molecular mechanism of selenite reduction remains limited. 35359742 7 32 theme scanning 888:895 arg1 microscopy 906:915 scanning electron microscopy 888:915 scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry 888:969 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 7 32 theme scanning 888:895 arg1 SEM 918:920 SEM 918:920 SEM 918:920 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 12 33 theme ABC 1643:1645 arg1 transporters 1647:1658 ABC transporters 1643:1658 ABC transporters 1643:1658 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 1 34 theme Antibacterial 97:109 arg1 Effectiveness 111:123 Antibacterial Effectiveness 97:123 Antibacterial Effectiveness 97:123 YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles. 35359742 10 35 theme transcriptome 1288:1300 arg1 analysis 1302:1309 Comparative transcriptome analysis 1276:1309 Comparative transcriptome analysis 1276:1309 Comparative transcriptome analysis was performed to elucidate the selenite reduction mechanism and biosynthesis of SeNPs. 35359742 12 36 theme Gene 1533:1536 arg1 ontology 1538:1545 Gene ontology 1533:1545 Gene ontology 1533:1545 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 13 37 theme selenite 2039:2046 arg1 bioreduction 2048:2059 selenite bioreduction 2039:2059 selenite bioreduction 2039:2059 This work suggests numerous genes are involved in the response to selenite stress, providing new insights into the molecular mechanisms of selenite bioreduction with the formation of SeNPs. 35359742 11 38 theme selenite 1513:1520 arg1 treatment 1522:1530 selenite treatment 1513:1530 selenite treatment 1513:1530 It is revealed that 197 genes were significantly upregulated, and 276 genes were significantly downregulated under selenite treatment. 35359742 12 39 theme pyruvate 1834:1841 arg1 dehydrogenase 1843:1855 pyruvate dehydrogenase 1834:1855 pyruvate dehydrogenase 1834:1855 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 2 40 theme effective 214:222 arg1 Biotransformation 160:176 Biotransformation 160:176 Biotransformation of selenite by microorganisms 160:206 Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). 35359742 2 40 theme effective 214:222 arg1 detoxification 224:237 an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process 211:314 detoxification 224:237 Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). 35359742 12 41 theme reducing 1867:1874 arg1 equivalents 1876:1886 reducing equivalents 1867:1886 reducing equivalents 1867:1886 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 10 42 theme selenite 1342:1349 arg1 mechanism 1361:1369 the selenite reduction mechanism 1338:1369 the selenite reduction mechanism 1338:1369 Comparative transcriptome analysis was performed to elucidate the selenite reduction mechanism and biosynthesis of SeNPs. 35359742 8 43 attach presence 1056:1063 arg2 polysaccharides 1078:1092 polysaccharides 1078:1092 polysaccharides 1078:1092 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 8 43 attach presence 1056:1063 arg1 surface 1113:1119 the surface 1109:1119 the surface of the isolated SeNPs 1109:1141 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 8 43 attach presence 1056:1063 arg2 proteins 1068:1075 proteins 1068:1075 proteins 1068:1075 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 8 43 attach presence 1056:1063 arg2 lipids 1099:1104 lipids 1099:1104 lipids 1099:1104 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 10 44 theme reduction 1351:1359 arg1 mechanism 1361:1369 the selenite reduction mechanism 1338:1369 the selenite reduction mechanism 1338:1369 Comparative transcriptome analysis was performed to elucidate the selenite reduction mechanism and biosynthesis of SeNPs. 35359742 8 45 theme lipids 1099:1104 arg1 presence 1056:1063 the presence 1052:1063 the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs 1052:1141 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 7 46 theme dynamic 856:862 arg1 DLS 882:884 DLS 882:884 DLS 882:884 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 7 46 theme dynamic 856:862 arg1 scattering 870:879 dynamic light scattering 856:879 dynamic light scattering (DLS) 856:885 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 6 47 theme selenite 579:586 arg1 % 567:567 93.2% 563:567 93.2% of 5.0 mM selenite 563:586 Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. 35359742 6 47 theme selenite 579:586 arg1 selenite 579:586 5.0 mM selenite 572:586 5.0 mM selenite 572:586 Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. 35359742 6 48 theme 140 ± 43 nm 752:762 arg1 dimension 739:747 an average dimension 728:747 an average dimension of 140 ± 43 nm 728:762 Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. 35359742 7 49 theme SeNPs 825:829 arg1 morphology 769:778 morphology 769:778 morphology 769:778 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 7 49 theme SeNPs 825:829 arg1 composition 784:794 composition 784:794 composition 784:794 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 8 50 theme isolated 1128:1135 arg1 SeNPs 1137:1141 the isolated SeNPs 1124:1141 the isolated SeNPs 1124:1141 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 2 51 theme assimilation 295:306 arg1 process 308:314 an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process 211:314 process 308:314 Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). 35359742 12 52 with reductase 1811:1819 arg1 PPP 1826:1828 PPP 1826:1828 PPP 1826:1828 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 12 52 with reductase 1811:1819 arg1 dehydrogenase 1843:1855 pyruvate dehydrogenase 1834:1855 pyruvate dehydrogenase 1834:1855 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 7 53 with microscopy 906:915 arg1 spectrometry 958:969 energy-dispersive X-ray (EDX) spectrometry 928:969 energy-dispersive X-ray (EDX) spectrometry 928:969 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 9 54 theme antimicrobial 1184:1196 arg1 activity 1198:1205 excellent antimicrobial activity 1174:1205 excellent antimicrobial activity against several Gram-positive and Gram-negative pathogenic bacteria 1174:1273 Furthermore, the SeNPs showed excellent antimicrobial activity against several Gram-positive and Gram-negative pathogenic bacteria. 35359742 2 55 dep cases 243:247 arg1 e.g. 277:280 e.g. 277:280 e.g. 277:280 Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). 35359742 9 56 theme Gram-positive 1223:1235 arg1 bacteria 1266:1273 several Gram-positive and Gram-negative pathogenic bacteria 1215:1273 several Gram-positive and Gram-negative pathogenic bacteria 1215:1273 Furthermore, the SeNPs showed excellent antimicrobial activity against several Gram-positive and Gram-negative pathogenic bacteria. 35359742 12 57 theme Genes 1573:1577 arg1 ontology 1538:1545 Gene ontology 1533:1545 Gene ontology 1533:1545 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 9 58 theme Gram-negative 1241:1253 arg1 bacteria 1266:1273 several Gram-positive and Gram-negative pathogenic bacteria 1215:1273 several Gram-positive and Gram-negative pathogenic bacteria 1215:1273 Furthermore, the SeNPs showed excellent antimicrobial activity against several Gram-positive and Gram-negative pathogenic bacteria. 35359742 2 59 theme reduction 266:274 arg1 cases 243:247 cases 243:247 cases of dissimilatory reduction 243:274 Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). 35359742 1 60 theme Se0 141:143 arg1 Nanoparticles 145:157 the Biogenic Se0 Nanoparticles 128:157 the Biogenic Se0 Nanoparticles 128:157 YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles. 35359742 12 61 theme Genomes 1583:1589 arg1 ontology 1538:1545 Gene ontology 1533:1545 Gene ontology 1533:1545 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 12 62 theme phosphate 1688:1696 arg1 PPP 1707:1709 PPP 1707:1709 PPP 1707:1709 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 12 62 theme phosphate 1688:1696 arg1 pathway 1698:1704 pentose phosphate pathway 1680:1704 pentose phosphate pathway (PPP) 1680:1710 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 6 63 theme selenium 591:598 arg1 nanoparticles 600:612 selenium nanoparticles 591:612 selenium nanoparticles (SeNPs) within 24 h 591:632 Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. 35359742 6 63 theme selenium 591:598 arg1 SeNPs 615:619 SeNPs 615:619 SeNPs 615:619 Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. 35359742 7 64 theme energy-dispersive 928:944 arg1 spectrometry 958:969 energy-dispersive X-ray (EDX) spectrometry 928:969 energy-dispersive X-ray (EDX) spectrometry 928:969 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 1 65 theme New 40:42 arg1 Insights 44:51 New Insights 40:51 YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles. 34:158 YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles. 35359742 2 66 from process 308:314 arg1 cases 243:247 cases 243:247 cases of dissimilatory reduction 243:274 Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). 35359742 12 67 theme Encyclopedia 1557:1568 arg1 analyses 1598:1605 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses 1533:1605 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses 1533:1605 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 10 68 theme Comparative 1276:1286 arg1 analysis 1302:1309 Comparative transcriptome analysis 1276:1309 Comparative transcriptome analysis 1276:1309 Comparative transcriptome analysis was performed to elucidate the selenite reduction mechanism and biosynthesis of SeNPs. 35359742 12 69 theme sulfur 1661:1666 arg1 metabolism 1668:1677 sulfur metabolism 1661:1677 sulfur metabolism 1661:1677 Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that genes associated with ABC transporters, sulfur metabolism, pentose phosphate pathway (PPP), and pyruvate dehydrogenase were significantly enhanced, indicating selenite is reduced by sulfite reductase with PPP and pyruvate dehydrogenase supplying reducing equivalents and energy. 35359742 3 70 theme reduction 421:429 arg1 mechanism 399:407 the molecular mechanism 385:407 the molecular mechanism of selenite reduction 385:429 However, the current knowledge of the molecular mechanism of selenite reduction remains limited. 35359742 13 71 theme SeNPs 2083:2087 arg1 formation 2070:2078 the formation 2066:2078 the formation of SeNPs 2066:2087 This work suggests numerous genes are involved in the response to selenite stress, providing new insights into the molecular mechanisms of selenite bioreduction with the formation of SeNPs. 35359742 8 72 theme FTIR 1024:1027 arg1 spectroscopy 1029:1040 FTIR spectroscopy 1024:1040 FTIR spectroscopy 1024:1040 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 1 73 theme Comparative 65:75 arg1 Transcriptomics 77:91 Comparative Transcriptomics 65:91 Comparative Transcriptomics 65:91 YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles. 35359742 3 74 theme current 364:370 arg1 knowledge 372:380 the current knowledge 360:380 the current knowledge of the molecular mechanism of selenite reduction 360:429 However, the current knowledge of the molecular mechanism of selenite reduction remains limited. 35359742 6 75 theme produced 643:650 arg1 spherical 663:671 spherical 663:671 spherical 663:671 Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. 35359742 6 75 theme produced 643:650 arg1 SeNPs 652:656 the produced SeNPs 639:656 the produced SeNPs 639:656 Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. 35359742 0 76 theme Proteus 22:28 arg1 sp 30:31 Proteus sp 22:31 Proteus sp 22:31 Selenite Reduction by Proteus sp. 35359742 7 77 theme electron 897:904 arg1 microscopy 906:915 scanning electron microscopy 888:915 scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry 888:969 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 7 77 theme electron 897:904 arg1 SEM 918:920 SEM 918:920 SEM 918:920 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 3 78 theme molecular 389:397 arg1 mechanism 399:407 the molecular mechanism 385:407 the molecular mechanism of selenite reduction 385:429 However, the current knowledge of the molecular mechanism of selenite reduction remains limited. 35359742 6 79 with spherical 663:671 arg1 dimension 739:747 an average dimension 728:747 an average dimension of 140 ± 43 nm 728:762 Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. 35359742 2 80 theme selenite 181:188 arg1 detoxification 224:237 an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process 211:314 detoxification 224:237 Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). 35359742 2 80 theme selenite 181:188 arg1 Biotransformation 160:176 Biotransformation 160:176 Biotransformation of selenite by microorganisms 160:206 Biotransformation of selenite by microorganisms is an effective detoxification (in cases of dissimilatory reduction, e.g., to Se0) and assimilation process (when Se is assimilated by cells). 35359742 6 81 theme average 731:737 arg1 dimension 739:747 an average dimension 728:747 an average dimension of 140 ± 43 nm 728:762 Strain YS02 reduced 93.2% of 5.0 mM selenite to selenium nanoparticles (SeNPs) within 24 h, and the produced SeNPs were spherical and localized intracellularly or extracellularly, with an average dimension of 140 ± 43 nm. 35359742 8 82 theme proteins 1068:1075 arg1 presence 1056:1063 the presence 1052:1063 the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs 1052:1141 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 4 83 theme Proteus 525:531 arg1 bacterium 484:492 a selenite-resistant bacterium 463:492 a selenite-resistant bacterium 463:492 In this study, a selenite-resistant bacterium was isolated and identified as Proteus sp. 35359742 4 83 theme Proteus 525:531 arg1 sp 533:534 Proteus sp 525:534 Proteus sp 525:534 In this study, a selenite-resistant bacterium was isolated and identified as Proteus sp. 35359742 1 84 theme Nanoparticles 145:157 arg1 Transcriptomics 77:91 Comparative Transcriptomics 65:91 Comparative Transcriptomics 65:91 YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles. 35359742 1 84 theme Nanoparticles 145:157 arg1 Effectiveness 111:123 Antibacterial Effectiveness 97:123 Antibacterial Effectiveness 97:123 YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles. 35359742 13 85 theme bioreduction 2048:2059 arg1 mechanisms 2025:2034 the molecular mechanisms 2011:2034 the molecular mechanisms of selenite bioreduction 2011:2059 This work suggests numerous genes are involved in the response to selenite stress, providing new insights into the molecular mechanisms of selenite bioreduction with the formation of SeNPs. 35359742 8 86 theme polysaccharides 1078:1092 arg1 presence 1056:1063 the presence 1052:1063 the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs 1052:1141 FTIR spectroscopy indicated the presence of proteins, polysaccharides, and lipids on the surface of the isolated SeNPs. 35359742 13 87 theme molecular 2015:2023 arg1 mechanisms 2025:2034 the molecular mechanisms 2011:2034 the molecular mechanisms of selenite bioreduction 2011:2059 This work suggests numerous genes are involved in the response to selenite stress, providing new insights into the molecular mechanisms of selenite bioreduction with the formation of SeNPs. 35359742 7 88 theme light 864:868 arg1 DLS 882:884 DLS 882:884 DLS 882:884 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 35359742 7 88 theme light 864:868 arg1 scattering 870:879 dynamic light scattering 856:879 dynamic light scattering (DLS) 856:885 The morphology and composition of the isolated and purified SeNPs were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) spectrometry, and Fourier transform infrared (FTIR) spectroscopy. 36336076 7 0 theme reticulum 1099:1107 arg1 localization 1109:1120 increased endoplasmic reticulum localization 1077:1120 increased endoplasmic reticulum localization 1077:1120 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 2 1 theme catalytic 351:359 arg1 domain 361:366 its large C-terminal catalytic domain 330:366 its large C-terminal catalytic domain 330:366 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 5 2 theme FUT8Δstem 711:719 arg1 mutants 721:727 FUT8Δstem mutants 711:727 FUT8Δstem mutants 711:727 We expressed FUT8Δstem mutants, in which the stem region was replaced with glycine/serine linkers, in FUT8-KO HEK293 cells. 36336076 9 3 theme mammalian 1606:1614 arg1 cells 1616:1620 mammalian cells 1606:1620 mammalian cells 1606:1620 Our findings demonstrated that the FUT8 stem region is essential for multimer formation but not for catalytic activity, providing insights into how the FUT8 protein matures and functions in mammalian cells. 36336076 1 4 from fucose 164:169 arg1 N-glycans 174:182 N-glycans 174:182 N-glycans 174:182 Alpha-1,6-fucosyltransferase (FUT8) synthesizes core fucose in N-glycans, which plays critical roles in various physiological processes. 36336076 2 5 theme C-terminal 340:349 arg1 domain 361:366 its large C-terminal catalytic domain 330:366 its large C-terminal catalytic domain 330:366 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 9 6 theme FUT8 1451:1454 arg1 region 1461:1466 the FUT8 stem region 1447:1466 the FUT8 stem region 1447:1466 Our findings demonstrated that the FUT8 stem region is essential for multimer formation but not for catalytic activity, providing insights into how the FUT8 protein matures and functions in mammalian cells. 36336076 9 6 theme FUT8 1451:1454 arg1 essential 1471:1479 essential 1471:1479 essential 1471:1479 Our findings demonstrated that the FUT8 stem region is essential for multimer formation but not for catalytic activity, providing insights into how the FUT8 protein matures and functions in mammalian cells. 36336076 0 7 theme catalytic 91:99 arg1 activity 101:108 catalytic activity 91:108 multimer formation but not catalytic activity 64:108 The stem region of α1,6-fucosyltransferase FUT8 is required for multimer formation but not catalytic activity. 36336076 6 8 theme FUT8 883:886 arg1 WT 888:889 FUT8 WT 883:889 FUT8 WT 883:889 Our immunoprecipitation and native-PAGE analysis showed that FUT8 WT formed a multimer but FUT8Δstem impaired multimer formation in the cells, although the mutants retained specific activity. 36336076 7 9 theme increased 1077:1085 arg1 localization 1109:1120 increased endoplasmic reticulum localization 1077:1120 increased endoplasmic reticulum localization 1077:1120 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 8 10 theme stem 1368:1371 arg1 region 1373:1378 the FUT8 stem region 1359:1378 the FUT8 stem region 1359:1378 Furthermore, immunoprecipitation analysis of another mutant lacking a part of the stem region revealed that the first helix in the FUT8 stem region is critical for multimer formation. 36336076 3 11 theme localization 532:543 arg1 regulation 512:521 the regulation 508:521 the regulation of Golgi localization 508:543 Although the stem regions of several glycosyltransferases are involved in the regulation of Golgi localization, the functions of the FUT8 stem region have not been clarified as yet. 36336076 7 12 theme endoplasmic 1087:1097 arg1 reticulum 1099:1107 endoplasmic reticulum 1087:1107 increased endoplasmic reticulum localization 1077:1120 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 9 13 theme multimer 1485:1492 arg1 formation 1494:1502 multimer formation 1485:1502 multimer formation 1485:1502 Our findings demonstrated that the FUT8 stem region is essential for multimer formation but not for catalytic activity, providing insights into how the FUT8 protein matures and functions in mammalian cells. 36336076 4 14 theme enzyme 674:679 arg1 oligomerization 681:695 enzyme oligomerization 674:695 enzyme oligomerization 674:695 Here, we found that the FUT8 stem region is essential for enzyme oligomerization. 36336076 3 15 theme glycosyltransferases 471:490 arg1 regions 452:458 the stem regions 443:458 the stem regions of several glycosyltransferases 443:490 Although the stem regions of several glycosyltransferases are involved in the regulation of Golgi localization, the functions of the FUT8 stem region have not been clarified as yet. 36336076 2 16 theme FUT8 385:388 arg1 region 395:400 the FUT8 stem region 381:400 the FUT8 stem region 381:400 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 2 17 dep as 254:255 arg1 with 257:260 with 257:260 with 257:260 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 7 18 dep lower 1050:1054 arg1 levels 1069:1074 steady-state levels 1056:1074 steady-state levels 1056:1074 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 2 19 theme other 267:271 arg1 FUT8 248:251 FUT8 248:251 FUT8 248:251 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 2 19 theme other 267:271 arg1 glycosyltransferases 273:292 many other glycosyltransferases 262:292 many other glycosyltransferases 262:292 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 2 19 theme other 267:271 arg1 protein 317:323 a type-II membrane protein 298:323 a type-II membrane protein 298:323 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 9 20 theme FUT8 1568:1571 arg1 protein 1573:1579 the FUT8 protein 1564:1579 the FUT8 protein 1564:1579 Our findings demonstrated that the FUT8 stem region is essential for multimer formation but not for catalytic activity, providing insights into how the FUT8 protein matures and functions in mammalian cells. 36336076 0 21 theme stem 4:7 arg1 region 9:14 The stem region 0:14 The stem region of α1,6-fucosyltransferase FUT8 0:46 The stem region of α1,6-fucosyltransferase FUT8 is required for multimer formation but not catalytic activity. 36336076 6 22 theme native-PAGE 850:860 arg1 analysis 862:869 Our immunoprecipitation and native-PAGE analysis 822:869 analysis 862:869 Our immunoprecipitation and native-PAGE analysis showed that FUT8 WT formed a multimer but FUT8Δstem impaired multimer formation in the cells, although the mutants retained specific activity. 36336076 7 23 theme stem 1189:1192 arg1 region 1194:1199 the stem region 1185:1199 the stem region 1185:1199 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 7 24 theme FUT8 1152:1155 arg1 WT 1157:1158 FUT8 WT 1152:1158 FUT8 WT 1152:1158 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 7 25 theme shorter 1129:1135 arg1 half-life 1137:1145 a shorter half-life 1127:1145 a shorter half-life 1127:1145 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 7 26 theme steady-state 1056:1067 arg1 levels 1069:1074 steady-state levels 1056:1074 steady-state levels 1056:1074 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 2 27 theme membrane 308:315 arg1 FUT8 248:251 FUT8 248:251 FUT8 248:251 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 2 27 theme membrane 308:315 arg1 glycosyltransferases 273:292 many other glycosyltransferases 262:292 many other glycosyltransferases 262:292 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 2 27 theme membrane 308:315 arg1 protein 317:323 a type-II membrane protein 298:323 a type-II membrane protein 298:323 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 5 28 theme glycine/serine 773:786 arg1 linkers 788:794 glycine/serine linkers 773:794 glycine/serine linkers 773:794 We expressed FUT8Δstem mutants, in which the stem region was replaced with glycine/serine linkers, in FUT8-KO HEK293 cells. 36336076 8 29 theme FUT8 1363:1366 arg1 region 1373:1378 the FUT8 stem region 1359:1378 the FUT8 stem region 1359:1378 Furthermore, immunoprecipitation analysis of another mutant lacking a part of the stem region revealed that the first helix in the FUT8 stem region is critical for multimer formation. 36336076 2 30 theme type-II 300:306 arg1 FUT8 248:251 FUT8 248:251 FUT8 248:251 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 2 30 theme type-II 300:306 arg1 glycosyltransferases 273:292 many other glycosyltransferases 262:292 many other glycosyltransferases 262:292 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 2 30 theme type-II 300:306 arg1 protein 317:323 a type-II membrane protein 298:323 a type-II membrane protein 298:323 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 1 31 theme critical 197:204 arg1 roles 206:210 critical roles 197:210 critical roles 197:210 Alpha-1,6-fucosyltransferase (FUT8) synthesizes core fucose in N-glycans, which plays critical roles in various physiological processes. 36336076 8 32 theme first 1344:1348 arg1 critical 1383:1390 critical 1383:1390 critical 1383:1390 Furthermore, immunoprecipitation analysis of another mutant lacking a part of the stem region revealed that the first helix in the FUT8 stem region is critical for multimer formation. 36336076 8 32 theme first 1344:1348 arg1 helix 1350:1354 the first helix 1340:1354 the first helix in the FUT8 stem region 1340:1378 Furthermore, immunoprecipitation analysis of another mutant lacking a part of the stem region revealed that the first helix in the FUT8 stem region is critical for multimer formation. 36336076 7 33 contain had 1046:1048 arg2 localization 1109:1120 increased endoplasmic reticulum localization 1077:1120 increased endoplasmic reticulum localization 1077:1120 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 7 33 contain had 1046:1048 arg2 lower 1050:1054 lower 1050:1054 lower 1050:1054 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 7 33 contain had 1046:1048 arg1 protein 1038:1044 the mutant protein 1027:1044 the mutant protein 1027:1044 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 7 33 contain had 1046:1048 arg2 half-life 1137:1145 a shorter half-life 1127:1145 a shorter half-life 1127:1145 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 7 34 theme FUT8 1218:1221 arg1 protein 1223:1229 the FUT8 protein 1214:1229 the FUT8 protein 1214:1229 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 0 35 theme FUT8 43:46 arg1 region 9:14 The stem region 0:14 The stem region of α1,6-fucosyltransferase FUT8 0:46 The stem region of α1,6-fucosyltransferase FUT8 is required for multimer formation but not catalytic activity. 36336076 6 36 theme multimer 932:939 arg1 formation 941:949 multimer formation 932:949 multimer formation 932:949 Our immunoprecipitation and native-PAGE analysis showed that FUT8 WT formed a multimer but FUT8Δstem impaired multimer formation in the cells, although the mutants retained specific activity. 36336076 8 37 theme multimer 1396:1403 arg1 formation 1405:1413 multimer formation 1396:1413 multimer formation 1396:1413 Furthermore, immunoprecipitation analysis of another mutant lacking a part of the stem region revealed that the first helix in the FUT8 stem region is critical for multimer formation. 36336076 3 38 theme region 577:582 arg1 functions 550:558 the functions 546:558 the functions of the FUT8 stem region 546:582 Although the stem regions of several glycosyltransferases are involved in the regulation of Golgi localization, the functions of the FUT8 stem region have not been clarified as yet. 36336076 5 39 theme FUT8-KO 800:806 arg1 HEK293 cells 808:819 FUT8-KO HEK293 cells 800:819 FUT8-KO HEK293 cells 800:819 We expressed FUT8Δstem mutants, in which the stem region was replaced with glycine/serine linkers, in FUT8-KO HEK293 cells. 36336076 0 40 theme α1,6-fucosyltransferase 19:41 arg1 FUT8 43:46 α1,6-fucosyltransferase FUT8 19:46 α1,6-fucosyltransferase FUT8 19:46 The stem region of α1,6-fucosyltransferase FUT8 is required for multimer formation but not catalytic activity. 36336076 5 41 theme stem 743:746 arg1 region 748:753 the stem region 739:753 the stem region 739:753 We expressed FUT8Δstem mutants, in which the stem region was replaced with glycine/serine linkers, in FUT8-KO HEK293 cells. 36336076 8 42 theme immunoprecipitation 1245:1263 arg1 analysis 1265:1272 immunoprecipitation analysis 1245:1272 immunoprecipitation analysis of another mutant lacking a part of the stem region 1245:1324 Furthermore, immunoprecipitation analysis of another mutant lacking a part of the stem region revealed that the first helix in the FUT8 stem region is critical for multimer formation. 36336076 2 43 theme stem 390:393 arg1 region 395:400 the FUT8 stem region 381:400 the FUT8 stem region 381:400 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 3 44 theme FUT8 567:570 arg1 region 577:582 the FUT8 stem region 563:582 the FUT8 stem region 563:582 Although the stem regions of several glycosyltransferases are involved in the regulation of Golgi localization, the functions of the FUT8 stem region have not been clarified as yet. 36336076 2 45 theme large 334:338 arg1 domain 361:366 its large C-terminal catalytic domain 330:366 its large C-terminal catalytic domain 330:366 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 7 46 theme mutant 1031:1036 arg1 protein 1038:1044 the mutant protein 1027:1044 the mutant protein 1027:1044 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 3 47 theme stem 572:575 arg1 region 577:582 the FUT8 stem region 563:582 the FUT8 stem region 563:582 Although the stem regions of several glycosyltransferases are involved in the regulation of Golgi localization, the functions of the FUT8 stem region have not been clarified as yet. 36336076 9 48 theme stem 1456:1459 arg1 region 1461:1466 the FUT8 stem region 1447:1466 the FUT8 stem region 1447:1466 Our findings demonstrated that the FUT8 stem region is essential for multimer formation but not for catalytic activity, providing insights into how the FUT8 protein matures and functions in mammalian cells. 36336076 9 48 theme stem 1456:1459 arg1 essential 1471:1479 essential 1471:1479 essential 1471:1479 Our findings demonstrated that the FUT8 stem region is essential for multimer formation but not for catalytic activity, providing insights into how the FUT8 protein matures and functions in mammalian cells. 36336076 9 49 theme catalytic 1516:1524 arg1 activity 1526:1533 catalytic activity 1516:1533 catalytic activity 1516:1533 Our findings demonstrated that the FUT8 stem region is essential for multimer formation but not for catalytic activity, providing insights into how the FUT8 protein matures and functions in mammalian cells. 36336076 2 50 theme many 262:265 arg1 FUT8 248:251 FUT8 248:251 FUT8 248:251 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 2 50 theme many 262:265 arg1 glycosyltransferases 273:292 many other glycosyltransferases 262:292 many other glycosyltransferases 262:292 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 2 50 theme many 262:265 arg1 protein 317:323 a type-II membrane protein 298:323 a type-II membrane protein 298:323 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 4 51 theme FUT8 640:643 arg1 region 650:655 the FUT8 stem region 636:655 the FUT8 stem region 636:655 Here, we found that the FUT8 stem region is essential for enzyme oligomerization. 36336076 4 51 theme FUT8 640:643 arg1 essential 660:668 essential 660:668 essential 660:668 Here, we found that the FUT8 stem region is essential for enzyme oligomerization. 36336076 8 52 theme mutant 1285:1290 arg1 analysis 1265:1272 immunoprecipitation analysis 1245:1272 immunoprecipitation analysis of another mutant lacking a part of the stem region 1245:1324 Furthermore, immunoprecipitation analysis of another mutant lacking a part of the stem region revealed that the first helix in the FUT8 stem region is critical for multimer formation. 36336076 8 53 theme region 1319:1324 arg1 part 1302:1305 a part 1300:1305 a part of the stem region 1300:1324 Furthermore, immunoprecipitation analysis of another mutant lacking a part of the stem region revealed that the first helix in the FUT8 stem region is critical for multimer formation. 36336076 1 54 theme physiological 223:235 arg1 processes 237:245 various physiological processes 215:245 various physiological processes 215:245 Alpha-1,6-fucosyltransferase (FUT8) synthesizes core fucose in N-glycans, which plays critical roles in various physiological processes. 36336076 3 55 theme Golgi 526:530 arg1 localization 532:543 Golgi localization 526:543 Golgi localization 526:543 Although the stem regions of several glycosyltransferases are involved in the regulation of Golgi localization, the functions of the FUT8 stem region have not been clarified as yet. 36336076 2 56 attach linked 371:376 arg1 region 395:400 the FUT8 stem region 381:400 the FUT8 stem region 381:400 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 2 56 attach linked 371:376 arg2 domain 361:366 its large C-terminal catalytic domain 330:366 its large C-terminal catalytic domain 330:366 FUT8, as with many other glycosyltransferases, is a type-II membrane protein, and its large C-terminal catalytic domain is linked to the FUT8 stem region, which comprises two α-helices. 36336076 8 57 theme stem 1314:1317 arg1 region 1319:1324 the stem region 1310:1324 the stem region 1310:1324 Furthermore, immunoprecipitation analysis of another mutant lacking a part of the stem region revealed that the first helix in the FUT8 stem region is critical for multimer formation. 36336076 3 58 theme several 463:469 arg1 glycosyltransferases 471:490 several glycosyltransferases 463:490 several glycosyltransferases 463:490 Although the stem regions of several glycosyltransferases are involved in the regulation of Golgi localization, the functions of the FUT8 stem region have not been clarified as yet. 36336076 6 59 theme specific 995:1002 arg1 activity 1004:1011 specific activity 995:1011 specific activity 995:1011 Our immunoprecipitation and native-PAGE analysis showed that FUT8 WT formed a multimer but FUT8Δstem impaired multimer formation in the cells, although the mutants retained specific activity. 36336076 0 60 theme multimer 64:71 arg1 formation 73:81 multimer formation 64:81 multimer formation but not catalytic activity 64:108 The stem region of α1,6-fucosyltransferase FUT8 is required for multimer formation but not catalytic activity. 36336076 1 61 theme various 215:221 arg1 processes 237:245 various physiological processes 215:245 various physiological processes 215:245 Alpha-1,6-fucosyltransferase (FUT8) synthesizes core fucose in N-glycans, which plays critical roles in various physiological processes. 36336076 3 62 theme stem 447:450 arg1 regions 452:458 the stem regions 443:458 the stem regions of several glycosyltransferases 443:490 Although the stem regions of several glycosyltransferases are involved in the regulation of Golgi localization, the functions of the FUT8 stem region have not been clarified as yet. 36336076 4 63 theme stem 645:648 arg1 region 650:655 the FUT8 stem region 636:655 the FUT8 stem region 636:655 Here, we found that the FUT8 stem region is essential for enzyme oligomerization. 36336076 4 63 theme stem 645:648 arg1 essential 660:668 essential 660:668 essential 660:668 Here, we found that the FUT8 stem region is essential for enzyme oligomerization. 36336076 7 64 theme region 1194:1199 arg1 loss 1177:1180 loss 1177:1180 loss of the stem region 1177:1199 In addition, the mutant protein had lower steady-state levels, increased endoplasmic reticulum localization, and a shorter half-life than FUT8 WT, suggesting that loss of the stem region destabilized the FUT8 protein. 36336076 1 65 theme core 159:162 arg1 fucose 164:169 core fucose 159:169 core fucose 159:169 Alpha-1,6-fucosyltransferase (FUT8) synthesizes core fucose in N-glycans, which plays critical roles in various physiological processes. 36336076 8 66 from helix 1350:1354 arg1 region 1373:1378 the FUT8 stem region 1359:1378 the FUT8 stem region 1359:1378 Furthermore, immunoprecipitation analysis of another mutant lacking a part of the stem region revealed that the first helix in the FUT8 stem region is critical for multimer formation. 35772493 8 0 theme SLC35C1-independent 1187:1205 arg1 transport 1207:1215 the SLC35C1-independent transport 1183:1215 the SLC35C1-independent transport 1183:1215 We also found that the SLC35C1-independent transport preferentially utilized GDP-fucose from the salvage pathway over the de novo biogenesis pathway as a source of this substrate. 35772493 1 1 theme SLC35C1 162:168 arg1 gene 170:173 the SLC35C1 gene 158:173 the SLC35C1 gene encoding the Golgi GDP-fucose transporter 158:215 Mutations in the SLC35C1 gene encoding the Golgi GDP-fucose transporter are known to cause leukocyte adhesion deficiency II. 35772493 9 2 theme different 1476:1484 arg1 pathways 1496:1503 different metabolic pathways 1476:1503 different metabolic pathways 1476:1503 Taken together, our results imply that the Golgi systems of GDP-fucose transport discriminate between substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases. 35772493 5 3 theme detectable 814:823 arg1 levels 825:830 low but detectable levels 806:830 low but detectable levels of fucosylation 806:846 We found that cells displayed low but detectable levels of fucosylation in the absence of SLC35C1. 35772493 4 4 theme potential 737:745 arg1 examination 709:719 examination 709:719 examination of fucosylation potential and nucleotide sugar levels 709:773 The resulting cells were cultured in the presence/absence of exogenous fucose and mannose, followed by examination of fucosylation potential and nucleotide sugar levels. 35772493 3 5 from deficient 575:583 arg1 activity 596:603 SLC35C1 activity 588:603 SLC35C1 activity 588:603 To investigate this phenomenon, we developed and characterized a human cell-based model deficient in SLC35C1 activity. 35772493 4 6 theme resulting 610:618 arg1 cells 620:624 The resulting cells 606:624 The resulting cells 606:624 The resulting cells were cultured in the presence/absence of exogenous fucose and mannose, followed by examination of fucosylation potential and nucleotide sugar levels. 35772493 3 7 from activity 596:603 arg1 deficient 575:583 deficient 575:583 deficient 575:583 To investigate this phenomenon, we developed and characterized a human cell-based model deficient in SLC35C1 activity. 35772493 0 8 dep de 125:126 arg1 novo 128:131 novo 128:131 novo 128:131 Incorporation of fucose into glycans independent of the GDP-fucose transporter SLC35C1 preferentially utilizes salvaged over de novo GDP-fucose. 35772493 9 9 theme sugar 1598:1602 arg1 synthases 1604:1612 nucleotide sugar synthases 1587:1612 nucleotide sugar synthases 1587:1612 Taken together, our results imply that the Golgi systems of GDP-fucose transport discriminate between substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases. 35772493 3 10 theme SLC35C1 588:594 arg1 activity 596:603 SLC35C1 activity 588:603 SLC35C1 activity 588:603 To investigate this phenomenon, we developed and characterized a human cell-based model deficient in SLC35C1 activity. 35772493 2 11 theme fucosylation 294:305 arg1 improvement 279:289 improvement 279:289 improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose 279:380 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 6 12 with treatment 961:969 arg1 concentrations 987:1000 millimolar concentrations 976:1000 millimolar concentrations of fucose 976:1010 Strikingly, we show that defects in fucosylation were almost completely reversed upon treatment with millimolar concentrations of fucose. 35772493 0 13 theme de 125:126 arg1 GDP-fucose 133:142 de novo GDP-fucose 125:142 de novo GDP-fucose 125:142 Incorporation of fucose into glycans independent of the GDP-fucose transporter SLC35C1 preferentially utilizes salvaged over de novo GDP-fucose. 35772493 4 14 theme sugar 762:766 arg1 levels 768:773 nucleotide sugar levels 751:773 nucleotide sugar levels 751:773 The resulting cells were cultured in the presence/absence of exogenous fucose and mannose, followed by examination of fucosylation potential and nucleotide sugar levels. 35772493 8 15 used utilized 1232:1239 arg2 transport 1207:1215 the SLC35C1-independent transport 1183:1215 the SLC35C1-independent transport 1183:1215 We also found that the SLC35C1-independent transport preferentially utilized GDP-fucose from the salvage pathway over the de novo biogenesis pathway as a source of this substrate. 35772493 4 16 theme exogenous 667:675 arg1 fucose 677:682 exogenous fucose 667:682 exogenous fucose 667:682 The resulting cells were cultured in the presence/absence of exogenous fucose and mannose, followed by examination of fucosylation potential and nucleotide sugar levels. 35772493 3 17 theme cell-based 558:567 arg1 model 569:573 a human cell-based model 550:573 a human cell-based model deficient in SLC35C1 activity 550:603 To investigate this phenomenon, we developed and characterized a human cell-based model deficient in SLC35C1 activity. 35772493 8 18 theme salvage 1261:1267 arg1 pathway 1269:1275 the salvage pathway 1257:1275 the salvage pathway 1257:1275 We also found that the SLC35C1-independent transport preferentially utilized GDP-fucose from the salvage pathway over the de novo biogenesis pathway as a source of this substrate. 35772493 2 19 theme route 431:435 arg1 existence 395:403 the existence 391:403 the existence 391:403 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 7 20 theme knockout 1148:1155 arg1 cells 1157:1161 these knockout cells 1142:1161 these knockout cells 1142:1161 Furthermore, we show that even if fucose was supplemented at nanomolar concentrations, it was still incorporated into glycans by these knockout cells. 35772493 0 21 dep utilizes 102:109 arg1 salvaged 111:118 salvaged 111:118 utilizes salvaged over de novo GDP-fucose 102:142 Incorporation of fucose into glycans independent of the GDP-fucose transporter SLC35C1 preferentially utilizes salvaged over de novo GDP-fucose. 35772493 2 22 theme SLC35C1-independent 411:429 arg1 route 431:435 an SLC35C1-independent route 408:435 an SLC35C1-independent route of GDP-fucose transport 408:459 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 1 23 from Mutations 145:153 arg1 gene 170:173 the SLC35C1 gene 158:173 the SLC35C1 gene encoding the Golgi GDP-fucose transporter 158:215 Mutations in the SLC35C1 gene encoding the Golgi GDP-fucose transporter are known to cause leukocyte adhesion deficiency II. 35772493 2 24 theme II 340:341 arg1 patients 343:350 leukocyte adhesion deficiency II patients 310:350 leukocyte adhesion deficiency II patients treated with exogenous fucose 310:380 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 1 25 theme Golgi 188:192 arg1 transporter 205:215 the Golgi GDP-fucose transporter 184:215 the Golgi GDP-fucose transporter 184:215 Mutations in the SLC35C1 gene encoding the Golgi GDP-fucose transporter are known to cause leukocyte adhesion deficiency II. 35772493 2 26 theme deficiency 329:338 arg1 II 340:341 leukocyte adhesion deficiency II 310:341 leukocyte adhesion deficiency II patients treated with exogenous fucose 310:380 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 1 27 theme GDP-fucose 194:203 arg1 transporter 205:215 the Golgi GDP-fucose transporter 184:215 the Golgi GDP-fucose transporter 184:215 Mutations in the SLC35C1 gene encoding the Golgi GDP-fucose transporter are known to cause leukocyte adhesion deficiency II. 35772493 9 28 theme Golgi 1387:1391 arg1 systems 1393:1399 the Golgi systems 1383:1399 the Golgi systems of GDP-fucose 1383:1413 Taken together, our results imply that the Golgi systems of GDP-fucose transport discriminate between substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases. 35772493 0 29 dep transporter 67:77 arg1 SLC35C1 79:85 SLC35C1 79:85 the GDP-fucose transporter SLC35C1 52:85 Incorporation of fucose into glycans independent of the GDP-fucose transporter SLC35C1 preferentially utilizes salvaged over de novo GDP-fucose. 35772493 4 30 theme fucose 677:682 arg1 presence/absence 647:662 the presence/absence 643:662 the presence/absence of exogenous fucose and mannose 643:694 The resulting cells were cultured in the presence/absence of exogenous fucose and mannose, followed by examination of fucosylation potential and nucleotide sugar levels. 35772493 0 31 theme fucose 17:22 arg1 Incorporation 0:12 Incorporation 0:12 Incorporation of fucose into glycans independent of the GDP-fucose transporter SLC35C1 0:85 Incorporation of fucose into glycans independent of the GDP-fucose transporter SLC35C1 preferentially utilizes salvaged over de novo GDP-fucose. 35772493 8 32 dep de 1286:1287 arg1 novo 1289:1292 novo 1289:1292 novo 1289:1292 We also found that the SLC35C1-independent transport preferentially utilized GDP-fucose from the salvage pathway over the de novo biogenesis pathway as a source of this substrate. 35772493 4 33 dep cultured 631:638 arg1 followed 697:704 followed 697:704 followed by examination of fucosylation potential and nucleotide sugar levels 697:773 The resulting cells were cultured in the presence/absence of exogenous fucose and mannose, followed by examination of fucosylation potential and nucleotide sugar levels. 35772493 2 34 theme leukocyte 310:318 arg1 II 340:341 leukocyte adhesion deficiency II 310:341 leukocyte adhesion deficiency II patients treated with exogenous fucose 310:380 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 2 35 theme transport 451:459 arg1 route 431:435 an SLC35C1-independent route 408:435 an SLC35C1-independent route of GDP-fucose transport 408:459 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 0 36 theme independent 37:47 arg1 glycans 29:35 glycans 29:35 glycans independent of the GDP-fucose transporter SLC35C1 29:85 Incorporation of fucose into glycans independent of the GDP-fucose transporter SLC35C1 preferentially utilizes salvaged over de novo GDP-fucose. 35772493 4 37 theme mannose 688:694 arg1 presence/absence 647:662 the presence/absence 643:662 the presence/absence of exogenous fucose and mannose 643:694 The resulting cells were cultured in the presence/absence of exogenous fucose and mannose, followed by examination of fucosylation potential and nucleotide sugar levels. 35772493 9 38 theme functional 1523:1532 arg1 connection 1534:1543 a functional connection 1521:1543 a functional connection between nucleotide sugar transporters and nucleotide sugar synthases 1521:1612 Taken together, our results imply that the Golgi systems of GDP-fucose transport discriminate between substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases. 35772493 2 39 theme GDP-fucose 440:449 arg1 transport 451:459 GDP-fucose transport 440:459 GDP-fucose transport 440:459 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 8 40 theme biogenesis 1294:1303 arg1 pathway 1305:1311 the de novo biogenesis pathway 1282:1311 the de novo biogenesis pathway 1282:1311 We also found that the SLC35C1-independent transport preferentially utilized GDP-fucose from the salvage pathway over the de novo biogenesis pathway as a source of this substrate. 35772493 6 41 theme fucose 1005:1010 arg1 concentrations 987:1000 millimolar concentrations 976:1000 millimolar concentrations of fucose 976:1010 Strikingly, we show that defects in fucosylation were almost completely reversed upon treatment with millimolar concentrations of fucose. 35772493 9 42 theme metabolic 1486:1494 arg1 pathways 1496:1503 different metabolic pathways 1476:1503 different metabolic pathways 1476:1503 Taken together, our results imply that the Golgi systems of GDP-fucose transport discriminate between substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases. 35772493 8 43 theme substrate 1333:1341 arg1 source 1318:1323 a source 1316:1323 a source of this substrate 1316:1341 We also found that the SLC35C1-independent transport preferentially utilized GDP-fucose from the salvage pathway over the de novo biogenesis pathway as a source of this substrate. 35772493 8 43 theme substrate 1333:1341 arg1 GDP-fucose 1241:1250 GDP-fucose 1241:1250 GDP-fucose from the salvage pathway over the de novo biogenesis pathway 1241:1311 We also found that the SLC35C1-independent transport preferentially utilized GDP-fucose from the salvage pathway over the de novo biogenesis pathway as a source of this substrate. 35772493 9 44 theme sugar 1564:1568 arg1 transporters 1570:1581 nucleotide sugar transporters 1553:1581 nucleotide sugar transporters 1553:1581 Taken together, our results imply that the Golgi systems of GDP-fucose transport discriminate between substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases. 35772493 5 45 theme fucosylation 835:846 arg1 levels 825:830 low but detectable levels 806:830 low but detectable levels of fucosylation 806:846 We found that cells displayed low but detectable levels of fucosylation in the absence of SLC35C1. 35772493 9 46 theme GDP-fucose 1404:1413 arg1 systems 1393:1399 the Golgi systems 1383:1399 the Golgi systems of GDP-fucose 1383:1413 Taken together, our results imply that the Golgi systems of GDP-fucose transport discriminate between substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases. 35772493 5 47 theme low 806:808 arg1 levels 825:830 low but detectable levels 806:830 low but detectable levels of fucosylation 806:846 We found that cells displayed low but detectable levels of fucosylation in the absence of SLC35C1. 35772493 9 48 theme nucleotide 1553:1562 arg1 transporters 1570:1581 nucleotide sugar transporters 1553:1581 nucleotide sugar transporters 1553:1581 Taken together, our results imply that the Golgi systems of GDP-fucose transport discriminate between substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases. 35772493 2 49 theme exogenous 365:373 arg1 fucose 375:380 exogenous fucose 365:380 exogenous fucose 365:380 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 8 50 theme de 1286:1287 arg1 pathway 1305:1311 the de novo biogenesis pathway 1282:1311 the de novo biogenesis pathway 1282:1311 We also found that the SLC35C1-independent transport preferentially utilized GDP-fucose from the salvage pathway over the de novo biogenesis pathway as a source of this substrate. 35772493 4 51 theme nucleotide 751:760 arg1 levels 768:773 nucleotide sugar levels 751:773 nucleotide sugar levels 751:773 The resulting cells were cultured in the presence/absence of exogenous fucose and mannose, followed by examination of fucosylation potential and nucleotide sugar levels. 35772493 6 52 theme millimolar 976:985 arg1 concentrations 987:1000 millimolar concentrations 976:1000 millimolar concentrations of fucose 976:1010 Strikingly, we show that defects in fucosylation were almost completely reversed upon treatment with millimolar concentrations of fucose. 35772493 7 53 theme nanomolar 1074:1082 arg1 concentrations 1084:1097 nanomolar concentrations 1074:1097 nanomolar concentrations 1074:1097 Furthermore, we show that even if fucose was supplemented at nanomolar concentrations, it was still incorporated into glycans by these knockout cells. 35772493 6 54 from defects 900:906 arg1 fucosylation 911:922 fucosylation 911:922 fucosylation 911:922 Strikingly, we show that defects in fucosylation were almost completely reversed upon treatment with millimolar concentrations of fucose. 35772493 9 55 theme nucleotide 1587:1596 arg1 synthases 1604:1612 nucleotide sugar synthases 1587:1612 nucleotide sugar synthases 1587:1612 Taken together, our results imply that the Golgi systems of GDP-fucose transport discriminate between substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases. 35772493 2 56 theme adhesion 320:327 arg1 II 340:341 leukocyte adhesion deficiency II 310:341 leukocyte adhesion deficiency II patients treated with exogenous fucose 310:380 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 9 57 theme substrate 1446:1454 arg1 pools 1456:1460 substrate pools 1446:1460 substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases 1446:1612 Taken together, our results imply that the Golgi systems of GDP-fucose transport discriminate between substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthases. 35772493 3 58 theme deficient 575:583 arg1 model 569:573 a human cell-based model 550:573 a human cell-based model deficient in SLC35C1 activity 550:603 To investigate this phenomenon, we developed and characterized a human cell-based model deficient in SLC35C1 activity. 35772493 4 59 theme levels 768:773 arg1 examination 709:719 examination 709:719 examination of fucosylation potential and nucleotide sugar levels 709:773 The resulting cells were cultured in the presence/absence of exogenous fucose and mannose, followed by examination of fucosylation potential and nucleotide sugar levels. 35772493 1 60 theme leukocyte 236:244 arg1 II 266:267 leukocyte adhesion deficiency II 236:267 leukocyte adhesion deficiency II 236:267 Mutations in the SLC35C1 gene encoding the Golgi GDP-fucose transporter are known to cause leukocyte adhesion deficiency II. 35772493 0 61 theme transporter 67:77 arg1 independent 37:47 independent 37:47 independent 37:47 Incorporation of fucose into glycans independent of the GDP-fucose transporter SLC35C1 preferentially utilizes salvaged over de novo GDP-fucose. 35772493 4 62 theme fucosylation 724:735 arg1 potential 737:745 fucosylation potential 724:745 fucosylation potential 724:745 The resulting cells were cultured in the presence/absence of exogenous fucose and mannose, followed by examination of fucosylation potential and nucleotide sugar levels. 35772493 2 63 from improvement 279:289 arg1 patients 343:350 leukocyte adhesion deficiency II patients 310:350 leukocyte adhesion deficiency II patients treated with exogenous fucose 310:380 However, improvement of fucosylation in leukocyte adhesion deficiency II patients treated with exogenous fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which remains a mystery. 35772493 1 64 theme adhesion 246:253 arg1 II 266:267 leukocyte adhesion deficiency II 236:267 leukocyte adhesion deficiency II 236:267 Mutations in the SLC35C1 gene encoding the Golgi GDP-fucose transporter are known to cause leukocyte adhesion deficiency II. 35772493 0 65 theme GDP-fucose 56:65 arg1 transporter 67:77 the GDP-fucose transporter SLC35C1 52:85 the GDP-fucose transporter SLC35C1 52:85 Incorporation of fucose into glycans independent of the GDP-fucose transporter SLC35C1 preferentially utilizes salvaged over de novo GDP-fucose. 35772493 8 66 from pathway 1269:1275 arg1 source 1318:1323 a source 1316:1323 a source of this substrate 1316:1341 We also found that the SLC35C1-independent transport preferentially utilized GDP-fucose from the salvage pathway over the de novo biogenesis pathway as a source of this substrate. 35772493 8 66 from pathway 1269:1275 arg1 GDP-fucose 1241:1250 GDP-fucose 1241:1250 GDP-fucose from the salvage pathway over the de novo biogenesis pathway 1241:1311 We also found that the SLC35C1-independent transport preferentially utilized GDP-fucose from the salvage pathway over the de novo biogenesis pathway as a source of this substrate. 35772493 5 67 theme SLC35C1 866:872 arg1 absence 855:861 the absence 851:861 the absence of SLC35C1 851:872 We found that cells displayed low but detectable levels of fucosylation in the absence of SLC35C1. 35772493 1 68 theme deficiency 255:264 arg1 II 266:267 leukocyte adhesion deficiency II 236:267 leukocyte adhesion deficiency II 236:267 Mutations in the SLC35C1 gene encoding the Golgi GDP-fucose transporter are known to cause leukocyte adhesion deficiency II. 35304278 14 0 theme consecutive 2502:2512 arg1 passages 2520:2527 10 consecutive virus passages 2499:2527 10 consecutive virus passages in HEp-2 cells in the presence of this extract 2499:2574 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 7 1 theme anti-respiratory 1266:1281 arg1 virus 1293:1297 anti-respiratory syncytial virus 1266:1297 anti-respiratory syncytial virus (RSV) 1266:1303 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 7 1 theme anti-respiratory 1266:1281 arg1 RSV 1300:1302 RSV 1300:1302 RSV 1300:1302 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 12 2 theme RSV 2203:2205 arg1 infectivity 2217:2227 RSV and HSV-2 infectivity 2203:2227 infectivity 2217:2227 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 4 3 theme STUDY 591:595 arg1 AIM 580:582 AIM 580:582 AIM OF THE STUDY 580:595 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 10 4 theme viruses 1951:1957 arg1 infectivity 1906:1916 infectivity 1906:1916 infectivity of two glycosaminoglycan-binding viruses 1906:1957 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 2 5 theme ethno-medical 357:369 arg1 use 371:373 their ethno-medical use 351:373 their ethno-medical use 351:373 Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. 35304278 17 6 theme water 3089:3093 arg1 extract 3095:3101 the water extract 3085:3101 the water extract of six medicinal plants 3085:3125 CONCLUSIONS Altogether, the water extract of six medicinal plants showed anti-RSV and anti-HSV-2 activities. 35304278 3 7 theme viral 562:566 arg1 infections 568:577 viral infections 562:577 viral infections 562:577 This especially concerns plants with ethnomedical records on their use in treatment of viral infections. 35304278 13 8 from effect 2389:2394 arg1 attachment 2409:2418 the virus attachment 2399:2418 the virus attachment to 2399:2421 The sample exhibited inhibitory effect on the virus attachment to and entry into the cells by directly targeting the viral particles. 35304278 13 8 from effect 2389:2394 arg1 entry 2427:2431 entry 2427:2431 entry into the cells 2427:2446 The sample exhibited inhibitory effect on the virus attachment to and entry into the cells by directly targeting the viral particles. 35304278 4 9 theme antiviral 870:878 arg1 activity 880:887 antiviral activity 870:887 antiviral activity 870:887 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 18 10 theme free 3308:3311 arg1 RSV 3313:3315 free RSV and HSV-2 particles 3308:3335 RSV 3313:3315 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 1 11 from humans 309:314 arg1 treatment 276:284 treatment 276:284 treatment of viral infections in humans 276:314 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 16 12 theme molecular 2972:2980 arg1 mass 2982:2985 molecular mass 2972:2985 molecular mass 2972:2985 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 18 13 theme HSV-2 3321:3325 arg1 particles 3327:3335 free RSV and HSV-2 particles 3308:3335 particles 3327:3335 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 15 14 theme HSV-2 2820:2824 arg1 activity 2826:2833 anti-RSV and HSV-2 activity 2807:2833 anti-RSV and HSV-2 activity 2807:2833 Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. 35304278 10 15 theme acid 1998:2001 arg1 HPIV-2 2011:2016 the sialic acid binding HPIV-2 1987:2016 the sialic acid binding HPIV-2 1987:2016 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 1 16 from infections 295:304 arg1 humans 309:314 humans 309:314 humans 309:314 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 10 17 theme acetate 1813:1819 arg1 extracts 1821:1828 ethyl acetate extracts 1807:1828 ethyl acetate extracts 1807:1828 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 9 18 theme infections 1728:1737 arg1 treatment 1703:1711 treatment 1703:1711 treatment of respiratory infections and muco-cutaneous blisters 1703:1765 RESULTS THPs identified fifteen plants used for treatment of respiratory infections and muco-cutaneous blisters. 35304278 15 19 theme carbohydrate 2851:2862 arg1 content 2864:2870 carbohydrate content 2851:2870 carbohydrate content 2851:2870 Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. 35304278 18 20 theme bark 3199:3202 arg1 studies 3179:3185 Extended studies 3170:3185 Extended studies of the stem bark of E. abyssinica 3170:3219 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 16 21 theme containing 2947:2956 arg1 ingredient 2958:2967 a carbohydrate containing ingredient 2932:2967 a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa 2932:3058 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 6 22 theme oral 1121:1124 arg1 regions 1138:1144 oral and genital regions 1121:1144 oral and genital regions 1121:1144 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 14 23 theme membrane-associated 2643:2661 arg1 attachment 2625:2634 the attachment 2621:2634 the attachment 2621:2634 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 14 23 theme membrane-associated 2643:2661 arg1 protein 2666:2672 viral membrane-associated, G protein 2637:2672 protein 2666:2672 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 9 24 theme muco-cutaneous 1743:1756 arg1 blisters 1758:1765 muco-cutaneous blisters 1743:1765 muco-cutaneous blisters 1743:1765 RESULTS THPs identified fifteen plants used for treatment of respiratory infections and muco-cutaneous blisters. 35304278 4 25 theme health 659:664 arg1 THPs 681:684 THPs 681:684 THPs 681:684 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 4 25 theme health 659:664 arg1 practitioners 666:678 traditional health practitioners 647:678 traditional health practitioners (THPs) 647:685 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 0 26 theme abyssinica 141:150 arg1 bark 157:160 Erythrina abyssinica stem bark 131:160 Erythrina abyssinica stem bark 131:160 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 10 27 theme binding 2003:2009 arg1 HPIV-2 2011:2016 the sialic acid binding HPIV-2 1987:2016 the sialic acid binding HPIV-2 1987:2016 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 11 28 theme abyssinica 2109:2118 arg1 extract 2095:2101 water extract 2089:2101 water extract of E. abyssinica 2089:2118 An activity-guided separation revealed that antiviral component(s) of water extract of E. abyssinica could be precipitated with ethanol. 35304278 10 29 dep RSV 1965:1967 arg1 i.e. 1959:1962 i.e. 1959:1962 i.e. 1959:1962 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 0 30 theme bark 157:160 arg1 studies 120:126 extended studies 111:126 extended studies of Erythrina abyssinica stem bark 111:160 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 15 31 theme E. 2753:2754 arg1 extract 2767:2773 the E. abyssinica extract 2749:2773 the E. abyssinica extract 2749:2773 Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. 35304278 8 32 theme CL-6B 1482:1486 arg1 chromatography 1488:1501 CL-6B chromatography 1482:1501 CL-6B chromatography 1482:1501 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 7 33 theme virus 1372:1376 arg1 activity 1389:1396 anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity 1266:1396 anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells 1266:1414 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 4 34 theme lesions 746:752 arg1 treatment 691:699 treatment 691:699 treatment of respiratory infections and muco-cutaneous lesions 691:752 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 16 35 theme antiviral 2893:2901 arg1 activity 2903:2910 The most pronounced antiviral activity 2873:2910 The most pronounced antiviral activity 2873:2910 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 8 36 dep assay 1574:1578 arg1 the 1553:1555 the 1553:1555 the 1553:1555 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 16 37 theme 410 kDa 3052:3058 arg1 composites 3032:3041 antiviral composites 3022:3041 antiviral composites of up to 410 kDa 3022:3058 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 16 37 theme 410 kDa 3052:3058 arg1 410 kDa 3052:3058 410 kDa 3052:3058 410 kDa 3052:3058 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 7 38 theme anti-human 1347:1356 arg1 virus 1372:1376 anti-human parainfluenza virus 2 1347:1378 anti-human parainfluenza virus 2 (HPIV-2) 1347:1387 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 7 38 theme anti-human 1347:1356 arg1 HPIV-2 1381:1386 HPIV-2 1381:1386 HPIV-2 1381:1386 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 18 39 theme Extended 3170:3177 arg1 studies 3179:3185 Extended studies 3170:3185 Extended studies of the stem bark of E. abyssinica 3170:3219 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 14 40 theme resistant 2591:2599 arg1 variant 2605:2611 a resistant RSV variant 2589:2611 a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop) 2589:2729 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 6 41 from signs 1038:1042 arg1 regions 1138:1144 oral and genital regions 1121:1144 oral and genital regions 1121:1144 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 4 42 theme respiratory 704:714 arg1 infections 716:725 respiratory infections 704:725 respiratory infections 704:725 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 19 43 theme abyssinica 3481:3490 arg1 extract 3492:3498 E. abyssinica extract 3478:3498 E. abyssinica extract 3478:3498 This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions. 35304278 0 44 theme Tanzanian 79:87 arg1 plants 99:104 six Tanzanian medicinal plants 75:104 six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark 75:160 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 17 45 theme anti-RSV 3134:3141 arg1 activities 3158:3167 anti-RSV and anti-HSV-2 activities 3134:3167 anti-RSV and anti-HSV-2 activities 3134:3167 CONCLUSIONS Altogether, the water extract of six medicinal plants showed anti-RSV and anti-HSV-2 activities. 35304278 6 46 from symptoms 1048:1055 arg1 regions 1138:1144 oral and genital regions 1121:1144 oral and genital regions 1121:1144 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 4 47 theme antiviral 778:786 arg1 activity 788:795 their antiviral activity 772:795 their antiviral activity including identification of active components and elucidation of mode of antiviral activity 772:887 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 0 48 theme plants 99:104 arg1 activity 63:70 Anti-respiratory syncytial virus and anti-herpes simplex virus activity 0:70 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 0:161 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 19 49 theme respiratory 3517:3527 arg1 infections 3529:3538 respiratory infections 3517:3538 respiratory infections 3517:3538 This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions. 35304278 18 50 theme antiviral 3232:3240 arg1 components 3242:3251 antiviral components 3232:3251 antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections 3232:3401 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 14 51 theme extract 2568:2574 arg1 presence 2551:2558 the presence 2547:2558 the presence of this extract 2547:2574 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 8 52 theme activity 1530:1537 arg1 mode 1512:1515 the mode 1508:1515 the mode of antiviral activity 1508:1537 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 0 53 theme extended 111:118 arg1 studies 120:126 extended studies 111:126 extended studies of Erythrina abyssinica stem bark 111:160 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 18 54 theme abyssinica 3210:3219 arg1 bark 3199:3202 the stem bark 3190:3202 the stem bark of E. abyssinica 3190:3219 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 6 55 theme blisters 1109:1116 arg1 signs 1038:1042 signs 1038:1042 signs 1038:1042 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 6 55 theme blisters 1109:1116 arg1 symptoms 1048:1055 symptoms 1048:1055 symptoms 1048:1055 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 2 56 theme antiviral 458:466 arg1 drugs 468:472 novel candidate antiviral drugs 442:472 novel candidate antiviral drugs 442:472 Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. 35304278 19 57 theme infections 3529:3538 arg1 treatment 3504:3512 treatment 3504:3512 treatment of respiratory infections and herpetic lesions 3504:3559 This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions. 35304278 8 58 theme antiviral 1630:1638 arg1 extract 1646:1652 antiviral plant extract 1630:1652 antiviral plant extract 1630:1652 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 2 59 theme important 389:397 arg1 source 399:404 an important source 386:404 an important source of compounds for the development of novel candidate antiviral drugs 386:472 Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. 35304278 0 60 theme Anti-respiratory 0:15 arg1 virus 27:31 Anti-respiratory syncytial virus 0:31 Anti-respiratory syncytial virus 0:31 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 1 61 theme viral 289:293 arg1 infections 295:304 viral infections 289:304 viral infections in humans 289:314 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 5 62 theme Tanzania 975:982 arg1 region 965:970 the Kagera region 954:970 the Kagera region of Tanzania 954:982 MATERIALS AND METHODS The ethno-medical survey was performed in the Kagera region of Tanzania. 35304278 6 63 theme watery 1087:1092 arg1 blisters 1109:1116 watery muco-cutaneous blisters 1087:1116 watery muco-cutaneous blisters 1087:1116 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 2 64 theme novel 442:446 arg1 drugs 468:472 novel candidate antiviral drugs 442:472 novel candidate antiviral drugs 442:472 Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. 35304278 8 65 theme time-of-addition 1557:1572 arg1 assay 1574:1578 time-of-addition assay 1557:1578 time-of-addition assay 1557:1578 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 18 66 theme particles 3327:3335 arg1 feature 3340:3346 a feature 3338:3346 a feature of importance 3338:3360 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 18 66 theme particles 3327:3335 arg1 infectivity 3293:3303 infectivity 3293:3303 infectivity of free RSV and HSV-2 particles 3293:3335 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 6 67 from blisters 1109:1116 arg1 regions 1138:1144 oral and genital regions 1121:1144 oral and genital regions 1121:1144 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 12 68 theme IC50 2252:2255 arg1 values 2257:2262 IC50 values 2252:2262 IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) 2252:2341 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 14 69 from residue 2708:2714 arg1 codon 2688:2692 a stop codon 2681:2692 a stop codon at amino acid residue 33 (Leu33stop) 2681:2729 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 0 70 theme virus 27:31 arg1 activity 63:70 Anti-respiratory syncytial virus and anti-herpes simplex virus activity 0:70 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 0:161 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 17 71 dep CONCLUSIONS 3061:3071 arg1 showed 3127:3132 showed 3127:3132 showed anti-RSV and anti-HSV-2 activities 3127:3167 CONCLUSIONS Altogether, the water extract of six medicinal plants showed anti-RSV and anti-HSV-2 activities. 35304278 6 72 theme infections 1072:1081 arg1 signs 1038:1042 signs 1038:1042 signs 1038:1042 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 6 72 theme infections 1072:1081 arg1 symptoms 1048:1055 symptoms 1048:1055 symptoms 1048:1055 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 10 73 theme ethyl 1807:1811 arg1 extracts 1821:1828 ethyl acetate extracts 1807:1828 ethyl acetate extracts 1807:1828 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 6 74 theme respiratory 1060:1070 arg1 infections 1072:1081 respiratory infections 1060:1081 respiratory infections 1060:1081 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 12 75 theme HSV-2 2211:2215 arg1 infectivity 2217:2227 RSV and HSV-2 infectivity 2203:2227 infectivity 2217:2227 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 0 76 theme anti-herpes 37:47 arg1 virus 57:61 anti-herpes simplex virus 37:61 anti-herpes simplex virus 37:61 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 14 77 theme RSV 2601:2603 arg1 variant 2605:2611 a resistant RSV variant 2589:2611 a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop) 2589:2729 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 7 78 theme virus 1326:1330 arg1 activity 1389:1396 anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity 1266:1396 anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells 1266:1414 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 10 79 theme abyssinica 1874:1883 arg1 bark 1890:1893 Erythrina abyssinica stem bark 1864:1893 Erythrina abyssinica stem bark 1864:1893 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 5 80 dep MATERIALS 890:898 arg1 performed 941:949 performed 941:949 was performed in the Kagera region of Tanzania 937:982 MATERIALS AND METHODS The ethno-medical survey was performed in the Kagera region of Tanzania. 35304278 0 81 theme virus 57:61 arg1 activity 63:70 Anti-respiratory syncytial virus and anti-herpes simplex virus activity 0:70 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 0:161 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 16 82 theme carbohydrate 2934:2945 arg1 ingredient 2958:2967 a carbohydrate containing ingredient 2932:2967 a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa 2932:3058 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 3 83 with plants 500:505 arg1 records 525:531 ethnomedical records 512:531 ethnomedical records 512:531 This especially concerns plants with ethnomedical records on their use in treatment of viral infections. 35304278 7 84 theme anti-herpes 1306:1316 arg1 virus 1326:1330 anti-herpes simplex virus 2 1306:1332 anti-herpes simplex virus 2 (HSV-2) 1306:1340 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 7 84 theme anti-herpes 1306:1316 arg1 HSV-2 1335:1339 HSV-2 1335:1339 HSV-2 1335:1339 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 8 85 theme virus 1602:1606 arg1 variants 1608:1615 the virus variants 1598:1615 the virus variants resistant to antiviral plant extract 1598:1652 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 17 86 theme anti-HSV-2 3147:3156 arg1 activities 3158:3167 anti-RSV and anti-HSV-2 activities 3134:3167 anti-RSV and anti-HSV-2 activities 3134:3167 CONCLUSIONS Altogether, the water extract of six medicinal plants showed anti-RSV and anti-HSV-2 activities. 35304278 1 87 theme antiviral 239:247 arg1 drug 249:252 no antiviral drug 236:252 no antiviral drug 236:252 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 1 87 theme antiviral 239:247 arg1 RELEVANCE 184:192 ETHNOPHARMACOLOGICAL RELEVANCE 163:192 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses 163:233 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 8 88 theme resistant 1617:1625 arg1 variants 1608:1615 the virus variants 1598:1615 the virus variants resistant to antiviral plant extract 1598:1652 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 4 89 theme components 832:841 arg1 elucidation 847:857 elucidation 847:857 elucidation of mode of antiviral activity 847:887 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 4 89 theme components 832:841 arg1 identification 807:820 identification 807:820 identification of active components 807:841 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 14 90 theme virus 2514:2518 arg1 passages 2520:2527 10 consecutive virus passages 2499:2527 10 consecutive virus passages in HEp-2 cells in the presence of this extract 2499:2574 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 18 91 theme stem 3194:3197 arg1 bark 3199:3202 the stem bark 3190:3202 the stem bark of E. abyssinica 3190:3219 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 6 92 theme genital 1130:1136 arg1 regions 1138:1144 oral and genital regions 1121:1144 oral and genital regions 1121:1144 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 16 93 theme mass 2982:2985 arg1 ingredient 2958:2967 a carbohydrate containing ingredient 2932:2967 a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa 2932:3058 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 4 94 theme medicinal 622:630 arg1 plants 632:637 medicinal plants 622:637 medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions 622:752 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 15 95 theme CL-6B 2780:2784 arg1 column 2786:2791 a CL-6B column 2778:2791 a CL-6B column 2778:2791 Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. 35304278 11 96 with precipitated 2129:2140 arg1 ethanol 2147:2153 ethanol 2147:2153 ethanol 2147:2153 An activity-guided separation revealed that antiviral component(s) of water extract of E. abyssinica could be precipitated with ethanol. 35304278 7 97 theme syncytial 1283:1291 arg1 virus 1293:1297 anti-respiratory syncytial virus 1266:1297 anti-respiratory syncytial virus (RSV) 1266:1303 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 7 97 theme syncytial 1283:1291 arg1 RSV 1300:1302 RSV 1300:1302 RSV 1300:1302 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 10 98 theme glycosaminoglycan-binding 1925:1949 arg1 viruses 1951:1957 two glycosaminoglycan-binding viruses 1921:1957 two glycosaminoglycan-binding viruses 1921:1957 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 4 99 theme mode 862:865 arg1 elucidation 847:857 elucidation 847:857 elucidation of mode of antiviral activity 847:887 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 4 99 theme mode 862:865 arg1 identification 807:820 identification 807:820 identification of active components 807:841 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 16 100 theme pronounced 2882:2891 arg1 activity 2903:2910 The most pronounced antiviral activity 2873:2910 The most pronounced antiviral activity 2873:2910 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 19 101 theme extract 3492:3498 arg1 use 3471:3473 the use 3467:3473 the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions 3467:3559 This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions. 35304278 15 102 theme abyssinica 2756:2765 arg1 extract 2767:2773 the E. abyssinica extract 2749:2773 the E. abyssinica extract 2749:2773 Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. 35304278 3 103 from use 542:544 arg1 treatment 549:557 treatment 549:557 treatment of viral infections 549:577 This especially concerns plants with ethnomedical records on their use in treatment of viral infections. 35304278 11 104 theme activity-guided 2022:2036 arg1 separation 2038:2047 An activity-guided separation 2019:2047 An activity-guided separation 2019:2047 An activity-guided separation revealed that antiviral component(s) of water extract of E. abyssinica could be precipitated with ethanol. 35304278 18 105 theme topical 3365:3371 arg1 treatment 3373:3381 topical treatment 3365:3381 topical treatment of these infections 3365:3401 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 19 106 theme E. 3478:3479 arg1 extract 3492:3498 E. abyssinica extract 3478:3498 E. abyssinica extract 3478:3498 This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions. 35304278 15 107 theme extract 2767:2773 arg1 Fractionation 2732:2744 Fractionation 2732:2744 Fractionation of the E. abyssinica extract on a CL-6B column 2732:2791 Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. 35304278 19 108 theme herpetic 3544:3551 arg1 lesions 3553:3559 herpetic lesions 3544:3559 herpetic lesions 3544:3559 This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions. 35304278 1 109 theme few 205:207 arg1 viruses 227:233 few highly pathogenic viruses 205:233 few highly pathogenic viruses 205:233 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 12 110 theme selectivity 2318:2328 arg1 0.14 μg/ml 2306:2315 0.14 μg/ml 2306:2315 0.14 μg/ml (selectivity index >7143) 2306:2341 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 12 110 theme selectivity 2318:2328 arg1 index 2330:2334 selectivity index >7143 2318:2340 selectivity index >7143 2318:2340 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 4 111 theme activity 880:887 arg1 mode 862:865 mode 862:865 mode of antiviral activity 862:887 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 10 112 theme sialic 1991:1996 arg1 HPIV-2 2011:2016 the sialic acid binding HPIV-2 1987:2016 the sialic acid binding HPIV-2 1987:2016 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 0 113 theme Erythrina 131:139 arg1 bark 157:160 Erythrina abyssinica stem bark 131:160 Erythrina abyssinica stem bark 131:160 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 0 114 with plants 99:104 arg1 studies 120:126 extended studies 111:126 extended studies of Erythrina abyssinica stem bark 111:160 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 2 115 theme Plant 317:321 arg1 extracts 323:330 Plant extracts 317:330 Plant extracts 317:330 Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. 35304278 1 116 theme pathogenic 216:225 arg1 viruses 227:233 few highly pathogenic viruses 205:233 few highly pathogenic viruses 205:233 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 19 117 theme lesions 3553:3559 arg1 treatment 3504:3512 treatment 3504:3512 treatment of respiratory infections and herpetic lesions 3504:3559 This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions. 35304278 11 118 theme extract 2095:2101 arg1 s 2083:2083 antiviral component(s) 2063:2084 antiviral component(s) of water extract of E. abyssinica 2063:2118 An activity-guided separation revealed that antiviral component(s) of water extract of E. abyssinica could be precipitated with ethanol. 35304278 8 119 theme ethanol 1456:1462 arg1 precipitation 1464:1476 ethanol precipitation 1456:1476 ethanol precipitation 1456:1476 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 7 120 theme cultured 1401:1408 arg1 cells 1410:1414 cultured cells 1401:1414 cultured cells 1401:1414 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 14 121 theme amino 2697:2701 arg1 residue 2708:2714 amino acid residue 33 2697:2717 amino acid residue 33 (Leu33stop) 2697:2729 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 14 121 theme amino 2697:2701 arg1 Leu33stop 2720:2728 Leu33stop 2720:2728 Leu33stop 2720:2728 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 0 122 theme stem 152:155 arg1 bark 157:160 Erythrina abyssinica stem bark 131:160 Erythrina abyssinica stem bark 131:160 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 9 123 theme respiratory 1716:1726 arg1 infections 1728:1737 respiratory infections 1716:1737 respiratory infections 1716:1737 RESULTS THPs identified fifteen plants used for treatment of respiratory infections and muco-cutaneous blisters. 35304278 14 124 theme viral 2637:2641 arg1 attachment 2625:2634 the attachment 2621:2634 the attachment 2621:2634 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 14 124 theme viral 2637:2641 arg1 protein 2666:2672 viral membrane-associated, G protein 2637:2672 protein 2666:2672 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 9 125 theme blisters 1758:1765 arg1 treatment 1703:1711 treatment 1703:1711 treatment of respiratory infections and muco-cutaneous blisters 1703:1765 RESULTS THPs identified fifteen plants used for treatment of respiratory infections and muco-cutaneous blisters. 35304278 4 126 theme traditional 647:657 arg1 THPs 681:684 THPs 681:684 THPs 681:684 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 4 126 theme traditional 647:657 arg1 practitioners 666:678 traditional health practitioners 647:678 traditional health practitioners (THPs) 647:685 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 13 127 theme viral 2474:2478 arg1 particles 2480:2488 the viral particles 2470:2488 the viral particles 2470:2488 The sample exhibited inhibitory effect on the virus attachment to and entry into the cells by directly targeting the viral particles. 35304278 17 128 theme plants 3120:3125 arg1 extract 3095:3101 the water extract 3085:3101 the water extract of six medicinal plants 3085:3125 CONCLUSIONS Altogether, the water extract of six medicinal plants showed anti-RSV and anti-HSV-2 activities. 35304278 1 129 from treatment 276:284 arg1 humans 309:314 humans 309:314 humans 309:314 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 19 130 theme ethno-medical 3430:3442 arg1 information 3444:3454 ethno-medical information 3430:3454 ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions 3430:3559 This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions. 35304278 4 131 theme infections 716:725 arg1 treatment 691:699 treatment 691:699 treatment of respiratory infections and muco-cutaneous lesions 691:752 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 6 132 from infections 1072:1081 arg1 regions 1138:1144 oral and genital regions 1121:1144 oral and genital regions 1121:1144 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 15 133 theme anti-RSV 2807:2814 arg1 activity 2826:2833 anti-RSV and HSV-2 activity 2807:2833 anti-RSV and HSV-2 activity 2807:2833 Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. 35304278 10 134 theme Erythrina 1864:1872 arg1 bark 1890:1893 Erythrina abyssinica stem bark 1864:1893 Erythrina abyssinica stem bark 1864:1893 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 5 135 theme Kagera 958:963 arg1 region 965:970 the Kagera region 954:970 the Kagera region of Tanzania 954:982 MATERIALS AND METHODS The ethno-medical survey was performed in the Kagera region of Tanzania. 35304278 3 136 theme infections 568:577 arg1 treatment 549:557 treatment 549:557 treatment of viral infections 549:577 This especially concerns plants with ethnomedical records on their use in treatment of viral infections. 35304278 6 137 theme symptoms 1048:1055 arg1 treatment 1025:1033 treatment 1025:1033 treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions 1025:1144 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 18 138 theme RSV 3313:3315 arg1 feature 3340:3346 a feature 3338:3346 a feature of importance 3338:3360 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 18 138 theme RSV 3313:3315 arg1 infectivity 3293:3303 infectivity 3293:3303 infectivity of free RSV and HSV-2 particles 3293:3335 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 4 139 theme muco-cutaneous 731:744 arg1 lesions 746:752 muco-cutaneous lesions 731:752 muco-cutaneous lesions 731:752 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 16 140 theme antiviral 3022:3030 arg1 composites 3032:3041 antiviral composites 3022:3041 antiviral composites of up to 410 kDa 3022:3058 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 16 140 theme antiviral 3022:3030 arg1 410 kDa 3052:3058 410 kDa 3052:3058 410 kDa 3052:3058 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 11 141 theme water 2089:2093 arg1 extract 2095:2101 water extract 2089:2101 water extract of E. abyssinica 2089:2118 An activity-guided separation revealed that antiviral component(s) of water extract of E. abyssinica could be precipitated with ethanol. 35304278 10 142 theme plants 1847:1852 arg1 six 1834:1836 six 1834:1836 six 1834:1836 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 10 142 theme plants 1847:1852 arg1 plants 1847:1852 these plants 1841:1852 these plants including Erythrina abyssinica stem bark 1841:1893 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 10 142 theme plants 1847:1852 arg1 bark 1890:1893 Erythrina abyssinica stem bark 1864:1893 Erythrina abyssinica stem bark 1864:1893 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 5 143 theme ethno-medical 916:928 arg1 survey 930:935 The ethno-medical survey 912:935 The ethno-medical survey 912:935 MATERIALS AND METHODS The ethno-medical survey was performed in the Kagera region of Tanzania. 35304278 6 144 theme signs 1038:1042 arg1 treatment 1025:1033 treatment 1025:1033 treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions 1025:1144 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 12 145 theme 0.14 μg/ml 2306:2315 arg1 values 2257:2262 IC50 values 2252:2262 IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) 2252:2341 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 7 146 theme parainfluenza 1358:1370 arg1 virus 1372:1376 anti-human parainfluenza virus 2 1347:1378 anti-human parainfluenza virus 2 (HPIV-2) 1347:1387 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 7 146 theme parainfluenza 1358:1370 arg1 HPIV-2 1381:1386 HPIV-2 1381:1386 HPIV-2 1381:1386 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 0 147 theme medicinal 89:97 arg1 plants 99:104 six Tanzanian medicinal plants 75:104 six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark 75:160 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 1 148 theme ETHNOPHARMACOLOGICAL 163:182 arg1 drug 249:252 no antiviral drug 236:252 no antiviral drug 236:252 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 1 148 theme ETHNOPHARMACOLOGICAL 163:182 arg1 RELEVANCE 184:192 ETHNOPHARMACOLOGICAL RELEVANCE 163:192 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses 163:233 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 8 149 theme antiviral 1520:1528 arg1 activity 1530:1537 antiviral activity 1520:1537 antiviral activity 1520:1537 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 12 150 with cells 2241:2245 arg1 values 2257:2262 IC50 values 2252:2262 IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) 2252:2341 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 11 151 theme component 2073:2081 arg1 s 2083:2083 antiviral component(s) 2063:2084 antiviral component(s) of water extract of E. abyssinica 2063:2118 An activity-guided separation revealed that antiviral component(s) of water extract of E. abyssinica could be precipitated with ethanol. 35304278 18 152 theme infections 3392:3401 arg1 treatment 3373:3381 topical treatment 3365:3381 topical treatment of these infections 3365:3401 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 15 153 from Fractionation 2732:2744 arg1 column 2786:2791 a CL-6B column 2778:2791 a CL-6B column 2778:2791 Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. 35304278 12 154 theme 2.1 μg/ml 2267:2275 arg1 values 2257:2262 IC50 values 2252:2262 IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) 2252:2341 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 0 155 theme syncytial 17:25 arg1 virus 27:31 Anti-respiratory syncytial virus 0:31 Anti-respiratory syncytial virus 0:31 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 12 156 theme selectivity 2278:2288 arg1 2.1 μg/ml 2267:2275 2.1 μg/ml 2267:2275 2.1 μg/ml (selectivity index >476) 2267:2300 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 12 156 theme selectivity 2278:2288 arg1 index 2290:2294 selectivity index >476 2278:2299 selectivity index >476 2278:2299 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 6 157 theme muco-cutaneous 1094:1107 arg1 blisters 1109:1116 watery muco-cutaneous blisters 1087:1116 watery muco-cutaneous blisters 1087:1116 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 2 158 theme candidate 448:456 arg1 drugs 468:472 novel candidate antiviral drugs 442:472 novel candidate antiviral drugs 442:472 Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. 35304278 12 159 theme cultured 2232:2239 arg1 cells 2241:2245 cultured cells 2232:2245 cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) 2232:2341 This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. 35304278 11 160 theme antiviral 2063:2071 arg1 s 2083:2083 antiviral component(s) 2063:2084 antiviral component(s) of water extract of E. abyssinica 2063:2118 An activity-guided separation revealed that antiviral component(s) of water extract of E. abyssinica could be precipitated with ethanol. 35304278 16 161 theme <5 kDa 2990:2995 arg1 mass 2982:2985 molecular mass 2972:2985 molecular mass 2972:2985 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 1 162 theme infections 295:304 arg1 treatment 276:284 treatment 276:284 treatment of viral infections in humans 276:314 ETHNOPHARMACOLOGICAL RELEVANCE Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. 35304278 17 163 theme medicinal 3110:3118 arg1 plants 3120:3125 six medicinal plants 3106:3125 six medicinal plants 3106:3125 CONCLUSIONS Altogether, the water extract of six medicinal plants showed anti-RSV and anti-HSV-2 activities. 35304278 14 164 theme stop 2683:2686 arg1 codon 2688:2692 a stop codon 2681:2692 a stop codon at amino acid residue 33 (Leu33stop) 2681:2729 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 0 165 theme simplex 49:55 arg1 virus 57:61 anti-herpes simplex virus 37:61 anti-herpes simplex virus 37:61 Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark. 35304278 13 166 theme virus 2403:2407 arg1 attachment 2409:2418 the virus attachment 2399:2418 the virus attachment to 2399:2421 The sample exhibited inhibitory effect on the virus attachment to and entry into the cells by directly targeting the viral particles. 35304278 7 167 from activity 1389:1396 arg1 cells 1410:1414 cultured cells 1401:1414 cultured cells 1401:1414 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 7 168 theme simplex 1318:1324 arg1 virus 1326:1330 anti-herpes simplex virus 2 1306:1332 anti-herpes simplex virus 2 (HSV-2) 1306:1340 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 7 168 theme simplex 1318:1324 arg1 HSV-2 1335:1339 HSV-2 1335:1339 HSV-2 1335:1339 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 10 169 theme stem 1885:1888 arg1 bark 1890:1893 Erythrina abyssinica stem bark 1864:1893 Erythrina abyssinica stem bark 1864:1893 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 2 170 theme compounds 409:417 arg1 source 399:404 an important source 386:404 an important source of compounds for the development of novel candidate antiviral drugs 386:472 Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. 35304278 14 171 theme acid 2703:2706 arg1 residue 2708:2714 amino acid residue 33 2697:2717 amino acid residue 33 (Leu33stop) 2697:2729 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 14 171 theme acid 2703:2706 arg1 Leu33stop 2720:2728 Leu33stop 2720:2728 Leu33stop 2720:2728 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 2 172 theme drugs 468:472 arg1 development 427:437 the development 423:437 the development of novel candidate antiviral drugs 423:472 Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. 35304278 14 173 dep protein 2666:2672 arg1 G 2664:2664 viral membrane-associated, G protein 2637:2672 G 2664:2664 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 14 174 from passages 2520:2527 arg1 HEp-2 cells 2532:2542 HEp-2 cells 2532:2542 HEp-2 cells in the presence of this extract 2532:2574 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 3 175 theme ethnomedical 512:523 arg1 records 525:531 ethnomedical records 512:531 ethnomedical records 512:531 This especially concerns plants with ethnomedical records on their use in treatment of viral infections. 35304278 18 176 theme importance 3351:3360 arg1 feature 3340:3346 a feature 3338:3346 a feature of importance 3338:3360 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 18 176 theme importance 3351:3360 arg1 infectivity 3293:3303 infectivity 3293:3303 infectivity of free RSV and HSV-2 particles 3293:3335 Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. 35304278 13 177 theme inhibitory 2378:2387 arg1 effect 2389:2394 inhibitory effect 2378:2394 inhibitory effect on the virus attachment to and entry into the cells 2378:2446 The sample exhibited inhibitory effect on the virus attachment to and entry into the cells by directly targeting the viral particles. 35304278 14 178 from HEp-2 cells 2532:2542 arg1 presence 2551:2558 the presence 2547:2558 the presence of this extract 2547:2574 Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). 35304278 8 179 theme Antiviral 1417:1425 arg1 components 1427:1436 Antiviral components 1417:1436 Antiviral components 1417:1436 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 10 180 theme water 1772:1776 arg1 extract 1778:1784 The water extract 1768:1784 The water extract 1768:1784 The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. 35304278 9 181 theme RESULTS 1655:1661 arg1 THPs 1663:1666 RESULTS THPs 1655:1666 RESULTS THPs 1655:1666 RESULTS THPs identified fifteen plants used for treatment of respiratory infections and muco-cutaneous blisters. 35304278 7 182 theme virus 1293:1297 arg1 activity 1389:1396 anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity 1266:1396 anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells 1266:1414 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35304278 8 183 theme plant 1640:1644 arg1 extract 1646:1652 antiviral plant extract 1630:1652 antiviral plant extract 1630:1652 Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. 35304278 16 184 dep 410 kDa 3052:3058 arg1 to 3049:3050 to 3049:3050 to 3049:3050 The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. 35304278 4 185 theme active 825:830 arg1 components 832:841 active components 825:841 active components 825:841 AIM OF THE STUDY To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. 35304278 6 186 from regions 1138:1144 arg1 signs 1038:1042 signs 1038:1042 signs 1038:1042 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 6 186 from regions 1138:1144 arg1 symptoms 1048:1055 symptoms 1048:1055 symptoms 1048:1055 The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. 35304278 7 187 theme ethyl 1212:1216 arg1 acetate 1218:1224 ethyl acetate 1212:1224 ethyl acetate 1212:1224 The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. 35959165 10 0 theme X-ray 1518:1522 arg1 diffractogram 1524:1536 X-ray diffractogram 1518:1536 X-ray diffractogram 1518:1536 Semi-crystalline nature and thermal stability were confirmed by X-ray diffractogram and differential scanning calorimetry analysis, respectively. 35959165 11 1 theme concentration-dependent 1649:1671 arg1 manner 1673:1678 a concentration-dependent manner 1647:1678 a concentration-dependent manner 1647:1678 The EPS further shows antioxidant potential in a concentration-dependent manner. 35959165 12 2 theme pharmaceutical 1797:1810 arg1 industries 1812:1821 food, and pharmaceutical industries 1787:1821 food, and pharmaceutical industries 1787:1821 It can form a stable emulsion against different edible oil that makes it promising alternative for use in food, and pharmaceutical industries. 35959165 8 3 theme compact 1034:1040 arg1 lumps 1053:1057 compact, irregular lumps 1034:1057 compact, irregular lumps 1034:1057 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 1 4 theme responsible 163:173 arg1 bacteria 154:161 bacteria 154:161 bacteria responsible for teeth blackening 154:194 Enterobacter ludwigii is an oral growing bacteria responsible for teeth blackening. 35959165 7 5 theme different 835:843 arg1 galactose 879:887 galactose 879:887 galactose (4.25%) 879:895 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 5 theme different 835:843 arg1 mannose 898:904 mannose 898:904 mannose (4.04%) 898:912 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 5 theme different 835:843 arg1 monosaccharides 845:859 different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) 835:932 different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) 835:932 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 5 theme different 835:843 arg1 glucose 861:867 glucose 861:867 glucose (16.91%) 861:876 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 5 theme different 835:843 arg1 xylose 919:924 xylose 919:924 xylose (8.06%) 919:932 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 3 6 theme formaldehyde-sodium 337:355 arg1 method 367:372 the formaldehyde-sodium hydroxide method 333:372 the formaldehyde-sodium hydroxide method 333:372 The exopolysaccharide (EPS) cluster associated with biofilm formation was isolated using ethanol precipitation and the formaldehyde-sodium hydroxide method. 35959165 9 7 theme different 1265:1273 arg1 solvents 1286:1293 different deuterated solvents 1265:1293 different deuterated solvents (Protic and aprotic solvents for exchangeable protons) 1265:1348 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 12 8 theme different 1719:1727 arg1 oil 1736:1738 different edible oil 1719:1738 different edible oil 1719:1738 It can form a stable emulsion against different edible oil that makes it promising alternative for use in food, and pharmaceutical industries. 35959165 4 9 theme UV 427:428 arg1 spectroscopy 430:441 UV spectroscopy 427:441 UV spectroscopy 427:441 The chemical characterization of EPS was done using UV spectroscopy, Fourier transforms infrared spectroscopy, and gas chromatography-mass spectrometry. 35959165 8 10 theme stacked 1063:1069 arg1 flakes 1071:1076 stacked flakes 1063:1076 stacked flakes of polysaccharides 1063:1095 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 7 11 theme monosaccharides 845:859 arg1 presence 823:830 the presence 819:830 the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) 819:932 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 11 theme monosaccharides 845:859 arg1 components 947:956 the major components 937:956 the major components of EPS 937:963 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 9 12 theme 13C 1213:1215 arg1 NMR 1208:1210 1H NMR 1205:1210 1H NMR 1205:1210 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 12 theme 13C 1213:1215 arg1 NMR 1217:1219 13C NMR 1213:1219 13C NMR 1213:1219 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 13 theme spectroscopy 1180:1191 arg1 techniques 1193:1202 Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) 1147:1258 Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) 1147:1258 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 10 14 theme calorimetry 1564:1574 arg1 analysis 1576:1583 X-ray diffractogram and differential scanning calorimetry analysis 1518:1583 X-ray diffractogram and differential scanning calorimetry analysis 1518:1583 Semi-crystalline nature and thermal stability were confirmed by X-ray diffractogram and differential scanning calorimetry analysis, respectively. 35959165 9 15 theme 1H-13C 1234:1239 arg1 NMR 1208:1210 1H NMR 1205:1210 1H NMR 1205:1210 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 15 theme 1H-13C 1234:1239 arg1 HSQC 1241:1244 1H-13C HSQC 1234:1244 1H-13C HSQC 1234:1244 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 3 16 theme exopolysaccharide 222:238 arg1 cluster 246:252 The exopolysaccharide (EPS) cluster 218:252 The exopolysaccharide (EPS) cluster associated with biofilm formation 218:286 The exopolysaccharide (EPS) cluster associated with biofilm formation was isolated using ethanol precipitation and the formaldehyde-sodium hydroxide method. 35959165 9 17 theme 1H 1205:1206 arg1 NMR 1208:1210 1H NMR 1205:1210 1H NMR 1205:1210 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 17 theme 1H 1205:1206 arg1 NMR 1217:1219 13C NMR 1213:1219 13C NMR 1213:1219 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 17 theme 1H 1205:1206 arg1 COSY 1228:1231 1H-1H COSY 1222:1231 1H-1H COSY 1222:1231 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 17 theme 1H 1205:1206 arg1 HSQC 1241:1244 1H-13C HSQC 1234:1244 1H-13C HSQC 1234:1244 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 17 theme 1H 1205:1206 arg1 HMBC 1254:1257 1H-13C HMBC 1247:1257 1H-13C HMBC 1247:1257 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 6 18 theme polysaccharide 774:787 arg1 composition 789:799 polysaccharide composition 774:799 polysaccharide composition 774:799 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 5 19 theme spectroscopy 552:563 arg1 analysis 571:578 Energy-dispersive X-ray spectroscopy (EDS) analysis 528:578 Energy-dispersive X-ray spectroscopy (EDS) analysis of EPS 528:585 Energy-dispersive X-ray spectroscopy (EDS) analysis of EPS has revealed the presence of carbon > boron > nitrogen > phosphorous > calcium > sulfur > iron > potassium > magnesium. 35959165 10 20 theme scanning 1555:1562 arg1 calorimetry 1564:1574 differential scanning calorimetry 1542:1574 differential scanning calorimetry 1542:1574 Semi-crystalline nature and thermal stability were confirmed by X-ray diffractogram and differential scanning calorimetry analysis, respectively. 35959165 13 21 theme supplementary 1878:1890 arg1 material 1892:1899 supplementary material 1878:1899 supplementary material available at 10.1007/s13205-022-03279-z 1878:1939 Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03279-z. 35959165 8 22 theme polysaccharides 1081:1095 arg1 lumps 1053:1057 compact, irregular lumps 1034:1057 compact, irregular lumps 1034:1057 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 8 22 theme polysaccharides 1081:1095 arg1 structure 1023:1031 three-dimensional structure 1005:1031 three-dimensional structure 1005:1031 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 8 22 theme polysaccharides 1081:1095 arg1 flakes 1071:1076 stacked flakes 1063:1076 stacked flakes of polysaccharides 1063:1095 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 8 23 theme three-dimensional 1005:1021 arg1 structure 1023:1031 three-dimensional structure 1005:1031 three-dimensional structure 1005:1031 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 13 24 from 10.1007/s13205-022-03279-z 1914:1939 arg1 available 1901:1909 available 1901:1909 available 1901:1909 Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03279-z. 35959165 10 25 theme thermal 1482:1488 arg1 stability 1490:1498 thermal stability 1482:1498 thermal stability 1482:1498 Semi-crystalline nature and thermal stability were confirmed by X-ray diffractogram and differential scanning calorimetry analysis, respectively. 35959165 10 26 theme differential 1542:1553 arg1 calorimetry 1564:1574 differential scanning calorimetry 1542:1574 differential scanning calorimetry 1542:1574 Semi-crystalline nature and thermal stability were confirmed by X-ray diffractogram and differential scanning calorimetry analysis, respectively. 35959165 9 27 theme Protic 1296:1301 arg1 solvents 1315:1322 Protic and aprotic solvents 1296:1322 Protic and aprotic solvents for exchangeable protons 1296:1347 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 6 28 theme carbon 711:716 arg1 % 753:753 72.72-77.63% 742:753 72.72-77.63% 742:753 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 6 28 theme carbon 711:716 arg1 content 718:724 The carbon content 707:724 The carbon content 707:724 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 6 28 theme carbon 711:716 arg1 high 736:739 high 736:739 high 736:739 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 4 29 theme EPS 408:410 arg1 characterization 388:403 The chemical characterization 375:403 The chemical characterization of EPS 375:410 The chemical characterization of EPS was done using UV spectroscopy, Fourier transforms infrared spectroscopy, and gas chromatography-mass spectrometry. 35959165 8 30 dep compact 1034:1040 arg1 irregular 1043:1051 irregular 1043:1051 irregular 1043:1051 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 12 31 from use 1780:1782 arg1 industries 1812:1821 food, and pharmaceutical industries 1787:1821 food, and pharmaceutical industries 1787:1821 It can form a stable emulsion against different edible oil that makes it promising alternative for use in food, and pharmaceutical industries. 35959165 8 32 with filaments 990:998 arg1 lumps 1053:1057 compact, irregular lumps 1034:1057 compact, irregular lumps 1034:1057 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 8 32 with filaments 990:998 arg1 flakes 1071:1076 stacked flakes 1063:1076 stacked flakes of polysaccharides 1063:1095 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 8 32 with filaments 990:998 arg1 structure 1023:1031 three-dimensional structure 1005:1031 three-dimensional structure 1005:1031 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 0 33 theme possible 81:88 arg1 role 90:93 its possible role 77:93 its possible role as an emulsifier 77:110 Characterization of exopolysaccharide derived from Enterobacter ludwigii and its possible role as an emulsifier. 35959165 13 34 theme Supplementary 1824:1836 arg1 Information 1838:1848 Supplementary Information 1824:1848 Supplementary Information The online version 1824:1867 Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03279-z. 35959165 10 35 theme Semi-crystalline 1454:1469 arg1 nature 1471:1476 Semi-crystalline nature 1454:1476 Semi-crystalline nature 1454:1476 Semi-crystalline nature and thermal stability were confirmed by X-ray diffractogram and differential scanning calorimetry analysis, respectively. 35959165 9 36 theme aprotic 1307:1313 arg1 solvents 1315:1322 Protic and aprotic solvents 1296:1322 Protic and aprotic solvents for exchangeable protons 1296:1347 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 7 37 dep monosaccharides 845:859 arg1 galactose 879:887 galactose 879:887 galactose (4.25%) 879:895 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 37 dep monosaccharides 845:859 arg1 mannose 898:904 mannose 898:904 mannose (4.04%) 898:912 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 37 dep monosaccharides 845:859 arg1 glucose 861:867 glucose 861:867 glucose (16.91%) 861:876 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 37 dep monosaccharides 845:859 arg1 % 911:911 4.04% 907:911 4.04% 907:911 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 37 dep monosaccharides 845:859 arg1 % 875:875 16.91% 870:875 16.91% 870:875 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 37 dep monosaccharides 845:859 arg1 % 931:931 8.06% 927:931 8.06% 927:931 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 37 dep monosaccharides 845:859 arg1 % 894:894 4.25% 890:894 4.25% 890:894 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 37 dep monosaccharides 845:859 arg1 monosaccharides 845:859 different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) 835:932 different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) 835:932 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 37 dep monosaccharides 845:859 arg1 xylose 919:924 xylose 919:924 xylose (8.06%) 919:932 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 12 38 theme promising 1754:1762 arg1 alternative 1764:1774 promising alternative 1754:1774 it promising alternative 1751:1774 It can form a stable emulsion against different edible oil that makes it promising alternative for use in food, and pharmaceutical industries. 35959165 12 39 dep it 1751:1752 arg1 alternative 1764:1774 promising alternative 1754:1774 it promising alternative 1751:1774 It can form a stable emulsion against different edible oil that makes it promising alternative for use in food, and pharmaceutical industries. 35959165 7 40 theme EPS 961:963 arg1 presence 823:830 the presence 819:830 the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) 819:932 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 40 theme EPS 961:963 arg1 components 947:956 the major components 937:956 the major components of EPS 937:963 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 9 41 theme different 1130:1138 arg1 1D 1140:1141 different 1D 1130:1141 different 1D 1130:1141 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 0 42 theme exopolysaccharide 20:36 arg1 Characterization 0:15 Characterization 0:15 Characterization of exopolysaccharide 0:36 Characterization of exopolysaccharide derived from Enterobacter ludwigii and its possible role as an emulsifier. 35959165 12 43 theme food 1787:1790 arg1 industries 1812:1821 food, and pharmaceutical industries 1787:1821 food, and pharmaceutical industries 1787:1821 It can form a stable emulsion against different edible oil that makes it promising alternative for use in food, and pharmaceutical industries. 35959165 13 44 dep Information 1838:1848 arg1 version 1861:1867 The online version 1850:1867 Supplementary Information The online version 1824:1867 Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03279-z. 35959165 9 45 theme 1H-1H 1222:1226 arg1 NMR 1208:1210 1H NMR 1205:1210 1H NMR 1205:1210 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 45 theme 1H-1H 1222:1226 arg1 COSY 1228:1231 1H-1H COSY 1222:1231 1H-1H COSY 1222:1231 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 1 46 theme Enterobacter 113:124 arg1 ludwigii 126:133 Enterobacter ludwigii 113:133 Enterobacter ludwigii 113:133 Enterobacter ludwigii is an oral growing bacteria responsible for teeth blackening. 35959165 1 46 theme Enterobacter 113:124 arg1 oral 141:144 oral 141:144 oral 141:144 Enterobacter ludwigii is an oral growing bacteria responsible for teeth blackening. 35959165 5 47 theme Energy-dispersive 528:544 arg1 analysis 571:578 Energy-dispersive X-ray spectroscopy (EDS) analysis 528:578 Energy-dispersive X-ray spectroscopy (EDS) analysis of EPS 528:585 Energy-dispersive X-ray spectroscopy (EDS) analysis of EPS has revealed the presence of carbon > boron > nitrogen > phosphorous > calcium > sulfur > iron > potassium > magnesium. 35959165 9 48 theme 1H 1440:1441 arg1 spectrum 1443:1450 1H spectrum 1440:1450 1H spectrum 1440:1450 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 0 49 theme Enterobacter 51:62 arg1 ludwigii 64:71 Enterobacter ludwigii 51:71 Enterobacter ludwigii 51:71 Characterization of exopolysaccharide derived from Enterobacter ludwigii and its possible role as an emulsifier. 35959165 9 50 theme exchangeable 1328:1339 arg1 protons 1341:1347 exchangeable protons 1328:1347 exchangeable protons 1328:1347 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 3 51 theme biofilm 270:276 arg1 formation 278:286 biofilm formation 270:286 biofilm formation 270:286 The exopolysaccharide (EPS) cluster associated with biofilm formation was isolated using ethanol precipitation and the formaldehyde-sodium hydroxide method. 35959165 9 52 dep monomers 1384:1391 arg1 seven 1394:1398 seven 1394:1398 seven 1394:1398 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 52 dep monomers 1384:1391 arg1 one 1431:1433 one 1431:1433 one 1431:1433 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 52 dep monomers 1384:1391 arg1 monomers 1384:1391 eight distinguished monomers 1364:1391 eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum) 1364:1451 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 5 53 theme X-ray 546:550 arg1 EDS 566:568 EDS 566:568 EDS 566:568 Energy-dispersive X-ray spectroscopy (EDS) analysis of EPS has revealed the presence of carbon > boron > nitrogen > phosphorous > calcium > sulfur > iron > potassium > magnesium. 35959165 5 53 theme X-ray 546:550 arg1 spectroscopy 552:563 X-ray spectroscopy 546:563 Energy-dispersive X-ray spectroscopy (EDS) analysis of EPS 528:585 Energy-dispersive X-ray spectroscopy (EDS) analysis of EPS has revealed the presence of carbon > boron > nitrogen > phosphorous > calcium > sulfur > iron > potassium > magnesium. 35959165 9 54 theme Resonance 1164:1172 arg1 techniques 1193:1202 Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) 1147:1258 Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) 1147:1258 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 7 55 theme major 941:945 arg1 presence 823:830 the presence 819:830 the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) 819:932 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 7 55 theme major 941:945 arg1 components 947:956 the major components 937:956 the major components of EPS 937:963 The study showed the presence of different monosaccharides glucose (16.91%), galactose (4.25%), mannose (4.04%), and xylose (8.06%) as the major components of EPS. 35959165 4 56 theme chromatography-mass 494:512 arg1 spectrometry 514:525 gas chromatography-mass spectrometry 490:525 gas chromatography-mass spectrometry 490:525 The chemical characterization of EPS was done using UV spectroscopy, Fourier transforms infrared spectroscopy, and gas chromatography-mass spectrometry. 35959165 4 57 theme gas 490:492 arg1 spectrometry 514:525 gas chromatography-mass spectrometry 490:525 gas chromatography-mass spectrometry 490:525 The chemical characterization of EPS was done using UV spectroscopy, Fourier transforms infrared spectroscopy, and gas chromatography-mass spectrometry. 35959165 9 58 theme Nuclear 1147:1153 arg1 NMR 1175:1177 NMR 1175:1177 NMR 1175:1177 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 58 theme Nuclear 1147:1153 arg1 Resonance 1164:1172 Nuclear Magnetic Resonance 1147:1172 Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) 1147:1258 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 59 theme deuterated 1275:1284 arg1 solvents 1286:1293 different deuterated solvents 1265:1293 different deuterated solvents (Protic and aprotic solvents for exchangeable protons) 1265:1348 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 60 dep solvents 1286:1293 arg1 solvents 1315:1322 Protic and aprotic solvents 1296:1322 Protic and aprotic solvents for exchangeable protons 1296:1347 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 13 61 contain contains 1869:1876 arg2 material 1892:1899 supplementary material 1878:1899 supplementary material available at 10.1007/s13205-022-03279-z 1878:1939 Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03279-z. 35959165 13 61 contain contains 1869:1876 arg1 Information 1838:1848 Supplementary Information 1824:1848 Supplementary Information The online version 1824:1867 Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03279-z. 35959165 6 62 from EPS 763:765 arg1 % 753:753 72.72-77.63% 742:753 72.72-77.63% 742:753 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 6 62 from EPS 763:765 arg1 content 718:724 The carbon content 707:724 The carbon content 707:724 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 6 62 from EPS 763:765 arg1 high 736:739 high 736:739 high 736:739 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 9 63 theme Magnetic 1155:1162 arg1 NMR 1175:1177 NMR 1175:1177 NMR 1175:1177 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 63 theme Magnetic 1155:1162 arg1 Resonance 1164:1172 Nuclear Magnetic Resonance 1147:1172 Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) 1147:1258 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 6 64 from high 736:739 arg1 EPS 763:765 the EPS 759:765 the EPS due to polysaccharide composition 759:799 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 6 65 theme due 767:769 arg1 EPS 763:765 the EPS 759:765 the EPS due to polysaccharide composition 759:799 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 6 66 dep high 736:739 arg1 % 753:753 72.72-77.63% 742:753 72.72-77.63% 742:753 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 6 66 dep high 736:739 arg1 content 718:724 The carbon content 707:724 The carbon content 707:724 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 6 66 dep high 736:739 arg1 high 736:739 high 736:739 high 736:739 The carbon content was quite high (72.72-77.63%) in the EPS due to polysaccharide composition. 35959165 5 67 theme carbon > boron > nitrogen > phosphorous > calcium > sulfur > iron > potassium > magnesium 616:704 arg1 presence 604:611 the presence 600:611 the presence of carbon > boron > nitrogen > phosphorous > calcium > sulfur > iron > potassium > magnesium 600:704 Energy-dispersive X-ray spectroscopy (EDS) analysis of EPS has revealed the presence of carbon > boron > nitrogen > phosphorous > calcium > sulfur > iron > potassium > magnesium. 35959165 4 68 theme chemical 379:386 arg1 characterization 388:403 The chemical characterization 375:403 The chemical characterization of EPS 375:410 The chemical characterization of EPS was done using UV spectroscopy, Fourier transforms infrared spectroscopy, and gas chromatography-mass spectrometry. 35959165 8 69 theme thin 985:988 arg1 filaments 990:998 thin filaments 985:998 thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides 985:1095 It appears such as thin filaments with three-dimensional structure, compact, irregular lumps and stacked flakes of polysaccharides. 35959165 3 70 theme ethanol 307:313 arg1 precipitation 315:327 ethanol precipitation 307:327 ethanol precipitation 307:327 The exopolysaccharide (EPS) cluster associated with biofilm formation was isolated using ethanol precipitation and the formaldehyde-sodium hydroxide method. 35959165 9 71 theme 1H-13C 1247:1252 arg1 NMR 1208:1210 1H NMR 1205:1210 1H NMR 1205:1210 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 71 theme 1H-13C 1247:1252 arg1 HMBC 1254:1257 1H-13C HMBC 1247:1257 1H-13C HMBC 1247:1257 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 13 72 theme online 1854:1859 arg1 version 1861:1867 The online version 1850:1867 Supplementary Information The online version 1824:1867 Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03279-z. 35959165 9 73 dep techniques 1193:1202 arg1 NMR 1208:1210 1H NMR 1205:1210 1H NMR 1205:1210 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 73 dep techniques 1193:1202 arg1 NMR 1217:1219 13C NMR 1213:1219 13C NMR 1213:1219 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 73 dep techniques 1193:1202 arg1 COSY 1228:1231 1H-1H COSY 1222:1231 1H-1H COSY 1222:1231 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 73 dep techniques 1193:1202 arg1 HSQC 1241:1244 1H-13C HSQC 1234:1244 1H-13C HSQC 1234:1244 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 73 dep techniques 1193:1202 arg1 HMBC 1254:1257 1H-13C HMBC 1247:1257 1H-13C HMBC 1247:1257 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 13 74 theme available 1901:1909 arg1 material 1892:1899 supplementary material 1878:1899 supplementary material available at 10.1007/s13205-022-03279-z 1878:1939 Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03279-z. 35959165 3 75 theme hydroxide 357:365 arg1 method 367:372 the formaldehyde-sodium hydroxide method 333:372 the formaldehyde-sodium hydroxide method 333:372 The exopolysaccharide (EPS) cluster associated with biofilm formation was isolated using ethanol precipitation and the formaldehyde-sodium hydroxide method. 35959165 4 76 theme infrared 463:470 arg1 spectroscopy 472:483 infrared spectroscopy 463:483 infrared spectroscopy 463:483 The chemical characterization of EPS was done using UV spectroscopy, Fourier transforms infrared spectroscopy, and gas chromatography-mass spectrometry. 35959165 11 77 theme antioxidant 1622:1632 arg1 potential 1634:1642 antioxidant potential 1622:1642 antioxidant potential 1622:1642 The EPS further shows antioxidant potential in a concentration-dependent manner. 35959165 12 78 theme edible 1729:1734 arg1 oil 1736:1738 different edible oil 1719:1738 different edible oil 1719:1738 It can form a stable emulsion against different edible oil that makes it promising alternative for use in food, and pharmaceutical industries. 35959165 9 79 theme distinguished 1370:1382 arg1 seven 1394:1398 seven 1394:1398 seven 1394:1398 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 79 theme distinguished 1370:1382 arg1 one 1431:1433 one 1431:1433 one 1431:1433 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 9 79 theme distinguished 1370:1382 arg1 monomers 1384:1391 eight distinguished monomers 1364:1391 eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum) 1364:1451 The EPS was also examined using different 1D, 2D Nuclear Magnetic Resonance (NMR) spectroscopy techniques (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC) with different deuterated solvents (Protic and aprotic solvents for exchangeable protons), which showed eight distinguished monomers (seven confirmed by HSQC spectrum and one from 1H spectrum). 35959165 10 80 theme diffractogram 1524:1536 arg1 analysis 1576:1583 X-ray diffractogram and differential scanning calorimetry analysis 1518:1583 X-ray diffractogram and differential scanning calorimetry analysis 1518:1583 Semi-crystalline nature and thermal stability were confirmed by X-ray diffractogram and differential scanning calorimetry analysis, respectively. 35959165 5 81 theme EPS 583:585 arg1 analysis 571:578 Energy-dispersive X-ray spectroscopy (EDS) analysis 528:578 Energy-dispersive X-ray spectroscopy (EDS) analysis of EPS 528:585 Energy-dispersive X-ray spectroscopy (EDS) analysis of EPS has revealed the presence of carbon > boron > nitrogen > phosphorous > calcium > sulfur > iron > potassium > magnesium. 35959165 12 82 theme stable 1695:1700 arg1 emulsion 1702:1709 a stable emulsion 1693:1709 a stable emulsion against different edible oil that makes it promising alternative for use in food, and pharmaceutical industries 1693:1821 It can form a stable emulsion against different edible oil that makes it promising alternative for use in food, and pharmaceutical industries. 35959165 4 83 dep Fourier 444:450 arg1 transforms 452:461 transforms 452:461 transforms infrared spectroscopy 452:483 The chemical characterization of EPS was done using UV spectroscopy, Fourier transforms infrared spectroscopy, and gas chromatography-mass spectrometry. 35312473 8 0 theme fatty 926:930 arg1 acids 932:936 The major cellular fatty acids 907:936 The major cellular fatty acids 907:936 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 2 1 theme anaerobic 122:130 arg1 strain 142:147 An anaerobic bacterial strain 119:147 An anaerobic bacterial strain 119:147 An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. 35312473 6 2 theme alcoholic 797:805 arg1 compounds 807:815 alcoholic compounds 797:815 alcoholic compounds 797:815 The strain was also able to use amino acids and some organic acids and alcoholic compounds for growth. 35312473 4 3 dep 0.7 470:472 arg1 to 467:468 to 467:468 to 467:468 Growth occurred at 20-45 °C, initial pH 5.5-8.5 and with up to 0.7 M NH4Cl, with optimum growth at 37-42 °C and pH 8.0. 35312473 13 4 theme chemotaxonomic 1774:1787 arg1 data 1820:1823 genomic, chemotaxonomic, biochemical and physiological data 1765:1823 genomic, chemotaxonomic, biochemical and physiological data 1765:1823 Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. 35312473 10 5 theme G+C 1270:1272 arg1 content 1274:1280 The genomic DNA G+C content 1254:1280 The genomic DNA G+C content 1254:1280 The genomic DNA G+C content was 29.0 mol%. 35312473 10 5 theme G+C 1270:1272 arg1 % 1294:1294 29.0 mol% 1286:1294 29.0 mol% 1286:1294 The genomic DNA G+C content was 29.0 mol%. 35312473 2 6 theme molecular 292:300 arg1 methods 312:318 phenotypic and molecular taxonomic methods 277:318 phenotypic and molecular taxonomic methods 277:318 An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. 35312473 15 7 theme =DSM 1981:1984 arg1 T 2004:2004 =DSM 110247T=JCM 39107 T 1981:2004 =DSM 110247T=JCM 39107 T 1981:2004 The type strain is AMB_01T (=DSM 110247T=JCM 39107 T). 35312473 15 7 theme =DSM 1981:1984 arg1 AMB_01T 1972:1978 AMB_01T 1972:1978 AMB_01T (=DSM 110247T=JCM 39107 T) 1972:2005 The type strain is AMB_01T (=DSM 110247T=JCM 39107 T). 35312473 12 8 theme acid 1564:1567 arg1 sequences 1569:1577 genome nucleotide and amino acid sequences 1536:1577 sequences 1569:1577 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 10 9 theme genomic 1258:1264 arg1 content 1274:1280 The genomic DNA G+C content 1254:1280 The genomic DNA G+C content 1254:1280 The genomic DNA G+C content was 29.0 mol%. 35312473 10 9 theme genomic 1258:1264 arg1 % 1294:1294 29.0 mol% 1286:1294 29.0 mol% 1286:1294 The genomic DNA G+C content was 29.0 mol%. 35312473 9 10 theme gene 1106:1109 arg1 similarity 1120:1129 The highest 16S rRNA gene sequence similarity 1085:1129 The highest 16S rRNA gene sequence similarity 1085:1129 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 12 11 theme digital 1437:1443 arg1 hybridisation 1453:1465 highest digital DNA-DNA hybridisation 1429:1465 highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) 1429:1671 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 13 12 theme genomic 1765:1771 arg1 data 1820:1823 genomic, chemotaxonomic, biochemical and physiological data 1765:1823 genomic, chemotaxonomic, biochemical and physiological data 1765:1823 Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. 35312473 12 13 with identity 1522:1529 arg1 nucleotide 1543:1552 genome nucleotide and amino acid sequences 1536:1577 nucleotide 1543:1552 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 13 with identity 1522:1529 arg1 sequences 1569:1577 genome nucleotide and amino acid sequences 1536:1577 sequences 1569:1577 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 9 14 theme 16S 1097:1099 arg1 similarity 1120:1129 The highest 16S rRNA gene sequence similarity 1085:1129 The highest 16S rRNA gene sequence similarity 1085:1129 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 5 15 theme high 544:547 arg1 density 554:560 high cell density 544:560 high cell density 544:560 AMB_01T achieved high cell density and highest acetate production when grown on carbohydrates, including monomers, disaccharides and polysaccharides, such as glucose, maltose, cellobiose and starch. 35312473 12 16 theme close 1406:1410 arg1 relatives 1412:1420 close relatives 1406:1420 close relatives 1406:1420 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 3 17 theme AMB_01T 330:336 arg1 Cells 321:325 Cells 321:325 Cells of AMB_01T 321:336 Cells of AMB_01T are coccus-shaped and often occur arranged as diplococci or sarcina. 35312473 13 18 theme name 1897:1900 arg1 sp 1931:1932 the name Miniphocaeibacter halophilus sp 1893:1932 the name Miniphocaeibacter halophilus sp 1893:1932 Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. 35312473 2 19 theme biogas 236:241 arg1 digester 243:250 a high-ammonia biogas digester 221:250 a high-ammonia biogas digester 221:250 An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. 35312473 11 20 theme genes 1323:1327 arg1 genes 1323:1327 genes 1323:1327 genes 1323:1327 An almost complete set of genes for the acetyl-CoA pathway was found. 35312473 11 20 theme genes 1323:1327 arg1 set 1316:1318 An almost complete set 1297:1318 An almost complete set of genes for the acetyl-CoA pathway 1297:1354 An almost complete set of genes for the acetyl-CoA pathway was found. 35312473 13 21 theme halophilus 1920:1929 arg1 sp 1931:1932 the name Miniphocaeibacter halophilus sp 1893:1932 the name Miniphocaeibacter halophilus sp 1893:1932 Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. 35312473 2 22 theme phenotypic 277:286 arg1 methods 312:318 phenotypic and molecular taxonomic methods 277:318 phenotypic and molecular taxonomic methods 277:318 An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. 35312473 12 23 theme amino 1558:1562 arg1 sequences 1569:1577 genome nucleotide and amino acid sequences 1536:1577 sequences 1569:1577 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 24 theme nucleotide 1511:1520 arg1 identity 1522:1529 highest average nucleotide identity 1495:1529 highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) 1495:1624 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 24 theme nucleotide 1511:1520 arg1 magna 1481:1485 Finegoldia magna 1470:1485 Finegoldia magna (23 %) 1470:1492 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 10 25 theme mol 1291:1293 arg1 content 1274:1280 The genomic DNA G+C content 1254:1280 The genomic DNA G+C content 1254:1280 The genomic DNA G+C content was 29.0 mol%. 35312473 10 25 theme mol 1291:1293 arg1 % 1294:1294 29.0 mol% 1286:1294 29.0 mol% 1286:1294 The genomic DNA G+C content was 29.0 mol%. 35312473 9 26 theme Miniphocaeibacter 1146:1162 arg1 massiliensis 1164:1175 Miniphocaeibacter massiliensis 1146:1175 Miniphocaeibacter massiliensis (96.6 %) 1146:1184 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 9 26 theme Miniphocaeibacter 1146:1162 arg1 % 1183:1183 96.6 % 1178:1183 96.6 % 1178:1183 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 4 27 theme 37-42 °C and 506:517 arg1 pH 519:520 37-42 °C and pH 8.0 506:524 37-42 °C and pH 8.0 506:524 Growth occurred at 20-45 °C, initial pH 5.5-8.5 and with up to 0.7 M NH4Cl, with optimum growth at 37-42 °C and pH 8.0. 35312473 12 28 dep massiliensis 1585:1596 arg1 % 1609:1609 72 and 73 % 1599:1609 72 and 73 % 1599:1609 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 13 29 theme novel 1868:1872 arg1 species 1874:1880 a novel species 1866:1880 a novel species 1866:1880 Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. 35312473 5 30 theme highest 566:572 arg1 production 582:591 highest acetate production 566:591 highest acetate production 566:591 AMB_01T achieved high cell density and highest acetate production when grown on carbohydrates, including monomers, disaccharides and polysaccharides, such as glucose, maltose, cellobiose and starch. 35312473 12 31 theme highest 1495:1501 arg1 identity 1522:1529 highest average nucleotide identity 1495:1529 highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) 1495:1624 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 31 theme highest 1495:1501 arg1 magna 1481:1485 Finegoldia magna 1470:1485 Finegoldia magna (23 %) 1470:1492 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 4 32 dep NH4Cl 476:480 arg1 M 474:474 M 474:474 M 474:474 Growth occurred at 20-45 °C, initial pH 5.5-8.5 and with up to 0.7 M NH4Cl, with optimum growth at 37-42 °C and pH 8.0. 35312473 0 33 theme Miniphocaeibacter 0:16 arg1 sp 29:30 Miniphocaeibacter halophilus sp 0:30 Miniphocaeibacter halophilus sp. 0:31 Miniphocaeibacter halophilus sp. 35312473 1 34 theme biogas 104:109 arg1 system 111:116 a biogas system 102:116 a biogas system 102:116 nov., an ammonium-tolerant acetate-producing bacterium isolated from a biogas system. 35312473 8 35 dep feature 950:956 arg1 iso-C17  961:968 iso-C17  961:968 iso-C17 : 1I and/or anteiso-C17 : 1B 961:996 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 2 36 theme mesophilic 185:194 arg1 enrichment 207:216 mesophilic propionate enrichment 185:216 mesophilic propionate enrichment of a high-ammonia biogas digester 185:250 An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. 35312473 9 37 theme phylum 1223:1228 arg1 Firmicutes 1241:1250 Firmicutes 1241:1250 Firmicutes 1241:1250 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 9 37 theme phylum 1223:1228 arg1 Peptoniphilaceae 1205:1220 the family Peptoniphilaceae 1194:1220 the family Peptoniphilaceae 1194:1220 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 9 37 theme phylum 1223:1228 arg1 Bacillota 1230:1238 phylum Bacillota 1223:1238 phylum Bacillota (Firmicutes) 1223:1251 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 12 38 theme nucleotide 1646:1655 arg1 identity 1657:1664 highest average nucleotide identity 1630:1664 highest average nucleotide identity (87 %) 1630:1671 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 38 theme nucleotide 1646:1655 arg1 % 1670:1670 87 % 1667:1670 87 % 1667:1670 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 38 theme nucleotide 1646:1655 arg1 magna 1481:1485 Finegoldia magna 1470:1485 Finegoldia magna (23 %) 1470:1492 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 39 theme average 1638:1644 arg1 identity 1657:1664 highest average nucleotide identity 1630:1664 highest average nucleotide identity (87 %) 1630:1671 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 39 theme average 1638:1644 arg1 % 1670:1670 87 % 1667:1670 87 % 1667:1670 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 39 theme average 1638:1644 arg1 magna 1481:1485 Finegoldia magna 1470:1485 Finegoldia magna (23 %) 1470:1492 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 8 40 theme cellular 917:924 arg1 acids 932:936 The major cellular fatty acids 907:936 The major cellular fatty acids 907:936 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 1 41 theme ammonium-tolerant 42:58 arg1 bacterium 78:86 an ammonium-tolerant acetate-producing bacterium 39:86 an ammonium-tolerant acetate-producing bacterium 39:86 nov., an ammonium-tolerant acetate-producing bacterium isolated from a biogas system. 35312473 1 41 theme ammonium-tolerant 42:58 arg1 nov. 33:36 nov. 33:36 nov. 33:36 nov., an ammonium-tolerant acetate-producing bacterium isolated from a biogas system. 35312473 2 42 theme bacterial 132:140 arg1 strain 142:147 An anaerobic bacterial strain 119:147 An anaerobic bacterial strain 119:147 An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. 35312473 4 43 from pH 519:520 arg1 growth 496:501 optimum growth 488:501 optimum growth at 37-42 °C and pH 8.0 488:524 Growth occurred at 20-45 °C, initial pH 5.5-8.5 and with up to 0.7 M NH4Cl, with optimum growth at 37-42 °C and pH 8.0. 35312473 13 44 theme data 1820:1823 arg1 Analysis 1753:1760 Analysis 1753:1760 Analysis of genomic, chemotaxonomic, biochemical and physiological data 1753:1823 Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. 35312473 4 45 dep M 474:474 arg1 0.7 470:472 0.7 470:472 0.7 470:472 Growth occurred at 20-45 °C, initial pH 5.5-8.5 and with up to 0.7 M NH4Cl, with optimum growth at 37-42 °C and pH 8.0. 35312473 8 46 theme summed 1032:1037 arg1 feature 1039:1045 summed feature 3 1032:1047 summed feature 3 1032:1047 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 4 47 theme 20-45 °C 426:433 arg1 pH 444:445 20-45 °C, initial pH 5.5-8.5 426:453 20-45 °C, initial pH 5.5-8.5 426:453 Growth occurred at 20-45 °C, initial pH 5.5-8.5 and with up to 0.7 M NH4Cl, with optimum growth at 37-42 °C and pH 8.0. 35312473 9 48 dep found 1131:1135 arg1 massiliensis 1164:1175 Miniphocaeibacter massiliensis 1146:1175 Miniphocaeibacter massiliensis (96.6 %) 1146:1184 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 9 48 dep found 1131:1135 arg1 % 1183:1183 96.6 % 1178:1183 96.6 % 1178:1183 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 7 49 theme main 855:858 arg1 product 860:866 the main product 851:866 the main product 851:866 Acetate was formed as the main product and yeast was not required for growth. 35312473 7 49 theme main 855:858 arg1 Acetate 829:835 Acetate 829:835 Acetate 829:835 Acetate was formed as the main product and yeast was not required for growth. 35312473 12 50 with identity 1657:1664 arg1 nucleotide 1543:1552 genome nucleotide and amino acid sequences 1536:1577 nucleotide 1543:1552 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 50 with identity 1657:1664 arg1 sequences 1569:1577 genome nucleotide and amino acid sequences 1536:1577 sequences 1569:1577 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 6 51 theme organic 779:785 arg1 acids 787:791 some organic acids 774:791 some organic acids 774:791 The strain was also able to use amino acids and some organic acids and alcoholic compounds for growth. 35312473 2 52 theme taxonomic 302:310 arg1 methods 312:318 phenotypic and molecular taxonomic methods 277:318 phenotypic and molecular taxonomic methods 277:318 An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. 35312473 10 53 theme DNA 1266:1268 arg1 content 1274:1280 The genomic DNA G+C content 1254:1280 The genomic DNA G+C content 1254:1280 The genomic DNA G+C content was 29.0 mol%. 35312473 10 53 theme DNA 1266:1268 arg1 % 1294:1294 29.0 mol% 1286:1294 29.0 mol% 1286:1294 The genomic DNA G+C content was 29.0 mol%. 35312473 12 54 theme DNA-DNA 1445:1451 arg1 hybridisation 1453:1465 highest digital DNA-DNA hybridisation 1429:1465 highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) 1429:1671 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 6 55 theme amino 758:762 arg1 acids 764:768 amino acids 758:768 amino acids 758:768 The strain was also able to use amino acids and some organic acids and alcoholic compounds for growth. 35312473 15 56 theme type 1957:1960 arg1 AMB_01T 1972:1978 AMB_01T 1972:1978 AMB_01T (=DSM 110247T=JCM 39107 T) 1972:2005 The type strain is AMB_01T (=DSM 110247T=JCM 39107 T). 35312473 15 56 theme type 1957:1960 arg1 strain 1962:1967 The type strain 1953:1967 The type strain 1953:1967 The type strain is AMB_01T (=DSM 110247T=JCM 39107 T). 35312473 9 57 theme highest 1089:1095 arg1 similarity 1120:1129 The highest 16S rRNA gene sequence similarity 1085:1129 The highest 16S rRNA gene sequence similarity 1085:1129 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 9 58 theme rRNA 1101:1104 arg1 similarity 1120:1129 The highest 16S rRNA gene sequence similarity 1085:1129 The highest 16S rRNA gene sequence similarity 1085:1129 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 2 59 theme digester 243:250 arg1 enrichment 207:216 mesophilic propionate enrichment 185:216 mesophilic propionate enrichment of a high-ammonia biogas digester 185:250 An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. 35312473 5 60 theme cell 549:552 arg1 density 554:560 high cell density 544:560 high cell density 544:560 AMB_01T achieved high cell density and highest acetate production when grown on carbohydrates, including monomers, disaccharides and polysaccharides, such as glucose, maltose, cellobiose and starch. 35312473 12 61 theme highest 1429:1435 arg1 hybridisation 1453:1465 highest digital DNA-DNA hybridisation 1429:1465 highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) 1429:1671 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 13 62 theme Miniphocaeibacter 1902:1918 arg1 sp 1931:1932 the name Miniphocaeibacter halophilus sp 1893:1932 the name Miniphocaeibacter halophilus sp 1893:1932 Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. 35312473 12 63 theme genome 1536:1541 arg1 nucleotide 1543:1552 genome nucleotide and amino acid sequences 1536:1577 nucleotide 1543:1552 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 11 64 theme complete 1307:1314 arg1 genes 1323:1327 genes 1323:1327 genes 1323:1327 An almost complete set of genes for the acetyl-CoA pathway was found. 35312473 11 64 theme complete 1307:1314 arg1 set 1316:1318 An almost complete set 1297:1318 An almost complete set of genes for the acetyl-CoA pathway 1297:1354 An almost complete set of genes for the acetyl-CoA pathway was found. 35312473 11 65 theme acetyl-CoA 1337:1346 arg1 pathway 1348:1354 the acetyl-CoA pathway 1333:1354 the acetyl-CoA pathway 1333:1354 An almost complete set of genes for the acetyl-CoA pathway was found. 35312473 15 66 theme 110247T=JCM 1986:1996 arg1 T 2004:2004 =DSM 110247T=JCM 39107 T 1981:2004 =DSM 110247T=JCM 39107 T 1981:2004 The type strain is AMB_01T (=DSM 110247T=JCM 39107 T). 35312473 15 66 theme 110247T=JCM 1986:1996 arg1 AMB_01T 1972:1978 AMB_01T 1972:1978 AMB_01T (=DSM 110247T=JCM 39107 T) 1972:2005 The type strain is AMB_01T (=DSM 110247T=JCM 39107 T). 35312473 12 67 theme average 1503:1509 arg1 identity 1522:1529 highest average nucleotide identity 1495:1529 highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) 1495:1624 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 67 theme average 1503:1509 arg1 magna 1481:1485 Finegoldia magna 1470:1485 Finegoldia magna (23 %) 1470:1492 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 8 68 dep C16  1050:1053 arg1 iso-C15  1067:1074 iso-C15  1067:1074 iso-C15  1067:1074 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 8 68 dep C16  1050:1053 arg1 2OH 1079:1081 2OH 1079:1081 2OH 1079:1081 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 8 68 dep C16  1050:1053 arg1  1ω7 1055:1058  1ω7 1055:1058  1ω7 1055:1058 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 4 69 dep 20-45 °C 426:433 arg1 initial 436:442 initial 436:442 initial 436:442 Growth occurred at 20-45 °C, initial pH 5.5-8.5 and with up to 0.7 M NH4Cl, with optimum growth at 37-42 °C and pH 8.0. 35312473 12 70 theme novel 1738:1742 arg1 species 1744:1750 a novel species 1736:1750 a novel species 1736:1750 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 1 71 theme acetate-producing 60:76 arg1 bacterium 78:86 an ammonium-tolerant acetate-producing bacterium 39:86 an ammonium-tolerant acetate-producing bacterium 39:86 nov., an ammonium-tolerant acetate-producing bacterium isolated from a biogas system. 35312473 1 71 theme acetate-producing 60:76 arg1 nov. 33:36 nov. 33:36 nov. 33:36 nov., an ammonium-tolerant acetate-producing bacterium isolated from a biogas system. 35312473 12 72 theme Genome 1367:1372 arg1 comparisons 1374:1384 Genome comparisons 1367:1384 Genome comparisons between AMB_01T and close relatives 1367:1420 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 4 73 theme optimum 488:494 arg1 growth 496:501 optimum growth 488:501 optimum growth at 37-42 °C and pH 8.0 488:524 Growth occurred at 20-45 °C, initial pH 5.5-8.5 and with up to 0.7 M NH4Cl, with optimum growth at 37-42 °C and pH 8.0. 35312473 8 74 dep iso-C17  961:968 arg1  1B 994:996  1B 994:996 iso-C17 : 1I and/or anteiso-C17 : 1B 961:996 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 8 74 dep iso-C17  961:968 arg1 anteiso-C17  981:992 anteiso-C17  981:992 anteiso-C17  981:992 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 8 74 dep iso-C17  961:968 arg1  1I 970:972  1I 970:972  1I 970:972 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 0 75 theme halophilus 18:27 arg1 sp 29:30 Miniphocaeibacter halophilus sp 0:30 Miniphocaeibacter halophilus sp. 0:31 Miniphocaeibacter halophilus sp. 35312473 5 76 theme acetate 574:580 arg1 production 582:591 highest acetate production 566:591 highest acetate production 566:591 AMB_01T achieved high cell density and highest acetate production when grown on carbohydrates, including monomers, disaccharides and polysaccharides, such as glucose, maltose, cellobiose and starch. 35312473 12 77 theme Finegoldia 1470:1479 arg1 identity 1522:1529 highest average nucleotide identity 1495:1529 highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) 1495:1624 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 77 theme Finegoldia 1470:1479 arg1 magna 1481:1485 Finegoldia magna 1470:1485 Finegoldia magna (23 %) 1470:1492 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 77 theme Finegoldia 1470:1479 arg1 % 1491:1491 23 % 1488:1491 23 % 1488:1491 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 77 theme Finegoldia 1470:1479 arg1 identity 1657:1664 highest average nucleotide identity 1630:1664 highest average nucleotide identity (87 %) 1630:1671 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 2 78 theme propionate 196:205 arg1 enrichment 207:216 mesophilic propionate enrichment 185:216 mesophilic propionate enrichment of a high-ammonia biogas digester 185:250 An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. 35312473 8 79 dep summed 943:948 arg1 C16  1050:1053 C16  1050:1053 C16  1050:1053 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 9 80 theme family 1198:1203 arg1 Peptoniphilaceae 1205:1220 the family Peptoniphilaceae 1194:1220 the family Peptoniphilaceae 1194:1220 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 9 80 theme family 1198:1203 arg1 Bacillota 1230:1238 phylum Bacillota 1223:1238 phylum Bacillota (Firmicutes) 1223:1251 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 12 81 theme Schnuerera 1678:1687 arg1 ultunensis 1689:1698 Schnuerera ultunensis 1678:1698 Schnuerera ultunensis 1678:1698 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 3 82 dep occur 366:370 arg1 arranged 372:379 arranged 372:379 occur arranged as diplococci or sarcina 366:404 Cells of AMB_01T are coccus-shaped and often occur arranged as diplococci or sarcina. 35312473 2 83 theme high-ammonia 223:234 arg1 digester 243:250 a high-ammonia biogas digester 221:250 a high-ammonia biogas digester 221:250 An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. 35312473 13 84 theme strain 1840:1845 arg1 AMB_01T 1847:1853 strain AMB_01T 1840:1853 strain AMB_01T 1840:1853 Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. 35312473 12 85 theme highest 1630:1636 arg1 identity 1657:1664 highest average nucleotide identity 1630:1664 highest average nucleotide identity (87 %) 1630:1671 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 85 theme highest 1630:1636 arg1 % 1670:1670 87 % 1667:1670 87 % 1667:1670 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 12 85 theme highest 1630:1636 arg1 magna 1481:1485 Finegoldia magna 1470:1485 Finegoldia magna (23 %) 1470:1492 Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. 35312473 13 86 theme biochemical 1790:1800 arg1 data 1820:1823 genomic, chemotaxonomic, biochemical and physiological data 1765:1823 genomic, chemotaxonomic, biochemical and physiological data 1765:1823 Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. 35312473 8 87 theme major 911:915 arg1 acids 932:936 The major cellular fatty acids 907:936 The major cellular fatty acids 907:936 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 9 88 theme sequence 1111:1118 arg1 similarity 1120:1129 The highest 16S rRNA gene sequence similarity 1085:1129 The highest 16S rRNA gene sequence similarity 1085:1129 The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). 35312473 8 89 dep C18  1000:1003 arg1 C14  1011:1014 C14  1011:1014 C14  1011:1014 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 8 89 dep C18  1000:1003 arg1  0 1025:1026  0 1025:1026  0 1025:1026 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 8 89 dep C18  1000:1003 arg1 C16  1020:1023 C16  1020:1023 C16  1020:1023 The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). 35312473 13 90 theme physiological 1806:1818 arg1 data 1820:1823 genomic, chemotaxonomic, biochemical and physiological data 1765:1823 genomic, chemotaxonomic, biochemical and physiological data 1765:1823 Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. 35231142 10 0 theme aboveground 1649:1659 arg1 responses 1661:1669 aboveground responses 1649:1669 aboveground responses 1649:1669 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 5 1 theme forb 693:696 arg1 species 698:704 forb species 693:704 forb species 693:704 Compared with forb species, grass and sedge species exhibited distinct rhizosheaths; moreover, grasses and sedges expanded their rhizosheaths with increasing N-addition rate which allowed them to colonize belowground habitats. 35231142 8 2 theme N 1345:1345 arg1 enrichment 1347:1356 N enrichment 1345:1356 N enrichment 1345:1356 This enhanced the tolerance of grasses and sedges to stresses induced by N enrichment. 35231142 4 3 from changes 615:621 arg1 composition 642:652 plant community composition 626:652 plant community composition 626:652 We found that rhizosheath formation differed among plant functional groups and contributed to changes in plant community composition induced by N enrichment. 35231142 6 4 theme rhizosphere 1080:1090 arg1 soil 1092:1095 their rhizosphere soil 1074:1095 their rhizosphere soil 1074:1095 Grasses also shaped a different microenvironment around their roots compared with forbs by affecting the physicochemical, biological, and stress-avoiding properties of their rhizosphere soil. 35231142 10 5 theme exclusion 1785:1793 arg1 contribution 1757:1768 the contribution 1753:1768 the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition 1753:1868 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 7 6 theme carboxylic 1187:1196 arg1 anions 1198:1203 carboxylic anions 1187:1203 carboxylic anions 1187:1203 Rhizosheaths act as a "biofilm-like shield" by the accumulation of protective compounds, carboxylic anions and polysaccharides, determined by both plants and microorganisms. 35231142 8 7 theme grasses 1303:1309 arg1 tolerance 1290:1298 the tolerance 1286:1298 the tolerance of grasses and sedges to stresses induced by N enrichment 1286:1356 This enhanced the tolerance of grasses and sedges to stresses induced by N enrichment. 35231142 1 8 theme atmospheric 173:183 arg1 N 195:195 N 195:195 N 195:195 Belowground plant traits play important roles in plant diversity loss driven by atmospheric nitrogen (N) deposition. 35231142 1 8 theme atmospheric 173:183 arg1 nitrogen 185:192 atmospheric nitrogen 173:192 atmospheric nitrogen (N) deposition 173:207 Belowground plant traits play important roles in plant diversity loss driven by atmospheric nitrogen (N) deposition. 35231142 7 9 theme anions 1198:1203 arg1 accumulation 1149:1160 the accumulation 1145:1160 the accumulation of protective compounds, carboxylic anions and polysaccharides 1145:1223 Rhizosheaths act as a "biofilm-like shield" by the accumulation of protective compounds, carboxylic anions and polysaccharides, determined by both plants and microorganisms. 35231142 10 10 theme enrichment 1693:1702 arg1 conditions 1677:1686 conditions 1677:1686 conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition 1677:1868 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 4 11 theme rhizosheath 535:545 arg1 formation 547:555 rhizosheath formation 535:555 rhizosheath formation 535:555 We found that rhizosheath formation differed among plant functional groups and contributed to changes in plant community composition induced by N enrichment. 35231142 9 12 theme N-enriched 1532:1541 arg1 conditions 1543:1552 N-enriched conditions 1532:1552 N-enriched conditions 1532:1552 Conversely, forbs lacked the protective rhizosheaths which renders their roots sensitive to stresses induced by N enrichment, thus contributing to their disappearance under N-enriched conditions. 35231142 10 13 theme mechanistic 1724:1734 arg1 understanding 1736:1748 our mechanistic understanding 1720:1748 our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition 1720:1868 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 4 14 theme community 632:640 arg1 composition 642:652 plant community composition 626:652 plant community composition 626:652 We found that rhizosheath formation differed among plant functional groups and contributed to changes in plant community composition induced by N enrichment. 35231142 10 15 theme N 1691:1691 arg1 enrichment 1693:1702 N enrichment 1691:1702 N enrichment 1691:1702 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 5 16 theme grass 707:711 arg1 species 723:729 grass and sedge species 707:729 species 723:729 Compared with forb species, grass and sedge species exhibited distinct rhizosheaths; moreover, grasses and sedges expanded their rhizosheaths with increasing N-addition rate which allowed them to colonize belowground habitats. 35231142 10 17 theme N 1857:1857 arg1 deposition 1859:1868 N deposition 1857:1868 N deposition 1857:1868 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 4 18 theme plant 626:630 arg1 composition 642:652 plant community composition 626:652 plant community composition 626:652 We found that rhizosheath formation differed among plant functional groups and contributed to changes in plant community composition induced by N enrichment. 35231142 9 19 theme protective 1388:1397 arg1 rhizosheaths 1399:1410 the protective rhizosheaths 1384:1410 the protective rhizosheaths which renders their roots sensitive to stresses induced by N enrichment, thus contributing to their disappearance under N-enriched conditions 1384:1552 Conversely, forbs lacked the protective rhizosheaths which renders their roots sensitive to stresses induced by N enrichment, thus contributing to their disappearance under N-enriched conditions. 35231142 7 20 theme protective 1165:1174 arg1 compounds 1176:1184 protective compounds 1165:1184 protective compounds 1165:1184 Rhizosheaths act as a "biofilm-like shield" by the accumulation of protective compounds, carboxylic anions and polysaccharides, determined by both plants and microorganisms. 35231142 2 21 theme belowground 281:291 arg1 traits 293:298 patterning belowground traits 270:298 patterning belowground traits 270:298 However, the way N enrichment shapes plant microhabitats by patterning belowground traits and finally determines aboveground responses is poorly understood. 35231142 10 22 theme competitive 1773:1783 arg1 exclusion 1785:1793 competitive exclusion 1773:1793 competitive exclusion 1773:1793 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 1 23 theme nitrogen 185:192 arg1 deposition 198:207 atmospheric nitrogen (N) deposition 173:207 atmospheric nitrogen (N) deposition 173:207 Belowground plant traits play important roles in plant diversity loss driven by atmospheric nitrogen (N) deposition. 35231142 3 24 theme plant 417:421 arg1 species 423:429 74 plant species 414:429 74 plant species 414:429 Here, we investigated the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China. 35231142 3 25 from trait 405:409 arg1 experiments 462:472 seven N-addition simulation experiments 434:472 seven N-addition simulation experiments 434:472 Here, we investigated the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China. 35231142 7 26 theme compounds 1176:1184 arg1 accumulation 1149:1160 the accumulation 1145:1160 the accumulation of protective compounds, carboxylic anions and polysaccharides 1145:1223 Rhizosheaths act as a "biofilm-like shield" by the accumulation of protective compounds, carboxylic anions and polysaccharides, determined by both plants and microorganisms. 35231142 2 27 theme patterning 270:279 arg1 traits 293:298 patterning belowground traits 270:298 patterning belowground traits 270:298 However, the way N enrichment shapes plant microhabitats by patterning belowground traits and finally determines aboveground responses is poorly understood. 35231142 2 28 dep shapes 240:245 arg1 understood 355:364 understood 355:364 is poorly understood 345:364 However, the way N enrichment shapes plant microhabitats by patterning belowground traits and finally determines aboveground responses is poorly understood. 35231142 9 29 theme sensitive 1438:1446 arg1 roots 1432:1436 their roots 1426:1436 their roots sensitive to stresses induced by N enrichment 1426:1482 Conversely, forbs lacked the protective rhizosheaths which renders their roots sensitive to stresses induced by N enrichment, thus contributing to their disappearance under N-enriched conditions. 35231142 1 30 theme plant 105:109 arg1 traits 111:116 Belowground plant traits 93:116 Belowground plant traits 93:116 Belowground plant traits play important roles in plant diversity loss driven by atmospheric nitrogen (N) deposition. 35231142 7 31 theme biofilm-like 1121:1132 arg1 " 1140:1140 a "biofilm-like shield" 1118:1140 a "biofilm-like shield" 1118:1140 Rhizosheaths act as a "biofilm-like shield" by the accumulation of protective compounds, carboxylic anions and polysaccharides, determined by both plants and microorganisms. 35231142 7 31 theme biofilm-like 1121:1132 arg1 Rhizosheaths 1098:1109 Rhizosheaths 1098:1109 Rhizosheaths 1098:1109 Rhizosheaths act as a "biofilm-like shield" by the accumulation of protective compounds, carboxylic anions and polysaccharides, determined by both plants and microorganisms. 35231142 6 32 theme stress-avoiding 1044:1058 arg1 properties 1060:1069 the physicochemical, biological, and stress-avoiding properties 1007:1069 the physicochemical, biological, and stress-avoiding properties of their rhizosphere soil 1007:1095 Grasses also shaped a different microenvironment around their roots compared with forbs by affecting the physicochemical, biological, and stress-avoiding properties of their rhizosphere soil. 35231142 10 33 theme plant 1826:1830 arg1 loss 1842:1845 plant diversity loss 1826:1845 plant diversity loss caused by N deposition 1826:1868 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 2 34 theme aboveground 323:333 arg1 responses 335:343 aboveground responses 323:343 aboveground responses 323:343 However, the way N enrichment shapes plant microhabitats by patterning belowground traits and finally determines aboveground responses is poorly understood. 35231142 3 35 theme N-addition 440:449 arg1 experiments 462:472 seven N-addition simulation experiments 434:472 seven N-addition simulation experiments 434:472 Here, we investigated the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China. 35231142 0 36 theme trait-based 26:36 arg1 understanding 38:50 trait-based understanding 26:50 trait-based understanding of nitrogen-driven plant diversity loss 26:90 An integrated belowground trait-based understanding of nitrogen-driven plant diversity loss. 35231142 5 37 theme distinct 741:748 arg1 rhizosheaths 750:761 distinct rhizosheaths 741:761 distinct rhizosheaths 741:761 Compared with forb species, grass and sedge species exhibited distinct rhizosheaths; moreover, grasses and sedges expanded their rhizosheaths with increasing N-addition rate which allowed them to colonize belowground habitats. 35231142 3 38 theme grassland 490:498 arg1 ecosystems 500:509 multiple grassland ecosystems 481:509 multiple grassland ecosystems in China 481:518 Here, we investigated the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China. 35231142 3 39 theme rhizosheath 393:403 arg1 trait 405:409 the rhizosheath trait 389:409 the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China 389:518 Here, we investigated the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China. 35231142 6 40 theme different 928:936 arg1 microenvironment 938:953 a different microenvironment 926:953 a different microenvironment around their roots 926:972 Grasses also shaped a different microenvironment around their roots compared with forbs by affecting the physicochemical, biological, and stress-avoiding properties of their rhizosphere soil. 35231142 1 41 theme important 123:131 arg1 roles 133:137 important roles 123:137 important roles 123:137 Belowground plant traits play important roles in plant diversity loss driven by atmospheric nitrogen (N) deposition. 35231142 10 42 theme tolerance 1813:1821 arg1 contribution 1757:1768 the contribution 1753:1768 the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition 1753:1868 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 3 43 theme species 423:429 arg1 trait 405:409 the rhizosheath trait 389:409 the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China 389:518 Here, we investigated the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China. 35231142 6 44 theme biological 1028:1037 arg1 properties 1060:1069 the physicochemical, biological, and stress-avoiding properties 1007:1069 the physicochemical, biological, and stress-avoiding properties of their rhizosphere soil 1007:1095 Grasses also shaped a different microenvironment around their roots compared with forbs by affecting the physicochemical, biological, and stress-avoiding properties of their rhizosphere soil. 35231142 7 45 theme shield 1134:1139 arg1 " 1140:1140 a "biofilm-like shield" 1118:1140 a "biofilm-like shield" 1118:1140 Rhizosheaths act as a "biofilm-like shield" by the accumulation of protective compounds, carboxylic anions and polysaccharides, determined by both plants and microorganisms. 35231142 7 45 theme shield 1134:1139 arg1 Rhizosheaths 1098:1109 Rhizosheaths 1098:1109 Rhizosheaths 1098:1109 Rhizosheaths act as a "biofilm-like shield" by the accumulation of protective compounds, carboxylic anions and polysaccharides, determined by both plants and microorganisms. 35231142 10 46 theme environmental 1799:1811 arg1 tolerance 1813:1821 environmental tolerance 1799:1821 environmental tolerance 1799:1821 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 10 47 theme contribution 1757:1768 arg1 understanding 1736:1748 our mechanistic understanding 1720:1748 our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition 1720:1868 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 7 48 theme polysaccharides 1209:1223 arg1 accumulation 1149:1160 the accumulation 1145:1160 the accumulation of protective compounds, carboxylic anions and polysaccharides 1145:1223 Rhizosheaths act as a "biofilm-like shield" by the accumulation of protective compounds, carboxylic anions and polysaccharides, determined by both plants and microorganisms. 35231142 3 49 theme simulation 451:460 arg1 experiments 462:472 seven N-addition simulation experiments 434:472 seven N-addition simulation experiments 434:472 Here, we investigated the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China. 35231142 5 50 theme N-addition 837:846 arg1 rate 848:851 N-addition rate 837:851 N-addition rate which allowed them to colonize belowground habitats 837:903 Compared with forb species, grass and sedge species exhibited distinct rhizosheaths; moreover, grasses and sedges expanded their rhizosheaths with increasing N-addition rate which allowed them to colonize belowground habitats. 35231142 2 51 theme N 227:227 arg1 enrichment 229:238 the way N enrichment 219:238 the way N enrichment 219:238 However, the way N enrichment shapes plant microhabitats by patterning belowground traits and finally determines aboveground responses is poorly understood. 35231142 3 52 theme multiple 481:488 arg1 ecosystems 500:509 multiple grassland ecosystems 481:509 multiple grassland ecosystems in China 481:518 Here, we investigated the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China. 35231142 0 53 theme plant 71:75 arg1 loss 87:90 nitrogen-driven plant diversity loss 55:90 nitrogen-driven plant diversity loss 55:90 An integrated belowground trait-based understanding of nitrogen-driven plant diversity loss. 35231142 6 54 theme physicochemical 1011:1025 arg1 properties 1060:1069 the physicochemical, biological, and stress-avoiding properties 1007:1069 the physicochemical, biological, and stress-avoiding properties of their rhizosphere soil 1007:1095 Grasses also shaped a different microenvironment around their roots compared with forbs by affecting the physicochemical, biological, and stress-avoiding properties of their rhizosphere soil. 35231142 10 55 theme matching 1633:1640 arg1 trait 1627:1631 trait matching 1627:1640 trait matching 1627:1640 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 10 56 theme belowground 1598:1608 arg1 facilitation 1610:1621 belowground facilitation 1598:1621 belowground facilitation 1598:1621 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 2 57 theme way 223:225 arg1 enrichment 229:238 the way N enrichment 219:238 the way N enrichment 219:238 However, the way N enrichment shapes plant microhabitats by patterning belowground traits and finally determines aboveground responses is poorly understood. 35231142 0 58 theme nitrogen-driven 55:69 arg1 loss 87:90 nitrogen-driven plant diversity loss 55:90 nitrogen-driven plant diversity loss 55:90 An integrated belowground trait-based understanding of nitrogen-driven plant diversity loss. 35231142 4 59 theme functional 578:587 arg1 groups 589:594 plant functional groups 572:594 plant functional groups 572:594 We found that rhizosheath formation differed among plant functional groups and contributed to changes in plant community composition induced by N enrichment. 35231142 5 60 theme sedge 717:721 arg1 species 723:729 grass and sedge species 707:729 species 723:729 Compared with forb species, grass and sedge species exhibited distinct rhizosheaths; moreover, grasses and sedges expanded their rhizosheaths with increasing N-addition rate which allowed them to colonize belowground habitats. 35231142 4 61 theme plant 572:576 arg1 groups 589:594 plant functional groups 572:594 plant functional groups 572:594 We found that rhizosheath formation differed among plant functional groups and contributed to changes in plant community composition induced by N enrichment. 35231142 3 62 from ecosystems 500:509 arg1 China 514:518 China 514:518 China 514:518 Here, we investigated the rhizosheath trait of 74 plant species in seven N-addition simulation experiments across multiple grassland ecosystems in China. 35231142 1 63 theme plant 142:146 arg1 loss 158:161 plant diversity loss 142:161 plant diversity loss driven by atmospheric nitrogen (N) deposition 142:207 Belowground plant traits play important roles in plant diversity loss driven by atmospheric nitrogen (N) deposition. 35231142 9 64 theme N 1471:1471 arg1 enrichment 1473:1482 N enrichment 1471:1482 N enrichment 1471:1482 Conversely, forbs lacked the protective rhizosheaths which renders their roots sensitive to stresses induced by N enrichment, thus contributing to their disappearance under N-enriched conditions. 35231142 1 65 theme Belowground 93:103 arg1 traits 111:116 Belowground plant traits 93:116 Belowground plant traits 93:116 Belowground plant traits play important roles in plant diversity loss driven by atmospheric nitrogen (N) deposition. 35231142 1 66 theme diversity 148:156 arg1 loss 158:161 plant diversity loss 142:161 plant diversity loss driven by atmospheric nitrogen (N) deposition 142:207 Belowground plant traits play important roles in plant diversity loss driven by atmospheric nitrogen (N) deposition. 35231142 10 67 theme diversity 1832:1840 arg1 loss 1842:1845 plant diversity loss 1826:1845 plant diversity loss caused by N deposition 1826:1868 This study uncovers the processes by which belowground facilitation and trait matching affect aboveground responses under conditions of N enrichment, which advances our mechanistic understanding of the contribution of competitive exclusion and environmental tolerance to plant diversity loss caused by N deposition. 35231142 0 68 theme loss 87:90 arg1 understanding 38:50 trait-based understanding 26:50 trait-based understanding of nitrogen-driven plant diversity loss 26:90 An integrated belowground trait-based understanding of nitrogen-driven plant diversity loss. 35231142 2 69 theme plant 247:251 arg1 microhabitats 253:265 plant microhabitats 247:265 plant microhabitats 247:265 However, the way N enrichment shapes plant microhabitats by patterning belowground traits and finally determines aboveground responses is poorly understood. 35231142 5 70 theme belowground 884:894 arg1 habitats 896:903 belowground habitats 884:903 belowground habitats 884:903 Compared with forb species, grass and sedge species exhibited distinct rhizosheaths; moreover, grasses and sedges expanded their rhizosheaths with increasing N-addition rate which allowed them to colonize belowground habitats. 35231142 8 71 theme sedges 1315:1320 arg1 tolerance 1290:1298 the tolerance 1286:1298 the tolerance of grasses and sedges to stresses induced by N enrichment 1286:1356 This enhanced the tolerance of grasses and sedges to stresses induced by N enrichment. 35231142 4 72 theme N 665:665 arg1 enrichment 667:676 N enrichment 665:676 N enrichment 665:676 We found that rhizosheath formation differed among plant functional groups and contributed to changes in plant community composition induced by N enrichment. 35231142 0 73 theme diversity 77:85 arg1 loss 87:90 nitrogen-driven plant diversity loss 55:90 nitrogen-driven plant diversity loss 55:90 An integrated belowground trait-based understanding of nitrogen-driven plant diversity loss. 35231142 6 74 theme soil 1092:1095 arg1 properties 1060:1069 the physicochemical, biological, and stress-avoiding properties 1007:1069 the physicochemical, biological, and stress-avoiding properties of their rhizosphere soil 1007:1095 Grasses also shaped a different microenvironment around their roots compared with forbs by affecting the physicochemical, biological, and stress-avoiding properties of their rhizosphere soil. 37308732 3 0 theme PRPS1 721:725 arg1 activity 727:734 PRPS1 activity 721:734 PRPS1 activity 721:734 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 8 1 theme human 1227:1231 arg1 cancer 1253:1258 cancer 1253:1258 cancer 1253:1258 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 8 1 theme human 1227:1231 arg1 syndrome 1269:1276 Arts syndrome 1264:1276 Arts syndrome 1264:1276 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 8 1 theme human 1227:1231 arg1 diseases 1233:1240 human diseases 1227:1240 human diseases 1227:1240 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 1 2 theme metabolism 147:156 arg1 crossroads 124:133 the crossroads 120:133 the crossroads of cellular metabolism 120:156 O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. 37308732 4 3 theme PRPS1 808:812 arg1 phosphorylation 814:828 AMPK-mediated PRPS1 phosphorylation 794:828 AMPK-mediated PRPS1 phosphorylation 794:828 PRPS1 O-GlcNAcylation blocked AMPK binding and inhibited AMPK-mediated PRPS1 phosphorylation. 37308732 6 4 theme lung 992:995 arg1 cancer 997:1002 lung cancer 992:1002 lung cancer 992:1002 Elevated PRPS1 O-GlcNAcylation promotes tumorigenesis and confers resistance to chemoradiotherapy in lung cancer. 37308732 1 5 link O-linked 71:78 arg1 O-GlcNAc 104:111 O-GlcNAc 104:111 O-GlcNAc 104:111 O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. 37308732 1 5 link O-linked 71:78 arg1 glucosamine 91:101 O-linked β-N-acetyl glucosamine 71:101 O-linked β-N-acetyl glucosamine (O-GlcNAc) 71:112 O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. 37308732 8 6 theme direct 1152:1157 arg1 connection 1159:1168 a direct connection 1150:1168 a direct connection 1150:1168 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 3 7 theme de 516:517 arg1 pathway 545:551 the de novo nucleotide synthesis pathway 512:551 the de novo nucleotide synthesis pathway 512:551 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 3 8 theme pathway 545:551 arg1 pyrophosphate 458:470 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) 443:491 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) 443:491 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 3 8 theme pathway 545:551 arg1 enzyme 502:507 the key enzyme 494:507 the key enzyme of the de novo nucleotide synthesis pathway 494:551 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 8 9 theme Arts 1264:1267 arg1 syndrome 1269:1276 Arts syndrome 1264:1276 Arts syndrome 1264:1276 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 7 10 theme R196W 1049:1053 arg1 mutant 1055:1060 Arts-syndrome-associated PRPS1 R196W mutant 1018:1060 Arts-syndrome-associated PRPS1 R196W mutant 1018:1060 Furthermore, Arts-syndrome-associated PRPS1 R196W mutant exhibits decreased PRPS1 O-GlcNAcylation and activity. 37308732 2 11 theme nicotinamide 360:371 arg1 NAD 395:397 NAD 395:397 NAD 395:397 Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. 37308732 2 11 theme nicotinamide 360:371 arg1 dinucleotide 381:392 nicotinamide adenine dinucleotide 360:392 nicotinamide adenine dinucleotide (NAD) production 360:409 Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. 37308732 4 12 theme PRPS1 737:741 arg1 O-GlcNAcylation 743:757 PRPS1 O-GlcNAcylation 737:757 PRPS1 O-GlcNAcylation 737:757 PRPS1 O-GlcNAcylation blocked AMPK binding and inhibited AMPK-mediated PRPS1 phosphorylation. 37308732 1 13 theme O-linked 71:78 arg1 O-GlcNAc 104:111 O-GlcNAc 104:111 O-GlcNAc 104:111 O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. 37308732 1 13 theme O-linked 71:78 arg1 glucosamine 91:101 O-linked β-N-acetyl glucosamine 71:101 O-linked β-N-acetyl glucosamine (O-GlcNAc) 71:112 O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. 37308732 7 14 theme Arts-syndrome-associated 1018:1041 arg1 mutant 1055:1060 Arts-syndrome-associated PRPS1 R196W mutant 1018:1060 Arts-syndrome-associated PRPS1 R196W mutant 1018:1060 Furthermore, Arts-syndrome-associated PRPS1 R196W mutant exhibits decreased PRPS1 O-GlcNAcylation and activity. 37308732 1 15 theme β-N-acetyl 80:89 arg1 O-GlcNAc 104:111 O-GlcNAc 104:111 O-GlcNAc 104:111 O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. 37308732 1 15 theme β-N-acetyl 80:89 arg1 glucosamine 91:101 O-linked β-N-acetyl glucosamine 71:101 O-linked β-N-acetyl glucosamine (O-GlcNAc) 71:112 O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. 37308732 5 16 theme PRPS1 851:855 arg1 activity 857:864 PRPS1 activity 851:864 PRPS1 activity in AMPK-deficient cells 851:888 OGT still regulates PRPS1 activity in AMPK-deficient cells. 37308732 5 17 from activity 857:864 arg1 cells 884:888 AMPK-deficient cells 869:888 AMPK-deficient cells 869:888 OGT still regulates PRPS1 activity in AMPK-deficient cells. 37308732 7 18 theme PRPS1 1043:1047 arg1 mutant 1055:1060 Arts-syndrome-associated PRPS1 R196W mutant 1018:1060 Arts-syndrome-associated PRPS1 R196W mutant 1018:1060 Furthermore, Arts-syndrome-associated PRPS1 R196W mutant exhibits decreased PRPS1 O-GlcNAcylation and activity. 37308732 4 19 theme AMPK 767:770 arg1 binding 772:778 AMPK binding 767:778 AMPK binding 767:778 PRPS1 O-GlcNAcylation blocked AMPK binding and inhibited AMPK-mediated PRPS1 phosphorylation. 37308732 0 20 theme Direct 0:5 arg1 stimulation 7:17 Direct stimulation 0:17 Direct stimulation of de novo nucleotide synthesis by O-GlcNAcylation 0:68 Direct stimulation of de novo nucleotide synthesis by O-GlcNAcylation. 37308732 8 21 theme O-GlcNAc 1176:1183 arg1 cancer 1253:1258 cancer 1253:1258 cancer 1253:1258 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 8 21 theme O-GlcNAc 1176:1183 arg1 syndrome 1269:1276 Arts syndrome 1264:1276 Arts syndrome 1264:1276 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 8 21 theme O-GlcNAc 1176:1183 arg1 signals 1185:1191 O-GlcNAc signals 1176:1191 O-GlcNAc signals 1176:1191 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 2 22 dep de 327:328 arg1 novo 330:333 novo 330:333 novo 330:333 Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. 37308732 4 23 theme AMPK-mediated 794:806 arg1 phosphorylation 814:828 AMPK-mediated PRPS1 phosphorylation 794:828 AMPK-mediated PRPS1 phosphorylation 794:828 PRPS1 O-GlcNAcylation blocked AMPK binding and inhibited AMPK-mediated PRPS1 phosphorylation. 37308732 3 24 theme Phosphoribosyl 443:456 arg1 pyrophosphate 458:470 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) 443:491 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) 443:491 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 3 24 theme Phosphoribosyl 443:456 arg1 enzyme 502:507 the key enzyme 494:507 the key enzyme of the de novo nucleotide synthesis pathway 494:551 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 0 25 theme de 22:23 arg1 synthesis 41:49 de novo nucleotide synthesis 22:49 de novo nucleotide synthesis 22:49 Direct stimulation of de novo nucleotide synthesis by O-GlcNAcylation. 37308732 8 26 theme de 1194:1195 arg1 synthesis 1213:1221 de novo nucleotide synthesis 1194:1221 de novo nucleotide synthesis 1194:1221 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 3 27 dep de 516:517 arg1 novo 519:522 novo 519:522 novo 519:522 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 3 28 theme O-GlcNAc 575:582 arg1 OGT 597:599 OGT 597:599 OGT 597:599 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 3 28 theme O-GlcNAc 575:582 arg1 transferase 584:594 O-GlcNAc transferase 575:594 O-GlcNAc transferase (OGT) 575:600 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 6 29 theme PRPS1 900:904 arg1 O-GlcNAcylation 906:920 Elevated PRPS1 O-GlcNAcylation 891:920 Elevated PRPS1 O-GlcNAcylation 891:920 Elevated PRPS1 O-GlcNAcylation promotes tumorigenesis and confers resistance to chemoradiotherapy in lung cancer. 37308732 3 30 theme nucleotide 524:533 arg1 pathway 545:551 the de novo nucleotide synthesis pathway 512:551 the de novo nucleotide synthesis pathway 512:551 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 2 31 theme metabolic 425:433 arg1 states 435:440 abnormal metabolic states 416:440 abnormal metabolic states 416:440 Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. 37308732 0 32 theme nucleotide 30:39 arg1 synthesis 41:49 de novo nucleotide synthesis 22:49 de novo nucleotide synthesis 22:49 Direct stimulation of de novo nucleotide synthesis by O-GlcNAcylation. 37308732 8 33 theme nucleotide 1202:1211 arg1 synthesis 1213:1221 de novo nucleotide synthesis 1194:1221 de novo nucleotide synthesis 1194:1221 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 2 34 theme abnormal 416:423 arg1 states 435:440 abnormal metabolic states 416:440 abnormal metabolic states 416:440 Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. 37308732 3 35 theme hexamer 624:630 arg1 formation 632:640 PRPS1 hexamer formation 618:640 PRPS1 hexamer formation 618:640 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 8 36 dep de 1194:1195 arg1 novo 1197:1200 novo 1197:1200 novo 1197:1200 Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome. 37308732 6 37 from resistance 957:966 arg1 cancer 997:1002 lung cancer 992:1002 lung cancer 992:1002 Elevated PRPS1 O-GlcNAcylation promotes tumorigenesis and confers resistance to chemoradiotherapy in lung cancer. 37308732 3 38 dep pyrophosphate 458:470 arg1 synthetase 472:481 synthetase 1 472:483 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) 443:491 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 3 38 dep pyrophosphate 458:470 arg1 PRPS1 486:490 PRPS1 486:490 PRPS1 486:490 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 3 39 theme key 498:500 arg1 pyrophosphate 458:470 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) 443:491 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) 443:491 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 3 39 theme key 498:500 arg1 enzyme 502:507 the key enzyme 494:507 the key enzyme of the de novo nucleotide synthesis pathway 494:551 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 0 40 theme synthesis 41:49 arg1 stimulation 7:17 Direct stimulation 0:17 Direct stimulation of de novo nucleotide synthesis by O-GlcNAcylation 0:68 Direct stimulation of de novo nucleotide synthesis by O-GlcNAcylation. 37308732 3 41 theme feedback 683:690 arg1 inhibition 692:701 nucleotide product-mediated feedback inhibition 655:701 nucleotide product-mediated feedback inhibition 655:701 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 1 42 theme cellular 138:145 arg1 metabolism 147:156 cellular metabolism 138:156 cellular metabolism 138:156 O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. 37308732 2 43 theme nucleotide 335:344 arg1 synthesis 346:354 de novo nucleotide synthesis 327:354 de novo nucleotide synthesis 327:354 Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. 37308732 6 44 theme Elevated 891:898 arg1 O-GlcNAcylation 906:920 Elevated PRPS1 O-GlcNAcylation 891:920 Elevated PRPS1 O-GlcNAcylation 891:920 Elevated PRPS1 O-GlcNAcylation promotes tumorigenesis and confers resistance to chemoradiotherapy in lung cancer. 37308732 0 45 dep de 22:23 arg1 novo 25:28 novo 25:28 novo 25:28 Direct stimulation of de novo nucleotide synthesis by O-GlcNAcylation. 37308732 7 46 theme decreased 1071:1079 arg1 O-GlcNAcylation 1087:1101 decreased PRPS1 O-GlcNAcylation 1071:1101 decreased PRPS1 O-GlcNAcylation 1071:1101 Furthermore, Arts-syndrome-associated PRPS1 R196W mutant exhibits decreased PRPS1 O-GlcNAcylation and activity. 37308732 3 47 theme synthesis 535:543 arg1 pathway 545:551 the de novo nucleotide synthesis pathway 512:551 the de novo nucleotide synthesis pathway 512:551 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 3 48 theme nucleotide 655:664 arg1 inhibition 692:701 nucleotide product-mediated feedback inhibition 655:701 nucleotide product-mediated feedback inhibition 655:701 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 3 49 theme PRPS1 618:622 arg1 formation 632:640 PRPS1 hexamer formation 618:640 PRPS1 hexamer formation 618:640 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 2 50 theme de 327:328 arg1 synthesis 346:354 de novo nucleotide synthesis 327:354 de novo nucleotide synthesis 327:354 Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. 37308732 1 51 theme molecular 219:227 arg1 alterations 246:256 molecular and pathological alterations 219:256 molecular and pathological alterations that cause diseases 219:276 O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. 37308732 3 52 theme product-mediated 666:681 arg1 inhibition 692:701 nucleotide product-mediated feedback inhibition 655:701 nucleotide product-mediated feedback inhibition 655:701 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. 37308732 2 53 theme dinucleotide 381:392 arg1 production 400:409 nicotinamide adenine dinucleotide (NAD) production 360:409 nicotinamide adenine dinucleotide (NAD) production 360:409 Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. 37308732 5 54 theme AMPK-deficient 869:882 arg1 cells 884:888 AMPK-deficient cells 869:888 AMPK-deficient cells 869:888 OGT still regulates PRPS1 activity in AMPK-deficient cells. 37308732 7 55 theme PRPS1 1081:1085 arg1 O-GlcNAcylation 1087:1101 decreased PRPS1 O-GlcNAcylation 1071:1101 decreased PRPS1 O-GlcNAcylation 1071:1101 Furthermore, Arts-syndrome-associated PRPS1 R196W mutant exhibits decreased PRPS1 O-GlcNAcylation and activity. 37308732 2 56 theme adenine 373:379 arg1 NAD 395:397 NAD 395:397 NAD 395:397 Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. 37308732 2 56 theme adenine 373:379 arg1 dinucleotide 381:392 nicotinamide adenine dinucleotide 360:392 nicotinamide adenine dinucleotide (NAD) production 360:409 Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. 37308732 1 57 theme pathological 233:244 arg1 alterations 246:256 molecular and pathological alterations 219:256 molecular and pathological alterations that cause diseases 219:276 O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. 36240223 5 0 theme complex 733:739 arg1 samples 741:747 complex samples 733:747 complex samples 733:747 Based on the material prepared, we developed a workflow for site-specific analysis of O-GlcNAcylated proteins in complex samples. 36240223 0 1 theme Bonding 87:93 arg1 Interaction 95:105 Enhanced Hydrogen Bonding Interaction 69:105 Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis 69:127 Design and Preparation of Novel Nitro-Oxide-Grafted Nanospheres with Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis. 36240223 4 2 theme synthesized 558:568 arg1 material 570:577 the synthesized material 554:577 the synthesized material 554:577 By testing with synthetic O-GlcNAc peptides and standard proteins, the synthesized material exhibited high affinity and selectivity. 36240223 5 3 theme O-GlcNAcylated 706:719 arg1 proteins 721:728 O-GlcNAcylated proteins 706:728 O-GlcNAcylated proteins in complex samples 706:747 Based on the material prepared, we developed a workflow for site-specific analysis of O-GlcNAcylated proteins in complex samples. 36240223 7 4 theme PANC-1 941:946 arg1 cells 948:952 PANC-1 cells 941:952 PANC-1 cells 941:952 In total 364 O-GlcNAc peptides from 267 proteins were identified from PANC-1 cells. 36240223 0 5 theme O-GlcNAc 111:118 arg1 Analysis 120:127 O-GlcNAc Analysis 111:127 O-GlcNAc Analysis 111:127 Design and Preparation of Novel Nitro-Oxide-Grafted Nanospheres with Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis. 36240223 6 6 theme ductal 848:853 arg1 adenocarcinoma 855:868 pancreatic ductal adenocarcinoma 837:868 pancreatic ductal adenocarcinoma 837:868 We performed O-GlcNAc proteomics with the PANC-1 cell line, a representative model for pancreatic ductal adenocarcinoma. 36240223 5 7 theme proteins 721:728 arg1 analysis 694:701 site-specific analysis 680:701 site-specific analysis of O-GlcNAcylated proteins in complex samples 680:747 Based on the material prepared, we developed a workflow for site-specific analysis of O-GlcNAcylated proteins in complex samples. 36240223 6 8 theme representative 812:825 arg1 line 804:807 the PANC-1 cell line 788:807 the PANC-1 cell line 788:807 We performed O-GlcNAc proteomics with the PANC-1 cell line, a representative model for pancreatic ductal adenocarcinoma. 36240223 6 8 theme representative 812:825 arg1 model 827:831 a representative model 810:831 a representative model for pancreatic ductal adenocarcinoma 810:868 We performed O-GlcNAc proteomics with the PANC-1 cell line, a representative model for pancreatic ductal adenocarcinoma. 36240223 8 9 theme O-GlcNAc 1038:1045 arg1 sites 1047:1051 197 O-GlcNAc sites 1034:1051 197 O-GlcNAc sites newly reported 1034:1066 Among them, 183 proteins were newly found to be O-GlcNAcylated in humans (with 197 O-GlcNAc sites newly reported). 36240223 9 10 theme other 1161:1165 arg1 samples 1175:1181 other complex samples 1161:1181 other complex samples 1161:1181 The materials and methods can be facilely applied for site-specific O-GlcNAc proteomics in other complex samples. 36240223 4 11 theme O-GlcNAc 513:520 arg1 peptides 522:529 synthetic O-GlcNAc peptides 503:529 synthetic O-GlcNAc peptides 503:529 By testing with synthetic O-GlcNAc peptides and standard proteins, the synthesized material exhibited high affinity and selectivity. 36240223 8 12 theme 197 1034:1036 arg1 sites 1047:1051 197 O-GlcNAc sites 1034:1051 197 O-GlcNAc sites newly reported 1034:1066 Among them, 183 proteins were newly found to be O-GlcNAcylated in humans (with 197 O-GlcNAc sites newly reported). 36240223 4 13 theme standard 535:542 arg1 proteins 544:551 standard proteins 535:551 standard proteins 535:551 By testing with synthetic O-GlcNAc peptides and standard proteins, the synthesized material exhibited high affinity and selectivity. 36240223 0 14 theme Nitro-Oxide-Grafted 32:50 arg1 Nanospheres 52:62 Novel Nitro-Oxide-Grafted Nanospheres 26:62 Novel Nitro-Oxide-Grafted Nanospheres 26:62 Design and Preparation of Novel Nitro-Oxide-Grafted Nanospheres with Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis. 36240223 6 15 theme O-GlcNAc 763:770 arg1 proteomics 772:781 O-GlcNAc proteomics 763:781 O-GlcNAc proteomics 763:781 We performed O-GlcNAc proteomics with the PANC-1 cell line, a representative model for pancreatic ductal adenocarcinoma. 36240223 3 16 theme high 418:421 arg1 enrichment 432:441 high affinity enrichment 418:441 high affinity enrichment 418:441 Herein, an innovative material grafted with nitro-oxide (N→O) groups was designed for high affinity enrichment for O-GlcNAc peptides from native proteins. 36240223 5 17 theme site-specific 680:692 arg1 analysis 694:701 site-specific analysis 680:701 site-specific analysis of O-GlcNAcylated proteins in complex samples 680:747 Based on the material prepared, we developed a workflow for site-specific analysis of O-GlcNAcylated proteins in complex samples. 36240223 3 18 theme nitro-oxide 376:386 arg1 groups 394:399 nitro-oxide (N→O) groups 376:399 nitro-oxide (N→O) groups 376:399 Herein, an innovative material grafted with nitro-oxide (N→O) groups was designed for high affinity enrichment for O-GlcNAc peptides from native proteins. 36240223 9 19 theme O-GlcNAc 1138:1145 arg1 proteomics 1147:1156 site-specific O-GlcNAc proteomics 1124:1156 site-specific O-GlcNAc proteomics in other complex samples 1124:1181 The materials and methods can be facilely applied for site-specific O-GlcNAc proteomics in other complex samples. 36240223 3 20 theme affinity 423:430 arg1 enrichment 432:441 high affinity enrichment 418:441 high affinity enrichment 418:441 Herein, an innovative material grafted with nitro-oxide (N→O) groups was designed for high affinity enrichment for O-GlcNAc peptides from native proteins. 36240223 6 21 theme pancreatic 837:846 arg1 adenocarcinoma 855:868 pancreatic ductal adenocarcinoma 837:868 pancreatic ductal adenocarcinoma 837:868 We performed O-GlcNAc proteomics with the PANC-1 cell line, a representative model for pancreatic ductal adenocarcinoma. 36240223 3 22 theme native 470:475 arg1 proteins 477:484 native proteins 470:484 native proteins 470:484 Herein, an innovative material grafted with nitro-oxide (N→O) groups was designed for high affinity enrichment for O-GlcNAc peptides from native proteins. 36240223 5 23 from analysis 694:701 arg1 samples 741:747 complex samples 733:747 complex samples 733:747 Based on the material prepared, we developed a workflow for site-specific analysis of O-GlcNAcylated proteins in complex samples. 36240223 8 24 theme reported 1059:1066 arg1 sites 1047:1051 197 O-GlcNAc sites 1034:1051 197 O-GlcNAc sites newly reported 1034:1066 Among them, 183 proteins were newly found to be O-GlcNAcylated in humans (with 197 O-GlcNAc sites newly reported). 36240223 8 25 from humans 1021:1026 arg1 O-GlcNAcylated 1003:1016 O-GlcNAcylated 1003:1016 O-GlcNAcylated 1003:1016 Among them, 183 proteins were newly found to be O-GlcNAcylated in humans (with 197 O-GlcNAc sites newly reported). 36240223 7 26 theme O-GlcNAc 884:891 arg1 peptides 893:900 364 O-GlcNAc peptides 880:900 364 O-GlcNAc peptides from 267 proteins 880:918 In total 364 O-GlcNAc peptides from 267 proteins were identified from PANC-1 cells. 36240223 3 27 theme O-GlcNAc 447:454 arg1 peptides 456:463 O-GlcNAc peptides 447:463 O-GlcNAc peptides from native proteins 447:484 Herein, an innovative material grafted with nitro-oxide (N→O) groups was designed for high affinity enrichment for O-GlcNAc peptides from native proteins. 36240223 8 28 from O-GlcNAcylated 1003:1016 arg1 humans 1021:1026 humans 1021:1026 humans (with 197 O-GlcNAc sites newly reported) 1021:1067 Among them, 183 proteins were newly found to be O-GlcNAcylated in humans (with 197 O-GlcNAc sites newly reported). 36240223 2 29 theme site-specific 253:265 arg1 characterization 267:282 site-specific characterization 253:282 site-specific characterization of O-GlcNAcylated proteins 253:309 However, site-specific characterization of O-GlcNAcylated proteins remains challenging. 36240223 9 30 theme complex 1167:1173 arg1 samples 1175:1181 other complex samples 1161:1181 other complex samples 1161:1181 The materials and methods can be facilely applied for site-specific O-GlcNAc proteomics in other complex samples. 36240223 1 31 theme many 229:232 arg1 proteins 234:241 many proteins 229:241 many proteins 229:241 As an essential modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modulates the functions of many proteins. 36240223 0 32 theme Novel 26:30 arg1 Nanospheres 52:62 Novel Nitro-Oxide-Grafted Nanospheres 26:62 Novel Nitro-Oxide-Grafted Nanospheres 26:62 Design and Preparation of Novel Nitro-Oxide-Grafted Nanospheres with Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis. 36240223 5 33 from proteins 721:728 arg1 samples 741:747 complex samples 733:747 complex samples 733:747 Based on the material prepared, we developed a workflow for site-specific analysis of O-GlcNAcylated proteins in complex samples. 36240223 1 34 link O-linked 160:167 arg1 O-GlcNAc 192:199 O-GlcNAc 192:199 O-GlcNAc 192:199 As an essential modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modulates the functions of many proteins. 36240223 1 34 link O-linked 160:167 arg1 β-N-acetylglucosamine 169:189 O-linked β-N-acetylglucosamine 160:189 O-linked β-N-acetylglucosamine (O-GlcNAc) 160:200 As an essential modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modulates the functions of many proteins. 36240223 4 35 theme synthetic 503:511 arg1 peptides 522:529 synthetic O-GlcNAc peptides 503:529 synthetic O-GlcNAc peptides 503:529 By testing with synthetic O-GlcNAc peptides and standard proteins, the synthesized material exhibited high affinity and selectivity. 36240223 1 36 theme proteins 234:241 arg1 modification 146:157 an essential modification 133:157 an essential modification 133:157 As an essential modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modulates the functions of many proteins. 36240223 1 36 theme proteins 234:241 arg1 functions 216:224 the functions 212:224 the functions of many proteins 212:241 As an essential modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modulates the functions of many proteins. 36240223 3 37 theme innovative 343:352 arg1 material 354:361 an innovative material 340:361 an innovative material grafted with nitro-oxide (N→O) groups 340:399 Herein, an innovative material grafted with nitro-oxide (N→O) groups was designed for high affinity enrichment for O-GlcNAc peptides from native proteins. 36240223 9 38 from proteomics 1147:1156 arg1 samples 1175:1181 other complex samples 1161:1181 other complex samples 1161:1181 The materials and methods can be facilely applied for site-specific O-GlcNAc proteomics in other complex samples. 36240223 0 39 with Preparation 11:21 arg1 Interaction 95:105 Enhanced Hydrogen Bonding Interaction 69:105 Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis 69:127 Design and Preparation of Novel Nitro-Oxide-Grafted Nanospheres with Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis. 36240223 0 40 theme Nanospheres 52:62 arg1 Preparation 11:21 Preparation 11:21 Preparation 11:21 Design and Preparation of Novel Nitro-Oxide-Grafted Nanospheres with Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis. 36240223 0 40 theme Nanospheres 52:62 arg1 Design 0:5 Design 0:5 Design 0:5 Design and Preparation of Novel Nitro-Oxide-Grafted Nanospheres with Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis. 36240223 4 41 theme high 589:592 arg1 affinity 594:601 high affinity 589:601 high affinity 589:601 By testing with synthetic O-GlcNAc peptides and standard proteins, the synthesized material exhibited high affinity and selectivity. 36240223 7 42 from proteins 911:918 arg1 peptides 893:900 364 O-GlcNAc peptides 880:900 364 O-GlcNAc peptides from 267 proteins 880:918 In total 364 O-GlcNAc peptides from 267 proteins were identified from PANC-1 cells. 36240223 2 43 theme proteins 302:309 arg1 characterization 267:282 site-specific characterization 253:282 site-specific characterization of O-GlcNAcylated proteins 253:309 However, site-specific characterization of O-GlcNAcylated proteins remains challenging. 36240223 0 44 with Design 0:5 arg1 Interaction 95:105 Enhanced Hydrogen Bonding Interaction 69:105 Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis 69:127 Design and Preparation of Novel Nitro-Oxide-Grafted Nanospheres with Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis. 36240223 1 45 theme essential 136:144 arg1 modification 146:157 an essential modification 133:157 an essential modification 133:157 As an essential modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modulates the functions of many proteins. 36240223 1 45 theme essential 136:144 arg1 functions 216:224 the functions 212:224 the functions of many proteins 212:241 As an essential modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modulates the functions of many proteins. 36240223 6 46 theme PANC-1 792:797 arg1 line 804:807 the PANC-1 cell line 788:807 the PANC-1 cell line 788:807 We performed O-GlcNAc proteomics with the PANC-1 cell line, a representative model for pancreatic ductal adenocarcinoma. 36240223 6 46 theme PANC-1 792:797 arg1 model 827:831 a representative model 810:831 a representative model for pancreatic ductal adenocarcinoma 810:868 We performed O-GlcNAc proteomics with the PANC-1 cell line, a representative model for pancreatic ductal adenocarcinoma. 36240223 2 47 theme O-GlcNAcylated 287:300 arg1 proteins 302:309 O-GlcNAcylated proteins 287:309 O-GlcNAcylated proteins 287:309 However, site-specific characterization of O-GlcNAcylated proteins remains challenging. 36240223 8 48 with humans 1021:1026 arg1 sites 1047:1051 197 O-GlcNAc sites 1034:1051 197 O-GlcNAc sites newly reported 1034:1066 Among them, 183 proteins were newly found to be O-GlcNAcylated in humans (with 197 O-GlcNAc sites newly reported). 36240223 9 49 theme site-specific 1124:1136 arg1 proteomics 1147:1156 site-specific O-GlcNAc proteomics 1124:1156 site-specific O-GlcNAc proteomics in other complex samples 1124:1181 The materials and methods can be facilely applied for site-specific O-GlcNAc proteomics in other complex samples. 36240223 0 50 theme Hydrogen 78:85 arg1 Interaction 95:105 Enhanced Hydrogen Bonding Interaction 69:105 Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis 69:127 Design and Preparation of Novel Nitro-Oxide-Grafted Nanospheres with Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis. 36240223 6 51 theme cell 799:802 arg1 line 804:807 the PANC-1 cell line 788:807 the PANC-1 cell line 788:807 We performed O-GlcNAc proteomics with the PANC-1 cell line, a representative model for pancreatic ductal adenocarcinoma. 36240223 6 51 theme cell 799:802 arg1 model 827:831 a representative model 810:831 a representative model for pancreatic ductal adenocarcinoma 810:868 We performed O-GlcNAc proteomics with the PANC-1 cell line, a representative model for pancreatic ductal adenocarcinoma. 36240223 0 52 theme Enhanced 69:76 arg1 Interaction 95:105 Enhanced Hydrogen Bonding Interaction 69:105 Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis 69:127 Design and Preparation of Novel Nitro-Oxide-Grafted Nanospheres with Enhanced Hydrogen Bonding Interaction for O-GlcNAc Analysis. 36240223 3 53 from proteins 477:484 arg1 peptides 456:463 O-GlcNAc peptides 447:463 O-GlcNAc peptides from native proteins 447:484 Herein, an innovative material grafted with nitro-oxide (N→O) groups was designed for high affinity enrichment for O-GlcNAc peptides from native proteins. 36240223 1 54 theme O-linked 160:167 arg1 O-GlcNAc 192:199 O-GlcNAc 192:199 O-GlcNAc 192:199 As an essential modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modulates the functions of many proteins. 36240223 1 54 theme O-linked 160:167 arg1 β-N-acetylglucosamine 169:189 O-linked β-N-acetylglucosamine 160:189 O-linked β-N-acetylglucosamine (O-GlcNAc) 160:200 As an essential modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modulates the functions of many proteins. 36240223 5 55 from samples 741:747 arg1 analysis 694:701 site-specific analysis 680:701 site-specific analysis of O-GlcNAcylated proteins in complex samples 680:747 Based on the material prepared, we developed a workflow for site-specific analysis of O-GlcNAcylated proteins in complex samples. 36598936 7 0 theme O-GlcNAc 1292:1299 arg1 understanding 1275:1287 the manipulation and functional understanding 1243:1287 the manipulation and functional understanding of O-GlcNAc 1243:1299 The spatiotemporal control of O-GlcNAc through the chemically activatable OGA-intein fusion will facilitate the manipulation and functional understanding of O-GlcNAc in live cells. 36598936 0 1 from O-GlcNAcase 25:35 arg1 Cells 84:88 Live Cells 79:88 Live Cells 79:88 Small Molecule-Activated O-GlcNAcase for Spatiotemporal Removal of O-GlcNAc in Live Cells. 36598936 5 2 from 4-HT 915:918 arg1 manner 950:955 a time- and dose-dependent manner 923:955 a time- and dose-dependent manner 923:955 After rational protein engineering and optimization, we identified an OGA-intein variant whose deglycosidase activity can be triggered in the desired subcellular compartments by 4-HT in a time- and dose-dependent manner. 36598936 1 3 theme post-translational 156:173 arg1 N-acetylglucosamine 120:138 The nutrient sensor O-linked N-acetylglucosamine 91:138 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) 91:149 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 3 theme post-translational 156:173 arg1 modification 175:186 a post-translational modification 154:186 a post-translational modification found on thousands of nucleocytoplasmic proteins 154:235 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 4 4 theme live 633:636 arg1 cells 638:642 live cells 633:642 live cells 633:642 Here, we report a strategy for spatiotemporal reduction of O-GlcNAc in live cells by designing an O-GlcNAcase (OGA) fused to an intein triggered by 4-hydroxytamoxifen (4-HT). 36598936 5 5 theme OGA-intein 807:816 arg1 variant 818:824 an OGA-intein variant 804:824 an OGA-intein variant whose deglycosidase activity can be triggered in the desired subcellular compartments by 4-HT in a time- and dose-dependent manner 804:955 After rational protein engineering and optimization, we identified an OGA-intein variant whose deglycosidase activity can be triggered in the desired subcellular compartments by 4-HT in a time- and dose-dependent manner. 36598936 7 6 theme O-GlcNAc 1165:1172 arg1 control 1154:1160 The spatiotemporal control 1135:1160 The spatiotemporal control of O-GlcNAc through the chemically activatable OGA-intein fusion 1135:1225 The spatiotemporal control of O-GlcNAc through the chemically activatable OGA-intein fusion will facilitate the manipulation and functional understanding of O-GlcNAc in live cells. 36598936 6 7 from effects 1064:1070 arg1 cells 1089:1093 breast cancer cells 1075:1093 breast cancer cells 1075:1093 Finally, we demonstrated that 4-HT activation of the OGA-intein fusion can likewise potentiate inhibitory effects in breast cancer cells by virtue of the reduction of O-GlcNAc. 36598936 5 8 theme dose-dependent 935:948 arg1 manner 950:955 a time- and dose-dependent manner 923:955 a time- and dose-dependent manner 923:955 After rational protein engineering and optimization, we identified an OGA-intein variant whose deglycosidase activity can be triggered in the desired subcellular compartments by 4-HT in a time- and dose-dependent manner. 36598936 5 9 theme deglycosidase 832:844 arg1 activity 846:853 activity 846:853 activity 846:853 After rational protein engineering and optimization, we identified an OGA-intein variant whose deglycosidase activity can be triggered in the desired subcellular compartments by 4-HT in a time- and dose-dependent manner. 36598936 7 10 theme spatiotemporal 1139:1152 arg1 control 1154:1160 The spatiotemporal control 1135:1160 The spatiotemporal control of O-GlcNAc through the chemically activatable OGA-intein fusion 1135:1225 The spatiotemporal control of O-GlcNAc through the chemically activatable OGA-intein fusion will facilitate the manipulation and functional understanding of O-GlcNAc in live cells. 36598936 2 11 theme spatial 323:329 arg1 manner 331:336 a temporal and spatial manner 308:336 a temporal and spatial manner 308:336 O-GlcNAc levels in cells dynamically respond to environmental cues in a temporal and spatial manner, leading to altered signal transduction and functional effects. 36598936 3 12 theme O-GlcNAc 435:442 arg1 levels 444:449 O-GlcNAc levels 435:449 O-GlcNAc levels 435:449 The spatiotemporal regulation of O-GlcNAc levels would accelerate functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes. 36598936 2 13 theme temporal 310:317 arg1 manner 331:336 a temporal and spatial manner 308:336 a temporal and spatial manner 308:336 O-GlcNAc levels in cells dynamically respond to environmental cues in a temporal and spatial manner, leading to altered signal transduction and functional effects. 36598936 2 14 theme functional 382:391 arg1 effects 393:399 functional effects 382:399 functional effects 382:399 O-GlcNAc levels in cells dynamically respond to environmental cues in a temporal and spatial manner, leading to altered signal transduction and functional effects. 36598936 5 15 theme desired 879:885 arg1 compartments 899:910 the desired subcellular compartments 875:910 the desired subcellular compartments 875:910 After rational protein engineering and optimization, we identified an OGA-intein variant whose deglycosidase activity can be triggered in the desired subcellular compartments by 4-HT in a time- and dose-dependent manner. 36598936 3 16 theme cell 525:528 arg1 behaviors 530:538 cell behaviors 525:538 cell behaviors 525:538 The spatiotemporal regulation of O-GlcNAc levels would accelerate functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes. 36598936 2 17 from levels 247:252 arg1 cells 257:261 cells 257:261 cells 257:261 O-GlcNAc levels in cells dynamically respond to environmental cues in a temporal and spatial manner, leading to altered signal transduction and functional effects. 36598936 6 18 theme O-GlcNAc 1125:1132 arg1 reduction 1112:1120 the reduction 1108:1120 the reduction of O-GlcNAc 1108:1132 Finally, we demonstrated that 4-HT activation of the OGA-intein fusion can likewise potentiate inhibitory effects in breast cancer cells by virtue of the reduction of O-GlcNAc. 36598936 7 19 theme functional 1264:1273 arg1 understanding 1275:1287 the manipulation and functional understanding 1243:1287 the manipulation and functional understanding of O-GlcNAc 1243:1299 The spatiotemporal control of O-GlcNAc through the chemically activatable OGA-intein fusion will facilitate the manipulation and functional understanding of O-GlcNAc in live cells. 36598936 6 20 theme inhibitory 1053:1062 arg1 effects 1064:1070 inhibitory effects 1053:1070 inhibitory effects in breast cancer cells 1053:1093 Finally, we demonstrated that 4-HT activation of the OGA-intein fusion can likewise potentiate inhibitory effects in breast cancer cells by virtue of the reduction of O-GlcNAc. 36598936 6 21 theme breast 1075:1080 arg1 cells 1089:1093 breast cancer cells 1075:1093 breast cancer cells 1075:1093 Finally, we demonstrated that 4-HT activation of the OGA-intein fusion can likewise potentiate inhibitory effects in breast cancer cells by virtue of the reduction of O-GlcNAc. 36598936 3 22 theme O-GlcNAc 496:503 arg1 interrogation 479:491 functional interrogation 468:491 functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes 468:559 The spatiotemporal regulation of O-GlcNAc levels would accelerate functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes. 36598936 0 23 theme Molecule-Activated 6:23 arg1 O-GlcNAcase 25:35 Small Molecule-Activated O-GlcNAcase 0:35 Small Molecule-Activated O-GlcNAcase for Spatiotemporal Removal of O-GlcNAc in Live Cells 0:88 Small Molecule-Activated O-GlcNAcase for Spatiotemporal Removal of O-GlcNAc in Live Cells. 36598936 7 24 theme live 1304:1307 arg1 cells 1309:1313 live cells 1304:1313 live cells 1304:1313 The spatiotemporal control of O-GlcNAc through the chemically activatable OGA-intein fusion will facilitate the manipulation and functional understanding of O-GlcNAc in live cells. 36598936 6 25 theme reduction 1112:1120 arg1 virtue 1098:1103 virtue 1098:1103 virtue of the reduction of O-GlcNAc 1098:1132 Finally, we demonstrated that 4-HT activation of the OGA-intein fusion can likewise potentiate inhibitory effects in breast cancer cells by virtue of the reduction of O-GlcNAc. 36598936 3 26 theme functional 468:477 arg1 interrogation 479:491 functional interrogation 468:491 functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes 468:559 The spatiotemporal regulation of O-GlcNAc levels would accelerate functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes. 36598936 0 27 theme Small 0:4 arg1 O-GlcNAcase 25:35 Small Molecule-Activated O-GlcNAcase 0:35 Small Molecule-Activated O-GlcNAcase for Spatiotemporal Removal of O-GlcNAc in Live Cells 0:88 Small Molecule-Activated O-GlcNAcase for Spatiotemporal Removal of O-GlcNAc in Live Cells. 36598936 6 28 theme fusion 1022:1027 arg1 activation 993:1002 4-HT activation 988:1002 4-HT activation of the OGA-intein fusion 988:1027 Finally, we demonstrated that 4-HT activation of the OGA-intein fusion can likewise potentiate inhibitory effects in breast cancer cells by virtue of the reduction of O-GlcNAc. 36598936 1 29 theme nutrient 95:102 arg1 O-GlcNAc 141:148 O-GlcNAc 141:148 O-GlcNAc 141:148 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 29 theme nutrient 95:102 arg1 N-acetylglucosamine 120:138 The nutrient sensor O-linked N-acetylglucosamine 91:138 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) 91:149 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 29 theme nutrient 95:102 arg1 modification 175:186 a post-translational modification 154:186 a post-translational modification found on thousands of nucleocytoplasmic proteins 154:235 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 4 30 from reduction 608:616 arg1 cells 638:642 live cells 633:642 live cells 633:642 Here, we report a strategy for spatiotemporal reduction of O-GlcNAc in live cells by designing an O-GlcNAcase (OGA) fused to an intein triggered by 4-hydroxytamoxifen (4-HT). 36598936 4 31 theme spatiotemporal 593:606 arg1 reduction 608:616 spatiotemporal reduction 593:616 spatiotemporal reduction of O-GlcNAc in live cells 593:642 Here, we report a strategy for spatiotemporal reduction of O-GlcNAc in live cells by designing an O-GlcNAcase (OGA) fused to an intein triggered by 4-hydroxytamoxifen (4-HT). 36598936 1 32 theme sensor 104:109 arg1 O-GlcNAc 141:148 O-GlcNAc 141:148 O-GlcNAc 141:148 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 32 theme sensor 104:109 arg1 N-acetylglucosamine 120:138 The nutrient sensor O-linked N-acetylglucosamine 91:138 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) 91:149 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 32 theme sensor 104:109 arg1 modification 175:186 a post-translational modification 154:186 a post-translational modification found on thousands of nucleocytoplasmic proteins 154:235 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 33 theme nucleocytoplasmic 210:226 arg1 proteins 228:235 nucleocytoplasmic proteins 210:235 nucleocytoplasmic proteins 210:235 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 3 34 theme spatiotemporal 406:419 arg1 regulation 421:430 The spatiotemporal regulation 402:430 The spatiotemporal regulation of O-GlcNAc levels 402:449 The spatiotemporal regulation of O-GlcNAc levels would accelerate functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes. 36598936 4 35 theme O-GlcNAc 621:628 arg1 reduction 608:616 spatiotemporal reduction 593:616 spatiotemporal reduction of O-GlcNAc in live cells 593:642 Here, we report a strategy for spatiotemporal reduction of O-GlcNAc in live cells by designing an O-GlcNAcase (OGA) fused to an intein triggered by 4-hydroxytamoxifen (4-HT). 36598936 1 36 theme O-linked 111:118 arg1 O-GlcNAc 141:148 O-GlcNAc 141:148 O-GlcNAc 141:148 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 36 theme O-linked 111:118 arg1 N-acetylglucosamine 120:138 The nutrient sensor O-linked N-acetylglucosamine 91:138 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) 91:149 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 36 theme O-linked 111:118 arg1 modification 175:186 a post-translational modification 154:186 a post-translational modification found on thousands of nucleocytoplasmic proteins 154:235 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 37 theme proteins 228:235 arg1 thousands 197:205 thousands 197:205 thousands of nucleocytoplasmic proteins 197:235 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 7 38 theme OGA-intein 1209:1218 arg1 fusion 1220:1225 the chemically activatable OGA-intein fusion 1182:1225 the chemically activatable OGA-intein fusion 1182:1225 The spatiotemporal control of O-GlcNAc through the chemically activatable OGA-intein fusion will facilitate the manipulation and functional understanding of O-GlcNAc in live cells. 36598936 5 39 theme rational 743:750 arg1 engineering 760:770 rational protein engineering 743:770 rational protein engineering 743:770 After rational protein engineering and optimization, we identified an OGA-intein variant whose deglycosidase activity can be triggered in the desired subcellular compartments by 4-HT in a time- and dose-dependent manner. 36598936 1 40 located found 188:192 arg1 thousands 197:205 thousands 197:205 thousands of nucleocytoplasmic proteins 197:235 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 40 located found 188:192 arg2 modification 175:186 a post-translational modification 154:186 a post-translational modification found on thousands of nucleocytoplasmic proteins 154:235 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 40 located found 188:192 arg2 N-acetylglucosamine 120:138 The nutrient sensor O-linked N-acetylglucosamine 91:138 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) 91:149 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 5 41 theme subcellular 887:897 arg1 compartments 899:910 the desired subcellular compartments 875:910 the desired subcellular compartments 875:910 After rational protein engineering and optimization, we identified an OGA-intein variant whose deglycosidase activity can be triggered in the desired subcellular compartments by 4-HT in a time- and dose-dependent manner. 36598936 0 42 theme Spatiotemporal 41:54 arg1 Removal 56:62 Spatiotemporal Removal 41:62 Spatiotemporal Removal of O-GlcNAc 41:74 Small Molecule-Activated O-GlcNAcase for Spatiotemporal Removal of O-GlcNAc in Live Cells. 36598936 5 43 theme protein 752:758 arg1 engineering 760:770 rational protein engineering 743:770 rational protein engineering 743:770 After rational protein engineering and optimization, we identified an OGA-intein variant whose deglycosidase activity can be triggered in the desired subcellular compartments by 4-HT in a time- and dose-dependent manner. 36598936 3 44 theme manipulation 509:520 arg1 interrogation 479:491 functional interrogation 468:491 functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes 468:559 The spatiotemporal regulation of O-GlcNAc levels would accelerate functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes. 36598936 0 45 theme O-GlcNAc 67:74 arg1 Removal 56:62 Spatiotemporal Removal 41:62 Spatiotemporal Removal of O-GlcNAc 41:74 Small Molecule-Activated O-GlcNAcase for Spatiotemporal Removal of O-GlcNAc in Live Cells. 36598936 6 46 theme 4-HT 988:991 arg1 activation 993:1002 4-HT activation 988:1002 4-HT activation of the OGA-intein fusion 988:1027 Finally, we demonstrated that 4-HT activation of the OGA-intein fusion can likewise potentiate inhibitory effects in breast cancer cells by virtue of the reduction of O-GlcNAc. 36598936 6 47 theme OGA-intein 1011:1020 arg1 fusion 1022:1027 the OGA-intein fusion 1007:1027 the OGA-intein fusion 1007:1027 Finally, we demonstrated that 4-HT activation of the OGA-intein fusion can likewise potentiate inhibitory effects in breast cancer cells by virtue of the reduction of O-GlcNAc. 36598936 3 48 theme desired 544:550 arg1 outcomes 552:559 desired outcomes 544:559 desired outcomes 544:559 The spatiotemporal regulation of O-GlcNAc levels would accelerate functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes. 36598936 3 49 theme levels 444:449 arg1 regulation 421:430 The spatiotemporal regulation 402:430 The spatiotemporal regulation of O-GlcNAc levels 402:449 The spatiotemporal regulation of O-GlcNAc levels would accelerate functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes. 36598936 2 50 theme O-GlcNAc 238:245 arg1 levels 247:252 O-GlcNAc levels 238:252 O-GlcNAc levels in cells 238:261 O-GlcNAc levels in cells dynamically respond to environmental cues in a temporal and spatial manner, leading to altered signal transduction and functional effects. 36598936 2 51 theme signal 358:363 arg1 transduction 365:376 altered signal transduction 350:376 altered signal transduction 350:376 O-GlcNAc levels in cells dynamically respond to environmental cues in a temporal and spatial manner, leading to altered signal transduction and functional effects. 36598936 7 52 theme activatable 1197:1207 arg1 fusion 1220:1225 the chemically activatable OGA-intein fusion 1182:1225 the chemically activatable OGA-intein fusion 1182:1225 The spatiotemporal control of O-GlcNAc through the chemically activatable OGA-intein fusion will facilitate the manipulation and functional understanding of O-GlcNAc in live cells. 36598936 2 53 theme altered 350:356 arg1 transduction 365:376 altered signal transduction 350:376 altered signal transduction 350:376 O-GlcNAc levels in cells dynamically respond to environmental cues in a temporal and spatial manner, leading to altered signal transduction and functional effects. 36598936 6 54 theme cancer 1082:1087 arg1 cells 1089:1093 breast cancer cells 1075:1093 breast cancer cells 1075:1093 Finally, we demonstrated that 4-HT activation of the OGA-intein fusion can likewise potentiate inhibitory effects in breast cancer cells by virtue of the reduction of O-GlcNAc. 36598936 2 55 theme environmental 286:298 arg1 cues 300:303 environmental cues 286:303 environmental cues 286:303 O-GlcNAc levels in cells dynamically respond to environmental cues in a temporal and spatial manner, leading to altered signal transduction and functional effects. 36598936 3 56 theme behaviors 530:538 arg1 manipulation 509:520 manipulation 509:520 manipulation 509:520 The spatiotemporal regulation of O-GlcNAc levels would accelerate functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes. 36598936 3 56 theme behaviors 530:538 arg1 O-GlcNAc 496:503 O-GlcNAc 496:503 O-GlcNAc 496:503 The spatiotemporal regulation of O-GlcNAc levels would accelerate functional interrogation of O-GlcNAc and manipulation of cell behaviors for desired outcomes. 36598936 0 57 theme Live 79:82 arg1 Cells 84:88 Live Cells 79:88 Live Cells 79:88 Small Molecule-Activated O-GlcNAcase for Spatiotemporal Removal of O-GlcNAc in Live Cells. 36598936 5 58 theme time- 925:929 arg1 manner 950:955 a time- and dose-dependent manner 923:955 a time- and dose-dependent manner 923:955 After rational protein engineering and optimization, we identified an OGA-intein variant whose deglycosidase activity can be triggered in the desired subcellular compartments by 4-HT in a time- and dose-dependent manner. 36598936 1 59 link O-linked 111:118 arg1 O-GlcNAc 141:148 O-GlcNAc 141:148 O-GlcNAc 141:148 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 59 link O-linked 111:118 arg1 N-acetylglucosamine 120:138 The nutrient sensor O-linked N-acetylglucosamine 91:138 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) 91:149 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 1 59 link O-linked 111:118 arg1 modification 175:186 a post-translational modification 154:186 a post-translational modification found on thousands of nucleocytoplasmic proteins 154:235 The nutrient sensor O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification found on thousands of nucleocytoplasmic proteins. 36598936 7 60 theme manipulation 1247:1258 arg1 understanding 1275:1287 the manipulation and functional understanding 1243:1287 the manipulation and functional understanding of O-GlcNAc 1243:1299 The spatiotemporal control of O-GlcNAc through the chemically activatable OGA-intein fusion will facilitate the manipulation and functional understanding of O-GlcNAc in live cells. 35312780 9 0 theme sugar 1868:1872 arg1 receptors 1874:1882 blood group active sugar receptors 1849:1882 blood group active sugar receptors 1849:1882 Some modifications are located near amino acid side chains involved in the binding of blood group active sugar receptors. 35312780 3 1 theme vaccine 495:501 arg1 development 503:513 vaccine development 495:513 vaccine development 495:513 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 8 2 theme immunodominant 1671:1684 arg1 epitopes 1694:1701 immunodominant surface epitopes 1671:1701 immunodominant surface epitopes 1671:1701 Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. 35312780 1 3 theme non-enveloped 257:269 arg1 viruses 271:277 non-enveloped viruses 257:277 non-enveloped viruses 257:277 Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. 35312780 4 4 theme baculovirus 848:858 arg1 vector 860:865 the baculovirus vector 844:865 the baculovirus vector in H5 insect cells 844:884 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 3 5 theme development 503:513 arg1 context 484:490 the context 480:490 the context of vaccine development based on virus-like particles (VLPs) 480:550 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 8 6 theme capsid 1621:1626 arg1 proteins 1628:1635 virus capsid proteins 1615:1635 virus capsid proteins 1615:1635 Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. 35312780 8 7 theme epitopes 1694:1701 arg1 modulation 1657:1666 a modulation 1655:1666 a modulation of immunodominant surface epitopes 1655:1701 Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. 35312780 7 8 theme chromatography-mass 1403:1421 arg1 spectrometry 1423:1434 gas chromatography-mass spectrometry 1399:1434 gas chromatography-mass spectrometry 1399:1434 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 6 9 contain carry 1316:1320 arg1 Thr65 1231:1235 Thr65 1231:1235 Thr65 1231:1235 Thr65, Ser67, and Thr350 were revealed by liquid chromatography-mass spectrometry to carry HexNAc or Hex-HexNAc modifications, respectively. 35312780 6 9 contain carry 1316:1320 arg2 modifications 1343:1355 HexNAc or Hex-HexNAc modifications 1322:1355 HexNAc or Hex-HexNAc modifications 1322:1355 Thr65, Ser67, and Thr350 were revealed by liquid chromatography-mass spectrometry to carry HexNAc or Hex-HexNAc modifications, respectively. 35312780 6 9 contain carry 1316:1320 arg1 Ser67 1238:1242 Ser67 1238:1242 Ser67 1238:1242 Thr65, Ser67, and Thr350 were revealed by liquid chromatography-mass spectrometry to carry HexNAc or Hex-HexNAc modifications, respectively. 35312780 6 9 contain carry 1316:1320 arg1 Thr350 1249:1254 Thr350 1249:1254 Thr350 1249:1254 Thr65, Ser67, and Thr350 were revealed by liquid chromatography-mass spectrometry to carry HexNAc or Hex-HexNAc modifications, respectively. 35312780 3 10 theme VLPs 700:703 arg1 use 693:695 the use 689:695 the use of VLPs that were produced as secretory products in insect cells 689:760 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 3 11 theme virus-like 524:533 arg1 particles 535:543 virus-like particles 524:543 virus-like particles (VLPs) 524:550 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 3 11 theme virus-like 524:533 arg1 VLPs 546:549 VLPs 546:549 VLPs 546:549 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 1 12 theme surface 190:196 arg1 proteins 198:205 surface proteins 190:205 surface proteins of most enveloped viruses 190:231 Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. 35312780 5 13 theme peptides 1036:1043 arg1 analysis 1012:1019 Mass spectrometric analysis 993:1019 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine 993:1114 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 8 14 theme vaccine 1747:1753 arg1 design 1755:1760 anti-norovirus vaccine design 1732:1760 anti-norovirus vaccine design 1732:1760 Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. 35312780 1 15 theme enveloped 215:223 arg1 viruses 225:231 most enveloped viruses 210:231 most enveloped viruses 210:231 Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. 35312780 3 16 theme insect 749:754 arg1 cells 756:760 insect cells 749:760 insect cells 749:760 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 0 17 theme lectin 145:150 arg1 activity 152:159 lectin activity 145:159 lectin activity 145:159 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 4 18 theme insect 873:878 arg1 cells 880:884 H5 insect cells 870:884 H5 insect cells 870:884 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 5 19 theme P2 1208:1209 arg1 domain 1211:1216 the P2 domain 1204:1216 the P2 domain as modified 1204:1228 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 5 20 theme tryptic 1024:1030 arg1 peptides 1036:1043 tryptic VP1 peptides 1024:1043 tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine 1024:1114 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 4 21 gly glycosylated 893:904 arg1 VLPs 805:808 recombinant VLPs 793:808 recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells 793:884 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 4 21 gly glycosylated 893:904 arg2 VLPs 805:808 recombinant VLPs 793:808 recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells 793:884 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 4 21 gly glycosylated 893:904 arg1 domains 924:930 the protruding domains 909:930 the protruding domains that are involved in receptor binding and immune reactivity 909:990 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 3 22 theme potential 596:604 arg1 applications 634:645 potential prophylactic or therapeutic applications 596:645 potential prophylactic or therapeutic applications 596:645 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 7 23 theme O-linked 1547:1554 arg1 GlcNAc 1556:1561 O-linked GlcNAc 1547:1561 O-linked GlcNAc 1547:1561 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 0 24 theme H5 62:63 arg1 cells 72:76 H5 insect cells 62:76 H5 insect cells 62:76 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 5 25 theme % 1103:1103 arg1 ethylamine 1105:1114 70% ethylamine 1101:1114 70% ethylamine 1101:1114 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 0 26 theme post-translational 87:104 arg1 modifications 106:118 post-translational modifications 87:118 post-translational modifications 87:118 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 5 27 theme Michael 1081:1087 arg1 addition 1089:1096 beta-elimination Michael addition 1064:1096 beta-elimination Michael addition in 70% ethylamine 1064:1114 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 3 28 from products 737:744 arg1 cells 756:760 insect cells 749:760 insect cells 749:760 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 7 29 link O-linked 1547:1554 arg1 GlcNAc 1556:1561 O-linked GlcNAc 1547:1561 O-linked GlcNAc 1547:1561 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 0 30 theme Recombinant 0:10 arg1 GII.4 42:46 GII.4 42:46 GII.4 42:46 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 0 30 theme Recombinant 0:10 arg1 VP1 37:39 Recombinant norovirus capsid protein VP1 0:39 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells 0:76 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 4 31 from vector 860:865 arg1 cells 880:884 H5 insect cells 870:884 H5 insect cells 870:884 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 9 32 theme acid 1805:1808 arg1 chains 1815:1820 amino acid side chains 1799:1820 amino acid side chains involved in the binding of blood group active sugar receptors 1799:1882 Some modifications are located near amino acid side chains involved in the binding of blood group active sugar receptors. 35312780 2 33 theme capsid 422:427 arg1 VP1 438:440 VP1 438:440 VP1 438:440 Noroviruses belong to the latter group and are known to express one major capsid protein (VP1) that lacks genuine glycosylation. 35312780 2 33 theme capsid 422:427 arg1 protein 429:435 one major capsid protein 412:435 one major capsid protein (VP1) that lacks genuine glycosylation 412:474 Noroviruses belong to the latter group and are known to express one major capsid protein (VP1) that lacks genuine glycosylation. 35312780 0 34 theme capsid 22:27 arg1 GII.4 42:46 GII.4 42:46 GII.4 42:46 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 0 34 theme capsid 22:27 arg1 VP1 37:39 Recombinant norovirus capsid protein VP1 0:39 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells 0:76 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 3 35 theme increasing 650:659 arg1 number 661:666 an increasing number 647:666 an increasing number of reports 647:677 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 6 36 theme Hex-HexNAc 1332:1341 arg1 modifications 1343:1355 HexNAc or Hex-HexNAc modifications 1322:1355 HexNAc or Hex-HexNAc modifications 1322:1355 Thr65, Ser67, and Thr350 were revealed by liquid chromatography-mass spectrometry to carry HexNAc or Hex-HexNAc modifications, respectively. 35312780 4 37 theme receptor 953:960 arg1 binding 962:968 receptor binding 953:968 receptor binding 953:968 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 4 38 theme immune 974:979 arg1 reactivity 981:990 immune reactivity 974:990 immune reactivity 974:990 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 6 39 theme HexNAc 1322:1327 arg1 modifications 1343:1355 HexNAc or Hex-HexNAc modifications 1322:1355 HexNAc or Hex-HexNAc modifications 1322:1355 Thr65, Ser67, and Thr350 were revealed by liquid chromatography-mass spectrometry to carry HexNAc or Hex-HexNAc modifications, respectively. 35312780 5 40 theme spectrometric 998:1010 arg1 analysis 1012:1019 Mass spectrometric analysis 993:1019 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine 993:1114 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 8 41 theme proteins 1628:1635 arg1 modifications 1598:1610 Post-translational modifications 1579:1610 Post-translational modifications of virus capsid proteins 1579:1635 Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. 35312780 1 42 theme viruses 225:231 arg1 proteins 198:205 surface proteins 190:205 surface proteins of most enveloped viruses 190:231 Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. 35312780 9 43 theme blood 1849:1853 arg1 receptors 1874:1882 blood group active sugar receptors 1849:1882 blood group active sugar receptors 1849:1882 Some modifications are located near amino acid side chains involved in the binding of blood group active sugar receptors. 35312780 0 44 from impact 135:140 arg1 activity 152:159 lectin activity 145:159 lectin activity 145:159 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 0 44 from impact 135:140 arg1 design 173:178 vaccine design 165:178 vaccine design 165:178 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 7 45 attach presence 1450:1457 arg1 protein 1476:1482 VLP protein 1472:1482 VLP protein 1472:1482 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 7 45 attach presence 1450:1457 arg2 GlcNAc 1462:1467 GlcNAc 1462:1467 GlcNAc 1462:1467 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 9 46 theme active 1861:1866 arg1 receptors 1874:1882 blood group active sugar receptors 1849:1882 blood group active sugar receptors 1849:1882 Some modifications are located near amino acid side chains involved in the binding of blood group active sugar receptors. 35312780 9 47 theme receptors 1874:1882 arg1 binding 1838:1844 the binding 1834:1844 the binding of blood group active sugar receptors 1834:1882 Some modifications are located near amino acid side chains involved in the binding of blood group active sugar receptors. 35312780 7 48 theme gas 1399:1401 arg1 spectrometry 1423:1434 gas chromatography-mass spectrometry 1399:1434 gas chromatography-mass spectrometry 1399:1434 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 7 49 theme Monosaccharide 1372:1385 arg1 analysis 1387:1394 Monosaccharide analysis 1372:1394 Monosaccharide analysis by gas chromatography-mass spectrometry 1372:1434 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 8 50 theme virus 1615:1619 arg1 proteins 1628:1635 virus capsid proteins 1615:1635 virus capsid proteins 1615:1635 Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. 35312780 1 51 from glycoproteins 296:308 arg1 capsid 319:324 their capsid 313:324 their capsid as infective virions 313:345 Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. 35312780 8 52 theme surface 1686:1692 arg1 epitopes 1694:1701 immunodominant surface epitopes 1671:1701 immunodominant surface epitopes 1671:1701 Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. 35312780 6 53 theme chromatography-mass 1280:1298 arg1 spectrometry 1300:1311 liquid chromatography-mass spectrometry 1273:1311 liquid chromatography-mass spectrometry 1273:1311 Thr65, Ser67, and Thr350 were revealed by liquid chromatography-mass spectrometry to carry HexNAc or Hex-HexNAc modifications, respectively. 35312780 0 54 theme potential 125:133 arg1 impact 135:140 potential impact 125:140 potential impact on lectin activity and vaccine design 125:178 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 3 55 theme secretory 727:735 arg1 products 737:744 secretory products 727:744 secretory products in insect cells 727:760 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 3 55 theme secretory 727:735 arg1 VLPs 700:703 VLPs 700:703 VLPs that were produced as secretory products in insect cells 700:760 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 3 56 theme food 572:575 arg1 additives 577:585 food additives 572:585 food additives offering potential prophylactic or therapeutic applications 572:645 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 7 57 with immunoassays 1493:1504 arg1 antibodies 1523:1532 antibodies 1523:1532 antibodies 1523:1532 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 7 57 with immunoassays 1493:1504 arg1 lectins 1511:1517 lectins 1511:1517 lectins 1511:1517 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 1 58 theme most 210:213 arg1 viruses 225:231 most enveloped viruses 210:231 most enveloped viruses 210:231 Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. 35312780 8 59 theme anti-norovirus 1732:1745 arg1 design 1755:1760 anti-norovirus vaccine design 1732:1760 anti-norovirus vaccine design 1732:1760 Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. 35312780 7 60 from presence 1450:1457 arg1 protein 1476:1482 VLP protein 1472:1482 VLP protein 1472:1482 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 7 61 theme VP1 1566:1568 arg1 protein 1570:1576 VP1 protein 1566:1576 VP1 protein 1566:1576 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 0 62 theme vaccine 165:171 arg1 design 173:178 vaccine design 165:178 vaccine design 165:178 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 3 63 theme prophylactic 606:617 arg1 applications 634:645 potential prophylactic or therapeutic applications 596:645 potential prophylactic or therapeutic applications 596:645 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 1 64 gly glycoproteins 296:308 arg1 glycoproteins 296:308 glycoproteins 296:308 glycoproteins in their capsid as infective virions 296:345 Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. 35312780 4 65 theme H5 870:871 arg1 cells 880:884 H5 insect cells 870:884 H5 insect cells 870:884 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 5 66 theme VP1 1032:1034 arg1 peptides 1036:1043 tryptic VP1 peptides 1024:1043 tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine 1024:1114 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 0 67 theme insect 65:70 arg1 cells 72:76 H5 insect cells 62:76 H5 insect cells 62:76 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 5 68 theme 70 1101:1102 arg1 % 1103:1103 % 1103:1103 % 1103:1103 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 6 69 theme liquid 1273:1278 arg1 spectrometry 1300:1311 liquid chromatography-mass spectrometry 1273:1311 liquid chromatography-mass spectrometry 1273:1311 Thr65, Ser67, and Thr350 were revealed by liquid chromatography-mass spectrometry to carry HexNAc or Hex-HexNAc modifications, respectively. 35312780 5 70 theme beta-elimination 1064:1079 arg1 addition 1089:1096 beta-elimination Michael addition 1064:1096 beta-elimination Michael addition in 70% ethylamine 1064:1114 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 1 71 gly glycosylated 237:248 arg1 proteins 198:205 surface proteins 190:205 surface proteins of most enveloped viruses 190:231 Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. 35312780 4 72 theme protruding 913:922 arg1 domains 924:930 the protruding domains 909:930 the protruding domains that are involved in receptor binding and immune reactivity 909:990 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 0 73 theme norovirus 12:20 arg1 GII.4 42:46 GII.4 42:46 GII.4 42:46 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 0 73 theme norovirus 12:20 arg1 VP1 37:39 Recombinant norovirus capsid protein VP1 0:39 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells 0:76 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 9 74 theme amino 1799:1803 arg1 chains 1815:1820 amino acid side chains 1799:1820 amino acid side chains involved in the binding of blood group active sugar receptors 1799:1882 Some modifications are located near amino acid side chains involved in the binding of blood group active sugar receptors. 35312780 5 75 theme modified 1221:1228 arg1 domain 1211:1216 the P2 domain 1204:1216 the P2 domain as modified 1204:1228 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 0 76 theme protein 29:35 arg1 GII.4 42:46 GII.4 42:46 GII.4 42:46 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 0 76 theme protein 29:35 arg1 VP1 37:39 Recombinant norovirus capsid protein VP1 0:39 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells 0:76 Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design. 35312780 7 77 dep confirmed 1436:1444 arg1 whereas 1485:1491 whereas 1485:1491 whereas 1485:1491 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 9 78 theme side 1810:1813 arg1 chains 1815:1820 amino acid side chains 1799:1820 amino acid side chains involved in the binding of blood group active sugar receptors 1799:1882 Some modifications are located near amino acid side chains involved in the binding of blood group active sugar receptors. 35312780 2 79 theme major 416:420 arg1 VP1 438:440 VP1 438:440 VP1 438:440 Noroviruses belong to the latter group and are known to express one major capsid protein (VP1) that lacks genuine glycosylation. 35312780 2 79 theme major 416:420 arg1 protein 429:435 one major capsid protein 412:435 one major capsid protein (VP1) that lacks genuine glycosylation 412:474 Noroviruses belong to the latter group and are known to express one major capsid protein (VP1) that lacks genuine glycosylation. 35312780 5 80 theme P1 1151:1152 arg1 domain 1154:1159 the P1 domain 1147:1159 the P1 domain 1147:1159 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 4 81 dep VLPs 805:808 arg1 Sydney 817:822 Sydney 817:822 Sydney 817:822 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 2 82 theme genuine 454:460 arg1 glycosylation 462:474 genuine glycosylation 454:474 genuine glycosylation 454:474 Noroviruses belong to the latter group and are known to express one major capsid protein (VP1) that lacks genuine glycosylation. 35312780 3 83 theme therapeutic 622:632 arg1 applications 634:645 potential prophylactic or therapeutic applications 596:645 potential prophylactic or therapeutic applications 596:645 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 4 84 theme recombinant 793:803 arg1 VLPs 805:808 recombinant VLPs 793:808 recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells 793:884 We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. 35312780 5 85 theme Mass 993:996 arg1 analysis 1012:1019 Mass spectrometric analysis 993:1019 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine 993:1114 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 3 86 theme reports 671:677 arg1 number 661:666 an increasing number 647:666 an increasing number of reports 647:677 In the context of vaccine development based on virus-like particles (VLPs) and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of VLPs that were produced as secretory products in insect cells. 35312780 1 87 theme infective 329:337 arg1 virions 339:345 infective virions 329:345 infective virions 329:345 Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. 35312780 7 88 theme VLP 1472:1474 arg1 protein 1476:1482 VLP protein 1472:1482 VLP protein 1472:1482 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 5 89 from addition 1089:1096 arg1 ethylamine 1105:1114 70% ethylamine 1101:1114 70% ethylamine 1101:1114 Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. 35312780 7 90 theme GlcNAc 1462:1467 arg1 presence 1450:1457 the presence 1446:1457 the presence of GlcNAc on VLP protein 1446:1482 Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. 35312780 9 91 theme group 1855:1859 arg1 receptors 1874:1882 blood group active sugar receptors 1849:1882 blood group active sugar receptors 1849:1882 Some modifications are located near amino acid side chains involved in the binding of blood group active sugar receptors. 35312780 8 92 theme Post-translational 1579:1596 arg1 modifications 1598:1610 Post-translational modifications 1579:1610 Post-translational modifications of virus capsid proteins 1579:1635 Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. 35312780 2 93 theme latter 374:379 arg1 group 381:385 the latter group 370:385 the latter group 370:385 Noroviruses belong to the latter group and are known to express one major capsid protein (VP1) that lacks genuine glycosylation. 37398095 8 0 theme root 1241:1244 arg1 density 1251:1257 increased root hair density 1231:1257 increased root hair density 1231:1257 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 7 1 theme inhibitory 1050:1059 arg1 activities 1061:1070 stronger inhibitory activities 1041:1070 stronger inhibitory activities 1041:1070 Docking analysis identified additional SOFTI analogs that showed stronger inhibitory activities. 37398095 2 2 theme O-linked 394:401 arg1 N-acetylglucosamine 403:421 O-linked N-acetylglucosamine 394:421 O-linked N-acetylglucosamine 394:421 In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. 37398095 5 3 theme GDP-fucose-binding 792:809 arg1 pocket 811:816 the GDP-fucose-binding pocket 788:816 the GDP-fucose-binding pocket of SPY 788:823 Computational analyses predicted that SOFTI binds to the GDP-fucose-binding pocket of SPY and competitively inhibits GDP-fucose binding. 37398095 6 4 theme O-fucosyltransferase 945:964 arg1 activity 966:973 its O-fucosyltransferase activity 941:973 its O-fucosyltransferase activity 941:973 In vitro assays confirmed that SOFTI interacts with SPY and inhibits its O-fucosyltransferase activity. 37398095 8 5 theme seedlings 1104:1112 arg1 treatment 1079:1087 SOFTI treatment 1073:1087 SOFTI treatment of Arabidopsis seedlings 1073:1112 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 3 6 from lethality 539:547 arg1 Arabidopsis 552:562 Arabidopsis 552:562 Arabidopsis 552:562 SPY and SEC play overlapping roles in cellular regulation and loss of both SPY and SEC causes embryo lethality in Arabidopsis. 37398095 1 7 theme cellular 204:211 arg1 homeostasis 213:223 cellular homeostasis 204:223 cellular homeostasis 204:223 Protein O-glycosylation is a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species. 37398095 11 8 theme agricultural 1603:1614 arg1 management 1616:1625 agricultural management 1603:1625 agricultural management 1603:1625 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 7 9 theme additional 1004:1013 arg1 analogs 1021:1027 additional SOFTI analogs 1004:1027 additional SOFTI analogs that showed stronger inhibitory activities 1004:1070 Docking analysis identified additional SOFTI analogs that showed stronger inhibitory activities. 37398095 7 10 theme SOFTI 1015:1019 arg1 analogs 1021:1027 additional SOFTI analogs 1004:1027 additional SOFTI analogs that showed stronger inhibitory activities 1004:1070 Docking analysis identified additional SOFTI analogs that showed stronger inhibitory activities. 37398095 2 11 theme posttranslational 308:324 arg1 modifications 326:338 posttranslational modifications 308:338 posttranslational modifications of hundreds of intracellular proteins 308:376 In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. 37398095 8 12 theme hair 1246:1249 arg1 density 1251:1257 increased root hair density 1231:1257 increased root hair density 1231:1257 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 2 13 link O-linked 394:401 arg1 N-acetylglucosamine 403:421 O-linked N-acetylglucosamine 394:421 O-linked N-acetylglucosamine 394:421 In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. 37398095 8 14 theme protein 1124:1130 arg1 O-fucosylation 1132:1145 protein O-fucosylation 1124:1145 protein O-fucosylation 1124:1145 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 2 15 theme intracellular 355:367 arg1 proteins 369:376 intracellular proteins 355:376 intracellular proteins 355:376 In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. 37398095 11 16 theme chemical 1528:1535 arg1 tool 1537:1540 a useful chemical tool 1519:1540 a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management 1519:1625 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 3 17 theme SEC 521:523 arg1 loss 500:503 loss 500:503 loss of both SPY and SEC 500:523 SPY and SEC play overlapping roles in cellular regulation and loss of both SPY and SEC causes embryo lethality in Arabidopsis. 37398095 11 18 theme SPY 1480:1482 arg1 SOFTI 1460:1464 SOFTI 1460:1464 SOFTI 1460:1464 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 11 18 theme SPY 1480:1482 arg1 inhibitor 1505:1513 a specific SPY O-fucosyltransferase inhibitor 1469:1513 a specific SPY O-fucosyltransferase inhibitor 1469:1513 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 8 19 theme SOFTI 1073:1077 arg1 treatment 1079:1087 SOFTI treatment 1073:1087 SOFTI treatment of Arabidopsis seedlings 1073:1112 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 4 20 theme f 695:695 arg1 nhibitor 717:724 f ucosyltransferase i nhibitor 695:724 a S PY O - f ucosyltransferase i nhibitor (SOFTI) 684:732 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 4 20 theme f 695:695 arg1 SOFTI 727:731 SOFTI 727:731 SOFTI 727:731 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 11 21 theme O-fucosyltransferase 1484:1503 arg1 SOFTI 1460:1464 SOFTI 1460:1464 SOFTI 1460:1464 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 11 21 theme O-fucosyltransferase 1484:1503 arg1 inhibitor 1505:1513 a specific SPY O-fucosyltransferase inhibitor 1469:1513 a specific SPY O-fucosyltransferase inhibitor 1469:1513 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 0 22 theme molecule 51:58 arg1 inhibitors 60:69 small molecule inhibitors 45:69 small molecule inhibitors of O-fucosyltransferase 45:93 Structure-based virtual screening identifies small molecule inhibitors of O-fucosyltransferase SPINDLY. 37398095 1 23 theme Protein 104:110 arg1 mechanism 152:160 a nutrient-signaling mechanism 131:160 a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species 131:248 Protein O-glycosylation is a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species. 37398095 1 23 theme Protein 104:110 arg1 O-glycosylation 112:126 Protein O-glycosylation 104:126 Protein O-glycosylation 104:126 Protein O-glycosylation is a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species. 37398095 4 24 theme PY 688:689 arg1 O 691:691 a S PY O 684:691 a S PY O - f ucosyltransferase i nhibitor (SOFTI) 684:732 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 0 25 theme virtual 16:22 arg1 screening 24:32 Structure-based virtual screening 0:32 Structure-based virtual screening 0:32 Structure-based virtual screening identifies small molecule inhibitors of O-fucosyltransferase SPINDLY. 37398095 8 26 theme increased 1231:1239 arg1 density 1251:1257 increased root hair density 1231:1257 increased root hair density 1231:1257 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 8 27 theme Arabidopsis 1092:1102 arg1 seedlings 1104:1112 Arabidopsis seedlings 1092:1112 Arabidopsis seedlings 1092:1112 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 6 28 dep In 872:873 arg1 vitro 875:879 vitro 875:879 vitro 875:879 In vitro assays confirmed that SOFTI interacts with SPY and inhibits its O-fucosyltransferase activity. 37398095 11 29 theme useful 1521:1526 arg1 tool 1537:1540 a useful chemical tool 1519:1540 a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management 1519:1625 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 1 30 theme different 232:240 arg1 species 242:248 different species 232:248 different species 232:248 Protein O-glycosylation is a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species. 37398095 0 31 theme Structure-based 0:14 arg1 screening 24:32 Structure-based virtual screening 0:32 Structure-based virtual screening 0:32 Structure-based virtual screening identifies small molecule inhibitors of O-fucosyltransferase SPINDLY. 37398095 4 32 theme chemical 608:615 arg1 libraries 617:625 chemical libraries 608:625 chemical libraries followed by in vitro and in planta assays 608:667 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 11 33 theme specific 1471:1478 arg1 SOFTI 1460:1464 SOFTI 1460:1464 SOFTI 1460:1464 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 11 33 theme specific 1471:1478 arg1 inhibitor 1505:1513 a specific SPY O-fucosyltransferase inhibitor 1469:1513 a specific SPY O-fucosyltransferase inhibitor 1469:1513 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 7 34 theme Docking 976:982 arg1 analysis 984:991 Docking analysis 976:991 Docking analysis 976:991 Docking analysis identified additional SOFTI analogs that showed stronger inhibitory activities. 37398095 2 35 theme hundreds 343:350 arg1 modifications 326:338 posttranslational modifications 308:338 posttranslational modifications of hundreds of intracellular proteins 308:376 In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. 37398095 3 36 theme cellular 476:483 arg1 regulation 485:494 cellular regulation 476:494 cellular regulation 476:494 SPY and SEC play overlapping roles in cellular regulation and loss of both SPY and SEC causes embryo lethality in Arabidopsis. 37398095 5 37 theme GDP-fucose 852:861 arg1 binding 863:869 GDP-fucose binding 852:869 GDP-fucose binding 852:869 Computational analyses predicted that SOFTI binds to the GDP-fucose-binding pocket of SPY and competitively inhibits GDP-fucose binding. 37398095 4 38 dep O 691:691 arg1 nhibitor 717:724 f ucosyltransferase i nhibitor 695:724 a S PY O - f ucosyltransferase i nhibitor (SOFTI) 684:732 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 4 38 dep O 691:691 arg1 SOFTI 727:731 SOFTI 727:731 SOFTI 727:731 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 10 39 theme sugar-dependent 1385:1399 arg1 growth 1401:1406 sugar-dependent growth 1385:1406 sugar-dependent growth of tomato seedlings 1385:1426 Similarly, SOFTI inhibited sugar-dependent growth of tomato seedlings. 37398095 8 40 theme sugar-dependent 1274:1288 arg1 growth 1290:1295 sugar-dependent growth 1274:1295 sugar-dependent growth 1274:1295 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 9 41 theme visible 1324:1330 arg1 effect 1332:1337 no visible effect 1321:1337 no visible effect 1321:1337 By contrast, SOFTI had no visible effect on the spy mutant. 37398095 1 42 theme nutrient-signaling 133:150 arg1 mechanism 152:160 a nutrient-signaling mechanism 131:160 a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species 131:248 Protein O-glycosylation is a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species. 37398095 1 42 theme nutrient-signaling 133:150 arg1 O-glycosylation 112:126 Protein O-glycosylation 104:126 Protein O-glycosylation 104:126 Protein O-glycosylation is a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species. 37398095 3 43 theme SPY 513:515 arg1 loss 500:503 loss 500:503 loss of both SPY and SEC 500:523 SPY and SEC play overlapping roles in cellular regulation and loss of both SPY and SEC causes embryo lethality in Arabidopsis. 37398095 3 44 theme overlapping 455:465 arg1 roles 467:471 overlapping roles 455:471 overlapping roles 455:471 SPY and SEC play overlapping roles in cellular regulation and loss of both SPY and SEC causes embryo lethality in Arabidopsis. 37398095 4 45 theme libraries 617:625 arg1 screening 595:603 structure-based virtual screening 571:603 structure-based virtual screening of chemical libraries followed by in vitro and in planta assays 571:667 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 11 46 theme functional 1546:1555 arg1 studies 1557:1563 functional studies 1546:1563 functional studies of O-fucosylation 1546:1581 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 4 47 theme S 686:686 arg1 O 691:691 a S PY O 684:691 a S PY O - f ucosyltransferase i nhibitor (SOFTI) 684:732 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 0 48 theme small 45:49 arg1 inhibitors 60:69 small molecule inhibitors 45:69 small molecule inhibitors of O-fucosyltransferase 45:93 Structure-based virtual screening identifies small molecule inhibitors of O-fucosyltransferase SPINDLY. 37398095 4 49 theme structure-based 571:585 arg1 screening 595:603 structure-based virtual screening 571:603 structure-based virtual screening of chemical libraries followed by in vitro and in planta assays 571:667 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 5 50 theme Computational 735:747 arg1 analyses 749:756 Computational analyses 735:756 Computational analyses 735:756 Computational analyses predicted that SOFTI binds to the GDP-fucose-binding pocket of SPY and competitively inhibits GDP-fucose binding. 37398095 5 51 theme SPY 821:823 arg1 pocket 811:816 the GDP-fucose-binding pocket 788:816 the GDP-fucose-binding pocket of SPY 788:823 Computational analyses predicted that SOFTI binds to the GDP-fucose-binding pocket of SPY and competitively inhibits GDP-fucose binding. 37398095 8 52 from germination 1218:1228 arg1 growth 1290:1295 sugar-dependent growth 1274:1295 sugar-dependent growth 1274:1295 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 10 53 theme seedlings 1418:1426 arg1 growth 1401:1406 sugar-dependent growth 1385:1406 sugar-dependent growth of tomato seedlings 1385:1426 Similarly, SOFTI inhibited sugar-dependent growth of tomato seedlings. 37398095 8 54 theme spy 1184:1186 arg1 mutants 1188:1194 the spy mutants 1180:1194 the spy mutants 1180:1194 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 10 55 theme tomato 1411:1416 arg1 seedlings 1418:1426 tomato seedlings 1411:1426 tomato seedlings 1411:1426 Similarly, SOFTI inhibited sugar-dependent growth of tomato seedlings. 37398095 3 56 theme embryo 532:537 arg1 lethality 539:547 embryo lethality 532:547 embryo lethality in Arabidopsis 532:562 SPY and SEC play overlapping roles in cellular regulation and loss of both SPY and SEC causes embryo lethality in Arabidopsis. 37398095 4 57 theme virtual 587:593 arg1 screening 595:603 structure-based virtual screening 571:603 structure-based virtual screening of chemical libraries followed by in vitro and in planta assays 571:667 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 8 58 theme seed 1213:1216 arg1 germination 1218:1228 early seed germination 1207:1228 early seed germination 1207:1228 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 2 59 theme proteins 369:376 arg1 hundreds 343:350 hundreds 343:350 hundreds of intracellular proteins 343:376 In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. 37398095 8 60 theme early 1207:1211 arg1 germination 1218:1228 early seed germination 1207:1228 early seed germination 1207:1228 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 6 61 theme In 872:873 arg1 assays 881:886 In vitro assays 872:886 In vitro assays 872:886 In vitro assays confirmed that SOFTI interacts with SPY and inhibits its O-fucosyltransferase activity. 37398095 1 62 theme essential 173:181 arg1 roles 183:187 essential roles 173:187 essential roles 173:187 Protein O-glycosylation is a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species. 37398095 9 63 contain had 1317:1319 arg1 SOFTI 1311:1315 SOFTI 1311:1315 SOFTI 1311:1315 By contrast, SOFTI had no visible effect on the spy mutant. 37398095 9 63 contain had 1317:1319 arg2 effect 1332:1337 no visible effect 1321:1337 no visible effect 1321:1337 By contrast, SOFTI had no visible effect on the spy mutant. 37398095 11 64 theme O-fucosylation 1568:1581 arg1 studies 1557:1563 functional studies 1546:1563 functional studies of O-fucosylation 1546:1581 These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management. 37398095 9 65 theme spy 1346:1348 arg1 mutant 1350:1355 the spy mutant 1342:1355 the spy mutant 1342:1355 By contrast, SOFTI had no visible effect on the spy mutant. 37398095 2 66 theme SECRET 280:285 arg1 SEC 294:296 SEC 294:296 SEC 294:296 In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. 37398095 2 66 theme SECRET 280:285 arg1 AGENT 287:291 SECRET AGENT 280:291 SECRET AGENT (SEC) 280:297 In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. 37398095 8 67 from density 1251:1257 arg1 growth 1290:1295 sugar-dependent growth 1274:1295 sugar-dependent growth 1274:1295 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 4 68 theme i 715:715 arg1 nhibitor 717:724 f ucosyltransferase i nhibitor 695:724 a S PY O - f ucosyltransferase i nhibitor (SOFTI) 684:732 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 4 68 theme i 715:715 arg1 SOFTI 727:731 SOFTI 727:731 SOFTI 727:731 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 8 69 from defect 1264:1269 arg1 growth 1290:1295 sugar-dependent growth 1274:1295 sugar-dependent growth 1274:1295 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 0 70 theme O-fucosyltransferase 74:93 arg1 inhibitors 60:69 small molecule inhibitors 45:69 small molecule inhibitors of O-fucosyltransferase 45:93 Structure-based virtual screening identifies small molecule inhibitors of O-fucosyltransferase SPINDLY. 37398095 8 71 theme similar 1169:1175 arg1 density 1251:1257 increased root hair density 1231:1257 increased root hair density 1231:1257 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 8 71 theme similar 1169:1175 arg1 germination 1218:1228 early seed germination 1207:1228 early seed germination 1207:1228 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 8 71 theme similar 1169:1175 arg1 phenotypes 1158:1167 phenotypes 1158:1167 phenotypes 1158:1167 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 8 71 theme similar 1169:1175 arg1 defect 1264:1269 defect 1264:1269 defect in sugar-dependent growth 1264:1295 SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. 37398095 7 72 theme stronger 1041:1048 arg1 activities 1061:1070 stronger inhibitory activities 1041:1070 stronger inhibitory activities 1041:1070 Docking analysis identified additional SOFTI analogs that showed stronger inhibitory activities. 37398095 4 73 theme ucosyltransferase 697:713 arg1 nhibitor 717:724 f ucosyltransferase i nhibitor 695:724 a S PY O - f ucosyltransferase i nhibitor (SOFTI) 684:732 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37398095 4 73 theme ucosyltransferase 697:713 arg1 SOFTI 727:731 SOFTI 727:731 SOFTI 727:731 Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a S PY O - f ucosyltransferase i nhibitor (SOFTI). 37014745 0 0 theme bioinformatics-assisted 97:119 arg1 selection 121:129 bioinformatics-assisted selection 97:129 bioinformatics-assisted selection of functional diversity 97:153 Substrate specificity and transglycosylation capacity of α-L-fucosidases across GH29 assessed by bioinformatics-assisted selection of functional diversity. 37014745 3 1 theme subfamily 535:543 arg1 division 545:552 no formal subfamily division 525:552 no formal subfamily division of GH29 α-L-fucosidases 525:576 There is no formal subfamily division of GH29 α-L-fucosidases, but they are nonetheless divided into two subfamilies: GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity. 37014745 7 2 theme CUPP 1479:1482 arg1 clusters 1484:1491 the same CUPP clusters 1470:1491 the same CUPP clusters 1470:1491 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 1 3 theme fucosylated 284:294 arg1 glycans 296:302 fucosylated glycans 284:302 fucosylated glycans 284:302 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 1 3 theme fucosylated 284:294 arg1 N- 315:316 N- 315:316 N- 315:316 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 1 3 theme fucosylated 284:294 arg1 glycans 331:337 O-linked glycans 322:337 O-linked glycans on proteins 322:349 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 9 4 theme CUPP 1718:1721 arg1 groups 1723:1728 CUPP groups 1718:1728 CUPP groups 1718:1728 In contrast, the transglycosylation capacity of GH29 α-L-fucosidases was distributed across a range of CUPP groups. 37014745 6 5 theme enzymatic 1190:1198 arg1 rates 1200:1204 different enzymatic rates 1180:1204 different enzymatic rates 1180:1204 The 21 enzymes exhibited different enzymatic rates on 8 test-substrates, CNP-Fuc, 2'FL, 3FL, Lewisa, Lewisx, Fuc-α1,6-GlcNAc, Fuc-α1,3-GlcNAc, and Fuc-α1,4-GlcNAc. 37014745 5 6 theme substrate 1026:1034 arg1 specificity 1036:1046 substrate specificity 1026:1046 substrate specificity 1026:1046 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 8 7 from general 1497:1503 arg1 useful 1515:1520 useful 1515:1520 useful 1515:1520 In general, CUPP was useful for resolving GH29 into functional diversity subgroups when considering hydrolytic activity. 37014745 1 8 theme important 391:399 arg1 roles 401:405 important roles 391:405 important roles 391:405 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 4 9 theme transglycosylation 802:819 arg1 ability 821:827 transglycosylation ability 802:827 transglycosylation ability 802:827 However, the sequence traits that determine substrate specificity and transglycosylation ability of GH29 enzymes are not well characterized. 37014745 3 10 dep is 522:523 arg1 GH29A 634:638 GH29A 634:638 GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity 634:729 There is no formal subfamily division of GH29 α-L-fucosidases, but they are nonetheless divided into two subfamilies: GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity. 37014745 0 11 theme diversity 145:153 arg1 selection 121:129 bioinformatics-assisted selection 97:129 bioinformatics-assisted selection of functional diversity 97:153 Substrate specificity and transglycosylation capacity of α-L-fucosidases across GH29 assessed by bioinformatics-assisted selection of functional diversity. 37014745 5 12 theme peptide-motif 943:955 arg1 clustering 957:966 peptide-motif clustering 943:966 peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns) 943:1011 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 3 13 theme α-L-fucosidases 562:576 arg1 division 545:552 no formal subfamily division 525:552 no formal subfamily division of GH29 α-L-fucosidases 525:576 There is no formal subfamily division of GH29 α-L-fucosidases, but they are nonetheless divided into two subfamilies: GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity. 37014745 7 14 theme enzymes 1377:1383 arg1 type 1369:1372 a particular type 1356:1372 a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters 1356:1491 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 5 15 theme functional 896:905 arg1 map 907:909 a new functional map 890:909 a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns) 890:1011 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 0 16 theme functional 134:143 arg1 diversity 145:153 functional diversity 134:153 functional diversity 134:153 Substrate specificity and transglycosylation capacity of α-L-fucosidases across GH29 assessed by bioinformatics-assisted selection of functional diversity. 37014745 8 17 theme functional 1546:1555 arg1 subgroups 1567:1575 functional diversity subgroups 1546:1575 functional diversity subgroups 1546:1575 In general, CUPP was useful for resolving GH29 into functional diversity subgroups when considering hydrolytic activity. 37014745 1 18 from glycans 331:337 arg1 proteins 342:349 proteins 342:349 proteins 342:349 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 8 19 from useful 1515:1520 arg1 general 1497:1503 general 1497:1503 general 1497:1503 In general, CUPP was useful for resolving GH29 into functional diversity subgroups when considering hydrolytic activity. 37014745 8 20 theme diversity 1557:1565 arg1 subgroups 1567:1575 functional diversity subgroups 1546:1575 functional diversity subgroups 1546:1575 In general, CUPP was useful for resolving GH29 into functional diversity subgroups when considering hydrolytic activity. 37014745 7 21 theme same 1474:1477 arg1 clusters 1484:1491 the same CUPP clusters 1470:1491 the same CUPP clusters 1470:1491 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 1 22 from N- 315:316 arg1 proteins 342:349 proteins 342:349 proteins 342:349 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 1 23 gly fucosylated 284:294 arg1 glycans 296:302 fucosylated glycans 284:302 fucosylated glycans 284:302 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 1 23 gly fucosylated 284:294 arg1 N- 315:316 N- 315:316 N- 315:316 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 1 23 gly fucosylated 284:294 arg1 glycans 331:337 O-linked glycans 322:337 O-linked glycans on proteins 322:349 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 4 24 theme substrate 776:784 arg1 specificity 786:796 substrate specificity 776:796 substrate specificity 776:796 However, the sequence traits that determine substrate specificity and transglycosylation ability of GH29 enzymes are not well characterized. 37014745 2 25 theme GH29 419:422 arg1 enzymes 424:430 GH29 enzymes 419:430 GH29 enzymes 419:430 GH29 enzymes work via a retaining exo-action mechanism, and some can catalyze transfucosylation. 37014745 0 26 theme Substrate 0:8 arg1 specificity 10:20 Substrate specificity 0:20 Substrate specificity 0:20 Substrate specificity and transglycosylation capacity of α-L-fucosidases across GH29 assessed by bioinformatics-assisted selection of functional diversity. 37014745 9 27 theme groups 1723:1728 arg1 range 1709:1713 a range 1707:1713 a range of CUPP groups 1707:1728 In contrast, the transglycosylation capacity of GH29 α-L-fucosidases was distributed across a range of CUPP groups. 37014745 5 28 theme representative 1086:1099 arg1 α-L-fucosidases 1101:1115 21 representative α-L-fucosidases 1083:1115 21 representative α-L-fucosidases 1083:1115 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 3 29 dep GH29A 634:638 arg1 having 693:698 having 693:698 GH29B having narrower substrate specificity 687:729 There is no formal subfamily division of GH29 α-L-fucosidases, but they are nonetheless divided into two subfamilies: GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity. 37014745 3 29 dep GH29A 634:638 arg1 having 640:645 having 640:645 having a range of substrate specificities 640:680 There is no formal subfamily division of GH29 α-L-fucosidases, but they are nonetheless divided into two subfamilies: GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity. 37014745 0 30 theme transglycosylation 26:43 arg1 capacity 45:52 transglycosylation capacity 26:52 transglycosylation capacity 26:52 Substrate specificity and transglycosylation capacity of α-L-fucosidases across GH29 assessed by bioinformatics-assisted selection of functional diversity. 37014745 7 31 contain having 1419:1424 arg2 activity 1426:1433 activity 1426:1433 activity on Lewisa or Lewisx categorized in the same CUPP clusters 1426:1491 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 7 31 contain having 1419:1424 arg1 enzymes 1411:1417 the enzymes 1407:1417 the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters 1407:1491 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 9 32 theme transglycosylation 1632:1649 arg1 capacity 1651:1658 the transglycosylation capacity 1628:1658 the transglycosylation capacity of GH29 α-L-fucosidases 1628:1682 In contrast, the transglycosylation capacity of GH29 α-L-fucosidases was distributed across a range of CUPP groups. 37014745 5 33 theme Unique 988:993 arg1 Patterns 1003:1010 Conserved Unique Peptide Patterns 978:1010 Conserved Unique Peptide Patterns 978:1010 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 5 33 theme Unique 988:993 arg1 CUPP 972:975 CUPP 972:975 CUPP (Conserved Unique Peptide Patterns) 972:1011 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 2 34 theme exo-action 453:462 arg1 mechanism 464:472 a retaining exo-action mechanism 441:472 a retaining exo-action mechanism 441:472 GH29 enzymes work via a retaining exo-action mechanism, and some can catalyze transfucosylation. 37014745 5 35 theme Conserved 978:986 arg1 Patterns 1003:1010 Conserved Unique Peptide Patterns 978:1010 Conserved Unique Peptide Patterns 978:1010 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 5 35 theme Conserved 978:986 arg1 CUPP 972:975 CUPP 972:975 CUPP (Conserved Unique Peptide Patterns) 972:1011 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 1 36 theme O-linked 322:329 arg1 glycans 331:337 O-linked glycans 322:337 O-linked glycans on proteins 322:349 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 4 37 theme GH29 832:835 arg1 enzymes 837:843 GH29 enzymes 832:843 GH29 enzymes 832:843 However, the sequence traits that determine substrate specificity and transglycosylation ability of GH29 enzymes are not well characterized. 37014745 5 38 theme Peptide 995:1001 arg1 Patterns 1003:1010 Conserved Unique Peptide Patterns 978:1010 Conserved Unique Peptide Patterns 978:1010 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 5 38 theme Peptide 995:1001 arg1 CUPP 972:975 CUPP 972:975 CUPP (Conserved Unique Peptide Patterns) 972:1011 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 2 39 theme retaining 443:451 arg1 mechanism 464:472 a retaining exo-action mechanism 441:472 a retaining exo-action mechanism 441:472 GH29 enzymes work via a retaining exo-action mechanism, and some can catalyze transfucosylation. 37014745 3 40 theme formal 528:533 arg1 division 545:552 no formal subfamily division 525:552 no formal subfamily division of GH29 α-L-fucosidases 525:576 There is no formal subfamily division of GH29 α-L-fucosidases, but they are nonetheless divided into two subfamilies: GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity. 37014745 5 41 theme CUPP 1131:1134 arg1 groups 1136:1141 the 53 CUPP groups 1124:1141 the 53 CUPP groups identified 1124:1152 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 5 42 theme transglycosylation 1052:1069 arg1 activity 1071:1078 transglycosylation activity 1052:1078 transglycosylation activity 1052:1078 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 5 43 theme family 914:919 arg1 members 926:932 family GH29 members 914:932 family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns) 914:1011 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 7 44 theme CUPP 1327:1330 arg1 groups 1332:1337 Certain CUPP groups 1319:1337 Certain CUPP groups 1319:1337 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 7 45 dep majority 1395:1402 arg1 e.g. 1386:1389 e.g. 1386:1389 e.g. 1386:1389 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 1 46 from glycans 296:302 arg1 release 261:267 hydrolytic release 250:267 hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins 250:349 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 3 47 theme substrate 658:666 arg1 specificities 668:680 substrate specificities 658:680 substrate specificities 658:680 There is no formal subfamily division of GH29 α-L-fucosidases, but they are nonetheless divided into two subfamilies: GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity. 37014745 7 48 theme enzymes 1411:1417 arg1 majority 1395:1402 the majority 1391:1402 the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters 1391:1491 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 9 49 theme GH29 1663:1666 arg1 α-L-fucosidases 1668:1682 GH29 α-L-fucosidases 1663:1682 GH29 α-L-fucosidases 1663:1682 In contrast, the transglycosylation capacity of GH29 α-L-fucosidases was distributed across a range of CUPP groups. 37014745 1 50 theme hydrolytic 250:259 arg1 release 261:267 hydrolytic release 250:267 hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins 250:349 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 8 51 theme hydrolytic 1594:1603 arg1 activity 1605:1612 hydrolytic activity 1594:1612 hydrolytic activity 1594:1612 In general, CUPP was useful for resolving GH29 into functional diversity subgroups when considering hydrolytic activity. 37014745 3 52 theme specificities 668:680 arg1 range 649:653 a range 647:653 a range of substrate specificities 647:680 There is no formal subfamily division of GH29 α-L-fucosidases, but they are nonetheless divided into two subfamilies: GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity. 37014745 4 53 theme sequence 745:752 arg1 traits 754:759 the sequence traits 741:759 the sequence traits that determine substrate specificity and transglycosylation ability of GH29 enzymes 741:843 However, the sequence traits that determine substrate specificity and transglycosylation ability of GH29 enzymes are not well characterized. 37014745 0 54 theme α-L-fucosidases 57:71 arg1 specificity 10:20 Substrate specificity 0:20 Substrate specificity 0:20 Substrate specificity and transglycosylation capacity of α-L-fucosidases across GH29 assessed by bioinformatics-assisted selection of functional diversity. 37014745 0 54 theme α-L-fucosidases 57:71 arg1 capacity 45:52 transglycosylation capacity 26:52 transglycosylation capacity 26:52 Substrate specificity and transglycosylation capacity of α-L-fucosidases across GH29 assessed by bioinformatics-assisted selection of functional diversity. 37014745 7 55 theme particular 1358:1367 arg1 type 1369:1372 a particular type 1356:1372 a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters 1356:1491 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 3 56 theme narrower 700:707 arg1 specificity 719:729 narrower substrate specificity 700:729 narrower substrate specificity 700:729 There is no formal subfamily division of GH29 α-L-fucosidases, but they are nonetheless divided into two subfamilies: GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity. 37014745 5 57 theme α-L-fucosidases 1101:1115 arg1 specificity 1036:1046 substrate specificity 1026:1046 substrate specificity 1026:1046 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 5 57 theme α-L-fucosidases 1101:1115 arg1 activity 1071:1078 transglycosylation activity 1052:1078 transglycosylation activity 1052:1078 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 1 58 theme Glycoside 156:164 arg1 family 176:181 Glycoside hydrolase family 29 156:184 Glycoside hydrolase family 29 (GH29) 156:191 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 1 58 theme Glycoside 156:164 arg1 GH29 187:190 GH29 187:190 GH29 187:190 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 9 59 theme α-L-fucosidases 1668:1682 arg1 capacity 1651:1658 the transglycosylation capacity 1628:1658 the transglycosylation capacity of GH29 α-L-fucosidases 1628:1682 In contrast, the transglycosylation capacity of GH29 α-L-fucosidases was distributed across a range of CUPP groups. 37014745 3 60 theme substrate 709:717 arg1 specificity 719:729 narrower substrate specificity 700:729 narrower substrate specificity 700:729 There is no formal subfamily division of GH29 α-L-fucosidases, but they are nonetheless divided into two subfamilies: GH29A having a range of substrate specificities, and GH29B having narrower substrate specificity. 37014745 10 61 theme sequence 1836:1843 arg1 comparison 1845:1854 sequence comparison 1836:1854 sequence comparison 1836:1854 Transglycosylation thus appears to be a common trait among these enzymes, and not readily predicted from sequence comparison. 37014745 1 62 theme hydrolase 166:174 arg1 family 176:181 Glycoside hydrolase family 29 156:184 Glycoside hydrolase family 29 (GH29) 156:191 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 1 62 theme hydrolase 166:174 arg1 GH29 187:190 GH29 187:190 GH29 187:190 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 7 63 from activity 1426:1433 arg1 Lewisx 1448:1453 Lewisx 1448:1453 Lewisx 1448:1453 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 7 63 from activity 1426:1433 arg1 Lewisa 1438:1443 Lewisa 1438:1443 Lewisa 1438:1443 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 10 64 theme common 1771:1776 arg1 trait 1778:1782 a common trait 1769:1782 a common trait among these enzymes 1769:1802 Transglycosylation thus appears to be a common trait among these enzymes, and not readily predicted from sequence comparison. 37014745 4 65 theme enzymes 837:843 arg1 specificity 786:796 substrate specificity 776:796 substrate specificity 776:796 However, the sequence traits that determine substrate specificity and transglycosylation ability of GH29 enzymes are not well characterized. 37014745 4 65 theme enzymes 837:843 arg1 ability 821:827 transglycosylation ability 802:827 transglycosylation ability 802:827 However, the sequence traits that determine substrate specificity and transglycosylation ability of GH29 enzymes are not well characterized. 37014745 1 66 link O-linked 322:329 arg1 glycans 331:337 O-linked glycans 322:337 O-linked glycans on proteins 322:349 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 6 67 theme different 1180:1188 arg1 rates 1200:1204 different enzymatic rates 1180:1204 different enzymatic rates 1180:1204 The 21 enzymes exhibited different enzymatic rates on 8 test-substrates, CNP-Fuc, 2'FL, 3FL, Lewisa, Lewisx, Fuc-α1,6-GlcNAc, Fuc-α1,3-GlcNAc, and Fuc-α1,4-GlcNAc. 37014745 5 68 theme new 892:894 arg1 map 907:909 a new functional map 890:909 a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns) 890:1011 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 1 69 dep enzymes 227:233 arg1 i.e. 222:225 i.e. 222:225 i.e. 222:225 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 5 70 theme GH29 921:924 arg1 members 926:932 family GH29 members 914:932 family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns) 914:1011 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 37014745 1 71 theme fucose 272:277 arg1 release 261:267 hydrolytic release 250:267 hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins 250:349 Glycoside hydrolase family 29 (GH29) encompasses α-L-fucosidases, i.e. enzymes which catalyze hydrolytic release of fucose from fucosylated glycans, including N- and O-linked glycans on proteins, and these α-L-fucosidases clearly play important roles in biology. 37014745 7 72 theme Certain 1319:1325 arg1 groups 1332:1337 Certain CUPP groups 1319:1337 Certain CUPP groups 1319:1337 Certain CUPP groups clearly harbored a particular type of enzymes, e.g. the majority of the enzymes having activity on Lewisa or Lewisx categorized in the same CUPP clusters. 37014745 5 73 theme members 926:932 arg1 map 907:909 a new functional map 890:909 a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns) 890:1011 Here, we present a new functional map of family GH29 members based on peptide-motif clustering via CUPP (Conserved Unique Peptide Patterns), and compare substrate specificity and transglycosylation activity of 21 representative α-L-fucosidases across the 53 CUPP groups identified. 36736606 0 0 theme partitioning 61:72 arg1 property 74:81 a low partitioning property 55:81 a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain 55:173 Evidence that only EWS among the FET proteins acquires a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain. 36736606 4 1 from nucleus 663:669 arg1 formation 713:721 the cellular granule formation 692:721 the cellular granule formation of FET proteins 692:737 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 4 1 from nucleus 663:669 arg1 translocation 640:652 the hyperosmotic stress-dependent translocation 606:652 the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm 606:686 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 6 2 theme EWS 1106:1108 arg1 LCD 1099:1101 the LCD 1095:1101 the LCD of EWS 1095:1108 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 0 3 theme low 57:59 arg1 property 74:81 a low partitioning property 55:81 a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain 55:173 Evidence that only EWS among the FET proteins acquires a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain. 36736606 9 4 from property 1506:1513 arg1 response 1534:1541 cellular stress response 1518:1541 cellular stress response 1518:1541 The glycosylation may play an essential role in regulating physiological functions of EWS, such as transcriptional activity, in addition to the property in cellular stress response. 36736606 6 5 theme residues 1028:1035 arg1 analysis 974:981 Chemoenzymatic labeling analysis 950:981 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues 950:1035 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 8 6 theme unique 1314:1319 arg1 property 1321:1328 the unique property 1310:1328 the unique property 1310:1328 These results suggest that among the FET proteins, only EWS has acquired the unique property through O-GlcNAc glycosylation. 36736606 4 7 from cytoplasm 811:819 arg1 likely 761:766 likely 761:766 likely 761:766 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 4 8 theme proteins 730:737 arg1 formation 713:721 the cellular granule formation 692:721 the cellular granule formation of FET proteins 692:737 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 4 8 theme proteins 730:737 arg1 translocation 640:652 the hyperosmotic stress-dependent translocation 606:652 the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm 606:686 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 4 9 theme hyperosmotic 610:621 arg1 translocation 640:652 the hyperosmotic stress-dependent translocation 606:652 the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm 606:686 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 1 10 theme common 219:224 arg1 organization 233:244 a common domain organization 217:244 a common domain organization 217:244 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 4 11 theme granule 705:711 arg1 formation 713:721 the cellular granule formation 692:721 the cellular granule formation of FET proteins 692:737 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 7 12 theme EWS 1167:1169 arg1 property 1197:1204 the less partitioning property 1175:1204 the less partitioning property under the hyperosmotic stress 1175:1234 A correlation was observed between the glycosylation of EWS and the less partitioning property under the hyperosmotic stress. 36736606 7 12 theme EWS 1167:1169 arg1 glycosylation 1150:1162 the glycosylation 1146:1162 the glycosylation of EWS 1146:1169 A correlation was observed between the glycosylation of EWS and the less partitioning property under the hyperosmotic stress. 36736606 7 13 theme partitioning 1184:1195 arg1 property 1197:1204 the less partitioning property 1175:1204 the less partitioning property under the hyperosmotic stress 1175:1234 A correlation was observed between the glycosylation of EWS and the less partitioning property under the hyperosmotic stress. 36736606 4 14 theme FET 726:728 arg1 proteins 730:737 FET proteins 726:737 FET proteins 726:737 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 0 15 from glycosylation 132:144 arg1 domain 168:173 its low-complexity domain 149:173 its low-complexity domain 149:173 Evidence that only EWS among the FET proteins acquires a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain. 36736606 0 16 theme hyperosmotic 91:102 arg1 response 111:118 the hyperosmotic stress response 87:118 the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain 87:173 Evidence that only EWS among the FET proteins acquires a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain. 36736606 9 17 theme physiological 1421:1433 arg1 activity 1477:1484 transcriptional activity 1461:1484 transcriptional activity 1461:1484 The glycosylation may play an essential role in regulating physiological functions of EWS, such as transcriptional activity, in addition to the property in cellular stress response. 36736606 9 17 theme physiological 1421:1433 arg1 functions 1435:1443 physiological functions 1421:1443 physiological functions 1421:1443 The glycosylation may play an essential role in regulating physiological functions of EWS, such as transcriptional activity, in addition to the property in cellular stress response. 36736606 7 18 gly glycosylation 1150:1162 arg1 EWS 1167:1169 EWS 1167:1169 EWS 1167:1169 A correlation was observed between the glycosylation of EWS and the less partitioning property under the hyperosmotic stress. 36736606 2 19 theme FET 350:352 arg1 proteins 354:361 the FET proteins 346:361 the FET proteins 346:361 Of the FET proteins, however, only EWS appears to have a distinct property in the cellular stress response. 36736606 1 20 theme domain 226:231 arg1 organization 233:244 a common domain organization 217:244 a common domain organization 217:244 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 1 21 theme gene 326:329 arg1 expression 331:340 gene expression 326:340 gene expression 326:340 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 4 22 theme cellular 786:793 arg1 granules 795:802 cellular granules 786:802 cellular granules 786:802 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 2 23 contain have 393:396 arg2 property 409:416 a distinct property 398:416 a distinct property 398:416 Of the FET proteins, however, only EWS appears to have a distinct property in the cellular stress response. 36736606 2 23 contain have 393:396 arg1 EWS 378:380 only EWS 373:380 only EWS 373:380 Of the FET proteins, however, only EWS appears to have a distinct property in the cellular stress response. 36736606 5 24 theme partitioning 872:883 arg1 property 885:892 the less partitioning property 863:892 the less partitioning property of EWS 863:899 The domain involved in the less partitioning property of EWS was found to be its low-complexity domain (LCD). 36736606 9 25 theme essential 1392:1400 arg1 role 1402:1405 an essential role 1389:1405 an essential role 1389:1405 The glycosylation may play an essential role in regulating physiological functions of EWS, such as transcriptional activity, in addition to the property in cellular stress response. 36736606 5 26 theme low-complexity 921:934 arg1 domain 936:941 its low-complexity domain 917:941 its low-complexity domain (LCD) 917:947 The domain involved in the less partitioning property of EWS was found to be its low-complexity domain (LCD). 36736606 5 26 theme low-complexity 921:934 arg1 domain 844:849 The domain 840:849 The domain involved in the less partitioning property of EWS 840:899 The domain involved in the less partitioning property of EWS was found to be its low-complexity domain (LCD). 36736606 5 26 theme low-complexity 921:934 arg1 LCD 944:946 LCD 944:946 LCD 944:946 The domain involved in the less partitioning property of EWS was found to be its low-complexity domain (LCD). 36736606 1 27 theme expression 331:340 arg1 regulation 312:321 the regulation 308:321 the regulation of gene expression 308:340 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 6 28 gly glycosylation 1060:1072 arg2 LCD 1099:1101 the LCD 1095:1101 the LCD of EWS 1095:1108 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 3 29 theme hyperosmotic 501:512 arg1 response 521:528 hyperosmotic stress response 501:528 hyperosmotic stress response 501:528 Therefore, we focused on the relationship between hyperosmotic stress response and post-translational modifications of the FET proteins. 36736606 1 30 theme FET 176:178 arg1 TAF15 204:208 TAF15 204:208 TAF15 204:208 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 1 30 theme FET 176:178 arg1 FUS 190:192 FUS 190:192 FUS 190:192 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 1 30 theme FET 176:178 arg1 proteins 180:187 FET proteins 176:187 FET proteins (FUS, EWS, and TAF15) 176:209 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 1 30 theme FET 176:178 arg1 EWS 195:197 EWS 195:197 EWS 195:197 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 3 31 theme stress 514:519 arg1 response 521:528 hyperosmotic stress response 501:528 hyperosmotic stress response 501:528 Therefore, we focused on the relationship between hyperosmotic stress response and post-translational modifications of the FET proteins. 36736606 4 32 theme stress-dependent 623:638 arg1 translocation 640:652 the hyperosmotic stress-dependent translocation 606:652 the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm 606:686 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 4 33 theme cellular 696:703 arg1 formation 713:721 the cellular granule formation 692:721 the cellular granule formation of FET proteins 692:737 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 8 34 theme FET 1274:1276 arg1 proteins 1278:1285 the FET proteins 1270:1285 the FET proteins 1270:1285 These results suggest that among the FET proteins, only EWS has acquired the unique property through O-GlcNAc glycosylation. 36736606 8 35 theme O-GlcNAc 1338:1345 arg1 glycosylation 1347:1359 O-GlcNAc glycosylation 1338:1359 O-GlcNAc glycosylation 1338:1359 These results suggest that among the FET proteins, only EWS has acquired the unique property through O-GlcNAc glycosylation. 36736606 6 36 theme O-linked 986:993 arg1 O-GlcNAc 1018:1025 O-GlcNAc 1018:1025 O-GlcNAc 1018:1025 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 6 36 theme O-linked 986:993 arg1 β-N-acetylglucosamine 995:1015 O-linked β-N-acetylglucosamine 986:1015 O-linked β-N-acetylglucosamine (O-GlcNAc) residues 986:1035 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 2 37 theme only 373:376 arg1 EWS 378:380 only EWS 373:380 only EWS 373:380 Of the FET proteins, however, only EWS appears to have a distinct property in the cellular stress response. 36736606 0 38 theme stress 104:109 arg1 response 111:118 the hyperosmotic stress response 87:118 the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain 87:173 Evidence that only EWS among the FET proteins acquires a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain. 36736606 5 39 theme EWS 897:899 arg1 property 885:892 the less partitioning property 863:892 the less partitioning property of EWS 863:899 The domain involved in the less partitioning property of EWS was found to be its low-complexity domain (LCD). 36736606 6 40 theme O-GlcNAc 1051:1058 arg1 glycosylation 1060:1072 O-GlcNAc glycosylation 1051:1072 O-GlcNAc glycosylation 1051:1072 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 9 41 dep property 1506:1513 arg1 addition 1490:1497 addition 1490:1497 addition 1490:1497 The glycosylation may play an essential role in regulating physiological functions of EWS, such as transcriptional activity, in addition to the property in cellular stress response. 36736606 0 42 theme O-GlcNAc 123:130 arg1 glycosylation 132:144 O-GlcNAc glycosylation 123:144 O-GlcNAc glycosylation on its low-complexity domain 123:173 Evidence that only EWS among the FET proteins acquires a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain. 36736606 3 43 theme post-translational 534:551 arg1 modifications 553:565 post-translational modifications 534:565 post-translational modifications of the FET proteins 534:585 Therefore, we focused on the relationship between hyperosmotic stress response and post-translational modifications of the FET proteins. 36736606 6 44 theme β-N-acetylglucosamine 995:1015 arg1 residues 1028:1035 O-linked β-N-acetylglucosamine (O-GlcNAc) residues 986:1035 O-linked β-N-acetylglucosamine (O-GlcNAc) residues 986:1035 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 2 45 theme distinct 400:407 arg1 property 409:416 a distinct property 398:416 a distinct property 398:416 Of the FET proteins, however, only EWS appears to have a distinct property in the cellular stress response. 36736606 1 46 dep proteins 180:187 arg1 TAF15 204:208 TAF15 204:208 TAF15 204:208 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 1 46 dep proteins 180:187 arg1 FUS 190:192 FUS 190:192 FUS 190:192 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 1 46 dep proteins 180:187 arg1 proteins 180:187 FET proteins 176:187 FET proteins (FUS, EWS, and TAF15) 176:209 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 1 46 dep proteins 180:187 arg1 EWS 195:197 EWS 195:197 EWS 195:197 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36736606 6 47 theme labeling 965:972 arg1 analysis 974:981 Chemoenzymatic labeling analysis 950:981 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues 950:1035 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 8 48 theme only 1288:1291 arg1 EWS 1293:1295 only EWS 1288:1295 only EWS 1288:1295 These results suggest that among the FET proteins, only EWS has acquired the unique property through O-GlcNAc glycosylation. 36736606 6 49 link O-linked 986:993 arg1 O-GlcNAc 1018:1025 O-GlcNAc 1018:1025 O-GlcNAc 1018:1025 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 6 49 link O-linked 986:993 arg1 β-N-acetylglucosamine 995:1015 O-linked β-N-acetylglucosamine 986:1015 O-linked β-N-acetylglucosamine (O-GlcNAc) residues 986:1035 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 9 50 theme EWS 1448:1450 arg1 activity 1477:1484 transcriptional activity 1461:1484 transcriptional activity 1461:1484 The glycosylation may play an essential role in regulating physiological functions of EWS, such as transcriptional activity, in addition to the property in cellular stress response. 36736606 9 50 theme EWS 1448:1450 arg1 functions 1435:1443 physiological functions 1421:1443 physiological functions 1421:1443 The glycosylation may play an essential role in regulating physiological functions of EWS, such as transcriptional activity, in addition to the property in cellular stress response. 36736606 0 51 theme FET 33:35 arg1 proteins 37:44 the FET proteins 29:44 the FET proteins 29:44 Evidence that only EWS among the FET proteins acquires a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain. 36736606 9 52 theme cellular 1518:1525 arg1 response 1534:1541 cellular stress response 1518:1541 cellular stress response 1518:1541 The glycosylation may play an essential role in regulating physiological functions of EWS, such as transcriptional activity, in addition to the property in cellular stress response. 36736606 0 53 theme low-complexity 153:166 arg1 domain 168:173 its low-complexity domain 149:173 its low-complexity domain 149:173 Evidence that only EWS among the FET proteins acquires a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain. 36736606 3 54 theme FET 574:576 arg1 proteins 578:585 the FET proteins 570:585 the FET proteins 570:585 Therefore, we focused on the relationship between hyperosmotic stress response and post-translational modifications of the FET proteins. 36736606 4 55 from likely 761:766 arg1 cytoplasm 811:819 the cytoplasm 807:819 the cytoplasm 807:819 We confirmed that the hyperosmotic stress-dependent translocation from the nucleus to the cytoplasm and the cellular granule formation of FET proteins, and that EWS is less likely to partition into cellular granules in the cytoplasm than FUS or TAF15. 36736606 9 56 theme stress 1527:1532 arg1 response 1534:1541 cellular stress response 1518:1541 cellular stress response 1518:1541 The glycosylation may play an essential role in regulating physiological functions of EWS, such as transcriptional activity, in addition to the property in cellular stress response. 36736606 6 57 theme Chemoenzymatic 950:963 arg1 labeling 965:972 Chemoenzymatic labeling 950:972 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues 950:1035 Chemoenzymatic labeling analysis of O-linked β-N-acetylglucosamine (O-GlcNAc) residues revealed that O-GlcNAc glycosylation occurs frequently in the LCD of EWS. 36736606 3 58 theme proteins 578:585 arg1 response 521:528 hyperosmotic stress response 501:528 hyperosmotic stress response 501:528 Therefore, we focused on the relationship between hyperosmotic stress response and post-translational modifications of the FET proteins. 36736606 3 58 theme proteins 578:585 arg1 modifications 553:565 post-translational modifications 534:565 post-translational modifications of the FET proteins 534:585 Therefore, we focused on the relationship between hyperosmotic stress response and post-translational modifications of the FET proteins. 36736606 7 59 theme hyperosmotic 1216:1227 arg1 stress 1229:1234 the hyperosmotic stress 1212:1234 the hyperosmotic stress 1212:1234 A correlation was observed between the glycosylation of EWS and the less partitioning property under the hyperosmotic stress. 36736606 2 60 theme stress 434:439 arg1 response 441:448 the cellular stress response 421:448 the cellular stress response 421:448 Of the FET proteins, however, only EWS appears to have a distinct property in the cellular stress response. 36736606 9 61 theme transcriptional 1461:1475 arg1 activity 1477:1484 transcriptional activity 1461:1484 transcriptional activity 1461:1484 The glycosylation may play an essential role in regulating physiological functions of EWS, such as transcriptional activity, in addition to the property in cellular stress response. 36736606 0 62 gly glycosylation 132:144 arg1 domain 168:173 its low-complexity domain 149:173 its low-complexity domain 149:173 Evidence that only EWS among the FET proteins acquires a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain. 36736606 2 63 theme cellular 425:432 arg1 response 441:448 the cellular stress response 421:448 the cellular stress response 421:448 Of the FET proteins, however, only EWS appears to have a distinct property in the cellular stress response. 36736606 1 64 theme multifunctional 283:297 arg1 roles 299:303 similarly multifunctional roles 273:303 similarly multifunctional roles 273:303 FET proteins (FUS, EWS, and TAF15) share a common domain organization, bind RNA/DNA, and perform similarly multifunctional roles in the regulation of gene expression. 36031959 3 0 theme nonulosonic 297:307 arg1 sugars 314:319 nonulosonic acid sugars 297:319 nonulosonic acid sugars such as pseudaminic acid 297:344 For bacteria that use nonulosonic acid sugars such as pseudaminic acid, this glycosylation process is essential for the formation of a functional flagellum. 36031959 3 0 theme nonulosonic 297:307 arg1 acid 341:344 pseudaminic acid 329:344 pseudaminic acid 329:344 For bacteria that use nonulosonic acid sugars such as pseudaminic acid, this glycosylation process is essential for the formation of a functional flagellum. 36031959 9 1 theme hydrophobic 1109:1119 arg1 acids 1127:1131 hydrophobic amino acids 1109:1131 hydrophobic amino acids 1109:1131 For flagellin O-linked glycosylation, there is no known consensus sequence, although hydrophobic amino acids have been suggested to play a role. 36031959 10 2 theme flagellin 1440:1448 arg1 process 1464:1470 the flagellin glycosylation process 1436:1470 the flagellin glycosylation process 1436:1470 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 3 theme present 1359:1365 arg1 flagellin 1349:1357 flagellin 1349:1357 flagellin 1349:1357 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 3 theme present 1359:1365 arg1 amount 1339:1344 the amount 1335:1344 the amount of flagellin present in the cells 1335:1378 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 3 4 theme acid 309:312 arg1 sugars 314:319 nonulosonic acid sugars 297:319 nonulosonic acid sugars such as pseudaminic acid 297:344 For bacteria that use nonulosonic acid sugars such as pseudaminic acid, this glycosylation process is essential for the formation of a functional flagellum. 36031959 3 4 theme acid 309:312 arg1 acid 341:344 pseudaminic acid 329:344 pseudaminic acid 329:344 For bacteria that use nonulosonic acid sugars such as pseudaminic acid, this glycosylation process is essential for the formation of a functional flagellum. 36031959 5 5 theme simple 562:567 arg1 system 583:588 a genetically simple glycosylation system 548:588 a genetically simple glycosylation system 548:588 Aeromonas caviae is a model for this process as it has a genetically simple glycosylation system. 36031959 8 6 theme Site-directed 847:859 arg1 mutagenesis 861:871 Site-directed mutagenesis 847:871 Site-directed mutagenesis of particular glycosylation sites in most cases 847:919 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 10 7 from reduction 1309:1317 arg1 motility 1322:1329 motility 1322:1329 motility 1322:1329 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 5 8 theme glycosylation 569:581 arg1 system 583:588 a genetically simple glycosylation system 548:588 a genetically simple glycosylation system 548:588 Aeromonas caviae is a model for this process as it has a genetically simple glycosylation system. 36031959 10 9 theme site-directed 1194:1206 arg1 mutagenesis 1208:1218 site-directed mutagenesis 1194:1218 site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation 1194:1288 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 6 10 dep A. 652:653 arg1 caviae 655:660 caviae 655:660 caviae 655:660 Here, we investigated the localization of the glycans on the A. caviae flagellum filament. 36031959 9 11 theme amino 1121:1125 arg1 acids 1127:1131 hydrophobic amino acids 1109:1131 hydrophobic amino acids 1109:1131 For flagellin O-linked glycosylation, there is no known consensus sequence, although hydrophobic amino acids have been suggested to play a role. 36031959 9 12 theme known 1074:1078 arg1 sequence 1090:1097 no known consensus sequence 1071:1097 no known consensus sequence 1071:1097 For flagellin O-linked glycosylation, there is no known consensus sequence, although hydrophobic amino acids have been suggested to play a role. 36031959 7 13 theme mass 688:691 arg1 spectrometry 693:704 mass spectrometry 688:704 mass spectrometry 688:704 Using mass spectrometry it was revealed that pseudaminic acid O-glycosylation was heterogeneous with no serine or threonine sites that were constantly glycosylated. 36031959 10 14 theme isoleucine 1223:1232 arg1 residues 1245:1252 isoleucine or leucine residues 1223:1252 isoleucine or leucine residues flanking the sites of glycosylation 1223:1288 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 4 15 theme specific 445:452 arg1 role 454:457 the specific role 441:457 the specific role of glycosylation 441:474 However, the specific role of glycosylation remains elusive. 36031959 7 16 with heterogeneous 764:776 arg1 sites 806:810 no serine or threonine sites 783:810 no serine or threonine sites that were constantly glycosylated 783:844 Using mass spectrometry it was revealed that pseudaminic acid O-glycosylation was heterogeneous with no serine or threonine sites that were constantly glycosylated. 36031959 1 17 theme Bacterial 79:87 arg1 swimming 89:96 Bacterial swimming 79:96 Bacterial swimming 79:96 Bacterial swimming is mediated by the rotation of a flagellar filament. 36031959 9 18 theme consensus 1080:1088 arg1 sequence 1090:1097 no known consensus sequence 1071:1097 no known consensus sequence 1071:1097 For flagellin O-linked glycosylation, there is no known consensus sequence, although hydrophobic amino acids have been suggested to play a role. 36031959 3 19 theme functional 410:419 arg1 flagellum 421:429 a functional flagellum 408:429 a functional flagellum 408:429 For bacteria that use nonulosonic acid sugars such as pseudaminic acid, this glycosylation process is essential for the formation of a functional flagellum. 36031959 3 20 theme pseudaminic 329:339 arg1 acid 341:344 pseudaminic acid 329:344 pseudaminic acid 329:344 For bacteria that use nonulosonic acid sugars such as pseudaminic acid, this glycosylation process is essential for the formation of a functional flagellum. 36031959 4 21 theme glycosylation 462:474 arg1 role 454:457 the specific role 441:457 the specific role of glycosylation 441:474 However, the specific role of glycosylation remains elusive. 36031959 8 22 theme Western 1009:1015 arg1 blots 1017:1021 Western blots 1009:1021 Western blots 1009:1021 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 6 23 theme flagellum 662:670 arg1 filament 672:679 the A. caviae flagellum filament 648:679 the A. caviae flagellum filament 648:679 Here, we investigated the localization of the glycans on the A. caviae flagellum filament. 36031959 3 24 theme flagellum 421:429 arg1 formation 395:403 the formation 391:403 the formation of a functional flagellum 391:429 For bacteria that use nonulosonic acid sugars such as pseudaminic acid, this glycosylation process is essential for the formation of a functional flagellum. 36031959 8 25 theme glycosylation 887:899 arg1 sites 901:905 particular glycosylation sites 876:905 particular glycosylation sites 876:905 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 10 26 theme hydrophobic 1409:1419 arg1 acids 1427:1431 these hydrophobic amino acids 1403:1431 these hydrophobic amino acids 1403:1431 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 2 27 theme Many 151:154 arg1 bacteria 156:163 Many bacteria 151:163 Many bacteria 151:163 Many bacteria are now known to be able to O-glycosylate their flagellins, the proteins that make up the flagellar filament. 36031959 0 28 theme Heterogeneous 0:12 arg1 glycosylation 14:26 Heterogeneous glycosylation 0:26 Heterogeneous glycosylation 0:26 Heterogeneous glycosylation and methylation of the Aeromonas caviae flagellin. 36031959 7 29 theme serine 786:791 arg1 sites 806:810 no serine or threonine sites 783:810 no serine or threonine sites that were constantly glycosylated 783:844 Using mass spectrometry it was revealed that pseudaminic acid O-glycosylation was heterogeneous with no serine or threonine sites that were constantly glycosylated. 36031959 10 30 theme glycosylation 1450:1462 arg1 process 1464:1470 the flagellin glycosylation process 1436:1470 the flagellin glycosylation process 1436:1470 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 6 31 theme A. 652:653 arg1 filament 672:679 the A. caviae flagellum filament 648:679 the A. caviae flagellum filament 648:679 Here, we investigated the localization of the glycans on the A. caviae flagellum filament. 36031959 8 32 theme detectable 985:994 arg1 flagellin 996:1004 less detectable flagellin 980:1004 less detectable flagellin 980:1004 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 8 33 theme sites 901:905 arg1 mutagenesis 861:871 Site-directed mutagenesis 847:871 Site-directed mutagenesis of particular glycosylation sites in most cases 847:919 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 3 34 theme glycosylation 352:364 arg1 process 366:372 this glycosylation process 347:372 this glycosylation process 347:372 For bacteria that use nonulosonic acid sugars such as pseudaminic acid, this glycosylation process is essential for the formation of a functional flagellum. 36031959 8 35 contain had 946:948 arg1 strains 933:939 strains 933:939 strains that had reduced motility and produced less detectable flagellin on Western blots 933:1021 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 8 35 contain had 946:948 arg2 motility 958:965 reduced motility 950:965 reduced motility 950:965 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 2 36 theme flagellar 255:263 arg1 filament 265:272 the flagellar filament 251:272 the flagellar filament 251:272 Many bacteria are now known to be able to O-glycosylate their flagellins, the proteins that make up the flagellar filament. 36031959 8 37 theme most 910:913 arg1 cases 915:919 most cases 910:919 most cases 910:919 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 7 38 theme threonine 796:804 arg1 sites 806:810 no serine or threonine sites 783:810 no serine or threonine sites that were constantly glycosylated 783:844 Using mass spectrometry it was revealed that pseudaminic acid O-glycosylation was heterogeneous with no serine or threonine sites that were constantly glycosylated. 36031959 8 39 theme particular 876:885 arg1 sites 901:905 particular glycosylation sites 876:905 particular glycosylation sites 876:905 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 10 40 from present 1359:1365 arg1 cells 1374:1378 the cells 1370:1378 the cells 1370:1378 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 7 41 dep revealed 713:720 arg1 Using 682:686 Using 682:686 Using mass spectrometry 682:704 Using mass spectrometry it was revealed that pseudaminic acid O-glycosylation was heterogeneous with no serine or threonine sites that were constantly glycosylated. 36031959 6 42 from localization 617:628 arg1 filament 672:679 the A. caviae flagellum filament 648:679 the A. caviae flagellum filament 648:679 Here, we investigated the localization of the glycans on the A. caviae flagellum filament. 36031959 6 43 theme glycans 637:643 arg1 localization 617:628 the localization 613:628 the localization of the glycans on the A. caviae flagellum filament 613:679 Here, we investigated the localization of the glycans on the A. caviae flagellum filament. 36031959 5 44 contain has 544:546 arg1 it 541:542 it 541:542 it 541:542 Aeromonas caviae is a model for this process as it has a genetically simple glycosylation system. 36031959 5 44 contain has 544:546 arg2 system 583:588 a genetically simple glycosylation system 548:588 a genetically simple glycosylation system 548:588 Aeromonas caviae is a model for this process as it has a genetically simple glycosylation system. 36031959 10 45 from amount 1339:1344 arg1 motility 1322:1329 motility 1322:1329 motility 1322:1329 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 8 46 gly glycosylation 887:899 arg2 sites 901:905 particular glycosylation sites 876:905 particular glycosylation sites 876:905 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 0 47 gly glycosylation 14:26 arg1 flagellin 68:76 the Aeromonas caviae flagellin 47:76 the Aeromonas caviae flagellin 47:76 Heterogeneous glycosylation and methylation of the Aeromonas caviae flagellin. 36031959 10 48 theme flagellin 1349:1357 arg1 flagellin 1349:1357 flagellin 1349:1357 flagellin 1349:1357 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 48 theme flagellin 1349:1357 arg1 amount 1339:1344 the amount 1335:1344 the amount of flagellin present in the cells 1335:1378 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 48 theme flagellin 1349:1357 arg1 reduction 1309:1317 a reduction 1307:1317 a reduction in motility 1307:1329 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 0 49 theme caviae 61:66 arg1 flagellin 68:76 the Aeromonas caviae flagellin 47:76 the Aeromonas caviae flagellin 47:76 Heterogeneous glycosylation and methylation of the Aeromonas caviae flagellin. 36031959 10 50 from cells 1374:1378 arg1 present 1359:1365 present 1359:1365 present 1359:1365 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 7 51 gly glycosylated 833:844 arg1 sites 806:810 no serine or threonine sites 783:810 no serine or threonine sites that were constantly glycosylated 783:844 Using mass spectrometry it was revealed that pseudaminic acid O-glycosylation was heterogeneous with no serine or threonine sites that were constantly glycosylated. 36031959 0 52 theme Aeromonas 51:59 arg1 flagellin 68:76 the Aeromonas caviae flagellin 47:76 the Aeromonas caviae flagellin 47:76 Heterogeneous glycosylation and methylation of the Aeromonas caviae flagellin. 36031959 7 53 theme acid 739:742 arg1 O-glycosylation 744:758 pseudaminic acid O-glycosylation 727:758 pseudaminic acid O-glycosylation 727:758 Using mass spectrometry it was revealed that pseudaminic acid O-glycosylation was heterogeneous with no serine or threonine sites that were constantly glycosylated. 36031959 9 54 link O-linked 1038:1045 arg1 glycosylation 1047:1059 flagellin O-linked glycosylation 1028:1059 flagellin O-linked glycosylation 1028:1059 For flagellin O-linked glycosylation, there is no known consensus sequence, although hydrophobic amino acids have been suggested to play a role. 36031959 8 55 from mutagenesis 861:871 arg1 cases 915:919 most cases 910:919 most cases 910:919 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 10 56 theme residues 1245:1252 arg1 mutagenesis 1208:1218 site-directed mutagenesis 1194:1218 site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation 1194:1288 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 57 gly glycosylation 1276:1288 arg2 glycosylation 1276:1288 glycosylation 1276:1288 glycosylation 1276:1288 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 57 gly glycosylation 1276:1288 arg2 sites 1267:1271 the sites 1263:1271 the sites of glycosylation 1263:1288 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 58 theme amino 1421:1425 arg1 acids 1427:1431 these hydrophobic amino acids 1403:1431 these hydrophobic amino acids 1403:1431 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 59 theme leucine 1237:1243 arg1 residues 1245:1252 isoleucine or leucine residues 1223:1252 isoleucine or leucine residues flanking the sites of glycosylation 1223:1288 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 60 from role 1394:1397 arg1 process 1464:1470 the flagellin glycosylation process 1436:1470 the flagellin glycosylation process 1436:1470 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 2 61 gly O-glycosylate 193:205 arg1 flagellins 213:222 their flagellins 207:222 their flagellins 207:222 Many bacteria are now known to be able to O-glycosylate their flagellins, the proteins that make up the flagellar filament. 36031959 2 61 gly O-glycosylate 193:205 arg1 proteins 229:236 the proteins 225:236 the proteins that make up the flagellar filament 225:272 Many bacteria are now known to be able to O-glycosylate their flagellins, the proteins that make up the flagellar filament. 36031959 10 62 theme glycosylation 1276:1288 arg1 glycosylation 1276:1288 glycosylation 1276:1288 glycosylation 1276:1288 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 62 theme glycosylation 1276:1288 arg1 sites 1267:1271 the sites 1263:1271 the sites of glycosylation 1263:1288 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 8 63 theme reduced 950:956 arg1 motility 958:965 reduced motility 950:965 reduced motility 950:965 Site-directed mutagenesis of particular glycosylation sites in most cases resulted in strains that had reduced motility and produced less detectable flagellin on Western blots. 36031959 1 64 theme flagellar 131:139 arg1 filament 141:148 a flagellar filament 129:148 a flagellar filament 129:148 Bacterial swimming is mediated by the rotation of a flagellar filament. 36031959 9 65 theme O-linked 1038:1045 arg1 glycosylation 1047:1059 flagellin O-linked glycosylation 1028:1059 flagellin O-linked glycosylation 1028:1059 For flagellin O-linked glycosylation, there is no known consensus sequence, although hydrophobic amino acids have been suggested to play a role. 36031959 7 66 theme pseudaminic 727:737 arg1 O-glycosylation 744:758 pseudaminic acid O-glycosylation 727:758 pseudaminic acid O-glycosylation 727:758 Using mass spectrometry it was revealed that pseudaminic acid O-glycosylation was heterogeneous with no serine or threonine sites that were constantly glycosylated. 36031959 1 67 theme filament 141:148 arg1 rotation 117:124 the rotation 113:124 the rotation of a flagellar filament 113:148 Bacterial swimming is mediated by the rotation of a flagellar filament. 36031959 9 68 theme flagellin 1028:1036 arg1 glycosylation 1047:1059 flagellin O-linked glycosylation 1028:1059 flagellin O-linked glycosylation 1028:1059 For flagellin O-linked glycosylation, there is no known consensus sequence, although hydrophobic amino acids have been suggested to play a role. 36031959 10 69 attach present 1359:1365 arg2 flagellin 1349:1357 flagellin 1349:1357 flagellin 1349:1357 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 69 attach present 1359:1365 arg2 amount 1339:1344 the amount 1335:1344 the amount of flagellin present in the cells 1335:1378 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 10 69 attach present 1359:1365 arg1 cells 1374:1378 the cells 1370:1378 the cells 1370:1378 We, therefore, performed site-directed mutagenesis of isoleucine or leucine residues flanking the sites of glycosylation and demonstrated a reduction in motility and the amount of flagellin present in the cells, indicating a role for these hydrophobic amino acids in the flagellin glycosylation process. 36031959 0 70 theme flagellin 68:76 arg1 methylation 32:42 methylation 32:42 methylation 32:42 Heterogeneous glycosylation and methylation of the Aeromonas caviae flagellin. 36031959 0 70 theme flagellin 68:76 arg1 glycosylation 14:26 Heterogeneous glycosylation 0:26 Heterogeneous glycosylation 0:26 Heterogeneous glycosylation and methylation of the Aeromonas caviae flagellin. 35289036 3 0 gly glycopeptides 566:578 arg2 glycopeptides 566:578 the enriched glycopeptides 553:578 the enriched glycopeptides 553:578 The attached glycans on the enriched glycopeptides are removed by wild-type Endo-M/S to restore the O-GlcNAc moiety. 35289036 1 1 theme original 193:200 arg1 form 202:205 their original form 187:205 their original form from complex samples 187:226 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 3 2 from glycans 542:548 arg1 glycopeptides 566:578 the enriched glycopeptides 553:578 the enriched glycopeptides 553:578 The attached glycans on the enriched glycopeptides are removed by wild-type Endo-M/S to restore the O-GlcNAc moiety. 35289036 3 3 theme wild-type 595:603 arg1 Endo-M/S 605:612 wild-type Endo-M/S 595:612 wild-type Endo-M/S 595:612 The attached glycans on the enriched glycopeptides are removed by wild-type Endo-M/S to restore the O-GlcNAc moiety. 35289036 1 4 theme proteomic 297:305 arg1 analysis 307:314 proteomic analysis 297:314 proteomic analysis 297:314 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 1 5 from peptides 175:182 arg1 form 202:205 their original form 187:205 their original form from complex samples 187:226 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 1 5 from peptides 175:182 arg1 samples 220:226 complex samples 212:226 complex samples 212:226 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 3 6 theme attached 533:540 arg1 glycans 542:548 The attached glycans 529:548 The attached glycans on the enriched glycopeptides 529:578 The attached glycans on the enriched glycopeptides are removed by wild-type Endo-M/S to restore the O-GlcNAc moiety. 35289036 4 7 gly glycopeptide 793:804 arg2 glycopeptide 793:804 glycopeptide detection 793:814 glycopeptide detection 793:814 Compared with classic chemoenzymatic labeling, this approach enables the tag-free identification, and eliminates the interference of bulky tags in glycopeptide detection. 35289036 2 8 theme long 374:377 arg1 N-glycans 379:387 long N-glycans 374:387 long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC) 374:526 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 5 9 theme O-GlcNAcylation 898:912 arg1 analysis 878:885 the proteome-wide analysis 860:885 the proteome-wide analysis of protein O-GlcNAcylation to promote its mechanism research 860:946 This approach presents a unique avenue for the proteome-wide analysis of protein O-GlcNAcylation to promote its mechanism research. 35289036 3 10 theme enriched 557:564 arg1 glycopeptides 566:578 the enriched glycopeptides 553:578 the enriched glycopeptides 553:578 The attached glycans on the enriched glycopeptides are removed by wild-type Endo-M/S to restore the O-GlcNAc moiety. 35289036 4 11 theme tag-free 719:726 arg1 identification 728:741 the tag-free identification 715:741 the tag-free identification 715:741 Compared with classic chemoenzymatic labeling, this approach enables the tag-free identification, and eliminates the interference of bulky tags in glycopeptide detection. 35289036 2 12 theme interaction 486:496 arg1 HILIC 521:525 HILIC 521:525 HILIC 521:525 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 2 12 theme interaction 486:496 arg1 chromatography 505:518 hydrophilic interaction liquid chromatography 474:518 hydrophilic interaction liquid chromatography (HILIC) 474:526 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 5 13 theme proteome-wide 864:876 arg1 analysis 878:885 the proteome-wide analysis 860:885 the proteome-wide analysis of protein O-GlcNAcylation to promote its mechanism research 860:946 This approach presents a unique avenue for the proteome-wide analysis of protein O-GlcNAcylation to promote its mechanism research. 35289036 5 14 theme mechanism 929:937 arg1 research 939:946 its mechanism research 925:946 its mechanism research 925:946 This approach presents a unique avenue for the proteome-wide analysis of protein O-GlcNAcylation to promote its mechanism research. 35289036 0 15 theme Mediated 7:14 arg1 Approach 31:38 Endo-M Mediated Chemoenzymatic Approach 0:38 Endo-M Mediated Chemoenzymatic Approach 0:38 Endo-M Mediated Chemoenzymatic Approach Enables Reversible Glycopeptide Labeling for O-GlcNAcylation Analysis. 35289036 1 16 theme complex 212:218 arg1 samples 220:226 complex samples 212:226 complex samples 212:226 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 0 17 theme Endo-M 0:5 arg1 Approach 31:38 Endo-M Mediated Chemoenzymatic Approach 0:38 Endo-M Mediated Chemoenzymatic Approach 0:38 Endo-M Mediated Chemoenzymatic Approach Enables Reversible Glycopeptide Labeling for O-GlcNAcylation Analysis. 35289036 2 18 theme O-GlcNAc 339:346 arg1 moieties 348:355 the O-GlcNAc moieties 335:355 the O-GlcNAc moieties 335:355 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 2 19 theme glycopeptides 457:469 arg1 enrichment 431:440 the enrichment 427:440 the enrichment of the labeled glycopeptides 427:469 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 4 20 theme tags 785:788 arg1 interference 763:774 the interference 759:774 the interference of bulky tags in glycopeptide detection 759:814 Compared with classic chemoenzymatic labeling, this approach enables the tag-free identification, and eliminates the interference of bulky tags in glycopeptide detection. 35289036 5 21 theme protein 890:896 arg1 O-GlcNAcylation 898:912 protein O-GlcNAcylation 890:912 protein O-GlcNAcylation 890:912 This approach presents a unique avenue for the proteome-wide analysis of protein O-GlcNAcylation to promote its mechanism research. 35289036 0 22 theme Chemoenzymatic 16:29 arg1 Approach 31:38 Endo-M Mediated Chemoenzymatic Approach 0:38 Endo-M Mediated Chemoenzymatic Approach 0:38 Endo-M Mediated Chemoenzymatic Approach Enables Reversible Glycopeptide Labeling for O-GlcNAcylation Analysis. 35289036 1 23 theme O-linked 133:140 arg1 O-GlcNAc 165:172 O-GlcNAc 165:172 O-GlcNAc 165:172 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 1 23 theme O-linked 133:140 arg1 β-N-acetylglucosamine 142:162 O-linked β-N-acetylglucosamine 133:162 O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples 133:226 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 4 24 theme chemoenzymatic 668:681 arg1 labeling 683:690 classic chemoenzymatic labeling 660:690 classic chemoenzymatic labeling 660:690 Compared with classic chemoenzymatic labeling, this approach enables the tag-free identification, and eliminates the interference of bulky tags in glycopeptide detection. 35289036 0 25 theme Reversible 48:57 arg1 Labeling 72:79 Reversible Glycopeptide Labeling 48:79 Reversible Glycopeptide Labeling for O-GlcNAcylation Analysis 48:108 Endo-M Mediated Chemoenzymatic Approach Enables Reversible Glycopeptide Labeling for O-GlcNAcylation Analysis. 35289036 3 26 theme O-GlcNAc 629:636 arg1 moiety 638:643 the O-GlcNAc moiety 625:643 the O-GlcNAc moiety 625:643 The attached glycans on the enriched glycopeptides are removed by wild-type Endo-M/S to restore the O-GlcNAc moiety. 35289036 5 27 theme unique 842:847 arg1 avenue 849:854 a unique avenue 840:854 a unique avenue for the proteome-wide analysis of protein O-GlcNAcylation to promote its mechanism research 840:946 This approach presents a unique avenue for the proteome-wide analysis of protein O-GlcNAcylation to promote its mechanism research. 35289036 4 28 theme classic 660:666 arg1 labeling 683:690 classic chemoenzymatic labeling 660:690 classic chemoenzymatic labeling 660:690 Compared with classic chemoenzymatic labeling, this approach enables the tag-free identification, and eliminates the interference of bulky tags in glycopeptide detection. 35289036 2 29 theme labeled 449:455 arg1 glycopeptides 457:469 the labeled glycopeptides 445:469 the labeled glycopeptides 445:469 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 2 30 theme liquid 498:503 arg1 HILIC 521:525 HILIC 521:525 HILIC 521:525 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 2 30 theme liquid 498:503 arg1 chromatography 505:518 hydrophilic interaction liquid chromatography 474:518 hydrophilic interaction liquid chromatography (HILIC) 474:526 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 1 31 theme β-N-acetylglucosamine 142:162 arg1 peptides 175:182 O-linked β-N-acetylglucosamine (O-GlcNAc) peptides 133:182 O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples 133:226 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 0 32 theme Glycopeptide 59:70 arg1 Labeling 72:79 Reversible Glycopeptide Labeling 48:79 Reversible Glycopeptide Labeling for O-GlcNAcylation Analysis 48:108 Endo-M Mediated Chemoenzymatic Approach Enables Reversible Glycopeptide Labeling for O-GlcNAcylation Analysis. 35289036 4 33 theme bulky 779:783 arg1 tags 785:788 bulky tags 779:788 bulky tags 779:788 Compared with classic chemoenzymatic labeling, this approach enables the tag-free identification, and eliminates the interference of bulky tags in glycopeptide detection. 35289036 1 34 theme first 243:247 arg1 approach 284:291 the first reversible chemoenzymatic labeling approach 239:291 the first reversible chemoenzymatic labeling approach for proteomic analysis 239:314 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 4 35 theme glycopeptide 793:804 arg1 detection 806:814 glycopeptide detection 793:814 glycopeptide detection 793:814 Compared with classic chemoenzymatic labeling, this approach enables the tag-free identification, and eliminates the interference of bulky tags in glycopeptide detection. 35289036 4 36 from interference 763:774 arg1 detection 806:814 glycopeptide detection 793:814 glycopeptide detection 793:814 Compared with classic chemoenzymatic labeling, this approach enables the tag-free identification, and eliminates the interference of bulky tags in glycopeptide detection. 35289036 1 37 theme reversible 249:258 arg1 approach 284:291 the first reversible chemoenzymatic labeling approach 239:291 the first reversible chemoenzymatic labeling approach for proteomic analysis 239:314 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 0 38 theme O-GlcNAcylation 85:99 arg1 Analysis 101:108 O-GlcNAcylation Analysis 85:108 O-GlcNAcylation Analysis 85:108 Endo-M Mediated Chemoenzymatic Approach Enables Reversible Glycopeptide Labeling for O-GlcNAcylation Analysis. 35289036 1 39 from samples 220:226 arg1 form 202:205 their original form 187:205 their original form from complex samples 187:226 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 1 39 from samples 220:226 arg1 peptides 175:182 O-linked β-N-acetylglucosamine (O-GlcNAc) peptides 133:182 O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples 133:226 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 2 40 theme Endo-M 398:403 arg1 mutant 405:410 an Endo-M mutant 395:410 an Endo-M mutant 395:410 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 1 41 theme chemoenzymatic 260:273 arg1 approach 284:291 the first reversible chemoenzymatic labeling approach 239:291 the first reversible chemoenzymatic labeling approach for proteomic analysis 239:314 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 1 42 link O-linked 133:140 arg1 O-GlcNAc 165:172 O-GlcNAc 165:172 O-GlcNAc 165:172 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 1 42 link O-linked 133:140 arg1 β-N-acetylglucosamine 142:162 O-linked β-N-acetylglucosamine 133:162 O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples 133:226 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 35289036 2 43 gly glycopeptides 457:469 arg2 glycopeptides 457:469 the labeled glycopeptides 445:469 the labeled glycopeptides 445:469 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 2 44 theme hydrophilic 474:484 arg1 HILIC 521:525 HILIC 521:525 HILIC 521:525 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 2 44 theme hydrophilic 474:484 arg1 chromatography 505:518 hydrophilic interaction liquid chromatography 474:518 hydrophilic interaction liquid chromatography (HILIC) 474:526 In this strategy, the O-GlcNAc moieties are ligated with long N-glycans using an Endo-M mutant, which enables the enrichment of the labeled glycopeptides by hydrophilic interaction liquid chromatography (HILIC). 35289036 1 45 theme labeling 275:282 arg1 approach 284:291 the first reversible chemoenzymatic labeling approach 239:291 the first reversible chemoenzymatic labeling approach for proteomic analysis 239:314 To selectively enrich O-linked β-N-acetylglucosamine (O-GlcNAc) peptides in their original form from complex samples, we report the first reversible chemoenzymatic labeling approach for proteomic analysis. 36904450 10 0 theme glycerol 1670:1677 arg1 g/L 1648:1650 20 g/L 1645:1650 20 g/L of SLN 1645:1657 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 10 0 theme glycerol 1670:1677 arg1 g/L 1686:1688 3 g/L 1684:1688 3 g/L of XG 1684:1694 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 10 0 theme glycerol 1670:1677 arg1 g/L 1663:1665 30 g/L 1660:1665 30 g/L of glycerol 1660:1677 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 10 1 theme appropriate 1502:1512 arg1 properties 1523:1532 the most appropriate physical properties 1493:1532 the most appropriate physical properties 1493:1532 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 9 2 theme plasticizer 1443:1453 arg1 content 1455:1461 a higher plasticizer content 1434:1461 a higher plasticizer content 1434:1461 Thermal analysis showed an increase in the melting temperature when a higher SLN content was used, whereas a higher plasticizer content reduced it. 36904450 10 3 theme XG 1693:1694 arg1 g/L 1648:1650 20 g/L 1645:1650 20 g/L of SLN 1645:1657 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 10 3 theme XG 1693:1694 arg1 g/L 1686:1688 3 g/L 1684:1688 3 g/L of XG 1684:1694 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 10 3 theme XG 1693:1694 arg1 g/L 1663:1665 30 g/L 1660:1665 30 g/L of glycerol 1660:1677 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 3 4 theme plasticizer 488:498 arg1 concentration 500:512 a plasticizer concentration 486:512 a plasticizer concentration of 10 and 30 g/L 486:529 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 4 5 theme mechanical 741:750 arg1 properties 765:774 the microstructural, thermal, mechanical, and optical properties 711:774 the microstructural, thermal, mechanical, and optical properties 711:774 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 9 6 theme higher 1436:1441 arg1 content 1455:1461 a higher plasticizer content 1434:1461 a higher plasticizer content 1434:1461 Thermal analysis showed an increase in the melting temperature when a higher SLN content was used, whereas a higher plasticizer content reduced it. 36904450 3 7 theme g/L 527:529 arg1 concentration 500:512 a plasticizer concentration 486:512 a plasticizer concentration of 10 and 30 g/L 486:529 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 5 8 dep films 876:880 arg1 films 876:880 the films greater strength and flexibility 872:913 the films greater strength and flexibility 872:913 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 5 8 dep films 876:880 arg1 flexibility 903:913 flexibility 903:913 flexibility 903:913 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 5 8 dep films 876:880 arg1 strength 890:897 greater strength 882:897 greater strength 882:897 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 0 9 theme Support 106:112 arg1 Polysaccharides 114:128 Support Polysaccharides 106:128 Support Polysaccharides 106:128 Study of Candelilla Wax Concentrations on the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides. 36904450 5 10 theme temperature 939:949 arg1 influence 926:934 the influence 922:934 the influence of temperature and relative humidity 922:971 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 10 11 theme extension 1564:1572 arg1 conservation 1596:1607 the packaging, shelf-life extension, and improved quality conservation 1538:1607 the packaging, shelf-life extension, and improved quality conservation of fresh foods 1538:1622 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 5 12 theme relative 955:962 arg1 humidity 964:971 relative humidity 955:971 relative humidity 955:971 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 10 13 theme quality 1588:1594 arg1 conservation 1596:1607 the packaging, shelf-life extension, and improved quality conservation 1538:1607 the packaging, shelf-life extension, and improved quality conservation of fresh foods 1538:1622 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 4 14 theme water 792:796 arg1 barrier 804:810 the water vapor barrier 788:810 the water vapor barrier 788:810 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 9 15 dep showed 1344:1349 arg1 whereas 1426:1432 whereas 1426:1432 whereas 1426:1432 Thermal analysis showed an increase in the melting temperature when a higher SLN content was used, whereas a higher plasticizer content reduced it. 36904450 2 16 dep polydispersity 325:338 arg1 index 340:344 index < 0.31 340:351 polydispersity index < 0.31 325:351 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 2 17 theme resulting 245:253 arg1 suspension 255:264 The resulting suspension 241:264 The resulting suspension 241:264 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 1 18 theme Solid 131:135 arg1 nanoparticles 143:155 Solid lipid nanoparticles 131:155 Solid lipid nanoparticles (SLN) based on candelilla wax 131:185 Solid lipid nanoparticles (SLN) based on candelilla wax were prepared using the hot homogenization technique. 36904450 1 18 theme Solid 131:135 arg1 SLN 158:160 SLN 158:160 SLN 158:160 Solid lipid nanoparticles (SLN) based on candelilla wax were prepared using the hot homogenization technique. 36904450 7 19 theme concentrations 1171:1184 arg1 function 1155:1162 a function 1153:1162 a function of the concentrations of the SLN and plasticizer 1153:1211 The arrangement of the SLN in the polymeric networks showed changes in the distribution as a function of the concentrations of the SLN and plasticizer. 36904450 7 19 theme concentrations 1171:1184 arg1 changes 1122:1128 changes 1122:1128 changes in the distribution 1122:1148 The arrangement of the SLN in the polymeric networks showed changes in the distribution as a function of the concentrations of the SLN and plasticizer. 36904450 10 20 theme foods 1618:1622 arg1 conservation 1596:1607 the packaging, shelf-life extension, and improved quality conservation 1538:1607 the packaging, shelf-life extension, and improved quality conservation of fresh foods 1538:1622 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 9 21 from increase 1354:1361 arg1 temperature 1378:1388 the melting temperature 1366:1388 the melting temperature 1366:1388 Thermal analysis showed an increase in the melting temperature when a higher SLN content was used, whereas a higher plasticizer content reduced it. 36904450 0 22 theme Edible 69:74 arg1 Nanocoatings 76:87 Edible Nanocoatings 69:87 Edible Nanocoatings as a Function of Support Polysaccharides 69:128 Study of Candelilla Wax Concentrations on the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides. 36904450 0 23 from Study 0:4 arg1 Properties 55:64 the Physical Properties 42:64 the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides 42:128 Study of Candelilla Wax Concentrations on the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides. 36904450 4 24 theme film 668:671 arg1 composition 673:683 film composition 668:683 film composition 668:683 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 5 25 theme SLN 847:849 arg1 SLN 847:849 SLN 847:849 SLN 847:849 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 5 25 theme SLN 847:849 arg1 amounts 836:842 Higher amounts 829:842 Higher amounts of SLN and plasticizer 829:865 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 5 25 theme SLN 847:849 arg1 plasticizer 855:865 plasticizer 855:865 plasticizer 855:865 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 8 26 theme 3.34-7.93 1316:1324 arg1 values 1306:1311 values 1306:1311 values of 3.34-7.93 1306:1324 The total color difference (ΔE) was greater when the content of the SLN was increased, with values of 3.34-7.93. 36904450 5 27 theme plasticizer 855:865 arg1 SLN 847:849 SLN 847:849 SLN 847:849 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 5 27 theme plasticizer 855:865 arg1 amounts 836:842 Higher amounts 829:842 Higher amounts of SLN and plasticizer 829:865 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 5 27 theme plasticizer 855:865 arg1 plasticizer 855:865 plasticizer 855:865 plasticizer 855:865 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 2 28 theme zeta 358:361 arg1 potential 363:371 zeta potential 358:371 zeta potential of -3.5 mV 358:382 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 2 29 contain had 266:268 arg2 behavior 280:287 monomodal behavior 270:287 monomodal behavior 270:287 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 2 29 contain had 266:268 arg1 suspension 255:264 The resulting suspension 241:264 The resulting suspension 241:264 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 4 30 from effects 644:650 arg1 properties 765:774 the microstructural, thermal, mechanical, and optical properties 711:774 the microstructural, thermal, mechanical, and optical properties 711:774 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 4 30 from effects 644:650 arg1 barrier 804:810 the water vapor barrier 788:810 the water vapor barrier 788:810 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 9 31 theme melting 1370:1376 arg1 temperature 1378:1388 the melting temperature 1366:1388 the melting temperature 1366:1388 Thermal analysis showed an increase in the melting temperature when a higher SLN content was used, whereas a higher plasticizer content reduced it. 36904450 4 32 theme temperature 655:665 arg1 effects 644:650 The effects 640:650 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, 640:811 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 4 33 theme microstructural 715:729 arg1 properties 765:774 the microstructural, thermal, mechanical, and optical properties 711:774 the microstructural, thermal, mechanical, and optical properties 711:774 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 10 34 theme Edible 1475:1480 arg1 films 1482:1486 Edible films 1475:1486 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods 1475:1622 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 0 35 theme Candelilla 9:18 arg1 Concentrations 24:37 Candelilla Wax Concentrations 9:37 Candelilla Wax Concentrations 9:37 Study of Candelilla Wax Concentrations on the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides. 36904450 10 36 theme packaging 1542:1550 arg1 conservation 1596:1607 the packaging, shelf-life extension, and improved quality conservation 1538:1607 the packaging, shelf-life extension, and improved quality conservation of fresh foods 1538:1622 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 8 37 theme color 1224:1228 arg1 difference 1230:1239 The total color difference 1214:1239 The total color difference (ΔE) 1214:1244 The total color difference (ΔE) was greater when the content of the SLN was increased, with values of 3.34-7.93. 36904450 8 37 theme color 1224:1228 arg1 ΔE 1242:1243 ΔE 1242:1243 ΔE 1242:1243 The total color difference (ΔE) was greater when the content of the SLN was increased, with values of 3.34-7.93. 36904450 8 37 theme color 1224:1228 arg1 greater 1250:1256 greater 1250:1256 greater 1250:1256 The total color difference (ΔE) was greater when the content of the SLN was increased, with values of 3.34-7.93. 36904450 2 38 theme mV 381:382 arg1 potential 363:371 zeta potential 358:371 zeta potential of -3.5 mV 358:382 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 2 38 theme mV 381:382 arg1 polydispersity 325:338 polydispersity 325:338 polydispersity index < 0.31 325:351 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 2 38 theme mV 381:382 arg1 size 305:308 a particle size 294:308 a particle size of 809-885 nm 294:322 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 0 39 theme Concentrations 24:37 arg1 Study 0:4 Study 0:4 Study of Candelilla Wax Concentrations on the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides. 0:129 Study of Candelilla Wax Concentrations on the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides. 36904450 9 40 theme higher 1397:1402 arg1 content 1408:1414 a higher SLN content 1395:1414 a higher SLN content 1395:1414 Thermal analysis showed an increase in the melting temperature when a higher SLN content was used, whereas a higher plasticizer content reduced it. 36904450 3 41 theme xanthan 580:586 arg1 gum 588:590 xanthan gum 580:590 xanthan gum (XG) 580:595 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 3 41 theme xanthan 580:586 arg1 stabilizers 551:561 the polysaccharide stabilizers 532:561 the polysaccharide stabilizers used 532:566 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 3 41 theme xanthan 580:586 arg1 XG 593:594 XG 593:594 XG 593:594 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 4 42 theme thermal 732:738 arg1 properties 765:774 the microstructural, thermal, mechanical, and optical properties 711:774 the microstructural, thermal, mechanical, and optical properties 711:774 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 10 43 theme most 1497:1500 arg1 properties 1523:1532 the most appropriate physical properties 1493:1532 the most appropriate physical properties 1493:1532 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 9 44 used used 1420:1423 arg2 content 1408:1414 a higher SLN content 1395:1414 a higher SLN content 1395:1414 Thermal analysis showed an increase in the melting temperature when a higher SLN content was used, whereas a higher plasticizer content reduced it. 36904450 3 45 theme carboxymethyl 600:612 arg1 CMC 625:627 CMC 625:627 CMC 625:627 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 3 45 theme carboxymethyl 600:612 arg1 cellulose 614:622 carboxymethyl cellulose 600:622 carboxymethyl cellulose (CMC) 600:628 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 4 46 theme relative 690:697 arg1 humidity 699:706 relative humidity 690:706 relative humidity 690:706 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 3 47 theme SLN 439:441 arg1 each 476:479 each 476:479 each 476:479 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 3 47 theme SLN 439:441 arg1 concentrations 443:456 SLN concentrations 439:456 SLN concentrations of 20 and 60 g/L 439:473 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 10 48 theme SLN 1655:1657 arg1 g/L 1648:1650 20 g/L 1645:1650 20 g/L of SLN 1645:1657 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 10 48 theme SLN 1655:1657 arg1 g/L 1686:1688 3 g/L 1684:1688 3 g/L of XG 1684:1694 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 10 48 theme SLN 1655:1657 arg1 g/L 1663:1665 30 g/L 1660:1665 30 g/L of glycerol 1660:1677 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 3 49 theme g/L 471:473 arg1 each 476:479 each 476:479 each 476:479 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 3 49 theme g/L 471:473 arg1 concentrations 443:456 SLN concentrations 439:456 SLN concentrations of 20 and 60 g/L 439:473 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 1 50 theme homogenization 215:228 arg1 technique 230:238 the hot homogenization technique 207:238 the hot homogenization technique 207:238 Solid lipid nanoparticles (SLN) based on candelilla wax were prepared using the hot homogenization technique. 36904450 5 51 theme greater 882:888 arg1 films 876:880 the films greater strength and flexibility 872:913 the films greater strength and flexibility 872:913 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 5 51 theme greater 882:888 arg1 strength 890:897 greater strength 882:897 greater strength 882:897 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 6 52 theme water 978:982 arg1 WVP 1004:1006 WVP 1004:1006 WVP 1004:1006 The water vapor permeability (WVP) was lower when 60 g/L of SLN was added to the films. 36904450 6 52 theme water 978:982 arg1 lower 1013:1017 lower 1013:1017 lower 1013:1017 The water vapor permeability (WVP) was lower when 60 g/L of SLN was added to the films. 36904450 6 52 theme water 978:982 arg1 permeability 990:1001 The water vapor permeability 974:1001 The water vapor permeability (WVP) 974:1007 The water vapor permeability (WVP) was lower when 60 g/L of SLN was added to the films. 36904450 10 53 theme physical 1514:1521 arg1 properties 1523:1532 the most appropriate physical properties 1493:1532 the most appropriate physical properties 1493:1532 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 4 54 theme optical 757:763 arg1 properties 765:774 the microstructural, thermal, mechanical, and optical properties 711:774 the microstructural, thermal, mechanical, and optical properties 711:774 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 7 55 theme SLN 1085:1087 arg1 arrangement 1066:1076 The arrangement 1062:1076 The arrangement of the SLN in the polymeric networks 1062:1113 The arrangement of the SLN in the polymeric networks showed changes in the distribution as a function of the concentrations of the SLN and plasticizer. 36904450 10 56 theme shelf-life 1553:1562 arg1 extension 1564:1572 shelf-life extension 1553:1572 shelf-life extension 1553:1572 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 6 57 theme SLN 1034:1036 arg1 g/L 1027:1029 60 g/L 1024:1029 60 g/L of SLN 1024:1036 The water vapor permeability (WVP) was lower when 60 g/L of SLN was added to the films. 36904450 2 58 theme monomodal 270:278 arg1 behavior 280:287 monomodal behavior 270:287 monomodal behavior 270:287 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 10 59 theme improved 1579:1586 arg1 quality 1588:1594 improved quality 1579:1594 improved quality 1579:1594 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 3 60 from g/L 635:637 arg1 gum 588:590 xanthan gum 580:590 xanthan gum (XG) 580:595 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 3 60 from g/L 635:637 arg1 stabilizers 551:561 the polysaccharide stabilizers 532:561 the polysaccharide stabilizers used 532:566 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 3 60 from g/L 635:637 arg1 cellulose 614:622 carboxymethyl cellulose 600:622 carboxymethyl cellulose (CMC) 600:628 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 3 60 from g/L 635:637 arg1 XG 593:594 XG 593:594 XG 593:594 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 3 60 from g/L 635:637 arg1 CMC 625:627 CMC 625:627 CMC 625:627 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 0 61 theme Polysaccharides 114:128 arg1 Function 94:101 a Function 92:101 a Function of Support Polysaccharides 92:128 Study of Candelilla Wax Concentrations on the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides. 36904450 2 62 theme particle 296:303 arg1 size 305:308 a particle size 294:308 a particle size of 809-885 nm 294:322 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 4 63 theme vapor 798:802 arg1 barrier 804:810 the water vapor barrier 788:810 the water vapor barrier 788:810 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 10 64 theme fresh 1612:1616 arg1 foods 1618:1622 fresh foods 1612:1622 fresh foods 1612:1622 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 1 65 theme candelilla 172:181 arg1 wax 183:185 candelilla wax 172:185 candelilla wax 172:185 Solid lipid nanoparticles (SLN) based on candelilla wax were prepared using the hot homogenization technique. 36904450 5 66 theme humidity 964:971 arg1 influence 926:934 the influence 922:934 the influence of temperature and relative humidity 922:971 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 8 67 theme SLN 1282:1284 arg1 content 1267:1273 the content 1263:1273 the content of the SLN 1263:1284 The total color difference (ΔE) was greater when the content of the SLN was increased, with values of 3.34-7.93. 36904450 7 68 theme plasticizer 1201:1211 arg1 concentrations 1171:1184 the concentrations 1167:1184 the concentrations of the SLN and plasticizer 1167:1211 The arrangement of the SLN in the polymeric networks showed changes in the distribution as a function of the concentrations of the SLN and plasticizer. 36904450 7 69 from changes 1122:1128 arg1 distribution 1137:1148 the distribution 1133:1148 the distribution 1133:1148 The arrangement of the SLN in the polymeric networks showed changes in the distribution as a function of the concentrations of the SLN and plasticizer. 36904450 7 70 from arrangement 1066:1076 arg1 networks 1106:1113 the polymeric networks 1092:1113 the polymeric networks 1092:1113 The arrangement of the SLN in the polymeric networks showed changes in the distribution as a function of the concentrations of the SLN and plasticizer. 36904450 7 71 theme SLN 1193:1195 arg1 concentrations 1171:1184 the concentrations 1167:1184 the concentrations of the SLN and plasticizer 1167:1211 The arrangement of the SLN in the polymeric networks showed changes in the distribution as a function of the concentrations of the SLN and plasticizer. 36904450 2 72 dep size 305:308 arg1 weeks 386:390 5 weeks 384:390 5 weeks after monitoring 384:407 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 2 73 theme nm 321:322 arg1 potential 363:371 zeta potential 358:371 zeta potential of -3.5 mV 358:382 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 2 73 theme nm 321:322 arg1 polydispersity 325:338 polydispersity 325:338 polydispersity index < 0.31 325:351 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 2 73 theme nm 321:322 arg1 size 305:308 a particle size 294:308 a particle size of 809-885 nm 294:322 The resulting suspension had monomodal behavior with a particle size of 809-885 nm; polydispersity index < 0.31, and zeta potential of -3.5 mV 5 weeks after monitoring. 36904450 3 74 theme polysaccharide 536:549 arg1 gum 588:590 xanthan gum 580:590 xanthan gum (XG) 580:595 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 3 74 theme polysaccharide 536:549 arg1 stabilizers 551:561 the polysaccharide stabilizers 532:561 the polysaccharide stabilizers used 532:566 The films were prepared with SLN concentrations of 20 and 60 g/L, each with a plasticizer concentration of 10 and 30 g/L; the polysaccharide stabilizers used were either xanthan gum (XG) or carboxymethyl cellulose (CMC) at 3 g/L. 36904450 1 75 theme lipid 137:141 arg1 nanoparticles 143:155 Solid lipid nanoparticles 131:155 Solid lipid nanoparticles (SLN) based on candelilla wax 131:185 Solid lipid nanoparticles (SLN) based on candelilla wax were prepared using the hot homogenization technique. 36904450 1 75 theme lipid 137:141 arg1 SLN 158:160 SLN 158:160 SLN 158:160 Solid lipid nanoparticles (SLN) based on candelilla wax were prepared using the hot homogenization technique. 36904450 0 76 theme Nanocoatings 76:87 arg1 Properties 55:64 the Physical Properties 42:64 the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides 42:128 Study of Candelilla Wax Concentrations on the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides. 36904450 9 77 theme Thermal 1327:1333 arg1 analysis 1335:1342 Thermal analysis 1327:1342 Thermal analysis 1327:1342 Thermal analysis showed an increase in the melting temperature when a higher SLN content was used, whereas a higher plasticizer content reduced it. 36904450 4 78 theme composition 673:683 arg1 effects 644:650 The effects 640:650 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, 640:811 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36904450 0 79 theme Wax 20:22 arg1 Concentrations 24:37 Candelilla Wax Concentrations 9:37 Candelilla Wax Concentrations 9:37 Study of Candelilla Wax Concentrations on the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides. 36904450 5 80 theme Higher 829:834 arg1 SLN 847:849 SLN 847:849 SLN 847:849 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 5 80 theme Higher 829:834 arg1 amounts 836:842 Higher amounts 829:842 Higher amounts of SLN and plasticizer 829:865 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 5 80 theme Higher 829:834 arg1 plasticizer 855:865 plasticizer 855:865 plasticizer 855:865 Higher amounts of SLN and plasticizer gave the films greater strength and flexibility due to the influence of temperature and relative humidity. 36904450 10 81 with films 1482:1486 arg1 properties 1523:1532 the most appropriate physical properties 1493:1532 the most appropriate physical properties 1493:1532 Edible films with the most appropriate physical properties for the packaging, shelf-life extension, and improved quality conservation of fresh foods were those made with 20 g/L of SLN, 30 g/L of glycerol, and 3 g/L of XG. 36904450 8 82 theme total 1218:1222 arg1 difference 1230:1239 The total color difference 1214:1239 The total color difference (ΔE) 1214:1244 The total color difference (ΔE) was greater when the content of the SLN was increased, with values of 3.34-7.93. 36904450 8 82 theme total 1218:1222 arg1 ΔE 1242:1243 ΔE 1242:1243 ΔE 1242:1243 The total color difference (ΔE) was greater when the content of the SLN was increased, with values of 3.34-7.93. 36904450 8 82 theme total 1218:1222 arg1 greater 1250:1256 greater 1250:1256 greater 1250:1256 The total color difference (ΔE) was greater when the content of the SLN was increased, with values of 3.34-7.93. 36904450 0 83 theme Physical 46:53 arg1 Properties 55:64 the Physical Properties 42:64 the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides 42:128 Study of Candelilla Wax Concentrations on the Physical Properties of Edible Nanocoatings as a Function of Support Polysaccharides. 36904450 9 84 theme SLN 1404:1406 arg1 content 1408:1414 a higher SLN content 1395:1414 a higher SLN content 1395:1414 Thermal analysis showed an increase in the melting temperature when a higher SLN content was used, whereas a higher plasticizer content reduced it. 36904450 7 85 theme polymeric 1096:1104 arg1 networks 1106:1113 the polymeric networks 1092:1113 the polymeric networks 1092:1113 The arrangement of the SLN in the polymeric networks showed changes in the distribution as a function of the concentrations of the SLN and plasticizer. 36904450 1 86 theme hot 211:213 arg1 technique 230:238 the hot homogenization technique 207:238 the hot homogenization technique 207:238 Solid lipid nanoparticles (SLN) based on candelilla wax were prepared using the hot homogenization technique. 36904450 6 87 theme vapor 984:988 arg1 WVP 1004:1006 WVP 1004:1006 WVP 1004:1006 The water vapor permeability (WVP) was lower when 60 g/L of SLN was added to the films. 36904450 6 87 theme vapor 984:988 arg1 lower 1013:1017 lower 1013:1017 lower 1013:1017 The water vapor permeability (WVP) was lower when 60 g/L of SLN was added to the films. 36904450 6 87 theme vapor 984:988 arg1 permeability 990:1001 The water vapor permeability 974:1001 The water vapor permeability (WVP) 974:1007 The water vapor permeability (WVP) was lower when 60 g/L of SLN was added to the films. 36904450 4 88 theme humidity 699:706 arg1 effects 644:650 The effects 640:650 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, 640:811 The effects of temperature, film composition, and relative humidity on the microstructural, thermal, mechanical, and optical properties, as well as the water vapor barrier, were evaluated. 36807912 5 0 theme negligible 651:660 arg1 effect 662:667 negligible effect 651:667 negligible effect 651:667 The digest enzymes exert negligible effect on the chemical structure of MEP 2. 36807912 6 1 theme larger 800:805 arg1 aggregations 807:818 larger aggregations 800:818 larger aggregations 800:818 Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. 36807912 3 2 theme MEP 513:515 arg1 mice 505:508 diabetic mice 496:508 diabetic mice of MEP 2 496:517 The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2. 36807912 12 3 theme Blood 1490:1494 arg1 level 1504:1508 Blood glucose level 1490:1508 Blood glucose level during the oral glucose tolerance test (OGTT) 1490:1554 Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. 36807912 10 4 theme cell 1374:1377 arg1 infiltration 1379:1390 the inflammatory cell infiltration 1357:1390 the inflammatory cell infiltration 1357:1390 MEP 2 treatment ameliorate the inflammatory cell infiltration and increase the size of pancreas inlets. 36807912 15 5 theme potential 1879:1887 arg1 bioactivities 1902:1914 Its potential antidiabetic bioactivities 1875:1914 Its potential antidiabetic bioactivities 1875:1914 Its potential antidiabetic bioactivities may associate with its α-amylase inhibition and gut microbiome modulation ability. 36807912 9 6 theme α-amylase 1189:1197 arg1 activities 1237:1246 strong α-amylase and moderate α-glucosidase inhibition activities 1182:1246 strong α-amylase and moderate α-glucosidase inhibition activities 1182:1246 Both MEP 2 and its digested components show strong α-amylase and moderate α-glucosidase inhibition activities, leading us to further investigate its ability to modulate the diabetic symptoms. 36807912 13 7 theme gut 1614:1616 arg1 microbiota 1618:1627 gut microbiota 1614:1627 gut microbiota 1614:1627 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 7 8 theme microscope 853:862 arg1 images 870:875 Scanning electron microscope (SEM) images 835:875 Scanning electron microscope (SEM) images 835:875 Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. 36807912 3 9 from composition 481:491 arg1 mice 505:508 diabetic mice 496:508 diabetic mice of MEP 2 496:517 The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2. 36807912 7 10 theme Scanning 835:842 arg1 SEM 865:867 SEM 865:867 SEM 865:867 Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. 36807912 7 10 theme Scanning 835:842 arg1 microscope 853:862 Scanning electron microscope 835:862 Scanning electron microscope (SEM) images 835:875 Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. 36807912 15 11 theme modulation 1979:1988 arg1 ability 1990:1996 gut microbiome modulation ability 1964:1996 gut microbiome modulation ability 1964:1996 Its potential antidiabetic bioactivities may associate with its α-amylase inhibition and gut microbiome modulation ability. 36807912 9 12 theme inhibition 1226:1235 arg1 activities 1237:1246 strong α-amylase and moderate α-glucosidase inhibition activities 1182:1246 strong α-amylase and moderate α-glucosidase inhibition activities 1182:1246 Both MEP 2 and its digested components show strong α-amylase and moderate α-glucosidase inhibition activities, leading us to further investigate its ability to modulate the diabetic symptoms. 36807912 10 13 theme pancreas 1417:1424 arg1 inlets 1426:1431 pancreas inlets 1417:1431 pancreas inlets 1417:1431 MEP 2 treatment ameliorate the inflammatory cell infiltration and increase the size of pancreas inlets. 36807912 15 14 theme gut 1964:1966 arg1 ability 1990:1996 gut microbiome modulation ability 1964:1996 gut microbiome modulation ability 1964:1996 Its potential antidiabetic bioactivities may associate with its α-amylase inhibition and gut microbiome modulation ability. 36807912 0 15 theme microbiota 121:130 arg1 analysis 132:139 microbiota analysis 121:139 microbiota analysis 121:139 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 1 16 theme food 230:233 arg1 applications 235:246 food applications 230:246 food applications 230:246 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 13 17 theme Lachnospiraceae 1779:1793 arg1 species 1795:1801 several Lachnospiraceae species 1771:1801 several Lachnospiraceae species 1771:1801 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 5 18 theme chemical 676:683 arg1 structure 685:693 the chemical structure 672:693 the chemical structure of MEP 2 672:702 The digest enzymes exert negligible effect on the chemical structure of MEP 2. 36807912 1 19 from fungi 191:195 arg1 nutraceuticals 211:224 important nutraceuticals 201:224 important nutraceuticals for food applications 201:246 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 1 19 from fungi 191:195 arg1 polysaccharides 170:184 BACKGROUND Novel functional polysaccharides 142:184 BACKGROUND Novel functional polysaccharides from fungi 142:195 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 0 20 theme Morchella 60:68 arg1 exopolysaccharide 80:96 Morchella esculenta exopolysaccharide 60:96 Morchella esculenta exopolysaccharide 60:96 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 1 21 theme BACKGROUND 142:151 arg1 nutraceuticals 211:224 important nutraceuticals 201:224 important nutraceuticals for food applications 201:246 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 1 21 theme BACKGROUND 142:151 arg1 polysaccharides 170:184 BACKGROUND Novel functional polysaccharides 142:184 BACKGROUND Novel functional polysaccharides from fungi 142:195 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 0 22 theme exopolysaccharide 80:96 arg1 antioxidant 19:29 antioxidant 19:29 antioxidant 19:29 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 0 22 theme exopolysaccharide 80:96 arg1 capacity 48:55 antidiabetic capacity 35:55 antidiabetic capacity 35:55 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 0 22 theme exopolysaccharide 80:96 arg1 profile 10:16 Digestion profile 0:16 Digestion profile 0:16 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 1 23 theme functional 159:168 arg1 nutraceuticals 211:224 important nutraceuticals 201:224 important nutraceuticals for food applications 201:246 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 1 23 theme functional 159:168 arg1 polysaccharides 170:184 BACKGROUND Novel functional polysaccharides 142:184 BACKGROUND Novel functional polysaccharides from fungi 142:195 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 8 24 theme 2,2-Diphenyl-1-picrylhydrazyl 1027:1055 arg1 assay 1131:1135 the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay 1023:1135 the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay 1023:1135 After digestion, the antioxidant ability increases as revealed by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. 36807912 7 25 theme intestinal 935:944 arg1 digestion 946:954 intestinal digestion 935:954 intestinal digestion 935:954 Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. 36807912 11 26 theme HbA1c 1457:1461 arg1 concentration 1440:1452 Serum concentration 1434:1452 Serum concentration of HbA1c 1434:1461 Serum concentration of HbA1c was significantly reduced. 36807912 0 27 theme Digestion 0:8 arg1 profile 10:16 Digestion profile 0:16 Digestion profile 0:16 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 13 28 theme several 1659:1665 arg1 species 1795:1801 several Lachnospiraceae species 1771:1801 several Lachnospiraceae species 1771:1801 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 13 28 theme several 1659:1665 arg1 Alcaligenaceae 1696:1709 Alcaligenaceae 1696:1709 Alcaligenaceae 1696:1709 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 13 28 theme several 1659:1665 arg1 bacteria 1677:1684 several important bacteria 1659:1684 several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species 1659:1801 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 13 28 theme several 1659:1665 arg1 Demequina 1757:1765 Demequina 1757:1765 Demequina 1757:1765 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 13 28 theme several 1659:1665 arg1 Prevotella 1730:1739 Prevotella 1730:1739 Prevotella 1730:1739 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 10 29 theme MEP 1330:1332 arg1 treatment 1336:1344 MEP 2 treatment 1330:1344 MEP 2 treatment 1330:1344 MEP 2 treatment ameliorate the inflammatory cell infiltration and increase the size of pancreas inlets. 36807912 12 30 theme tolerance 1534:1542 arg1 OGTT 1550:1553 OGTT 1550:1553 OGTT 1550:1553 Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. 36807912 12 30 theme tolerance 1534:1542 arg1 test 1544:1547 the oral glucose tolerance test 1517:1547 the oral glucose tolerance test (OGTT) 1517:1554 Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. 36807912 3 31 theme digestion 411:419 arg1 profile 421:427 the digestion profile 407:427 the digestion profile 407:427 The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2. 36807912 4 32 theme in 551:552 arg1 digestion 567:575 in vitro saliva digestion 551:575 in vitro saliva digestion 551:575 RESULTS MEP 2 is stable during in vitro saliva digestion but partially degraded during gastric digestion. 36807912 13 33 theme bacteria 1677:1684 arg1 abundance 1646:1654 the abundance 1642:1654 the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species 1642:1801 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 4 34 theme RESULTS 520:526 arg1 MEP 528:530 RESULTS MEP 2 520:532 RESULTS MEP 2 520:532 RESULTS MEP 2 is stable during in vitro saliva digestion but partially degraded during gastric digestion. 36807912 3 35 theme diabetic 496:503 arg1 mice 505:508 diabetic mice 496:508 diabetic mice of MEP 2 496:517 The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2. 36807912 9 36 theme moderate 1203:1210 arg1 activities 1237:1246 strong α-amylase and moderate α-glucosidase inhibition activities 1182:1246 strong α-amylase and moderate α-glucosidase inhibition activities 1182:1246 Both MEP 2 and its digested components show strong α-amylase and moderate α-glucosidase inhibition activities, leading us to further investigate its ability to modulate the diabetic symptoms. 36807912 6 37 theme microscope 739:748 arg1 images 756:761 Molecular weight and atomic force microscope (AFM) images 705:761 Molecular weight and atomic force microscope (AFM) images 705:761 Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. 36807912 12 38 theme oral 1521:1524 arg1 OGTT 1550:1553 OGTT 1550:1553 OGTT 1550:1553 Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. 36807912 12 38 theme oral 1521:1524 arg1 test 1544:1547 the oral glucose tolerance test 1517:1547 the oral glucose tolerance test (OGTT) 1517:1554 Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. 36807912 10 39 theme inflammatory 1361:1372 arg1 infiltration 1379:1390 the inflammatory cell infiltration 1357:1390 the inflammatory cell infiltration 1357:1390 MEP 2 treatment ameliorate the inflammatory cell infiltration and increase the size of pancreas inlets. 36807912 6 40 theme atomic 726:731 arg1 AFM 751:753 AFM 751:753 AFM 751:753 Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. 36807912 6 40 theme atomic 726:731 arg1 microscope 739:748 atomic force microscope 726:748 atomic force microscope (AFM) 726:754 Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. 36807912 4 41 theme gastric 607:613 arg1 digestion 615:623 gastric digestion 607:623 gastric digestion 607:623 RESULTS MEP 2 is stable during in vitro saliva digestion but partially degraded during gastric digestion. 36807912 15 42 theme antidiabetic 1889:1900 arg1 bioactivities 1902:1914 Its potential antidiabetic bioactivities 1875:1914 Its potential antidiabetic bioactivities 1875:1914 Its potential antidiabetic bioactivities may associate with its α-amylase inhibition and gut microbiome modulation ability. 36807912 6 43 theme weight 715:720 arg1 images 756:761 Molecular weight and atomic force microscope (AFM) images 705:761 Molecular weight and atomic force microscope (AFM) images 705:761 Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. 36807912 12 44 theme glucose 1496:1502 arg1 level 1504:1508 Blood glucose level 1490:1508 Blood glucose level during the oral glucose tolerance test (OGTT) 1490:1554 Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. 36807912 4 45 theme saliva 560:565 arg1 digestion 567:575 in vitro saliva digestion 551:575 in vitro saliva digestion 551:575 RESULTS MEP 2 is stable during in vitro saliva digestion but partially degraded during gastric digestion. 36807912 11 46 theme Serum 1434:1438 arg1 concentration 1440:1452 Serum concentration 1434:1452 Serum concentration of HbA1c 1434:1461 Serum concentration of HbA1c was significantly reduced. 36807912 9 47 theme strong 1182:1187 arg1 activities 1237:1246 strong α-amylase and moderate α-glucosidase inhibition activities 1182:1246 strong α-amylase and moderate α-glucosidase inhibition activities 1182:1246 Both MEP 2 and its digested components show strong α-amylase and moderate α-glucosidase inhibition activities, leading us to further investigate its ability to modulate the diabetic symptoms. 36807912 8 48 theme antioxidant 978:988 arg1 ability 990:996 the antioxidant ability 974:996 the antioxidant ability 974:996 After digestion, the antioxidant ability increases as revealed by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. 36807912 2 49 theme esculenta 355:363 arg1 liquor 335:340 the fermentation liquor 318:340 the fermentation liquor of Morchella esculenta 318:363 A purified exopolysaccharide (MEP 2) was extracted and purified from the fermentation liquor of Morchella esculenta. 36807912 6 50 theme smaller 781:787 arg1 chains 789:794 smaller chains 781:794 smaller chains 781:794 Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. 36807912 13 51 theme microbiota 1618:1627 arg1 diversity 1601:1609 the diversity 1597:1609 the diversity of gut microbiota 1597:1627 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 15 52 theme microbiome 1968:1977 arg1 ability 1990:1996 gut microbiome modulation ability 1964:1996 gut microbiome modulation ability 1964:1996 Its potential antidiabetic bioactivities may associate with its α-amylase inhibition and gut microbiome modulation ability. 36807912 5 53 theme digest 630:635 arg1 enzymes 637:643 The digest enzymes 626:643 The digest enzymes 626:643 The digest enzymes exert negligible effect on the chemical structure of MEP 2. 36807912 9 54 theme α-glucosidase 1212:1224 arg1 activities 1237:1246 strong α-amylase and moderate α-glucosidase inhibition activities 1182:1246 strong α-amylase and moderate α-glucosidase inhibition activities 1182:1246 Both MEP 2 and its digested components show strong α-amylase and moderate α-glucosidase inhibition activities, leading us to further investigate its ability to modulate the diabetic symptoms. 36807912 2 55 theme fermentation 322:333 arg1 liquor 335:340 the fermentation liquor 318:340 the fermentation liquor of Morchella esculenta 318:363 A purified exopolysaccharide (MEP 2) was extracted and purified from the fermentation liquor of Morchella esculenta. 36807912 7 56 theme electron 844:851 arg1 SEM 865:867 SEM 865:867 SEM 865:867 Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. 36807912 7 56 theme electron 844:851 arg1 microscope 853:862 Scanning electron microscope 835:862 Scanning electron microscope (SEM) images 835:875 Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. 36807912 5 57 theme MEP 698:700 arg1 structure 685:693 the chemical structure 672:693 the chemical structure of MEP 2 672:702 The digest enzymes exert negligible effect on the chemical structure of MEP 2. 36807912 10 58 theme inlets 1426:1431 arg1 size 1409:1412 the size 1405:1412 the size of pancreas inlets 1405:1431 MEP 2 treatment ameliorate the inflammatory cell infiltration and increase the size of pancreas inlets. 36807912 1 59 theme important 201:209 arg1 nutraceuticals 211:224 important nutraceuticals 201:224 important nutraceuticals for food applications 201:246 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 1 59 theme important 201:209 arg1 polysaccharides 170:184 BACKGROUND Novel functional polysaccharides 142:184 BACKGROUND Novel functional polysaccharides from fungi 142:195 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 15 60 theme α-amylase 1939:1947 arg1 inhibition 1949:1958 its α-amylase inhibition 1935:1958 its α-amylase inhibition 1935:1958 Its potential antidiabetic bioactivities may associate with its α-amylase inhibition and gut microbiome modulation ability. 36807912 2 61 theme purified 251:258 arg1 MEP 279:281 MEP 2 279:283 MEP 2 279:283 A purified exopolysaccharide (MEP 2) was extracted and purified from the fermentation liquor of Morchella esculenta. 36807912 2 61 theme purified 251:258 arg1 exopolysaccharide 260:276 A purified exopolysaccharide 249:276 A purified exopolysaccharide (MEP 2) 249:284 A purified exopolysaccharide (MEP 2) was extracted and purified from the fermentation liquor of Morchella esculenta. 36807912 13 62 theme several 1771:1777 arg1 species 1795:1801 several Lachnospiraceae species 1771:1801 several Lachnospiraceae species 1771:1801 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 9 63 theme diabetic 1311:1318 arg1 symptoms 1320:1327 the diabetic symptoms 1307:1327 the diabetic symptoms 1307:1327 Both MEP 2 and its digested components show strong α-amylase and moderate α-glucosidase inhibition activities, leading us to further investigate its ability to modulate the diabetic symptoms. 36807912 14 64 dep in 1855:1856 arg1 vitro 1858:1862 vitro 1858:1862 vitro 1858:1862 CONCLUSION MEP 2 was partially degraded during the in vitro digestion. 36807912 0 65 theme esculenta 70:78 arg1 exopolysaccharide 80:96 Morchella esculenta exopolysaccharide 60:96 Morchella esculenta exopolysaccharide 60:96 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 1 66 theme Novel 153:157 arg1 nutraceuticals 211:224 important nutraceuticals 201:224 important nutraceuticals for food applications 201:246 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 1 66 theme Novel 153:157 arg1 polysaccharides 170:184 BACKGROUND Novel functional polysaccharides 142:184 BACKGROUND Novel functional polysaccharides from fungi 142:195 BACKGROUND Novel functional polysaccharides from fungi are important nutraceuticals for food applications. 36807912 3 67 from profile 421:427 arg1 composition 481:491 the microbiota composition 466:491 the microbiota composition in diabetic mice of MEP 2 466:517 The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2. 36807912 6 68 theme Molecular 705:713 arg1 weight 715:720 Molecular weight 705:720 Molecular weight 705:720 Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. 36807912 4 69 dep in 551:552 arg1 vitro 554:558 vitro 554:558 vitro 554:558 RESULTS MEP 2 is stable during in vitro saliva digestion but partially degraded during gastric digestion. 36807912 8 70 theme 2,2'-azino-bis 1068:1081 arg1 assay 1131:1135 the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay 1023:1135 the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay 1023:1135 After digestion, the antioxidant ability increases as revealed by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. 36807912 3 71 theme antioxidant 430:440 arg1 abilities 442:450 antioxidant abilities 430:450 antioxidant abilities 430:450 The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2. 36807912 14 72 theme in 1855:1856 arg1 digestion 1864:1872 the in vitro digestion 1851:1872 the in vitro digestion 1851:1872 CONCLUSION MEP 2 was partially degraded during the in vitro digestion. 36807912 8 73 theme 3-ethylbenzothiazoline-6-sulfonic 1084:1116 arg1 acid 1118:1121 3-ethylbenzothiazoline-6-sulfonic acid 1084:1121 3-ethylbenzothiazoline-6-sulfonic acid 1084:1121 After digestion, the antioxidant ability increases as revealed by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. 36807912 8 73 theme 3-ethylbenzothiazoline-6-sulfonic 1084:1116 arg1 2,2'-azino-bis 1068:1081 2,2'-azino-bis 1068:1081 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) 1068:1122 After digestion, the antioxidant ability increases as revealed by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. 36807912 3 74 theme study 382:386 arg1 aim 370:372 The aim 366:372 The aim of this study 366:386 The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2. 36807912 13 75 theme important 1667:1675 arg1 species 1795:1801 several Lachnospiraceae species 1771:1801 several Lachnospiraceae species 1771:1801 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 13 75 theme important 1667:1675 arg1 Alcaligenaceae 1696:1709 Alcaligenaceae 1696:1709 Alcaligenaceae 1696:1709 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 13 75 theme important 1667:1675 arg1 bacteria 1677:1684 several important bacteria 1659:1684 several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species 1659:1801 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 13 75 theme important 1667:1675 arg1 Demequina 1757:1765 Demequina 1757:1765 Demequina 1757:1765 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 13 75 theme important 1667:1675 arg1 Prevotella 1730:1739 Prevotella 1730:1739 Prevotella 1730:1739 MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species. 36807912 3 76 theme microbiota 470:479 arg1 composition 481:491 the microbiota composition 466:491 the microbiota composition in diabetic mice of MEP 2 466:517 The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2. 36807912 0 77 theme antidiabetic 35:46 arg1 capacity 48:55 antidiabetic capacity 35:55 antidiabetic capacity 35:55 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 12 78 theme glucose 1526:1532 arg1 OGTT 1550:1553 OGTT 1550:1553 OGTT 1550:1553 Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. 36807912 12 78 theme glucose 1526:1532 arg1 test 1544:1547 the oral glucose tolerance test 1517:1547 the oral glucose tolerance test (OGTT) 1517:1554 Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. 36807912 3 79 from effect 456:461 arg1 composition 481:491 the microbiota composition 466:491 the microbiota composition in diabetic mice of MEP 2 466:517 The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2. 36807912 2 80 theme Morchella 345:353 arg1 esculenta 355:363 Morchella esculenta 345:363 Morchella esculenta 345:363 A purified exopolysaccharide (MEP 2) was extracted and purified from the fermentation liquor of Morchella esculenta. 36807912 7 81 theme surface 893:899 arg1 morphology 901:910 the surface morphology 889:910 the surface morphology 889:910 Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. 36807912 3 82 from abilities 442:450 arg1 composition 481:491 the microbiota composition 466:491 the microbiota composition in diabetic mice of MEP 2 466:517 The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2. 36807912 6 83 theme force 733:737 arg1 AFM 751:753 AFM 751:753 AFM 751:753 Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. 36807912 6 83 theme force 733:737 arg1 microscope 739:748 atomic force microscope 726:748 atomic force microscope (AFM) 726:754 Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. 36807912 14 84 theme CONCLUSION 1804:1813 arg1 MEP 1815:1817 CONCLUSION MEP 2 1804:1819 CONCLUSION MEP 2 1804:1819 CONCLUSION MEP 2 was partially degraded during the in vitro digestion. 36807912 0 85 dep profile 10:16 arg1 vitro 102:106 in vitro 99:106 in vitro 99:106 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 0 85 dep profile 10:16 arg1 vivo 112:115 in vivo 109:115 in vivo 109:115 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 0 85 dep profile 10:16 arg1 analysis 132:139 microbiota analysis 121:139 microbiota analysis 121:139 Digestion profile, antioxidant and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis. 36807912 9 86 theme digested 1157:1164 arg1 components 1166:1175 its digested components 1153:1175 its digested components 1153:1175 Both MEP 2 and its digested components show strong α-amylase and moderate α-glucosidase inhibition activities, leading us to further investigate its ability to modulate the diabetic symptoms. 36105478 2 0 dep Cr 450:451 arg1 ions 458:461 ions 458:461 Cr (VI) ions 450:461 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 2 0 dep Cr 450:451 arg1 VI 454:455 VI 454:455 VI 454:455 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 3 1 theme Cr 867:868 arg1 ions 876:879 Cr (III) ions 867:879 Cr (III) ions 867:879 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 2 2 from surface 313:319 arg1 adsorption 279:288 the adsorption 275:288 the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells 275:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 8 3 theme 18.215 1469:1474 arg1 L/mg 1476:1479 18.215 L/mg 1469:1479 18.215 L/mg 1469:1479 Whereas, according to the Temkin model, the constant A was equal to 18.215 L/mg, and bT was equal to 0.023 kJ/mol. 36105478 3 4 theme coordination 884:895 arg1 bonds 897:901 coordination bonds 884:901 coordination bonds with amine and carboxyl groups of algae cells 884:947 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 9 5 theme non-covalent 1612:1623 arg1 interactions 1625:1636 non-covalent interactions 1612:1636 non-covalent interactions 1612:1636 Taking into account the low values of free energy, it is concluded that adsorption is caused by non-covalent interactions. 36105478 10 6 theme model 1826:1830 arg1 framework 1789:1797 the framework 1785:1797 the framework of the pseudo-second order model 1785:1830 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 7 7 from equal 1349:1353 arg1 model 1280:1284 the Dubinin-Radushkevich model 1255:1284 the Dubinin-Radushkevich model 1255:1284 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 3 8 theme cell 747:750 arg1 surface 752:758 the cell surface 743:758 the cell surface 743:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 9 theme degree 555:560 arg1 values 541:546 The highest values 529:546 The highest values of the degree of removal of Cr 529:577 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 13 10 theme temperature 2255:2265 arg1 range 2267:2271 the temperature range 2251:2271 the temperature range of 298-353 K 2251:2284 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 3 11 theme ions 876:879 arg1 formation 854:862 the formation 850:862 the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells 850:947 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 8 12 dep equal 1460:1464 arg1 Whereas 1401:1407 Whereas 1401:1407 Whereas 1401:1407 Whereas, according to the Temkin model, the constant A was equal to 18.215 L/mg, and bT was equal to 0.023 kJ/mol. 36105478 8 12 dep equal 1460:1464 arg1 equal 1460:1464 equal 1460:1464 equal 1460:1464 Whereas, according to the Temkin model, the constant A was equal to 18.215 L/mg, and bT was equal to 0.023 kJ/mol. 36105478 8 12 dep equal 1460:1464 arg1 A 1454:1454 the constant A 1441:1454 the constant A 1441:1454 Whereas, according to the Temkin model, the constant A was equal to 18.215 L/mg, and bT was equal to 0.023 kJ/mol. 36105478 10 13 from surface 1722:1728 arg1 adsorption 1688:1697 the adsorption 1684:1697 the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells 1684:1767 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 5 14 theme maximum 1093:1099 arg1 adsorption 1110:1119 maximum Langmuir adsorption 1093:1119 the maximum Langmuir adsorption value 1089:1125 It was shown that the maximum Langmuir adsorption value was 74.63 mg/g. 36105478 13 15 theme part 2375:2378 arg1 blocking 2361:2368 the blocking 2357:2368 the blocking of a part of the anionic groups on the surface of algae cells 2357:2430 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 3 16 theme Cr 576:577 arg1 removal 565:571 removal 565:571 removal of Cr 565:577 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 5 17 theme adsorption 1110:1119 arg1 value 1121:1125 the maximum Langmuir adsorption value 1089:1125 the maximum Langmuir adsorption value 1089:1125 It was shown that the maximum Langmuir adsorption value was 74.63 mg/g. 36105478 5 17 theme adsorption 1110:1119 arg1 mg/g 1137:1140 74.63 mg/g 1131:1140 74.63 mg/g 1131:1140 It was shown that the maximum Langmuir adsorption value was 74.63 mg/g. 36105478 6 18 theme Freundlich 1200:1209 arg1 model 1211:1215 the Freundlich model 1196:1215 the Freundlich model 1196:1215 The values of the adsorption parameters 1/n and K in the Freundlich model were equal to 0.713 and 2.82 mg/g. 36105478 12 19 theme macromolecules 2120:2133 arg1 polysaccharides 2139:2153 polysaccharides 2139:2153 polysaccharides 2139:2153 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 12 19 theme macromolecules 2120:2133 arg1 sites 2103:2107 nonpolar sites 2094:2107 nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells 2094:2187 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 12 19 theme macromolecules 2120:2133 arg1 macromolecules 2120:2133 protein macromolecules 2112:2133 protein macromolecules 2112:2133 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 3 20 theme removal 565:571 arg1 degree 555:560 the degree 551:560 the degree of removal of Cr 551:577 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 0 21 theme algae 86:90 arg1 cells 92:96 Chlorella vulgaris ZBS1 algae cells 62:96 Chlorella vulgaris ZBS1 algae cells 62:96 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 36105478 3 22 theme groups 706:711 arg1 attraction 684:693 the electrostatic attraction 666:693 the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface 666:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 23 theme algae 937:941 arg1 cells 943:947 algae cells 937:947 algae cells 937:947 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 9 24 theme low 1540:1542 arg1 values 1544:1549 the low values 1536:1549 the low values of free energy 1536:1564 Taking into account the low values of free energy, it is concluded that adsorption is caused by non-covalent interactions. 36105478 4 25 theme models 1063:1068 arg1 framework 996:1004 the framework 992:1004 the framework of Langmuir, Freundlich, Dubinin-Radushkevich and Temkin models 992:1068 The adsorption data were processed within the framework of Langmuir, Freundlich, Dubinin-Radushkevich and Temkin models. 36105478 14 26 theme electrostatic 2464:2476 arg1 repulsion 2478:2486 the electrostatic repulsion 2460:2486 the electrostatic repulsion between the negatively charged surface of the adsorbent and Cr (VI) oxyanions 2460:2564 Therefore, the decrease in the electrostatic repulsion between the negatively charged surface of the adsorbent and Cr (VI) oxyanions is observed. 36105478 12 27 from sites 2103:2107 arg1 composition 2162:2172 the composition 2158:2172 the composition of algae cells 2158:2187 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 7 28 theme maximum 1291:1297 arg1 capacity 1310:1317 the maximum adsorption capacity 1287:1317 the maximum adsorption capacity (qm) 1287:1322 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 7 28 theme maximum 1291:1297 arg1 equal 1349:1353 equal 1349:1353 equal 1349:1353 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 7 28 theme maximum 1291:1297 arg1 qm 1320:1321 qm 1320:1321 qm 1320:1321 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 2 29 theme Cr 450:451 arg1 removal 439:445 removal 439:445 removal of Cr (VI) ions from solutions 439:476 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 2 30 from effect 391:396 arg1 potential 494:502 the zeta potential 485:502 the zeta potential of the cell surface was 485:526 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 2 30 from effect 391:396 arg1 degree 429:434 the degree 425:434 the degree of removal of Cr (VI) ions from solutions 425:476 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 13 31 theme groups 2395:2400 arg1 part 2375:2378 a part 2373:2378 a part of the anionic groups 2373:2400 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 3 32 dep achieved 613:620 arg1 ions 584:587 ions 584:587 ions 584:587 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 32 dep achieved 613:620 arg1 VI 580:581 VI 580:581 VI 580:581 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 33 theme 1-2 641:643 arg1 range 632:636 the pH range 625:636 the pH range of 1-2 625:643 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 2 34 theme removal 439:445 arg1 degree 429:434 the degree 425:434 the degree of removal of Cr (VI) ions from solutions 425:476 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 9 35 theme energy 1559:1564 arg1 values 1544:1549 the low values 1536:1549 the low values of free energy 1536:1564 Taking into account the low values of free energy, it is concluded that adsorption is caused by non-covalent interactions. 36105478 7 36 theme Dubinin-Radushkevich 1259:1278 arg1 model 1280:1284 the Dubinin-Radushkevich model 1255:1284 the Dubinin-Radushkevich model 1255:1284 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 10 37 theme kinetics 1663:1670 arg1 study 1643:1647 The study 1639:1647 The study of adsorption kinetics 1639:1670 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 10 38 theme algae 1757:1761 arg1 cells 1763:1767 Chlorella vulgaris ZBS1 algae cells 1733:1767 Chlorella vulgaris ZBS1 algae cells 1733:1767 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 14 39 theme adsorbent 2534:2542 arg1 oxyanions 2556:2564 oxyanions 2556:2564 the adsorbent and Cr (VI) oxyanions 2530:2564 Therefore, the decrease in the electrostatic repulsion between the negatively charged surface of the adsorbent and Cr (VI) oxyanions is observed. 36105478 8 40 theme Temkin 1427:1432 arg1 model 1434:1438 the Temkin model 1423:1438 the Temkin model 1423:1438 Whereas, according to the Temkin model, the constant A was equal to 18.215 L/mg, and bT was equal to 0.023 kJ/mol. 36105478 7 41 theme 39.73 1358:1362 arg1 mg/g 1364:1367 39.73 mg/g 1358:1367 39.73 mg/g 1358:1367 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 12 42 theme algae 2177:2181 arg1 cells 2183:2187 algae cells 2177:2187 algae cells 2177:2187 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 0 43 from Peculiarities 0:12 arg1 surface 51:57 the surface 47:57 the surface of Chlorella vulgaris ZBS1 algae cells 47:96 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 36105478 11 44 theme models 1919:1924 arg1 framework 1889:1897 the framework 1885:1897 the framework of the IPDM and ELM models 1885:1924 The kinetic behavior of the process is discussed in the framework of the IPDM and ELM models. 36105478 14 45 theme charged 2511:2517 arg1 surface 2519:2525 the negatively charged surface 2496:2525 the negatively charged surface of the adsorbent and Cr (VI) oxyanions 2496:2564 Therefore, the decrease in the electrostatic repulsion between the negatively charged surface of the adsorbent and Cr (VI) oxyanions is observed. 36105478 12 46 dep Cr 1999:2000 arg1 ions 2007:2010 ions 2007:2010 Cr (VI) ions 1999:2010 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 12 46 dep Cr 1999:2000 arg1 VI 2003:2004 VI 2003:2004 VI 2003:2004 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 8 47 theme constant 1445:1452 arg1 Whereas 1401:1407 Whereas 1401:1407 Whereas 1401:1407 Whereas, according to the Temkin model, the constant A was equal to 18.215 L/mg, and bT was equal to 0.023 kJ/mol. 36105478 8 47 theme constant 1445:1452 arg1 equal 1460:1464 equal 1460:1464 equal 1460:1464 Whereas, according to the Temkin model, the constant A was equal to 18.215 L/mg, and bT was equal to 0.023 kJ/mol. 36105478 8 47 theme constant 1445:1452 arg1 A 1454:1454 the constant A 1441:1454 the constant A 1441:1454 Whereas, according to the Temkin model, the constant A was equal to 18.215 L/mg, and bT was equal to 0.023 kJ/mol. 36105478 10 48 dep Chlorella 1733:1741 arg1 vulgaris 1743:1750 vulgaris 1743:1750 vulgaris 1743:1750 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 3 49 theme attraction 684:693 arg1 result 656:661 the result 652:661 the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface 652:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 49 theme attraction 684:693 arg1 possibility 768:778 the possibility 764:778 the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells 764:947 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 2 50 theme pH 405:406 arg1 effect 391:396 the effect 387:396 the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was 387:526 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 2 51 dep Cr 293:294 arg1 ions 301:304 ions 301:304 Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells 293:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 2 51 dep Cr 293:294 arg1 VI 297:298 VI 297:298 VI 297:298 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 0 52 theme vulgaris 72:79 arg1 cells 92:96 Chlorella vulgaris ZBS1 algae cells 62:96 Chlorella vulgaris ZBS1 algae cells 62:96 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 36105478 2 53 dep Chlorella 324:332 arg1 vulgaris 334:341 vulgaris 334:341 vulgaris 334:341 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 2 54 theme algae 348:352 arg1 cells 354:358 Chlorella vulgaris ZBS1 algae cells 324:358 Chlorella vulgaris ZBS1 algae cells 324:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 2 55 theme surface 516:522 arg1 potential 494:502 the zeta potential 485:502 the zeta potential of the cell surface was 485:526 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 7 56 theme free 1328:1331 arg1 E 1341:1341 E 1341:1341 E 1341:1341 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 7 56 theme free 1328:1331 arg1 energy 1333:1338 free energy 1328:1338 free energy (E) 1328:1342 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 12 57 theme intraparticle 1972:1984 arg1 diffusion 1986:1994 intraparticle diffusion 1972:1994 intraparticle diffusion of Cr (VI) ions 1972:2010 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 12 58 theme protein 2112:2118 arg1 macromolecules 2120:2133 protein macromolecules 2112:2133 protein macromolecules 2112:2133 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 0 59 theme adsorption 17:26 arg1 Peculiarities 0:12 Peculiarities 0:12 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 0:97 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 36105478 1 60 theme features 219:226 arg1 study 193:197 the study 189:197 the study of their adsorption features 189:226 Cr (VI) compounds are the most dangerous for human health and the environment, therefore, the study of their adsorption features is of great interest. 36105478 13 61 theme volume 2334:2339 arg1 shrinkage 2306:2314 the shrinkage 2302:2314 the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells 2302:2430 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 13 62 theme algae 2420:2424 arg1 cells 2426:2430 algae cells 2420:2430 algae cells 2420:2430 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 3 63 theme HCrO4 698:702 arg1 attraction 684:693 the electrostatic attraction 666:693 the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface 666:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 10 64 theme Cr 1702:1703 arg1 adsorption 1688:1697 the adsorption 1684:1697 the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells 1684:1767 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 0 65 theme Cr 31:32 arg1 adsorption 17:26 adsorption 17:26 adsorption of Cr (VI) ions 17:42 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 36105478 13 66 from increase 2194:2201 arg1 range 2267:2271 the temperature range 2251:2271 the temperature range of 298-353 K 2251:2284 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 13 66 from increase 2194:2201 arg1 adsorption 2210:2219 the adsorption 2206:2219 the adsorption of Cr (VI) ions at pH 8.62 2206:2246 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 3 67 with bonds 897:901 arg1 groups 927:932 amine and carboxyl groups 908:932 groups 927:932 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 67 with bonds 897:901 arg1 cells 943:947 algae cells 937:947 algae cells 937:947 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 68 theme protonated 716:725 arg1 groups 733:738 protonated amino groups 716:738 protonated amino groups of the cell surface 716:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 68 theme protonated 716:725 arg1 surface 752:758 the cell surface 743:758 the cell surface 743:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 10 69 theme adsorption 1652:1661 arg1 kinetics 1663:1670 adsorption kinetics 1652:1670 adsorption kinetics 1652:1670 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 2 70 theme comprehensive 252:264 arg1 study 266:270 A comprehensive study 250:270 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells 250:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 12 71 theme cells 2183:2187 arg1 composition 2162:2172 the composition 2158:2172 the composition of algae cells 2158:2187 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 6 72 dep parameters 1172:1181 arg1 parameters 1172:1181 the adsorption parameters 1/n and K 1157:1191 the adsorption parameters 1/n and K 1157:1191 The values of the adsorption parameters 1/n and K in the Freundlich model were equal to 0.713 and 2.82 mg/g. 36105478 6 72 dep parameters 1172:1181 arg1 K 1191:1191 K 1191:1191 K 1191:1191 The values of the adsorption parameters 1/n and K in the Freundlich model were equal to 0.713 and 2.82 mg/g. 36105478 6 72 dep parameters 1172:1181 arg1 1/n 1183:1185 1/n 1183:1185 1/n 1183:1185 The values of the adsorption parameters 1/n and K in the Freundlich model were equal to 0.713 and 2.82 mg/g. 36105478 11 73 theme process 1861:1867 arg1 behavior 1845:1852 The kinetic behavior 1833:1852 The kinetic behavior of the process 1833:1867 The kinetic behavior of the process is discussed in the framework of the IPDM and ELM models. 36105478 4 74 theme adsorption 954:963 arg1 data 965:968 The adsorption data 950:968 The adsorption data 950:968 The adsorption data were processed within the framework of Langmuir, Freundlich, Dubinin-Radushkevich and Temkin models. 36105478 2 75 theme Cr 293:294 arg1 adsorption 279:288 the adsorption 275:288 the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells 275:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 6 76 theme adsorption 1161:1170 arg1 parameters 1172:1181 the adsorption parameters 1/n and K 1157:1191 the adsorption parameters 1/n and K 1157:1191 The values of the adsorption parameters 1/n and K in the Freundlich model were equal to 0.713 and 2.82 mg/g. 36105478 6 76 theme adsorption 1161:1170 arg1 K 1191:1191 K 1191:1191 K 1191:1191 The values of the adsorption parameters 1/n and K in the Freundlich model were equal to 0.713 and 2.82 mg/g. 36105478 6 76 theme adsorption 1161:1170 arg1 1/n 1183:1185 1/n 1183:1185 1/n 1183:1185 The values of the adsorption parameters 1/n and K in the Freundlich model were equal to 0.713 and 2.82 mg/g. 36105478 2 77 theme adsorption 279:288 arg1 study 266:270 A comprehensive study 250:270 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells 250:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 13 78 theme anionic 2387:2393 arg1 groups 2395:2400 the anionic groups 2383:2400 the anionic groups 2383:2400 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 4 79 theme Dubinin-Radushkevich 1031:1050 arg1 framework 996:1004 the framework 992:1004 the framework of Langmuir, Freundlich, Dubinin-Radushkevich and Temkin models 992:1068 The adsorption data were processed within the framework of Langmuir, Freundlich, Dubinin-Radushkevich and Temkin models. 36105478 3 80 theme bonds 897:901 arg1 formation 854:862 the formation 850:862 the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells 850:947 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 10 81 theme order 1820:1824 arg1 model 1826:1830 the pseudo-second order model 1802:1830 the pseudo-second order model 1802:1830 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 2 82 from adsorption 279:288 arg1 surface 313:319 the surface 309:319 the surface of Chlorella vulgaris ZBS1 algae cells 309:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 13 83 from pH 2240:2241 arg1 Cr 2224:2225 Cr (VI) ions at pH 8.62 2224:2246 Cr (VI) ions at pH 8.62 2224:2246 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 13 83 from pH 2240:2241 arg1 adsorption 2210:2219 the adsorption 2206:2219 the adsorption of Cr (VI) ions at pH 8.62 2206:2246 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 4 84 theme Langmuir 1009:1016 arg1 framework 996:1004 the framework 992:1004 the framework of Langmuir, Freundlich, Dubinin-Radushkevich and Temkin models 992:1068 The adsorption data were processed within the framework of Langmuir, Freundlich, Dubinin-Radushkevich and Temkin models. 36105478 5 85 theme Langmuir 1101:1108 arg1 adsorption 1110:1119 maximum Langmuir adsorption 1093:1119 the maximum Langmuir adsorption value 1089:1125 It was shown that the maximum Langmuir adsorption value was 74.63 mg/g. 36105478 14 86 theme oxyanions 2556:2564 arg1 surface 2519:2525 the negatively charged surface 2496:2525 the negatively charged surface of the adsorbent and Cr (VI) oxyanions 2496:2564 Therefore, the decrease in the electrostatic repulsion between the negatively charged surface of the adsorbent and Cr (VI) oxyanions is observed. 36105478 3 87 theme carboxyl 918:925 arg1 groups 927:932 amine and carboxyl groups 908:932 groups 927:932 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 87 theme carboxyl 918:925 arg1 cells 943:947 algae cells 937:947 algae cells 937:947 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 2 88 from Cr 293:294 arg1 surface 313:319 the surface 309:319 the surface of Chlorella vulgaris ZBS1 algae cells 309:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 0 89 theme cells 92:96 arg1 surface 51:57 the surface 47:57 the surface of Chlorella vulgaris ZBS1 algae cells 47:96 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 36105478 0 90 dep Cr 31:32 arg1 ions 39:42 ions 39:42 Cr (VI) ions 31:42 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 36105478 0 90 dep Cr 31:32 arg1 VI 35:36 VI 35:36 VI 35:36 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 36105478 12 91 theme polysaccharides 2139:2153 arg1 polysaccharides 2139:2153 polysaccharides 2139:2153 polysaccharides 2139:2153 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 12 91 theme polysaccharides 2139:2153 arg1 sites 2103:2107 nonpolar sites 2094:2107 nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells 2094:2187 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 12 91 theme polysaccharides 2139:2153 arg1 macromolecules 2120:2133 protein macromolecules 2112:2133 protein macromolecules 2112:2133 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 3 92 theme amine 908:912 arg1 groups 927:932 amine and carboxyl groups 908:932 groups 927:932 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 92 theme amine 908:912 arg1 cells 943:947 algae cells 937:947 algae cells 937:947 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 7 93 theme adsorption 1299:1308 arg1 capacity 1310:1317 the maximum adsorption capacity 1287:1317 the maximum adsorption capacity (qm) 1287:1322 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 7 93 theme adsorption 1299:1308 arg1 equal 1349:1353 equal 1349:1353 equal 1349:1353 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 7 93 theme adsorption 1299:1308 arg1 qm 1320:1321 qm 1320:1321 qm 1320:1321 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 11 94 theme kinetic 1837:1843 arg1 behavior 1845:1852 The kinetic behavior 1833:1852 The kinetic behavior of the process 1833:1867 The kinetic behavior of the process is discussed in the framework of the IPDM and ELM models. 36105478 13 95 theme Cr 2224:2225 arg1 adsorption 2210:2219 the adsorption 2206:2219 the adsorption of Cr (VI) ions at pH 8.62 2206:2246 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 3 96 theme cells 943:947 arg1 groups 927:932 amine and carboxyl groups 908:932 groups 927:932 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 96 theme cells 943:947 arg1 cells 943:947 algae cells 937:947 algae cells 937:947 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 2 97 theme medium 415:420 arg1 pH 405:406 the pH 401:406 the pH of the medium 401:420 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 10 98 theme Chlorella 1733:1741 arg1 cells 1763:1767 Chlorella vulgaris ZBS1 algae cells 1733:1767 Chlorella vulgaris ZBS1 algae cells 1733:1767 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 4 99 theme Temkin 1056:1061 arg1 models 1063:1068 Temkin models 1056:1068 Temkin models 1056:1068 The adsorption data were processed within the framework of Langmuir, Freundlich, Dubinin-Radushkevich and Temkin models. 36105478 13 100 from adsorption 2210:2219 arg1 pH 2240:2241 pH 8.62 2240:2246 pH 8.62 2240:2246 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 9 101 theme free 1554:1557 arg1 energy 1559:1564 free energy 1554:1564 free energy 1554:1564 Taking into account the low values of free energy, it is concluded that adsorption is caused by non-covalent interactions. 36105478 10 102 theme cells 1763:1767 arg1 surface 1722:1728 the surface 1718:1728 the surface of Chlorella vulgaris ZBS1 algae cells 1718:1767 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 13 103 theme biosorbent 2323:2332 arg1 volume 2334:2339 the biosorbent volume 2319:2339 the biosorbent volume 2319:2339 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 7 104 theme 2.604 1373:1377 arg1 kJ/mol 1379:1384 2.604 kJ/mol 1373:1384 2.604 kJ/mol 1373:1384 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 10 105 theme ZBS1 1752:1755 arg1 cells 1763:1767 Chlorella vulgaris ZBS1 algae cells 1733:1767 Chlorella vulgaris ZBS1 algae cells 1733:1767 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 7 106 from model 1280:1284 arg1 capacity 1310:1317 the maximum adsorption capacity 1287:1317 the maximum adsorption capacity (qm) 1287:1322 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 7 106 from model 1280:1284 arg1 equal 1349:1353 equal 1349:1353 equal 1349:1353 In the Dubinin-Radushkevich model, the maximum adsorption capacity (qm) and free energy (E) were equal to 39.73 mg/g and 2.604 kJ/mol, respectively. 36105478 11 107 theme ELM 1915:1917 arg1 models 1919:1924 the IPDM and ELM models 1902:1924 models 1919:1924 The kinetic behavior of the process is discussed in the framework of the IPDM and ELM models. 36105478 3 108 theme pH 629:630 arg1 range 632:636 the pH range 625:636 the pH range of 1-2 625:643 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 0 109 theme Chlorella 62:70 arg1 cells 92:96 Chlorella vulgaris ZBS1 algae cells 62:96 Chlorella vulgaris ZBS1 algae cells 62:96 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 36105478 11 110 theme IPDM 1906:1909 arg1 models 1919:1924 the IPDM and ELM models 1902:1924 models 1919:1924 The kinetic behavior of the process is discussed in the framework of the IPDM and ELM models. 36105478 13 111 dep Cr 2224:2225 arg1 VI 2228:2229 VI 2228:2229 VI 2228:2229 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 13 111 dep Cr 2224:2225 arg1 ions 2232:2235 ions 2232:2235 Cr (VI) ions at pH 8.62 2224:2246 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 3 112 theme surface 752:758 arg1 groups 733:738 protonated amino groups 716:738 protonated amino groups of the cell surface 716:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 112 theme surface 752:758 arg1 surface 752:758 the cell surface 743:758 the cell surface 743:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 2 113 theme zeta 489:492 arg1 potential 494:502 the zeta potential 485:502 the zeta potential of the cell surface was 485:526 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 1 114 dep Cr 99:100 arg1 VI 103:104 VI 103:104 VI 103:104 Cr (VI) compounds are the most dangerous for human health and the environment, therefore, the study of their adsorption features is of great interest. 36105478 1 114 dep Cr 99:100 arg1 compounds 107:115 compounds 107:115 Cr (VI) compounds 99:115 Cr (VI) compounds are the most dangerous for human health and the environment, therefore, the study of their adsorption features is of great interest. 36105478 0 115 theme ZBS1 81:84 arg1 cells 92:96 Chlorella vulgaris ZBS1 algae cells 62:96 Chlorella vulgaris ZBS1 algae cells 62:96 Peculiarities of adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells. 36105478 1 116 theme human 144:148 arg1 health 150:155 human health 144:155 human health 144:155 Cr (VI) compounds are the most dangerous for human health and the environment, therefore, the study of their adsorption features is of great interest. 36105478 10 117 dep Cr 1702:1703 arg1 ions 1710:1713 ions 1710:1713 Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells 1702:1767 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 10 117 dep Cr 1702:1703 arg1 VI 1706:1707 VI 1706:1707 VI 1706:1707 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 12 118 theme nonpolar 2094:2101 arg1 polysaccharides 2139:2153 polysaccharides 2139:2153 polysaccharides 2139:2153 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 12 118 theme nonpolar 2094:2101 arg1 sites 2103:2107 nonpolar sites 2094:2107 nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells 2094:2187 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 12 118 theme nonpolar 2094:2101 arg1 macromolecules 2120:2133 protein macromolecules 2112:2133 protein macromolecules 2112:2133 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 10 119 theme pseudo-second 1806:1818 arg1 model 1826:1830 the pseudo-second order model 1802:1830 the pseudo-second order model 1802:1830 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 13 120 theme K 2284:2284 arg1 range 2267:2271 the temperature range 2251:2271 the temperature range of 298-353 K 2251:2284 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 3 121 theme electrostatic 670:682 arg1 attraction 684:693 the electrostatic attraction 666:693 the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface 666:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 2 122 theme ZBS1 343:346 arg1 cells 354:358 Chlorella vulgaris ZBS1 algae cells 324:358 Chlorella vulgaris ZBS1 algae cells 324:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 12 123 theme diffusion 1986:1994 arg1 constant 1960:1967 the constant 1956:1967 the constant of intraparticle diffusion of Cr (VI) ions 1956:2010 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 2 124 theme cell 511:514 arg1 surface 516:522 the cell surface 507:522 the cell surface was 507:526 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 13 125 from blocking 2361:2368 arg1 surface 2409:2415 the surface 2405:2415 the surface of algae cells 2405:2430 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 1 126 theme adsorption 208:217 arg1 features 219:226 their adsorption features 202:226 their adsorption features 202:226 Cr (VI) compounds are the most dangerous for human health and the environment, therefore, the study of their adsorption features is of great interest. 36105478 14 127 dep oxyanions 2556:2564 arg1 VI 2552:2553 VI 2552:2553 VI 2552:2553 Therefore, the decrease in the electrostatic repulsion between the negatively charged surface of the adsorbent and Cr (VI) oxyanions is observed. 36105478 2 128 theme Chlorella 324:332 arg1 cells 354:358 Chlorella vulgaris ZBS1 algae cells 324:358 Chlorella vulgaris ZBS1 algae cells 324:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 12 129 theme Cr 1999:2000 arg1 diffusion 1986:1994 intraparticle diffusion 1972:1994 intraparticle diffusion of Cr (VI) ions 1972:2010 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 14 130 theme Cr 2548:2549 arg1 oxyanions 2556:2564 oxyanions 2556:2564 the adsorbent and Cr (VI) oxyanions 2530:2564 Therefore, the decrease in the electrostatic repulsion between the negatively charged surface of the adsorbent and Cr (VI) oxyanions is observed. 36105478 3 131 theme acidic 823:828 arg1 medium 830:835 an acidic medium 820:835 an acidic medium 820:835 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 13 132 theme cells 2426:2430 arg1 surface 2409:2415 the surface 2405:2415 the surface of algae cells 2405:2430 The increase in the adsorption of Cr (VI) ions at pH 8.62 in the temperature range of 298-353 K is justified by the shrinkage of the biosorbent volume, which leads to the blocking of a part of the anionic groups on the surface of algae cells. 36105478 2 133 from solutions 468:476 arg1 removal 439:445 removal 439:445 removal of Cr (VI) ions from solutions 439:476 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 2 133 from solutions 468:476 arg1 degree 429:434 the degree 425:434 the degree of removal of Cr (VI) ions from solutions 425:476 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 10 134 from adsorption 1688:1697 arg1 surface 1722:1728 the surface 1718:1728 the surface of Chlorella vulgaris ZBS1 algae cells 1718:1767 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 1 135 theme great 234:238 arg1 interest 240:247 great interest 234:247 great interest 234:247 Cr (VI) compounds are the most dangerous for human health and the environment, therefore, the study of their adsorption features is of great interest. 36105478 2 136 theme cells 354:358 arg1 surface 313:319 the surface 309:319 the surface of Chlorella vulgaris ZBS1 algae cells 309:358 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 10 137 from Cr 1702:1703 arg1 surface 1722:1728 the surface 1718:1728 the surface of Chlorella vulgaris ZBS1 algae cells 1718:1767 The study of adsorption kinetics showed that the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells is described in the framework of the pseudo-second order model. 36105478 14 138 from decrease 2448:2455 arg1 repulsion 2478:2486 the electrostatic repulsion 2460:2486 the electrostatic repulsion between the negatively charged surface of the adsorbent and Cr (VI) oxyanions 2460:2564 Therefore, the decrease in the electrostatic repulsion between the negatively charged surface of the adsorbent and Cr (VI) oxyanions is observed. 36105478 6 139 from values 1147:1152 arg1 model 1211:1215 the Freundlich model 1196:1215 the Freundlich model 1196:1215 The values of the adsorption parameters 1/n and K in the Freundlich model were equal to 0.713 and 2.82 mg/g. 36105478 3 140 theme amino 727:731 arg1 groups 733:738 protonated amino groups 716:738 protonated amino groups of the cell surface 716:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 140 theme amino 727:731 arg1 surface 752:758 the cell surface 743:758 the cell surface 743:758 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 12 141 theme hydrophobic 2061:2071 arg1 interactions 2073:2084 hydrophobic interactions 2061:2084 hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells 2061:2187 With increasing temperature, the constant of intraparticle diffusion of Cr (VI) ions decreases, which is explained with increasing of hydrophobic interactions between nonpolar sites of protein macromolecules and polysaccharides in the composition of algae cells. 36105478 6 142 theme parameters 1172:1181 arg1 equal 1222:1226 equal 1222:1226 equal 1222:1226 The values of the adsorption parameters 1/n and K in the Freundlich model were equal to 0.713 and 2.82 mg/g. 36105478 6 142 theme parameters 1172:1181 arg1 values 1147:1152 The values 1143:1152 The values of the adsorption parameters 1/n and K in the Freundlich model 1143:1215 The values of the adsorption parameters 1/n and K in the Freundlich model were equal to 0.713 and 2.82 mg/g. 36105478 2 143 from degree 429:434 arg1 solutions 468:476 solutions 468:476 solutions 468:476 A comprehensive study of the adsorption of Cr (VI) ions on the surface of Chlorella vulgaris ZBS1 algae cells was carried out evaluating the effect of the pH of the medium on the degree of removal of Cr (VI) ions from solutions and on the zeta potential of the cell surface was. 36105478 3 144 theme highest 533:539 arg1 values 541:546 The highest values 529:546 The highest values of the degree of removal of Cr 529:577 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 145 dep Cr 792:793 arg1 ions 800:803 ions 800:803 Cr (VI) ions to Cr (III) 792:815 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 36105478 3 145 dep Cr 792:793 arg1 VI 796:797 VI 796:797 VI 796:797 The highest values of the degree of removal of Cr (VI) ions equal to 94.6-95.4% are achieved in the pH range of 1-2, being the result of the electrostatic attraction of HCrO4 - groups to protonated amino groups of the cell surface and the possibility of reducing Cr (VI) ions to Cr (III) in an acidic medium, followed by the formation of Cr (III) ions of coordination bonds with amine and carboxyl groups of algae cells. 35411374 5 0 theme distinct 735:742 arg1 sites 729:733 sites 729:733 sites distinct from those modified by POGLUT1 729:773 Recently, POGLUT2 and POGLUT3 were identified as two novel O-glucosyltransferases that modify a few Notch EGF repeats at sites distinct from those modified by POGLUT1. 35411374 6 1 theme proteins 912:919 arg1 modification 870:881 modification 870:881 modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs) 870:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 7 2 from repeats 1111:1117 arg1 LTBP1 1122:1126 LTBP1 1122:1126 LTBP1 1122:1126 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 3 from FBN2 1082:1085 arg1 half 1092:1095 half 1092:1095 half of the 18 EGF repeats in LTBP1 1092:1126 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 3 from FBN2 1082:1085 arg1 half 1043:1046 approximately half 1029:1046 approximately half of the 47 EGF repeats in FBN1 and FBN2 1029:1085 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 1 4 theme crucial 143:149 arg1 roles 151:155 crucial roles 143:155 crucial roles 143:155 O-glycosylation of Epidermal Growth Factor-like (EGF) repeats plays crucial roles in protein folding, trafficking and function. 35411374 7 5 from LTBP1 1122:1126 arg1 half 1092:1095 half 1092:1095 half of the 18 EGF repeats in LTBP1 1092:1126 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 5 from LTBP1 1122:1126 arg1 half 1043:1046 approximately half 1029:1046 approximately half of the 47 EGF repeats in FBN1 and FBN2 1029:1085 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 0 6 theme POGLUT3 66:72 arg1 function 16:23 function 16:23 function 16:23 Identification, function, and biological relevance of POGLUT2 and POGLUT3. 35411374 0 6 theme POGLUT3 66:72 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification, function, and biological relevance of POGLUT2 and POGLUT3. 35411374 0 6 theme POGLUT3 66:72 arg1 relevance 41:49 biological relevance 30:49 biological relevance 30:49 Identification, function, and biological relevance of POGLUT2 and POGLUT3. 35411374 5 7 from those 749:753 arg1 distinct 735:742 distinct 735:742 distinct 735:742 Recently, POGLUT2 and POGLUT3 were identified as two novel O-glucosyltransferases that modify a few Notch EGF repeats at sites distinct from those modified by POGLUT1. 35411374 5 8 theme few 704:706 arg1 repeats 718:724 a few Notch EGF repeats 702:724 a few Notch EGF repeats 702:724 Recently, POGLUT2 and POGLUT3 were identified as two novel O-glucosyltransferases that modify a few Notch EGF repeats at sites distinct from those modified by POGLUT1. 35411374 6 9 theme extracellular 891:903 arg1 fibrillins 931:940 fibrillins 931:940 fibrillins (FBNs) 931:947 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 6 9 theme extracellular 891:903 arg1 proteins 912:919 many extracellular matrix proteins 886:919 many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs) 886:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 6 9 theme extracellular 891:903 arg1 proteins 973:980 Latent TGFβ-binding proteins 953:980 Latent TGFβ-binding proteins (LTBPs) 953:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 3 10 theme Specific 500:507 arg1 Domain 493:498 EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT) 489:555 EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT) 489:555 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 7 11 from repeats 1062:1068 arg1 FBN2 1082:1085 FBN2 1082:1085 FBN2 1082:1085 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 11 from repeats 1062:1068 arg1 FBN1 1073:1076 FBN1 1073:1076 FBN1 1073:1076 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 1 12 gly O-glycosylation 75:89 arg1 repeats 129:135 Epidermal Growth Factor-like (EGF) repeats 94:135 Epidermal Growth Factor-like (EGF) repeats 94:135 O-glycosylation of Epidermal Growth Factor-like (EGF) repeats plays crucial roles in protein folding, trafficking and function. 35411374 6 13 theme many 886:889 arg1 fibrillins 931:940 fibrillins 931:940 fibrillins (FBNs) 931:947 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 6 13 theme many 886:889 arg1 proteins 912:919 many extracellular matrix proteins 886:919 many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs) 886:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 6 13 theme many 886:889 arg1 proteins 973:980 Latent TGFβ-binding proteins 953:980 Latent TGFβ-binding proteins (LTBPs) 953:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 7 14 theme repeats 1111:1117 arg1 half 1092:1095 half 1092:1095 half of the 18 EGF repeats in LTBP1 1092:1126 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 14 theme repeats 1111:1117 arg1 half 1043:1046 approximately half 1029:1046 approximately half of the 47 EGF repeats in FBN1 and FBN2 1029:1085 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 3 15 theme O-Linked 509:516 arg1 Transferase 538:548 O-Linked N-Acetylglucosamine Transferase 509:548 EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT) 489:555 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 3 15 theme O-Linked 509:516 arg1 EOGT 551:554 EOGT 551:554 EOGT 551:554 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 9 16 theme protein-protein 1334:1348 arg1 interactions 1350:1361 protein-protein interactions 1334:1361 protein-protein interactions 1334:1361 There is precedent for EGF modifications to affect protein-protein interactions, as has been demonstrated by research of POGLUT1 and POFUT1 modifications on Notch. 35411374 9 17 theme POGLUT1 1404:1410 arg1 modifications 1423:1435 POGLUT1 and POFUT1 modifications 1404:1435 POGLUT1 and POFUT1 modifications 1404:1435 There is precedent for EGF modifications to affect protein-protein interactions, as has been demonstrated by research of POGLUT1 and POFUT1 modifications on Notch. 35411374 5 18 theme EGF 714:716 arg1 repeats 718:724 a few Notch EGF repeats 702:724 a few Notch EGF repeats 702:724 Recently, POGLUT2 and POGLUT3 were identified as two novel O-glucosyltransferases that modify a few Notch EGF repeats at sites distinct from those modified by POGLUT1. 35411374 2 19 theme EGF 316:318 arg1 repeats 320:326 its many O-glycosylated EGF repeats 292:326 its many O-glycosylated EGF repeats 292:326 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 3 20 theme EGF 489:491 arg1 Domain 493:498 EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT) 489:555 EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT) 489:555 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 9 21 theme modifications 1423:1435 arg1 research 1392:1399 research 1392:1399 research of POGLUT1 and POFUT1 modifications on Notch 1392:1444 There is precedent for EGF modifications to affect protein-protein interactions, as has been demonstrated by research of POGLUT1 and POFUT1 modifications on Notch. 35411374 7 22 theme EGF 1107:1109 arg1 repeats 1111:1117 the 18 EGF repeats 1100:1117 the 18 EGF repeats in LTBP1 1100:1126 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 0 23 theme biological 30:39 arg1 relevance 41:49 biological relevance 30:49 biological relevance 30:49 Identification, function, and biological relevance of POGLUT2 and POGLUT3. 35411374 7 24 from half 1043:1046 arg1 FBN2 1082:1085 FBN2 1082:1085 FBN2 1082:1085 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 24 from half 1043:1046 arg1 FBN1 1073:1076 FBN1 1073:1076 FBN1 1073:1076 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 24 from half 1043:1046 arg1 LTBP1 1122:1126 LTBP1 1122:1126 LTBP1 1122:1126 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 2 25 used used 243:246 arg2 domain 227:232 The Notch extracellular domain 203:232 The Notch extracellular domain 203:232 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 2 25 used used 243:246 arg2 model 253:257 a model 251:257 a model to study these mechanisms due to its many O-glycosylated EGF repeats 251:326 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 1 26 theme protein 160:166 arg1 folding 168:174 protein folding 160:174 protein folding 160:174 O-glycosylation of Epidermal Growth Factor-like (EGF) repeats plays crucial roles in protein folding, trafficking and function. 35411374 10 27 theme POGLUT3 1518:1524 arg1 identification 1467:1480 identification 1467:1480 identification 1467:1480 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 10 27 theme POGLUT3 1518:1524 arg1 research 1542:1549 the ongoing research 1530:1549 the ongoing research that continues to elucidate the biological significance of these novel enzymes 1530:1628 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 10 27 theme POGLUT3 1518:1524 arg1 characterization 1486:1501 characterization 1486:1501 characterization 1486:1501 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 10 28 theme biological 1583:1592 arg1 significance 1594:1605 the biological significance 1579:1605 the biological significance of these novel enzymes 1579:1628 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 10 29 theme POGLUT2 1506:1512 arg1 identification 1467:1480 identification 1467:1480 identification 1467:1480 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 10 29 theme POGLUT2 1506:1512 arg1 research 1542:1549 the ongoing research 1530:1549 the ongoing research that continues to elucidate the biological significance of these novel enzymes 1530:1628 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 10 29 theme POGLUT2 1506:1512 arg1 characterization 1486:1501 characterization 1486:1501 characterization 1486:1501 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 8 30 theme modifications 1205:1217 arg1 loss 1197:1200 loss 1197:1200 loss of modifications by POGLUT2 and/or POGLUT3 1197:1243 Cellular assays showed that loss of modifications by POGLUT2 and/or POGLUT3 significantly reduces FBN1 secretion. 35411374 6 31 theme matrix 905:910 arg1 fibrillins 931:940 fibrillins 931:940 fibrillins (FBNs) 931:947 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 6 31 theme matrix 905:910 arg1 proteins 912:919 many extracellular matrix proteins 886:919 many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs) 886:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 6 31 theme matrix 905:910 arg1 proteins 973:980 Latent TGFβ-binding proteins 953:980 Latent TGFβ-binding proteins (LTBPs) 953:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 7 32 from FBN1 1073:1076 arg1 half 1092:1095 half 1092:1095 half of the 18 EGF repeats in LTBP1 1092:1126 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 32 from FBN1 1073:1076 arg1 half 1043:1046 approximately half 1029:1046 approximately half of the 47 EGF repeats in FBN1 and FBN2 1029:1085 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 8 33 theme Cellular 1169:1176 arg1 assays 1178:1183 Cellular assays 1169:1183 Cellular assays 1169:1183 Cellular assays showed that loss of modifications by POGLUT2 and/or POGLUT3 significantly reduces FBN1 secretion. 35411374 2 34 theme due 285:287 arg1 mechanisms 274:283 these mechanisms 268:283 these mechanisms due to its many O-glycosylated EGF repeats 268:326 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 3 35 theme Protein 401:407 arg1 O-Glucosyltransferase 409:429 Protein O-Glucosyltransferase 1 401:431 Protein O-Glucosyltransferase 1 (POGLUT1) 401:441 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 3 35 theme Protein 401:407 arg1 POGLUT1 434:440 POGLUT1 434:440 POGLUT1 434:440 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 6 36 theme TGFβ-binding 960:971 arg1 LTBPs 983:987 LTBPs 983:987 LTBPs 983:987 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 6 36 theme TGFβ-binding 960:971 arg1 proteins 973:980 Latent TGFβ-binding proteins 953:980 Latent TGFβ-binding proteins (LTBPs) 953:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 7 37 theme repeats 1062:1068 arg1 half 1092:1095 half 1092:1095 half of the 18 EGF repeats in LTBP1 1092:1126 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 37 theme repeats 1062:1068 arg1 half 1043:1046 approximately half 1029:1046 approximately half of the 47 EGF repeats in FBN1 and FBN2 1029:1085 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 1 38 theme Epidermal 94:102 arg1 repeats 129:135 Epidermal Growth Factor-like (EGF) repeats 94:135 Epidermal Growth Factor-like (EGF) repeats 94:135 O-glycosylation of Epidermal Growth Factor-like (EGF) repeats plays crucial roles in protein folding, trafficking and function. 35411374 6 39 theme Latent 953:958 arg1 LTBPs 983:987 LTBPs 983:987 LTBPs 983:987 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 6 39 theme Latent 953:958 arg1 proteins 973:980 Latent TGFβ-binding proteins 953:980 Latent TGFβ-binding proteins (LTBPs) 953:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 1 40 theme Growth 104:109 arg1 repeats 129:135 Epidermal Growth Factor-like (EGF) repeats 94:135 Epidermal Growth Factor-like (EGF) repeats 94:135 O-glycosylation of Epidermal Growth Factor-like (EGF) repeats plays crucial roles in protein folding, trafficking and function. 35411374 3 41 theme EGF 388:390 arg1 repeats 392:398 O-glycosylate Notch EGF repeats 368:398 O-glycosylate Notch EGF repeats 368:398 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 3 42 dep Domain 493:498 arg1 Transferase 538:548 O-Linked N-Acetylglucosamine Transferase 509:548 EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT) 489:555 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 3 42 dep Domain 493:498 arg1 EOGT 551:554 EOGT 551:554 EOGT 551:554 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 9 43 theme EGF 1306:1308 arg1 modifications 1310:1322 EGF modifications 1306:1322 EGF modifications 1306:1322 There is precedent for EGF modifications to affect protein-protein interactions, as has been demonstrated by research of POGLUT1 and POFUT1 modifications on Notch. 35411374 10 44 theme novel 1616:1620 arg1 enzymes 1622:1628 these novel enzymes 1610:1628 these novel enzymes 1610:1628 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 7 45 theme EGF 1058:1060 arg1 repeats 1062:1068 the 47 EGF repeats 1051:1068 the 47 EGF repeats in FBN1 and FBN2 1051:1085 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 6 46 theme consensus 835:843 arg1 sequence 845:852 a putative consensus sequence 824:852 a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs) 824:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 2 47 theme extracellular 213:225 arg1 domain 227:232 The Notch extracellular domain 203:232 The Notch extracellular domain 203:232 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 2 47 theme extracellular 213:225 arg1 model 253:257 a model 251:257 a model to study these mechanisms due to its many O-glycosylated EGF repeats 251:326 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 10 48 dep identification 1467:1480 arg1 the 1463:1465 the 1463:1465 the 1463:1465 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 3 49 theme O-glycosylate 368:380 arg1 repeats 392:398 O-glycosylate Notch EGF repeats 368:398 O-glycosylate Notch EGF repeats 368:398 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 7 50 from half 1092:1095 arg1 FBN2 1082:1085 FBN2 1082:1085 FBN2 1082:1085 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 50 from half 1092:1095 arg1 FBN1 1073:1076 FBN1 1073:1076 FBN1 1073:1076 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 50 from half 1092:1095 arg1 LTBP1 1122:1126 LTBP1 1122:1126 LTBP1 1122:1126 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 2 51 gly O-glycosylated 301:314 arg1 repeats 320:326 its many O-glycosylated EGF repeats 292:326 its many O-glycosylated EGF repeats 292:326 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 6 52 theme putative 826:833 arg1 sequence 845:852 a putative consensus sequence 824:852 a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs) 824:988 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 2 53 theme Notch 207:211 arg1 domain 227:232 The Notch extracellular domain 203:232 The Notch extracellular domain 203:232 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 2 53 theme Notch 207:211 arg1 model 253:257 a model 251:257 a model to study these mechanisms due to its many O-glycosylated EGF repeats 251:326 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 1 54 theme Factor-like 111:121 arg1 repeats 129:135 Epidermal Growth Factor-like (EGF) repeats 94:135 Epidermal Growth Factor-like (EGF) repeats 94:135 O-glycosylation of Epidermal Growth Factor-like (EGF) repeats plays crucial roles in protein folding, trafficking and function. 35411374 3 55 theme Notch 382:386 arg1 repeats 392:398 O-glycosylate Notch EGF repeats 368:398 O-glycosylate Notch EGF repeats 368:398 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 3 56 theme Protein 444:450 arg1 O-Fucosyltransferase 452:471 Protein O-Fucosyltransferase 1 444:473 Protein O-Fucosyltransferase 1 (POFUT1) 444:482 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 3 56 theme Protein 444:450 arg1 POFUT1 476:481 POFUT1 476:481 POFUT1 476:481 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 9 57 from research 1392:1399 arg1 Notch 1440:1444 Notch 1440:1444 Notch 1440:1444 There is precedent for EGF modifications to affect protein-protein interactions, as has been demonstrated by research of POGLUT1 and POFUT1 modifications on Notch. 35411374 7 58 theme Glycoproteomic 991:1004 arg1 analysis 1006:1013 Glycoproteomic analysis 991:1013 Glycoproteomic analysis 991:1013 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 2 59 theme O-glycosylated 301:314 arg1 repeats 320:326 its many O-glycosylated EGF repeats 292:326 its many O-glycosylated EGF repeats 292:326 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 10 60 theme enzymes 1622:1628 arg1 significance 1594:1605 the biological significance 1579:1605 the biological significance of these novel enzymes 1579:1628 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 1 61 theme EGF 124:126 arg1 repeats 129:135 Epidermal Growth Factor-like (EGF) repeats 94:135 Epidermal Growth Factor-like (EGF) repeats 94:135 O-glycosylation of Epidermal Growth Factor-like (EGF) repeats plays crucial roles in protein folding, trafficking and function. 35411374 3 62 theme N-Acetylglucosamine 518:536 arg1 Transferase 538:548 O-Linked N-Acetylglucosamine Transferase 509:548 EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT) 489:555 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 3 62 theme N-Acetylglucosamine 518:536 arg1 EOGT 551:554 EOGT 551:554 EOGT 551:554 Three enzymes were previously known to O-glycosylate Notch EGF repeats: Protein O-Glucosyltransferase 1 (POGLUT1), Protein O-Fucosyltransferase 1 (POFUT1), and EGF Domain Specific O-Linked N-Acetylglucosamine Transferase (EOGT). 35411374 5 63 theme novel 661:665 arg1 POGLUT3 630:636 POGLUT3 630:636 POGLUT3 630:636 Recently, POGLUT2 and POGLUT3 were identified as two novel O-glucosyltransferases that modify a few Notch EGF repeats at sites distinct from those modified by POGLUT1. 35411374 5 63 theme novel 661:665 arg1 POGLUT2 618:624 POGLUT2 618:624 POGLUT2 618:624 Recently, POGLUT2 and POGLUT3 were identified as two novel O-glucosyltransferases that modify a few Notch EGF repeats at sites distinct from those modified by POGLUT1. 35411374 5 63 theme novel 661:665 arg1 O-glucosyltransferases 667:688 two novel O-glucosyltransferases 657:688 two novel O-glucosyltransferases that modify a few Notch EGF repeats at sites distinct from those modified by POGLUT1 657:773 Recently, POGLUT2 and POGLUT3 were identified as two novel O-glucosyltransferases that modify a few Notch EGF repeats at sites distinct from those modified by POGLUT1. 35411374 6 64 theme sites 809:813 arg1 Comparison 776:785 Comparison 776:785 Comparison of these modification sites 776:813 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 8 65 theme FBN1 1267:1270 arg1 secretion 1272:1280 FBN1 secretion 1267:1280 FBN1 secretion 1267:1280 Cellular assays showed that loss of modifications by POGLUT2 and/or POGLUT3 significantly reduces FBN1 secretion. 35411374 2 66 theme many 296:299 arg1 repeats 320:326 its many O-glycosylated EGF repeats 292:326 its many O-glycosylated EGF repeats 292:326 The Notch extracellular domain has been used as a model to study these mechanisms due to its many O-glycosylated EGF repeats. 35411374 10 67 theme ongoing 1534:1540 arg1 research 1542:1549 the ongoing research 1530:1549 the ongoing research that continues to elucidate the biological significance of these novel enzymes 1530:1628 Here we discuss the identification and characterization of POGLUT2 and POGLUT3 and the ongoing research that continues to elucidate the biological significance of these novel enzymes. 35411374 6 68 theme modification 796:807 arg1 sites 809:813 these modification sites 790:813 these modification sites 790:813 Comparison of these modification sites revealed a putative consensus sequence which predicted modification of many extracellular matrix proteins including fibrillins (FBNs) and Latent TGFβ-binding proteins (LTBPs). 35411374 1 69 theme repeats 129:135 arg1 O-glycosylation 75:89 O-glycosylation 75:89 O-glycosylation of Epidermal Growth Factor-like (EGF) repeats 75:135 O-glycosylation of Epidermal Growth Factor-like (EGF) repeats plays crucial roles in protein folding, trafficking and function. 35411374 9 70 theme POFUT1 1416:1421 arg1 modifications 1423:1435 POGLUT1 and POFUT1 modifications 1404:1435 POGLUT1 and POFUT1 modifications 1404:1435 There is precedent for EGF modifications to affect protein-protein interactions, as has been demonstrated by research of POGLUT1 and POFUT1 modifications on Notch. 35411374 4 71 theme Notch 592:596 arg1 activity 598:605 Notch activity 592:605 Notch activity 592:605 All of these modifications affect Notch activity. 35411374 0 72 theme POGLUT2 54:60 arg1 function 16:23 function 16:23 function 16:23 Identification, function, and biological relevance of POGLUT2 and POGLUT3. 35411374 0 72 theme POGLUT2 54:60 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification, function, and biological relevance of POGLUT2 and POGLUT3. 35411374 0 72 theme POGLUT2 54:60 arg1 relevance 41:49 biological relevance 30:49 biological relevance 30:49 Identification, function, and biological relevance of POGLUT2 and POGLUT3. 35411374 7 73 mod modified 1133:1140 arg1 half 1092:1095 half 1092:1095 half of the 18 EGF repeats in LTBP1 1092:1126 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 73 mod modified 1133:1140 arg3 POGLUT2 1145:1151 POGLUT2 1145:1151 POGLUT2 1145:1151 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 73 mod modified 1133:1140 arg3 POGLUT3 1160:1166 POGLUT3 1160:1166 POGLUT3 1160:1166 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 7 73 mod modified 1133:1140 arg1 half 1043:1046 approximately half 1029:1046 approximately half of the 47 EGF repeats in FBN1 and FBN2 1029:1085 Glycoproteomic analysis revealed that approximately half of the 47 EGF repeats in FBN1 and FBN2, and half of the 18 EGF repeats in LTBP1, are modified by POGLUT2 and/or POGLUT3. 35411374 5 74 theme Notch 708:712 arg1 repeats 718:724 a few Notch EGF repeats 702:724 a few Notch EGF repeats 702:724 Recently, POGLUT2 and POGLUT3 were identified as two novel O-glucosyltransferases that modify a few Notch EGF repeats at sites distinct from those modified by POGLUT1. 35254053 6 0 theme stoichiometric 1116:1129 arg1 differences 1131:1141 The stoichiometric differences 1112:1141 The stoichiometric differences of 625 O-GlcNAcylation sites 1112:1170 The stoichiometric differences of 625 O-GlcNAcylation sites are quantified. 35254053 1 1 mod modification 258:269 arg1 importance 287:296 the emerging importance 274:296 the emerging importance in metazoans 274:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 1 1 mod modification 258:269 arg3 protein 231:237 a ubiquitous protein post-translational modification 218:269 a ubiquitous protein post-translational modification of the emerging importance in metazoans 218:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 7 2 theme quantified 1197:1206 arg1 sites 1208:1212 these quantified sites 1191:1212 these quantified sites 1191:1212 Of these quantified sites, many occur on important regulators involved in tumor progression and metastasis. 35254053 5 3 theme colorectal 979:988 arg1 lines 1008:1012 colorectal cancer (CRC) cell lines 979:1012 colorectal cancer (CRC) cell lines 979:1012 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 5 4 theme cancer 990:995 arg1 lines 1008:1012 colorectal cancer (CRC) cell lines 979:1012 colorectal cancer (CRC) cell lines 979:1012 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 5 5 theme lines 1008:1012 arg1 pair 971:974 a pair 969:974 a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively 969:1109 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 0 6 theme O-GlcNAcylation 110:124 arg1 Profiling 89:97 Site-Specific and Quantitative Profiling 58:97 Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis 58:156 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 4 7 theme sites 878:882 arg1 quantification 838:851 quantification 838:851 quantification of ∼1000 O-GlcNAcylation sites with isoPTOP 838:895 In HeLa cells, ∼1500 O-GlcNAcylation sites were identified with the optimized procedures, which led to quantification of ∼1000 O-GlcNAcylation sites with isoPTOP. 35254053 4 8 theme O-GlcNAcylation 756:770 arg1 sites 772:776 ∼1500 O-GlcNAcylation sites 750:776 ∼1500 O-GlcNAcylation sites 750:776 In HeLa cells, ∼1500 O-GlcNAcylation sites were identified with the optimized procedures, which led to quantification of ∼1000 O-GlcNAcylation sites with isoPTOP. 35254053 5 9 theme SW620 1025:1029 arg1 cells 1031:1035 SW620 cells 1025:1035 SW620 cells 1025:1035 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 5 10 theme primary 1054:1060 arg1 carcinoma 1062:1070 primary carcinoma 1054:1070 primary carcinoma 1054:1070 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 0 11 theme Protein 102:108 arg1 O-GlcNAcylation 110:124 Protein O-GlcNAcylation 102:124 Protein O-GlcNAcylation 102:124 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 5 12 theme cells 1031:1035 arg1 pair 971:974 a pair 969:974 a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively 969:1109 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 2 13 theme proteins 347:354 arg1 thousands 319:327 the thousands 315:327 the thousands of O-GlcNAcylated proteins identified 315:365 Of the thousands of O-GlcNAcylated proteins identified, many carry multiple modification sites with varied stoichiometry. 35254053 2 14 theme modification 388:399 arg1 sites 401:405 multiple modification sites 379:405 multiple modification sites 379:405 Of the thousands of O-GlcNAcylated proteins identified, many carry multiple modification sites with varied stoichiometry. 35254053 0 15 theme Colorectal 129:138 arg1 Metastasis 147:156 Colorectal Cancer Metastasis 129:156 Colorectal Cancer Metastasis 129:156 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 6 16 theme sites 1166:1170 arg1 differences 1131:1141 The stoichiometric differences 1112:1141 The stoichiometric differences of 625 O-GlcNAcylation sites 1112:1170 The stoichiometric differences of 625 O-GlcNAcylation sites are quantified. 35254053 2 17 theme O-GlcNAcylated 332:345 arg1 proteins 347:354 O-GlcNAcylated proteins 332:354 O-GlcNAcylated proteins identified 332:365 Of the thousands of O-GlcNAcylated proteins identified, many carry multiple modification sites with varied stoichiometry. 35254053 3 18 theme dynamic 488:494 arg1 nature 496:501 their dynamic nature 482:501 their dynamic nature 482:501 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 5 19 theme O-GlcNAcylation 941:955 arg1 dynamics 957:964 the O-GlcNAcylation dynamics 937:964 the O-GlcNAcylation dynamics 937:964 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 4 20 with sites 878:882 arg1 isoPTOP 889:895 isoPTOP 889:895 isoPTOP 889:895 In HeLa cells, ∼1500 O-GlcNAcylation sites were identified with the optimized procedures, which led to quantification of ∼1000 O-GlcNAcylation sites with isoPTOP. 35254053 4 21 theme ∼1000 856:860 arg1 sites 878:882 ∼1000 O-GlcNAcylation sites 856:882 ∼1000 O-GlcNAcylation sites with isoPTOP 856:895 In HeLa cells, ∼1500 O-GlcNAcylation sites were identified with the optimized procedures, which led to quantification of ∼1000 O-GlcNAcylation sites with isoPTOP. 35254053 3 22 with profiling 662:670 arg1 sensitivity 722:732 sensitivity 722:732 sensitivity 722:732 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 3 22 with profiling 662:670 arg1 specificity 706:716 excellent specificity 696:716 excellent specificity 696:716 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 0 23 theme Optimized 3:11 arg1 Strategy 45:52 An Optimized Isotopic Photocleavable Tagging Strategy 0:52 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 0:157 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 2 24 theme multiple 379:386 arg1 sites 401:405 multiple modification sites 379:405 multiple modification sites 379:405 Of the thousands of O-GlcNAcylated proteins identified, many carry multiple modification sites with varied stoichiometry. 35254053 1 25 theme ubiquitous 220:229 arg1 modification 258:269 a ubiquitous protein post-translational modification 218:269 a ubiquitous protein post-translational modification of the emerging importance in metazoans 218:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 1 25 theme ubiquitous 220:229 arg1 glycosylation 201:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 7 26 theme tumor 1262:1266 arg1 progression 1268:1278 tumor progression 1262:1278 tumor progression 1262:1278 Of these quantified sites, many occur on important regulators involved in tumor progression and metastasis. 35254053 4 27 theme optimized 803:811 arg1 procedures 813:822 the optimized procedures 799:822 the optimized procedures 799:822 In HeLa cells, ∼1500 O-GlcNAcylation sites were identified with the optimized procedures, which led to quantification of ∼1000 O-GlcNAcylation sites with isoPTOP. 35254053 9 28 theme pathophysiological 1477:1494 arg1 processes 1496:1504 various pathophysiological processes 1469:1504 various pathophysiological processes 1469:1504 IsoPTOP should be applicable for investigating O-GlcNAcylation dynamics in various pathophysiological processes. 35254053 3 29 theme quantitative 631:642 arg1 profiling 662:670 quantitative and site-specific profiling 631:670 quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity 631:732 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 1 30 theme protein 231:237 arg1 modification 258:269 a ubiquitous protein post-translational modification 218:269 a ubiquitous protein post-translational modification of the emerging importance in metazoans 218:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 1 30 theme protein 231:237 arg1 glycosylation 201:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 0 31 theme Photocleavable 22:35 arg1 Strategy 45:52 An Optimized Isotopic Photocleavable Tagging Strategy 0:52 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 0:157 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 6 32 theme O-GlcNAcylation 1150:1164 arg1 sites 1166:1170 625 O-GlcNAcylation sites 1146:1170 625 O-GlcNAcylation sites 1146:1170 The stoichiometric differences of 625 O-GlcNAcylation sites are quantified. 35254053 5 33 theme cell 1003:1006 arg1 lines 1008:1012 colorectal cancer (CRC) cell lines 979:1012 colorectal cancer (CRC) cell lines 979:1012 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 5 34 theme SW480 1015:1019 arg1 pair 971:974 a pair 969:974 a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively 969:1109 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 1 35 theme post-translational 239:256 arg1 modification 258:269 a ubiquitous protein post-translational modification 218:269 a ubiquitous protein post-translational modification of the emerging importance in metazoans 218:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 1 35 theme post-translational 239:256 arg1 glycosylation 201:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 0 36 theme Isotopic 13:20 arg1 Strategy 45:52 An Optimized Isotopic Photocleavable Tagging Strategy 0:52 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 0:157 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 9 37 theme O-GlcNAcylation 1441:1455 arg1 dynamics 1457:1464 O-GlcNAcylation dynamics 1441:1464 O-GlcNAcylation dynamics 1441:1464 IsoPTOP should be applicable for investigating O-GlcNAcylation dynamics in various pathophysiological processes. 35254053 0 38 theme Cancer 140:145 arg1 Metastasis 147:156 Colorectal Cancer Metastasis 129:156 Colorectal Cancer Metastasis 129:156 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 8 39 from role 1369:1372 arg1 CRC 1389:1391 CRC 1389:1391 CRC 1389:1391 Our results provide a valuable database for understanding the functional role of O-GlcNAc in CRC. 35254053 3 40 theme optimized 524:532 arg1 strategy 534:541 an optimized strategy 521:541 an optimized strategy 521:541 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 3 41 theme photocleavable 560:573 arg1 tagging 575:581 isotopic photocleavable tagging 551:581 isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP) 551:614 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 5 42 theme CRC 998:1000 arg1 lines 1008:1012 colorectal cancer (CRC) cell lines 979:1012 colorectal cancer (CRC) cell lines 979:1012 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 0 43 from Profiling 89:97 arg1 Metastasis 147:156 Colorectal Cancer Metastasis 129:156 Colorectal Cancer Metastasis 129:156 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 5 44 theme metastatic 1076:1085 arg1 cells 1087:1091 metastatic cells 1076:1091 metastatic cells 1076:1091 Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. 35254053 3 45 theme nature 496:501 arg1 scale 454:458 the scale 450:458 the scale of O-GlcNAc sites and their dynamic nature 450:501 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 0 46 theme Tagging 37:43 arg1 Strategy 45:52 An Optimized Isotopic Photocleavable Tagging Strategy 0:52 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 0:157 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 7 47 theme important 1229:1237 arg1 regulators 1239:1248 important regulators 1229:1248 important regulators involved in tumor progression and metastasis 1229:1293 Of these quantified sites, many occur on important regulators involved in tumor progression and metastasis. 35254053 0 48 theme Site-Specific 58:70 arg1 Profiling 89:97 Site-Specific and Quantitative Profiling 58:97 Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis 58:156 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 9 49 theme various 1469:1475 arg1 processes 1496:1504 various pathophysiological processes 1469:1504 various pathophysiological processes 1469:1504 IsoPTOP should be applicable for investigating O-GlcNAcylation dynamics in various pathophysiological processes. 35254053 2 50 theme varied 412:417 arg1 stoichiometry 419:431 varied stoichiometry 412:431 varied stoichiometry 412:431 Of the thousands of O-GlcNAcylated proteins identified, many carry multiple modification sites with varied stoichiometry. 35254053 3 51 theme sites 472:476 arg1 scale 454:458 the scale 450:458 the scale of O-GlcNAc sites and their dynamic nature 450:501 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 2 52 contain carry 373:377 arg1 many 368:371 many 368:371 many 368:371 Of the thousands of O-GlcNAcylated proteins identified, many carry multiple modification sites with varied stoichiometry. 35254053 2 52 contain carry 373:377 arg2 sites 401:405 multiple modification sites 379:405 multiple modification sites 379:405 Of the thousands of O-GlcNAcylated proteins identified, many carry multiple modification sites with varied stoichiometry. 35254053 1 53 from metazoans 301:309 arg1 modification 258:269 a ubiquitous protein post-translational modification 218:269 a ubiquitous protein post-translational modification of the emerging importance in metazoans 218:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 1 53 from metazoans 301:309 arg1 glycosylation 201:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 3 54 theme site-specific 648:660 arg1 profiling 662:670 quantitative and site-specific profiling 631:670 quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity 631:732 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 3 55 theme isotopic 551:558 arg1 tagging 575:581 isotopic photocleavable tagging 551:581 isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP) 551:614 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 3 56 theme excellent 696:704 arg1 specificity 706:716 excellent specificity 696:716 excellent specificity 696:716 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 1 57 from modification 258:269 arg1 metazoans 301:309 metazoans 301:309 metazoans 301:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 1 58 theme emerging 278:285 arg1 importance 287:296 the emerging importance 274:296 the emerging importance in metazoans 274:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 1 59 from importance 287:296 arg1 metazoans 301:309 metazoans 301:309 metazoans 301:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 4 60 theme O-GlcNAcylation 862:876 arg1 sites 878:882 ∼1000 O-GlcNAcylation sites 856:882 ∼1000 O-GlcNAcylation sites with isoPTOP 856:895 In HeLa cells, ∼1500 O-GlcNAcylation sites were identified with the optimized procedures, which led to quantification of ∼1000 O-GlcNAcylation sites with isoPTOP. 35254053 1 61 theme O-linked-β-N-acetylglucosamine 159:188 arg1 modification 258:269 a ubiquitous protein post-translational modification 218:269 a ubiquitous protein post-translational modification of the emerging importance in metazoans 218:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 1 61 theme O-linked-β-N-acetylglucosamine 159:188 arg1 glycosylation 201:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 1 62 theme importance 287:296 arg1 modification 258:269 a ubiquitous protein post-translational modification 218:269 a ubiquitous protein post-translational modification of the emerging importance in metazoans 218:309 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 1 62 theme importance 287:296 arg1 glycosylation 201:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation 159:213 O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. 35254053 0 63 theme Quantitative 76:87 arg1 Profiling 89:97 Site-Specific and Quantitative Profiling 58:97 Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis 58:156 An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. 35254053 3 64 theme O-GlcNAcylation 675:689 arg1 profiling 662:670 quantitative and site-specific profiling 631:670 quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity 631:732 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 8 65 theme functional 1358:1367 arg1 role 1369:1372 the functional role 1354:1372 the functional role of O-GlcNAc in CRC 1354:1391 Our results provide a valuable database for understanding the functional role of O-GlcNAc in CRC. 35254053 4 66 theme HeLa 738:741 arg1 cells 743:747 HeLa cells 738:747 HeLa cells 738:747 In HeLa cells, ∼1500 O-GlcNAcylation sites were identified with the optimized procedures, which led to quantification of ∼1000 O-GlcNAcylation sites with isoPTOP. 35254053 3 67 theme O-GlcNAc 463:470 arg1 sites 472:476 O-GlcNAc sites 463:476 O-GlcNAc sites 463:476 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 8 68 theme valuable 1318:1325 arg1 database 1327:1334 a valuable database 1316:1334 a valuable database for understanding the functional role of O-GlcNAc in CRC 1316:1391 Our results provide a valuable database for understanding the functional role of O-GlcNAc in CRC. 35254053 3 69 theme O-GlcNAc 587:594 arg1 isoPTOP 607:613 isoPTOP 607:613 isoPTOP 607:613 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 3 69 theme O-GlcNAc 587:594 arg1 profiling 596:604 O-GlcNAc profiling 587:604 O-GlcNAc profiling (isoPTOP) 587:614 To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. 35254053 8 70 theme O-GlcNAc 1377:1384 arg1 role 1369:1372 the functional role 1354:1372 the functional role of O-GlcNAc in CRC 1354:1391 Our results provide a valuable database for understanding the functional role of O-GlcNAc in CRC. 36916948 11 0 theme antibiotic 2272:2281 arg1 treatments 2283:2292 antibiotic treatments 2272:2292 antibiotic treatments 2272:2292 IMPORTANCE Mycobacteria include both saprophytes, such as the model system Mycobacterium smegmatis, and pathogens, such as Mycobacterium tuberculosis and Mycobacterium abscessus, that are poorly responsive to antibiotic treatments and pose a global public health problem. 36916948 6 1 theme potential 1196:1204 arg1 proteins 1226:1233 two potential additional adhesion proteins 1192:1233 two potential additional adhesion proteins 1192:1233 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 3 2 theme flexible 565:572 arg1 assemblies 585:594 large and flexible biological assemblies 555:594 large and flexible biological assemblies resistant to experimental methods 555:628 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 12 3 theme infection 2522:2530 arg1 mycobacteria 2464:2475 mycobacteria genetic manipulation, rapid diagnostics, and infection treatment 2464:2540 mycobacteria genetic manipulation, rapid diagnostics, and infection treatment 2464:2540 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 12 3 theme infection 2522:2530 arg1 treatment 2532:2540 infection treatment 2522:2540 infection treatment 2522:2540 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 2 4 theme host-binding 297:308 arg1 machineries 310:320 host-binding machineries 297:320 host-binding machineries 297:320 Here, we have explored the architecture of host-binding machineries from seven representative mycobacteriophages of the Siphoviridae family infecting Mycobacterium smegmatis, Mycobacterium abscessus, and Mycobacterium tuberculosis, using AlphaFold2 (AF2). 36916948 9 5 theme mycolic 1809:1815 arg1 acids 1817:1821 mycolic acids 1809:1821 mycolic acids 1809:1821 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 10 6 theme recombinant 1887:1897 arg1 proteins 1899:1906 recombinant proteins 1887:1906 recombinant proteins 1887:1906 This work provides a rational framework to efficiently produce recombinant proteins or protein domains and test their host-binding function and, hence, to shed light on molecular mechanisms used by mycobacteriophages to infect their host. 36916948 15 7 theme challenging 3066:3076 arg1 assemblies 3078:3087 such challenging assemblies 3061:3087 such challenging assemblies 3061:3087 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 2 8 theme representative 333:346 arg1 mycobacteriophages 348:365 seven representative mycobacteriophages 327:365 seven representative mycobacteriophages of the Siphoviridae family infecting Mycobacterium smegmatis, Mycobacterium abscessus, and Mycobacterium tuberculosis 327:483 Here, we have explored the architecture of host-binding machineries from seven representative mycobacteriophages of the Siphoviridae family infecting Mycobacterium smegmatis, Mycobacterium abscessus, and Mycobacterium tuberculosis, using AlphaFold2 (AF2). 36916948 1 9 theme knowledge 197:205 arg1 gap 207:209 a knowledge gap 195:209 a knowledge gap on their structure-function relationships 195:251 Although more than 12,000 bacteriophages infecting mycobacteria (mycobacteriophages) have been isolated so far, there is a knowledge gap on their structure-function relationships. 36916948 6 10 theme distal 1097:1102 arg1 Dit 1092:1094 the classical Dit 1078:1094 the classical Dit (distal tail) 1078:1108 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 6 10 theme distal 1097:1102 arg1 tail 1104:1107 distal tail 1097:1107 distal tail 1097:1107 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 9 11 from acids 1817:1821 arg1 rich 1781:1784 rich 1781:1784 rich 1781:1784 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 9 11 from acids 1817:1821 arg1 envelope 1762:1769 the peculiar mycobacterial cell envelope 1730:1769 the peculiar mycobacterial cell envelope 1730:1769 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 12 12 theme genetic 2477:2483 arg1 manipulation 2485:2496 genetic manipulation 2477:2496 genetic manipulation 2477:2496 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 12 12 theme genetic 2477:2483 arg1 mycobacteria 2464:2475 mycobacteria genetic manipulation, rapid diagnostics, and infection treatment 2464:2540 mycobacteria genetic manipulation, rapid diagnostics, and infection treatment 2464:2540 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 1 13 theme structure-function 220:237 arg1 relationships 239:251 their structure-function relationships 214:251 their structure-function relationships 214:251 Although more than 12,000 bacteriophages infecting mycobacteria (mycobacteriophages) have been isolated so far, there is a knowledge gap on their structure-function relationships. 36916948 14 14 theme bacteriophage-host 2800:2817 arg1 interactions 2819:2830 bacteriophage-host interactions 2800:2830 bacteriophage-host interactions 2800:2830 Therefore, exploring the structural diversity of mycobacteriophages' host-binding machineries is important not only to better understand viral diversity and bacteriophage-host interactions, but also to rationally develop biotechnological tools. 36916948 4 15 theme machineries 795:805 arg1 modularity 732:741 modularity 732:741 modularity 732:741 Our results highlight the modularity and structural diversity of siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection. 36916948 4 15 theme machineries 795:805 arg1 diversity 758:766 structural diversity 747:766 structural diversity 747:766 Our results highlight the modularity and structural diversity of siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection. 36916948 10 16 theme host-binding 1942:1953 arg1 function 1955:1962 their host-binding function 1936:1962 their host-binding function 1936:1962 This work provides a rational framework to efficiently produce recombinant proteins or protein domains and test their host-binding function and, hence, to shed light on molecular mechanisms used by mycobacteriophages to infect their host. 36916948 1 17 from gap 207:209 arg1 relationships 239:251 their structure-function relationships 214:251 their structure-function relationships 214:251 Although more than 12,000 bacteriophages infecting mycobacteria (mycobacteriophages) have been isolated so far, there is a knowledge gap on their structure-function relationships. 36916948 9 18 theme unique 1619:1624 arg1 composition 1626:1636 the unique composition 1615:1636 the unique composition of mycobacteriophages' host-binding machineries 1615:1684 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 12 19 theme valuable 2445:2452 arg1 tools 2454:2458 valuable tools 2445:2458 valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment 2445:2540 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 15 20 theme powerful 2897:2904 arg1 AlphaFold2 2944:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 10 21 theme protein 1911:1917 arg1 domains 1919:1925 protein domains 1911:1925 protein domains 1911:1925 This work provides a rational framework to efficiently produce recombinant proteins or protein domains and test their host-binding function and, hence, to shed light on molecular mechanisms used by mycobacteriophages to infect their host. 36916948 2 22 theme machineries 310:320 arg1 architecture 281:292 the architecture 277:292 the architecture of host-binding machineries 277:320 Here, we have explored the architecture of host-binding machineries from seven representative mycobacteriophages of the Siphoviridae family infecting Mycobacterium smegmatis, Mycobacterium abscessus, and Mycobacterium tuberculosis, using AlphaFold2 (AF2). 36916948 8 23 from nature 1581:1586 arg1 common 1571:1576 common 1571:1576 common 1571:1576 These polyglycine-rich domains, which have been observed in only five native proteins, may be a hallmark of mycobacteriophages' host-binding machineries, and they may be more common in nature than expected. 36916948 11 24 theme model 2125:2129 arg1 system 2131:2136 the model system 2121:2136 the model system Mycobacterium smegmatis 2121:2160 IMPORTANCE Mycobacteria include both saprophytes, such as the model system Mycobacterium smegmatis, and pathogens, such as Mycobacterium tuberculosis and Mycobacterium abscessus, that are poorly responsive to antibiotic treatments and pose a global public health problem. 36916948 6 25 theme tail-associated 1116:1130 arg1 Tal 1111:1113 Tal 1111:1113 Tal (tail-associated lysin) 1111:1137 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 6 25 theme tail-associated 1116:1130 arg1 lysin 1132:1136 tail-associated lysin 1116:1136 tail-associated lysin 1116:1136 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 4 26 theme siphophage 771:780 arg1 machineries 795:805 siphophage host-binding machineries 771:805 siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection 771:876 Our results highlight the modularity and structural diversity of siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection. 36916948 8 27 from common 1571:1576 arg1 nature 1581:1586 nature 1581:1586 nature 1581:1586 These polyglycine-rich domains, which have been observed in only five native proteins, may be a hallmark of mycobacteriophages' host-binding machineries, and they may be more common in nature than expected. 36916948 5 28 theme Gram-positive 1021:1033 arg1 actinobacteria 1035:1048 other Gram-positive actinobacteria 1015:1048 other Gram-positive actinobacteria 1015:1048 Interestingly, the studied mycobacteriophages' host-binding machineries present unique features compared with those of phages infecting other Gram-positive actinobacteria. 36916948 6 29 contain contain 1184:1190 arg1 them 1179:1182 them 1179:1182 them 1179:1182 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 6 29 contain contain 1184:1190 arg2 proteins 1226:1233 two potential additional adhesion proteins 1192:1233 two potential additional adhesion proteins 1192:1233 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 6 29 contain contain 1184:1190 arg1 five 1171:1174 five 1171:1174 five 1171:1174 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 10 30 dep produce 1879:1885 arg1 shed 1979:1982 shed 1979:1982 to shed light on molecular mechanisms used by mycobacteriophages to infect their host 1976:2060 This work provides a rational framework to efficiently produce recombinant proteins or protein domains and test their host-binding function and, hence, to shed light on molecular mechanisms used by mycobacteriophages to infect their host. 36916948 7 31 theme multiple 1294:1301 arg1 helices 1315:1321 multiple polyglycine helices 1294:1321 multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains 1294:1393 Moreover, we have identified brush-like domains formed of multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains. 36916948 6 32 theme them 1179:1182 arg1 them 1179:1182 them 1179:1182 them 1179:1182 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 6 32 theme them 1179:1182 arg1 five 1171:1174 five 1171:1174 five 1171:1174 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 3 33 theme assemblies 585:594 arg1 analyses 543:550 confident structural analyses 522:550 confident structural analyses of large and flexible biological assemblies resistant to experimental methods 522:628 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 5 34 theme mycobacteriophages 906:923 arg1 machineries 939:949 the studied mycobacteriophages' host-binding machineries 894:949 the studied mycobacteriophages' host-binding machineries 894:949 Interestingly, the studied mycobacteriophages' host-binding machineries present unique features compared with those of phages infecting other Gram-positive actinobacteria. 36916948 11 35 theme public 2312:2317 arg1 problem 2326:2332 a global public health problem 2303:2332 a global public health problem 2303:2332 IMPORTANCE Mycobacteria include both saprophytes, such as the model system Mycobacterium smegmatis, and pathogens, such as Mycobacterium tuberculosis and Mycobacterium abscessus, that are poorly responsive to antibiotic treatments and pose a global public health problem. 36916948 12 36 theme large 2384:2388 arg1 scale 2390:2394 a very large scale 2377:2394 a very large scale over the last decade 2377:2415 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 5 37 theme host-binding 926:937 arg1 machineries 939:949 the studied mycobacteriophages' host-binding machineries 894:949 the studied mycobacteriophages' host-binding machineries 894:949 Interestingly, the studied mycobacteriophages' host-binding machineries present unique features compared with those of phages infecting other Gram-positive actinobacteria. 36916948 10 38 theme molecular 1993:2001 arg1 mechanisms 2003:2012 molecular mechanisms 1993:2012 molecular mechanisms used by mycobacteriophages to infect their host 1993:2060 This work provides a rational framework to efficiently produce recombinant proteins or protein domains and test their host-binding function and, hence, to shed light on molecular mechanisms used by mycobacteriophages to infect their host. 36916948 12 39 theme last 2405:2408 arg1 decade 2410:2415 the last decade 2401:2415 the last decade 2401:2415 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 11 40 theme IMPORTANCE 2063:2072 arg1 Mycobacteria 2074:2085 IMPORTANCE Mycobacteria 2063:2085 IMPORTANCE Mycobacteria 2063:2085 IMPORTANCE Mycobacteria include both saprophytes, such as the model system Mycobacterium smegmatis, and pathogens, such as Mycobacterium tuberculosis and Mycobacterium abscessus, that are poorly responsive to antibiotic treatments and pose a global public health problem. 36916948 0 41 theme Mycobacteriophages 38:55 arg1 Machineries 23:33 Host-Binding Machineries 10:33 Host-Binding Machineries of Mycobacteriophages with AlphaFold2 10:71 Exploring Host-Binding Machineries of Mycobacteriophages with AlphaFold2. 36916948 7 42 theme brush-like 1265:1274 arg1 domains 1276:1282 brush-like domains 1265:1282 brush-like domains formed of multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains 1265:1393 Moreover, we have identified brush-like domains formed of multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains. 36916948 9 43 theme peculiar 1734:1741 arg1 rich 1781:1784 rich 1781:1784 rich 1781:1784 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 9 43 theme peculiar 1734:1741 arg1 envelope 1762:1769 the peculiar mycobacterial cell envelope 1730:1769 the peculiar mycobacterial cell envelope 1730:1769 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 7 44 theme potential 1360:1368 arg1 residues 1348:1355 hydrophobic residues 1336:1355 hydrophobic residues 1336:1355 Moreover, we have identified brush-like domains formed of multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains. 36916948 7 44 theme potential 1360:1368 arg1 domains 1387:1393 potential receptor-binding domains 1360:1393 potential receptor-binding domains 1360:1393 Moreover, we have identified brush-like domains formed of multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains. 36916948 0 45 with Machineries 23:33 arg1 AlphaFold2 62:71 AlphaFold2 62:71 AlphaFold2 62:71 Exploring Host-Binding Machineries of Mycobacteriophages with AlphaFold2. 36916948 10 46 theme rational 1845:1852 arg1 framework 1854:1862 a rational framework 1843:1862 a rational framework to efficiently produce recombinant proteins or protein domains and test their host-binding function and, hence, to shed light on molecular mechanisms used by mycobacteriophages to infect their host 1843:2060 This work provides a rational framework to efficiently produce recombinant proteins or protein domains and test their host-binding function and, hence, to shed light on molecular mechanisms used by mycobacteriophages to infect their host. 36916948 15 47 theme structure 2914:2922 arg1 AlphaFold2 2944:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 9 48 theme cell 1757:1760 arg1 rich 1781:1784 rich 1781:1784 rich 1781:1784 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 9 48 theme cell 1757:1760 arg1 envelope 1762:1769 the peculiar mycobacterial cell envelope 1730:1769 the peculiar mycobacterial cell envelope 1730:1769 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 3 49 theme phage 676:680 arg1 structure 682:690 phage structure 676:690 phage structure 676:690 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 3 50 theme structural 532:541 arg1 analyses 543:550 confident structural analyses 522:550 confident structural analyses of large and flexible biological assemblies resistant to experimental methods 522:628 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 12 51 dep mycobacteria 2464:2475 arg1 manipulation 2485:2496 genetic manipulation 2477:2496 genetic manipulation 2477:2496 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 12 51 dep mycobacteria 2464:2475 arg1 diagnostics 2505:2515 rapid diagnostics 2499:2515 rapid diagnostics 2499:2515 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 12 51 dep mycobacteria 2464:2475 arg1 mycobacteria 2464:2475 mycobacteria genetic manipulation, rapid diagnostics, and infection treatment 2464:2540 mycobacteria genetic manipulation, rapid diagnostics, and infection treatment 2464:2540 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 12 51 dep mycobacteria 2464:2475 arg1 treatment 2532:2540 infection treatment 2522:2540 infection treatment 2522:2540 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 14 52 theme structural 2668:2677 arg1 diversity 2679:2687 the structural diversity 2664:2687 the structural diversity of mycobacteriophages' host-binding machineries 2664:2735 Therefore, exploring the structural diversity of mycobacteriophages' host-binding machineries is important not only to better understand viral diversity and bacteriophage-host interactions, but also to rationally develop biotechnological tools. 36916948 4 53 dep modularity 732:741 arg1 the 728:730 the 728:730 the 728:730 Our results highlight the modularity and structural diversity of siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection. 36916948 3 54 theme biological 574:583 arg1 assemblies 585:594 large and flexible biological assemblies 555:594 large and flexible biological assemblies resistant to experimental methods 555:628 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 6 55 theme additional 1206:1215 arg1 proteins 1226:1233 two potential additional adhesion proteins 1192:1233 two potential additional adhesion proteins 1192:1233 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 3 56 theme experimental 609:620 arg1 methods 622:628 experimental methods 609:628 experimental methods 609:628 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 9 57 theme host-binding 1661:1672 arg1 machineries 1674:1684 mycobacteriophages' host-binding machineries 1641:1684 mycobacteriophages' host-binding machineries 1641:1684 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 15 58 from insights 3049:3056 arg1 assemblies 3078:3087 such challenging assemblies 3061:3087 such challenging assemblies 3061:3087 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 2 59 theme family 387:392 arg1 mycobacteriophages 348:365 seven representative mycobacteriophages 327:365 seven representative mycobacteriophages of the Siphoviridae family infecting Mycobacterium smegmatis, Mycobacterium abscessus, and Mycobacterium tuberculosis 327:483 Here, we have explored the architecture of host-binding machineries from seven representative mycobacteriophages of the Siphoviridae family infecting Mycobacterium smegmatis, Mycobacterium abscessus, and Mycobacterium tuberculosis, using AlphaFold2 (AF2). 36916948 3 60 theme resistant 596:604 arg1 assemblies 585:594 large and flexible biological assemblies 555:594 large and flexible biological assemblies resistant to experimental methods 555:628 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 14 61 theme biotechnological 2864:2879 arg1 tools 2881:2885 biotechnological tools 2864:2885 biotechnological tools 2864:2885 Therefore, exploring the structural diversity of mycobacteriophages' host-binding machineries is important not only to better understand viral diversity and bacteriophage-host interactions, but also to rationally develop biotechnological tools. 36916948 11 62 theme global 2305:2310 arg1 problem 2326:2332 a global public health problem 2303:2332 a global public health problem 2303:2332 IMPORTANCE Mycobacteria include both saprophytes, such as the model system Mycobacterium smegmatis, and pathogens, such as Mycobacterium tuberculosis and Mycobacterium abscessus, that are poorly responsive to antibiotic treatments and pose a global public health problem. 36916948 15 63 theme functional 3038:3047 arg1 insights 3049:3056 structural and functional insights 3023:3056 structural and functional insights on such challenging assemblies 3023:3087 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 3 64 theme new 647:649 arg1 avenues 651:657 new avenues 647:657 new avenues 647:657 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 15 65 theme such 3061:3064 arg1 assemblies 3078:3087 such challenging assemblies 3061:3087 such challenging assemblies 3061:3087 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 8 66 theme polyglycine-rich 1402:1417 arg1 domains 1419:1425 These polyglycine-rich domains 1396:1425 These polyglycine-rich domains 1396:1425 These polyglycine-rich domains, which have been observed in only five native proteins, may be a hallmark of mycobacteriophages' host-binding machineries, and they may be more common in nature than expected. 36916948 8 66 theme polyglycine-rich 1402:1417 arg1 hallmark 1492:1499 a hallmark 1490:1499 a hallmark of mycobacteriophages' host-binding machineries 1490:1547 These polyglycine-rich domains, which have been observed in only five native proteins, may be a hallmark of mycobacteriophages' host-binding machineries, and they may be more common in nature than expected. 36916948 2 67 theme Siphoviridae 374:385 arg1 family 387:392 the Siphoviridae family 370:392 the Siphoviridae family infecting Mycobacterium smegmatis, Mycobacterium abscessus, and Mycobacterium tuberculosis 370:483 Here, we have explored the architecture of host-binding machineries from seven representative mycobacteriophages of the Siphoviridae family infecting Mycobacterium smegmatis, Mycobacterium abscessus, and Mycobacterium tuberculosis, using AlphaFold2 (AF2). 36916948 15 68 theme structural 3023:3032 arg1 insights 3049:3056 structural and functional insights 3023:3056 structural and functional insights on such challenging assemblies 3023:3087 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 5 69 theme unique 959:964 arg1 features 966:973 unique features 959:973 unique features 959:973 Interestingly, the studied mycobacteriophages' host-binding machineries present unique features compared with those of phages infecting other Gram-positive actinobacteria. 36916948 6 70 theme classical 1082:1090 arg1 Dit 1092:1094 the classical Dit 1078:1094 the classical Dit (distal tail) 1078:1108 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 6 70 theme classical 1082:1090 arg1 tail 1104:1107 distal tail 1097:1107 distal tail 1097:1107 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 12 71 theme rapid 2499:2503 arg1 diagnostics 2505:2515 rapid diagnostics 2499:2515 rapid diagnostics 2499:2515 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 12 71 theme rapid 2499:2503 arg1 mycobacteria 2464:2475 mycobacteria genetic manipulation, rapid diagnostics, and infection treatment 2464:2540 mycobacteria genetic manipulation, rapid diagnostics, and infection treatment 2464:2540 Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment. 36916948 9 72 from rich 1781:1784 arg1 polysaccharides 1789:1803 polysaccharides 1789:1803 polysaccharides 1789:1803 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 9 72 from rich 1781:1784 arg1 acids 1817:1821 mycolic acids 1809:1821 mycolic acids 1809:1821 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 4 73 theme host-binding 782:793 arg1 machineries 795:805 siphophage host-binding machineries 771:805 siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection 771:876 Our results highlight the modularity and structural diversity of siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection. 36916948 11 74 theme system 2131:2136 arg1 smegmatis 2152:2160 the model system Mycobacterium smegmatis 2121:2160 the model system Mycobacterium smegmatis 2121:2160 IMPORTANCE Mycobacteria include both saprophytes, such as the model system Mycobacterium smegmatis, and pathogens, such as Mycobacterium tuberculosis and Mycobacterium abscessus, that are poorly responsive to antibiotic treatments and pose a global public health problem. 36916948 14 75 theme viral 2780:2784 arg1 diversity 2786:2794 viral diversity 2780:2794 viral diversity 2780:2794 Therefore, exploring the structural diversity of mycobacteriophages' host-binding machineries is important not only to better understand viral diversity and bacteriophage-host interactions, but also to rationally develop biotechnological tools. 36916948 4 76 theme structural 747:756 arg1 diversity 758:766 structural diversity 747:766 structural diversity 747:766 Our results highlight the modularity and structural diversity of siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection. 36916948 7 77 theme hydrophobic 1336:1346 arg1 residues 1348:1355 hydrophobic residues 1336:1355 hydrophobic residues 1336:1355 Moreover, we have identified brush-like domains formed of multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains. 36916948 7 77 theme hydrophobic 1336:1346 arg1 domains 1387:1393 potential receptor-binding domains 1360:1393 potential receptor-binding domains 1360:1393 Moreover, we have identified brush-like domains formed of multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains. 36916948 5 78 theme other 1015:1019 arg1 actinobacteria 1035:1048 other Gram-positive actinobacteria 1015:1048 other Gram-positive actinobacteria 1015:1048 Interestingly, the studied mycobacteriophages' host-binding machineries present unique features compared with those of phages infecting other Gram-positive actinobacteria. 36916948 8 79 theme native 1466:1471 arg1 proteins 1473:1480 only five native proteins 1456:1480 only five native proteins 1456:1480 These polyglycine-rich domains, which have been observed in only five native proteins, may be a hallmark of mycobacteriophages' host-binding machineries, and they may be more common in nature than expected. 36916948 10 80 dep framework 1854:1862 arg1 test 1931:1934 test 1931:1934 test their host-binding function 1931:1962 This work provides a rational framework to efficiently produce recombinant proteins or protein domains and test their host-binding function and, hence, to shed light on molecular mechanisms used by mycobacteriophages to infect their host. 36916948 10 80 dep framework 1854:1862 arg1 produce 1879:1885 produce 1879:1885 produce recombinant proteins or protein domains 1879:1925 This work provides a rational framework to efficiently produce recombinant proteins or protein domains and test their host-binding function and, hence, to shed light on molecular mechanisms used by mycobacteriophages to infect their host. 36916948 7 81 theme polyglycine 1303:1313 arg1 helices 1315:1321 multiple polyglycine helices 1294:1321 multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains 1294:1393 Moreover, we have identified brush-like domains formed of multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains. 36916948 15 82 theme software 2935:2942 arg1 AlphaFold2 2944:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 4 83 theme viral 862:866 arg1 infection 868:876 viral infection 862:876 viral infection 862:876 Our results highlight the modularity and structural diversity of siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection. 36916948 5 84 theme studied 898:904 arg1 machineries 939:949 the studied mycobacteriophages' host-binding machineries 894:949 the studied mycobacteriophages' host-binding machineries 894:949 Interestingly, the studied mycobacteriophages' host-binding machineries present unique features compared with those of phages infecting other Gram-positive actinobacteria. 36916948 13 85 theme molecular 2548:2556 arg1 mechanisms 2558:2567 molecular mechanisms 2548:2567 molecular mechanisms used by mycobacteriophages to infect their host 2548:2615 Yet, molecular mechanisms used by mycobacteriophages to infect their host remain poorly understood. 36916948 4 86 theme host-specific 822:834 arg1 receptors 836:844 host-specific receptors 822:844 host-specific receptors 822:844 Our results highlight the modularity and structural diversity of siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection. 36916948 11 87 theme health 2319:2324 arg1 problem 2326:2332 a global public health problem 2303:2332 a global public health problem 2303:2332 IMPORTANCE Mycobacteria include both saprophytes, such as the model system Mycobacterium smegmatis, and pathogens, such as Mycobacterium tuberculosis and Mycobacterium abscessus, that are poorly responsive to antibiotic treatments and pose a global public health problem. 36916948 4 88 theme infection 868:876 arg1 onset 853:857 the onset 849:857 the onset of viral infection 849:876 Our results highlight the modularity and structural diversity of siphophage host-binding machineries that recognize host-specific receptors at the onset of viral infection. 36916948 3 89 theme confident 522:530 arg1 analyses 543:550 confident structural analyses 522:550 confident structural analyses of large and flexible biological assemblies resistant to experimental methods 522:628 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 15 90 theme prediction 2924:2933 arg1 AlphaFold2 2944:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 8 91 located observed 1444:1451 arg2 domains 1419:1425 These polyglycine-rich domains 1396:1425 These polyglycine-rich domains 1396:1425 These polyglycine-rich domains, which have been observed in only five native proteins, may be a hallmark of mycobacteriophages' host-binding machineries, and they may be more common in nature than expected. 36916948 8 91 located observed 1444:1451 arg2 hallmark 1492:1499 a hallmark 1490:1499 a hallmark of mycobacteriophages' host-binding machineries 1490:1547 These polyglycine-rich domains, which have been observed in only five native proteins, may be a hallmark of mycobacteriophages' host-binding machineries, and they may be more common in nature than expected. 36916948 8 91 located observed 1444:1451 arg1 proteins 1473:1480 only five native proteins 1456:1480 only five native proteins 1456:1480 These polyglycine-rich domains, which have been observed in only five native proteins, may be a hallmark of mycobacteriophages' host-binding machineries, and they may be more common in nature than expected. 36916948 14 92 theme host-binding 2712:2723 arg1 machineries 2725:2735 mycobacteriophages' host-binding machineries 2692:2735 mycobacteriophages' host-binding machineries 2692:2735 Therefore, exploring the structural diversity of mycobacteriophages' host-binding machineries is important not only to better understand viral diversity and bacteriophage-host interactions, but also to rationally develop biotechnological tools. 36916948 6 93 theme receptor-binding 1144:1159 arg1 proteins 1161:1168 receptor-binding proteins 1144:1168 receptor-binding proteins 1144:1168 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 8 94 theme host-binding 1524:1535 arg1 machineries 1537:1547 mycobacteriophages' host-binding machineries 1504:1547 mycobacteriophages' host-binding machineries 1504:1547 These polyglycine-rich domains, which have been observed in only five native proteins, may be a hallmark of mycobacteriophages' host-binding machineries, and they may be more common in nature than expected. 36916948 15 95 theme protein 2906:2912 arg1 AlphaFold2 2944:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 9 96 from polysaccharides 1789:1803 arg1 rich 1781:1784 rich 1781:1784 rich 1781:1784 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 9 96 from polysaccharides 1789:1803 arg1 envelope 1762:1769 the peculiar mycobacterial cell envelope 1730:1769 the peculiar mycobacterial cell envelope 1730:1769 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 9 97 theme mycobacterial 1743:1755 arg1 rich 1781:1784 rich 1781:1784 rich 1781:1784 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 9 97 theme mycobacterial 1743:1755 arg1 envelope 1762:1769 the peculiar mycobacterial cell envelope 1730:1769 the peculiar mycobacterial cell envelope 1730:1769 Altogether, the unique composition of mycobacteriophages' host-binding machineries indicate they might have evolved to bind to the peculiar mycobacterial cell envelope, which is rich in polysaccharides and mycolic acids. 36916948 3 98 theme large 555:559 arg1 assemblies 585:594 large and flexible biological assemblies 555:594 large and flexible biological assemblies resistant to experimental methods 555:628 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 11 99 theme Mycobacterium 2138:2150 arg1 smegmatis 2152:2160 the model system Mycobacterium smegmatis 2121:2160 the model system Mycobacterium smegmatis 2121:2160 IMPORTANCE Mycobacteria include both saprophytes, such as the model system Mycobacterium smegmatis, and pathogens, such as Mycobacterium tuberculosis and Mycobacterium abscessus, that are poorly responsive to antibiotic treatments and pose a global public health problem. 36916948 3 100 dep enables 514:520 arg1 opening 639:645 opening 639:645 opening 639:645 AF2 enables confident structural analyses of large and flexible biological assemblies resistant to experimental methods, thereby opening new avenues to shed light on phage structure and function. 36916948 6 101 theme adhesion 1217:1224 arg1 proteins 1226:1233 two potential additional adhesion proteins 1192:1233 two potential additional adhesion proteins 1192:1233 Although they all assemble the classical Dit (distal tail), Tal (tail-associated lysin), and receptor-binding proteins, five of them contain two potential additional adhesion proteins. 36916948 15 102 with possible 3006:3013 arg1 AlphaFold2 2944:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 the powerful protein structure prediction software AlphaFold2 2893:2953 With the powerful protein structure prediction software AlphaFold2, which was publicly released a year ago, it is now possible to gain structural and functional insights on such challenging assemblies. 36916948 0 103 theme Host-Binding 10:21 arg1 Machineries 23:33 Host-Binding Machineries 10:33 Host-Binding Machineries of Mycobacteriophages with AlphaFold2 10:71 Exploring Host-Binding Machineries of Mycobacteriophages with AlphaFold2. 36916948 7 104 theme receptor-binding 1370:1385 arg1 residues 1348:1355 hydrophobic residues 1336:1355 hydrophobic residues 1336:1355 Moreover, we have identified brush-like domains formed of multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains. 36916948 7 104 theme receptor-binding 1370:1385 arg1 domains 1387:1393 potential receptor-binding domains 1360:1393 potential receptor-binding domains 1360:1393 Moreover, we have identified brush-like domains formed of multiple polyglycine helices which expose hydrophobic residues as potential receptor-binding domains. 36693567 7 0 theme chicory 1016:1022 arg1 Administration 985:998 RESULTS Administration 977:998 RESULTS Administration of kale and red chicory 977:1022 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 4 1 theme insoluble 562:570 arg1 fiber 580:584 celery insoluble dietary fiber 555:584 celery insoluble dietary fiber (CIDF) 555:591 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 1 theme insoluble 562:570 arg1 CIDF 587:590 CIDF 587:590 CIDF 587:590 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 11 2 theme g_Akkermansia 1596:1608 arg1 proliferation 1610:1622 g_Akkermansia proliferation 1596:1622 g_Akkermansia proliferation 1596:1622 Interestingly, celery flavonoid promoted g_Akkermansia proliferation both in vivo and in vitro, and which can be inhibited by CSDF. 36693567 4 3 theme mice 645:648 arg1 model 650:654 IBD mice model 641:654 IBD mice model 641:654 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 5 4 theme Dextran 768:774 arg1 DSS 797:799 3% Dextran sulfate sodium salt (DSS) 765:800 METHODS 3% Dextran sulfate sodium salt (DSS) 757:800 METHODS 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. 36693567 7 5 theme RESULTS 977:983 arg1 Administration 985:998 RESULTS Administration 977:998 RESULTS Administration of kale and red chicory 977:1022 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 5 6 theme sodium 784:789 arg1 DSS 797:799 3% Dextran sulfate sodium salt (DSS) 765:800 METHODS 3% Dextran sulfate sodium salt (DSS) 757:800 METHODS 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. 36693567 12 7 theme whole 1891:1895 arg1 food 1897:1900 celery whole food 1884:1900 celery whole food 1884:1900 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 6 8 theme biological 860:869 arg1 methods 871:877 Multiple molecular biological methods 841:877 Multiple molecular biological methods 841:877 Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. 36693567 10 9 theme intestinal 1456:1465 arg1 g_Escherichia-Shihella 1467:1488 intestinal g_Escherichia-Shihella 1456:1488 intestinal g_Escherichia-Shihella 1456:1488 Furthermore, CSDF and CF decreased intestinal g_Escherichia-Shihella and g_Clostridium_sensu_stricto_1 induced by DSS administration. 36693567 1 10 theme bowel 229:233 arg1 IBD 244:246 IBD 244:246 IBD 244:246 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 1 10 theme bowel 229:233 arg1 disease 235:241 inflammatory bowel disease 216:241 inflammatory bowel disease (IBD) 216:247 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 6 11 theme Multiple 841:848 arg1 methods 871:877 Multiple molecular biological methods 841:877 Multiple molecular biological methods 841:877 Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. 36693567 0 12 from colitis 105:111 arg1 mice 116:119 mice 116:119 mice 116:119 Celery soluble dietary fiber antagonize flavonoids ameliorative effect on dextran-sodium-sulfate-induced colitis in mice. 36693567 4 13 theme flavonoids 601:610 arg1 efficacy 492:499 the efficacy 488:499 the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model 488:654 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 10 14 theme DSS 1535:1537 arg1 administration 1539:1552 DSS administration 1535:1552 DSS administration 1535:1552 Furthermore, CSDF and CF decreased intestinal g_Escherichia-Shihella and g_Clostridium_sensu_stricto_1 induced by DSS administration. 36693567 3 15 from effect 367:372 arg1 mice 426:429 colitis mice 418:429 colitis mice using non-group feeding cages 418:459 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 12 16 theme decreased 1862:1870 arg1 efficacy 1872:1879 the decreased efficacy 1858:1879 the decreased efficacy of celery whole food on colitis 1858:1911 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 8 17 theme CSDF 1169:1172 arg1 Administration 1144:1157 Administration 1144:1157 Administration of either CSDF or CF 1144:1178 Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. 36693567 4 18 from efficacy 492:499 arg1 model 650:654 IBD mice model 641:654 IBD mice model 641:654 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 2 19 from interaction 277:287 arg1 health 333:338 gut health 329:338 gut health 329:338 However, it is unclear the interaction between dietary fiber and flavonoids in gut health. 36693567 8 20 theme CF 1177:1178 arg1 Administration 1144:1157 Administration 1144:1157 Administration of either CSDF or CF 1144:1178 Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. 36693567 4 21 from s 730:730 arg1 matrix 749:754 such complex matrix 736:754 such complex matrix 736:754 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 7 22 theme DAI 1060:1062 arg1 score 1064:1068 DAI score 1060:1068 DAI score 1060:1068 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 1 23 theme promising 171:179 arg1 flavonoids 156:165 flavonoids 156:165 flavonoids 156:165 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 1 23 theme promising 171:179 arg1 drugs 181:185 promising drugs 171:185 promising drugs reported in the treatment of inflammatory bowel disease (IBD) 171:247 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 1 23 theme promising 171:179 arg1 fiber 146:150 ***Introduction Dietary fiber 122:150 ***Introduction Dietary fiber 122:150 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 8 24 theme histological 1202:1213 arg1 damage 1215:1220 the histological damage 1198:1220 the histological damage 1198:1220 Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. 36693567 9 25 theme biochemical 1402:1412 arg1 signs 1414:1418 most physical and biochemical signs 1384:1418 most physical and biochemical signs 1384:1418 However, CSDF+CF showed weaker improvement than CF or SDF in most physical and biochemical signs. 36693567 7 26 from weight 1052:1057 arg1 mice 1099:1102 colonic mice 1091:1102 colonic mice 1091:1102 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 12 27 theme fiber 2122:2126 arg1 efficacy 2102:2109 the efficacy 2098:2109 the efficacy of dietary fiber or flavonoids 2098:2140 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 8 28 theme colonic 1233:1239 arg1 expression 1247:1256 colonic mucus expression 1233:1256 colonic mucus expression 1233:1256 Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. 36693567 7 29 theme colon 1075:1079 arg1 length 1081:1086 colon length 1075:1086 colon length 1075:1086 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 0 30 theme flavonoids 40:49 arg1 effect 64:69 flavonoids ameliorative effect 40:69 flavonoids ameliorative effect on dextran-sodium-sulfate-induced colitis in mice 40:119 Celery soluble dietary fiber antagonize flavonoids ameliorative effect on dextran-sodium-sulfate-induced colitis in mice. 36693567 3 31 theme kale 385:388 arg1 effect 367:372 The therapeutic effect 351:372 The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages 351:459 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 0 32 theme Celery 0:5 arg1 fiber 23:27 Celery soluble dietary fiber 0:27 Celery soluble dietary fiber 0:27 Celery soluble dietary fiber antagonize flavonoids ameliorative effect on dextran-sodium-sulfate-induced colitis in mice. 36693567 5 33 theme colitis 826:832 arg1 model 834:838 mice colitis model 821:838 mice colitis model 821:838 METHODS 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. 36693567 6 34 theme microbial 946:954 arg1 composition 956:966 the gut microbial composition 938:966 the gut microbial composition of mice 938:974 Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. 36693567 3 35 theme celery 377:382 arg1 effect 367:372 The therapeutic effect 351:372 The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages 351:459 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 4 36 theme dietary 533:539 arg1 fiber 541:545 celery soluble dietary fiber 518:545 celery soluble dietary fiber (CSDF) 518:552 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 36 theme dietary 533:539 arg1 CSDF 548:551 CSDF 548:551 CSDF 548:551 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 37 theme protective 680:689 arg1 effect 691:696 protective effect 680:696 protective effect 680:696 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 0 38 theme dietary 15:21 arg1 fiber 23:27 Celery soluble dietary fiber 0:27 Celery soluble dietary fiber 0:27 Celery soluble dietary fiber antagonize flavonoids ameliorative effect on dextran-sodium-sulfate-induced colitis in mice. 36693567 12 39 theme protective 1765:1774 arg1 effect 1776:1781 the protective effect 1761:1781 the protective effect of CF 1761:1787 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 1 40 theme Introduction 125:136 arg1 flavonoids 156:165 flavonoids 156:165 flavonoids 156:165 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 1 40 theme Introduction 125:136 arg1 drugs 181:185 promising drugs 171:185 promising drugs reported in the treatment of inflammatory bowel disease (IBD) 171:247 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 1 40 theme Introduction 125:136 arg1 fiber 146:150 ***Introduction Dietary fiber 122:150 ***Introduction Dietary fiber 122:150 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 3 41 theme chicory 399:405 arg1 powders 407:413 red chicory powders 395:413 red chicory powders 395:413 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 8 42 theme colonic 1271:1277 arg1 activities 1288:1297 colonic MPO/iNOS activities 1271:1297 colonic MPO/iNOS activities 1271:1297 Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. 36693567 3 43 theme non-group 437:445 arg1 cages 455:459 non-group feeding cages 437:459 non-group feeding cages 437:459 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 12 44 theme dietary 2046:2052 arg1 fiber 2054:2058 soluble dietary fiber 2038:2058 soluble dietary fiber 2038:2058 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 9 45 from improvement 1354:1364 arg1 signs 1414:1418 most physical and biochemical signs 1384:1418 most physical and biochemical signs 1384:1418 However, CSDF+CF showed weaker improvement than CF or SDF in most physical and biochemical signs. 36693567 6 46 theme colitis 926:932 arg1 severity 909:916 the severity 905:916 the severity of mice colitis 905:932 Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. 36693567 6 46 theme colitis 926:932 arg1 composition 956:966 the gut microbial composition 938:966 the gut microbial composition of mice 938:974 Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. 36693567 4 47 theme celery 510:515 arg1 efficacy 492:499 the efficacy 488:499 the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model 488:654 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 48 theme complex 741:747 arg1 matrix 749:754 such complex matrix 736:754 such complex matrix 736:754 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 0 49 theme ameliorative 51:62 arg1 effect 64:69 flavonoids ameliorative effect 40:69 flavonoids ameliorative effect on dextran-sodium-sulfate-induced colitis in mice 40:119 Celery soluble dietary fiber antagonize flavonoids ameliorative effect on dextran-sodium-sulfate-induced colitis in mice. 36693567 4 50 theme celery 518:523 arg1 fiber 541:545 celery soluble dietary fiber 518:545 celery soluble dietary fiber (CSDF) 518:552 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 50 theme celery 518:523 arg1 CSDF 548:551 CSDF 548:551 CSDF 548:551 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 5 51 dep METHODS 757:763 arg1 DSS 797:799 3% Dextran sulfate sodium salt (DSS) 765:800 METHODS 3% Dextran sulfate sodium salt (DSS) 757:800 METHODS 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. 36693567 12 52 theme first 1727:1731 arg1 time 1733:1736 the first time 1723:1736 the first time 1723:1736 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 9 53 theme physical 1389:1396 arg1 signs 1414:1418 most physical and biochemical signs 1384:1418 most physical and biochemical signs 1384:1418 However, CSDF+CF showed weaker improvement than CF or SDF in most physical and biochemical signs. 36693567 4 54 theme dietary 572:578 arg1 fiber 580:584 celery insoluble dietary fiber 555:584 celery insoluble dietary fiber (CIDF) 555:591 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 54 theme dietary 572:578 arg1 CIDF 587:590 CIDF 587:590 CIDF 587:590 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 7 55 theme weakest 1127:1133 arg1 effects 1135:1141 the weakest effects 1123:1141 the weakest effects 1123:1141 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 11 56 theme celery 1570:1575 arg1 flavonoid 1577:1585 celery flavonoid 1570:1585 celery flavonoid 1570:1585 Interestingly, celery flavonoid promoted g_Akkermansia proliferation both in vivo and in vitro, and which can be inhibited by CSDF. 36693567 7 57 theme red 1012:1014 arg1 chicory 1016:1022 red chicory 1012:1022 red chicory 1012:1022 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 7 58 theme kale 1003:1006 arg1 Administration 985:998 RESULTS Administration 977:998 RESULTS Administration of kale and red chicory 977:1022 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 2 59 theme dietary 297:303 arg1 fiber 305:309 dietary fiber 297:309 dietary fiber 297:309 However, it is unclear the interaction between dietary fiber and flavonoids in gut health. 36693567 12 60 theme food 1897:1900 arg1 efficacy 1872:1879 the decreased efficacy 1858:1879 the decreased efficacy of celery whole food on colitis 1858:1911 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 4 61 theme celery 555:560 arg1 fiber 580:584 celery insoluble dietary fiber 555:584 celery insoluble dietary fiber (CIDF) 555:591 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 61 theme celery 555:560 arg1 CIDF 587:590 CIDF 587:590 CIDF 587:590 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 5 62 theme % 766:766 arg1 DSS 797:799 3% Dextran sulfate sodium salt (DSS) 765:800 METHODS 3% Dextran sulfate sodium salt (DSS) 757:800 METHODS 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. 36693567 5 63 theme sulfate 776:782 arg1 DSS 797:799 3% Dextran sulfate sodium salt (DSS) 765:800 METHODS 3% Dextran sulfate sodium salt (DSS) 757:800 METHODS 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. 36693567 8 64 theme MPO/iNOS 1279:1286 arg1 activities 1288:1297 colonic MPO/iNOS activities 1271:1297 colonic MPO/iNOS activities 1271:1297 Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. 36693567 1 65 theme inflammatory 216:227 arg1 IBD 244:246 IBD 244:246 IBD 244:246 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 1 65 theme inflammatory 216:227 arg1 disease 235:241 inflammatory bowel disease 216:241 inflammatory bowel disease (IBD) 216:247 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 12 66 theme celery 1884:1889 arg1 food 1897:1900 celery whole food 1884:1900 celery whole food 1884:1900 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 6 67 theme molecular 850:858 arg1 methods 871:877 Multiple molecular biological methods 841:877 Multiple molecular biological methods 841:877 Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. 36693567 1 68 theme disease 235:241 arg1 treatment 203:211 the treatment 199:211 the treatment of inflammatory bowel disease (IBD) 199:247 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 7 69 from length 1081:1086 arg1 mice 1099:1102 colonic mice 1091:1102 colonic mice 1091:1102 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 4 70 theme celery 594:599 arg1 CF 613:614 CF 613:614 CF 613:614 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 70 theme celery 594:599 arg1 flavonoids 601:610 celery flavonoids 594:610 celery flavonoids (CF) 594:615 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 1 71 theme Dietary 138:144 arg1 flavonoids 156:165 flavonoids 156:165 flavonoids 156:165 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 1 71 theme Dietary 138:144 arg1 drugs 181:185 promising drugs 171:185 promising drugs reported in the treatment of inflammatory bowel disease (IBD) 171:247 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 1 71 theme Dietary 138:144 arg1 fiber 146:150 ***Introduction Dietary fiber 122:150 ***Introduction Dietary fiber 122:150 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 12 72 theme antagonistic 2184:2195 arg1 effect 2197:2202 an antagonistic effect 2181:2202 an antagonistic effect 2181:2202 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 4 73 theme IBD 641:643 arg1 model 650:654 IBD mice model 641:654 IBD mice model 641:654 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 74 theme component 720:728 arg1 s 730:730 component(s) 720:731 which component(s) in such complex matrix 714:754 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 6 75 theme mice 921:924 arg1 colitis 926:932 mice colitis 921:932 mice colitis 921:932 Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. 36693567 0 76 theme dextran-sodium-sulfate-induced 74:103 arg1 colitis 105:111 dextran-sodium-sulfate-induced colitis 74:111 dextran-sodium-sulfate-induced colitis in mice 74:119 Celery soluble dietary fiber antagonize flavonoids ameliorative effect on dextran-sodium-sulfate-induced colitis in mice. 36693567 5 77 used used 806:809 arg2 METHODS 757:763 METHODS 3% Dextran sulfate sodium salt (DSS) 757:800 METHODS 3% Dextran sulfate sodium salt (DSS) 757:800 METHODS 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. 36693567 5 78 theme salt 791:794 arg1 DSS 797:799 3% Dextran sulfate sodium salt (DSS) 765:800 METHODS 3% Dextran sulfate sodium salt (DSS) 757:800 METHODS 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. 36693567 4 79 theme CSDF+CF 618:624 arg1 efficacy 492:499 the efficacy 488:499 the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model 488:654 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 12 80 dep CONCLUSIONS 1687:1697 arg1 revealed 1710:1717 revealed 1710:1717 revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 1710:2203 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 7 81 theme colonic 1091:1097 arg1 mice 1099:1102 colonic mice 1091:1102 colonic mice 1091:1102 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 4 82 theme whole 504:508 arg1 celery 510:515 whole celery 504:515 whole celery 504:515 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 83 theme CIDF+CF 630:636 arg1 efficacy 492:499 the efficacy 488:499 the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model 488:654 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 0 84 from effect 64:69 arg1 colitis 105:111 dextran-sodium-sulfate-induced colitis 74:111 dextran-sodium-sulfate-induced colitis in mice 74:119 Celery soluble dietary fiber antagonize flavonoids ameliorative effect on dextran-sodium-sulfate-induced colitis in mice. 36693567 12 85 theme dietary 2114:2120 arg1 fiber 2122:2126 dietary fiber 2114:2126 dietary fiber 2114:2126 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 12 86 theme intestinal 1792:1801 arg1 health 1803:1808 intestinal health 1792:1808 intestinal health 1792:1808 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 9 87 theme weaker 1347:1352 arg1 improvement 1354:1364 weaker improvement 1347:1364 weaker improvement than CF or SDF in most physical and biochemical signs 1347:1418 However, CSDF+CF showed weaker improvement than CF or SDF in most physical and biochemical signs. 36693567 6 88 theme mice 971:974 arg1 severity 909:916 the severity 905:916 the severity of mice colitis 905:932 Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. 36693567 6 88 theme mice 971:974 arg1 composition 956:966 the gut microbial composition 938:966 the gut microbial composition of mice 938:974 Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. 36693567 3 89 theme therapeutic 355:365 arg1 effect 367:372 The therapeutic effect 351:372 The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages 351:459 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 7 90 from score 1064:1068 arg1 mice 1099:1102 colonic mice 1091:1102 colonic mice 1091:1102 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 0 91 theme soluble 7:13 arg1 fiber 23:27 Celery soluble dietary fiber 0:27 Celery soluble dietary fiber 0:27 Celery soluble dietary fiber antagonize flavonoids ameliorative effect on dextran-sodium-sulfate-induced colitis in mice. 36693567 5 92 theme mice 821:824 arg1 model 834:838 mice colitis model 821:838 mice colitis model 821:838 METHODS 3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. 36693567 4 93 theme fiber 541:545 arg1 efficacy 492:499 the efficacy 488:499 the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model 488:654 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 8 94 theme mucus 1241:1245 arg1 expression 1247:1256 colonic mucus expression 1233:1256 colonic mucus expression 1233:1256 Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. 36693567 3 95 theme colitis 418:424 arg1 mice 426:429 colitis mice 418:429 colitis mice using non-group feeding cages 418:459 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 1 96 theme *** 122:124 arg1 Introduction 125:136 Introduction 125:136 Introduction 125:136 ***Introduction Dietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). 36693567 6 97 theme gut 942:944 arg1 composition 956:966 the gut microbial composition 938:966 the gut microbial composition of mice 938:974 Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice. 36693567 12 98 theme flavonoids 2131:2140 arg1 efficacy 2102:2109 the efficacy 2098:2109 the efficacy of dietary fiber or flavonoids 2098:2140 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 7 99 theme body 1047:1050 arg1 weight 1052:1057 body weight 1047:1057 body weight 1047:1057 RESULTS Administration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. 36693567 12 100 theme CF 1786:1787 arg1 effect 1776:1781 the protective effect 1761:1781 the protective effect of CF 1761:1787 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 12 101 theme first 2002:2006 arg1 time 2008:2011 the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect 1998:2202 the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect 1998:2202 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 3 102 theme powders 407:413 arg1 effect 367:372 The therapeutic effect 351:372 The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages 351:459 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 3 103 dep OBJECTIVE 341:349 arg1 investigated 465:476 investigated 465:476 was investigated 461:476 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 3 104 theme feeding 447:453 arg1 cages 455:459 non-group feeding cages 437:459 non-group feeding cages 437:459 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 11 105 dep promoted 1587:1594 arg1 inhibited 1668:1676 inhibited 1668:1676 can be inhibited by CSDF 1661:1684 Interestingly, celery flavonoid promoted g_Akkermansia proliferation both in vivo and in vitro, and which can be inhibited by CSDF. 36693567 12 106 from efficacy 1872:1879 arg1 colitis 1905:1911 colitis 1905:1911 colitis 1905:1911 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 3 107 theme red 395:397 arg1 powders 407:413 red chicory powders 395:413 red chicory powders 395:413 OBJECTIVE The therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. 36693567 4 108 theme soluble 525:531 arg1 fiber 541:545 celery soluble dietary fiber 518:545 celery soluble dietary fiber (CSDF) 518:552 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 108 theme soluble 525:531 arg1 CSDF 548:551 CSDF 548:551 CSDF 548:551 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 109 theme such 736:739 arg1 matrix 749:754 such complex matrix 736:754 such complex matrix 736:754 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 4 110 theme fiber 580:584 arg1 efficacy 492:499 the efficacy 488:499 the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model 488:654 Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF+CF and CIDF+CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix. 36693567 12 111 theme soluble 2038:2044 arg1 fiber 2054:2058 soluble dietary fiber 2038:2058 soluble dietary fiber 2038:2058 CONCLUSIONS This study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect. 36693567 2 112 theme gut 329:331 arg1 health 333:338 gut health 329:338 gut health 329:338 However, it is unclear the interaction between dietary fiber and flavonoids in gut health. 36693567 8 113 theme IL-6/IL-1β 1304:1313 arg1 levels 1315:1320 IL-6/IL-1β levels 1304:1320 IL-6/IL-1β levels 1304:1320 Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. 36837835 9 0 theme qRT-PCR 1509:1515 arg1 test 1517:1520 qRT-PCR test 1509:1520 qRT-PCR test 1509:1520 qRT-PCR test further proved that the gene expression level was consistent with the results of RNA sequence data. 36837835 10 1 theme related 1781:1787 arg1 genes 1775:1779 functional genes 1764:1779 functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L 1764:1857 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 6 2 theme total 1154:1158 arg1 ability 1169:1175 the total reducing ability 1150:1175 the total reducing ability 1150:1175 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 2 3 theme HSK 304:306 arg1 composition 289:299 the chemical composition 276:299 the chemical composition of HSK 276:306 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 2 3 theme HSK 304:306 arg1 complex 322:328 complex 322:328 complex 322:328 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 5 4 from rutin 909:913 arg1 flowers 922:928 HSK flowers 918:928 HSK flowers 918:928 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 2 5 theme tumor 530:534 arg1 cells 536:540 tumor cells 530:540 tumor cells 530:540 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 6 6 theme antioxidant 1062:1072 arg1 strongest 1129:1137 strongest 1129:1137 strongest 1129:1137 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 6 6 theme antioxidant 1062:1072 arg1 capacity 1074:1081 the antioxidant capacity 1058:1081 the antioxidant capacity of the T3 flower alcohol extract 1058:1114 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 10 7 dep mining 1739:1744 arg1 the 1735:1737 the 1735:1737 the 1735:1737 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 5 8 from stage 936:940 arg1 content 850:856 The total content 840:856 The total content of flavonoids 840:870 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 8 from stage 936:940 arg1 higher 977:982 higher 977:982 higher 977:982 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 8 from stage 936:940 arg1 hyperoside 893:902 hyperoside 893:902 hyperoside 893:902 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 8 from stage 936:940 arg1 rutin 909:913 rutin 909:913 rutin 909:913 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 8 from stage 936:940 arg1 rhamnoside 881:890 vitexin rhamnoside 873:890 vitexin rhamnoside 873:890 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 2 9 with flavonoids 353:362 arg1 effects 434:440 good effects 429:440 good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells 429:540 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 7 10 theme flavonoids 1270:1279 arg1 total 1257:1261 A total 1255:1261 A total of 156 flavonoids and 47,179 unigenes 1255:1299 A total of 156 flavonoids and 47,179 unigenes were detected by UPLC-MS/MS and RNA-Seq, respectively. 36837835 3 11 theme flavonoid 643:651 arg1 extraction 653:662 the flavonoid extraction and determining method 639:685 extraction 653:662 In this experiment, different developmental stages of HSK flowers were used for optimization of the flavonoid extraction and determining method. 36837835 9 12 theme gene 1546:1549 arg1 level 1562:1566 the gene expression level 1542:1566 the gene expression level 1542:1566 qRT-PCR test further proved that the gene expression level was consistent with the results of RNA sequence data. 36837835 10 13 dep biosynthesis 1806:1817 arg1 the 1792:1794 the 1792:1794 the 1792:1794 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 1 14 theme rare 172:175 arg1 species 192:198 a rare and endangered species 170:198 a rare and endangered species in the wild that grows on the cliffs of deep mountains 170:253 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 1 14 theme rare 172:175 arg1 L 158:158 Abelmoschus manihot L 138:158 Abelmoschus manihot L. (HSK) 138:165 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 3 15 theme method 680:685 arg1 optimization 623:634 optimization 623:634 optimization of the flavonoid extraction and determining method 623:685 In this experiment, different developmental stages of HSK flowers were used for optimization of the flavonoid extraction and determining method. 36837835 1 16 theme endangered 181:190 arg1 species 192:198 a rare and endangered species 170:198 a rare and endangered species in the wild that grows on the cliffs of deep mountains 170:253 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 1 16 theme endangered 181:190 arg1 L 158:158 Abelmoschus manihot L 138:158 Abelmoschus manihot L. (HSK) 138:165 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 10 17 from biosynthesis 1806:1817 arg1 L 1857:1857 Abelmoschus manihot L 1837:1857 Abelmoschus manihot L 1837:1857 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 2 18 theme analgesic 484:492 arg1 nerves 507:512 anti-inflammatory, analgesic, and calming nerves 465:512 anti-inflammatory, analgesic, and calming nerves 465:512 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 2 18 theme analgesic 484:492 arg1 heat 459:462 heat 459:462 away heat 454:462 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 5 19 theme full 996:999 arg1 T2 992:993 T2 992:993 T2 (full flowering) 992:1010 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 19 theme full 996:999 arg1 flowering 1001:1009 full flowering 996:1009 full flowering 996:1009 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 10 20 theme flavonoid 1671:1679 arg1 accumulation 1681:1692 flavonoid accumulation 1671:1692 flavonoid accumulation 1671:1692 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 1 21 from species 192:198 arg1 wild 207:210 wild 207:210 wild 207:210 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 10 22 from metabolism 1823:1832 arg1 L 1857:1857 Abelmoschus manihot L 1837:1857 Abelmoschus manihot L 1837:1857 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 6 23 theme alcohol 1100:1106 arg1 extract 1108:1114 the T3 flower alcohol extract 1086:1114 the T3 flower alcohol extract 1086:1114 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 6 24 theme DPPH 1178:1181 arg1 clearance 1183:1191 DPPH clearance 1178:1191 DPPH clearance 1178:1191 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 10 25 theme expression 1656:1665 arg1 network 1694:1700 the gene expression and flavonoid accumulation network 1647:1700 the gene expression and flavonoid accumulation network 1647:1700 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 6 26 theme T3 1090:1091 arg1 extract 1108:1114 the T3 flower alcohol extract 1086:1114 the T3 flower alcohol extract 1086:1114 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 7 27 theme 47,179 1285:1290 arg1 unigenes 1292:1299 47,179 unigenes 1285:1299 47,179 unigenes 1285:1299 A total of 156 flavonoids and 47,179 unigenes were detected by UPLC-MS/MS and RNA-Seq, respectively. 36837835 1 28 theme manihot 150:156 arg1 species 192:198 a rare and endangered species 170:198 a rare and endangered species in the wild that grows on the cliffs of deep mountains 170:253 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 1 28 theme manihot 150:156 arg1 L 158:158 Abelmoschus manihot L 138:158 Abelmoschus manihot L. (HSK) 138:165 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 1 28 theme manihot 150:156 arg1 HSK 162:164 HSK 162:164 HSK 162:164 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 1 29 theme Abelmoschus 138:148 arg1 species 192:198 a rare and endangered species 170:198 a rare and endangered species in the wild that grows on the cliffs of deep mountains 170:253 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 1 29 theme Abelmoschus 138:148 arg1 L 158:158 Abelmoschus manihot L 138:158 Abelmoschus manihot L. (HSK) 138:165 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 1 29 theme Abelmoschus 138:148 arg1 HSK 162:164 HSK 162:164 HSK 162:164 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 9 30 theme sequence 1607:1614 arg1 data 1616:1619 RNA sequence data 1603:1619 RNA sequence data 1603:1619 qRT-PCR test further proved that the gene expression level was consistent with the results of RNA sequence data. 36837835 5 31 theme total 844:848 arg1 content 850:856 The total content 840:856 The total content of flavonoids 840:870 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 31 theme total 844:848 arg1 higher 977:982 higher 977:982 higher 977:982 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 2 32 theme calming 499:505 arg1 nerves 507:512 anti-inflammatory, analgesic, and calming nerves 465:512 anti-inflammatory, analgesic, and calming nerves 465:512 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 2 32 theme calming 499:505 arg1 heat 459:462 heat 459:462 away heat 454:462 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 6 33 theme total 1227:1231 arg1 capacity 1245:1252 total antioxidant capacity 1227:1252 total antioxidant capacity 1227:1252 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 5 34 from content 850:856 arg1 flowers 922:928 HSK flowers 918:928 HSK flowers 918:928 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 2 35 theme anti-inflammatory 465:481 arg1 nerves 507:512 anti-inflammatory, analgesic, and calming nerves 465:512 anti-inflammatory, analgesic, and calming nerves 465:512 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 2 35 theme anti-inflammatory 465:481 arg1 heat 459:462 heat 459:462 away heat 454:462 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 8 36 theme candidate 1360:1368 arg1 genes 1370:1374 candidate genes 1360:1374 candidate genes 1360:1374 The candidate genes and key metabolites involved in flavonoid biosynthesis were identified and the regulatory networks were also analyzed in this study. 36837835 0 37 theme L. 105:106 arg1 Mechanism 72:80 the Flavonoid Biosynthesis Mechanism 45:80 the Flavonoid Biosynthesis Mechanism of Abelmoschus manihot L. 45:106 Transcriptome and Metabolome Analysis Reveal the Flavonoid Biosynthesis Mechanism of Abelmoschus manihot L. at Different Anthesis Stages. 36837835 4 38 theme accumulation 726:737 arg1 pattern 739:745 flavonoid accumulation pattern 716:745 flavonoid accumulation pattern 716:745 The antioxidant activities, flavonoid accumulation pattern, and synthesis regulatory network were analyzed using biochemistry, RNA-seq, and UPLC-MS/MS. 36837835 0 39 theme Different 111:119 arg1 Stages 130:135 Different Anthesis Stages 111:135 Different Anthesis Stages 111:135 Transcriptome and Metabolome Analysis Reveal the Flavonoid Biosynthesis Mechanism of Abelmoschus manihot L. at Different Anthesis Stages. 36837835 0 40 theme Transcriptome 0:12 arg1 Analysis 29:36 Transcriptome and Metabolome Analysis 0:36 Analysis 29:36 Transcriptome and Metabolome Analysis Reveal the Flavonoid Biosynthesis Mechanism of Abelmoschus manihot L. at Different Anthesis Stages. 36837835 1 41 theme deep 240:243 arg1 mountains 245:253 deep mountains 240:253 deep mountains 240:253 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 4 42 theme antioxidant 692:702 arg1 activities 704:713 The antioxidant activities 688:713 The antioxidant activities 688:713 The antioxidant activities, flavonoid accumulation pattern, and synthesis regulatory network were analyzed using biochemistry, RNA-seq, and UPLC-MS/MS. 36837835 9 43 with consistent 1572:1581 arg1 results 1592:1598 the results 1588:1598 the results of RNA sequence data 1588:1619 qRT-PCR test further proved that the gene expression level was consistent with the results of RNA sequence data. 36837835 0 44 theme Metabolome 18:27 arg1 Analysis 29:36 Transcriptome and Metabolome Analysis 0:36 Analysis 29:36 Transcriptome and Metabolome Analysis Reveal the Flavonoid Biosynthesis Mechanism of Abelmoschus manihot L. at Different Anthesis Stages. 36837835 5 45 theme wilting 950:956 arg1 stage 936:940 T3 stage 933:940 T3 stage (flower wilting) 933:957 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 45 theme wilting 950:956 arg1 flower 943:948 flower wilting 943:956 flower wilting 943:956 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 2 46 theme trace 409:413 arg1 elements 415:422 various trace elements 401:422 various trace elements 401:422 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 3 47 theme developmental 573:585 arg1 stages 587:592 different developmental stages 563:592 different developmental stages of HSK flowers 563:607 In this experiment, different developmental stages of HSK flowers were used for optimization of the flavonoid extraction and determining method. 36837835 0 48 theme Flavonoid 49:57 arg1 Mechanism 72:80 the Flavonoid Biosynthesis Mechanism 45:80 the Flavonoid Biosynthesis Mechanism of Abelmoschus manihot L. 45:106 Transcriptome and Metabolome Analysis Reveal the Flavonoid Biosynthesis Mechanism of Abelmoschus manihot L. at Different Anthesis Stages. 36837835 2 49 theme chemical 280:287 arg1 composition 289:299 the chemical composition 276:299 the chemical composition of HSK 276:306 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 2 49 theme chemical 280:287 arg1 complex 322:328 complex 322:328 complex 322:328 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 5 50 theme T3 933:934 arg1 stage 936:940 T3 stage 933:940 T3 stage (flower wilting) 933:957 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 50 theme T3 933:934 arg1 flower 943:948 flower wilting 943:956 flower wilting 943:956 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 3 51 theme flowers 601:607 arg1 stages 587:592 different developmental stages 563:592 different developmental stages of HSK flowers 563:607 In this experiment, different developmental stages of HSK flowers were used for optimization of the flavonoid extraction and determining method. 36837835 4 52 theme synthesis 752:760 arg1 network 773:779 synthesis regulatory network 752:779 synthesis regulatory network 752:779 The antioxidant activities, flavonoid accumulation pattern, and synthesis regulatory network were analyzed using biochemistry, RNA-seq, and UPLC-MS/MS. 36837835 5 53 from hyperoside 893:902 arg1 flowers 922:928 HSK flowers 918:928 HSK flowers 918:928 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 6 54 theme reducing 1160:1167 arg1 ability 1169:1175 the total reducing ability 1150:1175 the total reducing ability 1150:1175 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 10 55 theme flavonoid 1796:1804 arg1 biosynthesis 1806:1817 flavonoid biosynthesis 1796:1817 flavonoid biosynthesis 1796:1817 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 8 56 dep genes 1370:1374 arg1 The 1356:1358 The 1356:1358 The 1356:1358 The candidate genes and key metabolites involved in flavonoid biosynthesis were identified and the regulatory networks were also analyzed in this study. 36837835 10 57 theme genes 1775:1779 arg1 regulation 1750:1759 regulation 1750:1759 regulation 1750:1759 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 10 57 theme genes 1775:1779 arg1 mining 1739:1744 mining 1739:1744 mining 1739:1744 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 7 58 theme unigenes 1292:1299 arg1 total 1257:1261 A total 1255:1261 A total of 156 flavonoids and 47,179 unigenes 1255:1299 A total of 156 flavonoids and 47,179 unigenes were detected by UPLC-MS/MS and RNA-Seq, respectively. 36837835 3 59 theme determining 668:678 arg1 method 680:685 the flavonoid extraction and determining method 639:685 method 680:685 In this experiment, different developmental stages of HSK flowers were used for optimization of the flavonoid extraction and determining method. 36837835 2 60 with acids 373:377 arg1 effects 434:440 good effects 429:440 good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells 429:540 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 3 61 used used 614:617 arg2 stages 587:592 different developmental stages 563:592 different developmental stages of HSK flowers 563:607 In this experiment, different developmental stages of HSK flowers were used for optimization of the flavonoid extraction and determining method. 36837835 3 62 theme extraction 653:662 arg1 optimization 623:634 optimization 623:634 optimization of the flavonoid extraction and determining method 623:685 In this experiment, different developmental stages of HSK flowers were used for optimization of the flavonoid extraction and determining method. 36837835 10 63 theme gene 1651:1654 arg1 expression 1656:1665 gene expression 1651:1665 gene expression 1651:1665 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 9 64 theme expression 1551:1560 arg1 level 1562:1566 the gene expression level 1542:1566 the gene expression level 1542:1566 qRT-PCR test further proved that the gene expression level was consistent with the results of RNA sequence data. 36837835 7 65 theme 156 1266:1268 arg1 flavonoids 1270:1279 156 flavonoids 1266:1279 156 flavonoids 1266:1279 A total of 156 flavonoids and 47,179 unigenes were detected by UPLC-MS/MS and RNA-Seq, respectively. 36837835 10 66 theme manihot 1849:1855 arg1 L 1857:1857 Abelmoschus manihot L 1837:1857 Abelmoschus manihot L 1837:1857 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 2 67 theme natural 261:267 arg1 plant 269:273 a natural plant 259:273 a natural plant 259:273 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 10 68 dep expression 1656:1665 arg1 the 1647:1649 the 1647:1649 the 1647:1649 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 6 69 theme OH 1194:1195 arg1 clearance 1197:1205 OH clearance 1194:1205 OH clearance 1194:1205 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 10 70 theme accumulation 1681:1692 arg1 network 1694:1700 the gene expression and flavonoid accumulation network 1647:1700 the gene expression and flavonoid accumulation network 1647:1700 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 6 71 theme extract 1108:1114 arg1 strongest 1129:1137 strongest 1129:1137 strongest 1129:1137 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 6 71 theme extract 1108:1114 arg1 capacity 1074:1081 the antioxidant capacity 1058:1081 the antioxidant capacity of the T3 flower alcohol extract 1058:1114 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 5 72 theme flavonoids 861:870 arg1 content 850:856 The total content 840:856 The total content of flavonoids 840:870 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 72 theme flavonoids 861:870 arg1 higher 977:982 higher 977:982 higher 977:982 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 72 theme flavonoids 861:870 arg1 hyperoside 893:902 hyperoside 893:902 hyperoside 893:902 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 72 theme flavonoids 861:870 arg1 rutin 909:913 rutin 909:913 rutin 909:913 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 5 72 theme flavonoids 861:870 arg1 rhamnoside 881:890 vitexin rhamnoside 873:890 vitexin rhamnoside 873:890 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 6 73 theme flower 1093:1098 arg1 extract 1108:1114 the T3 flower alcohol extract 1086:1114 the T3 flower alcohol extract 1086:1114 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 10 74 theme theoretical 1713:1723 arg1 basis 1725:1729 a theoretical basis 1711:1729 a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L 1711:1857 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 5 75 theme vitexin 873:879 arg1 rhamnoside 881:890 vitexin rhamnoside 873:890 vitexin rhamnoside 873:890 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 9 76 theme RNA 1603:1605 arg1 data 1616:1619 RNA sequence data 1603:1619 RNA sequence data 1603:1619 qRT-PCR test further proved that the gene expression level was consistent with the results of RNA sequence data. 36837835 9 77 theme data 1616:1619 arg1 results 1592:1598 the results 1588:1598 the results of RNA sequence data 1588:1619 qRT-PCR test further proved that the gene expression level was consistent with the results of RNA sequence data. 36837835 6 78 theme antioxidant 1233:1243 arg1 capacity 1245:1252 total antioxidant capacity 1227:1252 total antioxidant capacity 1227:1252 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 10 79 theme Abelmoschus 1837:1847 arg1 L 1857:1857 Abelmoschus manihot L 1837:1857 Abelmoschus manihot L 1837:1857 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 2 80 with elements 415:422 arg1 effects 434:440 good effects 429:440 good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells 429:540 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 2 81 theme good 429:432 arg1 effects 434:440 good effects 429:440 good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells 429:540 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 8 82 theme key 1380:1382 arg1 metabolites 1384:1394 key metabolites 1380:1394 key metabolites 1380:1394 The candidate genes and key metabolites involved in flavonoid biosynthesis were identified and the regulatory networks were also analyzed in this study. 36837835 0 83 theme Anthesis 121:128 arg1 Stages 130:135 Different Anthesis Stages 111:135 Different Anthesis Stages 111:135 Transcriptome and Metabolome Analysis Reveal the Flavonoid Biosynthesis Mechanism of Abelmoschus manihot L. at Different Anthesis Stages. 36837835 5 84 theme HSK 918:920 arg1 flowers 922:928 HSK flowers 918:928 HSK flowers 918:928 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 4 85 theme flavonoid 716:724 arg1 pattern 739:745 flavonoid accumulation pattern 716:745 flavonoid accumulation pattern 716:745 The antioxidant activities, flavonoid accumulation pattern, and synthesis regulatory network were analyzed using biochemistry, RNA-seq, and UPLC-MS/MS. 36837835 5 86 from rhamnoside 881:890 arg1 flowers 922:928 HSK flowers 918:928 HSK flowers 918:928 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36837835 8 87 theme flavonoid 1408:1416 arg1 biosynthesis 1418:1429 flavonoid biosynthesis 1408:1429 flavonoid biosynthesis 1408:1429 The candidate genes and key metabolites involved in flavonoid biosynthesis were identified and the regulatory networks were also analyzed in this study. 36837835 1 88 theme mountains 245:253 arg1 cliffs 230:235 the cliffs 226:235 the cliffs of deep mountains 226:253 Abelmoschus manihot L. (HSK) is a rare and endangered species in the wild that grows on the cliffs of deep mountains. 36837835 2 89 theme organic 365:371 arg1 acids 373:377 organic acids 365:377 organic acids 365:377 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 3 90 theme different 563:571 arg1 stages 587:592 different developmental stages 563:592 different developmental stages of HSK flowers 563:607 In this experiment, different developmental stages of HSK flowers were used for optimization of the flavonoid extraction and determining method. 36837835 4 91 theme regulatory 762:771 arg1 network 773:779 synthesis regulatory network 752:779 synthesis regulatory network 752:779 The antioxidant activities, flavonoid accumulation pattern, and synthesis regulatory network were analyzed using biochemistry, RNA-seq, and UPLC-MS/MS. 36837835 6 92 theme O2- 1208:1210 arg1 clearance 1212:1220 O2- clearance 1208:1220 O2- clearance 1208:1220 Compared with T1 and T2, the antioxidant capacity of the T3 flower alcohol extract was also the strongest, including the total reducing ability, DPPH clearance, OH clearance, O2- clearance, and total antioxidant capacity. 36837835 0 93 theme Biosynthesis 59:70 arg1 Mechanism 72:80 the Flavonoid Biosynthesis Mechanism 45:80 the Flavonoid Biosynthesis Mechanism of Abelmoschus manihot L. 45:106 Transcriptome and Metabolome Analysis Reveal the Flavonoid Biosynthesis Mechanism of Abelmoschus manihot L. at Different Anthesis Stages. 36837835 2 94 theme various 401:407 arg1 elements 415:422 various trace elements 401:422 various trace elements 401:422 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 8 95 theme regulatory 1455:1464 arg1 networks 1466:1473 the regulatory networks 1451:1473 the regulatory networks 1451:1473 The candidate genes and key metabolites involved in flavonoid biosynthesis were identified and the regulatory networks were also analyzed in this study. 36837835 10 96 theme functional 1764:1773 arg1 genes 1775:1779 functional genes 1764:1779 functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L 1764:1857 The relationship between the gene expression and flavonoid accumulation network provides a theoretical basis for the mining and regulation of functional genes related to the flavonoid biosynthesis and metabolism in Abelmoschus manihot L. 36837835 3 97 theme HSK 597:599 arg1 flowers 601:607 HSK flowers 597:607 HSK flowers 597:607 In this experiment, different developmental stages of HSK flowers were used for optimization of the flavonoid extraction and determining method. 36837835 2 98 with polysaccharides 380:394 arg1 effects 434:440 good effects 429:440 good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells 429:540 As a natural plant, the chemical composition of HSK is relatively complex, which mainly includes flavonoids, organic acids, polysaccharides, and various trace elements with good effects of clearing away heat, anti-inflammatory, analgesic, and calming nerves, and inhibiting tumor cells. 36837835 5 99 dep T2 992:993 arg1 stages 1025:1030 stages 1025:1030 stages 1025:1030 The total content of flavonoids, vitexin rhamnoside, hyperoside, and rutin in HSK flowers at T3 stage (flower wilting) was significantly higher than in T2 (full flowering) and T1 (bud) stages. 36204065 0 0 from secretion 15:23 arg1 Chlamydomonas 67:79 Chlamydomonas reinhardtii 67:91 Chlamydomonas reinhardtii 67:91 Production and secretion of functional SARS-CoV-2 spike protein in Chlamydomonas reinhardtii. 36204065 4 1 theme SARS-CoV-2 520:529 arg1 protein 537:543 full-length SARS-CoV-2 spike protein 508:543 full-length SARS-CoV-2 spike protein 508:543 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 1 2 theme coronaviruses 151:163 arg1 surface 140:146 the surface 136:146 the surface of coronaviruses 136:163 The spike protein is the major protein on the surface of coronaviruses. 36204065 0 3 from Production 0:9 arg1 Chlamydomonas 67:79 Chlamydomonas reinhardtii 67:91 Chlamydomonas reinhardtii 67:91 Production and secretion of functional SARS-CoV-2 spike protein in Chlamydomonas reinhardtii. 36204065 4 4 theme secreted 593:600 arg1 protein 602:608 a secreted protein 591:608 a secreted protein 591:608 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 3 5 theme N-linked 367:374 arg1 glycans 376:382 22 N-linked glycans 364:382 22 N-linked glycans 364:382 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 7 6 theme GRAS 1137:1140 arg1 reinhardtii 1120:1130 Chlamydomonas reinhardtii 1106:1130 Chlamydomonas reinhardtii 1106:1130 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 7 6 theme GRAS 1137:1140 arg1 organism 1142:1149 a GRAS organism 1135:1149 a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries 1135:1345 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 7 7 theme attractive 1233:1242 arg1 platform 1255:1262 an attractive production platform 1230:1262 an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries 1230:1345 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 2 8 theme vaccines 285:292 arg1 antigen 251:257 the antigen 247:257 the antigen of all currently admitted vaccines against SARS-CoV-2 247:311 It is therefore the prominent target of neutralizing antibodies and consequently the antigen of all currently admitted vaccines against SARS-CoV-2. 36204065 2 8 theme vaccines 285:292 arg1 antibodies 219:228 antibodies 219:228 antibodies 219:228 It is therefore the prominent target of neutralizing antibodies and consequently the antigen of all currently admitted vaccines against SARS-CoV-2. 36204065 2 9 theme admitted 276:283 arg1 vaccines 285:292 all currently admitted vaccines 262:292 all currently admitted vaccines against SARS-CoV-2 262:311 It is therefore the prominent target of neutralizing antibodies and consequently the antigen of all currently admitted vaccines against SARS-CoV-2. 36204065 5 10 theme cleavage 882:889 arg1 site 891:894 the multi-basic cleavage site 866:894 the multi-basic cleavage site 866:894 We show that the spike protein is efficiently cleaved at the furin cleavage site during synthesis in the alga and that cleavage is abolished upon mutation of the multi-basic cleavage site. 36204065 4 11 theme alga 676:679 arg1 reinhardtii 695:705 the unicellular green alga Chlamydomonas reinhardtii 654:705 the unicellular green alga Chlamydomonas reinhardtii 654:705 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 0 12 theme spike 50:54 arg1 protein 56:62 functional SARS-CoV-2 spike protein 28:62 functional SARS-CoV-2 spike protein 28:62 Production and secretion of functional SARS-CoV-2 spike protein in Chlamydomonas reinhardtii. 36204065 1 13 from protein 125:131 arg1 surface 140:146 the surface 136:146 the surface of coronaviruses 136:163 The spike protein is the major protein on the surface of coronaviruses. 36204065 3 14 link N-linked 367:374 arg1 glycans 376:382 22 N-linked glycans 364:382 22 N-linked glycans 364:382 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 4 15 theme green 670:674 arg1 reinhardtii 695:705 the unicellular green alga Chlamydomonas reinhardtii 654:705 the unicellular green alga Chlamydomonas reinhardtii 654:705 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 4 16 from anchor 579:584 arg1 conformation 638:649 the prefusion-stabilized conformation 613:649 the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii 613:705 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 6 17 theme sulfate 963:969 arg1 precipitation 971:983 ammonium sulfate precipitation 954:983 ammonium sulfate precipitation 954:983 We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. 36204065 5 18 theme furin 769:773 arg1 site 784:787 the furin cleavage site 765:787 the furin cleavage site 765:787 We show that the spike protein is efficiently cleaved at the furin cleavage site during synthesis in the alga and that cleavage is abolished upon mutation of the multi-basic cleavage site. 36204065 6 19 theme human 1088:1092 arg1 cells 1099:1103 human 293T cells 1088:1103 human 293T cells 1088:1103 We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. 36204065 3 20 theme spike 427:431 arg1 protein 433:439 functional, full-length spike protein 403:439 protein 433:439 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 5 21 from synthesis 796:804 arg1 alga 813:816 the alga 809:816 the alga 809:816 We show that the spike protein is efficiently cleaved at the furin cleavage site during synthesis in the alga and that cleavage is abolished upon mutation of the multi-basic cleavage site. 36204065 4 22 theme C-terminal 559:568 arg1 anchor 579:584 the C-terminal membrane anchor - 555:586 the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii 555:705 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 7 23 theme Chlamydomonas 1106:1118 arg1 reinhardtii 1120:1130 Chlamydomonas reinhardtii 1106:1130 Chlamydomonas reinhardtii 1106:1130 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 7 23 theme Chlamydomonas 1106:1118 arg1 organism 1142:1149 a GRAS organism 1135:1149 a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries 1135:1345 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 4 24 theme full-length 508:518 arg1 protein 537:543 full-length SARS-CoV-2 spike protein 508:543 full-length SARS-CoV-2 spike protein 508:543 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 1 25 theme spike 98:102 arg1 protein 125:131 the major protein 115:131 the major protein on the surface of coronaviruses 115:163 The spike protein is the major protein on the surface of coronaviruses. 36204065 1 25 theme spike 98:102 arg1 protein 104:110 The spike protein 94:110 The spike protein 94:110 The spike protein is the major protein on the surface of coronaviruses. 36204065 3 26 theme protein 433:439 arg1 production 389:398 the production 385:398 the production of functional, full-length spike protein 385:439 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 7 27 theme low 1177:1179 arg1 cost 1181:1184 low cost 1177:1184 low cost 1177:1184 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 6 28 theme 293T 1094:1097 arg1 cells 1099:1103 human 293T cells 1088:1103 human 293T cells 1088:1103 We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. 36204065 7 29 from protein 1286:1292 arg1 countries 1337:1345 low-income countries 1326:1345 low-income countries 1326:1345 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 6 30 with interaction 1032:1042 arg1 ACE2 1070:1073 ACE2 1070:1073 ACE2 1070:1073 We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. 36204065 6 30 with interaction 1032:1042 arg1 ACE2 1061:1064 recombinant ACE2 1049:1064 recombinant ACE2 1049:1064 We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. 36204065 5 31 theme spike 725:729 arg1 protein 731:737 the spike protein 721:737 the spike protein 721:737 We show that the spike protein is efficiently cleaved at the furin cleavage site during synthesis in the alga and that cleavage is abolished upon mutation of the multi-basic cleavage site. 36204065 4 32 from conformation 638:649 arg1 reinhardtii 695:705 the unicellular green alga Chlamydomonas reinhardtii 654:705 the unicellular green alga Chlamydomonas reinhardtii 654:705 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 0 33 theme SARS-CoV-2 39:48 arg1 protein 56:62 functional SARS-CoV-2 spike protein 28:62 functional SARS-CoV-2 spike protein 28:62 Production and secretion of functional SARS-CoV-2 spike protein in Chlamydomonas reinhardtii. 36204065 4 34 theme membrane 570:577 arg1 anchor 579:584 the C-terminal membrane anchor - 555:586 the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii 555:705 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 7 35 theme simple 1189:1194 arg1 media 1196:1200 simple media 1189:1200 simple media 1189:1200 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 3 36 with glycoprotein 346:357 arg1 glycans 376:382 22 N-linked glycans 364:382 22 N-linked glycans 364:382 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 4 37 theme Chlamydomonas 681:693 arg1 reinhardtii 695:705 the unicellular green alga Chlamydomonas reinhardtii 654:705 the unicellular green alga Chlamydomonas reinhardtii 654:705 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 4 38 theme unicellular 658:668 arg1 reinhardtii 695:705 the unicellular green alga Chlamydomonas reinhardtii 654:705 the unicellular green alga Chlamydomonas reinhardtii 654:705 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 0 39 theme functional 28:37 arg1 protein 56:62 functional SARS-CoV-2 spike protein 28:62 functional SARS-CoV-2 spike protein 28:62 Production and secretion of functional SARS-CoV-2 spike protein in Chlamydomonas reinhardtii. 36204065 4 40 theme protein 537:543 arg1 production 494:503 the production 490:503 the production of full-length SARS-CoV-2 spike protein 490:543 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 3 41 gly glycoprotein 346:357 arg1 glycoprotein 346:357 a 1,273-amino acids glycoprotein 326:357 a 1,273-amino acids glycoprotein with 22 N-linked glycans 326:382 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 3 41 gly glycoprotein 346:357 arg1 it 320:321 it 320:321 it 320:321 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 3 42 theme higher 456:461 arg1 eukaryotes 463:472 higher eukaryotes 456:472 higher eukaryotes 456:472 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 0 43 theme protein 56:62 arg1 secretion 15:23 secretion 15:23 secretion 15:23 Production and secretion of functional SARS-CoV-2 spike protein in Chlamydomonas reinhardtii. 36204065 0 43 theme protein 56:62 arg1 Production 0:9 Production 0:9 Production 0:9 Production and secretion of functional SARS-CoV-2 spike protein in Chlamydomonas reinhardtii. 36204065 4 44 theme spike 531:535 arg1 protein 537:543 full-length SARS-CoV-2 spike protein 508:543 full-length SARS-CoV-2 spike protein 508:543 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 6 45 from medium 944:949 arg1 protein 923:929 the spike protein 913:929 the spike protein from culture medium by ammonium sulfate precipitation 913:983 We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. 36204065 5 46 theme cleavage 775:782 arg1 site 784:787 the furin cleavage site 765:787 the furin cleavage site 765:787 We show that the spike protein is efficiently cleaved at the furin cleavage site during synthesis in the alga and that cleavage is abolished upon mutation of the multi-basic cleavage site. 36204065 7 47 theme spike 1280:1284 arg1 protein 1286:1292 recombinant spike protein 1268:1292 recombinant spike protein 1268:1292 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 3 48 theme functional 403:412 arg1 protein 433:439 functional, full-length spike protein 403:439 protein 433:439 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 6 49 theme spike 917:921 arg1 protein 923:929 the spike protein 913:929 the spike protein from culture medium by ammonium sulfate precipitation 913:983 We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. 36204065 7 50 from biopharmaceuticals 1304:1321 arg1 countries 1337:1345 low-income countries 1326:1345 low-income countries 1326:1345 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 1 51 theme major 119:123 arg1 protein 125:131 the major protein 115:131 the major protein on the surface of coronaviruses 115:163 The spike protein is the major protein on the surface of coronaviruses. 36204065 1 51 theme major 119:123 arg1 protein 104:110 The spike protein 94:110 The spike protein 94:110 The spike protein is the major protein on the surface of coronaviruses. 36204065 6 52 theme culture 936:942 arg1 medium 944:949 culture medium 936:949 culture medium 936:949 We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. 36204065 6 53 theme ammonium 954:961 arg1 precipitation 971:983 ammonium sulfate precipitation 954:983 ammonium sulfate precipitation 954:983 We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. 36204065 5 54 theme site 891:894 arg1 mutation 854:861 mutation 854:861 mutation of the multi-basic cleavage site 854:894 We show that the spike protein is efficiently cleaved at the furin cleavage site during synthesis in the alga and that cleavage is abolished upon mutation of the multi-basic cleavage site. 36204065 6 55 theme recombinant 1049:1059 arg1 ACE2 1061:1064 recombinant ACE2 1049:1064 recombinant ACE2 1049:1064 We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. 36204065 2 56 theme prominent 186:194 arg1 target 196:201 the prominent target 182:201 the prominent target of neutralizing antibodies and consequently the antigen of all currently admitted vaccines against SARS-CoV-2 182:311 It is therefore the prominent target of neutralizing antibodies and consequently the antigen of all currently admitted vaccines against SARS-CoV-2. 36204065 2 56 theme prominent 186:194 arg1 It 166:167 It 166:167 It 166:167 It is therefore the prominent target of neutralizing antibodies and consequently the antigen of all currently admitted vaccines against SARS-CoV-2. 36204065 7 57 theme recombinant 1268:1278 arg1 protein 1286:1292 recombinant spike protein 1268:1292 recombinant spike protein 1268:1292 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 7 58 theme low-income 1326:1335 arg1 countries 1337:1345 low-income countries 1326:1345 low-income countries 1326:1345 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 3 59 theme 1,273-amino 328:338 arg1 glycoprotein 346:357 a 1,273-amino acids glycoprotein 326:357 a 1,273-amino acids glycoprotein with 22 N-linked glycans 326:382 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 3 59 theme 1,273-amino 328:338 arg1 it 320:321 it 320:321 it 320:321 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 7 60 theme other 1298:1302 arg1 biopharmaceuticals 1304:1321 other biopharmaceuticals 1298:1321 other biopharmaceuticals in low-income countries 1298:1345 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 7 61 theme production 1244:1253 arg1 platform 1255:1262 an attractive production platform 1230:1262 an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries 1230:1345 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36204065 5 62 theme multi-basic 870:880 arg1 site 891:894 the multi-basic cleavage site 866:894 the multi-basic cleavage site 866:894 We show that the spike protein is efficiently cleaved at the furin cleavage site during synthesis in the alga and that cleavage is abolished upon mutation of the multi-basic cleavage site. 36204065 4 63 theme prefusion-stabilized 617:636 arg1 conformation 638:649 the prefusion-stabilized conformation 613:649 the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii 613:705 Here we report the production of full-length SARS-CoV-2 spike protein - lacking the C-terminal membrane anchor - as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. 36204065 3 64 theme acids 340:344 arg1 glycoprotein 346:357 a 1,273-amino acids glycoprotein 326:357 a 1,273-amino acids glycoprotein with 22 N-linked glycans 326:382 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 3 64 theme acids 340:344 arg1 it 320:321 it 320:321 it 320:321 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 3 65 theme full-length 415:425 arg1 protein 433:439 functional, full-length spike protein 403:439 protein 433:439 Since it is a 1,273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to higher eukaryotes. 36204065 7 66 theme large 1207:1211 arg1 scale 1213:1217 a large scale 1205:1217 a large scale 1205:1217 Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries. 36911209 3 0 theme synthetic 312:320 arg1 scheme 322:327 our original synthetic scheme 299:327 our original synthetic scheme 299:327 We have further optimized our original synthetic scheme by increasing the selectivity of azidonitration of the galactal derivative and developing a one-pot Büchner-Curtius-Schlotterbeck reaction. 36911209 5 1 theme intermediate 660:671 arg1 synthesis 639:647 a gram-scale synthesis 626:647 a gram-scale synthesis of the key intermediate 12 626:674 In this article, we describe detailed procedures for a gram-scale synthesis of the key intermediate 12 and synthesizing 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide. 36911209 1 2 theme cancer 153:158 arg1 fields 173:178 cancer biochemistry fields 153:178 cancer biochemistry fields 153:178 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 8 3 theme Büchner-Curtius-Schlotterbeck 1054:1082 arg1 procedure 1099:1107 Büchner-Curtius-Schlotterbeck (BCS) reaction procedure 1054:1107 Büchner-Curtius-Schlotterbeck (BCS) reaction procedure for the tunicamycin core structure 1054:1142 •Optimized Büchner-Curtius-Schlotterbeck (BCS) reaction procedure for the tunicamycin core structure. 36911209 1 4 theme biochemistry 160:171 arg1 fields 173:178 cancer biochemistry fields 153:178 cancer biochemistry fields 153:178 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 5 5 from D-galctal-4,5-acetonide 749:771 arg1 100 mg 693:698 100 mg 693:698 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide 693:771 In this article, we describe detailed procedures for a gram-scale synthesis of the key intermediate 12 and synthesizing 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide. 36911209 4 6 theme V 549:549 arg1 synthesis 524:532 the synthesis 520:532 the synthesis of tunicamycin V in 33% overall yield 520:570 An improved synthetic scheme reported here enables the synthesis of tunicamycin V in 33% overall yield. 36911209 8 7 theme BCS 1085:1087 arg1 procedure 1099:1107 Büchner-Curtius-Schlotterbeck (BCS) reaction procedure 1054:1107 Büchner-Curtius-Schlotterbeck (BCS) reaction procedure for the tunicamycin core structure 1054:1142 •Optimized Büchner-Curtius-Schlotterbeck (BCS) reaction procedure for the tunicamycin core structure. 36911209 9 8 from detail 1150:1155 arg1 synthesis 1181:1189 the 15-chemical step synthesis 1160:1189 the 15-chemical step synthesis of tunicamycin V 1160:1206 •Full detail on the 15-chemical step synthesis of tunicamycin V. 36911209 3 9 theme azidonitration 362:375 arg1 selectivity 347:357 the selectivity 343:357 the selectivity of azidonitration of the galactal derivative 343:402 We have further optimized our original synthetic scheme by increasing the selectivity of azidonitration of the galactal derivative and developing a one-pot Büchner-Curtius-Schlotterbeck reaction. 36911209 7 10 dep 3aR,4R,7aR 868:877 arg1 pyran-4-yl 929:938 pyran-4-yl 929:938 pyran-4-yl 929:938 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 7 10 dep 3aR,4R,7aR 868:877 arg1 dioxolo[4,5-c 915:927 dioxolo[4,5-c 915:927 dioxolo[4,5-c 915:927 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 7 10 dep 3aR,4R,7aR 868:877 arg1 -2,2-dimethyl-3a,7a-dihydro-4H-[1,3 879:913 -2,2-dimethyl-3a,7a-dihydro-4H-[1,3 879:913 -2,2-dimethyl-3a,7a-dihydro-4H-[1,3 879:913 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 1 11 from misfolding 139:148 arg1 fields 173:178 cancer biochemistry fields 153:178 cancer biochemistry fields 153:178 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 9 12 theme V 1206:1206 arg1 synthesis 1181:1189 the 15-chemical step synthesis 1160:1189 the 15-chemical step synthesis of tunicamycin V 1160:1206 •Full detail on the 15-chemical step synthesis of tunicamycin V. 36911209 7 13 theme acetamide 947:955 arg1 azidonitration 845:858 •Highly selective azidonitration 827:858 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) 827:981 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 5 14 theme detailed 602:609 arg1 procedures 611:620 detailed procedures 602:620 detailed procedures for a gram-scale synthesis of the key intermediate 12 602:674 In this article, we describe detailed procedures for a gram-scale synthesis of the key intermediate 12 and synthesizing 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide. 36911209 4 15 from synthesis 524:532 arg1 yield 566:570 33% overall yield 554:570 33% overall yield 554:570 An improved synthetic scheme reported here enables the synthesis of tunicamycin V in 33% overall yield. 36911209 5 16 theme gram-scale 628:637 arg1 synthesis 639:647 a gram-scale synthesis 626:647 a gram-scale synthesis of the key intermediate 12 626:674 In this article, we describe detailed procedures for a gram-scale synthesis of the key intermediate 12 and synthesizing 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide. 36911209 7 17 dep acetamide 947:955 arg1 3aR,4R,7aR 868:877 3aR,4R,7aR 868:877 3aR,4R,7aR 868:877 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 9 18 theme 15-chemical 1164:1174 arg1 synthesis 1181:1189 the 15-chemical step synthesis 1160:1189 the 15-chemical step synthesis of tunicamycin V 1160:1206 •Full detail on the 15-chemical step synthesis of tunicamycin V. 36911209 8 19 theme reaction 1090:1097 arg1 procedure 1099:1107 Büchner-Curtius-Schlotterbeck (BCS) reaction procedure 1054:1107 Büchner-Curtius-Schlotterbeck (BCS) reaction procedure for the tunicamycin core structure 1054:1142 •Optimized Büchner-Curtius-Schlotterbeck (BCS) reaction procedure for the tunicamycin core structure. 36911209 1 20 theme important 67:75 arg1 tools 89:93 important biochemical tools 67:93 important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields 67:178 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 1 20 theme important 67:75 arg1 tunicamycins 50:61 The tunicamycins 46:61 The tunicamycins 46:61 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 9 21 theme step 1176:1179 arg1 synthesis 1181:1189 the 15-chemical step synthesis 1160:1189 the 15-chemical step synthesis of tunicamycin V 1160:1206 •Full detail on the 15-chemical step synthesis of tunicamycin V. 36911209 3 22 theme galactal 384:391 arg1 derivative 393:402 the galactal derivative 380:402 the galactal derivative 380:402 We have further optimized our original synthetic scheme by increasing the selectivity of azidonitration of the galactal derivative and developing a one-pot Büchner-Curtius-Schlotterbeck reaction. 36911209 8 23 theme core 1129:1132 arg1 structure 1134:1142 the tunicamycin core structure 1113:1142 the tunicamycin core structure 1113:1142 •Optimized Büchner-Curtius-Schlotterbeck (BCS) reaction procedure for the tunicamycin core structure. 36911209 6 24 theme multiple 812:819 arg1 times 821:825 repeated multiple times 803:825 repeated multiple times 803:825 All chemical steps have been repeated multiple times. 36911209 1 25 theme biochemical 77:87 arg1 tools 89:93 important biochemical tools 67:93 important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields 67:178 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 1 25 theme biochemical 77:87 arg1 tunicamycins 50:61 The tunicamycins 46:61 The tunicamycins 46:61 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 3 26 theme Büchner-Curtius-Schlotterbeck 429:457 arg1 reaction 459:466 a one-pot Büchner-Curtius-Schlotterbeck reaction 419:466 a one-pot Büchner-Curtius-Schlotterbeck reaction 419:466 We have further optimized our original synthetic scheme by increasing the selectivity of azidonitration of the galactal derivative and developing a one-pot Büchner-Curtius-Schlotterbeck reaction. 36911209 3 27 theme derivative 393:402 arg1 azidonitration 362:375 azidonitration 362:375 azidonitration of the galactal derivative 362:402 We have further optimized our original synthetic scheme by increasing the selectivity of azidonitration of the galactal derivative and developing a one-pot Büchner-Curtius-Schlotterbeck reaction. 36911209 7 28 theme selective 835:843 arg1 azidonitration 845:858 •Highly selective azidonitration 827:858 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) 827:981 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 5 29 theme key 656:658 arg1 intermediate 660:671 the key intermediate 12 652:674 the key intermediate 12 652:674 In this article, we describe detailed procedures for a gram-scale synthesis of the key intermediate 12 and synthesizing 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide. 36911209 6 30 theme repeated 803:810 arg1 times 821:825 repeated multiple times 803:825 repeated multiple times 803:825 All chemical steps have been repeated multiple times. 36911209 1 31 gly glycosylation 113:125 arg1 fields 173:178 cancer biochemistry fields 153:178 cancer biochemistry fields 153:178 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 1 32 from glycosylation 113:125 arg1 fields 173:178 cancer biochemistry fields 153:178 cancer biochemistry fields 153:178 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 9 33 theme tunicamycin 1194:1204 arg1 V 1206:1206 tunicamycin V 1194:1206 tunicamycin V 1194:1206 •Full detail on the 15-chemical step synthesis of tunicamycin V. 36911209 0 34 theme total 12:16 arg1 synthesis 18:26 total synthesis 12:26 total synthesis of tunicamycin V 12:43 An improved total synthesis of tunicamycin V. 36911209 4 35 theme synthetic 481:489 arg1 scheme 491:496 An improved synthetic scheme 469:496 An improved synthetic scheme reported here 469:510 An improved synthetic scheme reported here enables the synthesis of tunicamycin V in 33% overall yield. 36911209 2 36 with synthesis 206:214 arg1 yield 250:254 21% overall yield 238:254 21% overall yield from D-galactal 238:270 We reported a convergent synthesis of tunicamycin V with 21% overall yield from D-galactal. 36911209 7 37 theme 2-azido-2-deoxy-α/β-D-galactopyranoside 991:1029 arg1 derivatives 1031:1041 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives 991:1041 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives 991:1041 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 0 38 theme tunicamycin 31:41 arg1 V 43:43 tunicamycin V 31:43 tunicamycin V 31:43 An improved total synthesis of tunicamycin V. 36911209 4 39 theme improved 472:479 arg1 scheme 491:496 An improved synthetic scheme 469:496 An improved synthetic scheme reported here 469:510 An improved synthetic scheme reported here enables the synthesis of tunicamycin V in 33% overall yield. 36911209 2 40 theme 21 238:239 arg1 % 240:240 % 240:240 % 240:240 We reported a convergent synthesis of tunicamycin V with 21% overall yield from D-galactal. 36911209 7 41 theme N- 863:864 arg1 D-galctal-4,5-acetonide 958:980 D-galctal-4,5-acetonide 958:980 D-galctal-4,5-acetonide 958:980 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 7 41 theme N- 863:864 arg1 acetamide 947:955 N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide 863:955 N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) 863:981 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 3 42 theme one-pot 421:427 arg1 reaction 459:466 a one-pot Büchner-Curtius-Schlotterbeck reaction 419:466 a one-pot Büchner-Curtius-Schlotterbeck reaction 419:466 We have further optimized our original synthetic scheme by increasing the selectivity of azidonitration of the galactal derivative and developing a one-pot Büchner-Curtius-Schlotterbeck reaction. 36911209 4 43 theme % 556:556 arg1 yield 566:570 33% overall yield 554:570 33% overall yield 554:570 An improved synthetic scheme reported here enables the synthesis of tunicamycin V in 33% overall yield. 36911209 4 44 theme 33 554:555 arg1 % 556:556 % 556:556 % 556:556 An improved synthetic scheme reported here enables the synthesis of tunicamycin V in 33% overall yield. 36911209 2 45 theme V 231:231 arg1 synthesis 206:214 a convergent synthesis 193:214 a convergent synthesis of tunicamycin V with 21% overall yield from D-galactal 193:270 We reported a convergent synthesis of tunicamycin V with 21% overall yield from D-galactal. 36911209 5 46 theme tunicamycin 703:713 arg1 1 718:718 1 718:718 1 718:718 In this article, we describe detailed procedures for a gram-scale synthesis of the key intermediate 12 and synthesizing 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide. 36911209 5 46 theme tunicamycin 703:713 arg1 V 715:715 tunicamycin V 703:715 tunicamycin V (1) 703:719 In this article, we describe detailed procedures for a gram-scale synthesis of the key intermediate 12 and synthesizing 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide. 36911209 1 47 theme N-linked 104:111 arg1 glycosylation 113:125 N-linked glycosylation 104:125 N-linked glycosylation 104:125 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 0 48 theme V 43:43 arg1 synthesis 18:26 total synthesis 12:26 total synthesis of tunicamycin V 12:43 An improved total synthesis of tunicamycin V. 36911209 3 49 theme original 303:310 arg1 scheme 322:327 our original synthetic scheme 299:327 our original synthetic scheme 299:327 We have further optimized our original synthetic scheme by increasing the selectivity of azidonitration of the galactal derivative and developing a one-pot Büchner-Curtius-Schlotterbeck reaction. 36911209 8 50 theme tunicamycin 1117:1127 arg1 structure 1134:1142 the tunicamycin core structure 1113:1142 the tunicamycin core structure 1113:1142 •Optimized Büchner-Curtius-Schlotterbeck (BCS) reaction procedure for the tunicamycin core structure. 36911209 2 51 theme tunicamycin 219:229 arg1 V 231:231 tunicamycin V 219:231 tunicamycin V 219:231 We reported a convergent synthesis of tunicamycin V with 21% overall yield from D-galactal. 36911209 6 52 theme chemical 778:785 arg1 steps 787:791 All chemical steps 774:791 All chemical steps 774:791 All chemical steps have been repeated multiple times. 36911209 4 53 theme overall 558:564 arg1 yield 566:570 33% overall yield 554:570 33% overall yield 554:570 An improved synthetic scheme reported here enables the synthesis of tunicamycin V in 33% overall yield. 36911209 1 54 link N-linked 104:111 arg1 glycosylation 113:125 N-linked glycosylation 104:125 N-linked glycosylation 104:125 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 2 55 from D-galactal 261:270 arg1 yield 250:254 21% overall yield 238:254 21% overall yield from D-galactal 238:270 We reported a convergent synthesis of tunicamycin V with 21% overall yield from D-galactal. 36911209 5 56 theme V 715:715 arg1 100 mg 693:698 100 mg 693:698 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide 693:771 In this article, we describe detailed procedures for a gram-scale synthesis of the key intermediate 12 and synthesizing 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide. 36911209 2 57 theme convergent 195:204 arg1 synthesis 206:214 a convergent synthesis 193:214 a convergent synthesis of tunicamycin V with 21% overall yield from D-galactal 193:270 We reported a convergent synthesis of tunicamycin V with 21% overall yield from D-galactal. 36911209 1 58 theme protein 131:137 arg1 misfolding 139:148 protein misfolding 131:148 protein misfolding 131:148 The tunicamycins are important biochemical tools to study N-linked glycosylation and protein misfolding in cancer biochemistry fields. 36911209 2 59 theme overall 242:248 arg1 yield 250:254 21% overall yield 238:254 21% overall yield from D-galactal 238:270 We reported a convergent synthesis of tunicamycin V with 21% overall yield from D-galactal. 36911209 7 60 theme methyl 940:945 arg1 D-galctal-4,5-acetonide 958:980 D-galctal-4,5-acetonide 958:980 D-galctal-4,5-acetonide 958:980 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 7 60 theme methyl 940:945 arg1 acetamide 947:955 N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide 863:955 N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) 863:981 •Highly selective azidonitration of N-(((3aR,4R,7aR)-2,2-dimethyl-3a,7a-dihydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl)acetamide (D-galctal-4,5-acetonide) to form 2-azido-2-deoxy-α/β-D-galactopyranoside derivatives. 36911209 4 61 theme tunicamycin 537:547 arg1 V 549:549 tunicamycin V 537:549 tunicamycin V 537:549 An improved synthetic scheme reported here enables the synthesis of tunicamycin V in 33% overall yield. 36911209 2 62 theme % 240:240 arg1 yield 250:254 21% overall yield 238:254 21% overall yield from D-galactal 238:270 We reported a convergent synthesis of tunicamycin V with 21% overall yield from D-galactal. 36911209 5 63 theme available 739:747 arg1 D-galctal-4,5-acetonide 749:771 commercially available D-galctal-4,5-acetonide 726:771 commercially available D-galctal-4,5-acetonide 726:771 In this article, we describe detailed procedures for a gram-scale synthesis of the key intermediate 12 and synthesizing 100 mg of tunicamycin V (1) from commercially available D-galctal-4,5-acetonide. 36480520 1 0 theme Mumps 138:142 arg1 agent 175:179 the etiological agent 159:179 the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications 159:301 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 1 0 theme Mumps 138:142 arg1 MuV 151:153 MuV 151:153 MuV 151:153 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 1 0 theme Mumps 138:142 arg1 virus 144:148 Mumps virus 138:148 Mumps virus (MuV) 138:154 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 6 1 link N-linked 1035:1042 arg1 glycosylation 1044:1056 complete N-linked glycosylation 1026:1056 complete N-linked glycosylation 1026:1056 In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein. 36480520 4 2 theme proteins 793:800 arg1 networks 772:779 comprehensive protein-protein interaction networks 730:779 comprehensive protein-protein interaction networks of the host proteins 730:800 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 5 3 theme immunoprecipitation 828:846 arg1 results 848:854 siRNA screening and immunoprecipitation results 808:854 results 848:854 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 0 4 theme virus 80:84 arg1 protein 93:99 mumps virus fusion protein 74:99 mumps virus fusion protein 74:99 SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation. 36480520 5 5 theme fusion 934:939 arg1 protein 945:951 the MuV fusion (F) protein 926:951 the MuV fusion (F) protein 926:951 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 5 6 theme F 942:942 arg1 protein 945:951 the MuV fusion (F) protein 926:951 the MuV fusion (F) protein 926:951 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 3 7 theme MuV 484:486 arg1 infection 488:496 MuV infection 484:496 MuV infection 484:496 However, little is known about the host factors involved in MuV infection, especially those involved in the late stage of infection. 36480520 1 8 theme painful 218:224 arg1 swelling 226:233 painful swelling 218:233 painful swelling of the parotid glands 218:255 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 0 9 theme mumps 74:78 arg1 virus 80:84 mumps virus 74:84 mumps virus fusion protein 74:99 SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation. 36480520 4 10 theme MuV 624:626 arg1 component 661:669 a major component 653:669 a major component of the viral particles 653:692 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 4 10 theme MuV 624:626 arg1 glycoproteins 628:640 MuV glycoproteins 624:640 MuV glycoproteins 624:640 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 0 11 theme protein 93:99 arg1 expression 60:69 the expression 56:69 the expression of mumps virus fusion protein 56:99 SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation. 36480520 0 11 theme protein 93:99 arg1 glycosylation 38:50 the glycosylation 34:50 the glycosylation 34:50 SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation. 36480520 0 12 theme fusion 86:91 arg1 protein 93:99 mumps virus fusion protein 74:99 mumps virus fusion protein 74:99 SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation. 36480520 0 13 theme SNARE 0:4 arg1 USE1 14:17 SNARE protein USE1 0:17 SNARE protein USE1 0:17 SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation. 36480520 2 14 theme infection 349:357 arg1 mechanism 332:340 the molecular mechanism 318:340 the molecular mechanism of MuV infection 318:357 To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. 36480520 0 15 theme protein 6:12 arg1 USE1 14:17 SNARE protein USE1 0:17 SNARE protein USE1 0:17 SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation. 36480520 4 16 theme host 788:791 arg1 proteins 793:800 the host proteins 784:800 the host proteins 784:800 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 4 17 theme major 655:659 arg1 component 661:669 a major component 653:669 a major component of the viral particles 653:692 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 4 17 theme major 655:659 arg1 glycoproteins 628:640 MuV glycoproteins 624:640 MuV glycoproteins 624:640 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 2 18 theme MuV 345:347 arg1 infection 349:357 MuV infection 345:357 MuV infection 345:357 To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. 36480520 2 19 theme host 398:401 arg1 factors 403:409 the involved host factors 385:409 the involved host factors 385:409 To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. 36480520 5 20 theme SNARE 873:877 arg1 USE1 898:901 USE1 898:901 USE1 898:901 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 5 20 theme SNARE 873:877 arg1 protein 889:895 a SNARE subfamily protein 871:895 a SNARE subfamily protein 871:895 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 5 20 theme SNARE 873:877 arg1 important 961:969 important 961:969 important 961:969 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 5 21 theme MuV 975:977 arg1 propagation 979:989 MuV propagation 975:989 MuV propagation 975:989 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 2 22 theme involved 389:396 arg1 factors 403:409 the involved host factors 385:409 the involved host factors 385:409 To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. 36480520 4 23 gly glycoproteins 628:640 arg1 component 661:669 a major component 653:669 a major component of the viral particles 653:692 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 4 23 gly glycoproteins 628:640 arg1 glycoproteins 628:640 MuV glycoproteins 624:640 MuV glycoproteins 624:640 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 5 24 theme subfamily 879:887 arg1 USE1 898:901 USE1 898:901 USE1 898:901 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 5 24 theme subfamily 879:887 arg1 protein 889:895 a SNARE subfamily protein 871:895 a SNARE subfamily protein 871:895 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 5 24 theme subfamily 879:887 arg1 important 961:969 important 961:969 important 961:969 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 4 25 theme comprehensive 730:742 arg1 networks 772:779 comprehensive protein-protein interaction networks 730:779 comprehensive protein-protein interaction networks of the host proteins 730:800 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 6 26 gly glycosylation 1044:1056 arg1 protein 1086:1092 the MuV F protein 1076:1092 the MuV F protein 1076:1092 In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein. 36480520 1 27 theme parotid 242:248 arg1 glands 250:255 the parotid glands 238:255 the parotid glands 238:255 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 6 28 theme MuV 1080:1082 arg1 protein 1086:1092 the MuV F protein 1076:1092 the MuV F protein 1076:1092 In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein. 36480520 6 29 theme complete 1026:1033 arg1 glycosylation 1044:1056 complete N-linked glycosylation 1026:1056 complete N-linked glycosylation 1026:1056 In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein. 36480520 1 30 theme etiological 163:173 arg1 agent 175:179 the etiological agent 159:179 the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications 159:301 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 1 30 theme etiological 163:173 arg1 virus 144:148 Mumps virus 138:148 Mumps virus (MuV) 138:154 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 1 31 theme glands 250:255 arg1 swelling 226:233 painful swelling 218:233 painful swelling of the parotid glands 218:255 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 0 32 theme viral 119:123 arg1 propagation 125:135 viral propagation 119:135 viral propagation 119:135 SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation. 36480520 1 33 dep disease 193:199 arg1 accompanied 267:277 accompanied 267:277 often accompanied by severe complications 261:301 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 1 33 dep disease 193:199 arg1 characterized 201:213 characterized 201:213 characterized by painful swelling of the parotid glands 201:255 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 3 34 theme late 532:535 arg1 stage 537:541 the late stage 528:541 the late stage of infection 528:554 However, little is known about the host factors involved in MuV infection, especially those involved in the late stage of infection. 36480520 5 35 theme siRNA 808:812 arg1 screening 814:822 siRNA screening and immunoprecipitation results 808:854 screening 814:822 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 2 36 theme functional 362:371 arg1 analysis 373:380 a functional analysis 360:380 a functional analysis of the involved host factors 360:409 To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. 36480520 5 37 theme MuV 930:932 arg1 protein 945:951 the MuV fusion (F) protein 926:951 the MuV fusion (F) protein 926:951 From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. 36480520 4 38 theme interaction 760:770 arg1 networks 772:779 comprehensive protein-protein interaction networks 730:779 comprehensive protein-protein interaction networks of the host proteins 730:800 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 4 39 theme protein-protein 744:758 arg1 networks 772:779 comprehensive protein-protein interaction networks 730:779 comprehensive protein-protein interaction networks of the host proteins 730:800 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 3 40 theme infection 546:554 arg1 stage 537:541 the late stage 528:541 the late stage of infection 528:554 However, little is known about the host factors involved in MuV infection, especially those involved in the late stage of infection. 36480520 4 41 contain have 600:603 arg1 proteins 586:593 638 host proteins 577:593 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling 577:715 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 4 41 contain have 600:603 arg2 proximity 611:619 close proximity 605:619 close proximity to MuV glycoproteins, which are a major component of the viral particles 605:692 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 4 42 theme proximity 698:706 arg1 labeling 708:715 proximity labeling 698:715 proximity labeling 698:715 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 4 43 theme close 605:609 arg1 proximity 611:619 close proximity 605:619 close proximity to MuV glycoproteins, which are a major component of the viral particles 605:692 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 6 44 theme N-linked 1035:1042 arg1 glycosylation 1044:1056 complete N-linked glycosylation 1026:1056 complete N-linked glycosylation 1026:1056 In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein. 36480520 1 45 theme mumps 184:188 arg1 agent 175:179 the etiological agent 159:179 the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications 159:301 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 1 45 theme mumps 184:188 arg1 virus 144:148 Mumps virus 138:148 Mumps virus (MuV) 138:154 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 4 46 theme particles 684:692 arg1 component 661:669 a major component 653:669 a major component of the viral particles 653:692 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 4 46 theme particles 684:692 arg1 glycoproteins 628:640 MuV glycoproteins 624:640 MuV glycoproteins 624:640 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 4 47 theme viral 678:682 arg1 particles 684:692 the viral particles 674:692 the viral particles 674:692 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 2 48 theme molecular 322:330 arg1 mechanism 332:340 the molecular mechanism 318:340 the molecular mechanism of MuV infection 318:357 To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. 36480520 6 49 theme F 1084:1084 arg1 protein 1086:1092 the MuV F protein 1076:1092 the MuV F protein 1076:1092 In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein. 36480520 6 50 theme protein 1086:1092 arg1 glycosylation 1044:1056 complete N-linked glycosylation 1026:1056 complete N-linked glycosylation 1026:1056 In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein. 36480520 6 50 theme protein 1086:1092 arg1 expression 1062:1071 expression 1062:1071 expression 1062:1071 In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein. 36480520 3 51 theme host 459:462 arg1 those 510:514 those 510:514 those 510:514 However, little is known about the host factors involved in MuV infection, especially those involved in the late stage of infection. 36480520 3 51 theme host 459:462 arg1 factors 464:470 the host factors 455:470 the host factors involved in MuV infection 455:496 However, little is known about the host factors involved in MuV infection, especially those involved in the late stage of infection. 36480520 4 52 theme host 581:584 arg1 proteins 586:593 638 host proteins 577:593 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling 577:715 Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. 36480520 1 53 theme severe 282:287 arg1 complications 289:301 severe complications 282:301 severe complications 282:301 Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. 36480520 0 54 gly glycosylation 38:50 arg1 protein 93:99 mumps virus fusion protein 74:99 mumps virus fusion protein 74:99 SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation. 36480520 2 55 theme factors 403:409 arg1 analysis 373:380 a functional analysis 360:380 a functional analysis of the involved host factors 360:409 To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. 36406079 0 0 theme mink 100:103 arg1 spermatogenesis 68:82 seasonal spermatogenesis 59:82 seasonal spermatogenesis of the American mink (Neovison vison) 59:120 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 36406079 4 1 theme chromatography-tandem 730:750 arg1 spectrometry 757:768 liquid chromatography-tandem mass spectrometry 723:768 liquid chromatography-tandem mass spectrometry analysis 723:777 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 5 2 theme canonical 829:837 arg1 motif 853:857 the canonical Asn-X-Ser/Thr motif 825:857 the canonical Asn-X-Ser/Thr motif 825:857 A total of 532 N-glycosylated sites matching the canonical Asn-X-Ser/Thr motif were identified in 357 testicular proteins. 36406079 7 3 theme testicular 1065:1074 arg1 proteins 1076:1083 testicular proteins 1065:1083 testicular proteins with different N-glycosylation 1065:1114 Functional analyses showed that testicular proteins with different N-glycosylation might play a vital role in spermatogenesis by affecting their folding, distribution, stability, and activity. 36406079 3 4 from function 416:423 arg1 spermatogenesis 464:478 seasonal spermatogenesis 455:478 seasonal spermatogenesis of the American mink 455:499 However, the function of protein N-glycosylation in seasonal spermatogenesis of the American mink remains unclear. 36406079 5 5 theme sites 810:814 arg1 total 782:786 A total 780:786 A total of 532 N-glycosylated sites matching the canonical Asn-X-Ser/Thr motif 780:857 A total of 532 N-glycosylated sites matching the canonical Asn-X-Ser/Thr motif were identified in 357 testicular proteins. 36406079 0 6 theme American 91:98 arg1 mink 100:103 the American mink 87:103 the American mink (Neovison vison) 87:120 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 36406079 0 6 theme American 91:98 arg1 vison 115:119 Neovison vison 106:119 Neovison vison 106:119 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 36406079 4 7 theme present 525:531 arg1 study 533:537 the present study 521:537 the present study 521:537 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 4 8 theme mass 752:755 arg1 spectrometry 757:768 liquid chromatography-tandem mass spectrometry 723:768 liquid chromatography-tandem mass spectrometry analysis 723:777 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 4 9 theme N-glycosylation 588:602 arg1 stoichiometry 571:583 a proteome-wide stoichiometry 555:583 a proteome-wide stoichiometry of N-glycosylation in mink testes 555:617 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 0 10 theme Neovison 106:113 arg1 mink 100:103 the American mink 87:103 the American mink (Neovison vison) 87:120 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 36406079 0 10 theme Neovison 106:113 arg1 vison 115:119 Neovison vison 106:119 Neovison vison 106:119 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 36406079 0 11 from Involvement 0:10 arg1 spermatogenesis 68:82 seasonal spermatogenesis 59:82 seasonal spermatogenesis of the American mink (Neovison vison) 59:120 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 36406079 8 12 gly N-glycosylation 1273:1287 arg1 proteins 1303:1310 testicular proteins 1292:1310 testicular proteins 1292:1310 Overall, our data suggest that the dynamics of N-glycosylation of testicular proteins are involved in seasonal spermatogenesis in the American mink. 36406079 4 13 theme spectrometry 757:768 arg1 analysis 770:777 liquid chromatography-tandem mass spectrometry analysis 723:777 liquid chromatography-tandem mass spectrometry analysis 723:777 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 3 14 theme mink 496:499 arg1 spermatogenesis 464:478 seasonal spermatogenesis 455:478 seasonal spermatogenesis of the American mink 455:499 However, the function of protein N-glycosylation in seasonal spermatogenesis of the American mink remains unclear. 36406079 5 15 theme N-glycosylated 795:808 arg1 sites 810:814 532 N-glycosylated sites 791:814 532 N-glycosylated sites matching the canonical Asn-X-Ser/Thr motif 791:857 A total of 532 N-glycosylated sites matching the canonical Asn-X-Ser/Thr motif were identified in 357 testicular proteins. 36406079 6 16 theme proteins 968:975 arg1 number 912:917 the number 908:917 the number of glycoproteins 908:934 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 16 theme proteins 968:975 arg1 proteins 968:975 N-glycosylated proteins 953:975 N-glycosylated proteins in mink testes 953:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 16 theme proteins 968:975 arg1 dynamic 1004:1010 dynamic 1004:1010 dynamic 1004:1010 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 16 theme proteins 968:975 arg1 glycoproteins 922:934 glycoproteins 922:934 glycoproteins 922:934 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 16 theme proteins 968:975 arg1 sites 944:948 the sites 940:948 the sites of N-glycosylated proteins in mink testes 940:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 4 17 theme spermatogenesis 640:654 arg1 phases 630:635 various phases 622:635 various phases of spermatogenesis 622:654 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 3 18 theme N-glycosylation 436:450 arg1 function 416:423 the function 412:423 the function of protein N-glycosylation in seasonal spermatogenesis of the American mink 412:499 However, the function of protein N-glycosylation in seasonal spermatogenesis of the American mink remains unclear. 36406079 4 19 theme mink 607:610 arg1 testes 612:617 mink testes 607:617 mink testes 607:617 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 6 20 theme N-glycosylated 953:966 arg1 proteins 968:975 N-glycosylated proteins 953:975 N-glycosylated proteins in mink testes 953:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 21 from proteins 968:975 arg1 testes 985:990 mink testes 980:990 mink testes 980:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 2 22 theme proteins 287:294 arg1 N-glycosylation 268:282 N-glycosylation 268:282 N-glycosylation of proteins 268:294 N-glycosylation of proteins has emerged as an important regulator as it affects protein folding, secretion, degradation, and activity. 36406079 2 23 gly N-glycosylation 268:282 arg1 proteins 287:294 proteins 287:294 proteins 287:294 N-glycosylation of proteins has emerged as an important regulator as it affects protein folding, secretion, degradation, and activity. 36406079 5 24 theme Asn-X-Ser/Thr 839:851 arg1 motif 853:857 the canonical Asn-X-Ser/Thr motif 825:857 the canonical Asn-X-Ser/Thr motif 825:857 A total of 532 N-glycosylated sites matching the canonical Asn-X-Ser/Thr motif were identified in 357 testicular proteins. 36406079 1 25 theme annual 183:188 arg1 cycle 190:194 an annual cycle 180:194 an annual cycle of transition involving completely inactive and fully activated stages 180:265 Spermatogenesis in the American mink is characterized by an annual cycle of transition involving completely inactive and fully activated stages. 36406079 4 26 from stoichiometry 571:583 arg1 testes 612:617 mink testes 607:617 mink testes 607:617 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 4 27 theme proteome-wide 557:569 arg1 stoichiometry 571:583 a proteome-wide stoichiometry 555:583 a proteome-wide stoichiometry of N-glycosylation in mink testes 555:617 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 8 28 theme seasonal 1328:1335 arg1 spermatogenesis 1337:1351 seasonal spermatogenesis 1328:1351 seasonal spermatogenesis in the American mink 1328:1372 Overall, our data suggest that the dynamics of N-glycosylation of testicular proteins are involved in seasonal spermatogenesis in the American mink. 36406079 7 29 with proteins 1076:1083 arg1 N-glycosylation 1100:1114 different N-glycosylation 1090:1114 different N-glycosylation 1090:1114 Functional analyses showed that testicular proteins with different N-glycosylation might play a vital role in spermatogenesis by affecting their folding, distribution, stability, and activity. 36406079 3 30 theme protein 428:434 arg1 N-glycosylation 436:450 protein N-glycosylation 428:450 protein N-glycosylation 428:450 However, the function of protein N-glycosylation in seasonal spermatogenesis of the American mink remains unclear. 36406079 0 31 theme N-glycoproteome 26:40 arg1 heterogeneity 42:54 testicular N-glycoproteome heterogeneity 15:54 testicular N-glycoproteome heterogeneity 15:54 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 36406079 5 32 theme testicular 882:891 arg1 proteins 893:900 357 testicular proteins 878:900 357 testicular proteins 878:900 A total of 532 N-glycosylated sites matching the canonical Asn-X-Ser/Thr motif were identified in 357 testicular proteins. 36406079 4 33 with combination 706:716 arg1 analysis 770:777 liquid chromatography-tandem mass spectrometry analysis 723:777 liquid chromatography-tandem mass spectrometry analysis 723:777 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 1 34 from Spermatogenesis 123:137 arg1 mink 155:158 the American mink 142:158 the American mink 142:158 Spermatogenesis in the American mink is characterized by an annual cycle of transition involving completely inactive and fully activated stages. 36406079 2 35 theme important 314:322 arg1 regulator 324:332 an important regulator 311:332 an important regulator as it affects protein folding, secretion, degradation, and activity 311:400 N-glycosylation of proteins has emerged as an important regulator as it affects protein folding, secretion, degradation, and activity. 36406079 8 36 theme American 1360:1367 arg1 mink 1369:1372 the American mink 1356:1372 the American mink 1356:1372 Overall, our data suggest that the dynamics of N-glycosylation of testicular proteins are involved in seasonal spermatogenesis in the American mink. 36406079 0 37 theme testicular 15:24 arg1 heterogeneity 42:54 testicular N-glycoproteome heterogeneity 15:54 testicular N-glycoproteome heterogeneity 15:54 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 36406079 4 38 theme various 622:628 arg1 phases 630:635 various phases 622:635 various phases of spermatogenesis 622:654 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 5 39 gly N-glycosylated 795:808 arg1 sites 810:814 532 N-glycosylated sites 791:814 532 N-glycosylated sites matching the canonical Asn-X-Ser/Thr motif 791:857 A total of 532 N-glycosylated sites matching the canonical Asn-X-Ser/Thr motif were identified in 357 testicular proteins. 36406079 6 40 gly glycoproteins 922:934 arg1 glycoproteins 922:934 glycoproteins 922:934 glycoproteins 922:934 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 1 41 theme transition 199:208 arg1 cycle 190:194 an annual cycle 180:194 an annual cycle of transition involving completely inactive and fully activated stages 180:265 Spermatogenesis in the American mink is characterized by an annual cycle of transition involving completely inactive and fully activated stages. 36406079 8 42 theme proteins 1303:1310 arg1 N-glycosylation 1273:1287 N-glycosylation 1273:1287 N-glycosylation of testicular proteins 1273:1310 Overall, our data suggest that the dynamics of N-glycosylation of testicular proteins are involved in seasonal spermatogenesis in the American mink. 36406079 4 43 theme glycosylated-peptide 671:690 arg1 enrichment 692:701 N-linked glycosylated-peptide enrichment 662:701 N-linked glycosylated-peptide enrichment 662:701 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 3 44 theme seasonal 455:462 arg1 spermatogenesis 464:478 seasonal spermatogenesis 455:478 seasonal spermatogenesis of the American mink 455:499 However, the function of protein N-glycosylation in seasonal spermatogenesis of the American mink remains unclear. 36406079 0 45 theme heterogeneity 42:54 arg1 Involvement 0:10 Involvement 0:10 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 0:121 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 36406079 8 46 theme testicular 1292:1301 arg1 proteins 1303:1310 testicular proteins 1292:1310 testicular proteins 1292:1310 Overall, our data suggest that the dynamics of N-glycosylation of testicular proteins are involved in seasonal spermatogenesis in the American mink. 36406079 6 47 from sites 944:948 arg1 testes 985:990 mink testes 980:990 mink testes 980:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 48 from number 912:917 arg1 testes 985:990 mink testes 980:990 mink testes 980:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 4 49 theme N-linked 662:669 arg1 enrichment 692:701 N-linked glycosylated-peptide enrichment 662:701 N-linked glycosylated-peptide enrichment 662:701 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 6 50 theme different 1015:1023 arg1 stages 1025:1030 different stages 1015:1030 different stages 1015:1030 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 51 theme glycoproteins 922:934 arg1 number 912:917 the number 908:917 the number of glycoproteins 908:934 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 51 theme glycoproteins 922:934 arg1 proteins 968:975 N-glycosylated proteins 953:975 N-glycosylated proteins in mink testes 953:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 51 theme glycoproteins 922:934 arg1 dynamic 1004:1010 dynamic 1004:1010 dynamic 1004:1010 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 51 theme glycoproteins 922:934 arg1 glycoproteins 922:934 glycoproteins 922:934 glycoproteins 922:934 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 51 theme glycoproteins 922:934 arg1 sites 944:948 the sites 940:948 the sites of N-glycosylated proteins in mink testes 940:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 8 52 from spermatogenesis 1337:1351 arg1 mink 1369:1372 the American mink 1356:1372 the American mink 1356:1372 Overall, our data suggest that the dynamics of N-glycosylation of testicular proteins are involved in seasonal spermatogenesis in the American mink. 36406079 0 53 theme seasonal 59:66 arg1 spermatogenesis 68:82 seasonal spermatogenesis 59:82 seasonal spermatogenesis of the American mink (Neovison vison) 59:120 Involvement of testicular N-glycoproteome heterogeneity in seasonal spermatogenesis of the American mink (Neovison vison). 36406079 7 54 gly N-glycosylation 1100:1114 arg1 proteins 1076:1083 testicular proteins 1065:1083 testicular proteins with different N-glycosylation 1065:1114 Functional analyses showed that testicular proteins with different N-glycosylation might play a vital role in spermatogenesis by affecting their folding, distribution, stability, and activity. 36406079 7 55 theme different 1090:1098 arg1 N-glycosylation 1100:1114 different N-glycosylation 1090:1114 different N-glycosylation 1090:1114 Functional analyses showed that testicular proteins with different N-glycosylation might play a vital role in spermatogenesis by affecting their folding, distribution, stability, and activity. 36406079 2 56 theme protein 348:354 arg1 folding 356:362 protein folding 348:362 protein folding 348:362 N-glycosylation of proteins has emerged as an important regulator as it affects protein folding, secretion, degradation, and activity. 36406079 6 57 from stages 1025:1030 arg1 number 912:917 the number 908:917 the number of glycoproteins 908:934 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 57 from stages 1025:1030 arg1 proteins 968:975 N-glycosylated proteins 953:975 N-glycosylated proteins in mink testes 953:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 57 from stages 1025:1030 arg1 dynamic 1004:1010 dynamic 1004:1010 dynamic 1004:1010 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 57 from stages 1025:1030 arg1 glycoproteins 922:934 glycoproteins 922:934 glycoproteins 922:934 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 57 from stages 1025:1030 arg1 sites 944:948 the sites 940:948 the sites of N-glycosylated proteins in mink testes 940:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 7 58 theme Functional 1033:1042 arg1 analyses 1044:1051 Functional analyses 1033:1051 Functional analyses 1033:1051 Functional analyses showed that testicular proteins with different N-glycosylation might play a vital role in spermatogenesis by affecting their folding, distribution, stability, and activity. 36406079 3 59 theme American 487:494 arg1 mink 496:499 the American mink 483:499 the American mink 483:499 However, the function of protein N-glycosylation in seasonal spermatogenesis of the American mink remains unclear. 36406079 1 60 theme inactive 231:238 arg1 stages 260:265 completely inactive and fully activated stages 220:265 completely inactive and fully activated stages 220:265 Spermatogenesis in the American mink is characterized by an annual cycle of transition involving completely inactive and fully activated stages. 36406079 7 61 theme vital 1129:1133 arg1 role 1135:1138 a vital role 1127:1138 a vital role 1127:1138 Functional analyses showed that testicular proteins with different N-glycosylation might play a vital role in spermatogenesis by affecting their folding, distribution, stability, and activity. 36406079 4 62 link N-linked 662:669 arg1 enrichment 692:701 N-linked glycosylated-peptide enrichment 662:701 N-linked glycosylated-peptide enrichment 662:701 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 2 63 dep regulator 324:332 arg1 affects 340:346 affects 340:346 affects protein folding, secretion, degradation, and activity 340:400 N-glycosylation of proteins has emerged as an important regulator as it affects protein folding, secretion, degradation, and activity. 36406079 6 64 from testes 985:990 arg1 number 912:917 the number 908:917 the number of glycoproteins 908:934 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 64 from testes 985:990 arg1 proteins 968:975 N-glycosylated proteins 953:975 N-glycosylated proteins in mink testes 953:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 64 from testes 985:990 arg1 dynamic 1004:1010 dynamic 1004:1010 dynamic 1004:1010 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 64 from testes 985:990 arg1 glycoproteins 922:934 glycoproteins 922:934 glycoproteins 922:934 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 64 from testes 985:990 arg1 sites 944:948 the sites 940:948 the sites of N-glycosylated proteins in mink testes 940:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 1 65 theme American 146:153 arg1 mink 155:158 the American mink 142:158 the American mink 142:158 Spermatogenesis in the American mink is characterized by an annual cycle of transition involving completely inactive and fully activated stages. 36406079 6 66 gly N-glycosylated 953:966 arg1 proteins 968:975 N-glycosylated proteins 953:975 N-glycosylated proteins in mink testes 953:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 6 67 theme mink 980:983 arg1 testes 985:990 mink testes 980:990 mink testes 980:990 Both the number of glycoproteins and the sites of N-glycosylated proteins in mink testes were highly dynamic at different stages. 36406079 8 68 theme N-glycosylation 1273:1287 arg1 dynamics 1261:1268 the dynamics 1257:1268 the dynamics of N-glycosylation of testicular proteins 1257:1310 Overall, our data suggest that the dynamics of N-glycosylation of testicular proteins are involved in seasonal spermatogenesis in the American mink. 36406079 4 69 theme liquid 723:728 arg1 spectrometry 757:768 liquid chromatography-tandem mass spectrometry 723:768 liquid chromatography-tandem mass spectrometry analysis 723:777 In the present study, we established a proteome-wide stoichiometry of N-glycosylation in mink testes at various phases of spermatogenesis using N-linked glycosylated-peptide enrichment in combination with liquid chromatography-tandem mass spectrometry analysis. 36406079 1 70 theme activated 250:258 arg1 stages 260:265 completely inactive and fully activated stages 220:265 completely inactive and fully activated stages 220:265 Spermatogenesis in the American mink is characterized by an annual cycle of transition involving completely inactive and fully activated stages. 35535043 2 0 with lots 407:410 arg1 date 482:485 an expiration date 468:485 an expiration date from 2020 to 2021 468:503 In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. 35535043 1 1 theme biosimilar 134:143 arg1 candidate 145:153 The proposed biosimilar candidate 121:153 The proposed biosimilar candidate 121:153 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 1 2 theme product 238:244 arg1 profile 246:252 target product profile 231:252 target product profile 231:252 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 0 3 theme Perjeta® 69:76 arg1 Variation 56:64 ADCC Potency Variation 43:64 ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China 43:118 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 1 4 theme extensive 335:343 arg1 characterization 345:360 extensive characterization 335:360 extensive characterization of the reference products 335:386 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 4 5 theme response 823:830 arg1 value 832:836 the maximum response value 811:836 the maximum response value 811:836 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 4 5 theme response 823:830 arg1 related 849:855 related 849:855 related 849:855 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 5 6 theme biosimilars 1035:1045 arg1 glycosylation 1001:1013 the glycosylation 997:1013 the glycosylation of Perjeta® and its biosimilars 997:1045 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 4 7 theme afucose 876:882 arg1 content 864:870 the content 860:870 the content of %afucose 860:882 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 0 8 from Drifts 0:5 arg1 Glycosylation 19:31 N-Linked Glycosylation 10:31 N-Linked Glycosylation 10:31 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 5 9 gly glycosylation 1001:1013 arg1 Perjeta® 1018:1025 Perjeta® 1018:1025 Perjeta® 1018:1025 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 5 9 gly glycosylation 1001:1013 arg1 biosimilars 1035:1045 its biosimilars 1031:1045 its biosimilars 1031:1045 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 4 10 theme effective 902:910 arg1 EC50 927:930 EC50 927:930 EC50 927:930 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 4 10 theme effective 902:910 arg1 concentration 912:924 half-maximal effective concentration 889:924 half-maximal effective concentration (EC50) 889:931 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 3 11 theme activity 702:709 arg1 variation 641:649 the variation 637:649 the variation of antibody-dependent cellular cytotoxicity (ADCC) activity 637:709 Despite the consistency of purity, drifts in N-glycan profile were observed, which resulted in the variation of antibody-dependent cellular cytotoxicity (ADCC) activity. 35535043 4 12 theme parametric 728:737 arg1 curves 739:744 four parametric curves 723:744 four parametric curves of ADCC activity of the reference product 723:786 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 1 13 theme biosimilarity 258:270 arg1 criteria 283:290 biosimilarity assessment criteria 258:290 biosimilarity assessment criteria 258:290 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 2 14 dep pertuzumab 429:438 arg1 trademark 441:449 trademark 441:449 trademark: Perjeta® 441:459 In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. 35535043 4 15 theme ADCC 749:752 arg1 activity 754:761 ADCC activity 749:761 ADCC activity of the reference product 749:786 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 1 16 theme reference 369:377 arg1 products 379:386 the reference products 365:386 the reference products 365:386 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 0 17 dep August 83:88 arg1 to 95:96 to 95:96 to 95:96 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 0 17 dep August 83:88 arg1 October 98:104 October 2021 98:109 August 2020 to October 2021 83:109 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 1 18 theme products 379:386 arg1 characterization 345:360 extensive characterization 335:360 extensive characterization of the reference products 335:386 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 2 19 dep trademark 441:449 arg1 Perjeta® 452:459 Perjeta® 452:459 trademark: Perjeta® 441:459 In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. 35535043 3 20 theme cellular 673:680 arg1 cytotoxicity 682:693 antibody-dependent cellular cytotoxicity 654:693 antibody-dependent cellular cytotoxicity (ADCC) activity 654:709 Despite the consistency of purity, drifts in N-glycan profile were observed, which resulted in the variation of antibody-dependent cellular cytotoxicity (ADCC) activity. 35535043 3 20 theme cellular 673:680 arg1 ADCC 696:699 ADCC 696:699 ADCC 696:699 Despite the consistency of purity, drifts in N-glycan profile were observed, which resulted in the variation of antibody-dependent cellular cytotoxicity (ADCC) activity. 35535043 3 21 theme antibody-dependent 654:671 arg1 cytotoxicity 682:693 antibody-dependent cellular cytotoxicity 654:693 antibody-dependent cellular cytotoxicity (ADCC) activity 654:709 Despite the consistency of purity, drifts in N-glycan profile were observed, which resulted in the variation of antibody-dependent cellular cytotoxicity (ADCC) activity. 35535043 3 21 theme antibody-dependent 654:671 arg1 ADCC 696:699 ADCC 696:699 ADCC 696:699 Despite the consistency of purity, drifts in N-glycan profile were observed, which resulted in the variation of antibody-dependent cellular cytotoxicity (ADCC) activity. 35535043 1 22 theme assessment 272:281 arg1 criteria 283:290 biosimilarity assessment criteria 258:290 biosimilarity assessment criteria 258:290 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 4 23 theme maximum 815:821 arg1 value 832:836 the maximum response value 811:836 the maximum response value 811:836 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 4 23 theme maximum 815:821 arg1 related 849:855 related 849:855 related 849:855 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 4 24 from detail 715:720 arg1 unparalleled 793:804 unparalleled 793:804 unparalleled 793:804 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 2 25 theme pertuzumab 429:438 arg1 lots 407:410 13 lots 404:410 13 lots 404:410 In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. 35535043 2 25 theme pertuzumab 429:438 arg1 pertuzumab 429:438 China-sourced pertuzumab 415:438 China-sourced pertuzumab (trademark: Perjeta®) 415:460 In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. 35535043 5 26 theme potential 947:955 arg1 attribute 974:982 a potential critical quality attribute 945:982 a potential critical quality attribute of Perjeta® 945:994 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 5 26 theme potential 947:955 arg1 ADCC 937:940 ADCC 937:940 ADCC 937:940 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 2 27 dep 2020 492:495 arg1 to 497:498 to 497:498 to 497:498 In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. 35535043 2 27 dep 2020 492:495 arg1 2021 500:503 2021 500:503 2021 500:503 In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. 35535043 5 28 theme Perjeta® 1018:1025 arg1 glycosylation 1001:1013 the glycosylation 997:1013 the glycosylation of Perjeta® and its biosimilars 997:1045 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 5 29 theme Perjeta® 987:994 arg1 attribute 974:982 a potential critical quality attribute 945:982 a potential critical quality attribute of Perjeta® 945:994 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 5 29 theme Perjeta® 987:994 arg1 ADCC 937:940 ADCC 937:940 ADCC 937:940 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 0 30 theme N-Linked 10:17 arg1 Glycosylation 19:31 N-Linked Glycosylation 10:31 N-Linked Glycosylation 10:31 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 4 31 theme % 875:875 arg1 afucose 876:882 %afucose 875:882 %afucose 875:882 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 1 32 dep quality 223:229 arg1 profile 246:252 target product profile 231:252 target product profile 231:252 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 1 33 theme reference 195:203 arg1 products 205:212 reference products 195:212 reference products 195:212 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 5 34 theme critical 957:964 arg1 attribute 974:982 a potential critical quality attribute 945:982 a potential critical quality attribute of Perjeta® 945:994 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 5 34 theme critical 957:964 arg1 ADCC 937:940 ADCC 937:940 ADCC 937:940 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 4 35 theme half-maximal 889:900 arg1 EC50 927:930 EC50 927:930 EC50 927:930 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 4 35 theme half-maximal 889:900 arg1 concentration 912:924 half-maximal effective concentration 889:924 half-maximal effective concentration (EC50) 889:931 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 5 36 theme quality 966:972 arg1 attribute 974:982 a potential critical quality attribute 945:982 a potential critical quality attribute of Perjeta® 945:994 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 5 36 theme quality 966:972 arg1 ADCC 937:940 ADCC 937:940 ADCC 937:940 As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled. 35535043 3 37 from drifts 577:582 arg1 profile 596:602 N-glycan profile 587:602 N-glycan profile 587:602 Despite the consistency of purity, drifts in N-glycan profile were observed, which resulted in the variation of antibody-dependent cellular cytotoxicity (ADCC) activity. 35535043 4 38 theme product 780:786 arg1 activity 754:761 ADCC activity 749:761 ADCC activity of the reference product 749:786 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 0 39 theme Potency 48:54 arg1 Variation 56:64 ADCC Potency Variation 43:64 ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China 43:118 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 0 40 from Variation 56:64 arg1 China 114:118 China 114:118 China 114:118 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 0 40 from Variation 56:64 arg1 August 83:88 August 83:88 August 83:88 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 4 41 from unparalleled 793:804 arg1 detail 715:720 detail 715:720 detail 715:720 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 0 42 theme ADCC 43:46 arg1 Variation 56:64 ADCC Potency Variation 43:64 ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China 43:118 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 1 43 with biosimilarity 176:188 arg1 products 205:212 reference products 195:212 reference products 195:212 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 2 44 from 2020 492:495 arg1 date 482:485 an expiration date 468:485 an expiration date from 2020 to 2021 468:503 In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. 35535043 3 45 theme purity 569:574 arg1 consistency 554:564 the consistency 550:564 the consistency of purity 550:574 Despite the consistency of purity, drifts in N-glycan profile were observed, which resulted in the variation of antibody-dependent cellular cytotoxicity (ADCC) activity. 35535043 3 46 theme N-glycan 587:594 arg1 profile 596:602 N-glycan profile 587:602 N-glycan profile 587:602 Despite the consistency of purity, drifts in N-glycan profile were observed, which resulted in the variation of antibody-dependent cellular cytotoxicity (ADCC) activity. 35535043 4 47 theme activity 754:761 arg1 curves 739:744 four parametric curves 723:744 four parametric curves of ADCC activity of the reference product 723:786 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 0 48 from August 83:88 arg1 Perjeta® 69:76 Perjeta® 69:76 Perjeta® from August 2020 to October 2021 69:109 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 0 48 from August 83:88 arg1 Variation 56:64 ADCC Potency Variation 43:64 ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China 43:118 Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China. 35535043 4 49 theme reference 770:778 arg1 product 780:786 the reference product 766:786 the reference product 766:786 In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). 35535043 2 50 theme expiration 471:480 arg1 date 482:485 an expiration date 468:485 an expiration date from 2020 to 2021 468:503 In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. 35535043 3 51 theme cytotoxicity 682:693 arg1 activity 702:709 antibody-dependent cellular cytotoxicity (ADCC) activity 654:709 antibody-dependent cellular cytotoxicity (ADCC) activity 654:709 Despite the consistency of purity, drifts in N-glycan profile were observed, which resulted in the variation of antibody-dependent cellular cytotoxicity (ADCC) activity. 35535043 2 52 theme China-sourced 415:427 arg1 pertuzumab 429:438 China-sourced pertuzumab 415:438 China-sourced pertuzumab (trademark: Perjeta®) 415:460 In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. 35535043 1 53 theme proposed 125:132 arg1 candidate 145:153 The proposed biosimilar candidate 121:153 The proposed biosimilar candidate 121:153 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35535043 1 54 theme target 231:236 arg1 profile 246:252 target product profile 231:252 target product profile 231:252 The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. 35762588 4 0 from moieties 685:692 arg1 cleavages 648:656 cleavages 648:656 cleavages at both glycan and peptide moieties 648:692 CID of magnesiated glycopeptide formed more cross-ring cleavages, whereas doubly sodiated species produced cleavages at both glycan and peptide moieties. 35762588 4 1 theme glycopeptide 560:571 arg1 CID 541:543 CID 541:543 CID of magnesiated glycopeptide 541:571 CID of magnesiated glycopeptide formed more cross-ring cleavages, whereas doubly sodiated species produced cleavages at both glycan and peptide moieties. 35762588 1 2 gly glycopeptide 337:348 arg2 glycopeptide 337:348 doubly charged glycopeptide 322:348 doubly charged glycopeptide 322:348 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 1 3 theme electron 175:182 arg1 ECD 206:208 ECD 206:208 ECD 206:208 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 1 3 theme electron 175:182 arg1 dissociation 192:203 electron capture dissociation 175:203 electron capture dissociation (ECD) 175:209 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 8 4 theme species 1152:1158 arg1 EED 1133:1135 EED 1133:1135 EED of magnesiated species 1133:1158 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 8 4 theme species 1152:1158 arg1 method 1201:1206 a one-step dissociation method 1177:1206 a one-step dissociation method for comprehensive structural analysis of glycopeptides 1177:1261 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 4 5 theme cross-ring 585:594 arg1 cleavages 596:604 more cross-ring cleavages 580:604 more cross-ring cleavages 580:604 CID of magnesiated glycopeptide formed more cross-ring cleavages, whereas doubly sodiated species produced cleavages at both glycan and peptide moieties. 35762588 5 6 theme charge 709:714 arg1 carriers 716:723 charge carriers 709:723 charge carriers 709:723 The effect of charge carriers on the fragmentation in ECD and EED was lower than that in CID. 35762588 1 7 theme capture 184:190 arg1 ECD 206:208 ECD 206:208 ECD 206:208 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 1 7 theme capture 184:190 arg1 dissociation 192:203 electron capture dissociation 175:203 electron capture dissociation (ECD) 175:209 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 4 8 theme more 580:583 arg1 cleavages 596:604 more cross-ring cleavages 580:604 more cross-ring cleavages 580:604 CID of magnesiated glycopeptide formed more cross-ring cleavages, whereas doubly sodiated species produced cleavages at both glycan and peptide moieties. 35762588 7 9 theme cross-ring 1048:1057 arg1 cleavages 1059:1067 more cross-ring cleavages 1043:1067 more cross-ring cleavages 1043:1067 Magnesiated species gave, however, more cross-ring cleavages than other charge carriers did. 35762588 6 10 theme glycan 865:870 arg1 moiety 872:877 the glycan moiety 861:877 the glycan moiety 861:877 ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. 35762588 2 11 theme mass 395:398 arg1 spectra 400:406 distinctively different tandem mass spectra 364:406 distinctively different tandem mass spectra for glycopeptide adducted with different charge carriers 364:463 CID produced distinctively different tandem mass spectra for glycopeptide adducted with different charge carriers. 35762588 4 12 gly glycopeptide 560:571 arg2 glycopeptide 560:571 magnesiated glycopeptide 548:571 magnesiated glycopeptide 548:571 CID of magnesiated glycopeptide formed more cross-ring cleavages, whereas doubly sodiated species produced cleavages at both glycan and peptide moieties. 35762588 4 13 theme glycan 666:671 arg1 moieties 685:692 both glycan and peptide moieties 661:692 moieties 685:692 CID of magnesiated glycopeptide formed more cross-ring cleavages, whereas doubly sodiated species produced cleavages at both glycan and peptide moieties. 35762588 2 14 theme different 378:386 arg1 spectra 400:406 distinctively different tandem mass spectra 364:406 distinctively different tandem mass spectra for glycopeptide adducted with different charge carriers 364:463 CID produced distinctively different tandem mass spectra for glycopeptide adducted with different charge carriers. 35762588 6 15 gly glycopeptide 895:906 arg2 glycopeptide 895:906 glycopeptide 895:906 glycopeptide 895:906 ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. 35762588 2 16 theme different 439:447 arg1 carriers 456:463 different charge carriers 439:463 different charge carriers 439:463 CID produced distinctively different tandem mass spectra for glycopeptide adducted with different charge carriers. 35762588 8 17 theme glycopeptides 1249:1261 arg1 analysis 1237:1244 comprehensive structural analysis 1212:1244 comprehensive structural analysis of glycopeptides 1212:1261 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 4 18 theme magnesiated 548:558 arg1 glycopeptide 560:571 magnesiated glycopeptide 548:571 magnesiated glycopeptide 548:571 CID of magnesiated glycopeptide formed more cross-ring cleavages, whereas doubly sodiated species produced cleavages at both glycan and peptide moieties. 35762588 7 19 theme Magnesiated 1008:1018 arg1 species 1020:1026 Magnesiated species 1008:1026 Magnesiated species 1008:1026 Magnesiated species gave, however, more cross-ring cleavages than other charge carriers did. 35762588 8 20 used used 1169:1172 arg2 method 1201:1206 a one-step dissociation method 1177:1206 a one-step dissociation method for comprehensive structural analysis of glycopeptides 1177:1261 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 8 20 used used 1169:1172 arg2 EED 1133:1135 EED 1133:1135 EED of magnesiated species 1133:1158 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 3 21 theme glycosidic 501:510 arg1 cleavages 512:520 mainly glycosidic cleavages 494:520 mainly glycosidic cleavages 494:520 Protonated species produced mainly glycosidic cleavages in high abundance. 35762588 0 22 theme Mass 7:10 arg1 Spectrometry 12:23 Tandem Mass Spectrometry 0:23 Tandem Mass Spectrometry for Structural Characterization of Doubly-Charged N-Linked Glycopeptides 0:96 Tandem Mass Spectrometry for Structural Characterization of Doubly-Charged N-Linked Glycopeptides. 35762588 8 23 theme comprehensive 1212:1224 arg1 analysis 1237:1244 comprehensive structural analysis 1212:1244 comprehensive structural analysis of glycopeptides 1212:1261 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 2 24 gly glycopeptide 412:423 arg2 glycopeptide 412:423 glycopeptide 412:423 glycopeptide adducted with different charge carriers 412:463 CID produced distinctively different tandem mass spectra for glycopeptide adducted with different charge carriers. 35762588 1 25 theme dissociation 105:116 arg1 methods 118:124 Three dissociation methods 99:124 Three dissociation methods 99:124 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 1 25 theme dissociation 105:116 arg1 dissociation 238:249 electronic excitation dissociation 216:249 electronic excitation dissociation (EED) 216:255 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 1 25 theme dissociation 105:116 arg1 dissociation 155:166 collision-induced dissociation 137:166 collision-induced dissociation (CID) 137:172 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 1 25 theme dissociation 105:116 arg1 dissociation 192:203 electron capture dissociation 175:203 electron capture dissociation (ECD) 175:209 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 6 26 theme molecular 959:967 arg1 ion 969:971 the molecular ion 955:971 the molecular ion regardless of the charge carriers 955:1005 ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. 35762588 0 27 theme Tandem 0:5 arg1 Spectrometry 12:23 Tandem Mass Spectrometry 0:23 Tandem Mass Spectrometry for Structural Characterization of Doubly-Charged N-Linked Glycopeptides 0:96 Tandem Mass Spectrometry for Structural Characterization of Doubly-Charged N-Linked Glycopeptides. 35762588 5 28 theme carriers 716:723 arg1 effect 699:704 The effect 695:704 The effect of charge carriers on the fragmentation in ECD and EED 695:759 The effect of charge carriers on the fragmentation in ECD and EED was lower than that in CID. 35762588 5 28 theme carriers 716:723 arg1 lower 765:769 lower 765:769 lower 765:769 The effect of charge carriers on the fragmentation in ECD and EED was lower than that in CID. 35762588 6 29 theme limited 840:846 arg1 cleavages 848:856 limited cleavages 840:856 limited cleavages at the glycan moiety 840:877 ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. 35762588 8 30 theme structural 1226:1235 arg1 analysis 1237:1244 comprehensive structural analysis 1212:1244 comprehensive structural analysis of glycopeptides 1212:1261 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 6 31 from moiety 872:877 arg1 cleavages 848:856 limited cleavages 840:856 limited cleavages at the glycan moiety 840:877 ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. 35762588 1 32 theme structural 291:300 arg1 characterization 302:317 structural characterization 291:317 structural characterization of doubly charged glycopeptide 291:348 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 3 33 theme high 525:528 arg1 abundance 530:538 high abundance 525:538 high abundance 525:538 Protonated species produced mainly glycosidic cleavages in high abundance. 35762588 5 34 from effect 699:704 arg1 fragmentation 732:744 the fragmentation 728:744 the fragmentation in ECD and EED 728:759 The effect of charge carriers on the fragmentation in ECD and EED was lower than that in CID. 35762588 7 35 theme other 1074:1078 arg1 carriers 1087:1094 other charge carriers 1074:1094 other charge carriers did 1074:1098 Magnesiated species gave, however, more cross-ring cleavages than other charge carriers did. 35762588 2 36 theme tandem 388:393 arg1 spectra 400:406 distinctively different tandem mass spectra 364:406 distinctively different tandem mass spectra for glycopeptide adducted with different charge carriers 364:463 CID produced distinctively different tandem mass spectra for glycopeptide adducted with different charge carriers. 35762588 6 37 theme extensive 920:928 arg1 fragmentation 930:942 extensive fragmentation 920:942 extensive fragmentation throughout the molecular ion regardless of the charge carriers 920:1005 ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. 35762588 1 38 theme electronic 216:225 arg1 EED 252:254 EED 252:254 EED 252:254 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 1 38 theme electronic 216:225 arg1 dissociation 238:249 electronic excitation dissociation 216:249 electronic excitation dissociation (EED) 216:255 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 0 39 theme Structural 29:38 arg1 Characterization 40:55 Structural Characterization 29:55 Structural Characterization of Doubly-Charged N-Linked Glycopeptides 29:96 Tandem Mass Spectrometry for Structural Characterization of Doubly-Charged N-Linked Glycopeptides. 35762588 5 40 from fragmentation 732:744 arg1 EED 757:759 EED 757:759 EED 757:759 The effect of charge carriers on the fragmentation in ECD and EED was lower than that in CID. 35762588 5 40 from fragmentation 732:744 arg1 ECD 749:751 ECD 749:751 ECD 749:751 The effect of charge carriers on the fragmentation in ECD and EED was lower than that in CID. 35762588 3 41 theme Protonated 466:475 arg1 species 477:483 Protonated species 466:483 Protonated species 466:483 Protonated species produced mainly glycosidic cleavages in high abundance. 35762588 1 42 theme excitation 227:236 arg1 EED 252:254 EED 252:254 EED 252:254 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 1 42 theme excitation 227:236 arg1 dissociation 238:249 electronic excitation dissociation 216:249 electronic excitation dissociation (EED) 216:255 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 0 43 theme Doubly-Charged 60:73 arg1 Glycopeptides 84:96 Doubly-Charged N-Linked Glycopeptides 60:96 Doubly-Charged N-Linked Glycopeptides 60:96 Tandem Mass Spectrometry for Structural Characterization of Doubly-Charged N-Linked Glycopeptides. 35762588 1 44 theme charged 329:335 arg1 glycopeptide 337:348 doubly charged glycopeptide 322:348 doubly charged glycopeptide 322:348 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 4 45 theme sodiated 622:629 arg1 species 631:637 doubly sodiated species 615:637 doubly sodiated species 615:637 CID of magnesiated glycopeptide formed more cross-ring cleavages, whereas doubly sodiated species produced cleavages at both glycan and peptide moieties. 35762588 6 46 theme backbone 817:824 arg1 cleavages 826:834 peptide backbone cleavages 809:834 peptide backbone cleavages 809:834 ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. 35762588 1 47 theme collision-induced 137:153 arg1 CID 169:171 CID 169:171 CID 169:171 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 1 47 theme collision-induced 137:153 arg1 dissociation 155:166 collision-induced dissociation 137:166 collision-induced dissociation (CID) 137:172 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 1 48 theme glycopeptide 337:348 arg1 characterization 302:317 structural characterization 291:317 structural characterization of doubly charged glycopeptide 291:348 Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. 35762588 6 49 theme glycopeptide 895:906 arg1 EED 888:890 EED 888:890 EED of glycopeptide 888:906 ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. 35762588 6 50 theme peptide 809:815 arg1 cleavages 826:834 peptide backbone cleavages 809:834 peptide backbone cleavages 809:834 ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. 35762588 8 51 theme dissociation 1188:1199 arg1 EED 1133:1135 EED 1133:1135 EED of magnesiated species 1133:1158 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 8 51 theme dissociation 1188:1199 arg1 method 1201:1206 a one-step dissociation method 1177:1206 a one-step dissociation method for comprehensive structural analysis of glycopeptides 1177:1261 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 7 52 theme charge 1080:1085 arg1 carriers 1087:1094 other charge carriers 1074:1094 other charge carriers did 1074:1098 Magnesiated species gave, however, more cross-ring cleavages than other charge carriers did. 35762588 8 53 theme one-step 1179:1186 arg1 EED 1133:1135 EED 1133:1135 EED of magnesiated species 1133:1158 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 8 53 theme one-step 1179:1186 arg1 method 1201:1206 a one-step dissociation method 1177:1206 a one-step dissociation method for comprehensive structural analysis of glycopeptides 1177:1261 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 4 54 theme peptide 677:683 arg1 moieties 685:692 both glycan and peptide moieties 661:692 moieties 685:692 CID of magnesiated glycopeptide formed more cross-ring cleavages, whereas doubly sodiated species produced cleavages at both glycan and peptide moieties. 35762588 0 55 theme Glycopeptides 84:96 arg1 Characterization 40:55 Structural Characterization 29:55 Structural Characterization of Doubly-Charged N-Linked Glycopeptides 29:96 Tandem Mass Spectrometry for Structural Characterization of Doubly-Charged N-Linked Glycopeptides. 35762588 2 56 theme charge 449:454 arg1 carriers 456:463 different charge carriers 439:463 different charge carriers 439:463 CID produced distinctively different tandem mass spectra for glycopeptide adducted with different charge carriers. 35762588 0 57 theme N-Linked 75:82 arg1 Glycopeptides 84:96 Doubly-Charged N-Linked Glycopeptides 60:96 Doubly-Charged N-Linked Glycopeptides 60:96 Tandem Mass Spectrometry for Structural Characterization of Doubly-Charged N-Linked Glycopeptides. 35762588 6 58 theme charge 991:996 arg1 carriers 998:1005 the charge carriers 987:1005 the charge carriers 987:1005 ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. 35762588 8 59 theme magnesiated 1140:1150 arg1 species 1152:1158 magnesiated species 1140:1158 magnesiated species 1140:1158 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 35762588 8 60 gly glycopeptides 1249:1261 arg2 glycopeptides 1249:1261 glycopeptides 1249:1261 glycopeptides 1249:1261 These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides. 36412635 2 0 theme disease 345:351 arg1 biomarkers 315:324 biomarkers 315:324 biomarkers of risk and occult disease 315:351 Proteomics analysis of breast milk may provide biomarkers of risk and occult disease. 36412635 4 1 from donors 627:632 arg1 samples 614:620 12 milk samples 606:620 12 milk samples from donors with BC and matched controls 606:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 4 1 from donors 627:632 arg1 analysis 594:601 mass spectrometry (MS)-based proteomics analysis 554:601 mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls 554:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 5 2 theme 1D 703:704 arg1 PAGE 743:746 PAGE 743:746 PAGE 743:746 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 5 2 theme 1D 703:704 arg1 electrophoresis 726:740 one-dimensional (1D)-polyacrylamide gel electrophoresis 686:740 one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS) 686:811 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 1 3 theme accurate 159:166 arg1 assessment 173:182 accurate risk assessment 159:182 accurate risk assessment 159:182 It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. 36412635 4 4 theme current 531:537 arg1 study 539:543 the current study 527:543 the current study 527:543 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 7 5 theme histone-lysine 1205:1218 arg1 methyltransferase 1220:1236 histone-lysine methyltransferase 1205:1236 histone-lysine methyltransferase 1205:1236 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 5 theme histone-lysine 1205:1218 arg1 A 1094:1094 Lactadherin isoform A 1074:1094 Lactadherin isoform A 1074:1094 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 2 6 theme occult 338:343 arg1 disease 345:351 occult disease 338:351 occult disease 338:351 Proteomics analysis of breast milk may provide biomarkers of risk and occult disease. 36412635 8 7 theme current 1287:1293 arg1 understanding 1295:1307 our current understanding 1283:1307 our current understanding of using milk 1283:1321 Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. 36412635 8 7 theme current 1287:1293 arg1 fluid 1339:1343 a biological fluid 1326:1343 a biological fluid for identification of BC-related dysregulated proteins 1326:1398 Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. 36412635 9 8 theme risk 1523:1526 arg1 assessment 1528:1537 risk assessment 1523:1537 risk assessment 1523:1537 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 1 9 theme cancer-related 242:255 arg1 mortality 257:265 cancer-related mortality 242:265 cancer-related mortality 242:265 It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. 36412635 9 10 theme early 1503:1507 arg1 detection 1509:1517 early detection 1503:1517 early detection 1503:1517 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 7 11 theme cancer 1046:1051 arg1 development 1053:1063 cancer development 1046:1063 cancer development 1046:1063 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 12 theme Lactadherin 1074:1084 arg1 transferase 1135:1145 O-linked N-acetylglucosamine (GlcNAc) transferase 1097:1145 O-linked N-acetylglucosamine (GlcNAc) transferase 1097:1145 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 12 theme Lactadherin 1074:1084 arg1 A 1094:1094 Lactadherin isoform A 1074:1094 Lactadherin isoform A 1074:1094 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 12 theme Lactadherin 1074:1084 arg1 isoform 1194:1200 perilipin-3 isoform 1 1182:1202 perilipin-3 isoform 1 1182:1202 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 12 theme Lactadherin 1074:1084 arg1 galactosyltransferase 1148:1168 galactosyltransferase 1148:1168 galactosyltransferase 1148:1168 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 12 theme Lactadherin 1074:1084 arg1 chain 1257:1261 clathrin heavy chain 1242:1261 clathrin heavy chain 1242:1261 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 12 theme Lactadherin 1074:1084 arg1 recoverin 1171:1179 recoverin 1171:1179 recoverin 1171:1179 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 12 theme Lactadherin 1074:1084 arg1 methyltransferase 1220:1236 histone-lysine methyltransferase 1205:1236 histone-lysine methyltransferase 1205:1236 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 9 13 theme biomarker 1482:1490 arg1 discovery 1492:1500 BC biomarker discovery 1479:1500 BC biomarker discovery 1479:1500 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 7 14 from dysregulations 990:1003 arg1 proteins 1013:1020 milk proteins 1008:1020 milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain 1008:1261 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 6 15 theme milk 946:949 arg1 samples 951:957 milk samples 946:957 milk samples 946:957 We confirmed the dysregulation of several proteins identified previously in a different set of milk samples. 36412635 4 16 with donors 627:632 arg1 BC 639:640 BC 639:640 BC 639:640 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 4 16 with donors 627:632 arg1 controls 654:661 matched controls 646:661 matched controls 646:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 5 17 theme nanoliquid 762:771 arg1 nanoLC-MS/MS 799:810 nanoLC-MS/MS 799:810 nanoLC-MS/MS 799:810 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 5 17 theme nanoliquid 762:771 arg1 MS 795:796 nanoliquid chromatography tandem MS 762:796 nanoliquid chromatography tandem MS (nanoLC-MS/MS) 762:811 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 2 18 theme Proteomics 268:277 arg1 analysis 279:286 Proteomics analysis 268:286 Proteomics analysis of breast milk 268:301 Proteomics analysis of breast milk may provide biomarkers of risk and occult disease. 36412635 4 19 theme milk 609:612 arg1 samples 614:620 12 milk samples 606:620 12 milk samples from donors with BC and matched controls 606:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 1 20 theme risk 168:171 arg1 assessment 173:182 accurate risk assessment 159:182 accurate risk assessment 159:182 It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. 36412635 0 21 theme Breast 109:114 arg1 Cancer 116:121 Breast Cancer 109:121 Breast Cancer 109:121 Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls. 36412635 5 22 theme bioinformatics 826:839 arg1 analysis 841:848 bioinformatics analysis 826:848 bioinformatics analysis 826:848 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 3 23 theme human 389:393 arg1 samples 400:406 human milk samples 389:406 human milk samples from women with BC and controls 389:438 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 9 24 dep young 1542:1546 arg1 active 1564:1569 active 1564:1569 active 1564:1569 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 7 25 theme N-acetylglucosamine 1106:1124 arg1 transferase 1135:1145 O-linked N-acetylglucosamine (GlcNAc) transferase 1097:1145 O-linked N-acetylglucosamine (GlcNAc) transferase 1097:1145 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 25 theme N-acetylglucosamine 1106:1124 arg1 A 1094:1094 Lactadherin isoform A 1074:1094 Lactadherin isoform A 1074:1094 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 0 26 theme Spectrometry-Based 5:22 arg1 Proteomics 24:33 Mass Spectrometry-Based Proteomics 0:33 Mass Spectrometry-Based Proteomics of Human Milk 0:47 Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls. 36412635 6 27 theme proteins 893:900 arg1 dysregulation 868:880 the dysregulation 864:880 the dysregulation of several proteins identified previously in a different set of milk samples 864:957 We confirmed the dysregulation of several proteins identified previously in a different set of milk samples. 36412635 3 28 from alterations 455:465 arg1 patterns 478:485 protein patterns 470:485 protein patterns of milk 470:493 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 8 29 theme milk 1318:1321 arg1 understanding 1295:1307 our current understanding 1283:1307 our current understanding of using milk 1283:1321 Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. 36412635 8 29 theme milk 1318:1321 arg1 fluid 1339:1343 a biological fluid 1326:1343 a biological fluid for identification of BC-related dysregulated proteins 1326:1398 Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. 36412635 4 30 from analysis 594:601 arg1 donors 627:632 donors 627:632 donors with BC and matched controls 627:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 3 31 theme samples 400:406 arg1 analysis 377:384 the analysis 373:384 the analysis of human milk samples from women with BC and controls 373:438 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 0 32 theme Mass 0:3 arg1 Proteomics 24:33 Mass Spectrometry-Based Proteomics 0:33 Mass Spectrometry-Based Proteomics of Human Milk 0:47 Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls. 36412635 7 33 theme isoform 1086:1092 arg1 transferase 1135:1145 O-linked N-acetylglucosamine (GlcNAc) transferase 1097:1145 O-linked N-acetylglucosamine (GlcNAc) transferase 1097:1145 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 33 theme isoform 1086:1092 arg1 A 1094:1094 Lactadherin isoform A 1074:1094 Lactadherin isoform A 1074:1094 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 33 theme isoform 1086:1092 arg1 isoform 1194:1200 perilipin-3 isoform 1 1182:1202 perilipin-3 isoform 1 1182:1202 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 33 theme isoform 1086:1092 arg1 galactosyltransferase 1148:1168 galactosyltransferase 1148:1168 galactosyltransferase 1148:1168 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 33 theme isoform 1086:1092 arg1 chain 1257:1261 clathrin heavy chain 1242:1261 clathrin heavy chain 1242:1261 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 33 theme isoform 1086:1092 arg1 recoverin 1171:1179 recoverin 1171:1179 recoverin 1171:1179 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 33 theme isoform 1086:1092 arg1 methyltransferase 1220:1236 histone-lysine methyltransferase 1205:1236 histone-lysine methyltransferase 1205:1236 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 5 34 used used 681:684 arg2 we 678:679 we 678:679 we 678:679 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 8 35 theme using 1312:1316 arg1 milk 1318:1321 using milk 1312:1321 using milk 1312:1321 Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. 36412635 1 36 theme early 188:192 arg1 diagnosis 194:202 early diagnosis 188:202 early diagnosis 188:202 It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. 36412635 5 37 theme chromatography 773:786 arg1 nanoLC-MS/MS 799:810 nanoLC-MS/MS 799:810 nanoLC-MS/MS 799:810 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 5 37 theme chromatography 773:786 arg1 MS 795:796 nanoliquid chromatography tandem MS 762:796 nanoliquid chromatography tandem MS (nanoLC-MS/MS) 762:811 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 8 38 theme proteins 1391:1398 arg1 identification 1349:1362 identification 1349:1362 identification of BC-related dysregulated proteins 1349:1398 Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. 36412635 0 39 with Women 98:102 arg1 Controls 130:137 Controls 130:137 Controls 130:137 Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls. 36412635 0 39 with Women 98:102 arg1 Cancer 116:121 Breast Cancer 109:121 Breast Cancer 109:121 Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls. 36412635 2 40 theme milk 298:301 arg1 analysis 279:286 Proteomics analysis 268:286 Proteomics analysis of breast milk 268:301 Proteomics analysis of breast milk may provide biomarkers of risk and occult disease. 36412635 7 41 theme heavy 1251:1255 arg1 chain 1257:1261 clathrin heavy chain 1242:1261 clathrin heavy chain 1242:1261 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 41 theme heavy 1251:1255 arg1 A 1094:1094 Lactadherin isoform A 1074:1094 Lactadherin isoform A 1074:1094 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 42 theme clathrin 1242:1249 arg1 chain 1257:1261 clathrin heavy chain 1242:1261 clathrin heavy chain 1242:1261 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 42 theme clathrin 1242:1249 arg1 A 1094:1094 Lactadherin isoform A 1074:1094 Lactadherin isoform A 1074:1094 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 2 43 theme breast 291:296 arg1 milk 298:301 breast milk 291:301 breast milk 291:301 Proteomics analysis of breast milk may provide biomarkers of risk and occult disease. 36412635 9 44 from assessment 1528:1537 arg1 women 1571:1575 young, reproductively active women 1542:1575 young, reproductively active women 1542:1575 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 4 45 theme MS 573:574 arg1 analysis 594:601 mass spectrometry (MS)-based proteomics analysis 554:601 mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls 554:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 0 46 theme Milk 44:47 arg1 Proteomics 24:33 Mass Spectrometry-Based Proteomics 0:33 Mass Spectrometry-Based Proteomics of Human Milk 0:47 Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls. 36412635 3 47 theme protein 470:476 arg1 patterns 478:485 protein patterns 470:485 protein patterns of milk 470:493 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 4 48 used used 549:552 arg2 we 546:547 we 546:547 we 546:547 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 4 49 theme proteomics 583:592 arg1 analysis 594:601 mass spectrometry (MS)-based proteomics analysis 554:601 mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls 554:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 1 50 theme breast 207:212 arg1 BC 222:223 BC 222:223 BC 222:223 It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. 36412635 1 50 theme breast 207:212 arg1 cancer 214:219 breast cancer 207:219 breast cancer (BC) 207:224 It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. 36412635 0 51 theme Human 38:42 arg1 Milk 44:47 Human Milk 38:47 Human Milk 38:47 Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls. 36412635 6 52 theme several 885:891 arg1 proteins 893:900 several proteins 885:900 several proteins identified previously in a different set of milk samples 885:957 We confirmed the dysregulation of several proteins identified previously in a different set of milk samples. 36412635 3 53 theme milk 395:398 arg1 samples 400:406 human milk samples 389:406 human milk samples from women with BC and controls 389:438 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 8 54 theme biological 1328:1337 arg1 understanding 1295:1307 our current understanding 1283:1307 our current understanding of using milk 1283:1321 Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. 36412635 8 54 theme biological 1328:1337 arg1 fluid 1339:1343 a biological fluid 1326:1343 a biological fluid for identification of BC-related dysregulated proteins 1326:1398 Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. 36412635 5 55 theme tandem 788:793 arg1 nanoLC-MS/MS 799:810 nanoLC-MS/MS 799:810 nanoLC-MS/MS 799:810 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 5 55 theme tandem 788:793 arg1 MS 795:796 nanoliquid chromatography tandem MS 762:796 nanoliquid chromatography tandem MS (nanoLC-MS/MS) 762:811 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 1 56 theme cancer 214:219 arg1 assessment 173:182 accurate risk assessment 159:182 accurate risk assessment 159:182 It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. 36412635 1 56 theme cancer 214:219 arg1 diagnosis 194:202 early diagnosis 188:202 early diagnosis 188:202 It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. 36412635 5 57 theme gel 722:724 arg1 PAGE 743:746 PAGE 743:746 PAGE 743:746 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 5 57 theme gel 722:724 arg1 electrophoresis 726:740 one-dimensional (1D)-polyacrylamide gel electrophoresis 686:740 one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS) 686:811 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 7 58 theme additional 979:988 arg1 dysregulations 990:1003 additional dysregulations 979:1003 additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain 979:1261 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 9 59 theme young 1542:1546 arg1 women 1571:1575 young, reproductively active women 1542:1575 young, reproductively active women 1542:1575 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 7 60 theme milk 1008:1011 arg1 proteins 1013:1020 milk proteins 1008:1020 milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain 1008:1261 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 9 61 contain has 1446:1448 arg1 milk 1441:1444 milk 1441:1444 milk 1441:1444 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 9 61 contain has 1446:1448 arg2 potential 1454:1462 the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women 1450:1575 the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women 1450:1575 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 7 62 theme perilipin-3 1182:1192 arg1 isoform 1194:1200 perilipin-3 isoform 1 1182:1202 perilipin-3 isoform 1 1182:1202 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 62 theme perilipin-3 1182:1192 arg1 A 1094:1094 Lactadherin isoform A 1074:1094 Lactadherin isoform A 1074:1094 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 6 63 theme different 929:937 arg1 set 939:941 a different set 927:941 a different set of milk samples 927:957 We confirmed the dysregulation of several proteins identified previously in a different set of milk samples. 36412635 6 63 theme different 929:937 arg1 samples 951:957 milk samples 946:957 milk samples 946:957 We confirmed the dysregulation of several proteins identified previously in a different set of milk samples. 36412635 2 64 theme risk 329:332 arg1 biomarkers 315:324 biomarkers 315:324 biomarkers of risk and occult disease 315:351 Proteomics analysis of breast milk may provide biomarkers of risk and occult disease. 36412635 8 65 theme dysregulated 1378:1389 arg1 proteins 1391:1398 BC-related dysregulated proteins 1367:1398 BC-related dysregulated proteins 1367:1398 Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. 36412635 3 66 with women 413:417 arg1 controls 431:438 controls 431:438 controls 431:438 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 3 66 with women 413:417 arg1 BC 424:425 BC 424:425 BC 424:425 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 8 67 theme BC-related 1367:1376 arg1 proteins 1391:1398 BC-related dysregulated proteins 1367:1398 BC-related dysregulated proteins 1367:1398 Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. 36412635 4 68 theme mass 554:557 arg1 analysis 594:601 mass spectrometry (MS)-based proteomics analysis 554:601 mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls 554:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 9 69 theme BC 1479:1480 arg1 discovery 1492:1500 BC biomarker discovery 1479:1500 BC biomarker discovery 1479:1500 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 7 70 theme O-linked 1097:1104 arg1 GlcNAc 1127:1132 GlcNAc 1127:1132 GlcNAc 1127:1132 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 70 theme O-linked 1097:1104 arg1 N-acetylglucosamine 1106:1124 O-linked N-acetylglucosamine 1097:1124 O-linked N-acetylglucosamine (GlcNAc) transferase 1097:1145 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 4 71 theme matched 646:652 arg1 controls 654:661 matched controls 646:661 matched controls 646:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 0 72 theme Expressed 76:84 arg1 Proteins 86:93 Differentially Expressed Proteins 61:93 Differentially Expressed Proteins 61:93 Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls. 36412635 4 73 theme -based 576:581 arg1 analysis 594:601 mass spectrometry (MS)-based proteomics analysis 554:601 mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls 554:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 7 74 link O-linked 1097:1104 arg1 GlcNAc 1127:1132 GlcNAc 1127:1132 GlcNAc 1127:1132 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 7 74 link O-linked 1097:1104 arg1 N-acetylglucosamine 1106:1124 O-linked N-acetylglucosamine 1097:1124 O-linked N-acetylglucosamine (GlcNAc) transferase 1097:1145 We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. 36412635 3 75 theme milk 490:493 arg1 patterns 478:485 protein patterns 470:485 protein patterns of milk 470:493 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 9 76 from detection 1509:1517 arg1 women 1571:1575 young, reproductively active women 1542:1575 young, reproductively active women 1542:1575 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 6 77 theme samples 951:957 arg1 set 939:941 a different set 927:941 a different set of milk samples 927:957 We confirmed the dysregulation of several proteins identified previously in a different set of milk samples. 36412635 6 77 theme samples 951:957 arg1 samples 951:957 milk samples 946:957 milk samples 946:957 We confirmed the dysregulation of several proteins identified previously in a different set of milk samples. 36412635 5 78 theme one-dimensional 686:700 arg1 PAGE 743:746 PAGE 743:746 PAGE 743:746 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 5 78 theme one-dimensional 686:700 arg1 electrophoresis 726:740 one-dimensional (1D)-polyacrylamide gel electrophoresis 686:740 one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS) 686:811 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 3 79 from analysis 377:384 arg1 women 413:417 women 413:417 women with BC and controls 413:438 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 5 80 theme -polyacrylamide 706:720 arg1 PAGE 743:746 PAGE 743:746 PAGE 743:746 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 5 80 theme -polyacrylamide 706:720 arg1 electrophoresis 726:740 one-dimensional (1D)-polyacrylamide gel electrophoresis 686:740 one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS) 686:811 Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. 36412635 3 81 from women 413:417 arg1 samples 400:406 human milk samples 389:406 human milk samples from women with BC and controls 389:438 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 3 81 from women 413:417 arg1 analysis 377:384 the analysis 373:384 the analysis of human milk samples from women with BC and controls 373:438 Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. 36412635 4 82 theme samples 614:620 arg1 analysis 594:601 mass spectrometry (MS)-based proteomics analysis 554:601 mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls 554:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36412635 9 83 from discovery 1492:1500 arg1 women 1571:1575 young, reproductively active women 1542:1575 young, reproductively active women 1542:1575 Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. 36412635 4 84 theme spectrometry 559:570 arg1 analysis 594:601 mass spectrometry (MS)-based proteomics analysis 554:601 mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls 554:661 In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. 36377513 10 0 dep CONCLUSIONS 1552:1562 arg1 investigation 1606:1618 the first functional investigation 1585:1618 the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1585:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 10 0 dep CONCLUSIONS 1552:1562 arg1 study 1576:1580 The present study 1564:1580 The present study 1564:1580 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 4 1 dep METHOD 534:539 arg1 microarray 562:571 A lectin microarray 553:571 A lectin microarray 553:571 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 10 2 theme therapeutic 1782:1792 arg1 targets 1794:1800 identified potential therapeutic targets 1761:1800 identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1761:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 1 3 theme scar 255:258 arg1 formation 260:268 glial scar formation 249:268 glial scar formation upon spinal cord injury (SCI) 249:298 INTRODUCTION Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. 36377513 2 4 from phases 448:453 arg1 inflammation 391:402 inflammation 391:402 inflammation 391:402 Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodeling from acute to chronic phases. 36377513 2 4 from phases 448:453 arg1 remodeling 415:424 tissue remodeling 408:424 tissue remodeling 408:424 Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodeling from acute to chronic phases. 36377513 0 5 theme inflammation 162:173 arg1 phases 152:157 the chronic phases 140:157 the chronic phases of inflammation 140:173 An insight into new glycotherapeutics in glial inflammation: Understanding the role of glycosylation in mitochondrial function and acute to the chronic phases of inflammation. 36377513 3 6 theme glial 508:512 arg1 cells 514:518 these glial cells 502:518 these glial cells 502:518 Therefore, understating the glycan changes in these glial cells is paramount. 36377513 0 7 theme glycosylation 87:99 arg1 role 79:82 the role 75:82 the role of glycosylation in mitochondrial function 75:125 An insight into new glycotherapeutics in glial inflammation: Understanding the role of glycosylation in mitochondrial function and acute to the chronic phases of inflammation. 36377513 10 8 theme potential 1772:1780 arg1 targets 1794:1800 identified potential therapeutic targets 1761:1800 identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1761:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 7 9 dep Control 1148:1154 arg1 treatments 1164:1173 treatments 1164:1173 treatments 1164:1173 Control and LPS treatments were observed to be in dense clusters. 36377513 10 10 theme modulation 1637:1646 arg1 investigation 1606:1618 the first functional investigation 1585:1618 the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1585:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 10 10 theme modulation 1637:1646 arg1 study 1576:1580 The present study 1564:1580 The present study 1564:1580 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 6 11 theme LPS 1087:1089 arg1 groups 1099:1104 the control, cytokine combination, and LPS treated groups 1048:1104 the control, cytokine combination, and LPS treated groups 1048:1104 Pearson's correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. 36377513 10 12 theme glycosylation 1623:1635 arg1 modulation 1637:1646 glycosylation modulation 1623:1646 glycosylation modulation 1623:1646 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 6 13 theme hierarchical 929:940 arg1 clustering 942:951 Pearson's correlation hierarchical clustering 907:951 Pearson's correlation hierarchical clustering 907:951 Pearson's correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. 36377513 1 14 theme spinal 275:280 arg1 SCI 295:297 SCI 295:297 SCI 295:297 INTRODUCTION Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. 36377513 1 14 theme spinal 275:280 arg1 injury 287:292 spinal cord injury 275:292 spinal cord injury (SCI) 275:298 INTRODUCTION Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. 36377513 0 15 theme mitochondrial 104:116 arg1 function 118:125 mitochondrial function 104:125 mitochondrial function 104:125 An insight into new glycotherapeutics in glial inflammation: Understanding the role of glycosylation in mitochondrial function and acute to the chronic phases of inflammation. 36377513 6 16 theme correlation 917:927 arg1 clustering 942:951 Pearson's correlation hierarchical clustering 907:951 Pearson's correlation hierarchical clustering 907:951 Pearson's correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. 36377513 6 17 theme treated 1091:1097 arg1 groups 1099:1104 the control, cytokine combination, and LPS treated groups 1048:1104 the control, cytokine combination, and LPS treated groups 1048:1104 Pearson's correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. 36377513 10 18 theme glyco 1813:1817 arg1 therapeutics 1819:1830 future glyco therapeutics 1806:1830 future glyco therapeutics in neuroinflammation 1806:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 9 19 theme expression 1487:1496 arg1 upregulation 1455:1466 upregulation 1455:1466 upregulation of the sialic acid expression 1455:1496 However, the sialyltransferase inhibitor inhibited this modification (upregulation of the sialic acid expression), which indeed modulates the mitochondrial functions. 36377513 4 20 theme differential 675:686 arg1 glycosylation 688:700 considerable differential glycosylation 662:700 considerable differential glycosylation 662:700 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 8 21 theme lectin 1246:1251 arg1 immunostaining 1253:1266 lectin immunostaining 1246:1266 lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia 1246:1382 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 10 22 theme culture 1665:1671 arg1 model 1673:1677 a mixed glial culture model 1651:1677 a mixed glial culture model 1651:1677 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 2 23 dep acute 431:435 arg1 chronic 440:446 chronic 440:446 chronic 440:446 Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodeling from acute to chronic phases. 36377513 2 23 dep acute 431:435 arg1 to 437:438 to 437:438 to 437:438 Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodeling from acute to chronic phases. 36377513 6 24 theme combination 1070:1080 arg1 groups 1099:1104 the control, cytokine combination, and LPS treated groups 1048:1104 the control, cytokine combination, and LPS treated groups 1048:1104 Pearson's correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. 36377513 4 25 theme considerable 662:673 arg1 glycosylation 688:700 considerable differential glycosylation 662:700 considerable differential glycosylation 662:700 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 7 26 theme dense 1198:1202 arg1 clusters 1204:1211 dense clusters 1198:1211 dense clusters 1198:1211 Control and LPS treatments were observed to be in dense clusters. 36377513 0 27 from glycotherapeutics 20:36 arg1 inflammation 47:58 glial inflammation 41:58 glial inflammation 41:58 An insight into new glycotherapeutics in glial inflammation: Understanding the role of glycosylation in mitochondrial function and acute to the chronic phases of inflammation. 36377513 10 28 theme mixed 1653:1657 arg1 model 1673:1677 a mixed glial culture model 1651:1677 a mixed glial culture model 1651:1677 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 4 29 theme generated 764:772 arg1 model 787:791 a cytokine-combination generated inflamed MGC model 741:791 a cytokine-combination generated inflamed MGC model 741:791 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 1 30 theme INTRODUCTION 176:187 arg1 Glycosylation 189:201 INTRODUCTION Glycosylation 176:201 INTRODUCTION Glycosylation 176:201 INTRODUCTION Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. 36377513 5 31 theme O-linked 827:834 arg1 glycans 836:842 several N- and O-linked glycans 812:842 glycans 836:842 It was found that several N- and O-linked glycans associated with glia during SCI were differentially regulated. 36377513 1 32 theme cord 282:285 arg1 SCI 295:297 SCI 295:297 SCI 295:297 INTRODUCTION Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. 36377513 1 32 theme cord 282:285 arg1 injury 287:292 spinal cord injury 275:292 spinal cord injury (SCI) 275:298 INTRODUCTION Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. 36377513 3 33 from changes 491:497 arg1 cells 514:518 these glial cells 502:518 these glial cells 502:518 Therefore, understating the glycan changes in these glial cells is paramount. 36377513 6 34 theme control 1052:1058 arg1 groups 1099:1104 the control, cytokine combination, and LPS treated groups 1048:1104 the control, cytokine combination, and LPS treated groups 1048:1104 Pearson's correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. 36377513 9 35 dep modification 1441:1452 arg1 upregulation 1455:1466 upregulation 1455:1466 upregulation of the sialic acid expression 1455:1496 However, the sialyltransferase inhibitor inhibited this modification (upregulation of the sialic acid expression), which indeed modulates the mitochondrial functions. 36377513 0 36 theme new 16:18 arg1 glycotherapeutics 20:36 new glycotherapeutics 16:36 new glycotherapeutics in glial inflammation 16:58 An insight into new glycotherapeutics in glial inflammation: Understanding the role of glycosylation in mitochondrial function and acute to the chronic phases of inflammation. 36377513 4 37 theme MGC 783:785 arg1 model 787:791 a cytokine-combination generated inflamed MGC model 741:791 a cytokine-combination generated inflamed MGC model 741:791 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 2 38 theme acute 431:435 arg1 phases 448:453 acute to chronic phases 431:453 acute to chronic phases 431:453 Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodeling from acute to chronic phases. 36377513 0 39 from role 79:82 arg1 function 118:125 mitochondrial function 104:125 mitochondrial function 104:125 An insight into new glycotherapeutics in glial inflammation: Understanding the role of glycosylation in mitochondrial function and acute to the chronic phases of inflammation. 36377513 4 40 theme inflamed 774:781 arg1 model 787:791 a cytokine-combination generated inflamed MGC model 741:791 a cytokine-combination generated inflamed MGC model 741:791 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 4 41 theme culture 637:643 arg1 model 645:649 a cytokine-driven inflammatory mixed glial culture model 594:649 a cytokine-driven inflammatory mixed glial culture model 594:649 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 4 42 theme lectin 555:560 arg1 microarray 562:571 A lectin microarray 553:571 A lectin microarray 553:571 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 1 43 theme critical 211:218 arg1 role 220:223 a critical role 209:223 a critical role 209:223 INTRODUCTION Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. 36377513 10 44 from therapeutics 1819:1830 arg1 neuroinflammation 1835:1851 neuroinflammation 1835:1851 neuroinflammation 1835:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 2 45 theme tissue 408:413 arg1 remodeling 415:424 tissue remodeling 408:424 tissue remodeling 408:424 Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodeling from acute to chronic phases. 36377513 9 46 theme sialic 1475:1480 arg1 acid 1482:1485 the sialic acid 1471:1485 the sialic acid expression 1471:1496 However, the sialyltransferase inhibitor inhibited this modification (upregulation of the sialic acid expression), which indeed modulates the mitochondrial functions. 36377513 6 47 theme several 992:998 arg1 clusters 1000:1007 several clusters 992:1007 several clusters 992:1007 Pearson's correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. 36377513 9 48 theme sialyltransferase 1398:1414 arg1 inhibitor 1416:1424 the sialyltransferase inhibitor 1394:1424 the sialyltransferase inhibitor 1394:1424 However, the sialyltransferase inhibitor inhibited this modification (upregulation of the sialic acid expression), which indeed modulates the mitochondrial functions. 36377513 6 49 theme cytokine 1061:1068 arg1 combination 1070:1080 cytokine combination 1061:1080 cytokine combination 1061:1080 Pearson's correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. 36377513 8 50 theme sialic 1313:1318 arg1 residues 1333:1340 sialic acid-binding residues 1313:1340 sialic acid-binding residues 1313:1340 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 5 51 theme several 812:818 arg1 N- 820:821 several N- and O-linked glycans 812:842 N- 820:821 It was found that several N- and O-linked glycans associated with glia during SCI were differentially regulated. 36377513 1 52 theme disease 300:306 arg1 progression 308:318 disease progression 300:318 disease progression 300:318 INTRODUCTION Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. 36377513 0 53 theme chronic 144:150 arg1 phases 152:157 the chronic phases 140:157 the chronic phases of inflammation 140:173 An insight into new glycotherapeutics in glial inflammation: Understanding the role of glycosylation in mitochondrial function and acute to the chronic phases of inflammation. 36377513 1 54 dep inflammation 232:243 arg1 progression 308:318 disease progression 300:318 disease progression 300:318 INTRODUCTION Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. 36377513 9 55 dep inhibited 1426:1434 arg1 modulates 1513:1521 modulates 1513:1521 modulates the mitochondrial functions 1513:1549 However, the sialyltransferase inhibitor inhibited this modification (upregulation of the sialic acid expression), which indeed modulates the mitochondrial functions. 36377513 10 56 theme identified 1761:1770 arg1 targets 1794:1800 identified potential therapeutic targets 1761:1800 identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1761:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 0 57 theme glial 41:45 arg1 inflammation 47:58 glial inflammation 41:58 glial inflammation 41:58 An insight into new glycotherapeutics in glial inflammation: Understanding the role of glycosylation in mitochondrial function and acute to the chronic phases of inflammation. 36377513 10 58 theme present 1568:1574 arg1 investigation 1606:1618 the first functional investigation 1585:1618 the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1585:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 10 58 theme present 1568:1574 arg1 study 1576:1580 The present study 1564:1580 The present study 1564:1580 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 10 59 theme glycome 1713:1719 arg1 role 1701:1704 the role 1697:1704 the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1697:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 4 60 theme chronic 724:730 arg1 phase 732:736 the chronic phase 720:736 the chronic phase in a cytokine-combination generated inflamed MGC model 720:791 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 5 61 link O-linked 827:834 arg1 glycans 836:842 several N- and O-linked glycans 812:842 glycans 836:842 It was found that several N- and O-linked glycans associated with glia during SCI were differentially regulated. 36377513 8 62 located detected 1347:1354 arg2 fucose 1302:1307 fucose 1302:1307 fucose 1302:1307 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 8 62 located detected 1347:1354 arg2 GlcNAc 1285:1290 GlcNAc 1285:1290 GlcNAc 1285:1290 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 8 62 located detected 1347:1354 arg2 mannose 1293:1299 mannose 1293:1299 mannose 1293:1299 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 8 62 located detected 1347:1354 arg2 residues 1333:1340 sialic acid-binding residues 1313:1340 sialic acid-binding residues 1313:1340 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 8 62 located detected 1347:1354 arg1 astrocytes 1359:1368 astrocytes 1359:1368 astrocytes 1359:1368 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 8 62 located detected 1347:1354 arg1 immunostaining 1253:1266 lectin immunostaining 1246:1266 lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia 1246:1382 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 8 62 located detected 1347:1354 arg1 microglia 1374:1382 microglia 1374:1382 microglia 1374:1382 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 8 62 located detected 1347:1354 arg2 GalNAc 1277:1282 GalNAc 1277:1282 GalNAc 1277:1282 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 10 63 from investigation 1606:1618 arg1 model 1673:1677 a mixed glial culture model 1651:1677 a mixed glial culture model 1651:1677 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 10 64 from role 1701:1704 arg1 neuroinflammation 1724:1740 neuroinflammation 1724:1740 neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1724:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 8 65 theme acid-binding 1320:1331 arg1 residues 1333:1340 sialic acid-binding residues 1313:1340 sialic acid-binding residues 1313:1340 This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. 36377513 4 66 theme inflammatory 612:623 arg1 model 645:649 a cytokine-driven inflammatory mixed glial culture model 594:649 a cytokine-driven inflammatory mixed glial culture model 594:649 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 10 67 theme future 1806:1811 arg1 therapeutics 1819:1830 future glyco therapeutics 1806:1830 future glyco therapeutics in neuroinflammation 1806:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 3 68 theme glycan 484:489 arg1 changes 491:497 the glycan changes 480:497 the glycan changes in these glial cells 480:518 Therefore, understating the glycan changes in these glial cells is paramount. 36377513 4 69 from phase 732:736 arg1 model 787:791 a cytokine-combination generated inflamed MGC model 741:791 a cytokine-combination generated inflamed MGC model 741:791 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 4 70 theme cytokine-driven 596:610 arg1 model 645:649 a cytokine-driven inflammatory mixed glial culture model 594:649 a cytokine-driven inflammatory mixed glial culture model 594:649 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 10 71 theme functional 1595:1604 arg1 investigation 1606:1618 the first functional investigation 1585:1618 the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1585:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 10 71 theme functional 1595:1604 arg1 study 1576:1580 The present study 1564:1580 The present study 1564:1580 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 2 72 dep inflammation 391:402 arg1 the 387:389 the 387:389 the 387:389 Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodeling from acute to chronic phases. 36377513 9 73 theme mitochondrial 1527:1539 arg1 functions 1541:1549 the mitochondrial functions 1523:1549 the mitochondrial functions 1523:1549 However, the sialyltransferase inhibitor inhibited this modification (upregulation of the sialic acid expression), which indeed modulates the mitochondrial functions. 36377513 9 74 theme acid 1482:1485 arg1 expression 1487:1496 the sialic acid expression 1471:1496 the sialic acid expression 1471:1496 However, the sialyltransferase inhibitor inhibited this modification (upregulation of the sialic acid expression), which indeed modulates the mitochondrial functions. 36377513 4 75 theme glial 631:635 arg1 model 645:649 a cytokine-driven inflammatory mixed glial culture model 594:649 a cytokine-driven inflammatory mixed glial culture model 594:649 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 10 76 theme first 1589:1593 arg1 investigation 1606:1618 the first functional investigation 1585:1618 the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1585:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 10 76 theme first 1589:1593 arg1 study 1576:1580 The present study 1564:1580 The present study 1564:1580 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 4 77 theme mixed 625:629 arg1 model 645:649 a cytokine-driven inflammatory mixed glial culture model 594:649 a cytokine-driven inflammatory mixed glial culture model 594:649 METHOD AND RESULTS A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. 36377513 10 78 from neuroinflammation 1724:1740 arg1 targets 1794:1800 identified potential therapeutic targets 1761:1800 identified potential therapeutic targets for future glyco therapeutics in neuroinflammation 1761:1851 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 10 78 from neuroinflammation 1724:1740 arg1 progression 1745:1755 progression 1745:1755 progression 1745:1755 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 10 79 theme glial 1659:1663 arg1 model 1673:1677 a mixed glial culture model 1651:1677 a mixed glial culture model 1651:1677 CONCLUSIONS The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation. 36377513 1 80 theme glial 249:253 arg1 formation 260:268 glial scar formation 249:268 glial scar formation upon spinal cord injury (SCI) 249:298 INTRODUCTION Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. 35237559 2 0 dep cytorhizophins 288:301 arg1 cytorhizophins 288:301 cytorhizophins D-E (1-2) and F-G (3-4) 288:325 cytorhizophins D-E (1-2) and F-G (3-4) 288:325 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 2 0 dep cytorhizophins 288:301 arg1 F-G 317:319 F-G 317:319 F-G (3-4) 317:325 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 2 0 dep cytorhizophins 288:301 arg1 D-E 303:305 D-E (1-2) 303:311 D-E (1-2) 303:311 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 3 1 theme first 530:534 arg1 examples 536:543 the first examples 526:543 the first examples of phthalide family 526:563 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 3 2 theme phthalide 548:556 arg1 family 558:563 phthalide family 548:563 phthalide family 548:563 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 3 3 theme family 558:563 arg1 examples 536:543 the first examples 526:543 the first examples of phthalide family 526:563 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 3 4 theme 6/6/6/5 582:588 arg1 system 607:612 fascinating 6/6/6/5 tetracyclic ring system 570:612 fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 570:681 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 5 5 theme circular 881:888 arg1 dichroism 890:898 circular dichroism 881:898 electronic circular dichroism (ECD) calculations 870:917 The partial absolute configurations of compounds 1-6 were established through electronic circular dichroism (ECD) calculations. 35237559 5 5 theme circular 881:888 arg1 ECD 901:903 ECD 901:903 ECD 901:903 The partial absolute configurations of compounds 1-6 were established through electronic circular dichroism (ECD) calculations. 35237559 6 6 theme ascorbic 1081:1088 arg1 acid 1090:1093 ascorbic acid 1081:1093 ascorbic acid (positive control) 1081:1112 Moreover, compounds 1-4 showed remarkable antioxidant activities with EC50 values ranging from 5.86 to 26.80 μM, which were better than or comparable to that of ascorbic acid (positive control). 35237559 6 6 theme ascorbic 1081:1088 arg1 control 1105:1111 positive control 1096:1111 positive control 1096:1111 Moreover, compounds 1-4 showed remarkable antioxidant activities with EC50 values ranging from 5.86 to 26.80 μM, which were better than or comparable to that of ascorbic acid (positive control). 35237559 1 7 theme known 174:178 arg1 pestacin 209:216 pestacin 209:216 pestacin 209:216 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 7 theme known 174:178 arg1 B 232:232 rhizophol B 222:232 rhizophol B 222:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 7 theme known 174:178 arg1 C 206:206 cytorhizophin C 192:206 cytorhizophin C 192:206 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 7 theme known 174:178 arg1 derivatives 180:190 three known derivatives 168:190 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B 103:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 0 8 theme Endophytic 62:71 arg1 rhizophorae 90:100 Endophytic Fungus Cytospora rhizophorae 62:100 Endophytic Fungus Cytospora rhizophorae 62:100 Antioxidant Aryl-Substituted Phthalan Derivatives Produced by Endophytic Fungus Cytospora rhizophorae. 35237559 2 9 link O-linked 455:462 arg1 unit 476:479 a highly oxygenated O-linked isopentenyl unit 435:479 a highly oxygenated O-linked isopentenyl unit 435:479 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 3 10 dep cytorhizophins 491:504 arg1 5-6 511:513 5-6 511:513 5-6 511:513 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 3 10 dep cytorhizophins 491:504 arg1 H-I 506:508 H-I 506:508 cytorhizophins H-I (5-6) 491:514 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 6 11 theme positive 1096:1103 arg1 acid 1090:1093 ascorbic acid 1081:1093 ascorbic acid (positive control) 1081:1112 Moreover, compounds 1-4 showed remarkable antioxidant activities with EC50 values ranging from 5.86 to 26.80 μM, which were better than or comparable to that of ascorbic acid (positive control). 35237559 6 11 theme positive 1096:1103 arg1 control 1105:1111 positive control 1096:1111 positive control 1096:1111 Moreover, compounds 1-4 showed remarkable antioxidant activities with EC50 values ranging from 5.86 to 26.80 μM, which were better than or comparable to that of ascorbic acid (positive control). 35237559 5 12 theme dichroism 890:898 arg1 calculations 906:917 electronic circular dichroism (ECD) calculations 870:917 electronic circular dichroism (ECD) calculations 870:917 The partial absolute configurations of compounds 1-6 were established through electronic circular dichroism (ECD) calculations. 35237559 0 13 theme Aryl-Substituted 12:27 arg1 Derivatives 38:48 Antioxidant Aryl-Substituted Phthalan Derivatives 0:48 Antioxidant Aryl-Substituted Phthalan Derivatives 0:48 Antioxidant Aryl-Substituted Phthalan Derivatives Produced by Endophytic Fungus Cytospora rhizophorae. 35237559 6 14 theme EC50 990:993 arg1 values 995:1000 EC50 values 990:1000 EC50 values ranging from 5.86 to 26.80 μM, which were better than or comparable to that of ascorbic acid (positive control) 990:1112 Moreover, compounds 1-4 showed remarkable antioxidant activities with EC50 values ranging from 5.86 to 26.80 μM, which were better than or comparable to that of ascorbic acid (positive control). 35237559 1 15 theme new 107:109 arg1 derivatives 120:130 Six new phthalan derivatives cytorhizophins D-I (1-6) 103:155 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B 103:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 16 theme cytorhizophin 192:204 arg1 C 206:206 cytorhizophin C 192:206 cytorhizophin C 192:206 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 16 theme cytorhizophin 192:204 arg1 derivatives 180:190 three known derivatives 168:190 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B 103:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 0 17 theme Antioxidant 0:10 arg1 Derivatives 38:48 Antioxidant Aryl-Substituted Phthalan Derivatives 0:48 Antioxidant Aryl-Substituted Phthalan Derivatives 0:48 Antioxidant Aryl-Substituted Phthalan Derivatives Produced by Endophytic Fungus Cytospora rhizophorae. 35237559 1 18 theme phthalan 111:118 arg1 derivatives 120:130 Six new phthalan derivatives cytorhizophins D-I (1-6) 103:155 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B 103:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 4 19 theme detail 761:766 arg1 analysis 782:789 detail spectroscopic analysis 761:789 detail spectroscopic analysis 761:789 The structures of the new phthalan derivatives were extensively confirmed by detail spectroscopic analysis. 35237559 2 20 theme diastereoisomers 345:360 arg1 pairs 336:340 two pairs 332:340 two pairs of diastereoisomers 332:360 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 5 21 theme compounds 831:839 arg1 configurations 813:826 The partial absolute configurations 792:826 The partial absolute configurations of compounds 1-6 792:843 The partial absolute configurations of compounds 1-6 were established through electronic circular dichroism (ECD) calculations. 35237559 4 22 theme derivatives 719:729 arg1 structures 688:697 The structures 684:697 The structures of the new phthalan derivatives 684:729 The structures of the new phthalan derivatives were extensively confirmed by detail spectroscopic analysis. 35237559 1 23 attach isolated 239:246 arg2 derivatives 180:190 three known derivatives 168:190 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B 103:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 23 attach isolated 239:246 arg2 derivatives 120:130 Six new phthalan derivatives cytorhizophins D-I (1-6) 103:155 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B 103:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 23 attach isolated 239:246 arg2 C 206:206 cytorhizophin C 192:206 cytorhizophin C 192:206 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 23 attach isolated 239:246 arg2 B 232:232 rhizophol B 222:232 rhizophol B 222:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 23 attach isolated 239:246 arg1 rhizophorae 263:273 rhizophorae 263:273 rhizophorae 263:273 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 23 attach isolated 239:246 arg2 pestacin 209:216 pestacin 209:216 pestacin 209:216 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 5 24 theme partial 796:802 arg1 configurations 813:826 The partial absolute configurations 792:826 The partial absolute configurations of compounds 1-6 792:843 The partial absolute configurations of compounds 1-6 were established through electronic circular dichroism (ECD) calculations. 35237559 2 25 theme 1-phenyl-1,3-dihydroisobenzofuran 387:419 arg1 scaffold 421:428 a 1-phenyl-1,3-dihydroisobenzofuran scaffold 385:428 a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit 385:479 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 0 26 theme Phthalan 29:36 arg1 Derivatives 38:48 Antioxidant Aryl-Substituted Phthalan Derivatives 0:48 Antioxidant Aryl-Substituted Phthalan Derivatives 0:48 Antioxidant Aryl-Substituted Phthalan Derivatives Produced by Endophytic Fungus Cytospora rhizophorae. 35237559 1 27 theme cytorhizophins 132:145 arg1 1-6 152:154 1-6 152:154 1-6 152:154 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 27 theme cytorhizophins 132:145 arg1 D-I 147:149 cytorhizophins D-I 132:149 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B 103:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 3 28 theme xanthen-2 653:661 arg1 skeleton 674:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 2 29 dep F-G 317:319 arg1 3-4 322:324 3-4 322:324 3-4 322:324 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 3 30 theme tetracyclic 590:600 arg1 system 607:612 fascinating 6/6/6/5 tetracyclic ring system 570:612 fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 570:681 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 2 31 theme isopentenyl 464:474 arg1 unit 476:479 a highly oxygenated O-linked isopentenyl unit 435:479 a highly oxygenated O-linked isopentenyl unit 435:479 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 3 32 theme furo 638:641 arg1 skeleton 674:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 3 33 theme ring 602:605 arg1 system 607:612 fascinating 6/6/6/5 tetracyclic ring system 570:612 fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 570:681 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 5 34 theme electronic 870:879 arg1 calculations 906:917 electronic circular dichroism (ECD) calculations 870:917 electronic circular dichroism (ECD) calculations 870:917 The partial absolute configurations of compounds 1-6 were established through electronic circular dichroism (ECD) calculations. 35237559 1 35 theme rhizophol 222:230 arg1 B 232:232 rhizophol B 222:232 rhizophol B 222:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 35 theme rhizophol 222:230 arg1 derivatives 180:190 three known derivatives 168:190 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B 103:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 2 36 theme O-linked 455:462 arg1 unit 476:479 a highly oxygenated O-linked isopentenyl unit 435:479 a highly oxygenated O-linked isopentenyl unit 435:479 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 5 37 theme absolute 804:811 arg1 configurations 813:826 The partial absolute configurations 792:826 The partial absolute configurations of compounds 1-6 792:843 The partial absolute configurations of compounds 1-6 were established through electronic circular dichroism (ECD) calculations. 35237559 0 38 theme Cytospora 80:88 arg1 rhizophorae 90:100 Endophytic Fungus Cytospora rhizophorae 62:100 Endophytic Fungus Cytospora rhizophorae 62:100 Antioxidant Aryl-Substituted Phthalan Derivatives Produced by Endophytic Fungus Cytospora rhizophorae. 35237559 3 39 theme fascinating 570:580 arg1 system 607:612 fascinating 6/6/6/5 tetracyclic ring system 570:612 fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 570:681 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 2 40 with scaffold 421:428 arg1 unit 476:479 a highly oxygenated O-linked isopentenyl unit 435:479 a highly oxygenated O-linked isopentenyl unit 435:479 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 2 41 theme oxygenated 444:453 arg1 unit 476:479 a highly oxygenated O-linked isopentenyl unit 435:479 a highly oxygenated O-linked isopentenyl unit 435:479 Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. 35237559 6 42 theme antioxidant 962:972 arg1 activities 974:983 remarkable antioxidant activities 951:983 remarkable antioxidant activities 951:983 Moreover, compounds 1-4 showed remarkable antioxidant activities with EC50 values ranging from 5.86 to 26.80 μM, which were better than or comparable to that of ascorbic acid (positive control). 35237559 3 43 theme [4,3,2-kl 643:651 arg1 skeleton 674:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 1 44 dep derivatives 180:190 arg1 pestacin 209:216 pestacin 209:216 pestacin 209:216 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 44 dep derivatives 180:190 arg1 B 232:232 rhizophol B 222:232 rhizophol B 222:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 44 dep derivatives 180:190 arg1 C 206:206 cytorhizophin C 192:206 cytorhizophin C 192:206 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 44 dep derivatives 180:190 arg1 derivatives 180:190 three known derivatives 168:190 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B 103:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 6 45 theme remarkable 951:960 arg1 activities 974:983 remarkable antioxidant activities 951:983 remarkable antioxidant activities 951:983 Moreover, compounds 1-4 showed remarkable antioxidant activities with EC50 values ranging from 5.86 to 26.80 μM, which were better than or comparable to that of ascorbic acid (positive control). 35237559 3 46 theme -one 669:672 arg1 skeleton 674:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 4 47 theme phthalan 710:717 arg1 derivatives 719:729 the new phthalan derivatives 702:729 the new phthalan derivatives 702:729 The structures of the new phthalan derivatives were extensively confirmed by detail spectroscopic analysis. 35237559 4 48 theme spectroscopic 768:780 arg1 analysis 782:789 detail spectroscopic analysis 761:789 detail spectroscopic analysis 761:789 The structures of the new phthalan derivatives were extensively confirmed by detail spectroscopic analysis. 35237559 3 49 theme unprecedented 624:636 arg1 skeleton 674:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 4 50 theme new 706:708 arg1 derivatives 719:729 the new phthalan derivatives 702:729 the new phthalan derivatives 702:729 The structures of the new phthalan derivatives were extensively confirmed by detail spectroscopic analysis. 35237559 3 51 theme 10bH 664:667 arg1 skeleton 674:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton 624:681 Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. 35237559 1 52 dep derivatives 120:130 arg1 1-6 152:154 1-6 152:154 1-6 152:154 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 1 52 dep derivatives 120:130 arg1 D-I 147:149 cytorhizophins D-I 132:149 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B 103:232 Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. 35237559 0 53 theme Fungus 73:78 arg1 rhizophorae 90:100 Endophytic Fungus Cytospora rhizophorae 62:100 Endophytic Fungus Cytospora rhizophorae 62:100 Antioxidant Aryl-Substituted Phthalan Derivatives Produced by Endophytic Fungus Cytospora rhizophorae. 35131393 0 0 theme Macaque 73:79 arg1 Mouse 66:70 the Mouse, Macaque, and Human Cerebral Cortex 62:106 Mouse 66:70 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 35131393 6 1 from located 999:1005 arg1 brains 1036:1041 mouse, macaque, and human brains 1010:1041 mouse, macaque, and human brains 1010:1041 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 7 2 theme Gs- 1211:1213 arg1 systems 1232:1238 congregated Gq/11-, Gs-, and Gi/o-linked systems 1191:1238 congregated Gq/11-, Gs-, and Gi/o-linked systems 1191:1238 We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. 35131393 1 3 theme Gi/o 220:223 arg1 subtypes 233:240 Gi/o protein subtypes 220:240 Gi/o protein subtypes 220:240 G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. 35131393 5 4 theme present 757:763 arg1 study 765:769 the present study 753:769 the present study 753:769 Using an integrative approach, the present study examined how large GPCR-subtype communities (ensembles) are expressed in different anatomical regions. 35131393 0 5 from Expression 9:18 arg1 Cortex 101:106 the Mouse, Macaque, and Human Cerebral Cortex 62:106 Cortex 101:106 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 35131393 0 5 from Expression 9:18 arg1 Mouse 66:70 the Mouse, Macaque, and Human Cerebral Cortex 62:106 Mouse 66:70 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 35131393 6 6 from brains 1036:1041 arg1 located 999:1005 located 999:1005 located 999:1005 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 3 7 theme global 491:496 arg1 organization 498:509 a global organization 489:509 a global organization of GPCRs in the brain 489:531 Although useful to explore a small number of interactions among neuromodulatory systems under controlled settings, this approach fails to account for a global organization of GPCRs in the brain. 35131393 1 8 theme protein 225:231 arg1 subtypes 233:240 Gi/o protein subtypes 220:240 Gi/o protein subtypes 220:240 G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. 35131393 7 9 theme spatial 1164:1170 arg1 correlations 1172:1183 strong spatial correlations 1157:1183 strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems 1157:1238 We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. 35131393 7 10 link Gi/o-linked 1220:1230 arg1 systems 1232:1238 congregated Gq/11-, Gs-, and Gi/o-linked systems 1191:1238 congregated Gq/11-, Gs-, and Gi/o-linked systems 1191:1238 We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. 35131393 4 11 theme signal 578:583 arg1 pathways 598:605 signal transduction pathways 578:605 signal transduction pathways 578:605 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 7 12 theme strong 1157:1162 arg1 correlations 1172:1183 strong spatial correlations 1157:1183 strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems 1157:1238 We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. 35131393 6 13 theme Brain 890:894 arg1 Atlas 896:900 the Allen Brain Atlas 880:900 the Allen Brain Atlas (http://www.brain-map.org/) 880:928 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 3 14 from organization 498:509 arg1 brain 527:531 the brain 523:531 the brain 523:531 Although useful to explore a small number of interactions among neuromodulatory systems under controlled settings, this approach fails to account for a global organization of GPCRs in the brain. 35131393 10 15 theme neuromodulatory-GPCR 1509:1528 arg1 ensembles 1530:1538 neuromodulatory-GPCR ensembles 1509:1538 neuromodulatory-GPCR ensembles 1509:1538 Well-orchestrated interactions by neuromodulatory-GPCR ensembles could be crucial for the brain to function as a highly integrated complex system. 35131393 4 16 theme individual 700:709 arg1 receptors 711:719 individual receptors 700:719 individual receptors 700:719 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 0 17 theme Cerebral 92:99 arg1 Cortex 101:106 the Mouse, Macaque, and Human Cerebral Cortex 62:106 Cortex 101:106 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 35131393 6 18 theme Allen 884:888 arg1 Atlas 896:900 the Allen Brain Atlas 880:900 the Allen Brain Atlas (http://www.brain-map.org/) 880:928 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 10 19 theme Well-orchestrated 1475:1491 arg1 interactions 1493:1504 Well-orchestrated interactions 1475:1504 Well-orchestrated interactions by neuromodulatory-GPCR ensembles 1475:1538 Well-orchestrated interactions by neuromodulatory-GPCR ensembles could be crucial for the brain to function as a highly integrated complex system. 35131393 3 20 theme GPCRs 514:518 arg1 organization 498:509 a global organization 489:509 a global organization of GPCRs in the brain 489:531 Although useful to explore a small number of interactions among neuromodulatory systems under controlled settings, this approach fails to account for a global organization of GPCRs in the brain. 35131393 9 21 theme families 1437:1444 arg1 intertwined 1462:1472 intertwined 1462:1472 intertwined 1462:1472 These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. 35131393 9 21 theme families 1437:1444 arg1 patterns 1398:1405 the expression patterns 1383:1405 the expression patterns of GPCR subtypes and receptor families 1383:1444 These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. 35131393 5 22 theme different 844:852 arg1 regions 865:871 different anatomical regions 844:871 different anatomical regions 844:871 Using an integrative approach, the present study examined how large GPCR-subtype communities (ensembles) are expressed in different anatomical regions. 35131393 0 23 theme Human 86:90 arg1 Cortex 101:106 the Mouse, Macaque, and Human Cerebral Cortex 62:106 Cortex 101:106 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 35131393 6 24 dep http 903:906 arg1 //www.brain-map.org/ 908:927 //www.brain-map.org/ 908:927 http://www.brain-map.org/ 903:927 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 3 25 theme interactions 384:395 arg1 number 374:379 a small number 366:379 a small number of interactions among neuromodulatory systems under controlled settings 366:451 Although useful to explore a small number of interactions among neuromodulatory systems under controlled settings, this approach fails to account for a global organization of GPCRs in the brain. 35131393 0 26 theme Balanced 0:7 arg1 Expression 9:18 Balanced Expression 0:18 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 0:107 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 35131393 1 27 theme brain 154:158 arg1 function 160:167 brain function 154:167 brain function 154:167 G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. 35131393 5 28 theme GPCR-subtype 790:801 arg1 communities 803:813 large GPCR-subtype communities 784:813 large GPCR-subtype communities (ensembles) 784:825 Using an integrative approach, the present study examined how large GPCR-subtype communities (ensembles) are expressed in different anatomical regions. 35131393 5 28 theme GPCR-subtype 790:801 arg1 ensembles 816:824 ensembles 816:824 ensembles 816:824 Using an integrative approach, the present study examined how large GPCR-subtype communities (ensembles) are expressed in different anatomical regions. 35131393 7 29 theme congregated 1191:1201 arg1 systems 1232:1238 congregated Gq/11-, Gs-, and Gi/o-linked systems 1191:1238 congregated Gq/11-, Gs-, and Gi/o-linked systems 1191:1238 We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. 35131393 7 30 theme Gq/11- 1203:1208 arg1 systems 1232:1238 congregated Gq/11-, Gs-, and Gi/o-linked systems 1191:1238 congregated Gq/11-, Gs-, and Gi/o-linked systems 1191:1238 We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. 35131393 10 31 theme integrated 1595:1604 arg1 system 1614:1619 a highly integrated complex system 1586:1619 a highly integrated complex system 1586:1619 Well-orchestrated interactions by neuromodulatory-GPCR ensembles could be crucial for the brain to function as a highly integrated complex system. 35131393 3 32 theme neuromodulatory 403:417 arg1 systems 419:425 neuromodulatory systems 403:425 neuromodulatory systems under controlled settings 403:451 Although useful to explore a small number of interactions among neuromodulatory systems under controlled settings, this approach fails to account for a global organization of GPCRs in the brain. 35131393 3 33 theme small 368:372 arg1 number 374:379 a small number 366:379 a small number of interactions among neuromodulatory systems under controlled settings 366:451 Although useful to explore a small number of interactions among neuromodulatory systems under controlled settings, this approach fails to account for a global organization of GPCRs in the brain. 35131393 6 34 theme expression 952:961 arg1 energy 963:968 the mRNA expression energy 943:968 the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains 943:1041 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 6 35 dep Atlas 896:900 arg1 http 903:906 http 903:906 http://www.brain-map.org/ 903:927 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 5 36 theme anatomical 854:863 arg1 regions 865:871 different anatomical regions 844:871 different anatomical regions 844:871 Using an integrative approach, the present study examined how large GPCR-subtype communities (ensembles) are expressed in different anatomical regions. 35131393 6 37 theme human 1030:1034 arg1 brains 1036:1041 mouse, macaque, and human brains 1010:1041 mouse, macaque, and human brains 1010:1041 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 7 38 theme cortical 1128:1135 arg1 regions 1137:1143 all cortical regions 1124:1143 all cortical regions 1124:1143 We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. 35131393 6 39 theme mRNA 947:950 arg1 energy 963:968 the mRNA expression energy 943:968 the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains 943:1041 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 7 40 theme heterogeneous 1079:1091 arg1 expression 1093:1102 a heterogeneous expression 1077:1102 a heterogeneous expression of GPCR-mRNA 1077:1115 We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. 35131393 4 41 located present 611:617 arg1 cells 629:633 single cells 622:633 single cells 622:633 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 4 41 located present 611:617 arg2 pathways 598:605 signal transduction pathways 578:605 signal transduction pathways 578:605 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 4 41 located present 611:617 arg2 receptors 564:572 multiple receptors 555:572 multiple receptors 555:572 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 4 42 from cells 629:633 arg1 present 611:617 present 611:617 present 611:617 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 4 43 theme single 622:627 arg1 cells 629:633 single cells 622:633 single cells 622:633 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 10 44 theme complex 1606:1612 arg1 system 1614:1619 a highly integrated complex system 1586:1619 a highly integrated complex system 1586:1619 Well-orchestrated interactions by neuromodulatory-GPCR ensembles could be crucial for the brain to function as a highly integrated complex system. 35131393 8 45 theme corresponding 1333:1345 arg1 groups 1347:1352 their corresponding groups 1327:1352 their corresponding groups 1327:1352 Correlation strength increased with age but dropped when randomly removing genes from their corresponding groups. 35131393 4 46 theme GPCRs 679:683 arg1 GPCRs 679:683 GPCRs 679:683 GPCRs 679:683 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 4 46 theme GPCRs 679:683 arg1 groups 669:674 groups 669:674 groups of GPCRs 669:683 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 9 47 theme subtypes 1415:1422 arg1 intertwined 1462:1472 intertwined 1462:1472 intertwined 1462:1472 These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. 35131393 9 47 theme subtypes 1415:1422 arg1 patterns 1398:1405 the expression patterns 1383:1405 the expression patterns of GPCR subtypes and receptor families 1383:1444 These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. 35131393 0 48 theme Receptor 41:48 arg1 Subtypes 50:57 G Protein-coupled Receptor Subtypes 23:57 G Protein-coupled Receptor Subtypes 23:57 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 35131393 6 49 theme macaque 1017:1023 arg1 mouse 1010:1014 mouse 1010:1014 mouse 1010:1014 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 1 50 theme heterotrimeric 190:203 arg1 Gq/11 205:209 heterotrimeric Gq/11 190:209 heterotrimeric Gq/11 190:209 G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. 35131393 0 51 theme Protein-coupled 25:39 arg1 Subtypes 50:57 G Protein-coupled Receptor Subtypes 23:57 G Protein-coupled Receptor Subtypes 23:57 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 35131393 4 52 theme multiple 555:562 arg1 receptors 564:572 multiple receptors 555:572 multiple receptors 555:572 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 6 53 theme hundreds 973:980 arg1 energy 963:968 the mRNA expression energy 943:968 the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains 943:1041 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 5 54 theme integrative 731:741 arg1 approach 743:750 an integrative approach 728:750 an integrative approach 728:750 Using an integrative approach, the present study examined how large GPCR-subtype communities (ensembles) are expressed in different anatomical regions. 35131393 9 55 theme receptor 1428:1435 arg1 families 1437:1444 receptor families 1428:1444 receptor families 1428:1444 These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. 35131393 5 56 theme large 784:788 arg1 communities 803:813 large GPCR-subtype communities 784:813 large GPCR-subtype communities (ensembles) 784:825 Using an integrative approach, the present study examined how large GPCR-subtype communities (ensembles) are expressed in different anatomical regions. 35131393 5 56 theme large 784:788 arg1 ensembles 816:824 ensembles 816:824 ensembles 816:824 Using an integrative approach, the present study examined how large GPCR-subtype communities (ensembles) are expressed in different anatomical regions. 35131393 0 57 theme Subtypes 50:57 arg1 Expression 9:18 Balanced Expression 0:18 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 0:107 Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex. 35131393 4 58 attach present 611:617 arg1 cells 629:633 single cells 622:633 single cells 622:633 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 4 58 attach present 611:617 arg2 pathways 598:605 signal transduction pathways 578:605 signal transduction pathways 578:605 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 4 58 attach present 611:617 arg2 receptors 564:572 multiple receptors 555:572 multiple receptors 555:572 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 2 59 theme cell-by-cell 318:329 arg1 basis 332:336 a 'cell-by-cell' basis 315:336 a 'cell-by-cell' basis 315:336 Researchers frequently study neuromodulation via these GPCR-subtypes on a 'cell-by-cell' basis. 35131393 7 60 theme GPCR-mRNA 1107:1115 arg1 expression 1093:1102 a heterogeneous expression 1077:1102 a heterogeneous expression of GPCR-mRNA 1077:1115 We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. 35131393 1 61 theme G-protein 109:117 arg1 GPCRs 138:142 GPCRs 138:142 GPCRs 138:142 G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. 35131393 1 61 theme G-protein 109:117 arg1 receptors 127:135 G-protein coupled receptors 109:135 G-protein coupled receptors (GPCRs) 109:143 G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. 35131393 6 62 theme mouse 1010:1014 arg1 brains 1036:1041 mouse, macaque, and human brains 1010:1041 mouse, macaque, and human brains 1010:1041 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 1 63 theme coupled 119:125 arg1 GPCRs 138:142 GPCRs 138:142 GPCRs 138:142 G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. 35131393 1 63 theme coupled 119:125 arg1 receptors 127:135 G-protein coupled receptors 109:135 G-protein coupled receptors (GPCRs) 109:143 G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. 35131393 4 64 theme transduction 585:596 arg1 pathways 598:605 signal transduction pathways 578:605 signal transduction pathways 578:605 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 4 65 from present 611:617 arg1 cells 629:633 single cells 622:633 single cells 622:633 Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. 35131393 8 66 theme Correlation 1241:1251 arg1 strength 1253:1260 Correlation strength 1241:1260 Correlation strength 1241:1260 Correlation strength increased with age but dropped when randomly removing genes from their corresponding groups. 35131393 3 67 theme controlled 433:442 arg1 settings 444:451 controlled settings 433:451 controlled settings 433:451 Although useful to explore a small number of interactions among neuromodulatory systems under controlled settings, this approach fails to account for a global organization of GPCRs in the brain. 35131393 6 68 theme located 999:1005 arg1 hundreds 973:980 hundreds 973:980 hundreds of GPCR-subtypes located in mouse, macaque, and human brains 973:1041 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35131393 9 69 theme GPCR 1410:1413 arg1 subtypes 1415:1422 GPCR subtypes 1410:1422 GPCR subtypes 1410:1422 These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. 35131393 9 70 theme expression 1387:1396 arg1 intertwined 1462:1472 intertwined 1462:1472 intertwined 1462:1472 These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. 35131393 9 70 theme expression 1387:1396 arg1 patterns 1398:1405 the expression patterns 1383:1405 the expression patterns of GPCR subtypes and receptor families 1383:1444 These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. 35131393 7 71 theme Gi/o-linked 1220:1230 arg1 systems 1232:1238 congregated Gq/11-, Gs-, and Gi/o-linked systems 1191:1238 congregated Gq/11-, Gs-, and Gi/o-linked systems 1191:1238 We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. 35131393 6 72 theme GPCR-subtypes 985:997 arg1 hundreds 973:980 hundreds 973:980 hundreds of GPCR-subtypes located in mouse, macaque, and human brains 973:1041 Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. 35871308 5 0 theme volume 814:819 arg1 technique 837:845 Large volume sample stacking technique 808:845 Large volume sample stacking technique for sample injection 808:866 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 7 1 theme great 1242:1246 arg1 application 1258:1268 great potential application 1242:1268 great potential application in clinical diagnosis of O-GlcNAc-related diseases 1242:1319 Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 35871308 5 2 theme fluorescence 881:892 arg1 system 905:910 a unique fluorescence collection system 872:910 a unique fluorescence collection system for LIF detection 872:928 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 2 3 theme robust 355:360 arg1 method 376:381 a robust and sensitive method 353:381 a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method 353:473 Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. 35871308 5 4 theme sample 821:826 arg1 technique 837:845 Large volume sample stacking technique 808:845 Large volume sample stacking technique for sample injection 808:866 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 6 5 theme clinical 1126:1133 arg1 samples 1141:1147 clinical blood samples 1126:1147 clinical blood samples with satisfactory accuracy 1126:1174 The method is successfully applied to detect OGT activity in clinical blood samples with satisfactory accuracy. 35871308 3 6 theme OGT-catalyzed 560:572 arg1 reaction 574:581 OGT-catalyzed reaction 560:581 OGT-catalyzed reaction 560:581 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 5 7 theme detection 1008:1016 arg1 limit 999:1003 a low limit 993:1003 a low limit of detection down to 0.23 pM for OGT detection 993:1050 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 1 8 link O-linked 105:112 arg1 O-GlcNAc 135:142 O-GlcNAc 135:142 O-GlcNAc 135:142 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 1 8 link O-linked 105:112 arg1 N-acetylglucosamine 114:132 O-linked N-acetylglucosamine 105:132 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 105:161 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 3 9 contain containing 500:509 arg1 peptide 492:498 AF-488-modified peptide 476:498 AF-488-modified peptide containing serine active group 476:529 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 3 9 contain containing 500:509 arg2 group 525:529 serine active group 511:529 serine active group 511:529 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 3 9 contain containing 500:509 arg1 substrate 546:554 substrate 546:554 substrate 546:554 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 5 10 dep 0.23 1026:1029 arg1 to 1023:1024 to 1023:1024 to 1023:1024 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 4 11 theme quantitative 731:742 arg1 determination 744:756 quantitative determination 731:756 quantitative determination of glycosylated peptide produced by the reaction 731:805 The enzyme activity of OGT is measured by quantitative determination of glycosylated peptide produced by the reaction. 35871308 5 12 theme LIF 916:918 arg1 detection 920:928 LIF detection 916:928 LIF detection 916:928 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 5 13 theme detection 965:973 arg1 sensitivity 975:985 the detection sensitivity 961:985 the detection sensitivity 961:985 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 5 14 theme collection 894:903 arg1 system 905:910 a unique fluorescence collection system 872:910 a unique fluorescence collection system for LIF detection 872:928 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 3 15 theme AF-488-modified 476:490 arg1 peptide 492:498 AF-488-modified peptide 476:498 AF-488-modified peptide containing serine active group 476:529 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 3 15 theme AF-488-modified 476:490 arg1 substrate 546:554 substrate 546:554 substrate 546:554 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 2 16 theme assay 391:395 arg1 based 397:401 OGT assay based 387:401 OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method 387:473 Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. 35871308 5 17 theme sample 851:856 arg1 injection 858:866 sample injection 851:866 sample injection 851:866 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 6 18 with samples 1141:1147 arg1 accuracy 1167:1174 satisfactory accuracy 1154:1174 satisfactory accuracy 1154:1174 The method is successfully applied to detect OGT activity in clinical blood samples with satisfactory accuracy. 35871308 1 19 gly glycosylation 213:225 arg1 biomolecules 230:241 biomolecules 230:241 biomolecules 230:241 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 1 19 gly glycosylation 213:225 arg1 diseases 255:262 various diseases 247:262 various diseases 247:262 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 1 20 theme O-linked 105:112 arg1 O-GlcNAc 135:142 O-GlcNAc 135:142 O-GlcNAc 135:142 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 1 20 theme O-linked 105:112 arg1 N-acetylglucosamine 114:132 O-linked N-acetylglucosamine 105:132 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 105:161 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 2 21 theme OGT 387:389 arg1 based 397:401 OGT assay based 387:401 OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method 387:473 Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. 35871308 2 22 theme CE-LIF 460:465 arg1 method 468:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. 35871308 7 23 theme potential 1248:1256 arg1 application 1258:1268 great potential application 1242:1268 great potential application in clinical diagnosis of O-GlcNAc-related diseases 1242:1319 Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 35871308 7 24 theme O-GlcNAc-related 1295:1310 arg1 diseases 1312:1319 O-GlcNAc-related diseases 1295:1319 O-GlcNAc-related diseases 1295:1319 Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 35871308 1 25 theme N-acetylglucosamine 114:132 arg1 OGT 158:160 OGT 158:160 OGT 158:160 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 1 25 theme N-acetylglucosamine 114:132 arg1 transferase 145:155 O-linked N-acetylglucosamine (O-GlcNAc) transferase 105:155 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 105:161 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 7 26 theme accurate 1206:1213 arg1 method 1230:1235 a simple, accurate, and sensitive method 1196:1235 a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases 1196:1319 Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 35871308 4 27 theme OGT 712:714 arg1 activity 700:707 The enzyme activity 689:707 The enzyme activity of OGT 689:714 The enzyme activity of OGT is measured by quantitative determination of glycosylated peptide produced by the reaction. 35871308 0 28 theme Ultrasensitive 0:13 arg1 assay 15:19 Ultrasensitive assay 0:19 Ultrasensitive assay of O-GlcNAc transferase using capillary electrophoresis-laser 0:81 Ultrasensitive assay of O-GlcNAc transferase using capillary electrophoresis-laser induced fluorescence. 35871308 5 29 theme low 995:997 arg1 limit 999:1003 a low limit 993:1003 a low limit of detection down to 0.23 pM for OGT detection 993:1050 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 1 30 theme O-GlcNAc 204:211 arg1 glycosylation 213:225 O-GlcNAc glycosylation 204:225 O-GlcNAc glycosylation of biomolecules and various diseases 204:262 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 0 31 theme O-GlcNAc 24:31 arg1 transferase 33:43 O-GlcNAc transferase 24:43 O-GlcNAc transferase 24:43 Ultrasensitive assay of O-GlcNAc transferase using capillary electrophoresis-laser induced fluorescence. 35871308 5 32 dep detection 1008:1016 arg1 pM 1031:1032 pM 1031:1032 pM 1031:1032 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 6 33 theme OGT 1110:1112 arg1 activity 1114:1121 OGT activity 1110:1121 OGT activity 1110:1121 The method is successfully applied to detect OGT activity in clinical blood samples with satisfactory accuracy. 35871308 2 34 theme electrophoresis-laser 416:436 arg1 method 468:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. 35871308 2 35 theme induced 438:444 arg1 method 468:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. 35871308 1 36 theme promising 292:300 arg1 target 328:333 a promising potential new therapeutic target 290:333 a promising potential new therapeutic target 290:333 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 1 36 theme promising 292:300 arg1 it 269:270 it 269:270 it 269:270 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 2 37 theme capillary 406:414 arg1 method 468:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. 35871308 5 38 theme stacking 828:835 arg1 technique 837:845 Large volume sample stacking technique 808:845 Large volume sample stacking technique for sample injection 808:866 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 1 39 theme potential 302:310 arg1 target 328:333 a promising potential new therapeutic target 290:333 a promising potential new therapeutic target 290:333 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 1 39 theme potential 302:310 arg1 it 269:270 it 269:270 it 269:270 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 4 40 gly glycosylated 761:772 arg1 peptide 774:780 glycosylated peptide 761:780 glycosylated peptide produced by the reaction 761:805 The enzyme activity of OGT is measured by quantitative determination of glycosylated peptide produced by the reaction. 35871308 5 41 dep pM 1031:1032 arg1 0.23 1026:1029 0.23 1026:1029 0.23 1026:1029 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 2 42 from based 397:401 arg1 method 468:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. 35871308 1 43 theme biomolecules 230:241 arg1 glycosylation 213:225 O-GlcNAc glycosylation 204:225 O-GlcNAc glycosylation of biomolecules and various diseases 204:262 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 0 44 theme transferase 33:43 arg1 assay 15:19 Ultrasensitive assay 0:19 Ultrasensitive assay of O-GlcNAc transferase using capillary electrophoresis-laser 0:81 Ultrasensitive assay of O-GlcNAc transferase using capillary electrophoresis-laser induced fluorescence. 35871308 1 45 theme new 312:314 arg1 target 328:333 a promising potential new therapeutic target 290:333 a promising potential new therapeutic target 290:333 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 1 45 theme new 312:314 arg1 it 269:270 it 269:270 it 269:270 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 3 46 theme glycosylation 661:673 arg1 modification 675:686 O-GlcNAc glycosylation modification 652:686 O-GlcNAc glycosylation modification 652:686 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 2 47 theme fluorescence 446:457 arg1 method 468:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 capillary electrophoresis-laser induced fluorescence (CE-LIF) method 406:473 Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. 35871308 7 48 theme simple 1198:1203 arg1 method 1230:1235 a simple, accurate, and sensitive method 1196:1235 a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases 1196:1319 Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 35871308 1 49 theme therapeutic 316:326 arg1 target 328:333 a promising potential new therapeutic target 290:333 a promising potential new therapeutic target 290:333 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 1 49 theme therapeutic 316:326 arg1 it 269:270 it 269:270 it 269:270 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 7 50 with method 1230:1235 arg1 application 1258:1268 great potential application 1242:1268 great potential application in clinical diagnosis of O-GlcNAc-related diseases 1242:1319 Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 35871308 6 51 theme satisfactory 1154:1165 arg1 accuracy 1167:1174 satisfactory accuracy 1154:1174 satisfactory accuracy 1154:1174 The method is successfully applied to detect OGT activity in clinical blood samples with satisfactory accuracy. 35871308 3 52 theme serine 511:516 arg1 group 525:529 serine active group 511:529 serine active group 511:529 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 0 53 theme capillary 51:59 arg1 electrophoresis-laser 61:81 capillary electrophoresis-laser 51:81 capillary electrophoresis-laser 51:81 Ultrasensitive assay of O-GlcNAc transferase using capillary electrophoresis-laser induced fluorescence. 35871308 7 54 theme sensitive 1220:1228 arg1 method 1230:1235 a simple, accurate, and sensitive method 1196:1235 a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases 1196:1319 Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 35871308 3 55 theme active 518:523 arg1 group 525:529 serine active group 511:529 serine active group 511:529 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 3 56 theme nonradioactive 588:601 arg1 donor 635:639 sugar donor 629:639 sugar donor 629:639 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 3 56 theme nonradioactive 588:601 arg1 UDP-GlcNAc 603:612 nonradioactive UDP-GlcNAc 588:612 nonradioactive UDP-GlcNAc 588:612 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 3 57 theme sugar 629:633 arg1 donor 635:639 sugar donor 629:639 sugar donor 629:639 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 3 57 theme sugar 629:633 arg1 UDP-GlcNAc 603:612 nonradioactive UDP-GlcNAc 588:612 nonradioactive UDP-GlcNAc 588:612 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 4 58 theme peptide 774:780 arg1 determination 744:756 quantitative determination 731:756 quantitative determination of glycosylated peptide produced by the reaction 731:805 The enzyme activity of OGT is measured by quantitative determination of glycosylated peptide produced by the reaction. 35871308 1 59 theme various 247:253 arg1 diseases 255:262 various diseases 247:262 various diseases 247:262 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 7 60 from application 1258:1268 arg1 diagnosis 1282:1290 clinical diagnosis 1273:1290 clinical diagnosis of O-GlcNAc-related diseases 1273:1319 Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 35871308 3 61 theme O-GlcNAc 652:659 arg1 modification 675:686 O-GlcNAc glycosylation modification 652:686 O-GlcNAc glycosylation modification 652:686 AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. 35871308 4 62 theme glycosylated 761:772 arg1 peptide 774:780 glycosylated peptide 761:780 glycosylated peptide produced by the reaction 761:805 The enzyme activity of OGT is measured by quantitative determination of glycosylated peptide produced by the reaction. 35871308 1 63 theme diseases 255:262 arg1 glycosylation 213:225 O-GlcNAc glycosylation 204:225 O-GlcNAc glycosylation of biomolecules and various diseases 204:262 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 5 64 theme OGT 1038:1040 arg1 detection 1042:1050 OGT detection 1038:1050 OGT detection 1038:1050 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 1 65 theme glycosylation 213:225 arg1 level 195:199 the level 191:199 the level of O-GlcNAc glycosylation of biomolecules and various diseases 191:262 O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. 35871308 2 66 theme sensitive 366:374 arg1 method 376:381 a robust and sensitive method 353:381 a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method 353:473 Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. 35871308 4 67 theme enzyme 693:698 arg1 activity 700:707 The enzyme activity 689:707 The enzyme activity of OGT 689:714 The enzyme activity of OGT is measured by quantitative determination of glycosylated peptide produced by the reaction. 35871308 5 68 theme Large 808:812 arg1 technique 837:845 Large volume sample stacking technique 808:845 Large volume sample stacking technique for sample injection 808:866 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 5 69 theme unique 874:879 arg1 system 905:910 a unique fluorescence collection system 872:910 a unique fluorescence collection system for LIF detection 872:928 Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. 35871308 7 70 theme diseases 1312:1319 arg1 diagnosis 1282:1290 clinical diagnosis 1273:1290 clinical diagnosis of O-GlcNAc-related diseases 1273:1319 Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 35871308 6 71 theme blood 1135:1139 arg1 samples 1141:1147 clinical blood samples 1126:1147 clinical blood samples with satisfactory accuracy 1126:1174 The method is successfully applied to detect OGT activity in clinical blood samples with satisfactory accuracy. 35871308 7 72 theme clinical 1273:1280 arg1 diagnosis 1282:1290 clinical diagnosis 1273:1290 clinical diagnosis of O-GlcNAc-related diseases 1273:1319 Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 35588599 9 0 from promising 1430:1438 arg1 treatment 1473:1481 the treatment 1469:1481 the treatment of AD 1469:1487 Together, these findings suggest that 39 was promising as a potent OGA inhibitor in the treatment of AD. 35588599 3 1 theme O-GlcNAcylation 511:525 arg1 levels 497:502 the levels 493:502 the levels of tau O-GlcNAcylation 493:525 Therefore, preventing tau hyperphosphorylation by increasing the levels of tau O-GlcNAcylation via OGA inhibitors could be a promising approach. 35588599 7 2 theme Aβ 1209:1210 arg1 concentrations 1213:1226 amyloid-β (Aβ) concentrations 1198:1226 amyloid-β (Aβ) concentrations 1198:1226 In addition, 39 restored the cognitive function in mice and reduced amyloid-β (Aβ) concentrations to a greater extent than Thiamet-G. 35588599 9 3 theme potent 1445:1450 arg1 inhibitor 1456:1464 a potent OGA inhibitor 1443:1464 a potent OGA inhibitor 1443:1464 Together, these findings suggest that 39 was promising as a potent OGA inhibitor in the treatment of AD. 35588599 5 4 theme excellent 897:905 arg1 inhibition 911:920 excellent OGA inhibition 897:920 excellent OGA inhibition 897:920 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 5 4 theme excellent 897:905 arg1 cytotoxicity 926:937 no cytotoxicity 923:937 no cytotoxicity 923:937 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 5 5 theme OGA 907:909 arg1 inhibition 911:920 excellent OGA inhibition 897:920 excellent OGA inhibition 897:920 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 5 5 theme OGA 907:909 arg1 cytotoxicity 926:937 no cytotoxicity 923:937 no cytotoxicity 923:937 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 6 6 theme model 993:997 arg1 mice 999:1002 acute AD model mice 984:1002 acute AD model mice 984:1002 In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. 35588599 3 7 theme OGA 531:533 arg1 inhibitors 535:544 OGA inhibitors 531:544 OGA inhibitors 531:544 Therefore, preventing tau hyperphosphorylation by increasing the levels of tau O-GlcNAcylation via OGA inhibitors could be a promising approach. 35588599 5 8 theme pharmacokinetic 953:967 arg1 properties 969:978 good pharmacokinetic properties 948:978 good pharmacokinetic properties 948:978 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 5 9 theme good 948:951 arg1 properties 969:978 good pharmacokinetic properties 948:978 good pharmacokinetic properties 948:978 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 4 10 theme potent 599:604 arg1 inhibitor 610:618 a potent OGA inhibitor 597:618 a potent OGA inhibitor 597:618 Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. 35588599 4 10 theme potent 599:604 arg1 Thiamet-G 586:594 Thiamet-G 586:594 Thiamet-G 586:594 Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. 35588599 7 11 theme amyloid-β 1198:1206 arg1 concentrations 1213:1226 amyloid-β (Aβ) concentrations 1198:1226 amyloid-β (Aβ) concentrations 1198:1226 In addition, 39 restored the cognitive function in mice and reduced amyloid-β (Aβ) concentrations to a greater extent than Thiamet-G. 35588599 3 12 theme promising 557:565 arg1 approach 567:574 a promising approach 555:574 a promising approach 555:574 Therefore, preventing tau hyperphosphorylation by increasing the levels of tau O-GlcNAcylation via OGA inhibitors could be a promising approach. 35588599 6 13 theme acute 984:988 arg1 mice 999:1002 acute AD model mice 984:1002 acute AD model mice 984:1002 In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. 35588599 7 14 theme greater 1233:1239 arg1 extent 1241:1246 a greater extent 1231:1246 a greater extent than Thiamet-G 1231:1261 In addition, 39 restored the cognitive function in mice and reduced amyloid-β (Aβ) concentrations to a greater extent than Thiamet-G. 35588599 8 15 theme docking 1274:1280 arg1 studies 1282:1288 Molecular docking studies 1264:1288 Molecular docking studies 1264:1288 Molecular docking studies demonstrated that 39 was well associated with OGA through H-bonds and hydrophobic interaction. 35588599 2 16 theme tau 272:274 arg1 O-GlcNAcylation 253:267 O-GlcNAcylation 253:267 O-GlcNAcylation of tau 253:274 O-GlcNAcylation of tau can negatively regulate hyperphosphorylation and the O-GlcNAcase (OGA) catalyzes the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein. 35588599 2 17 theme β-N-acetylglucosamine 381:401 arg1 removal 361:367 the removal 357:367 the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein 357:429 O-GlcNAcylation of tau can negatively regulate hyperphosphorylation and the O-GlcNAcase (OGA) catalyzes the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein. 35588599 6 18 theme attributable 1069:1080 arg1 activity 1060:1067 OGA activity 1056:1067 OGA activity attributable to its better blood-brain barrier permeability 1056:1127 In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. 35588599 5 19 theme Further 787:793 arg1 optimization 804:815 Further chemical optimization 787:815 Further chemical optimization 787:815 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 5 20 theme chemical 795:802 arg1 optimization 804:815 Further chemical optimization 787:815 Further chemical optimization 787:815 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 6 21 from mice 999:1002 arg1 effective 1017:1025 effective 1017:1025 effective 1017:1025 In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. 35588599 6 22 from effective 1017:1025 arg1 mice 999:1002 acute AD model mice 984:1002 acute AD model mice 984:1002 In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. 35588599 4 23 theme hit 718:720 arg1 7j 731:732 hit compound 7j 718:732 hit compound 7j 718:732 Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. 35588599 1 24 theme tau 187:189 arg1 protein 191:197 tau protein 187:197 tau protein 187:197 The neurofibrillary tangles (NFTs) formed from hyperphosphorylation of tau protein are closely associated with Alzheimer's disease (AD). 35588599 0 25 theme Structure-based 0:14 arg1 discovery 16:24 Structure-based discovery 0:24 Structure-based discovery 0:24 Structure-based discovery and development of novel O-GlcNAcase inhibitors for the treatment of Alzheimer's disease. 35588599 9 26 from treatment 1473:1481 arg1 promising 1430:1438 promising 1430:1438 promising 1430:1438 Together, these findings suggest that 39 was promising as a potent OGA inhibitor in the treatment of AD. 35588599 2 27 theme O-linked 372:379 arg1 O-GlcNAc 404:411 O-GlcNAc 404:411 O-GlcNAc 404:411 O-GlcNAcylation of tau can negatively regulate hyperphosphorylation and the O-GlcNAcase (OGA) catalyzes the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein. 35588599 2 27 theme O-linked 372:379 arg1 β-N-acetylglucosamine 381:401 O-linked β-N-acetylglucosamine 372:401 O-linked β-N-acetylglucosamine (O-GlcNAc) 372:412 O-GlcNAcylation of tau can negatively regulate hyperphosphorylation and the O-GlcNAcase (OGA) catalyzes the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein. 35588599 5 28 theme 7j 844:845 arg1 structure 847:855 the 7j structure 840:855 the 7j structure 840:855 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 5 29 contain has 944:946 arg2 properties 969:978 good pharmacokinetic properties 948:978 good pharmacokinetic properties 948:978 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 5 29 contain has 944:946 arg1 compound 869:876 compound 39 869:879 compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties 869:978 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 4 30 theme binding 629:635 arg1 mode 637:640 its binding mode 625:640 its binding mode to OGA 625:647 Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. 35588599 7 31 theme cognitive 1159:1167 arg1 function 1169:1176 the cognitive function 1155:1176 the cognitive function 1155:1176 In addition, 39 restored the cognitive function in mice and reduced amyloid-β (Aβ) concentrations to a greater extent than Thiamet-G. 35588599 4 32 theme compound 722:729 arg1 7j 731:732 hit compound 7j 718:732 hit compound 7j 718:732 Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. 35588599 2 33 theme tau 419:421 arg1 protein 423:429 tau protein 419:429 tau protein 419:429 O-GlcNAcylation of tau can negatively regulate hyperphosphorylation and the O-GlcNAcase (OGA) catalyzes the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein. 35588599 0 34 theme novel 45:49 arg1 inhibitors 63:72 novel O-GlcNAcase inhibitors 45:72 novel O-GlcNAcase inhibitors for the treatment of Alzheimer's disease 45:113 Structure-based discovery and development of novel O-GlcNAcase inhibitors for the treatment of Alzheimer's disease. 35588599 3 35 theme tau 507:509 arg1 O-GlcNAcylation 511:525 tau O-GlcNAcylation 507:525 tau O-GlcNAcylation 507:525 Therefore, preventing tau hyperphosphorylation by increasing the levels of tau O-GlcNAcylation via OGA inhibitors could be a promising approach. 35588599 2 36 link O-linked 372:379 arg1 O-GlcNAc 404:411 O-GlcNAc 404:411 O-GlcNAc 404:411 O-GlcNAcylation of tau can negatively regulate hyperphosphorylation and the O-GlcNAcase (OGA) catalyzes the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein. 35588599 2 36 link O-linked 372:379 arg1 β-N-acetylglucosamine 381:401 O-linked β-N-acetylglucosamine 372:401 O-linked β-N-acetylglucosamine (O-GlcNAc) 372:412 O-GlcNAcylation of tau can negatively regulate hyperphosphorylation and the O-GlcNAcase (OGA) catalyzes the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein. 35588599 1 37 theme protein 191:197 arg1 hyperphosphorylation 163:182 hyperphosphorylation 163:182 hyperphosphorylation of tau protein 163:197 The neurofibrillary tangles (NFTs) formed from hyperphosphorylation of tau protein are closely associated with Alzheimer's disease (AD). 35588599 3 38 theme tau 454:456 arg1 hyperphosphorylation 458:477 tau hyperphosphorylation 454:477 tau hyperphosphorylation 454:477 Therefore, preventing tau hyperphosphorylation by increasing the levels of tau O-GlcNAcylation via OGA inhibitors could be a promising approach. 35588599 6 39 theme OGA 1056:1058 arg1 activity 1060:1067 OGA activity 1056:1067 OGA activity attributable to its better blood-brain barrier permeability 1056:1127 In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. 35588599 8 40 theme Molecular 1264:1272 arg1 studies 1282:1288 Molecular docking studies 1264:1288 Molecular docking studies 1264:1288 Molecular docking studies demonstrated that 39 was well associated with OGA through H-bonds and hydrophobic interaction. 35588599 5 41 theme structure 847:855 arg1 optimization 804:815 Further chemical optimization 787:815 Further chemical optimization 787:815 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 5 41 theme structure 847:855 arg1 diversification 821:835 diversification 821:835 diversification 821:835 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 0 42 theme inhibitors 63:72 arg1 development 30:40 development 30:40 development of novel O-GlcNAcase inhibitors for the treatment of Alzheimer's disease 30:113 Structure-based discovery and development of novel O-GlcNAcase inhibitors for the treatment of Alzheimer's disease. 35588599 0 42 theme inhibitors 63:72 arg1 discovery 16:24 Structure-based discovery 0:24 Structure-based discovery 0:24 Structure-based discovery and development of novel O-GlcNAcase inhibitors for the treatment of Alzheimer's disease. 35588599 4 43 theme novel 652:656 arg1 scaffold 672:679 a novel OGA inhibitor scaffold 650:679 a novel OGA inhibitor scaffold bearing three parts 650:699 Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. 35588599 8 44 theme hydrophobic 1360:1370 arg1 interaction 1372:1382 hydrophobic interaction 1360:1382 hydrophobic interaction 1360:1382 Molecular docking studies demonstrated that 39 was well associated with OGA through H-bonds and hydrophobic interaction. 35588599 6 45 theme blood-brain 1096:1106 arg1 permeability 1116:1127 its better blood-brain barrier permeability 1085:1127 its better blood-brain barrier permeability 1085:1127 In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. 35588599 0 46 theme O-GlcNAcase 51:61 arg1 inhibitors 63:72 novel O-GlcNAcase inhibitors 45:72 novel O-GlcNAcase inhibitors for the treatment of Alzheimer's disease 45:113 Structure-based discovery and development of novel O-GlcNAcase inhibitors for the treatment of Alzheimer's disease. 35588599 1 47 theme neurofibrillary 120:134 arg1 tangles 136:142 The neurofibrillary tangles 116:142 The neurofibrillary tangles (NFTs) formed from hyperphosphorylation of tau protein 116:197 The neurofibrillary tangles (NFTs) formed from hyperphosphorylation of tau protein are closely associated with Alzheimer's disease (AD). 35588599 1 47 theme neurofibrillary 120:134 arg1 NFTs 145:148 NFTs 145:148 NFTs 145:148 The neurofibrillary tangles (NFTs) formed from hyperphosphorylation of tau protein are closely associated with Alzheimer's disease (AD). 35588599 9 48 theme AD 1486:1487 arg1 treatment 1473:1481 the treatment 1469:1481 the treatment of AD 1469:1487 Together, these findings suggest that 39 was promising as a potent OGA inhibitor in the treatment of AD. 35588599 5 49 contain possesses 887:895 arg2 cytotoxicity 926:937 no cytotoxicity 923:937 no cytotoxicity 923:937 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 5 49 contain possesses 887:895 arg1 compound 869:876 compound 39 869:879 compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties 869:978 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 5 49 contain possesses 887:895 arg2 inhibition 911:920 excellent OGA inhibition 897:920 excellent OGA inhibition 897:920 Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. 35588599 6 50 theme barrier 1108:1114 arg1 permeability 1116:1127 its better blood-brain barrier permeability 1085:1127 its better blood-brain barrier permeability 1085:1127 In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. 35588599 4 51 theme OGA 606:608 arg1 inhibitor 610:618 a potent OGA inhibitor 597:618 a potent OGA inhibitor 597:618 Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. 35588599 4 51 theme OGA 606:608 arg1 Thiamet-G 586:594 Thiamet-G 586:594 Thiamet-G 586:594 Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. 35588599 6 52 theme better 1089:1094 arg1 permeability 1116:1127 its better blood-brain barrier permeability 1085:1127 its better blood-brain barrier permeability 1085:1127 In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. 35588599 9 53 theme OGA 1452:1454 arg1 inhibitor 1456:1464 a potent OGA inhibitor 1443:1464 a potent OGA inhibitor 1443:1464 Together, these findings suggest that 39 was promising as a potent OGA inhibitor in the treatment of AD. 35588599 4 54 theme inhibitor 662:670 arg1 scaffold 672:679 a novel OGA inhibitor scaffold 650:679 a novel OGA inhibitor scaffold bearing three parts 650:699 Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. 35588599 6 55 theme AD 990:991 arg1 mice 999:1002 acute AD model mice 984:1002 acute AD model mice 984:1002 In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. 35588599 2 56 from protein 423:429 arg1 removal 361:367 the removal 357:367 the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein 357:429 O-GlcNAcylation of tau can negatively regulate hyperphosphorylation and the O-GlcNAcase (OGA) catalyzes the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein. 35588599 4 57 theme OGA 658:660 arg1 scaffold 672:679 a novel OGA inhibitor scaffold 650:679 a novel OGA inhibitor scaffold bearing three parts 650:699 Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. 36229208 4 0 theme Venous 760:765 arg1 blood 767:771 Venous blood 760:771 Venous blood from the medial canthus of the female mice 760:814 Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. 36229208 4 1 theme 21st 889:892 arg1 days 894:897 the 1st, 7th, 14th and 21st days 866:897 the 1st, 7th, 14th and 21st days 866:897 Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. 36229208 3 2 theme unpredictable 599:611 arg1 model 630:634 A chronic unpredictable mild stimulation model 589:634 A chronic unpredictable mild stimulation model during pregnancy 589:651 A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. 36229208 1 3 theme intestinal 398:407 arg1 tract 409:413 the intestinal tract 394:413 the intestinal tract 394:413 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 8 4 theme stress 1489:1494 arg1 group 1496:1500 the stress group 1485:1500 the stress group 1485:1500 In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . 36229208 1 5 theme intestinal 233:242 arg1 flora 244:248 the intestinal flora 229:248 the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress 229:331 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 7 6 theme female 1323:1328 arg1 mice 1330:1333 female mice 1323:1333 female mice 1323:1333 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 10 7 theme stress 1997:2002 arg1 group 2004:2008 the stress group 1993:2008 the stress group 1993:2008 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 12 8 theme stress 2487:2492 arg1 group 2504:2508 the stress offspring group 2483:2508 the stress offspring group 2483:2508 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 6 9 theme 20-day 1033:1038 arg1 mice 1060:1063 20-day postnatal offspring mice 1033:1063 20-day postnatal offspring mice 1033:1063 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 9 10 theme Lactobacillus 1670:1682 arg1 higher 1713:1718 higher 1713:1718 higher 1713:1718 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 9 10 theme Lactobacillus 1670:1682 arg1 proportions 1635:1645 the proportions 1631:1645 the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group 1631:1706 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 8 11 theme female 1455:1460 arg1 mice 1462:1465 female mice 1455:1465 female mice 1455:1465 In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . 36229208 6 12 theme alpha 1123:1127 arg1 diversity 1129:1137 alpha diversity 1123:1137 alpha diversity 1123:1137 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 12 13 from proportion 2636:2645 arg1 group 2692:2696 the stress+LBP offspring group 2667:2696 the stress+LBP offspring group 2667:2696 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 0 14 theme rats 90:93 arg1 flora 72:76 the intestinal flora 57:76 the intestinal flora of pregnant rats 57:93 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 9 15 theme Lachnospiraceae 1650:1664 arg1 higher 1713:1718 higher 1713:1718 higher 1713:1718 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 9 15 theme Lachnospiraceae 1650:1664 arg1 proportions 1635:1645 the proportions 1631:1645 the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group 1631:1706 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 9 16 theme flora 1581:1585 arg1 structure 1587:1595 intestinal flora structure 1570:1595 intestinal flora structure 1570:1595 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 7 17 theme plasma 1284:1289 arg1 concentration 1306:1318 the plasma corticosterone concentration 1280:1318 the plasma corticosterone concentration of female mice in the stress group and stress+LBP group 1280:1374 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 7 17 theme plasma 1284:1289 arg1 higher 1380:1385 higher 1380:1385 higher 1380:1385 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 12 18 theme stress+LBP 2430:2439 arg1 group 2451:2455 the stress+LBP offspring group 2426:2455 the stress+LBP offspring group 2426:2455 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 6 19 theme mice 1011:1014 arg1 feces 995:999 The fresh feces 985:999 The fresh feces of famale mice after stress and 20-day postnatal offspring mice 985:1063 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 6 20 theme Miseq 1094:1098 arg1 technology 1111:1120 Illumina Miseq sequencing technology 1085:1120 Illumina Miseq sequencing technology 1085:1120 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 4 21 theme female 804:809 arg1 mice 811:814 the female mice 800:814 the female mice 800:814 Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. 36229208 12 22 from Clostridiales 2650:2662 arg1 group 2692:2696 the stress+LBP offspring group 2667:2696 the stress+LBP offspring group 2667:2696 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 23 theme offspring 2347:2355 arg1 group 2357:2361 stress offspring group 2340:2361 stress offspring group 2340:2361 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 24 theme Bacteroidales 2529:2541 arg1 lower 2581:2585 lower 2581:2585 lower 2581:2585 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 24 theme Bacteroidales 2529:2541 arg1 proportion 2515:2524 the proportion 2511:2524 the proportion of Bacteroidales in the stress+LBP offspring group 2511:2575 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 8 25 theme control 1529:1535 arg1 P<0.05 1544:1549 P<0.05 1544:1549 P<0.05 1544:1549 In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . 36229208 8 25 theme control 1529:1535 arg1 group 1537:1541 the control group 1525:1541 the control group (P<0.05) 1525:1550 In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . 36229208 1 26 theme Lycium 189:194 arg1 LBP 221:223 LBP 221:223 LBP 221:223 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 1 26 theme Lycium 189:194 arg1 polysaccharide 205:218 Lycium barbarum polysaccharide 189:218 Lycium barbarum polysaccharide (LBP) 189:224 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 12 27 theme offspring 2745:2753 arg1 groups 2755:2760 the stress and control offspring groups 2722:2760 groups 2755:2760 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 6 28 theme Illumina 1085:1092 arg1 technology 1111:1120 Illumina Miseq sequencing technology 1085:1120 Illumina Miseq sequencing technology 1085:1120 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 3 29 theme 40 685:686 arg1 mg/kg 688:692 mg/kg 688:692 mg/kg 688:692 A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. 36229208 13 30 from changes 2815:2821 arg1 flora 2841:2845 the intestinal flora diversity, abundance and flora structure 2826:2886 the intestinal flora diversity, abundance and flora structure of mother mice 2826:2901 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 1 31 theme polysaccharide 205:218 arg1 effect 179:184 the improvement effect 163:184 the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress 163:331 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 4 32 theme medial 782:787 arg1 canthus 789:795 the medial canthus 778:795 the medial canthus of the female mice 778:814 Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. 36229208 13 33 theme mother 2891:2896 arg1 mice 2898:2901 mother mice 2891:2901 mother mice 2891:2901 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 11 34 theme stress+LBP 2127:2136 arg1 group 2148:2152 the stress+LBP offspring group 2123:2152 the stress+LBP offspring group 2123:2152 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 2 35 from rats 569:572 arg1 group 582:586 each group 577:586 each group 577:586 Methods: From July to October 2019, 24 SPF-grade female SD rats were selected and divided into control group, stress group, and stress+LBP group, with 8 rats in each group. 36229208 1 36 theme stress 384:389 arg1 effect 374:379 the effect 370:379 the effect of stress on the intestinal tract 370:413 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 2 37 theme control 511:517 arg1 group 519:523 control group 511:523 control group 511:523 Methods: From July to October 2019, 24 SPF-grade female SD rats were selected and divided into control group, stress group, and stress+LBP group, with 8 rats in each group. 36229208 12 38 theme stress 2340:2345 arg1 group 2357:2361 stress offspring group 2340:2361 stress offspring group 2340:2361 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 7 39 theme stress 1272:1277 arg1 days 1264:1267 the 7th and 14th days 1247:1267 the 7th and 14th days of stress 1247:1277 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 3 40 theme 8th 741:743 arg1 day 745:747 the 8th day 737:747 the 8th day of stress 737:757 A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. 36229208 11 41 theme offspring 2059:2067 arg1 group 2069:2073 the offspring group 2055:2073 the offspring group 2055:2073 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 6 42 theme offspring 1050:1058 arg1 mice 1060:1063 20-day postnatal offspring mice 1033:1063 20-day postnatal offspring mice 1033:1063 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 9 43 theme control 1755:1761 arg1 group 1763:1767 control group 1755:1767 control group 1755:1767 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 12 44 from group 2692:2696 arg1 proportion 2636:2645 the proportion 2632:2645 the proportion of Clostridiales in the stress+LBP offspring group 2632:2696 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 44 from group 2692:2696 arg1 higher 2702:2707 higher 2702:2707 higher 2702:2707 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 3 45 theme LBP 694:696 arg1 solution 698:705 40 mg/kg LBP solution 685:705 40 mg/kg LBP solution 685:705 A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. 36229208 0 46 theme intestinal 61:70 arg1 flora 72:76 the intestinal flora 57:76 the intestinal flora of pregnant rats 57:93 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 12 47 theme stress+LBP 2671:2680 arg1 group 2692:2696 the stress+LBP offspring group 2667:2696 the stress+LBP offspring group 2667:2696 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 48 theme offspring 2561:2569 arg1 group 2571:2575 the stress+LBP offspring group 2546:2575 the stress+LBP offspring group 2546:2575 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 11 49 theme group 2148:2152 arg1 index 2088:2092 the Shannon index 2076:2092 the Shannon index 2076:2092 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 11 49 theme group 2148:2152 arg1 index 2099:2103 Ace index 2095:2103 Ace index 2095:2103 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 11 49 theme group 2148:2152 arg1 index 2114:2118 Chao index 2109:2118 Chao index of the stress+LBP offspring group 2109:2152 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 11 49 theme group 2148:2152 arg1 higher 2159:2164 higher 2159:2164 higher 2159:2164 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 13 50 theme flora 2872:2876 arg1 structure 2878:2886 flora structure 2872:2886 flora structure 2872:2886 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 12 51 theme Lactobacillus 2236:2248 arg1 higher 2288:2293 higher 2288:2293 higher 2288:2293 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 51 theme Lactobacillus 2236:2248 arg1 proportion 2222:2231 The proportion 2218:2231 The proportion of Lactobacillus in the stress+LBP offspring group 2218:2282 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 10 52 theme Lactobacillales 1953:1967 arg1 proportion 1939:1948 the proportion 1935:1948 the proportion of Lactobacillales 1935:1967 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 10 52 theme Lactobacillales 1953:1967 arg1 higher 1973:1978 higher 1973:1978 higher 1973:1978 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 6 53 theme intestinal 1217:1226 arg1 flora 1228:1232 intestinal flora 1217:1232 intestinal flora 1217:1232 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 12 54 from Bacteroidales 2529:2541 arg1 group 2571:2575 the stress+LBP offspring group 2546:2575 the stress+LBP offspring group 2546:2575 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 2 55 theme female 465:470 arg1 rats 475:478 24 SPF-grade female SD rats 452:478 24 SPF-grade female SD rats 452:478 Methods: From July to October 2019, 24 SPF-grade female SD rats were selected and divided into control group, stress group, and stress+LBP group, with 8 rats in each group. 36229208 11 56 theme Shannon 2080:2086 arg1 index 2088:2092 the Shannon index 2076:2092 the Shannon index 2076:2092 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 11 56 theme Shannon 2080:2086 arg1 higher 2159:2164 higher 2159:2164 higher 2159:2164 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 1 57 theme new 346:348 arg1 ideas 350:354 new ideas 346:354 new ideas for improving the effect of stress on the intestinal tract 346:413 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 13 58 theme intestinal 2830:2839 arg1 flora 2841:2845 the intestinal flora diversity, abundance and flora structure 2826:2886 the intestinal flora diversity, abundance and flora structure of mother mice 2826:2901 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 9 59 theme intestinal 1570:1579 arg1 flora 1581:1585 intestinal flora 1570:1585 intestinal flora structure 1570:1595 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 11 60 theme offspring 2191:2199 arg1 P<0.05 2208:2213 P<0.05 2208:2213 P<0.05 2208:2213 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 11 60 theme offspring 2191:2199 arg1 group 2201:2205 the stress offspring group 2180:2205 the stress offspring group (P<0.05) 2180:2214 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 11 61 theme Chao 2109:2112 arg1 index 2114:2118 Chao index 2109:2118 Chao index of the stress+LBP offspring group 2109:2152 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 12 62 theme Clostridiales 2650:2662 arg1 proportion 2636:2645 the proportion 2632:2645 the proportion of Clostridiales in the stress+LBP offspring group 2632:2696 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 62 theme Clostridiales 2650:2662 arg1 higher 2702:2707 higher 2702:2707 higher 2702:2707 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 0 63 theme [Improvement 0:11 arg1 effect 13:18 [Improvement effect 0:18 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats 0:93 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 1 64 theme mother 253:258 arg1 mice 260:263 mother mice 253:263 mother mice 253:263 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 9 65 theme structure 1587:1595 arg1 analysis 1558:1565 The analysis 1554:1565 The analysis of intestinal flora structure 1554:1595 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 12 66 theme offspring 2268:2276 arg1 group 2278:2282 the stress+LBP offspring group 2253:2282 the stress+LBP offspring group 2253:2282 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 13 67 theme flora 2991:2995 arg1 balance 2969:2975 the balance 2965:2975 the balance of intestinal flora 2965:2995 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 7 68 theme stress+LBP 1359:1368 arg1 group 1370:1374 stress+LBP group 1359:1374 stress+LBP group 1359:1374 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 12 69 from proportion 2222:2231 arg1 group 2278:2282 the stress+LBP offspring group 2253:2282 the stress+LBP offspring group 2253:2282 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 10 70 theme stress+LBP 1829:1838 arg1 group 1840:1844 the stress+LBP group 1825:1844 the stress+LBP group 1825:1844 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 6 71 theme postnatal 1040:1048 arg1 mice 1060:1063 20-day postnatal offspring mice 1033:1063 20-day postnatal offspring mice 1033:1063 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 3 72 theme chronic 591:597 arg1 model 630:634 A chronic unpredictable mild stimulation model 589:634 A chronic unpredictable mild stimulation model during pregnancy 589:651 A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. 36229208 12 73 theme stress 2604:2609 arg1 group 2621:2625 the stress offspring group 2600:2625 the stress offspring group 2600:2625 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 8 74 theme mice 1462:1465 arg1 diversity 1442:1450 the Alpha diversity 1432:1450 the Alpha diversity of female mice 1432:1465 In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . 36229208 10 75 from proportion 1794:1803 arg1 group 1840:1844 the stress+LBP group 1825:1844 the stress+LBP group 1825:1844 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 13 76 from offspring 2907:2915 arg1 flora 2841:2845 the intestinal flora diversity, abundance and flora structure 2826:2886 the intestinal flora diversity, abundance and flora structure of mother mice 2826:2901 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 7 77 theme mice 1330:1333 arg1 concentration 1306:1318 the plasma corticosterone concentration 1280:1318 the plasma corticosterone concentration of female mice in the stress group and stress+LBP group 1280:1374 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 7 77 theme mice 1330:1333 arg1 higher 1380:1385 higher 1380:1385 higher 1380:1385 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 11 78 theme group 2069:2073 arg1 diversity 2042:2050 the Alpha diversity 2032:2050 the Alpha diversity of the offspring group 2032:2073 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 6 79 theme community 1143:1151 arg1 composition 1153:1163 community composition 1143:1163 community composition 1143:1163 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 12 80 from group 2571:2575 arg1 lower 2581:2585 lower 2581:2585 lower 2581:2585 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 80 from group 2571:2575 arg1 proportion 2515:2524 the proportion 2511:2524 the proportion of Bacteroidales in the stress+LBP offspring group 2511:2575 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 81 theme offspring 2441:2449 arg1 group 2451:2455 the stress+LBP offspring group 2426:2455 the stress+LBP offspring group 2426:2455 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 8 82 theme Alpha 1436:1440 arg1 diversity 1442:1450 the Alpha diversity 1432:1450 the Alpha diversity of female mice 1432:1465 In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . 36229208 3 83 theme mild 613:616 arg1 model 630:634 A chronic unpredictable mild stimulation model 589:634 A chronic unpredictable mild stimulation model during pregnancy 589:651 A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. 36229208 12 84 theme control 2737:2743 arg1 groups 2755:2760 the stress and control offspring groups 2722:2760 groups 2755:2760 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 85 theme control 2312:2318 arg1 group 2330:2334 the control offspring group 2308:2334 the control offspring group 2308:2334 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 7 86 theme corticosterone 1291:1304 arg1 concentration 1306:1318 the plasma corticosterone concentration 1280:1318 the plasma corticosterone concentration of female mice in the stress group and stress+LBP group 1280:1374 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 7 86 theme corticosterone 1291:1304 arg1 higher 1380:1385 higher 1380:1385 higher 1380:1385 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 2 87 theme stress 526:531 arg1 group 533:537 stress group 526:537 stress group 526:537 Methods: From July to October 2019, 24 SPF-grade female SD rats were selected and divided into control group, stress group, and stress+LBP group, with 8 rats in each group. 36229208 10 88 theme stress 1874:1879 arg1 group 1881:1885 the stress group 1870:1885 the stress group 1870:1885 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 8 89 theme group 1496:1500 arg1 lower 1506:1510 lower 1506:1510 lower 1506:1510 In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . 36229208 8 89 theme group 1496:1500 arg1 index 1476:1480 the Ace index 1468:1480 the Ace index of the stress group 1468:1500 In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . 36229208 4 90 theme 1st 870:872 arg1 days 894:897 the 1st, 7th, 14th and 21st days 866:897 the 1st, 7th, 14th and 21st days 866:897 Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. 36229208 12 91 theme Ruminococcaceae 2407:2421 arg1 proportions 2372:2382 the proportions 2368:2382 the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group 2368:2455 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 91 theme Ruminococcaceae 2407:2421 arg1 higher 2462:2467 higher 2462:2467 higher 2462:2467 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 9 92 theme stress+LBP 1691:1700 arg1 group 1702:1706 the stress+LBP group 1687:1706 the stress+LBP group 1687:1706 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 6 93 theme sequencing 1100:1109 arg1 technology 1111:1120 Illumina Miseq sequencing technology 1085:1120 Illumina Miseq sequencing technology 1085:1120 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 1 94 theme improvement 167:177 arg1 effect 179:184 the improvement effect 163:184 the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress 163:331 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 2 95 theme stress+LBP 544:553 arg1 group 555:559 stress+LBP group 544:559 stress+LBP group 544:559 Methods: From July to October 2019, 24 SPF-grade female SD rats were selected and divided into control group, stress group, and stress+LBP group, with 8 rats in each group. 36229208 7 96 theme 14th 1259:1262 arg1 days 1264:1267 the 7th and 14th days 1247:1267 the 7th and 14th days of stress 1247:1277 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 0 97 theme chronic 121:127 arg1 stress 129:134 chronic stress 121:134 chronic stress 121:134 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 6 98 theme famale 1004:1009 arg1 mice 1011:1014 famale mice 1004:1014 famale mice after stress 1004:1027 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 6 99 used used 1170:1173 arg2 composition 1153:1163 community composition 1143:1163 community composition 1143:1163 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 6 99 used used 1170:1173 arg2 diversity 1129:1137 alpha diversity 1123:1137 alpha diversity 1123:1137 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 6 99 used used 1170:1173 arg2 technology 1111:1120 Illumina Miseq sequencing technology 1085:1120 Illumina Miseq sequencing technology 1085:1120 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 7 100 theme 7th 1251:1253 arg1 days 1264:1267 the 7th and 14th days 1247:1267 the 7th and 14th days of stress 1247:1277 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 13 101 dep flora 2841:2845 arg1 abundance 2858:2866 abundance 2858:2866 abundance 2858:2866 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 13 101 dep flora 2841:2845 arg1 structure 2878:2886 flora structure 2872:2886 flora structure 2872:2886 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 13 101 dep flora 2841:2845 arg1 diversity 2847:2855 diversity 2847:2855 diversity 2847:2855 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 4 102 theme mice 811:814 arg1 canthus 789:795 the medial canthus 778:795 the medial canthus of the female mice 778:814 Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. 36229208 10 103 theme control 1914:1920 arg1 group 1922:1926 the control group 1910:1926 the control group 1910:1926 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 3 104 theme mg/kg 688:692 arg1 solution 698:705 40 mg/kg LBP solution 685:705 40 mg/kg LBP solution 685:705 A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. 36229208 6 105 dep diversity 1190:1198 arg1 the 1186:1188 the 1186:1188 the 1186:1188 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 0 106 from offspring 105:113 arg1 flora 72:76 the intestinal flora 57:76 the intestinal flora of pregnant rats 57:93 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 13 107 theme mice 2898:2901 arg1 flora 2841:2845 the intestinal flora diversity, abundance and flora structure 2826:2886 the intestinal flora diversity, abundance and flora structure of mother mice 2826:2901 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 9 108 theme stress 1738:1743 arg1 group 1745:1749 the stress group 1734:1749 the stress group 1734:1749 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 4 109 from canthus 789:795 arg1 blood 767:771 Venous blood 760:771 Venous blood from the medial canthus of the female mice 760:814 Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. 36229208 3 110 theme stress 752:757 arg1 day 745:747 the 8th day 737:747 the 8th day of stress 737:757 A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. 36229208 6 111 theme mice 1060:1063 arg1 feces 995:999 The fresh feces 985:999 The fresh feces of famale mice after stress and 20-day postnatal offspring mice 985:1063 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 10 112 theme order 1777:1781 arg1 level 1783:1787 the order level 1773:1787 the order level 1773:1787 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 12 113 theme offspring 2682:2690 arg1 group 2692:2696 the stress+LBP offspring group 2667:2696 the stress+LBP offspring group 2667:2696 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 1 114 from effect 179:184 arg1 flora 244:248 the intestinal flora 229:248 the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress 229:331 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 7 115 theme control 1404:1410 arg1 group 1412:1416 the control group 1400:1416 the control group (P<0.05) 1400:1425 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 7 115 theme control 1404:1410 arg1 P<0.05 1419:1424 P<0.05 1419:1424 P<0.05 1419:1424 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 7 116 from concentration 1306:1318 arg1 group 1349:1353 the stress group 1338:1353 the stress group 1338:1353 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 7 116 from concentration 1306:1318 arg1 group 1370:1374 stress+LBP group 1359:1374 stress+LBP group 1359:1374 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 11 117 theme offspring 2138:2146 arg1 group 2148:2152 the stress+LBP offspring group 2123:2152 the stress+LBP offspring group 2123:2152 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 1 118 from effect 374:379 arg1 tract 409:413 the intestinal tract 394:413 the intestinal tract 394:413 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 0 119 theme pregnant 81:88 arg1 rats 90:93 pregnant rats 81:93 pregnant rats 81:93 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 1 120 theme chronic 318:324 arg1 stress 326:331 chronic stress 318:331 chronic stress 318:331 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 12 121 theme stress+LBP 2550:2559 arg1 group 2571:2575 the stress+LBP offspring group 2546:2575 the stress+LBP offspring group 2546:2575 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 0 122 from effect 13:18 arg1 flora 72:76 the intestinal flora 57:76 the intestinal flora of pregnant rats 57:93 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 12 123 theme offspring 2320:2328 arg1 group 2330:2334 the control offspring group 2308:2334 the control offspring group 2308:2334 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 6 124 theme flora 1228:1232 arg1 structure 1204:1212 structure 1204:1212 structure 1204:1212 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 6 124 theme flora 1228:1232 arg1 diversity 1190:1198 diversity 1190:1198 diversity 1190:1198 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 2 125 theme SD 472:473 arg1 rats 475:478 24 SPF-grade female SD rats 452:478 24 SPF-grade female SD rats 452:478 Methods: From July to October 2019, 24 SPF-grade female SD rats were selected and divided into control group, stress group, and stress+LBP group, with 8 rats in each group. 36229208 10 126 from Clostridiales 1808:1820 arg1 group 1840:1844 the stress+LBP group 1825:1844 the stress+LBP group 1825:1844 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 5 127 theme corticosterone 940:953 arg1 concentration 955:967 corticosterone concentration 940:967 corticosterone concentration 940:967 Cortisol was measured and corticosterone concentration was calculated. 36229208 12 128 theme Lachnospiraceae 2387:2401 arg1 proportions 2372:2382 the proportions 2368:2382 the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group 2368:2455 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 12 128 theme Lachnospiraceae 2387:2401 arg1 higher 2462:2467 higher 2462:2467 higher 2462:2467 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 2 129 theme SPF-grade 455:463 arg1 rats 475:478 24 SPF-grade female SD rats 452:478 24 SPF-grade female SD rats 452:478 Methods: From July to October 2019, 24 SPF-grade female SD rats were selected and divided into control group, stress group, and stress+LBP group, with 8 rats in each group. 36229208 11 130 theme stress 2184:2189 arg1 P<0.05 2208:2213 P<0.05 2208:2213 P<0.05 2208:2213 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 11 130 theme stress 2184:2189 arg1 group 2201:2205 the stress offspring group 2180:2205 the stress offspring group (P<0.05) 2180:2214 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 12 131 theme stress+LBP 2257:2266 arg1 group 2278:2282 the stress+LBP offspring group 2253:2282 the stress+LBP offspring group 2253:2282 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 4 132 theme 1st 837:839 arg1 day 841:843 the 1st day 833:843 the 1st day before stress 833:857 Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. 36229208 4 133 theme 7th 875:877 arg1 days 894:897 the 1st, 7th, 14th and 21st days 866:897 the 1st, 7th, 14th and 21st days 866:897 Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. 36229208 13 134 theme pregnancy 2927:2935 arg1 stress 2937:2942 pregnancy stress 2927:2942 pregnancy stress 2927:2942 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 11 135 theme Ace 2095:2097 arg1 index 2099:2103 Ace index 2095:2103 Ace index 2095:2103 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 10 136 from group 1840:1844 arg1 higher 1850:1855 higher 1850:1855 higher 1850:1855 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 10 136 from group 1840:1844 arg1 proportion 1794:1803 the proportion 1790:1803 the proportion of Clostridiales in the stress+LBP group 1790:1844 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 0 137 theme Lycium 23:28 arg1 polysaccharide 39:52 Lycium barbarum polysaccharide 23:52 Lycium barbarum polysaccharide 23:52 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 1 138 theme mice 260:263 arg1 flora 244:248 the intestinal flora 229:248 the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress 229:331 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 13 139 theme intestinal 2980:2989 arg1 flora 2991:2995 intestinal flora 2980:2995 intestinal flora 2980:2995 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 4 140 theme 14th 880:883 arg1 days 894:897 the 1st, 7th, 14th and 21st days 866:897 the 1st, 7th, 14th and 21st days 866:897 Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. 36229208 12 141 theme offspring 2611:2619 arg1 group 2621:2625 the stress offspring group 2600:2625 the stress offspring group 2600:2625 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 0 142 theme polysaccharide 39:52 arg1 effect 13:18 [Improvement effect 0:18 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats 0:93 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 0 142 theme polysaccharide 39:52 arg1 offspring 105:113 their offspring 99:113 their offspring under chronic stress 99:134 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 12 143 from proportions 2372:2382 arg1 group 2451:2455 the stress+LBP offspring group 2426:2455 the stress+LBP offspring group 2426:2455 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 11 144 theme Alpha 2036:2040 arg1 diversity 2042:2050 the Alpha diversity 2032:2050 the Alpha diversity of the offspring group 2032:2073 In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . 36229208 9 145 from proportions 1635:1645 arg1 group 1702:1706 the stress+LBP group 1687:1706 the stress+LBP group 1687:1706 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 12 146 from proportion 2515:2524 arg1 group 2571:2575 the stress+LBP offspring group 2546:2575 the stress+LBP offspring group 2546:2575 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 36229208 6 147 theme fresh 989:993 arg1 feces 995:999 The fresh feces 985:999 The fresh feces of famale mice after stress and 20-day postnatal offspring mice 985:1063 The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. 36229208 9 148 theme species 1616:1622 arg1 level 1624:1628 the species level 1612:1628 the species level 1612:1628 The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. 36229208 3 149 dep established 657:667 arg1 days 673:676 21 days 670:676 21 days 670:676 A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. 36229208 0 150 dep Lycium 23:28 arg1 barbarum 30:37 barbarum 30:37 barbarum 30:37 [Improvement effect of Lycium barbarum polysaccharide on the intestinal flora of pregnant rats and their offspring under chronic stress]. 36229208 13 151 theme LBP 2795:2797 arg1 intervention 2779:2790 The intervention 2775:2790 The intervention of LBP 2775:2797 Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora. 36229208 10 152 theme control 2014:2020 arg1 group 2022:2026 control group 2014:2026 control group 2014:2026 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 8 153 theme Ace 1472:1474 arg1 lower 1506:1510 lower 1506:1510 lower 1506:1510 In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . 36229208 8 153 theme Ace 1472:1474 arg1 index 1476:1480 the Ace index 1468:1480 the Ace index of the stress group 1468:1500 In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . 36229208 7 154 theme stress 1342:1347 arg1 group 1349:1353 the stress group 1338:1353 the stress group 1338:1353 Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . 36229208 10 155 theme Clostridiales 1808:1820 arg1 higher 1850:1855 higher 1850:1855 higher 1850:1855 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 10 155 theme Clostridiales 1808:1820 arg1 proportion 1794:1803 the proportion 1790:1803 the proportion of Clostridiales in the stress+LBP group 1790:1844 At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. 36229208 3 156 theme stimulation 618:628 arg1 model 630:634 A chronic unpredictable mild stimulation model 589:634 A chronic unpredictable mild stimulation model during pregnancy 589:651 A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. 36229208 1 157 dep Lycium 189:194 arg1 barbarum 196:203 barbarum 196:203 barbarum 196:203 Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. 36229208 12 158 theme offspring 2494:2502 arg1 group 2504:2508 the stress offspring group 2483:2508 the stress offspring group 2483:2508 The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. 37212203 4 0 theme mono-ligated 501:512 arg1 complexes 514:522 The mono-ligated complexes 497:522 The mono-ligated complexes 497:522 The mono-ligated complexes present an aryloxy-bridged dimeric structure, which is retained in solution in the case of Zn complexes but not with aluminum according to DOSY NMR experiments. 37212203 7 1 from complexes 1027:1035 arg1 cases 983:987 both cases 978:987 both cases 978:987 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 7 2 theme Zn 1024:1025 arg1 catalysts 1010:1018 the most performant catalysts 990:1018 the most performant catalysts 990:1018 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 7 2 theme Zn 1024:1025 arg1 complexes 1027:1035 Zn complexes 1024:1035 Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm 1024:1114 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 1 3 link ortho-N-linked 175:188 arg1 amidine 205:211 an ortho-N-linked trisubstituted amidine 172:211 an ortho-N-linked trisubstituted amidine 172:211 We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine. 37212203 4 4 theme DOSY 663:666 arg1 experiments 672:682 DOSY NMR experiments 663:682 DOSY NMR experiments 663:682 The mono-ligated complexes present an aryloxy-bridged dimeric structure, which is retained in solution in the case of Zn complexes but not with aluminum according to DOSY NMR experiments. 37212203 7 5 theme dimethylamino 1098:1110 arg1 arm 1112:1114 a pendant additional dimethylamino arm 1077:1114 a pendant additional dimethylamino arm 1077:1114 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 5 6 theme fluxional 726:734 arg1 behaviour 736:744 fluxional behaviour 726:744 fluxional behaviour 726:744 Bis(ligated) Al and Zn complexes exhibit fluxional behaviour in solution attributed to coordination-decoordination of the amidine moiety and the rotation around the amidine C-NR'2 and C-Ar bonds. 37212203 2 7 theme metal/ligand 343:354 arg1 ratio 356:360 the metal/ligand ratio 339:360 the metal/ligand ratio used 339:365 The reaction of the phenol-amidine proligands with aluminum and zinc alkyls gave mono- or bis-ligated complexes depending on the metal/ligand ratio used. 37212203 3 8 theme X-Ray 469:473 arg1 analysis 487:494 X-Ray diffraction analysis 469:494 X-Ray diffraction analysis 469:494 The solid-state structure of four proligands and thirteen Zn and Al complexes has been determined by X-Ray diffraction analysis. 37212203 2 9 theme zinc 278:281 arg1 alkyls 283:288 zinc alkyls 278:288 zinc alkyls 278:288 The reaction of the phenol-amidine proligands with aluminum and zinc alkyls gave mono- or bis-ligated complexes depending on the metal/ligand ratio used. 37212203 1 10 theme aryloxy 146:152 arg1 moiety 154:159 an aryloxy moiety 143:159 an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine 143:211 We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine. 37212203 5 11 theme amidine 807:813 arg1 moiety 815:820 the amidine moiety 803:820 the amidine moiety 803:820 Bis(ligated) Al and Zn complexes exhibit fluxional behaviour in solution attributed to coordination-decoordination of the amidine moiety and the rotation around the amidine C-NR'2 and C-Ar bonds. 37212203 7 12 theme pendant 1079:1085 arg1 arm 1112:1114 a pendant additional dimethylamino arm 1077:1114 a pendant additional dimethylamino arm 1077:1114 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 5 13 theme moiety 815:820 arg1 coordination-decoordination 772:798 coordination-decoordination 772:798 coordination-decoordination of the amidine moiety 772:820 Bis(ligated) Al and Zn complexes exhibit fluxional behaviour in solution attributed to coordination-decoordination of the amidine moiety and the rotation around the amidine C-NR'2 and C-Ar bonds. 37212203 5 13 theme moiety 815:820 arg1 rotation 830:837 the rotation 826:837 the rotation around the amidine C-NR'2 and C-Ar bonds 826:878 Bis(ligated) Al and Zn complexes exhibit fluxional behaviour in solution attributed to coordination-decoordination of the amidine moiety and the rotation around the amidine C-NR'2 and C-Ar bonds. 37212203 6 14 theme bulk 958:961 arg1 conditions 963:972 bulk conditions 958:972 bulk conditions 958:972 These complexes were tested for the ROP of rac-lactide in solution and under bulk conditions. 37212203 6 15 from ROP 917:919 arg1 solution 939:946 solution 939:946 solution 939:946 These complexes were tested for the ROP of rac-lactide in solution and under bulk conditions. 37212203 2 16 with reaction 218:225 arg1 alkyls 283:288 zinc alkyls 278:288 zinc alkyls 278:288 The reaction of the phenol-amidine proligands with aluminum and zinc alkyls gave mono- or bis-ligated complexes depending on the metal/ligand ratio used. 37212203 2 16 with reaction 218:225 arg1 aluminum 265:272 aluminum 265:272 aluminum 265:272 The reaction of the phenol-amidine proligands with aluminum and zinc alkyls gave mono- or bis-ligated complexes depending on the metal/ligand ratio used. 37212203 2 17 theme bis-ligated 304:314 arg1 complexes 316:324 mono- or bis-ligated complexes 295:324 mono- or bis-ligated complexes 295:324 The reaction of the phenol-amidine proligands with aluminum and zinc alkyls gave mono- or bis-ligated complexes depending on the metal/ligand ratio used. 37212203 3 18 theme Al 433:434 arg1 complexes 436:444 thirteen Zn and Al complexes 417:444 thirteen Zn and Al complexes 417:444 The solid-state structure of four proligands and thirteen Zn and Al complexes has been determined by X-Ray diffraction analysis. 37212203 3 19 theme solid-state 372:382 arg1 structure 384:392 The solid-state structure 368:392 The solid-state structure of four proligands and thirteen Zn and Al complexes 368:444 The solid-state structure of four proligands and thirteen Zn and Al complexes has been determined by X-Ray diffraction analysis. 37212203 1 20 theme ortho-N-linked 175:188 arg1 amidine 205:211 an ortho-N-linked trisubstituted amidine 172:211 an ortho-N-linked trisubstituted amidine 172:211 We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine. 37212203 0 21 theme Zn 7:8 arg1 phenoxy-amidine 10:24 Zn phenoxy-amidine 7:24 Zn phenoxy-amidine 7:24 Al and Zn phenoxy-amidine complexes for lactide ROP catalysis. 37212203 7 22 theme phenoxy-amidine 1049:1063 arg1 ligand 1065:1070 a phenoxy-amidine ligand 1047:1070 a phenoxy-amidine ligand with a pendant additional dimethylamino arm 1047:1114 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 2 23 theme mono- 295:299 arg1 complexes 316:324 mono- or bis-ligated complexes 295:324 mono- or bis-ligated complexes 295:324 The reaction of the phenol-amidine proligands with aluminum and zinc alkyls gave mono- or bis-ligated complexes depending on the metal/ligand ratio used. 37212203 1 24 theme trisubstituted 190:203 arg1 amidine 205:211 an ortho-N-linked trisubstituted amidine 172:211 an ortho-N-linked trisubstituted amidine 172:211 We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine. 37212203 1 25 contain possessing 161:170 arg2 amidine 205:211 an ortho-N-linked trisubstituted amidine 172:211 an ortho-N-linked trisubstituted amidine 172:211 We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine. 37212203 1 25 contain possessing 161:170 arg1 moiety 154:159 an aryloxy moiety 143:159 an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine 143:211 We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine. 37212203 4 26 theme NMR 668:670 arg1 experiments 672:682 DOSY NMR experiments 663:682 DOSY NMR experiments 663:682 The mono-ligated complexes present an aryloxy-bridged dimeric structure, which is retained in solution in the case of Zn complexes but not with aluminum according to DOSY NMR experiments. 37212203 5 27 theme amidine 850:856 arg1 C-NR 858:861 the amidine C-NR'2 846:863 the amidine C-NR'2 846:863 Bis(ligated) Al and Zn complexes exhibit fluxional behaviour in solution attributed to coordination-decoordination of the amidine moiety and the rotation around the amidine C-NR'2 and C-Ar bonds. 37212203 3 28 theme Zn 426:427 arg1 complexes 436:444 thirteen Zn and Al complexes 417:444 thirteen Zn and Al complexes 417:444 The solid-state structure of four proligands and thirteen Zn and Al complexes has been determined by X-Ray diffraction analysis. 37212203 4 29 theme dimeric 551:557 arg1 structure 559:567 an aryloxy-bridged dimeric structure 532:567 an aryloxy-bridged dimeric structure 532:567 The mono-ligated complexes present an aryloxy-bridged dimeric structure, which is retained in solution in the case of Zn complexes but not with aluminum according to DOSY NMR experiments. 37212203 5 30 theme Zn 705:706 arg1 complexes 708:716 Bis(ligated) Al and Zn complexes 685:716 Bis(ligated) Al and Zn complexes 685:716 Bis(ligated) Al and Zn complexes exhibit fluxional behaviour in solution attributed to coordination-decoordination of the amidine moiety and the rotation around the amidine C-NR'2 and C-Ar bonds. 37212203 5 31 dep Bis 685:687 arg1 ligated 689:695 ligated 689:695 ligated 689:695 Bis(ligated) Al and Zn complexes exhibit fluxional behaviour in solution attributed to coordination-decoordination of the amidine moiety and the rotation around the amidine C-NR'2 and C-Ar bonds. 37212203 0 32 theme ROP 48:50 arg1 catalysis 52:60 lactide ROP catalysis 40:60 lactide ROP catalysis 40:60 Al and Zn phenoxy-amidine complexes for lactide ROP catalysis. 37212203 4 33 theme aryloxy-bridged 535:549 arg1 structure 559:567 an aryloxy-bridged dimeric structure 532:567 an aryloxy-bridged dimeric structure 532:567 The mono-ligated complexes present an aryloxy-bridged dimeric structure, which is retained in solution in the case of Zn complexes but not with aluminum according to DOSY NMR experiments. 37212203 3 34 theme complexes 436:444 arg1 structure 384:392 The solid-state structure 368:392 The solid-state structure of four proligands and thirteen Zn and Al complexes 368:444 The solid-state structure of four proligands and thirteen Zn and Al complexes has been determined by X-Ray diffraction analysis. 37212203 7 35 theme most 994:997 arg1 catalysts 1010:1018 the most performant catalysts 990:1018 the most performant catalysts 990:1018 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 7 35 theme most 994:997 arg1 complexes 1027:1035 Zn complexes 1024:1035 Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm 1024:1114 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 1 36 theme new 92:94 arg1 generation 96:105 a new generation 90:105 a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine 90:211 We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine. 37212203 0 37 theme lactide 40:46 arg1 catalysis 52:60 lactide ROP catalysis 40:60 lactide ROP catalysis 40:60 Al and Zn phenoxy-amidine complexes for lactide ROP catalysis. 37212203 5 38 theme Bis 685:687 arg1 complexes 708:716 Bis(ligated) Al and Zn complexes 685:716 Bis(ligated) Al and Zn complexes 685:716 Bis(ligated) Al and Zn complexes exhibit fluxional behaviour in solution attributed to coordination-decoordination of the amidine moiety and the rotation around the amidine C-NR'2 and C-Ar bonds. 37212203 1 39 theme generation 96:105 arg1 synthesis 77:85 the synthesis 73:85 the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine 73:211 We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine. 37212203 7 40 theme performant 999:1008 arg1 catalysts 1010:1018 the most performant catalysts 990:1018 the most performant catalysts 990:1018 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 7 40 theme performant 999:1008 arg1 complexes 1027:1035 Zn complexes 1024:1035 Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm 1024:1114 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 3 41 theme diffraction 475:485 arg1 analysis 487:494 X-Ray diffraction analysis 469:494 X-Ray diffraction analysis 469:494 The solid-state structure of four proligands and thirteen Zn and Al complexes has been determined by X-Ray diffraction analysis. 37212203 5 42 theme C-Ar 869:872 arg1 bonds 874:878 C-Ar bonds 869:878 C-Ar bonds 869:878 Bis(ligated) Al and Zn complexes exhibit fluxional behaviour in solution attributed to coordination-decoordination of the amidine moiety and the rotation around the amidine C-NR'2 and C-Ar bonds. 37212203 4 43 theme Zn 615:616 arg1 complexes 618:626 Zn complexes 615:626 Zn complexes 615:626 The mono-ligated complexes present an aryloxy-bridged dimeric structure, which is retained in solution in the case of Zn complexes but not with aluminum according to DOSY NMR experiments. 37212203 7 44 theme additional 1087:1096 arg1 arm 1112:1114 a pendant additional dimethylamino arm 1077:1114 a pendant additional dimethylamino arm 1077:1114 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 1 45 theme phenoxy-amidine 110:124 arg1 ligands 126:132 phenoxy-amidine ligands 110:132 phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine 110:211 We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine. 37212203 7 46 with ligand 1065:1070 arg1 arm 1112:1114 a pendant additional dimethylamino arm 1077:1114 a pendant additional dimethylamino arm 1077:1114 In both cases, the most performant catalysts are Zn complexes featuring a phenoxy-amidine ligand with a pendant additional dimethylamino arm. 37212203 2 47 theme proligands 249:258 arg1 reaction 218:225 The reaction 214:225 The reaction of the phenol-amidine proligands with aluminum and zinc alkyls 214:288 The reaction of the phenol-amidine proligands with aluminum and zinc alkyls gave mono- or bis-ligated complexes depending on the metal/ligand ratio used. 37212203 1 48 theme ligands 126:132 arg1 generation 96:105 a new generation 90:105 a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine 90:211 We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an ortho-N-linked trisubstituted amidine. 37212203 3 49 theme proligands 402:411 arg1 structure 384:392 The solid-state structure 368:392 The solid-state structure of four proligands and thirteen Zn and Al complexes 368:444 The solid-state structure of four proligands and thirteen Zn and Al complexes has been determined by X-Ray diffraction analysis. 37212203 2 50 theme phenol-amidine 234:247 arg1 proligands 249:258 the phenol-amidine proligands 230:258 the phenol-amidine proligands 230:258 The reaction of the phenol-amidine proligands with aluminum and zinc alkyls gave mono- or bis-ligated complexes depending on the metal/ligand ratio used. 37212203 6 51 theme rac-lactide 924:934 arg1 ROP 917:919 the ROP 913:919 the ROP of rac-lactide in solution and under bulk conditions 913:972 These complexes were tested for the ROP of rac-lactide in solution and under bulk conditions. 37212203 4 52 theme complexes 618:626 arg1 case 607:610 the case 603:610 the case of Zn complexes 603:626 The mono-ligated complexes present an aryloxy-bridged dimeric structure, which is retained in solution in the case of Zn complexes but not with aluminum according to DOSY NMR experiments. 35865361 1 0 theme immune 169:174 arg1 responses 176:184 aberrant immune responses 160:184 aberrant immune responses 160:184 Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. 35865361 7 1 theme host 1112:1115 arg1 importance 1088:1097 the importance 1084:1097 the importance of including host and viral carbohydrate antigens 1084:1147 Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. 35865361 5 2 theme antiglycan 652:661 arg1 signals 667:673 nearly all antiglycan IgM signals 641:673 nearly all antiglycan IgM signals 641:673 Additionally, nearly all antiglycan IgM signals were lower in COVID-19 patients, indicating a global dysregulation of this class of antibodies. 35865361 5 3 theme IgM 663:665 arg1 signals 667:673 nearly all antiglycan IgM signals 641:673 nearly all antiglycan IgM signals 641:673 Additionally, nearly all antiglycan IgM signals were lower in COVID-19 patients, indicating a global dysregulation of this class of antibodies. 35865361 1 4 theme immune 79:84 arg1 system 86:91 Our immune system 75:91 Our immune system 75:91 Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. 35865361 3 5 theme carbohydrate 349:360 arg1 microarray 370:379 a carbohydrate antigen microarray 347:379 a carbohydrate antigen microarray 347:379 Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. 35865361 4 6 theme COVID-19 488:495 arg1 patients 497:504 COVID-19 patients 488:504 COVID-19 patients 488:504 COVID-19 patients had numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders. 35865361 3 7 theme antigen 362:368 arg1 microarray 370:379 a carbohydrate antigen microarray 347:379 a carbohydrate antigen microarray 347:379 Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. 35865361 4 8 theme numerous 510:517 arg1 autoantibodies 519:532 numerous autoantibodies 510:532 numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders 510:624 COVID-19 patients had numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders. 35865361 0 9 theme SARS-CoV-2-infected 45:63 arg1 patients 65:72 SARS-CoV-2-infected patients 45:72 SARS-CoV-2-infected patients 45:72 Abnormal antibodies to self-carbohydrates in SARS-CoV-2-infected patients. 35865361 2 10 theme clinical 288:295 arg1 outcome 297:303 the clinical outcome 284:303 the clinical outcome 284:303 While antibodies to glycans could recognize the virus and influence the clinical outcome, little is known about their roles. 35865361 3 11 theme serum 394:398 arg1 antibodies 400:409 serum antibodies 394:409 serum antibodies 394:409 Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. 35865361 1 12 theme deleterious 195:205 arg1 effects 207:213 deleterious effects 195:213 deleterious effects 195:213 Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. 35865361 0 13 theme Abnormal 0:7 arg1 antibodies 9:18 Abnormal antibodies 0:18 Abnormal antibodies to self-carbohydrates in SARS-CoV-2-infected patients 0:72 Abnormal antibodies to self-carbohydrates in SARS-CoV-2-infected patients. 35865361 5 14 theme COVID-19 689:696 arg1 patients 698:705 COVID-19 patients 689:705 COVID-19 patients 689:705 Additionally, nearly all antiglycan IgM signals were lower in COVID-19 patients, indicating a global dysregulation of this class of antibodies. 35865361 5 15 theme class 750:754 arg1 dysregulation 728:740 a global dysregulation 719:740 a global dysregulation of this class of antibodies 719:768 Additionally, nearly all antiglycan IgM signals were lower in COVID-19 patients, indicating a global dysregulation of this class of antibodies. 35865361 6 16 theme severe 835:840 arg1 disease 842:848 more severe disease 830:848 more severe disease 830:848 Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. 35865361 6 17 dep did 854:856 arg1 as 851:852 as 851:852 as 851:852 Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. 35865361 7 18 theme patients 1059:1066 arg1 analysis 1038:1045 clinical analysis 1029:1045 clinical analysis of COVID-19 patients 1029:1066 Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. 35865361 7 19 theme viral 1121:1125 arg1 antigens 1140:1147 including host and viral carbohydrate antigens 1102:1147 antigens 1140:1147 Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. 35865361 6 20 theme low 858:860 arg1 levels 862:867 low levels 858:867 low levels of antibodies to the Forssman antigen and ovalbumin 858:919 Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. 35865361 3 21 theme control 422:428 arg1 subjects 430:437 healthy control subjects 414:437 healthy control subjects 414:437 Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. 35865361 4 22 theme neurological 603:614 arg1 disorders 616:624 neurological disorders 603:624 neurological disorders 603:624 COVID-19 patients had numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders. 35865361 5 23 theme antibodies 759:768 arg1 class 750:754 this class 745:754 this class of antibodies 745:768 Additionally, nearly all antiglycan IgM signals were lower in COVID-19 patients, indicating a global dysregulation of this class of antibodies. 35865361 4 24 theme antiganglioside 561:575 arg1 antibodies 577:586 antiganglioside antibodies 561:586 antiganglioside antibodies that can cause neurological disorders 561:624 COVID-19 patients had numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders. 35865361 7 25 theme carbohydrate 1127:1138 arg1 antigens 1140:1147 including host and viral carbohydrate antigens 1102:1147 antigens 1140:1147 Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. 35865361 1 26 contain have 190:193 arg2 effects 207:213 deleterious effects 195:213 deleterious effects 195:213 Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. 35865361 1 26 contain have 190:193 arg1 responses 176:184 aberrant immune responses 160:184 aberrant immune responses 160:184 Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. 35865361 3 27 theme separate 470:477 arg1 cohorts 479:485 two separate cohorts 466:485 two separate cohorts 466:485 Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. 35865361 6 28 link N-linked 797:804 arg1 glycans 806:812 certain N-linked glycans 789:812 certain N-linked glycans 789:812 Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. 35865361 5 29 theme global 721:726 arg1 dysregulation 728:740 a global dysregulation 719:740 a global dysregulation of this class of antibodies 719:768 Additionally, nearly all antiglycan IgM signals were lower in COVID-19 patients, indicating a global dysregulation of this class of antibodies. 35865361 4 30 contain had 506:508 arg1 patients 497:504 COVID-19 patients 488:504 COVID-19 patients 488:504 COVID-19 patients had numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders. 35865361 4 30 contain had 506:508 arg2 autoantibodies 519:532 numerous autoantibodies 510:532 numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders 510:624 COVID-19 patients had numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders. 35865361 3 31 theme healthy 414:420 arg1 subjects 430:437 healthy control subjects 414:437 healthy control subjects 414:437 Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. 35865361 7 32 theme antigens 1140:1147 arg1 importance 1088:1097 the importance 1084:1097 the importance of including host and viral carbohydrate antigens 1084:1147 Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. 35865361 6 33 theme Forssman 890:897 arg1 antigen 899:905 the Forssman antigen 886:905 the Forssman antigen 886:905 Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. 35865361 3 34 from cohorts 479:485 arg1 patients 452:459 COVID-19 patients 443:459 COVID-19 patients from two separate cohorts 443:485 Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. 35865361 3 34 from cohorts 479:485 arg1 subjects 430:437 healthy control subjects 414:437 healthy control subjects 414:437 Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. 35865361 1 35 theme SARS-CoV-2 133:142 arg1 infections 144:153 SARS-CoV-2 infections 133:153 SARS-CoV-2 infections 133:153 Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. 35865361 7 36 theme expanded 962:969 arg1 testing 971:977 expanded testing 962:977 expanded testing for antiglycan antibodies 962:1003 Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. 35865361 7 37 theme antiglycan 983:992 arg1 antibodies 994:1003 antiglycan antibodies 983:1003 antiglycan antibodies 983:1003 Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. 35865361 7 38 theme clinical 1029:1036 arg1 analysis 1038:1045 clinical analysis 1029:1045 clinical analysis of COVID-19 patients 1029:1066 Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. 35865361 7 39 theme including 1102:1110 arg1 host 1112:1115 including host and viral carbohydrate antigens 1102:1147 host 1112:1115 Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. 35865361 6 40 theme N-linked 797:804 arg1 glycans 806:812 certain N-linked glycans 789:812 certain N-linked glycans 789:812 Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. 35865361 7 41 theme immune 1163:1168 arg1 responses 1170:1178 immune responses 1163:1178 immune responses to viruses 1163:1189 Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. 35865361 6 42 theme antibodies 872:881 arg1 levels 862:867 low levels 858:867 low levels of antibodies to the Forssman antigen and ovalbumin 858:919 Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. 35865361 6 43 theme certain 789:795 arg1 glycans 806:812 certain N-linked glycans 789:812 certain N-linked glycans 789:812 Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. 35865361 0 44 from self-carbohydrates 23:40 arg1 patients 65:72 SARS-CoV-2-infected patients 45:72 SARS-CoV-2-infected patients 45:72 Abnormal antibodies to self-carbohydrates in SARS-CoV-2-infected patients. 35865361 1 45 theme aberrant 160:167 arg1 responses 176:184 aberrant immune responses 160:184 aberrant immune responses 160:184 Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. 35341933 12 0 theme ginseng 2353:2359 arg1 mechanism 2334:2342 the mechanism 2330:2342 the mechanism of Panax ginseng on QDLC 2330:2367 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 10 1 theme bacteria 1665:1672 arg1 species 1654:1660 25 species 1651:1660 25 species of bacteria with significant differences of effective parts on QDLC 1651:1728 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 10 1 theme bacteria 1665:1672 arg1 species 1737:1743 23 species 1734:1743 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides 1734:1842 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 1 2 theme liver 242:246 arg1 research 255:262 liver cancer research 242:262 liver cancer research in traditional Chinese medicine (TCM) 242:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 10 3 theme parts 1716:1720 arg1 differences 1691:1701 significant differences 1679:1701 significant differences of effective parts on QDLC 1679:1728 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 4 4 from ginseng 608:614 arg1 treatment 623:631 the treatment 619:631 the treatment of QDLC 619:639 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 1 5 theme research 255:262 arg1 part 234:237 an important part 221:237 an important part of liver cancer research in traditional Chinese medicine (TCM) 221:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 5 theme research 255:262 arg1 cancer 204:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer 153:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) 153:216 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 11 6 theme potential 2114:2122 arg1 relationship 2124:2135 the close potential relationship 2104:2135 the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds 2104:2239 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 1 7 from medicine 287:294 arg1 part 234:237 an important part 221:237 an important part of liver cancer research in traditional Chinese medicine (TCM) 221:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 7 from medicine 287:294 arg1 cancer 204:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer 153:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) 153:216 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 0 8 theme Comprehensive 0:12 arg1 metabolomics 20:31 Comprehensive fecal metabolomics 0:31 Comprehensive fecal metabolomics 0:31 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 1 9 theme Qi 184:185 arg1 part 234:237 an important part 221:237 an important part of liver cancer research in traditional Chinese medicine (TCM) 221:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 9 theme Qi 184:185 arg1 QDLC 212:215 QDLC 212:215 QDLC 212:215 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 9 theme Qi 184:185 arg1 cancer 204:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer 153:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) 153:216 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 0 10 theme liver 139:143 arg1 cancer 145:150 Qi-deficiency liver cancer 125:150 Qi-deficiency liver cancer 125:150 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 8 11 theme pharmacodynamic 1205:1219 arg1 biomarkers 1231:1240 31 pharmacodynamic potential biomarkers 1202:1240 31 pharmacodynamic potential biomarkers 1202:1240 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 2 12 contain has 421:423 arg2 ginseng 341:347 Panax ginseng 335:347 Panax ginseng 335:347 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 12 contain has 421:423 arg1 function 412:419 its function 408:419 its function 408:419 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 12 contain has 421:423 arg2 medicine 394:401 the main Chinese herbal medicine 370:401 the main Chinese herbal medicine 370:401 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 12 contain has 421:423 arg2 significance 433:444 special significance 425:444 special significance 425:444 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 1 13 theme liver 198:202 arg1 part 234:237 an important part 221:237 an important part of liver cancer research in traditional Chinese medicine (TCM) 221:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 13 theme liver 198:202 arg1 QDLC 212:215 QDLC 212:215 QDLC 212:215 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 13 theme liver 198:202 arg1 cancer 204:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer 153:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) 153:216 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 9 14 theme metabolic 1396:1404 arg1 pathways 1406:1413 6 major metabolic pathways 1388:1413 6 major metabolic pathways 1388:1413 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 1 15 from research 255:262 arg1 TCM 297:299 TCM 297:299 TCM 297:299 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 15 from research 255:262 arg1 medicine 287:294 traditional Chinese medicine 267:294 traditional Chinese medicine (TCM) 267:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 4 16 theme QDLC 636:639 arg1 treatment 623:631 the treatment 619:631 the treatment of QDLC 619:639 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 11 17 theme potential 1934:1942 arg1 relationship 1944:1955 a complex potential relationship 1924:1955 a complex potential relationship among phenotype, gut microbiota and fecal metabolites 1924:2009 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 5 18 theme metabolic 794:802 arg1 pathways 804:811 related metabolic pathways 786:811 related metabolic pathways 786:811 MATERIALS AND METHODS Firstly, biomarkers and related metabolic pathways were screened and identified by metabonomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. 35341933 8 19 theme potential 1261:1269 arg1 biomarkers 1271:1280 20 synergistic potential biomarkers 1246:1280 20 synergistic potential biomarkers 1246:1280 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 1 20 from part 234:237 arg1 TCM 297:299 TCM 297:299 TCM 297:299 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 20 from part 234:237 arg1 medicine 287:294 traditional Chinese medicine 267:294 traditional Chinese medicine (TCM) 267:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 12 21 theme metabolites 2293:2303 arg1 changes 2265:2271 the changes 2261:2271 the changes of fecal endogenous metabolites and intestinal bacteria 2261:2327 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 11 22 theme ginseng 2052:2058 arg1 intervention 2060:2071 Panax ginseng intervention 2046:2071 Panax ginseng intervention 2046:2071 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 0 23 from Ginseng 97:103 arg1 treatment 112:120 the treatment 108:120 the treatment of Qi-deficiency liver cancer 108:150 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 9 24 theme pyrimidine 1553:1562 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 24 theme pyrimidine 1553:1562 arg1 metabolism 1564:1573 pyrimidine metabolism 1553:1573 pyrimidine metabolism 1553:1573 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 10 25 theme synergistic 1789:1799 arg1 action 1801:1806 synergistic action 1789:1806 synergistic action of ginsenosides and polysaccharides 1789:1842 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 5 26 theme Genes 884:888 arg1 metabonomics 845:856 metabonomics 845:856 metabonomics 845:856 MATERIALS AND METHODS Firstly, biomarkers and related metabolic pathways were screened and identified by metabonomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. 35341933 2 27 theme tumor 453:457 arg1 treatment 459:467 the tumor treatment 449:467 the tumor treatment of Qi deficiency constitution 449:497 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 12 28 theme intestinal 2309:2318 arg1 bacteria 2320:2327 intestinal bacteria 2309:2327 intestinal bacteria 2309:2327 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 8 29 theme parts 1295:1299 arg1 biomarkers 1271:1280 20 synergistic potential biomarkers 1246:1280 20 synergistic potential biomarkers 1246:1280 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 8 29 theme parts 1295:1299 arg1 biomarkers 1231:1240 31 pharmacodynamic potential biomarkers 1202:1240 31 pharmacodynamic potential biomarkers 1202:1240 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 12 30 dep CONCLUSION 2242:2251 arg1 changes 2265:2271 the changes 2261:2271 the changes of fecal endogenous metabolites and intestinal bacteria 2261:2327 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 8 31 theme Panax 1304:1308 arg1 ginseng 1310:1316 Panax ginseng 1304:1316 Panax ginseng on QDLC 1304:1324 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 7 32 theme spearman 1160:1167 arg1 coefficient 1181:1191 spearman correlation coefficient 1160:1191 spearman correlation coefficient 1160:1191 Finally, the relationship among phenotypes, gut microbiota and fecal metabolites was comprehensively analyzed by spearman correlation coefficient. 35341933 1 33 theme ETHNOPHARMACOLOGICAL 153:172 arg1 part 234:237 an important part 221:237 an important part of liver cancer research in traditional Chinese medicine (TCM) 221:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 33 theme ETHNOPHARMACOLOGICAL 153:172 arg1 QDLC 212:215 QDLC 212:215 QDLC 212:215 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 33 theme ETHNOPHARMACOLOGICAL 153:172 arg1 cancer 204:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer 153:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) 153:216 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 6 34 theme rRNA 929:932 arg1 technique 945:953 16S rRNA sequencing technique 925:953 16S rRNA sequencing technique 925:953 Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. 35341933 2 35 theme deficiency 475:484 arg1 constitution 486:497 Qi deficiency constitution 472:497 Qi deficiency constitution 472:497 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 12 36 theme fecal 2276:2280 arg1 metabolites 2293:2303 fecal endogenous metabolites 2276:2303 fecal endogenous metabolites 2276:2303 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 11 37 theme fecal 1993:1997 arg1 metabolites 1999:2009 fecal metabolites 1993:2009 fecal metabolites 1993:2009 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 5 38 theme database 909:916 arg1 metabonomics 845:856 metabonomics 845:856 metabonomics 845:856 MATERIALS AND METHODS Firstly, biomarkers and related metabolic pathways were screened and identified by metabonomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. 35341933 9 39 theme fatty 1476:1480 arg1 biosynthesis 1487:1498 unsaturated fatty acid biosynthesis 1464:1498 unsaturated fatty acid biosynthesis 1464:1498 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 39 theme fatty 1476:1480 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 10 40 theme genus 1638:1642 arg1 level 1644:1648 the genus level 1634:1648 the genus level 1634:1648 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 4 41 theme previous 703:710 arg1 evaluation 728:737 previous pharmacodynamic evaluation 703:737 previous pharmacodynamic evaluation 703:737 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 11 42 theme Spearman 1872:1879 arg1 analysis 1893:1900 Spearman correlation analysis 1872:1900 Spearman correlation analysis 1872:1900 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 0 43 theme Ginseng 97:103 arg1 mechanism 78:86 the mechanism 74:86 the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer 74:150 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 9 44 theme acid 1536:1539 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 44 theme acid 1536:1539 arg1 metabolism 1541:1550 arachidonic acid metabolism 1524:1550 arachidonic acid metabolism 1524:1550 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 11 45 theme unsaturated 2196:2206 arg1 acids 2214:2218 unsaturated fatty acids 2196:2218 unsaturated fatty acids 2196:2218 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 4 46 theme gut 672:674 arg1 microbiota 676:685 gut microbiota 672:685 gut microbiota 672:685 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 10 47 theme gut 1615:1617 arg1 microbiota 1619:1628 gut microbiota 1615:1628 gut microbiota 1615:1628 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 7 48 theme fecal 1110:1114 arg1 metabolites 1116:1126 fecal metabolites 1110:1126 fecal metabolites 1110:1126 Finally, the relationship among phenotypes, gut microbiota and fecal metabolites was comprehensively analyzed by spearman correlation coefficient. 35341933 8 49 from parts 1295:1299 arg1 QDLC 1321:1324 QDLC 1321:1324 QDLC 1321:1324 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 5 50 theme Genomes 894:900 arg1 database 909:916 Genomes (KEGG) database 894:916 Genomes (KEGG) database 894:916 MATERIALS AND METHODS Firstly, biomarkers and related metabolic pathways were screened and identified by metabonomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. 35341933 6 51 theme β 996:996 arg1 diversity 998:1006 β diversity 996:1006 β diversity 996:1006 Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. 35341933 2 52 theme Chinese 379:385 arg1 significance 433:444 special significance 425:444 special significance 425:444 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 52 theme Chinese 379:385 arg1 ginseng 341:347 Panax ginseng 335:347 Panax ginseng 335:347 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 52 theme Chinese 379:385 arg1 medicine 394:401 the main Chinese herbal medicine 370:401 the main Chinese herbal medicine 370:401 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 1 53 theme Chinese 279:285 arg1 TCM 297:299 TCM 297:299 TCM 297:299 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 53 theme Chinese 279:285 arg1 medicine 287:294 traditional Chinese medicine 267:294 traditional Chinese medicine (TCM) 267:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 11 54 theme gut 1974:1976 arg1 microbiota 1978:1987 gut microbiota 1974:1987 gut microbiota 1974:1987 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 9 55 theme major 1390:1394 arg1 pathways 1406:1413 6 major metabolic pathways 1388:1413 6 major metabolic pathways 1388:1413 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 2 56 theme special 425:431 arg1 significance 433:444 special significance 425:444 special significance 425:444 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 56 theme special 425:431 arg1 ginseng 341:347 Panax ginseng 335:347 Panax ginseng 335:347 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 56 theme special 425:431 arg1 medicine 394:401 the main Chinese herbal medicine 370:401 the main Chinese herbal medicine 370:401 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 0 57 theme gut 37:39 arg1 microbiota 41:50 gut microbiota 37:50 gut microbiota 37:50 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 9 58 theme vitamin 1576:1582 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 58 theme vitamin 1576:1582 arg1 metabolism 1587:1596 vitamin B6 metabolism 1576:1596 vitamin B6 metabolism 1576:1596 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 8 59 from QDLC 1321:1324 arg1 parts 1295:1299 effective parts 1285:1299 effective parts of Panax ginseng on QDLC 1285:1324 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 4 60 theme research 558:565 arg1 AIM 537:539 AIM 537:539 AIM OF THE STUDY The research 537:565 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 2 61 theme Panax 335:339 arg1 significance 433:444 special significance 425:444 special significance 425:444 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 61 theme Panax 335:339 arg1 ginseng 341:347 Panax ginseng 335:347 Panax ginseng 335:347 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 61 theme Panax 335:339 arg1 medicine 394:401 the main Chinese herbal medicine 370:401 the main Chinese herbal medicine 370:401 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 8 62 from ginseng 1310:1316 arg1 QDLC 1321:1324 QDLC 1321:1324 QDLC 1321:1324 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 1 63 theme important 224:232 arg1 part 234:237 an important part 221:237 an important part of liver cancer research in traditional Chinese medicine (TCM) 221:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 63 theme important 224:232 arg1 cancer 204:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer 153:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) 153:216 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 6 64 theme gut 1031:1033 arg1 microbiota 1035:1044 gut microbiota 1031:1044 gut microbiota 1031:1044 Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. 35341933 4 65 theme The 554:556 arg1 research 558:565 THE STUDY The research 544:565 THE STUDY The research 544:565 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 2 66 theme treatment 324:332 arg1 course 310:315 the course 306:315 the course of its treatment 306:332 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 4 67 from treatment 623:631 arg1 mechanism 589:597 the mechanism 585:597 the mechanism of Panax ginseng in the treatment of QDLC 585:639 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 12 68 from ginseng 2353:2359 arg1 QDLC 2364:2367 QDLC 2364:2367 QDLC 2364:2367 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 12 69 theme Panax 2347:2351 arg1 ginseng 2353:2359 Panax ginseng 2347:2359 Panax ginseng on QDLC 2347:2367 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 1 70 theme cancer 248:253 arg1 research 255:262 liver cancer research 242:262 liver cancer research in traditional Chinese medicine (TCM) 242:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 12 71 from QDLC 2364:2367 arg1 mechanism 2334:2342 the mechanism 2330:2342 the mechanism of Panax ginseng on QDLC 2330:2367 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 10 72 theme effective 1706:1714 arg1 parts 1716:1720 effective parts 1706:1720 effective parts on QDLC 1706:1728 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 4 73 theme ginseng 608:614 arg1 mechanism 589:597 the mechanism 585:597 the mechanism of Panax ginseng in the treatment of QDLC 585:639 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 1 74 theme RELEVANCE 174:182 arg1 part 234:237 an important part 221:237 an important part of liver cancer research in traditional Chinese medicine (TCM) 221:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 74 theme RELEVANCE 174:182 arg1 QDLC 212:215 QDLC 212:215 QDLC 212:215 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 74 theme RELEVANCE 174:182 arg1 cancer 204:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer 153:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) 153:216 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 5 75 dep MATERIALS 740:748 arg1 identified 831:840 identified 831:840 identified by metabonomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) database 831:916 MATERIALS AND METHODS Firstly, biomarkers and related metabolic pathways were screened and identified by metabonomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. 35341933 5 75 dep MATERIALS 740:748 arg1 screened 818:825 screened 818:825 screened 818:825 MATERIALS AND METHODS Firstly, biomarkers and related metabolic pathways were screened and identified by metabonomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. 35341933 6 76 used used 959:962 arg2 technique 945:953 16S rRNA sequencing technique 925:953 16S rRNA sequencing technique 925:953 Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. 35341933 4 77 from mechanism 589:597 arg1 treatment 623:631 the treatment 619:631 the treatment of QDLC 619:639 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 4 78 dep evaluation 728:737 arg1 basis 694:698 basis 694:698 basis 694:698 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 4 78 dep evaluation 728:737 arg1 the 690:692 the 690:692 the 690:692 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 10 79 with bacteria 1748:1755 arg1 differences 1774:1784 significant differences 1762:1784 significant differences of synergistic action of ginsenosides and polysaccharides 1762:1842 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 11 80 theme close 2108:2112 arg1 relationship 2124:2135 the close potential relationship 2104:2135 the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds 2104:2239 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 10 81 from differences 1691:1701 arg1 QDLC 1725:1728 QDLC 1725:1728 QDLC 1725:1728 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 4 82 theme Panax 602:606 arg1 ginseng 608:614 Panax ginseng 602:614 Panax ginseng in the treatment of QDLC 602:639 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 1 83 theme deficiency 187:196 arg1 part 234:237 an important part 221:237 an important part of liver cancer research in traditional Chinese medicine (TCM) 221:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 83 theme deficiency 187:196 arg1 QDLC 212:215 QDLC 212:215 QDLC 212:215 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 83 theme deficiency 187:196 arg1 cancer 204:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer 153:209 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) 153:216 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 11 84 theme Panax 2046:2050 arg1 intervention 2060:2071 Panax ginseng intervention 2046:2071 Panax ginseng intervention 2046:2071 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 0 85 from mechanism 78:86 arg1 treatment 112:120 the treatment 108:120 the treatment of Qi-deficiency liver cancer 108:150 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 9 86 theme tryptophan 1501:1510 arg1 metabolism 1512:1521 tryptophan metabolism 1501:1521 tryptophan metabolism 1501:1521 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 86 theme tryptophan 1501:1510 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 8 87 theme potential 1221:1229 arg1 biomarkers 1231:1240 31 pharmacodynamic potential biomarkers 1202:1240 31 pharmacodynamic potential biomarkers 1202:1240 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 0 88 theme Qi-deficiency 125:137 arg1 cancer 145:150 Qi-deficiency liver cancer 125:150 Qi-deficiency liver cancer 125:150 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 10 89 theme significant 1762:1772 arg1 differences 1774:1784 significant differences 1762:1784 significant differences of synergistic action of ginsenosides and polysaccharides 1762:1842 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 5 90 theme related 786:792 arg1 pathways 804:811 related metabolic pathways 786:811 related metabolic pathways 786:811 MATERIALS AND METHODS Firstly, biomarkers and related metabolic pathways were screened and identified by metabonomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. 35341933 2 91 theme constitution 486:497 arg1 treatment 459:467 the tumor treatment 449:467 the tumor treatment of Qi deficiency constitution 449:497 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 11 92 theme indole 2224:2229 arg1 compounds 2231:2239 indole compounds 2224:2239 indole compounds 2224:2239 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 0 93 theme cancer 145:150 arg1 treatment 112:120 the treatment 108:120 the treatment of Qi-deficiency liver cancer 108:150 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 10 94 theme bacteria 1748:1755 arg1 species 1654:1660 25 species 1651:1660 25 species of bacteria with significant differences of effective parts on QDLC 1651:1728 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 10 94 theme bacteria 1748:1755 arg1 species 1737:1743 23 species 1734:1743 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides 1734:1842 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 8 95 theme synergistic 1249:1259 arg1 biomarkers 1271:1280 20 synergistic potential biomarkers 1246:1280 20 synergistic potential biomarkers 1246:1280 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 10 96 theme action 1801:1806 arg1 differences 1774:1784 significant differences 1762:1784 significant differences of synergistic action of ginsenosides and polysaccharides 1762:1842 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 9 97 theme unsaturated 1464:1474 arg1 biosynthesis 1487:1498 unsaturated fatty acid biosynthesis 1464:1498 unsaturated fatty acid biosynthesis 1464:1498 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 97 theme unsaturated 1464:1474 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 11 98 theme intervention 2060:2071 arg1 development 2022:2032 the development 2018:2032 the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds 2018:2239 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 12 99 theme bacteria 2320:2327 arg1 changes 2265:2271 the changes 2261:2271 the changes of fecal endogenous metabolites and intestinal bacteria 2261:2327 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 4 100 theme fecal 649:653 arg1 metabonomics 655:666 fecal metabonomics 649:666 fecal metabonomics 649:666 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 7 101 theme correlation 1169:1179 arg1 coefficient 1181:1191 spearman correlation coefficient 1160:1191 spearman correlation coefficient 1160:1191 Finally, the relationship among phenotypes, gut microbiota and fecal metabolites was comprehensively analyzed by spearman correlation coefficient. 35341933 9 102 theme acid 1482:1485 arg1 biosynthesis 1487:1498 unsaturated fatty acid biosynthesis 1464:1498 unsaturated fatty acid biosynthesis 1464:1498 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 102 theme acid 1482:1485 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 10 103 from parts 1716:1720 arg1 QDLC 1725:1728 QDLC 1725:1728 QDLC 1725:1728 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 11 104 theme fatty 2208:2212 arg1 acids 2214:2218 unsaturated fatty acids 2196:2218 unsaturated fatty acids 2196:2218 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 8 105 theme effective 1285:1293 arg1 parts 1295:1299 effective parts 1285:1299 effective parts of Panax ginseng on QDLC 1285:1324 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 0 106 theme mechanism 78:86 arg1 evaluation 60:69 the evaluation 56:69 the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer 56:150 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 10 107 from QDLC 1725:1728 arg1 differences 1691:1701 significant differences 1679:1701 significant differences of effective parts on QDLC 1679:1728 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 6 108 theme sequencing 934:943 arg1 technique 945:953 16S rRNA sequencing technique 925:953 16S rRNA sequencing technique 925:953 Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. 35341933 12 109 theme endogenous 2282:2291 arg1 metabolites 2293:2303 fecal endogenous metabolites 2276:2303 fecal endogenous metabolites 2276:2303 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 12 110 from mechanism 2334:2342 arg1 QDLC 2364:2367 QDLC 2364:2367 QDLC 2364:2367 CONCLUSION Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified. 35341933 0 111 theme Panax 91:95 arg1 Ginseng 97:103 Panax Ginseng 91:103 Panax Ginseng in the treatment of Qi-deficiency liver cancer 91:150 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 6 112 theme 16S 925:927 arg1 rRNA 929:932 16S rRNA 925:932 16S rRNA sequencing technique 925:953 Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. 35341933 2 113 theme Qi 472:473 arg1 constitution 486:497 Qi deficiency constitution 472:497 Qi deficiency constitution 472:497 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 8 114 theme ginseng 1310:1316 arg1 parts 1295:1299 effective parts 1285:1299 effective parts of Panax ginseng on QDLC 1285:1324 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 9 115 theme arachidonic 1524:1534 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 115 theme arachidonic 1524:1534 arg1 metabolism 1541:1550 arachidonic acid metabolism 1524:1550 arachidonic acid metabolism 1524:1550 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 6 116 theme key 1012:1014 arg1 differences 1016:1026 key differences 1012:1026 key differences 1012:1026 Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. 35341933 10 117 theme microbiota 1619:1628 arg1 study 1606:1610 the study 1602:1610 the study of gut microbiota 1602:1628 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 0 118 theme fecal 14:18 arg1 metabolomics 20:31 Comprehensive fecal metabolomics 0:31 Comprehensive fecal metabolomics 0:31 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 11 119 theme fecal 2158:2162 arg1 acids 2189:2193 bile acids 2184:2193 bile acids 2184:2193 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 11 119 theme fecal 2158:2162 arg1 acids 2214:2218 unsaturated fatty acids 2196:2218 unsaturated fatty acids 2196:2218 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 11 119 theme fecal 2158:2162 arg1 metabolites 2164:2174 fecal metabolites 2158:2174 fecal metabolites 2158:2174 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 11 119 theme fecal 2158:2162 arg1 compounds 2231:2239 indole compounds 2224:2239 indole compounds 2224:2239 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 7 120 theme gut 1091:1093 arg1 microbiota 1095:1104 gut microbiota 1091:1104 gut microbiota 1091:1104 Finally, the relationship among phenotypes, gut microbiota and fecal metabolites was comprehensively analyzed by spearman correlation coefficient. 35341933 1 121 theme traditional 267:277 arg1 TCM 297:299 TCM 297:299 TCM 297:299 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 1 121 theme traditional 267:277 arg1 medicine 287:294 traditional Chinese medicine 267:294 traditional Chinese medicine (TCM) 267:300 ETHNOPHARMACOLOGICAL RELEVANCE Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). 35341933 8 122 dep RESULTS 1194:1200 arg1 identified 1344:1353 identified 1344:1353 identified by fecal metabonomics 1344:1375 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 8 122 dep RESULTS 1194:1200 arg1 screened 1331:1338 screened 1331:1338 screened 1331:1338 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 11 123 theme complex 1926:1932 arg1 relationship 1944:1955 a complex potential relationship 1924:1955 a complex potential relationship among phenotype, gut microbiota and fecal metabolites 1924:2009 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 2 124 theme herbal 387:392 arg1 significance 433:444 special significance 425:444 special significance 425:444 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 124 theme herbal 387:392 arg1 ginseng 341:347 Panax ginseng 335:347 Panax ginseng 335:347 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 124 theme herbal 387:392 arg1 medicine 394:401 the main Chinese herbal medicine 370:401 the main Chinese herbal medicine 370:401 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 10 125 theme polysaccharides 1828:1842 arg1 action 1801:1806 synergistic action 1789:1806 synergistic action of ginsenosides and polysaccharides 1789:1842 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 2 126 theme main 374:377 arg1 significance 433:444 special significance 425:444 special significance 425:444 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 126 theme main 374:377 arg1 ginseng 341:347 Panax ginseng 335:347 Panax ginseng 335:347 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 2 126 theme main 374:377 arg1 medicine 394:401 the main Chinese herbal medicine 370:401 the main Chinese herbal medicine 370:401 In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. 35341933 9 127 theme bile 1440:1443 arg1 biosynthesis 1487:1498 unsaturated fatty acid biosynthesis 1464:1498 unsaturated fatty acid biosynthesis 1464:1498 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 127 theme bile 1440:1443 arg1 metabolism 1587:1596 vitamin B6 metabolism 1576:1596 vitamin B6 metabolism 1576:1596 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 127 theme bile 1440:1443 arg1 metabolism 1541:1550 arachidonic acid metabolism 1524:1550 arachidonic acid metabolism 1524:1550 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 127 theme bile 1440:1443 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 127 theme bile 1440:1443 arg1 metabolism 1564:1573 pyrimidine metabolism 1553:1573 pyrimidine metabolism 1553:1573 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 127 theme bile 1440:1443 arg1 metabolism 1512:1521 tryptophan metabolism 1501:1521 tryptophan metabolism 1501:1521 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 11 128 theme bile 2184:2187 arg1 acids 2189:2193 bile acids 2184:2193 bile acids 2184:2193 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 10 129 theme ginsenosides 1811:1822 arg1 action 1801:1806 synergistic action 1789:1806 synergistic action of ginsenosides and polysaccharides 1789:1842 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 8 130 theme fecal 1358:1362 arg1 metabonomics 1364:1375 fecal metabonomics 1358:1375 fecal metabonomics 1358:1375 RESULTS 31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. 35341933 9 131 theme B6 1584:1585 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 131 theme B6 1584:1585 arg1 metabolism 1587:1596 vitamin B6 metabolism 1576:1596 vitamin B6 metabolism 1576:1596 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 11 132 theme QDLC 2037:2040 arg1 development 2022:2032 the development 2018:2032 the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds 2018:2239 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 10 133 with bacteria 1665:1672 arg1 differences 1691:1701 significant differences 1679:1701 significant differences of effective parts on QDLC 1679:1728 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 35341933 4 134 theme STUDY 548:552 arg1 research 558:565 THE STUDY The research 544:565 THE STUDY The research 544:565 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 4 135 theme pharmacodynamic 712:726 arg1 evaluation 728:737 previous pharmacodynamic evaluation 703:737 previous pharmacodynamic evaluation 703:737 AIM OF THE STUDY The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation. 35341933 9 136 theme acid 1445:1448 arg1 biosynthesis 1487:1498 unsaturated fatty acid biosynthesis 1464:1498 unsaturated fatty acid biosynthesis 1464:1498 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 136 theme acid 1445:1448 arg1 metabolism 1587:1596 vitamin B6 metabolism 1576:1596 vitamin B6 metabolism 1576:1596 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 136 theme acid 1445:1448 arg1 metabolism 1541:1550 arachidonic acid metabolism 1524:1550 arachidonic acid metabolism 1524:1550 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 136 theme acid 1445:1448 arg1 biosynthesis 1450:1461 bile acid biosynthesis 1440:1461 bile acid biosynthesis 1440:1461 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 136 theme acid 1445:1448 arg1 metabolism 1564:1573 pyrimidine metabolism 1553:1573 pyrimidine metabolism 1553:1573 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 9 136 theme acid 1445:1448 arg1 metabolism 1512:1521 tryptophan metabolism 1501:1521 tryptophan metabolism 1501:1521 And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. 35341933 6 137 theme microbiota 1035:1044 arg1 composition 983:993 the composition 979:993 the composition 979:993 Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. 35341933 6 137 theme microbiota 1035:1044 arg1 diversity 998:1006 β diversity 996:1006 β diversity 996:1006 Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. 35341933 6 137 theme microbiota 1035:1044 arg1 differences 1016:1026 key differences 1012:1026 key differences 1012:1026 Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. 35341933 11 138 theme correlation 1881:1891 arg1 analysis 1893:1900 Spearman correlation analysis 1872:1900 Spearman correlation analysis 1872:1900 In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds. 35341933 0 139 from treatment 112:120 arg1 mechanism 78:86 the mechanism 74:86 the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer 74:150 Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer. 35341933 10 140 theme significant 1679:1689 arg1 differences 1691:1701 significant differences 1679:1701 significant differences of effective parts on QDLC 1679:1728 In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. 34989826 6 0 theme intestine 1012:1020 arg1 state 999:1003 a normal physiological state 976:1003 a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups 976:1099 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 1 1 theme fatty 254:258 arg1 acids 260:264 fatty acids 254:264 fatty acids 254:264 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 6 2 theme salina 1079:1084 arg1 groups 1094:1099 salina dietary groups 1079:1099 salina dietary groups 1079:1099 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 11 3 theme diet 1702:1705 arg1 groups 1707:1712 all tested microalgae diet groups 1680:1712 all tested microalgae diet groups 1680:1712 Conversely, harmful bacteria Mycoplasma reduced in all tested microalgae diet groups. 34989826 6 4 theme expression 903:912 arg1 level 914:918 the gene expression level 894:918 the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β 894:971 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 11 5 theme tested 1684:1689 arg1 groups 1707:1712 all tested microalgae diet groups 1680:1712 all tested microalgae diet groups 1680:1712 Conversely, harmful bacteria Mycoplasma reduced in all tested microalgae diet groups. 34989826 15 6 theme fish 2059:2062 arg1 health 2064:2069 fish health 2059:2069 fish health 2059:2069 • Microalgae diets modulated the gut microbiota composition to improve fish health. 34989826 3 7 theme growth 577:582 arg1 performance 584:594 growth performance 577:594 growth performance 577:594 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 4 8 theme microalgae 697:706 arg1 diets 708:712 these five microalgae diets 686:712 these five microalgae diets 686:712 The results showed that these five microalgae diets could improve the feed conversion rate (FCR), especially the D. salina (FCR = 1.02%) and Schizochytrium sp. 34989826 11 9 theme harmful 1641:1647 arg1 bacteria 1649:1656 harmful bacteria 1641:1656 harmful bacteria 1641:1656 Conversely, harmful bacteria Mycoplasma reduced in all tested microalgae diet groups. 34989826 8 10 theme fish 1371:1374 arg1 microbiota 1357:1366 the gut microbiota 1349:1366 the gut microbiota of fish 1349:1374 We also found that microalgae diets could regulate the gut microbiota of fish as well as increase the relative abundance of probiotics. 34989826 7 11 theme marker 1131:1136 arg1 b7r 1138:1140 neutrophil marker b7r 1120:1140 neutrophil marker b7r 1120:1140 The expression of neutrophil marker b7r was increased in the C. sorokiniana diet group; after, the zebrafish were challenged with Vibrio anguillarum, improving the ability to resist this disease. 34989826 1 12 from abundant 157:164 arg1 habitats 177:184 various habitats 169:184 various habitats around the globe 169:201 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 5 13 theme additive 836:843 arg1 groups 845:850 (FCR = 1.20%) additive groups 822:850 (FCR = 1.20%) additive groups. 822:851 (FCR = 1.20%) additive groups. 34989826 6 14 theme pro-inflammatory 927:942 arg1 cytokines 944:952 the pro-inflammatory cytokines 923:952 the pro-inflammatory cytokines IL6, IL8, and IL1β 923:971 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 6 14 theme pro-inflammatory 927:942 arg1 IL8 959:961 IL8 959:961 IL8 959:961 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 6 14 theme pro-inflammatory 927:942 arg1 IL1β 968:971 IL1β 968:971 IL1β 968:971 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 6 14 theme pro-inflammatory 927:942 arg1 IL6 954:956 IL6 954:956 IL6 954:956 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 4 15 theme conversion 737:746 arg1 FCR 754:756 FCR 754:756 FCR 754:756 The results showed that these five microalgae diets could improve the feed conversion rate (FCR), especially the D. salina (FCR = 1.02%) and Schizochytrium sp. 34989826 4 15 theme conversion 737:746 arg1 rate 748:751 the feed conversion rate 728:751 the feed conversion rate (FCR) 728:757 The results showed that these five microalgae diets could improve the feed conversion rate (FCR), especially the D. salina (FCR = 1.02%) and Schizochytrium sp. 34989826 14 16 theme • 1906:1906 arg1 diets 1919:1923 • Microalgae diets 1906:1923 • Microalgae diets 1906:1923 • Microalgae diets attenuated the intestinal inflammatory responses of zebrafish. 34989826 8 17 theme relative 1400:1407 arg1 abundance 1409:1417 the relative abundance 1396:1417 the relative abundance of probiotics 1396:1431 We also found that microalgae diets could regulate the gut microbiota of fish as well as increase the relative abundance of probiotics. 34989826 0 18 theme gut 114:116 arg1 microbiota 118:127 gut microbiota 114:127 gut microbiota 114:127 Dietary supplementation with microalgae enhances the zebrafish growth performance by modulating immune status and gut microbiota. 34989826 12 19 theme source 1779:1784 arg1 microalgae 1746:1755 these microalgae 1740:1755 these microalgae 1740:1755 Our study indicated that these microalgae could serve as a food source supplement and benefit the health of fish. 34989826 12 19 theme source 1779:1784 arg1 health 1813:1818 the health 1809:1818 the health of fish 1809:1826 Our study indicated that these microalgae could serve as a food source supplement and benefit the health of fish. 34989826 12 19 theme source 1779:1784 arg1 supplement 1786:1795 a food source supplement 1772:1795 a food source supplement 1772:1795 Our study indicated that these microalgae could serve as a food source supplement and benefit the health of fish. 34989826 7 20 theme Vibrio 1232:1237 arg1 anguillarum 1239:1249 Vibrio anguillarum 1232:1249 Vibrio anguillarum 1232:1249 The expression of neutrophil marker b7r was increased in the C. sorokiniana diet group; after, the zebrafish were challenged with Vibrio anguillarum, improving the ability to resist this disease. 34989826 10 21 dep group 1597:1601 arg1 groups 1621:1626 the other groups 1611:1626 the other groups 1611:1626 additive group than in the other groups. 34989826 2 22 theme primitive 353:361 arg1 source 368:373 the basic and primitive food source 339:373 the basic and primitive food source of aquatic animals 339:392 Microalgae can be exploited as the basic and primitive food source of aquatic animals. 34989826 2 22 theme primitive 353:361 arg1 Microalgae 308:317 Microalgae 308:317 Microalgae 308:317 Microalgae can be exploited as the basic and primitive food source of aquatic animals. 34989826 0 23 theme Dietary 0:6 arg1 supplementation 8:22 Dietary supplementation 0:22 Dietary supplementation with microalgae 0:38 Dietary supplementation with microalgae enhances the zebrafish growth performance by modulating immune status and gut microbiota. 34989826 6 24 theme normal 978:983 arg1 state 999:1003 a normal physiological state 976:1003 a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups 976:1099 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 14 25 theme zebrafish 1977:1985 arg1 responses 1964:1972 the intestinal inflammatory responses 1936:1972 the intestinal inflammatory responses of zebrafish 1936:1985 • Microalgae diets attenuated the intestinal inflammatory responses of zebrafish. 34989826 3 26 theme supplementation 434:448 arg1 effects 415:421 the effects 411:421 the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio) 411:659 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 7 27 dep C. 1163:1164 arg1 sorokiniana 1166:1176 sorokiniana 1166:1176 sorokiniana 1166:1176 The expression of neutrophil marker b7r was increased in the C. sorokiniana diet group; after, the zebrafish were challenged with Vibrio anguillarum, improving the ability to resist this disease. 34989826 3 28 theme zebrafish 637:645 arg1 performance 584:594 growth performance 577:594 growth performance 577:594 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 3 28 theme zebrafish 637:645 arg1 status 604:609 immune status 597:609 immune status 597:609 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 3 28 theme zebrafish 637:645 arg1 health 627:632 intestinal health 616:632 intestinal health 616:632 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 2 29 theme aquatic 378:384 arg1 animals 386:392 aquatic animals 378:392 aquatic animals 378:392 Microalgae can be exploited as the basic and primitive food source of aquatic animals. 34989826 15 30 theme microbiota 2025:2034 arg1 composition 2036:2046 the gut microbiota composition 2017:2046 the gut microbiota composition 2017:2046 • Microalgae diets modulated the gut microbiota composition to improve fish health. 34989826 14 31 theme intestinal 1940:1949 arg1 responses 1964:1972 the intestinal inflammatory responses 1936:1972 the intestinal inflammatory responses of zebrafish 1936:1985 • Microalgae diets attenuated the intestinal inflammatory responses of zebrafish. 34989826 0 32 theme zebrafish 53:61 arg1 performance 70:80 the zebrafish growth performance 49:80 the zebrafish growth performance 49:80 Dietary supplementation with microalgae enhances the zebrafish growth performance by modulating immune status and gut microbiota. 34989826 9 33 theme S. 1502:1503 arg1 platensis 1505:1513 S. platensis 1502:1513 S. platensis 1502:1513 To further explain, Cetobacterium was significantly enriched in the S. platensis additive group and Stenotrophomonas was higher in the Schizochytrium sp. 34989826 6 34 dep Schizochytrium 1038:1051 arg1 sp. 1053:1055 sp. 1053:1055 sp. 1053:1055 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 6 34 dep Schizochytrium 1038:1051 arg1 groups 1094:1099 salina dietary groups 1079:1099 salina dietary groups 1079:1099 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 9 35 theme additive 1515:1522 arg1 group 1524:1528 the S. platensis additive group 1498:1528 the S. platensis additive group 1498:1528 To further explain, Cetobacterium was significantly enriched in the S. platensis additive group and Stenotrophomonas was higher in the Schizochytrium sp. 34989826 7 36 theme diet 1178:1181 arg1 group 1183:1187 the C. sorokiniana diet group 1159:1187 the C. sorokiniana diet group 1159:1187 The expression of neutrophil marker b7r was increased in the C. sorokiniana diet group; after, the zebrafish were challenged with Vibrio anguillarum, improving the ability to resist this disease. 34989826 3 37 theme Danio 648:652 arg1 zebrafish 637:645 zebrafish 637:645 zebrafish (Danio rerio) 637:659 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 3 37 theme Danio 648:652 arg1 rerio 654:658 Danio rerio 648:658 Danio rerio 648:658 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 13 38 theme growth 1873:1878 arg1 performance 1880:1890 the growth performance 1869:1890 the growth performance of zebrafish 1869:1903 KEY POINTS: • Microalgae diets enhanced the growth performance of zebrafish. 34989826 2 39 theme basic 343:347 arg1 source 368:373 the basic and primitive food source 339:373 the basic and primitive food source of aquatic animals 339:392 Microalgae can be exploited as the basic and primitive food source of aquatic animals. 34989826 2 39 theme basic 343:347 arg1 Microalgae 308:317 Microalgae 308:317 Microalgae 308:317 Microalgae can be exploited as the basic and primitive food source of aquatic animals. 34989826 1 40 theme high 220:223 arg1 polysaccharides 267:281 polysaccharides 267:281 polysaccharides 267:281 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 40 theme high 220:223 arg1 acids 260:264 fatty acids 254:264 fatty acids 254:264 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 40 theme high 220:223 arg1 proteins 284:291 proteins 284:291 proteins 284:291 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 40 theme high 220:223 arg1 products 237:244 high value-added products 220:244 high value-added products such as fatty acids, polysaccharides, proteins, and pigments 220:305 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 40 theme high 220:223 arg1 pigments 298:305 pigments 298:305 pigments 298:305 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 15 41 theme • 1988:1988 arg1 diets 2001:2005 • Microalgae diets 1988:2005 • Microalgae diets 1988:2005 • Microalgae diets modulated the gut microbiota composition to improve fish health. 34989826 7 42 theme C. 1163:1164 arg1 group 1183:1187 the C. sorokiniana diet group 1159:1187 the C. sorokiniana diet group 1159:1187 The expression of neutrophil marker b7r was increased in the C. sorokiniana diet group; after, the zebrafish were challenged with Vibrio anguillarum, improving the ability to resist this disease. 34989826 7 43 theme neutrophil 1120:1129 arg1 b7r 1138:1140 neutrophil marker b7r 1120:1140 neutrophil marker b7r 1120:1140 The expression of neutrophil marker b7r was increased in the C. sorokiniana diet group; after, the zebrafish were challenged with Vibrio anguillarum, improving the ability to resist this disease. 34989826 3 44 from effects 415:421 arg1 performance 584:594 growth performance 577:594 growth performance 577:594 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 3 44 from effects 415:421 arg1 status 604:609 immune status 597:609 immune status 597:609 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 3 44 from effects 415:421 arg1 health 627:632 intestinal health 616:632 intestinal health 616:632 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 10 45 theme other 1615:1619 arg1 groups 1621:1626 the other groups 1611:1626 the other groups 1611:1626 additive group than in the other groups. 34989826 13 46 theme Microalgae 1843:1852 arg1 diets 1854:1858 Microalgae diets 1843:1858 Microalgae diets 1843:1858 KEY POINTS: • Microalgae diets enhanced the growth performance of zebrafish. 34989826 6 47 theme dietary 1086:1092 arg1 groups 1094:1099 salina dietary groups 1079:1099 salina dietary groups 1079:1099 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 1 48 theme various 169:175 arg1 habitats 177:184 various habitats 169:184 various habitats around the globe 169:201 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 9 49 theme Schizochytrium 1569:1582 arg1 sp 1584:1585 the Schizochytrium sp 1565:1585 the Schizochytrium sp 1565:1585 To further explain, Cetobacterium was significantly enriched in the S. platensis additive group and Stenotrophomonas was higher in the Schizochytrium sp. 34989826 13 50 theme KEY 1829:1831 arg1 POINTS 1833:1838 KEY POINTS 1829:1838 KEY POINTS 1829:1838 KEY POINTS: • Microalgae diets enhanced the growth performance of zebrafish. 34989826 3 51 dep performance 584:594 arg1 the 573:575 the 573:575 the 573:575 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 6 52 theme gene 898:901 arg1 level 914:918 the gene expression level 894:918 the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β 894:971 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 6 53 theme S. 1058:1059 arg1 platensis 1061:1069 S. platensis 1058:1069 S. platensis 1058:1069 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 6 53 theme S. 1058:1059 arg1 intestine 1012:1020 the intestine 1008:1020 the intestine 1008:1020 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 11 54 theme microalgae 1691:1700 arg1 groups 1707:1712 all tested microalgae diet groups 1680:1712 all tested microalgae diet groups 1680:1712 Conversely, harmful bacteria Mycoplasma reduced in all tested microalgae diet groups. 34989826 3 55 with supplementation 434:448 arg1 zofingiensis 534:545 Chromochloris zofingiensis 520:545 Chromochloris zofingiensis 520:545 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 3 55 with supplementation 434:448 arg1 salina 563:568 Dunaliella salina 552:568 Dunaliella salina 552:568 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 3 55 with supplementation 434:448 arg1 sp. 470:472 Schizochytrium sp. 455:472 Schizochytrium sp. 455:472 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 3 55 with supplementation 434:448 arg1 platensis 485:493 Spirulina platensis 475:493 Spirulina platensis 475:493 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 3 55 with supplementation 434:448 arg1 sorokiniana 507:517 Chloroella sorokiniana 496:517 Chloroella sorokiniana 496:517 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 4 56 dep D. 775:776 arg1 sp 818:819 sp 818:819 sp 818:819 The results showed that these five microalgae diets could improve the feed conversion rate (FCR), especially the D. salina (FCR = 1.02%) and Schizochytrium sp. 34989826 4 56 dep D. 775:776 arg1 salina 778:783 D. salina (FCR = 1.02%) 775:797 D. salina (FCR = 1.02%) 775:797 The results showed that these five microalgae diets could improve the feed conversion rate (FCR), especially the D. salina (FCR = 1.02%) and Schizochytrium sp. 34989826 4 56 dep D. 775:776 arg1 the 771:773 the 771:773 the 771:773 The results showed that these five microalgae diets could improve the feed conversion rate (FCR), especially the D. salina (FCR = 1.02%) and Schizochytrium sp. 34989826 8 57 theme gut 1353:1355 arg1 microbiota 1357:1366 the gut microbiota 1349:1366 the gut microbiota of fish 1349:1374 We also found that microalgae diets could regulate the gut microbiota of fish as well as increase the relative abundance of probiotics. 34989826 6 58 theme microalgae 867:876 arg1 diets 878:882 the microalgae diets 863:882 the microalgae diets 863:882 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 1 59 from rich 212:215 arg1 polysaccharides 267:281 polysaccharides 267:281 polysaccharides 267:281 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 59 from rich 212:215 arg1 acids 260:264 fatty acids 254:264 fatty acids 254:264 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 59 from rich 212:215 arg1 proteins 284:291 proteins 284:291 proteins 284:291 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 59 from rich 212:215 arg1 products 237:244 high value-added products 220:244 high value-added products such as fatty acids, polysaccharides, proteins, and pigments 220:305 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 59 from rich 212:215 arg1 pigments 298:305 pigments 298:305 pigments 298:305 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 11 60 dep reduced 1669:1675 arg1 Mycoplasma 1658:1667 Mycoplasma 1658:1667 Mycoplasma 1658:1667 Conversely, harmful bacteria Mycoplasma reduced in all tested microalgae diet groups. 34989826 7 61 theme b7r 1138:1140 arg1 expression 1106:1115 The expression 1102:1115 The expression of neutrophil marker b7r 1102:1140 The expression of neutrophil marker b7r was increased in the C. sorokiniana diet group; after, the zebrafish were challenged with Vibrio anguillarum, improving the ability to resist this disease. 34989826 3 62 theme immune 597:602 arg1 status 604:609 immune status 597:609 immune status 597:609 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 0 63 theme immune 96:101 arg1 status 103:108 immune status 96:108 immune status 96:108 Dietary supplementation with microalgae enhances the zebrafish growth performance by modulating immune status and gut microbiota. 34989826 1 64 from habitats 177:184 arg1 abundant 157:164 abundant 157:164 abundant 157:164 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 6 65 theme cytokines 944:952 arg1 level 914:918 the gene expression level 894:918 the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β 894:971 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 6 66 dep cytokines 944:952 arg1 cytokines 944:952 the pro-inflammatory cytokines 923:952 the pro-inflammatory cytokines IL6, IL8, and IL1β 923:971 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 6 66 dep cytokines 944:952 arg1 IL8 959:961 IL8 959:961 IL8 959:961 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 6 66 dep cytokines 944:952 arg1 IL1β 968:971 IL1β 968:971 IL1β 968:971 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 6 66 dep cytokines 944:952 arg1 IL6 954:956 IL6 954:956 IL6 954:956 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 12 67 theme fish 1823:1826 arg1 microalgae 1746:1755 these microalgae 1740:1755 these microalgae 1740:1755 Our study indicated that these microalgae could serve as a food source supplement and benefit the health of fish. 34989826 12 67 theme fish 1823:1826 arg1 health 1813:1818 the health 1809:1818 the health of fish 1809:1826 Our study indicated that these microalgae could serve as a food source supplement and benefit the health of fish. 34989826 12 67 theme fish 1823:1826 arg1 supplement 1786:1795 a food source supplement 1772:1795 a food source supplement 1772:1795 Our study indicated that these microalgae could serve as a food source supplement and benefit the health of fish. 34989826 14 68 theme Microalgae 1908:1917 arg1 diets 1919:1923 • Microalgae diets 1906:1923 • Microalgae diets 1906:1923 • Microalgae diets attenuated the intestinal inflammatory responses of zebrafish. 34989826 4 69 theme feed 732:735 arg1 FCR 754:756 FCR 754:756 FCR 754:756 The results showed that these five microalgae diets could improve the feed conversion rate (FCR), especially the D. salina (FCR = 1.02%) and Schizochytrium sp. 34989826 4 69 theme feed 732:735 arg1 rate 748:751 the feed conversion rate 728:751 the feed conversion rate (FCR) 728:757 The results showed that these five microalgae diets could improve the feed conversion rate (FCR), especially the D. salina (FCR = 1.02%) and Schizochytrium sp. 34989826 8 70 theme probiotics 1422:1431 arg1 abundance 1409:1417 the relative abundance 1396:1417 the relative abundance of probiotics 1396:1431 We also found that microalgae diets could regulate the gut microbiota of fish as well as increase the relative abundance of probiotics. 34989826 2 71 theme food 363:366 arg1 source 368:373 the basic and primitive food source 339:373 the basic and primitive food source of aquatic animals 339:392 Microalgae can be exploited as the basic and primitive food source of aquatic animals. 34989826 2 71 theme food 363:366 arg1 Microalgae 308:317 Microalgae 308:317 Microalgae 308:317 Microalgae can be exploited as the basic and primitive food source of aquatic animals. 34989826 6 72 theme physiological 985:997 arg1 state 999:1003 a normal physiological state 976:1003 a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups 976:1099 Moreover, the microalgae diets decreased the gene expression level of the pro-inflammatory cytokines IL6, IL8, and IL1β at a normal physiological state of the intestine, especially the Schizochytrium sp., S. platensis, and D. salina dietary groups. 34989826 1 73 from products 237:244 arg1 rich 212:215 rich 212:215 rich 212:215 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 5 74 dep additive 836:843 arg1 % 833:833 FCR = 1.20% 823:833 FCR = 1.20% 823:833 (FCR = 1.20%) additive groups. 34989826 2 75 theme animals 386:392 arg1 source 368:373 the basic and primitive food source 339:373 the basic and primitive food source of aquatic animals 339:392 Microalgae can be exploited as the basic and primitive food source of aquatic animals. 34989826 2 75 theme animals 386:392 arg1 Microalgae 308:317 Microalgae 308:317 Microalgae 308:317 Microalgae can be exploited as the basic and primitive food source of aquatic animals. 34989826 12 76 theme food 1774:1777 arg1 microalgae 1746:1755 these microalgae 1740:1755 these microalgae 1740:1755 Our study indicated that these microalgae could serve as a food source supplement and benefit the health of fish. 34989826 12 76 theme food 1774:1777 arg1 health 1813:1818 the health 1809:1818 the health of fish 1809:1826 Our study indicated that these microalgae could serve as a food source supplement and benefit the health of fish. 34989826 12 76 theme food 1774:1777 arg1 supplement 1786:1795 a food source supplement 1772:1795 a food source supplement 1772:1795 Our study indicated that these microalgae could serve as a food source supplement and benefit the health of fish. 34989826 15 77 theme gut 2021:2023 arg1 composition 2036:2046 the gut microbiota composition 2017:2046 the gut microbiota composition 2017:2046 • Microalgae diets modulated the gut microbiota composition to improve fish health. 34989826 14 78 theme inflammatory 1951:1962 arg1 responses 1964:1972 the intestinal inflammatory responses 1936:1972 the intestinal inflammatory responses of zebrafish 1936:1985 • Microalgae diets attenuated the intestinal inflammatory responses of zebrafish. 34989826 3 79 theme intestinal 616:625 arg1 health 627:632 intestinal health 616:632 intestinal health 616:632 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 13 80 theme zebrafish 1895:1903 arg1 performance 1880:1890 the growth performance 1869:1890 the growth performance of zebrafish 1869:1903 KEY POINTS: • Microalgae diets enhanced the growth performance of zebrafish. 34989826 3 81 theme dietary 426:432 arg1 supplementation 434:448 dietary supplementation 426:448 dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina 426:568 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 0 82 theme growth 63:68 arg1 performance 70:80 the zebrafish growth performance 49:80 the zebrafish growth performance 49:80 Dietary supplementation with microalgae enhances the zebrafish growth performance by modulating immune status and gut microbiota. 34989826 0 83 with supplementation 8:22 arg1 microalgae 29:38 microalgae 29:38 microalgae 29:38 Dietary supplementation with microalgae enhances the zebrafish growth performance by modulating immune status and gut microbiota. 34989826 3 84 theme Spirulina 475:483 arg1 platensis 485:493 Spirulina platensis 475:493 Spirulina platensis 475:493 We investigated the effects of dietary supplementation with Schizochytrium sp., Spirulina platensis, Chloroella sorokiniana, Chromochloris zofingiensis, and Dunaliella salina on the growth performance, immune status, and intestinal health of zebrafish (Danio rerio). 34989826 15 85 theme Microalgae 1990:1999 arg1 diets 2001:2005 • Microalgae diets 1988:2005 • Microalgae diets 1988:2005 • Microalgae diets modulated the gut microbiota composition to improve fish health. 34989826 10 86 theme additive 1588:1595 arg1 group 1597:1601 additive group 1588:1601 additive group 1588:1601 additive group than in the other groups. 34989826 8 87 theme microalgae 1317:1326 arg1 diets 1328:1332 microalgae diets 1317:1332 microalgae diets 1317:1332 We also found that microalgae diets could regulate the gut microbiota of fish as well as increase the relative abundance of probiotics. 34989826 1 88 theme value-added 225:235 arg1 polysaccharides 267:281 polysaccharides 267:281 polysaccharides 267:281 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 88 theme value-added 225:235 arg1 acids 260:264 fatty acids 254:264 fatty acids 254:264 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 88 theme value-added 225:235 arg1 proteins 284:291 proteins 284:291 proteins 284:291 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 88 theme value-added 225:235 arg1 products 237:244 high value-added products 220:244 high value-added products such as fatty acids, polysaccharides, proteins, and pigments 220:305 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 34989826 1 88 theme value-added 225:235 arg1 pigments 298:305 pigments 298:305 pigments 298:305 Microalgae are known to be abundant in various habitats around the globe, and are rich in high value-added products such as fatty acids, polysaccharides, proteins, and pigments. 36297292 6 0 theme Gi-MRSW 1140:1146 arg1 potential 1127:1135 the immunomodulatory potential 1106:1135 the immunomodulatory potential of Gi-MRSW 1106:1146 Moreover, the immunomodulatory potential of Gi-MRSW was evaluated using RAW 264.7 murine macrophage as a study model. 36297292 4 1 with purification 732:743 arg1 sizes 848:852 different pore sizes 833:852 different pore sizes 833:852 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 3 2 theme imperialis 506:515 arg1 basidiomata 480:490 the basidiomata 476:490 the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) 476:577 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 3 3 with fraction 701:708 arg1 ethanol 715:721 ethanol 715:721 ethanol 715:721 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 0 4 from Effect 17:22 arg1 imperialis 94:103 the Mushroom-Forming Basidiomycete Gymnopilus imperialis 48:103 the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota) 48:135 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 36297292 7 5 theme treated 1273:1279 arg1 samples 1281:1287 treated samples 1273:1287 treated samples 1273:1287 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 6 6 theme immunomodulatory 1110:1125 arg1 potential 1127:1135 the immunomodulatory potential 1106:1135 the immunomodulatory potential of Gi-MRSW 1106:1146 Moreover, the immunomodulatory potential of Gi-MRSW was evaluated using RAW 264.7 murine macrophage as a study model. 36297292 3 7 theme fraction 701:708 arg1 precipitation 669:681 the precipitation 665:681 the precipitation of polysaccharide fraction with ethanol 665:721 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 4 8 with dialysis 819:826 arg1 sizes 848:852 different pore sizes 833:852 different pore sizes 833:852 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 7 9 theme polarization 1418:1429 arg1 phenotype 1431:1439 the M1 polarization phenotype 1411:1439 the M1 polarization phenotype 1411:1439 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 3 10 theme polysaccharide 686:699 arg1 fraction 701:708 polysaccharide fraction 686:708 polysaccharide fraction with ethanol 686:721 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 5 11 theme Gi-MRSW 991:997 arg1 fractions 1011:1019 the Gi-MRSW and Gi-SFME fractions 987:1019 the Gi-MRSW and Gi-SFME fractions 987:1019 According to monosaccharide composition and 13C-NMR data, the Gi-MRSW and Gi-SFME fractions showed to be composed mainly of β-glucans and Gi-PFME by a heterogalactan. 36297292 4 12 theme solution 782:789 arg1 precipitation 791:803 Fehling solution precipitation 774:803 Fehling solution precipitation 774:803 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 3 13 theme basidiomata 480:490 arg1 extract 465:471 the aqueous extract 453:471 the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) 453:577 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 4 14 theme polysaccharide 871:884 arg1 fractions 886:894 three main polysaccharide fractions 860:894 three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME) 860:926 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 4 14 theme polysaccharide 871:884 arg1 Gi-PFME 906:912 Gi-PFME 906:912 Gi-PFME 906:912 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 4 14 theme polysaccharide 871:884 arg1 Gi-SFME 919:925 Gi-SFME 919:925 Gi-SFME 919:925 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 4 14 theme polysaccharide 871:884 arg1 Gi-MRSW 897:903 Gi-MRSW 897:903 Gi-MRSW 897:903 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 7 15 theme synthase 1335:1342 arg1 expression 1298:1307 the expression 1294:1307 the expression of inducible nitric oxide synthase (iNOS) 1294:1349 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 1 16 theme basidiomycetes 191:204 arg1 genus 182:186 a widely distributed genus 161:186 a widely distributed genus of basidiomycetes 161:204 Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. 36297292 4 17 theme main 866:869 arg1 fractions 886:894 three main polysaccharide fractions 860:894 three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME) 860:926 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 4 17 theme main 866:869 arg1 Gi-PFME 906:912 Gi-PFME 906:912 Gi-PFME 906:912 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 4 17 theme main 866:869 arg1 Gi-SFME 919:925 Gi-SFME 919:925 Gi-SFME 919:925 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 4 17 theme main 866:869 arg1 Gi-MRSW 897:903 Gi-MRSW 897:903 Gi-MRSW 897:903 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 4 18 dep fractions 886:894 arg1 fractions 886:894 three main polysaccharide fractions 860:894 three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME) 860:926 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 4 18 dep fractions 886:894 arg1 Gi-PFME 906:912 Gi-PFME 906:912 Gi-PFME 906:912 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 4 18 dep fractions 886:894 arg1 Gi-SFME 919:925 Gi-SFME 919:925 Gi-SFME 919:925 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 4 18 dep fractions 886:894 arg1 Gi-MRSW 897:903 Gi-MRSW 897:903 Gi-MRSW 897:903 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 6 19 dep RAW 1168:1170 arg1 macrophage 1185:1194 murine macrophage 1178:1194 RAW 264.7 murine macrophage 1168:1194 Moreover, the immunomodulatory potential of Gi-MRSW was evaluated using RAW 264.7 murine macrophage as a study model. 36297292 3 20 dep imperialis 506:515 arg1 Basidiomycota 518:530 Basidiomycota 518:530 Basidiomycota 518:530 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 3 20 dep imperialis 506:515 arg1 Hymenogastraceae 561:576 Hymenogastraceae 561:576 Hymenogastraceae 561:576 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 0 21 theme Immunomodulatory 0:15 arg1 Effect 17:22 Immunomodulatory Effect 0:22 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 0:136 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 36297292 4 22 theme freeze-thawing 748:761 arg1 processes 763:771 freeze-thawing processes 748:771 freeze-thawing processes 748:771 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 3 23 theme present 438:444 arg1 study 446:450 the present study 434:450 the present study 434:450 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 0 24 theme Polysaccharides 27:41 arg1 Effect 17:22 Immunomodulatory Effect 0:22 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 0:136 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 36297292 4 25 theme different 833:841 arg1 sizes 848:852 different pore sizes 833:852 different pore sizes 833:852 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 0 26 dep imperialis 94:103 arg1 Basidiomycota 122:134 Basidiomycota 122:134 Basidiomycota 122:134 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 36297292 0 26 dep imperialis 94:103 arg1 Agaricomycetes 106:119 Agaricomycetes 106:119 Agaricomycetes 106:119 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 36297292 1 27 theme tropical 221:228 arg1 regions 230:236 tropical regions 221:236 tropical regions 221:236 Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. 36297292 1 27 theme tropical 221:228 arg1 Paraguay 278:285 Paraguay 278:285 Paraguay 278:285 Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. 36297292 1 27 theme tropical 221:228 arg1 Brazil 292:297 Brazil 292:297 Brazil 292:297 Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. 36297292 1 27 theme tropical 221:228 arg1 Australia 267:275 Australia 267:275 Australia 267:275 Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. 36297292 5 28 theme 13C-NMR 973:979 arg1 data 981:984 13C-NMR data 973:984 13C-NMR data 973:984 According to monosaccharide composition and 13C-NMR data, the Gi-MRSW and Gi-SFME fractions showed to be composed mainly of β-glucans and Gi-PFME by a heterogalactan. 36297292 4 29 with precipitation 791:803 arg1 sizes 848:852 different pore sizes 833:852 different pore sizes 833:852 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 7 30 theme M1 1415:1416 arg1 phenotype 1431:1439 the M1 polarization phenotype 1411:1439 the M1 polarization phenotype 1411:1439 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 7 31 from imperialis 1392:1401 arg1 Gi-MRSW 1376:1382 the fraction Gi-MRSW 1363:1382 the fraction Gi-MRSW from G. imperialis 1363:1401 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 6 32 theme murine 1178:1183 arg1 macrophage 1185:1194 murine macrophage 1178:1194 RAW 264.7 murine macrophage 1168:1194 Moreover, the immunomodulatory potential of Gi-MRSW was evaluated using RAW 264.7 murine macrophage as a study model. 36297292 7 33 theme inducible 1312:1320 arg1 iNOS 1345:1348 iNOS 1345:1348 iNOS 1345:1348 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 7 33 theme inducible 1312:1320 arg1 synthase 1335:1342 inducible nitric oxide synthase 1312:1342 inducible nitric oxide synthase (iNOS) 1312:1349 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 0 34 from imperialis 94:103 arg1 Polysaccharides 27:41 Polysaccharides 27:41 Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota) 27:135 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 36297292 0 34 from imperialis 94:103 arg1 Effect 17:22 Immunomodulatory Effect 0:22 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 0:136 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 36297292 3 35 theme accelerated 605:615 arg1 technique 642:650 the accelerated solvent extraction (ASE) technique 601:650 the accelerated solvent extraction (ASE) technique 601:650 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 3 36 theme aqueous 457:463 arg1 extract 465:471 the aqueous extract 453:471 the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) 453:577 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 0 37 theme Basidiomycete 69:81 arg1 imperialis 94:103 the Mushroom-Forming Basidiomycete Gymnopilus imperialis 48:103 the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota) 48:135 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 36297292 7 38 theme nitric 1218:1223 arg1 oxide 1225:1229 The nitric oxide 1214:1229 The nitric oxide production 1214:1240 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 4 39 theme Further 724:730 arg1 purification 732:743 Further purification 724:743 Further purification by freeze-thawing processes 724:771 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 0 40 theme Mushroom-Forming 52:67 arg1 imperialis 94:103 the Mushroom-Forming Basidiomycete Gymnopilus imperialis 48:103 the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota) 48:135 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 36297292 6 41 theme study 1201:1205 arg1 RAW 1168:1170 RAW 264.7 1168:1176 RAW 264.7 murine macrophage 1168:1194 Moreover, the immunomodulatory potential of Gi-MRSW was evaluated using RAW 264.7 murine macrophage as a study model. 36297292 6 41 theme study 1201:1205 arg1 model 1207:1211 a study model 1199:1211 a study model 1199:1211 Moreover, the immunomodulatory potential of Gi-MRSW was evaluated using RAW 264.7 murine macrophage as a study model. 36297292 7 42 theme G. 1389:1390 arg1 imperialis 1392:1401 G. imperialis 1389:1401 G. imperialis 1389:1401 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 3 43 theme Gymnopilus 495:504 arg1 imperialis 506:515 Gymnopilus imperialis 495:515 Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) 495:577 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 7 44 theme fraction 1367:1374 arg1 Gi-MRSW 1376:1382 the fraction Gi-MRSW 1363:1382 the fraction Gi-MRSW from G. imperialis 1363:1401 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 4 45 theme pore 843:846 arg1 sizes 848:852 different pore sizes 833:852 different pore sizes 833:852 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 2 46 theme bioactive 338:346 arg1 compounds 348:356 interesting bioactive compounds 326:356 interesting bioactive compounds 326:356 This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. 36297292 2 46 theme bioactive 338:346 arg1 lectins 422:428 lectins 422:428 lectins 422:428 This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. 36297292 2 46 theme bioactive 338:346 arg1 oligoisoprenoids 385:400 oligoisoprenoids 385:400 oligoisoprenoids 385:400 This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. 36297292 2 46 theme bioactive 338:346 arg1 sesquiterpenoids 367:382 sesquiterpenoids 367:382 sesquiterpenoids 367:382 This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. 36297292 2 46 theme bioactive 338:346 arg1 styrylpyrones 403:415 styrylpyrones 403:415 styrylpyrones 403:415 This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. 36297292 4 47 theme Fehling 774:780 arg1 precipitation 791:803 Fehling solution precipitation 774:803 Fehling solution precipitation 774:803 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 1 48 theme world 245:249 arg1 regions 230:236 tropical regions 221:236 tropical regions 221:236 Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. 36297292 1 48 theme world 245:249 arg1 Paraguay 278:285 Paraguay 278:285 Paraguay 278:285 Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. 36297292 1 48 theme world 245:249 arg1 Brazil 292:297 Brazil 292:297 Brazil 292:297 Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. 36297292 1 48 theme world 245:249 arg1 Australia 267:275 Australia 267:275 Australia 267:275 Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. 36297292 5 49 theme Gi-SFME 1003:1009 arg1 fractions 1011:1019 the Gi-MRSW and Gi-SFME fractions 987:1019 the Gi-MRSW and Gi-SFME fractions 987:1019 According to monosaccharide composition and 13C-NMR data, the Gi-MRSW and Gi-SFME fractions showed to be composed mainly of β-glucans and Gi-PFME by a heterogalactan. 36297292 4 50 theme membrane 810:817 arg1 dialysis 819:826 membrane dialysis 810:826 membrane dialysis with different pore sizes 810:852 Further purification by freeze-thawing processes, Fehling solution precipitation, and membrane dialysis with different pore sizes yield three main polysaccharide fractions (Gi-MRSW, Gi-PFME, and Gi-SFME). 36297292 2 51 theme interesting 326:336 arg1 compounds 348:356 interesting bioactive compounds 326:356 interesting bioactive compounds 326:356 This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. 36297292 2 51 theme interesting 326:336 arg1 lectins 422:428 lectins 422:428 lectins 422:428 This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. 36297292 2 51 theme interesting 326:336 arg1 oligoisoprenoids 385:400 oligoisoprenoids 385:400 oligoisoprenoids 385:400 This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. 36297292 2 51 theme interesting 326:336 arg1 sesquiterpenoids 367:382 sesquiterpenoids 367:382 sesquiterpenoids 367:382 This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. 36297292 2 51 theme interesting 326:336 arg1 styrylpyrones 403:415 styrylpyrones 403:415 styrylpyrones 403:415 This genus biosynthesizes interesting bioactive compounds, such as sesquiterpenoids, oligoisoprenoids, styrylpyrones, and lectins. 36297292 5 52 theme monosaccharide 942:955 arg1 composition 957:967 monosaccharide composition 942:967 monosaccharide composition 942:967 According to monosaccharide composition and 13C-NMR data, the Gi-MRSW and Gi-SFME fractions showed to be composed mainly of β-glucans and Gi-PFME by a heterogalactan. 36297292 7 53 theme nitric 1322:1327 arg1 iNOS 1345:1348 iNOS 1345:1348 iNOS 1345:1348 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 7 53 theme nitric 1322:1327 arg1 synthase 1335:1342 inducible nitric oxide synthase 1312:1342 inducible nitric oxide synthase (iNOS) 1312:1349 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 3 54 theme solvent 617:623 arg1 extraction 625:634 solvent extraction 617:634 the accelerated solvent extraction (ASE) technique 601:650 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 3 54 theme solvent 617:623 arg1 ASE 637:639 ASE 637:639 ASE 637:639 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 7 55 theme oxide 1329:1333 arg1 iNOS 1345:1348 iNOS 1345:1348 iNOS 1345:1348 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 7 55 theme oxide 1329:1333 arg1 synthase 1335:1342 inducible nitric oxide synthase 1312:1342 inducible nitric oxide synthase (iNOS) 1312:1349 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 36297292 0 56 theme Gymnopilus 83:92 arg1 imperialis 94:103 the Mushroom-Forming Basidiomycete Gymnopilus imperialis 48:103 the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota) 48:135 Immunomodulatory Effect of Polysaccharides from the Mushroom-Forming Basidiomycete Gymnopilus imperialis (Agaricomycetes, Basidiomycota). 36297292 3 57 theme extraction 625:634 arg1 technique 642:650 the accelerated solvent extraction (ASE) technique 601:650 the accelerated solvent extraction (ASE) technique 601:650 In the present study, the aqueous extract of the basidiomata of Gymnopilus imperialis (Basidiomycota, Agaricomycetes, Agaricales, Hymenogastraceae) was obtained by using the accelerated solvent extraction (ASE) technique, followed by the precipitation of polysaccharide fraction with ethanol. 36297292 1 58 theme distributed 170:180 arg1 genus 182:186 a widely distributed genus 161:186 a widely distributed genus of basidiomycetes 161:204 Gymnopilus consists of a widely distributed genus of basidiomycetes, especially in tropical regions of the world, such as Japan, Australia, Paraguay, and Brazil. 36297292 7 59 theme oxide 1225:1229 arg1 production 1231:1240 The nitric oxide production 1214:1240 The nitric oxide production 1214:1240 The nitric oxide production was significantly increased in treated samples, and the expression of inducible nitric oxide synthase (iNOS) showed that the fraction Gi-MRSW from G. imperialis induces the M1 polarization phenotype. 35085842 14 0 theme bulking 2190:2196 arg1 prevention 2152:2161 prevention 2152:2161 prevention 2152:2161 Therefore, QQ is a potential strategy for the prevention and control of filamentous bulking. 35085842 14 0 theme bulking 2190:2196 arg1 control 2167:2173 control 2167:2173 control 2167:2173 Therefore, QQ is a potential strategy for the prevention and control of filamentous bulking. 35085842 12 1 theme vanillin 1994:2001 arg1 50 mg/L 1983:1989 50 mg/L 1983:1989 50 mg/L of vanillin 1983:2001 The WT between bacteria with 50 mg/L of vanillin basically did not change. 35085842 4 2 theme related 733:739 arg1 gene 728:731 the hdtS gene 719:731 the hdtS gene related to the synthesis of C6HSL with increases in the population density 719:806 The filamentous bacteria gradually evolved the hdtS gene related to the synthesis of C6HSL with increases in the population density. 35085842 5 3 dep Triggered 809:817 arg1 QS 819:820 QS 819:820 QS 819:820 Triggered QS by filamentous bacteria proliferation induced variation in the composition and structure of EPS within the sludge flocs. 35085842 0 4 theme New 0:2 arg1 insight 4:10 New insight 0:10 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 0:143 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 35085842 1 5 theme filamentous 183:193 arg1 bulking 195:201 filamentous bulking 183:201 filamentous bulking 183:201 The microcosmic mechanisms underlying filamentous bulking remain unclear. 35085842 6 6 theme EPS 976:978 arg1 content 961:967 The proteins (PN) content 943:967 The proteins (PN) content of the EPS 943:978 The proteins (PN) content of the EPS increased evidently from 40.06 ± 2.41 mg/g VSS to 110.32 ± 4.32 mg/g VSS, and the polysaccharides (PS) content slightly increased during filamentous bulking. 35085842 3 7 theme C6HSL 584:588 arg1 concentration 567:579 the concentration 563:579 the concentration of C6HSL 563:588 The results indicated that the concentration of C6HSL increased from 22.08±3.22 ng/g VSS to 81.42±5.98 ng/g VSS during filamentous bulking. 35085842 0 8 theme floc 115:118 arg1 stability 120:128 sludge floc stability 108:128 sludge floc stability 108:128 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 35085842 10 9 theme filamentous 1778:1788 arg1 bacteria 1790:1797 the filamentous bacteria 1774:1797 the filamentous bacteria 1774:1797 Variation in the physicochemical properties of EPS induced by QS in the filamentous bacteria markedly restrained adhesion between the filamentous bacteria and floc-forming bacteria. 35085842 8 10 dep 0.99 1354:1357 arg1 to 1351:1352 to 1351:1352 to 1351:1352 The α-helix/(β-sheet+random coil) ratio evidently increased from 0.76 to 0.99 during filamentous bulking, revealing that the proteins were tightly structured, which prevented the exposure of inner hydrophobic groups. 35085842 15 11 theme new 2219:2221 arg1 information 2223:2233 new information 2219:2233 new information regarding the microcosmic mechanisms of filamentous bulking 2219:2293 This study provides new information regarding the microcosmic mechanisms of filamentous bulking. 35085842 8 12 theme α-helix/ 1285:1292 arg1 ratio 1315:1319 The α-helix/(β-sheet+random coil) ratio 1281:1319 The α-helix/(β-sheet+random coil) ratio 1281:1319 The α-helix/(β-sheet+random coil) ratio evidently increased from 0.76 to 0.99 during filamentous bulking, revealing that the proteins were tightly structured, which prevented the exposure of inner hydrophobic groups. 35085842 2 13 theme polymeric 245:253 arg1 EPS 267:269 EPS 267:269 EPS 267:269 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 2 13 theme polymeric 245:253 arg1 substances 255:264 extracellular polymeric substances 231:264 extracellular polymeric substances (EPS) governed by quorum sensing (QS) 231:302 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 15 14 theme bulking 2287:2293 arg1 mechanisms 2261:2270 the microcosmic mechanisms 2245:2270 the microcosmic mechanisms of filamentous bulking 2245:2293 This study provides new information regarding the microcosmic mechanisms of filamentous bulking. 35085842 8 15 theme β-sheet+random 1294:1307 arg1 ratio 1315:1319 The α-helix/(β-sheet+random coil) ratio 1281:1319 The α-helix/(β-sheet+random coil) ratio 1281:1319 The α-helix/(β-sheet+random coil) ratio evidently increased from 0.76 to 0.99 during filamentous bulking, revealing that the proteins were tightly structured, which prevented the exposure of inner hydrophobic groups. 35085842 11 16 theme QS 1940:1941 arg1 inhibitor 1943:1951 a QS inhibitor 1938:1951 a QS inhibitor 1938:1951 The production of PN in the EPS and the expression of the hdtS gene were inhibited by vanillin, which served as a QS inhibitor. 35085842 11 16 theme QS 1940:1941 arg1 vanillin 1912:1919 vanillin 1912:1919 vanillin 1912:1919 The production of PN in the EPS and the expression of the hdtS gene were inhibited by vanillin, which served as a QS inhibitor. 35085842 9 17 theme total 1502:1506 arg1 energy 1508:1513 The total energy 1498:1513 The total energy of the interaction (WT) between bacteria 1498:1554 The total energy of the interaction (WT) between bacteria increased during sludge bulking, which resulted in the weakening of sludge aggregation. 35085842 8 18 theme inner 1472:1476 arg1 groups 1490:1495 inner hydrophobic groups 1472:1495 inner hydrophobic groups 1472:1495 The α-helix/(β-sheet+random coil) ratio evidently increased from 0.76 to 0.99 during filamentous bulking, revealing that the proteins were tightly structured, which prevented the exposure of inner hydrophobic groups. 35085842 13 19 theme vanillin 2096:2103 arg1 addition 2084:2091 the addition 2080:2091 the addition of vanillin 2080:2103 Filamentous bulking was significantly inhibited by the addition of vanillin. 35085842 3 20 theme 81.42±5.98 ng/g 628:642 arg1 VSS 644:646 81.42±5.98 ng/g VSS 628:646 81.42±5.98 ng/g VSS 628:646 The results indicated that the concentration of C6HSL increased from 22.08±3.22 ng/g VSS to 81.42±5.98 ng/g VSS during filamentous bulking. 35085842 2 21 theme settling 494:501 arg1 sludge 487:492 sludge settling 487:501 sludge settling 487:501 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 8 22 theme groups 1490:1495 arg1 exposure 1460:1467 the exposure 1456:1467 the exposure of inner hydrophobic groups 1456:1495 The α-helix/(β-sheet+random coil) ratio evidently increased from 0.76 to 0.99 during filamentous bulking, revealing that the proteins were tightly structured, which prevented the exposure of inner hydrophobic groups. 35085842 9 23 theme interaction 1522:1532 arg1 energy 1508:1513 The total energy 1498:1513 The total energy of the interaction (WT) between bacteria 1498:1554 The total energy of the interaction (WT) between bacteria increased during sludge bulking, which resulted in the weakening of sludge aggregation. 35085842 4 24 theme hdtS 723:726 arg1 gene 728:731 the hdtS gene 719:731 the hdtS gene related to the synthesis of C6HSL with increases in the population density 719:806 The filamentous bacteria gradually evolved the hdtS gene related to the synthesis of C6HSL with increases in the population density. 35085842 0 25 theme AHL-mediated 63:74 arg1 sensing 83:89 AHL-mediated quorum sensing 63:89 AHL-mediated quorum sensing 63:89 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 35085842 12 26 with WT 1958:1959 arg1 50 mg/L 1983:1989 50 mg/L 1983:1989 50 mg/L of vanillin 1983:2001 The WT between bacteria with 50 mg/L of vanillin basically did not change. 35085842 5 27 theme sludge 929:934 arg1 flocs 936:940 the sludge flocs 925:940 the sludge flocs 925:940 Triggered QS by filamentous bacteria proliferation induced variation in the composition and structure of EPS within the sludge flocs. 35085842 6 28 theme 40.06 ± 2.41 mg/g 1005:1021 arg1 VSS 1023:1025 40.06 ± 2.41 mg/g VSS 1005:1025 40.06 ± 2.41 mg/g VSS to 110.32 ± 4.32 mg/g VSS 1005:1051 The proteins (PN) content of the EPS increased evidently from 40.06 ± 2.41 mg/g VSS to 110.32 ± 4.32 mg/g VSS, and the polysaccharides (PS) content slightly increased during filamentous bulking. 35085842 0 29 theme sensing 83:89 arg1 role 55:58 Potential role 45:58 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 0:143 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 35085842 4 30 theme population 789:798 arg1 density 800:806 the population density 785:806 the population density 785:806 The filamentous bacteria gradually evolved the hdtS gene related to the synthesis of C6HSL with increases in the population density. 35085842 7 31 theme relative 1199:1206 arg1 hydrophobicity 1208:1221 the relative hydrophobicity 1195:1221 the relative hydrophobicity of the sludge 1195:1235 The upregulated proteins in the EPS led to a decrease in the relative hydrophobicity of the sludge and an increase in negative surface charge. 35085842 5 32 theme filamentous 825:835 arg1 bacteria 837:844 filamentous bacteria 825:844 filamentous bacteria 825:844 Triggered QS by filamentous bacteria proliferation induced variation in the composition and structure of EPS within the sludge flocs. 35085842 15 33 theme filamentous 2275:2285 arg1 bulking 2287:2293 filamentous bulking 2275:2293 filamentous bulking 2275:2293 This study provides new information regarding the microcosmic mechanisms of filamentous bulking. 35085842 9 34 theme sludge 1573:1578 arg1 bulking 1580:1586 sludge bulking 1573:1586 sludge bulking 1573:1586 The total energy of the interaction (WT) between bacteria increased during sludge bulking, which resulted in the weakening of sludge aggregation. 35085842 2 35 theme filamentous 364:374 arg1 bulking 376:382 filamentous bulking 364:382 filamentous bulking 364:382 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 11 36 from expression 1866:1875 arg1 EPS 1854:1856 the EPS 1850:1856 the EPS 1850:1856 The production of PN in the EPS and the expression of the hdtS gene were inhibited by vanillin, which served as a QS inhibitor. 35085842 10 37 theme EPS 1691:1693 arg1 properties 1677:1686 the physicochemical properties 1657:1686 the physicochemical properties of EPS induced by QS in the filamentous bacteria 1657:1735 Variation in the physicochemical properties of EPS induced by QS in the filamentous bacteria markedly restrained adhesion between the filamentous bacteria and floc-forming bacteria. 35085842 6 38 theme polysaccharides 1062:1076 arg1 content 1083:1089 the polysaccharides (PS) content 1058:1089 the polysaccharides (PS) content 1058:1089 The proteins (PN) content of the EPS increased evidently from 40.06 ± 2.41 mg/g VSS to 110.32 ± 4.32 mg/g VSS, and the polysaccharides (PS) content slightly increased during filamentous bulking. 35085842 14 39 dep prevention 2152:2161 arg1 the 2148:2150 the 2148:2150 the 2148:2150 Therefore, QQ is a potential strategy for the prevention and control of filamentous bulking. 35085842 2 40 theme quorum 413:418 arg1 QQ 431:432 QQ 431:432 QQ 431:432 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 2 40 theme quorum 413:418 arg1 quenching 420:428 quorum quenching 413:428 quorum quenching (QQ) 413:433 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 0 41 theme sludge 29:34 arg1 bulking 36:42 filamentous sludge bulking 17:42 filamentous sludge bulking 17:42 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 35085842 10 42 from Variation 1644:1652 arg1 properties 1677:1686 the physicochemical properties 1657:1686 the physicochemical properties of EPS induced by QS in the filamentous bacteria 1657:1735 Variation in the physicochemical properties of EPS induced by QS in the filamentous bacteria markedly restrained adhesion between the filamentous bacteria and floc-forming bacteria. 35085842 2 43 theme floc 454:457 arg1 stability 459:467 sludge floc stability 447:467 sludge floc stability 447:467 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 5 44 dep composition 885:895 arg1 the 881:883 the 881:883 the 881:883 Triggered QS by filamentous bacteria proliferation induced variation in the composition and structure of EPS within the sludge flocs. 35085842 7 45 from proteins 1154:1161 arg1 EPS 1170:1172 the EPS 1166:1172 the EPS 1166:1172 The upregulated proteins in the EPS led to a decrease in the relative hydrophobicity of the sludge and an increase in negative surface charge. 35085842 2 46 theme floc 328:331 arg1 stability 333:341 sludge floc stability 321:341 sludge floc stability 321:341 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 6 47 theme filamentous 1117:1127 arg1 bulking 1129:1135 filamentous bulking 1117:1135 filamentous bulking 1117:1135 The proteins (PN) content of the EPS increased evidently from 40.06 ± 2.41 mg/g VSS to 110.32 ± 4.32 mg/g VSS, and the polysaccharides (PS) content slightly increased during filamentous bulking. 35085842 11 48 theme hdtS 1884:1887 arg1 gene 1889:1892 the hdtS gene 1880:1892 the hdtS gene 1880:1892 The production of PN in the EPS and the expression of the hdtS gene were inhibited by vanillin, which served as a QS inhibitor. 35085842 0 49 theme Potential 45:53 arg1 role 55:58 Potential role 45:58 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 0:143 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 35085842 6 50 theme proteins 947:954 arg1 content 961:967 The proteins (PN) content 943:967 The proteins (PN) content of the EPS 943:978 The proteins (PN) content of the EPS increased evidently from 40.06 ± 2.41 mg/g VSS to 110.32 ± 4.32 mg/g VSS, and the polysaccharides (PS) content slightly increased during filamentous bulking. 35085842 9 51 theme aggregation 1631:1641 arg1 weakening 1611:1619 the weakening 1607:1619 the weakening of sludge aggregation 1607:1641 The total energy of the interaction (WT) between bacteria increased during sludge bulking, which resulted in the weakening of sludge aggregation. 35085842 7 52 theme surface 1265:1271 arg1 charge 1273:1278 negative surface charge 1256:1278 negative surface charge 1256:1278 The upregulated proteins in the EPS led to a decrease in the relative hydrophobicity of the sludge and an increase in negative surface charge. 35085842 7 53 theme upregulated 1142:1152 arg1 proteins 1154:1161 The upregulated proteins 1138:1161 The upregulated proteins in the EPS 1138:1172 The upregulated proteins in the EPS led to a decrease in the relative hydrophobicity of the sludge and an increase in negative surface charge. 35085842 10 54 theme filamentous 1716:1726 arg1 bacteria 1728:1735 the filamentous bacteria 1712:1735 the filamentous bacteria 1712:1735 Variation in the physicochemical properties of EPS induced by QS in the filamentous bacteria markedly restrained adhesion between the filamentous bacteria and floc-forming bacteria. 35085842 7 55 from increase 1244:1251 arg1 hydrophobicity 1208:1221 the relative hydrophobicity 1195:1221 the relative hydrophobicity of the sludge 1195:1235 The upregulated proteins in the EPS led to a decrease in the relative hydrophobicity of the sludge and an increase in negative surface charge. 35085842 7 55 from increase 1244:1251 arg1 charge 1273:1278 negative surface charge 1256:1278 negative surface charge 1256:1278 The upregulated proteins in the EPS led to a decrease in the relative hydrophobicity of the sludge and an increase in negative surface charge. 35085842 14 56 theme filamentous 2178:2188 arg1 bulking 2190:2196 filamentous bulking 2178:2196 filamentous bulking 2178:2196 Therefore, QQ is a potential strategy for the prevention and control of filamentous bulking. 35085842 2 57 theme quorum 284:289 arg1 sensing 291:297 quorum sensing 284:297 quorum sensing (QS) 284:302 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 2 57 theme quorum 284:289 arg1 QS 300:301 QS 300:301 QS 300:301 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 7 58 theme sludge 1230:1235 arg1 hydrophobicity 1208:1221 the relative hydrophobicity 1195:1221 the relative hydrophobicity of the sludge 1195:1235 The upregulated proteins in the EPS led to a decrease in the relative hydrophobicity of the sludge and an increase in negative surface charge. 35085842 10 59 theme floc-forming 1803:1814 arg1 bacteria 1816:1823 floc-forming bacteria 1803:1823 floc-forming bacteria 1803:1823 Variation in the physicochemical properties of EPS induced by QS in the filamentous bacteria markedly restrained adhesion between the filamentous bacteria and floc-forming bacteria. 35085842 11 60 from production 1830:1839 arg1 EPS 1854:1856 the EPS 1850:1856 the EPS 1850:1856 The production of PN in the EPS and the expression of the hdtS gene were inhibited by vanillin, which served as a QS inhibitor. 35085842 4 61 theme filamentous 680:690 arg1 bacteria 692:699 The filamentous bacteria 676:699 The filamentous bacteria 676:699 The filamentous bacteria gradually evolved the hdtS gene related to the synthesis of C6HSL with increases in the population density. 35085842 2 62 theme substances 255:264 arg1 sludge 487:492 sludge settling 487:501 sludge settling 487:501 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 2 62 theme substances 255:264 arg1 structure 473:481 structure 473:481 structure 473:481 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 2 62 theme substances 255:264 arg1 role 223:226 The role 219:226 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability 219:467 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 14 63 theme potential 2125:2133 arg1 strategy 2135:2142 a potential strategy 2123:2142 a potential strategy for the prevention and control of filamentous bulking 2123:2196 Therefore, QQ is a potential strategy for the prevention and control of filamentous bulking. 35085842 14 63 theme potential 2125:2133 arg1 QQ 2117:2118 QQ 2117:2118 QQ 2117:2118 Therefore, QQ is a potential strategy for the prevention and control of filamentous bulking. 35085842 4 64 with C6HSL 761:765 arg1 increases 772:780 increases 772:780 increases in the population density 772:806 The filamentous bacteria gradually evolved the hdtS gene related to the synthesis of C6HSL with increases in the population density. 35085842 2 65 theme extracellular 231:243 arg1 EPS 267:269 EPS 267:269 EPS 267:269 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 2 65 theme extracellular 231:243 arg1 substances 255:264 extracellular polymeric substances 231:264 extracellular polymeric substances (EPS) governed by quorum sensing (QS) 231:302 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 8 66 theme hydrophobic 1478:1488 arg1 groups 1490:1495 inner hydrophobic groups 1472:1495 inner hydrophobic groups 1472:1495 The α-helix/(β-sheet+random coil) ratio evidently increased from 0.76 to 0.99 during filamentous bulking, revealing that the proteins were tightly structured, which prevented the exposure of inner hydrophobic groups. 35085842 11 67 theme PN 1844:1845 arg1 production 1830:1839 The production 1826:1839 The production of PN in the EPS 1826:1856 The production of PN in the EPS and the expression of the hdtS gene were inhibited by vanillin, which served as a QS inhibitor. 35085842 11 67 theme PN 1844:1845 arg1 expression 1866:1875 the expression 1862:1875 the expression of the hdtS gene 1862:1892 The production of PN in the EPS and the expression of the hdtS gene were inhibited by vanillin, which served as a QS inhibitor. 35085842 5 68 from variation 868:876 arg1 structure 901:909 structure 901:909 structure 901:909 Triggered QS by filamentous bacteria proliferation induced variation in the composition and structure of EPS within the sludge flocs. 35085842 5 68 from variation 868:876 arg1 composition 885:895 composition 885:895 composition 885:895 Triggered QS by filamentous bacteria proliferation induced variation in the composition and structure of EPS within the sludge flocs. 35085842 8 69 theme coil 1309:1312 arg1 ratio 1315:1319 The α-helix/(β-sheet+random coil) ratio 1281:1319 The α-helix/(β-sheet+random coil) ratio 1281:1319 The α-helix/(β-sheet+random coil) ratio evidently increased from 0.76 to 0.99 during filamentous bulking, revealing that the proteins were tightly structured, which prevented the exposure of inner hydrophobic groups. 35085842 3 70 theme 22.08±3.22 ng/g 605:619 arg1 VSS 621:623 22.08±3.22 ng/g VSS 605:623 22.08±3.22 ng/g VSS 605:623 The results indicated that the concentration of C6HSL increased from 22.08±3.22 ng/g VSS to 81.42±5.98 ng/g VSS during filamentous bulking. 35085842 5 71 theme EPS 914:916 arg1 structure 901:909 structure 901:909 structure 901:909 Triggered QS by filamentous bacteria proliferation induced variation in the composition and structure of EPS within the sludge flocs. 35085842 5 71 theme EPS 914:916 arg1 composition 885:895 composition 885:895 composition 885:895 Triggered QS by filamentous bacteria proliferation induced variation in the composition and structure of EPS within the sludge flocs. 35085842 6 72 theme 110.32 ± 4.32 mg/g 1030:1047 arg1 VSS 1049:1051 110.32 ± 4.32 mg/g VSS 1030:1051 110.32 ± 4.32 mg/g VSS 1030:1051 The proteins (PN) content of the EPS increased evidently from 40.06 ± 2.41 mg/g VSS to 110.32 ± 4.32 mg/g VSS, and the polysaccharides (PS) content slightly increased during filamentous bulking. 35085842 0 73 theme quorum 76:81 arg1 sensing 83:89 AHL-mediated quorum sensing 63:89 AHL-mediated quorum sensing 63:89 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 35085842 1 74 theme microcosmic 149:159 arg1 mechanisms 161:170 The microcosmic mechanisms 145:170 The microcosmic mechanisms underlying filamentous bulking 145:201 The microcosmic mechanisms underlying filamentous bulking remain unclear. 35085842 0 75 theme sludge 108:113 arg1 stability 120:128 sludge floc stability 108:128 sludge floc stability 108:128 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 35085842 13 76 theme Filamentous 2029:2039 arg1 bulking 2041:2047 Filamentous bulking 2029:2047 Filamentous bulking 2029:2047 Filamentous bulking was significantly inhibited by the addition of vanillin. 35085842 4 77 from increases 772:780 arg1 density 800:806 the population density 785:806 the population density 785:806 The filamentous bacteria gradually evolved the hdtS gene related to the synthesis of C6HSL with increases in the population density. 35085842 7 78 from decrease 1183:1190 arg1 hydrophobicity 1208:1221 the relative hydrophobicity 1195:1221 the relative hydrophobicity of the sludge 1195:1235 The upregulated proteins in the EPS led to a decrease in the relative hydrophobicity of the sludge and an increase in negative surface charge. 35085842 7 78 from decrease 1183:1190 arg1 charge 1273:1278 negative surface charge 1256:1278 negative surface charge 1256:1278 The upregulated proteins in the EPS led to a decrease in the relative hydrophobicity of the sludge and an increase in negative surface charge. 35085842 8 79 theme filamentous 1366:1376 arg1 bulking 1378:1384 filamentous bulking 1366:1384 filamentous bulking 1366:1384 The α-helix/(β-sheet+random coil) ratio evidently increased from 0.76 to 0.99 during filamentous bulking, revealing that the proteins were tightly structured, which prevented the exposure of inner hydrophobic groups. 35085842 0 80 theme filamentous 17:27 arg1 bulking 36:42 filamentous sludge bulking 17:42 filamentous sludge bulking 17:42 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 35085842 0 81 dep insight 4:10 arg1 role 55:58 Potential role 45:58 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 0:143 New insight into filamentous sludge bulking: Potential role of AHL-mediated quorum sensing in deteriorating sludge floc stability and structure. 35085842 3 82 theme filamentous 655:665 arg1 bulking 667:673 filamentous bulking 655:673 filamentous bulking 655:673 The results indicated that the concentration of C6HSL increased from 22.08±3.22 ng/g VSS to 81.42±5.98 ng/g VSS during filamentous bulking. 35085842 4 83 theme C6HSL 761:765 arg1 synthesis 748:756 the synthesis 744:756 the synthesis of C6HSL with increases in the population density 744:806 The filamentous bacteria gradually evolved the hdtS gene related to the synthesis of C6HSL with increases in the population density. 35085842 10 84 theme physicochemical 1661:1675 arg1 properties 1677:1686 the physicochemical properties 1657:1686 the physicochemical properties of EPS induced by QS in the filamentous bacteria 1657:1735 Variation in the physicochemical properties of EPS induced by QS in the filamentous bacteria markedly restrained adhesion between the filamentous bacteria and floc-forming bacteria. 35085842 5 85 theme Triggered 809:817 arg1 proliferation 846:858 Triggered QS by filamentous bacteria proliferation 809:858 Triggered QS by filamentous bacteria proliferation 809:858 Triggered QS by filamentous bacteria proliferation induced variation in the composition and structure of EPS within the sludge flocs. 35085842 15 86 theme microcosmic 2249:2259 arg1 mechanisms 2261:2270 the microcosmic mechanisms 2245:2270 the microcosmic mechanisms of filamentous bulking 2245:2293 This study provides new information regarding the microcosmic mechanisms of filamentous bulking. 35085842 2 87 theme sludge 447:452 arg1 stability 459:467 sludge floc stability 447:467 sludge floc stability 447:467 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 2 88 theme sludge 321:326 arg1 stability 333:341 sludge floc stability 321:341 sludge floc stability 321:341 The role of extracellular polymeric substances (EPS) governed by quorum sensing (QS) in deteriorating sludge floc stability and structure during filamentous bulking and the feasibility of using quorum quenching (QQ) to maintain sludge floc stability and structure and sludge settling were investigated in this study. 35085842 9 89 theme sludge 1624:1629 arg1 aggregation 1631:1641 sludge aggregation 1624:1641 sludge aggregation 1624:1641 The total energy of the interaction (WT) between bacteria increased during sludge bulking, which resulted in the weakening of sludge aggregation. 35085842 7 90 theme negative 1256:1263 arg1 charge 1273:1278 negative surface charge 1256:1278 negative surface charge 1256:1278 The upregulated proteins in the EPS led to a decrease in the relative hydrophobicity of the sludge and an increase in negative surface charge. 35085842 11 91 theme gene 1889:1892 arg1 production 1830:1839 The production 1826:1839 The production of PN in the EPS 1826:1856 The production of PN in the EPS and the expression of the hdtS gene were inhibited by vanillin, which served as a QS inhibitor. 35085842 11 91 theme gene 1889:1892 arg1 expression 1866:1875 the expression 1862:1875 the expression of the hdtS gene 1862:1892 The production of PN in the EPS and the expression of the hdtS gene were inhibited by vanillin, which served as a QS inhibitor. 37279383 7 0 theme higher 1101:1106 arg1 effect 1120:1125 the higher conjugation effect 1097:1125 the higher conjugation effect 1097:1125 Due to the higher conjugation effect and lower HOMO-LUMO energy difference, TNB could be used as a supercapacitor electrode. 37279383 10 1 theme % 1637:1637 arg1 stability 1646:1654 ∼96% cyclic stability 1634:1654 ∼96% cyclic stability 1634:1654 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 9 2 theme aqueous 1381:1387 arg1 electrolyte 1389:1399 an aqueous electrolyte 1378:1399 an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g 1378:1479 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 2 3 theme oxazaborinine 340:352 arg1 TNB 365:367 TNB 365:367 TNB (a tri-naphthalene boron complex) 365:401 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 3 theme oxazaborinine 340:352 arg1 complexes 354:362 Two oxazaborinine complexes 336:362 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine 336:489 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 3 theme oxazaborinine 340:352 arg1 DNB 407:409 DNB 407:409 DNB (a di-naphthalene boron complex) 407:442 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 1 4 theme organic 147:153 arg1 emitter 155:161 Developing a solid organic emitter 128:161 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics 128:239 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics has become essential to fulfilling the rising need for optical and electrochemical technology. 37279383 1 5 theme photophysical 211:223 arg1 characteristics 225:239 improved photophysical characteristics 202:239 improved photophysical characteristics 202:239 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics has become essential to fulfilling the rising need for optical and electrochemical technology. 37279383 11 6 from efficiency 1736:1745 arg1 electrolytes 1758:1769 aqueous electrolytes 1750:1769 aqueous electrolytes 1750:1769 The reported oxazaborinine complex and its electrochemical efficiency in aqueous electrolytes make it ideal for supercapacitor applications and directly impact the development of advanced electrodes for next-generation supercapacitors. 37279383 8 7 theme three-electrode 1220:1234 arg1 configuration 1236:1248 a three-electrode configuration 1218:1248 a three-electrode configuration 1218:1248 In a three-electrode configuration, TNB has a maximum specific capacitance of 896.25 F/g. 37279383 10 8 theme potential 1551:1559 arg1 window 1561:1566 the operating potential window 1537:1566 the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability 1537:1654 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 3 9 theme supercapacitor 610:623 arg1 electrodes 625:634 asymmetric supercapacitor electrodes 599:634 asymmetric supercapacitor electrodes in aqueous electrolytes 599:658 Their effectiveness as asymmetric supercapacitor electrodes in aqueous electrolytes is also being studied. 37279383 9 10 theme positive 1416:1423 arg1 TNB 1407:1409 TNB 1407:1409 TNB 1407:1409 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 9 10 theme positive 1416:1423 arg1 electrode 1425:1433 a positive electrode 1414:1433 a positive electrode having a high specific capacitance of 155 F/g 1414:1479 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 4 11 theme Polynapthaldimine-substituted 683:711 arg1 DNI 713:715 Polynapthaldimine-substituted DNI 683:715 Polynapthaldimine-substituted DNI (di-naphthalene imine) 683:738 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 4 11 theme Polynapthaldimine-substituted 683:711 arg1 imine 733:737 di-naphthalene imine 718:737 di-naphthalene imine 718:737 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 5 12 theme red 945:947 arg1 light 949:953 pure red light 940:953 pure red light 940:953 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 11 13 from complex 1704:1710 arg1 electrolytes 1758:1769 aqueous electrolytes 1750:1769 aqueous electrolytes 1750:1769 The reported oxazaborinine complex and its electrochemical efficiency in aqueous electrolytes make it ideal for supercapacitor applications and directly impact the development of advanced electrodes for next-generation supercapacitors. 37279383 2 14 from emission 523:530 arg1 region 549:554 the red light region 535:554 the red light region 535:554 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 14 from emission 523:530 arg1 phase 569:573 the solid phase 559:573 the solid phase 559:573 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 10 15 theme V 1580:1580 arg1 window 1561:1566 the operating potential window 1537:1566 the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability 1537:1654 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 9 16 theme high 1444:1447 arg1 capacitance 1458:1468 a high specific capacitance 1442:1468 a high specific capacitance of 155 F/g 1442:1479 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 8 17 theme maximum 1261:1267 arg1 capacitance 1278:1288 a maximum specific capacitance 1259:1288 a maximum specific capacitance of 896.25 F/g 1259:1302 In a three-electrode configuration, TNB has a maximum specific capacitance of 896.25 F/g. 37279383 11 18 theme aqueous 1750:1756 arg1 electrolytes 1758:1769 aqueous electrolytes 1750:1769 aqueous electrolytes 1750:1769 The reported oxazaborinine complex and its electrochemical efficiency in aqueous electrolytes make it ideal for supercapacitor applications and directly impact the development of advanced electrodes for next-generation supercapacitors. 37279383 2 19 theme red 539:541 arg1 region 549:554 the red light region 535:554 the red light region 535:554 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 5 20 theme λem 864:866 arg1 solids 856:861 solids 856:861 solids (λem 660 nm) 856:874 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 5 20 theme λem 864:866 arg1 nm 872:873 λem 660 nm 864:873 λem 660 nm 864:873 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 1 21 theme oxazaborinine 175:187 arg1 complex 189:195 an oxazaborinine complex 172:195 an oxazaborinine complex with improved photophysical characteristics 172:239 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics has become essential to fulfilling the rising need for optical and electrochemical technology. 37279383 2 22 dep complexes 354:362 arg1 complex 394:400 a tri-naphthalene boron complex 370:400 a tri-naphthalene boron complex 370:400 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 22 dep complexes 354:362 arg1 TNB 365:367 TNB 365:367 TNB (a tri-naphthalene boron complex) 365:401 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 22 dep complexes 354:362 arg1 complex 435:441 a di-naphthalene boron complex 412:441 a di-naphthalene boron complex 412:441 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 22 dep complexes 354:362 arg1 complexes 354:362 Two oxazaborinine complexes 336:362 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine 336:489 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 22 dep complexes 354:362 arg1 DNB 407:409 DNB 407:409 DNB (a di-naphthalene boron complex) 407:442 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 0 23 theme Asymmetric 100:109 arg1 Supercapacitors 111:125 High-Performance Asymmetric Supercapacitors 83:125 High-Performance Asymmetric Supercapacitors 83:125 Polynaphthalene-Based Oxazaborinine Complexes Formulated as Red Light Emitters and High-Performance Asymmetric Supercapacitors. 37279383 5 24 theme λem 923:925 arg1 nm 931:932 λem 632 nm 923:932 λem 632 nm 923:932 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 5 24 theme λem 923:925 arg1 composite 912:920 the polydimethylsiloxane (PDMS) composite 880:920 the polydimethylsiloxane (PDMS) composite (λem 632 nm) 880:933 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 11 25 theme reported 1681:1688 arg1 complex 1704:1710 The reported oxazaborinine complex 1677:1710 The reported oxazaborinine complex 1677:1710 The reported oxazaborinine complex and its electrochemical efficiency in aqueous electrolytes make it ideal for supercapacitor applications and directly impact the development of advanced electrodes for next-generation supercapacitors. 37279383 4 26 theme O-linked 825:832 arg1 N 823:823 a N 821:823 a N 821:823 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 4 26 theme O-linked 825:832 arg1 complex 840:846 O-linked boron complex 825:846 O-linked boron complex 825:846 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 10 27 theme enhanced 1590:1597 arg1 density 1606:1612 an enhanced energy density 1587:1612 an enhanced energy density of 42.19 W h/kg 1587:1628 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 2 28 theme tri-naphthalene 372:386 arg1 complex 394:400 a tri-naphthalene boron complex 370:400 a tri-naphthalene boron complex 370:400 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 28 theme tri-naphthalene 372:386 arg1 TNB 365:367 TNB 365:367 TNB (a tri-naphthalene boron complex) 365:401 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 6 29 theme functional 1065:1074 arg1 DFT 1084:1086 DFT 1084:1086 DFT 1084:1086 The optimized structure has been generated, and the HOMO-LUMO energy was calculated with the help of density functional theory (DFT). 37279383 6 29 theme functional 1065:1074 arg1 theory 1076:1081 density functional theory 1057:1081 density functional theory (DFT) 1057:1087 The optimized structure has been generated, and the HOMO-LUMO energy was calculated with the help of density functional theory (DFT). 37279383 9 30 contain having 1435:1440 arg1 TNB 1407:1409 TNB 1407:1409 TNB 1407:1409 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 9 30 contain having 1435:1440 arg2 capacitance 1458:1468 a high specific capacitance 1442:1468 a high specific capacitance of 155 F/g 1442:1479 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 9 30 contain having 1435:1440 arg1 electrode 1425:1433 a positive electrode 1414:1433 a positive electrode having a high specific capacitance of 155 F/g 1414:1479 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 7 31 theme supercapacitor 1189:1202 arg1 TNB 1166:1168 TNB 1166:1168 TNB 1166:1168 Due to the higher conjugation effect and lower HOMO-LUMO energy difference, TNB could be used as a supercapacitor electrode. 37279383 7 31 theme supercapacitor 1189:1202 arg1 electrode 1204:1212 a supercapacitor electrode 1187:1212 a supercapacitor electrode 1187:1212 Due to the higher conjugation effect and lower HOMO-LUMO energy difference, TNB could be used as a supercapacitor electrode. 37279383 2 32 theme boron 429:433 arg1 complex 435:441 a di-naphthalene boron complex 412:441 a di-naphthalene boron complex 412:441 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 32 theme boron 429:433 arg1 DNB 407:409 DNB 407:409 DNB (a di-naphthalene boron complex) 407:442 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 0 33 theme Polynaphthalene-Based 0:20 arg1 Complexes 36:44 Polynaphthalene-Based Oxazaborinine Complexes 0:44 Polynaphthalene-Based Oxazaborinine Complexes 0:44 Polynaphthalene-Based Oxazaborinine Complexes Formulated as Red Light Emitters and High-Performance Asymmetric Supercapacitors. 37279383 1 34 theme Developing 128:137 arg1 emitter 155:161 Developing a solid organic emitter 128:161 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics 128:239 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics has become essential to fulfilling the rising need for optical and electrochemical technology. 37279383 10 35 theme 42.19 1617:1621 arg1 h/kg 1625:1628 42.19 W h/kg 1617:1628 42.19 W h/kg 1617:1628 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 7 36 theme energy 1147:1152 arg1 difference 1154:1163 lower HOMO-LUMO energy difference 1131:1163 lower HOMO-LUMO energy difference 1131:1163 Due to the higher conjugation effect and lower HOMO-LUMO energy difference, TNB could be used as a supercapacitor electrode. 37279383 1 37 theme solid 141:145 arg1 emitter 155:161 Developing a solid organic emitter 128:161 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics 128:239 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics has become essential to fulfilling the rising need for optical and electrochemical technology. 37279383 7 38 theme lower 1131:1135 arg1 difference 1154:1163 lower HOMO-LUMO energy difference 1131:1163 lower HOMO-LUMO energy difference 1131:1163 Due to the higher conjugation effect and lower HOMO-LUMO energy difference, TNB could be used as a supercapacitor electrode. 37279383 9 39 theme supercapacitor 1332:1345 arg1 device 1347:1352 an asymmetric supercapacitor device 1318:1352 an asymmetric supercapacitor device (ASC) 1318:1358 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 9 39 theme supercapacitor 1332:1345 arg1 ASC 1355:1357 ASC 1355:1357 ASC 1355:1357 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 10 40 theme ∼96 1634:1636 arg1 % 1637:1637 % 1637:1637 % 1637:1637 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 0 41 theme Light 64:68 arg1 Emitters 70:77 Red Light Emitters 60:77 Red Light Emitters 60:77 Polynaphthalene-Based Oxazaborinine Complexes Formulated as Red Light Emitters and High-Performance Asymmetric Supercapacitors. 37279383 10 42 with window 1561:1566 arg1 density 1606:1612 an enhanced energy density 1587:1612 an enhanced energy density of 42.19 W h/kg 1587:1628 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 10 42 with window 1561:1566 arg1 stability 1646:1654 ∼96% cyclic stability 1634:1654 ∼96% cyclic stability 1634:1654 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 2 43 theme boron 388:392 arg1 complex 394:400 a tri-naphthalene boron complex 370:400 a tri-naphthalene boron complex 370:400 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 43 theme boron 388:392 arg1 TNB 365:367 TNB 365:367 TNB (a tri-naphthalene boron complex) 365:401 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 11 44 theme next-generation 1880:1894 arg1 supercapacitors 1896:1910 next-generation supercapacitors 1880:1910 next-generation supercapacitors 1880:1910 The reported oxazaborinine complex and its electrochemical efficiency in aqueous electrolytes make it ideal for supercapacitor applications and directly impact the development of advanced electrodes for next-generation supercapacitors. 37279383 5 45 theme polydimethylsiloxane 884:903 arg1 nm 931:932 λem 632 nm 923:932 λem 632 nm 923:932 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 5 45 theme polydimethylsiloxane 884:903 arg1 composite 912:920 the polydimethylsiloxane (PDMS) composite 880:920 the polydimethylsiloxane (PDMS) composite (λem 632 nm) 880:933 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 10 46 theme aqueous 1493:1499 arg1 electrolyte 1501:1511 an aqueous electrolyte 1490:1511 an aqueous electrolyte 1490:1511 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 10 47 theme cyclic 1639:1644 arg1 stability 1646:1654 ∼96% cyclic stability 1634:1654 ∼96% cyclic stability 1634:1654 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 1 48 theme optical 296:302 arg1 technology 324:333 optical and electrochemical technology 296:333 optical and electrochemical technology 296:333 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics has become essential to fulfilling the rising need for optical and electrochemical technology. 37279383 8 49 contain has 1255:1257 arg2 capacitance 1278:1288 a maximum specific capacitance 1259:1288 a maximum specific capacitance of 896.25 F/g 1259:1302 In a three-electrode configuration, TNB has a maximum specific capacitance of 896.25 F/g. 37279383 8 49 contain has 1255:1257 arg1 TNB 1251:1253 TNB 1251:1253 TNB 1251:1253 In a three-electrode configuration, TNB has a maximum specific capacitance of 896.25 F/g. 37279383 1 50 theme electrochemical 308:322 arg1 technology 324:333 optical and electrochemical technology 296:333 optical and electrochemical technology 296:333 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics has become essential to fulfilling the rising need for optical and electrochemical technology. 37279383 10 51 theme ASC 1518:1520 arg1 device 1522:1527 the ASC device 1514:1527 the ASC device 1514:1527 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 11 52 theme supercapacitor 1789:1802 arg1 applications 1804:1815 supercapacitor applications 1789:1815 supercapacitor applications 1789:1815 The reported oxazaborinine complex and its electrochemical efficiency in aqueous electrolytes make it ideal for supercapacitor applications and directly impact the development of advanced electrodes for next-generation supercapacitors. 37279383 1 53 theme improved 202:209 arg1 characteristics 225:239 improved photophysical characteristics 202:239 improved photophysical characteristics 202:239 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics has become essential to fulfilling the rising need for optical and electrochemical technology. 37279383 4 54 theme di-naphthalene 718:731 arg1 DNI 713:715 Polynapthaldimine-substituted DNI 683:715 Polynapthaldimine-substituted DNI (di-naphthalene imine) 683:738 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 4 54 theme di-naphthalene 718:731 arg1 imine 733:737 di-naphthalene imine 718:737 di-naphthalene imine 718:737 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 3 55 theme asymmetric 599:608 arg1 electrodes 625:634 asymmetric supercapacitor electrodes 599:634 asymmetric supercapacitor electrodes in aqueous electrolytes 599:658 Their effectiveness as asymmetric supercapacitor electrodes in aqueous electrolytes is also being studied. 37279383 10 56 theme operating 1541:1549 arg1 window 1561:1566 the operating potential window 1537:1566 the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability 1537:1654 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 6 57 theme optimized 960:968 arg1 structure 970:978 The optimized structure 956:978 The optimized structure 956:978 The optimized structure has been generated, and the HOMO-LUMO energy was calculated with the help of density functional theory (DFT). 37279383 8 58 theme F/g 1300:1302 arg1 capacitance 1278:1288 a maximum specific capacitance 1259:1288 a maximum specific capacitance of 896.25 F/g 1259:1302 In a three-electrode configuration, TNB has a maximum specific capacitance of 896.25 F/g. 37279383 11 59 theme electrochemical 1720:1734 arg1 efficiency 1736:1745 its electrochemical efficiency 1716:1745 its electrochemical efficiency in aqueous electrolytes 1716:1769 The reported oxazaborinine complex and its electrochemical efficiency in aqueous electrolytes make it ideal for supercapacitor applications and directly impact the development of advanced electrodes for next-generation supercapacitors. 37279383 3 60 theme aqueous 639:645 arg1 electrolytes 647:658 aqueous electrolytes 639:658 aqueous electrolytes 639:658 Their effectiveness as asymmetric supercapacitor electrodes in aqueous electrolytes is also being studied. 37279383 5 61 theme PDMS 906:909 arg1 nm 931:932 λem 632 nm 923:932 λem 632 nm 923:932 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 5 61 theme PDMS 906:909 arg1 composite 912:920 the polydimethylsiloxane (PDMS) composite 880:920 the polydimethylsiloxane (PDMS) composite (λem 632 nm) 880:933 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 2 62 theme solid 563:567 arg1 phase 569:573 the solid phase 559:573 the solid phase 559:573 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 9 63 theme specific 1449:1456 arg1 capacitance 1458:1468 a high specific capacitance 1442:1468 a high specific capacitance of 155 F/g 1442:1479 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 8 64 theme specific 1269:1276 arg1 capacitance 1278:1288 a maximum specific capacitance 1259:1288 a maximum specific capacitance of 896.25 F/g 1259:1302 In a three-electrode configuration, TNB has a maximum specific capacitance of 896.25 F/g. 37279383 10 65 theme h/kg 1625:1628 arg1 density 1606:1612 an enhanced energy density 1587:1612 an enhanced energy density of 42.19 W h/kg 1587:1628 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 10 65 theme h/kg 1625:1628 arg1 stability 1646:1654 ∼96% cyclic stability 1634:1654 ∼96% cyclic stability 1634:1654 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 0 66 theme High-Performance 83:98 arg1 Supercapacitors 111:125 High-Performance Asymmetric Supercapacitors 83:125 High-Performance Asymmetric Supercapacitors 83:125 Polynaphthalene-Based Oxazaborinine Complexes Formulated as Red Light Emitters and High-Performance Asymmetric Supercapacitors. 37279383 9 67 theme F/g 1477:1479 arg1 capacitance 1458:1468 a high specific capacitance 1442:1468 a high specific capacitance of 155 F/g 1442:1479 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 6 68 theme HOMO-LUMO 1008:1016 arg1 energy 1018:1023 the HOMO-LUMO energy 1004:1023 the HOMO-LUMO energy 1004:1023 The optimized structure has been generated, and the HOMO-LUMO energy was calculated with the help of density functional theory (DFT). 37279383 5 69 from TNB 849:851 arg1 solids 856:861 solids 856:861 solids (λem 660 nm) 856:874 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 5 69 from TNB 849:851 arg1 nm 872:873 λem 660 nm 864:873 λem 660 nm 864:873 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 1 70 with complex 189:195 arg1 characteristics 225:239 improved photophysical characteristics 202:239 improved photophysical characteristics 202:239 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics has become essential to fulfilling the rising need for optical and electrochemical technology. 37279383 4 71 theme tri-naphthalene 749:763 arg1 TNI 744:746 TNI 744:746 TNI (tri-naphthalene imine) 744:770 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 4 71 theme tri-naphthalene 749:763 arg1 imine 765:769 tri-naphthalene imine 749:769 tri-naphthalene imine 749:769 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 4 72 theme boron 834:838 arg1 N 823:823 a N 821:823 a N 821:823 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 4 72 theme boron 834:838 arg1 complex 840:846 O-linked boron complex 825:846 O-linked boron complex 825:846 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 11 73 theme oxazaborinine 1690:1702 arg1 complex 1704:1710 The reported oxazaborinine complex 1677:1710 The reported oxazaborinine complex 1677:1710 The reported oxazaborinine complex and its electrochemical efficiency in aqueous electrolytes make it ideal for supercapacitor applications and directly impact the development of advanced electrodes for next-generation supercapacitors. 37279383 5 74 from composite 912:920 arg1 solids 856:861 solids 856:861 solids (λem 660 nm) 856:874 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 5 74 from composite 912:920 arg1 nm 872:873 λem 660 nm 864:873 λem 660 nm 864:873 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 2 75 theme light 543:547 arg1 region 549:554 the red light region 535:554 the red light region 535:554 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 6 76 dep the 1045:1047 arg1 help 1049:1052 help 1049:1052 help 1049:1052 The optimized structure has been generated, and the HOMO-LUMO energy was calculated with the help of density functional theory (DFT). 37279383 11 77 theme electrodes 1865:1874 arg1 development 1841:1851 the development 1837:1851 the development of advanced electrodes for next-generation supercapacitors 1837:1910 The reported oxazaborinine complex and its electrochemical efficiency in aqueous electrolytes make it ideal for supercapacitor applications and directly impact the development of advanced electrodes for next-generation supercapacitors. 37279383 0 78 theme Oxazaborinine 22:34 arg1 Complexes 36:44 Polynaphthalene-Based Oxazaborinine Complexes 0:44 Polynaphthalene-Based Oxazaborinine Complexes 0:44 Polynaphthalene-Based Oxazaborinine Complexes Formulated as Red Light Emitters and High-Performance Asymmetric Supercapacitors. 37279383 7 79 used used 1179:1182 arg2 electrode 1204:1212 a supercapacitor electrode 1187:1212 a supercapacitor electrode 1187:1212 Due to the higher conjugation effect and lower HOMO-LUMO energy difference, TNB could be used as a supercapacitor electrode. 37279383 7 79 used used 1179:1182 arg2 TNB 1166:1168 TNB 1166:1168 TNB 1166:1168 Due to the higher conjugation effect and lower HOMO-LUMO energy difference, TNB could be used as a supercapacitor electrode. 37279383 5 80 theme pure 940:943 arg1 light 949:953 pure red light 940:953 pure red light 940:953 TNB in solids (λem 660 nm) and the polydimethylsiloxane (PDMS) composite (λem 632 nm) emit pure red light. 37279383 6 81 theme density 1057:1063 arg1 DFT 1084:1086 DFT 1084:1086 DFT 1084:1086 The optimized structure has been generated, and the HOMO-LUMO energy was calculated with the help of density functional theory (DFT). 37279383 6 81 theme density 1057:1063 arg1 theory 1076:1081 density functional theory 1057:1081 density functional theory (DFT) 1057:1087 The optimized structure has been generated, and the HOMO-LUMO energy was calculated with the help of density functional theory (DFT). 37279383 3 82 from electrodes 625:634 arg1 electrolytes 647:658 aqueous electrolytes 639:658 aqueous electrolytes 639:658 Their effectiveness as asymmetric supercapacitor electrodes in aqueous electrolytes is also being studied. 37279383 2 83 theme di-naphthalene 414:427 arg1 complex 435:441 a di-naphthalene boron complex 412:441 a di-naphthalene boron complex 412:441 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 2 83 theme di-naphthalene 414:427 arg1 DNB 407:409 DNB 407:409 DNB (a di-naphthalene boron complex) 407:442 Two oxazaborinine complexes (TNB (a tri-naphthalene boron complex) and DNB (a di-naphthalene boron complex)) decorated with naphthalene and triphenylamine have been developed, which show emission in the red light region in the solid phase. 37279383 7 84 theme HOMO-LUMO 1137:1145 arg1 difference 1154:1163 lower HOMO-LUMO energy difference 1131:1163 lower HOMO-LUMO energy difference 1131:1163 Due to the higher conjugation effect and lower HOMO-LUMO energy difference, TNB could be used as a supercapacitor electrode. 37279383 0 85 theme Red 60:62 arg1 Emitters 70:77 Red Light Emitters 60:77 Red Light Emitters 60:77 Polynaphthalene-Based Oxazaborinine Complexes Formulated as Red Light Emitters and High-Performance Asymmetric Supercapacitors. 37279383 9 86 theme asymmetric 1321:1330 arg1 device 1347:1352 an asymmetric supercapacitor device 1318:1352 an asymmetric supercapacitor device (ASC) 1318:1358 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 9 86 theme asymmetric 1321:1330 arg1 ASC 1355:1357 ASC 1355:1357 ASC 1355:1357 Furthermore, an asymmetric supercapacitor device (ASC) was fabricated in an aqueous electrolyte using TNB as a positive electrode having a high specific capacitance of 155 F/g. 37279383 11 87 theme advanced 1856:1863 arg1 electrodes 1865:1874 advanced electrodes 1856:1874 advanced electrodes for next-generation supercapacitors 1856:1910 The reported oxazaborinine complex and its electrochemical efficiency in aqueous electrolytes make it ideal for supercapacitor applications and directly impact the development of advanced electrodes for next-generation supercapacitors. 37279383 10 88 theme energy 1599:1604 arg1 density 1606:1612 an enhanced energy density 1587:1612 an enhanced energy density of 42.19 W h/kg 1587:1628 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 7 89 theme conjugation 1108:1118 arg1 effect 1120:1125 the higher conjugation effect 1097:1125 the higher conjugation effect 1097:1125 Due to the higher conjugation effect and lower HOMO-LUMO energy difference, TNB could be used as a supercapacitor electrode. 37279383 4 90 link O-linked 825:832 arg1 N 823:823 a N 821:823 a N 821:823 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 4 90 link O-linked 825:832 arg1 complex 840:846 O-linked boron complex 825:846 O-linked boron complex 825:846 Polynapthaldimine-substituted DNI (di-naphthalene imine) and TNI (tri-naphthalene imine) have been initially synthesized and converted to a N,O-linked boron complex. 37279383 10 91 dep V 1580:1580 arg1 to 1573:1574 to 1573:1574 to 1573:1574 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 10 92 theme W 1623:1623 arg1 h/kg 1625:1628 42.19 W h/kg 1617:1628 42.19 W h/kg 1617:1628 Even in an aqueous electrolyte, the ASC device reached the operating potential window of 0 to 1.4 V with an enhanced energy density of 42.19 W h/kg and ∼96% cyclic stability after 10 000 cycles. 37279383 1 93 theme rising 280:285 arg1 need 287:290 the rising need 276:290 the rising need for optical and electrochemical technology 276:333 Developing a solid organic emitter based on an oxazaborinine complex with improved photophysical characteristics has become essential to fulfilling the rising need for optical and electrochemical technology. 35723049 7 0 theme downstream 978:987 arg1 targets 989:995 its downstream targets 974:995 its downstream targets 974:995 PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. 35723049 4 1 theme CRC 534:536 arg1 data 549:552 publicly available CRC microarray data 515:552 publicly available CRC microarray data 515:552 Analysis of publicly available CRC microarray data determined that PGM3 is upregulated in CRC tumor tissues. 35723049 1 2 from N- 151:152 arg1 cancer 192:197 cancer 192:197 cancer 192:197 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 4 3 theme available 524:532 arg1 data 549:552 publicly available CRC microarray data 515:552 publicly available CRC microarray data 515:552 Analysis of publicly available CRC microarray data determined that PGM3 is upregulated in CRC tumor tissues. 35723049 8 4 from target 1202:1207 arg1 CRC 1212:1214 CRC 1212:1214 CRC 1212:1214 Collectively, our findings indicate that PGM3 exhibits tumor-promoting roles by elevating O-GlcNAcylation level and maintaining β-catenin activity, and might serve as a prognostic biomarker and treatment target in CRC. 35723049 2 5 theme HBP 286:288 arg1 role 298:301 its role 294:301 its role in colorectal cancer (CRC) progression 294:340 However, the regulation mechanisms of HBP and its role in colorectal cancer (CRC) progression remain unexplained. 35723049 2 5 theme HBP 286:288 arg1 mechanisms 272:281 the regulation mechanisms 257:281 the regulation mechanisms of HBP 257:288 However, the regulation mechanisms of HBP and its role in colorectal cancer (CRC) progression remain unexplained. 35723049 2 6 from role 298:301 arg1 progression 330:340 colorectal cancer (CRC) progression 306:340 colorectal cancer (CRC) progression 306:340 However, the regulation mechanisms of HBP and its role in colorectal cancer (CRC) progression remain unexplained. 35723049 4 7 theme data 549:552 arg1 Analysis 503:510 Analysis 503:510 Analysis of publicly available CRC microarray data 503:552 Analysis of publicly available CRC microarray data determined that PGM3 is upregulated in CRC tumor tissues. 35723049 7 8 theme targets 989:995 arg1 activity 936:943 β-catenin activity 926:943 β-catenin activity 926:943 PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. 35723049 7 8 theme targets 989:995 arg1 levels 964:969 the expression levels 949:969 the expression levels of its downstream targets 949:995 PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. 35723049 1 9 gly glycosylation 175:187 arg1 cancer 192:197 cancer 192:197 cancer 192:197 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 4 10 theme microarray 538:547 arg1 data 549:552 publicly available CRC microarray data 515:552 publicly available CRC microarray data 515:552 Analysis of publicly available CRC microarray data determined that PGM3 is upregulated in CRC tumor tissues. 35723049 5 11 theme CRC 705:707 arg1 cell 709:712 CRC cell proliferation and migration 705:740 CRC cell proliferation and migration 705:740 Furthermore, functional experiments emphasized the significant roles of PGM3 in facilitating CRC cell proliferation and migration. 35723049 8 12 theme treatment 1192:1200 arg1 target 1202:1207 treatment target 1192:1207 treatment target 1192:1207 Collectively, our findings indicate that PGM3 exhibits tumor-promoting roles by elevating O-GlcNAcylation level and maintaining β-catenin activity, and might serve as a prognostic biomarker and treatment target in CRC. 35723049 3 13 from function 475:482 arg1 lines 496:500 CRC cell lines 487:500 CRC cell lines 487:500 This study analyzed the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, and identified its function in CRC cell lines. 35723049 1 14 theme O-linked 158:165 arg1 glycosylation 175:187 O-linked protein glycosylation 158:187 O-linked protein glycosylation 158:187 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 0 15 theme colorectal 48:57 arg1 progression 71:81 colorectal cancer cell progression 48:81 colorectal cancer cell progression 48:81 PGM3 regulates beta-catenin activity to promote colorectal cancer cell progression. 35723049 8 16 theme tumor-promoting 1053:1067 arg1 roles 1069:1073 tumor-promoting roles 1053:1073 tumor-promoting roles 1053:1073 Collectively, our findings indicate that PGM3 exhibits tumor-promoting roles by elevating O-GlcNAcylation level and maintaining β-catenin activity, and might serve as a prognostic biomarker and treatment target in CRC. 35723049 3 17 from enzyme 441:446 arg1 HBP 451:453 HBP 451:453 HBP 451:453 This study analyzed the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, and identified its function in CRC cell lines. 35723049 2 18 theme regulation 261:270 arg1 mechanisms 272:281 the regulation mechanisms 257:281 the regulation mechanisms of HBP 257:288 However, the regulation mechanisms of HBP and its role in colorectal cancer (CRC) progression remain unexplained. 35723049 1 19 theme protein 167:173 arg1 glycosylation 175:187 O-linked protein glycosylation 158:187 O-linked protein glycosylation 158:187 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 1 20 link O-linked 158:165 arg1 glycosylation 175:187 O-linked protein glycosylation 158:187 O-linked protein glycosylation 158:187 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 1 21 theme hexosamine 88:97 arg1 HBP 121:123 HBP 121:123 HBP 121:123 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 1 21 theme hexosamine 88:97 arg1 pathway 112:118 The hexosamine biosynthetic pathway 84:118 The hexosamine biosynthetic pathway (HBP) 84:124 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 8 22 theme β-catenin 1126:1134 arg1 activity 1136:1143 β-catenin activity 1126:1143 β-catenin activity 1126:1143 Collectively, our findings indicate that PGM3 exhibits tumor-promoting roles by elevating O-GlcNAcylation level and maintaining β-catenin activity, and might serve as a prognostic biomarker and treatment target in CRC. 35723049 3 23 theme phosphoglucomutase 406:423 arg1 level 397:401 the expression level 382:401 the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, 382:454 This study analyzed the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, and identified its function in CRC cell lines. 35723049 1 24 theme biosynthetic 99:110 arg1 HBP 121:123 HBP 121:123 HBP 121:123 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 1 24 theme biosynthetic 99:110 arg1 pathway 112:118 The hexosamine biosynthetic pathway 84:118 The hexosamine biosynthetic pathway (HBP) 84:124 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 6 25 from activity 785:792 arg1 CRC 810:812 CRC 810:812 CRC 810:812 Mechanistically, we demonstrated that the activity of β-catenin in CRC was maintained by PGM3-mediated O-GlcNAcylation. 35723049 7 26 theme PGM3 863:866 arg1 knockdown 868:876 PGM3 knockdown 863:876 PGM3 knockdown 863:876 PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. 35723049 5 27 theme significant 663:673 arg1 roles 675:679 the significant roles 659:679 the significant roles of PGM3 in facilitating CRC cell proliferation and migration 659:740 Furthermore, functional experiments emphasized the significant roles of PGM3 in facilitating CRC cell proliferation and migration. 35723049 7 28 theme expression 953:962 arg1 levels 964:969 the expression levels 949:969 the expression levels of its downstream targets 949:995 PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. 35723049 0 29 theme beta-catenin 15:26 arg1 activity 28:35 beta-catenin activity 15:35 beta-catenin activity 15:35 PGM3 regulates beta-catenin activity to promote colorectal cancer cell progression. 35723049 8 30 theme O-GlcNAcylation 1088:1102 arg1 level 1104:1108 O-GlcNAcylation level 1088:1108 O-GlcNAcylation level 1088:1108 Collectively, our findings indicate that PGM3 exhibits tumor-promoting roles by elevating O-GlcNAcylation level and maintaining β-catenin activity, and might serve as a prognostic biomarker and treatment target in CRC. 35723049 3 31 theme key 437:439 arg1 enzyme 441:446 a key enzyme 435:446 a key enzyme in HBP 435:453 This study analyzed the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, and identified its function in CRC cell lines. 35723049 3 31 theme key 437:439 arg1 phosphoglucomutase 406:423 phosphoglucomutase 3 406:425 phosphoglucomutase 3 (PGM3) 406:432 This study analyzed the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, and identified its function in CRC cell lines. 35723049 6 32 theme PGM3-mediated 832:844 arg1 O-GlcNAcylation 846:860 PGM3-mediated O-GlcNAcylation 832:860 PGM3-mediated O-GlcNAcylation 832:860 Mechanistically, we demonstrated that the activity of β-catenin in CRC was maintained by PGM3-mediated O-GlcNAcylation. 35723049 4 33 theme tumor 597:601 arg1 tissues 603:609 CRC tumor tissues 593:609 CRC tumor tissues 593:609 Analysis of publicly available CRC microarray data determined that PGM3 is upregulated in CRC tumor tissues. 35723049 7 34 theme O-GlcNAc 895:902 arg1 transferase 904:914 O-GlcNAc transferase 895:914 O-GlcNAc transferase 895:914 PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. 35723049 5 35 theme PGM3 684:687 arg1 roles 675:679 the significant roles 659:679 the significant roles of PGM3 in facilitating CRC cell proliferation and migration 659:740 Furthermore, functional experiments emphasized the significant roles of PGM3 in facilitating CRC cell proliferation and migration. 35723049 4 36 theme CRC 593:595 arg1 tissues 603:609 CRC tumor tissues 593:609 CRC tumor tissues 593:609 Analysis of publicly available CRC microarray data determined that PGM3 is upregulated in CRC tumor tissues. 35723049 0 37 theme cancer 59:64 arg1 progression 71:81 colorectal cancer cell progression 48:81 colorectal cancer cell progression 48:81 PGM3 regulates beta-catenin activity to promote colorectal cancer cell progression. 35723049 5 38 theme functional 625:634 arg1 experiments 636:646 functional experiments 625:646 functional experiments 625:646 Furthermore, functional experiments emphasized the significant roles of PGM3 in facilitating CRC cell proliferation and migration. 35723049 3 39 theme expression 386:395 arg1 level 397:401 the expression level 382:401 the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, 382:454 This study analyzed the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, and identified its function in CRC cell lines. 35723049 5 40 dep cell 709:712 arg1 migration 732:740 migration 732:740 migration 732:740 Furthermore, functional experiments emphasized the significant roles of PGM3 in facilitating CRC cell proliferation and migration. 35723049 5 40 dep cell 709:712 arg1 proliferation 714:726 proliferation 714:726 proliferation 714:726 Furthermore, functional experiments emphasized the significant roles of PGM3 in facilitating CRC cell proliferation and migration. 35723049 2 41 from mechanisms 272:281 arg1 progression 330:340 colorectal cancer (CRC) progression 306:340 colorectal cancer (CRC) progression 306:340 However, the regulation mechanisms of HBP and its role in colorectal cancer (CRC) progression remain unexplained. 35723049 7 42 theme β-catenin 926:934 arg1 activity 936:943 β-catenin activity 926:943 β-catenin activity 926:943 PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. 35723049 2 43 theme cancer 317:322 arg1 progression 330:340 colorectal cancer (CRC) progression 306:340 colorectal cancer (CRC) progression 306:340 However, the regulation mechanisms of HBP and its role in colorectal cancer (CRC) progression remain unexplained. 35723049 7 44 theme transferase 904:914 arg1 knockdown 868:876 PGM3 knockdown 863:876 PGM3 knockdown 863:876 PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. 35723049 7 44 theme transferase 904:914 arg1 inhibition 881:890 inhibition 881:890 inhibition of O-GlcNAc transferase 881:914 PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. 35723049 1 45 theme critical 215:222 arg1 roles 224:228 critical roles 215:228 critical roles 215:228 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 3 46 theme CRC 487:489 arg1 lines 496:500 CRC cell lines 487:500 CRC cell lines 487:500 This study analyzed the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, and identified its function in CRC cell lines. 35723049 8 47 from biomarker 1178:1186 arg1 CRC 1212:1214 CRC 1212:1214 CRC 1212:1214 Collectively, our findings indicate that PGM3 exhibits tumor-promoting roles by elevating O-GlcNAcylation level and maintaining β-catenin activity, and might serve as a prognostic biomarker and treatment target in CRC. 35723049 3 48 theme cell 491:494 arg1 lines 496:500 CRC cell lines 487:500 CRC cell lines 487:500 This study analyzed the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, and identified its function in CRC cell lines. 35723049 1 49 from glycosylation 175:187 arg1 cancer 192:197 cancer 192:197 cancer 192:197 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 2 50 theme colorectal 306:315 arg1 CRC 325:327 CRC 325:327 CRC 325:327 However, the regulation mechanisms of HBP and its role in colorectal cancer (CRC) progression remain unexplained. 35723049 2 50 theme colorectal 306:315 arg1 cancer 317:322 colorectal cancer 306:322 colorectal cancer (CRC) progression 306:340 However, the regulation mechanisms of HBP and its role in colorectal cancer (CRC) progression remain unexplained. 35723049 6 51 theme β-catenin 797:805 arg1 activity 785:792 the activity 781:792 the activity of β-catenin in CRC 781:812 Mechanistically, we demonstrated that the activity of β-catenin in CRC was maintained by PGM3-mediated O-GlcNAcylation. 35723049 0 52 theme cell 66:69 arg1 progression 71:81 colorectal cancer cell progression 48:81 colorectal cancer cell progression 48:81 PGM3 regulates beta-catenin activity to promote colorectal cancer cell progression. 35723049 1 53 theme abnormal 142:149 arg1 N- 151:152 abnormal N- 142:152 abnormal N- 142:152 The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. 35723049 8 54 theme prognostic 1167:1176 arg1 PGM3 1039:1042 PGM3 1039:1042 PGM3 1039:1042 Collectively, our findings indicate that PGM3 exhibits tumor-promoting roles by elevating O-GlcNAcylation level and maintaining β-catenin activity, and might serve as a prognostic biomarker and treatment target in CRC. 35723049 8 54 theme prognostic 1167:1176 arg1 biomarker 1178:1186 a prognostic biomarker 1165:1186 a prognostic biomarker 1165:1186 Collectively, our findings indicate that PGM3 exhibits tumor-promoting roles by elevating O-GlcNAcylation level and maintaining β-catenin activity, and might serve as a prognostic biomarker and treatment target in CRC. 35227760 0 0 theme Zyxin 96:100 arg1 localization 42:53 the nuclear localization 30:53 the nuclear localization of the focal adhesion-associated protein Zyxin 30:100 O-GlcNAc transferase promotes the nuclear localization of the focal adhesion-associated protein Zyxin to regulate UV-induced cell death. 35227760 7 1 theme Zyxin 1114:1118 arg1 O-GlcNAcylation 1095:1109 the O-GlcNAcylation 1091:1109 the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin 1091:1167 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 6 2 theme Ser-169 698:704 arg1 O-GlcNAcylation 679:693 O-GlcNAcylation 679:693 O-GlcNAcylation 679:693 In addition, O-GlcNAcylation of Ser-169, but not Ser-246, enhances its interaction with 14-3-3γ, which is a phosphoserine/threonine-binding protein and is reported to bind with phosphorylated Zyxin. 35227760 0 3 theme protein 88:94 arg1 Zyxin 96:100 the focal adhesion-associated protein Zyxin 58:100 the focal adhesion-associated protein Zyxin 58:100 O-GlcNAc transferase promotes the nuclear localization of the focal adhesion-associated protein Zyxin to regulate UV-induced cell death. 35227760 6 4 theme phosphoserine/threonine-binding 774:804 arg1 protein 806:812 a phosphoserine/threonine-binding protein 772:812 a phosphoserine/threonine-binding protein 772:812 In addition, O-GlcNAcylation of Ser-169, but not Ser-246, enhances its interaction with 14-3-3γ, which is a phosphoserine/threonine-binding protein and is reported to bind with phosphorylated Zyxin. 35227760 6 4 theme phosphoserine/threonine-binding 774:804 arg1 interaction 737:747 its interaction 733:747 its interaction 733:747 In addition, O-GlcNAcylation of Ser-169, but not Ser-246, enhances its interaction with 14-3-3γ, which is a phosphoserine/threonine-binding protein and is reported to bind with phosphorylated Zyxin. 35227760 4 5 theme O-linked 457:464 arg1 transferase 484:494 O-linked GlcNAc [O-GlcNAc] transferase 457:494 O-linked GlcNAc [O-GlcNAc] transferase 457:494 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 4 5 theme O-linked 457:464 arg1 transferase 444:454 the GlcNAc transferase 433:454 the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) 433:495 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 0 6 theme cell 125:128 arg1 death 130:134 UV-induced cell death 114:134 UV-induced cell death 114:134 O-GlcNAc transferase promotes the nuclear localization of the focal adhesion-associated protein Zyxin to regulate UV-induced cell death. 35227760 2 7 theme signal 266:271 arg1 transduction 273:284 signal transduction 266:284 signal transduction between focal adhesions and the nuclear compartment 266:336 Zyxin also plays a role in signal transduction between focal adhesions and the nuclear compartment. 35227760 8 8 theme protein 1234:1240 arg1 kinase 1242:1247 homeodomain-interacting protein kinase 2 1210:1249 homeodomain-interacting protein kinase 2 stability 1210:1259 Finally, Zyxin in the nucleus maintains homeodomain-interacting protein kinase 2 stability and promotes UV-induced cell death. 35227760 0 9 theme UV-induced 114:123 arg1 death 130:134 UV-induced cell death 114:134 UV-induced cell death 114:134 O-GlcNAc transferase promotes the nuclear localization of the focal adhesion-associated protein Zyxin to regulate UV-induced cell death. 35227760 4 10 theme [O-GlcNAc 473:481 arg1 transferase 484:494 O-linked GlcNAc [O-GlcNAc] transferase 457:494 O-linked GlcNAc [O-GlcNAc] transferase 457:494 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 4 10 theme [O-GlcNAc 473:481 arg1 transferase 444:454 the GlcNAc transferase 433:454 the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) 433:495 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 7 11 theme Zyxin 1163:1167 arg1 location 1151:1158 the nuclear location 1139:1158 the nuclear location of Zyxin 1139:1167 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 8 12 theme homeodomain-interacting 1210:1232 arg1 kinase 1242:1247 homeodomain-interacting protein kinase 2 1210:1249 homeodomain-interacting protein kinase 2 stability 1210:1259 Finally, Zyxin in the nucleus maintains homeodomain-interacting protein kinase 2 stability and promotes UV-induced cell death. 35227760 4 13 theme GlcNAc 466:471 arg1 transferase 484:494 O-linked GlcNAc [O-GlcNAc] transferase 457:494 O-linked GlcNAc [O-GlcNAc] transferase 457:494 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 4 13 theme GlcNAc 466:471 arg1 transferase 444:454 the GlcNAc transferase 433:454 the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) 433:495 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 7 14 theme UV 1068:1069 arg1 treatment 1071:1079 UV treatment 1068:1079 UV treatment 1068:1079 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 7 15 theme nuclear 918:924 arg1 localization 926:937 the nuclear localization 914:937 the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation 914:976 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 1 16 theme cell 194:197 arg1 migration 199:207 cell migration 194:207 cell migration 194:207 Zyxin is a zinc-binding phosphoprotein known to regulate cell migration, adhesion, and cell survival. 35227760 0 17 theme O-GlcNAc 0:7 arg1 transferase 9:19 O-GlcNAc transferase 0:19 O-GlcNAc transferase 0:19 O-GlcNAc transferase promotes the nuclear localization of the focal adhesion-associated protein Zyxin to regulate UV-induced cell death. 35227760 4 18 theme nuclear 538:544 arg1 localization 546:557 its nuclear localization 534:557 its nuclear localization 534:557 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 8 19 theme kinase 1242:1247 arg1 stability 1251:1259 homeodomain-interacting protein kinase 2 stability 1210:1259 homeodomain-interacting protein kinase 2 stability 1210:1259 Finally, Zyxin in the nucleus maintains homeodomain-interacting protein kinase 2 stability and promotes UV-induced cell death. 35227760 3 20 theme Zyxin 365:369 arg1 unclear 401:407 unclear 401:407 unclear 401:407 However, the mechanism of Zyxin shuttling to nucleus is still unclear. 35227760 3 20 theme Zyxin 365:369 arg1 mechanism 352:360 the mechanism 348:360 the mechanism of Zyxin shuttling to nucleus 348:390 However, the mechanism of Zyxin shuttling to nucleus is still unclear. 35227760 5 21 theme O-GlcNAc 573:580 arg1 transferase 582:592 O-GlcNAc transferase 573:592 O-GlcNAc transferase 573:592 We show that O-GlcNAc transferase O-GlcNAcylates Zyxin at two residues, serine 169 (Ser-169) and Ser-246. 35227760 7 22 theme Zyxin 942:946 arg1 localization 926:937 the nuclear localization 914:937 the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation 914:976 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 9 23 theme cell 1449:1452 arg1 death 1454:1458 UV-induced cell death 1438:1458 UV-induced cell death 1438:1458 In conclusion, we uncover that the nuclear localization of Zyxin can be regulated by its O-GlcNAcylation, and that this protein may regulate UV-induced cell death. 35227760 9 24 theme nuclear 1332:1338 arg1 localization 1340:1351 the nuclear localization 1328:1351 the nuclear localization of Zyxin 1328:1360 In conclusion, we uncover that the nuclear localization of Zyxin can be regulated by its O-GlcNAcylation, and that this protein may regulate UV-induced cell death. 35227760 6 25 theme phosphorylated 843:856 arg1 Zyxin 858:862 phosphorylated Zyxin 843:862 phosphorylated Zyxin 843:862 In addition, O-GlcNAcylation of Ser-169, but not Ser-246, enhances its interaction with 14-3-3γ, which is a phosphoserine/threonine-binding protein and is reported to bind with phosphorylated Zyxin. 35227760 2 26 theme focal 294:298 arg1 adhesions 300:308 focal adhesions 294:308 focal adhesions 294:308 Zyxin also plays a role in signal transduction between focal adhesions and the nuclear compartment. 35227760 5 27 from residues 622:629 arg1 Zyxin 609:613 Zyxin 609:613 Zyxin at two residues, serine 169 (Ser-169) and Ser-246 609:663 We show that O-GlcNAc transferase O-GlcNAcylates Zyxin at two residues, serine 169 (Ser-169) and Ser-246. 35227760 7 28 theme sequence 1044:1051 arg1 function 995:1002 the function 991:1002 the function of the N-terminal nuclear export signal sequence 991:1051 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 9 29 theme UV-induced 1438:1447 arg1 death 1454:1458 UV-induced cell death 1438:1458 UV-induced cell death 1438:1458 In conclusion, we uncover that the nuclear localization of Zyxin can be regulated by its O-GlcNAcylation, and that this protein may regulate UV-induced cell death. 35227760 8 30 theme UV-induced 1274:1283 arg1 death 1290:1294 UV-induced cell death 1274:1294 UV-induced cell death 1274:1294 Finally, Zyxin in the nucleus maintains homeodomain-interacting protein kinase 2 stability and promotes UV-induced cell death. 35227760 0 31 theme nuclear 34:40 arg1 localization 42:53 the nuclear localization 30:53 the nuclear localization of the focal adhesion-associated protein Zyxin 30:100 O-GlcNAc transferase promotes the nuclear localization of the focal adhesion-associated protein Zyxin to regulate UV-induced cell death. 35227760 6 32 with interaction 737:747 arg1 14-3-3γ 754:760 14-3-3γ 754:760 14-3-3γ 754:760 In addition, O-GlcNAcylation of Ser-169, but not Ser-246, enhances its interaction with 14-3-3γ, which is a phosphoserine/threonine-binding protein and is reported to bind with phosphorylated Zyxin. 35227760 7 33 theme nuclear 1143:1149 arg1 location 1151:1158 the nuclear location 1139:1158 the nuclear location of Zyxin 1139:1167 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 9 34 theme Zyxin 1356:1360 arg1 localization 1340:1351 the nuclear localization 1328:1351 the nuclear localization of Zyxin 1328:1360 In conclusion, we uncover that the nuclear localization of Zyxin can be regulated by its O-GlcNAcylation, and that this protein may regulate UV-induced cell death. 35227760 7 35 theme export 1030:1035 arg1 sequence 1044:1051 the N-terminal nuclear export signal sequence 1007:1051 the N-terminal nuclear export signal sequence 1007:1051 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 4 36 theme GlcNAc 437:442 arg1 transferase 484:494 O-linked GlcNAc [O-GlcNAc] transferase 457:494 O-linked GlcNAc [O-GlcNAc] transferase 457:494 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 4 36 theme GlcNAc 437:442 arg1 transferase 444:454 the GlcNAc transferase 433:454 the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) 433:495 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 4 37 link O-linked 457:464 arg1 transferase 484:494 O-linked GlcNAc [O-GlcNAc] transferase 457:494 O-linked GlcNAc [O-GlcNAc] transferase 457:494 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 4 37 link O-linked 457:464 arg1 transferase 444:454 the GlcNAc transferase 433:454 the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) 433:495 Here, we identify that the GlcNAc transferase (O-linked GlcNAc [O-GlcNAc] transferase) can O-GlcNAcylate Zyxin and regulate its nuclear localization. 35227760 7 38 theme signal 1037:1042 arg1 sequence 1044:1051 the N-terminal nuclear export signal sequence 1007:1051 the N-terminal nuclear export signal sequence 1007:1051 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 8 39 theme cell 1285:1288 arg1 death 1290:1294 UV-induced cell death 1274:1294 UV-induced cell death 1274:1294 Finally, Zyxin in the nucleus maintains homeodomain-interacting protein kinase 2 stability and promotes UV-induced cell death. 35227760 7 40 theme N-terminal 1011:1020 arg1 sequence 1044:1051 the N-terminal nuclear export signal sequence 1007:1051 the N-terminal nuclear export signal sequence 1007:1051 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 1 41 theme cell 224:227 arg1 survival 229:236 cell survival 224:236 cell survival 224:236 Zyxin is a zinc-binding phosphoprotein known to regulate cell migration, adhesion, and cell survival. 35227760 7 42 theme nuclear 1022:1028 arg1 sequence 1044:1051 the N-terminal nuclear export signal sequence 1007:1051 the N-terminal nuclear export signal sequence 1007:1051 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 2 43 theme nuclear 318:324 arg1 compartment 326:336 the nuclear compartment 314:336 the nuclear compartment 314:336 Zyxin also plays a role in signal transduction between focal adhesions and the nuclear compartment. 35227760 0 44 theme adhesion-associated 68:86 arg1 Zyxin 96:100 the focal adhesion-associated protein Zyxin 58:100 the focal adhesion-associated protein Zyxin 58:100 O-GlcNAc transferase promotes the nuclear localization of the focal adhesion-associated protein Zyxin to regulate UV-induced cell death. 35227760 0 45 theme focal 62:66 arg1 Zyxin 96:100 the focal adhesion-associated protein Zyxin 58:100 the focal adhesion-associated protein Zyxin 58:100 O-GlcNAc transferase promotes the nuclear localization of the focal adhesion-associated protein Zyxin to regulate UV-induced cell death. 35227760 8 46 from Zyxin 1179:1183 arg1 nucleus 1192:1198 the nucleus 1188:1198 the nucleus 1188:1198 Finally, Zyxin in the nucleus maintains homeodomain-interacting protein kinase 2 stability and promotes UV-induced cell death. 35227760 7 47 theme Ser-169 954:960 arg1 O-GlcNAcylation 962:976 Ser-169 O-GlcNAcylation 954:976 Ser-169 O-GlcNAcylation 954:976 Furthermore, we found that 14-3-3γ could promote the nuclear localization of Zyxin after Ser-169 O-GlcNAcylation by affecting the function of the N-terminal nuclear export signal sequence; functionally, UV treatment increases the O-GlcNAcylation of Zyxin, which may enhance the nuclear location of Zyxin. 35227760 1 48 theme zinc-binding 148:159 arg1 Zyxin 137:141 Zyxin 137:141 Zyxin 137:141 Zyxin is a zinc-binding phosphoprotein known to regulate cell migration, adhesion, and cell survival. 35227760 1 48 theme zinc-binding 148:159 arg1 phosphoprotein 161:174 a zinc-binding phosphoprotein 146:174 a zinc-binding phosphoprotein known to regulate cell migration, adhesion, and cell survival 146:236 Zyxin is a zinc-binding phosphoprotein known to regulate cell migration, adhesion, and cell survival. 36291660 5 0 theme uveal 825:829 arg1 cells 840:844 uveal melanoma cells 825:844 uveal melanoma cells 825:844 This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. 36291660 7 1 from number 1065:1070 arg1 progression 1103:1113 melanoma progression 1094:1113 melanoma progression of cell proliferation, adhesion, migration, and invasion 1094:1170 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 8 2 from ligand 1211:1216 arg1 melanoma 1229:1236 melanoma 1229:1236 melanoma 1229:1236 Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. 36291660 1 3 theme Melanoma 133:140 arg1 molecule 156:163 Melanoma cell adhesion molecule 133:163 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) 133:184 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 1 3 theme Melanoma 133:140 arg1 protein 226:232 a heavily glycosylated transmembrane protein 189:232 a heavily glycosylated transmembrane protein 189:232 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 9 4 theme melanoma 1420:1427 arg1 treatment 1429:1437 melanoma treatment 1420:1437 melanoma treatment 1420:1437 Targeting the galectin-3-MCAM interaction may potentially be a useful therapeutic strategy for melanoma treatment. 36291660 1 5 theme glycosylated 199:210 arg1 molecule 156:163 Melanoma cell adhesion molecule 133:163 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) 133:184 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 1 5 theme glycosylated 199:210 arg1 protein 226:232 a heavily glycosylated transmembrane protein 189:232 a heavily glycosylated transmembrane protein 189:232 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 7 6 theme cell 1118:1121 arg1 progression 1103:1113 melanoma progression 1094:1113 melanoma progression of cell proliferation, adhesion, migration, and invasion 1094:1170 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 8 7 theme melanoma 1303:1310 arg1 progression 1312:1322 MCAM-mediated melanoma progression 1289:1322 MCAM-mediated melanoma progression 1289:1322 Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. 36291660 1 8 theme transmembrane 212:224 arg1 molecule 156:163 Melanoma cell adhesion molecule 133:163 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) 133:184 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 1 8 theme transmembrane 212:224 arg1 protein 226:232 a heavily glycosylated transmembrane protein 189:232 a heavily glycosylated transmembrane protein 189:232 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 6 9 theme signalling 1020:1029 arg1 surface 968:974 cell surface 963:974 cell surface 963:974 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 6 9 theme signalling 1020:1029 arg1 activation 991:1000 subsequent activation 980:1000 subsequent activation of downstream AKT signalling 980:1029 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 6 10 theme MCAM 927:930 arg1 dimerization 932:943 MCAM dimerization 927:943 MCAM dimerization 927:943 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 5 11 theme galactoside-binding 664:682 arg1 protein 684:690 a galactoside-binding protein 662:690 a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma 662:756 This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. 36291660 5 11 theme galactoside-binding 664:682 arg1 galectin-3 650:659 galectin-3 650:659 galectin-3 650:659 This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. 36291660 5 12 theme cells 840:844 arg1 surface 800:806 the surface 796:806 the surface of both skin and uveal melanoma cells 796:844 This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. 36291660 6 13 theme downstream 1005:1014 arg1 signalling 1020:1029 downstream AKT signalling 1005:1029 downstream AKT signalling 1005:1029 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 1 14 theme cell 142:145 arg1 molecule 156:163 Melanoma cell adhesion molecule 133:163 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) 133:184 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 1 14 theme cell 142:145 arg1 protein 226:232 a heavily glycosylated transmembrane protein 189:232 a heavily glycosylated transmembrane protein 189:232 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 0 15 theme Melanoma 65:72 arg1 Cells 74:78 Melanoma Cells 65:78 Melanoma Cells 65:78 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 0 16 from Ligand 32:37 arg1 Cells 74:78 Melanoma Cells 65:78 Melanoma Cells 65:78 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 1 17 gly glycosylated 199:210 arg1 molecule 156:163 Melanoma cell adhesion molecule 133:163 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) 133:184 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 1 17 gly glycosylated 199:210 arg1 protein 226:232 a heavily glycosylated transmembrane protein 189:232 a heavily glycosylated transmembrane protein 189:232 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 3 18 theme vital 466:470 arg1 role 472:475 a vital role 464:475 a vital role 464:475 More and more evidence has shown that activation of the MCAM on cell surface plays a vital role in melanoma progression and metastasis. 36291660 6 19 theme AKT 1016:1018 arg1 signalling 1020:1029 downstream AKT signalling 1005:1029 downstream AKT signalling 1005:1029 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 1 20 theme adhesion 147:154 arg1 molecule 156:163 Melanoma cell adhesion molecule 133:163 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) 133:184 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 1 20 theme adhesion 147:154 arg1 protein 226:232 a heavily glycosylated transmembrane protein 189:232 a heavily glycosylated transmembrane protein 189:232 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 7 21 from steps 1085:1089 arg1 progression 1103:1113 melanoma progression 1094:1113 melanoma progression of cell proliferation, adhesion, migration, and invasion 1094:1170 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 9 22 theme therapeutic 1395:1405 arg1 strategy 1407:1414 a useful therapeutic strategy 1386:1414 a useful therapeutic strategy for melanoma treatment 1386:1437 Targeting the galectin-3-MCAM interaction may potentially be a useful therapeutic strategy for melanoma treatment. 36291660 7 23 theme melanoma 1094:1101 arg1 progression 1103:1113 melanoma progression 1094:1113 melanoma progression of cell proliferation, adhesion, migration, and invasion 1094:1170 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 4 24 from activation 578:587 arg1 melanoma 592:599 melanoma 592:599 melanoma 592:599 However, the natural MCAM binding ligand that initiates MCAM activation in melanoma so far remains elusive. 36291660 3 25 theme More 381:384 arg1 evidence 395:402 More and more evidence 381:402 More and more evidence 381:402 More and more evidence has shown that activation of the MCAM on cell surface plays a vital role in melanoma progression and metastasis. 36291660 0 26 theme Natural 16:22 arg1 Ligand 32:37 a Natural Binding Ligand 14:37 a Natural Binding Ligand of MCAM 14:45 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 0 26 theme Natural 16:22 arg1 Galectin-3 0:9 Galectin-3 0:9 Galectin-3 0:9 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 8 27 theme natural 1195:1201 arg1 ligand 1211:1216 a natural binding ligand 1193:1216 a natural binding ligand of MCAM in melanoma 1193:1236 Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. 36291660 8 27 theme natural 1195:1201 arg1 galectin-3 1179:1188 galectin-3 1179:1188 galectin-3 1179:1188 Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. 36291660 0 28 dep CD146 48:52 arg1 MUC18 55:59 MUC18 55:59 MUC18 55:59 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 6 29 link O-linked 882:896 arg1 glycans 898:904 O-linked glycans 882:904 O-linked glycans on the MCAM 882:916 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 9 30 theme useful 1388:1393 arg1 strategy 1407:1414 a useful therapeutic strategy 1386:1414 a useful therapeutic strategy for melanoma treatment 1386:1437 Targeting the galectin-3-MCAM interaction may potentially be a useful therapeutic strategy for melanoma treatment. 36291660 7 31 theme steps 1085:1089 arg1 number 1065:1070 a number 1063:1070 a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion 1063:1170 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 6 32 theme O-linked 882:896 arg1 glycans 898:904 O-linked glycans 882:904 O-linked glycans on the MCAM 882:916 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 7 33 from progression 1103:1113 arg1 number 1065:1070 a number 1063:1070 a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion 1063:1170 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 2 34 theme primary 299:305 arg1 melanoma 307:314 advanced primary melanoma 290:314 advanced primary melanoma 290:314 It is expressed in advanced primary melanoma and metastasis but rarely in benign naevi or normal melanocytes. 36291660 2 35 theme normal 361:366 arg1 melanocytes 368:378 normal melanocytes 361:378 normal melanocytes 361:378 It is expressed in advanced primary melanoma and metastasis but rarely in benign naevi or normal melanocytes. 36291660 7 36 theme number 1065:1070 arg1 increases 1050:1058 the increases 1046:1058 the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion 1046:1170 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 6 37 theme cell 963:966 arg1 surface 968:974 cell surface 963:974 cell surface 963:974 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 1 38 dep molecule 156:163 arg1 MUC18 179:183 MUC18 179:183 MUC18 179:183 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 1 38 dep molecule 156:163 arg1 MCAM 166:169 MCAM 166:169 MCAM 166:169 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 6 39 theme subsequent 980:989 arg1 activation 991:1000 subsequent activation 980:1000 subsequent activation of downstream AKT signalling 980:1029 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 1 40 theme CD146 172:176 arg1 MUC18 179:183 MUC18 179:183 MUC18 179:183 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 1 40 theme CD146 172:176 arg1 MCAM 166:169 MCAM 166:169 MCAM 166:169 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 2 41 theme benign 345:350 arg1 naevi 352:356 benign naevi 345:356 benign naevi 345:356 It is expressed in advanced primary melanoma and metastasis but rarely in benign naevi or normal melanocytes. 36291660 1 42 theme melanoma 250:257 arg1 metastasis 259:268 melanoma metastasis 250:268 melanoma metastasis 250:268 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 0 43 theme Binding 24:30 arg1 Ligand 32:37 a Natural Binding Ligand 14:37 a Natural Binding Ligand of MCAM 14:45 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 0 43 theme Binding 24:30 arg1 Galectin-3 0:9 Galectin-3 0:9 Galectin-3 0:9 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 7 44 theme important 1075:1083 arg1 steps 1085:1089 important steps 1075:1089 important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion 1075:1170 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 5 45 from MCAM 788:791 arg1 surface 800:806 the surface 796:806 the surface of both skin and uveal melanoma cells 796:844 This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. 36291660 4 46 theme MCAM 573:576 arg1 activation 578:587 MCAM activation 573:587 MCAM activation in melanoma 573:599 However, the natural MCAM binding ligand that initiates MCAM activation in melanoma so far remains elusive. 36291660 0 47 theme MCAM 42:45 arg1 Ligand 32:37 a Natural Binding Ligand 14:37 a Natural Binding Ligand of MCAM 14:45 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 0 47 theme MCAM 42:45 arg1 Galectin-3 0:9 Galectin-3 0:9 Galectin-3 0:9 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 1 48 theme metastasis 259:268 arg1 marker 240:245 a marker 238:245 a marker of melanoma metastasis 238:268 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 1 48 theme metastasis 259:268 arg1 molecule 156:163 Melanoma cell adhesion molecule 133:163 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) 133:184 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 1 48 theme metastasis 259:268 arg1 protein 226:232 a heavily glycosylated transmembrane protein 189:232 a heavily glycosylated transmembrane protein 189:232 Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. 36291660 0 49 dep Ligand 32:37 arg1 CD146 48:52 CD146 48:52 CD146 48:52 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 2 50 theme advanced 290:297 arg1 melanoma 307:314 advanced primary melanoma 290:314 advanced primary melanoma 290:314 It is expressed in advanced primary melanoma and metastasis but rarely in benign naevi or normal melanocytes. 36291660 6 51 from glycans 898:904 arg1 MCAM 913:916 the MCAM 909:916 the MCAM 909:916 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 0 52 theme Melanoma 111:118 arg1 Progression 120:130 Melanoma Progression 111:130 Melanoma Progression 111:130 Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. 36291660 3 53 theme cell 445:448 arg1 surface 450:456 cell surface 445:456 cell surface 445:456 More and more evidence has shown that activation of the MCAM on cell surface plays a vital role in melanoma progression and metastasis. 36291660 3 54 theme MCAM 437:440 arg1 activation 419:428 activation 419:428 activation of the MCAM on cell surface 419:456 More and more evidence has shown that activation of the MCAM on cell surface plays a vital role in melanoma progression and metastasis. 36291660 6 55 theme galectin-3 858:867 arg1 Binding 847:853 Binding 847:853 Binding 847:853 Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. 36291660 7 56 dep cell 1118:1121 arg1 invasion 1163:1170 invasion 1163:1170 invasion 1163:1170 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 7 56 dep cell 1118:1121 arg1 adhesion 1138:1145 adhesion 1138:1145 adhesion 1138:1145 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 7 56 dep cell 1118:1121 arg1 proliferation 1123:1135 proliferation 1123:1135 proliferation 1123:1135 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 7 56 dep cell 1118:1121 arg1 migration 1148:1156 migration 1148:1156 migration 1148:1156 This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. 36291660 3 57 from activation 419:428 arg1 surface 450:456 cell surface 445:456 cell surface 445:456 More and more evidence has shown that activation of the MCAM on cell surface plays a vital role in melanoma progression and metastasis. 36291660 8 58 theme MCAM-mediated 1289:1301 arg1 progression 1312:1322 MCAM-mediated melanoma progression 1289:1322 MCAM-mediated melanoma progression 1289:1322 Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. 36291660 5 59 theme melanoma 831:838 arg1 cells 840:844 uveal melanoma cells 825:844 uveal melanoma cells 825:844 This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. 36291660 3 60 theme melanoma 480:487 arg1 progression 489:499 melanoma progression 480:499 melanoma progression 480:499 More and more evidence has shown that activation of the MCAM on cell surface plays a vital role in melanoma progression and metastasis. 36291660 4 61 theme MCAM 538:541 arg1 ligand 551:556 the natural MCAM binding ligand 526:556 the natural MCAM binding ligand that initiates MCAM activation in melanoma 526:599 However, the natural MCAM binding ligand that initiates MCAM activation in melanoma so far remains elusive. 36291660 8 62 theme MCAM 1221:1224 arg1 ligand 1211:1216 a natural binding ligand 1193:1216 a natural binding ligand of MCAM in melanoma 1193:1236 Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. 36291660 8 62 theme MCAM 1221:1224 arg1 galectin-3 1179:1188 galectin-3 1179:1188 galectin-3 1179:1188 Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. 36291660 8 63 theme binding 1203:1209 arg1 ligand 1211:1216 a natural binding ligand 1193:1216 a natural binding ligand of MCAM in melanoma 1193:1236 Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. 36291660 8 63 theme binding 1203:1209 arg1 galectin-3 1179:1188 galectin-3 1179:1188 galectin-3 1179:1188 Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. 36291660 4 64 theme natural 530:536 arg1 ligand 551:556 the natural MCAM binding ligand 526:556 the natural MCAM binding ligand that initiates MCAM activation in melanoma 526:599 However, the natural MCAM binding ligand that initiates MCAM activation in melanoma so far remains elusive. 36291660 5 65 theme skin 816:819 arg1 surface 800:806 the surface 796:806 the surface of both skin and uveal melanoma cells 796:844 This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. 36291660 3 66 theme more 390:393 arg1 evidence 395:402 More and more evidence 381:402 More and more evidence 381:402 More and more evidence has shown that activation of the MCAM on cell surface plays a vital role in melanoma progression and metastasis. 36291660 9 67 theme galectin-3-MCAM 1339:1353 arg1 interaction 1355:1365 the galectin-3-MCAM interaction 1335:1365 the galectin-3-MCAM interaction 1335:1365 Targeting the galectin-3-MCAM interaction may potentially be a useful therapeutic strategy for melanoma treatment. 36291660 5 68 theme many 726:729 arg1 cancers 731:737 many cancers 726:737 many cancers including melanoma 726:756 This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. 36291660 5 68 theme many 726:729 arg1 melanoma 749:756 melanoma 749:756 melanoma 749:756 This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. 36291660 4 69 theme binding 543:549 arg1 ligand 551:556 the natural MCAM binding ligand 526:556 the natural MCAM binding ligand that initiates MCAM activation in melanoma 526:599 However, the natural MCAM binding ligand that initiates MCAM activation in melanoma so far remains elusive. 36285381 12 0 theme balance 1526:1532 arg1 responses 1542:1550 balance defense responses 1526:1550 balance defense responses 1526:1550 Taken together, we propose a SlSEC1-SlC3H39 module, which allows plants to balance defense responses and growth processes. 36285381 5 1 theme gene 649:652 arg1 expression 654:663 gene expression 649:663 gene expression 649:663 SlC3H39 binds to AU-rich elements in the 3'-untranslated region (UTR) to induce mRNA degradation and regulates gene expression post-transcriptionally. 36285381 4 2 from tolerance 517:525 arg1 tomato 530:535 tomato 530:535 tomato 530:535 A tandem CCCH zinc-finger protein SlC3H39 negatively modulates cold tolerance in tomato. 36285381 1 3 theme biochemical 149:159 arg1 levels 161:166 the physiological and biochemical levels 127:166 the physiological and biochemical levels 127:166 Plants adapt to cold stress at the physiological and biochemical levels, thus enabling them to maintain growth and development. 36285381 3 4 theme module 354:359 arg1 function 327:334 the function 323:334 the function of SlSEC1-SlC3H39 module in cold tolerance 323:377 We addressed the function of SlSEC1-SlC3H39 module in cold tolerance by using SlSEC1 and SlC3H39 knockout and overexpression tomato lines. 36285381 7 5 link O-linked 812:819 arg1 transferase 841:851 An O-linked N-acetylglucosamine transferase 809:851 An O-linked N-acetylglucosamine transferase SlSEC1 809:858 An O-linked N-acetylglucosamine transferase SlSEC1 physically interacts with SlC3H39 proteins and negatively regulates cold tolerance in tomato. 36285381 11 6 theme SlC3H39 1393:1399 arg1 status 1383:1388 the O-GlcNAclation status 1364:1388 the O-GlcNAclation status of SlC3H39 1364:1399 SlSEC1 promotes the O-GlcNAclation status of SlC3H39 and maintains SlC3H39 function in cold tolerance. 36285381 2 7 theme signals 277:283 arg1 mechanism 247:255 the molecular mechanism 233:255 the molecular mechanism of fine-tuning cold signals 233:283 However, the molecular mechanism of fine-tuning cold signals remains largely unknown. 36285381 9 8 theme cold 1141:1144 arg1 tolerance 1146:1154 cold tolerance 1141:1154 cold tolerance 1141:1154 Genetic analysis shows that SlC3H39 is epistatic to SlSEC1 in cold tolerance. 36285381 6 9 theme genes 802:806 arg1 variety 775:781 a variety 773:781 a variety of cold-responsive genes 773:806 We further validate that SlC3H39 participates in post-transcriptional regulation of a variety of cold-responsive genes. 36285381 6 9 theme genes 802:806 arg1 genes 802:806 cold-responsive genes 786:806 cold-responsive genes 786:806 We further validate that SlC3H39 participates in post-transcriptional regulation of a variety of cold-responsive genes. 36285381 2 10 theme cold 272:275 arg1 signals 277:283 fine-tuning cold signals 260:283 fine-tuning cold signals 260:283 However, the molecular mechanism of fine-tuning cold signals remains largely unknown. 36285381 6 11 theme post-transcriptional 738:757 arg1 regulation 759:768 post-transcriptional regulation 738:768 post-transcriptional regulation of a variety of cold-responsive genes 738:806 We further validate that SlC3H39 participates in post-transcriptional regulation of a variety of cold-responsive genes. 36285381 8 12 theme Further 954:960 arg1 study 962:966 Further study 954:966 Further study 954:966 Further study shows that SlSEC1 is essential for SlC3H39 protein stability and maintains SlC3H39 function in cold tolerance. 36285381 4 13 theme zinc-finger 463:473 arg1 protein 475:481 A tandem CCCH zinc-finger protein SlC3H39 449:489 A tandem CCCH zinc-finger protein SlC3H39 449:489 A tandem CCCH zinc-finger protein SlC3H39 negatively modulates cold tolerance in tomato. 36285381 5 14 theme mRNA 618:621 arg1 degradation 623:633 mRNA degradation 618:633 mRNA degradation 618:633 SlC3H39 binds to AU-rich elements in the 3'-untranslated region (UTR) to induce mRNA degradation and regulates gene expression post-transcriptionally. 36285381 8 15 theme cold 1063:1066 arg1 tolerance 1068:1076 cold tolerance 1063:1076 cold tolerance 1063:1076 Further study shows that SlSEC1 is essential for SlC3H39 protein stability and maintains SlC3H39 function in cold tolerance. 36285381 2 16 theme fine-tuning 260:270 arg1 signals 277:283 fine-tuning cold signals 260:283 fine-tuning cold signals 260:283 However, the molecular mechanism of fine-tuning cold signals remains largely unknown. 36285381 3 17 theme tomato 435:440 arg1 lines 442:446 SlC3H39 knockout and overexpression tomato lines 399:446 SlC3H39 knockout and overexpression tomato lines 399:446 We addressed the function of SlSEC1-SlC3H39 module in cold tolerance by using SlSEC1 and SlC3H39 knockout and overexpression tomato lines. 36285381 3 18 theme SlSEC1-SlC3H39 339:352 arg1 module 354:359 SlSEC1-SlC3H39 module 339:359 SlSEC1-SlC3H39 module 339:359 We addressed the function of SlSEC1-SlC3H39 module in cold tolerance by using SlSEC1 and SlC3H39 knockout and overexpression tomato lines. 36285381 9 19 from SlSEC1 1131:1136 arg1 tolerance 1146:1154 cold tolerance 1141:1154 cold tolerance 1141:1154 Genetic analysis shows that SlC3H39 is epistatic to SlSEC1 in cold tolerance. 36285381 12 20 theme growth 1556:1561 arg1 processes 1563:1571 growth processes 1556:1571 growth processes 1556:1571 Taken together, we propose a SlSEC1-SlC3H39 module, which allows plants to balance defense responses and growth processes. 36285381 5 21 theme 3'-untranslated 579:593 arg1 region 595:600 the 3'-untranslated region 575:600 the 3'-untranslated region (UTR) to induce mRNA degradation 575:633 SlC3H39 binds to AU-rich elements in the 3'-untranslated region (UTR) to induce mRNA degradation and regulates gene expression post-transcriptionally. 36285381 5 21 theme 3'-untranslated 579:593 arg1 UTR 603:605 UTR 603:605 UTR 603:605 SlC3H39 binds to AU-rich elements in the 3'-untranslated region (UTR) to induce mRNA degradation and regulates gene expression post-transcriptionally. 36285381 7 22 theme cold 928:931 arg1 tolerance 933:941 cold tolerance 928:941 cold tolerance in tomato 928:951 An O-linked N-acetylglucosamine transferase SlSEC1 physically interacts with SlC3H39 proteins and negatively regulates cold tolerance in tomato. 36285381 11 23 from function 1423:1430 arg1 tolerance 1440:1448 cold tolerance 1435:1448 cold tolerance 1435:1448 SlSEC1 promotes the O-GlcNAclation status of SlC3H39 and maintains SlC3H39 function in cold tolerance. 36285381 11 24 theme cold 1435:1438 arg1 tolerance 1440:1448 cold tolerance 1435:1448 cold tolerance 1435:1448 SlSEC1 promotes the O-GlcNAclation status of SlC3H39 and maintains SlC3H39 function in cold tolerance. 36285381 11 25 theme SlC3H39 1415:1421 arg1 function 1423:1430 SlC3H39 function 1415:1430 SlC3H39 function in cold tolerance 1415:1448 SlSEC1 promotes the O-GlcNAclation status of SlC3H39 and maintains SlC3H39 function in cold tolerance. 36285381 3 26 theme cold 364:367 arg1 tolerance 369:377 cold tolerance 364:377 cold tolerance 364:377 We addressed the function of SlSEC1-SlC3H39 module in cold tolerance by using SlSEC1 and SlC3H39 knockout and overexpression tomato lines. 36285381 10 27 theme cold 1219:1222 arg1 tolerance 1224:1232 plant cold tolerance 1213:1232 plant cold tolerance 1213:1232 The findings indicate that SlC3H39 negatively modulates plant cold tolerance through post-transcriptional regulation by binding to cold-responding mRNA 3'-UTR and reducing those transcripts. 36285381 5 28 from elements 563:570 arg1 region 595:600 the 3'-untranslated region 575:600 the 3'-untranslated region (UTR) to induce mRNA degradation 575:633 SlC3H39 binds to AU-rich elements in the 3'-untranslated region (UTR) to induce mRNA degradation and regulates gene expression post-transcriptionally. 36285381 5 28 from elements 563:570 arg1 UTR 603:605 UTR 603:605 UTR 603:605 SlC3H39 binds to AU-rich elements in the 3'-untranslated region (UTR) to induce mRNA degradation and regulates gene expression post-transcriptionally. 36285381 10 29 theme plant 1213:1217 arg1 tolerance 1224:1232 plant cold tolerance 1213:1232 plant cold tolerance 1213:1232 The findings indicate that SlC3H39 negatively modulates plant cold tolerance through post-transcriptional regulation by binding to cold-responding mRNA 3'-UTR and reducing those transcripts. 36285381 8 30 theme protein 1011:1017 arg1 stability 1019:1027 SlC3H39 protein stability 1003:1027 SlC3H39 protein stability 1003:1027 Further study shows that SlSEC1 is essential for SlC3H39 protein stability and maintains SlC3H39 function in cold tolerance. 36285381 7 31 theme SlC3H39 886:892 arg1 proteins 894:901 SlC3H39 proteins 886:901 SlC3H39 proteins 886:901 An O-linked N-acetylglucosamine transferase SlSEC1 physically interacts with SlC3H39 proteins and negatively regulates cold tolerance in tomato. 36285381 12 32 theme defense 1534:1540 arg1 responses 1542:1550 balance defense responses 1526:1550 balance defense responses 1526:1550 Taken together, we propose a SlSEC1-SlC3H39 module, which allows plants to balance defense responses and growth processes. 36285381 3 33 theme knockout 407:414 arg1 lines 442:446 SlC3H39 knockout and overexpression tomato lines 399:446 SlC3H39 knockout and overexpression tomato lines 399:446 We addressed the function of SlSEC1-SlC3H39 module in cold tolerance by using SlSEC1 and SlC3H39 knockout and overexpression tomato lines. 36285381 7 34 theme N-acetylglucosamine 821:839 arg1 transferase 841:851 An O-linked N-acetylglucosamine transferase 809:851 An O-linked N-acetylglucosamine transferase SlSEC1 809:858 An O-linked N-acetylglucosamine transferase SlSEC1 physically interacts with SlC3H39 proteins and negatively regulates cold tolerance in tomato. 36285381 9 35 theme Genetic 1079:1085 arg1 analysis 1087:1094 Genetic analysis 1079:1094 Genetic analysis 1079:1094 Genetic analysis shows that SlC3H39 is epistatic to SlSEC1 in cold tolerance. 36285381 4 36 theme CCCH 458:461 arg1 protein 475:481 A tandem CCCH zinc-finger protein SlC3H39 449:489 A tandem CCCH zinc-finger protein SlC3H39 449:489 A tandem CCCH zinc-finger protein SlC3H39 negatively modulates cold tolerance in tomato. 36285381 0 37 theme cold 29:32 arg1 tolerance 34:42 cold tolerance 29:42 cold tolerance 29:42 SEC1-C3H39 module fine-tunes cold tolerance by mediating its target mRNA degradation in tomato. 36285381 7 38 theme transferase 841:851 arg1 SlSEC1 853:858 An O-linked N-acetylglucosamine transferase SlSEC1 809:858 An O-linked N-acetylglucosamine transferase SlSEC1 809:858 An O-linked N-acetylglucosamine transferase SlSEC1 physically interacts with SlC3H39 proteins and negatively regulates cold tolerance in tomato. 36285381 4 39 theme tandem 451:456 arg1 protein 475:481 A tandem CCCH zinc-finger protein SlC3H39 449:489 A tandem CCCH zinc-finger protein SlC3H39 449:489 A tandem CCCH zinc-finger protein SlC3H39 negatively modulates cold tolerance in tomato. 36285381 12 40 theme SlSEC1-SlC3H39 1480:1493 arg1 module 1495:1500 a SlSEC1-SlC3H39 module 1478:1500 a SlSEC1-SlC3H39 module 1478:1500 Taken together, we propose a SlSEC1-SlC3H39 module, which allows plants to balance defense responses and growth processes. 36285381 5 41 theme AU-rich 555:561 arg1 elements 563:570 AU-rich elements 555:570 AU-rich elements in the 3'-untranslated region (UTR) to induce mRNA degradation 555:633 SlC3H39 binds to AU-rich elements in the 3'-untranslated region (UTR) to induce mRNA degradation and regulates gene expression post-transcriptionally. 36285381 10 42 theme post-transcriptional 1242:1261 arg1 regulation 1263:1272 post-transcriptional regulation 1242:1272 post-transcriptional regulation 1242:1272 The findings indicate that SlC3H39 negatively modulates plant cold tolerance through post-transcriptional regulation by binding to cold-responding mRNA 3'-UTR and reducing those transcripts. 36285381 6 43 theme cold-responsive 786:800 arg1 genes 802:806 cold-responsive genes 786:806 cold-responsive genes 786:806 We further validate that SlC3H39 participates in post-transcriptional regulation of a variety of cold-responsive genes. 36285381 1 44 theme cold 112:115 arg1 stress 117:122 cold stress 112:122 cold stress 112:122 Plants adapt to cold stress at the physiological and biochemical levels, thus enabling them to maintain growth and development. 36285381 7 45 theme O-linked 812:819 arg1 transferase 841:851 An O-linked N-acetylglucosamine transferase 809:851 An O-linked N-acetylglucosamine transferase SlSEC1 809:858 An O-linked N-acetylglucosamine transferase SlSEC1 physically interacts with SlC3H39 proteins and negatively regulates cold tolerance in tomato. 36285381 8 46 theme SlC3H39 1003:1009 arg1 stability 1019:1027 SlC3H39 protein stability 1003:1027 SlC3H39 protein stability 1003:1027 Further study shows that SlSEC1 is essential for SlC3H39 protein stability and maintains SlC3H39 function in cold tolerance. 36285381 10 47 theme mRNA 1304:1307 arg1 3'-UTR 1309:1314 cold-responding mRNA 3'-UTR 1288:1314 cold-responding mRNA 3'-UTR 1288:1314 The findings indicate that SlC3H39 negatively modulates plant cold tolerance through post-transcriptional regulation by binding to cold-responding mRNA 3'-UTR and reducing those transcripts. 36285381 11 48 theme O-GlcNAclation 1368:1381 arg1 status 1383:1388 the O-GlcNAclation status 1364:1388 the O-GlcNAclation status of SlC3H39 1364:1399 SlSEC1 promotes the O-GlcNAclation status of SlC3H39 and maintains SlC3H39 function in cold tolerance. 36285381 2 49 theme molecular 237:245 arg1 mechanism 247:255 the molecular mechanism 233:255 the molecular mechanism of fine-tuning cold signals 233:283 However, the molecular mechanism of fine-tuning cold signals remains largely unknown. 36285381 6 50 theme variety 775:781 arg1 regulation 759:768 post-transcriptional regulation 738:768 post-transcriptional regulation of a variety of cold-responsive genes 738:806 We further validate that SlC3H39 participates in post-transcriptional regulation of a variety of cold-responsive genes. 36285381 8 51 from function 1051:1058 arg1 tolerance 1068:1076 cold tolerance 1063:1076 cold tolerance 1063:1076 Further study shows that SlSEC1 is essential for SlC3H39 protein stability and maintains SlC3H39 function in cold tolerance. 36285381 10 52 theme cold-responding 1288:1302 arg1 3'-UTR 1309:1314 cold-responding mRNA 3'-UTR 1288:1314 cold-responding mRNA 3'-UTR 1288:1314 The findings indicate that SlC3H39 negatively modulates plant cold tolerance through post-transcriptional regulation by binding to cold-responding mRNA 3'-UTR and reducing those transcripts. 36285381 0 53 theme mRNA 68:71 arg1 degradation 73:83 its target mRNA degradation 57:83 its target mRNA degradation 57:83 SEC1-C3H39 module fine-tunes cold tolerance by mediating its target mRNA degradation in tomato. 36285381 3 54 from function 327:334 arg1 tolerance 369:377 cold tolerance 364:377 cold tolerance 364:377 We addressed the function of SlSEC1-SlC3H39 module in cold tolerance by using SlSEC1 and SlC3H39 knockout and overexpression tomato lines. 36285381 7 55 from tolerance 933:941 arg1 tomato 946:951 tomato 946:951 tomato 946:951 An O-linked N-acetylglucosamine transferase SlSEC1 physically interacts with SlC3H39 proteins and negatively regulates cold tolerance in tomato. 36285381 0 56 theme target 61:66 arg1 degradation 73:83 its target mRNA degradation 57:83 its target mRNA degradation 57:83 SEC1-C3H39 module fine-tunes cold tolerance by mediating its target mRNA degradation in tomato. 36285381 4 57 theme cold 512:515 arg1 tolerance 517:525 cold tolerance 512:525 cold tolerance in tomato 512:535 A tandem CCCH zinc-finger protein SlC3H39 negatively modulates cold tolerance in tomato. 36285381 8 58 theme SlC3H39 1043:1049 arg1 function 1051:1058 SlC3H39 function 1043:1058 SlC3H39 function in cold tolerance 1043:1076 Further study shows that SlSEC1 is essential for SlC3H39 protein stability and maintains SlC3H39 function in cold tolerance. 36285381 1 59 theme physiological 131:143 arg1 levels 161:166 the physiological and biochemical levels 127:166 the physiological and biochemical levels 127:166 Plants adapt to cold stress at the physiological and biochemical levels, thus enabling them to maintain growth and development. 35285892 5 0 theme genetic 758:764 arg1 manipulations 786:798 genetic and pharmacological manipulations 758:798 genetic and pharmacological manipulations of the O-GlcNAc pathway 758:822 CPS1 O-GlcNAcylation is reversed by calorie restriction and is sensitive to genetic and pharmacological manipulations of the O-GlcNAc pathway. 35285892 7 1 theme prolonged 1013:1021 arg1 fasting 1023:1029 a prolonged fasting 1011:1029 a prolonged fasting 1011:1029 Liver-specific deletion of OGT potentiates CPS1 activity and renders CPS1 irresponsive to further stimulation by a prolonged fasting. 35285892 3 2 theme global 505:510 arg1 levels 521:526 global O-GlcNAc levels 505:526 global O-GlcNAc levels 505:526 Here, we show that global O-GlcNAc levels are increased in multiple tissues of aged mice. 35285892 4 3 theme aged 579:582 arg1 liver 584:588 aged liver 579:588 aged liver 579:588 In aged liver, carbamoyl phosphate synthetase 1 (CPS1) is among the most heavily O-GlcNAcylated proteins. 35285892 8 4 theme longevity 1251:1259 arg1 regulation 1237:1246 nutritional regulation 1225:1246 nutritional regulation of longevity 1225:1259 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 6 5 theme High 825:828 arg1 glucose 830:836 High glucose 825:836 High glucose 825:836 High glucose stimulates CPS1 O-GlcNAcylation and inhibits CPS1 activity. 35285892 1 6 theme intracellular 164:176 arg1 proteins 178:185 intracellular proteins 164:185 intracellular proteins 164:185 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 4 7 from proteins 672:679 arg1 liver 584:588 aged liver 579:588 aged liver 579:588 In aged liver, carbamoyl phosphate synthetase 1 (CPS1) is among the most heavily O-GlcNAcylated proteins. 35285892 5 8 theme calorie 718:724 arg1 restriction 726:736 calorie restriction 718:736 calorie restriction 718:736 CPS1 O-GlcNAcylation is reversed by calorie restriction and is sensitive to genetic and pharmacological manipulations of the O-GlcNAc pathway. 35285892 0 9 from Regulation 0:9 arg1 response 56:63 response 56:63 response to dietary restriction and aging 56:96 Regulation of the urea cycle by CPS1 O-GlcNAcylation in response to dietary restriction and aging. 35285892 8 10 theme key 1079:1081 arg1 O-GlcNAcylation 1058:1072 CPS1 O-GlcNAcylation 1053:1072 CPS1 O-GlcNAcylation 1053:1072 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 8 10 theme key 1079:1081 arg1 step 1111:1114 a key nutrient-sensing regulatory step 1077:1114 a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction 1077:1169 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 3 11 theme multiple 545:552 arg1 tissues 554:560 multiple tissues 545:560 multiple tissues of aged mice 545:573 Here, we show that global O-GlcNAc levels are increased in multiple tissues of aged mice. 35285892 3 12 theme aged 565:568 arg1 mice 570:573 aged mice 565:573 aged mice 565:573 Here, we show that global O-GlcNAc levels are increased in multiple tissues of aged mice. 35285892 3 13 theme mice 570:573 arg1 tissues 554:560 multiple tissues 545:560 multiple tissues of aged mice 545:573 Here, we show that global O-GlcNAc levels are increased in multiple tissues of aged mice. 35285892 8 14 theme regulatory 1100:1109 arg1 O-GlcNAcylation 1058:1072 CPS1 O-GlcNAcylation 1053:1072 CPS1 O-GlcNAcylation 1053:1072 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 8 14 theme regulatory 1100:1109 arg1 step 1111:1114 a key nutrient-sensing regulatory step 1077:1114 a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction 1077:1169 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 7 15 theme further 988:994 arg1 stimulation 996:1006 further stimulation 988:1006 further stimulation by a prolonged fasting 988:1029 Liver-specific deletion of OGT potentiates CPS1 activity and renders CPS1 irresponsive to further stimulation by a prolonged fasting. 35285892 4 16 theme heavily 649:655 arg1 proteins 672:679 the most heavily O-GlcNAcylated proteins 640:679 the most heavily O-GlcNAcylated proteins 640:679 In aged liver, carbamoyl phosphate synthetase 1 (CPS1) is among the most heavily O-GlcNAcylated proteins. 35285892 1 17 theme proteins 178:185 arg1 glycosylation 129:141 O-linked N-acetyl-glucosamine glycosylation 99:141 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins 99:185 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 17 theme proteins 178:185 arg1 process 200:206 a dynamic process 190:206 a dynamic process broadly implicated in age-related disease 190:248 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 17 theme proteins 178:185 arg1 O-GlcNAcylation 144:158 O-GlcNAcylation 144:158 O-GlcNAcylation 144:158 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 8 18 theme nutrient-sensing 1083:1098 arg1 O-GlcNAcylation 1058:1072 CPS1 O-GlcNAcylation 1053:1072 CPS1 O-GlcNAcylation 1053:1072 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 8 18 theme nutrient-sensing 1083:1098 arg1 step 1111:1114 a key nutrient-sensing regulatory step 1077:1114 a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction 1077:1169 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 7 19 theme CPS1 967:970 arg1 irresponsive 972:983 CPS1 irresponsive 967:983 CPS1 irresponsive to further stimulation by a prolonged fasting 967:1029 Liver-specific deletion of OGT potentiates CPS1 activity and renders CPS1 irresponsive to further stimulation by a prolonged fasting. 35285892 5 20 theme pathway 816:822 arg1 manipulations 786:798 genetic and pharmacological manipulations 758:798 genetic and pharmacological manipulations of the O-GlcNAc pathway 758:822 CPS1 O-GlcNAcylation is reversed by calorie restriction and is sensitive to genetic and pharmacological manipulations of the O-GlcNAc pathway. 35285892 2 21 theme enzyme 400:405 arg1 OGA 420:422 OGA 420:422 OGA 420:422 O-GlcNAc transferase (OGT) and the opposing enzyme O-GlcNAcase (OGA) control this nutrient-sensing protein modification in cells. 35285892 2 21 theme enzyme 400:405 arg1 O-GlcNAcase 407:417 the opposing enzyme O-GlcNAcase 387:417 the opposing enzyme O-GlcNAcase (OGA) 387:423 O-GlcNAc transferase (OGT) and the opposing enzyme O-GlcNAcase (OGA) control this nutrient-sensing protein modification in cells. 35285892 5 22 theme O-GlcNAc 807:814 arg1 pathway 816:822 the O-GlcNAc pathway 803:822 the O-GlcNAc pathway 803:822 CPS1 O-GlcNAcylation is reversed by calorie restriction and is sensitive to genetic and pharmacological manipulations of the O-GlcNAc pathway. 35285892 0 23 dep dietary 68:74 arg1 restriction 76:86 restriction 76:86 restriction 76:86 Regulation of the urea cycle by CPS1 O-GlcNAcylation in response to dietary restriction and aging. 35285892 2 24 theme opposing 391:398 arg1 OGA 420:422 OGA 420:422 OGA 420:422 O-GlcNAc transferase (OGT) and the opposing enzyme O-GlcNAcase (OGA) control this nutrient-sensing protein modification in cells. 35285892 2 24 theme opposing 391:398 arg1 O-GlcNAcase 407:417 the opposing enzyme O-GlcNAcase 387:417 the opposing enzyme O-GlcNAcase (OGA) 387:423 O-GlcNAc transferase (OGT) and the opposing enzyme O-GlcNAcase (OGA) control this nutrient-sensing protein modification in cells. 35285892 2 25 theme protein 455:461 arg1 modification 463:474 this nutrient-sensing protein modification 433:474 this nutrient-sensing protein modification 433:474 O-GlcNAc transferase (OGT) and the opposing enzyme O-GlcNAcase (OGA) control this nutrient-sensing protein modification in cells. 35285892 8 26 theme CPS1 1053:1056 arg1 O-GlcNAcylation 1058:1072 CPS1 O-GlcNAcylation 1053:1072 CPS1 O-GlcNAcylation 1053:1072 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 8 26 theme CPS1 1053:1056 arg1 step 1111:1114 a key nutrient-sensing regulatory step 1077:1114 a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction 1077:1169 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 1 27 theme dynamic 192:198 arg1 glycosylation 129:141 O-linked N-acetyl-glucosamine glycosylation 99:141 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins 99:185 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 27 theme dynamic 192:198 arg1 process 200:206 a dynamic process 190:206 a dynamic process broadly implicated in age-related disease 190:248 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 2 28 theme nutrient-sensing 438:453 arg1 modification 463:474 this nutrient-sensing protein modification 433:474 this nutrient-sensing protein modification 433:474 O-GlcNAc transferase (OGT) and the opposing enzyme O-GlcNAcase (OGA) control this nutrient-sensing protein modification in cells. 35285892 8 29 theme urea 1123:1126 arg1 cycle 1128:1132 the urea cycle 1119:1132 the urea cycle 1119:1132 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 8 30 from role 1183:1186 arg1 regulation 1237:1246 nutritional regulation 1225:1246 nutritional regulation of longevity 1225:1259 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 3 31 theme O-GlcNAc 512:519 arg1 levels 521:526 global O-GlcNAc levels 505:526 global O-GlcNAc levels 505:526 Here, we show that global O-GlcNAc levels are increased in multiple tissues of aged mice. 35285892 5 32 theme pharmacological 770:784 arg1 manipulations 786:798 genetic and pharmacological manipulations 758:798 genetic and pharmacological manipulations of the O-GlcNAc pathway 758:822 CPS1 O-GlcNAcylation is reversed by calorie restriction and is sensitive to genetic and pharmacological manipulations of the O-GlcNAc pathway. 35285892 2 33 theme O-GlcNAc 356:363 arg1 OGT 378:380 OGT 378:380 OGT 378:380 O-GlcNAc transferase (OGT) and the opposing enzyme O-GlcNAcase (OGA) control this nutrient-sensing protein modification in cells. 35285892 2 33 theme O-GlcNAc 356:363 arg1 transferase 365:375 O-GlcNAc transferase 356:375 O-GlcNAc transferase (OGT) 356:381 O-GlcNAc transferase (OGT) and the opposing enzyme O-GlcNAcase (OGA) control this nutrient-sensing protein modification in cells. 35285892 6 34 theme CPS1 883:886 arg1 activity 888:895 CPS1 activity 883:895 CPS1 activity 883:895 High glucose stimulates CPS1 O-GlcNAcylation and inhibits CPS1 activity. 35285892 0 35 theme cycle 23:27 arg1 Regulation 0:9 Regulation 0:9 Regulation of the urea cycle by CPS1 O-GlcNAcylation in response to dietary restriction and aging. 0:97 Regulation of the urea cycle by CPS1 O-GlcNAcylation in response to dietary restriction and aging. 35285892 1 36 gly glycosylation 129:141 arg1 proteins 178:185 intracellular proteins 164:185 intracellular proteins 164:185 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 0 37 theme urea 18:21 arg1 cycle 23:27 the urea cycle 14:27 the urea cycle 14:27 Regulation of the urea cycle by CPS1 O-GlcNAcylation in response to dietary restriction and aging. 35285892 8 38 theme mitochondrial 1192:1204 arg1 O-GlcNAcylation 1206:1220 mitochondrial O-GlcNAcylation 1192:1220 mitochondrial O-GlcNAcylation 1192:1220 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 1 39 theme O-linked 99:106 arg1 glycosylation 129:141 O-linked N-acetyl-glucosamine glycosylation 99:141 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins 99:185 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 39 theme O-linked 99:106 arg1 process 200:206 a dynamic process 190:206 a dynamic process broadly implicated in age-related disease 190:248 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 39 theme O-linked 99:106 arg1 O-GlcNAcylation 144:158 O-GlcNAcylation 144:158 O-GlcNAcylation 144:158 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 0 40 theme CPS1 32:35 arg1 O-GlcNAcylation 37:51 CPS1 O-GlcNAcylation 32:51 CPS1 O-GlcNAcylation 32:51 Regulation of the urea cycle by CPS1 O-GlcNAcylation in response to dietary restriction and aging. 35285892 1 41 theme natural 333:339 arg1 process 347:353 the natural aging process 329:353 the natural aging process 329:353 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 6 42 theme CPS1 849:852 arg1 O-GlcNAcylation 854:868 CPS1 O-GlcNAcylation 849:868 CPS1 O-GlcNAcylation 849:868 High glucose stimulates CPS1 O-GlcNAcylation and inhibits CPS1 activity. 35285892 7 43 theme Liver-specific 898:911 arg1 deletion 913:920 Liver-specific deletion 898:920 Liver-specific deletion of OGT 898:927 Liver-specific deletion of OGT potentiates CPS1 activity and renders CPS1 irresponsive to further stimulation by a prolonged fasting. 35285892 1 44 theme N-acetyl-glucosamine 108:127 arg1 glycosylation 129:141 O-linked N-acetyl-glucosamine glycosylation 99:141 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins 99:185 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 44 theme N-acetyl-glucosamine 108:127 arg1 process 200:206 a dynamic process 190:206 a dynamic process broadly implicated in age-related disease 190:248 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 44 theme N-acetyl-glucosamine 108:127 arg1 O-GlcNAcylation 144:158 O-GlcNAcylation 144:158 O-GlcNAcylation 144:158 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 7 45 theme CPS1 941:944 arg1 activity 946:953 CPS1 activity 941:953 CPS1 activity 941:953 Liver-specific deletion of OGT potentiates CPS1 activity and renders CPS1 irresponsive to further stimulation by a prolonged fasting. 35285892 1 46 theme aging 341:345 arg1 process 347:353 the natural aging process 329:353 the natural aging process 329:353 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 47 link O-linked 99:106 arg1 glycosylation 129:141 O-linked N-acetyl-glucosamine glycosylation 99:141 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins 99:185 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 47 link O-linked 99:106 arg1 process 200:206 a dynamic process 190:206 a dynamic process broadly implicated in age-related disease 190:248 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 47 link O-linked 99:106 arg1 O-GlcNAcylation 144:158 O-GlcNAcylation 144:158 O-GlcNAcylation 144:158 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 1 48 dep whether 282:288 arg1 contributes 314:324 contributes 314:324 contributes to the natural aging process 314:353 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 8 49 theme dietary 1151:1157 arg1 restriction 1159:1169 dietary restriction 1151:1169 dietary restriction 1151:1169 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 1 50 theme age-related 230:240 arg1 disease 242:248 age-related disease 230:248 age-related disease 230:248 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 5 51 theme CPS1 682:685 arg1 O-GlcNAcylation 687:701 CPS1 O-GlcNAcylation 682:701 CPS1 O-GlcNAcylation 682:701 CPS1 O-GlcNAcylation is reversed by calorie restriction and is sensitive to genetic and pharmacological manipulations of the O-GlcNAc pathway. 35285892 8 52 theme nutritional 1225:1235 arg1 regulation 1237:1246 nutritional regulation 1225:1246 nutritional regulation of longevity 1225:1259 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 35285892 4 53 theme O-GlcNAcylated 657:670 arg1 proteins 672:679 the most heavily O-GlcNAcylated proteins 640:679 the most heavily O-GlcNAcylated proteins 640:679 In aged liver, carbamoyl phosphate synthetase 1 (CPS1) is among the most heavily O-GlcNAcylated proteins. 35285892 7 54 theme OGT 925:927 arg1 deletion 913:920 Liver-specific deletion 898:920 Liver-specific deletion of OGT 898:927 Liver-specific deletion of OGT potentiates CPS1 activity and renders CPS1 irresponsive to further stimulation by a prolonged fasting. 35285892 4 55 theme carbamoyl 591:599 arg1 synthetase 611:620 carbamoyl phosphate synthetase 1 591:622 carbamoyl phosphate synthetase 1 (CPS1) 591:629 In aged liver, carbamoyl phosphate synthetase 1 (CPS1) is among the most heavily O-GlcNAcylated proteins. 35285892 4 55 theme carbamoyl 591:599 arg1 CPS1 625:628 CPS1 625:628 CPS1 625:628 In aged liver, carbamoyl phosphate synthetase 1 (CPS1) is among the most heavily O-GlcNAcylated proteins. 35285892 1 56 dep remains 258:264 arg1 whether 282:288 whether 282:288 whether 282:288 O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. 35285892 4 57 theme phosphate 601:609 arg1 synthetase 611:620 carbamoyl phosphate synthetase 1 591:622 carbamoyl phosphate synthetase 1 (CPS1) 591:629 In aged liver, carbamoyl phosphate synthetase 1 (CPS1) is among the most heavily O-GlcNAcylated proteins. 35285892 4 57 theme phosphate 601:609 arg1 CPS1 625:628 CPS1 625:628 CPS1 625:628 In aged liver, carbamoyl phosphate synthetase 1 (CPS1) is among the most heavily O-GlcNAcylated proteins. 35285892 8 58 from step 1111:1114 arg1 cycle 1128:1132 the urea cycle 1119:1132 the urea cycle 1119:1132 Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. 36387851 13 0 theme β-cell 1711:1716 arg1 function 1718:1725 β-cell function 1711:1725 β-cell function 1711:1725 Taken together, these data demonstrate that the loss of OGA in β-cells reduces β-cell function, thereby perturbing glucose homeostasis. 36387851 7 1 theme female 955:960 arg1 mice 969:972 young male and female βOGAKO mice 940:972 young male and female βOGAKO mice 940:972 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 3 2 theme severe 496:501 arg1 diabetes 503:510 severe diabetes 496:510 severe diabetes in mice 496:518 Previous work showed that OGT is highly expressed in the pancreas, and we demonstrated that hypo-O-GlcNAcylation in β-cells cause severe diabetes in mice. 36387851 5 3 from failure 716:722 arg1 protection 693:702 protection 693:702 protection from β-cell failure 693:722 In the current study, we hypothesized that hyper-O-GlcNAcylation may confer protection from β-cell failure in high-fat diet (HFD)-induced obesity. 36387851 9 4 theme Total 1170:1174 arg1 content 1184:1190 Total insulin content 1170:1190 Total insulin content 1170:1190 Total insulin content was reduced despite an increase in pro-insulin to insulin ratio in βOGAKO islets. 36387851 7 5 theme young 940:944 arg1 mice 969:972 young male and female βOGAKO mice 940:972 young male and female βOGAKO mice 940:972 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 11 6 theme insulin 1464:1470 arg1 tolerance 1472:1480 insulin tolerance 1464:1480 insulin tolerance 1464:1480 When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. 36387851 4 7 theme nutrient-sensitive 562:579 arg1 OGT 581:583 nutrient-sensitive OGT 562:583 nutrient-sensitive OGT 562:583 These studies show a direct link between nutrient-sensitive OGT and β-cell health and function. 36387851 5 8 theme high-fat 727:734 arg1 HFD 742:744 HFD 742:744 HFD 742:744 In the current study, we hypothesized that hyper-O-GlcNAcylation may confer protection from β-cell failure in high-fat diet (HFD)-induced obesity. 36387851 5 8 theme high-fat 727:734 arg1 diet 736:739 high-fat diet 727:739 high-fat diet (HFD) 727:745 In the current study, we hypothesized that hyper-O-GlcNAcylation may confer protection from β-cell failure in high-fat diet (HFD)-induced obesity. 36387851 7 9 theme male 946:949 arg1 mice 969:972 young male and female βOGAKO mice 940:972 young male and female βOGAKO mice 940:972 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 3 10 from diabetes 503:510 arg1 mice 515:518 mice 515:518 mice 515:518 Previous work showed that OGT is highly expressed in the pancreas, and we demonstrated that hypo-O-GlcNAcylation in β-cells cause severe diabetes in mice. 36387851 2 11 theme O-GlcNAcase 301:311 arg1 enzyme 319:324 O-GlcNAcase (OGA) enzyme 301:324 O-GlcNAcase (OGA) enzyme 301:324 The addition of an O-GlcNAc molecule to proteins is catalyzed by O-GlcNAc transferase (OGT), whereas O-GlcNAcase (OGA) enzyme is responsible for removal of this PTM. 36387851 4 12 theme β-cell 589:594 arg1 health 596:601 β-cell health 589:601 β-cell health 589:601 These studies show a direct link between nutrient-sensitive OGT and β-cell health and function. 36387851 13 13 theme OGA 1688:1690 arg1 loss 1680:1683 the loss 1676:1683 the loss of OGA in β-cells 1676:1701 Taken together, these data demonstrate that the loss of OGA in β-cells reduces β-cell function, thereby perturbing glucose homeostasis. 36387851 9 14 theme insulin 1176:1182 arg1 content 1184:1190 Total insulin content 1170:1190 Total insulin content 1170:1190 Total insulin content was reduced despite an increase in pro-insulin to insulin ratio in βOGAKO islets. 36387851 14 15 theme OGT 1884:1886 arg1 loss 1888:1891 OGT loss 1884:1891 OGT loss 1884:1891 The findings reinforce the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell. 36387851 9 16 from increase 1215:1222 arg1 pro-insulin 1227:1237 pro-insulin 1227:1237 pro-insulin to insulin ratio in βOGAKO islets 1227:1271 Total insulin content was reduced despite an increase in pro-insulin to insulin ratio in βOGAKO islets. 36387851 13 17 from loss 1680:1683 arg1 β-cells 1695:1701 β-cells 1695:1701 β-cells 1695:1701 Taken together, these data demonstrate that the loss of OGA in β-cells reduces β-cell function, thereby perturbing glucose homeostasis. 36387851 14 18 theme rheostat 1795:1802 arg1 model 1804:1808 the rheostat model 1791:1808 the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell 1791:1943 The findings reinforce the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell. 36387851 10 19 theme βOGAKO 1274:1279 arg1 mice 1281:1284 βOGAKO mice 1274:1284 βOGAKO mice 1274:1284 βOGAKO mice showed deficit in insulin secretion in vivo and in vitro. 36387851 14 20 theme OGA 1859:1861 arg1 much 1853:1856 much 1853:1856 much 1853:1856 The findings reinforce the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell. 36387851 14 20 theme OGA 1859:1861 arg1 loss 1863:1866 OGA loss 1859:1866 OGA loss 1859:1866 The findings reinforce the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell. 36387851 8 21 theme littermate 1149:1158 arg1 controls 1160:1167 littermate controls 1149:1167 littermate controls 1149:1167 No alteration in β-cell mass was observed between βOGAKO and littermate controls. 36387851 3 22 from hypo-O-GlcNAcylation 458:477 arg1 β-cells 482:488 β-cells 482:488 β-cells 482:488 Previous work showed that OGT is highly expressed in the pancreas, and we demonstrated that hypo-O-GlcNAcylation in β-cells cause severe diabetes in mice. 36387851 1 23 theme Protein 94:100 arg1 modification 180:191 a nutrient and stress-sensitive protein post-translational modification 121:191 a nutrient and stress-sensitive protein post-translational modification (PTM) 121:197 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 1 23 theme Protein 94:100 arg1 O-GlcNAcylation 102:116 Protein O-GlcNAcylation 94:116 Protein O-GlcNAcylation 94:116 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 0 24 theme β-cell 11:16 arg1 hyper-O-GlcNAcylation 18:38 Pancreatic β-cell hyper-O-GlcNAcylation 0:38 Pancreatic β-cell hyper-O-GlcNAcylation 0:38 Pancreatic β-cell hyper-O-GlcNAcylation leads to impaired glucose homeostasis in vivo. 36387851 9 25 theme βOGAKO 1259:1264 arg1 islets 1266:1271 βOGAKO islets 1259:1271 βOGAKO islets 1259:1271 Total insulin content was reduced despite an increase in pro-insulin to insulin ratio in βOGAKO islets. 36387851 5 26 theme current 624:630 arg1 study 632:636 the current study 620:636 the current study 620:636 In the current study, we hypothesized that hyper-O-GlcNAcylation may confer protection from β-cell failure in high-fat diet (HFD)-induced obesity. 36387851 7 27 theme chow 929:932 arg1 diet 934:937 normal chow diet 922:937 normal chow diet 922:937 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 11 28 theme male 1398:1401 arg1 mice 1421:1424 both male and female βOGAKO mice 1393:1424 both male and female βOGAKO mice 1393:1424 When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. 36387851 9 29 from ratio 1250:1254 arg1 islets 1266:1271 βOGAKO islets 1259:1271 βOGAKO islets 1259:1271 Total insulin content was reduced despite an increase in pro-insulin to insulin ratio in βOGAKO islets. 36387851 0 30 theme Pancreatic 0:9 arg1 hyper-O-GlcNAcylation 18:38 Pancreatic β-cell hyper-O-GlcNAcylation 0:38 Pancreatic β-cell hyper-O-GlcNAcylation 0:38 Pancreatic β-cell hyper-O-GlcNAcylation leads to impaired glucose homeostasis in vivo. 36387851 4 31 theme direct 542:547 arg1 link 549:552 a direct link 540:552 a direct link between nutrient-sensitive OGT and β-cell health and function 540:614 These studies show a direct link between nutrient-sensitive OGT and β-cell health and function. 36387851 7 32 theme littermate 1067:1076 arg1 controls 1078:1085 littermate controls 1067:1085 littermate controls 1067:1085 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 9 33 theme insulin 1242:1248 arg1 ratio 1250:1254 insulin ratio 1242:1254 insulin ratio in βOGAKO islets 1242:1271 Total insulin content was reduced despite an increase in pro-insulin to insulin ratio in βOGAKO islets. 36387851 10 34 theme insulin 1304:1310 arg1 secretion 1312:1320 insulin secretion 1304:1320 insulin secretion 1304:1320 βOGAKO mice showed deficit in insulin secretion in vivo and in vitro. 36387851 3 35 theme Previous 366:373 arg1 work 375:378 Previous work 366:378 Previous work 366:378 Previous work showed that OGT is highly expressed in the pancreas, and we demonstrated that hypo-O-GlcNAcylation in β-cells cause severe diabetes in mice. 36387851 11 36 theme longer 1535:1540 arg1 exposure 1542:1549 longer exposure 1535:1549 longer exposure to HFD 1535:1556 When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. 36387851 2 37 theme OGA 314:316 arg1 enzyme 319:324 O-GlcNAcase (OGA) enzyme 301:324 O-GlcNAcase (OGA) enzyme 301:324 The addition of an O-GlcNAc molecule to proteins is catalyzed by O-GlcNAc transferase (OGT), whereas O-GlcNAcase (OGA) enzyme is responsible for removal of this PTM. 36387851 11 38 theme normal 1436:1441 arg1 gain 1455:1458 normal body weight gain 1436:1458 normal body weight gain 1436:1458 When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. 36387851 6 39 with model 810:814 arg1 βOGAKO 855:860 βOGAKO 855:860 βOGAKO 855:860 To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. 36387851 6 39 with model 810:814 arg1 ablation 845:852 constitutive β-cell OGA ablation 821:852 constitutive β-cell OGA ablation (βOGAKO) 821:861 To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. 36387851 14 40 theme intracellular 1813:1825 arg1 O-GlcNAcylation 1827:1841 intracellular O-GlcNAcylation 1813:1841 intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell 1813:1943 The findings reinforce the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell. 36387851 5 41 theme β-cell 709:714 arg1 failure 716:722 β-cell failure 709:722 β-cell failure 709:722 In the current study, we hypothesized that hyper-O-GlcNAcylation may confer protection from β-cell failure in high-fat diet (HFD)-induced obesity. 36387851 1 42 theme nutrient 123:130 arg1 PTM 194:196 PTM 194:196 PTM 194:196 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 1 42 theme nutrient 123:130 arg1 O-GlcNAcylation 102:116 Protein O-GlcNAcylation 94:116 Protein O-GlcNAcylation 94:116 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 1 42 theme nutrient 123:130 arg1 modification 180:191 a nutrient and stress-sensitive protein post-translational modification 121:191 a nutrient and stress-sensitive protein post-translational modification (PTM) 121:197 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 11 43 theme βOGAKO 1414:1419 arg1 mice 1421:1424 both male and female βOGAKO mice 1393:1424 both male and female βOGAKO mice 1393:1424 When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. 36387851 0 44 theme impaired 49:56 arg1 homeostasis 66:76 impaired glucose homeostasis 49:76 impaired glucose homeostasis 49:76 Pancreatic β-cell hyper-O-GlcNAcylation leads to impaired glucose homeostasis in vivo. 36387851 11 45 theme female 1407:1412 arg1 mice 1421:1424 both male and female βOGAKO mice 1393:1424 both male and female βOGAKO mice 1393:1424 When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. 36387851 12 46 theme littermate 1611:1620 arg1 controls 1622:1629 littermate controls 1611:1629 littermate controls 1611:1629 Comparable β-cell mass was found between βOGAKO and littermate controls. 36387851 11 47 theme young 1356:1360 arg1 animals 1362:1368 young animals 1356:1368 young animals 1356:1368 When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. 36387851 6 48 theme OGA 841:843 arg1 βOGAKO 855:860 βOGAKO 855:860 βOGAKO 855:860 To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. 36387851 6 48 theme OGA 841:843 arg1 ablation 845:852 constitutive β-cell OGA ablation 821:852 constitutive β-cell OGA ablation (βOGAKO) 821:861 To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. 36387851 7 49 theme glucose 991:997 arg1 tolerance 999:1007 normal glucose tolerance 984:1007 normal glucose tolerance 984:1007 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 2 50 dep catalyzed 252:260 arg1 whereas 293:299 whereas 293:299 whereas 293:299 The addition of an O-GlcNAc molecule to proteins is catalyzed by O-GlcNAc transferase (OGT), whereas O-GlcNAcase (OGA) enzyme is responsible for removal of this PTM. 36387851 13 51 theme glucose 1747:1753 arg1 homeostasis 1755:1765 glucose homeostasis 1747:1765 glucose homeostasis 1747:1765 Taken together, these data demonstrate that the loss of OGA in β-cells reduces β-cell function, thereby perturbing glucose homeostasis. 36387851 7 52 theme glucose 1023:1029 arg1 intolerance 1031:1041 developed glucose intolerance 1013:1041 developed glucose intolerance 1013:1041 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 6 53 theme β-cell 834:839 arg1 βOGAKO 855:860 βOGAKO 855:860 βOGAKO 855:860 To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. 36387851 6 53 theme β-cell 834:839 arg1 ablation 845:852 constitutive β-cell OGA ablation 821:852 constitutive β-cell OGA ablation (βOGAKO) 821:861 To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. 36387851 0 54 theme glucose 58:64 arg1 homeostasis 66:76 impaired glucose homeostasis 49:76 impaired glucose homeostasis 49:76 Pancreatic β-cell hyper-O-GlcNAcylation leads to impaired glucose homeostasis in vivo. 36387851 12 55 theme β-cell 1570:1575 arg1 mass 1577:1580 Comparable β-cell mass 1559:1580 Comparable β-cell mass 1559:1580 Comparable β-cell mass was found between βOGAKO and littermate controls. 36387851 6 56 theme constitutive 821:832 arg1 βOGAKO 855:860 βOGAKO 855:860 βOGAKO 855:860 To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. 36387851 6 56 theme constitutive 821:832 arg1 ablation 845:852 constitutive β-cell OGA ablation 821:852 constitutive β-cell OGA ablation (βOGAKO) 821:861 To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. 36387851 7 57 theme normal 922:927 arg1 diet 934:937 normal chow diet 922:937 normal chow diet 922:937 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 1 58 theme stress-sensitive 136:151 arg1 PTM 194:196 PTM 194:196 PTM 194:196 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 1 58 theme stress-sensitive 136:151 arg1 O-GlcNAcylation 102:116 Protein O-GlcNAcylation 94:116 Protein O-GlcNAcylation 94:116 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 1 58 theme stress-sensitive 136:151 arg1 modification 180:191 a nutrient and stress-sensitive protein post-translational modification 121:191 a nutrient and stress-sensitive protein post-translational modification (PTM) 121:197 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 12 59 theme Comparable 1559:1568 arg1 mass 1577:1580 Comparable β-cell mass 1559:1580 Comparable β-cell mass 1559:1580 Comparable β-cell mass was found between βOGAKO and littermate controls. 36387851 8 60 theme β-cell 1105:1110 arg1 mass 1112:1115 β-cell mass 1105:1115 β-cell mass 1105:1115 No alteration in β-cell mass was observed between βOGAKO and littermate controls. 36387851 2 61 theme molecule 228:235 arg1 addition 204:211 The addition 200:211 The addition of an O-GlcNAc molecule to proteins 200:247 The addition of an O-GlcNAc molecule to proteins is catalyzed by O-GlcNAc transferase (OGT), whereas O-GlcNAcase (OGA) enzyme is responsible for removal of this PTM. 36387851 11 62 theme glucose 1496:1502 arg1 intolerance 1504:1514 glucose intolerance 1496:1514 glucose intolerance that worsened with longer exposure to HFD 1496:1556 When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. 36387851 7 63 theme normal 984:989 arg1 tolerance 999:1007 normal glucose tolerance 984:1007 normal glucose tolerance 984:1007 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 1 64 theme protein 153:159 arg1 PTM 194:196 PTM 194:196 PTM 194:196 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 1 64 theme protein 153:159 arg1 O-GlcNAcylation 102:116 Protein O-GlcNAcylation 94:116 Protein O-GlcNAcylation 94:116 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 1 64 theme protein 153:159 arg1 modification 180:191 a nutrient and stress-sensitive protein post-translational modification 121:191 a nutrient and stress-sensitive protein post-translational modification (PTM) 121:197 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 14 65 theme little 1876:1881 arg1 O-GlcNAcylation 1894:1908 too little (OGT loss) O-GlcNAcylation 1872:1908 too little (OGT loss) O-GlcNAcylation 1872:1908 The findings reinforce the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell. 36387851 8 66 from alteration 1091:1100 arg1 mass 1112:1115 β-cell mass 1105:1115 β-cell mass 1105:1115 No alteration in β-cell mass was observed between βOGAKO and littermate controls. 36387851 7 67 theme developed 1013:1021 arg1 intolerance 1031:1041 developed glucose intolerance 1013:1041 developed glucose intolerance 1013:1041 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 2 68 theme O-GlcNAc 219:226 arg1 molecule 228:235 an O-GlcNAc molecule 216:235 an O-GlcNAc molecule 216:235 The addition of an O-GlcNAc molecule to proteins is catalyzed by O-GlcNAc transferase (OGT), whereas O-GlcNAcase (OGA) enzyme is responsible for removal of this PTM. 36387851 7 69 theme βOGAKO 962:967 arg1 mice 969:972 young male and female βOGAKO mice 940:972 young male and female βOGAKO mice 940:972 Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. 36387851 1 70 theme post-translational 161:178 arg1 PTM 194:196 PTM 194:196 PTM 194:196 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 1 70 theme post-translational 161:178 arg1 O-GlcNAcylation 102:116 Protein O-GlcNAcylation 94:116 Protein O-GlcNAcylation 94:116 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 1 70 theme post-translational 161:178 arg1 modification 180:191 a nutrient and stress-sensitive protein post-translational modification 121:191 a nutrient and stress-sensitive protein post-translational modification (PTM) 121:197 Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). 36387851 11 71 theme body 1443:1446 arg1 gain 1455:1458 normal body weight gain 1436:1458 normal body weight gain 1436:1458 When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. 36387851 6 72 from O-GlcNAcylation 888:902 arg1 β-cells 907:913 β-cells 907:913 β-cells 907:913 To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. 36387851 6 73 theme mouse 804:808 arg1 model 810:814 a mouse model 802:814 a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells 802:913 To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. 36387851 14 74 dep little 1876:1881 arg1 loss 1888:1891 OGT loss 1884:1891 OGT loss 1884:1891 The findings reinforce the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell. 36387851 14 75 theme O-GlcNAcylation 1827:1841 arg1 model 1804:1808 the rheostat model 1791:1808 the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell 1791:1943 The findings reinforce the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell. 36387851 11 76 theme weight 1448:1453 arg1 gain 1455:1458 normal body weight gain 1436:1458 normal body weight gain 1436:1458 When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. 36387851 5 77 theme -induced 746:753 arg1 obesity 755:761 high-fat diet (HFD)-induced obesity 727:761 high-fat diet (HFD)-induced obesity 727:761 In the current study, we hypothesized that hyper-O-GlcNAcylation may confer protection from β-cell failure in high-fat diet (HFD)-induced obesity. 36387851 2 78 theme O-GlcNAc 265:272 arg1 transferase 274:284 O-GlcNAc transferase 265:284 O-GlcNAc transferase (OGT) 265:290 The addition of an O-GlcNAc molecule to proteins is catalyzed by O-GlcNAc transferase (OGT), whereas O-GlcNAcase (OGA) enzyme is responsible for removal of this PTM. 36387851 2 78 theme O-GlcNAc 265:272 arg1 OGT 287:289 OGT 287:289 OGT 287:289 The addition of an O-GlcNAc molecule to proteins is catalyzed by O-GlcNAc transferase (OGT), whereas O-GlcNAcase (OGA) enzyme is responsible for removal of this PTM. 36387851 2 79 theme PTM 361:363 arg1 removal 345:351 removal 345:351 removal of this PTM 345:363 The addition of an O-GlcNAc molecule to proteins is catalyzed by O-GlcNAc transferase (OGT), whereas O-GlcNAcase (OGA) enzyme is responsible for removal of this PTM. 37258040 7 0 with mutant 1193:1198 arg1 affinity 1220:1227 30-fold higher affinity 1205:1227 30-fold higher affinity 1205:1227 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 7 0 with mutant 1193:1198 arg1 affinity 1254:1261 lower affinity 1248:1261 lower affinity 1248:1261 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 14 1 theme syngeneic 2361:2369 arg1 system 2388:2393 a syngeneic, immunocompetent system 2359:2393 a syngeneic, immunocompetent system 2359:2393 Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system. 37258040 3 2 theme solid 510:514 arg1 tumors 516:521 disseminated solid tumors 497:521 disseminated solid tumors in female C57BL/6J mice 497:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 2 3 from difficult 303:311 arg1 contrast 243:250 contrast 243:250 contrast 243:250 In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve. 37258040 4 4 link O-linked 678:685 arg1 glycosylation 687:699 aberrant O-linked glycosylation 669:699 aberrant O-linked glycosylation 669:699 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 10 5 theme effective 1578:1586 arg1 CARs 1588:1591 The most effective CARs 1569:1591 The most effective CARs 1569:1591 The most effective CARs exhibited the highest affinity for antigen. 37258040 13 6 theme ovarian 2132:2138 arg1 cancer 2140:2145 established ovarian cancer 2120:2145 established ovarian cancer 2120:2145 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 5 7 theme CARs 796:799 arg1 efficacy 766:773 The efficacy 762:773 The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen 762:835 The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. 37258040 14 8 theme tumor-bearing 2337:2349 arg1 mice 2351:2354 tumor-bearing mice 2337:2354 tumor-bearing mice 2337:2354 Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system. 37258040 2 9 theme solid 281:285 arg1 tumors 287:292 solid tumors 281:292 solid tumors 281:292 In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve. 37258040 1 10 theme antigen 173:179 arg1 CAR 191:193 CAR 191:193 CAR 191:193 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. 37258040 1 10 theme antigen 173:179 arg1 receptor 181:188 a chimeric antigen receptor 162:188 a chimeric antigen receptor (CAR) against CD19 162:207 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. 37258040 4 11 theme antibody 589:596 arg1 237 598:600 antibody 237 589:600 antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc 589:759 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 11 12 theme macrophages 1726:1736 arg1 numbers 1703:1709 increased numbers 1693:1709 increased numbers of T cells and macrophages 1693:1736 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 11 12 theme macrophages 1726:1736 arg1 levels 1750:1755 higher levels 1743:1755 higher levels of cleaved caspase-3 1743:1776 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 7 13 with CARs 1238:1241 arg1 affinity 1220:1227 30-fold higher affinity 1205:1227 30-fold higher affinity 1205:1227 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 7 13 with CARs 1238:1241 arg1 affinity 1254:1261 lower affinity 1248:1261 lower affinity 1248:1261 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 13 14 theme potential 2096:2104 arg1 treatment 2106:2114 a potential treatment 2094:2114 a potential treatment for established ovarian cancer 2094:2145 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 13 14 theme potential 2096:2104 arg1 development 2045:2055 the development 2041:2055 the development of affinity-optimized CAR-T cells 2041:2089 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 14 15 theme toxicity 2325:2332 arg1 evidence 2313:2320 no evidence 2310:2320 no evidence of toxicity 2310:2332 Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system. 37258040 11 16 theme cleaved 1760:1766 arg1 caspase-3 1768:1776 cleaved caspase-3 1760:1776 cleaved caspase-3 1760:1776 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 12 17 theme cytokine 1915:1922 arg1 expression 1924:1933 antigen-independent cytokine expression 1895:1933 antigen-independent cytokine expression 1895:1933 Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. 37258040 8 18 theme intraperitoneal 1387:1401 arg1 administration 1403:1416 intraperitoneal administration 1387:1416 intraperitoneal administration 1387:1416 Tumor regression could be achieved with a single intravenous dose of the CARs, but intraperitoneal administration was even more effective. 37258040 4 19 theme O-linked 678:685 arg1 glycosylation 687:699 aberrant O-linked glycosylation 669:699 aberrant O-linked glycosylation 669:699 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 13 20 theme CAR-T 2079:2083 arg1 cells 2085:2089 affinity-optimized CAR-T cells 2060:2089 affinity-optimized CAR-T cells 2060:2089 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 6 21 with line 950:953 arg1 observations 965:976 many observations 960:976 many observations about the impact of aberrant O-linked glycosylation 960:1028 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 11 22 theme increased 1693:1701 arg1 numbers 1703:1709 increased numbers 1693:1709 increased numbers of T cells and macrophages 1693:1736 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 3 23 theme disseminated 497:508 arg1 tumors 516:521 disseminated solid tumors 497:521 disseminated solid tumors in female C57BL/6J mice 497:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 1 24 theme cancers 128:134 arg1 Treatment 104:112 BACKGROUND Treatment 93:112 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 93:207 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. 37258040 1 25 theme blood 122:126 arg1 cancers 128:134 some blood cancers 117:134 some blood cancers 117:134 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. 37258040 7 26 theme ID8Cosmc-KO 1284:1294 arg1 tumors 1296:1301 advanced ID8Cosmc-KO tumors 1275:1301 advanced ID8Cosmc-KO tumors 1275:1301 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 0 27 theme cell 13:16 arg1 treatment 18:26 Single CAR-T cell treatment 0:26 Single CAR-T cell treatment 0:26 Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model. 37258040 5 28 theme cytoplasmic 868:878 arg1 domains 880:886 CD28/CD3ζ cytoplasmic domains 858:886 CD28/CD3ζ cytoplasmic domains 858:886 The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. 37258040 11 29 theme cells 1716:1720 arg1 numbers 1703:1709 increased numbers 1693:1709 increased numbers of T cells and macrophages 1693:1736 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 11 29 theme cells 1716:1720 arg1 levels 1750:1755 higher levels 1743:1755 higher levels of cleaved caspase-3 1743:1776 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 0 30 theme syngeneic 70:78 arg1 model 86:90 a syngeneic mouse model 68:90 a syngeneic mouse model 68:90 Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model. 37258040 12 31 contain had 1942:1944 arg1 it 1939:1940 it 1939:1940 it 1939:1940 Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. 37258040 12 31 contain had 1942:1944 arg2 levels 1953:1958 higher levels 1946:1958 higher levels of the immunosuppressive cytokine interleukin10 1946:2006 Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. 37258040 4 32 theme chaperone 745:753 arg1 Cosmc 755:759 the transferase-dependent chaperone Cosmc 719:759 the transferase-dependent chaperone Cosmc 719:759 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 14 33 theme Tn-dependent 2278:2289 arg1 cells 2297:2301 the most potent Tn-dependent CAR-T cells 2262:2301 the most potent Tn-dependent CAR-T cells 2262:2301 Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system. 37258040 2 34 theme CAR-T 253:257 arg1 efficacy 264:271 CAR-T cell efficacy 253:271 CAR-T cell efficacy against solid tumors 253:292 In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve. 37258040 9 35 theme months 1486:1491 arg1 period 1476:1481 a period 1474:1481 a period of months 1474:1491 The CAR-T cells persisted over a period of months, allowing CAR-treated mice to delay tumor growth in a re-challenge setting. 37258040 7 36 theme lower 1248:1252 arg1 affinity 1254:1261 lower affinity 1248:1261 lower affinity 1248:1261 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 8 37 theme Tumor 1304:1308 arg1 regression 1310:1319 Tumor regression 1304:1319 Tumor regression 1304:1319 Tumor regression could be achieved with a single intravenous dose of the CARs, but intraperitoneal administration was even more effective. 37258040 6 38 theme ID8Cosmc 1035:1042 arg1 line 950:953 line 950:953 line with many observations about the impact of aberrant O-linked glycosylation 950:1028 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 6 38 theme ID8Cosmc 1035:1042 arg1 ID8Cosmc-KO 1055:1065 ID8Cosmc-KO 1055:1065 ID8Cosmc-KO 1055:1065 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 6 38 theme ID8Cosmc 1035:1042 arg1 knock-out 1044:1052 the ID8Cosmc knock-out 1031:1052 the ID8Cosmc knock-out (ID8Cosmc-KO) 1031:1066 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 3 39 theme ovarian 391:397 arg1 cancers 399:405 ovarian cancers 391:405 ovarian cancers 391:405 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 0 40 theme Single 0:5 arg1 treatment 18:26 Single CAR-T cell treatment 0:26 Single CAR-T cell treatment 0:26 Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model. 37258040 7 41 with CAR 1183:1185 arg1 affinity 1220:1227 30-fold higher affinity 1205:1227 30-fold higher affinity 1205:1227 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 7 41 with CAR 1183:1185 arg1 affinity 1254:1261 lower affinity 1248:1261 lower affinity 1248:1261 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 3 42 theme mouse 420:424 arg1 line 446:449 the mouse ovarian cancer cell line 416:449 the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice 416:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 5 43 theme varying 806:812 arg1 affinity 814:821 varying affinity 806:821 varying affinity to Tn antigen 806:835 The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. 37258040 13 44 theme cytokine 2222:2229 arg1 release 2231:2237 inflammatory cytokine release 2209:2237 inflammatory cytokine release in vitro 2209:2246 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 6 45 theme O-linked 1007:1014 arg1 glycosylation 1016:1028 aberrant O-linked glycosylation 998:1028 aberrant O-linked glycosylation 998:1028 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 3 46 theme treatments 372:381 arg1 potential 348:356 the potential 344:356 the potential of CAR-T cell treatments against ovarian cancers 344:405 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 6 47 from RESULTS 939:945 arg1 line 950:953 line 950:953 line with many observations about the impact of aberrant O-linked glycosylation 950:1028 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 6 47 from RESULTS 939:945 arg1 knock-out 1044:1052 the ID8Cosmc knock-out 1031:1052 the ID8Cosmc knock-out (ID8Cosmc-KO) 1031:1066 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 7 48 theme enhanced 1148:1155 arg1 growth 1163:1168 the enhanced tumor growth 1144:1168 the enhanced tumor growth in vivo 1144:1176 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 10 49 theme highest 1607:1613 arg1 affinity 1615:1622 the highest affinity 1603:1622 the highest affinity for antigen 1603:1634 The most effective CARs exhibited the highest affinity for antigen. 37258040 3 50 theme CAR-T 361:365 arg1 treatments 372:381 CAR-T cell treatments 361:381 CAR-T cell treatments against ovarian cancers 361:405 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 8 51 theme intravenous 1353:1363 arg1 dose 1365:1368 a single intravenous dose 1344:1368 a single intravenous dose of the CARs 1344:1380 Tumor regression could be achieved with a single intravenous dose of the CARs, but intraperitoneal administration was even more effective. 37258040 0 52 theme ovarian 50:56 arg1 cancer 58:63 disseminated ovarian cancer 37:63 disseminated ovarian cancer 37:63 Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model. 37258040 13 53 theme distinct 2189:2196 arg1 pattern 2198:2204 a distinct pattern 2187:2204 a distinct pattern of inflammatory cytokine release in vitro 2187:2246 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 6 54 theme tumor 1089:1093 arg1 progression 1095:1105 more rapid tumor progression 1078:1105 more rapid tumor progression 1078:1105 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 3 55 theme cancer 434:439 arg1 line 446:449 the mouse ovarian cancer cell line 416:449 the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice 416:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 1 56 theme T 141:141 arg1 cells 143:147 T cells 141:147 T cells that express a chimeric antigen receptor (CAR) against CD19 141:207 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. 37258040 8 57 theme CARs 1377:1380 arg1 dose 1365:1368 a single intravenous dose 1344:1368 a single intravenous dose of the CARs 1344:1380 Tumor regression could be achieved with a single intravenous dose of the CARs, but intraperitoneal administration was even more effective. 37258040 3 58 theme intraperitoneal 461:475 arg1 model 477:481 an intraperitoneal model 458:481 an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice 458:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 13 59 theme effective 2162:2170 arg1 CARs 2172:2175 the most effective CARs 2153:2175 the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro 2153:2246 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 12 60 theme immunosuppressive 1967:1983 arg1 interleukin10 1994:2006 the immunosuppressive cytokine interleukin10 1963:2006 the immunosuppressive cytokine interleukin10 1963:2006 Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. 37258040 4 61 theme single-chain 568:579 arg1 Fv 581:582 a single-chain Fv 566:582 a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc 566:759 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 1 62 theme remarkable 220:229 arg1 results 231:237 remarkable results 220:237 remarkable results 220:237 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. 37258040 12 63 theme interleukin10 1994:2006 arg1 levels 1953:1958 higher levels 1946:1958 higher levels of the immunosuppressive cytokine interleukin10 1946:2006 Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. 37258040 2 64 theme cell 259:262 arg1 efficacy 264:271 CAR-T cell efficacy 253:271 CAR-T cell efficacy against solid tumors 253:292 In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve. 37258040 12 65 theme higher 1946:1951 arg1 levels 1953:1958 higher levels 1946:1958 higher levels of the immunosuppressive cytokine interleukin10 1946:2006 Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. 37258040 3 66 from model 477:481 arg1 ID8 451:453 ID8 451:453 ID8 451:453 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 6 67 link O-linked 1007:1014 arg1 glycosylation 1016:1028 aberrant O-linked glycosylation 998:1028 aberrant O-linked glycosylation 998:1028 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 3 68 theme female 526:531 arg1 mice 542:545 female C57BL/6J mice 526:545 female C57BL/6J mice 526:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 1 69 theme chimeric 164:171 arg1 CAR 191:193 CAR 191:193 CAR 191:193 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. 37258040 1 69 theme chimeric 164:171 arg1 receptor 181:188 a chimeric antigen receptor 162:188 a chimeric antigen receptor (CAR) against CD19 162:207 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. 37258040 1 70 with Treatment 104:112 arg1 cells 143:147 T cells 141:147 T cells that express a chimeric antigen receptor (CAR) against CD19 141:207 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. 37258040 6 71 theme wild-type 1121:1129 arg1 ID8 1131:1133 wild-type ID8 1121:1133 wild-type ID8 1121:1133 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 11 72 theme higher 1743:1748 arg1 levels 1750:1755 higher levels 1743:1755 higher levels of cleaved caspase-3 1743:1776 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 3 73 from ID8 451:453 arg1 model 477:481 an intraperitoneal model 458:481 an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice 458:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 4 74 from 237 598:600 arg1 Fv 581:582 a single-chain Fv 566:582 a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc 566:759 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 3 75 theme C57BL/6J 533:540 arg1 mice 542:545 female C57BL/6J mice 526:545 female C57BL/6J mice 526:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 5 76 with CARs 796:799 arg1 affinity 814:821 varying affinity 806:821 varying affinity to Tn antigen 806:835 The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. 37258040 11 77 theme tumor 1786:1790 arg1 microenvironment 1792:1807 the tumor microenvironment 1782:1807 the tumor microenvironment 1782:1807 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 5 78 theme Tn 826:827 arg1 antigen 829:835 Tn antigen 826:835 Tn antigen 826:835 The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. 37258040 11 79 theme caspase-3 1768:1776 arg1 numbers 1703:1709 increased numbers 1693:1709 increased numbers of T cells and macrophages 1693:1736 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 11 79 theme caspase-3 1768:1776 arg1 levels 1750:1755 higher levels 1743:1755 higher levels of cleaved caspase-3 1743:1776 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 13 80 theme established 2120:2130 arg1 cancer 2140:2145 established ovarian cancer 2120:2145 established ovarian cancer 2120:2145 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 12 81 theme antigen-independent 1895:1913 arg1 expression 1924:1933 antigen-independent cytokine expression 1895:1933 antigen-independent cytokine expression 1895:1933 Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. 37258040 4 82 theme aberrant 669:676 arg1 glycosylation 687:699 aberrant O-linked glycosylation 669:699 aberrant O-linked glycosylation 669:699 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 3 83 from tumors 516:521 arg1 mice 542:545 female C57BL/6J mice 526:545 female C57BL/6J mice 526:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 13 84 theme cells 2085:2089 arg1 development 2045:2055 the development 2041:2055 the development of affinity-optimized CAR-T cells 2041:2089 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 13 84 theme cells 2085:2089 arg1 treatment 2106:2114 a potential treatment 2094:2114 a potential treatment for established ovarian cancer 2094:2145 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 9 85 theme CAR-T 1447:1451 arg1 cells 1453:1457 The CAR-T cells 1443:1457 The CAR-T cells 1443:1457 The CAR-T cells persisted over a period of months, allowing CAR-treated mice to delay tumor growth in a re-challenge setting. 37258040 2 86 from contrast 243:250 arg1 difficult 303:311 difficult 303:311 difficult 303:311 In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve. 37258040 6 87 theme rapid 1083:1087 arg1 progression 1095:1105 more rapid tumor progression 1078:1105 more rapid tumor progression 1078:1105 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 4 88 contain contained 556:564 arg2 Fv 581:582 a single-chain Fv 566:582 a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc 566:759 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 4 88 contain contained 556:564 arg1 CAR 552:554 The CAR 548:554 The CAR 548:554 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 0 89 theme mouse 80:84 arg1 model 86:90 a syngeneic mouse model 68:90 a syngeneic mouse model 68:90 Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model. 37258040 6 90 theme many 960:963 arg1 observations 965:976 many observations 960:976 many observations about the impact of aberrant O-linked glycosylation 960:1028 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 5 91 contain containing 847:856 arg1 each 842:845 each 842:845 each 842:845 The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. 37258040 5 91 contain containing 847:856 arg2 domains 880:886 CD28/CD3ζ cytoplasmic domains 858:886 CD28/CD3ζ cytoplasmic domains 858:886 The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. 37258040 12 92 theme tonic 1868:1872 arg1 signaling 1874:1882 tonic signaling 1868:1882 tonic signaling leading to antigen-independent cytokine expression 1868:1933 Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. 37258040 14 93 theme CAR-T 2291:2295 arg1 cells 2297:2301 the most potent Tn-dependent CAR-T cells 2262:2301 the most potent Tn-dependent CAR-T cells 2262:2301 Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system. 37258040 13 94 theme affinity-optimized 2060:2077 arg1 cells 2085:2089 affinity-optimized CAR-T cells 2060:2089 affinity-optimized CAR-T cells 2060:2089 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 4 95 theme transferase-dependent 723:743 arg1 Cosmc 755:759 the transferase-dependent chaperone Cosmc 719:759 the transferase-dependent chaperone Cosmc 719:759 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 14 96 theme potent 2271:2276 arg1 cells 2297:2301 the most potent Tn-dependent CAR-T cells 2262:2301 the most potent Tn-dependent CAR-T cells 2262:2301 Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system. 37258040 11 97 theme T 1714:1714 arg1 cells 1716:1720 T cells 1714:1720 T cells 1714:1720 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 7 98 theme tumor 1157:1161 arg1 growth 1163:1168 the enhanced tumor growth 1144:1168 the enhanced tumor growth in vivo 1144:1176 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 14 99 dep syngeneic 2361:2369 arg1 immunocompetent 2372:2386 immunocompetent 2372:2386 immunocompetent 2372:2386 Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system. 37258040 4 100 theme Cosmc 755:759 arg1 absence 708:714 the absence 704:714 the absence of the transferase-dependent chaperone Cosmc 704:759 The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. 37258040 0 101 theme CAR-T 7:11 arg1 treatment 18:26 Single CAR-T cell treatment 0:26 Single CAR-T cell treatment 0:26 Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model. 37258040 12 102 theme effective 1845:1853 arg1 CAR 1855:1857 the least therapeutically effective CAR 1819:1857 the least therapeutically effective CAR 1819:1857 Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. 37258040 9 103 theme CAR-treated 1503:1513 arg1 mice 1515:1518 CAR-treated mice 1503:1518 CAR-treated mice 1503:1518 The CAR-T cells persisted over a period of months, allowing CAR-treated mice to delay tumor growth in a re-challenge setting. 37258040 3 104 used used 411:414 arg2 we 408:409 we 408:409 we 408:409 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 13 105 theme inflammatory 2209:2220 arg1 release 2231:2237 inflammatory cytokine release 2209:2237 inflammatory cytokine release in vitro 2209:2246 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 1 106 theme BACKGROUND 93:102 arg1 Treatment 104:112 BACKGROUND Treatment 93:112 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 93:207 BACKGROUND Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. 37258040 6 107 theme glycosylation 1016:1028 arg1 impact 988:993 the impact 984:993 the impact of aberrant O-linked glycosylation 984:1028 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 11 108 theme Antitumor 1637:1645 arg1 effects 1647:1653 Antitumor effects 1637:1653 Antitumor effects observed in vivo 1637:1670 Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. 37258040 3 109 theme ovarian 426:432 arg1 line 446:449 the mouse ovarian cancer cell line 416:449 the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice 416:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 0 110 theme disseminated 37:48 arg1 cancer 58:63 disseminated ovarian cancer 37:63 disseminated ovarian cancer 37:63 Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model. 37258040 13 111 theme release 2231:2237 arg1 pattern 2198:2204 a distinct pattern 2187:2204 a distinct pattern of inflammatory cytokine release in vitro 2187:2246 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 9 112 theme tumor 1529:1533 arg1 growth 1535:1540 tumor growth 1529:1540 tumor growth 1529:1540 The CAR-T cells persisted over a period of months, allowing CAR-treated mice to delay tumor growth in a re-challenge setting. 37258040 6 113 theme aberrant 998:1005 arg1 glycosylation 1016:1028 aberrant O-linked glycosylation 998:1028 aberrant O-linked glycosylation 998:1028 RESULTS In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. 37258040 3 114 theme cell 367:370 arg1 treatments 372:381 CAR-T cell treatments 361:381 CAR-T cell treatments against ovarian cancers 361:405 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 13 115 dep CONCLUSION 2009:2018 arg1 support 2033:2039 support 2033:2039 support 2033:2039 CONCLUSION The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. 37258040 8 116 theme single 1346:1351 arg1 dose 1365:1368 a single intravenous dose 1344:1368 a single intravenous dose of the CARs 1344:1380 Tumor regression could be achieved with a single intravenous dose of the CARs, but intraperitoneal administration was even more effective. 37258040 3 117 theme ID8 451:453 arg1 line 446:449 the mouse ovarian cancer cell line 416:449 the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice 416:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 9 118 theme re-challenge 1547:1558 arg1 setting 1560:1566 a re-challenge setting 1545:1566 a re-challenge setting 1545:1566 The CAR-T cells persisted over a period of months, allowing CAR-treated mice to delay tumor growth in a re-challenge setting. 37258040 7 119 theme higher 1213:1218 arg1 affinity 1220:1227 30-fold higher affinity 1205:1227 30-fold higher affinity 1205:1227 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 3 120 theme cell 441:444 arg1 line 446:449 the mouse ovarian cancer cell line 416:449 the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice 416:545 METHODS To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. 37258040 12 121 theme cytokine 1985:1992 arg1 interleukin10 1994:2006 the immunosuppressive cytokine interleukin10 1963:2006 the immunosuppressive cytokine interleukin10 1963:2006 Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. 37258040 7 122 theme advanced 1275:1282 arg1 tumors 1296:1301 advanced ID8Cosmc-KO tumors 1275:1301 advanced ID8Cosmc-KO tumors 1275:1301 Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. 37258040 5 123 theme Tn-dependent 783:794 arg1 CARs 796:799 four Tn-dependent CARs 778:799 four Tn-dependent CARs with varying affinity to Tn antigen 778:835 The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. 37183920 6 0 theme acid 1351:1354 arg1 activity 1377:1384 the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity 1296:1384 activity 1377:1384 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 5 1 theme triterpenes 1036:1046 arg1 content 1025:1031 The content 1021:1031 The content of triterpenes and polysaccharides 1021:1066 The content of triterpenes and polysaccharides increased, except for total phenol content. 37183920 8 2 dep G. 1726:1727 arg1 atrum 1729:1733 G. atrum 1726:1733 G. atrum 1726:1733 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 4 3 theme optimal 781:787 arg1 medium 789:794 the optimal medium 777:794 the optimal medium 777:794 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 8 4 theme bioactive 1567:1575 arg1 components 1577:1586 The main bioactive components 1558:1586 The main bioactive components of G. atrum 1558:1598 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 6 5 theme 3-ethylbenzothiazoline-6-sulfonic 1317:1349 arg1 activity 1377:1384 the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity 1296:1384 activity 1377:1384 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 4 6 dep juices 917:922 arg1 juice 969:973 simulated gastric digestive juice 941:973 simulated gastric digestive juice 941:973 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 4 6 dep juices 917:922 arg1 water 934:938 purified water 925:938 purified water 925:938 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 4 6 dep juices 917:922 arg1 juice 1013:1017 simulated gastrointestinal digestive juice 976:1017 simulated gastrointestinal digestive juice 976:1017 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 0 7 from Z19 59:61 arg1 Optimization 0:11 Optimization 0:11 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 0:198 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 0 7 from Z19 59:61 arg1 Yield 27:31 Triterpene Yield 16:31 Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) 16:78 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 8 8 theme main 1562:1565 arg1 components 1577:1586 The main bioactive components 1558:1586 The main bioactive components of G. atrum 1558:1598 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 1 9 theme response 368:375 arg1 methodology 385:395 response surface methodology 368:395 response surface methodology 368:395 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 1 9 theme response 368:375 arg1 optimization 272:283 optimization 272:283 optimization based on single-factor experiments 272:318 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 5 10 theme phenol 1096:1101 arg1 content 1103:1109 total phenol content 1090:1109 total phenol content 1090:1109 The content of triterpenes and polysaccharides increased, except for total phenol content. 37183920 8 11 theme digestive 1625:1633 arg1 juices 1635:1640 digestive juices 1625:1640 digestive juices 1625:1640 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 7 12 theme α-glucosidase 1489:1501 arg1 activity 1456:1463 the activity 1452:1463 the activity of α-amylase (α-AL) and α-glucosidase (α-GC) in the digestive juices 1452:1532 In terms of enzyme viability, the activity of α-amylase (α-AL) and α-glucosidase (α-GC) in the digestive juices decreased dramatically. 37183920 1 13 theme surface 377:383 arg1 methodology 385:395 response surface methodology 368:395 response surface methodology 368:395 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 1 13 theme surface 377:383 arg1 optimization 272:283 optimization 272:283 optimization based on single-factor experiments 272:318 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 6 14 theme 2,4,6-trinitrophenyl 1208:1227 arg1 activity 1259:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 0 15 theme Medium 99:104 arg1 Components 106:115 Medium Components 99:115 Medium Components 99:115 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 8 16 from components 1577:1586 arg1 juices 1635:1640 digestive juices 1625:1640 digestive juices 1625:1640 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 4 17 theme gastric 951:957 arg1 juice 969:973 simulated gastric digestive juice 941:973 simulated gastric digestive juice 941:973 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 4 17 theme gastric 951:957 arg1 water 934:938 purified water 925:938 purified water 925:938 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 6 18 theme scavenging 1366:1375 arg1 activity 1377:1384 the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity 1296:1384 activity 1377:1384 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 6 19 theme 1,1-diphenyl-2-picrylhydrazyl 1154:1182 arg1 activity 1259:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 0 20 theme atrum 48:52 arg1 Agaricomycetes 64:77 Agaricomycetes 64:77 Agaricomycetes 64:77 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 0 20 theme atrum 48:52 arg1 Z19 59:61 Ganoderma atrum HBSD Z19 38:61 Ganoderma atrum HBSD Z19 (Agaricomycetes) 38:78 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 3 21 theme optimal 600:606 arg1 conditions 608:617 the optimal conditions 596:617 the optimal conditions 596:617 Under the optimal conditions, the highest triterpene yield of 0.527 g·L-1 was obtained, which was 4.705-fold higher than before optimization. 37183920 4 22 theme digestive 907:915 arg1 juices 917:922 different digestive juices 897:922 different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice) 897:1018 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 6 23 theme radical 1184:1190 arg1 activity 1259:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 6 24 theme scavenging 1248:1257 arg1 activity 1259:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 8 25 from use 1698:1700 arg1 G. 1726:1727 G. 1726:1727 G. 1726:1727 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 4 26 theme purified 925:932 arg1 juice 969:973 simulated gastric digestive juice 941:973 simulated gastric digestive juice 941:973 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 4 26 theme purified 925:932 arg1 water 934:938 purified water 925:938 purified water 925:938 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 4 26 theme purified 925:932 arg1 juice 1013:1017 simulated gastrointestinal digestive juice 976:1017 simulated gastrointestinal digestive juice 976:1017 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 5 27 theme total 1090:1094 arg1 content 1103:1109 total phenol content 1090:1109 total phenol content 1090:1109 The content of triterpenes and polysaccharides increased, except for total phenol content. 37183920 4 28 theme fermented 736:744 arg1 powder 746:751 The fermented powder 732:751 The fermented powder that was collected from the optimal medium 732:794 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 6 29 dep activity 1377:1384 arg1 2'-azino-bis 1303:1314 the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity 1296:1384 2'-azino-bis 1303:1314 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 6 30 theme hydrazyl 1230:1237 arg1 activity 1259:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 0 31 theme Yield 27:31 arg1 Optimization 0:11 Optimization 0:11 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 0:198 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 1 32 theme single-factor 294:306 arg1 experiments 308:318 single-factor experiments 294:318 single-factor experiments 294:318 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 6 33 theme antioxidant 1128:1138 arg1 activity 1140:1147 the antioxidant activity 1124:1147 the antioxidant activity 1124:1147 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 2 34 theme optimal 445:451 arg1 g·L-1 473:477 g·L-1 473:477 g·L-1 473:477 The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. 37183920 2 34 theme optimal 445:451 arg1 glucose 484:490 glucose (46.0) 484:497 glucose (46.0) 484:497 The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. 37183920 2 34 theme optimal 445:451 arg1 composition 460:470 The optimal medium composition 441:470 The optimal medium composition (g·L-1) 441:478 The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. 37183920 0 35 theme Triterpene 16:25 arg1 Yield 27:31 Triterpene Yield 16:31 Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) 16:78 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 3 36 theme highest 624:630 arg1 yield 643:647 the highest triterpene yield 620:647 the highest triterpene yield of 0.527 g·L-1 620:662 Under the optimal conditions, the highest triterpene yield of 0.527 g·L-1 was obtained, which was 4.705-fold higher than before optimization. 37183920 0 37 theme Components 106:115 arg1 Optimization 83:94 Optimization 83:94 Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro 83:197 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 4 38 theme simulated 813:821 arg1 digestion 840:848 simulated gastrointestinal digestion 813:848 simulated gastrointestinal digestion 813:848 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 8 39 from bioactivity 1610:1620 arg1 juices 1635:1640 digestive juices 1625:1640 digestive juices 1625:1640 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 8 40 dep G. 1591:1592 arg1 atrum 1594:1598 G. atrum 1591:1598 G. atrum 1591:1598 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 1 41 theme intracellular 204:216 arg1 yield 229:233 The intracellular triterpene yield 200:233 The intracellular triterpene yield from Ganoderma atrum 200:254 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 0 42 theme Ganoderma 38:46 arg1 Agaricomycetes 64:77 Agaricomycetes 64:77 Agaricomycetes 64:77 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 0 42 theme Ganoderma 38:46 arg1 Z19 59:61 Ganoderma atrum HBSD Z19 38:61 Ganoderma atrum HBSD Z19 (Agaricomycetes) 38:78 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 3 43 theme triterpene 632:641 arg1 yield 643:647 the highest triterpene yield 620:647 the highest triterpene yield of 0.527 g·L-1 620:662 Under the optimal conditions, the highest triterpene yield of 0.527 g·L-1 was obtained, which was 4.705-fold higher than before optimization. 37183920 4 44 theme gastrointestinal 823:838 arg1 digestion 840:848 simulated gastrointestinal digestion 813:848 simulated gastrointestinal digestion 813:848 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 8 45 theme G. 1591:1592 arg1 components 1577:1586 The main bioactive components 1558:1586 The main bioactive components of G. atrum 1558:1598 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 8 45 theme G. 1591:1592 arg1 bioactivity 1610:1620 their bioactivity 1604:1620 their bioactivity in digestive juices 1604:1640 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 1 46 theme triterpene 218:227 arg1 yield 229:233 The intracellular triterpene yield 200:233 The intracellular triterpene yield from Ganoderma atrum 200:254 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 4 47 theme different 897:905 arg1 juices 917:922 different digestive juices 897:922 different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice) 897:1018 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 1 48 theme Plackett-Burman 321:335 arg1 optimization 272:283 optimization 272:283 optimization based on single-factor experiments 272:318 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 1 48 theme Plackett-Burman 321:335 arg1 PBED 358:361 PBED 358:361 PBED 358:361 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 1 48 theme Plackett-Burman 321:335 arg1 design 350:355 Plackett-Burman experimental design 321:355 Plackett-Burman experimental design (PBED) 321:362 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 1 48 theme Plackett-Burman 321:335 arg1 RSM 398:400 RSM 398:400 RSM 398:400 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 0 49 theme Evaluation 121:130 arg1 Optimization 83:94 Optimization 83:94 Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro 83:197 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 1 50 theme liquid 409:414 arg1 conditions 429:438 liquid fermentation conditions 409:438 liquid fermentation conditions 409:438 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 4 51 theme simulated 941:949 arg1 juice 969:973 simulated gastric digestive juice 941:973 simulated gastric digestive juice 941:973 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 4 51 theme simulated 941:949 arg1 water 934:938 purified water 925:938 purified water 925:938 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 2 52 theme cake 505:508 arg1 powder 510:515 bean cake powder 500:515 bean cake powder (30.2) 500:522 The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. 37183920 2 52 theme cake 505:508 arg1 30.2 518:521 30.2 518:521 30.2 518:521 The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. 37183920 0 53 theme HBSD 54:57 arg1 Agaricomycetes 64:77 Agaricomycetes 64:77 Agaricomycetes 64:77 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 0 53 theme HBSD 54:57 arg1 Z19 59:61 Ganoderma atrum HBSD Z19 38:61 Ganoderma atrum HBSD Z19 (Agaricomycetes) 38:78 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 1 54 theme experimental 337:348 arg1 optimization 272:283 optimization 272:283 optimization based on single-factor experiments 272:318 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 1 54 theme experimental 337:348 arg1 PBED 358:361 PBED 358:361 PBED 358:361 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 1 54 theme experimental 337:348 arg1 design 350:355 Plackett-Burman experimental design 321:355 Plackett-Burman experimental design (PBED) 321:362 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 1 54 theme experimental 337:348 arg1 RSM 398:400 RSM 398:400 RSM 398:400 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 1 55 from atrum 250:254 arg1 yield 229:233 The intracellular triterpene yield 200:233 The intracellular triterpene yield from Ganoderma atrum 200:254 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 1 56 theme fermentation 416:427 arg1 conditions 429:438 liquid fermentation conditions 409:438 liquid fermentation conditions 409:438 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 6 57 theme activity 1140:1147 arg1 terms 1115:1119 terms 1115:1119 terms of the antioxidant activity 1115:1147 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 8 58 theme effective 1688:1696 arg1 use 1698:1700 the effective use 1684:1700 the effective use of fermented power from G. atrum 1684:1733 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 8 59 from G. 1726:1727 arg1 use 1698:1700 the effective use 1684:1700 the effective use of fermented power from G. atrum 1684:1733 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 8 59 from G. 1726:1727 arg1 power 1715:1719 fermented power 1705:1719 fermented power from G. atrum 1705:1733 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 0 60 from Optimization 0:11 arg1 Agaricomycetes 64:77 Agaricomycetes 64:77 Agaricomycetes 64:77 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 0 60 from Optimization 0:11 arg1 Z19 59:61 Ganoderma atrum HBSD Z19 38:61 Ganoderma atrum HBSD Z19 (Agaricomycetes) 38:78 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 0 61 theme Bioactivity 135:145 arg1 Evaluation 121:130 Evaluation 121:130 Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro 121:197 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 0 61 theme Bioactivity 135:145 arg1 Components 106:115 Medium Components 99:115 Medium Components 99:115 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 6 62 theme 2,2-diphenyl-1- 1192:1206 arg1 activity 1259:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity 1150:1266 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 8 63 theme fermented 1705:1713 arg1 power 1715:1719 fermented power 1705:1719 fermented power from G. atrum 1705:1733 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 4 64 theme gastrointestinal 986:1001 arg1 water 934:938 purified water 925:938 purified water 925:938 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 4 64 theme gastrointestinal 986:1001 arg1 juice 1013:1017 simulated gastrointestinal digestive juice 976:1017 simulated gastrointestinal digestive juice 976:1017 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 3 65 theme g·L-1 658:662 arg1 yield 643:647 the highest triterpene yield 620:647 the highest triterpene yield of 0.527 g·L-1 620:662 Under the optimal conditions, the highest triterpene yield of 0.527 g·L-1 was obtained, which was 4.705-fold higher than before optimization. 37183920 0 66 theme Gastrointestinal 163:178 arg1 Digestion 180:188 Simulated Gastrointestinal Digestion 153:188 Simulated Gastrointestinal Digestion In Vitro 153:197 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 7 67 theme α-amylase 1468:1476 arg1 activity 1456:1463 the activity 1452:1463 the activity of α-amylase (α-AL) and α-glucosidase (α-GC) in the digestive juices 1452:1532 In terms of enzyme viability, the activity of α-amylase (α-AL) and α-glucosidase (α-GC) in the digestive juices decreased dramatically. 37183920 7 68 theme enzyme 1434:1439 arg1 viability 1441:1449 enzyme viability 1434:1449 enzyme viability 1434:1449 In terms of enzyme viability, the activity of α-amylase (α-AL) and α-glucosidase (α-GC) in the digestive juices decreased dramatically. 37183920 4 69 theme simulated 976:984 arg1 water 934:938 purified water 925:938 purified water 925:938 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 4 69 theme simulated 976:984 arg1 juice 1013:1017 simulated gastrointestinal digestive juice 976:1017 simulated gastrointestinal digestive juice 976:1017 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 7 70 theme digestive 1517:1525 arg1 juices 1527:1532 the digestive juices 1513:1532 the digestive juices 1513:1532 In terms of enzyme viability, the activity of α-amylase (α-AL) and α-glucosidase (α-GC) in the digestive juices decreased dramatically. 37183920 0 71 theme Simulated 153:161 arg1 Digestion 180:188 Simulated Gastrointestinal Digestion 153:188 Simulated Gastrointestinal Digestion In Vitro 153:197 Optimization of Triterpene Yield from Ganoderma atrum HBSD Z19 (Agaricomycetes) by Optimization of Medium Components and Evaluation of Bioactivity Under Simulated Gastrointestinal Digestion In Vitro. 37183920 1 72 theme Ganoderma 240:248 arg1 atrum 250:254 Ganoderma atrum 240:254 Ganoderma atrum 240:254 The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. 37183920 2 73 theme bean 500:503 arg1 powder 510:515 bean cake powder 500:515 bean cake powder (30.2) 500:522 The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. 37183920 2 73 theme bean 500:503 arg1 30.2 518:521 30.2 518:521 30.2 518:521 The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. 37183920 5 74 theme polysaccharides 1052:1066 arg1 content 1025:1031 The content 1021:1031 The content of triterpenes and polysaccharides 1021:1066 The content of triterpenes and polysaccharides increased, except for total phenol content. 37183920 8 75 theme power 1715:1719 arg1 use 1698:1700 the effective use 1684:1700 the effective use of fermented power from G. atrum 1684:1733 The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum. 37183920 6 76 theme ABTS+⋅ 1358:1363 arg1 activity 1377:1384 the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity 1296:1384 activity 1377:1384 In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. 37183920 4 77 theme digestive 1003:1011 arg1 water 934:938 purified water 925:938 purified water 925:938 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 4 77 theme digestive 1003:1011 arg1 juice 1013:1017 simulated gastrointestinal digestive juice 976:1017 simulated gastrointestinal digestive juice 976:1017 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 7 78 from activity 1456:1463 arg1 juices 1527:1532 the digestive juices 1513:1532 the digestive juices 1513:1532 In terms of enzyme viability, the activity of α-amylase (α-AL) and α-glucosidase (α-GC) in the digestive juices decreased dramatically. 37183920 7 79 theme viability 1441:1449 arg1 terms 1425:1429 terms 1425:1429 terms of enzyme viability 1425:1449 In terms of enzyme viability, the activity of α-amylase (α-AL) and α-glucosidase (α-GC) in the digestive juices decreased dramatically. 37183920 2 80 theme medium 453:458 arg1 g·L-1 473:477 g·L-1 473:477 g·L-1 473:477 The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. 37183920 2 80 theme medium 453:458 arg1 glucose 484:490 glucose (46.0) 484:497 glucose (46.0) 484:497 The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. 37183920 2 80 theme medium 453:458 arg1 composition 460:470 The optimal medium composition 441:470 The optimal medium composition (g·L-1) 441:478 The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. 37183920 4 81 theme digestive 959:967 arg1 juice 969:973 simulated gastric digestive juice 941:973 simulated gastric digestive juice 941:973 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 37183920 4 81 theme digestive 959:967 arg1 water 934:938 purified water 925:938 purified water 925:938 The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). 36814294 8 0 theme wild-type 1690:1698 arg1 plants 1708:1713 wild-type control plants 1690:1713 wild-type control plants 1690:1713 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 1 1 theme biomass 259:265 arg1 accumulation 267:278 their high biomass accumulation 248:278 their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 248:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 9 2 theme lignin 1722:1727 arg1 content 1729:1735 Total lignin content 1716:1735 Total lignin content of the transgenic plants was ~ 15-24% higher 1716:1780 Total lignin content of the transgenic plants was ~ 15-24% higher compared with control plants. 36814294 12 3 theme supply 2391:2396 arg1 chains 2398:2403 lignocellulosic biomass supply chains 2367:2403 lignocellulosic biomass supply chains 2367:2403 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 7 4 theme independent 1486:1496 arg1 lines 1529:1533 Four independent transgenic ZmMYB167 Miscanthus lines 1481:1533 Four independent transgenic ZmMYB167 Miscanthus lines 1481:1533 Four independent transgenic ZmMYB167 Miscanthus lines were obtained. 36814294 11 5 theme efficiency 2084:2093 arg1 yields 2095:2100 enzymatic saccharification efficiency yields 2057:2100 enzymatic saccharification efficiency yields 2057:2100 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 11 6 theme saccharification 2067:2082 arg1 yields 2095:2100 enzymatic saccharification efficiency yields 2057:2100 enzymatic saccharification efficiency yields 2057:2100 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 4 7 theme wide 893:896 arg1 range 898:902 a wide range 891:902 a wide range of locations 891:915 Certain Miscanthus sinensis genotypes are particularly interesting for their biomass productivity across a wide range of locations. 36814294 3 8 theme development 735:745 arg1 goals 747:751 sustainable development goals 723:751 sustainable development goals for a growing bio-based economy 723:783 Hence, up-scaling of Miscanthus cultivation as a source of biomass for renewable energy could play an important role to strategically address sustainable development goals for a growing bio-based economy. 36814294 6 9 theme M. 1295:1296 arg1 sinensis 1298:1305 transgenic M. sinensis 1284:1305 transgenic M. sinensis 1284:1305 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 11 10 theme enzymatic 2057:2065 arg1 yields 2095:2100 enzymatic saccharification efficiency yields 2057:2100 enzymatic saccharification efficiency yields 2057:2100 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 7 11 theme Miscanthus 1518:1527 arg1 lines 1529:1533 Four independent transgenic ZmMYB167 Miscanthus lines 1481:1533 Four independent transgenic ZmMYB167 Miscanthus lines 1481:1533 Four independent transgenic ZmMYB167 Miscanthus lines were obtained. 36814294 9 12 theme transgenic 1744:1753 arg1 plants 1755:1760 the transgenic plants 1740:1760 the transgenic plants was ~ 15-24% higher 1740:1780 Total lignin content of the transgenic plants was ~ 15-24% higher compared with control plants. 36814294 9 13 theme control 1796:1802 arg1 plants 1804:1809 control plants 1796:1809 control plants 1796:1809 Total lignin content of the transgenic plants was ~ 15-24% higher compared with control plants. 36814294 1 14 theme leading 193:199 arg1 grasses 136:142 BACKGROUND Perennial C4 grasses 112:142 BACKGROUND Perennial C4 grasses from the genus Miscanthus 112:168 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 14 theme leading 193:199 arg1 crops 235:239 leading and promising dedicated bioenergy crops 193:239 leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 193:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 15 with land 292:295 arg1 impacts 320:326 low environmental impacts 302:326 low environmental impacts 302:326 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 15 with land 292:295 arg1 requirements 344:355 maintenance requirements 332:355 maintenance requirements 332:355 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 11 16 theme energy 2195:2200 arg1 yield 2202:2206 10% higher energy yield 2184:2206 10% higher energy yield per hectare 2184:2218 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 3 17 theme growing 759:765 arg1 economy 777:783 a growing bio-based economy 757:783 a growing bio-based economy 757:783 Hence, up-scaling of Miscanthus cultivation as a source of biomass for renewable energy could play an important role to strategically address sustainable development goals for a growing bio-based economy. 36814294 1 18 theme promising 205:213 arg1 grasses 136:142 BACKGROUND Perennial C4 grasses 112:142 BACKGROUND Perennial C4 grasses from the genus Miscanthus 112:168 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 18 theme promising 205:213 arg1 crops 235:239 leading and promising dedicated bioenergy crops 193:239 leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 193:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 2 19 theme carbon 552:557 arg1 emissions 559:567 the net zero carbon emissions 539:567 re-direct the net zero carbon emissions trajectory 529:578 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 12 20 theme renewable 2435:2443 arg1 bioenergy 2445:2453 renewable bioenergy 2435:2453 renewable bioenergy 2435:2453 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 6 21 theme ZmMYB167 1381:1388 arg1 expression 1367:1376 expression 1367:1376 expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses 1367:1478 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 11 22 theme lignin 2015:2020 arg1 composition 2022:2032 lignin composition 2015:2032 lignin composition 2015:2032 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 1 23 theme bioenergy 225:233 arg1 grasses 136:142 BACKGROUND Perennial C4 grasses 112:142 BACKGROUND Perennial C4 grasses from the genus Miscanthus 112:168 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 23 theme bioenergy 225:233 arg1 crops 235:239 leading and promising dedicated bioenergy crops 193:239 leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 193:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 3 24 theme Miscanthus 602:611 arg1 cultivation 613:623 Miscanthus cultivation 602:623 Miscanthus cultivation 602:623 Hence, up-scaling of Miscanthus cultivation as a source of biomass for renewable energy could play an important role to strategically address sustainable development goals for a growing bio-based economy. 36814294 1 25 theme C4 133:134 arg1 grasses 136:142 BACKGROUND Perennial C4 grasses 112:142 BACKGROUND Perennial C4 grasses from the genus Miscanthus 112:168 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 25 theme C4 133:134 arg1 crops 235:239 leading and promising dedicated bioenergy crops 193:239 leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 193:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 11 26 theme Miscanthus 2150:2159 arg1 biomass 2161:2167 Miscanthus biomass 2150:2167 Miscanthus biomass 2150:2167 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 5 27 theme genetic 1093:1099 arg1 strategy 1133:1140 a feasible strategy 1122:1140 a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass 1122:1255 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 5 27 theme genetic 1093:1099 arg1 engineering 1101:1111 genetic engineering 1093:1111 genetic engineering 1093:1111 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 3 28 theme biomass 640:646 arg1 source 630:635 a source 628:635 a source of biomass for renewable energy 628:667 Hence, up-scaling of Miscanthus cultivation as a source of biomass for renewable energy could play an important role to strategically address sustainable development goals for a growing bio-based economy. 36814294 5 29 theme energy 977:982 arg1 density 984:990 a higher energy density 968:990 a higher energy density than cell wall polysaccharides 968:1021 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 8 30 theme Agronomic 1550:1558 arg1 tillering 1589:1597 tillering 1589:1597 tillering 1589:1597 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 8 30 theme Agronomic 1550:1558 arg1 height 1581:1586 plant height 1575:1586 plant height 1575:1586 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 8 30 theme Agronomic 1550:1558 arg1 weight 1620:1625 above-ground dry weight 1603:1625 above-ground dry weight 1603:1625 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 8 30 theme Agronomic 1550:1558 arg1 traits 1560:1565 Agronomic traits 1550:1565 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants 1550:1658 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 11 31 theme equivalent 2170:2179 arg1 levels 2140:2145 total energy levels 2127:2145 total energy levels 2127:2145 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 5 32 theme sinensis 1156:1163 arg1 biomass 1165:1171 M. sinensis biomass 1153:1171 M. sinensis biomass with increased lignin content 1153:1201 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 5 33 theme biomass 934:940 arg1 lignin 952:957 the aromatic biomass component lignin 921:957 the aromatic biomass component lignin 921:957 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 5 33 theme biomass 934:940 arg1 indicator 1051:1059 an indicator 1048:1059 an indicator for heating or calorific value 1048:1090 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 2 34 theme bioenergy 504:512 arg1 sources 514:520 alternative, affordable and green bioenergy sources 470:520 alternative, affordable and green bioenergy sources 470:520 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 12 35 theme lignocellulosic 2367:2381 arg1 chains 2398:2403 lignocellulosic biomass supply chains 2367:2403 lignocellulosic biomass supply chains 2367:2403 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 1 36 from Miscanthus 159:168 arg1 grasses 136:142 BACKGROUND Perennial C4 grasses 112:142 BACKGROUND Perennial C4 grasses from the genus Miscanthus 112:168 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 36 from Miscanthus 159:168 arg1 crops 235:239 leading and promising dedicated bioenergy crops 193:239 leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 193:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 2 37 theme net 543:545 arg1 emissions 559:567 the net zero carbon emissions 539:567 re-direct the net zero carbon emissions trajectory 529:578 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 8 38 theme plant 1575:1579 arg1 height 1581:1586 plant height 1575:1586 plant height 1575:1586 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 4 39 theme Miscanthus 794:803 arg1 genotypes 814:822 Certain Miscanthus sinensis genotypes 786:822 Certain Miscanthus sinensis genotypes 786:822 Certain Miscanthus sinensis genotypes are particularly interesting for their biomass productivity across a wide range of locations. 36814294 5 40 with biomass 1165:1171 arg1 content 1195:1201 increased lignin content 1178:1201 increased lignin content 1178:1201 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 11 41 from levels 2140:2145 arg1 biomass 2161:2167 Miscanthus biomass 2150:2167 Miscanthus biomass 2150:2167 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 2 42 theme re-direct 529:537 arg1 trajectory 569:578 re-direct the net zero carbon emissions trajectory 529:578 re-direct the net zero carbon emissions trajectory 529:578 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 6 43 theme transcription 1397:1409 arg1 factor 1411:1416 a MYB transcription factor 1391:1416 a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses 1391:1478 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 6 43 theme transcription 1397:1409 arg1 ZmMYB167 1381:1388 ZmMYB167 1381:1388 ZmMYB167 1381:1388 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 11 44 theme total 2127:2131 arg1 levels 2140:2145 total energy levels 2127:2145 total energy levels 2127:2145 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 2 45 theme urgent 395:400 arg1 need 436:439 an urgent socio-political and environmental need 392:439 an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory 392:578 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 0 46 theme Transgenic 0:9 arg1 sinensis 31:38 Transgenic ZmMYB167 Miscanthus sinensis 0:38 Transgenic ZmMYB167 Miscanthus sinensis with increased lignin to boost bioenergy generation for the bioeconomy. 0:110 Transgenic ZmMYB167 Miscanthus sinensis with increased lignin to boost bioenergy generation for the bioeconomy. 36814294 1 47 theme marginal 283:290 arg1 land 292:295 marginal land 283:295 marginal land with low environmental impacts and maintenance requirements over its productive life 283:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 8 48 theme dry 1616:1618 arg1 weight 1620:1625 above-ground dry weight 1603:1625 above-ground dry weight 1603:1625 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 12 49 theme genetic 2289:2295 arg1 interventions 2319:2331 genetic lignin bioengineering interventions 2289:2331 genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy 2289:2453 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 11 50 theme transgenic 1983:1992 arg1 plants 1994:1999 transgenic plants 1983:1999 transgenic plants 1983:1999 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 0 51 theme Miscanthus 20:29 arg1 sinensis 31:38 Transgenic ZmMYB167 Miscanthus sinensis 0:38 Transgenic ZmMYB167 Miscanthus sinensis with increased lignin to boost bioenergy generation for the bioeconomy. 0:110 Transgenic ZmMYB167 Miscanthus sinensis with increased lignin to boost bioenergy generation for the bioeconomy. 36814294 5 52 theme energetic 1226:1234 arg1 value 1236:1240 the energetic value 1222:1240 the energetic value of the biomass 1222:1255 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 5 53 theme wall 1002:1005 arg1 polysaccharides 1007:1021 cell wall polysaccharides 997:1021 cell wall polysaccharides 997:1021 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 4 54 theme biomass 863:869 arg1 productivity 871:882 their biomass productivity 857:882 their biomass productivity 857:882 Certain Miscanthus sinensis genotypes are particularly interesting for their biomass productivity across a wide range of locations. 36814294 11 55 theme ZmMYB167 1971:1978 arg1 expression 1957:1966 expression 1957:1966 expression of ZmMYB167 in transgenic plants 1957:1999 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 6 56 theme C4 1469:1470 arg1 grasses 1472:1478 C3 and C4 grasses 1462:1478 C3 and C4 grasses 1462:1478 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 1 57 theme environmental 306:318 arg1 impacts 320:326 low environmental impacts 302:326 low environmental impacts 302:326 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 5 58 theme lignin 1188:1193 arg1 content 1195:1201 increased lignin content 1178:1201 increased lignin content 1178:1201 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 3 59 theme renewable 652:660 arg1 energy 662:667 renewable energy 652:667 renewable energy 652:667 Hence, up-scaling of Miscanthus cultivation as a source of biomass for renewable energy could play an important role to strategically address sustainable development goals for a growing bio-based economy. 36814294 6 60 theme C3 1462:1463 arg1 grasses 1472:1478 C3 and C4 grasses 1462:1478 C3 and C4 grasses 1462:1478 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 5 61 theme calorific 1076:1084 arg1 value 1086:1090 calorific value 1076:1090 calorific value 1076:1090 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 8 62 theme plants 1653:1658 arg1 tillering 1589:1597 tillering 1589:1597 tillering 1589:1597 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 8 62 theme plants 1653:1658 arg1 height 1581:1586 plant height 1575:1586 plant height 1575:1586 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 8 62 theme plants 1653:1658 arg1 weight 1620:1625 above-ground dry weight 1603:1625 above-ground dry weight 1603:1625 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 1 63 theme genus 153:157 arg1 Miscanthus 159:168 the genus Miscanthus 149:168 the genus Miscanthus 149:168 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 5 64 theme increased 1178:1186 arg1 content 1195:1201 increased lignin content 1178:1201 increased lignin content 1178:1201 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 3 65 theme sustainable 723:733 arg1 goals 747:751 sustainable development goals 723:751 sustainable development goals for a growing bio-based economy 723:783 Hence, up-scaling of Miscanthus cultivation as a source of biomass for renewable energy could play an important role to strategically address sustainable development goals for a growing bio-based economy. 36814294 6 66 theme Agrobacterium-mediated 1325:1346 arg1 transformation 1348:1361 Agrobacterium-mediated transformation 1325:1361 Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses 1325:1478 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 1 67 theme high 254:257 arg1 accumulation 267:278 their high biomass accumulation 248:278 their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 248:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 4 68 theme locations 907:915 arg1 range 898:902 a wide range 891:902 a wide range of locations 891:915 Certain Miscanthus sinensis genotypes are particularly interesting for their biomass productivity across a wide range of locations. 36814294 10 69 theme structural 1825:1834 arg1 xylan 1862:1866 xylan 1862:1866 xylan 1862:1866 However, the structural carbohydrates, glucan and xylan, were decreased by ~ 2-7% and ~ 8-10%, respectively, in the transgenic plants. 36814294 10 69 theme structural 1825:1834 arg1 glucan 1851:1856 glucan 1851:1856 glucan 1851:1856 However, the structural carbohydrates, glucan and xylan, were decreased by ~ 2-7% and ~ 8-10%, respectively, in the transgenic plants. 36814294 10 69 theme structural 1825:1834 arg1 carbohydrates 1836:1848 the structural carbohydrates 1821:1848 the structural carbohydrates 1821:1848 However, the structural carbohydrates, glucan and xylan, were decreased by ~ 2-7% and ~ 8-10%, respectively, in the transgenic plants. 36814294 5 70 theme biomass 1249:1255 arg1 value 1236:1240 the energetic value 1222:1240 the energetic value of the biomass 1222:1255 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 7 71 theme transgenic 1498:1507 arg1 lines 1529:1533 Four independent transgenic ZmMYB167 Miscanthus lines 1481:1533 Four independent transgenic ZmMYB167 Miscanthus lines 1481:1533 Four independent transgenic ZmMYB167 Miscanthus lines were obtained. 36814294 8 72 theme control 1700:1706 arg1 plants 1708:1713 wild-type control plants 1690:1713 wild-type control plants 1690:1713 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 7 73 theme ZmMYB167 1509:1516 arg1 lines 1529:1533 Four independent transgenic ZmMYB167 Miscanthus lines 1481:1533 Four independent transgenic ZmMYB167 Miscanthus lines 1481:1533 Four independent transgenic ZmMYB167 Miscanthus lines were obtained. 36814294 6 74 theme transgenic 1284:1293 arg1 sinensis 1298:1305 transgenic M. sinensis 1284:1305 transgenic M. sinensis 1284:1305 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 12 75 dep CONCLUSIONS 2221:2231 arg1 highlights 2244:2253 highlights 2244:2253 highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy 2244:2453 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 9 76 theme plants 1755:1760 arg1 content 1729:1735 Total lignin content 1716:1735 Total lignin content of the transgenic plants was ~ 15-24% higher 1716:1780 Total lignin content of the transgenic plants was ~ 15-24% higher compared with control plants. 36814294 1 77 from accumulation 267:278 arg1 land 292:295 marginal land 283:295 marginal land with low environmental impacts and maintenance requirements over its productive life 283:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 11 78 theme higher 2188:2193 arg1 yield 2202:2206 10% higher energy yield 2184:2206 10% higher energy yield per hectare 2184:2218 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 2 79 theme emissions 559:567 arg1 trajectory 569:578 re-direct the net zero carbon emissions trajectory 529:578 re-direct the net zero carbon emissions trajectory 529:578 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 12 80 theme bioenergy 2445:2453 arg1 production 2421:2430 sustainable production 2409:2430 sustainable production of renewable bioenergy 2409:2453 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 3 81 theme bio-based 767:775 arg1 economy 777:783 a growing bio-based economy 757:783 a growing bio-based economy 757:783 Hence, up-scaling of Miscanthus cultivation as a source of biomass for renewable energy could play an important role to strategically address sustainable development goals for a growing bio-based economy. 36814294 3 82 theme cultivation 613:623 arg1 up-scaling 588:597 up-scaling 588:597 up-scaling of Miscanthus cultivation as a source of biomass for renewable energy 588:667 Hence, up-scaling of Miscanthus cultivation as a source of biomass for renewable energy could play an important role to strategically address sustainable development goals for a growing bio-based economy. 36814294 1 83 theme dedicated 215:223 arg1 grasses 136:142 BACKGROUND Perennial C4 grasses 112:142 BACKGROUND Perennial C4 grasses from the genus Miscanthus 112:168 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 83 theme dedicated 215:223 arg1 crops 235:239 leading and promising dedicated bioenergy crops 193:239 leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 193:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 11 84 theme energy 2133:2138 arg1 levels 2140:2145 total energy levels 2127:2145 total energy levels 2127:2145 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 5 85 theme feasible 1124:1131 arg1 strategy 1133:1140 a feasible strategy 1122:1140 a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass 1122:1255 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 5 85 theme feasible 1124:1131 arg1 engineering 1101:1111 genetic engineering 1093:1111 genetic engineering 1093:1111 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 1 86 theme Perennial 123:131 arg1 grasses 136:142 BACKGROUND Perennial C4 grasses 112:142 BACKGROUND Perennial C4 grasses from the genus Miscanthus 112:168 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 86 theme Perennial 123:131 arg1 crops 235:239 leading and promising dedicated bioenergy crops 193:239 leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 193:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 6 87 from biosynthesis 1446:1457 arg1 grasses 1472:1478 C3 and C4 grasses 1462:1478 C3 and C4 grasses 1462:1478 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 6 88 theme MYB 1393:1395 arg1 factor 1411:1416 a MYB transcription factor 1391:1416 a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses 1391:1478 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 6 88 theme MYB 1393:1395 arg1 ZmMYB167 1381:1388 ZmMYB167 1381:1388 ZmMYB167 1381:1388 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 12 89 theme sustainable 2409:2419 arg1 production 2421:2430 sustainable production 2409:2430 sustainable production of renewable bioenergy 2409:2453 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 11 90 theme phenolic 2035:2042 arg1 compounds 2044:2052 phenolic compounds 2035:2052 phenolic compounds 2035:2052 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 5 91 theme higher 970:975 arg1 density 984:990 a higher energy density 968:990 a higher energy density than cell wall polysaccharides 968:1021 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 12 92 theme bioengineering 2304:2317 arg1 interventions 2319:2331 genetic lignin bioengineering interventions 2289:2331 genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy 2289:2453 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 0 93 theme bioenergy 71:79 arg1 generation 81:90 bioenergy generation 71:90 bioenergy generation 71:90 Transgenic ZmMYB167 Miscanthus sinensis with increased lignin to boost bioenergy generation for the bioeconomy. 36814294 10 94 theme % 1892:1892 arg1 % 1904:1904 by ~ 2-7% and ~ 8-10% 1884:1904 by ~ 2-7% and ~ 8-10% 1884:1904 However, the structural carbohydrates, glucan and xylan, were decreased by ~ 2-7% and ~ 8-10%, respectively, in the transgenic plants. 36814294 5 95 theme aromatic 925:932 arg1 lignin 952:957 the aromatic biomass component lignin 921:957 the aromatic biomass component lignin 921:957 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 5 95 theme aromatic 925:932 arg1 indicator 1051:1059 an indicator 1048:1059 an indicator for heating or calorific value 1048:1090 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 2 96 theme sources 514:520 arg1 production 456:465 the production 452:465 the production of alternative, affordable and green bioenergy sources 452:520 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 12 97 theme biomass 2383:2389 arg1 chains 2398:2403 lignocellulosic biomass supply chains 2367:2403 lignocellulosic biomass supply chains 2367:2403 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 11 98 from expression 1957:1966 arg1 plants 1994:1999 transgenic plants 1983:1999 transgenic plants 1983:1999 Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. 36814294 6 99 dep RESULTS 1258:1264 arg1 generated 1312:1320 generated 1312:1320 were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses 1307:1478 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 6 100 theme lignin 1439:1444 arg1 biosynthesis 1446:1457 lignin biosynthesis 1439:1457 lignin biosynthesis in C3 and C4 grasses 1439:1478 RESULTS For this purpose, transgenic M. sinensis were generated by Agrobacterium-mediated transformation for expression of ZmMYB167, a MYB transcription factor known for regulating lignin biosynthesis in C3 and C4 grasses. 36814294 5 101 theme component 942:950 arg1 lignin 952:957 the aromatic biomass component lignin 921:957 the aromatic biomass component lignin 921:957 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 5 101 theme component 942:950 arg1 indicator 1051:1059 an indicator 1048:1059 an indicator for heating or calorific value 1048:1090 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 2 102 theme green 498:502 arg1 sources 514:520 alternative, affordable and green bioenergy sources 470:520 alternative, affordable and green bioenergy sources 470:520 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 1 103 theme productive 366:375 arg1 life 377:380 its productive life 362:380 its productive life 362:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 12 104 theme lignin 2297:2302 arg1 interventions 2319:2331 genetic lignin bioengineering interventions 2289:2331 genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy 2289:2453 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 4 105 theme Certain 786:792 arg1 genotypes 814:822 Certain Miscanthus sinensis genotypes 786:822 Certain Miscanthus sinensis genotypes 786:822 Certain Miscanthus sinensis genotypes are particularly interesting for their biomass productivity across a wide range of locations. 36814294 8 106 theme above-ground 1603:1614 arg1 weight 1620:1625 above-ground dry weight 1603:1625 above-ground dry weight 1603:1625 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 4 107 theme sinensis 805:812 arg1 genotypes 814:822 Certain Miscanthus sinensis genotypes 786:822 Certain Miscanthus sinensis genotypes 786:822 Certain Miscanthus sinensis genotypes are particularly interesting for their biomass productivity across a wide range of locations. 36814294 2 108 theme socio-political 402:416 arg1 need 436:439 an urgent socio-political and environmental need 392:439 an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory 392:578 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 0 109 theme ZmMYB167 11:18 arg1 sinensis 31:38 Transgenic ZmMYB167 Miscanthus sinensis 0:38 Transgenic ZmMYB167 Miscanthus sinensis with increased lignin to boost bioenergy generation for the bioeconomy. 0:110 Transgenic ZmMYB167 Miscanthus sinensis with increased lignin to boost bioenergy generation for the bioeconomy. 36814294 5 110 theme M. 1153:1154 arg1 biomass 1165:1171 M. sinensis biomass 1153:1171 M. sinensis biomass with increased lignin content 1153:1201 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 9 111 theme Total 1716:1720 arg1 content 1729:1735 Total lignin content 1716:1735 Total lignin content of the transgenic plants was ~ 15-24% higher 1716:1780 Total lignin content of the transgenic plants was ~ 15-24% higher compared with control plants. 36814294 9 112 theme higher 1775:1780 arg1 plants 1755:1760 the transgenic plants 1740:1760 the transgenic plants was ~ 15-24% higher 1740:1780 Total lignin content of the transgenic plants was ~ 15-24% higher compared with control plants. 36814294 12 113 theme suitable 2269:2276 arg1 ZmMYB167 2255:2262 ZmMYB167 2255:2262 ZmMYB167 2255:2262 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 12 113 theme suitable 2269:2276 arg1 target 2278:2283 a suitable target 2267:2283 a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy 2267:2453 CONCLUSIONS This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy. 36814294 5 114 theme cell 997:1000 arg1 polysaccharides 1007:1021 cell wall polysaccharides 997:1021 cell wall polysaccharides 997:1021 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 0 115 theme increased 45:53 arg1 lignin 55:60 increased lignin 45:60 increased lignin to boost bioenergy generation for the bioeconomy 45:109 Transgenic ZmMYB167 Miscanthus sinensis with increased lignin to boost bioenergy generation for the bioeconomy. 36814294 1 116 theme low 302:304 arg1 impacts 320:326 low environmental impacts 302:326 low environmental impacts 302:326 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 2 117 theme affordable 483:492 arg1 sources 514:520 alternative, affordable and green bioenergy sources 470:520 alternative, affordable and green bioenergy sources 470:520 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 8 118 theme transgenic 1642:1651 arg1 plants 1653:1658 the transgenic plants 1638:1658 the transgenic plants 1638:1658 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 0 119 with sinensis 31:38 arg1 lignin 55:60 increased lignin 45:60 increased lignin to boost bioenergy generation for the bioeconomy 45:109 Transgenic ZmMYB167 Miscanthus sinensis with increased lignin to boost bioenergy generation for the bioeconomy. 36814294 2 120 theme environmental 422:434 arg1 need 436:439 an urgent socio-political and environmental need 392:439 an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory 392:578 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 2 121 theme alternative 470:480 arg1 sources 514:520 alternative, affordable and green bioenergy sources 470:520 alternative, affordable and green bioenergy sources 470:520 There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. 36814294 5 122 dep strategy 1133:1140 arg1 develop 1145:1151 develop 1145:1151 to develop M. sinensis biomass with increased lignin content 1142:1201 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 5 122 dep strategy 1133:1140 arg1 improving 1212:1220 improving 1212:1220 thus improving the energetic value of the biomass 1207:1255 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 3 123 theme important 683:691 arg1 role 693:696 an important role 680:696 an important role 680:696 Hence, up-scaling of Miscanthus cultivation as a source of biomass for renewable energy could play an important role to strategically address sustainable development goals for a growing bio-based economy. 36814294 8 124 dep height 1581:1586 arg1 biomass 1627:1633 biomass 1627:1633 biomass 1627:1633 Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. 36814294 1 125 theme maintenance 332:342 arg1 requirements 344:355 maintenance requirements 332:355 maintenance requirements 332:355 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 126 theme BACKGROUND 112:121 arg1 grasses 136:142 BACKGROUND Perennial C4 grasses 112:142 BACKGROUND Perennial C4 grasses from the genus Miscanthus 112:168 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 126 theme BACKGROUND 112:121 arg1 crops 235:239 leading and promising dedicated bioenergy crops 193:239 leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 193:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 10 127 theme transgenic 1928:1937 arg1 plants 1939:1944 the transgenic plants 1924:1944 the transgenic plants 1924:1944 However, the structural carbohydrates, glucan and xylan, were decreased by ~ 2-7% and ~ 8-10%, respectively, in the transgenic plants. 36814294 5 128 used used 1040:1043 arg2 indicator 1051:1059 an indicator 1048:1059 an indicator for heating or calorific value 1048:1090 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 5 128 used used 1040:1043 arg2 lignin 952:957 the aromatic biomass component lignin 921:957 the aromatic biomass component lignin 921:957 As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. 36814294 1 129 theme due 241:243 arg1 grasses 136:142 BACKGROUND Perennial C4 grasses 112:142 BACKGROUND Perennial C4 grasses from the genus Miscanthus 112:168 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36814294 1 129 theme due 241:243 arg1 crops 235:239 leading and promising dedicated bioenergy crops 193:239 leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life 193:380 BACKGROUND Perennial C4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. 36532539 9 0 from research 2019:2026 arg1 mechanism 2051:2059 the cold adaptation mechanism 2031:2059 the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP 2031:2118 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 8 1 theme 4°C. 1626:1629 arg1 analysis 1658:1665 4°C. Quantitative real-time PCR analysis 1626:1665 4°C. Quantitative real-time PCR analysis 1626:1665 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 9 2 theme new 2141:2143 arg1 idea 2145:2148 a new idea 2139:2148 a new idea 2139:2148 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 4 3 dep adhesion 604:611 arg1 the 600:602 the 600:602 the 600:602 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 8 4 from half 1573:1576 arg1 stage 1614:1618 the corresponding growth stage 1589:1618 the corresponding growth stage 1589:1618 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 7 5 theme biofilm 1441:1447 arg1 composition 1449:1459 biofilm composition 1441:1459 biofilm composition formed under both temperatures 1441:1490 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 9 6 theme seafood 2161:2167 arg1 quality 2169:2175 seafood quality 2161:2175 seafood quality 2161:2175 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 8 7 theme diguanylate 1892:1902 arg1 cyclases 1904:1911 diguanylate cyclases 1892:1911 diguanylate cyclases 1892:1911 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 1 8 theme special 193:199 arg1 bacterium 210:218 a special spoilage bacterium 191:218 a special spoilage bacterium of seafood 191:229 Shewanella putrefaciens is a special spoilage bacterium of seafood during cold storage, which is easy to form biofilm and bring serious hazard to the seafood quality. 36532539 1 8 theme special 193:199 arg1 putrefaciens 175:186 putrefaciens 175:186 putrefaciens 175:186 Shewanella putrefaciens is a special spoilage bacterium of seafood during cold storage, which is easy to form biofilm and bring serious hazard to the seafood quality. 36532539 6 9 theme real-time 998:1006 arg1 PCR 1008:1010 quantitative real-time PCR 985:1010 quantitative real-time PCR 985:1010 High-performance liquid chromatographic-tandem mass spectrometric and quantitative real-time PCR were applied to study c-di-GMP level and genes encoding diguanylate cyclases in cells, respectively. 36532539 7 10 theme more 1395:1398 arg1 times 1365:1369 2.5 times 1361:1369 2.5 times 1361:1369 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 0 11 theme biofilm 113:119 arg1 formation 121:129 the adhesion and biofilm formation 96:129 formation 121:129 The enhanced expression of genes encoding diguanylate cyclases under cold stress contributes to the adhesion and biofilm formation of Shewanella putrefaciens WS13. 36532539 3 12 theme planktonic 549:558 arg1 state 560:564 bacterial planktonic state 539:564 bacterial planktonic state 539:564 As a ubiquitous second messenger in bacteria, c-di-GMP regulates the conversion between bacterial planktonic state and biofilm state. 36532539 4 13 used used 764:767 arg2 microscope 748:757 scanning electron microscope 730:757 scanning electron microscope 730:757 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 8 14 theme bacterial 1924:1932 arg1 adhesion 1934:1941 bacterial adhesion 1924:1941 bacterial adhesion 1924:1941 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 1 15 theme seafood 223:229 arg1 bacterium 210:218 a special spoilage bacterium 191:218 a special spoilage bacterium of seafood 191:229 Shewanella putrefaciens is a special spoilage bacterium of seafood during cold storage, which is easy to form biofilm and bring serious hazard to the seafood quality. 36532539 1 15 theme seafood 223:229 arg1 putrefaciens 175:186 putrefaciens 175:186 putrefaciens 175:186 Shewanella putrefaciens is a special spoilage bacterium of seafood during cold storage, which is easy to form biofilm and bring serious hazard to the seafood quality. 36532539 6 16 theme mass 962:965 arg1 spectrometric 967:979 High-performance liquid chromatographic-tandem mass spectrometric 915:979 High-performance liquid chromatographic-tandem mass spectrometric 915:979 High-performance liquid chromatographic-tandem mass spectrometric and quantitative real-time PCR were applied to study c-di-GMP level and genes encoding diguanylate cyclases in cells, respectively. 36532539 9 17 theme microbial 2201:2209 arg1 biology 2221:2227 microbial molecular biology 2201:2227 microbial molecular biology 2201:2227 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 0 18 theme putrefaciens 145:156 arg1 formation 121:129 the adhesion and biofilm formation 96:129 formation 121:129 The enhanced expression of genes encoding diguanylate cyclases under cold stress contributes to the adhesion and biofilm formation of Shewanella putrefaciens WS13. 36532539 6 19 theme liquid 932:937 arg1 spectrometric 967:979 High-performance liquid chromatographic-tandem mass spectrometric 915:979 High-performance liquid chromatographic-tandem mass spectrometric 915:979 High-performance liquid chromatographic-tandem mass spectrometric and quantitative real-time PCR were applied to study c-di-GMP level and genes encoding diguanylate cyclases in cells, respectively. 36532539 4 20 theme 30°C. 698:702 arg1 microscope 715:724 30°C. Atom force microscope 698:724 30°C. Atom force microscope 698:724 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 9 21 theme biology 2221:2227 arg1 perspective 2186:2196 the perspective 2182:2196 the perspective of microbial molecular biology 2182:2227 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 1 22 theme seafood 314:320 arg1 quality 322:328 the seafood quality 310:328 the seafood quality 310:328 Shewanella putrefaciens is a special spoilage bacterium of seafood during cold storage, which is easy to form biofilm and bring serious hazard to the seafood quality. 36532539 6 23 theme c-di-GMP 1034:1041 arg1 level 1043:1047 c-di-GMP level 1034:1047 c-di-GMP level 1034:1047 High-performance liquid chromatographic-tandem mass spectrometric and quantitative real-time PCR were applied to study c-di-GMP level and genes encoding diguanylate cyclases in cells, respectively. 36532539 5 24 theme phenol-sulfuric 886:900 arg1 method 907:912 phenol-sulfuric acid method 886:912 phenol-sulfuric acid method 886:912 Biofilm was analyzed by Fourier transform infrared spectroscopy, Bradford assay and phenol-sulfuric acid method. 36532539 8 25 theme c-di-GMP 1506:1513 arg1 level 1515:1519 c-di-GMP level 1506:1519 c-di-GMP level in S. putrefaciens WS13 under 30°C 1506:1554 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 4 26 theme electron 739:746 arg1 microscope 748:757 scanning electron microscope 730:757 scanning electron microscope 730:757 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 9 27 theme cold 2035:2038 arg1 mechanism 2051:2059 the cold adaptation mechanism 2031:2059 the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP 2031:2118 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 0 28 theme adhesion 100:107 arg1 formation 121:129 the adhesion and biofilm formation 96:129 formation 121:129 The enhanced expression of genes encoding diguanylate cyclases under cold stress contributes to the adhesion and biofilm formation of Shewanella putrefaciens WS13. 36532539 8 29 theme cold 1834:1837 arg1 stress 1839:1844 the cold stress 1830:1844 the cold stress 1830:1844 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 4 30 theme force 709:713 arg1 microscope 715:724 30°C. Atom force microscope 698:724 30°C. Atom force microscope 698:724 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 2 31 theme bacterial 366:374 arg1 adhesion 376:383 bacterial adhesion 366:383 bacterial adhesion 366:383 Life cycle of biofilm starts after bacterial adhesion, which is essential for the formation and development of biofilm. 36532539 9 32 theme specific 2064:2071 arg1 bacteria 2082:2089 specific spoilage bacteria 2064:2089 specific spoilage bacteria of seafood based on c-di-GMP 2064:2118 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 9 33 theme bacteria 2082:2089 arg1 mechanism 2051:2059 the cold adaptation mechanism 2031:2059 the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP 2031:2118 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 0 34 theme genes 27:31 arg1 expression 13:22 The enhanced expression 0:22 The enhanced expression of genes encoding diguanylate cyclases under cold stress 0:79 The enhanced expression of genes encoding diguanylate cyclases under cold stress contributes to the adhesion and biofilm formation of Shewanella putrefaciens WS13. 36532539 1 35 theme serious 292:298 arg1 hazard 300:305 serious hazard 292:305 serious hazard to the seafood quality 292:328 Shewanella putrefaciens is a special spoilage bacterium of seafood during cold storage, which is easy to form biofilm and bring serious hazard to the seafood quality. 36532539 7 36 theme extracellular 1299:1311 arg1 polysaccharides 1313:1327 extracellular polysaccharides 1299:1327 extracellular polysaccharides 1299:1327 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 2 37 theme biofilm 442:448 arg1 development 427:437 development 427:437 development 427:437 Life cycle of biofilm starts after bacterial adhesion, which is essential for the formation and development of biofilm. 36532539 2 37 theme biofilm 442:448 arg1 formation 413:421 formation 413:421 formation 413:421 Life cycle of biofilm starts after bacterial adhesion, which is essential for the formation and development of biofilm. 36532539 9 38 theme seafood 2094:2100 arg1 bacteria 2082:2089 specific spoilage bacteria 2064:2089 specific spoilage bacteria of seafood based on c-di-GMP 2064:2118 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 5 39 dep transform 834:842 arg1 infrared 844:851 infrared 844:851 transform infrared spectroscopy, Bradford assay and phenol-sulfuric acid method 834:912 Biofilm was analyzed by Fourier transform infrared spectroscopy, Bradford assay and phenol-sulfuric acid method. 36532539 3 40 theme second 467:472 arg1 conversion 520:529 the conversion 516:529 the conversion between bacterial planktonic state and biofilm state 516:582 As a ubiquitous second messenger in bacteria, c-di-GMP regulates the conversion between bacterial planktonic state and biofilm state. 36532539 3 40 theme second 467:472 arg1 messenger 474:482 a ubiquitous second messenger 454:482 a ubiquitous second messenger in bacteria 454:494 As a ubiquitous second messenger in bacteria, c-di-GMP regulates the conversion between bacterial planktonic state and biofilm state. 36532539 0 41 theme diguanylate 42:52 arg1 cyclases 54:61 diguanylate cyclases 42:61 diguanylate cyclases 42:61 The enhanced expression of genes encoding diguanylate cyclases under cold stress contributes to the adhesion and biofilm formation of Shewanella putrefaciens WS13. 36532539 8 42 theme genes 1877:1881 arg1 expression 1863:1872 the expression 1859:1872 the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation 1859:1963 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 8 43 theme Quantitative 1631:1642 arg1 analysis 1658:1665 4°C. Quantitative real-time PCR analysis 1626:1665 4°C. Quantitative real-time PCR analysis 1626:1665 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 7 44 theme 30°C. 1276:1280 arg1 biomass 1290:1296 30°C. Biofilm biomass 1276:1296 30°C. Biofilm biomass 1276:1296 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 8 45 theme that 1581:1584 arg1 half 1573:1576 half 1573:1576 half of that in the corresponding growth stage 1573:1618 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 8 46 theme PCR 1654:1656 arg1 analysis 1658:1665 4°C. Quantitative real-time PCR analysis 1626:1665 4°C. Quantitative real-time PCR analysis 1626:1665 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 6 47 theme High-performance 915:930 arg1 spectrometric 967:979 High-performance liquid chromatographic-tandem mass spectrometric 915:979 High-performance liquid chromatographic-tandem mass spectrometric 915:979 High-performance liquid chromatographic-tandem mass spectrometric and quantitative real-time PCR were applied to study c-di-GMP level and genes encoding diguanylate cyclases in cells, respectively. 36532539 8 48 theme growth 1607:1612 arg1 stage 1614:1618 the corresponding growth stage 1589:1618 the corresponding growth stage 1589:1618 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 7 49 theme swarming 1137:1144 arg1 mobility 1146:1153 the swarming mobility 1133:1153 the swarming mobility of S. putrefaciens WS13 1133:1177 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 7 49 theme swarming 1137:1144 arg1 weaker 1183:1188 weaker 1183:1188 weaker 1183:1188 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 2 50 theme Life 331:334 arg1 cycle 336:340 Life cycle 331:340 Life cycle of biofilm 331:351 Life cycle of biofilm starts after bacterial adhesion, which is essential for the formation and development of biofilm. 36532539 8 51 theme genes 1702:1706 arg1 expression 1688:1697 the expression 1684:1697 the expression of genes encoding diguanylate cyclases 1684:1736 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 4 52 theme putrefaciens 641:652 arg1 adhesion 604:611 adhesion 604:611 adhesion 604:611 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 4 52 theme putrefaciens 641:652 arg1 formation 625:633 biofilm formation 617:633 biofilm formation 617:633 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 3 53 from messenger 474:482 arg1 bacteria 487:494 bacteria 487:494 bacteria 487:494 As a ubiquitous second messenger in bacteria, c-di-GMP regulates the conversion between bacterial planktonic state and biofilm state. 36532539 3 54 theme bacterial 539:547 arg1 state 560:564 bacterial planktonic state 539:564 bacterial planktonic state 539:564 As a ubiquitous second messenger in bacteria, c-di-GMP regulates the conversion between bacterial planktonic state and biofilm state. 36532539 8 55 theme diguanylate 1717:1727 arg1 cyclases 1729:1736 diguanylate cyclases 1717:1736 diguanylate cyclases 1717:1736 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 1 56 theme spoilage 201:208 arg1 bacterium 210:218 a special spoilage bacterium 191:218 a special spoilage bacterium of seafood 191:229 Shewanella putrefaciens is a special spoilage bacterium of seafood during cold storage, which is easy to form biofilm and bring serious hazard to the seafood quality. 36532539 1 56 theme spoilage 201:208 arg1 putrefaciens 175:186 putrefaciens 175:186 putrefaciens 175:186 Shewanella putrefaciens is a special spoilage bacterium of seafood during cold storage, which is easy to form biofilm and bring serious hazard to the seafood quality. 36532539 6 57 theme quantitative 985:996 arg1 PCR 1008:1010 quantitative real-time PCR 985:1010 quantitative real-time PCR 985:1010 High-performance liquid chromatographic-tandem mass spectrometric and quantitative real-time PCR were applied to study c-di-GMP level and genes encoding diguanylate cyclases in cells, respectively. 36532539 4 58 theme biofilm 617:623 arg1 formation 625:633 biofilm formation 617:633 biofilm formation 617:633 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 8 59 theme biofilm 1947:1953 arg1 formation 1955:1963 biofilm formation 1947:1963 biofilm formation 1947:1963 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 3 60 theme biofilm 570:576 arg1 state 578:582 biofilm state 570:582 biofilm state 570:582 As a ubiquitous second messenger in bacteria, c-di-GMP regulates the conversion between bacterial planktonic state and biofilm state. 36532539 5 61 theme acid 902:905 arg1 method 907:912 phenol-sulfuric acid method 886:912 phenol-sulfuric acid method 886:912 Biofilm was analyzed by Fourier transform infrared spectroscopy, Bradford assay and phenol-sulfuric acid method. 36532539 6 62 theme chromatographic-tandem 939:960 arg1 spectrometric 967:979 High-performance liquid chromatographic-tandem mass spectrometric 915:979 High-performance liquid chromatographic-tandem mass spectrometric 915:979 High-performance liquid chromatographic-tandem mass spectrometric and quantitative real-time PCR were applied to study c-di-GMP level and genes encoding diguanylate cyclases in cells, respectively. 36532539 6 63 from cyclases 1080:1087 arg1 cells 1092:1096 cells 1092:1096 cells 1092:1096 High-performance liquid chromatographic-tandem mass spectrometric and quantitative real-time PCR were applied to study c-di-GMP level and genes encoding diguanylate cyclases in cells, respectively. 36532539 8 64 from stage 1614:1618 arg1 half 1573:1576 half 1573:1576 half of that in the corresponding growth stage 1573:1618 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 9 65 theme theoretical 1988:1998 arg1 foundation 2000:2009 a theoretical foundation 1986:2009 a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP 1986:2118 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 0 66 theme cold 69:72 arg1 stress 74:79 cold stress 69:79 cold stress 69:79 The enhanced expression of genes encoding diguanylate cyclases under cold stress contributes to the adhesion and biofilm formation of Shewanella putrefaciens WS13. 36532539 5 67 theme Bradford 867:874 arg1 assay 876:880 Bradford assay 867:880 Bradford assay 867:880 Biofilm was analyzed by Fourier transform infrared spectroscopy, Bradford assay and phenol-sulfuric acid method. 36532539 9 68 theme molecular 2211:2219 arg1 biology 2221:2227 microbial molecular biology 2201:2227 microbial molecular biology 2201:2227 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 7 69 theme adhesive 1214:1221 arg1 force 1223:1227 the adhesive force 1210:1227 the adhesive force under 4°C 1210:1237 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 7 69 theme adhesive 1214:1221 arg1 higher 1253:1258 higher 1253:1258 higher 1253:1258 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 4 70 theme scanning 730:737 arg1 microscope 748:757 scanning electron microscope 730:757 scanning electron microscope 730:757 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 2 71 dep formation 413:421 arg1 the 409:411 the 409:411 the 409:411 Life cycle of biofilm starts after bacterial adhesion, which is essential for the formation and development of biofilm. 36532539 9 72 theme adaptation 2040:2049 arg1 mechanism 2051:2059 the cold adaptation mechanism 2031:2059 the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP 2031:2118 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 0 73 theme enhanced 4:11 arg1 expression 13:22 The enhanced expression 0:22 The enhanced expression of genes encoding diguanylate cyclases under cold stress 0:79 The enhanced expression of genes encoding diguanylate cyclases under cold stress contributes to the adhesion and biofilm formation of Shewanella putrefaciens WS13. 36532539 7 74 theme extracellular 1333:1345 arg1 proteins 1347:1354 extracellular proteins 1333:1354 extracellular proteins 1333:1354 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 4 75 theme Atom 704:707 arg1 microscope 715:724 30°C. Atom force microscope 698:724 30°C. Atom force microscope 698:724 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 9 76 theme spoilage 2073:2080 arg1 bacteria 2082:2089 specific spoilage bacteria 2064:2089 specific spoilage bacteria of seafood based on c-di-GMP 2064:2118 This study provides a theoretical foundation for the research on the cold adaptation mechanism of specific spoilage bacteria of seafood based on c-di-GMP, and also provides a new idea to control seafood quality from the perspective of microbial molecular biology. 36532539 6 77 theme diguanylate 1068:1078 arg1 cyclases 1080:1087 diguanylate cyclases 1068:1087 diguanylate cyclases in cells, respectively 1068:1110 High-performance liquid chromatographic-tandem mass spectrometric and quantitative real-time PCR were applied to study c-di-GMP level and genes encoding diguanylate cyclases in cells, respectively. 36532539 4 78 theme bacterial 782:790 arg1 adhesion 792:799 the bacterial adhesion 778:799 the bacterial adhesion 778:799 In this study, the adhesion and biofilm formation of S. putrefaciens WS13 under 4°C were compared to those under 30°C. Atom force microscope and scanning electron microscope were used to study the bacterial adhesion. 36532539 7 79 theme putrefaciens 1161:1172 arg1 mobility 1146:1153 the swarming mobility 1133:1153 the swarming mobility of S. putrefaciens WS13 1133:1177 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 7 79 theme putrefaciens 1161:1172 arg1 weaker 1183:1188 weaker 1183:1188 weaker 1183:1188 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 7 80 theme Biofilm 1282:1288 arg1 biomass 1290:1296 30°C. Biofilm biomass 1276:1296 30°C. Biofilm biomass 1276:1296 Results showed that the swarming mobility of S. putrefaciens WS13 was weaker under 4°C, however, the adhesive force under 4°C was 4-5 times higher than that under 30°C. Biofilm biomass, extracellular polysaccharides and extracellular proteins were 2.5 times, 3 times, and 1.6 times more than those under 30°C, respectively, but biofilm composition formed under both temperatures were similar. 36532539 2 81 theme biofilm 345:351 arg1 cycle 336:340 Life cycle 331:340 Life cycle of biofilm 331:351 Life cycle of biofilm starts after bacterial adhesion, which is essential for the formation and development of biofilm. 36532539 8 82 theme real-time 1644:1652 arg1 analysis 1658:1665 4°C. Quantitative real-time PCR analysis 1626:1665 4°C. Quantitative real-time PCR analysis 1626:1665 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 5 83 dep Fourier 826:832 arg1 transform 834:842 transform 834:842 transform infrared spectroscopy, Bradford assay and phenol-sulfuric acid method 834:912 Biofilm was analyzed by Fourier transform infrared spectroscopy, Bradford assay and phenol-sulfuric acid method. 36532539 3 84 theme ubiquitous 456:465 arg1 conversion 520:529 the conversion 516:529 the conversion between bacterial planktonic state and biofilm state 516:582 As a ubiquitous second messenger in bacteria, c-di-GMP regulates the conversion between bacterial planktonic state and biofilm state. 36532539 3 84 theme ubiquitous 456:465 arg1 messenger 474:482 a ubiquitous second messenger 454:482 a ubiquitous second messenger in bacteria 454:494 As a ubiquitous second messenger in bacteria, c-di-GMP regulates the conversion between bacterial planktonic state and biofilm state. 36532539 1 85 theme cold 238:241 arg1 storage 243:249 cold storage 238:249 cold storage 238:249 Shewanella putrefaciens is a special spoilage bacterium of seafood during cold storage, which is easy to form biofilm and bring serious hazard to the seafood quality. 36532539 8 86 theme corresponding 1593:1605 arg1 stage 1614:1618 the corresponding growth stage 1589:1618 the corresponding growth stage 1589:1618 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36532539 8 87 from level 1515:1519 arg1 putrefaciens 1527:1538 putrefaciens 1527:1538 putrefaciens 1527:1538 c-di-GMP level in S. putrefaciens WS13 under 30°C was no more than half of that in the corresponding growth stage under 4°C. Quantitative real-time PCR analysis also showed that the expression of genes encoding diguanylate cyclases were significantly enhanced under 4°C than that under 30°C. S. putrefaciens WS13 adapted to the cold stress by enhancing the expression of genes encoding diguanylate cyclases to promote bacterial adhesion and biofilm formation. 36058798 7 0 theme Analytical 1195:1204 arg1 microscopy 1206:1215 Analytical microscopy 1195:1215 Analytical microscopy of gms1Δ 1195:1224 Analytical microscopy of gms1Δ demonstrated that the lack of cell-surface Gal did not affect cell growth or morphology during vegetative growth. 36058798 9 1 theme filamentous 1648:1658 arg1 growth 1660:1665 filamentous growth 1648:1665 filamentous growth in S. japonicus 1648:1681 Collectively, these findings show that Gal-containing oligosaccharides are required for cell wall integrity during filamentous growth in S. japonicus. 36058798 5 2 from mutant 853:858 arg1 gms1Δ 899:903 gms1Δ 899:903 gms1Δ 899:903 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 5 2 from mutant 853:858 arg1 S.j 912:914 S.j 912:914 S.j 912:914 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 2 3 theme residues 340:347 arg1 number 314:319 a large number 306:319 a large number of galactose (Gal) residues 306:347 The glycoproteins of fission yeast contain, in addition to mannose (Man), a large number of galactose (Gal) residues. 36058798 9 4 from growth 1660:1665 arg1 S. japonicus 1670:1681 S. japonicus 1670:1681 S. japonicus 1670:1681 Collectively, these findings show that Gal-containing oligosaccharides are required for cell wall integrity during filamentous growth in S. japonicus. 36058798 0 5 theme wall 81:84 arg1 integrity 86:94 cell wall integrity 76:94 cell wall integrity 76:94 Galactosylation of cell-surface glycoprotein required for hyphal growth and cell wall integrity in Schizosaccharomyces japonicus. 36058798 8 6 theme hyphal 1483:1488 arg1 differentiation 1490:1504 hyphal differentiation 1483:1504 hyphal differentiation 1483:1504 However, hyphal development was blocked in gms1Δ, even in the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus. 36058798 5 7 theme gms1+ 680:684 arg1 disruption 666:675 disruption 666:675 disruption 666:675 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 6 8 theme gms1 1023:1026 arg1 Disruption 1009:1018 Disruption 1009:1018 Disruption of gms1 (S.j) 1009:1032 Disruption of gms1 (S.j) resulted in a complete lack of Gal on the cell surface, indicating that Gms1 plays an essential role in supplying UDP-Gal from the cytoplasm to the Golgi lumen. 36058798 7 9 theme cell-surface 1256:1267 arg1 Gal 1269:1271 cell-surface Gal 1256:1271 cell-surface Gal 1256:1271 Analytical microscopy of gms1Δ demonstrated that the lack of cell-surface Gal did not affect cell growth or morphology during vegetative growth. 36058798 0 10 from growth 65:70 arg1 japonicus 119:127 Schizosaccharomyces japonicus 99:127 Schizosaccharomyces japonicus 99:127 Galactosylation of cell-surface glycoprotein required for hyphal growth and cell wall integrity in Schizosaccharomyces japonicus. 36058798 5 11 theme cell 995:998 arg1 surface 1000:1006 the cell surface 991:1006 the cell surface 991:1006 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 3 12 theme other 538:542 arg1 species 564:570 other Schizosaccharomyces species 538:570 other Schizosaccharomyces species 538:570 Previously, we reported that the cell-surface O-glycans of S. japonicus comprise mainly tri-saccharides (Gal-Man-Man) as a main component, in contrast to the tetra-saccharides observed in other Schizosaccharomyces species. 36058798 5 13 theme O-linked 944:951 arg1 oligosaccharide 953:967 O-linked oligosaccharide 944:967 O-linked oligosaccharide 944:967 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 6 14 theme essential 1120:1128 arg1 role 1130:1133 an essential role 1117:1133 an essential role 1117:1133 Disruption of gms1 (S.j) resulted in a complete lack of Gal on the cell surface, indicating that Gms1 plays an essential role in supplying UDP-Gal from the cytoplasm to the Golgi lumen. 36058798 5 15 theme gene 878:881 arg1 mutant 853:858 a deletion mutant 842:858 a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] 842:916 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 6 16 theme cell 1076:1079 arg1 surface 1081:1087 the cell surface 1072:1087 the cell surface 1072:1087 Disruption of gms1 (S.j) resulted in a complete lack of Gal on the cell surface, indicating that Gms1 plays an essential role in supplying UDP-Gal from the cytoplasm to the Golgi lumen. 36058798 3 17 theme cell-surface 383:394 arg1 O-glycans 396:404 the cell-surface O-glycans 379:404 the cell-surface O-glycans of S. japonicus 379:420 Previously, we reported that the cell-surface O-glycans of S. japonicus comprise mainly tri-saccharides (Gal-Man-Man) as a main component, in contrast to the tetra-saccharides observed in other Schizosaccharomyces species. 36058798 8 18 theme camptothecin 1444:1455 arg1 presence 1402:1409 the presence 1398:1409 the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus 1398:1530 However, hyphal development was blocked in gms1Δ, even in the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus. 36058798 7 19 theme vegetative 1321:1330 arg1 growth 1332:1337 vegetative growth 1321:1337 vegetative growth 1321:1337 Analytical microscopy of gms1Δ demonstrated that the lack of cell-surface Gal did not affect cell growth or morphology during vegetative growth. 36058798 5 20 theme deletion 844:851 arg1 mutant 853:858 a deletion mutant 842:858 a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] 842:916 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 4 21 from function 603:610 arg1 S. japonicus 644:655 S. japonicus 644:655 S. japonicus 644:655 Here we have investigated the function of cell-surface Gal residues in S. japonicus. 36058798 5 22 theme oligosaccharide 953:967 arg1 structures 969:978 the N- and O-linked oligosaccharide structures 933:978 the N- and O-linked oligosaccharide structures present on the cell surface 933:1006 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 6 23 from cytoplasm 1165:1173 arg1 UDP-Gal 1148:1154 UDP-Gal 1148:1154 UDP-Gal from the cytoplasm to the Golgi lumen 1148:1192 Disruption of gms1 (S.j) resulted in a complete lack of Gal on the cell surface, indicating that Gms1 plays an essential role in supplying UDP-Gal from the cytoplasm to the Golgi lumen. 36058798 3 24 theme S. japonicus 409:420 arg1 O-glycans 396:404 the cell-surface O-glycans 379:404 the cell-surface O-glycans of S. japonicus 379:420 Previously, we reported that the cell-surface O-glycans of S. japonicus comprise mainly tri-saccharides (Gal-Man-Man) as a main component, in contrast to the tetra-saccharides observed in other Schizosaccharomyces species. 36058798 2 25 theme large 308:312 arg1 number 314:319 a large number 306:319 a large number of galactose (Gal) residues 306:347 The glycoproteins of fission yeast contain, in addition to mannose (Man), a large number of galactose (Gal) residues. 36058798 1 26 theme hyphal 217:222 arg1 growth 224:229 hyphal growth 217:229 hyphal growth 217:229 Schizosaccharomyces japonicus is a dimorphic yeast, transiting between unicellular and hyphal growth. 36058798 0 27 theme glycoprotein 32:43 arg1 Galactosylation 0:14 Galactosylation 0:14 Galactosylation of cell-surface glycoprotein 0:43 Galactosylation of cell-surface glycoprotein required for hyphal growth and cell wall integrity in Schizosaccharomyces japonicus. 36058798 6 28 from lack 1057:1060 arg1 surface 1081:1087 the cell surface 1072:1087 the cell surface 1072:1087 Disruption of gms1 (S.j) resulted in a complete lack of Gal on the cell surface, indicating that Gms1 plays an essential role in supplying UDP-Gal from the cytoplasm to the Golgi lumen. 36058798 3 29 theme Schizosaccharomyces 544:562 arg1 species 564:570 other Schizosaccharomyces species 538:570 other Schizosaccharomyces species 538:570 Previously, we reported that the cell-surface O-glycans of S. japonicus comprise mainly tri-saccharides (Gal-Man-Man) as a main component, in contrast to the tetra-saccharides observed in other Schizosaccharomyces species. 36058798 5 30 theme homologous 867:876 arg1 gene 878:881 the homologous gene 863:881 the homologous gene 863:881 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 0 31 theme cell-surface 19:30 arg1 glycoprotein 32:43 cell-surface glycoprotein 19:43 cell-surface glycoprotein 19:43 Galactosylation of cell-surface glycoprotein required for hyphal growth and cell wall integrity in Schizosaccharomyces japonicus. 36058798 0 32 from integrity 86:94 arg1 japonicus 119:127 Schizosaccharomyces japonicus 99:127 Schizosaccharomyces japonicus 99:127 Galactosylation of cell-surface glycoprotein required for hyphal growth and cell wall integrity in Schizosaccharomyces japonicus. 36058798 9 33 theme Gal-containing 1572:1585 arg1 oligosaccharides 1587:1602 Gal-containing oligosaccharides 1572:1602 Gal-containing oligosaccharides 1572:1602 Collectively, these findings show that Gal-containing oligosaccharides are required for cell wall integrity during filamentous growth in S. japonicus. 36058798 3 34 located observed 526:533 arg1 species 564:570 other Schizosaccharomyces species 538:570 other Schizosaccharomyces species 538:570 Previously, we reported that the cell-surface O-glycans of S. japonicus comprise mainly tri-saccharides (Gal-Man-Man) as a main component, in contrast to the tetra-saccharides observed in other Schizosaccharomyces species. 36058798 3 34 located observed 526:533 arg2 tetra-saccharides 508:524 the tetra-saccharides 504:524 the tetra-saccharides observed in other Schizosaccharomyces species 504:570 Previously, we reported that the cell-surface O-glycans of S. japonicus comprise mainly tri-saccharides (Gal-Man-Man) as a main component, in contrast to the tetra-saccharides observed in other Schizosaccharomyces species. 36058798 4 35 theme residues 632:639 arg1 function 603:610 the function 599:610 the function of cell-surface Gal residues in S. japonicus 599:655 Here we have investigated the function of cell-surface Gal residues in S. japonicus. 36058798 6 36 theme Gal 1065:1067 arg1 lack 1057:1060 a complete lack 1046:1060 a complete lack of Gal on the cell surface 1046:1087 Disruption of gms1 (S.j) resulted in a complete lack of Gal on the cell surface, indicating that Gms1 plays an essential role in supplying UDP-Gal from the cytoplasm to the Golgi lumen. 36058798 6 37 theme complete 1048:1055 arg1 lack 1057:1060 a complete lack 1046:1060 a complete lack of Gal on the cell surface 1046:1087 Disruption of gms1 (S.j) resulted in a complete lack of Gal on the cell surface, indicating that Gms1 plays an essential role in supplying UDP-Gal from the cytoplasm to the Golgi lumen. 36058798 5 38 theme galactomannan 733:745 arg1 synthesis 747:755 galactomannan synthesis 733:755 galactomannan synthesis 733:755 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 8 39 theme inhibitor 1434:1442 arg1 camptothecin 1444:1455 the topoisomerase I inhibitor camptothecin 1414:1455 the topoisomerase I inhibitor camptothecin 1414:1455 However, hyphal development was blocked in gms1Δ, even in the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus. 36058798 2 40 theme yeast 261:265 arg1 glycoproteins 236:248 The glycoproteins 232:248 The glycoproteins of fission yeast 232:265 The glycoproteins of fission yeast contain, in addition to mannose (Man), a large number of galactose (Gal) residues. 36058798 8 41 theme topoisomerase 1418:1430 arg1 camptothecin 1444:1455 the topoisomerase I inhibitor camptothecin 1414:1455 the topoisomerase I inhibitor camptothecin 1414:1455 However, hyphal development was blocked in gms1Δ, even in the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus. 36058798 5 42 theme cell-surface 768:779 arg1 galactosylation 781:795 cell-surface galactosylation 768:795 cell-surface galactosylation in Schizosaccharomyces pombe 768:824 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 8 43 theme wild-type 1509:1517 arg1 S. japonicus 1519:1530 wild-type S. japonicus 1509:1530 wild-type S. japonicus 1509:1530 However, hyphal development was blocked in gms1Δ, even in the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus. 36058798 8 44 theme I 1432:1432 arg1 camptothecin 1444:1455 the topoisomerase I inhibitor camptothecin 1414:1455 the topoisomerase I inhibitor camptothecin 1414:1455 However, hyphal development was blocked in gms1Δ, even in the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus. 36058798 2 45 theme fission 253:259 arg1 yeast 261:265 fission yeast 253:265 fission yeast 253:265 The glycoproteins of fission yeast contain, in addition to mannose (Man), a large number of galactose (Gal) residues. 36058798 8 46 theme hyphal 1349:1354 arg1 development 1356:1366 hyphal development 1349:1366 hyphal development 1349:1366 However, hyphal development was blocked in gms1Δ, even in the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus. 36058798 3 47 dep tetra-saccharides 508:524 arg1 contrast 492:499 contrast 492:499 contrast 492:499 Previously, we reported that the cell-surface O-glycans of S. japonicus comprise mainly tri-saccharides (Gal-Man-Man) as a main component, in contrast to the tetra-saccharides observed in other Schizosaccharomyces species. 36058798 0 48 theme hyphal 58:63 arg1 growth 65:70 hyphal growth 58:70 hyphal growth 58:70 Galactosylation of cell-surface glycoprotein required for hyphal growth and cell wall integrity in Schizosaccharomyces japonicus. 36058798 5 49 link O-linked 944:951 arg1 oligosaccharide 953:967 O-linked oligosaccharide 944:967 O-linked oligosaccharide 944:967 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 0 50 gly glycoprotein 32:43 arg1 glycoprotein 32:43 cell-surface glycoprotein 19:43 cell-surface glycoprotein 19:43 Galactosylation of cell-surface glycoprotein required for hyphal growth and cell wall integrity in Schizosaccharomyces japonicus. 36058798 7 51 theme Gal 1269:1271 arg1 lack 1248:1251 the lack 1244:1251 the lack of cell-surface Gal 1244:1271 Analytical microscopy of gms1Δ demonstrated that the lack of cell-surface Gal did not affect cell growth or morphology during vegetative growth. 36058798 5 52 theme N- 937:938 arg1 structures 969:978 the N- and O-linked oligosaccharide structures 933:978 the N- and O-linked oligosaccharide structures present on the cell surface 933:1006 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 5 53 attach present 980:986 arg1 surface 1000:1006 the cell surface 991:1006 the cell surface 991:1006 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 5 53 attach present 980:986 arg2 structures 969:978 the N- and O-linked oligosaccharide structures 933:978 the N- and O-linked oligosaccharide structures present on the cell surface 933:1006 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 5 54 theme present 980:986 arg1 structures 969:978 the N- and O-linked oligosaccharide structures 933:978 the N- and O-linked oligosaccharide structures present on the cell surface 933:1006 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 9 55 theme cell 1621:1624 arg1 integrity 1631:1639 cell wall integrity 1621:1639 cell wall integrity 1621:1639 Collectively, these findings show that Gal-containing oligosaccharides are required for cell wall integrity during filamentous growth in S. japonicus. 36058798 2 56 theme galactose 324:332 arg1 residues 340:347 galactose (Gal) residues 324:347 galactose (Gal) residues 324:347 The glycoproteins of fission yeast contain, in addition to mannose (Man), a large number of galactose (Gal) residues. 36058798 2 57 gly glycoproteins 236:248 arg1 glycoproteins 236:248 The glycoproteins 232:248 The glycoproteins of fission yeast 232:265 The glycoproteins of fission yeast contain, in addition to mannose (Man), a large number of galactose (Gal) residues. 36058798 5 58 theme UDP-Gal 700:706 arg1 transporter 708:718 the UDP-Gal transporter 696:718 the UDP-Gal transporter required for galactomannan synthesis 696:755 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 5 59 from galactosylation 781:795 arg1 pombe 820:824 Schizosaccharomyces pombe 800:824 Schizosaccharomyces pombe 800:824 Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. 36058798 9 60 theme wall 1626:1629 arg1 integrity 1631:1639 cell wall integrity 1621:1639 cell wall integrity 1621:1639 Collectively, these findings show that Gal-containing oligosaccharides are required for cell wall integrity during filamentous growth in S. japonicus. 36058798 3 61 theme main 473:476 arg1 component 478:486 a main component 471:486 a main component 471:486 Previously, we reported that the cell-surface O-glycans of S. japonicus comprise mainly tri-saccharides (Gal-Man-Man) as a main component, in contrast to the tetra-saccharides observed in other Schizosaccharomyces species. 36058798 3 61 theme main 473:476 arg1 tri-saccharides 438:452 tri-saccharides 438:452 mainly tri-saccharides (Gal-Man-Man) 431:466 Previously, we reported that the cell-surface O-glycans of S. japonicus comprise mainly tri-saccharides (Gal-Man-Man) as a main component, in contrast to the tetra-saccharides observed in other Schizosaccharomyces species. 36058798 8 62 from gms1Δ 1383:1387 arg1 presence 1402:1409 the presence 1398:1409 the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus 1398:1530 However, hyphal development was blocked in gms1Δ, even in the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus. 36058798 0 63 theme cell 76:79 arg1 integrity 86:94 cell wall integrity 76:94 cell wall integrity 76:94 Galactosylation of cell-surface glycoprotein required for hyphal growth and cell wall integrity in Schizosaccharomyces japonicus. 36058798 6 64 theme Golgi 1182:1186 arg1 lumen 1188:1192 the Golgi lumen 1178:1192 the Golgi lumen 1178:1192 Disruption of gms1 (S.j) resulted in a complete lack of Gal on the cell surface, indicating that Gms1 plays an essential role in supplying UDP-Gal from the cytoplasm to the Golgi lumen. 36058798 7 65 theme cell 1288:1291 arg1 growth 1293:1298 cell growth 1288:1298 cell growth 1288:1298 Analytical microscopy of gms1Δ demonstrated that the lack of cell-surface Gal did not affect cell growth or morphology during vegetative growth. 36058798 1 66 theme dimorphic 165:173 arg1 japonicus 150:158 Schizosaccharomyces japonicus 130:158 Schizosaccharomyces japonicus 130:158 Schizosaccharomyces japonicus is a dimorphic yeast, transiting between unicellular and hyphal growth. 36058798 1 66 theme dimorphic 165:173 arg1 transiting 182:191 a dimorphic yeast, transiting 163:191 transiting 182:191 Schizosaccharomyces japonicus is a dimorphic yeast, transiting between unicellular and hyphal growth. 36058798 4 67 theme Gal 628:630 arg1 residues 632:639 cell-surface Gal residues 615:639 cell-surface Gal residues 615:639 Here we have investigated the function of cell-surface Gal residues in S. japonicus. 36058798 7 68 theme gms1Δ 1220:1224 arg1 microscopy 1206:1215 Analytical microscopy 1195:1215 Analytical microscopy of gms1Δ 1195:1224 Analytical microscopy of gms1Δ demonstrated that the lack of cell-surface Gal did not affect cell growth or morphology during vegetative growth. 36058798 4 69 theme cell-surface 615:626 arg1 residues 632:639 cell-surface Gal residues 615:639 cell-surface Gal residues 615:639 Here we have investigated the function of cell-surface Gal residues in S. japonicus. 36058798 1 70 theme yeast 175:179 arg1 japonicus 150:158 Schizosaccharomyces japonicus 130:158 Schizosaccharomyces japonicus 130:158 Schizosaccharomyces japonicus is a dimorphic yeast, transiting between unicellular and hyphal growth. 36058798 1 70 theme yeast 175:179 arg1 transiting 182:191 a dimorphic yeast, transiting 163:191 transiting 182:191 Schizosaccharomyces japonicus is a dimorphic yeast, transiting between unicellular and hyphal growth. 36058798 2 71 contain contain 267:273 arg2 number 314:319 a large number 306:319 a large number of galactose (Gal) residues 306:347 The glycoproteins of fission yeast contain, in addition to mannose (Man), a large number of galactose (Gal) residues. 36058798 2 71 contain contain 267:273 arg1 glycoproteins 236:248 The glycoproteins 232:248 The glycoproteins of fission yeast 232:265 The glycoproteins of fission yeast contain, in addition to mannose (Man), a large number of galactose (Gal) residues. 36044565 5 0 theme reduced 629:635 arg1 expenditure 644:654 reduced energy expenditure 629:654 reduced energy expenditure 629:654 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 4 1 theme VMH 493:495 arg1 neurons 497:503 VMH neurons 493:503 VMH neurons 493:503 Here, we report that genetic ablation of OGT in VMH neurons inhibits neuronal excitability. 36044565 5 2 theme energy 637:642 arg1 expenditure 644:654 reduced energy expenditure 629:654 reduced energy expenditure 629:654 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 5 3 theme rapid 585:589 arg1 gain 598:601 rapid weight gain 585:601 rapid weight gain 585:601 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 6 4 theme reduced 789:795 arg1 lipolysis 797:805 reduced lipolysis 789:805 reduced lipolysis 789:805 The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. 36044565 7 5 theme VMH 862:864 arg1 neurons 866:872 VMH neurons 862:872 VMH neurons 862:872 In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. 36044565 5 6 theme food 688:691 arg1 intake 693:698 food intake 688:698 food intake 688:698 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 8 7 theme adipose 1158:1164 arg1 innervation 1182:1192 white adipose tissue-specific innervation 1152:1192 white adipose tissue-specific innervation 1152:1192 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 7 8 theme sympathetic 930:940 arg1 innervation 942:952 the sympathetic innervation 926:952 the sympathetic innervation of white adipose tissues 926:977 In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. 36044565 5 9 theme weight 591:596 arg1 gain 598:601 rapid weight gain 585:601 rapid weight gain 585:601 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 8 10 theme white 1152:1156 arg1 innervation 1182:1192 white adipose tissue-specific innervation 1152:1192 white adipose tissue-specific innervation 1152:1192 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 8 11 theme set 1036:1038 arg1 point 1040:1044 a homeostatic set point 1022:1044 a homeostatic set point that controls body weight 1022:1070 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 8 11 theme set 1036:1038 arg1 OGT 1004:1006 OGT 1004:1006 OGT in the VMH 1004:1017 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 7 12 theme white 957:961 arg1 tissues 971:977 white adipose tissues 957:977 white adipose tissues 957:977 In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. 36044565 5 13 with Mice 537:540 arg1 deletion 571:578 VMH neuron-specific OGT deletion 547:578 VMH neuron-specific OGT deletion 547:578 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 4 14 from ablation 474:481 arg1 neurons 497:503 VMH neurons 493:503 VMH neurons 493:503 Here, we report that genetic ablation of OGT in VMH neurons inhibits neuronal excitability. 36044565 7 15 theme adipose 963:969 arg1 tissues 971:977 white adipose tissues 957:977 white adipose tissues 957:977 In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. 36044565 1 16 theme counterregulatory 154:170 arg1 response 172:179 counterregulatory response 154:179 counterregulatory response 154:179 The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. 36044565 3 17 theme O-GlcNAc 358:365 arg1 OGT 380:382 OGT 380:382 OGT 380:382 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 3 17 theme O-GlcNAc 358:365 arg1 transferase 367:377 O-GlcNAc transferase 358:377 O-GlcNAc transferase (OGT) 358:383 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 0 18 theme tissue 45:50 arg1 lipolysis 52:60 adipose tissue lipolysis 37:60 adipose tissue lipolysis 37:60 Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity. 36044565 5 19 theme neuron-specific 551:565 arg1 deletion 571:578 VMH neuron-specific OGT deletion 547:578 VMH neuron-specific OGT deletion 547:578 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 3 20 theme hormones 435:442 arg1 sensor 411:416 a cellular sensor 400:416 a cellular sensor of nutrients and hormones 400:442 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 0 21 theme hypothalamic 13:24 arg1 OGT 26:28 Ventromedial hypothalamic OGT 0:28 Ventromedial hypothalamic OGT 0:28 Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity. 36044565 4 22 theme genetic 466:472 arg1 ablation 474:481 genetic ablation 466:481 genetic ablation of OGT in VMH neurons 466:503 Here, we report that genetic ablation of OGT in VMH neurons inhibits neuronal excitability. 36044565 5 23 theme OGT 567:569 arg1 deletion 571:578 VMH neuron-specific OGT deletion 547:578 VMH neuron-specific OGT deletion 547:578 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 1 24 theme ventromedial 85:96 arg1 hypothalamus 98:109 The ventromedial hypothalamus 81:109 The ventromedial hypothalamus (VMH) 81:115 The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. 36044565 1 24 theme ventromedial 85:96 arg1 VMH 112:114 VMH 112:114 VMH 112:114 The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. 36044565 7 25 theme OGT 846:848 arg1 deletion 850:857 OGT deletion 846:857 OGT deletion in VMH neurons 846:872 In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. 36044565 0 26 theme Ventromedial 0:11 arg1 OGT 26:28 Ventromedial hypothalamic OGT 0:28 Ventromedial hypothalamic OGT 0:28 Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity. 36044565 8 27 theme body 1060:1063 arg1 weight 1065:1070 body weight 1060:1070 body weight 1060:1070 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 5 28 theme increased 604:612 arg1 adiposity 614:622 increased adiposity 604:622 increased adiposity 604:622 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 3 29 theme nutrients 421:429 arg1 sensor 411:416 a cellular sensor 400:416 a cellular sensor of nutrients and hormones 400:442 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 3 30 theme β-d-N-acetylglucosamine 278:300 arg1 O-GlcNAcylation 327:341 O-GlcNAcylation 327:341 O-GlcNAcylation 327:341 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 3 30 theme β-d-N-acetylglucosamine 278:300 arg1 modification 313:324 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification 269:324 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) 269:342 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 6 31 theme adipocyte 763:771 arg1 hypertrophy 773:783 adipocyte hypertrophy 763:783 adipocyte hypertrophy 763:783 The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. 36044565 6 32 theme white 810:814 arg1 tissues 824:830 white adipose tissues 810:830 white adipose tissues 810:830 The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. 36044565 6 33 theme adipose 816:822 arg1 tissues 824:830 white adipose tissues 810:830 white adipose tissues 810:830 The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. 36044565 3 34 theme cellular 402:409 arg1 sensor 411:416 a cellular sensor 400:416 a cellular sensor of nutrients and hormones 400:442 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 0 35 theme adipose 37:43 arg1 lipolysis 52:60 adipose tissue lipolysis 37:60 adipose tissue lipolysis 37:60 Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity. 36044565 3 36 theme O-linked 269:276 arg1 O-GlcNAcylation 327:341 O-GlcNAcylation 327:341 O-GlcNAcylation 327:341 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 3 36 theme O-linked 269:276 arg1 modification 313:324 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification 269:324 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) 269:342 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 8 37 theme tissue-specific 1166:1180 arg1 innervation 1182:1192 white adipose tissue-specific innervation 1152:1192 white adipose tissue-specific innervation 1152:1192 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 2 38 theme lipid 216:220 arg1 metabolism 222:231 lipid metabolism 216:231 lipid metabolism 216:231 However, how VMH neurons regulate lipid metabolism and energy balance remains unknown. 36044565 8 39 from OGT 1004:1006 arg1 VMH 1015:1017 the VMH 1011:1017 the VMH 1011:1017 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 5 40 theme physical 703:710 arg1 activity 712:719 physical activity 703:719 physical activity 703:719 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 5 41 theme significant 665:675 arg1 changes 677:683 significant changes 665:683 significant changes in food intake or physical activity 665:719 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 8 42 theme homeostatic 1024:1034 arg1 point 1040:1044 a homeostatic set point 1022:1044 a homeostatic set point that controls body weight 1022:1070 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 8 42 theme homeostatic 1024:1034 arg1 OGT 1004:1006 OGT 1004:1006 OGT in the VMH 1004:1017 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 4 43 theme neuronal 514:521 arg1 excitability 523:534 neuronal excitability 514:534 neuronal excitability 514:534 Here, we report that genetic ablation of OGT in VMH neurons inhibits neuronal excitability. 36044565 3 44 theme O-GlcNAc 303:310 arg1 O-GlcNAcylation 327:341 O-GlcNAcylation 327:341 O-GlcNAcylation 327:341 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 3 44 theme O-GlcNAc 303:310 arg1 modification 313:324 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification 269:324 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) 269:342 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 2 45 theme VMH 195:197 arg1 neurons 199:205 VMH neurons 195:205 VMH neurons 195:205 However, how VMH neurons regulate lipid metabolism and energy balance remains unknown. 36044565 5 46 theme VMH 547:549 arg1 deletion 571:578 VMH neuron-specific OGT deletion 547:578 VMH neuron-specific OGT deletion 547:578 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 5 47 from changes 677:683 arg1 intake 693:698 food intake 688:698 food intake 688:698 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 5 47 from changes 677:683 arg1 activity 712:719 physical activity 703:719 physical activity 703:719 Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. 36044565 8 48 theme VMH 1109:1111 arg1 importance 1091:1100 the importance 1087:1100 the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation 1087:1192 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 6 49 theme obesity 726:732 arg1 phenotype 734:742 The obesity phenotype 722:742 The obesity phenotype 722:742 The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. 36044565 1 50 theme body 138:141 arg1 weight 143:148 body weight 138:148 body weight 138:148 The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. 36044565 7 51 theme sympathetic 893:903 arg1 activity 905:912 the sympathetic activity 889:912 the sympathetic activity 889:912 In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. 36044565 8 52 theme lipid 1127:1131 arg1 metabolism 1133:1142 lipid metabolism 1127:1142 lipid metabolism 1127:1142 These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. 36044565 6 53 theme tissues 824:830 arg1 hypertrophy 773:783 adipocyte hypertrophy 763:783 adipocyte hypertrophy 763:783 The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. 36044565 6 53 theme tissues 824:830 arg1 lipolysis 797:805 reduced lipolysis 789:805 reduced lipolysis 789:805 The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. 36044565 7 54 from deletion 850:857 arg1 neurons 866:872 VMH neurons 862:872 VMH neurons 862:872 In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. 36044565 7 55 theme tissues 971:977 arg1 innervation 942:952 the sympathetic innervation 926:952 the sympathetic innervation of white adipose tissues 926:977 In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. 36044565 4 56 theme OGT 486:488 arg1 ablation 474:481 genetic ablation 466:481 genetic ablation of OGT in VMH neurons 466:503 Here, we report that genetic ablation of OGT in VMH neurons inhibits neuronal excitability. 36044565 2 57 theme energy 237:242 arg1 balance 244:250 energy balance 237:250 energy balance 237:250 However, how VMH neurons regulate lipid metabolism and energy balance remains unknown. 36044565 3 58 link O-linked 269:276 arg1 O-GlcNAcylation 327:341 O-GlcNAcylation 327:341 O-GlcNAcylation 327:341 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 36044565 3 58 link O-linked 269:276 arg1 modification 313:324 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification 269:324 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) 269:342 O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. 35562392 6 0 theme molecular 882:890 arg1 mass 892:895 the deduced molecular mass 870:895 the deduced molecular mass of pmTSP-II (110 kDa) 870:917 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 7 1 theme subsequent 1084:1093 arg1 bands 1111:1115 the subsequent smaller protein bands 1080:1115 the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners 1080:1175 This was confirmed by chitinase digestion on pmTSP-II protein leading to the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners. 35562392 1 2 link O-linked 243:250 arg1 sites 266:270 the O-linked glycosylation sites 239:270 the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II) 239:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 2 link O-linked 243:250 arg1 thrombospondin 282:295 shrimp thrombospondin 275:295 shrimp thrombospondin (pmTSP-II) 275:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 4 3 theme linear 541:546 arg1 chito-triose 548:559 linear chito-triose 541:559 linear chito-triose 541:559 The antibody well reacted with linear chito-triose, -tetraose and -pentaose conjugated with phosphatidylethanolamine lipid. 35562392 6 4 theme deduced 874:880 arg1 mass 892:895 the deduced molecular mass 870:895 the deduced molecular mass of pmTSP-II (110 kDa) 870:917 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 7 5 theme smaller 1095:1101 arg1 bands 1111:1115 the subsequent smaller protein bands 1080:1115 the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners 1080:1175 This was confirmed by chitinase digestion on pmTSP-II protein leading to the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners. 35562392 7 6 theme pmTSP-II 1052:1059 arg1 protein 1061:1067 pmTSP-II protein 1052:1067 pmTSP-II protein leading to the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners 1052:1175 This was confirmed by chitinase digestion on pmTSP-II protein leading to the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners. 35562392 6 7 theme pmTSP-II 957:964 arg1 association 942:952 additional association 931:952 additional association of pmTSP-II apart from its known disulfide bridging 931:1004 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 7 8 from 110-170 kDa 1120:1130 arg1 time- 1135:1139 time- 1135:1139 time- 1135:1139 This was confirmed by chitinase digestion on pmTSP-II protein leading to the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners. 35562392 7 8 from 110-170 kDa 1120:1130 arg1 manners 1169:1175 concentration-dependent manners 1145:1175 concentration-dependent manners 1145:1175 This was confirmed by chitinase digestion on pmTSP-II protein leading to the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners. 35562392 7 8 from 110-170 kDa 1120:1130 arg1 bands 1111:1115 the subsequent smaller protein bands 1080:1115 the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners 1080:1175 This was confirmed by chitinase digestion on pmTSP-II protein leading to the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners. 35562392 3 9 theme β1,4GNP 501:507 arg1 existence 469:477 the existence 465:477 the existence of linear and complex β1,4GNP 465:507 Antibody against O-β-GlcNAc (CTD110.6) was used to prove the existence of linear and complex β1,4GNP. 35562392 9 10 theme matrix 1431:1436 arg1 architecture 1397:1408 structural architecture 1386:1408 structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology 1386:1490 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 9 11 theme inter-chain 1351:1361 arg1 association 1363:1373 an inter-chain association 1348:1373 an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology 1348:1490 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 9 12 theme pmTSP-II 1459:1466 arg1 function 1447:1454 a novel function 1439:1454 a novel function of pmTSP-II in reproductive biology 1439:1490 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 9 12 theme pmTSP-II 1459:1466 arg1 matrix 1431:1436 egg extracellular matrix 1413:1436 egg extracellular matrix 1413:1436 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 8 13 theme chitinase 1258:1266 arg1 hydrolysis 1268:1277 extensive chitinase hydrolysis 1248:1277 extensive chitinase hydrolysis 1248:1277 These bands well reacted with CTD110.6 antibody and disappeared after extensive chitinase hydrolysis. 35562392 0 14 theme chain 101:105 arg1 association 107:117 TSP chain association 97:117 TSP chain association in egg extracellular matrix 97:145 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 0 15 from presence 29:36 arg1 association 107:117 TSP chain association 97:117 TSP chain association in egg extracellular matrix 97:145 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 9 16 from function 1336:1343 arg1 association 1363:1373 an inter-chain association 1348:1373 an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology 1348:1490 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 8 17 theme extensive 1248:1256 arg1 hydrolysis 1268:1277 extensive chitinase hydrolysis 1248:1277 extensive chitinase hydrolysis 1248:1277 These bands well reacted with CTD110.6 antibody and disappeared after extensive chitinase hydrolysis. 35562392 2 18 theme epithelial 358:367 arg1 pmTSP-II 398:405 pmTSP-II 398:405 pmTSP-II 398:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 2 18 theme epithelial 358:367 arg1 domain 388:393 the epithelial growth factor-like domain 354:393 the epithelial growth factor-like domain of pmTSP-II 354:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 0 19 theme TSP 97:99 arg1 association 107:117 TSP chain association 97:117 TSP chain association in egg extracellular matrix 97:145 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 9 20 theme extracellular 1417:1429 arg1 function 1447:1454 a novel function 1439:1454 a novel function of pmTSP-II in reproductive biology 1439:1490 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 9 20 theme extracellular 1417:1429 arg1 matrix 1431:1436 egg extracellular matrix 1413:1436 egg extracellular matrix 1413:1436 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 9 21 theme egg 1413:1415 arg1 function 1447:1454 a novel function 1439:1454 a novel function of pmTSP-II in reproductive biology 1439:1490 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 9 21 theme egg 1413:1415 arg1 matrix 1431:1436 egg extracellular matrix 1413:1436 egg extracellular matrix 1413:1436 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 3 22 theme complex 493:499 arg1 β1,4GNP 501:507 linear and complex β1,4GNP 482:507 linear and complex β1,4GNP 482:507 Antibody against O-β-GlcNAc (CTD110.6) was used to prove the existence of linear and complex β1,4GNP. 35562392 6 23 theme pmTSP-II 900:907 arg1 mass 892:895 the deduced molecular mass 870:895 the deduced molecular mass of pmTSP-II (110 kDa) 870:917 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 6 24 theme SDS-PAGE 769:776 arg1 buffer 778:783 SDS-PAGE buffer 769:783 SDS-PAGE buffer 769:783 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 0 25 theme Shrimp 0:5 arg1 TSP 23:25 TSP 23:25 TSP 23:25 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 0 25 theme Shrimp 0:5 arg1 thrombospondin 7:20 Shrimp thrombospondin 0:20 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 0:146 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 6 26 theme additional 931:940 arg1 association 942:952 additional association 931:952 additional association of pmTSP-II apart from its known disulfide bridging 931:1004 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 6 27 theme pmTSP-II 798:805 arg1 250 kDa 825:831 250 kDa 825:831 250 kDa 825:831 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 6 27 theme pmTSP-II 798:805 arg1 size 790:793 the size 786:793 the size of pmTSP-II 786:805 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 0 28 attach presence 29:36 arg1 association 107:117 TSP chain association 97:117 TSP chain association in egg extracellular matrix 97:145 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 0 28 attach presence 29:36 arg2 polymers 68:75 O-β1,4 N-acetylglucosamine polymers 41:75 O-β1,4 N-acetylglucosamine polymers 41:75 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 1 29 theme O-β 182:184 arg1 β1,4GNP 208:214 β1,4GNP 208:214 β1,4GNP 208:214 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 29 theme O-β 182:184 arg1 polymers 198:205 O-β(1,4)-GlcNAc polymers 182:205 O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II) 182:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 30 theme O-linked 243:250 arg1 sites 266:270 the O-linked glycosylation sites 239:270 the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II) 239:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 30 theme O-linked 243:250 arg1 thrombospondin 282:295 shrimp thrombospondin 275:295 shrimp thrombospondin (pmTSP-II) 275:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 5 31 theme complex 685:691 arg1 β1,4GNP 693:699 a complex β1,4GNP 683:699 a complex β1,4GNP within pmTSP-II (at MW > 250 kDa) 683:733 The immunoreactivity could also be detected with a complex β1,4GNP within pmTSP-II (at MW > 250 kDa). 35562392 2 32 theme growth 369:374 arg1 pmTSP-II 398:405 pmTSP-II 398:405 pmTSP-II 398:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 2 32 theme growth 369:374 arg1 domain 388:393 the epithelial growth factor-like domain 354:393 the epithelial growth factor-like domain of pmTSP-II 354:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 2 33 theme pmTSP-II 398:405 arg1 pmTSP-II 398:405 pmTSP-II 398:405 pmTSP-II 398:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 2 33 theme pmTSP-II 398:405 arg1 domain 388:393 the epithelial growth factor-like domain 354:393 the epithelial growth factor-like domain of pmTSP-II 354:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 1 34 theme glycosylation 252:264 arg1 sites 266:270 the O-linked glycosylation sites 239:270 the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II) 239:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 34 theme glycosylation 252:264 arg1 thrombospondin 282:295 shrimp thrombospondin 275:295 shrimp thrombospondin (pmTSP-II) 275:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 5 35 from MW > 250 kDa 721:732 arg1 pmTSP-II 708:715 pmTSP-II 708:715 pmTSP-II (at MW > 250 kDa) 708:733 The immunoreactivity could also be detected with a complex β1,4GNP within pmTSP-II (at MW > 250 kDa). 35562392 1 36 theme 1,4 186:188 arg1 β1,4GNP 208:214 β1,4GNP 208:214 β1,4GNP 208:214 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 36 theme 1,4 186:188 arg1 polymers 198:205 O-β(1,4)-GlcNAc polymers 182:205 O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II) 182:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 0 37 theme extracellular 126:138 arg1 matrix 140:145 egg extracellular matrix 122:145 egg extracellular matrix 122:145 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 7 38 theme concentration-dependent 1145:1167 arg1 manners 1169:1175 concentration-dependent manners 1145:1175 concentration-dependent manners 1145:1175 This was confirmed by chitinase digestion on pmTSP-II protein leading to the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners. 35562392 3 39 used used 451:454 arg2 Antibody 408:415 Antibody 408:415 Antibody against O-β-GlcNAc (CTD110.6) 408:445 Antibody against O-β-GlcNAc (CTD110.6) was used to prove the existence of linear and complex β1,4GNP. 35562392 6 40 dep 2.5 848:850 arg1 folds 852:856 folds 852:856 folds larger than the deduced molecular mass of pmTSP-II (110 kDa) 852:917 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 2 41 theme factor-like 376:386 arg1 pmTSP-II 398:405 pmTSP-II 398:405 pmTSP-II 398:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 2 41 theme factor-like 376:386 arg1 domain 388:393 the epithelial growth factor-like domain 354:393 the epithelial growth factor-like domain of pmTSP-II 354:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 6 42 with protein 756:762 arg1 buffer 778:783 SDS-PAGE buffer 769:783 SDS-PAGE buffer 769:783 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 0 43 theme egg 122:124 arg1 matrix 140:145 egg extracellular matrix 122:145 egg extracellular matrix 122:145 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 1 44 theme -GlcNAc 190:196 arg1 β1,4GNP 208:214 β1,4GNP 208:214 β1,4GNP 208:214 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 44 theme -GlcNAc 190:196 arg1 polymers 198:205 O-β(1,4)-GlcNAc polymers 182:205 O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II) 182:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 7 45 theme protein 1103:1109 arg1 bands 1111:1115 the subsequent smaller protein bands 1080:1115 the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners 1080:1175 This was confirmed by chitinase digestion on pmTSP-II protein leading to the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners. 35562392 1 46 theme shrimp 275:280 arg1 pmTSP-II 298:305 pmTSP-II 298:305 pmTSP-II 298:305 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 46 theme shrimp 275:280 arg1 thrombospondin 282:295 shrimp thrombospondin 275:295 shrimp thrombospondin (pmTSP-II) 275:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 9 47 theme reproductive 1471:1482 arg1 biology 1484:1490 reproductive biology 1471:1490 reproductive biology 1471:1490 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 2 48 from linkages 342:349 arg1 pmTSP-II 398:405 pmTSP-II 398:405 pmTSP-II 398:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 2 48 from linkages 342:349 arg1 domain 388:393 the epithelial growth factor-like domain 354:393 the epithelial growth factor-like domain of pmTSP-II 354:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 1 49 theme thrombospondin 282:295 arg1 sites 266:270 the O-linked glycosylation sites 239:270 the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II) 239:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 49 theme thrombospondin 282:295 arg1 thrombospondin 282:295 shrimp thrombospondin 275:295 shrimp thrombospondin (pmTSP-II) 275:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 7 50 theme chitinase 1029:1037 arg1 digestion 1039:1047 chitinase digestion 1029:1047 chitinase digestion 1029:1047 This was confirmed by chitinase digestion on pmTSP-II protein leading to the subsequent smaller protein bands at 110-170 kDa in time- and concentration-dependent manners. 35562392 1 51 gly glycosylation 252:264 arg1 thrombospondin 282:295 shrimp thrombospondin 275:295 shrimp thrombospondin (pmTSP-II) 275:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 51 gly glycosylation 252:264 arg1 pmTSP-II 298:305 pmTSP-II 298:305 pmTSP-II 298:305 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 51 gly glycosylation 252:264 arg2 thrombospondin 282:295 shrimp thrombospondin 275:295 shrimp thrombospondin (pmTSP-II) 275:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 51 gly glycosylation 252:264 arg2 sites 266:270 the O-linked glycosylation sites 239:270 the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II) 239:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 1 52 theme polymers 198:205 arg1 existence 169:177 the existence 165:177 the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II) 165:306 We characterized the existence of O-β(1,4)-GlcNAc polymers (β1,4GNP) that were anchored on the O-linked glycosylation sites of shrimp thrombospondin (pmTSP-II). 35562392 9 53 theme structural 1386:1395 arg1 architecture 1397:1408 structural architecture 1386:1408 structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology 1386:1490 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 9 54 from function 1447:1454 arg1 biology 1484:1490 reproductive biology 1471:1490 reproductive biology 1471:1490 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 3 55 theme linear 482:487 arg1 β1,4GNP 501:507 linear and complex β1,4GNP 482:507 linear and complex β1,4GNP 482:507 Antibody against O-β-GlcNAc (CTD110.6) was used to prove the existence of linear and complex β1,4GNP. 35562392 6 56 theme known 981:985 arg1 disulfide 987:995 its known disulfide 977:995 its known disulfide bridging 977:1004 Upon denaturing the protein with SDS-PAGE buffer, the size of pmTSP-II was shifted to be 250 kDa, approximately 2.5 folds larger than the deduced molecular mass of pmTSP-II (110 kDa), suggesting additional association of pmTSP-II apart from its known disulfide bridging. 35562392 0 57 theme polymers 68:75 arg1 presence 29:36 presence 29:36 presence of O-β1,4 N-acetylglucosamine polymers 29:75 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 0 57 theme polymers 68:75 arg1 function 85:92 its function 81:92 its function in TSP chain association in egg extracellular matrix 81:145 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 0 58 from function 85:92 arg1 association 107:117 TSP chain association 97:117 TSP chain association in egg extracellular matrix 97:145 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 0 59 dep thrombospondin 7:20 arg1 presence 29:36 presence 29:36 presence of O-β1,4 N-acetylglucosamine polymers 29:75 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 0 59 dep thrombospondin 7:20 arg1 function 85:92 its function 81:92 its function in TSP chain association in egg extracellular matrix 81:145 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 4 60 theme phosphatidylethanolamine 602:625 arg1 lipid 627:631 phosphatidylethanolamine lipid 602:631 phosphatidylethanolamine lipid 602:631 The antibody well reacted with linear chito-triose, -tetraose and -pentaose conjugated with phosphatidylethanolamine lipid. 35562392 2 61 theme β1,4GNP 334:340 arg1 linkages 342:349 five putative β1,4GNP linkages 320:349 five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II 320:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 9 62 theme novel 1441:1445 arg1 function 1447:1454 a novel function 1439:1454 a novel function of pmTSP-II in reproductive biology 1439:1490 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 9 62 theme novel 1441:1445 arg1 matrix 1431:1436 egg extracellular matrix 1413:1436 egg extracellular matrix 1413:1436 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 0 63 theme O-β1,4 N-acetylglucosamine 41:66 arg1 polymers 68:75 O-β1,4 N-acetylglucosamine polymers 41:75 O-β1,4 N-acetylglucosamine polymers 41:75 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 35562392 9 64 from β1,4GNP 1306:1312 arg1 pmTSP-II 1317:1324 pmTSP-II 1317:1324 pmTSP-II 1317:1324 Together, we believe that β1,4GNP on pmTSP-II serve the function in an inter-chain association to provide structural architecture of egg extracellular matrix, a novel function of pmTSP-II in reproductive biology. 35562392 2 65 theme putative 325:332 arg1 linkages 342:349 five putative β1,4GNP linkages 320:349 five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II 320:405 There were five putative β1,4GNP linkages on the epithelial growth factor-like domain of pmTSP-II. 35562392 0 66 from association 107:117 arg1 matrix 140:145 egg extracellular matrix 122:145 egg extracellular matrix 122:145 Shrimp thrombospondin (TSP): presence of O-β1,4 N-acetylglucosamine polymers and its function in TSP chain association in egg extracellular matrix. 37297422 0 0 theme Extract 74:80 arg1 Mechanism 24:32 Mechanism 24:32 Mechanism 24:32 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 0 0 theme Extract 74:80 arg1 Function 11:18 Protection Function 0:18 Protection Function 0:18 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 4 1 theme thermal 1071:1077 arg1 oxidation 1079:1087 thermal oxidation 1071:1087 thermal oxidation 1071:1087 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 2 2 dep indices 619:625 arg1 content 663:669 tocopherol content 652:669 tocopherol content 652:669 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 2 dep indices 619:625 arg1 indices 619:625 the physicochemical indices 599:625 the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity) 599:732 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 2 dep indices 619:625 arg1 content 687:693 total phenolic content 672:693 total phenolic content 672:693 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 2 dep indices 619:625 arg1 capacity 724:731 free radical scavenging capacity 700:731 free radical scavenging capacity 700:731 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 2 dep indices 619:625 arg1 composition 639:649 fatty acid composition 628:649 fatty acid composition 628:649 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 1 3 theme efficient 205:213 arg1 antioxidants 223:234 the most efficient natural antioxidants 196:234 the most efficient natural antioxidants 196:234 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 0 4 from Function 11:18 arg1 Stability 107:115 the Thermal Oxidative Stability 85:115 the Thermal Oxidative Stability of Vegetable Oils 85:133 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 5 5 theme antioxidants 1375:1386 arg1 efficiency 1361:1370 the efficiency 1357:1370 the efficiency of antioxidants 1357:1386 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 1 6 theme Rosmarinus 146:155 arg1 Rosemary 136:143 Rosemary 136:143 Rosemary (Rosmarinus officinalis L.) extract (RE) 136:184 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 1 6 theme Rosmarinus 146:155 arg1 L. 169:170 Rosmarinus officinalis L. 146:170 Rosmarinus officinalis L. 146:170 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 4 7 theme free 989:992 arg1 capacity 1013:1020 the free radical scavenging capacity 985:1020 the free radical scavenging capacity 985:1020 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 7 theme free 989:992 arg1 Ea 1064:1065 Ea 1064:1065 Ea 1064:1065 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 1 8 theme natural 215:221 arg1 antioxidants 223:234 the most efficient natural antioxidants 196:234 the most efficient natural antioxidants 196:234 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 5 9 theme positive 1288:1295 arg1 correlation 1297:1307 a significant positive correlation 1274:1307 a significant positive correlation 1274:1307 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 5 9 theme positive 1288:1295 arg1 combination 1314:1324 the combination 1310:1324 the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation 1310:1461 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 2 10 theme rapeseed 522:529 arg1 oil 531:533 rapeseed oil 522:533 rapeseed oil 522:533 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 10 theme rapeseed 522:529 arg1 oils 503:506 vegetable oils 493:506 vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 493:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 1 11 theme antioxidants 223:234 arg1 one 189:191 one 189:191 one 189:191 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 1 11 theme antioxidants 223:234 arg1 antioxidants 223:234 the most efficient natural antioxidants 196:234 the most efficient natural antioxidants 196:234 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 2 12 from capacity 351:358 arg1 stability 405:413 the thermal oxidative stability 383:413 the thermal oxidative stability of different vegetable oils 383:441 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 13 theme phenolic 678:685 arg1 indices 619:625 the physicochemical indices 599:625 the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity) 599:732 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 13 theme phenolic 678:685 arg1 content 687:693 total phenolic content 672:693 total phenolic content 672:693 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 5 14 theme inhibition 1406:1415 arg1 mechanism 1417:1425 the inhibition mechanism 1402:1425 the inhibition mechanism of RE 1402:1431 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 2 15 theme oxidative 765:773 arg1 parameters 783:792 thermal oxidative kinetic parameters 757:792 thermal oxidative kinetic parameters 757:792 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 0 16 theme Oxidative 97:105 arg1 Stability 107:115 the Thermal Oxidative Stability 85:115 the Thermal Oxidative Stability of Vegetable Oils 85:133 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 2 17 theme rice 552:555 arg1 oil 562:564 rice bran oil 552:564 rice bran oil 552:564 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 17 theme rice 552:555 arg1 oils 503:506 vegetable oils 493:506 vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 493:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 18 theme bran 557:560 arg1 oil 562:564 rice bran oil 552:564 rice bran oil 552:564 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 18 theme bran 557:560 arg1 oils 503:506 vegetable oils 493:506 vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 493:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 4 19 theme activation 1045:1054 arg1 energy 1056:1061 activation energy 1045:1061 activation energy 1045:1061 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 1 20 theme officinalis 157:167 arg1 Rosemary 136:143 Rosemary 136:143 Rosemary (Rosmarinus officinalis L.) extract (RE) 136:184 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 1 20 theme officinalis 157:167 arg1 L. 169:170 Rosmarinus officinalis L. 146:170 Rosmarinus officinalis L. 146:170 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 0 21 theme Thermal 89:95 arg1 Stability 107:115 the Thermal Oxidative Stability 85:115 the Thermal Oxidative Stability of Vegetable Oils 85:133 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 4 22 theme reaction 1123:1130 arg1 rate 1132:1135 the thermal oxidation reaction rate 1101:1135 the thermal oxidation reaction rate (k) 1101:1139 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 22 theme reaction 1123:1130 arg1 oil 1185:1187 rice bran oil 1175:1187 rice bran oil 1175:1187 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 22 theme reaction 1123:1130 arg1 k 1138:1138 k 1138:1138 k 1138:1138 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 23 theme artificial 933:942 arg1 antioxidants 944:955 artificial antioxidants 933:955 artificial antioxidants 933:955 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 2 24 theme tocopherol 652:661 arg1 content 663:669 tocopherol content 652:669 tocopherol content 652:669 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 24 theme tocopherol 652:661 arg1 indices 619:625 the physicochemical indices 599:625 the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity) 599:732 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 4 25 theme oxidation 1079:1087 arg1 energy 1056:1061 activation energy 1045:1061 activation energy 1045:1061 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 25 theme oxidation 1079:1087 arg1 capacity 1013:1020 the free radical scavenging capacity 985:1020 the free radical scavenging capacity 985:1020 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 25 theme oxidation 1079:1087 arg1 period 1033:1038 induction period 1023:1038 induction period 1023:1038 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 25 theme oxidation 1079:1087 arg1 Ea 1064:1065 Ea 1064:1065 Ea 1064:1065 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 2 26 theme different 418:426 arg1 oils 438:441 different vegetable oils 418:441 different vegetable oils 418:441 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 3 27 theme antioxidant 825:835 arg1 capacity 837:844 antioxidant capacity 825:844 antioxidant capacity 825:844 The relationships between the antioxidant capacity and thermal stability parameters were determined. 37297422 2 28 theme carnosic 461:468 arg1 acid 470:473 70% carnosic acid 457:473 70% carnosic acid 457:473 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 28 theme carnosic 461:468 arg1 RE 453:454 RE 453:454 RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 453:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 4 29 theme oxidation 1113:1121 arg1 rate 1132:1135 the thermal oxidation reaction rate 1101:1135 the thermal oxidation reaction rate (k) 1101:1139 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 29 theme oxidation 1113:1121 arg1 oil 1185:1187 rice bran oil 1175:1187 rice bran oil 1175:1187 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 29 theme oxidation 1113:1121 arg1 k 1138:1138 k 1138:1138 k 1138:1138 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 5 30 theme induction 1238:1246 arg1 IP 1256:1257 IP 1256:1257 IP 1256:1257 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 5 30 theme induction 1238:1246 arg1 period 1248:1253 the induction period 1234:1253 the induction period (IP) 1234:1258 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 0 31 theme Protection 0:9 arg1 Function 11:18 Protection Function 0:18 Protection Function 0:18 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 2 32 theme cottonseed 536:545 arg1 oil 547:549 cottonseed oil 536:549 cottonseed oil 536:549 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 32 theme cottonseed 536:545 arg1 oils 503:506 vegetable oils 493:506 vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 493:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 5 33 theme significant 1276:1286 arg1 correlation 1297:1307 a significant positive correlation 1274:1307 a significant positive correlation 1274:1307 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 5 33 theme significant 1276:1286 arg1 combination 1314:1324 the combination 1310:1324 the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation 1310:1461 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 2 34 theme vegetable 493:501 arg1 oil 531:533 rapeseed oil 522:533 rapeseed oil 522:533 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 34 theme vegetable 493:501 arg1 oil 562:564 rice bran oil 552:564 rice bran oil 552:564 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 34 theme vegetable 493:501 arg1 oils 503:506 vegetable oils 493:506 vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 493:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 34 theme vegetable 493:501 arg1 oil 517:519 soybean oil 509:519 soybean oil 509:519 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 34 theme vegetable 493:501 arg1 oil 547:549 cottonseed oil 536:549 cottonseed oil 536:549 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 34 theme vegetable 493:501 arg1 oil 580:582 camellia oil 571:582 camellia oil 571:582 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 35 theme camellia 571:578 arg1 oil 580:582 camellia oil 571:582 camellia oil 571:582 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 35 theme camellia 571:578 arg1 oils 503:506 vegetable oils 493:506 vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 493:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 3 36 theme thermal 850:856 arg1 stability 858:866 thermal stability 850:866 thermal stability 850:866 The relationships between the antioxidant capacity and thermal stability parameters were determined. 37297422 2 37 theme thermal 387:393 arg1 stability 405:413 the thermal oxidative stability 383:413 the thermal oxidative stability of different vegetable oils 383:441 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 38 theme oxidative 395:403 arg1 stability 405:413 the thermal oxidative stability 383:413 the thermal oxidative stability of different vegetable oils 383:441 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 4 39 theme thermal 1105:1111 arg1 rate 1132:1135 the thermal oxidation reaction rate 1101:1135 the thermal oxidation reaction rate (k) 1101:1139 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 39 theme thermal 1105:1111 arg1 oil 1185:1187 rice bran oil 1175:1187 rice bran oil 1175:1187 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 39 theme thermal 1105:1111 arg1 k 1138:1138 k 1138:1138 k 1138:1138 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 40 theme bran 1180:1183 arg1 rate 1132:1135 the thermal oxidation reaction rate 1101:1135 the thermal oxidation reaction rate (k) 1101:1139 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 40 theme bran 1180:1183 arg1 oil 1185:1187 rice bran oil 1175:1187 rice bran oil 1175:1187 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 3 41 theme capacity 837:844 arg1 parameters 868:877 the antioxidant capacity and thermal stability parameters 821:877 the antioxidant capacity and thermal stability parameters 821:877 The relationships between the antioxidant capacity and thermal stability parameters were determined. 37297422 2 42 theme oils 438:441 arg1 stability 405:413 the thermal oxidative stability 383:413 the thermal oxidative stability of different vegetable oils 383:441 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 5 43 theme RE 1430:1431 arg1 mechanism 1417:1425 the inhibition mechanism 1402:1425 the inhibition mechanism of RE 1402:1431 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 0 44 theme Rosemary 37:44 arg1 Extract 74:80 Rosemary (Rosmarinus officinalis L.) Extract 37:80 Rosemary (Rosmarinus officinalis L.) Extract 37:80 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 1 45 theme oil 266:268 arg1 oxidation 270:278 oil oxidation 266:278 oil oxidation 266:278 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 0 46 theme Oils 130:133 arg1 Stability 107:115 the Thermal Oxidative Stability 85:115 the Thermal Oxidative Stability of Vegetable Oils 85:133 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 4 47 theme rice 1175:1178 arg1 rate 1132:1135 the thermal oxidation reaction rate 1101:1135 the thermal oxidation reaction rate (k) 1101:1139 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 47 theme rice 1175:1178 arg1 oil 1185:1187 rice bran oil 1175:1187 rice bran oil 1175:1187 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 2 48 theme total 672:676 arg1 indices 619:625 the physicochemical indices 599:625 the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity) 599:732 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 48 theme total 672:676 arg1 content 687:693 total phenolic content 672:693 total phenolic content 672:693 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 5 49 theme oil 1441:1443 arg1 oxidation 1453:1461 oil thermal oxidation 1441:1461 oil thermal oxidation 1441:1461 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 4 50 theme scavenging 1002:1011 arg1 capacity 1013:1020 the free radical scavenging capacity 985:1020 the free radical scavenging capacity 985:1020 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 50 theme scavenging 1002:1011 arg1 Ea 1064:1065 Ea 1064:1065 Ea 1064:1065 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 0 51 theme Vegetable 120:128 arg1 Oils 130:133 Vegetable Oils 120:133 Vegetable Oils 120:133 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 5 52 theme correlation 1201:1211 arg1 analysis 1213:1220 A Spearman correlation analysis 1190:1220 A Spearman correlation analysis 1190:1220 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 2 53 theme RE 377:378 arg1 mechanism 364:372 mechanism 364:372 mechanism 364:372 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 53 theme RE 377:378 arg1 capacity 351:358 the protective capacity 336:358 the protective capacity 336:358 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 0 54 theme Rosmarinus 47:56 arg1 Rosemary 37:44 Rosemary 37:44 Rosemary (Rosmarinus officinalis L.) Extract 37:80 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 0 54 theme Rosmarinus 47:56 arg1 L. 70:71 Rosmarinus officinalis L. 47:71 Rosmarinus officinalis L. 47:71 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 2 55 dep oils 503:506 arg1 oil 531:533 rapeseed oil 522:533 rapeseed oil 522:533 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 55 dep oils 503:506 arg1 oil 562:564 rice bran oil 552:564 rice bran oil 552:564 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 55 dep oils 503:506 arg1 oils 503:506 vegetable oils 493:506 vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 493:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 55 dep oils 503:506 arg1 oil 517:519 soybean oil 509:519 soybean oil 509:519 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 55 dep oils 503:506 arg1 oil 547:549 cottonseed oil 536:549 cottonseed oil 536:549 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 55 dep oils 503:506 arg1 oil 580:582 camellia oil 571:582 camellia oil 571:582 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 56 theme physicochemical 603:617 arg1 content 663:669 tocopherol content 652:669 tocopherol content 652:669 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 56 theme physicochemical 603:617 arg1 indices 619:625 the physicochemical indices 599:625 the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity) 599:732 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 56 theme physicochemical 603:617 arg1 content 687:693 total phenolic content 672:693 total phenolic content 672:693 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 56 theme physicochemical 603:617 arg1 capacity 724:731 free radical scavenging capacity 700:731 free radical scavenging capacity 700:731 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 56 theme physicochemical 603:617 arg1 composition 639:649 fatty acid composition 628:649 fatty acid composition 628:649 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 57 theme present 311:317 arg1 study 319:323 The present study 307:323 The present study 307:323 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 58 theme vegetable 428:436 arg1 oils 438:441 different vegetable oils 418:441 different vegetable oils 418:441 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 59 theme soybean 509:515 arg1 oils 503:506 vegetable oils 493:506 vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 493:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 59 theme soybean 509:515 arg1 oil 517:519 soybean oil 509:519 soybean oil 509:519 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 4 60 theme oils 1158:1161 arg1 rate 1132:1135 the thermal oxidation reaction rate 1101:1135 the thermal oxidation reaction rate (k) 1101:1139 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 60 theme oils 1158:1161 arg1 oil 1185:1187 rice bran oil 1175:1187 rice bran oil 1175:1187 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 60 theme oils 1158:1161 arg1 k 1138:1138 k 1138:1138 k 1138:1138 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 3 61 theme stability 858:866 arg1 parameters 868:877 the antioxidant capacity and thermal stability parameters 821:877 the antioxidant capacity and thermal stability parameters 821:877 The relationships between the antioxidant capacity and thermal stability parameters were determined. 37297422 5 62 theme Spearman 1192:1199 arg1 correlation 1201:1211 A Spearman correlation 1190:1211 A Spearman correlation analysis 1190:1220 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 2 63 theme scavenging 713:722 arg1 indices 619:625 the physicochemical indices 599:625 the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity) 599:732 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 63 theme scavenging 713:722 arg1 capacity 724:731 free radical scavenging capacity 700:731 free radical scavenging capacity 700:731 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 4 64 theme vegetable 1148:1156 arg1 oils 1158:1161 all vegetable oils 1144:1161 all vegetable oils 1144:1161 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 5 65 theme thermal 1445:1451 arg1 oxidation 1453:1461 oil thermal oxidation 1441:1461 oil thermal oxidation 1441:1461 A Spearman correlation analysis showed that the induction period (IP) and Ea showed a significant positive correlation, the combination of which effectively reflected the efficiency of antioxidants and explained the inhibition mechanism of RE towards oil thermal oxidation. 37297422 2 66 from mechanism 364:372 arg1 stability 405:413 the thermal oxidative stability 383:413 the thermal oxidative stability of different vegetable oils 383:441 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 67 theme radical 705:711 arg1 indices 619:625 the physicochemical indices 599:625 the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity) 599:732 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 67 theme radical 705:711 arg1 capacity 724:731 free radical scavenging capacity 700:731 free radical scavenging capacity 700:731 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 68 theme thermal 757:763 arg1 parameters 783:792 thermal oxidative kinetic parameters 757:792 thermal oxidative kinetic parameters 757:792 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 69 theme oils 503:506 arg1 types 484:488 five types 479:488 five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 479:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 70 theme kinetic 775:781 arg1 parameters 783:792 thermal oxidative kinetic parameters 757:792 thermal oxidative kinetic parameters 757:792 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 4 71 theme induction 1023:1031 arg1 period 1033:1038 induction period 1023:1038 induction period 1023:1038 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 2 72 theme free 700:703 arg1 indices 619:625 the physicochemical indices 599:625 the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity) 599:732 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 72 theme free 700:703 arg1 capacity 724:731 free radical scavenging capacity 700:731 free radical scavenging capacity 700:731 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 73 theme % 459:459 arg1 acid 470:473 70% carnosic acid 457:473 70% carnosic acid 457:473 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 73 theme % 459:459 arg1 RE 453:454 RE 453:454 RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) 453:583 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 74 theme acid 634:637 arg1 indices 619:625 the physicochemical indices 599:625 the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity) 599:732 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 74 theme acid 634:637 arg1 composition 639:649 fatty acid composition 628:649 fatty acid composition 628:649 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 75 theme protective 340:349 arg1 capacity 351:358 the protective capacity 336:358 the protective capacity 336:358 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 4 76 theme radical 994:1000 arg1 capacity 1013:1020 the free radical scavenging capacity 985:1020 the free radical scavenging capacity 985:1020 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 4 76 theme radical 994:1000 arg1 Ea 1064:1065 Ea 1064:1065 Ea 1064:1065 The results show that, compared with artificial antioxidants, RE significantly increased the free radical scavenging capacity, induction period, and activation energy (Ea) of thermal oxidation, decreasing the thermal oxidation reaction rate (k) of all vegetable oils, especially rice bran oil. 37297422 0 77 theme officinalis 58:68 arg1 Rosemary 37:44 Rosemary 37:44 Rosemary (Rosmarinus officinalis L.) Extract 37:80 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 0 77 theme officinalis 58:68 arg1 L. 70:71 Rosmarinus officinalis L. 47:71 Rosmarinus officinalis L. 47:71 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 0 78 from Mechanism 24:32 arg1 Stability 107:115 the Thermal Oxidative Stability 85:115 the Thermal Oxidative Stability of Vegetable Oils 85:133 Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. 37297422 2 79 theme fatty 628:632 arg1 indices 619:625 the physicochemical indices 599:625 the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity) 599:732 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 2 79 theme fatty 628:632 arg1 composition 639:649 fatty acid composition 628:649 fatty acid composition 628:649 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 37297422 1 80 theme Rosemary 136:143 arg1 RE 182:183 RE 182:183 RE 182:183 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 1 80 theme Rosemary 136:143 arg1 extract 173:179 Rosemary (Rosmarinus officinalis L.) extract 136:179 Rosemary (Rosmarinus officinalis L.) extract (RE) 136:184 Rosemary (Rosmarinus officinalis L.) extract (RE) is one of the most efficient natural antioxidants and can significantly inhibit oil oxidation during storage or heating. 37297422 2 81 theme induction 735:743 arg1 period 745:750 induction period 735:750 induction period 735:750 The present study determined the protective capacity and mechanism of RE on the thermal oxidative stability of different vegetable oils by adding RE (70% carnosic acid) to five types of vegetable oils (soybean oil, rapeseed oil, cottonseed oil, rice bran oil, and camellia oil) and measuring the physicochemical indices (fatty acid composition, tocopherol content, total phenolic content, and free radical scavenging capacity), induction period, and thermal oxidative kinetic parameters. 35937804 10 0 theme transcriptome 1366:1378 arg1 data 1380:1383 NAT10 KD transcriptome and OGA KD transcriptome data 1332:1383 NAT10 KD transcriptome and OGA KD transcriptome data 1332:1383 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 13 1 theme maturation 1848:1857 arg1 mechanisms 1826:1835 the regulation mechanisms 1811:1835 the regulation mechanisms of oocytes maturation 1811:1857 Moreover, our study revealed the regulation mechanisms of oocytes maturation and provided reference for improving IVM outcomes. 35937804 1 2 theme follicle 238:245 arg1 fluid 247:251 follicle fluid 238:251 follicle fluid 238:251 In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. 35937804 14 3 theme maturation 2087:2096 arg1 network 2069:2075 the regulation network 2054:2075 the regulation network of oocyte maturation 2054:2096 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 13 4 theme regulation 1815:1824 arg1 mechanisms 1826:1835 the regulation mechanisms 1811:1835 the regulation mechanisms of oocytes maturation 1811:1857 Moreover, our study revealed the regulation mechanisms of oocytes maturation and provided reference for improving IVM outcomes. 35937804 3 5 theme cultivation 494:504 arg1 efficiency 506:515 the cultivation efficiency 490:515 the cultivation efficiency of IVM 490:522 However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. 35937804 3 5 theme cultivation 494:504 arg1 satisfactory 531:542 satisfactory 531:542 satisfactory 531:542 However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. 35937804 1 6 theme immature 156:163 arg1 oocytes 165:171 immature oocytes 156:171 immature oocytes 156:171 In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. 35937804 10 7 theme DNA 1516:1518 arg1 binding 1520:1526 nucleosome DNA binding 1505:1526 nucleosome DNA binding 1505:1526 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 5 8 theme important 809:817 arg1 gene 826:829 an important target gene 806:829 an important target gene for NAT10-mediated ac4C modification 806:866 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 5 8 theme important 809:817 arg1 O-GlcNAcase 785:795 O-GlcNAcase 785:795 O-GlcNAcase(OGA) 785:800 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 8 9 theme down 1130:1133 arg1 OGA 1135:1137 down OGA 1130:1137 down OGA of oocytes 1130:1148 After knocking down OGA of oocytes, oocyte maturation was inhibited. 35937804 4 10 theme oocyte 589:594 arg1 maturation 596:605 oocyte maturation 589:605 oocyte maturation 589:605 It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). 35937804 10 11 theme other 1533:1537 arg1 mechanisms 1539:1548 other mechanisms 1533:1548 other mechanisms 1533:1548 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 7 12 theme NAT10-mediated 1009:1022 arg1 ac4C 1024:1027 NAT10-mediated ac4C 1009:1027 NAT10-mediated ac4C 1009:1027 To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. 35937804 14 13 theme first 2027:2031 arg1 time 2033:2036 the first time 2023:2036 the first time 2023:2036 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 11 14 theme downstream 1640:1649 arg1 genes 1651:1655 potential downstream genes 1630:1655 potential downstream genes 1630:1655 Rsph6a, Gm7788, Gm41780, Trpc7, Gm29036, and Gm47144 were potential downstream genes. 35937804 5 15 theme oocyte 871:876 arg1 maturation 878:887 oocyte maturation 871:887 oocyte maturation 871:887 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 4 16 theme NAT10 650:654 arg1 KD 668:669 KD 668:669 KD 668:669 It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). 35937804 4 16 theme NAT10 650:654 arg1 knockdown 657:665 N-acetyltransferase 10 (NAT10) knockdown 626:665 N-acetyltransferase 10 (NAT10) knockdown (KD) 626:670 It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). 35937804 10 17 dep data 1380:1383 arg1 basis 1323:1327 basis 1323:1327 basis 1323:1327 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 10 17 dep data 1380:1383 arg1 the 1319:1321 the 1319:1321 the 1319:1321 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 10 18 theme molecular 1481:1489 arg1 transduction 1491:1502 molecular transduction 1481:1502 molecular transduction 1481:1502 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 10 19 theme OGA 1359:1361 arg1 KD 1363:1364 OGA KD 1359:1364 OGA KD 1359:1364 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 0 20 theme Oocyte 75:80 arg1 Maturation 82:91 Oocyte Maturation 75:91 Oocyte Maturation 75:91 NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation. 35937804 5 21 theme NAT10-mediated 835:848 arg1 modification 855:866 NAT10-mediated ac4C modification 835:866 NAT10-mediated ac4C modification 835:866 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 7 22 from role 1095:1098 arg1 IVM 1110:1112 IVM 1110:1112 IVM 1110:1112 To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. 35937804 10 23 theme transcriptome 1341:1353 arg1 KD 1338:1339 NAT10 KD transcriptome 1332:1353 NAT10 KD transcriptome 1332:1353 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 9 24 theme OGA 1217:1219 arg1 expression 1221:1230 OGA expression 1217:1230 OGA expression 1217:1230 In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. 35937804 2 25 with patients 287:294 arg1 syndrome 318:325 polycystic ovary syndrome 301:325 polycystic ovary syndrome 301:325 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 2 25 with patients 287:294 arg1 need 374:377 the need 370:377 the need of fertility preservation 370:403 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 2 26 theme fertility 382:390 arg1 preservation 392:403 fertility preservation 382:403 fertility preservation 382:403 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 14 27 theme protein 1979:1985 arg1 modification 1996:2007 protein O-GlcNAc modification 1979:2007 protein O-GlcNAc modification 1979:2007 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 10 28 theme oocyte 1553:1558 arg1 maturation 1560:1569 oocyte maturation 1553:1569 oocyte maturation 1553:1569 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 5 29 theme oocytes 762:768 arg1 alteration 733:742 the transcriptome alteration 715:742 the transcriptome alteration of NAT10-depleted oocytes 715:768 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 1 30 theme In 94:95 arg1 IVM 115:117 IVM 115:117 IVM 115:117 In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. 35937804 1 30 theme In 94:95 arg1 maturation 103:112 In vitro maturation 94:112 In vitro maturation (IVM) 94:118 In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. 35937804 14 31 located found 2013:2017 arg1 time 1922:1925 the same time 1913:1925 the same time 1913:1925 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 14 31 located found 2013:2017 arg2 interaction 1932:1942 the interaction 1928:1942 the interaction between mRNA ac4C modification and protein O-GlcNAc modification 1928:2007 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 2 32 theme preservation 392:403 arg1 need 374:377 the need 370:377 the need of fertility preservation 370:403 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 0 33 theme OGA 16:18 arg1 Stability 25:33 OGA mRNA Stability 16:33 OGA mRNA Stability 16:33 NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation. 35937804 14 34 theme mRNA 1952:1955 arg1 modification 1962:1973 mRNA ac4C modification 1952:1973 mRNA ac4C modification 1952:1973 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 5 35 theme transcriptome 719:731 arg1 alteration 733:742 the transcriptome alteration 715:742 the transcriptome alteration of NAT10-depleted oocytes 715:768 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 9 36 theme N-acetylglucosamine 1268:1286 arg1 level 1299:1303 O-linked N-acetylglucosamine (O-GlcNAc) level 1259:1303 O-linked N-acetylglucosamine (O-GlcNAc) level 1259:1303 In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. 35937804 12 37 theme OGA 1707:1709 arg1 transcript 1711:1720 OGA transcript 1707:1720 OGA transcript 1707:1720 In conclusion, NAT10 maintained the stability of OGA transcript by ac4C modification on it, thus positively regulating IVM. 35937804 0 38 theme ac4C 43:46 arg1 Modification 48:59 ac4C Modification 43:59 ac4C Modification 43:59 NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation. 35937804 12 39 theme ac4C 1725:1728 arg1 modification 1730:1741 ac4C modification 1725:1741 ac4C modification 1725:1741 In conclusion, NAT10 maintained the stability of OGA transcript by ac4C modification on it, thus positively regulating IVM. 35937804 2 40 theme ovary 312:316 arg1 syndrome 318:325 polycystic ovary syndrome 301:325 polycystic ovary syndrome 301:325 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 10 41 from transduction 1491:1502 arg1 maturation 1560:1569 oocyte maturation 1553:1569 oocyte maturation 1553:1569 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 10 42 theme protein-coupled 1454:1468 arg1 receptors 1470:1478 G protein-coupled receptors 1452:1478 G protein-coupled receptors 1452:1478 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 2 43 with patients 356:363 arg1 syndrome 318:325 polycystic ovary syndrome 301:325 polycystic ovary syndrome 301:325 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 2 43 with patients 356:363 arg1 need 374:377 the need 370:377 the need of fertility preservation 370:403 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 7 44 from influence 996:1004 arg1 maturation 1039:1048 oocyte maturation 1032:1048 oocyte maturation 1032:1048 To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. 35937804 10 45 from binding 1520:1526 arg1 maturation 1560:1569 oocyte maturation 1553:1569 oocyte maturation 1553:1569 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 10 46 theme ac4C 1401:1404 arg1 modification 1406:1417 NAT10-mediated ac4C modification 1386:1417 NAT10-mediated ac4C modification of OGA 1386:1424 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 10 47 mod modification 1406:1417 arg3 ac4C 1401:1404 NAT10-mediated ac4C modification 1386:1417 NAT10-mediated ac4C modification of OGA 1386:1424 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 10 47 mod modification 1406:1417 arg1 OGA 1422:1424 OGA 1422:1424 OGA 1422:1424 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 2 48 theme important 263:271 arg1 It 254:255 It 254:255 It 254:255 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 2 48 theme important 263:271 arg1 technique 273:281 an important technique 260:281 an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation 260:403 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 14 49 theme oocyte 2080:2085 arg1 maturation 2087:2096 oocyte maturation 2080:2096 oocyte maturation 2080:2096 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 10 50 from mechanisms 1539:1548 arg1 maturation 1560:1569 oocyte maturation 1553:1569 oocyte maturation 1553:1569 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 14 51 theme regulation 2058:2067 arg1 network 2069:2075 the regulation network 2054:2075 the regulation network of oocyte maturation 2054:2096 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 8 52 theme oocyte 1151:1156 arg1 maturation 1158:1167 oocyte maturation 1151:1167 oocyte maturation 1151:1167 After knocking down OGA of oocytes, oocyte maturation was inhibited. 35937804 7 53 theme oocyte 1032:1037 arg1 maturation 1039:1048 oocyte maturation 1032:1048 oocyte maturation 1032:1048 To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. 35937804 4 54 theme N-acetyltransferase 626:644 arg1 KD 668:669 KD 668:669 KD 668:669 It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). 35937804 4 54 theme N-acetyltransferase 626:644 arg1 knockdown 657:665 N-acetyltransferase 10 (NAT10) knockdown 626:665 N-acetyltransferase 10 (NAT10) knockdown (KD) 626:670 It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). 35937804 10 55 theme nucleosome 1505:1514 arg1 binding 1520:1526 nucleosome DNA binding 1505:1526 nucleosome DNA binding 1505:1526 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 7 56 theme ac4C 1024:1027 arg1 influence 996:1004 the influence 992:1004 the influence of NAT10-mediated ac4C on oocyte maturation 992:1048 To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. 35937804 13 57 theme oocytes 1840:1846 arg1 maturation 1848:1857 oocytes maturation 1840:1857 oocytes maturation 1840:1857 Moreover, our study revealed the regulation mechanisms of oocytes maturation and provided reference for improving IVM outcomes. 35937804 3 58 theme IVM 520:522 arg1 efficiency 506:515 the cultivation efficiency 490:515 the cultivation efficiency of IVM 490:522 However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. 35937804 3 58 theme IVM 520:522 arg1 satisfactory 531:542 satisfactory 531:542 satisfactory 531:542 However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. 35937804 5 59 theme ac4C 850:853 arg1 modification 855:866 NAT10-mediated ac4C modification 835:866 NAT10-mediated ac4C modification 835:866 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 8 60 theme oocytes 1142:1148 arg1 OGA 1135:1137 down OGA 1130:1137 down OGA of oocytes 1130:1148 After knocking down OGA of oocytes, oocyte maturation was inhibited. 35937804 6 61 dep OGA 911:913 arg1 stability 915:923 stability 915:923 stability 915:923 NAT10 might regulate OGA stability and expression by suppressing its degradation. 35937804 3 62 theme maturation 443:452 arg1 mechanisms 422:431 the mechanisms 418:431 the mechanisms of oocyte maturation 418:452 However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. 35937804 5 63 theme target 819:824 arg1 gene 826:829 an important target gene 806:829 an important target gene for NAT10-mediated ac4C modification 806:866 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 5 63 theme target 819:824 arg1 O-GlcNAcase 785:795 O-GlcNAcase 785:795 O-GlcNAcase(OGA) 785:800 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 11 64 theme potential 1630:1638 arg1 genes 1651:1655 potential downstream genes 1630:1655 potential downstream genes 1630:1655 Rsph6a, Gm7788, Gm41780, Trpc7, Gm29036, and Gm47144 were potential downstream genes. 35937804 1 65 dep In 94:95 arg1 vitro 97:101 vitro 97:101 vitro 97:101 In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. 35937804 14 66 theme same 1917:1920 arg1 time 1922:1925 the same time 1913:1925 the same time 1913:1925 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 10 67 theme KD 1338:1339 arg1 data 1380:1383 NAT10 KD transcriptome and OGA KD transcriptome data 1332:1383 NAT10 KD transcriptome and OGA KD transcriptome data 1332:1383 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 5 68 theme present 680:686 arg1 study 688:692 the present study 676:692 the present study 676:692 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 5 69 from gene 826:829 arg1 maturation 878:887 oocyte maturation 871:887 oocyte maturation 871:887 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 14 70 theme O-GlcNAc 1987:1994 arg1 modification 1996:2007 protein O-GlcNAc modification 1979:2007 protein O-GlcNAc modification 1979:2007 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 5 71 theme NAT10-depleted 747:760 arg1 oocytes 762:768 NAT10-depleted oocytes 747:768 NAT10-depleted oocytes 747:768 In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. 35937804 10 72 theme KD 1363:1364 arg1 data 1380:1383 NAT10 KD transcriptome and OGA KD transcriptome data 1332:1383 NAT10 KD transcriptome and OGA KD transcriptome data 1332:1383 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 2 73 theme young 350:354 arg1 patients 356:363 those young patients 344:363 those young patients with the need of fertility preservation 344:403 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 0 74 theme mRNA 20:23 arg1 Stability 25:33 OGA mRNA Stability 16:33 OGA mRNA Stability 16:33 NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation. 35937804 14 75 theme ac4C 1957:1960 arg1 modification 1962:1973 mRNA ac4C modification 1952:1973 mRNA ac4C modification 1952:1973 At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. 35937804 3 76 theme oocyte 436:441 arg1 maturation 443:452 oocyte maturation 436:452 oocyte maturation 436:452 However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. 35937804 9 77 theme O-linked 1259:1266 arg1 O-GlcNAc 1289:1296 O-GlcNAc 1289:1296 O-GlcNAc 1289:1296 In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. 35937804 9 77 theme O-linked 1259:1266 arg1 N-acetylglucosamine 1268:1286 O-linked N-acetylglucosamine 1259:1286 O-linked N-acetylglucosamine (O-GlcNAc) level 1259:1303 In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. 35937804 10 78 theme NAT10-mediated 1386:1399 arg1 modification 1406:1417 NAT10-mediated ac4C modification 1386:1417 NAT10-mediated ac4C modification of OGA 1386:1424 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 10 79 from receptors 1470:1478 arg1 maturation 1560:1569 oocyte maturation 1553:1569 oocyte maturation 1553:1569 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 12 80 theme transcript 1711:1720 arg1 stability 1694:1702 the stability 1690:1702 the stability of OGA transcript 1690:1720 In conclusion, NAT10 maintained the stability of OGA transcript by ac4C modification on it, thus positively regulating IVM. 35937804 10 81 theme OGA 1422:1424 arg1 modification 1406:1417 NAT10-mediated ac4C modification 1386:1417 NAT10-mediated ac4C modification of OGA 1386:1424 On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. 35937804 2 82 theme polycystic 301:310 arg1 syndrome 318:325 polycystic ovary syndrome 301:325 polycystic ovary syndrome 301:325 It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. 35937804 9 83 link O-linked 1259:1266 arg1 O-GlcNAc 1289:1296 O-GlcNAc 1289:1296 O-GlcNAc 1289:1296 In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. 35937804 9 83 link O-linked 1259:1266 arg1 N-acetylglucosamine 1268:1286 O-linked N-acetylglucosamine 1259:1286 O-linked N-acetylglucosamine (O-GlcNAc) level 1259:1303 In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. 35937804 4 84 theme previous 569:576 arg1 study 578:582 our previous study 565:582 our previous study 565:582 It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). 35937804 13 85 theme IVM 1896:1898 arg1 outcomes 1900:1907 IVM outcomes 1896:1907 IVM outcomes 1896:1907 Moreover, our study revealed the regulation mechanisms of oocytes maturation and provided reference for improving IVM outcomes. 35937804 7 86 theme OGA 1103:1105 arg1 role 1095:1098 the role 1091:1098 the role of OGA in IVM 1091:1112 To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. 35937804 1 87 theme analogous 225:233 arg1 microenvironment 208:223 the microenvironment 204:223 the microenvironment analogous to follicle fluid 204:251 In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. 36260507 8 0 theme unidentified 1087:1098 arg1 lipids 1100:1105 five unidentified lipids 1082:1105 five unidentified lipids 1082:1105 The polar lipid profile consisted of phosphatidylethanolamine and five unidentified lipids. 36260507 6 1 theme orthologous 763:773 arg1 identity 794:801 The highest orthologous average nucleotide identity 751:801 The highest orthologous average nucleotide identity (OrthoANI) values 751:819 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 6 1 theme orthologous 763:773 arg1 OrthoANI 804:811 OrthoANI 804:811 OrthoANI 804:811 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 11 2 theme draft 1298:1302 arg1 6.25 Mb 1312:1318 6.25 Mb 1312:1318 6.25 Mb 1312:1318 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 2 theme draft 1298:1302 arg1 genome 1304:1309 The draft genome 1294:1309 The draft genome (6.25 Mb) of strain CC-SYL272T 1294:1340 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 6 3 theme strain 839:844 arg1 CC-SYL272T 846:855 strain CC-SYL272T versus Niabella species 839:879 CC-SYL272T 846:855 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 13 4 theme 16S 1672:1674 arg1 rRNA 1676:1679 comparative 16S rRNA 1660:1679 comparative 16S rRNA gene sequence 1660:1693 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 11 5 theme rRNA 1430:1433 arg1 genes 1420:1424 5087 protein-encoding genes 1398:1424 5087 protein-encoding genes 1398:1424 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 5 theme rRNA 1430:1433 arg1 genes 1435:1439 10 rRNA genes 1427:1439 10 rRNA genes 1427:1439 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 5 6 theme rRNA 469:472 arg1 sequences 479:487 16S rRNA gene sequences 465:487 16S rRNA gene sequences 465:487 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 3 7 theme non-motile 261:270 arg1 rods 294:297 aerobic, non-motile and non-spore-forming rods 252:297 aerobic, non-motile and non-spore-forming rods 252:297 Cells were observed to be strictly aerobic, non-motile and non-spore-forming rods, exhibiting positive catalase and oxidase. 36260507 10 8 theme  1 1286:1287 arg1 ω7c 1289:1291  1 ω7c 1286:1291 iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c 1221:1291 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 11 9 theme CC-SYL272T 1331:1340 arg1 6.25 Mb 1312:1318 6.25 Mb 1312:1318 6.25 Mb 1312:1318 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 9 theme CC-SYL272T 1331:1340 arg1 genome 1304:1309 The draft genome 1294:1309 The draft genome (6.25 Mb) of strain CC-SYL272T 1294:1340 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 3 10 theme aerobic 252:258 arg1 rods 294:297 aerobic, non-motile and non-spore-forming rods 252:297 aerobic, non-motile and non-spore-forming rods 252:297 Cells were observed to be strictly aerobic, non-motile and non-spore-forming rods, exhibiting positive catalase and oxidase. 36260507 2 11 theme taxonomic 67:75 arg1 approach 77:84 A polyphasic taxonomic approach 54:84 A polyphasic taxonomic approach 54:84 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 3 12 theme non-spore-forming 276:292 arg1 rods 294:297 aerobic, non-motile and non-spore-forming rods 252:297 aerobic, non-motile and non-spore-forming rods 252:297 Cells were observed to be strictly aerobic, non-motile and non-spore-forming rods, exhibiting positive catalase and oxidase. 36260507 11 13 theme 47.1 mol 1371:1378 arg1 genes 1420:1424 5087 protein-encoding genes 1398:1424 5087 protein-encoding genes 1398:1424 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 13 theme 47.1 mol 1371:1378 arg1 content 1389:1395 47.1 mol% DNA G+C content 1371:1395 47.1 mol% DNA G+C content 1371:1395 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 7 14 theme strain 966:971 arg1 CC-SYL272T 973:982 strain CC-SYL272T 966:982 strain CC-SYL272T against N. pedocola 966:1002 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. 36260507 7 15 theme hybridization 926:938 arg1 % 1013:1013 27.3 % 1008:1013 27.3 % 1008:1013 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. 36260507 7 15 theme hybridization 926:938 arg1 value 947:951 The mean digital DNA-DNA hybridization (dDDH) value 901:951 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola 901:1002 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. 36260507 4 16 theme NaCl 416:419 arg1 w/v 428:430 w/v 428:430 w/v 428:430 Strain CC-SYL272T was found to grow optimally at 20-40 °C, pH 6.0-8.0 and NaCl 0-2 % (w/v). 36260507 4 16 theme NaCl 416:419 arg1 % 425:425 NaCl 0-2 % 416:425 NaCl 0-2 % (w/v) 416:431 Strain CC-SYL272T was found to grow optimally at 20-40 °C, pH 6.0-8.0 and NaCl 0-2 % (w/v). 36260507 10 17 theme cellular 1184:1191 arg1 acids 1199:1203 The dominating cellular fatty acids 1169:1203 The dominating cellular fatty acids (>5 %) 1169:1210 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 10 17 theme cellular 1184:1191 arg1 % 1209:1209 >5 % 1206:1209 >5 % 1206:1209 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 5 18 theme distinct 693:700 arg1 lineage 712:718 a distinct taxonomic lineage 691:718 a distinct taxonomic lineage associated with these species 691:748 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 7 19 theme digital 910:916 arg1 hybridization 926:938 digital DNA-DNA hybridization 910:938 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola 901:1002 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. 36260507 7 19 theme digital 910:916 arg1 dDDH 941:944 dDDH 941:944 dDDH 941:944 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. 36260507 12 20 theme plant 1539:1543 arg1 depolymerization 1503:1518 the depolymerization 1499:1518 the depolymerization of both animal and plant polysaccharides 1499:1559 The genome harboured genes involved in the depolymerization of both animal and plant polysaccharides. 36260507 3 21 theme positive 311:318 arg1 catalase 320:327 positive catalase 311:327 positive catalase 311:327 Cells were observed to be strictly aerobic, non-motile and non-spore-forming rods, exhibiting positive catalase and oxidase. 36260507 11 22 theme DNA 1381:1383 arg1 genes 1420:1424 5087 protein-encoding genes 1398:1424 5087 protein-encoding genes 1398:1424 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 22 theme DNA 1381:1383 arg1 content 1389:1395 47.1 mol% DNA G+C content 1371:1395 47.1 mol% DNA G+C content 1371:1395 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 13 23 theme Niabella 1889:1896 arg1 sp 1907:1908 the name Niabella agricola sp 1880:1908 the name Niabella agricola sp 1880:1908 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 13 24 theme phylogenomic 1719:1730 arg1 placement 1732:1740 the phylogenomic placement 1715:1740 the phylogenomic placement 1715:1740 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 5 25 theme genus 537:541 arg1 Niabella 543:550 the genus Niabella 533:550 the genus Niabella 533:550 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 5 25 theme genus 537:541 arg1 Chitinophagaceae 560:575 family Chitinophagaceae 553:575 family Chitinophagaceae 553:575 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 12 26 theme animal 1528:1533 arg1 depolymerization 1503:1518 the depolymerization 1499:1518 the depolymerization of both animal and plant polysaccharides 1499:1559 The genome harboured genes involved in the depolymerization of both animal and plant polysaccharides. 36260507 0 27 theme Niabella 0:7 arg1 sp 18:19 Niabella agricola sp 0:19 Niabella agricola sp. 0:20 Niabella agricola sp. 36260507 2 28 attach isolated 191:198 arg2 bacterium 150:158 a Gram-stain-negative, orange-coloured bacterium 111:158 a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil 111:214 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 2 28 attach isolated 191:198 arg1 soil 211:214 paddy soil 205:214 paddy soil 205:214 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 2 28 attach isolated 191:198 arg2 CC-SYL272T 179:188 designated strain CC-SYL272T 161:188 designated strain CC-SYL272T 161:188 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 2 29 dep Gram-stain-negative 113:131 arg1 orange-coloured 134:148 orange-coloured 134:148 orange-coloured 134:148 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 2 30 used used 90:93 arg2 approach 77:84 A polyphasic taxonomic approach 54:84 A polyphasic taxonomic approach 54:84 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 2 31 theme strain 172:177 arg1 CC-SYL272T 179:188 designated strain CC-SYL272T 161:188 designated strain CC-SYL272T 161:188 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 2 31 theme strain 172:177 arg1 bacterium 150:158 a Gram-stain-negative, orange-coloured bacterium 111:158 a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil 111:214 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 11 32 theme strain 1324:1329 arg1 CC-SYL272T 1331:1340 strain CC-SYL272T 1324:1340 strain CC-SYL272T 1324:1340 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 15 33 theme 81319T=JCM 1966:1975 arg1 34758T 1977:1982 =BCRC 81319T=JCM 34758T 1960:1982 =BCRC 81319T=JCM 34758T 1960:1982 The type strain is CC-SYL272T (=BCRC 81319T=JCM 34758T). 36260507 15 33 theme 81319T=JCM 1966:1975 arg1 CC-SYL272T 1948:1957 CC-SYL272T 1948:1957 CC-SYL272T (=BCRC 81319T=JCM 34758T) 1948:1983 The type strain is CC-SYL272T (=BCRC 81319T=JCM 34758T). 36260507 4 34 theme Strain 342:347 arg1 CC-SYL272T 349:358 Strain CC-SYL272T 342:358 Strain CC-SYL272T 342:358 Strain CC-SYL272T was found to grow optimally at 20-40 °C, pH 6.0-8.0 and NaCl 0-2 % (w/v). 36260507 8 35 theme lipid 1026:1030 arg1 profile 1032:1038 The polar lipid profile 1016:1038 The polar lipid profile 1016:1038 The polar lipid profile consisted of phosphatidylethanolamine and five unidentified lipids. 36260507 13 36 theme name 1884:1887 arg1 sp 1907:1908 the name Niabella agricola sp 1880:1908 the name Niabella agricola sp 1880:1908 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 6 37 theme nucleotide 783:792 arg1 identity 794:801 The highest orthologous average nucleotide identity 751:801 The highest orthologous average nucleotide identity (OrthoANI) values 751:819 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 6 37 theme nucleotide 783:792 arg1 OrthoANI 804:811 OrthoANI 804:811 OrthoANI 804:811 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 10 38 theme  0 1258:1259 arg1 3OH 1261:1263  0 3OH 1258:1263  0 3OH 1258:1263 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 13 39 theme rRNA 1676:1679 arg1 sequence 1686:1693 comparative 16S rRNA gene sequence 1660:1693 comparative 16S rRNA gene sequence 1660:1693 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 13 40 theme family 1845:1850 arg1 Chitinophagaceae 1852:1867 the family Chitinophagaceae 1841:1867 the family Chitinophagaceae 1841:1867 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 13 41 theme novel 1790:1794 arg1 species 1796:1802 a novel species 1788:1802 a novel species 1788:1802 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 13 42 theme sequence 1686:1693 arg1 results 1649:1655 results 1649:1655 results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement 1649:1740 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 5 43 theme Niabella 609:616 arg1 pedocola 618:625 Niabella pedocola 609:625 Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species 609:748 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 5 43 theme Niabella 609:616 arg1 % 633:633 97.8 % 628:633 97.8 % 628:633 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 9 44 theme major 1112:1116 arg1 putrescine 1134:1143 putrescine 1134:1143 putrescine 1134:1143 The major polyamines were putrescine and sym-homospermidine. 36260507 9 44 theme major 1112:1116 arg1 polyamines 1118:1127 The major polyamines 1108:1127 The major polyamines 1108:1127 The major polyamines were putrescine and sym-homospermidine. 36260507 10 45 theme dominating 1173:1182 arg1 acids 1199:1203 The dominating cellular fatty acids 1169:1203 The dominating cellular fatty acids (>5 %) 1169:1210 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 10 45 theme dominating 1173:1182 arg1 % 1209:1209 >5 % 1206:1209 >5 % 1206:1209 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 6 46 theme Niabella 864:871 arg1 species 873:879 strain CC-SYL272T versus Niabella species 839:879 species 873:879 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 6 47 theme highest 755:761 arg1 identity 794:801 The highest orthologous average nucleotide identity 751:801 The highest orthologous average nucleotide identity (OrthoANI) values 751:819 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 6 47 theme highest 755:761 arg1 OrthoANI 804:811 OrthoANI 804:811 OrthoANI 804:811 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 13 48 theme Niabella 1817:1824 arg1 species 1796:1802 a novel species 1788:1802 a novel species 1788:1802 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 7 49 theme DNA-DNA 918:924 arg1 hybridization 926:938 digital DNA-DNA hybridization 910:938 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola 901:1002 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. 36260507 7 49 theme DNA-DNA 918:924 arg1 dDDH 941:944 dDDH 941:944 dDDH 941:944 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. 36260507 13 50 theme comparative 1660:1670 arg1 rRNA 1676:1679 comparative 16S rRNA 1660:1679 comparative 16S rRNA gene sequence 1660:1693 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 10 51 theme  1 1274:1275 arg1 ω6c/C16  1277:1284  1 ω6c/C16  1274:1284 iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c 1221:1291 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 5 52 theme 16S 465:467 arg1 sequences 479:487 16S rRNA gene sequences 465:487 16S rRNA gene sequences 465:487 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 13 53 theme chemotaxonomic 1613:1626 arg1 traits 1628:1633 its distinct phylogenetic, phenotypic and chemotaxonomic traits 1571:1633 its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement 1571:1740 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 2 54 theme Gram-stain-negative 113:131 arg1 CC-SYL272T 179:188 designated strain CC-SYL272T 161:188 designated strain CC-SYL272T 161:188 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 2 54 theme Gram-stain-negative 113:131 arg1 bacterium 150:158 a Gram-stain-negative, orange-coloured bacterium 111:158 a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil 111:214 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 5 55 theme gene 474:477 arg1 sequences 479:487 16S rRNA gene sequences 465:487 16S rRNA gene sequences 465:487 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 5 56 theme Niabella 648:655 arg1 drilacis 657:664 Niabella drilacis 648:664 Niabella drilacis (97.2 %) 648:673 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 5 56 theme Niabella 648:655 arg1 % 672:672 97.2 % 667:672 97.2 % 667:672 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 13 57 theme genus 1811:1815 arg1 Niabella 1817:1824 the genus Niabella 1807:1824 the genus Niabella 1807:1824 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 5 58 theme Phylogenetic 434:445 arg1 analysis 447:454 Phylogenetic analysis 434:454 Phylogenetic analysis based on 16S rRNA gene sequences 434:487 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 13 59 theme phylogenetic 1584:1595 arg1 traits 1628:1633 its distinct phylogenetic, phenotypic and chemotaxonomic traits 1571:1633 its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement 1571:1740 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 7 60 theme N. 992:993 arg1 pedocola 995:1002 N. pedocola 992:1002 N. pedocola 992:1002 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. 36260507 13 61 theme phenotypic 1598:1607 arg1 traits 1628:1633 its distinct phylogenetic, phenotypic and chemotaxonomic traits 1571:1633 its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement 1571:1740 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 2 62 theme polyphasic 56:65 arg1 approach 77:84 A polyphasic taxonomic approach 54:84 A polyphasic taxonomic approach 54:84 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 10 63 theme fatty 1193:1197 arg1 acids 1199:1203 The dominating cellular fatty acids 1169:1203 The dominating cellular fatty acids (>5 %) 1169:1210 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 10 63 theme fatty 1193:1197 arg1 % 1209:1209 >5 % 1206:1209 >5 % 1206:1209 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 10 64 dep iso-C15  1221:1228 arg1 3OH 1261:1263  0 3OH 1258:1263  0 3OH 1258:1263 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 10 64 dep iso-C15  1221:1228 arg1 G 1246:1246 iso-C15 : 1 G 1234:1246 iso-C15 : 1 G 1234:1246 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 10 64 dep iso-C15  1221:1228 arg1 C16  1269:1272 C16  1269:1272 C16  1269:1272 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 10 64 dep iso-C15  1221:1228 arg1 ω7c 1289:1291  1 ω7c 1286:1291 iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c 1221:1291 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 10 64 dep iso-C15  1221:1228 arg1  0 1230:1231  0 1230:1231  0 1230:1231 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 10 64 dep iso-C15  1221:1228 arg1 iso-C17  1249:1256 iso-C17  1249:1256 iso-C17  1249:1256 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 10 64 dep iso-C15  1221:1228 arg1 ω6c/C16  1277:1284  1 ω6c/C16  1274:1284 iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c 1221:1291 The dominating cellular fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3OH and C16 : 1 ω6c/C16 : 1 ω7c. 36260507 13 65 theme strain 1743:1748 arg1 CC-SYL272T 1750:1759 strain CC-SYL272T 1743:1759 strain CC-SYL272T 1743:1759 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 5 66 theme taxonomic 702:710 arg1 lineage 712:718 a distinct taxonomic lineage 691:718 a distinct taxonomic lineage associated with these species 691:748 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 5 67 theme strain 504:509 arg1 CC-SYL272T 511:520 strain CC-SYL272T 504:520 strain CC-SYL272T 504:520 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 11 68 theme % 1379:1379 arg1 genes 1420:1424 5087 protein-encoding genes 1398:1424 5087 protein-encoding genes 1398:1424 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 68 theme % 1379:1379 arg1 content 1389:1395 47.1 mol% DNA G+C content 1371:1395 47.1 mol% DNA G+C content 1371:1395 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 7 69 theme mean 905:908 arg1 % 1013:1013 27.3 % 1008:1013 27.3 % 1008:1013 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. 36260507 7 69 theme mean 905:908 arg1 value 947:951 The mean digital DNA-DNA hybridization (dDDH) value 901:951 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola 901:1002 The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-SYL272T against N. pedocola was 27.3 %. 36260507 1 70 theme paddy 42:46 arg1 soil 48:51 paddy soil 42:51 paddy soil 42:51 nov., isolated from paddy soil. 36260507 13 71 theme distinct 1575:1582 arg1 traits 1628:1633 its distinct phylogenetic, phenotypic and chemotaxonomic traits 1571:1633 its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement 1571:1740 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 13 72 theme agricola 1898:1905 arg1 sp 1907:1908 the name Niabella agricola sp 1880:1908 the name Niabella agricola sp 1880:1908 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 11 73 theme G+C 1385:1387 arg1 genes 1420:1424 5087 protein-encoding genes 1398:1424 5087 protein-encoding genes 1398:1424 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 73 theme G+C 1385:1387 arg1 content 1389:1395 47.1 mol% DNA G+C content 1371:1395 47.1 mol% DNA G+C content 1371:1395 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 13 74 theme placement 1732:1740 arg1 results 1649:1655 results 1649:1655 results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement 1649:1740 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 0 75 theme agricola 9:16 arg1 sp 18:19 Niabella agricola sp 0:19 Niabella agricola sp. 0:20 Niabella agricola sp. 36260507 11 76 theme protein-encoding 1403:1418 arg1 genes 1453:1457 44 tRNA genes 1445:1457 44 tRNA genes 1445:1457 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 76 theme protein-encoding 1403:1418 arg1 genes 1420:1424 5087 protein-encoding genes 1398:1424 5087 protein-encoding genes 1398:1424 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 76 theme protein-encoding 1403:1418 arg1 content 1389:1395 47.1 mol% DNA G+C content 1371:1395 47.1 mol% DNA G+C content 1371:1395 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 76 theme protein-encoding 1403:1418 arg1 genes 1435:1439 10 rRNA genes 1427:1439 10 rRNA genes 1427:1439 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 6 77 theme average 775:781 arg1 identity 794:801 The highest orthologous average nucleotide identity 751:801 The highest orthologous average nucleotide identity (OrthoANI) values 751:819 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 6 77 theme average 775:781 arg1 OrthoANI 804:811 OrthoANI 804:811 OrthoANI 804:811 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 13 78 theme OrthoANI 1696:1703 arg1 results 1649:1655 results 1649:1655 results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement 1649:1740 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 5 79 theme family 553:558 arg1 Niabella 543:550 the genus Niabella 533:550 the genus Niabella 533:550 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 5 79 theme family 553:558 arg1 Chitinophagaceae 560:575 family Chitinophagaceae 553:575 family Chitinophagaceae 553:575 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 5 80 dep pedocola 618:625 arg1 followed 636:643 followed 636:643 followed by Niabella drilacis (97.2 %) 636:673 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 5 80 dep pedocola 618:625 arg1 established 679:689 established 679:689 established a distinct taxonomic lineage associated with these species 679:748 Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CC-SYL272T belongs to the genus Niabella, family Chitinophagaceae, and is most closely related to Niabella pedocola (97.8 %) followed by Niabella drilacis (97.2 %) and established a distinct taxonomic lineage associated with these species. 36260507 13 81 theme dDDH 1706:1709 arg1 results 1649:1655 results 1649:1655 results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement 1649:1740 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 36260507 8 82 theme polar 1020:1024 arg1 profile 1032:1038 The polar lipid profile 1016:1038 The polar lipid profile 1016:1038 The polar lipid profile consisted of phosphatidylethanolamine and five unidentified lipids. 36260507 15 83 theme =BCRC 1960:1964 arg1 34758T 1977:1982 =BCRC 81319T=JCM 34758T 1960:1982 =BCRC 81319T=JCM 34758T 1960:1982 The type strain is CC-SYL272T (=BCRC 81319T=JCM 34758T). 36260507 15 83 theme =BCRC 1960:1964 arg1 CC-SYL272T 1948:1957 CC-SYL272T 1948:1957 CC-SYL272T (=BCRC 81319T=JCM 34758T) 1948:1983 The type strain is CC-SYL272T (=BCRC 81319T=JCM 34758T). 36260507 2 84 theme designated 161:170 arg1 CC-SYL272T 179:188 designated strain CC-SYL272T 161:188 designated strain CC-SYL272T 161:188 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 2 84 theme designated 161:170 arg1 bacterium 150:158 a Gram-stain-negative, orange-coloured bacterium 111:158 a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil 111:214 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 11 85 theme tRNA 1448:1451 arg1 genes 1420:1424 5087 protein-encoding genes 1398:1424 5087 protein-encoding genes 1398:1424 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 85 theme tRNA 1448:1451 arg1 genes 1453:1457 44 tRNA genes 1445:1457 44 tRNA genes 1445:1457 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 2 86 theme paddy 205:209 arg1 soil 211:214 paddy soil 205:214 paddy soil 205:214 A polyphasic taxonomic approach was used to characterize a Gram-stain-negative, orange-coloured bacterium (designated strain CC-SYL272T) isolated from paddy soil. 36260507 15 87 theme type 1933:1936 arg1 strain 1938:1943 The type strain 1929:1943 The type strain 1929:1943 The type strain is CC-SYL272T (=BCRC 81319T=JCM 34758T). 36260507 15 87 theme type 1933:1936 arg1 CC-SYL272T 1948:1957 CC-SYL272T 1948:1957 CC-SYL272T (=BCRC 81319T=JCM 34758T) 1948:1983 The type strain is CC-SYL272T (=BCRC 81319T=JCM 34758T). 36260507 6 88 theme identity 794:801 arg1 values 814:819 The highest orthologous average nucleotide identity (OrthoANI) values 751:819 The highest orthologous average nucleotide identity (OrthoANI) values 751:819 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 12 89 dep animal 1528:1533 arg1 polysaccharides 1545:1559 polysaccharides 1545:1559 polysaccharides 1545:1559 The genome harboured genes involved in the depolymerization of both animal and plant polysaccharides. 36260507 11 90 contain having 1364:1369 arg2 content 1389:1395 47.1 mol% DNA G+C content 1371:1395 47.1 mol% DNA G+C content 1371:1395 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 90 contain having 1364:1369 arg2 genes 1420:1424 5087 protein-encoding genes 1398:1424 5087 protein-encoding genes 1398:1424 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 11 90 contain having 1364:1369 arg1 contigs 1356:1362 three contigs 1350:1362 three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes 1350:1457 The draft genome (6.25 Mb) of strain CC-SYL272T spanned three contigs having 47.1 mol% DNA G+C content, 5087 protein-encoding genes, 10 rRNA genes and 44 tRNA genes. 36260507 6 91 dep CC-SYL272T 846:855 arg1 n=8 895:897 n=8 895:897 n=8 895:897 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 6 91 dep CC-SYL272T 846:855 arg1 % 892:892 69.1-83.5 % 882:892 69.1-83.5 % 882:892 The highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-SYL272T versus Niabella species (69.1-83.5 %, n=8). 36260507 13 92 theme gene 1681:1684 arg1 sequence 1686:1693 comparative 16S rRNA gene sequence 1660:1693 comparative 16S rRNA gene sequence 1660:1693 Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH and the phylogenomic placement, strain CC-SYL272T is considered to represent a novel species of the genus Niabella, affiliated to the family Chitinophagaceae, for which the name Niabella agricola sp. 37152609 9 0 theme O-GlcNAc 1649:1656 arg1 modification 1658:1669 hippocampal O-GlcNAc modification 1637:1669 hippocampal O-GlcNAc modification 1637:1669 In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. 37152609 2 1 theme previous 405:412 arg1 studies 414:420 Our previous studies 401:420 Our previous studies 401:420 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 4 2 theme LW 887:888 arg1 treatment 890:898 LW treatment 887:898 LW treatment 887:898 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 7 3 from abundance 1297:1305 arg1 mice 1367:1370 CUMS mice 1362:1370 CUMS mice 1362:1370 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 1 4 theme O-linked 214:221 arg1 O-GlcNAc 249:256 O-GlcNAc 249:256 O-GlcNAc 249:256 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 1 4 theme O-linked 214:221 arg1 modification 293:304 a generalized post-translational modification 260:304 a generalized post-translational modification 260:304 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 1 4 theme O-linked 214:221 arg1 N-acetyl-β-D-glucosamine 223:246 intracerebral O-linked N-acetyl-β-D-glucosamine 200:246 intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) 200:257 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 8 5 theme hippocampal 1460:1470 arg1 modification 1481:1492 hippocampal O-GlcNAc modification 1460:1492 hippocampal O-GlcNAc modification of CUMS mice following LW administration 1460:1533 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 10 6 theme therapeutic 1829:1839 arg1 agent 1841:1845 a potential prophylactic and therapeutic agent 1800:1845 a potential prophylactic and therapeutic agent for chronic stress 1800:1864 LW therefore could be considered a potential prophylactic and therapeutic agent for chronic stress. 37152609 5 7 theme genera 951:956 arg1 abundance 958:966 genera abundance 951:966 genera abundance 951:966 Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. 37152609 9 8 theme CUMS 1756:1759 arg1 mice 1761:1764 CUMS mice 1756:1764 CUMS mice 1756:1764 In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. 37152609 8 9 theme CUMS 1497:1500 arg1 mice 1502:1505 CUMS mice 1497:1505 CUMS mice following LW administration 1497:1533 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 4 10 theme anxiety- 758:765 arg1 behaviors 787:795 anxiety- and depression-like behaviors 758:795 anxiety- and depression-like behaviors 758:795 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 1 11 theme substantial 152:162 arg1 body 164:167 A substantial body 150:167 A substantial body of evidence 150:179 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 10 12 dep potential 1802:1810 arg1 prophylactic 1812:1823 prophylactic 1812:1823 prophylactic 1812:1823 LW therefore could be considered a potential prophylactic and therapeutic agent for chronic stress. 37152609 2 13 theme mouse 557:561 arg1 models 563:568 stress mouse models 550:568 stress mouse models 550:568 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 7 14 theme CUMS 1362:1365 arg1 mice 1367:1370 CUMS mice 1362:1370 CUMS mice 1362:1370 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 0 15 theme cognitive 72:80 arg1 impairments 82:92 chronic stress-induced emotional and cognitive impairments 35:92 chronic stress-induced emotional and cognitive impairments in mice 35:100 Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification. 37152609 1 16 theme cognitive 378:386 arg1 impairments 388:398 stress-induced emotional and cognitive impairments 349:398 stress-induced emotional and cognitive impairments 349:398 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 3 17 theme O-GlcNAc 651:658 arg1 levels 660:665 intracerebral O-GlcNAc levels 637:665 intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice 637:714 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 4 18 theme behavioral 729:738 arg1 tests 740:744 The dynamic behavioral tests 717:744 The dynamic behavioral tests 717:744 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 4 19 theme recognition 808:818 arg1 memory 820:825 object recognition memory 801:825 object recognition memory of CUMS mice 801:838 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 7 20 theme Uridine 1214:1220 arg1 biosynthesis 1267:1278 the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis 1210:1278 the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process 1210:1286 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 5 21 theme study 1026:1030 arg1 groups 1032:1037 the study groups 1022:1037 the study groups 1022:1037 Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. 37152609 6 22 theme microbiota 1104:1113 arg1 abundance 1081:1089 the relative abundance 1068:1089 the relative abundance of these gut microbiota in CUMS mice 1068:1126 LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. 37152609 4 23 theme depression-like 771:785 arg1 behaviors 787:795 anxiety- and depression-like behaviors 758:795 anxiety- and depression-like behaviors 758:795 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 2 24 theme Liuwei 438:443 arg1 LW 462:463 LW 462:463 LW 462:463 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 2 24 theme Liuwei 438:443 arg1 formula 453:459 the Liuwei Dihuang formula 434:459 the Liuwei Dihuang formula (LW) 434:464 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 0 25 theme Liuwei 0:5 arg1 formula 15:21 Liuwei Dihuang formula 0:21 Liuwei Dihuang formula 0:21 Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification. 37152609 5 26 theme significant 979:989 arg1 difference 991:1000 a significant difference 977:1000 a significant difference in microbiome among the study groups 977:1037 Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. 37152609 10 27 theme chronic 1851:1857 arg1 stress 1859:1864 chronic stress 1851:1864 chronic stress 1851:1864 LW therefore could be considered a potential prophylactic and therapeutic agent for chronic stress. 37152609 5 28 dep analysis 931:938 arg1 discriminate 918:929 discriminate 918:929 discriminate 918:929 Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. 37152609 1 29 theme effective 326:334 arg1 regulator 336:344 an effective regulator 323:344 an effective regulator of stress-induced emotional and cognitive impairments 323:398 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 7 30 theme transferase 1341:1351 arg1 abundance 1297:1305 the abundance 1293:1305 the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice 1293:1370 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 2 31 theme various 533:539 arg1 types 541:545 various types 533:545 various types of stress mouse models 533:568 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 8 32 theme OGA 1572:1574 arg1 levels 1562:1567 the levels 1558:1567 the levels of OGA and OGT 1558:1582 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 3 33 theme stress 697:702 arg1 mice 711:714 chronic unpredictable mild stress (CUMS) mice 670:714 chronic unpredictable mild stress (CUMS) mice 670:714 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 0 34 theme chronic 35:41 arg1 impairments 82:92 chronic stress-induced emotional and cognitive impairments 35:92 chronic stress-induced emotional and cognitive impairments in mice 35:100 Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification. 37152609 9 35 theme LW 1597:1598 arg1 intervention 1600:1611 LW intervention 1597:1611 LW intervention 1597:1611 In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. 37152609 8 36 theme OGT 1580:1582 arg1 levels 1562:1567 the levels 1558:1567 the levels of OGA and OGT 1558:1582 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 3 37 theme unpredictable 678:690 arg1 CUMS 705:708 CUMS 705:708 CUMS 705:708 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 3 37 theme unpredictable 678:690 arg1 stress 697:702 chronic unpredictable mild stress 670:702 chronic unpredictable mild stress (CUMS) mice 670:714 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 0 38 theme emotional 58:66 arg1 impairments 82:92 chronic stress-induced emotional and cognitive impairments 35:92 chronic stress-induced emotional and cognitive impairments in mice 35:100 Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification. 37152609 1 39 theme emotional 364:372 arg1 impairments 388:398 stress-induced emotional and cognitive impairments 349:398 stress-induced emotional and cognitive impairments 349:398 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 6 40 theme control 1151:1157 arg1 levels 1165:1170 control mouse levels 1151:1170 control mouse levels 1151:1170 LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. 37152609 8 41 theme advantageous 1436:1447 arg1 changes 1449:1455 advantageous changes 1436:1455 advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration 1436:1533 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 7 42 theme O-GlcNAcase 1310:1320 arg1 abundance 1297:1305 the abundance 1293:1305 the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice 1293:1370 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 1 43 theme generalized 262:272 arg1 N-acetyl-β-D-glucosamine 223:246 intracerebral O-linked N-acetyl-β-D-glucosamine 200:246 intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) 200:257 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 1 43 theme generalized 262:272 arg1 modification 293:304 a generalized post-translational modification 260:304 a generalized post-translational modification 260:304 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 9 44 theme hippocampal 1637:1647 arg1 modification 1658:1669 hippocampal O-GlcNAc modification 1637:1669 hippocampal O-GlcNAc modification 1637:1669 In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. 37152609 2 45 dep Liuwei 438:443 arg1 Dihuang 445:451 Dihuang 445:451 Dihuang 445:451 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 9 46 theme modification 1658:1669 arg1 levels 1627:1632 the levels 1623:1632 the levels of hippocampal O-GlcNAc modification 1623:1669 In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. 37152609 6 47 theme CUMS 1118:1121 arg1 mice 1123:1126 CUMS mice 1118:1126 CUMS mice 1118:1126 LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. 37152609 8 48 mod modification 1481:1492 arg1 mice 1502:1505 CUMS mice 1497:1505 CUMS mice following LW administration 1497:1533 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 8 48 mod modification 1481:1492 arg3 O-GlcNAc 1472:1479 hippocampal O-GlcNAc modification 1460:1492 hippocampal O-GlcNAc modification of CUMS mice following LW administration 1460:1533 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 3 49 theme current 578:584 arg1 study 586:590 the current study 574:590 the current study 574:590 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 5 50 theme linear 911:916 arg1 LEfSe 941:945 LEfSe 941:945 LEfSe 941:945 Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. 37152609 5 50 theme linear 911:916 arg1 analysis 931:938 linear discriminate analysis 911:938 linear discriminate analysis (LEfSe) of genera abundance 911:966 Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. 37152609 9 51 theme emotional 1691:1699 arg1 impairments 1715:1725 the emotional and cognitive impairments 1687:1725 the emotional and cognitive impairments induced by chronic stress in CUMS mice 1687:1764 In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. 37152609 10 52 theme potential 1802:1810 arg1 agent 1841:1845 a potential prophylactic and therapeutic agent 1800:1845 a potential prophylactic and therapeutic agent for chronic stress 1800:1864 LW therefore could be considered a potential prophylactic and therapeutic agent for chronic stress. 37152609 1 53 theme intracerebral 200:212 arg1 O-GlcNAc 249:256 O-GlcNAc 249:256 O-GlcNAc 249:256 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 1 53 theme intracerebral 200:212 arg1 modification 293:304 a generalized post-translational modification 260:304 a generalized post-translational modification 260:304 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 1 53 theme intracerebral 200:212 arg1 N-acetyl-β-D-glucosamine 223:246 intracerebral O-linked N-acetyl-β-D-glucosamine 200:246 intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) 200:257 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 9 54 theme cognitive 1705:1713 arg1 impairments 1715:1725 the emotional and cognitive impairments 1687:1725 the emotional and cognitive impairments induced by chronic stress in CUMS mice 1687:1764 In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. 37152609 6 55 from abundance 1081:1089 arg1 mice 1123:1126 CUMS mice 1118:1126 CUMS mice 1118:1126 LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. 37152609 8 56 from changes 1449:1455 arg1 modification 1481:1492 hippocampal O-GlcNAc modification 1460:1492 hippocampal O-GlcNAc modification of CUMS mice following LW administration 1460:1533 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 8 56 from changes 1449:1455 arg1 levels 1562:1567 the levels 1558:1567 the levels of OGA and OGT 1558:1582 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 8 57 theme O-GlcNAc 1472:1479 arg1 modification 1481:1492 hippocampal O-GlcNAc modification 1460:1492 hippocampal O-GlcNAc modification of CUMS mice following LW administration 1460:1533 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 3 58 theme LW 631:632 arg1 effects 620:626 the effects 616:626 the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice 616:714 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 9 59 theme chronic 1738:1744 arg1 stress 1746:1751 chronic stress 1738:1751 chronic stress in CUMS mice 1738:1764 In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. 37152609 0 60 from impairments 82:92 arg1 mice 97:100 mice 97:100 mice 97:100 Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification. 37152609 7 61 theme PICRUSt 1398:1404 arg1 analysis 1406:1413 PICRUSt analysis 1398:1413 PICRUSt analysis 1398:1413 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 8 62 theme mice 1502:1505 arg1 modification 1481:1492 hippocampal O-GlcNAc modification 1460:1492 hippocampal O-GlcNAc modification of CUMS mice following LW administration 1460:1533 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 4 63 theme mice 835:838 arg1 behaviors 787:795 anxiety- and depression-like behaviors 758:795 anxiety- and depression-like behaviors 758:795 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 4 63 theme mice 835:838 arg1 memory 820:825 object recognition memory 801:825 object recognition memory of CUMS mice 801:838 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 5 64 theme abundance 958:966 arg1 LEfSe 941:945 LEfSe 941:945 LEfSe 941:945 Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. 37152609 5 64 theme abundance 958:966 arg1 analysis 931:938 linear discriminate analysis 911:938 linear discriminate analysis (LEfSe) of genera abundance 911:966 Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. 37152609 8 65 theme LW 1517:1518 arg1 administration 1520:1533 LW administration 1517:1533 LW administration 1517:1533 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 7 66 theme biosynthesis 1267:1278 arg1 process 1280:1286 the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process 1210:1286 the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process 1210:1286 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 3 67 theme intracerebral 637:649 arg1 levels 660:665 intracerebral O-GlcNAc levels 637:665 intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice 637:714 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 6 68 theme great 1052:1056 arg1 impact 1058:1063 a great impact 1050:1063 a great impact 1050:1063 LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. 37152609 2 69 theme stress 550:555 arg1 models 563:568 stress mouse models 550:568 stress mouse models 550:568 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 7 70 theme UDP-GlcNAc 1255:1264 arg1 biosynthesis 1267:1278 the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis 1210:1278 the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process 1210:1286 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 1 71 theme impairments 388:398 arg1 regulator 336:344 an effective regulator 323:344 an effective regulator of stress-induced emotional and cognitive impairments 323:398 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 1 72 theme evidence 172:179 arg1 body 164:167 A substantial body 150:167 A substantial body of evidence 150:179 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 4 73 theme dynamic 721:727 arg1 tests 740:744 The dynamic behavioral tests 717:744 The dynamic behavioral tests 717:744 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 7 74 theme diphosphate-N-acetylglucosamine 1222:1252 arg1 biosynthesis 1267:1278 the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis 1210:1278 the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process 1210:1286 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 9 75 from stress 1746:1751 arg1 mice 1761:1764 CUMS mice 1756:1764 CUMS mice 1756:1764 In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. 37152609 2 76 from dysfunctions 517:528 arg1 types 541:545 various types 533:545 various types of stress mouse models 533:568 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 4 77 theme object 801:806 arg1 memory 820:825 object recognition memory 801:825 object recognition memory of CUMS mice 801:838 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 0 78 theme O-GlcNAc 127:134 arg1 modification 136:147 hippocampal O-GlcNAc modification 115:147 hippocampal O-GlcNAc modification 115:147 Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification. 37152609 2 79 theme models 563:568 arg1 types 541:545 various types 533:545 various types of stress mouse models 533:568 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 1 80 link O-linked 214:221 arg1 O-GlcNAc 249:256 O-GlcNAc 249:256 O-GlcNAc 249:256 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 1 80 link O-linked 214:221 arg1 modification 293:304 a generalized post-translational modification 260:304 a generalized post-translational modification 260:304 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 1 80 link O-linked 214:221 arg1 N-acetyl-β-D-glucosamine 223:246 intracerebral O-linked N-acetyl-β-D-glucosamine 200:246 intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) 200:257 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 3 81 from levels 660:665 arg1 mice 711:714 chronic unpredictable mild stress (CUMS) mice 670:714 chronic unpredictable mild stress (CUMS) mice 670:714 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 0 82 theme Dihuang 7:13 arg1 formula 15:21 Liuwei Dihuang formula 0:21 Liuwei Dihuang formula 0:21 Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification. 37152609 6 83 theme gut 1100:1102 arg1 microbiota 1104:1113 these gut microbiota 1094:1113 these gut microbiota 1094:1113 LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. 37152609 2 84 theme emotional 493:501 arg1 dysfunctions 517:528 the emotional and cognitive dysfunctions 489:528 the emotional and cognitive dysfunctions in various types of stress mouse models 489:568 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 3 85 from effects 620:626 arg1 levels 660:665 intracerebral O-GlcNAc levels 637:665 intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice 637:714 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 7 86 theme O-GlcNAc 1332:1339 arg1 OGT 1354:1356 OGT 1354:1356 OGT 1354:1356 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 7 86 theme O-GlcNAc 1332:1339 arg1 transferase 1341:1351 O-GlcNAc transferase 1332:1351 O-GlcNAc transferase (OGT) 1332:1357 We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. 37152609 3 87 theme mild 692:695 arg1 CUMS 705:708 CUMS 705:708 CUMS 705:708 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 3 87 theme mild 692:695 arg1 stress 697:702 chronic unpredictable mild stress 670:702 chronic unpredictable mild stress (CUMS) mice 670:714 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 0 88 theme stress-induced 43:56 arg1 impairments 82:92 chronic stress-induced emotional and cognitive impairments 35:92 chronic stress-induced emotional and cognitive impairments in mice 35:100 Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification. 37152609 6 89 theme relative 1072:1079 arg1 abundance 1081:1089 the relative abundance 1068:1089 the relative abundance of these gut microbiota in CUMS mice 1068:1126 LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. 37152609 3 90 theme chronic 670:676 arg1 CUMS 705:708 CUMS 705:708 CUMS 705:708 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 3 90 theme chronic 670:676 arg1 stress 697:702 chronic unpredictable mild stress 670:702 chronic unpredictable mild stress (CUMS) mice 670:714 In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. 37152609 0 91 theme hippocampal 115:125 arg1 modification 136:147 hippocampal O-GlcNAc modification 115:147 hippocampal O-GlcNAc modification 115:147 Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification. 37152609 8 92 from changes 1547:1553 arg1 modification 1481:1492 hippocampal O-GlcNAc modification 1460:1492 hippocampal O-GlcNAc modification of CUMS mice following LW administration 1460:1533 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 8 92 from changes 1547:1553 arg1 levels 1562:1567 the levels 1558:1567 the levels of OGA and OGT 1558:1582 We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. 37152609 1 93 theme stress-induced 349:362 arg1 impairments 388:398 stress-induced emotional and cognitive impairments 349:398 stress-induced emotional and cognitive impairments 349:398 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 6 94 theme mouse 1159:1163 arg1 levels 1165:1170 control mouse levels 1151:1170 control mouse levels 1151:1170 LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. 37152609 2 95 theme cognitive 507:515 arg1 dysfunctions 517:528 the emotional and cognitive dysfunctions 489:528 the emotional and cognitive dysfunctions in various types of stress mouse models 489:568 Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. 37152609 4 96 theme dose-dependent 859:872 arg1 manner 874:879 a dose-dependent manner 857:879 a dose-dependent manner 857:879 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 5 97 from difference 991:1000 arg1 microbiome 1005:1014 microbiome 1005:1014 microbiome 1005:1014 Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. 37152609 4 98 theme CUMS 830:833 arg1 mice 835:838 CUMS mice 830:838 CUMS mice 830:838 The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. 37152609 1 99 theme post-translational 274:291 arg1 N-acetyl-β-D-glucosamine 223:246 intracerebral O-linked N-acetyl-β-D-glucosamine 200:246 intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) 200:257 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 37152609 1 99 theme post-translational 274:291 arg1 modification 293:304 a generalized post-translational modification 260:304 a generalized post-translational modification 260:304 A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. 36398863 0 0 theme Hypoxic 84:90 arg1 Therapy 98:104 Efficient Hypoxic Tumor Therapy 74:104 Efficient Hypoxic Tumor Therapy 74:104 Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy. 36398863 4 1 with porphyrin 752:760 arg1 chains 790:795 O-linked cationic side chains 767:795 O-linked cationic side chains 767:795 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 2 2 theme low 354:356 arg1 tolerance 358:366 a low tolerance 352:366 a low tolerance for a hypoxic condition 352:390 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 1 3 theme cancers 247:253 arg1 PDT 239:241 PDT 239:241 PDT 239:241 As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. 36398863 1 3 theme cancers 247:253 arg1 therapy 230:236 the photodynamic therapy 213:236 the photodynamic therapy (PDT) of cancers 213:253 As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. 36398863 0 4 theme Efficient 74:82 arg1 Therapy 98:104 Efficient Hypoxic Tumor Therapy 74:104 Efficient Hypoxic Tumor Therapy 74:104 Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy. 36398863 4 5 link O-linked 767:774 arg1 chains 790:795 O-linked cationic side chains 767:795 O-linked cationic side chains 767:795 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 8 6 theme porphyrin 1392:1400 arg1 property 1380:1387 the photodynamic property 1363:1387 the photodynamic property of porphyrin 1363:1400 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 8 7 from power 1323:1327 arg1 tuning 1356:1361 tuning 1356:1361 tuning 1356:1361 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 8 8 theme photodynamic 1367:1378 arg1 property 1380:1387 the photodynamic property 1363:1387 the photodynamic property of porphyrin 1363:1400 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 2 9 from self-quenching 314:327 arg1 generation 336:345 ROS generation 332:345 ROS generation 332:345 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 0 10 theme Tumor 92:96 arg1 Therapy 98:104 Efficient Hypoxic Tumor Therapy 74:104 Efficient Hypoxic Tumor Therapy 74:104 Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy. 36398863 3 11 theme hypoxic 566:572 arg1 tumors 574:579 hypoxic tumors 566:579 hypoxic tumors 566:579 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 3 11 theme hypoxic 566:572 arg1 combination 592:602 combination 592:602 combination with additional active components or therapies 592:649 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 7 12 theme effective 1258:1266 arg1 capability 1283:1292 highly effective tumor ablation capability 1251:1292 highly effective tumor ablation capability 1251:1292 Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. 36398863 2 13 theme water 276:280 arg1 solubility 282:291 their poor water solubility 265:291 their poor water solubility 265:291 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 6 14 theme IC50 1143:1146 arg1 values 1148:1153 low IC50 values 1139:1153 low IC50 values 1139:1153 The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. 36398863 4 15 from generation 888:897 arg1 pathways 948:955 type-II photodynamic pathways 927:955 type-II photodynamic pathways 927:955 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 4 15 from generation 888:897 arg1 type-I 916:921 type-I 916:921 type-I 916:921 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 4 16 theme ROS 884:886 arg1 generation 888:897 significantly enhanced ROS generation 861:897 significantly enhanced ROS generation 861:897 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 6 17 theme cationic 1078:1085 arg1 porphyrin 1087:1095 The cationic porphyrin 1074:1095 The cationic porphyrin 1074:1095 The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. 36398863 2 18 theme poor 271:274 arg1 solubility 282:291 their poor water solubility 265:291 their poor water solubility 265:291 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 4 19 dep solubility 824:833 arg1 efficacy 899:906 efficacy 899:906 efficacy 899:906 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 7 20 theme PDT 1207:1209 arg1 study 1211:1215 in vivo PDT study 1199:1215 in vivo PDT study 1199:1215 Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. 36398863 8 21 theme chemistry 1343:1351 arg1 power 1323:1327 the power 1319:1327 the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics 1319:1565 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 4 22 theme enhanced 875:882 arg1 generation 888:897 significantly enhanced ROS generation 861:897 significantly enhanced ROS generation 861:897 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 8 23 from therapy 1548:1554 arg1 clinics 1559:1565 clinics 1559:1565 clinics 1559:1565 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 6 24 theme PDT 1121:1123 arg1 efficacy 1125:1132 high in vitro PDT efficacy 1107:1132 high in vitro PDT efficacy 1107:1132 The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. 36398863 6 25 theme in 1112:1113 arg1 efficacy 1125:1132 high in vitro PDT efficacy 1107:1132 high in vitro PDT efficacy 1107:1132 The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. 36398863 7 26 theme cationic 1222:1229 arg1 porphyrin 1231:1239 the cationic porphyrin 1218:1239 the cationic porphyrin 1218:1239 Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. 36398863 7 27 theme tumor 1268:1272 arg1 capability 1283:1292 highly effective tumor ablation capability 1251:1292 highly effective tumor ablation capability 1251:1292 Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. 36398863 4 28 theme cationic 776:783 arg1 chains 790:795 O-linked cationic side chains 767:795 O-linked cationic side chains 767:795 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 2 29 theme hypoxic 374:380 arg1 condition 382:390 a hypoxic condition 372:390 a hypoxic condition 372:390 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 7 30 theme in 1199:1200 arg1 study 1211:1215 in vivo PDT study 1199:1215 in vivo PDT study 1199:1215 Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. 36398863 8 31 theme increasing 1518:1527 arg1 demands 1529:1535 the increasing demands 1514:1535 the increasing demands for cancer therapy in clinics 1514:1565 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 4 32 theme O-linked 767:774 arg1 chains 790:795 O-linked cationic side chains 767:795 O-linked cationic side chains 767:795 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 0 33 theme Type-II 20:26 arg1 Production 32:41 Type-II ROS Production 20:41 Type-II ROS Production 20:41 Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy. 36398863 8 34 theme anticancer 1456:1465 arg1 performance 1467:1477 the anticancer performance 1452:1477 the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics 1452:1565 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 2 35 from tolerance 358:366 arg1 generation 336:345 ROS generation 332:345 ROS generation 332:345 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 2 36 theme aggregation-induced 294:312 arg1 self-quenching 314:327 aggregation-induced self-quenching 294:327 aggregation-induced self-quenching on ROS generation 294:345 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 8 37 theme new 1418:1420 arg1 strategy 1432:1439 a new effective strategy 1416:1439 a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics 1416:1565 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 2 38 theme therapeutic 422:432 arg1 outcomes 434:441 unsatisfied therapeutic outcomes 410:441 unsatisfied therapeutic outcomes 410:441 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 3 39 with combination 592:602 arg1 therapies 641:649 therapies 641:649 therapies 641:649 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 3 39 with combination 592:602 arg1 components 627:636 additional active components 609:636 additional active components 609:636 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 8 40 dep tuning 1356:1361 arg1 property 1380:1387 the photodynamic property 1363:1387 the photodynamic property of porphyrin 1363:1400 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 3 41 theme photosensitizers 537:552 arg1 efficacy 510:517 the PDT efficacy 502:517 the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process 502:709 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 4 42 theme side 785:788 arg1 chains 790:795 O-linked cationic side chains 767:795 O-linked cationic side chains 767:795 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 2 43 theme unsatisfied 410:420 arg1 outcomes 434:441 unsatisfied therapeutic outcomes 410:441 unsatisfied therapeutic outcomes 410:441 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 3 44 theme PDT 506:508 arg1 efficacy 510:517 the PDT efficacy 502:517 the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process 502:709 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 3 45 theme great 455:459 arg1 efforts 461:467 great efforts 455:467 great efforts 455:467 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 3 46 theme active 620:625 arg1 components 627:636 additional active components 609:636 additional active components 609:636 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 1 47 theme photodynamic 217:228 arg1 PDT 239:241 PDT 239:241 PDT 239:241 As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. 36398863 1 47 theme photodynamic 217:228 arg1 therapy 230:236 the photodynamic therapy 213:236 the photodynamic therapy (PDT) of cancers 213:253 As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. 36398863 0 48 theme ROS 28:30 arg1 Production 32:41 Type-II ROS Production 20:41 Type-II ROS Production 20:41 Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy. 36398863 8 49 theme side-chain 1332:1341 arg1 chemistry 1343:1351 side-chain chemistry 1332:1351 side-chain chemistry 1332:1351 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 6 50 theme high 1107:1110 arg1 efficacy 1125:1132 high in vitro PDT efficacy 1107:1132 high in vitro PDT efficacy 1107:1132 The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. 36398863 0 51 theme Water-Soluble 46:58 arg1 Porphyrin 60:68 Water-Soluble Porphyrin 46:68 Water-Soluble Porphyrin 46:68 Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy. 36398863 4 52 theme photodynamic 935:946 arg1 pathways 948:955 type-II photodynamic pathways 927:955 type-II photodynamic pathways 927:955 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 8 53 theme photosensitizers 1482:1497 arg1 performance 1467:1477 the anticancer performance 1452:1477 the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics 1452:1565 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 5 54 theme side 1001:1004 arg1 chains 1006:1011 side chains 1001:1011 side chains 1001:1011 We have also found that the end charges of side chains can dramatically affect the ROS generation of the porphyrin. 36398863 6 55 theme low 1139:1141 arg1 values 1148:1153 low IC50 values 1139:1153 low IC50 values 1139:1153 The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. 36398863 4 56 theme water-soluble 738:750 arg1 porphyrin 752:760 a novel water-soluble porphyrin 730:760 a novel water-soluble porphyrin 730:760 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 4 57 theme type-II 927:933 arg1 pathways 948:955 type-II photodynamic pathways 927:955 type-II photodynamic pathways 927:955 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 5 58 theme porphyrin 1063:1071 arg1 generation 1045:1054 the ROS generation 1037:1054 the ROS generation of the porphyrin 1037:1071 We have also found that the end charges of side chains can dramatically affect the ROS generation of the porphyrin. 36398863 3 59 theme additional 609:618 arg1 components 627:636 additional active components 609:636 additional active components 609:636 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 4 60 theme novel 732:736 arg1 porphyrin 752:760 a novel water-soluble porphyrin 730:760 a novel water-soluble porphyrin 730:760 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 7 61 theme ablation 1274:1281 arg1 capability 1283:1292 highly effective tumor ablation capability 1251:1292 highly effective tumor ablation capability 1251:1292 Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. 36398863 7 62 dep in 1199:1200 arg1 vivo 1202:1205 vivo 1202:1205 vivo 1202:1205 Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. 36398863 6 63 dep values 1148:1153 arg1 both 1155:1158 both 1155:1158 both 1155:1158 The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. 36398863 4 64 from photostability 841:854 arg1 pathways 948:955 type-II photodynamic pathways 927:955 type-II photodynamic pathways 927:955 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 4 64 from photostability 841:854 arg1 type-I 916:921 type-I 916:921 type-I 916:921 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 1 65 theme successful 119:128 arg1 photosensitizers 150:165 the most successful clinically approved photosensitizers 110:165 the most successful clinically approved photosensitizers 110:165 As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. 36398863 1 65 theme successful 119:128 arg1 porphyrins 168:177 porphyrins 168:177 porphyrins 168:177 As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. 36398863 5 66 theme end 986:988 arg1 charges 990:996 the end charges 982:996 the end charges of side chains 982:1011 We have also found that the end charges of side chains can dramatically affect the ROS generation of the porphyrin. 36398863 6 67 dep in 1112:1113 arg1 vitro 1115:1119 vitro 1115:1119 vitro 1115:1119 The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. 36398863 4 68 theme good 813:816 arg1 solubility 824:833 good water solubility 813:833 good water solubility 813:833 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 3 69 theme therapeutic 691:701 arg1 process 703:709 the therapeutic process 687:709 the therapeutic process 687:709 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 4 70 theme water 818:822 arg1 solubility 824:833 good water solubility 813:833 good water solubility 813:833 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 2 71 theme ROS 332:334 arg1 generation 336:345 ROS generation 332:345 ROS generation 332:345 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 2 72 from solubility 282:291 arg1 generation 336:345 ROS generation 332:345 ROS generation 332:345 However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. 36398863 5 73 theme chains 1006:1011 arg1 charges 990:996 the end charges 982:996 the end charges of side chains 982:1011 We have also found that the end charges of side chains can dramatically affect the ROS generation of the porphyrin. 36398863 4 74 theme high 836:839 arg1 photostability 841:854 high photostability 836:854 high photostability 836:854 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 1 75 theme approved 141:148 arg1 photosensitizers 150:165 the most successful clinically approved photosensitizers 110:165 the most successful clinically approved photosensitizers 110:165 As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. 36398863 1 75 theme approved 141:148 arg1 porphyrins 168:177 porphyrins 168:177 porphyrins 168:177 As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. 36398863 0 76 theme Porphyrin 60:68 arg1 Production 32:41 Type-II ROS Production 20:41 Type-II ROS Production 20:41 Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy. 36398863 0 76 theme Porphyrin 60:68 arg1 Type-I 9:14 Type-I 9:14 Type-I 9:14 Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy. 36398863 8 77 theme cancer 1541:1546 arg1 therapy 1548:1554 cancer therapy 1541:1554 cancer therapy in clinics 1541:1565 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36398863 5 78 theme ROS 1041:1043 arg1 generation 1045:1054 the ROS generation 1037:1054 the ROS generation of the porphyrin 1037:1071 We have also found that the end charges of side chains can dramatically affect the ROS generation of the porphyrin. 36398863 4 79 from solubility 824:833 arg1 pathways 948:955 type-II photodynamic pathways 927:955 type-II photodynamic pathways 927:955 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 4 79 from solubility 824:833 arg1 type-I 916:921 type-I 916:921 type-I 916:921 Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. 36398863 3 80 theme porphyrin-type 522:535 arg1 photosensitizers 537:552 porphyrin-type photosensitizers 522:552 porphyrin-type photosensitizers 522:552 Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. 36398863 8 81 theme effective 1422:1430 arg1 strategy 1432:1439 a new effective strategy 1416:1439 a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics 1416:1565 This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics. 36256656 9 0 theme genetic 1596:1602 arg1 cluster 1567:1573 the MUC3 cluster 1558:1573 the MUC3 cluster which is a conserved genetic unit in vertebrates 1558:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 9 0 theme genetic 1596:1602 arg1 unit 1604:1607 a conserved genetic unit 1584:1607 a conserved genetic unit in vertebrates 1584:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 2 1 theme distinct 350:357 arg1 group 359:363 a distinct group 348:363 a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment 348:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 2 1 theme distinct 350:357 arg1 mucins 337:342 Membrane mucins 328:342 Membrane mucins 328:342 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 2 1 theme distinct 350:357 arg1 mucins 368:373 mucins 368:373 mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment 368:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 10 2 theme disease-associated 1697:1714 arg1 polymorphisms 1716:1728 disease-associated polymorphisms 1697:1728 disease-associated polymorphisms 1697:1728 We anticipate our results to be the starting point for the detection of disease-associated polymorphisms in the human MUC3 cluster. 36256656 8 3 from MUC3A 1402:1406 arg1 cluster 1451:1457 the human MUC3 cluster 1436:1457 the human MUC3 cluster 1436:1457 Furthermore, we show that MUC3A, MUC3B, MUC12, and MUC17 in the human MUC3 cluster are expressed in intestinal epithelial cells (IECs). 36256656 1 4 theme selective 251:259 arg1 barriers 273:280 selective biochemical barriers 251:280 selective biochemical barriers against harmful microorganisms and molecules 251:325 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 1 5 theme Human 94:98 arg1 surfaces 107:114 Human tissue surfaces 94:114 Human tissue surfaces 94:114 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 4 6 theme mucin 677:681 arg1 domains 683:689 mucin domains 677:689 mucin domains 677:689 However, the repetitive nature of mucin domains makes them prone to recombination and renders their genetic sequences particularly difficult to read with standard sequencing technologies. 36256656 6 7 theme mucin 1172:1176 arg1 genes 1178:1182 four structurally related membrane mucin genes 1137:1182 four structurally related membrane mucin genes that we name the MUC3 cluster 1137:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 3 8 theme O-linked 590:597 arg1 glycosylation 599:611 extensive O-linked glycosylation 580:611 extensive O-linked glycosylation 580:611 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 8 9 from MUC12 1416:1420 arg1 cluster 1451:1457 the human MUC3 cluster 1436:1457 the human MUC3 cluster 1436:1457 Furthermore, we show that MUC3A, MUC3B, MUC12, and MUC17 in the human MUC3 cluster are expressed in intestinal epithelial cells (IECs). 36256656 1 10 theme macromolecular 152:165 arg1 proteins 179:186 macromolecular sugar-laden proteins 152:186 macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules 152:325 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 6 11 theme related 1155:1161 arg1 genes 1178:1182 four structurally related membrane mucin genes 1137:1182 four structurally related membrane mucin genes that we name the MUC3 cluster 1137:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 1 12 theme diverse 196:202 arg1 functions 204:212 diverse functions 196:212 diverse functions 196:212 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 10 13 theme starting 1661:1668 arg1 point 1670:1674 the starting point 1657:1674 the starting point for the detection of disease-associated polymorphisms in the human MUC3 cluster 1657:1754 We anticipate our results to be the starting point for the detection of disease-associated polymorphisms in the human MUC3 cluster. 36256656 10 13 theme starting 1661:1668 arg1 results 1643:1649 our results 1639:1649 our results 1639:1649 We anticipate our results to be the starting point for the detection of disease-associated polymorphisms in the human MUC3 cluster. 36256656 8 14 from MUC3B 1409:1413 arg1 cluster 1451:1457 the human MUC3 cluster 1436:1457 the human MUC3 cluster 1436:1457 Furthermore, we show that MUC3A, MUC3B, MUC12, and MUC17 in the human MUC3 cluster are expressed in intestinal epithelial cells (IECs). 36256656 1 15 theme proteins 179:186 arg1 mucins 132:137 mucins 132:137 mucins 132:137 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 1 15 theme proteins 179:186 arg1 family 142:147 a family 140:147 a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules 140:325 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 5 16 theme function 945:952 arg1 investigation 923:935 the investigation 919:935 the investigation of gene function in health and disease 919:974 As a result, human mucin genes suffer from significant sequence gaps that have hampered the investigation of gene function in health and disease. 36256656 0 17 from cluster 63:69 arg1 chromosome 80:89 human chromosome 7 74:91 human chromosome 7 74:91 Discovery of a MUC3B gene reconstructs the membrane mucin gene cluster on human chromosome 7. 36256656 3 18 theme linear 621:626 arg1 domains 634:640 linear mucin domains 621:640 linear mucin domains 621:640 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 5 19 theme significant 874:884 arg1 gaps 895:898 significant sequence gaps 874:898 significant sequence gaps that have hampered the investigation of gene function in health and disease 874:974 As a result, human mucin genes suffer from significant sequence gaps that have hampered the investigation of gene function in health and disease. 36256656 11 20 theme intestinal 1899:1908 arg1 organoids 1910:1918 human intestinal organoids 1893:1918 human intestinal organoids 1893:1918 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 1 21 theme tissue 100:105 arg1 surfaces 107:114 Human tissue surfaces 94:114 Human tissue surfaces 94:114 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 9 22 from unit 1604:1607 arg1 vertebrates 1612:1622 vertebrates 1612:1622 vertebrates 1612:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 7 23 theme conserved 1345:1353 arg1 elements 1366:1373 evolutionarily conserved regulatory elements 1330:1373 evolutionarily conserved regulatory elements 1330:1373 We found that MUC3B shares high sequence identity with the known MUC3A gene and that the two genes are governed by evolutionarily conserved regulatory elements. 36256656 4 24 theme genetic 743:749 arg1 sequences 751:759 their genetic sequences 737:759 their genetic sequences 737:759 However, the repetitive nature of mucin domains makes them prone to recombination and renders their genetic sequences particularly difficult to read with standard sequencing technologies. 36256656 10 25 theme polymorphisms 1716:1728 arg1 detection 1684:1692 the detection 1680:1692 the detection of disease-associated polymorphisms in the human MUC3 cluster 1680:1754 We anticipate our results to be the starting point for the detection of disease-associated polymorphisms in the human MUC3 cluster. 36256656 8 26 theme MUC3 1446:1449 arg1 cluster 1451:1457 the human MUC3 cluster 1436:1457 the human MUC3 cluster 1436:1457 Furthermore, we show that MUC3A, MUC3B, MUC12, and MUC17 in the human MUC3 cluster are expressed in intestinal epithelial cells (IECs). 36256656 6 27 theme MUC3 1201:1204 arg1 cluster 1206:1212 the MUC3 cluster 1197:1212 the MUC3 cluster 1197:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 10 28 from detection 1684:1692 arg1 cluster 1748:1754 the human MUC3 cluster 1733:1754 the human MUC3 cluster 1733:1754 We anticipate our results to be the starting point for the detection of disease-associated polymorphisms in the human MUC3 cluster. 36256656 8 29 from MUC17 1427:1431 arg1 cluster 1451:1457 the human MUC3 cluster 1436:1457 the human MUC3 cluster 1436:1457 Furthermore, we show that MUC3A, MUC3B, MUC12, and MUC17 in the human MUC3 cluster are expressed in intestinal epithelial cells (IECs). 36256656 11 30 theme mouse 1932:1936 arg1 models 1938:1943 genetic mouse models 1924:1943 genetic mouse models 1924:1943 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 5 31 from investigation 923:935 arg1 disease 968:974 disease 968:974 disease 968:974 As a result, human mucin genes suffer from significant sequence gaps that have hampered the investigation of gene function in health and disease. 36256656 5 31 from investigation 923:935 arg1 health 957:962 health 957:962 health 957:962 As a result, human mucin genes suffer from significant sequence gaps that have hampered the investigation of gene function in health and disease. 36256656 0 32 theme human 74:78 arg1 chromosome 80:89 human chromosome 7 74:91 human chromosome 7 74:91 Discovery of a MUC3B gene reconstructs the membrane mucin gene cluster on human chromosome 7. 36256656 3 33 theme sequences 557:565 arg1 stretches 526:534 long stretches 521:534 long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains 521:640 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 6 34 theme human 1004:1008 arg1 assembly 1017:1024 a recent human genome assembly 995:1024 a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster 995:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 8 35 theme epithelial 1487:1496 arg1 cells 1498:1502 intestinal epithelial cells 1476:1502 intestinal epithelial cells (IECs) 1476:1509 Furthermore, we show that MUC3A, MUC3B, MUC12, and MUC17 in the human MUC3 cluster are expressed in intestinal epithelial cells (IECs). 36256656 8 35 theme epithelial 1487:1496 arg1 IECs 1505:1508 IECs 1505:1508 IECs 1505:1508 Furthermore, we show that MUC3A, MUC3B, MUC12, and MUC17 in the human MUC3 cluster are expressed in intestinal epithelial cells (IECs). 36256656 4 36 theme sequencing 806:815 arg1 technologies 817:828 standard sequencing technologies 797:828 standard sequencing technologies 797:828 However, the repetitive nature of mucin domains makes them prone to recombination and renders their genetic sequences particularly difficult to read with standard sequencing technologies. 36256656 2 37 theme dense 441:445 arg1 glycocalyx 447:456 a dense glycocalyx 439:456 a dense glycocalyx facing the extracellular environment 439:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 11 38 theme function 1841:1848 arg1 exploration 1804:1814 the exploration 1800:1814 the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models 1800:1943 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 1 39 theme biochemical 261:271 arg1 barriers 273:280 selective biochemical barriers 251:280 selective biochemical barriers against harmful microorganisms and molecules 251:325 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 9 40 theme existing 1533:1540 arg1 gaps 1550:1553 existing genetic gaps 1533:1553 existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates 1533:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 11 41 theme genetic 1924:1930 arg1 models 1938:1943 genetic mouse models 1924:1943 genetic mouse models 1924:1943 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 11 42 from exploration 1804:1814 arg1 organoids 1910:1918 human intestinal organoids 1893:1918 human intestinal organoids 1893:1918 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 11 42 from exploration 1804:1814 arg1 models 1878:1883 widely used experimental models 1853:1883 widely used experimental models such as human intestinal organoids and genetic mouse models 1853:1943 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 11 42 from exploration 1804:1814 arg1 models 1938:1943 genetic mouse models 1924:1943 genetic mouse models 1924:1943 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 5 43 theme mucin 850:854 arg1 genes 856:860 human mucin genes 844:860 human mucin genes 844:860 As a result, human mucin genes suffer from significant sequence gaps that have hampered the investigation of gene function in health and disease. 36256656 6 44 theme located 1075:1081 arg1 gene 1070:1073 a previously unmapped MUC3B gene 1042:1073 a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster 1042:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 2 45 theme extracellular 469:481 arg1 environment 483:493 the extracellular environment 465:493 the extracellular environment 465:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 11 46 theme experimental 1865:1876 arg1 organoids 1910:1918 human intestinal organoids 1893:1918 human intestinal organoids 1893:1918 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 11 46 theme experimental 1865:1876 arg1 models 1878:1883 widely used experimental models 1853:1883 widely used experimental models such as human intestinal organoids and genetic mouse models 1853:1943 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 11 46 theme experimental 1865:1876 arg1 models 1938:1943 genetic mouse models 1924:1943 genetic mouse models 1924:1943 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 2 47 theme cell 407:410 arg1 surfaces 412:419 epithelial cell surfaces 396:419 epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment 396:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 0 48 theme gene 21:24 arg1 Discovery 0:8 Discovery 0:8 Discovery of a MUC3B gene 0:24 Discovery of a MUC3B gene reconstructs the membrane mucin gene cluster on human chromosome 7. 36256656 6 49 theme MUC3B 1064:1068 arg1 gene 1070:1073 a previously unmapped MUC3B gene 1042:1073 a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster 1042:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 0 50 theme mucin 52:56 arg1 cluster 63:69 the membrane mucin gene cluster 39:69 the membrane mucin gene cluster on human chromosome 7 39:91 Discovery of a MUC3B gene reconstructs the membrane mucin gene cluster on human chromosome 7. 36256656 2 51 attach attached 384:391 arg2 mucins 368:373 mucins 368:373 mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment 368:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 2 51 attach attached 384:391 arg1 surfaces 412:419 epithelial cell surfaces 396:419 epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment 396:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 7 52 theme MUC3A 1280:1284 arg1 gene 1286:1289 the known MUC3A gene 1270:1289 the known MUC3A gene 1270:1289 We found that MUC3B shares high sequence identity with the known MUC3A gene and that the two genes are governed by evolutionarily conserved regulatory elements. 36256656 3 53 theme long 521:524 arg1 stretches 526:534 long stretches 521:534 long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains 521:640 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 9 54 theme conserved 1586:1594 arg1 cluster 1567:1573 the MUC3 cluster 1558:1573 the MUC3 cluster which is a conserved genetic unit in vertebrates 1558:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 9 54 theme conserved 1586:1594 arg1 unit 1604:1607 a conserved genetic unit 1584:1607 a conserved genetic unit in vertebrates 1584:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 7 55 theme high 1242:1245 arg1 identity 1256:1263 high sequence identity 1242:1263 high sequence identity 1242:1263 We found that MUC3B shares high sequence identity with the known MUC3A gene and that the two genes are governed by evolutionarily conserved regulatory elements. 36256656 3 56 theme repeated 548:555 arg1 sequences 557:565 tandemly repeated sequences 539:565 tandemly repeated sequences 539:565 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 3 57 theme extensive 580:588 arg1 glycosylation 599:611 extensive O-linked glycosylation 580:611 extensive O-linked glycosylation 580:611 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 6 58 from locus 1094:1098 arg1 located 1075:1081 located 1075:1081 located 1075:1081 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 6 58 from locus 1094:1098 arg1 chromosome 1103:1112 chromosome 7 1103:1114 chromosome 7 1103:1114 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 5 59 theme sequence 886:893 arg1 gaps 895:898 significant sequence gaps 874:898 significant sequence gaps that have hampered the investigation of gene function in health and disease 874:974 As a result, human mucin genes suffer from significant sequence gaps that have hampered the investigation of gene function in health and disease. 36256656 6 60 theme genes 1178:1182 arg1 cluster 1126:1132 a cluster 1124:1132 a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster 1124:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 10 61 theme MUC3 1743:1746 arg1 cluster 1748:1754 the human MUC3 cluster 1733:1754 the human MUC3 cluster 1733:1754 We anticipate our results to be the starting point for the detection of disease-associated polymorphisms in the human MUC3 cluster. 36256656 6 62 theme recent 997:1002 arg1 assembly 1017:1024 a recent human genome assembly 995:1024 a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster 995:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 6 63 theme membrane 1163:1170 arg1 genes 1178:1182 four structurally related membrane mucin genes 1137:1182 four structurally related membrane mucin genes that we name the MUC3 cluster 1137:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 4 64 theme domains 683:689 arg1 nature 667:672 the repetitive nature 652:672 the repetitive nature of mucin domains 652:689 However, the repetitive nature of mucin domains makes them prone to recombination and renders their genetic sequences particularly difficult to read with standard sequencing technologies. 36256656 1 65 theme sugar-laden 167:177 arg1 proteins 179:186 macromolecular sugar-laden proteins 152:186 macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules 152:325 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 10 66 theme human 1737:1741 arg1 cluster 1748:1754 the human MUC3 cluster 1733:1754 the human MUC3 cluster 1733:1754 We anticipate our results to be the starting point for the detection of disease-associated polymorphisms in the human MUC3 cluster. 36256656 3 67 gly glycosylation 599:611 arg1 stretches 526:534 long stretches 521:534 long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains 521:640 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 11 68 theme human 1893:1897 arg1 organoids 1910:1918 human intestinal organoids 1893:1918 human intestinal organoids 1893:1918 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 5 69 theme gene 940:943 arg1 function 945:952 gene function 940:952 gene function 940:952 As a result, human mucin genes suffer from significant sequence gaps that have hampered the investigation of gene function in health and disease. 36256656 8 70 theme human 1440:1444 arg1 cluster 1451:1457 the human MUC3 cluster 1436:1457 the human MUC3 cluster 1436:1457 Furthermore, we show that MUC3A, MUC3B, MUC12, and MUC17 in the human MUC3 cluster are expressed in intestinal epithelial cells (IECs). 36256656 9 71 from gaps 1550:1553 arg1 cluster 1567:1573 the MUC3 cluster 1558:1573 the MUC3 cluster which is a conserved genetic unit in vertebrates 1558:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 9 71 from gaps 1550:1553 arg1 unit 1604:1607 a conserved genetic unit 1584:1607 a conserved genetic unit in vertebrates 1584:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 6 72 theme unmapped 1055:1062 arg1 gene 1070:1073 a previously unmapped MUC3B gene 1042:1073 a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster 1042:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 7 73 theme regulatory 1355:1364 arg1 elements 1366:1373 evolutionarily conserved regulatory elements 1330:1373 evolutionarily conserved regulatory elements 1330:1373 We found that MUC3B shares high sequence identity with the known MUC3A gene and that the two genes are governed by evolutionarily conserved regulatory elements. 36256656 0 74 theme gene 58:61 arg1 cluster 63:69 the membrane mucin gene cluster 39:69 the membrane mucin gene cluster on human chromosome 7 39:91 Discovery of a MUC3B gene reconstructs the membrane mucin gene cluster on human chromosome 7. 36256656 3 75 theme mucin 628:632 arg1 domains 634:640 linear mucin domains 621:640 linear mucin domains 621:640 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 3 76 contain carry 515:519 arg2 stretches 526:534 long stretches 521:534 long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains 521:640 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 3 76 contain carry 515:519 arg1 proteins 506:513 All mucin proteins 496:513 All mucin proteins 496:513 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 11 77 theme intestinal 1819:1828 arg1 function 1841:1848 intestinal mucin gene function 1819:1848 intestinal mucin gene function 1819:1848 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 3 78 link O-linked 590:597 arg1 glycosylation 599:611 extensive O-linked glycosylation 580:611 extensive O-linked glycosylation 580:611 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 8 79 theme intestinal 1476:1485 arg1 cells 1498:1502 intestinal epithelial cells 1476:1502 intestinal epithelial cells (IECs) 1476:1509 Furthermore, we show that MUC3A, MUC3B, MUC12, and MUC17 in the human MUC3 cluster are expressed in intestinal epithelial cells (IECs). 36256656 8 79 theme intestinal 1476:1485 arg1 IECs 1505:1508 IECs 1505:1508 IECs 1505:1508 Furthermore, we show that MUC3A, MUC3B, MUC12, and MUC17 in the human MUC3 cluster are expressed in intestinal epithelial cells (IECs). 36256656 6 80 theme genome 1010:1015 arg1 assembly 1017:1024 a recent human genome assembly 995:1024 a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster 995:1212 Here we leveraged a recent human genome assembly to characterize a previously unmapped MUC3B gene located at the q22 locus on chromosome 7, within a cluster of four structurally related membrane mucin genes that we name the MUC3 cluster. 36256656 4 81 theme standard 797:804 arg1 technologies 817:828 standard sequencing technologies 797:828 standard sequencing technologies 797:828 However, the repetitive nature of mucin domains makes them prone to recombination and renders their genetic sequences particularly difficult to read with standard sequencing technologies. 36256656 11 82 theme used 1860:1863 arg1 organoids 1910:1918 human intestinal organoids 1893:1918 human intestinal organoids 1893:1918 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 11 82 theme used 1860:1863 arg1 models 1878:1883 widely used experimental models 1853:1883 widely used experimental models such as human intestinal organoids and genetic mouse models 1853:1943 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 11 82 theme used 1860:1863 arg1 models 1938:1943 genetic mouse models 1924:1943 genetic mouse models 1924:1943 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 11 83 theme mucin 1830:1834 arg1 function 1841:1848 intestinal mucin gene function 1819:1848 intestinal mucin gene function 1819:1848 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 36256656 0 84 theme MUC3B 15:19 arg1 gene 21:24 a MUC3B gene 13:24 a MUC3B gene 13:24 Discovery of a MUC3B gene reconstructs the membrane mucin gene cluster on human chromosome 7. 36256656 1 85 theme barriers 273:280 arg1 formation 238:246 the formation 234:246 the formation of selective biochemical barriers against harmful microorganisms and molecules 234:325 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 9 86 theme genetic 1542:1548 arg1 gaps 1550:1553 existing genetic gaps 1533:1553 existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates 1533:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 5 87 theme human 844:848 arg1 genes 856:860 human mucin genes 844:860 human mucin genes 844:860 As a result, human mucin genes suffer from significant sequence gaps that have hampered the investigation of gene function in health and disease. 36256656 2 88 theme mucins 368:373 arg1 group 359:363 a distinct group 348:363 a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment 348:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 2 88 theme mucins 368:373 arg1 mucins 337:342 Membrane mucins 328:342 Membrane mucins 328:342 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 2 88 theme mucins 368:373 arg1 mucins 368:373 mucins 368:373 mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment 368:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 1 89 theme harmful 290:296 arg1 microorganisms 298:311 harmful microorganisms 290:311 harmful microorganisms 290:311 Human tissue surfaces are coated with mucins, a family of macromolecular sugar-laden proteins serving diverse functions from lubrication to the formation of selective biochemical barriers against harmful microorganisms and molecules. 36256656 2 90 theme epithelial 396:405 arg1 surfaces 412:419 epithelial cell surfaces 396:419 epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment 396:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 0 91 theme membrane 43:50 arg1 cluster 63:69 the membrane mucin gene cluster 39:69 the membrane mucin gene cluster on human chromosome 7 39:91 Discovery of a MUC3B gene reconstructs the membrane mucin gene cluster on human chromosome 7. 36256656 9 92 theme MUC3 1562:1565 arg1 cluster 1567:1573 the MUC3 cluster 1558:1573 the MUC3 cluster which is a conserved genetic unit in vertebrates 1558:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 9 92 theme MUC3 1562:1565 arg1 unit 1604:1607 a conserved genetic unit 1584:1607 a conserved genetic unit in vertebrates 1584:1622 Our results complete existing genetic gaps in the MUC3 cluster which is a conserved genetic unit in vertebrates. 36256656 7 93 theme known 1274:1278 arg1 gene 1286:1289 the known MUC3A gene 1270:1289 the known MUC3A gene 1270:1289 We found that MUC3B shares high sequence identity with the known MUC3A gene and that the two genes are governed by evolutionarily conserved regulatory elements. 36256656 3 94 theme mucin 500:504 arg1 proteins 506:513 All mucin proteins 496:513 All mucin proteins 496:513 All mucin proteins carry long stretches of tandemly repeated sequences that undergo extensive O-linked glycosylation to form linear mucin domains. 36256656 2 95 theme Membrane 328:335 arg1 group 359:363 a distinct group 348:363 a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment 348:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 2 95 theme Membrane 328:335 arg1 mucins 337:342 Membrane mucins 328:342 Membrane mucins 328:342 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 2 95 theme Membrane 328:335 arg1 mucins 368:373 mucins 368:373 mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment 368:493 Membrane mucins are a distinct group of mucins that are attached to epithelial cell surfaces where they create a dense glycocalyx facing the extracellular environment. 36256656 4 96 theme repetitive 656:665 arg1 nature 667:672 the repetitive nature 652:672 the repetitive nature of mucin domains 652:689 However, the repetitive nature of mucin domains makes them prone to recombination and renders their genetic sequences particularly difficult to read with standard sequencing technologies. 36256656 7 97 theme sequence 1247:1254 arg1 identity 1256:1263 high sequence identity 1242:1263 high sequence identity 1242:1263 We found that MUC3B shares high sequence identity with the known MUC3A gene and that the two genes are governed by evolutionarily conserved regulatory elements. 36256656 11 98 theme gene 1836:1839 arg1 function 1841:1848 intestinal mucin gene function 1819:1848 intestinal mucin gene function 1819:1848 Moreover, our study provides the basis for the exploration of intestinal mucin gene function in widely used experimental models such as human intestinal organoids and genetic mouse models. 35874700 5 0 theme high-fat 772:779 arg1 HFD 787:789 HFD 787:789 HFD 787:789 Treg cell-specific OGT deficiency renders mice more vulnerable to high-fat diet (HFD)-induced adiposity and insulin resistance. 35874700 5 0 theme high-fat 772:779 arg1 diet 781:784 high-fat diet 772:784 high-fat diet (HFD) 772:790 Treg cell-specific OGT deficiency renders mice more vulnerable to high-fat diet (HFD)-induced adiposity and insulin resistance. 35874700 0 1 from Axis 13:16 arg1 Cells 34:38 Regulatory T Cells 21:38 Regulatory T Cells 21:38 An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism. 35874700 1 2 theme emerging 131:138 arg1 effects 140:146 emerging effects 131:146 emerging effects 131:146 The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. 35874700 0 3 theme Iron 60:63 arg1 Metabolism 65:74 Iron Metabolism 60:74 Iron Metabolism 60:74 An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism. 35874700 6 4 theme tissue 925:930 arg1 expansion 932:940 adipose tissue expansion 917:940 adipose tissue expansion 917:940 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 7 5 theme OGT-STAT5 1143:1151 arg1 axis 1153:1156 the OGT-STAT5 axis 1139:1156 the OGT-STAT5 axis to combat obesity and related metabolic disorders 1139:1206 Treg cell function can be augmented by targeting the OGT-STAT5 axis to combat obesity and related metabolic disorders. 35874700 4 6 theme metabolic 683:691 arg1 homeostasis 693:703 metabolic homeostasis 683:703 metabolic homeostasis 683:703 Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. 35874700 2 7 with coping 278:283 arg1 insults 301:307 obesogenic insults 290:307 obesogenic insults 290:307 However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. 35874700 6 8 theme adipose 917:923 arg1 expansion 932:940 adipose tissue expansion 917:940 adipose tissue expansion 917:940 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 4 9 theme transferase 595:605 arg1 axis 619:622 the O-GlcNAc transferase (OGT)-STAT5 axis 582:622 the O-GlcNAc transferase (OGT)-STAT5 axis 582:622 Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. 35874700 2 10 theme cells 269:273 arg1 regulation 226:235 the metabolic regulation and effector mechanisms 212:259 regulation 226:235 However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. 35874700 2 10 theme cells 269:273 arg1 mechanisms 250:259 the metabolic regulation and effector mechanisms 212:259 mechanisms 250:259 However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. 35874700 4 11 theme O-GlcNAc 586:593 arg1 OGT 608:610 OGT 608:610 OGT 608:610 Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. 35874700 4 11 theme O-GlcNAc 586:593 arg1 transferase 595:605 O-GlcNAc transferase 586:605 the O-GlcNAc transferase (OGT)-STAT5 axis 582:622 Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. 35874700 3 12 theme cell 465:468 arg1 identity 470:477 Treg cell identity 460:477 Treg cell identity 460:477 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 2 13 theme Treg 264:267 arg1 cells 269:273 Treg cells 264:273 Treg cells 264:273 However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. 35874700 4 14 theme Treg 668:671 arg1 cells 673:677 Treg cells 668:677 Treg cells 668:677 Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. 35874700 6 15 theme systemic 1067:1074 arg1 storage 1081:1087 systemic iron storage 1067:1087 systemic iron storage 1067:1087 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 5 16 theme -induced 791:798 arg1 adiposity 800:808 high-fat diet (HFD)-induced adiposity 772:808 high-fat diet (HFD)-induced adiposity 772:808 Treg cell-specific OGT deficiency renders mice more vulnerable to high-fat diet (HFD)-induced adiposity and insulin resistance. 35874700 3 17 theme O-linked 395:402 arg1 O-GlcNAc 425:432 O-GlcNAc 425:432 O-GlcNAc 425:432 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 3 17 theme O-linked 395:402 arg1 N-Acetylglucosamine 404:422 O-linked N-Acetylglucosamine 395:422 the O-linked N-Acetylglucosamine (O-GlcNAc) signaling 391:443 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 7 18 theme cell 1095:1098 arg1 function 1100:1107 Treg cell function 1090:1107 Treg cell function 1090:1107 Treg cell function can be augmented by targeting the OGT-STAT5 axis to combat obesity and related metabolic disorders. 35874700 1 19 theme adipose 151:157 arg1 homeostasis 166:176 adipose tissue homeostasis 151:176 adipose tissue homeostasis 151:176 The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. 35874700 0 20 theme OGT-STAT5 3:11 arg1 Axis 13:16 An OGT-STAT5 Axis 0:16 An OGT-STAT5 Axis in Regulatory T Cells 0:38 An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism. 35874700 4 21 theme immunomodulatory 639:654 arg1 function 656:663 the immunomodulatory function 635:663 the immunomodulatory function of Treg cells for metabolic homeostasis 635:703 Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. 35874700 7 22 theme metabolic 1188:1196 arg1 disorders 1198:1206 related metabolic disorders 1180:1206 related metabolic disorders 1180:1206 Treg cell function can be augmented by targeting the OGT-STAT5 axis to combat obesity and related metabolic disorders. 35874700 1 23 theme tissue 159:164 arg1 homeostasis 166:176 adipose tissue homeostasis 151:176 adipose tissue homeostasis 151:176 The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. 35874700 2 24 theme obesogenic 290:299 arg1 insults 301:307 obesogenic insults 290:307 obesogenic insults 290:307 However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. 35874700 5 25 theme insulin 814:820 arg1 resistance 822:831 insulin resistance 814:831 insulin resistance 814:831 Treg cell-specific OGT deficiency renders mice more vulnerable to high-fat diet (HFD)-induced adiposity and insulin resistance. 35874700 6 26 theme HFD 991:993 arg1 feeding 995:1001 HFD feeding 991:1001 HFD feeding 991:1001 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 7 27 theme Treg 1090:1093 arg1 function 1100:1107 Treg cell function 1090:1107 Treg cell function 1090:1107 Treg cell function can be augmented by targeting the OGT-STAT5 axis to combat obesity and related metabolic disorders. 35874700 6 28 from activation 865:874 arg1 cells 884:888 Treg cells 879:888 Treg cells 879:888 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 1 29 theme immunosuppressive 81:97 arg1 cells 119:123 The immunosuppressive regulatory T (Treg) cells 77:123 The immunosuppressive regulatory T (Treg) cells 77:123 The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. 35874700 2 30 from regulation 226:235 arg1 coping 278:283 coping 278:283 coping with obesogenic insults 278:307 However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. 35874700 3 31 theme Treg 460:463 arg1 identity 470:477 Treg cell identity 460:477 Treg cell identity 460:477 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 7 32 theme related 1180:1186 arg1 disorders 1198:1206 related metabolic disorders 1180:1206 related metabolic disorders 1180:1206 Treg cell function can be augmented by targeting the OGT-STAT5 axis to combat obesity and related metabolic disorders. 35874700 3 33 theme STAT5 523:527 arg1 O-GlcNAcylation 529:543 STAT5 O-GlcNAcylation 523:543 STAT5 O-GlcNAcylation 523:543 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 6 34 theme Treg 879:882 arg1 cells 884:888 Treg cells 879:888 Treg cells 879:888 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 1 35 theme regulatory 99:108 arg1 cells 119:123 The immunosuppressive regulatory T (Treg) cells 77:123 The immunosuppressive regulatory T (Treg) cells 77:123 The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. 35874700 2 36 from mechanisms 250:259 arg1 coping 278:283 coping 278:283 coping with obesogenic insults 278:307 However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. 35874700 1 37 theme systemic 182:189 arg1 metabolism 191:200 systemic metabolism 182:200 systemic metabolism 182:200 The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. 35874700 0 38 theme T 32:32 arg1 Cells 34:38 Regulatory T Cells 21:38 Regulatory T Cells 21:38 An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism. 35874700 5 39 theme cell-specific 711:723 arg1 deficiency 729:738 Treg cell-specific OGT deficiency 706:738 Treg cell-specific OGT deficiency 706:738 Treg cell-specific OGT deficiency renders mice more vulnerable to high-fat diet (HFD)-induced adiposity and insulin resistance. 35874700 2 40 theme metabolic 216:224 arg1 regulation 226:235 the metabolic regulation and effector mechanisms 212:259 regulation 226:235 However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. 35874700 0 41 theme Regulatory 21:30 arg1 Cells 34:38 Regulatory T Cells 21:38 Regulatory T Cells 21:38 An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism. 35874700 6 42 theme insulin 967:973 arg1 metabolism 975:984 impaired glucose and insulin metabolism 946:984 impaired glucose and insulin metabolism 946:984 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 3 43 theme N-Acetylglucosamine 404:422 arg1 signaling 435:443 the O-linked N-Acetylglucosamine (O-GlcNAc) signaling 391:443 the O-linked N-Acetylglucosamine (O-GlcNAc) signaling 391:443 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 6 44 theme adipose 1027:1033 arg1 uptake 1041:1046 adipose lipid uptake 1027:1046 adipose lipid uptake 1027:1046 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 3 45 theme suppressor 498:507 arg1 function 509:516 Treg suppressor function 493:516 Treg suppressor function 493:516 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 6 46 theme STAT5 859:863 arg1 activation 865:874 constitutive STAT5 activation 846:874 constitutive STAT5 activation in Treg cells 846:888 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 3 47 link O-linked 395:402 arg1 O-GlcNAc 425:432 O-GlcNAc 425:432 O-GlcNAc 425:432 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 3 47 link O-linked 395:402 arg1 N-Acetylglucosamine 404:422 O-linked N-Acetylglucosamine 395:422 the O-linked N-Acetylglucosamine (O-GlcNAc) signaling 391:443 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 1 48 theme T 110:110 arg1 cells 119:123 The immunosuppressive regulatory T (Treg) cells 77:123 The immunosuppressive regulatory T (Treg) cells 77:123 The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. 35874700 5 49 theme OGT 725:727 arg1 deficiency 729:738 Treg cell-specific OGT deficiency 706:738 Treg cell-specific OGT deficiency 706:738 Treg cell-specific OGT deficiency renders mice more vulnerable to high-fat diet (HFD)-induced adiposity and insulin resistance. 35874700 6 50 theme glucose 955:961 arg1 metabolism 975:984 impaired glucose and insulin metabolism 946:984 impaired glucose and insulin metabolism 946:984 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 6 51 theme constitutive 846:857 arg1 activation 865:874 constitutive STAT5 activation 846:874 constitutive STAT5 activation in Treg cells 846:888 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 3 52 theme Treg 493:496 arg1 function 509:516 Treg suppressor function 493:516 Treg suppressor function 493:516 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 6 53 theme impaired 946:953 arg1 metabolism 975:984 impaired glucose and insulin metabolism 946:984 impaired glucose and insulin metabolism 946:984 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 1 54 theme Treg 113:116 arg1 cells 119:123 The immunosuppressive regulatory T (Treg) cells 77:123 The immunosuppressive regulatory T (Treg) cells 77:123 The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. 35874700 2 55 theme effector 241:248 arg1 mechanisms 250:259 the metabolic regulation and effector mechanisms 212:259 mechanisms 250:259 However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. 35874700 4 56 theme cells 673:677 arg1 function 656:663 the immunomodulatory function 635:663 the immunomodulatory function of Treg cells for metabolic homeostasis 635:703 Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. 35874700 6 57 theme lipid 1035:1039 arg1 uptake 1041:1046 adipose lipid uptake 1027:1046 adipose lipid uptake 1027:1046 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 6 58 theme iron 1076:1079 arg1 storage 1081:1087 systemic iron storage 1067:1087 systemic iron storage 1067:1087 Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. 35874700 3 59 theme signaling 435:443 arg1 role 383:386 an indispensable role 366:386 an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function 366:516 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35874700 4 60 theme -STAT5 612:617 arg1 axis 619:622 the O-GlcNAc transferase (OGT)-STAT5 axis 582:622 the O-GlcNAc transferase (OGT)-STAT5 axis 582:622 Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. 35874700 3 61 theme indispensable 369:381 arg1 role 383:386 an indispensable role 366:386 an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function 366:516 We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. 35819414 5 0 theme labeling 804:811 arg1 set 965:967 a set 963:967 a set of tools called "GlycoID 963:992 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 5 0 theme labeling 804:811 arg1 tools 972:976 tools 972:976 tools called "GlycoID 972:992 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 5 0 theme labeling 804:811 arg1 strategy 813:820 a labeling strategy 802:820 a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells 802:960 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 4 1 with patterns 751:758 arg1 control 780:786 spatiotemporal control 765:786 spatiotemporal control 765:786 The objective of this study was to create intracellular proximity labeling tools to identify functional changes in O-GlcNAc patterns with spatiotemporal control. 35819414 3 2 with events 517:522 arg1 control 558:564 spatial control 550:564 spatial control over subcellular locations 550:591 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 3 2 with events 517:522 arg1 control 602:608 time control 597:608 time control 597:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 3 2 with events 517:522 arg1 strategies 538:547 chemical strategies 529:547 chemical strategies: spatial control over subcellular locations and time control 529:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 6 3 theme O-GlcNAc 1080:1087 arg1 proteins 1089:1096 O-GlcNAc proteins 1080:1096 O-GlcNAc proteins 1080:1096 Localized variants to the nucleus and cytosol, nuc-GlycoID and cyt-GlycoID, labeled O-GlcNAc proteins and their interactomes in subcellular space. 35819414 7 4 theme signal 1266:1271 arg1 initiation 1273:1282 signal initiation 1266:1282 signal initiation 1266:1282 Labeling during insulin and serum stimulation revealed functional changes in O-GlcNAc proteins as soon as 30 min following signal initiation. 35819414 10 5 theme O-GlcNAc-driven 1740:1754 arg1 mechanisms 1756:1765 O-GlcNAc-driven mechanisms 1740:1765 O-GlcNAc-driven mechanisms 1740:1765 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35819414 7 6 theme serum 1171:1175 arg1 stimulation 1177:1187 serum stimulation 1171:1187 serum stimulation 1171:1187 Labeling during insulin and serum stimulation revealed functional changes in O-GlcNAc proteins as soon as 30 min following signal initiation. 35819414 2 7 theme protein 362:368 arg1 sites 370:374 diverse protein sites 354:374 diverse protein sites 354:374 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 10 8 theme data 1683:1686 arg1 sets 1688:1691 Our functional O-GlcNAc data sets 1659:1691 Our functional O-GlcNAc data sets in human cells 1659:1706 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35819414 10 8 theme data 1683:1686 arg1 resource 1727:1734 a valuable resource 1716:1734 a valuable resource for O-GlcNAc-driven mechanisms 1716:1765 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35819414 7 9 from changes 1209:1215 arg1 proteins 1229:1236 O-GlcNAc proteins 1220:1236 O-GlcNAc proteins 1220:1236 Labeling during insulin and serum stimulation revealed functional changes in O-GlcNAc proteins as soon as 30 min following signal initiation. 35819414 3 10 theme chemical 529:536 arg1 control 558:564 spatial control 550:564 spatial control over subcellular locations 550:591 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 3 10 theme chemical 529:536 arg1 control 602:608 time control 597:608 time control 597:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 3 10 theme chemical 529:536 arg1 strategies 538:547 chemical strategies 529:547 chemical strategies: spatial control over subcellular locations and time control 529:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 8 11 theme O-GlcNAc 1406:1413 arg1 proteins 1415:1422 O-GlcNAc proteins 1406:1422 O-GlcNAc proteins 1406:1422 We demonstrated using proteomic analysis that the GlycoID strategy captured O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions. 35819414 8 12 theme protein-protein 1445:1459 arg1 interactions 1461:1472 their associated protein-protein interactions 1428:1472 their associated protein-protein interactions 1428:1472 We demonstrated using proteomic analysis that the GlycoID strategy captured O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions. 35819414 2 13 link O-linked 277:284 arg1 O-GlcNAc 307:314 O-GlcNAc 307:314 O-GlcNAc 307:314 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 2 13 link O-linked 277:284 arg1 N-acetylglucosamine 286:304 O-linked N-acetylglucosamine 277:304 O-linked N-acetylglucosamine (O-GlcNAc) 277:315 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 2 13 link O-linked 277:284 arg1 response 381:388 a response 379:388 a response to fluctuating nutrient levels, stressors, and signaling cues 379:450 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 0 14 theme Cellular 102:109 arg1 Signaling 111:119 Cellular Signaling 102:119 Cellular Signaling 102:119 Spatiotemporal Proximity Labeling Tools to Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling. 35819414 9 15 theme cell 1642:1645 arg1 regulation 1647:1656 glycobiological cell regulation 1626:1656 glycobiological cell regulation 1626:1656 The ability to follow changes in O-GlcNAc hubs during physiological events such as insulin signaling allows these tools to determine the mechanisms of glycobiological cell regulation. 35819414 8 16 theme O-GlcNAcylated 1361:1374 arg1 " 1390:1390 O-GlcNAcylated "activity hubs" 1361:1390 O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions 1361:1472 We demonstrated using proteomic analysis that the GlycoID strategy captured O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions. 35819414 4 17 theme functional 720:729 arg1 changes 731:737 functional changes 720:737 functional changes in O-GlcNAc patterns with spatiotemporal control 720:786 The objective of this study was to create intracellular proximity labeling tools to identify functional changes in O-GlcNAc patterns with spatiotemporal control. 35819414 2 18 theme diverse 354:360 arg1 sites 370:374 diverse protein sites 354:374 diverse protein sites 354:374 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 5 19 theme protein 879:885 arg1 conjugation 894:904 rapid protein biotin conjugation 873:904 rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells 873:960 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 4 20 theme study 649:653 arg1 objective 631:639 The objective 627:639 The objective of this study 627:653 The objective of this study was to create intracellular proximity labeling tools to identify functional changes in O-GlcNAc patterns with spatiotemporal control. 35819414 9 21 theme O-GlcNAc 1508:1515 arg1 hubs 1517:1520 O-GlcNAc hubs 1508:1520 O-GlcNAc hubs 1508:1520 The ability to follow changes in O-GlcNAc hubs during physiological events such as insulin signaling allows these tools to determine the mechanisms of glycobiological cell regulation. 35819414 8 22 theme proteomic 1307:1315 arg1 analysis 1317:1324 proteomic analysis that the GlycoID strategy captured O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions 1307:1472 proteomic analysis that the GlycoID strategy captured O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions 1307:1472 We demonstrated using proteomic analysis that the GlycoID strategy captured O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions. 35819414 2 23 theme nutrient 405:412 arg1 levels 414:419 fluctuating nutrient levels 393:419 fluctuating nutrient levels 393:419 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 5 24 theme TurboID 835:841 arg1 system 862:867 the TurboID proximity labeling system 831:867 the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells 831:960 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 7 25 theme functional 1198:1207 arg1 changes 1209:1215 functional changes 1198:1215 functional changes in O-GlcNAc proteins as soon as 30 min following signal initiation 1198:1282 Labeling during insulin and serum stimulation revealed functional changes in O-GlcNAc proteins as soon as 30 min following signal initiation. 35819414 3 26 theme spatial 550:556 arg1 control 558:564 spatial control 550:564 spatial control over subcellular locations 550:591 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 3 26 theme spatial 550:556 arg1 strategies 538:547 chemical strategies 529:547 chemical strategies: spatial control over subcellular locations and time control 529:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 3 27 theme functional 497:506 arg1 events 517:522 functional O-GlcNAc events 497:522 functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control 497:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 2 28 theme fluctuating 393:403 arg1 levels 414:419 fluctuating nutrient levels 393:419 fluctuating nutrient levels 393:419 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 0 29 theme Proximity 15:23 arg1 Labeling 25:32 Spatiotemporal Proximity Labeling 0:32 Spatiotemporal Proximity Labeling 0:32 Spatiotemporal Proximity Labeling Tools to Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling. 35819414 2 30 attach removed 341:347 arg2 response 381:388 a response 379:388 a response to fluctuating nutrient levels, stressors, and signaling cues 379:450 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 2 30 attach removed 341:347 arg2 N-acetylglucosamine 286:304 O-linked N-acetylglucosamine 277:304 O-linked N-acetylglucosamine (O-GlcNAc) 277:315 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 2 30 attach removed 341:347 arg2 O-GlcNAc 307:314 O-GlcNAc 307:314 O-GlcNAc 307:314 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 2 30 attach removed 341:347 arg1 sites 370:374 diverse protein sites 354:374 diverse protein sites 354:374 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 10 31 theme human 1696:1700 arg1 cells 1702:1706 human cells 1696:1706 human cells 1696:1706 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35819414 8 32 theme associated 1434:1443 arg1 interactions 1461:1472 their associated protein-protein interactions 1428:1472 their associated protein-protein interactions 1428:1472 We demonstrated using proteomic analysis that the GlycoID strategy captured O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions. 35819414 6 33 theme subcellular 1124:1134 arg1 space 1136:1140 subcellular space 1124:1140 subcellular space 1124:1140 Localized variants to the nucleus and cytosol, nuc-GlycoID and cyt-GlycoID, labeled O-GlcNAc proteins and their interactomes in subcellular space. 35819414 5 34 theme O-GlcNAc 918:925 arg1 modifications 935:947 O-GlcNAc protein modifications 918:947 O-GlcNAc protein modifications 918:947 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 0 35 theme Spatiotemporal 0:13 arg1 Labeling 25:32 Spatiotemporal Proximity Labeling 0:32 Spatiotemporal Proximity Labeling 0:32 Spatiotemporal Proximity Labeling Tools to Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling. 35819414 6 36 from proteins 1089:1096 arg1 space 1136:1140 subcellular space 1124:1140 subcellular space 1124:1140 Localized variants to the nucleus and cytosol, nuc-GlycoID and cyt-GlycoID, labeled O-GlcNAc proteins and their interactomes in subcellular space. 35819414 3 37 theme time 597:600 arg1 control 602:608 time control 597:608 time control 597:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 3 37 theme time 597:600 arg1 strategies 538:547 chemical strategies 529:547 chemical strategies: spatial control over subcellular locations and time control 529:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 4 38 theme labeling 693:700 arg1 tools 702:706 intracellular proximity labeling tools 669:706 intracellular proximity labeling tools 669:706 The objective of this study was to create intracellular proximity labeling tools to identify functional changes in O-GlcNAc patterns with spatiotemporal control. 35819414 2 39 theme signaling 437:445 arg1 cues 447:450 signaling cues 437:450 signaling cues 437:450 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 5 40 theme labeling 853:860 arg1 system 862:867 the TurboID proximity labeling system 831:867 the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells 831:960 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 6 41 from interactomes 1108:1119 arg1 space 1136:1140 subcellular space 1124:1140 subcellular space 1124:1140 Localized variants to the nucleus and cytosol, nuc-GlycoID and cyt-GlycoID, labeled O-GlcNAc proteins and their interactomes in subcellular space. 35819414 3 42 theme subcellular 571:581 arg1 locations 583:591 subcellular locations 571:591 subcellular locations 571:591 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 5 43 theme rapid 873:877 arg1 conjugation 894:904 rapid protein biotin conjugation 873:904 rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells 873:960 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 4 44 theme spatiotemporal 765:778 arg1 control 780:786 spatiotemporal control 765:786 spatiotemporal control 765:786 The objective of this study was to create intracellular proximity labeling tools to identify functional changes in O-GlcNAc patterns with spatiotemporal control. 35819414 6 45 theme Localized 996:1004 arg1 nuc-GlycoID 1043:1053 nuc-GlycoID 1043:1053 nuc-GlycoID 1043:1053 Localized variants to the nucleus and cytosol, nuc-GlycoID and cyt-GlycoID, labeled O-GlcNAc proteins and their interactomes in subcellular space. 35819414 6 45 theme Localized 996:1004 arg1 variants 1006:1013 Localized variants 996:1013 Localized variants to the nucleus and cytosol 996:1040 Localized variants to the nucleus and cytosol, nuc-GlycoID and cyt-GlycoID, labeled O-GlcNAc proteins and their interactomes in subcellular space. 35819414 6 45 theme Localized 996:1004 arg1 cyt-GlycoID 1059:1069 cyt-GlycoID 1059:1069 cyt-GlycoID 1059:1069 Localized variants to the nucleus and cytosol, nuc-GlycoID and cyt-GlycoID, labeled O-GlcNAc proteins and their interactomes in subcellular space. 35819414 1 46 with modification 225:236 arg1 sugars 258:263 monosaccharide sugars 243:263 monosaccharide sugars 243:263 A fundamental mechanism that all eukaryotic cells use to adapt to their environment is dynamic protein modification with monosaccharide sugars. 35819414 3 47 dep strategies 538:547 arg1 control 558:564 spatial control 550:564 spatial control over subcellular locations 550:591 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 3 47 dep strategies 538:547 arg1 control 602:608 time control 597:608 time control 597:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 3 47 dep strategies 538:547 arg1 strategies 538:547 chemical strategies 529:547 chemical strategies: spatial control over subcellular locations and time control 529:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 1 48 theme dynamic 209:215 arg1 mechanism 136:144 A fundamental mechanism 122:144 A fundamental mechanism that all eukaryotic cells use to adapt to their environment 122:204 A fundamental mechanism that all eukaryotic cells use to adapt to their environment is dynamic protein modification with monosaccharide sugars. 35819414 1 48 theme dynamic 209:215 arg1 modification 225:236 dynamic protein modification 209:236 dynamic protein modification with monosaccharide sugars 209:263 A fundamental mechanism that all eukaryotic cells use to adapt to their environment is dynamic protein modification with monosaccharide sugars. 35819414 0 49 theme Track 43:47 arg1 Hubs 90:93 Track GlcNAc Sugar-Modified Functional Protein Hubs 43:93 Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling 43:119 Spatiotemporal Proximity Labeling Tools to Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling. 35819414 5 50 dep developed 792:800 arg1 " 994:994 " 994:994 " 994:994 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 5 51 theme biotin 887:892 arg1 conjugation 894:904 rapid protein biotin conjugation 873:904 rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells 873:960 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 5 52 theme protein 927:933 arg1 modifications 935:947 O-GlcNAc protein modifications 918:947 O-GlcNAc protein modifications 918:947 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 1 53 theme protein 217:223 arg1 mechanism 136:144 A fundamental mechanism 122:144 A fundamental mechanism that all eukaryotic cells use to adapt to their environment 122:204 A fundamental mechanism that all eukaryotic cells use to adapt to their environment is dynamic protein modification with monosaccharide sugars. 35819414 1 53 theme protein 217:223 arg1 modification 225:236 dynamic protein modification 209:236 dynamic protein modification with monosaccharide sugars 209:263 A fundamental mechanism that all eukaryotic cells use to adapt to their environment is dynamic protein modification with monosaccharide sugars. 35819414 4 54 theme proximity 683:691 arg1 tools 702:706 intracellular proximity labeling tools 669:706 intracellular proximity labeling tools 669:706 The objective of this study was to create intracellular proximity labeling tools to identify functional changes in O-GlcNAc patterns with spatiotemporal control. 35819414 9 55 from changes 1497:1503 arg1 hubs 1517:1520 O-GlcNAc hubs 1508:1520 O-GlcNAc hubs 1508:1520 The ability to follow changes in O-GlcNAc hubs during physiological events such as insulin signaling allows these tools to determine the mechanisms of glycobiological cell regulation. 35819414 8 56 theme activity 1377:1384 arg1 " 1390:1390 O-GlcNAcylated "activity hubs" 1361:1390 O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions 1361:1472 We demonstrated using proteomic analysis that the GlycoID strategy captured O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions. 35819414 0 57 theme Sugar-Modified 56:69 arg1 Hubs 90:93 Track GlcNAc Sugar-Modified Functional Protein Hubs 43:93 Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling 43:119 Spatiotemporal Proximity Labeling Tools to Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling. 35819414 7 58 dep soon 1241:1244 arg1 as 1246:1247 as 1246:1247 as 1246:1247 Labeling during insulin and serum stimulation revealed functional changes in O-GlcNAc proteins as soon as 30 min following signal initiation. 35819414 9 59 theme insulin 1558:1564 arg1 signaling 1566:1574 insulin signaling 1558:1574 insulin signaling 1558:1574 The ability to follow changes in O-GlcNAc hubs during physiological events such as insulin signaling allows these tools to determine the mechanisms of glycobiological cell regulation. 35819414 1 60 theme fundamental 124:134 arg1 mechanism 136:144 A fundamental mechanism 122:144 A fundamental mechanism that all eukaryotic cells use to adapt to their environment 122:204 A fundamental mechanism that all eukaryotic cells use to adapt to their environment is dynamic protein modification with monosaccharide sugars. 35819414 1 60 theme fundamental 124:134 arg1 modification 225:236 dynamic protein modification 209:236 dynamic protein modification with monosaccharide sugars 209:263 A fundamental mechanism that all eukaryotic cells use to adapt to their environment is dynamic protein modification with monosaccharide sugars. 35819414 0 61 theme GlcNAc 49:54 arg1 Hubs 90:93 Track GlcNAc Sugar-Modified Functional Protein Hubs 43:93 Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling 43:119 Spatiotemporal Proximity Labeling Tools to Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling. 35819414 9 62 theme glycobiological 1626:1640 arg1 regulation 1647:1656 glycobiological cell regulation 1626:1656 glycobiological cell regulation 1626:1656 The ability to follow changes in O-GlcNAc hubs during physiological events such as insulin signaling allows these tools to determine the mechanisms of glycobiological cell regulation. 35819414 3 63 theme O-GlcNAc 508:515 arg1 events 517:522 functional O-GlcNAc events 497:522 functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control 497:608 Two aspects remain challenging for tracking functional O-GlcNAc events with chemical strategies: spatial control over subcellular locations and time control during labeling. 35819414 10 64 theme valuable 1718:1725 arg1 resource 1727:1734 a valuable resource 1716:1734 a valuable resource for O-GlcNAc-driven mechanisms 1716:1765 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35819414 10 64 theme valuable 1718:1725 arg1 sets 1688:1691 Our functional O-GlcNAc data sets 1659:1691 Our functional O-GlcNAc data sets in human cells 1659:1706 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35819414 4 65 theme O-GlcNAc 742:749 arg1 patterns 751:758 O-GlcNAc patterns 742:758 O-GlcNAc patterns with spatiotemporal control 742:786 The objective of this study was to create intracellular proximity labeling tools to identify functional changes in O-GlcNAc patterns with spatiotemporal control. 35819414 10 66 from sets 1688:1691 arg1 cells 1702:1706 human cells 1696:1706 human cells 1696:1706 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35819414 2 67 theme O-linked 277:284 arg1 O-GlcNAc 307:314 O-GlcNAc 307:314 O-GlcNAc 307:314 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 2 67 theme O-linked 277:284 arg1 N-acetylglucosamine 286:304 O-linked N-acetylglucosamine 277:304 O-linked N-acetylglucosamine (O-GlcNAc) 277:315 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 2 67 theme O-linked 277:284 arg1 response 381:388 a response 379:388 a response to fluctuating nutrient levels, stressors, and signaling cues 379:450 In humans, O-linked N-acetylglucosamine (O-GlcNAc) is rapidly added to and removed from diverse protein sites as a response to fluctuating nutrient levels, stressors, and signaling cues. 35819414 10 68 theme functional 1663:1672 arg1 sets 1688:1691 Our functional O-GlcNAc data sets 1659:1691 Our functional O-GlcNAc data sets in human cells 1659:1706 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35819414 10 68 theme functional 1663:1672 arg1 resource 1727:1734 a valuable resource 1716:1734 a valuable resource for O-GlcNAc-driven mechanisms 1716:1765 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35819414 8 69 theme GlycoID 1335:1341 arg1 strategy 1343:1350 the GlycoID strategy 1331:1350 the GlycoID strategy 1331:1350 We demonstrated using proteomic analysis that the GlycoID strategy captured O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions. 35819414 8 70 theme hubs 1386:1389 arg1 " 1390:1390 O-GlcNAcylated "activity hubs" 1361:1390 O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions 1361:1472 We demonstrated using proteomic analysis that the GlycoID strategy captured O-GlcNAcylated "activity hubs" consisting of O-GlcNAc proteins and their associated protein-protein interactions. 35819414 5 71 theme tools 972:976 arg1 set 965:967 a set 963:967 a set of tools called "GlycoID 963:992 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 5 71 theme tools 972:976 arg1 strategy 813:820 a labeling strategy 802:820 a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells 802:960 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 5 71 theme tools 972:976 arg1 tools 972:976 tools 972:976 tools called "GlycoID 972:992 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 1 72 theme monosaccharide 243:256 arg1 sugars 258:263 monosaccharide sugars 243:263 monosaccharide sugars 243:263 A fundamental mechanism that all eukaryotic cells use to adapt to their environment is dynamic protein modification with monosaccharide sugars. 35819414 0 73 theme Protein 82:88 arg1 Hubs 90:93 Track GlcNAc Sugar-Modified Functional Protein Hubs 43:93 Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling 43:119 Spatiotemporal Proximity Labeling Tools to Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling. 35819414 1 74 theme eukaryotic 155:164 arg1 cells 166:170 all eukaryotic cells 151:170 all eukaryotic cells 151:170 A fundamental mechanism that all eukaryotic cells use to adapt to their environment is dynamic protein modification with monosaccharide sugars. 35819414 4 75 theme intracellular 669:681 arg1 tools 702:706 intracellular proximity labeling tools 669:706 intracellular proximity labeling tools 669:706 The objective of this study was to create intracellular proximity labeling tools to identify functional changes in O-GlcNAc patterns with spatiotemporal control. 35819414 0 76 theme Functional 71:80 arg1 Hubs 90:93 Track GlcNAc Sugar-Modified Functional Protein Hubs 43:93 Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling 43:119 Spatiotemporal Proximity Labeling Tools to Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling. 35819414 9 77 theme physiological 1529:1541 arg1 events 1543:1548 physiological events 1529:1548 physiological events such as insulin signaling 1529:1574 The ability to follow changes in O-GlcNAc hubs during physiological events such as insulin signaling allows these tools to determine the mechanisms of glycobiological cell regulation. 35819414 9 77 theme physiological 1529:1541 arg1 signaling 1566:1574 insulin signaling 1558:1574 insulin signaling 1558:1574 The ability to follow changes in O-GlcNAc hubs during physiological events such as insulin signaling allows these tools to determine the mechanisms of glycobiological cell regulation. 35819414 7 78 theme O-GlcNAc 1220:1227 arg1 proteins 1229:1236 O-GlcNAc proteins 1220:1236 O-GlcNAc proteins 1220:1236 Labeling during insulin and serum stimulation revealed functional changes in O-GlcNAc proteins as soon as 30 min following signal initiation. 35819414 9 79 theme regulation 1647:1656 arg1 mechanisms 1612:1621 the mechanisms 1608:1621 the mechanisms of glycobiological cell regulation 1608:1656 The ability to follow changes in O-GlcNAc hubs during physiological events such as insulin signaling allows these tools to determine the mechanisms of glycobiological cell regulation. 35819414 5 80 theme proximity 843:851 arg1 system 862:867 the TurboID proximity labeling system 831:867 the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells 831:960 We developed a labeling strategy based on the TurboID proximity labeling system for rapid protein biotin conjugation directed to O-GlcNAc protein modifications inside cells, a set of tools called "GlycoID." 35819414 4 81 from changes 731:737 arg1 patterns 751:758 O-GlcNAc patterns 742:758 O-GlcNAc patterns with spatiotemporal control 742:786 The objective of this study was to create intracellular proximity labeling tools to identify functional changes in O-GlcNAc patterns with spatiotemporal control. 35819414 10 82 theme O-GlcNAc 1674:1681 arg1 sets 1688:1691 Our functional O-GlcNAc data sets 1659:1691 Our functional O-GlcNAc data sets in human cells 1659:1706 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35819414 10 82 theme O-GlcNAc 1674:1681 arg1 resource 1727:1734 a valuable resource 1716:1734 a valuable resource for O-GlcNAc-driven mechanisms 1716:1765 Our functional O-GlcNAc data sets in human cells will be a valuable resource for O-GlcNAc-driven mechanisms. 35743252 0 0 theme Volume 85:90 arg1 Overload 92:99 Volume Overload 85:99 Volume Overload 85:99 Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses. 35743252 0 1 from Reversibility 17:29 arg1 Hearts 63:68 Failing Hearts 55:68 Failing Hearts Resulting from Volume Overload 55:99 Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses. 35743252 1 2 theme energy 169:174 arg1 metabolism 176:185 cardiac energy metabolism 161:185 cardiac energy metabolism 161:185 Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). 35743252 8 3 theme Delayed 1307:1313 arg1 correction 1315:1324 Delayed correction 1307:1324 Delayed correction of VO in HF 1307:1336 Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. 35743252 3 4 theme echocardiographic 670:686 arg1 studies 704:710 echocardiographic and hemodynamic studies 670:710 echocardiographic and hemodynamic studies 670:710 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. 35743252 2 5 dep creation 445:452 arg1 the 441:443 the 441:443 the 441:443 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 2 6 theme aortocaval 480:489 arg1 fistula 491:497 aortocaval fistula 480:497 aortocaval fistula 480:497 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 2 7 dep transcriptomics 279:293 arg1 analyses 312:319 analyses 312:319 analyses 312:319 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 7 8 theme genes 1226:1230 arg1 expression 1212:1221 the differential expression 1195:1221 the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF 1195:1304 Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. 35743252 0 9 from Derangements 0:11 arg1 Hearts 63:68 Failing Hearts 55:68 Failing Hearts Resulting from Volume Overload 55:99 Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses. 35743252 8 10 theme acid 1404:1407 arg1 oxidation 1409:1417 fatty acid oxidation 1398:1417 fatty acid oxidation 1398:1417 Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. 35743252 3 11 theme aortocaval 541:550 arg1 fistula 552:558 an aortocaval fistula 538:558 an aortocaval fistula surgery for 8 and 16 weeks 538:585 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. 35743252 3 12 theme fistula 552:558 arg1 surgery 560:566 an aortocaval fistula surgery 538:566 an aortocaval fistula surgery for 8 and 16 weeks 538:585 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. 35743252 2 13 theme cardiac 370:376 arg1 energetics 378:387 cardiac energetics 370:387 cardiac energetics 370:387 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 9 14 theme strategies 1490:1499 arg1 development 1464:1474 the development 1460:1474 the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF 1460:1561 These findings may provide insight into the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF. 35743252 5 15 from Derangements 908:919 arg1 oxidation 935:943 fatty acid oxidation 924:943 fatty acid oxidation 924:943 Derangements in fatty acid oxidation were not prominent until the development of HF, as indicated by the accumulation of acylcarnitines. 35743252 6 16 theme acid 1104:1107 arg1 cycle 1109:1113 the tricarboxylic acid cycle 1086:1113 the tricarboxylic acid cycle 1086:1113 The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. 35743252 5 17 theme fatty 924:928 arg1 oxidation 935:943 fatty acid oxidation 924:943 fatty acid oxidation 924:943 Derangements in fatty acid oxidation were not prominent until the development of HF, as indicated by the accumulation of acylcarnitines. 35743252 6 18 dep expression 1054:1063 arg1 The 1045:1047 The 1045:1047 The 1045:1047 The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. 35743252 6 19 theme cycle 1109:1113 arg1 intermediates 1069:1081 intermediates 1069:1081 intermediates 1069:1081 The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. 35743252 6 19 theme cycle 1109:1113 arg1 expression 1054:1063 gene expression 1049:1063 gene expression 1049:1063 The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. 35743252 6 20 theme tricarboxylic 1090:1102 arg1 cycle 1109:1113 the tricarboxylic acid cycle 1086:1113 the tricarboxylic acid cycle 1086:1113 The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. 35743252 8 21 theme oxidation 1409:1417 arg1 recovery 1361:1368 incomplete recovery 1350:1368 incomplete recovery of defective glycolysis and fatty acid oxidation 1350:1417 Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. 35743252 8 22 theme glycolysis 1383:1392 arg1 recovery 1361:1368 incomplete recovery 1350:1368 incomplete recovery of defective glycolysis and fatty acid oxidation 1350:1417 Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. 35743252 1 23 from Derangements 145:156 arg1 metabolism 176:185 cardiac energy metabolism 161:185 cardiac energy metabolism 161:185 Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). 35743252 2 24 theme rat 394:396 arg1 model 398:402 a rat model 392:402 a rat model of cardiac volume overload (VO) 392:434 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 7 25 theme differential 1199:1210 arg1 expression 1212:1221 the differential expression 1195:1221 the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF 1195:1304 Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. 35743252 7 26 theme VO 1175:1176 arg1 Correction 1161:1170 Correction 1161:1170 Correction of VO 1161:1176 Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. 35743252 8 27 from correction 1315:1324 arg1 HF 1335:1336 HF 1335:1336 HF 1335:1336 Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. 35743252 8 28 theme incomplete 1350:1359 arg1 recovery 1361:1368 incomplete recovery 1350:1368 incomplete recovery of defective glycolysis and fatty acid oxidation 1350:1417 Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. 35743252 9 29 theme metabolic 1523:1531 arg1 derangements 1533:1544 metabolic derangements 1523:1544 metabolic derangements in VO-induced HF 1523:1561 These findings may provide insight into the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF. 35743252 8 30 theme fatty 1398:1402 arg1 oxidation 1409:1417 fatty acid oxidation 1398:1417 fatty acid oxidation 1398:1417 Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. 35743252 8 31 theme defective 1373:1381 arg1 glycolysis 1383:1392 defective glycolysis 1373:1392 defective glycolysis 1373:1392 Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. 35743252 9 32 from derangements 1533:1544 arg1 HF 1560:1561 VO-induced HF 1549:1561 VO-induced HF 1549:1561 These findings may provide insight into the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF. 35743252 0 33 theme Metabolomics 122:133 arg1 Analyses 135:142 Metabolomics Analyses 122:142 Metabolomics Analyses 122:142 Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses. 35743252 7 34 from expression 1212:1221 arg1 HF 1303:1304 HF 1303:1304 HF 1303:1304 Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. 35743252 7 34 from expression 1212:1221 arg1 CH 1289:1290 CH 1289:1290 CH 1289:1290 Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. 35743252 3 35 theme Sprague-Dawley 505:518 arg1 rats 520:523 Male Sprague-Dawley rats 500:523 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks 500:585 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. 35743252 2 36 theme overload 422:429 arg1 model 398:402 a rat model 392:402 a rat model of cardiac volume overload (VO) 392:434 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 0 37 theme Metabolism 41:50 arg1 Reversibility 17:29 Reversibility 17:29 Reversibility 17:29 Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses. 35743252 0 37 theme Metabolism 41:50 arg1 Derangements 0:11 Derangements 0:11 Derangements 0:11 Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses. 35743252 3 38 theme HF 649:650 arg1 characteristics 597:611 characteristics 597:611 characteristics of compensated hypertrophy (CH) and HF 597:650 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. 35743252 2 39 theme volume 415:420 arg1 VO 432:433 VO 432:433 VO 432:433 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 2 39 theme volume 415:420 arg1 overload 422:429 cardiac volume overload 407:429 cardiac volume overload (VO) 407:434 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 2 40 theme subsequent 458:467 arg1 closure 469:475 subsequent closure 458:475 subsequent closure 458:475 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 0 41 theme Energy 34:39 arg1 Metabolism 41:50 Energy Metabolism 34:50 Energy Metabolism 34:50 Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses. 35743252 4 42 theme hexosamine 762:771 arg1 HBP 795:797 HBP 795:797 HBP 795:797 Glycolysis was downregulated and directed to the hexosamine biosynthetic pathway (HBP) and O-linked-N-acetylglucosaminylation in the CH phase and was further suppressed during progression to HF. 35743252 4 42 theme hexosamine 762:771 arg1 pathway 786:792 the hexosamine biosynthetic pathway 758:792 the hexosamine biosynthetic pathway (HBP) 758:798 Glycolysis was downregulated and directed to the hexosamine biosynthetic pathway (HBP) and O-linked-N-acetylglucosaminylation in the CH phase and was further suppressed during progression to HF. 35743252 5 43 theme acylcarnitines 1029:1042 arg1 accumulation 1013:1024 the accumulation 1009:1024 the accumulation of acylcarnitines 1009:1042 Derangements in fatty acid oxidation were not prominent until the development of HF, as indicated by the accumulation of acylcarnitines. 35743252 2 44 theme cardiac 407:413 arg1 VO 432:433 VO 432:433 VO 432:433 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 2 44 theme cardiac 407:413 arg1 overload 422:429 cardiac volume overload 407:429 cardiac volume overload (VO) 407:434 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 0 45 theme Failing 55:61 arg1 Hearts 63:68 Failing Hearts 55:68 Failing Hearts Resulting from Volume Overload 55:99 Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses. 35743252 3 46 theme Male 500:503 arg1 rats 520:523 Male Sprague-Dawley rats 500:523 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks 500:585 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. 35743252 5 47 theme HF 989:990 arg1 development 974:984 the development 970:984 the development of HF 970:990 Derangements in fatty acid oxidation were not prominent until the development of HF, as indicated by the accumulation of acylcarnitines. 35743252 5 48 theme acid 930:933 arg1 oxidation 935:943 fatty acid oxidation 924:943 fatty acid oxidation 924:943 Derangements in fatty acid oxidation were not prominent until the development of HF, as indicated by the accumulation of acylcarnitines. 35743252 9 49 theme VO-induced 1549:1558 arg1 HF 1560:1561 VO-induced HF 1549:1561 VO-induced HF 1549:1561 These findings may provide insight into the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF. 35743252 4 50 theme CH 846:847 arg1 phase 849:853 the CH phase 842:853 the CH phase 842:853 Glycolysis was downregulated and directed to the hexosamine biosynthetic pathway (HBP) and O-linked-N-acetylglucosaminylation in the CH phase and was further suppressed during progression to HF. 35743252 3 51 theme compensated 616:626 arg1 CH 641:642 CH 641:642 CH 641:642 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. 35743252 3 51 theme compensated 616:626 arg1 hypertrophy 628:638 compensated hypertrophy 616:638 compensated hypertrophy (CH) 616:643 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. 35743252 3 52 theme hypertrophy 628:638 arg1 characteristics 597:611 characteristics 597:611 characteristics of compensated hypertrophy (CH) and HF 597:650 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. 35743252 7 53 theme acid 1271:1274 arg1 oxidation 1276:1284 fatty acid oxidation 1265:1284 fatty acid oxidation 1265:1284 Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. 35743252 4 54 theme biosynthetic 773:784 arg1 HBP 795:797 HBP 795:797 HBP 795:797 Glycolysis was downregulated and directed to the hexosamine biosynthetic pathway (HBP) and O-linked-N-acetylglucosaminylation in the CH phase and was further suppressed during progression to HF. 35743252 4 54 theme biosynthetic 773:784 arg1 pathway 786:792 the hexosamine biosynthetic pathway 758:792 the hexosamine biosynthetic pathway (HBP) 758:798 Glycolysis was downregulated and directed to the hexosamine biosynthetic pathway (HBP) and O-linked-N-acetylglucosaminylation in the CH phase and was further suppressed during progression to HF. 35743252 1 55 theme cardiac 161:167 arg1 metabolism 176:185 cardiac energy metabolism 161:185 cardiac energy metabolism 161:185 Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). 35743252 8 56 theme VO 1329:1330 arg1 correction 1315:1324 Delayed correction 1307:1324 Delayed correction of VO in HF 1307:1336 Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. 35743252 1 57 theme heart 239:243 arg1 failure 245:251 heart failure 239:251 heart failure (HF) 239:256 Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). 35743252 1 57 theme heart 239:243 arg1 HF 254:255 HF 254:255 HF 254:255 Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). 35743252 9 58 theme innovative 1479:1488 arg1 strategies 1490:1499 innovative strategies to prevent or reverse metabolic derangements in VO-induced HF 1479:1561 innovative strategies to prevent or reverse metabolic derangements in VO-induced HF 1479:1561 These findings may provide insight into the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF. 35743252 6 59 theme gene 1049:1052 arg1 expression 1054:1063 gene expression 1049:1063 gene expression 1049:1063 The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. 35743252 7 60 theme fatty 1265:1269 arg1 oxidation 1276:1284 fatty acid oxidation 1265:1284 fatty acid oxidation 1265:1284 Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. 35743252 1 61 theme failure 245:251 arg1 development 224:234 the development 220:234 the development of heart failure (HF) 220:256 Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). 35743252 2 62 theme fistula 491:497 arg1 creation 445:452 creation 445:452 creation 445:452 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 2 62 theme fistula 491:497 arg1 closure 469:475 subsequent closure 458:475 subsequent closure 458:475 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 3 63 theme hemodynamic 692:702 arg1 studies 704:710 echocardiographic and hemodynamic studies 670:710 echocardiographic and hemodynamic studies 670:710 Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. 35743252 0 64 dep Derangements 0:11 arg1 Transcriptomics 102:116 Transcriptomics 102:116 Transcriptomics 102:116 Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses. 35743252 0 64 dep Derangements 0:11 arg1 Analyses 135:142 Metabolomics Analyses 122:142 Metabolomics Analyses 122:142 Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses. 35743252 2 65 theme energetics 378:387 arg1 reversibility 353:365 reversibility 353:365 reversibility of cardiac energetics 353:387 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35743252 2 65 theme energetics 378:387 arg1 changes 341:347 the changes 337:347 the changes 337:347 This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. 35600398 0 0 theme Preclinical 84:94 arg1 Models 96:101 Human Tumor Preclinical Models 72:101 Human Tumor Preclinical Models 72:101 Targeting a Tumor-Specific Epitope on Podocalyxin Increases Survival in Human Tumor Preclinical Models. 35600398 6 1 theme pancreatic 1174:1183 arg1 lines 1217:1221 killing ovarian, pancreatic, glioblastoma and leukemia cell lines 1157:1221 killing ovarian, pancreatic, glioblastoma and leukemia cell lines 1157:1221 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 8 2 theme tumor-specific 1428:1441 arg1 PODO447-ADCs 1400:1411 PODO447-ADCs 1400:1411 PODO447-ADCs 1400:1411 These data reveal PODO447-ADCs as exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors. 35600398 8 2 theme tumor-specific 1428:1441 arg1 reagents 1484:1491 exquisitely tumor-specific and highly efficacious immunotherapeutic reagents 1416:1491 exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors 1416:1525 These data reveal PODO447-ADCs as exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors. 35600398 1 3 theme surface 147:153 arg1 Podocalyxin 104:114 Podocalyxin 104:114 Podocalyxin (Podxl) 104:122 Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. 35600398 1 3 theme surface 147:153 arg1 sialomucin 155:164 a CD34-related cell surface sialomucin 127:164 a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion 127:295 Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. 35600398 7 4 theme NSG 1355:1357 arg1 models 1374:1379 xenografted NSG and Nude mouse models 1343:1379 xenografted NSG and Nude mouse models 1343:1379 Finally, we demonstrate PODO447-ADCs are highly effective in targeting human pancreatic and ovarian tumors in xenografted NSG and Nude mouse models. 35600398 0 5 theme Tumor 78:82 arg1 Models 96:101 Human Tumor Preclinical Models 72:101 Human Tumor Preclinical Models 72:101 Targeting a Tumor-Specific Epitope on Podocalyxin Increases Survival in Human Tumor Preclinical Models. 35600398 7 6 theme Nude 1363:1366 arg1 models 1374:1379 xenografted NSG and Nude mouse models 1343:1379 xenografted NSG and Nude mouse models 1343:1379 Finally, we demonstrate PODO447-ADCs are highly effective in targeting human pancreatic and ovarian tumors in xenografted NSG and Nude mouse models. 35600398 9 7 theme appropriate 1555:1565 arg1 characteristics 1567:1581 the appropriate characteristics 1551:1581 the appropriate characteristics for further development 1551:1605 Thus, PODO447 exhibits the appropriate characteristics for further development as a targeted clinical immunotherapy. 35600398 9 7 theme appropriate 1555:1565 arg1 immunotherapy 1630:1642 a targeted clinical immunotherapy 1610:1642 a targeted clinical immunotherapy 1610:1642 Thus, PODO447 exhibits the appropriate characteristics for further development as a targeted clinical immunotherapy. 35600398 5 8 link O-linked 908:915 arg1 glycan 924:929 an O-linked core 1 glycan 905:929 an O-linked core 1 glycan presented in the context of the Podxl peptide backbone 905:984 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 5 8 link O-linked 908:915 arg1 array 797:801 an array 794:801 an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it 794:900 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 7 9 theme mouse 1368:1372 arg1 models 1374:1379 xenografted NSG and Nude mouse models 1343:1379 xenografted NSG and Nude mouse models 1343:1379 Finally, we demonstrate PODO447-ADCs are highly effective in targeting human pancreatic and ovarian tumors in xenografted NSG and Nude mouse models. 35600398 6 10 theme ovarian 1165:1171 arg1 lines 1217:1221 killing ovarian, pancreatic, glioblastoma and leukemia cell lines 1157:1221 killing ovarian, pancreatic, glioblastoma and leukemia cell lines 1157:1221 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 6 11 theme antibody 1124:1131 arg1 PODO447 1071:1077 PODO447 1071:1077 PODO447 1071:1077 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 6 11 theme antibody 1124:1131 arg1 ADC 1149:1151 ADC 1149:1151 ADC 1149:1151 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 6 11 theme antibody 1124:1131 arg1 conjugate 1138:1146 a highly specific and effective antibody drug conjugate 1092:1146 a highly specific and effective antibody drug conjugate (ADC) 1092:1152 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 7 12 theme ovarian 1325:1331 arg1 tumors 1333:1338 human pancreatic and ovarian tumors 1304:1338 tumors 1333:1338 Finally, we demonstrate PODO447-ADCs are highly effective in targeting human pancreatic and ovarian tumors in xenografted NSG and Nude mouse models. 35600398 8 13 theme immunotherapeutic 1466:1482 arg1 PODO447-ADCs 1400:1411 PODO447-ADCs 1400:1411 PODO447-ADCs 1400:1411 These data reveal PODO447-ADCs as exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors. 35600398 8 13 theme immunotherapeutic 1466:1482 arg1 reagents 1484:1491 exquisitely tumor-specific and highly efficacious immunotherapeutic reagents 1416:1491 exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors 1416:1525 These data reveal PODO447-ADCs as exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors. 35600398 4 14 gly glycoform 694:702 arg1 Podxl 707:711 Podxl 707:711 Podxl 707:711 Recently, we developed a novel antibody, PODO447, which shows exquisite specificity for a tumor-restricted glycoform of Podxl but does not react with Podxl expressed by normal adult tissue. 35600398 6 15 theme toxic 1056:1060 arg1 payload 1062:1068 monomethyl auristatin E (MMAE) toxic payload 1025:1068 monomethyl auristatin E (MMAE) toxic payload 1025:1068 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 9 16 theme further 1587:1593 arg1 development 1595:1605 further development 1587:1605 further development 1587:1605 Thus, PODO447 exhibits the appropriate characteristics for further development as a targeted clinical immunotherapy. 35600398 5 17 used utilized 785:792 arg2 we 782:783 we 782:783 we 782:783 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 5 18 theme reactive 871:878 arg1 epitope 880:886 the PODO447 reactive epitope 859:886 the PODO447 reactive epitope 859:886 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 5 19 theme O-linked 908:915 arg1 glycan 924:929 an O-linked core 1 glycan 905:929 an O-linked core 1 glycan presented in the context of the Podxl peptide backbone 905:984 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 5 19 theme O-linked 908:915 arg1 array 797:801 an array 794:801 an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it 794:900 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 2 20 theme tumors 370:375 arg1 array 355:359 a wide array 348:359 a wide array of human tumors 348:375 Importantly, it is also frequently upregulated on a wide array of human tumors and its expression often correlates with poor prognosis. 35600398 3 21 theme key 497:499 arg1 role 501:504 a key role 495:504 a key role 495:504 We previously showed that, in xenograft studies, Podxl plays a key role in metastatic disease by making tumor initiating cells more mobile and invasive. 35600398 2 22 theme human 364:368 arg1 tumors 370:375 human tumors 364:375 human tumors 364:375 Importantly, it is also frequently upregulated on a wide array of human tumors and its expression often correlates with poor prognosis. 35600398 7 23 theme xenografted 1343:1353 arg1 models 1374:1379 xenografted NSG and Nude mouse models 1343:1379 xenografted NSG and Nude mouse models 1343:1379 Finally, we demonstrate PODO447-ADCs are highly effective in targeting human pancreatic and ovarian tumors in xenografted NSG and Nude mouse models. 35600398 8 24 theme efficacious 1454:1464 arg1 PODO447-ADCs 1400:1411 PODO447-ADCs 1400:1411 PODO447-ADCs 1400:1411 These data reveal PODO447-ADCs as exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors. 35600398 8 24 theme efficacious 1454:1464 arg1 reagents 1484:1491 exquisitely tumor-specific and highly efficacious immunotherapeutic reagents 1416:1491 exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors 1416:1525 These data reveal PODO447-ADCs as exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors. 35600398 5 25 theme glycosylation 806:818 arg1 lines 835:839 glycosylation defective cell lines 806:839 glycosylation defective cell lines 806:839 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 2 26 theme poor 418:421 arg1 prognosis 423:431 poor prognosis 418:431 poor prognosis 418:431 Importantly, it is also frequently upregulated on a wide array of human tumors and its expression often correlates with poor prognosis. 35600398 1 27 theme key 267:269 arg1 role 271:274 a key role 265:274 a key role 265:274 Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. 35600398 9 28 theme targeted 1612:1619 arg1 immunotherapy 1630:1642 a targeted clinical immunotherapy 1610:1642 a targeted clinical immunotherapy 1610:1642 Thus, PODO447 exhibits the appropriate characteristics for further development as a targeted clinical immunotherapy. 35600398 9 28 theme targeted 1612:1619 arg1 characteristics 1567:1581 the appropriate characteristics 1551:1581 the appropriate characteristics for further development 1551:1605 Thus, PODO447 exhibits the appropriate characteristics for further development as a targeted clinical immunotherapy. 35600398 4 29 theme tumor-restricted 677:692 arg1 glycoform 694:702 a tumor-restricted glycoform 675:702 a tumor-restricted glycoform of Podxl 675:711 Recently, we developed a novel antibody, PODO447, which shows exquisite specificity for a tumor-restricted glycoform of Podxl but does not react with Podxl expressed by normal adult tissue. 35600398 5 30 theme defective 820:828 arg1 lines 835:839 glycosylation defective cell lines 806:839 glycosylation defective cell lines 806:839 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 9 31 theme clinical 1621:1628 arg1 immunotherapy 1630:1642 a targeted clinical immunotherapy 1610:1642 a targeted clinical immunotherapy 1610:1642 Thus, PODO447 exhibits the appropriate characteristics for further development as a targeted clinical immunotherapy. 35600398 9 31 theme clinical 1621:1628 arg1 characteristics 1567:1581 the appropriate characteristics 1551:1581 the appropriate characteristics for further development 1551:1605 Thus, PODO447 exhibits the appropriate characteristics for further development as a targeted clinical immunotherapy. 35600398 6 32 theme effective 1114:1122 arg1 PODO447 1071:1077 PODO447 1071:1077 PODO447 1071:1077 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 6 32 theme effective 1114:1122 arg1 ADC 1149:1151 ADC 1149:1151 ADC 1149:1151 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 6 32 theme effective 1114:1122 arg1 conjugate 1138:1146 a highly specific and effective antibody drug conjugate 1092:1146 a highly specific and effective antibody drug conjugate (ADC) 1092:1152 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 3 33 theme metastatic 509:518 arg1 disease 520:526 metastatic disease 509:526 metastatic disease 509:526 We previously showed that, in xenograft studies, Podxl plays a key role in metastatic disease by making tumor initiating cells more mobile and invasive. 35600398 0 34 theme Tumor-Specific 12:25 arg1 Epitope 27:33 a Tumor-Specific Epitope 10:33 a Tumor-Specific Epitope on Podocalyxin 10:48 Targeting a Tumor-Specific Epitope on Podocalyxin Increases Survival in Human Tumor Preclinical Models. 35600398 1 35 theme CD34-related 129:140 arg1 Podocalyxin 104:114 Podocalyxin 104:114 Podocalyxin (Podxl) 104:122 Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. 35600398 1 35 theme CD34-related 129:140 arg1 sialomucin 155:164 a CD34-related cell surface sialomucin 127:164 a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion 127:295 Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. 35600398 4 36 theme exquisite 649:657 arg1 specificity 659:669 exquisite specificity 649:669 exquisite specificity for a tumor-restricted glycoform of Podxl 649:711 Recently, we developed a novel antibody, PODO447, which shows exquisite specificity for a tumor-restricted glycoform of Podxl but does not react with Podxl expressed by normal adult tissue. 35600398 4 37 theme adult 763:767 arg1 tissue 769:774 normal adult tissue 756:774 normal adult tissue 756:774 Recently, we developed a novel antibody, PODO447, which shows exquisite specificity for a tumor-restricted glycoform of Podxl but does not react with Podxl expressed by normal adult tissue. 35600398 1 38 theme adult 203:207 arg1 endothelia 218:227 adult vascular endothelia 203:227 adult vascular endothelia 203:227 Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. 35600398 4 39 theme novel 612:616 arg1 PODO447 628:634 PODO447 628:634 PODO447 628:634 Recently, we developed a novel antibody, PODO447, which shows exquisite specificity for a tumor-restricted glycoform of Podxl but does not react with Podxl expressed by normal adult tissue. 35600398 4 39 theme novel 612:616 arg1 antibody 618:625 a novel antibody 610:625 a novel antibody 610:625 Recently, we developed a novel antibody, PODO447, which shows exquisite specificity for a tumor-restricted glycoform of Podxl but does not react with Podxl expressed by normal adult tissue. 35600398 6 40 theme cell 1212:1215 arg1 lines 1217:1221 killing ovarian, pancreatic, glioblastoma and leukemia cell lines 1157:1221 killing ovarian, pancreatic, glioblastoma and leukemia cell lines 1157:1221 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 4 41 theme normal 756:761 arg1 tissue 769:774 normal adult tissue 756:774 normal adult tissue 756:774 Recently, we developed a novel antibody, PODO447, which shows exquisite specificity for a tumor-restricted glycoform of Podxl but does not react with Podxl expressed by normal adult tissue. 35600398 1 42 theme vascular 209:216 arg1 endothelia 218:227 adult vascular endothelia 203:227 adult vascular endothelia 203:227 Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. 35600398 7 43 from models 1374:1379 arg1 pancreatic 1310:1319 pancreatic 1310:1319 pancreatic 1310:1319 Finally, we demonstrate PODO447-ADCs are highly effective in targeting human pancreatic and ovarian tumors in xenografted NSG and Nude mouse models. 35600398 5 44 theme cell 830:833 arg1 lines 835:839 glycosylation defective cell lines 806:839 glycosylation defective cell lines 806:839 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 6 45 theme leukemia 1203:1210 arg1 lines 1217:1221 killing ovarian, pancreatic, glioblastoma and leukemia cell lines 1157:1221 killing ovarian, pancreatic, glioblastoma and leukemia cell lines 1157:1221 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 3 46 theme tumor 538:542 arg1 cells 555:559 tumor initiating cells 538:559 tumor initiating cells 538:559 We previously showed that, in xenograft studies, Podxl plays a key role in metastatic disease by making tumor initiating cells more mobile and invasive. 35600398 5 47 theme Podxl 963:967 arg1 backbone 977:984 the Podxl peptide backbone 959:984 the Podxl peptide backbone 959:984 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 3 48 theme initiating 544:553 arg1 cells 555:559 tumor initiating cells 538:559 tumor initiating cells 538:559 We previously showed that, in xenograft studies, Podxl plays a key role in metastatic disease by making tumor initiating cells more mobile and invasive. 35600398 3 49 theme xenograft 464:472 arg1 studies 474:480 xenograft studies 464:480 xenograft studies 464:480 We previously showed that, in xenograft studies, Podxl plays a key role in metastatic disease by making tumor initiating cells more mobile and invasive. 35600398 7 50 dep demonstrate 1245:1255 arg1 effective 1281:1289 effective 1281:1289 effective 1281:1289 Finally, we demonstrate PODO447-ADCs are highly effective in targeting human pancreatic and ovarian tumors in xenografted NSG and Nude mouse models. 35600398 6 51 theme glioblastoma 1186:1197 arg1 lines 1217:1221 killing ovarian, pancreatic, glioblastoma and leukemia cell lines 1157:1221 killing ovarian, pancreatic, glioblastoma and leukemia cell lines 1157:1221 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 5 52 theme peptide 969:975 arg1 backbone 977:984 the Podxl peptide backbone 959:984 the Podxl peptide backbone 959:984 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 6 53 theme drug 1133:1136 arg1 PODO447 1071:1077 PODO447 1071:1077 PODO447 1071:1077 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 6 53 theme drug 1133:1136 arg1 ADC 1149:1151 ADC 1149:1151 ADC 1149:1151 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 6 53 theme drug 1133:1136 arg1 conjugate 1138:1146 a highly specific and effective antibody drug conjugate 1092:1146 a highly specific and effective antibody drug conjugate (ADC) 1092:1152 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 4 54 theme Podxl 707:711 arg1 glycoform 694:702 a tumor-restricted glycoform 675:702 a tumor-restricted glycoform of Podxl 675:711 Recently, we developed a novel antibody, PODO447, which shows exquisite specificity for a tumor-restricted glycoform of Podxl but does not react with Podxl expressed by normal adult tissue. 35600398 8 55 theme tumors 1520:1525 arg1 targeting 1501:1509 the targeting 1497:1509 the targeting of human tumors 1497:1525 These data reveal PODO447-ADCs as exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors. 35600398 5 56 theme core 917:920 arg1 glycan 924:929 an O-linked core 1 glycan 905:929 an O-linked core 1 glycan presented in the context of the Podxl peptide backbone 905:984 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 5 56 theme core 917:920 arg1 array 797:801 an array 794:801 an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it 794:900 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 5 57 theme backbone 977:984 arg1 context 948:954 the context 944:954 the context of the Podxl peptide backbone 944:984 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 6 58 theme specific 1101:1108 arg1 PODO447 1071:1077 PODO447 1071:1077 PODO447 1071:1077 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 6 58 theme specific 1101:1108 arg1 ADC 1149:1151 ADC 1149:1151 ADC 1149:1151 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 6 58 theme specific 1101:1108 arg1 conjugate 1138:1146 a highly specific and effective antibody drug conjugate 1092:1146 a highly specific and effective antibody drug conjugate (ADC) 1092:1152 Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines in vitro. 35600398 5 59 theme lines 835:839 arg1 glycan 924:929 an O-linked core 1 glycan 905:929 an O-linked core 1 glycan presented in the context of the Podxl peptide backbone 905:984 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 5 59 theme lines 835:839 arg1 array 797:801 an array 794:801 an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it 794:900 Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. 35600398 8 60 theme human 1514:1518 arg1 tumors 1520:1525 human tumors 1514:1525 human tumors 1514:1525 These data reveal PODO447-ADCs as exquisitely tumor-specific and highly efficacious immunotherapeutic reagents for the targeting of human tumors. 35600398 0 61 theme Human 72:76 arg1 Models 96:101 Human Tumor Preclinical Models 72:101 Human Tumor Preclinical Models 72:101 Targeting a Tumor-Specific Epitope on Podocalyxin Increases Survival in Human Tumor Preclinical Models. 35600398 2 62 theme wide 350:353 arg1 array 355:359 a wide array 348:359 a wide array of human tumors 348:375 Importantly, it is also frequently upregulated on a wide array of human tumors and its expression often correlates with poor prognosis. 35600398 1 63 theme kidney 233:238 arg1 podocytes 240:248 kidney podocytes 233:248 kidney podocytes where it plays a key role in blocking adhesion 233:295 Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. 35600398 0 64 from Epitope 27:33 arg1 Podocalyxin 38:48 Podocalyxin 38:48 Podocalyxin 38:48 Targeting a Tumor-Specific Epitope on Podocalyxin Increases Survival in Human Tumor Preclinical Models. 35600398 1 65 theme cell 142:145 arg1 Podocalyxin 104:114 Podocalyxin 104:114 Podocalyxin (Podxl) 104:122 Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. 35600398 1 65 theme cell 142:145 arg1 sialomucin 155:164 a CD34-related cell surface sialomucin 127:164 a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion 127:295 Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. 35600398 7 66 from pancreatic 1310:1319 arg1 models 1374:1379 xenografted NSG and Nude mouse models 1343:1379 xenografted NSG and Nude mouse models 1343:1379 Finally, we demonstrate PODO447-ADCs are highly effective in targeting human pancreatic and ovarian tumors in xenografted NSG and Nude mouse models. 36975134 0 0 from Transfer 17:24 arg1 Heterodimer 50:60 a Rylene Imide-Based Heterodimer 29:60 a Rylene Imide-Based Heterodimer 29:60 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 36975134 4 1 theme upper 713:717 arg1 levels 738:743 upper vibrational energy levels 713:743 upper vibrational energy levels of the singlet states 713:765 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 1 2 theme simplified 153:162 arg1 structures 164:173 simplified structures 153:173 simplified structures 153:173 The development of antenna molecules with simplified structures can effectively avoid the complex exciton dynamics resulting from conformational mobility. 36975134 4 3 theme absorption 608:617 arg1 spectroscopy 619:630 transient absorption spectroscopy 598:630 transient absorption spectroscopy 598:630 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 5 4 theme ultrafast 876:884 arg1 transfer 904:911 ultrafast excitation energy transfer 876:911 ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor 876:982 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 3 5 link bay-to-bay-linked 465:481 arg1 TP 483:484 the bay-to-bay-linked TP 461:484 the bay-to-bay-linked TP 461:484 Tuned by varying functionalization positions, the bay-to-bay-linked TP offers a strong chromophore coupling, while the bay-to-N-linked TBP exhibits a weak chromophore coupling. 36975134 4 6 theme transient 598:606 arg1 spectroscopy 619:630 transient absorption spectroscopy 598:630 transient absorption spectroscopy 598:630 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 0 7 theme Electronic 90:99 arg1 Coupling 101:108 Intramolecular Electronic Coupling 75:108 Intramolecular Electronic Coupling 75:108 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 36975134 6 8 theme capable 1120:1126 arg1 molecules 1110:1118 novel small molecules 1098:1118 novel small molecules capable of efficient energy transfer 1098:1155 This result provides insight into designing novel small molecules capable of efficient energy transfer. 36975134 1 9 with molecules 138:146 arg1 structures 164:173 simplified structures 153:173 simplified structures 153:173 The development of antenna molecules with simplified structures can effectively avoid the complex exciton dynamics resulting from conformational mobility. 36975134 6 10 theme energy 1141:1146 arg1 transfer 1148:1155 efficient energy transfer 1131:1155 efficient energy transfer 1131:1155 This result provides insight into designing novel small molecules capable of efficient energy transfer. 36975134 6 11 theme novel 1098:1102 arg1 molecules 1110:1118 novel small molecules 1098:1118 novel small molecules capable of efficient energy transfer 1098:1155 This result provides insight into designing novel small molecules capable of efficient energy transfer. 36975134 0 12 theme Intramolecular 75:88 arg1 Coupling 101:108 Intramolecular Electronic Coupling 75:108 Intramolecular Electronic Coupling 75:108 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 36975134 5 13 theme transfer 1011:1018 arg1 process 1025:1031 the subsequent charge transfer (CT) process 989:1031 the subsequent charge transfer (CT) process 989:1031 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 5 14 dep = 924:924 arg1 EET 914:916 EET 914:916 EET 914:916 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 3 15 theme weak 565:568 arg1 coupling 582:589 a weak chromophore coupling 563:589 a weak chromophore coupling 563:589 Tuned by varying functionalization positions, the bay-to-bay-linked TP offers a strong chromophore coupling, while the bay-to-N-linked TBP exhibits a weak chromophore coupling. 36975134 5 16 dep transfer 904:911 arg1 = 924:924 = 924:924 = 924:924 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 3 17 theme strong 495:500 arg1 coupling 514:521 a strong chromophore coupling 493:521 a strong chromophore coupling 493:521 Tuned by varying functionalization positions, the bay-to-bay-linked TP offers a strong chromophore coupling, while the bay-to-N-linked TBP exhibits a weak chromophore coupling. 36975134 4 18 theme energy 731:736 arg1 levels 738:743 upper vibrational energy levels 713:743 upper vibrational energy levels of the singlet states 713:765 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 4 19 theme τVR 694:696 arg1 fs 704:705 τVR < 400 fs 694:705 τVR < 400 fs 694:705 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 4 19 theme τVR 694:696 arg1 relaxation 682:691 ultrafast vibrational relaxation 660:691 ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states 660:765 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 0 20 theme Coupling 101:108 arg1 Role 67:70 The Role 63:70 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 0:109 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 36975134 5 21 theme CT 1021:1022 arg1 process 1025:1031 the subsequent charge transfer (CT) process 989:1031 the subsequent charge transfer (CT) process 989:1031 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 4 22 dep = 835:835 arg1 ET 827:828 ET 827:828 ET 827:828 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 0 23 theme Energy 10:15 arg1 Transfer 17:24 Efficient Energy Transfer 0:24 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 0:109 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 36975134 4 24 theme singlet 752:758 arg1 states 760:765 the singlet states 748:765 the singlet states 748:765 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 2 25 theme energy 384:389 arg1 sink 391:394 an energy sink 381:394 an energy sink 381:394 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink were investigated. 36975134 0 26 theme Efficient 0:8 arg1 Transfer 17:24 Efficient Energy Transfer 0:24 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 0:109 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 36975134 2 27 dep heterodimers 279:290 arg1 heterodimers 279:290 Two distinct heterodimers 266:290 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink 266:394 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink were investigated. 36975134 2 27 dep heterodimers 279:290 arg1 TBP 299:301 TBP 299:301 TBP 299:301 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink were investigated. 36975134 2 27 dep heterodimers 279:290 arg1 TP 292:293 TP 292:293 TP 292:293 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink were investigated. 36975134 5 28 theme energy 897:902 arg1 transfer 904:911 ultrafast excitation energy transfer 876:911 ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor 876:982 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 3 29 theme chromophore 570:580 arg1 coupling 582:589 a weak chromophore coupling 563:589 a weak chromophore coupling 563:589 Tuned by varying functionalization positions, the bay-to-bay-linked TP offers a strong chromophore coupling, while the bay-to-N-linked TBP exhibits a weak chromophore coupling. 36975134 5 30 from donor 962:966 arg1 transfer 904:911 ultrafast excitation energy transfer 876:911 ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor 876:982 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 1 31 theme complex 201:207 arg1 dynamics 217:224 the complex exciton dynamics 197:224 the complex exciton dynamics resulting from conformational mobility 197:263 The development of antenna molecules with simplified structures can effectively avoid the complex exciton dynamics resulting from conformational mobility. 36975134 4 32 theme states 760:765 arg1 levels 738:743 upper vibrational energy levels 713:743 upper vibrational energy levels of the singlet states 713:765 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 1 33 theme exciton 209:215 arg1 dynamics 217:224 the complex exciton dynamics 197:224 the complex exciton dynamics resulting from conformational mobility 197:263 The development of antenna molecules with simplified structures can effectively avoid the complex exciton dynamics resulting from conformational mobility. 36975134 0 34 theme Rylene 31:36 arg1 Heterodimer 50:60 a Rylene Imide-Based Heterodimer 29:60 a Rylene Imide-Based Heterodimer 29:60 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 36975134 4 35 theme vibrational 719:729 arg1 levels 738:743 upper vibrational energy levels 713:743 upper vibrational energy levels of the singlet states 713:765 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 3 36 theme functionalization 432:448 arg1 positions 450:458 functionalization positions 432:458 functionalization positions 432:458 Tuned by varying functionalization positions, the bay-to-bay-linked TP offers a strong chromophore coupling, while the bay-to-N-linked TBP exhibits a weak chromophore coupling. 36975134 4 37 dep transfer 817:824 arg1 = 835:835 = 835:835 = 835:835 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 3 38 link bay-to-N-linked 534:548 arg1 TBP 550:552 the bay-to-N-linked TBP 530:552 the bay-to-N-linked TBP 530:552 Tuned by varying functionalization positions, the bay-to-bay-linked TP offers a strong chromophore coupling, while the bay-to-N-linked TBP exhibits a weak chromophore coupling. 36975134 5 39 theme subsequent 993:1002 arg1 process 1025:1031 the subsequent charge transfer (CT) process 989:1031 the subsequent charge transfer (CT) process 989:1031 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 4 40 theme electron 808:815 arg1 transfer 817:824 electron transfer 808:824 electron transfer (ET, τET = 2.5 ps) from TDI to PDI 808:859 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 3 41 theme bay-to-bay-linked 465:481 arg1 TP 483:484 the bay-to-bay-linked TP 461:484 the bay-to-bay-linked TP 461:484 Tuned by varying functionalization positions, the bay-to-bay-linked TP offers a strong chromophore coupling, while the bay-to-N-linked TBP exhibits a weak chromophore coupling. 36975134 5 42 theme charge 1004:1009 arg1 process 1025:1031 the subsequent charge transfer (CT) process 989:1031 the subsequent charge transfer (CT) process 989:1031 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 5 43 theme PDI 958:960 arg1 donor 962:966 the excited PDI donor 946:966 the excited PDI donor to TDI acceptor 946:982 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 3 44 theme chromophore 502:512 arg1 coupling 514:521 a strong chromophore coupling 493:521 a strong chromophore coupling 493:521 Tuned by varying functionalization positions, the bay-to-bay-linked TP offers a strong chromophore coupling, while the bay-to-N-linked TBP exhibits a weak chromophore coupling. 36975134 0 45 theme Imide-Based 38:48 arg1 Heterodimer 50:60 a Rylene Imide-Based Heterodimer 29:60 a Rylene Imide-Based Heterodimer 29:60 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 36975134 6 46 theme transfer 1148:1155 arg1 capable 1120:1126 capable 1120:1126 capable 1120:1126 This result provides insight into designing novel small molecules capable of efficient energy transfer. 36975134 5 47 theme TDI 971:973 arg1 acceptor 975:982 TDI acceptor 971:982 TDI acceptor 971:982 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 2 48 dep perylenediimide 316:330 arg1 terrylenediimide 348:363 terrylenediimide 348:363 terrylenediimide 348:363 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink were investigated. 36975134 2 48 dep perylenediimide 316:330 arg1 donor 338:342 donor 338:342 donor 338:342 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink were investigated. 36975134 2 48 dep perylenediimide 316:330 arg1 TDI 366:368 TDI 366:368 TDI 366:368 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink were investigated. 36975134 6 49 theme efficient 1131:1139 arg1 transfer 1148:1155 efficient energy transfer 1131:1155 efficient energy transfer 1131:1155 This result provides insight into designing novel small molecules capable of efficient energy transfer. 36975134 4 50 theme < 698:698 arg1 fs 704:705 τVR < 400 fs 694:705 τVR < 400 fs 694:705 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 4 50 theme < 698:698 arg1 relaxation 682:691 ultrafast vibrational relaxation 660:691 ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states 660:765 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 5 51 theme excited 950:956 arg1 donor 962:966 the excited PDI donor 946:966 the excited PDI donor to TDI acceptor 946:982 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 5 52 theme excitation 886:895 arg1 transfer 904:911 ultrafast excitation energy transfer 876:911 ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor 876:982 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 4 53 from levels 738:743 arg1 fs 704:705 τVR < 400 fs 694:705 τVR < 400 fs 694:705 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 4 53 from levels 738:743 arg1 relaxation 682:691 ultrafast vibrational relaxation 660:691 ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states 660:765 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 5 54 theme ± 931:931 arg1 ps 937:938 0.48 ± 0.1 ps 926:938 0.48 ± 0.1 ps 926:938 TBP exhibited ultrafast excitation energy transfer (EET, τEET = 0.48 ± 0.1 ps) from the excited PDI donor to TDI acceptor, and the subsequent charge transfer (CT) process was almost quenched. 36975134 0 55 dep Transfer 17:24 arg1 Role 67:70 The Role 63:70 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 0:109 Efficient Energy Transfer in a Rylene Imide-Based Heterodimer: The Role of Intramolecular Electronic Coupling. 36975134 1 56 theme antenna 130:136 arg1 molecules 138:146 antenna molecules 130:146 antenna molecules with simplified structures 130:173 The development of antenna molecules with simplified structures can effectively avoid the complex exciton dynamics resulting from conformational mobility. 36975134 1 57 theme conformational 241:254 arg1 mobility 256:263 conformational mobility 241:263 conformational mobility 241:263 The development of antenna molecules with simplified structures can effectively avoid the complex exciton dynamics resulting from conformational mobility. 36975134 4 58 theme vibrational 670:680 arg1 fs 704:705 τVR < 400 fs 694:705 τVR < 400 fs 694:705 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 4 58 theme vibrational 670:680 arg1 relaxation 682:691 ultrafast vibrational relaxation 660:691 ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states 660:765 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 2 59 theme distinct 270:277 arg1 heterodimers 279:290 Two distinct heterodimers 266:290 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink 266:394 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink were investigated. 36975134 2 59 theme distinct 270:277 arg1 TBP 299:301 TBP 299:301 TBP 299:301 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink were investigated. 36975134 2 59 theme distinct 270:277 arg1 TP 292:293 TP 292:293 TP 292:293 Two distinct heterodimers TP and TBP comprising a perylenediimide (PDI) donor and terrylenediimide (TDI) acting as an energy sink were investigated. 36975134 4 60 theme ultrafast 660:668 arg1 fs 704:705 τVR < 400 fs 694:705 τVR < 400 fs 694:705 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 4 60 theme ultrafast 660:668 arg1 relaxation 682:691 ultrafast vibrational relaxation 660:691 ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states 660:765 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 1 61 theme molecules 138:146 arg1 development 115:125 The development 111:125 The development of antenna molecules with simplified structures 111:173 The development of antenna molecules with simplified structures can effectively avoid the complex exciton dynamics resulting from conformational mobility. 36975134 4 62 from TDI 850:852 arg1 transfer 817:824 electron transfer 808:824 electron transfer (ET, τET = 2.5 ps) from TDI to PDI 808:859 Using transient absorption spectroscopy, we found that TP underwent ultrafast vibrational relaxation (τVR < 400 fs) from upper vibrational energy levels of the singlet states after pumping at 490 nm, and followed by electron transfer (ET, τET = 2.5 ps) from TDI to PDI. 36975134 6 63 theme small 1104:1108 arg1 molecules 1110:1118 novel small molecules 1098:1118 novel small molecules capable of efficient energy transfer 1098:1155 This result provides insight into designing novel small molecules capable of efficient energy transfer. 36975134 3 64 theme bay-to-N-linked 534:548 arg1 TBP 550:552 the bay-to-N-linked TBP 530:552 the bay-to-N-linked TBP 530:552 Tuned by varying functionalization positions, the bay-to-bay-linked TP offers a strong chromophore coupling, while the bay-to-N-linked TBP exhibits a weak chromophore coupling. 36920703 4 0 used used 437:440 arg2 tool 447:450 a tool 445:450 a tool in the study of mammarenaviruses 445:483 Pseudotyped viruses have been widely used as a tool in the study of mammarenaviruses. 36920703 4 0 used used 437:440 arg2 viruses 412:418 Pseudotyped viruses 400:418 Pseudotyped viruses 400:418 Pseudotyped viruses have been widely used as a tool in the study of mammarenaviruses. 36920703 4 1 theme mammarenaviruses 468:483 arg1 study 459:463 the study 455:463 the study of mammarenaviruses 455:483 Pseudotyped viruses have been widely used as a tool in the study of mammarenaviruses. 36920703 5 2 theme lentiviral 508:517 arg1 vectors 557:563 MLV-based vectors 547:563 MLV-based vectors 547:563 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 5 2 theme lentiviral 508:517 arg1 vectors 519:525 FIV-based lentiviral vectors 498:525 FIV-based lentiviral vectors 498:525 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 5 2 theme lentiviral 508:517 arg1 vectors 538:544 VSV-based vectors 528:544 VSV-based vectors 528:544 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 6 3 theme mechanisms 913:922 arg1 detection 759:767 neutralizing antibody detection 737:767 neutralizing antibody detection 737:767 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 3 theme mechanisms 913:922 arg1 studies 807:813 viral virulence studies 791:813 viral virulence studies 791:813 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 3 theme mechanisms 913:922 arg1 research 727:734 receptor research 718:734 receptor research 718:734 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 3 theme mechanisms 913:922 arg1 analysis 827:834 functional analysis 816:834 functional analysis of N-linked glycans 816:854 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 3 theme mechanisms 913:922 arg1 studies 861:867 studies 861:867 studies of viral infection, endocytosis, and fusion mechanisms 861:922 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 3 theme mechanisms 913:922 arg1 screening 780:788 inhibitor screening 770:788 inhibitor screening 770:788 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 4 theme fusion 906:911 arg1 mechanisms 913:922 fusion mechanisms 906:922 fusion mechanisms 906:922 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 5 theme N-linked 839:846 arg1 glycans 848:854 N-linked glycans 839:854 N-linked glycans 839:854 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 6 theme viral 791:795 arg1 studies 807:813 viral virulence studies 791:813 viral virulence studies 791:813 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 5 7 theme reverse 570:576 arg1 approaches 586:595 reverse genetic approaches 570:595 reverse genetic approaches 570:595 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 6 8 theme receptor 718:725 arg1 research 727:734 receptor research 718:734 receptor research 718:734 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 5 9 theme pseudotyped 638:648 arg1 mammarenaviruses 650:665 pseudotyped mammarenaviruses 638:665 pseudotyped mammarenaviruses 638:665 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 4 10 theme Pseudotyped 400:410 arg1 viruses 412:418 Pseudotyped viruses 400:418 Pseudotyped viruses 400:418 Pseudotyped viruses have been widely used as a tool in the study of mammarenaviruses. 36920703 4 10 theme Pseudotyped 400:410 arg1 tool 447:450 a tool 445:450 a tool in the study of mammarenaviruses 445:483 Pseudotyped viruses have been widely used as a tool in the study of mammarenaviruses. 36920703 1 11 theme New 77:79 arg1 NW 101:102 NW 101:102 NW 101:102 Mammarenaviruses are classified into New World arenaviruses (NW) and Old World arenaviruses (OW). 36920703 1 11 theme New 77:79 arg1 arenaviruses 87:98 New World arenaviruses 77:98 New World arenaviruses (NW) 77:103 Mammarenaviruses are classified into New World arenaviruses (NW) and Old World arenaviruses (OW). 36920703 5 12 theme genetic 578:584 arg1 approaches 586:595 reverse genetic approaches 570:595 reverse genetic approaches 570:595 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 6 13 theme endocytosis 889:899 arg1 detection 759:767 neutralizing antibody detection 737:767 neutralizing antibody detection 737:767 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 13 theme endocytosis 889:899 arg1 studies 807:813 viral virulence studies 791:813 viral virulence studies 791:813 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 13 theme endocytosis 889:899 arg1 research 727:734 receptor research 718:734 receptor research 718:734 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 13 theme endocytosis 889:899 arg1 analysis 827:834 functional analysis 816:834 functional analysis of N-linked glycans 816:854 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 13 theme endocytosis 889:899 arg1 studies 861:867 studies 861:867 studies of viral infection, endocytosis, and fusion mechanisms 861:922 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 13 theme endocytosis 889:899 arg1 screening 780:788 inhibitor screening 770:788 inhibitor screening 770:788 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 1 14 theme World 81:85 arg1 NW 101:102 NW 101:102 NW 101:102 Mammarenaviruses are classified into New World arenaviruses (NW) and Old World arenaviruses (OW). 36920703 1 14 theme World 81:85 arg1 arenaviruses 87:98 New World arenaviruses 77:98 New World arenaviruses (NW) 77:103 Mammarenaviruses are classified into New World arenaviruses (NW) and Old World arenaviruses (OW). 36920703 6 15 theme virulence 797:805 arg1 studies 807:813 viral virulence studies 791:813 viral virulence studies 791:813 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 2 16 theme Lassa 266:270 arg1 LASV 279:282 LASV 279:282 LASV 279:282 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 2 16 theme Lassa 266:270 arg1 virus 272:276 the highly lethal Lassa virus 248:276 the highly lethal Lassa virus (LASV) 248:283 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 6 17 theme infection 878:886 arg1 detection 759:767 neutralizing antibody detection 737:767 neutralizing antibody detection 737:767 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 17 theme infection 878:886 arg1 studies 807:813 viral virulence studies 791:813 viral virulence studies 791:813 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 17 theme infection 878:886 arg1 research 727:734 receptor research 718:734 receptor research 718:734 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 17 theme infection 878:886 arg1 analysis 827:834 functional analysis 816:834 functional analysis of N-linked glycans 816:854 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 17 theme infection 878:886 arg1 studies 861:867 studies 861:867 studies of viral infection, endocytosis, and fusion mechanisms 861:922 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 17 theme infection 878:886 arg1 screening 780:788 inhibitor screening 770:788 inhibitor screening 770:788 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 5 18 theme MLV-based 547:555 arg1 vectors 557:563 MLV-based vectors 547:563 MLV-based vectors 547:563 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 5 18 theme MLV-based 547:555 arg1 vectors 519:525 FIV-based lentiviral vectors 498:525 FIV-based lentiviral vectors 498:525 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 0 19 theme Pseudotyped 0:10 arg1 Viruses 12:18 Pseudotyped Viruses 0:18 Pseudotyped Viruses for Mammarenavirus. 0:38 Pseudotyped Viruses for Mammarenavirus. 36920703 6 20 theme functional 816:825 arg1 analysis 827:834 functional analysis 816:834 functional analysis of N-linked glycans 816:854 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 3 21 theme severe 353:358 arg1 infections 366:375 severe acute infections 353:375 severe acute infections 353:375 Mammarenaviruses are transmitted to human by rodents, resulting in severe acute infections and hemorrhagic fever. 36920703 4 22 from tool 447:450 arg1 study 459:463 the study 455:463 the study of mammarenaviruses 455:483 Pseudotyped viruses have been widely used as a tool in the study of mammarenaviruses. 36920703 6 23 used used 710:713 arg2 mammarenaviruses 680:695 Pseudotyped mammarenaviruses 668:695 Pseudotyped mammarenaviruses 668:695 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 24 theme Pseudotyped 668:678 arg1 mammarenaviruses 680:695 Pseudotyped mammarenaviruses 668:695 Pseudotyped mammarenaviruses 668:695 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 3 25 theme acute 360:364 arg1 infections 366:375 severe acute infections 353:375 severe acute infections 353:375 Mammarenaviruses are transmitted to human by rodents, resulting in severe acute infections and hemorrhagic fever. 36920703 6 26 theme viral 872:876 arg1 infection 878:886 viral infection 872:886 viral infection 872:886 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 27 theme inhibitor 770:778 arg1 screening 780:788 inhibitor screening 770:788 inhibitor screening 770:788 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 3 28 theme hemorrhagic 381:391 arg1 fever 393:397 hemorrhagic fever 381:397 hemorrhagic fever 381:397 Mammarenaviruses are transmitted to human by rodents, resulting in severe acute infections and hemorrhagic fever. 36920703 5 29 theme mammarenaviruses 650:665 arg1 construction 622:633 the construction 618:633 the construction of pseudotyped mammarenaviruses 618:665 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 2 30 theme OW 142:143 arg1 arenaviruses 145:156 The OW arenaviruses 138:156 The OW arenaviruses 138:156 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 1 31 theme Old 109:111 arg1 arenaviruses 119:130 Old World arenaviruses 109:130 Old World arenaviruses (OW) 109:135 Mammarenaviruses are classified into New World arenaviruses (NW) and Old World arenaviruses (OW). 36920703 1 31 theme Old 109:111 arg1 OW 133:134 OW 133:134 OW 133:134 Mammarenaviruses are classified into New World arenaviruses (NW) and Old World arenaviruses (OW). 36920703 2 32 theme choriomeningitis 214:229 arg1 LCMV 238:241 LCMV 238:241 LCMV 238:241 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 2 32 theme choriomeningitis 214:229 arg1 virus 231:235 the first discovered mammarenavirus-lymphocytic choriomeningitis virus 166:235 the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) 166:242 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 6 33 theme glycans 848:854 arg1 detection 759:767 neutralizing antibody detection 737:767 neutralizing antibody detection 737:767 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 33 theme glycans 848:854 arg1 studies 807:813 viral virulence studies 791:813 viral virulence studies 791:813 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 33 theme glycans 848:854 arg1 research 727:734 receptor research 718:734 receptor research 718:734 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 33 theme glycans 848:854 arg1 analysis 827:834 functional analysis 816:834 functional analysis of N-linked glycans 816:854 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 33 theme glycans 848:854 arg1 studies 861:867 studies 861:867 studies of viral infection, endocytosis, and fusion mechanisms 861:922 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 33 theme glycans 848:854 arg1 screening 780:788 inhibitor screening 770:788 inhibitor screening 770:788 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 5 34 theme VSV-based 528:536 arg1 vectors 519:525 FIV-based lentiviral vectors 498:525 FIV-based lentiviral vectors 498:525 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 5 34 theme VSV-based 528:536 arg1 vectors 538:544 VSV-based vectors 528:544 VSV-based vectors 528:544 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 1 35 theme World 113:117 arg1 arenaviruses 119:130 Old World arenaviruses 109:130 Old World arenaviruses (OW) 109:135 Mammarenaviruses are classified into New World arenaviruses (NW) and Old World arenaviruses (OW). 36920703 1 35 theme World 113:117 arg1 OW 133:134 OW 133:134 OW 133:134 Mammarenaviruses are classified into New World arenaviruses (NW) and Old World arenaviruses (OW). 36920703 2 36 theme mammarenavirus-lymphocytic 187:212 arg1 LCMV 238:241 LCMV 238:241 LCMV 238:241 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 2 36 theme mammarenavirus-lymphocytic 187:212 arg1 virus 231:235 the first discovered mammarenavirus-lymphocytic choriomeningitis virus 166:235 the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) 166:242 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 2 37 theme lethal 259:264 arg1 LASV 279:282 LASV 279:282 LASV 279:282 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 2 37 theme lethal 259:264 arg1 virus 272:276 the highly lethal Lassa virus 248:276 the highly lethal Lassa virus (LASV) 248:283 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 6 38 theme antibody 750:757 arg1 detection 759:767 neutralizing antibody detection 737:767 neutralizing antibody detection 737:767 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 2 39 theme discovered 176:185 arg1 LCMV 238:241 LCMV 238:241 LCMV 238:241 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 2 39 theme discovered 176:185 arg1 virus 231:235 the first discovered mammarenavirus-lymphocytic choriomeningitis virus 166:235 the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) 166:242 The OW arenaviruses include the first discovered mammarenavirus-lymphocytic choriomeningitis virus (LCMV) and the highly lethal Lassa virus (LASV). 36920703 6 40 theme neutralizing 737:748 arg1 detection 759:767 neutralizing antibody detection 737:767 neutralizing antibody detection 737:767 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 6 41 link N-linked 839:846 arg1 glycans 848:854 N-linked glycans 839:854 N-linked glycans 839:854 Pseudotyped mammarenaviruses are commonly used in receptor research, neutralizing antibody detection, inhibitor screening, viral virulence studies, functional analysis of N-linked glycans, and studies of viral infection, endocytosis, and fusion mechanisms. 36920703 5 42 theme FIV-based 498:506 arg1 vectors 557:563 MLV-based vectors 547:563 MLV-based vectors 547:563 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 5 42 theme FIV-based 498:506 arg1 vectors 519:525 FIV-based lentiviral vectors 498:525 FIV-based lentiviral vectors 498:525 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 36920703 5 42 theme FIV-based 498:506 arg1 vectors 538:544 VSV-based vectors 528:544 VSV-based vectors 528:544 HIV-1, SIV, FIV-based lentiviral vectors, VSV-based vectors, MLV-based vectors, and reverse genetic approaches have been applied in the construction of pseudotyped mammarenaviruses. 35211808 13 0 theme local 1977:1981 arg1 activity 1983:1990 local activity 1977:1990 local activity 1977:1990 Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG. 35211808 2 1 theme peptide 343:349 arg1 precursor 351:359 the IGF-1 receptor (IGF-1R) peptide precursor 315:359 the IGF-1 receptor (IGF-1R) peptide precursor 315:359 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. 35211808 10 2 theme stress 1551:1556 arg1 genes 1558:1562 Endoplasmic Reticulum (ER) stress genes 1524:1562 Endoplasmic Reticulum (ER) stress genes 1524:1562 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35211808 5 3 theme different 702:710 arg1 n = 7 727:731 n = 7 727:731 n = 7 727:731 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 3 theme different 702:710 arg1 [PMM2-CDG 716:724 different CDG [PMM2-CDG 702:724 different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1) 702:787 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 9 4 theme decreased 1411:1419 arg1 phosphorylation 1428:1442 decreased ERK1/2 phosphorylation 1411:1442 decreased ERK1/2 phosphorylation 1411:1442 IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. 35211808 5 5 gly glycosylation 807:819 arg1 proIGF-1Ea 836:845 the proIGF-1Ea 832:845 the proIGF-1Ea 832:845 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 12 6 theme link 1758:1761 arg1 evidence 1737:1744 new evidence 1733:1744 new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components 1733:1862 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 11 7 theme ER-stress-related 1623:1639 arg1 expression 1646:1655 ER-stress-related gene expression 1623:1655 ER-stress-related gene expression 1623:1655 ER-stress-related gene expression negatively correlated with fibroblasts IGF-1 secretion. 35211808 7 8 theme serum 1081:1085 arg1 concentration 1087:1099 Lower IGF-1 serum concentration 1069:1099 Lower IGF-1 serum concentration 1069:1099 Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. 35211808 13 9 theme systemic 1945:1952 arg1 availability 1960:1971 reduced systemic IGF-1 availability 1937:1971 reduced systemic IGF-1 availability 1937:1971 Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG. 35211808 2 10 theme IGF-1Ea 279:285 arg1 proIGF-1Ea 299:308 proIGF-1Ea 299:308 proIGF-1Ea 299:308 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. 35211808 2 10 theme IGF-1Ea 279:285 arg1 prohormone 287:296 the IGF-1Ea prohormone 275:296 the IGF-1Ea prohormone (proIGF-1Ea) 275:309 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. 35211808 5 11 theme proIGF-1Ea 836:845 arg1 pattern 821:827 the glycosylation pattern 803:827 the glycosylation pattern of the proIGF-1Ea 803:845 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 11 theme proIGF-1Ea 836:845 arg1 activity 896:903 IGF-1R signaling activity 879:903 IGF-1R signaling activity 879:903 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 11 theme proIGF-1Ea 836:845 arg1 efficiency 864:873 IGF-1 secretion efficiency 848:873 IGF-1 secretion efficiency 848:873 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 8 12 theme IGF-1R 1223:1228 arg1 level 1241:1245 reduced IGF-1R expression level 1215:1245 reduced IGF-1R expression level 1215:1245 Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. 35211808 7 13 theme Lower 1069:1073 arg1 concentration 1087:1099 Lower IGF-1 serum concentration 1069:1099 Lower IGF-1 serum concentration 1069:1099 Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. 35211808 13 14 theme availability 1960:1971 arg1 consequences 1921:1932 the clinical consequences 1908:1932 the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG 1908:2011 Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG. 35211808 5 15 theme IGF-1 848:852 arg1 efficiency 864:873 IGF-1 secretion efficiency 848:873 IGF-1 secretion efficiency 848:873 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 6 16 theme PMM2-CDG 945:952 arg1 fibroblasts 954:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts 906:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts 906:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). 35211808 7 17 with patients 1148:1155 arg1 PMM2-CDG 1162:1169 PMM2-CDG 1162:1169 PMM2-CDG 1162:1169 Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. 35211808 5 18 theme glycosylation 807:819 arg1 pattern 821:827 the glycosylation pattern 803:827 the glycosylation pattern of the proIGF-1Ea 803:845 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 10 19 theme ER 1599:1600 arg1 stress 1602:1607 mild ER stress 1594:1607 mild ER stress in CDG cells 1594:1620 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35211808 1 20 theme growth 225:230 arg1 regulation 211:220 the regulation 207:220 the regulation of growth and development 207:246 The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. 35211808 1 21 theme insulin-like 137:148 arg1 IGF-1 167:171 IGF-1 167:171 IGF-1 167:171 The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. 35211808 1 21 theme insulin-like 137:148 arg1 factor-1 157:164 insulin-like growth factor-1 137:164 The insulin-like growth factor-1 (IGF-1) signaling pathway 133:190 The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. 35211808 1 22 theme factor-1 157:164 arg1 crucial 195:201 crucial 195:201 crucial 195:201 The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. 35211808 1 22 theme factor-1 157:164 arg1 pathway 184:190 The insulin-like growth factor-1 (IGF-1) signaling pathway 133:190 The insulin-like growth factor-1 (IGF-1) signaling pathway 133:190 The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. 35211808 6 23 theme lower 1013:1017 arg1 secretion 1025:1033 lower IGF-1 secretion 1013:1033 lower IGF-1 secretion 1013:1033 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). 35211808 13 24 theme reduced 1937:1943 arg1 availability 1960:1971 reduced systemic IGF-1 availability 1937:1971 reduced systemic IGF-1 availability 1937:1971 Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG. 35211808 0 25 theme signaling 70:78 arg1 activation 80:89 reduced IGF-1 receptor signaling activation 47:89 reduced IGF-1 receptor signaling activation 47:89 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 2 26 theme correct 253:259 arg1 processing 261:270 The correct processing 249:270 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor 249:359 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. 35211808 6 27 theme proIGF-1Ea 998:1007 arg1 secretion 1025:1033 lower IGF-1 secretion 1013:1033 lower IGF-1 secretion 1013:1033 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). 35211808 6 27 theme proIGF-1Ea 998:1007 arg1 hypoglycosylation 973:989 hypoglycosylation 973:989 hypoglycosylation of the proIGF-1Ea 973:1007 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). 35211808 8 28 theme PMM2-CDG 1294:1301 arg1 fibroblasts 1303:1313 some PMM2-CDG fibroblasts 1289:1313 some PMM2-CDG fibroblasts 1289:1313 Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. 35211808 7 29 located observed 1105:1112 arg1 ALG8-CDG 1127:1134 ALG8-CDG 1127:1134 ALG8-CDG 1127:1134 Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. 35211808 7 29 located observed 1105:1112 arg1 ALG3-CDG 1117:1124 ALG3-CDG 1117:1124 ALG3-CDG 1117:1124 Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. 35211808 7 29 located observed 1105:1112 arg2 concentration 1087:1099 Lower IGF-1 serum concentration 1069:1099 Lower IGF-1 serum concentration 1069:1099 Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. 35211808 1 30 theme signaling 174:182 arg1 crucial 195:201 crucial 195:201 crucial 195:201 The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. 35211808 1 30 theme signaling 174:182 arg1 pathway 184:190 The insulin-like growth factor-1 (IGF-1) signaling pathway 133:190 The insulin-like growth factor-1 (IGF-1) signaling pathway 133:190 The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. 35211808 13 31 theme Further 1865:1871 arg1 studies 1873:1879 Further studies 1865:1879 Further studies 1865:1879 Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG. 35211808 3 32 theme heterogeneous 454:466 arg1 group 468:472 a clinically heterogeneous group 441:472 a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG) 441:545 Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). 35211808 3 32 theme heterogeneous 454:466 arg1 diseases 487:494 inherited diseases 477:494 inherited diseases called Congenital Disorders of Glycosylation (CDG) 477:545 Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). 35211808 0 33 theme glycosylation 118:130 arg1 disorders 105:113 congenital disorders 94:113 congenital disorders of glycosylation 94:130 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 10 34 theme CDG 1612:1614 arg1 cells 1616:1620 CDG cells 1612:1620 CDG cells 1612:1620 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35211808 0 35 theme Defective 0:8 arg1 N-glycosylation 27:41 Defective IGF-1 prohormone N-glycosylation 0:41 Defective IGF-1 prohormone N-glycosylation 0:41 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 8 36 located observed 1251:1258 arg2 level 1241:1245 reduced IGF-1R expression level 1215:1245 reduced IGF-1R expression level 1215:1245 Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. 35211808 8 36 located observed 1251:1258 arg1 ALG8-CDG 1273:1280 ALG8-CDG 1273:1280 ALG8-CDG 1273:1280 Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. 35211808 8 36 located observed 1251:1258 arg1 ALG3-CDG 1263:1270 ALG3-CDG 1263:1270 ALG3-CDG 1263:1270 Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. 35211808 4 37 theme defects 578:584 arg1 unknown 634:640 unknown 634:640 unknown 634:640 The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. 35211808 4 37 theme defects 578:584 arg1 impact 552:557 The impact 548:557 The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components 548:621 The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. 35211808 7 38 dep in 1187:1188 arg1 vitro 1190:1194 vitro 1190:1194 vitro 1190:1194 Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. 35211808 3 39 theme diseases 487:494 arg1 group 468:472 a clinically heterogeneous group 441:472 a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG) 441:545 Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). 35211808 3 39 theme diseases 487:494 arg1 diseases 487:494 inherited diseases 477:494 inherited diseases called Congenital Disorders of Glycosylation (CDG) 477:545 Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). 35211808 0 40 theme prohormone 16:25 arg1 N-glycosylation 27:41 Defective IGF-1 prohormone N-glycosylation 0:41 Defective IGF-1 prohormone N-glycosylation 0:41 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 9 41 theme IGF-1-induced 1316:1328 arg1 activation 1337:1346 IGF-1-induced IGF-1R activation 1316:1346 IGF-1-induced IGF-1R activation 1316:1346 IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. 35211808 13 42 from consequences 1921:1932 arg1 patients 1995:2002 patients 1995:2002 patients with CDG 1995:2011 Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG. 35211808 4 43 theme IGF-1/IGF-1R 589:600 arg1 components 612:621 IGF-1/IGF-1R signaling components 589:621 IGF-1/IGF-1R signaling components 589:621 The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. 35211808 11 44 theme IGF-1 1696:1700 arg1 secretion 1702:1710 fibroblasts IGF-1 secretion 1684:1710 fibroblasts IGF-1 secretion 1684:1710 ER-stress-related gene expression negatively correlated with fibroblasts IGF-1 secretion. 35211808 3 45 theme N-linked 410:417 arg1 glycosylation 419:431 N-linked glycosylation 410:431 N-linked glycosylation 410:431 Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). 35211808 13 46 with patients 1995:2002 arg1 CDG 2009:2011 CDG 2009:2011 CDG 2009:2011 Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG. 35211808 0 47 theme IGF-1 55:59 arg1 activation 80:89 reduced IGF-1 receptor signaling activation 47:89 reduced IGF-1 receptor signaling activation 47:89 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 0 48 gly N-glycosylation 27:41 arg1 disorders 105:113 congenital disorders 94:113 congenital disorders of glycosylation 94:130 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 6 49 gly hypoglycosylation 973:989 arg1 proIGF-1Ea 998:1007 the proIGF-1Ea 994:1007 the proIGF-1Ea 994:1007 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). 35211808 3 50 theme Congenital 503:512 arg1 Disorders 514:522 Congenital Disorders 503:522 Congenital Disorders of Glycosylation (CDG) 503:545 Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). 35211808 9 51 theme most 1361:1364 arg1 fibroblasts 1375:1385 most PMM2-CDG fibroblasts 1361:1385 most PMM2-CDG fibroblasts 1361:1385 IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. 35211808 12 52 theme signaling 1843:1851 arg1 components 1853:1862 IGF-1/IGF-1R signaling components 1830:1862 IGF-1/IGF-1R signaling components 1830:1862 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 2 53 theme proper 370:375 arg1 N-glycosylation 377:391 proper N-glycosylation 370:391 proper N-glycosylation 370:391 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. 35211808 0 54 theme receptor 61:68 arg1 activation 80:89 reduced IGF-1 receptor signaling activation 47:89 reduced IGF-1 receptor signaling activation 47:89 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 6 55 theme ALG3-CDG 906:913 arg1 fibroblasts 954:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts 906:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts 906:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). 35211808 10 56 theme Endoplasmic 1524:1534 arg1 Reticulum 1536:1544 Endoplasmic Reticulum 1524:1544 Endoplasmic Reticulum (ER) stress genes 1524:1562 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35211808 10 56 theme Endoplasmic 1524:1534 arg1 ER 1547:1548 ER 1547:1548 ER 1547:1548 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35211808 7 57 theme in 1187:1188 arg1 data 1196:1199 our in vitro data 1183:1199 our in vitro data 1183:1199 Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. 35211808 2 58 theme precursor 351:359 arg1 processing 261:270 The correct processing 249:270 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor 249:359 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. 35211808 12 59 theme direct 1751:1756 arg1 link 1758:1761 a direct link 1749:1761 a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components 1749:1862 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 5 60 with patients 688:695 arg1 n = 7 727:731 n = 7 727:731 n = 7 727:731 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 60 with patients 688:695 arg1 [PMM2-CDG 716:724 different CDG [PMM2-CDG 702:724 different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1) 702:787 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 10 61 theme genes 1558:1562 arg1 upregulation 1508:1519 a slight upregulation 1499:1519 a slight upregulation of Endoplasmic Reticulum (ER) stress genes 1499:1562 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35211808 13 62 theme activity 1983:1990 arg1 consequences 1921:1932 the clinical consequences 1908:1932 the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG 1908:2011 Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG. 35211808 7 63 theme IGF-1 1075:1079 arg1 concentration 1087:1099 Lower IGF-1 serum concentration 1069:1099 Lower IGF-1 serum concentration 1069:1099 Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. 35211808 2 64 theme prohormone 287:296 arg1 processing 261:270 The correct processing 249:270 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor 249:359 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. 35211808 9 65 theme ERK1/2 1421:1426 arg1 phosphorylation 1428:1442 decreased ERK1/2 phosphorylation 1411:1442 decreased ERK1/2 phosphorylation 1411:1442 IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. 35211808 10 66 from stress 1602:1607 arg1 cells 1616:1620 CDG cells 1612:1620 CDG cells 1612:1620 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35211808 12 67 theme new 1733:1735 arg1 evidence 1737:1744 new evidence 1733:1744 new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components 1733:1862 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 12 68 located found 1795:1799 arg1 CDG 1804:1806 CDG 1804:1806 CDG 1804:1806 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 12 68 located found 1795:1799 arg2 defects 1787:1793 N-glycosylation defects 1771:1793 N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components 1771:1862 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 12 68 located found 1795:1799 arg1 impairment 1816:1825 the impairment 1812:1825 the impairment of IGF-1/IGF-1R signaling components 1812:1862 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 11 69 theme gene 1641:1644 arg1 expression 1646:1655 ER-stress-related gene expression 1623:1655 ER-stress-related gene expression 1623:1655 ER-stress-related gene expression negatively correlated with fibroblasts IGF-1 secretion. 35211808 5 70 theme dermal 664:669 arg1 fibroblasts 671:681 dermal fibroblasts 664:681 dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1) 664:787 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 13 71 theme IGF-1 1954:1958 arg1 availability 1960:1971 reduced systemic IGF-1 availability 1937:1971 reduced systemic IGF-1 availability 1937:1971 Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG. 35211808 2 72 theme IGF-1 319:323 arg1 IGF-1R 335:340 IGF-1R 335:340 IGF-1R 335:340 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. 35211808 2 72 theme IGF-1 319:323 arg1 receptor 325:332 IGF-1 receptor 319:332 the IGF-1 receptor (IGF-1R) peptide precursor 315:359 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. 35211808 8 73 theme reduced 1215:1221 arg1 level 1241:1245 reduced IGF-1R expression level 1215:1245 reduced IGF-1R expression level 1215:1245 Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. 35211808 5 74 theme IGF-1R 879:884 arg1 activity 896:903 IGF-1R signaling activity 879:903 IGF-1R signaling activity 879:903 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 8 75 theme expression 1230:1239 arg1 level 1241:1245 reduced IGF-1R expression level 1215:1245 reduced IGF-1R expression level 1215:1245 Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. 35211808 3 76 link N-linked 410:417 arg1 glycosylation 419:431 N-linked glycosylation 410:431 N-linked glycosylation 410:431 Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). 35211808 6 77 theme GMPPB-CDG 926:934 arg1 fibroblasts 954:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts 906:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts 906:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). 35211808 0 78 from activation 80:89 arg1 disorders 105:113 congenital disorders 94:113 congenital disorders of glycosylation 94:130 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 10 79 theme mild 1594:1597 arg1 stress 1602:1607 mild ER stress 1594:1607 mild ER stress in CDG cells 1594:1620 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35211808 5 80 theme CDG 712:714 arg1 n = 7 727:731 n = 7 727:731 n = 7 727:731 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 80 theme CDG 712:714 arg1 [PMM2-CDG 716:724 different CDG [PMM2-CDG 702:724 different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1) 702:787 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 81 theme signaling 886:894 arg1 activity 896:903 IGF-1R signaling activity 879:903 IGF-1R signaling activity 879:903 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 6 82 theme ALG8-CDG 916:923 arg1 fibroblasts 954:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts 906:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts 906:964 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). 35211808 13 83 theme clinical 1912:1919 arg1 consequences 1921:1932 the clinical consequences 1908:1932 the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG 1908:2011 Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG. 35211808 1 84 theme growth 150:155 arg1 IGF-1 167:171 IGF-1 167:171 IGF-1 167:171 The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. 35211808 1 84 theme growth 150:155 arg1 factor-1 157:164 insulin-like growth factor-1 137:164 The insulin-like growth factor-1 (IGF-1) signaling pathway 133:190 The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. 35211808 6 85 theme IGF-1 1019:1023 arg1 secretion 1025:1033 lower IGF-1 secretion 1013:1033 lower IGF-1 secretion 1013:1033 ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). 35211808 5 86 theme secretion 854:862 arg1 efficiency 864:873 IGF-1 secretion efficiency 848:873 IGF-1 secretion efficiency 848:873 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 0 87 from N-glycosylation 27:41 arg1 disorders 105:113 congenital disorders 94:113 congenital disorders of glycosylation 94:130 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 0 88 theme congenital 94:103 arg1 disorders 105:113 congenital disorders 94:113 congenital disorders of glycosylation 94:130 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 5 89 dep [PMM2-CDG 716:724 arg1 n = 1 782:786 n = 1 782:786 n = 1 782:786 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 89 dep [PMM2-CDG 716:724 arg1 ALG3-CDG 735:742 ALG3-CDG 735:742 different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1) 702:787 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 89 dep [PMM2-CDG 716:724 arg1 n = 1 763:767 n = 1 763:767 n = 1 763:767 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 89 dep [PMM2-CDG 716:724 arg1 n = 2 745:749 n = 2 745:749 n = 2 745:749 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 89 dep [PMM2-CDG 716:724 arg1 GMPPB-CDG 771:779 GMPPB-CDG 771:779 different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1) 702:787 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 5 89 dep [PMM2-CDG 716:724 arg1 ALG8-CDG 753:760 ALG8-CDG 753:760 different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1) 702:787 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 1 90 theme development 236:246 arg1 regulation 211:220 the regulation 207:220 the regulation of growth and development 207:246 The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. 35211808 0 91 theme IGF-1 10:14 arg1 N-glycosylation 27:41 Defective IGF-1 prohormone N-glycosylation 0:41 Defective IGF-1 prohormone N-glycosylation 0:41 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 4 92 theme signaling 602:610 arg1 components 612:621 IGF-1/IGF-1R signaling components 589:621 IGF-1/IGF-1R signaling components 589:621 The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. 35211808 10 93 theme CDG 1476:1478 arg1 fibroblasts 1480:1490 CDG fibroblasts 1476:1490 CDG fibroblasts 1476:1490 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35211808 11 94 theme fibroblasts 1684:1694 arg1 secretion 1702:1710 fibroblasts IGF-1 secretion 1684:1710 fibroblasts IGF-1 secretion 1684:1710 ER-stress-related gene expression negatively correlated with fibroblasts IGF-1 secretion. 35211808 0 95 theme reduced 47:53 arg1 activation 80:89 reduced IGF-1 receptor signaling activation 47:89 reduced IGF-1 receptor signaling activation 47:89 Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. 35211808 9 96 theme IGF-1R 1330:1335 arg1 activation 1337:1346 IGF-1-induced IGF-1R activation 1316:1346 IGF-1-induced IGF-1R activation 1316:1346 IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. 35211808 3 97 theme inherited 477:485 arg1 diseases 487:494 inherited diseases 477:494 inherited diseases called Congenital Disorders of Glycosylation (CDG) 477:545 Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). 35211808 4 98 from impact 552:557 arg1 components 612:621 IGF-1/IGF-1R signaling components 589:621 IGF-1/IGF-1R signaling components 589:621 The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. 35211808 12 99 theme IGF-1/IGF-1R 1830:1841 arg1 components 1853:1862 IGF-1/IGF-1R signaling components 1830:1862 IGF-1/IGF-1R signaling components 1830:1862 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 3 100 theme glycosylation 419:431 arg1 Deficiencies 394:405 Deficiencies 394:405 Deficiencies of N-linked glycosylation 394:431 Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). 35211808 4 101 theme N-glycosylation 562:576 arg1 defects 578:584 N-glycosylation defects 562:584 N-glycosylation defects 562:584 The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. 35211808 10 102 theme slight 1501:1506 arg1 upregulation 1508:1519 a slight upregulation 1499:1519 a slight upregulation of Endoplasmic Reticulum (ER) stress genes 1499:1562 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35211808 3 103 theme Glycosylation 527:539 arg1 Disorders 514:522 Congenital Disorders 503:522 Congenital Disorders of Glycosylation (CDG) 503:545 Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). 35211808 5 104 from patients 688:695 arg1 fibroblasts 671:681 dermal fibroblasts 664:681 dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1) 664:787 In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. 35211808 12 105 theme components 1853:1862 arg1 CDG 1804:1806 CDG 1804:1806 CDG 1804:1806 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 12 105 theme components 1853:1862 arg1 impairment 1816:1825 the impairment 1812:1825 the impairment of IGF-1/IGF-1R signaling components 1812:1862 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 2 106 theme receptor 325:332 arg1 precursor 351:359 the IGF-1 receptor (IGF-1R) peptide precursor 315:359 the IGF-1 receptor (IGF-1R) peptide precursor 315:359 The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. 35211808 9 107 theme PMM2-CDG 1366:1373 arg1 fibroblasts 1375:1385 most PMM2-CDG fibroblasts 1361:1385 most PMM2-CDG fibroblasts 1361:1385 IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. 35211808 12 108 theme N-glycosylation 1771:1785 arg1 defects 1787:1793 N-glycosylation defects 1771:1793 N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components 1771:1862 This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. 35211808 10 109 theme Reticulum 1536:1544 arg1 genes 1558:1562 Endoplasmic Reticulum (ER) stress genes 1524:1562 Endoplasmic Reticulum (ER) stress genes 1524:1562 In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. 35186771 4 0 from mutations 605:613 arg1 gliomas 618:624 gliomas 618:624 gliomas 618:624 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 11 1 theme tumor-associated 1432:1447 arg1 macrophages 1449:1459 tumor-associated macrophages 1432:1459 tumor-associated macrophages 1432:1459 Further analysis confirmed that MAN2B1 was closely associated with the markers of M2 macrophages and tumor-associated macrophages. 35186771 8 2 theme cell 1058:1061 arg1 lines 1063:1067 cell lines 1058:1067 cell lines 1058:1067 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 8 3 theme western 978:984 arg1 blot 986:989 western blot 978:989 western blot 978:989 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 10 4 theme M1 1315:1316 arg1 macrophages 1318:1328 M1 macrophages 1315:1328 M1 macrophages 1315:1328 Moreover, MAN2B1 expression was strongly correlated with M2 macrophages and weakly correlated with M1 macrophages. 35186771 11 5 theme macrophages 1449:1459 arg1 markers 1402:1408 the markers 1398:1408 the markers of M2 macrophages and tumor-associated macrophages 1398:1459 Further analysis confirmed that MAN2B1 was closely associated with the markers of M2 macrophages and tumor-associated macrophages. 35186771 1 6 link N-linked 209:216 arg1 glycoproteins 218:230 N-linked glycoproteins 209:230 N-linked glycoproteins 209:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 1 7 theme lysosomal 140:148 arg1 gene 127:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 1 7 theme lysosomal 140:148 arg1 alpha-d-mannosidase 150:168 lysosomal alpha-d-mannosidase 140:168 lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins 140:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 5 8 theme molecular 718:726 arg1 features 728:735 malignant clinical and molecular features 695:735 malignant clinical and molecular features 695:735 We found that MAN2B1 was elevated in glioma and was correlated with malignant clinical and molecular features. 35186771 1 9 gly glycoproteins 218:230 arg1 glycoproteins 218:230 N-linked glycoproteins 209:230 N-linked glycoproteins 209:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 1 10 theme 2B 106:107 arg1 gene 127:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 1 10 theme 2B 106:107 arg1 alpha-d-mannosidase 150:168 lysosomal alpha-d-mannosidase 140:168 lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins 140:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 4 11 theme Glioma 463:468 arg1 datasets 483:490 the Chinese Glioma Genome Atlas datasets 451:490 the Chinese Glioma Genome Atlas datasets 451:490 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 4 12 from datasets 483:490 arg1 data 413:416 RNA-seq data 405:416 RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets 405:490 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 4 13 theme RNA-seq 405:411 arg1 data 413:416 RNA-seq data 405:416 RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets 405:490 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 7 14 theme Different 823:831 arg1 frequencies 833:843 Different frequencies 823:843 Different frequencies of somatic mutations 823:864 Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. 35186771 9 15 theme enrichment 1126:1135 arg1 analysis 1137:1144 Functional enrichment analysis 1115:1144 Functional enrichment analysis 1115:1144 Functional enrichment analysis showed that MAN2B1 was involved in immune and inflammation processes. 35186771 4 16 from prognosis 582:590 arg1 gliomas 618:624 gliomas 618:624 gliomas 618:624 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 4 17 theme Chinese 455:461 arg1 datasets 483:490 the Chinese Glioma Genome Atlas datasets 451:490 the Chinese Glioma Genome Atlas datasets 451:490 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 8 18 theme immunohistochemistry 996:1015 arg1 staining 1017:1024 immunohistochemistry staining 996:1024 immunohistochemistry staining 996:1024 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 11 19 theme M2 1413:1414 arg1 macrophages 1416:1426 M2 macrophages 1413:1426 M2 macrophages 1413:1426 Further analysis confirmed that MAN2B1 was closely associated with the markers of M2 macrophages and tumor-associated macrophages. 35186771 4 20 theme Atlas 477:481 arg1 datasets 483:490 the Chinese Glioma Genome Atlas datasets 451:490 the Chinese Glioma Genome Atlas datasets 451:490 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 11 21 theme Further 1331:1337 arg1 analysis 1339:1346 Further analysis 1331:1346 Further analysis 1331:1346 Further analysis confirmed that MAN2B1 was closely associated with the markers of M2 macrophages and tumor-associated macrophages. 35186771 8 22 theme glioma 1031:1036 arg1 samples 1046:1052 glioma patient samples 1031:1052 glioma patient samples 1031:1052 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 10 23 theme MAN2B1 1226:1231 arg1 expression 1233:1242 MAN2B1 expression 1226:1242 MAN2B1 expression 1226:1242 Moreover, MAN2B1 expression was strongly correlated with M2 macrophages and weakly correlated with M1 macrophages. 35186771 7 24 theme mutations 856:864 arg1 frequencies 833:843 Different frequencies 823:843 Different frequencies of somatic mutations 823:864 Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. 35186771 8 25 used used 1074:1077 arg2 blot 986:989 western blot 978:989 western blot 978:989 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 8 25 used used 1074:1077 arg2 staining 1017:1024 immunohistochemistry staining 996:1024 immunohistochemistry staining 996:1024 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 8 25 used used 1074:1077 arg2 reaction 968:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 8 25 used used 1074:1077 arg2 lines 1063:1067 cell lines 1058:1067 cell lines 1058:1067 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 0 26 theme Infiltration 7:18 arg1 Biomarker 60:68 a Novel Prognostic Biomarker 41:68 a Novel Prognostic Biomarker for Glioma 41:79 Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. 35186771 0 26 theme Infiltration 7:18 arg1 MAN2B1 31:36 Immune Infiltration Associated MAN2B1 0:36 Immune Infiltration Associated MAN2B1 0:36 Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. 35186771 4 27 theme Genome 470:475 arg1 datasets 483:490 the Chinese Glioma Genome Atlas datasets 451:490 the Chinese Glioma Genome Atlas datasets 451:490 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 8 28 theme bioinformatic 1091:1103 arg1 findings 1105:1112 bioinformatic findings 1091:1112 bioinformatic findings 1091:1112 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 6 29 theme poor 789:792 arg1 outcomes 794:801 poor outcomes 789:801 poor outcomes in glioma patients 789:820 Upregulated expression of MAN2B1 is prognostic for poor outcomes in glioma patients. 35186771 1 30 theme Mannosidase 82:92 arg1 gene 127:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 1 30 theme Mannosidase 82:92 arg1 alpha-d-mannosidase 150:168 lysosomal alpha-d-mannosidase 140:168 lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins 140:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 2 31 from Alteration 233:242 arg1 MAN2B1 247:252 MAN2B1 247:252 MAN2B1 247:252 Alteration in MAN2B1 has been proved to be accountable for several diseases. 35186771 5 32 theme clinical 705:712 arg1 features 728:735 malignant clinical and molecular features 695:735 malignant clinical and molecular features 695:735 We found that MAN2B1 was elevated in glioma and was correlated with malignant clinical and molecular features. 35186771 0 33 theme Immune 0:5 arg1 Biomarker 60:68 a Novel Prognostic Biomarker 41:68 a Novel Prognostic Biomarker for Glioma 41:79 Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. 35186771 0 33 theme Immune 0:5 arg1 MAN2B1 31:36 Immune Infiltration Associated MAN2B1 0:36 Immune Infiltration Associated MAN2B1 0:36 Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. 35186771 9 34 theme Functional 1115:1124 arg1 analysis 1137:1144 Functional enrichment analysis 1115:1144 Functional enrichment analysis 1115:1144 Functional enrichment analysis showed that MAN2B1 was involved in immune and inflammation processes. 35186771 1 35 theme Alpha 94:98 arg1 gene 127:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 1 35 theme Alpha 94:98 arg1 alpha-d-mannosidase 150:168 lysosomal alpha-d-mannosidase 140:168 lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins 140:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 8 36 theme patient 1038:1044 arg1 samples 1046:1052 glioma patient samples 1031:1052 glioma patient samples 1031:1052 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 1 37 theme Class 100:104 arg1 gene 127:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 1 37 theme Class 100:104 arg1 alpha-d-mannosidase 150:168 lysosomal alpha-d-mannosidase 140:168 lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins 140:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 7 38 theme somatic 848:854 arg1 mutations 856:864 somatic mutations 848:864 somatic mutations 848:864 Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. 35186771 1 39 theme ordered 186:192 arg1 degradation 194:204 the ordered degradation 182:204 the ordered degradation of N-linked glycoproteins 182:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 0 40 theme Associated 20:29 arg1 Biomarker 60:68 a Novel Prognostic Biomarker 41:68 a Novel Prognostic Biomarker for Glioma 41:79 Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. 35186771 0 40 theme Associated 20:29 arg1 MAN2B1 31:36 Immune Infiltration Associated MAN2B1 0:36 Immune Infiltration Associated MAN2B1 0:36 Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. 35186771 5 41 theme malignant 695:703 arg1 features 728:735 malignant clinical and molecular features 695:735 malignant clinical and molecular features 695:735 We found that MAN2B1 was elevated in glioma and was correlated with malignant clinical and molecular features. 35186771 2 42 theme several 292:298 arg1 diseases 300:307 several diseases 292:307 several diseases 292:307 Alteration in MAN2B1 has been proved to be accountable for several diseases. 35186771 6 43 theme glioma 806:811 arg1 patients 813:820 glioma patients 806:820 glioma patients 806:820 Upregulated expression of MAN2B1 is prognostic for poor outcomes in glioma patients. 35186771 11 44 theme macrophages 1416:1426 arg1 markers 1402:1408 the markers 1398:1408 the markers of M2 macrophages and tumor-associated macrophages 1398:1459 Further analysis confirmed that MAN2B1 was closely associated with the markers of M2 macrophages and tumor-associated macrophages. 35186771 4 45 theme clinicopathological 552:570 arg1 features 572:579 clinicopathological features 552:579 clinicopathological features 552:579 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 4 46 from Atlas 441:445 arg1 data 413:416 RNA-seq data 405:416 RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets 405:490 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 4 47 theme Genome 434:439 arg1 Atlas 441:445 The Cancer Genome Atlas 423:445 The Cancer Genome Atlas 423:445 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 10 48 theme M2 1273:1274 arg1 macrophages 1276:1286 M2 macrophages 1273:1286 M2 macrophages 1273:1286 Moreover, MAN2B1 expression was strongly correlated with M2 macrophages and weakly correlated with M1 macrophages. 35186771 6 49 from outcomes 794:801 arg1 patients 813:820 glioma patients 806:820 glioma patients 806:820 Upregulated expression of MAN2B1 is prognostic for poor outcomes in glioma patients. 35186771 12 50 theme prognostic 1500:1509 arg1 biomarker 1511:1519 a potential prognostic biomarker 1488:1519 a potential prognostic biomarker in glioma 1488:1529 Taken together, MAN2B1 is a potential prognostic biomarker in glioma and associates with immune infiltration. 35186771 12 50 theme prognostic 1500:1509 arg1 MAN2B1 1478:1483 MAN2B1 1478:1483 MAN2B1 1478:1483 Taken together, MAN2B1 is a potential prognostic biomarker in glioma and associates with immune infiltration. 35186771 8 51 theme quantitative 938:949 arg1 reaction 968:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 1 52 theme N-linked 209:216 arg1 glycoproteins 218:230 N-linked glycoproteins 209:230 N-linked glycoproteins 209:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 0 53 theme Prognostic 49:58 arg1 Biomarker 60:68 a Novel Prognostic Biomarker 41:68 a Novel Prognostic Biomarker for Glioma 41:79 Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. 35186771 0 53 theme Prognostic 49:58 arg1 MAN2B1 31:36 Immune Infiltration Associated MAN2B1 0:36 Immune Infiltration Associated MAN2B1 0:36 Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. 35186771 12 54 from biomarker 1511:1519 arg1 glioma 1524:1529 glioma 1524:1529 glioma 1524:1529 Taken together, MAN2B1 is a potential prognostic biomarker in glioma and associates with immune infiltration. 35186771 3 55 dep MAN2B1 344:349 arg1 malignancy 362:371 malignancy 362:371 malignancy 362:371 However, the relationship between MAN2B1 and glioma malignancy remains unclear. 35186771 12 56 theme potential 1490:1498 arg1 biomarker 1511:1519 a potential prognostic biomarker 1488:1519 a potential prognostic biomarker in glioma 1488:1529 Taken together, MAN2B1 is a potential prognostic biomarker in glioma and associates with immune infiltration. 35186771 12 56 theme potential 1490:1498 arg1 MAN2B1 1478:1483 MAN2B1 1478:1483 MAN2B1 1478:1483 Taken together, MAN2B1 is a potential prognostic biomarker in glioma and associates with immune infiltration. 35186771 6 57 theme MAN2B1 764:769 arg1 expression 750:759 Upregulated expression 738:759 Upregulated expression of MAN2B1 738:769 Upregulated expression of MAN2B1 is prognostic for poor outcomes in glioma patients. 35186771 1 58 theme Member 109:114 arg1 gene 127:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 1 58 theme Member 109:114 arg1 alpha-d-mannosidase 150:168 lysosomal alpha-d-mannosidase 140:168 lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins 140:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 0 59 theme Novel 43:47 arg1 Biomarker 60:68 a Novel Prognostic Biomarker 41:68 a Novel Prognostic Biomarker for Glioma 41:79 Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. 35186771 0 59 theme Novel 43:47 arg1 MAN2B1 31:36 Immune Infiltration Associated MAN2B1 0:36 Immune Infiltration Associated MAN2B1 0:36 Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma. 35186771 7 60 located found 871:875 arg1 gliomas 880:886 gliomas 880:886 gliomas between high and low MAN2B1 expression 880:925 Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. 35186771 7 60 located found 871:875 arg2 frequencies 833:843 Different frequencies 823:843 Different frequencies of somatic mutations 823:864 Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. 35186771 12 61 theme immune 1551:1556 arg1 infiltration 1558:1569 immune infiltration 1551:1569 immune infiltration 1551:1569 Taken together, MAN2B1 is a potential prognostic biomarker in glioma and associates with immune infiltration. 35186771 8 62 theme chain 962:966 arg1 reaction 968:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 8 63 theme Real-time 928:936 arg1 reaction 968:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 8 64 theme polymerase 951:960 arg1 reaction 968:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 1 65 theme glycoproteins 218:230 arg1 degradation 194:204 the ordered degradation 182:204 the ordered degradation of N-linked glycoproteins 182:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 9 66 theme immune 1181:1186 arg1 processes 1205:1213 immune and inflammation processes 1181:1213 immune and inflammation processes 1181:1213 Functional enrichment analysis showed that MAN2B1 was involved in immune and inflammation processes. 35186771 4 67 theme Cancer 427:432 arg1 Atlas 441:445 The Cancer Genome Atlas 423:445 The Cancer Genome Atlas 423:445 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 6 68 theme Upregulated 738:748 arg1 expression 750:759 Upregulated expression 738:759 Upregulated expression of MAN2B1 738:769 Upregulated expression of MAN2B1 is prognostic for poor outcomes in glioma patients. 35186771 1 69 theme MAN2B1 119:124 arg1 gene 127:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene 82:130 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 1 69 theme MAN2B1 119:124 arg1 alpha-d-mannosidase 150:168 lysosomal alpha-d-mannosidase 140:168 lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins 140:230 Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. 35186771 7 70 theme low 905:907 arg1 expression 916:925 high and low MAN2B1 expression 896:925 high and low MAN2B1 expression 896:925 Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. 35186771 4 71 theme somatic 597:603 arg1 mutations 605:613 somatic mutations 597:613 somatic mutations in gliomas 597:624 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 9 72 theme inflammation 1192:1203 arg1 processes 1205:1213 immune and inflammation processes 1181:1213 immune and inflammation processes 1181:1213 Functional enrichment analysis showed that MAN2B1 was involved in immune and inflammation processes. 35186771 8 73 from samples 1046:1052 arg1 lines 1063:1067 cell lines 1058:1067 cell lines 1058:1067 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 8 73 from samples 1046:1052 arg1 staining 1017:1024 immunohistochemistry staining 996:1024 immunohistochemistry staining 996:1024 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 8 73 from samples 1046:1052 arg1 reaction 968:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction 928:975 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 8 73 from samples 1046:1052 arg1 blot 986:989 western blot 978:989 western blot 978:989 Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. 35186771 7 74 theme MAN2B1 909:914 arg1 expression 916:925 high and low MAN2B1 expression 896:925 high and low MAN2B1 expression 896:925 Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. 35186771 4 75 from MAN2B1 541:546 arg1 gliomas 618:624 gliomas 618:624 gliomas 618:624 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 4 76 from features 572:579 arg1 gliomas 618:624 gliomas 618:624 gliomas 618:624 In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. 35186771 7 77 theme high 896:899 arg1 expression 916:925 high and low MAN2B1 expression 896:925 high and low MAN2B1 expression 896:925 Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. 37253229 0 0 theme No 78:79 arg1 S-Glyco-Modification 81:100 No S-Glyco-Modification 78:100 No S-Glyco-Modification 78:100 Metabolic Glycan Labeling in Primary Neurons Enabled by Unnatural Sugars with No S-Glyco-Modification. 37253229 0 1 from Labeling 17:24 arg1 Neurons 37:43 Primary Neurons 29:43 Primary Neurons 29:43 Metabolic Glycan Labeling in Primary Neurons Enabled by Unnatural Sugars with No S-Glyco-Modification. 37253229 4 2 theme cytoskeleton 726:737 arg1 organization 739:750 microtubule cytoskeleton organization 714:750 microtubule cytoskeleton organization 714:750 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 2 3 theme cultured 348:355 arg1 neurons 365:371 cultured primary neurons 348:371 cultured primary neurons 348:371 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 5 4 gly sialylated 1063:1072 arg1 glycans 1074:1080 cell-surface sialylated glycans 1050:1080 cell-surface sialylated glycans 1050:1080 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 1 5 theme primary 153:159 arg1 cultures 168:175 primary neuron cultures 153:175 primary neuron cultures 153:175 It is of great interest to probe glycosylation in primary neuron cultures. 37253229 5 6 from visualization 1033:1045 arg1 neurons 1226:1232 primary neurons 1218:1232 primary neurons 1218:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 7 theme sialylated 1063:1072 arg1 glycans 1074:1080 cell-surface sialylated glycans 1050:1080 cell-surface sialylated glycans 1050:1080 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 3 8 with reactions 570:578 arg1 cysteines 593:601 protein cysteines 585:601 protein cysteines 585:601 Here, we uncovered that neuron cytotoxicity of per-O-acetylated unnatural sugars was related to their reactions with protein cysteines via non-enzymatic S-glyco-modification. 37253229 6 9 theme 345 1312:1314 arg1 glycoproteins 1316:1328 345 glycoproteins 1312:1328 345 glycoproteins 1312:1328 Particularly, a total of 505 sialylated N-glycosylation sites distributed on 345 glycoproteins were identified by 1,6-Pr2ManNAz. 37253229 3 10 theme unnatural 532:540 arg1 sugars 542:547 per-O-acetylated unnatural sugars 515:547 per-O-acetylated unnatural sugars 515:547 Here, we uncovered that neuron cytotoxicity of per-O-acetylated unnatural sugars was related to their reactions with protein cysteines via non-enzymatic S-glyco-modification. 37253229 4 11 theme extension 781:789 arg1 development 810:820 neuron projection development 792:820 neuron projection development 792:820 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 4 11 theme extension 781:789 arg1 axonogenesis 827:838 axonogenesis 827:838 axonogenesis 827:838 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 4 11 theme extension 781:789 arg1 organization 739:750 microtubule cytoskeleton organization 714:750 microtubule cytoskeleton organization 714:750 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 4 11 theme extension 781:789 arg1 regulation 762:771 positive regulation 753:771 positive regulation of axon extension 753:789 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 5 12 from MGL 861:863 arg1 neurons 885:891 cultured primary neurons 868:891 cultured primary neurons 868:891 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 4 13 theme neuron 792:797 arg1 development 810:820 neuron projection development 792:820 neuron projection development 792:820 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 0 14 with Sugars 66:71 arg1 S-Glyco-Modification 81:100 No S-Glyco-Modification 78:100 No S-Glyco-Modification 78:100 Metabolic Glycan Labeling in Primary Neurons Enabled by Unnatural Sugars with No S-Glyco-Modification. 37253229 3 15 theme sugars 542:547 arg1 cytotoxicity 499:510 neuron cytotoxicity 492:510 neuron cytotoxicity of per-O-acetylated unnatural sugars 492:547 Here, we uncovered that neuron cytotoxicity of per-O-acetylated unnatural sugars was related to their reactions with protein cysteines via non-enzymatic S-glyco-modification. 37253229 4 16 theme positive 753:760 arg1 regulation 762:771 positive regulation 753:771 positive regulation of axon extension 753:789 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 5 17 theme modification 1196:1207 arg1 sites 1209:1213 the modification sites 1192:1213 the modification sites in primary neurons 1192:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 2 18 theme glycan 280:285 arg1 labeling 287:294 metabolic glycan labeling 270:294 metabolic glycan labeling (MGL) 270:300 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 2 18 theme glycan 280:285 arg1 MGL 297:299 MGL 297:299 MGL 297:299 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 1 19 theme neuron 161:166 arg1 cultures 168:175 primary neuron cultures 153:175 primary neuron cultures 153:175 It is of great interest to probe glycosylation in primary neuron cultures. 37253229 5 20 from neurons 1226:1232 arg1 identification 1136:1149 large-scale identification 1124:1149 large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons 1124:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 20 from neurons 1226:1232 arg1 visualization 1033:1045 visualization 1033:1045 visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, 1033:1118 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 21 theme sites 1209:1213 arg1 identification 1136:1149 large-scale identification 1124:1149 large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons 1124:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 21 theme sites 1209:1213 arg1 visualization 1033:1045 visualization 1033:1045 visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, 1033:1118 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 2 22 theme metabolic 270:278 arg1 labeling 287:294 metabolic glycan labeling 270:294 metabolic glycan labeling (MGL) 270:300 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 2 22 theme metabolic 270:278 arg1 MGL 297:299 MGL 297:299 MGL 297:299 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 2 23 used utilized 258:265 arg2 sugars 224:229 per-O-acetylated clickable unnatural sugars 187:229 per-O-acetylated clickable unnatural sugars 187:229 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 0 24 theme Glycan 10:15 arg1 Labeling 17:24 Metabolic Glycan Labeling 0:24 Metabolic Glycan Labeling in Primary Neurons 0:43 Metabolic Glycan Labeling in Primary Neurons Enabled by Unnatural Sugars with No S-Glyco-Modification. 37253229 4 25 theme axon 776:779 arg1 extension 781:789 axon extension 776:789 axon extension 776:789 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 5 26 theme S-glyco-modification-free 920:944 arg1 ManNAz 973:978 ManNAz 973:978 ManNAz 973:978 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 26 theme S-glyco-modification-free 920:944 arg1 sugars 956:961 S-glyco-modification-free unnatural sugars 920:961 S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons 920:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 26 theme S-glyco-modification-free 920:944 arg1 1,3-Pr2ManNAz 981:993 1,3-Pr2ManNAz 981:993 1,3-Pr2ManNAz 981:993 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 26 theme S-glyco-modification-free 920:944 arg1 1,6-Pr2ManNAz 1000:1012 1,6-Pr2ManNAz 1000:1012 1,6-Pr2ManNAz 1000:1012 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 0 27 theme Metabolic 0:8 arg1 Labeling 17:24 Metabolic Glycan Labeling 0:24 Metabolic Glycan Labeling in Primary Neurons 0:43 Metabolic Glycan Labeling in Primary Neurons Enabled by Unnatural Sugars with No S-Glyco-Modification. 37253229 6 28 gly sialylated 1264:1273 arg1 sites 1291:1295 505 sialylated N-glycosylation sites 1260:1295 505 sialylated N-glycosylation sites distributed on 345 glycoproteins 1260:1328 Particularly, a total of 505 sialylated N-glycosylation sites distributed on 345 glycoproteins were identified by 1,6-Pr2ManNAz. 37253229 4 29 theme biological 682:691 arg1 functions 693:701 biological functions 682:701 biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis 682:838 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 4 30 theme modified 647:654 arg1 proteins 656:663 The modified proteins 643:663 The modified proteins 643:663 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 5 31 from sites 1209:1213 arg1 neurons 1226:1232 primary neurons 1218:1232 primary neurons 1218:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 6 32 theme sites 1291:1295 arg1 total 1251:1255 a total 1249:1255 a total of 505 sialylated N-glycosylation sites distributed on 345 glycoproteins 1249:1328 Particularly, a total of 505 sialylated N-glycosylation sites distributed on 345 glycoproteins were identified by 1,6-Pr2ManNAz. 37253229 5 33 theme cell-surface 1050:1061 arg1 glycans 1074:1080 cell-surface sialylated glycans 1050:1080 cell-surface sialylated glycans 1050:1080 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 34 theme sialylated 1154:1163 arg1 glycoproteins 1174:1186 sialylated N-linked glycoproteins 1154:1186 sialylated N-linked glycoproteins 1154:1186 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 4 35 theme microtubule 714:724 arg1 organization 739:750 microtubule cytoskeleton organization 714:750 microtubule cytoskeleton organization 714:750 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 5 36 theme primary 877:883 arg1 neurons 885:891 cultured primary neurons 868:891 cultured primary neurons 868:891 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 6 37 gly N-glycosylation 1275:1289 arg2 sites 1291:1295 505 sialylated N-glycosylation sites 1260:1295 505 sialylated N-glycosylation sites distributed on 345 glycoproteins 1260:1328 Particularly, a total of 505 sialylated N-glycosylation sites distributed on 345 glycoproteins were identified by 1,6-Pr2ManNAz. 37253229 6 37 gly N-glycosylation 1275:1289 arg2 505 1260:1262 505 1260:1262 505 1260:1262 Particularly, a total of 505 sialylated N-glycosylation sites distributed on 345 glycoproteins were identified by 1,6-Pr2ManNAz. 37253229 5 38 theme N-linked 1165:1172 arg1 glycoproteins 1174:1186 sialylated N-linked glycoproteins 1154:1186 sialylated N-linked glycoproteins 1154:1186 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 3 39 theme protein 585:591 arg1 cysteines 593:601 protein cysteines 585:601 protein cysteines 585:601 Here, we uncovered that neuron cytotoxicity of per-O-acetylated unnatural sugars was related to their reactions with protein cysteines via non-enzymatic S-glyco-modification. 37253229 5 40 theme unnatural 946:954 arg1 ManNAz 973:978 ManNAz 973:978 ManNAz 973:978 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 40 theme unnatural 946:954 arg1 sugars 956:961 S-glyco-modification-free unnatural sugars 920:961 S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons 920:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 40 theme unnatural 946:954 arg1 1,3-Pr2ManNAz 981:993 1,3-Pr2ManNAz 981:993 1,3-Pr2ManNAz 981:993 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 40 theme unnatural 946:954 arg1 1,6-Pr2ManNAz 1000:1012 1,6-Pr2ManNAz 1000:1012 1,6-Pr2ManNAz 1000:1012 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 0 41 theme Primary 29:35 arg1 Neurons 37:43 Primary Neurons 29:43 Primary Neurons 29:43 Metabolic Glycan Labeling in Primary Neurons Enabled by Unnatural Sugars with No S-Glyco-Modification. 37253229 2 42 theme cell 453:456 arg1 cultures 458:465 primary neuron cell cultures 438:465 primary neuron cell cultures 438:465 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 5 43 theme glycoproteins 1174:1186 arg1 identification 1136:1149 large-scale identification 1124:1149 large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons 1124:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 43 theme glycoproteins 1174:1186 arg1 visualization 1033:1045 visualization 1033:1045 visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, 1033:1118 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 2 44 theme neuron 446:451 arg1 cultures 458:465 primary neuron cell cultures 438:465 primary neuron cell cultures 438:465 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 5 45 from glycoproteins 1174:1186 arg1 neurons 1226:1232 primary neurons 1218:1232 primary neurons 1218:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 1 46 gly glycosylation 136:148 arg1 cultures 168:175 primary neuron cultures 153:175 primary neuron cultures 153:175 It is of great interest to probe glycosylation in primary neuron cultures. 37253229 6 47 gly glycoproteins 1316:1328 arg1 glycoproteins 1316:1328 345 glycoproteins 1312:1328 345 glycoproteins 1312:1328 Particularly, a total of 505 sialylated N-glycosylation sites distributed on 345 glycoproteins were identified by 1,6-Pr2ManNAz. 37253229 5 48 theme sialylation 1107:1117 arg1 dynamics 1095:1102 the dynamics 1091:1102 the dynamics of sialylation 1091:1117 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 2 49 theme primary 438:444 arg1 cultures 458:465 primary neuron cell cultures 438:465 primary neuron cell cultures 438:465 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 6 50 theme N-glycosylation 1275:1289 arg1 sites 1291:1295 505 sialylated N-glycosylation sites 1260:1295 505 sialylated N-glycosylation sites distributed on 345 glycoproteins 1260:1328 Particularly, a total of 505 sialylated N-glycosylation sites distributed on 345 glycoproteins were identified by 1,6-Pr2ManNAz. 37253229 2 51 theme unnatural 214:222 arg1 sugars 224:229 per-O-acetylated clickable unnatural sugars 187:229 per-O-acetylated clickable unnatural sugars 187:229 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 5 52 theme large-scale 1124:1134 arg1 identification 1136:1149 large-scale identification 1124:1149 large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons 1124:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 1 53 theme great 112:116 arg1 interest 118:125 great interest 112:125 great interest 112:125 It is of great interest to probe glycosylation in primary neuron cultures. 37253229 2 54 theme clickable 204:212 arg1 sugars 224:229 per-O-acetylated clickable unnatural sugars 187:229 per-O-acetylated clickable unnatural sugars 187:229 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 5 55 theme glycans 1074:1080 arg1 identification 1136:1149 large-scale identification 1124:1149 large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons 1124:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 55 theme glycans 1074:1080 arg1 visualization 1033:1045 visualization 1033:1045 visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, 1033:1118 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 2 56 with compatible 422:431 arg1 cultures 458:465 primary neuron cell cultures 438:465 primary neuron cell cultures 438:465 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 5 57 gly sialylated 1154:1163 arg1 glycoproteins 1174:1186 sialylated N-linked glycoproteins 1154:1186 sialylated N-linked glycoproteins 1154:1186 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 3 58 theme per-O-acetylated 515:530 arg1 sugars 542:547 per-O-acetylated unnatural sugars 515:547 per-O-acetylated unnatural sugars 515:547 Here, we uncovered that neuron cytotoxicity of per-O-acetylated unnatural sugars was related to their reactions with protein cysteines via non-enzymatic S-glyco-modification. 37253229 2 59 theme per-O-acetylated 187:202 arg1 sugars 224:229 per-O-acetylated clickable unnatural sugars 187:229 per-O-acetylated clickable unnatural sugars 187:229 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 37253229 4 60 theme projection 799:808 arg1 development 810:820 neuron projection development 792:820 neuron projection development 792:820 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 6 61 theme sialylated 1264:1273 arg1 sites 1291:1295 505 sialylated N-glycosylation sites 1260:1295 505 sialylated N-glycosylation sites distributed on 345 glycoproteins 1260:1328 Particularly, a total of 505 sialylated N-glycosylation sites distributed on 345 glycoproteins were identified by 1,6-Pr2ManNAz. 37253229 4 62 theme related 703:709 arg1 functions 693:701 biological functions 682:701 biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis 682:838 The modified proteins were enriched in biological functions related to microtubule cytoskeleton organization, positive regulation of axon extension, neuron projection development, and axonogenesis. 37253229 5 63 from identification 1136:1149 arg1 neurons 1226:1232 primary neurons 1218:1232 primary neurons 1218:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 64 link N-linked 1165:1172 arg1 glycoproteins 1174:1186 sialylated N-linked glycoproteins 1154:1186 sialylated N-linked glycoproteins 1154:1186 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 5 65 theme cultured 868:875 arg1 neurons 885:891 cultured primary neurons 868:891 cultured primary neurons 868:891 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 3 66 theme neuron 492:497 arg1 cytotoxicity 499:510 neuron cytotoxicity 492:510 neuron cytotoxicity of per-O-acetylated unnatural sugars 492:547 Here, we uncovered that neuron cytotoxicity of per-O-acetylated unnatural sugars was related to their reactions with protein cysteines via non-enzymatic S-glyco-modification. 37253229 5 67 gly glycoproteins 1174:1186 arg1 glycoproteins 1174:1186 sialylated N-linked glycoproteins 1154:1186 sialylated N-linked glycoproteins 1154:1186 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 0 68 theme Unnatural 56:64 arg1 Sugars 66:71 Unnatural Sugars 56:71 Unnatural Sugars with No S-Glyco-Modification 56:100 Metabolic Glycan Labeling in Primary Neurons Enabled by Unnatural Sugars with No S-Glyco-Modification. 37253229 5 69 theme primary 1218:1224 arg1 neurons 1226:1232 primary neurons 1218:1232 primary neurons 1218:1232 We thus established MGL in cultured primary neurons without cytotoxicity using S-glyco-modification-free unnatural sugars including ManNAz, 1,3-Pr2ManNAz, and 1,6-Pr2ManNAz, which allowed for visualization of cell-surface sialylated glycans, probing the dynamics of sialylation, and large-scale identification of sialylated N-linked glycoproteins and the modification sites in primary neurons. 37253229 3 70 theme non-enzymatic 607:619 arg1 S-glyco-modification 621:640 non-enzymatic S-glyco-modification 607:640 non-enzymatic S-glyco-modification 607:640 Here, we uncovered that neuron cytotoxicity of per-O-acetylated unnatural sugars was related to their reactions with protein cysteines via non-enzymatic S-glyco-modification. 37253229 2 71 theme primary 357:363 arg1 neurons 365:371 cultured primary neurons 348:371 cultured primary neurons 348:371 However, per-O-acetylated clickable unnatural sugars, which have been routinely utilized in metabolic glycan labeling (MGL) for analyzing glycans, showed cytotoxicity to cultured primary neurons and thus led to the speculation that MGL was not compatible with primary neuron cell cultures. 35937530 4 0 theme inducer 900:906 arg1 Tm 908:909 the ER stress inducer Tm 886:909 the ER stress inducer Tm 886:909 In this study, we assessed the involvement of THE1 in ectopic lignin deposition caused by the ER stress inducer Tm. 35937530 3 1 theme wall 656:659 arg1 CWD 669:671 CWD 669:671 CWD 669:671 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 3 1 theme wall 656:659 arg1 damage 661:666 sense cell wall damage 645:666 sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) 645:751 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 8 2 theme CWD-induced 1574:1584 arg1 UPR 1586:1588 CWD-induced UPR 1574:1588 not only root growth inhibition and ectopic lignin deposition caused by ER stress but also CWD-induced UPR 1483:1588 These results showed that THE1 is involved in not only root growth inhibition and ectopic lignin deposition caused by ER stress but also CWD-induced UPR. 35937530 5 3 theme root 1070:1073 arg1 defects 1082:1088 root growth defects 1070:1088 root growth defects 1070:1088 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 1 4 theme reticulum 163:171 arg1 stress 178:183 Endoplasmic reticulum (ER) stress 151:183 Endoplasmic reticulum (ER) stress 151:183 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 35937530 7 5 theme the1-3 1329:1334 arg1 mutant 1336:1341 the the1-3 mutant 1325:1341 the the1-3 mutant 1325:1341 Conversely, in the the1-3 mutant, ISO-induced ectopic lignin deposition and the expression of BiP3 and ERdj3b were suppressed. 35937530 8 6 theme root 1492:1495 arg1 inhibition 1504:1513 root growth inhibition 1492:1513 root growth inhibition 1492:1513 These results showed that THE1 is involved in not only root growth inhibition and ectopic lignin deposition caused by ER stress but also CWD-induced UPR. 35937530 0 7 theme lignin 76:81 arg1 deposition 83:92 ectopic lignin deposition 68:92 ectopic lignin deposition 68:92 THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response. 35937530 6 8 theme binding 1250:1256 arg1 protein 1258:1264 binding protein 3 1250:1266 binding protein 3 (BiP3) 1250:1273 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 8 theme binding 1250:1256 arg1 BiP3 1269:1272 BiP3 1269:1272 BiP3 1269:1272 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 8 theme binding 1250:1256 arg1 genes 1244:1248 the UPR marker genes 1229:1248 the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b) 1229:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 9 theme lignin 1182:1187 arg1 deposition 1189:1198 ectopic lignin deposition 1174:1198 ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b) 1174:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 2 10 theme Arabidopsis 487:497 arg1 roots 499:503 Arabidopsis roots 487:503 Arabidopsis roots 487:503 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 3 11 theme sense 645:649 arg1 CWD 669:671 CWD 669:671 CWD 669:671 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 3 11 theme sense 645:649 arg1 damage 661:666 sense cell wall damage 645:666 sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) 645:751 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 2 12 theme lignin 551:556 arg1 deposition 558:567 ectopic lignin deposition 543:567 ectopic lignin deposition 543:567 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 8 13 theme ER 1555:1556 arg1 stress 1558:1563 ER stress 1555:1563 ER stress 1555:1563 These results showed that THE1 is involved in not only root growth inhibition and ectopic lignin deposition caused by ER stress but also CWD-induced UPR. 35937530 1 14 theme protein 248:254 arg1 folding 256:262 protein folding 248:262 protein folding 248:262 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 35937530 4 15 theme lignin 858:863 arg1 deposition 865:874 ectopic lignin deposition 850:874 ectopic lignin deposition caused by the ER stress inducer Tm 850:909 In this study, we assessed the involvement of THE1 in ectopic lignin deposition caused by the ER stress inducer Tm. 35937530 5 16 theme ectopic 1008:1014 arg1 deposition 1023:1032 ectopic lignin deposition 1008:1032 ectopic lignin deposition 1008:1032 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 2 17 theme ectopic 543:549 arg1 deposition 558:567 ectopic lignin deposition 543:567 ectopic lignin deposition 543:567 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 8 18 theme growth 1497:1502 arg1 inhibition 1504:1513 root growth inhibition 1492:1513 root growth inhibition 1492:1513 These results showed that THE1 is involved in not only root growth inhibition and ectopic lignin deposition caused by ER stress but also CWD-induced UPR. 35937530 2 19 theme ER 342:343 arg1 stress 345:350 ER stress 342:350 ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, 342:449 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 5 20 theme ER 1130:1131 arg1 stress 1133:1138 ER stress 1130:1138 ER stress 1130:1138 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 0 21 theme wall 104:107 arg1 response 141:148 cell wall damage-induced unfolded protein response 99:148 cell wall damage-induced unfolded protein response 99:148 THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response. 35937530 5 22 theme lignin 1016:1021 arg1 deposition 1023:1032 ectopic lignin deposition 1008:1032 ectopic lignin deposition 1008:1032 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 6 23 theme ectopic 1174:1180 arg1 deposition 1189:1198 ectopic lignin deposition 1174:1198 ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b) 1174:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 8 24 theme lignin 1527:1532 arg1 deposition 1534:1543 ectopic lignin deposition 1519:1543 ectopic lignin deposition 1519:1543 These results showed that THE1 is involved in not only root growth inhibition and ectopic lignin deposition caused by ER stress but also CWD-induced UPR. 35937530 0 25 theme cell 99:102 arg1 response 141:148 cell wall damage-induced unfolded protein response 99:148 cell wall damage-induced unfolded protein response 99:148 THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response. 35937530 2 26 theme glycan 433:438 arg1 synthesis 440:448 N-linked glycan synthesis 424:448 N-linked glycan synthesis 424:448 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 2 27 theme stress 366:371 arg1 inducers 373:380 ER stress inducers 363:380 ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, 363:449 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 2 27 theme stress 366:371 arg1 tunicamycin 390:400 tunicamycin 390:400 tunicamycin (Tm) 390:405 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 2 28 theme N-linked 424:431 arg1 synthesis 440:448 N-linked glycan synthesis 424:448 N-linked glycan synthesis 424:448 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 2 29 theme synthesis 440:448 arg1 tunicamycin 390:400 tunicamycin 390:400 tunicamycin (Tm) 390:405 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 2 29 theme synthesis 440:448 arg1 inhibitor 411:419 an inhibitor 408:419 an inhibitor of N-linked glycan synthesis 408:448 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 7 30 theme ectopic 1356:1362 arg1 deposition 1371:1380 ISO-induced ectopic lignin deposition 1344:1380 ISO-induced ectopic lignin deposition 1344:1380 Conversely, in the the1-3 mutant, ISO-induced ectopic lignin deposition and the expression of BiP3 and ERdj3b were suppressed. 35937530 2 31 theme ectopic 458:464 arg1 deposition 473:482 ectopic lignin deposition 458:482 ectopic lignin deposition in Arabidopsis roots 458:503 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 5 32 theme growth 1075:1080 arg1 defects 1082:1088 root growth defects 1070:1088 root growth defects 1070:1088 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 2 33 theme ER 363:364 arg1 inducers 373:380 ER stress inducers 363:380 ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, 363:449 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 2 33 theme ER 363:364 arg1 tunicamycin 390:400 tunicamycin 390:400 tunicamycin (Tm) 390:405 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 6 34 theme UPR 1233:1235 arg1 3b 1297:1298 ER-localized DnaJ 3b 1279:1298 ER-localized DnaJ 3b (ERdj3b) 1279:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 34 theme UPR 1233:1235 arg1 protein 1258:1264 binding protein 3 1250:1266 binding protein 3 (BiP3) 1250:1273 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 34 theme UPR 1233:1235 arg1 genes 1244:1248 the UPR marker genes 1229:1248 the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b) 1229:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 35 theme genes 1244:1248 arg1 expression 1215:1224 the expression 1211:1224 ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b) 1174:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 35 theme genes 1244:1248 arg1 deposition 1189:1198 ectopic lignin deposition 1174:1198 ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b) 1174:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 36 theme ISO 1152:1154 arg1 treatment 1156:1164 ISO treatment 1152:1164 ISO treatment 1152:1164 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 7 37 theme lignin 1364:1369 arg1 deposition 1371:1380 ISO-induced ectopic lignin deposition 1344:1380 ISO-induced ectopic lignin deposition 1344:1380 Conversely, in the the1-3 mutant, ISO-induced ectopic lignin deposition and the expression of BiP3 and ERdj3b were suppressed. 35937530 4 38 from involvement 827:837 arg1 deposition 865:874 ectopic lignin deposition 850:874 ectopic lignin deposition caused by the ER stress inducer Tm 850:909 In this study, we assessed the involvement of THE1 in ectopic lignin deposition caused by the ER stress inducer Tm. 35937530 6 39 theme marker 1237:1242 arg1 3b 1297:1298 ER-localized DnaJ 3b 1279:1298 ER-localized DnaJ 3b (ERdj3b) 1279:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 39 theme marker 1237:1242 arg1 protein 1258:1264 binding protein 3 1250:1266 binding protein 3 (BiP3) 1250:1273 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 39 theme marker 1237:1242 arg1 genes 1244:1248 the UPR marker genes 1229:1248 the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b) 1229:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 7 40 theme ERdj3b 1413:1418 arg1 deposition 1371:1380 ISO-induced ectopic lignin deposition 1344:1380 ISO-induced ectopic lignin deposition 1344:1380 Conversely, in the the1-3 mutant, ISO-induced ectopic lignin deposition and the expression of BiP3 and ERdj3b were suppressed. 35937530 7 40 theme ERdj3b 1413:1418 arg1 expression 1390:1399 the expression 1386:1399 the expression of BiP3 and ERdj3b 1386:1418 Conversely, in the the1-3 mutant, ISO-induced ectopic lignin deposition and the expression of BiP3 and ERdj3b were suppressed. 35937530 0 41 theme unfolded 124:131 arg1 response 141:148 cell wall damage-induced unfolded protein response 99:148 cell wall damage-induced unfolded protein response 99:148 THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response. 35937530 2 42 link N-linked 424:431 arg1 synthesis 440:448 N-linked glycan synthesis 424:448 N-linked glycan synthesis 424:448 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 8 43 theme ectopic 1519:1525 arg1 deposition 1534:1543 ectopic lignin deposition 1519:1543 ectopic lignin deposition 1519:1543 These results showed that THE1 is involved in not only root growth inhibition and ectopic lignin deposition caused by ER stress but also CWD-induced UPR. 35937530 1 44 theme unfolded 195:202 arg1 UPRs 223:226 UPRs 223:226 UPRs 223:226 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 35937530 1 44 theme unfolded 195:202 arg1 responses 212:220 unfolded protein responses 195:220 unfolded protein responses (UPRs) 195:227 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 35937530 5 45 theme ectopic 1094:1100 arg1 deposition 1109:1118 ectopic lignin deposition 1094:1118 ectopic lignin deposition 1094:1118 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 0 46 theme damage-induced 109:122 arg1 response 141:148 cell wall damage-induced unfolded protein response 99:148 cell wall damage-induced unfolded protein response 99:148 THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response. 35937530 5 47 theme root 981:984 arg1 inhibition 993:1002 Tm-induced root growth inhibition 970:1002 Tm-induced root growth inhibition 970:1002 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 1 48 theme protein 204:210 arg1 UPRs 223:226 UPRs 223:226 UPRs 223:226 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 35937530 1 48 theme protein 204:210 arg1 responses 212:220 unfolded protein responses 195:220 unfolded protein responses (UPRs) 195:227 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 35937530 0 49 theme root 44:47 arg1 inhibition 56:65 tunicamycin-induced root growth inhibition 24:65 tunicamycin-induced root growth inhibition 24:65 THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response. 35937530 5 50 theme lignin 1102:1107 arg1 deposition 1109:1118 ectopic lignin deposition 1094:1118 ectopic lignin deposition 1094:1118 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 4 51 theme ectopic 850:856 arg1 deposition 865:874 ectopic lignin deposition 850:874 ectopic lignin deposition caused by the ER stress inducer Tm 850:909 In this study, we assessed the involvement of THE1 in ectopic lignin deposition caused by the ER stress inducer Tm. 35937530 5 52 theme growth 986:991 arg1 inhibition 993:1002 Tm-induced root growth inhibition 970:1002 Tm-induced root growth inhibition 970:1002 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 4 53 theme ER 890:891 arg1 Tm 908:909 the ER stress inducer Tm 886:909 the ER stress inducer Tm 886:909 In this study, we assessed the involvement of THE1 in ectopic lignin deposition caused by the ER stress inducer Tm. 35937530 6 54 theme ER-localized 1279:1290 arg1 ERdj3b 1301:1306 ERdj3b 1301:1306 ERdj3b 1301:1306 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 54 theme ER-localized 1279:1290 arg1 3b 1297:1298 ER-localized DnaJ 3b 1279:1298 ER-localized DnaJ 3b (ERdj3b) 1279:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 54 theme ER-localized 1279:1290 arg1 genes 1244:1248 the UPR marker genes 1229:1248 the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b) 1229:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 0 55 theme tunicamycin-induced 24:42 arg1 inhibition 56:65 tunicamycin-induced root growth inhibition 24:65 tunicamycin-induced root growth inhibition 24:65 THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response. 35937530 1 56 theme specific 285:292 arg1 expression 299:308 specific gene expression 285:308 specific gene expression 285:308 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 35937530 0 57 theme protein 133:139 arg1 response 141:148 cell wall damage-induced unfolded protein response 99:148 cell wall damage-induced unfolded protein response 99:148 THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response. 35937530 3 58 theme cellulose 700:708 arg1 inhibitors 719:728 cellulose synthase inhibitors 700:728 cellulose synthase inhibitors such as isoxaben (ISO) 700:751 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 3 58 theme cellulose 700:708 arg1 isoxaben 738:745 isoxaben 738:745 isoxaben (ISO) 738:751 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 2 59 theme lignin 466:471 arg1 deposition 473:482 ectopic lignin deposition 458:482 ectopic lignin deposition in Arabidopsis roots 458:503 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 6 60 dep genes 1244:1248 arg1 genes 1244:1248 the UPR marker genes 1229:1248 the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b) 1229:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 60 dep genes 1244:1248 arg1 ERdj3b 1301:1306 ERdj3b 1301:1306 ERdj3b 1301:1306 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 60 dep genes 1244:1248 arg1 protein 1258:1264 binding protein 3 1250:1266 binding protein 3 (BiP3) 1250:1273 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 60 dep genes 1244:1248 arg1 BiP3 1269:1272 BiP3 1269:1272 BiP3 1269:1272 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 60 dep genes 1244:1248 arg1 3b 1297:1298 ER-localized DnaJ 3b 1279:1298 ER-localized DnaJ 3b (ERdj3b) 1279:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 1 61 theme gene 294:297 arg1 expression 299:308 specific gene expression 285:308 specific gene expression 285:308 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 35937530 7 62 theme BiP3 1404:1407 arg1 deposition 1371:1380 ISO-induced ectopic lignin deposition 1344:1380 ISO-induced ectopic lignin deposition 1344:1380 Conversely, in the the1-3 mutant, ISO-induced ectopic lignin deposition and the expression of BiP3 and ERdj3b were suppressed. 35937530 7 62 theme BiP3 1404:1407 arg1 expression 1390:1399 the expression 1386:1399 the expression of BiP3 and ERdj3b 1386:1418 Conversely, in the the1-3 mutant, ISO-induced ectopic lignin deposition and the expression of BiP3 and ERdj3b were suppressed. 35937530 5 63 theme THE1 945:948 arg1 mutation 933:940 The loss-of-function mutation 912:940 The loss-of-function mutation of THE1, the1-3, 912:957 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 0 64 theme growth 49:54 arg1 inhibition 56:65 tunicamycin-induced root growth inhibition 24:65 tunicamycin-induced root growth inhibition 24:65 THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response. 35937530 1 65 theme expression 299:308 arg1 control 274:280 the control 270:280 the control of specific gene expression 270:308 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 35937530 4 66 theme THE1 842:845 arg1 involvement 827:837 the involvement 823:837 the involvement of THE1 in ectopic lignin deposition caused by the ER stress inducer Tm 823:909 In this study, we assessed the involvement of THE1 in ectopic lignin deposition caused by the ER stress inducer Tm. 35937530 2 67 from deposition 473:482 arg1 roots 499:503 Arabidopsis roots 487:503 Arabidopsis roots 487:503 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 3 68 theme kinase 604:609 arg1 THE1 621:624 THE1 621:624 THE1 621:624 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 3 68 theme kinase 604:609 arg1 THESEUS1 611:618 The receptor-like kinase THESEUS1 586:618 The receptor-like kinase THESEUS1 (THE1) 586:625 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 7 69 theme ISO-induced 1344:1354 arg1 deposition 1371:1380 ISO-induced ectopic lignin deposition 1344:1380 ISO-induced ectopic lignin deposition 1344:1380 Conversely, in the the1-3 mutant, ISO-induced ectopic lignin deposition and the expression of BiP3 and ERdj3b were suppressed. 35937530 3 70 theme synthase 710:717 arg1 inhibitors 719:728 cellulose synthase inhibitors 700:728 cellulose synthase inhibitors such as isoxaben (ISO) 700:751 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 3 70 theme synthase 710:717 arg1 isoxaben 738:745 isoxaben 738:745 isoxaben (ISO) 738:751 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 2 71 theme previous 315:322 arg1 study 324:328 Our previous study 311:328 Our previous study 311:328 Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. 35937530 4 72 theme stress 893:898 arg1 Tm 908:909 the ER stress inducer Tm 886:909 the ER stress inducer Tm 886:909 In this study, we assessed the involvement of THE1 in ectopic lignin deposition caused by the ER stress inducer Tm. 35937530 3 73 theme receptor-like 590:602 arg1 THE1 621:624 THE1 621:624 THE1 621:624 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 3 73 theme receptor-like 590:602 arg1 THESEUS1 611:618 The receptor-like kinase THESEUS1 586:618 The receptor-like kinase THESEUS1 (THE1) 586:625 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 3 74 theme ectopic 769:775 arg1 deposition 784:793 ectopic lignin deposition 769:793 ectopic lignin deposition 769:793 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 0 75 theme ectopic 68:74 arg1 deposition 83:92 ectopic lignin deposition 68:92 ectopic lignin deposition 68:92 THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response. 35937530 5 76 theme Tm-induced 970:979 arg1 inhibition 993:1002 Tm-induced root growth inhibition 970:1002 Tm-induced root growth inhibition 970:1002 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 6 77 theme DnaJ 1292:1295 arg1 ERdj3b 1301:1306 ERdj3b 1301:1306 ERdj3b 1301:1306 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 77 theme DnaJ 1292:1295 arg1 3b 1297:1298 ER-localized DnaJ 3b 1279:1298 ER-localized DnaJ 3b (ERdj3b) 1279:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 6 77 theme DnaJ 1292:1295 arg1 genes 1244:1248 the UPR marker genes 1229:1248 the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b) 1229:1307 Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). 35937530 3 78 theme lignin 777:782 arg1 deposition 784:793 ectopic lignin deposition 769:793 ectopic lignin deposition 769:793 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 3 79 theme cell 651:654 arg1 CWD 669:671 CWD 669:671 CWD 669:671 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 3 79 theme cell 651:654 arg1 damage 661:666 sense cell wall damage 645:666 sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) 645:751 The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. 35937530 5 80 theme loss-of-function 916:931 arg1 mutation 933:940 The loss-of-function mutation 912:940 The loss-of-function mutation of THE1, the1-3, 912:957 The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. 35937530 1 81 theme Endoplasmic 151:161 arg1 ER 174:175 ER 174:175 ER 174:175 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 35937530 1 81 theme Endoplasmic 151:161 arg1 reticulum 163:171 Endoplasmic reticulum 151:171 Endoplasmic reticulum (ER) stress 151:183 Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. 37277060 7 0 theme in 1160:1161 arg1 condition 1169:1177 in vitro condition 1160:1177 in vitro condition with high glucose and lipid 1160:1205 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 3 1 theme liver 579:583 arg1 samples 585:591 Human liver samples 573:591 Human liver samples 573:591 MATERIALS AND METHODS Human liver samples obtained from subjects with/without NASH were analyzed. 37277060 9 2 theme mice 1589:1592 arg1 model 1594:1598 the AMLN diet-induced NASH mice model 1562:1598 the AMLN diet-induced NASH mice model 1562:1598 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 10 3 from expression 1836:1845 arg1 NASH 1850:1853 NASH 1850:1853 NASH 1850:1853 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 7 4 theme intracellular 1209:1221 arg1 O-GlcNAcylation 1223:1237 intracellular O-GlcNAcylation 1209:1237 intracellular O-GlcNAcylation 1209:1237 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 1 5 theme inhibitors 202:211 arg1 effects 152:158 Steatosis reducing effects 133:158 Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) 133:251 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 2 6 from expression 365:374 arg1 livers 394:399 human livers 388:399 human livers 388:399 In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. 37277060 7 7 dep in 1160:1161 arg1 vitro 1163:1167 vitro 1163:1167 vitro 1163:1167 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 1 8 theme non-alcoholic 216:228 arg1 NASH 247:250 NASH 247:250 NASH 247:250 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 1 8 theme non-alcoholic 216:228 arg1 steatohepatitis 230:244 non-alcoholic steatohepatitis 216:244 non-alcoholic steatohepatitis (NASH) 216:251 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 5 9 theme SGLT2 954:958 arg1 inhibitor 960:968 an additional 10 weeks with/without SGLT2 inhibitor 918:968 an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 918:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 5 9 theme SGLT2 954:958 arg1 10 mg/kg/day 985:996 empagliflozin 10 mg/kg/day 971:996 empagliflozin 10 mg/kg/day 971:996 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 7 10 with condition 1169:1177 arg1 glucose 1189:1195 high glucose 1184:1195 high glucose 1184:1195 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 7 10 with condition 1169:1177 arg1 lipid 1201:1205 lipid 1201:1205 lipid 1201:1205 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 5 11 theme liver 870:874 arg1 NASH 876:879 Amylin liver NASH 863:879 a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 823:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 5 11 theme liver 870:874 arg1 AMLN 882:885 AMLN 882:885 AMLN 882:885 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 8 12 theme AMPK-TFEB 1537:1545 arg1 activation 1547:1556 AMPK-TFEB activation 1537:1556 AMPK-TFEB activation 1537:1556 In addition, decreased intracellular O-GlcNAcylation by SGLT2 inhibitor promoted autophagic flux through AMPK-TFEB activation. 37277060 4 13 theme normal 677:682 arg1 hepatocytes 684:694 human normal hepatocytes 671:694 human normal hepatocytes 671:694 For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. 37277060 9 14 theme NASH 1584:1587 arg1 model 1594:1598 the AMLN diet-induced NASH mice model 1562:1598 the AMLN diet-induced NASH mice model 1562:1598 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 7 15 dep condition 1149:1157 arg1 condition 1169:1177 in vitro condition 1160:1177 in vitro condition with high glucose and lipid 1160:1205 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 5 16 theme 10 weeks 932:939 arg1 inhibitor 960:968 an additional 10 weeks with/without SGLT2 inhibitor 918:968 an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 918:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 5 16 theme 10 weeks 932:939 arg1 10 mg/kg/day 985:996 empagliflozin 10 mg/kg/day 971:996 empagliflozin 10 mg/kg/day 971:996 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 9 17 theme autophagy 1683:1691 arg1 activation 1693:1702 autophagy activation 1683:1702 autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver 1683:1773 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 9 18 theme SGLT2 1601:1605 arg1 inhibitor 1607:1615 SGLT2 inhibitor 1601:1615 SGLT2 inhibitor 1601:1615 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 6 19 dep RESULTS 1000:1006 arg1 associated 1051:1060 associated 1051:1060 were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls 1046:1135 RESULTS Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. 37277060 7 20 theme glucose 1416:1422 arg1 uptake 1424:1429 hepatocellular glucose uptake 1401:1429 hepatocellular glucose uptake 1401:1429 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 1 21 dep AIMS 128:131 arg1 remains 315:321 remains 315:321 remains uncertain 315:331 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 1 21 dep AIMS 128:131 arg1 reported 275:282 reported 275:282 has been consistently reported in humans 253:292 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 4 22 theme SGLT2 733:737 arg1 inhibitor 739:747 SGLT2 inhibitor 733:747 SGLT2 inhibitor 733:747 For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. 37277060 1 23 theme Steatosis 133:141 arg1 effects 152:158 Steatosis reducing effects 133:158 Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) 133:251 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 9 24 from O-GlcNAcylation 1746:1760 arg1 liver 1769:1773 the liver 1765:1773 the liver 1765:1773 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 1 25 theme sodium-glucose 163:176 arg1 cotransporter 178:190 sodium-glucose cotransporter 2 163:192 sodium-glucose cotransporter 2 (SGLT2) inhibitors 163:211 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 1 25 theme sodium-glucose 163:176 arg1 SGLT2 195:199 SGLT2 195:199 SGLT2 195:199 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 9 26 from expression 1731:1740 arg1 liver 1769:1773 the liver 1765:1773 the liver 1765:1773 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 7 27 theme hepatocellular 1401:1414 arg1 uptake 1424:1429 hepatocellular glucose uptake 1401:1429 hepatocellular glucose uptake 1401:1429 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 2 28 theme glucose 469:475 arg1 uptake 477:482 hepatic glucose uptake 461:482 hepatic glucose uptake 461:482 In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. 37277060 0 29 theme Increased 0:8 arg1 expression 10:19 Increased expression 0:19 Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes 0:88 Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis. 37277060 8 30 theme intracellular 1455:1467 arg1 O-GlcNAcylation 1469:1483 decreased intracellular O-GlcNAcylation 1445:1483 decreased intracellular O-GlcNAcylation by SGLT2 inhibitor 1445:1502 In addition, decreased intracellular O-GlcNAcylation by SGLT2 inhibitor promoted autophagic flux through AMPK-TFEB activation. 37277060 2 31 theme SGLT2 440:444 arg1 inhibition 446:455 SGLT2 inhibition 440:455 SGLT2 inhibition 440:455 In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. 37277060 5 32 theme -cholesterol 850:861 arg1 diet 888:891 a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet 823:891 a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 823:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 3 33 dep MATERIALS 551:559 arg1 samples 585:591 Human liver samples 573:591 Human liver samples 573:591 MATERIALS AND METHODS Human liver samples obtained from subjects with/without NASH were analyzed. 37277060 0 34 theme cotransporter 39:51 arg1 expression 10:19 Increased expression 0:19 Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes 0:88 Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis. 37277060 6 35 theme increased 1067:1075 arg1 expression 1103:1112 increased SGLT2 and O-GlcNAcylation expression 1067:1112 increased SGLT2 and O-GlcNAcylation expression compared with controls 1067:1135 RESULTS Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. 37277060 10 36 theme glucose 1986:1992 arg1 uptake 1994:1999 hepatocellular glucose uptake 1971:1999 hepatocellular glucose uptake 1971:1999 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 7 37 theme high 1184:1187 arg1 glucose 1189:1195 high glucose 1184:1195 high glucose 1184:1195 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 1 38 theme reducing 143:150 arg1 effects 152:158 Steatosis reducing effects 133:158 Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) 133:251 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 9 39 theme SGLT2 1725:1729 arg1 expression 1731:1740 decreased SGLT2 expression 1715:1740 decreased SGLT2 expression 1715:1740 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 7 40 theme inhibitor 1338:1346 arg1 treatment 1348:1356 SGLT2 inhibitor treatment 1332:1356 SGLT2 inhibitor treatment 1332:1356 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 8 41 theme autophagic 1513:1522 arg1 flux 1524:1527 autophagic flux 1513:1527 autophagic flux 1513:1527 In addition, decreased intracellular O-GlcNAcylation by SGLT2 inhibitor promoted autophagic flux through AMPK-TFEB activation. 37277060 10 42 theme SGLT2 1830:1834 arg1 expression 1836:1845 increased SGLT2 expression 1820:1845 increased SGLT2 expression in NASH 1820:1853 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 2 43 from crosstalk 422:430 arg1 NASH 545:548 NASH 545:548 NASH 545:548 In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. 37277060 10 44 dep CONCLUSIONS 1776:1786 arg1 reveals 1868:1874 reveals 1868:1874 secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation 1859:2057 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 10 44 dep CONCLUSIONS 1776:1786 arg1 demonstrates 1807:1818 demonstrates 1807:1818 demonstrates increased SGLT2 expression in NASH 1807:1853 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 0 45 theme O-GlcNAcylation 59:73 arg1 expression 10:19 Increased expression 0:19 Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes 0:88 Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis. 37277060 4 46 theme in 653:654 arg1 studies 662:668 in vitro studies 653:668 in vitro studies 653:668 For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. 37277060 7 47 theme SGLT2 1298:1302 arg1 expression 1304:1313 SGLT2 expression 1298:1313 SGLT2 expression 1298:1313 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 3 48 theme Human 573:577 arg1 samples 585:591 Human liver samples 573:591 Human liver samples 573:591 MATERIALS AND METHODS Human liver samples obtained from subjects with/without NASH were analyzed. 37277060 7 49 theme NASH 1144:1147 arg1 condition 1149:1157 NASH condition 1144:1157 NASH condition (in vitro condition with high glucose and lipid) 1144:1206 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 10 50 theme novel 1880:1884 arg1 effect 1886:1891 the novel effect 1876:1891 the novel effect of SGLT2 inhibition on NASH 1876:1919 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 6 51 theme Liver 1008:1012 arg1 samples 1014:1020 Liver samples 1008:1020 Liver samples from subjects with NASH 1008:1044 RESULTS Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. 37277060 4 52 theme hepatoma 700:707 arg1 cells 709:713 hepatoma cells 700:713 hepatoma cells 700:713 For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. 37277060 10 53 theme inhibition 1902:1911 arg1 effect 1886:1891 the novel effect 1876:1891 the novel effect of SGLT2 inhibition on NASH 1876:1919 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 5 54 theme Amylin 863:868 arg1 NASH 876:879 Amylin liver NASH 863:879 a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 823:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 5 54 theme Amylin 863:868 arg1 AMLN 882:885 AMLN 882:885 AMLN 882:885 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 9 55 theme diet-induced 1571:1582 arg1 model 1594:1598 the AMLN diet-induced NASH mice model 1562:1598 the AMLN diet-induced NASH mice model 1562:1598 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 4 56 theme human 671:675 arg1 hepatocytes 684:694 human normal hepatocytes 671:694 human normal hepatocytes 671:694 For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. 37277060 5 57 theme additional 921:930 arg1 inhibitor 960:968 an additional 10 weeks with/without SGLT2 inhibitor 918:968 an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 918:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 5 57 theme additional 921:930 arg1 10 mg/kg/day 985:996 empagliflozin 10 mg/kg/day 971:996 empagliflozin 10 mg/kg/day 971:996 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 4 58 dep in 653:654 arg1 vitro 656:660 vitro 656:660 vitro 656:660 For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. 37277060 10 59 theme hepatocellular 1971:1984 arg1 uptake 1994:1999 hepatocellular glucose uptake 1971:1999 hepatocellular glucose uptake 1971:1999 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 5 60 theme with/without 941:952 arg1 inhibitor 960:968 an additional 10 weeks with/without SGLT2 inhibitor 918:968 an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 918:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 5 60 theme with/without 941:952 arg1 10 mg/kg/day 985:996 empagliflozin 10 mg/kg/day 971:996 empagliflozin 10 mg/kg/day 971:996 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 4 61 theme high-glucose 755:766 arg1 conditions 783:792 high-glucose and high-lipid conditions 755:792 high-glucose and high-lipid conditions 755:792 For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. 37277060 1 62 theme cotransporter 178:190 arg1 inhibitors 202:211 sodium-glucose cotransporter 2 (SGLT2) inhibitors 163:211 sodium-glucose cotransporter 2 (SGLT2) inhibitors 163:211 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 10 63 from effect 1886:1891 arg1 NASH 1916:1919 NASH 1916:1919 NASH 1916:1919 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 2 64 theme autophagic 520:529 arg1 regulation 531:540 autophagic regulation 520:540 autophagic regulation 520:540 In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. 37277060 6 65 with subjects 1027:1034 arg1 NASH 1041:1044 NASH 1041:1044 NASH 1041:1044 RESULTS Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. 37277060 0 66 theme non-alcoholic 97:109 arg1 steatohepatitis 111:125 non-alcoholic steatohepatitis 97:125 non-alcoholic steatohepatitis 97:125 Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis. 37277060 9 67 theme lipid 1628:1632 arg1 accumulation 1634:1645 lipid accumulation 1628:1645 lipid accumulation 1628:1645 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 0 68 from expression 10:19 arg1 hepatocytes 78:88 hepatocytes 78:88 hepatocytes 78:88 Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis. 37277060 7 69 theme inflammatory 1243:1254 arg1 markers 1256:1262 inflammatory markers 1243:1262 inflammatory markers 1243:1262 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 10 70 theme SGLT2 1896:1900 arg1 inhibition 1902:1911 SGLT2 inhibition 1896:1911 SGLT2 inhibition 1896:1911 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 9 71 theme AMLN 1566:1569 arg1 model 1594:1598 the AMLN diet-induced NASH mice model 1562:1598 the AMLN diet-induced NASH mice model 1562:1598 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 7 72 gly O-GlcNAcylation 1223:1237 arg1 hepatocytes 1282:1292 hepatocytes 1282:1292 hepatocytes 1282:1292 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 5 73 theme -fructose 835:843 arg1 diet 888:891 a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet 823:891 a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 823:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 2 74 theme hepatic 461:467 arg1 uptake 477:482 hepatic glucose uptake 461:482 hepatic glucose uptake 461:482 In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. 37277060 6 75 from subjects 1027:1034 arg1 samples 1014:1020 Liver samples 1008:1020 Liver samples from subjects with NASH 1008:1044 RESULTS Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. 37277060 4 76 theme high-lipid 772:781 arg1 conditions 783:792 high-glucose and high-lipid conditions 755:792 high-glucose and high-lipid conditions 755:792 For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. 37277060 2 77 theme human 388:392 arg1 livers 394:399 human livers 388:399 human livers 388:399 In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. 37277060 0 78 theme sodium-glucose 24:37 arg1 cotransporter 39:51 sodium-glucose cotransporter 2 24:53 sodium-glucose cotransporter 2 24:53 Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis. 37277060 1 79 from effects 152:158 arg1 NASH 247:250 NASH 247:250 NASH 247:250 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 1 79 from effects 152:158 arg1 steatohepatitis 230:244 non-alcoholic steatohepatitis 216:244 non-alcoholic steatohepatitis (NASH) 216:251 AIMS Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. 37277060 5 80 theme empagliflozin 971:983 arg1 inhibitor 960:968 an additional 10 weeks with/without SGLT2 inhibitor 918:968 an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 918:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 5 80 theme empagliflozin 971:983 arg1 10 mg/kg/day 985:996 empagliflozin 10 mg/kg/day 971:996 empagliflozin 10 mg/kg/day 971:996 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 6 81 theme O-GlcNAcylation 1087:1101 arg1 expression 1103:1112 increased SGLT2 and O-GlcNAcylation expression 1067:1112 increased SGLT2 and O-GlcNAcylation expression compared with controls 1067:1135 RESULTS Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. 37277060 8 82 theme decreased 1445:1453 arg1 O-GlcNAcylation 1469:1483 decreased intracellular O-GlcNAcylation 1445:1483 decreased intracellular O-GlcNAcylation by SGLT2 inhibitor 1445:1502 In addition, decreased intracellular O-GlcNAcylation by SGLT2 inhibitor promoted autophagic flux through AMPK-TFEB activation. 37277060 5 83 theme NASH 876:879 arg1 diet 888:891 a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet 823:891 a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 823:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 9 84 theme related 1704:1710 arg1 activation 1693:1702 autophagy activation 1683:1702 autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver 1683:1773 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 6 85 theme SGLT2 1077:1081 arg1 expression 1103:1112 increased SGLT2 and O-GlcNAcylation expression 1067:1112 increased SGLT2 and O-GlcNAcylation expression compared with controls 1067:1135 RESULTS Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. 37277060 2 86 theme intracellular 485:497 arg1 O-GlcNAcylation 499:513 intracellular O-GlcNAcylation 485:513 intracellular O-GlcNAcylation 485:513 In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. 37277060 10 87 theme uptake 1994:1999 arg1 inhibition 1957:1966 inhibition 1957:1966 inhibition of hepatocellular glucose uptake 1957:1999 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 5 88 theme high-fat 825:832 arg1 diet 888:891 a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet 823:891 a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day) 823:997 NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). 37277060 9 89 theme decreased 1715:1723 arg1 expression 1731:1740 decreased SGLT2 expression 1715:1740 decreased SGLT2 expression 1715:1740 In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. 37277060 7 90 theme SGLT2 1332:1336 arg1 treatment 1348:1356 SGLT2 inhibitor treatment 1332:1356 SGLT2 inhibitor treatment 1332:1356 Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. 37277060 8 91 theme SGLT2 1488:1492 arg1 inhibitor 1494:1502 SGLT2 inhibitor 1488:1502 SGLT2 inhibitor 1488:1502 In addition, decreased intracellular O-GlcNAcylation by SGLT2 inhibitor promoted autophagic flux through AMPK-TFEB activation. 37277060 10 92 theme intracellular 2029:2041 arg1 O-GlcNAcylation 2043:2057 intracellular O-GlcNAcylation 2029:2057 intracellular O-GlcNAcylation 2029:2057 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 10 93 theme increased 1820:1828 arg1 expression 1836:1845 increased SGLT2 expression 1820:1845 increased SGLT2 expression in NASH 1820:1853 CONCLUSIONS This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH by activating autophagy mediated by inhibition of hepatocellular glucose uptake and consequently decreasing intracellular O-GlcNAcylation. 37277060 2 94 theme SGLT2 379:383 arg1 expression 365:374 the expression 361:374 the expression of SGLT2 in human livers 361:399 In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. 36124017 4 0 theme small 321:325 arg1 molecules 327:335 secondary metabolic small molecules 301:335 secondary metabolic small molecules in FRAAB 301:344 Some studies have revealed secondary metabolic small molecules in FRAAB, but there are few reports on the polysaccharides of FRAAB (PFRAAB). 36124017 6 1 theme underlying 509:518 arg1 mechanism 520:528 underlying mechanism 509:528 underlying mechanism 509:528 The present study aimed to investigate the preliminary characterization and underlying mechanism of immune stimulation of PFRAAB. 36124017 13 2 theme receptor 1814:1821 arg1 expression 1790:1799 the expression 1786:1799 the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α 1786:1906 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 10 3 theme treated 1210:1216 arg1 mice 1218:1221 cyclophosphamide- (CCP-) treated mice 1185:1221 cyclophosphamide- (CCP-) treated mice 1185:1221 The immune stimulation of PFRAAB was investigated by using cyclophosphamide- (CCP-) treated mice and RAW264.7 cells. 36124017 10 4 theme CCP- 1204:1207 arg1 mice 1218:1221 cyclophosphamide- (CCP-) treated mice 1185:1221 cyclophosphamide- (CCP-) treated mice 1185:1221 The immune stimulation of PFRAAB was investigated by using cyclophosphamide- (CCP-) treated mice and RAW264.7 cells. 36124017 9 5 theme molecular 946:954 arg1 weight 956:961 The molecular weight 942:961 The molecular weight 942:961 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 4 6 from reports 365:371 arg1 polysaccharides 380:394 the polysaccharides 376:394 the polysaccharides of FRAAB (PFRAAB) 376:412 Some studies have revealed secondary metabolic small molecules in FRAAB, but there are few reports on the polysaccharides of FRAAB (PFRAAB). 36124017 5 7 theme Study 426:430 arg1 Aim 415:417 Aim 415:417 Aim of the Study. 415:431 Aim of the Study. 36124017 12 8 theme spleen 1507:1512 arg1 index 1525:1529 the spleen and thymus index 1503:1529 the spleen and thymus index 1503:1529 Compared with CCP-induced mice, PFRAAB significantly (p < 0.05 or p < 0.01) increased the spleen and thymus index, ameliorated injury to the spleen and thymus, and evaluated immunoglobulin levels. 36124017 3 9 theme asphodeloides 259:271 arg1 rhizome 236:242 the rhizome 232:242 the rhizome of Anemarrhena asphodeloides 232:271 (FRAAB) are byproducts of the rhizome of Anemarrhena asphodeloides. 36124017 4 10 theme few 361:363 arg1 reports 365:371 few reports 361:371 few reports on the polysaccharides of FRAAB (PFRAAB) 361:412 Some studies have revealed secondary metabolic small molecules in FRAAB, but there are few reports on the polysaccharides of FRAAB (PFRAAB). 36124017 13 11 theme nitric 1666:1671 arg1 NO 1680:1681 NO 1680:1681 NO 1680:1681 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 13 11 theme nitric 1666:1671 arg1 oxide 1673:1677 nitric oxide 1666:1677 nitric oxide (NO) 1666:1682 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 12 12 theme thymus 1518:1523 arg1 index 1525:1529 the spleen and thymus index 1503:1529 the spleen and thymus index 1503:1529 Compared with CCP-induced mice, PFRAAB significantly (p < 0.05 or p < 0.01) increased the spleen and thymus index, ameliorated injury to the spleen and thymus, and evaluated immunoglobulin levels. 36124017 13 13 theme RAW264.7 1755:1762 arg1 cells 1764:1768 RAW264.7 cells 1755:1768 RAW264.7 cells 1755:1768 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 15 14 theme asphodeloides 2128:2140 arg1 resources 2158:2166 Anemarrhena asphodeloides medicinal plant resources 2116:2166 Anemarrhena asphodeloides medicinal plant resources 2116:2166 Our present study provides a scientific basis for the comprehensive development of Anemarrhena asphodeloides medicinal plant resources. 36124017 14 15 theme immune-enhancing 2009:2024 arg1 drugs 2026:2030 immune-enhancing drugs 2009:2030 immune-enhancing drugs 2009:2030 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 15 16 theme comprehensive 2087:2099 arg1 development 2101:2111 the comprehensive development 2083:2111 the comprehensive development of Anemarrhena asphodeloides medicinal plant resources 2083:2166 Our present study provides a scientific basis for the comprehensive development of Anemarrhena asphodeloides medicinal plant resources. 36124017 6 17 theme stimulation 540:550 arg1 characterization 488:503 preliminary characterization 476:503 preliminary characterization 476:503 The present study aimed to investigate the preliminary characterization and underlying mechanism of immune stimulation of PFRAAB. 36124017 6 17 theme stimulation 540:550 arg1 mechanism 520:528 underlying mechanism 509:528 underlying mechanism 509:528 The present study aimed to investigate the preliminary characterization and underlying mechanism of immune stimulation of PFRAAB. 36124017 15 18 theme present 2037:2043 arg1 study 2045:2049 Our present study 2033:2049 Our present study 2033:2049 Our present study provides a scientific basis for the comprehensive development of Anemarrhena asphodeloides medicinal plant resources. 36124017 8 19 theme preliminary 812:822 arg1 characterization 824:839 The preliminary characterization 808:839 The preliminary characterization of PFRAAB 808:849 The preliminary characterization of PFRAAB was studied by ultraviolet (UV) scanning and Fourier Transform Infrared Reflection (FTIR). 36124017 4 20 theme FRAAB 399:403 arg1 polysaccharides 380:394 the polysaccharides 376:394 the polysaccharides of FRAAB (PFRAAB) 376:412 Some studies have revealed secondary metabolic small molecules in FRAAB, but there are few reports on the polysaccharides of FRAAB (PFRAAB). 36124017 4 21 from molecules 327:335 arg1 FRAAB 340:344 FRAAB 340:344 FRAAB 340:344 Some studies have revealed secondary metabolic small molecules in FRAAB, but there are few reports on the polysaccharides of FRAAB (PFRAAB). 36124017 9 22 theme gel 1023:1025 arg1 HPGPC 1054:1058 HPGPC 1054:1058 HPGPC 1054:1058 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 9 22 theme gel 1023:1025 arg1 chromatography 1038:1051 high-performance gel permeation chromatography 1006:1051 high-performance gel permeation chromatography (HPGPC) 1006:1059 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 13 23 theme p-IKB-α 1900:1906 arg1 expression 1790:1799 the expression 1786:1799 the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α 1786:1906 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 0 24 theme Anemarrhena 56:66 arg1 Root 48:51 the Fibrous Root 36:51 the Fibrous Root of Anemarrhena 36:66 A Water-Soluble Polysaccharide from the Fibrous Root of Anemarrhena asphodeloides Bge. 36124017 13 25 theme p-NF-κB 1876:1882 arg1 P65 1884:1886 p-NF-κB P65 1876:1886 p-NF-κB P65 1876:1886 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 12 26 theme p 1483:1483 arg1 < 1485:1485 p < 0.05 or p < 0.01 1471:1490 < 1485:1485 Compared with CCP-induced mice, PFRAAB significantly (p < 0.05 or p < 0.01) increased the spleen and thymus index, ameliorated injury to the spleen and thymus, and evaluated immunoglobulin levels. 36124017 14 27 theme immune 1937:1942 arg1 activity 1956:1963 immune stimulation activity 1937:1963 immune stimulation activity 1937:1963 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 7 28 theme water 639:643 arg1 extraction 645:654 hot water extraction 635:654 hot water extraction 635:654 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 12 29 theme immunoglobulin 1591:1604 arg1 levels 1606:1611 immunoglobulin levels 1591:1611 immunoglobulin levels 1591:1611 Compared with CCP-induced mice, PFRAAB significantly (p < 0.05 or p < 0.01) increased the spleen and thymus index, ameliorated injury to the spleen and thymus, and evaluated immunoglobulin levels. 36124017 11 30 dep Results 1243:1249 arg1 composed 1337:1344 composed 1337:1344 was mainly composed of arabinose (ara), galactose (gal), glucose (glc), and mannose (man) 1326:1414 Results A water-soluble PFRAAB was obtained with a molecular weight of 115 kDa and was mainly composed of arabinose (ara), galactose (gal), glucose (glc), and mannose (man). 36124017 11 30 dep Results 1243:1249 arg1 obtained 1278:1285 obtained 1278:1285 was obtained with a molecular weight of 115 kDa 1274:1320 Results A water-soluble PFRAAB was obtained with a molecular weight of 115 kDa and was mainly composed of arabinose (ara), galactose (gal), glucose (glc), and mannose (man). 36124017 13 31 theme NF-κB 1864:1868 arg1 P65 1871:1873 nuclear factor kappa-B (NF-κB) P65 1840:1873 nuclear factor kappa-B (NF-κB) P65 1840:1873 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 12 32 theme p 1471:1471 arg1 < 1473:1473 p < 0.05 or p < 0.01 1471:1490 < 1473:1473 Compared with CCP-induced mice, PFRAAB significantly (p < 0.05 or p < 0.01) increased the spleen and thymus index, ameliorated injury to the spleen and thymus, and evaluated immunoglobulin levels. 36124017 0 33 from Root 48:51 arg1 Polysaccharide 16:29 A Water-Soluble Polysaccharide 0:29 A Water-Soluble Polysaccharide from the Fibrous Root of Anemarrhena 0:66 A Water-Soluble Polysaccharide from the Fibrous Root of Anemarrhena asphodeloides Bge. 36124017 9 34 theme liquid 1082:1087 arg1 chromatography 1089:1102 high-performance liquid chromatography 1065:1102 high-performance liquid chromatography (HPLC) 1065:1109 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 9 34 theme liquid 1082:1087 arg1 HPLC 1105:1108 HPLC 1105:1108 HPLC 1105:1108 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 7 35 theme crude 589:593 arg1 polysaccharide 595:608 The crude polysaccharide 585:608 The crude polysaccharide of FRAAB 585:617 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 11 36 theme molecular 1294:1302 arg1 weight 1304:1309 a molecular weight 1292:1309 a molecular weight of 115 kDa 1292:1320 Results A water-soluble PFRAAB was obtained with a molecular weight of 115 kDa and was mainly composed of arabinose (ara), galactose (gal), glucose (glc), and mannose (man). 36124017 7 37 theme graphene 780:787 arg1 membrane 798:805 graphene dialysis membrane 780:805 graphene dialysis membrane 780:805 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 1 38 theme Enhancement 102:112 arg1 Effect 114:119 Its Immune Enhancement Effect 91:119 Its Immune Enhancement Effect in Vivo and in Vitro 91:140 and Its Immune Enhancement Effect in Vivo and in Vitro. 36124017 3 39 dep byproducts 218:227 arg1 FRAAB 207:211 FRAAB 207:211 FRAAB 207:211 (FRAAB) are byproducts of the rhizome of Anemarrhena asphodeloides. 36124017 13 40 theme necrosis 1716:1723 arg1 TNF-α 1735:1739 TNF-α 1735:1739 TNF-α 1735:1739 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 13 40 theme necrosis 1716:1723 arg1 factor-α 1725:1732 tumour necrosis factor-α 1709:1732 tumour necrosis factor-α (TNF-α) 1709:1740 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 14 41 theme potential 1986:1994 arg1 PFRAAB 1920:1925 Conclusion PFRAAB 1909:1925 Conclusion PFRAAB 1909:1925 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 14 41 theme potential 1986:1994 arg1 resource 1996:2003 a potential resource 1984:2003 a potential resource for immune-enhancing drugs 1984:2030 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 11 42 theme water-soluble 1253:1265 arg1 PFRAAB 1267:1272 A water-soluble PFRAAB 1251:1272 A water-soluble PFRAAB 1251:1272 Results A water-soluble PFRAAB was obtained with a molecular weight of 115 kDa and was mainly composed of arabinose (ara), galactose (gal), glucose (glc), and mannose (man). 36124017 12 43 dep significantly 1456:1468 arg1 < 1473:1473 p < 0.05 or p < 0.01 1471:1490 < 1473:1473 Compared with CCP-induced mice, PFRAAB significantly (p < 0.05 or p < 0.01) increased the spleen and thymus index, ameliorated injury to the spleen and thymus, and evaluated immunoglobulin levels. 36124017 12 43 dep significantly 1456:1468 arg1 < 1485:1485 p < 0.05 or p < 0.01 1471:1490 < 1485:1485 Compared with CCP-induced mice, PFRAAB significantly (p < 0.05 or p < 0.01) increased the spleen and thymus index, ameliorated injury to the spleen and thymus, and evaluated immunoglobulin levels. 36124017 13 44 theme factor 1848:1853 arg1 P65 1871:1873 nuclear factor kappa-B (NF-κB) P65 1840:1873 nuclear factor kappa-B (NF-κB) P65 1840:1873 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 10 45 theme PFRAAB 1152:1157 arg1 stimulation 1137:1147 The immune stimulation 1126:1147 The immune stimulation of PFRAAB 1126:1157 The immune stimulation of PFRAAB was investigated by using cyclophosphamide- (CCP-) treated mice and RAW264.7 cells. 36124017 9 46 theme permeation 1027:1036 arg1 HPGPC 1054:1058 HPGPC 1054:1058 HPGPC 1054:1058 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 9 46 theme permeation 1027:1036 arg1 chromatography 1038:1051 high-performance gel permeation chromatography 1006:1051 high-performance gel permeation chromatography (HPGPC) 1006:1059 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 2 47 theme Bge 201:203 arg1 roots 166:170 The fibrous roots 154:170 The fibrous roots of Anemarrhena asphodeloides Bge 154:203 Background The fibrous roots of Anemarrhena asphodeloides Bge. 36124017 15 48 theme resources 2158:2166 arg1 development 2101:2111 the comprehensive development 2083:2111 the comprehensive development of Anemarrhena asphodeloides medicinal plant resources 2083:2166 Our present study provides a scientific basis for the comprehensive development of Anemarrhena asphodeloides medicinal plant resources. 36124017 4 49 theme metabolic 311:319 arg1 molecules 327:335 secondary metabolic small molecules 301:335 secondary metabolic small molecules in FRAAB 301:344 Some studies have revealed secondary metabolic small molecules in FRAAB, but there are few reports on the polysaccharides of FRAAB (PFRAAB). 36124017 6 50 theme immune 533:538 arg1 stimulation 540:550 immune stimulation 533:550 immune stimulation of PFRAAB 533:560 The present study aimed to investigate the preliminary characterization and underlying mechanism of immune stimulation of PFRAAB. 36124017 7 51 theme diethylaminoethyl-52 712:731 arg1 column 769:774 a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column 710:774 a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column 710:774 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 15 52 theme scientific 2062:2071 arg1 basis 2073:2077 a scientific basis 2060:2077 a scientific basis for the comprehensive development of Anemarrhena asphodeloides medicinal plant resources 2060:2166 Our present study provides a scientific basis for the comprehensive development of Anemarrhena asphodeloides medicinal plant resources. 36124017 6 53 theme present 437:443 arg1 study 445:449 The present study 433:449 The present study 433:449 The present study aimed to investigate the preliminary characterization and underlying mechanism of immune stimulation of PFRAAB. 36124017 15 54 theme Anemarrhena 2116:2126 arg1 resources 2158:2166 Anemarrhena asphodeloides medicinal plant resources 2116:2166 Anemarrhena asphodeloides medicinal plant resources 2116:2166 Our present study provides a scientific basis for the comprehensive development of Anemarrhena asphodeloides medicinal plant resources. 36124017 13 55 theme P65 1884:1886 arg1 expression 1790:1799 the expression 1786:1799 the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α 1786:1906 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 13 56 theme oxide 1673:1677 arg1 secretion 1653:1661 the secretion 1649:1661 the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells 1649:1768 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 6 57 dep characterization 488:503 arg1 the 472:474 the 472:474 the 472:474 The present study aimed to investigate the preliminary characterization and underlying mechanism of immune stimulation of PFRAAB. 36124017 6 58 theme preliminary 476:486 arg1 characterization 488:503 preliminary characterization 476:503 preliminary characterization 476:503 The present study aimed to investigate the preliminary characterization and underlying mechanism of immune stimulation of PFRAAB. 36124017 3 59 theme rhizome 236:242 arg1 byproducts 218:227 byproducts 218:227 byproducts of the rhizome of Anemarrhena asphodeloides 218:271 (FRAAB) are byproducts of the rhizome of Anemarrhena asphodeloides. 36124017 7 60 theme cellulose 743:751 arg1 column 769:774 a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column 710:774 a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column 710:774 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 12 61 dep spleen 1507:1512 arg1 the 1503:1505 the 1503:1505 the 1503:1505 Compared with CCP-induced mice, PFRAAB significantly (p < 0.05 or p < 0.01) increased the spleen and thymus index, ameliorated injury to the spleen and thymus, and evaluated immunoglobulin levels. 36124017 13 62 theme toll-like 1804:1812 arg1 receptor 1814:1821 toll-like receptor 4 1804:1823 toll-like receptor 4 (TLR4) 1804:1830 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 13 62 theme toll-like 1804:1812 arg1 TLR4 1826:1829 TLR4 1826:1829 TLR4 1826:1829 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 14 63 theme stimulation 1944:1954 arg1 activity 1956:1963 immune stimulation activity 1937:1963 immune stimulation activity 1937:1963 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 9 64 theme PFRAAB 982:987 arg1 composition 967:977 composition 967:977 composition 967:977 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 9 64 theme PFRAAB 982:987 arg1 weight 956:961 The molecular weight 942:961 The molecular weight 942:961 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 13 65 theme IL-6 1747:1750 arg1 secretion 1653:1661 the secretion 1649:1661 the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells 1649:1768 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 3 66 theme Anemarrhena 247:257 arg1 asphodeloides 259:271 Anemarrhena asphodeloides 247:271 Anemarrhena asphodeloides 247:271 (FRAAB) are byproducts of the rhizome of Anemarrhena asphodeloides. 36124017 9 67 theme high-performance 1006:1021 arg1 HPGPC 1054:1058 HPGPC 1054:1058 HPGPC 1054:1058 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 9 67 theme high-performance 1006:1021 arg1 chromatography 1038:1051 high-performance gel permeation chromatography 1006:1051 high-performance gel permeation chromatography (HPGPC) 1006:1059 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 7 68 theme alcohol 660:666 arg1 precipitation 668:680 alcohol precipitation 660:680 alcohol precipitation 660:680 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 13 69 theme factor-α 1725:1732 arg1 secretion 1653:1661 the secretion 1649:1661 the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells 1649:1768 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 10 70 theme RAW264.7 1227:1234 arg1 cells 1236:1240 RAW264.7 cells 1227:1240 RAW264.7 cells 1227:1240 The immune stimulation of PFRAAB was investigated by using cyclophosphamide- (CCP-) treated mice and RAW264.7 cells. 36124017 7 71 theme hot 635:637 arg1 extraction 645:654 hot water extraction 635:654 hot water extraction 635:654 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 8 72 theme PFRAAB 844:849 arg1 characterization 824:839 The preliminary characterization 808:839 The preliminary characterization of PFRAAB 808:849 The preliminary characterization of PFRAAB was studied by ultraviolet (UV) scanning and Fourier Transform Infrared Reflection (FTIR). 36124017 8 73 dep Reflection 923:932 arg1 Infrared 914:921 Infrared 914:921 Infrared 914:921 The preliminary characterization of PFRAAB was studied by ultraviolet (UV) scanning and Fourier Transform Infrared Reflection (FTIR). 36124017 8 73 dep Reflection 923:932 arg1 FTIR 935:938 FTIR 935:938 FTIR 935:938 The preliminary characterization of PFRAAB was studied by ultraviolet (UV) scanning and Fourier Transform Infrared Reflection (FTIR). 36124017 13 74 theme IKB-α 1889:1893 arg1 expression 1790:1799 the expression 1786:1799 the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α 1786:1906 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 14 75 theme Conclusion 1909:1918 arg1 PFRAAB 1920:1925 Conclusion PFRAAB 1909:1925 Conclusion PFRAAB 1909:1925 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 14 75 theme Conclusion 1909:1918 arg1 resource 1996:2003 a potential resource 1984:2003 a potential resource for immune-enhancing drugs 1984:2030 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 14 76 contain possesses 1927:1935 arg1 PFRAAB 1920:1925 Conclusion PFRAAB 1909:1925 Conclusion PFRAAB 1909:1925 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 14 76 contain possesses 1927:1935 arg1 resource 1996:2003 a potential resource 1984:2003 a potential resource for immune-enhancing drugs 1984:2030 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 14 76 contain possesses 1927:1935 arg2 activity 1956:1963 immune stimulation activity 1937:1963 immune stimulation activity 1937:1963 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 9 77 theme high-performance 1065:1080 arg1 chromatography 1089:1102 high-performance liquid chromatography 1065:1102 high-performance liquid chromatography (HPLC) 1065:1109 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 9 77 theme high-performance 1065:1080 arg1 HPLC 1105:1108 HPLC 1105:1108 HPLC 1105:1108 The molecular weight and composition of PFRAAB were analysed by high-performance gel permeation chromatography (HPGPC) and high-performance liquid chromatography (HPLC), respectively. 36124017 7 78 theme FRAAB 613:617 arg1 polysaccharide 595:608 The crude polysaccharide 585:608 The crude polysaccharide of FRAAB 585:617 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 8 79 theme ultraviolet 866:876 arg1 scanning 883:890 ultraviolet (UV) scanning 866:890 ultraviolet (UV) scanning 866:890 The preliminary characterization of PFRAAB was studied by ultraviolet (UV) scanning and Fourier Transform Infrared Reflection (FTIR). 36124017 11 80 theme 115 kDa 1314:1320 arg1 weight 1304:1309 a molecular weight 1292:1309 a molecular weight of 115 kDa 1292:1320 Results A water-soluble PFRAAB was obtained with a molecular weight of 115 kDa and was mainly composed of arabinose (ara), galactose (gal), glucose (glc), and mannose (man). 36124017 0 81 theme Water-Soluble 2:14 arg1 Polysaccharide 16:29 A Water-Soluble Polysaccharide 0:29 A Water-Soluble Polysaccharide from the Fibrous Root of Anemarrhena 0:66 A Water-Soluble Polysaccharide from the Fibrous Root of Anemarrhena asphodeloides Bge. 36124017 13 82 from secretion 1653:1661 arg1 cells 1764:1768 RAW264.7 cells 1755:1768 RAW264.7 cells 1755:1768 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 8 83 theme UV 879:880 arg1 scanning 883:890 ultraviolet (UV) scanning 866:890 ultraviolet (UV) scanning 866:890 The preliminary characterization of PFRAAB was studied by ultraviolet (UV) scanning and Fourier Transform Infrared Reflection (FTIR). 36124017 10 84 theme immune 1130:1135 arg1 stimulation 1137:1147 The immune stimulation 1126:1147 The immune stimulation of PFRAAB 1126:1157 The immune stimulation of PFRAAB was investigated by using cyclophosphamide- (CCP-) treated mice and RAW264.7 cells. 36124017 1 85 theme Immune 95:100 arg1 Effect 114:119 Its Immune Enhancement Effect 91:119 Its Immune Enhancement Effect in Vivo and in Vitro 91:140 and Its Immune Enhancement Effect in Vivo and in Vitro. 36124017 13 86 theme tumour 1709:1714 arg1 TNF-α 1735:1739 TNF-α 1735:1739 TNF-α 1735:1739 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 13 86 theme tumour 1709:1714 arg1 factor-α 1725:1732 tumour necrosis factor-α 1709:1732 tumour necrosis factor-α (TNF-α) 1709:1740 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 0 87 theme Fibrous 40:46 arg1 Root 48:51 the Fibrous Root 36:51 the Fibrous Root of Anemarrhena 36:66 A Water-Soluble Polysaccharide from the Fibrous Root of Anemarrhena asphodeloides Bge. 36124017 7 88 theme dialysis 789:796 arg1 membrane 798:805 graphene dialysis membrane 780:805 graphene dialysis membrane 780:805 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 12 89 theme CCP-induced 1431:1441 arg1 mice 1443:1446 CCP-induced mice 1431:1446 CCP-induced mice 1431:1446 Compared with CCP-induced mice, PFRAAB significantly (p < 0.05 or p < 0.01) increased the spleen and thymus index, ameliorated injury to the spleen and thymus, and evaluated immunoglobulin levels. 36124017 6 90 theme PFRAAB 555:560 arg1 stimulation 540:550 immune stimulation 533:550 immune stimulation of PFRAAB 533:560 The present study aimed to investigate the preliminary characterization and underlying mechanism of immune stimulation of PFRAAB. 36124017 2 91 theme fibrous 158:164 arg1 roots 166:170 The fibrous roots 154:170 The fibrous roots of Anemarrhena asphodeloides Bge 154:203 Background The fibrous roots of Anemarrhena asphodeloides Bge. 36124017 15 92 theme medicinal 2142:2150 arg1 resources 2158:2166 Anemarrhena asphodeloides medicinal plant resources 2116:2166 Anemarrhena asphodeloides medicinal plant resources 2116:2166 Our present study provides a scientific basis for the comprehensive development of Anemarrhena asphodeloides medicinal plant resources. 36124017 13 93 theme nuclear 1840:1846 arg1 P65 1871:1873 nuclear factor kappa-B (NF-κB) P65 1840:1873 nuclear factor kappa-B (NF-κB) P65 1840:1873 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 14 94 used used 1976:1979 arg2 PFRAAB 1920:1925 Conclusion PFRAAB 1909:1925 Conclusion PFRAAB 1909:1925 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 14 94 used used 1976:1979 arg2 resource 1996:2003 a potential resource 1984:2003 a potential resource for immune-enhancing drugs 1984:2030 Conclusion PFRAAB possesses immune stimulation activity and can be used as a potential resource for immune-enhancing drugs. 36124017 13 95 theme P65 1871:1873 arg1 expression 1790:1799 the expression 1786:1799 the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α 1786:1906 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 7 96 dep Materials 563:571 arg1 obtained 623:630 obtained 623:630 was obtained by hot water extraction and alcohol precipitation 619:680 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 13 97 theme kappa-B 1855:1861 arg1 P65 1871:1873 nuclear factor kappa-B (NF-κB) P65 1840:1873 nuclear factor kappa-B (NF-κB) P65 1840:1873 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 7 98 theme chromatographic 753:767 arg1 column 769:774 a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column 710:774 a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column 710:774 Materials and Methods The crude polysaccharide of FRAAB was obtained by hot water extraction and alcohol precipitation, and PFRAAB was purified by a diethylaminoethyl-52 (DEAE-52) cellulose chromatographic column and graphene dialysis membrane. 36124017 10 99 theme cyclophosphamide- 1185:1201 arg1 mice 1218:1221 cyclophosphamide- (CCP-) treated mice 1185:1221 cyclophosphamide- (CCP-) treated mice 1185:1221 The immune stimulation of PFRAAB was investigated by using cyclophosphamide- (CCP-) treated mice and RAW264.7 cells. 36124017 4 100 theme secondary 301:309 arg1 molecules 327:335 secondary metabolic small molecules 301:335 secondary metabolic small molecules in FRAAB 301:344 Some studies have revealed secondary metabolic small molecules in FRAAB, but there are few reports on the polysaccharides of FRAAB (PFRAAB). 36124017 13 101 theme interleukin-1β 1685:1698 arg1 secretion 1653:1661 the secretion 1649:1661 the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells 1649:1768 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 13 102 theme Myd88 1833:1837 arg1 expression 1790:1799 the expression 1786:1799 the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α 1786:1906 In addition, PFRAAB also increased the secretion of nitric oxide (NO), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and IL-6 in RAW264.7 cells and upregulated the expression of toll-like receptor 4 (TLR4), Myd88, nuclear factor kappa-B (NF-κB) P65, p-NF-κB P65, IKB-α, and p-IKB-α. 36124017 15 103 theme plant 2152:2156 arg1 resources 2158:2166 Anemarrhena asphodeloides medicinal plant resources 2116:2166 Anemarrhena asphodeloides medicinal plant resources 2116:2166 Our present study provides a scientific basis for the comprehensive development of Anemarrhena asphodeloides medicinal plant resources. 35862663 17 0 theme comparative 2360:2370 arg1 analysis 2379:2386 comparative genome analysis 2360:2386 comparative genome analysis 2360:2386 Here, we show that two closely related members of the family Treponemataceae differ strongly in their sensitivity to high hydrogen partial pressure, and we explain the metabolic mechanisms that cause these differences by comparative genome analysis. 35862663 19 1 theme hydrogen 2714:2721 arg1 transfer 2723:2730 interspecies hydrogen transfer 2701:2730 interspecies hydrogen transfer 2701:2730 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 9 2 theme partial 1119:1125 arg1 pressures 1127:1135 high H2 partial pressures 1111:1135 high H2 partial pressures 1111:1135 In contrast to the growth of T. zuelzerae, that of strain RmG11 was strongly inhibited at high H2 partial pressures but improved considerably when H2 was removed from the headspace. 35862663 18 3 from growth 2426:2431 arg1 products 2498:2505 its fermentation products 2481:2505 its fermentation products 2481:2505 We demonstrate a strong boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen. 35862663 12 4 theme genomic 1740:1746 arg1 potential 1748:1756 the genomic potential 1736:1756 the genomic potential to degrade other plant polysaccharides 1736:1795 In addition, we found that T. zuelzerae utilizes xylan and possesses the genomic potential to degrade other plant polysaccharides. 35862663 11 5 contain possesses 1379:1387 arg2 hydrogenase 1426:1436 only a single, electron-confurcating hydrogenase 1389:1436 only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex 1389:1664 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 11 5 contain possesses 1379:1387 arg1 RmG11 1373:1377 strain RmG11 1366:1377 strain RmG11 1366:1377 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 5 6 theme only 493:496 arg1 zuelzerae 545:553 Treponema zuelzerae 535:553 Treponema zuelzerae 535:553 The only cultivated representative to date is Treponema zuelzerae, isolated from freshwater mud. 35862663 5 6 theme only 493:496 arg1 representative 509:522 The only cultivated representative 489:522 The only cultivated representative to date 489:530 The only cultivated representative to date is Treponema zuelzerae, isolated from freshwater mud. 35862663 18 7 from shift 2472:2476 arg1 products 2498:2505 its fermentation products 2481:2505 its fermentation products 2481:2505 We demonstrate a strong boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen. 35862663 3 8 theme Most 236:239 arg1 members 241:247 Most members 236:247 Most members of the family Treponemataceae (Spirochaetales) 236:294 Most members of the family Treponemataceae (Spirochaetales) are associated with vertebrate hosts. 35862663 11 9 theme Rnf 1654:1656 arg1 complex 1658:1664 the Rnf complex 1650:1664 the Rnf complex 1650:1664 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 11 10 from formation 1614:1622 arg1 ferredoxin 1635:1644 ferredoxin 1635:1644 ferredoxin 1635:1644 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 4 11 theme diverse 345:351 arg1 present 451:457 present 451:457 present 451:457 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 4 11 theme diverse 345:351 arg1 clade 353:357 a diverse clade 343:357 a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages 343:446 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 3 12 theme family 256:261 arg1 Spirochaetales 280:293 Spirochaetales 280:293 Spirochaetales 280:293 Most members of the family Treponemataceae (Spirochaetales) are associated with vertebrate hosts. 35862663 3 12 theme family 256:261 arg1 Treponemataceae 263:277 the family Treponemataceae 252:277 the family Treponemataceae (Spirochaetales) 252:294 Most members of the family Treponemataceae (Spirochaetales) are associated with vertebrate hosts. 35862663 8 13 theme small 988:992 arg1 H2 1017:1018 H2 1017:1018 H2 1017:1018 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 13 theme small 988:992 arg1 acetate 1005:1011 acetate 1005:1011 acetate 1005:1011 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 13 theme small 988:992 arg1 amounts 994:1000 only small amounts 983:1000 only small amounts of acetate and H2 983:1018 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 19 14 theme interspecies 2701:2712 arg1 transfer 2723:2730 interspecies hydrogen transfer 2701:2730 interspecies hydrogen transfer 2701:2730 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 7 15 theme novel 700:704 arg1 lineage 718:724 a novel genus-level lineage 698:724 a novel genus-level lineage of Treponemataceae 698:743 The strain represents a novel genus-level lineage of Treponemataceae and is metabolically distinct from T. zuelzerae. 35862663 13 16 theme phylogenomic 1822:1833 arg1 evidence 1835:1842 phenotypic and phylogenomic evidence 1807:1842 phenotypic and phylogenomic evidence 1807:1842 Based on phenotypic and phylogenomic evidence, we describe strain RmG11 as Brucepastera parasyntrophica gen. nov., sp. 35862663 18 17 with cocultivation 2525:2537 arg1 methanogen 2559:2568 a H2-utilizing methanogen 2544:2568 a H2-utilizing methanogen 2544:2568 We demonstrate a strong boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen. 35862663 11 18 theme genomic 1335:1341 arg1 analysis 1343:1350 Comparative genomic analysis 1323:1350 Comparative genomic analysis 1323:1350 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 1 19 dep nov. 68:71 arg1 nov. 103:106 zuelzerae gen. nov. 88:106 nov. and Teretinema zuelzerae gen. nov. 68:106 nov. and Teretinema zuelzerae gen. nov., comb. 35862663 8 20 theme various 827:833 arg1 sugars 835:840 various sugars 827:840 various sugars 827:840 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 17 21 theme metabolic 2307:2315 arg1 mechanisms 2317:2326 the metabolic mechanisms 2303:2326 the metabolic mechanisms that cause these differences by comparative genome analysis 2303:2386 Here, we show that two closely related members of the family Treponemataceae differ strongly in their sensitivity to high hydrogen partial pressure, and we explain the metabolic mechanisms that cause these differences by comparative genome analysis. 35862663 9 22 attach removed 1175:1181 arg2 H2 1168:1169 H2 1168:1169 H2 1168:1169 In contrast to the growth of T. zuelzerae, that of strain RmG11 was strongly inhibited at high H2 partial pressures but improved considerably when H2 was removed from the headspace. 35862663 9 22 attach removed 1175:1181 arg1 headspace 1192:1200 the headspace 1188:1200 the headspace 1188:1200 In contrast to the growth of T. zuelzerae, that of strain RmG11 was strongly inhibited at high H2 partial pressures but improved considerably when H2 was removed from the headspace. 35862663 12 23 contain possesses 1726:1734 arg2 potential 1748:1756 the genomic potential 1736:1756 the genomic potential to degrade other plant polysaccharides 1736:1795 In addition, we found that T. zuelzerae utilizes xylan and possesses the genomic potential to degrade other plant polysaccharides. 35862663 12 23 contain possesses 1726:1734 arg1 zuelzerae 1697:1705 T. zuelzerae 1694:1705 T. zuelzerae 1694:1705 In addition, we found that T. zuelzerae utilizes xylan and possesses the genomic potential to degrade other plant polysaccharides. 35862663 3 24 theme vertebrate 316:325 arg1 hosts 327:331 vertebrate hosts 316:331 vertebrate hosts 316:331 Most members of the family Treponemataceae (Spirochaetales) are associated with vertebrate hosts. 35862663 4 25 theme genus-level 427:437 arg1 lineages 439:446 several genus-level lineages 419:446 several genus-level lineages 419:446 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 19 26 from importance 2687:2696 arg1 interactions 2761:2772 not-obligately-syntrophic interactions 2735:2772 not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments 2735:2842 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 2 27 theme Spirochetes 223:233 arg1 Metabolism 209:218 the Energy Metabolism 198:218 the Energy Metabolism of Spirochetes 198:233 nov. (Treponemataceae) Reveals the Importance of Interspecies Hydrogen Transfer in the Energy Metabolism of Spirochetes. 35862663 16 28 theme molecular 2087:2095 arg1 hydrogen 2097:2104 molecular hydrogen 2087:2104 molecular hydrogen as a major fermentation product 2087:2136 IMPORTANCE Spirochetes are widely distributed in various anoxic environments and commonly form molecular hydrogen as a major fermentation product. 35862663 6 29 theme RmG11 628:632 arg1 isolation 608:616 the isolation 604:616 the isolation of strain RmG11 from the intestinal tract of cockroaches 604:673 Here, we describe the isolation of strain RmG11 from the intestinal tract of cockroaches. 35862663 18 30 theme fermentation 2485:2496 arg1 products 2498:2505 its fermentation products 2481:2505 its fermentation products 2481:2505 We demonstrate a strong boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen. 35862663 17 31 theme related 2170:2176 arg1 members 2178:2184 two closely related members 2158:2184 two closely related members of the family Treponemataceae 2158:2214 Here, we show that two closely related members of the family Treponemataceae differ strongly in their sensitivity to high hydrogen partial pressure, and we explain the metabolic mechanisms that cause these differences by comparative genome analysis. 35862663 8 32 theme major 869:873 arg1 acetate 851:857 acetate 851:857 acetate 851:857 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 32 theme major 869:873 arg1 products 888:895 major fermentation products 869:895 major fermentation products 869:895 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 32 theme major 869:873 arg1 H2 863:864 H2 863:864 H2 863:864 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 4 33 theme anoxic 468:473 arg1 environments 475:486 other anoxic environments 462:486 other anoxic environments 462:486 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 16 34 theme major 2111:2115 arg1 product 2130:2136 a major fermentation product 2109:2136 a major fermentation product 2109:2136 IMPORTANCE Spirochetes are widely distributed in various anoxic environments and commonly form molecular hydrogen as a major fermentation product. 35862663 13 35 theme strain 1857:1862 arg1 RmG11 1864:1868 strain RmG11 1857:1868 strain RmG11 1857:1868 Based on phenotypic and phylogenomic evidence, we describe strain RmG11 as Brucepastera parasyntrophica gen. nov., sp. 35862663 17 36 theme family 2193:2198 arg1 Treponemataceae 2200:2214 the family Treponemataceae 2189:2214 the family Treponemataceae 2189:2214 Here, we show that two closely related members of the family Treponemataceae differ strongly in their sensitivity to high hydrogen partial pressure, and we explain the metabolic mechanisms that cause these differences by comparative genome analysis. 35862663 10 37 theme RmG11 1224:1228 arg1 Cocultures 1203:1212 Cocultures 1203:1212 Cocultures of strain RmG11 with the H2-consuming Methanospirillum hungatei 1203:1276 Cocultures of strain RmG11 with the H2-consuming Methanospirillum hungatei produced acetate and methane but no ethanol. 35862663 0 38 theme Comparative 0:10 arg1 Analysis 12:19 Comparative Analysis 0:19 Comparative Analysis of Brucepastera 0:35 Comparative Analysis of Brucepastera parasyntrophica gen. nov., sp. 35862663 1 39 theme zuelzerae 88:96 arg1 nov. 103:106 zuelzerae gen. nov. 88:106 nov. and Teretinema zuelzerae gen. nov. 68:106 nov. and Teretinema zuelzerae gen. nov., comb. 35862663 8 40 theme strain 898:903 arg1 RmG11 905:909 strain RmG11 898:909 strain RmG11 898:909 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 18 41 theme strain 2459:2464 arg1 shift 2472:2476 a shift 2470:2476 a shift in its fermentation products to acetate 2470:2516 We demonstrate a strong boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen. 35862663 18 41 theme strain 2459:2464 arg1 growth 2426:2431 the growth 2422:2431 the growth of the hydrogen-sensitive strain 2422:2464 We demonstrate a strong boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen. 35862663 6 42 theme cockroaches 663:673 arg1 tract 654:658 the intestinal tract 639:658 the intestinal tract of cockroaches 639:673 Here, we describe the isolation of strain RmG11 from the intestinal tract of cockroaches. 35862663 16 43 theme various 2041:2047 arg1 environments 2056:2067 various anoxic environments 2041:2067 various anoxic environments 2041:2067 IMPORTANCE Spirochetes are widely distributed in various anoxic environments and commonly form molecular hydrogen as a major fermentation product. 35862663 10 44 theme Methanospirillum 1252:1267 arg1 hungatei 1269:1276 the H2-consuming Methanospirillum hungatei 1235:1276 the H2-consuming Methanospirillum hungatei 1235:1276 Cocultures of strain RmG11 with the H2-consuming Methanospirillum hungatei produced acetate and methane but no ethanol. 35862663 14 45 dep nov. 1917:1920 arg1 comb 1981:1984 comb 1981:1984 comb 1981:1984 nov. and Treponema zuelzerae as Teretinema zuelzerae gen. nov., comb. 35862663 14 45 dep nov. 1917:1920 arg1 nov. 1975:1978 Teretinema zuelzerae gen. nov. 1949:1978 Teretinema zuelzerae gen. nov. 1949:1978 nov. and Treponema zuelzerae as Teretinema zuelzerae gen. nov., comb. 35862663 14 46 theme gen. 1970:1973 arg1 comb 1981:1984 comb 1981:1984 comb 1981:1984 nov. and Treponema zuelzerae as Teretinema zuelzerae gen. nov., comb. 35862663 14 46 theme gen. 1970:1973 arg1 nov. 1975:1978 Teretinema zuelzerae gen. nov. 1949:1978 Teretinema zuelzerae gen. nov. 1949:1978 nov. and Treponema zuelzerae as Teretinema zuelzerae gen. nov., comb. 35862663 14 47 theme Teretinema 1949:1958 arg1 comb 1981:1984 comb 1981:1984 comb 1981:1984 nov. and Treponema zuelzerae as Teretinema zuelzerae gen. nov., comb. 35862663 14 47 theme Teretinema 1949:1958 arg1 nov. 1975:1978 Teretinema zuelzerae gen. nov. 1949:1978 Teretinema zuelzerae gen. nov. 1949:1978 nov. and Treponema zuelzerae as Teretinema zuelzerae gen. nov., comb. 35862663 2 48 theme Transfer 186:193 arg1 Importance 150:159 the Importance 146:159 the Importance of Interspecies Hydrogen Transfer in the Energy Metabolism of Spirochetes 146:233 nov. (Treponemataceae) Reveals the Importance of Interspecies Hydrogen Transfer in the Energy Metabolism of Spirochetes. 35862663 19 49 theme not-obligately-syntrophic 2735:2759 arg1 interactions 2761:2772 not-obligately-syntrophic interactions 2735:2772 not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments 2735:2842 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 10 50 theme strain 1217:1222 arg1 RmG11 1224:1228 strain RmG11 1217:1228 strain RmG11 1217:1228 Cocultures of strain RmG11 with the H2-consuming Methanospirillum hungatei produced acetate and methane but no ethanol. 35862663 12 51 theme plant 1775:1779 arg1 polysaccharides 1781:1795 other plant polysaccharides 1769:1795 other plant polysaccharides 1769:1795 In addition, we found that T. zuelzerae utilizes xylan and possesses the genomic potential to degrade other plant polysaccharides. 35862663 5 52 attach isolated 556:563 arg1 mud 581:583 freshwater mud 570:583 freshwater mud 570:583 The only cultivated representative to date is Treponema zuelzerae, isolated from freshwater mud. 35862663 5 52 attach isolated 556:563 arg2 representative 509:522 The only cultivated representative 489:522 The only cultivated representative to date 489:530 The only cultivated representative to date is Treponema zuelzerae, isolated from freshwater mud. 35862663 5 52 attach isolated 556:563 arg2 zuelzerae 545:553 Treponema zuelzerae 535:553 Treponema zuelzerae 535:553 The only cultivated representative to date is Treponema zuelzerae, isolated from freshwater mud. 35862663 2 53 theme Interspecies 164:175 arg1 Transfer 186:193 Interspecies Hydrogen Transfer 164:193 Interspecies Hydrogen Transfer 164:193 nov. (Treponemataceae) Reveals the Importance of Interspecies Hydrogen Transfer in the Energy Metabolism of Spirochetes. 35862663 11 54 theme H2 1627:1628 arg1 formation 1614:1622 the thermodynamically more favorable formation 1577:1622 the thermodynamically more favorable formation of H2 from ferredoxin 1577:1644 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 19 55 theme anoxic 2824:2829 arg1 environments 2831:2842 anoxic environments 2824:2842 anoxic environments 2824:2842 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 13 56 theme phenotypic 1807:1816 arg1 evidence 1835:1842 phenotypic and phylogenomic evidence 1807:1842 phenotypic and phylogenomic evidence 1807:1842 Based on phenotypic and phylogenomic evidence, we describe strain RmG11 as Brucepastera parasyntrophica gen. nov., sp. 35862663 9 57 theme H2 1116:1117 arg1 pressures 1127:1135 high H2 partial pressures 1111:1135 high H2 partial pressures 1111:1135 In contrast to the growth of T. zuelzerae, that of strain RmG11 was strongly inhibited at high H2 partial pressures but improved considerably when H2 was removed from the headspace. 35862663 18 58 dep strong 2406:2411 arg1 boost 2413:2417 boost 2413:2417 boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen 2413:2568 We demonstrate a strong boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen. 35862663 7 59 theme Treponemataceae 729:743 arg1 lineage 718:724 a novel genus-level lineage 698:724 a novel genus-level lineage of Treponemataceae 698:743 The strain represents a novel genus-level lineage of Treponemataceae and is metabolically distinct from T. zuelzerae. 35862663 2 60 from Importance 150:159 arg1 Metabolism 209:218 the Energy Metabolism 198:218 the Energy Metabolism of Spirochetes 198:233 nov. (Treponemataceae) Reveals the Importance of Interspecies Hydrogen Transfer in the Energy Metabolism of Spirochetes. 35862663 7 61 from zuelzerae 783:791 arg1 strain 680:685 The strain 676:685 The strain 676:685 The strain represents a novel genus-level lineage of Treponemataceae and is metabolically distinct from T. zuelzerae. 35862663 7 61 from zuelzerae 783:791 arg1 distinct 766:773 distinct 766:773 distinct 766:773 The strain represents a novel genus-level lineage of Treponemataceae and is metabolically distinct from T. zuelzerae. 35862663 17 62 theme genome 2372:2377 arg1 analysis 2379:2386 comparative genome analysis 2360:2386 comparative genome analysis 2360:2386 Here, we show that two closely related members of the family Treponemataceae differ strongly in their sensitivity to high hydrogen partial pressure, and we explain the metabolic mechanisms that cause these differences by comparative genome analysis. 35862663 11 63 theme second 1524:1529 arg1 hydrogenase 1553:1563 a second, ferredoxin-dependent hydrogenase 1522:1563 a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex 1522:1664 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 4 64 theme treponemes 397:406 arg1 present 451:457 present 451:457 present 451:457 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 4 64 theme treponemes 397:406 arg1 clade 353:357 a diverse clade 343:357 a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages 343:446 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 13 65 theme parasyntrophica 1886:1900 arg1 sp 1913:1914 sp 1913:1914 sp 1913:1914 Based on phenotypic and phylogenomic evidence, we describe strain RmG11 as Brucepastera parasyntrophica gen. nov., sp. 35862663 13 65 theme parasyntrophica 1886:1900 arg1 nov. 1907:1910 Brucepastera parasyntrophica gen. nov. 1873:1910 Brucepastera parasyntrophica gen. nov. 1873:1910 Based on phenotypic and phylogenomic evidence, we describe strain RmG11 as Brucepastera parasyntrophica gen. nov., sp. 35862663 5 66 theme cultivated 498:507 arg1 zuelzerae 545:553 Treponema zuelzerae 535:553 Treponema zuelzerae 535:553 The only cultivated representative to date is Treponema zuelzerae, isolated from freshwater mud. 35862663 5 66 theme cultivated 498:507 arg1 representative 509:522 The only cultivated representative 489:522 The only cultivated representative to date 489:530 The only cultivated representative to date is Treponema zuelzerae, isolated from freshwater mud. 35862663 4 67 located present 451:457 arg2 present 451:457 present 451:457 present 451:457 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 4 67 located present 451:457 arg1 environments 475:486 other anoxic environments 462:486 other anoxic environments 462:486 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 4 67 located present 451:457 arg2 clade 353:357 a diverse clade 343:357 a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages 343:446 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 4 68 from environments 475:486 arg1 present 451:457 present 451:457 present 451:457 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 4 68 from environments 475:486 arg1 clade 353:357 a diverse clade 343:357 a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages 343:446 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 19 69 theme hydrogenotrophic 2797:2812 arg1 guilds 2814:2819 fermentative and hydrogenotrophic guilds 2780:2819 fermentative and hydrogenotrophic guilds in anoxic environments 2780:2842 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 4 70 theme uncultured 362:371 arg1 treponemes 397:406 uncultured, putatively free-living treponemes 362:406 uncultured, putatively free-living treponemes 362:406 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 18 71 theme H2-utilizing 2546:2557 arg1 methanogen 2559:2568 a H2-utilizing methanogen 2544:2568 a H2-utilizing methanogen 2544:2568 We demonstrate a strong boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen. 35862663 19 72 theme transfer 2723:2730 arg1 importance 2687:2696 the importance 2683:2696 the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments 2683:2842 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 3 73 theme Treponemataceae 263:277 arg1 members 241:247 Most members 236:247 Most members of the family Treponemataceae (Spirochaetales) 236:294 Most members of the family Treponemataceae (Spirochaetales) are associated with vertebrate hosts. 35862663 11 74 theme Comparative 1323:1333 arg1 analysis 1343:1350 Comparative genomic analysis 1323:1350 Comparative genomic analysis 1323:1350 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 4 75 from present 451:457 arg1 environments 475:486 other anoxic environments 462:486 other anoxic environments 462:486 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 6 76 theme strain 621:626 arg1 RmG11 628:632 strain RmG11 621:632 strain RmG11 621:632 Here, we describe the isolation of strain RmG11 from the intestinal tract of cockroaches. 35862663 4 77 dep uncultured 362:371 arg1 free-living 385:395 free-living 385:395 free-living 385:395 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 4 78 theme other 462:466 arg1 environments 475:486 other anoxic environments 462:486 other anoxic environments 462:486 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 11 79 dep single 1396:1401 arg1 electron-confurcating 1404:1424 electron-confurcating 1404:1424 electron-confurcating 1404:1424 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 2 80 theme Energy 202:207 arg1 Metabolism 209:218 the Energy Metabolism 198:218 the Energy Metabolism of Spirochetes 198:233 nov. (Treponemataceae) Reveals the Importance of Interspecies Hydrogen Transfer in the Energy Metabolism of Spirochetes. 35862663 4 81 theme several 419:425 arg1 lineages 439:446 several genus-level lineages 419:446 several genus-level lineages 419:446 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 6 82 from tract 654:658 arg1 isolation 608:616 the isolation 604:616 the isolation of strain RmG11 from the intestinal tract of cockroaches 604:673 Here, we describe the isolation of strain RmG11 from the intestinal tract of cockroaches. 35862663 11 83 theme reduced 1466:1472 arg1 ferredoxin 1474:1483 reduced ferredoxin 1466:1483 reduced ferredoxin 1466:1483 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 5 84 theme freshwater 570:579 arg1 mud 581:583 freshwater mud 570:583 freshwater mud 570:583 The only cultivated representative to date is Treponema zuelzerae, isolated from freshwater mud. 35862663 6 85 theme intestinal 643:652 arg1 tract 654:658 the intestinal tract 639:658 the intestinal tract of cockroaches 639:673 Here, we describe the isolation of strain RmG11 from the intestinal tract of cockroaches. 35862663 13 86 theme Brucepastera 1873:1884 arg1 sp 1913:1914 sp 1913:1914 sp 1913:1914 Based on phenotypic and phylogenomic evidence, we describe strain RmG11 as Brucepastera parasyntrophica gen. nov., sp. 35862663 13 86 theme Brucepastera 1873:1884 arg1 nov. 1907:1910 Brucepastera parasyntrophica gen. nov. 1873:1910 Brucepastera parasyntrophica gen. nov. 1873:1910 Based on phenotypic and phylogenomic evidence, we describe strain RmG11 as Brucepastera parasyntrophica gen. nov., sp. 35862663 8 87 theme acetate 1005:1011 arg1 acetate 1005:1011 acetate 1005:1011 acetate 1005:1011 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 87 theme acetate 1005:1011 arg1 maltose 935:941 maltose 935:941 maltose 935:941 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 87 theme acetate 1005:1011 arg1 H2 1017:1018 H2 1017:1018 H2 1017:1018 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 87 theme acetate 1005:1011 arg1 starch 948:953 starch 948:953 starch 948:953 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 87 theme acetate 1005:1011 arg1 amounts 994:1000 only small amounts 983:1000 only small amounts of acetate and H2 983:1018 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 87 theme acetate 1005:1011 arg1 glucose 926:932 glucose 926:932 glucose 926:932 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 11 88 contain possesses 1512:1520 arg2 hydrogenase 1553:1563 a second, ferredoxin-dependent hydrogenase 1522:1563 a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex 1522:1664 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 11 88 contain possesses 1512:1520 arg1 zuelzerae 1497:1505 T. zuelzerae 1494:1505 T. zuelzerae 1494:1505 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 13 89 theme gen. 1902:1905 arg1 sp 1913:1914 sp 1913:1914 sp 1913:1914 Based on phenotypic and phylogenomic evidence, we describe strain RmG11 as Brucepastera parasyntrophica gen. nov., sp. 35862663 13 89 theme gen. 1902:1905 arg1 nov. 1907:1910 Brucepastera parasyntrophica gen. nov. 1873:1910 Brucepastera parasyntrophica gen. nov. 1873:1910 Based on phenotypic and phylogenomic evidence, we describe strain RmG11 as Brucepastera parasyntrophica gen. nov., sp. 35862663 19 90 theme unrecognized 2598:2609 arg1 facet 2611:2615 a hitherto unrecognized facet 2587:2615 a hitherto unrecognized facet 2587:2615 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 8 91 theme H2 1017:1018 arg1 acetate 1005:1011 acetate 1005:1011 acetate 1005:1011 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 91 theme H2 1017:1018 arg1 maltose 935:941 maltose 935:941 maltose 935:941 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 91 theme H2 1017:1018 arg1 H2 1017:1018 H2 1017:1018 H2 1017:1018 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 91 theme H2 1017:1018 arg1 starch 948:953 starch 948:953 starch 948:953 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 91 theme H2 1017:1018 arg1 amounts 994:1000 only small amounts 983:1000 only small amounts of acetate and H2 983:1018 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 91 theme H2 1017:1018 arg1 glucose 926:932 glucose 926:932 glucose 926:932 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 17 92 theme high 2256:2259 arg1 pressure 2278:2285 high hydrogen partial pressure 2256:2285 high hydrogen partial pressure 2256:2285 Here, we show that two closely related members of the family Treponemataceae differ strongly in their sensitivity to high hydrogen partial pressure, and we explain the metabolic mechanisms that cause these differences by comparative genome analysis. 35862663 10 93 theme H2-consuming 1239:1250 arg1 hungatei 1269:1276 the H2-consuming Methanospirillum hungatei 1235:1276 the H2-consuming Methanospirillum hungatei 1235:1276 Cocultures of strain RmG11 with the H2-consuming Methanospirillum hungatei produced acetate and methane but no ethanol. 35862663 19 94 theme spirochetes 2651:2661 arg1 metabolism 2637:2646 the fermentative metabolism 2620:2646 the fermentative metabolism of spirochetes 2620:2661 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 17 95 theme partial 2270:2276 arg1 pressure 2278:2285 high hydrogen partial pressure 2256:2285 high hydrogen partial pressure 2256:2285 Here, we show that two closely related members of the family Treponemataceae differ strongly in their sensitivity to high hydrogen partial pressure, and we explain the metabolic mechanisms that cause these differences by comparative genome analysis. 35862663 1 96 dep comb 109:112 arg1 nov. 68:71 nov. 68:71 nov. 68:71 nov. and Teretinema zuelzerae gen. nov., comb. 35862663 1 96 dep comb 109:112 arg1 Teretinema 77:86 Teretinema 77:86 Teretinema 77:86 nov. and Teretinema zuelzerae gen. nov., comb. 35862663 11 97 theme single 1396:1401 arg1 hydrogenase 1426:1436 only a single, electron-confurcating hydrogenase 1389:1436 only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex 1389:1664 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 4 98 attach present 451:457 arg2 present 451:457 present 451:457 present 451:457 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 4 98 attach present 451:457 arg1 environments 475:486 other anoxic environments 462:486 other anoxic environments 462:486 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 4 98 attach present 451:457 arg2 clade 353:357 a diverse clade 343:357 a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages 343:446 However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. 35862663 19 99 theme fermentative 2624:2635 arg1 metabolism 2637:2646 the fermentative metabolism 2620:2646 the fermentative metabolism of spirochetes 2620:2661 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 16 100 theme IMPORTANCE 1992:2001 arg1 Spirochetes 2003:2013 IMPORTANCE Spirochetes 1992:2013 IMPORTANCE Spirochetes 1992:2013 IMPORTANCE Spirochetes are widely distributed in various anoxic environments and commonly form molecular hydrogen as a major fermentation product. 35862663 8 101 theme fermentation 875:886 arg1 acetate 851:857 acetate 851:857 acetate 851:857 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 101 theme fermentation 875:886 arg1 products 888:895 major fermentation products 869:895 major fermentation products 869:895 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 8 101 theme fermentation 875:886 arg1 H2 863:864 H2 863:864 H2 863:864 While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. 35862663 17 102 theme hydrogen 2261:2268 arg1 pressure 2278:2285 high hydrogen partial pressure 2256:2285 high hydrogen partial pressure 2256:2285 Here, we show that two closely related members of the family Treponemataceae differ strongly in their sensitivity to high hydrogen partial pressure, and we explain the metabolic mechanisms that cause these differences by comparative genome analysis. 35862663 16 103 theme fermentation 2117:2128 arg1 product 2130:2136 a major fermentation product 2109:2136 a major fermentation product 2109:2136 IMPORTANCE Spirochetes are widely distributed in various anoxic environments and commonly form molecular hydrogen as a major fermentation product. 35862663 17 104 theme Treponemataceae 2200:2214 arg1 members 2178:2184 two closely related members 2158:2184 two closely related members of the family Treponemataceae 2158:2214 Here, we show that two closely related members of the family Treponemataceae differ strongly in their sensitivity to high hydrogen partial pressure, and we explain the metabolic mechanisms that cause these differences by comparative genome analysis. 35862663 9 105 theme zuelzerae 1053:1061 arg1 growth 1040:1045 the growth 1036:1045 the growth of T. zuelzerae 1036:1061 In contrast to the growth of T. zuelzerae, that of strain RmG11 was strongly inhibited at high H2 partial pressures but improved considerably when H2 was removed from the headspace. 35862663 7 106 theme genus-level 706:716 arg1 lineage 718:724 a novel genus-level lineage 698:724 a novel genus-level lineage of Treponemataceae 698:743 The strain represents a novel genus-level lineage of Treponemataceae and is metabolically distinct from T. zuelzerae. 35862663 0 107 theme Brucepastera 24:35 arg1 Analysis 12:19 Comparative Analysis 0:19 Comparative Analysis of Brucepastera 0:35 Comparative Analysis of Brucepastera parasyntrophica gen. nov., sp. 35862663 1 108 theme gen. 98:101 arg1 nov. 103:106 zuelzerae gen. nov. 88:106 nov. and Teretinema zuelzerae gen. nov. 68:106 nov. and Teretinema zuelzerae gen. nov., comb. 35862663 19 109 from guilds 2814:2819 arg1 environments 2831:2842 anoxic environments 2824:2842 anoxic environments 2824:2842 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 18 110 theme hydrogen-sensitive 2440:2457 arg1 strain 2459:2464 the hydrogen-sensitive strain 2436:2464 the hydrogen-sensitive strain 2436:2464 We demonstrate a strong boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen. 35862663 0 111 theme gen. 53:56 arg1 sp 64:65 sp 64:65 sp 64:65 Comparative Analysis of Brucepastera parasyntrophica gen. nov., sp. 35862663 0 111 theme gen. 53:56 arg1 nov. 58:61 gen. nov. 53:61 gen. nov. 53:61 Comparative Analysis of Brucepastera parasyntrophica gen. nov., sp. 35862663 11 112 from ferredoxin 1635:1644 arg1 formation 1614:1622 the thermodynamically more favorable formation 1577:1622 the thermodynamically more favorable formation of H2 from ferredoxin 1577:1644 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 9 113 theme strain 1072:1077 arg1 RmG11 1079:1083 strain RmG11 1072:1083 strain RmG11 1072:1083 In contrast to the growth of T. zuelzerae, that of strain RmG11 was strongly inhibited at high H2 partial pressures but improved considerably when H2 was removed from the headspace. 35862663 10 114 with Cocultures 1203:1212 arg1 hungatei 1269:1276 the H2-consuming Methanospirillum hungatei 1235:1276 the H2-consuming Methanospirillum hungatei 1235:1276 Cocultures of strain RmG11 with the H2-consuming Methanospirillum hungatei produced acetate and methane but no ethanol. 35862663 14 115 theme zuelzerae 1960:1968 arg1 comb 1981:1984 comb 1981:1984 comb 1981:1984 nov. and Treponema zuelzerae as Teretinema zuelzerae gen. nov., comb. 35862663 14 115 theme zuelzerae 1960:1968 arg1 nov. 1975:1978 Teretinema zuelzerae gen. nov. 1949:1978 Teretinema zuelzerae gen. nov. 1949:1978 nov. and Treponema zuelzerae as Teretinema zuelzerae gen. nov., comb. 35862663 16 116 theme anoxic 2049:2054 arg1 environments 2056:2067 various anoxic environments 2041:2067 various anoxic environments 2041:2067 IMPORTANCE Spirochetes are widely distributed in various anoxic environments and commonly form molecular hydrogen as a major fermentation product. 35862663 19 117 theme fermentative 2780:2791 arg1 guilds 2814:2819 fermentative and hydrogenotrophic guilds 2780:2819 fermentative and hydrogenotrophic guilds in anoxic environments 2780:2842 Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments. 35862663 11 118 theme favorable 1604:1612 arg1 formation 1614:1622 the thermodynamically more favorable formation 1577:1622 the thermodynamically more favorable formation of H2 from ferredoxin 1577:1644 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 2 119 theme Hydrogen 177:184 arg1 Transfer 186:193 Interspecies Hydrogen Transfer 164:193 Interspecies Hydrogen Transfer 164:193 nov. (Treponemataceae) Reveals the Importance of Interspecies Hydrogen Transfer in the Energy Metabolism of Spirochetes. 35862663 12 120 theme other 1769:1773 arg1 polysaccharides 1781:1795 other plant polysaccharides 1769:1795 other plant polysaccharides 1769:1795 In addition, we found that T. zuelzerae utilizes xylan and possesses the genomic potential to degrade other plant polysaccharides. 35862663 11 121 dep second 1524:1529 arg1 ferredoxin-dependent 1532:1551 ferredoxin-dependent 1532:1551 ferredoxin-dependent 1532:1551 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 11 122 theme strain 1366:1371 arg1 RmG11 1373:1377 strain RmG11 1366:1377 strain RmG11 1366:1377 Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. 35862663 9 123 theme high 1111:1114 arg1 pressures 1127:1135 high H2 partial pressures 1111:1135 high H2 partial pressures 1111:1135 In contrast to the growth of T. zuelzerae, that of strain RmG11 was strongly inhibited at high H2 partial pressures but improved considerably when H2 was removed from the headspace. 35039109 2 0 theme self-reported 594:606 arg1 data 614:617 4-d food diary and self-reported sleep data 575:617 data 614:617 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 6 1 theme ≥ 1012:1012 arg1 h 1020:1020 ≥ 7-< 9 h 1012:1020 ≥ 7-< 9 h 1012:1020 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 1 theme ≥ 1012:1012 arg1 duration 1002:1009 those reporting optimal sleep duration 972:1009 those reporting optimal sleep duration (≥ 7-< 9 h) 972:1021 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 2 theme total 1142:1146 arg1 energy 1168:1173 0·8 % energy 1162:1173 0·8 % energy 1162:1173 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 2 theme total 1142:1146 arg1 sugars 1093:1098 non-milk extrinsic sugars 1074:1098 non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4) 1074:1139 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 2 theme total 1142:1146 arg1 carbohydrate 1148:1159 total carbohydrate 1142:1159 total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) 1142:1193 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 0 3 from intakes 144:150 arg1 those 155:159 those 155:159 those 155:159 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 9 4 theme only 1826:1829 arg1 duration 1837:1844 only sleep duration 1826:1844 only sleep duration 1826:1844 CONCLUSIONS The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. 35039109 10 5 theme weekly 1975:1980 arg1 duration 1988:1995 adequate weekly sleep duration 1966:1995 adequate weekly sleep duration 1966:1995 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 7 6 theme social 1530:1535 arg1 jetlag 1537:1542 no social jetlag 1527:1542 no social jetlag 1527:1542 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 6 7 theme non-milk 1074:1081 arg1 intake 1240:1245 a lower non-starch polysaccharides fibre intake 1199:1245 a lower non-starch polysaccharides fibre intake 1199:1245 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 7 theme non-milk 1074:1081 arg1 energy 1114:1119 0·9 % energy 1108:1119 0·9 % energy 1108:1119 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 7 theme non-milk 1074:1081 arg1 NMES 1101:1104 NMES 1101:1104 NMES 1101:1104 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 7 theme non-milk 1074:1081 arg1 sugars 1093:1098 non-milk extrinsic sugars 1074:1098 non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4) 1074:1139 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 7 theme non-milk 1074:1081 arg1 carbohydrate 1148:1159 total carbohydrate 1142:1159 total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) 1142:1193 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 7 8 contain had 1475:1477 arg1 sleepers 1387:1394 adequate sleepers 1378:1394 adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) 1378:1473 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 7 8 contain had 1475:1477 arg2 intakes 1491:1497 lower fibre intakes 1479:1497 lower fibre intakes 1479:1497 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 7 8 contain had 1475:1477 arg1 sleepers 1436:1443 all short sleepers 1426:1443 adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) 1378:1473 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 3 9 theme free-living 706:716 arg1 population 718:727 UK free-living population 703:727 UK free-living population 703:727 SETTING UK free-living population. 35039109 0 10 theme sleep 175:179 arg1 duration 181:188 adequate sleep duration 166:188 adequate sleep duration 166:188 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 1 11 theme body 435:438 arg1 composition 440:450 body composition 435:450 body composition 435:450 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 5 12 theme short 812:816 arg1 h 832:832 < 7 h 828:832 < 7 h 828:832 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 5 12 theme short 812:816 arg1 sleepers 818:825 short sleepers 812:825 short sleepers (< 7 h) 812:833 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 10 13 from impact 2053:2058 arg1 choices 2094:2100 food choices 2089:2100 food choices 2089:2100 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 7 14 theme adequate 1504:1511 arg1 sleepers 1513:1520 adequate sleepers 1504:1520 adequate sleepers with no social jetlag 1504:1542 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 9 15 theme present 1716:1722 arg1 study 1724:1728 The present study 1712:1728 The present study 1712:1728 CONCLUSIONS The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. 35039109 7 16 with sleepers 1387:1394 arg1 jetlag 1408:1413 social jetlag 1401:1413 social jetlag 1401:1413 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 9 17 theme adiposity 1876:1884 arg1 markers 1865:1871 markers 1865:1871 markers of adiposity 1865:1884 CONCLUSIONS The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. 35039109 6 18 theme 0·8 1162:1164 arg1 energy 1168:1173 0·8 % energy 1162:1173 0·8 % energy 1162:1173 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 18 theme 0·8 1162:1164 arg1 carbohydrate 1148:1159 total carbohydrate 1142:1159 total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) 1142:1193 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 7 19 theme adequate 1378:1385 arg1 sleepers 1387:1394 adequate sleepers 1378:1394 adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) 1378:1473 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 6 20 theme % 1112:1112 arg1 energy 1114:1119 0·9 % energy 1108:1119 0·9 % energy 1108:1119 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 20 theme % 1112:1112 arg1 sugars 1093:1098 non-milk extrinsic sugars 1074:1098 non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4) 1074:1139 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 1 21 theme social 375:380 arg1 status 389:394 social jetlag status 375:394 social jetlag status 375:394 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 6 22 theme non-starch 1207:1216 arg1 polysaccharides 1218:1232 non-starch polysaccharides 1207:1232 a lower non-starch polysaccharides fibre intake 1199:1245 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 0 23 theme Rolling 262:268 arg1 Programme 270:278 Rolling Programme 262:278 Rolling Programme 262:278 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 8 24 theme social 1566:1571 arg1 jetlag 1573:1578 social jetlag 1566:1578 social jetlag 1566:1578 Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk. 35039109 2 25 theme 4-d 575:577 arg1 diary 584:588 4-d food diary and self-reported sleep data 575:617 diary 584:588 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 5 26 contain had 858:860 arg1 % 856:856 14 % 853:856 14 % 853:856 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 5 26 contain had 858:860 arg2 difference 868:877 > 2 h difference 862:877 > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag) 862:957 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 8 27 theme risk 1694:1697 arg1 markers 1659:1665 other markers 1653:1665 other markers of cardiometabolic disease risk 1653:1697 Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk. 35039109 7 28 theme fibre 1357:1361 arg1 intakes 1363:1369 fibre intakes 1357:1369 fibre intakes 1357:1369 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 10 29 from intakes 1933:1939 arg1 individuals 1949:1959 individuals 1949:1959 individuals with adequate weekly sleep duration 1949:1995 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 0 30 theme fibre 138:142 arg1 intakes 144:150 lower fibre intakes 132:150 lower fibre intakes in those with adequate sleep duration 132:188 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 1 31 theme nutrient 401:408 arg1 intake 410:415 nutrient intake 401:415 nutrient intake 401:415 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 7 32 theme jetlag 1467:1472 arg1 sleepers 1387:1394 adequate sleepers 1378:1394 adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) 1378:1473 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 7 32 theme jetlag 1467:1472 arg1 sleepers 1436:1443 all short sleepers 1426:1443 adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) 1378:1473 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 10 33 theme food 2089:2092 arg1 choices 2094:2100 food choices 2089:2100 food choices 2089:2100 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 7 34 with sleepers 1436:1443 arg1 jetlag 1408:1413 social jetlag 1401:1413 social jetlag 1401:1413 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 6 35 theme sugars 1093:1098 arg1 intakes 1063:1069 higher intakes 1056:1069 higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake 1056:1245 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 5 36 dep difference 868:877 arg1 h 866:866 h 866:866 h 866:866 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 1 37 from intake 410:415 arg1 population 526:535 a nationally representative UK adult population 489:535 a nationally representative UK adult population 489:535 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 10 38 theme habits 2079:2084 arg1 impact 2053:2058 the adverse impact 2041:2058 the adverse impact of irregular sleep habits on food choices 2041:2100 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 8 39 theme other 1653:1657 arg1 markers 1659:1665 other markers 1653:1665 other markers of cardiometabolic disease risk 1653:1697 Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk. 35039109 0 40 from Diet 236:239 arg1 analysis 209:216 a cross-sectional analysis 191:216 a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9) 191:290 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 8 41 theme disease 1686:1692 arg1 risk 1694:1697 cardiometabolic disease risk 1670:1697 cardiometabolic disease risk 1670:1697 Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk. 35039109 6 42 dep energy 1168:1173 arg1 % 1179:1179 95 % CI: 0·2, 1·4 1176:1192 % 1179:1179 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 10 43 theme adequate 1966:1973 arg1 duration 1988:1995 adequate weekly sleep duration 1966:1995 adequate weekly sleep duration 1966:1995 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 7 44 theme short 1323:1327 arg1 sleep 1329:1333 short sleep 1323:1333 short sleep 1323:1333 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 10 45 theme fibre 1927:1931 arg1 intakes 1933:1939 lower fibre intakes 1921:1939 lower fibre intakes even in individuals with adequate weekly sleep duration 1921:1995 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 0 46 theme extrinsic 77:85 arg1 sugars 87:92 non-milk extrinsic sugars 68:92 non-milk extrinsic sugars 68:92 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 5 47 theme sleep 890:894 arg1 duration 896:903 average sleep duration 882:903 average sleep duration 882:903 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 7 48 theme short 1430:1434 arg1 sleepers 1436:1443 all short sleepers 1426:1443 adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) 1378:1473 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 2 49 theme UK 628:629 arg1 Diet 640:643 the UK National Diet 624:643 the UK National Diet 624:643 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 10 50 theme lower 1921:1925 arg1 intakes 1933:1939 lower fibre intakes 1921:1939 lower fibre intakes even in individuals with adequate weekly sleep duration 1921:1995 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 10 51 with individuals 1949:1959 arg1 duration 1988:1995 adequate weekly sleep duration 1966:1995 adequate weekly sleep duration 1966:1995 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 6 52 theme sleep 996:1000 arg1 h 1020:1020 ≥ 7-< 9 h 1012:1020 ≥ 7-< 9 h 1012:1020 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 52 theme sleep 996:1000 arg1 duration 1002:1009 those reporting optimal sleep duration 972:1009 those reporting optimal sleep duration (≥ 7-< 9 h) 972:1021 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 2 53 theme Rolling 666:672 arg1 Programme 674:682 Rolling Programme 2008-2017 666:692 Rolling Programme 2008-2017 666:692 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 0 54 theme Short 0:4 arg1 sleep 6:10 Short sleep 0:10 Short sleep 0:10 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 0 55 theme Nutrition 245:253 arg1 Survey 255:260 Nutrition Survey 245:260 Nutrition Survey 245:260 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 6 56 theme reporting 978:986 arg1 h 1020:1020 ≥ 7-< 9 h 1012:1020 ≥ 7-< 9 h 1012:1020 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 56 theme reporting 978:986 arg1 duration 1002:1009 those reporting optimal sleep duration 972:1009 those reporting optimal sleep duration (≥ 7-< 9 h) 972:1021 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 2 57 theme Nutrition 649:657 arg1 Survey 659:664 Nutrition Survey 649:664 Nutrition Survey 649:664 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 6 58 theme lower 1201:1205 arg1 intake 1240:1245 a lower non-starch polysaccharides fibre intake 1199:1245 a lower non-starch polysaccharides fibre intake 1199:1245 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 58 theme lower 1201:1205 arg1 sugars 1093:1098 non-milk extrinsic sugars 1074:1098 non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4) 1074:1139 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 7 59 theme social 1401:1406 arg1 jetlag 1408:1413 social jetlag 1401:1413 social jetlag 1401:1413 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 5 60 theme social 944:949 arg1 nights 936:941 weekend nights 928:941 weekend nights (social jetlag) 928:957 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 5 60 theme social 944:949 arg1 jetlag 951:956 social jetlag 944:956 social jetlag 944:956 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 1 61 from factors 478:484 arg1 population 526:535 a nationally representative UK adult population 489:535 a nationally representative UK adult population 489:535 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 10 62 theme Social 1887:1892 arg1 jetlag 1894:1899 Social jetlag 1887:1899 Social jetlag 1887:1899 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 0 63 theme higher 50:55 arg1 intakes 57:63 higher intakes 50:63 higher intakes of non-milk extrinsic sugars 50:92 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 6 64 dep g/d 1253:1255 arg1 -0·2 1272:1275 -0·2 1272:1275 -0·2 1272:1275 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 0 65 dep associated 34:43 arg1 analysis 209:216 a cross-sectional analysis 191:216 a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9) 191:290 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 6 66 theme % 1261:1261 arg1 g/d 1253:1255 -0·5 g/d 1248:1255 -0·5 g/d 1248:1255 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 66 theme % 1261:1261 arg1 CI 1263:1264 95 % CI -0·8 1258:1269 95 % CI -0·8 1258:1269 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 10 67 theme irregular 2063:2071 arg1 habits 2079:2084 irregular sleep habits 2063:2084 irregular sleep habits 2063:2084 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 1 68 from composition 440:450 arg1 population 526:535 a nationally representative UK adult population 489:535 a nationally representative UK adult population 489:535 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 9 69 theme NMES 1816:1819 arg1 intakes 1805:1811 higher intakes 1798:1811 higher intakes of NMES 1798:1819 CONCLUSIONS The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. 35039109 1 70 theme representative 502:515 arg1 population 526:535 a nationally representative UK adult population 489:535 a nationally representative UK adult population 489:535 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 0 71 dep Diet 236:239 arg1 Programme 270:278 Rolling Programme 262:278 Rolling Programme 262:278 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 6 72 dep energy 1114:1119 arg1 % 1125:1125 95 % CI: 0·4, 1·4 1122:1138 % 1125:1125 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 73 theme 7-< 1014:1016 arg1 h 1020:1020 ≥ 7-< 9 h 1012:1020 ≥ 7-< 9 h 1012:1020 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 73 theme 7-< 1014:1016 arg1 duration 1002:1009 those reporting optimal sleep duration 972:1009 those reporting optimal sleep duration (≥ 7-< 9 h) 972:1021 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 3 74 theme UK 703:704 arg1 population 718:727 UK free-living population 703:727 UK free-living population 703:727 SETTING UK free-living population. 35039109 1 75 theme adult 520:524 arg1 population 526:535 a nationally representative UK adult population 489:535 a nationally representative UK adult population 489:535 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 9 76 theme social 1764:1769 arg1 jetlag 1771:1776 social jetlag 1764:1776 social jetlag 1764:1776 CONCLUSIONS The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. 35039109 10 77 theme sleep 1982:1986 arg1 duration 1988:1995 adequate weekly sleep duration 1966:1995 adequate weekly sleep duration 1966:1995 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 9 78 theme sleep 1831:1835 arg1 duration 1837:1844 only sleep duration 1826:1844 only sleep duration 1826:1844 CONCLUSIONS The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. 35039109 0 79 theme adequate 166:173 arg1 duration 181:188 adequate sleep duration 166:188 adequate sleep duration 166:188 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 1 80 theme nutrient 418:425 arg1 status 427:432 nutrient status 418:432 nutrient status 418:432 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 6 81 theme polysaccharides 1218:1232 arg1 intake 1240:1245 a lower non-starch polysaccharides fibre intake 1199:1245 a lower non-starch polysaccharides fibre intake 1199:1245 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 81 theme polysaccharides 1218:1232 arg1 sugars 1093:1098 non-milk extrinsic sugars 1074:1098 non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4) 1074:1139 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 2 82 theme food 579:582 arg1 diary 584:588 4-d food diary and self-reported sleep data 575:617 diary 584:588 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 8 83 from differences 1638:1648 arg1 markers 1659:1665 other markers 1653:1665 other markers of cardiometabolic disease risk 1653:1697 Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk. 35039109 8 84 theme greater 1601:1607 arg1 adiposity 1609:1617 greater adiposity 1601:1617 greater adiposity 1601:1617 Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk. 35039109 7 85 theme social 1460:1465 arg1 jetlag 1467:1472 social jetlag 1460:1472 social jetlag 1460:1472 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 2 86 dep DESIGN 538:543 arg1 study 563:567 A cross-sectional study 545:567 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 538:693 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 10 87 theme catch-up 2009:2016 arg1 sleep 2018:2022 catch-up sleep 2009:2022 catch-up sleep 2009:2022 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 6 88 theme higher 1056:1061 arg1 intakes 1063:1069 higher intakes 1056:1069 higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake 1056:1245 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 10 89 theme sleep 2073:2077 arg1 habits 2079:2084 irregular sleep habits 2063:2084 irregular sleep habits 2063:2084 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 2 90 theme sleep 608:612 arg1 data 614:617 4-d food diary and self-reported sleep data 575:617 data 614:617 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 7 91 theme fibre 1485:1489 arg1 intakes 1491:1497 lower fibre intakes 1479:1497 lower fibre intakes 1479:1497 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 6 92 dep associated 1040:1049 arg1 g/d 1253:1255 -0·5 g/d 1248:1255 -0·5 g/d 1248:1255 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 92 dep associated 1040:1049 arg1 CI 1263:1264 95 % CI -0·8 1258:1269 95 % CI -0·8 1258:1269 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 93 theme % 1166:1166 arg1 energy 1168:1173 0·8 % energy 1162:1173 0·8 % energy 1162:1173 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 93 theme % 1166:1166 arg1 carbohydrate 1148:1159 total carbohydrate 1142:1159 total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) 1142:1193 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 1 94 theme cardio-metabolic 456:471 arg1 factors 478:484 cardio-metabolic risk factors 456:484 cardio-metabolic risk factors 456:484 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 5 95 theme < 828:828 arg1 h 832:832 < 7 h 828:832 < 7 h 828:832 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 5 95 theme < 828:828 arg1 sleepers 818:825 short sleepers 812:825 short sleepers (< 7 h) 812:833 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 0 96 from Survey 255:260 arg1 analysis 209:216 a cross-sectional analysis 191:216 a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9) 191:290 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 6 97 theme 0·9 1108:1110 arg1 energy 1114:1119 0·9 % energy 1108:1119 0·9 % energy 1108:1119 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 97 theme 0·9 1108:1110 arg1 sugars 1093:1098 non-milk extrinsic sugars 1074:1098 non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4) 1074:1139 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 0 98 theme lower 132:136 arg1 intakes 144:150 lower fibre intakes 132:150 lower fibre intakes in those with adequate sleep duration 132:188 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 1 99 theme jetlag 382:387 arg1 status 389:394 social jetlag status 375:394 social jetlag status 375:394 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 10 100 theme adverse 2045:2051 arg1 impact 2053:2058 the adverse impact 2041:2058 the adverse impact of irregular sleep habits on food choices 2041:2100 Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices. 35039109 7 101 theme lower 1479:1483 arg1 intakes 1491:1497 lower fibre intakes 1479:1497 lower fibre intakes 1479:1497 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 7 102 theme social 1339:1344 arg1 jetlag 1346:1351 social jetlag 1339:1351 social jetlag 1339:1351 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 2 103 theme cross-sectional 547:561 arg1 study 563:567 A cross-sectional study 545:567 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 538:693 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 8 104 theme cardiometabolic 1670:1684 arg1 risk 1694:1697 cardiometabolic disease risk 1670:1697 cardiometabolic disease risk 1670:1697 Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk. 35039109 0 105 theme Years 281:285 arg1 1-9 287:289 Years 1-9 281:289 Years 1-9 281:289 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 0 105 theme Years 281:285 arg1 Diet 236:239 the National Diet 223:239 the National Diet 223:239 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 1 106 with interactions 335:346 arg1 status 427:432 nutrient status 418:432 nutrient status 418:432 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 1 106 with interactions 335:346 arg1 composition 440:450 body composition 435:450 body composition 435:450 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 1 106 with interactions 335:346 arg1 factors 478:484 cardio-metabolic risk factors 456:484 cardio-metabolic risk factors 456:484 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 1 106 with interactions 335:346 arg1 intake 410:415 nutrient intake 401:415 nutrient intake 401:415 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 6 107 theme extrinsic 1083:1091 arg1 intake 1240:1245 a lower non-starch polysaccharides fibre intake 1199:1245 a lower non-starch polysaccharides fibre intake 1199:1245 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 107 theme extrinsic 1083:1091 arg1 energy 1114:1119 0·9 % energy 1108:1119 0·9 % energy 1108:1119 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 107 theme extrinsic 1083:1091 arg1 NMES 1101:1104 NMES 1101:1104 NMES 1101:1104 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 107 theme extrinsic 1083:1091 arg1 sugars 1093:1098 non-milk extrinsic sugars 1074:1098 non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4) 1074:1139 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 107 theme extrinsic 1083:1091 arg1 carbohydrate 1148:1159 total carbohydrate 1142:1159 total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) 1142:1193 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 0 108 theme non-milk 68:75 arg1 sugars 87:92 non-milk extrinsic sugars 68:92 non-milk extrinsic sugars 68:92 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 1 109 with associations 318:329 arg1 status 427:432 nutrient status 418:432 nutrient status 418:432 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 1 109 with associations 318:329 arg1 composition 440:450 body composition 435:450 body composition 435:450 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 1 109 with associations 318:329 arg1 factors 478:484 cardio-metabolic risk factors 456:484 cardio-metabolic risk factors 456:484 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 1 109 with associations 318:329 arg1 intake 410:415 nutrient intake 401:415 nutrient intake 401:415 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 0 110 theme social 99:104 arg1 jetlag 106:111 social jetlag 99:111 social jetlag 99:111 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 7 111 dep jetlag 1467:1472 arg1 regardless 1446:1455 regardless 1446:1455 regardless 1446:1455 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 5 112 dep h 866:866 arg1 2 864:864 2 864:864 2 864:864 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 0 113 theme sugars 87:92 arg1 intakes 57:63 higher intakes 50:63 higher intakes of non-milk extrinsic sugars 50:92 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 0 114 theme cross-sectional 193:207 arg1 analysis 209:216 a cross-sectional analysis 191:216 a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9) 191:290 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 5 115 theme average 882:888 arg1 duration 896:903 average sleep duration 882:903 average sleep duration 882:903 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 2 116 dep Diet 640:643 arg1 Programme 674:682 Rolling Programme 2008-2017 666:692 Rolling Programme 2008-2017 666:692 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 7 117 theme significant 1291:1301 arg1 interaction 1303:1313 a significant interaction 1289:1313 a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag 1289:1542 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 2 118 theme National 631:638 arg1 Diet 640:643 the UK National Diet 624:643 the UK National Diet 624:643 DESIGN A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. 35039109 4 119 theme aged 760:763 arg1 adults 753:758 5015 adults 748:758 5015 adults aged 19-64 years 748:775 SUBJECTS Totally, 5015 adults aged 19-64 years. 35039109 8 120 theme Short 1545:1549 arg1 sleep 1551:1555 Short sleep 1545:1555 Short sleep 1545:1555 Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk. 35039109 9 121 theme short 1748:1752 arg1 sleep 1754:1758 short sleep 1748:1758 short sleep 1748:1758 CONCLUSIONS The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. 35039109 6 122 theme fibre 1234:1238 arg1 intake 1240:1245 a lower non-starch polysaccharides fibre intake 1199:1245 a lower non-starch polysaccharides fibre intake 1199:1245 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 122 theme fibre 1234:1238 arg1 sugars 1093:1098 non-milk extrinsic sugars 1074:1098 non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4) 1074:1139 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 1 123 theme sleep 356:360 arg1 duration 362:369 sleep duration 356:369 sleep duration 356:369 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 0 124 theme National 227:234 arg1 Diet 236:239 the National Diet 223:239 the National Diet 223:239 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 0 124 theme National 227:234 arg1 1-9 287:289 Years 1-9 281:289 Years 1-9 281:289 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 6 125 theme optimal 988:994 arg1 h 1020:1020 ≥ 7-< 9 h 1012:1020 ≥ 7-< 9 h 1012:1020 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 6 125 theme optimal 988:994 arg1 duration 1002:1009 those reporting optimal sleep duration 972:1009 those reporting optimal sleep duration (≥ 7-< 9 h) 972:1021 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 0 126 theme social 16:21 arg1 jetlag 23:28 social jetlag 16:28 social jetlag 16:28 Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9). 35039109 9 127 dep CONCLUSIONS 1700:1710 arg1 reports 1730:1736 reports 1730:1736 reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity 1730:1884 CONCLUSIONS The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. 35039109 7 128 with sleepers 1513:1520 arg1 jetlag 1537:1542 no social jetlag 1527:1542 no social jetlag 1527:1542 There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. 35039109 1 129 theme risk 473:476 arg1 factors 478:484 cardio-metabolic risk factors 456:484 cardio-metabolic risk factors 456:484 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 6 130 theme short 1024:1028 arg1 sleep 1030:1034 short sleep 1024:1034 short sleep 1024:1034 Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). 35039109 9 131 theme higher 1798:1803 arg1 intakes 1805:1811 higher intakes 1798:1811 higher intakes of NMES 1798:1819 CONCLUSIONS The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. 35039109 5 132 from difference 868:877 arg1 duration 896:903 average sleep duration 882:903 average sleep duration 882:903 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 5 133 theme weekend 928:934 arg1 nights 936:941 weekend nights 928:941 weekend nights (social jetlag) 928:957 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 5 133 theme weekend 928:934 arg1 jetlag 951:956 social jetlag 944:956 social jetlag 944:956 RESULTS Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). 35039109 1 134 from status 427:432 arg1 population 526:535 a nationally representative UK adult population 489:535 a nationally representative UK adult population 489:535 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35039109 1 135 theme UK 517:518 arg1 population 526:535 a nationally representative UK adult population 489:535 a nationally representative UK adult population 489:535 OBJECTIVE To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. 35807856 4 0 theme HFD 787:789 arg1 conversion 773:782 conversion 773:782 conversion of HFD to LFD 773:796 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 11 1 theme gut 2328:2330 arg1 regulation 2310:2319 the beneficial regulation 2295:2319 the beneficial regulation of the gut microbiota and metabolites 2295:2357 The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites. 35807856 4 2 theme +12 877:879 arg1 % 880:880 % 880:880 % 880:880 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 6 3 theme microbiota 1286:1295 arg1 homeostasis 1297:1307 intestinal microbiota homeostasis 1275:1307 intestinal microbiota homeostasis 1275:1307 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 7 4 theme epididymal 1480:1489 arg1 area 1501:1504 epididymal adipocyte area 1480:1504 epididymal adipocyte area 1480:1504 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 4 5 theme gut 626:628 arg1 composition 641:651 gut microbiota composition 626:651 gut microbiota composition 626:651 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 6 6 theme % 1156:1156 arg1 FF 1158:1159 12% FF 1154:1159 12% FF 1154:1159 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 1 7 theme dietary 163:169 arg1 fibers 171:176 dietary fibers 163:176 dietary fibers (DF) 163:181 Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. 35807856 1 7 theme dietary 163:169 arg1 DF 179:180 DF 179:180 DF 179:180 Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. 35807856 7 8 theme SCFAs 1635:1639 arg1 level 1609:1613 the level 1605:1613 the level of inflammation and SCFAs 1605:1639 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 8 9 from intestine 1789:1797 arg1 abundance 1713:1721 the abundance 1709:1721 the abundance 1709:1721 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 3 10 from effect 464:469 arg1 obesity 480:486 obesity 480:486 obesity 480:486 This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. 35807856 7 11 theme inflammation 1618:1629 arg1 level 1609:1613 the level 1605:1613 the level of inflammation and SCFAs 1605:1639 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 4 12 theme FF 813:814 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 12 theme FF 813:814 arg1 group 816:820 high-fat +8% FF group 800:820 high-fat +8% FF group (8% FF) 800:828 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 12 theme FF 813:814 arg1 % 824:824 8% FF 823:827 8% FF 823:827 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 8 13 from Bifidobacterium 1730:1744 arg1 intestine 1789:1797 the intestine 1785:1797 the intestine 1785:1797 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 4 14 theme biochemical 598:608 arg1 parameters 610:619 Physiological, histological, and biochemical parameters 565:619 Physiological, histological, and biochemical parameters 565:619 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 1 15 theme metabolic 93:101 arg1 syndrome 103:110 metabolic syndrome 93:110 metabolic syndrome 93:110 Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. 35807856 3 16 theme obesity 523:529 arg1 prevention 509:518 its prevention 505:518 its prevention of obesity by modulating the gut microbiota 505:562 This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. 35807856 11 17 theme 12 2244:2245 arg1 % 2246:2246 % 2246:2246 % 2246:2246 The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites. 35807856 9 18 with treatment 1888:1896 arg1 antibiotics 1903:1913 antibiotics 1903:1913 antibiotics (12% FF + AB) 1903:1927 Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. 35807856 8 19 theme negative 1812:1819 arg1 correlation 1821:1831 a negative correlation 1810:1831 a negative correlation with obesity and insulin resistance 1810:1867 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 4 20 theme % 907:907 arg1 FF 909:910 12% FF 905:910 12% FF 905:910 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 6 21 theme 12 1154:1155 arg1 % 1156:1156 % 1156:1156 % 1156:1156 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 6 22 theme short-chain 1342:1352 arg1 SCFAs 1367:1371 SCFAs 1367:1371 SCFAs 1367:1371 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 6 22 theme short-chain 1342:1352 arg1 acids 1360:1364 short-chain fatty acids 1342:1364 short-chain fatty acids (SCFAs) (p < 0.05) 1342:1383 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 6 22 theme short-chain 1342:1352 arg1 < 1377:1377 p < 0.05 1375:1382 p < 0.05 1375:1382 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 7 23 with Consistent 1386:1395 arg1 results 1406:1412 the results 1402:1412 the results of 12% FF 1402:1422 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 3 24 theme gut 549:551 arg1 microbiota 553:562 the gut microbiota 545:562 the gut microbiota 545:562 This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. 35807856 9 25 dep antibiotics 1903:1913 arg1 % 1918:1918 12% 1916:1918 12% FF + AB 1916:1926 Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. 35807856 5 26 from tissue 1106:1111 arg1 production 1076:1085 heat production 1071:1085 heat production from brown adipose tissue (BAT) (p < 0.05) 1071:1128 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 1 27 theme global 129:134 arg1 problem 150:156 a global public health problem 127:156 a global public health problem 127:156 Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. 35807856 4 28 theme high-fat 831:838 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 28 theme high-fat 831:838 arg1 group 848:852 high-fat +12% FF group 831:852 high-fat +12% FF group (12% FF) 831:861 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 28 theme high-fat 831:838 arg1 % 857:857 12% FF 855:860 12% FF 855:860 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 7 29 dep weight 1469:1474 arg1 the 1460:1462 the 1460:1462 the 1460:1462 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 10 30 theme acid 2113:2116 arg1 pathway 2128:2134 the cyanogenic amino acid metabolic pathway 2092:2134 the cyanogenic amino acid metabolic pathway 2092:2134 The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. 35807856 1 31 theme health 143:148 arg1 problem 150:156 a global public health problem 127:156 a global public health problem 127:156 Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. 35807856 7 32 theme FF 1421:1422 arg1 results 1406:1412 the results 1402:1412 the results of 12% FF 1402:1422 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 4 33 theme % 843:843 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 33 theme % 843:843 arg1 group 848:852 high-fat +12% FF group 831:852 high-fat +12% FF group (12% FF) 831:861 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 33 theme % 843:843 arg1 % 857:857 12% FF 855:860 12% FF 855:860 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 10 34 theme cyanogenic 2096:2105 arg1 pathway 2128:2134 the cyanogenic amino acid metabolic pathway 2092:2134 the cyanogenic amino acid metabolic pathway 2092:2134 The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. 35807856 7 35 theme 12 1417:1418 arg1 % 1419:1419 % 1419:1419 % 1419:1419 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 4 36 dep LFD 768:770 arg1 conversion 773:782 conversion 773:782 conversion of HFD to LFD 773:796 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 37 theme diet 730:733 arg1 HFD 742:744 HFD 742:744 HFD 742:744 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 37 theme diet 730:733 arg1 group 735:739 high-fat diet group 721:739 high-fat diet group (HFD) 721:745 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 37 theme diet 730:733 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 5 38 theme adipose 1098:1104 arg1 BAT 1114:1116 BAT 1114:1116 BAT 1114:1116 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 5 38 theme adipose 1098:1104 arg1 tissue 1106:1111 brown adipose tissue 1092:1111 brown adipose tissue (BAT) (p < 0.05) 1092:1128 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 5 38 theme adipose 1098:1104 arg1 < 1122:1122 p < 0.05 1120:1127 p < 0.05 1120:1127 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 2 39 theme water-binding 365:377 arg1 capacity 379:386 water-binding capacity 365:386 water-binding capacity 365:386 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 8 40 theme % 1655:1655 arg1 supplementation 1660:1674 12% FF supplementation 1653:1674 12% FF supplementation 1653:1674 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 8 40 theme % 1655:1655 arg1 Meanwhile 1642:1650 Meanwhile 1642:1650 Meanwhile 1642:1650 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 4 41 dep group 898:902 arg1 AB 914:915 AB 914:915 AB 914:915 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 41 dep group 898:902 arg1 FF 909:910 12% FF 905:910 12% FF 905:910 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 42 theme FF 859:860 arg1 group 848:852 high-fat +12% FF group 831:852 high-fat +12% FF group (12% FF) 831:861 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 42 theme FF 859:860 arg1 % 857:857 12% FF 855:860 12% FF 855:860 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 2 43 theme viscosity 354:362 arg1 mixture 321:327 a synthetic mixture 309:327 a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability 309:425 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 0 44 theme Functional 0:9 arg1 Fiber 11:15 Functional Fiber 0:15 Functional Fiber 0:15 Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota. 35807856 5 45 theme 12 949:950 arg1 % 951:951 % 951:951 % 951:951 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 7 46 theme significant 1568:1578 arg1 difference 1580:1589 no significant difference 1565:1589 no significant difference (p > 0.05) in the level of inflammation and SCFAs 1565:1639 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 7 46 theme significant 1568:1578 arg1 > 1594:1594 p > 0.05 1592:1599 p > 0.05 1592:1599 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 6 47 theme acids 1360:1364 arg1 production 1328:1337 the production 1324:1337 the production of short-chain fatty acids (SCFAs) (p < 0.05) 1324:1383 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 4 48 dep groups 692:697 arg1 HFD 742:744 HFD 742:744 HFD 742:744 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 group 816:820 high-fat +8% FF group 800:820 high-fat +8% FF group (8% FF) 800:828 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 % 824:824 8% FF 823:827 8% FF 823:827 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 % 857:857 12% FF 855:860 12% FF 855:860 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 group 708:712 control group 700:712 control group (Con) 700:718 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 FF 882:883 high-fat +12% FF 868:883 high-fat +12% FF 868:883 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 group 761:765 low-fat diet group 748:765 low-fat diet group (LFD, conversion of HFD to LFD) 748:797 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 group 735:739 high-fat diet group 721:739 high-fat diet group (HFD) 721:745 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 Con 715:717 Con 715:717 Con 715:717 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 group 848:852 high-fat +12% FF group 831:852 high-fat +12% FF group (12% FF) 831:861 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 48 dep groups 692:697 arg1 group 898:902 antibiotic group 887:902 antibiotic group (12% FF + AB) 887:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 8 49 theme p 1696:1696 arg1 increase 1686:1693 an increase 1683:1693 an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance 1683:1867 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 8 49 theme p 1696:1696 arg1 < 1698:1698 p < 0.05 1696:1703 p < 0.05 1696:1703 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 8 50 from abundance 1713:1721 arg1 intestine 1789:1797 the intestine 1785:1797 the intestine 1785:1797 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 10 51 theme serum 2153:2157 arg1 concentration 2169:2181 the serum succinate concentration 2149:2181 the serum succinate concentration relative to the HFD group 2149:2207 The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. 35807856 5 52 theme heat 1071:1074 arg1 production 1076:1085 heat production 1071:1085 heat production from brown adipose tissue (BAT) (p < 0.05) 1071:1128 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 2 53 theme capacity 398:405 arg1 mixture 321:327 a synthetic mixture 309:327 a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability 309:425 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 8 54 theme 12 1653:1654 arg1 % 1655:1655 % 1655:1655 % 1655:1655 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 4 55 theme low-fat 748:754 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 55 theme low-fat 748:754 arg1 group 761:765 low-fat diet group 748:765 low-fat diet group (LFD, conversion of HFD to LFD) 748:797 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 8 56 theme FF 1657:1658 arg1 supplementation 1660:1674 12% FF supplementation 1653:1674 12% FF supplementation 1653:1674 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 8 56 theme FF 1657:1658 arg1 Meanwhile 1642:1650 Meanwhile 1642:1650 Meanwhile 1642:1650 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 11 57 theme overall 2214:2220 arg1 results 2222:2228 The overall results 2210:2228 The overall results 2210:2228 The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites. 35807856 2 58 theme synthetic 311:319 arg1 mixture 321:327 a synthetic mixture 309:327 a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability 309:425 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 6 59 theme morphological 1209:1221 arg1 integrity 1223:1231 the intestinal morphological integrity 1194:1231 the intestinal morphological integrity 1194:1231 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 5 60 theme body 985:988 arg1 weight 990:995 body weight 985:995 body weight 985:995 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 9 61 theme FF 1957:1958 arg1 effect 1947:1952 the effect 1943:1952 the effect of FF in the HFD 1943:1969 Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. 35807856 4 62 theme Physiological 565:577 arg1 parameters 610:619 Physiological, histological, and biochemical parameters 565:619 Physiological, histological, and biochemical parameters 565:619 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 8 63 dep Coprococcus 1764:1774 arg1 genus 1776:1780 Coprococcus genus 1764:1780 Coprococcus genus 1764:1780 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 1 64 theme metabolic 211:219 arg1 syndrome 221:228 metabolic syndrome 211:228 metabolic syndrome 211:228 Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. 35807856 7 65 theme relative 1506:1513 arg1 weight 1469:1474 body weight 1464:1474 body weight 1464:1474 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 4 66 theme high-fat 868:875 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 66 theme high-fat 868:875 arg1 FF 882:883 high-fat +12% FF 868:883 high-fat +12% FF 868:883 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 67 theme histological 580:591 arg1 parameters 610:619 Physiological, histological, and biochemical parameters 565:619 Physiological, histological, and biochemical parameters 565:619 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 5 68 theme p 1120:1120 arg1 tissue 1106:1111 brown adipose tissue 1092:1111 brown adipose tissue (BAT) (p < 0.05) 1092:1128 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 5 68 theme p 1120:1120 arg1 < 1122:1122 p < 0.05 1120:1127 p < 0.05 1120:1127 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 3 69 theme FF 474:475 arg1 effect 464:469 the effect 460:469 the effect of FF on obesity 460:486 This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. 35807856 7 70 theme adipocyte 1491:1499 arg1 area 1501:1504 epididymal adipocyte area 1480:1504 epididymal adipocyte area 1480:1504 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 4 71 theme % 880:880 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 71 theme % 880:880 arg1 FF 882:883 high-fat +12% FF 868:883 high-fat +12% FF 868:883 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 9 72 from effect 1947:1952 arg1 HFD 1967:1969 the HFD 1963:1969 the HFD 1963:1969 Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. 35807856 1 73 theme intestinal 244:253 arg1 microbiota 255:264 intestinal microbiota 244:264 intestinal microbiota 244:264 Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. 35807856 10 74 theme HFD 2199:2201 arg1 group 2203:2207 the HFD group 2195:2207 the HFD group 2195:2207 The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. 35807856 8 75 theme Coprococcus 1764:1774 arg1 abundance 1713:1721 the abundance 1709:1721 the abundance 1709:1721 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 6 76 theme intestinal 1275:1284 arg1 homeostasis 1297:1307 intestinal microbiota homeostasis 1275:1307 intestinal microbiota homeostasis 1275:1307 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 7 77 theme body 1464:1467 arg1 weight 1469:1474 body weight 1464:1474 body weight 1464:1474 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 9 78 dep % 1918:1918 arg1 FF 1920:1921 FF + AB 1920:1926 FF 1920:1921 Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. 35807856 9 78 dep % 1918:1918 arg1 AB 1925:1926 FF + AB 1920:1926 AB 1925:1926 Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. 35807856 8 79 from Lactococcus 1747:1757 arg1 intestine 1789:1797 the intestine 1785:1797 the intestine 1785:1797 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 4 80 theme 12 905:906 arg1 % 907:907 % 907:907 % 907:907 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 81 theme microbiota 630:639 arg1 composition 641:651 gut microbiota composition 626:651 gut microbiota composition 626:651 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 5 82 from reduction 972:980 arg1 weight 990:995 body weight 985:995 body weight 985:995 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 5 82 from reduction 972:980 arg1 area 1022:1025 epididymal adipocyte area 1001:1025 epididymal adipocyte area 1001:1025 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 10 83 theme relative 2183:2190 arg1 concentration 2169:2181 the serum succinate concentration 2149:2181 the serum succinate concentration relative to the HFD group 2149:2207 The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. 35807856 6 84 theme systemic 1244:1251 arg1 inflammation 1253:1264 systemic inflammation 1244:1264 systemic inflammation 1244:1264 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 4 85 dep group 761:765 arg1 LFD 768:770 LFD 768:770 LFD 768:770 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 7 86 from difference 1580:1589 arg1 level 1609:1613 the level 1605:1613 the level of inflammation and SCFAs 1605:1639 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 4 87 theme % 811:811 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 87 theme % 811:811 arg1 group 816:820 high-fat +8% FF group 800:820 high-fat +8% FF group (8% FF) 800:828 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 87 theme % 811:811 arg1 % 824:824 8% FF 823:827 8% FF 823:827 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 10 88 theme 12 2057:2058 arg1 % 2059:2059 % 2059:2059 % 2059:2059 The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. 35807856 10 89 theme succinate 2159:2167 arg1 concentration 2169:2181 the serum succinate concentration 2149:2181 the serum succinate concentration relative to the HFD group 2149:2207 The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. 35807856 11 90 contain has 2251:2253 arg1 FF 2248:2249 12% FF 2244:2249 12% FF 2244:2249 The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites. 35807856 11 90 contain has 2251:2253 arg2 potential 2259:2267 the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites 2255:2357 the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites 2255:2357 The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites. 35807856 4 91 theme following 678:686 arg1 group 816:820 high-fat +8% FF group 800:820 high-fat +8% FF group (8% FF) 800:828 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 91 theme following 678:686 arg1 group 708:712 control group 700:712 control group (Con) 700:718 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 91 theme following 678:686 arg1 FF 882:883 high-fat +12% FF 868:883 high-fat +12% FF 868:883 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 91 theme following 678:686 arg1 group 761:765 low-fat diet group 748:765 low-fat diet group (LFD, conversion of HFD to LFD) 748:797 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 91 theme following 678:686 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 91 theme following 678:686 arg1 group 735:739 high-fat diet group 721:739 high-fat diet group (HFD) 721:745 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 91 theme following 678:686 arg1 group 848:852 high-fat +12% FF group 831:852 high-fat +12% FF group (12% FF) 831:861 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 5 92 theme insulin 1036:1042 arg1 sensitivity 1044:1054 insulin sensitivity 1036:1054 insulin sensitivity 1036:1054 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 8 93 dep Bifidobacterium 1730:1744 arg1 the 1726:1728 the 1726:1728 the 1726:1728 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 8 94 from increase 1686:1693 arg1 abundance 1713:1721 the abundance 1709:1721 the abundance 1709:1721 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 4 95 theme high-fat 800:807 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 95 theme high-fat 800:807 arg1 group 816:820 high-fat +8% FF group 800:820 high-fat +8% FF group (8% FF) 800:828 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 95 theme high-fat 800:807 arg1 % 824:824 8% FF 823:827 8% FF 823:827 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 7 96 theme % 1419:1419 arg1 FF 1421:1422 12% FF 1417:1422 12% FF 1417:1422 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 10 97 theme % 2059:2059 arg1 FF 2061:2062 12% FF 2057:2062 12% FF 2057:2062 The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. 35807856 1 98 theme public 136:141 arg1 problem 150:156 a global public health problem 127:156 a global public health problem 127:156 Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. 35807856 8 99 theme insulin 1850:1856 arg1 resistance 1858:1867 insulin resistance 1850:1867 insulin resistance 1850:1867 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 10 100 theme amino 2107:2111 arg1 pathway 2128:2134 the cyanogenic amino acid metabolic pathway 2092:2134 the cyanogenic amino acid metabolic pathway 2092:2134 The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. 35807856 5 101 theme adipocyte 1012:1020 arg1 area 1022:1025 epididymal adipocyte area 1001:1025 epididymal adipocyte area 1001:1025 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 8 102 with correlation 1821:1831 arg1 obesity 1838:1844 obesity 1838:1844 obesity 1838:1844 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 8 102 with correlation 1821:1831 arg1 resistance 1858:1867 insulin resistance 1850:1867 insulin resistance 1850:1867 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 7 103 theme p 1592:1592 arg1 difference 1580:1589 no significant difference 1565:1589 no significant difference (p > 0.05) in the level of inflammation and SCFAs 1565:1639 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 7 103 theme p 1592:1592 arg1 > 1594:1594 p > 0.05 1592:1599 p > 0.05 1592:1599 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 6 104 theme p 1375:1375 arg1 acids 1360:1364 short-chain fatty acids 1342:1364 short-chain fatty acids (SCFAs) (p < 0.05) 1342:1383 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 6 104 theme p 1375:1375 arg1 < 1377:1377 p < 0.05 1375:1382 p < 0.05 1375:1382 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 2 105 theme functional 282:291 arg1 fiber 293:297 a functional fiber 280:297 a functional fiber (FF) 280:302 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 2 105 theme functional 282:291 arg1 FF 300:301 FF 300:301 FF 300:301 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 5 106 theme brown 1092:1096 arg1 BAT 1114:1116 BAT 1114:1116 BAT 1114:1116 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 5 106 theme brown 1092:1096 arg1 tissue 1106:1111 brown adipose tissue 1092:1111 brown adipose tissue (BAT) (p < 0.05) 1092:1128 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 5 106 theme brown 1092:1096 arg1 < 1122:1122 p < 0.05 1120:1127 p < 0.05 1120:1127 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 11 107 theme % 2246:2246 arg1 FF 2248:2249 12% FF 2244:2249 12% FF 2244:2249 The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites. 35807856 4 108 theme FF 826:827 arg1 group 816:820 high-fat +8% FF group 800:820 high-fat +8% FF group (8% FF) 800:828 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 108 theme FF 826:827 arg1 % 824:824 8% FF 823:827 8% FF 823:827 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 109 theme high-fat 721:728 arg1 HFD 742:744 HFD 742:744 HFD 742:744 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 109 theme high-fat 721:728 arg1 group 735:739 high-fat diet group 721:739 high-fat diet group (HFD) 721:745 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 109 theme high-fat 721:728 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 11 110 dep gut 2328:2330 arg1 metabolites 2347:2357 metabolites 2347:2357 metabolites 2347:2357 The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites. 35807856 11 110 dep gut 2328:2330 arg1 microbiota 2332:2341 microbiota 2332:2341 microbiota 2332:2341 The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites. 35807856 2 111 theme fermentability 412:425 arg1 mixture 321:327 a synthetic mixture 309:327 a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability 309:425 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 4 112 theme control 700:706 arg1 Con 715:717 Con 715:717 Con 715:717 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 112 theme control 700:706 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 112 theme control 700:706 arg1 group 708:712 control group 700:712 control group (Con) 700:718 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 2 113 theme high 349:352 arg1 viscosity 354:362 high viscosity 349:362 high viscosity 349:362 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 0 114 theme Mice 25:28 arg1 Obesity 30:36 Mice Obesity 25:36 Mice Obesity 25:36 Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota. 35807856 5 115 theme % 951:951 arg1 FF 953:954 12% FF 949:954 12% FF 949:954 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 35807856 6 116 theme fatty 1354:1358 arg1 SCFAs 1367:1371 SCFAs 1367:1371 SCFAs 1367:1371 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 6 116 theme fatty 1354:1358 arg1 acids 1360:1364 short-chain fatty acids 1342:1364 short-chain fatty acids (SCFAs) (p < 0.05) 1342:1383 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 6 116 theme fatty 1354:1358 arg1 < 1377:1377 p < 0.05 1375:1382 p < 0.05 1375:1382 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 2 117 theme swelling 389:396 arg1 capacity 398:405 swelling capacity 389:405 swelling capacity 389:405 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 4 118 theme FF 845:846 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 118 theme FF 845:846 arg1 group 848:852 high-fat +12% FF group 831:852 high-fat +12% FF group (12% FF) 831:861 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 118 theme FF 845:846 arg1 % 857:857 12% FF 855:860 12% FF 855:860 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 2 119 theme capacity 379:386 arg1 mixture 321:327 a synthetic mixture 309:327 a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability 309:425 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 0 120 theme Intestinal 52:61 arg1 Microbiota 63:72 Intestinal Microbiota 52:72 Intestinal Microbiota 52:72 Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota. 35807856 4 121 theme diet 756:759 arg1 groups 692:697 the following six groups 674:697 the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB) 674:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 4 121 theme diet 756:759 arg1 group 761:765 low-fat diet group 748:765 low-fat diet group (LFD, conversion of HFD to LFD) 748:797 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 7 122 theme p 1527:1527 arg1 HFD 1522:1524 the HFD 1518:1524 the HFD (p < 0.05) 1518:1535 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 7 122 theme p 1527:1527 arg1 < 1529:1529 p < 0.05 1527:1534 p < 0.05 1527:1534 Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. 35807856 8 123 theme Bifidobacterium 1730:1744 arg1 abundance 1713:1721 the abundance 1709:1721 the abundance 1709:1721 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 10 124 theme metabolic 2118:2126 arg1 pathway 2128:2134 the cyanogenic amino acid metabolic pathway 2092:2134 the cyanogenic amino acid metabolic pathway 2092:2134 The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. 35807856 6 125 theme intestinal 1198:1207 arg1 integrity 1223:1231 the intestinal morphological integrity 1194:1231 the intestinal morphological integrity 1194:1231 Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). 35807856 8 126 theme Lactococcus 1747:1757 arg1 abundance 1713:1721 the abundance 1709:1721 the abundance 1709:1721 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 4 127 theme antibiotic 887:896 arg1 group 898:902 antibiotic group 887:902 antibiotic group (12% FF + AB) 887:916 Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). 35807856 8 128 contain had 1806:1808 arg1 abundance 1713:1721 the abundance 1709:1721 the abundance 1709:1721 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 8 128 contain had 1806:1808 arg2 correlation 1821:1831 a negative correlation 1810:1831 a negative correlation with obesity and insulin resistance 1810:1867 Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. 35807856 11 129 theme beneficial 2299:2308 arg1 regulation 2310:2319 the beneficial regulation 2295:2319 the beneficial regulation of the gut microbiota and metabolites 2295:2357 The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites. 35807856 2 130 theme polysaccharides 332:346 arg1 mixture 321:327 a synthetic mixture 309:327 a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability 309:425 We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. 35807856 5 131 theme epididymal 1001:1010 arg1 area 1022:1025 epididymal adipocyte area 1001:1025 epididymal adipocyte area 1001:1025 The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). 37402642 4 0 from spectrometry 893:904 arg1 assignments 847:857 Quantitative assignments 834:857 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course 834:968 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 4 1 theme mass 888:891 arg1 NIMS 907:910 NIMS 907:910 NIMS 907:910 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 4 1 theme mass 888:891 arg1 spectrometry 893:904 nanostructure initiator mass spectrometry 864:904 nanostructure initiator mass spectrometry (NIMS) 864:911 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 2 2 theme hydrolase 350:358 arg1 family 360:365 glycoside hydrolase family 55 340:368 glycoside hydrolase family 55 340:368 Our previous study showed strong reactivity of glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. 37402642 3 3 theme kelp 691:694 arg1 hydrolysis 667:676 efficient hydrolysis 657:676 efficient hydrolysis of untreated kelp 657:694 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 4 4 theme initiator 878:886 arg1 NIMS 907:910 NIMS 907:910 NIMS 907:910 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 4 4 theme initiator 878:886 arg1 spectrometry 893:904 nanostructure initiator mass spectrometry 864:904 nanostructure initiator mass spectrometry (NIMS) 864:911 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 2 5 theme glycoside 340:348 arg1 family 360:365 glycoside hydrolase family 55 340:368 glycoside hydrolase family 55 340:368 Our previous study showed strong reactivity of glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. 37402642 2 6 theme strong 319:324 arg1 reactivity 326:335 strong reactivity 319:335 strong reactivity of glycoside hydrolase family 55 319:368 Our previous study showed strong reactivity of glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. 37402642 1 7 dep abundant 106:113 arg1 farmable 116:123 farmable 116:123 farmable 116:123 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 4 8 theme reaction 949:956 arg1 NMR 925:927 2D HSQC NMR 917:927 2D HSQC NMR 917:927 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 4 8 theme reaction 949:956 arg1 NIMS 907:910 NIMS 907:910 NIMS 907:910 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 4 8 theme reaction 949:956 arg1 spectrometry 893:904 nanostructure initiator mass spectrometry 864:904 nanostructure initiator mass spectrometry (NIMS) 864:911 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 4 8 theme reaction 949:956 arg1 analysis 933:940 analysis 933:940 analysis of the reaction time-course 933:968 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 3 9 from family 641:646 arg1 lyase 609:613 a broad specificity alginate lyase 580:613 a broad specificity alginate lyase from polysaccharide lyase family 18 580:649 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 10 theme sugars 719:724 arg1 mixture 701:707 a mixture 699:707 a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids 699:803 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 10 theme sugars 719:724 arg1 oligomers 823:831 their soluble oligomers 809:831 their soluble oligomers 809:831 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 11 with combination 502:512 arg1 lyase 609:613 a broad specificity alginate lyase 580:613 a broad specificity alginate lyase from polysaccharide lyase family 18 580:649 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 12 theme glycoside 526:534 arg1 family 546:551 a single glycoside hydrolase family 55 β-1,3-exoglucanase 517:573 a single glycoside hydrolase family 55 β-1,3-exoglucanase 517:573 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 1 13 theme deconstruction 251:264 arg1 study 236:240 study 236:240 study of their deconstruction by simple enzyme mixtures 236:290 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 4 14 theme time-course 958:968 arg1 reaction 949:956 the reaction time-course 945:968 the reaction time-course 945:968 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 1 15 contain containing 133:142 arg2 laminarin 144:152 laminarin 144:152 laminarin 144:152 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 1 15 contain containing 133:142 arg1 biomass 125:131 an abundant, farmable biomass 103:131 an abundant, farmable biomass containing laminarin and alginate as major polysaccharides 103:190 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 1 15 contain containing 133:142 arg2 polysaccharides 176:190 major polysaccharides 170:190 major polysaccharides 170:190 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 1 15 contain containing 133:142 arg2 alginate 158:165 alginate 158:165 alginate 158:165 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 1 15 contain containing 133:142 arg1 Kelp 95:98 Kelp 95:98 Kelp 95:98 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 2 16 theme purified 391:398 arg1 laminarin 400:408 purified laminarin 391:408 purified laminarin 391:408 Our previous study showed strong reactivity of glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. 37402642 3 17 theme soluble 815:821 arg1 oligomers 823:831 their soluble oligomers 809:831 their soluble oligomers 809:831 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 4 18 theme Quantitative 834:845 arg1 assignments 847:857 Quantitative assignments 834:857 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course 834:968 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 2 19 theme reactivity 439:448 arg1 question 423:430 the question 419:430 the question of its reactivity with intact kelp 419:465 Our previous study showed strong reactivity of glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. 37402642 3 20 theme simple 712:717 arg1 sugars 719:724 simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids 712:803 simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids 712:803 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 20 theme simple 712:717 arg1 gentiobiose 735:745 gentiobiose 735:745 gentiobiose 735:745 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 20 theme simple 712:717 arg1 glucose 761:767 mannitol-end glucose 748:767 mannitol-end glucose 748:767 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 20 theme simple 712:717 arg1 glucose 726:732 glucose 726:732 glucose 726:732 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 4 21 theme nanostructure 864:876 arg1 NIMS 907:910 NIMS 907:910 NIMS 907:910 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 4 21 theme nanostructure 864:876 arg1 spectrometry 893:904 nanostructure initiator mass spectrometry 864:904 nanostructure initiator mass spectrometry (NIMS) 864:911 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 0 22 theme Quantitative 0:11 arg1 analysis 13:20 Quantitative analysis 0:20 Quantitative analysis of The High Yield Hydrolysis of Kelp by Laminarinase and Alginate Lyase. 0:93 Quantitative analysis of The High Yield Hydrolysis of Kelp by Laminarinase and Alginate Lyase. 37402642 0 23 dep Laminarinase 62:73 arg1 Lyase 88:92 Lyase 88:92 Lyase 88:92 Quantitative analysis of The High Yield Hydrolysis of Kelp by Laminarinase and Alginate Lyase. 37402642 1 24 theme major 170:174 arg1 alginate 158:165 alginate 158:165 alginate 158:165 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 1 24 theme major 170:174 arg1 polysaccharides 176:190 major polysaccharides 170:190 major polysaccharides 170:190 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 1 24 theme major 170:174 arg1 laminarin 144:152 laminarin 144:152 laminarin 144:152 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 1 25 theme simple 269:274 arg1 mixtures 283:290 simple enzyme mixtures 269:290 simple enzyme mixtures 269:290 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 5 26 theme biomass 1098:1104 arg1 composition 1076:1086 the unique polysaccharide composition 1050:1086 the unique polysaccharide composition of marine biomass 1050:1104 The data suggests that binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass are sufficient to deconstruct kelp into soluble sugars for microbial fermentation. 37402642 3 27 theme hydrolase 536:544 arg1 family 546:551 a single glycoside hydrolase family 55 β-1,3-exoglucanase 517:573 a single glycoside hydrolase family 55 β-1,3-exoglucanase 517:573 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 2 28 theme previous 297:304 arg1 study 306:310 Our previous study 293:310 Our previous study 293:310 Our previous study showed strong reactivity of glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. 37402642 1 29 theme enzyme 276:281 arg1 mixtures 283:290 simple enzyme mixtures 269:290 simple enzyme mixtures 269:290 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 4 30 theme HSQC 920:923 arg1 NMR 925:927 2D HSQC NMR 917:927 2D HSQC NMR 917:927 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 4 31 from analysis 933:940 arg1 assignments 847:857 Quantitative assignments 834:857 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course 834:968 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 3 32 theme family 546:551 arg1 combination 502:512 combination 502:512 combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 502:649 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 0 33 theme Yield 34:38 arg1 Hydrolysis 40:49 The High Yield Hydrolysis 25:49 The High Yield Hydrolysis of Kelp 25:57 Quantitative analysis of The High Yield Hydrolysis of Kelp by Laminarinase and Alginate Lyase. 37402642 3 34 theme broad 582:586 arg1 lyase 609:613 a broad specificity alginate lyase 580:613 a broad specificity alginate lyase from polysaccharide lyase family 18 580:649 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 0 35 theme High 29:32 arg1 Hydrolysis 40:49 The High Yield Hydrolysis 25:49 The High Yield Hydrolysis of Kelp 25:57 Quantitative analysis of The High Yield Hydrolysis of Kelp by Laminarinase and Alginate Lyase. 37402642 3 36 theme lyase 635:639 arg1 family 641:646 polysaccharide lyase family 18 620:649 polysaccharide lyase family 18 620:649 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 37 theme specificity 588:598 arg1 lyase 609:613 a broad specificity alginate lyase 580:613 a broad specificity alginate lyase from polysaccharide lyase family 18 580:649 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 2 38 theme laminarin 400:408 arg1 hydrolysis 377:386 hydrolysis 377:386 hydrolysis of purified laminarin 377:408 Our previous study showed strong reactivity of glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. 37402642 2 39 theme intact 455:460 arg1 kelp 462:465 intact kelp 455:465 intact kelp 455:465 Our previous study showed strong reactivity of glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. 37402642 3 40 theme mannuronic 774:783 arg1 acids 799:803 mannuronic and guluronic acids 774:803 mannuronic and guluronic acids 774:803 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 41 theme mannitol-end 748:759 arg1 sugars 719:724 simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids 712:803 simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids 712:803 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 41 theme mannitol-end 748:759 arg1 glucose 761:767 mannitol-end glucose 748:767 mannitol-end glucose 748:767 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 5 42 theme enzymes 1030:1036 arg1 combinations 1014:1025 binary combinations 1007:1025 binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass 1007:1104 The data suggests that binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass are sufficient to deconstruct kelp into soluble sugars for microbial fermentation. 37402642 5 43 theme soluble 1146:1152 arg1 sugars 1154:1159 soluble sugars 1146:1159 soluble sugars for microbial fermentation 1146:1186 The data suggests that binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass are sufficient to deconstruct kelp into soluble sugars for microbial fermentation. 37402642 0 44 theme Hydrolysis 40:49 arg1 analysis 13:20 Quantitative analysis 0:20 Quantitative analysis of The High Yield Hydrolysis of Kelp by Laminarinase and Alginate Lyase. 0:93 Quantitative analysis of The High Yield Hydrolysis of Kelp by Laminarinase and Alginate Lyase. 37402642 3 45 dep sugars 719:724 arg1 acids 799:803 mannuronic and guluronic acids 774:803 mannuronic and guluronic acids 774:803 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 45 dep sugars 719:724 arg1 sugars 719:724 simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids 712:803 simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids 712:803 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 45 dep sugars 719:724 arg1 gentiobiose 735:745 gentiobiose 735:745 gentiobiose 735:745 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 45 dep sugars 719:724 arg1 glucose 761:767 mannitol-end glucose 748:767 mannitol-end glucose 748:767 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 45 dep sugars 719:724 arg1 glucose 726:732 glucose 726:732 glucose 726:732 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 2 46 with reactivity 439:448 arg1 kelp 462:465 intact kelp 455:465 intact kelp 455:465 Our previous study showed strong reactivity of glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. 37402642 4 47 from NMR 925:927 arg1 assignments 847:857 Quantitative assignments 834:857 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course 834:968 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 4 48 theme 2D 917:918 arg1 NMR 925:927 2D HSQC NMR 917:927 2D HSQC NMR 917:927 Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR and analysis of the reaction time-course are provided. 37402642 3 49 theme untreated 681:689 arg1 kelp 691:694 untreated kelp 681:694 untreated kelp 681:694 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 5 50 theme marine 1091:1096 arg1 biomass 1098:1104 marine biomass 1091:1104 marine biomass 1091:1104 The data suggests that binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass are sufficient to deconstruct kelp into soluble sugars for microbial fermentation. 37402642 1 51 theme abundant 106:113 arg1 biomass 125:131 an abundant, farmable biomass 103:131 an abundant, farmable biomass containing laminarin and alginate as major polysaccharides 103:190 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 1 51 theme abundant 106:113 arg1 Kelp 95:98 Kelp 95:98 Kelp 95:98 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 1 52 theme excellent 206:214 arg1 substrate 222:230 an excellent model substrate 203:230 an excellent model substrate for study of their deconstruction by simple enzyme mixtures 203:290 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 3 53 theme efficient 657:665 arg1 hydrolysis 667:676 efficient hydrolysis 657:676 efficient hydrolysis of untreated kelp 657:694 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 54 theme polysaccharide 620:633 arg1 family 641:646 polysaccharide lyase family 18 620:649 polysaccharide lyase family 18 620:649 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 3 55 dep family 546:551 arg1 β-1,3-exoglucanase 556:573 β-1,3-exoglucanase 556:573 a single glycoside hydrolase family 55 β-1,3-exoglucanase 517:573 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 5 56 theme unique 1054:1059 arg1 composition 1076:1086 the unique polysaccharide composition 1050:1086 the unique polysaccharide composition of marine biomass 1050:1104 The data suggests that binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass are sufficient to deconstruct kelp into soluble sugars for microbial fermentation. 37402642 1 57 theme model 216:220 arg1 substrate 222:230 an excellent model substrate 203:230 an excellent model substrate for study of their deconstruction by simple enzyme mixtures 203:290 Kelp is an abundant, farmable biomass containing laminarin and alginate as major polysaccharides, providing an excellent model substrate for study of their deconstruction by simple enzyme mixtures. 37402642 5 58 theme microbial 1165:1173 arg1 fermentation 1175:1186 microbial fermentation 1165:1186 microbial fermentation 1165:1186 The data suggests that binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass are sufficient to deconstruct kelp into soluble sugars for microbial fermentation. 37402642 5 59 theme polysaccharide 1061:1074 arg1 composition 1076:1086 the unique polysaccharide composition 1050:1086 the unique polysaccharide composition of marine biomass 1050:1104 The data suggests that binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass are sufficient to deconstruct kelp into soluble sugars for microbial fermentation. 37402642 3 60 theme alginate 600:607 arg1 lyase 609:613 a broad specificity alginate lyase 580:613 a broad specificity alginate lyase from polysaccharide lyase family 18 580:649 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 0 61 theme Kelp 54:57 arg1 Hydrolysis 40:49 The High Yield Hydrolysis 25:49 The High Yield Hydrolysis of Kelp 25:57 Quantitative analysis of The High Yield Hydrolysis of Kelp by Laminarinase and Alginate Lyase. 37402642 3 62 theme single 519:524 arg1 family 546:551 a single glycoside hydrolase family 55 β-1,3-exoglucanase 517:573 a single glycoside hydrolase family 55 β-1,3-exoglucanase 517:573 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 37402642 5 63 theme binary 1007:1012 arg1 combinations 1014:1025 binary combinations 1007:1025 binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass 1007:1104 The data suggests that binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass are sufficient to deconstruct kelp into soluble sugars for microbial fermentation. 37402642 2 64 theme family 360:365 arg1 reactivity 326:335 strong reactivity 319:335 strong reactivity of glycoside hydrolase family 55 319:368 Our previous study showed strong reactivity of glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. 37402642 3 65 theme guluronic 789:797 arg1 acids 799:803 mannuronic and guluronic acids 774:803 mannuronic and guluronic acids 774:803 In this study, we determined that combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad specificity alginate lyase from polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. 35839485 5 0 theme intramolecular 700:713 arg1 bonds 724:728 the inherent intramolecular hydrogen bonds 687:728 the inherent intramolecular hydrogen bonds between the phosphate moiety and 3OH in the sphingosine backbones 687:794 When cholesterol is inserted into the ESM monolayer, the inherent intramolecular hydrogen bonds between the phosphate moiety and 3OH in the sphingosine backbones are destroyed. 35839485 7 1 theme ESM 1019:1021 arg1 molecule 1023:1030 the ESM molecule 1015:1030 the ESM molecule 1015:1030 The OH of the cholesterol head group can bind to the -PO-2 of the ESM molecule, and the orientation of the -PO-2 in the head groups changes to be more parallel to the interface. 35839485 2 2 theme cholesterol 373:383 arg1 concentration 385:397 cholesterol concentration 373:397 cholesterol concentration 373:397 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35839485 0 3 theme Air/Water 82:90 arg1 Interface 92:100 an Air/Water Interface 79:100 an Air/Water Interface 79:100 Mechanism by Which Cholesterol Induces Sphingomyelin Conformational Changes at an Air/Water Interface. 35839485 5 4 theme hydrogen 715:722 arg1 bonds 724:728 the inherent intramolecular hydrogen bonds 687:728 the inherent intramolecular hydrogen bonds between the phosphate moiety and 3OH in the sphingosine backbones 687:794 When cholesterol is inserted into the ESM monolayer, the inherent intramolecular hydrogen bonds between the phosphate moiety and 3OH in the sphingosine backbones are destroyed. 35839485 3 5 theme conformational 557:570 arg1 changes 572:578 sphingomyelin conformational changes 543:578 sphingomyelin conformational changes 543:578 The analysis of the spectra shows that cholesterol can induce sphingomyelin conformational changes at an air/water interface. 35839485 2 6 theme natural 324:330 arg1 sphingomyelin 336:348 natural egg sphingomyelin 324:348 natural egg sphingomyelin (ESM) 324:354 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35839485 2 6 theme natural 324:330 arg1 ESM 351:353 ESM 351:353 ESM 351:353 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35839485 7 7 theme head 979:982 arg1 group 984:988 the cholesterol head group 963:988 the cholesterol head group 963:988 The OH of the cholesterol head group can bind to the -PO-2 of the ESM molecule, and the orientation of the -PO-2 in the head groups changes to be more parallel to the interface. 35839485 7 8 theme molecule 1023:1030 arg1 -PO-2 1006:1010 the -PO-2 1002:1010 the -PO-2 of the ESM molecule 1002:1030 The OH of the cholesterol head group can bind to the -PO-2 of the ESM molecule, and the orientation of the -PO-2 in the head groups changes to be more parallel to the interface. 35839485 3 9 theme sphingomyelin 543:555 arg1 changes 572:578 sphingomyelin conformational changes 543:578 sphingomyelin conformational changes 543:578 The analysis of the spectra shows that cholesterol can induce sphingomyelin conformational changes at an air/water interface. 35839485 2 10 theme different 444:452 arg1 combinations 467:478 different polarization combinations 444:478 different polarization combinations 444:478 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35839485 2 11 theme air/water 418:426 arg1 interface 428:436 an air/water interface 415:436 an air/water interface under different polarization combinations 415:478 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35839485 2 12 theme SFG 309:311 arg1 spectra 313:319 The SFG spectra 305:319 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration 305:397 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35839485 1 13 theme molecular 194:202 arg1 level 204:208 the molecular level 190:208 the molecular level 190:208 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 5 14 theme inherent 691:698 arg1 bonds 724:728 the inherent intramolecular hydrogen bonds 687:728 the inherent intramolecular hydrogen bonds between the phosphate moiety and 3OH in the sphingosine backbones 687:794 When cholesterol is inserted into the ESM monolayer, the inherent intramolecular hydrogen bonds between the phosphate moiety and 3OH in the sphingosine backbones are destroyed. 35839485 5 15 theme ESM 672:674 arg1 monolayer 676:684 the ESM monolayer 668:684 the ESM monolayer 668:684 When cholesterol is inserted into the ESM monolayer, the inherent intramolecular hydrogen bonds between the phosphate moiety and 3OH in the sphingosine backbones are destroyed. 35839485 6 16 theme sphingosine 836:846 arg1 backbones 848:856 the sphingosine backbones 832:856 the sphingosine backbones 832:856 During this process, the sphingosine backbones become more ordered, while the conformation of the N-linked long acid chain remains unaltered. 35839485 1 17 from interactions 130:141 arg1 monolayers 176:185 cholesterol and sphingomyelin monolayers 146:185 cholesterol and sphingomyelin monolayers 146:185 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 2 18 theme sphingomyelin 336:348 arg1 spectra 313:319 The SFG spectra 305:319 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration 305:397 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35839485 2 19 theme polarization 454:465 arg1 combinations 467:478 different polarization combinations 444:478 different polarization combinations 444:478 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35839485 3 20 theme spectra 501:507 arg1 analysis 485:492 The analysis 481:492 The analysis of the spectra 481:507 The analysis of the spectra shows that cholesterol can induce sphingomyelin conformational changes at an air/water interface. 35839485 6 21 theme chain 928:932 arg1 conformation 889:900 the conformation 885:900 the conformation of the N-linked long acid chain 885:932 During this process, the sphingosine backbones become more ordered, while the conformation of the N-linked long acid chain remains unaltered. 35839485 2 22 theme egg 332:334 arg1 sphingomyelin 336:348 natural egg sphingomyelin 324:348 natural egg sphingomyelin (ESM) 324:354 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35839485 2 22 theme egg 332:334 arg1 ESM 351:353 ESM 351:353 ESM 351:353 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35839485 1 23 theme broadband 229:237 arg1 spectroscopy 276:287 high-resolution broadband sum frequency generation vibrational spectroscopy 213:287 high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) 213:302 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 1 23 theme broadband 229:237 arg1 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 0 24 theme Sphingomyelin 39:51 arg1 Changes 68:74 Sphingomyelin Conformational Changes 39:74 Sphingomyelin Conformational Changes 39:74 Mechanism by Which Cholesterol Induces Sphingomyelin Conformational Changes at an Air/Water Interface. 35839485 7 25 theme head 1073:1076 arg1 groups 1078:1083 the head groups 1069:1083 the head groups 1069:1083 The OH of the cholesterol head group can bind to the -PO-2 of the ESM molecule, and the orientation of the -PO-2 in the head groups changes to be more parallel to the interface. 35839485 6 26 theme acid 923:926 arg1 chain 928:932 the N-linked long acid chain 905:932 the N-linked long acid chain 905:932 During this process, the sphingosine backbones become more ordered, while the conformation of the N-linked long acid chain remains unaltered. 35839485 1 27 theme sum 239:241 arg1 spectroscopy 276:287 high-resolution broadband sum frequency generation vibrational spectroscopy 213:287 high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) 213:302 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 1 27 theme sum 239:241 arg1 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 5 28 from bonds 724:728 arg1 backbones 786:794 the sphingosine backbones 770:794 the sphingosine backbones 770:794 When cholesterol is inserted into the ESM monolayer, the inherent intramolecular hydrogen bonds between the phosphate moiety and 3OH in the sphingosine backbones are destroyed. 35839485 5 29 theme sphingosine 774:784 arg1 backbones 786:794 the sphingosine backbones 770:794 the sphingosine backbones 770:794 When cholesterol is inserted into the ESM monolayer, the inherent intramolecular hydrogen bonds between the phosphate moiety and 3OH in the sphingosine backbones are destroyed. 35839485 6 30 theme long 918:921 arg1 chain 928:932 the N-linked long acid chain 905:932 the N-linked long acid chain 905:932 During this process, the sphingosine backbones become more ordered, while the conformation of the N-linked long acid chain remains unaltered. 35839485 7 31 theme -PO-2 1060:1064 arg1 parallel 1104:1111 parallel 1104:1111 parallel 1104:1111 The OH of the cholesterol head group can bind to the -PO-2 of the ESM molecule, and the orientation of the -PO-2 in the head groups changes to be more parallel to the interface. 35839485 7 31 theme -PO-2 1060:1064 arg1 orientation 1041:1051 the orientation 1037:1051 the orientation of the -PO-2 in the head groups 1037:1083 The OH of the cholesterol head group can bind to the -PO-2 of the ESM molecule, and the orientation of the -PO-2 in the head groups changes to be more parallel to the interface. 35839485 1 32 theme frequency 243:251 arg1 spectroscopy 276:287 high-resolution broadband sum frequency generation vibrational spectroscopy 213:287 high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) 213:302 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 1 32 theme frequency 243:251 arg1 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 6 33 theme N-linked 909:916 arg1 chain 928:932 the N-linked long acid chain 905:932 the N-linked long acid chain 905:932 During this process, the sphingosine backbones become more ordered, while the conformation of the N-linked long acid chain remains unaltered. 35839485 0 34 theme Conformational 53:66 arg1 Changes 68:74 Sphingomyelin Conformational Changes 39:74 Sphingomyelin Conformational Changes 39:74 Mechanism by Which Cholesterol Induces Sphingomyelin Conformational Changes at an Air/Water Interface. 35839485 5 35 theme phosphate 742:750 arg1 moiety 752:757 the phosphate moiety 738:757 the phosphate moiety 738:757 When cholesterol is inserted into the ESM monolayer, the inherent intramolecular hydrogen bonds between the phosphate moiety and 3OH in the sphingosine backbones are destroyed. 35839485 1 36 theme sphingomyelin 162:174 arg1 monolayers 176:185 cholesterol and sphingomyelin monolayers 146:185 cholesterol and sphingomyelin monolayers 146:185 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 7 37 from orientation 1041:1051 arg1 groups 1078:1083 the head groups 1069:1083 the head groups 1069:1083 The OH of the cholesterol head group can bind to the -PO-2 of the ESM molecule, and the orientation of the -PO-2 in the head groups changes to be more parallel to the interface. 35839485 6 38 link N-linked 909:916 arg1 chain 928:932 the N-linked long acid chain 905:932 the N-linked long acid chain 905:932 During this process, the sphingosine backbones become more ordered, while the conformation of the N-linked long acid chain remains unaltered. 35839485 7 39 theme group 984:988 arg1 OH 957:958 The OH 953:958 The OH of the cholesterol head group 953:988 The OH of the cholesterol head group can bind to the -PO-2 of the ESM molecule, and the orientation of the -PO-2 in the head groups changes to be more parallel to the interface. 35839485 7 40 theme cholesterol 967:977 arg1 group 984:988 the cholesterol head group 963:988 the cholesterol head group 963:988 The OH of the cholesterol head group can bind to the -PO-2 of the ESM molecule, and the orientation of the -PO-2 in the head groups changes to be more parallel to the interface. 35839485 1 41 theme generation 253:262 arg1 spectroscopy 276:287 high-resolution broadband sum frequency generation vibrational spectroscopy 213:287 high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) 213:302 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 1 41 theme generation 253:262 arg1 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 3 42 theme air/water 586:594 arg1 interface 596:604 an air/water interface 583:604 an air/water interface 583:604 The analysis of the spectra shows that cholesterol can induce sphingomyelin conformational changes at an air/water interface. 35839485 1 43 from level 204:208 arg1 interactions 130:141 the interactions 126:141 the interactions in cholesterol and sphingomyelin monolayers at the molecular level 126:208 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 1 44 theme cholesterol 146:156 arg1 monolayers 176:185 cholesterol and sphingomyelin monolayers 146:185 cholesterol and sphingomyelin monolayers 146:185 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 1 45 theme vibrational 264:274 arg1 spectroscopy 276:287 high-resolution broadband sum frequency generation vibrational spectroscopy 213:287 high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) 213:302 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 1 45 theme vibrational 264:274 arg1 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 1 46 theme high-resolution 213:227 arg1 spectroscopy 276:287 high-resolution broadband sum frequency generation vibrational spectroscopy 213:287 high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) 213:302 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 1 46 theme high-resolution 213:227 arg1 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 HR-BB-SFG-VS 290:301 This work investigates the interactions in cholesterol and sphingomyelin monolayers at the molecular level by high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). 35839485 2 47 theme concentration 385:397 arg1 function 361:368 a function 359:368 a function of cholesterol concentration 359:397 The SFG spectra of natural egg sphingomyelin (ESM) as a function of cholesterol concentration are obtained at an air/water interface under different polarization combinations. 35764435 5 0 gly glycopeptides 852:864 arg2 glycopeptides 852:864 1598 N-linked glycopeptides 838:864 1598 N-linked glycopeptides 838:864 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 4 1 dep not 638:640 arg1 so 647:648 so 647:648 so 647:648 While most studies focused on improving the affinity of the boronic acids to the sugars, we discovered that the buffer choice is just as important for successful enrichment if not more so. 35764435 3 2 gly glycopeptides 403:415 arg2 glycopeptides 403:415 glycopeptides 403:415 glycopeptides 403:415 Among the methods used for the enrichment of glycopeptides, boronic acid never lived up to its promise. 35764435 4 3 theme most 468:471 arg1 studies 473:479 most studies 468:479 most studies 468:479 While most studies focused on improving the affinity of the boronic acids to the sugars, we discovered that the buffer choice is just as important for successful enrichment if not more so. 35764435 1 4 theme posttranslational 105:121 arg1 modifications 123:135 posttranslational modifications 105:135 posttranslational modifications that play a crucial role in many biological pathways and diseases 105:201 Protein glycosylation is a family of posttranslational modifications that play a crucial role in many biological pathways and diseases. 35764435 5 5 gly glycopeptides 794:806 arg2 glycopeptides 794:806 total quantified glycopeptides 777:806 total quantified glycopeptides 777:806 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 1 6 theme Protein 68:74 arg1 glycosylation 76:88 Protein glycosylation 68:88 Protein glycosylation 68:88 Protein glycosylation is a family of posttranslational modifications that play a crucial role in many biological pathways and diseases. 35764435 1 6 theme Protein 68:74 arg1 family 95:100 a family 93:100 a family of posttranslational modifications that play a crucial role in many biological pathways and diseases 93:201 Protein glycosylation is a family of posttranslational modifications that play a crucial role in many biological pathways and diseases. 35764435 1 7 theme many 165:168 arg1 pathways 181:188 many biological pathways 165:188 many biological pathways 165:188 Protein glycosylation is a family of posttranslational modifications that play a crucial role in many biological pathways and diseases. 35764435 5 8 theme brain 750:754 arg1 specimens 756:764 human plasma and brain specimens 733:764 human plasma and brain specimens 733:764 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 5 9 dep brain 873:877 arg1 the 869:871 the 869:871 the 869:871 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 2 10 theme modifications 260:272 arg1 family 250:255 such a diverse family 235:255 such a diverse family of modifications 235:272 The enrichment and analysis of such a diverse family of modifications are very challenging because of the number of possible glycan-peptide combinations. 35764435 1 11 theme biological 170:179 arg1 pathways 181:188 many biological pathways 165:188 many biological pathways 165:188 Protein glycosylation is a family of posttranslational modifications that play a crucial role in many biological pathways and diseases. 35764435 0 12 theme Glycopeptide 10:21 arg1 Method-It 34:42 Optimized Glycopeptide Enrichment Method-It 0:42 Optimized Glycopeptide Enrichment Method-It 0:42 Optimized Glycopeptide Enrichment Method-It Is All About the Sauce. 35764435 5 13 from 737 883:885 arg1 plasma 902:907 nondepleted plasma 890:907 nondepleted plasma 890:907 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 0 14 theme Optimized 0:8 arg1 Method-It 34:42 Optimized Glycopeptide Enrichment Method-It 0:42 Optimized Glycopeptide Enrichment Method-It 0:42 Optimized Glycopeptide Enrichment Method-It Is All About the Sauce. 35764435 5 15 theme nondepleted 890:900 arg1 plasma 902:907 nondepleted plasma 890:907 nondepleted plasma 890:907 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 3 16 dep promise 453:459 arg1 up 443:444 up 443:444 up 443:444 Among the methods used for the enrichment of glycopeptides, boronic acid never lived up to its promise. 35764435 5 17 from brain 873:877 arg1 plasma 902:907 nondepleted plasma 890:907 nondepleted plasma 890:907 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 5 18 theme quantified 783:792 arg1 glycopeptides 794:806 total quantified glycopeptides 777:806 total quantified glycopeptides 777:806 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 0 19 theme Enrichment 23:32 arg1 Method-It 34:42 Optimized Glycopeptide Enrichment Method-It 0:42 Optimized Glycopeptide Enrichment Method-It 0:42 Optimized Glycopeptide Enrichment Method-It Is All About the Sauce. 35764435 5 20 theme human 733:737 arg1 specimens 756:764 human plasma and brain specimens 733:764 human plasma and brain specimens 733:764 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 2 21 theme glycan-peptide 329:342 arg1 combinations 344:355 possible glycan-peptide combinations 320:355 possible glycan-peptide combinations 320:355 The enrichment and analysis of such a diverse family of modifications are very challenging because of the number of possible glycan-peptide combinations. 35764435 5 22 theme amine-less 667:676 arg1 buffer 678:683 an amine-less buffer 664:683 an amine-less buffer 664:683 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 4 23 theme successful 613:622 arg1 enrichment 624:633 successful enrichment 613:633 successful enrichment 613:633 While most studies focused on improving the affinity of the boronic acids to the sugars, we discovered that the buffer choice is just as important for successful enrichment if not more so. 35764435 3 24 theme boronic 418:424 arg1 acid 426:429 boronic acid 418:429 boronic acid 418:429 Among the methods used for the enrichment of glycopeptides, boronic acid never lived up to its promise. 35764435 5 25 link N-linked 843:850 arg1 glycopeptides 852:864 1598 N-linked glycopeptides 838:864 1598 N-linked glycopeptides 838:864 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 6 26 theme boronic 964:970 arg1 binding 977:983 boronic acid binding 964:983 boronic acid binding 964:983 We speculate that amines compete with the glycans for boronic acid binding, and therefore the elimination of them improved the method significantly. 35764435 5 27 theme best 700:703 arg1 coverage 720:727 the best glycoproteomic coverage 696:727 the best glycoproteomic coverage 696:727 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 5 28 theme total 777:781 arg1 glycopeptides 794:806 total quantified glycopeptides 777:806 total quantified glycopeptides 777:806 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 2 29 theme combinations 344:355 arg1 number 310:315 the number 306:315 the number of possible glycan-peptide combinations 306:355 The enrichment and analysis of such a diverse family of modifications are very challenging because of the number of possible glycan-peptide combinations. 35764435 3 30 theme glycopeptides 403:415 arg1 enrichment 389:398 the enrichment 385:398 the enrichment of glycopeptides 385:415 Among the methods used for the enrichment of glycopeptides, boronic acid never lived up to its promise. 35764435 4 31 theme acids 530:534 arg1 affinity 506:513 the affinity 502:513 the affinity of the boronic acids to the sugars 502:548 While most studies focused on improving the affinity of the boronic acids to the sugars, we discovered that the buffer choice is just as important for successful enrichment if not more so. 35764435 1 32 theme modifications 123:135 arg1 glycosylation 76:88 Protein glycosylation 68:88 Protein glycosylation 68:88 Protein glycosylation is a family of posttranslational modifications that play a crucial role in many biological pathways and diseases. 35764435 1 32 theme modifications 123:135 arg1 family 95:100 a family 93:100 a family of posttranslational modifications that play a crucial role in many biological pathways and diseases 93:201 Protein glycosylation is a family of posttranslational modifications that play a crucial role in many biological pathways and diseases. 35764435 4 33 theme boronic 522:528 arg1 acids 530:534 the boronic acids 518:534 the boronic acids 518:534 While most studies focused on improving the affinity of the boronic acids to the sugars, we discovered that the buffer choice is just as important for successful enrichment if not more so. 35764435 6 34 theme acid 972:975 arg1 binding 977:983 boronic acid binding 964:983 boronic acid binding 964:983 We speculate that amines compete with the glycans for boronic acid binding, and therefore the elimination of them improved the method significantly. 35764435 2 35 theme possible 320:327 arg1 combinations 344:355 possible glycan-peptide combinations 320:355 possible glycan-peptide combinations 320:355 The enrichment and analysis of such a diverse family of modifications are very challenging because of the number of possible glycan-peptide combinations. 35764435 4 36 dep so 647:648 arg1 more 642:645 more 642:645 more 642:645 While most studies focused on improving the affinity of the boronic acids to the sugars, we discovered that the buffer choice is just as important for successful enrichment if not more so. 35764435 2 37 theme family 250:255 arg1 analysis 223:230 analysis 223:230 analysis 223:230 The enrichment and analysis of such a diverse family of modifications are very challenging because of the number of possible glycan-peptide combinations. 35764435 2 37 theme family 250:255 arg1 enrichment 208:217 enrichment 208:217 enrichment 208:217 The enrichment and analysis of such a diverse family of modifications are very challenging because of the number of possible glycan-peptide combinations. 35764435 5 38 theme N-linked 843:850 arg1 glycopeptides 852:864 1598 N-linked glycopeptides 838:864 1598 N-linked glycopeptides 838:864 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 4 39 theme buffer 574:579 arg1 choice 581:586 the buffer choice 570:586 the buffer choice 570:586 While most studies focused on improving the affinity of the boronic acids to the sugars, we discovered that the buffer choice is just as important for successful enrichment if not more so. 35764435 4 39 theme buffer 574:579 arg1 important 599:607 important 599:607 important 599:607 While most studies focused on improving the affinity of the boronic acids to the sugars, we discovered that the buffer choice is just as important for successful enrichment if not more so. 35764435 5 40 theme glycoproteomic 705:718 arg1 coverage 720:727 the best glycoproteomic coverage 696:727 the best glycoproteomic coverage 696:727 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 2 41 theme diverse 242:248 arg1 family 250:255 such a diverse family 235:255 such a diverse family of modifications 235:272 The enrichment and analysis of such a diverse family of modifications are very challenging because of the number of possible glycan-peptide combinations. 35764435 6 42 theme them 1019:1022 arg1 elimination 1004:1014 the elimination 1000:1014 the elimination of them 1000:1022 We speculate that amines compete with the glycans for boronic acid binding, and therefore the elimination of them improved the method significantly. 35764435 2 43 dep enrichment 208:217 arg1 The 204:206 The 204:206 The 204:206 The enrichment and analysis of such a diverse family of modifications are very challenging because of the number of possible glycan-peptide combinations. 35764435 5 44 theme plasma 739:744 arg1 specimens 756:764 human plasma and brain specimens 733:764 human plasma and brain specimens 733:764 We show that an amine-less buffer allows for the best glycoproteomic coverage, in human plasma and brain specimens, improving total quantified glycopeptides by over 10-fold, and reaching 1598 N-linked glycopeptides in the brain and 737 in nondepleted plasma. 35764435 1 45 theme crucial 149:155 arg1 role 157:160 a crucial role 147:160 a crucial role 147:160 Protein glycosylation is a family of posttranslational modifications that play a crucial role in many biological pathways and diseases. 36875753 5 0 link patient-derived 984:998 arg1 organoids 1009:1017 NGLY1 patient-derived midbrain organoids 978:1017 NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA 978:1050 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 3 1 theme patient-derived 548:562 arg1 iPSCs 564:568 patient-derived iPSCs 548:568 patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs 548:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 3 2 theme knockout 742:749 arg1 iPSCs 751:755 generated NGLY1 knockout iPSCs 726:755 generated NGLY1 knockout iPSCs 726:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 1 3 link N-linked 224:231 arg1 glycan 233:238 N-linked glycan 224:238 N-linked glycan 224:238 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 5 4 theme protein 946:952 arg1 markers 954:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers 888:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers 888:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 2 5 theme liver 373:377 arg1 dysfunction 379:389 liver dysfunction 373:389 liver dysfunction 373:389 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 7 6 theme deficiency 1338:1347 arg1 treatments 1318:1327 treatments 1318:1327 treatments of NGLY1 deficiency 1318:1347 These results provide a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency. 36875753 3 7 theme distinct 593:600 arg1 mutations-one 618:630 distinct disease-causing mutations-one 593:630 distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs 593:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 3 8 theme homozygous 632:641 arg1 mutations-one 618:630 distinct disease-causing mutations-one 593:630 distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs 593:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 3 9 theme disease-causing 602:616 arg1 mutations-one 618:630 distinct disease-causing mutations-one 593:630 distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs 593:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 1 10 theme NGLY1 77:81 arg1 deficiency 83:92 NGLY1 deficiency 77:92 NGLY1 deficiency 77:92 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 1 10 theme NGLY1 77:81 arg1 disease 140:146 an ultra-rare, autosomal recessive genetic disease 97:146 disease 140:146 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 7 11 theme NGLY1 1234:1238 arg1 model 1248:1252 a relevant NGLY1 disease model 1223:1252 a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency 1223:1347 These results provide a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency. 36875753 2 12 theme clinical 298:305 arg1 disorder 360:367 motor disorder 354:367 motor disorder 354:367 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 12 theme clinical 298:305 arg1 dysfunction 379:389 liver dysfunction 373:389 liver dysfunction 373:389 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 12 theme clinical 298:305 arg1 symptoms 307:314 complex clinical symptoms 290:314 complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction 290:389 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 12 theme clinical 298:305 arg1 delay 347:351 global developmental delay 326:351 global developmental delay 326:351 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 5 13 theme NGLY1 978:982 arg1 organoids 1009:1017 NGLY1 patient-derived midbrain organoids 978:1017 NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA 978:1050 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 3 14 dep pathogenesis 425:436 arg1 the 413:415 the 413:415 the 413:415 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 1 15 from mutations 158:166 arg1 gene 181:184 the NGLY1 gene 171:184 the NGLY1 gene encoding N-glycanase one that removes N-linked glycan 171:238 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 2 16 theme complex 290:296 arg1 disorder 360:367 motor disorder 354:367 motor disorder 354:367 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 16 theme complex 290:296 arg1 dysfunction 379:389 liver dysfunction 373:389 liver dysfunction 373:389 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 16 theme complex 290:296 arg1 symptoms 307:314 complex clinical symptoms 290:314 complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction 290:389 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 16 theme complex 290:296 arg1 delay 347:351 global developmental delay 326:351 global developmental delay 326:351 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 6 17 theme significant 1144:1154 arg1 reduction 1156:1164 a significant reduction 1142:1164 a significant reduction in patient iPSC derived organoids 1142:1198 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 1 18 theme NGLY1 175:179 arg1 gene 181:184 the NGLY1 gene 171:184 the NGLY1 gene encoding N-glycanase one that removes N-linked glycan 171:238 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 7 19 theme relevant 1225:1232 arg1 model 1248:1252 a relevant NGLY1 disease model 1223:1252 a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency 1223:1347 These results provide a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency. 36875753 3 20 with patients 579:586 arg1 mutations-one 618:630 distinct disease-causing mutations-one 593:630 distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs 593:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 7 21 theme disease 1269:1275 arg1 mechanisms 1277:1286 disease mechanisms 1269:1286 disease mechanisms 1269:1286 These results provide a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency. 36875753 6 22 theme patient 1169:1175 arg1 iPSC 1177:1180 patient iPSC 1169:1180 patient iPSC 1169:1180 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 3 23 theme NGLY1 475:479 arg1 deficiency 481:490 the NGLY1 deficiency 471:490 the NGLY1 deficiency 471:490 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 6 24 dep derived 1182:1188 arg1 iPSC 1177:1180 patient iPSC 1169:1180 patient iPSC 1169:1180 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 5 25 theme patient-derived 984:998 arg1 organoids 1009:1017 NGLY1 patient-derived midbrain organoids 978:1017 NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA 978:1050 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 5 26 theme astrocytic 913:922 arg1 markers 954:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers 888:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers 888:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 3 27 theme disease 417:423 arg1 pathogenesis 425:436 disease pathogenesis 417:436 disease pathogenesis 417:436 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 2 28 contain have 285:288 arg1 Patients 241:248 Patients 241:248 Patients with pathogenic mutations in NGLY1 241:283 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 28 contain have 285:288 arg2 delay 347:351 global developmental delay 326:351 global developmental delay 326:351 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 28 contain have 285:288 arg2 dysfunction 379:389 liver dysfunction 373:389 liver dysfunction 373:389 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 28 contain have 285:288 arg2 symptoms 307:314 complex clinical symptoms 290:314 complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction 290:389 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 28 contain have 285:288 arg2 disorder 360:367 motor disorder 354:367 motor disorder 354:367 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 0 29 link patient-derived 41:55 arg1 organoids 66:74 NGLY1 patient-derived midbrain organoids 35:74 NGLY1 patient-derived midbrain organoids 35:74 Generation and characterization of NGLY1 patient-derived midbrain organoids. 36875753 2 30 theme developmental 333:345 arg1 delay 347:351 global developmental delay 326:351 global developmental delay 326:351 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 2 31 from mutations 266:274 arg1 NGLY1 279:283 NGLY1 279:283 NGLY1 279:283 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 5 32 theme glial 924:928 arg1 protein 946:952 glial fibrillary acid protein 924:952 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers 888:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 4 33 theme midbrain 794:801 arg1 organoids 803:811 NGLY1 deficient midbrain organoids 778:811 NGLY1 deficient midbrain organoids 778:811 We demonstrate that NGLY1 deficient midbrain organoids show altered neuronal development compared to one wild type (WT) organoid. 36875753 3 34 link patient-derived 548:562 arg1 iPSCs 564:568 patient-derived iPSCs 548:568 patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs 548:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 6 35 from reduction 1156:1164 arg1 organoids 1190:1198 patient iPSC derived organoids 1169:1198 patient iPSC derived organoids 1169:1198 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 2 36 theme global 326:331 arg1 delay 347:351 global developmental delay 326:351 global developmental delay 326:351 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 1 37 theme ultra-rare 100:109 arg1 disease 140:146 an ultra-rare, autosomal recessive genetic disease 97:146 disease 140:146 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 1 37 theme ultra-rare 100:109 arg1 deficiency 83:92 NGLY1 deficiency 77:92 NGLY1 deficiency 77:92 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 5 38 theme midbrain 1000:1007 arg1 organoids 1009:1017 NGLY1 patient-derived midbrain organoids 978:1017 NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA 978:1050 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 1 39 theme autosomal 112:120 arg1 disease 140:146 an ultra-rare, autosomal recessive genetic disease 97:146 disease 140:146 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 1 39 theme autosomal 112:120 arg1 deficiency 83:92 NGLY1 deficiency 77:92 NGLY1 deficiency 77:92 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 7 40 theme disease 1240:1246 arg1 model 1248:1252 a relevant NGLY1 disease model 1223:1252 a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency 1223:1347 These results provide a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency. 36875753 5 41 theme neuronal 893:900 arg1 markers 954:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers 888:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers 888:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 0 42 theme patient-derived 41:55 arg1 organoids 66:74 NGLY1 patient-derived midbrain organoids 35:74 NGLY1 patient-derived midbrain organoids 35:74 Generation and characterization of NGLY1 patient-derived midbrain organoids. 36875753 2 43 with Patients 241:248 arg1 mutations 266:274 pathogenic mutations 255:274 pathogenic mutations in NGLY1 255:283 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 4 44 theme type 868:871 arg1 organoid 878:885 one wild type (WT) organoid 859:885 one wild type (WT) organoid 859:885 We demonstrate that NGLY1 deficient midbrain organoids show altered neuronal development compared to one wild type (WT) organoid. 36875753 3 45 theme deficiency 481:490 arg1 symptoms 459:466 the neurological symptoms 442:466 the neurological symptoms 442:466 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 3 45 theme deficiency 481:490 arg1 pathogenesis 425:436 disease pathogenesis 417:436 disease pathogenesis 417:436 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 0 46 theme NGLY1 35:39 arg1 organoids 66:74 NGLY1 patient-derived midbrain organoids 35:74 NGLY1 patient-derived midbrain organoids 35:74 Generation and characterization of NGLY1 patient-derived midbrain organoids. 36875753 3 47 theme neurological 446:457 arg1 symptoms 459:466 the neurological symptoms 442:466 the neurological symptoms 442:466 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 4 48 theme neuronal 826:833 arg1 development 835:845 altered neuronal development 818:845 altered neuronal development 818:845 We demonstrate that NGLY1 deficient midbrain organoids show altered neuronal development compared to one wild type (WT) organoid. 36875753 3 49 theme other 661:665 arg1 Q208X 650:654 p. Q208X 647:654 p. Q208X 647:654 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 3 49 theme other 661:665 arg1 compound 667:674 the other compound 657:674 the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs 657:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 1 50 theme N-linked 224:231 arg1 glycan 233:238 N-linked glycan 224:238 N-linked glycan 224:238 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 0 51 theme organoids 66:74 arg1 characterization 15:30 characterization 15:30 characterization 15:30 Generation and characterization of NGLY1 patient-derived midbrain organoids. 36875753 0 51 theme organoids 66:74 arg1 Generation 0:9 Generation 0:9 Generation 0:9 Generation and characterization of NGLY1 patient-derived midbrain organoids. 36875753 6 52 theme tyrosine 1111:1118 arg1 marker 1103:1108 dopaminergic neuronal marker 1081:1108 dopaminergic neuronal marker 1081:1108 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 6 52 theme tyrosine 1111:1118 arg1 hydroxylase 1120:1130 tyrosine hydroxylase 1111:1130 tyrosine hydroxylase 1111:1130 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 5 53 theme neurotransmitter 1030:1045 arg1 GABA 1047:1050 neurotransmitter GABA 1030:1050 neurotransmitter GABA 1030:1050 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 6 54 theme derived 1182:1188 arg1 organoids 1190:1198 patient iPSC derived organoids 1169:1198 patient iPSC derived organoids 1169:1198 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 1 55 theme recessive 122:130 arg1 disease 140:146 an ultra-rare, autosomal recessive genetic disease 97:146 disease 140:146 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 1 55 theme recessive 122:130 arg1 deficiency 83:92 NGLY1 deficiency 77:92 NGLY1 deficiency 77:92 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 0 56 theme midbrain 57:64 arg1 organoids 66:74 NGLY1 patient-derived midbrain organoids 35:74 NGLY1 patient-derived midbrain organoids 35:74 Generation and characterization of NGLY1 patient-derived midbrain organoids. 36875753 3 57 theme generated 726:734 arg1 iPSCs 751:755 generated NGLY1 knockout iPSCs 726:755 generated NGLY1 knockout iPSCs 726:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 5 58 dep neuronal 893:900 arg1 TUJ1 903:906 TUJ1 903:906 TUJ1 903:906 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 1 59 theme genetic 132:138 arg1 disease 140:146 an ultra-rare, autosomal recessive genetic disease 97:146 disease 140:146 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 1 59 theme genetic 132:138 arg1 deficiency 83:92 NGLY1 deficiency 77:92 NGLY1 deficiency 77:92 NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. 36875753 3 60 theme heterozygous 676:687 arg1 Q208X 650:654 p. Q208X 647:654 p. Q208X 647:654 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 3 60 theme heterozygous 676:687 arg1 compound 667:674 the other compound 657:674 the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs 657:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 3 61 theme NGLY1 736:740 arg1 iPSCs 751:755 generated NGLY1 knockout iPSCs 726:755 generated NGLY1 knockout iPSCs 726:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 4 62 theme wild 863:866 arg1 type 868:871 one wild type 859:871 one wild type (WT) organoid 859:885 We demonstrate that NGLY1 deficient midbrain organoids show altered neuronal development compared to one wild type (WT) organoid. 36875753 4 62 theme wild 863:866 arg1 WT 874:875 WT 874:875 WT 874:875 We demonstrate that NGLY1 deficient midbrain organoids show altered neuronal development compared to one wild type (WT) organoid. 36875753 2 63 theme motor 354:358 arg1 disorder 360:367 motor disorder 354:367 motor disorder 354:367 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 4 64 theme altered 818:824 arg1 development 835:845 altered neuronal development 818:845 altered neuronal development 818:845 We demonstrate that NGLY1 deficient midbrain organoids show altered neuronal development compared to one wild type (WT) organoid. 36875753 3 65 dep L318P 696:700 arg1 iPSCs 751:755 generated NGLY1 knockout iPSCs 726:755 generated NGLY1 knockout iPSCs 726:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 3 66 theme midbrain 523:530 arg1 organoids 532:540 midbrain organoids 523:540 midbrain organoids 523:540 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 4 67 theme deficient 784:792 arg1 organoids 803:811 NGLY1 deficient midbrain organoids 778:811 NGLY1 deficient midbrain organoids 778:811 We demonstrate that NGLY1 deficient midbrain organoids show altered neuronal development compared to one wild type (WT) organoid. 36875753 6 68 link derived 1182:1188 arg1 organoids 1190:1198 patient iPSC derived organoids 1169:1198 patient iPSC derived organoids 1169:1198 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 3 69 dep generated 495:503 arg1 understand 402:411 understand 402:411 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency 392:490 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 5 70 theme fibrillary 930:939 arg1 protein 946:952 glial fibrillary acid protein 924:952 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers 888:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 6 71 theme neuronal 1094:1101 arg1 marker 1103:1108 dopaminergic neuronal marker 1081:1108 dopaminergic neuronal marker 1081:1108 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 6 71 theme neuronal 1094:1101 arg1 hydroxylase 1120:1130 tyrosine hydroxylase 1111:1130 tyrosine hydroxylase 1111:1130 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 7 72 theme NGLY1 1332:1336 arg1 deficiency 1338:1347 NGLY1 deficiency 1332:1347 NGLY1 deficiency 1332:1347 These results provide a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency. 36875753 2 73 theme pathogenic 255:264 arg1 mutations 266:274 pathogenic mutations 255:274 pathogenic mutations in NGLY1 255:283 Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. 36875753 5 74 theme acid 941:944 arg1 protein 946:952 glial fibrillary acid protein 924:952 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers 888:960 Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. 36875753 3 75 from patients 579:586 arg1 iPSCs 564:568 patient-derived iPSCs 548:568 patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs 548:755 To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. 36875753 6 76 theme dopaminergic 1081:1092 arg1 marker 1103:1108 dopaminergic neuronal marker 1081:1108 dopaminergic neuronal marker 1081:1108 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36875753 6 76 theme dopaminergic 1081:1092 arg1 hydroxylase 1120:1130 tyrosine hydroxylase 1111:1130 tyrosine hydroxylase 1111:1130 Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. 36244453 3 0 theme N-terminal 668:677 arg1 subunits 702:709 the receptor subunits 689:709 the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER 689:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 3 0 theme N-terminal 668:677 arg1 domain 679:684 the extracellular N-terminal domain 650:684 the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER 650:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 2 1 theme surface 336:342 arg1 expression 344:353 Cell surface expression 331:353 Cell surface expression of GABAARs, a prerequisite for their function, 331:400 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 7 2 with binding 1446:1452 arg1 calnexin 1428:1435 calnexin 1428:1435 calnexin 1428:1435 When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. 36244453 7 2 with binding 1446:1452 arg1 Grp94 1493:1497 Grp94 1493:1497 Grp94 1493:1497 When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. 36244453 1 3 theme GABA-gated 228:237 arg1 channels 253:260 pentameric GABA-gated Cl-/HCO3- ion channels 217:260 pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system 217:328 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 7 4 theme similar 1438:1444 arg1 binding 1446:1452 similar binding 1438:1452 similar binding to BiP 1438:1459 When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. 36244453 4 5 theme subunit 1028:1034 arg1 assembly 1036:1043 the subunit assembly 1024:1043 the subunit assembly 1024:1043 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 8 6 theme first 1670:1674 arg1 domain 1690:1695 the first transmembrane domain 1666:1695 the first transmembrane domain 1666:1695 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 1 7 theme ion 249:251 arg1 channels 253:260 pentameric GABA-gated Cl-/HCO3- ion channels 217:260 pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system 217:328 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 4 8 theme region 833:838 arg1 Modifications 811:823 Modifications 811:823 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis 811:914 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 3 9 theme receptor 693:700 arg1 subunits 702:709 the receptor subunits 689:709 the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER 689:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 1 10 theme A 153:153 arg1 GABAARs 186:192 GABAARs 186:192 GABAARs 186:192 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 1 10 theme A 153:153 arg1 receptors 175:183 Type A γ-aminobutyric acid receptors 148:183 Type A γ-aminobutyric acid receptors (GABAARs) 148:193 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 6 11 theme surface 1192:1198 arg1 expression 1200:1209 their surface expression 1186:1209 their surface expression 1186:1209 However, their surface expression was increased when ER-associated degradation or proteosome function was inhibited, while modulation of ER calcium stores had little effect. 36244453 7 12 with association 1476:1486 arg1 calnexin 1428:1435 calnexin 1428:1435 calnexin 1428:1435 When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. 36244453 7 12 with association 1476:1486 arg1 Grp94 1493:1497 Grp94 1493:1497 Grp94 1493:1497 When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. 36244453 1 13 theme acid 170:173 arg1 GABAARs 186:192 GABAARs 186:192 GABAARs 186:192 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 1 13 theme acid 170:173 arg1 receptors 175:183 Type A γ-aminobutyric acid receptors 148:183 Type A γ-aminobutyric acid receptors (GABAARs) 148:193 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 4 14 contain had 1007:1009 arg2 effect 1014:1019 no effect 1011:1019 no effect 1011:1019 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 4 14 contain had 1007:1009 arg1 they 1002:1005 they 1002:1005 they 1002:1005 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 3 15 theme first 725:729 arg1 domain 745:750 the first transmembrane domain 721:750 the first transmembrane domain 721:750 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 8 16 theme adjoining 1656:1664 arg1 region 1649:1654 the conserved region 1635:1654 the conserved region adjoining the first transmembrane domain 1635:1695 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 3 17 theme important 764:772 arg1 region 757:762 a region 755:762 a region important for GABAAR processing within the ER 755:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 4 18 from trafficking 932:942 arg1 systems 985:991 heterologous cell systems 967:991 heterologous cell systems 967:991 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 4 19 theme γ2 859:860 arg1 subunits 862:869 the α1, β3, and γ2 subunits 843:869 the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis 843:914 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 0 20 from end 83:85 arg1 region 69:74 a conserved region 57:74 a conserved region at the end of the N-terminal extracellular domain of receptor subunits 57:145 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 6 21 theme proteosome 1259:1268 arg1 function 1270:1277 proteosome function 1259:1277 proteosome function 1259:1277 However, their surface expression was increased when ER-associated degradation or proteosome function was inhibited, while modulation of ER calcium stores had little effect. 36244453 4 22 theme cell 951:954 arg1 surface 956:962 the cell surface 947:962 the cell surface 947:962 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 3 23 theme GABAAR 778:783 arg1 processing 785:794 GABAAR processing 778:794 GABAAR processing within the ER 778:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 1 24 theme nervous 315:321 arg1 system 323:328 the central nervous system 303:328 the central nervous system 303:328 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 8 25 with interaction 1532:1542 arg1 GABAAR 1567:1572 the wt or mutated GABAAR 1549:1572 the wt or mutated GABAAR 1549:1572 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 0 26 theme subunits 138:145 arg1 domain 119:124 the N-terminal extracellular domain 90:124 the N-terminal extracellular domain of receptor subunits 90:145 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 0 26 theme subunits 138:145 arg1 subunits 138:145 receptor subunits 129:145 receptor subunits 129:145 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 0 27 theme conserved 59:67 arg1 region 69:74 a conserved region 57:74 a conserved region at the end of the N-terminal extracellular domain of receptor subunits 57:145 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 4 28 theme β3 851:852 arg1 subunits 862:869 the α1, β3, and γ2 subunits 843:869 the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis 843:914 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 4 29 theme GABAAR 925:930 arg1 trafficking 932:942 GABAAR trafficking 925:942 GABAAR trafficking to the cell surface in heterologous cell systems 925:991 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 5 30 dep chaperones 1140:1149 arg1 chaperones 1140:1149 chaperones calnexin, BiP, and Grp94 1140:1174 chaperones calnexin, BiP, and Grp94 1140:1174 We found that mutated receptors accumulated in the ER where they were shown to associate with chaperones calnexin, BiP, and Grp94. 36244453 5 30 dep chaperones 1140:1149 arg1 BiP 1161:1163 BiP 1161:1163 BiP 1161:1163 We found that mutated receptors accumulated in the ER where they were shown to associate with chaperones calnexin, BiP, and Grp94. 36244453 5 30 dep chaperones 1140:1149 arg1 Grp94 1170:1174 Grp94 1170:1174 Grp94 1170:1174 We found that mutated receptors accumulated in the ER where they were shown to associate with chaperones calnexin, BiP, and Grp94. 36244453 5 30 dep chaperones 1140:1149 arg1 calnexin 1151:1158 calnexin 1151:1158 calnexin 1151:1158 We found that mutated receptors accumulated in the ER where they were shown to associate with chaperones calnexin, BiP, and Grp94. 36244453 6 31 theme stores 1325:1330 arg1 modulation 1300:1309 modulation 1300:1309 modulation of ER calcium stores 1300:1330 However, their surface expression was increased when ER-associated degradation or proteosome function was inhibited, while modulation of ER calcium stores had little effect. 36244453 5 32 theme mutated 1060:1066 arg1 receptors 1068:1076 mutated receptors 1060:1076 mutated receptors 1060:1076 We found that mutated receptors accumulated in the ER where they were shown to associate with chaperones calnexin, BiP, and Grp94. 36244453 6 33 theme ER 1314:1315 arg1 stores 1325:1330 ER calcium stores 1314:1330 ER calcium stores 1314:1330 However, their surface expression was increased when ER-associated degradation or proteosome function was inhibited, while modulation of ER calcium stores had little effect. 36244453 2 34 theme receptor 450:457 arg1 subunits 459:466 the receptor subunits 446:466 the receptor subunits 446:466 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 2 35 theme appropriate 422:432 arg1 assembly 434:441 the appropriate assembly 418:441 the appropriate assembly of the receptor subunits 418:466 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 2 36 theme transient 478:486 arg1 interactions 488:499 their transient interactions 472:499 their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus 472:583 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 1 37 theme channels 253:260 arg1 family 207:212 a family 205:212 a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system 205:328 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 8 38 theme Structural 1500:1509 arg1 modeling 1511:1518 Structural modeling 1500:1518 Structural modeling of calnexin interaction with the wt or mutated GABAAR 1500:1572 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 6 39 theme little 1336:1341 arg1 effect 1343:1348 little effect 1336:1348 little effect 1336:1348 However, their surface expression was increased when ER-associated degradation or proteosome function was inhibited, while modulation of ER calcium stores had little effect. 36244453 0 40 theme cell 11:14 arg1 expression 24:33 cell surface expression 11:33 cell surface expression of GABAA receptors 11:52 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 4 41 theme cell 980:983 arg1 systems 985:991 heterologous cell systems 967:991 heterologous cell systems 967:991 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 3 42 theme acid 629:632 arg1 sequence 634:641 a highly conserved amino acid sequence 604:641 a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER 604:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 0 43 theme expression 24:33 arg1 Control 0:6 Control 0:6 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 0:146 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 8 44 theme interaction 1532:1542 arg1 modeling 1511:1518 Structural modeling 1500:1518 Structural modeling of calnexin interaction with the wt or mutated GABAAR 1500:1572 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 3 45 theme conserved 613:621 arg1 sequence 634:641 a highly conserved amino acid sequence 604:641 a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER 604:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 2 46 theme Cell 331:334 arg1 expression 344:353 Cell surface expression 331:353 Cell surface expression of GABAARs, a prerequisite for their function, 331:400 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 0 47 theme GABAA 38:42 arg1 receptors 44:52 GABAA receptors 38:52 GABAA receptors 38:52 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 3 48 theme extracellular 654:666 arg1 subunits 702:709 the receptor subunits 689:709 the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER 689:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 3 48 theme extracellular 654:666 arg1 domain 679:684 the extracellular N-terminal domain 650:684 the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER 650:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 7 49 with interaction 1411:1421 arg1 calnexin 1428:1435 calnexin 1428:1435 calnexin 1428:1435 When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. 36244453 7 49 with interaction 1411:1421 arg1 Grp94 1493:1497 Grp94 1493:1497 Grp94 1493:1497 When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. 36244453 2 50 theme GABAARs 358:364 arg1 expression 344:353 Cell surface expression 331:353 Cell surface expression of GABAARs, a prerequisite for their function, 331:400 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 9 51 with interaction 1872:1882 arg1 calnexin 1889:1896 calnexin 1889:1896 calnexin 1889:1896 Thus, this previously uncharacterized region plays an important role in intracellular processing of GABAARs at least in part by stabilizing their interaction with calnexin. 36244453 1 52 theme pentameric 217:226 arg1 channels 253:260 pentameric GABA-gated Cl-/HCO3- ion channels 217:260 pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system 217:328 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 4 53 theme α1 847:848 arg1 subunits 862:869 the α1, β3, and γ2 subunits 843:869 the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis 843:914 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 6 54 theme ER-associated 1230:1242 arg1 degradation 1244:1254 ER-associated degradation 1230:1254 ER-associated degradation 1230:1254 However, their surface expression was increased when ER-associated degradation or proteosome function was inhibited, while modulation of ER calcium stores had little effect. 36244453 1 55 theme Cl-/HCO3- 239:247 arg1 channels 253:260 pentameric GABA-gated Cl-/HCO3- ion channels 217:260 pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system 217:328 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 9 56 from role 1790:1793 arg1 processing 1812:1821 intracellular processing 1798:1821 intracellular processing of GABAARs 1798:1832 Thus, this previously uncharacterized region plays an important role in intracellular processing of GABAARs at least in part by stabilizing their interaction with calnexin. 36244453 2 57 theme Golgi 569:573 arg1 apparatus 575:583 Golgi apparatus 569:583 Golgi apparatus 569:583 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 1 58 theme Type 148:151 arg1 GABAARs 186:192 GABAARs 186:192 GABAARs 186:192 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 1 58 theme Type 148:151 arg1 receptors 175:183 Type A γ-aminobutyric acid receptors 148:183 Type A γ-aminobutyric acid receptors (GABAARs) 148:193 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 9 59 theme GABAARs 1826:1832 arg1 processing 1812:1821 intracellular processing 1798:1821 intracellular processing of GABAARs 1798:1832 Thus, this previously uncharacterized region plays an important role in intracellular processing of GABAARs at least in part by stabilizing their interaction with calnexin. 36244453 7 60 theme decreased 1401:1409 arg1 interaction 1411:1421 decreased interaction 1401:1421 decreased interaction with calnexin 1401:1435 When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. 36244453 7 61 theme mutated 1376:1382 arg1 receptors 1384:1392 mutated receptors 1376:1392 mutated receptors 1376:1392 When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. 36244453 3 62 theme subunits 702:709 arg1 subunits 702:709 the receptor subunits 689:709 the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER 689:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 3 62 theme subunits 702:709 arg1 domain 679:684 the extracellular N-terminal domain 650:684 the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER 650:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 8 63 theme transmembrane 1676:1688 arg1 domain 1690:1695 the first transmembrane domain 1666:1695 the first transmembrane domain 1666:1695 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 1 64 theme γ-aminobutyric 155:168 arg1 GABAARs 186:192 GABAARs 186:192 GABAARs 186:192 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 1 64 theme γ-aminobutyric 155:168 arg1 receptors 175:183 Type A γ-aminobutyric acid receptors 148:183 Type A γ-aminobutyric acid receptors (GABAARs) 148:193 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 0 65 theme N-terminal 94:103 arg1 domain 119:124 the N-terminal extracellular domain 90:124 the N-terminal extracellular domain of receptor subunits 90:145 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 0 65 theme N-terminal 94:103 arg1 subunits 138:145 receptor subunits 129:145 receptor subunits 129:145 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 2 66 theme endoplasmic 538:548 arg1 ER 561:562 ER 561:562 ER 561:562 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 2 66 theme endoplasmic 538:548 arg1 reticulum 550:558 the endoplasmic reticulum 534:558 the endoplasmic reticulum (ER) 534:563 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 3 67 theme transmembrane 731:743 arg1 domain 745:750 the first transmembrane domain 721:750 the first transmembrane domain 721:750 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 0 68 theme domain 119:124 arg1 end 83:85 the end 79:85 the end of the N-terminal extracellular domain of receptor subunits 79:145 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 8 69 theme calnexin 1708:1715 arg1 binding 1717:1723 calnexin binding 1708:1723 calnexin binding 1708:1723 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 4 70 theme site-directed 890:902 arg1 mutagenesis 904:914 site-directed mutagenesis 890:914 site-directed mutagenesis 890:914 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 8 71 dep adjoining 1656:1664 arg1 domain 1690:1695 the first transmembrane domain 1666:1695 the first transmembrane domain 1666:1695 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 0 72 theme receptor 129:136 arg1 subunits 138:145 receptor subunits 129:145 receptor subunits 129:145 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 4 73 from Modifications 811:823 arg1 subunits 862:869 the α1, β3, and γ2 subunits 843:869 the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis 843:914 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 6 74 contain had 1332:1334 arg2 effect 1343:1348 little effect 1336:1348 little effect 1336:1348 However, their surface expression was increased when ER-associated degradation or proteosome function was inhibited, while modulation of ER calcium stores had little effect. 36244453 6 74 contain had 1332:1334 arg1 modulation 1300:1309 modulation 1300:1309 modulation of ER calcium stores 1300:1330 However, their surface expression was increased when ER-associated degradation or proteosome function was inhibited, while modulation of ER calcium stores had little effect. 36244453 8 75 from disruption 1588:1597 arg1 structure 1602:1610 structure 1602:1610 structure caused by mutations in the conserved region adjoining the first transmembrane domain 1602:1695 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 2 76 with assembly 434:441 arg1 chaperones 516:525 molecular chaperones 506:525 molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus 506:583 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 9 77 theme uncharacterized 1748:1762 arg1 region 1764:1769 this previously uncharacterized region 1732:1769 this previously uncharacterized region 1732:1769 Thus, this previously uncharacterized region plays an important role in intracellular processing of GABAARs at least in part by stabilizing their interaction with calnexin. 36244453 2 78 theme subunits 459:466 arg1 interactions 488:499 their transient interactions 472:499 their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus 472:583 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 2 78 theme subunits 459:466 arg1 assembly 434:441 the appropriate assembly 418:441 the appropriate assembly of the receptor subunits 418:466 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 2 79 theme molecular 506:514 arg1 chaperones 516:525 molecular chaperones 506:525 molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus 506:583 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 8 80 from mutations 1622:1630 arg1 region 1649:1654 the conserved region 1635:1654 the conserved region adjoining the first transmembrane domain 1635:1695 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 6 81 theme calcium 1317:1323 arg1 stores 1325:1330 ER calcium stores 1314:1330 ER calcium stores 1314:1330 However, their surface expression was increased when ER-associated degradation or proteosome function was inhibited, while modulation of ER calcium stores had little effect. 36244453 2 82 with interactions 488:499 arg1 chaperones 516:525 molecular chaperones 506:525 molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus 506:583 Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. 36244453 9 83 theme important 1780:1788 arg1 role 1790:1793 an important role 1777:1793 an important role in intracellular processing of GABAARs 1777:1832 Thus, this previously uncharacterized region plays an important role in intracellular processing of GABAARs at least in part by stabilizing their interaction with calnexin. 36244453 0 84 theme surface 16:22 arg1 expression 24:33 cell surface expression 11:33 cell surface expression of GABAA receptors 11:52 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 8 85 theme calnexin 1523:1530 arg1 interaction 1532:1542 calnexin interaction 1523:1542 calnexin interaction with the wt or mutated GABAAR 1523:1572 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 3 86 theme amino 623:627 arg1 sequence 634:641 a highly conserved amino acid sequence 604:641 a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER 604:808 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 1 87 theme inhibitory 276:285 arg1 transmission 287:298 inhibitory transmission 276:298 inhibitory transmission 276:298 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 4 88 theme heterologous 967:978 arg1 systems 985:991 heterologous cell systems 967:991 heterologous cell systems 967:991 Modifications of this region in the α1, β3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. 36244453 0 89 theme receptors 44:52 arg1 expression 24:33 cell surface expression 11:33 cell surface expression of GABAA receptors 11:52 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 3 90 dep subunits 702:709 arg1 adjoining 711:719 adjoining 711:719 adjoining 711:719 Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. 36244453 0 91 theme extracellular 105:117 arg1 domain 119:124 the N-terminal extracellular domain 90:124 the N-terminal extracellular domain of receptor subunits 90:145 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 0 91 theme extracellular 105:117 arg1 subunits 138:145 receptor subunits 129:145 receptor subunits 129:145 Control of cell surface expression of GABAA receptors by a conserved region at the end of the N-terminal extracellular domain of receptor subunits. 36244453 8 92 theme wt 1553:1554 arg1 GABAAR 1567:1572 the wt or mutated GABAAR 1549:1572 the wt or mutated GABAAR 1549:1572 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 1 93 theme central 307:313 arg1 system 323:328 the central nervous system 303:328 the central nervous system 303:328 Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. 36244453 7 94 theme increased 1466:1474 arg1 association 1476:1486 increased association 1466:1486 increased association with Grp94 1466:1497 When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. 36244453 8 95 theme mutated 1559:1565 arg1 GABAAR 1567:1572 the wt or mutated GABAAR 1549:1572 the wt or mutated GABAAR 1549:1572 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 36244453 9 96 theme intracellular 1798:1810 arg1 processing 1812:1821 intracellular processing 1798:1821 intracellular processing of GABAARs 1798:1832 Thus, this previously uncharacterized region plays an important role in intracellular processing of GABAARs at least in part by stabilizing their interaction with calnexin. 36244453 8 97 theme conserved 1639:1647 arg1 region 1649:1654 the conserved region 1635:1654 the conserved region adjoining the first transmembrane domain 1635:1695 Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. 35925813 7 0 theme standardized 1127:1138 arg1 Food 1154:1157 Food 1154:1157 Food 1154:1157 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 7 0 theme standardized 1127:1138 arg1 States 1147:1152 a standardized United States 1125:1152 a standardized United States Food and Drug Administration-supported BioCompute Object 1125:1209 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 7 0 theme standardized 1127:1138 arg1 Drug 1163:1166 Drug 1163:1166 Drug 1163:1166 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 10 1 theme N-glycan 1753:1760 arg1 data 1772:1775 N-glycan biomarker data 1753:1775 N-glycan biomarker data with multi-source biomedical data 1753:1809 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 8 2 from groups 1393:1398 arg1 levels 1318:1323 different levels 1308:1323 different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups 1308:1398 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 10 3 theme biomarker 1614:1622 arg1 model 1629:1633 The biomarker data model we 1610:1636 The biomarker data model we 1610:1636 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 8 4 with glycans 1295:1301 arg1 levels 1318:1323 different levels 1308:1323 different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups 1308:1398 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 9 5 theme glycomics 1461:1469 arg1 data 1471:1474 glycomics data 1461:1474 glycomics data 1461:1474 Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. 35925813 9 6 theme biomarker 1522:1530 arg1 data 1532:1535 glycan-protein biomarker data 1507:1535 glycan-protein biomarker data 1507:1535 Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. 35925813 10 7 dep model 1629:1633 arg1 we 1635:1636 we 1635:1636 we 1635:1636 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 6 8 theme liver 827:831 arg1 disease 833:839 liver disease 827:839 liver disease 827:839 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 10 9 theme multi-source 1782:1793 arg1 data 1806:1809 multi-source biomedical data 1782:1809 multi-source biomedical data 1782:1809 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 6 10 theme data 894:897 arg1 model 899:903 a cancer biomarker data model 875:903 a cancer biomarker data model 875:903 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 8 11 theme information 1274:1284 arg1 capture 1254:1260 the capture 1250:1260 the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups 1250:1398 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 5 12 theme diverse 683:689 arg1 formats 691:697 diverse formats 683:697 diverse formats 683:697 However, such data are distributed across publications and databases of diverse formats, which hamper their use in research and clinical application. 35925813 9 13 theme unified 1481:1487 arg1 framework 1489:1497 a unified framework 1479:1497 a unified framework 1479:1497 Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. 35925813 8 14 theme biomarker 1222:1230 arg1 model 1237:1241 the biomarker data model 1218:1241 the biomarker data model 1218:1241 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 5 15 theme clinical 739:746 arg1 application 748:758 clinical application 739:758 clinical application 739:758 However, such data are distributed across publications and databases of diverse formats, which hamper their use in research and clinical application. 35925813 6 16 dep integrated 846:855 arg1 panel 863:867 a panel 861:867 a panel 861:867 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 2 17 theme early 247:251 arg1 biomarkers 260:269 early cancer biomarkers 247:269 early cancer biomarkers 247:269 Great interest exists in discovering early cancer biomarkers to improve outcomes. 35925813 9 18 theme glycan-protein 1507:1520 arg1 data 1532:1535 glycan-protein biomarker data 1507:1535 glycan-protein biomarker data 1507:1535 Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. 35925813 3 19 theme data 333:336 arg1 model 338:342 a standardized data model 318:342 a standardized data model 318:342 Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. 35925813 4 20 theme altered 480:486 arg1 components 488:497 altered components 480:497 altered components in tumorigenesis 480:514 Among altered components in tumorigenesis, N-glycans exhibit substantial biomarker potential, when analyzed with their protein carriers. 35925813 8 21 theme different 1308:1316 arg1 levels 1318:1323 different levels 1308:1323 different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups 1308:1398 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 6 22 theme standard 937:944 arg1 nomenclature 946:957 standard nomenclature 937:957 standard nomenclature 937:957 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 1 23 theme biological 141:150 arg1 processes 152:160 biological processes 141:160 biological processes 141:160 Molecular biomarkers measure discrete components of biological processes that can contribute to disorders when impaired. 35925813 6 24 theme standard 1029:1036 arg1 information 1076:1086 biomarker information 1066:1086 biomarker information 1066:1086 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 6 24 theme standard 1029:1036 arg1 disease 1053:1059 disease 1053:1059 disease 1053:1059 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 6 24 theme standard 1029:1036 arg1 gene 1047:1050 gene 1047:1050 gene 1047:1050 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 6 24 theme standard 1029:1036 arg1 protein 1038:1044 standard protein 1029:1044 standard protein 1029:1044 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 0 25 theme comprehensive 53:65 arg1 model 82:86 a comprehensive biomarker data model 51:86 a comprehensive biomarker data model 51:86 Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model. 35925813 10 26 theme data 1865:1868 arg1 framework 1870:1878 a unified data framework 1855:1878 a unified data framework for glycan biomarker representation 1855:1914 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 0 27 from integration 13:23 arg1 model 82:86 a comprehensive biomarker data model 51:86 a comprehensive biomarker data model 51:86 Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model. 35925813 0 28 theme data 77:80 arg1 model 82:86 a comprehensive biomarker data model 51:86 a comprehensive biomarker data model 51:86 Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model. 35925813 0 29 from Modeling 0:7 arg1 model 82:86 a comprehensive biomarker data model 51:86 a comprehensive biomarker data model 51:86 Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model. 35925813 9 30 theme other 1588:1592 arg1 resources 1599:1607 other data resources 1588:1607 other data resources 1588:1607 Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. 35925813 10 31 theme novel 1692:1696 arg1 glycan 1698:1703 their novel glycan and glycoconjugate biomarkers 1686:1733 glycan 1698:1703 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 6 32 theme biomarker 1066:1074 arg1 protein 1038:1044 standard protein 1029:1044 standard protein 1029:1044 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 6 32 theme biomarker 1066:1074 arg1 information 1076:1086 biomarker information 1066:1086 biomarker information 1066:1086 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 10 33 dep https 1995:1999 arg1 //www.go-fair.org/fair-principles/ 2001:2034 //www.go-fair.org/fair-principles/ 2001:2034 https://www.go-fair.org/fair-principles/ 1995:2034 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 7 34 dep Food 1154:1157 arg1 Object 1204:1209 Administration-supported BioCompute Object 1168:1209 Administration-supported BioCompute Object 1168:1209 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 5 35 theme such 620:623 arg1 data 625:628 such data 620:628 such data 620:628 However, such data are distributed across publications and databases of diverse formats, which hamper their use in research and clinical application. 35925813 1 36 theme Molecular 89:97 arg1 biomarkers 99:108 Molecular biomarkers 89:108 Molecular biomarkers 89:108 Molecular biomarkers measure discrete components of biological processes that can contribute to disorders when impaired. 35925813 7 37 theme Administration-supported 1168:1191 arg1 Object 1204:1209 Administration-supported BioCompute Object 1168:1209 Administration-supported BioCompute Object 1168:1209 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 6 38 theme biomarker 884:892 arg1 model 899:903 a cancer biomarker data model 875:903 a cancer biomarker data model 875:903 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 3 39 theme biomarkers 426:435 arg1 use 413:415 use 413:415 use 413:415 Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. 35925813 3 39 theme biomarkers 426:435 arg1 understanding 395:407 understanding 395:407 understanding 395:407 Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. 35925813 0 40 theme N-glycan 28:35 arg1 biomarkers 37:46 N-glycan biomarkers 28:46 N-glycan biomarkers 28:46 Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model. 35925813 10 41 theme biomarker 1891:1899 arg1 representation 1901:1914 glycan biomarker representation 1884:1914 glycan biomarker representation 1884:1914 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 10 42 theme data 1936:1939 arg1 FAIR 1941:1944 the data FAIR 1932:1944 the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/) 1932:2035 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 5 43 theme formats 691:697 arg1 databases 670:678 databases 670:678 databases 670:678 However, such data are distributed across publications and databases of diverse formats, which hamper their use in research and clinical application. 35925813 5 43 theme formats 691:697 arg1 publications 653:664 publications 653:664 publications 653:664 However, such data are distributed across publications and databases of diverse formats, which hamper their use in research and clinical application. 35925813 6 44 theme Mass 761:764 arg1 spectrometry 766:777 Mass spectrometry 761:777 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease 761:839 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 10 45 theme biomarker 1762:1770 arg1 data 1772:1775 N-glycan biomarker data 1753:1775 N-glycan biomarker data with multi-source biomedical data 1753:1809 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 9 46 theme data 1439:1442 arg1 model 1444:1448 a standardized data model 1424:1448 a standardized data model 1424:1448 Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. 35925813 6 47 theme unique 918:923 arg1 identifier 925:934 a unique identifier 916:934 a unique identifier 916:934 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 6 48 from measures 779:786 arg1 proteins 815:822 7 serum proteins 807:822 7 serum proteins in liver disease 807:839 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 10 49 theme data 1624:1627 arg1 model 1629:1633 The biomarker data model we 1610:1636 The biomarker data model we 1610:1636 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 10 50 theme biomedical 1795:1804 arg1 data 1806:1809 multi-source biomedical data 1782:1809 multi-source biomedical data 1782:1809 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 7 51 theme Data 1089:1092 arg1 provenance 1094:1103 Data provenance 1089:1103 Data provenance 1089:1103 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 8 52 theme granular 1265:1272 arg1 information 1274:1284 granular information 1265:1284 granular information 1265:1284 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 4 53 from components 488:497 arg1 tumorigenesis 502:514 tumorigenesis 502:514 tumorigenesis 502:514 Among altered components in tumorigenesis, N-glycans exhibit substantial biomarker potential, when analyzed with their protein carriers. 35925813 6 54 theme serum 809:813 arg1 proteins 815:822 7 serum proteins 807:822 7 serum proteins in liver disease 807:839 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 6 55 theme glycan 969:974 arg1 resources 976:984 glycan resources 969:984 glycan resources 969:984 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 2 56 theme cancer 253:258 arg1 biomarkers 260:269 early cancer biomarkers 247:269 early cancer biomarkers 247:269 Great interest exists in discovering early cancer biomarkers to improve outcomes. 35925813 8 57 theme data 1232:1235 arg1 model 1237:1241 the biomarker data model 1218:1241 the biomarker data model 1218:1241 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 1 58 theme discrete 118:125 arg1 components 127:136 discrete components 118:136 discrete components of biological processes that can contribute to disorders when impaired 118:207 Molecular biomarkers measure discrete components of biological processes that can contribute to disorders when impaired. 35925813 4 59 theme biomarker 547:555 arg1 potential 557:565 substantial biomarker potential 535:565 substantial biomarker potential 535:565 Among altered components in tumorigenesis, N-glycans exhibit substantial biomarker potential, when analyzed with their protein carriers. 35925813 10 60 theme glycan 1884:1889 arg1 representation 1901:1914 glycan biomarker representation 1884:1914 glycan biomarker representation 1884:1914 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 3 61 theme standardized 320:331 arg1 model 338:342 a standardized data model 318:342 a standardized data model 318:342 Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. 35925813 0 62 theme biomarker 67:75 arg1 model 82:86 a comprehensive biomarker data model 51:86 a comprehensive biomarker data model 51:86 Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model. 35925813 1 63 theme processes 152:160 arg1 components 127:136 discrete components 118:136 discrete components of biological processes that can contribute to disorders when impaired 118:207 Molecular biomarkers measure discrete components of biological processes that can contribute to disorders when impaired. 35925813 3 64 theme multi-omics 361:371 arg1 data 373:376 multi-omics data 361:376 multi-omics data 361:376 Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. 35925813 4 65 theme substantial 535:545 arg1 potential 557:565 substantial biomarker potential 535:565 substantial biomarker potential 535:565 Among altered components in tumorigenesis, N-glycans exhibit substantial biomarker potential, when analyzed with their protein carriers. 35925813 8 66 theme abundance 1328:1336 arg1 levels 1318:1323 different levels 1308:1323 different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups 1308:1398 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 6 67 theme ontology 1005:1012 arg1 annotations 1014:1024 accession and ontology annotations 991:1024 annotations 1014:1024 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 3 68 dep understanding 395:407 arg1 the 391:393 the 391:393 the 391:393 Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. 35925813 8 69 from levels 1318:1323 arg1 groups 1393:1398 transplant groups 1382:1398 transplant groups 1382:1398 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 8 69 from levels 1318:1323 arg1 cirrhosis 1341:1349 cirrhosis 1341:1349 cirrhosis 1341:1349 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 8 69 from levels 1318:1323 arg1 carcinoma 1367:1375 hepatocellular carcinoma 1352:1375 hepatocellular carcinoma 1352:1375 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 6 70 theme accession 991:999 arg1 annotations 1014:1024 accession and ontology annotations 991:1024 annotations 1014:1024 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 8 71 theme hepatocellular 1352:1365 arg1 carcinoma 1367:1375 hepatocellular carcinoma 1352:1375 hepatocellular carcinoma 1352:1375 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 9 72 theme data 1594:1597 arg1 resources 1599:1607 other data resources 1588:1607 other data resources 1588:1607 Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. 35925813 7 73 dep States 1147:1152 arg1 Food 1154:1157 Food 1154:1157 Food 1154:1157 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 7 73 dep States 1147:1152 arg1 States 1147:1152 a standardized United States 1125:1152 a standardized United States Food and Drug Administration-supported BioCompute Object 1125:1209 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 7 73 dep States 1147:1152 arg1 Drug 1163:1166 Drug 1163:1166 Drug 1163:1166 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 7 74 theme BioCompute 1193:1202 arg1 Object 1204:1209 Administration-supported BioCompute Object 1168:1209 Administration-supported BioCompute Object 1168:1209 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 8 75 from cirrhosis 1341:1349 arg1 levels 1318:1323 different levels 1308:1323 different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups 1308:1398 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 4 76 theme protein 593:599 arg1 carriers 601:608 their protein carriers 587:608 their protein carriers 587:608 Among altered components in tumorigenesis, N-glycans exhibit substantial biomarker potential, when analyzed with their protein carriers. 35925813 8 77 theme transplant 1382:1391 arg1 groups 1393:1398 transplant groups 1382:1398 transplant groups 1382:1398 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 8 78 from abundance 1328:1336 arg1 groups 1393:1398 transplant groups 1382:1398 transplant groups 1382:1398 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 8 78 from abundance 1328:1336 arg1 cirrhosis 1341:1349 cirrhosis 1341:1349 cirrhosis 1341:1349 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 8 78 from abundance 1328:1336 arg1 carcinoma 1367:1375 hepatocellular carcinoma 1352:1375 hepatocellular carcinoma 1352:1375 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 10 79 theme unified 1857:1863 arg1 framework 1870:1878 a unified data framework 1855:1878 a unified data framework for glycan biomarker representation 1855:1914 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 6 80 from proteins 815:822 arg1 disease 833:839 liver disease 827:839 liver disease 827:839 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 10 81 theme glycoconjugate 1709:1722 arg1 biomarkers 1724:1733 their novel glycan and glycoconjugate biomarkers 1686:1733 biomarkers 1724:1733 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 0 82 theme biomarkers 37:46 arg1 integration 13:23 integration 13:23 integration 13:23 Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model. 35925813 0 82 theme biomarkers 37:46 arg1 Modeling 0:7 Modeling 0:7 Modeling 0:7 Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model. 35925813 6 83 theme cancer 877:882 arg1 model 899:903 a cancer biomarker data model 875:903 a cancer biomarker data model 875:903 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 10 84 dep Findable 1947:1954 arg1 Interoperable 1969:1981 Interoperable 1969:1981 Interoperable 1969:1981 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 10 84 dep Findable 1947:1954 arg1 Accessible 1957:1966 Accessible 1957:1966 Accessible 1957:1966 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 10 84 dep Findable 1947:1954 arg1 Reusable 1984:1991 Reusable 1984:1991 Reusable 1984:1991 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 7 85 theme United 1140:1145 arg1 Food 1154:1157 Food 1154:1157 Food 1154:1157 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 7 85 theme United 1140:1145 arg1 States 1147:1152 a standardized United States 1125:1152 a standardized United States Food and Drug Administration-supported BioCompute Object 1125:1209 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 7 85 theme United 1140:1145 arg1 Drug 1163:1166 Drug 1163:1166 Drug 1163:1166 Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. 35925813 3 86 theme novel 420:424 arg1 glycoconjugates 457:471 glycoconjugates 457:471 glycoconjugates 457:471 Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. 35925813 3 86 theme novel 420:424 arg1 biomarkers 426:435 novel biomarkers 420:435 novel biomarkers such as glycans and glycoconjugates 420:471 Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. 35925813 3 86 theme novel 420:424 arg1 glycans 445:451 glycans 445:451 glycans 445:451 Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. 35925813 6 87 theme N-glycans 794:802 arg1 measures 779:786 Mass spectrometry measures 761:786 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease 761:839 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 9 88 theme Such 1401:1404 arg1 representation 1406:1419 Such representation 1401:1419 Such representation in a standardized data model 1401:1448 Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. 35925813 9 89 from representation 1406:1419 arg1 model 1444:1448 a standardized data model 1424:1448 a standardized data model 1424:1448 Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. 35925813 2 90 theme Great 210:214 arg1 interest 216:223 Great interest 210:223 Great interest 210:223 Great interest exists in discovering early cancer biomarkers to improve outcomes. 35925813 8 91 from carcinoma 1367:1375 arg1 levels 1318:1323 different levels 1308:1323 different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups 1308:1398 Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. 35925813 10 92 with data 1772:1775 arg1 data 1806:1809 multi-source biomedical data 1782:1809 multi-source biomedical data 1782:1809 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 10 93 dep FAIR 1941:1944 arg1 https 1995:1999 https 1995:1999 https://www.go-fair.org/fair-principles/ 1995:2034 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 10 93 dep FAIR 1941:1944 arg1 Findable 1947:1954 Findable 1947:1954 Findable 1947:1954 The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/). 35925813 5 94 from use 719:721 arg1 research 726:733 research 726:733 research 726:733 However, such data are distributed across publications and databases of diverse formats, which hamper their use in research and clinical application. 35925813 5 94 from use 719:721 arg1 application 748:758 clinical application 739:758 clinical application 739:758 However, such data are distributed across publications and databases of diverse formats, which hamper their use in research and clinical application. 35925813 6 95 theme spectrometry 766:777 arg1 measures 779:786 Mass spectrometry measures 761:786 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease 761:839 Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. 35925813 9 96 theme standardized 1426:1437 arg1 model 1444:1448 a standardized data model 1424:1448 a standardized data model 1424:1448 Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. 37013685 0 0 theme hepsin 80:85 arg1 family 87:92 the hepsin family 76:92 the hepsin family 76:92 N-glycosylation mediated folding and quality control in serine proteases of the hepsin family. 37013685 0 1 from folding 25:31 arg1 proteases 63:71 serine proteases 56:71 serine proteases of the hepsin family 56:92 N-glycosylation mediated folding and quality control in serine proteases of the hepsin family. 37013685 3 2 gly glycoproteins 452:464 arg1 glycoproteins 452:464 Misfolded glycoproteins 442:464 Misfolded glycoproteins 442:464 Misfolded glycoproteins are retained in the ER by the same lectin chaperones. 37013685 8 3 theme N-glycosylation 1262:1276 arg1 sites 1278:1282 N-glycosylation sites 1262:1282 N-glycosylation sites required for protein folding and transport 1262:1325 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 7 4 theme response 1100:1107 arg1 pathways 1109:1116 stress response pathways that sense glycoprotein misfolding 1093:1151 stress response pathways that sense glycoprotein misfolding 1093:1151 This association coincides with the engagement of stress response pathways that sense glycoprotein misfolding. 37013685 2 5 dep chaperones 304:313 arg1 chaperones 304:313 the lectin chaperones calnexin and calreticulin 293:339 the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER) 293:439 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 2 5 dep chaperones 304:313 arg1 calreticulin 328:339 calreticulin 328:339 calreticulin 328:339 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 2 5 dep chaperones 304:313 arg1 calnexin 315:322 calnexin 315:322 calnexin 315:322 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 7 6 theme stress 1093:1098 arg1 pathways 1109:1116 stress response pathways that sense glycoprotein misfolding 1093:1151 stress response pathways that sense glycoprotein misfolding 1093:1151 This association coincides with the engagement of stress response pathways that sense glycoprotein misfolding. 37013685 1 7 attach attached 129:136 arg2 glycans 104:110 N-linked glycans 95:110 N-linked glycans 95:110 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 1 7 attach attached 129:136 arg1 residues 152:159 asparagine residues 141:159 asparagine residues 141:159 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 1 7 attach attached 129:136 arg3 motif 174:178 a N-X-S/T motif 164:178 a N-X-S/T motif of secretory pathway glycoproteins 164:213 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 0 8 theme family 87:92 arg1 proteases 63:71 serine proteases 56:71 serine proteases of the hepsin family 56:92 N-glycosylation mediated folding and quality control in serine proteases of the hepsin family. 37013685 4 9 theme serine 613:618 arg1 hepsin 603:608 hepsin 603:608 hepsin 603:608 The work by Sun et al. (FEBS J 2023, 10.1111/febs.16757) in this issue focusses on hepsin, a serine protease on the surface of liver and other organs. 37013685 4 9 theme serine 613:618 arg1 protease 620:627 a serine protease 611:627 a serine protease on the surface of liver and other organs 611:668 The work by Sun et al. (FEBS J 2023, 10.1111/febs.16757) in this issue focusses on hepsin, a serine protease on the surface of liver and other organs. 37013685 4 10 theme organs 663:668 arg1 surface 636:642 the surface 632:642 the surface of liver and other organs 632:668 The work by Sun et al. (FEBS J 2023, 10.1111/febs.16757) in this issue focusses on hepsin, a serine protease on the surface of liver and other organs. 37013685 7 11 theme glycoprotein 1129:1140 arg1 misfolding 1142:1151 that sense glycoprotein misfolding 1118:1151 stress response pathways that sense glycoprotein misfolding 1093:1151 This association coincides with the engagement of stress response pathways that sense glycoprotein misfolding. 37013685 5 12 theme secretory 904:912 arg1 pathway 914:920 the secretory pathway 900:920 the secretory pathway 900:920 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 5 13 theme N-glycans 718:726 arg1 positioning 703:713 spatial positioning 695:713 spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, 695:825 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 1 14 gly glycoproteins 201:213 arg1 glycoproteins 201:213 secretory pathway glycoproteins 183:213 secretory pathway glycoproteins 183:213 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 3 15 theme same 496:499 arg1 chaperones 508:517 the same lectin chaperones 492:517 the same lectin chaperones 492:517 Misfolded glycoproteins are retained in the ER by the same lectin chaperones. 37013685 2 16 theme lectin 297:302 arg1 chaperones 304:313 the lectin chaperones calnexin and calreticulin 293:339 the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER) 293:439 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 2 16 theme lectin 297:302 arg1 calreticulin 328:339 calreticulin 328:339 calreticulin 328:339 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 2 16 theme lectin 297:302 arg1 calnexin 315:322 calnexin 315:322 calnexin 315:322 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 5 17 theme calnexin 837:844 arg1 selection 846:854 calnexin selection 837:854 calnexin selection for hepsin maturation and transport 837:890 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 1 18 theme N-X-S/T 166:172 arg1 motif 174:178 a N-X-S/T motif 164:178 a N-X-S/T motif of secretory pathway glycoproteins 164:213 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 5 19 theme hepsin 765:770 arg1 hepsin 765:770 hepsin 765:770 hepsin 765:770 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 5 19 theme hepsin 765:770 arg1 domain 755:760 a conserved domain 743:760 a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, 743:825 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 0 20 from control 45:51 arg1 proteases 63:71 serine proteases 56:71 serine proteases of the hepsin family 56:92 N-glycosylation mediated folding and quality control in serine proteases of the hepsin family. 37013685 5 21 theme conserved 745:753 arg1 hepsin 765:770 hepsin 765:770 hepsin 765:770 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 5 21 theme conserved 745:753 arg1 domain 755:760 a conserved domain 743:760 a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, 743:825 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 8 22 theme lectin 1354:1359 arg1 calnexin 1371:1378 lectin chaperone calnexin 1354:1378 the lectin chaperone calnexin pathway for folding and quality control 1350:1418 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 8 23 theme N-glycosylation 1188:1202 arg1 considerations 1170:1183 The topological considerations 1154:1183 The topological considerations of N-glycosylation dissected by Sun et al. 1154:1226 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 8 24 theme key 1249:1251 arg1 sites 1253:1257 key sites 1249:1257 key sites of N-glycosylation sites required for protein folding and transport 1249:1325 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 8 24 theme key 1249:1251 arg1 sites 1278:1282 N-glycosylation sites 1262:1282 N-glycosylation sites required for protein folding and transport 1262:1325 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 2 25 theme reticulum 426:434 arg1 glycosidases 394:405 glycosidases 394:405 glycosidases 394:405 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 2 25 theme reticulum 426:434 arg1 enzymes 382:388 protein-folding enzymes 366:388 protein-folding enzymes 366:388 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 7 26 dep pathways 1109:1116 arg1 misfolding 1142:1151 that sense glycoprotein misfolding 1118:1151 stress response pathways that sense glycoprotein misfolding 1093:1151 This association coincides with the engagement of stress response pathways that sense glycoprotein misfolding. 37013685 8 27 theme chaperone 1361:1369 arg1 calnexin 1371:1378 lectin chaperone calnexin 1354:1378 the lectin chaperone calnexin pathway for folding and quality control 1350:1418 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 1 28 theme secretory 183:191 arg1 glycoproteins 201:213 secretory pathway glycoproteins 183:213 secretory pathway glycoproteins 183:213 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 8 29 theme topological 1158:1168 arg1 considerations 1170:1183 The topological considerations 1154:1183 The topological considerations of N-glycosylation dissected by Sun et al. 1154:1226 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 1 30 theme N-linked 95:102 arg1 glycans 104:110 N-linked glycans 95:110 N-linked glycans 95:110 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 8 31 theme quality 1404:1410 arg1 control 1412:1418 quality control 1404:1418 quality control 1404:1418 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 1 32 theme pathway 193:199 arg1 glycoproteins 201:213 secretory pathway glycoproteins 183:213 secretory pathway glycoproteins 183:213 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 8 33 theme calnexin 1371:1378 arg1 pathway 1380:1386 the lectin chaperone calnexin pathway 1350:1386 the lectin chaperone calnexin pathway for folding and quality control 1350:1418 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 6 34 contain has 991:993 arg1 it 971:972 it 971:972 it 971:972 If N-glycosylation is elsewhere on hepsin, then it is misfolded and has a prolonged accumulation with calnexin and BiP. 37013685 6 34 contain has 991:993 arg2 accumulation 1007:1018 a prolonged accumulation 995:1018 a prolonged accumulation with calnexin and BiP 995:1040 If N-glycosylation is elsewhere on hepsin, then it is misfolded and has a prolonged accumulation with calnexin and BiP. 37013685 5 35 theme spatial 695:701 arg1 positioning 703:713 spatial positioning 695:713 spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, 695:825 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 4 36 from protease 620:627 arg1 surface 636:642 the surface 632:642 the surface of liver and other organs 632:668 The work by Sun et al. (FEBS J 2023, 10.1111/febs.16757) in this issue focusses on hepsin, a serine protease on the surface of liver and other organs. 37013685 1 37 theme glycoproteins 201:213 arg1 motif 174:178 a N-X-S/T motif 164:178 a N-X-S/T motif of secretory pathway glycoproteins 164:213 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 3 38 theme Misfolded 442:450 arg1 glycoproteins 452:464 Misfolded glycoproteins 442:464 Misfolded glycoproteins 442:464 Misfolded glycoproteins are retained in the ER by the same lectin chaperones. 37013685 2 39 theme glycoproteins 253:265 arg1 N-glycosylation 216:230 N-glycosylation 216:230 N-glycosylation of newly synthesized glycoproteins 216:265 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 2 40 theme endoplasmic 414:424 arg1 ER 437:438 ER 437:438 ER 437:438 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 2 40 theme endoplasmic 414:424 arg1 reticulum 426:434 the endoplasmic reticulum 410:434 the endoplasmic reticulum (ER) 410:439 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 5 41 theme cysteine 810:817 arg1 domain 819:824 the scavenger receptor-rich cysteine domain 782:824 the scavenger receptor-rich cysteine domain 782:824 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 2 42 gly glycoproteins 253:265 arg1 glycoproteins 253:265 newly synthesized glycoproteins 235:265 newly synthesized glycoproteins 235:265 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 0 43 theme quality 37:43 arg1 control 45:51 quality control 37:51 quality control 37:51 N-glycosylation mediated folding and quality control in serine proteases of the hepsin family. 37013685 5 44 from positioning 703:713 arg1 side 735:738 one side 731:738 one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, 731:825 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 2 45 theme synthesized 241:251 arg1 glycoproteins 253:265 newly synthesized glycoproteins 235:265 newly synthesized glycoproteins 235:265 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 6 46 theme prolonged 997:1005 arg1 accumulation 1007:1018 a prolonged accumulation 995:1018 a prolonged accumulation with calnexin and BiP 995:1040 If N-glycosylation is elsewhere on hepsin, then it is misfolded and has a prolonged accumulation with calnexin and BiP. 37013685 0 47 theme serine 56:61 arg1 proteases 63:71 serine proteases 56:71 serine proteases of the hepsin family 56:92 N-glycosylation mediated folding and quality control in serine proteases of the hepsin family. 37013685 5 48 theme receptor-rich 796:808 arg1 domain 819:824 the scavenger receptor-rich cysteine domain 782:824 the scavenger receptor-rich cysteine domain 782:824 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 8 49 theme protein 1297:1303 arg1 folding 1305:1311 protein folding 1297:1311 protein folding 1297:1311 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 4 50 theme Sun 532:534 arg1 J 549:549 J 549:549 J 549:549 The work by Sun et al. (FEBS J 2023, 10.1111/febs.16757) in this issue focusses on hepsin, a serine protease on the surface of liver and other organs. 37013685 4 50 theme Sun 532:534 arg1 et al 536:540 Sun et al. 532:541 Sun et al. (FEBS J 2023, 10.1111/febs.16757) 532:575 The work by Sun et al. (FEBS J 2023, 10.1111/febs.16757) in this issue focusses on hepsin, a serine protease on the surface of liver and other organs. 37013685 6 51 with accumulation 1007:1018 arg1 BiP 1038:1040 BiP 1038:1040 BiP 1038:1040 If N-glycosylation is elsewhere on hepsin, then it is misfolded and has a prolonged accumulation with calnexin and BiP. 37013685 6 51 with accumulation 1007:1018 arg1 calnexin 1025:1032 calnexin 1025:1032 calnexin 1025:1032 If N-glycosylation is elsewhere on hepsin, then it is misfolded and has a prolonged accumulation with calnexin and BiP. 37013685 8 52 gly N-glycosylation 1262:1276 arg2 sites 1278:1282 N-glycosylation sites 1262:1282 N-glycosylation sites required for protein folding and transport 1262:1325 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 2 53 theme protein-folding 366:380 arg1 enzymes 382:388 protein-folding enzymes 366:388 protein-folding enzymes 366:388 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 4 54 theme liver 647:651 arg1 surface 636:642 the surface 632:642 the surface of liver and other organs 632:668 The work by Sun et al. (FEBS J 2023, 10.1111/febs.16757) in this issue focusses on hepsin, a serine protease on the surface of liver and other organs. 37013685 7 55 theme that sense 1118:1127 arg1 misfolding 1142:1151 that sense glycoprotein misfolding 1118:1151 stress response pathways that sense glycoprotein misfolding 1093:1151 This association coincides with the engagement of stress response pathways that sense glycoprotein misfolding. 37013685 7 56 gly glycoprotein 1129:1140 arg1 glycoprotein 1129:1140 that sense glycoprotein misfolding 1118:1151 stress response pathways that sense glycoprotein misfolding 1093:1151 This association coincides with the engagement of stress response pathways that sense glycoprotein misfolding. 37013685 3 57 theme lectin 501:506 arg1 chaperones 508:517 the same lectin chaperones 492:517 the same lectin chaperones 492:517 Misfolded glycoproteins are retained in the ER by the same lectin chaperones. 37013685 2 58 gly N-glycosylation 216:230 arg1 glycoproteins 253:265 newly synthesized glycoproteins 235:265 newly synthesized glycoproteins 235:265 N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). 37013685 5 59 theme hepsin 860:865 arg1 maturation 867:876 hepsin maturation 860:876 hepsin maturation 860:876 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 1 60 link N-linked 95:102 arg1 glycans 104:110 N-linked glycans 95:110 N-linked glycans 95:110 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 8 61 theme sites 1278:1282 arg1 sites 1253:1257 key sites 1249:1257 key sites of N-glycosylation sites required for protein folding and transport 1249:1325 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 8 61 theme sites 1278:1282 arg1 sites 1278:1282 N-glycosylation sites 1262:1282 N-glycosylation sites required for protein folding and transport 1262:1325 The topological considerations of N-glycosylation dissected by Sun et al. may help unravel how key sites of N-glycosylation sites required for protein folding and transport have evolved to select the lectin chaperone calnexin pathway for folding and quality control. 37013685 5 62 theme scavenger 786:794 arg1 domain 819:824 the scavenger receptor-rich cysteine domain 782:824 the scavenger receptor-rich cysteine domain 782:824 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 1 63 theme asparagine 141:150 arg1 residues 152:159 asparagine residues 141:159 asparagine residues 141:159 N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. 37013685 4 64 from work 524:527 arg1 issue 585:589 this issue 580:589 this issue 580:589 The work by Sun et al. (FEBS J 2023, 10.1111/febs.16757) in this issue focusses on hepsin, a serine protease on the surface of liver and other organs. 37013685 7 65 theme pathways 1109:1116 arg1 engagement 1079:1088 the engagement 1075:1088 the engagement of stress response pathways that sense glycoprotein misfolding 1075:1151 This association coincides with the engagement of stress response pathways that sense glycoprotein misfolding. 37013685 5 66 theme domain 755:760 arg1 side 735:738 one side 731:738 one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, 731:825 The authors deduce that spatial positioning of N-glycans on one side of a conserved domain of hepsin, known as the scavenger receptor-rich cysteine domain, regulates calnexin selection for hepsin maturation and transport through the secretory pathway. 37013685 4 67 theme other 657:661 arg1 organs 663:668 other organs 657:668 other organs 657:668 The work by Sun et al. (FEBS J 2023, 10.1111/febs.16757) in this issue focusses on hepsin, a serine protease on the surface of liver and other organs. 36866517 0 0 theme pathway 80:86 arg1 Agl29 10:14 Agl29 10:14 Agl29 10:14 Agl28 and Agl29 are key components of a Halobacterium salinarum N-glycosylation pathway. 36866517 0 0 theme pathway 80:86 arg1 components 24:33 key components 20:33 key components of a Halobacterium salinarum N-glycosylation pathway 20:86 Agl28 and Agl29 are key components of a Halobacterium salinarum N-glycosylation pathway. 36866517 0 0 theme pathway 80:86 arg1 Agl28 0:4 Agl28 0:4 Agl28 0:4 Agl28 and Agl29 are key components of a Halobacterium salinarum N-glycosylation pathway. 36866517 2 1 theme genes 488:492 arg1 genes 488:492 genes 488:492 genes demonstrated to encode N-glycosylation pathway components 488:550 In the present report, the roles of VNG1053G and VNG1054G, two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components, was considered. 36866517 2 1 theme genes 488:492 arg1 set 481:483 a set 479:483 a set of genes demonstrated to encode N-glycosylation pathway components 479:550 In the present report, the roles of VNG1053G and VNG1054G, two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components, was considered. 36866517 1 2 link N-linked 290:297 arg1 tetrasaccharide 299:313 the N-linked tetrasaccharide 286:313 the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon 286:363 Although Halobacterim salinarum provided the first example of N-glycosylation outside the eukaryotes, only recently has attention focused on delineating the pathway responsible for the assembly of the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon. 36866517 5 3 theme cell 1077:1080 arg1 growth 1082:1087 cell growth 1077:1087 cell growth 1077:1087 salinarum lacking other components of the N-glycosylation machinery, both cell growth and motility were compromised in the absence of VNG1053G or VNG1054G. 36866517 0 4 theme N-glycosylation 64:78 arg1 pathway 80:86 a Halobacterium salinarum N-glycosylation pathway 38:86 a Halobacterium salinarum N-glycosylation pathway 38:86 Agl28 and Agl29 are key components of a Halobacterium salinarum N-glycosylation pathway. 36866517 2 5 theme present 373:379 arg1 report 381:386 the present report 369:386 the present report 369:386 In the present report, the roles of VNG1053G and VNG1054G, two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components, was considered. 36866517 3 6 gly N-glycosylated 669:682 arg1 proteins 684:691 known N-glycosylated proteins 663:691 known N-glycosylated proteins 663:691 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 2 7 theme pathway 533:539 arg1 components 541:550 N-glycosylation pathway components 517:550 N-glycosylation pathway components 517:550 In the present report, the roles of VNG1053G and VNG1054G, two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components, was considered. 36866517 2 8 theme N-glycosylation 517:531 arg1 components 541:550 N-glycosylation pathway components 517:550 N-glycosylation pathway components 517:550 In the present report, the roles of VNG1053G and VNG1054G, two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components, was considered. 36866517 6 9 from roles 1190:1194 arg1 Hbt 1199:1201 Hbt 1199:1201 Hbt 1199:1201 Thus, given their demonstrated roles in Hbt. 36866517 7 10 theme pathway 1361:1367 arg1 components 1369:1378 archaeal N-glycosylation pathway components 1336:1378 archaeal N-glycosylation pathway components 1336:1378 salinarum N-glycosylation, VNG1053G and VNG1054G were re-annotated as Agl28 and Agl29, according to the nomenclature used to define archaeal N-glycosylation pathway components. 36866517 3 11 theme responsible 748:758 arg1 VNG1053G 694:701 VNG1053G 694:701 VNG1053G 694:701 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 3 11 theme responsible 748:758 arg1 glycosyltransferase 728:746 the glycosyltransferase 724:746 the glycosyltransferase responsible for addition of the linking glucose 724:794 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 5 12 theme VNG1054G 1149:1156 arg1 absence 1126:1132 the absence 1122:1132 the absence of VNG1053G or VNG1054G 1122:1156 salinarum lacking other components of the N-glycosylation machinery, both cell growth and motility were compromised in the absence of VNG1053G or VNG1054G. 36866517 3 13 theme cell 931:934 arg1 exterior 936:943 the cell exterior 927:943 the cell exterior 927:943 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 2 14 theme VNG1053G 402:409 arg1 roles 393:397 the roles 389:397 the roles of VNG1053G and VNG1054G 389:422 In the present report, the roles of VNG1053G and VNG1054G, two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components, was considered. 36866517 2 14 theme VNG1053G 402:409 arg1 proteins 429:436 two proteins 425:436 two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components 425:550 In the present report, the roles of VNG1053G and VNG1054G, two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components, was considered. 36866517 5 15 theme VNG1053G 1137:1144 arg1 absence 1126:1132 the absence 1122:1132 the absence of VNG1053G or VNG1054G 1122:1156 salinarum lacking other components of the N-glycosylation machinery, both cell growth and motility were compromised in the absence of VNG1053G or VNG1054G. 36866517 6 16 theme demonstrated 1177:1188 arg1 roles 1190:1194 their demonstrated roles 1171:1194 their demonstrated roles in Hbt 1171:1201 Thus, given their demonstrated roles in Hbt. 36866517 7 17 theme archaeal 1336:1343 arg1 components 1369:1378 archaeal N-glycosylation pathway components 1336:1378 archaeal N-glycosylation pathway components 1336:1378 salinarum N-glycosylation, VNG1053G and VNG1054G were re-annotated as Agl28 and Agl29, according to the nomenclature used to define archaeal N-glycosylation pathway components. 36866517 3 18 theme glucose 788:794 arg1 addition 764:771 addition 764:771 addition of the linking glucose 764:794 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 7 19 theme N-glycosylation 1345:1359 arg1 components 1369:1378 archaeal N-glycosylation pathway components 1336:1378 archaeal N-glycosylation pathway components 1336:1378 salinarum N-glycosylation, VNG1053G and VNG1054G were re-annotated as Agl28 and Agl29, according to the nomenclature used to define archaeal N-glycosylation pathway components. 36866517 1 20 theme N-linked 290:297 arg1 tetrasaccharide 299:313 the N-linked tetrasaccharide 286:313 the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon 286:363 Although Halobacterim salinarum provided the first example of N-glycosylation outside the eukaryotes, only recently has attention focused on delineating the pathway responsible for the assembly of the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon. 36866517 4 21 dep observed 984:991 arg1 As 981:982 As 981:982 As 981:982 As observed with Hbt. 36866517 1 22 theme Halobacterim 98:109 arg1 salinarum 111:119 Halobacterim salinarum 98:119 Halobacterim salinarum 98:119 Although Halobacterim salinarum provided the first example of N-glycosylation outside the eukaryotes, only recently has attention focused on delineating the pathway responsible for the assembly of the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon. 36866517 3 23 theme such 966:969 arg1 activity 971:978 such activity 966:978 such activity 966:978 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 1 24 theme tetrasaccharide 299:313 arg1 assembly 274:281 the assembly 270:281 the assembly of the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon 270:363 Although Halobacterim salinarum provided the first example of N-glycosylation outside the eukaryotes, only recently has attention focused on delineating the pathway responsible for the assembly of the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon. 36866517 3 25 theme N-glycosylated 669:682 arg1 proteins 684:691 known N-glycosylated proteins 663:691 known N-glycosylated proteins 663:691 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 3 26 theme linking 780:786 arg1 glucose 788:794 the linking glucose 776:794 the linking glucose 776:794 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 3 27 theme proteins 684:691 arg1 deletion 609:616 gene deletion 604:616 gene deletion 604:616 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 3 27 theme proteins 684:691 arg1 analysis 651:658 subsequent mass spectrometry analysis 622:658 subsequent mass spectrometry analysis 622:658 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 3 27 theme proteins 684:691 arg1 bioinformatics 585:598 bioinformatics 585:598 bioinformatics 585:598 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 0 28 theme key 20:22 arg1 Agl29 10:14 Agl29 10:14 Agl29 10:14 Agl28 and Agl29 are key components of a Halobacterium salinarum N-glycosylation pathway. 36866517 0 28 theme key 20:22 arg1 components 24:33 key components 20:33 key components of a Halobacterium salinarum N-glycosylation pathway 20:86 Agl28 and Agl29 are key components of a Halobacterium salinarum N-glycosylation pathway. 36866517 0 28 theme key 20:22 arg1 Agl28 0:4 Agl28 0:4 Agl28 0:4 Agl28 and Agl29 are key components of a Halobacterium salinarum N-glycosylation pathway. 36866517 1 29 theme selected 326:333 arg1 proteins 335:342 selected proteins 326:342 selected proteins 326:342 Although Halobacterim salinarum provided the first example of N-glycosylation outside the eukaryotes, only recently has attention focused on delineating the pathway responsible for the assembly of the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon. 36866517 3 30 theme lipid-bound 864:874 arg1 tetrasaccharide 876:890 the lipid-bound tetrasaccharide 860:890 the lipid-bound tetrasaccharide across the plasma membrane 860:917 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 5 31 theme N-glycosylation 1045:1059 arg1 machinery 1061:1069 the N-glycosylation machinery 1041:1069 the N-glycosylation machinery 1041:1069 salinarum lacking other components of the N-glycosylation machinery, both cell growth and motility were compromised in the absence of VNG1053G or VNG1054G. 36866517 2 32 theme VNG1054G 415:422 arg1 roles 393:397 the roles 389:397 the roles of VNG1053G and VNG1054G 389:422 In the present report, the roles of VNG1053G and VNG1054G, two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components, was considered. 36866517 2 32 theme VNG1054G 415:422 arg1 proteins 429:436 two proteins 425:436 two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components 425:550 In the present report, the roles of VNG1053G and VNG1054G, two proteins encoded by genes clustered together with a set of genes demonstrated to encode N-glycosylation pathway components, was considered. 36866517 3 33 theme known 663:667 arg1 proteins 684:691 known N-glycosylated proteins 663:691 known N-glycosylated proteins 663:691 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 5 34 theme machinery 1061:1069 arg1 components 1027:1036 other components 1021:1036 other components of the N-glycosylation machinery, both cell growth and motility 1021:1100 salinarum lacking other components of the N-glycosylation machinery, both cell growth and motility were compromised in the absence of VNG1053G or VNG1054G. 36866517 3 35 theme gene 604:607 arg1 deletion 609:616 gene deletion 604:616 gene deletion 604:616 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 3 36 dep translocates 847:858 arg1 contribute 952:961 contribute 952:961 to contribute to such activity 949:978 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 3 36 dep translocates 847:858 arg1 face 922:925 face 922:925 face 922:925 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 3 37 theme spectrometry 638:649 arg1 analysis 651:658 subsequent mass spectrometry analysis 622:658 subsequent mass spectrometry analysis 622:658 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 1 38 theme first 134:138 arg1 example 140:146 the first example 130:146 the first example of N-glycosylation outside the eukaryotes 130:188 Although Halobacterim salinarum provided the first example of N-glycosylation outside the eukaryotes, only recently has attention focused on delineating the pathway responsible for the assembly of the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon. 36866517 3 39 theme plasma 903:908 arg1 membrane 910:917 the plasma membrane 899:917 the plasma membrane 899:917 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 5 40 theme other 1021:1025 arg1 components 1027:1036 other components 1021:1036 other components of the N-glycosylation machinery, both cell growth and motility 1021:1100 salinarum lacking other components of the N-glycosylation machinery, both cell growth and motility were compromised in the absence of VNG1053G or VNG1054G. 36866517 0 41 theme salinarum 54:62 arg1 pathway 80:86 a Halobacterium salinarum N-glycosylation pathway 38:86 a Halobacterium salinarum N-glycosylation pathway 38:86 Agl28 and Agl29 are key components of a Halobacterium salinarum N-glycosylation pathway. 36866517 3 42 theme subsequent 622:631 arg1 analysis 651:658 subsequent mass spectrometry analysis 622:658 subsequent mass spectrometry analysis 622:658 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 0 43 theme Halobacterium 40:52 arg1 pathway 80:86 a Halobacterium salinarum N-glycosylation pathway 38:86 a Halobacterium salinarum N-glycosylation pathway 38:86 Agl28 and Agl29 are key components of a Halobacterium salinarum N-glycosylation pathway. 36866517 7 44 theme salinarum 1204:1212 arg1 VNG1053G 1231:1238 VNG1053G 1231:1238 VNG1053G 1231:1238 salinarum N-glycosylation, VNG1053G and VNG1054G were re-annotated as Agl28 and Agl29, according to the nomenclature used to define archaeal N-glycosylation pathway components. 36866517 7 44 theme salinarum 1204:1212 arg1 VNG1054G 1244:1251 VNG1054G 1244:1251 VNG1054G 1244:1251 salinarum N-glycosylation, VNG1053G and VNG1054G were re-annotated as Agl28 and Agl29, according to the nomenclature used to define archaeal N-glycosylation pathway components. 36866517 7 44 theme salinarum 1204:1212 arg1 Agl29 1284:1288 Agl29 1284:1288 Agl29 1284:1288 salinarum N-glycosylation, VNG1053G and VNG1054G were re-annotated as Agl28 and Agl29, according to the nomenclature used to define archaeal N-glycosylation pathway components. 36866517 7 44 theme salinarum 1204:1212 arg1 N-glycosylation 1214:1228 salinarum N-glycosylation 1204:1228 salinarum N-glycosylation 1204:1228 salinarum N-glycosylation, VNG1053G and VNG1054G were re-annotated as Agl28 and Agl29, according to the nomenclature used to define archaeal N-glycosylation pathway components. 36866517 7 44 theme salinarum 1204:1212 arg1 Agl28 1274:1278 Agl28 1274:1278 Agl28 1274:1278 salinarum N-glycosylation, VNG1053G and VNG1054G were re-annotated as Agl28 and Agl29, according to the nomenclature used to define archaeal N-glycosylation pathway components. 36866517 3 45 theme mass 633:636 arg1 analysis 651:658 subsequent mass spectrometry analysis 622:658 subsequent mass spectrometry analysis 622:658 Relying on both bioinformatics and gene deletion and subsequent mass spectrometry analysis of known N-glycosylated proteins, VNG1053G was determined to be the glycosyltransferase responsible for addition of the linking glucose, while VNG1054G was deemed to be the flippase that translocates the lipid-bound tetrasaccharide across the plasma membrane to face the cell exterior, or to contribute to such activity. 36866517 1 46 theme N-glycosylation 151:165 arg1 example 140:146 the first example 130:146 the first example of N-glycosylation outside the eukaryotes 130:188 Although Halobacterim salinarum provided the first example of N-glycosylation outside the eukaryotes, only recently has attention focused on delineating the pathway responsible for the assembly of the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon. 36866517 1 47 theme responsible 254:264 arg1 pathway 246:252 the pathway 242:252 the pathway responsible for the assembly of the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon 242:363 Although Halobacterim salinarum provided the first example of N-glycosylation outside the eukaryotes, only recently has attention focused on delineating the pathway responsible for the assembly of the N-linked tetrasaccharide decorating selected proteins in this haloarchaeon. 36585386 1 0 theme discovery 162:170 arg1 process 172:178 the drug discovery process 153:178 the drug discovery process 153:178 Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. 36585386 1 1 from Innovations 92:102 arg1 chemistry 117:125 synthetic chemistry 107:125 synthetic chemistry 107:125 Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. 36585386 5 2 theme NCI-H1975 887:895 arg1 cells 897:901 A549 and NCI-H1975 cells 878:901 cells 897:901 Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI-H1975 cells, which give us a hit for anticancer drug discovery. 36585386 4 3 used used 677:680 arg2 toolbox 555:561 This effective toolbox 540:561 This effective toolbox 540:561 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 5 4 theme A549 878:881 arg1 cells 897:901 A549 and NCI-H1975 cells 878:901 cells 897:901 Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI-H1975 cells, which give us a hit for anticancer drug discovery. 36585386 4 5 theme natural 720:726 arg1 products 728:735 natural products 720:735 natural products 720:735 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 4 6 theme convenient 574:583 arg1 route 595:599 a convenient synthetic route 572:599 a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives 572:663 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 3 7 theme natural 522:528 arg1 products 530:537 natural products 522:537 natural products 522:537 Herein, we have developed a NaClOmediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products. 36585386 2 8 theme medicinal 339:347 arg1 modules 349:355 medicinal modules 339:355 medicinal modules 339:355 As a result, it is of significance to develop novel simple and effective synthetic installation of medicinal modules to promote drug discovery. 36585386 5 9 theme biological 761:770 arg1 screening 772:780 biological screening 761:780 biological screening of the library 761:795 Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI-H1975 cells, which give us a hit for anticancer drug discovery. 36585386 5 10 theme anticancer 928:937 arg1 discovery 944:952 anticancer drug discovery 928:952 anticancer drug discovery 928:952 Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI-H1975 cells, which give us a hit for anticancer drug discovery. 36585386 3 11 theme NaClOmediated 412:424 arg1 installation 432:443 a NaClOmediated cross installation 410:443 a NaClOmediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products 410:537 Herein, we have developed a NaClOmediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products. 36585386 4 12 theme products 728:735 arg1 modification 697:708 late-stage modification 686:708 late-stage modification of drugs, natural products and peptides 686:748 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 3 13 theme cross 426:430 arg1 installation 432:443 a NaClOmediated cross installation 410:443 a NaClOmediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products 410:537 Herein, we have developed a NaClOmediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products. 36585386 0 14 theme Cross 15:19 arg1 Installation 21:32 NaClO-Mediated Cross Installation 0:32 NaClO-Mediated Cross Installation of 0:35 NaClO-Mediated Cross Installation of Indoles and Azoles Benefits Anti-cancer Hit Discovery. 36585386 2 15 theme simple 292:297 arg1 installation 323:334 novel simple and effective synthetic installation 286:334 novel simple and effective synthetic installation of medicinal modules 286:355 As a result, it is of significance to develop novel simple and effective synthetic installation of medicinal modules to promote drug discovery. 36585386 2 16 theme drug 368:371 arg1 discovery 373:381 drug discovery 368:381 drug discovery 368:381 As a result, it is of significance to develop novel simple and effective synthetic installation of medicinal modules to promote drug discovery. 36585386 0 17 theme NaClO-Mediated 0:13 arg1 Installation 21:32 NaClO-Mediated Cross Installation 0:32 NaClO-Mediated Cross Installation of 0:35 NaClO-Mediated Cross Installation of Indoles and Azoles Benefits Anti-cancer Hit Discovery. 36585386 1 18 theme synthetic 107:115 arg1 chemistry 117:125 synthetic chemistry 107:125 synthetic chemistry 107:125 Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. 36585386 5 19 theme promising 838:846 arg1 activities 859:868 promising anticancer activities 838:868 promising anticancer activities 838:868 Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI-H1975 cells, which give us a hit for anticancer drug discovery. 36585386 4 20 theme synthetic 585:593 arg1 route 595:599 a convenient synthetic route 572:599 a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives 572:663 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 4 21 theme late-stage 686:695 arg1 modification 697:708 late-stage modification 686:708 late-stage modification of drugs, natural products and peptides 686:748 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 4 22 theme drugs 713:717 arg1 modification 697:708 late-stage modification 686:708 late-stage modification of drugs, natural products and peptides 686:748 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 3 23 theme indoles 448:454 arg1 installation 432:443 a NaClOmediated cross installation 410:443 a NaClOmediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products 410:537 Herein, we have developed a NaClOmediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products. 36585386 2 24 theme novel 286:290 arg1 installation 323:334 novel simple and effective synthetic installation 286:334 novel simple and effective synthetic installation of medicinal modules 286:355 As a result, it is of significance to develop novel simple and effective synthetic installation of medicinal modules to promote drug discovery. 36585386 4 25 theme effective 545:553 arg1 toolbox 555:561 This effective toolbox 540:561 This effective toolbox 540:561 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 5 26 theme anticancer 848:857 arg1 activities 859:868 promising anticancer activities 838:868 promising anticancer activities 838:868 Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI-H1975 cells, which give us a hit for anticancer drug discovery. 36585386 2 27 theme synthetic 313:321 arg1 installation 323:334 novel simple and effective synthetic installation 286:334 novel simple and effective synthetic installation of medicinal modules 286:355 As a result, it is of significance to develop novel simple and effective synthetic installation of medicinal modules to promote drug discovery. 36585386 4 28 theme Nlinked 624:630 arg1 derivatives 653:663 Nlinked 2-(azol-1-yl) indole derivatives 624:663 Nlinked 2-(azol-1-yl) indole derivatives 624:663 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 4 29 dep Nlinked 624:630 arg1 indole 646:651 indole 646:651 indole 646:651 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 1 30 theme necessary 202:210 arg1 driver 212:217 a necessary driver 200:217 a necessary driver of drug development 200:237 Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. 36585386 5 31 theme several 815:821 arg1 adducts 823:829 several adducts 815:829 several adducts 815:829 Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI-H1975 cells, which give us a hit for anticancer drug discovery. 36585386 1 32 contain have 127:130 arg1 Innovations 92:102 Innovations 92:102 Innovations in synthetic chemistry 92:125 Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. 36585386 1 32 contain have 127:130 arg2 impact 143:148 a profound impact 132:148 a profound impact 132:148 Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. 36585386 0 33 theme Benefits Anti-cancer 56:75 arg1 Discovery 81:89 and Azoles Benefits Anti-cancer Hit Discovery 45:89 Discovery 81:89 NaClO-Mediated Cross Installation of Indoles and Azoles Benefits Anti-cancer Hit Discovery. 36585386 0 34 theme Azoles 49:54 arg1 Discovery 81:89 and Azoles Benefits Anti-cancer Hit Discovery 45:89 Discovery 81:89 NaClO-Mediated Cross Installation of Indoles and Azoles Benefits Anti-cancer Hit Discovery. 36585386 3 35 theme azoles 460:465 arg1 installation 432:443 a NaClOmediated cross installation 410:443 a NaClOmediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products 410:537 Herein, we have developed a NaClOmediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products. 36585386 1 36 theme profound 134:141 arg1 impact 143:148 a profound impact 132:148 a profound impact 132:148 Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. 36585386 4 37 link Nlinked 624:630 arg1 derivatives 653:663 Nlinked 2-(azol-1-yl) indole derivatives 624:663 Nlinked 2-(azol-1-yl) indole derivatives 624:663 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 2 38 theme effective 303:311 arg1 installation 323:334 novel simple and effective synthetic installation 286:334 novel simple and effective synthetic installation of medicinal modules 286:355 As a result, it is of significance to develop novel simple and effective synthetic installation of medicinal modules to promote drug discovery. 36585386 5 39 theme drug 939:942 arg1 discovery 944:952 anticancer drug discovery 928:952 anticancer drug discovery 928:952 Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI-H1975 cells, which give us a hit for anticancer drug discovery. 36585386 4 40 theme peptides 741:748 arg1 modification 697:708 late-stage modification 686:708 late-stage modification of drugs, natural products and peptides 686:748 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 1 41 theme drug 157:160 arg1 process 172:178 the drug discovery process 153:178 the drug discovery process 153:178 Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. 36585386 1 42 theme drug 222:225 arg1 development 227:237 drug development 222:237 drug development 222:237 Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. 36585386 5 43 theme library 789:795 arg1 screening 772:780 biological screening 761:780 biological screening of the library 761:795 Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI-H1975 cells, which give us a hit for anticancer drug discovery. 36585386 4 44 theme derivatives 653:663 arg1 library 613:619 a library 611:619 a library of Nlinked 2-(azol-1-yl) indole derivatives 611:663 This effective toolbox provides a convenient synthetic route to access a library of Nlinked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. 36585386 1 45 theme development 227:237 arg1 driver 212:217 a necessary driver 200:217 a necessary driver of drug development 200:237 Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. 36585386 0 46 theme Hit 77:79 arg1 Discovery 81:89 and Azoles Benefits Anti-cancer Hit Discovery 45:89 Discovery 81:89 NaClO-Mediated Cross Installation of Indoles and Azoles Benefits Anti-cancer Hit Discovery. 36585386 2 47 theme modules 349:355 arg1 installation 323:334 novel simple and effective synthetic installation 286:334 novel simple and effective synthetic installation of medicinal modules 286:355 As a result, it is of significance to develop novel simple and effective synthetic installation of medicinal modules to promote drug discovery. 35596004 2 0 theme endogenous 150:159 arg1 syncytin-1 189:198 syncytin-1 189:198 syncytin-1 189:198 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 0 theme endogenous 150:159 arg1 proteins 180:187 Human endogenous retrovirus-derived proteins 144:187 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 144:213 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 0 theme endogenous 150:159 arg1 syncytin-2 204:213 syncytin-2 204:213 syncytin-2 204:213 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 5 1 theme mammalian 708:716 arg1 cells 726:730 mammalian HEK293T cells 708:730 mammalian HEK293T cells 708:730 Here, we express tagged syncytin-2 in mammalian HEK293T cells and demonstrate that the tagging greatly influences the cleavage and fusogenic activity of syncytin-2. 35596004 2 2 theme Human 144:148 arg1 syncytin-1 189:198 syncytin-1 189:198 syncytin-1 189:198 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 2 theme Human 144:148 arg1 proteins 180:187 Human endogenous retrovirus-derived proteins 144:187 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 144:213 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 2 theme Human 144:148 arg1 syncytin-2 204:213 syncytin-2 204:213 syncytin-2 204:213 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 5 3 theme HEK293T 718:724 arg1 cells 726:730 mammalian HEK293T cells 708:730 mammalian HEK293T cells 708:730 Here, we express tagged syncytin-2 in mammalian HEK293T cells and demonstrate that the tagging greatly influences the cleavage and fusogenic activity of syncytin-2. 35596004 9 4 theme solid 1241:1245 arg1 foundation 1247:1256 a solid foundation 1239:1256 a solid foundation for interogating the molecular mechanisms of syncytin-2-mediated cell-cell fusion in vitro 1239:1347 These findings lay a solid foundation for interogating the molecular mechanisms of syncytin-2-mediated cell-cell fusion in vitro. 35596004 2 5 dep mediate 215:221 arg1 required 321:328 required 321:328 is required for normal placenta function and fetal development 318:379 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 4 6 theme syncytin-mediated 577:593 arg1 fusion 605:610 syncytin-mediated cell-cell fusion 577:610 syncytin-mediated cell-cell fusion 577:610 Little is currently known about the molecular mechanisms of syncytin-mediated cell-cell fusion, and their functions have not been well studied in vitro. 35596004 1 7 theme Mammalian 71:79 arg1 formation 90:98 Mammalian placenta formation 71:98 Mammalian placenta formation 71:98 Mammalian placenta formation requires continuous fusion of trophoblasts. 35596004 1 8 theme trophoblasts 130:141 arg1 fusion 120:125 continuous fusion 109:125 continuous fusion of trophoblasts 109:141 Mammalian placenta formation requires continuous fusion of trophoblasts. 35596004 5 9 theme fusogenic 801:809 arg1 activity 811:818 fusogenic activity 801:818 fusogenic activity 801:818 Here, we express tagged syncytin-2 in mammalian HEK293T cells and demonstrate that the tagging greatly influences the cleavage and fusogenic activity of syncytin-2. 35596004 1 10 theme placenta 81:88 arg1 formation 90:98 Mammalian placenta formation 71:98 Mammalian placenta formation 71:98 Mammalian placenta formation requires continuous fusion of trophoblasts. 35596004 2 11 theme placenta 341:348 arg1 function 350:357 normal placenta function 334:357 normal placenta function 334:357 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 12 from syncytiotrophoblasts 278:297 arg1 primates 302:309 primates 302:309 primates 302:309 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 3 13 theme endoprotease 432:443 arg1 furin 445:449 the endoprotease furin 428:449 the endoprotease furin 428:449 Syncytins are post-translationally cleaved by the endoprotease furin into surface (SU) and transmembrane (TM) subunits for activation. 35596004 4 14 theme molecular 553:561 arg1 mechanisms 563:572 the molecular mechanisms 549:572 the molecular mechanisms of syncytin-mediated cell-cell fusion 549:610 Little is currently known about the molecular mechanisms of syncytin-mediated cell-cell fusion, and their functions have not been well studied in vitro. 35596004 5 15 theme tagged 687:692 arg1 syncytin-2 694:703 tagged syncytin-2 687:703 tagged syncytin-2 in mammalian HEK293T cells 687:730 Here, we express tagged syncytin-2 in mammalian HEK293T cells and demonstrate that the tagging greatly influences the cleavage and fusogenic activity of syncytin-2. 35596004 7 16 theme disulfide 1003:1011 arg1 formation 1018:1026 disulfide bond formation 1003:1026 disulfide bond formation 1003:1026 Furthermore, when N-linked glycosylation and disulfide bond formation are blocked, the cleavage and fusogenic activity of syncytin-2 are inhibited. 35596004 2 17 theme normal 334:339 arg1 function 350:357 normal placenta function 334:357 normal placenta function 334:357 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 9 18 theme fusion 1333:1338 arg1 mechanisms 1289:1298 the molecular mechanisms 1275:1298 the molecular mechanisms of syncytin-2-mediated cell-cell fusion 1275:1338 These findings lay a solid foundation for interogating the molecular mechanisms of syncytin-2-mediated cell-cell fusion in vitro. 35596004 6 19 theme tagged 863:868 arg1 SU 870:871 the N-terminal tagged SU 848:871 the N-terminal tagged SU 848:871 By detecting the N-terminal tagged SU, we find that it is released into the extracellular space during the fusion process. 35596004 1 20 theme continuous 109:118 arg1 fusion 120:125 continuous fusion 109:125 continuous fusion of trophoblasts 109:141 Mammalian placenta formation requires continuous fusion of trophoblasts. 35596004 4 21 theme cell-cell 595:603 arg1 fusion 605:610 syncytin-mediated cell-cell fusion 577:610 syncytin-mediated cell-cell fusion 577:610 Little is currently known about the molecular mechanisms of syncytin-mediated cell-cell fusion, and their functions have not been well studied in vitro. 35596004 5 22 from syncytin-2 694:703 arg1 cells 726:730 mammalian HEK293T cells 708:730 mammalian HEK293T cells 708:730 Here, we express tagged syncytin-2 in mammalian HEK293T cells and demonstrate that the tagging greatly influences the cleavage and fusogenic activity of syncytin-2. 35596004 7 23 link N-linked 976:983 arg1 glycosylation 985:997 N-linked glycosylation 976:997 N-linked glycosylation 976:997 Furthermore, when N-linked glycosylation and disulfide bond formation are blocked, the cleavage and fusogenic activity of syncytin-2 are inhibited. 35596004 6 24 theme N-terminal 852:861 arg1 SU 870:871 the N-terminal tagged SU 848:871 the N-terminal tagged SU 848:871 By detecting the N-terminal tagged SU, we find that it is released into the extracellular space during the fusion process. 35596004 0 25 theme Human 35:39 arg1 Syncytin-2 59:68 Fusion-Competent Human Placental Fusogen Syncytin-2 18:68 Fusion-Competent Human Placental Fusogen Syncytin-2 18:68 Reconstitution of Fusion-Competent Human Placental Fusogen Syncytin-2. 35596004 2 26 dep proteins 180:187 arg1 syncytin-1 189:198 syncytin-1 189:198 syncytin-1 189:198 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 26 dep proteins 180:187 arg1 proteins 180:187 Human endogenous retrovirus-derived proteins 144:187 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 144:213 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 26 dep proteins 180:187 arg1 syncytin-2 204:213 syncytin-2 204:213 syncytin-2 204:213 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 8 27 theme functional 1138:1147 arg1 syncytin-2 1149:1158 functional syncytin-2 1138:1158 functional syncytin-2 1138:1158 Finally, we were able to purify functional syncytin-2 from HEK293T cells and incorporate it into proteoliposomes. 35596004 7 28 dep cleavage 1045:1052 arg1 the 1041:1043 the 1041:1043 the 1041:1043 Furthermore, when N-linked glycosylation and disulfide bond formation are blocked, the cleavage and fusogenic activity of syncytin-2 are inhibited. 35596004 0 29 theme Fusion-Competent 18:33 arg1 Syncytin-2 59:68 Fusion-Competent Human Placental Fusogen Syncytin-2 18:68 Fusion-Competent Human Placental Fusogen Syncytin-2 18:68 Reconstitution of Fusion-Competent Human Placental Fusogen Syncytin-2. 35596004 9 30 theme syncytin-2-mediated 1303:1321 arg1 fusion 1333:1338 syncytin-2-mediated cell-cell fusion 1303:1338 syncytin-2-mediated cell-cell fusion 1303:1338 These findings lay a solid foundation for interogating the molecular mechanisms of syncytin-2-mediated cell-cell fusion in vitro. 35596004 2 31 theme fetal 363:367 arg1 development 369:379 fetal development 363:379 fetal development 363:379 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 0 32 theme Fusogen 51:57 arg1 Syncytin-2 59:68 Fusion-Competent Human Placental Fusogen Syncytin-2 18:68 Fusion-Competent Human Placental Fusogen Syncytin-2 18:68 Reconstitution of Fusion-Competent Human Placental Fusogen Syncytin-2. 35596004 9 33 theme cell-cell 1323:1331 arg1 fusion 1333:1338 syncytin-2-mediated cell-cell fusion 1303:1338 syncytin-2-mediated cell-cell fusion 1303:1338 These findings lay a solid foundation for interogating the molecular mechanisms of syncytin-2-mediated cell-cell fusion in vitro. 35596004 0 34 theme Placental 41:49 arg1 Syncytin-2 59:68 Fusion-Competent Human Placental Fusogen Syncytin-2 18:68 Fusion-Competent Human Placental Fusogen Syncytin-2 18:68 Reconstitution of Fusion-Competent Human Placental Fusogen Syncytin-2. 35596004 2 35 theme cell-cell 223:231 arg1 fusion 233:238 cell-cell fusion 223:238 cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates 223:309 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 7 36 theme syncytin-2 1080:1089 arg1 cleavage 1045:1052 cleavage 1045:1052 cleavage 1045:1052 Furthermore, when N-linked glycosylation and disulfide bond formation are blocked, the cleavage and fusogenic activity of syncytin-2 are inhibited. 35596004 7 36 theme syncytin-2 1080:1089 arg1 activity 1068:1075 fusogenic activity 1058:1075 fusogenic activity 1058:1075 Furthermore, when N-linked glycosylation and disulfide bond formation are blocked, the cleavage and fusogenic activity of syncytin-2 are inhibited. 35596004 4 37 theme fusion 605:610 arg1 mechanisms 563:572 the molecular mechanisms 549:572 the molecular mechanisms of syncytin-mediated cell-cell fusion 549:610 Little is currently known about the molecular mechanisms of syncytin-mediated cell-cell fusion, and their functions have not been well studied in vitro. 35596004 6 38 theme fusion 942:947 arg1 process 949:955 the fusion process 938:955 the fusion process 938:955 By detecting the N-terminal tagged SU, we find that it is released into the extracellular space during the fusion process. 35596004 0 39 theme Syncytin-2 59:68 arg1 Reconstitution 0:13 Reconstitution 0:13 Reconstitution of Fusion-Competent Human Placental Fusogen Syncytin-2 0:68 Reconstitution of Fusion-Competent Human Placental Fusogen Syncytin-2. 35596004 8 40 theme HEK293T 1165:1171 arg1 cells 1173:1177 HEK293T cells 1165:1177 HEK293T cells 1165:1177 Finally, we were able to purify functional syncytin-2 from HEK293T cells and incorporate it into proteoliposomes. 35596004 6 41 theme extracellular 911:923 arg1 space 925:929 the extracellular space 907:929 the extracellular space 907:929 By detecting the N-terminal tagged SU, we find that it is released into the extracellular space during the fusion process. 35596004 2 42 link retrovirus-derived 161:178 arg1 syncytin-1 189:198 syncytin-1 189:198 syncytin-1 189:198 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 42 link retrovirus-derived 161:178 arg1 proteins 180:187 Human endogenous retrovirus-derived proteins 144:187 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 144:213 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 42 link retrovirus-derived 161:178 arg1 syncytin-2 204:213 syncytin-2 204:213 syncytin-2 204:213 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 7 43 theme N-linked 976:983 arg1 glycosylation 985:997 N-linked glycosylation 976:997 N-linked glycosylation 976:997 Furthermore, when N-linked glycosylation and disulfide bond formation are blocked, the cleavage and fusogenic activity of syncytin-2 are inhibited. 35596004 2 44 theme cytotrophoblasts 253:268 arg1 fusion 233:238 cell-cell fusion 223:238 cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates 223:309 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 7 45 theme bond 1013:1016 arg1 formation 1018:1026 disulfide bond formation 1003:1026 disulfide bond formation 1003:1026 Furthermore, when N-linked glycosylation and disulfide bond formation are blocked, the cleavage and fusogenic activity of syncytin-2 are inhibited. 35596004 5 46 theme syncytin-2 823:832 arg1 activity 811:818 fusogenic activity 801:818 fusogenic activity 801:818 Here, we express tagged syncytin-2 in mammalian HEK293T cells and demonstrate that the tagging greatly influences the cleavage and fusogenic activity of syncytin-2. 35596004 5 46 theme syncytin-2 823:832 arg1 cleavage 788:795 cleavage 788:795 cleavage 788:795 Here, we express tagged syncytin-2 in mammalian HEK293T cells and demonstrate that the tagging greatly influences the cleavage and fusogenic activity of syncytin-2. 35596004 2 47 theme placental 243:251 arg1 cytotrophoblasts 253:268 placental cytotrophoblasts 243:268 placental cytotrophoblasts 243:268 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 7 48 theme fusogenic 1058:1066 arg1 activity 1068:1075 fusogenic activity 1058:1075 fusogenic activity 1058:1075 Furthermore, when N-linked glycosylation and disulfide bond formation are blocked, the cleavage and fusogenic activity of syncytin-2 are inhibited. 35596004 3 49 theme transmembrane 473:485 arg1 subunits 492:499 surface (SU) and transmembrane (TM) subunits 456:499 subunits 492:499 Syncytins are post-translationally cleaved by the endoprotease furin into surface (SU) and transmembrane (TM) subunits for activation. 35596004 3 49 theme transmembrane 473:485 arg1 TM 488:489 TM 488:489 TM 488:489 Syncytins are post-translationally cleaved by the endoprotease furin into surface (SU) and transmembrane (TM) subunits for activation. 35596004 9 50 theme molecular 1279:1287 arg1 mechanisms 1289:1298 the molecular mechanisms 1275:1298 the molecular mechanisms of syncytin-2-mediated cell-cell fusion 1275:1338 These findings lay a solid foundation for interogating the molecular mechanisms of syncytin-2-mediated cell-cell fusion in vitro. 35596004 5 51 dep cleavage 788:795 arg1 the 784:786 the 784:786 the 784:786 Here, we express tagged syncytin-2 in mammalian HEK293T cells and demonstrate that the tagging greatly influences the cleavage and fusogenic activity of syncytin-2. 35596004 2 52 theme retrovirus-derived 161:178 arg1 syncytin-1 189:198 syncytin-1 189:198 syncytin-1 189:198 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 52 theme retrovirus-derived 161:178 arg1 proteins 180:187 Human endogenous retrovirus-derived proteins 144:187 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 144:213 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35596004 2 52 theme retrovirus-derived 161:178 arg1 syncytin-2 204:213 syncytin-2 204:213 syncytin-2 204:213 Human endogenous retrovirus-derived proteins syncytin-1 and syncytin-2 mediate cell-cell fusion of placental cytotrophoblasts to form syncytiotrophoblasts in primates, which is required for normal placenta function and fetal development. 35628619 1 0 from phenotypes 225:234 arg1 knockouts 243:251 the knockouts 239:251 the knockouts of the same gene by different approaches 239:292 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 3 1 theme weak 799:802 arg1 alleles 804:810 weak alleles 799:810 weak alleles 799:810 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 0 2 theme Degradation 82:92 arg1 Regulation 35:44 the Regulation 31:44 the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) 31:99 The Role of SBI2/ALG12/EBS4 in the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) Studied by a Null Allele. 35628619 0 3 from Role 4:7 arg1 Regulation 35:44 the Regulation 31:44 the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) 31:99 The Role of SBI2/ALG12/EBS4 in the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) Studied by a Null Allele. 35628619 3 4 theme demanding 840:848 arg1 investigations 858:871 demanding further investigations 840:871 demanding further investigations 840:871 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 2 5 theme endoplasmic 506:516 arg1 ERAD 552:555 ERAD 552:555 ERAD 552:555 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 2 5 theme endoplasmic 506:516 arg1 degradation 539:549 endoplasmic reticulum-associated degradation 506:549 endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) 506:592 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 3 6 theme further 850:856 arg1 investigations 858:871 demanding further investigations 840:871 demanding further investigations 840:871 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 9 7 theme multiple 1524:1531 arg1 approaches 1533:1542 multiple approaches 1524:1542 multiple approaches 1524:1542 Further, our study advocates the necessity and importance of using multiple approaches to validate genetics study. 35628619 7 8 contain had 1240:1242 arg2 sensitivity 1251:1261 higher sensitivity 1244:1261 higher sensitivity to tunicamycin and salt 1244:1285 Moreover, concomitant with impaired and misfolded proteins accumulated in the ER, sbi2 had higher sensitivity to tunicamycin and salt than the wild-type. 35628619 7 8 contain had 1240:1242 arg1 sbi2 1235:1238 sbi2 1235:1238 sbi2 1235:1238 Moreover, concomitant with impaired and misfolded proteins accumulated in the ER, sbi2 had higher sensitivity to tunicamycin and salt than the wild-type. 35628619 5 9 dep mutants 1018:1024 arg1 bri1-5 1026:1031 bri1-5 1026:1031 bri1-5 1026:1031 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 5 9 dep mutants 1018:1024 arg1 mutants 1018:1024 brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 993:1053 brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 993:1074 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 5 9 dep mutants 1018:1024 arg1 bri1-9 1034:1039 bri1-9 1034:1039 bri1-9 1034:1039 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 5 9 dep mutants 1018:1024 arg1 bri1-235 1046:1053 bri1-235 1046:1053 bri1-235 1046:1053 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 2 10 theme proteins 493:500 arg1 ERAD 552:555 ERAD 552:555 ERAD 552:555 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 2 10 theme proteins 493:500 arg1 transfer 464:471 the transfer 460:471 the transfer of correctly folded proteins 460:500 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 2 10 theme proteins 493:500 arg1 degradation 539:549 endoplasmic reticulum-associated degradation 506:549 endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) 506:592 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 5 11 theme ER-trapped 1060:1069 arg1 BRI1 1071:1074 ER-trapped BRI1 1060:1074 ER-trapped BRI1 1060:1074 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 2 12 theme α 600:600 arg1 6-mannosyltransferase 605:625 an α 1, 6-mannosyltransferase 597:625 6-mannosyltransferase 605:625 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 2 12 theme α 600:600 arg1 complex 364:370 complex 364:370 complex 364:370 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 2 12 theme α 600:600 arg1 cotranslational 387:401 cotranslational 387:401 cotranslational 387:401 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 8 13 gly glycoproteins 1404:1416 arg1 glycoproteins 1404:1416 misfolded glycoproteins 1394:1416 misfolded glycoproteins 1394:1416 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 2 14 theme folded 486:491 arg1 proteins 493:500 correctly folded proteins 476:500 correctly folded proteins 476:500 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 3 15 theme T-DNA 686:690 arg1 alg12-T 701:707 T-DNA knockout alg12-T 686:707 T-DNA knockout alg12-T 686:707 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 4 16 from mutation 936:943 arg1 ALG12/EBS4 948:957 ALG12/EBS4 948:957 ALG12/EBS4 948:957 Here, we isolated a true null allele, sbi2, with the W258Stop mutation in ALG12/EBS4. 35628619 1 17 theme long-standing 157:169 arg1 problem 171:177 a long-standing problem 155:177 a long-standing problem in genetics 155:189 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 1 17 theme long-standing 157:169 arg1 lethality 142:150 lethality 142:150 lethality 142:150 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 1 17 theme long-standing 157:169 arg1 Redundancy 127:136 Redundancy 127:136 Redundancy 127:136 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 2 18 theme post-translational 407:424 arg1 modification 434:445 ubiquitous cotranslational and post-translational protein modification 376:445 modification 434:445 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 3 19 theme knockout 692:699 arg1 alg12-T 701:707 T-DNA knockout alg12-T 686:707 T-DNA knockout alg12-T 686:707 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 7 20 theme misfolded 1193:1201 arg1 proteins 1203:1210 misfolded proteins 1193:1210 misfolded proteins 1193:1210 Moreover, concomitant with impaired and misfolded proteins accumulated in the ER, sbi2 had higher sensitivity to tunicamycin and salt than the wild-type. 35628619 3 21 theme likely 725:730 arg1 mutants 742:748 likely ebs4 null mutants 725:748 likely ebs4 null mutants isolated by forward genetics 725:777 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 8 22 from role 1337:1340 arg1 regulation 1368:1377 the regulation 1364:1377 the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response 1364:1454 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 5 23 with mutants 1018:1024 arg1 BRI1 1071:1074 ER-trapped BRI1 1060:1074 ER-trapped BRI1 1060:1074 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 1 24 theme same 260:263 arg1 gene 265:268 the same gene 256:268 the same gene 256:268 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 8 25 theme stress 1440:1445 arg1 response 1447:1454 stress response 1440:1454 stress response 1440:1454 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 3 26 from lethal 712:717 arg1 Arabidopsis 673:683 Arabidopsis 673:683 Arabidopsis 673:683 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 0 27 theme SBI2/ALG12/EBS4 12:26 arg1 Role 4:7 The Role 0:7 The Role of SBI2/ALG12/EBS4 in the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) 0:99 The Role of SBI2/ALG12/EBS4 in the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) Studied by a Null Allele. 35628619 1 28 theme gene 265:268 arg1 knockouts 243:251 the knockouts 239:251 the knockouts of the same gene by different approaches 239:292 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 0 29 theme Null 114:117 arg1 Allele 119:124 a Null Allele 112:124 a Null Allele 112:124 The Role of SBI2/ALG12/EBS4 in the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) Studied by a Null Allele. 35628619 5 30 theme brassinosteroid 993:1007 arg1 bri1-5 1026:1031 bri1-5 1026:1031 bri1-5 1026:1031 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 5 30 theme brassinosteroid 993:1007 arg1 mutants 1018:1024 brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 993:1053 brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 993:1074 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 5 30 theme brassinosteroid 993:1007 arg1 bri1-9 1034:1039 bri1-9 1034:1039 bri1-9 1034:1039 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 5 30 theme brassinosteroid 993:1007 arg1 bri1-235 1046:1053 bri1-235 1046:1053 bri1-235 1046:1053 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 8 31 theme SBI2/ALG12/EBS4 1345:1359 arg1 role 1337:1340 the role 1333:1340 the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response 1333:1454 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 9 32 theme genetics 1556:1563 arg1 study 1565:1569 genetics study 1556:1569 genetics study 1556:1569 Further, our study advocates the necessity and importance of using multiple approaches to validate genetics study. 35628619 9 33 dep necessity 1490:1498 arg1 the 1486:1488 the 1486:1488 the 1486:1488 Further, our study advocates the necessity and importance of using multiple approaches to validate genetics study. 35628619 4 34 theme null 899:902 arg1 sbi2 912:915 sbi2 912:915 sbi2 912:915 Here, we isolated a true null allele, sbi2, with the W258Stop mutation in ALG12/EBS4. 35628619 4 34 theme null 899:902 arg1 allele 904:909 a true null allele 892:909 a true null allele 892:909 Here, we isolated a true null allele, sbi2, with the W258Stop mutation in ALG12/EBS4. 35628619 4 35 theme W258Stop 927:934 arg1 mutation 936:943 the W258Stop mutation 923:943 the W258Stop mutation in ALG12/EBS4 923:957 Here, we isolated a true null allele, sbi2, with the W258Stop mutation in ALG12/EBS4. 35628619 1 36 theme different 273:281 arg1 approaches 283:292 different approaches 273:292 different approaches 273:292 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 8 37 theme glycoproteins 1404:1416 arg1 ERAD 1386:1389 the ERAD 1382:1389 the ERAD of misfolded glycoproteins 1382:1416 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 8 37 theme glycoproteins 1404:1416 arg1 plant 1423:1427 plant growth and stress response 1423:1454 plant growth and stress response 1423:1454 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 1 38 dep problem 171:177 arg1 drives 294:299 drives 294:299 drives this problem to a new high 294:326 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 3 39 theme perplexing 813:822 arg1 researchers 824:834 perplexing researchers 813:834 perplexing researchers 813:834 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 3 40 theme ebs4 732:735 arg1 mutants 742:748 likely ebs4 null mutants 725:748 likely ebs4 null mutants isolated by forward genetics 725:777 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 8 41 dep plant 1423:1427 arg1 growth 1429:1434 growth 1429:1434 growth 1429:1434 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 8 41 dep plant 1423:1427 arg1 response 1447:1454 stress response 1440:1454 stress response 1440:1454 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 2 42 theme reticulum-associated 518:537 arg1 ERAD 552:555 ERAD 552:555 ERAD 552:555 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 2 42 theme reticulum-associated 518:537 arg1 degradation 539:549 endoplasmic reticulum-associated degradation 506:549 endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) 506:592 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 8 43 theme plant 1423:1427 arg1 regulation 1368:1377 the regulation 1364:1377 the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response 1364:1454 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 1 44 theme minimal 206:212 arg1 phenotypes 225:234 minimal and lethal phenotypes 206:234 minimal and lethal phenotypes in the knockouts of the same gene by different approaches 206:292 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 3 45 from Arabidopsis 673:683 arg1 lethal 712:717 lethal 712:717 lethal 712:717 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 2 46 theme proteins 571:578 arg1 ERAD 552:555 ERAD 552:555 ERAD 552:555 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 2 46 theme proteins 571:578 arg1 transfer 464:471 the transfer 460:471 the transfer of correctly folded proteins 460:500 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 2 46 theme proteins 571:578 arg1 degradation 539:549 endoplasmic reticulum-associated degradation 506:549 endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) 506:592 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 2 47 link -linked 339:345 arg1 glycosylation 347:359 Asn (N)-linked glycosylation 332:359 Asn (N)-linked glycosylation 332:359 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 7 48 theme higher 1244:1249 arg1 sensitivity 1251:1261 higher sensitivity 1244:1261 higher sensitivity to tunicamycin and salt 1244:1285 Moreover, concomitant with impaired and misfolded proteins accumulated in the ER, sbi2 had higher sensitivity to tunicamycin and salt than the wild-type. 35628619 2 49 theme protein 426:432 arg1 modification 434:445 ubiquitous cotranslational and post-translational protein modification 376:445 modification 434:445 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 3 50 theme null 737:740 arg1 mutants 742:748 likely ebs4 null mutants 725:748 likely ebs4 null mutants isolated by forward genetics 725:777 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 2 51 theme misfolded 561:569 arg1 ALG12 581:585 ALG12 581:585 ALG12 (EBS4) 581:592 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 2 51 theme misfolded 561:569 arg1 proteins 571:578 misfolded proteins 561:578 misfolded proteins 561:578 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 5 52 theme receptor 1009:1016 arg1 bri1-5 1026:1031 bri1-5 1026:1031 bri1-5 1026:1031 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 5 52 theme receptor 1009:1016 arg1 mutants 1018:1024 brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 993:1053 brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 993:1074 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 5 52 theme receptor 1009:1016 arg1 bri1-9 1034:1039 bri1-9 1034:1039 bri1-9 1034:1039 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 5 52 theme receptor 1009:1016 arg1 bri1-235 1046:1053 bri1-235 1046:1053 bri1-235 1046:1053 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 2 53 dep complex 364:370 arg1 a 362:362 a 362:362 a 362:362 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 5 54 theme mutants 1018:1024 arg1 sensitivity 978:988 the sensitivity 974:988 the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids 974:1094 sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. 35628619 8 55 theme ERAD 1386:1389 arg1 regulation 1368:1377 the regulation 1364:1377 the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response 1364:1454 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 1 56 from problem 171:177 arg1 genetics 182:189 genetics 182:189 genetics 182:189 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 2 57 from 6-mannosyltransferase 605:625 arg1 glycosylation 347:359 Asn (N)-linked glycosylation 332:359 Asn (N)-linked glycosylation 332:359 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 1 58 theme lethal 218:223 arg1 phenotypes 225:234 minimal and lethal phenotypes 206:234 minimal and lethal phenotypes in the knockouts of the same gene by different approaches 206:292 Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. 35628619 0 59 theme Reticulum-Associated 61:80 arg1 Degradation 82:92 Endoplasmic Reticulum-Associated Degradation 49:92 Endoplasmic Reticulum-Associated Degradation (ERAD) 49:99 The Role of SBI2/ALG12/EBS4 in the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) Studied by a Null Allele. 35628619 0 59 theme Reticulum-Associated 61:80 arg1 ERAD 95:98 ERAD 95:98 ERAD 95:98 The Role of SBI2/ALG12/EBS4 in the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) Studied by a Null Allele. 35628619 4 60 theme true 894:897 arg1 sbi2 912:915 sbi2 912:915 sbi2 912:915 Here, we isolated a true null allele, sbi2, with the W258Stop mutation in ALG12/EBS4. 35628619 4 60 theme true 894:897 arg1 allele 904:909 a true null allele 892:909 a true null allele 892:909 Here, we isolated a true null allele, sbi2, with the W258Stop mutation in ALG12/EBS4. 35628619 8 61 theme misfolded 1394:1402 arg1 glycoproteins 1404:1416 misfolded glycoproteins 1394:1416 misfolded glycoproteins 1394:1416 Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. 35628619 2 62 theme -linked 339:345 arg1 glycosylation 347:359 Asn (N)-linked glycosylation 332:359 Asn (N)-linked glycosylation 332:359 In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. 35628619 3 63 theme forward 762:768 arg1 genetics 770:777 forward genetics 762:777 forward genetics 762:777 In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. 35628619 0 64 theme Endoplasmic 49:59 arg1 Degradation 82:92 Endoplasmic Reticulum-Associated Degradation 49:92 Endoplasmic Reticulum-Associated Degradation (ERAD) 49:99 The Role of SBI2/ALG12/EBS4 in the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) Studied by a Null Allele. 35628619 0 64 theme Endoplasmic 49:59 arg1 ERAD 95:98 ERAD 95:98 ERAD 95:98 The Role of SBI2/ALG12/EBS4 in the Regulation of Endoplasmic Reticulum-Associated Degradation (ERAD) Studied by a Null Allele. 37169147 7 0 theme old 1098:1100 arg1 drug 1102:1105 an old drug 1095:1105 an old drug in the future treatment of shift work and circadian misalignment 1095:1170 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 7 1 theme novel 974:978 arg1 mechanism 990:998 a novel molecular mechanism 972:998 a novel molecular mechanism of GlcN in regulating clock phase 972:1032 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 2 2 theme clock 385:389 arg1 proteins 391:398 clock proteins 385:398 clock proteins 385:398 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 0 3 theme AMPK/mTOR 83:91 arg1 pathway 93:99 AMPK/mTOR pathway 83:99 AMPK/mTOR pathway 83:99 d-Glucosamine induces circadian phase delay by promoting BMAL1 degradation through AMPK/mTOR pathway. 37169147 1 4 theme circadian 172:180 arg1 regulation 191:200 circadian feedback regulation 172:200 circadian feedback regulation 172:200 Circadian rhythms are closely linked to the metabolic network through circadian feedback regulation. 37169147 7 5 theme new 1083:1085 arg1 use 1087:1089 new use 1083:1089 new use for an old drug in the future treatment of shift work and circadian misalignment 1083:1170 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 5 6 theme p-AMPK 735:740 arg1 activity 742:749 p-AMPK activity 735:749 p-AMPK activity 735:749 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 3 7 dep found 410:414 arg1 out 416:418 out 416:418 out 416:418 Here, we found out that, among the downstream metabolites regulated by d-glucosamine (GlcN) in HBP salvage pathway, only GlcN is able to induce circadian phase delay both in vitro and in vivo. 37169147 2 8 theme circadian 292:300 arg1 rhythms 302:308 circadian rhythms 292:308 circadian rhythms 292:308 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 5 9 theme human 849:853 arg1 line 860:863 human cell line 849:863 human cell line 849:863 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 4 10 theme O-GlcNAcylation 679:693 arg1 independent 664:674 independent 664:674 independent 664:674 Mechanistic studies indicated that the phase-shift induced by GlcN is independent of O-GlcNAcylation. 37169147 4 10 theme O-GlcNAcylation 679:693 arg1 phase-shift 633:643 the phase-shift 629:643 the phase-shift induced by GlcN 629:659 Mechanistic studies indicated that the phase-shift induced by GlcN is independent of O-GlcNAcylation. 37169147 7 11 theme shift 1134:1138 arg1 work 1140:1143 shift work 1134:1143 shift work 1134:1143 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 5 12 theme p-BMAL1 833:839 arg1 down-regulation 814:828 down-regulation 814:828 down-regulation of p-BMAL1 both in human cell line and mouse tissues 814:881 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 1 13 theme feedback 182:189 arg1 regulation 191:200 circadian feedback regulation 172:200 circadian feedback regulation 172:200 Circadian rhythms are closely linked to the metabolic network through circadian feedback regulation. 37169147 7 14 theme misalignment 1159:1170 arg1 treatment 1121:1129 the future treatment 1110:1129 the future treatment of shift work and circadian misalignment 1110:1170 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 5 15 theme cell 855:858 arg1 line 860:863 human cell line 849:863 human cell line 849:863 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 7 16 theme work 1140:1143 arg1 treatment 1121:1129 the future treatment 1110:1129 the future treatment of shift work and circadian misalignment 1110:1170 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 7 17 theme GlcN 1075:1078 arg1 potential 1062:1070 the therapeutic potential 1046:1070 the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment 1046:1170 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 2 18 theme O-linked 322:329 arg1 O-GlcNAcylation 365:379 O-GlcNAcylation 365:379 O-GlcNAcylation 365:379 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 2 18 theme O-linked 322:329 arg1 N-acetylglucosamine 331:349 the O-linked N-acetylglucosamine 318:349 the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins 318:398 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 3 19 theme downstream 436:445 arg1 metabolites 447:457 the downstream metabolites 432:457 the downstream metabolites regulated by d-glucosamine (GlcN) in HBP salvage pathway 432:514 Here, we found out that, among the downstream metabolites regulated by d-glucosamine (GlcN) in HBP salvage pathway, only GlcN is able to induce circadian phase delay both in vitro and in vivo. 37169147 0 20 theme phase 32:36 arg1 delay 38:42 circadian phase delay 22:42 circadian phase delay 22:42 d-Glucosamine induces circadian phase delay by promoting BMAL1 degradation through AMPK/mTOR pathway. 37169147 3 21 theme circadian 545:553 arg1 delay 561:565 circadian phase delay 545:565 circadian phase delay 545:565 Here, we found out that, among the downstream metabolites regulated by d-glucosamine (GlcN) in HBP salvage pathway, only GlcN is able to induce circadian phase delay both in vitro and in vivo. 37169147 1 22 theme Circadian 102:110 arg1 rhythms 112:118 Circadian rhythms 102:118 Circadian rhythms 102:118 Circadian rhythms are closely linked to the metabolic network through circadian feedback regulation. 37169147 3 23 theme phase 555:559 arg1 delay 561:565 circadian phase delay 545:565 circadian phase delay 545:565 Here, we found out that, among the downstream metabolites regulated by d-glucosamine (GlcN) in HBP salvage pathway, only GlcN is able to induce circadian phase delay both in vitro and in vivo. 37169147 3 24 theme only 517:520 arg1 GlcN 522:525 only GlcN 517:525 only GlcN 517:525 Here, we found out that, among the downstream metabolites regulated by d-glucosamine (GlcN) in HBP salvage pathway, only GlcN is able to induce circadian phase delay both in vitro and in vivo. 37169147 7 25 theme future 1114:1119 arg1 treatment 1121:1129 the future treatment 1110:1129 the future treatment of shift work and circadian misalignment 1110:1170 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 7 26 theme circadian 1149:1157 arg1 misalignment 1159:1170 circadian misalignment 1149:1170 circadian misalignment 1149:1170 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 5 27 theme mTOR 781:784 arg1 pathway 796:802 mTOR signaling pathway 781:802 mTOR signaling pathway 781:802 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 7 28 theme therapeutic 1050:1060 arg1 potential 1062:1070 the therapeutic potential 1046:1070 the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment 1046:1170 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 7 29 from drug 1102:1105 arg1 treatment 1121:1129 the future treatment 1110:1129 the future treatment of shift work and circadian misalignment 1110:1170 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 0 30 theme BMAL1 57:61 arg1 degradation 63:73 BMAL1 degradation 57:73 BMAL1 degradation 57:73 d-Glucosamine induces circadian phase delay by promoting BMAL1 degradation through AMPK/mTOR pathway. 37169147 5 31 theme mouse 869:873 arg1 tissues 875:881 mouse tissues 869:881 mouse tissues 869:881 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 7 32 theme clock 1022:1026 arg1 phase 1028:1032 clock phase 1022:1032 clock phase 1022:1032 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 3 33 theme HBP 496:498 arg1 pathway 508:514 HBP salvage pathway 496:514 HBP salvage pathway 496:514 Here, we found out that, among the downstream metabolites regulated by d-glucosamine (GlcN) in HBP salvage pathway, only GlcN is able to induce circadian phase delay both in vitro and in vivo. 37169147 5 34 theme pathway 796:802 arg1 inhibition 767:776 the inhibition 763:776 the inhibition of mTOR signaling pathway 763:802 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 6 35 theme BMAL1 908:912 arg1 degradation 914:924 BMAL1 degradation 908:924 BMAL1 degradation 908:924 Moreover, GlcN promoted BMAL1 degradation via proteasome pathway. 37169147 5 36 dep p-BMAL1 833:839 arg1 both 841:844 both 841:844 both 841:844 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 3 37 theme salvage 500:506 arg1 pathway 508:514 HBP salvage pathway 496:514 HBP salvage pathway 496:514 Here, we found out that, among the downstream metabolites regulated by d-glucosamine (GlcN) in HBP salvage pathway, only GlcN is able to induce circadian phase delay both in vitro and in vivo. 37169147 2 38 link O-linked 322:329 arg1 O-GlcNAcylation 365:379 O-GlcNAcylation 365:379 O-GlcNAcylation 365:379 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 2 38 link O-linked 322:329 arg1 N-acetylglucosamine 331:349 the O-linked N-acetylglucosamine 318:349 the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins 318:398 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 5 39 dep up-regulates 722:733 arg1 leading 752:758 leading 752:758 leading to the inhibition of mTOR signaling pathway 752:802 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 5 39 dep up-regulates 722:733 arg1 down-regulation 814:828 down-regulation 814:828 down-regulation of p-BMAL1 both in human cell line and mouse tissues 814:881 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 2 40 theme metabolism 268:277 arg1 pathway 231:237 The hexosamine biosynthetic pathway 203:237 The hexosamine biosynthetic pathway (HBP) 203:243 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 2 40 theme metabolism 268:277 arg1 branch 250:255 a branch 248:255 a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins 248:398 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 7 41 theme GlcN 1003:1006 arg1 mechanism 990:998 a novel molecular mechanism 972:998 a novel molecular mechanism of GlcN in regulating clock phase 972:1032 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 2 42 dep N-acetylglucosamine 331:349 arg1 modification 351:362 modification 351:362 the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins 318:398 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 2 43 theme biosynthetic 218:229 arg1 HBP 240:242 HBP 240:242 HBP 240:242 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 2 43 theme biosynthetic 218:229 arg1 pathway 231:237 The hexosamine biosynthetic pathway 203:237 The hexosamine biosynthetic pathway (HBP) 203:243 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 2 43 theme biosynthetic 218:229 arg1 branch 250:255 a branch 248:255 a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins 248:398 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 2 44 theme glucose 260:266 arg1 metabolism 268:277 glucose metabolism 260:277 glucose metabolism 260:277 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 7 45 theme molecular 980:988 arg1 mechanism 990:998 a novel molecular mechanism 972:998 a novel molecular mechanism of GlcN in regulating clock phase 972:1032 These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment. 37169147 2 46 theme hexosamine 207:216 arg1 HBP 240:242 HBP 240:242 HBP 240:242 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 2 46 theme hexosamine 207:216 arg1 pathway 231:237 The hexosamine biosynthetic pathway 203:237 The hexosamine biosynthetic pathway (HBP) 203:243 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 2 46 theme hexosamine 207:216 arg1 branch 250:255 a branch 248:255 a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins 248:398 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 1 47 theme metabolic 146:154 arg1 network 156:162 the metabolic network 142:162 the metabolic network 142:162 Circadian rhythms are closely linked to the metabolic network through circadian feedback regulation. 37169147 5 48 theme signaling 786:794 arg1 pathway 796:802 mTOR signaling pathway 781:802 mTOR signaling pathway 781:802 Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. 37169147 1 49 attach linked 132:137 arg1 network 156:162 the metabolic network 142:162 the metabolic network 142:162 Circadian rhythms are closely linked to the metabolic network through circadian feedback regulation. 37169147 1 49 attach linked 132:137 arg2 rhythms 112:118 Circadian rhythms 102:118 Circadian rhythms 102:118 Circadian rhythms are closely linked to the metabolic network through circadian feedback regulation. 37169147 0 50 theme circadian 22:30 arg1 delay 38:42 circadian phase delay 22:42 circadian phase delay 22:42 d-Glucosamine induces circadian phase delay by promoting BMAL1 degradation through AMPK/mTOR pathway. 37169147 2 51 theme proteins 391:398 arg1 O-GlcNAcylation 365:379 O-GlcNAcylation 365:379 O-GlcNAcylation 365:379 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 2 51 theme proteins 391:398 arg1 N-acetylglucosamine 331:349 the O-linked N-acetylglucosamine 318:349 the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins 318:398 The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. 37169147 6 52 theme proteasome 930:939 arg1 pathway 941:947 proteasome pathway 930:947 proteasome pathway 930:947 Moreover, GlcN promoted BMAL1 degradation via proteasome pathway. 37169147 4 53 theme Mechanistic 594:604 arg1 studies 606:612 Mechanistic studies 594:612 Mechanistic studies 594:612 Mechanistic studies indicated that the phase-shift induced by GlcN is independent of O-GlcNAcylation. 36551191 1 0 theme O-linked 385:392 arg1 N-acetylglucosamine 394:412 O-linked N-acetylglucosamine 385:412 O-linked N-acetylglucosamine (O-GlcNAc) 385:423 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 1 0 theme O-linked 385:392 arg1 O-GlcNAc 415:422 O-GlcNAc 415:422 O-GlcNAc 415:422 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 2 1 theme culture 670:676 arg1 media 678:682 serum-contained and serum-free cell culture media 634:682 media 678:682 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 4 2 theme serum-free 1039:1048 arg1 medium 1050:1055 a serum-free medium 1037:1055 a serum-free medium 1037:1055 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 0 3 theme HL-60 89:93 arg1 Cells 95:99 Human Promyelocytic HL-60 Cells 69:99 Human Promyelocytic HL-60 Cells 69:99 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation. 36551191 0 4 from Regulation 18:27 arg1 Cells 95:99 Human Promyelocytic HL-60 Cells 69:99 Human Promyelocytic HL-60 Cells 69:99 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation. 36551191 2 5 theme cell 665:668 arg1 media 678:682 serum-contained and serum-free cell culture media 634:682 media 678:682 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 4 6 dep galectins 987:995 arg1 -9 1006:1007 -9 1006:1007 -9 1006:1007 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 4 6 dep galectins 987:995 arg1 -10 1014:1016 -10 1014:1016 -10 1014:1016 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 5 7 theme O-GlcNAc 1274:1281 arg1 homeostasis 1283:1293 O-GlcNAc homeostasis 1274:1293 O-GlcNAc homeostasis 1274:1293 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 5 8 theme unconventional 1477:1490 arg1 mechanisms 1502:1511 unconventional secretion mechanisms 1477:1511 unconventional secretion mechanisms 1477:1511 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 0 9 theme Neutrophilic 112:123 arg1 Differentiation 125:139 Neutrophilic Differentiation 112:139 Neutrophilic Differentiation 112:139 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation. 36551191 5 10 theme protein 1419:1425 arg1 family 1427:1432 this protein family 1414:1432 this protein family 1414:1432 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 2 11 theme serum-free 654:663 arg1 media 678:682 serum-contained and serum-free cell culture media 634:682 media 678:682 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 1 12 with proteins 371:378 arg1 N-acetylglucosamine 394:412 O-linked N-acetylglucosamine 385:412 O-linked N-acetylglucosamine (O-GlcNAc) 385:423 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 1 12 with proteins 371:378 arg1 O-GlcNAc 415:422 O-GlcNAc 415:422 O-GlcNAc 415:422 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 3 13 theme serum 928:932 arg1 absence 917:923 absence 917:923 absence 917:923 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 3 13 theme serum 928:932 arg1 presence 905:912 presence 905:912 presence 905:912 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 4 14 theme galectins 987:995 arg1 secretion 969:977 The secretion 965:977 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium 965:1055 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 5 15 theme galectin 1335:1342 arg1 expression 1344:1353 galectin expression 1335:1353 galectin expression in cells 1335:1362 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 2 16 theme all-trans 496:504 arg1 ATRA 521:524 ATRA 521:524 ATRA 521:524 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 2 16 theme all-trans 496:504 arg1 acid 515:518 all-trans retinoic acid 496:518 all-trans retinoic acid (ATRA) 496:525 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 1 17 theme homeostatic 285:295 arg1 regulation 297:306 homeostatic regulation 285:306 homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) 285:423 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 5 18 theme expression 1344:1353 arg1 regulation 1321:1330 regulation 1321:1330 regulation of galectin expression in cells 1321:1362 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 5 19 theme important 1451:1459 arg1 aspect 1467:1472 an important novel aspect 1448:1472 an important novel aspect of unconventional secretion mechanisms 1448:1511 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 5 19 theme important 1451:1459 arg1 secretion 1381:1389 the secretion 1377:1389 the secretion 1377:1389 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 3 20 from profiles 722:729 arg1 cells 740:744 HL-60 cells 734:744 HL-60 cells 734:744 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 5 21 theme novel 1461:1465 arg1 aspect 1467:1472 an important novel aspect 1448:1472 an important novel aspect of unconventional secretion mechanisms 1448:1511 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 5 21 theme novel 1461:1465 arg1 secretion 1381:1389 the secretion 1377:1389 the secretion 1377:1389 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 4 22 theme galectins 1216:1224 arg1 levels 1192:1197 the basal levels 1182:1197 the basal levels of extracellular galectins 1182:1224 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 2 23 theme retinoic 506:513 arg1 ATRA 521:524 ATRA 521:524 ATRA 521:524 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 2 23 theme retinoic 506:513 arg1 acid 515:518 all-trans retinoic acid 496:518 all-trans retinoic acid (ATRA) 496:525 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 2 24 theme neutrophilic 441:452 arg1 differentiation 454:468 neutrophilic differentiation 441:468 neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) 441:562 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 3 25 theme cycle 811:815 arg1 enzymes 817:823 O-GlcNAc cycle enzymes 802:823 O-GlcNAc cycle enzymes 802:823 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 4 26 theme extracellular 1202:1214 arg1 galectins 1216:1224 extracellular galectins 1202:1224 extracellular galectins 1202:1224 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 3 27 from gene 694:697 arg1 cells 740:744 HL-60 cells 734:744 HL-60 cells 734:744 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 0 28 theme O-GlcNAc-Mediated 0:16 arg1 Regulation 18:27 O-GlcNAc-Mediated Regulation 0:27 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells 0:99 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation. 36551191 3 29 theme enzymes 817:823 arg1 inhibitors 788:797 inhibitors 788:797 inhibitors of O-GlcNAc cycle enzymes 788:823 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 5 30 theme family 1427:1432 arg1 members 1403:1409 multiple members 1394:1409 multiple members of this protein family 1394:1432 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 4 31 theme HL-60 1022:1026 arg1 cells 1028:1032 HL-60 cells 1022:1032 HL-60 cells 1022:1032 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 5 32 theme secretion 1492:1500 arg1 mechanisms 1502:1511 unconventional secretion mechanisms 1477:1511 unconventional secretion mechanisms 1477:1511 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 0 33 theme Galectin 32:39 arg1 Expression 41:50 Galectin Expression 32:50 Galectin Expression 32:50 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation. 36551191 2 34 theme cellular 606:613 arg1 levels 624:629 cellular O-GlcNAc levels 606:629 cellular O-GlcNAc levels 606:629 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 3 35 theme O-GlcNAc 802:809 arg1 enzymes 817:823 O-GlcNAc cycle enzymes 802:823 O-GlcNAc cycle enzymes 802:823 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 3 36 theme expression 711:720 arg1 profiles 722:729 Galectin gene and protein expression profiles 685:729 profiles 722:729 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 4 37 theme O-GlcNAc-elevating 1112:1129 arg1 G 1139:1139 O-GlcNAc-elevating thiamet G 1112:1139 O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) 1112:1163 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 4 37 theme O-GlcNAc-elevating 1112:1129 arg1 inhibitor 1154:1162 O-GlcNAcase inhibitor 1142:1162 O-GlcNAcase inhibitor 1142:1162 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 4 38 theme thiamet 1131:1137 arg1 G 1139:1139 O-GlcNAc-elevating thiamet G 1112:1139 O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) 1112:1163 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 4 38 theme thiamet 1131:1137 arg1 inhibitor 1154:1162 O-GlcNAcase inhibitor 1142:1162 O-GlcNAcase inhibitor 1142:1162 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 2 39 theme cells 479:483 arg1 differentiation 454:468 neutrophilic differentiation 441:468 neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) 441:562 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 3 40 theme overall 834:840 arg1 trends 842:847 overall trends 834:847 overall trends for each drug 834:861 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 1 41 theme post-translational 322:339 arg1 modification 341:352 the post-translational modification 318:352 the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) 318:423 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 1 42 link O-linked 385:392 arg1 N-acetylglucosamine 394:412 O-linked N-acetylglucosamine 385:412 O-linked N-acetylglucosamine (O-GlcNAc) 385:423 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 1 42 link O-linked 385:392 arg1 O-GlcNAc 415:422 O-GlcNAc 415:422 O-GlcNAc 415:422 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 2 43 theme HL-60 473:477 arg1 cells 479:483 HL-60 cells 473:483 HL-60 cells 473:483 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 0 44 theme Expression 41:50 arg1 Regulation 18:27 O-GlcNAc-Mediated Regulation 0:27 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells 0:99 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation. 36551191 2 45 theme significant 586:596 arg1 drop 598:601 a significant drop 584:601 a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media 584:682 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 4 46 from secretion 969:977 arg1 medium 1050:1055 a serum-free medium 1037:1055 a serum-free medium 1037:1055 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 1 47 dep expression 196:205 arg1 the 192:194 the 192:194 the 192:194 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 4 48 theme basal 1186:1190 arg1 levels 1192:1197 the basal levels 1182:1197 the basal levels of extracellular galectins 1182:1224 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 1 49 theme galectins 224:232 arg1 secretion 211:219 secretion 211:219 secretion 211:219 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 1 49 theme galectins 224:232 arg1 expression 196:205 expression 196:205 expression 196:205 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 2 50 theme serum-contained 634:648 arg1 media 678:682 serum-contained and serum-free cell culture media 634:682 media 678:682 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 3 51 theme protein 703:709 arg1 profiles 722:729 Galectin gene and protein expression profiles 685:729 profiles 722:729 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 5 52 theme multiple 1394:1401 arg1 members 1403:1409 multiple members 1394:1409 multiple members of this protein family 1394:1432 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 0 53 theme Secretion 56:64 arg1 Regulation 18:27 O-GlcNAc-Mediated Regulation 0:27 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells 0:99 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation. 36551191 1 54 theme intracellular 357:369 arg1 proteins 371:378 intracellular proteins 357:378 intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) 357:423 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 3 55 mod modified 764:771 arg1 profiles 722:729 Galectin gene and protein expression profiles 685:729 profiles 722:729 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 3 55 mod modified 764:771 arg3 ATRA 776:779 ATRA 776:779 ATRA 776:779 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 3 55 mod modified 764:771 arg1 gene 694:697 Galectin gene and protein expression profiles 685:729 gene 694:697 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 5 56 from regulation 1321:1330 arg1 cells 1358:1362 cells 1358:1362 cells 1358:1362 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 5 57 theme members 1403:1409 arg1 aspect 1467:1472 an important novel aspect 1448:1472 an important novel aspect of unconventional secretion mechanisms 1448:1511 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 5 57 theme members 1403:1409 arg1 secretion 1381:1389 the secretion 1377:1389 the secretion 1377:1389 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 5 58 theme mechanisms 1502:1511 arg1 aspect 1467:1472 an important novel aspect 1448:1472 an important novel aspect of unconventional secretion mechanisms 1448:1511 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 5 58 theme mechanisms 1502:1511 arg1 secretion 1381:1389 the secretion 1377:1389 the secretion 1377:1389 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 4 59 theme O-GlcNAc-reducing 1075:1091 arg1 ATRA 1093:1096 O-GlcNAc-reducing ATRA 1075:1096 O-GlcNAc-reducing ATRA 1075:1096 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 1 60 theme proteins 371:378 arg1 modification 341:352 the post-translational modification 318:352 the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) 318:423 In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). 36551191 2 61 theme levels 624:629 arg1 drop 598:601 a significant drop 584:601 a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media 584:682 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 5 62 from cells 1358:1362 arg1 regulation 1321:1330 regulation 1321:1330 regulation of galectin expression in cells 1321:1362 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 3 63 theme Galectin 685:692 arg1 gene 694:697 Galectin gene and protein expression profiles 685:729 gene 694:697 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 3 64 dep presence 905:912 arg1 the 901:903 the 901:903 the 901:903 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 2 65 from drop 598:601 arg1 media 678:682 serum-contained and serum-free cell culture media 634:682 media 678:682 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 2 66 theme O-GlcNAc 615:622 arg1 levels 624:629 cellular O-GlcNAc levels 606:629 cellular O-GlcNAc levels 606:629 We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. 36551191 4 67 theme O-GlcNAcase 1142:1152 arg1 G 1139:1139 O-GlcNAc-elevating thiamet G 1112:1139 O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) 1112:1163 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 4 67 theme O-GlcNAcase 1142:1152 arg1 inhibitor 1154:1162 O-GlcNAcase inhibitor 1142:1162 O-GlcNAcase inhibitor 1142:1162 The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. 36551191 0 68 theme Promyelocytic 75:87 arg1 Cells 95:99 Human Promyelocytic HL-60 Cells 69:99 Human Promyelocytic HL-60 Cells 69:99 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation. 36551191 3 69 theme HL-60 734:738 arg1 cells 740:744 HL-60 cells 734:744 HL-60 cells 734:744 Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. 36551191 5 70 from expression 1344:1353 arg1 cells 1358:1362 cells 1358:1362 cells 1358:1362 Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms. 36551191 0 71 theme Human 69:73 arg1 Cells 95:99 Human Promyelocytic HL-60 Cells 69:99 Human Promyelocytic HL-60 Cells 69:99 O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation. 37291168 0 0 theme male 99:102 arg1 mice 104:107 male mice 99:107 male mice 99:107 Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice. 37291168 1 1 link O-linked 228:235 arg1 O-GlcNAc 245:252 O-GlcNAc 245:252 O-GlcNAc 245:252 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 1 1 link O-linked 228:235 arg1 GlcNAc 237:242 O-linked GlcNAc 228:242 O-linked GlcNAc (O-GlcNAc) protein modifications 228:275 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 4 2 from observations 874:885 arg1 mice 895:898 male mice 890:898 male mice 890:898 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 1 3 theme uridine 161:167 arg1 UDP-GlcNAc 202:211 UDP-GlcNAc 202:211 UDP-GlcNAc 202:211 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 1 3 theme uridine 161:167 arg1 N-acetylglucosamine 181:199 uridine diphosphate N-acetylglucosamine 161:199 uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses 161:337 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 6 4 theme unfolded 1086:1093 arg1 UPRE 1121:1124 UPRE 1121:1124 UPRE 1121:1124 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 6 4 theme unfolded 1086:1093 arg1 element 1112:1118 a conserved unfolded protein response element 1074:1118 a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1074:1195 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 7 5 from cleavage 1321:1328 arg1 heart 1372:1376 the heart 1368:1376 the heart 1368:1376 Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. 37291168 1 6 theme diphosphate 169:179 arg1 UDP-GlcNAc 202:211 UDP-GlcNAc 202:211 UDP-GlcNAc 202:211 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 1 6 theme diphosphate 169:179 arg1 N-acetylglucosamine 181:199 uridine diphosphate N-acetylglucosamine 161:199 uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses 161:337 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 6 7 theme conserved 1076:1084 arg1 UPRE 1121:1124 UPRE 1121:1124 UPRE 1121:1124 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 6 7 theme conserved 1076:1084 arg1 element 1112:1118 a conserved unfolded protein response element 1074:1118 a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1074:1195 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 8 8 theme transcription 1496:1508 arg1 Tisp40 1446:1451 Tisp40 1446:1451 Tisp40 1446:1451 Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury. 37291168 8 8 theme transcription 1496:1508 arg1 factor 1510:1515 a cardiomyocyte-enriched UPR-associated transcription factor 1456:1515 a cardiomyocyte-enriched UPR-associated transcription factor 1456:1515 Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury. 37291168 7 9 from accumulation 1342:1353 arg1 heart 1372:1376 the heart 1368:1376 the heart 1368:1376 Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. 37291168 3 10 theme cardiac 591:597 arg1 injury 626:631 cardiac ischemia/reperfusion (I/R) injury 591:631 cardiac ischemia/reperfusion (I/R) injury 591:631 Here, we show that Tisp40 expression, cleavage and nuclear accumulation are increased by cardiac ischemia/reperfusion (I/R) injury. 37291168 6 11 theme protein 1249:1255 arg1 modifications 1257:1269 O-GlcNAc protein modifications 1240:1269 O-GlcNAc protein modifications 1240:1269 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 5 12 from addition 904:911 arg1 sufficient 950:959 sufficient 950:959 sufficient 950:959 In addition, overexpression of nuclear Tisp40 is sufficient to attenuate cardiac I/R injury in vivo and in vitro. 37291168 7 13 theme nuclear 1334:1340 arg1 accumulation 1342:1353 nuclear accumulation 1334:1353 nuclear accumulation of Tisp40 in the heart 1334:1376 Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. 37291168 5 14 theme nuclear 932:938 arg1 Tisp40 940:945 nuclear Tisp40 932:945 nuclear Tisp40 932:945 In addition, overexpression of nuclear Tisp40 is sufficient to attenuate cardiac I/R injury in vivo and in vitro. 37291168 4 15 theme cardiac 789:795 arg1 injury 797:802 acute cardiac injury 783:802 acute cardiac injury 783:802 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 3 16 theme nuclear 553:559 arg1 accumulation 561:572 nuclear accumulation 553:572 nuclear accumulation 553:572 Here, we show that Tisp40 expression, cleavage and nuclear accumulation are increased by cardiac ischemia/reperfusion (I/R) injury. 37291168 4 17 theme oxidative 751:759 arg1 stress 761:766 I/R-induced oxidative stress 739:766 I/R-induced oxidative stress 739:766 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 2 18 theme membrane-resident 417:433 arg1 factor 449:454 an endoplasmic reticulum membrane-resident transcription factor 392:454 an endoplasmic reticulum membrane-resident transcription factor 392:454 Transcript induced in spermiogenesis 40 (Tisp40) is an endoplasmic reticulum membrane-resident transcription factor and plays critical roles in cell homeostasis. 37291168 6 19 theme GFPT1 1181:1185 arg1 promoter 1188:1195 the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1130:1195 the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1130:1195 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 2 20 theme reticulum 407:415 arg1 factor 449:454 an endoplasmic reticulum membrane-resident transcription factor 392:454 an endoplasmic reticulum membrane-resident transcription factor 392:454 Transcript induced in spermiogenesis 40 (Tisp40) is an endoplasmic reticulum membrane-resident transcription factor and plays critical roles in cell homeostasis. 37291168 2 21 theme cell 484:487 arg1 homeostasis 489:499 cell homeostasis 484:499 cell homeostasis 484:499 Transcript induced in spermiogenesis 40 (Tisp40) is an endoplasmic reticulum membrane-resident transcription factor and plays critical roles in cell homeostasis. 37291168 7 22 theme Tisp40 1358:1363 arg1 cleavage 1321:1328 cleavage 1321:1328 cleavage 1321:1328 Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. 37291168 7 22 theme Tisp40 1358:1363 arg1 accumulation 1342:1353 nuclear accumulation 1334:1353 nuclear accumulation of Tisp40 in the heart 1334:1376 Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. 37291168 7 22 theme Tisp40 1358:1363 arg1 upregulation 1307:1318 I/R-induced upregulation 1295:1318 I/R-induced upregulation 1295:1318 Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. 37291168 3 23 theme ischemia/reperfusion 599:618 arg1 injury 626:631 cardiac ischemia/reperfusion (I/R) injury 591:631 cardiac ischemia/reperfusion (I/R) injury 591:631 Here, we show that Tisp40 expression, cleavage and nuclear accumulation are increased by cardiac ischemia/reperfusion (I/R) injury. 37291168 2 24 theme endoplasmic 395:405 arg1 reticulum 407:415 an endoplasmic reticulum 392:415 an endoplasmic reticulum membrane-resident transcription factor 392:454 Transcript induced in spermiogenesis 40 (Tisp40) is an endoplasmic reticulum membrane-resident transcription factor and plays critical roles in cell homeostasis. 37291168 6 25 theme O-GlcNAc 1240:1247 arg1 modifications 1257:1269 O-GlcNAc protein modifications 1240:1269 O-GlcNAc protein modifications 1240:1269 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 4 26 theme I/R-induced 739:749 arg1 stress 761:766 I/R-induced oxidative stress 739:766 I/R-induced oxidative stress 739:766 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 0 27 theme ischemia/reperfusion 24:43 arg1 injury 45:50 cardiac ischemia/reperfusion injury 16:50 cardiac ischemia/reperfusion injury 16:50 Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice. 37291168 1 28 theme cell 303:306 arg1 survival 308:315 cell survival 303:315 cell survival 303:315 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 7 29 theme endoplasmic 1394:1404 arg1 reticulum 1406:1414 endoplasmic reticulum 1394:1414 endoplasmic reticulum stress 1394:1421 Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. 37291168 2 30 theme critical 466:473 arg1 roles 475:479 critical roles 466:479 critical roles 466:479 Transcript induced in spermiogenesis 40 (Tisp40) is an endoplasmic reticulum membrane-resident transcription factor and plays critical roles in cell homeostasis. 37291168 4 31 theme long-term 864:872 arg1 observations 874:885 long-term observations 864:885 long-term observations in male mice 864:898 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 1 32 theme hexosamine 114:123 arg1 HBP 147:149 HBP 147:149 HBP 147:149 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 1 32 theme hexosamine 114:123 arg1 pathway 138:144 The hexosamine biosynthetic pathway 110:144 The hexosamine biosynthetic pathway (HBP) 110:150 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 7 33 theme reticulum 1406:1414 arg1 stress 1416:1421 endoplasmic reticulum stress 1394:1421 endoplasmic reticulum stress 1394:1421 Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. 37291168 4 34 theme acute 783:787 arg1 injury 797:802 acute cardiac injury 783:802 acute cardiac injury 783:802 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 4 35 theme Tisp40 705:710 arg1 overexpression 712:725 cardiomyocyte-restricted Tisp40 overexpression 680:725 cardiomyocyte-restricted Tisp40 overexpression 680:725 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 4 36 theme cardiomyocyte-restricted 680:703 arg1 overexpression 712:725 cardiomyocyte-restricted Tisp40 overexpression 680:725 cardiomyocyte-restricted Tisp40 overexpression 680:725 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 6 37 theme glutamine-fructose-6-phosphate 1134:1163 arg1 promoter 1188:1195 the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1130:1195 the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1130:1195 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 1 38 theme O-linked 228:235 arg1 O-GlcNAc 245:252 O-GlcNAc 245:252 O-GlcNAc 245:252 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 1 38 theme O-linked 228:235 arg1 GlcNAc 237:242 O-linked GlcNAc 228:242 O-linked GlcNAc (O-GlcNAc) protein modifications 228:275 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 6 39 theme transaminase 1165:1176 arg1 promoter 1188:1195 the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1130:1195 the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1130:1195 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 1 40 theme lethal 323:328 arg1 stresses 330:337 lethal stresses 323:337 lethal stresses 323:337 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 0 41 from pathway 88:94 arg1 mice 104:107 male mice 99:107 male mice 99:107 Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice. 37291168 6 42 theme protein 1095:1101 arg1 UPRE 1121:1124 UPRE 1121:1124 UPRE 1121:1124 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 6 42 theme protein 1095:1101 arg1 element 1112:1118 a conserved unfolded protein response element 1074:1118 a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1074:1195 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 5 43 theme Tisp40 940:945 arg1 overexpression 914:927 overexpression 914:927 overexpression of nuclear Tisp40 914:945 In addition, overexpression of nuclear Tisp40 is sufficient to attenuate cardiac I/R injury in vivo and in vitro. 37291168 1 44 theme GlcNAc 237:242 arg1 modifications 263:275 O-linked GlcNAc (O-GlcNAc) protein modifications 228:275 O-linked GlcNAc (O-GlcNAc) protein modifications 228:275 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 0 45 theme hexosamine 64:73 arg1 pathway 88:94 the hexosamine biosynthetic pathway 60:94 the hexosamine biosynthetic pathway in male mice 60:107 Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice. 37291168 8 46 theme UPR-associated 1481:1494 arg1 Tisp40 1446:1451 Tisp40 1446:1451 Tisp40 1446:1451 Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury. 37291168 8 46 theme UPR-associated 1481:1494 arg1 factor 1510:1515 a cardiomyocyte-enriched UPR-associated transcription factor 1456:1515 a cardiomyocyte-enriched UPR-associated transcription factor 1456:1515 Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury. 37291168 8 47 theme cardiac 1584:1590 arg1 injury 1596:1601 cardiac I/R injury 1584:1601 cardiac I/R injury 1584:1601 Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury. 37291168 8 48 theme cardiomyocyte-enriched 1458:1479 arg1 Tisp40 1446:1451 Tisp40 1446:1451 Tisp40 1446:1451 Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury. 37291168 8 48 theme cardiomyocyte-enriched 1458:1479 arg1 factor 1510:1515 a cardiomyocyte-enriched UPR-associated transcription factor 1456:1515 a cardiomyocyte-enriched UPR-associated transcription factor 1456:1515 Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury. 37291168 1 49 theme biosynthetic 125:136 arg1 HBP 147:149 HBP 147:149 HBP 147:149 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 1 49 theme biosynthetic 125:136 arg1 pathway 138:144 The hexosamine biosynthetic pathway 110:144 The hexosamine biosynthetic pathway (HBP) 110:150 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37291168 6 50 theme Mechanistic 1015:1025 arg1 studies 1027:1033 Mechanistic studies 1015:1033 Mechanistic studies 1015:1033 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 7 51 from upregulation 1307:1318 arg1 heart 1372:1376 the heart 1368:1376 the heart 1368:1376 Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. 37291168 8 52 theme targeting 1522:1530 arg1 Tisp40 1532:1537 targeting Tisp40 1522:1537 targeting Tisp40 1522:1537 Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury. 37291168 7 53 theme I/R-induced 1295:1305 arg1 upregulation 1307:1318 I/R-induced upregulation 1295:1318 I/R-induced upregulation 1295:1318 Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. 37291168 3 54 theme Tisp40 521:526 arg1 expression 528:537 Tisp40 expression 521:537 Tisp40 expression 521:537 Here, we show that Tisp40 expression, cleavage and nuclear accumulation are increased by cardiac ischemia/reperfusion (I/R) injury. 37291168 4 55 theme male 890:893 arg1 mice 895:898 male mice 890:898 male mice 890:898 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 4 56 theme Tisp40 641:646 arg1 deficiency 648:657 Global Tisp40 deficiency 634:657 Global Tisp40 deficiency 634:657 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 5 57 from sufficient 950:959 arg1 addition 904:911 addition 904:911 addition 904:911 In addition, overexpression of nuclear Tisp40 is sufficient to attenuate cardiac I/R injury in vivo and in vitro. 37291168 8 58 theme effective 1551:1559 arg1 approaches 1561:1570 effective approaches 1551:1570 effective approaches 1551:1570 Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury. 37291168 4 59 theme cardiac 819:825 arg1 remodeling 827:836 cardiac remodeling 819:836 cardiac remodeling 819:836 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 6 60 theme promoter 1188:1195 arg1 UPRE 1121:1124 UPRE 1121:1124 UPRE 1121:1124 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 6 60 theme promoter 1188:1195 arg1 element 1112:1118 a conserved unfolded protein response element 1074:1118 a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1074:1195 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 6 61 theme HBP 1227:1229 arg1 flux 1231:1234 HBP flux 1227:1234 HBP flux 1227:1234 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 4 62 theme Global 634:639 arg1 deficiency 648:657 Global Tisp40 deficiency 634:657 Global Tisp40 deficiency 634:657 Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. 37291168 8 63 theme I/R 1592:1594 arg1 injury 1596:1601 cardiac I/R injury 1584:1601 cardiac I/R injury 1584:1601 Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury. 37291168 2 64 theme transcription 435:447 arg1 factor 449:454 an endoplasmic reticulum membrane-resident transcription factor 392:454 an endoplasmic reticulum membrane-resident transcription factor 392:454 Transcript induced in spermiogenesis 40 (Tisp40) is an endoplasmic reticulum membrane-resident transcription factor and plays critical roles in cell homeostasis. 37291168 5 65 theme cardiac 974:980 arg1 injury 986:991 cardiac I/R injury 974:991 cardiac I/R injury 974:991 In addition, overexpression of nuclear Tisp40 is sufficient to attenuate cardiac I/R injury in vivo and in vitro. 37291168 6 66 theme response 1103:1110 arg1 UPRE 1121:1124 UPRE 1121:1124 UPRE 1121:1124 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 6 66 theme response 1103:1110 arg1 element 1112:1118 a conserved unfolded protein response element 1074:1118 a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter 1074:1195 Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. 37291168 0 67 theme biosynthetic 75:86 arg1 pathway 88:94 the hexosamine biosynthetic pathway 60:94 the hexosamine biosynthetic pathway in male mice 60:107 Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice. 37291168 0 68 theme cardiac 16:22 arg1 injury 45:50 cardiac ischemia/reperfusion injury 16:50 cardiac ischemia/reperfusion injury 16:50 Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice. 37291168 5 69 theme I/R 982:984 arg1 injury 986:991 cardiac I/R injury 974:991 cardiac I/R injury 974:991 In addition, overexpression of nuclear Tisp40 is sufficient to attenuate cardiac I/R injury in vivo and in vitro. 37291168 1 70 theme protein 255:261 arg1 modifications 263:275 O-linked GlcNAc (O-GlcNAc) protein modifications 228:275 O-linked GlcNAc (O-GlcNAc) protein modifications 228:275 The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. 37149632 7 0 gly glycoprotein 1607:1618 arg1 glycoprotein 1607:1618 bacterial glycoprotein vaccine preparation 1597:1638 bacterial glycoprotein vaccine preparation 1597:1638 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 5 1 theme cluster 1156:1162 arg1 deletion 1128:1135 the deletion 1124:1135 the deletion of the yfdGHI gene cluster 1124:1162 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 6 2 theme successful 1296:1305 arg1 preparation 1307:1317 the successful preparation 1292:1317 the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP) 1292:1391 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 5 3 gly glycoproteins 1192:1204 arg1 glycoproteins 1192:1204 glycoproteins 1192:1204 glycoproteins 1192:1204 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 2 4 theme chassis 386:392 arg1 cells 394:398 chassis cells 386:398 chassis cells for conjugate nanovaccines 386:425 Nanovaccines have also entered the vaccine development arena with advances in nanotechnology and have been significantly developed, but chassis cells for conjugate nanovaccines have not been reported. 37149632 4 5 with nanocarriers 899:910 arg1 form 952:955 form 952:955 exposed SpyTag in vitro to form conjugate nanovaccines 925:978 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 4 5 with nanocarriers 899:910 arg1 SpyTag 933:938 SpyTag 933:938 SpyTag 933:938 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 4 5 with nanocarriers 899:910 arg1 surface 917:923 surface 917:923 surface exposed SpyTag in vitro to form conjugate nanovaccines 917:978 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 7 6 theme convenient 1559:1568 arg1 framework 1583:1591 a convenient and reliable framework 1557:1591 a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile 1557:1669 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 7 6 theme convenient 1559:1568 arg1 flexible 1648:1655 flexible 1648:1655 flexible 1648:1655 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 7 7 theme glycoprotein 1607:1618 arg1 preparation 1628:1638 bacterial glycoprotein vaccine preparation 1597:1638 bacterial glycoprotein vaccine preparation 1597:1638 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 1 8 dep Engineered 114:123 arg1 BACKGROUND 103:112 BACKGROUND 103:112 BACKGROUND 103:112 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 7 9 theme chassis 1716:1722 arg1 cells 1724:1728 the engineered chassis cells 1701:1728 the engineered chassis cells 1701:1728 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 4 10 theme antigenic 798:806 arg1 polysaccharides 808:822 antigenic polysaccharides 798:822 antigenic polysaccharides produced by our bacterial chassis 798:856 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 4 11 theme targeted 770:777 arg1 glycoproteins 779:791 The targeted glycoproteins 766:791 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis 766:856 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 6 12 dep % 1478:1478 arg1 100 1475:1477 100 1475:1477 100 1475:1477 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 5 13 theme glycoprotein 1019:1030 arg1 yields 996:1001 the yields 992:1001 the yields of the targeted glycoprotein 992:1030 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 6 14 theme first 1281:1285 arg1 time 1287:1290 the first time 1277:1290 the first time 1277:1290 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 3 15 theme O-linked 581:588 arg1 PglL 610:613 O-linked glycosyltransferase PglL 581:613 O-linked glycosyltransferase PglL 581:613 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 7 16 theme cells 1724:1728 arg1 stability 1688:1696 the genomic stability 1676:1696 the genomic stability of the engineered chassis cells 1676:1728 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 4 17 theme proteinous 888:897 arg1 nanocarriers 899:910 proteinous nanocarriers 888:910 proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines 888:978 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 3 18 theme acceptor 560:567 arg1 protein 520:526 a generic recombinant protein 498:526 a generic recombinant protein (SpyCather4573) 498:542 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 18 theme acceptor 560:567 arg1 protein 569:575 the acceptor protein 556:575 the acceptor protein for O-linked glycosyltransferase PglL 556:613 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 19 dep Escherichia 640:650 arg1 coli 652:655 coli 652:655 coli 652:655 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 20 theme nanovaccine 473:483 arg1 preparation 485:495 nanovaccine preparation 473:495 nanovaccine preparation 473:495 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 21 link O-linked 581:588 arg1 PglL 610:613 O-linked glycosyltransferase PglL 581:613 O-linked glycosyltransferase PglL 581:613 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 6 22 theme nanovaccine 1370:1380 arg1 preparation 1307:1317 the successful preparation 1292:1317 the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP) 1292:1391 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 7 23 theme glycobiology 1785:1796 arg1 research 1798:1805 biosynthetic glycobiology research 1772:1805 biosynthetic glycobiology research 1772:1805 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 1 24 used used 163:166 arg2 strains 125:131 BACKGROUND Engineered strains 103:131 BACKGROUND Engineered strains of Escherichia coli 103:151 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 6 25 theme updated 1217:1223 arg1 system 1225:1230 the updated system 1213:1230 the updated system 1213:1230 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 5 26 theme yfdGHI 1144:1149 arg1 cluster 1156:1162 the yfdGHI gene cluster 1140:1162 the yfdGHI gene cluster 1140:1162 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 5 27 gly glycoprotein 1019:1030 arg1 glycoprotein 1019:1030 the targeted glycoprotein 1006:1030 the targeted glycoprotein 1006:1030 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 1 28 theme Protein 207:213 arg1 Technology 231:240 Protein Glycan Coupling Technology 207:240 Protein Glycan Coupling Technology (PGCT) 207:247 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 1 28 theme Protein 207:213 arg1 PGCT 243:246 PGCT 243:246 PGCT 243:246 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 7 29 dep CONCLUSIONS 1526:1536 arg1 promises 1730:1737 promises 1730:1737 promises a wide range of applications for biosynthetic glycobiology research 1730:1805 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 7 29 dep CONCLUSIONS 1526:1536 arg1 define 1550:1555 define 1550:1555 define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile 1550:1669 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 7 30 theme vaccine 1620:1626 arg1 preparation 1628:1638 bacterial glycoprotein vaccine preparation 1597:1638 bacterial glycoprotein vaccine preparation 1597:1638 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 1 31 theme Engineered 114:123 arg1 strains 125:131 BACKGROUND Engineered strains 103:131 BACKGROUND Engineered strains of Escherichia coli 103:151 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 2 32 theme conjugate 404:412 arg1 nanovaccines 414:425 conjugate nanovaccines 404:425 conjugate nanovaccines 404:425 Nanovaccines have also entered the vaccine development arena with advances in nanotechnology and have been significantly developed, but chassis cells for conjugate nanovaccines have not been reported. 37149632 0 33 theme Klebsiella 17:26 arg1 nanovaccine 49:59 a Klebsiella pneumoniae conjugate nanovaccine 15:59 a Klebsiella pneumoniae conjugate nanovaccine 15:59 Preparation of a Klebsiella pneumoniae conjugate nanovaccine using glycol-engineered Escherichia coli. 37149632 7 34 theme genomic 1680:1686 arg1 stability 1688:1696 the genomic stability 1676:1696 the genomic stability of the engineered chassis cells 1676:1728 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 6 35 theme conjugate 1360:1368 arg1 KPO1-VLP 1383:1390 KPO1-VLP 1383:1390 KPO1-VLP 1383:1390 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 6 35 theme conjugate 1360:1368 arg1 nanovaccine 1370:1380 an effective Klebsiella pneumoniae O1 conjugate nanovaccine 1322:1380 an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP) 1322:1391 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 7 36 theme biosynthetic 1772:1783 arg1 research 1798:1805 biosynthetic glycobiology research 1772:1805 biosynthetic glycobiology research 1772:1805 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 3 37 theme glycosyltransferase 590:608 arg1 PglL 610:613 O-linked glycosyltransferase PglL 581:613 O-linked glycosyltransferase PglL 581:613 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 5 38 theme deletion 1058:1065 arg1 experiments 1067:1077 gene cluster deletion experiments 1045:1077 gene cluster deletion experiments 1045:1077 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 3 39 theme generic 500:506 arg1 SpyCather4573 529:541 SpyCather4573 529:541 SpyCather4573 529:541 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 39 theme generic 500:506 arg1 protein 520:526 a generic recombinant protein 498:526 a generic recombinant protein (SpyCather4573) 498:542 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 39 theme generic 500:506 arg1 protein 569:575 the acceptor protein 556:575 the acceptor protein for O-linked glycosyltransferase PglL 556:613 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 6 40 theme O1 1357:1358 arg1 KPO1-VLP 1383:1390 KPO1-VLP 1383:1390 KPO1-VLP 1383:1390 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 6 40 theme O1 1357:1358 arg1 nanovaccine 1370:1380 an effective Klebsiella pneumoniae O1 conjugate nanovaccine 1322:1380 an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP) 1322:1391 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 1 41 theme bioconjugate 179:190 arg1 vaccines 192:199 bioconjugate vaccines 179:199 bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT) 179:247 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 6 42 theme virulent 1499:1506 arg1 challenge 1515:1523 virulent strain challenge 1499:1523 virulent strain challenge 1499:1523 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 3 43 theme recombinant 508:518 arg1 SpyCather4573 529:541 SpyCather4573 529:541 SpyCather4573 529:541 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 43 theme recombinant 508:518 arg1 protein 520:526 a generic recombinant protein 498:526 a generic recombinant protein (SpyCather4573) 498:542 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 43 theme recombinant 508:518 arg1 protein 569:575 the acceptor protein 556:575 the acceptor protein for O-linked glycosyltransferase PglL 556:613 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 0 44 theme conjugate 39:47 arg1 nanovaccine 49:59 a Klebsiella pneumoniae conjugate nanovaccine 15:59 a Klebsiella pneumoniae conjugate nanovaccine 15:59 Preparation of a Klebsiella pneumoniae conjugate nanovaccine using glycol-engineered Escherichia coli. 37149632 7 45 theme engineered 1705:1714 arg1 cells 1724:1728 the engineered chassis cells 1701:1728 the engineered chassis cells 1701:1728 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 3 46 theme Escherichia 640:650 arg1 strain 657:662 a glycol-engineered Escherichia coli strain 620:662 a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome 620:735 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 1 47 theme Glycan 215:220 arg1 Technology 231:240 Protein Glycan Coupling Technology 207:240 Protein Glycan Coupling Technology (PGCT) 207:247 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 1 47 theme Glycan 215:220 arg1 PGCT 243:246 PGCT 243:246 PGCT 243:246 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 6 48 dep Klebsiella 1335:1344 arg1 pneumoniae 1346:1355 pneumoniae 1346:1355 pneumoniae 1346:1355 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 4 49 with glycoproteins 779:791 arg1 polysaccharides 808:822 antigenic polysaccharides 798:822 antigenic polysaccharides produced by our bacterial chassis 798:856 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 6 50 theme Klebsiella 1335:1344 arg1 KPO1-VLP 1383:1390 KPO1-VLP 1383:1390 KPO1-VLP 1383:1390 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 6 50 theme Klebsiella 1335:1344 arg1 nanovaccine 1370:1380 an effective Klebsiella pneumoniae O1 conjugate nanovaccine 1322:1380 an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP) 1322:1391 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 3 51 theme key 679:681 arg1 PglL 706:709 PglL 706:709 PglL 706:709 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 51 theme key 679:681 arg1 SC4573 695:700 SC4573 695:700 SC4573 695:700 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 51 theme key 679:681 arg1 components 683:692 these two key components 669:692 these two key components (SC4573 and PglL) integrated in its genome 669:735 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 52 used used 548:551 arg2 protein 520:526 a generic recombinant protein 498:526 a generic recombinant protein (SpyCather4573) 498:542 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 52 used used 548:551 arg2 protein 569:575 the acceptor protein 556:575 the acceptor protein for O-linked glycosyltransferase PglL 556:613 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 52 used used 548:551 arg2 SpyCather4573 529:541 SpyCather4573 529:541 SpyCather4573 529:541 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 4 53 gly glycoproteins 779:791 arg1 glycoproteins 779:791 The targeted glycoproteins 766:791 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis 766:856 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 4 54 dep exposed 925:931 arg1 form 952:955 form 952:955 exposed SpyTag in vitro to form conjugate nanovaccines 925:978 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 4 54 dep exposed 925:931 arg1 SpyTag 933:938 SpyTag 933:938 SpyTag 933:938 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 4 54 dep exposed 925:931 arg1 surface 917:923 surface 917:923 surface exposed SpyTag in vitro to form conjugate nanovaccines 917:978 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 6 55 theme effective 1325:1333 arg1 KPO1-VLP 1383:1390 KPO1-VLP 1383:1390 KPO1-VLP 1383:1390 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 6 55 theme effective 1325:1333 arg1 nanovaccine 1370:1380 an effective Klebsiella pneumoniae O1 conjugate nanovaccine 1322:1380 an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP) 1322:1391 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 7 56 theme bacterial 1597:1605 arg1 preparation 1628:1638 bacterial glycoprotein vaccine preparation 1597:1638 bacterial glycoprotein vaccine preparation 1597:1638 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 7 57 theme wide 1741:1744 arg1 range 1746:1750 a wide range 1739:1750 a wide range of applications for biosynthetic glycobiology research 1739:1805 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 0 58 theme nanovaccine 49:59 arg1 Preparation 0:10 Preparation 0:10 Preparation of a Klebsiella pneumoniae conjugate nanovaccine 0:59 Preparation of a Klebsiella pneumoniae conjugate nanovaccine using glycol-engineered Escherichia coli. 37149632 5 59 theme glycoproteins 1192:1204 arg1 expression 1178:1187 the expression 1174:1187 the expression of glycoproteins 1174:1204 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 3 60 theme glycol-engineered 622:638 arg1 strain 657:662 a glycol-engineered Escherichia coli strain 620:662 a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome 620:735 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 1 61 theme coli 148:151 arg1 strains 125:131 BACKGROUND Engineered strains 103:131 BACKGROUND Engineered strains of Escherichia coli 103:151 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 5 62 theme cluster 1050:1056 arg1 experiments 1067:1077 gene cluster deletion experiments 1045:1077 gene cluster deletion experiments 1045:1077 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 4 63 theme conjugate 957:965 arg1 nanovaccines 967:978 conjugate nanovaccines 957:978 conjugate nanovaccines 957:978 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 2 64 theme vaccine 285:291 arg1 arena 305:309 the vaccine development arena 281:309 the vaccine development arena 281:309 Nanovaccines have also entered the vaccine development arena with advances in nanotechnology and have been significantly developed, but chassis cells for conjugate nanovaccines have not been reported. 37149632 0 65 dep Klebsiella 17:26 arg1 pneumoniae 28:37 pneumoniae 28:37 pneumoniae 28:37 Preparation of a Klebsiella pneumoniae conjugate nanovaccine using glycol-engineered Escherichia coli. 37149632 5 66 theme experiments 1067:1077 arg1 series 1035:1040 a series 1033:1040 a series of gene cluster deletion experiments 1033:1077 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 7 67 theme applications 1755:1766 arg1 range 1746:1750 a wide range 1739:1750 a wide range of applications for biosynthetic glycobiology research 1739:1805 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 2 68 theme development 293:303 arg1 arena 305:309 the vaccine development arena 281:309 the vaccine development arena 281:309 Nanovaccines have also entered the vaccine development arena with advances in nanotechnology and have been significantly developed, but chassis cells for conjugate nanovaccines have not been reported. 37149632 5 69 theme targeted 1010:1017 arg1 glycoprotein 1019:1030 the targeted glycoprotein 1006:1030 the targeted glycoprotein 1006:1030 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 6 70 dep 100 1475:1477 arg1 to 1472:1473 to 1472:1473 to 1472:1473 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 6 71 theme strain 1508:1513 arg1 challenge 1515:1523 virulent strain challenge 1499:1523 virulent strain challenge 1499:1523 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 2 72 from advances 316:323 arg1 nanotechnology 328:341 nanotechnology 328:341 nanotechnology 328:341 Nanovaccines have also entered the vaccine development arena with advances in nanotechnology and have been significantly developed, but chassis cells for conjugate nanovaccines have not been reported. 37149632 3 73 dep components 683:692 arg1 PglL 706:709 PglL 706:709 PglL 706:709 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 73 dep components 683:692 arg1 SC4573 695:700 SC4573 695:700 SC4573 695:700 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 73 dep components 683:692 arg1 components 683:692 these two key components 669:692 these two key components (SC4573 and PglL) integrated in its genome 669:735 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 74 with strain 657:662 arg1 PglL 706:709 PglL 706:709 PglL 706:709 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 74 with strain 657:662 arg1 SC4573 695:700 SC4573 695:700 SC4573 695:700 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 3 74 with strain 657:662 arg1 components 683:692 these two key components 669:692 these two key components (SC4573 and PglL) integrated in its genome 669:735 RESULTS To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. 37149632 6 75 theme triple 1445:1450 arg1 immunization 1452:1463 triple immunization 1445:1463 triple immunization 1445:1463 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 5 76 theme gene 1045:1048 arg1 experiments 1067:1077 gene cluster deletion experiments 1045:1077 gene cluster deletion experiments 1045:1077 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 1 77 theme Coupling 222:229 arg1 Technology 231:240 Protein Glycan Coupling Technology 207:240 Protein Glycan Coupling Technology (PGCT) 207:247 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 1 77 theme Coupling 222:229 arg1 PGCT 243:246 PGCT 243:246 PGCT 243:246 BACKGROUND Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). 37149632 7 78 theme reliable 1574:1581 arg1 framework 1583:1591 a convenient and reliable framework 1557:1591 a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile 1557:1669 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 7 78 theme reliable 1574:1581 arg1 flexible 1648:1655 flexible 1648:1655 flexible 1648:1655 CONCLUSIONS Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research. 37149632 6 79 theme antibody 1399:1406 arg1 titers 1408:1413 antibody titers 1399:1413 antibody titers between 4 and 5 (Log10) after triple immunization 1399:1463 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 37149632 5 80 theme gene 1151:1154 arg1 cluster 1156:1162 the yfdGHI gene cluster 1140:1162 the yfdGHI gene cluster 1140:1162 To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. 37149632 4 81 theme bacterial 840:848 arg1 chassis 850:856 our bacterial chassis 836:856 our bacterial chassis 836:856 The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. 37149632 6 82 dep protection 1480:1489 arg1 % 1478:1478 % 1478:1478 % 1478:1478 Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. 36865196 0 0 theme disease 108:114 arg1 mutations 116:124 Charcot-Marie-Tooth disease mutations 88:124 Charcot-Marie-Tooth disease mutations 88:124 O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations. 36865196 8 1 theme O-GlcNAcylation 1170:1184 arg1 effects 1159:1165 the effects 1155:1165 the effects of O-GlcNAcylation on NF assembly state 1155:1205 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 7 2 theme organelle 983:991 arg1 trafficking 993:1003 normal organelle trafficking 976:1003 normal organelle trafficking in primary neurons 976:1022 We further show that NF-L O-GlcNAcylation is required for normal organelle trafficking in primary neurons, underlining its functional significance. 36865196 0 3 theme Charcot-Marie-Tooth 88:106 arg1 mutations 116:124 Charcot-Marie-Tooth disease mutations 88:124 Charcot-Marie-Tooth disease mutations 88:124 O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations. 36865196 6 4 theme architecture 904:915 arg1 regulator 888:896 a general regulator 878:896 a general regulator of NF architecture 878:915 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 6 4 theme architecture 904:915 arg1 O-GlcNAc 866:873 O-GlcNAc 866:873 O-GlcNAc 866:873 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 8 5 theme dysregulated 1244:1255 arg1 O-GlcNAcylation 1257:1271 dysregulated O-GlcNAcylation 1244:1271 dysregulated O-GlcNAcylation 1244:1271 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 1 6 theme neuronal 179:186 arg1 morphology 188:197 morphology 188:197 morphology 188:197 The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. 36865196 5 7 theme assembly 706:713 arg1 state 715:719 NF assembly state 703:719 NF assembly state 703:719 We identify five NF-L O-GlcNAc sites and show that they regulate NF assembly state. 36865196 6 8 theme NF 901:902 arg1 architecture 904:915 NF architecture 901:915 NF architecture 901:915 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 2 9 theme CMT 354:356 arg1 disease 359:365 Charcot-Marie-Tooth (CMT) disease 333:365 Charcot-Marie-Tooth (CMT) disease 333:365 In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. 36865196 9 10 theme NF-L 1373:1376 arg1 assembly 1378:1385 NF-L assembly 1373:1385 NF-L assembly 1373:1385 Our results demonstrate that site-specific glycosylation regulates NF-L assembly and function, and aberrant NF O-GlcNAcylation may contribute to CMT and other neurodegenerative disorders. 36865196 5 11 theme NF-L 655:658 arg1 sites 669:673 five NF-L O-GlcNAc sites 650:673 five NF-L O-GlcNAc sites 650:673 We identify five NF-L O-GlcNAc sites and show that they regulate NF assembly state. 36865196 3 12 theme assembly 417:424 arg1 state 426:430 NF assembly state 414:430 NF assembly state 414:430 NFs are highly dynamic, and the regulation of NF assembly state is incompletely understood. 36865196 8 13 theme assembly 1192:1199 arg1 state 1201:1205 NF assembly state 1189:1205 NF assembly state 1189:1205 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 6 14 theme general 880:886 arg1 regulator 888:896 a general regulator 878:896 a general regulator of NF architecture 878:915 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 6 14 theme general 880:886 arg1 O-GlcNAc 866:873 O-GlcNAc 866:873 O-GlcNAc 866:873 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 2 15 theme NF 283:284 arg1 assembly 286:293 NF assembly 283:293 NF assembly 283:293 In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. 36865196 3 16 theme state 426:430 arg1 regulation 400:409 the regulation 396:409 the regulation of NF assembly state 396:430 NFs are highly dynamic, and the regulation of NF assembly state is incompletely understood. 36865196 4 17 theme O-linked-β- 543:553 arg1 O-GlcNAc 577:584 O-GlcNAc 577:584 O-GlcNAc 577:584 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 4 17 theme O-linked-β- 543:553 arg1 -acetylglucosamine 557:574 O-linked-β- N -acetylglucosamine 543:574 O-linked-β- N -acetylglucosamine (O-GlcNAc) 543:585 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 4 17 theme O-linked-β- 543:553 arg1 form 601:604 a ubiquitous form 588:604 a ubiquitous form of intracellular glycosylation 588:635 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 8 18 theme CMT-causative 1083:1095 arg1 mutants 1102:1108 several CMT-causative NF-L mutants 1075:1108 several CMT-causative NF-L mutants 1075:1108 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 7 19 theme NF-L 939:942 arg1 O-GlcNAcylation 944:958 NF-L O-GlcNAcylation 939:958 NF-L O-GlcNAcylation 939:958 We further show that NF-L O-GlcNAcylation is required for normal organelle trafficking in primary neurons, underlining its functional significance. 36865196 7 20 from trafficking 993:1003 arg1 neurons 1016:1022 primary neurons 1008:1022 primary neurons 1008:1022 We further show that NF-L O-GlcNAcylation is required for normal organelle trafficking in primary neurons, underlining its functional significance. 36865196 8 21 theme several 1075:1081 arg1 mutants 1102:1108 several CMT-causative NF-L mutants 1075:1108 several CMT-causative NF-L mutants 1075:1108 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 6 22 theme protein-protein 771:785 arg1 interactions 787:798 O-GlcNAc-mediated protein-protein interactions 753:798 O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin 753:849 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 3 23 theme NF 414:415 arg1 state 426:430 NF assembly state 414:430 NF assembly state 414:430 NFs are highly dynamic, and the regulation of NF assembly state is incompletely understood. 36865196 4 24 mod modified 500:507 arg3 -acetylglucosamine 557:574 O-linked-β- N -acetylglucosamine 543:574 O-linked-β- N -acetylglucosamine (O-GlcNAc) 543:585 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 4 24 mod modified 500:507 arg3 form 601:604 a ubiquitous form 588:604 a ubiquitous form of intracellular glycosylation 588:635 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 4 24 mod modified 500:507 arg3 O-GlcNAc 577:584 O-GlcNAc 577:584 O-GlcNAc 577:584 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 4 24 mod modified 500:507 arg1 NF-L 492:495 human NF-L 486:495 human NF-L 486:495 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 6 25 theme O-GlcNAc-mediated 753:769 arg1 interactions 787:798 O-GlcNAc-mediated protein-protein interactions 753:798 O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin 753:849 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 8 26 theme potential 1221:1229 arg1 link 1231:1234 a potential link 1219:1234 a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation 1219:1303 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 4 27 theme intracellular 609:621 arg1 glycosylation 623:635 intracellular glycosylation 609:635 intracellular glycosylation 609:635 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 0 28 theme neurofilament-light 26:44 arg1 assembly 46:53 neurofilament-light assembly 26:53 neurofilament-light assembly 26:53 O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations. 36865196 4 29 theme N 555:555 arg1 O-GlcNAc 577:584 O-GlcNAc 577:584 O-GlcNAc 577:584 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 4 29 theme N 555:555 arg1 -acetylglucosamine 557:574 O-linked-β- N -acetylglucosamine 543:574 O-linked-β- N -acetylglucosamine (O-GlcNAc) 543:585 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 4 29 theme N 555:555 arg1 form 601:604 a ubiquitous form 588:604 a ubiquitous form of intracellular glycosylation 588:635 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 8 30 theme NF-L 1097:1100 arg1 mutants 1102:1108 several CMT-causative NF-L mutants 1075:1108 several CMT-causative NF-L mutants 1075:1108 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 1 31 theme neurofilament 131:143 arg1 critical 166:173 critical 166:173 critical 166:173 The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. 36865196 1 31 theme neurofilament 131:143 arg1 cytoskeleton 150:161 The neurofilament (NF) cytoskeleton 127:161 The neurofilament (NF) cytoskeleton 127:161 The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. 36865196 2 32 theme Charcot-Marie-Tooth 333:351 arg1 disease 359:365 Charcot-Marie-Tooth (CMT) disease 333:365 Charcot-Marie-Tooth (CMT) disease 333:365 In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. 36865196 8 33 theme perturbed 1118:1126 arg1 levels 1137:1142 perturbed O-GlcNAc levels 1118:1142 perturbed O-GlcNAc levels 1118:1142 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 9 34 theme site-specific 1335:1347 arg1 glycosylation 1349:1361 site-specific glycosylation 1335:1361 site-specific glycosylation 1335:1361 Our results demonstrate that site-specific glycosylation regulates NF-L assembly and function, and aberrant NF O-GlcNAcylation may contribute to CMT and other neurodegenerative disorders. 36865196 8 35 theme NF 1290:1291 arg1 aggregation 1293:1303 pathological NF aggregation 1277:1303 pathological NF aggregation 1277:1303 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 9 36 theme aberrant 1405:1412 arg1 O-GlcNAcylation 1417:1431 aberrant NF O-GlcNAcylation 1405:1431 aberrant NF O-GlcNAcylation 1405:1431 Our results demonstrate that site-specific glycosylation regulates NF-L assembly and function, and aberrant NF O-GlcNAcylation may contribute to CMT and other neurodegenerative disorders. 36865196 8 37 theme pathological 1277:1288 arg1 aggregation 1293:1303 pathological NF aggregation 1277:1303 pathological NF aggregation 1277:1303 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 5 38 theme NF 703:704 arg1 state 715:719 NF assembly state 703:719 NF assembly state 703:719 We identify five NF-L O-GlcNAc sites and show that they regulate NF assembly state. 36865196 8 39 from effects 1159:1165 arg1 state 1201:1205 NF assembly state 1189:1205 NF assembly state 1189:1205 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 2 40 theme NF-L 253:256 arg1 subunit 259:265 the neurofilament-light (NF-L) subunit 228:265 the neurofilament-light (NF-L) subunit 228:265 In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. 36865196 4 41 theme glycosylation 623:635 arg1 -acetylglucosamine 557:574 O-linked-β- N -acetylglucosamine 543:574 O-linked-β- N -acetylglucosamine (O-GlcNAc) 543:585 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 4 41 theme glycosylation 623:635 arg1 form 601:604 a ubiquitous form 588:604 a ubiquitous form of intracellular glycosylation 588:635 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 8 42 theme NF 1189:1190 arg1 state 1201:1205 NF assembly state 1189:1205 NF assembly state 1189:1205 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 5 43 theme O-GlcNAc 660:667 arg1 sites 669:673 five NF-L O-GlcNAc sites 650:673 five NF-L O-GlcNAc sites 650:673 We identify five NF-L O-GlcNAc sites and show that they regulate NF assembly state. 36865196 6 44 with interactions 787:798 arg1 α-internexin 838:849 the NF component α-internexin 821:849 the NF component α-internexin 821:849 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 6 44 with interactions 787:798 arg1 itself 805:810 itself 805:810 itself 805:810 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 4 45 theme nutrient-sensitive 514:531 arg1 manner 533:538 a nutrient-sensitive manner 512:538 a nutrient-sensitive manner 512:538 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 8 46 theme O-GlcNAc 1128:1135 arg1 levels 1137:1142 perturbed O-GlcNAc levels 1118:1142 perturbed O-GlcNAc levels 1118:1142 Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. 36865196 2 47 theme neurofilament-light 232:250 arg1 subunit 259:265 the neurofilament-light (NF-L) subunit 228:265 the neurofilament-light (NF-L) subunit 228:265 In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. 36865196 7 48 theme primary 1008:1014 arg1 neurons 1016:1022 primary neurons 1008:1022 primary neurons 1008:1022 We further show that NF-L O-GlcNAcylation is required for normal organelle trafficking in primary neurons, underlining its functional significance. 36865196 1 49 theme NF 146:147 arg1 critical 166:173 critical 166:173 critical 166:173 The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. 36865196 1 49 theme NF 146:147 arg1 cytoskeleton 150:161 The neurofilament (NF) cytoskeleton 127:161 The neurofilament (NF) cytoskeleton 127:161 The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. 36865196 9 50 theme NF 1414:1415 arg1 O-GlcNAcylation 1417:1431 aberrant NF O-GlcNAcylation 1405:1431 aberrant NF O-GlcNAcylation 1405:1431 Our results demonstrate that site-specific glycosylation regulates NF-L assembly and function, and aberrant NF O-GlcNAcylation may contribute to CMT and other neurodegenerative disorders. 36865196 7 51 theme functional 1041:1050 arg1 significance 1052:1063 its functional significance 1037:1063 its functional significance 1037:1063 We further show that NF-L O-GlcNAcylation is required for normal organelle trafficking in primary neurons, underlining its functional significance. 36865196 6 52 theme component 828:836 arg1 α-internexin 838:849 the NF component α-internexin 821:849 the NF component α-internexin 821:849 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 6 53 theme NF 825:826 arg1 α-internexin 838:849 the NF component α-internexin 821:849 the NF component α-internexin 821:849 Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. 36865196 9 54 theme other 1459:1463 arg1 disorders 1483:1491 other neurodegenerative disorders 1459:1491 other neurodegenerative disorders 1459:1491 Our results demonstrate that site-specific glycosylation regulates NF-L assembly and function, and aberrant NF O-GlcNAcylation may contribute to CMT and other neurodegenerative disorders. 36865196 4 55 theme human 486:490 arg1 NF-L 492:495 human NF-L 486:495 human NF-L 486:495 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 9 56 theme neurodegenerative 1465:1481 arg1 disorders 1483:1491 other neurodegenerative disorders 1459:1491 other neurodegenerative disorders 1459:1491 Our results demonstrate that site-specific glycosylation regulates NF-L assembly and function, and aberrant NF O-GlcNAcylation may contribute to CMT and other neurodegenerative disorders. 36865196 7 57 theme normal 976:981 arg1 trafficking 993:1003 normal organelle trafficking 976:1003 normal organelle trafficking in primary neurons 976:1022 We further show that NF-L O-GlcNAcylation is required for normal organelle trafficking in primary neurons, underlining its functional significance. 36865196 2 58 theme disease 359:365 arg1 subtypes 321:328 subtypes 321:328 subtypes of Charcot-Marie-Tooth (CMT) disease 321:365 In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. 36865196 4 59 theme ubiquitous 590:599 arg1 -acetylglucosamine 557:574 O-linked-β- N -acetylglucosamine 543:574 O-linked-β- N -acetylglucosamine (O-GlcNAc) 543:585 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 36865196 4 59 theme ubiquitous 590:599 arg1 form 601:604 a ubiquitous form 588:604 a ubiquitous form of intracellular glycosylation 588:635 Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. 37286543 4 0 theme biofilm 922:928 arg1 matrix 944:949 the biofilm extracellular matrix 918:949 the biofilm extracellular matrix 918:949 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 2 1 from contamination 580:592 arg1 environments 613:624 food-processing environments 597:624 food-processing environments 597:624 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 6 2 theme genes 1372:1376 arg1 expression 1358:1367 the expression 1354:1367 the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49) 1354:1603 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 4 3 theme matrix 944:949 arg1 composition 903:913 the composition 899:913 the composition of the biofilm extracellular matrix 899:949 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 7 4 theme mutant 1830:1835 arg1 cells 1811:1815 human cells 1805:1815 human cells of the ΔpnpA mutant 1805:1835 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 8 5 theme important 1888:1896 arg1 regulator 1919:1927 an important post-transcriptional regulator 1885:1927 an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria 1885:2007 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 8 5 theme important 1888:1896 arg1 PNPase 1875:1880 PNPase 1875:1880 PNPase 1875:1880 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 1 6 theme immune 267:272 arg1 defences 274:281 immune defences 267:281 immune defences 267:281 Biofilms provide an environment that protects microorganisms from external stresses such as nutrient deprivation, antibiotic treatments, and immune defences, thereby creating favorable conditions for bacterial survival and pathogenesis. 37286543 6 7 theme biofilms 1231:1238 arg1 analysis 1191:1198 Transcriptomic analysis 1176:1198 Transcriptomic analysis of wild-type and PNPase mutant biofilms 1176:1238 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 6 8 theme quorum 1565:1570 arg1 system 1585:1590 the Agr quorum sensing-like system 1557:1590 the Agr quorum sensing-like system (lmo0048-49) 1557:1603 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 6 8 theme quorum 1565:1570 arg1 lmo0048-49 1593:1602 lmo0048-49 1593:1602 lmo0048-49 1593:1602 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 7 9 theme master 1663:1668 arg1 regulator 1670:1678 the master regulator 1659:1678 the master regulator of virulence PrfA and PrfA-regulated genes 1659:1721 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 0 10 theme cells 119:123 arg1 invasion 102:109 invasion 102:109 invasion of host cells 102:123 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 3 11 theme PNPase 631:636 arg1 strain 645:650 The PNPase mutant strain 627:650 The PNPase mutant strain 627:650 The PNPase mutant strain produces less biofilm biomass and exhibits an altered biofilm morphology that is more susceptible to antibiotic treatment. 37286543 2 12 theme food-processing 597:611 arg1 environments 613:624 food-processing environments 597:624 food-processing environments 597:624 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 6 13 theme biofilm 1309:1315 arg1 formation 1317:1325 biofilm formation 1309:1325 biofilm formation 1309:1325 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 5 14 theme complex 1080:1086 arg1 red-phenanthroline 1098:1115 the fluorescent complex ruthenium red-phenanthroline 1064:1115 the fluorescent complex ruthenium red-phenanthroline 1064:1115 Noteworthy, we have adapted the use of the fluorescent complex ruthenium red-phenanthroline for the detection of polysaccharides in Listeria biofilms. 37286543 7 15 theme reduced 1768:1774 arg1 internalization 1786:1800 the reduced bacterial internalization 1764:1800 the reduced bacterial internalization in human cells of the ΔpnpA mutant 1764:1835 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 7 16 theme mRNA 1644:1647 arg1 levels 1649:1654 mRNA levels 1644:1654 mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes 1644:1721 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 8 17 theme Gram-positive 1986:1998 arg1 bacteria 2000:2007 Gram-positive bacteria 1986:2007 Gram-positive bacteria 1986:2007 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 5 18 theme red-phenanthroline 1098:1115 arg1 use 1057:1059 the use 1053:1059 the use of the fluorescent complex ruthenium red-phenanthroline for the detection of polysaccharides in Listeria biofilms 1053:1173 Noteworthy, we have adapted the use of the fluorescent complex ruthenium red-phenanthroline for the detection of polysaccharides in Listeria biofilms. 37286543 2 19 theme human 512:516 arg1 monocytogenes 536:548 the human pathogen Listeria monocytogenes 508:548 the human pathogen Listeria monocytogenes 508:548 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 6 20 theme regulatory 1273:1282 arg1 pathways 1284:1291 many regulatory pathways 1268:1291 many regulatory pathways associated with biofilm formation 1268:1325 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 0 21 theme biofilm 46:52 arg1 formation 54:62 biofilm formation 46:62 biofilm formation 46:62 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 6 22 dep lmo0096 1429:1435 arg1 e.g. 1423:1426 e.g. 1423:1426 e.g. 1423:1426 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 4 23 theme DNA 1008:1010 arg1 levels 974:979 the levels 970:979 the levels of proteins, extracellular DNA, and sugars 970:1022 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 2 24 theme Listeria 527:534 arg1 monocytogenes 536:548 the human pathogen Listeria monocytogenes 508:548 the human pathogen Listeria monocytogenes 508:548 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 0 25 from regulator 33:41 arg1 monocytogenes 76:88 Listeria monocytogenes 67:88 Listeria monocytogenes 67:88 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 5 26 from detection 1125:1133 arg1 biofilms 1166:1173 Listeria biofilms 1157:1173 Listeria biofilms 1157:1173 Noteworthy, we have adapted the use of the fluorescent complex ruthenium red-phenanthroline for the detection of polysaccharides in Listeria biofilms. 37286543 6 27 theme acids 1485:1489 arg1 expression 1358:1367 the expression 1354:1367 the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49) 1354:1603 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 7 28 theme genes 1717:1721 arg1 regulator 1670:1678 the master regulator 1659:1678 the master regulator of virulence PrfA and PrfA-regulated genes 1659:1721 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 4 29 theme biochemical 783:793 arg1 assays 795:800 biochemical assays 783:800 biochemical assays 783:800 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 2 30 theme RNA-binding 385:395 arg1 protein 397:403 the RNA-binding protein 381:403 the RNA-binding protein 381:403 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 30 theme RNA-binding 385:395 arg1 regulator 474:482 a positive regulator 463:482 a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes 463:548 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 30 theme RNA-binding 385:395 arg1 phosphorylase 437:449 ribonuclease polynucleotide phosphorylase 409:449 ribonuclease polynucleotide phosphorylase (PNPase) 409:458 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 8 31 theme critical 2063:2070 arg1 players 2072:2078 critical players 2063:2078 critical players in pathogenicity 2063:2095 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 8 31 theme critical 2063:2070 arg1 role 2038:2041 the expanding role 2024:2041 the expanding role of ribonucleases 2024:2058 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 7 32 theme virulence 1683:1691 arg1 PrfA 1693:1696 virulence PrfA 1683:1696 virulence PrfA 1683:1696 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 2 33 theme biofilm 487:493 arg1 formation 495:503 biofilm formation 487:503 biofilm formation 487:503 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 34 theme polynucleotide 422:435 arg1 protein 397:403 the RNA-binding protein 381:403 the RNA-binding protein 381:403 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 34 theme polynucleotide 422:435 arg1 regulator 474:482 a positive regulator 463:482 a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes 463:548 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 34 theme polynucleotide 422:435 arg1 PNPase 452:457 PNPase 452:457 PNPase 452:457 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 34 theme polynucleotide 422:435 arg1 phosphorylase 437:449 ribonuclease polynucleotide phosphorylase 409:449 ribonuclease polynucleotide phosphorylase (PNPase) 409:458 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 6 35 theme amino 1479:1483 arg1 acids 1485:1489 amino acids 1479:1489 amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) 1479:1548 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 1 36 theme favorable 301:309 arg1 conditions 311:320 favorable conditions 301:320 favorable conditions for bacterial survival and pathogenesis 301:360 Biofilms provide an environment that protects microorganisms from external stresses such as nutrient deprivation, antibiotic treatments, and immune defences, thereby creating favorable conditions for bacterial survival and pathogenesis. 37286543 8 37 theme ribonucleases 2046:2058 arg1 players 2072:2078 critical players 2063:2078 critical players in pathogenicity 2063:2095 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 8 37 theme ribonucleases 2046:2058 arg1 role 2038:2041 the expanding role 2024:2041 the expanding role of ribonucleases 2024:2058 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 5 38 theme fluorescent 1068:1078 arg1 red-phenanthroline 1098:1115 the fluorescent complex ruthenium red-phenanthroline 1064:1115 the fluorescent complex ruthenium red-phenanthroline 1064:1115 Noteworthy, we have adapted the use of the fluorescent complex ruthenium red-phenanthroline for the detection of polysaccharides in Listeria biofilms. 37286543 1 39 theme nutrient 218:225 arg1 deprivation 227:237 nutrient deprivation 218:237 nutrient deprivation 218:237 Biofilms provide an environment that protects microorganisms from external stresses such as nutrient deprivation, antibiotic treatments, and immune defences, thereby creating favorable conditions for bacterial survival and pathogenesis. 37286543 6 40 theme Transcriptomic 1176:1189 arg1 analysis 1191:1198 Transcriptomic analysis 1176:1198 Transcriptomic analysis of wild-type and PNPase mutant biofilms 1176:1238 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 3 41 theme altered 698:704 arg1 susceptible 738:748 susceptible 738:748 susceptible 738:748 The PNPase mutant strain produces less biofilm biomass and exhibits an altered biofilm morphology that is more susceptible to antibiotic treatment. 37286543 3 41 theme altered 698:704 arg1 morphology 714:723 an altered biofilm morphology 695:723 an altered biofilm morphology that is more susceptible to antibiotic treatment 695:772 The PNPase mutant strain produces less biofilm biomass and exhibits an altered biofilm morphology that is more susceptible to antibiotic treatment. 37286543 6 42 theme biosynthetic 1528:1539 arg1 enzymes 1541:1547 biosynthetic enzymes 1528:1547 biosynthetic enzymes 1528:1547 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 6 43 theme PTS 1459:1461 arg1 components 1463:1472 PTS components 1459:1472 PTS components 1459:1472 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 7 44 theme ΔpnpA 1824:1828 arg1 mutant 1830:1835 the ΔpnpA mutant 1820:1835 the ΔpnpA mutant 1820:1835 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 8 45 theme post-transcriptional 1898:1917 arg1 regulator 1919:1927 an important post-transcriptional regulator 1885:1927 an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria 1885:2007 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 8 45 theme post-transcriptional 1898:1917 arg1 PNPase 1875:1880 PNPase 1875:1880 PNPase 1875:1880 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 4 46 theme extracellular 930:942 arg1 matrix 944:949 the biofilm extracellular matrix 918:949 the biofilm extracellular matrix 918:949 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 6 47 theme wild-type 1203:1211 arg1 biofilms 1231:1238 wild-type and PNPase mutant biofilms 1203:1238 wild-type and PNPase mutant biofilms 1203:1238 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 7 48 theme human 1805:1809 arg1 cells 1811:1815 human cells 1805:1815 human cells of the ΔpnpA mutant 1805:1835 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 3 49 theme antibiotic 753:762 arg1 treatment 764:772 antibiotic treatment 753:772 antibiotic treatment 753:772 The PNPase mutant strain produces less biofilm biomass and exhibits an altered biofilm morphology that is more susceptible to antibiotic treatment. 37286543 6 50 theme sensing-like 1572:1583 arg1 system 1585:1590 the Agr quorum sensing-like system 1557:1590 the Agr quorum sensing-like system (lmo0048-49) 1557:1603 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 6 50 theme sensing-like 1572:1583 arg1 lmo0048-49 1593:1602 lmo0048-49 1593:1602 lmo0048-49 1593:1602 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 7 51 theme regulator 1670:1678 arg1 levels 1649:1654 mRNA levels 1644:1654 mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes 1644:1721 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 4 52 theme composition 903:913 arg1 PNPase 850:855 PNPase 850:855 PNPase 850:855 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 4 52 theme composition 903:913 arg1 regulator 886:894 a previously unrecognized regulator 860:894 a previously unrecognized regulator of the composition of the biofilm extracellular matrix 860:949 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 6 53 theme mutant 1224:1229 arg1 biofilms 1231:1238 wild-type and PNPase mutant biofilms 1203:1238 wild-type and PNPase mutant biofilms 1203:1238 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 0 54 theme host 114:117 arg1 cells 119:123 host cells 114:123 host cells 114:123 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 6 55 theme Agr 1561:1563 arg1 system 1585:1590 the Agr quorum sensing-like system 1557:1590 the Agr quorum sensing-like system (lmo0048-49) 1557:1603 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 6 55 theme Agr 1561:1563 arg1 lmo0048-49 1593:1602 lmo0048-49 1593:1602 lmo0048-49 1593:1602 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 1 56 theme external 192:199 arg1 stresses 201:208 external stresses 192:208 external stresses such as nutrient deprivation, antibiotic treatments, and immune defences 192:281 Biofilms provide an environment that protects microorganisms from external stresses such as nutrient deprivation, antibiotic treatments, and immune defences, thereby creating favorable conditions for bacterial survival and pathogenesis. 37286543 1 56 theme external 192:199 arg1 defences 274:281 immune defences 267:281 immune defences 267:281 Biofilms provide an environment that protects microorganisms from external stresses such as nutrient deprivation, antibiotic treatments, and immune defences, thereby creating favorable conditions for bacterial survival and pathogenesis. 37286543 1 56 theme external 192:199 arg1 deprivation 227:237 nutrient deprivation 218:237 nutrient deprivation 218:237 Biofilms provide an environment that protects microorganisms from external stresses such as nutrient deprivation, antibiotic treatments, and immune defences, thereby creating favorable conditions for bacterial survival and pathogenesis. 37286543 1 56 theme external 192:199 arg1 treatments 251:260 antibiotic treatments 240:260 antibiotic treatments 240:260 Biofilms provide an environment that protects microorganisms from external stresses such as nutrient deprivation, antibiotic treatments, and immune defences, thereby creating favorable conditions for bacterial survival and pathogenesis. 37286543 8 57 theme biofilm 1965:1971 arg1 lifestyle 1973:1981 the biofilm lifestyle 1961:1981 the biofilm lifestyle of Gram-positive bacteria 1961:2007 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 4 58 theme proteins 984:991 arg1 levels 974:979 the levels 970:979 the levels of proteins, extracellular DNA, and sugars 970:1022 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 5 59 theme polysaccharides 1138:1152 arg1 detection 1125:1133 the detection 1121:1133 the detection of polysaccharides in Listeria biofilms 1121:1173 Noteworthy, we have adapted the use of the fluorescent complex ruthenium red-phenanthroline for the detection of polysaccharides in Listeria biofilms. 37286543 8 60 theme bacteria 2000:2007 arg1 lifestyle 1973:1981 the biofilm lifestyle 1961:1981 the biofilm lifestyle of Gram-positive bacteria 1961:2007 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 5 61 theme ruthenium 1088:1096 arg1 red-phenanthroline 1098:1115 the fluorescent complex ruthenium red-phenanthroline 1064:1115 the fluorescent complex ruthenium red-phenanthroline 1064:1115 Noteworthy, we have adapted the use of the fluorescent complex ruthenium red-phenanthroline for the detection of polysaccharides in Listeria biofilms. 37286543 7 62 theme bacterial 1776:1784 arg1 internalization 1786:1800 the reduced bacterial internalization 1764:1800 the reduced bacterial internalization in human cells of the ΔpnpA mutant 1764:1835 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 2 63 theme food 575:578 arg1 contamination 580:592 food contamination 575:592 food contamination in food-processing environments 575:624 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 0 64 theme formation 54:62 arg1 PNPase 17:22 The ribonuclease PNPase 0:22 The ribonuclease PNPase 0:22 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 0 64 theme formation 54:62 arg1 regulator 33:41 a key regulator 27:41 a key regulator of biofilm formation in Listeria monocytogenes 27:88 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 3 65 theme mutant 638:643 arg1 strain 645:650 The PNPase mutant strain 627:650 The PNPase mutant strain 627:650 The PNPase mutant strain produces less biofilm biomass and exhibits an altered biofilm morphology that is more susceptible to antibiotic treatment. 37286543 4 66 theme sugars 1017:1022 arg1 levels 974:979 the levels 970:979 the levels of proteins, extracellular DNA, and sugars 970:1022 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 6 67 theme many 1268:1271 arg1 pathways 1284:1291 many regulatory pathways 1268:1291 many regulatory pathways associated with biofilm formation 1268:1325 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 0 68 theme Listeria 67:74 arg1 monocytogenes 76:88 Listeria monocytogenes 67:88 Listeria monocytogenes 67:88 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 2 69 theme formation 495:503 arg1 protein 397:403 the RNA-binding protein 381:403 the RNA-binding protein 381:403 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 69 theme formation 495:503 arg1 regulator 474:482 a positive regulator 463:482 a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes 463:548 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 69 theme formation 495:503 arg1 phosphorylase 437:449 ribonuclease polynucleotide phosphorylase 409:449 ribonuclease polynucleotide phosphorylase (PNPase) 409:458 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 69 theme formation 495:503 arg1 major 553:557 major 553:557 major 553:557 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 8 70 from players 2072:2078 arg1 pathogenicity 2083:2095 pathogenicity 2083:2095 pathogenicity 2083:2095 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 4 71 theme extracellular 994:1006 arg1 DNA 1008:1010 extracellular DNA 994:1010 extracellular DNA 994:1010 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 2 72 from regulator 474:482 arg1 monocytogenes 536:548 the human pathogen Listeria monocytogenes 508:548 the human pathogen Listeria monocytogenes 508:548 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 4 73 theme microscopical 806:818 arg1 analysis 820:827 microscopical analysis 806:827 microscopical analysis 806:827 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 5 74 theme Listeria 1157:1164 arg1 biofilms 1166:1173 Listeria biofilms 1157:1173 Listeria biofilms 1157:1173 Noteworthy, we have adapted the use of the fluorescent complex ruthenium red-phenanthroline for the detection of polysaccharides in Listeria biofilms. 37286543 2 75 theme pathogen 518:525 arg1 monocytogenes 536:548 the human pathogen Listeria monocytogenes 508:548 the human pathogen Listeria monocytogenes 508:548 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 0 76 theme ribonuclease 4:15 arg1 PNPase 17:22 The ribonuclease PNPase 0:22 The ribonuclease PNPase 0:22 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 0 76 theme ribonuclease 4:15 arg1 regulator 33:41 a key regulator 27:41 a key regulator of biofilm formation in Listeria monocytogenes 27:88 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 7 77 theme PrfA-regulated 1702:1715 arg1 genes 1717:1721 PrfA-regulated genes 1702:1721 PrfA-regulated genes 1702:1721 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 0 78 theme key 29:31 arg1 PNPase 17:22 The ribonuclease PNPase 0:22 The ribonuclease PNPase 0:22 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 0 78 theme key 29:31 arg1 regulator 33:41 a key regulator 27:41 a key regulator of biofilm formation in Listeria monocytogenes 27:88 The ribonuclease PNPase is a key regulator of biofilm formation in Listeria monocytogenes and affects invasion of host cells. 37286543 7 79 theme PrfA 1693:1696 arg1 regulator 1670:1678 the master regulator 1659:1678 the master regulator of virulence PrfA and PrfA-regulated genes 1659:1721 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 3 80 theme biofilm 666:672 arg1 biomass 674:680 less biofilm biomass 661:680 less biofilm biomass 661:680 The PNPase mutant strain produces less biofilm biomass and exhibits an altered biofilm morphology that is more susceptible to antibiotic treatment. 37286543 8 81 theme expanding 2028:2036 arg1 players 2072:2078 critical players 2063:2078 critical players in pathogenicity 2063:2095 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 8 81 theme expanding 2028:2036 arg1 role 2038:2041 the expanding role 2024:2041 the expanding role of ribonucleases 2024:2058 Overall, this work demonstrates that PNPase is an important post-transcriptional regulator for virulence and adaptation to the biofilm lifestyle of Gram-positive bacteria and highlights the expanding role of ribonucleases as critical players in pathogenicity. 37286543 2 82 theme ribonuclease 409:420 arg1 protein 397:403 the RNA-binding protein 381:403 the RNA-binding protein 381:403 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 82 theme ribonuclease 409:420 arg1 regulator 474:482 a positive regulator 463:482 a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes 463:548 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 82 theme ribonuclease 409:420 arg1 PNPase 452:457 PNPase 452:457 PNPase 452:457 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 82 theme ribonuclease 409:420 arg1 phosphorylase 437:449 ribonuclease polynucleotide phosphorylase 409:449 ribonuclease polynucleotide phosphorylase (PNPase) 409:458 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 7 83 from internalization 1786:1800 arg1 cells 1811:1815 human cells 1805:1815 human cells of the ΔpnpA mutant 1805:1835 Moreover, we show that PNPase affects mRNA levels of the master regulator of virulence PrfA and PrfA-regulated genes, and these results could help to explain the reduced bacterial internalization in human cells of the ΔpnpA mutant. 37286543 2 84 theme positive 465:472 arg1 protein 397:403 the RNA-binding protein 381:403 the RNA-binding protein 381:403 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 84 theme positive 465:472 arg1 regulator 474:482 a positive regulator 463:482 a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes 463:548 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 84 theme positive 465:472 arg1 phosphorylase 437:449 ribonuclease polynucleotide phosphorylase 409:449 ribonuclease polynucleotide phosphorylase (PNPase) 409:458 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 2 84 theme positive 465:472 arg1 major 553:557 major 553:557 major 553:557 Here we show that the RNA-binding protein and ribonuclease polynucleotide phosphorylase (PNPase) is a positive regulator of biofilm formation in the human pathogen Listeria monocytogenes, a major responsible for food contamination in food-processing environments. 37286543 3 85 theme biofilm 706:712 arg1 susceptible 738:748 susceptible 738:748 susceptible 738:748 The PNPase mutant strain produces less biofilm biomass and exhibits an altered biofilm morphology that is more susceptible to antibiotic treatment. 37286543 3 85 theme biofilm 706:712 arg1 morphology 714:723 an altered biofilm morphology 695:723 an altered biofilm morphology that is more susceptible to antibiotic treatment 695:772 The PNPase mutant strain produces less biofilm biomass and exhibits an altered biofilm morphology that is more susceptible to antibiotic treatment. 37286543 4 86 theme unrecognized 873:884 arg1 PNPase 850:855 PNPase 850:855 PNPase 850:855 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 4 86 theme unrecognized 873:884 arg1 regulator 886:894 a previously unrecognized regulator 860:894 a previously unrecognized regulator of the composition of the biofilm extracellular matrix 860:949 Through biochemical assays and microscopical analysis, we demonstrate that PNPase is a previously unrecognized regulator of the composition of the biofilm extracellular matrix, greatly affecting the levels of proteins, extracellular DNA, and sugars. 37286543 1 87 theme bacterial 326:334 arg1 survival 336:343 bacterial survival 326:343 bacterial survival 326:343 Biofilms provide an environment that protects microorganisms from external stresses such as nutrient deprivation, antibiotic treatments, and immune defences, thereby creating favorable conditions for bacterial survival and pathogenesis. 37286543 6 88 dep lmo1984 1498:1504 arg1 e.g. 1492:1495 e.g. 1492:1495 e.g. 1492:1495 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 6 89 theme carbohydrates 1408:1420 arg1 metabolism 1394:1403 the metabolism 1390:1403 the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components) 1390:1473 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 6 90 from expression 1358:1367 arg1 system 1585:1590 the Agr quorum sensing-like system 1557:1590 the Agr quorum sensing-like system (lmo0048-49) 1557:1603 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 6 90 from expression 1358:1367 arg1 lmo0048-49 1593:1602 lmo0048-49 1593:1602 lmo0048-49 1593:1602 Transcriptomic analysis of wild-type and PNPase mutant biofilms reveals that PNPase impacts many regulatory pathways associated with biofilm formation, particularly by affecting the expression of genes involved in the metabolism of carbohydrates (e.g., lmo0096 and lmo0783, encoding PTS components), of amino acids (e.g., lmo1984 and lmo2006, encoding biosynthetic enzymes) and in the Agr quorum sensing-like system (lmo0048-49). 37286543 1 91 theme antibiotic 240:249 arg1 treatments 251:260 antibiotic treatments 240:260 antibiotic treatments 240:260 Biofilms provide an environment that protects microorganisms from external stresses such as nutrient deprivation, antibiotic treatments, and immune defences, thereby creating favorable conditions for bacterial survival and pathogenesis. 36854956 4 0 theme eDNA 805:808 arg1 Removal 794:800 Removal 794:800 Removal of eDNA, which was sensitive to treatment by DNase, 794:852 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 8 1 theme essential 1805:1813 arg1 DNA 1771:1773 DNA 1771:1773 DNA in extracellular matrix 1771:1797 Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture. 36854956 8 1 theme essential 1805:1813 arg1 factor 1815:1820 an essential factor 1802:1820 an essential factor for triggering the biomineralization in B. cereus planktonic culture 1802:1889 Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture. 36854956 5 2 theme DNA 1126:1128 arg1 addition 1091:1098 the addition 1087:1098 the addition of exogenous salmon sperm DNA 1087:1128 An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. 36854956 6 3 dep B. 1191:1192 arg1 cereus 1194:1199 cereus 1194:1199 cereus 1194:1199 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 6 4 theme insoluble 1458:1466 arg1 precipitate 1468:1478 an insoluble precipitate 1455:1478 an insoluble precipitate of calcium carbonate 1455:1499 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 2 5 from influence 306:314 arg1 induction 348:356 the induction 344:356 the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture 344:490 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 3 6 theme DNA 678:680 arg1 accumulation 648:659 the accumulation 644:659 the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, 644:735 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 6 7 theme CaCO3 1173:1177 arg1 minerals 1179:1186 CaCO3 minerals 1173:1186 CaCO3 minerals 1173:1186 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 1 8 theme biomineralization 153:169 arg1 mechanisms 139:148 the mechanisms 135:148 the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation 135:232 To date, the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation remain the subject of intensive studies. 36854956 7 9 theme crystal 1566:1572 arg1 formation 1574:1582 crystal formation 1566:1582 crystal formation via the ACC-vaterite-calcite/aragonite pathway 1566:1629 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 0 10 theme planktonic 104:113 arg1 lifestyle 115:123 Bacillus cereus planktonic lifestyle 88:123 Bacillus cereus planktonic lifestyle 88:123 Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle. 36854956 6 11 from increase 1362:1369 arg1 concentration 1378:1390 the concentration 1374:1390 the concentration of carbonate ions due to pH rise 1374:1423 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 3 12 theme extracellular 519:531 arg1 polysaccharides 533:547 extracellular polysaccharides 519:547 extracellular polysaccharides 519:547 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 0 13 from biofilm 58:64 arg1 lifestyle 115:123 Bacillus cereus planktonic lifestyle 88:123 Bacillus cereus planktonic lifestyle 88:123 Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle. 36854956 7 14 from formation 1574:1582 arg1 complex 1685:1691 complex 1685:1691 complex with extracellular polymeric substances 1685:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 3 15 theme calcium 718:724 arg1 carbonate 726:734 calcium carbonate 718:734 calcium carbonate 718:734 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 6 16 from formation 1160:1168 arg1 culture 1212:1218 B. cereus planktonic culture 1191:1218 B. cereus planktonic culture 1191:1218 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 3 17 theme precipitation 701:713 arg1 accumulation 648:659 the accumulation 644:659 the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, 644:735 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 3 18 theme presence 596:603 arg1 accumulation 503:514 the accumulation 499:514 the accumulation of extracellular polysaccharides and amyloids 499:560 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 3 18 theme presence 596:603 arg1 independent 577:587 independent 577:587 independent 577:587 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 6 19 theme carbonate 1491:1499 arg1 precipitate 1468:1478 an insoluble precipitate 1455:1478 an insoluble precipitate of calcium carbonate 1455:1499 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 7 20 theme amorphous 1519:1527 arg1 CaCO3 1529:1533 amorphous CaCO3 1519:1533 amorphous CaCO3 1519:1533 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 8 21 dep B. 1862:1863 arg1 cereus 1865:1870 cereus 1865:1870 cereus 1865:1870 Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture. 36854956 0 22 from mineralization 70:83 arg1 lifestyle 115:123 Bacillus cereus planktonic lifestyle 88:123 Bacillus cereus planktonic lifestyle 88:123 Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle. 36854956 7 23 theme mineral 1663:1669 arg1 aggregates 1671:1680 larger mineral aggregates 1656:1680 larger mineral aggregates in complex with extracellular polymeric substances 1656:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 3 24 theme ingredients 767:777 arg1 presence 750:757 the presence 746:757 the presence of both ingredients in the medium 746:791 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 6 25 theme local 1310:1314 arg1 supersaturation 1321:1335 local Ca2+ supersaturation 1310:1335 local Ca2+ supersaturation 1310:1335 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 4 26 from decrease 960:967 arg1 yield 988:992 the precipitate yield 972:992 the precipitate yield 972:992 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 6 27 theme lattice 1292:1298 arg1 production 1231:1240 a production 1229:1240 a production 1229:1240 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 0 28 dep Bacillus 88:95 arg1 cereus 97:102 cereus 97:102 cereus 97:102 Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle. 36854956 7 29 theme further 1635:1641 arg1 formation 1643:1651 further formation 1635:1651 further formation of larger mineral aggregates in complex with extracellular polymeric substances 1635:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 4 30 theme matrix 875:880 arg1 components 882:891 other matrix components 869:891 other matrix components 869:891 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 7 31 with complex 1685:1691 arg1 substances 1722:1731 extracellular polymeric substances 1698:1731 extracellular polymeric substances 1698:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 2 32 theme CaCO3 361:365 arg1 precipitation 367:379 CaCO3 precipitation 361:379 CaCO3 precipitation 361:379 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 0 33 theme Bacillus 88:95 arg1 lifestyle 115:123 Bacillus cereus planktonic lifestyle 88:123 Bacillus cereus planktonic lifestyle 88:123 Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle. 36854956 5 34 theme cell-free 1016:1024 arg1 system 1026:1031 a cell-free system 1014:1031 a cell-free system 1014:1031 An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. 36854956 1 35 theme intensive 256:264 arg1 studies 266:272 intensive studies 256:272 intensive studies 256:272 To date, the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation remain the subject of intensive studies. 36854956 4 36 theme sixfold 952:958 arg1 decrease 960:967 a sixfold decrease 950:967 a sixfold decrease in the precipitate yield 950:992 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 5 37 with experiment 998:1007 arg1 system 1026:1031 a cell-free system 1014:1031 a cell-free system 1014:1031 An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. 36854956 2 38 theme Bacillus 388:395 arg1 cells 404:408 Bacillus cereus cells 388:408 Bacillus cereus cells 388:408 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 5 39 theme exogenous 1103:1111 arg1 DNA 1126:1128 exogenous salmon sperm DNA 1103:1128 exogenous salmon sperm DNA 1103:1128 An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. 36854956 2 40 theme matrix 447:452 arg1 composition 414:424 composition 414:424 composition 414:424 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 2 40 theme matrix 447:452 arg1 cells 404:408 Bacillus cereus cells 388:408 Bacillus cereus cells 388:408 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 3 41 theme urea 620:623 arg1 presence 596:603 the presence 592:603 the presence of calcium and urea 592:623 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 0 42 theme extracellular 22:34 arg1 DNA 36:38 extracellular DNA 22:38 extracellular DNA 22:38 Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle. 36854956 0 42 theme extracellular 22:34 arg1 link 45:48 a link 43:48 a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle 43:123 Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle. 36854956 5 43 theme mineral 1063:1069 arg1 formation 1071:1079 mineral formation 1063:1079 mineral formation 1063:1079 An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. 36854956 4 44 theme network 928:934 arg1 formation 936:944 cell network formation 923:944 cell network formation 923:944 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 3 45 theme calcium 608:614 arg1 presence 596:603 the presence 592:603 the presence of calcium and urea 592:623 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 2 46 dep Bacillus 388:395 arg1 cereus 397:402 cereus 397:402 cereus 397:402 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 7 47 from Precipitation 1502:1514 arg1 matrix 1543:1548 eDNA matrix 1538:1548 eDNA matrix 1538:1548 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 6 48 theme pH 1417:1418 arg1 rise 1420:1423 pH rise 1417:1423 pH rise 1417:1423 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 2 49 theme precipitation 367:379 arg1 induction 348:356 the induction 344:356 the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture 344:490 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 1 50 theme biofilm 216:222 arg1 formation 224:232 biofilm formation 216:232 biofilm formation 216:232 To date, the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation remain the subject of intensive studies. 36854956 3 51 theme extracellular 664:676 arg1 eDNA 683:686 eDNA 683:686 eDNA 683:686 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 3 51 theme extracellular 664:676 arg1 DNA 678:680 extracellular DNA 664:680 extracellular DNA (eDNA) 664:687 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 6 52 theme planktonic 1201:1210 arg1 culture 1212:1218 B. cereus planktonic culture 1191:1218 B. cereus planktonic culture 1191:1218 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 2 53 theme medium 323:328 arg1 components 330:339 the medium components 319:339 the medium components 319:339 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 6 54 theme carbonate 1395:1403 arg1 ions 1405:1408 carbonate ions 1395:1408 carbonate ions 1395:1408 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 5 55 theme sperm 1120:1124 arg1 DNA 1126:1128 exogenous salmon sperm DNA 1103:1128 exogenous salmon sperm DNA 1103:1128 An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. 36854956 4 56 theme precipitate 976:986 arg1 yield 988:992 the precipitate yield 972:992 the precipitate yield 972:992 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 6 57 theme B. 1191:1192 arg1 culture 1212:1218 B. cereus planktonic culture 1191:1218 B. cereus planktonic culture 1191:1218 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 6 58 theme minerals 1179:1186 arg1 formation 1160:1168 the formation 1156:1168 the formation of CaCO3 minerals in B. cereus planktonic culture 1156:1218 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 7 59 from aggregates 1671:1680 arg1 complex 1685:1691 complex 1685:1691 complex with extracellular polymeric substances 1685:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 8 60 theme B. 1862:1863 arg1 culture 1883:1889 B. cereus planktonic culture 1862:1889 B. cereus planktonic culture 1862:1889 Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture. 36854956 3 61 theme polysaccharides 533:547 arg1 accumulation 503:514 the accumulation 499:514 the accumulation of extracellular polysaccharides and amyloids 499:560 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 3 61 theme polysaccharides 533:547 arg1 independent 577:587 independent 577:587 independent 577:587 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 7 62 theme polymeric 1712:1720 arg1 substances 1722:1731 extracellular polymeric substances 1698:1731 extracellular polymeric substances 1698:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 7 63 from complex 1685:1691 arg1 formation 1574:1582 crystal formation 1566:1582 crystal formation via the ACC-vaterite-calcite/aragonite pathway 1566:1629 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 7 63 from complex 1685:1691 arg1 formation 1643:1651 further formation 1635:1651 further formation of larger mineral aggregates in complex with extracellular polymeric substances 1635:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 8 64 theme planktonic 1872:1881 arg1 culture 1883:1889 B. cereus planktonic culture 1862:1889 B. cereus planktonic culture 1862:1889 Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture. 36854956 1 65 theme bacterial 182:190 arg1 cells 192:196 bacterial cells 182:196 bacterial cells 182:196 To date, the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation remain the subject of intensive studies. 36854956 6 66 theme exopolysaccharides 1245:1262 arg1 production 1231:1240 a production 1229:1240 a production 1229:1240 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 7 67 theme eDNA 1538:1541 arg1 matrix 1543:1548 eDNA matrix 1538:1548 eDNA matrix 1538:1548 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 3 68 theme carbonate 726:734 arg1 eDNA 683:686 eDNA 683:686 eDNA 683:686 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 3 68 theme carbonate 726:734 arg1 precipitation 701:713 precipitation 701:713 precipitation of calcium carbonate 701:734 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 3 68 theme carbonate 726:734 arg1 DNA 678:680 extracellular DNA 664:680 extracellular DNA (eDNA) 664:687 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 3 69 theme amyloids 553:560 arg1 accumulation 503:514 the accumulation 499:514 the accumulation of extracellular polysaccharides and amyloids 499:560 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 3 69 theme amyloids 553:560 arg1 independent 577:587 independent 577:587 independent 577:587 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 7 70 theme CaCO3 1529:1533 arg1 Precipitation 1502:1514 Precipitation 1502:1514 Precipitation of amorphous CaCO3 on eDNA matrix 1502:1548 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 6 71 theme observed 1135:1142 arg1 pathway 1144:1150 The observed pathway 1131:1150 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture 1131:1218 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 8 72 from DNA 1771:1773 arg1 matrix 1792:1797 extracellular matrix 1778:1797 extracellular matrix 1778:1797 Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture. 36854956 7 73 theme extracellular 1698:1710 arg1 substances 1722:1731 extracellular polymeric substances 1698:1731 extracellular polymeric substances 1698:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 6 74 theme calcium 1483:1489 arg1 carbonate 1491:1499 calcium carbonate 1483:1499 calcium carbonate 1483:1499 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 7 75 from formation 1643:1651 arg1 complex 1685:1691 complex 1685:1691 complex with extracellular polymeric substances 1685:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 6 76 theme Ca2+ 1316:1319 arg1 supersaturation 1321:1335 local Ca2+ supersaturation 1310:1335 local Ca2+ supersaturation 1310:1335 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 6 77 theme precipitate 1468:1478 arg1 formation 1442:1450 the formation 1438:1450 the formation of an insoluble precipitate of calcium carbonate 1438:1499 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 7 78 theme aggregates 1671:1680 arg1 formation 1574:1582 crystal formation 1566:1582 crystal formation via the ACC-vaterite-calcite/aragonite pathway 1566:1629 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 7 78 theme aggregates 1671:1680 arg1 formation 1643:1651 further formation 1635:1651 further formation of larger mineral aggregates in complex with extracellular polymeric substances 1635:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 7 79 theme larger 1656:1661 arg1 aggregates 1671:1680 larger mineral aggregates 1656:1680 larger mineral aggregates in complex with extracellular polymeric substances 1656:1731 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 2 80 theme submerged 474:482 arg1 culture 484:490 the submerged culture 470:490 the submerged culture 470:490 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 6 81 theme eDNA 1287:1290 arg1 lattice 1292:1298 negatively charged eDNA lattice 1268:1298 negatively charged eDNA lattice 1268:1298 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 2 82 dep cells 404:408 arg1 the 384:386 the 384:386 the 384:386 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 4 83 theme other 869:873 arg1 components 882:891 other matrix components 869:891 other matrix components 869:891 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 8 84 theme extracellular 1778:1790 arg1 matrix 1792:1797 extracellular matrix 1778:1797 extracellular matrix 1778:1797 Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture. 36854956 4 85 theme formation 936:944 arg1 disruption 909:918 disruption 909:918 disruption of cell network formation 909:944 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 4 85 theme formation 936:944 arg1 decrease 960:967 a sixfold decrease 950:967 a sixfold decrease in the precipitate yield 950:992 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 3 86 attach presence 750:757 arg2 ingredients 767:777 both ingredients 762:777 both ingredients 762:777 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 3 86 attach presence 750:757 arg1 medium 786:791 the medium 782:791 the medium 782:791 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 1 87 theme studies 266:272 arg1 subject 245:251 the subject 241:251 the subject of intensive studies 241:272 To date, the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation remain the subject of intensive studies. 36854956 7 88 theme ACC-vaterite-calcite/aragonite 1592:1621 arg1 pathway 1623:1629 the ACC-vaterite-calcite/aragonite pathway 1588:1629 the ACC-vaterite-calcite/aragonite pathway 1588:1629 Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. 36854956 5 89 theme salmon 1113:1118 arg1 DNA 1126:1128 exogenous salmon sperm DNA 1103:1128 exogenous salmon sperm DNA 1103:1128 An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. 36854956 2 90 theme extracellular 433:445 arg1 ECM 455:457 ECM 455:457 ECM 455:457 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 2 90 theme extracellular 433:445 arg1 matrix 447:452 the extracellular matrix 429:452 the extracellular matrix (ECM) formed in the submerged culture 429:490 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 6 91 theme charged 1279:1285 arg1 lattice 1292:1298 negatively charged eDNA lattice 1268:1298 negatively charged eDNA lattice 1268:1298 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 5 92 theme formation 1071:1079 arg1 acceleration 1047:1058 the acceleration 1043:1058 the acceleration of mineral formation 1043:1079 An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. 36854956 4 93 theme cell 923:926 arg1 formation 936:944 cell network formation 923:944 cell network formation 923:944 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 8 94 from biomineralization 1841:1857 arg1 culture 1883:1889 B. cereus planktonic culture 1862:1889 B. cereus planktonic culture 1862:1889 Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture. 36854956 4 95 from disruption 909:918 arg1 yield 988:992 the precipitate yield 972:992 the precipitate yield 972:992 Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. 36854956 3 96 from presence 750:757 arg1 medium 786:791 the medium 782:791 the medium 782:791 While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. 36854956 2 97 theme components 330:339 arg1 influence 306:314 the influence 302:314 the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture 302:490 In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. 36854956 6 98 theme ions 1405:1408 arg1 concentration 1378:1390 the concentration 1374:1390 the concentration of carbonate ions due to pH rise 1374:1423 The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. 36854956 1 99 theme formation 224:232 arg1 context 205:211 the context 201:211 the context of biofilm formation 201:232 To date, the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation remain the subject of intensive studies. 36432874 7 0 theme pectin 1171:1176 arg1 distribution 1178:1189 pectin distribution 1171:1189 pectin distribution 1171:1189 Herein, we demonstrate that these factors regulate specific aspects of cell wall properties such as pectin distribution. 36432874 0 1 from Control 12:18 arg1 Development 70:80 Seed and Fruit Development 55:80 Seed and Fruit Development 55:80 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 36432874 1 2 from impact 273:278 arg1 plants 307:312 plants 307:312 plants 307:312 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 8 3 from changes 1219:1225 arg1 structure 1240:1248 seed coat structure 1230:1248 seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation 1230:1335 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 6 4 theme seed 1058:1061 arg1 growth 1063:1068 seed growth 1058:1068 seed growth 1058:1068 Finally, we focused on two transcriptional regulators, SEEDSTICK (STK) and LEUNIG-HOMOLOG (LUH), which positively regulate seed growth. 36432874 0 5 theme Fruit 64:68 arg1 Development 70:80 Seed and Fruit Development 55:80 Seed and Fruit Development 55:80 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 36432874 3 6 theme developmental 651:663 arg1 defects 665:671 seed and fruit size developmental defects 631:671 seed and fruit size developmental defects 631:671 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 9 7 theme wall 1431:1434 arg1 properties 1436:1445 cell wall properties 1426:1445 cell wall properties 1426:1445 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 8 8 from alterations 1257:1267 arg1 deposition 1304:1313 the xyloglucan-cellulose matrix deposition 1272:1313 the xyloglucan-cellulose matrix deposition 1272:1313 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 8 8 from alterations 1257:1267 arg1 maturation 1326:1335 pectin maturation 1319:1335 pectin maturation 1319:1335 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 3 9 theme wall-related 608:619 arg1 genes 621:625 representative cell wall-related genes 588:625 representative cell wall-related genes for seed and fruit size developmental defects 588:671 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 9 10 theme polysaccharides 1465:1479 arg1 importance 1412:1421 the importance 1408:1421 the importance of cell wall properties 1408:1445 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 9 10 theme polysaccharides 1465:1479 arg1 factors 1490:1496 major factors 1484:1496 major factors responsible for seed development 1484:1529 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 9 10 theme polysaccharides 1465:1479 arg1 remodeling 1451:1460 remodeling 1451:1460 remodeling of polysaccharides 1451:1479 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 0 11 theme New 83:85 arg1 Insights 87:94 New Insights 83:94 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 0:118 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 36432874 3 12 theme representative 588:601 arg1 genes 621:625 representative cell wall-related genes 588:625 representative cell wall-related genes for seed and fruit size developmental defects 588:671 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 6 13 theme transcriptional 962:976 arg1 regulators 978:987 two transcriptional regulators 958:987 two transcriptional regulators 958:987 Finally, we focused on two transcriptional regulators, SEEDSTICK (STK) and LEUNIG-HOMOLOG (LUH), which positively regulate seed growth. 36432874 6 13 theme transcriptional 962:976 arg1 LEUNIG-HOMOLOG 1010:1023 LEUNIG-HOMOLOG 1010:1023 LEUNIG-HOMOLOG (LUH) 1010:1029 Finally, we focused on two transcriptional regulators, SEEDSTICK (STK) and LEUNIG-HOMOLOG (LUH), which positively regulate seed growth. 36432874 6 13 theme transcriptional 962:976 arg1 SEEDSTICK 990:998 SEEDSTICK 990:998 SEEDSTICK (STK) 990:1004 Finally, we focused on two transcriptional regulators, SEEDSTICK (STK) and LEUNIG-HOMOLOG (LUH), which positively regulate seed growth. 36432874 2 14 theme families 480:487 arg1 function 463:470 the function 459:470 the function of gene families devoted to cell wall biogenesis 459:519 Mutants of Arabidopsis thaliana constitute an excellent tool to study the function of gene families devoted to cell wall biogenesis. 36432874 3 15 theme altered 685:691 arg1 rates 705:709 altered germination rates 685:709 altered germination rates 685:709 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 8 16 theme matrix 1297:1302 arg1 deposition 1304:1313 the xyloglucan-cellulose matrix deposition 1272:1313 the xyloglucan-cellulose matrix deposition 1272:1313 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 2 17 theme gene 475:478 arg1 families 480:487 gene families 475:487 gene families devoted to cell wall biogenesis 475:519 Mutants of Arabidopsis thaliana constitute an excellent tool to study the function of gene families devoted to cell wall biogenesis. 36432874 3 18 theme germination 693:703 arg1 rates 705:709 altered germination rates 685:709 altered germination rates 685:709 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 2 19 theme wall 505:508 arg1 biogenesis 510:519 cell wall biogenesis 500:519 cell wall biogenesis 500:519 Mutants of Arabidopsis thaliana constitute an excellent tool to study the function of gene families devoted to cell wall biogenesis. 36432874 8 20 dep wherein 1211:1217 arg1 critical 1341:1348 critical 1341:1348 critical 1341:1348 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 3 21 from mutations 575:583 arg1 genes 621:625 representative cell wall-related genes 588:625 representative cell wall-related genes for seed and fruit size developmental defects 588:671 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 7 22 theme properties 1152:1161 arg1 aspects 1131:1137 specific aspects 1122:1137 specific aspects of cell wall properties such as pectin distribution 1122:1189 Herein, we demonstrate that these factors regulate specific aspects of cell wall properties such as pectin distribution. 36432874 7 22 theme properties 1152:1161 arg1 distribution 1178:1189 pectin distribution 1171:1189 pectin distribution 1171:1189 Herein, we demonstrate that these factors regulate specific aspects of cell wall properties such as pectin distribution. 36432874 7 23 theme cell 1142:1145 arg1 properties 1152:1161 cell wall properties 1142:1161 cell wall properties 1142:1161 Herein, we demonstrate that these factors regulate specific aspects of cell wall properties such as pectin distribution. 36432874 1 24 theme seed 149:152 arg1 development 164:174 seed and fruit development 149:174 seed and fruit development at the molecular level 149:197 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 0 25 theme Genetic 4:10 arg1 Control 12:18 The Genetic Control 0:18 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 0:118 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 36432874 9 26 theme seed 1514:1517 arg1 development 1519:1529 seed development 1514:1529 seed development 1514:1529 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 5 27 theme germination 913:923 arg1 dynamics 925:932 germination dynamics 913:932 germination dynamics 913:932 Interestingly, we have found that disruption of genes involved in pectin maturation and hemicellulose deposition strongly influence germination dynamics. 36432874 4 28 dep wall 749:752 arg1 composition 754:764 composition 754:764 composition 754:764 We have linked these studies to cell wall composition and structure. 36432874 4 28 dep wall 749:752 arg1 structure 770:778 structure 770:778 structure 770:778 We have linked these studies to cell wall composition and structure. 36432874 2 29 theme Arabidopsis 400:410 arg1 thaliana 412:419 Arabidopsis thaliana 400:419 Arabidopsis thaliana 400:419 Mutants of Arabidopsis thaliana constitute an excellent tool to study the function of gene families devoted to cell wall biogenesis. 36432874 4 30 attach linked 720:725 arg1 wall 749:752 cell wall composition and structure 744:778 cell wall composition and structure 744:778 We have linked these studies to cell wall composition and structure. 36432874 4 30 attach linked 720:725 arg2 We 712:713 We 712:713 We 712:713 We have linked these studies to cell wall composition and structure. 36432874 3 31 from rates 705:709 arg1 genes 621:625 representative cell wall-related genes 588:625 representative cell wall-related genes for seed and fruit size developmental defects 588:671 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 1 32 theme fruit 158:162 arg1 development 164:174 seed and fruit development 149:174 seed and fruit development at the molecular level 149:197 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 7 33 theme specific 1122:1129 arg1 aspects 1131:1137 specific aspects 1122:1137 specific aspects of cell wall properties such as pectin distribution 1122:1189 Herein, we demonstrate that these factors regulate specific aspects of cell wall properties such as pectin distribution. 36432874 7 33 theme specific 1122:1129 arg1 distribution 1178:1189 pectin distribution 1171:1189 pectin distribution 1171:1189 Herein, we demonstrate that these factors regulate specific aspects of cell wall properties such as pectin distribution. 36432874 0 34 theme Wall 106:109 arg1 Control 111:117 Cell Wall Control 101:117 Cell Wall Control 101:117 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 36432874 8 35 theme organ 1354:1358 arg1 growth 1360:1365 organ growth 1354:1365 organ growth 1354:1365 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 9 36 theme cell 1426:1429 arg1 properties 1436:1445 cell wall properties 1426:1445 cell wall properties 1426:1445 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 9 37 theme properties 1436:1445 arg1 importance 1412:1421 the importance 1408:1421 the importance of cell wall properties 1408:1445 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 9 37 theme properties 1436:1445 arg1 factors 1490:1496 major factors 1484:1496 major factors responsible for seed development 1484:1529 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 9 37 theme properties 1436:1445 arg1 remodeling 1451:1460 remodeling 1451:1460 remodeling of polysaccharides 1451:1479 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 1 38 theme cell 245:248 arg1 modifications 255:267 cell wall modifications 245:267 cell wall modifications 245:267 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 0 39 theme Cell 101:104 arg1 Control 111:117 Cell Wall Control 101:117 Cell Wall Control 101:117 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 36432874 1 40 theme biomechanical 330:342 arg1 alterations 344:354 biomechanical alterations 330:354 biomechanical alterations 330:354 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 4 41 theme cell 744:747 arg1 wall 749:752 cell wall composition and structure 744:778 cell wall composition and structure 744:778 We have linked these studies to cell wall composition and structure. 36432874 1 42 theme wall 250:253 arg1 modifications 255:267 cell wall modifications 245:267 cell wall modifications 245:267 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 2 43 theme cell 500:503 arg1 biogenesis 510:519 cell wall biogenesis 500:519 cell wall biogenesis 500:519 Mutants of Arabidopsis thaliana constitute an excellent tool to study the function of gene families devoted to cell wall biogenesis. 36432874 8 44 theme model 1205:1209 arg1 wherein 1211:1217 a model wherein 1203:1217 a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination 1203:1381 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 8 45 theme coat 1235:1238 arg1 structure 1240:1248 seed coat structure 1230:1248 seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation 1230:1335 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 0 46 theme SEEDSTICK 23:31 arg1 Control 12:18 The Genetic Control 0:18 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 0:118 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 36432874 2 47 theme excellent 435:443 arg1 tool 445:448 an excellent tool 432:448 an excellent tool to study the function of gene families devoted to cell wall biogenesis 432:519 Mutants of Arabidopsis thaliana constitute an excellent tool to study the function of gene families devoted to cell wall biogenesis. 36432874 3 48 theme cell 603:606 arg1 genes 621:625 representative cell wall-related genes 588:625 representative cell wall-related genes for seed and fruit size developmental defects 588:671 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 3 49 theme lines 560:564 arg1 collection 546:555 a collection 544:555 a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates 544:709 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 8 50 theme xyloglucan-cellulose 1276:1295 arg1 deposition 1304:1313 the xyloglucan-cellulose matrix deposition 1272:1313 the xyloglucan-cellulose matrix deposition 1272:1313 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 1 51 theme molecular 183:191 arg1 level 193:197 the molecular level 179:197 the molecular level 179:197 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 8 52 theme due 1250:1252 arg1 structure 1240:1248 seed coat structure 1230:1248 seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation 1230:1335 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 5 53 theme genes 829:833 arg1 disruption 815:824 disruption 815:824 disruption of genes involved in pectin maturation and hemicellulose deposition 815:892 Interestingly, we have found that disruption of genes involved in pectin maturation and hemicellulose deposition strongly influence germination dynamics. 36432874 1 54 theme seed 366:369 arg1 growth 381:386 seed and fruit growth 366:386 seed and fruit growth 366:386 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 5 55 theme hemicellulose 869:881 arg1 deposition 883:892 hemicellulose deposition 869:892 hemicellulose deposition 869:892 Interestingly, we have found that disruption of genes involved in pectin maturation and hemicellulose deposition strongly influence germination dynamics. 36432874 0 56 theme LEUNIG-HOMOLOG 37:50 arg1 Control 12:18 The Genetic Control 0:18 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 0:118 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 36432874 3 57 theme fruit 640:644 arg1 defects 665:671 seed and fruit size developmental defects 631:671 seed and fruit size developmental defects 631:671 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 3 58 theme size 646:649 arg1 defects 665:671 seed and fruit size developmental defects 631:671 seed and fruit size developmental defects 631:671 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 1 59 theme developmental 280:292 arg1 processes 294:302 developmental processes 280:302 developmental processes 280:302 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 1 60 from level 193:197 arg1 development 164:174 seed and fruit development 149:174 seed and fruit development at the molecular level 149:197 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 1 61 theme fruit 375:379 arg1 growth 381:386 seed and fruit growth 366:386 seed and fruit growth 366:386 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 9 62 theme major 1484:1488 arg1 importance 1412:1421 the importance 1408:1421 the importance of cell wall properties 1408:1445 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 9 62 theme major 1484:1488 arg1 factors 1490:1496 major factors 1484:1496 major factors responsible for seed development 1484:1529 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 9 62 theme major 1484:1488 arg1 remodeling 1451:1460 remodeling 1451:1460 remodeling of polysaccharides 1451:1479 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 8 63 theme pectin 1319:1324 arg1 maturation 1326:1335 pectin maturation 1319:1335 pectin maturation 1319:1335 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 3 64 theme seed 631:634 arg1 defects 665:671 seed and fruit size developmental defects 631:671 seed and fruit size developmental defects 631:671 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 0 65 dep Control 12:18 arg1 Insights 87:94 New Insights 83:94 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 0:118 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 36432874 5 66 theme pectin 847:852 arg1 maturation 854:863 pectin maturation 847:863 pectin maturation 847:863 Interestingly, we have found that disruption of genes involved in pectin maturation and hemicellulose deposition strongly influence germination dynamics. 36432874 3 67 contain carrying 566:573 arg2 rates 705:709 altered germination rates 685:709 altered germination rates 685:709 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 3 67 contain carrying 566:573 arg2 mutations 575:583 mutations 575:583 mutations in representative cell wall-related genes for seed and fruit size developmental defects 575:671 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 3 67 contain carrying 566:573 arg1 lines 560:564 lines 560:564 lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates 560:709 We have characterized a collection of lines carrying mutations in representative cell wall-related genes for seed and fruit size developmental defects, as well as altered germination rates. 36432874 8 68 theme seed 1230:1233 arg1 structure 1240:1248 seed coat structure 1230:1248 seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation 1230:1335 We propose a model wherein changes in seed coat structure due to alterations in the xyloglucan-cellulose matrix deposition and pectin maturation are critical for organ growth and germination. 36432874 9 69 theme responsible 1498:1508 arg1 importance 1412:1421 the importance 1408:1421 the importance of cell wall properties 1408:1445 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 9 69 theme responsible 1498:1508 arg1 factors 1490:1496 major factors 1484:1496 major factors responsible for seed development 1484:1529 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 9 69 theme responsible 1498:1508 arg1 remodeling 1451:1460 remodeling 1451:1460 remodeling of polysaccharides 1451:1479 The results demonstrate the importance of cell wall properties and remodeling of polysaccharides as major factors responsible for seed development. 36432874 1 70 theme many 200:203 arg1 gaps 205:208 many gaps 200:208 many gaps 200:208 Although much is known about seed and fruit development at the molecular level, many gaps remain in our understanding of how cell wall modifications can impact developmental processes in plants, as well as how biomechanical alterations influence seed and fruit growth. 36432874 0 71 theme Seed 55:58 arg1 Development 70:80 Seed and Fruit Development 55:80 Seed and Fruit Development 55:80 The Genetic Control of SEEDSTICK and LEUNIG-HOMOLOG in Seed and Fruit Development: New Insights into Cell Wall Control. 36432874 7 72 theme wall 1147:1150 arg1 properties 1152:1161 cell wall properties 1142:1161 cell wall properties 1142:1161 Herein, we demonstrate that these factors regulate specific aspects of cell wall properties such as pectin distribution. 36432874 2 73 theme thaliana 412:419 arg1 Mutants 389:395 Mutants 389:395 Mutants of Arabidopsis thaliana 389:419 Mutants of Arabidopsis thaliana constitute an excellent tool to study the function of gene families devoted to cell wall biogenesis. 35088787 10 0 theme signaling 2064:2072 arg1 pathway 2074:2080 the AMP-activated protein kinase signaling pathway 2031:2080 the AMP-activated protein kinase signaling pathway 2031:2080 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 8 1 theme microorganisms 1448:1461 arg1 number 1420:1425 the number 1416:1425 the number of unique intestinal microorganisms in GK rats 1416:1472 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35088787 7 2 theme hepatic 1267:1273 arg1 HL 1283:1284 HL 1283:1284 HL 1283:1284 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 2 theme hepatic 1267:1273 arg1 lipase 1275:1280 hepatic lipase 1267:1280 hepatic lipase (HL) 1267:1285 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 10 3 theme protein 2049:2055 arg1 pathway 2074:2080 the AMP-activated protein kinase signaling pathway 2031:2080 the AMP-activated protein kinase signaling pathway 2031:2080 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 6 4 theme GK 1037:1038 arg1 group 1048:1052 the GK control group 1033:1052 the GK control group (P < 0.05) 1033:1063 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 6 4 theme GK 1037:1038 arg1 < 1057:1057 P < 0.05 1055:1062 P < 0.05 1055:1062 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 12 5 theme serum 2299:2303 arg1 TG 2311:2312 serum lipid TG 2299:2312 serum lipid TG 2299:2312 Furthermore, BT significantly reduced serum lipid TG and total cholesterol (TC) and BA significantly reduced the serum lipid TC and low-density lipoprotein (LDL). 35088787 8 6 theme treatment 1400:1408 arg1 time 1410:1413 treatment time 1400:1413 treatment time 1400:1413 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35088787 8 7 theme GK 1466:1467 arg1 rats 1469:1472 GK rats 1466:1472 GK rats 1466:1472 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35088787 10 8 theme signaling 2091:2099 arg1 pathway 2101:2107 insulin signaling pathway 2083:2107 insulin signaling pathway 2083:2107 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 7 9 theme GK 1220:1221 arg1 group 1223:1227 the GK group 1216:1227 the GK group 1216:1227 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 10 theme glucokinase 1125:1135 arg1 levels 1137:1142 glucokinase levels 1125:1142 glucokinase levels 1125:1142 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 10 theme glucokinase 1125:1135 arg1 Meanwhile 1066:1074 Meanwhile 1066:1074 Meanwhile 1066:1074 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 15 11 with component 2758:2766 arg1 potential 2779:2787 great potential 2773:2787 great potential 2773:2787 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 14 12 from content 2551:2557 arg1 serum 2570:2574 serum 2570:2574 serum 2570:2574 However, LM and PD significantly increased the content of ADPN in serum. 35088787 2 13 theme abundant 255:262 arg1 pigments 264:271 the most active and abundant pigments 235:271 the most active and abundant pigments in Pu-erh tea 235:285 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 14 14 theme ADPN 2562:2565 arg1 content 2551:2557 the content 2547:2557 the content of ADPN in serum 2547:2574 However, LM and PD significantly increased the content of ADPN in serum. 35088787 12 15 theme lipid 2380:2384 arg1 TC 2386:2387 the serum lipid TC 2370:2387 the serum lipid TC 2370:2387 Furthermore, BT significantly reduced serum lipid TG and total cholesterol (TC) and BA significantly reduced the serum lipid TC and low-density lipoprotein (LDL). 35088787 4 16 theme intestinal 698:707 arg1 microbes 709:716 intestinal microbes 698:716 intestinal microbes 698:716 This study aimed to determine the effect of TB in treating diabetes and explore the underlying mechanism of action of intestinal microbes by using Goto-Kakizaki (GK) rats. 35088787 1 17 theme metabolism 196:205 arg1 disturbance 173:183 a disturbance 171:183 a disturbance of glucose metabolism 171:205 Diabetes is a disease that is characterized by a disturbance of glucose metabolism. 35088787 3 18 theme high-fat 511:518 arg1 diet 520:523 a high-fat diet 509:523 a high-fat diet 509:523 TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. 35088787 11 19 from HOMA-IR 2241:2247 arg1 rats 2255:2258 GK rats 2252:2258 GK rats 2252:2258 Intragastric administration of BT, LM, PD, or BA led to a significantly reduced HOMA-IR in GK rats. 35088787 0 20 from metabolism 90:99 arg1 rats 118:121 Goto-Kakizaki rats 104:121 Goto-Kakizaki rats 104:121 Theabrownin-targeted regulation of intestinal microorganisms to improve glucose and lipid metabolism in Goto-Kakizaki rats. 35088787 15 21 theme microorganisms 2710:2723 arg1 regulation 2685:2694 the targeted regulation 2672:2694 the targeted regulation of intestinal microorganisms 2672:2723 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 8 22 theme intestinal 1517:1526 arg1 microorganisms 1528:1541 intestinal microorganisms 1517:1541 intestinal microorganisms 1517:1541 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35088787 6 23 theme body 838:841 arg1 weight 843:848 the body weight 834:848 the body weight 834:848 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 6 23 theme body 838:841 arg1 lower 1000:1004 lower 1000:1004 lower 1000:1004 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 7 24 theme group 1170:1174 arg1 serum 1151:1155 the serum 1147:1155 the serum of the GK-TB group 1147:1174 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 12 25 theme low-density 2393:2403 arg1 lipoprotein 2405:2415 low-density lipoprotein 2393:2415 low-density lipoprotein (LDL) 2393:2421 Furthermore, BT significantly reduced serum lipid TG and total cholesterol (TC) and BA significantly reduced the serum lipid TC and low-density lipoprotein (LDL). 35088787 12 25 theme low-density 2393:2403 arg1 LDL 2418:2420 LDL 2418:2420 LDL 2418:2420 Furthermore, BT significantly reduced serum lipid TG and total cholesterol (TC) and BA significantly reduced the serum lipid TC and low-density lipoprotein (LDL). 35088787 2 26 from pigments 264:271 arg1 tea 283:285 Pu-erh tea 276:285 Pu-erh tea 276:285 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 11 27 theme LM 2196:2197 arg1 administration 2174:2187 Intragastric administration 2161:2187 Intragastric administration of BT, LM, PD, or BA 2161:2208 Intragastric administration of BT, LM, PD, or BA led to a significantly reduced HOMA-IR in GK rats. 35088787 10 28 theme glycerophospholipid 2129:2147 arg1 metabolism 2149:2158 glycerophospholipid metabolism 2129:2158 glycerophospholipid metabolism 2129:2158 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 6 29 theme P 1055:1055 arg1 group 1048:1052 the GK control group 1033:1052 the GK control group (P < 0.05) 1033:1063 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 6 29 theme P 1055:1055 arg1 < 1057:1057 P < 0.05 1055:1062 P < 0.05 1055:1062 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 10 30 theme flora 1822:1826 arg1 regulation 1773:1782 the targeted regulation 1760:1782 the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism 1760:2158 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 2 31 theme active 244:249 arg1 pigments 264:271 the most active and abundant pigments 235:271 the most active and abundant pigments in Pu-erh tea 235:285 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 11 32 theme reduced 2233:2239 arg1 HOMA-IR 2241:2247 a significantly reduced HOMA-IR 2217:2247 a significantly reduced HOMA-IR in GK rats 2217:2258 Intragastric administration of BT, LM, PD, or BA led to a significantly reduced HOMA-IR in GK rats. 35088787 4 33 theme TB 624:625 arg1 effect 614:619 the effect 610:619 the effect of TB 610:625 This study aimed to determine the effect of TB in treating diabetes and explore the underlying mechanism of action of intestinal microbes by using Goto-Kakizaki (GK) rats. 35088787 10 34 theme characteristic 1796:1809 arg1 flora 1822:1826 the core characteristic intestinal flora 1787:1826 the core characteristic intestinal flora 1787:1826 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 6 35 theme blood 886:890 arg1 glucose 892:898 fasting blood glucose 878:898 fasting blood glucose (FBG) content 878:912 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 6 35 theme blood 886:890 arg1 FBG 901:903 FBG 901:903 FBG 901:903 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 8 36 dep time 1410:1413 arg1 extension 1387:1395 extension 1387:1395 extension 1387:1395 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35088787 8 36 dep time 1410:1413 arg1 the 1383:1385 the 1383:1385 the 1383:1385 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35088787 15 37 theme functional 2742:2751 arg1 component 2758:2766 a functional food component 2740:2766 a functional food component with great potential to treat or prevent diabetes 2740:2816 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 15 37 theme functional 2742:2751 arg1 TB 2734:2735 TB 2734:2735 TB 2734:2735 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 15 38 theme diabetic 2640:2647 arg1 rats 2649:2652 diabetic rats 2640:2652 diabetic rats 2640:2652 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 11 39 theme BT 2192:2193 arg1 administration 2174:2187 Intragastric administration 2161:2187 Intragastric administration of BT, LM, PD, or BA 2161:2208 Intragastric administration of BT, LM, PD, or BA led to a significantly reduced HOMA-IR in GK rats. 35088787 8 40 from number 1420:1425 arg1 rats 1469:1472 GK rats 1466:1472 GK rats 1466:1472 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35088787 10 41 theme Bacteroides 1838:1848 arg1 Bacteroides_acidifaciens 1938:1961 Bacteroides_acidifaciens 1938:1961 Bacteroides_acidifaciens 1938:1961 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 10 41 theme Bacteroides 1838:1848 arg1 BT 1868:1869 BT 1868:1869 BT 1868:1869 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 10 41 theme Bacteroides 1838:1848 arg1 Lactobacillus 1873:1885 Lactobacillus 1873:1885 Lactobacillus 1873:1885 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 10 41 theme Bacteroides 1838:1848 arg1 thetaiotaomicron 1850:1865 Bacteroides thetaiotaomicron 1838:1865 Bacteroides thetaiotaomicron (BT) 1838:1870 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 10 41 theme Bacteroides 1838:1848 arg1 Parabacteroides 1901:1915 Parabacteroides 1901:1915 Parabacteroides 1901:1915 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 0 42 theme Goto-Kakizaki 104:116 arg1 rats 118:121 Goto-Kakizaki rats 104:121 Goto-Kakizaki rats 104:121 Theabrownin-targeted regulation of intestinal microorganisms to improve glucose and lipid metabolism in Goto-Kakizaki rats. 35088787 7 43 theme enzyme 1335:1340 arg1 activities 1342:1351 enzyme activities 1335:1351 enzyme activities 1335:1351 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 11 44 theme PD 2200:2201 arg1 administration 2174:2187 Intragastric administration 2161:2187 Intragastric administration of BT, LM, PD, or BA 2161:2208 Intragastric administration of BT, LM, PD, or BA led to a significantly reduced HOMA-IR in GK rats. 35088787 8 45 from microorganisms 1448:1461 arg1 rats 1469:1472 GK rats 1466:1472 GK rats 1466:1472 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35088787 2 46 theme attached 347:354 arg1 residues 356:363 attached residues 347:363 attached residues 347:363 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 46 theme attached 347:354 arg1 proteins 388:395 proteins 388:395 proteins 388:395 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 46 theme attached 347:354 arg1 polysaccharides 368:382 polysaccharides 368:382 polysaccharides 368:382 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 0 47 theme Theabrownin-targeted 0:19 arg1 regulation 21:30 Theabrownin-targeted regulation 0:30 Theabrownin-targeted regulation of intestinal microorganisms 0:59 Theabrownin-targeted regulation of intestinal microorganisms to improve glucose and lipid metabolism in Goto-Kakizaki rats. 35088787 6 48 theme Homeostatic 919:929 arg1 HOMA-IR 972:978 HOMA-IR 972:978 HOMA-IR 972:978 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 6 48 theme Homeostatic 919:929 arg1 Assessment 937:946 Homeostatic Model Assessment 919:946 Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) 919:979 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 10 49 theme GK 2019:2020 arg1 rats 2022:2025 GK rats 2019:2025 GK rats 2019:2025 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 4 50 theme action 688:693 arg1 mechanism 675:683 the underlying mechanism 660:683 the underlying mechanism of action of intestinal microbes 660:716 This study aimed to determine the effect of TB in treating diabetes and explore the underlying mechanism of action of intestinal microbes by using Goto-Kakizaki (GK) rats. 35088787 5 51 theme Diabetic 752:759 arg1 rats 764:767 Diabetic GK rats 752:767 Diabetic GK rats 752:767 Diabetic GK rats were treated up to 8 weeks with TB (GK-TB). 35088787 7 52 dep lipase 1275:1280 arg1 activities 1342:1351 enzyme activities 1335:1351 enzyme activities 1335:1351 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 5 53 dep 8 788:788 arg1 to 785:786 to 785:786 to 785:786 Diabetic GK rats were treated up to 8 weeks with TB (GK-TB). 35088787 0 54 theme microorganisms 46:59 arg1 regulation 21:30 Theabrownin-targeted regulation 0:30 Theabrownin-targeted regulation of intestinal microorganisms 0:59 Theabrownin-targeted regulation of intestinal microorganisms to improve glucose and lipid metabolism in Goto-Kakizaki rats. 35088787 2 55 with pigment 306:312 arg1 residues 356:363 attached residues 347:363 attached residues 347:363 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 55 with pigment 306:312 arg1 proteins 388:395 proteins 388:395 proteins 388:395 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 55 with pigment 306:312 arg1 polysaccharides 368:382 polysaccharides 368:382 polysaccharides 368:382 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 55 with pigment 306:312 arg1 rings 337:341 multiple aromatic rings 319:341 multiple aromatic rings 319:341 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 7 56 theme P 1354:1354 arg1 > 1356:1356 P > 0.05 1354:1361 P > 0.05 1354:1361 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 15 57 theme targeted 2676:2683 arg1 regulation 2685:2694 the targeted regulation 2672:2694 the targeted regulation of intestinal microorganisms 2672:2723 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 3 58 theme blood 457:461 arg1 FBG 472:474 FBG 472:474 FBG 472:474 TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. 35088787 3 58 theme blood 457:461 arg1 glucose 463:469 fasting blood glucose 449:469 fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet 449:523 TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. 35088787 7 59 theme triglyceride 1309:1320 arg1 lipase 1322:1327 hormone-sensitive triglyceride lipase 1291:1327 hormone-sensitive triglyceride lipase (HSL) 1291:1333 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 59 theme triglyceride 1309:1320 arg1 HSL 1330:1332 HSL 1330:1332 HSL 1330:1332 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 15 60 theme TB 2634:2635 arg1 effect 2624:2629 the effect 2620:2629 the effect of TB on diabetic rats 2620:2652 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 4 61 theme Goto-Kakizaki 727:739 arg1 rats 746:749 Goto-Kakizaki (GK) rats 727:749 Goto-Kakizaki (GK) rats 727:749 This study aimed to determine the effect of TB in treating diabetes and explore the underlying mechanism of action of intestinal microbes by using Goto-Kakizaki (GK) rats. 35088787 10 62 dep Parabacteroides 1901:1915 arg1 distasonis 1917:1926 Parabacteroides distasonis (PD) 1901:1931 Parabacteroides distasonis (PD) 1901:1931 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 12 63 theme serum 2374:2378 arg1 TC 2386:2387 the serum lipid TC 2370:2387 the serum lipid TC 2370:2387 Furthermore, BT significantly reduced serum lipid TG and total cholesterol (TC) and BA significantly reduced the serum lipid TC and low-density lipoprotein (LDL). 35088787 4 64 theme GK 742:743 arg1 rats 746:749 Goto-Kakizaki (GK) rats 727:749 Goto-Kakizaki (GK) rats 727:749 This study aimed to determine the effect of TB in treating diabetes and explore the underlying mechanism of action of intestinal microbes by using Goto-Kakizaki (GK) rats. 35088787 7 65 theme circulating 1081:1091 arg1 Meanwhile 1066:1074 Meanwhile 1066:1074 Meanwhile 1066:1074 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 65 theme circulating 1081:1091 arg1 ADPN 1106:1109 ADPN 1106:1109 ADPN 1106:1109 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 65 theme circulating 1081:1091 arg1 adiponectin 1093:1103 the circulating adiponectin 1077:1103 the circulating adiponectin (ADPN) 1077:1110 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 10 66 theme multiple 1702:1709 arg1 technologies 1717:1728 multiple omics technologies 1702:1728 multiple omics technologies 1702:1728 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 2 67 theme multiple 319:326 arg1 rings 337:341 multiple aromatic rings 319:341 multiple aromatic rings 319:341 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 10 68 theme kinase 2057:2062 arg1 pathway 2074:2080 the AMP-activated protein kinase signaling pathway 2031:2080 the AMP-activated protein kinase signaling pathway 2031:2080 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 6 69 theme Insulin 952:958 arg1 Resistance 960:969 Insulin Resistance 952:969 Insulin Resistance 952:969 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 12 70 theme lipid 2305:2309 arg1 TG 2311:2312 serum lipid TG 2299:2312 serum lipid TG 2299:2312 Furthermore, BT significantly reduced serum lipid TG and total cholesterol (TC) and BA significantly reduced the serum lipid TC and low-density lipoprotein (LDL). 35088787 2 71 theme Pu-erh 276:281 arg1 tea 283:285 Pu-erh tea 276:285 Pu-erh tea 276:285 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 8 72 theme intestinal 1437:1446 arg1 microorganisms 1448:1461 unique intestinal microorganisms 1430:1461 unique intestinal microorganisms in GK rats 1430:1472 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35088787 7 73 theme little 1246:1251 arg1 difference 1253:1262 little difference 1246:1262 little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities 1246:1351 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 10 74 theme AMP-activated 2035:2047 arg1 pathway 2074:2080 the AMP-activated protein kinase signaling pathway 2031:2080 the AMP-activated protein kinase signaling pathway 2031:2080 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 2 75 theme pigments 264:271 arg1 one 228:230 one 228:230 one 228:230 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 75 theme pigments 264:271 arg1 pigments 264:271 the most active and abundant pigments 235:271 the most active and abundant pigments in Pu-erh tea 235:285 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 13 76 theme serum 2449:2453 arg1 LDL 2455:2457 serum LDL 2449:2457 serum LDL 2449:2457 PD significantly reduced serum LDL, while the effect of LM was not significant. 35088787 10 77 theme insulin 2083:2089 arg1 pathway 2101:2107 insulin signaling pathway 2083:2107 insulin signaling pathway 2083:2107 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 7 78 from adiponectin 1093:1103 arg1 serum 1151:1155 the serum 1147:1155 the serum of the GK-TB group 1147:1174 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 10 79 theme technologies 1717:1728 arg1 use 1695:1697 The use 1691:1697 The use of multiple omics technologies 1691:1728 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 1 80 theme glucose 188:194 arg1 metabolism 196:205 glucose metabolism 188:205 glucose metabolism 188:205 Diabetes is a disease that is characterized by a disturbance of glucose metabolism. 35088787 6 81 theme TG 865:866 arg1 content 869:875 triglyceride (TG) content 851:875 triglyceride (TG) content 851:875 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 15 82 theme intestinal 2699:2708 arg1 microorganisms 2710:2723 intestinal microorganisms 2699:2723 intestinal microorganisms 2699:2723 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 10 83 dep Lactobacillus 1873:1885 arg1 murinus 1887:1893 Lactobacillus murinus (LM) 1873:1898 Lactobacillus murinus (LM) 1873:1898 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 6 84 theme GK-TB 1013:1017 arg1 group 1019:1023 the GK-TB group 1009:1023 the GK-TB group 1009:1023 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 5 85 theme GK 761:762 arg1 rats 764:767 Diabetic GK rats 752:767 Diabetic GK rats 752:767 Diabetic GK rats were treated up to 8 weeks with TB (GK-TB). 35088787 7 86 from difference 1253:1262 arg1 lipase 1322:1327 hormone-sensitive triglyceride lipase 1291:1327 hormone-sensitive triglyceride lipase (HSL) 1291:1333 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 86 from difference 1253:1262 arg1 HL 1283:1284 HL 1283:1284 HL 1283:1284 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 86 from difference 1253:1262 arg1 lipase 1275:1280 hepatic lipase 1267:1280 hepatic lipase (HL) 1267:1285 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 86 from difference 1253:1262 arg1 HSL 1330:1332 HSL 1330:1332 HSL 1330:1332 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 6 87 theme triglyceride 851:862 arg1 content 869:875 triglyceride (TG) content 851:875 triglyceride (TG) content 851:875 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 10 88 theme bile 2110:2113 arg1 secretion 2115:2123 bile secretion 2110:2123 bile secretion 2110:2123 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 2 89 theme brown 300:304 arg1 pigment 306:312 a brown pigment 298:312 a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins 298:395 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 89 theme brown 300:304 arg1 it 292:293 it 292:293 it 292:293 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 3 90 theme underlying 534:543 arg1 mechanism 545:553 the underlying mechanism 530:553 the underlying mechanism 530:553 TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. 35088787 11 91 theme BA 2207:2208 arg1 administration 2174:2187 Intragastric administration 2161:2187 Intragastric administration of BT, LM, PD, or BA 2161:2208 Intragastric administration of BT, LM, PD, or BA led to a significantly reduced HOMA-IR in GK rats. 35088787 10 92 theme targeted 1764:1771 arg1 regulation 1773:1782 the targeted regulation 1760:1782 the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism 1760:2158 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 15 93 theme great 2773:2777 arg1 potential 2779:2787 great potential 2773:2787 great potential 2773:2787 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 7 94 theme GK-TB 1164:1168 arg1 group 1170:1174 the GK-TB group 1160:1174 the GK-TB group 1160:1174 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 10 95 theme glucose 1987:1993 arg1 metabolism 2005:2014 the glucose and lipid metabolism 1983:2014 metabolism 2005:2014 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 10 96 theme intestinal 1811:1820 arg1 flora 1822:1826 the core characteristic intestinal flora 1787:1826 the core characteristic intestinal flora 1787:1826 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 0 97 theme lipid 84:88 arg1 metabolism 90:99 lipid metabolism 84:99 lipid metabolism 84:99 Theabrownin-targeted regulation of intestinal microorganisms to improve glucose and lipid metabolism in Goto-Kakizaki rats. 35088787 6 98 theme glucose 892:898 arg1 content 906:912 fasting blood glucose (FBG) content 878:912 fasting blood glucose (FBG) content 878:912 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 11 99 theme GK 2252:2253 arg1 rats 2255:2258 GK rats 2252:2258 GK rats 2252:2258 Intragastric administration of BT, LM, PD, or BA led to a significantly reduced HOMA-IR in GK rats. 35088787 6 100 theme control 1040:1046 arg1 group 1048:1052 the GK control group 1033:1052 the GK control group (P < 0.05) 1033:1063 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 6 100 theme control 1040:1046 arg1 < 1057:1057 P < 0.05 1055:1062 P < 0.05 1055:1062 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 3 101 from properties 486:495 arg1 rats 500:503 rats 500:503 rats fed a high-fat diet 500:523 TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. 35088787 10 102 theme core 1791:1794 arg1 flora 1822:1826 the core characteristic intestinal flora 1787:1826 the core characteristic intestinal flora 1787:1826 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 6 103 theme fasting 878:884 arg1 glucose 892:898 fasting blood glucose 878:898 fasting blood glucose (FBG) content 878:912 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 6 103 theme fasting 878:884 arg1 FBG 901:903 FBG 901:903 FBG 901:903 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 11 104 theme Intragastric 2161:2172 arg1 administration 2174:2187 Intragastric administration 2161:2187 Intragastric administration of BT, LM, PD, or BA 2161:2208 Intragastric administration of BT, LM, PD, or BA led to a significantly reduced HOMA-IR in GK rats. 35088787 15 105 from effect 2624:2629 arg1 rats 2649:2652 diabetic rats 2640:2652 diabetic rats 2640:2652 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 0 106 from glucose 72:78 arg1 rats 118:121 Goto-Kakizaki rats 104:121 Goto-Kakizaki rats 104:121 Theabrownin-targeted regulation of intestinal microorganisms to improve glucose and lipid metabolism in Goto-Kakizaki rats. 35088787 10 107 theme lipid 1999:2003 arg1 metabolism 2005:2014 the glucose and lipid metabolism 1983:2014 metabolism 2005:2014 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 9 108 theme Firmicutes/Bacteroides 1561:1582 arg1 ratio 1584:1588 The Firmicutes/Bacteroides ratio 1557:1588 The Firmicutes/Bacteroides ratio 1557:1588 The Firmicutes/Bacteroides ratio was decreased significantly, and the composition of Actinobacteria and Proteobacteria was increased. 35088787 4 109 theme microbes 709:716 arg1 action 688:693 action 688:693 action of intestinal microbes 688:716 This study aimed to determine the effect of TB in treating diabetes and explore the underlying mechanism of action of intestinal microbes by using Goto-Kakizaki (GK) rats. 35088787 6 110 theme Model 931:935 arg1 HOMA-IR 972:978 HOMA-IR 972:978 HOMA-IR 972:978 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 6 110 theme Model 931:935 arg1 Assessment 937:946 Homeostatic Model Assessment 919:946 Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) 919:979 Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group (P < 0.05). 35088787 10 111 theme rats 2022:2025 arg1 metabolism 2005:2014 the glucose and lipid metabolism 1983:2014 metabolism 2005:2014 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 4 112 theme underlying 664:673 arg1 mechanism 675:683 the underlying mechanism 660:683 the underlying mechanism of action of intestinal microbes 660:716 This study aimed to determine the effect of TB in treating diabetes and explore the underlying mechanism of action of intestinal microbes by using Goto-Kakizaki (GK) rats. 35088787 0 113 theme intestinal 35:44 arg1 microorganisms 46:59 intestinal microorganisms 35:59 intestinal microorganisms 35:59 Theabrownin-targeted regulation of intestinal microorganisms to improve glucose and lipid metabolism in Goto-Kakizaki rats. 35088787 2 114 theme proteins 388:395 arg1 residues 356:363 attached residues 347:363 attached residues 347:363 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 114 theme proteins 388:395 arg1 proteins 388:395 proteins 388:395 proteins 388:395 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 114 theme proteins 388:395 arg1 polysaccharides 368:382 polysaccharides 368:382 polysaccharides 368:382 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 114 theme proteins 388:395 arg1 rings 337:341 multiple aromatic rings 319:341 multiple aromatic rings 319:341 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 12 115 theme total 2318:2322 arg1 TC 2337:2338 TC 2337:2338 TC 2337:2338 Furthermore, BT significantly reduced serum lipid TG and total cholesterol (TC) and BA significantly reduced the serum lipid TC and low-density lipoprotein (LDL). 35088787 12 115 theme total 2318:2322 arg1 cholesterol 2324:2334 total cholesterol 2318:2334 total cholesterol (TC) 2318:2339 Furthermore, BT significantly reduced serum lipid TG and total cholesterol (TC) and BA significantly reduced the serum lipid TC and low-density lipoprotein (LDL). 35088787 8 116 from rats 1469:1472 arg1 number 1420:1425 the number 1416:1425 the number of unique intestinal microorganisms in GK rats 1416:1472 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35088787 2 117 theme polysaccharides 368:382 arg1 residues 356:363 attached residues 347:363 attached residues 347:363 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 117 theme polysaccharides 368:382 arg1 proteins 388:395 proteins 388:395 proteins 388:395 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 117 theme polysaccharides 368:382 arg1 polysaccharides 368:382 polysaccharides 368:382 polysaccharides 368:382 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 2 117 theme polysaccharides 368:382 arg1 rings 337:341 multiple aromatic rings 319:341 multiple aromatic rings 319:341 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 7 118 dep was 1242:1244 arg1 > 1356:1356 P > 0.05 1354:1361 P > 0.05 1354:1361 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 119 from leptin 1113:1118 arg1 serum 1151:1155 the serum 1147:1155 the serum of the GK-TB group 1147:1174 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 2 120 theme aromatic 328:335 arg1 rings 337:341 multiple aromatic rings 319:341 multiple aromatic rings 319:341 Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. 35088787 3 121 theme glucose 463:469 arg1 properties 486:495 fasting blood glucose (FBG)-lowering properties 449:495 fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet 449:523 TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. 35088787 13 122 theme LM 2480:2481 arg1 effect 2470:2475 the effect 2466:2475 the effect of LM 2466:2481 PD significantly reduced serum LDL, while the effect of LM was not significant. 35088787 13 122 theme LM 2480:2481 arg1 significant 2491:2501 significant 2491:2501 significant 2491:2501 PD significantly reduced serum LDL, while the effect of LM was not significant. 35088787 7 123 theme hormone-sensitive 1291:1307 arg1 lipase 1322:1327 hormone-sensitive triglyceride lipase 1291:1327 hormone-sensitive triglyceride lipase (HSL) 1291:1333 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 7 123 theme hormone-sensitive 1291:1307 arg1 HSL 1330:1332 HSL 1330:1332 HSL 1330:1332 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 15 124 theme food 2753:2756 arg1 component 2758:2766 a functional food component 2740:2766 a functional food component with great potential to treat or prevent diabetes 2740:2816 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 15 124 theme food 2753:2756 arg1 TB 2734:2735 TB 2734:2735 TB 2734:2735 Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes. 35088787 9 125 theme Actinobacteria 1642:1655 arg1 composition 1627:1637 the composition 1623:1637 the composition of Actinobacteria and Proteobacteria 1623:1674 The Firmicutes/Bacteroides ratio was decreased significantly, and the composition of Actinobacteria and Proteobacteria was increased. 35088787 3 126 theme fasting 449:455 arg1 FBG 472:474 FBG 472:474 FBG 472:474 TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. 35088787 3 126 theme fasting 449:455 arg1 glucose 463:469 fasting blood glucose 449:469 fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet 449:523 TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. 35088787 7 127 from levels 1137:1142 arg1 serum 1151:1155 the serum 1147:1155 the serum of the GK-TB group 1147:1174 Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities (P > 0.05). 35088787 9 128 theme Proteobacteria 1661:1674 arg1 composition 1627:1637 the composition 1623:1637 the composition of Actinobacteria and Proteobacteria 1623:1674 The Firmicutes/Bacteroides ratio was decreased significantly, and the composition of Actinobacteria and Proteobacteria was increased. 35088787 10 129 theme omics 1711:1715 arg1 technologies 1717:1728 multiple omics technologies 1702:1728 multiple omics technologies 1702:1728 The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides_acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. 35088787 3 130 theme -lowering 476:484 arg1 properties 486:495 fasting blood glucose (FBG)-lowering properties 449:495 fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet 449:523 TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. 35088787 8 131 theme unique 1430:1435 arg1 microorganisms 1448:1461 unique intestinal microorganisms 1430:1461 unique intestinal microorganisms in GK rats 1430:1472 Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. 35408506 8 0 theme ileum 1585:1589 arg1 tissues 1591:1597 A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues 1535:1597 A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues 1535:1597 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 2 1 theme in 340:341 arg1 test 362:365 the in vivo antidiarrheal test 336:365 the in vivo antidiarrheal test 336:365 The phytochemicals were detected using gas chromatography-mass spectrometry (GC-MS) while the in vivo antidiarrheal test was done using Swiss albino mice. 35408506 9 2 from use 2112:2114 arg1 disorders 2173:2181 diarrheal and hyperactive gut motility disorders 2134:2181 diarrheal and hyperactive gut motility disorders 2134:2181 Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders. 35408506 1 3 theme extract 237:243 arg1 part 202:205 the fruit part 192:205 the fruit part of Acacia nilotica methanolic extract 192:243 This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. 35408506 8 4 theme peaks 1958:1962 arg1 suppression 1931:1941 suppression 1931:1941 suppression of the maximum peaks, similar to verapamil, used as standard CCB 1931:2006 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 8 5 theme inhibitory-like 1452:1466 arg1 effects 1468:1474 The dual inhibitory-like effects 1443:1474 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ 1443:1505 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 9 6 theme nilotica 2122:2129 arg1 use 2112:2114 medicinal use 2102:2114 medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders 2102:2181 Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders. 35408506 5 7 theme antidiarrheal 800:812 arg1 experiment 814:823 the antidiarrheal experiment 796:823 the antidiarrheal experiment 796:823 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 7 8 theme K+ 1270:1271 arg1 spasms 1288:1293 increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms 1191:1293 increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues 1191:1310 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 8 9 theme relaxation 1636:1645 arg1 curves 1647:1652 isoprenaline relaxation curves 1623:1652 isoprenaline relaxation curves 1623:1652 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 9 10 theme diarrheal 2134:2142 arg1 disorders 2173:2181 diarrheal and hyperactive gut motility disorders 2134:2181 diarrheal and hyperactive gut motility disorders 2134:2181 Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders. 35408506 5 11 from mg/kg 936:940 arg1 protection 910:919 40% protection 906:919 40% protection of mice at 200 mg/kg 906:940 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 1 12 theme medicinal 175:183 arg1 use 185:187 the medicinal use 171:187 the medicinal use of the fruit part of Acacia nilotica methanolic extract 171:243 This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. 35408506 7 13 theme enzyme 1411:1416 arg1 inhibitor 1376:1384 a dual inhibitor 1369:1384 a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels 1369:1440 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 13 theme enzyme 1411:1416 arg1 papaverine 1357:1366 papaverine 1357:1366 papaverine 1357:1366 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 14 theme carbachol 1239:1247 arg1 spasms 1288:1293 increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms 1191:1293 increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues 1191:1310 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 2 15 theme albino 388:393 arg1 mice 395:398 Swiss albino mice 382:398 Swiss albino mice 382:398 The phytochemicals were detected using gas chromatography-mass spectrometry (GC-MS) while the in vivo antidiarrheal test was done using Swiss albino mice. 35408506 3 16 theme different 520:528 arg1 assays 538:543 different ex vivo assays 520:543 different ex vivo assays 520:543 To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. 35408506 8 17 theme similar 1965:1971 arg1 peaks 1958:1962 the maximum peaks 1946:1962 the maximum peaks 1946:1962 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 0 18 theme nilotica 115:122 arg1 Extract 97:103 the Methanolic Extract 82:103 the Methanolic Extract of Acacia nilotica 82:122 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 8 19 theme CCB-like 1771:1778 arg1 effect 1780:1785 its CCB-like effect 1767:1785 its CCB-like effect of the extract 1767:1800 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 1 20 theme fruit 196:200 arg1 part 202:205 the fruit part 192:205 the fruit part of Acacia nilotica methanolic extract 192:243 This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. 35408506 5 21 theme % 951:951 arg1 protection 953:962 80% protection 949:962 80% protection 949:962 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 7 22 theme concentrations 1202:1215 arg1 spasms 1288:1293 increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms 1191:1293 increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues 1191:1310 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 4 23 theme major 655:659 arg1 polyphenol 661:670 the major polyphenol 651:670 the major polyphenol present (64.04%) in addition to polysaccharides 651:718 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 4 23 theme major 655:659 arg1 pyrogallol 637:646 pyrogallol 637:646 pyrogallol 637:646 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 0 24 theme Antidiarrheal 39:51 arg1 Effects 71:77 In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects 19:77 In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica 19:122 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 5 25 theme administered 1004:1015 arg1 extract 1017:1023 the orally administered extract 993:1023 the orally administered extract 993:1023 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 1 26 theme present 130:136 arg1 study 138:142 This present study 125:142 This present study 125:142 This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. 35408506 4 27 theme present 672:678 arg1 polyphenol 661:670 the major polyphenol 651:670 the major polyphenol present (64.04%) in addition to polysaccharides 651:718 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 4 27 theme present 672:678 arg1 pyrogallol 637:646 pyrogallol 637:646 pyrogallol 637:646 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 0 28 theme Antispasmodic 57:69 arg1 Effects 71:77 In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects 19:77 In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica 19:122 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 5 29 theme diarrheal 848:856 arg1 episodes 858:865 diarrheal episodes 848:865 diarrheal episodes in mice 848:873 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 4 30 theme amino 733:737 arg1 acid 739:742 amino acid 733:742 amino acid 733:742 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 2 31 theme Swiss 382:386 arg1 mice 395:398 Swiss albino mice 382:398 Swiss albino mice 382:398 The phytochemicals were detected using gas chromatography-mass spectrometry (GC-MS) while the in vivo antidiarrheal test was done using Swiss albino mice. 35408506 0 32 theme Methanolic 86:95 arg1 Extract 97:103 the Methanolic Extract 82:103 the Methanolic Extract of Acacia nilotica 82:122 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 5 33 theme 40 906:907 arg1 % 908:908 % 908:908 % 908:908 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 7 34 theme Ca++ 1428:1431 arg1 channels 1433:1440 Ca++ channels 1428:1440 Ca++ channels 1428:1440 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 35 theme increasing 1191:1200 arg1 mg/mL 1228:1232 0.3 to 10 mg/mL 1218:1232 0.3 to 10 mg/mL 1218:1232 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 35 theme increasing 1191:1200 arg1 concentrations 1202:1215 increasing concentrations 1191:1215 increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues 1191:1310 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 8 36 theme maximum 1950:1956 arg1 peaks 1958:1962 the maximum peaks 1946:1962 the maximum peaks 1946:1962 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 0 37 theme GC-MS 0:4 arg1 Analysis 6:13 GC-MS Analysis 0:13 GC-MS Analysis 0:13 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 5 38 from episodes 858:865 arg1 mice 870:873 mice 870:873 mice 870:873 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 8 39 theme standard 1995:2002 arg1 CCB 2004:2006 standard CCB 1995:2006 standard CCB 1995:2006 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 5 40 dep A. 826:827 arg1 nilotica 829:836 A. nilotica 826:836 A. nilotica 826:836 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 9 41 theme hyperactive 2148:2158 arg1 disorders 2173:2181 diarrheal and hyperactive gut motility disorders 2134:2181 diarrheal and hyperactive gut motility disorders 2134:2181 Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders. 35408506 4 42 theme acid 761:764 arg1 pyrogallol 637:646 pyrogallol 637:646 pyrogallol 637:646 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 4 42 theme acid 761:764 arg1 esters 766:771 fatty acid esters 755:771 fatty acid esters 755:771 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 7 43 dep 10 1225:1226 arg1 to 1222:1223 to 1222:1223 to 1222:1223 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 44 theme equal 1315:1319 arg1 potencies 1321:1329 equal potencies 1315:1329 equal potencies (p > 0.05) 1315:1343 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 44 theme equal 1315:1319 arg1 p 1332:1332 p > 0.05 1332:1342 p > 0.05 1332:1342 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 0 45 dep Ex 31:32 arg1 Vivo 34:37 Vivo 34:37 Vivo 34:37 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 8 46 theme PDE 1729:1731 arg1 mechanism 1749:1757 the PDE inhibitory-like mechanism 1725:1757 the PDE inhibitory-like mechanism 1725:1757 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 9 47 theme chemical 2044:2051 arg1 composition 2053:2063 the chemical composition 2040:2063 the chemical composition 2040:2063 Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders. 35408506 0 48 theme Ex 31:32 arg1 Effects 71:77 In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects 19:77 In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica 19:122 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 8 49 theme non-specific 1836:1847 arg1 inhibition 1849:1858 non-specific inhibition 1836:1858 non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB 1836:2006 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 8 50 from effects 1468:1474 arg1 Ca++ 1502:1505 Ca++ 1502:1505 Ca++ 1502:1505 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 8 50 from effects 1468:1474 arg1 PDE 1494:1496 PDE 1494:1496 PDE 1494:1496 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 1 51 theme part 202:205 arg1 use 185:187 the medicinal use 171:187 the medicinal use of the fruit part of Acacia nilotica methanolic extract 171:243 This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. 35408506 4 52 contain contained 627:635 arg2 esters 766:771 fatty acid esters 755:771 fatty acid esters 755:771 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 4 52 contain contained 627:635 arg2 polyphenol 661:670 the major polyphenol 651:670 the major polyphenol present (64.04%) in addition to polysaccharides 651:718 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 4 52 contain contained 627:635 arg1 A. 615:616 A. 615:616 A. 615:616 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 4 52 contain contained 627:635 arg2 triterpenoids 778:790 triterpenoids 778:790 triterpenoids 778:790 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 4 52 contain contained 627:635 arg2 steroids 745:752 steroids 745:752 steroids 745:752 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 4 52 contain contained 627:635 arg2 pyrogallol 637:646 pyrogallol 637:646 pyrogallol 637:646 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 9 53 theme mechanistic 2078:2088 arg1 support 2090:2096 mechanistic support 2078:2096 mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders 2078:2181 Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders. 35408506 1 54 theme Acacia 210:215 arg1 extract 237:243 Acacia nilotica methanolic extract 210:243 Acacia nilotica methanolic extract 210:243 This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. 35408506 7 55 theme -evoked 1280:1286 arg1 spasms 1288:1293 increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms 1191:1293 increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues 1191:1310 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 5 56 theme mice 924:927 arg1 protection 910:919 40% protection 906:919 40% protection of mice at 200 mg/kg 906:940 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 8 57 theme concentration 1878:1890 arg1 curves 1901:1906 CaCl2-mediated concentration response curves 1863:1906 CaCl2-mediated concentration response curves 1863:1906 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 3 58 theme antispasmodic 462:474 arg1 effect 476:481 the antispasmodic effect 458:481 the antispasmodic effect 458:481 To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. 35408506 1 59 theme methanolic 226:235 arg1 extract 237:243 Acacia nilotica methanolic extract 210:243 Acacia nilotica methanolic extract 210:243 This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. 35408506 8 60 theme curves 1901:1906 arg1 inhibition 1849:1858 non-specific inhibition 1836:1858 non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB 1836:2006 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 7 61 dep CCh 1250:1252 arg1 µM 1257:1258 1 µM 1255:1258 1 µM 1255:1258 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 8 62 theme isoprenaline 1623:1634 arg1 curves 1647:1652 isoprenaline relaxation curves 1623:1652 isoprenaline relaxation curves 1623:1652 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 3 63 theme rat 493:495 arg1 ileum 497:501 isolated rat ileum 484:501 isolated rat ileum 484:501 To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. 35408506 8 64 theme dual 1447:1450 arg1 effects 1468:1474 The dual inhibitory-like effects 1443:1474 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ 1443:1505 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 5 65 located observed 968:975 arg1 mg/kg 984:988 400 mg/kg 980:988 400 mg/kg 980:988 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 5 65 located observed 968:975 arg2 protection 953:962 80% protection 949:962 80% protection 949:962 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 7 66 theme high 1265:1268 arg1 K+ 1270:1271 high K+ 1265:1271 high K+ (80 mM) 1265:1279 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 66 theme high 1265:1268 arg1 mM 1277:1278 80 mM 1274:1278 80 mM 1274:1278 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 6 67 theme control 1113:1119 arg1 drug 1121:1124 a control drug 1111:1124 a control drug 1111:1124 The highest antidiarrheal effect was observed with loperamide (p < 0.01), used as a control drug. 35408506 3 68 theme ex 530:531 arg1 assays 538:543 different ex vivo assays 520:543 different ex vivo assays 520:543 To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. 35408506 7 69 theme phosphodiesterase 1393:1409 arg1 PDE 1419:1421 PDE 1419:1421 PDE 1419:1421 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 69 theme phosphodiesterase 1393:1409 arg1 enzyme 1411:1416 the phosphodiesterase enzyme 1389:1416 the phosphodiesterase enzyme (PDE) 1389:1422 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 0 70 theme Acacia 108:113 arg1 nilotica 115:122 Acacia nilotica 108:122 Acacia nilotica 108:122 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 2 71 theme chromatography-mass 289:307 arg1 GC-MS 323:327 GC-MS 323:327 GC-MS 323:327 The phytochemicals were detected using gas chromatography-mass spectrometry (GC-MS) while the in vivo antidiarrheal test was done using Swiss albino mice. 35408506 2 71 theme chromatography-mass 289:307 arg1 spectrometry 309:320 gas chromatography-mass spectrometry 285:320 gas chromatography-mass spectrometry (GC-MS) 285:328 The phytochemicals were detected using gas chromatography-mass spectrometry (GC-MS) while the in vivo antidiarrheal test was done using Swiss albino mice. 35408506 6 72 theme highest 1030:1036 arg1 effect 1052:1057 The highest antidiarrheal effect 1026:1057 The highest antidiarrheal effect 1026:1057 The highest antidiarrheal effect was observed with loperamide (p < 0.01), used as a control drug. 35408506 8 73 theme nilotica 1482:1489 arg1 effects 1468:1474 The dual inhibitory-like effects 1443:1474 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ 1443:1505 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 9 74 theme gut 2160:2162 arg1 disorders 2173:2181 diarrheal and hyperactive gut motility disorders 2134:2181 diarrheal and hyperactive gut motility disorders 2134:2181 Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders. 35408506 7 75 theme dual 1371:1374 arg1 inhibitor 1376:1384 a dual inhibitor 1369:1384 a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels 1369:1440 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 75 theme dual 1371:1374 arg1 papaverine 1357:1366 papaverine 1357:1366 papaverine 1357:1366 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 8 76 theme -pre-incubated 1570:1583 arg1 tissues 1591:1597 A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues 1535:1597 A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues 1535:1597 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 7 77 from spasms 1288:1293 arg1 tissues 1304:1310 ileum tissues 1298:1310 ileum tissues 1298:1310 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 8 78 theme lower 1662:1666 arg1 doses 1668:1672 lower doses 1662:1672 lower doses (leftward) 1662:1683 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 8 78 theme lower 1662:1666 arg1 leftward 1675:1682 leftward 1675:1682 leftward 1675:1682 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 8 79 theme similar 1686:1692 arg1 curves 1647:1652 isoprenaline relaxation curves 1623:1652 isoprenaline relaxation curves 1623:1652 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 5 80 theme 80 949:950 arg1 % 951:951 % 951:951 % 951:951 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 6 81 theme antidiarrheal 1038:1050 arg1 effect 1052:1057 The highest antidiarrheal effect 1026:1057 The highest antidiarrheal effect 1026:1057 The highest antidiarrheal effect was observed with loperamide (p < 0.01), used as a control drug. 35408506 3 82 theme physiological 562:574 arg1 environment 576:586 a physiological environment 560:586 a physiological environment 560:586 To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. 35408506 8 83 theme A. 1535:1536 arg1 mg/mL 1564:1568 1 and 3 mg/mL 1556:1568 1 and 3 mg/mL 1556:1568 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 8 83 theme A. 1535:1536 arg1 extract 1547:1553 A. nilotica extract 1535:1553 A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues 1535:1597 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 3 84 dep ex 530:531 arg1 vivo 533:536 vivo 533:536 vivo 533:536 To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. 35408506 0 85 dep In 19:20 arg1 Vivo 22:25 Vivo 22:25 Vivo 22:25 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 8 86 theme extract 1547:1553 arg1 tissues 1591:1597 A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues 1535:1597 A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues 1535:1597 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 4 87 dep present 672:678 arg1 % 686:686 64.04% 681:686 64.04% 681:686 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 2 88 theme gas 285:287 arg1 GC-MS 323:327 GC-MS 323:327 GC-MS 323:327 The phytochemicals were detected using gas chromatography-mass spectrometry (GC-MS) while the in vivo antidiarrheal test was done using Swiss albino mice. 35408506 2 88 theme gas 285:287 arg1 spectrometry 309:320 gas chromatography-mass spectrometry 285:320 gas chromatography-mass spectrometry (GC-MS) 285:328 The phytochemicals were detected using gas chromatography-mass spectrometry (GC-MS) while the in vivo antidiarrheal test was done using Swiss albino mice. 35408506 2 89 dep in 340:341 arg1 vivo 343:346 vivo 343:346 vivo 343:346 The phytochemicals were detected using gas chromatography-mass spectrometry (GC-MS) while the in vivo antidiarrheal test was done using Swiss albino mice. 35408506 5 90 dep significantly 875:887 arg1 p 890:890 p 890:890 p < 0.05 890:900 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 0 91 theme Extract 97:103 arg1 Effects 71:77 In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects 19:77 In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica 19:122 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 0 91 theme Extract 97:103 arg1 Analysis 6:13 GC-MS Analysis 0:13 GC-MS Analysis 0:13 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 7 92 dep ex 1134:1135 arg1 vivo 1137:1140 vivo 1137:1140 vivo 1137:1140 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 8 93 theme inhibitory-like 1733:1747 arg1 mechanism 1749:1757 the PDE inhibitory-like mechanism 1725:1757 the PDE inhibitory-like mechanism 1725:1757 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 7 94 theme channels 1433:1440 arg1 inhibitor 1376:1384 a dual inhibitor 1369:1384 a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels 1369:1440 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 94 theme channels 1433:1440 arg1 papaverine 1357:1366 papaverine 1357:1366 papaverine 1357:1366 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 0 95 theme In 19:20 arg1 Effects 71:77 In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects 19:77 In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica 19:122 GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica. 35408506 8 96 with right 1920:1924 arg1 suppression 1931:1941 suppression 1931:1941 suppression of the maximum peaks, similar to verapamil, used as standard CCB 1931:2006 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 3 97 theme s 443:443 arg1 details 418:424 the details 414:424 the details of the mechanism(s) involved in the antispasmodic effect 414:481 To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. 35408506 4 98 dep A. 615:616 arg1 nilotica 618:625 A. nilotica 615:625 A. nilotica 615:625 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 4 99 theme fatty 755:759 arg1 pyrogallol 637:646 pyrogallol 637:646 pyrogallol 637:646 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 4 99 theme fatty 755:759 arg1 esters 766:771 fatty acid esters 755:771 fatty acid esters 755:771 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 3 100 theme mechanism 433:441 arg1 s 443:443 the mechanism(s) 429:444 the mechanism(s) involved in the antispasmodic effect 429:481 To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. 35408506 8 101 theme extract 1794:1800 arg1 effect 1780:1785 its CCB-like effect 1767:1785 its CCB-like effect of the extract 1767:1800 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 7 102 theme ex 1134:1135 arg1 experiments 1142:1152 the ex vivo experiments 1130:1152 the ex vivo experiments 1130:1152 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 5 103 theme % 908:908 arg1 protection 910:919 40% protection 906:919 40% protection of mice at 200 mg/kg 906:940 In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. 35408506 9 104 theme motility 2164:2171 arg1 disorders 2173:2181 diarrheal and hyperactive gut motility disorders 2134:2181 diarrheal and hyperactive gut motility disorders 2134:2181 Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders. 35408506 8 105 theme CaCl2-mediated 1863:1876 arg1 curves 1901:1906 CaCl2-mediated concentration response curves 1863:1906 CaCl2-mediated concentration response curves 1863:1906 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 8 106 dep A. 1535:1536 arg1 nilotica 1538:1545 nilotica 1538:1545 nilotica 1538:1545 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 2 107 theme antidiarrheal 348:360 arg1 test 362:365 the in vivo antidiarrheal test 336:365 the in vivo antidiarrheal test 336:365 The phytochemicals were detected using gas chromatography-mass spectrometry (GC-MS) while the in vivo antidiarrheal test was done using Swiss albino mice. 35408506 9 108 theme medicinal 2102:2110 arg1 use 2112:2114 medicinal use 2102:2114 medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders 2102:2181 Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders. 35408506 7 109 theme ileum 1298:1302 arg1 tissues 1304:1310 ileum tissues 1298:1310 ileum tissues 1298:1310 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 7 110 dep A. 1155:1156 arg1 nilotica 1158:1165 A. nilotica 1155:1165 A. nilotica 1155:1165 In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. 35408506 8 111 theme response 1892:1899 arg1 curves 1901:1906 CaCl2-mediated concentration response curves 1863:1906 CaCl2-mediated concentration response curves 1863:1906 The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. 35408506 4 112 theme GC-MS 589:593 arg1 results 595:601 GC-MS results 589:601 GC-MS results 589:601 GC-MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. 35408506 3 113 theme isolated 484:491 arg1 ileum 497:501 isolated rat ileum 484:501 isolated rat ileum 484:501 To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. 35408506 1 114 theme nilotica 217:224 arg1 extract 237:243 Acacia nilotica methanolic extract 210:243 Acacia nilotica methanolic extract 210:243 This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. 37112819 5 0 theme additional 718:727 arg1 N-glycosylation 729:743 additional N-glycosylation 718:743 additional N-glycosylation 718:743 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 0 1 from Insertion 8:16 arg1 Protein 51:57 the Hepatitis B Virus Surface Protein 21:57 the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation 21:87 A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape. 37112819 1 2 theme virus 146:150 arg1 infection 158:166 Chronic hepatitis B virus (HBV) infection 126:166 Chronic hepatitis B virus (HBV) infection 126:166 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 1 2 theme virus 146:150 arg1 threat 187:192 a global health threat 171:192 a global health threat 171:192 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 9 3 theme novel 1296:1300 arg1 insertion 1317:1325 the novel six-nucleotide insertion 1292:1325 the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations 1292:1448 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 9 4 theme breakthrough 1529:1540 arg1 infection 1542:1550 breakthrough infection 1529:1550 breakthrough infection by evasion of vaccine-induced immunity 1529:1589 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 7 5 gly hyperglycosylated 1084:1100 arg1 variant 1112:1118 the hyperglycosylated insertion variant 1080:1118 the hyperglycosylated insertion variant 1080:1118 Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. 37112819 5 6 theme antigenic 682:690 arg1 loop 692:695 the antigenic loop 678:695 the antigenic loop of HBsAg 678:704 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 3 7 from HBsAg 366:370 arg1 parallel 375:382 parallel 375:382 parallel with anti-HBs 375:396 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 7 8 theme hyperglycosylated 1084:1100 arg1 variant 1112:1118 the hyperglycosylated insertion variant 1080:1118 the hyperglycosylated insertion variant 1080:1118 Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. 37112819 9 9 theme vaccine-induced 1566:1580 arg1 immunity 1582:1589 vaccine-induced immunity 1566:1589 vaccine-induced immunity 1566:1589 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 3 10 theme detectable 341:350 arg1 HBsAg 366:370 detectable but low-level HBsAg 341:370 detectable but low-level HBsAg in parallel with anti-HBs 341:396 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 3 11 theme positive 316:323 arg1 patient 308:314 A patient 306:314 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs 306:396 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 4 12 link serum-derived 494:506 arg1 sequences 517:525 serum-derived HBs gene sequences 494:525 serum-derived HBs gene sequences 494:525 To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. 37112819 7 13 theme insertion 1102:1110 arg1 variant 1112:1118 the hyperglycosylated insertion variant 1080:1118 the hyperglycosylated insertion variant 1080:1118 Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. 37112819 3 14 theme variants 456:463 arg1 presence 412:419 the presence 408:419 the presence of immune and/or diagnostic escape variants 408:463 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 2 15 from Mutations 195:203 arg1 antigen 220:226 the surface antigen 208:226 the surface antigen of HBV (HBsAg) 208:241 Mutations in the surface antigen of HBV (HBsAg) may alter its antigenicity, infectivity, and transmissibility. 37112819 2 15 from Mutations 195:203 arg1 HBsAg 236:240 HBsAg 236:240 HBsAg 236:240 Mutations in the surface antigen of HBV (HBsAg) may alter its antigenicity, infectivity, and transmissibility. 37112819 5 16 from mutations 665:673 arg1 loop 692:695 the antigenic loop 678:695 the antigenic loop of HBsAg 678:704 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 9 17 theme immune 1426:1431 arg1 mutations 1440:1448 immune escape mutations 1426:1448 immune escape mutations 1426:1448 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 5 18 theme variant 763:769 arg1 sequences 771:779 the variant sequences 759:779 the variant sequences 759:779 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 5 18 theme variant 763:769 arg1 insertion 832:840 a previously undescribed six-nucleotide insertion 792:840 a previously undescribed six-nucleotide insertion 792:840 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 9 19 theme critical 1457:1464 arg1 impact 1466:1471 a critical impact 1455:1471 a critical impact 1455:1471 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 8 20 theme natural 1183:1189 arg1 antibodies 1218:1227 natural infection-induced anti-HBs antibodies 1183:1227 natural infection-induced anti-HBs antibodies 1183:1227 Additionally, the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies was severely impaired. 37112819 4 21 theme subgenotype 628:638 arg1 D3 646:647 exclusively non-wildtype HBV subgenotype (sgt) D3 599:647 exclusively non-wildtype HBV subgenotype (sgt) D3 599:647 To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. 37112819 0 22 theme Diagnostic 96:105 arg1 Escape 118:123 Diagnostic and Immune Escape 96:123 Diagnostic and Immune Escape 96:123 A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape. 37112819 3 23 from DNA 333:335 arg1 parallel 375:382 parallel 375:382 parallel with anti-HBs 375:396 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 3 24 theme low-level 356:364 arg1 HBsAg 366:370 detectable but low-level HBsAg 341:370 detectable but low-level HBsAg in parallel with anti-HBs 341:396 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 5 25 located found 750:754 arg1 sequences 771:779 the variant sequences 759:779 the variant sequences 759:779 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 5 25 located found 750:754 arg2 mutations 665:673 Three distinct mutations 650:673 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation 650:743 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 5 25 located found 750:754 arg1 insertion 832:840 a previously undescribed six-nucleotide insertion 792:840 a previously undescribed six-nucleotide insertion 792:840 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 4 26 theme HBV 624:626 arg1 D3 646:647 exclusively non-wildtype HBV subgenotype (sgt) D3 599:647 exclusively non-wildtype HBV subgenotype (sgt) D3 599:647 To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. 37112819 0 27 theme Novel 2:6 arg1 Insertion 8:16 A Novel Insertion 0:16 A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation 0:87 A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape. 37112819 6 28 theme secreted 856:863 arg1 HBsAg 865:869 Cellular and secreted HBsAg 843:869 Cellular and secreted HBsAg 843:869 Cellular and secreted HBsAg was analyzed for N-glycosylation in Western blot after expression in human hepatoma cells. 37112819 9 29 theme six-nucleotide 1302:1315 arg1 insertion 1317:1325 the novel six-nucleotide insertion 1292:1325 the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations 1292:1448 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 7 30 theme diagnostic 1034:1043 arg1 assays 1045:1050 four widely used, state-of-the-art diagnostic assays 999:1050 four widely used, state-of-the-art diagnostic assays 999:1050 Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. 37112819 4 31 theme sgt 641:643 arg1 D3 646:647 exclusively non-wildtype HBV subgenotype (sgt) D3 599:647 exclusively non-wildtype HBV subgenotype (sgt) D3 599:647 To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. 37112819 4 32 theme gene 512:515 arg1 sequences 517:525 serum-derived HBs gene sequences 494:525 serum-derived HBs gene sequences 494:525 To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. 37112819 9 33 contain have 1450:1453 arg2 impact 1466:1471 a critical impact 1455:1471 a critical impact 1455:1471 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 9 33 contain have 1450:1453 arg1 insertion 1317:1325 the novel six-nucleotide insertion 1292:1325 the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations 1292:1448 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 9 33 contain have 1450:1453 arg1 mutations 1369:1377 two other previously described mutations 1338:1377 the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations 1292:1448 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 6 34 theme Cellular 843:850 arg1 HBsAg 865:869 Cellular and secreted HBsAg 843:869 Cellular and secreted HBsAg 843:869 Cellular and secreted HBsAg was analyzed for N-glycosylation in Western blot after expression in human hepatoma cells. 37112819 5 35 theme undescribed 805:815 arg1 insertion 832:840 a previously undescribed six-nucleotide insertion 792:840 a previously undescribed six-nucleotide insertion 792:840 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 4 36 theme HBs 508:510 arg1 sequences 517:525 serum-derived HBs gene sequences 494:525 serum-derived HBs gene sequences 494:525 To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. 37112819 5 37 theme distinct 656:663 arg1 mutations 665:673 Three distinct mutations 650:673 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation 650:743 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 9 38 theme in 1476:1477 arg1 diagnostics 1485:1495 in vitro diagnostics 1476:1495 in vitro diagnostics 1476:1495 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 3 39 theme HBV 329:331 arg1 DNA 333:335 HBV DNA 329:335 HBV DNA 329:335 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 6 40 theme hepatoma 946:953 arg1 cells 955:959 human hepatoma cells 940:959 human hepatoma cells 940:959 Cellular and secreted HBsAg was analyzed for N-glycosylation in Western blot after expression in human hepatoma cells. 37112819 0 41 theme Immune 111:116 arg1 Escape 118:123 Diagnostic and Immune Escape 96:123 Diagnostic and Immune Escape 96:123 A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape. 37112819 9 42 gly hyperglycosylation 1387:1404 arg1 combination 1409:1419 combination 1409:1419 combination with immune escape mutations 1409:1448 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 1 43 theme global 173:178 arg1 infection 158:166 Chronic hepatitis B virus (HBV) infection 126:166 Chronic hepatitis B virus (HBV) infection 126:166 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 1 43 theme global 173:178 arg1 threat 187:192 a global health threat 171:192 a global health threat 171:192 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 0 44 theme Hepatitis 25:33 arg1 Virus 37:41 Hepatitis B Virus 25:41 the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation 21:87 A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape. 37112819 6 45 theme human 940:944 arg1 cells 955:959 human hepatoma cells 940:959 human hepatoma cells 940:959 Cellular and secreted HBsAg was analyzed for N-glycosylation in Western blot after expression in human hepatoma cells. 37112819 4 46 theme non-wildtype 611:622 arg1 D3 646:647 exclusively non-wildtype HBV subgenotype (sgt) D3 599:647 exclusively non-wildtype HBV subgenotype (sgt) D3 599:647 To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. 37112819 9 47 dep in 1476:1477 arg1 vitro 1479:1483 vitro 1479:1483 vitro 1479:1483 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 1 48 theme health 180:185 arg1 infection 158:166 Chronic hepatitis B virus (HBV) infection 126:166 Chronic hepatitis B virus (HBV) infection 126:166 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 1 48 theme health 180:185 arg1 threat 187:192 a global health threat 171:192 a global health threat 171:192 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 8 49 theme anti-HBs 1209:1216 arg1 antibodies 1218:1227 natural infection-induced anti-HBs antibodies 1183:1227 natural infection-induced anti-HBs antibodies 1183:1227 Additionally, the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies was severely impaired. 37112819 8 50 theme infection-induced 1191:1207 arg1 antibodies 1218:1227 natural infection-induced anti-HBs antibodies 1183:1227 natural infection-induced anti-HBs antibodies 1183:1227 Additionally, the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies was severely impaired. 37112819 5 51 theme six-nucleotide 817:830 arg1 insertion 832:840 a previously undescribed six-nucleotide insertion 792:840 a previously undescribed six-nucleotide insertion 792:840 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 5 52 theme HBsAg 700:704 arg1 loop 692:695 the antigenic loop 678:695 the antigenic loop of HBsAg 678:704 Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. 37112819 0 53 theme Virus 37:41 arg1 Protein 51:57 the Hepatitis B Virus Surface Protein 21:57 the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation 21:87 A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape. 37112819 7 54 dep used 1011:1014 arg1 state-of-the-art 1017:1032 state-of-the-art 1017:1032 state-of-the-art 1017:1032 Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. 37112819 8 55 theme HBsAg 1161:1165 arg1 impaired 1242:1249 impaired 1242:1249 impaired 1242:1249 Additionally, the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies was severely impaired. 37112819 8 55 theme HBsAg 1161:1165 arg1 recognition 1139:1149 the recognition 1135:1149 the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies 1135:1227 Additionally, the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies was severely impaired. 37112819 9 56 theme other 1342:1346 arg1 mutations 1369:1377 two other previously described mutations 1338:1377 the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations 1292:1448 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 3 57 theme diagnostic 438:447 arg1 variants 456:463 immune and/or diagnostic escape variants 424:463 immune and/or diagnostic escape variants 424:463 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 0 58 theme B 35:35 arg1 Virus 37:41 Hepatitis B Virus 25:41 the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation 21:87 A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape. 37112819 4 59 theme serum-derived 494:506 arg1 sequences 517:525 serum-derived HBs gene sequences 494:525 serum-derived HBs gene sequences 494:525 To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. 37112819 3 60 with parallel 375:382 arg1 anti-HBs 389:396 anti-HBs 389:396 anti-HBs 389:396 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 3 61 theme escape 449:454 arg1 variants 456:463 immune and/or diagnostic escape variants 424:463 immune and/or diagnostic escape variants 424:463 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 7 62 theme used 1011:1014 arg1 assays 1045:1050 four widely used, state-of-the-art diagnostic assays 999:1050 four widely used, state-of-the-art diagnostic assays 999:1050 Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. 37112819 2 63 theme HBV 231:233 arg1 antigen 220:226 the surface antigen 208:226 the surface antigen of HBV (HBsAg) 208:241 Mutations in the surface antigen of HBV (HBsAg) may alter its antigenicity, infectivity, and transmissibility. 37112819 2 63 theme HBV 231:233 arg1 HBsAg 236:240 HBsAg 236:240 HBsAg 236:240 Mutations in the surface antigen of HBV (HBsAg) may alter its antigenicity, infectivity, and transmissibility. 37112819 3 64 theme immune 424:429 arg1 variants 456:463 immune and/or diagnostic escape variants 424:463 immune and/or diagnostic escape variants 424:463 A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. 37112819 9 65 with combination 1409:1419 arg1 mutations 1440:1448 immune escape mutations 1426:1448 immune escape mutations 1426:1448 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 8 66 theme mutant 1154:1159 arg1 HBsAg 1161:1165 mutant HBsAg 1154:1165 mutant HBsAg 1154:1165 Additionally, the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies was severely impaired. 37112819 6 67 from expression 926:935 arg1 cells 955:959 human hepatoma cells 940:959 human hepatoma cells 940:959 Cellular and secreted HBsAg was analyzed for N-glycosylation in Western blot after expression in human hepatoma cells. 37112819 1 68 theme Chronic 126:132 arg1 infection 158:166 Chronic hepatitis B virus (HBV) infection 126:166 Chronic hepatitis B virus (HBV) infection 126:166 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 1 68 theme Chronic 126:132 arg1 threat 187:192 a global health threat 171:192 a global health threat 171:192 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 4 69 with infection 584:592 arg1 D3 646:647 exclusively non-wildtype HBV subgenotype (sgt) D3 599:647 exclusively non-wildtype HBV subgenotype (sgt) D3 599:647 To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. 37112819 9 70 theme infection 1542:1550 arg1 risk 1521:1524 the risk 1517:1524 the risk of breakthrough infection by evasion of vaccine-induced immunity 1517:1589 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 1 71 theme hepatitis 134:142 arg1 HBV 153:155 HBV 153:155 HBV 153:155 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 1 71 theme hepatitis 134:142 arg1 virus 146:150 hepatitis B virus 134:150 Chronic hepatitis B virus (HBV) infection 126:166 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 9 72 theme described 1359:1367 arg1 mutations 1369:1377 two other previously described mutations 1338:1377 the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations 1292:1448 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 9 73 theme immunity 1582:1589 arg1 evasion 1555:1561 evasion 1555:1561 evasion of vaccine-induced immunity 1555:1589 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37112819 0 74 theme Surface 43:49 arg1 Protein 51:57 the Hepatitis B Virus Surface Protein 21:57 the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation 21:87 A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape. 37112819 6 75 theme Western 907:913 arg1 blot 915:918 Western blot 907:918 Western blot 907:918 Cellular and secreted HBsAg was analyzed for N-glycosylation in Western blot after expression in human hepatoma cells. 37112819 2 76 theme surface 212:218 arg1 antigen 220:226 the surface antigen 208:226 the surface antigen of HBV (HBsAg) 208:241 Mutations in the surface antigen of HBV (HBsAg) may alter its antigenicity, infectivity, and transmissibility. 37112819 2 76 theme surface 212:218 arg1 HBsAg 236:240 HBsAg 236:240 HBsAg 236:240 Mutations in the surface antigen of HBV (HBsAg) may alter its antigenicity, infectivity, and transmissibility. 37112819 7 77 theme Secreted 962:969 arg1 HBsAg 971:975 Secreted HBsAg 962:975 Secreted HBsAg 962:975 Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. 37112819 1 78 theme B 144:144 arg1 HBV 153:155 HBV 153:155 HBV 153:155 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 1 78 theme B 144:144 arg1 virus 146:150 hepatitis B virus 134:150 Chronic hepatitis B virus (HBV) infection 126:166 Chronic hepatitis B virus (HBV) infection is a global health threat. 37112819 9 79 theme escape 1433:1438 arg1 mutations 1440:1448 immune escape mutations 1426:1448 immune escape mutations 1426:1448 Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. 37196774 0 0 theme gastric 84:90 arg1 progression 99:109 gastric cancer progression 84:109 gastric cancer progression 84:109 O-GlcNAcylation enhances Reticulon 2 protein stability and its promotive effects on gastric cancer progression. 37196774 5 1 theme O-GlcNAc 687:694 arg1 transferase 696:706 O-GlcNAc transferase 687:706 O-GlcNAc transferase (OGT) 687:712 We found that RTN2 interacted with O-GlcNAc transferase (OGT) and was modified by O-GlcNAc. 37196774 5 1 theme O-GlcNAc 687:694 arg1 OGT 709:711 OGT 709:711 OGT 709:711 We found that RTN2 interacted with O-GlcNAc transferase (OGT) and was modified by O-GlcNAc. 37196774 8 2 theme cellular 1027:1034 arg1 proliferation 1036:1048 cellular proliferation 1027:1048 cellular proliferation 1027:1048 Consistently, the stimulative effects of RTN2 on cellular proliferation and migration were abrogated by OGT inhibition. 37196774 12 3 theme cancer 1647:1652 arg1 therapies 1654:1662 gastric cancer therapies 1639:1662 gastric cancer therapies 1639:1662 Targeting RTN2 O-GlcNAcylation might provide new ideas for gastric cancer therapies. 37196774 9 4 theme ERK 1299:1301 arg1 level 1290:1294 the phosphorylation level 1270:1294 the level of total O-GlcNAcylation as well as the phosphorylation level of ERK 1224:1301 Tissue microarray with immumohistochemical staining also confirmed that the expression of RTN2 was positively correlated with the level of total O-GlcNAcylation as well as the phosphorylation level of ERK. 37196774 9 4 theme ERK 1299:1301 arg1 level 1228:1232 the level 1224:1232 the level of total O-GlcNAcylation as well as the phosphorylation level of ERK 1224:1301 Tissue microarray with immumohistochemical staining also confirmed that the expression of RTN2 was positively correlated with the level of total O-GlcNAcylation as well as the phosphorylation level of ERK. 37196774 7 5 theme signalling 933:942 arg1 activation 915:924 RTN2-induced activation 902:924 RTN2-induced activation of ERK signalling 902:942 Furthermore, our results demonstrated that RTN2-induced activation of ERK signalling was dependent on O-GlcNAcylation. 37196774 2 6 link O-linked 240:247 arg1 β-N-acetylglucosaminylation 249:275 Protein O-linked β-N-acetylglucosaminylation 232:275 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 232:293 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 2 6 link O-linked 240:247 arg1 feature 308:314 a general feature 298:314 a general feature 298:314 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 2 6 link O-linked 240:247 arg1 O-GlcNAcylation 278:292 O-GlcNAcylation 278:292 O-GlcNAcylation 278:292 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 9 7 theme phosphorylation 1274:1288 arg1 level 1290:1294 the phosphorylation level 1270:1294 the level of total O-GlcNAcylation as well as the phosphorylation level of ERK 1224:1301 Tissue microarray with immumohistochemical staining also confirmed that the expression of RTN2 was positively correlated with the level of total O-GlcNAcylation as well as the phosphorylation level of ERK. 37196774 2 8 theme general 300:306 arg1 β-N-acetylglucosaminylation 249:275 Protein O-linked β-N-acetylglucosaminylation 232:275 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 232:293 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 2 8 theme general 300:306 arg1 feature 308:314 a general feature 298:314 a general feature 298:314 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 10 9 theme staining 1340:1347 arg1 intensity 1349:1357 combined RTN2 and O-GlcNAc staining intensity 1313:1357 combined RTN2 and O-GlcNAc staining intensity 1313:1357 Besides, combined RTN2 and O-GlcNAc staining intensity could improve predictive accuracy for gastric cancer patients' survival compared with each alone. 37196774 4 10 theme gastric 636:642 arg1 cancer 644:649 gastric cancer 636:649 gastric cancer 636:649 In this study, we explored the influence of O-GlcNAcylation on RTN2 expression and its promotive role in gastric cancer. 37196774 0 11 theme cancer 92:97 arg1 progression 99:109 gastric cancer progression 84:109 gastric cancer progression 84:109 O-GlcNAcylation enhances Reticulon 2 protein stability and its promotive effects on gastric cancer progression. 37196774 10 12 theme gastric 1397:1403 arg1 patients 1412:1419 gastric cancer patients 1397:1419 gastric cancer patients' survival 1397:1429 Besides, combined RTN2 and O-GlcNAc staining intensity could improve predictive accuracy for gastric cancer patients' survival compared with each alone. 37196774 10 13 theme predictive 1373:1382 arg1 accuracy 1384:1391 predictive accuracy 1373:1391 predictive accuracy for gastric cancer patients' survival 1373:1429 Besides, combined RTN2 and O-GlcNAc staining intensity could improve predictive accuracy for gastric cancer patients' survival compared with each alone. 37196774 4 14 from role 628:631 arg1 cancer 644:649 gastric cancer 636:649 gastric cancer 636:649 In this study, we explored the influence of O-GlcNAcylation on RTN2 expression and its promotive role in gastric cancer. 37196774 11 15 theme oncogenic 1541:1549 arg1 functions 1551:1559 its oncogenic functions 1537:1559 its oncogenic functions in gastric cancer 1537:1577 Altogether, these findings suggest that O-GlcNAcylation on RTN2 was pivotal for its oncogenic functions in gastric cancer. 37196774 7 16 theme ERK 929:931 arg1 signalling 933:942 ERK signalling 929:942 ERK signalling 929:942 Furthermore, our results demonstrated that RTN2-induced activation of ERK signalling was dependent on O-GlcNAcylation. 37196774 0 17 from stability 45:53 arg1 progression 99:109 gastric cancer progression 84:109 gastric cancer progression 84:109 O-GlcNAcylation enhances Reticulon 2 protein stability and its promotive effects on gastric cancer progression. 37196774 6 18 theme cancer 845:850 arg1 cells 852:856 gastric cancer cells 837:856 gastric cancer cells 837:856 O-GlcNAcylation enhanced RTN2 protein stability via attenuating its lysosomal degradation in gastric cancer cells. 37196774 11 19 from functions 1551:1559 arg1 cancer 1572:1577 gastric cancer 1564:1577 gastric cancer 1564:1577 Altogether, these findings suggest that O-GlcNAcylation on RTN2 was pivotal for its oncogenic functions in gastric cancer. 37196774 7 20 theme RTN2-induced 902:913 arg1 activation 915:924 RTN2-induced activation 902:924 RTN2-induced activation of ERK signalling 902:942 Furthermore, our results demonstrated that RTN2-induced activation of ERK signalling was dependent on O-GlcNAcylation. 37196774 8 21 from effects 1008:1014 arg1 migration 1054:1062 migration 1054:1062 migration 1054:1062 Consistently, the stimulative effects of RTN2 on cellular proliferation and migration were abrogated by OGT inhibition. 37196774 8 21 from effects 1008:1014 arg1 proliferation 1036:1048 cellular proliferation 1027:1048 cellular proliferation 1027:1048 Consistently, the stimulative effects of RTN2 on cellular proliferation and migration were abrogated by OGT inhibition. 37196774 9 22 with microarray 1105:1114 arg1 staining 1141:1148 immumohistochemical staining 1121:1148 immumohistochemical staining 1121:1148 Tissue microarray with immumohistochemical staining also confirmed that the expression of RTN2 was positively correlated with the level of total O-GlcNAcylation as well as the phosphorylation level of ERK. 37196774 6 23 theme gastric 837:843 arg1 cells 852:856 gastric cancer cells 837:856 gastric cancer cells 837:856 O-GlcNAcylation enhanced RTN2 protein stability via attenuating its lysosomal degradation in gastric cancer cells. 37196774 9 24 theme RTN2 1188:1191 arg1 expression 1174:1183 the expression 1170:1183 the expression of RTN2 1170:1191 Tissue microarray with immumohistochemical staining also confirmed that the expression of RTN2 was positively correlated with the level of total O-GlcNAcylation as well as the phosphorylation level of ERK. 37196774 4 25 from expression 599:608 arg1 cancer 644:649 gastric cancer 636:649 gastric cancer 636:649 In this study, we explored the influence of O-GlcNAcylation on RTN2 expression and its promotive role in gastric cancer. 37196774 4 26 theme RTN2 594:597 arg1 expression 599:608 RTN2 expression 594:608 RTN2 expression 594:608 In this study, we explored the influence of O-GlcNAcylation on RTN2 expression and its promotive role in gastric cancer. 37196774 0 27 theme Reticulon 25:33 arg1 stability 45:53 Reticulon 2 protein stability 25:53 Reticulon 2 protein stability 25:53 O-GlcNAcylation enhances Reticulon 2 protein stability and its promotive effects on gastric cancer progression. 37196774 12 28 theme gastric 1639:1645 arg1 therapies 1654:1662 gastric cancer therapies 1639:1662 gastric cancer therapies 1639:1662 Targeting RTN2 O-GlcNAcylation might provide new ideas for gastric cancer therapies. 37196774 12 29 theme new 1625:1627 arg1 ideas 1629:1633 new ideas 1625:1633 new ideas for gastric cancer therapies 1625:1662 Targeting RTN2 O-GlcNAcylation might provide new ideas for gastric cancer therapies. 37196774 10 30 theme cancer 1405:1410 arg1 patients 1412:1419 gastric cancer patients 1397:1419 gastric cancer patients' survival 1397:1429 Besides, combined RTN2 and O-GlcNAc staining intensity could improve predictive accuracy for gastric cancer patients' survival compared with each alone. 37196774 6 31 from degradation 822:832 arg1 cells 852:856 gastric cancer cells 837:856 gastric cancer cells 837:856 O-GlcNAcylation enhanced RTN2 protein stability via attenuating its lysosomal degradation in gastric cancer cells. 37196774 11 32 theme gastric 1564:1570 arg1 cancer 1572:1577 gastric cancer 1564:1577 gastric cancer 1564:1577 Altogether, these findings suggest that O-GlcNAcylation on RTN2 was pivotal for its oncogenic functions in gastric cancer. 37196774 2 33 theme Protein 232:238 arg1 β-N-acetylglucosaminylation 249:275 Protein O-linked β-N-acetylglucosaminylation 232:275 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 232:293 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 2 33 theme Protein 232:238 arg1 feature 308:314 a general feature 298:314 a general feature 298:314 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 2 33 theme Protein 232:238 arg1 O-GlcNAcylation 278:292 O-GlcNAcylation 278:292 O-GlcNAcylation 278:292 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 8 34 theme RTN2 1019:1022 arg1 effects 1008:1014 the stimulative effects 992:1014 the stimulative effects of RTN2 on cellular proliferation and migration 992:1062 Consistently, the stimulative effects of RTN2 on cellular proliferation and migration were abrogated by OGT inhibition. 37196774 0 35 theme protein 37:43 arg1 stability 45:53 Reticulon 2 protein stability 25:53 Reticulon 2 protein stability 25:53 O-GlcNAcylation enhances Reticulon 2 protein stability and its promotive effects on gastric cancer progression. 37196774 4 36 theme promotive 618:626 arg1 role 628:631 its promotive role 614:631 its promotive role in gastric cancer 614:649 In this study, we explored the influence of O-GlcNAcylation on RTN2 expression and its promotive role in gastric cancer. 37196774 0 37 from effects 73:79 arg1 progression 99:109 gastric cancer progression 84:109 gastric cancer progression 84:109 O-GlcNAcylation enhances Reticulon 2 protein stability and its promotive effects on gastric cancer progression. 37196774 10 38 theme O-GlcNAc 1331:1338 arg1 intensity 1349:1357 combined RTN2 and O-GlcNAc staining intensity 1313:1357 combined RTN2 and O-GlcNAc staining intensity 1313:1357 Besides, combined RTN2 and O-GlcNAc staining intensity could improve predictive accuracy for gastric cancer patients' survival compared with each alone. 37196774 6 39 theme lysosomal 812:820 arg1 degradation 822:832 its lysosomal degradation 808:832 its lysosomal degradation in gastric cancer cells 808:856 O-GlcNAcylation enhanced RTN2 protein stability via attenuating its lysosomal degradation in gastric cancer cells. 37196774 5 40 mod modified 722:729 arg1 RTN2 666:669 RTN2 666:669 RTN2 666:669 We found that RTN2 interacted with O-GlcNAc transferase (OGT) and was modified by O-GlcNAc. 37196774 5 40 mod modified 722:729 arg3 O-GlcNAc 734:741 O-GlcNAc 734:741 O-GlcNAc 734:741 We found that RTN2 interacted with O-GlcNAc transferase (OGT) and was modified by O-GlcNAc. 37196774 2 41 from modification 410:421 arg1 serine/threonine 426:441 serine/threonine 426:441 serine/threonine 426:441 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 1 42 theme previous 116:123 arg1 study 125:129 Our previous study 112:129 Our previous study 112:129 Our previous study indicated that Reticulon 2 (RTN2) was upregulated and facilitated the progression of gastric cancer. 37196774 4 43 from influence 562:570 arg1 expression 599:608 RTN2 expression 594:608 RTN2 expression 594:608 In this study, we explored the influence of O-GlcNAcylation on RTN2 expression and its promotive role in gastric cancer. 37196774 4 43 from influence 562:570 arg1 role 628:631 its promotive role 614:631 its promotive role in gastric cancer 614:649 In this study, we explored the influence of O-GlcNAcylation on RTN2 expression and its promotive role in gastric cancer. 37196774 12 44 theme RTN2 1590:1593 arg1 O-GlcNAcylation 1595:1609 RTN2 O-GlcNAcylation 1590:1609 RTN2 O-GlcNAcylation 1590:1609 Targeting RTN2 O-GlcNAcylation might provide new ideas for gastric cancer therapies. 37196774 2 45 theme protein 352:358 arg1 activity 360:367 protein activity 352:367 protein activity 352:367 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 9 46 theme Tissue 1098:1103 arg1 microarray 1105:1114 Tissue microarray 1098:1114 Tissue microarray with immumohistochemical staining 1098:1148 Tissue microarray with immumohistochemical staining also confirmed that the expression of RTN2 was positively correlated with the level of total O-GlcNAcylation as well as the phosphorylation level of ERK. 37196774 4 47 theme O-GlcNAcylation 575:589 arg1 influence 562:570 the influence 558:570 the influence of O-GlcNAcylation on RTN2 expression and its promotive role in gastric cancer 558:649 In this study, we explored the influence of O-GlcNAcylation on RTN2 expression and its promotive role in gastric cancer. 37196774 8 48 theme OGT 1082:1084 arg1 inhibition 1086:1095 OGT inhibition 1082:1095 OGT inhibition 1082:1095 Consistently, the stimulative effects of RTN2 on cellular proliferation and migration were abrogated by OGT inhibition. 37196774 9 49 theme total 1237:1241 arg1 O-GlcNAcylation 1243:1257 total O-GlcNAcylation 1237:1257 total O-GlcNAcylation 1237:1257 Tissue microarray with immumohistochemical staining also confirmed that the expression of RTN2 was positively correlated with the level of total O-GlcNAcylation as well as the phosphorylation level of ERK. 37196774 1 50 theme gastric 216:222 arg1 cancer 224:229 gastric cancer 216:229 gastric cancer 216:229 Our previous study indicated that Reticulon 2 (RTN2) was upregulated and facilitated the progression of gastric cancer. 37196774 8 51 theme stimulative 996:1006 arg1 effects 1008:1014 the stimulative effects 992:1014 the stimulative effects of RTN2 on cellular proliferation and migration 992:1062 Consistently, the stimulative effects of RTN2 on cellular proliferation and migration were abrogated by OGT inhibition. 37196774 9 52 theme O-GlcNAcylation 1243:1257 arg1 level 1290:1294 the phosphorylation level 1270:1294 the level of total O-GlcNAcylation as well as the phosphorylation level of ERK 1224:1301 Tissue microarray with immumohistochemical staining also confirmed that the expression of RTN2 was positively correlated with the level of total O-GlcNAcylation as well as the phosphorylation level of ERK. 37196774 9 52 theme O-GlcNAcylation 1243:1257 arg1 level 1228:1232 the level 1224:1232 the level of total O-GlcNAcylation as well as the phosphorylation level of ERK 1224:1301 Tissue microarray with immumohistochemical staining also confirmed that the expression of RTN2 was positively correlated with the level of total O-GlcNAcylation as well as the phosphorylation level of ERK. 37196774 10 53 theme RTN2 1322:1325 arg1 intensity 1349:1357 combined RTN2 and O-GlcNAc staining intensity 1313:1357 combined RTN2 and O-GlcNAc staining intensity 1313:1357 Besides, combined RTN2 and O-GlcNAc staining intensity could improve predictive accuracy for gastric cancer patients' survival compared with each alone. 37196774 1 54 theme cancer 224:229 arg1 progression 201:211 the progression 197:211 the progression of gastric cancer 197:229 Our previous study indicated that Reticulon 2 (RTN2) was upregulated and facilitated the progression of gastric cancer. 37196774 11 55 from O-GlcNAcylation 1497:1511 arg1 RTN2 1516:1519 RTN2 1516:1519 RTN2 1516:1519 Altogether, these findings suggest that O-GlcNAcylation on RTN2 was pivotal for its oncogenic functions in gastric cancer. 37196774 6 56 theme protein 774:780 arg1 stability 782:790 RTN2 protein stability 769:790 RTN2 protein stability 769:790 O-GlcNAcylation enhanced RTN2 protein stability via attenuating its lysosomal degradation in gastric cancer cells. 37196774 2 57 theme post-translational 391:408 arg1 modification 410:421 post-translational modification 391:421 post-translational modification on serine/threonine 391:441 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 9 58 theme immumohistochemical 1121:1139 arg1 staining 1141:1148 immumohistochemical staining 1121:1148 immumohistochemical staining 1121:1148 Tissue microarray with immumohistochemical staining also confirmed that the expression of RTN2 was positively correlated with the level of total O-GlcNAcylation as well as the phosphorylation level of ERK. 37196774 0 59 theme promotive 63:71 arg1 effects 73:79 its promotive effects 59:79 its promotive effects on gastric cancer progression 59:109 O-GlcNAcylation enhances Reticulon 2 protein stability and its promotive effects on gastric cancer progression. 37196774 2 60 theme O-linked 240:247 arg1 β-N-acetylglucosaminylation 249:275 Protein O-linked β-N-acetylglucosaminylation 232:275 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 232:293 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 2 60 theme O-linked 240:247 arg1 feature 308:314 a general feature 298:314 a general feature 298:314 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 2 60 theme O-linked 240:247 arg1 O-GlcNAcylation 278:292 O-GlcNAcylation 278:292 O-GlcNAcylation 278:292 Protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a general feature during tumorigenesis, and regulates protein activity and stability through post-translational modification on serine/threonine. 37196774 6 61 theme RTN2 769:772 arg1 stability 782:790 RTN2 protein stability 769:790 RTN2 protein stability 769:790 O-GlcNAcylation enhanced RTN2 protein stability via attenuating its lysosomal degradation in gastric cancer cells. 37196774 10 62 theme combined 1313:1320 arg1 intensity 1349:1357 combined RTN2 and O-GlcNAc staining intensity 1313:1357 combined RTN2 and O-GlcNAc staining intensity 1313:1357 Besides, combined RTN2 and O-GlcNAc staining intensity could improve predictive accuracy for gastric cancer patients' survival compared with each alone. 37033243 8 0 theme GSK-3β 1546:1551 arg1 O-GlcNAcylation 1527:1541 O-GlcNAcylation 1527:1541 O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy 1527:1672 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 6 1 from Ser9 1002:1005 arg1 O-GlcNAcylation 973:987 O-GlcNAcylation 973:987 O-GlcNAcylation of GSK-3β at Ser9 973:1005 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 3 2 theme constriction 566:577 arg1 surgery 585:591 transverse aortic constriction (TAC) surgery 548:591 transverse aortic constriction (TAC) surgery 548:591 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 6 3 theme T 1195:1195 arg1 cell 1197:1200 nuclear factor of activated T cell 1167:1200 nuclear factor of activated T cell (NFAT) activity 1167:1216 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 6 3 theme T 1195:1195 arg1 NFAT 1203:1206 NFAT 1203:1206 NFAT 1203:1206 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 8 4 theme NFAT 1629:1632 arg1 activity 1634:1641 NFAT activity 1629:1641 NFAT activity 1629:1641 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 7 5 theme inhibitor 1351:1359 arg1 treatment 1329:1337 the treatment 1325:1337 the treatment of a GSK-3β inhibitor, TDZD-8 1325:1367 Finally, the thinned LV wall and reduced cardiac function induced by TAC4W in Ogt-Tg mice was reversed by the treatment of a GSK-3β inhibitor, TDZD-8. 37033243 6 6 theme Ogt-Tg 1095:1100 arg1 mice 1102:1105 Ogt-Tg mice 1095:1105 Ogt-Tg mice 1095:1105 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 6 7 theme of 1182:1183 arg1 cell 1197:1200 nuclear factor of activated T cell 1167:1200 nuclear factor of activated T cell (NFAT) activity 1167:1216 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 6 7 theme of 1182:1183 arg1 NFAT 1203:1206 NFAT 1203:1206 NFAT 1203:1206 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 5 8 theme left 844:847 arg1 LV 860:861 LV 860:861 LV 860:861 The myocardium of left ventricle (LV) in Ogt-Tg mice became much thinner than that in WT mice. 37033243 5 8 theme left 844:847 arg1 ventricle 849:857 left ventricle 844:857 left ventricle (LV) 844:862 The myocardium of left ventricle (LV) in Ogt-Tg mice became much thinner than that in WT mice. 37033243 6 9 theme nuclear 1167:1173 arg1 cell 1197:1200 nuclear factor of activated T cell 1167:1200 nuclear factor of activated T cell (NFAT) activity 1167:1216 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 6 9 theme nuclear 1167:1173 arg1 NFAT 1203:1206 NFAT 1203:1206 NFAT 1203:1206 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 8 10 theme cardiac 1654:1660 arg1 hypertrophy 1662:1672 cardiac hypertrophy 1654:1672 cardiac hypertrophy 1654:1672 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 3 11 theme wild 610:613 arg1 WT 621:622 WT 621:622 WT 621:622 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 3 11 theme wild 610:613 arg1 type 615:618 wild type 610:618 wild type (WT) 610:623 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 3 12 theme Ogt 629:631 arg1 mice 653:656 Ogt transgenic (Ogt-Tg) mice 629:656 Ogt transgenic (Ogt-Tg) mice 629:656 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 1 13 theme O-linked 243:250 arg1 O-GlcNAc 275:282 O-GlcNAc 275:282 O-GlcNAc 275:282 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 1 13 theme O-linked 243:250 arg1 β-N-acetylglucosamine 252:272 O-linked β-N-acetylglucosamine 243:272 O-linked β-N-acetylglucosamine (O-GlcNAc) 243:283 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 6 14 theme subsequent 1140:1149 arg1 inactivation 1151:1162 subsequent inactivation 1140:1162 subsequent inactivation 1140:1162 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 1 15 theme O-GlcNAc 149:156 arg1 transferase 158:168 O-GlcNAc transferase 149:168 O-GlcNAc transferase (OGT) 149:174 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 1 15 theme O-GlcNAc 149:156 arg1 OGT 171:173 OGT 171:173 OGT 171:173 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 7 16 theme reduced 1252:1258 arg1 function 1268:1275 reduced cardiac function 1252:1275 reduced cardiac function 1252:1275 Finally, the thinned LV wall and reduced cardiac function induced by TAC4W in Ogt-Tg mice was reversed by the treatment of a GSK-3β inhibitor, TDZD-8. 37033243 4 17 theme mice 718:721 arg1 lower 741:745 lower 741:745 lower 741:745 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 4 17 theme mice 718:721 arg1 function 699:706 the heart function 689:706 the heart function of Ogt-Tg mice 689:721 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 6 18 theme WT 964:965 arg1 mice 967:970 WT mice 964:970 WT mice 964:970 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 4 19 theme heart 693:697 arg1 lower 741:745 lower 741:745 lower 741:745 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 4 19 theme heart 693:697 arg1 function 699:706 the heart function 689:706 the heart function of Ogt-Tg mice 689:721 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 3 20 from effect 443:448 arg1 hypertrophy 506:516 pressure overload-induced cardiac hypertrophy 472:516 pressure overload-induced cardiac hypertrophy 472:516 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 3 20 from effect 443:448 arg1 failure 539:545 subsequent heart failure 522:545 subsequent heart failure 522:545 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 1 21 theme many 186:189 arg1 functions 191:199 many functions 186:199 many functions of proteins 186:211 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 0 22 theme cardiac 120:126 arg1 hypertrophy 128:138 compensatory cardiac hypertrophy 107:138 compensatory cardiac hypertrophy in mice 107:146 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 9 23 theme therapeutic 1706:1716 arg1 strategy 1718:1725 a new therapeutic strategy 1700:1725 a new therapeutic strategy for cardiac hypertrophy and subsequent heart failure 1700:1778 Our findings may provide a new therapeutic strategy for cardiac hypertrophy and subsequent heart failure. 37033243 3 24 theme pressure 472:479 arg1 hypertrophy 506:516 pressure overload-induced cardiac hypertrophy 472:516 pressure overload-induced cardiac hypertrophy 472:516 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 7 25 theme LV 1240:1241 arg1 wall 1243:1246 the thinned LV wall 1228:1246 the thinned LV wall 1228:1246 Finally, the thinned LV wall and reduced cardiac function induced by TAC4W in Ogt-Tg mice was reversed by the treatment of a GSK-3β inhibitor, TDZD-8. 37033243 8 26 theme pressure 1433:1440 arg1 failure 1465:1471 pressure overload-induced heart failure 1433:1471 pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy 1433:1521 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 3 27 theme O-GlcNAcylation 453:467 arg1 effect 443:448 the effect 439:448 the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure 439:545 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 0 28 theme O-GlcNAcylation-induced 0:22 arg1 activation 31:40 O-GlcNAcylation-induced GSK-3β activation 0:40 O-GlcNAcylation-induced GSK-3β activation 0:40 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 8 29 theme heart 1459:1463 arg1 failure 1465:1471 pressure overload-induced heart failure 1433:1471 pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy 1433:1521 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 5 30 theme WT 912:913 arg1 mice 915:918 WT mice 912:918 WT mice 912:918 The myocardium of left ventricle (LV) in Ogt-Tg mice became much thinner than that in WT mice. 37033243 9 31 theme subsequent 1755:1764 arg1 failure 1772:1778 subsequent heart failure 1755:1778 subsequent heart failure 1755:1778 Our findings may provide a new therapeutic strategy for cardiac hypertrophy and subsequent heart failure. 37033243 8 32 theme due 1473:1475 arg1 failure 1465:1471 pressure overload-induced heart failure 1433:1471 pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy 1433:1521 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 4 33 theme increased 803:811 arg1 levels 817:822 increased ANP levels 803:822 increased ANP levels 803:822 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 3 34 theme cardiac 498:504 arg1 hypertrophy 506:516 pressure overload-induced cardiac hypertrophy 472:516 pressure overload-induced cardiac hypertrophy 472:516 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 0 35 theme pressure 55:62 arg1 failure 87:93 pressure overload-induced heart failure 55:93 pressure overload-induced heart failure 55:93 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 0 36 theme heart 81:85 arg1 failure 87:93 pressure overload-induced heart failure 55:93 pressure overload-induced heart failure 55:93 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 4 37 theme reduced 769:775 arg1 shortening 788:797 reduced fractional shortening 769:797 reduced fractional shortening 769:797 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 3 38 theme heart 533:537 arg1 failure 539:545 subsequent heart failure 522:545 subsequent heart failure 522:545 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 8 39 theme cardiac 1503:1509 arg1 hypertrophy 1511:1521 compensatory cardiac hypertrophy 1490:1521 compensatory cardiac hypertrophy 1490:1521 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 8 40 theme phosphorylation 1573:1587 arg1 GSK-3β 1597:1602 GSK-3β 1597:1602 GSK-3β 1597:1602 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 8 40 theme phosphorylation 1573:1587 arg1 site 1589:1592 the phosphorylation site 1569:1592 the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy 1569:1672 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 3 41 theme aortic 559:564 arg1 constriction 566:577 transverse aortic constriction 548:577 transverse aortic constriction (TAC) surgery 548:591 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 3 41 theme aortic 559:564 arg1 TAC 580:582 TAC 580:582 TAC 580:582 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 6 42 theme cell 1197:1200 arg1 activity 1209:1216 nuclear factor of activated T cell (NFAT) activity 1167:1216 nuclear factor of activated T cell (NFAT) activity 1167:1216 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 1 43 theme serine/threonine 292:307 arg1 proteins 321:328 proteins 321:328 proteins 321:328 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 1 43 theme serine/threonine 292:307 arg1 residues 309:316 the serine/threonine residues 288:316 the serine/threonine residues of proteins 288:328 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 7 44 theme GSK-3β 1344:1349 arg1 TDZD-8 1362:1367 TDZD-8 1362:1367 TDZD-8 1362:1367 Finally, the thinned LV wall and reduced cardiac function induced by TAC4W in Ogt-Tg mice was reversed by the treatment of a GSK-3β inhibitor, TDZD-8. 37033243 7 44 theme GSK-3β 1344:1349 arg1 inhibitor 1351:1359 a GSK-3β inhibitor 1342:1359 a GSK-3β inhibitor 1342:1359 Finally, the thinned LV wall and reduced cardiac function induced by TAC4W in Ogt-Tg mice was reversed by the treatment of a GSK-3β inhibitor, TDZD-8. 37033243 6 45 theme mice 1102:1105 arg1 tissues 1084:1090 the heart tissues 1074:1090 the heart tissues of Ogt-Tg mice 1074:1105 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 6 46 theme activated 1185:1193 arg1 cell 1197:1200 nuclear factor of activated T cell 1167:1200 nuclear factor of activated T cell (NFAT) activity 1167:1216 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 6 46 theme activated 1185:1193 arg1 NFAT 1203:1206 NFAT 1203:1206 NFAT 1203:1206 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 5 47 theme ventricle 849:857 arg1 myocardium 830:839 The myocardium 826:839 The myocardium of left ventricle (LV) in Ogt-Tg mice 826:877 The myocardium of left ventricle (LV) in Ogt-Tg mice became much thinner than that in WT mice. 37033243 6 48 theme factor 1175:1180 arg1 cell 1197:1200 nuclear factor of activated T cell 1167:1200 nuclear factor of activated T cell (NFAT) activity 1167:1216 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 6 48 theme factor 1175:1180 arg1 NFAT 1203:1206 NFAT 1203:1206 NFAT 1203:1206 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 1 49 theme proteins 204:211 arg1 functions 191:199 many functions 186:199 many functions of proteins 186:211 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 6 50 theme heart 1078:1082 arg1 tissues 1084:1090 the heart tissues 1074:1090 the heart tissues of Ogt-Tg mice 1074:1105 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 5 51 theme Ogt-Tg 867:872 arg1 mice 874:877 Ogt-Tg mice 867:877 Ogt-Tg mice 867:877 The myocardium of left ventricle (LV) in Ogt-Tg mice became much thinner than that in WT mice. 37033243 3 52 theme transverse 548:557 arg1 constriction 566:577 transverse aortic constriction 548:577 transverse aortic constriction (TAC) surgery 548:591 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 3 52 theme transverse 548:557 arg1 TAC 580:582 TAC 580:582 TAC 580:582 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 0 53 from lack 99:102 arg1 mice 143:146 mice 143:146 mice 143:146 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 5 54 from myocardium 830:839 arg1 mice 874:877 Ogt-Tg mice 867:877 Ogt-Tg mice 867:877 The myocardium of left ventricle (LV) in Ogt-Tg mice became much thinner than that in WT mice. 37033243 0 55 from mice 143:146 arg1 lack 99:102 lack 99:102 lack of compensatory cardiac hypertrophy in mice 99:146 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 7 56 theme Ogt-Tg 1297:1302 arg1 mice 1304:1307 Ogt-Tg mice 1297:1307 Ogt-Tg mice 1297:1307 Finally, the thinned LV wall and reduced cardiac function induced by TAC4W in Ogt-Tg mice was reversed by the treatment of a GSK-3β inhibitor, TDZD-8. 37033243 6 57 theme activity 1209:1216 arg1 activation 1125:1134 its activation 1121:1134 its activation 1121:1134 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 6 57 theme activity 1209:1216 arg1 inactivation 1151:1162 subsequent inactivation 1140:1162 subsequent inactivation 1140:1162 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 3 58 theme Ogt-Tg 645:650 arg1 mice 653:656 Ogt transgenic (Ogt-Tg) mice 629:656 Ogt transgenic (Ogt-Tg) mice 629:656 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 6 59 theme mice 967:970 arg1 tissues 953:959 the heart tissues 943:959 the heart tissues of WT mice 943:970 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 0 60 from hypertrophy 128:138 arg1 mice 143:146 mice 143:146 mice 143:146 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 7 61 theme cardiac 1260:1266 arg1 function 1268:1275 reduced cardiac function 1252:1275 reduced cardiac function 1252:1275 Finally, the thinned LV wall and reduced cardiac function induced by TAC4W in Ogt-Tg mice was reversed by the treatment of a GSK-3β inhibitor, TDZD-8. 37033243 4 62 theme Ogt-Tg 711:716 arg1 mice 718:721 Ogt-Tg mice 711:721 Ogt-Tg mice 711:721 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 3 63 theme transgenic 633:642 arg1 mice 653:656 Ogt transgenic (Ogt-Tg) mice 629:656 Ogt transgenic (Ogt-Tg) mice 629:656 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 4 64 dep mice 763:766 arg1 shortening 788:797 reduced fractional shortening 769:797 reduced fractional shortening 769:797 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 4 64 dep mice 763:766 arg1 levels 817:822 increased ANP levels 803:822 increased ANP levels 803:822 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 0 65 theme compensatory 107:118 arg1 hypertrophy 128:138 compensatory cardiac hypertrophy 107:138 compensatory cardiac hypertrophy in mice 107:146 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 6 66 theme heart 947:951 arg1 tissues 953:959 the heart tissues 943:959 the heart tissues of WT mice 943:970 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 8 67 theme augmented 1395:1403 arg1 O-GlcNAcylation 1405:1419 augmented O-GlcNAcylation 1395:1419 augmented O-GlcNAcylation 1395:1419 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 1 68 link O-linked 243:250 arg1 O-GlcNAc 275:282 O-GlcNAc 275:282 O-GlcNAc 275:282 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 1 68 link O-linked 243:250 arg1 β-N-acetylglucosamine 252:272 O-linked β-N-acetylglucosamine 243:272 O-linked β-N-acetylglucosamine (O-GlcNAc) 243:283 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 0 69 theme hypertrophy 128:138 arg1 lack 99:102 lack 99:102 lack of compensatory cardiac hypertrophy in mice 99:146 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 2 70 from role 344:347 arg1 function 394:401 function 394:401 function 394:401 However, the role of O-GlcNAcylation in cardiac remodeling and function is not fully understood. 37033243 2 70 from role 344:347 arg1 remodeling 379:388 cardiac remodeling 371:388 cardiac remodeling 371:388 However, the role of O-GlcNAcylation in cardiac remodeling and function is not fully understood. 37033243 9 71 theme new 1702:1704 arg1 strategy 1718:1725 a new therapeutic strategy 1700:1725 a new therapeutic strategy for cardiac hypertrophy and subsequent heart failure 1700:1778 Our findings may provide a new therapeutic strategy for cardiac hypertrophy and subsequent heart failure. 37033243 7 72 theme thinned 1232:1238 arg1 wall 1243:1246 the thinned LV wall 1228:1246 the thinned LV wall 1228:1246 Finally, the thinned LV wall and reduced cardiac function induced by TAC4W in Ogt-Tg mice was reversed by the treatment of a GSK-3β inhibitor, TDZD-8. 37033243 8 73 theme overload-induced 1442:1457 arg1 failure 1465:1471 pressure overload-induced heart failure 1433:1471 pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy 1433:1521 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 4 74 theme WT 760:761 arg1 mice 763:766 WT mice 760:766 WT mice (reduced fractional shortening and increased ANP levels) 760:823 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 3 75 theme overload-induced 481:496 arg1 hypertrophy 506:516 pressure overload-induced cardiac hypertrophy 472:516 pressure overload-induced cardiac hypertrophy 472:516 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 0 76 theme GSK-3β 24:29 arg1 activation 31:40 O-GlcNAcylation-induced GSK-3β activation 0:40 O-GlcNAcylation-induced GSK-3β activation 0:40 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 9 77 theme cardiac 1731:1737 arg1 hypertrophy 1739:1749 cardiac hypertrophy 1731:1749 cardiac hypertrophy 1731:1749 Our findings may provide a new therapeutic strategy for cardiac hypertrophy and subsequent heart failure. 37033243 1 78 theme proteins 321:328 arg1 proteins 321:328 proteins 321:328 proteins 321:328 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 1 78 theme proteins 321:328 arg1 residues 309:316 the serine/threonine residues 288:316 the serine/threonine residues of proteins 288:328 O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. 37033243 6 79 theme GSK-3β 992:997 arg1 O-GlcNAcylation 973:987 O-GlcNAcylation 973:987 O-GlcNAcylation of GSK-3β at Ser9 973:1005 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 3 80 theme subsequent 522:531 arg1 failure 539:545 subsequent heart failure 522:545 subsequent heart failure 522:545 To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. 37033243 0 81 theme overload-induced 64:79 arg1 failure 87:93 pressure overload-induced heart failure 55:93 pressure overload-induced heart failure 55:93 O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. 37033243 4 82 dep weeks 664:668 arg1 TAC 676:678 TAC 676:678 TAC (TAC4W) 676:686 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 4 82 dep weeks 664:668 arg1 TAC4W 681:685 TAC4W 681:685 TAC4W 681:685 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 7 83 from TAC4W 1288:1292 arg1 mice 1304:1307 Ogt-Tg mice 1297:1307 Ogt-Tg mice 1297:1307 Finally, the thinned LV wall and reduced cardiac function induced by TAC4W in Ogt-Tg mice was reversed by the treatment of a GSK-3β inhibitor, TDZD-8. 37033243 9 84 theme heart 1766:1770 arg1 failure 1772:1778 subsequent heart failure 1755:1778 subsequent heart failure 1755:1778 Our findings may provide a new therapeutic strategy for cardiac hypertrophy and subsequent heart failure. 37033243 6 85 from Ser9 1054:1057 arg1 phosphorylation 1025:1039 phosphorylation 1025:1039 phosphorylation of GSK-3β at Ser9 1025:1057 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 8 86 theme compensatory 1490:1501 arg1 hypertrophy 1511:1521 compensatory cardiac hypertrophy 1490:1521 compensatory cardiac hypertrophy 1490:1521 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 4 87 theme ANP 813:815 arg1 levels 817:822 increased ANP levels 803:822 increased ANP levels 803:822 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 2 88 theme cardiac 371:377 arg1 remodeling 379:388 cardiac remodeling 371:388 cardiac remodeling 371:388 However, the role of O-GlcNAcylation in cardiac remodeling and function is not fully understood. 37033243 8 89 theme hypertrophy 1511:1521 arg1 lack 1482:1485 a lack 1480:1485 a lack of compensatory cardiac hypertrophy 1480:1521 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 2 90 theme O-GlcNAcylation 352:366 arg1 role 344:347 the role 340:347 the role of O-GlcNAcylation in cardiac remodeling and function 340:401 However, the role of O-GlcNAcylation in cardiac remodeling and function is not fully understood. 37033243 6 91 theme GSK-3β 1044:1049 arg1 phosphorylation 1025:1039 phosphorylation 1025:1039 phosphorylation of GSK-3β at Ser9 1025:1057 Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3β at Ser9 was increased and phosphorylation of GSK-3β at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. 37033243 4 92 theme fractional 777:786 arg1 shortening 788:797 reduced fractional shortening 769:797 reduced fractional shortening 769:797 Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). 37033243 8 93 theme GSK-3β 1597:1602 arg1 GSK-3β 1597:1602 GSK-3β 1597:1602 GSK-3β 1597:1602 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 37033243 8 93 theme GSK-3β 1597:1602 arg1 site 1589:1592 the phosphorylation site 1569:1592 the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy 1569:1672 These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3β, which deprives the phosphorylation site of GSK-3β to constantly inactivate NFAT activity to prevent cardiac hypertrophy. 36757100 0 0 theme methoxy 61:67 arg1 pyrimidines 69:79 Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines 25:79 Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators 25:158 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 0 0 theme methoxy 61:67 arg1 1,2,3-Triazol-4-yl 42:59 1,2,3-Triazol-4-yl 42:59 1,2,3-Triazol-4-yl 42:59 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 5 1 theme mg/kg 1125:1129 arg1 ED50 1113:1116 an ED50 1110:1116 an ED50 of 1.7 mg/kg 1110:1129 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 2 2 theme heterocycles 344:355 arg1 Exploration 298:308 Exploration 298:308 Exploration of several five- and six-membered heterocycles 298:355 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 3 3 theme undesired 692:700 arg1 metabolites 713:723 undesired saturating metabolites 692:723 undesired saturating metabolites 692:723 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 2 4 theme six-membered 331:342 arg1 heterocycles 344:355 six-membered heterocycles 331:355 six-membered heterocycles 331:355 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 1 5 theme methoxy 229:235 arg1 1,2,3-triazol-4-yl 210:227 1,2,3-triazol-4-yl 210:227 1,2,3-triazol-4-yl 210:227 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 1 5 theme methoxy 229:235 arg1 pyrimidines 237:247 substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines 193:247 substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators 193:295 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 0 6 theme pyrimidines 69:79 arg1 Series 15:20 a Series 13:20 a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators 13:158 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 3 7 theme saturating 702:711 arg1 metabolites 713:723 undesired saturating metabolites 692:723 undesired saturating metabolites 692:723 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 4 8 theme GluN2B 919:924 arg1 affinity 935:942 high GluN2B receptor affinity 914:942 high GluN2B receptor affinity 914:942 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 3 9 theme metabolite 540:549 arg1 studies 566:572 early metabolite identification studies 534:572 early metabolite identification studies 534:572 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 4 10 theme clean 972:976 arg1 profile 993:999 a clean cardiovascular profile 970:999 a clean cardiovascular profile 970:999 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 4 11 theme high 914:917 arg1 affinity 935:942 high GluN2B receptor affinity 914:942 high GluN2B receptor affinity 914:942 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 3 12 theme identification 551:564 arg1 studies 566:572 early metabolite identification studies 534:572 early metabolite identification studies 534:572 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 1 13 theme pyrimidines 237:247 arg1 series 183:188 a series 181:188 a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators 181:295 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 0 14 theme Brain 84:88 arg1 Penetrants 90:99 Brain Penetrants 84:99 Brain Penetrants 84:99 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 4 15 theme compound 882:889 arg1 identification 864:877 the identification 860:877 the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile 860:999 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 4 16 theme 1H-1,2,3-triazol-4-yl 806:826 arg1 pyrimidines 836:846 the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines 802:846 the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines 802:846 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 2 17 theme O-linked 386:393 arg1 analogues 406:414 O-linked pyrimidine analogues 386:414 O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles 386:478 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 3 18 theme early 534:538 arg1 studies 566:572 early metabolite identification studies 534:572 early metabolite identification studies 534:572 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 2 19 theme potency 444:450 arg1 balance 433:439 a balance 431:439 a balance of potency and desirable ADME profiles 431:478 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 2 20 dep potency 444:450 arg1 profiles 471:478 ADME profiles 466:478 ADME profiles 466:478 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 5 21 theme ex 1033:1034 arg1 study 1059:1063 an ex vivo target engagement study 1030:1063 an ex vivo target engagement study in rats at a 10 mg/kg oral dose 1030:1095 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 4 22 theme receptor 926:933 arg1 affinity 935:942 high GluN2B receptor affinity 914:942 high GluN2B receptor affinity 914:942 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 5 23 theme 10 1078:1079 arg1 mg/kg 1081:1085 mg/kg 1081:1085 mg/kg 1081:1085 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 4 24 theme substitution 761:772 arg1 investigation 744:756 The comprehensive investigation 726:756 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines 726:846 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 5 25 from study 1059:1063 arg1 rats 1068:1071 rats 1068:1071 rats at a 10 mg/kg oral dose 1068:1095 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 5 25 from study 1059:1063 arg1 dose 1092:1095 a 10 mg/kg oral dose 1076:1095 a 10 mg/kg oral dose 1076:1095 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 0 26 theme Series 15:20 arg1 Discovery 0:8 Discovery 0:8 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 0:159 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 1 27 theme potent 252:257 arg1 modulators 286:295 potent GluN2B negative allosteric modulators 252:295 potent GluN2B negative allosteric modulators 252:295 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 4 28 theme pyrimidine 781:790 arg1 moiety 792:797 the pyrimidine moiety 777:797 the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines 777:846 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 2 29 theme pyrimidine 395:404 arg1 analogues 406:414 O-linked pyrimidine analogues 386:414 O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles 386:478 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 1 30 theme GluN2B 259:264 arg1 modulators 286:295 potent GluN2B negative allosteric modulators 252:295 potent GluN2B negative allosteric modulators 252:295 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 5 31 theme mg/kg 1081:1085 arg1 dose 1092:1095 a 10 mg/kg oral dose 1076:1095 a 10 mg/kg oral dose 1076:1095 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 3 32 theme initial 488:494 arg1 observations 496:507 initial observations 488:507 initial observations of metabolic saturation 488:531 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 3 33 theme iterative 635:643 arg1 efforts 658:664 further iterative optimization efforts 627:664 further iterative optimization efforts 627:664 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 0 34 theme Substituted 25:35 arg1 pyrimidines 69:79 Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines 25:79 Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators 25:158 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 0 34 theme Substituted 25:35 arg1 1,2,3-Triazol-4-yl 42:59 1,2,3-Triazol-4-yl 42:59 1,2,3-Triazol-4-yl 42:59 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 1 35 theme negative 266:273 arg1 modulators 286:295 potent GluN2B negative allosteric modulators 252:295 potent GluN2B negative allosteric modulators 252:295 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 0 36 theme GluN2B-Selective 112:127 arg1 Modulators 149:158 Potent GluN2B-Selective Negative Allosteric Modulators 105:158 Potent GluN2B-Selective Negative Allosteric Modulators 105:158 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 5 37 theme oral 1087:1090 arg1 dose 1092:1095 a 10 mg/kg oral dose 1076:1095 a 10 mg/kg oral dose 1076:1095 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 5 38 theme target 1041:1046 arg1 study 1059:1063 an ex vivo target engagement study 1030:1063 an ex vivo target engagement study in rats at a 10 mg/kg oral dose 1030:1095 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 2 39 theme analogues 406:414 arg1 identification 368:381 the identification 364:381 the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles 364:478 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 2 40 theme ADME 466:469 arg1 profiles 471:478 ADME profiles 466:478 ADME profiles 466:478 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 1 41 theme allosteric 275:284 arg1 modulators 286:295 potent GluN2B negative allosteric modulators 252:295 potent GluN2B negative allosteric modulators 252:295 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 0 42 theme Potent 105:110 arg1 Modulators 149:158 Potent GluN2B-Selective Negative Allosteric Modulators 105:158 Potent GluN2B-Selective Negative Allosteric Modulators 105:158 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 2 43 link O-linked 386:393 arg1 analogues 406:414 O-linked pyrimidine analogues 386:414 O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles 386:478 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 5 44 theme engagement 1048:1057 arg1 study 1059:1063 an ex vivo target engagement study 1030:1063 an ex vivo target engagement study in rats at a 10 mg/kg oral dose 1030:1095 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 1 45 theme substituted 193:203 arg1 1,2,3-triazol-4-yl 210:227 1,2,3-triazol-4-yl 210:227 1,2,3-triazol-4-yl 210:227 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 1 45 theme substituted 193:203 arg1 pyrimidines 237:247 substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines 193:247 substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators 193:295 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 2 46 theme desirable 456:464 arg1 balance 433:439 a balance 431:439 a balance of potency and desirable ADME profiles 431:478 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 4 47 theme cardiovascular 978:991 arg1 profile 993:999 a clean cardiovascular profile 970:999 a clean cardiovascular profile 970:999 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 0 48 theme Allosteric 138:147 arg1 Modulators 149:158 Potent GluN2B-Selective Negative Allosteric Modulators 105:158 Potent GluN2B-Selective Negative Allosteric Modulators 105:158 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 3 49 theme optimization 645:656 arg1 efforts 658:664 further iterative optimization efforts 627:664 further iterative optimization efforts 627:664 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 4 50 theme comprehensive 730:742 arg1 investigation 744:756 The comprehensive investigation 726:756 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines 726:846 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 0 51 theme 1H- 37:39 arg1 pyrimidines 69:79 Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines 25:79 Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators 25:158 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 0 51 theme 1H- 37:39 arg1 1,2,3-Triazol-4-yl 42:59 1,2,3-Triazol-4-yl 42:59 1,2,3-Triazol-4-yl 42:59 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 0 52 theme Negative 129:136 arg1 Modulators 149:158 Potent GluN2B-Selective Negative Allosteric Modulators 105:158 Potent GluN2B-Selective Negative Allosteric Modulators 105:158 Discovery of a Series of Substituted 1H-((1,2,3-Triazol-4-yl)methoxy)pyrimidines as Brain Penetrants and Potent GluN2B-Selective Negative Allosteric Modulators. 36757100 2 53 theme five- 321:325 arg1 Exploration 298:308 Exploration 298:308 Exploration of several five- and six-membered heterocycles 298:355 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 4 54 theme improved 945:952 arg1 solubility 954:963 improved solubility 945:963 improved solubility 945:963 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 4 55 theme methoxy 828:834 arg1 pyrimidines 836:846 the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines 802:846 the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines 802:846 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 4 56 from investigation 744:756 arg1 moiety 792:797 the pyrimidine moiety 777:797 the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines 777:846 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 1 57 theme 1H- 205:207 arg1 1,2,3-triazol-4-yl 210:227 1,2,3-triazol-4-yl 210:227 1,2,3-triazol-4-yl 210:227 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 1 57 theme 1H- 205:207 arg1 pyrimidines 237:247 substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines 193:247 substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators 193:295 Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. 36757100 3 58 theme further 627:633 arg1 efforts 658:664 further iterative optimization efforts 627:664 further iterative optimization efforts 627:664 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 2 59 contain possessed 421:429 arg1 analogues 406:414 O-linked pyrimidine analogues 386:414 O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles 386:478 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 2 59 contain possessed 421:429 arg2 balance 433:439 a balance 431:439 a balance of potency and desirable ADME profiles 431:478 Exploration of several five- and six-membered heterocycles led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. 36757100 4 60 theme pyrimidines 836:846 arg1 moiety 792:797 the pyrimidine moiety 777:797 the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines 777:846 The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. 36757100 5 61 dep ex 1033:1034 arg1 vivo 1036:1039 vivo 1036:1039 vivo 1036:1039 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 3 62 theme metabolic 512:520 arg1 saturation 522:531 metabolic saturation 512:531 metabolic saturation 512:531 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 5 63 from dose 1092:1095 arg1 rats 1068:1071 rats 1068:1071 rats at a 10 mg/kg oral dose 1068:1095 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 5 63 from dose 1092:1095 arg1 study 1059:1063 an ex vivo target engagement study 1030:1063 an ex vivo target engagement study in rats at a 10 mg/kg oral dose 1030:1095 Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg. 36757100 3 64 theme metabolites 713:723 arg1 formation 679:687 the formation 675:687 the formation of undesired saturating metabolites 675:723 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36757100 3 65 theme saturation 522:531 arg1 observations 496:507 initial observations 488:507 initial observations of metabolic saturation 488:531 Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. 36731797 4 0 theme formation 698:706 arg1 regulation 680:689 regulation 680:689 regulation of CCP formation 680:706 The diversity of functions of cell surface proteins controlled via internalization by CME may suggest that regulation of CCP formation could be effective to allow cellular adaptation under different contexts. 36731797 9 1 theme CCP 1426:1428 arg1 initiation 1430:1439 CCP initiation 1426:1439 CCP initiation 1426:1439 We identify that CCP initiation and the assembly of clathrin and other proteins within CCPs are controlled by O-GlcNAc protein modification. 36731797 10 2 theme endocytosis 1678:1688 arg1 regulation 1640:1649 the important reciprocal regulation 1615:1649 the important reciprocal regulation of cellular metabolism and endocytosis 1615:1688 This reveals a new dimension of regulation of CME and highlights the important reciprocal regulation of cellular metabolism and endocytosis. 36731797 2 3 theme membrane 338:345 arg1 leaflet 316:322 the inner leaflet 306:322 the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs) 306:378 CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). 36731797 3 4 from membrane 531:538 arg1 scission 506:513 scission 506:513 scission from the plasma membrane to yield intracellular vesicles 506:570 These structures recruit specific cargo destined for internalization, generate membrane curvature, and in many cases undergo scission from the plasma membrane to yield intracellular vesicles. 36731797 0 5 theme pits 114:117 arg1 formation 85:93 the formation 81:93 the formation of clathrin-coated pits 81:117 O-GlcNAc transferase modulates the cellular endocytosis machinery by controlling the formation of clathrin-coated pits. 36731797 5 6 attach derived 806:812 arg2 cues 801:804 cues 801:804 cues derived from cellular metabolism 801:837 Of interest is how cues derived from cellular metabolism may regulate CME, given the reciprocal role of CME in controlling cellular metabolism. 36731797 5 6 attach derived 806:812 arg1 metabolism 828:837 cellular metabolism 819:837 cellular metabolism 819:837 Of interest is how cues derived from cellular metabolism may regulate CME, given the reciprocal role of CME in controlling cellular metabolism. 36731797 2 7 theme other 288:292 arg1 proteins 294:301 many other proteins 283:301 many other proteins 283:301 CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). 36731797 1 8 theme Clathrin-mediated 120:136 arg1 CME 151:153 CME 151:153 CME 151:153 Clathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. 36731797 1 8 theme Clathrin-mediated 120:136 arg1 endocytosis 138:148 Clathrin-mediated endocytosis 120:148 Clathrin-mediated endocytosis (CME) 120:154 Clathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. 36731797 4 9 theme functions 590:598 arg1 diversity 577:585 The diversity 573:585 The diversity of functions of cell surface proteins controlled via internalization by CME 573:661 The diversity of functions of cell surface proteins controlled via internalization by CME may suggest that regulation of CCP formation could be effective to allow cellular adaptation under different contexts. 36731797 0 10 theme clathrin-coated 98:112 arg1 pits 114:117 clathrin-coated pits 98:117 clathrin-coated pits 98:117 O-GlcNAc transferase modulates the cellular endocytosis machinery by controlling the formation of clathrin-coated pits. 36731797 4 11 theme different 762:770 arg1 contexts 772:779 different contexts 762:779 different contexts 762:779 The diversity of functions of cell surface proteins controlled via internalization by CME may suggest that regulation of CCP formation could be effective to allow cellular adaptation under different contexts. 36731797 2 12 theme many 283:286 arg1 proteins 294:301 many other proteins 283:301 many other proteins 283:301 CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). 36731797 8 13 mod modification 1283:1294 arg1 AAK1 1352:1355 the endocytic regulator AAK1 1328:1355 the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification 1328:1406 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 8 13 mod modification 1283:1294 arg3 O-GlcNAc 1274:1281 protein O-GlcNAc modification 1266:1294 protein O-GlcNAc modification 1266:1294 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 8 13 mod modification 1283:1294 arg3 protein 1266:1272 protein O-GlcNAc modification 1266:1294 protein O-GlcNAc modification 1266:1294 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 4 14 theme CCP 694:696 arg1 formation 698:706 CCP formation 694:706 CCP formation 694:706 The diversity of functions of cell surface proteins controlled via internalization by CME may suggest that regulation of CCP formation could be effective to allow cellular adaptation under different contexts. 36731797 5 15 theme cellular 905:912 arg1 metabolism 914:923 cellular metabolism 905:923 cellular metabolism 905:923 Of interest is how cues derived from cellular metabolism may regulate CME, given the reciprocal role of CME in controlling cellular metabolism. 36731797 7 16 theme CCP 1186:1188 arg1 formation 1190:1198 CCP formation 1186:1198 CCP formation 1186:1198 Here, we examined how the modification of proteins with O-GlcNAc may control CCP formation and thus CME. 36731797 4 17 theme cellular 736:743 arg1 adaptation 745:754 cellular adaptation 736:754 cellular adaptation 736:754 The diversity of functions of cell surface proteins controlled via internalization by CME may suggest that regulation of CCP formation could be effective to allow cellular adaptation under different contexts. 36731797 8 18 theme protein 1266:1272 arg1 modification 1283:1294 protein O-GlcNAc modification 1266:1294 protein O-GlcNAc modification 1266:1294 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 8 19 theme regulator 1342:1350 arg1 AAK1 1352:1355 the endocytic regulator AAK1 1328:1355 the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification 1328:1406 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 9 20 theme other 1474:1478 arg1 proteins 1480:1487 other proteins 1474:1487 other proteins 1474:1487 We identify that CCP initiation and the assembly of clathrin and other proteins within CCPs are controlled by O-GlcNAc protein modification. 36731797 10 21 theme cellular 1654:1661 arg1 metabolism 1663:1672 cellular metabolism 1654:1672 cellular metabolism 1654:1672 This reveals a new dimension of regulation of CME and highlights the important reciprocal regulation of cellular metabolism and endocytosis. 36731797 2 22 theme clathrin 270:277 arg1 assembly 258:265 the assembly 254:265 the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs) 254:378 CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). 36731797 10 23 theme metabolism 1663:1672 arg1 regulation 1640:1649 the important reciprocal regulation 1615:1649 the important reciprocal regulation of cellular metabolism and endocytosis 1615:1688 This reveals a new dimension of regulation of CME and highlights the important reciprocal regulation of cellular metabolism and endocytosis. 36731797 6 24 dep different 1077:1085 arg1 metabolic 1087:1095 metabolic 1087:1095 metabolic 1087:1095 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 10 25 theme important 1619:1627 arg1 regulation 1640:1649 the important reciprocal regulation 1615:1649 the important reciprocal regulation of cellular metabolism and endocytosis 1615:1688 This reveals a new dimension of regulation of CME and highlights the important reciprocal regulation of cellular metabolism and endocytosis. 36731797 3 26 dep recruit 398:404 arg1 undergo 498:504 undergo 498:504 undergo scission from the plasma membrane to yield intracellular vesicles 498:570 These structures recruit specific cargo destined for internalization, generate membrane curvature, and in many cases undergo scission from the plasma membrane to yield intracellular vesicles. 36731797 1 27 dep internalization 169:183 arg1 the 165:167 the 165:167 the 165:167 Clathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. 36731797 5 28 theme reciprocal 867:876 arg1 role 878:881 the reciprocal role 863:881 the reciprocal role of CME in controlling cellular metabolism 863:923 Of interest is how cues derived from cellular metabolism may regulate CME, given the reciprocal role of CME in controlling cellular metabolism. 36731797 0 29 theme O-GlcNAc 0:7 arg1 transferase 9:19 O-GlcNAc transferase 0:19 O-GlcNAc transferase 0:19 O-GlcNAc transferase modulates the cellular endocytosis machinery by controlling the formation of clathrin-coated pits. 36731797 3 30 theme intracellular 549:561 arg1 vesicles 563:570 intracellular vesicles 549:570 intracellular vesicles 549:570 These structures recruit specific cargo destined for internalization, generate membrane curvature, and in many cases undergo scission from the plasma membrane to yield intracellular vesicles. 36731797 8 31 theme responsible 1250:1260 arg1 enzymes 1242:1248 key enzymes 1238:1248 key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification 1238:1406 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 2 32 theme inner 310:314 arg1 leaflet 316:322 the inner leaflet 306:322 the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs) 306:378 CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). 36731797 7 33 with modification 1135:1146 arg1 O-GlcNAc 1165:1172 O-GlcNAc 1165:1172 O-GlcNAc 1165:1172 Here, we examined how the modification of proteins with O-GlcNAc may control CCP formation and thus CME. 36731797 1 34 theme wide 203:206 arg1 range 208:212 a wide range 201:212 a wide range of cell surface proteins 201:237 Clathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. 36731797 5 35 theme cellular 819:826 arg1 metabolism 828:837 cellular metabolism 819:837 cellular metabolism 819:837 Of interest is how cues derived from cellular metabolism may regulate CME, given the reciprocal role of CME in controlling cellular metabolism. 36731797 8 36 theme specific 1308:1315 arg1 mutants 1317:1323 specific mutants 1308:1323 specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification 1308:1406 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 8 37 theme endocytic 1332:1340 arg1 AAK1 1352:1355 the endocytic regulator AAK1 1328:1355 the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification 1328:1406 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 1 38 theme range 208:212 arg1 function 189:196 function 189:196 function 189:196 Clathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. 36731797 1 38 theme range 208:212 arg1 internalization 169:183 internalization 169:183 internalization 169:183 Clathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. 36731797 6 39 with modification 930:941 arg1 β-N-acetylglucosamine 969:989 O-linked β-N-acetylglucosamine 960:989 O-linked β-N-acetylglucosamine (O-GlcNAc) 960:1000 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 6 39 with modification 930:941 arg1 O-GlcNAc 992:999 O-GlcNAc 992:999 O-GlcNAc 992:999 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 4 40 theme cell 603:606 arg1 proteins 616:623 cell surface proteins 603:623 cell surface proteins controlled via internalization by CME 603:661 The diversity of functions of cell surface proteins controlled via internalization by CME may suggest that regulation of CCP formation could be effective to allow cellular adaptation under different contexts. 36731797 2 41 theme proteins 294:301 arg1 assembly 258:265 the assembly 254:265 the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs) 254:378 CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). 36731797 8 42 theme O-GlcNAc 1274:1281 arg1 modification 1283:1294 protein O-GlcNAc modification 1266:1294 protein O-GlcNAc modification 1266:1294 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 0 43 theme endocytosis 44:54 arg1 machinery 56:64 the cellular endocytosis machinery 31:64 the cellular endocytosis machinery 31:64 O-GlcNAc transferase modulates the cellular endocytosis machinery by controlling the formation of clathrin-coated pits. 36731797 6 44 theme O-linked 960:967 arg1 β-N-acetylglucosamine 969:989 O-linked β-N-acetylglucosamine 960:989 O-linked β-N-acetylglucosamine (O-GlcNAc) 960:1000 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 6 44 theme O-linked 960:967 arg1 O-GlcNAc 992:999 O-GlcNAc 992:999 O-GlcNAc 992:999 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 6 45 theme cellular 1054:1061 arg1 adaptation 1063:1072 cellular adaptation 1054:1072 cellular adaptation to different metabolic conditions 1054:1106 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 2 46 from assembly 258:265 arg1 leaflet 316:322 the inner leaflet 306:322 the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs) 306:378 CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). 36731797 1 47 theme cell 217:220 arg1 proteins 230:237 cell surface proteins 217:237 cell surface proteins 217:237 Clathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. 36731797 0 48 theme cellular 35:42 arg1 machinery 56:64 the cellular endocytosis machinery 31:64 the cellular endocytosis machinery 31:64 O-GlcNAc transferase modulates the cellular endocytosis machinery by controlling the formation of clathrin-coated pits. 36731797 3 49 theme specific 406:413 arg1 cargo 415:419 specific cargo 406:419 specific cargo destined for internalization 406:448 These structures recruit specific cargo destined for internalization, generate membrane curvature, and in many cases undergo scission from the plasma membrane to yield intracellular vesicles. 36731797 6 50 link O-linked 960:967 arg1 β-N-acetylglucosamine 969:989 O-linked β-N-acetylglucosamine 960:989 O-linked β-N-acetylglucosamine (O-GlcNAc) 960:1000 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 6 50 link O-linked 960:967 arg1 O-GlcNAc 992:999 O-GlcNAc 992:999 O-GlcNAc 992:999 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 1 51 theme surface 222:228 arg1 proteins 230:237 cell surface proteins 217:237 cell surface proteins 217:237 Clathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. 36731797 7 52 theme proteins 1151:1158 arg1 modification 1135:1146 the modification 1131:1146 the modification of proteins with O-GlcNAc 1131:1172 Here, we examined how the modification of proteins with O-GlcNAc may control CCP formation and thus CME. 36731797 6 53 theme proteins 946:953 arg1 sensitive 1005:1013 sensitive 1005:1013 sensitive 1005:1013 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 6 53 theme proteins 946:953 arg1 modification 930:941 The modification 926:941 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) 926:1000 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 10 54 theme CME 1596:1598 arg1 regulation 1582:1591 regulation 1582:1591 regulation of CME 1582:1598 This reveals a new dimension of regulation of CME and highlights the important reciprocal regulation of cellular metabolism and endocytosis. 36731797 10 55 theme new 1565:1567 arg1 dimension 1569:1577 a new dimension 1563:1577 a new dimension of regulation of CME 1563:1598 This reveals a new dimension of regulation of CME and highlights the important reciprocal regulation of cellular metabolism and endocytosis. 36731797 2 56 theme plasma 331:336 arg1 membrane 338:345 the plasma membrane 327:345 the plasma membrane into clathrin-coated pits (CCPs) 327:378 CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). 36731797 9 57 theme O-GlcNAc 1519:1526 arg1 modification 1536:1547 O-GlcNAc protein modification 1519:1547 O-GlcNAc protein modification 1519:1547 We identify that CCP initiation and the assembly of clathrin and other proteins within CCPs are controlled by O-GlcNAc protein modification. 36731797 9 58 theme proteins 1480:1487 arg1 initiation 1430:1439 CCP initiation 1426:1439 CCP initiation 1426:1439 We identify that CCP initiation and the assembly of clathrin and other proteins within CCPs are controlled by O-GlcNAc protein modification. 36731797 9 58 theme proteins 1480:1487 arg1 assembly 1449:1456 the assembly 1445:1456 the assembly of clathrin and other proteins within CCPs 1445:1499 We identify that CCP initiation and the assembly of clathrin and other proteins within CCPs are controlled by O-GlcNAc protein modification. 36731797 3 59 theme many 487:490 arg1 cases 492:496 many cases 487:496 many cases 487:496 These structures recruit specific cargo destined for internalization, generate membrane curvature, and in many cases undergo scission from the plasma membrane to yield intracellular vesicles. 36731797 8 60 used used 1217:1220 arg2 We 1214:1215 We 1214:1215 We 1214:1215 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 8 61 theme O-GlcNAc 1386:1393 arg1 modification 1395:1406 O-GlcNAc modification 1386:1406 O-GlcNAc modification 1386:1406 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 10 62 theme regulation 1582:1591 arg1 dimension 1569:1577 a new dimension 1563:1577 a new dimension of regulation of CME 1563:1598 This reveals a new dimension of regulation of CME and highlights the important reciprocal regulation of cellular metabolism and endocytosis. 36731797 1 63 theme proteins 230:237 arg1 range 208:212 a wide range 201:212 a wide range of cell surface proteins 201:237 Clathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. 36731797 3 64 theme plasma 524:529 arg1 membrane 531:538 the plasma membrane 520:538 the plasma membrane 520:538 These structures recruit specific cargo destined for internalization, generate membrane curvature, and in many cases undergo scission from the plasma membrane to yield intracellular vesicles. 36731797 6 65 theme different 1077:1085 arg1 conditions 1097:1106 different metabolic conditions 1077:1106 different metabolic conditions 1077:1106 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 5 66 theme CME 886:888 arg1 role 878:881 the reciprocal role 863:881 the reciprocal role of CME in controlling cellular metabolism 863:923 Of interest is how cues derived from cellular metabolism may regulate CME, given the reciprocal role of CME in controlling cellular metabolism. 36731797 8 67 theme AAK1 1352:1355 arg1 modification 1283:1294 protein O-GlcNAc modification 1266:1294 protein O-GlcNAc modification 1266:1294 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 8 67 theme AAK1 1352:1355 arg1 mutants 1317:1323 specific mutants 1308:1323 specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification 1308:1406 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 10 68 theme reciprocal 1629:1638 arg1 regulation 1640:1649 the important reciprocal regulation 1615:1649 the important reciprocal regulation of cellular metabolism and endocytosis 1615:1688 This reveals a new dimension of regulation of CME and highlights the important reciprocal regulation of cellular metabolism and endocytosis. 36731797 3 69 theme membrane 460:467 arg1 curvature 469:477 membrane curvature 460:477 membrane curvature 460:477 These structures recruit specific cargo destined for internalization, generate membrane curvature, and in many cases undergo scission from the plasma membrane to yield intracellular vesicles. 36731797 9 70 theme protein 1528:1534 arg1 modification 1536:1547 O-GlcNAc protein modification 1519:1547 O-GlcNAc protein modification 1519:1547 We identify that CCP initiation and the assembly of clathrin and other proteins within CCPs are controlled by O-GlcNAc protein modification. 36731797 8 71 theme enzymes 1242:1248 arg1 perturbation 1222:1233 perturbation 1222:1233 perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification 1222:1406 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 4 72 theme proteins 616:623 arg1 functions 590:598 functions 590:598 functions of cell surface proteins controlled via internalization by CME 590:661 The diversity of functions of cell surface proteins controlled via internalization by CME may suggest that regulation of CCP formation could be effective to allow cellular adaptation under different contexts. 36731797 8 73 theme key 1238:1240 arg1 enzymes 1242:1248 key enzymes 1238:1248 key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification 1238:1406 We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. 36731797 9 74 theme clathrin 1461:1468 arg1 initiation 1430:1439 CCP initiation 1426:1439 CCP initiation 1426:1439 We identify that CCP initiation and the assembly of clathrin and other proteins within CCPs are controlled by O-GlcNAc protein modification. 36731797 9 74 theme clathrin 1461:1468 arg1 assembly 1449:1456 the assembly 1445:1456 the assembly of clathrin and other proteins within CCPs 1445:1499 We identify that CCP initiation and the assembly of clathrin and other proteins within CCPs are controlled by O-GlcNAc protein modification. 36731797 6 75 theme nutrient 1018:1025 arg1 availability 1027:1038 nutrient availability 1018:1038 nutrient availability 1018:1038 The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. 36731797 2 76 theme clathrin-coated 352:366 arg1 CCPs 374:377 CCPs 374:377 CCPs 374:377 CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). 36731797 2 76 theme clathrin-coated 352:366 arg1 pits 368:371 clathrin-coated pits 352:371 clathrin-coated pits (CCPs) 352:378 CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). 36731797 4 77 theme surface 608:614 arg1 proteins 616:623 cell surface proteins 603:623 cell surface proteins controlled via internalization by CME 603:661 The diversity of functions of cell surface proteins controlled via internalization by CME may suggest that regulation of CCP formation could be effective to allow cellular adaptation under different contexts. 35571423 11 0 theme PH 1304:1305 arg1 domains 1307:1313 dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) 1299:1422 dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) 1299:1422 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 5 1 theme mutation 666:673 arg1 genes 675:679 the shared mutation genes 655:679 the shared mutation genes in the 9 patients 655:697 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 10 2 theme MUC4 1153:1156 arg1 genes 1169:1173 the keratin 18 (KRT18), MUC4, and MUC3A genes 1129:1173 the keratin 18 (KRT18), MUC4, and MUC3A genes 1129:1173 After searching the TiGER database, the keratin 18 (KRT18), MUC4, and MUC3A genes were found to be significantly more highly expressed in the colon tissues than the other tissues. 35571423 5 3 dep analysis 594:601 arg1 analysis 643:650 analysis 643:650 analysis of the shared mutation genes in the 9 patients 643:697 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 14 4 theme pathological 1855:1866 arg1 mechanism 1868:1876 the potential pathological mechanism 1841:1876 the potential pathological mechanism of vascular intestinal obstruction 1841:1911 Our findings extend understandings of the potential pathological mechanism of vascular intestinal obstruction. 35571423 7 5 theme mutation 845:852 arg1 genes 854:858 112 mutation genes 841:858 112 mutation genes 841:858 Results In total, all 9 patients shared 112 mutation genes. 35571423 12 6 theme vascular 1537:1544 arg1 obstruction 1557:1567 the vascular intestinal obstruction 1533:1567 the vascular intestinal obstruction 1533:1567 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 13 7 from deletion 1793:1800 arg1 genes 1731:1735 4 genes 1729:1735 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18) 1729:1775 Conclusions Our study identified multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18), and the CYP2W1 deletion. 35571423 2 8 theme vascular 289:296 arg1 obstruction 309:319 vascular intestinal obstruction 289:319 vascular intestinal obstruction 289:319 This study aimed to identify several mutations associated with vascular intestinal obstruction. 35571423 12 9 theme quantitative 1614:1625 arg1 qRT-PCR 1664:1670 qRT-PCR 1664:1670 qRT-PCR 1664:1670 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 12 9 theme quantitative 1614:1625 arg1 reaction 1654:1661 quantitative real-time polymerase chain reaction 1614:1661 quantitative real-time polymerase chain reaction (qRT-PCR) 1614:1671 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 6 10 theme software 783:790 arg1 kit 796:798 the open-source software CNV kit 767:798 the open-source software CNV kit 767:798 Copy number variations (CNVs) were identified using the open-source software CNV kit. 35571423 12 11 theme polymerase 1637:1646 arg1 qRT-PCR 1664:1670 qRT-PCR 1664:1670 qRT-PCR 1664:1670 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 12 11 theme polymerase 1637:1646 arg1 reaction 1654:1661 quantitative real-time polymerase chain reaction 1614:1661 quantitative real-time polymerase chain reaction (qRT-PCR) 1614:1671 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 12 12 theme expression 1480:1489 arg1 levels 1491:1496 The expression levels 1476:1496 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients 1476:1595 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 11 13 dep domains 1307:1313 arg1 ADAP1 1318:1322 ADAP1 1318:1322 ADAP1 1318:1322 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 11 13 dep domains 1307:1313 arg1 1 1315:1315 1 1315:1315 1 1315:1315 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 11 13 dep domains 1307:1313 arg1 member 1363:1368 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 11 13 dep domains 1307:1313 arg1 TMEM184A 1414:1421 TMEM184A 1414:1421 TMEM184A 1414:1421 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 11 13 dep domains 1307:1313 arg1 184A 1408:1411 transmembrane protein 184A 1386:1411 transmembrane protein 184A (TMEM184A) 1386:1422 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 4 14 from genes 477:481 arg1 patient 491:497 each patient 486:497 each patient 486:497 The mutation genes in each patient and the mutation genes shared by all 9 patients were identified. 35571423 13 15 from mutations 1716:1724 arg1 genes 1731:1735 4 genes 1729:1735 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18) 1729:1775 Conclusions Our study identified multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18), and the CYP2W1 deletion. 35571423 1 16 theme intestinal 145:154 arg1 disease 156:162 a rare intestinal disease 138:162 a rare intestinal disease with a rapid progression, poor prognosis, and high mortality 138:223 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 1 16 theme intestinal 145:154 arg1 obstruction 123:133 Background Vascular intestinal obstruction 92:133 Background Vascular intestinal obstruction 92:133 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 3 17 theme Methods 322:328 arg1 WES 354:356 WES 354:356 WES 354:356 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 3 17 theme Methods 322:328 arg1 sequencing 342:351 Methods Whole-exome sequencing 322:351 Methods Whole-exome sequencing (WES) 322:357 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 2 18 theme several 255:261 arg1 mutations 263:271 several mutations 255:271 several mutations associated with vascular intestinal obstruction 255:319 This study aimed to identify several mutations associated with vascular intestinal obstruction. 35571423 1 19 theme rapid 171:175 arg1 progression 177:187 a rapid progression 169:187 a rapid progression 169:187 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 5 20 theme protein-protein 609:623 arg1 interaction 625:635 a protein-protein interaction 607:635 a protein-protein interaction (PPI) 607:641 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 5 20 theme protein-protein 609:623 arg1 PPI 638:640 PPI 638:640 PPI 638:640 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 12 21 theme control 1580:1586 arg1 patients 1588:1595 the vascular intestinal obstruction and normal control patients 1533:1595 the vascular intestinal obstruction and normal control patients 1533:1595 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 3 22 theme peripheral 380:389 arg1 blood 391:395 the peripheral blood 376:395 the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction 376:461 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 11 23 theme transmembrane 1386:1398 arg1 TMEM184A 1414:1421 TMEM184A 1414:1421 TMEM184A 1414:1421 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 11 23 theme transmembrane 1386:1398 arg1 184A 1408:1411 transmembrane protein 184A 1386:1411 transmembrane protein 184A (TMEM184A) 1386:1422 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 8 24 theme biosynthesis 1012:1023 arg1 pathways 917:924 2 significantly enriched pathways 892:924 2 significantly enriched pathways 892:924 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 8 24 theme biosynthesis 1012:1023 arg1 termination 984:994 the termination 980:994 the termination of the O-glycan biosynthesis 980:1023 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 8 24 theme biosynthesis 1012:1023 arg1 glycosylation 940:952 the O-linked glycosylation 927:952 the O-linked glycosylation of the mucins (MUCs) 927:973 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 11 25 theme subfamily 1351:1359 arg1 member 1363:1368 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 11 26 with ArfGAP 1287:1292 arg1 domains 1307:1313 dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) 1299:1422 dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) 1299:1422 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 6 27 theme Copy 715:718 arg1 number 720:725 Copy number 715:725 Copy number variations (CNVs) 715:743 Copy number variations (CNVs) were identified using the open-source software CNV kit. 35571423 5 28 theme annotation 583:592 arg1 analysis 594:601 a functional annotation analysis 570:601 a functional annotation analysis 570:601 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 1 29 theme Vascular 103:110 arg1 disease 156:162 a rare intestinal disease 138:162 a rare intestinal disease with a rapid progression, poor prognosis, and high mortality 138:223 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 1 29 theme Vascular 103:110 arg1 obstruction 123:133 Background Vascular intestinal obstruction 92:133 Background Vascular intestinal obstruction 92:133 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 12 30 theme intestinal 1546:1555 arg1 obstruction 1557:1567 the vascular intestinal obstruction 1533:1567 the vascular intestinal obstruction 1533:1567 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 3 31 theme sporadic 402:409 arg1 patients 411:418 9 sporadic patients 400:418 9 sporadic patients with acute vascular intestinal obstruction 400:461 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 4 32 theme mutation 507:514 arg1 genes 516:520 the mutation genes 503:520 the mutation genes shared by all 9 patients 503:545 The mutation genes in each patient and the mutation genes shared by all 9 patients were identified. 35571423 11 33 theme P450 1337:1340 arg1 member 1363:1368 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 0 34 theme Molecular 0:8 arg1 characterization 10:25 Molecular characterization 0:25 Molecular characterization of vascular intestinal obstruction 0:60 Molecular characterization of vascular intestinal obstruction using whole-exome sequencing. 35571423 14 35 theme potential 1845:1853 arg1 mechanism 1868:1876 the potential pathological mechanism 1841:1876 the potential pathological mechanism of vascular intestinal obstruction 1841:1911 Our findings extend understandings of the potential pathological mechanism of vascular intestinal obstruction. 35571423 12 36 theme several 1501:1507 arg1 genes 1519:1523 several candidate genes 1501:1523 several candidate genes between the vascular intestinal obstruction and normal control patients 1501:1595 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 10 37 theme colon 1235:1239 arg1 tissues 1241:1247 the colon tissues 1231:1247 the colon tissues 1231:1247 After searching the TiGER database, the keratin 18 (KRT18), MUC4, and MUC3A genes were found to be significantly more highly expressed in the colon tissues than the other tissues. 35571423 12 38 theme genes 1519:1523 arg1 levels 1491:1496 The expression levels 1476:1496 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients 1476:1595 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 3 39 theme vascular 431:438 arg1 obstruction 451:461 acute vascular intestinal obstruction 425:461 acute vascular intestinal obstruction 425:461 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 11 40 theme W 1361:1361 arg1 member 1363:1368 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 0 41 theme intestinal 39:48 arg1 obstruction 50:60 vascular intestinal obstruction 30:60 vascular intestinal obstruction 30:60 Molecular characterization of vascular intestinal obstruction using whole-exome sequencing. 35571423 5 42 from genes 675:679 arg1 patients 690:697 the 9 patients 684:697 the 9 patients 684:697 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 8 43 theme O-linked 931:938 arg1 glycosylation 940:952 the O-linked glycosylation 927:952 the O-linked glycosylation of the mucins (MUCs) 927:973 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 5 44 from patients 690:697 arg1 analysis 643:650 analysis 643:650 analysis of the shared mutation genes in the 9 patients 643:697 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 13 45 dep Conclusions 1674:1684 arg1 identified 1696:1705 identified 1696:1705 identified multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18), and the CYP2W1 deletion 1696:1800 Conclusions Our study identified multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18), and the CYP2W1 deletion. 35571423 8 46 theme mucins 961:966 arg1 pathways 917:924 2 significantly enriched pathways 892:924 2 significantly enriched pathways 892:924 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 8 46 theme mucins 961:966 arg1 termination 984:994 the termination 980:994 the termination of the O-glycan biosynthesis 980:1023 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 8 46 theme mucins 961:966 arg1 glycosylation 940:952 the O-linked glycosylation 927:952 the O-linked glycosylation of the mucins (MUCs) 927:973 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 11 47 theme dual 1299:1302 arg1 domains 1307:1313 dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) 1299:1422 dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) 1299:1422 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 5 48 theme shared 659:664 arg1 genes 675:679 the shared mutation genes 655:679 the shared mutation genes in the 9 patients 655:697 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 8 49 gly glycosylation 940:952 arg1 biosynthesis 1012:1023 the O-glycan biosynthesis 999:1023 the O-glycan biosynthesis 999:1023 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 8 49 gly glycosylation 940:952 arg1 MUCs 969:972 MUCs 969:972 MUCs 969:972 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 8 49 gly glycosylation 940:952 arg1 mucins 961:966 the mucins 957:966 the mucins (MUCs) 957:973 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 13 50 theme CYP2W1 1786:1791 arg1 deletion 1793:1800 the CYP2W1 deletion 1782:1800 the CYP2W1 deletion 1782:1800 Conclusions Our study identified multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18), and the CYP2W1 deletion. 35571423 5 51 theme genes 675:679 arg1 analysis 643:650 analysis 643:650 analysis of the shared mutation genes in the 9 patients 643:697 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 4 52 from genes 516:520 arg1 patient 491:497 each patient 486:497 each patient 486:497 The mutation genes in each patient and the mutation genes shared by all 9 patients were identified. 35571423 2 53 theme intestinal 298:307 arg1 obstruction 309:319 vascular intestinal obstruction 289:319 vascular intestinal obstruction 289:319 This study aimed to identify several mutations associated with vascular intestinal obstruction. 35571423 1 54 theme poor 190:193 arg1 prognosis 195:203 poor prognosis 190:203 poor prognosis 190:203 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 7 55 from Results 801:807 arg1 total 812:816 total 812:816 total 812:816 Results In total, all 9 patients shared 112 mutation genes. 35571423 12 56 theme real-time 1627:1635 arg1 qRT-PCR 1664:1670 qRT-PCR 1664:1670 qRT-PCR 1664:1670 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 12 56 theme real-time 1627:1635 arg1 reaction 1654:1661 quantitative real-time polymerase chain reaction 1614:1661 quantitative real-time polymerase chain reaction (qRT-PCR) 1614:1671 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 6 57 theme CNV 792:794 arg1 kit 796:798 the open-source software CNV kit 767:798 the open-source software CNV kit 767:798 Copy number variations (CNVs) were identified using the open-source software CNV kit. 35571423 12 58 theme chain 1648:1652 arg1 qRT-PCR 1664:1670 qRT-PCR 1664:1670 qRT-PCR 1664:1670 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 12 58 theme chain 1648:1652 arg1 reaction 1654:1661 quantitative real-time polymerase chain reaction 1614:1661 quantitative real-time polymerase chain reaction (qRT-PCR) 1614:1671 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 6 59 theme open-source 771:781 arg1 kit 796:798 the open-source software CNV kit 767:798 the open-source software CNV kit 767:798 Copy number variations (CNVs) were identified using the open-source software CNV kit. 35571423 1 60 theme high 210:213 arg1 mortality 215:223 high mortality 210:223 high mortality 210:223 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 3 61 with patients 411:418 arg1 obstruction 451:461 acute vascular intestinal obstruction 425:461 acute vascular intestinal obstruction 425:461 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 1 62 theme rare 140:143 arg1 disease 156:162 a rare intestinal disease 138:162 a rare intestinal disease with a rapid progression, poor prognosis, and high mortality 138:223 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 1 62 theme rare 140:143 arg1 obstruction 123:133 Background Vascular intestinal obstruction 92:133 Background Vascular intestinal obstruction 92:133 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 5 63 theme functional 572:581 arg1 analysis 594:601 a functional annotation analysis 570:601 a functional annotation analysis 570:601 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 3 64 theme Whole-exome 330:340 arg1 WES 354:356 WES 354:356 WES 354:356 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 3 64 theme Whole-exome 330:340 arg1 sequencing 342:351 Methods Whole-exome sequencing 322:351 Methods Whole-exome sequencing (WES) 322:357 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 4 65 theme mutation 468:475 arg1 genes 477:481 The mutation genes 464:481 The mutation genes in each patient 464:497 The mutation genes in each patient and the mutation genes shared by all 9 patients were identified. 35571423 10 66 theme MUC3A 1163:1167 arg1 genes 1169:1173 the keratin 18 (KRT18), MUC4, and MUC3A genes 1129:1173 the keratin 18 (KRT18), MUC4, and MUC3A genes 1129:1173 After searching the TiGER database, the keratin 18 (KRT18), MUC4, and MUC3A genes were found to be significantly more highly expressed in the colon tissues than the other tissues. 35571423 8 67 link O-linked 931:938 arg1 glycosylation 940:952 the O-linked glycosylation 927:952 the O-linked glycosylation of the mucins (MUCs) 927:973 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 11 68 theme protein 1400:1406 arg1 TMEM184A 1414:1421 TMEM184A 1414:1421 TMEM184A 1414:1421 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 11 68 theme protein 1400:1406 arg1 184A 1408:1411 transmembrane protein 184A 1386:1411 transmembrane protein 184A (TMEM184A) 1386:1422 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 9 69 with protein 1041:1047 arg1 degree 1066:1071 the highest degree 1054:1071 the highest degree in the PPI network 1054:1090 MUC5AC was the protein with the highest degree in the PPI network. 35571423 8 70 theme O-glycan 1003:1010 arg1 biosynthesis 1012:1023 the O-glycan biosynthesis 999:1023 the O-glycan biosynthesis 999:1023 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 14 71 theme obstruction 1901:1911 arg1 mechanism 1868:1876 the potential pathological mechanism 1841:1876 the potential pathological mechanism of vascular intestinal obstruction 1841:1911 Our findings extend understandings of the potential pathological mechanism of vascular intestinal obstruction. 35571423 12 72 theme obstruction 1557:1567 arg1 patients 1588:1595 the vascular intestinal obstruction and normal control patients 1533:1595 the vascular intestinal obstruction and normal control patients 1533:1595 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 14 73 theme intestinal 1890:1899 arg1 obstruction 1901:1911 vascular intestinal obstruction 1881:1911 vascular intestinal obstruction 1881:1911 Our findings extend understandings of the potential pathological mechanism of vascular intestinal obstruction. 35571423 12 74 theme normal 1573:1578 arg1 control 1580:1586 normal control 1573:1586 normal control 1573:1586 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 8 75 theme enriched 908:915 arg1 pathways 917:924 2 significantly enriched pathways 892:924 2 significantly enriched pathways 892:924 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 14 76 theme vascular 1881:1888 arg1 obstruction 1901:1911 vascular intestinal obstruction 1881:1911 vascular intestinal obstruction 1881:1911 Our findings extend understandings of the potential pathological mechanism of vascular intestinal obstruction. 35571423 6 77 theme number 720:725 arg1 CNVs 739:742 CNVs 739:742 CNVs 739:742 Copy number variations (CNVs) were identified using the open-source software CNV kit. 35571423 6 77 theme number 720:725 arg1 variations 727:736 Copy number variations 715:736 Copy number variations (CNVs) 715:743 Copy number variations (CNVs) were identified using the open-source software CNV kit. 35571423 11 78 theme family 1342:1347 arg1 member 1363:1368 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 1 79 with disease 156:162 arg1 mortality 215:223 high mortality 210:223 high mortality 210:223 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 1 79 with disease 156:162 arg1 progression 177:187 a rapid progression 169:187 a rapid progression 169:187 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 1 79 with disease 156:162 arg1 prognosis 195:203 poor prognosis 190:203 poor prognosis 190:203 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 1 80 theme Background 92:101 arg1 disease 156:162 a rare intestinal disease 138:162 a rare intestinal disease with a rapid progression, poor prognosis, and high mortality 138:223 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 1 80 theme Background 92:101 arg1 obstruction 123:133 Background Vascular intestinal obstruction 92:133 Background Vascular intestinal obstruction 92:133 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 9 81 theme highest 1058:1064 arg1 degree 1066:1071 the highest degree 1054:1071 the highest degree in the PPI network 1054:1090 MUC5AC was the protein with the highest degree in the PPI network. 35571423 1 82 theme intestinal 112:121 arg1 disease 156:162 a rare intestinal disease 138:162 a rare intestinal disease with a rapid progression, poor prognosis, and high mortality 138:223 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 1 82 theme intestinal 112:121 arg1 obstruction 123:133 Background Vascular intestinal obstruction 92:133 Background Vascular intestinal obstruction 92:133 Background Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. 35571423 8 83 theme Reactome 865:872 arg1 database 874:881 The Reactome database 861:881 The Reactome database 861:881 The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. 35571423 3 84 theme patients 411:418 arg1 blood 391:395 the peripheral blood 376:395 the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction 376:461 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 0 85 theme vascular 30:37 arg1 obstruction 50:60 vascular intestinal obstruction 30:60 vascular intestinal obstruction 30:60 Molecular characterization of vascular intestinal obstruction using whole-exome sequencing. 35571423 9 86 theme PPI 1080:1082 arg1 network 1084:1090 the PPI network 1076:1090 the PPI network 1076:1090 MUC5AC was the protein with the highest degree in the PPI network. 35571423 0 87 theme obstruction 50:60 arg1 characterization 10:25 Molecular characterization 0:25 Molecular characterization of vascular intestinal obstruction 0:60 Molecular characterization of vascular intestinal obstruction using whole-exome sequencing. 35571423 5 88 from analysis 643:650 arg1 patients 690:697 the 9 patients 684:697 the 9 patients 684:697 Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. 35571423 12 89 theme candidate 1509:1517 arg1 genes 1519:1523 several candidate genes 1501:1523 several candidate genes between the vascular intestinal obstruction and normal control patients 1501:1595 The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 35571423 3 90 theme intestinal 440:449 arg1 obstruction 451:461 acute vascular intestinal obstruction 425:461 acute vascular intestinal obstruction 425:461 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 11 91 theme colon 1461:1465 arg1 tissues 1467:1473 colon tissues 1461:1473 colon tissues 1461:1473 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 0 92 theme whole-exome 68:78 arg1 sequencing 80:89 whole-exome sequencing 68:89 whole-exome sequencing 68:89 Molecular characterization of vascular intestinal obstruction using whole-exome sequencing. 35571423 3 93 theme acute 425:429 arg1 obstruction 451:461 acute vascular intestinal obstruction 425:461 acute vascular intestinal obstruction 425:461 Methods Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. 35571423 10 94 theme other 1258:1262 arg1 tissues 1264:1270 the other tissues 1254:1270 the other tissues 1254:1270 After searching the TiGER database, the keratin 18 (KRT18), MUC4, and MUC3A genes were found to be significantly more highly expressed in the colon tissues than the other tissues. 35571423 10 95 theme TiGER 1113:1117 arg1 database 1119:1126 the TiGER database 1109:1126 the TiGER database 1109:1126 After searching the TiGER database, the keratin 18 (KRT18), MUC4, and MUC3A genes were found to be significantly more highly expressed in the colon tissues than the other tissues. 35571423 13 96 dep MUC3A 1744:1748 arg1 i.e. 1738:1741 i.e. 1738:1741 i.e. 1738:1741 Conclusions Our study identified multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18), and the CYP2W1 deletion. 35571423 14 97 theme mechanism 1868:1876 arg1 understandings 1823:1836 understandings 1823:1836 understandings of the potential pathological mechanism of vascular intestinal obstruction 1823:1911 Our findings extend understandings of the potential pathological mechanism of vascular intestinal obstruction. 35571423 9 98 from degree 1066:1071 arg1 network 1084:1090 the PPI network 1076:1090 the PPI network 1076:1090 MUC5AC was the protein with the highest degree in the PPI network. 35571423 11 99 theme cytochrome 1326:1335 arg1 member 1363:1368 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 cytochrome P450 family 2 subfamily W member 1 (CYP2W1) 1326:1379 Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. 35571423 13 100 theme multiple 1707:1714 arg1 mutations 1716:1724 multiple mutations 1707:1724 multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18) 1707:1775 Conclusions Our study identified multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18), and the CYP2W1 deletion. 35571423 10 101 theme keratin 1133:1139 arg1 genes 1169:1173 the keratin 18 (KRT18), MUC4, and MUC3A genes 1129:1173 the keratin 18 (KRT18), MUC4, and MUC3A genes 1129:1173 After searching the TiGER database, the keratin 18 (KRT18), MUC4, and MUC3A genes were found to be significantly more highly expressed in the colon tissues than the other tissues. 35427441 5 0 theme protein 798:804 arg1 glycosylation 815:827 protein O-linked glycosylation 798:827 protein O-linked glycosylation 798:827 As proof of principle, NbP4H4 was targeted encoding a prolyl-4-hydroxylase involved in protein O-linked glycosylation. 35427441 8 1 theme recombinant 1202:1212 arg1 IgA1 1214:1217 plant-produced recombinant IgA1 1187:1217 plant-produced recombinant IgA1 as a reporter protein 1187:1239 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 9 2 theme N. 1459:1460 arg1 mutants 1474:1480 N. benthamiana mutants 1459:1480 N. benthamiana mutants 1459:1480 The selection of efficient gRNAs combined with the DsRed2 marker reduces the effort needed to generate N. benthamiana mutants and simplifies the screening processes to obtain transgene-free progeny. 35427441 3 3 theme tobacco 500:506 arg1 relative 488:495 an allotetraploid relative 470:495 an allotetraploid relative of tobacco frequently used for transient protein expression 470:555 This is the case for Nicotiana benthamiana, an allotetraploid relative of tobacco frequently used for transient protein expression. 35427441 3 3 theme tobacco 500:506 arg1 benthamiana 457:467 Nicotiana benthamiana 447:467 Nicotiana benthamiana 447:467 This is the case for Nicotiana benthamiana, an allotetraploid relative of tobacco frequently used for transient protein expression. 35427441 5 4 theme O-linked 806:813 arg1 glycosylation 815:827 protein O-linked glycosylation 798:827 protein O-linked glycosylation 798:827 As proof of principle, NbP4H4 was targeted encoding a prolyl-4-hydroxylase involved in protein O-linked glycosylation. 35427441 6 5 theme NbP4H4 966:971 arg1 genes 973:977 all four NbP4H4 genes 957:977 all four NbP4H4 genes 957:977 Using preselected gRNAs with efficiencies confirmed by transient expression, transgenic plant lines with knockout mutations in all four NbP4H4 genes were obtained. 35427441 9 6 theme transgene-free 1531:1544 arg1 progeny 1546:1552 transgene-free progeny 1531:1552 transgene-free progeny 1531:1552 The selection of efficient gRNAs combined with the DsRed2 marker reduces the effort needed to generate N. benthamiana mutants and simplifies the screening processes to obtain transgene-free progeny. 35427441 8 7 theme hydroxyproline 1295:1308 arg1 residues 1310:1317 hydroxyproline residues 1295:1317 hydroxyproline residues 1295:1317 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 6 8 from mutations 944:952 arg1 genes 973:977 all four NbP4H4 genes 957:977 all four NbP4H4 genes 957:977 Using preselected gRNAs with efficiencies confirmed by transient expression, transgenic plant lines with knockout mutations in all four NbP4H4 genes were obtained. 35427441 7 9 from absence 1044:1050 arg1 plants 1082:1087 T1 plants 1079:1087 T1 plants 1079:1087 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 8 10 from changes 1250:1256 arg1 pentoses 1323:1330 pentoses 1323:1330 pentoses 1323:1330 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 8 10 from changes 1250:1256 arg1 peptides 1275:1282 the number of peptides 1261:1282 the number of peptides containing hydroxyproline residues 1261:1317 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 8 10 from changes 1250:1256 arg1 plants 1348:1353 the knockout plants 1335:1353 the knockout plants 1335:1353 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 4 11 theme plants 687:692 arg1 selection 663:671 selection 663:671 selection 663:671 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants was established. 35427441 4 11 theme plants 687:692 arg1 identification 644:657 identification 644:657 identification 644:657 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants was established. 35427441 1 12 theme recombinant 264:274 arg1 proteins 276:283 recombinant proteins 264:283 recombinant proteins 264:283 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 0 13 theme plant 108:112 arg1 selection 114:122 plant selection 108:122 plant selection 108:122 CRISPR/Cas9-mediated knockout of a prolyl-4-hydroxylase subfamily in Nicotiana benthamiana using DsRed2 for plant selection. 35427441 9 14 theme efficient 1373:1381 arg1 gRNAs 1383:1387 efficient gRNAs 1373:1387 efficient gRNAs combined with the DsRed2 marker 1373:1419 The selection of efficient gRNAs combined with the DsRed2 marker reduces the effort needed to generate N. benthamiana mutants and simplifies the screening processes to obtain transgene-free progeny. 35427441 1 15 theme molecular 164:172 arg1 farming 174:180 molecular farming 164:180 molecular farming 164:180 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 1 16 theme proteins 276:283 arg1 quality 243:249 quality 243:249 quality 243:249 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 1 16 theme proteins 276:283 arg1 yield 255:259 yield 255:259 yield 255:259 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 8 17 theme reporter 1224:1231 arg1 protein 1233:1239 a reporter protein 1222:1239 a reporter protein 1222:1239 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 9 18 theme benthamiana 1462:1472 arg1 mutants 1474:1480 N. benthamiana mutants 1459:1480 N. benthamiana mutants 1459:1480 The selection of efficient gRNAs combined with the DsRed2 marker reduces the effort needed to generate N. benthamiana mutants and simplifies the screening processes to obtain transgene-free progeny. 35427441 7 19 theme biallelic 1134:1142 arg1 mutations 1144:1152 homozygous or biallelic mutations 1120:1152 homozygous or biallelic mutations 1120:1152 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 3 20 theme transient 528:536 arg1 expression 546:555 transient protein expression 528:555 transient protein expression 528:555 This is the case for Nicotiana benthamiana, an allotetraploid relative of tobacco frequently used for transient protein expression. 35427441 2 21 theme large 399:403 arg1 genomes 417:423 large and complex genomes 399:423 large and complex genomes 399:423 However, it is often necessary to target multiple genes simultaneously, particularly when using host plants with large and complex genomes. 35427441 0 22 from subfamily 56:64 arg1 benthamiana 79:89 Nicotiana benthamiana 69:89 Nicotiana benthamiana 69:89 CRISPR/Cas9-mediated knockout of a prolyl-4-hydroxylase subfamily in Nicotiana benthamiana using DsRed2 for plant selection. 35427441 8 23 theme number of 1265:1273 arg1 peptides 1275:1282 the number of peptides 1261:1282 the number of peptides containing hydroxyproline residues 1261:1317 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 6 24 theme preselected 836:846 arg1 gRNAs 848:852 preselected gRNAs 836:852 preselected gRNAs with efficiencies confirmed by transient expression 836:904 Using preselected gRNAs with efficiencies confirmed by transient expression, transgenic plant lines with knockout mutations in all four NbP4H4 genes were obtained. 35427441 3 25 theme protein 538:544 arg1 expression 546:555 transient protein expression 528:555 transient protein expression 528:555 This is the case for Nicotiana benthamiana, an allotetraploid relative of tobacco frequently used for transient protein expression. 35427441 4 26 theme transgenic 676:685 arg1 plants 687:692 transgenic plants 676:692 transgenic plants 676:692 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants was established. 35427441 6 27 theme knockout 935:942 arg1 mutations 944:952 knockout mutations 935:952 knockout mutations in all four NbP4H4 genes 935:977 Using preselected gRNAs with efficiencies confirmed by transient expression, transgenic plant lines with knockout mutations in all four NbP4H4 genes were obtained. 35427441 7 28 theme homozygous 1120:1129 arg1 mutations 1144:1152 homozygous or biallelic mutations 1120:1152 homozygous or biallelic mutations 1120:1152 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 7 29 used used 1021:1024 arg2 fluorescence 999:1010 Leaf fluorescence 994:1010 Leaf fluorescence 994:1010 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 6 30 with gRNAs 848:852 arg1 efficiencies 859:870 efficiencies 859:870 efficiencies confirmed by transient expression 859:904 Using preselected gRNAs with efficiencies confirmed by transient expression, transgenic plant lines with knockout mutations in all four NbP4H4 genes were obtained. 35427441 4 31 theme multiplex 560:568 arg1 system 585:590 A multiplex genome editing system 558:590 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants 558:692 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants was established. 35427441 5 32 link O-linked 806:813 arg1 glycosylation 815:827 protein O-linked glycosylation 798:827 protein O-linked glycosylation 798:827 As proof of principle, NbP4H4 was targeted encoding a prolyl-4-hydroxylase involved in protein O-linked glycosylation. 35427441 2 33 theme host 382:385 arg1 plants 387:392 host plants 382:392 host plants with large and complex genomes 382:423 However, it is often necessary to target multiple genes simultaneously, particularly when using host plants with large and complex genomes. 35427441 9 34 theme DsRed2 1407:1412 arg1 marker 1414:1419 the DsRed2 marker 1403:1419 the DsRed2 marker 1403:1419 The selection of efficient gRNAs combined with the DsRed2 marker reduces the effort needed to generate N. benthamiana mutants and simplifies the screening processes to obtain transgene-free progeny. 35427441 5 35 theme principle 723:731 arg1 proof 714:718 proof 714:718 proof of principle 714:731 As proof of principle, NbP4H4 was targeted encoding a prolyl-4-hydroxylase involved in protein O-linked glycosylation. 35427441 5 35 theme principle 723:731 arg1 NbP4H4 734:739 NbP4H4 734:739 NbP4H4 734:739 As proof of principle, NbP4H4 was targeted encoding a prolyl-4-hydroxylase involved in protein O-linked glycosylation. 35427441 1 36 theme CRISPR/Cas9 201:211 arg1 editing 220:226 CRISPR/Cas9 genome editing 201:226 CRISPR/Cas9 genome editing 201:226 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 4 37 theme editing 577:583 arg1 system 585:590 A multiplex genome editing system 558:590 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants 558:692 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants was established. 35427441 1 38 dep quality 243:249 arg1 the 239:241 the 239:241 the 239:241 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 8 39 theme plant-produced 1187:1200 arg1 IgA1 1214:1217 plant-produced recombinant IgA1 1187:1217 plant-produced recombinant IgA1 as a reporter protein 1187:1239 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 1 40 theme genome 213:218 arg1 editing 220:226 CRISPR/Cas9 genome editing 201:226 CRISPR/Cas9 genome editing 201:226 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 0 41 theme subfamily 56:64 arg1 knockout 21:28 knockout 21:28 knockout 21:28 CRISPR/Cas9-mediated knockout of a prolyl-4-hydroxylase subfamily in Nicotiana benthamiana using DsRed2 for plant selection. 35427441 4 42 theme genome 570:575 arg1 system 585:590 A multiplex genome editing system 558:590 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants 558:692 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants was established. 35427441 9 43 theme gRNAs 1383:1387 arg1 selection 1360:1368 The selection 1356:1368 The selection of efficient gRNAs combined with the DsRed2 marker 1356:1419 The selection of efficient gRNAs combined with the DsRed2 marker reduces the effort needed to generate N. benthamiana mutants and simplifies the screening processes to obtain transgene-free progeny. 35427441 7 44 with lines 1109:1113 arg1 mutations 1144:1152 homozygous or biallelic mutations 1120:1152 homozygous or biallelic mutations 1120:1152 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 6 45 with lines 924:928 arg1 mutations 944:952 knockout mutations 935:952 knockout mutations in all four NbP4H4 genes 935:977 Using preselected gRNAs with efficiencies confirmed by transient expression, transgenic plant lines with knockout mutations in all four NbP4H4 genes were obtained. 35427441 2 46 theme complex 409:415 arg1 genomes 417:423 large and complex genomes 399:423 large and complex genomes 399:423 However, it is often necessary to target multiple genes simultaneously, particularly when using host plants with large and complex genomes. 35427441 0 47 theme prolyl-4-hydroxylase 35:54 arg1 subfamily 56:64 a prolyl-4-hydroxylase subfamily 33:64 a prolyl-4-hydroxylase subfamily in Nicotiana benthamiana 33:89 CRISPR/Cas9-mediated knockout of a prolyl-4-hydroxylase subfamily in Nicotiana benthamiana using DsRed2 for plant selection. 35427441 7 48 theme transgene-free 1094:1107 arg1 lines 1109:1113 transgene-free lines 1094:1113 transgene-free lines with homozygous or biallelic mutations 1094:1152 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 6 49 theme plant 918:922 arg1 lines 924:928 transgenic plant lines 907:928 transgenic plant lines with knockout mutations in all four NbP4H4 genes 907:977 Using preselected gRNAs with efficiencies confirmed by transient expression, transgenic plant lines with knockout mutations in all four NbP4H4 genes were obtained. 35427441 8 50 contain containing 1284:1293 arg1 peptides 1275:1282 the number of peptides 1261:1282 the number of peptides containing hydroxyproline residues 1261:1317 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 8 50 contain containing 1284:1293 arg2 residues 1310:1317 hydroxyproline residues 1295:1317 hydroxyproline residues 1295:1317 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 7 51 theme SpCas9 1059:1064 arg1 transgene 1066:1074 the SpCas9 transgene 1055:1074 the SpCas9 transgene in T1 plants 1055:1087 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 3 52 theme Nicotiana 447:455 arg1 relative 488:495 an allotetraploid relative 470:495 an allotetraploid relative of tobacco frequently used for transient protein expression 470:555 This is the case for Nicotiana benthamiana, an allotetraploid relative of tobacco frequently used for transient protein expression. 35427441 3 52 theme Nicotiana 447:455 arg1 benthamiana 457:467 Nicotiana benthamiana 447:467 Nicotiana benthamiana 447:467 This is the case for Nicotiana benthamiana, an allotetraploid relative of tobacco frequently used for transient protein expression. 35427441 0 53 theme Nicotiana 69:77 arg1 benthamiana 79:89 Nicotiana benthamiana 69:89 Nicotiana benthamiana 69:89 CRISPR/Cas9-mediated knockout of a prolyl-4-hydroxylase subfamily in Nicotiana benthamiana using DsRed2 for plant selection. 35427441 6 54 theme transgenic 907:916 arg1 lines 924:928 transgenic plant lines 907:928 transgenic plant lines with knockout mutations in all four NbP4H4 genes 907:977 Using preselected gRNAs with efficiencies confirmed by transient expression, transgenic plant lines with knockout mutations in all four NbP4H4 genes were obtained. 35427441 7 55 theme transgene 1066:1074 arg1 absence 1044:1050 the absence 1040:1050 the absence of the SpCas9 transgene in T1 plants 1040:1087 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 4 56 theme fluorescent 617:627 arg1 marker 629:634 the DsRed2 fluorescent marker 606:634 the DsRed2 fluorescent marker for the identification and selection of transgenic plants 606:692 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants was established. 35427441 4 57 dep identification 644:657 arg1 the 640:642 the 640:642 the 640:642 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants was established. 35427441 1 58 mod modified 189:196 arg1 properties 129:138 The properties 125:138 The properties of host plants used for molecular farming 125:180 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 1 58 mod modified 189:196 arg3 editing 220:226 CRISPR/Cas9 genome editing 201:226 CRISPR/Cas9 genome editing 201:226 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 7 59 theme Leaf 994:997 arg1 fluorescence 999:1010 Leaf fluorescence 994:1010 Leaf fluorescence 994:1010 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 1 60 theme host 143:146 arg1 plants 148:153 host plants 143:153 host plants used for molecular farming 143:180 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 8 61 theme knockout 1339:1346 arg1 plants 1348:1353 the knockout plants 1335:1353 the knockout plants 1335:1353 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 35427441 7 62 theme T1 1079:1080 arg1 plants 1082:1087 T1 plants 1079:1087 T1 plants 1079:1087 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 6 63 theme transient 885:893 arg1 expression 895:904 transient expression 885:904 transient expression 885:904 Using preselected gRNAs with efficiencies confirmed by transient expression, transgenic plant lines with knockout mutations in all four NbP4H4 genes were obtained. 35427441 1 64 theme plants 148:153 arg1 properties 129:138 The properties 125:138 The properties of host plants used for molecular farming 125:180 The properties of host plants used for molecular farming can be modified by CRISPR/Cas9 genome editing to improve the quality and yield of recombinant proteins. 35427441 2 65 theme multiple 327:334 arg1 genes 336:340 multiple genes 327:340 multiple genes 327:340 However, it is often necessary to target multiple genes simultaneously, particularly when using host plants with large and complex genomes. 35427441 7 66 from transgene 1066:1074 arg1 plants 1082:1087 T1 plants 1079:1087 T1 plants 1079:1087 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 3 67 theme allotetraploid 473:486 arg1 relative 488:495 an allotetraploid relative 470:495 an allotetraploid relative of tobacco frequently used for transient protein expression 470:555 This is the case for Nicotiana benthamiana, an allotetraploid relative of tobacco frequently used for transient protein expression. 35427441 3 67 theme allotetraploid 473:486 arg1 benthamiana 457:467 Nicotiana benthamiana 447:467 Nicotiana benthamiana 447:467 This is the case for Nicotiana benthamiana, an allotetraploid relative of tobacco frequently used for transient protein expression. 35427441 7 68 from plants 1082:1087 arg1 absence 1044:1050 the absence 1040:1050 the absence of the SpCas9 transgene in T1 plants 1040:1087 Leaf fluorescence was then used to screen for the absence of the SpCas9 transgene in T1 plants, and transgene-free lines with homozygous or biallelic mutations were identified. 35427441 4 69 theme DsRed2 610:615 arg1 marker 629:634 the DsRed2 fluorescent marker 606:634 the DsRed2 fluorescent marker for the identification and selection of transgenic plants 606:692 A multiplex genome editing system incorporating the DsRed2 fluorescent marker for the identification and selection of transgenic plants was established. 35427441 2 70 with plants 387:392 arg1 genomes 417:423 large and complex genomes 399:423 large and complex genomes 399:423 However, it is often necessary to target multiple genes simultaneously, particularly when using host plants with large and complex genomes. 35427441 8 71 theme IgA1 1214:1217 arg1 analysis 1175:1182 The analysis 1171:1182 The analysis of plant-produced recombinant IgA1 as a reporter protein 1171:1239 The analysis of plant-produced recombinant IgA1 as a reporter protein revealed changes in the number of peptides containing hydroxyproline residues and pentoses in the knockout plants. 36912112 0 0 theme mammalian 94:102 arg1 cells 104:108 mammalian cells 94:108 mammalian cells 94:108 Characterization and expression of highly active recombinant human Glucuronyl C5-epimerase in mammalian cells. 36912112 0 1 from expression 21:30 arg1 cells 104:108 mammalian cells 94:108 mammalian cells 94:108 Characterization and expression of highly active recombinant human Glucuronyl C5-epimerase in mammalian cells. 36912112 10 2 theme active 1520:1525 arg1 HSepi 1527:1531 highly active HSepi 1513:1531 highly active HSepi 1513:1531 Together, this study contributes to the preparation of highly active HSepi for the enzymatic synthesis of heparins by providing additional insights into the catalytic activity of HSepi. 36912112 8 3 theme tyrosine 1163:1170 arg1 Tyr560 1214:1219 Tyr560 1214:1219 Tyr560 1214:1219 Further mutation studies suggest that tyrosine residues, such as Tyr168, Tyr222, Tyr500, Tyr560, and Tyr578, are crucial in maintaining HSepi activity. 36912112 8 3 theme tyrosine 1163:1170 arg1 Tyr578 1226:1231 Tyr578 1226:1231 Tyr578 1226:1231 Further mutation studies suggest that tyrosine residues, such as Tyr168, Tyr222, Tyr500, Tyr560, and Tyr578, are crucial in maintaining HSepi activity. 36912112 8 3 theme tyrosine 1163:1170 arg1 residues 1172:1179 tyrosine residues 1163:1179 tyrosine residues 1163:1179 Further mutation studies suggest that tyrosine residues, such as Tyr168, Tyr222, Tyr500, Tyr560, and Tyr578, are crucial in maintaining HSepi activity. 36912112 8 3 theme tyrosine 1163:1170 arg1 Tyr222 1198:1203 Tyr222 1198:1203 Tyr222 1198:1203 Further mutation studies suggest that tyrosine residues, such as Tyr168, Tyr222, Tyr500, Tyr560, and Tyr578, are crucial in maintaining HSepi activity. 36912112 8 3 theme tyrosine 1163:1170 arg1 Tyr500 1206:1211 Tyr500 1206:1211 Tyr500 1206:1211 Further mutation studies suggest that tyrosine residues, such as Tyr168, Tyr222, Tyr500, Tyr560, and Tyr578, are crucial in maintaining HSepi activity. 36912112 1 4 theme heparan 161:167 arg1 sulfate 169:175 heparan sulfate 161:175 heparan sulfate 161:175 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 7 5 theme post-translational 1028:1045 arg1 modifications 1047:1059 post-translational modifications 1028:1059 post-translational modifications 1028:1059 The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. 36912112 7 5 theme post-translational 1028:1045 arg1 formation 1114:1122 disulfide bond formation 1099:1122 disulfide bond formation 1099:1122 The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. 36912112 7 5 theme post-translational 1028:1045 arg1 glycosylation 1081:1093 N-linked glycosylation 1072:1093 N-linked glycosylation 1072:1093 The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. 36912112 4 6 theme polymerases 616:626 arg1 preparation 601:611 preparation 601:611 preparation 601:611 The synthesis of bioengineered heparin involves recombinant expression and preparation of polymerases, sulfotransferases, and an epimerase. 36912112 4 6 theme polymerases 616:626 arg1 expression 586:595 expression 586:595 expression 586:595 The synthesis of bioengineered heparin involves recombinant expression and preparation of polymerases, sulfotransferases, and an epimerase. 36912112 0 7 from Characterization 0:15 arg1 cells 104:108 mammalian cells 94:108 mammalian cells 94:108 Characterization and expression of highly active recombinant human Glucuronyl C5-epimerase in mammalian cells. 36912112 5 8 theme D-glucuronic 710:721 arg1 acids 723:727 D-glucuronic acids 710:727 D-glucuronic acids immediately adjacent to N-sulfo-glucosamine units to L-iduronic acid 710:796 D-glucuronyl C5-epimerase (HSepi) catalyzes D-glucuronic acids immediately adjacent to N-sulfo-glucosamine units to L-iduronic acid. 36912112 6 9 theme heparin 885:891 arg1 synthesis 893:901 in vitro heparin synthesis 876:901 in vitro heparin synthesis 876:901 Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis has not been resolved as of now. 36912112 8 10 theme mutation 1133:1140 arg1 studies 1142:1148 Further mutation studies 1125:1148 Further mutation studies 1125:1148 Further mutation studies suggest that tyrosine residues, such as Tyr168, Tyr222, Tyr500, Tyr560, and Tyr578, are crucial in maintaining HSepi activity. 36912112 9 11 theme recombinant 1384:1394 arg1 HSepi589 1403:1410 HSepi589 1403:1410 HSepi589 1403:1410 A high-yield expression strategy was established using the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg. 36912112 9 11 theme recombinant 1384:1394 arg1 HSepi 1396:1400 recombinant HSepi 1384:1400 recombinant HSepi (HSepi589) 1384:1411 A high-yield expression strategy was established using the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg. 36912112 7 12 theme bond 1109:1112 arg1 formation 1114:1122 disulfide bond formation 1099:1122 disulfide bond formation 1099:1122 The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. 36912112 9 13 theme up 1441:1442 arg1 activity 1429:1436 a specific activity 1418:1436 a specific activity of up to 1.6 IU/mg 1418:1455 A high-yield expression strategy was established using the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg. 36912112 4 14 theme sulfotransferases 629:645 arg1 preparation 601:611 preparation 601:611 preparation 601:611 The synthesis of bioengineered heparin involves recombinant expression and preparation of polymerases, sulfotransferases, and an epimerase. 36912112 4 14 theme sulfotransferases 629:645 arg1 expression 586:595 expression 586:595 expression 586:595 The synthesis of bioengineered heparin involves recombinant expression and preparation of polymerases, sulfotransferases, and an epimerase. 36912112 5 15 theme D-glucuronyl 666:677 arg1 HSepi 693:697 HSepi 693:697 HSepi 693:697 D-glucuronyl C5-epimerase (HSepi) catalyzes D-glucuronic acids immediately adjacent to N-sulfo-glucosamine units to L-iduronic acid. 36912112 5 15 theme D-glucuronyl 666:677 arg1 C5-epimerase 679:690 D-glucuronyl C5-epimerase 666:690 D-glucuronyl C5-epimerase (HSepi) 666:698 D-glucuronyl C5-epimerase (HSepi) catalyzes D-glucuronic acids immediately adjacent to N-sulfo-glucosamine units to L-iduronic acid. 36912112 6 16 theme in 876:877 arg1 synthesis 893:901 in vitro heparin synthesis 876:901 in vitro heparin synthesis 876:901 Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis has not been resolved as of now. 36912112 1 17 theme sulfate 169:175 arg1 form 153:156 a highly sulfated and epimerized form 120:156 a highly sulfated and epimerized form of heparan sulfate 120:175 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 1 17 theme sulfate 169:175 arg1 Heparin 111:117 Heparin 111:117 Heparin 111:117 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 8 18 theme Further 1125:1131 arg1 studies 1142:1148 Further mutation studies 1125:1148 Further mutation studies 1125:1148 Further mutation studies suggest that tyrosine residues, such as Tyr168, Tyr222, Tyr500, Tyr560, and Tyr578, are crucial in maintaining HSepi activity. 36912112 3 19 theme in 424:425 arg1 synthesis 443:451 The in vitro enzymatic synthesis 420:451 The in vitro enzymatic synthesis of heparin 420:462 The in vitro enzymatic synthesis of heparin has become a promising substitute for animal-derived heparin. 36912112 2 20 theme preparation 399:409 arg1 process 411:417 the preparation process 395:417 the preparation process 395:417 However, there are several noteworthy drawbacks associated with animal-sourced heparin during the preparation process. 36912112 3 21 dep in 424:425 arg1 vitro 427:431 vitro 427:431 vitro 427:431 The in vitro enzymatic synthesis of heparin has become a promising substitute for animal-derived heparin. 36912112 7 22 theme HSepi 1003:1007 arg1 activity 991:998 the catalytic activity 977:998 the catalytic activity of HSepi 977:1007 The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. 36912112 3 23 theme enzymatic 433:441 arg1 synthesis 443:451 The in vitro enzymatic synthesis 420:451 The in vitro enzymatic synthesis of heparin 420:462 The in vitro enzymatic synthesis of heparin has become a promising substitute for animal-derived heparin. 36912112 10 24 theme HSepi 1527:1531 arg1 preparation 1498:1508 the preparation 1494:1508 the preparation of highly active HSepi for the enzymatic synthesis of heparins 1494:1571 Together, this study contributes to the preparation of highly active HSepi for the enzymatic synthesis of heparins by providing additional insights into the catalytic activity of HSepi. 36912112 6 25 theme production 855:864 arg1 yield 866:870 production yield 855:870 production yield 855:870 Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis has not been resolved as of now. 36912112 10 26 theme enzymatic 1541:1549 arg1 synthesis 1551:1559 the enzymatic synthesis 1537:1559 the enzymatic synthesis of heparins 1537:1571 Together, this study contributes to the preparation of highly active HSepi for the enzymatic synthesis of heparins by providing additional insights into the catalytic activity of HSepi. 36912112 8 27 theme HSepi 1261:1265 arg1 activity 1267:1274 HSepi activity 1261:1274 HSepi activity 1261:1274 Further mutation studies suggest that tyrosine residues, such as Tyr168, Tyr222, Tyr500, Tyr560, and Tyr578, are crucial in maintaining HSepi activity. 36912112 7 28 theme catalytic 981:989 arg1 activity 991:998 the catalytic activity 977:998 the catalytic activity of HSepi 977:1007 The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. 36912112 9 29 theme high-yield 1279:1288 arg1 strategy 1301:1308 A high-yield expression strategy 1277:1308 A high-yield expression strategy 1277:1308 A high-yield expression strategy was established using the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg. 36912112 6 30 dep in 876:877 arg1 vitro 879:883 vitro 879:883 vitro 879:883 Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis has not been resolved as of now. 36912112 1 31 theme linear 183:188 arg1 polysaccharide 190:203 a linear polysaccharide 181:203 a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases 181:298 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 1 31 theme linear 183:188 arg1 Heparin 111:117 Heparin 111:117 Heparin 111:117 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 1 32 theme thrombotic 280:289 arg1 diseases 291:298 thrombotic diseases 280:298 thrombotic diseases 280:298 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 10 33 theme heparins 1564:1571 arg1 synthesis 1551:1559 the enzymatic synthesis 1537:1559 the enzymatic synthesis of heparins 1537:1571 Together, this study contributes to the preparation of highly active HSepi for the enzymatic synthesis of heparins by providing additional insights into the catalytic activity of HSepi. 36912112 9 34 theme expression 1290:1299 arg1 strategy 1301:1308 A high-yield expression strategy 1277:1308 A high-yield expression strategy 1277:1308 A high-yield expression strategy was established using the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg. 36912112 0 35 theme active 42:47 arg1 C5-epimerase 78:89 highly active recombinant human Glucuronyl C5-epimerase 35:89 highly active recombinant human Glucuronyl C5-epimerase 35:89 Characterization and expression of highly active recombinant human Glucuronyl C5-epimerase in mammalian cells. 36912112 7 36 link N-linked 1072:1079 arg1 glycosylation 1081:1093 N-linked glycosylation 1072:1093 N-linked glycosylation 1072:1093 The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. 36912112 5 37 theme L-iduronic 782:791 arg1 acid 793:796 L-iduronic acid 782:796 L-iduronic acid 782:796 D-glucuronyl C5-epimerase (HSepi) catalyzes D-glucuronic acids immediately adjacent to N-sulfo-glucosamine units to L-iduronic acid. 36912112 9 38 theme specific 1420:1427 arg1 activity 1429:1436 a specific activity 1418:1436 a specific activity of up to 1.6 IU/mg 1418:1455 A high-yield expression strategy was established using the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg. 36912112 4 39 theme heparin 557:563 arg1 synthesis 530:538 The synthesis 526:538 The synthesis of bioengineered heparin 526:563 The synthesis of bioengineered heparin involves recombinant expression and preparation of polymerases, sulfotransferases, and an epimerase. 36912112 1 40 with polysaccharide 190:203 arg1 activity 224:231 anticoagulant activity 210:231 anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases 210:298 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 7 41 theme disulfide 1099:1107 arg1 formation 1114:1122 disulfide bond formation 1099:1122 disulfide bond formation 1099:1122 The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. 36912112 1 42 theme anticoagulant 210:222 arg1 activity 224:231 anticoagulant activity 210:231 anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases 210:298 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 0 43 theme human 61:65 arg1 C5-epimerase 78:89 highly active recombinant human Glucuronyl C5-epimerase 35:89 highly active recombinant human Glucuronyl C5-epimerase 35:89 Characterization and expression of highly active recombinant human Glucuronyl C5-epimerase in mammalian cells. 36912112 4 44 theme bioengineered 543:555 arg1 heparin 557:563 bioengineered heparin 543:563 bioengineered heparin 543:563 The synthesis of bioengineered heparin involves recombinant expression and preparation of polymerases, sulfotransferases, and an epimerase. 36912112 6 45 with HSepi 826:830 arg1 yield 866:870 production yield 855:870 production yield 855:870 Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis has not been resolved as of now. 36912112 6 45 with HSepi 826:830 arg1 activity 842:849 high activity 837:849 high activity 837:849 Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis has not been resolved as of now. 36912112 6 46 theme high 837:840 arg1 activity 842:849 high activity 837:849 high activity 837:849 Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis has not been resolved as of now. 36912112 3 47 theme animal-derived 502:515 arg1 heparin 517:523 animal-derived heparin 502:523 animal-derived heparin 502:523 The in vitro enzymatic synthesis of heparin has become a promising substitute for animal-derived heparin. 36912112 0 48 theme recombinant 49:59 arg1 C5-epimerase 78:89 highly active recombinant human Glucuronyl C5-epimerase 35:89 highly active recombinant human Glucuronyl C5-epimerase 35:89 Characterization and expression of highly active recombinant human Glucuronyl C5-epimerase in mammalian cells. 36912112 4 49 theme recombinant 574:584 arg1 expression 586:595 expression 586:595 expression 586:595 The synthesis of bioengineered heparin involves recombinant expression and preparation of polymerases, sulfotransferases, and an epimerase. 36912112 5 50 theme adjacent 741:748 arg1 acids 723:727 D-glucuronic acids 710:727 D-glucuronic acids immediately adjacent to N-sulfo-glucosamine units to L-iduronic acid 710:796 D-glucuronyl C5-epimerase (HSepi) catalyzes D-glucuronic acids immediately adjacent to N-sulfo-glucosamine units to L-iduronic acid. 36912112 10 51 theme catalytic 1615:1623 arg1 activity 1625:1632 the catalytic activity 1611:1632 the catalytic activity of HSepi 1611:1641 Together, this study contributes to the preparation of highly active HSepi for the enzymatic synthesis of heparins by providing additional insights into the catalytic activity of HSepi. 36912112 10 52 theme HSepi 1637:1641 arg1 activity 1625:1632 the catalytic activity 1611:1632 the catalytic activity of HSepi 1611:1641 Together, this study contributes to the preparation of highly active HSepi for the enzymatic synthesis of heparins by providing additional insights into the catalytic activity of HSepi. 36912112 2 53 theme noteworthy 328:337 arg1 drawbacks 339:347 several noteworthy drawbacks 320:347 several noteworthy drawbacks associated with animal-sourced heparin during the preparation process 320:417 However, there are several noteworthy drawbacks associated with animal-sourced heparin during the preparation process. 36912112 3 54 link animal-derived 502:515 arg1 heparin 517:523 animal-derived heparin 502:523 animal-derived heparin 502:523 The in vitro enzymatic synthesis of heparin has become a promising substitute for animal-derived heparin. 36912112 6 55 theme HSepi 826:830 arg1 Preparation 799:809 Preparation 799:809 Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis 799:901 Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis has not been resolved as of now. 36912112 1 56 theme sulfated 129:136 arg1 form 153:156 a highly sulfated and epimerized form 120:156 a highly sulfated and epimerized form of heparan sulfate 120:175 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 1 56 theme sulfated 129:136 arg1 Heparin 111:117 Heparin 111:117 Heparin 111:117 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 5 57 theme N-sulfo-glucosamine 753:771 arg1 units 773:777 N-sulfo-glucosamine units 753:777 N-sulfo-glucosamine units to L-iduronic acid 753:796 D-glucuronyl C5-epimerase (HSepi) catalyzes D-glucuronic acids immediately adjacent to N-sulfo-glucosamine units to L-iduronic acid. 36912112 9 58 theme lentiviral-based 1336:1351 arg1 system 1366:1371 the lentiviral-based transduction system 1332:1371 the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg 1332:1455 A high-yield expression strategy was established using the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg. 36912112 6 59 theme recombinant 814:824 arg1 HSepi 826:830 recombinant HSepi 814:830 recombinant HSepi with high activity and production yield 814:870 Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis has not been resolved as of now. 36912112 10 60 theme additional 1586:1595 arg1 insights 1597:1604 additional insights 1586:1604 additional insights into the catalytic activity of HSepi 1586:1641 Together, this study contributes to the preparation of highly active HSepi for the enzymatic synthesis of heparins by providing additional insights into the catalytic activity of HSepi. 36912112 7 61 theme study 957:961 arg1 findings 940:947 The findings 936:947 The findings of this study 936:961 The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. 36912112 2 62 theme several 320:326 arg1 drawbacks 339:347 several noteworthy drawbacks 320:347 several noteworthy drawbacks associated with animal-sourced heparin during the preparation process 320:417 However, there are several noteworthy drawbacks associated with animal-sourced heparin during the preparation process. 36912112 0 63 theme C5-epimerase 78:89 arg1 expression 21:30 expression 21:30 expression 21:30 Characterization and expression of highly active recombinant human Glucuronyl C5-epimerase in mammalian cells. 36912112 0 63 theme C5-epimerase 78:89 arg1 Characterization 0:15 Characterization 0:15 Characterization 0:15 Characterization and expression of highly active recombinant human Glucuronyl C5-epimerase in mammalian cells. 36912112 9 64 theme transduction 1353:1364 arg1 system 1366:1371 the lentiviral-based transduction system 1332:1371 the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg 1332:1455 A high-yield expression strategy was established using the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg. 36912112 7 65 theme N-linked 1072:1079 arg1 glycosylation 1081:1093 N-linked glycosylation 1072:1093 N-linked glycosylation 1072:1093 The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. 36912112 1 66 theme epimerized 142:151 arg1 form 153:156 a highly sulfated and epimerized form 120:156 a highly sulfated and epimerized form of heparan sulfate 120:175 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 1 66 theme epimerized 142:151 arg1 Heparin 111:117 Heparin 111:117 Heparin 111:117 Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. 36912112 3 67 theme heparin 456:462 arg1 synthesis 443:451 The in vitro enzymatic synthesis 420:451 The in vitro enzymatic synthesis of heparin 420:462 The in vitro enzymatic synthesis of heparin has become a promising substitute for animal-derived heparin. 36912112 0 68 theme Glucuronyl 67:76 arg1 C5-epimerase 78:89 highly active recombinant human Glucuronyl C5-epimerase 35:89 highly active recombinant human Glucuronyl C5-epimerase 35:89 Characterization and expression of highly active recombinant human Glucuronyl C5-epimerase in mammalian cells. 36912112 3 69 dep promising 477:485 arg1 substitute 487:496 substitute 487:496 substitute for animal-derived heparin 487:523 The in vitro enzymatic synthesis of heparin has become a promising substitute for animal-derived heparin. 36912112 2 70 theme animal-sourced 365:378 arg1 heparin 380:386 animal-sourced heparin 365:386 animal-sourced heparin 365:386 However, there are several noteworthy drawbacks associated with animal-sourced heparin during the preparation process. 36912112 4 71 theme epimerase 655:663 arg1 preparation 601:611 preparation 601:611 preparation 601:611 The synthesis of bioengineered heparin involves recombinant expression and preparation of polymerases, sulfotransferases, and an epimerase. 36912112 4 71 theme epimerase 655:663 arg1 expression 586:595 expression 586:595 expression 586:595 The synthesis of bioengineered heparin involves recombinant expression and preparation of polymerases, sulfotransferases, and an epimerase. 36509773 3 0 theme organ-specific 333:346 arg1 tumor 348:352 the organ-specific tumor 329:352 the organ-specific tumor 329:352 Here, we demonstrate that the splicing events specifically active during human organogenesis, are broadly reactivated in the organ-specific tumor. 36509773 8 1 theme anti-cancer 1153:1163 arg1 targets 1165:1171 anti-cancer targets 1153:1171 anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators 1153:1257 Our study provides a comprehensive demonstration of a splicing-mediated link between development and cancer, and suggest anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators. 36509773 8 1 theme anti-cancer 1153:1163 arg1 events 1192:1197 splicing events 1183:1197 splicing events 1183:1197 Our study provides a comprehensive demonstration of a splicing-mediated link between development and cancer, and suggest anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators. 36509773 8 1 theme anti-cancer 1153:1163 arg1 splicing 1219:1226 their upstream splicing and transcriptional regulators 1204:1257 splicing 1219:1226 Our study provides a comprehensive demonstration of a splicing-mediated link between development and cancer, and suggest anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators. 36509773 5 2 theme coordinated 581:591 arg1 splicing 593:600 splicing 593:600 splicing 593:600 Such events preferentially target nitrosylation and transmembrane-region domains, whose coordinated splicing in multiple genes respectively affect intracellular transport and N-linked glycosylation. 36509773 6 3 theme critical 701:708 arg1 factors 719:725 critical splicing factors 701:725 critical splicing factors potentially regulating embryonic splicing events 701:774 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36509773 0 4 from misappropriation 6:21 arg1 organs 79:84 multiple organs 70:84 multiple organs 70:84 Broad misappropriation of developmental splicing profile by cancer in multiple organs. 36509773 3 5 theme splicing 238:245 arg1 events 247:252 the splicing events 234:252 the splicing events 234:252 Here, we demonstrate that the splicing events specifically active during human organogenesis, are broadly reactivated in the organ-specific tumor. 36509773 4 6 theme proliferation 423:435 arg1 rates 437:441 proliferation rates 423:441 proliferation rates in cancer cell lines as well as patient survival 423:490 Such events are associated with key oncogenic processes and predict proliferation rates in cancer cell lines as well as patient survival. 36509773 7 7 theme critical 986:993 arg1 factors 1004:1010 critical splicing factors 986:1010 critical splicing factors in brain and liver 986:1029 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 5 8 theme N-linked 668:675 arg1 glycosylation 677:689 N-linked glycosylation 668:689 N-linked glycosylation 668:689 Such events preferentially target nitrosylation and transmembrane-region domains, whose coordinated splicing in multiple genes respectively affect intracellular transport and N-linked glycosylation. 36509773 6 9 theme potential 807:815 arg1 drivers 827:833 potential oncogenic drivers 807:833 potential oncogenic drivers 807:833 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36509773 6 9 theme potential 807:815 arg1 factors 795:801 such factors 790:801 such factors 790:801 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36509773 2 10 theme underlying 157:166 arg1 mechanisms 168:177 the underlying mechanisms 153:177 the underlying mechanisms 153:177 However, the underlying mechanisms are incompletely understood. 36509773 4 11 from rates 437:441 arg1 lines 458:462 cancer cell lines 446:462 cancer cell lines as well as patient survival 446:490 Such events are associated with key oncogenic processes and predict proliferation rates in cancer cell lines as well as patient survival. 36509773 4 11 from rates 437:441 arg1 survival 483:490 patient survival 475:490 cancer cell lines as well as patient survival 446:490 Such events are associated with key oncogenic processes and predict proliferation rates in cancer cell lines as well as patient survival. 36509773 8 12 theme link 1104:1107 arg1 demonstration 1067:1079 a comprehensive demonstration 1051:1079 a comprehensive demonstration of a splicing-mediated link between development and cancer 1051:1138 Our study provides a comprehensive demonstration of a splicing-mediated link between development and cancer, and suggest anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators. 36509773 5 13 link N-linked 668:675 arg1 glycosylation 677:689 N-linked glycosylation 668:689 N-linked glycosylation 668:689 Such events preferentially target nitrosylation and transmembrane-region domains, whose coordinated splicing in multiple genes respectively affect intracellular transport and N-linked glycosylation. 36509773 7 14 from factors 1004:1010 arg1 liver 1025:1029 liver 1025:1029 liver 1025:1029 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 7 14 from factors 1004:1010 arg1 brain 1015:1019 brain 1015:1019 brain 1015:1019 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 5 15 theme nitrosylation 527:539 arg1 domains 566:572 nitrosylation and transmembrane-region domains 527:572 nitrosylation and transmembrane-region domains 527:572 Such events preferentially target nitrosylation and transmembrane-region domains, whose coordinated splicing in multiple genes respectively affect intracellular transport and N-linked glycosylation. 36509773 0 16 theme profile 49:55 arg1 misappropriation 6:21 Broad misappropriation 0:21 Broad misappropriation of developmental splicing profile by cancer in multiple organs 0:84 Broad misappropriation of developmental splicing profile by cancer in multiple organs. 36509773 4 17 theme oncogenic 391:399 arg1 processes 401:409 key oncogenic processes 387:409 key oncogenic processes 387:409 Such events are associated with key oncogenic processes and predict proliferation rates in cancer cell lines as well as patient survival. 36509773 6 18 theme such 790:793 arg1 drivers 827:833 potential oncogenic drivers 807:833 potential oncogenic drivers 807:833 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36509773 6 18 theme such 790:793 arg1 factors 795:801 such factors 790:801 such factors 790:801 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36509773 4 19 theme key 387:389 arg1 processes 401:409 key oncogenic processes 387:409 key oncogenic processes 387:409 Such events are associated with key oncogenic processes and predict proliferation rates in cancer cell lines as well as patient survival. 36509773 7 20 from brain 1015:1019 arg1 regulators 972:981 potential transcriptional regulators 946:981 potential transcriptional regulators of critical splicing factors in brain and liver 946:1029 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 5 21 theme transmembrane-region 545:564 arg1 domains 566:572 nitrosylation and transmembrane-region domains 527:572 nitrosylation and transmembrane-region domains 527:572 Such events preferentially target nitrosylation and transmembrane-region domains, whose coordinated splicing in multiple genes respectively affect intracellular transport and N-linked glycosylation. 36509773 0 22 theme Broad 0:4 arg1 misappropriation 6:21 Broad misappropriation 0:21 Broad misappropriation of developmental splicing profile by cancer in multiple organs 0:84 Broad misappropriation of developmental splicing profile by cancer in multiple organs. 36509773 5 23 theme intracellular 640:652 arg1 transport 654:662 intracellular transport 640:662 intracellular transport 640:662 Such events preferentially target nitrosylation and transmembrane-region domains, whose coordinated splicing in multiple genes respectively affect intracellular transport and N-linked glycosylation. 36509773 7 24 theme transcriptional 956:970 arg1 regulators 972:981 potential transcriptional regulators 946:981 potential transcriptional regulators of critical splicing factors in brain and liver 946:1029 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 0 25 theme developmental 26:38 arg1 profile 49:55 developmental splicing profile 26:55 developmental splicing profile 26:55 Broad misappropriation of developmental splicing profile by cancer in multiple organs. 36509773 8 26 theme upstream 1210:1217 arg1 splicing 1219:1226 their upstream splicing and transcriptional regulators 1204:1257 splicing 1219:1226 Our study provides a comprehensive demonstration of a splicing-mediated link between development and cancer, and suggest anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators. 36509773 6 27 theme malignant 871:879 arg1 cells 881:885 malignant cells 871:885 malignant cells 871:885 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36509773 1 28 theme key 106:108 arg1 aspects 110:116 key aspects 106:116 key aspects of embryonic development 106:141 Oncogenesis mimics key aspects of embryonic development. 36509773 5 29 theme Such 493:496 arg1 events 498:503 Such events 493:503 Such events 493:503 Such events preferentially target nitrosylation and transmembrane-region domains, whose coordinated splicing in multiple genes respectively affect intracellular transport and N-linked glycosylation. 36509773 8 30 theme comprehensive 1053:1065 arg1 demonstration 1067:1079 a comprehensive demonstration 1051:1079 a comprehensive demonstration of a splicing-mediated link between development and cancer 1051:1138 Our study provides a comprehensive demonstration of a splicing-mediated link between development and cancer, and suggest anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators. 36509773 7 31 theme complementary 897:909 arg1 analyses 911:918 Multiple complementary analyses 888:918 Multiple complementary analyses 888:918 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 3 32 dep events 247:252 arg1 active 267:272 active 267:272 active 267:272 Here, we demonstrate that the splicing events specifically active during human organogenesis, are broadly reactivated in the organ-specific tumor. 36509773 3 33 theme human 281:285 arg1 organogenesis 287:299 human organogenesis 281:299 human organogenesis 281:299 Here, we demonstrate that the splicing events specifically active during human organogenesis, are broadly reactivated in the organ-specific tumor. 36509773 6 34 theme splicing 760:767 arg1 events 769:774 embryonic splicing events 750:774 embryonic splicing events 750:774 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36509773 5 35 from splicing 593:600 arg1 genes 614:618 multiple genes 605:618 multiple genes 605:618 Such events preferentially target nitrosylation and transmembrane-region domains, whose coordinated splicing in multiple genes respectively affect intracellular transport and N-linked glycosylation. 36509773 0 36 theme splicing 40:47 arg1 profile 49:55 developmental splicing profile 26:55 developmental splicing profile 26:55 Broad misappropriation of developmental splicing profile by cancer in multiple organs. 36509773 7 37 theme Multiple 888:895 arg1 analyses 911:918 Multiple complementary analyses 888:918 Multiple complementary analyses 888:918 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 4 38 theme patient 475:481 arg1 survival 483:490 patient survival 475:490 cancer cell lines as well as patient survival 446:490 Such events are associated with key oncogenic processes and predict proliferation rates in cancer cell lines as well as patient survival. 36509773 8 39 theme transcriptional 1232:1246 arg1 regulators 1248:1257 their upstream splicing and transcriptional regulators 1204:1257 regulators 1248:1257 Our study provides a comprehensive demonstration of a splicing-mediated link between development and cancer, and suggest anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators. 36509773 4 40 theme cell 453:456 arg1 lines 458:462 cancer cell lines 446:462 cancer cell lines as well as patient survival 446:490 Such events are associated with key oncogenic processes and predict proliferation rates in cancer cell lines as well as patient survival. 36509773 8 41 theme splicing 1183:1190 arg1 events 1192:1197 splicing events 1183:1197 splicing events 1183:1197 Our study provides a comprehensive demonstration of a splicing-mediated link between development and cancer, and suggest anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators. 36509773 5 42 theme multiple 605:612 arg1 genes 614:618 multiple genes 605:618 multiple genes 605:618 Such events preferentially target nitrosylation and transmembrane-region domains, whose coordinated splicing in multiple genes respectively affect intracellular transport and N-linked glycosylation. 36509773 1 43 theme embryonic 121:129 arg1 development 131:141 embryonic development 121:141 embryonic development 121:141 Oncogenesis mimics key aspects of embryonic development. 36509773 6 44 theme embryonic 750:758 arg1 events 769:774 embryonic splicing events 750:774 embryonic splicing events 750:774 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36509773 4 45 theme cancer 446:451 arg1 lines 458:462 cancer cell lines 446:462 cancer cell lines as well as patient survival 446:490 Such events are associated with key oncogenic processes and predict proliferation rates in cancer cell lines as well as patient survival. 36509773 8 46 theme splicing-mediated 1086:1102 arg1 link 1104:1107 a splicing-mediated link 1084:1107 a splicing-mediated link between development and cancer 1084:1138 Our study provides a comprehensive demonstration of a splicing-mediated link between development and cancer, and suggest anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators. 36509773 1 47 theme development 131:141 arg1 aspects 110:116 key aspects 106:116 key aspects of embryonic development 106:141 Oncogenesis mimics key aspects of embryonic development. 36509773 6 48 theme oncogenic 817:825 arg1 drivers 827:833 potential oncogenic drivers 807:833 potential oncogenic drivers 807:833 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36509773 6 48 theme oncogenic 817:825 arg1 factors 795:801 such factors 790:801 such factors 790:801 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36509773 7 49 from liver 1025:1029 arg1 regulators 972:981 potential transcriptional regulators 946:981 potential transcriptional regulators of critical splicing factors in brain and liver 946:1029 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 7 50 theme potential 946:954 arg1 regulators 972:981 potential transcriptional regulators 946:981 potential transcriptional regulators of critical splicing factors in brain and liver 946:1029 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 0 51 theme multiple 70:77 arg1 organs 79:84 multiple organs 70:84 multiple organs 70:84 Broad misappropriation of developmental splicing profile by cancer in multiple organs. 36509773 7 52 theme splicing 995:1002 arg1 factors 1004:1010 critical splicing factors 986:1010 critical splicing factors in brain and liver 986:1029 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 7 53 from regulators 972:981 arg1 liver 1025:1029 liver 1025:1029 liver 1025:1029 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 7 53 from regulators 972:981 arg1 brain 1015:1019 brain 1015:1019 brain 1015:1019 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 7 54 theme factors 1004:1010 arg1 regulators 972:981 potential transcriptional regulators 946:981 potential transcriptional regulators of critical splicing factors in brain and liver 946:1029 Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. 36509773 4 55 theme Such 355:358 arg1 events 360:365 Such events 355:365 Such events 355:365 Such events are associated with key oncogenic processes and predict proliferation rates in cancer cell lines as well as patient survival. 36509773 6 56 theme splicing 710:717 arg1 factors 719:725 critical splicing factors 701:725 critical splicing factors potentially regulating embryonic splicing events 701:774 We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. 36452458 1 0 theme self-replicating 293:308 arg1 state 310:314 a disease-associated self-replicating state 272:314 a disease-associated self-replicating state 272:314 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 6 1 theme ST6Gal1 1233:1239 arg1 mice 1250:1253 ST6Gal1 knockout mice 1233:1253 ST6Gal1 knockout mice 1233:1253 However, the sialylation of PrPSc remained stable and the incubation time to disease increased only modestly in ST6Gal1 knockout mice (ST6Gal1-KO). 36452458 1 2 theme Prion 125:129 arg1 group 146:150 a group 144:150 a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 144:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 1 2 theme Prion 125:129 arg1 diseases 179:186 fatal neurodegenerative diseases 155:186 fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 155:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 1 2 theme Prion 125:129 arg1 diseases 131:138 Prion diseases 125:138 Prion diseases 125:138 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 3 3 theme prions 683:688 arg1 fate 675:678 the fate 671:678 the fate of prions in an organism 671:703 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 1 4 theme normal 216:221 arg1 form 232:235 the normal cellular form 212:235 the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 212:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 4 5 theme disease 922:928 arg1 pathogenesis 930:941 prion disease pathogenesis 916:941 prion disease pathogenesis 916:941 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 3 6 theme replication 646:656 arg1 rate 632:635 the rate 628:635 the rate of prion replication 628:656 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 1 7 theme cellular 223:230 arg1 form 232:235 the normal cellular form 212:235 the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 212:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 0 8 theme minor 74:78 arg1 effect 80:85 only a minor effect 67:85 only a minor effect 67:85 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 0 9 from Deficiency 0:9 arg1 ST6GAL1 14:20 ST6GAL1 14:20 ST6GAL1 14:20 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 0 9 from Deficiency 0:9 arg1 α2,6-sialyltransferases 38:60 the two α2,6-sialyltransferases 30:60 the two α2,6-sialyltransferases 30:60 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 0 9 from Deficiency 0:9 arg1 one 23:25 one 23:25 one 23:25 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 6 10 theme PrPSc 1149:1153 arg1 sialylation 1134:1144 the sialylation 1130:1144 the sialylation of PrPSc 1130:1153 However, the sialylation of PrPSc remained stable and the incubation time to disease increased only modestly in ST6Gal1 knockout mice (ST6Gal1-KO). 36452458 7 11 from redundancy 1375:1384 arg1 sialylation 1389:1399 sialylation 1389:1399 sialylation 1389:1399 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 1 12 theme form 232:235 arg1 misfolding 198:207 misfolding 198:207 misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 198:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 6 13 dep increased 1206:1214 arg1 ST6Gal1-KO 1256:1265 ST6Gal1-KO 1256:1265 ST6Gal1-KO 1256:1265 However, the sialylation of PrPSc remained stable and the incubation time to disease increased only modestly in ST6Gal1 knockout mice (ST6Gal1-KO). 36452458 1 14 theme PrPSc 319:323 arg1 form 232:235 the normal cellular form 212:235 the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 212:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 4 15 theme current 710:716 arg1 study 718:722 The current study 706:722 The current study 706:722 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 7 16 from lack 1271:1274 arg1 status 1324:1329 the PrPSc sialylation status 1302:1329 the PrPSc sialylation status 1302:1329 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 7 16 from lack 1271:1274 arg1 pathogenesis 1341:1352 prion pathogenesis 1335:1352 prion pathogenesis 1335:1352 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 4 17 gly sialylation 877:887 arg1 PrPSc 899:903 PrPSc 899:903 PrPSc 899:903 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 4 18 theme mammalian 776:784 arg1 sialyltransferases 786:803 the two mammalian sialyltransferases 768:803 the two mammalian sialyltransferases 768:803 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 2 19 dep acids 448:452 arg1 residues 454:461 residues 454:461 sialic acids residues 441:461 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 4 20 theme PrPSc 899:903 arg1 status 889:894 the sialylation status 873:894 the sialylation status of PrPSc 873:903 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 5 21 theme brain 1045:1049 arg1 parenchyma 1051:1060 the brain parenchyma 1041:1060 the brain parenchyma 1041:1060 We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. 36452458 7 22 theme family 1491:1496 arg1 member 1459:1464 a second member 1450:1464 a second member of the sialyltransferase family that sialylate via α2-6 linkages 1450:1529 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 7 22 theme family 1491:1496 arg1 ST6Gal2 1532:1538 ST6Gal2 1532:1538 ST6Gal2 1532:1538 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 7 23 theme changes 1291:1297 arg1 lack 1271:1274 A lack 1269:1274 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis 1269:1352 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 2 24 theme terminal 410:417 arg1 positions 419:427 the terminal positions 406:427 the terminal positions occupied by sialic acids residues 406:461 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 5 25 theme parenchyma 1051:1060 arg1 sialylation 1026:1036 the α2-6 sialylation 1017:1036 the α2-6 sialylation of the brain parenchyma 1017:1060 We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. 36452458 5 26 from mice 990:993 arg1 knockout 967:974 knockout 967:974 knockout 967:974 We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. 36452458 7 27 theme prion 1335:1339 arg1 pathogenesis 1341:1352 prion pathogenesis 1335:1352 prion pathogenesis 1335:1352 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 2 28 mod modified 365:372 arg1 PrPSc 335:339 PrPSc 335:339 PrPSc 335:339 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 2 28 mod modified 365:372 arg1 PrPC 326:329 PrPC 326:329 PrPC 326:329 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 2 28 mod modified 365:372 arg3 glycans 388:394 N-linked glycans 379:394 N-linked glycans 379:394 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 4 29 gly sialylation 823:833 arg1 glycans 838:844 glycans 838:844 glycans 838:844 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 4 30 theme sialylation 877:887 arg1 status 889:894 the sialylation status 873:894 the sialylation status of PrPSc 873:903 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 4 31 theme sialyltransferases 786:803 arg1 sialyltransferases 786:803 the two mammalian sialyltransferases 768:803 the two mammalian sialyltransferases 768:803 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 4 31 theme sialyltransferases 786:803 arg1 one 761:763 one 761:763 one 761:763 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 4 31 theme sialyltransferases 786:803 arg1 knockout 740:747 knockout 740:747 knockout 740:747 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 3 32 theme PrPSc 548:552 arg1 status 538:543 The sialylation status 522:543 The sialylation status of PrPSc 522:552 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 3 32 theme PrPSc 548:552 arg1 determinant 570:580 an important determinant 557:580 an important determinant of prion disease pathogenesis 557:610 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 5 33 from knockout 967:974 arg1 mice 990:993 mice 990:993 mice 990:993 We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. 36452458 1 34 theme prion 244:248 arg1 PrPC 261:264 the prion protein or PrPC 240:264 the prion protein or PrPC 240:264 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 7 35 theme sialyltransferase 1473:1489 arg1 family 1491:1496 the sialyltransferase family 1469:1496 the sialyltransferase family 1469:1496 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 3 36 theme sialylation 526:536 arg1 status 538:543 The sialylation status 522:543 The sialylation status of PrPSc 522:552 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 3 36 theme sialylation 526:536 arg1 determinant 570:580 an important determinant 557:580 an important determinant of prion disease pathogenesis 557:610 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 7 37 theme PrPSc 1306:1310 arg1 status 1324:1329 the PrPSc sialylation status 1302:1329 the PrPSc sialylation status 1302:1329 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 1 38 theme fatal 155:159 arg1 diseases 179:186 fatal neurodegenerative diseases 155:186 fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 155:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 5 39 theme ST6Gal1 979:985 arg1 knockout 967:974 knockout 967:974 knockout 967:974 We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. 36452458 1 40 theme protein 250:256 arg1 PrPC 261:264 the prion protein or PrPC 240:264 the prion protein or PrPC 240:264 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 7 41 theme member 1459:1464 arg1 involvement 1435:1445 the plausible involvement 1421:1445 the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2 1421:1538 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 1 42 theme neurodegenerative 161:177 arg1 diseases 179:186 fatal neurodegenerative diseases 155:186 fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 155:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 2 43 theme sialic 441:446 arg1 acids 448:452 sialic acids 441:452 sialic acids residues 441:461 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 1 44 theme or 258:259 arg1 PrPC 261:264 the prion protein or PrPC 240:264 the prion protein or PrPC 240:264 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 0 45 theme prion 110:114 arg1 disease 116:122 prion disease 110:122 prion disease 110:122 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 2 46 theme N-linked 379:386 arg1 glycans 388:394 N-linked glycans 379:394 N-linked glycans 379:394 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 3 47 theme important 560:568 arg1 status 538:543 The sialylation status 522:543 The sialylation status of PrPSc 522:552 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 3 47 theme important 560:568 arg1 determinant 570:580 an important determinant 557:580 an important determinant of prion disease pathogenesis 557:610 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 1 48 theme diseases 179:186 arg1 group 146:150 a group 144:150 a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 144:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 1 48 theme diseases 179:186 arg1 diseases 179:186 fatal neurodegenerative diseases 155:186 fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 155:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 1 48 theme diseases 179:186 arg1 diseases 131:138 Prion diseases 125:138 Prion diseases 125:138 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 1 49 theme PrPC 261:264 arg1 form 232:235 the normal cellular form 212:235 the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc 212:323 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 2 50 theme α2-6 507:510 arg1 linkages 512:519 α2-6 linkages 507:519 α2-6 linkages 507:519 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 5 51 theme α2-6 1021:1024 arg1 sialylation 1026:1036 the α2-6 sialylation 1017:1036 the α2-6 sialylation of the brain parenchyma 1017:1060 We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. 36452458 7 52 theme sialylation 1312:1322 arg1 status 1324:1329 the PrPSc sialylation status 1302:1329 the PrPSc sialylation status 1302:1329 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 7 53 from changes 1291:1297 arg1 status 1324:1329 the PrPSc sialylation status 1302:1329 the PrPSc sialylation status 1302:1329 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 7 53 from changes 1291:1297 arg1 pathogenesis 1341:1352 prion pathogenesis 1335:1352 prion pathogenesis 1335:1352 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 7 54 theme significant 1279:1289 arg1 changes 1291:1297 significant changes 1279:1297 significant changes in the PrPSc sialylation status and prion pathogenesis 1279:1352 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 7 55 theme second 1452:1457 arg1 member 1459:1464 a second member 1450:1464 a second member of the sialyltransferase family that sialylate via α2-6 linkages 1450:1529 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 7 55 theme second 1452:1457 arg1 ST6Gal2 1532:1538 ST6Gal2 1532:1538 ST6Gal2 1532:1538 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 6 56 theme incubation 1179:1188 arg1 time 1190:1193 the incubation time 1175:1193 the incubation time to disease 1175:1204 However, the sialylation of PrPSc remained stable and the incubation time to disease increased only modestly in ST6Gal1 knockout mice (ST6Gal1-KO). 36452458 5 57 theme Sambucus 1094:1101 arg1 agglutinin 1109:1118 Sambucus Nigra agglutinin 1094:1118 Sambucus Nigra agglutinin 1094:1118 We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. 36452458 0 58 theme disease 116:122 arg1 pathogenesis 94:105 the pathogenesis 90:105 the pathogenesis of prion disease 90:122 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 2 59 link N-linked 379:386 arg1 glycans 388:394 N-linked glycans 379:394 N-linked glycans 379:394 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 7 60 from status 1324:1329 arg1 lack 1271:1274 A lack 1269:1274 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis 1269:1352 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 5 61 theme Nigra 1103:1107 arg1 agglutinin 1109:1118 Sambucus Nigra agglutinin 1094:1118 Sambucus Nigra agglutinin 1094:1118 We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. 36452458 6 62 theme knockout 1241:1248 arg1 mice 1250:1253 ST6Gal1 knockout mice 1233:1253 ST6Gal1 knockout mice 1233:1253 However, the sialylation of PrPSc remained stable and the incubation time to disease increased only modestly in ST6Gal1 knockout mice (ST6Gal1-KO). 36452458 3 63 theme prion 640:644 arg1 replication 646:656 prion replication 640:656 prion replication 640:656 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 3 64 theme disease 591:597 arg1 pathogenesis 599:610 prion disease pathogenesis 585:610 prion disease pathogenesis 585:610 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 6 65 gly sialylation 1134:1144 arg1 PrPSc 1149:1153 PrPSc 1149:1153 PrPSc 1149:1153 However, the sialylation of PrPSc remained stable and the incubation time to disease increased only modestly in ST6Gal1 knockout mice (ST6Gal1-KO). 36452458 7 66 theme α2-6 1517:1520 arg1 linkages 1522:1529 α2-6 linkages 1517:1529 α2-6 linkages 1517:1529 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 4 67 theme α2-6 850:853 arg1 linkages 855:862 α2-6 linkages 850:862 α2-6 linkages 850:862 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 3 68 theme pathogenesis 599:610 arg1 status 538:543 The sialylation status 522:543 The sialylation status of PrPSc 522:552 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 3 68 theme pathogenesis 599:610 arg1 determinant 570:580 an important determinant 557:580 an important determinant of prion disease pathogenesis 557:610 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 0 69 contain has 63:65 arg1 Deficiency 0:9 Deficiency 0:9 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, 0:61 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 0 69 contain has 63:65 arg2 effect 80:85 only a minor effect 67:85 only a minor effect 67:85 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 3 70 gly sialylation 526:536 arg1 PrPSc 548:552 PrPSc 548:552 PrPSc 548:552 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 5 71 gly sialylation 1026:1036 arg1 parenchyma 1051:1060 the brain parenchyma 1041:1060 the brain parenchyma 1041:1060 We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. 36452458 4 72 theme prion 916:920 arg1 pathogenesis 930:941 prion disease pathogenesis 916:941 prion disease pathogenesis 916:941 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 7 73 theme plausible 1425:1433 arg1 involvement 1435:1445 the plausible involvement 1421:1445 the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2 1421:1538 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 4 74 theme ST6Gal1 752:758 arg1 sialyltransferases 786:803 the two mammalian sialyltransferases 768:803 the two mammalian sialyltransferases 768:803 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 4 74 theme ST6Gal1 752:758 arg1 one 761:763 one 761:763 one 761:763 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 4 74 theme ST6Gal1 752:758 arg1 knockout 740:747 knockout 740:747 knockout 740:747 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 2 75 attach attached 467:474 arg1 galactose 479:487 galactose 479:487 galactose 479:487 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 2 75 attach attached 467:474 arg2 positions 419:427 the terminal positions 406:427 the terminal positions occupied by sialic acids residues 406:461 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 2 75 attach attached 467:474 arg3 glycans 388:394 N-linked glycans 379:394 N-linked glycans 379:394 PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. 36452458 4 76 theme glycans 838:844 arg1 sialylation 823:833 the sialylation 819:833 the sialylation of glycans 819:844 The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. 36452458 7 77 from pathogenesis 1341:1352 arg1 lack 1271:1274 A lack 1269:1274 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis 1269:1352 A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. 36452458 0 78 theme α2,6-sialyltransferases 38:60 arg1 ST6GAL1 14:20 ST6GAL1 14:20 ST6GAL1 14:20 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 0 78 theme α2,6-sialyltransferases 38:60 arg1 α2,6-sialyltransferases 38:60 the two α2,6-sialyltransferases 30:60 the two α2,6-sialyltransferases 30:60 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 0 78 theme α2,6-sialyltransferases 38:60 arg1 one 23:25 one 23:25 one 23:25 Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease. 36452458 1 79 theme disease-associated 274:291 arg1 state 310:314 a disease-associated self-replicating state 272:314 a disease-associated self-replicating state 272:314 Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. 36452458 3 80 theme prion 585:589 arg1 pathogenesis 599:610 prion disease pathogenesis 585:610 prion disease pathogenesis 585:610 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36452458 3 81 from fate 675:678 arg1 organism 696:703 an organism 693:703 an organism 693:703 The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. 36722968 11 0 from heterodimers 2014:2025 arg1 surface 2048:2054 the parasite cell surface 2030:2054 the parasite cell surface 2030:2054 Our studies identify a family of glycoproteins that form heterodimers on the parasite cell surface to facilitate host cell attachment and entry. 36722968 10 1 theme stages 1915:1920 arg1 end 1899:1901 the apical end 1888:1901 the apical end of invasive stages called sporozoites and merozoites 1888:1954 To expand our understanding of this process, we characterized the antigens recognized by a monoclonal antibody that stains the apical end of invasive stages called sporozoites and merozoites. 36722968 10 2 theme invasive 1906:1913 arg1 stages 1915:1920 invasive stages 1906:1920 invasive stages called sporozoites and merozoites 1906:1954 To expand our understanding of this process, we characterized the antigens recognized by a monoclonal antibody that stains the apical end of invasive stages called sporozoites and merozoites. 36722968 2 3 theme host 345:348 arg1 cell 350:353 host cell attachment and invasion 345:377 host cell attachment and invasion 345:377 Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. 36722968 1 4 theme unique 244:249 arg1 location 263:270 a unique epicellular location 242:270 a unique epicellular location 242:270 Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. 36722968 3 5 theme cell 547:550 arg1 attachment 552:561 cell attachment 547:561 cell attachment 547:561 The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. 36722968 4 6 theme antibody 659:666 arg1 1A5 674:676 monoclonal antibody (MAb) 1A5 648:676 monoclonal antibody (MAb) 1A5 648:676 Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. 36722968 6 7 gly glycoproteins 967:979 arg1 glycoproteins 967:979 Paralogous glycoproteins 956:979 Paralogous glycoproteins recognized by MAb 1A5 956:1001 Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. 36722968 2 8 theme apicomplexan 304:315 arg1 parasites 317:325 related apicomplexan parasites 296:325 related apicomplexan parasites 296:325 Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. 36722968 7 9 contain contains 1289:1296 arg1 partner 1274:1280 its partner 1270:1280 its partner 1270:1280 Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. 36722968 7 9 contain contains 1289:1296 arg2 domain 1311:1316 a mucin-like domain 1298:1316 a mucin-like domain related to GP900 1298:1333 Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. 36722968 11 10 theme cell 2043:2046 arg1 surface 2048:2054 the parasite cell surface 2030:2054 the parasite cell surface 2030:2054 Our studies identify a family of glycoproteins that form heterodimers on the parasite cell surface to facilitate host cell attachment and entry. 36722968 8 11 theme host 1425:1428 arg1 attachment 1435:1444 host cell attachment 1425:1444 host cell attachment 1425:1444 Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. 36722968 12 12 gly glycoproteins 2145:2157 arg1 glycoproteins 2145:2157 mucin-like glycoproteins 2134:2157 mucin-like glycoproteins 2134:2157 By further defining the role of mucin-like glycoproteins in host cell attachment, our studies may lead to strategies to disrupt cell adhesion and thereby decrease infection. 36722968 5 13 theme paralogous 846:855 arg1 proteins 857:864 paralogous proteins 846:864 paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species 846:953 Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. 36722968 9 14 theme cell 1727:1730 arg1 attachment 1732:1741 cell attachment 1727:1741 cell attachment 1727:1741 IMPORTANCE Although Cryptosporidium is extremely efficient at penetrating mucus and invading epithelial cells in the intestine, the mechanism of cell attachment is poorly understood. 36722968 6 15 contain contain 1125:1131 arg2 oligosaccharides 1154:1169 mucin-like, O-linked oligosaccharides 1133:1169 oligosaccharides 1154:1169 Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. 36722968 6 15 contain contain 1125:1131 arg1 they 1120:1123 they 1120:1123 they 1120:1123 Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. 36722968 10 16 theme process 1801:1807 arg1 understanding 1779:1791 our understanding 1775:1791 our understanding of this process 1775:1807 To expand our understanding of this process, we characterized the antigens recognized by a monoclonal antibody that stains the apical end of invasive stages called sporozoites and merozoites. 36722968 5 17 with Immunoprecipitation 745:763 arg1 1A5 774:776 MAb 1A5 770:776 MAb 1A5 770:776 Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. 36722968 1 18 theme Cryptosporidium 106:120 arg1 pathogen 143:150 an enteric pathogen 132:150 an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location 132:270 Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. 36722968 1 18 theme Cryptosporidium 106:120 arg1 parvum 122:127 Cryptosporidium parvum 106:127 Cryptosporidium parvum 106:127 Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. 36722968 5 19 theme additional 887:896 arg1 orthologs 898:906 additional orthologs 887:906 additional orthologs in the genome of C. parvum and related species 887:953 Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. 36722968 5 20 from orthologs 898:906 arg1 genome 915:920 the genome 911:920 the genome of C. parvum and related species 911:953 Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. 36722968 8 21 theme new 1486:1488 arg1 family 1490:1495 a new family 1484:1495 a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp 1484:1579 Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. 36722968 2 22 dep cell 350:353 arg1 invasion 370:377 invasion 370:377 invasion 370:377 Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. 36722968 2 22 dep cell 350:353 arg1 attachment 355:364 attachment 355:364 attachment 355:364 Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. 36722968 7 23 theme mucin-like 1300:1309 arg1 domain 1311:1316 a mucin-like domain 1298:1316 a mucin-like domain related to GP900 1298:1333 Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. 36722968 3 24 theme C. 431:432 arg1 genome 441:446 The streamlined C. parvum genome 415:446 The streamlined C. parvum genome 415:446 The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. 36722968 12 25 from role 2126:2129 arg1 attachment 2172:2181 host cell attachment 2162:2181 host cell attachment 2162:2181 By further defining the role of mucin-like glycoproteins in host cell attachment, our studies may lead to strategies to disrupt cell adhesion and thereby decrease infection. 36722968 8 26 theme glycoproteins 1510:1522 arg1 family 1490:1495 a new family 1484:1495 a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp 1484:1579 Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. 36722968 4 27 theme sporozoites 710:720 arg1 end 703:705 the apical end 692:705 the apical end of sporozoites and mature merozoites 692:742 Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. 36722968 0 28 theme Apical 0:5 arg1 Glycoprotein 17:28 Apical Secretory Glycoprotein 0:28 Apical Secretory Glycoprotein Complex 0:36 Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum. 36722968 7 29 theme related 1318:1324 arg1 domain 1311:1316 a mucin-like domain 1298:1316 a mucin-like domain related to GP900 1298:1333 Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. 36722968 11 30 gly glycoproteins 1990:2002 arg1 glycoproteins 1990:2002 glycoproteins 1990:2002 glycoproteins that form heterodimers on the parasite cell surface to facilitate host cell attachment and entry 1990:2099 Our studies identify a family of glycoproteins that form heterodimers on the parasite cell surface to facilitate host cell attachment and entry. 36722968 4 31 theme mature 726:731 arg1 merozoites 733:742 mature merozoites 726:742 mature merozoites 726:742 Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. 36722968 3 32 theme numerous 457:464 arg1 glycoproteins 477:489 numerous mucin-like glycoproteins 457:489 numerous mucin-like glycoproteins 457:489 The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. 36722968 0 33 theme Glycoprotein 17:28 arg1 Complex 30:36 Apical Secretory Glycoprotein Complex 0:36 Apical Secretory Glycoprotein Complex 0:36 Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum. 36722968 5 34 theme species 947:953 arg1 genome 915:920 the genome 911:920 the genome of C. parvum and related species 911:953 Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. 36722968 6 35 theme parasite 1048:1055 arg1 surface 1057:1063 the parasite surface 1044:1063 the parasite surface 1044:1063 Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. 36722968 8 36 theme cell 1544:1547 arg1 invasion 1549:1556 cell invasion 1544:1556 cell invasion by Cryptosporidium spp 1544:1579 Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. 36722968 12 37 theme mucin-like 2134:2143 arg1 glycoproteins 2145:2157 mucin-like glycoproteins 2134:2157 mucin-like glycoproteins 2134:2157 By further defining the role of mucin-like glycoproteins in host cell attachment, our studies may lead to strategies to disrupt cell adhesion and thereby decrease infection. 36722968 0 38 dep Cell 53:56 arg1 Entry 73:77 Entry 73:77 Entry 73:77 Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum. 36722968 0 38 dep Cell 53:56 arg1 Attachment 58:67 Attachment 58:67 Attachment 58:67 Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum. 36722968 8 39 theme MAb 1393:1395 arg1 1A5 1397:1399 MAb 1A5 1393:1399 MAb 1A5 1393:1399 Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. 36722968 10 40 theme apical 1892:1897 arg1 end 1899:1901 the apical end 1888:1901 the apical end of invasive stages called sporozoites and merozoites 1888:1954 To expand our understanding of this process, we characterized the antigens recognized by a monoclonal antibody that stains the apical end of invasive stages called sporozoites and merozoites. 36722968 12 41 theme cell 2167:2170 arg1 attachment 2172:2181 host cell attachment 2162:2181 host cell attachment 2162:2181 By further defining the role of mucin-like glycoproteins in host cell attachment, our studies may lead to strategies to disrupt cell adhesion and thereby decrease infection. 36722968 3 42 theme glycoproteins 477:489 arg1 several 492:498 several 492:498 several 492:498 The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. 36722968 11 43 dep cell 2075:2078 arg1 entry 2095:2099 entry 2095:2099 entry 2095:2099 Our studies identify a family of glycoproteins that form heterodimers on the parasite cell surface to facilitate host cell attachment and entry. 36722968 11 43 dep cell 2075:2078 arg1 attachment 2080:2089 attachment 2080:2089 attachment 2080:2089 Our studies identify a family of glycoproteins that form heterodimers on the parasite cell surface to facilitate host cell attachment and entry. 36722968 7 44 theme paralogs 1210:1217 arg1 one 1199:1201 one 1199:1201 one 1199:1201 Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. 36722968 7 44 theme paralogs 1210:1217 arg1 paralogs 1210:1217 the paralogs 1206:1217 the paralogs 1206:1217 Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. 36722968 2 45 theme cell 350:353 arg1 processes 332:340 the processes 328:340 the processes of host cell attachment and invasion by C. parvum 328:390 Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. 36722968 7 46 theme CRISPR/Cas9 1244:1254 arg1 editing 1261:1267 CRISPR/Cas9 gene editing 1244:1267 CRISPR/Cas9 gene editing 1244:1267 Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. 36722968 1 47 theme epicellular 251:261 arg1 location 263:270 a unique epicellular location 242:270 a unique epicellular location 242:270 Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. 36722968 9 48 theme epithelial 1675:1684 arg1 cells 1686:1690 epithelial cells 1675:1690 epithelial cells in the intestine 1675:1707 IMPORTANCE Although Cryptosporidium is extremely efficient at penetrating mucus and invading epithelial cells in the intestine, the mechanism of cell attachment is poorly understood. 36722968 8 49 gly glycoproteins 1510:1522 arg1 glycoproteins 1510:1522 secretory glycoproteins 1500:1522 secretory glycoproteins that participate in cell invasion by Cryptosporidium spp 1500:1579 Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. 36722968 4 50 theme monoclonal 648:657 arg1 antibody 659:666 monoclonal antibody 648:666 monoclonal antibody (MAb) 1A5 648:676 Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. 36722968 4 50 theme monoclonal 648:657 arg1 MAb 669:671 MAb 669:671 MAb 669:671 Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. 36722968 6 51 theme O-linked 1145:1152 arg1 oligosaccharides 1154:1169 mucin-like, O-linked oligosaccharides 1133:1169 oligosaccharides 1154:1169 Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. 36722968 12 52 theme glycoproteins 2145:2157 arg1 role 2126:2129 the role 2122:2129 the role of mucin-like glycoproteins in host cell attachment 2122:2181 By further defining the role of mucin-like glycoproteins in host cell attachment, our studies may lead to strategies to disrupt cell adhesion and thereby decrease infection. 36722968 2 53 theme related 296:302 arg1 parasites 317:325 related apicomplexan parasites 296:325 related apicomplexan parasites 296:325 Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. 36722968 6 54 theme Paralogous 956:965 arg1 glycoproteins 967:979 Paralogous glycoproteins 956:979 Paralogous glycoproteins recognized by MAb 1A5 956:1001 Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. 36722968 3 55 contain contains 448:455 arg2 glycoproteins 477:489 numerous mucin-like glycoproteins 457:489 numerous mucin-like glycoproteins 457:489 The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. 36722968 3 55 contain contains 448:455 arg1 genome 441:446 The streamlined C. parvum genome 415:446 The streamlined C. parvum genome 415:446 The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. 36722968 6 56 theme mucin-like 1133:1142 arg1 oligosaccharides 1154:1169 mucin-like, O-linked oligosaccharides 1133:1169 oligosaccharides 1154:1169 Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. 36722968 11 57 theme host 2070:2073 arg1 cell 2075:2078 host cell attachment and entry 2070:2099 host cell attachment and entry 2070:2099 Our studies identify a family of glycoproteins that form heterodimers on the parasite cell surface to facilitate host cell attachment and entry. 36722968 9 58 theme attachment 1732:1741 arg1 mechanism 1714:1722 the mechanism 1710:1722 the mechanism of cell attachment 1710:1741 IMPORTANCE Although Cryptosporidium is extremely efficient at penetrating mucus and invading epithelial cells in the intestine, the mechanism of cell attachment is poorly understood. 36722968 11 59 theme glycoproteins 1990:2002 arg1 family 1980:1985 a family 1978:1985 a family of glycoproteins that form heterodimers on the parasite cell surface to facilitate host cell attachment and entry 1978:2099 Our studies identify a family of glycoproteins that form heterodimers on the parasite cell surface to facilitate host cell attachment and entry. 36722968 1 60 theme enteric 135:141 arg1 pathogen 143:150 an enteric pathogen 132:150 an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location 132:270 Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. 36722968 1 60 theme enteric 135:141 arg1 parvum 122:127 Cryptosporidium parvum 106:127 Cryptosporidium parvum 106:127 Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. 36722968 11 61 theme parasite 2034:2041 arg1 surface 2048:2054 the parasite cell surface 2030:2054 the parasite cell surface 2030:2054 Our studies identify a family of glycoproteins that form heterodimers on the parasite cell surface to facilitate host cell attachment and entry. 36722968 4 62 theme apical 696:701 arg1 end 703:705 the apical end 692:705 the apical end of sporozoites and mature merozoites 692:742 Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. 36722968 0 63 theme Cryptosporidium 82:96 arg1 parvum 98:103 Cryptosporidium parvum 82:103 Cryptosporidium parvum 82:103 Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum. 36722968 9 64 from cells 1686:1690 arg1 intestine 1699:1707 the intestine 1695:1707 the intestine 1695:1707 IMPORTANCE Although Cryptosporidium is extremely efficient at penetrating mucus and invading epithelial cells in the intestine, the mechanism of cell attachment is poorly understood. 36722968 1 65 theme epithelial 165:174 arg1 cells 176:180 epithelial cells 165:180 epithelial cells 165:180 Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. 36722968 8 66 theme cell 1430:1433 arg1 attachment 1435:1444 host cell attachment 1425:1444 host cell attachment 1425:1444 Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. 36722968 8 67 theme 1A5 1397:1399 arg1 ability 1382:1388 the ability 1378:1388 the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites 1378:1459 Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. 36722968 6 68 theme MAb 995:997 arg1 1A5 999:1001 MAb 1A5 995:1001 MAb 1A5 995:1001 Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. 36722968 8 69 theme secretory 1500:1508 arg1 glycoproteins 1510:1522 secretory glycoproteins 1500:1522 secretory glycoproteins that participate in cell invasion by Cryptosporidium spp 1500:1579 Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. 36722968 12 70 theme cell 2230:2233 arg1 adhesion 2235:2242 cell adhesion 2230:2242 cell adhesion 2230:2242 By further defining the role of mucin-like glycoproteins in host cell attachment, our studies may lead to strategies to disrupt cell adhesion and thereby decrease infection. 36722968 4 71 theme merozoites 733:742 arg1 end 703:705 the apical end 692:705 the apical end of sporozoites and mature merozoites 692:742 Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. 36722968 6 72 link O-linked 1145:1152 arg1 oligosaccharides 1154:1169 mucin-like, O-linked oligosaccharides 1133:1169 oligosaccharides 1154:1169 Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. 36722968 2 73 theme C. 382:383 arg1 parvum 385:390 C. parvum 382:390 C. parvum 382:390 Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. 36722968 0 74 theme Secretory 7:15 arg1 Glycoprotein 17:28 Apical Secretory Glycoprotein 0:28 Apical Secretory Glycoprotein Complex 0:36 Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum. 36722968 5 75 theme parvum 928:933 arg1 genome 915:920 the genome 911:920 the genome of C. parvum and related species 911:953 Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. 36722968 3 76 theme streamlined 419:429 arg1 genome 441:446 The streamlined C. parvum genome 415:446 The streamlined C. parvum genome 415:446 The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. 36722968 5 77 theme related 939:945 arg1 species 947:953 related species 939:953 related species 939:953 Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. 36722968 3 78 gly glycoproteins 477:489 arg1 glycoproteins 477:489 numerous mucin-like glycoproteins 457:489 numerous mucin-like glycoproteins 457:489 The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. 36722968 3 79 theme mucin-like 466:475 arg1 glycoproteins 477:489 numerous mucin-like glycoproteins 457:489 numerous mucin-like glycoproteins 457:489 The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. 36722968 5 80 theme MAb 770:772 arg1 1A5 774:776 MAb 1A5 770:776 MAb 1A5 770:776 Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. 36722968 8 81 theme Cryptosporidium 1561:1575 arg1 spp 1577:1579 Cryptosporidium spp 1561:1579 Cryptosporidium spp 1561:1579 Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp. 36722968 10 82 theme monoclonal 1856:1865 arg1 antibody 1867:1874 a monoclonal antibody 1854:1874 a monoclonal antibody that stains the apical end of invasive stages called sporozoites and merozoites 1854:1954 To expand our understanding of this process, we characterized the antigens recognized by a monoclonal antibody that stains the apical end of invasive stages called sporozoites and merozoites. 36722968 12 83 theme host 2162:2165 arg1 attachment 2172:2181 host cell attachment 2162:2181 host cell attachment 2162:2181 By further defining the role of mucin-like glycoproteins in host cell attachment, our studies may lead to strategies to disrupt cell adhesion and thereby decrease infection. 36722968 1 84 theme apical 224:229 arg1 surface 231:237 the apical surface 220:237 the apical surface 220:237 Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. 36722968 7 85 theme gene 1256:1259 arg1 editing 1261:1267 CRISPR/Cas9 gene editing 1244:1267 CRISPR/Cas9 gene editing 1244:1267 Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. 36722968 3 86 theme parvum 434:439 arg1 genome 441:446 The streamlined C. parvum genome 415:446 The streamlined C. parvum genome 415:446 The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. 36722968 5 87 theme mass 790:793 arg1 spectrometry 795:806 mass spectrometry 790:806 mass spectrometry 790:806 Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. 36721988 8 0 from THBS1 1199:1203 arg1 secretion 1172:1180 secretion 1172:1180 secretion of TSRs 1-3 from THBS1 1172:1203 Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1. 36721988 11 1 dep suggested 1673:1681 arg1 Combined 1650:1657 Combined 1650:1657 Combined 1650:1657 Combined these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from loss of the glucose-fucose disaccharide. 36721988 7 2 theme TSR 989:991 arg1 domains 993:999 TSR domains 989:999 TSR domains 989:999 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 7 3 theme endoplasmic 904:914 arg1 reticulum 916:924 the endoplasmic reticulum 900:924 the endoplasmic reticulum 900:924 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 1 4 theme processes 256:264 arg1 processes 256:264 cellular and physiological processes 229:264 cellular and physiological processes 229:264 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 1 4 theme processes 256:264 arg1 variety 218:224 a variety 216:224 a variety of cellular and physiological processes 216:264 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 7 5 theme substrates 1084:1093 arg1 secretion 1052:1060 proper secretion 1045:1060 proper secretion of many O-fucosylated substrates 1045:1093 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 9 6 from B3glct 1380:1385 arg1 mice 1390:1393 mice 1390:1393 mice 1390:1393 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 3 7 theme O-linked 499:506 arg1 disaccharide 523:534 O-linked glucose-fucose disaccharide 499:534 O-linked glucose-fucose disaccharide 499:534 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 9 8 theme major 1480:1484 arg1 granules 1455:1462 secretory granules 1445:1462 secretory granules of platelets 1445:1475 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 9 8 theme major 1480:1484 arg1 source 1486:1491 a major source 1478:1491 a major source of THBS1 1478:1500 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 8 9 from knockdown 1127:1135 arg1 cells 1158:1162 HEK293T cells 1150:1162 HEK293T cells 1150:1162 Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1. 36721988 0 10 theme platelet 99:106 arg1 granules 118:125 platelet secretory granules 99:125 platelet secretory granules 99:125 O-fucosylation of thrombospondin type I repeats is dispensable for trafficking thrombospondin 1 to platelet secretory granules. 36721988 9 11 from Pofut2 1370:1375 arg1 mice 1390:1393 mice 1390:1393 mice 1390:1393 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 1 12 gly glycoprotein 188:199 arg1 glycoprotein 188:199 a secreted extracellular matrix glycoprotein 156:199 a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes 156:264 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 1 12 gly glycoprotein 188:199 arg1 Thrombospondin 128:141 Thrombospondin 1 128:143 Thrombospondin 1 (THBS1) 128:151 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 11 13 mod modified 1730:1737 arg3 C-mannose 1742:1750 C-mannose 1742:1750 C-mannose 1742:1750 Combined these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from loss of the glucose-fucose disaccharide. 36721988 11 13 mod modified 1730:1737 arg1 TSRs 1711:1714 TSRs 1711:1714 TSRs that are also modified by C-mannose 1711:1750 Combined these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from loss of the glucose-fucose disaccharide. 36721988 10 14 theme platelet 1558:1565 arg1 THBS1 1567:1571 platelet THBS1 1558:1571 platelet THBS1 1558:1571 Additionally, we demonstrated that all three TSRs from platelet THBS1 were highly C-mannosylated, which has been shown to stabilize TSRs in vitro. 36721988 9 15 theme POFUT2 1312:1317 arg1 knockout 1300:1307 knockout 1300:1307 knockout 1300:1307 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 5 16 theme Protein 671:677 arg1 O-fucosyltransferase 679:698 Protein O-fucosyltransferase 2 671:700 Protein O-fucosyltransferase 2 (POFUT2) 671:709 The O-fucose is added by Protein O-fucosyltransferase 2 (POFUT2) and is sequentially extended to the disaccharide by β3glucosyltransferase (B3GLCT). 36721988 5 16 theme Protein 671:677 arg1 POFUT2 703:708 POFUT2 703:708 POFUT2 703:708 The O-fucose is added by Protein O-fucosyltransferase 2 (POFUT2) and is sequentially extended to the disaccharide by β3glucosyltransferase (B3GLCT). 36721988 8 17 theme siRNA 1121:1125 arg1 knockdown 1127:1135 the siRNA knockdown 1117:1135 the siRNA knockdown of POFUT2 in HEK293T cells 1117:1162 Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1. 36721988 11 18 with substrates 1695:1704 arg1 TSRs 1711:1714 TSRs 1711:1714 TSRs that are also modified by C-mannose 1711:1750 Combined these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from loss of the glucose-fucose disaccharide. 36721988 9 19 theme THBS1 1496:1500 arg1 granules 1455:1462 secretory granules 1445:1462 secretory granules of platelets 1445:1475 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 9 19 theme THBS1 1496:1500 arg1 source 1486:1491 a major source 1478:1491 a major source of THBS1 1478:1500 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 8 20 theme TSRs 1185:1188 arg1 secretion 1172:1180 secretion 1172:1180 secretion of TSRs 1-3 from THBS1 1172:1203 Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1. 36721988 7 21 gly O-fucosylation 865:878 arg1 reticulum 916:924 the endoplasmic reticulum 900:924 the endoplasmic reticulum 900:924 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 7 22 theme quality 962:968 arg1 control 970:976 quality control 962:976 quality control 962:976 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 9 23 theme endogenous 1425:1434 arg1 THBS1 1436:1440 endogenous THBS1 1425:1440 endogenous THBS1 1425:1440 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 9 24 theme secretory 1445:1453 arg1 granules 1455:1462 secretory granules 1445:1462 secretory granules of platelets 1445:1475 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 9 24 theme secretory 1445:1453 arg1 source 1486:1491 a major source 1478:1491 a major source of THBS1 1478:1500 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 1 25 theme secreted 158:165 arg1 glycoprotein 188:199 a secreted extracellular matrix glycoprotein 156:199 a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes 156:264 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 1 25 theme secreted 158:165 arg1 Thrombospondin 128:141 Thrombospondin 1 128:143 Thrombospondin 1 (THBS1) 128:151 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 0 26 theme secretory 108:116 arg1 granules 118:125 platelet secretory granules 99:125 platelet secretory granules 99:125 O-fucosylation of thrombospondin type I repeats is dispensable for trafficking thrombospondin 1 to platelet secretory granules. 36721988 9 27 theme HEK293T 1322:1328 arg1 cells 1330:1334 HEK293T cells 1322:1334 HEK293T cells 1322:1334 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 2 28 with interactions 311:322 arg1 array 369:373 an array 366:373 an array of proteins found in the extracellular matrix 366:419 THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. 36721988 6 29 theme C-mannosyltransferases 841:862 arg1 C-mannosyltransferases 841:862 four C-mannosyltransferases 836:862 four C-mannosyltransferases 836:862 The C-mannose is added by one or more of four C-mannosyltransferases. 36721988 6 29 theme C-mannosyltransferases 841:862 arg1 one 821:823 one 821:823 one 821:823 The C-mannose is added by one or more of four C-mannosyltransferases. 36721988 2 30 theme diverse 275:281 arg1 functions 283:291 THBS1's diverse functions 267:291 THBS1's diverse functions 267:291 THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. 36721988 1 31 theme extracellular 167:179 arg1 glycoprotein 188:199 a secreted extracellular matrix glycoprotein 156:199 a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes 156:264 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 1 31 theme extracellular 167:179 arg1 Thrombospondin 128:141 Thrombospondin 1 128:143 Thrombospondin 1 (THBS1) 128:151 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 8 32 theme HEK293T 1150:1156 arg1 cells 1158:1162 HEK293T cells 1150:1162 HEK293T cells 1150:1162 Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1. 36721988 1 33 theme matrix 181:186 arg1 glycoprotein 188:199 a secreted extracellular matrix glycoprotein 156:199 a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes 156:264 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 1 33 theme matrix 181:186 arg1 Thrombospondin 128:141 Thrombospondin 1 128:143 Thrombospondin 1 (THBS1) 128:151 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 11 34 theme trafficking 1779:1789 arg1 defects 1791:1797 trafficking defects 1779:1797 trafficking defects resulting from loss of the glucose-fucose disaccharide 1779:1852 Combined these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from loss of the glucose-fucose disaccharide. 36721988 3 35 dep THBS1 422:426 arg1 Repeats 458:464 three Thrombospondin Type 1 Repeats 430:464 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains 422:479 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 3 35 dep THBS1 422:426 arg1 TSRs 467:470 TSRs 467:470 TSRs 467:470 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 2 36 theme proteins 378:385 arg1 array 369:373 an array 366:373 an array of proteins found in the extracellular matrix 366:419 THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. 36721988 0 37 theme type 33:36 arg1 repeats 40:46 thrombospondin type I repeats 18:46 thrombospondin type I repeats 18:46 O-fucosylation of thrombospondin type I repeats is dispensable for trafficking thrombospondin 1 to platelet secretory granules. 36721988 7 38 theme O-fucosylated 1070:1082 arg1 substrates 1084:1093 many O-fucosylated substrates 1065:1093 many O-fucosylated substrates 1065:1093 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 9 39 theme THBS1 1436:1440 arg1 trafficking 1410:1420 trafficking 1410:1420 trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1 1410:1500 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 11 40 theme glucose-fucose 1826:1839 arg1 disaccharide 1841:1852 the glucose-fucose disaccharide 1822:1852 the glucose-fucose disaccharide 1822:1852 Combined these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from loss of the glucose-fucose disaccharide. 36721988 0 41 theme thrombospondin 18:31 arg1 repeats 40:46 thrombospondin type I repeats 18:46 thrombospondin type I repeats 18:46 O-fucosylation of thrombospondin type I repeats is dispensable for trafficking thrombospondin 1 to platelet secretory granules. 36721988 3 42 link O-linked 499:506 arg1 disaccharide 523:534 O-linked glucose-fucose disaccharide 499:534 O-linked glucose-fucose disaccharide 499:534 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 9 43 theme TSRs 1251:1254 arg1 secretion 1232:1240 secretion 1232:1240 secretion of THBS1 TSRs 1-3 1232:1258 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 9 44 theme platelets 1467:1475 arg1 granules 1455:1462 secretory granules 1445:1462 secretory granules of platelets 1445:1475 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 9 44 theme platelets 1467:1475 arg1 source 1486:1491 a major source 1478:1491 a major source of THBS1 1478:1500 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 0 45 theme repeats 40:46 arg1 O-fucosylation 0:13 O-fucosylation 0:13 O-fucosylation of thrombospondin type I repeats 0:46 O-fucosylation of thrombospondin type I repeats is dispensable for trafficking thrombospondin 1 to platelet secretory granules. 36721988 11 46 theme disaccharide 1841:1852 arg1 loss 1814:1817 loss 1814:1817 loss of the glucose-fucose disaccharide 1814:1852 Combined these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from loss of the glucose-fucose disaccharide. 36721988 11 47 theme POFUT2 1688:1693 arg1 substrates 1695:1704 POFUT2 substrates 1688:1704 POFUT2 substrates with TSRs that are also modified by C-mannose 1688:1750 Combined these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from loss of the glucose-fucose disaccharide. 36721988 0 48 gly O-fucosylation 0:13 arg1 repeats 40:46 thrombospondin type I repeats 18:46 thrombospondin type I repeats 18:46 O-fucosylation of thrombospondin type I repeats is dispensable for trafficking thrombospondin 1 to platelet secretory granules. 36721988 3 49 mod modified 485:492 arg3 disaccharide 523:534 O-linked glucose-fucose disaccharide 499:534 O-linked glucose-fucose disaccharide 499:534 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 3 49 mod modified 485:492 arg3 C-mannose 540:548 C-mannose 540:548 C-mannose 540:548 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 3 49 mod modified 485:492 arg1 domains 473:479 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains 422:479 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains 422:479 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 3 50 theme THBS1 422:426 arg1 domains 473:479 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains 422:479 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains 422:479 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 7 51 theme many 1065:1068 arg1 substrates 1084:1093 many O-fucosylated substrates 1065:1093 many O-fucosylated substrates 1065:1093 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 9 52 theme THBS1 1245:1249 arg1 TSRs 1251:1254 THBS1 TSRs 1-3 1245:1258 THBS1 TSRs 1-3 1245:1258 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 2 53 theme extracellular 400:412 arg1 matrix 414:419 the extracellular matrix 396:419 the extracellular matrix 396:419 THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. 36721988 8 54 dep showed 1110:1115 arg1 blocked 1164:1170 blocked 1164:1170 showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1 1110:1203 Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1. 36721988 9 55 theme Pofut2 1370:1375 arg1 knockout 1358:1365 knockout 1358:1365 knockout 1358:1365 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 7 56 theme proper 1045:1050 arg1 secretion 1052:1060 proper secretion 1045:1060 proper secretion of many O-fucosylated substrates 1045:1093 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 3 57 theme Thrombospondin 436:449 arg1 Type 451:454 Thrombospondin Type 1 436:456 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains 422:479 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 2 58 theme THBS1 355:359 arg1 THBS1 355:359 THBS1 355:359 THBS1 355:359 THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. 36721988 2 58 theme THBS1 355:359 arg1 domains 344:350 the modular domains 332:350 the modular domains of THBS1 332:359 THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. 36721988 8 59 theme Prior 1096:1100 arg1 studies 1102:1108 Prior studies 1096:1108 Prior studies 1096:1108 Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1. 36721988 9 60 theme B3glct 1380:1385 arg1 knockout 1358:1365 knockout 1358:1365 knockout 1358:1365 Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. 36721988 10 61 gly C-mannosylated 1585:1598 arg1 TSRs 1548:1551 all three TSRs 1538:1551 all three TSRs from platelet THBS1 1538:1571 Additionally, we demonstrated that all three TSRs from platelet THBS1 were highly C-mannosylated, which has been shown to stabilize TSRs in vitro. 36721988 7 62 theme 3-dimensional 1012:1024 arg1 fold 1026:1029 their 3-dimensional fold 1006:1029 their 3-dimensional fold 1006:1029 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 10 63 from THBS1 1567:1571 arg1 TSRs 1548:1551 all three TSRs 1538:1551 all three TSRs from platelet THBS1 1538:1571 Additionally, we demonstrated that all three TSRs from platelet THBS1 were highly C-mannosylated, which has been shown to stabilize TSRs in vitro. 36721988 2 64 theme modular 336:342 arg1 THBS1 355:359 THBS1 355:359 THBS1 355:359 THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. 36721988 2 64 theme modular 336:342 arg1 domains 344:350 the modular domains 332:350 the modular domains of THBS1 332:359 THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. 36721988 1 65 theme cellular 229:236 arg1 processes 256:264 cellular and physiological processes 229:264 cellular and physiological processes 229:264 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36721988 0 66 theme trafficking 67:77 arg1 thrombospondin 79:92 trafficking thrombospondin 1 67:94 trafficking thrombospondin 1 to platelet secretory granules 67:125 O-fucosylation of thrombospondin type I repeats is dispensable for trafficking thrombospondin 1 to platelet secretory granules. 36721988 2 67 located found 387:391 arg1 matrix 414:419 the extracellular matrix 396:419 the extracellular matrix 396:419 THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. 36721988 2 67 located found 387:391 arg2 proteins 378:385 proteins 378:385 proteins found in the extracellular matrix 378:419 THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. 36721988 7 68 from O-fucosylation 865:878 arg1 reticulum 916:924 the endoplasmic reticulum 900:924 the endoplasmic reticulum 900:924 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 3 69 theme glucose-fucose 508:521 arg1 disaccharide 523:534 O-linked glucose-fucose disaccharide 499:534 O-linked glucose-fucose disaccharide 499:534 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 3 70 theme Type 451:454 arg1 Repeats 458:464 three Thrombospondin Type 1 Repeats 430:464 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains 422:479 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 3 70 theme Type 451:454 arg1 TSRs 467:470 TSRs 467:470 TSRs 467:470 THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. 36721988 8 71 theme POFUT2 1140:1145 arg1 knockdown 1127:1135 the siRNA knockdown 1117:1135 the siRNA knockdown of POFUT2 in HEK293T cells 1117:1162 Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1. 36721988 4 72 theme THBS1 631:635 arg1 trafficking 600:610 trafficking 600:610 trafficking 600:610 It is unknown whether these modifications impact trafficking and/or function of THBS1 in vivo. 36721988 7 73 gly O-fucosylated 1070:1082 arg1 substrates 1084:1093 many O-fucosylated substrates 1065:1093 many O-fucosylated substrates 1065:1093 O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. 36721988 1 74 theme physiological 242:254 arg1 processes 256:264 cellular and physiological processes 229:264 cellular and physiological processes 229:264 Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. 36495345 4 0 theme HCC 495:497 arg1 patients 499:506 HCC patients 495:506 HCC patients 495:506 We found that b3galt5 is highly expressed and associated with a poor prognosis in HCC patients. 36495345 4 1 theme poor 477:480 arg1 prognosis 482:490 a poor prognosis 475:490 a poor prognosis in HCC patients 475:506 We found that b3galt5 is highly expressed and associated with a poor prognosis in HCC patients. 36495345 8 2 theme mTOR/p70s6k 849:859 arg1 pathway 861:867 the mTOR/p70s6k pathway 845:867 the mTOR/p70s6k pathway 845:867 Mechanistically, b3galt5 promoted glycolysis by activating the mTOR/p70s6k pathway through O-linked glycosylation modification on mTOR. 36495345 9 3 theme glycolysis 1007:1016 arg1 rate 1018:1021 the glycolysis rate 1003:1021 the glycolysis rate in b3galt5-overexpressing cells 1003:1053 Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. 36495345 10 4 theme b3galt5-mTOR/p70s6k 1156:1174 arg1 axis 1176:1179 the b3galt5-mTOR/p70s6k axis 1152:1179 the b3galt5-mTOR/p70s6k axis 1152:1179 Our study uncovers a novel mechanism by which b3galt5 mediates glycolysis in HCC and highlights the b3galt5-mTOR/p70s6k axis as a potential target for HCC therapy. 36495345 10 4 theme b3galt5-mTOR/p70s6k 1156:1174 arg1 target 1196:1201 a potential target 1184:1201 a potential target for HCC therapy 1184:1217 Our study uncovers a novel mechanism by which b3galt5 mediates glycolysis in HCC and highlights the b3galt5-mTOR/p70s6k axis as a potential target for HCC therapy. 36495345 5 5 theme cells 593:597 arg1 survival 577:584 survival 577:584 survival 577:584 In vitro studies showed that b3galt5 promoted the proliferation and survival of HCC cells. 36495345 5 5 theme cells 593:597 arg1 proliferation 559:571 proliferation 559:571 proliferation 559:571 In vitro studies showed that b3galt5 promoted the proliferation and survival of HCC cells. 36495345 1 6 theme high 178:181 arg1 morbidity 183:191 morbidity 183:191 morbidity 183:191 Hepatocellular carcinoma (HCC) is one of the most common malignancies with high morbidity and mortality. 36495345 7 7 theme aerobic 759:765 arg1 glycolysis 767:776 aerobic glycolysis 759:776 aerobic glycolysis 759:776 Further investigation confirmed that b3galt5 promoted aerobic glycolysis in HCC. 36495345 3 8 theme underlying 373:382 arg1 mechanism 384:392 underlying mechanism 373:392 underlying mechanism 373:392 Here, we investigated the role and underlying mechanism of b3galt5 in HCC. 36495345 3 9 from mechanism 384:392 arg1 HCC 408:410 HCC 408:410 HCC 408:410 Here, we investigated the role and underlying mechanism of b3galt5 in HCC. 36495345 1 10 with malignancies 160:171 arg1 mortality 197:205 mortality 197:205 mortality 197:205 Hepatocellular carcinoma (HCC) is one of the most common malignancies with high morbidity and mortality. 36495345 1 10 with malignancies 160:171 arg1 morbidity 183:191 morbidity 183:191 morbidity 183:191 Hepatocellular carcinoma (HCC) is one of the most common malignancies with high morbidity and mortality. 36495345 8 11 from modification 900:911 arg1 mTOR 916:919 mTOR 916:919 mTOR 916:919 Mechanistically, b3galt5 promoted glycolysis by activating the mTOR/p70s6k pathway through O-linked glycosylation modification on mTOR. 36495345 9 12 theme b3galt5-overexpressing 1026:1047 arg1 cells 1049:1053 b3galt5-overexpressing cells 1026:1053 b3galt5-overexpressing cells 1026:1053 Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. 36495345 6 13 theme b3galt5 626:632 arg1 deficiency 634:643 b3galt5 deficiency 626:643 b3galt5 deficiency 626:643 We also demonstrated that b3galt5 deficiency suppressed hepatocarcinogenesis in DEN/TCPOBOP-induced HCC. 36495345 1 14 theme Hepatocellular 103:116 arg1 HCC 129:131 HCC 129:131 HCC 129:131 Hepatocellular carcinoma (HCC) is one of the most common malignancies with high morbidity and mortality. 36495345 1 14 theme Hepatocellular 103:116 arg1 carcinoma 118:126 Hepatocellular carcinoma 103:126 Hepatocellular carcinoma (HCC) 103:132 Hepatocellular carcinoma (HCC) is one of the most common malignancies with high morbidity and mortality. 36495345 5 15 dep proliferation 559:571 arg1 the 555:557 the 555:557 the 555:557 In vitro studies showed that b3galt5 promoted the proliferation and survival of HCC cells. 36495345 10 16 theme potential 1186:1194 arg1 axis 1176:1179 the b3galt5-mTOR/p70s6k axis 1152:1179 the b3galt5-mTOR/p70s6k axis 1152:1179 Our study uncovers a novel mechanism by which b3galt5 mediates glycolysis in HCC and highlights the b3galt5-mTOR/p70s6k axis as a potential target for HCC therapy. 36495345 10 16 theme potential 1186:1194 arg1 target 1196:1201 a potential target 1184:1201 a potential target for HCC therapy 1184:1217 Our study uncovers a novel mechanism by which b3galt5 mediates glycolysis in HCC and highlights the b3galt5-mTOR/p70s6k axis as a potential target for HCC therapy. 36495345 4 17 from prognosis 482:490 arg1 patients 499:506 HCC patients 495:506 HCC patients 495:506 We found that b3galt5 is highly expressed and associated with a poor prognosis in HCC patients. 36495345 3 18 theme b3galt5 397:403 arg1 role 364:367 role 364:367 role 364:367 Here, we investigated the role and underlying mechanism of b3galt5 in HCC. 36495345 3 18 theme b3galt5 397:403 arg1 mechanism 384:392 underlying mechanism 373:392 underlying mechanism 373:392 Here, we investigated the role and underlying mechanism of b3galt5 in HCC. 36495345 5 19 theme In 509:510 arg1 studies 518:524 In vitro studies 509:524 In vitro studies 509:524 In vitro studies showed that b3galt5 promoted the proliferation and survival of HCC cells. 36495345 0 20 theme B3galt5 0:6 arg1 deficiency 8:17 B3galt5 deficiency 0:17 B3galt5 deficiency 0:17 B3galt5 deficiency attenuates hepatocellular carcinoma by suppressing mTOR/p70s6k-mediated glycolysis. 36495345 0 21 theme hepatocellular 30:43 arg1 carcinoma 45:53 hepatocellular carcinoma 30:53 hepatocellular carcinoma 30:53 B3galt5 deficiency attenuates hepatocellular carcinoma by suppressing mTOR/p70s6k-mediated glycolysis. 36495345 10 22 theme novel 1077:1081 arg1 mechanism 1083:1091 a novel mechanism 1075:1091 a novel mechanism by which b3galt5 mediates glycolysis in HCC and highlights the b3galt5-mTOR/p70s6k axis as a potential target for HCC therapy 1075:1217 Our study uncovers a novel mechanism by which b3galt5 mediates glycolysis in HCC and highlights the b3galt5-mTOR/p70s6k axis as a potential target for HCC therapy. 36495345 9 23 theme p70s6k 932:937 arg1 inhibition 939:948 p70s6k inhibition 932:948 p70s6k inhibition 932:948 Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. 36495345 5 24 theme HCC 589:591 arg1 cells 593:597 HCC cells 589:597 HCC cells 589:597 In vitro studies showed that b3galt5 promoted the proliferation and survival of HCC cells. 36495345 10 25 theme HCC 1207:1209 arg1 therapy 1211:1217 HCC therapy 1207:1217 HCC therapy 1207:1217 Our study uncovers a novel mechanism by which b3galt5 mediates glycolysis in HCC and highlights the b3galt5-mTOR/p70s6k axis as a potential target for HCC therapy. 36495345 3 26 from role 364:367 arg1 HCC 408:410 HCC 408:410 HCC 408:410 Here, we investigated the role and underlying mechanism of b3galt5 in HCC. 36495345 8 27 theme glycosylation 886:898 arg1 modification 900:911 O-linked glycosylation modification 877:911 O-linked glycosylation modification on mTOR 877:919 Mechanistically, b3galt5 promoted glycolysis by activating the mTOR/p70s6k pathway through O-linked glycosylation modification on mTOR. 36495345 9 28 from rate 1018:1021 arg1 cells 1049:1053 b3galt5-overexpressing cells 1026:1053 b3galt5-overexpressing cells 1026:1053 Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. 36495345 2 29 theme crucial 257:263 arg1 roles 265:269 crucial roles 257:269 crucial roles 257:269 Beta-1,3-galactosyltransferase 5 (b3galt5) plays crucial roles in protein glycosylation, but its function in HCC remains unclear. 36495345 0 30 theme mTOR/p70s6k-mediated 70:89 arg1 glycolysis 91:100 mTOR/p70s6k-mediated glycolysis 70:100 mTOR/p70s6k-mediated glycolysis 70:100 B3galt5 deficiency attenuates hepatocellular carcinoma by suppressing mTOR/p70s6k-mediated glycolysis. 36495345 8 31 link O-linked 877:884 arg1 modification 900:911 O-linked glycosylation modification 877:911 O-linked glycosylation modification on mTOR 877:919 Mechanistically, b3galt5 promoted glycolysis by activating the mTOR/p70s6k pathway through O-linked glycosylation modification on mTOR. 36495345 5 32 dep In 509:510 arg1 vitro 512:516 vitro 512:516 vitro 512:516 In vitro studies showed that b3galt5 promoted the proliferation and survival of HCC cells. 36495345 3 33 dep role 364:367 arg1 the 360:362 the 360:362 the 360:362 Here, we investigated the role and underlying mechanism of b3galt5 in HCC. 36495345 7 34 theme Further 705:711 arg1 investigation 713:725 Further investigation 705:725 Further investigation 705:725 Further investigation confirmed that b3galt5 promoted aerobic glycolysis in HCC. 36495345 6 35 theme DEN/TCPOBOP-induced 680:698 arg1 HCC 700:702 DEN/TCPOBOP-induced HCC 680:702 DEN/TCPOBOP-induced HCC 680:702 We also demonstrated that b3galt5 deficiency suppressed hepatocarcinogenesis in DEN/TCPOBOP-induced HCC. 36495345 9 36 theme key 976:978 arg1 enzymes 991:997 key glycolytic enzymes 976:997 key glycolytic enzymes 976:997 Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. 36495345 8 37 theme O-linked 877:884 arg1 modification 900:911 O-linked glycosylation modification 877:911 O-linked glycosylation modification on mTOR 877:919 Mechanistically, b3galt5 promoted glycolysis by activating the mTOR/p70s6k pathway through O-linked glycosylation modification on mTOR. 36495345 9 38 theme glycolytic 980:989 arg1 enzymes 991:997 key glycolytic enzymes 976:997 key glycolytic enzymes 976:997 Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. 36495345 9 39 theme enzymes 991:997 arg1 rate 1018:1021 the glycolysis rate 1003:1021 the glycolysis rate in b3galt5-overexpressing cells 1003:1053 Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. 36495345 9 39 theme enzymes 991:997 arg1 expression 962:971 the expression 958:971 the expression of key glycolytic enzymes 958:997 Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. 36495345 2 40 theme protein 274:280 arg1 glycosylation 282:294 protein glycosylation 274:294 protein glycosylation 274:294 Beta-1,3-galactosyltransferase 5 (b3galt5) plays crucial roles in protein glycosylation, but its function in HCC remains unclear. 36495345 1 41 theme common 153:158 arg1 malignancies 160:171 the most common malignancies 144:171 the most common malignancies with high morbidity and mortality 144:205 Hepatocellular carcinoma (HCC) is one of the most common malignancies with high morbidity and mortality. 36495345 2 42 from function 305:312 arg1 HCC 317:319 HCC 317:319 HCC 317:319 Beta-1,3-galactosyltransferase 5 (b3galt5) plays crucial roles in protein glycosylation, but its function in HCC remains unclear. 36495345 9 43 from expression 962:971 arg1 cells 1049:1053 b3galt5-overexpressing cells 1026:1053 b3galt5-overexpressing cells 1026:1053 Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. 36495345 1 44 theme malignancies 160:171 arg1 malignancies 160:171 the most common malignancies 144:171 the most common malignancies with high morbidity and mortality 144:205 Hepatocellular carcinoma (HCC) is one of the most common malignancies with high morbidity and mortality. 36495345 1 44 theme malignancies 160:171 arg1 one 137:139 one 137:139 one 137:139 Hepatocellular carcinoma (HCC) is one of the most common malignancies with high morbidity and mortality. 36029403 12 0 theme starting 2141:2148 arg1 point 2150:2154 an important starting point 2128:2154 an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets 2128:2297 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 9 1 theme proneural 1423:1431 arg1 subtypes 1447:1454 the proneural and classical subtypes 1419:1454 the proneural and classical subtypes 1419:1454 A total of 68 genes were differentially regulated in the most aggressive, mesenchymal subtype of GBM compared to the proneural and classical subtypes, and the expression of these genes was compared to normal brain tissues. 36029403 10 2 theme MGAT 1826:1829 arg1 SLC 1899:1901 SLC 1899:1901 SLC 1899:1901 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 2 theme MGAT 1826:1829 arg1 sialidase 1836:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 9 3 theme classical 1437:1445 arg1 subtypes 1447:1454 the proneural and classical subtypes 1419:1454 the proneural and classical subtypes 1419:1454 A total of 68 genes were differentially regulated in the most aggressive, mesenchymal subtype of GBM compared to the proneural and classical subtypes, and the expression of these genes was compared to normal brain tissues. 36029403 11 4 theme differential 1941:1952 arg1 expression 1954:1963 The differential expression 1937:1963 The differential expression of some genes 1937:1977 The differential expression of some genes was already reported in several solid tumors; however, several of them were found to be dysregulated in GBM for the first time. 36029403 12 5 theme diagnostic 2264:2273 arg1 role 2229:2232 the role 2225:2232 the role of these glycogenes in GBM 2225:2259 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 12 5 theme diagnostic 2264:2273 arg1 targets 2291:2297 diagnostic and therapeutic targets 2264:2297 diagnostic and therapeutic targets 2264:2297 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 10 6 theme acetylglucosaminyltransferase 1795:1823 arg1 SLC 1899:1901 SLC 1899:1901 SLC 1899:1901 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 6 theme acetylglucosaminyltransferase 1795:1823 arg1 sialidase 1836:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 2 7 theme glycoconjugates 275:289 arg1 biosynthesis 259:270 The biosynthesis 255:270 The biosynthesis of glycoconjugates 255:289 The biosynthesis of glycoconjugates is regulated through concerted and finely tuned enzymatic reactions. 36029403 6 8 theme GBM 906:908 arg1 aggressiveness 910:923 GBM aggressiveness 906:923 GBM aggressiveness 906:923 Several biomolecular features associated with GBM aggressiveness have been elucidated; however, more studies are needed to elucidate the role of glycosylation in GBM pathology, looking at their potential as cancer targets. 36029403 12 9 theme therapeutic 2279:2289 arg1 role 2229:2232 the role 2225:2232 the role of these glycogenes in GBM 2225:2259 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 12 9 theme therapeutic 2279:2289 arg1 targets 2291:2297 diagnostic and therapeutic targets 2264:2297 diagnostic and therapeutic targets 2264:2297 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 8 10 theme astrocytoma-TCGA-RNAseq 1247:1269 arg1 datasets 1271:1278 astrocytoma-TCGA-RNAseq datasets 1247:1278 astrocytoma-TCGA-RNAseq datasets from public repositories 1247:1303 Specifically, the mRNA levels of glycogenes were analyzed using astrocytoma-TCGA-RNAseq datasets from public repositories. 36029403 12 11 theme glycogenes 2243:2252 arg1 role 2229:2232 the role 2225:2232 the role of these glycogenes in GBM 2225:2259 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 12 11 theme glycogenes 2243:2252 arg1 targets 2291:2297 diagnostic and therapeutic targets 2264:2297 diagnostic and therapeutic targets 2264:2297 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 2 12 theme concerted 312:320 arg1 reactions 349:357 concerted and finely tuned enzymatic reactions 312:357 concerted and finely tuned enzymatic reactions 312:357 The biosynthesis of glycoconjugates is regulated through concerted and finely tuned enzymatic reactions. 36029403 10 13 theme GALNT 1737:1741 arg1 SLC 1899:1901 SLC 1899:1901 SLC 1899:1901 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 13 theme GALNT 1737:1741 arg1 sialidase 1836:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 1 14 theme immune 211:216 arg1 regulation 218:227 immune regulation 211:227 immune regulation 211:227 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 8 15 theme glycogenes 1216:1225 arg1 levels 1206:1211 the mRNA levels 1197:1211 the mRNA levels of glycogenes 1197:1225 Specifically, the mRNA levels of glycogenes were analyzed using astrocytoma-TCGA-RNAseq datasets from public repositories. 36029403 0 16 from Emphasis 54:61 arg1 Glioblastoma 66:77 Glioblastoma 66:77 Glioblastoma 66:77 Aberrant Protein Glycosylation in Brain Cancers, with Emphasis on Glioblastoma. 36029403 10 17 theme acetylgalactosaminyltransferases 1703:1734 arg1 SLC 1899:1901 SLC 1899:1901 SLC 1899:1901 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 17 theme acetylgalactosaminyltransferases 1703:1734 arg1 sialidase 1836:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 6 18 theme more 956:959 arg1 studies 961:967 more studies 956:967 more studies 956:967 Several biomolecular features associated with GBM aggressiveness have been elucidated; however, more studies are needed to elucidate the role of glycosylation in GBM pathology, looking at their potential as cancer targets. 36029403 7 19 link O-linked 1152:1159 arg1 glycosylation 1161:1173 O-linked glycosylation 1152:1173 O-linked glycosylation in GBM 1152:1180 Here, we focus on the alteration of genes involved in protein N- and O-linked glycosylation in GBM. 36029403 5 20 theme World 727:731 arg1 Organization 740:751 the World Health Organization (WHO) 723:757 the World Health Organization (WHO) 723:757 GBM has been classified by the World Health Organization (WHO) as a grade 4 astrocytoma and stratified into G-CIMP, proneural, classical, and mesenchymal subtypes. 36029403 8 21 from repositories 1292:1303 arg1 datasets 1271:1278 astrocytoma-TCGA-RNAseq datasets 1247:1278 astrocytoma-TCGA-RNAseq datasets from public repositories 1247:1303 Specifically, the mRNA levels of glycogenes were analyzed using astrocytoma-TCGA-RNAseq datasets from public repositories. 36029403 9 22 theme normal 1507:1512 arg1 tissues 1520:1526 normal brain tissues 1507:1526 normal brain tissues 1507:1526 A total of 68 genes were differentially regulated in the most aggressive, mesenchymal subtype of GBM compared to the proneural and classical subtypes, and the expression of these genes was compared to normal brain tissues. 36029403 10 23 dep fucosyltransferase 1674:1691 arg1 3 1671:1671 3 1671:1671 3 1671:1671 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 1 24 from signaling 173:181 arg1 migration 184:192 migration 184:192 migration 184:192 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 1 24 from signaling 173:181 arg1 processes 136:144 several processes 128:144 several processes of tumorigenesis from cell signaling 128:181 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 1 24 from signaling 173:181 arg1 invasion 198:205 invasion 198:205 invasion 198:205 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 1 25 theme tumorigenesis 149:161 arg1 migration 184:192 migration 184:192 migration 184:192 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 1 25 theme tumorigenesis 149:161 arg1 processes 136:144 several processes 128:144 several processes of tumorigenesis from cell signaling 128:181 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 1 25 theme tumorigenesis 149:161 arg1 invasion 198:205 invasion 198:205 invasion 198:205 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 11 26 theme solid 2011:2015 arg1 tumors 2017:2022 several solid tumors 2003:2022 several solid tumors 2003:2022 The differential expression of some genes was already reported in several solid tumors; however, several of them were found to be dysregulated in GBM for the first time. 36029403 0 27 from Glycosylation 17:29 arg1 Cancers 40:46 Brain Cancers 34:46 Brain Cancers 34:46 Aberrant Protein Glycosylation in Brain Cancers, with Emphasis on Glioblastoma. 36029403 1 28 theme cell 168:171 arg1 signaling 173:181 cell signaling 168:181 cell signaling 168:181 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 10 29 theme solute 1873:1878 arg1 family 1891:1896 9) solute carrier 35 family 1870:1896 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC) 1700:1902 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 7 30 from glycosylation 1161:1173 arg1 GBM 1178:1180 GBM 1178:1180 GBM 1178:1180 Here, we focus on the alteration of genes involved in protein N- and O-linked glycosylation in GBM. 36029403 3 31 theme substrate 469:477 arg1 glycosyltransferases 401:420 glycosyltransferases 401:420 glycosyltransferases 401:420 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 3 31 theme substrate 469:477 arg1 availability 479:490 substrate availability 469:490 substrate availability 469:490 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 5 32 theme grade 764:768 arg1 astrocytoma 772:782 a grade 4 astrocytoma 762:782 a grade 4 astrocytoma 762:782 GBM has been classified by the World Health Organization (WHO) as a grade 4 astrocytoma and stratified into G-CIMP, proneural, classical, and mesenchymal subtypes. 36029403 5 32 theme grade 764:768 arg1 GBM 696:698 GBM 696:698 GBM 696:698 GBM has been classified by the World Health Organization (WHO) as a grade 4 astrocytoma and stratified into G-CIMP, proneural, classical, and mesenchymal subtypes. 36029403 11 33 theme genes 1973:1977 arg1 expression 1954:1963 The differential expression 1937:1963 The differential expression of some genes 1937:1977 The differential expression of some genes was already reported in several solid tumors; however, several of them were found to be dysregulated in GBM for the first time. 36029403 10 34 theme glycosylation 1614:1626 arg1 glycosyltransferases 1638:1657 : 1) asparagine glycosylation (ALG); 2) glycosyltransferases 1598:1657 : 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T) 1598:1668 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 34 theme glycosylation 1614:1626 arg1 B4T 1665:1667 B4T 1665:1667 B4T 1665:1667 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 0 35 theme Aberrant 0:7 arg1 Glycosylation 17:29 Aberrant Protein Glycosylation 0:29 Aberrant Protein Glycosylation 0:29 Aberrant Protein Glycosylation in Brain Cancers, with Emphasis on Glioblastoma. 36029403 4 36 theme aggressive 577:586 arg1 Glioblastoma 546:557 Glioblastoma 546:557 Glioblastoma (GBM) 546:563 Glioblastoma (GBM) is the most aggressive brain tumor, frequently occurring in adults with overall survival not surpassing 17 months after diagnosis. 36029403 4 36 theme aggressive 577:586 arg1 tumor 594:598 the most aggressive brain tumor 568:598 the most aggressive brain tumor 568:598 Glioblastoma (GBM) is the most aggressive brain tumor, frequently occurring in adults with overall survival not surpassing 17 months after diagnosis. 36029403 3 37 theme nucleotide 440:449 arg1 glycosyltransferases 401:420 glycosyltransferases 401:420 glycosyltransferases 401:420 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 3 37 theme nucleotide 440:449 arg1 metabolism 457:466 nucleotide sugar metabolism 440:466 nucleotide sugar metabolism 440:466 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 6 38 from role 997:1000 arg1 pathology 1026:1034 GBM pathology 1022:1034 GBM pathology 1022:1034 Several biomolecular features associated with GBM aggressiveness have been elucidated; however, more studies are needed to elucidate the role of glycosylation in GBM pathology, looking at their potential as cancer targets. 36029403 0 39 theme Brain 34:38 arg1 Cancers 40:46 Brain Cancers 34:46 Brain Cancers 34:46 Aberrant Protein Glycosylation in Brain Cancers, with Emphasis on Glioblastoma. 36029403 9 40 theme aggressive 1368:1377 arg1 subtype 1392:1398 the most aggressive, mesenchymal subtype 1359:1398 the most aggressive, mesenchymal subtype of GBM 1359:1405 A total of 68 genes were differentially regulated in the most aggressive, mesenchymal subtype of GBM compared to the proneural and classical subtypes, and the expression of these genes was compared to normal brain tissues. 36029403 3 41 theme sugar 451:455 arg1 glycosyltransferases 401:420 glycosyltransferases 401:420 glycosyltransferases 401:420 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 3 41 theme sugar 451:455 arg1 metabolism 457:466 nucleotide sugar metabolism 440:466 nucleotide sugar metabolism 440:466 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 3 42 theme glycosidases 426:437 arg1 activity 389:396 activity 389:396 activity 389:396 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 3 42 theme glycosidases 426:437 arg1 levels 378:383 levels 378:383 levels 378:383 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 12 43 theme functional 2190:2199 arg1 validations 2201:2211 further orthogonal and functional validations 2167:2211 further orthogonal and functional validations 2167:2211 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 0 44 with Glycosylation 17:29 arg1 Emphasis 54:61 Emphasis 54:61 Emphasis on Glioblastoma 54:77 Aberrant Protein Glycosylation in Brain Cancers, with Emphasis on Glioblastoma. 36029403 3 45 theme functional 528:537 arg1 glycosyltransferases 401:420 glycosyltransferases 401:420 glycosyltransferases 401:420 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 3 45 theme functional 528:537 arg1 state 539:543 cellular functional state 519:543 cellular functional state 519:543 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 7 46 theme protein 1137:1143 arg1 N- 1145:1146 protein N- 1137:1146 protein N- 1137:1146 Here, we focus on the alteration of genes involved in protein N- and O-linked glycosylation in GBM. 36029403 6 47 theme Several 860:866 arg1 features 881:888 Several biomolecular features 860:888 Several biomolecular features associated with GBM aggressiveness 860:923 Several biomolecular features associated with GBM aggressiveness have been elucidated; however, more studies are needed to elucidate the role of glycosylation in GBM pathology, looking at their potential as cancer targets. 36029403 3 48 dep levels 378:383 arg1 the 374:376 the 374:376 the 374:376 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 10 49 theme mannosidase 1773:1783 arg1 SLC 1899:1901 SLC 1899:1901 SLC 1899:1901 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 49 theme mannosidase 1773:1783 arg1 sialidase 1836:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 50 dep glycosylation 1614:1626 arg1 1 1600:1600 1 1600:1600 1 1600:1600 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 6 51 gly glycosylation 1005:1017 arg1 GBM 1022:1024 GBM pathology 1022:1034 GBM pathology 1022:1034 Several biomolecular features associated with GBM aggressiveness have been elucidated; however, more studies are needed to elucidate the role of glycosylation in GBM pathology, looking at their potential as cancer targets. 36029403 7 52 gly glycosylation 1161:1173 arg1 GBM 1178:1180 GBM 1178:1180 GBM 1178:1180 Here, we focus on the alteration of genes involved in protein N- and O-linked glycosylation in GBM. 36029403 1 53 theme metastasis 233:242 arg1 formation 244:252 metastasis formation 233:252 metastasis formation 233:252 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 12 54 theme orthogonal 2175:2184 arg1 validations 2201:2211 further orthogonal and functional validations 2167:2211 further orthogonal and functional validations 2167:2211 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 7 55 theme genes 1119:1123 arg1 alteration 1105:1114 the alteration 1101:1114 the alteration of genes involved in protein N- and O-linked glycosylation in GBM 1101:1180 Here, we focus on the alteration of genes involved in protein N- and O-linked glycosylation in GBM. 36029403 10 56 dep sialidase 1836:1844 arg1 family 1891:1896 9) solute carrier 35 family 1870:1896 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC) 1700:1902 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 56 dep sialidase 1836:1844 arg1 4 1700:1700 4 1700:1700 4 1700:1700 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 12 57 theme important 2131:2139 arg1 point 2150:2154 an important starting point 2128:2154 an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets 2128:2297 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 10 58 theme MAN 1786:1788 arg1 SLC 1899:1901 SLC 1899:1901 SLC 1899:1901 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 58 theme MAN 1786:1788 arg1 sialidase 1836:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 2 59 theme tuned 333:337 arg1 reactions 349:357 concerted and finely tuned enzymatic reactions 312:357 concerted and finely tuned enzymatic reactions 312:357 The biosynthesis of glycoconjugates is regulated through concerted and finely tuned enzymatic reactions. 36029403 5 60 theme Health 733:738 arg1 Organization 740:751 the World Health Organization (WHO) 723:757 the World Health Organization (WHO) 723:757 GBM has been classified by the World Health Organization (WHO) as a grade 4 astrocytoma and stratified into G-CIMP, proneural, classical, and mesenchymal subtypes. 36029403 5 61 theme mesenchymal 838:848 arg1 subtypes 850:857 mesenchymal subtypes 838:857 mesenchymal subtypes 838:857 GBM has been classified by the World Health Organization (WHO) as a grade 4 astrocytoma and stratified into G-CIMP, proneural, classical, and mesenchymal subtypes. 36029403 12 62 from role 2229:2232 arg1 GBM 2257:2259 GBM 2257:2259 GBM 2257:2259 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 8 63 theme mRNA 1201:1204 arg1 levels 1206:1211 the mRNA levels 1197:1211 the mRNA levels of glycogenes 1197:1225 Specifically, the mRNA levels of glycogenes were analyzed using astrocytoma-TCGA-RNAseq datasets from public repositories. 36029403 8 64 theme public 1285:1290 arg1 repositories 1292:1303 public repositories 1285:1303 public repositories 1285:1303 Specifically, the mRNA levels of glycogenes were analyzed using astrocytoma-TCGA-RNAseq datasets from public repositories. 36029403 10 65 theme hexosaminidase 1748:1761 arg1 SLC 1899:1901 SLC 1899:1901 SLC 1899:1901 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 65 theme hexosaminidase 1748:1761 arg1 sialidase 1836:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 1 66 theme several 128:134 arg1 migration 184:192 migration 184:192 migration 184:192 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 1 66 theme several 128:134 arg1 processes 136:144 several processes 128:144 several processes of tumorigenesis from cell signaling 128:181 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 1 66 theme several 128:134 arg1 invasion 198:205 invasion 198:205 invasion 198:205 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 9 67 theme brain 1514:1518 arg1 tissues 1520:1526 normal brain tissues 1507:1526 normal brain tissues 1507:1526 A total of 68 genes were differentially regulated in the most aggressive, mesenchymal subtype of GBM compared to the proneural and classical subtypes, and the expression of these genes was compared to normal brain tissues. 36029403 12 68 theme further 2167:2173 arg1 validations 2201:2211 further orthogonal and functional validations 2167:2211 further orthogonal and functional validations 2167:2211 These data represent an important starting point to perform further orthogonal and functional validations to pinpoint the role of these glycogenes in GBM as diagnostic and therapeutic targets. 36029403 6 69 theme GBM 1022:1024 arg1 pathology 1026:1034 GBM pathology 1022:1034 GBM pathology 1022:1034 Several biomolecular features associated with GBM aggressiveness have been elucidated; however, more studies are needed to elucidate the role of glycosylation in GBM pathology, looking at their potential as cancer targets. 36029403 5 70 dep Organization 740:751 arg1 WHO 754:756 WHO 754:756 WHO 754:756 GBM has been classified by the World Health Organization (WHO) as a grade 4 astrocytoma and stratified into G-CIMP, proneural, classical, and mesenchymal subtypes. 36029403 7 71 from N- 1145:1146 arg1 GBM 1178:1180 GBM 1178:1180 GBM 1178:1180 Here, we focus on the alteration of genes involved in protein N- and O-linked glycosylation in GBM. 36029403 10 72 theme carrier 1880:1886 arg1 family 1891:1896 9) solute carrier 35 family 1870:1896 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC) 1700:1902 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 6 73 theme glycosylation 1005:1017 arg1 role 997:1000 the role 993:1000 the role of glycosylation in GBM pathology 993:1034 Several biomolecular features associated with GBM aggressiveness have been elucidated; however, more studies are needed to elucidate the role of glycosylation in GBM pathology, looking at their potential as cancer targets. 36029403 11 74 theme them 2045:2048 arg1 several 2034:2040 several 2034:2040 several 2034:2040 The differential expression of some genes was already reported in several solid tumors; however, several of them were found to be dysregulated in GBM for the first time. 36029403 2 75 theme enzymatic 339:347 arg1 reactions 349:357 concerted and finely tuned enzymatic reactions 312:357 concerted and finely tuned enzymatic reactions 312:357 The biosynthesis of glycoconjugates is regulated through concerted and finely tuned enzymatic reactions. 36029403 9 76 theme genes 1320:1324 arg1 total 1308:1312 A total 1306:1312 A total of 68 genes 1306:1324 A total of 68 genes were differentially regulated in the most aggressive, mesenchymal subtype of GBM compared to the proneural and classical subtypes, and the expression of these genes was compared to normal brain tissues. 36029403 9 77 dep aggressive 1368:1377 arg1 mesenchymal 1380:1390 mesenchymal 1380:1390 mesenchymal 1380:1390 A total of 68 genes were differentially regulated in the most aggressive, mesenchymal subtype of GBM compared to the proneural and classical subtypes, and the expression of these genes was compared to normal brain tissues. 36029403 0 78 theme Protein 9:15 arg1 Glycosylation 17:29 Aberrant Protein Glycosylation 0:29 Aberrant Protein Glycosylation 0:29 Aberrant Protein Glycosylation in Brain Cancers, with Emphasis on Glioblastoma. 36029403 1 79 theme Aberrant 80:87 arg1 glycosylation 89:101 Aberrant glycosylation 80:101 Aberrant glycosylation 80:101 Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. 36029403 4 80 theme brain 588:592 arg1 Glioblastoma 546:557 Glioblastoma 546:557 Glioblastoma (GBM) 546:563 Glioblastoma (GBM) is the most aggressive brain tumor, frequently occurring in adults with overall survival not surpassing 17 months after diagnosis. 36029403 4 80 theme brain 588:592 arg1 tumor 594:598 the most aggressive brain tumor 568:598 the most aggressive brain tumor 568:598 Glioblastoma (GBM) is the most aggressive brain tumor, frequently occurring in adults with overall survival not surpassing 17 months after diagnosis. 36029403 10 81 theme asparagine 1603:1612 arg1 ALG 1629:1631 ALG); 2 1629:1635 ALG); 2 1629:1635 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 81 theme asparagine 1603:1612 arg1 glycosylation 1614:1626 : 1) asparagine glycosylation 1598:1626 : 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T) 1598:1668 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 7 82 theme O-linked 1152:1159 arg1 glycosylation 1161:1173 O-linked glycosylation 1152:1173 O-linked glycosylation in GBM 1152:1180 Here, we focus on the alteration of genes involved in protein N- and O-linked glycosylation in GBM. 36029403 6 83 theme cancer 1067:1072 arg1 targets 1074:1080 cancer targets 1067:1080 cancer targets 1067:1080 Several biomolecular features associated with GBM aggressiveness have been elucidated; however, more studies are needed to elucidate the role of glycosylation in GBM pathology, looking at their potential as cancer targets. 36029403 4 84 with adults 625:630 arg1 survival 645:652 overall survival 637:652 overall survival not surpassing 17 months after diagnosis 637:693 Glioblastoma (GBM) is the most aggressive brain tumor, frequently occurring in adults with overall survival not surpassing 17 months after diagnosis. 36029403 11 85 theme several 2003:2009 arg1 tumors 2017:2022 several solid tumors 2003:2022 several solid tumors 2003:2022 The differential expression of some genes was already reported in several solid tumors; however, several of them were found to be dysregulated in GBM for the first time. 36029403 10 86 theme HEX 1764:1766 arg1 SLC 1899:1901 SLC 1899:1901 SLC 1899:1901 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 10 86 theme HEX 1764:1766 arg1 sialidase 1836:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase 1703:1844 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 3 87 theme epigenetic 493:502 arg1 glycosyltransferases 401:420 glycosyltransferases 401:420 glycosyltransferases 401:420 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 3 87 theme epigenetic 493:502 arg1 condition 504:512 epigenetic condition 493:512 epigenetic condition 493:512 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 6 88 theme biomolecular 868:879 arg1 features 881:888 Several biomolecular features 860:888 Several biomolecular features associated with GBM aggressiveness 860:923 Several biomolecular features associated with GBM aggressiveness have been elucidated; however, more studies are needed to elucidate the role of glycosylation in GBM pathology, looking at their potential as cancer targets. 36029403 4 89 theme overall 637:643 arg1 survival 645:652 overall survival 637:652 overall survival not surpassing 17 months after diagnosis 637:693 Glioblastoma (GBM) is the most aggressive brain tumor, frequently occurring in adults with overall survival not surpassing 17 months after diagnosis. 36029403 3 90 theme cellular 519:526 arg1 glycosyltransferases 401:420 glycosyltransferases 401:420 glycosyltransferases 401:420 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 3 90 theme cellular 519:526 arg1 state 539:543 cellular functional state 519:543 cellular functional state 519:543 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 9 91 theme GBM 1403:1405 arg1 subtype 1392:1398 the most aggressive, mesenchymal subtype 1359:1398 the most aggressive, mesenchymal subtype of GBM 1359:1405 A total of 68 genes were differentially regulated in the most aggressive, mesenchymal subtype of GBM compared to the proneural and classical subtypes, and the expression of these genes was compared to normal brain tissues. 36029403 9 92 theme genes 1485:1489 arg1 expression 1465:1474 the expression 1461:1474 the expression of these genes 1461:1489 A total of 68 genes were differentially regulated in the most aggressive, mesenchymal subtype of GBM compared to the proneural and classical subtypes, and the expression of these genes was compared to normal brain tissues. 36029403 10 93 dep sialyltransferase 1913:1929 arg1 ST 1932:1933 ST 1932:1933 ST 1932:1933 Among them, we focused on 38 genes coding for proteins that belong to: 1) asparagine glycosylation (ALG); 2) glycosyltransferases (B3T, B4T); 3) fucosyltransferase (FUT); 4) acetylgalactosaminyltransferases (GALNT); 5) hexosaminidase (HEX); 6) mannosidase (MAN); 7) acetylglucosaminyltransferase (MGAT); 8) sialidase or neuraminidase (NEU); 9) solute carrier 35 family (SLC); and 10) sialyltransferase (ST). 36029403 11 94 theme first 2095:2099 arg1 time 2101:2104 the first time 2091:2104 the first time 2091:2104 The differential expression of some genes was already reported in several solid tumors; however, several of them were found to be dysregulated in GBM for the first time. 36029403 3 95 theme glycosyltransferases 401:420 arg1 activity 389:396 activity 389:396 activity 389:396 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 36029403 3 95 theme glycosyltransferases 401:420 arg1 levels 378:383 levels 378:383 levels 378:383 This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. 35625551 0 0 from Regulation 20:29 arg1 Differentiation 72:86 Extraembryonic Endoderm Differentiation 48:86 Extraembryonic Endoderm Differentiation 48:86 O-GlcNAcylation and Regulation of Galectin-3 in Extraembryonic Endoderm Differentiation. 35625551 9 1 theme XEN 1645:1647 arg1 lineage 1649:1655 the XEN lineage 1641:1655 the XEN lineage 1641:1655 Inhibiting global O-GlcNAcylation status does not, however, impact pluripotency and the ability of ES cells to differentiate to the XEN lineage. 35625551 6 2 theme low 1035:1037 arg1 cells 1028:1032 XEN cells 1024:1032 XEN cells (low O-GlcNAc) 1024:1047 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 2 theme low 1035:1037 arg1 O-GlcNAc 1039:1046 low O-GlcNAc 1035:1046 low O-GlcNAc 1035:1046 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 5 3 theme dot 790:792 arg1 analysis 799:806 dot blot analysis 790:806 dot blot analysis 790:806 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 5 4 from disbalance 892:901 arg1 expression 910:919 the expression 906:919 the expression of genes encoding O-GlcNAc cycle enzymes 906:960 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 4 5 theme XEN 727:729 arg1 cells 731:735 XEN cells 727:735 XEN cells relative to embryonic stem (ES) cells 727:773 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 4 6 theme other 608:612 arg1 studies 614:620 other studies 608:620 other studies 608:620 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 0 7 from O-GlcNAcylation 0:14 arg1 Differentiation 72:86 Extraembryonic Endoderm Differentiation 48:86 Extraembryonic Endoderm Differentiation 48:86 O-GlcNAcylation and Regulation of Galectin-3 in Extraembryonic Endoderm Differentiation. 35625551 9 8 theme ES 1612:1613 arg1 cells 1615:1619 ES cells 1612:1619 ES cells 1612:1619 Inhibiting global O-GlcNAcylation status does not, however, impact pluripotency and the ability of ES cells to differentiate to the XEN lineage. 35625551 6 9 theme relative 1160:1167 arg1 secretion 1169:1177 the relative secretion 1156:1177 the relative secretion of galectin-3 1156:1191 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 4 10 from profile 716:722 arg1 levels 674:679 global O-GlcNAcylation levels 651:679 global O-GlcNAcylation levels 651:679 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 4 10 from profile 716:722 arg1 cells 731:735 XEN cells 727:735 XEN cells relative to embryonic stem (ES) cells 727:773 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 4 11 theme ES 765:766 arg1 cells 769:773 embryonic stem (ES) cells 749:773 embryonic stem (ES) cells 749:773 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 6 12 theme high 1140:1143 arg1 cells 1133:1137 ES cells 1130:1137 ES cells (high O-GlcNAc) 1130:1153 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 12 theme high 1140:1143 arg1 O-GlcNAc 1145:1152 high O-GlcNAc 1140:1152 high O-GlcNAc 1140:1152 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 3 13 theme extracellular 574:586 arg1 functions 588:596 various intracellular and extracellular functions 548:596 various intracellular and extracellular functions 548:596 Of the plethora of proteins regulated through O-GlcNAc, we explored galectin-3 as a candidate protein known to have various intracellular and extracellular functions. 35625551 4 14 theme embryonic 749:757 arg1 cells 769:773 embryonic stem (ES) cells 749:773 embryonic stem (ES) cells 749:773 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 5 15 theme global 843:848 arg1 O-GlcNAc 850:857 global O-GlcNAc 843:857 global O-GlcNAc 843:857 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 4 16 theme global 651:656 arg1 levels 674:679 global O-GlcNAcylation levels 651:679 global O-GlcNAcylation levels 651:679 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 3 17 theme various 548:554 arg1 functions 588:596 various intracellular and extracellular functions 548:596 various intracellular and extracellular functions 548:596 Of the plethora of proteins regulated through O-GlcNAc, we explored galectin-3 as a candidate protein known to have various intracellular and extracellular functions. 35625551 7 18 theme O-GlcNAcase 1286:1296 arg1 inhibitor 1298:1306 an O-GlcNAcase inhibitor 1283:1306 an O-GlcNAcase inhibitor 1283:1306 Inducing ES cells toward XEN in the presence of an O-GlcNAcase inhibitor was not sufficient to inhibit XEN differentiation. 35625551 4 19 theme distinct 687:694 arg1 profile 716:722 a distinct galectin expression profile 685:722 a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells 685:773 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 5 20 theme XEN 809:811 arg1 cells 813:817 XEN cells 809:817 XEN cells 809:817 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 3 21 theme intracellular 556:568 arg1 functions 588:596 various intracellular and extracellular functions 548:596 various intracellular and extracellular functions 548:596 Of the plethora of proteins regulated through O-GlcNAc, we explored galectin-3 as a candidate protein known to have various intracellular and extracellular functions. 35625551 6 22 theme lower 1053:1057 arg1 concentrations 1059:1072 lower concentrations 1053:1072 lower concentrations of both intracellular and extracellular galectin-3 1053:1123 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 2 23 theme post-translational 326:343 arg1 modifications 345:357 these post-translational modifications 320:357 these post-translational modifications 320:357 However, these post-translational modifications have not been explored in extraembryonic endoderm (XEN) differentiation. 35625551 4 24 theme expression 705:714 arg1 profile 716:722 a distinct galectin expression profile 685:722 a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells 685:773 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 6 25 theme Western 977:983 arg1 Immunoassays 963:974 Immunoassays 963:974 Immunoassays (Western blot and ELISA) 963:999 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 25 theme Western 977:983 arg1 blot 985:988 Western blot 977:988 Western blot 977:988 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 8 26 theme galectin-3 1475:1484 arg1 localization 1459:1470 the extracellular localization 1441:1470 the extracellular localization of galectin-3 1441:1484 However, global O-GlcNAcylation was found to decrease in differentiated cells and the extracellular localization of galectin-3 accompanies these changes. 35625551 5 27 theme ES 864:865 arg1 cells 867:871 ES cells 864:871 ES cells 864:871 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 1 28 theme proteins 107:114 arg1 regulation 93:102 The regulation 89:102 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) 89:192 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 7 29 theme XEN 1338:1340 arg1 differentiation 1342:1356 XEN differentiation 1338:1356 XEN differentiation 1338:1356 Inducing ES cells toward XEN in the presence of an O-GlcNAcase inhibitor was not sufficient to inhibit XEN differentiation. 35625551 3 30 theme proteins 451:458 arg1 plethora 439:446 the plethora 435:446 the plethora of proteins regulated through O-GlcNAc 435:485 Of the plethora of proteins regulated through O-GlcNAc, we explored galectin-3 as a candidate protein known to have various intracellular and extracellular functions. 35625551 5 31 theme decreased 823:831 arg1 levels 833:838 decreased levels 823:838 decreased levels of global O-GlcNAc 823:857 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 5 32 theme genes 924:928 arg1 expression 910:919 the expression 906:919 the expression of genes encoding O-GlcNAc cycle enzymes 906:960 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 5 33 theme cycle 948:952 arg1 enzymes 954:960 O-GlcNAc cycle enzymes 939:960 O-GlcNAc cycle enzymes 939:960 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 4 34 theme O-GlcNAcylation 658:672 arg1 levels 674:679 global O-GlcNAcylation levels 651:679 global O-GlcNAcylation levels 651:679 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 5 35 theme O-GlcNAc 939:946 arg1 enzymes 954:960 O-GlcNAc cycle enzymes 939:960 O-GlcNAc cycle enzymes 939:960 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 1 36 theme differentiation 294:308 arg1 regulation 280:289 the regulation 276:289 the regulation of differentiation 276:308 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 1 36 theme differentiation 294:308 arg1 cell 254:257 stem cell pluripotency and the regulation of differentiation 249:308 cell 254:257 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 1 37 dep addition 128:135 arg1 the 124:126 the 124:126 the 124:126 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 8 38 from decrease 1404:1411 arg1 cells 1431:1435 differentiated cells 1416:1435 differentiated cells 1416:1435 However, global O-GlcNAcylation was found to decrease in differentiated cells and the extracellular localization of galectin-3 accompanies these changes. 35625551 1 39 theme many 210:213 arg1 events 225:230 many signaling events 210:230 many signaling events 210:230 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 5 40 theme blot 794:797 arg1 analysis 799:806 dot blot analysis 790:806 dot blot analysis 790:806 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 4 41 theme relative 737:744 arg1 cells 731:735 XEN cells 727:735 XEN cells relative to embryonic stem (ES) cells 727:773 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 1 42 link O-linked 152:159 arg1 β-N-acetylglucosamine 161:181 O-linked β-N-acetylglucosamine 152:181 O-linked β-N-acetylglucosamine (O-GlcNAc) 152:192 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 1 42 link O-linked 152:159 arg1 O-GlcNAc 184:191 O-GlcNAc 184:191 O-GlcNAc 184:191 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 5 43 theme O-GlcNAc 850:857 arg1 levels 833:838 decreased levels 823:838 decreased levels of global O-GlcNAc 823:857 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 6 44 theme XEN 1224:1226 arg1 cells 1228:1232 XEN cells 1224:1232 XEN cells 1224:1232 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 4 45 theme galectin 696:703 arg1 profile 716:722 a distinct galectin expression profile 685:722 a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells 685:773 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 1 46 theme signaling 215:223 arg1 events 225:230 many signaling events 210:230 many signaling events 210:230 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 0 47 theme Galectin-3 34:43 arg1 Regulation 20:29 Regulation 20:29 Regulation 20:29 O-GlcNAcylation and Regulation of Galectin-3 in Extraembryonic Endoderm Differentiation. 35625551 0 47 theme Galectin-3 34:43 arg1 O-GlcNAcylation 0:14 O-GlcNAcylation 0:14 O-GlcNAcylation 0:14 O-GlcNAcylation and Regulation of Galectin-3 in Extraembryonic Endoderm Differentiation. 35625551 5 48 contain had 819:821 arg2 levels 833:838 decreased levels 823:838 decreased levels of global O-GlcNAc 823:857 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 5 48 contain had 819:821 arg1 cells 813:817 XEN cells 809:817 XEN cells 809:817 By conducting dot blot analysis, XEN cells had decreased levels of global O-GlcNAc than ES cells, which reflected a disbalance in the expression of genes encoding O-GlcNAc cycle enzymes. 35625551 8 49 theme global 1368:1373 arg1 O-GlcNAcylation 1375:1389 global O-GlcNAcylation 1368:1389 global O-GlcNAcylation 1368:1389 However, global O-GlcNAcylation was found to decrease in differentiated cells and the extracellular localization of galectin-3 accompanies these changes. 35625551 0 50 theme Endoderm 63:70 arg1 Differentiation 72:86 Extraembryonic Endoderm Differentiation 48:86 Extraembryonic Endoderm Differentiation 48:86 O-GlcNAcylation and Regulation of Galectin-3 in Extraembryonic Endoderm Differentiation. 35625551 9 51 theme impact 1573:1578 arg1 pluripotency 1580:1591 impact pluripotency 1573:1591 impact pluripotency 1573:1591 Inhibiting global O-GlcNAcylation status does not, however, impact pluripotency and the ability of ES cells to differentiate to the XEN lineage. 35625551 9 52 dep ability 1601:1607 arg1 differentiate 1624:1636 differentiate 1624:1636 to differentiate to the XEN lineage 1621:1655 Inhibiting global O-GlcNAcylation status does not, however, impact pluripotency and the ability of ES cells to differentiate to the XEN lineage. 35625551 6 53 contain had 1049:1051 arg2 concentrations 1059:1072 lower concentrations 1053:1072 lower concentrations of both intracellular and extracellular galectin-3 1053:1123 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 53 contain had 1049:1051 arg1 cells 1028:1032 XEN cells 1024:1032 XEN cells (low O-GlcNAc) 1024:1047 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 53 contain had 1049:1051 arg1 O-GlcNAc 1039:1046 low O-GlcNAc 1035:1046 low O-GlcNAc 1035:1046 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 54 theme ES 1130:1131 arg1 cells 1133:1137 ES cells 1130:1137 ES cells (high O-GlcNAc) 1130:1153 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 54 theme ES 1130:1131 arg1 O-GlcNAc 1145:1152 high O-GlcNAc 1140:1152 high O-GlcNAc 1140:1152 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 0 55 theme Extraembryonic 48:61 arg1 Differentiation 72:86 Extraembryonic Endoderm Differentiation 48:86 Extraembryonic Endoderm Differentiation 48:86 O-GlcNAcylation and Regulation of Galectin-3 in Extraembryonic Endoderm Differentiation. 35625551 7 56 theme inhibitor 1298:1306 arg1 presence 1271:1278 the presence 1267:1278 the presence of an O-GlcNAcase inhibitor 1267:1306 Inducing ES cells toward XEN in the presence of an O-GlcNAcase inhibitor was not sufficient to inhibit XEN differentiation. 35625551 6 57 dep Immunoassays 963:974 arg1 ELISA 994:998 ELISA 994:998 ELISA 994:998 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 57 dep Immunoassays 963:974 arg1 Immunoassays 963:974 Immunoassays 963:974 Immunoassays (Western blot and ELISA) 963:999 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 57 dep Immunoassays 963:974 arg1 blot 985:988 Western blot 977:988 Western blot 977:988 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 9 58 theme cells 1615:1619 arg1 pluripotency 1580:1591 impact pluripotency 1573:1591 impact pluripotency 1573:1591 Inhibiting global O-GlcNAcylation status does not, however, impact pluripotency and the ability of ES cells to differentiate to the XEN lineage. 35625551 9 58 theme cells 1615:1619 arg1 ability 1601:1607 the ability 1597:1607 the ability of ES cells to differentiate to the XEN lineage 1597:1655 Inhibiting global O-GlcNAcylation status does not, however, impact pluripotency and the ability of ES cells to differentiate to the XEN lineage. 35625551 3 59 theme candidate 516:524 arg1 galectin-3 500:509 galectin-3 500:509 galectin-3 500:509 Of the plethora of proteins regulated through O-GlcNAc, we explored galectin-3 as a candidate protein known to have various intracellular and extracellular functions. 35625551 3 59 theme candidate 516:524 arg1 protein 526:532 a candidate protein 514:532 a candidate protein known to have various intracellular and extracellular functions 514:596 Of the plethora of proteins regulated through O-GlcNAc, we explored galectin-3 as a candidate protein known to have various intracellular and extracellular functions. 35625551 7 60 theme ES 1244:1245 arg1 cells 1247:1251 ES cells 1244:1251 ES cells toward XEN 1244:1262 Inducing ES cells toward XEN in the presence of an O-GlcNAcase inhibitor was not sufficient to inhibit XEN differentiation. 35625551 1 61 theme O-linked 152:159 arg1 β-N-acetylglucosamine 161:181 O-linked β-N-acetylglucosamine 152:181 O-linked β-N-acetylglucosamine (O-GlcNAc) 152:192 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 1 61 theme O-linked 152:159 arg1 O-GlcNAc 184:191 O-GlcNAc 184:191 O-GlcNAc 184:191 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 9 62 theme O-GlcNAcylation 1531:1545 arg1 status 1547:1552 global O-GlcNAcylation status 1524:1552 global O-GlcNAcylation status 1524:1552 Inhibiting global O-GlcNAcylation status does not, however, impact pluripotency and the ability of ES cells to differentiate to the XEN lineage. 35625551 4 63 theme stem 759:762 arg1 cells 769:773 embryonic stem (ES) cells 749:773 embryonic stem (ES) cells 749:773 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 6 64 theme extracellular 1100:1112 arg1 galectin-3 1114:1123 both intracellular and extracellular galectin-3 1077:1123 both intracellular and extracellular galectin-3 1077:1123 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 65 theme XEN 1024:1026 arg1 cells 1028:1032 XEN cells 1024:1032 XEN cells (low O-GlcNAc) 1024:1047 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 6 65 theme XEN 1024:1026 arg1 O-GlcNAc 1039:1046 low O-GlcNAc 1035:1046 low O-GlcNAc 1035:1046 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 1 66 dep cell 254:257 arg1 pluripotency 259:270 pluripotency 259:270 pluripotency 259:270 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 6 67 theme galectin-3 1182:1191 arg1 secretion 1169:1177 the relative secretion 1156:1177 the relative secretion of galectin-3 1156:1191 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 1 68 theme β-N-acetylglucosamine 161:181 arg1 removal 141:147 removal 141:147 removal 141:147 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 1 68 theme β-N-acetylglucosamine 161:181 arg1 addition 128:135 addition 128:135 addition 128:135 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 35625551 6 69 theme galectin-3 1114:1123 arg1 concentrations 1059:1072 lower concentrations 1053:1072 lower concentrations of both intracellular and extracellular galectin-3 1053:1123 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 8 70 theme extracellular 1445:1457 arg1 localization 1459:1470 the extracellular localization 1441:1470 the extracellular localization of galectin-3 1441:1484 However, global O-GlcNAcylation was found to decrease in differentiated cells and the extracellular localization of galectin-3 accompanies these changes. 35625551 6 71 theme intracellular 1082:1094 arg1 galectin-3 1114:1123 both intracellular and extracellular galectin-3 1077:1123 both intracellular and extracellular galectin-3 1077:1123 Immunoassays (Western blot and ELISA) revealed that although XEN cells (low O-GlcNAc) had lower concentrations of both intracellular and extracellular galectin-3 than ES cells (high O-GlcNAc), the relative secretion of galectin-3 was significantly increased by XEN cells. 35625551 8 72 theme differentiated 1416:1429 arg1 cells 1431:1435 differentiated cells 1416:1435 differentiated cells 1416:1435 However, global O-GlcNAcylation was found to decrease in differentiated cells and the extracellular localization of galectin-3 accompanies these changes. 35625551 9 73 theme global 1524:1529 arg1 status 1547:1552 global O-GlcNAcylation status 1524:1552 global O-GlcNAcylation status 1524:1552 Inhibiting global O-GlcNAcylation status does not, however, impact pluripotency and the ability of ES cells to differentiate to the XEN lineage. 35625551 2 74 theme endoderm 400:407 arg1 differentiation 415:429 extraembryonic endoderm (XEN) differentiation 385:429 extraembryonic endoderm (XEN) differentiation 385:429 However, these post-translational modifications have not been explored in extraembryonic endoderm (XEN) differentiation. 35625551 4 75 from reduction 638:646 arg1 levels 674:679 global O-GlcNAcylation levels 651:679 global O-GlcNAcylation levels 651:679 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 4 75 from reduction 638:646 arg1 cells 731:735 XEN cells 727:735 XEN cells relative to embryonic stem (ES) cells 727:773 Based on other studies, we predicted a reduction in global O-GlcNAcylation levels and a distinct galectin expression profile in XEN cells relative to embryonic stem (ES) cells. 35625551 2 76 theme extraembryonic 385:398 arg1 XEN 410:412 XEN 410:412 XEN 410:412 However, these post-translational modifications have not been explored in extraembryonic endoderm (XEN) differentiation. 35625551 2 76 theme extraembryonic 385:398 arg1 endoderm 400:407 extraembryonic endoderm 385:407 extraembryonic endoderm (XEN) differentiation 385:429 However, these post-translational modifications have not been explored in extraembryonic endoderm (XEN) differentiation. 35625551 1 77 theme stem 249:252 arg1 cell 254:257 stem cell pluripotency and the regulation of differentiation 249:308 cell 254:257 The regulation of proteins through the addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) plays a role in many signaling events, specifically in stem cell pluripotency and the regulation of differentiation. 36112477 6 0 theme identified 572:581 arg1 glycopeptides 583:595 identified glycopeptides 572:595 identified glycopeptides in proteolytic digests of human milk 572:632 Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. 36112477 9 1 theme higher-energy 1135:1147 arg1 fragmentation 1182:1194 higher-energy (stepped) collision dissociation fragmentation 1135:1194 higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation 1135:1229 These were acquired by higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation. 36112477 7 2 theme distributions 909:921 arg1 comparison 882:891 the direct comparison 871:891 the direct comparison of glycopeptide distributions for individual proteins 871:945 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 9 3 theme stepped 1150:1156 arg1 fragmentation 1182:1194 higher-energy (stepped) collision dissociation fragmentation 1135:1194 higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation 1135:1229 These were acquired by higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation. 36112477 11 4 theme used 1348:1351 arg1 library 1362:1368 a widely used spectral library 1339:1368 a widely used spectral library search and display software 1339:1396 This data, with extensions of a widely used spectral library search and display software, provides accessible mass spectral libraries. 36112477 8 5 gly glycopeptide 1090:1101 arg2 glycopeptide 1090:1101 the underlying glycopeptide spectra 1075:1109 the underlying glycopeptide spectra 1075:1109 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 6 6 gly glycopeptides 583:595 arg2 glycopeptides 583:595 identified glycopeptides 572:595 identified glycopeptides in proteolytic digests of human milk 572:632 Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. 36112477 0 7 theme Milk 98:101 arg1 Proteins 103:110 Human Milk Proteins 92:110 Human Milk Proteins 92:110 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 36112477 6 8 from glycopeptides 583:595 arg1 digests 612:618 proteolytic digests 600:618 proteolytic digests of human milk 600:632 Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. 36112477 8 9 theme glycopeptide 979:990 arg1 peak 997:1000 each glycopeptide GADS peak 974:1000 each glycopeptide GADS peak 974:1000 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 10 10 theme MS_Piano 1260:1267 arg1 software 1299:1306 MS_Piano, recently reported annotation software 1260:1306 MS_Piano, recently reported annotation software 1260:1306 Spectra are annotated using MS_Piano, recently reported annotation software. 36112477 0 11 theme Human 92:96 arg1 Proteins 103:110 Human Milk Proteins 92:110 Human Milk Proteins 92:110 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 36112477 9 12 theme collision 1159:1167 arg1 fragmentation 1182:1194 higher-energy (stepped) collision dissociation fragmentation 1135:1194 higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation 1135:1229 These were acquired by higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation. 36112477 4 13 theme glycopeptide 428:439 arg1 spectra 464:470 glycopeptide abundance distribution spectra 428:470 glycopeptide abundance distribution spectra (GADS) 428:477 One contains glycopeptide abundance distribution spectra (GADS). 36112477 4 13 theme glycopeptide 428:439 arg1 GADS 473:476 GADS 473:476 GADS 473:476 One contains glycopeptide abundance distribution spectra (GADS). 36112477 7 14 theme GADS 829:832 arg1 library 834:840 a GADS library 827:840 a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins 827:945 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 2 15 theme human 334:338 arg1 glycoproteins 345:357 human milk glycoproteins 334:357 human milk glycoproteins 334:357 Its operation and utility are illustrated by applying it to both newly measured and available proteomics data of human milk glycoproteins. 36112477 1 16 link N-linked 189:196 arg1 glycosylation 206:218 site-specific N-linked protein glycosylation 175:218 site-specific N-linked protein glycosylation 175:218 We present a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation. 36112477 7 17 theme individual 927:936 arg1 proteins 938:945 individual proteins 927:945 individual proteins 927:945 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 7 18 theme milk 776:779 arg1 SRM 810:812 SRM 810:812 SRM 810:812 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 7 18 theme milk 776:779 arg1 material 800:807 a NIST human milk standard reference material 763:807 a NIST human milk standard reference material (SRM) 763:813 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 8 19 gly glycopeptide 979:990 arg2 glycopeptide 979:990 each glycopeptide GADS peak 974:1000 each glycopeptide GADS peak 974:1000 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 11 20 theme accessible 1408:1417 arg1 libraries 1433:1441 accessible mass spectral libraries 1408:1441 accessible mass spectral libraries 1408:1441 This data, with extensions of a widely used spectral library search and display software, provides accessible mass spectral libraries. 36112477 11 21 dep library 1362:1368 arg1 display 1381:1387 display 1381:1387 display software 1381:1396 This data, with extensions of a widely used spectral library search and display software, provides accessible mass spectral libraries. 36112477 11 21 dep library 1362:1368 arg1 search 1370:1375 search 1370:1375 search 1370:1375 This data, with extensions of a widely used spectral library search and display software, provides accessible mass spectral libraries. 36112477 6 22 theme human 623:627 arg1 milk 629:632 human milk 623:632 human milk 623:632 Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. 36112477 0 23 theme Mass 0:3 arg1 Methods 22:28 Mass Spectral Library Methods 0:28 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 0:111 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 36112477 6 24 theme milk 629:632 arg1 digests 612:618 proteolytic digests 600:618 proteolytic digests of human milk 600:632 Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. 36112477 1 25 theme site-specific 175:187 arg1 glycosylation 206:218 site-specific N-linked protein glycosylation 175:218 site-specific N-linked protein glycosylation 175:218 We present a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation. 36112477 0 26 theme Spectral 5:12 arg1 Methods 22:28 Mass Spectral Library Methods 0:28 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 0:111 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 36112477 8 27 theme spectra 1103:1109 arg1 spectra 1064:1070 spectra 1064:1070 spectra of the underlying glycopeptide spectra 1064:1109 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 8 28 theme second 1027:1032 arg1 type 1034:1037 a second type 1025:1037 a second type of library that contains spectra of the underlying glycopeptide spectra 1025:1109 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 5 29 theme underlying 526:535 arg1 glycopeptides 537:549 the underlying glycopeptides 522:549 the underlying glycopeptides 522:549 The other contains tandem mass spectra of the underlying glycopeptides. 36112477 1 30 theme N-linked 189:196 arg1 glycosylation 206:218 site-specific N-linked protein glycosylation 175:218 site-specific N-linked protein glycosylation 175:218 We present a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation. 36112477 3 31 theme libraries 404:412 arg1 libraries 404:412 mass spectral libraries 390:412 mass spectral libraries 390:412 It generates two varieties of mass spectral libraries. 36112477 3 31 theme libraries 404:412 arg1 varieties 377:385 two varieties 373:385 two varieties of mass spectral libraries 373:412 It generates two varieties of mass spectral libraries. 36112477 8 32 theme glycopeptide 1090:1101 arg1 spectra 1103:1109 the underlying glycopeptide spectra 1075:1109 the underlying glycopeptide spectra 1075:1109 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 8 33 theme library 1042:1048 arg1 type 1034:1037 a second type 1025:1037 a second type of library that contains spectra of the underlying glycopeptide spectra 1025:1109 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 6 34 gly glycoproteins 647:659 arg1 glycoproteins 647:659 purified glycoproteins 638:659 purified glycoproteins 638:659 Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. 36112477 6 35 theme several 703:709 arg1 antibodies 711:720 several antibodies 703:720 several antibodies 703:720 Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. 36112477 1 36 theme protein 198:204 arg1 glycosylation 206:218 site-specific N-linked protein glycosylation 175:218 site-specific N-linked protein glycosylation 175:218 We present a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation. 36112477 2 37 theme proteomics 315:324 arg1 data 326:329 available proteomics data 305:329 available proteomics data 305:329 Its operation and utility are illustrated by applying it to both newly measured and available proteomics data of human milk glycoproteins. 36112477 7 38 theme N-glycopeptides 845:859 arg1 library 834:840 a GADS library 827:840 a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins 827:945 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 3 39 theme mass 390:393 arg1 libraries 404:412 mass spectral libraries 390:412 mass spectral libraries 390:412 It generates two varieties of mass spectral libraries. 36112477 8 40 theme underlying 1079:1088 arg1 spectra 1103:1109 the underlying glycopeptide spectra 1075:1109 the underlying glycopeptide spectra 1075:1109 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 10 41 dep MS_Piano 1260:1267 arg1 reported 1279:1286 reported 1279:1286 reported 1279:1286 Spectra are annotated using MS_Piano, recently reported annotation software. 36112477 2 42 theme available 305:313 arg1 data 326:329 available proteomics data 305:329 available proteomics data 305:329 Its operation and utility are illustrated by applying it to both newly measured and available proteomics data of human milk glycoproteins. 36112477 5 43 theme tandem 499:504 arg1 spectra 511:517 tandem mass spectra 499:517 tandem mass spectra of the underlying glycopeptides 499:549 The other contains tandem mass spectra of the underlying glycopeptides. 36112477 11 44 theme library 1362:1368 arg1 extensions 1325:1334 extensions 1325:1334 extensions of a widely used spectral library search and display software 1325:1396 This data, with extensions of a widely used spectral library search and display software, provides accessible mass spectral libraries. 36112477 4 45 contain contains 419:426 arg1 One 415:417 One 415:417 One 415:417 One contains glycopeptide abundance distribution spectra (GADS). 36112477 4 45 contain contains 419:426 arg2 GADS 473:476 GADS 473:476 GADS 473:476 One contains glycopeptide abundance distribution spectra (GADS). 36112477 4 45 contain contains 419:426 arg2 spectra 464:470 glycopeptide abundance distribution spectra 428:470 glycopeptide abundance distribution spectra (GADS) 428:477 One contains glycopeptide abundance distribution spectra (GADS). 36112477 7 46 theme direct 875:880 arg1 comparison 882:891 the direct comparison 871:891 the direct comparison of glycopeptide distributions for individual proteins 871:945 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 7 47 gly glycopeptide 896:907 arg2 glycopeptide 896:907 glycopeptide distributions 896:921 glycopeptide distributions for individual proteins 896:945 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 5 48 theme mass 506:509 arg1 spectra 511:517 tandem mass spectra 499:517 tandem mass spectra of the underlying glycopeptides 499:549 The other contains tandem mass spectra of the underlying glycopeptides. 36112477 11 49 theme spectral 1424:1431 arg1 libraries 1433:1441 accessible mass spectral libraries 1408:1441 accessible mass spectral libraries 1408:1441 This data, with extensions of a widely used spectral library search and display software, provides accessible mass spectral libraries. 36112477 7 50 theme NIST 765:768 arg1 SRM 810:812 SRM 810:812 SRM 810:812 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 7 50 theme NIST 765:768 arg1 material 800:807 a NIST human milk standard reference material 763:807 a NIST human milk standard reference material (SRM) 763:813 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 6 51 from glycoproteins 647:659 arg1 digests 612:618 proteolytic digests 600:618 proteolytic digests of human milk 600:632 Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. 36112477 8 52 contain contains 1055:1062 arg1 type 1034:1037 a second type 1025:1037 a second type of library that contains spectra of the underlying glycopeptide spectra 1025:1109 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 8 52 contain contains 1055:1062 arg2 spectra 1064:1070 spectra 1064:1070 spectra of the underlying glycopeptide spectra 1064:1109 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 0 53 theme Site-Specific 46:58 arg1 N-Glycosylation 60:74 Site-Specific N-Glycosylation 46:74 Site-Specific N-Glycosylation 46:74 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 36112477 5 54 gly glycopeptides 537:549 arg2 glycopeptides 537:549 the underlying glycopeptides 522:549 the underlying glycopeptides 522:549 The other contains tandem mass spectra of the underlying glycopeptides. 36112477 2 55 gly glycoproteins 345:357 arg1 glycoproteins 345:357 human milk glycoproteins 334:357 human milk glycoproteins 334:357 Its operation and utility are illustrated by applying it to both newly measured and available proteomics data of human milk glycoproteins. 36112477 8 56 theme Tandem 948:953 arg1 spectra 955:961 Tandem spectra 948:961 Tandem spectra underlying each glycopeptide GADS peak 948:1000 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 6 57 theme proteolytic 600:610 arg1 digests 612:618 proteolytic digests 600:618 proteolytic digests of human milk 600:632 Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. 36112477 7 58 theme material 800:807 arg1 digests 752:758 digests 752:758 digests of a NIST human milk standard reference material (SRM) 752:813 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 4 59 theme distribution 451:462 arg1 spectra 464:470 glycopeptide abundance distribution spectra 428:470 glycopeptide abundance distribution spectra (GADS) 428:477 One contains glycopeptide abundance distribution spectra (GADS). 36112477 4 59 theme distribution 451:462 arg1 GADS 473:476 GADS 473:476 GADS 473:476 One contains glycopeptide abundance distribution spectra (GADS). 36112477 9 60 theme dissociation 1169:1180 arg1 fragmentation 1182:1194 higher-energy (stepped) collision dissociation fragmentation 1135:1194 higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation 1135:1229 These were acquired by higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation. 36112477 11 61 theme mass 1419:1422 arg1 libraries 1433:1441 accessible mass spectral libraries 1408:1441 accessible mass spectral libraries 1408:1441 This data, with extensions of a widely used spectral library search and display software, provides accessible mass spectral libraries. 36112477 4 62 theme abundance 441:449 arg1 spectra 464:470 glycopeptide abundance distribution spectra 428:470 glycopeptide abundance distribution spectra (GADS) 428:477 One contains glycopeptide abundance distribution spectra (GADS). 36112477 4 62 theme abundance 441:449 arg1 GADS 473:476 GADS 473:476 GADS 473:476 One contains glycopeptide abundance distribution spectra (GADS). 36112477 0 63 dep Methods 22:28 arg1 Application 77:87 Application 77:87 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 0:111 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 36112477 2 64 theme milk 340:343 arg1 glycoproteins 345:357 human milk glycoproteins 334:357 human milk glycoproteins 334:357 Its operation and utility are illustrated by applying it to both newly measured and available proteomics data of human milk glycoproteins. 36112477 5 65 contain contains 490:497 arg1 other 484:488 other 484:488 other 484:488 The other contains tandem mass spectra of the underlying glycopeptides. 36112477 5 65 contain contains 490:497 arg2 spectra 511:517 tandem mass spectra 499:517 tandem mass spectra of the underlying glycopeptides 499:549 The other contains tandem mass spectra of the underlying glycopeptides. 36112477 7 66 theme standard 781:788 arg1 SRM 810:812 SRM 810:812 SRM 810:812 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 7 66 theme standard 781:788 arg1 material 800:807 a NIST human milk standard reference material 763:807 a NIST human milk standard reference material (SRM) 763:813 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 5 67 theme glycopeptides 537:549 arg1 spectra 511:517 tandem mass spectra 499:517 tandem mass spectra of the underlying glycopeptides 499:549 The other contains tandem mass spectra of the underlying glycopeptides. 36112477 1 68 theme mass 126:129 arg1 method 154:159 a mass spectral library-based method 124:159 a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation 124:218 We present a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation. 36112477 10 69 theme annotation 1288:1297 arg1 software 1299:1306 MS_Piano, recently reported annotation software 1260:1306 MS_Piano, recently reported annotation software 1260:1306 Spectra are annotated using MS_Piano, recently reported annotation software. 36112477 7 70 theme reference 790:798 arg1 SRM 810:812 SRM 810:812 SRM 810:812 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 7 70 theme reference 790:798 arg1 material 800:807 a NIST human milk standard reference material 763:807 a NIST human milk standard reference material (SRM) 763:813 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 8 71 theme GADS 992:995 arg1 peak 997:1000 each glycopeptide GADS peak 974:1000 each glycopeptide GADS peak 974:1000 Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. 36112477 11 72 theme spectral 1353:1360 arg1 library 1362:1368 a widely used spectral library 1339:1368 a widely used spectral library search and display software 1339:1396 This data, with extensions of a widely used spectral library search and display software, provides accessible mass spectral libraries. 36112477 6 73 theme purified 638:645 arg1 glycoproteins 647:659 purified glycoproteins 638:659 purified glycoproteins 638:659 Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. 36112477 1 74 theme spectral 131:138 arg1 method 154:159 a mass spectral library-based method 124:159 a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation 124:218 We present a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation. 36112477 3 75 theme spectral 395:402 arg1 libraries 404:412 mass spectral libraries 390:412 mass spectral libraries 390:412 It generates two varieties of mass spectral libraries. 36112477 7 76 theme human 770:774 arg1 SRM 810:812 SRM 810:812 SRM 810:812 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 7 76 theme human 770:774 arg1 material 800:807 a NIST human milk standard reference material 763:807 a NIST human milk standard reference material (SRM) 763:813 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 0 77 theme N-Glycosylation 60:74 arg1 Analysis 34:41 Analysis 34:41 Analysis of Site-Specific N-Glycosylation 34:74 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 36112477 7 78 gly N-glycopeptides 845:859 arg2 N-glycopeptides 845:859 N-glycopeptides 845:859 N-glycopeptides 845:859 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 0 79 theme Library 14:20 arg1 Methods 22:28 Mass Spectral Library Methods 0:28 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 0:111 Mass Spectral Library Methods for Analysis of Site-Specific N-Glycosylation: Application to Human Milk Proteins. 36112477 9 80 theme ion-trap 1208:1215 arg1 fragmentation 1217:1229 ion-trap fragmentation 1208:1229 ion-trap fragmentation 1208:1229 These were acquired by higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation. 36112477 1 81 theme library-based 140:152 arg1 method 154:159 a mass spectral library-based method 124:159 a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation 124:218 We present a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation. 36112477 7 82 theme glycopeptide 896:907 arg1 distributions 909:921 glycopeptide distributions 896:921 glycopeptide distributions for individual proteins 896:945 Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. 36112477 4 83 gly glycopeptide 428:439 arg2 glycopeptide 428:439 glycopeptide abundance distribution spectra 428:470 glycopeptide abundance distribution spectra (GADS) 428:477 One contains glycopeptide abundance distribution spectra (GADS). 35797380 12 0 from teleosts 2125:2132 arg1 foundation 2078:2087 a foundation 2076:2087 a foundation of co-evolution of Lepa and Lepr in teleosts 2076:2132 However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts. 35797380 3 1 theme Lep-Lepr 676:683 arg1 interaction 685:695 Lep-Lepr interaction 676:695 Lep-Lepr interaction 676:695 Conversely, residues predicted essential for Lep-Lepr interaction displayed divergence between teleosts and tetrapods. 35797380 1 2 theme Channa 210:215 arg1 punctata 217:224 spotted snakehead Channa punctata 192:224 spotted snakehead Channa punctata 192:224 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 9 3 theme order 1697:1701 arg1 Anabantiformes 1703:1716 order Anabantiformes 1697:1716 order Anabantiformes 1697:1716 Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. 35797380 6 4 theme C. 1292:1293 arg1 punctata 1295:1302 C. punctata 1292:1302 C. punctata 1292:1302 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 2 5 theme structural 585:594 arg1 integrity 596:604 structural integrity 585:604 structural integrity 585:604 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 6 6 theme nature 1232:1237 arg1 existence 1252:1260 its hydrophobic nature conjecturing existence 1216:1260 its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata 1216:1302 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 5 7 theme Physicochemical 903:917 arg1 properties 919:928 Physicochemical properties 903:928 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates 903:995 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. 35797380 12 8 from co-evolution 2092:2103 arg1 teleosts 2125:2132 teleosts 2125:2132 teleosts 2125:2132 However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts. 35797380 2 9 theme responsible 569:579 arg1 domains 536:542 conserved structural and functional domains 500:542 conserved structural and functional domains 500:542 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 2 9 theme responsible 569:579 arg1 residues 560:567 the residues 556:567 the residues responsible for structural integrity and signal transduction 556:628 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 1 10 theme several 418:424 arg1 species 431:437 several fish species 418:437 several fish species 418:437 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 6 11 theme Lepa 1202:1205 arg1 score 1193:1197 hydropathy score 1182:1197 hydropathy score of Lepa 1182:1205 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 12 12 theme episodic 2039:2046 arg1 selection 2061:2069 pervasive and episodic diversifying selection 2025:2069 pervasive and episodic diversifying selection 2025:2069 However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts. 35797380 2 13 theme C. 481:482 arg1 punctata 484:491 C. punctata 481:491 C. punctata 481:491 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 8 14 theme WSXWS 1508:1512 arg1 motif 1514:1518 WSXWS motif 1508:1518 WSXWS motif in ECD 1508:1525 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 5 15 theme ex 1136:1137 arg1 conditions 1144:1153 ex vivo conditions 1136:1153 ex vivo conditions 1136:1153 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. 35797380 12 16 theme selection 2061:2069 arg1 evidence 2013:2020 evidence 2013:2020 evidence of pervasive and episodic diversifying selection 2013:2069 However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts. 35797380 2 17 theme functional 525:534 arg1 domains 536:542 conserved structural and functional domains 500:542 conserved structural and functional domains 500:542 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 2 17 theme functional 525:534 arg1 residues 560:567 the residues 556:567 the residues responsible for structural integrity and signal transduction 556:628 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 7 18 theme punctata 1431:1438 arg1 Lepa 1420:1423 Lepa 1420:1423 Lepa of C. punctata 1420:1438 In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. 35797380 11 19 theme negative 1895:1902 arg1 selection 1904:1912 negative selection 1895:1912 negative selection 1895:1912 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 2 20 theme structural 510:519 arg1 domains 536:542 conserved structural and functional domains 500:542 conserved structural and functional domains 500:542 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 2 20 theme structural 510:519 arg1 residues 560:567 the residues 556:567 the residues responsible for structural integrity and signal transduction 556:628 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 6 21 theme proteins 1280:1287 arg1 existence 1252:1260 its hydrophobic nature conjecturing existence 1216:1260 its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata 1216:1302 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 2 22 theme putative 444:451 arg1 Lep 465:467 The putative full-length Lep 440:467 The putative full-length Lep 440:467 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 6 23 theme leptin 1265:1270 arg1 proteins 1280:1287 leptin binding proteins 1265:1287 leptin binding proteins in C. punctata 1265:1302 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 6 24 from punctata 1295:1302 arg1 existence 1252:1260 its hydrophobic nature conjecturing existence 1216:1260 its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata 1216:1302 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 8 25 gly glycosylation 1489:1501 arg1 residues 1560:1567 tyrosine residues 1551:1567 tyrosine residues in ICD 1551:1574 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 8 25 gly glycosylation 1489:1501 arg2 residues 1560:1567 tyrosine residues 1551:1567 tyrosine residues in ICD 1551:1574 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 8 25 gly glycosylation 1489:1501 arg1 Lepr 1444:1447 Lepr 1444:1447 Lepr 1444:1447 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 1 26 theme molecular 121:129 arg1 characterization 131:146 molecular characterization 121:146 molecular characterization of leptin (lepa) and its receptor (lepr) 121:187 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 8 27 theme tyrosine 1551:1558 arg1 residues 1560:1567 tyrosine residues 1551:1567 tyrosine residues in ICD 1551:1574 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 11 28 theme pressure 1850:1857 arg1 analysis 1859:1866 Selection pressure analysis 1840:1866 Selection pressure analysis 1840:1866 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 0 29 theme snakehead 60:68 arg1 punctata 77:84 spotted snakehead Channa punctata 52:84 spotted snakehead Channa punctata 52:84 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata. 35797380 1 30 theme pressure 298:305 arg1 analyses 307:314 physicochemical, structural, evolutionary and selection pressure analyses 242:314 physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species 242:437 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 6 31 theme binding 1272:1278 arg1 proteins 1280:1287 leptin binding proteins 1265:1287 leptin binding proteins in C. punctata 1265:1302 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 2 32 theme signal 610:615 arg1 transduction 617:628 signal transduction 610:628 signal transduction 610:628 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 1 33 theme present 91:97 arg1 study 99:103 The present study 87:103 The present study 87:103 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 0 34 theme punctata 77:84 arg1 analyses 10:17 In silico analyses 0:17 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata 0:84 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata. 35797380 11 35 theme higher 1875:1880 arg1 incidence 1882:1890 higher incidence 1875:1890 higher incidence of negative selection in teleostean leptin genes 1875:1939 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 0 36 theme In 0:1 arg1 analyses 10:17 In silico analyses 0:17 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata 0:84 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata. 35797380 9 37 theme C. 1628:1629 arg1 punctata 1631:1638 C. punctata 1628:1638 C. punctata 1628:1638 Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. 35797380 5 38 theme high 1006:1009 arg1 aliphatic 1011:1019 high aliphatic and instability indices 1006:1043 aliphatic 1011:1019 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. 35797380 8 39 theme disulphide 1450:1459 arg1 formation 1466:1474 disulphide bond formation 1450:1474 disulphide bond formation 1450:1474 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 10 40 theme Leptin 1719:1724 arg1 system 1726:1731 Leptin system 1719:1731 Leptin system of Anabantiformes 1719:1749 Leptin system of Anabantiformes was phylogenetically closer to that of Pleuronectiformes, Scombriformes and Perciformes. 35797380 0 41 theme leptin 22:27 arg1 analyses 10:17 In silico analyses 0:17 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata 0:84 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata. 35797380 4 42 theme species 851:857 arg1 specificity 859:869 species specificity 851:869 species specificity in ligand-receptor interaction 851:900 Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. 35797380 0 43 theme leptin 33:38 arg1 receptor 40:47 leptin receptor 33:47 leptin receptor 33:47 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata. 35797380 6 44 theme hydropathy 1182:1191 arg1 score 1193:1197 hydropathy score 1182:1197 hydropathy score of Lepa 1182:1205 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 8 45 theme N-linked 1480:1487 arg1 glycosylation 1489:1501 N-linked glycosylation 1480:1501 N-linked glycosylation 1480:1501 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 11 46 theme leptin 1928:1933 arg1 genes 1935:1939 teleostean leptin genes 1917:1939 teleostean leptin genes 1917:1939 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 4 47 theme effect 818:823 arg1 tool 834:837 protein variation effect analyser tool 800:837 protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction 800:900 Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. 35797380 12 48 theme Lepr 2117:2120 arg1 co-evolution 2092:2103 co-evolution 2092:2103 co-evolution of Lepa and Lepr in teleosts 2092:2132 However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts. 35797380 0 49 dep In 0:1 arg1 silico 3:8 silico 3:8 silico 3:8 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata. 35797380 6 50 theme Positive 1156:1163 arg1 average 1171:1177 Positive grand average 1156:1177 Positive grand average of hydropathy score of Lepa 1156:1205 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 8 51 from motif 1514:1518 arg1 ECD 1523:1525 ECD 1523:1525 ECD 1523:1525 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 1 52 theme snakehead 200:208 arg1 punctata 217:224 spotted snakehead Channa punctata 192:224 spotted snakehead Channa punctata 192:224 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 11 53 from incidence 1882:1890 arg1 genes 1935:1939 teleostean leptin genes 1917:1939 teleostean leptin genes 1917:1939 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 1 54 theme genes 392:396 arg1 existence 373:381 existence 373:381 existence of these genes 373:396 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 1 55 theme punctata 217:224 arg1 characterization 131:146 molecular characterization 121:146 molecular characterization of leptin (lepa) and its receptor (lepr) 121:187 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 12 56 theme co-evolution 2092:2103 arg1 foundation 2078:2087 a foundation 2076:2087 a foundation of co-evolution of Lepa and Lepr in teleosts 2076:2132 However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts. 35797380 6 57 theme conjecturing 1239:1250 arg1 existence 1252:1260 its hydrophobic nature conjecturing existence 1216:1260 its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata 1216:1302 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 1 58 theme leptin 151:156 arg1 characterization 131:146 molecular characterization 121:146 molecular characterization of leptin (lepa) and its receptor (lepr) 121:187 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 12 59 theme Lepa 2108:2111 arg1 co-evolution 2092:2103 co-evolution 2092:2103 co-evolution of Lepa and Lepr in teleosts 2092:2132 However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts. 35797380 6 60 theme hydrophobic 1220:1230 arg1 existence 1252:1260 its hydrophobic nature conjecturing existence 1216:1260 its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata 1216:1302 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 4 61 theme ligand-receptor 874:888 arg1 interaction 890:900 ligand-receptor interaction 874:900 ligand-receptor interaction 874:900 Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. 35797380 1 62 theme fish 426:429 arg1 species 431:437 several fish species 418:437 several fish species 418:437 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 2 63 theme punctata 484:491 arg1 Lep 465:467 The putative full-length Lep 440:467 The putative full-length Lep 440:467 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 2 63 theme punctata 484:491 arg1 Lepr 473:476 Lepr 473:476 Lepr 473:476 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 7 64 theme novel 1342:1346 arg1 modification 1366:1377 a novel posttranslational modification 1340:1377 a novel posttranslational modification (S-126 phosphorylation) 1340:1401 In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. 35797380 7 64 theme novel 1342:1346 arg1 phosphorylation 1386:1400 S-126 phosphorylation 1380:1400 S-126 phosphorylation 1380:1400 In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. 35797380 1 65 theme receptor 173:180 arg1 characterization 131:146 molecular characterization 121:146 molecular characterization of leptin (lepa) and its receptor (lepr) 121:187 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 11 66 theme teleostean 1917:1926 arg1 genes 1935:1939 teleostean leptin genes 1917:1939 teleostean leptin genes 1917:1939 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 12 67 theme diversifying 2048:2059 arg1 selection 2061:2069 pervasive and episodic diversifying selection 2025:2069 pervasive and episodic diversifying selection 2025:2069 However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts. 35797380 9 68 from argus 1688:1692 arg1 homolog 1657:1663 its homolog 1653:1663 its homolog from C. striata and C. argus of order Anabantiformes 1653:1716 Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. 35797380 11 69 theme selection 1904:1912 arg1 incidence 1882:1890 higher incidence 1875:1890 higher incidence of negative selection in teleostean leptin genes 1875:1939 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 5 70 theme proteins 1099:1106 arg1 thermostability 1080:1094 thermostability 1080:1094 thermostability of proteins 1080:1106 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. 35797380 5 71 theme first 971:975 arg1 time 977:980 the first time 967:980 the first time in vertebrates 967:995 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. 35797380 2 72 theme conserved 500:508 arg1 domains 536:542 conserved structural and functional domains 500:542 conserved structural and functional domains 500:542 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 2 72 theme conserved 500:508 arg1 residues 560:567 the residues 556:567 the residues responsible for structural integrity and signal transduction 556:628 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 7 73 theme C. 1428:1429 arg1 punctata 1431:1438 C. punctata 1428:1438 C. punctata 1428:1438 In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. 35797380 4 74 theme protein 800:806 arg1 tool 834:837 protein variation effect analyser tool 800:837 protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction 800:900 Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. 35797380 0 75 theme spotted 52:58 arg1 punctata 77:84 spotted snakehead Channa punctata 52:84 spotted snakehead Channa punctata 52:84 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata. 35797380 5 76 theme ligand 933:938 arg1 properties 919:928 Physicochemical properties 903:928 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates 903:995 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. 35797380 0 77 theme Channa 70:75 arg1 punctata 77:84 spotted snakehead Channa punctata 52:84 spotted snakehead Channa punctata 52:84 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata. 35797380 1 78 theme selection 288:296 arg1 pressure 298:305 selection pressure 288:305 selection pressure 288:305 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 5 79 theme receptor 944:951 arg1 properties 919:928 Physicochemical properties 903:928 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates 903:995 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. 35797380 11 80 from adaptation 1960:1969 arg1 function 1994:2001 function 1994:2001 function 1994:2001 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 11 80 from adaptation 1960:1969 arg1 structure 1980:1988 structure 1980:1988 structure 1980:1988 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 6 81 from proteins 1280:1287 arg1 punctata 1295:1302 C. punctata 1292:1302 C. punctata 1292:1302 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 12 82 theme pervasive 2025:2033 arg1 selection 2061:2069 pervasive and episodic diversifying selection 2025:2069 pervasive and episodic diversifying selection 2025:2069 However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts. 35797380 7 83 dep bonding 1331:1337 arg1 addition 1308:1315 addition 1308:1315 addition 1308:1315 In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. 35797380 8 84 link N-linked 1480:1487 arg1 glycosylation 1489:1501 N-linked glycosylation 1480:1501 N-linked glycosylation 1480:1501 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 10 85 theme Anabantiformes 1736:1749 arg1 system 1726:1731 Leptin system 1719:1731 Leptin system of Anabantiformes 1719:1749 Leptin system of Anabantiformes was phylogenetically closer to that of Pleuronectiformes, Scombriformes and Perciformes. 35797380 5 86 theme instability 1025:1035 arg1 indices 1037:1043 high aliphatic and instability indices 1006:1043 indices 1037:1043 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. 35797380 2 87 theme full-length 453:463 arg1 Lep 465:467 The putative full-length Lep 440:467 The putative full-length Lep 440:467 The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. 35797380 4 88 theme substitutions/deletions 760:782 arg1 Impact 750:755 Impact 750:755 Impact of substitutions/deletions 750:782 Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. 35797380 6 89 from existence 1252:1260 arg1 punctata 1295:1302 C. punctata 1292:1302 C. punctata 1292:1302 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 4 90 from specificity 859:869 arg1 interaction 890:900 ligand-receptor interaction 874:900 ligand-receptor interaction 874:900 Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. 35797380 5 91 from time 977:980 arg1 vertebrates 985:995 vertebrates 985:995 vertebrates 985:995 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. 35797380 9 92 from striata 1673:1679 arg1 homolog 1657:1663 its homolog 1653:1663 its homolog from C. striata and C. argus of order Anabantiformes 1653:1716 Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. 35797380 8 93 from residues 1560:1567 arg1 ICD 1572:1574 ICD 1572:1574 ICD 1572:1574 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 8 93 from residues 1560:1567 arg1 phosphorylation 1532:1546 phosphorylation 1532:1546 phosphorylation at tyrosine residues in ICD 1532:1574 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 8 93 from residues 1560:1567 arg1 formation 1466:1474 disulphide bond formation 1450:1474 disulphide bond formation 1450:1474 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 8 93 from residues 1560:1567 arg1 glycosylation 1489:1501 N-linked glycosylation 1480:1501 N-linked glycosylation 1480:1501 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 9 94 theme punctata 1631:1638 arg1 sequence 1616:1623 its receptor sequence 1603:1623 its receptor sequence of C. punctata 1603:1638 Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. 35797380 9 94 theme punctata 1631:1638 arg1 Leptin 1592:1597 Leptin 1592:1597 Leptin 1592:1597 Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. 35797380 9 95 theme receptor 1607:1614 arg1 sequence 1616:1623 its receptor sequence 1603:1623 its receptor sequence of C. punctata 1603:1638 Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. 35797380 1 96 theme physicochemical 242:256 arg1 analyses 307:314 physicochemical, structural, evolutionary and selection pressure analyses 242:314 physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species 242:437 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 12 97 from foundation 2078:2087 arg1 teleosts 2125:2132 teleosts 2125:2132 teleosts 2125:2132 However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts. 35797380 7 98 theme posttranslational 1348:1364 arg1 modification 1366:1377 a novel posttranslational modification 1340:1377 a novel posttranslational modification (S-126 phosphorylation) 1340:1401 In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. 35797380 7 98 theme posttranslational 1348:1364 arg1 phosphorylation 1386:1400 S-126 phosphorylation 1380:1400 S-126 phosphorylation 1380:1400 In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. 35797380 4 99 theme analyser 825:832 arg1 tool 834:837 protein variation effect analyser tool 800:837 protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction 800:900 Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. 35797380 0 100 theme receptor 40:47 arg1 analyses 10:17 In silico analyses 0:17 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata 0:84 In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata. 35797380 1 101 theme structural 259:268 arg1 analyses 307:314 physicochemical, structural, evolutionary and selection pressure analyses 242:314 physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species 242:437 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 6 102 theme score 1193:1197 arg1 average 1171:1177 Positive grand average 1156:1177 Positive grand average of hydropathy score of Lepa 1156:1205 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 11 103 theme Selection 1840:1848 arg1 analysis 1859:1866 Selection pressure analysis 1840:1866 Selection pressure analysis 1840:1866 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 8 104 theme bond 1461:1464 arg1 formation 1466:1474 disulphide bond formation 1450:1474 disulphide bond formation 1450:1474 In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. 35797380 11 105 theme limited 1952:1958 arg1 adaptation 1960:1969 limited adaptation 1952:1969 limited adaptation in their structure and function 1952:2001 Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. 35797380 1 106 theme evolutionary 271:282 arg1 analyses 307:314 physicochemical, structural, evolutionary and selection pressure analyses 242:314 physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species 242:437 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35797380 9 107 theme C. 1670:1671 arg1 striata 1673:1679 C. striata 1670:1679 C. striata 1670:1679 Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. 35797380 5 108 dep ex 1136:1137 arg1 vivo 1139:1142 vivo 1139:1142 vivo 1139:1142 Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. 35797380 7 109 theme disulphide 1320:1329 arg1 bonding 1331:1337 disulphide bonding 1320:1337 disulphide bonding 1320:1337 In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. 35797380 6 110 theme grand 1165:1169 arg1 average 1171:1177 Positive grand average 1156:1177 Positive grand average of hydropathy score of Lepa 1156:1205 Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. 35797380 4 111 theme variation 808:816 arg1 tool 834:837 protein variation effect analyser tool 800:837 protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction 800:900 Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. 35797380 1 112 theme spotted 192:198 arg1 punctata 217:224 spotted snakehead Channa punctata 192:224 spotted snakehead Channa punctata 192:224 The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. 35734788 5 0 theme rat 794:796 arg1 brain 798:802 rat brain 794:802 rat brain 794:802 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 5 1 with prostate 814:821 arg1 biomolecules 838:849 different biomolecules 828:849 different biomolecules like metabolites and N-linked glycans 828:887 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 1 2 from distributions 196:208 arg1 tissues 240:246 biological tissues 229:246 biological tissues 229:246 Untargeted analyses in mass spectrometry imaging produce hundreds of ion images representing spatial distributions of biomolecules in biological tissues. 35734788 1 3 theme images 168:173 arg1 hundreds 152:159 hundreds 152:159 hundreds of ion images representing spatial distributions of biomolecules in biological tissues 152:246 Untargeted analyses in mass spectrometry imaging produce hundreds of ion images representing spatial distributions of biomolecules in biological tissues. 35734788 6 4 theme increased 950:958 arg1 smoothing 960:968 increased smoothing 950:968 increased smoothing of biological features 950:991 Data transformation by SPC improved ion images resulting in increased smoothing of biological features compared with commonly used normalization approaches. 35734788 5 5 with brain 798:802 arg1 biomolecules 838:849 different biomolecules 828:849 different biomolecules like metabolites and N-linked glycans 828:887 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 4 6 attach present 570:576 arg2 we 567:568 we 567:568 we 567:568 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 4 6 attach present 570:576 arg1 study 560:564 this study 555:564 this study 555:564 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 2 7 theme normalization 317:329 arg1 standards 331:339 normalization standards 317:339 normalization standards 317:339 Due to the large diversity of ions detected in untargeted analyses, normalization standards are often difficult to implement to account for pixel-to-pixel variability in imaging studies. 35734788 3 8 theme Many 436:439 arg1 strategies 455:464 Many normalization strategies 436:464 Many normalization strategies 436:464 Many normalization strategies exist to account for this variability, but they largely do not improve image quality. 35734788 5 9 theme published 760:768 arg1 prostate 814:821 human prostate 808:821 human prostate 808:821 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 5 9 theme published 760:768 arg1 datasets 777:784 previously published tissue datasets 749:784 previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans 749:887 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 5 9 theme published 760:768 arg1 brain 798:802 rat brain 794:802 rat brain 794:802 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 5 10 link N-linked 872:879 arg1 glycans 881:887 N-linked glycans 872:887 N-linked glycans 872:887 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 3 11 theme image 537:541 arg1 quality 543:549 image quality 537:549 image quality 537:549 Many normalization strategies exist to account for this variability, but they largely do not improve image quality. 35734788 4 12 theme image 607:611 arg1 quality 613:619 image quality 607:619 image quality 607:619 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 5 13 theme tissue 770:775 arg1 prostate 814:821 human prostate 808:821 human prostate 808:821 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 5 13 theme tissue 770:775 arg1 datasets 777:784 previously published tissue datasets 749:784 previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans 749:887 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 5 13 theme tissue 770:775 arg1 brain 798:802 rat brain 794:802 rat brain 794:802 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 5 14 theme N-linked 872:879 arg1 glycans 881:887 N-linked glycans 872:887 N-linked glycans 872:887 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 4 15 theme features 649:656 arg1 visualization 625:637 visualization 625:637 visualization of tissue features by application of sequential paired covariance (SPC) 625:709 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 4 15 theme features 649:656 arg1 quality 613:619 image quality 607:619 image quality 607:619 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 2 16 theme untargeted 296:305 arg1 analyses 307:314 untargeted analyses 296:314 untargeted analyses 296:314 Due to the large diversity of ions detected in untargeted analyses, normalization standards are often difficult to implement to account for pixel-to-pixel variability in imaging studies. 35734788 1 17 theme spatial 188:194 arg1 distributions 196:208 spatial distributions 188:208 spatial distributions of biomolecules in biological tissues 188:246 Untargeted analyses in mass spectrometry imaging produce hundreds of ion images representing spatial distributions of biomolecules in biological tissues. 35734788 6 18 theme ion 926:928 arg1 images 930:935 ion images 926:935 ion images resulting in increased smoothing of biological features 926:991 Data transformation by SPC improved ion images resulting in increased smoothing of biological features compared with commonly used normalization approaches. 35734788 5 19 theme different 828:836 arg1 biomolecules 838:849 different biomolecules 828:849 different biomolecules like metabolites and N-linked glycans 828:887 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 4 20 theme sequential 676:685 arg1 SPC 706:708 SPC 706:708 SPC 706:708 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 4 20 theme sequential 676:685 arg1 covariance 694:703 sequential paired covariance 676:703 sequential paired covariance (SPC) 676:709 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 0 21 theme paired 11:16 arg1 covariance 18:27 Sequential paired covariance 0:27 Sequential paired covariance for improved visualization of mass spectrometry 0:75 Sequential paired covariance for improved visualization of mass spectrometry imaging datasets. 35734788 1 22 theme Untargeted 95:104 arg1 analyses 106:113 Untargeted analyses 95:113 Untargeted analyses in mass spectrometry imaging 95:142 Untargeted analyses in mass spectrometry imaging produce hundreds of ion images representing spatial distributions of biomolecules in biological tissues. 35734788 2 23 theme imaging 419:425 arg1 studies 427:433 imaging studies 419:433 imaging studies 419:433 Due to the large diversity of ions detected in untargeted analyses, normalization standards are often difficult to implement to account for pixel-to-pixel variability in imaging studies. 35734788 0 24 theme Sequential 0:9 arg1 covariance 18:27 Sequential paired covariance 0:27 Sequential paired covariance for improved visualization of mass spectrometry 0:75 Sequential paired covariance for improved visualization of mass spectrometry imaging datasets. 35734788 2 25 from variability 404:414 arg1 studies 427:433 imaging studies 419:433 imaging studies 419:433 Due to the large diversity of ions detected in untargeted analyses, normalization standards are often difficult to implement to account for pixel-to-pixel variability in imaging studies. 35734788 1 26 theme biomolecules 213:224 arg1 distributions 196:208 spatial distributions 188:208 spatial distributions of biomolecules in biological tissues 188:246 Untargeted analyses in mass spectrometry imaging produce hundreds of ion images representing spatial distributions of biomolecules in biological tissues. 35734788 6 27 theme normalization 1021:1033 arg1 approaches 1035:1044 commonly used normalization approaches 1007:1044 commonly used normalization approaches 1007:1044 Data transformation by SPC improved ion images resulting in increased smoothing of biological features compared with commonly used normalization approaches. 35734788 6 28 theme used 1016:1019 arg1 approaches 1035:1044 commonly used normalization approaches 1007:1044 commonly used normalization approaches 1007:1044 Data transformation by SPC improved ion images resulting in increased smoothing of biological features compared with commonly used normalization approaches. 35734788 1 29 theme mass 118:121 arg1 spectrometry 123:134 mass spectrometry 118:134 mass spectrometry imaging 118:142 Untargeted analyses in mass spectrometry imaging produce hundreds of ion images representing spatial distributions of biomolecules in biological tissues. 35734788 1 30 theme biological 229:238 arg1 tissues 240:246 biological tissues 229:246 biological tissues 229:246 Untargeted analyses in mass spectrometry imaging produce hundreds of ion images representing spatial distributions of biomolecules in biological tissues. 35734788 4 31 theme new 580:582 arg1 approach 584:591 a new approach 578:591 a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC) 578:709 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 2 32 theme large 260:264 arg1 diversity 266:274 the large diversity 256:274 the large diversity of ions detected in untargeted analyses 256:314 Due to the large diversity of ions detected in untargeted analyses, normalization standards are often difficult to implement to account for pixel-to-pixel variability in imaging studies. 35734788 4 33 theme covariance 694:703 arg1 application 661:671 application 661:671 application of sequential paired covariance (SPC) 661:709 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 0 34 theme improved 33:40 arg1 visualization 42:54 improved visualization 33:54 improved visualization of mass spectrometry 33:75 Sequential paired covariance for improved visualization of mass spectrometry imaging datasets. 35734788 5 35 theme human 808:812 arg1 prostate 814:821 human prostate 808:821 human prostate 808:821 This approach was demonstrated using previously published tissue datasets such as rat brain and human prostate with different biomolecules like metabolites and N-linked glycans. 35734788 0 36 theme mass 59:62 arg1 spectrometry 64:75 mass spectrometry 59:75 mass spectrometry 59:75 Sequential paired covariance for improved visualization of mass spectrometry imaging datasets. 35734788 6 37 theme Data 890:893 arg1 transformation 895:908 Data transformation 890:908 Data transformation by SPC 890:915 Data transformation by SPC improved ion images resulting in increased smoothing of biological features compared with commonly used normalization approaches. 35734788 1 38 theme spectrometry 123:134 arg1 imaging 136:142 mass spectrometry imaging 118:142 mass spectrometry imaging 118:142 Untargeted analyses in mass spectrometry imaging produce hundreds of ion images representing spatial distributions of biomolecules in biological tissues. 35734788 3 39 theme normalization 441:453 arg1 strategies 455:464 Many normalization strategies 436:464 Many normalization strategies 436:464 Many normalization strategies exist to account for this variability, but they largely do not improve image quality. 35734788 6 40 theme features 984:991 arg1 smoothing 960:968 increased smoothing 950:968 increased smoothing of biological features 950:991 Data transformation by SPC improved ion images resulting in increased smoothing of biological features compared with commonly used normalization approaches. 35734788 6 41 theme biological 973:982 arg1 features 984:991 biological features 973:991 biological features 973:991 Data transformation by SPC improved ion images resulting in increased smoothing of biological features compared with commonly used normalization approaches. 35734788 2 42 theme ions 279:282 arg1 diversity 266:274 the large diversity 256:274 the large diversity of ions detected in untargeted analyses 256:314 Due to the large diversity of ions detected in untargeted analyses, normalization standards are often difficult to implement to account for pixel-to-pixel variability in imaging studies. 35734788 1 43 theme ion 164:166 arg1 images 168:173 ion images 164:173 ion images representing spatial distributions of biomolecules in biological tissues 164:246 Untargeted analyses in mass spectrometry imaging produce hundreds of ion images representing spatial distributions of biomolecules in biological tissues. 35734788 2 44 located detected 284:291 arg1 analyses 307:314 untargeted analyses 296:314 untargeted analyses 296:314 Due to the large diversity of ions detected in untargeted analyses, normalization standards are often difficult to implement to account for pixel-to-pixel variability in imaging studies. 35734788 2 44 located detected 284:291 arg2 ions 279:282 ions 279:282 ions detected in untargeted analyses 279:314 Due to the large diversity of ions detected in untargeted analyses, normalization standards are often difficult to implement to account for pixel-to-pixel variability in imaging studies. 35734788 4 45 theme paired 687:692 arg1 SPC 706:708 SPC 706:708 SPC 706:708 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 4 45 theme paired 687:692 arg1 covariance 694:703 sequential paired covariance 676:703 sequential paired covariance (SPC) 676:709 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 1 46 from analyses 106:113 arg1 imaging 136:142 mass spectrometry imaging 118:142 mass spectrometry imaging 118:142 Untargeted analyses in mass spectrometry imaging produce hundreds of ion images representing spatial distributions of biomolecules in biological tissues. 35734788 4 47 theme tissue 642:647 arg1 features 649:656 tissue features 642:656 tissue features 642:656 In this study, we present a new approach for improving image quality and visualization of tissue features by application of sequential paired covariance (SPC). 35734788 0 48 theme spectrometry 64:75 arg1 visualization 42:54 improved visualization 33:54 improved visualization of mass spectrometry 33:75 Sequential paired covariance for improved visualization of mass spectrometry imaging datasets. 35734788 2 49 theme pixel-to-pixel 389:402 arg1 variability 404:414 pixel-to-pixel variability 389:414 pixel-to-pixel variability in imaging studies 389:433 Due to the large diversity of ions detected in untargeted analyses, normalization standards are often difficult to implement to account for pixel-to-pixel variability in imaging studies. 35467485 1 0 link N-linked 296:303 arg1 glycans 305:311 N-linked glycans 296:311 N-linked glycans 296:311 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition is reported to kill tumor cells whose growth progression requires increased branching of N-linked glycans. 35467485 5 1 theme binding 998:1004 arg1 poses 1006:1010 their binding poses 992:1010 their binding poses 992:1010 Analysis of their binding poses identified essential pharmacophores involved in target-ligand complexation that could be targeted in chemical modification to develop more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma. 35467485 5 2 theme essential 1023:1031 arg1 pharmacophores 1033:1046 essential pharmacophores 1023:1046 essential pharmacophores involved in target-ligand complexation that could be targeted in chemical modification to develop more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma 1023:1221 Analysis of their binding poses identified essential pharmacophores involved in target-ligand complexation that could be targeted in chemical modification to develop more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma. 35467485 4 3 theme docking 958:964 arg1 calculations 966:977 docking calculations 958:977 docking calculations 958:977 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 5 4 theme poses 1006:1010 arg1 Analysis 980:987 Analysis 980:987 Analysis of their binding poses 980:1010 Analysis of their binding poses identified essential pharmacophores involved in target-ligand complexation that could be targeted in chemical modification to develop more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma. 35467485 3 5 theme chemotherapeutic 674:689 arg1 inhibitors 634:643 theoretical dpagt1 inhibitors 615:643 theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs 615:695 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 3 5 theme chemotherapeutic 674:689 arg1 drugs 691:695 chemotherapeutic drugs 674:695 chemotherapeutic drugs 674:695 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 4 6 dep structure-based-pharmacophore- 887:916 arg1 calculations 966:977 docking calculations 958:977 docking calculations 958:977 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 4 7 theme Top 698:700 arg1 affinity 739:746 binding affinity 731:746 binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol 731:799 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 4 7 theme Top 698:700 arg1 drugs 724:728 Top six better performing drugs 698:728 Top six better performing drugs 698:728 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 4 8 theme reference 811:819 arg1 ligand 821:826 the reference ligand 807:826 the reference ligand (tunicamycin; -14.86 kcal/mol) 807:857 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 4 9 from range 766:770 arg1 affinity 739:746 binding affinity 731:746 binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol 731:799 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 4 9 from range 766:770 arg1 drugs 724:728 Top six better performing drugs 698:728 Top six better performing drugs 698:728 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 3 10 theme FDA 577:579 arg1 drugs 590:594 ∼1300 FDA approved drugs 571:594 ∼1300 FDA approved drugs 571:594 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 4 11 theme induced 945:951 arg1 fit 953:955 'induced fit' 944:956 'induced fit' 944:956 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 3 12 theme theoretical 615:625 arg1 inhibitors 634:643 theoretical dpagt1 inhibitors 615:643 theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs 615:695 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 3 12 theme theoretical 615:625 arg1 drugs 691:695 chemotherapeutic drugs 674:695 chemotherapeutic drugs 674:695 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 2 13 theme effective 485:493 arg1 inhibitors 502:511 new, safe and effective dpagt1 inhibitors 471:511 new, safe and effective dpagt1 inhibitors 471:511 Available dpagt1 inhibitors are grossly limited and are faced with problems of heamolytic effect and aqueous solubility thereby necessitating the search for new, safe and effective dpagt1 inhibitors. 35467485 1 14 theme Dolichyl-phosphate 130:147 arg1 dpagt1 188:193 dpagt1 188:193 dpagt1 188:193 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition is reported to kill tumor cells whose growth progression requires increased branching of N-linked glycans. 35467485 1 14 theme Dolichyl-phosphate 130:147 arg1 N-acetylglucosaminephosphotransferase 149:185 Dolichyl-phosphate N-acetylglucosaminephosphotransferase 130:185 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition 130:205 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition is reported to kill tumor cells whose growth progression requires increased branching of N-linked glycans. 35467485 5 15 theme effective 1151:1159 arg1 dpagt1 1170:1175 more effective and safe dpagt1 1146:1175 more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma 1146:1221 Analysis of their binding poses identified essential pharmacophores involved in target-ligand complexation that could be targeted in chemical modification to develop more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma. 35467485 1 16 theme N-acetylglucosaminephosphotransferase 149:185 arg1 inhibition 196:205 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition 130:205 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition 130:205 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition is reported to kill tumor cells whose growth progression requires increased branching of N-linked glycans. 35467485 2 17 theme safe 476:479 arg1 inhibitors 502:511 new, safe and effective dpagt1 inhibitors 471:511 new, safe and effective dpagt1 inhibitors 471:511 Available dpagt1 inhibitors are grossly limited and are faced with problems of heamolytic effect and aqueous solubility thereby necessitating the search for new, safe and effective dpagt1 inhibitors. 35467485 0 18 theme Computational 0:12 arg1 studies 14:20 Computational studies 0:20 Computational studies 0:20 Computational studies reveal potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors amidst existing drugs. 35467485 4 19 theme fit 953:955 arg1 end 880:882 the end 876:882 the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations 876:977 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 2 20 theme effect 404:409 arg1 problems 381:388 problems 381:388 problems of heamolytic effect and aqueous solubility 381:432 Available dpagt1 inhibitors are grossly limited and are faced with problems of heamolytic effect and aqueous solubility thereby necessitating the search for new, safe and effective dpagt1 inhibitors. 35467485 1 21 theme increased 273:281 arg1 branching 283:291 increased branching 273:291 increased branching of N-linked glycans 273:311 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition is reported to kill tumor cells whose growth progression requires increased branching of N-linked glycans. 35467485 0 22 theme potential 29:37 arg1 inhibitors 96:105 potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors 29:105 potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors 29:105 Computational studies reveal potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors amidst existing drugs. 35467485 5 23 theme safe 1165:1168 arg1 dpagt1 1170:1175 more effective and safe dpagt1 1146:1175 more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma 1146:1221 Analysis of their binding poses identified essential pharmacophores involved in target-ligand complexation that could be targeted in chemical modification to develop more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma. 35467485 2 24 theme heamolytic 393:402 arg1 effect 404:409 heamolytic effect 393:409 heamolytic effect 393:409 Available dpagt1 inhibitors are grossly limited and are faced with problems of heamolytic effect and aqueous solubility thereby necessitating the search for new, safe and effective dpagt1 inhibitors. 35467485 4 25 theme binding 731:737 arg1 affinity 739:746 binding affinity 731:746 binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol 731:799 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 4 25 theme binding 731:737 arg1 drugs 724:728 Top six better performing drugs 698:728 Top six better performing drugs 698:728 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 5 26 theme target-ligand 1060:1072 arg1 complexation 1074:1085 target-ligand complexation 1060:1085 target-ligand complexation that could be targeted in chemical modification to develop more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma 1060:1221 Analysis of their binding poses identified essential pharmacophores involved in target-ligand complexation that could be targeted in chemical modification to develop more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma. 35467485 4 27 theme -17.63 775:780 arg1 range 766:770 the range 762:770 the range of -17.63 to -20.40 kcal/mol 762:799 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 0 28 theme N-acetylglucosaminephosphotransferase 58:94 arg1 inhibitors 96:105 potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors 29:105 potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors 29:105 Computational studies reveal potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors amidst existing drugs. 35467485 4 29 dep tunicamycin 829:839 arg1 -14.86 kcal/mol 842:856 -14.86 kcal/mol 842:856 tunicamycin; -14.86 kcal/mol 829:856 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 3 30 theme computational 526:538 arg1 methods 540:546 computational methods 526:546 computational methods 526:546 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 1 31 theme N-linked 296:303 arg1 glycans 305:311 N-linked glycans 296:311 N-linked glycans 296:311 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition is reported to kill tumor cells whose growth progression requires increased branching of N-linked glycans. 35467485 1 32 theme growth 245:250 arg1 progression 252:262 progression 252:262 progression 252:262 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition is reported to kill tumor cells whose growth progression requires increased branching of N-linked glycans. 35467485 0 33 theme dolichyl-phosphate 39:56 arg1 inhibitors 96:105 potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors 29:105 potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors 29:105 Computational studies reveal potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors amidst existing drugs. 35467485 2 34 theme dpagt1 324:329 arg1 inhibitors 331:340 Available dpagt1 inhibitors 314:340 Available dpagt1 inhibitors 314:340 Available dpagt1 inhibitors are grossly limited and are faced with problems of heamolytic effect and aqueous solubility thereby necessitating the search for new, safe and effective dpagt1 inhibitors. 35467485 1 35 theme glycans 305:311 arg1 branching 283:291 increased branching 273:291 increased branching of N-linked glycans 273:311 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition is reported to kill tumor cells whose growth progression requires increased branching of N-linked glycans. 35467485 2 36 theme Available 314:322 arg1 inhibitors 331:340 Available dpagt1 inhibitors 314:340 Available dpagt1 inhibitors 314:340 Available dpagt1 inhibitors are grossly limited and are faced with problems of heamolytic effect and aqueous solubility thereby necessitating the search for new, safe and effective dpagt1 inhibitors. 35467485 3 37 theme approved 581:588 arg1 drugs 590:594 ∼1300 FDA approved drugs 571:594 ∼1300 FDA approved drugs 571:594 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 4 38 theme virtual-screening 922:938 arg1 end 880:882 the end 876:882 the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations 876:977 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 3 39 theme drugs 590:594 arg1 dataset 560:566 a dataset 558:566 a dataset of ∼1300 FDA approved drugs 558:594 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 5 40 theme chemical 1113:1120 arg1 modification 1122:1133 chemical modification 1113:1133 chemical modification 1113:1133 Analysis of their binding poses identified essential pharmacophores involved in target-ligand complexation that could be targeted in chemical modification to develop more effective and safe dpagt1 inhibitors.Communicated by Ramaswamy H. Sarma. 35467485 4 41 theme structure-based-pharmacophore- 887:916 arg1 end 880:882 the end 876:882 the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations 876:977 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 2 42 theme solubility 423:432 arg1 problems 381:388 problems 381:388 problems of heamolytic effect and aqueous solubility 381:432 Available dpagt1 inhibitors are grossly limited and are faced with problems of heamolytic effect and aqueous solubility thereby necessitating the search for new, safe and effective dpagt1 inhibitors. 35467485 3 43 theme dpagt1 627:632 arg1 inhibitors 634:643 theoretical dpagt1 inhibitors 615:643 theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs 615:695 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 3 43 theme dpagt1 627:632 arg1 drugs 691:695 chemotherapeutic drugs 674:695 chemotherapeutic drugs 674:695 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 2 44 theme aqueous 415:421 arg1 solubility 423:432 aqueous solubility 415:432 aqueous solubility 415:432 Available dpagt1 inhibitors are grossly limited and are faced with problems of heamolytic effect and aqueous solubility thereby necessitating the search for new, safe and effective dpagt1 inhibitors. 35467485 3 45 theme ∼1300 571:575 arg1 drugs 590:594 ∼1300 FDA approved drugs 571:594 ∼1300 FDA approved drugs 571:594 We employed computational methods to screen a dataset of ∼1300 FDA approved drugs in order to obtain theoretical dpagt1 inhibitors which could be repurposed as chemotherapeutic drugs. 35467485 2 46 theme dpagt1 495:500 arg1 inhibitors 502:511 new, safe and effective dpagt1 inhibitors 471:511 new, safe and effective dpagt1 inhibitors 471:511 Available dpagt1 inhibitors are grossly limited and are faced with problems of heamolytic effect and aqueous solubility thereby necessitating the search for new, safe and effective dpagt1 inhibitors. 35467485 2 47 theme new 471:473 arg1 inhibitors 502:511 new, safe and effective dpagt1 inhibitors 471:511 new, safe and effective dpagt1 inhibitors 471:511 Available dpagt1 inhibitors are grossly limited and are faced with problems of heamolytic effect and aqueous solubility thereby necessitating the search for new, safe and effective dpagt1 inhibitors. 35467485 0 48 theme existing 114:121 arg1 drugs 123:127 existing drugs 114:127 existing drugs 114:127 Computational studies reveal potential dolichyl-phosphate N-acetylglucosaminephosphotransferase inhibitors amidst existing drugs. 35467485 4 49 dep ligand 821:826 arg1 tunicamycin 829:839 tunicamycin 829:839 tunicamycin; -14.86 kcal/mol 829:856 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 1 50 theme tumor 227:231 arg1 cells 233:237 tumor cells 227:237 tumor cells whose growth progression requires increased branching of N-linked glycans 227:311 Dolichyl-phosphate N-acetylglucosaminephosphotransferase (dpagt1) inhibition is reported to kill tumor cells whose growth progression requires increased branching of N-linked glycans. 35467485 4 51 theme performing 713:722 arg1 affinity 739:746 binding affinity 731:746 binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol 731:799 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 35467485 4 51 theme performing 713:722 arg1 drugs 724:728 Top six better performing drugs 698:728 Top six better performing drugs 698:728 Top six better performing drugs, binding affinity for dpagt1 at the range of -17.63 to -20.40 kcal/mol, than the reference ligand (tunicamycin; -14.86 kcal/mol) were obtained at the end of structure-based-pharmacophore- and virtual-screening and 'induced fit' docking calculations. 36687526 6 0 theme network 1068:1074 arg1 members 1076:1082 network members 1068:1082 network members 1068:1082 We validated mRNA expression of network members, and then extended our analysis to older stages. 36687526 5 1 gly glycoproteins 869:881 arg1 SIBLINGs 884:891 SIBLINGs 884:891 SIBLINGs 884:891 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 5 1 gly glycoproteins 869:881 arg1 glycoproteins 869:881 Called small integrin-binding ligand n-linked glycoproteins 823:881 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs) 823:892 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 3 2 theme secreted 700:707 arg1 effectors 709:717 potential secreted effectors 690:717 potential secreted effectors 690:717 Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. 36687526 7 3 theme gene 1204:1207 arg1 members 1217:1223 gene network members 1204:1223 gene network members 1204:1223 ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. 36687526 5 4 from survival 973:980 arg1 systems 1027:1033 other systems 1021:1033 other systems 1021:1033 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 4 5 theme gene 809:812 arg1 network 814:820 a gene network 807:820 a gene network 807:820 ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. 36687526 3 6 from SCs 635:637 arg1 transcriptomes 591:604 single cell transcriptomes 579:604 single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2 579:658 Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. 36687526 5 7 theme small 830:834 arg1 SIBLINGs 884:891 SIBLINGs 884:891 SIBLINGs 884:891 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 5 7 theme small 830:834 arg1 glycoproteins 869:881 Called small integrin-binding ligand n-linked glycoproteins 823:881 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs) 823:892 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 5 8 theme ligand 853:858 arg1 SIBLINGs 884:891 SIBLINGs 884:891 SIBLINGs 884:891 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 5 8 theme ligand 853:858 arg1 glycoproteins 869:881 Called small integrin-binding ligand n-linked glycoproteins 823:881 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs) 823:892 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 10 9 theme mammalian 1569:1577 arg1 cochlea 1579:1585 the adult mammalian cochlea 1559:1585 the adult mammalian cochlea 1559:1585 Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea. 36687526 5 10 from proliferation 983:995 arg1 systems 1027:1033 other systems 1021:1033 other systems 1021:1033 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 4 11 dep de 785:786 arg1 novo 788:791 novo 788:791 novo 788:791 ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. 36687526 2 12 theme cells 556:560 arg1 proliferation 506:518 proliferation 506:518 proliferation 506:518 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 2 12 theme cells 556:560 arg1 down-regulation 460:474 widespread down-regulation 449:474 widespread down-regulation of SOX2 in neighboring cells 449:503 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 2 12 theme cells 556:560 arg1 differentiation 529:543 the differentiation 525:543 the differentiation of HC-like cells 525:560 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 8 13 theme cochlear 1262:1269 arg1 aggregates 1276:1285 proliferating cochlear cell aggregates 1248:1285 proliferating cochlear cell aggregates 1248:1285 Furthermore, we found proliferating cochlear cell aggregates in the organ of Corti. 36687526 2 14 theme SOX2 479:482 arg1 proliferation 506:518 proliferation 506:518 proliferation 506:518 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 2 14 theme SOX2 479:482 arg1 down-regulation 460:474 widespread down-regulation 449:474 widespread down-regulation of SOX2 in neighboring cells 449:503 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 2 14 theme SOX2 479:482 arg1 differentiation 529:543 the differentiation 525:543 the differentiation of HC-like cells 525:560 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 0 15 theme supporting 54:63 arg1 transcriptomes 70:83 mouse cochlear supporting cell transcriptomes 39:83 mouse cochlear supporting cell transcriptomes 39:83 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 7 16 theme ERBB2 1133:1137 arg1 signaling 1139:1147 ERBB2 signaling 1133:1147 ERBB2 signaling in young adult SCs 1133:1166 ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. 36687526 2 17 from activation 401:410 arg1 subset 417:422 a subset 415:422 a subset of cochlear SCs 415:438 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 0 18 theme transcriptomes 70:83 arg1 analysis 27:34 Single cell RNA sequencing analysis 0:34 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor 0:113 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 9 19 from activation 1343:1352 arg1 SCs 1385:1387 cochlear SCs 1376:1387 cochlear SCs 1376:1387 Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. 36687526 0 20 theme activated 90:98 arg1 receptor 106:113 activated ERBB2 receptor 90:113 activated ERBB2 receptor 90:113 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 5 21 theme NOTCH 940:944 arg1 signaling 946:954 NOTCH signaling 940:954 NOTCH signaling 940:954 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 2 22 theme neighboring 487:497 arg1 cells 499:503 neighboring cells 487:503 neighboring cells 487:503 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 4 23 theme new 756:758 arg1 population 760:769 a new population 754:769 a new population of cells with de novo expression of a gene network 754:820 ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. 36687526 7 24 theme adult 1158:1162 arg1 SCs 1164:1166 young adult SCs 1152:1166 young adult SCs 1152:1166 ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. 36687526 6 25 theme mRNA 1049:1052 arg1 expression 1054:1063 mRNA expression 1049:1063 mRNA expression of network members 1049:1082 We validated mRNA expression of network members, and then extended our analysis to older stages. 36687526 4 26 theme ERBB2 720:724 arg1 induction 726:734 ERBB2 induction 720:734 ERBB2 induction in vivo 720:742 ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. 36687526 0 27 theme Single 0:5 arg1 analysis 27:34 Single cell RNA sequencing analysis 0:34 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor 0:113 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 2 28 theme ERBB2 395:399 arg1 activation 401:410 ERBB2 activation 395:410 ERBB2 activation in a subset of cochlear SCs 395:438 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 0 29 theme RNA 12:14 arg1 analysis 27:34 Single cell RNA sequencing analysis 0:34 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor 0:113 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 5 30 theme Called 823:828 arg1 SIBLINGs 884:891 SIBLINGs 884:891 SIBLINGs 884:891 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 5 30 theme Called 823:828 arg1 glycoproteins 869:881 Called small integrin-binding ligand n-linked glycoproteins 823:881 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs) 823:892 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 2 31 theme cochlear 427:434 arg1 SCs 436:438 cochlear SCs 427:438 cochlear SCs 427:438 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 3 32 theme mouse 620:624 arg1 SCs 635:637 neonatal mouse cochlear SCs 611:637 neonatal mouse cochlear SCs with activated ERBB2 611:658 Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. 36687526 0 33 theme mouse 39:43 arg1 transcriptomes 70:83 mouse cochlear supporting cell transcriptomes 39:83 mouse cochlear supporting cell transcriptomes 39:83 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 9 34 theme ectopic 1335:1341 arg1 activation 1343:1352 ectopic activation 1335:1352 ectopic activation of ERBB2 signaling in cochlear SCs 1335:1387 Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. 36687526 3 35 theme cell 586:589 arg1 transcriptomes 591:604 single cell transcriptomes 579:604 single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2 579:658 Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. 36687526 1 36 theme hair 226:229 arg1 HCs 238:240 HCs 238:240 HCs 238:240 Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. 36687526 1 36 theme hair 226:229 arg1 cells 231:235 cochlear hair cells 217:235 cochlear hair cells (HCs) 217:241 Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. 36687526 5 37 theme cell 968:971 arg1 survival 973:980 cell survival 968:980 cell survival 968:980 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 2 38 from proliferation 506:518 arg1 cells 499:503 neighboring cells 487:503 neighboring cells 487:503 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 10 39 theme cell-like 1537:1545 arg1 activity 1547:1554 stem cell-like activity 1532:1554 stem cell-like activity 1532:1554 Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea. 36687526 3 40 theme activated 644:652 arg1 ERBB2 654:658 activated ERBB2 644:658 activated ERBB2 644:658 Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. 36687526 9 41 theme signaling 1363:1371 arg1 activation 1343:1352 ectopic activation 1335:1352 ectopic activation of ERBB2 signaling in cochlear SCs 1335:1387 Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. 36687526 6 42 theme members 1076:1082 arg1 expression 1054:1063 mRNA expression 1049:1063 mRNA expression of network members 1049:1082 We validated mRNA expression of network members, and then extended our analysis to older stages. 36687526 0 43 with analysis 27:34 arg1 receptor 106:113 activated ERBB2 receptor 90:113 activated ERBB2 receptor 90:113 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 9 44 theme cochlear 1376:1383 arg1 SCs 1385:1387 cochlear SCs 1376:1387 cochlear SCs 1376:1387 Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. 36687526 7 45 theme network 1209:1215 arg1 members 1217:1223 gene network members 1204:1223 gene network members 1204:1223 ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. 36687526 2 46 from differentiation 529:543 arg1 cells 499:503 neighboring cells 487:503 neighboring cells 487:503 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 10 47 theme adult 1563:1567 arg1 cochlea 1579:1585 the adult mammalian cochlea 1559:1585 the adult mammalian cochlea 1559:1585 Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea. 36687526 1 48 from cells 298:302 arg1 regeneration 269:280 regeneration 269:280 regeneration from supporting cells (SCs) 269:308 Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. 36687526 1 49 theme Hearing 181:187 arg1 loss 189:192 Hearing loss 181:192 Hearing loss caused by the death of cochlear hair cells (HCs) 181:241 Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. 36687526 3 50 theme potential 690:698 arg1 effectors 709:717 potential secreted effectors 690:717 potential secreted effectors 690:717 Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. 36687526 7 51 theme protein 1182:1188 arg1 expression 1190:1199 protein expression 1182:1199 protein expression of gene network members 1182:1223 ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. 36687526 5 52 theme integrin-binding 836:851 arg1 SIBLINGs 884:891 SIBLINGs 884:891 SIBLINGs 884:891 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 5 52 theme integrin-binding 836:851 arg1 glycoproteins 869:881 Called small integrin-binding ligand n-linked glycoproteins 823:881 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs) 823:892 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 4 53 theme network 814:820 arg1 expression 793:802 de novo expression 785:802 de novo expression of a gene network 785:820 ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. 36687526 6 54 theme older 1119:1123 arg1 stages 1125:1130 older stages 1119:1130 older stages 1119:1130 We validated mRNA expression of network members, and then extended our analysis to older stages. 36687526 0 55 theme cell-specific 127:139 arg1 response 141:148 a cell-specific response 125:148 a cell-specific response that promotes CD44 activation 125:178 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 5 56 from differentiation 1002:1016 arg1 systems 1027:1033 other systems 1021:1033 other systems 1021:1033 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 2 57 from down-regulation 460:474 arg1 cells 499:503 neighboring cells 487:503 neighboring cells 487:503 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 3 58 with SCs 635:637 arg1 ERBB2 654:658 activated ERBB2 644:658 activated ERBB2 644:658 Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. 36687526 9 59 theme cell 1449:1452 arg1 rearrangements 1454:1467 cell rearrangements 1449:1467 cell rearrangements 1449:1467 Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. 36687526 0 60 theme CD44 164:167 arg1 activation 169:178 CD44 activation 164:178 CD44 activation 164:178 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 2 61 theme HC-like 548:554 arg1 cells 556:560 HC-like cells 548:560 HC-like cells 548:560 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 8 62 theme proliferating 1248:1260 arg1 aggregates 1276:1285 proliferating cochlear cell aggregates 1248:1285 proliferating cochlear cell aggregates 1248:1285 Furthermore, we found proliferating cochlear cell aggregates in the organ of Corti. 36687526 5 63 theme other 1021:1025 arg1 systems 1027:1033 other systems 1021:1033 other systems 1021:1033 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 8 64 theme cell 1271:1274 arg1 aggregates 1276:1285 proliferating cochlear cell aggregates 1248:1285 proliferating cochlear cell aggregates 1248:1285 Furthermore, we found proliferating cochlear cell aggregates in the organ of Corti. 36687526 0 65 theme cell 65:68 arg1 transcriptomes 70:83 mouse cochlear supporting cell transcriptomes 39:83 mouse cochlear supporting cell transcriptomes 39:83 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 3 66 theme single 579:584 arg1 transcriptomes 591:604 single cell transcriptomes 579:604 single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2 579:658 Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. 36687526 5 67 theme n-linked 860:867 arg1 SIBLINGs 884:891 SIBLINGs 884:891 SIBLINGs 884:891 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 5 67 theme n-linked 860:867 arg1 glycoproteins 869:881 Called small integrin-binding ligand n-linked glycoproteins 823:881 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs) 823:892 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 2 68 theme widespread 449:458 arg1 down-regulation 460:474 widespread down-regulation 449:474 widespread down-regulation of SOX2 in neighboring cells 449:503 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 0 69 theme ERBB2 100:104 arg1 receptor 106:113 activated ERBB2 receptor 90:113 activated ERBB2 receptor 90:113 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 8 70 theme Corti 1303:1307 arg1 organ 1294:1298 the organ 1290:1298 the organ of Corti 1290:1307 Furthermore, we found proliferating cochlear cell aggregates in the organ of Corti. 36687526 4 71 with population 760:769 arg1 expression 793:802 de novo expression 785:802 de novo expression of a gene network 785:820 ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. 36687526 7 72 theme young 1152:1156 arg1 SCs 1164:1166 young adult SCs 1152:1166 young adult SCs 1152:1166 ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. 36687526 7 73 from signaling 1139:1147 arg1 SCs 1164:1166 young adult SCs 1152:1166 young adult SCs 1152:1166 ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. 36687526 1 74 theme cells 231:235 arg1 death 208:212 the death 204:212 the death of cochlear hair cells (HCs) 204:241 Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. 36687526 0 75 theme cell 7:10 arg1 analysis 27:34 Single cell RNA sequencing analysis 0:34 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor 0:113 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 0 76 theme sequencing 16:25 arg1 analysis 27:34 Single cell RNA sequencing analysis 0:34 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor 0:113 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 3 77 theme cochlear 626:633 arg1 SCs 635:637 neonatal mouse cochlear SCs 611:637 neonatal mouse cochlear SCs with activated ERBB2 611:658 Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. 36687526 1 78 theme supporting 287:296 arg1 SCs 305:307 SCs 305:307 SCs 305:307 Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. 36687526 1 78 theme supporting 287:296 arg1 cells 298:302 supporting cells 287:302 supporting cells (SCs) 287:308 Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. 36687526 5 79 link n-linked 860:867 arg1 SIBLINGs 884:891 SIBLINGs 884:891 SIBLINGs 884:891 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 5 79 link n-linked 860:867 arg1 glycoproteins 869:881 Called small integrin-binding ligand n-linked glycoproteins 823:881 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs) 823:892 Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. 36687526 2 80 theme SCs 436:438 arg1 subset 417:422 a subset 415:422 a subset of cochlear SCs 415:438 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 3 81 theme neonatal 611:618 arg1 SCs 635:637 neonatal mouse cochlear SCs 611:637 neonatal mouse cochlear SCs with activated ERBB2 611:658 Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. 36687526 4 82 theme de 785:786 arg1 expression 793:802 de novo expression 785:802 de novo expression of a gene network 785:820 ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. 36687526 2 83 theme previous 378:385 arg1 report 387:392 a previous report 376:392 a previous report 376:392 In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. 36687526 0 84 theme cochlear 45:52 arg1 transcriptomes 70:83 mouse cochlear supporting cell transcriptomes 39:83 mouse cochlear supporting cell transcriptomes 39:83 Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation. 36687526 10 85 theme novel 1503:1507 arg1 mechanism 1509:1517 a novel mechanism 1501:1517 a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea 1501:1585 Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea. 36687526 9 86 theme ERBB2 1357:1361 arg1 signaling 1363:1371 ERBB2 signaling 1357:1371 ERBB2 signaling 1357:1371 Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. 36687526 1 87 theme cochlear 217:224 arg1 HCs 238:240 HCs 238:240 HCs 238:240 Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. 36687526 1 87 theme cochlear 217:224 arg1 cells 231:235 cochlear hair cells 217:235 cochlear hair cells (HCs) 217:241 Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. 36687526 7 88 theme members 1217:1223 arg1 expression 1190:1199 protein expression 1182:1199 protein expression of gene network members 1182:1223 ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. 36687526 10 89 theme stem 1532:1535 arg1 activity 1547:1554 stem cell-like activity 1532:1554 stem cell-like activity 1532:1554 Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea. 36687526 4 90 theme cells 774:778 arg1 population 760:769 a new population 754:769 a new population of cells with de novo expression of a gene network 754:820 ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. 36366545 8 0 from differences 1349:1359 arg1 pathogenesis 1364:1375 pathogenesis 1364:1375 pathogenesis 1364:1375 Further work building on our observations may explain molecular hallmarks of HIV-2 disease progression and differences in pathogenesis between HIV-1 and HIV-2. 36366545 6 1 theme Env 1023:1025 arg1 regions 1027:1033 the analyzed Env regions 1010:1033 the analyzed Env regions 1010:1033 No differences were identified between the progressor groups in the evolution of length or charge of the analyzed Env regions. 36366545 1 2 theme molecular 137:145 arg1 properties 147:156 Env molecular properties 133:156 Env molecular properties 133:156 Limited data are available on the pathogenesis of HIV-2, and the evolution of Env molecular properties during disease progression is not fully elucidated. 36366545 5 3 located observed 877:884 arg1 progressors 896:906 slower progressors 889:906 slower progressors 889:906 Furthermore, diversity increased significantly with time in faster progressors, whereas no such change was observed in slower progressors. 36366545 5 3 located observed 877:884 arg2 change 866:871 no such change 858:871 no such change 858:871 Furthermore, diversity increased significantly with time in faster progressors, whereas no such change was observed in slower progressors. 36366545 1 4 theme properties 147:156 arg1 evolution 120:128 the evolution 116:128 the evolution of Env molecular properties during disease progression 116:183 Limited data are available on the pathogenesis of HIV-2, and the evolution of Env molecular properties during disease progression is not fully elucidated. 36366545 6 5 theme progressor 952:961 arg1 groups 963:968 the progressor groups 948:968 the progressor groups in the evolution of length or charge of the analyzed Env regions 948:1033 No differences were identified between the progressor groups in the evolution of length or charge of the analyzed Env regions. 36366545 3 6 link N-linked 503:510 arg1 sites 526:530 potential N-linked glycosylation sites 493:530 potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions 493:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 3 6 link N-linked 503:510 arg1 PNGS 533:536 PNGS 533:536 PNGS 533:536 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 3 7 theme progressor 587:596 arg1 groups 598:603 progressor groups 587:603 progressor groups 587:603 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 3 8 from number 483:488 arg1 rate 461:464 the rate 457:464 the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions 457:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 2 9 theme regions 291:297 arg1 properties 267:276 molecular properties 257:276 molecular properties of HIV-2 Env regions (V1-C3) 257:305 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 8 10 theme molecular 1296:1304 arg1 hallmarks 1306:1314 molecular hallmarks 1296:1314 molecular hallmarks of HIV-2 disease progression 1296:1343 Further work building on our observations may explain molecular hallmarks of HIV-2 disease progression and differences in pathogenesis between HIV-1 and HIV-2. 36366545 7 11 theme disease 1142:1148 arg1 course 1150:1155 the studied disease course 1130:1155 the studied disease course (median 7.9 years, interquartile range [IQR] 1130:1200 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 2 12 theme Env 287:289 arg1 V1-C3 300:304 V1-C3 300:304 V1-C3 300:304 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 2 12 theme Env 287:289 arg1 regions 291:297 HIV-2 Env regions 281:297 HIV-2 Env regions (V1-C3) 281:305 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 5 13 theme such 861:864 arg1 change 866:871 no such change 858:871 no such change 858:871 Furthermore, diversity increased significantly with time in faster progressors, whereas no such change was observed in slower progressors. 36366545 7 14 theme virus 1046:1050 arg1 use 1058:1060 Predicted virus CXCR4 use 1036:1060 Predicted virus CXCR4 use 1036:1060 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 6 15 theme regions 1027:1033 arg1 charge 1000:1005 charge 1000:1005 charge 1000:1005 No differences were identified between the progressor groups in the evolution of length or charge of the analyzed Env regions. 36366545 6 15 theme regions 1027:1033 arg1 length 990:995 length 990:995 length 990:995 No differences were identified between the progressor groups in the evolution of length or charge of the analyzed Env regions. 36366545 2 16 theme HIV-2 281:285 arg1 V1-C3 300:304 V1-C3 300:304 V1-C3 300:304 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 2 16 theme HIV-2 281:285 arg1 regions 291:297 HIV-2 Env regions 281:297 HIV-2 Env regions (V1-C3) 281:305 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 4 17 theme faster 721:726 arg1 progressors 728:738 faster progressors 721:738 faster progressors 721:738 With declining CD4+ T-cell levels, slower progressors showed, on average, a decrease in the number of PNGSs, while faster progressors showed no significant change. 36366545 4 18 theme T-cell 626:631 arg1 levels 633:638 CD4+ T-cell levels 621:638 CD4+ T-cell levels 621:638 With declining CD4+ T-cell levels, slower progressors showed, on average, a decrease in the number of PNGSs, while faster progressors showed no significant change. 36366545 7 19 theme CXCR4 1052:1056 arg1 use 1058:1060 Predicted virus CXCR4 use 1036:1060 Predicted virus CXCR4 use 1036:1060 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 3 20 from rate 461:464 arg1 number 483:488 the number 479:488 the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions 479:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 3 21 theme glycosylation 512:524 arg1 sites 526:530 potential N-linked glycosylation sites 493:530 potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions 493:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 3 21 theme glycosylation 512:524 arg1 PNGS 533:536 PNGS 533:536 PNGS 533:536 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 8 22 theme HIV-2 1319:1323 arg1 progression 1333:1343 HIV-2 disease progression 1319:1343 HIV-2 disease progression 1319:1343 Further work building on our observations may explain molecular hallmarks of HIV-2 disease progression and differences in pathogenesis between HIV-1 and HIV-2. 36366545 1 23 theme disease 165:171 arg1 progression 173:183 disease progression 165:183 disease progression 165:183 Limited data are available on the pathogenesis of HIV-2, and the evolution of Env molecular properties during disease progression is not fully elucidated. 36366545 7 24 theme viral 1106:1110 arg1 population 1112:1121 a dominating viral population 1093:1121 a dominating viral population 1093:1121 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 6 25 from groups 963:968 arg1 evolution 977:985 the evolution 973:985 the evolution of length or charge of the analyzed Env regions 973:1033 No differences were identified between the progressor groups in the evolution of length or charge of the analyzed Env regions. 36366545 2 26 from phase 348:352 arg1 participants 383:394 16 study participants 374:394 16 study participants 374:394 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 2 27 dep asymptomatic 318:329 arg1 treatment-naïve 332:346 treatment-naïve 332:346 treatment-naïve 332:346 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 6 28 theme analyzed 1014:1021 arg1 regions 1027:1033 the analyzed Env regions 1010:1033 the analyzed Env regions 1010:1033 No differences were identified between the progressor groups in the evolution of length or charge of the analyzed Env regions. 36366545 0 29 theme Intra-Patient 0:12 arg1 Evolution 14:22 Intra-Patient Evolution 0:22 Intra-Patient Evolution of HIV-2 Molecular Properties 0:52 Intra-Patient Evolution of HIV-2 Molecular Properties. 36366545 7 30 theme Predicted 1036:1044 arg1 use 1058:1060 Predicted virus CXCR4 use 1036:1060 Predicted virus CXCR4 use 1036:1060 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 2 31 from infection 361:369 arg1 participants 383:394 16 study participants 374:394 16 study participants 374:394 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 5 32 theme slower 889:894 arg1 progressors 896:906 slower progressors 889:906 slower progressors 889:906 Furthermore, diversity increased significantly with time in faster progressors, whereas no such change was observed in slower progressors. 36366545 4 33 theme PNGSs 708:712 arg1 number 698:703 the number 694:703 the number of PNGSs 694:712 With declining CD4+ T-cell levels, slower progressors showed, on average, a decrease in the number of PNGSs, while faster progressors showed no significant change. 36366545 5 34 theme faster 830:835 arg1 progressors 837:847 faster progressors 830:847 faster progressors 830:847 Furthermore, diversity increased significantly with time in faster progressors, whereas no such change was observed in slower progressors. 36366545 0 35 theme HIV-2 27:31 arg1 Properties 43:52 HIV-2 Molecular Properties 27:52 HIV-2 Molecular Properties 27:52 Intra-Patient Evolution of HIV-2 Molecular Properties. 36366545 3 36 from change 469:474 arg1 number 483:488 the number 479:488 the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions 479:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 7 37 dep course 1150:1155 arg1 years 1169:1173 median 7.9 years 1158:1173 median 7.9 years 1158:1173 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 7 37 dep course 1150:1155 arg1 range 1190:1194 interquartile range [IQR 1176:1199 interquartile range [IQR 1176:1199 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 4 38 from decrease 682:689 arg1 number 698:703 the number 694:703 the number of PNGSs 694:712 With declining CD4+ T-cell levels, slower progressors showed, on average, a decrease in the number of PNGSs, while faster progressors showed no significant change. 36366545 8 39 theme Further 1242:1248 arg1 work 1250:1253 Further work 1242:1253 Further work building on our observations 1242:1282 Further work building on our observations may explain molecular hallmarks of HIV-2 disease progression and differences in pathogenesis between HIV-1 and HIV-2. 36366545 3 40 theme V1-C3 555:559 arg1 regions 562:568 the Env (V1-C3) regions 546:568 the Env (V1-C3) regions 546:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 2 41 theme faster 413:418 arg1 progressors 430:440 faster or slower progressors 413:440 faster or slower progressors 413:440 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 7 42 theme dominating 1095:1104 arg1 population 1112:1121 a dominating viral population 1093:1121 a dominating viral population 1093:1121 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 3 43 theme N-linked 503:510 arg1 sites 526:530 potential N-linked glycosylation sites 493:530 potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions 493:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 3 43 theme N-linked 503:510 arg1 PNGS 533:536 PNGS 533:536 PNGS 533:536 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 1 44 theme HIV-2 105:109 arg1 pathogenesis 89:100 the pathogenesis 85:100 the pathogenesis of HIV-2 85:109 Limited data are available on the pathogenesis of HIV-2, and the evolution of Env molecular properties during disease progression is not fully elucidated. 36366545 4 45 theme CD4+ 621:624 arg1 levels 633:638 CD4+ T-cell levels 621:638 CD4+ T-cell levels 621:638 With declining CD4+ T-cell levels, slower progressors showed, on average, a decrease in the number of PNGSs, while faster progressors showed no significant change. 36366545 6 46 theme charge 1000:1005 arg1 evolution 977:985 the evolution 973:985 the evolution of length or charge of the analyzed Env regions 973:1033 No differences were identified between the progressor groups in the evolution of length or charge of the analyzed Env regions. 36366545 0 47 theme Properties 43:52 arg1 Evolution 14:22 Intra-Patient Evolution 0:22 Intra-Patient Evolution of HIV-2 Molecular Properties 0:52 Intra-Patient Evolution of HIV-2 Molecular Properties. 36366545 7 48 theme interquartile 1176:1188 arg1 years 1169:1173 median 7.9 years 1158:1173 median 7.9 years 1158:1173 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 7 48 theme interquartile 1176:1188 arg1 range 1190:1194 interquartile range [IQR 1176:1199 interquartile range [IQR 1176:1199 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 2 49 theme intra-patient 230:242 arg1 evolution 244:252 the intra-patient evolution 226:252 the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) 226:305 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 0 50 theme Molecular 33:41 arg1 Properties 43:52 HIV-2 Molecular Properties 27:52 HIV-2 Molecular Properties 27:52 Intra-Patient Evolution of HIV-2 Molecular Properties. 36366545 2 51 theme slower 423:428 arg1 progressors 430:440 faster or slower progressors 413:440 faster or slower progressors 413:440 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 3 52 gly glycosylation 512:524 arg2 PNGS 533:536 PNGS 533:536 PNGS 533:536 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 3 52 gly glycosylation 512:524 arg2 sites 526:530 potential N-linked glycosylation sites 493:530 potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions 493:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 6 53 theme length 990:995 arg1 evolution 977:985 the evolution 973:985 the evolution of length or charge of the analyzed Env regions 973:1033 No differences were identified between the progressor groups in the evolution of length or charge of the analyzed Env regions. 36366545 7 54 theme studied 1134:1140 arg1 course 1150:1155 the studied disease course 1130:1155 the studied disease course (median 7.9 years, interquartile range [IQR] 1130:1200 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 3 55 theme Env 550:552 arg1 regions 562:568 the Env (V1-C3) regions 546:568 the Env (V1-C3) regions 546:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 3 56 theme change 469:474 arg1 rate 461:464 the rate 457:464 the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions 457:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 7 57 from rare 1066:1069 arg1 groups 1234:1239 either progressor groups 1216:1239 either progressor groups 1216:1239 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 7 58 theme median 1158:1163 arg1 years 1169:1173 median 7.9 years 1158:1173 median 7.9 years 1158:1173 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 7 58 theme median 1158:1163 arg1 range 1190:1194 interquartile range [IQR 1176:1199 interquartile range [IQR 1176:1199 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 8 59 theme disease 1325:1331 arg1 progression 1333:1343 HIV-2 disease progression 1319:1343 HIV-2 disease progression 1319:1343 Further work building on our observations may explain molecular hallmarks of HIV-2 disease progression and differences in pathogenesis between HIV-1 and HIV-2. 36366545 2 60 from participants 383:394 arg1 phase 348:352 the asymptomatic, treatment-naïve phase 314:352 the asymptomatic, treatment-naïve phase of the infection in 16 study participants 314:394 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 7 61 theme progressor 1223:1232 arg1 groups 1234:1239 either progressor groups 1216:1239 either progressor groups 1216:1239 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 2 62 theme properties 267:276 arg1 evolution 244:252 the intra-patient evolution 226:252 the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) 226:305 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 4 63 theme significant 750:760 arg1 change 762:767 no significant change 747:767 no significant change 747:767 With declining CD4+ T-cell levels, slower progressors showed, on average, a decrease in the number of PNGSs, while faster progressors showed no significant change. 36366545 2 64 theme asymptomatic 318:329 arg1 phase 348:352 the asymptomatic, treatment-naïve phase 314:352 the asymptomatic, treatment-naïve phase of the infection in 16 study participants 314:394 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 2 65 theme molecular 257:265 arg1 properties 267:276 molecular properties 257:276 molecular properties of HIV-2 Env regions (V1-C3) 257:305 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 7 66 from groups 1234:1239 arg1 rare 1066:1069 rare 1066:1069 rare 1066:1069 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 36366545 3 67 theme potential 493:501 arg1 sites 526:530 potential N-linked glycosylation sites 493:530 potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions 493:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 3 67 theme potential 493:501 arg1 PNGS 533:536 PNGS 533:536 PNGS 533:536 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 8 68 theme progression 1333:1343 arg1 differences 1349:1359 differences 1349:1359 differences in pathogenesis between HIV-1 and HIV-2 1349:1399 Further work building on our observations may explain molecular hallmarks of HIV-2 disease progression and differences in pathogenesis between HIV-1 and HIV-2. 36366545 8 68 theme progression 1333:1343 arg1 hallmarks 1306:1314 molecular hallmarks 1296:1314 molecular hallmarks of HIV-2 disease progression 1296:1343 Further work building on our observations may explain molecular hallmarks of HIV-2 disease progression and differences in pathogenesis between HIV-1 and HIV-2. 36366545 4 69 theme slower 641:646 arg1 progressors 648:658 slower progressors 641:658 slower progressors 641:658 With declining CD4+ T-cell levels, slower progressors showed, on average, a decrease in the number of PNGSs, while faster progressors showed no significant change. 36366545 2 70 theme infection 361:369 arg1 phase 348:352 the asymptomatic, treatment-naïve phase 314:352 the asymptomatic, treatment-naïve phase of the infection in 16 study participants 314:394 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 2 71 theme study 377:381 arg1 participants 383:394 16 study participants 374:394 16 study participants 374:394 We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. 36366545 3 72 theme sites 526:530 arg1 number 483:488 the number 479:488 the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions 479:568 Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. 36366545 1 73 theme Limited 55:61 arg1 data 63:66 Limited data 55:66 Limited data 55:66 Limited data are available on the pathogenesis of HIV-2, and the evolution of Env molecular properties during disease progression is not fully elucidated. 36366545 1 74 theme Env 133:135 arg1 properties 147:156 Env molecular properties 133:156 Env molecular properties 133:156 Limited data are available on the pathogenesis of HIV-2, and the evolution of Env molecular properties during disease progression is not fully elucidated. 36366545 8 75 from hallmarks 1306:1314 arg1 pathogenesis 1364:1375 pathogenesis 1364:1375 pathogenesis 1364:1375 Further work building on our observations may explain molecular hallmarks of HIV-2 disease progression and differences in pathogenesis between HIV-1 and HIV-2. 36366545 7 76 dep rare 1066:1069 arg1 5.2-14.0 1203:1210 5.2-14.0 1203:1210 5.2-14.0 1203:1210 Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. 35509261 0 0 theme anti-FUT8 73:81 arg1 intrabody 83:91 an anti-FUT8 intrabody 70:91 an anti-FUT8 intrabody 70:91 Production of afucosylated antibodies in CHO cells by coexpression of an anti-FUT8 intrabody. 35509261 2 1 theme single 320:325 arg1 -fucosyltransferase 334:352 A single α-(1,6)-fucosyltransferase 318:352 A single α-(1,6)-fucosyltransferase (FUT8) 318:359 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 2 1 theme single 320:325 arg1 FUT8 355:358 FUT8 355:358 FUT8 355:358 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 2 1 theme single 320:325 arg1 responsible 364:374 responsible 364:374 responsible 364:374 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 6 2 theme reduced 1171:1177 arg1 fucosylation 1184:1195 reduced core fucosylation 1171:1195 reduced core fucosylation 1171:1195 IgG1-producing CHO cells expressing the intrabody secrete antibodies with reduced core fucosylation as demonstrated by lectin blot analysis and UPLC-HILIC glycan analysis. 35509261 2 3 theme residue 430:436 arg1 addition 395:402 the addition 391:402 the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans 391:488 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 1 4 theme protein 309:315 arg1 region 295:300 the Fc region 288:300 the Fc region of the protein 288:315 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 8 5 theme enhanced 1666:1673 arg1 functions 1684:1692 enhanced effector functions 1666:1692 enhanced effector functions 1666:1692 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 0 6 from Production 0:9 arg1 cells 45:49 CHO cells 41:49 CHO cells 41:49 Production of afucosylated antibodies in CHO cells by coexpression of an anti-FUT8 intrabody. 35509261 7 7 theme levels 1396:1401 arg1 production 1378:1387 the production 1374:1387 the production of g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected 1374:1508 Cells engineered to inhibit directly and specifically alpha-(1,6)-fucosyltransferase activity allows for the production of g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected. 35509261 4 8 theme biological 801:810 arg1 functions 812:820 the biological functions 797:820 the biological functions of antibodies 797:834 Several approaches have been developed to modify glycans and improve the biological functions of antibodies. 35509261 5 9 theme endoplasmic 947:957 arg1 reticulum 959:967 the endoplasmic reticulum 943:967 the endoplasmic reticulum 943:967 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 7 10 theme enhanced 1425:1432 arg1 function 1448:1455 strongly enhanced ADCC effector function 1416:1455 strongly enhanced ADCC effector function 1416:1455 Cells engineered to inhibit directly and specifically alpha-(1,6)-fucosyltransferase activity allows for the production of g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected. 35509261 8 11 theme practical 1575:1583 arg1 applicability 1585:1597 broad practical applicability 1569:1597 broad practical applicability 1569:1597 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 0 12 theme intrabody 83:91 arg1 coexpression 54:65 coexpression 54:65 coexpression of an anti-FUT8 intrabody 54:91 Production of afucosylated antibodies in CHO cells by coexpression of an anti-FUT8 intrabody. 35509261 5 13 theme antibody 1087:1094 arg1 N-glycan 1072:1079 the Fc N-glycan 1065:1079 the Fc N-glycan of an antibody 1065:1094 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 4 14 theme Several 728:734 arg1 approaches 736:745 Several approaches 728:745 Several approaches 728:745 Several approaches have been developed to modify glycans and improve the biological functions of antibodies. 35509261 1 15 attach linked 260:265 arg2 N-glycans 250:258 the N-glycans 246:258 the N-glycans linked to asparagine 297 of the Fc region of the protein 246:315 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 1 15 attach linked 260:265 arg1 297 281:283 asparagine 297 270:283 asparagine 297 of the Fc region of the protein 270:315 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 7 16 theme ADCC 1434:1437 arg1 function 1448:1455 strongly enhanced ADCC effector function 1416:1455 strongly enhanced ADCC effector function 1416:1455 Cells engineered to inhibit directly and specifically alpha-(1,6)-fucosyltransferase activity allows for the production of g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected. 35509261 7 17 with IgGs 1406:1409 arg1 function 1448:1455 strongly enhanced ADCC effector function 1416:1455 strongly enhanced ADCC effector function 1416:1455 Cells engineered to inhibit directly and specifically alpha-(1,6)-fucosyltransferase activity allows for the production of g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected. 35509261 7 18 theme fucosylation 1481:1492 arg1 level 1472:1476 the level 1468:1476 the level of fucosylation 1468:1492 Cells engineered to inhibit directly and specifically alpha-(1,6)-fucosyltransferase activity allows for the production of g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected. 35509261 2 19 link N-linked 473:480 arg1 glycans 482:488 the N-linked glycans 469:488 the N-linked glycans 469:488 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 6 20 theme blot 1223:1226 arg1 analysis 1228:1235 lectin blot analysis 1216:1235 lectin blot analysis 1216:1235 IgG1-producing CHO cells expressing the intrabody secrete antibodies with reduced core fucosylation as demonstrated by lectin blot analysis and UPLC-HILIC glycan analysis. 35509261 2 21 theme GlcNAc 451:456 arg1 residue 458:464 the first GlcNAc residue 441:464 the first GlcNAc residue of the N-linked glycans 441:488 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 2 21 theme GlcNAc 451:456 arg1 glycans 482:488 the N-linked glycans 469:488 the N-linked glycans 469:488 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 2 22 theme fucose 423:428 arg1 residue 430:436 an α-1,6-linked fucose residue 407:436 an α-1,6-linked fucose residue 407:436 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 5 23 theme Golgi 973:977 arg1 apparatus 979:987 Golgi apparatus 973:987 Golgi apparatus 973:987 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 3 24 dep safety 687:692 arg1 concerns 694:701 concerns 694:701 concerns 694:701 Antibodies missing this core fucose show a significantly enhanced ADCC and increased antitumor activity, which could help reduce therapeutic dose requirement, potentially translating into reduced safety concerns and manufacturing costs. 35509261 3 25 theme reduced 679:685 arg1 safety 687:692 reduced safety concerns 679:701 reduced safety concerns 679:701 Antibodies missing this core fucose show a significantly enhanced ADCC and increased antitumor activity, which could help reduce therapeutic dose requirement, potentially translating into reduced safety concerns and manufacturing costs. 35509261 3 26 theme core 515:518 arg1 fucose 520:525 this core fucose 510:525 this core fucose 510:525 Antibodies missing this core fucose show a significantly enhanced ADCC and increased antitumor activity, which could help reduce therapeutic dose requirement, potentially translating into reduced safety concerns and manufacturing costs. 35509261 7 27 theme -fucosyltransferase 1334:1352 arg1 activity 1354:1361 alpha-(1,6)-fucosyltransferase activity 1323:1361 alpha-(1,6)-fucosyltransferase activity 1323:1361 Cells engineered to inhibit directly and specifically alpha-(1,6)-fucosyltransferase activity allows for the production of g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected. 35509261 8 28 theme efficient 1525:1533 arg1 method 1535:1540 The quick and efficient method 1511:1540 The quick and efficient method described here 1511:1555 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 8 29 theme broad 1569:1573 arg1 applicability 1585:1597 broad practical applicability 1569:1597 broad practical applicability 1569:1597 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 4 30 theme antibodies 825:834 arg1 functions 812:820 the biological functions 797:820 the biological functions of antibodies 797:834 Several approaches have been developed to modify glycans and improve the biological functions of antibodies. 35509261 7 31 theme effector 1439:1446 arg1 function 1448:1455 strongly enhanced ADCC effector function 1416:1455 strongly enhanced ADCC effector function 1416:1455 Cells engineered to inhibit directly and specifically alpha-(1,6)-fucosyltransferase activity allows for the production of g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected. 35509261 7 32 theme g/L 1392:1394 arg1 levels 1396:1401 g/L levels 1392:1401 g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected 1392:1508 Cells engineered to inhibit directly and specifically alpha-(1,6)-fucosyltransferase activity allows for the production of g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected. 35509261 2 33 theme 1,6 330:332 arg1 -fucosyltransferase 334:352 A single α-(1,6)-fucosyltransferase 318:352 A single α-(1,6)-fucosyltransferase (FUT8) 318:359 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 2 33 theme 1,6 330:332 arg1 FUT8 355:358 FUT8 355:358 FUT8 355:358 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 2 33 theme 1,6 330:332 arg1 responsible 364:374 responsible 364:374 responsible 364:374 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 0 34 theme antibodies 27:36 arg1 Production 0:9 Production 0:9 Production of afucosylated antibodies in CHO cells by coexpression of an anti-FUT8 intrabody 0:91 Production of afucosylated antibodies in CHO cells by coexpression of an anti-FUT8 intrabody. 35509261 2 35 link α-1,6-linked 410:421 arg1 residue 430:436 an α-1,6-linked fucose residue 407:436 an α-1,6-linked fucose residue 407:436 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 7 36 theme IgGs 1406:1409 arg1 levels 1396:1401 g/L levels 1392:1401 g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected 1392:1508 Cells engineered to inhibit directly and specifically alpha-(1,6)-fucosyltransferase activity allows for the production of g/L levels of IgGs with strongly enhanced ADCC effector function, for which the level of fucosylation can be selected. 35509261 1 37 theme antibody-dependent 173:190 arg1 ADCC 220:223 ADCC 220:223 ADCC 220:223 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 1 37 theme antibody-dependent 173:190 arg1 cytotoxicity 206:217 antibody-dependent cell-mediated cytotoxicity 173:217 antibody-dependent cell-mediated cytotoxicity (ADCC) 173:224 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 0 38 theme afucosylated 14:25 arg1 antibodies 27:36 afucosylated antibodies 14:36 afucosylated antibodies 14:36 Production of afucosylated antibodies in CHO cells by coexpression of an anti-FUT8 intrabody. 35509261 1 39 theme asparagine 270:279 arg1 297 281:283 asparagine 297 270:283 asparagine 297 of the Fc region of the protein 270:315 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 5 40 theme Fc 1069:1070 arg1 N-glycan 1072:1079 the Fc N-glycan 1065:1079 the Fc N-glycan of an antibody 1065:1094 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 1 41 theme effector 99:106 arg1 functions 108:116 Some effector functions 94:116 Some effector functions 94:116 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 1 41 theme effector 99:106 arg1 cytotoxicity 206:217 antibody-dependent cell-mediated cytotoxicity 173:217 antibody-dependent cell-mediated cytotoxicity (ADCC) 173:224 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 8 42 with antibodies 1650:1659 arg1 functions 1684:1692 enhanced effector functions 1666:1692 enhanced effector functions 1666:1692 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 1 43 theme cell-mediated 192:204 arg1 ADCC 220:223 ADCC 220:223 ADCC 220:223 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 1 43 theme cell-mediated 192:204 arg1 cytotoxicity 206:217 antibody-dependent cell-mediated cytotoxicity 173:217 antibody-dependent cell-mediated cytotoxicity (ADCC) 173:224 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 0 44 theme CHO 41:43 arg1 cells 45:49 CHO cells 41:49 CHO cells 41:49 Production of afucosylated antibodies in CHO cells by coexpression of an anti-FUT8 intrabody. 35509261 3 45 theme manufacturing 707:719 arg1 costs 721:725 manufacturing costs 707:725 manufacturing costs 707:725 Antibodies missing this core fucose show a significantly enhanced ADCC and increased antitumor activity, which could help reduce therapeutic dose requirement, potentially translating into reduced safety concerns and manufacturing costs. 35509261 2 46 theme glycans 482:488 arg1 residue 458:464 the first GlcNAc residue 441:464 the first GlcNAc residue of the N-linked glycans 441:488 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 2 46 theme glycans 482:488 arg1 glycans 482:488 the N-linked glycans 469:488 the N-linked glycans 469:488 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 5 47 theme N-glycan 1072:1079 arg1 activity 1017:1024 FUT8 activity 1012:1024 FUT8 activity 1012:1024 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 5 47 theme N-glycan 1072:1079 arg1 core-fucosylation 1044:1060 the core-fucosylation 1040:1060 the core-fucosylation of the Fc N-glycan of an antibody 1040:1094 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 5 48 theme FUT8 1012:1015 arg1 activity 1017:1024 FUT8 activity 1012:1024 FUT8 activity 1012:1024 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 2 49 theme α-1,6-linked 410:421 arg1 residue 430:436 an α-1,6-linked fucose residue 407:436 an α-1,6-linked fucose residue 407:436 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 6 50 with antibodies 1155:1164 arg1 fucosylation 1184:1195 reduced core fucosylation 1171:1195 reduced core fucosylation 1171:1195 IgG1-producing CHO cells expressing the intrabody secrete antibodies with reduced core fucosylation as demonstrated by lectin blot analysis and UPLC-HILIC glycan analysis. 35509261 2 51 theme N-linked 473:480 arg1 glycans 482:488 the N-linked glycans 469:488 the N-linked glycans 469:488 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 3 52 theme enhanced 548:555 arg1 ADCC 557:560 a significantly enhanced ADCC 532:560 a significantly enhanced ADCC 532:560 Antibodies missing this core fucose show a significantly enhanced ADCC and increased antitumor activity, which could help reduce therapeutic dose requirement, potentially translating into reduced safety concerns and manufacturing costs. 35509261 8 53 theme effector 1675:1682 arg1 functions 1684:1692 enhanced effector functions 1666:1692 enhanced effector functions 1666:1692 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 0 54 gly afucosylated 14:25 arg1 antibodies 27:36 afucosylated antibodies 14:36 afucosylated antibodies 14:36 Production of afucosylated antibodies in CHO cells by coexpression of an anti-FUT8 intrabody. 35509261 6 55 theme CHO 1112:1114 arg1 cells 1116:1120 IgG1-producing CHO cells 1097:1120 IgG1-producing CHO cells expressing the intrabody 1097:1145 IgG1-producing CHO cells expressing the intrabody secrete antibodies with reduced core fucosylation as demonstrated by lectin blot analysis and UPLC-HILIC glycan analysis. 35509261 5 56 theme membrane-associated 879:897 arg1 intrabody 909:917 a membrane-associated anti-FUT8 intrabody 877:917 a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus 877:987 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 6 57 gly fucosylation 1184:1195 arg1 antibodies 1155:1164 antibodies 1155:1164 antibodies with reduced core fucosylation 1155:1195 IgG1-producing CHO cells expressing the intrabody secrete antibodies with reduced core fucosylation as demonstrated by lectin blot analysis and UPLC-HILIC glycan analysis. 35509261 1 58 theme Fc 292:293 arg1 region 295:300 the Fc region 288:300 the Fc region of the protein 288:315 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 3 59 theme therapeutic 620:630 arg1 requirement 637:647 therapeutic dose requirement 620:647 therapeutic dose requirement 620:647 Antibodies missing this core fucose show a significantly enhanced ADCC and increased antitumor activity, which could help reduce therapeutic dose requirement, potentially translating into reduced safety concerns and manufacturing costs. 35509261 5 60 theme anti-FUT8 899:907 arg1 intrabody 909:917 a membrane-associated anti-FUT8 intrabody 877:917 a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus 877:987 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 1 61 theme region 295:300 arg1 297 281:283 asparagine 297 270:283 asparagine 297 of the Fc region of the protein 270:315 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 3 62 theme dose 632:635 arg1 requirement 637:647 therapeutic dose requirement 620:647 therapeutic dose requirement 620:647 Antibodies missing this core fucose show a significantly enhanced ADCC and increased antitumor activity, which could help reduce therapeutic dose requirement, potentially translating into reduced safety concerns and manufacturing costs. 35509261 3 63 theme increased 566:574 arg1 activity 586:593 increased antitumor activity 566:593 increased antitumor activity 566:593 Antibodies missing this core fucose show a significantly enhanced ADCC and increased antitumor activity, which could help reduce therapeutic dose requirement, potentially translating into reduced safety concerns and manufacturing costs. 35509261 6 64 theme glycan 1252:1257 arg1 analysis 1259:1266 UPLC-HILIC glycan analysis 1241:1266 UPLC-HILIC glycan analysis 1241:1266 IgG1-producing CHO cells expressing the intrabody secrete antibodies with reduced core fucosylation as demonstrated by lectin blot analysis and UPLC-HILIC glycan analysis. 35509261 5 65 theme intrabody 909:917 arg1 expression 863:872 expression 863:872 expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus 863:987 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 8 66 theme therapeutic 1638:1648 arg1 antibodies 1650:1659 next-generation therapeutic antibodies 1622:1659 next-generation therapeutic antibodies with enhanced effector functions 1622:1692 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 6 67 theme core 1179:1182 arg1 fucosylation 1184:1195 reduced core fucosylation 1171:1195 reduced core fucosylation 1171:1195 IgG1-producing CHO cells expressing the intrabody secrete antibodies with reduced core fucosylation as demonstrated by lectin blot analysis and UPLC-HILIC glycan analysis. 35509261 6 68 theme UPLC-HILIC 1241:1250 arg1 analysis 1259:1266 UPLC-HILIC glycan analysis 1241:1266 UPLC-HILIC glycan analysis 1241:1266 IgG1-producing CHO cells expressing the intrabody secrete antibodies with reduced core fucosylation as demonstrated by lectin blot analysis and UPLC-HILIC glycan analysis. 35509261 3 69 theme antitumor 576:584 arg1 activity 586:593 increased antitumor activity 566:593 increased antitumor activity 566:593 Antibodies missing this core fucose show a significantly enhanced ADCC and increased antitumor activity, which could help reduce therapeutic dose requirement, potentially translating into reduced safety concerns and manufacturing costs. 35509261 1 70 theme immunoglobulin 130:143 arg1 IgG 148:150 IgG 148:150 IgG 148:150 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 1 70 theme immunoglobulin 130:143 arg1 G 145:145 immunoglobulin G 130:145 immunoglobulin G (IgG) antibodies 130:162 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 8 71 theme next-generation 1622:1636 arg1 antibodies 1650:1659 next-generation therapeutic antibodies 1622:1659 next-generation therapeutic antibodies with enhanced effector functions 1622:1692 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 2 72 theme first 445:449 arg1 residue 458:464 the first GlcNAc residue 441:464 the first GlcNAc residue of the N-linked glycans 441:488 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 2 72 theme first 445:449 arg1 glycans 482:488 the N-linked glycans 469:488 the N-linked glycans 469:488 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 6 73 theme IgG1-producing 1097:1110 arg1 cells 1116:1120 IgG1-producing CHO cells 1097:1120 IgG1-producing CHO cells expressing the intrabody 1097:1145 IgG1-producing CHO cells expressing the intrabody secrete antibodies with reduced core fucosylation as demonstrated by lectin blot analysis and UPLC-HILIC glycan analysis. 35509261 6 74 theme lectin 1216:1221 arg1 analysis 1228:1235 lectin blot analysis 1216:1235 lectin blot analysis 1216:1235 IgG1-producing CHO cells expressing the intrabody secrete antibodies with reduced core fucosylation as demonstrated by lectin blot analysis and UPLC-HILIC glycan analysis. 35509261 1 75 theme G 145:145 arg1 antibodies 153:162 immunoglobulin G (IgG) antibodies 130:162 immunoglobulin G (IgG) antibodies 130:162 Some effector functions prompted by immunoglobulin G (IgG) antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC), strongly depend on the N-glycans linked to asparagine 297 of the Fc region of the protein. 35509261 8 76 theme quick 1515:1519 arg1 method 1535:1540 The quick and efficient method 1511:1540 The quick and efficient method described here 1511:1555 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 8 77 contain have 1564:1567 arg2 applicability 1585:1597 broad practical applicability 1569:1597 broad practical applicability 1569:1597 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 8 77 contain have 1564:1567 arg1 method 1535:1540 The quick and efficient method 1511:1540 The quick and efficient method described here 1511:1555 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35509261 2 78 theme α- 327:328 arg1 -fucosyltransferase 334:352 A single α-(1,6)-fucosyltransferase 318:352 A single α-(1,6)-fucosyltransferase (FUT8) 318:359 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 2 78 theme α- 327:328 arg1 FUT8 355:358 FUT8 355:358 FUT8 355:358 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 2 78 theme α- 327:328 arg1 responsible 364:374 responsible 364:374 responsible 364:374 A single α-(1,6)-fucosyltransferase (FUT8) is responsible for catalyzing the addition of an α-1,6-linked fucose residue to the first GlcNAc residue of the N-linked glycans. 35509261 5 79 gly core-fucosylation 1044:1060 arg1 N-glycan 1072:1079 the Fc N-glycan 1065:1079 the Fc N-glycan of an antibody 1065:1094 Here, we demonstrate that expression of a membrane-associated anti-FUT8 intrabody engineered to reside in the endoplasmic reticulum and Golgi apparatus can efficiently reduce FUT8 activity and therefore the core-fucosylation of the Fc N-glycan of an antibody. 35509261 8 80 theme antibodies 1650:1659 arg1 development 1607:1617 the development 1603:1617 the development of next-generation therapeutic antibodies with enhanced effector functions 1603:1692 The quick and efficient method described here should have broad practical applicability for the development of next-generation therapeutic antibodies with enhanced effector functions. 35348113 5 0 theme high 851:854 arg1 affinity 856:863 high affinity 851:863 high affinity 851:863 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 6 1 theme key 929:931 arg1 molecule 933:940 a key molecule 927:940 a key molecule in tumor progression 927:961 Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression. 35348113 5 2 theme GPC1-dependent 687:700 arg1 secretion 707:715 GPC1-dependent FGF2 secretion 687:715 GPC1-dependent FGF2 secretion 687:715 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 5 3 theme FGF2 702:705 arg1 secretion 707:715 GPC1-dependent FGF2 secretion 687:715 GPC1-dependent FGF2 secretion 687:715 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 5 4 theme sulfate 803:809 arg1 chains 811:816 the heparan sulfate chains 791:816 the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity 791:863 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 1 5 theme Fibroblast 74:83 arg1 factor 133:138 a tumor cell survival factor 111:138 a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism 111:228 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 1 5 theme Fibroblast 74:83 arg1 factor 92:97 Fibroblast growth factor 2 74:99 Fibroblast growth factor 2 (FGF2) 74:106 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 1 5 theme Fibroblast 74:83 arg1 FGF2 102:105 FGF2 102:105 FGF2 102:105 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 5 6 theme GPC1 821:824 arg1 chains 811:816 the heparan sulfate chains 791:816 the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity 791:863 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 5 7 theme N-linked 749:756 arg1 groups 766:771 N-linked sulfate groups 749:771 N-linked sulfate groups 749:771 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 1 8 theme growth 85:90 arg1 factor 133:138 a tumor cell survival factor 111:138 a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism 111:228 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 1 8 theme growth 85:90 arg1 factor 92:97 Fibroblast growth factor 2 74:99 Fibroblast growth factor 2 (FGF2) 74:106 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 1 8 theme growth 85:90 arg1 FGF2 102:105 FGF2 102:105 FGF2 102:105 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 3 9 theme diverse 365:371 arg1 subclasses 373:382 the diverse subclasses 361:382 the diverse subclasses consisting of syndecans, perlecans, glypicans, and others 361:440 Unexpectedly, we found that among the diverse subclasses consisting of syndecans, perlecans, glypicans, and others, Glypican-1 (GPC1) is the principle and rate-limiting factor that drives unconventional secretion of FGF2. 35348113 6 10 from molecule 933:940 arg1 progression 951:961 tumor progression 945:961 tumor progression 945:961 Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression. 35348113 3 11 theme FGF2 543:546 arg1 secretion 530:538 unconventional secretion 515:538 unconventional secretion of FGF2 515:546 Unexpectedly, we found that among the diverse subclasses consisting of syndecans, perlecans, glypicans, and others, Glypican-1 (GPC1) is the principle and rate-limiting factor that drives unconventional secretion of FGF2. 35348113 6 12 contain have 879:882 arg1 findings 870:877 Our findings 866:877 Our findings 866:877 Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression. 35348113 6 12 contain have 879:882 arg2 implications 890:901 broad implications 884:901 broad implications for the role of GPC1 as a key molecule in tumor progression 884:961 Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression. 35348113 6 13 theme GPC1 919:922 arg1 role 911:914 the role 907:914 the role of GPC1 as a key molecule in tumor progression 907:961 Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression. 35348113 3 14 theme unconventional 515:528 arg1 secretion 530:538 unconventional secretion 515:538 unconventional secretion of FGF2 515:546 Unexpectedly, we found that among the diverse subclasses consisting of syndecans, perlecans, glypicans, and others, Glypican-1 (GPC1) is the principle and rate-limiting factor that drives unconventional secretion of FGF2. 35348113 1 15 theme extracellular 169:181 arg1 space 183:187 the extracellular space 165:187 the extracellular space 165:187 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 2 16 theme essential 295:303 arg1 role 305:308 an essential role 292:308 an essential role 292:308 Cell surface heparan sulfate proteoglycans are known to play an essential role in this process. 35348113 3 17 theme rate-limiting 482:494 arg1 Glypican-1 443:452 Glypican-1 443:452 Glypican-1 (GPC1) 443:459 Unexpectedly, we found that among the diverse subclasses consisting of syndecans, perlecans, glypicans, and others, Glypican-1 (GPC1) is the principle and rate-limiting factor that drives unconventional secretion of FGF2. 35348113 3 17 theme rate-limiting 482:494 arg1 factor 496:501 the principle and rate-limiting factor 464:501 factor 496:501 Unexpectedly, we found that among the diverse subclasses consisting of syndecans, perlecans, glypicans, and others, Glypican-1 (GPC1) is the principle and rate-limiting factor that drives unconventional secretion of FGF2. 35348113 3 18 theme principle 468:476 arg1 Glypican-1 443:452 Glypican-1 443:452 Glypican-1 (GPC1) 443:459 Unexpectedly, we found that among the diverse subclasses consisting of syndecans, perlecans, glypicans, and others, Glypican-1 (GPC1) is the principle and rate-limiting factor that drives unconventional secretion of FGF2. 35348113 3 18 theme principle 468:476 arg1 factor 496:501 the principle and rate-limiting factor 464:501 factor 496:501 Unexpectedly, we found that among the diverse subclasses consisting of syndecans, perlecans, glypicans, and others, Glypican-1 (GPC1) is the principle and rate-limiting factor that drives unconventional secretion of FGF2. 35348113 0 19 theme fibroblast 46:55 arg1 factor 64:69 fibroblast growth factor 2 46:71 fibroblast growth factor 2 46:71 Glypican-1 drives unconventional secretion of fibroblast growth factor 2. 35348113 5 20 theme structural 666:675 arg1 basis 677:681 the structural basis 662:681 the structural basis for GPC1-dependent FGF2 secretion 662:715 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 4 21 theme FGF2 604:607 arg1 signaling 609:617 FGF2 signaling 604:617 FGF2 signaling into cells 604:628 By contrast, we demonstrate GPC1 to be dispensable for FGF2 signaling into cells. 35348113 0 22 theme unconventional 18:31 arg1 secretion 33:41 unconventional secretion 18:41 unconventional secretion of fibroblast growth factor 2 18:71 Glypican-1 drives unconventional secretion of fibroblast growth factor 2. 35348113 5 23 theme sulfate 758:764 arg1 groups 766:771 N-linked sulfate groups 749:771 N-linked sulfate groups 749:771 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 0 24 theme factor 64:69 arg1 secretion 33:41 unconventional secretion 18:41 unconventional secretion of fibroblast growth factor 2 18:71 Glypican-1 drives unconventional secretion of fibroblast growth factor 2. 35348113 5 25 link N-linked 749:756 arg1 groups 766:771 N-linked sulfate groups 749:771 N-linked sulfate groups 749:771 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 0 26 theme growth 57:62 arg1 factor 64:69 fibroblast growth factor 2 46:71 fibroblast growth factor 2 46:71 Glypican-1 drives unconventional secretion of fibroblast growth factor 2. 35348113 6 27 theme broad 884:888 arg1 implications 890:901 broad implications 884:901 broad implications for the role of GPC1 as a key molecule in tumor progression 884:961 Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression. 35348113 5 28 theme first 642:646 arg1 insights 648:655 first insights 642:655 first insights into the structural basis for GPC1-dependent FGF2 secretion 642:715 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 5 29 with disaccharides 730:742 arg1 groups 766:771 N-linked sulfate groups 749:771 N-linked sulfate groups 749:771 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 2 30 theme sulfate 252:258 arg1 proteoglycans 260:272 Cell surface heparan sulfate proteoglycans 231:272 Cell surface heparan sulfate proteoglycans 231:272 Cell surface heparan sulfate proteoglycans are known to play an essential role in this process. 35348113 1 31 theme unconventional 195:208 arg1 mechanism 220:228 an unconventional secretory mechanism 192:228 an unconventional secretory mechanism 192:228 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 2 32 theme heparan 244:250 arg1 proteoglycans 260:272 Cell surface heparan sulfate proteoglycans 231:272 Cell surface heparan sulfate proteoglycans 231:272 Cell surface heparan sulfate proteoglycans are known to play an essential role in this process. 35348113 1 33 theme tumor 113:117 arg1 factor 133:138 a tumor cell survival factor 111:138 a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism 111:228 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 1 33 theme tumor 113:117 arg1 factor 92:97 Fibroblast growth factor 2 74:99 Fibroblast growth factor 2 (FGF2) 74:106 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 1 34 theme secretory 210:218 arg1 mechanism 220:228 an unconventional secretory mechanism 192:228 an unconventional secretory mechanism 192:228 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 2 35 theme surface 236:242 arg1 proteoglycans 260:272 Cell surface heparan sulfate proteoglycans 231:272 Cell surface heparan sulfate proteoglycans 231:272 Cell surface heparan sulfate proteoglycans are known to play an essential role in this process. 35348113 5 36 theme heparan 795:801 arg1 chains 811:816 the heparan sulfate chains 791:816 the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity 791:863 We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. 35348113 1 37 theme cell 119:122 arg1 factor 133:138 a tumor cell survival factor 111:138 a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism 111:228 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 1 37 theme cell 119:122 arg1 factor 92:97 Fibroblast growth factor 2 74:99 Fibroblast growth factor 2 (FGF2) 74:106 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 2 38 theme Cell 231:234 arg1 proteoglycans 260:272 Cell surface heparan sulfate proteoglycans 231:272 Cell surface heparan sulfate proteoglycans 231:272 Cell surface heparan sulfate proteoglycans are known to play an essential role in this process. 35348113 1 39 theme survival 124:131 arg1 factor 133:138 a tumor cell survival factor 111:138 a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism 111:228 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 1 39 theme survival 124:131 arg1 factor 92:97 Fibroblast growth factor 2 74:99 Fibroblast growth factor 2 (FGF2) 74:106 Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. 35348113 6 40 theme tumor 945:949 arg1 progression 951:961 tumor progression 945:961 tumor progression 945:961 Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression. 35091294 1 0 theme protein 165:171 arg1 drug 173:176 protein drug's 165:178 a protein drug's stability 163:188 Acidic N-linked glycan content is often associated with a protein drug's stability, efficacy and immune response. 35091294 10 1 from features 1596:1603 arg1 profile 1620:1626 an N-glycan profile 1608:1626 an N-glycan profile 1608:1626 Using analytical scale chromatography, features in an N-glycan profile were easily interrogated to well below a 0.1% relative abundance. 35091294 9 2 theme mass 1538:1541 arg1 spectrometry 1543:1554 mass spectrometry 1538:1554 mass spectrometry 1538:1554 The separation technique itself can be accomplished with a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry. 35091294 0 3 theme mode 86:89 arg1 chromatography 91:104 mixed mode chromatography 80:104 mixed mode chromatography 80:104 High sensitivity acidic N-glycan profiling with MS-enhancing derivatization and mixed mode chromatography. 35091294 7 4 theme glycans 1089:1095 arg1 separation 1075:1084 a class separation 1067:1084 a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection 1067:1170 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 8 5 theme glycan 1187:1192 arg1 species 1194:1200 These labeled glycan species 1173:1200 These labeled glycan species 1173:1200 These labeled glycan species are separated according to their charge and with an added level of resolution imparted by the reversed phase retention mechanism. 35091294 11 6 theme species 1849:1855 arg1 number 1810:1815 a number 1808:1815 a number of unique phosphorylated glycan species 1808:1855 As such, it became possible to characterize N-glycans from recombinant beta glucuronidase and to quickly identify a number of unique phosphorylated glycan species. 35091294 10 7 theme 0.1 1669:1671 arg1 % 1672:1672 % 1672:1672 % 1672:1672 Using analytical scale chromatography, features in an N-glycan profile were easily interrogated to well below a 0.1% relative abundance. 35091294 7 8 theme class 1069:1073 arg1 separation 1075:1084 a class separation 1067:1084 a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection 1067:1170 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 2 9 theme glycans 277:283 arg1 those 296:300 those 296:300 those 296:300 It has often been a challenge to analyze these types of glycans, including those that are differentiated by the incorporation of N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues. 35091294 2 9 theme glycans 277:283 arg1 types 268:272 these types 262:272 these types 262:272 It has often been a challenge to analyze these types of glycans, including those that are differentiated by the incorporation of N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues. 35091294 4 10 theme Hybrid 562:567 arg1 surfaces 592:599 Hybrid silica chromatographic surfaces 562:599 Hybrid silica chromatographic surfaces 562:599 Hybrid silica chromatographic surfaces are used to improve recoveries during a column's initial use and to eliminate the need for column conditioning. 35091294 7 11 theme MS 1159:1160 arg1 detection 1162:1170 positive ion mode MS detection 1141:1170 positive ion mode MS detection 1141:1170 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 9 12 theme high 1470:1473 arg1 sensitivity 1475:1485 high sensitivity 1470:1485 high sensitivity detection 1470:1495 The separation technique itself can be accomplished with a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry. 35091294 8 13 theme reversed 1296:1303 arg1 mechanism 1321:1329 the reversed phase retention mechanism 1292:1329 the reversed phase retention mechanism 1292:1329 These labeled glycan species are separated according to their charge and with an added level of resolution imparted by the reversed phase retention mechanism. 35091294 9 14 theme ionic 1395:1399 arg1 strength 1401:1408 low ionic strength 1391:1408 a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry 1389:1554 The separation technique itself can be accomplished with a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry. 35091294 7 15 theme mode 1154:1157 arg1 detection 1162:1170 positive ion mode MS detection 1141:1170 positive ion mode MS detection 1141:1170 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 5 16 theme citrate 862:868 arg1 eluent 881:886 a citrate containing eluent 860:886 a citrate containing eluent 860:886 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 2 17 theme N-glycolyl 370:379 arg1 residues 404:411 N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues 350:411 N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues 350:411 It has often been a challenge to analyze these types of glycans, including those that are differentiated by the incorporation of N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues. 35091294 5 18 theme glycans 753:759 arg1 loss 730:733 the loss 726:733 the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification 726:826 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 8 19 theme retention 1311:1319 arg1 mechanism 1321:1329 the reversed phase retention mechanism 1292:1329 the reversed phase retention mechanism 1292:1329 These labeled glycan species are separated according to their charge and with an added level of resolution imparted by the reversed phase retention mechanism. 35091294 8 20 theme added 1254:1258 arg1 level 1260:1264 an added level 1251:1264 an added level of resolution imparted by the reversed phase retention mechanism 1251:1329 These labeled glycan species are separated according to their charge and with an added level of resolution imparted by the reversed phase retention mechanism. 35091294 2 21 dep N-acetyl 350:357 arg1 NANA 360:363 NANA 360:363 NANA 360:363 It has often been a challenge to analyze these types of glycans, including those that are differentiated by the incorporation of N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues. 35091294 7 22 theme positive 1141:1148 arg1 detection 1162:1170 positive ion mode MS detection 1141:1170 positive ion mode MS detection 1141:1170 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 10 23 theme % 1672:1672 arg1 abundance 1683:1691 a 0.1% relative abundance 1667:1691 well below a 0.1% relative abundance 1656:1691 Using analytical scale chromatography, features in an N-glycan profile were easily interrogated to well below a 0.1% relative abundance. 35091294 10 24 theme scale 1574:1578 arg1 chromatography 1580:1593 analytical scale chromatography 1563:1593 analytical scale chromatography 1563:1593 Using analytical scale chromatography, features in an N-glycan profile were easily interrogated to well below a 0.1% relative abundance. 35091294 0 25 theme mixed 80:84 arg1 chromatography 91:104 mixed mode chromatography 80:104 mixed mode chromatography 80:104 High sensitivity acidic N-glycan profiling with MS-enhancing derivatization and mixed mode chromatography. 35091294 10 26 theme analytical 1563:1572 arg1 chromatography 1580:1593 analytical scale chromatography 1563:1593 analytical scale chromatography 1563:1593 Using analytical scale chromatography, features in an N-glycan profile were easily interrogated to well below a 0.1% relative abundance. 35091294 11 27 theme unique 1820:1825 arg1 species 1849:1855 unique phosphorylated glycan species 1820:1855 unique phosphorylated glycan species 1820:1855 As such, it became possible to characterize N-glycans from recombinant beta glucuronidase and to quickly identify a number of unique phosphorylated glycan species. 35091294 0 28 theme High 0:3 arg1 sensitivity 5:15 High sensitivity 0:15 High sensitivity 0:15 High sensitivity acidic N-glycan profiling with MS-enhancing derivatization and mixed mode chromatography. 35091294 6 29 theme glycan 938:943 arg1 species 945:951 both singly and doubly phosphorylated glycan species 900:951 both singly and doubly phosphorylated glycan species 900:951 Yields for both singly and doubly phosphorylated glycan species are markedly improved. 35091294 1 30 theme Acidic 107:112 arg1 content 130:136 Acidic N-linked glycan content 107:136 Acidic N-linked glycan content 107:136 Acidic N-linked glycan content is often associated with a protein drug's stability, efficacy and immune response. 35091294 10 31 theme N-glycan 1611:1618 arg1 profile 1620:1626 an N-glycan profile 1608:1626 an N-glycan profile 1608:1626 Using analytical scale chromatography, features in an N-glycan profile were easily interrogated to well below a 0.1% relative abundance. 35091294 0 32 theme N-glycan 24:31 arg1 profiling 33:41 N-glycan profiling 24:41 N-glycan profiling 24:41 High sensitivity acidic N-glycan profiling with MS-enhancing derivatization and mixed mode chromatography. 35091294 4 33 theme column 692:697 arg1 conditioning 699:710 column conditioning 692:710 column conditioning 692:710 Hybrid silica chromatographic surfaces are used to improve recoveries during a column's initial use and to eliminate the need for column conditioning. 35091294 9 34 theme strength 1401:1408 arg1 gradient 1410:1417 a low ionic strength gradient 1389:1417 a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry 1389:1554 The separation technique itself can be accomplished with a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry. 35091294 1 35 theme N-linked 114:121 arg1 content 130:136 Acidic N-linked glycan content 107:136 Acidic N-linked glycan content 107:136 Acidic N-linked glycan content is often associated with a protein drug's stability, efficacy and immune response. 35091294 3 36 theme established 529:539 arg1 methodologies 547:559 established HILIC methodologies 529:559 established HILIC methodologies 529:559 In this study, a strategy for rapid N-glycan profiling by mixed mode chromatography is proposed as a complement to established HILIC methodologies. 35091294 11 37 theme recombinant 1753:1763 arg1 glucuronidase 1770:1782 recombinant beta glucuronidase 1753:1782 recombinant beta glucuronidase 1753:1782 As such, it became possible to characterize N-glycans from recombinant beta glucuronidase and to quickly identify a number of unique phosphorylated glycan species. 35091294 1 38 theme glycan 123:128 arg1 content 130:136 Acidic N-linked glycan content 107:136 Acidic N-linked glycan content 107:136 Acidic N-linked glycan content is often associated with a protein drug's stability, efficacy and immune response. 35091294 1 39 theme immune 204:209 arg1 response 211:218 immune response 204:218 immune response 204:218 Acidic N-linked glycan content is often associated with a protein drug's stability, efficacy and immune response. 35091294 1 39 theme immune 204:209 arg1 stability 180:188 a protein drug's stability 163:188 a protein drug's stability 163:188 Acidic N-linked glycan content is often associated with a protein drug's stability, efficacy and immune response. 35091294 8 40 theme labeled 1179:1185 arg1 species 1194:1200 These labeled glycan species 1173:1200 These labeled glycan species 1173:1200 These labeled glycan species are separated according to their charge and with an added level of resolution imparted by the reversed phase retention mechanism. 35091294 5 41 theme containing 870:879 arg1 eluent 881:886 a citrate containing eluent 860:886 a citrate containing eluent 860:886 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 7 42 theme reversed 1018:1025 arg1 separation 1033:1042 a mixed mode anion exchange reversed phase separation 990:1042 a mixed mode anion exchange reversed phase separation 990:1042 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 7 43 theme ion 1150:1152 arg1 detection 1162:1170 positive ion mode MS detection 1141:1170 positive ion mode MS detection 1141:1170 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 2 44 theme acid 392:395 arg1 residues 404:411 N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues 350:411 N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues 350:411 It has often been a challenge to analyze these types of glycans, including those that are differentiated by the incorporation of N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues. 35091294 5 45 theme labeled 738:744 arg1 species 795:801 phosphorylated glycan species 773:801 especially phosphorylated glycan species 762:801 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 5 45 theme labeled 738:744 arg1 glycans 753:759 labeled acidic glycans 738:759 labeled acidic glycans 738:759 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 11 46 theme glycan 1842:1847 arg1 species 1849:1855 unique phosphorylated glycan species 1820:1855 unique phosphorylated glycan species 1820:1855 As such, it became possible to characterize N-glycans from recombinant beta glucuronidase and to quickly identify a number of unique phosphorylated glycan species. 35091294 7 47 theme phase 1027:1031 arg1 separation 1033:1042 a mixed mode anion exchange reversed phase separation 990:1042 a mixed mode anion exchange reversed phase separation 990:1042 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 8 48 theme resolution 1269:1278 arg1 level 1260:1264 an added level 1251:1264 an added level of resolution imparted by the reversed phase retention mechanism 1251:1329 These labeled glycan species are separated according to their charge and with an added level of resolution imparted by the reversed phase retention mechanism. 35091294 2 49 theme residues 404:411 arg1 incorporation 333:345 the incorporation 329:345 the incorporation of N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues 329:411 It has often been a challenge to analyze these types of glycans, including those that are differentiated by the incorporation of N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues. 35091294 10 50 dep well 1656:1659 arg1 below 1661:1665 below 1661:1665 below 1661:1665 Using analytical scale chromatography, features in an N-glycan profile were easily interrogated to well below a 0.1% relative abundance. 35091294 2 51 theme neuraminic 381:390 arg1 acid 392:395 neuraminic acid 381:395 N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues 350:411 It has often been a challenge to analyze these types of glycans, including those that are differentiated by the incorporation of N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues. 35091294 2 51 theme neuraminic 381:390 arg1 NGNA 398:401 NGNA 398:401 NGNA 398:401 It has often been a challenge to analyze these types of glycans, including those that are differentiated by the incorporation of N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues. 35091294 5 52 theme acidic 746:751 arg1 species 795:801 phosphorylated glycan species 773:801 especially phosphorylated glycan species 762:801 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 5 52 theme acidic 746:751 arg1 glycans 753:759 labeled acidic glycans 738:759 labeled acidic glycans 738:759 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 7 53 theme anion 1003:1007 arg1 exchange 1009:1016 a mixed mode anion exchange 990:1016 a mixed mode anion exchange reversed phase separation 990:1042 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 6 54 theme phosphorylated 923:936 arg1 species 945:951 both singly and doubly phosphorylated glycan species 900:951 both singly and doubly phosphorylated glycan species 900:951 Yields for both singly and doubly phosphorylated glycan species are markedly improved. 35091294 3 55 theme HILIC 541:545 arg1 methodologies 547:559 established HILIC methodologies 529:559 established HILIC methodologies 529:559 In this study, a strategy for rapid N-glycan profiling by mixed mode chromatography is proposed as a complement to established HILIC methodologies. 35091294 0 56 with acidic 17:22 arg1 chromatography 91:104 mixed mode chromatography 80:104 mixed mode chromatography 80:104 High sensitivity acidic N-glycan profiling with MS-enhancing derivatization and mixed mode chromatography. 35091294 0 56 with acidic 17:22 arg1 derivatization 61:74 MS-enhancing derivatization 48:74 MS-enhancing derivatization 48:74 High sensitivity acidic N-glycan profiling with MS-enhancing derivatization and mixed mode chromatography. 35091294 3 57 theme rapid 444:448 arg1 profiling 459:467 rapid N-glycan profiling 444:467 rapid N-glycan profiling by mixed mode chromatography 444:496 In this study, a strategy for rapid N-glycan profiling by mixed mode chromatography is proposed as a complement to established HILIC methodologies. 35091294 0 58 theme MS-enhancing 48:59 arg1 derivatization 61:74 MS-enhancing derivatization 48:74 MS-enhancing derivatization 48:74 High sensitivity acidic N-glycan profiling with MS-enhancing derivatization and mixed mode chromatography. 35091294 9 59 theme separation 1336:1345 arg1 technique 1347:1355 The separation technique 1332:1355 The separation technique itself 1332:1362 The separation technique itself can be accomplished with a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry. 35091294 7 60 theme exchange 1009:1016 arg1 separation 1033:1042 a mixed mode anion exchange reversed phase separation 990:1042 a mixed mode anion exchange reversed phase separation 990:1042 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 5 61 theme phosphorylated 773:786 arg1 species 795:801 phosphorylated glycan species 773:801 especially phosphorylated glycan species 762:801 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 5 61 theme phosphorylated 773:786 arg1 glycans 753:759 labeled acidic glycans 738:759 labeled acidic glycans 738:759 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 11 62 from glucuronidase 1770:1782 arg1 N-glycans 1738:1746 N-glycans 1738:1746 N-glycans from recombinant beta glucuronidase 1738:1782 As such, it became possible to characterize N-glycans from recombinant beta glucuronidase and to quickly identify a number of unique phosphorylated glycan species. 35091294 3 63 theme N-glycan 450:457 arg1 profiling 459:467 rapid N-glycan profiling 444:467 rapid N-glycan profiling by mixed mode chromatography 444:496 In this study, a strategy for rapid N-glycan profiling by mixed mode chromatography is proposed as a complement to established HILIC methodologies. 35091294 11 64 theme phosphorylated 1827:1840 arg1 species 1849:1855 unique phosphorylated glycan species 1820:1855 unique phosphorylated glycan species 1820:1855 As such, it became possible to characterize N-glycans from recombinant beta glucuronidase and to quickly identify a number of unique phosphorylated glycan species. 35091294 7 65 theme mixed 992:996 arg1 exchange 1009:1016 a mixed mode anion exchange 990:1016 a mixed mode anion exchange reversed phase separation 990:1042 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 11 66 theme beta 1765:1768 arg1 glucuronidase 1770:1782 recombinant beta glucuronidase 1753:1782 recombinant beta glucuronidase 1753:1782 As such, it became possible to characterize N-glycans from recombinant beta glucuronidase and to quickly identify a number of unique phosphorylated glycan species. 35091294 9 67 dep 22 mM 1437:1441 arg1 to 1434:1435 to 1434:1435 to 1434:1435 The separation technique itself can be accomplished with a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry. 35091294 4 68 theme initial 650:656 arg1 use 658:660 a column's initial use 639:660 a column's initial use 639:660 Hybrid silica chromatographic surfaces are used to improve recoveries during a column's initial use and to eliminate the need for column conditioning. 35091294 5 69 theme eluent 881:886 arg1 use 853:855 the use 849:855 the use of a citrate containing eluent 849:886 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 4 70 theme chromatographic 576:590 arg1 surfaces 592:599 Hybrid silica chromatographic surfaces 562:599 Hybrid silica chromatographic surfaces 562:599 Hybrid silica chromatographic surfaces are used to improve recoveries during a column's initial use and to eliminate the need for column conditioning. 35091294 7 71 theme mode 998:1001 arg1 exchange 1009:1016 a mixed mode anion exchange 990:1016 a mixed mode anion exchange reversed phase separation 990:1042 Combined with a mixed mode anion exchange reversed phase separation, these advances afford a class separation of glycans derivatized with labels designed to enhance positive ion mode MS detection. 35091294 8 72 theme phase 1305:1309 arg1 mechanism 1321:1329 the reversed phase retention mechanism 1292:1329 the reversed phase retention mechanism 1292:1329 These labeled glycan species are separated according to their charge and with an added level of resolution imparted by the reversed phase retention mechanism. 35091294 2 73 theme N-acetyl 350:357 arg1 residues 404:411 N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues 350:411 N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues 350:411 It has often been a challenge to analyze these types of glycans, including those that are differentiated by the incorporation of N-acetyl (NANA) and N-glycolyl neuraminic acid (NGNA) residues. 35091294 4 74 theme silica 569:574 arg1 surfaces 592:599 Hybrid silica chromatographic surfaces 562:599 Hybrid silica chromatographic surfaces 562:599 Hybrid silica chromatographic surfaces are used to improve recoveries during a column's initial use and to eliminate the need for column conditioning. 35091294 1 75 link N-linked 114:121 arg1 content 130:136 Acidic N-linked glycan content 107:136 Acidic N-linked glycan content 107:136 Acidic N-linked glycan content is often associated with a protein drug's stability, efficacy and immune response. 35091294 5 76 theme SPE 811:813 arg1 purification 815:826 SPE purification 811:826 SPE purification 811:826 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 9 77 theme sensitivity 1475:1485 arg1 detection 1487:1495 high sensitivity detection 1470:1495 high sensitivity detection 1470:1495 The separation technique itself can be accomplished with a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry. 35091294 3 78 theme mixed 472:476 arg1 chromatography 483:496 mixed mode chromatography 472:496 mixed mode chromatography 472:496 In this study, a strategy for rapid N-glycan profiling by mixed mode chromatography is proposed as a complement to established HILIC methodologies. 35091294 9 79 theme ammonium 1443:1450 arg1 formate 1452:1458 0 to 22 mM ammonium formate 1432:1458 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry 1432:1554 The separation technique itself can be accomplished with a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry. 35091294 9 80 theme low 1391:1393 arg1 strength 1401:1408 low ionic strength 1391:1408 a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry 1389:1554 The separation technique itself can be accomplished with a low ionic strength gradient running from 0 to 22 mM ammonium formate such that high sensitivity detection can be achieved by both fluorescence and mass spectrometry. 35091294 5 81 theme glycan 788:793 arg1 species 795:801 phosphorylated glycan species 773:801 especially phosphorylated glycan species 762:801 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 5 81 theme glycan 788:793 arg1 glycans 753:759 labeled acidic glycans 738:759 labeled acidic glycans 738:759 In addition, the loss of labeled acidic glycans, especially phosphorylated glycan species, during SPE purification is addressed through the use of a citrate containing eluent. 35091294 4 82 used used 605:608 arg2 surfaces 592:599 Hybrid silica chromatographic surfaces 562:599 Hybrid silica chromatographic surfaces 562:599 Hybrid silica chromatographic surfaces are used to improve recoveries during a column's initial use and to eliminate the need for column conditioning. 35091294 3 83 theme mode 478:481 arg1 chromatography 483:496 mixed mode chromatography 472:496 mixed mode chromatography 472:496 In this study, a strategy for rapid N-glycan profiling by mixed mode chromatography is proposed as a complement to established HILIC methodologies. 35091294 10 84 theme relative 1674:1681 arg1 abundance 1683:1691 a 0.1% relative abundance 1667:1691 well below a 0.1% relative abundance 1656:1691 Using analytical scale chromatography, features in an N-glycan profile were easily interrogated to well below a 0.1% relative abundance. 37108663 3 0 theme sporangial 609:618 arg1 release 620:626 sporangial release 609:626 sporangial release 609:626 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 1 1 theme Asparagine 170:179 arg1 glycosylation 197:209 Asparagine (Asn, N)-linked glycosylation 170:209 Asparagine (Asn, N)-linked glycosylation 170:209 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 1 1 theme Asparagine 170:179 arg1 process 226:232 a conserved process 214:232 a conserved process 214:232 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 1 2 theme essential 241:249 arg1 modification 270:281 an essential post-translational modification 238:281 an essential post-translational modification 238:281 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 7 3 theme PcSTT3B 1211:1217 arg1 gene 1219:1222 the PcSTT3B gene 1207:1222 the PcSTT3B gene 1207:1222 By using a CRISPR/Cas9-mediated gene replacement system to delete the PcSTT3B gene, the transformants impaired mycelial growth, sporangial release, zoospore production, and virulence. 37108663 1 4 theme endoplasmic 345:355 arg1 ER 368:369 ER 368:369 ER 368:369 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 1 4 theme endoplasmic 345:355 arg1 reticulum 357:365 endoplasmic reticulum 345:365 endoplasmic reticulum (ER) 345:370 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 3 5 theme Phytophthora 656:667 arg1 capsici 669:675 Phytophthora capsici 656:675 Phytophthora capsici 656:675 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 8 6 theme display 1410:1416 arg1 content 1435:1441 display low glycoprotein content 1410:1441 display low glycoprotein content in the mycelia 1410:1456 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 8 7 dep stress 1388:1393 arg1 TM 1403:1404 inducer TM 1395:1404 inducer TM 1395:1404 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 1 8 theme post-translational 251:268 arg1 modification 270:281 an essential post-translational modification 238:281 an essential post-translational modification 238:281 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 6 9 theme catalytic 1080:1088 arg1 activity 1090:1097 catalytic activity 1080:1097 catalytic activity 1080:1097 The PcSTT3B gene has catalytic activity and is highly conservative in P. capsici. 37108663 8 10 theme ER 1503:1504 arg1 responses 1513:1521 ER stress responses 1503:1521 ER stress responses 1503:1521 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 1 11 from motif 308:312 arg1 ER 368:369 ER 368:369 ER 368:369 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 1 11 from motif 308:312 arg1 reticulum 357:365 endoplasmic reticulum 345:365 endoplasmic reticulum (ER) 345:370 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 3 12 theme N-glycosylation 536:550 arg1 TM 575:576 TM 575:576 TM 575:576 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 3 12 theme N-glycosylation 536:550 arg1 tunicamycin 562:572 an N-glycosylation inhibitor tunicamycin 533:572 an N-glycosylation inhibitor tunicamycin (TM) 533:577 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 8 13 gly glycoprotein 1422:1433 arg1 glycoprotein 1422:1433 display low glycoprotein content 1410:1441 display low glycoprotein content in the mycelia 1410:1456 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 5 14 theme complex 940:946 arg1 subunit 893:899 a core subunit 886:899 a core subunit of the oligosaccharyltransferase (OST) complex 886:946 As a core subunit of the oligosaccharyltransferase (OST) complex, the staurosporine and temperature sensive 3B (STT3B) subunit were critical for the catalytic activity of OST. 37108663 3 15 theme growth 735:740 arg1 development 742:752 oomycete growth development 726:752 oomycete growth development 726:752 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 4 16 theme catalytic 769:777 arg1 enzymes 779:785 the key catalytic enzymes 761:785 the key catalytic enzymes involved in N-glycosylation 761:813 Among the key catalytic enzymes involved in N-glycosylation, the PcSTT3B gene was characterized by its functions in P. capsici. 37108663 3 17 theme inhibitor 552:560 arg1 TM 575:576 TM 575:576 TM 575:576 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 3 17 theme inhibitor 552:560 arg1 tunicamycin 562:572 an N-glycosylation inhibitor tunicamycin 533:572 an N-glycosylation inhibitor tunicamycin (TM) 533:577 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 7 18 theme replacement 1178:1188 arg1 system 1190:1195 a CRISPR/Cas9-mediated gene replacement system 1150:1195 a CRISPR/Cas9-mediated gene replacement system 1150:1195 By using a CRISPR/Cas9-mediated gene replacement system to delete the PcSTT3B gene, the transformants impaired mycelial growth, sporangial release, zoospore production, and virulence. 37108663 7 19 theme sporangial 1269:1278 arg1 release 1280:1286 sporangial release 1269:1286 sporangial release 1269:1286 By using a CRISPR/Cas9-mediated gene replacement system to delete the PcSTT3B gene, the transformants impaired mycelial growth, sporangial release, zoospore production, and virulence. 37108663 0 20 gly N-glycosylation 83:97 arg1 Pathogenicity 131:143 Pathogenicity 131:143 Pathogenicity 131:143 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 0 20 gly N-glycosylation 83:97 arg1 Development 115:125 Development 115:125 Development 115:125 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 2 21 theme N-glycosylation 390:404 arg1 functions 421:429 biological functions 410:429 biological functions of key catalytic enzymes involved in this process 410:479 The mechanism of N-glycosylation and biological functions of key catalytic enzymes involved in this process are rarely documented for oomycetes. 37108663 2 21 theme N-glycosylation 390:404 arg1 mechanism 377:385 The mechanism 373:385 The mechanism of N-glycosylation 373:404 The mechanism of N-glycosylation and biological functions of key catalytic enzymes involved in this process are rarely documented for oomycetes. 37108663 4 22 from functions 858:866 arg1 capsici 874:880 capsici 874:880 capsici 874:880 Among the key catalytic enzymes involved in N-glycosylation, the PcSTT3B gene was characterized by its functions in P. capsici. 37108663 5 23 theme 3B 991:992 arg1 subunit 1002:1008 temperature sensive 3B (STT3B) subunit 971:1008 temperature sensive 3B (STT3B) subunit 971:1008 As a core subunit of the oligosaccharyltransferase (OST) complex, the staurosporine and temperature sensive 3B (STT3B) subunit were critical for the catalytic activity of OST. 37108663 6 24 theme PcSTT3B 1063:1069 arg1 conservative 1113:1124 conservative 1113:1124 conservative 1113:1124 The PcSTT3B gene has catalytic activity and is highly conservative in P. capsici. 37108663 6 24 theme PcSTT3B 1063:1069 arg1 gene 1071:1074 The PcSTT3B gene 1059:1074 The PcSTT3B gene 1059:1074 The PcSTT3B gene has catalytic activity and is highly conservative in P. capsici. 37108663 7 25 theme CRISPR/Cas9-mediated 1152:1171 arg1 system 1190:1195 a CRISPR/Cas9-mediated gene replacement system 1150:1195 a CRISPR/Cas9-mediated gene replacement system 1150:1195 By using a CRISPR/Cas9-mediated gene replacement system to delete the PcSTT3B gene, the transformants impaired mycelial growth, sporangial release, zoospore production, and virulence. 37108663 3 26 theme oomycete 726:733 arg1 development 742:752 oomycete growth development 726:752 oomycete growth development 726:752 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 1 27 dep Asparagine 170:179 arg1 N 187:187 N 187:187 N 187:187 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 1 27 dep Asparagine 170:179 arg1 Asn 182:184 Asn 182:184 Asn 182:184 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 8 28 from stress 1388:1393 arg1 mycelia 1450:1456 the mycelia 1446:1456 the mycelia 1446:1456 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 2 29 theme enzymes 448:454 arg1 functions 421:429 biological functions 410:429 biological functions of key catalytic enzymes involved in this process 410:479 The mechanism of N-glycosylation and biological functions of key catalytic enzymes involved in this process are rarely documented for oomycetes. 37108663 2 29 theme enzymes 448:454 arg1 mechanism 377:385 The mechanism 373:385 The mechanism of N-glycosylation 373:404 The mechanism of N-glycosylation and biological functions of key catalytic enzymes involved in this process are rarely documented for oomycetes. 37108663 5 30 theme OST 1054:1056 arg1 activity 1042:1049 the catalytic activity 1028:1049 the catalytic activity of OST 1028:1056 As a core subunit of the oligosaccharyltransferase (OST) complex, the staurosporine and temperature sensive 3B (STT3B) subunit were critical for the catalytic activity of OST. 37108663 6 31 contain has 1076:1078 arg2 activity 1090:1097 catalytic activity 1080:1097 catalytic activity 1080:1097 The PcSTT3B gene has catalytic activity and is highly conservative in P. capsici. 37108663 6 31 contain has 1076:1078 arg1 conservative 1113:1124 conservative 1113:1124 conservative 1113:1124 The PcSTT3B gene has catalytic activity and is highly conservative in P. capsici. 37108663 6 31 contain has 1076:1078 arg1 gene 1071:1074 The PcSTT3B gene 1059:1074 The PcSTT3B gene 1059:1074 The PcSTT3B gene has catalytic activity and is highly conservative in P. capsici. 37108663 6 32 from capsici 1132:1138 arg1 conservative 1113:1124 conservative 1113:1124 conservative 1113:1124 The PcSTT3B gene has catalytic activity and is highly conservative in P. capsici. 37108663 6 32 from capsici 1132:1138 arg1 gene 1071:1074 The PcSTT3B gene 1059:1074 The PcSTT3B gene 1059:1074 The PcSTT3B gene has catalytic activity and is highly conservative in P. capsici. 37108663 2 33 theme catalytic 438:446 arg1 enzymes 448:454 key catalytic enzymes 434:454 key catalytic enzymes involved in this process 434:479 The mechanism of N-glycosylation and biological functions of key catalytic enzymes involved in this process are rarely documented for oomycetes. 37108663 9 34 theme P. 1634:1635 arg1 capsici 1637:1643 P. capsici 1634:1643 P. capsici 1634:1643 Therefore, PcSTT3B was involved in the development, pathogenicity, and N-glycosylation of P. capsici. 37108663 4 35 theme key 765:767 arg1 enzymes 779:785 the key catalytic enzymes 761:785 the key catalytic enzymes involved in N-glycosylation 761:813 Among the key catalytic enzymes involved in N-glycosylation, the PcSTT3B gene was characterized by its functions in P. capsici. 37108663 8 36 theme inducer 1395:1401 arg1 TM 1403:1404 inducer TM 1395:1404 inducer TM 1395:1404 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 1 37 theme -linked 189:195 arg1 glycosylation 197:209 Asparagine (Asn, N)-linked glycosylation 170:209 Asparagine (Asn, N)-linked glycosylation 170:209 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 1 37 theme -linked 189:195 arg1 process 226:232 a conserved process 214:232 a conserved process 214:232 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 0 38 theme PcSTT3B 20:26 arg1 Characterization 0:15 Characterization 0:15 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 0:168 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 5 39 theme sensive 983:989 arg1 subunit 1002:1008 temperature sensive 3B (STT3B) subunit 971:1008 temperature sensive 3B (STT3B) subunit 971:1008 As a core subunit of the oligosaccharyltransferase (OST) complex, the staurosporine and temperature sensive 3B (STT3B) subunit were critical for the catalytic activity of OST. 37108663 6 40 theme P. 1129:1130 arg1 capsici 1132:1138 P. capsici 1129:1138 P. capsici 1129:1138 The PcSTT3B gene has catalytic activity and is highly conservative in P. capsici. 37108663 8 41 from content 1435:1441 arg1 mycelia 1450:1456 the mycelia 1446:1456 the mycelia 1446:1456 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 0 42 theme Key 33:35 arg1 Subunit 63:69 a Key Oligosaccharyltransferase Subunit 31:69 a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici 31:167 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 1 43 theme NXT/S 302:306 arg1 motif 308:312 the NXT/S motif 298:312 the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER) 298:370 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 0 44 theme Phytophthora 148:159 arg1 capsici 161:167 Phytophthora capsici 148:167 Phytophthora capsici 148:167 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 0 45 from N-glycosylation 83:97 arg1 Pathogenicity 131:143 Pathogenicity 131:143 Pathogenicity 131:143 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 0 45 from N-glycosylation 83:97 arg1 Development 115:125 Development 115:125 Development 115:125 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 3 46 theme mycelial 592:599 arg1 growth 601:606 mycelial growth 592:606 mycelial growth 592:606 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 2 47 theme biological 410:419 arg1 functions 421:429 biological functions 410:429 biological functions of key catalytic enzymes involved in this process 410:479 The mechanism of N-glycosylation and biological functions of key catalytic enzymes involved in this process are rarely documented for oomycetes. 37108663 1 48 from reticulum 357:365 arg1 motif 308:312 the NXT/S motif 298:312 the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER) 298:370 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 9 49 gly N-glycosylation 1615:1629 arg1 capsici 1637:1643 P. capsici 1634:1643 P. capsici 1634:1643 Therefore, PcSTT3B was involved in the development, pathogenicity, and N-glycosylation of P. capsici. 37108663 7 50 theme zoospore 1289:1296 arg1 production 1298:1307 zoospore production 1289:1307 zoospore production 1289:1307 By using a CRISPR/Cas9-mediated gene replacement system to delete the PcSTT3B gene, the transformants impaired mycelial growth, sporangial release, zoospore production, and virulence. 37108663 1 51 from polypeptides 329:340 arg1 ER 368:369 ER 368:369 ER 368:369 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 1 51 from polypeptides 329:340 arg1 reticulum 357:365 endoplasmic reticulum 345:365 endoplasmic reticulum (ER) 345:370 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 3 52 theme zoospore 633:640 arg1 production 642:651 zoospore production 633:651 zoospore production 633:651 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 5 53 theme temperature 971:981 arg1 subunit 1002:1008 temperature sensive 3B (STT3B) subunit 971:1008 temperature sensive 3B (STT3B) subunit 971:1008 As a core subunit of the oligosaccharyltransferase (OST) complex, the staurosporine and temperature sensive 3B (STT3B) subunit were critical for the catalytic activity of OST. 37108663 5 54 theme oligosaccharyltransferase 908:932 arg1 complex 940:946 the oligosaccharyltransferase (OST) complex 904:946 the oligosaccharyltransferase (OST) complex 904:946 As a core subunit of the oligosaccharyltransferase (OST) complex, the staurosporine and temperature sensive 3B (STT3B) subunit were critical for the catalytic activity of OST. 37108663 0 55 theme Oligosaccharyltransferase 37:61 arg1 Subunit 63:69 a Key Oligosaccharyltransferase Subunit 31:69 a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici 31:167 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 0 56 theme capsici 161:167 arg1 Pathogenicity 131:143 Pathogenicity 131:143 Pathogenicity 131:143 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 0 56 theme capsici 161:167 arg1 Development 115:125 Development 115:125 Development 115:125 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 5 57 theme catalytic 1032:1040 arg1 activity 1042:1049 the catalytic activity 1028:1049 the catalytic activity of OST 1028:1056 As a core subunit of the oligosaccharyltransferase (OST) complex, the staurosporine and temperature sensive 3B (STT3B) subunit were critical for the catalytic activity of OST. 37108663 8 58 theme glycoprotein 1422:1433 arg1 content 1435:1441 display low glycoprotein content 1410:1441 display low glycoprotein content in the mycelia 1410:1456 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 1 59 link -linked 189:195 arg1 glycosylation 197:209 Asparagine (Asn, N)-linked glycosylation 170:209 Asparagine (Asn, N)-linked glycosylation 170:209 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 1 59 link -linked 189:195 arg1 process 226:232 a conserved process 214:232 a conserved process 214:232 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 1 60 theme nascent 321:327 arg1 polypeptides 329:340 the nascent polypeptides 317:340 the nascent polypeptides in endoplasmic reticulum (ER) 317:370 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 8 61 theme low 1418:1420 arg1 content 1435:1441 display low glycoprotein content 1410:1441 display low glycoprotein content in the mycelia 1410:1456 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 6 62 from conservative 1113:1124 arg1 capsici 1132:1138 P. capsici 1129:1138 P. capsici 1129:1138 The PcSTT3B gene has catalytic activity and is highly conservative in P. capsici. 37108663 8 63 theme ER 1385:1386 arg1 stress 1388:1393 an ER stress inducer TM and display low glycoprotein content in the mycelia 1382:1456 stress 1388:1393 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 1 64 theme conserved 216:224 arg1 glycosylation 197:209 Asparagine (Asn, N)-linked glycosylation 170:209 Asparagine (Asn, N)-linked glycosylation 170:209 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 1 64 theme conserved 216:224 arg1 process 226:232 a conserved process 214:232 a conserved process 214:232 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 0 65 from Role 107:110 arg1 Pathogenicity 131:143 Pathogenicity 131:143 Pathogenicity 131:143 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 0 65 from Role 107:110 arg1 Development 115:125 Development 115:125 Development 115:125 Characterization of PcSTT3B as a Key Oligosaccharyltransferase Subunit Involved in N-glycosylation and Its Role in Development and Pathogenicity of Phytophthora capsici. 37108663 5 66 theme STT3B 995:999 arg1 subunit 1002:1008 temperature sensive 3B (STT3B) subunit 971:1008 temperature sensive 3B (STT3B) subunit 971:1008 As a core subunit of the oligosaccharyltransferase (OST) complex, the staurosporine and temperature sensive 3B (STT3B) subunit were critical for the catalytic activity of OST. 37108663 9 67 theme capsici 1637:1643 arg1 pathogenicity 1596:1608 pathogenicity 1596:1608 pathogenicity 1596:1608 Therefore, PcSTT3B was involved in the development, pathogenicity, and N-glycosylation of P. capsici. 37108663 9 67 theme capsici 1637:1643 arg1 N-glycosylation 1615:1629 N-glycosylation 1615:1629 N-glycosylation 1615:1629 Therefore, PcSTT3B was involved in the development, pathogenicity, and N-glycosylation of P. capsici. 37108663 9 67 theme capsici 1637:1643 arg1 development 1583:1593 development 1583:1593 development 1583:1593 Therefore, PcSTT3B was involved in the development, pathogenicity, and N-glycosylation of P. capsici. 37108663 8 68 theme PcSTT3B-deleted 1329:1343 arg1 transformants 1345:1357 The PcSTT3B-deleted transformants 1325:1357 The PcSTT3B-deleted transformants 1325:1357 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 8 68 theme PcSTT3B-deleted 1329:1343 arg1 sensitive 1369:1377 sensitive 1369:1377 sensitive 1369:1377 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 8 69 theme stress 1506:1511 arg1 responses 1513:1521 ER stress responses 1503:1521 ER stress responses 1503:1521 The PcSTT3B-deleted transformants were more sensitive to an ER stress inducer TM and display low glycoprotein content in the mycelia, suggesting that PcSTT3B was associated with ER stress responses and N-glycosylation. 37108663 3 70 theme capsici 669:675 arg1 production 642:651 zoospore production 633:651 zoospore production 633:651 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 3 70 theme capsici 669:675 arg1 growth 601:606 mycelial growth 592:606 mycelial growth 592:606 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 3 70 theme capsici 669:675 arg1 release 620:626 sporangial release 609:626 sporangial release 609:626 In this study, an N-glycosylation inhibitor tunicamycin (TM) hampered the mycelial growth, sporangial release, and zoospore production of Phytophthora capsici, indicating that N-glycosylation was crucial for oomycete growth development. 37108663 4 71 theme PcSTT3B 820:826 arg1 gene 828:831 the PcSTT3B gene 816:831 the PcSTT3B gene 816:831 Among the key catalytic enzymes involved in N-glycosylation, the PcSTT3B gene was characterized by its functions in P. capsici. 37108663 5 72 theme core 888:891 arg1 subunit 893:899 a core subunit 886:899 a core subunit of the oligosaccharyltransferase (OST) complex 886:946 As a core subunit of the oligosaccharyltransferase (OST) complex, the staurosporine and temperature sensive 3B (STT3B) subunit were critical for the catalytic activity of OST. 37108663 9 73 dep development 1583:1593 arg1 the 1579:1581 the 1579:1581 the 1579:1581 Therefore, PcSTT3B was involved in the development, pathogenicity, and N-glycosylation of P. capsici. 37108663 1 74 theme polypeptides 329:340 arg1 motif 308:312 the NXT/S motif 298:312 the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER) 298:370 Asparagine (Asn, N)-linked glycosylation is a conserved process and an essential post-translational modification that occurs on the NXT/S motif of the nascent polypeptides in endoplasmic reticulum (ER). 37108663 2 75 theme key 434:436 arg1 enzymes 448:454 key catalytic enzymes 434:454 key catalytic enzymes involved in this process 434:479 The mechanism of N-glycosylation and biological functions of key catalytic enzymes involved in this process are rarely documented for oomycetes. 37108663 7 76 theme mycelial 1252:1259 arg1 growth 1261:1266 mycelial growth 1252:1266 mycelial growth 1252:1266 By using a CRISPR/Cas9-mediated gene replacement system to delete the PcSTT3B gene, the transformants impaired mycelial growth, sporangial release, zoospore production, and virulence. 37108663 7 77 theme gene 1173:1176 arg1 system 1190:1195 a CRISPR/Cas9-mediated gene replacement system 1150:1195 a CRISPR/Cas9-mediated gene replacement system 1150:1195 By using a CRISPR/Cas9-mediated gene replacement system to delete the PcSTT3B gene, the transformants impaired mycelial growth, sporangial release, zoospore production, and virulence. 35336854 0 0 theme Tembusu 69:75 arg1 Virus 77:81 Tembusu Virus 69:81 Tembusu Virus in Ducks 69:90 A Single Mutation at Position 120 in the Envelope Protein Attenuates Tembusu Virus in Ducks. 35336854 0 1 from Mutation 9:16 arg1 Protein 50:56 the Envelope Protein 37:56 the Envelope Protein 37:56 A Single Mutation at Position 120 in the Envelope Protein Attenuates Tembusu Virus in Ducks. 35336854 6 2 from loss 915:918 arg1 ducks 931:935 ducks 931:935 ducks 931:935 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 4 3 theme molecular 425:433 arg1 basis 435:439 the key molecular basis 417:439 the key molecular basis of attenuation 417:454 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35336854 6 4 theme amino 800:804 arg1 mutation 811:818 a D120N amino acid mutation 792:818 a D120N amino acid mutation located in domain II of the E protein 792:856 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 4 theme amino 800:804 arg1 responsible 862:872 responsible 862:872 responsible 862:872 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 4 5 theme wild-type 515:523 arg1 strain 542:547 the wild-type TMUV-FX2010 (FX) strain 511:547 the wild-type TMUV-FX2010 (FX) strain 511:547 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35336854 5 6 theme E 686:686 arg1 responsible 701:711 responsible 701:711 responsible 701:711 The results show that the envelope (E) protein was responsible for attenuation and loss of transmission in ducks. 35336854 5 6 theme E 686:686 arg1 protein 689:695 the envelope (E) protein 672:695 the envelope (E) protein 672:695 The results show that the envelope (E) protein was responsible for attenuation and loss of transmission in ducks. 35336854 4 7 theme chimeric 457:464 arg1 viruses 482:488 chimeric and site mutant viruses 457:488 chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain 457:547 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35336854 7 8 theme extra 976:980 arg1 glycosylation 1009:1021 an extra high-mannose type N-linked glycosylation 973:1021 an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P 973:1052 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 7 8 theme extra 976:980 arg1 NLG 1024:1026 NLG 1024:1026 NLG 1024:1026 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 7 9 theme tissue 1113:1118 arg1 tropism 1120:1126 tissue tropism 1113:1126 tissue tropism 1113:1126 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 7 10 theme wild-type 1072:1080 arg1 TMUV 1082:1085 the wild-type TMUV 1068:1085 the wild-type TMUV 1068:1085 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 6 11 theme acid 806:809 arg1 mutation 811:818 a D120N amino acid mutation 792:818 a D120N amino acid mutation located in domain II of the E protein 792:856 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 11 theme acid 806:809 arg1 responsible 862:872 responsible 862:872 responsible 862:872 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 12 from 180P 923:926 arg1 ducks 931:935 ducks 931:935 ducks 931:935 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 7 13 from tropism 1120:1126 arg1 ducks 1160:1164 ducks 1160:1164 ducks 1160:1164 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 8 14 theme E 1207:1207 arg1 protein 1209:1215 the E protein 1203:1215 the E protein 1203:1215 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 8 15 theme molecular 1226:1234 arg1 N120 1195:1198 N120 1195:1198 N120 in the E protein 1195:1215 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 8 15 theme molecular 1226:1234 arg1 basis 1236:1240 a key molecular basis 1220:1240 a key molecular basis of TMUV attenuation in ducks 1220:1269 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 4 16 theme key 421:423 arg1 basis 435:439 the key molecular basis 417:439 the key molecular basis of attenuation 417:454 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35336854 6 17 from located 820:826 arg1 protein 850:856 the E protein 844:856 the E protein 844:856 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 17 from located 820:826 arg1 domain 831:836 domain II 831:839 domain II of the E protein 831:856 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 7 18 dep resulted 961:968 arg1 compared 1054:1061 compared 1054:1061 compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks 1054:1164 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 4 19 theme TMUV-FX2010 525:535 arg1 strain 542:547 the wild-type TMUV-FX2010 (FX) strain 511:547 the wild-type TMUV-FX2010 (FX) strain 511:547 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35336854 5 20 from loss 733:736 arg1 ducks 757:761 ducks 757:761 ducks 757:761 The results show that the envelope (E) protein was responsible for attenuation and loss of transmission in ducks. 35336854 7 21 theme high-mannose 982:993 arg1 glycosylation 1009:1021 an extra high-mannose type N-linked glycosylation 973:1021 an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P 973:1052 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 7 21 theme high-mannose 982:993 arg1 NLG 1024:1026 NLG 1024:1026 NLG 1024:1026 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 8 22 from attenuation 1250:1260 arg1 ducks 1265:1269 ducks 1265:1269 ducks 1265:1269 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 7 23 theme type 995:998 arg1 glycosylation 1009:1021 an extra high-mannose type N-linked glycosylation 973:1021 an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P 973:1052 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 7 23 theme type 995:998 arg1 NLG 1024:1026 NLG 1024:1026 NLG 1024:1026 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 6 24 from ducks 931:935 arg1 attenuation 882:892 attenuation 882:892 attenuation 882:892 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 24 from ducks 931:935 arg1 loss 915:918 transmissibility loss 898:918 transmissibility loss 898:918 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 0 25 theme Single 2:7 arg1 Mutation 9:16 A Single Mutation 0:16 A Single Mutation at Position 120 in the Envelope Protein 0:56 A Single Mutation at Position 120 in the Envelope Protein Attenuates Tembusu Virus in Ducks. 35336854 0 26 from Position 21:28 arg1 Mutation 9:16 A Single Mutation 0:16 A Single Mutation at Position 120 in the Envelope Protein 0:56 A Single Mutation at Position 120 in the Envelope Protein Attenuates Tembusu Virus in Ducks. 35336854 8 27 from N120 1195:1198 arg1 protein 1209:1215 the E protein 1203:1215 the E protein 1203:1215 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 8 28 theme key 1222:1224 arg1 N120 1195:1198 N120 1195:1198 N120 in the E protein 1195:1215 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 8 28 theme key 1222:1224 arg1 basis 1236:1240 a key molecular basis 1220:1240 a key molecular basis of TMUV attenuation in ducks 1220:1269 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 6 29 theme D120N 794:798 arg1 mutation 811:818 a D120N amino acid mutation 792:818 a D120N amino acid mutation located in domain II of the E protein 792:856 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 29 theme D120N 794:798 arg1 responsible 862:872 responsible 862:872 responsible 862:872 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 0 30 from Virus 77:81 arg1 Ducks 86:90 Ducks 86:90 Ducks 86:90 A Single Mutation at Position 120 in the Envelope Protein Attenuates Tembusu Virus in Ducks. 35336854 4 31 theme tissue 584:589 arg1 tropism 591:597 tissue tropism 584:597 tissue tropism 584:597 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35336854 1 32 from ducks 220:224 arg1 China 229:233 China 229:233 China 229:233 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 8 33 theme attenuation 1250:1260 arg1 N120 1195:1198 N120 1195:1198 N120 in the E protein 1195:1215 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 8 33 theme attenuation 1250:1260 arg1 basis 1236:1240 a key molecular basis 1220:1240 a key molecular basis of TMUV attenuation in ducks 1220:1269 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 7 34 dep tropism 1120:1126 arg1 the 1109:1111 the 1109:1111 the 1109:1111 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 7 35 link N-linked 1000:1007 arg1 glycosylation 1009:1021 an extra high-mannose type N-linked glycosylation 973:1021 an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P 973:1052 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 7 35 link N-linked 1000:1007 arg1 NLG 1024:1026 NLG 1024:1026 NLG 1024:1026 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 6 36 theme protein 850:856 arg1 protein 850:856 the E protein 844:856 the E protein 844:856 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 36 theme protein 850:856 arg1 domain 831:836 domain II 831:839 domain II of the E protein 831:856 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 2 37 theme wild-type 250:258 arg1 TMUV 260:263 wild-type TMUV 250:263 wild-type TMUV 250:263 Compared with wild-type TMUV, 180P was highly attenuated and lost transmissibility in ducks. 35336854 6 38 theme located 820:826 arg1 mutation 811:818 a D120N amino acid mutation 792:818 a D120N amino acid mutation located in domain II of the E protein 792:856 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 38 theme located 820:826 arg1 responsible 862:872 responsible 862:872 responsible 862:872 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 5 39 theme transmission 741:752 arg1 attenuation 717:727 attenuation 717:727 attenuation 717:727 The results show that the envelope (E) protein was responsible for attenuation and loss of transmission in ducks. 35336854 5 39 theme transmission 741:752 arg1 loss 733:736 loss 733:736 loss of transmission in ducks 733:761 The results show that the envelope (E) protein was responsible for attenuation and loss of transmission in ducks. 35336854 4 40 from viruses 482:488 arg1 background 497:506 the background 493:506 the background of the wild-type TMUV-FX2010 (FX) strain 493:547 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35336854 6 41 theme E 848:848 arg1 protein 850:856 the E protein 844:856 the E protein 844:856 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 7 42 theme D120N 942:946 arg1 substitution 948:959 The D120N substitution 938:959 The D120N substitution 938:959 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 5 43 from attenuation 717:727 arg1 ducks 757:761 ducks 757:761 ducks 757:761 The results show that the envelope (E) protein was responsible for attenuation and loss of transmission in ducks. 35336854 8 44 theme TMUV 1245:1248 arg1 attenuation 1250:1260 TMUV attenuation 1245:1260 TMUV attenuation in ducks 1245:1269 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 3 45 theme 180P 374:377 arg1 attenuation 359:369 the attenuation 355:369 the attenuation of 180P 355:377 However, the mechanism of the attenuation of 180P remains poorly understood. 35336854 7 46 gly glycosylation 1009:1021 arg1 protein 1038:1044 the E protein 1032:1044 the E protein of 180P 1032:1052 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 3 47 theme attenuation 359:369 arg1 mechanism 342:350 the mechanism 338:350 the mechanism of the attenuation of 180P 338:377 However, the mechanism of the attenuation of 180P remains poorly understood. 35336854 7 48 theme E 1036:1036 arg1 protein 1038:1044 the E protein 1032:1044 the E protein of 180P 1032:1052 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 6 49 theme Further 764:770 arg1 studies 772:778 Further studies 764:778 Further studies 764:778 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 50 theme transmissibility 898:913 arg1 loss 915:918 transmissibility loss 898:918 transmissibility loss 898:918 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 7 51 from glycosylation 1009:1021 arg1 protein 1038:1044 the E protein 1032:1044 the E protein of 180P 1032:1052 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 5 52 theme envelope 676:683 arg1 responsible 701:711 responsible 701:711 responsible 701:711 The results show that the envelope (E) protein was responsible for attenuation and loss of transmission in ducks. 35336854 5 52 theme envelope 676:683 arg1 protein 689:695 the envelope (E) protein 672:695 the envelope (E) protein 672:695 The results show that the envelope (E) protein was responsible for attenuation and loss of transmission in ducks. 35336854 8 53 theme tissue 1324:1329 arg1 tropism 1331:1337 TMUV tissue tropism 1319:1337 TMUV tissue tropism 1319:1337 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 7 54 theme TMUV 1152:1155 arg1 tropism 1120:1126 tissue tropism 1113:1126 tissue tropism 1113:1126 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 7 54 theme TMUV 1152:1155 arg1 transmissibility 1132:1147 transmissibility 1132:1147 transmissibility 1132:1147 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 6 55 dep attenuation 882:892 arg1 the 878:880 the 878:880 the 878:880 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 56 from attenuation 882:892 arg1 ducks 931:935 ducks 931:935 ducks 931:935 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 8 57 theme NLG 1312:1314 arg1 role 1304:1307 the role 1300:1307 the role of NLG in TMUV tissue tropism and transmissibility 1300:1358 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 1 58 dep vaccine 137:143 arg1 FX2010-180P 145:155 FX2010-180P 145:155 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) 93:162 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 1 58 dep vaccine 137:143 arg1 180P 158:161 180P 158:161 180P 158:161 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 1 59 theme live 95:98 arg1 vaccine 137:143 A live attenuated duck Tembusu virus (TMUV) vaccine 93:143 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) 93:162 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 4 60 theme mutant 475:480 arg1 viruses 482:488 chimeric and site mutant viruses 457:488 chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain 457:547 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35336854 7 61 from transmissibility 1132:1147 arg1 ducks 1160:1164 ducks 1160:1164 ducks 1160:1164 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 1 62 theme attenuated 100:109 arg1 virus 124:128 attenuated duck Tembusu virus 100:128 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) 93:162 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 1 62 theme attenuated 100:109 arg1 TMUV 131:134 TMUV 131:134 TMUV 131:134 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 6 63 theme 180P 923:926 arg1 attenuation 882:892 attenuation 882:892 attenuation 882:892 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 6 63 theme 180P 923:926 arg1 loss 915:918 transmissibility loss 898:918 transmissibility loss 898:918 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 8 64 theme TMUV 1319:1322 arg1 tropism 1331:1337 TMUV tissue tropism 1319:1337 TMUV tissue tropism 1319:1337 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 7 65 theme 180P 1049:1052 arg1 protein 1038:1044 the E protein 1032:1044 the E protein of 180P 1032:1052 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 7 66 theme N-linked 1000:1007 arg1 glycosylation 1009:1021 an extra high-mannose type N-linked glycosylation 973:1021 an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P 973:1052 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 7 66 theme N-linked 1000:1007 arg1 NLG 1024:1026 NLG 1024:1026 NLG 1024:1026 The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. 35336854 1 67 theme duck 111:114 arg1 virus 124:128 attenuated duck Tembusu virus 100:128 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) 93:162 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 1 67 theme duck 111:114 arg1 TMUV 131:134 TMUV 131:134 TMUV 131:134 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 4 68 theme FX 538:539 arg1 strain 542:547 the wild-type TMUV-FX2010 (FX) strain 511:547 the wild-type TMUV-FX2010 (FX) strain 511:547 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35336854 8 69 from role 1304:1307 arg1 transmissibility 1343:1358 transmissibility 1343:1358 transmissibility 1343:1358 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 8 69 from role 1304:1307 arg1 tropism 1331:1337 TMUV tissue tropism 1319:1337 TMUV tissue tropism 1319:1337 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 1 70 used utilized 181:188 arg2 vaccine 137:143 A live attenuated duck Tembusu virus (TMUV) vaccine 93:143 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) 93:162 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 8 71 theme new 1283:1285 arg1 insight 1287:1293 new insight 1283:1293 new insight into the role of NLG in TMUV tissue tropism and transmissibility 1283:1358 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 8 72 from basis 1236:1240 arg1 ducks 1265:1269 ducks 1265:1269 ducks 1265:1269 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 1 73 theme Tembusu 116:122 arg1 virus 124:128 attenuated duck Tembusu virus 100:128 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) 93:162 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 1 73 theme Tembusu 116:122 arg1 TMUV 131:134 TMUV 131:134 TMUV 131:134 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 6 74 from domain 831:836 arg1 located 820:826 located 820:826 located 820:826 Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. 35336854 0 75 theme Envelope 41:48 arg1 Protein 50:56 the Envelope Protein 37:56 the Envelope Protein 37:56 A Single Mutation at Position 120 in the Envelope Protein Attenuates Tembusu Virus in Ducks. 35336854 4 76 theme attenuation 444:454 arg1 basis 435:439 the key molecular basis 417:439 the key molecular basis of attenuation 417:454 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35336854 1 77 theme TMUV 201:204 arg1 infections 206:215 TMUV infections 201:215 TMUV infections 201:215 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 1 78 theme virus 124:128 arg1 vaccine 137:143 A live attenuated duck Tembusu virus (TMUV) vaccine 93:143 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) 93:162 A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. 35336854 8 79 from ducks 1265:1269 arg1 N120 1195:1198 N120 1195:1198 N120 in the E protein 1195:1215 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 8 79 from ducks 1265:1269 arg1 basis 1236:1240 a key molecular basis 1220:1240 a key molecular basis of TMUV attenuation in ducks 1220:1269 Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility. 35336854 4 80 theme strain 542:547 arg1 background 497:506 the background 493:506 the background of the wild-type TMUV-FX2010 (FX) strain 493:547 To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. 35245324 6 0 link N-linked 843:850 arg1 feature 889:895 a characteristic feature 872:895 a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects 872:971 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 6 0 link N-linked 843:850 arg1 site 866:869 a putative N-linked glycosylation site 832:869 a putative N-linked glycosylation site 832:869 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 6 1 theme non-blood 947:955 arg1 insects 965:971 certain non-blood feeding insects 939:971 certain non-blood feeding insects 939:971 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 2 2 gly glycoproteins 326:338 arg1 glycoproteins 326:338 glycoproteins 326:338 glycoproteins that play important role in iron transportation and have been widely characterized in vertebrates and insects, but poorly studied in blood-feeding mosquitoes 326:496 Transferrins are glycoproteins that play important role in iron transportation and have been widely characterized in vertebrates and insects, but poorly studied in blood-feeding mosquitoes. 35245324 2 2 gly glycoproteins 326:338 arg1 Transferrins 309:320 Transferrins 309:320 Transferrins 309:320 Transferrins are glycoproteins that play important role in iron transportation and have been widely characterized in vertebrates and insects, but poorly studied in blood-feeding mosquitoes. 35245324 6 3 theme N-linked 843:850 arg1 feature 889:895 a characteristic feature 872:895 a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects 872:971 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 6 3 theme N-linked 843:850 arg1 site 866:869 a putative N-linked glycosylation site 832:869 a putative N-linked glycosylation site 832:869 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 3 4 theme transcript 539:548 arg1 AcTrf1a 550:556 a 2102 bp long transcript AcTrf1a 524:556 a 2102 bp long transcript AcTrf1a 524:556 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 9 5 theme transcript 1470:1479 arg1 expression 1481:1490 the AcTrf1a transcript expression 1458:1490 the AcTrf1a transcript expression 1458:1490 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 5 6 theme in 698:699 arg1 analysis 708:715 A detailed in silico analysis 687:715 A detailed in silico analysis predicts AcTrf1a 687:732 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 5 6 theme in 698:699 arg1 polypeptide 767:777 624 amino acid (aa) long polypeptide 742:777 624 amino acid (aa) long polypeptide that carries transferrin domain 742:809 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 3 7 theme 1872bp 579:584 arg1 region 601:606 1872bp, and 226bp UTR region 579:606 1872bp, and 226bp UTR region 579:606 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 6 8 theme mammalian 912:920 arg1 transferrins 922:933 the mammalian transferrins 908:933 the mammalian transferrins 908:933 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 10 9 theme AcTrf1a 1611:1617 arg1 knockdown 1598:1606 RNAi-mediated knockdown 1584:1606 RNAi-mediated knockdown of AcTrf1a 1584:1617 RNAi-mediated knockdown of AcTrf1a causes a significant reduction in fecundity, confirming the important role of transferrin in oocyte maturation. 35245324 1 10 theme adverse 287:293 arg1 consequences 295:306 adverse consequences 287:306 adverse consequences 287:306 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 10 11 theme important 1679:1687 arg1 role 1689:1692 the important role 1675:1692 the important role of transferrin in oocyte maturation 1675:1728 RNAi-mediated knockdown of AcTrf1a causes a significant reduction in fecundity, confirming the important role of transferrin in oocyte maturation. 35245324 3 12 theme UTR 597:599 arg1 region 601:606 1872bp, and 226bp UTR region 579:606 1872bp, and 226bp UTR region 579:606 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 9 13 theme reproductive 1526:1537 arg1 fecundity 1539:1547 the reproductive fecundity 1522:1547 the reproductive fecundity of gravid adult female mosquitoes 1522:1581 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 5 14 theme acid 752:755 arg1 analysis 708:715 A detailed in silico analysis 687:715 A detailed in silico analysis predicts AcTrf1a 687:732 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 5 14 theme acid 752:755 arg1 polypeptide 767:777 624 amino acid (aa) long polypeptide 742:777 624 amino acid (aa) long polypeptide that carries transferrin domain 742:809 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 3 15 theme putative 618:625 arg1 protein 647:653 putative transferrin homolog protein 618:653 putative transferrin homolog protein from mosquito An 618:670 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 7 16 theme N-terminal 1058:1067 arg1 transferrin 1081:1091 the transferrin 1077:1091 the transferrin 1077:1091 Structure modelling prediction confirms the presence of an iron-binding site at the N-terminal lobe of the transferrin. 35245324 7 16 theme N-terminal 1058:1067 arg1 lobe 1069:1072 the N-terminal lobe 1054:1072 the N-terminal lobe of the transferrin 1054:1091 Structure modelling prediction confirms the presence of an iron-binding site at the N-terminal lobe of the transferrin. 35245324 1 17 theme concentration 239:251 arg1 alteration 216:225 any alteration 212:225 any alteration of the iron concentration (i.e. deficit or excess) 212:276 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 8 18 theme exogenous 1333:1341 arg1 challenge 1353:1361 exogenous bacterial challenge 1333:1361 exogenous bacterial challenge 1333:1361 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 11 19 theme mosquito 1901:1908 arg1 outcome 1923:1929 the mosquito reproductive outcome 1897:1929 the mosquito reproductive outcome 1897:1929 CONCLUSION All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome. 35245324 9 20 theme adult 1559:1563 arg1 mosquitoes 1572:1581 gravid adult female mosquitoes 1552:1581 gravid adult female mosquitoes 1552:1581 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 7 21 theme iron-binding 1033:1044 arg1 site 1046:1049 an iron-binding site 1030:1049 an iron-binding site 1030:1049 Structure modelling prediction confirms the presence of an iron-binding site at the N-terminal lobe of the transferrin. 35245324 9 22 theme mosquitoes 1572:1581 arg1 fecundity 1539:1547 the reproductive fecundity 1522:1547 the reproductive fecundity of gravid adult female mosquitoes 1522:1581 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 10 23 from role 1689:1692 arg1 maturation 1719:1728 oocyte maturation 1712:1728 oocyte maturation 1712:1728 RNAi-mediated knockdown of AcTrf1a causes a significant reduction in fecundity, confirming the important role of transferrin in oocyte maturation. 35245324 3 24 theme homolog 639:645 arg1 protein 647:653 putative transferrin homolog protein 618:653 putative transferrin homolog protein from mosquito An 618:670 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 5 25 contain carries 784:790 arg2 domain 804:809 transferrin domain 792:809 transferrin domain 792:809 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 5 25 contain carries 784:790 arg1 analysis 708:715 A detailed in silico analysis 687:715 A detailed in silico analysis predicts AcTrf1a 687:732 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 5 25 contain carries 784:790 arg1 polypeptide 767:777 624 amino acid (aa) long polypeptide 742:777 624 amino acid (aa) long polypeptide that carries transferrin domain 742:809 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 5 26 theme transferrin 792:802 arg1 domain 804:809 transferrin domain 792:809 transferrin domain 792:809 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 9 27 from concentration 1425:1437 arg1 supplementation 1392:1406 non-heme iron supplementation 1378:1406 non-heme iron supplementation of FeCl3 at 1 mM concentration 1378:1437 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 5 28 theme aa 758:759 arg1 analysis 708:715 A detailed in silico analysis 687:715 A detailed in silico analysis predicts AcTrf1a 687:732 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 5 28 theme aa 758:759 arg1 polypeptide 767:777 624 amino acid (aa) long polypeptide 742:777 624 amino acid (aa) long polypeptide that carries transferrin domain 742:809 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 1 29 theme optimal 156:162 arg1 homeostasis 178:188 optimal physiological homeostasis 156:188 optimal physiological homeostasis of every organism 156:206 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 5 30 theme long 762:765 arg1 analysis 708:715 A detailed in silico analysis 687:715 A detailed in silico analysis predicts AcTrf1a 687:732 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 5 30 theme long 762:765 arg1 polypeptide 767:777 624 amino acid (aa) long polypeptide 742:777 624 amino acid (aa) long polypeptide that carries transferrin domain 742:809 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 7 31 theme Structure 974:982 arg1 prediction 994:1003 Structure modelling prediction 974:1003 Structure modelling prediction 974:1003 Structure modelling prediction confirms the presence of an iron-binding site at the N-terminal lobe of the transferrin. 35245324 2 32 theme blood-feeding 473:485 arg1 mosquitoes 487:496 blood-feeding mosquitoes 473:496 blood-feeding mosquitoes 473:496 Transferrins are glycoproteins that play important role in iron transportation and have been widely characterized in vertebrates and insects, but poorly studied in blood-feeding mosquitoes. 35245324 0 33 theme Functional 0:9 arg1 disruption 11:20 Functional disruption 0:20 Functional disruption of transferrin expression 0:46 Functional disruption of transferrin expression alters reproductive physiology in Anopheles culicifacies. 35245324 9 34 theme iron 1387:1390 arg1 supplementation 1392:1406 non-heme iron supplementation 1378:1406 non-heme iron supplementation of FeCl3 at 1 mM concentration 1378:1437 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 1 35 theme Iron 117:120 arg1 metabolism 122:131 BACKGROUND Iron metabolism 106:131 BACKGROUND Iron metabolism 106:131 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 8 36 dep altered 1285:1291 arg1 enhanced 1294:1301 enhanced 1294:1301 enhanced 1294:1301 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 11 37 dep CONCLUSION 1731:1740 arg1 advocate 1767:1774 advocate 1767:1774 advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome 1767:1929 CONCLUSION All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome. 35245324 8 38 theme expression 1119:1128 arg1 analysis 1130:1137 Our spatial and temporal expression analysis 1094:1137 Our spatial and temporal expression analysis under altered pathophysiological conditions 1094:1181 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 6 39 theme most 900:903 arg1 feature 889:895 a characteristic feature 872:895 a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects 872:971 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 6 39 theme most 900:903 arg1 site 866:869 a putative N-linked glycosylation site 832:869 a putative N-linked glycosylation site 832:869 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 0 40 theme expression 37:46 arg1 disruption 11:20 Functional disruption 0:20 Functional disruption of transferrin expression 0:46 Functional disruption of transferrin expression alters reproductive physiology in Anopheles culicifacies. 35245324 11 41 theme detailed 1781:1788 arg1 characterization 1790:1805 detailed characterization 1781:1805 detailed characterization of newly identified AcTrf1a transcript 1781:1844 CONCLUSION All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome. 35245324 2 42 theme iron 368:371 arg1 transportation 373:386 iron transportation 368:386 iron transportation 368:386 Transferrins are glycoproteins that play important role in iron transportation and have been widely characterized in vertebrates and insects, but poorly studied in blood-feeding mosquitoes. 35245324 0 43 theme reproductive 55:66 arg1 physiology 68:77 reproductive physiology 55:77 reproductive physiology in Anopheles culicifacies 55:103 Functional disruption of transferrin expression alters reproductive physiology in Anopheles culicifacies. 35245324 9 44 theme mM 1422:1423 arg1 concentration 1425:1437 1 mM concentration 1420:1437 1 mM concentration 1420:1437 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 8 45 theme pathophysiological 1153:1170 arg1 conditions 1172:1181 altered pathophysiological conditions 1145:1181 altered pathophysiological conditions 1145:1181 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 10 46 theme RNAi-mediated 1584:1596 arg1 knockdown 1598:1606 RNAi-mediated knockdown 1584:1606 RNAi-mediated knockdown of AcTrf1a 1584:1617 RNAi-mediated knockdown of AcTrf1a causes a significant reduction in fecundity, confirming the important role of transferrin in oocyte maturation. 35245324 11 47 theme transcript 1835:1844 arg1 characterization 1790:1805 detailed characterization 1781:1805 detailed characterization of newly identified AcTrf1a transcript 1781:1844 CONCLUSION All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome. 35245324 3 48 dep mosquito 660:667 arg1 An 669:670 An 669:670 An 669:670 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 10 49 theme significant 1628:1638 arg1 reduction 1640:1648 a significant reduction 1626:1648 a significant reduction in fecundity 1626:1661 RNAi-mediated knockdown of AcTrf1a causes a significant reduction in fecundity, confirming the important role of transferrin in oocyte maturation. 35245324 11 50 theme identified 1816:1825 arg1 transcript 1835:1844 newly identified AcTrf1a transcript 1810:1844 newly identified AcTrf1a transcript 1810:1844 CONCLUSION All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome. 35245324 6 51 theme feeding 957:963 arg1 insects 965:971 certain non-blood feeding insects 939:971 certain non-blood feeding insects 939:971 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 3 52 theme long 534:537 arg1 AcTrf1a 550:556 a 2102 bp long transcript AcTrf1a 524:556 a 2102 bp long transcript AcTrf1a 524:556 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 9 53 theme AcTrf1a 1462:1468 arg1 expression 1481:1490 the AcTrf1a transcript expression 1458:1490 the AcTrf1a transcript expression 1458:1490 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 6 54 theme certain 939:945 arg1 insects 965:971 certain non-blood feeding insects 939:971 certain non-blood feeding insects 939:971 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 3 55 from mosquito 660:667 arg1 protein 647:653 putative transferrin homolog protein 618:653 putative transferrin homolog protein from mosquito An 618:670 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 3 56 with AcTrf1a 550:556 arg1 CDS 572:574 complete CDS 563:574 complete CDS of 1872bp, and 226bp UTR region 563:606 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 6 57 theme putative 834:841 arg1 feature 889:895 a characteristic feature 872:895 a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects 872:971 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 6 57 theme putative 834:841 arg1 site 866:869 a putative N-linked glycosylation site 832:869 a putative N-linked glycosylation site 832:869 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 3 58 theme complete 563:570 arg1 CDS 572:574 complete CDS 563:574 complete CDS of 1872bp, and 226bp UTR region 563:606 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 1 59 theme organism 199:206 arg1 homeostasis 178:188 optimal physiological homeostasis 156:188 optimal physiological homeostasis of every organism 156:206 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 8 60 theme fat-body 1234:1241 arg1 ovary 1244:1248 the fat-body, ovary 1230:1248 ovary 1244:1248 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 11 61 dep results 1759:1765 arg1 All 1742:1744 All 1742:1744 All 1742:1744 CONCLUSION All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome. 35245324 3 62 theme 226bp 591:595 arg1 region 601:606 1872bp, and 226bp UTR region 579:606 1872bp, and 226bp UTR region 579:606 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 11 63 theme AcTrf1a 1827:1833 arg1 transcript 1835:1844 newly identified AcTrf1a transcript 1810:1844 newly identified AcTrf1a transcript 1810:1844 CONCLUSION All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome. 35245324 1 64 dep deficit 259:265 arg1 i.e. 254:257 i.e. 254:257 i.e. 254:257 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 8 65 theme blood 1310:1314 arg1 meal 1316:1319 blood meal uptake 1310:1326 blood meal uptake 1310:1326 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 10 66 theme oocyte 1712:1717 arg1 maturation 1719:1728 oocyte maturation 1712:1728 oocyte maturation 1712:1728 RNAi-mediated knockdown of AcTrf1a causes a significant reduction in fecundity, confirming the important role of transferrin in oocyte maturation. 35245324 5 67 theme amino 746:750 arg1 analysis 708:715 A detailed in silico analysis 687:715 A detailed in silico analysis predicts AcTrf1a 687:732 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 5 67 theme amino 746:750 arg1 polypeptide 767:777 624 amino acid (aa) long polypeptide 742:777 624 amino acid (aa) long polypeptide that carries transferrin domain 742:809 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 1 68 theme iron 234:237 arg1 concentration 239:251 the iron concentration 230:251 the iron concentration 230:251 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 10 69 theme transferrin 1697:1707 arg1 role 1689:1692 the important role 1675:1692 the important role of transferrin in oocyte maturation 1675:1728 RNAi-mediated knockdown of AcTrf1a causes a significant reduction in fecundity, confirming the important role of transferrin in oocyte maturation. 35245324 7 70 theme transferrin 1081:1091 arg1 transferrin 1081:1091 the transferrin 1077:1091 the transferrin 1077:1091 Structure modelling prediction confirms the presence of an iron-binding site at the N-terminal lobe of the transferrin. 35245324 7 70 theme transferrin 1081:1091 arg1 lobe 1069:1072 the N-terminal lobe 1054:1072 the N-terminal lobe of the transferrin 1054:1091 Structure modelling prediction confirms the presence of an iron-binding site at the N-terminal lobe of the transferrin. 35245324 3 71 theme region 601:606 arg1 CDS 572:574 complete CDS 563:574 complete CDS of 1872bp, and 226bp UTR region 563:606 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 9 72 theme gravid 1552:1557 arg1 mosquitoes 1572:1581 gravid adult female mosquitoes 1552:1581 gravid adult female mosquitoes 1552:1581 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 11 73 theme reproductive 1910:1921 arg1 outcome 1923:1929 the mosquito reproductive outcome 1897:1929 the mosquito reproductive outcome 1897:1929 CONCLUSION All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome. 35245324 1 74 contain have 282:285 arg1 alteration 216:225 any alteration 212:225 any alteration of the iron concentration (i.e. deficit or excess) 212:276 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 1 74 contain have 282:285 arg2 consequences 295:306 adverse consequences 287:306 adverse consequences 287:306 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 9 75 theme female 1565:1570 arg1 mosquitoes 1572:1581 gravid adult female mosquitoes 1552:1581 gravid adult female mosquitoes 1552:1581 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 8 76 theme bacterial 1343:1351 arg1 challenge 1353:1361 exogenous bacterial challenge 1333:1361 exogenous bacterial challenge 1333:1361 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 0 77 theme Anopheles 82:90 arg1 culicifacies 92:103 Anopheles culicifacies 82:103 Anopheles culicifacies 82:103 Functional disruption of transferrin expression alters reproductive physiology in Anopheles culicifacies. 35245324 3 78 theme transferrin 627:637 arg1 protein 647:653 putative transferrin homolog protein 618:653 putative transferrin homolog protein from mosquito An 618:670 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 35245324 7 79 theme site 1046:1049 arg1 presence 1018:1025 the presence 1014:1025 the presence of an iron-binding site 1014:1049 Structure modelling prediction confirms the presence of an iron-binding site at the N-terminal lobe of the transferrin. 35245324 1 80 theme physiological 164:176 arg1 homeostasis 178:188 optimal physiological homeostasis 156:188 optimal physiological homeostasis of every organism 156:206 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 11 81 theme unique 1873:1878 arg1 target 1880:1885 a unique target 1871:1885 a unique target to impair the mosquito reproductive outcome 1871:1929 CONCLUSION All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome. 35245324 11 81 theme unique 1873:1878 arg1 it 1865:1866 it 1865:1866 it 1865:1866 CONCLUSION All together our results advocate that detailed characterization of newly identified AcTrf1a transcript may help to select it as a unique target to impair the mosquito reproductive outcome. 35245324 0 82 from physiology 68:77 arg1 culicifacies 92:103 Anopheles culicifacies 82:103 Anopheles culicifacies 82:103 Functional disruption of transferrin expression alters reproductive physiology in Anopheles culicifacies. 35245324 8 83 theme spatial 1098:1104 arg1 analysis 1130:1137 Our spatial and temporal expression analysis 1094:1137 Our spatial and temporal expression analysis under altered pathophysiological conditions 1094:1181 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 8 84 dep meal 1316:1319 arg1 uptake 1321:1326 uptake 1321:1326 blood meal uptake 1310:1326 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 5 85 dep analysis 708:715 arg1 predicts 717:724 predicts 717:724 predicts AcTrf1a 717:732 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 6 86 gly glycosylation 852:864 arg2 feature 889:895 a characteristic feature 872:895 a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects 872:971 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 6 86 gly glycosylation 852:864 arg2 site 866:869 a putative N-linked glycosylation site 832:869 a putative N-linked glycosylation site 832:869 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 9 87 theme non-heme 1378:1385 arg1 supplementation 1392:1406 non-heme iron supplementation 1378:1406 non-heme iron supplementation of FeCl3 at 1 mM concentration 1378:1437 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 8 88 theme temporal 1110:1117 arg1 analysis 1130:1137 Our spatial and temporal expression analysis 1094:1137 Our spatial and temporal expression analysis under altered pathophysiological conditions 1094:1181 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 7 89 theme modelling 984:992 arg1 prediction 994:1003 Structure modelling prediction 974:1003 Structure modelling prediction 974:1003 Structure modelling prediction confirms the presence of an iron-binding site at the N-terminal lobe of the transferrin. 35245324 1 90 theme BACKGROUND 106:115 arg1 metabolism 122:131 BACKGROUND Iron metabolism 106:131 BACKGROUND Iron metabolism 106:131 BACKGROUND Iron metabolism is crucial to maintain optimal physiological homeostasis of every organism and any alteration of the iron concentration (i.e. deficit or excess) can have adverse consequences. 35245324 5 91 dep in 698:699 arg1 silico 701:706 silico 701:706 silico 701:706 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 0 92 theme transferrin 25:35 arg1 expression 37:46 transferrin expression 25:46 transferrin expression 25:46 Functional disruption of transferrin expression alters reproductive physiology in Anopheles culicifacies. 35245324 9 93 theme FeCl3 1411:1415 arg1 supplementation 1392:1406 non-heme iron supplementation 1378:1406 non-heme iron supplementation of FeCl3 at 1 mM concentration 1378:1437 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 8 94 theme altered 1145:1151 arg1 conditions 1172:1181 altered pathophysiological conditions 1145:1181 altered pathophysiological conditions 1145:1181 Our spatial and temporal expression analysis under altered pathophysiological conditions showed that AcTrf1a is abundantly expressed in the fat-body, ovary, and its response is significantly altered (enhanced) after blood meal uptake, and exogenous bacterial challenge. 35245324 9 95 theme 1 1420:1420 arg1 mM 1422:1423 mM 1422:1423 mM 1422:1423 Additionally, non-heme iron supplementation of FeCl3 at 1 mM concentration not only augmented the AcTrf1a transcript expression in fat-body but also enhanced the reproductive fecundity of gravid adult female mosquitoes. 35245324 6 96 theme characteristic 874:887 arg1 feature 889:895 a characteristic feature 872:895 a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects 872:971 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 6 96 theme characteristic 874:887 arg1 site 866:869 a putative N-linked glycosylation site 832:869 a putative N-linked glycosylation site 832:869 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 5 97 theme detailed 689:696 arg1 analysis 708:715 A detailed in silico analysis 687:715 A detailed in silico analysis predicts AcTrf1a 687:732 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 5 97 theme detailed 689:696 arg1 polypeptide 767:777 624 amino acid (aa) long polypeptide 742:777 624 amino acid (aa) long polypeptide that carries transferrin domain 742:809 A detailed in silico analysis predicts AcTrf1a encodes 624 amino acid (aa) long polypeptide that carries transferrin domain. 35245324 10 98 from reduction 1640:1648 arg1 fecundity 1653:1661 fecundity 1653:1661 fecundity 1653:1661 RNAi-mediated knockdown of AcTrf1a causes a significant reduction in fecundity, confirming the important role of transferrin in oocyte maturation. 35245324 2 99 theme important 350:358 arg1 role 360:363 important role 350:363 important role 350:363 Transferrins are glycoproteins that play important role in iron transportation and have been widely characterized in vertebrates and insects, but poorly studied in blood-feeding mosquitoes. 35245324 6 100 theme glycosylation 852:864 arg1 feature 889:895 a characteristic feature 872:895 a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects 872:971 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 6 100 theme glycosylation 852:864 arg1 site 866:869 a putative N-linked glycosylation site 832:869 a putative N-linked glycosylation site 832:869 AcTrf1a also showed a putative N-linked glycosylation site, a characteristic feature of most of the mammalian transferrins and certain non-blood feeding insects. 35245324 3 101 dep RESULTS 499:505 arg1 characterized 510:522 characterized 510:522 characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An 510:670 RESULTS We characterized a 2102 bp long transcript AcTrf1a with complete CDS of 1872bp, and 226bp UTR region, encoding putative transferrin homolog protein from mosquito An. 37151508 5 0 theme tag 804:806 arg1 addition 756:763 the addition 752:763 the addition of a chemically functional benzylazide tag to polyisoprenoids 752:825 Here, we describe the addition of a chemically functional benzylazide tag to polyisoprenoids. 37151508 6 1 theme responsible 972:982 arg1 system 965:970 the well-characterized system 942:970 the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly 942:1041 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 7 2 theme heptasaccharide 1284:1298 arg1 jejuni 1277:1282 the C. jejuni heptasaccharide 1270:1298 the C. jejuni heptasaccharide 1270:1298 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 9 3 theme wide 1524:1527 arg1 applications 1540:1551 applications 1540:1551 applications including the discovery of new glycan-interacting partners 1540:1610 The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners. 37151508 9 3 theme wide 1524:1527 arg1 discovery 1567:1575 the discovery 1563:1575 the discovery of new glycan-interacting partners 1563:1610 The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners. 37151508 9 3 theme wide 1524:1527 arg1 variety 1529:1535 a wide variety 1522:1535 a wide variety of applications including the discovery of new glycan-interacting partners 1522:1610 The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners. 37151508 6 4 theme well-characterized 946:963 arg1 system 965:970 the well-characterized system 942:970 the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly 942:1041 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 7 5 theme glycan 1178:1183 arg1 assembly 1185:1192 glycan assembly 1178:1192 glycan assembly 1178:1192 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 7 6 theme jejuni 1277:1282 arg1 immobilization 1252:1265 the immobilization 1248:1265 the immobilization of the C. jejuni heptasaccharide on magnetic beads 1248:1316 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 7 7 theme C. 1274:1275 arg1 jejuni 1277:1282 the C. jejuni heptasaccharide 1270:1298 the C. jejuni heptasaccharide 1270:1298 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 9 8 used used 1513:1516 arg2 methods 1487:1493 The methods 1483:1493 The methods provided 1483:1502 The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners. 37151508 7 9 theme assembly 1185:1192 arg1 cost 1170:1173 the cost 1166:1173 the cost of glycan assembly 1166:1192 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 9 10 theme new 1580:1582 arg1 partners 1603:1610 new glycan-interacting partners 1580:1610 new glycan-interacting partners 1580:1610 The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners. 37151508 1 11 theme unique 189:194 arg1 fingerprint 196:206 a unique fingerprint 187:206 a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans 187:347 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37151508 7 12 theme water-soluble 1209:1221 arg1 analogue 1223:1230 the water-soluble analogue 1205:1230 the water-soluble analogue 1205:1230 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 8 13 theme conjugated 1325:1334 arg1 beads 1336:1340 These conjugated beads 1319:1340 These conjugated beads 1319:1340 These conjugated beads are then shown to interact with soybean agglutinin, a lectin known to interact with N-acetyl-galactosamine in the C. jejuni heptasaccharide. 37151508 0 14 theme Chemoenzymatic 0:13 arg1 Preparation 15:25 Chemoenzymatic Preparation 0:25 Chemoenzymatic Preparation of a Campylobacter jejuni 0:51 Chemoenzymatic Preparation of a Campylobacter jejuni Lipid-Linked Heptasaccharide on an Azide-Linked Polyisoprenoid. 37151508 1 15 from oligosaccharides 135:150 arg1 surface 159:165 the surface 155:165 the surface of bacteria 155:177 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37151508 1 16 theme Complex 117:123 arg1 poly- 125:129 Complex poly- 117:129 Complex poly- 117:129 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37151508 2 17 theme bacterial 415:423 arg1 glycans 425:431 specific bacterial glycans 406:431 specific bacterial glycans 406:431 To discover reagents that can selectively interact with specific bacterial glycans, a system for both the chemoenzymatic preparation and immobilization of these materials would be ideal. 37151508 3 18 theme C55 598:600 arg1 bactoprenyl 617:627 the C55 polyisoprenoid bactoprenyl (or undecaprenyl) phosphate 594:655 bactoprenyl 617:627 Bacterial glycans are typically synthesized in nature on the C55 polyisoprenoid bactoprenyl (or undecaprenyl) phosphate. 37151508 2 19 theme chemoenzymatic 456:469 arg1 preparation 471:481 the chemoenzymatic preparation 452:481 the chemoenzymatic preparation 452:481 To discover reagents that can selectively interact with specific bacterial glycans, a system for both the chemoenzymatic preparation and immobilization of these materials would be ideal. 37151508 1 20 theme selective 318:326 arg1 therapeutics 294:305 therapeutics 294:305 therapeutics 294:305 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37151508 7 21 used used 1152:1155 arg2 epimerase 1130:1138 an N-acetyl-glucosamine epimerase 1106:1138 an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly 1106:1192 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 7 22 from immobilization 1252:1265 arg1 beads 1312:1316 magnetic beads 1303:1316 magnetic beads 1303:1316 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 3 23 theme polyisoprenoid 602:615 arg1 bactoprenyl 617:627 the C55 polyisoprenoid bactoprenyl (or undecaprenyl) phosphate 594:655 bactoprenyl 617:627 Bacterial glycans are typically synthesized in nature on the C55 polyisoprenoid bactoprenyl (or undecaprenyl) phosphate. 37151508 4 24 theme long-chain 672:681 arg1 isoprenoid 683:692 this long-chain isoprenoid 667:692 this long-chain isoprenoid 667:692 However, this long-chain isoprenoid can be difficult to work with in vitro. 37151508 0 25 theme jejuni 46:51 arg1 Preparation 15:25 Chemoenzymatic Preparation 0:25 Chemoenzymatic Preparation of a Campylobacter jejuni 0:51 Chemoenzymatic Preparation of a Campylobacter jejuni Lipid-Linked Heptasaccharide on an Azide-Linked Polyisoprenoid. 37151508 9 26 theme applications 1540:1551 arg1 applications 1540:1551 applications 1540:1551 applications including the discovery of new glycan-interacting partners 1540:1610 The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners. 37151508 9 26 theme applications 1540:1551 arg1 discovery 1567:1575 the discovery 1563:1575 the discovery of new glycan-interacting partners 1563:1610 The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners. 37151508 9 26 theme applications 1540:1551 arg1 variety 1529:1535 a wide variety 1522:1535 a wide variety of applications including the discovery of new glycan-interacting partners 1522:1610 The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners. 37151508 8 27 theme heptasaccharide 1466:1480 arg1 jejuni 1459:1464 the C. jejuni heptasaccharide 1452:1480 the C. jejuni heptasaccharide 1452:1480 These conjugated beads are then shown to interact with soybean agglutinin, a lectin known to interact with N-acetyl-galactosamine in the C. jejuni heptasaccharide. 37151508 1 28 theme different 211:219 arg1 strains 221:227 different strains 211:227 different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans 211:347 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37151508 1 29 theme pathogenic 232:241 arg1 microbes 257:264 pathogenic and symbiotic microbes 232:264 pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans 232:347 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37151508 0 30 theme Campylobacter 32:44 arg1 jejuni 46:51 a Campylobacter jejuni 30:51 a Campylobacter jejuni 30:51 Chemoenzymatic Preparation of a Campylobacter jejuni Lipid-Linked Heptasaccharide on an Azide-Linked Polyisoprenoid. 37151508 1 31 theme specific 332:339 arg1 glycans 341:347 specific glycans 332:347 specific glycans 332:347 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37151508 2 32 theme materials 511:519 arg1 immobilization 487:500 immobilization 487:500 immobilization 487:500 To discover reagents that can selectively interact with specific bacterial glycans, a system for both the chemoenzymatic preparation and immobilization of these materials would be ideal. 37151508 2 32 theme materials 511:519 arg1 preparation 471:481 the chemoenzymatic preparation 452:481 the chemoenzymatic preparation 452:481 To discover reagents that can selectively interact with specific bacterial glycans, a system for both the chemoenzymatic preparation and immobilization of these materials would be ideal. 37151508 6 33 theme N-linked 1009:1016 arg1 assembly 1034:1041 Campylobacter jejuni N-linked heptasaccharide assembly 988:1041 Campylobacter jejuni N-linked heptasaccharide assembly 988:1041 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 7 34 theme epimerase 1130:1138 arg1 use 1099:1101 the use 1095:1101 the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly 1095:1192 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 7 35 theme magnetic 1303:1310 arg1 beads 1312:1316 magnetic beads 1303:1316 magnetic beads 1303:1316 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 6 36 theme jejuni 1002:1007 arg1 assembly 1034:1041 Campylobacter jejuni N-linked heptasaccharide assembly 988:1041 Campylobacter jejuni N-linked heptasaccharide assembly 988:1041 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 6 37 theme benzylazide 890:900 arg1 organic-soluble 856:870 the organic-soluble 852:870 the organic-soluble 852:870 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 6 37 theme benzylazide 890:900 arg1 substrate 928:936 a substrate 926:936 a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly 926:1041 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 6 37 theme benzylazide 890:900 arg1 isoprenoid 902:911 water-soluble benzylazide isoprenoid 876:911 water-soluble benzylazide isoprenoid 876:911 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 3 38 theme undecaprenyl 633:644 arg1 phosphate 647:655 the C55 polyisoprenoid bactoprenyl (or undecaprenyl) phosphate 594:655 phosphate 647:655 Bacterial glycans are typically synthesized in nature on the C55 polyisoprenoid bactoprenyl (or undecaprenyl) phosphate. 37151508 3 39 theme Bacterial 537:545 arg1 glycans 547:553 Bacterial glycans 537:553 Bacterial glycans 537:553 Bacterial glycans are typically synthesized in nature on the C55 polyisoprenoid bactoprenyl (or undecaprenyl) phosphate. 37151508 1 40 from poly- 125:129 arg1 surface 159:165 the surface 155:165 the surface of bacteria 155:177 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37151508 6 41 theme Campylobacter 988:1000 arg1 jejuni 1002:1007 Campylobacter jejuni 988:1007 Campylobacter jejuni N-linked heptasaccharide assembly 988:1041 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 6 42 theme heptasaccharide 1018:1032 arg1 assembly 1034:1041 Campylobacter jejuni N-linked heptasaccharide assembly 988:1041 Campylobacter jejuni N-linked heptasaccharide assembly 988:1041 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 6 43 theme water-soluble 876:888 arg1 organic-soluble 856:870 the organic-soluble 852:870 the organic-soluble 852:870 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 6 43 theme water-soluble 876:888 arg1 substrate 928:936 a substrate 926:936 a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly 926:1041 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 6 43 theme water-soluble 876:888 arg1 isoprenoid 902:911 water-soluble benzylazide isoprenoid 876:911 water-soluble benzylazide isoprenoid 876:911 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 8 44 theme soybean 1374:1380 arg1 agglutinin 1382:1391 soybean agglutinin 1374:1391 soybean agglutinin 1374:1391 These conjugated beads are then shown to interact with soybean agglutinin, a lectin known to interact with N-acetyl-galactosamine in the C. jejuni heptasaccharide. 37151508 8 44 theme soybean 1374:1380 arg1 lectin 1396:1401 a lectin 1394:1401 a lectin known to interact with N-acetyl-galactosamine in the C. jejuni heptasaccharide 1394:1480 These conjugated beads are then shown to interact with soybean agglutinin, a lectin known to interact with N-acetyl-galactosamine in the C. jejuni heptasaccharide. 37151508 8 45 theme C. 1456:1457 arg1 jejuni 1459:1464 the C. jejuni heptasaccharide 1452:1480 the C. jejuni heptasaccharide 1452:1480 These conjugated beads are then shown to interact with soybean agglutinin, a lectin known to interact with N-acetyl-galactosamine in the C. jejuni heptasaccharide. 37151508 1 46 theme symbiotic 247:255 arg1 microbes 257:264 pathogenic and symbiotic microbes 232:264 pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans 232:347 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37151508 7 47 theme N-acetyl-glucosamine 1109:1128 arg1 epimerase 1130:1138 an N-acetyl-glucosamine epimerase 1106:1138 an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly 1106:1192 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 9 48 theme partners 1603:1610 arg1 discovery 1567:1575 the discovery 1563:1575 the discovery of new glycan-interacting partners 1563:1610 The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners. 37151508 1 49 theme microbes 257:264 arg1 strains 221:227 different strains 211:227 different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans 211:347 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37151508 5 50 theme functional 781:790 arg1 tag 804:806 a chemically functional benzylazide tag 768:806 a chemically functional benzylazide tag 768:806 Here, we describe the addition of a chemically functional benzylazide tag to polyisoprenoids. 37151508 9 51 theme glycan-interacting 1584:1601 arg1 partners 1603:1610 new glycan-interacting partners 1580:1610 new glycan-interacting partners 1580:1610 The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners. 37151508 2 52 theme specific 406:413 arg1 glycans 425:431 specific bacterial glycans 406:431 specific bacterial glycans 406:431 To discover reagents that can selectively interact with specific bacterial glycans, a system for both the chemoenzymatic preparation and immobilization of these materials would be ideal. 37151508 5 53 theme benzylazide 792:802 arg1 tag 804:806 a chemically functional benzylazide tag 768:806 a chemically functional benzylazide tag 768:806 Here, we describe the addition of a chemically functional benzylazide tag to polyisoprenoids. 37151508 6 54 link N-linked 1009:1016 arg1 assembly 1034:1041 Campylobacter jejuni N-linked heptasaccharide assembly 988:1041 Campylobacter jejuni N-linked heptasaccharide assembly 988:1041 We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. 37151508 7 55 theme organic-soluble 1054:1068 arg1 analogue 1070:1077 the organic-soluble analogue 1050:1077 the organic-soluble analogue 1050:1077 Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. 37151508 1 56 theme bacteria 170:177 arg1 surface 159:165 the surface 155:165 the surface of bacteria 155:177 Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. 37131834 0 0 theme glycoprotein 75:86 arg1 cap 56:58 the glycan cap 45:58 the glycan cap of Ebola virus glycoprotein 45:86 Antiviral protection by antibodies targeting the glycan cap of Ebola virus glycoprotein requires activation of the complement system. 37131834 7 1 theme mouse 1081:1085 arg1 model 1087:1091 the mouse model 1077:1091 the mouse model of EBOV infection 1077:1109 In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. 37131834 1 2 theme virus 154:158 arg1 GP 179:180 EBOV GP 174:180 EBOV GP 174:180 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 1 2 theme virus 154:158 arg1 glycoprotein 160:171 Ebola virus glycoprotein 148:171 Ebola virus glycoprotein (EBOV GP) 148:181 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 6 3 theme cells 958:962 arg1 treatment 945:953 treatment 945:953 treatment of cells with a glycosylation inhibitor 945:993 Moreover, treatment of cells with a glycosylation inhibitor increased the CDC activity, suggesting that N-linked glycans downregulate CDC. 37131834 0 4 theme virus 69:73 arg1 glycoprotein 75:86 Ebola virus glycoprotein 63:86 Ebola virus glycoprotein 63:86 Antiviral protection by antibodies targeting the glycan cap of Ebola virus glycoprotein requires activation of the complement system. 37131834 6 5 link N-linked 1039:1046 arg1 glycans 1048:1054 N-linked glycans 1039:1054 N-linked glycans 1039:1054 Moreover, treatment of cells with a glycosylation inhibitor increased the CDC activity, suggesting that N-linked glycans downregulate CDC. 37131834 5 6 theme C3 867:868 arg1 deposition 870:879 C3 deposition 867:879 C3 deposition on GP in contrast to MPER-specific mAbs that did not 867:932 Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. 37131834 1 7 theme infection 246:254 arg1 survival 256:263 infection survival 246:263 infection survival 246:263 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 7 8 theme cobra 1150:1154 arg1 factor 1162:1167 cobra venom factor 1150:1167 cobra venom factor 1150:1167 In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. 37131834 5 9 from deposition 870:879 arg1 GP 884:885 GP 884:885 GP 884:885 Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. 37131834 4 10 theme glycoprotein 733:744 arg1 GP 746:747 the viral sole glycoprotein GP 718:747 the viral sole glycoprotein GP 718:747 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 1 11 theme survival 256:263 arg1 correlate 206:214 an important correlate 193:214 an important correlate of the vaccine efficiency and infection survival 193:263 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 7 12 theme venom 1156:1160 arg1 factor 1162:1167 cobra venom factor 1150:1167 cobra venom factor 1150:1167 In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. 37131834 4 13 theme sole 728:731 arg1 GP 746:747 the viral sole glycoprotein GP 718:747 the viral sole glycoprotein GP 718:747 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 14 theme membrane-proximal 674:690 arg1 region 701:706 the membrane-proximal external region 670:706 the membrane-proximal external region (MPER) of the viral sole glycoprotein GP 670:747 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 14 theme membrane-proximal 674:690 arg1 MPER 709:712 MPER 709:712 MPER 709:712 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 7 15 theme system 1140:1145 arg1 depletion 1112:1120 depletion 1112:1120 depletion of the complement system by cobra venom factor 1112:1167 In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. 37131834 7 16 theme protection 1193:1202 arg1 impairment 1179:1188 an impairment 1176:1188 an impairment of protection exerted by GC-specific but not MPER-specific mAbs 1176:1252 In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. 37131834 5 17 theme MPER-specific 902:914 arg1 mAbs 916:919 MPER-specific mAbs 902:919 MPER-specific mAbs that did not 902:932 Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. 37131834 6 18 theme CDC 1009:1011 arg1 activity 1013:1020 the CDC activity 1005:1020 the CDC activity 1005:1020 Moreover, treatment of cells with a glycosylation inhibitor increased the CDC activity, suggesting that N-linked glycans downregulate CDC. 37131834 8 19 theme system 1306:1311 arg1 component 1329:1337 an essential component 1316:1337 an essential component of antiviral protection by antibodies targeting GC of EBOV GP 1316:1399 Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP. 37131834 8 19 theme system 1306:1311 arg1 activation 1277:1286 activation 1277:1286 activation of the complement system 1277:1311 Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP. 37131834 5 20 theme GP-expressing 839:851 arg1 line 858:861 the GP-expressing cell line 835:861 the GP-expressing cell line 835:861 Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. 37131834 2 21 theme epitope 396:402 arg1 specificities 404:416 various epitope specificities 388:416 various epitope specificities 388:416 Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. 37131834 5 22 theme mAbs 773:776 arg1 Binding 750:756 Binding 750:756 Binding of GC-specific mAbs to GP 750:782 Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. 37131834 8 23 theme complement 1295:1304 arg1 system 1306:1311 the complement system 1291:1311 the complement system 1291:1311 Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP. 37131834 0 24 gly glycoprotein 75:86 arg1 glycoprotein 75:86 Ebola virus glycoprotein 63:86 Ebola virus glycoprotein 63:86 Antiviral protection by antibodies targeting the glycan cap of Ebola virus glycoprotein requires activation of the complement system. 37131834 2 25 theme various 388:394 arg1 specificities 404:416 various epitope specificities 388:416 various epitope specificities 388:416 Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. 37131834 7 26 theme MPER-specific 1235:1247 arg1 mAbs 1249:1252 GC-specific but not MPER-specific mAbs 1215:1252 GC-specific but not MPER-specific mAbs 1215:1252 In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. 37131834 4 27 theme glycan 651:656 arg1 cap 658:660 the glycan cap 647:660 the glycan cap (GC) 647:665 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 27 theme glycan 651:656 arg1 GC 663:664 GC 663:664 GC 663:664 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 3 28 theme same 426:429 arg1 time 431:434 the same time 422:434 the same time 422:434 At the same time, the role of the complement system in antibody-mediated protection remains unclear. 37131834 0 29 theme Antiviral 0:8 arg1 protection 10:19 Antiviral protection 0:19 Antiviral protection by antibodies targeting the glycan cap of Ebola virus glycoprotein 0:86 Antiviral protection by antibodies targeting the glycan cap of Ebola virus glycoprotein requires activation of the complement system. 37131834 4 30 theme complement 547:556 arg1 activation 558:567 complement activation 547:567 complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) 547:665 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 2 31 theme Fc-mediated 302:312 arg1 effects 314:320 the Fc-mediated effects 298:320 the Fc-mediated effects 298:320 Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. 37131834 5 32 theme cell 853:856 arg1 line 858:861 the GP-expressing cell line 835:861 the GP-expressing cell line 835:861 Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. 37131834 0 33 theme system 126:131 arg1 activation 97:106 activation 97:106 activation of the complement system 97:131 Antiviral protection by antibodies targeting the glycan cap of Ebola virus glycoprotein requires activation of the complement system. 37131834 4 34 theme viral 722:726 arg1 GP 746:747 the viral sole glycoprotein GP 718:747 the viral sole glycoprotein GP 718:747 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 5 35 theme complement-dependent 792:811 arg1 CDC 827:829 CDC 827:829 CDC 827:829 Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. 37131834 5 35 theme complement-dependent 792:811 arg1 cytotoxicity 813:824 complement-dependent cytotoxicity 792:824 complement-dependent cytotoxicity (CDC) 792:830 Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. 37131834 0 36 theme complement 115:124 arg1 system 126:131 the complement system 111:131 the complement system 111:131 Antiviral protection by antibodies targeting the glycan cap of Ebola virus glycoprotein requires activation of the complement system. 37131834 8 37 theme GP 1398:1399 arg1 GC 1387:1388 GC 1387:1388 GC of EBOV GP 1387:1399 Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP. 37131834 8 38 theme essential 1319:1327 arg1 activation 1277:1286 activation 1277:1286 activation of the complement system 1277:1311 Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP. 37131834 8 38 theme essential 1319:1327 arg1 component 1329:1337 an essential component 1316:1337 an essential component of antiviral protection by antibodies targeting GC of EBOV GP 1316:1399 Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP. 37131834 3 39 theme complement 453:462 arg1 system 464:469 the complement system 449:469 the complement system 449:469 At the same time, the role of the complement system in antibody-mediated protection remains unclear. 37131834 7 40 theme infection 1101:1109 arg1 model 1087:1091 the mouse model 1077:1091 the mouse model of EBOV infection 1077:1109 In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. 37131834 1 41 dep efficiency 231:240 arg1 the 219:221 the 219:221 the 219:221 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 8 42 theme antiviral 1342:1350 arg1 protection 1352:1361 antiviral protection 1342:1361 antiviral protection by antibodies targeting GC of EBOV GP 1342:1399 Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP. 37131834 1 43 theme important 196:204 arg1 correlate 206:214 an important correlate 193:214 an important correlate of the vaccine efficiency and infection survival 193:263 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 6 44 theme N-linked 1039:1046 arg1 glycans 1048:1054 N-linked glycans 1039:1054 N-linked glycans 1039:1054 Moreover, treatment of cells with a glycosylation inhibitor increased the CDC activity, suggesting that N-linked glycans downregulate CDC. 37131834 7 45 theme EBOV 1096:1099 arg1 infection 1101:1109 EBOV infection 1096:1109 EBOV infection 1096:1109 In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. 37131834 3 46 from role 441:444 arg1 protection 492:501 antibody-mediated protection 474:501 antibody-mediated protection 474:501 At the same time, the role of the complement system in antibody-mediated protection remains unclear. 37131834 2 47 theme specificities 404:416 arg1 antibodies 374:383 antibodies 374:383 antibodies of various epitope specificities 374:416 Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. 37131834 5 48 theme GC-specific 761:771 arg1 mAbs 773:776 GC-specific mAbs 761:776 GC-specific mAbs 761:776 Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. 37131834 3 49 theme antibody-mediated 474:490 arg1 protection 492:501 antibody-mediated protection 474:501 antibody-mediated protection 474:501 At the same time, the role of the complement system in antibody-mediated protection remains unclear. 37131834 0 50 theme glycan 49:54 arg1 cap 56:58 the glycan cap 45:58 the glycan cap of Ebola virus glycoprotein 45:86 Antiviral protection by antibodies targeting the glycan cap of Ebola virus glycoprotein requires activation of the complement system. 37131834 4 51 theme representative 586:599 arg1 antibodies 612:621 representative monoclonal antibodies 586:621 representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) 586:665 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 51 theme representative 586:599 arg1 mAbs 624:627 mAbs 624:627 mAbs 624:627 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 8 52 theme protection 1352:1361 arg1 activation 1277:1286 activation 1277:1286 activation of the complement system 1277:1311 Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP. 37131834 8 52 theme protection 1352:1361 arg1 component 1329:1337 an essential component 1316:1337 an essential component of antiviral protection by antibodies targeting GC of EBOV GP 1316:1399 Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP. 37131834 4 53 theme external 692:699 arg1 region 701:706 the membrane-proximal external region 670:706 the membrane-proximal external region (MPER) of the viral sole glycoprotein GP 670:747 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 53 theme external 692:699 arg1 MPER 709:712 MPER 709:712 MPER 709:712 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 8 54 theme EBOV 1393:1396 arg1 GP 1398:1399 EBOV GP 1393:1399 EBOV GP 1393:1399 Our data suggest that activation of the complement system is an essential component of antiviral protection by antibodies targeting GC of EBOV GP. 37131834 1 55 gly glycoprotein 160:171 arg1 GP 179:180 EBOV GP 174:180 EBOV GP 174:180 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 1 55 gly glycoprotein 160:171 arg1 glycoprotein 160:171 Ebola virus glycoprotein 148:171 Ebola virus glycoprotein (EBOV GP) 148:181 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 6 56 with treatment 945:953 arg1 inhibitor 985:993 a glycosylation inhibitor 969:993 a glycosylation inhibitor 969:993 Moreover, treatment of cells with a glycosylation inhibitor increased the CDC activity, suggesting that N-linked glycans downregulate CDC. 37131834 6 57 theme glycosylation 971:983 arg1 inhibitor 985:993 a glycosylation inhibitor 969:993 a glycosylation inhibitor 969:993 Moreover, treatment of cells with a glycosylation inhibitor increased the CDC activity, suggesting that N-linked glycans downregulate CDC. 37131834 3 58 theme system 464:469 arg1 role 441:444 the role 437:444 the role of the complement system in antibody-mediated protection 437:501 At the same time, the role of the complement system in antibody-mediated protection remains unclear. 37131834 4 59 theme antibodies 612:621 arg1 antibodies 612:621 representative monoclonal antibodies 586:621 representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) 586:665 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 59 theme antibodies 612:621 arg1 groups 576:581 two groups 572:581 two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) 572:665 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 59 theme antibodies 612:621 arg1 mAbs 624:627 mAbs 624:627 mAbs 624:627 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 60 theme GP 746:747 arg1 region 701:706 the membrane-proximal external region 670:706 the membrane-proximal external region (MPER) of the viral sole glycoprotein GP 670:747 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 60 theme GP 746:747 arg1 activation 558:567 complement activation 547:567 complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) 547:665 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 60 theme GP 746:747 arg1 MPER 709:712 MPER 709:712 MPER 709:712 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 7 61 theme GC-specific 1215:1225 arg1 mAbs 1249:1252 GC-specific but not MPER-specific mAbs 1215:1252 GC-specific but not MPER-specific mAbs 1215:1252 In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. 37131834 4 62 theme monoclonal 601:610 arg1 antibodies 612:621 representative monoclonal antibodies 586:621 representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) 586:665 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 4 62 theme monoclonal 601:610 arg1 mAbs 624:627 mAbs 624:627 mAbs 624:627 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 0 63 theme Ebola 63:67 arg1 glycoprotein 75:86 Ebola virus glycoprotein 63:86 Ebola virus glycoprotein 63:86 Antiviral protection by antibodies targeting the glycan cap of Ebola virus glycoprotein requires activation of the complement system. 37131834 5 64 dep mAbs 916:919 arg1 contrast 890:897 contrast 890:897 contrast 890:897 Binding of GC-specific mAbs to GP induced complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs that did not. 37131834 1 65 theme EBOV 174:177 arg1 GP 179:180 EBOV GP 174:180 EBOV GP 174:180 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 1 65 theme EBOV 174:177 arg1 glycoprotein 160:171 Ebola virus glycoprotein 148:171 Ebola virus glycoprotein (EBOV GP) 148:181 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 1 66 theme vaccine 223:229 arg1 efficiency 231:240 vaccine efficiency 223:240 vaccine efficiency 223:240 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 4 67 gly glycoprotein 733:744 arg1 glycoprotein 733:744 the viral sole glycoprotein GP 718:747 the viral sole glycoprotein GP 718:747 In this study, we compared complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of the viral sole glycoprotein GP. 37131834 1 68 theme Ebola 148:152 arg1 GP 179:180 EBOV GP 174:180 EBOV GP 174:180 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 1 68 theme Ebola 148:152 arg1 glycoprotein 160:171 Ebola virus glycoprotein 148:171 Ebola virus glycoprotein (EBOV GP) 148:181 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37131834 7 69 theme complement 1129:1138 arg1 system 1140:1145 the complement system 1125:1145 the complement system 1125:1145 In the mouse model of EBOV infection, depletion of the complement system by cobra venom factor led to an impairment of protection exerted by GC-specific but not MPER-specific mAbs. 37131834 1 70 theme efficiency 231:240 arg1 correlate 206:214 an important correlate 193:214 an important correlate of the vaccine efficiency and infection survival 193:263 Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. 37059226 2 0 gly N-glycosylation 277:291 arg2 sites 293:297 11 N-glycosylation sites 274:297 11 N-glycosylation sites 274:297 The glycoprotein complex (GPC) of LASV is highly glycosylation-modified, with 11 N-glycosylation sites. 37059226 2 0 gly N-glycosylation 277:291 arg2 11 274:275 11 274:275 11 274:275 The glycoprotein complex (GPC) of LASV is highly glycosylation-modified, with 11 N-glycosylation sites. 37059226 0 1 theme membrane 84:91 arg1 fusion 93:98 Lassa virus glycoprotein-mediated membrane fusion 50:98 Lassa virus glycoprotein-mediated membrane fusion 50:98 Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion. 37059226 4 2 theme first 464:468 arg1 site 484:487 the first glycosylation site 460:487 the first glycosylation site 460:487 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 37059226 1 3 theme severe 154:159 arg1 fever 179:183 severe hemorrhagic Lassa fever 154:183 severe hemorrhagic Lassa fever in humans 154:193 The Lassa virus is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. 37059226 6 4 gly glycosylation 839:851 arg2 site 853:856 the key glycosylation site 831:856 the key glycosylation site on LASV GPC 831:868 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 6 5 from site 853:856 arg1 GPC 866:868 LASV GPC 861:868 LASV GPC 861:868 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 6 6 theme glycosylation 839:851 arg1 site 853:856 the key glycosylation site 831:856 the key glycosylation site on LASV GPC 831:868 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 4 7 gly glycosylation 470:482 arg2 site 484:487 the first glycosylation site 460:487 the first glycosylation site 460:487 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 37059226 6 8 theme key 835:837 arg1 site 853:856 the key glycosylation site 831:856 the key glycosylation site on LASV GPC 831:868 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 1 9 from Africa 136:141 arg1 endemic 120:126 endemic 120:126 endemic 120:126 The Lassa virus is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. 37059226 1 9 from Africa 136:141 arg1 virus 111:115 The Lassa virus 101:115 The Lassa virus 101:115 The Lassa virus is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. 37059226 6 10 theme infection 912:920 arg1 mechanism 894:902 the mechanism 890:902 the mechanism of LASV infection 890:920 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 4 11 theme GPC 610:612 arg1 expression 614:623 GPC expression 610:623 GPC expression 610:623 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 37059226 1 12 theme hemorrhagic 161:171 arg1 fever 179:183 severe hemorrhagic Lassa fever 154:183 severe hemorrhagic Lassa fever in humans 154:193 The Lassa virus is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. 37059226 3 13 theme critical 335:342 arg1 roles 344:348 critical roles 335:348 critical roles 335:348 All 11 N-linked glycan chains play critical roles in GPC cleavage, folding, receptor binding, membrane fusion, and immune evasion. 37059226 1 14 theme Lassa 173:177 arg1 fever 179:183 severe hemorrhagic Lassa fever 154:183 severe hemorrhagic Lassa fever in humans 154:193 The Lassa virus is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. 37059226 5 15 theme neutralizing 732:743 arg1 37.7H 754:758 the neutralizing antibody 37.7H 728:758 the neutralizing antibody 37.7H 728:758 Meanwhile, the pseudotype virus bearing GPCN79Q was more sensitive to the neutralizing antibody 37.7H and was attenuated in virulence. 37059226 3 16 theme N-linked 307:314 arg1 chains 323:328 All 11 N-linked glycan chains 300:328 All 11 N-linked glycan chains 300:328 All 11 N-linked glycan chains play critical roles in GPC cleavage, folding, receptor binding, membrane fusion, and immune evasion. 37059226 3 17 theme glycan 316:321 arg1 chains 323:328 All 11 N-linked glycan chains 300:328 All 11 N-linked glycan chains 300:328 All 11 N-linked glycan chains play critical roles in GPC cleavage, folding, receptor binding, membrane fusion, and immune evasion. 37059226 6 18 theme site 853:856 arg1 functions 818:826 the biological functions 803:826 the biological functions of the key glycosylation site on LASV GPC 803:868 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 3 19 theme membrane 394:401 arg1 fusion 403:408 membrane fusion 394:408 membrane fusion 394:408 All 11 N-linked glycan chains play critical roles in GPC cleavage, folding, receptor binding, membrane fusion, and immune evasion. 37059226 5 20 theme antibody 745:752 arg1 37.7H 754:758 the neutralizing antibody 37.7H 728:758 the neutralizing antibody 37.7H 728:758 Meanwhile, the pseudotype virus bearing GPCN79Q was more sensitive to the neutralizing antibody 37.7H and was attenuated in virulence. 37059226 6 21 theme LASV 907:910 arg1 infection 912:920 LASV infection 907:920 LASV infection 907:920 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 3 22 link N-linked 307:314 arg1 chains 323:328 All 11 N-linked glycan chains 300:328 All 11 N-linked glycan chains 300:328 All 11 N-linked glycan chains play critical roles in GPC cleavage, folding, receptor binding, membrane fusion, and immune evasion. 37059226 3 23 theme GPC 353:355 arg1 cleavage 357:364 GPC cleavage 353:364 GPC cleavage 353:364 All 11 N-linked glycan chains play critical roles in GPC cleavage, folding, receptor binding, membrane fusion, and immune evasion. 37059226 4 24 theme deletion 501:508 arg1 mutant 510:515 its deletion mutant 497:515 its deletion mutant (N79Q) 497:522 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 37059226 4 24 theme deletion 501:508 arg1 N79Q 518:521 N79Q 518:521 N79Q 518:521 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 37059226 1 25 from endemic 120:126 arg1 Africa 136:141 Africa 136:141 Africa 136:141 The Lassa virus is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. 37059226 1 26 theme Lassa 105:109 arg1 endemic 120:126 endemic 120:126 endemic 120:126 The Lassa virus is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. 37059226 1 26 theme Lassa 105:109 arg1 virus 111:115 The Lassa virus 101:115 The Lassa virus 101:115 The Lassa virus is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. 37059226 6 27 theme LASV 996:999 arg1 infection 1001:1009 LASV infection 996:1009 LASV infection 996:1009 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 6 28 theme biological 807:816 arg1 functions 818:826 the biological functions 803:826 the biological functions of the key glycosylation site on LASV GPC 803:868 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 2 29 theme N-glycosylation 277:291 arg1 sites 293:297 11 N-glycosylation sites 274:297 11 N-glycosylation sites 274:297 The glycoprotein complex (GPC) of LASV is highly glycosylation-modified, with 11 N-glycosylation sites. 37059226 0 30 theme site 36:39 arg1 Deletion 0:7 Deletion 0:7 Deletion of the first glycosylation site 0:39 Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion. 37059226 6 31 theme vaccines 979:986 arg1 development 953:963 the development 949:963 the development of attenuated vaccines against LASV infection 949:1009 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 3 32 theme immune 415:420 arg1 evasion 422:428 immune evasion 415:428 immune evasion 415:428 All 11 N-linked glycan chains play critical roles in GPC cleavage, folding, receptor binding, membrane fusion, and immune evasion. 37059226 0 33 theme glycosylation 22:34 arg1 site 36:39 the first glycosylation site 12:39 the first glycosylation site 12:39 Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion. 37059226 0 34 theme first 16:20 arg1 site 36:39 the first glycosylation site 12:39 the first glycosylation site 12:39 Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion. 37059226 5 35 theme pseudotype 673:682 arg1 Meanwhile 658:666 Meanwhile 658:666 Meanwhile 658:666 Meanwhile, the pseudotype virus bearing GPCN79Q was more sensitive to the neutralizing antibody 37.7H and was attenuated in virulence. 37059226 5 35 theme pseudotype 673:682 arg1 virus 684:688 the pseudotype virus 669:688 the pseudotype virus bearing GPCN79Q 669:704 Meanwhile, the pseudotype virus bearing GPCN79Q was more sensitive to the neutralizing antibody 37.7H and was attenuated in virulence. 37059226 0 36 theme Lassa 50:54 arg1 fusion 93:98 Lassa virus glycoprotein-mediated membrane fusion 50:98 Lassa virus glycoprotein-mediated membrane fusion 50:98 Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion. 37059226 4 37 theme glycosylation 470:482 arg1 site 484:487 the first glycosylation site 460:487 the first glycosylation site 460:487 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 37059226 4 38 theme receptor 640:647 arg1 binding 649:655 receptor binding 640:655 receptor binding 640:655 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 37059226 3 39 theme receptor 376:383 arg1 binding 385:391 receptor binding 376:391 receptor binding 376:391 All 11 N-linked glycan chains play critical roles in GPC cleavage, folding, receptor binding, membrane fusion, and immune evasion. 37059226 6 40 from GPC 866:868 arg1 functions 818:826 the biological functions 803:826 the biological functions of the key glycosylation site on LASV GPC 803:868 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 2 41 theme glycoprotein 200:211 arg1 GPC 222:224 GPC 222:224 GPC 222:224 The glycoprotein complex (GPC) of LASV is highly glycosylation-modified, with 11 N-glycosylation sites. 37059226 2 41 theme glycoprotein 200:211 arg1 complex 213:219 The glycoprotein complex 196:219 The glycoprotein complex (GPC) of LASV 196:233 The glycoprotein complex (GPC) of LASV is highly glycosylation-modified, with 11 N-glycosylation sites. 37059226 0 42 gly glycosylation 22:34 arg2 site 36:39 the first glycosylation site 12:39 the first glycosylation site 12:39 Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion. 37059226 2 43 gly glycoprotein 200:211 arg1 glycoprotein 200:211 The glycoprotein complex 196:219 The glycoprotein complex (GPC) of LASV 196:233 The glycoprotein complex (GPC) of LASV is highly glycosylation-modified, with 11 N-glycosylation sites. 37059226 4 44 theme enhanced 549:556 arg1 fusion 567:572 an unexpected enhanced membrane fusion 535:572 an unexpected enhanced membrane fusion 535:572 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 37059226 1 45 from fever 179:183 arg1 humans 188:193 humans 188:193 humans 188:193 The Lassa virus is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. 37059226 4 46 theme unexpected 538:547 arg1 fusion 567:572 an unexpected enhanced membrane fusion 535:572 an unexpected enhanced membrane fusion 535:572 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 37059226 0 47 theme glycoprotein-mediated 62:82 arg1 fusion 93:98 Lassa virus glycoprotein-mediated membrane fusion 50:98 Lassa virus glycoprotein-mediated membrane fusion 50:98 Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion. 37059226 6 48 theme attenuated 968:977 arg1 vaccines 979:986 attenuated vaccines 968:986 attenuated vaccines against LASV infection 968:1009 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 2 49 theme LASV 230:233 arg1 GPC 222:224 GPC 222:224 GPC 222:224 The glycoprotein complex (GPC) of LASV is highly glycosylation-modified, with 11 N-glycosylation sites. 37059226 2 49 theme LASV 230:233 arg1 complex 213:219 The glycoprotein complex 196:219 The glycoprotein complex (GPC) of LASV 196:233 The glycoprotein complex (GPC) of LASV is highly glycosylation-modified, with 11 N-glycosylation sites. 37059226 4 50 theme little 593:598 arg1 effect 600:605 little effect 593:605 little effect 593:605 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 37059226 0 51 theme virus 56:60 arg1 fusion 93:98 Lassa virus glycoprotein-mediated membrane fusion 50:98 Lassa virus glycoprotein-mediated membrane fusion 50:98 Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion. 37059226 6 52 theme LASV 861:864 arg1 GPC 866:868 LASV GPC 861:868 LASV GPC 861:868 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 6 53 from functions 818:826 arg1 GPC 866:868 LASV GPC 861:868 LASV GPC 861:868 Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection. 37059226 4 54 theme membrane 558:565 arg1 fusion 567:572 an unexpected enhanced membrane fusion 535:572 an unexpected enhanced membrane fusion 535:572 In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. 36343965 6 0 theme classical 1489:1497 arg1 inhibitors 1513:1522 two classical neuraminidase inhibitors 1485:1522 two classical neuraminidase inhibitors with different electrophoretic mobilities 1485:1564 The universal approach is successfully applied to two classical neuraminidase inhibitors with different electrophoretic mobilities. 36343965 1 1 theme quantitative 181:192 arg1 analyses 194:201 quantitative analyses 181:201 quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics 181:288 Neuraminidase inhibitors modulate infections that involve sialic acids, making quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics. 36343965 4 2 theme O-linked 1139:1146 arg1 glycans 1149:1155 serine/threonine-linked (O-linked) glycans 1114:1155 serine/threonine-linked (O-linked) glycans 1114:1155 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 5 3 theme electrophoresis 1297:1311 arg1 instrument 1313:1322 an automated capillary electrophoresis instrument 1274:1322 an automated capillary electrophoresis instrument 1274:1322 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 4 4 theme sialyllactose 1049:1061 arg1 use 1042:1044 the use 1038:1044 the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans 1038:1155 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 5 5 theme nanogel 1170:1176 arg1 scheme 1189:1194 A universal nanogel patterning scheme 1158:1194 A universal nanogel patterning scheme 1158:1194 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 4 6 link serine/threonine-linked 1114:1136 arg1 glycans 1149:1155 serine/threonine-linked (O-linked) glycans 1114:1155 serine/threonine-linked (O-linked) glycans 1114:1155 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 4 7 located observed 1102:1109 arg1 glycans 1149:1155 serine/threonine-linked (O-linked) glycans 1114:1155 serine/threonine-linked (O-linked) glycans 1114:1155 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 4 7 located observed 1102:1109 arg2 motif 1096:1100 the trisaccharide motif 1078:1100 the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans 1078:1155 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 5 8 theme enzymes 1366:1372 arg1 consumption 1351:1361 the consumption 1347:1361 the consumption of enzymes 1347:1372 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 2 9 theme enzyme 381:386 arg1 reaction 399:406 a 5 nL enzyme inhibition reaction 374:406 a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product 374:475 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 3 10 theme capillary 747:755 arg1 region 733:738 the thermally controlled region 708:738 the thermally controlled region of the capillary 708:755 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 4 11 theme electrophoresis 943:957 arg1 separation 959:968 The capillary electrophoresis separation 929:968 The capillary electrophoresis separation 929:968 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 4 12 contain contains 1069:1076 arg2 motif 1096:1100 the trisaccharide motif 1078:1100 the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans 1078:1155 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 4 12 contain contains 1069:1076 arg1 sialyllactose 1049:1061 sialyllactose 1049:1061 sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans 1049:1155 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 7 13 theme ± 1673:1673 arg1 μM 1679:1680 13 ± 3 and 5.0 ± 0.9 μM 1658:1680 μM 1679:1680 The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 μM, respectively, and 28 ± 3 and 11 ± 1 μM, respectively, for Siastatin B. 36343965 3 14 theme nanogel 876:882 arg1 step 895:898 the nanogel patterning step 872:898 the nanogel patterning step to surround the enzyme zone 872:926 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 2 15 theme 5 376:376 arg1 nL 378:379 nL 378:379 nL 378:379 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 4 16 theme capillary 933:941 arg1 electrophoresis 943:957 capillary electrophoresis 933:957 The capillary electrophoresis separation 929:968 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 2 17 from reaction 399:406 arg1 line 411:414 line 411:414 line 411:414 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 7 18 theme Siastatin 1741:1749 arg1 B 1751:1751 Siastatin B 1741:1751 Siastatin B 1741:1751 The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 μM, respectively, and 28 ± 3 and 11 ± 1 μM, respectively, for Siastatin B. 36343965 3 19 theme patterning 884:893 arg1 step 895:898 the nanogel patterning step 872:898 the nanogel patterning step to surround the enzyme zone 872:926 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 2 20 theme inhibitor 556:564 arg1 Ki 576:577 Ki 576:577 Ki 576:577 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 2 20 theme inhibitor 556:564 arg1 constant 566:573 inhibitor constant 556:573 inhibitor constant (Ki) 556:578 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 8 21 theme literature 1778:1787 arg1 reports 1789:1795 literature reports 1778:1795 literature reports 1778:1795 These values agree with literature reports and reflect the weaker inhibition anticipated for Siastatin B in comparison to DANA. 36343965 5 22 with enzymes 1245:1251 arg1 inhibitors 1258:1267 inhibitors 1258:1267 inhibitors 1258:1267 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 2 23 theme min 425:427 arg1 assay 446:450 a 5 min separation-based assay 421:450 a 5 min separation-based assay of the enzymatic product 421:475 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 4 24 theme trisaccharide 1082:1094 arg1 motif 1096:1100 the trisaccharide motif 1078:1100 the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans 1078:1155 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 7 25 theme Ki 1580:1581 arg1 ± 1661:1661 13 ± 3 and 5.0 ± 0.9 μM 1658:1680 ± 1661:1661 The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 μM, respectively, and 28 ± 3 and 11 ± 1 μM, respectively, for Siastatin B. 36343965 7 25 theme Ki 1580:1581 arg1 values 1583:1588 The IC50 and Ki values 1567:1588 values 1583:1588 The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 μM, respectively, and 28 ± 3 and 11 ± 1 μM, respectively, for Siastatin B. 36343965 2 26 theme electrophoresis 322:336 arg1 system 338:343 An automated nanogel capillary electrophoresis system 291:343 An automated nanogel capillary electrophoresis system 291:343 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 2 27 theme separation-based 429:444 arg1 assay 446:450 a 5 min separation-based assay 421:450 a 5 min separation-based assay of the enzymatic product 421:475 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 3 28 theme capillary 775:783 arg1 temperature 785:795 the capillary temperature 771:795 the capillary temperature to 37 °C. 771:805 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 5 29 theme method 1403:1408 arg1 adaption 1387:1394 adaption 1387:1394 adaption of the method to different inhibitors 1387:1432 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 1 30 theme Neuraminidase 102:114 arg1 inhibitors 116:125 Neuraminidase inhibitors 102:125 Neuraminidase inhibitors 102:125 Neuraminidase inhibitors modulate infections that involve sialic acids, making quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics. 36343965 1 31 theme inhibitory 211:220 arg1 effect 222:227 this inhibitory effect 206:227 this inhibitory effect important for selecting and designing potential therapeutics 206:288 Neuraminidase inhibitors modulate infections that involve sialic acids, making quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics. 36343965 0 32 theme Microscale 0:9 arg1 Quantification 11:24 Microscale Quantification 0:24 Microscale Quantification of the Inhibition of Neuraminidase 0:59 Microscale Quantification of the Inhibition of Neuraminidase Using Capillary Nanogel Electrophoresis. 36343965 3 33 theme Aqueous 807:813 arg1 solutions 825:833 Aqueous inhibitor solutions 807:833 Aqueous inhibitor solutions 807:833 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 3 34 theme Clostridium 609:619 arg1 perfringens 621:631 Clostridium perfringens 609:631 Clostridium perfringens 609:631 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 3 35 from perfringens 621:631 arg1 enzyme 597:602 A neuraminidase enzyme 581:602 A neuraminidase enzyme from Clostridium perfringens 581:631 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 2 36 theme 5 423:423 arg1 min 425:427 min 425:427 min 425:427 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 3 37 theme inhibitor 815:823 arg1 solutions 825:833 Aqueous inhibitor solutions 807:833 Aqueous inhibitor solutions 807:833 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 4 38 link O-linked 1139:1146 arg1 glycans 1149:1155 serine/threonine-linked (O-linked) glycans 1114:1155 serine/threonine-linked (O-linked) glycans 1114:1155 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 3 39 theme neuraminidase 583:595 arg1 enzyme 597:602 A neuraminidase enzyme 581:602 A neuraminidase enzyme from Clostridium perfringens 581:631 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 4 40 gly de-sialylated 1006:1018 arg1 product 1020:1026 the de-sialylated product 1002:1026 the de-sialylated product 1002:1026 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 2 41 theme product 469:475 arg1 assay 446:450 a 5 min separation-based assay 421:450 a 5 min separation-based assay of the enzymatic product 421:475 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 4 42 theme serine/threonine-linked 1114:1136 arg1 glycans 1149:1155 serine/threonine-linked (O-linked) glycans 1114:1155 serine/threonine-linked (O-linked) glycans 1114:1155 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 5 43 theme automated 1277:1285 arg1 electrophoresis 1297:1311 an automated capillary electrophoresis 1274:1311 an automated capillary electrophoresis instrument 1274:1322 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 6 44 theme universal 1439:1447 arg1 approach 1449:1456 The universal approach 1435:1456 The universal approach 1435:1456 The universal approach is successfully applied to two classical neuraminidase inhibitors with different electrophoretic mobilities. 36343965 6 45 theme electrophoretic 1539:1553 arg1 mobilities 1555:1564 different electrophoretic mobilities 1529:1564 different electrophoretic mobilities 1529:1564 The universal approach is successfully applied to two classical neuraminidase inhibitors with different electrophoretic mobilities. 36343965 8 46 theme weaker 1813:1818 arg1 inhibition 1820:1829 the weaker inhibition 1809:1829 the weaker inhibition anticipated for Siastatin B in comparison to DANA 1809:1879 These values agree with literature reports and reflect the weaker inhibition anticipated for Siastatin B in comparison to DANA. 36343965 5 47 theme different 1413:1421 arg1 inhibitors 1423:1432 different inhibitors 1413:1432 different inhibitors 1413:1432 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 2 48 theme enzymatic 459:467 arg1 product 469:475 the enzymatic product 455:475 the enzymatic product 455:475 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 2 49 theme inhibitory 520:529 arg1 IC50 546:549 IC50 546:549 IC50 546:549 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 2 49 theme inhibitory 520:529 arg1 inhibition 489:498 inhibition 489:498 inhibition 489:498 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 2 49 theme inhibitory 520:529 arg1 concentration 531:543 the half maximal inhibitory concentration 503:543 the half maximal inhibitory concentration (IC50) 503:550 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 3 50 dep increasing 760:769 arg1 loaded 839:844 loaded 839:844 are loaded into the capillary during the nanogel patterning step to surround the enzyme zone 835:926 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 4 51 theme de-sialylated 1006:1018 arg1 product 1020:1026 the de-sialylated product 1002:1026 the de-sialylated product 1002:1026 The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. 36343965 5 52 theme universal 1160:1168 arg1 scheme 1189:1194 A universal nanogel patterning scheme 1158:1194 A universal nanogel patterning scheme 1158:1194 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 1 53 theme effect 222:227 arg1 analyses 194:201 quantitative analyses 181:201 quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics 181:288 Neuraminidase inhibitors modulate infections that involve sialic acids, making quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics. 36343965 2 54 theme maximal 512:518 arg1 IC50 546:549 IC50 546:549 IC50 546:549 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 2 54 theme maximal 512:518 arg1 inhibition 489:498 inhibition 489:498 inhibition 489:498 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 2 54 theme maximal 512:518 arg1 concentration 531:543 the half maximal inhibitory concentration 503:543 the half maximal inhibitory concentration (IC50) 503:550 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 6 55 theme neuraminidase 1499:1511 arg1 inhibitors 1513:1522 two classical neuraminidase inhibitors 1485:1522 two classical neuraminidase inhibitors with different electrophoretic mobilities 1485:1564 The universal approach is successfully applied to two classical neuraminidase inhibitors with different electrophoretic mobilities. 36343965 0 56 theme Inhibition 33:42 arg1 Quantification 11:24 Microscale Quantification 0:24 Microscale Quantification of the Inhibition of Neuraminidase 0:59 Microscale Quantification of the Inhibition of Neuraminidase Using Capillary Nanogel Electrophoresis. 36343965 2 57 with reaction 399:406 arg1 assay 446:450 a 5 min separation-based assay 421:450 a 5 min separation-based assay of the enzymatic product 421:475 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 7 58 theme N-acetyl-2,3-dehydro-2-deoxyneuraminic 1603:1640 arg1 acid 1642:1645 N-acetyl-2,3-dehydro-2-deoxyneuraminic acid 1603:1645 N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) 1603:1652 The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 μM, respectively, and 28 ± 3 and 11 ± 1 μM, respectively, for Siastatin B. 36343965 7 58 theme N-acetyl-2,3-dehydro-2-deoxyneuraminic 1603:1640 arg1 DANA 1648:1651 DANA 1648:1651 DANA 1648:1651 The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 μM, respectively, and 28 ± 3 and 11 ± 1 μM, respectively, for Siastatin B. 36343965 5 59 theme capillary 1287:1295 arg1 electrophoresis 1297:1311 an automated capillary electrophoresis 1274:1311 an automated capillary electrophoresis instrument 1274:1322 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 6 60 theme different 1529:1537 arg1 mobilities 1555:1564 different electrophoretic mobilities 1529:1564 different electrophoretic mobilities 1529:1564 The universal approach is successfully applied to two classical neuraminidase inhibitors with different electrophoretic mobilities. 36343965 5 61 theme enzymes 1245:1251 arg1 pre-mixing 1231:1240 pre-mixing 1231:1240 pre-mixing of enzymes with inhibitors 1231:1267 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 5 62 theme patterning 1178:1187 arg1 scheme 1189:1194 A universal nanogel patterning scheme 1158:1194 A universal nanogel patterning scheme 1158:1194 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 3 63 theme tunable 678:684 arg1 nanogel 686:692 a thermally tunable nanogel 666:692 a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone 666:926 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 0 64 theme Neuraminidase 47:59 arg1 Inhibition 33:42 the Inhibition 29:42 the Inhibition of Neuraminidase 29:59 Microscale Quantification of the Inhibition of Neuraminidase Using Capillary Nanogel Electrophoresis. 36343965 6 65 with inhibitors 1513:1522 arg1 mobilities 1555:1564 different electrophoretic mobilities 1529:1564 different electrophoretic mobilities 1529:1564 The universal approach is successfully applied to two classical neuraminidase inhibitors with different electrophoretic mobilities. 36343965 2 66 theme inhibition 388:397 arg1 reaction 399:406 a 5 nL enzyme inhibition reaction 374:406 a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product 374:475 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 3 67 theme enzyme 916:921 arg1 zone 923:926 the enzyme zone 912:926 the enzyme zone 912:926 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 7 68 theme IC50 1571:1574 arg1 ± 1661:1661 13 ± 3 and 5.0 ± 0.9 μM 1658:1680 ± 1661:1661 The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 μM, respectively, and 28 ± 3 and 11 ± 1 μM, respectively, for Siastatin B. 36343965 7 68 theme IC50 1571:1574 arg1 values 1583:1588 The IC50 and Ki values 1567:1588 values 1583:1588 The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 μM, respectively, and 28 ± 3 and 11 ± 1 μM, respectively, for Siastatin B. 36343965 2 69 theme capillary 312:320 arg1 system 338:343 An automated nanogel capillary electrophoresis system 291:343 An automated nanogel capillary electrophoresis system 291:343 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 8 70 theme Siastatin 1847:1855 arg1 B 1857:1857 Siastatin B 1847:1857 Siastatin B 1847:1857 These values agree with literature reports and reflect the weaker inhibition anticipated for Siastatin B in comparison to DANA. 36343965 1 71 theme sialic 160:165 arg1 acids 167:171 sialic acids 160:171 sialic acids 160:171 Neuraminidase inhibitors modulate infections that involve sialic acids, making quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics. 36343965 2 72 theme nanogel 304:310 arg1 system 338:343 An automated nanogel capillary electrophoresis system 291:343 An automated nanogel capillary electrophoresis system 291:343 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 2 73 theme nL 378:379 arg1 reaction 399:406 a 5 nL enzyme inhibition reaction 374:406 a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product 374:475 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 1 74 theme potential 267:275 arg1 therapeutics 277:288 potential therapeutics 267:288 potential therapeutics 267:288 Neuraminidase inhibitors modulate infections that involve sialic acids, making quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics. 36343965 0 75 theme Nanogel 77:83 arg1 Electrophoresis 85:99 Capillary Nanogel Electrophoresis 67:99 Capillary Nanogel Electrophoresis 67:99 Microscale Quantification of the Inhibition of Neuraminidase Using Capillary Nanogel Electrophoresis. 36343965 3 76 theme controlled 722:731 arg1 region 733:738 the thermally controlled region 708:738 the thermally controlled region of the capillary 708:755 A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. 36343965 2 77 theme automated 294:302 arg1 system 338:343 An automated nanogel capillary electrophoresis system 291:343 An automated nanogel capillary electrophoresis system 291:343 An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). 36343965 1 78 theme important 229:237 arg1 effect 222:227 this inhibitory effect 206:227 this inhibitory effect important for selecting and designing potential therapeutics 206:288 Neuraminidase inhibitors modulate infections that involve sialic acids, making quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics. 36343965 0 79 theme Capillary 67:75 arg1 Electrophoresis 85:99 Capillary Nanogel Electrophoresis 67:99 Capillary Nanogel Electrophoresis 67:99 Microscale Quantification of the Inhibition of Neuraminidase Using Capillary Nanogel Electrophoresis. 36343965 5 80 used used 1327:1330 arg2 instrument 1313:1322 an automated capillary electrophoresis instrument 1274:1322 an automated capillary electrophoresis instrument 1274:1322 A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. 36343965 7 81 theme ± 1715:1715 arg1 μM 1719:1720 11 ± 1 μM 1712:1720 11 ± 1 μM 1712:1720 The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 μM, respectively, and 28 ± 3 and 11 ± 1 μM, respectively, for Siastatin B. 36343965 7 81 theme ± 1715:1715 arg1 ± 1661:1661 13 ± 3 and 5.0 ± 0.9 μM 1658:1680 ± 1661:1661 The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 μM, respectively, and 28 ± 3 and 11 ± 1 μM, respectively, for Siastatin B. 36190502 0 0 theme activated 128:136 arg1 cells 147:151 activated stellate cells 128:151 activated stellate cells 128:151 N-acetylglucosamine-bearing polymers mimicking O-GlcNAc-modified proteins elicit anti-fibrotic activities in myofibroblasts and activated stellate cells. 36190502 8 1 theme polymers 1627:1634 arg1 administration 1590:1603 administration 1590:1603 administration of the GlcNAc-bearing polymers into carbon tetrachloride-treated mice 1590:1673 Moreover, administration of the GlcNAc-bearing polymers into carbon tetrachloride-treated mice could ameliorate liver fibrosis. 36190502 6 2 theme tetrachloride-treated 1263:1283 arg1 mice 1285:1288 carbon tetrachloride-treated mice 1256:1288 carbon tetrachloride-treated mice 1256:1288 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 3 3 from suppression 649:659 arg1 myofibroblasts 748:761 myofibroblasts 748:761 myofibroblasts 748:761 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 5 4 theme current 913:919 arg1 study 921:925 the current study 909:925 the current study 909:925 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36190502 9 5 theme O-GlcNAc-modified 1714:1730 arg1 suppressors 1851:1861 fibrosis suppressors 1842:1861 fibrosis suppressors 1842:1861 Thus, O-GlcNAc-modified proteins leaked from dead cells can interact with myofibroblasts and activated stellate cells and function as fibrosis suppressors. 36190502 9 5 theme O-GlcNAc-modified 1714:1730 arg1 proteins 1732:1739 O-GlcNAc-modified proteins 1714:1739 O-GlcNAc-modified proteins leaked from dead cells 1714:1762 Thus, O-GlcNAc-modified proteins leaked from dead cells can interact with myofibroblasts and activated stellate cells and function as fibrosis suppressors. 36190502 4 6 theme GlcNAc-bearing 828:841 arg1 polymers 843:850 GlcNAc-bearing polymers 828:850 GlcNAc-bearing polymers 828:850 We have previously reported that O-GlcNAc-modified proteins and GlcNAc-bearing polymers could interact with cell surface vimentin and desmin. 36190502 3 7 from myofibroblasts 748:761 arg1 induction 707:715 the induction 703:715 the induction of matrix metalloprotease 1 in myofibroblasts 703:761 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 3 7 from myofibroblasts 748:761 arg1 suppression 649:659 the suppression 645:659 the suppression of α-smooth muscle actin and collagen 645:697 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 7 8 theme liver 1552:1556 arg1 fibrosis 1558:1565 the interaction exacerbated liver fibrosis 1524:1565 the interaction exacerbated liver fibrosis in the mice 1524:1577 In addition, the administration of anti-O-GlcNAc antibody to inhibit the interaction exacerbated liver fibrosis in the mice. 36190502 6 9 with interaction 1164:1174 arg1 desmin 1211:1216 desmin 1211:1216 desmin 1211:1216 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 1 10 theme O-linked 154:161 arg1 proteins 205:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins 154:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins 154:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins are post-translationally modified with GlcNAc conjugated to serine and threonine residues. 36190502 6 11 from hepatocytes 1442:1452 arg1 proteins 1416:1423 the O-GlcNAc-modified proteins 1394:1423 the O-GlcNAc-modified proteins from the damaged hepatocytes 1394:1452 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 0 12 theme stellate 138:145 arg1 cells 147:151 activated stellate cells 128:151 activated stellate cells 128:151 N-acetylglucosamine-bearing polymers mimicking O-GlcNAc-modified proteins elicit anti-fibrotic activities in myofibroblasts and activated stellate cells. 36190502 0 13 from activities 95:104 arg1 cells 147:151 activated stellate cells 128:151 activated stellate cells 128:151 N-acetylglucosamine-bearing polymers mimicking O-GlcNAc-modified proteins elicit anti-fibrotic activities in myofibroblasts and activated stellate cells. 36190502 0 13 from activities 95:104 arg1 myofibroblasts 109:122 myofibroblasts 109:122 myofibroblasts 109:122 N-acetylglucosamine-bearing polymers mimicking O-GlcNAc-modified proteins elicit anti-fibrotic activities in myofibroblasts and activated stellate cells. 36190502 5 14 theme cell 1131:1134 arg1 vimentin 1144:1151 cell surface vimentin 1131:1151 cell surface vimentin 1131:1151 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36190502 3 15 theme α-smooth 664:671 arg1 actin 680:684 α-smooth muscle actin 664:684 α-smooth muscle actin 664:684 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 3 16 theme proteins 594:601 arg1 moiety 578:583 the multivalent GlcNAc moiety 555:583 the multivalent GlcNAc moiety of these proteins 555:601 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 4 17 dep surface 877:883 arg1 desmin 898:903 desmin 898:903 desmin 898:903 We have previously reported that O-GlcNAc-modified proteins and GlcNAc-bearing polymers could interact with cell surface vimentin and desmin. 36190502 4 17 dep surface 877:883 arg1 vimentin 885:892 vimentin 885:892 vimentin 885:892 We have previously reported that O-GlcNAc-modified proteins and GlcNAc-bearing polymers could interact with cell surface vimentin and desmin. 36190502 5 18 theme moiety 974:979 arg1 structure 981:989 a multivalent GlcNAc moiety structure 953:989 a multivalent GlcNAc moiety structure of these molecules 953:1008 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36190502 5 19 theme surface 1136:1142 arg1 vimentin 1144:1151 cell surface vimentin 1131:1151 cell surface vimentin 1131:1151 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36190502 3 20 from metalloprotease 727:741 arg1 myofibroblasts 748:761 myofibroblasts 748:761 myofibroblasts 748:761 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 3 21 theme dead 506:509 arg1 cells 511:515 dead cells 506:515 dead cells 506:515 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 6 22 theme in 1297:1298 arg1 assay 1324:1328 an in situ proximity ligation assay 1294:1328 an in situ proximity ligation assay 1294:1328 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 2 23 theme physiological 350:362 arg1 signaling 429:437 Notch signaling 423:437 Notch signaling 423:437 This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. 36190502 2 23 theme physiological 350:362 arg1 functions 364:372 various physiological functions 342:372 various physiological functions such as serine and threonine phosphorylation and Notch signaling 342:437 This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. 36190502 2 23 theme physiological 350:362 arg1 phosphorylation 403:417 serine and threonine phosphorylation 382:417 serine and threonine phosphorylation 382:417 This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. 36190502 6 24 theme carbon 1256:1261 arg1 mice 1285:1288 carbon tetrachloride-treated mice 1256:1288 carbon tetrachloride-treated mice 1256:1288 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 5 25 theme molecules 1000:1008 arg1 structure 981:989 a multivalent GlcNAc moiety structure 953:989 a multivalent GlcNAc moiety structure of these molecules 953:1008 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36190502 9 26 theme stellate 1811:1818 arg1 cells 1820:1824 activated stellate cells 1801:1824 activated stellate cells 1801:1824 Thus, O-GlcNAc-modified proteins leaked from dead cells can interact with myofibroblasts and activated stellate cells and function as fibrosis suppressors. 36190502 5 27 from activities 1082:1091 arg1 myofibroblasts 1096:1109 myofibroblasts 1096:1109 myofibroblasts 1096:1109 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36190502 3 28 theme GlcNAc-bearing 521:534 arg1 polymers 536:543 GlcNAc-bearing polymers 521:543 GlcNAc-bearing polymers 521:543 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 0 29 theme N-acetylglucosamine-bearing 0:26 arg1 polymers 28:35 N-acetylglucosamine-bearing polymers 0:35 N-acetylglucosamine-bearing polymers mimicking O-GlcNAc-modified proteins 0:72 N-acetylglucosamine-bearing polymers mimicking O-GlcNAc-modified proteins elicit anti-fibrotic activities in myofibroblasts and activated stellate cells. 36190502 3 30 theme actin 680:684 arg1 induction 707:715 the induction 703:715 the induction of matrix metalloprotease 1 in myofibroblasts 703:761 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 3 30 theme actin 680:684 arg1 suppression 649:659 the suppression 645:659 the suppression of α-smooth muscle actin and collagen 645:697 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 8 31 theme liver 1692:1696 arg1 fibrosis 1698:1705 liver fibrosis 1692:1705 liver fibrosis 1692:1705 Moreover, administration of the GlcNAc-bearing polymers into carbon tetrachloride-treated mice could ameliorate liver fibrosis. 36190502 3 32 theme collagen 690:697 arg1 induction 707:715 the induction 703:715 the induction of matrix metalloprotease 1 in myofibroblasts 703:761 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 3 32 theme collagen 690:697 arg1 suppression 649:659 the suppression 645:659 the suppression of α-smooth muscle actin and collagen 645:697 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 7 33 from fibrosis 1558:1565 arg1 mice 1574:1577 the mice 1570:1577 the mice 1570:1577 In addition, the administration of anti-O-GlcNAc antibody to inhibit the interaction exacerbated liver fibrosis in the mice. 36190502 5 34 theme PI3K/Akt 1020:1027 arg1 pathway 1041:1047 PI3K/Akt and p38MAPK pathway 1020:1047 pathway 1041:1047 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36190502 0 35 theme O-GlcNAc-modified 47:63 arg1 proteins 65:72 O-GlcNAc-modified proteins 47:72 O-GlcNAc-modified proteins 47:72 N-acetylglucosamine-bearing polymers mimicking O-GlcNAc-modified proteins elicit anti-fibrotic activities in myofibroblasts and activated stellate cells. 36190502 6 36 theme stellate 1365:1372 arg1 cells 1374:1378 the activated stellate cells 1351:1378 the activated stellate cells 1351:1378 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 6 37 theme ligation 1315:1322 arg1 assay 1324:1328 an in situ proximity ligation assay 1294:1328 an in situ proximity ligation assay 1294:1328 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 3 38 theme muscle 673:678 arg1 actin 680:684 α-smooth muscle actin 664:684 α-smooth muscle actin 664:684 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 5 39 theme GlcNAc 967:972 arg1 structure 981:989 a multivalent GlcNAc moiety structure 953:989 a multivalent GlcNAc moiety structure of these molecules 953:1008 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36190502 2 40 theme threonine 393:401 arg1 phosphorylation 403:417 serine and threonine phosphorylation 382:417 serine and threonine phosphorylation 382:417 This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. 36190502 8 41 theme carbon 1641:1646 arg1 mice 1670:1673 carbon tetrachloride-treated mice 1641:1673 carbon tetrachloride-treated mice 1641:1673 Moreover, administration of the GlcNAc-bearing polymers into carbon tetrachloride-treated mice could ameliorate liver fibrosis. 36190502 2 42 theme serine 382:387 arg1 phosphorylation 403:417 serine and threonine phosphorylation 382:417 serine and threonine phosphorylation 382:417 This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. 36190502 3 43 from induction 707:715 arg1 myofibroblasts 748:761 myofibroblasts 748:761 myofibroblasts 748:761 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 3 44 theme O-GlcNAc-modified 467:483 arg1 proteins 485:492 O-GlcNAc-modified proteins 467:492 O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins 467:601 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 4 45 theme O-GlcNAc-modified 797:813 arg1 proteins 815:822 O-GlcNAc-modified proteins 797:822 O-GlcNAc-modified proteins 797:822 We have previously reported that O-GlcNAc-modified proteins and GlcNAc-bearing polymers could interact with cell surface vimentin and desmin. 36190502 10 46 theme O-GlcNAc-modified 1927:1943 arg1 proteins 1945:1952 O-GlcNAc-modified proteins 1927:1952 O-GlcNAc-modified proteins 1927:1952 Moreover, we anticipate that GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins will be applied as novel therapeutic tools for fibrosis. 36190502 6 47 theme O-GlcNAc-modified 1398:1414 arg1 proteins 1416:1423 the O-GlcNAc-modified proteins 1394:1423 the O-GlcNAc-modified proteins from the damaged hepatocytes 1394:1452 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 6 48 theme activated 1355:1363 arg1 cells 1374:1378 the activated stellate cells 1351:1378 the activated stellate cells 1351:1378 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 3 49 theme multivalent 559:569 arg1 moiety 578:583 the multivalent GlcNAc moiety 555:583 the multivalent GlcNAc moiety of these proteins 555:601 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 6 50 theme fibrotic 1238:1245 arg1 liver 1247:1251 the fibrotic liver 1234:1251 the fibrotic liver of carbon tetrachloride-treated mice 1234:1288 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 3 51 theme GlcNAc 571:576 arg1 moiety 578:583 the multivalent GlcNAc moiety 555:583 the multivalent GlcNAc moiety of these proteins 555:601 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 10 52 theme therapeutic 1979:1989 arg1 polymers 1908:1915 GlcNAc-bearing polymers 1893:1915 GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins 1893:1952 Moreover, we anticipate that GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins will be applied as novel therapeutic tools for fibrosis. 36190502 10 52 theme therapeutic 1979:1989 arg1 tools 1991:1995 novel therapeutic tools 1973:1995 novel therapeutic tools for fibrosis 1973:2008 Moreover, we anticipate that GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins will be applied as novel therapeutic tools for fibrosis. 36190502 7 53 theme exacerbated 1540:1550 arg1 fibrosis 1558:1565 the interaction exacerbated liver fibrosis 1524:1565 the interaction exacerbated liver fibrosis in the mice 1524:1577 In addition, the administration of anti-O-GlcNAc antibody to inhibit the interaction exacerbated liver fibrosis in the mice. 36190502 8 54 theme tetrachloride-treated 1648:1668 arg1 mice 1670:1673 carbon tetrachloride-treated mice 1641:1673 carbon tetrachloride-treated mice 1641:1673 Moreover, administration of the GlcNAc-bearing polymers into carbon tetrachloride-treated mice could ameliorate liver fibrosis. 36190502 6 55 theme proximity 1305:1313 arg1 assay 1324:1328 an in situ proximity ligation assay 1294:1328 an in situ proximity ligation assay 1294:1328 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 0 56 theme anti-fibrotic 81:93 arg1 activities 95:104 anti-fibrotic activities 81:104 anti-fibrotic activities in myofibroblasts and activated stellate cells 81:151 N-acetylglucosamine-bearing polymers mimicking O-GlcNAc-modified proteins elicit anti-fibrotic activities in myofibroblasts and activated stellate cells. 36190502 9 57 theme dead 1753:1756 arg1 cells 1758:1762 dead cells 1753:1762 dead cells 1753:1762 Thus, O-GlcNAc-modified proteins leaked from dead cells can interact with myofibroblasts and activated stellate cells and function as fibrosis suppressors. 36190502 7 58 theme antibody 1504:1511 arg1 administration 1472:1485 the administration 1468:1485 the administration of anti-O-GlcNAc antibody 1468:1511 In addition, the administration of anti-O-GlcNAc antibody to inhibit the interaction exacerbated liver fibrosis in the mice. 36190502 8 59 theme GlcNAc-bearing 1612:1625 arg1 polymers 1627:1634 the GlcNAc-bearing polymers 1608:1634 the GlcNAc-bearing polymers 1608:1634 Moreover, administration of the GlcNAc-bearing polymers into carbon tetrachloride-treated mice could ameliorate liver fibrosis. 36190502 7 60 theme interaction 1528:1538 arg1 fibrosis 1558:1565 the interaction exacerbated liver fibrosis 1524:1565 the interaction exacerbated liver fibrosis in the mice 1524:1577 In addition, the administration of anti-O-GlcNAc antibody to inhibit the interaction exacerbated liver fibrosis in the mice. 36190502 3 61 theme anti-fibrotic 611:623 arg1 induction 707:715 the induction 703:715 the induction of matrix metalloprotease 1 in myofibroblasts 703:761 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 3 61 theme anti-fibrotic 611:623 arg1 suppression 649:659 the suppression 645:659 the suppression of α-smooth muscle actin and collagen 645:697 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 3 61 theme anti-fibrotic 611:623 arg1 activities 625:634 anti-fibrotic activities 611:634 anti-fibrotic activities 611:634 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 3 62 theme metalloprotease 727:741 arg1 induction 707:715 the induction 703:715 the induction of matrix metalloprotease 1 in myofibroblasts 703:761 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 3 62 theme metalloprotease 727:741 arg1 suppression 649:659 the suppression 645:659 the suppression of α-smooth muscle actin and collagen 645:697 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 6 63 dep in 1297:1298 arg1 situ 1300:1303 situ 1300:1303 situ 1300:1303 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 2 64 theme various 342:348 arg1 signaling 429:437 Notch signaling 423:437 Notch signaling 423:437 This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. 36190502 2 64 theme various 342:348 arg1 functions 364:372 various physiological functions 342:372 various physiological functions such as serine and threonine phosphorylation and Notch signaling 342:437 This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. 36190502 2 64 theme various 342:348 arg1 phosphorylation 403:417 serine and threonine phosphorylation 382:417 serine and threonine phosphorylation 382:417 This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. 36190502 6 65 theme proteins 1197:1204 arg1 interaction 1164:1174 the interaction 1160:1174 the interaction of O-GlcNAc-modified proteins with desmin 1160:1216 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 2 66 theme Notch 423:427 arg1 signaling 429:437 Notch signaling 423:437 Notch signaling 423:437 This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. 36190502 9 67 theme activated 1801:1809 arg1 cells 1820:1824 activated stellate cells 1801:1824 activated stellate cells 1801:1824 Thus, O-GlcNAc-modified proteins leaked from dead cells can interact with myofibroblasts and activated stellate cells and function as fibrosis suppressors. 36190502 10 68 theme novel 1973:1977 arg1 polymers 1908:1915 GlcNAc-bearing polymers 1893:1915 GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins 1893:1952 Moreover, we anticipate that GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins will be applied as novel therapeutic tools for fibrosis. 36190502 10 68 theme novel 1973:1977 arg1 tools 1991:1995 novel therapeutic tools 1973:1995 novel therapeutic tools for fibrosis 1973:2008 Moreover, we anticipate that GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins will be applied as novel therapeutic tools for fibrosis. 36190502 5 69 theme anti-fibrotic 1068:1080 arg1 activities 1082:1091 these anti-fibrotic activities 1062:1091 these anti-fibrotic activities in myofibroblasts 1062:1109 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36190502 6 70 theme damaged 1434:1440 arg1 hepatocytes 1442:1452 the damaged hepatocytes 1430:1452 the damaged hepatocytes 1430:1452 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 5 71 theme multivalent 955:965 arg1 structure 981:989 a multivalent GlcNAc moiety structure 953:989 a multivalent GlcNAc moiety structure of these molecules 953:1008 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36190502 10 72 theme GlcNAc-bearing 1893:1906 arg1 polymers 1908:1915 GlcNAc-bearing polymers 1893:1915 GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins 1893:1952 Moreover, we anticipate that GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins will be applied as novel therapeutic tools for fibrosis. 36190502 10 72 theme GlcNAc-bearing 1893:1906 arg1 tools 1991:1995 novel therapeutic tools 1973:1995 novel therapeutic tools for fibrosis 1973:2008 Moreover, we anticipate that GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins will be applied as novel therapeutic tools for fibrosis. 36190502 1 73 mod modified 239:246 arg1 proteins 205:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins 154:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins 154:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins are post-translationally modified with GlcNAc conjugated to serine and threonine residues. 36190502 1 73 mod modified 239:246 arg3 GlcNAc 253:258 GlcNAc 253:258 GlcNAc conjugated to serine and threonine residues 253:302 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins are post-translationally modified with GlcNAc conjugated to serine and threonine residues. 36190502 7 74 theme anti-O-GlcNAc 1490:1502 arg1 antibody 1504:1511 anti-O-GlcNAc antibody 1490:1511 anti-O-GlcNAc antibody 1490:1511 In addition, the administration of anti-O-GlcNAc antibody to inhibit the interaction exacerbated liver fibrosis in the mice. 36190502 4 75 theme cell 872:875 arg1 surface 877:883 cell surface vimentin and desmin 872:903 cell surface vimentin and desmin 872:903 We have previously reported that O-GlcNAc-modified proteins and GlcNAc-bearing polymers could interact with cell surface vimentin and desmin. 36190502 6 76 theme mice 1285:1288 arg1 liver 1247:1251 the fibrotic liver 1234:1251 the fibrotic liver of carbon tetrachloride-treated mice 1234:1288 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 3 77 theme matrix 720:725 arg1 metalloprotease 727:741 matrix metalloprotease 1 720:743 matrix metalloprotease 1 in myofibroblasts 720:761 Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. 36190502 9 78 theme fibrosis 1842:1849 arg1 suppressors 1851:1861 fibrosis suppressors 1842:1861 fibrosis suppressors 1842:1861 Thus, O-GlcNAc-modified proteins leaked from dead cells can interact with myofibroblasts and activated stellate cells and function as fibrosis suppressors. 36190502 9 78 theme fibrosis 1842:1849 arg1 proteins 1732:1739 O-GlcNAc-modified proteins 1714:1739 O-GlcNAc-modified proteins leaked from dead cells 1714:1762 Thus, O-GlcNAc-modified proteins leaked from dead cells can interact with myofibroblasts and activated stellate cells and function as fibrosis suppressors. 36190502 1 79 theme -modified 195:203 arg1 proteins 205:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins 154:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins 154:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins are post-translationally modified with GlcNAc conjugated to serine and threonine residues. 36190502 6 80 theme O-GlcNAc-modified 1179:1195 arg1 proteins 1197:1204 O-GlcNAc-modified proteins 1179:1204 O-GlcNAc-modified proteins 1179:1204 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 1 81 link O-linked 154:161 arg1 proteins 205:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins 154:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins 154:212 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins are post-translationally modified with GlcNAc conjugated to serine and threonine residues. 36190502 6 82 located observed 1222:1229 arg2 interaction 1164:1174 the interaction 1160:1174 the interaction of O-GlcNAc-modified proteins with desmin 1160:1216 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 6 82 located observed 1222:1229 arg1 liver 1247:1251 the fibrotic liver 1234:1251 the fibrotic liver of carbon tetrachloride-treated mice 1234:1288 Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. 36190502 1 83 dep serine 274:279 arg1 residues 295:302 residues 295:302 residues 295:302 O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins are post-translationally modified with GlcNAc conjugated to serine and threonine residues. 36190502 5 84 theme p38MAPK 1033:1039 arg1 pathway 1041:1047 PI3K/Akt and p38MAPK pathway 1020:1047 pathway 1041:1047 In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. 36095925 8 0 from IRIF 1464:1467 arg1 cells 1486:1490 proliferating cells 1472:1490 proliferating cells 1472:1490 However, we also found that the influence of OGT on HDR and homology-directed gene targeting were dependent on RAD52, and that OGT is important for RAD52 IRIF in proliferating cells. 36095925 4 1 theme repair 662:667 arg1 pathways 669:676 repair pathways 662:676 repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing 662:782 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 2 2 theme chromosomal 371:381 arg1 breaking 383:390 chromosomal breaking 371:390 chromosomal breaking 371:390 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 4 3 theme strand 522:527 arg1 DSB 536:538 DSB 536:538 DSB 536:538 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 3 theme strand 522:527 arg1 break 529:533 DNA double strand break 511:533 DNA double strand break (DSB) reporter assays 511:555 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 5 4 theme break 855:859 arg1 end 861:863 chromosomal break end 843:863 chromosomal break end joining 843:871 In contrast, such OGT disruption did not obviously affect chromosomal break end joining, and furthermore caused an increase in homology-directed gene targeting. 36095925 2 5 dep potential 296:304 arg1 therapeutic 313:323 therapeutic 313:323 therapeutic 313:323 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 4 6 from reduction 649:657 arg1 pathways 669:676 repair pathways 662:676 repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing 662:782 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 8 7 theme OGT 1355:1357 arg1 dependent 1408:1416 dependent 1408:1416 dependent 1408:1416 However, we also found that the influence of OGT on HDR and homology-directed gene targeting were dependent on RAD52, and that OGT is important for RAD52 IRIF in proliferating cells. 36095925 8 7 theme OGT 1355:1357 arg1 influence 1342:1350 the influence 1338:1350 the influence of OGT on HDR and homology-directed gene targeting 1338:1401 However, we also found that the influence of OGT on HDR and homology-directed gene targeting were dependent on RAD52, and that OGT is important for RAD52 IRIF in proliferating cells. 36095925 6 8 theme cell 1045:1048 arg1 profiles 1056:1063 cell cycle profiles 1045:1063 cell cycle profiles 1045:1063 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 4 9 theme double 515:520 arg1 DSB 536:538 DSB 536:538 DSB 536:538 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 9 theme double 515:520 arg1 break 529:533 DNA double strand break 511:533 DNA double strand break (DSB) reporter assays 511:555 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 6 10 from reduction 983:991 arg1 survival 1007:1014 clonogenic survival 996:1014 clonogenic survival 996:1014 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 6 10 from reduction 983:991 arg1 cells 1103:1107 G1-phase cells 1094:1107 G1-phase cells 1094:1107 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 7 11 theme RAD51 1224:1228 arg1 recruitment 1230:1240 RAD51 recruitment 1224:1240 RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells 1224:1307 We also examined intermediate steps of HDR, finding no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells. 36095925 1 12 theme O-Linked 64:71 arg1 glycosylation 95:107 O-Linked β-N-acetylglucosamine glycosylation 64:107 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues 64:157 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 1 12 theme O-Linked 64:71 arg1 modification 206:217 a reversible and dynamic post-translational modification 162:217 a reversible and dynamic post-translational modification 162:217 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 1 12 theme O-Linked 64:71 arg1 O-GlcNAcylation 110:124 O-GlcNAcylation 110:124 O-GlcNAcylation 110:124 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 2 13 with combination 335:345 arg1 therapeutics 393:404 clastogenic (i.e., chromosomal breaking) therapeutics 352:404 clastogenic (i.e., chromosomal breaking) therapeutics 352:404 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 1 14 theme β-N-acetylglucosamine 73:93 arg1 glycosylation 95:107 O-Linked β-N-acetylglucosamine glycosylation 64:107 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues 64:157 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 1 14 theme β-N-acetylglucosamine 73:93 arg1 modification 206:217 a reversible and dynamic post-translational modification 162:217 a reversible and dynamic post-translational modification 162:217 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 1 14 theme β-N-acetylglucosamine 73:93 arg1 O-GlcNAcylation 110:124 O-GlcNAcylation 110:124 O-GlcNAcylation 110:124 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 6 15 from modifications 1028:1040 arg1 survival 1007:1014 clonogenic survival 996:1014 clonogenic survival 996:1014 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 6 15 from modifications 1028:1040 arg1 cells 1103:1107 G1-phase cells 1094:1107 G1-phase cells 1094:1107 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 2 16 theme potential 296:304 arg1 target 325:330 a potential cancer therapeutic target 294:330 a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics 294:404 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 6 17 theme Such 946:949 arg1 disruption 951:960 Such disruption 946:960 Such disruption in OGT 946:967 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 6 18 from disruption 951:960 arg1 OGT 965:967 OGT 965:967 OGT 965:967 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 1 19 theme post-translational 187:204 arg1 glycosylation 95:107 O-Linked β-N-acetylglucosamine glycosylation 64:107 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues 64:157 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 1 19 theme post-translational 187:204 arg1 modification 206:217 a reversible and dynamic post-translational modification 162:217 a reversible and dynamic post-translational modification 162:217 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 8 20 theme gene 1388:1391 arg1 targeting 1393:1401 homology-directed gene targeting 1370:1401 homology-directed gene targeting 1370:1401 However, we also found that the influence of OGT on HDR and homology-directed gene targeting were dependent on RAD52, and that OGT is important for RAD52 IRIF in proliferating cells. 36095925 7 21 theme intermediate 1127:1138 arg1 steps 1140:1144 intermediate steps 1127:1144 intermediate steps of HDR 1127:1151 We also examined intermediate steps of HDR, finding no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells. 36095925 7 22 theme HDR 1149:1151 arg1 steps 1140:1144 intermediate steps 1127:1144 intermediate steps of HDR 1127:1151 We also examined intermediate steps of HDR, finding no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells. 36095925 2 23 dep breaking 383:390 arg1 i.e. 365:368 i.e. 365:368 i.e. 365:368 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 2 24 from enzyme 259:264 arg1 combination 335:345 combination 335:345 combination with clastogenic (i.e., chromosomal breaking) therapeutics 335:404 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 3 25 theme O-GlcNAcylation 451:465 arg1 influence 438:446 the influence 434:446 the influence of O-GlcNAcylation on chromosomal break repair 434:493 Thus, we sought to examine the influence of O-GlcNAcylation on chromosomal break repair. 36095925 4 26 theme homology 698:705 arg1 repair 742:747 RAD51-dependent homology-directed repair 708:747 RAD51-dependent homology-directed repair (HDR) 708:753 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 26 theme homology 698:705 arg1 annealing 774:782 single strand annealing 760:782 single strand annealing 760:782 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 26 theme homology 698:705 arg1 HDR 750:752 HDR 750:752 HDR 750:752 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 26 theme homology 698:705 arg1 use 691:693 use 691:693 use of homology 691:705 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 7 27 theme end 1201:1203 arg1 resection 1205:1213 DSB end resection 1197:1213 DSB end resection 1197:1213 We also examined intermediate steps of HDR, finding no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells. 36095925 0 28 theme O-GlcNAc 0:7 arg1 transferase 9:19 O-GlcNAc transferase 0:19 O-GlcNAc transferase 0:19 O-GlcNAc transferase is important for homology-directed repair. 36095925 4 29 theme assays 550:555 arg1 assays 550:555 DNA double strand break (DSB) reporter assays 511:555 DNA double strand break (DSB) reporter assays 511:555 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 29 theme assays 550:555 arg1 set 504:506 a set 502:506 a set of DNA double strand break (DSB) reporter assays 502:555 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 7 30 from effects 1173:1179 arg1 assay 1187:1191 an assay 1184:1191 an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells 1184:1307 We also examined intermediate steps of HDR, finding no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells. 36095925 9 31 theme HDR 1550:1552 arg1 regulation 1536:1545 regulation 1536:1545 regulation of HDR that is partially linked to RAD52 function 1536:1595 Thus, we suggest that OGT is important for regulation of HDR that is partially linked to RAD52 function. 36095925 8 32 from influence 1342:1350 arg1 HDR 1362:1364 HDR 1362:1364 HDR 1362:1364 However, we also found that the influence of OGT on HDR and homology-directed gene targeting were dependent on RAD52, and that OGT is important for RAD52 IRIF in proliferating cells. 36095925 8 32 from influence 1342:1350 arg1 targeting 1393:1401 homology-directed gene targeting 1370:1401 homology-directed gene targeting 1370:1401 However, we also found that the influence of OGT on HDR and homology-directed gene targeting were dependent on RAD52, and that OGT is important for RAD52 IRIF in proliferating cells. 36095925 7 33 theme ionizing 1247:1254 arg1 radiation 1256:1264 ionizing radiation 1247:1264 ionizing radiation 1247:1264 We also examined intermediate steps of HDR, finding no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells. 36095925 4 34 theme reporter 541:548 arg1 assays 550:555 DNA double strand break (DSB) reporter assays 511:555 DNA double strand break (DSB) reporter assays 511:555 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 35 theme RAD51-dependent 708:722 arg1 repair 742:747 RAD51-dependent homology-directed repair 708:747 RAD51-dependent homology-directed repair (HDR) 708:753 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 35 theme RAD51-dependent 708:722 arg1 HDR 750:752 HDR 750:752 HDR 750:752 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 3 36 theme break 482:486 arg1 repair 488:493 chromosomal break repair 470:493 chromosomal break repair 470:493 Thus, we sought to examine the influence of O-GlcNAcylation on chromosomal break repair. 36095925 8 37 theme RAD52 1458:1462 arg1 IRIF 1464:1467 RAD52 IRIF 1458:1467 RAD52 IRIF in proliferating cells 1458:1490 However, we also found that the influence of OGT on HDR and homology-directed gene targeting were dependent on RAD52, and that OGT is important for RAD52 IRIF in proliferating cells. 36095925 2 38 theme O-GlcNAc 220:227 arg1 enzyme 259:264 the only enzyme 250:264 the only enzyme for O-GlcNAcylation 250:284 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 2 38 theme O-GlcNAc 220:227 arg1 OGT 242:244 OGT 242:244 OGT 242:244 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 2 38 theme O-GlcNAc 220:227 arg1 transferase 229:239 O-GlcNAc transferase 220:239 O-GlcNAc transferase (OGT) 220:245 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 1 39 theme dynamic 179:185 arg1 glycosylation 95:107 O-Linked β-N-acetylglucosamine glycosylation 64:107 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues 64:157 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 1 39 theme dynamic 179:185 arg1 modification 206:217 a reversible and dynamic post-translational modification 162:217 a reversible and dynamic post-translational modification 162:217 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 0 40 theme homology-directed 38:54 arg1 repair 56:61 homology-directed repair 38:61 homology-directed repair 38:61 O-GlcNAc transferase is important for homology-directed repair. 36095925 5 41 theme homology-directed 912:928 arg1 targeting 935:943 homology-directed gene targeting 912:943 homology-directed gene targeting 912:943 In contrast, such OGT disruption did not obviously affect chromosomal break end joining, and furthermore caused an increase in homology-directed gene targeting. 36095925 9 42 theme RAD52 1582:1586 arg1 function 1588:1595 RAD52 function 1582:1595 RAD52 function 1582:1595 Thus, we suggest that OGT is important for regulation of HDR that is partially linked to RAD52 function. 36095925 6 43 theme clonogenic 996:1005 arg1 survival 1007:1014 clonogenic survival 996:1014 clonogenic survival 996:1014 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 5 44 theme such 798:801 arg1 disruption 807:816 such OGT disruption 798:816 such OGT disruption 798:816 In contrast, such OGT disruption did not obviously affect chromosomal break end joining, and furthermore caused an increase in homology-directed gene targeting. 36095925 4 45 theme homology-directed 724:740 arg1 repair 742:747 RAD51-dependent homology-directed repair 708:747 RAD51-dependent homology-directed repair (HDR) 708:753 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 45 theme homology-directed 724:740 arg1 HDR 750:752 HDR 750:752 HDR 750:752 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 2 46 theme only 254:257 arg1 enzyme 259:264 the only enzyme 250:264 the only enzyme for O-GlcNAcylation 250:284 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 2 46 theme only 254:257 arg1 transferase 229:239 O-GlcNAc transferase 220:239 O-GlcNAc transferase (OGT) 220:245 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 3 47 theme chromosomal 470:480 arg1 repair 488:493 chromosomal break repair 470:493 chromosomal break repair 470:493 Thus, we sought to examine the influence of O-GlcNAcylation on chromosomal break repair. 36095925 4 48 theme break 529:533 arg1 assays 550:555 DNA double strand break (DSB) reporter assays 511:555 DNA double strand break (DSB) reporter assays 511:555 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 5 49 theme gene 930:933 arg1 targeting 935:943 homology-directed gene targeting 912:943 homology-directed gene targeting 912:943 In contrast, such OGT disruption did not obviously affect chromosomal break end joining, and furthermore caused an increase in homology-directed gene targeting. 36095925 6 50 theme cycle 1050:1054 arg1 profiles 1056:1063 cell cycle profiles 1045:1063 cell cycle profiles 1045:1063 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 8 51 theme homology-directed 1370:1386 arg1 targeting 1393:1401 homology-directed gene targeting 1370:1401 homology-directed gene targeting 1370:1401 However, we also found that the influence of OGT on HDR and homology-directed gene targeting were dependent on RAD52, and that OGT is important for RAD52 IRIF in proliferating cells. 36095925 7 52 theme proliferating 1289:1301 arg1 cells 1303:1307 proliferating cells 1289:1307 proliferating cells 1289:1307 We also examined intermediate steps of HDR, finding no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells. 36095925 6 53 from increase 1082:1089 arg1 cells 1103:1107 G1-phase cells 1094:1107 G1-phase cells 1094:1107 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 6 53 from increase 1082:1089 arg1 survival 1007:1014 clonogenic survival 996:1014 clonogenic survival 996:1014 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 9 54 attach linked 1572:1577 arg1 function 1588:1595 RAD52 function 1582:1595 RAD52 function 1582:1595 Thus, we suggest that OGT is important for regulation of HDR that is partially linked to RAD52 function. 36095925 9 54 attach linked 1572:1577 arg2 HDR 1550:1552 HDR 1550:1552 HDR that is partially linked to RAD52 function 1550:1595 Thus, we suggest that OGT is important for regulation of HDR that is partially linked to RAD52 function. 36095925 5 55 from increase 900:907 arg1 targeting 935:943 homology-directed gene targeting 912:943 homology-directed gene targeting 912:943 In contrast, such OGT disruption did not obviously affect chromosomal break end joining, and furthermore caused an increase in homology-directed gene targeting. 36095925 8 56 theme proliferating 1472:1484 arg1 cells 1486:1490 proliferating cells 1472:1490 proliferating cells 1472:1490 However, we also found that the influence of OGT on HDR and homology-directed gene targeting were dependent on RAD52, and that OGT is important for RAD52 IRIF in proliferating cells. 36095925 4 57 with depletion 576:584 arg1 molecule 626:633 a small molecule 618:633 a small molecule each 618:638 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 58 theme strand 767:772 arg1 annealing 774:782 single strand annealing 760:782 single strand annealing 760:782 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 2 59 theme clastogenic 352:362 arg1 therapeutics 393:404 clastogenic (i.e., chromosomal breaking) therapeutics 352:404 clastogenic (i.e., chromosomal breaking) therapeutics 352:404 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 36095925 6 60 theme G1-phase 1094:1101 arg1 cells 1103:1107 G1-phase cells 1094:1107 G1-phase cells 1094:1107 Such disruption in OGT also caused a reduction in clonogenic survival, as well as modifications to cell cycle profiles, particularly an increase in G1-phase cells. 36095925 4 61 theme OGT 589:591 arg1 depletion 576:584 the depletion 572:584 the depletion of OGT 572:591 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 61 theme OGT 589:591 arg1 inhibition 602:611 its inhibition 598:611 its inhibition with a small molecule each 598:638 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 62 with inhibition 602:611 arg1 molecule 626:633 a small molecule 618:633 a small molecule each 618:638 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 63 dep molecule 626:633 arg1 each 635:638 each 635:638 each 635:638 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 1 64 theme reversible 164:173 arg1 glycosylation 95:107 O-Linked β-N-acetylglucosamine glycosylation 64:107 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues 64:157 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 1 64 theme reversible 164:173 arg1 modification 206:217 a reversible and dynamic post-translational modification 162:217 a reversible and dynamic post-translational modification 162:217 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 7 65 theme DSB 1197:1199 arg1 resection 1205:1213 DSB end resection 1197:1213 DSB end resection 1197:1213 We also examined intermediate steps of HDR, finding no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells. 36095925 7 66 theme obvious 1165:1171 arg1 effects 1173:1179 no obvious effects 1162:1179 no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells 1162:1307 We also examined intermediate steps of HDR, finding no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells. 36095925 5 67 theme OGT 803:805 arg1 disruption 807:816 such OGT disruption 798:816 such OGT disruption 798:816 In contrast, such OGT disruption did not obviously affect chromosomal break end joining, and furthermore caused an increase in homology-directed gene targeting. 36095925 4 68 theme single 760:765 arg1 annealing 774:782 single strand annealing 760:782 single strand annealing 760:782 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 3 69 from influence 438:446 arg1 repair 488:493 chromosomal break repair 470:493 chromosomal break repair 470:493 Thus, we sought to examine the influence of O-GlcNAcylation on chromosomal break repair. 36095925 5 70 theme chromosomal 843:853 arg1 end 861:863 chromosomal break end 843:863 chromosomal break end joining 843:871 In contrast, such OGT disruption did not obviously affect chromosomal break end joining, and furthermore caused an increase in homology-directed gene targeting. 36095925 4 71 theme small 620:624 arg1 molecule 626:633 a small molecule 618:633 a small molecule each 618:638 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 72 theme DNA 511:513 arg1 DSB 536:538 DSB 536:538 DSB 536:538 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 4 72 theme DNA 511:513 arg1 break 529:533 DNA double strand break 511:533 DNA double strand break (DSB) reporter assays 511:555 Using a set of DNA double strand break (DSB) reporter assays, we found that the depletion of OGT, and its inhibition with a small molecule each caused a reduction in repair pathways that involve use of homology: RAD51-dependent homology-directed repair (HDR), and single strand annealing. 36095925 7 73 dep recruitment 1230:1240 arg1 induced 1266:1272 induced 1266:1272 induced foci (IRIF) in proliferating cells 1266:1307 We also examined intermediate steps of HDR, finding no obvious effects on an assay for DSB end resection, nor for RAD51 recruitment into ionizing radiation induced foci (IRIF) in proliferating cells. 36095925 1 74 dep serine 130:135 arg1 residues 150:157 residues 150:157 residues 150:157 O-Linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) to serine or threonine residues is a reversible and dynamic post-translational modification. 36095925 2 75 from target 325:330 arg1 combination 335:345 combination 335:345 combination with clastogenic (i.e., chromosomal breaking) therapeutics 335:404 O-GlcNAc transferase (OGT) is the only enzyme for O-GlcNAcylation, and is a potential cancer therapeutic target in combination with clastogenic (i.e., chromosomal breaking) therapeutics. 35513753 0 0 theme M1 83:84 arg1 macrophages 86:96 M1 macrophages 83:96 M1 macrophages 83:96 The interaction of O-GlcNAc-modified NLRX1 and IKK-α modulates IL-1β expression in M1 macrophages. 35513753 6 1 theme factor 1070:1075 arg1 kappaB 1077:1082 nuclear factor kappaB kinase-α 1062:1091 nuclear factor kappaB kinase-α (IKK-α) 1062:1099 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 6 1 theme factor 1070:1075 arg1 IKK-α 1094:1098 IKK-α 1094:1098 IKK-α 1094:1098 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 4 2 theme NLRX1 698:702 arg1 region 688:693 the nucleotide-binding domain (NBD) region 652:693 the nucleotide-binding domain (NBD) region of NLRX1 652:702 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35513753 6 3 theme kappaB 1077:1082 arg1 interaction 1019:1029 the interaction 1015:1029 the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α) 1015:1099 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 7 4 theme inflammatory 1297:1308 arg1 process 1310:1316 the inflammatory process 1293:1316 the inflammatory process in macrophages 1293:1331 Together, our results indicate that the interaction between NLRX1 and O-GlcNAcylation coordinates and modulates the inflammatory process in macrophages. 35513753 6 5 theme IL-1β 1156:1160 arg1 expression 1120:1129 the expression 1116:1129 the expression of inflammatory cytokine IL-1β in M1 macrophages 1116:1178 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 1 6 theme downstream 227:236 arg1 factors 255:261 downstream pro-inflammatory factors 227:261 downstream pro-inflammatory factors 227:261 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 6 7 theme NLRX1 918:922 arg1 stability 924:932 decreased NLRX1 stability 908:932 decreased NLRX1 stability 908:932 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 3 8 link O-linked 452:459 arg1 O-GlcNAc 482:489 O-GlcNAc 482:489 O-GlcNAc 482:489 Here, we found that NLRX1 was modified with O-linked N-acetylglucosamine (O-GlcNAc). 35513753 3 8 link O-linked 452:459 arg1 N-acetylglucosamine 461:479 O-linked N-acetylglucosamine 452:479 O-linked N-acetylglucosamine (O-GlcNAc) 452:490 Here, we found that NLRX1 was modified with O-linked N-acetylglucosamine (O-GlcNAc). 35513753 1 9 theme pro-inflammatory 238:253 arg1 factors 255:261 downstream pro-inflammatory factors 227:261 downstream pro-inflammatory factors 227:261 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 6 10 theme cytokine 1147:1154 arg1 IL-1β 1156:1160 inflammatory cytokine IL-1β 1134:1160 inflammatory cytokine IL-1β 1134:1160 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 5 11 theme OSMI-1 835:840 arg1 dose 813:816 a high dose 806:816 a high dose of OGT inhibitor OSMI-1 806:840 NLRX1 protein increased significantly after treatment with a high dose of OGT inhibitor OSMI-1. 35513753 4 12 theme domain 675:680 arg1 region 688:693 the nucleotide-binding domain (NBD) region 652:693 the nucleotide-binding domain (NBD) region of NLRX1 652:702 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35513753 7 13 from process 1310:1316 arg1 macrophages 1321:1331 macrophages 1321:1331 macrophages 1321:1331 Together, our results indicate that the interaction between NLRX1 and O-GlcNAcylation coordinates and modulates the inflammatory process in macrophages. 35513753 5 14 with treatment 791:799 arg1 dose 813:816 a high dose 806:816 a high dose of OGT inhibitor OSMI-1 806:840 NLRX1 protein increased significantly after treatment with a high dose of OGT inhibitor OSMI-1. 35513753 1 15 theme negative 138:145 arg1 regulator 147:155 a negative regulator 136:155 a negative regulator of inflammation 136:171 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 1 15 theme negative 138:145 arg1 X1 122:123 NOD-like receptor (NLR)X1 99:123 NOD-like receptor (NLR)X1 (NLRX1) 99:131 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 5 16 theme high 808:811 arg1 dose 813:816 a high dose 806:816 a high dose of OGT inhibitor OSMI-1 806:840 NLRX1 protein increased significantly after treatment with a high dose of OGT inhibitor OSMI-1. 35513753 6 17 theme decreased 908:916 arg1 stability 924:932 decreased NLRX1 stability 908:932 decreased NLRX1 stability 908:932 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 2 18 from responses 364:372 arg1 macrophages 377:387 macrophages 377:387 macrophages 377:387 However, its post-translational modification and how it participates in regulating the inflammatory responses in macrophages are still unclear. 35513753 6 19 theme M1 1165:1166 arg1 macrophages 1168:1178 M1 macrophages 1165:1178 M1 macrophages 1165:1178 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 0 20 theme O-GlcNAc-modified 19:35 arg1 NLRX1 37:41 O-GlcNAc-modified NLRX1 19:41 O-GlcNAc-modified NLRX1 19:41 The interaction of O-GlcNAc-modified NLRX1 and IKK-α modulates IL-1β expression in M1 macrophages. 35513753 4 21 theme O-GlcNAc 547:554 arg1 transferase 556:566 O-GlcNAc transferase 547:566 O-GlcNAc transferase (OGT) 547:572 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35513753 4 21 theme O-GlcNAc 547:554 arg1 OGT 569:571 OGT 569:571 OGT 569:571 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35513753 2 22 theme post-translational 277:294 arg1 modification 296:307 its post-translational modification 273:307 its post-translational modification and how it participates in regulating the inflammatory responses in macrophages 273:387 However, its post-translational modification and how it participates in regulating the inflammatory responses in macrophages are still unclear. 35513753 1 23 theme inflammation 160:171 arg1 regulator 147:155 a negative regulator 136:155 a negative regulator of inflammation 136:171 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 1 23 theme inflammation 160:171 arg1 X1 122:123 NOD-like receptor (NLR)X1 99:123 NOD-like receptor (NLR)X1 (NLRX1) 99:131 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 5 24 theme OGT 821:823 arg1 OSMI-1 835:840 OGT inhibitor OSMI-1 821:840 OGT inhibitor OSMI-1 821:840 NLRX1 protein increased significantly after treatment with a high dose of OGT inhibitor OSMI-1. 35513753 6 25 theme chase 983:987 arg1 experiments 989:999 chase experiments 983:999 chase experiments 983:999 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 6 26 theme NLRX1 883:887 arg1 ubiquitination 889:902 NLRX1 ubiquitination 883:902 NLRX1 ubiquitination 883:902 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 1 27 theme receptor 108:115 arg1 regulator 147:155 a negative regulator 136:155 a negative regulator of inflammation 136:171 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 1 27 theme receptor 108:115 arg1 NLRX1 126:130 NLRX1 126:130 NLRX1 126:130 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 1 27 theme receptor 108:115 arg1 X1 122:123 NOD-like receptor (NLR)X1 99:123 NOD-like receptor (NLR)X1 (NLRX1) 99:131 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 3 28 theme O-linked 452:459 arg1 O-GlcNAc 482:489 O-GlcNAc 482:489 O-GlcNAc 482:489 Here, we found that NLRX1 was modified with O-linked N-acetylglucosamine (O-GlcNAc). 35513753 3 28 theme O-linked 452:459 arg1 N-acetylglucosamine 461:479 O-linked N-acetylglucosamine 452:479 O-linked N-acetylglucosamine (O-GlcNAc) 452:490 Here, we found that NLRX1 was modified with O-linked N-acetylglucosamine (O-GlcNAc). 35513753 6 29 theme inflammatory 1134:1145 arg1 IL-1β 1156:1160 inflammatory cytokine IL-1β 1134:1160 inflammatory cytokine IL-1β 1134:1160 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 6 30 theme nuclear 1062:1068 arg1 kappaB 1077:1082 nuclear factor kappaB kinase-α 1062:1091 nuclear factor kappaB kinase-α (IKK-α) 1062:1099 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 6 30 theme nuclear 1062:1068 arg1 IKK-α 1094:1098 IKK-α 1094:1098 IKK-α 1094:1098 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 0 31 theme NLRX1 37:41 arg1 interaction 4:14 The interaction 0:14 The interaction of O-GlcNAc-modified NLRX1 and IKK-α 0:51 The interaction of O-GlcNAc-modified NLRX1 and IKK-α modulates IL-1β expression in M1 macrophages. 35513753 6 32 dep ubiquitination 944:957 arg1 experiments 989:999 chase experiments 983:999 chase experiments 983:999 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 0 33 from expression 69:78 arg1 macrophages 86:96 M1 macrophages 83:96 M1 macrophages 83:96 The interaction of O-GlcNAc-modified NLRX1 and IKK-α modulates IL-1β expression in M1 macrophages. 35513753 1 34 theme nuclear 187:193 arg1 NF-κB 206:210 NF-κB 206:210 NF-κB 206:210 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 1 34 theme nuclear 187:193 arg1 factor-κB 195:203 nuclear factor-κB 187:203 nuclear factor-κB (NF-κB) signaling 187:221 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 4 35 dep interaction 497:507 arg1 The 493:495 The 493:495 The 493:495 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35513753 6 36 theme O-GlcNAcylation 852:866 arg1 level 868:872 Elevated O-GlcNAcylation level 843:872 Elevated O-GlcNAcylation level 843:872 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 6 37 from expression 1120:1129 arg1 macrophages 1168:1178 M1 macrophages 1165:1178 M1 macrophages 1165:1178 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 3 38 mod modified 438:445 arg3 N-acetylglucosamine 461:479 O-linked N-acetylglucosamine 452:479 O-linked N-acetylglucosamine (O-GlcNAc) 452:490 Here, we found that NLRX1 was modified with O-linked N-acetylglucosamine (O-GlcNAc). 35513753 3 38 mod modified 438:445 arg3 O-GlcNAc 482:489 O-GlcNAc 482:489 O-GlcNAc 482:489 Here, we found that NLRX1 was modified with O-linked N-acetylglucosamine (O-GlcNAc). 35513753 3 38 mod modified 438:445 arg1 NLRX1 428:432 NLRX1 428:432 NLRX1 428:432 Here, we found that NLRX1 was modified with O-linked N-acetylglucosamine (O-GlcNAc). 35513753 0 39 theme IKK-α 47:51 arg1 interaction 4:14 The interaction 0:14 The interaction of O-GlcNAc-modified NLRX1 and IKK-α 0:51 The interaction of O-GlcNAc-modified NLRX1 and IKK-α modulates IL-1β expression in M1 macrophages. 35513753 6 40 theme Elevated 843:850 arg1 level 868:872 Elevated O-GlcNAcylation level 843:872 Elevated O-GlcNAcylation level 843:872 Elevated O-GlcNAcylation level promoted NLRX1 ubiquitination and decreased NLRX1 stability proved by ubiquitination and cycloheximide (CHX) chase experiments, and enhanced the interaction between NLRX1 and inhibitor of nuclear factor kappaB kinase-α (IKK-α), thus reducing the expression of inflammatory cytokine IL-1β in M1 macrophages. 35513753 1 41 theme NLR 118:120 arg1 regulator 147:155 a negative regulator 136:155 a negative regulator of inflammation 136:171 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 1 41 theme NLR 118:120 arg1 NLRX1 126:130 NLRX1 126:130 NLRX1 126:130 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 1 41 theme NLR 118:120 arg1 X1 122:123 NOD-like receptor (NLR)X1 99:123 NOD-like receptor (NLR)X1 (NLRX1) 99:131 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 4 42 with interaction 725:735 arg1 OGT 742:744 OGT 742:744 OGT 742:744 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35513753 1 43 theme NOD-like 99:106 arg1 regulator 147:155 a negative regulator 136:155 a negative regulator of inflammation 136:171 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 1 43 theme NOD-like 99:106 arg1 NLRX1 126:130 NLRX1 126:130 NLRX1 126:130 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 1 43 theme NOD-like 99:106 arg1 X1 122:123 NOD-like receptor (NLR)X1 99:123 NOD-like receptor (NLR)X1 (NLRX1) 99:131 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 1 44 theme factor-κB 195:203 arg1 signaling 213:221 nuclear factor-κB (NF-κB) signaling 187:221 nuclear factor-κB (NF-κB) signaling 187:221 NOD-like receptor (NLR)X1 (NLRX1) is a negative regulator of inflammation by inhibiting nuclear factor-κB (NF-κB) signaling and downstream pro-inflammatory factors. 35513753 2 45 dep modification 296:307 arg1 participates 320:331 participates 320:331 participates in regulating the inflammatory responses in macrophages 320:387 However, its post-translational modification and how it participates in regulating the inflammatory responses in macrophages are still unclear. 35513753 4 46 theme co-immunoprecipitation 591:612 arg1 analysis 638:645 co-immunoprecipitation and confocal microscopy analysis 591:645 co-immunoprecipitation and confocal microscopy analysis 591:645 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35513753 5 47 theme NLRX1 747:751 arg1 protein 753:759 NLRX1 protein 747:759 NLRX1 protein 747:759 NLRX1 protein increased significantly after treatment with a high dose of OGT inhibitor OSMI-1. 35513753 5 48 theme inhibitor 825:833 arg1 OSMI-1 835:840 OGT inhibitor OSMI-1 821:840 OGT inhibitor OSMI-1 821:840 NLRX1 protein increased significantly after treatment with a high dose of OGT inhibitor OSMI-1. 35513753 4 49 theme nucleotide-binding 656:673 arg1 domain 675:680 the nucleotide-binding domain 652:680 the nucleotide-binding domain (NBD) region of NLRX1 652:702 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35513753 4 49 theme nucleotide-binding 656:673 arg1 NBD 683:685 NBD 683:685 NBD 683:685 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35513753 4 50 theme microscopy 627:636 arg1 analysis 638:645 co-immunoprecipitation and confocal microscopy analysis 591:645 co-immunoprecipitation and confocal microscopy analysis 591:645 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35513753 0 51 theme IL-1β 63:67 arg1 expression 69:78 IL-1β expression 63:78 IL-1β expression in M1 macrophages 63:96 The interaction of O-GlcNAc-modified NLRX1 and IKK-α modulates IL-1β expression in M1 macrophages. 35513753 2 52 theme inflammatory 351:362 arg1 responses 364:372 the inflammatory responses 347:372 the inflammatory responses in macrophages 347:387 However, its post-translational modification and how it participates in regulating the inflammatory responses in macrophages are still unclear. 35513753 4 53 theme confocal 618:625 arg1 microscopy 627:636 confocal microscopy 618:636 confocal microscopy 618:636 The interaction and co-localization between NLRX1 and O-GlcNAc transferase (OGT) was validated by co-immunoprecipitation and confocal microscopy analysis, and the nucleotide-binding domain (NBD) region of NLRX1 was required for its interaction with OGT. 35420411 2 0 theme dipolar 366:372 arg1 character 374:382 dipolar character 366:382 dipolar character 366:382 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 1 1 theme vacuum-processed 260:275 arg1 OPD 300:302 OPD 300:302 OPD 300:302 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 1 theme vacuum-processed 260:275 arg1 photodetector 285:297 vacuum-processed organic photodetector 260:297 vacuum-processed organic photodetector (OPD) 260:303 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 3 2 theme superior 547:554 arg1 capability 556:565 the superior capability 543:565 the superior capability of DPSi-DBDTA for dark current suppression 543:608 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 2 3 theme cyclic 324:329 arg1 structure 331:339 The O-Si-O-linked cyclic structure 306:339 The O-Si-O-linked cyclic structure 306:339 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 5 4 theme low 869:871 arg1 density 886:892 low dark current density 869:892 low dark current density 869:892 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 3 5 theme OPD 522:524 arg1 device 526:531 C60-based single active layer OPD device 492:531 C60-based single active layer OPD device 492:531 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 8 6 dep frequency 1349:1357 arg1 kHz 1376:1378 response 692.047 kHz 1359:1378 response 692.047 kHz 1359:1378 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 6 7 with device 973:978 arg1 EBL 999:1001 5% MoO3-doped EBL 985:1001 5% MoO3-doped EBL 985:1001 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 2 8 link O-Si-O-linked 310:322 arg1 structure 331:339 The O-Si-O-linked cyclic structure 306:339 The O-Si-O-linked cyclic structure 306:339 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 3 9 with trial 481:485 arg1 device 526:531 C60-based single active layer OPD device 492:531 C60-based single active layer OPD device 492:531 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 5 10 theme C60-based 850:858 arg1 OPD 860:862 C60-based OPD 850:862 C60-based OPD 850:862 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 9 11 theme Such 1628:1631 arg1 response 1648:1655 Such submicrosecond response 1628:1655 Such submicrosecond response 1628:1655 Such submicrosecond response is comparable with the state-of-the-art perovskite-PDs and Si-PDs. 35420411 6 12 theme carrier 1135:1141 arg1 recombination 1143:1155 carrier recombination 1135:1155 carrier recombination 1135:1155 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 4 13 theme visible 725:731 arg1 OPD 750:752 the visible light responsive OPD 721:752 the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer 721:820 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 5 14 theme specific 903:910 arg1 D 924:924 high specific detectivity D 898:924 high specific detectivity D 898:924 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 8 15 theme transient 1396:1404 arg1 response 1406:1413 record-high transient response 1384:1413 record-high transient response 1384:1413 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 6 16 theme density 1123:1129 arg1 suppression 1090:1100 suppression 1090:1100 suppression of both dark current density and carrier recombination 1090:1155 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 4 17 theme responsive 739:748 arg1 OPD 750:752 the visible light responsive OPD 721:752 the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer 721:820 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 8 18 theme % 1317:1317 arg1 EBL 1330:1332 20% MoO3-doped EBL 1315:1332 20% MoO3-doped EBL 1315:1332 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 5 19 theme D 924:924 arg1 * 925:925 the low dark current density and high specific detectivity D* 865:925 the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) 865:953 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 5 19 theme D 924:924 arg1 W-1 950:952 7.085 × 1012 cm Hz1/2 W-1 928:952 7.085 × 1012 cm Hz1/2 W-1 928:952 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 1 20 theme new 139:141 arg1 layer 244:248 the electron-blocking layer 222:248 the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD) 222:303 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 20 theme new 139:141 arg1 dioxasilepine 143:155 A new dioxasilepine 137:155 A new dioxasilepine 137:155 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 20 theme new 139:141 arg1 DPSi-DBDTA 189:198 aryldiamine hybrid material DPSi-DBDTA 161:198 aryldiamine hybrid material DPSi-DBDTA 161:198 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 6 21 theme dark 1110:1113 arg1 density 1123:1129 dark current density 1110:1129 dark current density 1110:1129 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 0 22 theme Linear 75:80 arg1 Range 90:94 Wide Linear Dynamic Range 70:94 Wide Linear Dynamic Range 70:94 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector. 35420411 5 23 theme current 878:884 arg1 density 886:892 low dark current density 869:892 low dark current density 869:892 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 1 24 theme material 180:187 arg1 DPSi-DBDTA 189:198 aryldiamine hybrid material DPSi-DBDTA 161:198 aryldiamine hybrid material DPSi-DBDTA 161:198 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 24 theme material 180:187 arg1 dioxasilepine 143:155 A new dioxasilepine 137:155 A new dioxasilepine 137:155 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 24 theme material 180:187 arg1 layer 244:248 the electron-blocking layer 222:248 the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD) 222:303 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 8 25 theme transient 1443:1451 arg1 TPV 1467:1469 TPV 1467:1469 TPV 1467:1469 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 8 25 theme transient 1443:1451 arg1 photovoltage 1453:1464 transient photovoltage 1443:1464 transient photovoltage (TPV) 1443:1470 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 4 26 theme DTDCPB/C70 765:774 arg1 layer 816:820 the active layer 805:820 the active layer 805:820 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 4 26 theme DTDCPB/C70 765:774 arg1 BHJ 797:799 BHJ 797:799 BHJ 797:799 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 4 26 theme DTDCPB/C70 765:774 arg1 heterojunction 781:794 DTDCPB/C70 bulk heterojunction 765:794 DTDCPB/C70 bulk heterojunction (BHJ) 765:800 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 0 27 theme Fast 100:103 arg1 Photodetector 122:134 Fast Response Organic Photodetector 100:134 Fast Response Organic Photodetector 100:134 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector. 35420411 5 28 theme cm 941:942 arg1 * 925:925 the low dark current density and high specific detectivity D* 865:925 the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) 865:953 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 5 28 theme cm 941:942 arg1 W-1 950:952 7.085 × 1012 cm Hz1/2 W-1 928:952 7.085 × 1012 cm Hz1/2 W-1 928:952 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 0 29 theme Organic 114:120 arg1 Photodetector 122:134 Fast Response Organic Photodetector 100:134 Fast Response Organic Photodetector 100:134 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector. 35420411 6 30 theme wide 1017:1020 arg1 LDR 1044:1046 LDR 1044:1046 LDR 1044:1046 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 6 30 theme wide 1017:1020 arg1 range 1037:1041 a wide linear dynamic range 1015:1041 a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination 1015:1155 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 7 31 theme transient 1251:1259 arg1 measurements 1270:1281 transient response measurements 1251:1281 transient response measurements 1251:1281 Additionally, the devices also manifest fast time-resolved performance in both frequency and transient response measurements. 35420411 9 32 with comparable 1660:1669 arg1 Si-PDs 1716:1721 Si-PDs 1716:1721 Si-PDs 1716:1721 Such submicrosecond response is comparable with the state-of-the-art perovskite-PDs and Si-PDs. 35420411 9 32 with comparable 1660:1669 arg1 perovskite-PDs 1697:1710 the state-of-the-art perovskite-PDs 1676:1710 the state-of-the-art perovskite-PDs 1676:1710 Such submicrosecond response is comparable with the state-of-the-art perovskite-PDs and Si-PDs. 35420411 8 33 dep EBL 1330:1332 arg1 the 1299:1301 the 1299:1301 the 1299:1301 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 8 33 dep EBL 1330:1332 arg1 device 1303:1308 device 1303:1308 device 1303:1308 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 4 34 theme bulk 776:779 arg1 layer 816:820 the active layer 805:820 the active layer 805:820 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 4 34 theme bulk 776:779 arg1 BHJ 797:799 BHJ 797:799 BHJ 797:799 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 4 34 theme bulk 776:779 arg1 heterojunction 781:794 DTDCPB/C70 bulk heterojunction 765:794 DTDCPB/C70 bulk heterojunction (BHJ) 765:800 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 3 35 theme initial 473:479 arg1 trial 481:485 An initial trial 470:485 An initial trial with C60-based single active layer OPD device 470:531 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 0 36 theme Dioxasilepine-Aryldiamine 6:30 arg1 Material 57:64 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material 0:64 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector 0:134 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector. 35420411 5 37 theme × 934:934 arg1 * 925:925 the low dark current density and high specific detectivity D* 865:925 the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) 865:953 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 5 37 theme × 934:934 arg1 W-1 950:952 7.085 × 1012 cm Hz1/2 W-1 928:952 7.085 × 1012 cm Hz1/2 W-1 928:952 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 0 38 theme Electron-Blocking 39:55 arg1 Material 57:64 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material 0:64 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector 0:134 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector. 35420411 7 39 from performance 1217:1227 arg1 frequency 1237:1245 frequency 1237:1245 frequency 1237:1245 Additionally, the devices also manifest fast time-resolved performance in both frequency and transient response measurements. 35420411 7 39 from performance 1217:1227 arg1 measurements 1270:1281 transient response measurements 1251:1281 transient response measurements 1251:1281 Additionally, the devices also manifest fast time-resolved performance in both frequency and transient response measurements. 35420411 6 40 theme % 986:986 arg1 EBL 999:1001 5% MoO3-doped EBL 985:1001 5% MoO3-doped EBL 985:1001 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 3 41 theme single 502:507 arg1 device 526:531 C60-based single active layer OPD device 492:531 C60-based single active layer OPD device 492:531 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 7 42 theme time-resolved 1203:1215 arg1 performance 1217:1227 fast time-resolved performance 1198:1227 fast time-resolved performance in both frequency and transient response measurements 1198:1281 Additionally, the devices also manifest fast time-resolved performance in both frequency and transient response measurements. 35420411 8 43 theme cutoff 1342:1347 arg1 frequency 1349:1357 a wide cutoff frequency response 692.047 kHz and record-high transient response 1335:1413 frequency 1349:1357 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 8 44 from traps 1621:1625 arg1 damage 1609:1614 the damage 1605:1614 the damage from traps 1605:1625 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 1 45 theme aryldiamine 161:171 arg1 DPSi-DBDTA 189:198 aryldiamine hybrid material DPSi-DBDTA 161:198 aryldiamine hybrid material DPSi-DBDTA 161:198 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 45 theme aryldiamine 161:171 arg1 dioxasilepine 143:155 A new dioxasilepine 137:155 A new dioxasilepine 137:155 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 45 theme aryldiamine 161:171 arg1 layer 244:248 the electron-blocking layer 222:248 the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD) 222:303 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 8 46 theme response 1359:1366 arg1 kHz 1376:1378 response 692.047 kHz 1359:1378 response 692.047 kHz 1359:1378 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 2 47 theme high 385:388 arg1 LUMO 390:393 high LUMO 385:393 high LUMO 385:393 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 4 48 theme MoO3-doped 667:676 arg1 EBLs 712:715 EBLs 712:715 EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer 712:820 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 4 48 theme MoO3-doped 667:676 arg1 DPSi-DBDTA 678:687 the bare and MoO3-doped DPSi-DBDTA 654:687 the bare and MoO3-doped DPSi-DBDTA 654:687 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 3 49 theme layer 516:520 arg1 device 526:531 C60-based single active layer OPD device 492:531 C60-based single active layer OPD device 492:531 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 8 50 theme mobility 1581:1588 arg1 balance 1570:1576 the balance 1566:1576 the balance of mobility that mitigates the damage from traps 1566:1625 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 6 51 theme dynamic 1029:1035 arg1 LDR 1044:1046 LDR 1044:1046 LDR 1044:1046 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 6 51 theme dynamic 1029:1035 arg1 range 1037:1041 a wide linear dynamic range 1015:1041 a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination 1015:1155 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 1 52 theme organic 277:283 arg1 OPD 300:302 OPD 300:302 OPD 300:302 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 52 theme organic 277:283 arg1 photodetector 285:297 vacuum-processed organic photodetector 260:297 vacuum-processed organic photodetector (OPD) 260:303 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 5 53 theme density 886:892 arg1 * 925:925 the low dark current density and high specific detectivity D* 865:925 the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) 865:953 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 5 53 theme density 886:892 arg1 W-1 950:952 7.085 × 1012 cm Hz1/2 W-1 928:952 7.085 × 1012 cm Hz1/2 W-1 928:952 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 5 54 theme OPD 860:862 arg1 result 840:845 the result 836:845 the result of C60-based OPD 836:862 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 6 55 dep dB 1063:1064 arg1 up 1049:1050 up 1049:1050 up 1049:1050 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 3 56 theme dark 585:588 arg1 suppression 598:608 dark current suppression 585:608 dark current suppression 585:608 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 2 57 theme O-Si-O-linked 310:322 arg1 structure 331:339 The O-Si-O-linked cyclic structure 306:339 The O-Si-O-linked cyclic structure 306:339 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 3 58 theme current 590:596 arg1 suppression 598:608 dark current suppression 585:608 dark current suppression 585:608 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 8 59 theme record-high 1384:1394 arg1 response 1406:1413 record-high transient response 1384:1413 record-high transient response 1384:1413 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 6 60 theme recombination 1143:1155 arg1 suppression 1090:1100 suppression 1090:1100 suppression of both dark current density and carrier recombination 1090:1155 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 4 61 theme bare 658:661 arg1 EBLs 712:715 EBLs 712:715 EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer 712:820 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 4 61 theme bare 658:661 arg1 DPSi-DBDTA 678:687 the bare and MoO3-doped DPSi-DBDTA 654:687 the bare and MoO3-doped DPSi-DBDTA 654:687 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 5 62 theme high 898:901 arg1 D 924:924 high specific detectivity D 898:924 high specific detectivity D 898:924 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 9 63 theme submicrosecond 1633:1646 arg1 response 1648:1655 Such submicrosecond response 1628:1655 Such submicrosecond response 1628:1655 Such submicrosecond response is comparable with the state-of-the-art perovskite-PDs and Si-PDs. 35420411 5 64 theme detectivity 912:922 arg1 D 924:924 high specific detectivity D 898:924 high specific detectivity D 898:924 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 3 65 theme DPSi-DBDTA 570:579 arg1 capability 556:565 the superior capability 543:565 the superior capability of DPSi-DBDTA for dark current suppression 543:608 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 6 66 theme 5 985:985 arg1 % 986:986 % 986:986 % 986:986 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 6 67 theme current 1115:1121 arg1 density 1123:1129 dark current density 1110:1129 dark current density 1110:1129 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 4 68 theme light 733:737 arg1 OPD 750:752 the visible light responsive OPD 721:752 the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer 721:820 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 0 69 theme Dynamic 82:88 arg1 Range 90:94 Wide Linear Dynamic Range 70:94 Wide Linear Dynamic Range 70:94 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector. 35420411 3 70 theme typical 626:632 arg1 aryldiamines 634:645 the typical aryldiamines 622:645 the typical aryldiamines 622:645 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 5 71 theme dark 873:876 arg1 density 886:892 low dark current density 869:892 low dark current density 869:892 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 1 72 theme hybrid 173:178 arg1 DPSi-DBDTA 189:198 aryldiamine hybrid material DPSi-DBDTA 161:198 aryldiamine hybrid material DPSi-DBDTA 161:198 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 72 theme hybrid 173:178 arg1 dioxasilepine 143:155 A new dioxasilepine 137:155 A new dioxasilepine 137:155 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 72 theme hybrid 173:178 arg1 layer 244:248 the electron-blocking layer 222:248 the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD) 222:303 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 9 73 theme state-of-the-art 1680:1695 arg1 perovskite-PDs 1697:1710 the state-of-the-art perovskite-PDs 1676:1710 the state-of-the-art perovskite-PDs 1676:1710 Such submicrosecond response is comparable with the state-of-the-art perovskite-PDs and Si-PDs. 35420411 0 74 theme Response 105:112 arg1 Photodetector 122:134 Fast Response Organic Photodetector 100:134 Fast Response Organic Photodetector 100:134 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector. 35420411 2 75 contain have 361:364 arg2 LUMO 390:393 high LUMO 385:393 high LUMO 385:393 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 2 75 contain have 361:364 arg2 character 374:382 dipolar character 366:382 dipolar character 366:382 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 2 75 contain have 361:364 arg1 DPSi-DBDTA 347:356 DPSi-DBDTA 347:356 DPSi-DBDTA 347:356 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 2 75 contain have 361:364 arg2 thermal 405:411 thermal 405:411 thermal 405:411 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 5 76 theme Hz1/2 944:948 arg1 * 925:925 the low dark current density and high specific detectivity D* 865:925 the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) 865:953 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 5 76 theme Hz1/2 944:948 arg1 W-1 950:952 7.085 × 1012 cm Hz1/2 W-1 928:952 7.085 × 1012 cm Hz1/2 W-1 928:952 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 35420411 6 77 theme linear 1022:1027 arg1 LDR 1044:1046 LDR 1044:1046 LDR 1044:1046 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 6 77 theme linear 1022:1027 arg1 range 1037:1041 a wide linear dynamic range 1015:1041 a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination 1015:1155 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 0 78 theme New 2:4 arg1 Material 57:64 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material 0:64 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector 0:134 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector. 35420411 2 79 theme vacuum 451:456 arg1 deposition 458:467 vacuum deposition 451:467 vacuum deposition 451:467 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 0 80 theme Hybrid 32:37 arg1 Material 57:64 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material 0:64 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector 0:134 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector. 35420411 8 81 theme transient 1490:1498 arg1 TPC 1514:1516 TPC 1514:1516 TPC 1514:1516 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 8 81 theme transient 1490:1498 arg1 photocurrent 1500:1511 transient photocurrent 1490:1511 transient photocurrent (TPC) 1490:1517 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 8 82 theme 20 1315:1316 arg1 % 1317:1317 % 1317:1317 % 1317:1317 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 2 83 theme morphology 417:426 arg1 stability 428:436 good thermal and morphology stability 400:436 stability 428:436 The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. 35420411 6 84 theme MoO3-doped 988:997 arg1 EBL 999:1001 5% MoO3-doped EBL 985:1001 5% MoO3-doped EBL 985:1001 The device with 5% MoO3-doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. 35420411 7 85 theme response 1261:1268 arg1 measurements 1270:1281 transient response measurements 1251:1281 transient response measurements 1251:1281 Additionally, the devices also manifest fast time-resolved performance in both frequency and transient response measurements. 35420411 8 86 theme MoO3-doped 1319:1328 arg1 EBL 1330:1332 20% MoO3-doped EBL 1315:1332 20% MoO3-doped EBL 1315:1332 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 0 87 theme Wide 70:73 arg1 Range 90:94 Wide Linear Dynamic Range 70:94 Wide Linear Dynamic Range 70:94 A New Dioxasilepine-Aryldiamine Hybrid Electron-Blocking Material for Wide Linear Dynamic Range and Fast Response Organic Photodetector. 35420411 7 88 theme fast 1198:1201 arg1 performance 1217:1227 fast time-resolved performance 1198:1227 fast time-resolved performance in both frequency and transient response measurements 1198:1281 Additionally, the devices also manifest fast time-resolved performance in both frequency and transient response measurements. 35420411 3 89 theme active 509:514 arg1 device 526:531 C60-based single active layer OPD device 492:531 C60-based single active layer OPD device 492:531 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 4 90 theme active 809:814 arg1 layer 816:820 the active layer 805:820 the active layer 805:820 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 4 90 theme active 809:814 arg1 heterojunction 781:794 DTDCPB/C70 bulk heterojunction 765:794 DTDCPB/C70 bulk heterojunction (BHJ) 765:800 Here, the bare and MoO3-doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB/C70 bulk heterojunction (BHJ) as the active layer. 35420411 8 91 theme wide 1337:1340 arg1 frequency 1349:1357 a wide cutoff frequency response 692.047 kHz and record-high transient response 1335:1413 frequency 1349:1357 Especially for the device with 20% MoO3-doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. 35420411 3 92 theme C60-based 492:500 arg1 device 526:531 C60-based single active layer OPD device 492:531 C60-based single active layer OPD device 492:531 An initial trial with C60-based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. 35420411 1 93 theme electron-blocking 226:242 arg1 EBL 251:253 EBL 251:253 EBL 251:253 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 93 theme electron-blocking 226:242 arg1 layer 244:248 the electron-blocking layer 222:248 the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD) 222:303 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 93 theme electron-blocking 226:242 arg1 dioxasilepine 143:155 A new dioxasilepine 137:155 A new dioxasilepine 137:155 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 1 93 theme electron-blocking 226:242 arg1 DPSi-DBDTA 189:198 aryldiamine hybrid material DPSi-DBDTA 161:198 aryldiamine hybrid material DPSi-DBDTA 161:198 A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). 35420411 5 94 dep result 840:845 arg1 sync 826:829 sync 826:829 sync 826:829 In sync with the result of C60-based OPD, the low dark current density and high specific detectivity D* (7.085 × 1012 cm Hz1/2 W-1) are achieved. 36285383 3 0 link azine-linked 576:587 arg1 imine-linked 562:573 imine-linked 562:573 imine-linked 562:573 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 1 1 theme crystalline 149:159 arg1 polymers 161:168 porous crystalline polymers 142:168 porous crystalline polymers with well-defined structures and tunable functionalities 142:225 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 4 2 theme traditional 816:826 arg1 routes 841:846 traditional solvothermal routes 816:846 traditional solvothermal routes 816:846 The crystallinity and porosity of these COFs are comparable to those prepared by traditional solvothermal routes. 36285383 3 3 theme methods 713:719 arg1 disadvantages 683:695 the disadvantages 679:695 the disadvantages of solvothermal methods 679:719 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 1 4 with polymers 161:168 arg1 structures 188:197 well-defined structures 175:197 well-defined structures 175:197 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 4 with polymers 161:168 arg1 functionalities 211:225 tunable functionalities 203:225 tunable functionalities 203:225 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 5 theme polymers 161:168 arg1 class 133:137 an emerging class 121:137 an emerging class 121:137 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 5 theme polymers 161:168 arg1 frameworks 99:108 Covalent organic frameworks 82:108 Covalent organic frameworks (COFs) 82:115 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 6 theme wide 269:272 arg1 range 274:278 a wide range 267:278 a wide range of fields 267:288 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 3 7 theme two-dimensional 526:540 arg1 COFs 547:550 two-dimensional (2D) COFs 526:550 two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods 526:719 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 3 7 theme two-dimensional 526:540 arg1 imine-linked 562:573 imine-linked 562:573 imine-linked 562:573 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 3 8 theme COFs 547:550 arg1 series 516:521 a series 514:521 a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods 514:719 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 3 9 dep azine-linked 576:587 arg1 β-ketoenamine-linked 590:609 β-ketoenamine-linked 590:609 β-ketoenamine-linked 590:609 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 5 10 theme COFs 952:955 arg1 gram-scale 929:938 gram-scale 929:938 gram-scale of those 2D COFs 929:955 What's more, the advantages of the solvent-free method enable the production of gram-scale of those 2D COFs through a one-pot reaction, demonstrating high industrial application potentials. 36285383 1 11 theme Covalent 82:89 arg1 class 133:137 an emerging class 121:137 an emerging class 121:137 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 11 theme Covalent 82:89 arg1 COFs 111:114 COFs 111:114 COFs 111:114 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 11 theme Covalent 82:89 arg1 frameworks 99:108 Covalent organic frameworks 82:108 Covalent organic frameworks (COFs) 82:115 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 5 12 theme 2D 949:950 arg1 COFs 952:955 those 2D COFs 943:955 those 2D COFs 943:955 What's more, the advantages of the solvent-free method enable the production of gram-scale of those 2D COFs through a one-pot reaction, demonstrating high industrial application potentials. 36285383 5 13 theme gram-scale 929:938 arg1 production 915:924 the production 911:924 the production of gram-scale of those 2D COFs 911:955 What's more, the advantages of the solvent-free method enable the production of gram-scale of those 2D COFs through a one-pot reaction, demonstrating high industrial application potentials. 36285383 1 14 theme organic 91:97 arg1 class 133:137 an emerging class 121:137 an emerging class 121:137 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 14 theme organic 91:97 arg1 COFs 111:114 COFs 111:114 COFs 111:114 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 14 theme organic 91:97 arg1 frameworks 99:108 Covalent organic frameworks 82:108 Covalent organic frameworks (COFs) 82:115 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 15 theme well-defined 175:186 arg1 structures 188:197 well-defined structures 175:197 well-defined structures 175:197 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 5 16 theme one-pot 967:973 arg1 reaction 975:982 a one-pot reaction 965:982 a one-pot reaction 965:982 What's more, the advantages of the solvent-free method enable the production of gram-scale of those 2D COFs through a one-pot reaction, demonstrating high industrial application potentials. 36285383 5 17 theme method 897:902 arg1 advantages 866:875 the advantages 862:875 the advantages of the solvent-free method 862:902 What's more, the advantages of the solvent-free method enable the production of gram-scale of those 2D COFs through a one-pot reaction, demonstrating high industrial application potentials. 36285383 0 18 theme Solvent-Free 0:11 arg1 Synthesis 13:21 Solvent-Free Synthesis 0:21 Solvent-Free Synthesis of C=N 0:28 Solvent-Free Synthesis of C=N Linked Two-Dimensional Covalent Organic Frameworks. 36285383 1 19 theme fields 283:288 arg1 range 274:278 a wide range 267:278 a wide range of fields 267:288 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 0 20 theme C=N 26:28 arg1 Synthesis 13:21 Solvent-Free Synthesis 0:21 Solvent-Free Synthesis of C=N 0:28 Solvent-Free Synthesis of C=N Linked Two-Dimensional Covalent Organic Frameworks. 36285383 1 21 contain have 234:237 arg1 class 133:137 an emerging class 121:137 an emerging class 121:137 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 21 contain have 234:237 arg1 frameworks 99:108 Covalent organic frameworks 82:108 Covalent organic frameworks (COFs) 82:115 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 21 contain have 234:237 arg2 applications 251:262 fascinating applications 239:262 fascinating applications 239:262 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 2 22 theme synthetic 304:312 arg1 procedures 314:323 the synthetic procedures 300:323 the synthetic procedures of COFs 300:331 However, the synthetic procedures of COFs are mainly confined to the solvothermal synthesis method which usually requires harsh experimental conditions. 36285383 1 23 theme tunable 203:209 arg1 functionalities 211:225 tunable functionalities 203:225 tunable functionalities 203:225 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 5 24 theme high 999:1002 arg1 application 1015:1025 high industrial application 999:1025 high industrial application potentials 999:1036 What's more, the advantages of the solvent-free method enable the production of gram-scale of those 2D COFs through a one-pot reaction, demonstrating high industrial application potentials. 36285383 4 25 theme COFs 775:778 arg1 crystallinity 739:751 crystallinity 739:751 crystallinity 739:751 The crystallinity and porosity of these COFs are comparable to those prepared by traditional solvothermal routes. 36285383 4 25 theme COFs 775:778 arg1 comparable 784:793 comparable 784:793 comparable 784:793 The crystallinity and porosity of these COFs are comparable to those prepared by traditional solvothermal routes. 36285383 4 25 theme COFs 775:778 arg1 porosity 757:764 porosity 757:764 porosity 757:764 The crystallinity and porosity of these COFs are comparable to those prepared by traditional solvothermal routes. 36285383 3 26 theme synthesis 484:492 arg1 method 494:499 an effective solvent-free synthesis method 458:499 an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods 458:719 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 0 27 theme Two-Dimensional 37:51 arg1 Frameworks 70:79 Two-Dimensional Covalent Organic Frameworks 37:79 Two-Dimensional Covalent Organic Frameworks 37:79 Solvent-Free Synthesis of C=N Linked Two-Dimensional Covalent Organic Frameworks. 36285383 2 28 theme experimental 419:430 arg1 conditions 432:441 harsh experimental conditions 413:441 harsh experimental conditions 413:441 However, the synthetic procedures of COFs are mainly confined to the solvothermal synthesis method which usually requires harsh experimental conditions. 36285383 2 29 theme harsh 413:417 arg1 conditions 432:441 harsh experimental conditions 413:441 harsh experimental conditions 413:441 However, the synthetic procedures of COFs are mainly confined to the solvothermal synthesis method which usually requires harsh experimental conditions. 36285383 0 30 theme Organic 62:68 arg1 Frameworks 70:79 Two-Dimensional Covalent Organic Frameworks 37:79 Two-Dimensional Covalent Organic Frameworks 37:79 Solvent-Free Synthesis of C=N Linked Two-Dimensional Covalent Organic Frameworks. 36285383 0 31 theme Covalent 53:60 arg1 Frameworks 70:79 Two-Dimensional Covalent Organic Frameworks 37:79 Two-Dimensional Covalent Organic Frameworks 37:79 Solvent-Free Synthesis of C=N Linked Two-Dimensional Covalent Organic Frameworks. 36285383 3 32 dep method 494:499 arg1 construct 504:512 construct 504:512 to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods 501:719 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 1 33 theme porous 142:147 arg1 polymers 161:168 porous crystalline polymers 142:168 porous crystalline polymers with well-defined structures and tunable functionalities 142:225 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 4 34 theme solvothermal 828:839 arg1 routes 841:846 traditional solvothermal routes 816:846 traditional solvothermal routes 816:846 The crystallinity and porosity of these COFs are comparable to those prepared by traditional solvothermal routes. 36285383 3 35 theme solvothermal 700:711 arg1 methods 713:719 solvothermal methods 700:719 solvothermal methods 700:719 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 3 36 theme solvent 641:647 arg1 process 659:665 the complicated solvent screening process 625:665 the complicated solvent screening process 625:665 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 1 37 theme emerging 124:131 arg1 class 133:137 an emerging class 121:137 an emerging class 121:137 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 1 37 theme emerging 124:131 arg1 frameworks 99:108 Covalent organic frameworks 82:108 Covalent organic frameworks (COFs) 82:115 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 3 38 dep two-dimensional 526:540 arg1 2D 543:544 2D 543:544 2D 543:544 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 5 39 theme industrial 1004:1013 arg1 application 1015:1025 high industrial application 999:1025 high industrial application potentials 999:1036 What's more, the advantages of the solvent-free method enable the production of gram-scale of those 2D COFs through a one-pot reaction, demonstrating high industrial application potentials. 36285383 3 40 theme screening 649:657 arg1 process 659:665 the complicated solvent screening process 625:665 the complicated solvent screening process 625:665 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 2 41 theme COFs 328:331 arg1 procedures 314:323 the synthetic procedures 300:323 the synthetic procedures of COFs 300:331 However, the synthetic procedures of COFs are mainly confined to the solvothermal synthesis method which usually requires harsh experimental conditions. 36285383 1 42 theme fascinating 239:249 arg1 applications 251:262 fascinating applications 239:262 fascinating applications 239:262 Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers with well-defined structures and tunable functionalities, which have fascinating applications in a wide range of fields. 36285383 3 43 theme effective 461:469 arg1 method 494:499 an effective solvent-free synthesis method 458:499 an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods 458:719 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 3 44 theme solvent-free 471:482 arg1 method 494:499 an effective solvent-free synthesis method 458:499 an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods 458:719 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 2 45 theme synthesis 373:381 arg1 method 383:388 the solvothermal synthesis method 356:388 the solvothermal synthesis method which usually requires harsh experimental conditions 356:441 However, the synthetic procedures of COFs are mainly confined to the solvothermal synthesis method which usually requires harsh experimental conditions. 36285383 5 46 theme solvent-free 884:895 arg1 method 897:902 the solvent-free method 880:902 the solvent-free method 880:902 What's more, the advantages of the solvent-free method enable the production of gram-scale of those 2D COFs through a one-pot reaction, demonstrating high industrial application potentials. 36285383 5 47 theme application 1015:1025 arg1 potentials 1027:1036 high industrial application potentials 999:1036 high industrial application potentials 999:1036 What's more, the advantages of the solvent-free method enable the production of gram-scale of those 2D COFs through a one-pot reaction, demonstrating high industrial application potentials. 36285383 3 48 theme complicated 629:639 arg1 process 659:665 the complicated solvent screening process 625:665 the complicated solvent screening process 625:665 In this work, an effective solvent-free synthesis method to construct a series of two-dimensional (2D) COFs including imine-linked, azine-linked, β-ketoenamine-linked, which avoids the complicated solvent screening process and most of the disadvantages of solvothermal methods is developed. 36285383 2 49 theme solvothermal 360:371 arg1 method 383:388 the solvothermal synthesis method 356:388 the solvothermal synthesis method which usually requires harsh experimental conditions 356:441 However, the synthetic procedures of COFs are mainly confined to the solvothermal synthesis method which usually requires harsh experimental conditions. 35820058 3 0 theme profiles 713:720 arg1 separation 770:779 separation 770:779 separation 770:779 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 3 0 theme profiles 713:720 arg1 detection 785:793 detection 785:793 detection 785:793 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 3 0 theme profiles 713:720 arg1 incubation 723:732 incubation 723:732 incubation in a thermostatic zone 723:755 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 3 0 theme profiles 713:720 arg1 diffusion 687:695 transverse diffusion 676:695 transverse diffusion of laminar flow profiles 676:720 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 6 1 theme full 1321:1324 arg1 automation 1326:1335 full automation 1321:1335 full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis 1321:1437 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 1 2 theme in-capillary 138:149 arg1 labeling 163:170 in-capillary fluorescent labeling 138:170 in-capillary fluorescent labeling of N-glycans 138:183 In this study, we present a new approach for in-capillary fluorescent labeling of N-glycans prior to their analysis with CE coupled with laser-induced fluorescent detection. 35820058 1 3 theme fluorescent 244:254 arg1 detection 256:264 laser-induced fluorescent detection 230:264 laser-induced fluorescent detection 230:264 In this study, we present a new approach for in-capillary fluorescent labeling of N-glycans prior to their analysis with CE coupled with laser-induced fluorescent detection. 35820058 3 4 from diffusion 687:695 arg1 zone 752:755 a thermostatic zone 737:755 a thermostatic zone 737:755 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 3 5 from separation 770:779 arg1 zone 752:755 a thermostatic zone 737:755 a thermostatic zone 737:755 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 4 6 from feasible 873:880 arg1 mode 909:912 batchwise mode 899:912 batchwise mode 899:912 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode can now be converted into an automated and integrated protocol. 35820058 1 7 theme fluorescent 151:161 arg1 labeling 163:170 in-capillary fluorescent labeling 138:170 in-capillary fluorescent labeling of N-glycans 138:183 In this study, we present a new approach for in-capillary fluorescent labeling of N-glycans prior to their analysis with CE coupled with laser-induced fluorescent detection. 35820058 6 8 theme capillary 1413:1421 arg1 electrophoresis 1423:1437 capillary electrophoresis 1413:1437 capillary electrophoresis 1413:1437 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 3 9 theme laminar 700:706 arg1 profiles 713:720 laminar flow profiles 700:720 laminar flow profiles 700:720 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 4 10 theme treatment 826:834 arg1 protocol 836:843 Such a complex sample treatment protocol 804:843 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode 804:912 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode can now be converted into an automated and integrated protocol. 35820058 3 11 from detection 785:793 arg1 zone 752:755 a thermostatic zone 737:755 a thermostatic zone 737:755 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 6 12 theme reagent 1297:1303 arg1 consumption 1305:1315 fourfold less reagent consumption 1283:1315 fourfold less reagent consumption 1283:1315 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 3 13 theme careful 552:558 arg1 optimization 560:571 careful optimization 552:571 careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs 552:663 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 6 14 theme separation 1382:1391 arg1 profile 1393:1399 the glycan separation profile 1371:1399 the glycan separation profile obtained by capillary electrophoresis 1371:1437 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 4 15 theme automated 943:951 arg1 protocol 968:975 an automated and integrated protocol 940:975 an automated and integrated protocol 940:975 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode can now be converted into an automated and integrated protocol. 35820058 6 16 theme less 1292:1295 arg1 consumption 1305:1315 fourfold less reagent consumption 1283:1315 fourfold less reagent consumption 1283:1315 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 0 17 gly glycoproteins 78:90 arg1 glycoproteins 78:90 glycoproteins 78:90 glycoproteins 78:90 In capillary labeling and online electrophoretic separation of N-glycans from glycoproteins. 35820058 2 18 theme 8-aminopyrene-1,3,6 398:416 arg1 acid 430:433 8-aminopyrene-1,3,6 trisulfonic acid 398:433 8-aminopyrene-1,3,6 trisulfonic acid 398:433 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 2 19 theme glycans 512:518 arg1 CE 484:485 CE 484:485 CE of fluorescently labeled glycans 484:518 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 5 20 theme monoclonal 1129:1138 arg1 antibody 1140:1147 a monoclonal antibody 1127:1147 a monoclonal antibody used for cancer treatment 1127:1173 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 5 20 theme monoclonal 1129:1138 arg1 rituximab 1116:1124 rituximab 1116:1124 rituximab 1116:1124 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 2 21 theme integrated 272:281 arg1 approach 283:290 This integrated approach 267:290 This integrated approach 267:290 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 0 22 theme capillary 3:11 arg1 labeling 13:20 capillary labeling 3:20 capillary labeling 3:20 In capillary labeling and online electrophoretic separation of N-glycans from glycoproteins. 35820058 4 23 theme integrated 957:966 arg1 protocol 968:975 an automated and integrated protocol 940:975 an automated and integrated protocol 940:975 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode can now be converted into an automated and integrated protocol. 35820058 6 24 theme remarkable 1345:1354 arg1 degradation 1356:1366 remarkable degradation 1345:1366 remarkable degradation of the glycan separation profile obtained by capillary electrophoresis 1345:1437 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 1 25 theme N-glycans 175:183 arg1 labeling 163:170 in-capillary fluorescent labeling 138:170 in-capillary fluorescent labeling of N-glycans 138:183 In this study, we present a new approach for in-capillary fluorescent labeling of N-glycans prior to their analysis with CE coupled with laser-induced fluorescent detection. 35820058 3 26 from incubation 723:732 arg1 zone 752:755 a thermostatic zone 737:755 a thermostatic zone 737:755 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 4 27 theme glycan 849:854 arg1 labeling 856:863 glycan labeling 849:863 glycan labeling that is feasible thus far only in batchwise mode 849:912 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode can now be converted into an automated and integrated protocol. 35820058 3 28 theme different 580:588 arg1 steps 590:594 all different steps 576:594 all different steps 576:594 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 3 28 theme different 580:588 arg1 injections 618:627 sequential injections 607:627 sequential injections of fluorescent dye and glycan plugs 607:663 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 5 29 theme human 1089:1093 arg1 G 1110:1110 human immunoglobulin G 1089:1110 human immunoglobulin G 1089:1110 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 2 30 theme same 446:449 arg1 time 451:454 the same time 442:454 the same time 442:454 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 1 31 with analysis 200:207 arg1 CE 214:215 CE 214:215 CE coupled with laser-induced fluorescent detection 214:264 In this study, we present a new approach for in-capillary fluorescent labeling of N-glycans prior to their analysis with CE coupled with laser-induced fluorescent detection. 35820058 6 32 theme profile 1393:1399 arg1 degradation 1356:1366 remarkable degradation 1345:1366 remarkable degradation of the glycan separation profile obtained by capillary electrophoresis 1345:1437 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 2 33 theme CE 307:308 arg1 capillary 310:318 a CE capillary 305:318 a CE capillary 305:318 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 2 33 theme CE 307:308 arg1 microreactor 325:336 a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans 323:518 a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans 323:518 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 5 34 theme labeled 1041:1047 arg1 oligosaccharides 1058:1073 fluorescently labeled N-linked oligosaccharides 1027:1073 fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment 1027:1173 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 3 35 theme thermostatic 739:750 arg1 zone 752:755 a thermostatic zone 737:755 a thermostatic zone 737:755 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 6 36 theme glycan 1375:1380 arg1 profile 1393:1399 the glycan separation profile 1371:1399 the glycan separation profile obtained by capillary electrophoresis 1371:1437 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 3 37 theme plugs 659:663 arg1 injections 618:627 sequential injections 607:627 sequential injections of fluorescent dye and glycan plugs 607:663 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 2 38 theme several 349:355 arg1 steps 357:361 several steps 349:361 several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans 349:518 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 0 39 theme electrophoretic 33:47 arg1 separation 49:58 online electrophoretic separation 26:58 online electrophoretic separation of N-glycans from glycoproteins 26:90 In capillary labeling and online electrophoretic separation of N-glycans from glycoproteins. 35820058 6 40 theme conventional 1247:1258 arg1 protocol 1268:1275 the conventional in-tube protocol 1243:1275 the conventional in-tube protocol 1243:1275 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 0 41 from glycoproteins 78:90 arg1 labeling 13:20 capillary labeling 3:20 capillary labeling 3:20 In capillary labeling and online electrophoretic separation of N-glycans from glycoproteins. 35820058 0 41 from glycoproteins 78:90 arg1 separation 49:58 online electrophoretic separation 26:58 online electrophoretic separation of N-glycans from glycoproteins 26:90 In capillary labeling and online electrophoretic separation of N-glycans from glycoproteins. 35820058 4 42 theme complex 811:817 arg1 protocol 836:843 Such a complex sample treatment protocol 804:843 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode 804:912 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode can now be converted into an automated and integrated protocol. 35820058 5 43 attach released 1075:1082 arg1 antibody 1140:1147 a monoclonal antibody 1127:1147 a monoclonal antibody used for cancer treatment 1127:1173 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 5 43 attach released 1075:1082 arg1 G 1110:1110 human immunoglobulin G 1089:1110 human immunoglobulin G 1089:1110 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 5 43 attach released 1075:1082 arg1 rituximab 1116:1124 rituximab 1116:1124 rituximab 1116:1124 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 5 43 attach released 1075:1082 arg2 oligosaccharides 1058:1073 fluorescently labeled N-linked oligosaccharides 1027:1073 fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment 1027:1173 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 0 44 theme online 26:31 arg1 separation 49:58 online electrophoretic separation 26:58 online electrophoretic separation of N-glycans from glycoproteins 26:90 In capillary labeling and online electrophoretic separation of N-glycans from glycoproteins. 35820058 5 45 theme cancer 1158:1163 arg1 treatment 1165:1173 cancer treatment 1158:1173 cancer treatment 1158:1173 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 5 46 theme immunoglobulin 1095:1108 arg1 G 1110:1110 human immunoglobulin G 1089:1110 human immunoglobulin G 1089:1110 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 3 47 theme sequential 607:616 arg1 injections 618:627 sequential injections 607:627 sequential injections of fluorescent dye and glycan plugs 607:663 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 2 48 theme trisulfonic 418:428 arg1 acid 430:433 8-aminopyrene-1,3,6 trisulfonic acid 398:433 8-aminopyrene-1,3,6 trisulfonic acid 398:433 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 2 49 theme separation 461:470 arg1 channel 472:478 a separation channel 459:478 a separation channel for CE of fluorescently labeled glycans 459:518 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 2 49 theme separation 461:470 arg1 glycans 385:391 glycans 385:391 glycans 385:391 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 3 50 theme glycan 652:657 arg1 plugs 659:663 glycan plugs 652:663 glycan plugs 652:663 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 3 51 theme steps 590:594 arg1 optimization 560:571 careful optimization 552:571 careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs 552:663 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 3 52 theme flow 708:711 arg1 profiles 713:720 laminar flow profiles 700:720 laminar flow profiles 700:720 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 3 53 theme transverse 676:685 arg1 diffusion 687:695 transverse diffusion 676:695 transverse diffusion of laminar flow profiles 676:720 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 4 54 theme sample 819:824 arg1 protocol 836:843 Such a complex sample treatment protocol 804:843 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode 804:912 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode can now be converted into an automated and integrated protocol. 35820058 4 55 theme batchwise 899:907 arg1 mode 909:912 batchwise mode 899:912 batchwise mode 899:912 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode can now be converted into an automated and integrated protocol. 35820058 5 56 theme N-linked 1049:1056 arg1 oligosaccharides 1058:1073 fluorescently labeled N-linked oligosaccharides 1027:1073 fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment 1027:1173 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 3 57 theme fluorescent 632:642 arg1 dye 644:646 fluorescent dye 632:646 fluorescent dye 632:646 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 6 58 theme in-tube 1260:1266 arg1 protocol 1268:1275 the conventional in-tube protocol 1243:1275 the conventional in-tube protocol 1243:1275 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 6 59 theme approach 1229:1236 arg1 superiority 1196:1206 the superiority 1192:1206 the superiority of this in-capillary approach over the conventional in-tube protocol 1192:1275 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 3 60 theme dye 644:646 arg1 injections 618:627 sequential injections 607:627 sequential injections of fluorescent dye and glycan plugs 607:663 This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. 35820058 1 61 theme new 121:123 arg1 approach 125:132 a new approach 119:132 a new approach for in-capillary fluorescent labeling of N-glycans 119:183 In this study, we present a new approach for in-capillary fluorescent labeling of N-glycans prior to their analysis with CE coupled with laser-induced fluorescent detection. 35820058 2 62 theme labeled 504:510 arg1 glycans 512:518 fluorescently labeled glycans 490:518 fluorescently labeled glycans 490:518 This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. 35820058 6 63 theme in-capillary 1216:1227 arg1 approach 1229:1236 this in-capillary approach 1211:1236 this in-capillary approach 1211:1236 We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis. 35820058 4 64 from mode 909:912 arg1 feasible 873:880 feasible 873:880 feasible 873:880 Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode can now be converted into an automated and integrated protocol. 35820058 5 65 link N-linked 1049:1056 arg1 oligosaccharides 1058:1073 fluorescently labeled N-linked oligosaccharides 1027:1073 fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment 1027:1173 Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. 35820058 0 66 theme N-glycans 63:71 arg1 labeling 13:20 capillary labeling 3:20 capillary labeling 3:20 In capillary labeling and online electrophoretic separation of N-glycans from glycoproteins. 35820058 0 66 theme N-glycans 63:71 arg1 separation 49:58 online electrophoretic separation 26:58 online electrophoretic separation of N-glycans from glycoproteins 26:90 In capillary labeling and online electrophoretic separation of N-glycans from glycoproteins. 35820058 1 67 attach present 111:117 arg2 we 108:109 we 108:109 we 108:109 In this study, we present a new approach for in-capillary fluorescent labeling of N-glycans prior to their analysis with CE coupled with laser-induced fluorescent detection. 35820058 1 67 attach present 111:117 arg1 study 101:105 this study 96:105 this study 96:105 In this study, we present a new approach for in-capillary fluorescent labeling of N-glycans prior to their analysis with CE coupled with laser-induced fluorescent detection. 35820058 1 68 theme laser-induced 230:242 arg1 detection 256:264 laser-induced fluorescent detection 230:264 laser-induced fluorescent detection 230:264 In this study, we present a new approach for in-capillary fluorescent labeling of N-glycans prior to their analysis with CE coupled with laser-induced fluorescent detection. 36693100 10 0 theme integral 1489:1496 arg1 structures 1515:1524 Mtb integral membrane protein structures 1485:1524 Mtb integral membrane protein structures 1485:1524 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 36693100 2 1 theme drug 335:338 arg1 resistance 340:349 drug resistance 335:349 drug resistance 335:349 The current treatment regime is long and expensive, and missed doses contribute to drug resistance. 36693100 7 2 gly mannosylated 904:915 arg1 mannosides 971:980 phosphatidyl-myoinositol mannosides 946:980 phosphatidyl-myoinositol mannosides 946:980 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 7 2 gly mannosylated 904:915 arg1 lipids 938:943 mannosylated phosphatidylinositol lipids 904:943 mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids 904:1026 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 12 3 theme mycobacterial 1712:1724 arg1 membrane 1733:1740 the mycobacterial plasma membrane 1708:1740 the mycobacterial plasma membrane 1708:1740 Thus, our work sheds new light on the organization of the mycobacterial plasma membrane. 36693100 5 4 theme Mtb 609:611 arg1 lipids 622:627 Mtb specific lipids 609:627 Mtb specific lipids 609:627 The Mtb cell envelop consists of four distinct layers enriched for Mtb specific lipids and glycans. 36693100 10 5 theme symmetric 1375:1383 arg1 assemblies 1400:1409 both symmetric and asymmetric assemblies 1370:1409 both symmetric and asymmetric assemblies of the Mtb plasma membrane 1370:1436 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 36693100 2 6 theme treatment 264:272 arg1 long 284:287 long 284:287 long 284:287 The current treatment regime is long and expensive, and missed doses contribute to drug resistance. 36693100 2 6 theme treatment 264:272 arg1 regime 274:279 The current treatment regime 252:279 The current treatment regime 252:279 The current treatment regime is long and expensive, and missed doses contribute to drug resistance. 36693100 13 7 theme future 1766:1771 arg1 studies 1773:1779 future studies 1766:1779 future studies on antibiotic development and understanding Mtb membrane protein function 1766:1853 This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function. 36693100 9 8 theme dynamics 1153:1160 arg1 simulations 1167:1177 multiscale molecular dynamics (MD) simulations 1132:1177 multiscale molecular dynamics (MD) simulations 1132:1177 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 9 9 theme MD 1163:1164 arg1 simulations 1167:1177 multiscale molecular dynamics (MD) simulations 1132:1177 multiscale molecular dynamics (MD) simulations 1132:1177 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 7 10 theme lipids 1021:1026 arg1 % 1012:1012 more than 50% 1000:1012 more than 50% of the lipids 1000:1026 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 7 10 theme lipids 1021:1026 arg1 lipids 1021:1026 the lipids 1017:1026 the lipids 1017:1026 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 9 11 theme structure-function 1197:1214 arg1 relationship 1216:1227 the structure-function relationship 1193:1227 the structure-function relationship of the PIM lipid family 1193:1251 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 12 12 theme new 1675:1677 arg1 light 1679:1683 new light 1675:1683 new light 1675:1683 Thus, our work sheds new light on the organization of the mycobacterial plasma membrane. 36693100 8 13 from role 1042:1045 arg1 function 1076:1083 function 1076:1083 function 1076:1083 However, the role of PIMs in the structure and function of the membrane remains elusive. 36693100 8 13 from role 1042:1045 arg1 structure 1062:1070 structure 1062:1070 structure 1062:1070 However, the role of PIMs in the structure and function of the membrane remains elusive. 36693100 1 14 theme causative 163:171 arg1 agent 173:177 the causative agent 159:177 the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually 159:249 Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. 36693100 1 14 theme causative 163:171 arg1 tuberculosis 137:148 Mycobacterium tuberculosis 123:148 Mycobacterium tuberculosis (Mtb) 123:154 Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. 36693100 4 15 theme cell 475:478 arg1 envelope 480:487 a complex cell envelope 465:487 a complex cell envelope that represents a formidable barrier to antibiotics 465:539 Mtb has evolved a complex cell envelope that represents a formidable barrier to antibiotics. 36693100 0 16 theme mycobacterial 92:104 arg1 membrane 113:120 the mycobacterial plasma membrane 88:120 the mycobacterial plasma membrane 88:120 Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane. 36693100 9 17 theme PIM 1236:1238 arg1 family 1246:1251 the PIM lipid family 1232:1251 the PIM lipid family 1232:1251 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 7 18 theme phosphatidylinositol 917:936 arg1 mannosides 971:980 phosphatidyl-myoinositol mannosides 946:980 phosphatidyl-myoinositol mannosides 946:980 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 7 18 theme phosphatidylinositol 917:936 arg1 lipids 938:943 mannosylated phosphatidylinositol lipids 904:943 mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids 904:1026 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 10 19 theme asymmetric 1389:1398 arg1 assemblies 1400:1409 both symmetric and asymmetric assemblies 1370:1409 both symmetric and asymmetric assemblies of the Mtb plasma membrane 1370:1436 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 36693100 9 20 theme family 1246:1251 arg1 relationship 1216:1227 the structure-function relationship 1193:1227 the structure-function relationship of the PIM lipid family 1193:1251 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 6 21 theme outer 655:659 arg1 membrane 661:668 the outer membrane 651:668 the outer membrane 651:668 Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. 36693100 10 22 theme membrane 1429:1436 arg1 assemblies 1400:1409 both symmetric and asymmetric assemblies 1370:1409 both symmetric and asymmetric assemblies of the Mtb plasma membrane 1370:1436 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 36693100 6 23 theme mycolic 684:690 arg1 esters 697:702 mycolic acid esters 684:702 mycolic acid esters 684:702 Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. 36693100 3 24 theme highest 415:421 arg1 priorities 437:446 the highest public health priorities 411:446 the highest public health priorities 411:446 Therefore, development of new anti-TB drugs remains one of the highest public health priorities. 36693100 5 25 theme cell 550:553 arg1 envelop 555:561 The Mtb cell envelop 542:561 The Mtb cell envelop 542:561 The Mtb cell envelop consists of four distinct layers enriched for Mtb specific lipids and glycans. 36693100 10 26 theme Mtb 1418:1420 arg1 membrane 1429:1436 the Mtb plasma membrane 1414:1436 the Mtb plasma membrane 1414:1436 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 36693100 9 27 used used 1127:1130 arg2 we 1124:1125 we 1124:1125 we 1124:1125 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 13 28 theme membrane 1829:1836 arg1 function 1846:1853 Mtb membrane protein function 1825:1853 Mtb membrane protein function 1825:1853 This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function. 36693100 0 29 theme Supramolecular 0:13 arg1 organization 15:26 Supramolecular organization 0:26 Supramolecular organization 0:26 Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane. 36693100 7 30 theme unique 873:878 arg1 composition 886:896 a unique lipid composition 871:896 a unique lipid composition 871:896 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 6 31 theme antibiotic 822:831 arg1 efficacy 833:840 antibiotic efficacy 822:840 antibiotic efficacy 822:840 Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. 36693100 3 32 theme health 430:435 arg1 priorities 437:446 the highest public health priorities 411:446 the highest public health priorities 411:446 Therefore, development of new anti-TB drugs remains one of the highest public health priorities. 36693100 3 33 theme anti-TB 382:388 arg1 drugs 390:394 new anti-TB drugs 378:394 new anti-TB drugs 378:394 Therefore, development of new anti-TB drugs remains one of the highest public health priorities. 36693100 10 34 theme Mtb 1485:1487 arg1 structures 1515:1524 Mtb integral membrane protein structures 1485:1524 Mtb integral membrane protein structures 1485:1524 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 36693100 0 35 theme phosphatidylinositol 57:76 arg1 lipids 78:83 mannosylated phosphatidylinositol lipids 44:83 mannosylated phosphatidylinositol lipids 44:83 Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane. 36693100 8 36 theme PIMs 1050:1053 arg1 role 1042:1045 the role 1038:1045 the role of PIMs in the structure and function of the membrane 1038:1099 However, the role of PIMs in the structure and function of the membrane remains elusive. 36693100 6 37 theme critical 795:802 arg1 role 804:807 a critical role 793:807 a critical role 793:807 Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. 36693100 9 38 theme multiscale 1132:1141 arg1 simulations 1167:1177 multiscale molecular dynamics (MD) simulations 1132:1177 multiscale molecular dynamics (MD) simulations 1132:1177 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 9 39 theme mycobacterial 1328:1340 arg1 membranes 1349:1357 mycobacterial plasma membranes 1328:1357 mycobacterial plasma membranes 1328:1357 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 0 40 gly mannosylated 44:55 arg1 lipids 78:83 mannosylated phosphatidylinositol lipids 44:83 mannosylated phosphatidylinositol lipids 44:83 Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane. 36693100 10 41 theme structures 1515:1524 arg1 distributions 1468:1480 residue distributions 1460:1480 residue distributions of Mtb integral membrane protein structures 1460:1524 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 36693100 9 42 theme membranes 1349:1357 arg1 properties 1314:1323 the biophysical properties 1298:1323 the biophysical properties of mycobacterial plasma membranes 1298:1357 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 10 43 theme membrane 1498:1505 arg1 structures 1515:1524 Mtb integral membrane protein structures 1485:1524 Mtb integral membrane protein structures 1485:1524 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 36693100 11 44 theme known 1568:1572 arg1 drugs 1582:1586 known anti-TB drugs 1568:1586 known anti-TB drugs 1568:1586 To further validate the model, we tested known anti-TB drugs and demonstrated that our models agree with experimental results. 36693100 7 45 theme Mtb 847:849 arg1 membrane 858:865 The Mtb plasma membrane 843:865 The Mtb plasma membrane 843:865 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 13 46 theme antibiotic 1784:1793 arg1 development 1795:1805 antibiotic development 1784:1805 antibiotic development 1784:1805 This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function. 36693100 8 47 theme membrane 1092:1099 arg1 function 1076:1083 function 1076:1083 function 1076:1083 However, the role of PIMs in the structure and function of the membrane remains elusive. 36693100 8 47 theme membrane 1092:1099 arg1 structure 1062:1070 structure 1062:1070 structure 1062:1070 However, the role of PIMs in the structure and function of the membrane remains elusive. 36693100 12 48 theme plasma 1726:1731 arg1 membrane 1733:1740 the mycobacterial plasma membrane 1708:1740 the mycobacterial plasma membrane 1708:1740 Thus, our work sheds new light on the organization of the mycobacterial plasma membrane. 36693100 11 49 theme experimental 1632:1643 arg1 results 1645:1651 experimental results 1632:1651 experimental results 1632:1651 To further validate the model, we tested known anti-TB drugs and demonstrated that our models agree with experimental results. 36693100 6 50 theme plasma 759:764 arg1 membrane 766:773 the plasma membrane 755:773 the plasma membrane 755:773 Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. 36693100 1 51 theme tuberculosis 182:193 arg1 agent 173:177 the causative agent 159:177 the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually 159:249 Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. 36693100 1 51 theme tuberculosis 182:193 arg1 tuberculosis 137:148 Mycobacterium tuberculosis 123:148 Mycobacterium tuberculosis (Mtb) 123:154 Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. 36693100 5 52 theme specific 613:620 arg1 lipids 622:627 Mtb specific lipids 609:627 Mtb specific lipids 609:627 The Mtb cell envelop consists of four distinct layers enriched for Mtb specific lipids and glycans. 36693100 9 53 theme molecular 1143:1151 arg1 simulations 1167:1177 multiscale molecular dynamics (MD) simulations 1132:1177 multiscale molecular dynamics (MD) simulations 1132:1177 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 7 54 with composition 886:896 arg1 mannosides 971:980 phosphatidyl-myoinositol mannosides 946:980 phosphatidyl-myoinositol mannosides 946:980 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 7 54 with composition 886:896 arg1 lipids 938:943 mannosylated phosphatidylinositol lipids 904:943 mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids 904:1026 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 2 55 theme current 256:262 arg1 long 284:287 long 284:287 long 284:287 The current treatment regime is long and expensive, and missed doses contribute to drug resistance. 36693100 2 55 theme current 256:262 arg1 regime 274:279 The current treatment regime 252:279 The current treatment regime 252:279 The current treatment regime is long and expensive, and missed doses contribute to drug resistance. 36693100 5 56 theme Mtb 546:548 arg1 envelop 555:561 The Mtb cell envelop 542:561 The Mtb cell envelop 542:561 The Mtb cell envelop consists of four distinct layers enriched for Mtb specific lipids and glycans. 36693100 0 57 from dynamics 32:39 arg1 membrane 113:120 the mycobacterial plasma membrane 88:120 the mycobacterial plasma membrane 88:120 Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane. 36693100 13 58 theme protein 1838:1844 arg1 function 1846:1853 Mtb membrane protein function 1825:1853 Mtb membrane protein function 1825:1853 This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function. 36693100 0 59 theme plasma 106:111 arg1 membrane 113:120 the mycobacterial plasma membrane 88:120 the mycobacterial plasma membrane 88:120 Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane. 36693100 7 60 theme phosphatidyl-myoinositol 946:969 arg1 mannosides 971:980 phosphatidyl-myoinositol mannosides 946:980 phosphatidyl-myoinositol mannosides 946:980 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 7 60 theme phosphatidyl-myoinositol 946:969 arg1 lipids 938:943 mannosylated phosphatidylinositol lipids 904:943 mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids 904:1026 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 0 61 from organization 15:26 arg1 membrane 113:120 the mycobacterial plasma membrane 88:120 the mycobacterial plasma membrane 88:120 Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane. 36693100 9 62 theme lipid 1240:1244 arg1 family 1246:1251 the PIM lipid family 1232:1251 the PIM lipid family 1232:1251 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 5 63 theme distinct 580:587 arg1 layers 589:594 four distinct layers 575:594 four distinct layers enriched for Mtb specific lipids and glycans 575:639 The Mtb cell envelop consists of four distinct layers enriched for Mtb specific lipids and glycans. 36693100 6 64 theme acid 692:695 arg1 esters 697:702 mycolic acid esters 684:702 mycolic acid esters 684:702 Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. 36693100 7 65 theme mannosylated 904:915 arg1 mannosides 971:980 phosphatidyl-myoinositol mannosides 946:980 phosphatidyl-myoinositol mannosides 946:980 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 7 65 theme mannosylated 904:915 arg1 lipids 938:943 mannosylated phosphatidylinositol lipids 904:943 mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids 904:1026 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 4 66 theme complex 467:473 arg1 envelope 480:487 a complex cell envelope 465:487 a complex cell envelope that represents a formidable barrier to antibiotics 465:539 Mtb has evolved a complex cell envelope that represents a formidable barrier to antibiotics. 36693100 10 67 theme plasma 1422:1427 arg1 membrane 1429:1436 the Mtb plasma membrane 1414:1436 the Mtb plasma membrane 1414:1436 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 36693100 13 68 theme Mtb 1825:1827 arg1 function 1846:1853 Mtb membrane protein function 1825:1853 Mtb membrane protein function 1825:1853 This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function. 36693100 3 69 theme public 423:428 arg1 priorities 437:446 the highest public health priorities 411:446 the highest public health priorities 411:446 Therefore, development of new anti-TB drugs remains one of the highest public health priorities. 36693100 3 70 theme new 378:380 arg1 drugs 390:394 new anti-TB drugs 378:394 new anti-TB drugs 378:394 Therefore, development of new anti-TB drugs remains one of the highest public health priorities. 36693100 7 71 contain has 867:869 arg1 membrane 858:865 The Mtb plasma membrane 843:865 The Mtb plasma membrane 843:865 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 7 71 contain has 867:869 arg2 composition 886:896 a unique lipid composition 871:896 a unique lipid composition 871:896 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 7 72 theme lipid 880:884 arg1 composition 886:896 a unique lipid composition 871:896 a unique lipid composition 871:896 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 1 73 theme Mycobacterium 123:135 arg1 agent 173:177 the causative agent 159:177 the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually 159:249 Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. 36693100 1 73 theme Mycobacterium 123:135 arg1 Mtb 151:153 Mtb 151:153 Mtb 151:153 Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. 36693100 1 73 theme Mycobacterium 123:135 arg1 tuberculosis 137:148 Mycobacterium tuberculosis 123:148 Mycobacterium tuberculosis (Mtb) 123:154 Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. 36693100 13 74 dep development 1795:1805 arg1 function 1846:1853 Mtb membrane protein function 1825:1853 Mtb membrane protein function 1825:1853 This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function. 36693100 7 75 dep mannosides 971:980 arg1 PIMs 983:986 PIMs 983:986 PIMs 983:986 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 0 76 theme mannosylated 44:55 arg1 lipids 78:83 mannosylated phosphatidylinositol lipids 44:83 mannosylated phosphatidylinositol lipids 44:83 Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane. 36693100 4 77 theme formidable 507:516 arg1 barrier 518:524 a formidable barrier 505:524 a formidable barrier to antibiotics 505:539 Mtb has evolved a complex cell envelope that represents a formidable barrier to antibiotics. 36693100 1 78 theme million 228:234 arg1 lives 236:240 ~1.6 million lives 223:240 ~1.6 million lives 223:240 Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. 36693100 3 79 theme priorities 437:446 arg1 priorities 437:446 the highest public health priorities 411:446 the highest public health priorities 411:446 Therefore, development of new anti-TB drugs remains one of the highest public health priorities. 36693100 3 79 theme priorities 437:446 arg1 one 404:406 one 404:406 one 404:406 Therefore, development of new anti-TB drugs remains one of the highest public health priorities. 36693100 0 80 theme lipids 78:83 arg1 dynamics 32:39 dynamics 32:39 dynamics 32:39 Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane. 36693100 0 80 theme lipids 78:83 arg1 organization 15:26 Supramolecular organization 0:26 Supramolecular organization 0:26 Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane. 36693100 9 81 theme biophysical 1302:1312 arg1 properties 1314:1323 the biophysical properties 1298:1323 the biophysical properties of mycobacterial plasma membranes 1298:1357 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 13 82 from studies 1773:1779 arg1 understanding 1811:1823 understanding 1811:1823 understanding 1811:1823 This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function. 36693100 13 82 from studies 1773:1779 arg1 development 1795:1805 antibiotic development 1784:1805 antibiotic development 1784:1805 This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function. 36693100 3 83 theme drugs 390:394 arg1 development 363:373 development 363:373 development of new anti-TB drugs 363:394 Therefore, development of new anti-TB drugs remains one of the highest public health priorities. 36693100 10 84 theme residue 1460:1466 arg1 distributions 1468:1480 residue distributions 1460:1480 residue distributions of Mtb integral membrane protein structures 1460:1524 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 36693100 11 85 theme anti-TB 1574:1580 arg1 drugs 1582:1586 known anti-TB drugs 1568:1586 known anti-TB drugs 1568:1586 To further validate the model, we tested known anti-TB drugs and demonstrated that our models agree with experimental results. 36693100 2 86 theme missed 308:313 arg1 doses 315:319 missed doses 308:319 missed doses 308:319 The current treatment regime is long and expensive, and missed doses contribute to drug resistance. 36693100 7 87 theme plasma 851:856 arg1 membrane 858:865 The Mtb plasma membrane 843:865 The Mtb plasma membrane 843:865 The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. 36693100 9 88 theme plasma 1342:1347 arg1 membranes 1349:1357 mycobacterial plasma membranes 1328:1357 mycobacterial plasma membranes 1328:1357 Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. 36693100 12 89 theme membrane 1733:1740 arg1 organization 1692:1703 the organization 1688:1703 the organization of the mycobacterial plasma membrane 1688:1740 Thus, our work sheds new light on the organization of the mycobacterial plasma membrane. 36693100 10 90 theme protein 1507:1513 arg1 structures 1515:1524 Mtb integral membrane protein structures 1485:1524 Mtb integral membrane protein structures 1485:1524 We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. 37372566 4 0 theme chemical 784:791 arg1 analysis 805:812 basic chemical composition analysis 778:812 basic chemical composition analysis 778:812 Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. 37372566 9 1 theme aqueous 1729:1735 arg1 extract 1737:1743 FCPP aqueous extract 1724:1743 FCPP aqueous extract 1724:1743 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 3 2 theme gastric 595:601 arg1 model 613:617 acute alcoholic gastric ulcer rat model 579:617 acute alcoholic gastric ulcer rat model 579:617 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 2 3 theme FCPP 311:314 arg1 protection 297:306 the gastric mucosa protection 278:306 the gastric mucosa protection of FCPP 278:314 However, the gastric mucosa protection of FCPP has not been reported yet, and its effective mechanism is unclear. 37372566 7 4 theme dismutase 1356:1364 arg1 activity 1372:1379 superoxide dismutase (SOD) activity 1345:1379 superoxide dismutase (SOD) activity 1345:1379 Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. 37372566 6 5 theme ulcer 1076:1080 arg1 index 1082:1086 The ulcer index 1072:1086 The ulcer index of gastric tissue induced by alcohol 1072:1123 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 11 6 theme new 2463:2465 arg1 products 2467:2474 new products 2463:2474 new products of FCPP 2463:2482 This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP. 37372566 9 7 theme mucosa 1964:1969 arg1 dependent 2026:2034 dependent 2026:2034 dependent 2026:2034 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 9 7 theme mucosa 1964:1969 arg1 effects 1982:1988 the gastric mucosa protection effects 1952:1988 the gastric mucosa protection effects of FCPP aqueous extract 1952:2012 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 4 8 theme scratch 761:767 arg1 test 769:772 a GES-1 scratch test 753:772 a GES-1 scratch test 753:772 Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. 37372566 3 9 from mechanism 413:421 arg1 mucosa 458:463 gastric mucosa 450:463 gastric mucosa 450:463 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 1 10 theme pickled 166:172 arg1 products 174:181 Finger citron pickled products 152:181 Finger citron pickled products (FCPP) 152:188 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 1 10 theme pickled 166:172 arg1 FCPP 184:187 FCPP 184:187 FCPP 184:187 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 9 11 theme FCPP 1993:1996 arg1 extract 2006:2012 FCPP aqueous extract 1993:2012 FCPP aqueous extract 1993:2012 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 6 12 contain had 1247:1249 arg1 extract 1239:1245 FCPP aqueous extract 1226:1245 FCPP aqueous extract 1226:1245 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 6 12 contain had 1247:1249 arg2 effect 1269:1274 a good protective effect 1251:1274 a good protective effect 1251:1274 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 9 13 theme factor 1785:1790 arg1 protein 1812:1818 nuclear factor kappa-B (NF-κB/P65) protein 1777:1818 nuclear factor kappa-B (NF-κB/P65) protein 1777:1818 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 9 14 theme extract 2006:2012 arg1 dependent 2026:2034 dependent 2026:2034 dependent 2026:2034 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 9 14 theme extract 2006:2012 arg1 effects 1982:1988 the gastric mucosa protection effects 1952:1988 the gastric mucosa protection effects of FCPP aqueous extract 1952:2012 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 0 15 theme In 122:123 arg1 Studies 143:149 In Vitro and In Vivo Studies 122:149 In Vitro and In Vivo Studies 122:149 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 8 16 theme rats 1610:1613 arg1 serum 1601:1605 serum 1601:1605 serum of rats 1601:1613 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 10 17 theme cell 2209:2212 arg1 assay 2222:2226 GES-1 cell scratch assay 2203:2226 GES-1 cell scratch assay 2203:2226 The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. 37372566 11 18 theme promising 2286:2294 arg1 potential 2296:2304 promising potential 2286:2304 promising potential 2286:2304 This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP. 37372566 9 19 theme gastric 1956:1962 arg1 dependent 2026:2034 dependent 2026:2034 dependent 2026:2034 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 9 19 theme gastric 1956:1962 arg1 effects 1982:1988 the gastric mucosa protection effects 1952:1988 the gastric mucosa protection effects of FCPP aqueous extract 1952:2012 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 6 20 theme FCPP 1188:1191 arg1 extract 1201:1207 FCPP aqueous extract 1188:1207 FCPP aqueous extract 1188:1207 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 5 21 theme factor 963:968 arg1 secretion 913:921 the secretion 909:921 the secretion of trefoil factor thyroid transcription factor 2 (TFF2) 909:977 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 3 22 theme first 511:515 arg1 time 517:520 the first time 507:520 the first time 507:520 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 6 23 theme tissue 1099:1104 arg1 index 1082:1086 The ulcer index 1072:1086 The ulcer index of gastric tissue induced by alcohol 1072:1123 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 9 24 theme NF-κB/caspase-1/IL-1β 2043:2063 arg1 axis 2065:2068 the NF-κB/caspase-1/IL-1β axis 2039:2068 the NF-κB/caspase-1/IL-1β axis 2039:2068 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 3 25 theme mucosa 543:548 arg1 GES-1 568:572 GES-1 568:572 GES-1 568:572 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 3 25 theme mucosa 543:548 arg1 cells 561:565 human gastric mucosa epithelial cells 529:565 human gastric mucosa epithelial cells (GES-1) 529:573 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 8 26 dep cytokines 1533:1541 arg1 cytokines 1533:1541 cytokines 1533:1541 cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) 1533:1596 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 8 26 dep cytokines 1533:1541 arg1 TNF-α 1543:1547 TNF-α 1543:1547 TNF-α 1543:1547 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 8 26 dep cytokines 1533:1541 arg1 interleukin-6 1577:1589 interleukin-6 1577:1589 interleukin-6 (IL-6) 1577:1596 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 8 26 dep cytokines 1533:1541 arg1 interleukin-1β 1550:1563 interleukin-1β 1550:1563 interleukin-1β (IL-1β) 1550:1571 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 8 26 dep cytokines 1533:1541 arg1 IL-6 1592:1595 IL-6 1592:1595 IL-6 1592:1595 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 8 26 dep cytokines 1533:1541 arg1 IL-1β 1566:1570 IL-1β 1566:1570 IL-1β 1566:1570 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 6 27 theme protective 1258:1267 arg1 effect 1269:1274 a good protective effect 1251:1274 a good protective effect 1251:1274 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 5 28 theme factor-α 1026:1033 arg1 secretion 998:1006 the secretion 994:1006 the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol 994:1069 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 3 29 theme human 529:533 arg1 GES-1 568:572 GES-1 568:572 GES-1 568:572 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 3 29 theme human 529:533 arg1 cells 561:565 human gastric mucosa epithelial cells 529:565 human gastric mucosa epithelial cells (GES-1) 529:573 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 5 30 theme FCPP 815:818 arg1 extract 828:834 FCPP aqueous extract 815:834 FCPP aqueous extract 815:834 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 11 31 theme gastric 2348:2354 arg1 ulcers 2356:2361 gastric ulcers 2348:2361 gastric ulcers 2348:2361 This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP. 37372566 9 32 theme IL-1β 1843:1847 arg1 protein 1849:1855 IL-1β protein 1843:1855 IL-1β protein 1843:1855 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 0 33 theme Products 73:80 arg1 Extract 40:46 the Aqueous Extract 28:46 the Aqueous Extract of Finger Citron Pickled Products 28:80 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 8 34 theme cytokines 1662:1670 arg1 increase 1632:1639 the increase 1628:1639 the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent 1628:1708 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 1 35 theme Finger 152:157 arg1 products 174:181 Finger citron pickled products 152:181 Finger citron pickled products (FCPP) 152:188 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 1 35 theme Finger 152:157 arg1 FCPP 184:187 FCPP 184:187 FCPP 184:187 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 7 36 theme good 1435:1438 arg1 capacity 1452:1459 good antioxidant capacity 1435:1459 good antioxidant capacity 1435:1459 Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. 37372566 11 37 theme gastric 2320:2326 arg1 mucosa 2328:2333 gastric mucosa 2320:2333 gastric mucosa 2320:2333 This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP. 37372566 0 38 theme Ethanol-Induced 90:104 arg1 Damage 114:119 Ethanol-Induced Gastric Damage 90:119 Ethanol-Induced Gastric Damage 90:119 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 4 39 from substances 676:685 arg1 extract 702:708 the aqueous extract 690:708 the aqueous extract that exert gastroprotective activity 690:745 Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. 37372566 9 40 theme gastric 1864:1870 arg1 tissue 1872:1877 the gastric tissue 1860:1877 the gastric tissue of rats 1860:1885 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 6 41 theme FCPP 1226:1229 arg1 extract 1239:1245 FCPP aqueous extract 1226:1245 FCPP aqueous extract 1226:1245 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 5 42 theme tumor 1011:1015 arg1 TNF-α 1036:1040 TNF-α 1036:1040 TNF-α 1036:1040 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 5 42 theme tumor 1011:1015 arg1 factor-α 1026:1033 tumor necrosis factor-α 1011:1033 tumor necrosis factor-α (TNF-α) 1011:1041 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 10 43 theme FCPP 2094:2097 arg1 extract 2107:2113 FCPP aqueous extract 2094:2113 FCPP aqueous extract 2094:2113 The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. 37372566 0 44 theme Gastroprotective 0:15 arg1 Effects 17:23 Gastroprotective Effects 0:23 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage 0:119 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 5 45 theme protective 856:865 arg1 role 882:885 a protective and reparative role 854:885 a protective and reparative role 854:885 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 9 46 theme protein 1831:1837 arg1 expression 1763:1772 the expression 1759:1772 the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein 1759:1855 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 1 47 theme gastric 253:259 arg1 mucosa 261:266 gastric mucosa 253:266 gastric mucosa 253:266 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 11 48 theme aqueous 2260:2266 arg1 extract 2268:2274 FCPP aqueous extract 2255:2274 FCPP aqueous extract 2255:2274 This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP. 37372566 5 49 theme reparative 871:880 arg1 role 882:885 a protective and reparative role 854:885 a protective and reparative role 854:885 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 9 50 theme kappa-B 1792:1798 arg1 protein 1812:1818 nuclear factor kappa-B (NF-κB/P65) protein 1777:1818 nuclear factor kappa-B (NF-κB/P65) protein 1777:1818 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 2 51 theme effective 351:359 arg1 mechanism 361:369 its effective mechanism 347:369 its effective mechanism 347:369 However, the gastric mucosa protection of FCPP has not been reported yet, and its effective mechanism is unclear. 37372566 0 52 theme Aqueous 32:38 arg1 Extract 40:46 the Aqueous Extract 28:46 the Aqueous Extract of Finger Citron Pickled Products 28:80 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 6 53 theme stomach 1283:1289 arg1 mucosa 1291:1296 the stomach mucosa 1279:1296 the stomach mucosa 1279:1296 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 7 54 theme malondialdehyde 1393:1407 arg1 content 1415:1421 malondialdehyde (MDA) content 1393:1421 malondialdehyde (MDA) content 1393:1421 Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. 37372566 5 55 theme factor 934:939 arg1 factor 963:968 trefoil factor thyroid transcription factor 2 926:970 trefoil factor thyroid transcription factor 2 (TFF2) 926:977 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 5 55 theme factor 934:939 arg1 TFF2 973:976 TFF2 973:976 TFF2 973:976 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 0 56 theme Citron 58:63 arg1 Products 73:80 Finger Citron Pickled Products 51:80 Finger Citron Pickled Products 51:80 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 3 57 theme FCPP 426:429 arg1 extract 439:445 FCPP aqueous extract 426:445 FCPP aqueous extract 426:445 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 5 58 theme transcription 949:961 arg1 factor 963:968 trefoil factor thyroid transcription factor 2 926:970 trefoil factor thyroid transcription factor 2 (TFF2) 926:977 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 5 58 theme transcription 949:961 arg1 TFF2 973:976 TFF2 973:976 TFF2 973:976 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 3 59 theme alcoholic 585:593 arg1 model 613:617 acute alcoholic gastric ulcer rat model 579:617 acute alcoholic gastric ulcer rat model 579:617 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 2 60 theme mucosa 290:295 arg1 protection 297:306 the gastric mucosa protection 278:306 the gastric mucosa protection of FCPP 278:314 However, the gastric mucosa protection of FCPP has not been reported yet, and its effective mechanism is unclear. 37372566 1 61 theme folk 194:197 arg1 remedies 199:206 folk remedies 194:206 folk remedies 194:206 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 3 62 theme gastric 450:456 arg1 mucosa 458:463 gastric mucosa 450:463 gastric mucosa 450:463 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 8 63 theme cytokines 1533:1541 arg1 increase 1521:1528 the increase 1517:1528 the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats 1517:1613 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 9 64 theme FCPP 1724:1727 arg1 extract 1737:1743 FCPP aqueous extract 1724:1743 FCPP aqueous extract 1724:1743 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 8 65 theme FCPP 1481:1484 arg1 extract 1470:1476 Aqueous extract 1462:1476 Aqueous extract of FCPP 1462:1484 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 3 66 theme extract 439:445 arg1 mechanism 413:421 the protective mechanism 398:421 the protective mechanism of FCPP aqueous extract on gastric mucosa 398:463 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 7 67 theme superoxide 1345:1354 arg1 dismutase 1356:1364 superoxide dismutase 1345:1364 superoxide dismutase (SOD) activity 1345:1379 Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. 37372566 7 67 theme superoxide 1345:1354 arg1 SOD 1367:1369 SOD 1367:1369 SOD 1367:1369 Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. 37372566 4 68 theme basic 778:782 arg1 analysis 805:812 basic chemical composition analysis 778:812 basic chemical composition analysis 778:812 Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. 37372566 11 69 theme FCPP 2479:2482 arg1 products 2467:2474 new products 2463:2474 new products of FCPP 2463:2482 This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP. 37372566 3 70 theme ulcer 603:607 arg1 model 613:617 acute alcoholic gastric ulcer rat model 579:617 acute alcoholic gastric ulcer rat model 579:617 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 1 71 theme southern 223:230 arg1 China 232:236 southern China 223:236 southern China 223:236 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 4 72 theme composition 793:803 arg1 analysis 805:812 basic chemical composition analysis 778:812 basic chemical composition analysis 778:812 Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. 37372566 7 73 theme FCPP 1309:1312 arg1 extract 1322:1328 FCPP aqueous extract 1309:1328 FCPP aqueous extract 1309:1328 Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. 37372566 9 74 theme protection 1971:1980 arg1 dependent 2026:2034 dependent 2026:2034 dependent 2026:2034 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 9 74 theme protection 1971:1980 arg1 effects 1982:1988 the gastric mucosa protection effects 1952:1988 the gastric mucosa protection effects of FCPP aqueous extract 1952:2012 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 6 75 theme p 1154:1154 arg1 < 1156:1156 p < 0.01 1154:1161 p < 0.01 1154:1161 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 1 76 theme citron 159:164 arg1 products 174:181 Finger citron pickled products 152:181 Finger citron pickled products (FCPP) 152:188 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 1 76 theme citron 159:164 arg1 FCPP 184:187 FCPP 184:187 FCPP 184:187 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 7 77 theme aqueous 1314:1320 arg1 extract 1322:1328 FCPP aqueous extract 1309:1328 FCPP aqueous extract 1309:1328 Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. 37372566 4 78 theme GES-1 755:759 arg1 test 769:772 a GES-1 scratch test 753:772 a GES-1 scratch test 753:772 Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. 37372566 10 79 theme scratch 2214:2220 arg1 assay 2222:2226 GES-1 cell scratch assay 2203:2226 GES-1 cell scratch assay 2203:2226 The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. 37372566 10 80 theme main 2128:2131 arg1 components 2133:2142 the main components 2124:2142 the main components that exerted gastroprotective activity 2124:2181 The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. 37372566 10 80 theme main 2128:2131 arg1 polysaccharides 2075:2089 The polysaccharides 2071:2089 The polysaccharides in FCPP aqueous extract 2071:2113 The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. 37372566 9 81 theme nuclear 1777:1783 arg1 protein 1812:1818 nuclear factor kappa-B (NF-κB/P65) protein 1777:1818 nuclear factor kappa-B (NF-κB/P65) protein 1777:1818 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 9 82 theme aqueous 1998:2004 arg1 extract 2006:2012 FCPP aqueous extract 1993:2012 FCPP aqueous extract 1993:2012 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 6 83 with pretreatment 1170:1181 arg1 extract 1201:1207 FCPP aqueous extract 1188:1207 FCPP aqueous extract 1188:1207 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 11 84 theme experimental 2387:2398 arg1 basis 2400:2404 an experimental basis 2384:2404 an experimental basis for further utilizing the medicinal value and developing new products of FCPP 2384:2482 This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP. 37372566 0 85 dep In 122:123 arg1 Vitro 125:129 Vitro 125:129 Vitro 125:129 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 8 86 dep cytokines 1662:1670 arg1 interleukin-10 1672:1685 interleukin-10 1672:1685 anti-inflammatory cytokines interleukin-10 (IL-10) 1644:1693 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 8 86 dep cytokines 1662:1670 arg1 IL-10 1688:1692 IL-10 1688:1692 IL-10 1688:1692 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 1 87 from famous 213:218 arg1 China 232:236 southern China 223:236 southern China 223:236 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 10 88 theme gastroprotective 2157:2172 arg1 activity 2174:2181 gastroprotective activity 2157:2181 gastroprotective activity 2157:2181 The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. 37372566 9 89 theme NF-κB/P65 1801:1809 arg1 protein 1812:1818 nuclear factor kappa-B (NF-κB/P65) protein 1777:1818 nuclear factor kappa-B (NF-κB/P65) protein 1777:1818 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 6 90 theme aqueous 1193:1199 arg1 extract 1201:1207 FCPP aqueous extract 1188:1207 FCPP aqueous extract 1188:1207 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 10 91 theme GES-1 2203:2207 arg1 assay 2222:2226 GES-1 cell scratch assay 2203:2226 GES-1 cell scratch assay 2203:2226 The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. 37372566 9 92 theme IκBα 1922:1925 arg1 protein 1927:1933 IκBα protein 1922:1933 IκBα protein 1922:1933 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 9 93 theme protein 1812:1818 arg1 expression 1763:1772 the expression 1759:1772 the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein 1759:1855 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 11 94 theme FCPP 2255:2258 arg1 extract 2268:2274 FCPP aqueous extract 2255:2274 FCPP aqueous extract 2255:2274 This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP. 37372566 3 95 theme gastric 535:541 arg1 GES-1 568:572 GES-1 568:572 GES-1 568:572 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 3 95 theme gastric 535:541 arg1 cells 561:565 human gastric mucosa epithelial cells 529:565 human gastric mucosa epithelial cells (GES-1) 529:573 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 0 96 dep Studies 143:149 arg1 Effects 17:23 Gastroprotective Effects 0:23 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage 0:119 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 6 97 theme gastric 1091:1097 arg1 tissue 1099:1104 gastric tissue 1091:1104 gastric tissue 1091:1104 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 9 98 theme caspase-1 1821:1829 arg1 protein 1831:1837 caspase-1 protein 1821:1837 caspase-1 protein 1821:1837 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 0 99 theme Pickled 65:71 arg1 Products 73:80 Finger Citron Pickled Products 51:80 Finger Citron Pickled Products 51:80 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 0 100 dep In 135:136 arg1 Vivo 138:141 Vivo 138:141 Vivo 138:141 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 7 101 theme antioxidant 1440:1450 arg1 capacity 1452:1459 good antioxidant capacity 1435:1459 good antioxidant capacity 1435:1459 Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. 37372566 10 102 from polysaccharides 2075:2089 arg1 extract 2107:2113 FCPP aqueous extract 2094:2113 FCPP aqueous extract 2094:2113 The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. 37372566 6 103 theme good 1253:1256 arg1 effect 1269:1274 a good protective effect 1251:1274 a good protective effect 1251:1274 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 5 104 theme aqueous 820:826 arg1 extract 828:834 FCPP aqueous extract 815:834 FCPP aqueous extract 815:834 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 1 105 from China 232:236 arg1 famous 213:218 famous 213:218 famous 213:218 Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. 37372566 9 106 theme protein 1849:1855 arg1 expression 1763:1772 the expression 1759:1772 the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein 1759:1855 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 0 107 theme Gastric 106:112 arg1 Damage 114:119 Ethanol-Induced Gastric Damage 90:119 Ethanol-Induced Gastric Damage 90:119 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 8 108 theme anti-inflammatory 1644:1660 arg1 cytokines 1662:1670 anti-inflammatory cytokines 1644:1670 anti-inflammatory cytokines interleukin-10 (IL-10) 1644:1693 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 4 109 theme main 671:674 arg1 substances 676:685 the main substances 667:685 the main substances in the aqueous extract that exert gastroprotective activity 667:745 Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. 37372566 6 110 theme aqueous 1231:1237 arg1 extract 1239:1245 FCPP aqueous extract 1226:1245 FCPP aqueous extract 1226:1245 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 10 111 theme aqueous 2099:2105 arg1 extract 2107:2113 FCPP aqueous extract 2094:2113 FCPP aqueous extract 2094:2113 The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. 37372566 8 112 from increase 1521:1528 arg1 serum 1601:1605 serum 1601:1605 serum of rats 1601:1613 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 5 113 theme necrosis 1017:1024 arg1 TNF-α 1036:1040 TNF-α 1036:1040 TNF-α 1036:1040 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 5 113 theme necrosis 1017:1024 arg1 factor-α 1026:1033 tumor necrosis factor-α 1011:1033 tumor necrosis factor-α (TNF-α) 1011:1041 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 0 114 theme In 135:136 arg1 Studies 143:149 In Vitro and In Vivo Studies 122:149 In Vitro and In Vivo Studies 122:149 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 9 115 theme rats 1882:1885 arg1 tissue 1872:1877 the gastric tissue 1860:1877 the gastric tissue of rats 1860:1885 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 5 116 from secretion 998:1006 arg1 cells 1046:1050 cells 1046:1050 cells damaged by alcohol 1046:1069 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 3 117 theme protective 402:411 arg1 mechanism 413:421 the protective mechanism 398:421 the protective mechanism of FCPP aqueous extract on gastric mucosa 398:463 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 0 118 theme Extract 40:46 arg1 Effects 17:23 Gastroprotective Effects 0:23 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage 0:119 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 5 119 theme trefoil 926:932 arg1 factor 963:968 trefoil factor thyroid transcription factor 2 926:970 trefoil factor thyroid transcription factor 2 (TFF2) 926:977 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 5 119 theme trefoil 926:932 arg1 TFF2 973:976 TFF2 973:976 TFF2 973:976 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 3 120 theme epithelial 550:559 arg1 GES-1 568:572 GES-1 568:572 GES-1 568:572 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 3 120 theme epithelial 550:559 arg1 cells 561:565 human gastric mucosa epithelial cells 529:565 human gastric mucosa epithelial cells (GES-1) 529:573 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 4 121 theme gastroprotective 721:736 arg1 activity 738:745 gastroprotective activity 721:745 gastroprotective activity 721:745 Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. 37372566 0 122 theme Finger 51:56 arg1 Products 73:80 Finger Citron Pickled Products 51:80 Finger Citron Pickled Products 51:80 Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies. 37372566 5 123 theme thyroid 941:947 arg1 factor 963:968 trefoil factor thyroid transcription factor 2 926:970 trefoil factor thyroid transcription factor 2 (TFF2) 926:977 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 5 123 theme thyroid 941:947 arg1 TFF2 973:976 TFF2 973:976 TFF2 973:976 FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. 37372566 8 124 theme Aqueous 1462:1468 arg1 extract 1470:1476 Aqueous extract 1462:1476 Aqueous extract of FCPP 1462:1484 Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. 37372566 3 125 theme acute 579:583 arg1 model 613:617 acute alcoholic gastric ulcer rat model 579:617 acute alcoholic gastric ulcer rat model 579:617 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 3 126 theme aqueous 431:437 arg1 extract 439:445 FCPP aqueous extract 426:445 FCPP aqueous extract 426:445 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 37372566 9 127 theme protein 1927:1933 arg1 expression 1908:1917 the expression 1904:1917 the expression of IκBα protein 1904:1933 Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. 37372566 4 128 theme aqueous 694:700 arg1 extract 702:708 the aqueous extract 690:708 the aqueous extract that exert gastroprotective activity 690:745 Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. 37372566 2 129 theme gastric 282:288 arg1 protection 297:306 the gastric mucosa protection 278:306 the gastric mucosa protection of FCPP 278:314 However, the gastric mucosa protection of FCPP has not been reported yet, and its effective mechanism is unclear. 37372566 6 130 dep decreased 1143:1151 arg1 < 1156:1156 p < 0.01 1154:1161 p < 0.01 1154:1161 The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. 37372566 11 131 theme medicinal 2432:2440 arg1 value 2442:2446 the medicinal value 2428:2446 the medicinal value 2428:2446 This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP. 37372566 3 132 theme rat 609:611 arg1 model 613:617 acute alcoholic gastric ulcer rat model 579:617 acute alcoholic gastric ulcer rat model 579:617 In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. 36613996 6 0 theme trichomes 861:869 arg1 cells 903:907 transfer cells 894:907 transfer cells 894:907 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 0 theme trichomes 861:869 arg1 cells 848:852 internal head cells 834:852 internal head cells 834:852 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 0 theme trichomes 861:869 arg1 idea 932:935 the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes 928:1019 the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes 928:1019 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 0 theme trichomes 861:869 arg1 cells 824:828 The endodermal cells 809:828 The endodermal cells 809:828 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 7 1 theme walls 1077:1081 arg1 composition 1051:1061 the composition 1047:1061 the composition of their cell walls 1047:1081 Trichome cells differ in the composition of their cell walls, e.g., the cell walls of the internal head cells are enriched with arabinogalactan proteins (AGPs). 36613996 6 2 theme head 843:846 arg1 cells 903:907 transfer cells 894:907 transfer cells 894:907 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 2 theme head 843:846 arg1 cells 848:852 internal head cells 834:852 internal head cells 834:852 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 2 theme head 843:846 arg1 idea 932:935 the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes 928:1019 the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes 928:1019 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 2 theme head 843:846 arg1 cells 824:828 The endodermal cells 809:828 The endodermal cells 809:828 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 4 3 theme electron 597:604 arg1 microscopy 606:615 electron microscopy 597:615 electron microscopy 597:615 Light and electron microscopy was used to show the trichomes' structure. 36613996 1 4 theme abaxial 152:158 arg1 glands 161:166 external (abaxial) glands 142:166 external (abaxial) glands 142:166 The digestive organs of carnivorous plants have external (abaxial) glands and trichomes, which perform various functions. 36613996 5 5 gly glycoproteins 794:806 arg1 glycoproteins 794:806 glycoproteins 794:806 glycoproteins 794:806 Fluorescence microscopy was used to locate the carbohydrate epitopes that are associated with the major cell wall polysaccharides and glycoproteins. 36613996 2 6 theme model 265:269 arg1 Ellis 234:238 Dionaea muscipula Ellis 216:238 Dionaea muscipula Ellis (the Venus flytrap) 216:258 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 2 6 theme model 265:269 arg1 species 289:295 a model carnivorous plant species 263:295 a model carnivorous plant species whose traps are covered by external trichomes 263:341 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 12 7 theme mature 1792:1797 arg1 hydathodes 1836:1845 hydathodes 1836:1845 hydathodes 1836:1845 This may suggest that mature stellate trichomes might function as hydathodes, but this should be experimentally proven. 36613996 12 7 theme mature 1792:1797 arg1 trichomes 1808:1816 mature stellate trichomes 1792:1816 mature stellate trichomes 1792:1816 This may suggest that mature stellate trichomes might function as hydathodes, but this should be experimentally proven. 36613996 8 8 from poor 1226:1229 arg1 HGs 1273:1275 HGs 1273:1275 HGs 1273:1275 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 8 from poor 1226:1229 arg1 homogalacturonans 1254:1270 both low and highly homogalacturonans 1234:1270 both low and highly homogalacturonans (HGs) 1234:1276 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 9 theme cell 1187:1190 arg1 poor 1226:1229 poor 1226:1229 poor 1226:1229 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 9 theme cell 1187:1190 arg1 walls 1192:1196 The cell walls 1183:1196 The cell walls of the outer head cells 1183:1220 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 11 10 theme secondary 1625:1633 arg1 cell 1640:1643 a thick secondary wall cell 1617:1643 a thick secondary wall cell 1617:1643 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 8 11 from rich 1310:1313 arg1 polysaccharide 1329:1342 the pectic polysaccharide 1318:1342 the pectic polysaccharide (1-4)-β-D-galactan 1318:1361 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 12 theme pectic 1322:1327 arg1 polysaccharide 1329:1342 the pectic polysaccharide 1318:1342 the pectic polysaccharide (1-4)-β-D-galactan 1318:1361 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 3 13 theme authors 543:549 arg1 suggestions 522:532 the suggestions 518:532 the suggestions of other authors about the roles of these trichomes 518:584 The aim of the study was to fill in the gap regarding the structure of the stellate outer trichomes and their immunocytochemistry and to determine whether these data support the suggestions of other authors about the roles of these trichomes. 36613996 6 14 theme transfer 894:901 arg1 cells 848:852 internal head cells 834:852 internal head cells 834:852 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 14 theme transfer 894:901 arg1 cells 903:907 transfer cells 894:907 transfer cells 894:907 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 14 theme transfer 894:901 arg1 idea 932:935 the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes 928:1019 the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes 928:1019 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 14 theme transfer 894:901 arg1 cells 824:828 The endodermal cells 809:828 The endodermal cells 809:828 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 10 15 theme outer 1562:1566 arg1 head 1568:1571 the outer head 1558:1571 the outer head 1558:1571 However, the role of these trichomes is different when the outer head cells collapse. 36613996 8 16 theme outer 1205:1209 arg1 cells 1216:1220 the outer head cells 1201:1220 the outer head cells 1201:1220 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 11 17 theme space 1763:1767 arg1 role 1736:1739 the role 1732:1739 the role of a large apoplastic space 1732:1767 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 1 18 theme digestive 98:106 arg1 organs 108:113 The digestive organs 94:113 The digestive organs of carnivorous plants 94:135 The digestive organs of carnivorous plants have external (abaxial) glands and trichomes, which perform various functions. 36613996 8 19 theme cells 1216:1220 arg1 poor 1226:1229 poor 1226:1229 poor 1226:1229 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 19 theme cells 1216:1220 arg1 walls 1192:1196 The cell walls 1183:1196 The cell walls of the outer head cells 1183:1220 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 11 20 theme internal 1596:1603 arg1 cells 1610:1614 the internal head cells 1592:1614 the internal head cells 1592:1614 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 2 21 theme Dionaea 216:222 arg1 flytrap 251:257 the Venus flytrap 241:257 the Venus flytrap 241:257 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 2 21 theme Dionaea 216:222 arg1 Ellis 234:238 Dionaea muscipula Ellis 216:238 Dionaea muscipula Ellis (the Venus flytrap) 216:258 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 2 21 theme Dionaea 216:222 arg1 species 289:295 a model carnivorous plant species 263:295 a model carnivorous plant species whose traps are covered by external trichomes 263:341 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 9 22 theme stellate 1393:1400 arg1 trichomes 1402:1410 young stellate trichomes 1387:1410 young stellate trichomes 1387:1410 In the immature traps, young stellate trichomes produce mucilage which may protect the trap surface, and in particular, the trap entrance. 36613996 5 23 theme carbohydrate 707:718 arg1 epitopes 720:727 the carbohydrate epitopes 703:727 the carbohydrate epitopes that are associated with the major cell wall polysaccharides and glycoproteins 703:806 Fluorescence microscopy was used to locate the carbohydrate epitopes that are associated with the major cell wall polysaccharides and glycoproteins. 36613996 1 24 theme external 142:149 arg1 glands 161:166 external (abaxial) glands 142:166 external (abaxial) glands 142:166 The digestive organs of carnivorous plants have external (abaxial) glands and trichomes, which perform various functions. 36613996 11 25 theme large 1746:1750 arg1 space 1763:1767 a large apoplastic space 1744:1767 a large apoplastic space 1744:1767 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 7 26 theme head 1121:1124 arg1 cells 1126:1130 the internal head cells 1108:1130 the internal head cells 1108:1130 Trichome cells differ in the composition of their cell walls, e.g., the cell walls of the internal head cells are enriched with arabinogalactan proteins (AGPs). 36613996 11 27 theme head 1714:1717 arg1 cells 1719:1723 the outer head cells 1704:1723 the outer head cells 1704:1723 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 0 28 theme Stellate 0:7 arg1 Trichomes 9:17 Stellate Trichomes 0:17 Stellate Trichomes in Dionaea muscipula Ellis (Venus Flytrap) Traps, Structure and Functions. 0:92 Stellate Trichomes in Dionaea muscipula Ellis (Venus Flytrap) Traps, Structure and Functions. 36613996 4 29 used used 621:624 arg2 microscopy 606:615 electron microscopy 597:615 electron microscopy 597:615 Light and electron microscopy was used to show the trichomes' structure. 36613996 4 29 used used 621:624 arg2 Light 587:591 Light 587:591 Light 587:591 Light and electron microscopy was used to show the trichomes' structure. 36613996 9 30 theme trap 1451:1454 arg1 surface 1456:1462 the trap surface 1447:1462 the trap surface 1447:1462 In the immature traps, young stellate trichomes produce mucilage which may protect the trap surface, and in particular, the trap entrance. 36613996 5 31 theme cell 764:767 arg1 polysaccharides 774:788 the major cell wall polysaccharides 754:788 the major cell wall polysaccharides 754:788 Fluorescence microscopy was used to locate the carbohydrate epitopes that are associated with the major cell wall polysaccharides and glycoproteins. 36613996 1 32 theme carnivorous 118:128 arg1 plants 130:135 carnivorous plants 118:135 carnivorous plants 118:135 The digestive organs of carnivorous plants have external (abaxial) glands and trichomes, which perform various functions. 36613996 3 33 theme study 359:363 arg1 aim 348:350 The aim 344:350 The aim of the study 344:363 The aim of the study was to fill in the gap regarding the structure of the stellate outer trichomes and their immunocytochemistry and to determine whether these data support the suggestions of other authors about the roles of these trichomes. 36613996 3 34 theme trichomes 576:584 arg1 roles 561:565 the roles 557:565 the roles of these trichomes 557:584 The aim of the study was to fill in the gap regarding the structure of the stellate outer trichomes and their immunocytochemistry and to determine whether these data support the suggestions of other authors about the roles of these trichomes. 36613996 11 35 theme thick 1684:1688 arg1 walls 1695:1699 the thick cell walls 1680:1699 the thick cell walls of the outer head cells 1680:1723 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 9 36 theme trap 1488:1491 arg1 entrance 1493:1500 the trap entrance 1484:1500 the trap entrance 1484:1500 In the immature traps, young stellate trichomes produce mucilage which may protect the trap surface, and in particular, the trap entrance. 36613996 1 37 theme plants 130:135 arg1 organs 108:113 The digestive organs 94:113 The digestive organs of carnivorous plants 94:135 The digestive organs of carnivorous plants have external (abaxial) glands and trichomes, which perform various functions. 36613996 2 38 theme external 324:331 arg1 trichomes 333:341 external trichomes 324:341 external trichomes 324:341 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 7 39 theme cell 1072:1075 arg1 walls 1077:1081 their cell walls 1066:1081 their cell walls 1066:1081 Trichome cells differ in the composition of their cell walls, e.g., the cell walls of the internal head cells are enriched with arabinogalactan proteins (AGPs). 36613996 3 40 theme trichomes 434:442 arg1 structure 402:410 the structure 398:410 the structure of the stellate outer trichomes and their immunocytochemistry 398:472 The aim of the study was to fill in the gap regarding the structure of the stellate outer trichomes and their immunocytochemistry and to determine whether these data support the suggestions of other authors about the roles of these trichomes. 36613996 12 41 theme stellate 1799:1806 arg1 hydathodes 1836:1845 hydathodes 1836:1845 hydathodes 1836:1845 This may suggest that mature stellate trichomes might function as hydathodes, but this should be experimentally proven. 36613996 12 41 theme stellate 1799:1806 arg1 trichomes 1808:1816 mature stellate trichomes 1792:1816 mature stellate trichomes 1792:1816 This may suggest that mature stellate trichomes might function as hydathodes, but this should be experimentally proven. 36613996 1 42 contain have 137:140 arg1 organs 108:113 The digestive organs 94:113 The digestive organs of carnivorous plants 94:135 The digestive organs of carnivorous plants have external (abaxial) glands and trichomes, which perform various functions. 36613996 1 42 contain have 137:140 arg2 trichomes 172:180 trichomes 172:180 trichomes 172:180 The digestive organs of carnivorous plants have external (abaxial) glands and trichomes, which perform various functions. 36613996 1 42 contain have 137:140 arg2 glands 161:166 external (abaxial) glands 142:166 external (abaxial) glands 142:166 The digestive organs of carnivorous plants have external (abaxial) glands and trichomes, which perform various functions. 36613996 2 43 theme Venus 245:249 arg1 flytrap 251:257 the Venus flytrap 241:257 the Venus flytrap 241:257 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 2 43 theme Venus 245:249 arg1 Ellis 234:238 Dionaea muscipula Ellis 216:238 Dionaea muscipula Ellis (the Venus flytrap) 216:258 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 6 44 theme internal 834:841 arg1 cells 903:907 transfer cells 894:907 transfer cells 894:907 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 44 theme internal 834:841 arg1 cells 848:852 internal head cells 834:852 internal head cells 834:852 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 44 theme internal 834:841 arg1 idea 932:935 the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes 928:1019 the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes 928:1019 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 44 theme internal 834:841 arg1 cells 824:828 The endodermal cells 809:828 The endodermal cells 809:828 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 2 45 theme carnivorous 271:281 arg1 Ellis 234:238 Dionaea muscipula Ellis 216:238 Dionaea muscipula Ellis (the Venus flytrap) 216:258 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 2 45 theme carnivorous 271:281 arg1 species 289:295 a model carnivorous plant species 263:295 a model carnivorous plant species whose traps are covered by external trichomes 263:341 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 7 46 theme Trichome 1022:1029 arg1 cells 1031:1035 Trichome cells 1022:1035 Trichome cells 1022:1035 Trichome cells differ in the composition of their cell walls, e.g., the cell walls of the internal head cells are enriched with arabinogalactan proteins (AGPs). 36613996 5 47 theme wall 769:772 arg1 polysaccharides 774:788 the major cell wall polysaccharides 754:788 the major cell wall polysaccharides 754:788 Fluorescence microscopy was used to locate the carbohydrate epitopes that are associated with the major cell wall polysaccharides and glycoproteins. 36613996 11 48 theme cell 1690:1693 arg1 walls 1695:1699 the thick cell walls 1680:1699 the thick cell walls of the outer head cells 1680:1723 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 3 49 theme other 537:541 arg1 authors 543:549 other authors 537:549 other authors 537:549 The aim of the study was to fill in the gap regarding the structure of the stellate outer trichomes and their immunocytochemistry and to determine whether these data support the suggestions of other authors about the roles of these trichomes. 36613996 7 50 theme cells 1126:1130 arg1 walls 1099:1103 the cell walls 1090:1103 the cell walls of the internal head cells 1090:1130 Trichome cells differ in the composition of their cell walls, e.g., the cell walls of the internal head cells are enriched with arabinogalactan proteins (AGPs). 36613996 11 51 theme apoplastic 1752:1761 arg1 space 1763:1767 a large apoplastic space 1744:1767 a large apoplastic space 1744:1767 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 8 52 theme -β-D-galactan 1349:1361 arg1 polysaccharide 1329:1342 the pectic polysaccharide 1318:1342 the pectic polysaccharide (1-4)-β-D-galactan 1318:1361 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 7 53 theme cell 1094:1097 arg1 walls 1099:1103 the cell walls 1090:1103 the cell walls of the internal head cells 1090:1130 Trichome cells differ in the composition of their cell walls, e.g., the cell walls of the internal head cells are enriched with arabinogalactan proteins (AGPs). 36613996 8 54 theme head 1211:1214 arg1 cells 1216:1220 the outer head cells 1201:1220 the outer head cells 1201:1220 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 11 55 theme head 1605:1608 arg1 cells 1610:1614 the internal head cells 1592:1614 the internal head cells 1592:1614 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 7 56 theme arabinogalactan 1150:1164 arg1 AGPs 1176:1179 AGPs 1176:1179 AGPs 1176:1179 Trichome cells differ in the composition of their cell walls, e.g., the cell walls of the internal head cells are enriched with arabinogalactan proteins (AGPs). 36613996 7 56 theme arabinogalactan 1150:1164 arg1 proteins 1166:1173 arabinogalactan proteins 1150:1173 arabinogalactan proteins (AGPs) 1150:1180 Trichome cells differ in the composition of their cell walls, e.g., the cell walls of the internal head cells are enriched with arabinogalactan proteins (AGPs). 36613996 2 57 theme muscipula 224:232 arg1 flytrap 251:257 the Venus flytrap 241:257 the Venus flytrap 241:257 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 2 57 theme muscipula 224:232 arg1 Ellis 234:238 Dionaea muscipula Ellis 216:238 Dionaea muscipula Ellis (the Venus flytrap) 216:258 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 2 57 theme muscipula 224:232 arg1 species 289:295 a model carnivorous plant species 263:295 a model carnivorous plant species whose traps are covered by external trichomes 263:341 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 9 58 dep entrance 1493:1500 arg1 particular 1472:1481 particular 1472:1481 particular 1472:1481 In the immature traps, young stellate trichomes produce mucilage which may protect the trap surface, and in particular, the trap entrance. 36613996 9 59 theme young 1387:1391 arg1 trichomes 1402:1410 young stellate trichomes 1387:1410 young stellate trichomes 1387:1410 In the immature traps, young stellate trichomes produce mucilage which may protect the trap surface, and in particular, the trap entrance. 36613996 8 60 from polysaccharide 1329:1342 arg1 rich 1310:1313 rich 1310:1313 rich 1310:1313 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 60 from polysaccharide 1329:1342 arg1 trichomes 1296:1304 the immature trichomes 1283:1304 the immature trichomes 1283:1304 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 5 61 used used 688:691 arg2 microscopy 673:682 Fluorescence microscopy 660:682 Fluorescence microscopy 660:682 Fluorescence microscopy was used to locate the carbohydrate epitopes that are associated with the major cell wall polysaccharides and glycoproteins. 36613996 6 62 theme stellate 942:949 arg1 trichomes 951:959 stellate trichomes 942:959 stellate trichomes 942:959 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 0 63 from Trichomes 9:17 arg1 Ellis 40:44 Ellis 40:44 Ellis 40:44 Stellate Trichomes in Dionaea muscipula Ellis (Venus Flytrap) Traps, Structure and Functions. 36613996 0 63 from Trichomes 9:17 arg1 Flytrap 53:59 Flytrap 53:59 Flytrap 53:59 Stellate Trichomes in Dionaea muscipula Ellis (Venus Flytrap) Traps, Structure and Functions. 36613996 0 63 from Trichomes 9:17 arg1 Functions 83:91 Functions 83:91 Functions 83:91 Stellate Trichomes in Dionaea muscipula Ellis (Venus Flytrap) Traps, Structure and Functions. 36613996 0 63 from Trichomes 9:17 arg1 Structure 69:77 Structure 69:77 Structure 69:77 Stellate Trichomes in Dionaea muscipula Ellis (Venus Flytrap) Traps, Structure and Functions. 36613996 11 64 theme thick 1619:1623 arg1 cell 1640:1643 a thick secondary wall cell 1617:1643 a thick secondary wall cell 1617:1643 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 5 65 theme Fluorescence 660:671 arg1 microscopy 673:682 Fluorescence microscopy 660:682 Fluorescence microscopy 660:682 Fluorescence microscopy was used to locate the carbohydrate epitopes that are associated with the major cell wall polysaccharides and glycoproteins. 36613996 6 66 dep are 983:985 arg1 only 991:994 only 991:994 only 991:994 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 8 67 theme low 1239:1241 arg1 HGs 1273:1275 HGs 1273:1275 HGs 1273:1275 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 67 theme low 1239:1241 arg1 homogalacturonans 1254:1270 both low and highly homogalacturonans 1234:1270 both low and highly homogalacturonans (HGs) 1234:1276 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 2 68 theme plant 283:287 arg1 Ellis 234:238 Dionaea muscipula Ellis 216:238 Dionaea muscipula Ellis (the Venus flytrap) 216:258 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 2 68 theme plant 283:287 arg1 species 289:295 a model carnivorous plant species 263:295 a model carnivorous plant species whose traps are covered by external trichomes 263:341 Dionaea muscipula Ellis (the Venus flytrap) is a model carnivorous plant species whose traps are covered by external trichomes. 36613996 7 69 theme internal 1112:1119 arg1 cells 1126:1130 the internal head cells 1108:1130 the internal head cells 1108:1130 Trichome cells differ in the composition of their cell walls, e.g., the cell walls of the internal head cells are enriched with arabinogalactan proteins (AGPs). 36613996 9 70 dep immature 1371:1378 arg1 traps 1380:1384 traps 1380:1384 traps 1380:1384 In the immature traps, young stellate trichomes produce mucilage which may protect the trap surface, and in particular, the trap entrance. 36613996 3 71 theme stellate 419:426 arg1 trichomes 434:442 the stellate outer trichomes 415:442 the stellate outer trichomes 415:442 The aim of the study was to fill in the gap regarding the structure of the stellate outer trichomes and their immunocytochemistry and to determine whether these data support the suggestions of other authors about the roles of these trichomes. 36613996 11 72 theme wall 1635:1638 arg1 cell 1640:1643 a thick secondary wall cell 1617:1643 a thick secondary wall cell 1617:1643 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 11 73 theme cells 1719:1723 arg1 walls 1695:1699 the thick cell walls 1680:1699 the thick cell walls of the outer head cells 1680:1723 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 5 74 theme major 758:762 arg1 polysaccharides 774:788 the major cell wall polysaccharides 754:788 the major cell wall polysaccharides 754:788 Fluorescence microscopy was used to locate the carbohydrate epitopes that are associated with the major cell wall polysaccharides and glycoproteins. 36613996 6 75 theme tomentose-like 996:1009 arg1 trichomes 1011:1019 tomentose-like trichomes 996:1019 tomentose-like trichomes 996:1019 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 10 76 theme trichomes 1530:1538 arg1 different 1543:1551 different 1543:1551 different 1543:1551 However, the role of these trichomes is different when the outer head cells collapse. 36613996 10 76 theme trichomes 1530:1538 arg1 role 1516:1519 the role 1512:1519 the role of these trichomes 1512:1538 However, the role of these trichomes is different when the outer head cells collapse. 36613996 6 77 theme endodermal 813:822 arg1 cells 848:852 internal head cells 834:852 internal head cells 834:852 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 77 theme endodermal 813:822 arg1 cells 903:907 transfer cells 894:907 transfer cells 894:907 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 77 theme endodermal 813:822 arg1 idea 932:935 the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes 928:1019 the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes 928:1019 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 6 77 theme endodermal 813:822 arg1 cells 824:828 The endodermal cells 809:828 The endodermal cells 809:828 The endodermal cells and internal head cells of the trichomes were differentiated as transfer cells, and this supports the idea that stellate trichomes transport solutes and are not only tomentose-like trichomes. 36613996 0 78 dep Ellis 40:44 arg1 Traps 62:66 Traps 62:66 Traps 62:66 Stellate Trichomes in Dionaea muscipula Ellis (Venus Flytrap) Traps, Structure and Functions. 36613996 8 79 theme immature 1287:1294 arg1 rich 1310:1313 rich 1310:1313 rich 1310:1313 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 79 theme immature 1287:1294 arg1 trichomes 1296:1304 the immature trichomes 1283:1304 the immature trichomes 1283:1304 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 3 80 theme outer 428:432 arg1 trichomes 434:442 the stellate outer trichomes 415:442 the stellate outer trichomes 415:442 The aim of the study was to fill in the gap regarding the structure of the stellate outer trichomes and their immunocytochemistry and to determine whether these data support the suggestions of other authors about the roles of these trichomes. 36613996 8 81 from homogalacturonans 1254:1270 arg1 poor 1226:1229 poor 1226:1229 poor 1226:1229 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 81 from homogalacturonans 1254:1270 arg1 walls 1192:1196 The cell walls 1183:1196 The cell walls of the outer head cells 1183:1220 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 82 theme highly 1247:1252 arg1 HGs 1273:1275 HGs 1273:1275 HGs 1273:1275 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 8 82 theme highly 1247:1252 arg1 homogalacturonans 1254:1270 both low and highly homogalacturonans 1234:1270 both low and highly homogalacturonans (HGs) 1234:1276 The cell walls of the outer head cells are poor in both low and highly homogalacturonans (HGs), but the immature trichomes are rich in the pectic polysaccharide (1-4)-β-D-galactan. 36613996 11 83 theme outer 1708:1712 arg1 cells 1719:1723 the outer head cells 1704:1723 the outer head cells 1704:1723 In the internal head cells, a thick secondary wall cell was deposited, which together with the thick cell walls of the outer head cells played the role of a large apoplastic space. 36613996 1 84 theme various 197:203 arg1 functions 205:213 various functions 197:213 various functions 197:213 The digestive organs of carnivorous plants have external (abaxial) glands and trichomes, which perform various functions. 36613996 3 85 theme immunocytochemistry 454:472 arg1 structure 402:410 the structure 398:410 the structure of the stellate outer trichomes and their immunocytochemistry 398:472 The aim of the study was to fill in the gap regarding the structure of the stellate outer trichomes and their immunocytochemistry and to determine whether these data support the suggestions of other authors about the roles of these trichomes. 35357812 2 0 theme tau 376:378 arg1 protein 380:386 the microtubule-associated tau protein 349:386 the microtubule-associated tau protein 349:386 In Alzheimer's disease and in rare tauopathies, aggregation of the microtubule-associated tau protein leads to the formation of neurofibrillary tangles (NFT). 35357812 9 1 theme utilized 1661:1668 arg1 model 1711:1715 a frequently utilized α-synuclein-dependent preclinical rodent model 1648:1715 a frequently utilized α-synuclein-dependent preclinical rodent model of PD 1648:1721 In addition, ASN90 slowed the progression of motor impairment and reduced astrogliosis in a frequently utilized α-synuclein-dependent preclinical rodent model of PD. 35357812 4 2 theme glycoside 623:631 arg1 O-GlcNAcase 643:653 the glycoside hydrolase O-GlcNAcase 619:653 the glycoside hydrolase O-GlcNAcase (OGA) 619:659 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 4 2 theme glycoside 623:631 arg1 OGA 656:658 OGA 656:658 OGA 656:658 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 8 3 from survival 1548:1555 arg1 behavior 1510:1517 motor behavior 1504:1517 motor behavior 1504:1517 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 8 3 from survival 1548:1555 arg1 breathing 1523:1531 breathing 1523:1531 breathing 1523:1531 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 3 4 theme intracellular 504:516 arg1 bodies 523:528 intracellular Lewy bodies 504:528 intracellular Lewy bodies containing aggregates of α-synuclein 504:565 In Parkinson's disease (PD) and other α-synucleinopathies, intracellular Lewy bodies containing aggregates of α-synuclein constitute the pathological hallmark. 35357812 9 5 theme preclinical 1692:1702 arg1 model 1711:1715 a frequently utilized α-synuclein-dependent preclinical rodent model 1648:1715 a frequently utilized α-synuclein-dependent preclinical rodent model of PD 1648:1721 In addition, ASN90 slowed the progression of motor impairment and reduced astrogliosis in a frequently utilized α-synuclein-dependent preclinical rodent model of PD. 35357812 4 6 theme O-linked 685:692 arg1 moieties 728:735 O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties 685:735 O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties 685:735 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 1 7 theme toxic 200:204 arg1 aggregates 214:223 insoluble and toxic protein aggregates 186:223 aggregates 214:223 Neurodegenerative proteinopathies are characterized by the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression. 35357812 1 8 theme aggregates 214:223 arg1 formation 173:181 the intracellular formation 155:181 the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression 155:283 Neurodegenerative proteinopathies are characterized by the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression. 35357812 9 9 theme PD 1720:1721 arg1 model 1711:1715 a frequently utilized α-synuclein-dependent preclinical rodent model 1648:1715 a frequently utilized α-synuclein-dependent preclinical rodent model of PD 1648:1721 In addition, ASN90 slowed the progression of motor impairment and reduced astrogliosis in a frequently utilized α-synuclein-dependent preclinical rodent model of PD. 35357812 3 10 theme pathological 582:593 arg1 hallmark 595:602 the pathological hallmark 578:602 the pathological hallmark 578:602 In Parkinson's disease (PD) and other α-synucleinopathies, intracellular Lewy bodies containing aggregates of α-synuclein constitute the pathological hallmark. 35357812 8 11 from development 1435:1445 arg1 behavior 1510:1517 motor behavior 1504:1517 motor behavior 1504:1517 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 8 11 from development 1435:1445 arg1 breathing 1523:1531 breathing 1523:1531 breathing 1523:1531 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 8 12 theme pathology 1454:1462 arg1 development 1435:1445 the development 1431:1445 the development of tau pathology (NFT formation) 1431:1478 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 8 12 theme pathology 1454:1462 arg1 survival 1548:1555 increased survival 1538:1555 increased survival 1538:1555 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 8 12 theme pathology 1454:1462 arg1 formation 1469:1477 NFT formation 1465:1477 NFT formation 1465:1477 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 8 12 theme pathology 1454:1462 arg1 deficits 1492:1499 functional deficits 1481:1499 functional deficits in motor behavior and breathing 1481:1531 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 6 13 theme small 1076:1080 arg1 ASN90 1106:1110 ASN90 1106:1110 ASN90 1106:1110 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 6 13 theme small 1076:1080 arg1 inhibitor 1095:1103 a novel small molecule OGA inhibitor 1068:1103 a novel small molecule OGA inhibitor 1068:1103 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 11 14 theme further 2030:2036 arg1 development 2047:2057 further clinical development 2030:2057 further clinical development 2030:2057 Since tau and α-synuclein pathologies frequently co-exist in neurodegenerative diseases, OGA inhibitors represent unique, multimodal drug candidates for further clinical development. 35357812 8 15 theme NFT 1465:1467 arg1 development 1435:1445 the development 1431:1445 the development of tau pathology (NFT formation) 1431:1478 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 8 15 theme NFT 1465:1467 arg1 formation 1469:1477 NFT formation 1465:1477 NFT formation 1465:1477 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 4 16 link O-linked 685:692 arg1 moieties 728:735 O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties 685:735 O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties 685:735 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 11 17 theme neurodegenerative 1938:1954 arg1 diseases 1956:1963 neurodegenerative diseases 1938:1963 neurodegenerative diseases 1938:1963 Since tau and α-synuclein pathologies frequently co-exist in neurodegenerative diseases, OGA inhibitors represent unique, multimodal drug candidates for further clinical development. 35357812 1 18 attach linked 255:260 arg1 progression 273:283 disease progression 265:283 disease progression 265:283 Neurodegenerative proteinopathies are characterized by the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression. 35357812 1 18 attach linked 255:260 arg2 brain 232:236 the brain 228:236 the brain that are closely linked to disease progression 228:283 Neurodegenerative proteinopathies are characterized by the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression. 35357812 8 19 theme oral 1392:1395 arg1 administration 1397:1410 oral administration 1392:1410 oral administration of ASN90 1392:1419 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 8 20 theme functional 1481:1490 arg1 deficits 1492:1499 functional deficits 1481:1499 functional deficits in motor behavior and breathing 1481:1531 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 7 21 theme transgenic 1314:1323 arg1 mice 1325:1328 transgenic mice 1314:1328 transgenic mice 1314:1328 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 11 22 theme OGA 1966:1968 arg1 inhibitors 1970:1979 OGA inhibitors 1966:1979 OGA inhibitors 1966:1979 Since tau and α-synuclein pathologies frequently co-exist in neurodegenerative diseases, OGA inhibitors represent unique, multimodal drug candidates for further clinical development. 35357812 7 23 theme OGA 1229:1231 arg1 ASN90 1243:1247 the clinical OGA inhibitor ASN90 1216:1247 the clinical OGA inhibitor ASN90 1216:1247 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 1 24 theme insoluble 186:194 arg1 aggregates 214:223 insoluble and toxic protein aggregates 186:223 aggregates 214:223 Neurodegenerative proteinopathies are characterized by the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression. 35357812 8 25 theme tauopathy 1368:1376 arg1 models 1384:1389 human tauopathy mouse models 1362:1389 human tauopathy mouse models 1362:1389 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 2 26 theme neurofibrillary 414:428 arg1 NFT 439:441 NFT 439:441 NFT 439:441 In Alzheimer's disease and in rare tauopathies, aggregation of the microtubule-associated tau protein leads to the formation of neurofibrillary tangles (NFT). 35357812 2 26 theme neurofibrillary 414:428 arg1 tangles 430:436 neurofibrillary tangles 414:436 neurofibrillary tangles (NFT) 414:442 In Alzheimer's disease and in rare tauopathies, aggregation of the microtubule-associated tau protein leads to the formation of neurofibrillary tangles (NFT). 35357812 0 27 theme Multimodal 33:42 arg1 ASN90 22:26 O-GlcNAcase Inhibitor ASN90 0:26 O-GlcNAcase Inhibitor ASN90 0:26 O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies. 35357812 0 27 theme Multimodal 33:42 arg1 Candidate 49:57 a Multimodal Drug Candidate 31:57 a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies 31:97 O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies. 35357812 6 28 theme OGA 1091:1093 arg1 ASN90 1106:1110 ASN90 1106:1110 ASN90 1106:1110 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 6 28 theme OGA 1091:1093 arg1 inhibitor 1095:1103 a novel small molecule OGA inhibitor 1068:1103 a novel small molecule OGA inhibitor 1068:1103 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 6 29 dep discovery 1039:1047 arg1 the 1023:1025 the 1023:1025 the 1023:1025 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 0 30 theme O-GlcNAcase 0:10 arg1 ASN90 22:26 O-GlcNAcase Inhibitor ASN90 0:26 O-GlcNAcase Inhibitor ASN90 0:26 O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies. 35357812 0 30 theme O-GlcNAcase 0:10 arg1 Candidate 49:57 a Multimodal Drug Candidate 31:57 a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies 31:97 O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies. 35357812 7 31 theme daily 1336:1340 arg1 dosing 1347:1352 daily oral dosing 1336:1352 daily oral dosing 1336:1352 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 4 32 theme attractive 787:796 arg1 approach 810:817 an attractive therapeutic approach 784:817 an attractive therapeutic approach to prevent the formation of tau pathology 784:859 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 7 33 theme target 1184:1189 arg1 engagement 1191:1200 target engagement 1184:1200 target engagement in the brain 1184:1213 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 7 34 theme mice 1325:1328 arg1 brains 1304:1309 brains 1304:1309 brains of transgenic mice 1304:1328 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 2 35 theme microtubule-associated 353:374 arg1 protein 380:386 the microtubule-associated tau protein 349:386 the microtubule-associated tau protein 349:386 In Alzheimer's disease and in rare tauopathies, aggregation of the microtubule-associated tau protein leads to the formation of neurofibrillary tangles (NFT). 35357812 0 36 theme Drug 44:47 arg1 ASN90 22:26 O-GlcNAcase Inhibitor ASN90 0:26 O-GlcNAcase Inhibitor ASN90 0:26 O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies. 35357812 0 36 theme Drug 44:47 arg1 Candidate 49:57 a Multimodal Drug Candidate 31:57 a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies 31:97 O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies. 35357812 9 37 theme impairment 1609:1618 arg1 progression 1588:1598 the progression 1584:1598 the progression of motor impairment 1584:1618 In addition, ASN90 slowed the progression of motor impairment and reduced astrogliosis in a frequently utilized α-synuclein-dependent preclinical rodent model of PD. 35357812 11 38 dep unique 1991:1996 arg1 multimodal 1999:2008 multimodal 1999:2008 multimodal 1999:2008 Since tau and α-synuclein pathologies frequently co-exist in neurodegenerative diseases, OGA inhibitors represent unique, multimodal drug candidates for further clinical development. 35357812 7 39 with Consistent 1113:1122 arg1 exposure 1145:1152 the substantial exposure 1129:1152 the substantial exposure of the drug 1129:1164 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 4 40 theme hydrolase 633:641 arg1 O-GlcNAcase 643:653 the glycoside hydrolase O-GlcNAcase 619:653 the glycoside hydrolase O-GlcNAcase (OGA) 619:659 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 4 40 theme hydrolase 633:641 arg1 OGA 656:658 OGA 656:658 OGA 656:658 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 11 41 theme unique 1991:1996 arg1 candidates 2015:2024 unique, multimodal drug candidates 1991:2024 unique, multimodal drug candidates for further clinical development 1991:2057 Since tau and α-synuclein pathologies frequently co-exist in neurodegenerative diseases, OGA inhibitors represent unique, multimodal drug candidates for further clinical development. 35357812 8 42 theme tau 1450:1452 arg1 pathology 1454:1462 tau pathology 1450:1462 tau pathology 1450:1462 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 7 43 theme clinical 1220:1227 arg1 ASN90 1243:1247 the clinical OGA inhibitor ASN90 1216:1247 the clinical OGA inhibitor ASN90 1216:1247 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 7 44 theme substantial 1133:1143 arg1 exposure 1145:1152 the substantial exposure 1129:1152 the substantial exposure of the drug 1129:1164 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 2 45 theme protein 380:386 arg1 aggregation 334:344 aggregation 334:344 aggregation of the microtubule-associated tau protein 334:386 In Alzheimer's disease and in rare tauopathies, aggregation of the microtubule-associated tau protein leads to the formation of neurofibrillary tangles (NFT). 35357812 1 46 theme disease 265:271 arg1 progression 273:283 disease progression 265:283 disease progression 265:283 Neurodegenerative proteinopathies are characterized by the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression. 35357812 3 47 theme α-synuclein 555:565 arg1 aggregates 541:550 aggregates 541:550 aggregates of α-synuclein 541:565 In Parkinson's disease (PD) and other α-synucleinopathies, intracellular Lewy bodies containing aggregates of α-synuclein constitute the pathological hallmark. 35357812 9 48 theme α-synuclein-dependent 1670:1690 arg1 model 1711:1715 a frequently utilized α-synuclein-dependent preclinical rodent model 1648:1715 a frequently utilized α-synuclein-dependent preclinical rodent model of PD 1648:1721 In addition, ASN90 slowed the progression of motor impairment and reduced astrogliosis in a frequently utilized α-synuclein-dependent preclinical rodent model of PD. 35357812 7 49 from O-GlcNAcylation 1262:1276 arg1 brains 1304:1309 brains 1304:1309 brains of transgenic mice 1304:1328 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 11 50 theme α-synuclein 1891:1901 arg1 pathologies 1903:1913 α-synuclein pathologies 1891:1913 α-synuclein pathologies 1891:1913 Since tau and α-synuclein pathologies frequently co-exist in neurodegenerative diseases, OGA inhibitors represent unique, multimodal drug candidates for further clinical development. 35357812 9 51 theme rodent 1704:1709 arg1 model 1711:1715 a frequently utilized α-synuclein-dependent preclinical rodent model 1648:1715 a frequently utilized α-synuclein-dependent preclinical rodent model of PD 1648:1721 In addition, ASN90 slowed the progression of motor impairment and reduced astrogliosis in a frequently utilized α-synuclein-dependent preclinical rodent model of PD. 35357812 10 52 theme disease-modifying 1807:1823 arg1 agents 1825:1830 disease-modifying agents 1807:1830 disease-modifying agents in both tauopathies and α-synucleinopathies 1807:1874 These findings provide a strong rationale for the development of OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies. 35357812 1 53 theme protein 206:212 arg1 aggregates 214:223 insoluble and toxic protein aggregates 186:223 aggregates 214:223 Neurodegenerative proteinopathies are characterized by the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression. 35357812 4 54 theme N-acetyl-d-glucosamine 694:715 arg1 moieties 728:735 O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties 685:735 O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties 685:735 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 2 55 theme rare 316:319 arg1 tauopathies 321:331 rare tauopathies 316:331 rare tauopathies 316:331 In Alzheimer's disease and in rare tauopathies, aggregation of the microtubule-associated tau protein leads to the formation of neurofibrillary tangles (NFT). 35357812 1 56 theme intracellular 159:171 arg1 formation 173:181 the intracellular formation 155:181 the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression 155:283 Neurodegenerative proteinopathies are characterized by the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression. 35357812 11 57 theme drug 2010:2013 arg1 candidates 2015:2024 unique, multimodal drug candidates 1991:2024 unique, multimodal drug candidates for further clinical development 1991:2057 Since tau and α-synuclein pathologies frequently co-exist in neurodegenerative diseases, OGA inhibitors represent unique, multimodal drug candidates for further clinical development. 35357812 4 58 theme intracellular 742:754 arg1 proteins 756:763 intracellular proteins 742:763 intracellular proteins 742:763 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 10 59 theme inhibitors 1793:1802 arg1 development 1774:1784 the development 1770:1784 the development of OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies 1770:1874 These findings provide a strong rationale for the development of OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies. 35357812 7 60 theme inhibitor 1233:1241 arg1 ASN90 1243:1247 the clinical OGA inhibitor ASN90 1216:1247 the clinical OGA inhibitor ASN90 1216:1247 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 11 61 theme clinical 2038:2045 arg1 development 2047:2057 further clinical development 2030:2057 further clinical development 2030:2057 Since tau and α-synuclein pathologies frequently co-exist in neurodegenerative diseases, OGA inhibitors represent unique, multimodal drug candidates for further clinical development. 35357812 5 62 theme O-GlcNAc 913:920 arg1 moieties 922:929 O-GlcNAc moieties 913:929 O-GlcNAc moieties 913:929 Like tau, α-synuclein is known to be modified with O-GlcNAc moieties and in vitro these have been shown to prevent its aggregation and toxicity. 35357812 6 63 theme preclinical 1027:1037 arg1 discovery 1039:1047 preclinical discovery 1027:1047 preclinical discovery 1027:1047 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 8 64 theme motor 1504:1508 arg1 behavior 1510:1517 motor behavior 1504:1517 motor behavior 1504:1517 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 4 65 theme O-GlcNAc 718:725 arg1 moieties 728:735 O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties 685:735 O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties 685:735 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 0 66 theme α-Synuclein 71:81 arg1 Proteinopathies 83:97 α-Synuclein Proteinopathies 71:97 α-Synuclein Proteinopathies 71:97 O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies. 35357812 3 67 contain containing 530:539 arg2 aggregates 541:550 aggregates 541:550 aggregates of α-synuclein 541:565 In Parkinson's disease (PD) and other α-synucleinopathies, intracellular Lewy bodies containing aggregates of α-synuclein constitute the pathological hallmark. 35357812 3 67 contain containing 530:539 arg1 bodies 523:528 intracellular Lewy bodies 504:528 intracellular Lewy bodies containing aggregates of α-synuclein 504:565 In Parkinson's disease (PD) and other α-synucleinopathies, intracellular Lewy bodies containing aggregates of α-synuclein constitute the pathological hallmark. 35357812 4 68 theme moieties 728:735 arg1 removal 674:680 the removal 670:680 the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins 670:763 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 8 69 from deficits 1492:1499 arg1 behavior 1510:1517 motor behavior 1504:1517 motor behavior 1504:1517 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 8 69 from deficits 1492:1499 arg1 breathing 1523:1531 breathing 1523:1531 breathing 1523:1531 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 10 70 theme OGA 1789:1791 arg1 inhibitors 1793:1802 OGA inhibitors 1789:1802 OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies 1789:1874 These findings provide a strong rationale for the development of OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies. 35357812 4 71 theme therapeutic 798:808 arg1 approach 810:817 an attractive therapeutic approach 784:817 an attractive therapeutic approach to prevent the formation of tau pathology 784:859 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 1 72 from formation 173:181 arg1 brain 232:236 the brain 228:236 the brain that are closely linked to disease progression 228:283 Neurodegenerative proteinopathies are characterized by the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression. 35357812 10 73 from agents 1825:1830 arg1 α-synucleinopathies 1856:1874 α-synucleinopathies 1856:1874 α-synucleinopathies 1856:1874 These findings provide a strong rationale for the development of OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies. 35357812 10 73 from agents 1825:1830 arg1 tauopathies 1840:1850 tauopathies 1840:1850 tauopathies 1840:1850 These findings provide a strong rationale for the development of OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies. 35357812 7 74 theme oral 1342:1345 arg1 dosing 1347:1352 daily oral dosing 1336:1352 daily oral dosing 1336:1352 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 7 75 from engagement 1191:1200 arg1 brain 1209:1213 the brain 1205:1213 the brain 1205:1213 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 8 76 theme human 1362:1366 arg1 models 1384:1389 human tauopathy mouse models 1362:1389 human tauopathy mouse models 1362:1389 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 0 77 theme Inhibitor 12:20 arg1 ASN90 22:26 O-GlcNAcase Inhibitor ASN90 0:26 O-GlcNAcase Inhibitor ASN90 0:26 O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies. 35357812 0 77 theme Inhibitor 12:20 arg1 Candidate 49:57 a Multimodal Drug Candidate 31:57 a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies 31:97 O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies. 35357812 6 78 theme molecule 1082:1089 arg1 ASN90 1106:1110 ASN90 1106:1110 ASN90 1106:1110 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 6 78 theme molecule 1082:1089 arg1 inhibitor 1095:1103 a novel small molecule OGA inhibitor 1068:1103 a novel small molecule OGA inhibitor 1068:1103 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 8 79 theme mouse 1378:1382 arg1 models 1384:1389 human tauopathy mouse models 1362:1389 human tauopathy mouse models 1362:1389 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 4 80 theme tau 847:849 arg1 pathology 851:859 tau pathology 847:859 tau pathology 847:859 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 1 81 theme Neurodegenerative 100:116 arg1 proteinopathies 118:132 Neurodegenerative proteinopathies 100:132 Neurodegenerative proteinopathies 100:132 Neurodegenerative proteinopathies are characterized by the intracellular formation of insoluble and toxic protein aggregates in the brain that are closely linked to disease progression. 35357812 6 82 theme novel 1070:1074 arg1 ASN90 1106:1110 ASN90 1106:1110 ASN90 1106:1110 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 6 82 theme novel 1070:1074 arg1 inhibitor 1095:1103 a novel small molecule OGA inhibitor 1068:1103 a novel small molecule OGA inhibitor 1068:1103 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 7 83 theme drug 1161:1164 arg1 exposure 1145:1152 the substantial exposure 1129:1152 the substantial exposure of the drug 1129:1164 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 6 84 theme inhibitor 1095:1103 arg1 development 1053:1063 development 1053:1063 development 1053:1063 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 6 84 theme inhibitor 1095:1103 arg1 discovery 1039:1047 preclinical discovery 1027:1047 preclinical discovery 1027:1047 Here, we report the preclinical discovery and development of a novel small molecule OGA inhibitor, ASN90. 35357812 4 85 theme pathology 851:859 arg1 formation 834:842 the formation 830:842 the formation of tau pathology 830:859 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 2 86 theme tangles 430:436 arg1 formation 401:409 the formation 397:409 the formation of neurofibrillary tangles (NFT) 397:442 In Alzheimer's disease and in rare tauopathies, aggregation of the microtubule-associated tau protein leads to the formation of neurofibrillary tangles (NFT). 35357812 9 87 theme motor 1603:1607 arg1 impairment 1609:1618 motor impairment 1603:1618 motor impairment 1603:1618 In addition, ASN90 slowed the progression of motor impairment and reduced astrogliosis in a frequently utilized α-synuclein-dependent preclinical rodent model of PD. 35357812 8 88 theme increased 1538:1546 arg1 survival 1548:1555 increased survival 1538:1555 increased survival 1538:1555 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 7 89 theme α-synuclein 1289:1299 arg1 O-GlcNAcylation 1262:1276 the O-GlcNAcylation 1258:1276 the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice 1258:1328 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 8 90 theme ASN90 1415:1419 arg1 administration 1397:1410 oral administration 1392:1410 oral administration of ASN90 1392:1419 Across human tauopathy mouse models, oral administration of ASN90 prevented the development of tau pathology (NFT formation), functional deficits in motor behavior and breathing, and increased survival. 35357812 3 91 theme Lewy 518:521 arg1 bodies 523:528 intracellular Lewy bodies 504:528 intracellular Lewy bodies containing aggregates of α-synuclein 504:565 In Parkinson's disease (PD) and other α-synucleinopathies, intracellular Lewy bodies containing aggregates of α-synuclein constitute the pathological hallmark. 35357812 7 92 theme tau 1281:1283 arg1 O-GlcNAcylation 1262:1276 the O-GlcNAcylation 1258:1276 the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice 1258:1328 Consistent with the substantial exposure of the drug and demonstrating target engagement in the brain, the clinical OGA inhibitor ASN90 promoted the O-GlcNAcylation of tau and α-synuclein in brains of transgenic mice after daily oral dosing. 35357812 4 93 theme O-GlcNAcase 643:653 arg1 Inhibition 605:614 Inhibition 605:614 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) 605:659 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 3 94 theme other 477:481 arg1 α-synucleinopathies 483:501 other α-synucleinopathies 477:501 other α-synucleinopathies 477:501 In Parkinson's disease (PD) and other α-synucleinopathies, intracellular Lewy bodies containing aggregates of α-synuclein constitute the pathological hallmark. 35357812 4 95 from proteins 756:763 arg1 removal 674:680 the removal 670:680 the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins 670:763 Inhibition of the glycoside hydrolase O-GlcNAcase (OGA) prevents the removal of O-linked N-acetyl-d-glucosamine (O-GlcNAc) moieties from intracellular proteins and has emerged as an attractive therapeutic approach to prevent the formation of tau pathology. 35357812 5 96 mod modified 899:906 arg3 moieties 922:929 O-GlcNAc moieties 913:929 O-GlcNAc moieties 913:929 Like tau, α-synuclein is known to be modified with O-GlcNAc moieties and in vitro these have been shown to prevent its aggregation and toxicity. 35357812 5 96 mod modified 899:906 arg1 α-synuclein 872:882 α-synuclein 872:882 α-synuclein 872:882 Like tau, α-synuclein is known to be modified with O-GlcNAc moieties and in vitro these have been shown to prevent its aggregation and toxicity. 35357812 10 97 theme strong 1749:1754 arg1 rationale 1756:1764 a strong rationale 1747:1764 a strong rationale for the development of OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies 1747:1874 These findings provide a strong rationale for the development of OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies. 34986481 6 0 from Levels 846:851 arg1 cells 958:962 cells 958:962 cells 958:962 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 2 1 theme -induced 330:337 arg1 damage 358:363 high glucose (HG)-induced spermatogenic cell damage 313:363 high glucose (HG)-induced spermatogenic cell damage 313:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 8 2 theme luciferase 1064:1073 arg1 assay 1084:1088 dual luciferase reporter assay 1059:1088 dual luciferase reporter assay 1059:1088 Besides, dual luciferase reporter assay was employed to verify the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1). 34986481 4 3 theme apoptosis-related 595:611 arg1 proteins 613:620 apoptosis-related proteins 595:620 apoptosis-related proteins 595:620 And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. 34986481 13 4 theme new 1791:1793 arg1 strategy 1805:1812 a new treatment strategy 1789:1812 a new treatment strategy for the treatment of DM-induced testicular damage 1789:1862 CONCLUSION miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. 34986481 7 5 theme Cell 992:995 arg1 apoptosis 997:1005 Cell apoptosis 992:1005 Cell apoptosis 992:1005 Cell apoptosis was determined using flow cytometry assay. 34986481 11 6 theme biosynthetic 1522:1533 arg1 HBP 1544:1546 HBP 1544:1546 HBP 1544:1546 miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. 34986481 11 6 theme biosynthetic 1522:1533 arg1 pathway 1535:1541 hexosamine biosynthetic pathway 1511:1541 hexosamine biosynthetic pathway (HBP) signaling 1511:1557 miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. 34986481 3 7 dep assay 537:541 arg1 5-diphenyltetrazolium 501:521 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay 466:541 5-diphenyltetrazolium 501:521 METHODS GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. 34986481 3 8 theme MTT 532:534 arg1 assay 537:541 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay 466:541 assay 537:541 METHODS GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. 34986481 1 9 theme spermatogenic 207:219 arg1 cells 221:225 spermatogenic cells 207:225 spermatogenic cells 207:225 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. 34986481 3 10 theme bromide 523:529 arg1 assay 537:541 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay 466:541 assay 537:541 METHODS GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. 34986481 13 11 theme spermatogenic 1717:1729 arg1 damage 1736:1741 HG-induced spermatogenic cell damage 1706:1741 HG-induced spermatogenic cell damage 1706:1741 CONCLUSION miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. 34986481 8 12 theme binding 1117:1123 arg1 relationship 1125:1136 the binding relationship 1113:1136 the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) 1113:1213 Besides, dual luciferase reporter assay was employed to verify the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1). 34986481 6 13 theme species 872:878 arg1 activity 916:923 activity 916:923 activity of superoxide dismutase (SOD) in cells 916:962 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 6 13 theme species 872:878 arg1 Levels 846:851 Levels 846:851 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) 846:910 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 6 14 theme reactive 856:863 arg1 species 872:878 reactive oxygen species 856:878 reactive oxygen species (ROS) 856:884 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 6 14 theme reactive 856:863 arg1 dialdehyde 895:904 malonic dialdehyde 887:904 malonic dialdehyde (MDA) 887:910 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 6 14 theme reactive 856:863 arg1 ROS 881:883 ROS 881:883 ROS 881:883 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 2 15 theme molecular 265:273 arg1 mechanism 275:283 the molecular mechanism 261:283 the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage 261:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 1 16 theme testicular 147:156 arg1 damage 158:163 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage 103:163 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage 103:163 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. 34986481 4 17 theme autophagy-related 627:643 arg1 proteins 645:652 autophagy-related proteins 627:652 autophagy-related proteins 627:652 And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. 34986481 5 18 theme factor-α 714:721 arg1 Levels 689:694 Levels 689:694 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) 689:784 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 5 19 theme UDP-N-acetylglucosamine 749:771 arg1 Levels 689:694 Levels 689:694 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) 689:784 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 2 20 from -27b-3p 302:308 arg1 damage 358:363 high glucose (HG)-induced spermatogenic cell damage 313:363 high glucose (HG)-induced spermatogenic cell damage 313:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 6 21 from activity 916:923 arg1 cells 958:962 cells 958:962 cells 958:962 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 11 22 from activation 1497:1506 arg1 cells 1587:1591 HG-treated spermatogenic cells 1562:1591 HG-treated spermatogenic cells 1562:1591 miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. 34986481 5 23 theme tumor 699:703 arg1 factor-α 714:721 tumor necrosis factor-α 699:721 tumor necrosis factor-α (TNF-α) 699:729 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 5 23 theme tumor 699:703 arg1 TNF-α 724:728 TNF-α 724:728 TNF-α 724:728 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 5 24 link linked 810:815 arg1 ELISA 832:836 ELISA 832:836 ELISA 832:836 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 5 24 link linked 810:815 arg1 assay 839:843 enzyme linked immunosorbent (ELISA) assay 803:843 enzyme linked immunosorbent (ELISA) assay 803:843 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 2 25 from roles 251:255 arg1 damage 358:363 high glucose (HG)-induced spermatogenic cell damage 313:363 high glucose (HG)-induced spermatogenic cell damage 313:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 3 26 theme GC-1 374:377 arg1 cells 383:387 GC-1 spg cells 374:387 GC-1 spg cells 374:387 METHODS GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. 34986481 0 27 theme Gfpt1/HBP 82:90 arg1 Signaling 92:100 Gfpt1/HBP Signaling 82:100 Gfpt1/HBP Signaling 82:100 miR-27b-3p Improved High Glucose-Induced Spermatogenic Cell Damage via Regulating Gfpt1/HBP Signaling. 34986481 1 28 theme Diabetes 116:123 arg1 DM 135:136 DM 135:136 DM 135:136 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. 34986481 1 28 theme Diabetes 116:123 arg1 mellitus 125:132 INTRODUCTION Diabetes mellitus 103:132 INTRODUCTION Diabetes mellitus (DM) 103:137 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. 34986481 3 29 theme Cell 435:438 arg1 viability 440:448 24 h. Cell viability 429:448 24 h. Cell viability 429:448 METHODS GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. 34986481 0 30 theme High 20:23 arg1 Damage 60:65 High Glucose-Induced Spermatogenic Cell Damage 20:65 High Glucose-Induced Spermatogenic Cell Damage 20:65 miR-27b-3p Improved High Glucose-Induced Spermatogenic Cell Damage via Regulating Gfpt1/HBP Signaling. 34986481 9 31 theme GC-1 1276:1279 arg1 cells 1285:1289 HG-treated GC-1 spg cells 1265:1289 HG-treated GC-1 spg cells 1265:1289 RESULTS miR-27b-3p was markedly downregulated in HG-treated GC-1 spg cells. 34986481 4 32 link O-linked 559:566 arg1 OGT 589:591 OGT 589:591 OGT 589:591 And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. 34986481 4 32 link O-linked 559:566 arg1 N-acetylglucosamine 568:586 O-linked N-acetylglucosamine 559:586 O-linked N-acetylglucosamine (OGT) 559:592 And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. 34986481 2 33 from mechanism 275:283 arg1 damage 358:363 high glucose (HG)-induced spermatogenic cell damage 313:363 high glucose (HG)-induced spermatogenic cell damage 313:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 13 34 theme testicular 1846:1855 arg1 damage 1857:1862 DM-induced testicular damage 1835:1862 DM-induced testicular damage 1835:1862 CONCLUSION miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. 34986481 0 35 theme Spermatogenic 41:53 arg1 Damage 60:65 High Glucose-Induced Spermatogenic Cell Damage 20:65 High Glucose-Induced Spermatogenic Cell Damage 20:65 miR-27b-3p Improved High Glucose-Induced Spermatogenic Cell Damage via Regulating Gfpt1/HBP Signaling. 34986481 6 36 theme dismutase 939:947 arg1 activity 916:923 activity 916:923 activity of superoxide dismutase (SOD) in cells 916:962 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 6 36 theme dismutase 939:947 arg1 Levels 846:851 Levels 846:851 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) 846:910 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 11 37 theme signaling 1549:1557 arg1 activation 1497:1506 the activation 1493:1506 the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells 1493:1591 miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. 34986481 7 38 theme cytometry 1033:1041 arg1 assay 1043:1047 flow cytometry assay 1028:1047 flow cytometry assay 1028:1047 Cell apoptosis was determined using flow cytometry assay. 34986481 10 39 theme miR-27b-3p 1444:1453 arg1 overexpression 1455:1468 miR-27b-3p overexpression 1444:1468 miR-27b-3p overexpression 1444:1468 HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. 34986481 13 40 theme treatment 1795:1803 arg1 strategy 1805:1812 a new treatment strategy 1789:1812 a new treatment strategy for the treatment of DM-induced testicular damage 1789:1862 CONCLUSION miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. 34986481 10 41 theme HG 1292:1293 arg1 treatment 1295:1303 HG treatment 1292:1303 HG treatment 1292:1303 HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. 34986481 5 42 theme IL-1β 732:736 arg1 Levels 689:694 Levels 689:694 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) 689:784 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 11 43 theme HG-treated 1562:1571 arg1 cells 1587:1591 HG-treated spermatogenic cells 1562:1591 HG-treated spermatogenic cells 1562:1591 miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. 34986481 2 44 theme spermatogenic 339:351 arg1 damage 358:363 high glucose (HG)-induced spermatogenic cell damage 313:363 high glucose (HG)-induced spermatogenic cell damage 313:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 10 45 dep caused 1305:1310 arg1 increased 1338:1346 increased 1338:1346 increased oxidative stress and inflammation 1338:1380 HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. 34986481 10 45 dep caused 1305:1310 arg1 decreased 1312:1320 decreased 1312:1320 decreased cell viability 1312:1335 HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. 34986481 10 45 dep caused 1305:1310 arg1 induced 1387:1393 induced 1387:1393 induced autophagy and apoptosis 1387:1417 HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. 34986481 13 46 theme CONCLUSION 1670:1679 arg1 miR-27b-3p 1681:1690 CONCLUSION miR-27b-3p 1670:1690 CONCLUSION miR-27b-3p 1670:1690 CONCLUSION miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. 34986481 11 47 theme pathway 1535:1541 arg1 signaling 1549:1557 hexosamine biosynthetic pathway (HBP) signaling 1511:1557 hexosamine biosynthetic pathway (HBP) signaling 1511:1557 miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. 34986481 10 48 theme cell 1322:1325 arg1 viability 1327:1335 cell viability 1322:1335 cell viability 1322:1335 HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. 34986481 2 49 theme miR 298:300 arg1 -27b-3p 302:308 microRNA (miR)-27b-3p 288:308 microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage 288:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 2 50 theme microRNA 288:295 arg1 -27b-3p 302:308 microRNA (miR)-27b-3p 288:308 microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage 288:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 1 51 theme abnormal 185:192 arg1 apoptosis 194:202 abnormal apoptosis 185:202 abnormal apoptosis of spermatogenic cells 185:225 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. 34986481 8 52 theme dual 1059:1062 arg1 assay 1084:1088 dual luciferase reporter assay 1059:1088 dual luciferase reporter assay 1059:1088 Besides, dual luciferase reporter assay was employed to verify the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1). 34986481 10 53 theme oxidative 1348:1356 arg1 stress 1358:1363 oxidative stress 1348:1363 oxidative stress 1348:1363 HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. 34986481 2 54 theme high 313:316 arg1 HG 327:328 HG 327:328 HG 327:328 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 2 54 theme high 313:316 arg1 glucose 318:324 high glucose 313:324 high glucose (HG)-induced spermatogenic cell damage 313:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 8 55 theme reporter 1075:1082 arg1 assay 1084:1088 dual luciferase reporter assay 1059:1088 dual luciferase reporter assay 1059:1088 Besides, dual luciferase reporter assay was employed to verify the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1). 34986481 6 56 theme malonic 887:893 arg1 MDA 907:909 MDA 907:909 MDA 907:909 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 6 56 theme malonic 887:893 arg1 species 872:878 reactive oxygen species 856:878 reactive oxygen species (ROS) 856:884 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 6 56 theme malonic 887:893 arg1 dialdehyde 895:904 malonic dialdehyde 887:904 malonic dialdehyde (MDA) 887:910 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 2 57 from damage 358:363 arg1 roles 251:255 the roles 247:255 the roles 247:255 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 2 57 from damage 358:363 arg1 mechanism 275:283 the molecular mechanism 261:283 the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage 261:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 4 58 theme proteins 613:620 arg1 levels 549:554 levels 549:554 levels 549:554 And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. 34986481 13 59 theme Gfpt1/HBP 1758:1766 arg1 signaling 1768:1776 Gfpt1/HBP signaling 1758:1776 Gfpt1/HBP signaling 1758:1776 CONCLUSION miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. 34986481 11 60 theme hexosamine 1511:1520 arg1 HBP 1544:1546 HBP 1544:1546 HBP 1544:1546 miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. 34986481 11 60 theme hexosamine 1511:1520 arg1 pathway 1535:1541 hexosamine biosynthetic pathway 1511:1541 hexosamine biosynthetic pathway (HBP) signaling 1511:1557 miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. 34986481 2 61 theme -27b-3p 302:308 arg1 roles 251:255 the roles 247:255 the roles 247:255 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 2 61 theme -27b-3p 302:308 arg1 mechanism 275:283 the molecular mechanism 261:283 the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage 261:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 1 62 theme cells 221:225 arg1 apoptosis 194:202 abnormal apoptosis 185:202 abnormal apoptosis of spermatogenic cells 185:225 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. 34986481 8 63 theme glutamine-fructose-6-phosphate 1161:1190 arg1 transaminase 1192:1203 glutamine-fructose-6-phosphate transaminase 1 1161:1205 glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) 1161:1213 Besides, dual luciferase reporter assay was employed to verify the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1). 34986481 8 63 theme glutamine-fructose-6-phosphate 1161:1190 arg1 Gfpt1 1208:1212 Gfpt1 1208:1212 Gfpt1 1208:1212 Besides, dual luciferase reporter assay was employed to verify the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1). 34986481 13 64 theme HG-induced 1706:1715 arg1 damage 1736:1741 HG-induced spermatogenic cell damage 1706:1741 HG-induced spermatogenic cell damage 1706:1741 CONCLUSION miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. 34986481 5 65 theme linked 810:815 arg1 ELISA 832:836 ELISA 832:836 ELISA 832:836 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 5 65 theme linked 810:815 arg1 assay 839:843 enzyme linked immunosorbent (ELISA) assay 803:843 enzyme linked immunosorbent (ELISA) assay 803:843 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 13 66 theme cell 1731:1734 arg1 damage 1736:1741 HG-induced spermatogenic cell damage 1706:1741 HG-induced spermatogenic cell damage 1706:1741 CONCLUSION miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. 34986481 6 67 theme oxygen 865:870 arg1 species 872:878 reactive oxygen species 856:878 reactive oxygen species (ROS) 856:884 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 6 67 theme oxygen 865:870 arg1 dialdehyde 895:904 malonic dialdehyde 887:904 malonic dialdehyde (MDA) 887:910 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 6 67 theme oxygen 865:870 arg1 ROS 881:883 ROS 881:883 ROS 881:883 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 1 68 theme -induced 138:145 arg1 damage 158:163 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage 103:163 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage 103:163 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. 34986481 6 69 theme superoxide 928:937 arg1 SOD 950:952 SOD 950:952 SOD 950:952 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 6 69 theme superoxide 928:937 arg1 dismutase 939:947 superoxide dismutase 928:947 superoxide dismutase (SOD) 928:953 Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. 34986481 4 70 theme Western 675:681 arg1 blot 683:686 Western blot 675:686 Western blot 675:686 And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. 34986481 5 71 theme necrosis 705:712 arg1 factor-α 714:721 tumor necrosis factor-α 699:721 tumor necrosis factor-α (TNF-α) 699:729 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 5 71 theme necrosis 705:712 arg1 TNF-α 724:728 TNF-α 724:728 TNF-α 724:728 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 5 72 theme immunosorbent 817:829 arg1 ELISA 832:836 ELISA 832:836 ELISA 832:836 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 5 72 theme immunosorbent 817:829 arg1 assay 839:843 enzyme linked immunosorbent (ELISA) assay 803:843 enzyme linked immunosorbent (ELISA) assay 803:843 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 3 73 dep METHODS 366:372 arg1 treated 394:400 treated 394:400 were treated with 30 mmol/L glucose for 24 h. Cell viability 389:448 METHODS GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. 34986481 4 74 theme proteins 645:652 arg1 levels 549:554 levels 549:554 levels 549:554 And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. 34986481 9 75 theme RESULTS 1216:1222 arg1 miR-27b-3p 1224:1233 RESULTS miR-27b-3p 1216:1233 RESULTS miR-27b-3p 1216:1233 RESULTS miR-27b-3p was markedly downregulated in HG-treated GC-1 spg cells. 34986481 13 76 theme damage 1857:1862 arg1 treatment 1822:1830 the treatment 1818:1830 the treatment of DM-induced testicular damage 1818:1862 CONCLUSION miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. 34986481 4 77 theme N-acetylglucosamine 568:586 arg1 levels 549:554 levels 549:554 levels 549:554 And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. 34986481 5 78 theme IL-6 739:742 arg1 Levels 689:694 Levels 689:694 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) 689:784 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 1 79 theme INTRODUCTION 103:114 arg1 DM 135:136 DM 135:136 DM 135:136 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. 34986481 1 79 theme INTRODUCTION 103:114 arg1 mellitus 125:132 INTRODUCTION Diabetes mellitus 103:132 INTRODUCTION Diabetes mellitus (DM) 103:137 INTRODUCTION Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. 34986481 3 80 theme spg 379:381 arg1 cells 383:387 GC-1 spg cells 374:387 GC-1 spg cells 374:387 METHODS GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. 34986481 3 81 theme mmol/L 410:415 arg1 glucose 417:423 30 mmol/L glucose 407:423 30 mmol/L glucose 407:423 METHODS GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. 34986481 0 82 theme Glucose-Induced 25:39 arg1 Damage 60:65 High Glucose-Induced Spermatogenic Cell Damage 20:65 High Glucose-Induced Spermatogenic Cell Damage 20:65 miR-27b-3p Improved High Glucose-Induced Spermatogenic Cell Damage via Regulating Gfpt1/HBP Signaling. 34986481 9 83 theme HG-treated 1265:1274 arg1 cells 1285:1289 HG-treated GC-1 spg cells 1265:1289 HG-treated GC-1 spg cells 1265:1289 RESULTS miR-27b-3p was markedly downregulated in HG-treated GC-1 spg cells. 34986481 13 84 theme DM-induced 1835:1844 arg1 damage 1857:1862 DM-induced testicular damage 1835:1862 DM-induced testicular damage 1835:1862 CONCLUSION miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. 34986481 0 85 theme Cell 55:58 arg1 Damage 60:65 High Glucose-Induced Spermatogenic Cell Damage 20:65 High Glucose-Induced Spermatogenic Cell Damage 20:65 miR-27b-3p Improved High Glucose-Induced Spermatogenic Cell Damage via Regulating Gfpt1/HBP Signaling. 34986481 9 86 theme spg 1281:1283 arg1 cells 1285:1289 HG-treated GC-1 spg cells 1265:1289 HG-treated GC-1 spg cells 1265:1289 RESULTS miR-27b-3p was markedly downregulated in HG-treated GC-1 spg cells. 34986481 5 87 dep linked 810:815 arg1 enzyme 803:808 enzyme 803:808 enzyme 803:808 Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. 34986481 3 88 theme h. 432:433 arg1 viability 440:448 24 h. Cell viability 429:448 24 h. Cell viability 429:448 METHODS GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. 34986481 7 89 theme flow 1028:1031 arg1 assay 1043:1047 flow cytometry assay 1028:1047 flow cytometry assay 1028:1047 Cell apoptosis was determined using flow cytometry assay. 34986481 11 90 theme spermatogenic 1573:1585 arg1 cells 1587:1591 HG-treated spermatogenic cells 1562:1591 HG-treated spermatogenic cells 1562:1591 miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. 34986481 2 91 theme glucose 318:324 arg1 damage 358:363 high glucose (HG)-induced spermatogenic cell damage 313:363 high glucose (HG)-induced spermatogenic cell damage 313:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34986481 4 92 theme O-linked 559:566 arg1 OGT 589:591 OGT 589:591 OGT 589:591 And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. 34986481 4 92 theme O-linked 559:566 arg1 N-acetylglucosamine 568:586 O-linked N-acetylglucosamine 559:586 O-linked N-acetylglucosamine (OGT) 559:592 And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. 34986481 2 93 theme cell 353:356 arg1 damage 358:363 high glucose (HG)-induced spermatogenic cell damage 313:363 high glucose (HG)-induced spermatogenic cell damage 313:363 Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. 34469899 8 0 theme multivariate 1171:1182 arg1 analysis 1184:1191 multivariate analysis 1171:1191 multivariate analysis 1171:1191 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 6 1 dep r=0.308 1003:1009 arg1 P=0.017 1012:1018 P=0.017 1012:1018 P=0.017 1012:1018 A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). 34469899 9 2 theme OGA 1503:1505 arg1 P=0.019 1512:1518 P=0.019 1512:1518 P=0.019 1512:1518 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 2 theme OGA 1503:1505 arg1 IRS 1507:1509 lower OGA IRS 1497:1509 lower OGA IRS (P=0.019) 1497:1519 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 10 3 theme independent 1620:1630 arg1 predictor 1632:1640 the only independent predictor 1611:1640 the only independent predictor for short metastasis-free survival (P=0.006) 1611:1685 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 10 3 theme independent 1620:1630 arg1 IRS 1603:1605 lower OGA IRS 1593:1605 lower OGA IRS 1593:1605 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 10 4 theme short 1646:1650 arg1 P=0.006 1678:1684 P=0.006 1678:1684 P=0.006 1678:1684 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 10 4 theme short 1646:1650 arg1 survival 1668:1675 short metastasis-free survival 1646:1675 short metastasis-free survival (P=0.006) 1646:1685 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 12 5 used used 1849:1852 arg2 indicator 1875:1883 a poor prognostic indicator 1857:1883 a poor prognostic indicator 1857:1883 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 12 5 used used 1849:1852 arg2 level 1818:1822 Low level 1814:1822 Low level of OGA expression 1814:1840 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 7 6 theme chemotherapeutic-responder 1121:1146 arg1 patients 1148:1155 poor chemotherapeutic-responder patients 1116:1155 poor chemotherapeutic-responder patients (P=0.001) 1116:1165 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 7 6 theme chemotherapeutic-responder 1121:1146 arg1 P=0.001 1158:1164 P=0.001 1158:1164 P=0.001 1158:1164 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 9 7 theme Subgroup 1321:1328 arg1 analysis 1330:1337 Subgroup analysis 1321:1337 Subgroup analysis in stage IIB osteosarcoma (n=70) 1321:1370 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 10 8 theme lower 1593:1597 arg1 predictor 1632:1640 the only independent predictor 1611:1640 the only independent predictor for short metastasis-free survival (P=0.006) 1611:1685 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 10 8 theme lower 1593:1597 arg1 IRS 1603:1605 lower OGA IRS 1593:1605 lower OGA IRS 1593:1605 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 9 9 theme tumor 1422:1426 arg1 P=0.026 1440:1446 P=0.026 1440:1446 P=0.026 1440:1446 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 9 theme tumor 1422:1426 arg1 recurrence 1428:1437 tumor recurrence 1422:1437 tumor recurrence (P=0.026) 1422:1447 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 5 10 theme metastasis-free 847:861 arg1 survival 863:870 metastasis-free survival 847:870 metastasis-free survival 847:870 Correlations between the immunoreactive score (IRS) and clinicopathologic parameters, overall survival, and metastasis-free survival were evaluated. 34469899 4 11 theme diagnosed 654:662 arg1 patients 677:684 109 first diagnosed osteosarcoma patients 644:684 109 first diagnosed osteosarcoma patients 644:684 There were 109 first diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). 34469899 4 11 theme diagnosed 654:662 arg1 IIB 712:714 Enneking stage IIB 697:714 Enneking stage IIB (n=70) 697:721 There were 109 first diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). 34469899 2 12 theme osteosarcoma 293:304 arg1 pathogenesis 277:288 the pathogenesis 273:288 the pathogenesis of osteosarcoma 273:304 However, its implication in the pathogenesis of osteosarcoma remains unclear. 34469899 10 13 theme only 1615:1618 arg1 predictor 1632:1640 the only independent predictor 1611:1640 the only independent predictor for short metastasis-free survival (P=0.006) 1611:1685 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 10 13 theme only 1615:1618 arg1 IRS 1603:1605 lower OGA IRS 1593:1605 lower OGA IRS 1593:1605 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 4 14 theme Enneking 697:704 arg1 n=70 717:720 n=70 717:720 n=70 717:720 There were 109 first diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). 34469899 4 14 theme Enneking 697:704 arg1 IIB 712:714 Enneking stage IIB 697:714 Enneking stage IIB (n=70) 697:721 There were 109 first diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). 34469899 3 15 theme O-GlcNAc 369:376 arg1 levels 359:364 the levels 355:364 the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) 355:468 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 7 16 theme poor 1116:1119 arg1 patients 1148:1155 poor chemotherapeutic-responder patients 1116:1155 poor chemotherapeutic-responder patients (P=0.001) 1116:1165 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 7 16 theme poor 1116:1119 arg1 P=0.001 1158:1164 P=0.001 1158:1164 P=0.001 1158:1164 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 1 17 theme Several 89:95 arg1 studies 97:103 Several studies 89:103 Several studies 89:103 Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modification of tumor-associated proteins. 34469899 1 18 theme various 180:186 arg1 carcinomas 188:197 various carcinomas 180:197 various carcinomas 180:197 Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modification of tumor-associated proteins. 34469899 3 19 theme O-linked 401:408 arg1 OGT 443:445 OGT 443:445 OGT 443:445 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 3 19 theme O-linked 401:408 arg1 transferase 430:440 O-linked N-acetylglucosamine transferase 401:440 O-linked N-acetylglucosamine transferase (OGT) 401:446 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 9 20 theme stage 1342:1346 arg1 n=70 1366:1369 n=70 1366:1369 n=70 1366:1369 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 20 theme stage 1342:1346 arg1 osteosarcoma 1352:1363 stage IIB osteosarcoma 1342:1363 stage IIB osteosarcoma (n=70) 1342:1370 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 12 21 theme prognostic 1864:1873 arg1 level 1818:1822 Low level 1814:1822 Low level of OGA expression 1814:1840 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 12 21 theme prognostic 1864:1873 arg1 indicator 1875:1883 a poor prognostic indicator 1857:1883 a poor prognostic indicator 1857:1883 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 1 22 theme carcinomas 188:197 arg1 tumorigenesis 163:175 tumorigenesis 163:175 tumorigenesis of various carcinomas 163:197 Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modification of tumor-associated proteins. 34469899 3 23 theme N-acetylglucosamine 410:428 arg1 OGT 443:445 OGT 443:445 OGT 443:445 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 3 23 theme N-acetylglucosamine 410:428 arg1 transferase 430:440 O-linked N-acetylglucosamine transferase 401:440 O-linked N-acetylglucosamine transferase (OGT) 401:446 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 9 24 theme IIB 1348:1350 arg1 n=70 1366:1369 n=70 1366:1369 n=70 1366:1369 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 24 theme IIB 1348:1350 arg1 osteosarcoma 1352:1363 stage IIB osteosarcoma 1342:1363 stage IIB osteosarcoma (n=70) 1342:1370 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 12 25 theme poor 1859:1862 arg1 level 1818:1822 Low level 1814:1822 Low level of OGA expression 1814:1840 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 12 25 theme poor 1859:1862 arg1 indicator 1875:1883 a poor prognostic indicator 1857:1883 a poor prognostic indicator 1857:1883 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 1 26 from role 125:128 arg1 tumorigenesis 163:175 tumorigenesis 163:175 tumorigenesis of various carcinomas 163:197 Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modification of tumor-associated proteins. 34469899 3 27 theme O-GlcNAcase 452:462 arg1 O-GlcNAc 369:376 O-GlcNAc 369:376 O-GlcNAc 369:376 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 3 27 theme O-GlcNAcase 452:462 arg1 expressions 386:396 the expressions 382:396 the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) 382:468 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 3 28 theme expressions 386:396 arg1 levels 359:364 the levels 355:364 the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) 355:468 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 5 29 theme overall 825:831 arg1 survival 833:840 overall survival 825:840 overall survival 825:840 Correlations between the immunoreactive score (IRS) and clinicopathologic parameters, overall survival, and metastasis-free survival were evaluated. 34469899 5 30 theme clinicopathologic 795:811 arg1 parameters 813:822 clinicopathologic parameters 795:822 clinicopathologic parameters 795:822 Correlations between the immunoreactive score (IRS) and clinicopathologic parameters, overall survival, and metastasis-free survival were evaluated. 34469899 2 31 from implication 258:268 arg1 pathogenesis 277:288 the pathogenesis 273:288 the pathogenesis of osteosarcoma 273:304 However, its implication in the pathogenesis of osteosarcoma remains unclear. 34469899 3 32 theme human 473:477 arg1 tissues 492:498 human osteosarcoma tissues 473:498 human osteosarcoma tissues 473:498 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 0 33 theme O-GlcNAcase 21:31 arg1 Expression 33:42 Expression 33:42 Expression 33:42 Relationship Between O-GlcNAcase Expression and Prognosis of Patients With Osteosarcoma. 34469899 6 34 theme tumor 987:991 arg1 r=0.308 1003:1009 r=0.308 1003:1009 r=0.308 1003:1009 A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). 34469899 6 34 theme tumor 987:991 arg1 necrosis 993:1000 postchemotherapeutic tumor necrosis 966:1000 postchemotherapeutic tumor necrosis (r=0.308; P=0.017) 966:1019 A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). 34469899 12 35 theme expression 1831:1840 arg1 level 1818:1822 Low level 1814:1822 Low level of OGA expression 1814:1840 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 12 35 theme expression 1831:1840 arg1 indicator 1875:1883 a poor prognostic indicator 1857:1883 a poor prognostic indicator 1857:1883 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 6 36 theme positive 890:897 arg1 correlation 899:909 A positive correlation 888:909 A positive correlation 888:909 A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). 34469899 9 37 theme short 1556:1560 arg1 survival 1578:1585 short metastasis-free survival 1556:1585 short metastasis-free survival 1556:1585 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 3 38 theme osteosarcoma 479:490 arg1 tissues 492:498 human osteosarcoma tissues 473:498 human osteosarcoma tissues 473:498 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 6 39 theme postchemotherapeutic 966:985 arg1 r=0.308 1003:1009 r=0.308 1003:1009 r=0.308 1003:1009 A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). 34469899 6 39 theme postchemotherapeutic 966:985 arg1 necrosis 993:1000 postchemotherapeutic tumor necrosis 966:1000 postchemotherapeutic tumor necrosis (r=0.308; P=0.017) 966:1019 A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). 34469899 10 40 theme metastasis-free 1652:1666 arg1 P=0.006 1678:1684 P=0.006 1678:1684 P=0.006 1678:1684 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 10 40 theme metastasis-free 1652:1666 arg1 survival 1668:1675 short metastasis-free survival 1646:1675 short metastasis-free survival (P=0.006) 1646:1685 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 9 41 theme chemotherapeutic 1455:1470 arg1 P=0.022 1483:1489 P=0.022 1483:1489 P=0.022 1483:1489 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 41 theme chemotherapeutic 1455:1470 arg1 responder 1472:1480 poor chemotherapeutic responder 1450:1480 poor chemotherapeutic responder (P=0.022) 1450:1490 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 42 theme metastasis-free 1562:1576 arg1 survival 1578:1585 short metastasis-free survival 1556:1585 short metastasis-free survival 1556:1585 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 4 43 theme stage 706:710 arg1 n=70 717:720 n=70 717:720 n=70 717:720 There were 109 first diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). 34469899 4 43 theme stage 706:710 arg1 IIB 712:714 Enneking stage IIB 697:714 Enneking stage IIB (n=70) 697:721 There were 109 first diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). 34469899 1 44 theme tumor-associated 218:233 arg1 proteins 235:242 tumor-associated proteins 218:242 tumor-associated proteins 218:242 Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modification of tumor-associated proteins. 34469899 9 45 theme recurrence 1428:1437 arg1 P=0.019 1400:1406 P=0.019 1400:1406 P=0.019 1400:1406 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 45 theme recurrence 1428:1437 arg1 IRS 1507:1509 lower OGA IRS 1497:1509 lower OGA IRS (P=0.019) 1497:1519 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 45 theme recurrence 1428:1437 arg1 P=0.022 1483:1489 P=0.022 1483:1489 P=0.022 1483:1489 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 45 theme recurrence 1428:1437 arg1 presence 1410:1417 presence 1410:1417 presence of tumor recurrence (P=0.026) 1410:1447 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 45 theme recurrence 1428:1437 arg1 P=0.019 1512:1518 P=0.019 1512:1518 P=0.019 1512:1518 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 45 theme recurrence 1428:1437 arg1 sex 1395:1397 male sex 1390:1397 male sex (P=0.019) 1390:1407 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 45 theme recurrence 1428:1437 arg1 responder 1472:1480 poor chemotherapeutic responder 1450:1480 poor chemotherapeutic responder (P=0.022) 1450:1490 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 11 46 theme osteosarcoma 1800:1811 arg1 pathogenesis 1765:1776 pathogenesis 1765:1776 pathogenesis 1765:1776 Our findings suggested that O-GlcNAc pathway, especially OGA, may involve in pathogenesis and aggressiveness of osteosarcoma. 34469899 11 46 theme osteosarcoma 1800:1811 arg1 aggressiveness 1782:1795 aggressiveness 1782:1795 aggressiveness 1782:1795 Our findings suggested that O-GlcNAc pathway, especially OGA, may involve in pathogenesis and aggressiveness of osteosarcoma. 34469899 7 47 theme metastatic 1082:1091 arg1 P=0.020 1103:1109 P=0.020 1103:1109 P=0.020 1103:1109 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 7 47 theme metastatic 1082:1091 arg1 patients 1093:1100 metastatic patients 1082:1100 metastatic patients (P=0.020) 1082:1110 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 1 48 theme proteins 235:242 arg1 modification 202:213 modification 202:213 modification of tumor-associated proteins 202:242 Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modification of tumor-associated proteins. 34469899 3 49 theme transferase 430:440 arg1 O-GlcNAc 369:376 O-GlcNAc 369:376 O-GlcNAc 369:376 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 3 49 theme transferase 430:440 arg1 expressions 386:396 the expressions 382:396 the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) 382:468 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 7 50 theme OGA 1071:1073 arg1 IRS 1075:1077 significantly lower OGA IRS 1051:1077 significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001) 1051:1165 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 6 51 theme necrosis 993:1000 arg1 percentage 952:961 the percentage 948:961 the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017) 948:1019 A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). 34469899 6 51 theme necrosis 993:1000 arg1 IRS 933:935 the IRS 929:935 the IRS of OGA 929:942 A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). 34469899 3 52 theme several 595:601 arg1 parameters 621:630 several clinicopathologic parameters 595:630 several clinicopathologic parameters 595:630 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 8 53 theme overall 1303:1309 arg1 survival 1311:1318 shorter overall survival 1295:1318 shorter overall survival 1295:1318 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 8 54 theme lower 1237:1241 arg1 P=0.004 1252:1258 P=0.004 1252:1258 P=0.004 1252:1258 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 8 54 theme lower 1237:1241 arg1 IRS 1247:1249 lower OGA IRS 1237:1249 lower OGA IRS (P=0.004) 1237:1259 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 12 55 theme Low 1814:1816 arg1 level 1818:1822 Low level 1814:1822 Low level of OGA expression 1814:1840 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 12 55 theme Low 1814:1816 arg1 indicator 1875:1883 a poor prognostic indicator 1857:1883 a poor prognostic indicator 1857:1883 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 3 56 theme clinicopathologic 603:619 arg1 parameters 621:630 several clinicopathologic parameters 595:630 several clinicopathologic parameters 595:630 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 9 57 theme poor 1450:1453 arg1 P=0.022 1483:1489 P=0.022 1483:1489 P=0.022 1483:1489 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 57 theme poor 1450:1453 arg1 responder 1472:1480 poor chemotherapeutic responder 1450:1480 poor chemotherapeutic responder (P=0.022) 1450:1490 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 8 58 theme shorter 1295:1301 arg1 survival 1311:1318 shorter overall survival 1295:1318 shorter overall survival 1295:1318 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 9 59 theme male 1390:1393 arg1 P=0.019 1400:1406 P=0.019 1400:1406 P=0.019 1400:1406 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 59 theme male 1390:1393 arg1 sex 1395:1397 male sex 1390:1397 male sex (P=0.019) 1390:1407 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 12 60 theme OGA 1827:1829 arg1 expression 1831:1840 OGA expression 1827:1840 OGA expression 1827:1840 Low level of OGA expression may be used as a poor prognostic indicator. 34469899 7 61 theme Univariate 1022:1031 arg1 analysis 1033:1040 Univariate analysis 1022:1040 Univariate analysis 1022:1040 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 1 62 theme O-GlcNAcylation 133:147 arg1 role 125:128 a role 123:128 a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas 123:197 Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modification of tumor-associated proteins. 34469899 7 63 theme lower 1065:1069 arg1 IRS 1075:1077 significantly lower OGA IRS 1051:1077 significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001) 1051:1165 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 8 64 theme tumor 1206:1210 arg1 P=0.002 1224:1230 P=0.002 1224:1230 P=0.002 1224:1230 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 8 64 theme tumor 1206:1210 arg1 metastasis 1212:1221 tumor metastasis 1206:1221 tumor metastasis (P=0.002) 1206:1231 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 0 65 with Patients 61:68 arg1 Osteosarcoma 75:86 Osteosarcoma 75:86 Osteosarcoma 75:86 Relationship Between O-GlcNAcase Expression and Prognosis of Patients With Osteosarcoma. 34469899 9 66 theme lower 1497:1501 arg1 P=0.019 1512:1518 P=0.019 1512:1518 P=0.019 1512:1518 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 66 theme lower 1497:1501 arg1 IRS 1507:1509 lower OGA IRS 1497:1509 lower OGA IRS (P=0.019) 1497:1519 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 8 67 theme OGA 1243:1245 arg1 P=0.004 1252:1258 P=0.004 1252:1258 P=0.004 1252:1258 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 8 67 theme OGA 1243:1245 arg1 IRS 1247:1249 lower OGA IRS 1237:1249 lower OGA IRS (P=0.004) 1237:1259 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 5 68 theme immunoreactive 764:777 arg1 score 779:783 the immunoreactive score 760:783 the immunoreactive score (IRS) 760:789 Correlations between the immunoreactive score (IRS) and clinicopathologic parameters, overall survival, and metastasis-free survival were evaluated. 34469899 5 68 theme immunoreactive 764:777 arg1 IRS 786:788 IRS 786:788 IRS 786:788 Correlations between the immunoreactive score (IRS) and clinicopathologic parameters, overall survival, and metastasis-free survival were evaluated. 34469899 11 69 theme O-GlcNAc 1716:1723 arg1 pathway 1725:1731 O-GlcNAc pathway 1716:1731 O-GlcNAc pathway 1716:1731 Our findings suggested that O-GlcNAc pathway, especially OGA, may involve in pathogenesis and aggressiveness of osteosarcoma. 34469899 11 69 theme O-GlcNAc 1716:1723 arg1 OGA 1745:1747 OGA 1745:1747 especially OGA 1734:1747 Our findings suggested that O-GlcNAc pathway, especially OGA, may involve in pathogenesis and aggressiveness of osteosarcoma. 34469899 3 70 link O-linked 401:408 arg1 OGT 443:445 OGT 443:445 OGT 443:445 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 3 70 link O-linked 401:408 arg1 transferase 430:440 O-linked N-acetylglucosamine transferase 401:440 O-linked N-acetylglucosamine transferase (OGT) 401:446 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 4 71 theme osteosarcoma 664:675 arg1 patients 677:684 109 first diagnosed osteosarcoma patients 644:684 109 first diagnosed osteosarcoma patients 644:684 There were 109 first diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). 34469899 4 71 theme osteosarcoma 664:675 arg1 IIB 712:714 Enneking stage IIB 697:714 Enneking stage IIB (n=70) 697:721 There were 109 first diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). 34469899 3 72 dep levels 569:574 arg1 the 565:567 the 565:567 the 565:567 This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. 34469899 8 73 theme IRS 1247:1249 arg1 presence 1194:1201 presence 1194:1201 presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) 1194:1259 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 0 74 theme Patients 61:68 arg1 Prognosis 48:56 Prognosis 48:56 Prognosis 48:56 Relationship Between O-GlcNAcase Expression and Prognosis of Patients With Osteosarcoma. 34469899 0 74 theme Patients 61:68 arg1 Expression 33:42 Expression 33:42 Expression 33:42 Relationship Between O-GlcNAcase Expression and Prognosis of Patients With Osteosarcoma. 34469899 6 75 theme OGA 940:942 arg1 percentage 952:961 the percentage 948:961 the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017) 948:1019 A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). 34469899 6 75 theme OGA 940:942 arg1 IRS 933:935 the IRS 929:935 the IRS of OGA 929:942 A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). 34469899 9 76 from analysis 1330:1337 arg1 n=70 1366:1369 n=70 1366:1369 n=70 1366:1369 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 9 76 from analysis 1330:1337 arg1 osteosarcoma 1352:1363 stage IIB osteosarcoma 1342:1363 stage IIB osteosarcoma (n=70) 1342:1370 Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. 34469899 8 77 theme metastasis 1212:1221 arg1 presence 1194:1201 presence 1194:1201 presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) 1194:1259 By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. 34469899 10 78 theme OGA 1599:1601 arg1 predictor 1632:1640 the only independent predictor 1611:1640 the only independent predictor for short metastasis-free survival (P=0.006) 1611:1685 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 10 78 theme OGA 1599:1601 arg1 IRS 1603:1605 lower OGA IRS 1593:1605 lower OGA IRS 1593:1605 But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). 34469899 7 79 from IRS 1075:1077 arg1 patients 1148:1155 poor chemotherapeutic-responder patients 1116:1155 poor chemotherapeutic-responder patients (P=0.001) 1116:1165 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 7 79 from IRS 1075:1077 arg1 P=0.020 1103:1109 P=0.020 1103:1109 P=0.020 1103:1109 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 7 79 from IRS 1075:1077 arg1 patients 1093:1100 metastatic patients 1082:1100 metastatic patients (P=0.020) 1082:1110 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 34469899 7 79 from IRS 1075:1077 arg1 P=0.001 1158:1164 P=0.001 1158:1164 P=0.001 1158:1164 Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). 37334838 0 0 theme stem 97:100 arg1 cell 102:105 pluripotent stem cell 85:105 pluripotent stem cell self-renewal 85:118 An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. 37334838 0 1 theme pluripotent 85:95 arg1 cell 102:105 pluripotent stem cell 85:105 pluripotent stem cell self-renewal 85:118 An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. 37334838 4 2 theme O-GlcNAcylation 687:701 arg1 levels 669:674 decreased levels 659:674 decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP) 659:812 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 0 3 theme self-renewal 107:118 arg1 cell 102:105 pluripotent stem cell 85:105 pluripotent stem cell self-renewal 85:118 An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. 37334838 5 4 theme syndrome 1010:1017 arg1 aetiology 992:1000 the developmental aetiology 974:1000 the developmental aetiology of this syndrome 974:1017 These data establish a link between OGT-CDG and embryonic stem cell self-renewal, providing a foundation for examining the developmental aetiology of this syndrome. 37334838 1 5 theme O-linked 121:128 arg1 enzyme 197:202 an essential enzyme 184:202 an essential enzyme that modifies proteins with O-GlcNAc 184:239 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 1 5 theme O-linked 121:128 arg1 OGT 176:178 OGT 176:178 OGT 176:178 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 1 5 theme O-linked 121:128 arg1 transferase 163:173 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 121:173 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 121:179 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 5 6 theme self-renewal 923:934 arg1 stem 913:916 OGT-CDG and embryonic stem 891:916 OGT-CDG and embryonic stem cell self-renewal 891:934 These data establish a link between OGT-CDG and embryonic stem cell self-renewal, providing a foundation for examining the developmental aetiology of this syndrome. 37334838 3 7 theme OGTC921Y 475:482 arg1 variant 484:490 an OGTC921Y variant 472:490 an OGTC921Y variant that co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity 472:585 Here, we report an OGTC921Y variant that co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity. 37334838 4 8 theme reduced 824:830 arg1 capacity 845:852 reduced self-renewal capacity 824:852 reduced self-renewal capacity 824:852 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 4 9 theme Sox2 764:767 arg1 levels 728:733 decreased levels 718:733 decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP) 718:812 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 2 10 theme X-linked 391:398 arg1 disability 413:422 X-linked intellectual disability 391:422 X-linked intellectual disability (XLID) 391:429 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 2 10 theme X-linked 391:398 arg1 XLID 425:428 XLID 425:428 XLID 425:428 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 5 11 theme OGT-CDG 891:897 arg1 stem 913:916 OGT-CDG and embryonic stem 891:916 OGT-CDG and embryonic stem cell self-renewal 891:934 These data establish a link between OGT-CDG and embryonic stem cell self-renewal, providing a foundation for examining the developmental aetiology of this syndrome. 37334838 3 12 theme epileptic 525:533 arg1 seizures 535:542 epileptic seizures 525:542 epileptic seizures 525:542 Here, we report an OGTC921Y variant that co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity. 37334838 0 13 theme O-GlcNAc 3:10 arg1 transferase 12:22 An O-GlcNAc transferase 0:22 An O-GlcNAc transferase pathogenic variant linked to intellectual disability 0:75 An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. 37334838 0 14 attach linked 43:48 arg1 disability 66:75 intellectual disability 53:75 intellectual disability 53:75 An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. 37334838 0 14 attach linked 43:48 arg2 variant 35:41 An O-GlcNAc transferase pathogenic variant 0:41 An O-GlcNAc transferase pathogenic variant linked to intellectual disability 0:75 An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. 37334838 2 15 theme congenital 317:326 arg1 disorder 328:335 congenital disorder 317:335 congenital disorder of glycosylation (OGT-CDG) 317:362 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 1 16 theme essential 187:195 arg1 enzyme 197:202 an essential enzyme 184:202 an essential enzyme that modifies proteins with O-GlcNAc 184:239 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 1 16 theme essential 187:195 arg1 transferase 163:173 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 121:173 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 121:179 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 2 17 theme developmental 435:447 arg1 delay 449:453 developmental delay 435:453 developmental delay 435:453 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 4 18 theme self-renewal 832:843 arg1 capacity 845:852 reduced self-renewal capacity 824:852 reduced self-renewal capacity 824:852 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 4 19 theme Oct4 738:741 arg1 levels 728:733 decreased levels 718:733 decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP) 718:812 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 4 20 theme decreased 659:667 arg1 levels 669:674 decreased levels 659:674 decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP) 659:812 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 0 21 theme pathogenic 24:33 arg1 variant 35:41 An O-GlcNAc transferase pathogenic variant 0:41 An O-GlcNAc transferase pathogenic variant linked to intellectual disability 0:75 An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. 37334838 3 22 theme activity 578:585 arg1 loss 560:563 loss 560:563 loss of catalytic activity 560:585 Here, we report an OGTC921Y variant that co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity. 37334838 4 23 theme stem 623:626 arg1 cells 628:632 mouse embryonic stem cells 607:632 mouse embryonic stem cells carrying OGTC921Y 607:650 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 0 24 theme transferase 12:22 arg1 variant 35:41 An O-GlcNAc transferase pathogenic variant 0:41 An O-GlcNAc transferase pathogenic variant linked to intellectual disability 0:75 An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. 37334838 2 25 theme novel 303:307 arg1 type 309:312 a novel type 301:312 a novel type 301:312 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 4 26 theme embryonic 613:621 arg1 cells 628:632 mouse embryonic stem cells 607:632 mouse embryonic stem cells carrying OGTC921Y 607:650 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 5 27 theme embryonic 903:911 arg1 stem 913:916 OGT-CDG and embryonic stem 891:916 OGT-CDG and embryonic stem cell self-renewal 891:934 These data establish a link between OGT-CDG and embryonic stem cell self-renewal, providing a foundation for examining the developmental aetiology of this syndrome. 37334838 4 28 contain carrying 634:641 arg1 cells 628:632 mouse embryonic stem cells 607:632 mouse embryonic stem cells carrying OGTC921Y 607:650 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 4 28 contain carrying 634:641 arg2 OGTC921Y 643:650 OGTC921Y 643:650 OGTC921Y 643:650 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 2 29 theme OGT 249:251 arg1 variants 261:268 Inborn OGT genetic variants 242:268 Inborn OGT genetic variants 242:268 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 2 30 link X-linked 391:398 arg1 disability 413:422 X-linked intellectual disability 391:422 X-linked intellectual disability (XLID) 391:429 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 2 30 link X-linked 391:398 arg1 XLID 425:428 XLID 425:428 XLID 425:428 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 2 31 theme Inborn 242:247 arg1 variants 261:268 Inborn OGT genetic variants 242:268 Inborn OGT genetic variants 242:268 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 2 32 theme intellectual 400:411 arg1 disability 413:422 X-linked intellectual disability 391:422 X-linked intellectual disability (XLID) 391:429 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 2 32 theme intellectual 400:411 arg1 XLID 425:428 XLID 425:428 XLID 425:428 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 0 33 theme intellectual 53:64 arg1 disability 66:75 intellectual disability 53:75 intellectual disability 53:75 An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. 37334838 1 34 theme β-N-acetylglucosamine 130:150 arg1 enzyme 197:202 an essential enzyme 184:202 an essential enzyme that modifies proteins with O-GlcNAc 184:239 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 1 34 theme β-N-acetylglucosamine 130:150 arg1 OGT 176:178 OGT 176:178 OGT 176:178 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 1 34 theme β-N-acetylglucosamine 130:150 arg1 transferase 163:173 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 121:173 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 121:179 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 3 35 theme catalytic 568:576 arg1 activity 578:585 catalytic activity 568:585 catalytic activity 568:585 Here, we report an OGTC921Y variant that co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity. 37334838 2 36 theme glycosylation 340:352 arg1 disorder 328:335 congenital disorder 317:335 congenital disorder of glycosylation (OGT-CDG) 317:362 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 4 37 theme alkaline 787:794 arg1 ALP 809:811 ALP 809:811 ALP 809:811 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 4 37 theme alkaline 787:794 arg1 phosphatase 796:806 extracellular alkaline phosphatase 773:806 extracellular alkaline phosphatase (ALP) 773:812 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 4 38 theme decreased 718:726 arg1 levels 728:733 decreased levels 718:733 decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP) 718:812 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 5 39 theme developmental 978:990 arg1 aetiology 992:1000 the developmental aetiology 974:1000 the developmental aetiology of this syndrome 974:1017 These data establish a link between OGT-CDG and embryonic stem cell self-renewal, providing a foundation for examining the developmental aetiology of this syndrome. 37334838 4 40 theme extracellular 773:785 arg1 ALP 809:811 ALP 809:811 ALP 809:811 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 4 40 theme extracellular 773:785 arg1 phosphatase 796:806 extracellular alkaline phosphatase 773:806 extracellular alkaline phosphatase (ALP) 773:812 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 1 41 theme O-GlcNAc 153:160 arg1 enzyme 197:202 an essential enzyme 184:202 an essential enzyme that modifies proteins with O-GlcNAc 184:239 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 1 41 theme O-GlcNAc 153:160 arg1 OGT 176:178 OGT 176:178 OGT 176:178 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 1 41 theme O-GlcNAc 153:160 arg1 transferase 163:173 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 121:173 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 121:179 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 2 42 theme disorder 328:335 arg1 type 309:312 a novel type 301:312 a novel type 301:312 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 37334838 4 43 theme phosphatase 796:806 arg1 levels 728:733 decreased levels 718:733 decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP) 718:812 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 4 44 theme protein 679:685 arg1 O-GlcNAcylation 687:701 protein O-GlcNAcylation 679:701 protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP) 679:812 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 4 45 theme mouse 607:611 arg1 cells 628:632 mouse embryonic stem cells 607:632 mouse embryonic stem cells carrying OGTC921Y 607:650 Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. 37334838 1 46 link O-linked 121:128 arg1 enzyme 197:202 an essential enzyme 184:202 an essential enzyme that modifies proteins with O-GlcNAc 184:239 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 1 46 link O-linked 121:128 arg1 OGT 176:178 OGT 176:178 OGT 176:178 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 1 46 link O-linked 121:128 arg1 transferase 163:173 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 121:173 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 121:179 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. 37334838 2 47 theme genetic 253:259 arg1 variants 261:268 Inborn OGT genetic variants 242:268 Inborn OGT genetic variants 242:268 Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. 36943877 8 0 theme T 1206:1206 arg1 cell-mediated immunity 1208:1229 T cell-mediated immunity 1206:1229 T cell-mediated immunity against tumor cells 1206:1249 We also designed a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells. 36943877 4 1 theme PD-L1 467:471 arg1 degradation 452:462 lysosomal degradation 442:462 lysosomal degradation of PD-L1 442:471 Here, we show that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc) during the intracellular trafficking pathway. 36943877 7 2 theme inhibition 1008:1017 arg1 Combination 984:994 Combination 984:994 Combination of O-GlcNAc inhibition with PD-L1 antibody 984:1037 Combination of O-GlcNAc inhibition with PD-L1 antibody synergistically promotes antitumor immune response. 36943877 2 3 theme PD-L1 342:346 arg1 efficacy 285:292 the efficacy 281:292 the efficacy of immune checkpoint blockade therapy targeting PD-L1 281:346 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 9 4 theme PD-L1-mediated 1372:1385 arg1 therapy 1414:1420 PD-L1-mediated immune checkpoint blockade therapy 1372:1420 PD-L1-mediated immune checkpoint blockade therapy 1372:1420 Collectively, our study reveals a link between O-GlcNAc and tumor immune evasion, and suggests strategies for improving PD-L1-mediated immune checkpoint blockade therapy. 36943877 5 5 theme intracellular 764:776 arg1 PD-L1 778:782 intracellular PD-L1 764:782 intracellular PD-L1 764:782 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 8 6 theme competitive 1110:1120 arg1 inhibitor 1130:1138 a competitive peptide inhibitor 1108:1138 a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells 1108:1249 We also designed a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells. 36943877 2 7 theme targeting 332:340 arg1 PD-L1 342:346 immune checkpoint blockade therapy targeting PD-L1 297:346 immune checkpoint blockade therapy targeting PD-L1 297:346 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 4 8 theme trafficking 554:564 arg1 pathway 566:572 the intracellular trafficking pathway 536:572 the intracellular trafficking pathway 536:572 Here, we show that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc) during the intracellular trafficking pathway. 36943877 6 9 theme immune-competent 918:933 arg1 mice 935:938 immune-competent mice 918:938 immune-competent mice 918:938 O-GlcNAc inhibition activates T cell-mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. 36943877 4 10 theme lysosomal 442:450 arg1 degradation 452:462 lysosomal degradation 442:462 lysosomal degradation of PD-L1 442:471 Here, we show that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc) during the intracellular trafficking pathway. 36943877 5 11 theme hepatocyte 597:606 arg1 component 671:679 a key component 665:679 a key component of the endosomal sorting machinery 665:714 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 11 theme hepatocyte 597:606 arg1 HGS 659:661 HGS 659:661 HGS 659:661 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 11 theme hepatocyte 597:606 arg1 substrate 648:656 the hepatocyte growth factor-regulated tyrosine kinase substrate 593:656 the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) 593:662 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 2 12 theme key 262:264 arg1 determinant 266:276 a key determinant 260:276 a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1 260:346 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 2 12 theme key 262:264 arg1 abundance 225:233 The abundance 221:233 The abundance of cell surface PD-L1 221:255 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 2 13 theme immune 297:302 arg1 PD-L1 342:346 immune checkpoint blockade therapy targeting PD-L1 297:346 immune checkpoint blockade therapy targeting PD-L1 297:346 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 9 14 theme immune 1387:1392 arg1 therapy 1414:1420 PD-L1-mediated immune checkpoint blockade therapy 1372:1420 PD-L1-mediated immune checkpoint blockade therapy 1372:1420 Collectively, our study reveals a link between O-GlcNAc and tumor immune evasion, and suggests strategies for improving PD-L1-mediated immune checkpoint blockade therapy. 36943877 5 15 theme factor-regulated 615:630 arg1 component 671:679 a key component 665:679 a key component of the endosomal sorting machinery 665:714 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 15 theme factor-regulated 615:630 arg1 HGS 659:661 HGS 659:661 HGS 659:661 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 15 theme factor-regulated 615:630 arg1 substrate 648:656 the hepatocyte growth factor-regulated tyrosine kinase substrate 593:656 the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) 593:662 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 16 theme growth 608:613 arg1 component 671:679 a key component 665:679 a key component of the endosomal sorting machinery 665:714 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 16 theme growth 608:613 arg1 HGS 659:661 HGS 659:661 HGS 659:661 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 16 theme growth 608:613 arg1 substrate 648:656 the hepatocyte growth factor-regulated tyrosine kinase substrate 593:656 the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) 593:662 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 8 17 theme tumor 1239:1243 arg1 cells 1245:1249 tumor cells 1239:1249 tumor cells 1239:1249 We also designed a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells. 36943877 9 18 theme checkpoint 1394:1403 arg1 therapy 1414:1420 PD-L1-mediated immune checkpoint blockade therapy 1372:1420 PD-L1-mediated immune checkpoint blockade therapy 1372:1420 Collectively, our study reveals a link between O-GlcNAc and tumor immune evasion, and suggests strategies for improving PD-L1-mediated immune checkpoint blockade therapy. 36943877 5 19 theme tyrosine 632:639 arg1 component 671:679 a key component 665:679 a key component of the endosomal sorting machinery 665:714 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 19 theme tyrosine 632:639 arg1 HGS 659:661 HGS 659:661 HGS 659:661 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 19 theme tyrosine 632:639 arg1 substrate 648:656 the hepatocyte growth factor-regulated tyrosine kinase substrate 593:656 the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) 593:662 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 1 20 theme Programmed-death 89:104 arg1 ligand 106:111 Programmed-death ligand 1 89:113 Programmed-death ligand 1 (PD-L1) 89:121 Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. 36943877 1 20 theme Programmed-death 89:104 arg1 PD-L1 116:120 PD-L1 116:120 PD-L1 116:120 Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. 36943877 8 21 theme HGS 1143:1145 arg1 glycosylation 1147:1159 HGS glycosylation 1143:1159 HGS glycosylation 1143:1159 We also designed a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells. 36943877 7 22 with Combination 984:994 arg1 antibody 1030:1037 PD-L1 antibody 1024:1037 PD-L1 antibody 1024:1037 Combination of O-GlcNAc inhibition with PD-L1 antibody synergistically promotes antitumor immune response. 36943877 5 23 theme impaired 796:803 arg1 degradation 815:825 impaired lysosomal degradation 796:825 impaired lysosomal degradation of PD-L1 796:834 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 4 24 link O-linked 489:496 arg1 O-GlcNAc 519:526 O-GlcNAc 519:526 O-GlcNAc 519:526 Here, we show that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc) during the intracellular trafficking pathway. 36943877 4 24 link O-linked 489:496 arg1 N-acetylglucosamine 498:516 O-linked N-acetylglucosamine 489:516 O-linked N-acetylglucosamine (O-GlcNAc) 489:527 Here, we show that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc) during the intracellular trafficking pathway. 36943877 5 25 theme kinase 641:646 arg1 component 671:679 a key component 665:679 a key component of the endosomal sorting machinery 665:714 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 25 theme kinase 641:646 arg1 HGS 659:661 HGS 659:661 HGS 659:661 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 25 theme kinase 641:646 arg1 substrate 648:656 the hepatocyte growth factor-regulated tyrosine kinase substrate 593:656 the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) 593:662 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 8 26 theme glycosylation 1147:1159 arg1 inhibitor 1130:1138 a competitive peptide inhibitor 1108:1138 a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells 1108:1249 We also designed a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells. 36943877 5 27 theme lysosomal 805:813 arg1 degradation 815:825 impaired lysosomal degradation 796:825 impaired lysosomal degradation of PD-L1 796:834 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 2 28 theme efficacy 285:292 arg1 determinant 266:276 a key determinant 260:276 a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1 260:346 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 2 28 theme efficacy 285:292 arg1 abundance 225:233 The abundance 221:233 The abundance of cell surface PD-L1 221:255 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 0 29 theme immune 31:36 arg1 evasion 38:44 tumor immune evasion 25:44 tumor immune evasion 25:44 O-GlcNAcylation promotes tumor immune evasion by inhibiting PD-L1 lysosomal degradation. 36943877 5 30 theme PD-L1 830:834 arg1 degradation 815:825 impaired lysosomal degradation 796:825 impaired lysosomal degradation of PD-L1 796:834 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 0 31 theme tumor 25:29 arg1 evasion 38:44 tumor immune evasion 25:44 tumor immune evasion 25:44 O-GlcNAcylation promotes tumor immune evasion by inhibiting PD-L1 lysosomal degradation. 36943877 4 32 theme intracellular 540:552 arg1 pathway 566:572 the intracellular trafficking pathway 536:572 the intracellular trafficking pathway 536:572 Here, we show that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc) during the intracellular trafficking pathway. 36943877 5 33 theme endosomal 688:696 arg1 machinery 706:714 the endosomal sorting machinery 684:714 the endosomal sorting machinery 684:714 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 6 34 theme antitumor 883:891 arg1 immunity 893:900 T cell-mediated antitumor immunity in vitro 867:909 T cell-mediated antitumor immunity in vitro 867:909 O-GlcNAc inhibition activates T cell-mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. 36943877 1 35 theme cell-dependent 181:194 arg1 immunity 196:203 T cell-dependent immunity 179:203 T cell-dependent immunity against tumors 179:218 Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. 36943877 3 36 theme PD-L1 389:393 arg1 regulation 362:371 the regulation 358:371 the regulation of cell surface PD-L1 358:393 However, the regulation of cell surface PD-L1 is still poorly understood. 36943877 5 37 theme sorting 698:704 arg1 machinery 706:714 the endosomal sorting machinery 684:714 the endosomal sorting machinery 684:714 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 6 38 theme cell-mediated 869:881 arg1 immunity 893:900 T cell-mediated antitumor immunity in vitro 867:909 T cell-mediated antitumor immunity in vitro 867:909 O-GlcNAc inhibition activates T cell-mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. 36943877 8 39 theme peptide 1122:1128 arg1 inhibitor 1130:1138 a competitive peptide inhibitor 1108:1138 a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells 1108:1249 We also designed a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells. 36943877 8 40 theme PD-L1 1176:1180 arg1 expression 1182:1191 PD-L1 expression 1176:1191 PD-L1 expression 1176:1191 We also designed a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells. 36943877 6 41 theme HGS 965:967 arg1 glycosylation 969:981 HGS glycosylation 965:981 HGS glycosylation 965:981 O-GlcNAc inhibition activates T cell-mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. 36943877 5 42 theme machinery 706:714 arg1 component 671:679 a key component 665:679 a key component of the endosomal sorting machinery 665:714 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 42 theme machinery 706:714 arg1 substrate 648:656 the hepatocyte growth factor-regulated tyrosine kinase substrate 593:656 the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) 593:662 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 6 43 theme T 867:867 arg1 immunity 893:900 T cell-mediated antitumor immunity in vitro 867:909 T cell-mediated antitumor immunity in vitro 867:909 O-GlcNAc inhibition activates T cell-mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. 36943877 3 44 theme cell 376:379 arg1 PD-L1 389:393 cell surface PD-L1 376:393 cell surface PD-L1 376:393 However, the regulation of cell surface PD-L1 is still poorly understood. 36943877 4 45 theme O-linked 489:496 arg1 O-GlcNAc 519:526 O-GlcNAc 519:526 O-GlcNAc 519:526 Here, we show that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc) during the intracellular trafficking pathway. 36943877 4 45 theme O-linked 489:496 arg1 N-acetylglucosamine 498:516 O-linked N-acetylglucosamine 489:516 O-linked N-acetylglucosamine (O-GlcNAc) 489:527 Here, we show that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc) during the intracellular trafficking pathway. 36943877 0 46 theme lysosomal 66:74 arg1 degradation 76:86 PD-L1 lysosomal degradation 60:86 PD-L1 lysosomal degradation 60:86 O-GlcNAcylation promotes tumor immune evasion by inhibiting PD-L1 lysosomal degradation. 36943877 7 47 theme antitumor 1064:1072 arg1 response 1081:1088 antitumor immune response 1064:1088 antitumor immune response 1064:1088 Combination of O-GlcNAc inhibition with PD-L1 antibody synergistically promotes antitumor immune response. 36943877 2 48 theme therapy 324:330 arg1 PD-L1 342:346 immune checkpoint blockade therapy targeting PD-L1 297:346 immune checkpoint blockade therapy targeting PD-L1 297:346 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 3 49 theme surface 381:387 arg1 PD-L1 389:393 cell surface PD-L1 376:393 cell surface PD-L1 376:393 However, the regulation of cell surface PD-L1 is still poorly understood. 36943877 6 50 theme dependent 952:960 arg1 manner 945:950 a manner 943:950 a manner dependent on HGS glycosylation 943:981 O-GlcNAc inhibition activates T cell-mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. 36943877 5 51 theme key 667:669 arg1 component 671:679 a key component 665:679 a key component of the endosomal sorting machinery 665:714 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 5 51 theme key 667:669 arg1 substrate 648:656 the hepatocyte growth factor-regulated tyrosine kinase substrate 593:656 the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) 593:662 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 9 52 theme immune 1318:1323 arg1 evasion 1325:1331 tumor immune evasion 1312:1331 tumor immune evasion 1312:1331 Collectively, our study reveals a link between O-GlcNAc and tumor immune evasion, and suggests strategies for improving PD-L1-mediated immune checkpoint blockade therapy. 36943877 9 53 theme tumor 1312:1316 arg1 evasion 1325:1331 tumor immune evasion 1312:1331 tumor immune evasion 1312:1331 Collectively, our study reveals a link between O-GlcNAc and tumor immune evasion, and suggests strategies for improving PD-L1-mediated immune checkpoint blockade therapy. 36943877 2 54 theme blockade 315:322 arg1 PD-L1 342:346 immune checkpoint blockade therapy targeting PD-L1 297:346 immune checkpoint blockade therapy targeting PD-L1 297:346 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 7 55 theme immune 1074:1079 arg1 response 1081:1088 antitumor immune response 1064:1088 antitumor immune response 1064:1088 Combination of O-GlcNAc inhibition with PD-L1 antibody synergistically promotes antitumor immune response. 36943877 6 56 theme O-GlcNAc 837:844 arg1 inhibition 846:855 O-GlcNAc inhibition 837:855 O-GlcNAc inhibition 837:855 O-GlcNAc inhibition activates T cell-mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. 36943877 2 57 theme PD-L1 251:255 arg1 determinant 266:276 a key determinant 260:276 a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1 260:346 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 2 57 theme PD-L1 251:255 arg1 abundance 225:233 The abundance 221:233 The abundance of cell surface PD-L1 221:255 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 2 58 theme checkpoint 304:313 arg1 PD-L1 342:346 immune checkpoint blockade therapy targeting PD-L1 297:346 immune checkpoint blockade therapy targeting PD-L1 297:346 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 2 59 theme surface 243:249 arg1 PD-L1 251:255 cell surface PD-L1 238:255 cell surface PD-L1 238:255 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 1 60 theme receptor 131:138 arg1 death 156:160 its receptor programmed cell death 1 127:162 its receptor programmed cell death 1 (PD-1) 127:169 Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. 36943877 1 60 theme receptor 131:138 arg1 PD-1 165:168 PD-1 165:168 PD-1 165:168 Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. 36943877 6 61 from mice 935:938 arg1 manner 945:950 a manner 943:950 a manner dependent on HGS glycosylation 943:981 O-GlcNAc inhibition activates T cell-mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. 36943877 9 62 theme blockade 1405:1412 arg1 therapy 1414:1420 PD-L1-mediated immune checkpoint blockade therapy 1372:1420 PD-L1-mediated immune checkpoint blockade therapy 1372:1420 Collectively, our study reveals a link between O-GlcNAc and tumor immune evasion, and suggests strategies for improving PD-L1-mediated immune checkpoint blockade therapy. 36943877 2 63 theme cell 238:241 arg1 PD-L1 251:255 cell surface PD-L1 238:255 cell surface PD-L1 238:255 The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. 36943877 7 64 theme PD-L1 1024:1028 arg1 antibody 1030:1037 PD-L1 antibody 1024:1037 PD-L1 antibody 1024:1037 Combination of O-GlcNAc inhibition with PD-L1 antibody synergistically promotes antitumor immune response. 36943877 1 65 theme programmed 140:149 arg1 death 156:160 its receptor programmed cell death 1 127:162 its receptor programmed cell death 1 (PD-1) 127:169 Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. 36943877 1 65 theme programmed 140:149 arg1 PD-1 165:168 PD-1 165:168 PD-1 165:168 Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. 36943877 0 66 theme PD-L1 60:64 arg1 degradation 76:86 PD-L1 lysosomal degradation 60:86 PD-L1 lysosomal degradation 60:86 O-GlcNAcylation promotes tumor immune evasion by inhibiting PD-L1 lysosomal degradation. 36943877 5 67 with interaction 747:757 arg1 PD-L1 778:782 intracellular PD-L1 764:782 intracellular PD-L1 764:782 O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. 36943877 7 68 theme O-GlcNAc 999:1006 arg1 inhibition 1008:1017 O-GlcNAc inhibition 999:1017 O-GlcNAc inhibition 999:1017 Combination of O-GlcNAc inhibition with PD-L1 antibody synergistically promotes antitumor immune response. 36943877 1 69 theme cell 151:154 arg1 death 156:160 its receptor programmed cell death 1 127:162 its receptor programmed cell death 1 (PD-1) 127:169 Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. 36943877 1 69 theme cell 151:154 arg1 PD-1 165:168 PD-1 165:168 PD-1 165:168 Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. 37120927 9 0 theme cell-specific 1459:1471 arg1 isoform 1481:1487 the muscle cell-specific CaMKIIβ isoform 1448:1487 the muscle cell-specific CaMKIIβ isoform 1448:1487 Immunoblot showed that CaMKIIδ and calmodulin expression are increased but the autophosphorylation of CaMKIIδ and the muscle cell-specific CaMKIIβ isoform are reduced by 75% or more when O-GlcNAcylation is inhibited. 37120927 1 1 theme dependent 177:185 arg1 facilitation 144:155 Ca2+ dependent facilitation 129:155 Ca2+ dependent facilitation (CDF) 129:161 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 1 theme dependent 177:185 arg1 mechanisms 236:245 regulatory mechanisms 225:245 regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration 225:341 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 1 theme dependent 177:185 arg1 acceleration 187:198 frequency dependent acceleration 167:198 frequency dependent acceleration of relaxation (FDAR) 167:219 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 2 theme channel 282:288 arg1 function 290:297 cardiomyocyte Ca2+ channel function 263:297 cardiomyocyte Ca2+ channel function 263:297 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 10 3 theme dependent 1749:1757 arg1 manner 1759:1764 a Ca2+ dependent manner 1742:1764 a Ca2+ dependent manner 1742:1764 We also show that the enzyme responsible for O-GlcNAcylation (OGT) can likely be localized in the dyad space and/or at the cardiac sarcoplasmic reticulum and is precipitated by calmodulin in a Ca2+ dependent manner. 37120927 11 4 theme EC 1892:1893 arg1 coupling 1895:1902 impact cardiomyocyte EC coupling 1871:1902 impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states 1871:1962 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 11 5 theme cardiomyocyte 1878:1890 arg1 coupling 1895:1902 impact cardiomyocyte EC coupling 1871:1902 impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states 1871:1962 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 11 6 theme impact 1871:1876 arg1 coupling 1895:1902 impact cardiomyocyte EC coupling 1871:1902 impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states 1871:1962 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 10 7 theme dyad 1649:1652 arg1 space 1654:1658 the dyad space 1645:1658 the dyad space 1645:1658 We also show that the enzyme responsible for O-GlcNAcylation (OGT) can likely be localized in the dyad space and/or at the cardiac sarcoplasmic reticulum and is precipitated by calmodulin in a Ca2+ dependent manner. 37120927 5 8 link O-linked 802:809 arg1 modification 867:878 a post-translational modification 846:878 a post-translational modification that acts as a signaling molecule and metabolic sensor 846:933 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 5 8 link O-linked 802:809 arg1 O-GlcNAcylation 826:840 O-GlcNAcylation 826:840 O-GlcNAcylation 826:840 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 5 8 link O-linked 802:809 arg1 glycosylation 811:823 Intracellular O-linked glycosylation 788:823 Intracellular O-linked glycosylation (O-GlcNAcylation) 788:841 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 7 9 from activity 1141:1148 arg1 setting 1174:1180 a pseudo-physiologic setting 1153:1180 a pseudo-physiologic setting 1153:1180 Here we sought to investigate whether O-GlcNAcylation impacts CDF and FDAR through modulation of CaMKII activity in a pseudo-physiologic setting. 37120927 0 10 theme relaxation 117:126 arg1 acceleration 101:112 frequency dependent acceleration 81:112 frequency dependent acceleration of relaxation 81:126 Reduced O-GlcNAcylation diminishes cardiomyocyte Ca2+ dependent facilitation and frequency dependent acceleration of relaxation. 37120927 0 10 theme relaxation 117:126 arg1 facilitation 64:75 cardiomyocyte Ca2+ dependent facilitation 35:75 cardiomyocyte Ca2+ dependent facilitation 35:75 Reduced O-GlcNAcylation diminishes cardiomyocyte Ca2+ dependent facilitation and frequency dependent acceleration of relaxation. 37120927 10 11 from precipitated 1712:1723 arg1 manner 1759:1764 a Ca2+ dependent manner 1742:1764 a Ca2+ dependent manner 1742:1764 We also show that the enzyme responsible for O-GlcNAcylation (OGT) can likely be localized in the dyad space and/or at the cardiac sarcoplasmic reticulum and is precipitated by calmodulin in a Ca2+ dependent manner. 37120927 1 12 theme depolarization 394:407 arg1 frequency 409:417 depolarization frequency 394:417 depolarization frequency 394:417 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 10 13 theme responsible 1580:1590 arg1 enzyme 1573:1578 the enzyme 1569:1578 the enzyme responsible for O-GlcNAcylation (OGT) 1569:1616 We also show that the enzyme responsible for O-GlcNAcylation (OGT) can likely be localized in the dyad space and/or at the cardiac sarcoplasmic reticulum and is precipitated by calmodulin in a Ca2+ dependent manner. 37120927 4 14 theme post-translational 688:705 arg1 modifications 707:719 post-translational modifications 688:719 post-translational modifications 688:719 CaMKII activity can be modulated by post-translational modifications but if and how these modifications impact CDF and FDAR is unknown. 37120927 8 15 theme reduced 1309:1315 arg1 O-GlcNAcylation 1317:1331 reduced O-GlcNAcylation 1309:1331 reduced O-GlcNAcylation 1309:1331 Using voltage-clamp and Ca2+ photometry we show that cardiomyocyte CDF and FDAR are significantly diminished in conditions of reduced O-GlcNAcylation. 37120927 6 16 theme hyperglycemic 939:951 arg1 conditions 953:962 hyperglycemic conditions 939:962 hyperglycemic conditions 939:962 In hyperglycemic conditions, CaMKII was shown to be O-GlcNAcylated resulting in pathologic activity. 37120927 8 17 dep show 1226:1229 arg1 Using 1183:1187 Using 1183:1187 Using voltage-clamp and Ca2+ photometry 1183:1221 Using voltage-clamp and Ca2+ photometry we show that cardiomyocyte CDF and FDAR are significantly diminished in conditions of reduced O-GlcNAcylation. 37120927 4 18 dep if 725:726 arg1 unknown 779:785 unknown 779:785 unknown 779:785 CaMKII activity can be modulated by post-translational modifications but if and how these modifications impact CDF and FDAR is unknown. 37120927 4 18 dep if 725:726 arg1 impact 756:761 impact 756:761 impact 756:761 CaMKII activity can be modulated by post-translational modifications but if and how these modifications impact CDF and FDAR is unknown. 37120927 1 19 theme relaxation 203:212 arg1 CDF 158:160 CDF 158:160 CDF 158:160 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 19 theme relaxation 203:212 arg1 facilitation 144:155 Ca2+ dependent facilitation 129:155 Ca2+ dependent facilitation (CDF) 129:161 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 19 theme relaxation 203:212 arg1 mechanisms 236:245 regulatory mechanisms 225:245 regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration 225:341 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 19 theme relaxation 203:212 arg1 acceleration 187:198 frequency dependent acceleration 167:198 frequency dependent acceleration of relaxation (FDAR) 167:219 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 2 20 theme increased 485:493 arg1 rates 501:505 increased heart rates 485:505 increased heart rates 485:505 CDF and FDAR likely evolved to maintain EC coupling at increased heart rates. 37120927 6 21 theme pathologic 1016:1025 arg1 activity 1027:1034 pathologic activity 1016:1034 pathologic activity 1016:1034 In hyperglycemic conditions, CaMKII was shown to be O-GlcNAcylated resulting in pathologic activity. 37120927 5 22 theme Intracellular 788:800 arg1 modification 867:878 a post-translational modification 846:878 a post-translational modification that acts as a signaling molecule and metabolic sensor 846:933 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 5 22 theme Intracellular 788:800 arg1 O-GlcNAcylation 826:840 O-GlcNAcylation 826:840 O-GlcNAcylation 826:840 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 5 22 theme Intracellular 788:800 arg1 glycosylation 811:823 Intracellular O-linked glycosylation 788:823 Intracellular O-linked glycosylation (O-GlcNAcylation) 788:841 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 10 23 theme sarcoplasmic 1682:1693 arg1 reticulum 1695:1703 the cardiac sarcoplasmic reticulum 1670:1703 the cardiac sarcoplasmic reticulum 1670:1703 We also show that the enzyme responsible for O-GlcNAcylation (OGT) can likely be localized in the dyad space and/or at the cardiac sarcoplasmic reticulum and is precipitated by calmodulin in a Ca2+ dependent manner. 37120927 0 24 theme Reduced 0:6 arg1 O-GlcNAcylation 8:22 Reduced O-GlcNAcylation 0:22 Reduced O-GlcNAcylation 0:22 Reduced O-GlcNAcylation diminishes cardiomyocyte Ca2+ dependent facilitation and frequency dependent acceleration of relaxation. 37120927 7 25 theme pseudo-physiologic 1155:1172 arg1 setting 1174:1180 a pseudo-physiologic setting 1153:1180 a pseudo-physiologic setting 1153:1180 Here we sought to investigate whether O-GlcNAcylation impacts CDF and FDAR through modulation of CaMKII activity in a pseudo-physiologic setting. 37120927 0 26 theme cardiomyocyte 35:47 arg1 facilitation 64:75 cardiomyocyte Ca2+ dependent facilitation 35:75 cardiomyocyte Ca2+ dependent facilitation 35:75 Reduced O-GlcNAcylation diminishes cardiomyocyte Ca2+ dependent facilitation and frequency dependent acceleration of relaxation. 37120927 9 27 theme muscle 1452:1457 arg1 isoform 1481:1487 the muscle cell-specific CaMKIIβ isoform 1448:1487 the muscle cell-specific CaMKIIβ isoform 1448:1487 Immunoblot showed that CaMKIIδ and calmodulin expression are increased but the autophosphorylation of CaMKIIδ and the muscle cell-specific CaMKIIβ isoform are reduced by 75% or more when O-GlcNAcylation is inhibited. 37120927 7 28 theme activity 1141:1148 arg1 modulation 1120:1129 modulation 1120:1129 modulation of CaMKII activity in a pseudo-physiologic setting 1120:1180 Here we sought to investigate whether O-GlcNAcylation impacts CDF and FDAR through modulation of CaMKII activity in a pseudo-physiologic setting. 37120927 10 29 located localized 1632:1640 arg2 enzyme 1573:1578 the enzyme 1569:1578 the enzyme responsible for O-GlcNAcylation (OGT) 1569:1616 We also show that the enzyme responsible for O-GlcNAcylation (OGT) can likely be localized in the dyad space and/or at the cardiac sarcoplasmic reticulum and is precipitated by calmodulin in a Ca2+ dependent manner. 37120927 10 29 located localized 1632:1640 arg1 space 1654:1658 the dyad space 1645:1658 the dyad space 1645:1658 We also show that the enzyme responsible for O-GlcNAcylation (OGT) can likely be localized in the dyad space and/or at the cardiac sarcoplasmic reticulum and is precipitated by calmodulin in a Ca2+ dependent manner. 37120927 2 30 theme EC 470:471 arg1 coupling 473:480 EC coupling 470:480 EC coupling 470:480 CDF and FDAR likely evolved to maintain EC coupling at increased heart rates. 37120927 7 31 from setting 1174:1180 arg1 modulation 1120:1129 modulation 1120:1129 modulation of CaMKII activity in a pseudo-physiologic setting 1120:1180 Here we sought to investigate whether O-GlcNAcylation impacts CDF and FDAR through modulation of CaMKII activity in a pseudo-physiologic setting. 37120927 11 32 theme important 1792:1800 arg1 implications 1802:1813 important implications 1792:1813 important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated 1792:2011 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 1 33 theme dependent 134:142 arg1 CDF 158:160 CDF 158:160 CDF 158:160 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 33 theme dependent 134:142 arg1 facilitation 144:155 Ca2+ dependent facilitation 129:155 Ca2+ dependent facilitation (CDF) 129:161 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 33 theme dependent 134:142 arg1 acceleration 187:198 frequency dependent acceleration 167:198 frequency dependent acceleration of relaxation (FDAR) 167:219 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 33 theme dependent 134:142 arg1 mechanisms 236:245 regulatory mechanisms 225:245 regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration 225:341 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 3 34 theme Ca2+/calmodulin-dependent 508:532 arg1 kinase 534:539 Ca2+/calmodulin-dependent kinase II 508:542 Ca2+/calmodulin-dependent kinase II (CaMKII) 508:551 Ca2+/calmodulin-dependent kinase II (CaMKII) was shown to be indispensable to both; however, the mechanisms remain to be completely elucidated. 37120927 3 34 theme Ca2+/calmodulin-dependent 508:532 arg1 CaMKII 545:550 CaMKII 545:550 CaMKII 545:550 Ca2+/calmodulin-dependent kinase II (CaMKII) was shown to be indispensable to both; however, the mechanisms remain to be completely elucidated. 37120927 0 35 theme dependent 54:62 arg1 facilitation 64:75 cardiomyocyte Ca2+ dependent facilitation 35:75 cardiomyocyte Ca2+ dependent facilitation 35:75 Reduced O-GlcNAcylation diminishes cardiomyocyte Ca2+ dependent facilitation and frequency dependent acceleration of relaxation. 37120927 1 36 theme Ca2+ 324:327 arg1 sequestration 329:341 Ca2+ sequestration 324:341 Ca2+ sequestration 324:341 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 5 37 theme signaling 895:903 arg1 modification 867:878 a post-translational modification 846:878 a post-translational modification that acts as a signaling molecule and metabolic sensor 846:933 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 5 37 theme signaling 895:903 arg1 molecule 905:912 a signaling molecule 893:912 a signaling molecule 893:912 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 1 38 theme regulatory 225:234 arg1 facilitation 144:155 Ca2+ dependent facilitation 129:155 Ca2+ dependent facilitation (CDF) 129:161 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 38 theme regulatory 225:234 arg1 acceleration 187:198 frequency dependent acceleration 167:198 frequency dependent acceleration of relaxation (FDAR) 167:219 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 1 38 theme regulatory 225:234 arg1 mechanisms 236:245 regulatory mechanisms 225:245 regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration 225:341 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 0 39 theme Ca2+ 49:52 arg1 facilitation 64:75 cardiomyocyte Ca2+ dependent facilitation 35:75 cardiomyocyte Ca2+ dependent facilitation 35:75 Reduced O-GlcNAcylation diminishes cardiomyocyte Ca2+ dependent facilitation and frequency dependent acceleration of relaxation. 37120927 1 40 theme sequestration 329:341 arg1 rate 316:319 the rate 312:319 the rate of Ca2+ sequestration 312:341 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 7 41 theme CaMKII 1134:1139 arg1 activity 1141:1148 CaMKII activity 1134:1148 CaMKII activity in a pseudo-physiologic setting 1134:1180 Here we sought to investigate whether O-GlcNAcylation impacts CDF and FDAR through modulation of CaMKII activity in a pseudo-physiologic setting. 37120927 1 42 theme cardiomyocyte 263:275 arg1 function 290:297 cardiomyocyte Ca2+ channel function 263:297 cardiomyocyte Ca2+ channel function 263:297 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 8 43 theme O-GlcNAcylation 1317:1331 arg1 conditions 1295:1304 conditions 1295:1304 conditions of reduced O-GlcNAcylation 1295:1331 Using voltage-clamp and Ca2+ photometry we show that cardiomyocyte CDF and FDAR are significantly diminished in conditions of reduced O-GlcNAcylation. 37120927 11 44 theme normal 1907:1912 arg1 settings 1926:1933 normal physiologic settings 1907:1933 normal physiologic settings 1907:1933 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 9 45 theme CaMKIIδ 1436:1442 arg1 isoform 1481:1487 the muscle cell-specific CaMKIIβ isoform 1448:1487 the muscle cell-specific CaMKIIβ isoform 1448:1487 Immunoblot showed that CaMKIIδ and calmodulin expression are increased but the autophosphorylation of CaMKIIδ and the muscle cell-specific CaMKIIβ isoform are reduced by 75% or more when O-GlcNAcylation is inhibited. 37120927 9 45 theme CaMKIIδ 1436:1442 arg1 autophosphorylation 1413:1431 the autophosphorylation 1409:1431 the autophosphorylation of CaMKIIδ 1409:1442 Immunoblot showed that CaMKIIδ and calmodulin expression are increased but the autophosphorylation of CaMKIIδ and the muscle cell-specific CaMKIIβ isoform are reduced by 75% or more when O-GlcNAcylation is inhibited. 37120927 11 46 theme disease 1949:1955 arg1 states 1957:1962 disease states 1949:1962 disease states 1949:1962 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 2 47 theme heart 495:499 arg1 rates 501:505 increased heart rates 485:505 increased heart rates 485:505 CDF and FDAR likely evolved to maintain EC coupling at increased heart rates. 37120927 11 48 theme physiologic 1914:1924 arg1 settings 1926:1933 normal physiologic settings 1907:1933 normal physiologic settings 1907:1933 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 11 49 from coupling 1895:1902 arg1 settings 1926:1933 normal physiologic settings 1907:1933 normal physiologic settings 1907:1933 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 11 49 from coupling 1895:1902 arg1 states 1957:1962 disease states 1949:1962 disease states 1949:1962 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 1 50 theme Ca2+-release 355:366 arg1 event 368:372 a Ca2+-release event 353:372 a Ca2+-release event 353:372 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 37120927 8 51 theme Ca2+ 1207:1210 arg1 photometry 1212:1221 Ca2+ photometry 1207:1221 Ca2+ photometry 1207:1221 Using voltage-clamp and Ca2+ photometry we show that cardiomyocyte CDF and FDAR are significantly diminished in conditions of reduced O-GlcNAcylation. 37120927 8 52 theme cardiomyocyte 1236:1248 arg1 CDF 1250:1252 cardiomyocyte CDF 1236:1252 cardiomyocyte CDF 1236:1252 Using voltage-clamp and Ca2+ photometry we show that cardiomyocyte CDF and FDAR are significantly diminished in conditions of reduced O-GlcNAcylation. 37120927 9 53 theme CaMKIIβ 1473:1479 arg1 isoform 1481:1487 the muscle cell-specific CaMKIIβ isoform 1448:1487 the muscle cell-specific CaMKIIβ isoform 1448:1487 Immunoblot showed that CaMKIIδ and calmodulin expression are increased but the autophosphorylation of CaMKIIδ and the muscle cell-specific CaMKIIβ isoform are reduced by 75% or more when O-GlcNAcylation is inhibited. 37120927 9 54 theme calmodulin 1369:1378 arg1 expression 1380:1389 calmodulin expression 1369:1389 calmodulin expression 1369:1389 Immunoblot showed that CaMKIIδ and calmodulin expression are increased but the autophosphorylation of CaMKIIδ and the muscle cell-specific CaMKIIβ isoform are reduced by 75% or more when O-GlcNAcylation is inhibited. 37120927 0 55 theme dependent 91:99 arg1 acceleration 101:112 frequency dependent acceleration 81:112 frequency dependent acceleration of relaxation 81:126 Reduced O-GlcNAcylation diminishes cardiomyocyte Ca2+ dependent facilitation and frequency dependent acceleration of relaxation. 37120927 10 56 from manner 1759:1764 arg1 precipitated 1712:1723 precipitated 1712:1723 precipitated 1712:1723 We also show that the enzyme responsible for O-GlcNAcylation (OGT) can likely be localized in the dyad space and/or at the cardiac sarcoplasmic reticulum and is precipitated by calmodulin in a Ca2+ dependent manner. 37120927 5 57 theme metabolic 918:926 arg1 sensor 928:933 metabolic sensor 918:933 metabolic sensor 918:933 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 4 58 theme CaMKII 652:657 arg1 activity 659:666 CaMKII activity 652:666 CaMKII activity 652:666 CaMKII activity can be modulated by post-translational modifications but if and how these modifications impact CDF and FDAR is unknown. 37120927 5 59 theme O-linked 802:809 arg1 modification 867:878 a post-translational modification 846:878 a post-translational modification that acts as a signaling molecule and metabolic sensor 846:933 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 5 59 theme O-linked 802:809 arg1 O-GlcNAcylation 826:840 O-GlcNAcylation 826:840 O-GlcNAcylation 826:840 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 5 59 theme O-linked 802:809 arg1 glycosylation 811:823 Intracellular O-linked glycosylation 788:823 Intracellular O-linked glycosylation (O-GlcNAcylation) 788:841 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 7 60 from modulation 1120:1129 arg1 setting 1174:1180 a pseudo-physiologic setting 1153:1180 a pseudo-physiologic setting 1153:1180 Here we sought to investigate whether O-GlcNAcylation impacts CDF and FDAR through modulation of CaMKII activity in a pseudo-physiologic setting. 37120927 10 61 theme cardiac 1674:1680 arg1 reticulum 1695:1703 the cardiac sarcoplasmic reticulum 1670:1703 the cardiac sarcoplasmic reticulum 1670:1703 We also show that the enzyme responsible for O-GlcNAcylation (OGT) can likely be localized in the dyad space and/or at the cardiac sarcoplasmic reticulum and is precipitated by calmodulin in a Ca2+ dependent manner. 37120927 5 62 theme post-translational 848:865 arg1 modification 867:878 a post-translational modification 846:878 a post-translational modification that acts as a signaling molecule and metabolic sensor 846:933 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 5 62 theme post-translational 848:865 arg1 molecule 905:912 a signaling molecule 893:912 a signaling molecule 893:912 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 5 62 theme post-translational 848:865 arg1 glycosylation 811:823 Intracellular O-linked glycosylation 788:823 Intracellular O-linked glycosylation (O-GlcNAcylation) 788:841 Intracellular O-linked glycosylation (O-GlcNAcylation) is a post-translational modification that acts as a signaling molecule and metabolic sensor. 37120927 11 63 contain have 1787:1790 arg2 implications 1802:1813 important implications 1792:1813 important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated 1792:2011 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 11 63 contain have 1787:1790 arg1 findings 1773:1780 These findings 1767:1780 These findings 1767:1780 These findings will have important implications for our understanding of how CaMKII and OGT interact to impact cardiomyocyte EC coupling in normal physiologic settings as well as in disease states where CaMKII and OGT may be aberrantly regulated. 37120927 1 64 theme Ca2+ 277:280 arg1 function 290:297 cardiomyocyte Ca2+ channel function 263:297 cardiomyocyte Ca2+ channel function 263:297 Ca2+ dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca2+ channel function and increase the rate of Ca2+ sequestration following a Ca2+-release event, respectively, when depolarization frequency increases. 35207462 6 0 theme immature 1258:1265 arg1 O-glycosylation 1274:1288 immature core 1 O-glycosylation 1258:1288 immature core 1 O-glycosylation 1258:1288 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 6 1 theme core 1267:1270 arg1 O-glycosylation 1274:1288 immature core 1 O-glycosylation 1258:1288 immature core 1 O-glycosylation 1258:1288 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 7 2 from down-regulation 1585:1599 arg1 CCA 1615:1617 CCA 1615:1617 CCA 1615:1617 Our findings demonstrate that down-regulation of C1GALT1 in CCA increases the expression of immature core 1 O-glycan, enhancing CCA progression, including growth and 5-fluorouracil resistance via the activation of the AKT/ERK signaling pathway. 35207462 6 3 theme other 1369:1373 arg1 glycosyltransferases 1389:1408 other main O-linked glycosyltransferases 1369:1408 other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown 1369:1552 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 6 4 theme CCA 1223:1225 arg1 lines 1232:1236 CCA cell lines 1223:1236 CCA cell lines 1223:1236 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 5 5 theme ABC 1030:1032 arg1 genes 1046:1050 ABC transporter genes 1030:1050 ABC transporter genes 1030:1050 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 1 6 theme cholangiocarcinoma 218:235 arg1 CCA 238:240 CCA 238:240 CCA 238:240 Alteration of mucin-type O-glycosylation is implicated in tumor progression and metastasis of cholangiocarcinoma (CCA). 35207462 1 6 theme cholangiocarcinoma 218:235 arg1 metastasis 204:213 metastasis 204:213 metastasis of cholangiocarcinoma (CCA) 204:241 Alteration of mucin-type O-glycosylation is implicated in tumor progression and metastasis of cholangiocarcinoma (CCA). 35207462 1 6 theme cholangiocarcinoma 218:235 arg1 progression 188:198 tumor progression 182:198 tumor progression 182:198 Alteration of mucin-type O-glycosylation is implicated in tumor progression and metastasis of cholangiocarcinoma (CCA). 35207462 4 7 theme CCA 666:668 arg1 tissues 670:676 CCA tissues 666:676 CCA tissues 666:676 Our study demonstrated that C1GALT1 was downregulated in CCA tissues at both the mRNA and protein levels. 35207462 6 8 from knockdown 1544:1552 arg1 β1,3-N-acetylglucosaminyltransferase 1410:1445 β1,3-N-acetylglucosaminyltransferase 1410:1445 β1,3-N-acetylglucosaminyltransferase 1410:1445 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 1 9 theme mucin-type 138:147 arg1 O-glycosylation 149:163 mucin-type O-glycosylation 138:163 mucin-type O-glycosylation 138:163 Alteration of mucin-type O-glycosylation is implicated in tumor progression and metastasis of cholangiocarcinoma (CCA). 35207462 5 10 theme C1GALT1 742:748 arg1 function 730:737 The biological function 715:737 The biological function of C1GALT1 using siRNA 715:760 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 11 theme proteins 1072:1079 arg1 resistance 947:956 5-fluorouracil resistance 932:956 5-fluorouracil resistance in a dose-dependent manner 932:983 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 11 theme proteins 1072:1079 arg1 Induction 892:900 (i) Induction 888:900 (i) Induction of CCA cell proliferation 888:926 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 11 theme proteins 1072:1079 arg1 up-regulation 991:1003 (ii) up-regulation 986:1003 (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins 986:1079 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 2 12 theme β1-3 251:254 arg1 enzyme 301:306 a primary enzyme 291:306 a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans 291:375 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 2 12 theme β1-3 251:254 arg1 C1GALT1 279:285 C1GALT1 279:285 C1GALT1 279:285 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 2 12 theme β1-3 251:254 arg1 Galactosyltransferase 256:276 Core 1 β1-3 Galactosyltransferase 244:276 Core 1 β1-3 Galactosyltransferase (C1GALT1) 244:286 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 6 13 theme silencing 1202:1210 arg1 C1GALT1 1212:1218 silencing C1GALT1 1202:1218 silencing C1GALT1 in CCA cell lines 1202:1236 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 6 14 from β1,3-N-acetylglucosaminyltransferase 1410:1445 arg1 knockdown 1544:1552 C1GALT1 knockdown 1536:1552 C1GALT1 knockdown 1536:1552 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 2 15 theme Core 244:247 arg1 enzyme 301:306 a primary enzyme 291:306 a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans 291:375 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 2 15 theme Core 244:247 arg1 C1GALT1 279:285 C1GALT1 279:285 C1GALT1 279:285 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 2 15 theme Core 244:247 arg1 Galactosyltransferase 256:276 Core 1 β1-3 Galactosyltransferase 244:276 Core 1 β1-3 Galactosyltransferase (C1GALT1) 244:286 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 5 16 theme CCA 905:907 arg1 proliferation 914:926 CCA cell proliferation 905:926 CCA cell proliferation 905:926 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 17 from suppression 780:790 arg1 KKU-055 826:832 KKU-055 826:832 KKU-055 826:832 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 17 from suppression 780:790 arg1 lines 819:823 the CCA cell lines 806:823 the CCA cell lines (KKU-055 and KKU-100) 806:845 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 17 from suppression 780:790 arg1 KKU-100 838:844 KKU-100 838:844 KKU-100 838:844 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 18 theme proliferation 914:926 arg1 resistance 947:956 5-fluorouracil resistance 932:956 5-fluorouracil resistance in a dose-dependent manner 932:983 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 18 theme proliferation 914:926 arg1 Induction 892:900 (i) Induction 888:900 (i) Induction of CCA cell proliferation 888:926 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 18 theme proliferation 914:926 arg1 up-regulation 991:1003 (ii) up-regulation 986:1003 (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins 986:1079 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 7 19 theme pathway 1791:1797 arg1 activation 1755:1764 the activation 1751:1764 the activation of the AKT/ERK signaling pathway 1751:1797 Our findings demonstrate that down-regulation of C1GALT1 in CCA increases the expression of immature core 1 O-glycan, enhancing CCA progression, including growth and 5-fluorouracil resistance via the activation of the AKT/ERK signaling pathway. 35207462 1 20 theme O-glycosylation 149:163 arg1 Alteration 124:133 Alteration 124:133 Alteration of mucin-type O-glycosylation 124:163 Alteration of mucin-type O-glycosylation is implicated in tumor progression and metastasis of cholangiocarcinoma (CCA). 35207462 6 21 from C1GALT1 1212:1218 arg1 lines 1232:1236 CCA cell lines 1223:1236 CCA cell lines 1223:1236 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 6 22 theme main 1375:1378 arg1 glycosyltransferases 1389:1408 other main O-linked glycosyltransferases 1369:1408 other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown 1369:1552 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 7 23 theme AKT/ERK 1773:1779 arg1 pathway 1791:1797 the AKT/ERK signaling pathway 1769:1797 the AKT/ERK signaling pathway 1769:1797 Our findings demonstrate that down-regulation of C1GALT1 in CCA increases the expression of immature core 1 O-glycan, enhancing CCA progression, including growth and 5-fluorouracil resistance via the activation of the AKT/ERK signaling pathway. 35207462 5 24 theme genes 1046:1050 arg1 resistance 947:956 5-fluorouracil resistance 932:956 5-fluorouracil resistance in a dose-dependent manner 932:983 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 24 theme genes 1046:1050 arg1 Induction 892:900 (i) Induction 888:900 (i) Induction of CCA cell proliferation 888:926 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 24 theme genes 1046:1050 arg1 up-regulation 991:1003 (ii) up-regulation 986:1003 (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins 986:1079 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 0 25 theme Signaling 104:112 arg1 Pathways 114:121 AKT/ERK Signaling Pathways 96:121 AKT/ERK Signaling Pathways 96:121 Down-Regulation of C1GALT1 Enhances the Progression of Cholangiocarcinoma through Activation of AKT/ERK Signaling Pathways. 35207462 5 26 theme dose-dependent 963:976 arg1 manner 978:983 a dose-dependent manner 961:983 a dose-dependent manner 961:983 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 3 27 theme aberrant 466:473 arg1 O-glycosylation 482:496 aberrant core 1 O-glycosylation 466:496 aberrant core 1 O-glycosylation 466:496 Dysregulation of C1GALT1 has been documented in multiple cancers and is associated with aberrant core 1 O-glycosylation and cancer aggressiveness; however, the expression of C1GALT1 and its role in CCA progression remains unknown. 35207462 6 28 theme VVL-binding 1326:1336 arg1 glycans 1338:1344 VVL-binding glycans 1326:1344 VVL-binding glycans 1326:1344 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 7 29 theme immature 1647:1654 arg1 O-glycan 1663:1670 immature core 1 O-glycan 1647:1670 immature core 1 O-glycan 1647:1670 Our findings demonstrate that down-regulation of C1GALT1 in CCA increases the expression of immature core 1 O-glycan, enhancing CCA progression, including growth and 5-fluorouracil resistance via the activation of the AKT/ERK signaling pathway. 35207462 5 30 theme ERK 1149:1151 arg1 activation/phosphorylation 1111:1136 the activation/phosphorylation 1107:1136 the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells 1107:1178 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 31 theme 5-fluorouracil 932:945 arg1 resistance 947:956 5-fluorouracil resistance 932:956 5-fluorouracil resistance in a dose-dependent manner 932:983 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 0 32 theme C1GALT1 19:25 arg1 Down-Regulation 0:14 Down-Regulation 0:14 Down-Regulation of C1GALT1 0:25 Down-Regulation of C1GALT1 Enhances the Progression of Cholangiocarcinoma through Activation of AKT/ERK Signaling Pathways. 35207462 5 33 theme silencing 1156:1164 arg1 cells 1174:1178 silencing C1GALT1 cells 1156:1178 silencing C1GALT1 cells 1156:1178 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 6 34 dep glycosyltransferases 1389:1408 arg1 β1,3-N-acetylglucosaminyltransferase 1410:1445 β1,3-N-acetylglucosaminyltransferase 1410:1445 β1,3-N-acetylglucosaminyltransferase 1410:1445 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 5 35 theme CCA 810:812 arg1 KKU-055 826:832 KKU-055 826:832 KKU-055 826:832 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 35 theme CCA 810:812 arg1 lines 819:823 the CCA cell lines 806:823 the CCA cell lines (KKU-055 and KKU-100) 806:845 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 35 theme CCA 810:812 arg1 KKU-100 838:844 KKU-100 838:844 KKU-100 838:844 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 36 theme growth-related 1008:1021 arg1 genes 1023:1027 growth-related genes 1008:1027 growth-related genes 1008:1027 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 3 37 theme multiple 426:433 arg1 cancers 435:441 multiple cancers 426:441 multiple cancers 426:441 Dysregulation of C1GALT1 has been documented in multiple cancers and is associated with aberrant core 1 O-glycosylation and cancer aggressiveness; however, the expression of C1GALT1 and its role in CCA progression remains unknown. 35207462 2 38 theme O-glycans 367:375 arg1 elongation 327:336 the elongation 323:336 the elongation of core 1-derived mucin-type O-glycans 323:375 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 6 39 theme glycosyltransferases 1389:1408 arg1 down-regulation 1350:1364 down-regulation 1350:1364 down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown 1350:1552 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 6 39 theme glycosyltransferases 1389:1408 arg1 expression 1312:1321 high expression 1307:1321 high expression of VVL-binding glycans 1307:1344 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 5 40 theme AKT 1141:1143 arg1 activation/phosphorylation 1111:1136 the activation/phosphorylation 1107:1136 the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells 1107:1178 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 2 41 theme 1-derived 346:354 arg1 O-glycans 367:375 core 1-derived mucin-type O-glycans 341:375 core 1-derived mucin-type O-glycans 341:375 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 3 42 dep O-glycosylation 482:496 arg1 aggressiveness 509:522 aggressiveness 509:522 aggressiveness 509:522 Dysregulation of C1GALT1 has been documented in multiple cancers and is associated with aberrant core 1 O-glycosylation and cancer aggressiveness; however, the expression of C1GALT1 and its role in CCA progression remains unknown. 35207462 0 43 theme Cholangiocarcinoma 55:72 arg1 Progression 40:50 the Progression 36:50 the Progression of Cholangiocarcinoma 36:72 Down-Regulation of C1GALT1 Enhances the Progression of Cholangiocarcinoma through Activation of AKT/ERK Signaling Pathways. 35207462 5 44 theme C1GALT1 795:801 arg1 suppression 780:790 suppression 780:790 suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) 780:845 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 45 from AKT 1141:1143 arg1 cells 1174:1178 silencing C1GALT1 cells 1156:1178 silencing C1GALT1 cells 1156:1178 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 6 46 theme cell 1227:1230 arg1 lines 1232:1236 CCA cell lines 1223:1236 CCA cell lines 1223:1236 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 5 47 from activation/phosphorylation 1111:1136 arg1 cells 1174:1178 silencing C1GALT1 cells 1156:1178 silencing C1GALT1 cells 1156:1178 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 3 48 from expression 538:547 arg1 progression 580:590 CCA progression 576:590 CCA progression 576:590 Dysregulation of C1GALT1 has been documented in multiple cancers and is associated with aberrant core 1 O-glycosylation and cancer aggressiveness; however, the expression of C1GALT1 and its role in CCA progression remains unknown. 35207462 6 49 theme N-Acetylgalactosaminide 1466:1488 arg1 Alpha-2,6-Sialyltransferase 1490:1516 ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 1462:1518 ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) 1462:1531 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 6 49 theme N-Acetylgalactosaminide 1466:1488 arg1 ST6GALNAC1 1521:1530 ST6GALNAC1 1521:1530 ST6GALNAC1 1521:1530 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 6 50 dep associated 1242:1251 arg1 demonstrated 1291:1302 demonstrated 1291:1302 demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown 1291:1552 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 2 51 theme primary 293:299 arg1 enzyme 301:306 a primary enzyme 291:306 a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans 291:375 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 2 51 theme primary 293:299 arg1 Galactosyltransferase 256:276 Core 1 β1-3 Galactosyltransferase 244:276 Core 1 β1-3 Galactosyltransferase (C1GALT1) 244:286 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 5 52 from up-regulation 991:1003 arg1 manner 978:983 a dose-dependent manner 961:983 a dose-dependent manner 961:983 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 53 from increase 1095:1102 arg1 activation/phosphorylation 1111:1136 the activation/phosphorylation 1107:1136 the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells 1107:1178 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 54 dep lines 819:823 arg1 KKU-055 826:832 KKU-055 826:832 KKU-055 826:832 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 54 dep lines 819:823 arg1 lines 819:823 the CCA cell lines 806:823 the CCA cell lines (KKU-055 and KKU-100) 806:845 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 54 dep lines 819:823 arg1 KKU-100 838:844 KKU-100 838:844 KKU-100 838:844 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 55 from ERK 1149:1151 arg1 cells 1174:1178 silencing C1GALT1 cells 1156:1178 silencing C1GALT1 cells 1156:1178 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 4 56 theme mRNA 690:693 arg1 levels 707:712 both the mRNA and protein levels 681:712 levels 707:712 Our study demonstrated that C1GALT1 was downregulated in CCA tissues at both the mRNA and protein levels. 35207462 5 57 theme biological 719:728 arg1 function 730:737 The biological function 715:737 The biological function of C1GALT1 using siRNA 715:760 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 3 58 theme CCA 576:578 arg1 progression 580:590 CCA progression 576:590 CCA progression 576:590 Dysregulation of C1GALT1 has been documented in multiple cancers and is associated with aberrant core 1 O-glycosylation and cancer aggressiveness; however, the expression of C1GALT1 and its role in CCA progression remains unknown. 35207462 5 59 dep up-regulation 991:1003 arg1 ii 987:988 ii 987:988 ii 987:988 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 6 60 theme high 1307:1310 arg1 expression 1312:1321 high expression 1307:1321 high expression of VVL-binding glycans 1307:1344 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 5 61 theme anti-apoptotic 1057:1070 arg1 proteins 1072:1079 anti-apoptotic proteins 1057:1079 anti-apoptotic proteins 1057:1079 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 62 theme CCA 857:859 arg1 progression 861:871 CCA progression 857:871 CCA progression 857:871 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 63 from resistance 947:956 arg1 manner 978:983 a dose-dependent manner 961:983 a dose-dependent manner 961:983 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 7 64 theme O-glycan 1663:1670 arg1 expression 1633:1642 the expression 1629:1642 the expression of immature core 1 O-glycan 1629:1670 Our findings demonstrate that down-regulation of C1GALT1 in CCA increases the expression of immature core 1 O-glycan, enhancing CCA progression, including growth and 5-fluorouracil resistance via the activation of the AKT/ERK signaling pathway. 35207462 7 65 theme core 1656:1659 arg1 O-glycan 1663:1670 immature core 1 O-glycan 1647:1670 immature core 1 O-glycan 1647:1670 Our findings demonstrate that down-regulation of C1GALT1 in CCA increases the expression of immature core 1 O-glycan, enhancing CCA progression, including growth and 5-fluorouracil resistance via the activation of the AKT/ERK signaling pathway. 35207462 5 66 theme transporter 1034:1044 arg1 genes 1046:1050 ABC transporter genes 1030:1050 ABC transporter genes 1030:1050 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 67 theme cell 909:912 arg1 proliferation 914:926 CCA cell proliferation 905:926 CCA cell proliferation 905:926 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 6 68 theme O-linked 1380:1387 arg1 glycosyltransferases 1389:1408 other main O-linked glycosyltransferases 1369:1408 other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown 1369:1552 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 4 69 theme protein 699:705 arg1 levels 707:712 both the mRNA and protein levels 681:712 levels 707:712 Our study demonstrated that C1GALT1 was downregulated in CCA tissues at both the mRNA and protein levels. 35207462 0 70 theme AKT/ERK 96:102 arg1 Pathways 114:121 AKT/ERK Signaling Pathways 96:121 AKT/ERK Signaling Pathways 96:121 Down-Regulation of C1GALT1 Enhances the Progression of Cholangiocarcinoma through Activation of AKT/ERK Signaling Pathways. 35207462 1 71 theme tumor 182:186 arg1 progression 188:198 tumor progression 182:198 tumor progression 182:198 Alteration of mucin-type O-glycosylation is implicated in tumor progression and metastasis of cholangiocarcinoma (CCA). 35207462 7 72 theme signaling 1781:1789 arg1 pathway 1791:1797 the AKT/ERK signaling pathway 1769:1797 the AKT/ERK signaling pathway 1769:1797 Our findings demonstrate that down-regulation of C1GALT1 in CCA increases the expression of immature core 1 O-glycan, enhancing CCA progression, including growth and 5-fluorouracil resistance via the activation of the AKT/ERK signaling pathway. 35207462 3 73 from role 568:571 arg1 progression 580:590 CCA progression 576:590 CCA progression 576:590 Dysregulation of C1GALT1 has been documented in multiple cancers and is associated with aberrant core 1 O-glycosylation and cancer aggressiveness; however, the expression of C1GALT1 and its role in CCA progression remains unknown. 35207462 0 74 theme Pathways 114:121 arg1 Activation 82:91 Activation 82:91 Activation of AKT/ERK Signaling Pathways 82:121 Down-Regulation of C1GALT1 Enhances the Progression of Cholangiocarcinoma through Activation of AKT/ERK Signaling Pathways. 35207462 5 75 from Induction 892:900 arg1 manner 978:983 a dose-dependent manner 961:983 a dose-dependent manner 961:983 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 7 76 theme C1GALT1 1604:1610 arg1 down-regulation 1585:1599 down-regulation 1585:1599 down-regulation of C1GALT1 in CCA 1585:1617 Our findings demonstrate that down-regulation of C1GALT1 in CCA increases the expression of immature core 1 O-glycan, enhancing CCA progression, including growth and 5-fluorouracil resistance via the activation of the AKT/ERK signaling pathway. 35207462 3 77 theme C1GALT1 395:401 arg1 Dysregulation 378:390 Dysregulation 378:390 Dysregulation of C1GALT1 378:401 Dysregulation of C1GALT1 has been documented in multiple cancers and is associated with aberrant core 1 O-glycosylation and cancer aggressiveness; however, the expression of C1GALT1 and its role in CCA progression remains unknown. 35207462 6 78 link O-linked 1380:1387 arg1 glycosyltransferases 1389:1408 other main O-linked glycosyltransferases 1369:1408 other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown 1369:1552 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 6 79 theme glycans 1338:1344 arg1 down-regulation 1350:1364 down-regulation 1350:1364 down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown 1350:1552 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 6 79 theme glycans 1338:1344 arg1 expression 1312:1321 high expression 1307:1321 high expression of VVL-binding glycans 1307:1344 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 3 80 theme core 475:478 arg1 O-glycosylation 482:496 aberrant core 1 O-glycosylation 466:496 aberrant core 1 O-glycosylation 466:496 Dysregulation of C1GALT1 has been documented in multiple cancers and is associated with aberrant core 1 O-glycosylation and cancer aggressiveness; however, the expression of C1GALT1 and its role in CCA progression remains unknown. 35207462 6 81 theme ST6 1462:1464 arg1 Alpha-2,6-Sialyltransferase 1490:1516 ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 1462:1518 ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) 1462:1531 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 6 81 theme ST6 1462:1464 arg1 ST6GALNAC1 1521:1530 ST6GALNAC1 1521:1530 ST6GALNAC1 1521:1530 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 7 82 theme CCA 1683:1685 arg1 progression 1687:1697 CCA progression 1683:1697 CCA progression 1683:1697 Our findings demonstrate that down-regulation of C1GALT1 in CCA increases the expression of immature core 1 O-glycan, enhancing CCA progression, including growth and 5-fluorouracil resistance via the activation of the AKT/ERK signaling pathway. 35207462 5 83 from cells 1174:1178 arg1 activation/phosphorylation 1111:1136 the activation/phosphorylation 1107:1136 the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells 1107:1178 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 84 dep Induction 892:900 arg1 increase 1095:1102 increase 1095:1102 increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells 1095:1178 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 84 dep Induction 892:900 arg1 i 889:889 i 889:889 i 889:889 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 84 dep Induction 892:900 arg1 an 1092:1093 an 1092:1093 an 1092:1093 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 7 85 theme 5-fluorouracil 1721:1734 arg1 resistance 1736:1745 5-fluorouracil resistance 1721:1745 5-fluorouracil resistance 1721:1745 Our findings demonstrate that down-regulation of C1GALT1 in CCA increases the expression of immature core 1 O-glycan, enhancing CCA progression, including growth and 5-fluorouracil resistance via the activation of the AKT/ERK signaling pathway. 35207462 5 86 theme C1GALT1 1166:1172 arg1 cells 1174:1178 silencing C1GALT1 cells 1156:1178 silencing C1GALT1 cells 1156:1178 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 87 theme cell 814:817 arg1 KKU-055 826:832 KKU-055 826:832 KKU-055 826:832 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 87 theme cell 814:817 arg1 lines 819:823 the CCA cell lines 806:823 the CCA cell lines (KKU-055 and KKU-100) 806:845 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 87 theme cell 814:817 arg1 KKU-100 838:844 KKU-100 838:844 KKU-100 838:844 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 88 theme genes 1023:1027 arg1 resistance 947:956 5-fluorouracil resistance 932:956 5-fluorouracil resistance in a dose-dependent manner 932:983 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 88 theme genes 1023:1027 arg1 Induction 892:900 (i) Induction 888:900 (i) Induction of CCA cell proliferation 888:926 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 5 88 theme genes 1023:1027 arg1 up-regulation 991:1003 (ii) up-regulation 986:1003 (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins 986:1079 The biological function of C1GALT1 using siRNA demonstrated that suppression of C1GALT1 in the CCA cell lines (KKU-055 and KKU-100) increased CCA progression, evidenced by: (i) Induction of CCA cell proliferation and 5-fluorouracil resistance in a dose-dependent manner; (ii) up-regulation of growth-related genes, ABC transporter genes, and anti-apoptotic proteins; and (iii) an increase in the activation/phosphorylation of AKT and ERK in silencing C1GALT1 cells. 35207462 2 89 theme mucin-type 356:365 arg1 O-glycans 367:375 core 1-derived mucin-type O-glycans 341:375 core 1-derived mucin-type O-glycans 341:375 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 6 90 theme C1GALT1 1536:1542 arg1 knockdown 1544:1552 C1GALT1 knockdown 1536:1552 C1GALT1 knockdown 1536:1552 We demonstrated that silencing C1GALT1 in CCA cell lines was associated with immature core 1 O-glycosylation, demonstrated by high expression of VVL-binding glycans and down-regulation of other main O-linked glycosyltransferases β1,3-N-acetylglucosaminyltransferase 6 (B3GNT6) and ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) in C1GALT1 knockdown. 35207462 2 91 theme core 341:344 arg1 O-glycans 367:375 core 1-derived mucin-type O-glycans 341:375 core 1-derived mucin-type O-glycans 341:375 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 2 92 link 1-derived 346:354 arg1 O-glycans 367:375 core 1-derived mucin-type O-glycans 341:375 core 1-derived mucin-type O-glycans 341:375 Core 1 β1-3 Galactosyltransferase (C1GALT1) is a primary enzyme that regulates the elongation of core 1-derived mucin-type O-glycans. 35207462 3 93 theme C1GALT1 552:558 arg1 role 568:571 its role 564:571 its role in CCA progression 564:590 Dysregulation of C1GALT1 has been documented in multiple cancers and is associated with aberrant core 1 O-glycosylation and cancer aggressiveness; however, the expression of C1GALT1 and its role in CCA progression remains unknown. 35207462 3 93 theme C1GALT1 552:558 arg1 expression 538:547 the expression 534:547 the expression of C1GALT1 534:558 Dysregulation of C1GALT1 has been documented in multiple cancers and is associated with aberrant core 1 O-glycosylation and cancer aggressiveness; however, the expression of C1GALT1 and its role in CCA progression remains unknown. 36056188 1 0 link O-linked 109:116 arg1 β-N-acetylglucosaminylation 118:144 O-linked β-N-acetylglucosaminylation 109:144 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 109:162 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 0 link O-linked 109:116 arg1 reticulum-phagy 180:194 endoplasmic reticulum-phagy 168:194 endoplasmic reticulum-phagy (ER-phagy) 168:205 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 0 link O-linked 109:116 arg1 mechanisms 260:269 well-characterized conserved adaptive regulatory mechanisms 211:269 well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions 211:358 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 0 link O-linked 109:116 arg1 O-GlcNAcylation 147:161 O-GlcNAcylation 147:161 O-GlcNAcylation 147:161 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 5 1 theme degenerated 843:853 arg1 tissues 858:864 degenerated NP tissues 843:864 degenerated NP tissues 843:864 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 8 2 theme FAM134B 1492:1498 arg1 O-GlcNAcylation 1473:1487 O-GlcNAcylation 1473:1487 O-GlcNAcylation of FAM134B 1473:1498 Mechanistically, FAM134B was determined to be a potential target of OGT, and O-GlcNAcylation of FAM134B notably reduced FAM134B ubiquitination-mediated degradation. 36056188 11 3 from therapeutics 1955:1966 arg1 prevention 1975:1984 IDD prevention 1971:1984 IDD prevention 1971:1984 These findings may provide a new option for O-GlcNAcylation-based therapeutics in IDD prevention. 36056188 4 4 theme O-GlcNAcylation 654:668 arg1 mechanisms 710:719 the related underlying mechanisms 687:719 the related underlying mechanisms in IDD 687:726 In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. 36056188 4 4 theme O-GlcNAcylation 654:668 arg1 function 642:649 the function 638:649 the function of O-GlcNAcylation and ER-phagy 638:681 In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. 36056188 5 5 theme NP 855:856 arg1 tissues 858:864 degenerated NP tissues 843:864 degenerated NP tissues 843:864 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 1 6 dep conditions 349:358 arg1 response 322:329 response 322:329 response 322:329 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 9 7 theme rat 1663:1665 arg1 model 1671:1675 a rat IDD model 1661:1675 a rat IDD model 1661:1675 Correspondingly, the protection conferred by modulating O-GlcNAcylation homeostasis was verified in a rat IDD model. 36056188 2 8 theme wide 433:436 arg1 variety 438:444 a wide variety 431:444 a wide variety of human pathologies 431:465 Abnormalities in O-GlcNAcylation and ER-phagy have been documented in a wide variety of human pathologies. 36056188 2 8 theme wide 433:436 arg1 pathologies 455:465 human pathologies 449:465 human pathologies 449:465 Abnormalities in O-GlcNAcylation and ER-phagy have been documented in a wide variety of human pathologies. 36056188 9 9 theme O-GlcNAcylation 1617:1631 arg1 homeostasis 1633:1643 O-GlcNAcylation homeostasis 1617:1643 O-GlcNAcylation homeostasis 1617:1643 Correspondingly, the protection conferred by modulating O-GlcNAcylation homeostasis was verified in a rat IDD model. 36056188 6 10 theme pharmacological 992:1006 arg1 intervention 1008:1019 specific pharmacological intervention 983:1019 specific pharmacological intervention 983:1019 By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. 36056188 3 11 gly O-GlcNAcylation 485:499 arg1 pathogenesis 532:543 the pathogenesis 528:543 the pathogenesis of intervertebral disc degeneration (IDD) 528:585 However, whether O-GlcNAcylation or ER-phagy is involved in the pathogenesis of intervertebral disc degeneration (IDD) is largely unknown. 36056188 7 12 theme amplified 1369:1377 arg1 O-GlcNAcylation 1379:1393 amplified O-GlcNAcylation 1369:1393 amplified O-GlcNAcylation 1369:1393 Moreover, FAM134B-mediated ER-phagy activation was regulated by O-GlcNAcylation, and suppression of ER-phagy by FAM134B knockdown considerably counteracted the protective effects of amplified O-GlcNAcylation. 36056188 1 13 theme various 334:340 arg1 conditions 349:358 various stress conditions 334:358 various stress conditions 334:358 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 10 14 theme adaptive 1824:1831 arg1 capability 1833:1842 the adaptive capability 1820:1842 the adaptive capability of cells 1820:1851 Our data demonstrated that OGT directly associates with and stabilizes FAM134B and subsequently enhances FAM134B-mediated ER-phagy to enhance the adaptive capability of cells in response to nutrient deficiency. 36056188 6 15 theme specific 983:990 arg1 intervention 1008:1019 specific pharmacological intervention 983:1019 specific pharmacological intervention 983:1019 By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. 36056188 7 16 theme O-GlcNAcylation 1379:1393 arg1 effects 1358:1364 the protective effects 1343:1364 the protective effects of amplified O-GlcNAcylation 1343:1393 Moreover, FAM134B-mediated ER-phagy activation was regulated by O-GlcNAcylation, and suppression of ER-phagy by FAM134B knockdown considerably counteracted the protective effects of amplified O-GlcNAcylation. 36056188 10 17 theme cells 1847:1851 arg1 capability 1833:1842 the adaptive capability 1820:1842 the adaptive capability of cells 1820:1851 Our data demonstrated that OGT directly associates with and stabilizes FAM134B and subsequently enhances FAM134B-mediated ER-phagy to enhance the adaptive capability of cells in response to nutrient deficiency. 36056188 1 18 theme stress 342:347 arg1 conditions 349:358 various stress conditions 334:358 various stress conditions 334:358 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 10 19 theme FAM134B-mediated 1783:1798 arg1 ER-phagy 1800:1807 FAM134B-mediated ER-phagy 1783:1807 FAM134B-mediated ER-phagy to enhance the adaptive capability of cells in response to nutrient deficiency 1783:1886 Our data demonstrated that OGT directly associates with and stabilizes FAM134B and subsequently enhances FAM134B-mediated ER-phagy to enhance the adaptive capability of cells in response to nutrient deficiency. 36056188 8 20 theme ubiquitination-mediated 1524:1546 arg1 degradation 1548:1558 FAM134B ubiquitination-mediated degradation 1516:1558 FAM134B ubiquitination-mediated degradation 1516:1558 Mechanistically, FAM134B was determined to be a potential target of OGT, and O-GlcNAcylation of FAM134B notably reduced FAM134B ubiquitination-mediated degradation. 36056188 10 21 theme nutrient 1868:1875 arg1 deficiency 1877:1886 nutrient deficiency 1868:1886 nutrient deficiency 1868:1886 Our data demonstrated that OGT directly associates with and stabilizes FAM134B and subsequently enhances FAM134B-mediated ER-phagy to enhance the adaptive capability of cells in response to nutrient deficiency. 36056188 1 22 theme well-characterized 211:228 arg1 β-N-acetylglucosaminylation 118:144 O-linked β-N-acetylglucosaminylation 109:144 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 109:162 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 22 theme well-characterized 211:228 arg1 reticulum-phagy 180:194 endoplasmic reticulum-phagy 168:194 endoplasmic reticulum-phagy (ER-phagy) 168:205 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 22 theme well-characterized 211:228 arg1 mechanisms 260:269 well-characterized conserved adaptive regulatory mechanisms 211:269 well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions 211:358 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 7 23 theme protective 1347:1356 arg1 effects 1358:1364 the protective effects 1343:1364 the protective effects of amplified O-GlcNAcylation 1343:1393 Moreover, FAM134B-mediated ER-phagy activation was regulated by O-GlcNAcylation, and suppression of ER-phagy by FAM134B knockdown considerably counteracted the protective effects of amplified O-GlcNAcylation. 36056188 6 24 theme cell 1129:1132 arg1 survival 1134:1141 cell survival 1129:1141 cell survival 1129:1141 By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. 36056188 7 25 theme FAM134B-mediated 1197:1212 arg1 activation 1223:1232 FAM134B-mediated ER-phagy activation 1197:1232 FAM134B-mediated ER-phagy activation 1197:1232 Moreover, FAM134B-mediated ER-phagy activation was regulated by O-GlcNAcylation, and suppression of ER-phagy by FAM134B knockdown considerably counteracted the protective effects of amplified O-GlcNAcylation. 36056188 6 26 theme nutrient 1149:1156 arg1 ND 1171:1172 ND 1171:1172 ND 1171:1172 By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. 36056188 6 26 theme nutrient 1149:1156 arg1 deprivation 1158:1168 nutrient deprivation 1149:1168 nutrient deprivation (ND) conditions 1149:1184 By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. 36056188 1 27 theme conserved 230:238 arg1 β-N-acetylglucosaminylation 118:144 O-linked β-N-acetylglucosaminylation 109:144 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 109:162 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 27 theme conserved 230:238 arg1 reticulum-phagy 180:194 endoplasmic reticulum-phagy 168:194 endoplasmic reticulum-phagy (ER-phagy) 168:205 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 27 theme conserved 230:238 arg1 mechanisms 260:269 well-characterized conserved adaptive regulatory mechanisms 211:269 well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions 211:358 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 4 28 from function 642:649 arg1 IDD 724:726 IDD 724:726 IDD 724:726 In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. 36056188 6 29 theme genetic 958:964 arg1 manipulation 966:977 genetic manipulation 958:977 genetic manipulation 958:977 By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. 36056188 7 30 theme ER-phagy 1214:1221 arg1 activation 1223:1232 FAM134B-mediated ER-phagy activation 1197:1232 FAM134B-mediated ER-phagy activation 1197:1232 Moreover, FAM134B-mediated ER-phagy activation was regulated by O-GlcNAcylation, and suppression of ER-phagy by FAM134B knockdown considerably counteracted the protective effects of amplified O-GlcNAcylation. 36056188 1 31 theme O-linked 109:116 arg1 β-N-acetylglucosaminylation 118:144 O-linked β-N-acetylglucosaminylation 109:144 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 109:162 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 31 theme O-linked 109:116 arg1 reticulum-phagy 180:194 endoplasmic reticulum-phagy 168:194 endoplasmic reticulum-phagy (ER-phagy) 168:205 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 31 theme O-linked 109:116 arg1 mechanisms 260:269 well-characterized conserved adaptive regulatory mechanisms 211:269 well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions 211:358 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 31 theme O-linked 109:116 arg1 O-GlcNAcylation 147:161 O-GlcNAcylation 147:161 O-GlcNAcylation 147:161 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 32 theme adaptive 240:247 arg1 β-N-acetylglucosaminylation 118:144 O-linked β-N-acetylglucosaminylation 109:144 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 109:162 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 32 theme adaptive 240:247 arg1 reticulum-phagy 180:194 endoplasmic reticulum-phagy 168:194 endoplasmic reticulum-phagy (ER-phagy) 168:205 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 32 theme adaptive 240:247 arg1 mechanisms 260:269 well-characterized conserved adaptive regulatory mechanisms 211:269 well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions 211:358 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 0 33 theme O-GlcNAc 0:7 arg1 transferase 9:19 O-GlcNAc transferase 0:19 O-GlcNAc transferase 0:19 O-GlcNAc transferase regulates intervertebral disc degeneration by targeting FAM134B-mediated ER-phagy. 36056188 6 34 theme cell 1099:1102 arg1 function 1104:1111 cell function 1099:1111 cell function 1099:1111 By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. 36056188 2 35 theme pathologies 455:465 arg1 variety 438:444 a wide variety 431:444 a wide variety of human pathologies 431:465 Abnormalities in O-GlcNAcylation and ER-phagy have been documented in a wide variety of human pathologies. 36056188 2 35 theme pathologies 455:465 arg1 pathologies 455:465 human pathologies 449:465 human pathologies 449:465 Abnormalities in O-GlcNAcylation and ER-phagy have been documented in a wide variety of human pathologies. 36056188 0 36 theme intervertebral 31:44 arg1 degeneration 51:62 intervertebral disc degeneration 31:62 intervertebral disc degeneration 31:62 O-GlcNAc transferase regulates intervertebral disc degeneration by targeting FAM134B-mediated ER-phagy. 36056188 3 37 theme intervertebral 548:561 arg1 IDD 582:584 IDD 582:584 IDD 582:584 However, whether O-GlcNAcylation or ER-phagy is involved in the pathogenesis of intervertebral disc degeneration (IDD) is largely unknown. 36056188 3 37 theme intervertebral 548:561 arg1 degeneration 568:579 intervertebral disc degeneration 548:579 intervertebral disc degeneration (IDD) 548:585 However, whether O-GlcNAcylation or ER-phagy is involved in the pathogenesis of intervertebral disc degeneration (IDD) is largely unknown. 36056188 5 38 theme O-GlcNAc 790:797 arg1 OGT 812:814 OGT 812:814 OGT 812:814 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 5 38 theme O-GlcNAc 790:797 arg1 transferase 799:809 O-GlcNAc transferase 790:809 O-GlcNAc transferase (OGT) 790:815 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 4 39 from mechanisms 710:719 arg1 IDD 724:726 IDD 724:726 IDD 724:726 In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. 36056188 3 40 theme disc 563:566 arg1 IDD 582:584 IDD 582:584 IDD 582:584 However, whether O-GlcNAcylation or ER-phagy is involved in the pathogenesis of intervertebral disc degeneration (IDD) is largely unknown. 36056188 3 40 theme disc 563:566 arg1 degeneration 568:579 intervertebral disc degeneration 548:579 intervertebral disc degeneration (IDD) 548:585 However, whether O-GlcNAcylation or ER-phagy is involved in the pathogenesis of intervertebral disc degeneration (IDD) is largely unknown. 36056188 7 41 theme ER-phagy 1287:1294 arg1 suppression 1272:1282 suppression 1272:1282 suppression of ER-phagy by FAM134B knockdown 1272:1315 Moreover, FAM134B-mediated ER-phagy activation was regulated by O-GlcNAcylation, and suppression of ER-phagy by FAM134B knockdown considerably counteracted the protective effects of amplified O-GlcNAcylation. 36056188 5 42 theme transferase 799:809 arg1 profiles 758:765 the expression profiles 743:765 the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) 743:815 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 1 43 theme regulatory 249:258 arg1 β-N-acetylglucosaminylation 118:144 O-linked β-N-acetylglucosaminylation 109:144 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 109:162 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 43 theme regulatory 249:258 arg1 reticulum-phagy 180:194 endoplasmic reticulum-phagy 168:194 endoplasmic reticulum-phagy (ER-phagy) 168:205 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 43 theme regulatory 249:258 arg1 mechanisms 260:269 well-characterized conserved adaptive regulatory mechanisms 211:269 well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions 211:358 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 8 44 theme potential 1444:1452 arg1 target 1454:1459 a potential target 1442:1459 a potential target of OGT 1442:1466 Mechanistically, FAM134B was determined to be a potential target of OGT, and O-GlcNAcylation of FAM134B notably reduced FAM134B ubiquitination-mediated degradation. 36056188 8 44 theme potential 1444:1452 arg1 FAM134B 1413:1419 FAM134B 1413:1419 FAM134B 1413:1419 Mechanistically, FAM134B was determined to be a potential target of OGT, and O-GlcNAcylation of FAM134B notably reduced FAM134B ubiquitination-mediated degradation. 36056188 0 45 theme disc 46:49 arg1 degeneration 51:62 intervertebral disc degeneration 31:62 intervertebral disc degeneration 31:62 O-GlcNAc transferase regulates intervertebral disc degeneration by targeting FAM134B-mediated ER-phagy. 36056188 6 46 theme O-GlcNAcylation 1050:1064 arg1 abundance 1066:1074 O-GlcNAcylation abundance 1050:1074 O-GlcNAcylation abundance 1050:1074 By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. 36056188 6 47 theme O-GlcNAc 935:942 arg1 level 944:948 the O-GlcNAc level 931:948 the O-GlcNAc level 931:948 By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. 36056188 5 48 theme NP 906:907 arg1 cells 910:914 nutrient-deprived nucleus pulposus (NP) cells 870:914 nutrient-deprived nucleus pulposus (NP) cells 870:914 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 1 49 theme cellular 285:292 arg1 homeostasis 294:304 cellular homeostasis 285:304 cellular homeostasis 285:304 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 5 50 theme nutrient-deprived 870:886 arg1 cells 910:914 nutrient-deprived nucleus pulposus (NP) cells 870:914 nutrient-deprived nucleus pulposus (NP) cells 870:914 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 5 51 theme expression 747:756 arg1 profiles 758:765 the expression profiles 743:765 the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) 743:815 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 11 52 theme new 1918:1920 arg1 option 1922:1927 a new option 1916:1927 a new option for O-GlcNAcylation-based therapeutics in IDD prevention 1916:1984 These findings may provide a new option for O-GlcNAcylation-based therapeutics in IDD prevention. 36056188 5 53 theme nucleus 888:894 arg1 cells 910:914 nutrient-deprived nucleus pulposus (NP) cells 870:914 nutrient-deprived nucleus pulposus (NP) cells 870:914 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 4 54 theme ER-phagy 674:681 arg1 mechanisms 710:719 the related underlying mechanisms 687:719 the related underlying mechanisms in IDD 687:726 In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. 36056188 4 54 theme ER-phagy 674:681 arg1 function 642:649 the function 638:649 the function of O-GlcNAcylation and ER-phagy 638:681 In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. 36056188 7 55 theme FAM134B 1299:1305 arg1 knockdown 1307:1315 FAM134B knockdown 1299:1315 FAM134B knockdown 1299:1315 Moreover, FAM134B-mediated ER-phagy activation was regulated by O-GlcNAcylation, and suppression of ER-phagy by FAM134B knockdown considerably counteracted the protective effects of amplified O-GlcNAcylation. 36056188 11 56 theme IDD 1971:1973 arg1 prevention 1975:1984 IDD prevention 1971:1984 IDD prevention 1971:1984 These findings may provide a new option for O-GlcNAcylation-based therapeutics in IDD prevention. 36056188 1 57 theme endoplasmic 168:178 arg1 ER-phagy 197:204 ER-phagy 197:204 ER-phagy 197:204 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 57 theme endoplasmic 168:178 arg1 reticulum-phagy 180:194 endoplasmic reticulum-phagy 168:194 endoplasmic reticulum-phagy (ER-phagy) 168:205 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 57 theme endoplasmic 168:178 arg1 mechanisms 260:269 well-characterized conserved adaptive regulatory mechanisms 211:269 well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions 211:358 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 1 57 theme endoplasmic 168:178 arg1 β-N-acetylglucosaminylation 118:144 O-linked β-N-acetylglucosaminylation 109:144 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 109:162 Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. 36056188 8 58 theme FAM134B 1516:1522 arg1 degradation 1548:1558 FAM134B ubiquitination-mediated degradation 1516:1558 FAM134B ubiquitination-mediated degradation 1516:1558 Mechanistically, FAM134B was determined to be a potential target of OGT, and O-GlcNAcylation of FAM134B notably reduced FAM134B ubiquitination-mediated degradation. 36056188 6 59 theme deprivation 1158:1168 arg1 conditions 1175:1184 nutrient deprivation (ND) conditions 1149:1184 nutrient deprivation (ND) conditions 1149:1184 By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. 36056188 5 60 theme O-GlcNAcylation 770:784 arg1 profiles 758:765 the expression profiles 743:765 the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) 743:815 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 11 61 theme O-GlcNAcylation-based 1933:1953 arg1 therapeutics 1955:1966 O-GlcNAcylation-based therapeutics 1933:1966 O-GlcNAcylation-based therapeutics in IDD prevention 1933:1984 These findings may provide a new option for O-GlcNAcylation-based therapeutics in IDD prevention. 36056188 8 62 theme OGT 1464:1466 arg1 target 1454:1459 a potential target 1442:1459 a potential target of OGT 1442:1466 Mechanistically, FAM134B was determined to be a potential target of OGT, and O-GlcNAcylation of FAM134B notably reduced FAM134B ubiquitination-mediated degradation. 36056188 8 62 theme OGT 1464:1466 arg1 FAM134B 1413:1419 FAM134B 1413:1419 FAM134B 1413:1419 Mechanistically, FAM134B was determined to be a potential target of OGT, and O-GlcNAcylation of FAM134B notably reduced FAM134B ubiquitination-mediated degradation. 36056188 3 63 theme degeneration 568:579 arg1 pathogenesis 532:543 the pathogenesis 528:543 the pathogenesis of intervertebral disc degeneration (IDD) 528:585 However, whether O-GlcNAcylation or ER-phagy is involved in the pathogenesis of intervertebral disc degeneration (IDD) is largely unknown. 36056188 9 64 theme IDD 1667:1669 arg1 model 1671:1675 a rat IDD model 1661:1675 a rat IDD model 1661:1675 Correspondingly, the protection conferred by modulating O-GlcNAcylation homeostasis was verified in a rat IDD model. 36056188 2 65 theme human 449:453 arg1 pathologies 455:465 human pathologies 449:465 human pathologies 449:465 Abnormalities in O-GlcNAcylation and ER-phagy have been documented in a wide variety of human pathologies. 36056188 2 66 from Abnormalities 361:373 arg1 ER-phagy 398:405 ER-phagy 398:405 ER-phagy 398:405 Abnormalities in O-GlcNAcylation and ER-phagy have been documented in a wide variety of human pathologies. 36056188 2 66 from Abnormalities 361:373 arg1 O-GlcNAcylation 378:392 O-GlcNAcylation 378:392 O-GlcNAcylation 378:392 Abnormalities in O-GlcNAcylation and ER-phagy have been documented in a wide variety of human pathologies. 36056188 4 67 theme underlying 699:708 arg1 mechanisms 710:719 the related underlying mechanisms 687:719 the related underlying mechanisms in IDD 687:726 In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. 36056188 0 68 theme FAM134B-mediated 77:92 arg1 ER-phagy 94:101 FAM134B-mediated ER-phagy 77:101 FAM134B-mediated ER-phagy 77:101 O-GlcNAc transferase regulates intervertebral disc degeneration by targeting FAM134B-mediated ER-phagy. 36056188 5 69 theme pulposus 896:903 arg1 cells 910:914 nutrient-deprived nucleus pulposus (NP) cells 870:914 nutrient-deprived nucleus pulposus (NP) cells 870:914 We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. 36056188 4 70 theme related 691:697 arg1 mechanisms 710:719 the related underlying mechanisms 687:719 the related underlying mechanisms in IDD 687:726 In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. 35020790 7 0 theme special 1116:1122 arg1 O-Search 1137:1144 O-Search 1137:1144 O-Search 1137:1144 In addition, a special search mode, O-Search, is integrated into MS-Decipher to identify O-glycopeptides for O-glycoproteomic analysis. 35020790 7 0 theme special 1116:1122 arg1 mode 1131:1134 a special search mode 1114:1134 a special search mode 1114:1134 In addition, a special search mode, O-Search, is integrated into MS-Decipher to identify O-glycopeptides for O-glycoproteomic analysis. 35020790 4 1 theme peptides 865:872 arg1 identification 847:860 the identification 843:860 the identification of peptides from MS data 843:885 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 15 2 from online 1971:1976 arg1 available 1943:1951 available 1943:1951 available 1943:1951 SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 35020790 11 3 theme Several 1562:1568 arg1 formats 1575:1581 Several file formats 1562:1581 Several file formats 1562:1581 Several file formats are available in the searching and validation steps. 35020790 9 4 theme O-glycopeptide-spectra 1443:1464 arg1 matches 1466:1472 O-glycopeptide-spectra matches 1443:1472 O-glycopeptide-spectra matches 1443:1472 A useful tool is provided in MS-Decipher for the visualization of O-glycopeptide-spectra matches. 35020790 8 5 theme more 1339:1342 arg1 matches 1368:1374 about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches 1310:1374 about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches 1310:1374 Compared with Mascot, MetaMorpheus and MSFragger, MS-Decipher can obtain about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches. 35020790 0 6 theme O-linked 110:117 arg1 glycopeptides 119:131 O-linked glycopeptides 110:131 O-linked glycopeptides 110:131 MS-Decipher: a user-friendly proteome database search software with an emphasis on deciphering the spectra of O-linked glycopeptides. 35020790 0 7 gly glycopeptides 119:131 arg2 glycopeptides 119:131 O-linked glycopeptides 110:131 O-linked glycopeptides 110:131 MS-Decipher: a user-friendly proteome database search software with an emphasis on deciphering the spectra of O-linked glycopeptides. 35020790 1 8 theme system 376:381 arg1 mechanism 352:360 the regulation mechanism 337:360 the regulation mechanism of the living system 337:381 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 1 9 theme crucial 200:206 arg1 step 208:211 a crucial step 198:211 a crucial step in proteomics analysis 198:234 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 1 9 theme crucial 200:206 arg1 MOTIVATION 134:143 MOTIVATION 134:143 MOTIVATION The interpretation of mass spectrometry (MS) data 134:193 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 4 10 theme MS 879:880 arg1 data 882:885 MS data 879:885 MS data 879:885 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 5 11 theme scoring 892:898 arg1 schemes 900:906 Two scoring schemes 888:906 Two scoring schemes 888:906 Two scoring schemes can be chosen for peptide-spectra matching. 35020790 4 12 theme proteomic 699:707 arg1 datasets 709:716 proteomic datasets 699:716 proteomic datasets 699:716 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 8 13 theme % 1321:1321 arg1 matches 1368:1374 about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches 1310:1374 about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches 1310:1374 Compared with Mascot, MetaMorpheus and MSFragger, MS-Decipher can obtain about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches. 35020790 1 14 theme modifications 282:294 arg1 vital 306:310 vital 306:310 vital 306:310 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 1 14 theme modifications 282:294 arg1 identification 245:258 the identification 241:258 the identification of post-translational modifications (PTMs) 241:301 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 7 15 theme O-glycoproteomic 1210:1225 arg1 analysis 1227:1234 O-glycoproteomic analysis 1210:1234 O-glycoproteomic analysis 1210:1234 In addition, a special search mode, O-Search, is integrated into MS-Decipher to identify O-glycopeptides for O-glycoproteomic analysis. 35020790 4 16 from identification 847:860 arg1 data 882:885 MS data 879:885 MS data 879:885 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 1 17 theme mass 167:170 arg1 MS 186:187 MS 186:187 MS 186:187 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 1 17 theme mass 167:170 arg1 spectrometry 172:183 mass spectrometry 167:183 mass spectrometry (MS) data 167:193 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 13 18 theme IMPLEMENTATION 1723:1736 arg1 MS-Decipher 1738:1748 IMPLEMENTATION MS-Decipher 1723:1748 IMPLEMENTATION MS-Decipher 1723:1748 AVAILABILITY AND IMPLEMENTATION MS-Decipher is freely available at https://github.com/DICP-1809/MS-Decipher for academic use. 35020790 7 19 gly O-glycopeptides 1190:1204 arg2 O-glycopeptides 1190:1204 O-glycopeptides 1190:1204 O-glycopeptides for O-glycoproteomic analysis 1190:1234 In addition, a special search mode, O-Search, is integrated into MS-Decipher to identify O-glycopeptides for O-glycoproteomic analysis. 35020790 8 20 theme % 1337:1337 arg1 matches 1368:1374 about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches 1310:1374 about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches 1310:1374 Compared with Mascot, MetaMorpheus and MSFragger, MS-Decipher can obtain about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches. 35020790 9 21 theme matches 1466:1472 arg1 visualization 1426:1438 the visualization 1422:1438 the visualization of O-glycopeptide-spectra matches 1422:1472 A useful tool is provided in MS-Decipher for the visualization of O-glycopeptide-spectra matches. 35020790 1 22 theme mechanism 352:360 arg1 understanding 320:332 the understanding 316:332 the understanding of the regulation mechanism of the living system 316:381 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 6 23 theme traditional 1060:1070 arg1 database 1072:1079 traditional database 1060:1079 traditional database searching software 1060:1098 It was found that MS-Decipher had the same sensitivity and confidence in peptide identification compared to traditional database searching software. 35020790 8 24 theme O-glycopeptide-spectrum 1344:1366 arg1 matches 1368:1374 about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches 1310:1374 about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches 1310:1374 Compared with Mascot, MetaMorpheus and MSFragger, MS-Decipher can obtain about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches. 35020790 3 25 from performance 578:588 arg1 datasets 608:615 glycoproteomic datasets 593:615 glycoproteomic datasets 593:615 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 10 26 theme user 1517:1520 arg1 interface 1522:1530 a user-friendly graphical user interface 1491:1530 a user-friendly graphical user interface 1491:1530 MS-Decipher has a user-friendly graphical user interface, making it easier to operate. 35020790 4 27 theme O-glycoproteomic 730:745 arg1 datasets 747:754 O-glycoproteomic datasets 730:754 O-glycoproteomic datasets 730:754 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 14 28 theme implementation 1845:1858 arg1 steps 1860:1864 detailed implementation steps 1836:1864 detailed implementation steps 1836:1864 For detailed implementation steps, please see the user guide. 35020790 6 29 theme peptide 1025:1031 arg1 identification 1033:1046 peptide identification 1025:1046 peptide identification 1025:1046 It was found that MS-Decipher had the same sensitivity and confidence in peptide identification compared to traditional database searching software. 35020790 2 30 theme ones 445:448 arg1 one 421:423 one 421:423 one 421:423 Among various PTMs, glycosylation is one of the most diverse ones. 35020790 2 30 theme ones 445:448 arg1 ones 445:448 the most diverse ones 428:448 the most diverse ones 428:448 Among various PTMs, glycosylation is one of the most diverse ones. 35020790 10 31 theme user-friendly 1493:1505 arg1 interface 1522:1530 a user-friendly graphical user interface 1491:1530 a user-friendly graphical user interface 1491:1530 MS-Decipher has a user-friendly graphical user interface, making it easier to operate. 35020790 4 32 theme database 800:807 arg1 MS-Decipher 826:836 MS-Decipher 826:836 MS-Decipher 826:836 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 4 32 theme database 800:807 arg1 platform 816:823 a user-friendly proteomic database search platform 774:823 a user-friendly proteomic database search platform 774:823 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 2 33 theme various 390:396 arg1 PTMs 398:401 various PTMs 390:401 various PTMs 390:401 Among various PTMs, glycosylation is one of the most diverse ones. 35020790 0 34 theme proteome 29:36 arg1 search 47:52 a user-friendly proteome database search 13:52 MS-Decipher: a user-friendly proteome database search 0:52 MS-Decipher: a user-friendly proteome database search software with an emphasis on deciphering the spectra of O-linked glycopeptides. 35020790 3 35 theme glycoproteomic 593:606 arg1 datasets 608:615 glycoproteomic datasets 593:615 glycoproteomic datasets 593:615 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 11 36 theme searching 1604:1612 arg1 steps 1629:1633 the searching and validation steps 1600:1633 the searching and validation steps 1600:1633 Several file formats are available in the searching and validation steps. 35020790 3 37 theme many 458:461 arg1 engines 470:476 many search engines 458:476 many search engines 458:476 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 15 38 theme SUPPLEMENTARY 1894:1906 arg1 data 1934:1937 SUPPLEMENTARY INFORMATION Supplementary data 1894:1937 SUPPLEMENTARY INFORMATION Supplementary data 1894:1937 SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 35020790 3 39 theme advanced 629:636 arg1 software 653:660 advanced glycoproteomic software 629:660 advanced glycoproteomic software 629:660 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 4 40 theme user-friendly 776:788 arg1 MS-Decipher 826:836 MS-Decipher 826:836 MS-Decipher 826:836 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 4 40 theme user-friendly 776:788 arg1 platform 816:823 a user-friendly proteomic database search platform 774:823 a user-friendly proteomic database search platform 774:823 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 1 41 theme proteomics 216:225 arg1 analysis 227:234 proteomics analysis 216:234 proteomics analysis 216:234 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 0 42 dep MS-Decipher 0:10 arg1 search 47:52 a user-friendly proteome database search 13:52 MS-Decipher: a user-friendly proteome database search 0:52 MS-Decipher: a user-friendly proteome database search software with an emphasis on deciphering the spectra of O-linked glycopeptides. 35020790 11 43 theme validation 1618:1627 arg1 steps 1629:1633 the searching and validation steps 1600:1633 the searching and validation steps 1600:1633 Several file formats are available in the searching and validation steps. 35020790 13 44 theme academic 1818:1825 arg1 use 1827:1829 academic use 1818:1829 academic use 1818:1829 AVAILABILITY AND IMPLEMENTATION MS-Decipher is freely available at https://github.com/DICP-1809/MS-Decipher for academic use. 35020790 3 45 theme proteomic 510:518 arg1 data 520:523 proteomic data 510:523 proteomic data 510:523 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 1 46 theme spectrometry 172:183 arg1 data 190:193 mass spectrometry (MS) data 167:193 mass spectrometry (MS) data 167:193 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 6 47 from confidence 1011:1020 arg1 identification 1033:1046 peptide identification 1025:1046 peptide identification 1025:1046 It was found that MS-Decipher had the same sensitivity and confidence in peptide identification compared to traditional database searching software. 35020790 11 48 from steps 1629:1633 arg1 available 1587:1595 available 1587:1595 available 1587:1595 Several file formats are available in the searching and validation steps. 35020790 0 49 theme glycopeptides 119:131 arg1 spectra 99:105 the spectra 95:105 the spectra of O-linked glycopeptides 95:131 MS-Decipher: a user-friendly proteome database search software with an emphasis on deciphering the spectra of O-linked glycopeptides. 35020790 11 50 theme file 1570:1573 arg1 formats 1575:1581 Several file formats 1562:1581 Several file formats 1562:1581 Several file formats are available in the searching and validation steps. 35020790 1 51 theme data 190:193 arg1 interpretation 149:162 The interpretation 145:162 MOTIVATION The interpretation of mass spectrometry (MS) data 134:193 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 1 52 theme living 369:374 arg1 system 376:381 the living system 365:381 the living system 365:381 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 15 53 theme Supplementary 1920:1932 arg1 data 1934:1937 SUPPLEMENTARY INFORMATION Supplementary data 1894:1937 SUPPLEMENTARY INFORMATION Supplementary data 1894:1937 SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 35020790 1 54 from step 208:211 arg1 analysis 227:234 proteomics analysis 216:234 proteomics analysis 216:234 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 4 55 from data 882:885 arg1 identification 847:860 the identification 843:860 the identification of peptides from MS data 843:885 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 4 55 from data 882:885 arg1 peptides 865:872 peptides 865:872 peptides from MS data 865:885 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 3 56 theme poor 573:576 arg1 performance 578:588 poor performance 573:588 poor performance on glycoproteomic datasets compared to advanced glycoproteomic software 573:660 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 11 57 from available 1587:1595 arg1 steps 1629:1633 the searching and validation steps 1600:1633 the searching and validation steps 1600:1633 Several file formats are available in the searching and validation steps. 35020790 14 58 theme user 1882:1885 arg1 guide 1887:1891 the user guide 1878:1891 the user guide 1878:1891 For detailed implementation steps, please see the user guide. 35020790 6 59 theme same 990:993 arg1 sensitivity 995:1005 the same sensitivity 986:1005 the same sensitivity 986:1005 It was found that MS-Decipher had the same sensitivity and confidence in peptide identification compared to traditional database searching software. 35020790 15 60 theme Bioinformatics 1956:1969 arg1 online 1971:1976 Bioinformatics online 1956:1976 Bioinformatics online 1956:1976 SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 35020790 10 61 dep it 1540:1541 arg1 easier 1543:1548 easier 1543:1548 easier to operate 1543:1559 MS-Decipher has a user-friendly graphical user interface, making it easier to operate. 35020790 12 62 used used 1685:1688 arg2 MS-Decipher 1636:1646 MS-Decipher 1636:1646 MS-Decipher 1636:1646 MS-Decipher is implemented with Java, and can be used cross-platform. 35020790 13 63 dep https 1773:1777 arg1 //github.com/DICP-1809/MS-Decipher 1779:1812 //github.com/DICP-1809/MS-Decipher 1779:1812 https://github.com/DICP-1809/MS-Decipher for academic use 1773:1829 AVAILABILITY AND IMPLEMENTATION MS-Decipher is freely available at https://github.com/DICP-1809/MS-Decipher for academic use. 35020790 6 64 from sensitivity 995:1005 arg1 identification 1033:1046 peptide identification 1025:1046 peptide identification 1025:1046 It was found that MS-Decipher had the same sensitivity and confidence in peptide identification compared to traditional database searching software. 35020790 1 65 dep MOTIVATION 134:143 arg1 interpretation 149:162 The interpretation 145:162 MOTIVATION The interpretation of mass spectrometry (MS) data 134:193 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 1 66 theme regulation 341:350 arg1 mechanism 352:360 the regulation mechanism 337:360 the regulation mechanism of the living system 337:381 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 0 67 link O-linked 110:117 arg1 glycopeptides 119:131 O-linked glycopeptides 110:131 O-linked glycopeptides 110:131 MS-Decipher: a user-friendly proteome database search software with an emphasis on deciphering the spectra of O-linked glycopeptides. 35020790 4 68 theme datasets 709:716 arg1 analysis 687:694 the analysis 683:694 the analysis of proteomic datasets 683:716 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 0 69 theme user-friendly 15:27 arg1 search 47:52 a user-friendly proteome database search 13:52 MS-Decipher: a user-friendly proteome database search 0:52 MS-Decipher: a user-friendly proteome database search software with an emphasis on deciphering the spectra of O-linked glycopeptides. 35020790 1 70 theme post-translational 263:280 arg1 modifications 282:294 post-translational modifications 263:294 post-translational modifications (PTMs) 263:301 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 1 70 theme post-translational 263:280 arg1 PTMs 297:300 PTMs 297:300 PTMs 297:300 MOTIVATION The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. 35020790 10 71 theme graphical 1507:1515 arg1 interface 1522:1530 a user-friendly graphical user interface 1491:1530 a user-friendly graphical user interface 1491:1530 MS-Decipher has a user-friendly graphical user interface, making it easier to operate. 35020790 6 72 contain had 982:984 arg1 MS-Decipher 970:980 MS-Decipher 970:980 MS-Decipher 970:980 It was found that MS-Decipher had the same sensitivity and confidence in peptide identification compared to traditional database searching software. 35020790 6 72 contain had 982:984 arg2 confidence 1011:1020 confidence 1011:1020 confidence in peptide identification 1011:1046 It was found that MS-Decipher had the same sensitivity and confidence in peptide identification compared to traditional database searching software. 35020790 6 72 contain had 982:984 arg2 sensitivity 995:1005 the same sensitivity 986:1005 the same sensitivity 986:1005 It was found that MS-Decipher had the same sensitivity and confidence in peptide identification compared to traditional database searching software. 35020790 0 73 theme database 38:45 arg1 search 47:52 a user-friendly proteome database search 13:52 MS-Decipher: a user-friendly proteome database search 0:52 MS-Decipher: a user-friendly proteome database search software with an emphasis on deciphering the spectra of O-linked glycopeptides. 35020790 14 74 theme detailed 1836:1843 arg1 steps 1860:1864 detailed implementation steps 1836:1864 detailed implementation steps 1836:1864 For detailed implementation steps, please see the user guide. 35020790 2 75 theme diverse 437:443 arg1 ones 445:448 the most diverse ones 428:448 the most diverse ones 428:448 Among various PTMs, glycosylation is one of the most diverse ones. 35020790 4 76 theme proteomic 790:798 arg1 MS-Decipher 826:836 MS-Decipher 826:836 MS-Decipher 826:836 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 4 76 theme proteomic 790:798 arg1 platform 816:823 a user-friendly proteomic database search platform 774:823 a user-friendly proteomic database search platform 774:823 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 7 77 theme search 1124:1129 arg1 O-Search 1137:1144 O-Search 1137:1144 O-Search 1137:1144 In addition, a special search mode, O-Search, is integrated into MS-Decipher to identify O-glycopeptides for O-glycoproteomic analysis. 35020790 7 77 theme search 1124:1129 arg1 mode 1131:1134 a special search mode 1114:1134 a special search mode 1114:1134 In addition, a special search mode, O-Search, is integrated into MS-Decipher to identify O-glycopeptides for O-glycoproteomic analysis. 35020790 13 78 from https 1773:1777 arg1 available 1760:1768 available 1760:1768 available 1760:1768 AVAILABILITY AND IMPLEMENTATION MS-Decipher is freely available at https://github.com/DICP-1809/MS-Decipher for academic use. 35020790 3 79 theme glycoproteomic 638:651 arg1 software 653:660 advanced glycoproteomic software 629:660 advanced glycoproteomic software 629:660 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 4 80 theme search 809:814 arg1 MS-Decipher 826:836 MS-Decipher 826:836 MS-Decipher 826:836 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 4 80 theme search 809:814 arg1 platform 816:823 a user-friendly proteomic database search platform 774:823 a user-friendly proteomic database search platform 774:823 RESULTS To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. 35020790 3 81 theme search 463:468 arg1 engines 470:476 many search engines 458:476 many search engines 458:476 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 3 82 contain have 568:571 arg2 performance 578:588 poor performance 573:588 poor performance on glycoproteomic datasets compared to advanced glycoproteomic software 573:660 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 3 82 contain have 568:571 arg1 some 526:529 some 526:529 some 526:529 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 3 82 contain have 568:571 arg1 them 534:537 them 534:537 them 534:537 Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. 35020790 8 83 theme % 1328:1328 arg1 matches 1368:1374 about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches 1310:1374 about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches 1310:1374 Compared with Mascot, MetaMorpheus and MSFragger, MS-Decipher can obtain about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches. 35020790 9 84 theme useful 1379:1384 arg1 tool 1386:1389 A useful tool 1377:1389 A useful tool 1377:1389 A useful tool is provided in MS-Decipher for the visualization of O-glycopeptide-spectra matches. 35020790 10 85 contain has 1487:1489 arg1 MS-Decipher 1475:1485 MS-Decipher 1475:1485 MS-Decipher 1475:1485 MS-Decipher has a user-friendly graphical user interface, making it easier to operate. 35020790 10 85 contain has 1487:1489 arg2 interface 1522:1530 a user-friendly graphical user interface 1491:1530 a user-friendly graphical user interface 1491:1530 MS-Decipher has a user-friendly graphical user interface, making it easier to operate. 35020790 15 86 theme INFORMATION 1908:1918 arg1 data 1934:1937 SUPPLEMENTARY INFORMATION Supplementary data 1894:1937 SUPPLEMENTARY INFORMATION Supplementary data 1894:1937 SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. 33430751 7 0 theme dysfunction 1566:1576 arg1 onset 1532:1536 the onset 1528:1536 the onset of diabetes- induced visual dysfunction in mice 1528:1584 Remarkably, 4E-BP1/2 ablation delays the onset of diabetes- induced visual dysfunction in mice. 33430751 8 1 from impact 1638:1643 arg1 4E-BP1 1667:1672 4E-BP1 1667:1672 4E-BP1 1667:1672 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 3 2 theme protein 567:573 arg1 sensors 609:615 nutrient sensors 600:615 nutrient sensors 600:615 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 3 2 theme protein 567:573 arg1 flux 547:550 HBP flux 543:550 HBP flux 543:550 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 3 2 theme protein 567:573 arg1 O-GlcNAcylation 575:589 subsequent protein O-GlcNAcylation 556:589 subsequent protein O-GlcNAcylation 556:589 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 1 3 theme augmented 270:278 arg1 flux 280:283 augmented flux 270:283 augmented flux through the Hexosamine Biosynthetic Pathway (HBP) 270:333 It is well established that diabetes and its associated hyperglycemia negatively impact retinal function, yet we know little about the role played by augmented flux through the Hexosamine Biosynthetic Pathway (HBP). 33430751 7 4 theme induced 1551:1557 arg1 dysfunction 1566:1576 diabetes- induced visual dysfunction 1541:1576 diabetes- induced visual dysfunction in mice 1541:1584 Remarkably, 4E-BP1/2 ablation delays the onset of diabetes- induced visual dysfunction in mice. 33430751 4 5 theme mRNA 907:910 arg1 translation 912:922 mRNA translation 907:922 mRNA translation 907:922 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 6 6 theme O-GlcNAcylation-induced 1239:1261 arg1 changes 1263:1269 O-GlcNAcylation-induced changes 1239:1269 O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF) 1239:1352 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 8 7 theme retinal 1820:1826 arg1 O-GlcNAcylation 1828:1842 retinal O-GlcNAcylation 1820:1842 retinal O-GlcNAcylation 1820:1842 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 7 8 from onset 1532:1536 arg1 mice 1581:1584 mice 1581:1584 mice 1581:1584 Remarkably, 4E-BP1/2 ablation delays the onset of diabetes- induced visual dysfunction in mice. 33430751 8 9 from progression 1742:1752 arg1 regard 1769:1774 this regard 1764:1774 this regard 1764:1774 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 6 10 theme Growth 1333:1338 arg1 VEGF 1348:1351 VEGF 1348:1351 VEGF 1348:1351 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 10 theme Growth 1333:1338 arg1 Factor 1340:1345 Vascular Endothelial Growth Factor 1312:1345 Vascular Endothelial Growth Factor (VEGF) 1312:1352 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 3 11 theme nutrient 600:607 arg1 sensors 609:615 nutrient sensors 600:615 nutrient sensors 600:615 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 3 11 theme nutrient 600:607 arg1 flux 547:550 HBP flux 543:550 HBP flux 543:550 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 3 11 theme nutrient 600:607 arg1 O-GlcNAcylation 575:589 subsequent protein O-GlcNAcylation 556:589 subsequent protein O-GlcNAcylation 556:589 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 1 12 theme retinal 208:214 arg1 function 216:223 retinal function 208:223 retinal function 208:223 It is well established that diabetes and its associated hyperglycemia negatively impact retinal function, yet we know little about the role played by augmented flux through the Hexosamine Biosynthetic Pathway (HBP). 33430751 6 13 theme critical 1211:1218 arg1 role 1220:1223 a critical role 1209:1223 a critical role 1209:1223 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 8 14 theme ocular 1852:1857 arg1 system 1877:1882 the ocular renin-angiotensin system 1848:1882 the ocular renin-angiotensin system 1848:1882 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 0 15 from Cross-roads 83:93 arg1 Retinopathy 107:117 Diabetic Retinopathy 98:117 Diabetic Retinopathy 98:117 Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy. 33430751 6 16 theme Endothelial 1321:1331 arg1 VEGF 1348:1351 VEGF 1348:1351 VEGF 1348:1351 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 16 theme Endothelial 1321:1331 arg1 Factor 1340:1345 Vascular Endothelial Growth Factor 1312:1345 Vascular Endothelial Growth Factor (VEGF) 1312:1352 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 5 17 theme translational 1132:1144 arg1 4E-BP1 1156:1161 the translational repressor 4E-BP1 1128:1161 the translational repressor 4E-BP1 1128:1161 Augmented O-GlcNAcylation results in wide variation in the selection of mRNAs for translation, in part, due to O-GlcNAcylation of the translational repressor 4E-BP1. 33430751 4 18 from variation 894:902 arg1 translation 912:922 mRNA translation 907:922 mRNA translation 907:922 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 6 19 theme mitochondrial 1377:1389 arg1 proteins 1391:1398 important mitochondrial proteins 1367:1398 important mitochondrial proteins 1367:1398 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 4 20 theme Retinopathy 980:990 arg1 pathogenesis 955:966 the pathogenesis 951:966 the pathogenesis of Diabetic Retinopathy (DR) 951:995 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 4 20 theme Retinopathy 980:990 arg1 role 861:864 the role 857:864 the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction 857:945 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 8 21 from development 1726:1736 arg1 regard 1769:1774 this regard 1764:1774 this regard 1764:1774 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 4 22 from role 861:864 arg1 translation 912:922 mRNA translation 907:922 mRNA translation 907:922 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 4 22 from role 861:864 arg1 dysfunction 935:945 retinal dysfunction 927:945 retinal dysfunction 927:945 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 6 23 theme diabetes-induced 1452:1467 arg1 inflammation 1477:1488 diabetes-induced retinal inflammation 1452:1488 diabetes-induced retinal inflammation 1452:1488 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 8 24 theme interventions 1928:1940 arg1 target 1911:1916 a potential therapeutic target 1887:1916 a potential therapeutic target of future interventions 1887:1940 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 8 24 theme interventions 1928:1940 arg1 interplay 1802:1810 the potential interplay 1788:1810 the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system 1788:1882 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 1 25 theme associated 165:174 arg1 hyperglycemia 176:188 its associated hyperglycemia 161:188 its associated hyperglycemia 161:188 It is well established that diabetes and its associated hyperglycemia negatively impact retinal function, yet we know little about the role played by augmented flux through the Hexosamine Biosynthetic Pathway (HBP). 33430751 0 26 theme Diabetic 98:105 arg1 Retinopathy 107:117 Diabetic Retinopathy 98:117 Diabetic Retinopathy 98:117 Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy. 33430751 5 27 theme 4E-BP1 1156:1161 arg1 O-GlcNAcylation 1109:1123 O-GlcNAcylation 1109:1123 O-GlcNAcylation of the translational repressor 4E-BP1 1109:1161 Augmented O-GlcNAcylation results in wide variation in the selection of mRNAs for translation, in part, due to O-GlcNAcylation of the translational repressor 4E-BP1. 33430751 2 28 from modification 473:484 arg1 process 503:509 a process 501:509 a process referred to as O-GlcNAcylation 501:540 This offshoot of the glycolytic pathway produces UDP-Nacetyl- glucosamine, which serves as the substrate for post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation. 33430751 2 29 theme O-linked 464:471 arg1 modification 473:484 post-translational O-linked modification 445:484 post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation 445:540 This offshoot of the glycolytic pathway produces UDP-Nacetyl- glucosamine, which serves as the substrate for post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation. 33430751 1 30 theme Hexosamine 297:306 arg1 Pathway 321:327 the Hexosamine Biosynthetic Pathway 293:327 the Hexosamine Biosynthetic Pathway (HBP) 293:333 It is well established that diabetes and its associated hyperglycemia negatively impact retinal function, yet we know little about the role played by augmented flux through the Hexosamine Biosynthetic Pathway (HBP). 33430751 1 30 theme Hexosamine 297:306 arg1 HBP 330:332 HBP 330:332 HBP 330:332 It is well established that diabetes and its associated hyperglycemia negatively impact retinal function, yet we know little about the role played by augmented flux through the Hexosamine Biosynthetic Pathway (HBP). 33430751 0 31 theme Signaling 73:81 arg1 Cross-roads 83:93 Signaling Cross-roads 73:93 Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy. 0:118 Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy. 33430751 6 32 from changes 1263:1269 arg1 translation 1278:1288 the translation 1274:1288 the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF) 1274:1352 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 2 33 theme UDP-Nacetyl- 385:396 arg1 glucosamine 398:408 UDP-Nacetyl- glucosamine 385:408 UDP-Nacetyl- glucosamine 385:408 This offshoot of the glycolytic pathway produces UDP-Nacetyl- glucosamine, which serves as the substrate for post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation. 33430751 2 33 theme UDP-Nacetyl- 385:396 arg1 substrate 431:439 the substrate 427:439 the substrate for post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation 427:540 This offshoot of the glycolytic pathway produces UDP-Nacetyl- glucosamine, which serves as the substrate for post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation. 33430751 0 34 theme Retinal 0:6 arg1 O-GlcNAcylation 16:30 Retinal Protein O-GlcNAcylation 0:30 Retinal Protein O-GlcNAcylation 0:30 Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy. 33430751 7 35 theme 4E-BP1/2 1503:1510 arg1 ablation 1512:1519 4E-BP1/2 ablation 1503:1519 4E-BP1/2 ablation 1503:1519 Remarkably, 4E-BP1/2 ablation delays the onset of diabetes- induced visual dysfunction in mice. 33430751 8 36 theme O-GlcNAcylation 1648:1662 arg1 impact 1638:1643 the impact 1634:1643 the impact of O-GlcNAcylation on 4E-BP1 1634:1672 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 3 37 theme fundamental 694:704 arg1 processes 715:723 fundamental cellular processes 694:723 fundamental cellular processes 694:723 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 4 38 theme O-GlcNAcylation- 869:884 arg1 variation 894:902 O-GlcNAcylation- induced variation 869:902 O-GlcNAcylation- induced variation in mRNA translation 869:922 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 1 39 theme Biosynthetic 308:319 arg1 Pathway 321:327 the Hexosamine Biosynthetic Pathway 293:327 the Hexosamine Biosynthetic Pathway (HBP) 293:333 It is well established that diabetes and its associated hyperglycemia negatively impact retinal function, yet we know little about the role played by augmented flux through the Hexosamine Biosynthetic Pathway (HBP). 33430751 1 39 theme Biosynthetic 308:319 arg1 HBP 330:332 HBP 330:332 HBP 330:332 It is well established that diabetes and its associated hyperglycemia negatively impact retinal function, yet we know little about the role played by augmented flux through the Hexosamine Biosynthetic Pathway (HBP). 33430751 4 40 theme variation 894:902 arg1 pathogenesis 955:966 the pathogenesis 951:966 the pathogenesis of Diabetic Retinopathy (DR) 951:995 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 4 40 theme variation 894:902 arg1 role 861:864 the role 857:864 the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction 857:945 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 0 41 theme Renin-angiotensin 47:63 arg1 System 65:70 the Ocular Renin-angiotensin System 36:70 the Ocular Renin-angiotensin System 36:70 Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy. 33430751 3 42 theme gene 735:738 arg1 expression 740:749 gene expression 735:749 gene expression 735:749 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 4 43 from impact 774:779 arg1 physiology 804:813 retinal physiology 796:813 retinal physiology 796:813 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 0 44 dep O-GlcNAcylation 16:30 arg1 Cross-roads 83:93 Signaling Cross-roads 73:93 Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy. 0:118 Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy. 33430751 2 45 theme pathway 368:374 arg1 offshoot 341:348 This offshoot 336:348 This offshoot of the glycolytic pathway 336:374 This offshoot of the glycolytic pathway produces UDP-Nacetyl- glucosamine, which serves as the substrate for post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation. 33430751 6 46 from number 1357:1362 arg1 translation 1278:1288 the translation 1274:1288 the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF) 1274:1352 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 47 theme Recent 1164:1169 arg1 studies 1171:1177 Recent studies 1164:1177 Recent studies 1164:1177 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 7 48 theme visual 1559:1564 arg1 dysfunction 1566:1576 diabetes- induced visual dysfunction 1541:1576 diabetes- induced visual dysfunction in mice 1541:1584 Remarkably, 4E-BP1/2 ablation delays the onset of diabetes- induced visual dysfunction in mice. 33430751 4 49 theme retinal 927:933 arg1 dysfunction 935:945 retinal dysfunction 927:945 retinal dysfunction 927:945 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 3 50 theme subsequent 556:565 arg1 sensors 609:615 nutrient sensors 600:615 nutrient sensors 600:615 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 3 50 theme subsequent 556:565 arg1 flux 547:550 HBP flux 543:550 HBP flux 543:550 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 3 50 theme subsequent 556:565 arg1 O-GlcNAcylation 575:589 subsequent protein O-GlcNAcylation 556:589 subsequent protein O-GlcNAcylation 556:589 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 5 51 from variation 1040:1048 arg1 selection 1057:1065 the selection 1053:1065 the selection of mRNAs for translation 1053:1090 Augmented O-GlcNAcylation results in wide variation in the selection of mRNAs for translation, in part, due to O-GlcNAcylation of the translational repressor 4E-BP1. 33430751 7 52 theme diabetes- 1541:1549 arg1 dysfunction 1566:1576 diabetes- induced visual dysfunction 1541:1576 diabetes- induced visual dysfunction in mice 1541:1584 Remarkably, 4E-BP1/2 ablation delays the onset of diabetes- induced visual dysfunction in mice. 33430751 8 53 theme potential 1792:1800 arg1 target 1911:1916 a potential therapeutic target 1887:1916 a potential therapeutic target of future interventions 1887:1940 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 8 53 theme potential 1792:1800 arg1 interplay 1802:1810 the potential interplay 1788:1810 the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system 1788:1882 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 7 54 from dysfunction 1566:1576 arg1 mice 1581:1584 mice 1581:1584 mice 1581:1584 Remarkably, 4E-BP1/2 ablation delays the onset of diabetes- induced visual dysfunction in mice. 33430751 6 55 theme Vascular 1312:1319 arg1 VEGF 1348:1351 VEGF 1348:1351 VEGF 1348:1351 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 55 theme Vascular 1312:1319 arg1 Factor 1340:1345 Vascular Endothelial Growth Factor 1312:1345 Vascular Endothelial Growth Factor (VEGF) 1312:1352 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 56 theme proteins 1391:1398 arg1 CD40 1405:1408 CD40 1405:1408 CD40 1405:1408 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 56 theme proteins 1391:1398 arg1 molecule 1431:1438 a key costimulatory molecule 1411:1438 a key costimulatory molecule involved in diabetes-induced retinal inflammation 1411:1488 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 56 theme proteins 1391:1398 arg1 changes 1263:1269 O-GlcNAcylation-induced changes 1239:1269 O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF) 1239:1352 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 56 theme proteins 1391:1398 arg1 number 1357:1362 a number 1355:1362 a number of important mitochondrial proteins 1355:1398 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 5 57 theme repressor 1146:1154 arg1 4E-BP1 1156:1161 the translational repressor 4E-BP1 1128:1161 the translational repressor 4E-BP1 1128:1161 Augmented O-GlcNAcylation results in wide variation in the selection of mRNAs for translation, in part, due to O-GlcNAcylation of the translational repressor 4E-BP1. 33430751 8 58 theme renin-angiotensin 1859:1875 arg1 system 1877:1882 the ocular renin-angiotensin system 1848:1882 the ocular renin-angiotensin system 1848:1882 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 7 59 from mice 1581:1584 arg1 onset 1532:1536 the onset 1528:1536 the onset of diabetes- induced visual dysfunction in mice 1528:1584 Remarkably, 4E-BP1/2 ablation delays the onset of diabetes- induced visual dysfunction in mice. 33430751 6 60 theme mRNAs 1297:1301 arg1 translation 1278:1288 the translation 1274:1288 the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF) 1274:1352 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 61 theme important 1367:1375 arg1 proteins 1391:1398 important mitochondrial proteins 1367:1398 important mitochondrial proteins 1367:1398 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 3 62 theme metabolic 646:654 arg1 information 656:666 metabolic information 646:666 metabolic information 646:666 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 4 63 theme Diabetic 971:978 arg1 DR 993:994 DR 993:994 DR 993:994 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 4 63 theme Diabetic 971:978 arg1 Retinopathy 980:990 Diabetic Retinopathy 971:990 Diabetic Retinopathy (DR) 971:995 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 6 64 theme retinal 1469:1475 arg1 inflammation 1477:1488 diabetes-induced retinal inflammation 1452:1488 diabetes-induced retinal inflammation 1452:1488 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 4 65 from pathogenesis 955:966 arg1 translation 912:922 mRNA translation 907:922 mRNA translation 907:922 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 4 65 from pathogenesis 955:966 arg1 dysfunction 935:945 retinal dysfunction 927:945 retinal dysfunction 927:945 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 8 66 theme potential 1889:1897 arg1 target 1911:1916 a potential therapeutic target 1887:1916 a potential therapeutic target of future interventions 1887:1940 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 8 66 theme potential 1889:1897 arg1 interplay 1802:1810 the potential interplay 1788:1810 the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system 1788:1882 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 8 67 theme DR. 1757:1759 arg1 progression 1742:1752 progression 1742:1752 progression 1742:1752 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 8 67 theme DR. 1757:1759 arg1 development 1726:1736 development 1726:1736 development 1726:1736 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 6 68 theme costimulatory 1417:1429 arg1 molecule 1431:1438 a key costimulatory molecule 1411:1438 a key costimulatory molecule involved in diabetes-induced retinal inflammation 1411:1488 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 68 theme costimulatory 1417:1429 arg1 CD40 1405:1408 CD40 1405:1408 CD40 1405:1408 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 8 69 theme pharmacological 1593:1607 arg1 interventions 1609:1621 pharmacological interventions 1593:1621 pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 1593:1672 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 8 70 dep development 1726:1736 arg1 the 1722:1724 the 1722:1724 the 1722:1724 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 8 71 theme future 1921:1926 arg1 interventions 1928:1940 future interventions 1921:1940 future interventions 1921:1940 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 5 72 theme wide 1035:1038 arg1 variation 1040:1048 wide variation 1035:1048 wide variation in the selection of mRNAs for translation 1035:1090 Augmented O-GlcNAcylation results in wide variation in the selection of mRNAs for translation, in part, due to O-GlcNAcylation of the translational repressor 4E-BP1. 33430751 2 73 link O-linked 464:471 arg1 modification 473:484 post-translational O-linked modification 445:484 post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation 445:540 This offshoot of the glycolytic pathway produces UDP-Nacetyl- glucosamine, which serves as the substrate for post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation. 33430751 6 74 theme key 1413:1415 arg1 molecule 1431:1438 a key costimulatory molecule 1411:1438 a key costimulatory molecule involved in diabetes-induced retinal inflammation 1411:1488 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 6 74 theme key 1413:1415 arg1 CD40 1405:1408 CD40 1405:1408 CD40 1405:1408 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 4 75 from translation 912:922 arg1 pathogenesis 955:966 the pathogenesis 951:966 the pathogenesis of Diabetic Retinopathy (DR) 951:995 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 4 75 from translation 912:922 arg1 role 861:864 the role 857:864 the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction 857:945 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 4 76 theme recent 829:834 arg1 studies 836:842 recent studies 829:842 recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR) 829:995 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 0 77 theme Protein 8:14 arg1 O-GlcNAcylation 16:30 Retinal Protein O-GlcNAcylation 0:30 Retinal Protein O-GlcNAcylation 0:30 Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy. 33430751 8 78 dep therapeutics 1698:1709 arg1 discuss 1780:1786 discuss 1780:1786 discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions 1780:1940 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 5 79 theme Augmented 998:1006 arg1 O-GlcNAcylation 1008:1022 Augmented O-GlcNAcylation 998:1022 Augmented O-GlcNAcylation 998:1022 Augmented O-GlcNAcylation results in wide variation in the selection of mRNAs for translation, in part, due to O-GlcNAcylation of the translational repressor 4E-BP1. 33430751 2 80 theme post-translational 445:462 arg1 modification 473:484 post-translational O-linked modification 445:484 post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation 445:540 This offshoot of the glycolytic pathway produces UDP-Nacetyl- glucosamine, which serves as the substrate for post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation. 33430751 4 81 theme diabetes 784:791 arg1 impact 774:779 the impact 770:779 the impact of diabetes on retinal physiology 770:813 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 4 82 theme retinal 796:802 arg1 physiology 804:813 retinal physiology 796:813 retinal physiology 796:813 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 0 83 theme Ocular 40:45 arg1 System 65:70 the Ocular Renin-angiotensin System 36:70 the Ocular Renin-angiotensin System 36:70 Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy. 33430751 6 84 from CD40 1405:1408 arg1 translation 1278:1288 the translation 1274:1288 the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF) 1274:1352 Recent studies demonstrate that 4E-BP1 plays a critical role in regulating O-GlcNAcylation-induced changes in the translation of the mRNAs encoding Vascular Endothelial Growth Factor (VEGF), a number of important mitochondrial proteins, and CD40, a key costimulatory molecule involved in diabetes-induced retinal inflammation. 33430751 2 85 theme proteins 489:496 arg1 modification 473:484 post-translational O-linked modification 445:484 post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation 445:540 This offshoot of the glycolytic pathway produces UDP-Nacetyl- glucosamine, which serves as the substrate for post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation. 33430751 8 86 theme promising 1688:1696 arg1 therapeutics 1698:1709 promising therapeutics 1688:1709 promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions 1688:1940 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 4 87 theme induced 886:892 arg1 variation 894:902 O-GlcNAcylation- induced variation 869:902 O-GlcNAcylation- induced variation in mRNA translation 869:922 Here we summarize the impact of diabetes on retinal physiology, highlighting recent studies that explore the role of O-GlcNAcylation- induced variation in mRNA translation in retinal dysfunction and the pathogenesis of Diabetic Retinopathy (DR). 33430751 3 88 theme cellular 706:713 arg1 processes 715:723 fundamental cellular processes 694:723 fundamental cellular processes 694:723 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 2 89 theme glycolytic 357:366 arg1 pathway 368:374 the glycolytic pathway 353:374 the glycolytic pathway 353:374 This offshoot of the glycolytic pathway produces UDP-Nacetyl- glucosamine, which serves as the substrate for post-translational O-linked modification of proteins in a process referred to as O-GlcNAcylation. 33430751 5 90 theme mRNAs 1070:1074 arg1 selection 1057:1065 the selection 1053:1065 the selection of mRNAs for translation 1053:1090 Augmented O-GlcNAcylation results in wide variation in the selection of mRNAs for translation, in part, due to O-GlcNAcylation of the translational repressor 4E-BP1. 33430751 8 91 dep potential 1889:1897 arg1 therapeutic 1899:1909 therapeutic 1899:1909 therapeutic 1899:1909 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 33430751 3 92 theme HBP 543:545 arg1 flux 547:550 HBP flux 543:550 HBP flux 543:550 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 3 92 theme HBP 543:545 arg1 sensors 609:615 nutrient sensors 600:615 nutrient sensors 600:615 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 3 92 theme HBP 543:545 arg1 O-GlcNAcylation 575:589 subsequent protein O-GlcNAcylation 556:589 subsequent protein O-GlcNAcylation 556:589 HBP flux and subsequent protein O-GlcNAcylation serve as nutrient sensors, enabling cells to integrate metabolic information to appropriately modulate fundamental cellular processes including gene expression. 33430751 8 93 dep interventions 1609:1621 arg1 prevent 1626:1632 prevent 1626:1632 to prevent the impact of O-GlcNAcylation on 4E-BP1 1623:1672 Thus, pharmacological interventions to prevent the impact of O-GlcNAcylation on 4E-BP1 may represent promising therapeutics to address the development and progression of DR. In this regard, we discuss the potential interplay between retinal O-GlcNAcylation and the ocular renin-angiotensin system as a potential therapeutic target of future interventions. 35980012 0 0 theme IgG 83:85 arg1 Reactivity 96:105 IgG Antibody Reactivity 83:105 IgG Antibody Reactivity 83:105 Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity. 35980012 3 1 theme embryonic 475:483 arg1 kidney 485:490 human embryonic kidney 469:490 human embryonic kidney cells 469:496 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 6 2 theme fucose 1000:1005 arg1 content 1007:1013 reduced fucose content 992:1013 reduced fucose content 992:1013 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 4 3 from carbohydrates 572:584 arg1 proteins 597:604 the RBD proteins 589:604 the RBD proteins 589:604 The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. 35980012 0 4 from Acid 7:10 arg1 Domain 67:72 the SARS-CoV-2 Receptor-Binding Domain 35:72 the SARS-CoV-2 Receptor-Binding Domain 35:72 Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity. 35980012 1 5 theme SARS-CoV-2 149:158 arg1 protein 166:172 the SARS-CoV-2 spike protein 145:172 the SARS-CoV-2 spike protein 145:172 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 6 6 theme reduced 992:998 arg1 content 1007:1013 reduced fucose content 992:1013 reduced fucose content 992:1013 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 3 7 theme N-linked 377:384 arg1 glycans 386:392 complex-type N-linked glycans 364:392 complex-type N-linked glycans 364:392 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 3 8 theme same 514:517 arg1 protein 519:525 the same protein 510:525 the same protein produced in Chinese hamster ovary cells 510:565 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 2 9 theme recombinant 281:291 arg1 RBD 293:295 the recombinant RBD 277:295 the recombinant RBD produced in different mammalian cells 277:333 We defined the carbohydrate content of the recombinant RBD produced in different mammalian cells. 35980012 3 10 theme glycans 386:392 arg1 degree 354:359 a higher degree 345:359 a higher degree of complex-type N-linked glycans 345:392 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 0 11 theme Antibody 87:94 arg1 Reactivity 96:105 IgG Antibody Reactivity 83:105 IgG Antibody Reactivity 83:105 Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity. 35980012 6 12 with devoid 960:965 arg1 content 1007:1013 reduced fucose content 992:1013 reduced fucose content 992:1013 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 6 13 theme monosaccharides 1099:1113 arg1 importance 1070:1079 the importance 1066:1079 the importance of these specific monosaccharides 1066:1113 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 4 14 from effect 644:649 arg1 reactivity 663:672 antibody reactivity 654:672 antibody reactivity 654:672 The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. 35980012 4 15 theme serum 693:697 arg1 samples 699:705 serum samples 693:705 serum samples from SARS-CoV-2 positive patients 693:739 The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. 35980012 4 16 theme SARS-CoV-2 712:721 arg1 patients 732:739 SARS-CoV-2 positive patients 712:739 SARS-CoV-2 positive patients 712:739 The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. 35980012 1 17 theme spike 160:164 arg1 protein 166:172 the SARS-CoV-2 spike protein 145:172 the SARS-CoV-2 spike protein 145:172 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 4 18 from patients 732:739 arg1 samples 699:705 serum samples 693:705 serum samples from SARS-CoV-2 positive patients 693:739 The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. 35980012 2 19 theme carbohydrate 253:264 arg1 content 266:272 the carbohydrate content 249:272 the carbohydrate content of the recombinant RBD produced in different mammalian cells 249:333 We defined the carbohydrate content of the recombinant RBD produced in different mammalian cells. 35980012 6 20 theme specific 1090:1097 arg1 monosaccharides 1099:1113 these specific monosaccharides 1084:1113 these specific monosaccharides 1084:1113 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 1 21 theme protein 166:172 arg1 domain 189:194 a conserved domain 177:194 a conserved domain 177:194 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 1 21 theme protein 166:172 arg1 RBD 137:139 RBD 137:139 RBD 137:139 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 1 21 theme protein 166:172 arg1 domain 129:134 The receptor-binding domain 108:134 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein 108:172 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 1 21 theme protein 166:172 arg1 protein 166:172 the SARS-CoV-2 spike protein 145:172 the SARS-CoV-2 spike protein 145:172 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 3 22 theme complex-type 364:375 arg1 glycans 386:392 complex-type N-linked glycans 364:392 complex-type N-linked glycans 364:392 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 0 23 from Residues 23:30 arg1 Domain 67:72 the SARS-CoV-2 Receptor-Binding Domain 35:72 the SARS-CoV-2 Receptor-Binding Domain 35:72 Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity. 35980012 3 24 theme Chinese 539:545 arg1 cells 561:565 Chinese hamster ovary cells 539:565 Chinese hamster ovary cells 539:565 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 7 25 theme proteins 1276:1283 arg1 immunogenicity 1240:1253 the immunogenicity 1236:1253 the immunogenicity of recombinant viral proteins 1236:1283 The results can be of importance for the design of future vaccine candidates, indicating that it is possible to enhance the immunogenicity of recombinant viral proteins. 35980012 0 26 theme Sialic 0:5 arg1 Acid 7:10 Sialic Acid and Fucose Residues 0:30 Acid 7:10 Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity. 35980012 6 27 theme acids 977:981 arg1 devoid 960:965 devoid 960:965 devoid 960:965 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 3 28 theme hamster 547:553 arg1 cells 561:565 Chinese hamster ovary cells 539:565 Chinese hamster ovary cells 539:565 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 0 29 theme Fucose 16:21 arg1 Residues 23:30 Sialic Acid and Fucose Residues 0:30 Residues 23:30 Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity. 35980012 6 30 theme sialic 970:975 arg1 acids 977:981 sialic acids 970:981 sialic acids 970:981 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 2 31 theme RBD 293:295 arg1 content 266:272 the carbohydrate content 249:272 the carbohydrate content of the recombinant RBD produced in different mammalian cells 249:333 We defined the carbohydrate content of the recombinant RBD produced in different mammalian cells. 35980012 1 32 theme conserved 179:187 arg1 domain 189:194 a conserved domain 177:194 a conserved domain 177:194 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 1 32 theme conserved 179:187 arg1 domain 129:134 The receptor-binding domain 108:134 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein 108:172 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 1 32 theme conserved 179:187 arg1 protein 166:172 the SARS-CoV-2 spike protein 145:172 the SARS-CoV-2 spike protein 145:172 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 7 33 theme future 1167:1172 arg1 candidates 1182:1191 future vaccine candidates 1167:1191 future vaccine candidates 1167:1191 The results can be of importance for the design of future vaccine candidates, indicating that it is possible to enhance the immunogenicity of recombinant viral proteins. 35980012 3 34 theme kidney 485:490 arg1 cells 492:496 human embryonic kidney cells 469:496 human embryonic kidney cells 469:496 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 5 35 theme sialic 825:830 arg1 acids 832:836 only sialic acids 820:836 only sialic acids 820:836 Removal of all carbohydrates diminished antibody reactivity, while removal of only sialic acids or terminal fucoses improved the reactivity. 35980012 5 36 theme carbohydrates 757:769 arg1 Removal 742:748 Removal 742:748 Removal of all carbohydrates 742:769 Removal of all carbohydrates diminished antibody reactivity, while removal of only sialic acids or terminal fucoses improved the reactivity. 35980012 6 37 theme devoid 960:965 arg1 structures 949:958 carbohydrate structures 936:958 carbohydrate structures devoid of sialic acids and with reduced fucose content 936:1013 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 7 38 theme candidates 1182:1191 arg1 design 1157:1162 the design 1153:1162 the design of future vaccine candidates 1153:1191 The results can be of importance for the design of future vaccine candidates, indicating that it is possible to enhance the immunogenicity of recombinant viral proteins. 35980012 5 39 theme acids 832:836 arg1 removal 809:815 removal 809:815 removal of only sialic acids or terminal fucoses 809:856 Removal of all carbohydrates diminished antibody reactivity, while removal of only sialic acids or terminal fucoses improved the reactivity. 35980012 5 40 theme terminal 841:848 arg1 fucoses 850:856 terminal fucoses 841:856 terminal fucoses 841:856 Removal of all carbohydrates diminished antibody reactivity, while removal of only sialic acids or terminal fucoses improved the reactivity. 35980012 4 41 theme RBD 593:595 arg1 proteins 597:604 the RBD proteins 589:604 the RBD proteins 589:604 The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. 35980012 6 42 theme antibody 1035:1042 arg1 reactivity 1044:1053 enhanced antibody reactivity 1026:1053 enhanced antibody reactivity 1026:1053 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 0 43 theme SARS-CoV-2 39:48 arg1 Domain 67:72 the SARS-CoV-2 Receptor-Binding Domain 35:72 the SARS-CoV-2 Receptor-Binding Domain 35:72 Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity. 35980012 6 44 theme carbohydrate 936:947 arg1 structures 949:958 carbohydrate structures 936:958 carbohydrate structures devoid of sialic acids and with reduced fucose content 936:1013 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 3 45 theme ovary 555:559 arg1 cells 561:565 Chinese hamster ovary cells 539:565 Chinese hamster ovary cells 539:565 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 1 46 theme receptor-binding 112:127 arg1 domain 189:194 a conserved domain 177:194 a conserved domain 177:194 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 1 46 theme receptor-binding 112:127 arg1 RBD 137:139 RBD 137:139 RBD 137:139 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 1 46 theme receptor-binding 112:127 arg1 domain 129:134 The receptor-binding domain 108:134 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein 108:172 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 1 46 theme receptor-binding 112:127 arg1 protein 166:172 the SARS-CoV-2 spike protein 145:172 the SARS-CoV-2 spike protein 145:172 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 3 47 theme human 469:473 arg1 kidney 485:490 human embryonic kidney 469:490 human embryonic kidney cells 469:496 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 7 48 theme recombinant 1258:1268 arg1 proteins 1276:1283 recombinant viral proteins 1258:1283 recombinant viral proteins 1258:1283 The results can be of importance for the design of future vaccine candidates, indicating that it is possible to enhance the immunogenicity of recombinant viral proteins. 35980012 5 49 theme antibody 782:789 arg1 reactivity 791:800 antibody reactivity 782:800 antibody reactivity 782:800 Removal of all carbohydrates diminished antibody reactivity, while removal of only sialic acids or terminal fucoses improved the reactivity. 35980012 2 50 theme mammalian 319:327 arg1 cells 329:333 different mammalian cells 309:333 different mammalian cells 309:333 We defined the carbohydrate content of the recombinant RBD produced in different mammalian cells. 35980012 6 51 theme enhanced 1026:1033 arg1 reactivity 1044:1053 enhanced antibody reactivity 1026:1053 enhanced antibody reactivity 1026:1053 The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. 35980012 4 52 theme positive 723:730 arg1 patients 732:739 SARS-CoV-2 positive patients 712:739 SARS-CoV-2 positive patients 712:739 The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. 35980012 2 53 theme different 309:317 arg1 cells 329:333 different mammalian cells 309:333 different mammalian cells 309:333 We defined the carbohydrate content of the recombinant RBD produced in different mammalian cells. 35980012 7 54 theme viral 1270:1274 arg1 proteins 1276:1283 recombinant viral proteins 1258:1283 recombinant viral proteins 1258:1283 The results can be of importance for the design of future vaccine candidates, indicating that it is possible to enhance the immunogenicity of recombinant viral proteins. 35980012 5 55 theme only 820:823 arg1 acids 832:836 only sialic acids 820:836 only sialic acids 820:836 Removal of all carbohydrates diminished antibody reactivity, while removal of only sialic acids or terminal fucoses improved the reactivity. 35980012 4 56 theme antibody 654:661 arg1 reactivity 663:672 antibody reactivity 654:672 antibody reactivity 654:672 The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. 35980012 5 57 theme fucoses 850:856 arg1 removal 809:815 removal 809:815 removal of only sialic acids or terminal fucoses 809:856 Removal of all carbohydrates diminished antibody reactivity, while removal of only sialic acids or terminal fucoses improved the reactivity. 35980012 1 58 theme neutralizing 213:224 arg1 antibodies 226:235 neutralizing antibodies 213:235 neutralizing antibodies 213:235 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. 35980012 0 59 theme Receptor-Binding 50:65 arg1 Domain 67:72 the SARS-CoV-2 Receptor-Binding Domain 35:72 the SARS-CoV-2 Receptor-Binding Domain 35:72 Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity. 35980012 3 60 link N-linked 377:384 arg1 glycans 386:392 complex-type N-linked glycans 364:392 complex-type N-linked glycans 364:392 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35980012 7 61 theme vaccine 1174:1180 arg1 candidates 1182:1191 future vaccine candidates 1167:1191 future vaccine candidates 1167:1191 The results can be of importance for the design of future vaccine candidates, indicating that it is possible to enhance the immunogenicity of recombinant viral proteins. 35980012 3 62 theme higher 347:352 arg1 degree 354:359 a higher degree 345:359 a higher degree of complex-type N-linked glycans 345:392 We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. 35332324 0 0 theme lysosomal 96:104 arg1 phosphorylation 120:134 lysosomal enzyme glycan phosphorylation 96:134 lysosomal enzyme glycan phosphorylation 96:134 Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation. 35332324 4 1 theme enzyme 691:696 arg1 activation 673:682 activation 673:682 activation of the enzyme 673:696 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 6 2 from enzyme 1103:1108 arg1 state 1124:1128 the active state 1113:1128 the active state 1113:1128 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 35332324 6 3 theme selective 991:999 arg1 binding 1011:1017 selective substrate binding 991:1017 selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase 991:1091 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 35332324 4 4 theme core 587:590 arg1 identification 615:628 the identification 611:628 the identification of a hockey stick-like motif that controls activation of the enzyme 611:696 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 4 4 theme core 587:590 arg1 structure 560:568 a cryo-EM structure 550:568 a cryo-EM structure of the catalytic core of human PTase 550:605 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 0 5 theme glycan 113:118 arg1 phosphorylation 120:134 lysosomal enzyme glycan phosphorylation 96:134 lysosomal enzyme glycan phosphorylation 96:134 Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation. 35332324 6 6 theme hydrolase 1034:1042 arg1 binding 1011:1017 selective substrate binding 991:1017 selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase 991:1091 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 35332324 4 7 theme PTase 601:605 arg1 core 587:590 the catalytic core 573:590 the catalytic core of human PTase 573:605 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 0 8 theme enzyme 106:111 arg1 phosphorylation 120:134 lysosomal enzyme glycan phosphorylation 96:134 lysosomal enzyme glycan phosphorylation 96:134 Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation. 35332324 4 9 theme human 595:599 arg1 PTase 601:605 human PTase 595:605 human PTase 595:605 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 5 10 theme catalytic 733:741 arg1 pocket 743:748 the catalytic pocket 729:748 the catalytic pocket 729:748 Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. 35332324 5 11 theme hydrolase 833:841 arg1 access 850:855 hydrolase glycan access 833:855 hydrolase glycan access to the catalytic site 833:877 Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. 35332324 5 12 theme catalytic 864:872 arg1 site 874:877 the catalytic site 860:877 the catalytic site 860:877 Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. 35332324 1 13 theme -recognition 182:193 arg1 system 195:200 the mannose 6-phosphate (M6P)-recognition system 153:200 the mannose 6-phosphate (M6P)-recognition system 153:200 Vertebrates use the mannose 6-phosphate (M6P)-recognition system to deliver lysosomal hydrolases to lysosomes. 35332324 5 14 theme peripheral 800:809 arg1 domains 811:817 the peripheral domains 796:817 the peripheral domains 796:817 Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. 35332324 3 15 theme catalytic 453:461 arg1 core 463:466 a catalytic core 451:466 a catalytic core 451:466 Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. 35332324 2 16 theme hydrolases 395:404 arg1 hydrolases 395:404 hydrolases 395:404 hydrolases 395:404 Key to this pathway is N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases. 35332324 2 16 theme hydrolases 395:404 arg1 residues 383:390 mannose residues 375:390 mannose residues of hydrolases 375:404 Key to this pathway is N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases. 35332324 3 17 theme Human 407:411 arg1 heterohexamer 432:444 an α2β2γ2 heterohexamer 422:444 an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates 422:532 Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. 35332324 3 17 theme Human 407:411 arg1 PTase 413:417 Human PTase 407:417 Human PTase 407:417 Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. 35332324 6 18 theme protein-binding 1056:1070 arg1 determinant 1072:1082 its protein-binding determinant 1052:1082 its protein-binding determinant 1052:1082 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 35332324 0 19 theme human 17:21 arg1 subunits 54:61 the human GlcNAc-1-phosphotransferase αβ subunits 13:61 the human GlcNAc-1-phosphotransferase αβ subunits 13:61 Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation. 35332324 6 20 theme active 960:965 arg1 states 967:972 inactive and active states 947:972 inactive and active states in solution 947:984 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 35332324 6 21 theme glycan 1140:1145 arg1 phosphorylation 1147:1161 glycan phosphorylation 1140:1161 glycan phosphorylation 1140:1161 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 35332324 3 22 theme several 472:478 arg1 domains 491:497 several peripheral domains 472:497 several peripheral domains 472:497 Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. 35332324 4 23 theme catalytic 577:585 arg1 core 587:590 the catalytic core 573:590 the catalytic core of human PTase 573:605 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 3 24 theme peripheral 480:489 arg1 domains 491:497 several peripheral domains 472:497 several peripheral domains 472:497 Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. 35332324 0 25 theme αβ 51:52 arg1 subunits 54:61 the human GlcNAc-1-phosphotransferase αβ subunits 13:61 the human GlcNAc-1-phosphotransferase αβ subunits 13:61 Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation. 35332324 5 26 theme motif 716:720 arg1 Movement 699:706 Movement 699:706 Movement of this motif out of the catalytic pocket 699:748 Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. 35332324 5 27 theme glycan 843:848 arg1 access 850:855 hydrolase glycan access 833:855 hydrolase glycan access to the catalytic site 833:877 Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. 35332324 4 28 theme motif 653:657 arg1 identification 615:628 the identification 611:628 the identification of a hockey stick-like motif that controls activation of the enzyme 611:696 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 4 28 theme motif 653:657 arg1 structure 560:568 a cryo-EM structure 550:568 a cryo-EM structure of the catalytic core of human PTase 550:605 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 0 29 theme GlcNAc-1-phosphotransferase 23:49 arg1 subunits 54:61 the human GlcNAc-1-phosphotransferase αβ subunits 13:61 the human GlcNAc-1-phosphotransferase αβ subunits 13:61 Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation. 35332324 6 30 theme inactive 947:954 arg1 states 967:972 inactive and active states 947:972 inactive and active states in solution 947:984 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 35332324 3 31 theme α2β2γ2 425:430 arg1 heterohexamer 432:444 an α2β2γ2 heterohexamer 422:444 an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates 422:532 Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. 35332324 3 31 theme α2β2γ2 425:430 arg1 PTase 413:417 Human PTase 407:417 Human PTase 407:417 Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. 35332324 5 32 theme domains 811:817 arg1 part 788:791 part 788:791 part of the peripheral domains 788:817 Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. 35332324 6 33 from states 967:972 arg1 solution 977:984 solution 977:984 solution 977:984 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 35332324 4 34 theme stick-like 642:651 arg1 motif 653:657 a hockey stick-like motif 633:657 a hockey stick-like motif that controls activation of the enzyme 633:696 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 5 35 theme part 788:791 arg1 rearrangement 771:783 a rearrangement 769:783 a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase 769:903 Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. 35332324 3 36 with heterohexamer 432:444 arg1 domains 491:497 several peripheral domains 472:497 several peripheral domains 472:497 Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. 35332324 3 36 with heterohexamer 432:444 arg1 core 463:466 a catalytic core 451:466 a catalytic core 451:466 Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. 35332324 7 37 theme enzymes 1237:1243 arg1 glycans 1216:1222 only N-linked glycans 1202:1222 only N-linked glycans of lysosomal enzymes 1202:1243 This mechanism would help ensure that only N-linked glycans of lysosomal enzymes are phosphorylated. 35332324 0 38 theme subunits 54:61 arg1 Structure 0:8 Structure 0:8 Structure of the human GlcNAc-1-phosphotransferase αβ subunits 0:61 Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation. 35332324 4 39 theme cryo-EM 552:558 arg1 structure 560:568 a cryo-EM structure 550:568 a cryo-EM structure of the catalytic core of human PTase 550:605 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 7 40 theme N-linked 1207:1214 arg1 glycans 1216:1222 only N-linked glycans 1202:1222 only N-linked glycans of lysosomal enzymes 1202:1243 This mechanism would help ensure that only N-linked glycans of lysosomal enzymes are phosphorylated. 35332324 6 41 theme active 1117:1122 arg1 state 1124:1128 the active state 1113:1128 the active state 1113:1128 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 35332324 7 42 link N-linked 1207:1214 arg1 glycans 1216:1222 only N-linked glycans 1202:1222 only N-linked glycans of lysosomal enzymes 1202:1243 This mechanism would help ensure that only N-linked glycans of lysosomal enzymes are phosphorylated. 35332324 2 43 theme N-acetylglucosamine 271:289 arg1 -1-phosphotransferase 299:319 N-acetylglucosamine (GlcNAc)-1-phosphotransferase 271:319 N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases 271:404 Key to this pathway is N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases. 35332324 2 43 theme N-acetylglucosamine 271:289 arg1 PTase 322:326 PTase 322:326 PTase 322:326 Key to this pathway is N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases. 35332324 1 44 theme mannose 157:163 arg1 M6P 178:180 M6P 178:180 M6P 178:180 Vertebrates use the mannose 6-phosphate (M6P)-recognition system to deliver lysosomal hydrolases to lysosomes. 35332324 1 44 theme mannose 157:163 arg1 6-phosphate 165:175 mannose 6-phosphate 157:175 the mannose 6-phosphate (M6P)-recognition system 153:200 Vertebrates use the mannose 6-phosphate (M6P)-recognition system to deliver lysosomal hydrolases to lysosomes. 35332324 7 45 theme lysosomal 1227:1235 arg1 enzymes 1237:1243 lysosomal enzymes 1227:1243 lysosomal enzymes 1227:1243 This mechanism would help ensure that only N-linked glycans of lysosomal enzymes are phosphorylated. 35332324 6 46 theme lysosomal 1024:1032 arg1 hydrolase 1034:1042 a lysosomal hydrolase 1022:1042 a lysosomal hydrolase through its protein-binding determinant 1022:1082 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 35332324 1 47 theme lysosomal 213:221 arg1 hydrolases 223:232 lysosomal hydrolases 213:232 lysosomal hydrolases to lysosomes 213:245 Vertebrates use the mannose 6-phosphate (M6P)-recognition system to deliver lysosomal hydrolases to lysosomes. 35332324 1 48 theme 6-phosphate 165:175 arg1 system 195:200 the mannose 6-phosphate (M6P)-recognition system 153:200 the mannose 6-phosphate (M6P)-recognition system 153:200 Vertebrates use the mannose 6-phosphate (M6P)-recognition system to deliver lysosomal hydrolases to lysosomes. 35332324 0 49 theme regulatory 71:80 arg1 mechanism 82:90 regulatory mechanism 71:90 regulatory mechanism for lysosomal enzyme glycan phosphorylation 71:134 Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation. 35332324 4 50 theme hockey 635:640 arg1 motif 653:657 a hockey stick-like motif 633:657 a hockey stick-like motif that controls activation of the enzyme 633:696 Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. 35332324 2 51 theme mannose 375:381 arg1 hydrolases 395:404 hydrolases 395:404 hydrolases 395:404 Key to this pathway is N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases. 35332324 2 51 theme mannose 375:381 arg1 residues 383:390 mannose residues 375:390 mannose residues of hydrolases 375:404 Key to this pathway is N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases. 35332324 6 52 theme substrate 1001:1009 arg1 binding 1011:1017 selective substrate binding 991:1017 selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase 991:1091 We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. 37359538 10 0 from role 1781:1784 arg1 healing 1805:1811 wound healing 1799:1811 wound healing 1799:1811 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 8 1 theme molecular 1217:1225 arg1 fragments 1240:1248 cleaved low molecular weight FCGBP fragments 1205:1248 cleaved low molecular weight FCGBP fragments 1205:1248 FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. 37359538 7 2 theme mucus-associated 1078:1093 arg1 proteins 1095:1102 other mucus-associated proteins 1072:1102 other mucus-associated proteins 1072:1102 However, FCGBP interacted with other mucus-associated proteins. 37359538 9 3 theme enhanced 1367:1374 arg1 proliferation 1376:1388 enhanced proliferation 1367:1388 enhanced proliferation 1367:1388 In MUC2 KO, cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. 37359538 9 4 dep closure 1518:1524 arg1 margin 1491:1496 the wound margin 1481:1496 the wound margin which impeded wound closure by 6 days 1481:1534 In MUC2 KO, cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. 37359538 10 5 theme epithelial 1825:1834 arg1 function 1844:1851 epithelial barrier function 1825:1851 epithelial barrier function 1825:1851 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 6 theme novel 1753:1757 arg1 role 1781:1784 a potential novel endogenous protective role 1741:1784 a potential novel endogenous protective role for FCGBP in wound healing 1741:1811 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 7 from 15-days 1711:1717 arg1 increase 1646:1653 a rapid increase 1638:1653 a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS 1638:1726 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 7 from 15-days 1711:1717 arg1 mRNA 1664:1667 Fcgbp mRNA 1658:1667 Fcgbp mRNA 1658:1667 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 7 from 15-days 1711:1717 arg1 expression 1689:1698 delayed protein expression 1673:1698 delayed protein expression at 12- and 15-days post DSS 1673:1726 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 2 8 theme MUC2 332:335 arg1 mucin 337:341 MUC2 mucin 332:341 MUC2 mucin 332:341 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 2 8 theme MUC2 332:335 arg1 components 283:292 The major components 273:292 The major components of mucus secreted by goblet cells 273:326 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 4 9 theme MUC2 763:766 arg1 cells 771:775 CRISPR-Cas9 gene-edited MUC2 KO cells 739:775 CRISPR-Cas9 gene-edited MUC2 KO cells 739:775 MUC2 and FCGBP were coordinately regulated temporally in goblet-like cells and in response to a mucus secretagogue but not in CRISPR-Cas9 gene-edited MUC2 KO cells. 37359538 10 10 theme rapid 1640:1644 arg1 increase 1646:1653 a rapid increase 1638:1653 a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS 1638:1726 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 2 11 theme major 277:281 arg1 mucin 337:341 MUC2 mucin 332:341 MUC2 mucin 332:341 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 2 11 theme major 277:281 arg1 components 283:292 The major components 273:292 The major components of mucus secreted by goblet cells 273:326 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 10 12 from 12- 1703:1705 arg1 increase 1646:1653 a rapid increase 1638:1653 a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS 1638:1726 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 12 from 12- 1703:1705 arg1 mRNA 1664:1667 Fcgbp mRNA 1658:1667 Fcgbp mRNA 1658:1667 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 12 from 12- 1703:1705 arg1 expression 1689:1698 delayed protein expression 1673:1698 delayed protein expression at 12- and 15-days post DSS 1673:1726 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 13 theme DSS 1540:1542 arg1 colitis 1544:1550 DSS colitis 1540:1550 DSS colitis 1540:1550 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 9 14 theme WT 1431:1432 arg1 cells 1434:1438 WT cells 1431:1438 WT cells 1431:1438 In MUC2 KO, cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. 37359538 7 15 theme other 1072:1076 arg1 proteins 1095:1102 other mucus-associated proteins 1072:1102 other mucus-associated proteins 1072:1102 However, FCGBP interacted with other mucus-associated proteins. 37359538 5 16 theme cells 917:921 arg1 cytoplasm 892:900 the cytoplasm 888:900 the cytoplasm of goblet-like cells 888:921 Whereas ~85% of MUC2 was colocalized with FCGBP in mucin granules, ~50% of FCGBP was diffusely distributed in the cytoplasm of goblet-like cells. 37359538 3 17 from role 576:579 arg1 function 603:610 epithelial barrier function 584:610 epithelial barrier function 584:610 In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. 37359538 1 18 theme commensal 251:259 arg1 microbiota 261:270 the commensal microbiota 247:270 the commensal microbiota 247:270 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 0 19 theme wound 122:126 arg1 healing 128:134 wound healing 122:134 wound healing 122:134 IgGFc-binding protein and MUC2 mucin produced by colonic goblet-like cells spatially interact non-covalently and regulate wound healing. 37359538 5 20 theme FCGBP 853:857 arg1 % 848:848 ~50% 845:848 ~50% of FCGBP 845:857 Whereas ~85% of MUC2 was colocalized with FCGBP in mucin granules, ~50% of FCGBP was diffusely distributed in the cytoplasm of goblet-like cells. 37359538 5 20 theme FCGBP 853:857 arg1 FCGBP 853:857 FCGBP 853:857 FCGBP 853:857 Whereas ~85% of MUC2 was colocalized with FCGBP in mucin granules, ~50% of FCGBP was diffusely distributed in the cytoplasm of goblet-like cells. 37359538 8 21 theme FCGBP 1234:1238 arg1 fragments 1240:1248 cleaved low molecular weight FCGBP fragments 1205:1248 cleaved low molecular weight FCGBP fragments 1205:1248 FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. 37359538 4 22 theme gene-edited 751:761 arg1 cells 771:775 CRISPR-Cas9 gene-edited MUC2 KO cells 739:775 CRISPR-Cas9 gene-edited MUC2 KO cells 739:775 MUC2 and FCGBP were coordinately regulated temporally in goblet-like cells and in response to a mucus secretagogue but not in CRISPR-Cas9 gene-edited MUC2 KO cells. 37359538 8 23 theme weight 1227:1232 arg1 fragments 1240:1248 cleaved low molecular weight FCGBP fragments 1205:1248 cleaved low molecular weight FCGBP fragments 1205:1248 FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. 37359538 1 24 theme first 170:174 arg1 bilayer 155:161 The colonic mucus bilayer 137:161 The colonic mucus bilayer 137:161 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 1 24 theme first 170:174 arg1 line 176:179 the first line 166:179 the first line of innate host defense that at the same time houses and nourishes the commensal microbiota 166:270 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 6 25 theme v11 934:936 arg1 analysis 938:945 STRING-db v11 analysis 924:945 STRING-db v11 analysis of the mucin granule proteome 924:975 STRING-db v11 analysis of the mucin granule proteome revealed no protein-protein interaction between MUC2 and FCGBP. 37359538 10 26 theme Muc2 1600:1603 arg1 littermates 1605:1615 Muc2 but not Muc2 littermates 1587:1615 Muc2 but not Muc2 littermates 1587:1615 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 27 theme healed 1569:1574 arg1 lesions 1576:1582 healed lesions 1569:1582 healed lesions 1569:1582 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 28 from increase 1646:1653 arg1 15-days 1711:1717 15-days 1711:1717 15-days 1711:1717 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 28 from increase 1646:1653 arg1 12- 1703:1705 12- 1703:1705 12- 1703:1705 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 28 from increase 1646:1653 arg1 mRNA 1664:1667 Fcgbp mRNA 1658:1667 Fcgbp mRNA 1658:1667 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 28 from increase 1646:1653 arg1 expression 1689:1698 delayed protein expression 1673:1698 delayed protein expression at 12- and 15-days post DSS 1673:1726 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 4 29 theme CRISPR-Cas9 739:749 arg1 cells 771:775 CRISPR-Cas9 gene-edited MUC2 KO cells 739:775 CRISPR-Cas9 gene-edited MUC2 KO cells 739:775 MUC2 and FCGBP were coordinately regulated temporally in goblet-like cells and in response to a mucus secretagogue but not in CRISPR-Cas9 gene-edited MUC2 KO cells. 37359538 8 30 theme cleaved 1205:1211 arg1 fragments 1240:1248 cleaved low molecular weight FCGBP fragments 1205:1248 cleaved low molecular weight FCGBP fragments 1205:1248 FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. 37359538 10 31 theme protein 1681:1687 arg1 expression 1689:1698 delayed protein expression 1673:1698 delayed protein expression at 12- and 15-days post DSS 1673:1726 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 32 theme delayed 1673:1679 arg1 expression 1689:1698 delayed protein expression 1673:1698 delayed protein expression at 12- and 15-days post DSS 1673:1726 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 33 theme Fcgbp 1658:1662 arg1 mRNA 1664:1667 Fcgbp mRNA 1658:1667 Fcgbp mRNA 1658:1667 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 4 34 theme mucus 709:713 arg1 secretagogue 715:726 a mucus secretagogue 707:726 a mucus secretagogue 707:726 MUC2 and FCGBP were coordinately regulated temporally in goblet-like cells and in response to a mucus secretagogue but not in CRISPR-Cas9 gene-edited MUC2 KO cells. 37359538 5 35 theme mucin 829:833 arg1 granules 835:842 mucin granules 829:842 mucin granules 829:842 Whereas ~85% of MUC2 was colocalized with FCGBP in mucin granules, ~50% of FCGBP was diffusely distributed in the cytoplasm of goblet-like cells. 37359538 0 36 theme IgGFc-binding 0:12 arg1 protein 14:20 IgGFc-binding protein 0:20 IgGFc-binding protein 0:20 IgGFc-binding protein and MUC2 mucin produced by colonic goblet-like cells spatially interact non-covalently and regulate wound healing. 37359538 6 37 theme STRING-db 924:932 arg1 analysis 938:945 STRING-db v11 analysis 924:945 STRING-db v11 analysis of the mucin granule proteome 924:975 STRING-db v11 analysis of the mucin granule proteome revealed no protein-protein interaction between MUC2 and FCGBP. 37359538 2 38 theme mucus 297:301 arg1 mucin 337:341 MUC2 mucin 332:341 MUC2 mucin 332:341 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 2 38 theme mucus 297:301 arg1 components 283:292 The major components 273:292 The major components of mucus secreted by goblet cells 273:326 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 2 39 theme mucus-associated 351:366 arg1 FCGBP 377:381 FCGBP 377:381 FCGBP 377:381 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 2 39 theme mucus-associated 351:366 arg1 protein 398:404 IgGFc-binding protein 384:404 IgGFc-binding protein 384:404 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 2 39 theme mucus-associated 351:366 arg1 protein 368:374 the mucus-associated protein 347:374 the mucus-associated protein 347:374 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 0 40 theme MUC2 26:29 arg1 mucin 31:35 MUC2 mucin 26:35 MUC2 mucin 26:35 IgGFc-binding protein and MUC2 mucin produced by colonic goblet-like cells spatially interact non-covalently and regulate wound healing. 37359538 1 41 theme host 191:194 arg1 defense 196:202 innate host defense 184:202 innate host defense 184:202 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 8 42 link N-linked 1135:1142 arg1 glycans 1144:1150 N-linked glycans 1135:1150 N-linked glycans 1135:1150 FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. 37359538 9 43 theme impeded 1504:1510 arg1 closure 1518:1524 impeded wound closure 1504:1524 impeded wound closure by 6 days 1504:1534 In MUC2 KO, cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. 37359538 3 44 theme structural 529:538 arg1 integrity 540:548 the structural integrity 525:548 the structural integrity of secreted mucus 525:566 In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. 37359538 8 45 with mucus 1194:1198 arg1 fragments 1240:1248 cleaved low molecular weight FCGBP fragments 1205:1248 cleaved low molecular weight FCGBP fragments 1205:1248 FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. 37359538 1 46 theme defense 196:202 arg1 bilayer 155:161 The colonic mucus bilayer 137:161 The colonic mucus bilayer 137:161 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 1 46 theme defense 196:202 arg1 line 176:179 the first line 166:179 the first line of innate host defense that at the same time houses and nourishes the commensal microbiota 166:270 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 8 47 theme secreted 1185:1192 arg1 mucus 1194:1198 secreted mucus 1185:1198 secreted mucus with cleaved low molecular weight FCGBP fragments 1185:1248 FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. 37359538 5 48 theme goblet-like 905:915 arg1 cells 917:921 goblet-like cells 905:921 goblet-like cells 905:921 Whereas ~85% of MUC2 was colocalized with FCGBP in mucin granules, ~50% of FCGBP was diffusely distributed in the cytoplasm of goblet-like cells. 37359538 6 49 theme protein-protein 989:1003 arg1 interaction 1005:1015 no protein-protein interaction 986:1015 no protein-protein interaction between MUC2 and FCGBP 986:1038 STRING-db v11 analysis of the mucin granule proteome revealed no protein-protein interaction between MUC2 and FCGBP. 37359538 10 50 theme wound 1799:1803 arg1 healing 1805:1811 wound healing 1799:1811 wound healing 1799:1811 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 1 51 theme innate 184:189 arg1 defense 196:202 innate host defense 184:202 innate host defense 184:202 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 2 52 theme IgGFc-binding 384:396 arg1 protein 398:404 IgGFc-binding protein 384:404 IgGFc-binding protein 384:404 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 2 52 theme IgGFc-binding 384:396 arg1 protein 368:374 the mucus-associated protein 347:374 the mucus-associated protein 347:374 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 8 53 theme low 1213:1215 arg1 fragments 1240:1248 cleaved low molecular weight FCGBP fragments 1205:1248 cleaved low molecular weight FCGBP fragments 1205:1248 FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. 37359538 9 54 theme wounded 1338:1344 arg1 cells 1346:1350 wounded cells 1338:1350 wounded cells that healed by enhanced proliferation and migration within 2 days 1338:1416 In MUC2 KO, cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. 37359538 10 55 theme protective 1770:1779 arg1 role 1781:1784 a potential novel endogenous protective role 1741:1784 a potential novel endogenous protective role for FCGBP in wound healing 1741:1811 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 8 56 theme N-linked 1135:1142 arg1 glycans 1144:1150 N-linked glycans 1135:1150 N-linked glycans 1135:1150 FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. 37359538 0 57 theme colonic 49:55 arg1 cells 69:73 colonic goblet-like cells 49:73 colonic goblet-like cells 49:73 IgGFc-binding protein and MUC2 mucin produced by colonic goblet-like cells spatially interact non-covalently and regulate wound healing. 37359538 10 58 theme potential 1743:1751 arg1 role 1781:1784 a potential novel endogenous protective role 1741:1784 a potential novel endogenous protective role for FCGBP in wound healing 1741:1811 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 10 59 theme endogenous 1759:1768 arg1 role 1781:1784 a potential novel endogenous protective role 1741:1784 a potential novel endogenous protective role for FCGBP in wound healing 1741:1811 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 3 60 theme secreted 553:560 arg1 mucus 562:566 secreted mucus 553:566 secreted mucus 553:566 In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. 37359538 3 61 theme MUC2 449:452 arg1 mucin 454:458 MUC2 mucin 449:458 MUC2 mucin 449:458 In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. 37359538 9 62 theme cytoplasmic 1263:1273 arg1 FCGBP 1275:1279 cytoplasmic FCGBP 1263:1279 cytoplasmic FCGBP 1263:1279 In MUC2 KO, cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. 37359538 9 63 theme wound 1485:1489 arg1 margin 1491:1496 the wound margin 1481:1496 the wound margin which impeded wound closure by 6 days 1481:1534 In MUC2 KO, cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. 37359538 10 64 theme barrier 1836:1842 arg1 function 1844:1851 epithelial barrier function 1825:1851 epithelial barrier function 1825:1851 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 3 65 theme mucus 562:566 arg1 integrity 540:548 the structural integrity 525:548 the structural integrity of secreted mucus 525:566 In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. 37359538 3 65 theme mucus 562:566 arg1 role 576:579 its role 572:579 its role in epithelial barrier function 572:610 In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. 37359538 4 66 theme KO 768:769 arg1 cells 771:775 CRISPR-Cas9 gene-edited MUC2 KO cells 739:775 CRISPR-Cas9 gene-edited MUC2 KO cells 739:775 MUC2 and FCGBP were coordinately regulated temporally in goblet-like cells and in response to a mucus secretagogue but not in CRISPR-Cas9 gene-edited MUC2 KO cells. 37359538 3 67 theme epithelial 584:593 arg1 function 603:610 epithelial barrier function 584:610 epithelial barrier function 584:610 In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. 37359538 6 68 theme proteome 968:975 arg1 analysis 938:945 STRING-db v11 analysis 924:945 STRING-db v11 analysis of the mucin granule proteome 924:975 STRING-db v11 analysis of the mucin granule proteome revealed no protein-protein interaction between MUC2 and FCGBP. 37359538 2 69 theme goblet 315:320 arg1 cells 322:326 goblet cells 315:326 goblet cells 315:326 The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). 37359538 4 70 theme goblet-like 670:680 arg1 cells 682:686 goblet-like cells 670:686 goblet-like cells 670:686 MUC2 and FCGBP were coordinately regulated temporally in goblet-like cells and in response to a mucus secretagogue but not in CRISPR-Cas9 gene-edited MUC2 KO cells. 37359538 9 71 theme wound 1512:1516 arg1 closure 1518:1524 impeded wound closure 1504:1524 impeded wound closure by 6 days 1504:1534 In MUC2 KO, cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. 37359538 3 72 theme barrier 595:601 arg1 function 603:610 epithelial barrier function 584:610 epithelial barrier function 584:610 In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. 37359538 1 73 theme colonic 141:147 arg1 bilayer 155:161 The colonic mucus bilayer 137:161 The colonic mucus bilayer 137:161 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 1 73 theme colonic 141:147 arg1 line 176:179 the first line 166:179 the first line of innate host defense that at the same time houses and nourishes the commensal microbiota 166:270 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 3 74 from integrity 540:548 arg1 function 603:610 epithelial barrier function 584:610 epithelial barrier function 584:610 In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. 37359538 1 75 theme same 216:219 arg1 time 221:224 the same time 212:224 the same time 212:224 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 5 76 theme MUC2 794:797 arg1 MUC2 794:797 MUC2 794:797 MUC2 794:797 Whereas ~85% of MUC2 was colocalized with FCGBP in mucin granules, ~50% of FCGBP was diffusely distributed in the cytoplasm of goblet-like cells. 37359538 5 76 theme MUC2 794:797 arg1 % 789:789 ~85% 786:789 ~85% of MUC2 786:797 Whereas ~85% of MUC2 was colocalized with FCGBP in mucin granules, ~50% of FCGBP was diffusely distributed in the cytoplasm of goblet-like cells. 37359538 1 77 theme mucus 149:153 arg1 bilayer 155:161 The colonic mucus bilayer 137:161 The colonic mucus bilayer 137:161 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 1 77 theme mucus 149:153 arg1 line 176:179 the first line 166:179 the first line of innate host defense that at the same time houses and nourishes the commensal microbiota 166:270 The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. 37359538 10 78 theme Muc2 1587:1590 arg1 littermates 1605:1615 Muc2 but not Muc2 littermates 1587:1615 Muc2 but not Muc2 littermates 1587:1615 In DSS colitis, restitution and healed lesions in Muc2 but not Muc2 littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function. 37359538 6 79 theme granule 960:966 arg1 proteome 968:975 the mucin granule proteome 950:975 the mucin granule proteome 950:975 STRING-db v11 analysis of the mucin granule proteome revealed no protein-protein interaction between MUC2 and FCGBP. 37359538 0 80 theme goblet-like 57:67 arg1 cells 69:73 colonic goblet-like cells 49:73 colonic goblet-like cells 49:73 IgGFc-binding protein and MUC2 mucin produced by colonic goblet-like cells spatially interact non-covalently and regulate wound healing. 37359538 9 81 theme MUC2 1254:1257 arg1 KO 1259:1260 MUC2 KO 1254:1260 MUC2 KO 1254:1260 In MUC2 KO, cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. 37359538 6 82 theme mucin 954:958 arg1 proteome 968:975 the mucin granule proteome 950:975 the mucin granule proteome 950:975 STRING-db v11 analysis of the mucin granule proteome revealed no protein-protein interaction between MUC2 and FCGBP. 36945111 7 0 theme IgG 1507:1509 arg1 subclasses 1511:1520 all IgG subclasses 1503:1520 all IgG subclasses 1503:1520 Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. 36945111 6 1 theme hamster 1080:1086 arg1 productivity 1099:1110 Chinese hamster ovary cell productivity 1072:1110 Chinese hamster ovary cell productivity 1072:1110 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 5 2 from impact 932:937 arg1 stability 999:1007 high concentration stability 980:1007 high concentration stability 980:1007 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 2 from impact 932:937 arg1 manufacturability 958:974 manufacturability 958:974 manufacturability 958:974 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 3 with IgG1 783:786 arg1 functions 830:838 diminished effector functions 810:838 diminished effector functions 810:838 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 3 with IgG1 783:786 arg1 interaction 903:913 further reduced FcγR interaction 882:913 further reduced FcγR interaction 882:913 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 2 4 theme IgG 275:277 arg1 subclasses 279:288 the IgG subclasses 271:288 the IgG subclasses 271:288 Multiple laboratories have reported that the IgG subclasses possess different molecular characteristics that can affect their developability. 36945111 6 5 from concentration 1240:1252 arg1 change 1315:1320 charge variant profile change 1292:1320 charge variant profile change 1292:1320 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 5 from concentration 1240:1252 arg1 fragmentation 1277:1289 fragmentation 1277:1289 fragmentation 1277:1289 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 5 from concentration 1240:1252 arg1 structure 1167:1175 N-linked glycan structure 1151:1175 N-linked glycan structure at the conserved N297 Fc position 1151:1209 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 5 from concentration 1240:1252 arg1 modification 1346:1357 post-translational modification 1327:1357 post-translational modification 1327:1357 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 5 from concentration 1240:1252 arg1 appearance 1221:1230 solution appearance 1212:1230 solution appearance at high concentration 1212:1252 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 5 from concentration 1240:1252 arg1 efficiency 1139:1148 host cell protein removal efficiency 1113:1148 host cell protein removal efficiency 1113:1148 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 5 from concentration 1240:1252 arg1 growth 1269:1274 aggregate growth 1259:1274 aggregate growth 1259:1274 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 5 from concentration 1240:1252 arg1 productivity 1099:1110 Chinese hamster ovary cell productivity 1072:1110 Chinese hamster ovary cell productivity 1072:1110 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 6 theme glycan 1160:1165 arg1 structure 1167:1175 N-linked glycan structure 1151:1175 N-linked glycan structure at the conserved N297 Fc position 1151:1209 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 1 7 theme related 158:164 arg1 variants 166:173 related variants 158:173 related variants 158:173 IgG-based monoclonal antibody therapeutics, which are mainly IgG1, IgG2, and IgG4 subclasses or related variants, have dominated the biotherapeutics field for decades. 36945111 5 8 with variant 797:803 arg1 functions 830:838 diminished effector functions 810:838 diminished effector functions 810:838 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 8 with variant 797:803 arg1 interaction 903:913 further reduced FcγR interaction 882:913 further reduced FcγR interaction 882:913 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 9 theme systematic 683:692 arg1 study 694:698 a systematic study 681:698 a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, 681:914 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 2 10 theme molecular 308:316 arg1 characteristics 318:332 different molecular characteristics 298:332 different molecular characteristics that can affect their developability 298:369 Multiple laboratories have reported that the IgG subclasses possess different molecular characteristics that can affect their developability. 36945111 8 11 theme balanced 1719:1726 arg1 decision 1728:1735 a balanced decision 1717:1735 a balanced decision on IgG subclass selection for therapeutic antibodies 1717:1788 These learnings can be used to enable a balanced decision on IgG subclass selection for therapeutic antibodies and aid in acceleration of their product development process. 36945111 6 12 theme removal 1131:1137 arg1 efficiency 1139:1148 host cell protein removal efficiency 1113:1148 host cell protein removal efficiency 1113:1148 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 5 13 theme mAbs 706:709 arg1 study 694:698 a systematic study 681:698 a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, 681:914 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 14 theme effector 821:828 arg1 functions 830:838 diminished effector functions 810:838 diminished effector functions 810:838 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 7 15 theme IgG 1621:1623 arg1 subclass 1625:1632 IgG subclass 1621:1632 IgG subclass 1621:1632 Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. 36945111 6 16 theme profile 1307:1313 arg1 change 1315:1320 charge variant profile change 1292:1320 charge variant profile change 1292:1320 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 8 17 theme subclass 1744:1751 arg1 selection 1753:1761 IgG subclass selection 1740:1761 IgG subclass selection 1740:1761 These learnings can be used to enable a balanced decision on IgG subclass selection for therapeutic antibodies and aid in acceleration of their product development process. 36945111 1 18 theme biotherapeutics 195:209 arg1 field 211:215 the biotherapeutics field 191:215 the biotherapeutics field for decades 191:227 IgG-based monoclonal antibody therapeutics, which are mainly IgG1, IgG2, and IgG4 subclasses or related variants, have dominated the biotherapeutics field for decades. 36945111 3 19 contain have 451:454 arg1 subclass 412:419 the most popular IgG subclass 391:419 the most popular IgG subclass for therapeutics 391:436 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 3 19 contain have 451:454 arg1 IgG1 385:388 IgG1 385:388 IgG1 385:388 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 3 19 contain have 451:454 arg2 pathway 485:491 a characteristic degradation pathway 456:491 a characteristic degradation pathway related to its hinge fragility 456:522 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 6 20 theme charge 1292:1297 arg1 change 1315:1320 charge variant profile change 1292:1320 charge variant profile change 1292:1320 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 5 21 theme common 1014:1019 arg1 matrix 1040:1045 a common formulation buffer matrix 1012:1045 a common formulation buffer matrix 1012:1045 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 22 theme reduced 890:896 arg1 interaction 903:913 further reduced FcγR interaction 882:913 further reduced FcγR interaction 882:913 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 6 23 theme Fc 1199:1200 arg1 position 1202:1209 the conserved N297 Fc position 1180:1209 the conserved N297 Fc position 1180:1209 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 24 from position 1202:1209 arg1 change 1315:1320 charge variant profile change 1292:1320 charge variant profile change 1292:1320 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 24 from position 1202:1209 arg1 fragmentation 1277:1289 fragmentation 1277:1289 fragmentation 1277:1289 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 24 from position 1202:1209 arg1 structure 1167:1175 N-linked glycan structure 1151:1175 N-linked glycan structure at the conserved N297 Fc position 1151:1209 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 24 from position 1202:1209 arg1 modification 1346:1357 post-translational modification 1327:1357 post-translational modification 1327:1357 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 24 from position 1202:1209 arg1 appearance 1221:1230 solution appearance 1212:1230 solution appearance at high concentration 1212:1252 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 24 from position 1202:1209 arg1 efficiency 1139:1148 host cell protein removal efficiency 1113:1148 host cell protein removal efficiency 1113:1148 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 24 from position 1202:1209 arg1 growth 1269:1274 aggregate growth 1259:1274 aggregate growth 1259:1274 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 24 from position 1202:1209 arg1 productivity 1099:1110 Chinese hamster ovary cell productivity 1072:1110 Chinese hamster ovary cell productivity 1072:1110 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 25 from temperature 1427:1437 arg1 conditions 1379:1388 thermal stress conditions 1364:1388 thermal stress conditions 1364:1388 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 25 from temperature 1427:1437 arg1 storage 1403:1409 long-term storage 1393:1409 long-term storage at refrigerated temperature 1393:1437 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 7 26 theme new 1589:1591 arg1 insight 1593:1599 new insight 1589:1599 new insight into the effects of IgG subclass on antibody manufacturability and stability 1589:1676 Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. 36945111 6 27 theme conserved 1184:1192 arg1 position 1202:1209 the conserved N297 Fc position 1180:1209 the conserved N297 Fc position 1180:1209 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 5 28 theme regions 757:763 arg1 regions 757:763 unrelated variable regions 738:763 unrelated variable regions 738:763 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 28 theme regions 757:763 arg1 sets 730:733 three sets 724:733 three sets of unrelated variable regions 724:763 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 2 29 theme Multiple 230:237 arg1 laboratories 239:250 Multiple laboratories 230:250 Multiple laboratories 230:250 Multiple laboratories have reported that the IgG subclasses possess different molecular characteristics that can affect their developability. 36945111 5 30 theme IgG4 864:867 arg1 variant 869:875 a stabilized IgG4 variant 851:875 a stabilized IgG4 variant with further reduced FcγR interaction 851:913 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 31 with variant 869:875 arg1 functions 830:838 diminished effector functions 810:838 diminished effector functions 810:838 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 31 with variant 869:875 arg1 interaction 903:913 further reduced FcγR interaction 882:913 further reduced FcγR interaction 882:913 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 6 32 theme stress 1372:1377 arg1 conditions 1379:1388 thermal stress conditions 1364:1388 thermal stress conditions 1364:1388 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 5 33 theme buffer 1033:1038 arg1 matrix 1040:1045 a common formulation buffer matrix 1012:1045 a common formulation buffer matrix 1012:1045 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 7 34 theme Fc 1567:1568 arg1 domains 1570:1576 certain Fc domains 1559:1576 certain Fc domains 1559:1576 Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. 36945111 0 35 from Impact 0:5 arg1 antibody 37:44 monoclonal antibody developability 26:59 monoclonal antibody developability 26:59 Impact of IgG subclass on monoclonal antibody developability. 36945111 7 36 from effects 1610:1616 arg1 stability 1668:1676 stability 1668:1676 stability 1668:1676 Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. 36945111 7 36 from effects 1610:1616 arg1 manufacturability 1646:1662 antibody manufacturability 1637:1662 antibody manufacturability 1637:1662 Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. 36945111 1 37 theme IgG-based 62:70 arg1 IgG1 123:126 IgG1 123:126 IgG1 123:126 IgG-based monoclonal antibody therapeutics, which are mainly IgG1, IgG2, and IgG4 subclasses or related variants, have dominated the biotherapeutics field for decades. 36945111 1 37 theme IgG-based 62:70 arg1 therapeutics 92:103 IgG-based monoclonal antibody therapeutics 62:103 IgG-based monoclonal antibody therapeutics 62:103 IgG-based monoclonal antibody therapeutics, which are mainly IgG1, IgG2, and IgG4 subclasses or related variants, have dominated the biotherapeutics field for decades. 36945111 5 38 theme unrelated 738:746 arg1 regions 757:763 unrelated variable regions 738:763 unrelated variable regions 738:763 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 8 39 theme development 1831:1841 arg1 process 1843:1849 their product development process 1817:1849 their product development process 1817:1849 These learnings can be used to enable a balanced decision on IgG subclass selection for therapeutic antibodies and aid in acceleration of their product development process. 36945111 1 40 theme antibody 83:90 arg1 IgG1 123:126 IgG1 123:126 IgG1 123:126 IgG-based monoclonal antibody therapeutics, which are mainly IgG1, IgG2, and IgG4 subclasses or related variants, have dominated the biotherapeutics field for decades. 36945111 1 40 theme antibody 83:90 arg1 therapeutics 92:103 IgG-based monoclonal antibody therapeutics 62:103 IgG-based monoclonal antibody therapeutics 62:103 IgG-based monoclonal antibody therapeutics, which are mainly IgG1, IgG2, and IgG4 subclasses or related variants, have dominated the biotherapeutics field for decades. 36945111 5 41 theme variable 748:755 arg1 regions 757:763 unrelated variable regions 738:763 unrelated variable regions 738:763 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 42 attach derived 711:717 arg2 each 766:769 each 766:769 each 766:769 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 42 attach derived 711:717 arg1 regions 757:763 unrelated variable regions 738:763 unrelated variable regions 738:763 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 42 attach derived 711:717 arg2 mAbs 706:709 12 mAbs 703:709 12 mAbs derived from three sets of unrelated variable regions 703:763 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 42 attach derived 711:717 arg1 sets 730:733 three sets 724:733 three sets of unrelated variable regions 724:763 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 43 theme IgG1 792:795 arg1 variant 797:803 an IgG1 variant 789:803 an IgG1 variant with diminished effector functions 789:838 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 0 44 theme IgG 10:12 arg1 subclass 14:21 IgG subclass 10:21 IgG subclass 10:21 Impact of IgG subclass on monoclonal antibody developability. 36945111 7 45 theme antibody 1637:1644 arg1 manufacturability 1646:1662 antibody manufacturability 1637:1662 antibody manufacturability 1637:1662 Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. 36945111 3 46 theme IgG 408:410 arg1 IgG1 385:388 IgG1 385:388 IgG1 385:388 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 3 46 theme IgG 408:410 arg1 subclass 412:419 the most popular IgG subclass 391:419 the most popular IgG subclass for therapeutics 391:436 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 6 47 theme refrigerated 1414:1425 arg1 temperature 1427:1437 refrigerated temperature 1414:1437 refrigerated temperature 1414:1437 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 2 48 contain possess 290:296 arg2 characteristics 318:332 different molecular characteristics 298:332 different molecular characteristics that can affect their developability 298:369 Multiple laboratories have reported that the IgG subclasses possess different molecular characteristics that can affect their developability. 36945111 2 48 contain possess 290:296 arg1 subclasses 279:288 the IgG subclasses 271:288 the IgG subclasses 271:288 Multiple laboratories have reported that the IgG subclasses possess different molecular characteristics that can affect their developability. 36945111 4 49 from subclasses 606:615 arg1 manufacturability 620:636 manufacturability 620:636 manufacturability 620:636 However, there remains a paucity of studies that systematically evaluate the IgG subclasses on manufacturability and long-term stability. 36945111 4 49 from subclasses 606:615 arg1 stability 652:660 long-term stability 642:660 long-term stability 642:660 However, there remains a paucity of studies that systematically evaluate the IgG subclasses on manufacturability and long-term stability. 36945111 6 50 theme host 1113:1116 arg1 efficiency 1139:1148 host cell protein removal efficiency 1113:1148 host cell protein removal efficiency 1113:1148 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 3 51 theme characteristic 458:471 arg1 pathway 485:491 a characteristic degradation pathway 456:491 a characteristic degradation pathway related to its hinge fragility 456:522 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 3 52 theme hinge 508:512 arg1 fragility 514:522 its hinge fragility 504:522 its hinge fragility 504:522 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 5 53 theme high 980:983 arg1 stability 999:1007 high concentration stability 980:1007 high concentration stability 980:1007 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 6 54 theme ovary 1088:1092 arg1 productivity 1099:1110 Chinese hamster ovary cell productivity 1072:1110 Chinese hamster ovary cell productivity 1072:1110 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 55 theme Chinese 1072:1078 arg1 productivity 1099:1110 Chinese hamster ovary cell productivity 1072:1110 Chinese hamster ovary cell productivity 1072:1110 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 4 56 theme studies 561:567 arg1 paucity 550:556 a paucity 548:556 a paucity of studies that systematically evaluate the IgG subclasses on manufacturability and long-term stability 548:660 However, there remains a paucity of studies that systematically evaluate the IgG subclasses on manufacturability and long-term stability. 36945111 6 57 theme aggregate 1259:1267 arg1 growth 1269:1274 aggregate growth 1259:1274 aggregate growth 1259:1274 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 8 58 used used 1702:1705 arg2 learnings 1685:1693 These learnings 1679:1693 These learnings 1679:1693 These learnings can be used to enable a balanced decision on IgG subclass selection for therapeutic antibodies and aid in acceleration of their product development process. 36945111 7 59 theme molecular 1463:1471 arg1 attributes 1473:1482 molecular attributes 1463:1482 molecular attributes that are common to all IgG subclasses 1463:1520 Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. 36945111 6 60 theme N-linked 1151:1158 arg1 structure 1167:1175 N-linked glycan structure 1151:1175 N-linked glycan structure at the conserved N297 Fc position 1151:1209 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 61 theme high 1235:1238 arg1 concentration 1240:1252 high concentration 1235:1252 high concentration 1235:1252 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 5 62 from manufacturability 958:974 arg1 matrix 1040:1045 a common formulation buffer matrix 1012:1045 a common formulation buffer matrix 1012:1045 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 7 63 theme subclass 1625:1632 arg1 effects 1610:1616 the effects 1606:1616 the effects of IgG subclass on antibody manufacturability and stability 1606:1676 Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. 36945111 2 64 theme different 298:306 arg1 characteristics 318:332 different molecular characteristics 298:332 different molecular characteristics that can affect their developability 298:369 Multiple laboratories have reported that the IgG subclasses possess different molecular characteristics that can affect their developability. 36945111 5 65 theme diminished 810:819 arg1 functions 830:838 diminished effector functions 810:838 diminished effector functions 810:838 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 6 66 theme protein 1123:1129 arg1 efficiency 1139:1148 host cell protein removal efficiency 1113:1148 host cell protein removal efficiency 1113:1148 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 5 67 from stability 999:1007 arg1 matrix 1040:1045 a common formulation buffer matrix 1012:1045 a common formulation buffer matrix 1012:1045 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 6 68 theme solution 1212:1219 arg1 appearance 1221:1230 solution appearance 1212:1230 solution appearance at high concentration 1212:1252 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 4 69 theme long-term 642:650 arg1 stability 652:660 long-term stability 642:660 long-term stability 642:660 However, there remains a paucity of studies that systematically evaluate the IgG subclasses on manufacturability and long-term stability. 36945111 6 70 theme variant 1299:1305 arg1 change 1315:1320 charge variant profile change 1292:1320 charge variant profile change 1292:1320 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 8 71 theme IgG 1740:1742 arg1 selection 1753:1761 IgG subclass selection 1740:1761 IgG subclass selection 1740:1761 These learnings can be used to enable a balanced decision on IgG subclass selection for therapeutic antibodies and aid in acceleration of their product development process. 36945111 5 72 theme formulation 1021:1031 arg1 matrix 1040:1045 a common formulation buffer matrix 1012:1045 a common formulation buffer matrix 1012:1045 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 5 73 theme FcγR 898:901 arg1 interaction 903:913 further reduced FcγR interaction 882:913 further reduced FcγR interaction 882:913 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 6 74 theme N297 1194:1197 arg1 position 1202:1209 the conserved N297 Fc position 1180:1209 the conserved N297 Fc position 1180:1209 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 75 link N-linked 1151:1158 arg1 structure 1167:1175 N-linked glycan structure 1151:1175 N-linked glycan structure at the conserved N297 Fc position 1151:1209 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 76 theme long-term 1393:1401 arg1 storage 1403:1409 long-term storage 1393:1409 long-term storage at refrigerated temperature 1393:1437 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 8 77 theme therapeutic 1767:1777 arg1 antibodies 1779:1788 therapeutic antibodies 1767:1788 therapeutic antibodies 1767:1788 These learnings can be used to enable a balanced decision on IgG subclass selection for therapeutic antibodies and aid in acceleration of their product development process. 36945111 5 78 theme stabilized 853:862 arg1 variant 869:875 a stabilized IgG4 variant 851:875 a stabilized IgG4 variant with further reduced FcγR interaction 851:913 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 7 79 theme certain 1559:1565 arg1 domains 1570:1576 certain Fc domains 1559:1576 certain Fc domains 1559:1576 Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. 36945111 6 80 theme thermal 1364:1370 arg1 conditions 1379:1388 thermal stress conditions 1364:1388 thermal stress conditions 1364:1388 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 1 81 theme monoclonal 72:81 arg1 IgG1 123:126 IgG1 123:126 IgG1 123:126 IgG-based monoclonal antibody therapeutics, which are mainly IgG1, IgG2, and IgG4 subclasses or related variants, have dominated the biotherapeutics field for decades. 36945111 1 81 theme monoclonal 72:81 arg1 therapeutics 92:103 IgG-based monoclonal antibody therapeutics 62:103 IgG-based monoclonal antibody therapeutics 62:103 IgG-based monoclonal antibody therapeutics, which are mainly IgG1, IgG2, and IgG4 subclasses or related variants, have dominated the biotherapeutics field for decades. 36945111 1 82 dep IgG1 123:126 arg1 subclasses 144:153 subclasses 144:153 subclasses 144:153 IgG-based monoclonal antibody therapeutics, which are mainly IgG1, IgG2, and IgG4 subclasses or related variants, have dominated the biotherapeutics field for decades. 36945111 8 83 theme product 1823:1829 arg1 process 1843:1849 their product development process 1817:1849 their product development process 1817:1849 These learnings can be used to enable a balanced decision on IgG subclass selection for therapeutic antibodies and aid in acceleration of their product development process. 36945111 0 84 theme subclass 14:21 arg1 Impact 0:5 Impact 0:5 Impact of IgG subclass on monoclonal antibody developability. 0:60 Impact of IgG subclass on monoclonal antibody developability. 36945111 8 85 theme process 1843:1849 arg1 acceleration 1801:1812 acceleration 1801:1812 acceleration of their product development process 1801:1849 These learnings can be used to enable a balanced decision on IgG subclass selection for therapeutic antibodies and aid in acceleration of their product development process. 36945111 5 86 theme IgG 942:944 arg1 subclass 946:953 IgG subclass 942:953 IgG subclass 942:953 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 0 87 theme monoclonal 26:35 arg1 antibody 37:44 monoclonal antibody developability 26:59 monoclonal antibody developability 26:59 Impact of IgG subclass on monoclonal antibody developability. 36945111 5 88 theme concentration 985:997 arg1 stability 999:1007 high concentration stability 980:1007 high concentration stability 980:1007 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 6 89 theme post-translational 1327:1344 arg1 modification 1346:1357 post-translational modification 1327:1357 post-translational modification 1327:1357 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 6 90 theme cell 1118:1121 arg1 efficiency 1139:1148 host cell protein removal efficiency 1113:1148 host cell protein removal efficiency 1113:1148 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36945111 3 91 theme popular 400:406 arg1 IgG1 385:388 IgG1 385:388 IgG1 385:388 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 3 91 theme popular 400:406 arg1 subclass 412:419 the most popular IgG subclass 391:419 the most popular IgG subclass for therapeutics 391:436 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 3 92 theme related 493:499 arg1 pathway 485:491 a characteristic degradation pathway 456:491 a characteristic degradation pathway related to its hinge fragility 456:522 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 4 93 theme IgG 602:604 arg1 subclasses 606:615 the IgG subclasses 598:615 the IgG subclasses on manufacturability and long-term stability 598:660 However, there remains a paucity of studies that systematically evaluate the IgG subclasses on manufacturability and long-term stability. 36945111 5 94 theme subclass 946:953 arg1 impact 932:937 the impact 928:937 the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix 928:1045 We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. 36945111 8 95 from decision 1728:1735 arg1 selection 1753:1761 IgG subclass selection 1740:1761 IgG subclass selection 1740:1761 These learnings can be used to enable a balanced decision on IgG subclass selection for therapeutic antibodies and aid in acceleration of their product development process. 36945111 3 96 theme degradation 473:483 arg1 pathway 485:491 a characteristic degradation pathway 456:491 a characteristic degradation pathway related to its hinge fragility 456:522 For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. 36945111 6 97 theme cell 1094:1097 arg1 productivity 1099:1110 Chinese hamster ovary cell productivity 1072:1110 Chinese hamster ovary cell productivity 1072:1110 Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. 36718587 4 0 theme death 829:833 arg1 lacunae 780:786 the osteocytic lacunae 765:786 the osteocytic lacunae 765:786 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 4 0 theme death 829:833 arg1 levels 803:808 increased levels 793:808 increased levels 793:808 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 3 1 theme PTH 479:481 arg1 levels 512:517 serum PTH and inorganic phosphate (Pi) levels 473:517 serum PTH and inorganic phosphate (Pi) levels 473:517 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 3 2 theme serum 473:477 arg1 PTH 479:481 serum PTH 473:481 serum PTH 473:481 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 8 3 theme osteocytic 1673:1682 arg1 lacunae 1684:1690 osteocytic lacunae 1673:1690 osteocytic lacunae 1673:1690 It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats. 36718587 7 4 theme serum 1439:1443 arg1 PTH 1445:1447 the highly-concentrated serum PTH 1415:1447 the highly-concentrated serum PTH 1415:1447 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 4 5 theme levels 803:808 arg1 periphery 752:760 the periphery 748:760 the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity 748:903 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 8 6 from porosity 1747:1754 arg1 rats 1768:1771 CKD-SHPT rats 1759:1771 CKD-SHPT rats 1759:1771 It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats. 36718587 4 7 theme osteocytic 813:822 arg1 death 829:833 osteocytic cell death 813:833 osteocytic cell death 813:833 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 7 8 theme osteocytic 1365:1374 arg1 death 1376:1380 osteocytic death 1365:1380 osteocytic death 1365:1380 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 4 9 theme cortical 606:613 arg1 bone 615:618 The cortical bone 602:618 The cortical bone of the CKD-SHPT rats 602:639 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 3 10 theme bone 525:528 arg1 turnover 530:537 high bone turnover 520:537 high bone turnover 520:537 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 8 11 theme cell 1707:1710 arg1 death 1712:1716 osteocytic cell death 1696:1716 osteocytic cell death 1696:1716 It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats. 36718587 1 12 theme secondary 183:191 arg1 SHPT 214:217 SHPT 214:217 SHPT 214:217 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 1 12 theme secondary 183:191 arg1 hyperparathyroidism 193:211 secondary hyperparathyroidism 183:211 secondary hyperparathyroidism (SHPT) 183:218 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 7 13 theme Pit1 1336:1339 arg1 expression 1341:1350 Pit1 expression 1336:1350 Pit1 expression 1336:1350 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 3 14 theme severe 544:549 arg1 porosity 560:567 severe cortical porosity 544:567 severe cortical porosity 544:567 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 5 15 theme enlarged 977:984 arg1 lacunae 997:1003 the enlarged osteocytic lacunae 973:1003 the enlarged osteocytic lacunae 973:1003 In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae and the cortical porosity of the CKD-SHPT rats. 36718587 7 16 theme PTH 1300:1302 arg1 administration 1304:1317 PTH administration 1300:1317 PTH administration 1300:1317 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 8 17 theme CKD-SHPT 1759:1766 arg1 rats 1768:1771 CKD-SHPT rats 1759:1771 CKD-SHPT rats 1759:1771 It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats. 36718587 6 18 theme extracellular 1140:1152 arg1 Pi 1154:1155 extracellular Pi 1140:1155 extracellular Pi 1140:1155 Osteocytes of CKD-SHPT rats strongly expressed PTH receptor and Pit1/Pit2, which sense extracellular Pi, indicating that PTH and Pi affected these osteocytes. 36718587 2 19 theme administered 391:402 arg1 groups 404:409 evocalcet administered groups 381:409 evocalcet administered groups 381:409 The treated rats were then divided into vehicle groups and evocalcet administered groups. 36718587 0 20 theme kidney 84:89 arg1 disease 91:97 chronic kidney disease 76:97 chronic kidney disease male rats 76:107 Evocalcet rescues secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats. 36718587 3 21 theme porosity 560:567 arg1 levels 463:468 increased levels 453:468 increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity 453:567 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 1 22 theme new 150:152 arg1 evocalcet 137:145 evocalcet 137:145 evocalcet 137:145 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 1 22 theme new 150:152 arg1 calcimimetic 159:170 a new oral calcimimetic 148:170 a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD) 148:252 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 4 23 theme CKD-SHPT 627:634 arg1 rats 636:639 the CKD-SHPT rats 623:639 the CKD-SHPT rats 623:639 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 0 24 theme male 99:102 arg1 rats 104:107 chronic kidney disease male rats 76:107 chronic kidney disease male rats 76:107 Evocalcet rescues secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats. 36718587 1 25 with calcimimetic 159:170 arg1 CKD 249:251 CKD 249:251 CKD 249:251 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 1 25 with calcimimetic 159:170 arg1 disease 240:246 chronic kidney disease 225:246 chronic kidney disease (CKD) 225:252 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 4 26 theme cortical 887:894 arg1 porosity 896:903 cortical porosity 887:903 cortical porosity 887:903 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 4 27 theme Phex/SIBLING-mediated 708:728 arg1 mineralization 730:743 Phex/SIBLING-mediated mineralization 708:743 Phex/SIBLING-mediated mineralization 708:743 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 2 28 theme vehicle 362:368 arg1 groups 370:375 vehicle groups 362:375 vehicle groups 362:375 The treated rats were then divided into vehicle groups and evocalcet administered groups. 36718587 5 29 theme rats 1047:1050 arg1 lacunae 997:1003 the enlarged osteocytic lacunae 973:1003 the enlarged osteocytic lacunae 973:1003 In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae and the cortical porosity of the CKD-SHPT rats. 36718587 5 29 theme rats 1047:1050 arg1 levels 965:970 the increased serum PTH levels 941:970 the increased serum PTH levels 941:970 In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae and the cortical porosity of the CKD-SHPT rats. 36718587 5 29 theme rats 1047:1050 arg1 porosity 1022:1029 the cortical porosity 1009:1029 the cortical porosity of the CKD-SHPT rats 1009:1050 In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae and the cortical porosity of the CKD-SHPT rats. 36718587 7 30 theme Pi 1261:1262 arg1 manner 1288:1293 a Pi concentration-dependent manner 1259:1293 a Pi concentration-dependent manner 1259:1293 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 3 31 theme vehicle 428:434 arg1 groups 436:441 the vehicle groups 424:441 the vehicle groups 424:441 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 0 32 theme secondary 18:26 arg1 porosity 64:71 secondary hyperparathyroidism-driven cortical porosity 18:71 secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats 18:107 Evocalcet rescues secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats. 36718587 4 33 theme lacunae 780:786 arg1 periphery 752:760 the periphery 748:760 the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity 748:903 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 0 34 theme cortical 55:62 arg1 porosity 64:71 secondary hyperparathyroidism-driven cortical porosity 18:71 secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats 18:107 Evocalcet rescues secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats. 36718587 7 35 theme osteocytic 1497:1506 arg1 death 1513:1517 osteocytic cell death 1497:1517 osteocytic cell death 1497:1517 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 7 36 theme osteocytes 1235:1244 arg1 death 1217:1221 Cell death 1212:1221 Cell death of cultured osteocytes 1212:1244 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 2 37 dep administered 391:402 arg1 evocalcet 381:389 evocalcet 381:389 evocalcet 381:389 The treated rats were then divided into vehicle groups and evocalcet administered groups. 36718587 6 38 theme CKD-SHPT 1067:1074 arg1 rats 1076:1079 CKD-SHPT rats 1067:1079 CKD-SHPT rats 1067:1079 Osteocytes of CKD-SHPT rats strongly expressed PTH receptor and Pit1/Pit2, which sense extracellular Pi, indicating that PTH and Pi affected these osteocytes. 36718587 7 39 theme severe 1462:1467 arg1 osteolysis 1482:1491 severe peri-lacunar osteolysis 1462:1491 severe peri-lacunar osteolysis 1462:1491 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 7 40 theme Cell 1212:1215 arg1 death 1217:1221 Cell death 1212:1221 Cell death of cultured osteocytes 1212:1244 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 1 41 theme kidney 233:238 arg1 CKD 249:251 CKD 249:251 CKD 249:251 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 1 41 theme kidney 233:238 arg1 disease 240:246 chronic kidney disease 225:246 chronic kidney disease (CKD) 225:252 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 5 42 theme serum 955:959 arg1 levels 965:970 the increased serum PTH levels 941:970 the increased serum PTH levels 941:970 In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae and the cortical porosity of the CKD-SHPT rats. 36718587 3 43 from rats 416:419 arg1 groups 436:441 the vehicle groups 424:441 the vehicle groups 424:441 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 2 44 theme treated 326:332 arg1 rats 334:337 The treated rats 322:337 The treated rats 322:337 The treated rats were then divided into vehicle groups and evocalcet administered groups. 36718587 4 45 theme cell 824:827 arg1 death 829:833 osteocytic cell death 813:833 osteocytic cell death 813:833 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 7 46 theme highly-concentrated 1419:1437 arg1 PTH 1445:1447 the highly-concentrated serum PTH 1415:1447 the highly-concentrated serum PTH 1415:1447 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 3 47 theme phosphate 497:505 arg1 levels 512:517 serum PTH and inorganic phosphate (Pi) levels 473:517 serum PTH and inorganic phosphate (Pi) levels 473:517 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 4 48 theme increased 793:801 arg1 levels 803:808 increased levels 793:808 increased levels 793:808 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 3 49 theme high 520:523 arg1 turnover 530:537 high bone turnover 520:537 high bone turnover 520:537 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 8 50 theme lacunae 1684:1690 arg1 demineralization 1653:1668 the demineralization 1649:1668 the demineralization of osteocytic lacunae and osteocytic cell death 1649:1716 It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats. 36718587 6 51 theme PTH 1100:1102 arg1 receptor 1104:1111 PTH receptor 1100:1111 PTH receptor 1100:1111 Osteocytes of CKD-SHPT rats strongly expressed PTH receptor and Pit1/Pit2, which sense extracellular Pi, indicating that PTH and Pi affected these osteocytes. 36718587 3 52 theme levels 512:517 arg1 levels 463:468 increased levels 453:468 increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity 453:567 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 8 53 theme osteocytic 1696:1705 arg1 death 1712:1716 osteocytic cell death 1696:1716 osteocytic cell death 1696:1716 It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats. 36718587 1 54 theme hyperparathyroidism 193:211 arg1 bone 175:178 bone 175:178 bone of secondary hyperparathyroidism (SHPT) 175:218 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 5 55 theme cortical 1013:1020 arg1 porosity 1022:1029 the cortical porosity 1009:1029 the cortical porosity of the CKD-SHPT rats 1009:1050 In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae and the cortical porosity of the CKD-SHPT rats. 36718587 8 56 theme death 1712:1716 arg1 demineralization 1653:1668 the demineralization 1649:1668 the demineralization of osteocytic lacunae and osteocytic cell death 1649:1716 It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats. 36718587 4 57 theme first 872:876 arg1 all 836:838 all 836:838 all 836:838 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 4 57 theme first 872:876 arg1 levels 803:808 increased levels 793:808 increased levels 793:808 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 4 57 theme first 872:876 arg1 steps 878:882 the first steps 868:882 the first steps of cortical porosity 868:903 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 3 58 theme turnover 530:537 arg1 levels 463:468 increased levels 453:468 increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity 453:567 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 4 59 theme rats 636:639 arg1 bone 615:618 The cortical bone 602:618 The cortical bone of the CKD-SHPT rats 602:639 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 5 60 theme osteocytic 986:995 arg1 lacunae 997:1003 the enlarged osteocytic lacunae 973:1003 the enlarged osteocytic lacunae 973:1003 In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae and the cortical porosity of the CKD-SHPT rats. 36718587 8 61 theme cortical 1738:1745 arg1 porosity 1747:1754 cortical porosity 1738:1754 cortical porosity in CKD-SHPT rats 1738:1771 It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats. 36718587 1 62 theme evocalcet 137:145 arg1 effect 127:132 the effect 123:132 the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD) 123:252 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 4 63 theme broad 648:652 arg1 demineralization 654:669 broad demineralization 648:669 broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization 648:743 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 0 64 theme disease 91:97 arg1 rats 104:107 chronic kidney disease male rats 76:107 chronic kidney disease male rats 76:107 Evocalcet rescues secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats. 36718587 3 65 theme cortical 551:558 arg1 porosity 560:567 severe cortical porosity 544:567 severe cortical porosity 544:567 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 1 66 theme high-phosphate 301:314 arg1 diet 316:319 a high-phosphate diet 299:319 a high-phosphate diet 299:319 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 1 67 theme oral 154:157 arg1 evocalcet 137:145 evocalcet 137:145 evocalcet 137:145 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 1 67 theme oral 154:157 arg1 calcimimetic 159:170 a new oral calcimimetic 148:170 a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD) 148:252 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 5 68 theme CKD-SHPT 1038:1045 arg1 rats 1047:1050 the CKD-SHPT rats 1034:1050 the CKD-SHPT rats 1034:1050 In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae and the cortical porosity of the CKD-SHPT rats. 36718587 7 69 theme concentration-dependent 1264:1286 arg1 manner 1288:1293 a Pi concentration-dependent manner 1259:1293 a Pi concentration-dependent manner 1259:1293 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 4 70 theme porosity 896:903 arg1 all 836:838 all 836:838 all 836:838 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 4 70 theme porosity 896:903 arg1 levels 803:808 increased levels 793:808 increased levels 793:808 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 4 70 theme porosity 896:903 arg1 steps 878:882 the first steps 868:882 the first steps of cortical porosity 868:903 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 0 71 from porosity 64:71 arg1 rats 104:107 chronic kidney disease male rats 76:107 chronic kidney disease male rats 76:107 Evocalcet rescues secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats. 36718587 4 72 theme mineralization 730:743 arg1 suppression 693:703 the osteocytes suppression 678:703 the osteocytes suppression of Phex/SIBLING-mediated mineralization 678:743 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 0 73 theme hyperparathyroidism-driven 28:53 arg1 porosity 64:71 secondary hyperparathyroidism-driven cortical porosity 18:71 secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats 18:107 Evocalcet rescues secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats. 36718587 3 74 theme CKD-SHPT 586:593 arg1 SHPT 580:583 SHPT 580:583 SHPT (CKD-SHPT rats) 580:599 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 3 74 theme CKD-SHPT 586:593 arg1 rats 595:598 CKD-SHPT rats 586:598 CKD-SHPT rats 586:598 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 4 75 theme osteocytes 682:691 arg1 suppression 693:703 the osteocytes suppression 678:703 the osteocytes suppression of Phex/SIBLING-mediated mineralization 678:743 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 5 76 theme PTH 961:963 arg1 levels 965:970 the increased serum PTH levels 941:970 the increased serum PTH levels 941:970 In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae and the cortical porosity of the CKD-SHPT rats. 36718587 7 77 theme cultured 1226:1233 arg1 osteocytes 1235:1244 cultured osteocytes 1226:1244 cultured osteocytes 1226:1244 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 4 78 theme osteocytic 769:778 arg1 lacunae 780:786 the osteocytic lacunae 765:786 the osteocytic lacunae 765:786 The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes suppression of Phex/SIBLING-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. 36718587 0 79 theme chronic 76:82 arg1 disease 91:97 chronic kidney disease 76:97 chronic kidney disease male rats 76:107 Evocalcet rescues secondary hyperparathyroidism-driven cortical porosity in chronic kidney disease male rats. 36718587 7 80 theme cell 1508:1511 arg1 death 1513:1517 osteocytic cell death 1497:1517 osteocytic cell death 1497:1517 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 6 81 theme rats 1076:1079 arg1 Osteocytes 1053:1062 Osteocytes 1053:1062 Osteocytes of CKD-SHPT rats 1053:1079 Osteocytes of CKD-SHPT rats strongly expressed PTH receptor and Pit1/Pit2, which sense extracellular Pi, indicating that PTH and Pi affected these osteocytes. 36718587 8 82 theme serum 1577:1581 arg1 PTH 1583:1585 serum PTH 1577:1585 serum PTH 1577:1585 It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats. 36718587 3 83 theme increased 453:461 arg1 levels 463:468 increased levels 453:468 increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity 453:567 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 1 84 theme chronic 225:231 arg1 CKD 249:251 CKD 249:251 CKD 249:251 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 1 84 theme chronic 225:231 arg1 disease 240:246 chronic kidney disease 225:246 chronic kidney disease (CKD) 225:252 To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. 36718587 7 85 theme peri-lacunar 1469:1480 arg1 osteolysis 1482:1491 severe peri-lacunar osteolysis 1462:1491 severe peri-lacunar osteolysis 1462:1491 Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly-concentrated serum PTH and Pi cause severe peri-lacunar osteolysis and osteocytic cell death. 36718587 5 86 theme increased 945:953 arg1 levels 965:970 the increased serum PTH levels 941:970 the increased serum PTH levels 941:970 In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae and the cortical porosity of the CKD-SHPT rats. 36718587 3 87 theme inorganic 487:495 arg1 Pi 508:509 Pi 508:509 Pi 508:509 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36718587 3 87 theme inorganic 487:495 arg1 phosphate 497:505 inorganic phosphate 487:505 inorganic phosphate (Pi) 487:510 The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). 36577688 5 0 theme click 833:837 arg1 chemistry 839:847 a cleavable linker via click chemistry 810:847 a cleavable linker via click chemistry 810:847 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 8 1 theme biological 1290:1299 arg1 signaling 1364:1372 plant hormone signaling 1350:1372 plant hormone signaling 1350:1372 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 8 1 theme biological 1290:1299 arg1 translation 1334:1344 translation 1334:1344 translation 1334:1344 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 8 1 theme biological 1290:1299 arg1 processes 1301:1309 multiple biological processes 1281:1309 multiple biological processes such as transcription, translation and plant hormone signaling 1281:1372 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 8 1 theme biological 1290:1299 arg1 transcription 1319:1331 transcription 1319:1331 transcription 1319:1331 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 10 2 theme identified 1595:1604 arg1 proteins 1626:1633 the identified rice O-GlcNAcylated proteins 1591:1633 the identified rice O-GlcNAcylated proteins 1591:1633 By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. 36577688 5 3 theme spectrometry 909:920 arg1 analysis 927:934 mass spectrometry (MS) analysis 904:934 mass spectrometry (MS) analysis 904:934 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 10 4 dep expressing 1449:1458 arg1 leaves 1513:1518 leaves 1513:1518 expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves 1449:1518 By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. 36577688 8 5 theme O-GlcNAcylated 1241:1254 arg1 proteins 1256:1263 The identified O-GlcNAcylated proteins 1226:1263 The identified O-GlcNAcylated proteins 1226:1263 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 1 6 link O-linked 105:112 arg1 modification 194:205 a ubiquitous posttranslational modification 163:205 a ubiquitous posttranslational modification occurring in both animals and plants 163:242 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. 36577688 1 6 link O-linked 105:112 arg1 O-GlcNAcylation 143:157 O-GlcNAcylation 143:157 O-GlcNAcylation 143:157 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. 36577688 1 6 link O-linked 105:112 arg1 β-N-acetylglucosaminylation 114:140 O-linked β-N-acetylglucosaminylation 105:140 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 105:158 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. 36577688 0 7 from profiling 15:23 arg1 rice 99:102 rice 99:102 rice 99:102 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 10 8 theme O-GlcNAcylated 1611:1624 arg1 proteins 1626:1633 the identified rice O-GlcNAcylated proteins 1591:1633 the identified rice O-GlcNAcylated proteins 1591:1633 By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. 36577688 2 9 from proteomes 377:385 arg1 plants 390:395 plants 390:395 plants 390:395 Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. 36577688 11 10 theme valuable 1659:1666 arg1 resource 1668:1675 a valuable resource 1657:1675 a valuable resource for studying O-GlcNAc biology in rice 1657:1713 Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants. 36577688 4 11 theme glycan 560:565 arg1 labeling 567:574 metabolic glycan labeling 550:574 the metabolic glycan labeling strategy (MGL) 546:589 We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. 36577688 10 12 theme OGT 1540:1542 arg1 activities 1554:1563 their OGT enzymatic activities 1534:1563 their OGT enzymatic activities 1534:1563 By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. 36577688 2 13 theme animal 338:343 arg1 systems 345:351 various animal systems 330:351 various animal systems 330:351 Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. 36577688 6 14 theme O-GlcNAcylation 966:980 arg1 sites 982:986 1,591 unambiguous O-GlcNAcylation sites 948:986 1,591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins 948:1029 A total of 1,591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins were identified. 36577688 11 15 theme O-GlcNAc 1690:1697 arg1 biology 1699:1705 O-GlcNAc biology 1690:1705 O-GlcNAc biology in rice 1690:1713 Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants. 36577688 2 16 theme various 330:336 arg1 systems 345:351 various animal systems 330:351 various animal systems 330:351 Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. 36577688 4 17 theme rice 635:638 arg1 seedlings 640:648 rice seedlings 635:648 rice seedlings 635:648 We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. 36577688 0 18 from identification 56:69 arg1 rice 99:102 rice 99:102 rice 99:102 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 10 19 from OsOGTs 1460:1465 arg1 coli 1482:1485 Escherichia coli 1470:1485 Escherichia coli 1470:1485 By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. 36577688 5 20 with conjugation 733:743 arg1 alkyne-biotin 785:797 alkyne-biotin 785:797 alkyne-biotin containing a cleavable linker via click chemistry 785:847 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 5 21 theme cleavable 812:820 arg1 chemistry 839:847 a cleavable linker via click chemistry 810:847 a cleavable linker via click chemistry 810:847 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 5 22 contain containing 799:808 arg2 chemistry 839:847 a cleavable linker via click chemistry 810:847 a cleavable linker via click chemistry 810:847 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 5 22 contain containing 799:808 arg1 alkyne-biotin 785:797 alkyne-biotin 785:797 alkyne-biotin containing a cleavable linker via click chemistry 785:847 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 11 23 theme MGL 1724:1726 arg1 method 1728:1733 the MGL method 1720:1733 the MGL method 1720:1733 Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants. 36577688 7 24 theme ambiguous 1199:1207 arg1 assignment 1214:1223 ambiguous site assignment 1199:1223 ambiguous site assignment 1199:1223 Additionally, 102 O-GlcNAcylated proteins were identified with their O-GlcNAcylation sites located within a serine/threonine-enriched peptide, causing ambiguous site assignment. 36577688 11 25 theme proteins 1790:1797 arg1 identification 1757:1770 the identification 1753:1770 the identification of O-GlcNAcylated proteins in various plants 1753:1815 Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants. 36577688 10 26 used used 1569:1572 arg2 we 1521:1522 we 1521:1522 we 1521:1522 By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. 36577688 4 27 theme bioorthogonal 694:706 arg1 handle 708:713 a bioorthogonal handle 692:713 a bioorthogonal handle into O-GlcNAc 692:727 We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. 36577688 4 27 theme bioorthogonal 694:706 arg1 incorporation 665:677 incorporation 665:677 incorporation of azides 665:687 We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. 36577688 8 28 theme multiple 1281:1288 arg1 signaling 1364:1372 plant hormone signaling 1350:1372 plant hormone signaling 1350:1372 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 8 28 theme multiple 1281:1288 arg1 translation 1334:1344 translation 1334:1344 translation 1334:1344 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 8 28 theme multiple 1281:1288 arg1 processes 1301:1309 multiple biological processes 1281:1309 multiple biological processes such as transcription, translation and plant hormone signaling 1281:1372 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 8 28 theme multiple 1281:1288 arg1 transcription 1319:1331 transcription 1319:1331 transcription 1319:1331 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 7 29 theme site 1209:1212 arg1 assignment 1214:1223 ambiguous site assignment 1199:1223 ambiguous site assignment 1199:1223 Additionally, 102 O-GlcNAcylated proteins were identified with their O-GlcNAcylation sites located within a serine/threonine-enriched peptide, causing ambiguous site assignment. 36577688 5 30 theme linker 822:827 arg1 chemistry 839:847 a cleavable linker via click chemistry 810:847 a cleavable linker via click chemistry 810:847 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 11 31 from identification 1757:1770 arg1 plants 1810:1815 various plants 1802:1815 various plants 1802:1815 Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants. 36577688 6 32 theme unambiguous 954:964 arg1 sites 982:986 1,591 unambiguous O-GlcNAcylation sites 948:986 1,591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins 948:1029 A total of 1,591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins were identified. 36577688 3 33 theme protein 466:472 arg1 O-GlcNAcylation 474:488 protein O-GlcNAcylation 466:488 protein O-GlcNAcylation 466:488 Here, we report a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice. 36577688 0 34 theme Chemoproteomic 0:13 arg1 profiling 15:23 Chemoproteomic profiling 0:23 Chemoproteomic profiling of O-GlcNAcylated proteins 0:50 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 8 35 theme identified 1230:1239 arg1 proteins 1256:1263 The identified O-GlcNAcylated proteins 1226:1263 The identified O-GlcNAcylated proteins 1226:1263 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 10 36 theme rice 1606:1609 arg1 proteins 1626:1633 the identified rice O-GlcNAcylated proteins 1591:1633 the identified rice O-GlcNAcylated proteins 1591:1633 By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. 36577688 1 37 theme O-linked 105:112 arg1 modification 194:205 a ubiquitous posttranslational modification 163:205 a ubiquitous posttranslational modification occurring in both animals and plants 163:242 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. 36577688 1 37 theme O-linked 105:112 arg1 O-GlcNAcylation 143:157 O-GlcNAcylation 143:157 O-GlcNAcylation 143:157 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. 36577688 1 37 theme O-linked 105:112 arg1 β-N-acetylglucosaminylation 114:140 O-linked β-N-acetylglucosaminylation 105:140 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 105:158 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. 36577688 3 38 theme O-GlcNAcylation 474:488 arg1 profiling 453:461 a large-scale profiling 439:461 a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice 439:522 Here, we report a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice. 36577688 0 39 theme O-GlcNAcylated 28:41 arg1 proteins 43:50 O-GlcNAcylated proteins 28:50 O-GlcNAcylated proteins 28:50 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 8 40 theme plant 1350:1354 arg1 signaling 1364:1372 plant hormone signaling 1350:1372 plant hormone signaling 1350:1372 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 10 41 theme enzymatic 1544:1552 arg1 activities 1554:1563 their OGT enzymatic activities 1534:1563 their OGT enzymatic activities 1534:1563 By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. 36577688 2 42 dep along 267:271 arg1 with 273:276 with 273:276 with 273:276 Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. 36577688 5 43 theme mass 904:907 arg1 MS 923:924 MS 923:924 MS 923:924 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 5 43 theme mass 904:907 arg1 spectrometry 909:920 mass spectrometry 904:920 mass spectrometry (MS) analysis 904:934 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 5 44 theme azide-incorporated 752:769 arg1 O-GlcNAc 771:778 the azide-incorporated O-GlcNAc 748:778 the azide-incorporated O-GlcNAc 748:778 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 0 45 from rice 99:102 arg1 identification 56:69 identification 56:69 identification of O-GlcNAc transferases in rice 56:102 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 0 45 from rice 99:102 arg1 profiling 15:23 Chemoproteomic profiling 0:23 Chemoproteomic profiling of O-GlcNAcylated proteins 0:50 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 10 46 from benthamiana 1501:1511 arg1 coli 1482:1485 Escherichia coli 1470:1485 Escherichia coli 1470:1485 By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. 36577688 11 47 theme various 1802:1808 arg1 plants 1810:1815 various plants 1802:1815 various plants 1802:1815 Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants. 36577688 5 48 theme O-GlcNAc 771:778 arg1 conjugation 733:743 conjugation 733:743 conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry 733:847 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 11 49 from proteins 1790:1797 arg1 plants 1810:1815 various plants 1802:1815 various plants 1802:1815 Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants. 36577688 3 50 theme site-specific 495:507 arg1 manner 509:514 a site-specific manner 493:514 a site-specific manner in rice 493:522 Here, we report a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice. 36577688 0 51 theme proteins 43:50 arg1 identification 56:69 identification 56:69 identification of O-GlcNAc transferases in rice 56:102 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 0 51 theme proteins 43:50 arg1 profiling 15:23 Chemoproteomic profiling 0:23 Chemoproteomic profiling of O-GlcNAcylated proteins 0:50 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 5 52 theme O-GlcNAcylated 850:863 arg1 proteins 865:872 O-GlcNAcylated proteins 850:872 O-GlcNAcylated proteins 850:872 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 0 53 from transferases 83:94 arg1 rice 99:102 rice 99:102 rice 99:102 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 4 54 from N-azidoacetylgalactosamine 596:621 arg1 seedlings 640:648 rice seedlings 635:648 rice seedlings 635:648 We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. 36577688 4 55 theme labeling 567:574 arg1 MGL 586:588 MGL 586:588 MGL 586:588 We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. 36577688 4 55 theme labeling 567:574 arg1 strategy 576:583 the metabolic glycan labeling strategy 546:583 the metabolic glycan labeling strategy (MGL) 546:589 We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. 36577688 11 56 from plants 1810:1815 arg1 identification 1757:1770 the identification 1753:1770 the identification of O-GlcNAcylated proteins in various plants 1753:1815 Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants. 36577688 8 57 theme hormone 1356:1362 arg1 signaling 1364:1372 plant hormone signaling 1350:1372 plant hormone signaling 1350:1372 The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. 36577688 5 58 theme via 829:831 arg1 chemistry 839:847 a cleavable linker via click chemistry 810:847 a cleavable linker via click chemistry 810:847 By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. 36577688 3 59 from manner 509:514 arg1 rice 519:522 rice 519:522 rice 519:522 Here, we report a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice. 36577688 3 60 theme large-scale 441:451 arg1 profiling 453:461 a large-scale profiling 439:461 a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice 439:522 Here, we report a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice. 36577688 7 61 theme serine/threonine-enriched 1156:1180 arg1 peptide 1182:1188 a serine/threonine-enriched peptide 1154:1188 a serine/threonine-enriched peptide 1154:1188 Additionally, 102 O-GlcNAcylated proteins were identified with their O-GlcNAcylation sites located within a serine/threonine-enriched peptide, causing ambiguous site assignment. 36577688 9 62 theme O-GlcNAc 1406:1413 arg1 transferases 1415:1426 two O-GlcNAc transferases 1402:1426 two O-GlcNAc transferases (OsOGTs) 1402:1435 Furthermore, we discovered two O-GlcNAc transferases (OsOGTs) in rice. 36577688 9 62 theme O-GlcNAc 1406:1413 arg1 OsOGTs 1429:1434 OsOGTs 1429:1434 OsOGTs 1429:1434 Furthermore, we discovered two O-GlcNAc transferases (OsOGTs) in rice. 36577688 2 63 theme proteins 258:265 arg1 Thousands 245:253 Thousands 245:253 Thousands of proteins along with their O-GlcNAcylation sites 245:304 Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. 36577688 6 64 theme O-GlcNAcylated 1007:1020 arg1 proteins 1022:1029 709 O-GlcNAcylated proteins 1003:1029 709 O-GlcNAcylated proteins 1003:1029 A total of 1,591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins were identified. 36577688 7 65 theme located 1139:1145 arg1 sites 1133:1137 their O-GlcNAcylation sites 1111:1137 their O-GlcNAcylation sites located within a serine/threonine-enriched peptide, causing ambiguous site assignment 1111:1223 Additionally, 102 O-GlcNAcylated proteins were identified with their O-GlcNAcylation sites located within a serine/threonine-enriched peptide, causing ambiguous site assignment. 36577688 11 66 from biology 1699:1705 arg1 rice 1710:1713 rice 1710:1713 rice 1710:1713 Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants. 36577688 3 67 from profiling 453:461 arg1 manner 509:514 a site-specific manner 493:514 a site-specific manner in rice 493:522 Here, we report a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice. 36577688 7 68 theme O-GlcNAcylation 1117:1131 arg1 sites 1133:1137 their O-GlcNAcylation sites 1111:1137 their O-GlcNAcylation sites located within a serine/threonine-enriched peptide, causing ambiguous site assignment 1111:1223 Additionally, 102 O-GlcNAcylated proteins were identified with their O-GlcNAcylation sites located within a serine/threonine-enriched peptide, causing ambiguous site assignment. 36577688 11 69 theme O-GlcNAcylated 1775:1788 arg1 proteins 1790:1797 O-GlcNAcylated proteins 1775:1797 O-GlcNAcylated proteins in various plants 1775:1815 Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants. 36577688 2 70 theme O-GlcNAcylated 362:375 arg1 proteomes 377:385 the O-GlcNAcylated proteomes 358:385 the O-GlcNAcylated proteomes in plants 358:395 Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. 36577688 10 71 theme Nicotiana 1491:1499 arg1 benthamiana 1501:1511 Nicotiana benthamiana 1491:1511 Nicotiana benthamiana 1491:1511 By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. 36577688 0 72 theme transferases 83:94 arg1 identification 56:69 identification 56:69 identification of O-GlcNAc transferases in rice 56:102 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 0 72 theme transferases 83:94 arg1 profiling 15:23 Chemoproteomic profiling 0:23 Chemoproteomic profiling of O-GlcNAcylated proteins 0:50 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 2 73 theme sites 300:304 arg1 Thousands 245:253 Thousands 245:253 Thousands of proteins along with their O-GlcNAcylation sites 245:304 Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. 36577688 4 74 theme azides 682:687 arg1 handle 708:713 a bioorthogonal handle 692:713 a bioorthogonal handle into O-GlcNAc 692:727 We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. 36577688 4 74 theme azides 682:687 arg1 incorporation 665:677 incorporation 665:677 incorporation of azides 665:687 We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. 36577688 1 75 theme ubiquitous 165:174 arg1 β-N-acetylglucosaminylation 114:140 O-linked β-N-acetylglucosaminylation 105:140 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 105:158 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. 36577688 1 75 theme ubiquitous 165:174 arg1 modification 194:205 a ubiquitous posttranslational modification 163:205 a ubiquitous posttranslational modification occurring in both animals and plants 163:242 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. 36577688 6 76 theme sites 982:986 arg1 total 939:943 A total 937:943 A total of 1,591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins 937:1029 A total of 1,591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins were identified. 36577688 0 77 theme O-GlcNAc 74:81 arg1 transferases 83:94 O-GlcNAc transferases 74:94 O-GlcNAc transferases in rice 74:102 Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice. 36577688 4 78 theme metabolic 550:558 arg1 labeling 567:574 metabolic glycan labeling 550:574 the metabolic glycan labeling strategy (MGL) 546:589 We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. 36577688 2 79 theme O-GlcNAcylation 284:298 arg1 sites 300:304 their O-GlcNAcylation sites 278:304 proteins along with their O-GlcNAcylation sites 258:304 Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. 36577688 7 80 theme O-GlcNAcylated 1066:1079 arg1 proteins 1081:1088 102 O-GlcNAcylated proteins 1062:1088 102 O-GlcNAcylated proteins 1062:1088 Additionally, 102 O-GlcNAcylated proteins were identified with their O-GlcNAcylation sites located within a serine/threonine-enriched peptide, causing ambiguous site assignment. 36577688 1 81 theme posttranslational 176:192 arg1 β-N-acetylglucosaminylation 114:140 O-linked β-N-acetylglucosaminylation 105:140 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 105:158 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. 36577688 1 81 theme posttranslational 176:192 arg1 modification 194:205 a ubiquitous posttranslational modification 163:205 a ubiquitous posttranslational modification occurring in both animals and plants 163:242 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. 36531508 3 0 theme fetal 549:553 arg1 growth 555:560 fetal growth 549:560 fetal growth 549:560 However, it is unclear how protein O-GlcNAcylation affects placental function and fetal growth throughout pregnancy during hypertension. 36531508 15 1 theme hypertensive 2222:2233 arg1 pregnancy 2235:2243 hypertensive pregnancy 2222:2243 hypertensive pregnancy 2222:2243 Conclusions These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth. 36531508 13 2 theme decreased 1878:1886 arg1 content 1902:1908 decreased glycogen cell content 1878:1908 decreased glycogen cell content in the placentas from SHR 1878:1934 Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. 36531508 15 3 theme protein 2102:2108 arg1 O-GlcNAcylation 2110:2124 decreased protein O-GlcNAcylation 2092:2124 decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport 2092:2176 Conclusions These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth. 36531508 10 4 theme O-GlcNAc 1487:1494 arg1 expression 1504:1513 O-GlcNAc protein expression 1487:1513 O-GlcNAc protein expression 1487:1513 O-GlcNAc protein expression was lower in placentas from SHR compared with Wistar at 14, 17, and 20 DOPs. 36531508 15 5 dep Conclusions 2052:2062 arg1 suggest 2079:2085 suggest 2079:2085 suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth 2079:2267 Conclusions These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth. 36531508 4 6 theme Wistar 719:724 arg1 rats 726:729 male Wistar rats 714:729 male Wistar rats 714:729 Methods To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). 36531508 13 7 theme Periodic 1841:1848 arg1 acid-Schiff 1850:1860 Periodic acid-Schiff 1841:1860 Periodic acid-Schiff analysis 1841:1869 Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. 36531508 8 8 dep 17 1312:1313 arg1 DOPs 1331:1334 DOPs 1331:1334 DOPs 1331:1334 While near-term placentas were heavier in SHR (p=0.006), placental efficiency decreased at 17 (p=0.01) and 20 DOPs (p<0.0001) in this group. 36531508 2 9 theme abnormal 369:376 arg1 O-GlcNAcylation 386:400 abnormal protein O-GlcNAcylation 369:400 abnormal protein O-GlcNAcylation 369:400 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 9 10 theme reduced 1394:1400 arg1 area 1418:1421 reduced junctional zone area 1394:1421 reduced junctional zone area 1394:1421 Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. 36531508 12 11 from content 1764:1770 arg1 labyrinth 1804:1812 labyrinth 1804:1812 labyrinth 1804:1812 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 12 11 from content 1764:1770 arg1 zone 1795:1798 the junctional zone 1780:1798 the junctional zone 1780:1798 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 2 12 theme Important 235:243 arg1 proteins 245:252 Important proteins 235:252 Important proteins during placentation 235:272 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 9 13 theme zone 1413:1416 arg1 area 1418:1421 reduced junctional zone area 1394:1421 reduced junctional zone area 1394:1421 Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. 36531508 0 14 from dysfunction 65:75 arg1 pregnancy 93:101 hypertensive pregnancy 80:101 hypertensive pregnancy 80:101 Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy. 36531508 6 15 theme blood 1071:1075 arg1 pressure 1077:1084 a higher blood pressure 1062:1084 a higher blood pressure 1062:1084 Results SHR presented a higher blood pressure than the Wistar rats (p=0.001). 36531508 1 16 theme arterial 135:142 arg1 hypertension 144:155 arterial hypertension 135:155 arterial hypertension 135:155 Introduction During pregnancy, arterial hypertension may impair placental function, which is critical for a healthy baby's growth. 36531508 7 17 from weight 1160:1165 arg1 fetuses 1212:1218 small-for-gestational-age fetuses 1186:1218 small-for-gestational-age fetuses 1186:1218 Across all DOPs, SHR showed reduced fetal weight and an increase in small-for-gestational-age fetuses. 36531508 4 18 theme vaginal 768:774 arg1 smear 776:780 vaginal smear 768:780 vaginal smear 768:780 Methods To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). 36531508 11 19 theme O-GlcNAcase 1650:1660 arg1 enzymes 1672:1678 O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes 1616:1678 O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes 1616:1678 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. 36531508 9 20 theme vasculature 1437:1447 arg1 changes 1449:1455 reduced junctional zone area and labyrinth vasculature changes 1394:1455 reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs 1394:1484 Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. 36531508 1 21 theme placental 168:176 arg1 function 178:185 placental function 168:185 placental function 168:185 Introduction During pregnancy, arterial hypertension may impair placental function, which is critical for a healthy baby's growth. 36531508 11 22 theme enzymes 1672:1678 arg1 expression 1602:1611 Decreased expression 1592:1611 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes 1592:1678 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. 36531508 0 23 theme hypertensive 80:91 arg1 pregnancy 93:101 hypertensive pregnancy 80:101 hypertensive pregnancy 80:101 Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy. 36531508 7 24 theme reduced 1146:1152 arg1 weight 1160:1165 reduced fetal weight 1146:1165 reduced fetal weight 1146:1165 Across all DOPs, SHR showed reduced fetal weight and an increase in small-for-gestational-age fetuses. 36531508 12 25 theme placentas 1821:1829 arg1 labyrinth 1804:1812 labyrinth 1804:1812 labyrinth 1804:1812 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 12 25 theme placentas 1821:1829 arg1 zone 1795:1798 the junctional zone 1780:1798 the junctional zone 1780:1798 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 15 26 theme decreased 2092:2100 arg1 O-GlcNAcylation 2110:2124 decreased protein O-GlcNAcylation 2092:2124 decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport 2092:2176 Conclusions These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth. 36531508 14 27 theme transporter 1978:1988 arg1 expression 1992:2001 glucose transporter 1 expression 1970:2001 glucose transporter 1 expression 1970:2001 Moreover, glucose transporter 1 expression was decreased in placentas from SHR in all DOPs. 36531508 2 28 theme pathological 421:432 arg1 conditions 434:443 pathological conditions 421:443 pathological conditions such as hypertension 421:464 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 2 28 theme pathological 421:432 arg1 hypertension 453:464 hypertension 453:464 hypertension 453:464 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 12 29 theme junctional 1784:1793 arg1 zone 1795:1798 the junctional zone 1780:1798 the junctional zone 1780:1798 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 6 30 theme Results 1040:1046 arg1 SHR 1048:1050 Results SHR 1040:1050 Results SHR 1040:1050 Results SHR presented a higher blood pressure than the Wistar rats (p=0.001). 36531508 10 31 from SHR 1543:1545 arg1 placentas 1528:1536 placentas 1528:1536 placentas from SHR 1528:1545 O-GlcNAc protein expression was lower in placentas from SHR compared with Wistar at 14, 17, and 20 DOPs. 36531508 0 32 theme Protein 0:6 arg1 O-GlcNAcylation 8:22 Protein O-GlcNAcylation 0:22 Protein O-GlcNAcylation as a nutrient sensor 0:43 Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy. 36531508 15 33 theme nutritional 2159:2169 arg1 apport 2171:2176 insufficient placental nutritional apport 2136:2176 insufficient placental nutritional apport 2136:2176 Conclusions These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth. 36531508 5 34 theme fetal 912:916 arg1 parameters 918:927 fetal parameters 912:927 fetal parameters 912:927 On the 14th, 17th, and 20th DOP, rats were euthanized, fetal parameters were measured, and placentas were collected for western blot, immunohistochemical, and morphological analyses. 36531508 0 35 theme nutrient 29:36 arg1 sensor 38:43 a nutrient sensor 27:43 a nutrient sensor 27:43 Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy. 36531508 15 36 theme insufficient 2136:2147 arg1 apport 2171:2176 insufficient placental nutritional apport 2136:2176 insufficient placental nutritional apport 2136:2176 Conclusions These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth. 36531508 5 37 theme western 977:983 arg1 blot 985:988 western blot 977:988 western blot 977:988 On the 14th, 17th, and 20th DOP, rats were euthanized, fetal parameters were measured, and placentas were collected for western blot, immunohistochemical, and morphological analyses. 36531508 11 38 theme Decreased 1592:1600 arg1 expression 1602:1611 Decreased expression 1592:1611 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes 1592:1678 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. 36531508 3 39 theme placental 526:534 arg1 function 536:543 placental function 526:543 placental function 526:543 However, it is unclear how protein O-GlcNAcylation affects placental function and fetal growth throughout pregnancy during hypertension. 36531508 12 40 theme placental 1745:1753 arg1 content 1764:1770 reduced placental O-GlcNAc content 1737:1770 reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR 1737:1838 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 11 41 theme transferase 1625:1635 arg1 enzymes 1672:1678 O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes 1616:1678 O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes 1616:1678 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. 36531508 6 42 theme higher 1064:1069 arg1 pressure 1077:1084 a higher blood pressure 1062:1084 a higher blood pressure 1062:1084 Results SHR presented a higher blood pressure than the Wistar rats (p=0.001). 36531508 4 43 theme hypertensive 674:685 arg1 SHR 693:695 SHR 693:695 SHR 693:695 Methods To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). 36531508 4 43 theme hypertensive 674:685 arg1 rats 687:690 spontaneously hypertensive rats 660:690 spontaneously hypertensive rats (SHR) 660:696 Methods To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). 36531508 2 44 theme protein 378:384 arg1 O-GlcNAcylation 386:400 abnormal protein O-GlcNAcylation 369:400 abnormal protein O-GlcNAcylation 369:400 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 7 45 from increase 1174:1181 arg1 fetuses 1212:1218 small-for-gestational-age fetuses 1186:1218 small-for-gestational-age fetuses 1186:1218 Across all DOPs, SHR showed reduced fetal weight and an increase in small-for-gestational-age fetuses. 36531508 15 46 theme placental 2193:2201 arg1 dysfunction 2203:2213 placental dysfunction 2193:2213 placental dysfunction 2193:2213 Conclusions These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth. 36531508 9 47 from changes 1449:1455 arg1 DOPs 1481:1484 all DOPs 1477:1484 all DOPs 1477:1484 Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. 36531508 9 47 from changes 1449:1455 arg1 placentas 1464:1472 SHR placentas 1460:1472 SHR placentas 1460:1472 Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. 36531508 4 48 theme female 642:647 arg1 Wistar 649:654 female Wistar 642:654 female Wistar 642:654 Methods To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). 36531508 10 49 theme protein 1496:1502 arg1 expression 1504:1513 O-GlcNAc protein expression 1487:1513 O-GlcNAc protein expression 1487:1513 O-GlcNAc protein expression was lower in placentas from SHR compared with Wistar at 14, 17, and 20 DOPs. 36531508 13 50 theme glycogen 1888:1895 arg1 content 1902:1908 decreased glycogen cell content 1878:1908 decreased glycogen cell content in the placentas from SHR 1878:1934 Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. 36531508 4 51 theme pregnancy 839:847 arg1 days 831:834 14, 17, and 20 days 816:834 14, 17, and 20 days of pregnancy (DOPs) 816:854 Methods To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). 36531508 9 52 theme Morphological 1362:1374 arg1 analysis 1376:1383 Morphological analysis 1362:1383 Morphological analysis 1362:1383 Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. 36531508 11 53 from DOPs 1696:1699 arg1 SHR 1704:1706 SHR 1704:1706 SHR 1704:1706 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. 36531508 4 54 theme male 714:717 arg1 rats 726:729 male Wistar rats 714:729 male Wistar rats 714:729 Methods To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). 36531508 11 55 located found 1684:1688 arg1 DOPs 1696:1699 14 DOPs 1693:1699 14 DOPs in SHR 1693:1706 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. 36531508 11 55 located found 1684:1688 arg2 expression 1602:1611 Decreased expression 1592:1611 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes 1592:1678 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. 36531508 2 56 theme β-N-acetylglucosamine 311:331 arg1 O-GlcNAcylation 347:361 O-GlcNAcylation 347:361 O-GlcNAcylation 347:361 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 2 56 theme β-N-acetylglucosamine 311:331 arg1 modification 333:344 O-linked β-N-acetylglucosamine modification 302:344 O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) 302:362 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 13 57 from SHR 1932:1934 arg1 content 1902:1908 decreased glycogen cell content 1878:1908 decreased glycogen cell content in the placentas from SHR 1878:1934 Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. 36531508 13 57 from SHR 1932:1934 arg1 placentas 1917:1925 the placentas 1913:1925 the placentas from SHR 1913:1934 Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. 36531508 13 58 from content 1902:1908 arg1 SHR 1932:1934 SHR 1932:1934 SHR 1932:1934 Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. 36531508 13 58 from content 1902:1908 arg1 placentas 1917:1925 the placentas 1913:1925 the placentas from SHR 1913:1934 Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. 36531508 9 59 theme junctional 1402:1411 arg1 area 1418:1421 reduced junctional zone area 1394:1421 reduced junctional zone area 1394:1421 Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. 36531508 8 60 theme near-term 1227:1235 arg1 placentas 1237:1245 near-term placentas 1227:1245 near-term placentas 1227:1245 While near-term placentas were heavier in SHR (p=0.006), placental efficiency decreased at 17 (p=0.01) and 20 DOPs (p<0.0001) in this group. 36531508 2 61 link O-linked 302:309 arg1 O-GlcNAcylation 347:361 O-GlcNAcylation 347:361 O-GlcNAcylation 347:361 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 2 61 link O-linked 302:309 arg1 modification 333:344 O-linked β-N-acetylglucosamine modification 302:344 O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) 302:362 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 9 62 theme area 1418:1421 arg1 changes 1449:1455 reduced junctional zone area and labyrinth vasculature changes 1394:1455 reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs 1394:1484 Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. 36531508 14 63 from SHR 2035:2037 arg1 placentas 2020:2028 placentas 2020:2028 placentas from SHR 2020:2037 Moreover, glucose transporter 1 expression was decreased in placentas from SHR in all DOPs. 36531508 4 64 theme pregnancy 742:750 arg1 confirmation 752:763 pregnancy confirmation 742:763 pregnancy confirmation by vaginal smear 742:780 Methods To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). 36531508 13 65 theme acid-Schiff 1850:1860 arg1 analysis 1862:1869 Periodic acid-Schiff analysis 1841:1869 Periodic acid-Schiff analysis 1841:1869 Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. 36531508 9 66 theme labyrinth 1427:1435 arg1 vasculature 1437:1447 labyrinth vasculature 1427:1447 labyrinth vasculature 1427:1447 Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. 36531508 5 67 theme morphological 1016:1028 arg1 analyses 1030:1037 morphological analyses 1016:1037 morphological analyses 1016:1037 On the 14th, 17th, and 20th DOP, rats were euthanized, fetal parameters were measured, and placentas were collected for western blot, immunohistochemical, and morphological analyses. 36531508 7 68 theme fetal 1154:1158 arg1 weight 1160:1165 reduced fetal weight 1146:1165 reduced fetal weight 1146:1165 Across all DOPs, SHR showed reduced fetal weight and an increase in small-for-gestational-age fetuses. 36531508 9 69 theme SHR 1460:1462 arg1 placentas 1464:1472 SHR placentas 1460:1472 SHR placentas 1460:1472 Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. 36531508 12 70 from labyrinth 1804:1812 arg1 SHR 1836:1838 SHR 1836:1838 SHR 1836:1838 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 2 71 theme O-linked 302:309 arg1 O-GlcNAcylation 347:361 O-GlcNAcylation 347:361 O-GlcNAcylation 347:361 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 2 71 theme O-linked 302:309 arg1 modification 333:344 O-linked β-N-acetylglucosamine modification 302:344 O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) 302:362 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 12 72 from zone 1795:1798 arg1 SHR 1836:1838 SHR 1836:1838 SHR 1836:1838 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 8 73 theme placental 1278:1286 arg1 efficiency 1288:1297 placental efficiency 1278:1297 placental efficiency 1278:1297 While near-term placentas were heavier in SHR (p=0.006), placental efficiency decreased at 17 (p=0.01) and 20 DOPs (p<0.0001) in this group. 36531508 1 74 theme healthy 212:218 arg1 baby 220:223 a healthy baby 210:223 a healthy baby's growth 210:232 Introduction During pregnancy, arterial hypertension may impair placental function, which is critical for a healthy baby's growth. 36531508 14 75 theme glucose 1970:1976 arg1 transporter 1978:1988 glucose transporter 1 1970:1990 glucose transporter 1 expression 1970:2001 Moreover, glucose transporter 1 expression was decreased in placentas from SHR in all DOPs. 36531508 2 76 attach linked 411:416 arg2 O-GlcNAcylation 386:400 abnormal protein O-GlcNAcylation 369:400 abnormal protein O-GlcNAcylation 369:400 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 2 76 attach linked 411:416 arg1 conditions 434:443 pathological conditions 421:443 pathological conditions such as hypertension 421:464 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 2 76 attach linked 411:416 arg1 hypertension 453:464 hypertension 453:464 hypertension 453:464 Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. 36531508 3 77 theme protein 494:500 arg1 O-GlcNAcylation 502:516 protein O-GlcNAcylation 494:516 protein O-GlcNAcylation 494:516 However, it is unclear how protein O-GlcNAcylation affects placental function and fetal growth throughout pregnancy during hypertension. 36531508 0 78 theme placental 55:63 arg1 dysfunction 65:75 placental dysfunction 55:75 placental dysfunction in hypertensive pregnancy 55:101 Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy. 36531508 15 79 theme placental 2149:2157 arg1 apport 2171:2176 insufficient placental nutritional apport 2136:2176 insufficient placental nutritional apport 2136:2176 Conclusions These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth. 36531508 12 80 theme reduced 1737:1743 arg1 content 1764:1770 reduced placental O-GlcNAc content 1737:1770 reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR 1737:1838 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 6 81 theme Wistar 1095:1100 arg1 p=0.001 1108:1114 p=0.001 1108:1114 p=0.001 1108:1114 Results SHR presented a higher blood pressure than the Wistar rats (p=0.001). 36531508 6 81 theme Wistar 1095:1100 arg1 rats 1102:1105 the Wistar rats 1091:1105 the Wistar rats (p=0.001) 1091:1115 Results SHR presented a higher blood pressure than the Wistar rats (p=0.001). 36531508 4 82 theme days 831:834 arg1 days 831:834 14, 17, and 20 days 816:834 14, 17, and 20 days of pregnancy (DOPs) 816:854 Methods To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). 36531508 4 82 theme days 831:834 arg1 groups 806:811 groups 806:811 groups of 14, 17, and 20 days of pregnancy (DOPs) 806:854 Methods To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). 36531508 12 83 theme O-GlcNAc 1755:1762 arg1 content 1764:1770 reduced placental O-GlcNAc content 1737:1770 reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR 1737:1838 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 11 84 theme O-GlcNAc 1616:1623 arg1 transferase 1625:1635 O-GlcNAc transferase 1616:1635 O-GlcNAc transferase (p=0.01) 1616:1644 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. 36531508 11 84 theme O-GlcNAc 1616:1623 arg1 p=0.01 1638:1643 p=0.01 1638:1643 p=0.01 1638:1643 Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. 36531508 13 85 theme cell 1897:1900 arg1 content 1902:1908 decreased glycogen cell content 1878:1908 decreased glycogen cell content in the placentas from SHR 1878:1934 Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. 36531508 15 86 theme fetal 2256:2260 arg1 growth 2262:2267 fetal growth 2256:2267 fetal growth 2256:2267 Conclusions These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth. 36531508 12 87 from SHR 1836:1838 arg1 labyrinth 1804:1812 labyrinth 1804:1812 labyrinth 1804:1812 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 12 87 from SHR 1836:1838 arg1 placentas 1821:1829 the placentas 1817:1829 the placentas from SHR 1817:1838 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 12 87 from SHR 1836:1838 arg1 zone 1795:1798 the junctional zone 1780:1798 the junctional zone 1780:1798 Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. 36531508 7 88 theme small-for-gestational-age 1186:1210 arg1 fetuses 1212:1218 small-for-gestational-age fetuses 1186:1218 small-for-gestational-age fetuses 1186:1218 Across all DOPs, SHR showed reduced fetal weight and an increase in small-for-gestational-age fetuses. 35398365 3 0 theme fibers 688:693 arg1 characterization 645:660 the structural characterization 630:660 the structural characterization of the fibroin-based silk fibers produced by the ant 630:713 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 3 1 theme nuclear 495:501 arg1 NMR 523:525 NMR 523:525 NMR 523:525 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 3 1 theme nuclear 495:501 arg1 resonance 512:520 nuclear magnetic resonance 495:520 nuclear magnetic resonance (NMR) spectroscopy 495:539 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 6 2 from units 1064:1068 arg1 model 1083:1087 the whole model 1073:1087 the whole model 1073:1087 The 3D of protein was modeled, revealing a structure predominantly constituted of coiled-coil secondary units in the whole model, featuring at least four superhelices (arrangement with multiple α-helices). 35398365 3 3 theme spectroscopy 528:539 arg1 series 464:469 a series 462:469 a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant 462:713 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 6 4 theme multiple 1145:1152 arg1 α-helices 1154:1162 multiple α-helices 1145:1162 multiple α-helices 1145:1162 The 3D of protein was modeled, revealing a structure predominantly constituted of coiled-coil secondary units in the whole model, featuring at least four superhelices (arrangement with multiple α-helices). 35398365 6 5 dep superhelices 1114:1125 arg1 arrangement 1128:1138 arrangement 1128:1138 arrangement 1128:1138 The 3D of protein was modeled, revealing a structure predominantly constituted of coiled-coil secondary units in the whole model, featuring at least four superhelices (arrangement with multiple α-helices). 35398365 2 6 theme silk 270:273 arg1 fibers 275:280 the silk fibers 266:280 the silk fibers from the nest of the weaver ant Camponotus textor 266:330 In this context, the silk fibers from the nest of the weaver ant Camponotus textor was solubilized and fractionated by gel permeation. 35398365 3 7 with methods 486:492 arg1 tools 613:617 bioinformatic tools 599:617 bioinformatic tools 599:617 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 3 8 theme strategies 563:572 arg1 series 464:469 a series 462:469 a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant 462:713 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 3 9 with analysis 448:455 arg1 series 464:469 a series 462:469 a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant 462:713 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 3 10 theme analytical 542:551 arg1 strategies 563:572 analytical proteomic strategies 542:572 analytical proteomic strategies 542:572 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 3 11 theme treatment 584:592 arg1 series 464:469 a series 462:469 a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant 462:713 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 1 12 theme potential 214:222 arg1 applications 235:246 potential biomedical applications 214:246 potential biomedical applications 214:246 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 8 13 theme silk 1479:1482 arg1 fibers 1484:1489 the fibroin-based silk fibers 1461:1489 the fibroin-based silk fibers from weaver ants 1461:1506 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 10 14 theme new 1793:1795 arg1 insights 1797:1804 new insights 1793:1804 new insights into the secondary structures considering the whole model of the protein 1793:1877 Moreover, the 3D structure provided new insights into the secondary structures considering the whole model of the protein. 35398365 7 15 theme biomedical 1339:1348 arg1 applications 1350:1361 biomedical applications 1339:1361 biomedical applications 1339:1361 The scientific outcomes reported herein may be relevant for the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications. 35398365 5 16 theme total 900:904 arg1 sugars 906:911 total sugars 900:911 total sugars attached to it through O-linked carbohydrates 900:957 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 7 17 theme polymers 1326:1333 arg1 production 1295:1304 the synthetic or recombinant production 1266:1304 the synthetic or recombinant production of novel silk-based polymers for biomedical applications 1266:1361 The scientific outcomes reported herein may be relevant for the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications. 35398365 3 18 theme bioinformatic 599:611 arg1 tools 613:617 bioinformatic tools 599:617 bioinformatic tools 599:617 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 0 19 theme ant 79:81 arg1 textor 94:99 weaver ant Camponotus textor 72:99 weaver ant Camponotus textor 72:99 Proteomic characterization of the fibroin-based silk fibers produced by weaver ant Camponotus textor. 35398365 1 20 theme alternative 154:164 arg1 biomaterial 166:176 an alternative biomaterial 151:176 an alternative biomaterial to be investigated and explored for potential biomedical applications 151:246 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 1 20 theme alternative 154:164 arg1 fibers 125:130 The fibroin-based silk fibers 102:130 The fibroin-based silk fibers of weaver ants 102:145 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 10 21 theme secondary 1815:1823 arg1 structures 1825:1834 the secondary structures 1811:1834 the secondary structures considering the whole model of the protein 1811:1877 Moreover, the 3D structure provided new insights into the secondary structures considering the whole model of the protein. 35398365 4 22 theme fibroin 764:770 arg1 proteoform 772:781 one fibroin proteoform 760:781 one fibroin proteoform 760:781 Our data demonstrated the identification of one fibroin proteoform in the ant silk fibers. 35398365 8 23 from ants 1503:1506 arg1 fibers 1484:1489 the fibroin-based silk fibers 1461:1489 the fibroin-based silk fibers from weaver ants 1461:1506 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 5 24 theme O-linked 936:943 arg1 carbohydrates 945:957 O-linked carbohydrates 936:957 O-linked carbohydrates 936:957 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 8 25 dep expanded 1429:1436 arg1 SIGNIFICANCE 1375:1386 BIOLOGICAL SIGNIFICANCE 1364:1386 BIOLOGICAL SIGNIFICANCE 1364:1386 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 3 26 with treatment 584:592 arg1 tools 613:617 bioinformatic tools 599:617 bioinformatic tools 599:617 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 6 27 theme secondary 1054:1062 arg1 units 1064:1068 coiled-coil secondary units 1042:1068 coiled-coil secondary units in the whole model, featuring at least four superhelices (arrangement with multiple α-helices) 1042:1163 The 3D of protein was modeled, revealing a structure predominantly constituted of coiled-coil secondary units in the whole model, featuring at least four superhelices (arrangement with multiple α-helices). 35398365 1 28 theme weaver 135:140 arg1 ants 142:145 weaver ants 135:145 weaver ants 135:145 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 8 29 theme BIOLOGICAL 1364:1373 arg1 SIGNIFICANCE 1375:1386 BIOLOGICAL SIGNIFICANCE 1364:1386 BIOLOGICAL SIGNIFICANCE 1364:1386 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 8 30 from improvements 1525:1536 arg1 understanding 1545:1557 our understanding 1541:1557 our understanding of the properties and characteristics of these silk fibers 1541:1616 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 8 31 theme properties 1566:1575 arg1 understanding 1545:1557 our understanding 1541:1557 our understanding of the properties and characteristics of these silk fibers 1541:1616 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 5 32 with glycoprotein 837:848 arg1 MW 855:856 MW 855:856 MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates 855:957 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 3 33 with strategies 563:572 arg1 tools 613:617 bioinformatic tools 599:617 bioinformatic tools 599:617 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 1 34 theme fibroin-based 106:118 arg1 biomaterial 166:176 an alternative biomaterial 151:176 an alternative biomaterial to be investigated and explored for potential biomedical applications 151:246 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 1 34 theme fibroin-based 106:118 arg1 fibers 125:130 The fibroin-based silk fibers 102:130 The fibroin-based silk fibers of weaver ants 102:145 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 7 35 theme recombinant 1283:1293 arg1 production 1295:1304 the synthetic or recombinant production 1266:1304 the synthetic or recombinant production of novel silk-based polymers for biomedical applications 1266:1361 The scientific outcomes reported herein may be relevant for the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications. 35398365 8 36 theme characteristics 1581:1595 arg1 understanding 1545:1557 our understanding 1541:1557 our understanding of the properties and characteristics of these silk fibers 1541:1616 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 8 37 theme present 1393:1399 arg1 investigation 1401:1413 The present investigation 1389:1413 The present investigation 1389:1413 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 0 38 theme fibroin-based 34:46 arg1 fibers 53:58 the fibroin-based silk fibers 30:58 the fibroin-based silk fibers 30:58 Proteomic characterization of the fibroin-based silk fibers produced by weaver ant Camponotus textor. 35398365 7 39 theme synthetic 1270:1278 arg1 production 1295:1304 the synthetic or recombinant production 1266:1304 the synthetic or recombinant production of novel silk-based polymers for biomedical applications 1266:1361 The scientific outcomes reported herein may be relevant for the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications. 35398365 3 40 theme different 388:396 arg1 fractions 398:406 The different fractions 384:406 The different fractions 384:406 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 10 41 theme whole 1852:1856 arg1 model 1858:1862 the whole model 1848:1862 the whole model of the protein 1848:1877 Moreover, the 3D structure provided new insights into the secondary structures considering the whole model of the protein. 35398365 3 42 theme biochemical 474:484 arg1 methods 486:492 biochemical methods 474:492 biochemical methods 474:492 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 3 43 with spectroscopy 528:539 arg1 tools 613:617 bioinformatic tools 599:617 bioinformatic tools 599:617 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 8 44 theme fibers 1611:1616 arg1 characteristics 1581:1595 characteristics 1581:1595 characteristics 1581:1595 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 8 44 theme fibers 1611:1616 arg1 properties 1566:1575 properties 1566:1575 properties 1566:1575 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 3 45 theme silk 683:686 arg1 fibers 688:693 the fibroin-based silk fibers 665:693 the fibroin-based silk fibers produced by the ant 665:713 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 4 46 theme ant 790:792 arg1 fibers 799:804 the ant silk fibers 786:804 the ant silk fibers 786:804 Our data demonstrated the identification of one fibroin proteoform in the ant silk fibers. 35398365 2 47 theme Camponotus 314:323 arg1 textor 325:330 the weaver ant Camponotus textor 299:330 the weaver ant Camponotus textor 299:330 In this context, the silk fibers from the nest of the weaver ant Camponotus textor was solubilized and fractionated by gel permeation. 35398365 1 48 theme biomedical 224:233 arg1 applications 235:246 potential biomedical applications 214:246 potential biomedical applications 214:246 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 7 49 theme novel 1245:1249 arg1 approaches 1251:1260 novel approaches 1245:1260 novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications 1245:1361 The scientific outcomes reported herein may be relevant for the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications. 35398365 10 50 theme protein 1871:1877 arg1 model 1858:1862 the whole model 1848:1862 the whole model of the protein 1848:1877 Moreover, the 3D structure provided new insights into the secondary structures considering the whole model of the protein. 35398365 3 51 theme magnetic 503:510 arg1 NMR 523:525 NMR 523:525 NMR 523:525 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 3 51 theme magnetic 503:510 arg1 resonance 512:520 nuclear magnetic resonance 495:520 nuclear magnetic resonance (NMR) spectroscopy 495:539 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 6 52 theme whole 1077:1081 arg1 model 1083:1087 the whole model 1073:1087 the whole model 1073:1087 The 3D of protein was modeled, revealing a structure predominantly constituted of coiled-coil secondary units in the whole model, featuring at least four superhelices (arrangement with multiple α-helices). 35398365 2 53 theme weaver 303:308 arg1 textor 325:330 the weaver ant Camponotus textor 299:330 the weaver ant Camponotus textor 299:330 In this context, the silk fibers from the nest of the weaver ant Camponotus textor was solubilized and fractionated by gel permeation. 35398365 9 54 located detected 1669:1676 arg2 carbohydrates 1650:1662 carbohydrates 1650:1662 carbohydrates 1650:1662 For example, as reported here, carbohydrates were detected in the ants' silk for the first time presenting the fibroin as a glycoprotein. 35398365 9 54 located detected 1669:1676 arg1 silk 1691:1694 the ants' silk 1681:1694 the ants' silk for the first time presenting the fibroin as a glycoprotein 1681:1754 For example, as reported here, carbohydrates were detected in the ants' silk for the first time presenting the fibroin as a glycoprotein. 35398365 5 55 link O-linked 936:943 arg1 carbohydrates 945:957 O-linked carbohydrates 936:957 O-linked carbohydrates 936:957 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 3 56 theme proteomic 553:561 arg1 strategies 563:572 analytical proteomic strategies 542:572 analytical proteomic strategies 542:572 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 5 57 gly glycoprotein 837:848 arg1 glycoprotein 837:848 a glycoprotein 835:848 a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates 835:957 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 0 58 theme fibers 53:58 arg1 characterization 10:25 Proteomic characterization 0:25 Proteomic characterization of the fibroin-based silk fibers 0:58 Proteomic characterization of the fibroin-based silk fibers produced by weaver ant Camponotus textor. 35398365 10 59 theme 3D 1771:1772 arg1 structure 1774:1782 the 3D structure 1767:1782 the 3D structure 1767:1782 Moreover, the 3D structure provided new insights into the secondary structures considering the whole model of the protein. 35398365 9 60 theme first 1704:1708 arg1 time 1710:1713 the first time 1700:1713 the first time presenting the fibroin as a glycoprotein 1700:1754 For example, as reported here, carbohydrates were detected in the ants' silk for the first time presenting the fibroin as a glycoprotein. 35398365 8 61 theme fibroin-based 1465:1477 arg1 fibers 1484:1489 the fibroin-based silk fibers 1461:1489 the fibroin-based silk fibers from weaver ants 1461:1506 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 1 62 theme ants 142:145 arg1 biomaterial 166:176 an alternative biomaterial 151:176 an alternative biomaterial to be investigated and explored for potential biomedical applications 151:246 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 1 62 theme ants 142:145 arg1 fibers 125:130 The fibroin-based silk fibers 102:130 The fibroin-based silk fibers of weaver ants 102:145 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 2 63 theme textor 325:330 arg1 nest 291:294 the nest 287:294 the nest of the weaver ant Camponotus textor 287:330 In this context, the silk fibers from the nest of the weaver ant Camponotus textor was solubilized and fractionated by gel permeation. 35398365 3 64 theme data 579:582 arg1 treatment 584:592 data treatment 579:592 data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant 579:713 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 5 65 attach attached 913:920 arg2 sugars 906:911 total sugars 900:911 total sugars attached to it through O-linked carbohydrates 900:957 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 5 65 attach attached 913:920 arg1 it 925:926 it 925:926 it 925:926 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 9 66 gly glycoprotein 1743:1754 arg1 fibroin 1730:1736 the fibroin 1726:1736 the fibroin 1726:1736 For example, as reported here, carbohydrates were detected in the ants' silk for the first time presenting the fibroin as a glycoprotein. 35398365 9 66 gly glycoprotein 1743:1754 arg1 glycoprotein 1743:1754 a glycoprotein 1741:1754 a glycoprotein 1741:1754 For example, as reported here, carbohydrates were detected in the ants' silk for the first time presenting the fibroin as a glycoprotein. 35398365 1 67 theme silk 120:123 arg1 biomaterial 166:176 an alternative biomaterial 151:176 an alternative biomaterial to be investigated and explored for potential biomedical applications 151:246 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 1 67 theme silk 120:123 arg1 fibers 125:130 The fibroin-based silk fibers 102:130 The fibroin-based silk fibers of weaver ants 102:145 The fibroin-based silk fibers of weaver ants are an alternative biomaterial to be investigated and explored for potential biomedical applications. 35398365 6 68 with arrangement 1128:1138 arg1 α-helices 1154:1162 multiple α-helices 1145:1162 multiple α-helices 1145:1162 The 3D of protein was modeled, revealing a structure predominantly constituted of coiled-coil secondary units in the whole model, featuring at least four superhelices (arrangement with multiple α-helices). 35398365 8 69 theme weaver 1496:1501 arg1 ants 1503:1506 weaver ants 1496:1506 weaver ants 1496:1506 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 0 70 theme weaver 72:77 arg1 textor 94:99 weaver ant Camponotus textor 72:99 weaver ant Camponotus textor 72:99 Proteomic characterization of the fibroin-based silk fibers produced by weaver ant Camponotus textor. 35398365 8 71 dep properties 1566:1575 arg1 the 1562:1564 the 1562:1564 the 1562:1564 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 5 72 theme presenting 876:885 arg1 % 889:889 presenting 66% 876:889 presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates 876:957 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 5 72 theme presenting 876:885 arg1 sugars 906:911 total sugars 900:911 total sugars attached to it through O-linked carbohydrates 900:957 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 5 72 theme presenting 876:885 arg1 w/w 892:894 w/w 892:894 w/w 892:894 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 0 73 theme Camponotus 83:92 arg1 textor 94:99 weaver ant Camponotus textor 72:99 weaver ant Camponotus textor 72:99 Proteomic characterization of the fibroin-based silk fibers produced by weaver ant Camponotus textor. 35398365 2 74 from nest 291:294 arg1 fibers 275:280 the silk fibers 266:280 the silk fibers from the nest of the weaver ant Camponotus textor 266:330 In this context, the silk fibers from the nest of the weaver ant Camponotus textor was solubilized and fractionated by gel permeation. 35398365 6 75 theme protein 970:976 arg1 3D 964:965 The 3D 960:965 The 3D of protein 960:976 The 3D of protein was modeled, revealing a structure predominantly constituted of coiled-coil secondary units in the whole model, featuring at least four superhelices (arrangement with multiple α-helices). 35398365 7 76 theme scientific 1170:1179 arg1 relevant 1213:1220 relevant 1213:1220 relevant 1213:1220 The scientific outcomes reported herein may be relevant for the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications. 35398365 7 76 theme scientific 1170:1179 arg1 outcomes 1181:1188 The scientific outcomes 1166:1188 The scientific outcomes reported herein 1166:1204 The scientific outcomes reported herein may be relevant for the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications. 35398365 0 77 theme Proteomic 0:8 arg1 characterization 10:25 Proteomic characterization 0:25 Proteomic characterization of the fibroin-based silk fibers 0:58 Proteomic characterization of the fibroin-based silk fibers produced by weaver ant Camponotus textor. 35398365 7 78 theme novel 1309:1313 arg1 polymers 1326:1333 novel silk-based polymers 1309:1333 novel silk-based polymers for biomedical applications 1309:1361 The scientific outcomes reported herein may be relevant for the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications. 35398365 4 79 theme proteoform 772:781 arg1 identification 742:755 the identification 738:755 the identification of one fibroin proteoform in the ant silk fibers 738:804 Our data demonstrated the identification of one fibroin proteoform in the ant silk fibers. 35398365 4 80 from identification 742:755 arg1 fibers 799:804 the ant silk fibers 786:804 the ant silk fibers 786:804 Our data demonstrated the identification of one fibroin proteoform in the ant silk fibers. 35398365 5 81 theme sugars 906:911 arg1 % 889:889 presenting 66% 876:889 presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates 876:957 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 5 81 theme sugars 906:911 arg1 sugars 906:911 total sugars 900:911 total sugars attached to it through O-linked carbohydrates 900:957 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 5 81 theme sugars 906:911 arg1 40 kDa 865:870 40 kDa 865:870 40 kDa 865:870 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 5 81 theme sugars 906:911 arg1 w/w 892:894 w/w 892:894 w/w 892:894 The protein chracterized as a glycoprotein with MW around 40 kDa and presenting 66% (w/w) of total sugars attached to it through O-linked carbohydrates. 35398365 6 82 theme coiled-coil 1042:1052 arg1 units 1064:1068 coiled-coil secondary units 1042:1068 coiled-coil secondary units in the whole model, featuring at least four superhelices (arrangement with multiple α-helices) 1042:1163 The 3D of protein was modeled, revealing a structure predominantly constituted of coiled-coil secondary units in the whole model, featuring at least four superhelices (arrangement with multiple α-helices). 35398365 2 83 theme gel 368:370 arg1 permeation 372:381 gel permeation 368:381 gel permeation 368:381 In this context, the silk fibers from the nest of the weaver ant Camponotus textor was solubilized and fractionated by gel permeation. 35398365 3 84 theme structural 634:643 arg1 characterization 645:660 the structural characterization 630:660 the structural characterization of the fibroin-based silk fibers produced by the ant 630:713 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 0 85 theme silk 48:51 arg1 fibers 53:58 the fibroin-based silk fibers 30:58 the fibroin-based silk fibers 30:58 Proteomic characterization of the fibroin-based silk fibers produced by weaver ant Camponotus textor. 35398365 8 86 theme silk 1606:1609 arg1 fibers 1611:1616 these silk fibers 1600:1616 these silk fibers 1600:1616 BIOLOGICAL SIGNIFICANCE: The present investigation significantly expanded knowledge regarding to the fibroin-based silk fibers from weaver ants, contributing to improvements in our understanding of the properties and characteristics of these silk fibers. 35398365 7 87 theme approaches 1251:1260 arg1 development 1230:1240 the development 1226:1240 the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications 1226:1361 The scientific outcomes reported herein may be relevant for the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications. 35398365 3 88 theme fibroin-based 669:681 arg1 fibers 688:693 the fibroin-based silk fibers 665:693 the fibroin-based silk fibers produced by the ant 665:713 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 3 89 theme methods 486:492 arg1 series 464:469 a series 462:469 a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant 462:713 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35398365 2 90 theme ant 310:312 arg1 textor 325:330 the weaver ant Camponotus textor 299:330 the weaver ant Camponotus textor 299:330 In this context, the silk fibers from the nest of the weaver ant Camponotus textor was solubilized and fractionated by gel permeation. 35398365 7 91 theme silk-based 1315:1324 arg1 polymers 1326:1333 novel silk-based polymers 1309:1333 novel silk-based polymers for biomedical applications 1309:1361 The scientific outcomes reported herein may be relevant for the development of novel approaches for the synthetic or recombinant production of novel silk-based polymers for biomedical applications. 35398365 4 92 theme silk 794:797 arg1 fibers 799:804 the ant silk fibers 786:804 the ant silk fibers 786:804 Our data demonstrated the identification of one fibroin proteoform in the ant silk fibers. 35398365 3 93 theme resonance 512:520 arg1 spectroscopy 528:539 nuclear magnetic resonance (NMR) spectroscopy 495:539 nuclear magnetic resonance (NMR) spectroscopy 495:539 The different fractions were collected, pooled and submitted to analysis with a series of biochemical methods, nuclear magnetic resonance (NMR) spectroscopy, analytical proteomic strategies, and data treatment with bioinformatic tools to perform the structural characterization of the fibroin-based silk fibers produced by the ant. 35230102 4 0 from influence 571:579 arg1 stability 627:635 the thermodynamic stability 609:635 the thermodynamic stability of thousands of proteins in parallel 609:672 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 35230102 8 1 theme modification 1440:1451 arg1 impact 1418:1423 the impact 1414:1423 the impact of any protein modification on the meltome of 1414:1469 These results establish O-GlcNAc as a bidirectional regulator of protein stability and provide a blueprint for exploring the impact of any protein modification on the meltome of, in principle, any organism. 35230102 3 2 from interrogation 410:422 arg1 proteome 493:500 the proteome 489:500 the proteome 489:500 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 4 3 theme unbiased 524:531 arg1 approach 547:554 an unbiased proteome-wide approach 521:554 an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel 521:672 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 35230102 4 4 from parallel 665:672 arg1 thousands 640:648 thousands 640:648 thousands of proteins in parallel 640:672 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 35230102 8 5 from impact 1418:1423 arg1 meltome 1460:1466 the meltome 1456:1466 the meltome of 1456:1469 These results establish O-GlcNAc as a bidirectional regulator of protein stability and provide a blueprint for exploring the impact of any protein modification on the meltome of, in principle, any organism. 35230102 8 6 theme protein 1432:1438 arg1 modification 1440:1451 any protein modification 1428:1451 any protein modification 1428:1451 These results establish O-GlcNAc as a bidirectional regulator of protein stability and provide a blueprint for exploring the impact of any protein modification on the meltome of, in principle, any organism. 35230102 4 7 theme thousands 640:648 arg1 stability 627:635 the thermodynamic stability 609:635 the thermodynamic stability of thousands of proteins in parallel 609:672 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 35230102 1 8 theme Posttranslational 67:83 arg1 modifications 85:97 Posttranslational modifications 67:97 Posttranslational modifications 67:97 Posttranslational modifications alter the biophysical properties of proteins and thereby influence cellular physiology. 35230102 6 9 theme orthogonal 1059:1068 arg1 methods 1070:1076 orthogonal methods 1059:1076 orthogonal methods targeting specific proteins 1059:1104 Using this thermal proteomic profiling strategy, we identify a set of 72 proteins displaying O-GlcNAc-dependent thermostability and validate this approach using orthogonal methods targeting specific proteins. 35230102 3 10 theme global 403:408 arg1 interrogation 410:422 global interrogation 403:422 global interrogation of the biophysical effects of posttranslational modifications on the proteome 403:500 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 2 11 theme emerging 191:198 arg1 manner 200:205 One emerging manner 187:205 One emerging manner by which such modifications regulate protein functions 187:260 One emerging manner by which such modifications regulate protein functions is through their ability to perturb protein stability. 35230102 4 12 theme proteins 653:660 arg1 thousands 640:648 thousands 640:648 thousands of proteins in parallel 640:672 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 35230102 4 13 from thousands 640:648 arg1 parallel 665:672 parallel 665:672 parallel 665:672 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 35230102 0 14 theme O-GlcNAc-Dependent 39:56 arg1 Meltome 58:64 the O-GlcNAc-Dependent Meltome 35:64 the O-GlcNAc-Dependent Meltome 35:64 Thermal Proteome Profiling Reveals the O-GlcNAc-Dependent Meltome. 35230102 7 15 theme proteins 1165:1172 arg1 majority 1153:1160 the majority 1149:1160 the majority of proteins influenced by O-GlcNAc 1149:1195 These collective observations reveal that the majority of proteins influenced by O-GlcNAc are, surprisingly, destabilized by O-GlcNAc and cluster into distinct macromolecular complexes. 35230102 0 16 theme Thermal 0:6 arg1 Profiling 17:25 Thermal Proteome Profiling 0:25 Thermal Proteome Profiling 0:25 Thermal Proteome Profiling Reveals the O-GlcNAc-Dependent Meltome. 35230102 0 17 theme Proteome 8:15 arg1 Profiling 17:25 Thermal Proteome Profiling 0:25 Thermal Proteome Profiling 0:25 Thermal Proteome Profiling Reveals the O-GlcNAc-Dependent Meltome. 35230102 4 18 theme proteome-wide 533:545 arg1 approach 547:554 an unbiased proteome-wide approach 521:554 an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel 521:672 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 35230102 1 19 theme biophysical 109:119 arg1 properties 121:130 the biophysical properties 105:130 the biophysical properties of proteins 105:142 Posttranslational modifications alter the biophysical properties of proteins and thereby influence cellular physiology. 35230102 8 20 theme stability 1366:1374 arg1 regulator 1345:1353 a bidirectional regulator 1329:1353 a bidirectional regulator of protein stability 1329:1374 These results establish O-GlcNAc as a bidirectional regulator of protein stability and provide a blueprint for exploring the impact of any protein modification on the meltome of, in principle, any organism. 35230102 8 20 theme stability 1366:1374 arg1 O-GlcNAc 1317:1324 O-GlcNAc 1317:1324 O-GlcNAc 1317:1324 These results establish O-GlcNAc as a bidirectional regulator of protein stability and provide a blueprint for exploring the impact of any protein modification on the meltome of, in principle, any organism. 35230102 3 21 theme biophysical 431:441 arg1 effects 443:449 the biophysical effects 427:449 the biophysical effects of posttranslational modifications on the proteome 427:500 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 4 22 theme thermodynamic 613:625 arg1 stability 627:635 the thermodynamic stability 609:635 the thermodynamic stability of thousands of proteins in parallel 609:672 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 35230102 6 23 theme proteomic 917:925 arg1 strategy 937:944 this thermal proteomic profiling strategy 904:944 this thermal proteomic profiling strategy 904:944 Using this thermal proteomic profiling strategy, we identify a set of 72 proteins displaying O-GlcNAc-dependent thermostability and validate this approach using orthogonal methods targeting specific proteins. 35230102 5 24 theme select 862:867 arg1 cases 869:873 select cases 862:873 select cases 862:873 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 7 25 theme distinct 1258:1265 arg1 complexes 1282:1290 distinct macromolecular complexes 1258:1290 distinct macromolecular complexes 1258:1290 These collective observations reveal that the majority of proteins influenced by O-GlcNAc are, surprisingly, destabilized by O-GlcNAc and cluster into distinct macromolecular complexes. 35230102 3 26 theme increasing 329:338 arg1 interest 340:347 the increasing interest 325:347 the increasing interest in this phenomenon 325:366 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 2 27 theme such 216:219 arg1 modifications 221:233 such modifications 216:233 such modifications 216:233 One emerging manner by which such modifications regulate protein functions is through their ability to perturb protein stability. 35230102 1 28 theme proteins 135:142 arg1 properties 121:130 the biophysical properties 105:130 the biophysical properties of proteins 105:142 Posttranslational modifications alter the biophysical properties of proteins and thereby influence cellular physiology. 35230102 3 29 theme posttranslational 454:470 arg1 modifications 472:484 posttranslational modifications 454:484 posttranslational modifications 454:484 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 5 30 from hundreds 807:814 arg1 mammals 831:837 mammals 831:837 mammals that has been shown in select cases to stabilize proteins 831:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 8 31 theme protein 1358:1364 arg1 stability 1366:1374 protein stability 1358:1374 protein stability 1358:1374 These results establish O-GlcNAc as a bidirectional regulator of protein stability and provide a blueprint for exploring the impact of any protein modification on the meltome of, in principle, any organism. 35230102 3 32 theme modifications 472:484 arg1 effects 443:449 the biophysical effects 427:449 the biophysical effects of posttranslational modifications on the proteome 427:500 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 4 33 theme protein 584:590 arg1 modifications 592:604 protein modifications 584:604 protein modifications 584:604 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 35230102 5 34 theme abundant 776:783 arg1 modification 785:796 an abundant modification 773:796 an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins 773:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 5 34 theme abundant 776:783 arg1 N-acetylglucosamine 741:759 O-linked N-acetylglucosamine 732:759 O-linked N-acetylglucosamine (O-GlcNAc) 732:770 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 6 35 theme thermal 909:915 arg1 strategy 937:944 this thermal proteomic profiling strategy 904:944 this thermal proteomic profiling strategy 904:944 Using this thermal proteomic profiling strategy, we identify a set of 72 proteins displaying O-GlcNAc-dependent thermostability and validate this approach using orthogonal methods targeting specific proteins. 35230102 6 36 theme proteins 971:978 arg1 set 961:963 a set 959:963 a set of 72 proteins displaying O-GlcNAc-dependent thermostability 959:1024 Using this thermal proteomic profiling strategy, we identify a set of 72 proteins displaying O-GlcNAc-dependent thermostability and validate this approach using orthogonal methods targeting specific proteins. 35230102 6 36 theme proteins 971:978 arg1 proteins 971:978 72 proteins 968:978 72 proteins displaying O-GlcNAc-dependent thermostability 968:1024 Using this thermal proteomic profiling strategy, we identify a set of 72 proteins displaying O-GlcNAc-dependent thermostability and validate this approach using orthogonal methods targeting specific proteins. 35230102 3 37 theme effects 443:449 arg1 interrogation 410:422 global interrogation 403:422 global interrogation of the biophysical effects of posttranslational modifications on the proteome 403:500 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 6 38 theme O-GlcNAc-dependent 991:1008 arg1 thermostability 1010:1024 O-GlcNAc-dependent thermostability 991:1024 O-GlcNAc-dependent thermostability 991:1024 Using this thermal proteomic profiling strategy, we identify a set of 72 proteins displaying O-GlcNAc-dependent thermostability and validate this approach using orthogonal methods targeting specific proteins. 35230102 5 39 theme O-linked 732:739 arg1 modification 785:796 an abundant modification 773:796 an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins 773:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 5 39 theme O-linked 732:739 arg1 O-GlcNAc 762:769 O-GlcNAc 762:769 O-GlcNAc 762:769 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 5 39 theme O-linked 732:739 arg1 N-acetylglucosamine 741:759 O-linked N-acetylglucosamine 732:759 O-linked N-acetylglucosamine (O-GlcNAc) 732:770 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 5 40 theme proteins 819:826 arg1 hundreds 807:814 hundreds 807:814 hundreds of proteins in mammals that has been shown in select cases to stabilize proteins 807:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 6 41 theme profiling 927:935 arg1 strategy 937:944 this thermal proteomic profiling strategy 904:944 this thermal proteomic profiling strategy 904:944 Using this thermal proteomic profiling strategy, we identify a set of 72 proteins displaying O-GlcNAc-dependent thermostability and validate this approach using orthogonal methods targeting specific proteins. 35230102 5 42 theme N-acetylglucosamine 741:759 arg1 effects 721:727 the effects 717:727 the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins 717:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 5 43 theme profiling 689:697 arg1 strategy 699:706 this profiling strategy 684:706 this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins 684:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 4 44 theme modifications 592:604 arg1 influence 571:579 the influence 567:579 the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel 567:672 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 35230102 7 45 theme collective 1113:1122 arg1 observations 1124:1135 These collective observations 1107:1135 These collective observations 1107:1135 These collective observations reveal that the majority of proteins influenced by O-GlcNAc are, surprisingly, destabilized by O-GlcNAc and cluster into distinct macromolecular complexes. 35230102 2 46 theme protein 244:250 arg1 functions 252:260 protein functions 244:260 protein functions 244:260 One emerging manner by which such modifications regulate protein functions is through their ability to perturb protein stability. 35230102 5 47 link O-linked 732:739 arg1 modification 785:796 an abundant modification 773:796 an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins 773:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 5 47 link O-linked 732:739 arg1 O-GlcNAc 762:769 O-GlcNAc 762:769 O-GlcNAc 762:769 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 5 47 link O-linked 732:739 arg1 N-acetylglucosamine 741:759 O-linked N-acetylglucosamine 732:759 O-linked N-acetylglucosamine (O-GlcNAc) 732:770 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 3 48 from interest 340:347 arg1 phenomenon 357:366 this phenomenon 352:366 this phenomenon 352:366 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 2 49 theme protein 298:304 arg1 stability 306:314 protein stability 298:314 protein stability 298:314 One emerging manner by which such modifications regulate protein functions is through their ability to perturb protein stability. 35230102 5 50 located found 798:802 arg2 modification 785:796 an abundant modification 773:796 an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins 773:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 5 50 located found 798:802 arg1 hundreds 807:814 hundreds 807:814 hundreds of proteins in mammals that has been shown in select cases to stabilize proteins 807:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 5 50 located found 798:802 arg2 N-acetylglucosamine 741:759 O-linked N-acetylglucosamine 732:759 O-linked N-acetylglucosamine (O-GlcNAc) 732:770 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 1 51 theme cellular 166:173 arg1 physiology 175:184 cellular physiology 166:184 cellular physiology 166:184 Posttranslational modifications alter the biophysical properties of proteins and thereby influence cellular physiology. 35230102 8 52 theme bidirectional 1331:1343 arg1 regulator 1345:1353 a bidirectional regulator 1329:1353 a bidirectional regulator of protein stability 1329:1374 These results establish O-GlcNAc as a bidirectional regulator of protein stability and provide a blueprint for exploring the impact of any protein modification on the meltome of, in principle, any organism. 35230102 8 52 theme bidirectional 1331:1343 arg1 O-GlcNAc 1317:1324 O-GlcNAc 1317:1324 O-GlcNAc 1317:1324 These results establish O-GlcNAc as a bidirectional regulator of protein stability and provide a blueprint for exploring the impact of any protein modification on the meltome of, in principle, any organism. 35230102 5 53 from proteins 819:826 arg1 mammals 831:837 mammals 831:837 mammals that has been shown in select cases to stabilize proteins 831:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 5 54 from mammals 831:837 arg1 hundreds 807:814 hundreds 807:814 hundreds of proteins in mammals that has been shown in select cases to stabilize proteins 807:895 We apply this profiling strategy to study the effects of O-linked N-acetylglucosamine (O-GlcNAc), an abundant modification found on hundreds of proteins in mammals that has been shown in select cases to stabilize proteins. 35230102 3 55 theme few 379:381 arg1 methods 383:389 few methods 379:389 few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome 379:500 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 3 56 from effects 443:449 arg1 proteome 493:500 the proteome 489:500 the proteome 489:500 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 6 57 theme specific 1088:1095 arg1 proteins 1097:1104 specific proteins 1088:1104 specific proteins 1088:1104 Using this thermal proteomic profiling strategy, we identify a set of 72 proteins displaying O-GlcNAc-dependent thermostability and validate this approach using orthogonal methods targeting specific proteins. 35230102 3 58 from proteome 493:500 arg1 interrogation 410:422 global interrogation 403:422 global interrogation of the biophysical effects of posttranslational modifications on the proteome 403:500 Despite the increasing interest in this phenomenon, there are few methods that enable global interrogation of the biophysical effects of posttranslational modifications on the proteome. 35230102 7 59 theme macromolecular 1267:1280 arg1 complexes 1282:1290 distinct macromolecular complexes 1258:1290 distinct macromolecular complexes 1258:1290 These collective observations reveal that the majority of proteins influenced by O-GlcNAc are, surprisingly, destabilized by O-GlcNAc and cluster into distinct macromolecular complexes. 35230102 4 60 from proteins 653:660 arg1 parallel 665:672 parallel 665:672 parallel 665:672 Here, we describe an unbiased proteome-wide approach to explore the influence of protein modifications on the thermodynamic stability of thousands of proteins in parallel. 36861209 18 0 dep linearity 2963:2971 arg1 coefficients 2986:2997 correlation coefficients 2974:2997 correlation coefficients (R2)≥ 0.9999 2974:3010 Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. 36861209 18 0 dep linearity 2963:2971 arg1 R2 3000:3001 R2 3000:3001 R2 3000:3001 Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. 36861209 4 1 theme frequent 533:540 arg1 urination 542:550 frequent urination 533:550 frequent urination 533:550 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 7 2 with Lignans 816:822 arg1 skeleton 858:865 a dibenzocyclooctadiene-type skeleton 829:865 a dibenzocyclooctadiene-type skeleton 829:865 Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. 36861209 21 3 dep % 3247:3247 arg1 to 3249:3250 to 3249:3250 to 3249:3250 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 11 4 theme MSPD 1378:1381 arg1 simple 1393:1398 simple 1393:1398 simple 1393:1398 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 11 4 theme MSPD 1378:1381 arg1 method 1383:1388 The MSPD method 1374:1388 The MSPD method 1374:1388 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 24 5 from samples 3684:3690 arg1 lignans 3650:3656 five lignans 3645:3656 five lignans from Schisandra chinensis samples from 17 cultivation areas 3645:3716 Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas. 36861209 9 6 theme pretreatment 1122:1133 arg1 methods 1135:1141 study pretreatment methods 1116:1141 study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine 1116:1228 Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. 36861209 14 7 theme inverse 2271:2277 arg1 adsorbents 2279:2288 the inverse adsorbents 2267:2288 the inverse adsorbents 2267:2288 First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. 36861209 12 8 theme high 1684:1687 arg1 MSPD-HPLC 1724:1732 MSPD-HPLC 1724:1732 MSPD-HPLC 1724:1732 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 8 theme high 1684:1687 arg1 chromatography 1708:1721 high performance liquid chromatography 1684:1721 high performance liquid chromatography (MSPD-HPLC) 1684:1733 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 17 9 theme MSPD 2672:2675 arg1 method 2677:2682 the MSPD method 2668:2682 the MSPD method 2668:2682 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 21 10 theme recovery 3223:3230 arg1 % 3257:3257 92.2% to 111.2% 3243:3257 92.2% to 111.2% 3243:3257 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 21 10 theme recovery 3223:3230 arg1 rates 3232:3236 The average recovery rates 3211:3236 The average recovery rates 3211:3236 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 23 11 theme combined 3477:3484 arg1 extraction 3486:3495 combined extraction 3477:3495 combined extraction 3477:3495 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 15 12 theme lignans 2494:2500 arg1 yields 2484:2489 the extraction yields 2469:2489 the extraction yields of lignans 2469:2500 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 15 13 theme mass 2402:2405 arg1 effects 2387:2393 effects 2387:2393 effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans 2387:2500 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 16 14 theme lignans 2579:2585 arg1 analysis 2567:2574 MSPD-HPLC analysis 2557:2574 MSPD-HPLC analysis of lignans from Schisandra chinensis 2557:2611 Xion was chosen as an adsorbent for MSPD-HPLC analysis of lignans from Schisandra chinensis. 36861209 18 15 dep coefficients 2986:2997 arg1 0.9999 3005:3010 0.9999 3005:3010 0.9999 3005:3010 Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. 36861209 24 16 from areas 3712:3716 arg1 samples 3684:3690 Schisandra chinensis samples 3663:3690 Schisandra chinensis samples from 17 cultivation areas 3663:3716 Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas. 36861209 9 17 theme sample 1155:1160 arg1 preparation 1162:1172 sample preparation 1155:1172 sample preparation 1155:1172 Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. 36861209 2 18 theme popular 306:312 arg1 remedies 314:321 the most popular remedies 297:321 the most popular remedies used in traditional Chinese medicine 297:358 Baill, which belongs to the Schisandraceae family, is among the most popular remedies used in traditional Chinese medicine. 36861209 15 19 theme type 2429:2432 arg1 mass 2402:2405 the mass 2398:2405 the mass of the adsorbent, the type of eluent, and volume of eluent 2398:2464 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 12 20 theme solid-phase 1645:1655 arg1 extraction 1668:1677 matrix solid-phase dispersion extraction 1638:1677 matrix solid-phase dispersion extraction 1638:1677 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 23 21 contain has 3455:3457 arg1 MSPD 3450:3453 MSPD 3450:3453 MSPD 3450:3453 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 23 21 contain has 3455:3457 arg2 advantages 3463:3472 the advantages 3459:3472 the advantages of combined extraction and purification 3459:3512 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 20 22 theme low 3181:3183 arg1 levels 3203:3208 low, medium, and high levels 3181:3208 low, medium, and high levels 3181:3208 Lignans were tested at low, medium, and high levels. 36861209 18 23 theme good 2958:2961 arg1 linearity 2963:2971 good linearity 2958:2971 good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte 2958:3035 Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. 36861209 17 24 theme Schisandra 2724:2733 arg1 powder 2745:2750 Schisandra chinensis powder 2724:2750 Schisandra chinensis powder (0.25 g) 2724:2759 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 17 24 theme Schisandra 2724:2733 arg1 g 2758:2758 0.25 g 2753:2758 0.25 g 2753:2758 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 9 25 theme quality 1182:1188 arg1 control 1190:1196 the quality control 1178:1196 the quality control of traditional Chinese medicine 1178:1228 Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. 36861209 12 26 theme schizandrin 1870:1880 arg1 lignans 1794:1800 five lignans 1789:1800 five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) 1789:1883 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 26 theme schizandrin 1870:1880 arg1 C 1882:1882 schizandrin C 1870:1882 schizandrin C 1870:1882 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 27 from determination 1772:1784 arg1 chinensis 1899:1907 chinensis 1899:1907 chinensis 1899:1907 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 21 28 theme 3.54 3311:3314 arg1 % 3306:3306 % 3306:3306 % 3306:3306 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 5 29 theme bioactive 614:622 arg1 sterols 722:728 sterols 722:728 sterols 722:728 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 29 theme bioactive 614:622 arg1 lignans 646:652 lignans 646:652 lignans 646:652 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 29 theme bioactive 614:622 arg1 acids 694:698 organic acids 686:698 organic acids 686:698 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 29 theme bioactive 614:622 arg1 constituents 624:635 bioactive constituents 614:635 bioactive constituents 614:635 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 29 theme bioactive 614:622 arg1 oils 665:668 essential oils 655:668 essential oils 655:668 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 29 theme bioactive 614:622 arg1 polysaccharides 701:715 polysaccharides 701:715 polysaccharides 701:715 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 29 theme bioactive 614:622 arg1 triterpenoids 671:683 triterpenoids 671:683 triterpenoids 671:683 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 13 30 theme 0.1 1989:1991 arg1 % 1992:1992 % 1992:1992 % 1992:1992 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 13 31 theme % 1992:1992 arg1 acid 2007:2010 0.1% (v/v) formic acid 1989:2010 0.1% (v/v) formic acid aqueous solution 1989:2027 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 13 32 with column 1955:1960 arg1 elution 1978:1984 a gradient elution 1967:1984 a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile 1967:2044 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 17 33 theme chinensis 2735:2743 arg1 powder 2745:2750 Schisandra chinensis powder 2724:2750 Schisandra chinensis powder (0.25 g) 2724:2759 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 17 33 theme chinensis 2735:2743 arg1 g 2758:2758 0.25 g 2753:2758 0.25 g 2753:2758 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 11 34 theme samples 1436:1442 arg1 number 1426:1431 only a small number 1413:1431 only a small number of samples and solvents 1413:1455 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 9 35 theme Chinese 1213:1219 arg1 medicine 1221:1228 traditional Chinese medicine 1201:1228 traditional Chinese medicine 1201:1228 Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. 36861209 14 36 theme silica 2170:2175 arg1 gel 2177:2179 silica gel 2170:2179 silica gel 2170:2179 First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. 36861209 5 37 theme organic 686:692 arg1 acids 694:698 organic acids 686:698 organic acids 686:698 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 7 38 theme main 915:918 arg1 ingredients 930:940 main bioactive ingredients 915:940 main bioactive ingredients 915:940 Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. 36861209 16 39 from chinensis 2603:2611 arg1 lignans 2579:2585 lignans 2579:2585 lignans from Schisandra chinensis 2579:2611 Xion was chosen as an adsorbent for MSPD-HPLC analysis of lignans from Schisandra chinensis. 36861209 16 39 from chinensis 2603:2611 arg1 analysis 2567:2574 MSPD-HPLC analysis 2557:2574 MSPD-HPLC analysis of lignans from Schisandra chinensis 2557:2611 Xion was chosen as an adsorbent for MSPD-HPLC analysis of lignans from Schisandra chinensis. 36861209 18 40 from chinensis 2923:2931 arg1 lignans 2899:2905 five lignans 2894:2905 five lignans from Schisandra chinensis 2894:2931 Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. 36861209 0 41 theme solid-phase 80:90 arg1 chromatography 138:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 14 42 theme alkaline 2215:2222 arg1 alumina 2224:2230 alkaline alumina 2215:2230 alkaline alumina 2215:2230 First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. 36861209 11 43 theme solvents 1448:1455 arg1 number 1426:1431 only a small number 1413:1431 only a small number of samples and solvents 1413:1455 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 0 44 theme extraction-high 103:117 arg1 chromatography 138:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 21 45 dep % 3306:3306 arg1 to 3308:3309 to 3308:3309 to 3308:3309 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 23 46 theme extraction 3430:3439 arg1 methods 3441:3447 ultrasonic extraction methods 3419:3447 ultrasonic extraction methods 3419:3447 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 10 47 theme solid-phase 1238:1248 arg1 process 1298:1304 a comprehensive process 1282:1304 a comprehensive process involving destruction, extraction, fractionation, and purification 1282:1371 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 10 47 theme solid-phase 1238:1248 arg1 MSPD 1273:1276 MSPD 1273:1276 MSPD 1273:1276 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 10 47 theme solid-phase 1238:1248 arg1 extraction 1261:1270 Matrix solid-phase dispersion extraction 1231:1270 Matrix solid-phase dispersion extraction (MSPD) 1231:1277 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 0 48 theme liquid 131:136 arg1 chromatography 138:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 8 49 theme complex 991:997 arg1 composition 999:1009 the complex composition 987:1009 the complex composition of Schisandra chinensis 987:1033 However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. 36861209 4 50 theme ancient 450:456 arg1 times 458:462 ancient times 450:462 ancient times 450:462 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 0 51 theme matrix 73:78 arg1 chromatography 138:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 21 52 theme standard 3277:3284 arg1 deviations 3286:3295 the relative standard deviations 3264:3295 the relative standard deviations 3264:3295 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 21 52 theme standard 3277:3284 arg1 % 3315:3315 0.23% to 3.54% 3302:3315 0.23% to 3.54% 3302:3315 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 3 53 theme vine 412:415 arg1 name 373:376 The English name 361:376 The English name of the plant 361:389 The English name of the plant is "Chinese magnolia vine". 36861209 3 53 theme vine 412:415 arg1 " 416:416 Chinese magnolia vine" 395:416 "Chinese magnolia vine" 394:416 The English name of the plant is "Chinese magnolia vine". 36861209 0 54 theme [Simultaneous 0:12 arg1 determination 14:26 [Simultaneous determination 0:26 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography 0:151 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 12 55 theme schisandrol 1818:1828 arg1 lignans 1794:1800 five lignans 1789:1800 five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) 1789:1883 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 55 theme schisandrol 1818:1828 arg1 B 1830:1830 schisandrol B 1818:1830 schisandrol B 1818:1830 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 14 56 from effects 2134:2140 arg1 extraction 2331:2340 the extraction 2327:2340 the extraction 2327:2340 First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. 36861209 4 57 theme chronic 506:512 arg1 cough 514:518 chronic cough 506:518 chronic cough 506:518 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 23 58 theme reflux 3397:3402 arg1 extraction 3404:3413 hot reflux extraction 3393:3413 hot reflux extraction 3393:3413 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 21 59 theme 111.2 3252:3256 arg1 % 3247:3247 % 3247:3247 % 3247:3247 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 8 60 theme chinensis 1025:1033 arg1 composition 999:1009 the complex composition 987:1009 the complex composition of Schisandra chinensis 987:1033 However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. 36861209 3 61 theme Chinese 395:401 arg1 name 373:376 The English name 361:376 The English name of the plant 361:389 The English name of the plant is "Chinese magnolia vine". 36861209 3 61 theme Chinese 395:401 arg1 " 416:416 Chinese magnolia vine" 395:416 "Chinese magnolia vine" 394:416 The English name of the plant is "Chinese magnolia vine". 36861209 24 62 theme Schisandra 3663:3672 arg1 samples 3684:3690 Schisandra chinensis samples 3663:3690 Schisandra chinensis samples from 17 cultivation areas 3663:3716 Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas. 36861209 17 63 theme high 2690:2693 arg1 value 2772:2776 a fixed value 2764:2776 a fixed value 2764:2776 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 17 63 theme high 2690:2693 arg1 yield 2713:2717 a high lignan extraction yield 2688:2717 a high lignan extraction yield with Schisandra chinensis powder (0.25 g) 2688:2759 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 0 64 theme lignans 36:42 arg1 determination 14:26 [Simultaneous determination 0:26 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography 0:151 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 6 65 theme pharmacological 777:791 arg1 efficacy 793:800 the pharmacological efficacy 773:800 the pharmacological efficacy of the plant 773:813 In some cases, these constituents affects the pharmacological efficacy of the plant. 36861209 11 66 used used 1544:1547 arg2 it 1534:1535 it 1534:1535 it 1534:1535 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 15 67 theme volume 2449:2454 arg1 mass 2402:2405 the mass 2398:2405 the mass of the adsorbent, the type of eluent, and volume of eluent 2398:2464 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 10 68 theme comprehensive 1284:1296 arg1 process 1298:1304 a comprehensive process 1282:1304 a comprehensive process involving destruction, extraction, fractionation, and purification 1282:1371 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 10 68 theme comprehensive 1284:1296 arg1 extraction 1261:1270 Matrix solid-phase dispersion extraction 1231:1270 Matrix solid-phase dispersion extraction (MSPD) 1231:1277 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 2 69 theme Chinese 343:349 arg1 medicine 351:358 traditional Chinese medicine 331:358 traditional Chinese medicine 331:358 Baill, which belongs to the Schisandraceae family, is among the most popular remedies used in traditional Chinese medicine. 36861209 15 70 theme eluent 2459:2464 arg1 type 2429:2432 the type 2425:2432 the type of eluent 2425:2442 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 15 70 theme eluent 2459:2464 arg1 volume 2449:2454 volume 2449:2454 volume 2449:2454 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 21 71 theme 0.23 3302:3305 arg1 % 3306:3306 % 3306:3306 % 3306:3306 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 15 72 dep type 2429:2432 arg1 the 2410:2412 the 2410:2412 the 2410:2412 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 23 73 theme lower 3556:3560 arg1 volumes 3570:3576 lower solvent volumes 3556:3576 lower solvent volumes 3556:3576 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 8 74 theme lignans 1061:1067 arg1 low 1073:1075 low 1073:1075 low 1073:1075 However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. 36861209 8 74 theme lignans 1061:1067 arg1 yields 1051:1056 the extraction yields 1036:1056 the extraction yields of lignans 1036:1067 However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. 36861209 17 75 contain had 2684:2686 arg2 value 2772:2776 a fixed value 2764:2776 a fixed value 2764:2776 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 17 75 contain had 2684:2686 arg1 method 2677:2682 the MSPD method 2668:2682 the MSPD method 2668:2682 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 17 75 contain had 2684:2686 arg2 yield 2713:2717 a high lignan extraction yield 2688:2717 a high lignan extraction yield with Schisandra chinensis powder (0.25 g) 2688:2759 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 1 76 dep chinensis 218:226 arg1 Schisandra 207:216 Schisandra 207:216 Schisandra 207:216 The kidney-shaped, red-colord fruit from the plant, Schisandra chinensis (Turcz.) 36861209 15 77 theme eluent 2437:2442 arg1 type 2429:2432 the type 2425:2432 the type of eluent 2425:2442 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 15 77 theme eluent 2437:2442 arg1 volume 2449:2454 volume 2449:2454 volume 2449:2454 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 13 78 theme target 1914:1919 arg1 phases 2060:2065 the mobile phases 2049:2065 the mobile phases 2049:2065 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 13 78 theme target 1914:1919 arg1 compounds 1921:1929 The target compounds 1910:1929 The target compounds 1910:1929 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 17 79 theme parameters 2645:2654 arg1 Optimization 2614:2625 Optimization 2614:2625 Optimization of the extraction parameters 2614:2654 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 11 80 theme liquid 1560:1565 arg1 samples 1595:1601 liquid, viscous, semi-solid, solid samples 1560:1601 liquid, viscous, semi-solid, solid samples 1560:1601 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 5 81 theme wide 600:603 arg1 sterols 722:728 sterols 722:728 sterols 722:728 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 81 theme wide 600:603 arg1 lignans 646:652 lignans 646:652 lignans 646:652 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 81 theme wide 600:603 arg1 acids 694:698 organic acids 686:698 organic acids 686:698 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 81 theme wide 600:603 arg1 oils 665:668 essential oils 655:668 essential oils 655:668 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 81 theme wide 600:603 arg1 polysaccharides 701:715 polysaccharides 701:715 polysaccharides 701:715 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 81 theme wide 600:603 arg1 triterpenoids 671:683 triterpenoids 671:683 triterpenoids 671:683 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 81 theme wide 600:603 arg1 range 605:609 the wide range 596:609 the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols 596:728 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 9 82 theme study 1116:1120 arg1 methods 1135:1141 study pretreatment methods 1116:1141 study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine 1116:1228 Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. 36861209 7 83 theme bioactive 920:928 arg1 ingredients 930:940 main bioactive ingredients 915:940 main bioactive ingredients 915:940 Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. 36861209 13 84 theme acetonitrile 2033:2044 arg1 elution 1978:1984 a gradient elution 1967:1984 a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile 1967:2044 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 12 85 theme performance 1689:1699 arg1 MSPD-HPLC 1724:1732 MSPD-HPLC 1724:1732 MSPD-HPLC 1724:1732 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 85 theme performance 1689:1699 arg1 chromatography 1708:1721 high performance liquid chromatography 1684:1721 high performance liquid chromatography (MSPD-HPLC) 1684:1733 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 22 86 dep intra-day 3323:3331 arg1 precisions 3347:3356 precisions 3347:3356 precisions 3347:3356 Both intra-day and inter-day precisions were less than 3.6%. 36861209 13 87 dep % 1992:1992 arg1 v/v 1995:1997 v/v 1995:1997 v/v 1995:1997 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 12 88 dep lignans 1794:1800 arg1 deoxyschizandrin 1833:1848 deoxyschizandrin 1833:1848 deoxyschizandrin 1833:1848 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 88 dep lignans 1794:1800 arg1 C 1882:1882 schizandrin C 1870:1882 schizandrin C 1870:1882 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 88 dep lignans 1794:1800 arg1 A 1815:1815 schisandrol A 1803:1815 schisandrol A 1803:1815 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 88 dep lignans 1794:1800 arg1 B 1863:1863 schizandrin B 1851:1863 schizandrin B 1851:1863 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 88 dep lignans 1794:1800 arg1 B 1830:1830 schisandrol B 1818:1830 schisandrol B 1818:1830 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 88 dep lignans 1794:1800 arg1 lignans 1794:1800 five lignans 1789:1800 five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) 1789:1883 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 23 89 theme purification 3501:3512 arg1 advantages 3463:3472 the advantages 3459:3472 the advantages of combined extraction and purification 3459:3512 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 15 90 theme adsorbent 2414:2422 arg1 type 2429:2432 the type 2425:2432 the type of eluent 2425:2442 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 6 91 theme plant 809:813 arg1 efficacy 793:800 the pharmacological efficacy 773:800 the pharmacological efficacy of the plant 773:813 In some cases, these constituents affects the pharmacological efficacy of the plant. 36861209 18 92 theme target 3022:3027 arg1 analyte 3029:3035 each target analyte 3017:3035 each target analyte 3017:3035 Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. 36861209 12 93 theme matrix 1638:1643 arg1 extraction 1668:1677 matrix solid-phase dispersion extraction 1638:1677 matrix solid-phase dispersion extraction 1638:1677 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 16 94 theme MSPD-HPLC 2557:2565 arg1 analysis 2567:2574 MSPD-HPLC analysis 2557:2574 MSPD-HPLC analysis of lignans from Schisandra chinensis 2557:2611 Xion was chosen as an adsorbent for MSPD-HPLC analysis of lignans from Schisandra chinensis. 36861209 14 95 theme neutral 2198:2204 arg1 alumina 2206:2212 neutral alumina 2198:2212 neutral alumina 2198:2212 First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. 36861209 17 96 theme fixed 2766:2770 arg1 value 2772:2776 a fixed value 2764:2776 a fixed value 2764:2776 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 17 96 theme fixed 2766:2770 arg1 yield 2713:2717 a high lignan extraction yield 2688:2717 a high lignan extraction yield with Schisandra chinensis powder (0.25 g) 2688:2759 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 12 97 theme dispersion 1657:1666 arg1 extraction 1668:1677 matrix solid-phase dispersion extraction 1638:1677 matrix solid-phase dispersion extraction 1638:1677 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 19 98 theme quantification 3066:3079 arg1 limits 3042:3047 The limits 3038:3047 The limits of detection and quantification 3038:3079 The limits of detection and quantification ranged from 0.0089 to 0.0294 μg/mL and 0.0267 to 0.0882 μg/mL, respectively. 36861209 11 99 theme special 1482:1488 arg1 equipments 1503:1512 any special experimental equipments 1478:1512 any special experimental equipments 1478:1512 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 11 100 theme experimental 1490:1501 arg1 equipments 1503:1512 any special experimental equipments 1478:1512 any special experimental equipments 1478:1512 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 20 101 theme high 3198:3201 arg1 levels 3203:3208 low, medium, and high levels 3181:3208 low, medium, and high levels 3181:3208 Lignans were tested at low, medium, and high levels. 36861209 24 102 theme cultivation 3700:3710 arg1 areas 3712:3716 17 cultivation areas 3697:3716 17 cultivation areas 3697:3716 Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas. 36861209 21 103 theme 92.2 3243:3246 arg1 % 3247:3247 % 3247:3247 % 3247:3247 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 2 104 theme traditional 331:341 arg1 medicine 351:358 traditional Chinese medicine 331:358 traditional Chinese medicine 331:358 Baill, which belongs to the Schisandraceae family, is among the most popular remedies used in traditional Chinese medicine. 36861209 13 105 theme formic 2000:2005 arg1 acid 2007:2010 0.1% (v/v) formic acid 1989:2010 0.1% (v/v) formic acid aqueous solution 1989:2027 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 17 106 theme extraction 2702:2711 arg1 value 2772:2776 a fixed value 2764:2776 a fixed value 2764:2776 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 17 106 theme extraction 2702:2711 arg1 yield 2713:2717 a high lignan extraction yield 2688:2717 a high lignan extraction yield with Schisandra chinensis powder (0.25 g) 2688:2759 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 16 107 from analysis 2567:2574 arg1 chinensis 2603:2611 chinensis 2603:2611 chinensis 2603:2611 Xion was chosen as an adsorbent for MSPD-HPLC analysis of lignans from Schisandra chinensis. 36861209 5 108 theme essential 655:663 arg1 oils 665:668 essential oils 655:668 essential oils 655:668 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 13 109 theme aqueous 2012:2018 arg1 solution 2020:2027 aqueous solution 2012:2027 0.1% (v/v) formic acid aqueous solution 1989:2027 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 19 110 dep 0.0882 3130:3135 arg1 to 3127:3128 to 3127:3128 to 3127:3128 The limits of detection and quantification ranged from 0.0089 to 0.0294 μg/mL and 0.0267 to 0.0882 μg/mL, respectively. 36861209 14 111 theme acidic 2182:2187 arg1 alumina 2189:2195 acidic alumina 2182:2195 acidic alumina 2182:2195 First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. 36861209 5 112 theme constituents 624:635 arg1 sterols 722:728 sterols 722:728 sterols 722:728 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 112 theme constituents 624:635 arg1 lignans 646:652 lignans 646:652 lignans 646:652 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 112 theme constituents 624:635 arg1 acids 694:698 organic acids 686:698 organic acids 686:698 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 112 theme constituents 624:635 arg1 oils 665:668 essential oils 655:668 essential oils 655:668 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 112 theme constituents 624:635 arg1 polysaccharides 701:715 polysaccharides 701:715 polysaccharides 701:715 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 112 theme constituents 624:635 arg1 triterpenoids 671:683 triterpenoids 671:683 triterpenoids 671:683 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 5 112 theme constituents 624:635 arg1 range 605:609 the wide range 596:609 the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols 596:728 This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. 36861209 9 113 theme traditional 1201:1211 arg1 medicine 1221:1228 traditional Chinese medicine 1201:1228 traditional Chinese medicine 1201:1228 Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. 36861209 2 114 theme Schisandraceae 265:278 arg1 family 280:285 the Schisandraceae family 261:285 the Schisandraceae family 261:285 Baill, which belongs to the Schisandraceae family, is among the most popular remedies used in traditional Chinese medicine. 36861209 7 115 theme chinensis 956:964 arg1 ingredients 930:940 main bioactive ingredients 915:940 main bioactive ingredients 915:940 Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. 36861209 7 115 theme chinensis 956:964 arg1 Lignans 816:822 Lignans 816:822 Lignans with a dibenzocyclooctadiene-type skeleton 816:865 Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. 36861209 7 115 theme chinensis 956:964 arg1 constituents 898:909 the major constituents 888:909 the major constituents 888:909 Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. 36861209 18 116 theme correlation 2974:2984 arg1 coefficients 2986:2997 correlation coefficients 2974:2997 correlation coefficients (R2)≥ 0.9999 2974:3010 Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. 36861209 18 116 theme correlation 2974:2984 arg1 R2 3000:3001 R2 3000:3001 R2 3000:3001 Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. 36861209 11 117 theme small 1420:1424 arg1 number 1426:1431 only a small number 1413:1431 only a small number of samples and solvents 1413:1455 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 4 118 used used 431:434 arg2 It 419:420 It 419:420 It 419:420 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 9 119 theme medicine 1221:1228 arg1 control 1190:1196 the quality control 1178:1196 the quality control of traditional Chinese medicine 1178:1228 Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. 36861209 0 120 theme dispersion 92:101 arg1 chromatography 138:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 13 121 theme gradient 1969:1976 arg1 elution 1978:1984 a gradient elution 1967:1984 a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile 1967:2044 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 1 122 from plant 200:204 arg1 fruit 185:189 fruit 185:189 fruit 185:189 The kidney-shaped, red-colord fruit from the plant, Schisandra chinensis (Turcz.) 36861209 0 123 from determination 14:26 arg1 chinensis 60:68 chinensis 60:68 chinensis 60:68 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 21 124 theme average 3215:3221 arg1 % 3257:3257 92.2% to 111.2% 3243:3257 92.2% to 111.2% 3243:3257 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 21 124 theme average 3215:3221 arg1 rates 3232:3236 The average recovery rates 3211:3236 The average recovery rates 3211:3236 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 14 125 theme adsorbents 2148:2157 arg1 effects 2134:2140 the effects 2130:2140 the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction 2130:2340 First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. 36861209 0 126 theme performance 119:129 arg1 chromatography 138:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 matrix solid-phase dispersion extraction-high performance liquid chromatography 73:151 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 12 127 theme schizandrin 1851:1861 arg1 lignans 1794:1800 five lignans 1789:1800 five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) 1789:1883 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 127 theme schizandrin 1851:1861 arg1 B 1863:1863 schizandrin B 1851:1863 schizandrin B 1851:1863 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 3 128 theme English 365:371 arg1 name 373:376 The English name 361:376 The English name of the plant 361:389 The English name of the plant is "Chinese magnolia vine". 36861209 3 128 theme English 365:371 arg1 " 416:416 Chinese magnolia vine" 395:416 "Chinese magnolia vine" 394:416 The English name of the plant is "Chinese magnolia vine". 36861209 0 129 from chinensis 60:68 arg1 determination 14:26 [Simultaneous determination 0:26 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography 0:151 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 0 129 from chinensis 60:68 arg1 lignans 36:42 five lignans 31:42 five lignans from Schisandra chinensis 31:68 [Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography]. 36861209 1 130 dep kidney-shaped 159:171 arg1 fruit 185:189 fruit 185:189 fruit 185:189 The kidney-shaped, red-colord fruit from the plant, Schisandra chinensis (Turcz.) 36861209 10 131 theme dispersion 1250:1259 arg1 process 1298:1304 a comprehensive process 1282:1304 a comprehensive process involving destruction, extraction, fractionation, and purification 1282:1371 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 10 131 theme dispersion 1250:1259 arg1 MSPD 1273:1276 MSPD 1273:1276 MSPD 1273:1276 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 10 131 theme dispersion 1250:1259 arg1 extraction 1261:1270 Matrix solid-phase dispersion extraction 1231:1270 Matrix solid-phase dispersion extraction (MSPD) 1231:1277 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 13 132 theme C18 1951:1953 arg1 column 1955:1960 a C18 column 1949:1960 a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile 1949:2044 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 8 133 theme composition 999:1009 arg1 low 1073:1075 low 1073:1075 low 1073:1075 However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. 36861209 8 133 theme composition 999:1009 arg1 yields 1051:1056 the extraction yields 1036:1056 the extraction yields of lignans 1036:1067 However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. 36861209 7 134 theme major 892:896 arg1 Lignans 816:822 Lignans 816:822 Lignans with a dibenzocyclooctadiene-type skeleton 816:865 Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. 36861209 7 134 theme major 892:896 arg1 constituents 898:909 the major constituents 888:909 the major constituents 888:909 Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. 36861209 17 135 with yield 2713:2717 arg1 powder 2745:2750 Schisandra chinensis powder 2724:2750 Schisandra chinensis powder (0.25 g) 2724:2759 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 17 135 with yield 2713:2717 arg1 g 2758:2758 0.25 g 2753:2758 0.25 g 2753:2758 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 10 136 theme Matrix 1231:1236 arg1 process 1298:1304 a comprehensive process 1282:1304 a comprehensive process involving destruction, extraction, fractionation, and purification 1282:1371 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 10 136 theme Matrix 1231:1236 arg1 MSPD 1273:1276 MSPD 1273:1276 MSPD 1273:1276 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 10 136 theme Matrix 1231:1236 arg1 extraction 1261:1270 Matrix solid-phase dispersion extraction 1231:1270 Matrix solid-phase dispersion extraction (MSPD) 1231:1277 Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. 36861209 3 137 theme plant 385:389 arg1 name 373:376 The English name 361:376 The English name of the plant 361:389 The English name of the plant is "Chinese magnolia vine". 36861209 3 137 theme plant 385:389 arg1 " 416:416 Chinese magnolia vine" 395:416 "Chinese magnolia vine" 394:416 The English name of the plant is "Chinese magnolia vine". 36861209 23 138 theme ultrasonic 3419:3428 arg1 methods 3441:3447 ultrasonic extraction methods 3419:3447 ultrasonic extraction methods 3419:3447 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 15 139 theme extraction 2473:2482 arg1 yields 2484:2489 the extraction yields 2469:2489 the extraction yields of lignans 2469:2500 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 11 140 dep liquid 1560:1565 arg1 semi-solid 1577:1586 semi-solid 1577:1586 semi-solid 1577:1586 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 11 140 dep liquid 1560:1565 arg1 viscous 1568:1574 viscous 1568:1574 viscous 1568:1574 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 11 140 dep liquid 1560:1565 arg1 solid 1589:1593 solid 1589:1593 solid 1589:1593 The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. 36861209 12 141 theme lignans 1794:1800 arg1 determination 1772:1784 the simultaneous determination 1755:1784 the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis 1755:1907 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 13 142 dep nm 2119:2120 arg1 a 2099:2099 a 2099:2099 a 2099:2099 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 13 142 dep nm 2119:2120 arg1 wavelength 2101:2110 wavelength 2101:2110 wavelength 2101:2110 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 24 143 theme chinensis 3674:3682 arg1 samples 3684:3690 Schisandra chinensis samples 3663:3690 Schisandra chinensis samples from 17 cultivation areas 3663:3716 Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas. 36861209 19 144 dep 0.0294 3103:3108 arg1 to 3100:3101 to 3100:3101 to 3100:3101 The limits of detection and quantification ranged from 0.0089 to 0.0294 μg/mL and 0.0267 to 0.0882 μg/mL, respectively. 36861209 12 145 theme schisandrol 1803:1813 arg1 lignans 1794:1800 five lignans 1789:1800 five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) 1789:1883 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 145 theme schisandrol 1803:1813 arg1 A 1815:1815 schisandrol A 1803:1815 schisandrol A 1803:1815 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 18 146 theme Analytical 2856:2865 arg1 methods 2867:2873 Analytical methods 2856:2873 Analytical methods 2856:2873 Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. 36861209 3 147 theme magnolia 403:410 arg1 name 373:376 The English name 361:376 The English name of the plant 361:389 The English name of the plant is "Chinese magnolia vine". 36861209 3 147 theme magnolia 403:410 arg1 " 416:416 Chinese magnolia vine" 395:416 "Chinese magnolia vine" 394:416 The English name of the plant is "Chinese magnolia vine". 36861209 4 148 theme ailments 486:493 arg1 urination 542:550 frequent urination 533:550 frequent urination 533:550 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 4 148 theme ailments 486:493 arg1 variety 475:481 a variety 473:481 a variety 473:481 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 4 148 theme ailments 486:493 arg1 cough 514:518 chronic cough 506:518 chronic cough 506:518 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 4 148 theme ailments 486:493 arg1 diarrhea 553:560 diarrhea 553:560 diarrhea 553:560 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 4 148 theme ailments 486:493 arg1 dyspnea 524:530 dyspnea 524:530 dyspnea 524:530 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 4 148 theme ailments 486:493 arg1 ailments 486:493 ailments 486:493 ailments 486:493 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 4 148 theme ailments 486:493 arg1 diabetes 567:574 diabetes 567:574 diabetes 567:574 It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. 36861209 23 149 theme hot 3393:3395 arg1 extraction 3404:3413 hot reflux extraction 3393:3413 hot reflux extraction 3393:3413 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 15 150 from effects 2387:2393 arg1 yields 2484:2489 the extraction yields 2469:2489 the extraction yields of lignans 2469:2500 Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. 36861209 23 151 theme solvent 3562:3568 arg1 volumes 3570:3576 lower solvent volumes 3556:3576 lower solvent volumes 3556:3576 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 17 152 theme lignan 2695:2700 arg1 value 2772:2776 a fixed value 2764:2776 a fixed value 2764:2776 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 17 152 theme lignan 2695:2700 arg1 yield 2713:2717 a high lignan extraction yield 2688:2717 a high lignan extraction yield with Schisandra chinensis powder (0.25 g) 2688:2759 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 23 153 theme extraction 3486:3495 arg1 advantages 3463:3472 the advantages 3459:3472 the advantages of combined extraction and purification 3459:3512 Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. 36861209 12 154 theme simultaneous 1759:1770 arg1 determination 1772:1784 the simultaneous determination 1755:1784 the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis 1755:1907 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 17 155 theme elution 2831:2837 arg1 solvent 2839:2845 the elution solvent 2827:2845 the elution solvent (15 mL) 2827:2853 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 17 155 theme elution 2831:2837 arg1 mL 2851:2852 15 mL 2848:2852 15 mL 2848:2852 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36861209 13 156 theme acid 2007:2010 arg1 elution 1978:1984 a gradient elution 1967:1984 a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile 1967:2044 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 7 157 theme dibenzocyclooctadiene-type 831:856 arg1 skeleton 858:865 a dibenzocyclooctadiene-type skeleton 829:865 a dibenzocyclooctadiene-type skeleton 829:865 Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. 36861209 8 158 theme extraction 1040:1049 arg1 low 1073:1075 low 1073:1075 low 1073:1075 However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. 36861209 8 158 theme extraction 1040:1049 arg1 yields 1051:1056 the extraction yields 1036:1056 the extraction yields of lignans 1036:1067 However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. 36861209 13 159 dep acid 2007:2010 arg1 solution 2020:2027 aqueous solution 2012:2027 0.1% (v/v) formic acid aqueous solution 1989:2027 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 19 160 theme detection 3052:3060 arg1 limits 3042:3047 The limits 3038:3047 The limits of detection and quantification 3038:3079 The limits of detection and quantification ranged from 0.0089 to 0.0294 μg/mL and 0.0267 to 0.0882 μg/mL, respectively. 36861209 13 161 theme mobile 2053:2058 arg1 phases 2060:2065 the mobile phases 2049:2065 the mobile phases 2049:2065 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 13 161 theme mobile 2053:2058 arg1 compounds 1921:1929 The target compounds 1910:1929 The target compounds 1910:1929 The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. 36861209 21 162 theme relative 3268:3275 arg1 deviations 3286:3295 the relative standard deviations 3264:3295 the relative standard deviations 3264:3295 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 21 162 theme relative 3268:3275 arg1 % 3315:3315 0.23% to 3.54% 3302:3315 0.23% to 3.54% 3302:3315 The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. 36861209 12 163 theme liquid 1701:1706 arg1 MSPD-HPLC 1724:1732 MSPD-HPLC 1724:1732 MSPD-HPLC 1724:1732 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 12 163 theme liquid 1701:1706 arg1 chromatography 1708:1721 high performance liquid chromatography 1684:1721 high performance liquid chromatography (MSPD-HPLC) 1684:1733 In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. 36861209 24 164 theme optimized 3592:3600 arg1 method 3602:3607 the optimized method 3588:3607 the optimized method 3588:3607 Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas. 36861209 20 165 theme medium 3186:3191 arg1 levels 3203:3208 low, medium, and high levels 3181:3208 low, medium, and high levels 3181:3208 Lignans were tested at low, medium, and high levels. 36861209 17 166 theme extraction 2634:2643 arg1 parameters 2645:2654 the extraction parameters 2630:2654 the extraction parameters 2630:2654 Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). 36716818 4 0 theme signaling 487:495 arg1 mechanism 497:505 signaling mechanism 487:505 signaling mechanism 487:505 However, the structural organization and signaling mechanism for these tandem domains remain unclear. 36716818 5 1 theme HormR 626:630 arg1 domains 642:648 the SEA, HormR, and GAIN domains 617:648 the SEA, HormR, and GAIN domains 617:648 Here, we report the crystal structure of a GPR110 fragment composing the SEA, HormR, and GAIN domains at 2.9 Å resolution. 36716818 1 2 theme immune 133:138 arg1 responses 140:148 human immune responses 127:148 human immune responses 127:148 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 8 3 theme fragment 1095:1102 arg1 expression 1056:1065 expression 1056:1065 expression of the GPR110 extracellular fragment 1056:1102 These interactions appear to be critical for folding, as removal of the glycosylation site greatly decreases expression of the GPR110 extracellular fragment. 36716818 10 4 theme receptor 1375:1382 arg1 activation 1384:1393 receptor activation 1375:1393 receptor activation 1375:1393 This suggests that the agonist may function by removing the Stachel peptide which in turn redocks to the orthosteric pocket for receptor activation. 36716818 5 5 theme GAIN 637:640 arg1 domains 642:648 the SEA, HormR, and GAIN domains 617:648 the SEA, HormR, and GAIN domains 617:648 Here, we report the crystal structure of a GPR110 fragment composing the SEA, HormR, and GAIN domains at 2.9 Å resolution. 36716818 10 6 theme orthosteric 1352:1362 arg1 pocket 1364:1369 the orthosteric pocket 1348:1369 the orthosteric pocket for receptor activation 1348:1393 This suggests that the agonist may function by removing the Stachel peptide which in turn redocks to the orthosteric pocket for receptor activation. 36716818 6 7 theme complementary 784:796 arg1 interfaces 798:807 complementary interfaces 784:807 complementary interfaces 784:807 The structure together with MD simulations reveal rigid connections between these domains that are stabilized by complementary interfaces. 36716818 4 8 theme structural 459:468 arg1 organization 470:481 structural organization 459:481 structural organization 459:481 However, the structural organization and signaling mechanism for these tandem domains remain unclear. 36716818 1 9 theme Adhesion 58:65 arg1 aGPCRs 96:101 aGPCRs 96:101 aGPCRs 96:101 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 1 9 theme Adhesion 58:65 arg1 receptors 85:93 Adhesion G protein-coupled receptors 58:93 Adhesion G protein-coupled receptors (aGPCRs) 58:102 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 5 10 theme GPR110 591:596 arg1 fragment 598:605 a GPR110 fragment 589:605 a GPR110 fragment composing the SEA, HormR, and GAIN domains at 2.9 Å resolution 589:668 Here, we report the crystal structure of a GPR110 fragment composing the SEA, HormR, and GAIN domains at 2.9 Å resolution. 36716818 0 11 theme Crystal 0:6 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of the extracellular domains of GPR110 0:55 Crystal structure of the extracellular domains of GPR110. 36716818 11 12 theme structural 1416:1425 arg1 findings 1427:1434 our structural findings 1412:1434 our structural findings 1412:1434 Taken together, our structural findings and analyses provide novel insights into the activation mechanism for aGPCRs. 36716818 7 13 link N-linked 831:838 arg1 carbohydrates 840:852 N-linked carbohydrates 831:852 N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain 831:944 Strikingly, we found N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain. 36716818 8 14 theme site 1033:1036 arg1 removal 1004:1010 removal 1004:1010 removal of the glycosylation site 1004:1036 These interactions appear to be critical for folding, as removal of the glycosylation site greatly decreases expression of the GPR110 extracellular fragment. 36716818 5 15 theme fragment 598:605 arg1 structure 576:584 the crystal structure 564:584 the crystal structure of a GPR110 fragment composing the SEA, HormR, and GAIN domains at 2.9 Å resolution 564:668 Here, we report the crystal structure of a GPR110 fragment composing the SEA, HormR, and GAIN domains at 2.9 Å resolution. 36716818 1 16 theme G 67:67 arg1 aGPCRs 96:101 aGPCRs 96:101 aGPCRs 96:101 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 1 16 theme G 67:67 arg1 receptors 85:93 Adhesion G protein-coupled receptors 58:93 Adhesion G protein-coupled receptors (aGPCRs) 58:102 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 8 17 theme glycosylation 1019:1031 arg1 site 1033:1036 the glycosylation site 1015:1036 the glycosylation site 1015:1036 These interactions appear to be critical for folding, as removal of the glycosylation site greatly decreases expression of the GPR110 extracellular fragment. 36716818 3 18 contain contains 346:353 arg1 region 400:405 the extracellular region 382:405 the extracellular region that mediate inter-cellular signaling 382:443 GPR110 contains tandem adhesion domains at the extracellular region that mediate inter-cellular signaling. 36716818 3 18 contain contains 346:353 arg1 GPR110 339:344 GPR110 339:344 GPR110 339:344 GPR110 contains tandem adhesion domains at the extracellular region that mediate inter-cellular signaling. 36716818 3 18 contain contains 346:353 arg2 domains 371:377 tandem adhesion domains 355:377 tandem adhesion domains 355:377 GPR110 contains tandem adhesion domains at the extracellular region that mediate inter-cellular signaling. 36716818 3 18 contain contains 346:353 arg2 GPR110 339:344 GPR110 339:344 GPR110 339:344 GPR110 contains tandem adhesion domains at the extracellular region that mediate inter-cellular signaling. 36716818 1 19 theme protein-coupled 69:83 arg1 aGPCRs 96:101 aGPCRs 96:101 aGPCRs 96:101 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 1 19 theme protein-coupled 69:83 arg1 receptors 85:93 Adhesion G protein-coupled receptors 58:93 Adhesion G protein-coupled receptors (aGPCRs) 58:102 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 1 20 theme cellular 151:158 arg1 communication 160:172 cellular communication 151:172 cellular communication 151:172 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 3 21 theme tandem 355:360 arg1 domains 371:377 tandem adhesion domains 355:377 tandem adhesion domains 355:377 GPR110 contains tandem adhesion domains at the extracellular region that mediate inter-cellular signaling. 36716818 5 22 theme SEA 621:623 arg1 domains 642:648 the SEA, HormR, and GAIN domains 617:648 the SEA, HormR, and GAIN domains 617:648 Here, we report the crystal structure of a GPR110 fragment composing the SEA, HormR, and GAIN domains at 2.9 Å resolution. 36716818 7 23 theme preceding 923:931 arg1 domain 939:944 the preceding HormR domain 919:944 the preceding HormR domain 919:944 Strikingly, we found N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain. 36716818 7 24 theme N-linked 831:838 arg1 carbohydrates 840:852 N-linked carbohydrates 831:852 N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain 831:944 Strikingly, we found N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain. 36716818 3 25 theme adhesion 362:369 arg1 domains 371:377 tandem adhesion domains 355:377 tandem adhesion domains 355:377 GPR110 contains tandem adhesion domains at the extracellular region that mediate inter-cellular signaling. 36716818 7 26 with contacts 905:912 arg1 domain 939:944 the preceding HormR domain 919:944 the preceding HormR domain 919:944 Strikingly, we found N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain. 36716818 5 27 theme crystal 568:574 arg1 structure 576:584 the crystal structure 564:584 the crystal structure of a GPR110 fragment composing the SEA, HormR, and GAIN domains at 2.9 Å resolution 564:668 Here, we report the crystal structure of a GPR110 fragment composing the SEA, HormR, and GAIN domains at 2.9 Å resolution. 36716818 4 28 dep organization 470:481 arg1 the 455:457 the 455:457 the 455:457 However, the structural organization and signaling mechanism for these tandem domains remain unclear. 36716818 9 29 theme Stachel 1212:1218 arg1 peptide 1220:1226 the Stachel peptide 1208:1226 the Stachel peptide 1208:1226 We further demonstrate that the ligand synaptamide fits well within the hydrophobic pocket occupied by the Stachel peptide in the rest state. 36716818 11 30 theme novel 1457:1461 arg1 insights 1463:1470 novel insights 1457:1470 novel insights into the activation mechanism for aGPCRs 1457:1511 Taken together, our structural findings and analyses provide novel insights into the activation mechanism for aGPCRs. 36716818 1 31 theme organ 175:179 arg1 development 181:191 organ development 175:191 organ development 175:191 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 11 32 theme activation 1481:1490 arg1 mechanism 1492:1500 the activation mechanism 1477:1500 the activation mechanism for aGPCRs 1477:1511 Taken together, our structural findings and analyses provide novel insights into the activation mechanism for aGPCRs. 36716818 9 33 theme hydrophobic 1177:1187 arg1 pocket 1189:1194 the hydrophobic pocket 1173:1194 the hydrophobic pocket occupied by the Stachel peptide in the rest state 1173:1244 We further demonstrate that the ligand synaptamide fits well within the hydrophobic pocket occupied by the Stachel peptide in the rest state. 36716818 0 34 theme domains 39:45 arg1 structure 8:16 Crystal structure 0:16 Crystal structure of the extracellular domains of GPR110 0:55 Crystal structure of the extracellular domains of GPR110. 36716818 8 35 theme GPR110 1074:1079 arg1 fragment 1095:1102 the GPR110 extracellular fragment 1070:1102 the GPR110 extracellular fragment 1070:1102 These interactions appear to be critical for folding, as removal of the glycosylation site greatly decreases expression of the GPR110 extracellular fragment. 36716818 7 36 theme domain 883:888 arg1 N389 866:869 N389 866:869 N389 of the GAIN domain form extensive contacts with the preceding HormR domain 866:944 Strikingly, we found N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain. 36716818 0 37 theme extracellular 25:37 arg1 domains 39:45 the extracellular domains 21:45 the extracellular domains of GPR110 21:55 Crystal structure of the extracellular domains of GPR110. 36716818 0 37 theme extracellular 25:37 arg1 GPR110 50:55 GPR110 50:55 GPR110 50:55 Crystal structure of the extracellular domains of GPR110. 36716818 3 38 theme extracellular 386:398 arg1 region 400:405 the extracellular region 382:405 the extracellular region that mediate inter-cellular signaling 382:443 GPR110 contains tandem adhesion domains at the extracellular region that mediate inter-cellular signaling. 36716818 0 39 theme GPR110 50:55 arg1 domains 39:45 the extracellular domains 21:45 the extracellular domains of GPR110 21:55 Crystal structure of the extracellular domains of GPR110. 36716818 0 39 theme GPR110 50:55 arg1 GPR110 50:55 GPR110 50:55 GPR110 50:55 Crystal structure of the extracellular domains of GPR110. 36716818 4 40 theme tandem 517:522 arg1 domains 524:530 these tandem domains 511:530 these tandem domains 511:530 However, the structural organization and signaling mechanism for these tandem domains remain unclear. 36716818 7 41 attach attached 854:861 arg2 carbohydrates 840:852 N-linked carbohydrates 831:852 N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain 831:944 Strikingly, we found N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain. 36716818 7 41 attach attached 854:861 arg1 N389 866:869 N389 866:869 N389 of the GAIN domain form extensive contacts with the preceding HormR domain 866:944 Strikingly, we found N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain. 36716818 9 42 theme rest 1235:1238 arg1 state 1240:1244 the rest state 1231:1244 the rest state 1231:1244 We further demonstrate that the ligand synaptamide fits well within the hydrophobic pocket occupied by the Stachel peptide in the rest state. 36716818 7 43 theme HormR 933:937 arg1 domain 939:944 the preceding HormR domain 919:944 the preceding HormR domain 919:944 Strikingly, we found N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain. 36716818 8 44 theme extracellular 1081:1093 arg1 fragment 1095:1102 the GPR110 extracellular fragment 1070:1102 the GPR110 extracellular fragment 1070:1102 These interactions appear to be critical for folding, as removal of the glycosylation site greatly decreases expression of the GPR110 extracellular fragment. 36716818 6 45 theme rigid 721:725 arg1 connections 727:737 rigid connections 721:737 rigid connections between these domains that are stabilized by complementary interfaces 721:807 The structure together with MD simulations reveal rigid connections between these domains that are stabilized by complementary interfaces. 36716818 2 46 theme aGPCR 237:241 arg1 subfamily 243:251 the aGPCR subfamily VI 233:254 the aGPCR subfamily VI 233:254 GPR110 belongs to the aGPCR subfamily VI and was initially identified as an oncogene involved in lung and prostate cancers. 36716818 10 47 theme Stachel 1307:1313 arg1 peptide 1315:1321 the Stachel peptide 1303:1321 the Stachel peptide which in turn redocks to the orthosteric pocket for receptor activation 1303:1393 This suggests that the agonist may function by removing the Stachel peptide which in turn redocks to the orthosteric pocket for receptor activation. 36716818 1 48 theme pivotal 111:117 arg1 role 119:122 a pivotal role 109:122 a pivotal role 109:122 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 7 49 theme extensive 895:903 arg1 contacts 905:912 extensive contacts 895:912 extensive contacts with the preceding HormR domain 895:944 Strikingly, we found N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain. 36716818 1 50 theme other 198:202 arg1 processes 204:212 other processes 198:212 other processes 198:212 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 5 51 theme Å 657:657 arg1 resolution 659:668 2.9 Å resolution 653:668 2.9 Å resolution 653:668 Here, we report the crystal structure of a GPR110 fragment composing the SEA, HormR, and GAIN domains at 2.9 Å resolution. 36716818 9 52 theme ligand 1137:1142 arg1 synaptamide 1144:1154 the ligand synaptamide 1133:1154 the ligand synaptamide 1133:1154 We further demonstrate that the ligand synaptamide fits well within the hydrophobic pocket occupied by the Stachel peptide in the rest state. 36716818 1 53 theme human 127:131 arg1 responses 140:148 human immune responses 127:148 human immune responses 127:148 Adhesion G protein-coupled receptors (aGPCRs) play a pivotal role in human immune responses, cellular communication, organ development, and other processes. 36716818 7 54 theme GAIN 878:881 arg1 domain 883:888 the GAIN domain 874:888 the GAIN domain 874:888 Strikingly, we found N-linked carbohydrates attached to N389 of the GAIN domain form extensive contacts with the preceding HormR domain. 36716818 6 55 theme MD 699:700 arg1 simulations 702:712 MD simulations 699:712 MD simulations 699:712 The structure together with MD simulations reveal rigid connections between these domains that are stabilized by complementary interfaces. 36716818 2 56 theme prostate 321:328 arg1 cancers 330:336 prostate cancers 321:336 prostate cancers 321:336 GPR110 belongs to the aGPCR subfamily VI and was initially identified as an oncogene involved in lung and prostate cancers. 36716818 3 57 theme inter-cellular 420:433 arg1 signaling 435:443 inter-cellular signaling 420:443 inter-cellular signaling 420:443 GPR110 contains tandem adhesion domains at the extracellular region that mediate inter-cellular signaling. 36716818 2 58 dep subfamily 243:251 arg1 VI 253:254 VI 253:254 VI 253:254 GPR110 belongs to the aGPCR subfamily VI and was initially identified as an oncogene involved in lung and prostate cancers. 36716818 8 59 gly glycosylation 1019:1031 arg2 site 1033:1036 the glycosylation site 1015:1036 the glycosylation site 1015:1036 These interactions appear to be critical for folding, as removal of the glycosylation site greatly decreases expression of the GPR110 extracellular fragment. 36584791 0 0 theme homogenous 79:88 arg1 conjugates 104:113 homogenous antibody-drug conjugates 79:113 homogenous antibody-drug conjugates 79:113 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 1 1 theme conjugates 401:410 arg1 preparation 361:371 preparation 361:371 preparation of homogenous antibody-drug conjugates (ADCs) 361:417 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 2 2 theme oxazoline 591:599 arg1 transglycosylation 529:546 one-step enzymatic transglycosylation 510:546 one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody 510:630 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 3 3 theme payload-linked 731:744 arg1 glycan 746:751 a pre-defined payload-linked glycan 717:751 a pre-defined payload-linked glycan 717:751 In this method, a mixture of different glycoforms of the Fc-glycan is replaced with a pre-defined payload-linked glycan. 36584791 2 4 theme one-step 510:517 arg1 transglycosylation 529:546 one-step enzymatic transglycosylation 510:546 one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody 510:630 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 0 5 theme conjugates 104:113 arg1 preparation 64:74 preparation 64:74 preparation of homogenous antibody-drug conjugates 64:113 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 4 6 attach linked 777:782 arg2 payloads 764:771 two payloads 760:771 two payloads 760:771 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 4 6 attach linked 777:782 arg3 substrates 805:814 each donor glycan substrates 787:814 each donor glycan substrates 787:814 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 4 7 theme hydrophobic 933:943 arg1 chromatography 957:970 hydrophobic interaction chromatography analysis and purification 933:996 chromatography 957:970 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 5 8 theme growth 1103:1108 arg1 receptor 1117:1124 epidermal growth factor receptor 2 1093:1126 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 8 theme growth 1103:1108 arg1 anti-her2 1129:1137 anti-her2 1129:1137 anti-her2 1129:1137 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 9 theme Monomethyl 1044:1053 arg1 MMAE 1069:1072 MMAE 1069:1072 MMAE 1069:1072 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 9 theme Monomethyl 1044:1053 arg1 E 1066:1066 Monomethyl auristatin E 1044:1066 Monomethyl auristatin E (MMAE) 1044:1073 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 1 10 theme attractive 301:310 arg1 glycan 234:239 The conserved N-linked glycan 211:239 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies 211:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 1 10 theme attractive 301:310 arg1 target 312:317 an attractive target 298:317 an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs) 298:417 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 0 11 theme antibody-drug 90:102 arg1 conjugates 104:113 homogenous antibody-drug conjugates 79:113 homogenous antibody-drug conjugates 79:113 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 5 12 theme model 1156:1160 arg1 components 1166:1175 the model ADC components 1152:1175 the model ADC components 1152:1175 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 12 theme model 1156:1160 arg1 strategy 1029:1036 this conjugation strategy 1012:1036 this conjugation strategy using Monomethyl auristatin E (MMAE) 1012:1073 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 12 theme model 1156:1160 arg1 antibody 1140:1147 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 6 13 theme ADCs 1343:1346 arg1 preparation 1312:1322 the preparation 1308:1322 the preparation of next generation ADCs 1308:1346 Our novel conjugation strategy, ez-ADiCon, provides a new approach for the preparation of next generation ADCs. 36584791 5 14 theme auristatin 1055:1064 arg1 MMAE 1069:1072 MMAE 1069:1072 MMAE 1069:1072 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 14 theme auristatin 1055:1064 arg1 E 1066:1066 Monomethyl auristatin E 1044:1066 Monomethyl auristatin E (MMAE) 1044:1073 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 0 15 theme one-step 119:126 arg1 transglycosylation 138:155 one-step enzymatic transglycosylation 119:155 one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes 119:208 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 5 16 theme ADC 1162:1164 arg1 components 1166:1175 the model ADC components 1152:1175 the model ADC components 1152:1175 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 16 theme ADC 1162:1164 arg1 strategy 1029:1036 this conjugation strategy 1012:1036 this conjugation strategy using Monomethyl auristatin E (MMAE) 1012:1073 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 16 theme ADC 1162:1164 arg1 antibody 1140:1147 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 1 17 link N-linked 225:232 arg1 glycan 234:239 The conserved N-linked glycan 211:239 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies 211:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 1 17 link N-linked 225:232 arg1 target 312:317 an attractive target 298:317 an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs) 298:417 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 6 18 theme conjugation 1247:1257 arg1 ez-ADiCon 1269:1277 ez-ADiCon 1269:1277 ez-ADiCon 1269:1277 Our novel conjugation strategy, ez-ADiCon, provides a new approach for the preparation of next generation ADCs. 36584791 6 18 theme conjugation 1247:1257 arg1 strategy 1259:1266 Our novel conjugation strategy 1237:1266 Our novel conjugation strategy 1237:1266 Our novel conjugation strategy, ez-ADiCon, provides a new approach for the preparation of next generation ADCs. 36584791 2 19 theme novel 438:442 arg1 strategy 461:468 a novel ADC constructing strategy 436:468 a novel ADC constructing strategy 436:468 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 6 20 theme next 1327:1330 arg1 ADCs 1343:1346 next generation ADCs 1327:1346 next generation ADCs 1327:1346 Our novel conjugation strategy, ez-ADiCon, provides a new approach for the preparation of next generation ADCs. 36584791 4 21 theme efficient 817:825 arg1 conjugation 827:837 efficient conjugation 817:837 efficient conjugation 817:837 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 1 22 theme conserved 215:223 arg1 glycan 234:239 The conserved N-linked glycan 211:239 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies 211:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 1 22 theme conserved 215:223 arg1 target 312:317 an attractive target 298:317 an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs) 298:417 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 4 23 with ADC 870:872 arg1 molecules 896:904 mostly four drug molecules 879:904 mostly four drug molecules per antibody 879:917 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 4 24 theme each 787:790 arg1 substrates 805:814 each donor glycan substrates 787:814 each donor glycan substrates 787:814 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 4 25 theme interaction 945:955 arg1 chromatography 957:970 hydrophobic interaction chromatography analysis and purification 933:996 chromatography 957:970 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 1 26 theme N-linked 225:232 arg1 glycan 234:239 The conserved N-linked glycan 211:239 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies 211:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 1 26 theme N-linked 225:232 arg1 target 312:317 an attractive target 298:317 an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs) 298:417 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 2 27 theme ez-ADiCon 478:486 arg1 " 487:487 ez-ADiCon" 478:487 ez-ADiCon" 478:487 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 6 28 theme generation 1332:1341 arg1 ADCs 1343:1346 next generation ADCs 1327:1346 next generation ADCs 1327:1346 Our novel conjugation strategy, ez-ADiCon, provides a new approach for the preparation of next generation ADCs. 36584791 2 29 gly transglycosylation 529:546 arg1 oxazoline 591:599 a payload-preloaded bi-antennary glycan oxazoline 551:599 a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody 551:630 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 3 30 link payload-linked 731:744 arg1 glycan 746:751 a pre-defined payload-linked glycan 717:751 a pre-defined payload-linked glycan 717:751 In this method, a mixture of different glycoforms of the Fc-glycan is replaced with a pre-defined payload-linked glycan. 36584791 3 31 gly glycoforms 672:681 arg1 Fc-glycan 690:698 the Fc-glycan 686:698 the Fc-glycan 686:698 In this method, a mixture of different glycoforms of the Fc-glycan is replaced with a pre-defined payload-linked glycan. 36584791 0 32 theme novel 13:17 arg1 strategy 42:49 A novel glyco-remodeling based strategy 11:49 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 0:209 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 1 33 theme site-specific 323:335 arg1 conjugation 345:355 site-specific payload conjugation 323:355 site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs) 323:417 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 5 34 dep in 1214:1215 arg1 vitro 1217:1221 vitro 1217:1221 vitro 1217:1221 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 6 35 theme new 1291:1293 arg1 approach 1295:1302 a new approach 1289:1302 a new approach for the preparation of next generation ADCs 1289:1346 Our novel conjugation strategy, ez-ADiCon, provides a new approach for the preparation of next generation ADCs. 36584791 4 36 theme glycan 798:803 arg1 substrates 805:814 each donor glycan substrates 787:814 each donor glycan substrates 787:814 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 5 37 theme conjugation 1017:1027 arg1 strategy 1029:1036 this conjugation strategy 1012:1036 this conjugation strategy using Monomethyl auristatin E (MMAE) 1012:1073 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 37 theme conjugation 1017:1027 arg1 components 1166:1175 the model ADC components 1152:1175 the model ADC components 1152:1175 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 37 theme conjugation 1017:1027 arg1 antibody 1140:1147 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 1 38 theme payload 337:343 arg1 conjugation 345:355 site-specific payload conjugation 323:355 site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs) 323:417 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 0 39 theme enzymatic 128:136 arg1 transglycosylation 138:155 one-step enzymatic transglycosylation 119:155 one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes 119:208 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 3 40 theme Fc-glycan 690:698 arg1 glycoforms 672:681 different glycoforms 662:681 different glycoforms of the Fc-glycan 662:698 In this method, a mixture of different glycoforms of the Fc-glycan is replaced with a pre-defined payload-linked glycan. 36584791 4 41 theme donor 792:796 arg1 substrates 805:814 each donor glycan substrates 787:814 each donor glycan substrates 787:814 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 0 42 theme based 36:40 arg1 strategy 42:49 A novel glyco-remodeling based strategy 11:49 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 0:209 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 4 43 theme drug 891:894 arg1 molecules 896:904 mostly four drug molecules 879:904 mostly four drug molecules per antibody 879:917 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 0 44 theme payload-preloaded 162:178 arg1 complexes 200:208 payload-preloaded bi-antennary glycan complexes 162:208 payload-preloaded bi-antennary glycan complexes 162:208 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 2 45 theme constructing 448:459 arg1 strategy 461:468 a novel ADC constructing strategy 436:468 a novel ADC constructing strategy 436:468 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 5 46 theme anti-Human 1082:1091 arg1 components 1166:1175 the model ADC components 1152:1175 the model ADC components 1152:1175 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 46 theme anti-Human 1082:1091 arg1 antibody 1140:1147 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 46 theme anti-Human 1082:1091 arg1 strategy 1029:1036 this conjugation strategy 1012:1036 this conjugation strategy using Monomethyl auristatin E (MMAE) 1012:1073 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 1 47 theme Fc 248:249 arg1 antibodies 284:293 recombinant monoclonal antibodies 261:293 recombinant monoclonal antibodies 261:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 1 47 theme Fc 248:249 arg1 domain 251:256 the Fc domain 244:256 the Fc domain of recombinant monoclonal antibodies 244:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 0 48 theme glyco-remodeling 19:34 arg1 strategy 42:49 A novel glyco-remodeling based strategy 11:49 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 0:209 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 2 49 theme glycan 584:589 arg1 oxazoline 591:599 a payload-preloaded bi-antennary glycan oxazoline 551:599 a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody 551:630 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 4 50 theme homogenous 859:868 arg1 ADC 870:872 a highly homogenous ADC 850:872 a highly homogenous ADC with mostly four drug molecules per antibody 850:917 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 2 51 theme ADC 444:446 arg1 strategy 461:468 a novel ADC constructing strategy 436:468 a novel ADC constructing strategy 436:468 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 2 52 theme bi-antennary 571:582 arg1 oxazoline 591:599 a payload-preloaded bi-antennary glycan oxazoline 551:599 a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody 551:630 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 0 53 theme glycan 193:198 arg1 complexes 200:208 payload-preloaded bi-antennary glycan complexes 162:208 payload-preloaded bi-antennary glycan complexes 162:208 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 4 54 dep chromatography 957:970 arg1 analysis 972:979 analysis 972:979 analysis 972:979 Since two payloads are linked on each donor glycan substrates, efficient conjugation results in a highly homogenous ADC with mostly four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. 36584791 2 55 theme payload-preloaded 553:569 arg1 oxazoline 591:599 a payload-preloaded bi-antennary glycan oxazoline 551:599 a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody 551:630 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 1 56 from domain 251:256 arg1 glycan 234:239 The conserved N-linked glycan 211:239 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies 211:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 1 56 from domain 251:256 arg1 target 312:317 an attractive target 298:317 an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs) 298:417 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 5 57 theme target-specific 1198:1212 arg1 cytotoxicity 1223:1234 its target-specific in vitro cytotoxicity 1194:1234 its target-specific in vitro cytotoxicity 1194:1234 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 58 theme in 1214:1215 arg1 cytotoxicity 1223:1234 its target-specific in vitro cytotoxicity 1194:1234 its target-specific in vitro cytotoxicity 1194:1234 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 0 59 theme bi-antennary 180:191 arg1 complexes 200:208 payload-preloaded bi-antennary glycan complexes 162:208 payload-preloaded bi-antennary glycan complexes 162:208 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 5 60 theme receptor 1117:1124 arg1 components 1166:1175 the model ADC components 1152:1175 the model ADC components 1152:1175 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 60 theme receptor 1117:1124 arg1 antibody 1140:1147 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 60 theme receptor 1117:1124 arg1 strategy 1029:1036 this conjugation strategy 1012:1036 this conjugation strategy using Monomethyl auristatin E (MMAE) 1012:1073 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 61 theme factor 1110:1115 arg1 receptor 1117:1124 epidermal growth factor receptor 2 1093:1126 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 61 theme factor 1110:1115 arg1 anti-her2 1129:1137 anti-her2 1129:1137 anti-her2 1129:1137 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 1 62 theme homogenous 376:385 arg1 ADCs 413:416 ADCs 413:416 ADCs 413:416 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 1 62 theme homogenous 376:385 arg1 conjugates 401:410 homogenous antibody-drug conjugates 376:410 homogenous antibody-drug conjugates (ADCs) 376:417 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 3 63 theme pre-defined 719:729 arg1 glycan 746:751 a pre-defined payload-linked glycan 717:751 a pre-defined payload-linked glycan 717:751 In this method, a mixture of different glycoforms of the Fc-glycan is replaced with a pre-defined payload-linked glycan. 36584791 3 64 theme different 662:670 arg1 glycoforms 672:681 different glycoforms 662:681 different glycoforms of the Fc-glycan 662:698 In this method, a mixture of different glycoforms of the Fc-glycan is replaced with a pre-defined payload-linked glycan. 36584791 5 65 theme epidermal 1093:1101 arg1 receptor 1117:1124 epidermal growth factor receptor 2 1093:1126 an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody 1079:1147 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 5 65 theme epidermal 1093:1101 arg1 anti-her2 1129:1137 anti-her2 1129:1137 anti-her2 1129:1137 We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. 36584791 2 66 gly deglycosylated 608:621 arg1 antibody 623:630 a deglycosylated antibody 606:630 a deglycosylated antibody 606:630 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 2 67 theme deglycosylated 608:621 arg1 antibody 623:630 a deglycosylated antibody 606:630 a deglycosylated antibody 606:630 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 3 68 theme glycoforms 672:681 arg1 mixture 651:657 a mixture 649:657 a mixture of different glycoforms of the Fc-glycan 649:698 In this method, a mixture of different glycoforms of the Fc-glycan is replaced with a pre-defined payload-linked glycan. 36584791 0 69 with transglycosylation 138:155 arg1 complexes 200:208 payload-preloaded bi-antennary glycan complexes 162:208 payload-preloaded bi-antennary glycan complexes 162:208 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 1 70 theme recombinant 261:271 arg1 antibodies 284:293 recombinant monoclonal antibodies 261:293 recombinant monoclonal antibodies 261:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 6 71 theme novel 1241:1245 arg1 ez-ADiCon 1269:1277 ez-ADiCon 1269:1277 ez-ADiCon 1269:1277 Our novel conjugation strategy, ez-ADiCon, provides a new approach for the preparation of next generation ADCs. 36584791 6 71 theme novel 1241:1245 arg1 strategy 1259:1266 Our novel conjugation strategy 1237:1266 Our novel conjugation strategy 1237:1266 Our novel conjugation strategy, ez-ADiCon, provides a new approach for the preparation of next generation ADCs. 36584791 1 72 theme monoclonal 273:282 arg1 antibodies 284:293 recombinant monoclonal antibodies 261:293 recombinant monoclonal antibodies 261:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 2 73 theme enzymatic 519:527 arg1 transglycosylation 529:546 one-step enzymatic transglycosylation 510:546 one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody 510:630 Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. 36584791 1 74 theme antibody-drug 387:399 arg1 ADCs 413:416 ADCs 413:416 ADCs 413:416 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 1 74 theme antibody-drug 387:399 arg1 conjugates 401:410 homogenous antibody-drug conjugates 376:410 homogenous antibody-drug conjugates (ADCs) 376:417 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 0 75 dep ez-ADiCon 0:8 arg1 strategy 42:49 A novel glyco-remodeling based strategy 11:49 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 0:209 ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes. 36584791 1 76 theme antibodies 284:293 arg1 antibodies 284:293 recombinant monoclonal antibodies 261:293 recombinant monoclonal antibodies 261:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 36584791 1 76 theme antibodies 284:293 arg1 domain 251:256 the Fc domain 244:256 the Fc domain of recombinant monoclonal antibodies 244:293 The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). 37148271 0 0 theme Ervogastat 167:176 arg1 Discovery 131:139 the Discovery 127:139 the Discovery of the Clinical Candidate Ervogastat 127:176 Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat. 37148271 7 1 theme azetidine 1536:1544 arg1 substituent 1546:1556 the azetidine substituent 1532:1556 the azetidine substituent 1532:1556 Replacement of the azetidine substituent with a pyridine ring furnished 8, which mitigated the formation of the electrophilic aldehyde metabolite, and was a more potent DGAT2 inhibitor than 2. 37148271 1 2 with liabilities 329:339 arg1 PF-06427878 381:391 the liver-targeted DGAT2 inhibitor PF-06427878 346:391 the liver-targeted DGAT2 inhibitor PF-06427878 346:391 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 1 3 theme acyltransferase 278:292 arg1 inhibitors 249:258 systemically acting, amide-based inhibitors 216:258 systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) 216:302 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 5 4 from Inclusion 1041:1049 arg1 incubations 1089:1099 microsomal incubations 1078:1099 microsomal incubations 1078:1099 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 4 5 theme M6 969:970 arg1 formation 930:938 the formation 926:938 the formation of ketone (M2) and aldehyde (M6) 926:971 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 6 6 theme human 1376:1380 arg1 incubations 1399:1409 NADPH- and l-cysteine-fortified human liver microsomal incubations 1344:1409 NADPH- and l-cysteine-fortified human liver microsomal incubations with 2 1344:1416 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 8 7 theme metabolic 1809:1817 arg1 stability 1819:1827 greater metabolic stability 1801:1827 greater metabolic stability 1801:1827 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 1 8 theme SAR 201:203 arg1 studies 205:211 SAR studies 201:211 SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878 201:391 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 7 9 theme DGAT2 1686:1690 arg1 inhibitor 1692:1700 a more potent DGAT2 inhibitor 1672:1700 a more potent DGAT2 inhibitor than 2 1672:1707 Replacement of the azetidine substituent with a pyridine ring furnished 8, which mitigated the formation of the electrophilic aldehyde metabolite, and was a more potent DGAT2 inhibitor than 2. 37148271 2 10 theme piperidine 580:589 arg1 oxidation 596:604 extensive piperidine ring oxidation 570:604 extensive piperidine ring oxidation 570:604 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 3 11 theme ring 649:652 arg1 modifications 654:666 Piperidine ring modifications 638:666 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination 638:730 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination led to azetidine 2 that demonstrated lower intrinsic clearance. 37148271 1 12 from studies 205:211 arg1 inhibitors 249:258 systemically acting, amide-based inhibitors 216:258 systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) 216:302 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 1 13 dep acting 229:234 arg1 amide-based 237:247 amide-based 237:247 amide-based 237:247 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 4 14 theme aldehyde 959:966 arg1 M6 969:970 aldehyde (M6) 959:971 aldehyde (M6) 959:971 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 3 15 theme alternate 676:684 arg1 combination 720:730 alternate N-linked heterocyclic ring/spacer combination 676:730 alternate N-linked heterocyclic ring/spacer combination 676:730 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination led to azetidine 2 that demonstrated lower intrinsic clearance. 37148271 0 16 theme Clinical 148:155 arg1 Ervogastat 167:176 the Clinical Candidate Ervogastat 144:176 the Clinical Candidate Ervogastat 144:176 Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat. 37148271 3 17 theme N-linked 686:693 arg1 combination 720:730 alternate N-linked heterocyclic ring/spacer combination 676:730 alternate N-linked heterocyclic ring/spacer combination 676:730 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination led to azetidine 2 that demonstrated lower intrinsic clearance. 37148271 6 18 with incubations 1399:1409 arg1 2 1416:1416 2 1416:1416 2 1416:1416 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 4 19 dep underwent 807:815 arg1 followed 876:883 followed 876:883 followed by azetidine ring scission 876:910 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 4 20 theme liver 1023:1027 arg1 microsomes 1029:1038 NADPH-supplemented human liver microsomes 998:1038 NADPH-supplemented human liver microsomes 998:1038 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 2 21 theme dialkoxyaromatic 448:463 arg1 ring 465:468 the dialkoxyaromatic ring 444:468 the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation 444:516 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 6 22 theme proposed 1423:1430 arg1 structures 1443:1452 proposed metabolite structures 1423:1452 proposed metabolite structures 1423:1452 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 0 23 theme Bioactivation 13:25 arg1 Liability 27:35 a Bioactivation Liability 11:35 a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat 11:176 Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat. 37148271 8 24 theme PF-06865571 1854:1864 arg1 discovery 1841:1849 the discovery 1837:1849 the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis 1837:1972 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 2 25 theme intrinsic 529:537 arg1 clearance 539:547 metabolic intrinsic clearance 519:547 metabolic intrinsic clearance 519:547 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 7 26 theme aldehyde 1643:1650 arg1 metabolite 1652:1661 the electrophilic aldehyde metabolite 1625:1661 the electrophilic aldehyde metabolite 1625:1661 Replacement of the azetidine substituent with a pyridine ring furnished 8, which mitigated the formation of the electrophilic aldehyde metabolite, and was a more potent DGAT2 inhibitor than 2. 37148271 2 27 theme metabolic 519:527 arg1 clearance 539:547 metabolic intrinsic clearance 519:547 metabolic intrinsic clearance 519:547 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 5 28 theme aldehyde 1284:1291 arg1 M6 1293:1294 aldehyde M6 1284:1294 aldehyde M6 1284:1294 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 0 29 theme Acyltransferase 89:103 arg1 Inhibitor 61:69 an Azetidine-Based Inhibitor 42:69 an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat 42:176 Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat. 37148271 1 30 theme liver-targeted 350:363 arg1 PF-06427878 381:391 the liver-targeted DGAT2 inhibitor PF-06427878 346:391 the liver-targeted DGAT2 inhibitor PF-06427878 346:391 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 8 31 from refinements 1729:1739 arg1 8 1744:1744 8 1744:1744 8 1744:1744 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 1 32 theme inhibitor 371:379 arg1 PF-06427878 381:391 the liver-targeted DGAT2 inhibitor PF-06427878 346:391 the liver-targeted DGAT2 inhibitor PF-06427878 346:391 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 4 33 theme NADPH-supplemented 998:1015 arg1 microsomes 1029:1038 NADPH-supplemented human liver microsomes 998:1038 NADPH-supplemented human liver microsomes 998:1038 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 6 34 theme microsomal 1388:1397 arg1 incubations 1399:1409 NADPH- and l-cysteine-fortified human liver microsomal incubations 1344:1409 NADPH- and l-cysteine-fortified human liver microsomal incubations with 2 1344:1416 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 5 35 theme Cys-thiazolidine 1152:1167 arg1 conjugates 1198:1207 Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates 1125:1207 Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates 1125:1207 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 0 36 theme Diacylglycerol 74:87 arg1 Acyltransferase 89:103 Diacylglycerol Acyltransferase 2 74:105 Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat 74:176 Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat. 37148271 0 36 theme Diacylglycerol 74:87 arg1 DGAT2 108:112 DGAT2 108:112 DGAT2 108:112 Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat. 37148271 6 37 theme two-dimensional 1483:1497 arg1 spectroscopy 1503:1514 one- and two-dimensional NMR spectroscopy 1474:1514 one- and two-dimensional NMR spectroscopy 1474:1514 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 5 38 theme conjugates 1198:1207 arg1 formation 1112:1120 the formation 1108:1120 the formation 1108:1120 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 8 39 theme phase 1900:1904 arg1 trials 1917:1922 phase 2 clinical trials 1900:1922 phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis 1900:1972 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 4 40 theme cytochrome 826:835 arg1 CYP 843:845 CYP 843:845 CYP 843:845 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 4 40 theme cytochrome 826:835 arg1 P450 837:840 a facile cytochrome P450 817:840 a facile cytochrome P450 (CYP) 817:846 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 6 41 theme one- 1474:1477 arg1 spectroscopy 1503:1514 one- and two-dimensional NMR spectroscopy 1474:1514 one- and two-dimensional NMR spectroscopy 1474:1514 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 4 42 theme azetidine 888:896 arg1 scission 903:910 azetidine ring scission 888:910 azetidine ring scission 888:910 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 2 43 theme atom 436:439 arg1 placement 412:420 strategic placement 402:420 strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation 402:516 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 5 44 theme semicarbazone 1179:1191 arg1 conjugates 1198:1207 Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates 1125:1207 Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates 1125:1207 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 2 45 from placement 412:420 arg1 ring 465:468 the dialkoxyaromatic ring 444:468 the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation 444:516 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 3 46 theme ring/spacer 708:718 arg1 combination 720:730 alternate N-linked heterocyclic ring/spacer combination 676:730 alternate N-linked heterocyclic ring/spacer combination 676:730 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination led to azetidine 2 that demonstrated lower intrinsic clearance. 37148271 0 47 theme Azetidine-Based 45:59 arg1 Inhibitor 61:69 an Azetidine-Based Inhibitor 42:69 an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat 42:176 Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat. 37148271 1 48 theme metabolic 319:327 arg1 liabilities 329:339 metabolic liabilities 319:339 metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878 319:391 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 4 49 theme α-carbon 857:864 arg1 oxidation 866:874 a facile cytochrome P450 (CYP)-mediated α-carbon oxidation 817:874 a facile cytochrome P450 (CYP)-mediated α-carbon oxidation 817:874 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 8 50 theme bond 1778:1781 arg1 substituents 1783:1794 amide bond substituents 1772:1794 amide bond substituents with greater metabolic stability 1772:1827 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 5 51 with agents 1272:1277 arg1 M6 1293:1294 aldehyde M6 1284:1294 aldehyde M6 1284:1294 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 8 52 theme Further 1710:1716 arg1 refinements 1729:1739 Further structural refinements 1710:1739 Further structural refinements 1710:1739 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 5 53 theme trapping 1263:1270 arg1 agents 1272:1277 the nucleophilic trapping agents 1246:1277 the nucleophilic trapping agents with aldehyde M6 1246:1294 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 7 54 theme substituent 1546:1556 arg1 Replacement 1517:1527 Replacement 1517:1527 Replacement of the azetidine substituent with a pyridine ring 1517:1577 Replacement of the azetidine substituent with a pyridine ring furnished 8, which mitigated the formation of the electrophilic aldehyde metabolite, and was a more potent DGAT2 inhibitor than 2. 37148271 8 55 theme clinical 1908:1915 arg1 trials 1917:1922 phase 2 clinical trials 1900:1922 phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis 1900:1972 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 3 56 theme lower 769:773 arg1 clearance 785:793 lower intrinsic clearance 769:793 lower intrinsic clearance 769:793 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination led to azetidine 2 that demonstrated lower intrinsic clearance. 37148271 1 57 theme diacylglycerol 263:276 arg1 DGAT2 297:301 DGAT2 297:301 DGAT2 297:301 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 1 57 theme diacylglycerol 263:276 arg1 acyltransferase 278:292 diacylglycerol acyltransferase 2 263:294 diacylglycerol acyltransferase 2 (DGAT2) 263:302 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 6 58 dep Metabolites 1297:1307 arg1 M2 1309:1310 M2 1309:1310 M2 1309:1310 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 6 58 dep Metabolites 1297:1307 arg1 Metabolites 1297:1307 Metabolites M2 and M5 1297:1317 Metabolites M2 and M5 1297:1317 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 6 58 dep Metabolites 1297:1307 arg1 M5 1316:1317 M5 1316:1317 M5 1316:1317 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 4 59 theme ketone 943:948 arg1 M2 951:952 ketone (M2) 943:953 ketone (M2) 943:953 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 8 60 theme nonalcoholic 1945:1956 arg1 steatohepatitis 1958:1972 nonalcoholic steatohepatitis 1945:1972 nonalcoholic steatohepatitis 1945:1972 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 8 61 theme amide 1772:1776 arg1 substituents 1783:1794 amide bond substituents 1772:1794 amide bond substituents with greater metabolic stability 1772:1827 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 6 62 theme liver 1382:1386 arg1 incubations 1399:1409 NADPH- and l-cysteine-fortified human liver microsomal incubations 1344:1409 NADPH- and l-cysteine-fortified human liver microsomal incubations with 2 1344:1416 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 7 63 theme potent 1679:1684 arg1 inhibitor 1692:1700 a more potent DGAT2 inhibitor 1672:1700 a more potent DGAT2 inhibitor than 2 1672:1707 Replacement of the azetidine substituent with a pyridine ring furnished 8, which mitigated the formation of the electrophilic aldehyde metabolite, and was a more potent DGAT2 inhibitor than 2. 37148271 2 64 theme ring 591:594 arg1 oxidation 596:604 extensive piperidine ring oxidation 570:604 extensive piperidine ring oxidation 570:604 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 6 65 theme l-cysteine-fortified 1355:1374 arg1 incubations 1399:1409 NADPH- and l-cysteine-fortified human liver microsomal incubations 1344:1409 NADPH- and l-cysteine-fortified human liver microsomal incubations with 2 1344:1416 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 5 66 theme Cys-Gly-thiazolidine 1125:1144 arg1 conjugates 1198:1207 Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates 1125:1207 Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates 1125:1207 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 3 67 theme Piperidine 638:647 arg1 modifications 654:666 Piperidine ring modifications 638:666 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination 638:730 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination led to azetidine 2 that demonstrated lower intrinsic clearance. 37148271 8 68 theme greater 1801:1807 arg1 stability 1819:1827 greater metabolic stability 1801:1827 greater metabolic stability 1801:1827 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 2 69 theme extensive 570:578 arg1 oxidation 596:604 extensive piperidine ring oxidation 570:604 extensive piperidine ring oxidation 570:604 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 6 70 theme NADPH- 1344:1349 arg1 incubations 1399:1409 NADPH- and l-cysteine-fortified human liver microsomal incubations 1344:1409 NADPH- and l-cysteine-fortified human liver microsomal incubations with 2 1344:1416 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 4 71 theme M2 951:952 arg1 formation 930:938 the formation 926:938 the formation of ketone (M2) and aldehyde (M6) 926:971 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 0 72 theme Candidate 157:165 arg1 Ervogastat 167:176 the Clinical Candidate Ervogastat 144:176 the Clinical Candidate Ervogastat 144:176 Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat. 37148271 4 73 from metabolites 983:993 arg1 microsomes 1029:1038 NADPH-supplemented human liver microsomes 998:1038 NADPH-supplemented human liver microsomes 998:1038 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 7 74 theme metabolite 1652:1661 arg1 formation 1612:1620 the formation 1608:1620 the formation of the electrophilic aldehyde metabolite 1608:1661 Replacement of the azetidine substituent with a pyridine ring furnished 8, which mitigated the formation of the electrophilic aldehyde metabolite, and was a more potent DGAT2 inhibitor than 2. 37148271 5 75 attach derived 1221:1227 arg1 reaction 1234:1241 reaction 1234:1241 reaction of the nucleophilic trapping agents with aldehyde M6 1234:1294 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 5 75 attach derived 1221:1227 arg2 formation 1112:1120 the formation 1108:1120 the formation 1108:1120 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 6 76 theme metabolite 1432:1441 arg1 structures 1443:1452 proposed metabolite structures 1423:1452 proposed metabolite structures 1423:1452 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 7 77 theme electrophilic 1629:1641 arg1 metabolite 1652:1661 the electrophilic aldehyde metabolite 1625:1661 the electrophilic aldehyde metabolite 1625:1661 Replacement of the azetidine substituent with a pyridine ring furnished 8, which mitigated the formation of the electrophilic aldehyde metabolite, and was a more potent DGAT2 inhibitor than 2. 37148271 4 78 theme human 1017:1021 arg1 microsomes 1029:1038 NADPH-supplemented human liver microsomes 998:1038 NADPH-supplemented human liver microsomes 998:1038 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 2 79 from ring 465:468 arg1 PF-06427878 473:483 PF-06427878 473:483 PF-06427878 473:483 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 8 80 theme steatohepatitis 1958:1972 arg1 treatment 1932:1940 the treatment 1928:1940 the treatment of nonalcoholic steatohepatitis 1928:1972 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 1 81 theme DGAT2 365:369 arg1 PF-06427878 381:391 the liver-targeted DGAT2 inhibitor PF-06427878 346:391 the liver-targeted DGAT2 inhibitor PF-06427878 346:391 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 4 82 theme stable 976:981 arg1 metabolites 983:993 stable metabolites 976:993 stable metabolites in NADPH-supplemented human liver microsomes 976:1038 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 8 83 theme structural 1718:1727 arg1 refinements 1729:1739 Further structural refinements 1710:1739 Further structural refinements 1710:1739 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 1 84 theme acting 229:234 arg1 inhibitors 249:258 systemically acting, amide-based inhibitors 216:258 systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) 216:302 We recently disclosed SAR studies on systemically acting, amide-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) that addressed metabolic liabilities with the liver-targeted DGAT2 inhibitor PF-06427878. 37148271 6 85 theme NMR 1499:1501 arg1 spectroscopy 1503:1514 one- and two-dimensional NMR spectroscopy 1474:1514 one- and two-dimensional NMR spectroscopy 1474:1514 Metabolites M2 and M5 were biosynthesized from NADPH- and l-cysteine-fortified human liver microsomal incubations with 2, and proposed metabolite structures were verified using one- and two-dimensional NMR spectroscopy. 37148271 8 86 with substituents 1783:1794 arg1 stability 1819:1827 greater metabolic stability 1801:1827 greater metabolic stability 1801:1827 Further structural refinements in 8, specifically introducing amide bond substituents with greater metabolic stability, led to the discovery of PF-06865571 (ervogastat) that is currently in phase 2 clinical trials for the treatment of nonalcoholic steatohepatitis. 37148271 2 87 theme strategic 402:410 arg1 placement 412:420 strategic placement 402:420 strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation 402:516 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 3 88 link N-linked 686:693 arg1 combination 720:730 alternate N-linked heterocyclic ring/spacer combination 676:730 alternate N-linked heterocyclic ring/spacer combination 676:730 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination led to azetidine 2 that demonstrated lower intrinsic clearance. 37148271 4 89 theme facile 819:824 arg1 CYP 843:845 CYP 843:845 CYP 843:845 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 4 89 theme facile 819:824 arg1 P450 837:840 a facile cytochrome P450 817:840 a facile cytochrome P450 (CYP) 817:846 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 5 90 theme semicarbazide 1061:1073 arg1 Inclusion 1041:1049 Inclusion 1041:1049 Inclusion of GSH or semicarbazide in microsomal incubations 1041:1099 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 2 91 theme oxidative 494:502 arg1 O-dearylation 504:516 oxidative O-dearylation 494:516 oxidative O-dearylation 494:516 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 3 92 theme heterocyclic 695:706 arg1 combination 720:730 alternate N-linked heterocyclic ring/spacer combination 676:730 alternate N-linked heterocyclic ring/spacer combination 676:730 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination led to azetidine 2 that demonstrated lower intrinsic clearance. 37148271 0 93 with Liability 27:35 arg1 Inhibitor 61:69 an Azetidine-Based Inhibitor 42:69 an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat 42:176 Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat. 37148271 2 94 theme nitrogen 427:434 arg1 atom 436:439 a nitrogen atom 425:439 a nitrogen atom 425:439 Despite strategic placement of a nitrogen atom in the dialkoxyaromatic ring in PF-06427878 to evade oxidative O-dearylation, metabolic intrinsic clearance remained high due to extensive piperidine ring oxidation as exemplified with compound 1. 37148271 5 95 theme microsomal 1078:1087 arg1 incubations 1089:1099 microsomal incubations 1078:1099 microsomal incubations 1078:1099 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 4 96 theme ring 898:901 arg1 scission 903:910 azetidine ring scission 888:910 azetidine ring scission 888:910 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 4 97 theme -mediated 847:855 arg1 oxidation 866:874 a facile cytochrome P450 (CYP)-mediated α-carbon oxidation 817:874 a facile cytochrome P450 (CYP)-mediated α-carbon oxidation 817:874 However, 2 underwent a facile cytochrome P450 (CYP)-mediated α-carbon oxidation followed by azetidine ring scission, resulting in the formation of ketone (M2) and aldehyde (M6) as stable metabolites in NADPH-supplemented human liver microsomes. 37148271 7 98 with Replacement 1517:1527 arg1 ring 1574:1577 a pyridine ring 1563:1577 a pyridine ring 1563:1577 Replacement of the azetidine substituent with a pyridine ring furnished 8, which mitigated the formation of the electrophilic aldehyde metabolite, and was a more potent DGAT2 inhibitor than 2. 37148271 5 99 theme nucleophilic 1250:1261 arg1 agents 1272:1277 the nucleophilic trapping agents 1246:1277 the nucleophilic trapping agents with aldehyde M6 1246:1294 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 7 100 theme pyridine 1565:1572 arg1 ring 1574:1577 a pyridine ring 1563:1577 a pyridine ring 1563:1577 Replacement of the azetidine substituent with a pyridine ring furnished 8, which mitigated the formation of the electrophilic aldehyde metabolite, and was a more potent DGAT2 inhibitor than 2. 37148271 5 101 theme GSH 1054:1056 arg1 Inclusion 1041:1049 Inclusion 1041:1049 Inclusion of GSH or semicarbazide in microsomal incubations 1041:1099 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 37148271 3 102 theme intrinsic 775:783 arg1 clearance 785:793 lower intrinsic clearance 769:793 lower intrinsic clearance 769:793 Piperidine ring modifications through alternate N-linked heterocyclic ring/spacer combination led to azetidine 2 that demonstrated lower intrinsic clearance. 37148271 5 103 theme agents 1272:1277 arg1 reaction 1234:1241 reaction 1234:1241 reaction of the nucleophilic trapping agents with aldehyde M6 1234:1294 Inclusion of GSH or semicarbazide in microsomal incubations led to the formation of Cys-Gly-thiazolidine (M3), Cys-thiazolidine (M5), and semicarbazone (M7) conjugates, which were derived from reaction of the nucleophilic trapping agents with aldehyde M6. 36403203 0 0 theme antibody 77:84 arg1 cocktail 86:93 an antibody cocktail 74:93 an antibody cocktail 74:93 A novel plant-made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant. 36403203 6 1 theme plants 1303:1308 arg1 potential 1290:1298 the potential 1286:1298 the potential of plants 1286:1308 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 4 2 theme Omicron 805:811 arg1 RBD 814:816 the B.1.1.529 (Omicron) RBD 790:816 the B.1.1.529 (Omicron) RBD 790:816 Of note, 11D7 maintains recognition against the B.1.1.529 (Omicron) RBD, as well neutralizing activity. 36403203 1 3 theme mouse 225:229 arg1 immunization 231:242 mouse immunization 225:242 mouse immunization 225:242 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 2 4 theme greater 516:522 arg1 safety 536:541 safety 536:541 safety 536:541 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 2 4 theme greater 516:522 arg1 therapeutic 548:558 therapeutic 548:558 therapeutic 548:558 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 2 4 theme greater 516:522 arg1 potency 524:530 greater potency 516:530 greater potency 516:530 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 5 5 theme Omicron 1060:1066 arg1 variant 1068:1074 the Omicron variant 1056:1074 the Omicron variant 1056:1074 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 1 6 theme novel 158:162 arg1 mAb 199:201 mAb 199:201 mAb 199:201 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 1 6 theme novel 158:162 arg1 11D7 205:208 11D7 205:208 11D7 205:208 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 1 6 theme novel 158:162 arg1 antibody 189:196 neutralizing monoclonal antibody 165:196 neutralizing monoclonal antibody (mAb) 165:202 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 6 7 theme alternative 1348:1358 arg1 platform 1360:1367 an economic and safety-friendly alternative platform 1316:1367 an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis 1316:1429 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 2 8 dep human-like 440:449 arg1 homogenous 459:468 homogenous 459:468 homogenous 459:468 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 5 9 theme novel 885:889 arg1 mAb 891:893 this novel mAb 880:893 this novel mAb 880:893 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 0 10 theme cocktail 86:93 arg1 potency 63:69 the synergetic potency 48:69 the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant 48:132 A novel plant-made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant. 36403203 3 11 theme RBD-binding 677:687 arg1 it 661:662 it 661:662 it 661:662 The epitope of 11D7 was mapped by competitive binding with well-characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. 36403203 3 11 theme RBD-binding 677:687 arg1 mAb 689:691 a Class 4 RBD-binding mAb 667:691 a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site 667:743 The epitope of 11D7 was mapped by competitive binding with well-characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. 36403203 6 12 theme developed 1188:1196 arg1 mAbs 1210:1213 developed therapeutic mAbs 1188:1213 developed therapeutic mAbs 1188:1213 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 1 13 theme hybridoma 248:256 arg1 generation 258:267 hybridoma generation 248:267 hybridoma generation 248:267 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 0 14 theme SARS-CoV-2 107:116 arg1 variant 126:132 the SARS-CoV-2 Omicron variant 103:132 the SARS-CoV-2 Omicron variant 103:132 A novel plant-made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant. 36403203 2 15 theme chimeric 358:365 arg1 IgG 373:375 a chimeric human IgG 356:375 a chimeric human IgG 356:375 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 3 16 theme Class 669:673 arg1 it 661:662 it 661:662 it 661:662 The epitope of 11D7 was mapped by competitive binding with well-characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. 36403203 3 16 theme Class 669:673 arg1 mAb 689:691 a Class 4 RBD-binding mAb 667:691 a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site 667:743 The epitope of 11D7 was mapped by competitive binding with well-characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. 36403203 6 17 theme safety-friendly 1332:1346 arg1 platform 1360:1367 an economic and safety-friendly alternative platform 1316:1367 an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis 1316:1429 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 1 18 theme neutralizing 165:176 arg1 mAb 199:201 mAb 199:201 mAb 199:201 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 1 18 theme neutralizing 165:176 arg1 11D7 205:208 11D7 205:208 11D7 205:208 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 1 18 theme neutralizing 165:176 arg1 antibody 189:196 neutralizing monoclonal antibody 165:196 neutralizing monoclonal antibody (mAb) 165:202 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 0 19 theme novel 2:6 arg1 antibody 30:37 A novel plant-made monoclonal antibody 0:37 A novel plant-made monoclonal antibody 0:37 A novel plant-made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant. 36403203 6 20 dep typical 1174:1180 arg1 typical 1174:1180 typical 1174:1180 typical 1174:1180 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 6 20 dep typical 1174:1180 arg1 mechanism 1152:1160 a mechanism 1150:1160 a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis 1150:1429 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 6 20 dep typical 1174:1180 arg1 highlights 1275:1284 highlights 1275:1284 highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis 1275:1429 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 4 21 theme B.1.1.529 794:802 arg1 RBD 814:816 the B.1.1.529 (Omicron) RBD 790:816 the B.1.1.529 (Omicron) RBD 790:816 Of note, 11D7 maintains recognition against the B.1.1.529 (Omicron) RBD, as well neutralizing activity. 36403203 1 22 theme monoclonal 178:187 arg1 mAb 199:201 mAb 199:201 mAb 199:201 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 1 22 theme monoclonal 178:187 arg1 11D7 205:208 11D7 205:208 11D7 205:208 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 1 22 theme monoclonal 178:187 arg1 antibody 189:196 neutralizing monoclonal antibody 165:196 neutralizing monoclonal antibody (mAb) 165:202 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 6 23 theme benthamiana 1255:1265 arg1 plants 1267:1272 ΔXFT Nicotiana benthamiana plants 1240:1272 ΔXFT Nicotiana benthamiana plants 1240:1272 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 0 24 theme monoclonal 19:28 arg1 antibody 30:37 A novel plant-made monoclonal antibody 0:37 A novel plant-made monoclonal antibody 0:37 A novel plant-made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant. 36403203 0 25 theme plant-made 8:17 arg1 antibody 30:37 A novel plant-made monoclonal antibody 0:37 A novel plant-made monoclonal antibody 0:37 A novel plant-made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant. 36403203 0 26 theme Omicron 118:124 arg1 variant 126:132 the SARS-CoV-2 Omicron variant 103:132 the SARS-CoV-2 Omicron variant 103:132 A novel plant-made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant. 36403203 3 27 with binding 607:613 arg1 mAbs 639:642 well-characterized mAbs 620:642 well-characterized mAbs 620:642 The epitope of 11D7 was mapped by competitive binding with well-characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. 36403203 2 28 theme human-like 440:449 arg1 glycans 479:485 human-like, highly homogenous N-linked glycans 440:485 human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic 440:558 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 6 29 theme Nicotiana 1245:1253 arg1 plants 1267:1272 ΔXFT Nicotiana benthamiana plants 1240:1272 ΔXFT Nicotiana benthamiana plants 1240:1272 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 6 30 theme evolving 1404:1411 arg1 crisis 1424:1429 the evolving SARS-CoV-2 crisis 1400:1429 the evolving SARS-CoV-2 crisis 1400:1429 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 1 31 theme parental 282:289 arg1 RBD 302:304 the parental Wuhan-Hu-1 RBD 278:304 the parental Wuhan-Hu-1 RBD of SARS-CoV-2 278:318 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 6 32 theme ΔXFT 1240:1243 arg1 plants 1267:1272 ΔXFT Nicotiana benthamiana plants 1240:1272 ΔXFT Nicotiana benthamiana plants 1240:1272 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 5 33 contain containing 994:1003 arg2 antibodies 1009:1018 the antibodies tixagevimab and cilgavimab, against the Omicron variant 1005:1074 antibodies 1009:1018 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 5 33 contain containing 994:1003 arg2 tixagevimab 1020:1030 tixagevimab 1020:1030 tixagevimab 1020:1030 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 5 33 contain containing 994:1003 arg1 Evusheld™ 984:992 Evusheld™ 984:992 Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant 984:1074 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 5 33 contain containing 994:1003 arg2 cilgavimab 1036:1045 cilgavimab 1036:1045 cilgavimab 1036:1045 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 0 34 theme synergetic 52:61 arg1 potency 63:69 the synergetic potency 48:69 the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant 48:132 A novel plant-made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant. 36403203 1 35 theme Wuhan-Hu-1 291:300 arg1 RBD 302:304 the parental Wuhan-Hu-1 RBD 278:304 the parental Wuhan-Hu-1 RBD of SARS-CoV-2 278:318 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 3 36 theme competitive 595:605 arg1 binding 607:613 competitive binding 595:613 competitive binding with well-characterized mAbs 595:642 The epitope of 11D7 was mapped by competitive binding with well-characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. 36403203 5 37 theme established 944:954 arg1 cocktails 965:973 established antibody cocktails 944:973 established antibody cocktails 944:973 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 5 37 theme established 944:954 arg1 Evusheld™ 984:992 Evusheld™ 984:992 Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant 984:1074 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 5 38 theme antibody 956:963 arg1 cocktails 965:973 established antibody cocktails 944:973 established antibody cocktails 944:973 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 5 38 theme antibody 956:963 arg1 Evusheld™ 984:992 Evusheld™ 984:992 Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant 984:1074 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 2 39 link N-linked 470:477 arg1 glycans 479:485 human-like, highly homogenous N-linked glycans 440:485 human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic 440:558 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 6 40 theme therapeutic 1198:1208 arg1 mAbs 1210:1213 developed therapeutic mAbs 1188:1213 developed therapeutic mAbs 1188:1213 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 5 41 theme additional 922:931 arg1 synergy 933:939 additional synergy 922:939 additional synergy 922:939 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 4 42 theme neutralizing 827:838 arg1 activity 840:847 neutralizing activity 827:847 neutralizing activity 827:847 Of note, 11D7 maintains recognition against the B.1.1.529 (Omicron) RBD, as well neutralizing activity. 36403203 3 43 theme well-characterized 620:637 arg1 mAbs 639:642 well-characterized mAbs 620:642 well-characterized mAbs 620:642 The epitope of 11D7 was mapped by competitive binding with well-characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. 36403203 6 44 theme unique 1103:1108 arg1 mAb 1110:1112 a unique mAb 1101:1112 a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis 1101:1429 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 6 44 theme unique 1103:1108 arg1 11D7 1093:1096 11D7 1093:1096 11D7 1093:1096 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 6 45 theme SARS-CoV-2 1413:1422 arg1 crisis 1424:1429 the evolving SARS-CoV-2 crisis 1400:1429 the evolving SARS-CoV-2 crisis 1400:1429 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 5 46 dep antibodies 1009:1018 arg1 cilgavimab 1036:1045 cilgavimab 1036:1045 cilgavimab 1036:1045 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 5 46 dep antibodies 1009:1018 arg1 tixagevimab 1020:1030 tixagevimab 1020:1030 tixagevimab 1020:1030 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 5 46 dep antibodies 1009:1018 arg1 antibodies 1009:1018 the antibodies tixagevimab and cilgavimab, against the Omicron variant 1005:1074 antibodies 1009:1018 We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. 36403203 2 47 theme N-linked 470:477 arg1 glycans 479:485 human-like, highly homogenous N-linked glycans 440:485 human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic 440:558 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 2 48 theme human 367:371 arg1 IgG 373:375 a chimeric human IgG 356:375 a chimeric human IgG 356:375 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 3 49 theme binding 732:738 arg1 site 740:743 the ACE2 binding site 723:743 the ACE2 binding site 723:743 The epitope of 11D7 was mapped by competitive binding with well-characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. 36403203 6 50 theme economic 1319:1326 arg1 platform 1360:1367 an economic and safety-friendly alternative platform 1316:1367 an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis 1316:1429 Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis. 36403203 1 51 theme SARS-CoV-2 309:318 arg1 RBD 302:304 the parental Wuhan-Hu-1 RBD 278:304 the parental Wuhan-Hu-1 RBD of SARS-CoV-2 278:318 This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. 36403203 3 52 theme 11D7 576:579 arg1 epitope 565:571 The epitope 561:571 The epitope of 11D7 561:579 The epitope of 11D7 was mapped by competitive binding with well-characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. 36403203 2 53 contain has 492:494 arg2 potential 496:504 potential 496:504 potential to impart greater potency and safety as a therapeutic 496:558 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 2 53 contain has 492:494 arg1 glycans 479:485 human-like, highly homogenous N-linked glycans 440:485 human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic 440:558 We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. 36403203 3 54 theme ACE2 727:730 arg1 site 740:743 the ACE2 binding site 723:743 the ACE2 binding site 723:743 The epitope of 11D7 was mapped by competitive binding with well-characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. 36279778 6 0 theme strenuous 917:925 arg1 process 927:933 this strenuous process 912:933 this strenuous process 912:933 Despite decades of use, this strenuous process remains unchanged, utilizing toxic reagents and extended sample preparation time. 36279778 2 1 theme acid 338:341 arg1 position 343:350 amino acid position 297 332:354 amino acid position 297 of the heavy chain 332:373 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 9 2 theme labeled 1461:1467 arg1 method 1469:1474 the conventional fluorescent labeled method 1432:1474 the conventional fluorescent labeled method 1432:1474 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 9 2 theme labeled 1461:1467 arg1 results 1421:1427 similar quantitative results 1400:1427 similar quantitative results 1400:1427 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 0 3 theme aerosol 65:71 arg1 detection 73:81 charged aerosol detection 57:81 charged aerosol detection 57:81 Development of a novel, label-free N-glycan method using charged aerosol detection. 36279778 7 4 theme fluorescent 1135:1145 arg1 labeling 1147:1154 fluorescent labeling 1135:1154 fluorescent labeling 1135:1154 As an intervention, this report showcases a novel, label-free approach to detect and quantify N-glycans without using fluorescent labeling. 36279778 8 5 theme glycans 1247:1253 arg1 detection 1218:1226 detection 1218:1226 detection of non-derivatized glycans 1218:1253 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 2 6 theme amino 332:336 arg1 position 343:350 amino acid position 297 332:354 amino acid position 297 of the heavy chain 332:373 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 8 7 theme charged 1261:1267 arg1 detector 1277:1284 charged aerosol detector 1261:1284 charged aerosol detector 1261:1284 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 3 8 theme quality 510:516 arg1 panel 528:532 the critical quality attribute panel 497:532 the critical quality attribute panel for release testing 497:552 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 4 9 theme N-linked 570:577 arg1 glycans 579:585 N-linked glycans 570:585 N-linked glycans 570:585 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 4 10 theme glycans 727:733 arg1 labeling 701:708 fluorescent labeling 689:708 fluorescent labeling of the liberated glycans 689:733 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 6 11 theme use 907:909 arg1 decades 896:902 decades 896:902 decades of use 896:909 Despite decades of use, this strenuous process remains unchanged, utilizing toxic reagents and extended sample preparation time. 36279778 2 12 theme asparagine 282:291 arg1 region 322:327 the Fc region 315:327 the Fc region 315:327 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 12 theme asparagine 282:291 arg1 N-X-S/T 303:309 N-X-S/T 303:309 N-X-S/T 303:309 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 12 theme asparagine 282:291 arg1 residues 293:300 conserved asparagine residues 272:300 conserved asparagine residues (N-X-S/T) of the Fc region 272:327 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 9 13 theme method 1508:1513 arg1 validity 1492:1499 the validity 1488:1499 the validity of the method for product release 1488:1533 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 6 14 theme sample 992:997 arg1 preparation 999:1009 extended sample preparation 983:1009 extended sample preparation time 983:1014 Despite decades of use, this strenuous process remains unchanged, utilizing toxic reagents and extended sample preparation time. 36279778 8 15 theme PGC 1196:1198 arg1 column 1200:1205 mixed-mode PGC column 1185:1205 mixed-mode PGC column 1185:1205 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 4 16 gly glycoproteins 605:617 arg1 glycoproteins 605:617 glycoproteins 605:617 glycoproteins 605:617 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 3 17 theme serum 441:445 arg1 half-life 447:455 serum half-life 441:455 serum half-life 441:455 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 2 18 theme conserved 272:280 arg1 region 322:327 the Fc region 315:327 the Fc region 315:327 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 18 theme conserved 272:280 arg1 N-X-S/T 303:309 N-X-S/T 303:309 N-X-S/T 303:309 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 18 theme conserved 272:280 arg1 residues 293:300 conserved asparagine residues 272:300 conserved asparagine residues (N-X-S/T) of the Fc region 272:327 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 19 theme chain 369:373 arg1 position 343:350 amino acid position 297 332:354 amino acid position 297 of the heavy chain 332:373 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 5 20 theme liquid 793:798 arg1 HILIC 816:820 HILIC 816:820 HILIC 816:820 The labeled glycans are then separated using hydrophilic liquid chromatography (HILIC) with fluorescence detection to generate chromatographic profile. 36279778 5 20 theme liquid 793:798 arg1 chromatography 800:813 hydrophilic liquid chromatography 781:813 hydrophilic liquid chromatography (HILIC) with fluorescence detection 781:849 The labeled glycans are then separated using hydrophilic liquid chromatography (HILIC) with fluorescence detection to generate chromatographic profile. 36279778 3 21 theme critical 501:508 arg1 panel 528:532 the critical quality attribute panel 497:532 the critical quality attribute panel for release testing 497:552 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 2 22 theme heavy 363:367 arg1 chain 369:373 the heavy chain 359:373 the heavy chain 359:373 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 6 23 theme toxic 964:968 arg1 reagents 970:977 toxic reagents 964:977 toxic reagents 964:977 Despite decades of use, this strenuous process remains unchanged, utilizing toxic reagents and extended sample preparation time. 36279778 5 24 theme labeled 740:746 arg1 glycans 748:754 The labeled glycans 736:754 The labeled glycans 736:754 The labeled glycans are then separated using hydrophilic liquid chromatography (HILIC) with fluorescence detection to generate chromatographic profile. 36279778 3 25 theme release 538:544 arg1 testing 546:552 release testing 538:552 release testing 538:552 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 4 26 theme PNGase 667:672 arg1 F 674:674 PNGase F 667:674 PNGase F 667:674 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 2 27 gly glycosylated 256:267 arg1 MAbs 247:250 MAbs 247:250 MAbs 247:250 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 27 gly glycosylated 256:267 arg2 N-X-S/T 303:309 N-X-S/T 303:309 N-X-S/T 303:309 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 27 gly glycosylated 256:267 arg2 position 343:350 amino acid position 297 332:354 amino acid position 297 of the heavy chain 332:373 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 27 gly glycosylated 256:267 arg2 residues 293:300 conserved asparagine residues 272:300 conserved asparagine residues (N-X-S/T) of the Fc region 272:327 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 27 gly glycosylated 256:267 arg2 region 322:327 the Fc region 315:327 the Fc region 315:327 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 6 28 theme extended 983:990 arg1 preparation 999:1009 extended sample preparation 983:1009 extended sample preparation time 983:1014 Despite decades of use, this strenuous process remains unchanged, utilizing toxic reagents and extended sample preparation time. 36279778 1 29 theme Monoclonal 84:93 arg1 mAbs 107:110 mAbs 107:110 mAbs 107:110 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 1 29 theme Monoclonal 84:93 arg1 antibodies 95:104 Monoclonal antibodies 84:104 Monoclonal antibodies (mAbs) 84:111 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 1 29 theme Monoclonal 84:93 arg1 glycoproteins 125:137 complex glycoproteins 117:137 complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases 117:244 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 1 30 theme various 175:181 arg1 indications 195:205 various therapeutic indications 175:205 various therapeutic indications such as cancer and autoimmune diseases 175:244 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 1 30 theme various 175:181 arg1 cancer 215:220 cancer 215:220 cancer 215:220 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 1 30 theme various 175:181 arg1 diseases 237:244 autoimmune diseases 226:244 autoimmune diseases 226:244 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 0 31 theme novel 17:21 arg1 method 44:49 a novel, label-free N-glycan method 15:49 a novel, label-free N-glycan method 15:49 Development of a novel, label-free N-glycan method using charged aerosol detection. 36279778 7 32 dep novel 1061:1065 arg1 label-free 1068:1077 label-free 1068:1077 label-free 1068:1077 As an intervention, this report showcases a novel, label-free approach to detect and quantify N-glycans without using fluorescent labeling. 36279778 3 33 theme panel 528:532 arg1 part 489:492 part 489:492 part of the critical quality attribute panel for release testing 489:552 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 1 34 theme therapeutic 183:193 arg1 indications 195:205 various therapeutic indications 175:205 various therapeutic indications such as cancer and autoimmune diseases 175:244 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 1 34 theme therapeutic 183:193 arg1 cancer 215:220 cancer 215:220 cancer 215:220 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 1 34 theme therapeutic 183:193 arg1 diseases 237:244 autoimmune diseases 226:244 autoimmune diseases 226:244 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 4 35 theme liberated 717:725 arg1 glycans 727:733 the liberated glycans 713:733 the liberated glycans 713:733 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 8 36 theme glycans 1171:1177 arg1 Separation 1157:1166 Separation 1157:1166 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans 1157:1253 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 8 37 theme cost 1355:1358 arg1 savings 1360:1366 significant cost savings 1343:1366 significant cost savings 1343:1366 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 1 38 theme indications 195:205 arg1 treatment 162:170 treatment 162:170 treatment of various therapeutic indications such as cancer and autoimmune diseases 162:244 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 8 39 theme non-derivatized 1231:1245 arg1 glycans 1247:1253 non-derivatized glycans 1231:1253 non-derivatized glycans 1231:1253 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 3 40 theme therapeutics 468:479 arg1 efficacy 428:435 efficacy 428:435 efficacy 428:435 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 3 40 theme therapeutics 468:479 arg1 half-life 447:455 serum half-life 441:455 serum half-life 441:455 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 7 41 theme novel 1061:1065 arg1 intervention 1023:1034 an intervention 1020:1034 an intervention 1020:1034 As an intervention, this report showcases a novel, label-free approach to detect and quantify N-glycans without using fluorescent labeling. 36279778 7 41 theme novel 1061:1065 arg1 approach 1079:1086 a novel, label-free approach 1059:1086 a novel, label-free approach to detect and quantify N-glycans without using fluorescent labeling 1059:1154 As an intervention, this report showcases a novel, label-free approach to detect and quantify N-glycans without using fluorescent labeling. 36279778 9 42 theme product 1519:1525 arg1 release 1527:1533 product release 1519:1533 product release 1519:1533 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 8 43 theme aerosol 1269:1275 arg1 detector 1277:1284 charged aerosol detector 1261:1284 charged aerosol detector 1261:1284 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 5 44 theme chromatographic 863:877 arg1 profile 879:885 chromatographic profile 863:885 chromatographic profile 863:885 The labeled glycans are then separated using hydrophilic liquid chromatography (HILIC) with fluorescence detection to generate chromatographic profile. 36279778 4 45 with digestion 652:660 arg1 F 674:674 PNGase F 667:674 PNGase F 667:674 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 9 46 theme conventional 1436:1447 arg1 method 1469:1474 the conventional fluorescent labeled method 1432:1474 the conventional fluorescent labeled method 1432:1474 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 9 46 theme conventional 1436:1447 arg1 results 1421:1427 similar quantitative results 1400:1427 similar quantitative results 1400:1427 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 3 47 theme efficacy 428:435 arg1 functions 415:423 the functions 411:423 the functions of efficacy and serum half-life of protein therapeutics 411:479 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 0 48 theme method 44:49 arg1 Development 0:10 Development 0:10 Development of a novel, label-free N-glycan method 0:49 Development of a novel, label-free N-glycan method using charged aerosol detection. 36279778 9 49 theme similar 1400:1406 arg1 method 1469:1474 the conventional fluorescent labeled method 1432:1474 the conventional fluorescent labeled method 1432:1474 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 9 49 theme similar 1400:1406 arg1 results 1421:1427 similar quantitative results 1400:1427 similar quantitative results 1400:1427 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 8 50 theme mixed-mode 1185:1194 arg1 column 1200:1205 mixed-mode PGC column 1185:1205 mixed-mode PGC column 1185:1205 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 4 51 attach released 591:598 arg1 glycoproteins 605:617 glycoproteins 605:617 glycoproteins 605:617 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 4 51 attach released 591:598 arg2 glycans 579:585 N-linked glycans 570:585 N-linked glycans 570:585 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 5 52 theme fluorescence 828:839 arg1 detection 841:849 fluorescence detection 828:849 fluorescence detection 828:849 The labeled glycans are then separated using hydrophilic liquid chromatography (HILIC) with fluorescence detection to generate chromatographic profile. 36279778 3 53 theme protein 460:466 arg1 therapeutics 468:479 protein therapeutics 460:479 protein therapeutics 460:479 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 0 54 theme N-glycan 35:42 arg1 method 44:49 a novel, label-free N-glycan method 15:49 a novel, label-free N-glycan method 15:49 Development of a novel, label-free N-glycan method using charged aerosol detection. 36279778 9 55 theme quantitative 1408:1419 arg1 method 1469:1474 the conventional fluorescent labeled method 1432:1474 the conventional fluorescent labeled method 1432:1474 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 9 55 theme quantitative 1408:1419 arg1 results 1421:1427 similar quantitative results 1400:1427 similar quantitative results 1400:1427 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 1 56 gly glycoproteins 125:137 arg1 antibodies 95:104 Monoclonal antibodies 84:104 Monoclonal antibodies (mAbs) 84:111 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 1 56 gly glycoproteins 125:137 arg1 glycoproteins 125:137 complex glycoproteins 117:137 complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases 117:244 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 4 57 link N-linked 570:577 arg1 glycans 579:585 N-linked glycans 570:585 N-linked glycans 570:585 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 4 58 dep released 591:598 arg1 followed 677:684 followed 677:684 followed by fluorescent labeling of the liberated glycans 677:733 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 2 59 theme region 322:327 arg1 region 322:327 the Fc region 315:327 the Fc region 315:327 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 59 theme region 322:327 arg1 N-X-S/T 303:309 N-X-S/T 303:309 N-X-S/T 303:309 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 2 59 theme region 322:327 arg1 residues 293:300 conserved asparagine residues 272:300 conserved asparagine residues (N-X-S/T) of the Fc region 272:327 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 4 60 with denaturation 625:636 arg1 F 674:674 PNGase F 667:674 PNGase F 667:674 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 0 61 dep novel 17:21 arg1 label-free 24:33 label-free 24:33 label-free 24:33 Development of a novel, label-free N-glycan method using charged aerosol detection. 36279778 9 62 theme label-free 1373:1382 arg1 method 1384:1389 The label-free method 1369:1389 The label-free method 1369:1389 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 2 63 theme Fc 319:320 arg1 region 322:327 the Fc region 315:327 the Fc region 315:327 MAbs are glycosylated at conserved asparagine residues (N-X-S/T) of the Fc region at amino acid position 297 of the heavy chain. 36279778 5 64 with chromatography 800:813 arg1 detection 841:849 fluorescence detection 828:849 fluorescence detection 828:849 The labeled glycans are then separated using hydrophilic liquid chromatography (HILIC) with fluorescence detection to generate chromatographic profile. 36279778 6 65 theme preparation 999:1009 arg1 time 1011:1014 extended sample preparation time 983:1014 extended sample preparation time 983:1014 Despite decades of use, this strenuous process remains unchanged, utilizing toxic reagents and extended sample preparation time. 36279778 8 66 theme significant 1343:1353 arg1 savings 1360:1366 significant cost savings 1343:1366 significant cost savings 1343:1366 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 1 67 theme complex 117:123 arg1 antibodies 95:104 Monoclonal antibodies 84:104 Monoclonal antibodies (mAbs) 84:111 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 1 67 theme complex 117:123 arg1 glycoproteins 125:137 complex glycoproteins 117:137 complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases 117:244 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 3 68 theme half-life 447:455 arg1 functions 415:423 the functions 411:423 the functions of efficacy and serum half-life of protein therapeutics 411:479 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 0 69 theme charged 57:63 arg1 detection 73:81 charged aerosol detection 57:81 charged aerosol detection 57:81 Development of a novel, label-free N-glycan method using charged aerosol detection. 36279778 8 70 theme turnaround 1299:1308 arg1 time 1310:1313 the overall turnaround time 1287:1313 the overall turnaround time 1287:1313 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 8 71 theme overall 1291:1297 arg1 time 1310:1313 the overall turnaround time 1287:1313 the overall turnaround time 1287:1313 Separation of glycans using mixed-mode PGC column along with detection of non-derivatized glycans using charged aerosol detector, the overall turnaround time can be greatly reduced with significant cost savings. 36279778 3 72 dep panel 528:532 arg1 attribute 518:526 attribute 518:526 attribute 518:526 Glycans are important in governing the functions of efficacy and serum half-life of protein therapeutics and are part of the critical quality attribute panel for release testing. 36279778 4 73 theme enzymatic 642:650 arg1 digestion 652:660 enzymatic digestion 642:660 enzymatic digestion with PNGase F 642:674 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 36279778 1 74 theme autoimmune 226:235 arg1 diseases 237:244 autoimmune diseases 226:244 autoimmune diseases 226:244 Monoclonal antibodies (mAbs) are complex glycoproteins that are developed for treatment of various therapeutic indications such as cancer and autoimmune diseases. 36279778 5 75 theme hydrophilic 781:791 arg1 HILIC 816:820 HILIC 816:820 HILIC 816:820 The labeled glycans are then separated using hydrophilic liquid chromatography (HILIC) with fluorescence detection to generate chromatographic profile. 36279778 5 75 theme hydrophilic 781:791 arg1 chromatography 800:813 hydrophilic liquid chromatography 781:813 hydrophilic liquid chromatography (HILIC) with fluorescence detection 781:849 The labeled glycans are then separated using hydrophilic liquid chromatography (HILIC) with fluorescence detection to generate chromatographic profile. 36279778 9 76 theme fluorescent 1449:1459 arg1 method 1469:1474 the conventional fluorescent labeled method 1432:1474 the conventional fluorescent labeled method 1432:1474 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 9 76 theme fluorescent 1449:1459 arg1 results 1421:1427 similar quantitative results 1400:1427 similar quantitative results 1400:1427 The label-free method provides similar quantitative results as the conventional fluorescent labeled method, confirming the validity of the method for product release. 36279778 4 77 theme fluorescent 689:699 arg1 labeling 701:708 fluorescent labeling 689:708 fluorescent labeling of the liberated glycans 689:733 Traditionally, N-linked glycans are released from glycoproteins after denaturation and enzymatic digestion with PNGase F, followed by fluorescent labeling of the liberated glycans. 35484013 0 0 theme type 120:123 arg1 N-glycans 125:133 multi-branched complex type N-glycans 97:133 multi-branched complex type N-glycans 97:133 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 35484013 3 1 theme multibranched 373:385 arg1 N-glycans 400:408 multibranched complex-type N-glycans 373:408 multibranched complex-type N-glycans 373:408 However, there are still a few enzymes that have hydrolytic activity toward multibranched complex-type N-glycans on glycoproteins. 35484013 7 2 theme liquid 693:698 arg1 chromatography 700:713 High performance liquid chromatography 676:713 High performance liquid chromatography (HPLC) analysis 676:729 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 7 2 theme liquid 693:698 arg1 HPLC 716:719 HPLC 716:719 HPLC 716:719 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 8 3 theme different 938:946 arg1 glycoproteins 948:960 different glycoproteins 938:960 different glycoproteins from high-mannose type to complex-type oligosaccharides 938:1016 The hydrolytic activities of Endo-BN were also tested on different glycoproteins from high-mannose type to complex-type oligosaccharides. 35484013 7 4 theme α2,6-linked 820:830 arg1 residues 844:851 α2,6-linked sialic acid residues 820:851 α2,6-linked sialic acid residues 820:851 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 0 5 theme complex 112:118 arg1 N-glycans 125:133 multi-branched complex type N-glycans 97:133 multi-branched complex type N-glycans 97:133 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 35484013 1 6 theme N-linked 209:216 arg1 oligosaccharides 218:233 the N-linked oligosaccharides 205:233 the N-linked oligosaccharides 205:233 Endo-β-N-acetylglucosaminidases (ENGases) are enzymes that hydrolyze the N-linked oligosaccharides. 35484013 8 7 theme high-mannose 967:978 arg1 oligosaccharides 1001:1016 high-mannose type to complex-type oligosaccharides 967:1016 high-mannose type to complex-type oligosaccharides 967:1016 The hydrolytic activities of Endo-BN were also tested on different glycoproteins from high-mannose type to complex-type oligosaccharides. 35484013 7 8 theme sialic 832:837 arg1 residues 844:851 α2,6-linked sialic acid residues 820:851 α2,6-linked sialic acid residues 820:851 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 0 9 from Characterization 0:15 arg1 nordii 74:79 Bacteroides nordii 62:79 Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans 62:133 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 35484013 7 10 link α2,6-linked 820:830 arg1 residues 844:851 α2,6-linked sialic acid residues 820:851 α2,6-linked sialic acid residues 820:851 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 8 11 theme Endo-BN 910:916 arg1 activities 896:905 The hydrolytic activities 881:905 The hydrolytic activities of Endo-BN 881:916 The hydrolytic activities of Endo-BN were also tested on different glycoproteins from high-mannose type to complex-type oligosaccharides. 35484013 7 12 theme chromatography 700:713 arg1 analysis 722:729 High performance liquid chromatography (HPLC) analysis 676:729 High performance liquid chromatography (HPLC) analysis 676:729 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 4 13 theme nordii 477:482 arg1 species 494:500 Bacteroides nordii (Endo-BN) species 465:500 Bacteroides nordii (Endo-BN) species 465:500 In this study, one novel ENGase from Bacteroides nordii (Endo-BN) species was identified and characterized. 35484013 4 13 theme nordii 477:482 arg1 Endo-BN 485:491 Endo-BN 485:491 Endo-BN 485:491 In this study, one novel ENGase from Bacteroides nordii (Endo-BN) species was identified and characterized. 35484013 7 14 theme High 676:679 arg1 chromatography 700:713 High performance liquid chromatography 676:713 High performance liquid chromatography (HPLC) analysis 676:729 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 7 14 theme High 676:679 arg1 HPLC 716:719 HPLC 716:719 HPLC 716:719 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 9 15 theme α1-acid 1068:1074 arg1 glycoprotein 1076:1087 α1-acid glycoprotein 1068:1087 α1-acid glycoprotein 1068:1087 The reaction with human transferrin, fetuin, and α1-acid glycoprotein subsequently showed that Endo-BN is capable of releasing multi-branched complex-type N-glycans from these glycoproteins. 35484013 0 16 from nordii 74:79 arg1 Characterization 0:15 Characterization 0:15 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 0:134 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 35484013 0 16 from nordii 74:79 arg1 endo-β-N-acetylglucosaminidase 26:55 novel endo-β-N-acetylglucosaminidase 20:55 novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans 20:133 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 35484013 9 17 gly glycoproteins 1195:1207 arg1 glycoproteins 1195:1207 these glycoproteins 1189:1207 these glycoproteins 1189:1207 The reaction with human transferrin, fetuin, and α1-acid glycoprotein subsequently showed that Endo-BN is capable of releasing multi-branched complex-type N-glycans from these glycoproteins. 35484013 4 18 theme Bacteroides 465:475 arg1 species 494:500 Bacteroides nordii (Endo-BN) species 465:500 Bacteroides nordii (Endo-BN) species 465:500 In this study, one novel ENGase from Bacteroides nordii (Endo-BN) species was identified and characterized. 35484013 4 18 theme Bacteroides 465:475 arg1 Endo-BN 485:491 Endo-BN 485:491 Endo-BN 485:491 In this study, one novel ENGase from Bacteroides nordii (Endo-BN) species was identified and characterized. 35484013 3 19 contain have 341:344 arg1 enzymes 328:334 a few enzymes 322:334 a few enzymes that have hydrolytic activity toward multibranched complex-type N-glycans on glycoproteins 322:425 However, there are still a few enzymes that have hydrolytic activity toward multibranched complex-type N-glycans on glycoproteins. 35484013 3 19 contain have 341:344 arg2 activity 357:364 hydrolytic activity 346:364 hydrolytic activity toward multibranched complex-type N-glycans 346:408 However, there are still a few enzymes that have hydrolytic activity toward multibranched complex-type N-glycans on glycoproteins. 35484013 9 20 with reaction 1023:1030 arg1 fetuin 1056:1061 fetuin 1056:1061 fetuin 1056:1061 The reaction with human transferrin, fetuin, and α1-acid glycoprotein subsequently showed that Endo-BN is capable of releasing multi-branched complex-type N-glycans from these glycoproteins. 35484013 9 20 with reaction 1023:1030 arg1 transferrin 1043:1053 human transferrin 1037:1053 human transferrin 1037:1053 The reaction with human transferrin, fetuin, and α1-acid glycoprotein subsequently showed that Endo-BN is capable of releasing multi-branched complex-type N-glycans from these glycoproteins. 35484013 9 20 with reaction 1023:1030 arg1 glycoprotein 1076:1087 α1-acid glycoprotein 1068:1087 α1-acid glycoprotein 1068:1087 The reaction with human transferrin, fetuin, and α1-acid glycoprotein subsequently showed that Endo-BN is capable of releasing multi-branched complex-type N-glycans from these glycoproteins. 35484013 6 21 theme optimum 637:643 arg1 activity 656:663 optimum hydrolytic activity 637:663 optimum hydrolytic activity 637:663 This Endo-BN exhibited optimum hydrolytic activity at pH 4.0. 35484013 7 22 theme performance 681:691 arg1 chromatography 700:713 High performance liquid chromatography 676:713 High performance liquid chromatography (HPLC) analysis 676:729 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 7 22 theme performance 681:691 arg1 HPLC 716:719 HPLC 716:719 HPLC 716:719 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 8 23 gly glycoproteins 948:960 arg1 glycoproteins 948:960 different glycoproteins 938:960 different glycoproteins from high-mannose type to complex-type oligosaccharides 938:1016 The hydrolytic activities of Endo-BN were also tested on different glycoproteins from high-mannose type to complex-type oligosaccharides. 35484013 8 24 dep oligosaccharides 1001:1016 arg1 to 985:986 to 985:986 to 985:986 The hydrolytic activities of Endo-BN were also tested on different glycoproteins from high-mannose type to complex-type oligosaccharides. 35484013 3 25 theme complex-type 387:398 arg1 N-glycans 400:408 multibranched complex-type N-glycans 373:408 multibranched complex-type N-glycans 373:408 However, there are still a few enzymes that have hydrolytic activity toward multibranched complex-type N-glycans on glycoproteins. 35484013 9 26 theme human 1037:1041 arg1 transferrin 1043:1053 human transferrin 1037:1053 human transferrin 1037:1053 The reaction with human transferrin, fetuin, and α1-acid glycoprotein subsequently showed that Endo-BN is capable of releasing multi-branched complex-type N-glycans from these glycoproteins. 35484013 8 27 theme complex-type 988:999 arg1 oligosaccharides 1001:1016 high-mannose type to complex-type oligosaccharides 967:1016 high-mannose type to complex-type oligosaccharides 967:1016 The hydrolytic activities of Endo-BN were also tested on different glycoproteins from high-mannose type to complex-type oligosaccharides. 35484013 4 28 theme novel 447:451 arg1 ENGase 453:458 one novel ENGase 443:458 one novel ENGase from Bacteroides nordii (Endo-BN) species 443:500 In this study, one novel ENGase from Bacteroides nordii (Endo-BN) species was identified and characterized. 35484013 0 29 theme endo-β-N-acetylglucosaminidase 26:55 arg1 Characterization 0:15 Characterization 0:15 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 0:134 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 35484013 0 30 theme novel 20:24 arg1 endo-β-N-acetylglucosaminidase 26:55 novel endo-β-N-acetylglucosaminidase 20:55 novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans 20:133 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 35484013 1 31 link N-linked 209:216 arg1 oligosaccharides 218:233 the N-linked oligosaccharides 205:233 the N-linked oligosaccharides 205:233 Endo-β-N-acetylglucosaminidases (ENGases) are enzymes that hydrolyze the N-linked oligosaccharides. 35484013 5 32 theme recombinant 540:550 arg1 protein 552:558 The recombinant protein 536:558 The recombinant protein 536:558 The recombinant protein was prepared and expressed in Escherichia coli cells. 35484013 0 33 theme Bacteroides 62:72 arg1 nordii 74:79 Bacteroides nordii 62:79 Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans 62:133 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 35484013 8 34 theme type 980:983 arg1 oligosaccharides 1001:1016 high-mannose type to complex-type oligosaccharides 967:1016 high-mannose type to complex-type oligosaccharides 967:1016 The hydrolytic activities of Endo-BN were also tested on different glycoproteins from high-mannose type to complex-type oligosaccharides. 35484013 8 35 theme hydrolytic 885:894 arg1 activities 896:905 The hydrolytic activities 881:905 The hydrolytic activities of Endo-BN 881:916 The hydrolytic activities of Endo-BN were also tested on different glycoproteins from high-mannose type to complex-type oligosaccharides. 35484013 2 36 theme Many 236:239 arg1 ENGases 241:247 Many ENGases 236:247 Many ENGases 236:247 Many ENGases have already been identified and characterized. 35484013 8 37 from oligosaccharides 1001:1016 arg1 glycoproteins 948:960 different glycoproteins 938:960 different glycoproteins from high-mannose type to complex-type oligosaccharides 938:1016 The hydrolytic activities of Endo-BN were also tested on different glycoproteins from high-mannose type to complex-type oligosaccharides. 35484013 5 38 dep Escherichia 590:600 arg1 coli 602:605 coli 602:605 coli 602:605 The recombinant protein was prepared and expressed in Escherichia coli cells. 35484013 9 39 theme multi-branched 1146:1159 arg1 N-glycans 1174:1182 multi-branched complex-type N-glycans 1146:1182 multi-branched complex-type N-glycans 1146:1182 The reaction with human transferrin, fetuin, and α1-acid glycoprotein subsequently showed that Endo-BN is capable of releasing multi-branched complex-type N-glycans from these glycoproteins. 35484013 3 40 theme few 324:326 arg1 enzymes 328:334 a few enzymes 322:334 a few enzymes that have hydrolytic activity toward multibranched complex-type N-glycans on glycoproteins 322:425 However, there are still a few enzymes that have hydrolytic activity toward multibranched complex-type N-glycans on glycoproteins. 35484013 7 41 theme complex-type 778:789 arg1 N-glycans 791:799 core-fucosylated complex-type N-glycans 761:799 core-fucosylated complex-type N-glycans 761:799 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 6 42 theme hydrolytic 645:654 arg1 activity 656:663 optimum hydrolytic activity 637:663 optimum hydrolytic activity 637:663 This Endo-BN exhibited optimum hydrolytic activity at pH 4.0. 35484013 4 43 from species 494:500 arg1 ENGase 453:458 one novel ENGase 443:458 one novel ENGase from Bacteroides nordii (Endo-BN) species 443:500 In this study, one novel ENGase from Bacteroides nordii (Endo-BN) species was identified and characterized. 35484013 3 44 gly glycoproteins 413:425 arg1 glycoproteins 413:425 glycoproteins 413:425 glycoproteins 413:425 However, there are still a few enzymes that have hydrolytic activity toward multibranched complex-type N-glycans on glycoproteins. 35484013 7 45 theme non-reducing 862:873 arg1 ends 875:878 their non-reducing ends 856:878 their non-reducing ends 856:878 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 7 46 gly core-fucosylated 761:776 arg1 N-glycans 791:799 core-fucosylated complex-type N-glycans 761:799 core-fucosylated complex-type N-glycans 761:799 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 7 47 theme core-fucosylated 761:776 arg1 N-glycans 791:799 core-fucosylated complex-type N-glycans 761:799 core-fucosylated complex-type N-glycans 761:799 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 9 48 theme complex-type 1161:1172 arg1 N-glycans 1174:1182 multi-branched complex-type N-glycans 1146:1182 multi-branched complex-type N-glycans 1146:1182 The reaction with human transferrin, fetuin, and α1-acid glycoprotein subsequently showed that Endo-BN is capable of releasing multi-branched complex-type N-glycans from these glycoproteins. 35484013 3 49 theme hydrolytic 346:355 arg1 activity 357:364 hydrolytic activity 346:364 hydrolytic activity toward multibranched complex-type N-glycans 346:408 However, there are still a few enzymes that have hydrolytic activity toward multibranched complex-type N-glycans on glycoproteins. 35484013 0 50 theme multi-branched 97:110 arg1 N-glycans 125:133 multi-branched complex type N-glycans 97:133 multi-branched complex type N-glycans 97:133 Characterization of novel endo-β-N-acetylglucosaminidase from Bacteroides nordii that hydrolyzes multi-branched complex type N-glycans. 35484013 5 51 theme Escherichia 590:600 arg1 cells 607:611 Escherichia coli cells 590:611 Escherichia coli cells 590:611 The recombinant protein was prepared and expressed in Escherichia coli cells. 35484013 7 52 theme acid 839:842 arg1 residues 844:851 α2,6-linked sialic acid residues 820:851 α2,6-linked sialic acid residues 820:851 High performance liquid chromatography (HPLC) analysis showed that Endo-BN preferred core-fucosylated complex-type N-glycans, with galactose or α2,6-linked sialic acid residues at their non-reducing ends. 35484013 9 53 gly glycoprotein 1076:1087 arg1 glycoprotein 1076:1087 α1-acid glycoprotein 1068:1087 α1-acid glycoprotein 1068:1087 The reaction with human transferrin, fetuin, and α1-acid glycoprotein subsequently showed that Endo-BN is capable of releasing multi-branched complex-type N-glycans from these glycoproteins. 35301302 1 0 theme high 161:164 arg1 area 183:186 high specific surface area 161:186 high specific surface area 161:186 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 2 1 dep induced 457:463 arg1 vapor 451:455 vapor 451:455 vapor 451:455 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 6 2 theme metal-free 1152:1161 arg1 COFs 1163:1166 metal-free COFs 1152:1166 metal-free COFs 1152:1166 When employed as catalysts in hydrogen evolution reaction (HER), they show high electrocatalytic activity compared with metal-free COFs or even some metallic catalysts. 35301302 2 3 theme deposition 496:505 arg1 system 513:518 a chemical vapor deposition (CVD) system 479:518 a chemical vapor deposition (CVD) system 479:518 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 2 4 from conversion 465:474 arg1 system 513:518 a chemical vapor deposition (CVD) system 479:518 a chemical vapor deposition (CVD) system 479:518 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 2 5 theme large-area 362:371 arg1 -C=N- 373:377 large-area -C=N- 362:377 large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system 362:518 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 5 6 theme COF 987:989 arg1 films 991:995 PyTTA-TPA COF films 977:995 PyTTA-TPA COF films 977:995 The carrier mobility of PyTTA-TPA COF films can reach 1.89 × 10-3 cm2 V-1 s-1. 35301302 3 7 theme growth 693:698 arg1 substrate 700:708 growth substrate 693:708 growth substrate 693:708 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 1 8 from films 318:322 arg1 surface 336:342 solution surface 327:342 solution surface 327:342 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 7 9 from construction 1256:1267 arg1 substrates 1307:1316 substrates 1307:1316 substrates towards multi-functional applications of 2D π-conjugated systems 1307:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 3 10 theme Schiff 568:573 arg1 polycondensation 580:595 reversible Schiff base polycondensation 557:595 reversible Schiff base polycondensation 557:595 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 1 11 theme specific 166:173 arg1 area 183:186 high specific surface area 161:186 high specific surface area 161:186 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 4 12 with films 812:816 arg1 structures 833:842 different structures 823:842 different structures 823:842 Wafer-scale 2D COF films with different structures have been successfully synthesized by adjusting their building blocks, suggesting its generic applicability. 35301302 3 13 dep the 759:761 arg1 aid 763:765 aid 763:765 aid 763:765 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 7 14 theme large-area 1272:1281 arg1 films 1298:1302 large-area uniform 2D COF films 1272:1302 large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems 1272:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 4 15 theme different 823:831 arg1 structures 833:842 different structures 823:842 different structures 823:842 Wafer-scale 2D COF films with different structures have been successfully synthesized by adjusting their building blocks, suggesting its generic applicability. 35301302 2 16 dep two-dimensional 386:400 arg1 2D 403:404 2D 403:404 2D 403:404 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 1 17 theme surface 175:181 arg1 area 183:186 high specific surface area 161:186 high specific surface area 161:186 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 5 18 theme carrier 957:963 arg1 mobility 965:972 The carrier mobility 953:972 The carrier mobility of PyTTA-TPA COF films 953:995 The carrier mobility of PyTTA-TPA COF films can reach 1.89 × 10-3 cm2 V-1 s-1. 35301302 2 19 theme induced 457:463 arg1 conversion 465:474 vapor induced conversion 451:474 vapor induced conversion in a chemical vapor deposition (CVD) system 451:518 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 6 20 theme evolution 1071:1079 arg1 reaction 1081:1088 hydrogen evolution reaction 1062:1088 hydrogen evolution reaction (HER) 1062:1094 When employed as catalysts in hydrogen evolution reaction (HER), they show high electrocatalytic activity compared with metal-free COFs or even some metallic catalysts. 35301302 0 21 theme covalent 16:23 arg1 films 43:47 Two-dimensional covalent organic framework films 0:47 Two-dimensional covalent organic framework films prepared on various substrates through vapor 0:92 Two-dimensional covalent organic framework films prepared on various substrates through vapor induced conversion. 35301302 3 22 theme stacking 732:739 arg1 interactions 741:752 π-π stacking interactions 728:752 π-π stacking interactions with the aid of water and acetic acid 728:790 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 3 23 theme base 575:578 arg1 polycondensation 580:595 reversible Schiff base polycondensation 557:595 reversible Schiff base polycondensation 557:595 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 6 24 theme hydrogen 1062:1069 arg1 reaction 1081:1088 hydrogen evolution reaction 1062:1088 hydrogen evolution reaction (HER) 1062:1094 When employed as catalysts in hydrogen evolution reaction (HER), they show high electrocatalytic activity compared with metal-free COFs or even some metallic catalysts. 35301302 0 25 theme Two-dimensional 0:14 arg1 films 43:47 Two-dimensional covalent organic framework films 0:47 Two-dimensional covalent organic framework films prepared on various substrates through vapor 0:92 Two-dimensional covalent organic framework films prepared on various substrates through vapor induced conversion. 35301302 1 26 theme infusible 289:297 arg1 powders 299:305 insoluble and infusible powders 275:305 insoluble and infusible powders 275:305 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 1 27 from powders 299:305 arg1 surface 336:342 solution surface 327:342 solution surface 327:342 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 3 28 with interactions 741:752 arg1 the 759:761 the 759:761 the 759:761 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 1 29 theme catalytic 192:200 arg1 activity 202:209 catalytic activity 192:209 catalytic activity 192:209 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 0 30 theme framework 33:41 arg1 films 43:47 Two-dimensional covalent organic framework films 0:47 Two-dimensional covalent organic framework films prepared on various substrates through vapor 0:92 Two-dimensional covalent organic framework films prepared on various substrates through vapor induced conversion. 35301302 6 31 from catalysts 1049:1057 arg1 reaction 1081:1088 hydrogen evolution reaction 1062:1088 hydrogen evolution reaction (HER) 1062:1094 When employed as catalysts in hydrogen evolution reaction (HER), they show high electrocatalytic activity compared with metal-free COFs or even some metallic catalysts. 35301302 4 32 theme COF 808:810 arg1 films 812:816 Wafer-scale 2D COF films 793:816 Wafer-scale 2D COF films with different structures 793:842 Wafer-scale 2D COF films with different structures have been successfully synthesized by adjusting their building blocks, suggesting its generic applicability. 35301302 1 33 theme Covalent 114:121 arg1 COFs 143:146 COFs 143:146 COFs 143:146 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 1 33 theme Covalent 114:121 arg1 frameworks 131:140 Covalent organic frameworks 114:140 Covalent organic frameworks (COFs) 114:147 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 5 34 theme cm2 1019:1021 arg1 s-1 1027:1029 1.89 × 10-3 cm2 V-1 s-1 1007:1029 1.89 × 10-3 cm2 V-1 s-1 1007:1029 The carrier mobility of PyTTA-TPA COF films can reach 1.89 × 10-3 cm2 V-1 s-1. 35301302 7 35 theme films 1298:1302 arg1 construction 1256:1267 the direct construction 1245:1267 the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems 1245:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 0 36 theme organic 25:31 arg1 films 43:47 Two-dimensional covalent organic framework films 0:47 Two-dimensional covalent organic framework films prepared on various substrates through vapor 0:92 Two-dimensional covalent organic framework films prepared on various substrates through vapor induced conversion. 35301302 3 37 theme π-π 728:730 arg1 interactions 741:752 π-π stacking interactions 728:752 π-π stacking interactions with the aid of water and acetic acid 728:790 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 5 38 theme PyTTA-TPA 977:985 arg1 films 991:995 PyTTA-TPA COF films 977:995 PyTTA-TPA COF films 977:995 The carrier mobility of PyTTA-TPA COF films can reach 1.89 × 10-3 cm2 V-1 s-1. 35301302 1 39 theme organic 123:129 arg1 COFs 143:146 COFs 143:146 COFs 143:146 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 1 39 theme organic 123:129 arg1 frameworks 131:140 Covalent organic frameworks 114:140 Covalent organic frameworks (COFs) 114:147 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 2 40 theme controllable 422:433 arg1 thicknesses 435:445 controllable thicknesses 422:445 controllable thicknesses 422:445 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 2 41 theme vapor 490:494 arg1 system 513:518 a chemical vapor deposition (CVD) system 479:518 a chemical vapor deposition (CVD) system 479:518 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 1 42 theme fragile 310:316 arg1 films 318:322 fragile films 310:322 fragile films 310:322 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 4 43 theme generic 930:936 arg1 applicability 938:950 its generic applicability 926:950 its generic applicability 926:950 Wafer-scale 2D COF films with different structures have been successfully synthesized by adjusting their building blocks, suggesting its generic applicability. 35301302 3 44 theme uniform 650:656 arg1 framework 666:674 a uniform organic framework 648:674 a uniform organic framework film directly on growth substrate 648:708 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 4 45 theme 2D 805:806 arg1 films 812:816 Wafer-scale 2D COF films 793:816 Wafer-scale 2D COF films with different structures 793:842 Wafer-scale 2D COF films with different structures have been successfully synthesized by adjusting their building blocks, suggesting its generic applicability. 35301302 7 46 theme 2D 1291:1292 arg1 films 1298:1302 large-area uniform 2D COF films 1272:1302 large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems 1272:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 2 47 theme COF 407:409 arg1 films 411:415 two-dimensional (2D) COF films 386:415 two-dimensional (2D) COF films 386:415 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 2 48 theme chemical 481:488 arg1 system 513:518 a chemical vapor deposition (CVD) system 479:518 a chemical vapor deposition (CVD) system 479:518 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 7 49 theme multi-functional 1326:1341 arg1 applications 1343:1354 multi-functional applications 1326:1354 multi-functional applications of 2D π-conjugated systems 1326:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 2 50 dep films 411:415 arg1 thicknesses 435:445 controllable thicknesses 422:445 controllable thicknesses 422:445 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 1 51 theme traditional 216:226 arg1 methods 253:259 traditional solution-based synthesis methods 216:259 traditional solution-based synthesis methods 216:259 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 0 52 theme various 61:67 arg1 substrates 69:78 various substrates 61:78 various substrates 61:78 Two-dimensional covalent organic framework films prepared on various substrates through vapor induced conversion. 35301302 6 53 dep reaction 1081:1088 arg1 HER 1091:1093 HER 1091:1093 HER 1091:1093 When employed as catalysts in hydrogen evolution reaction (HER), they show high electrocatalytic activity compared with metal-free COFs or even some metallic catalysts. 35301302 2 54 theme CVD 508:510 arg1 system 513:518 a chemical vapor deposition (CVD) system 479:518 a chemical vapor deposition (CVD) system 479:518 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 7 55 from films 1298:1302 arg1 substrates 1307:1316 substrates 1307:1316 substrates towards multi-functional applications of 2D π-conjugated systems 1307:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 6 56 theme electrocatalytic 1112:1127 arg1 activity 1129:1136 high electrocatalytic activity 1107:1136 high electrocatalytic activity 1107:1136 When employed as catalysts in hydrogen evolution reaction (HER), they show high electrocatalytic activity compared with metal-free COFs or even some metallic catalysts. 35301302 1 57 theme solution 327:334 arg1 surface 336:342 solution surface 327:342 solution surface 327:342 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 3 58 theme film 676:679 arg1 framework 666:674 a uniform organic framework 648:674 a uniform organic framework film directly on growth substrate 648:708 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 3 59 theme PyTTA 605:609 arg1 film 611:614 PyTTA film 605:614 PyTTA film 605:614 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 7 60 theme 2D 1359:1360 arg1 systems 1375:1381 2D π-conjugated systems 1359:1381 2D π-conjugated systems 1359:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 6 61 theme high 1107:1110 arg1 activity 1129:1136 high electrocatalytic activity 1107:1136 high electrocatalytic activity 1107:1136 When employed as catalysts in hydrogen evolution reaction (HER), they show high electrocatalytic activity compared with metal-free COFs or even some metallic catalysts. 35301302 6 62 theme metallic 1181:1188 arg1 catalysts 1190:1198 even some metallic catalysts 1171:1198 even some metallic catalysts 1171:1198 When employed as catalysts in hydrogen evolution reaction (HER), they show high electrocatalytic activity compared with metal-free COFs or even some metallic catalysts. 35301302 5 63 theme V-1 1023:1025 arg1 s-1 1027:1029 1.89 × 10-3 cm2 V-1 s-1 1007:1029 1.89 × 10-3 cm2 V-1 s-1 1007:1029 The carrier mobility of PyTTA-TPA COF films can reach 1.89 × 10-3 cm2 V-1 s-1. 35301302 7 64 theme π-conjugated 1362:1373 arg1 systems 1375:1381 2D π-conjugated systems 1359:1381 2D π-conjugated systems 1359:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 5 65 theme films 991:995 arg1 mobility 965:972 The carrier mobility 953:972 The carrier mobility of PyTTA-TPA COF films 953:995 The carrier mobility of PyTTA-TPA COF films can reach 1.89 × 10-3 cm2 V-1 s-1. 35301302 4 66 theme Wafer-scale 793:803 arg1 films 812:816 Wafer-scale 2D COF films 793:816 Wafer-scale 2D COF films with different structures 793:842 Wafer-scale 2D COF films with different structures have been successfully synthesized by adjusting their building blocks, suggesting its generic applicability. 35301302 3 67 theme reversible 557:566 arg1 polycondensation 580:595 reversible Schiff base polycondensation 557:595 reversible Schiff base polycondensation 557:595 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 1 68 theme solution-based 228:241 arg1 methods 253:259 traditional solution-based synthesis methods 216:259 traditional solution-based synthesis methods 216:259 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 4 69 theme building 898:905 arg1 blocks 907:912 their building blocks 892:912 their building blocks 892:912 Wafer-scale 2D COF films with different structures have been successfully synthesized by adjusting their building blocks, suggesting its generic applicability. 35301302 3 70 theme organic 658:664 arg1 framework 666:674 a uniform organic framework 648:674 a uniform organic framework film directly on growth substrate 648:708 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 7 71 theme systems 1375:1381 arg1 applications 1343:1354 multi-functional applications 1326:1354 multi-functional applications of 2D π-conjugated systems 1326:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 7 72 from substrates 1307:1316 arg1 construction 1256:1267 the direct construction 1245:1267 the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems 1245:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 7 73 theme direct 1249:1254 arg1 construction 1256:1267 the direct construction 1245:1267 the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems 1245:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 1 74 theme synthesis 243:251 arg1 methods 253:259 traditional solution-based synthesis methods 216:259 traditional solution-based synthesis methods 216:259 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 7 75 theme COF 1294:1296 arg1 films 1298:1302 large-area uniform 2D COF films 1272:1302 large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems 1272:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 3 76 theme TPA 620:622 arg1 vapor 624:628 TPA vapor 620:628 TPA vapor 620:628 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 2 77 theme two-dimensional 386:400 arg1 films 411:415 two-dimensional (2D) COF films 386:415 two-dimensional (2D) COF films 386:415 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 7 78 theme versatile 1225:1233 arg1 route 1235:1239 a versatile route 1223:1239 a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems 1223:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 1 79 theme insoluble 275:283 arg1 powders 299:305 insoluble and infusible powders 275:305 insoluble and infusible powders 275:305 Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. 35301302 2 80 attach linked 379:384 arg3 conversion 465:474 vapor induced conversion 451:474 vapor induced conversion in a chemical vapor deposition (CVD) system 451:518 Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. 35301302 5 81 theme 1.89 × 10-3 1007:1017 arg1 s-1 1027:1029 1.89 × 10-3 cm2 V-1 s-1 1007:1029 1.89 × 10-3 cm2 V-1 s-1 1007:1029 The carrier mobility of PyTTA-TPA COF films can reach 1.89 × 10-3 cm2 V-1 s-1. 35301302 3 82 theme assembly 525:532 arg1 process 534:540 The assembly process 521:540 The assembly process 521:540 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35301302 7 83 theme uniform 1283:1289 arg1 films 1298:1302 large-area uniform 2D COF films 1272:1302 large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems 1272:1381 Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems. 35301302 3 84 theme acetic 780:785 arg1 acid 787:790 acetic acid 780:790 acetic acid 780:790 The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. 35079754 5 0 link N-linked 1012:1019 arg1 G0-N 1028:1031 the N-linked glycan G0-N 1008:1031 the N-linked glycan G0-N 1008:1031 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 6 1 theme terminal 1336:1343 arg1 galactose 1345:1353 a terminal galactose 1334:1353 a terminal galactose attached to either the α-3 or α-6 branch 1334:1394 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 1 2 from cells 181:185 arg1 organisms 201:209 all living organisms 190:209 all living organisms 190:209 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 1 3 theme biological 238:247 arg1 processes 249:257 most biological processes 233:257 most biological processes 233:257 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 7 4 theme positional 1614:1623 arg1 isomers 1625:1631 positional isomers 1614:1631 positional isomers 1614:1631 Starting with just a few analytical standards, this fragment-based spectroscopy method allows us to develop a database which we can use to identify positional isomers. 35079754 2 5 theme positional 368:377 arg1 isomers 379:385 positional isomers 368:385 positional isomers 368:385 Of particular importance are positional isomers, for which analytical standards are difficult to obtain. 35079754 0 6 theme determinant 110:120 arg1 fragments 126:134 structurally determinant CID fragments 97:134 structurally determinant CID fragments 97:134 Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments. 35079754 7 7 theme analytical 1491:1500 arg1 standards 1502:1510 just a few analytical standards 1480:1510 just a few analytical standards 1480:1510 Starting with just a few analytical standards, this fragment-based spectroscopy method allows us to develop a database which we can use to identify positional isomers. 35079754 1 8 from surface 170:176 arg1 organisms 201:209 all living organisms 190:209 all living organisms 190:209 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 3 9 theme positional 613:622 arg1 isomers 624:630 N-glycan positional isomers 604:630 N-glycan positional isomers 604:630 We combine ultrahigh-resolution ion-mobility spectrometry with collision-induced dissociation and cryogenic infrared spectroscopy to determine the structure of N-glycan positional isomers. 35079754 8 10 theme approach 1661:1668 arg1 generalization 1638:1651 The generalization 1634:1651 The generalization of this approach 1634:1668 The generalization of this approach would greatly facilitate glycan analysis. 35079754 5 11 theme N-glycan 1141:1148 arg1 core 1166:1169 the common N-glycan pentasaccharide core 1130:1169 the common N-glycan pentasaccharide core 1130:1169 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 3 12 theme isomers 624:630 arg1 structure 591:599 the structure 587:599 the structure of N-glycan positional isomers 587:630 We combine ultrahigh-resolution ion-mobility spectrometry with collision-induced dissociation and cryogenic infrared spectroscopy to determine the structure of N-glycan positional isomers. 35079754 6 13 theme identified 1215:1224 arg1 isomers 1226:1232 these newly identified isomers 1203:1232 these newly identified isomers 1203:1232 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 0 14 theme fragments 126:134 arg1 fingerprinting 79:92 vibrational fingerprinting 67:92 vibrational fingerprinting 67:92 Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments. 35079754 0 14 theme fragments 126:134 arg1 IMS 59:61 IMS 59:61 IMS 59:61 Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments. 35079754 1 15 located present 155:161 arg2 glycans 143:149 glycans 143:149 glycans 143:149 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 1 15 located present 155:161 arg1 surface 170:176 the surface 166:176 the surface of cells in all living organisms 166:209 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 6 16 theme complex-type 1306:1317 arg1 G1F 1279:1281 G1F 1279:1281 G1F 1279:1281 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 16 theme complex-type 1306:1317 arg1 G1 1272:1273 G1 1272:1273 G1 1272:1273 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 16 theme complex-type 1306:1317 arg1 N-glycans 1319:1327 biantennary complex-type N-glycans 1294:1327 biantennary complex-type N-glycans 1294:1327 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 17 theme isomers 1226:1232 arg1 fingerprints 1187:1198 IR fingerprints 1184:1198 IR fingerprints of these newly identified isomers 1184:1232 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 8 18 theme glycan 1695:1700 arg1 analysis 1702:1709 glycan analysis 1695:1709 glycan analysis 1695:1709 The generalization of this approach would greatly facilitate glycan analysis. 35079754 3 19 theme ultrahigh-resolution 455:474 arg1 spectrometry 489:500 ultrahigh-resolution ion-mobility spectrometry 455:500 ultrahigh-resolution ion-mobility spectrometry 455:500 We combine ultrahigh-resolution ion-mobility spectrometry with collision-induced dissociation and cryogenic infrared spectroscopy to determine the structure of N-glycan positional isomers. 35079754 0 20 theme CID 122:124 arg1 fragments 126:134 structurally determinant CID fragments 97:134 structurally determinant CID fragments 97:134 Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments. 35079754 5 21 theme core 1166:1169 arg1 α-3 1109:1111 the α-3 1105:1111 the α-3 1105:1111 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 5 21 theme core 1166:1169 arg1 branch 1120:1125 α-6 branch 1116:1125 α-6 branch of the common N-glycan pentasaccharide core 1116:1169 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 6 22 theme biantennary 1294:1304 arg1 G1F 1279:1281 G1F 1279:1281 G1F 1279:1281 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 22 theme biantennary 1294:1304 arg1 G1 1272:1273 G1 1272:1273 G1 1272:1273 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 22 theme biantennary 1294:1304 arg1 N-glycans 1319:1327 biantennary complex-type N-glycans 1294:1327 biantennary complex-type N-glycans 1294:1327 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 3 23 theme N-glycan 604:611 arg1 isomers 624:630 N-glycan positional isomers 604:630 N-glycan positional isomers 604:630 We combine ultrahigh-resolution ion-mobility spectrometry with collision-induced dissociation and cryogenic infrared spectroscopy to determine the structure of N-glycan positional isomers. 35079754 5 24 theme pentasaccharide 1150:1164 arg1 core 1166:1169 the common N-glycan pentasaccharide core 1130:1169 the common N-glycan pentasaccharide core 1130:1169 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 1 25 theme cells 181:185 arg1 surface 170:176 the surface 166:176 the surface of cells in all living organisms 166:209 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 4 26 theme diagnostic 726:735 arg1 fragments 737:745 diagnostic fragments 726:745 diagnostic fragments specific to each positional isomer 726:780 This approach is based on first separating the parent molecules by SLIM-based IMS, producing diagnostic fragments specific to each positional isomer, separating the fragments by IMS, and identifying them by comparing their IR fingerprints to a previously recorded spectral database. 35079754 5 27 theme N-linked 1012:1019 arg1 G0-N 1028:1031 the N-linked glycan G0-N 1008:1031 the N-linked glycan G0-N 1008:1031 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 1 28 attach present 155:161 arg1 surface 170:176 the surface 166:176 the surface of cells in all living organisms 166:209 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 1 28 attach present 155:161 arg2 glycans 143:149 glycans 143:149 glycans 143:149 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 2 29 theme analytical 398:407 arg1 standards 409:417 analytical standards 398:417 analytical standards 398:417 Of particular importance are positional isomers, for which analytical standards are difficult to obtain. 35079754 1 30 theme isomeric 266:273 arg1 complexity 275:284 their isomeric complexity 260:284 their isomeric complexity 260:284 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 7 31 theme fragment-based 1518:1531 arg1 method 1546:1551 this fragment-based spectroscopy method 1513:1551 this fragment-based spectroscopy method 1513:1551 Starting with just a few analytical standards, this fragment-based spectroscopy method allows us to develop a database which we can use to identify positional isomers. 35079754 5 32 theme glycan 1021:1026 arg1 G0-N 1028:1031 the N-linked glycan G0-N 1008:1031 the N-linked glycan G0-N 1008:1031 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 4 33 theme specific 747:754 arg1 fragments 737:745 diagnostic fragments 726:745 diagnostic fragments specific to each positional isomer 726:780 This approach is based on first separating the parent molecules by SLIM-based IMS, producing diagnostic fragments specific to each positional isomer, separating the fragments by IMS, and identifying them by comparing their IR fingerprints to a previously recorded spectral database. 35079754 0 34 theme positional 27:36 arg1 isomers 38:44 N-glycan positional isomers 18:44 N-glycan positional isomers 18:44 Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments. 35079754 6 35 theme G1 1272:1273 arg1 isomers 1261:1267 the positional isomers 1246:1267 the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc 1246:1463 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 5 36 theme G0-N 1028:1031 arg1 isomers 997:1003 the positional isomers 982:1003 the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core 982:1169 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 1 37 theme living 194:199 arg1 organisms 201:209 all living organisms 190:209 all living organisms 190:209 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 0 38 theme N-glycan 18:25 arg1 isomers 38:44 N-glycan positional isomers 18:44 N-glycan positional isomers 18:44 Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments. 35079754 4 39 theme SLIM-based 700:709 arg1 IMS 711:713 SLIM-based IMS 700:713 SLIM-based IMS 700:713 This approach is based on first separating the parent molecules by SLIM-based IMS, producing diagnostic fragments specific to each positional isomer, separating the fragments by IMS, and identifying them by comparing their IR fingerprints to a previously recorded spectral database. 35079754 6 40 theme G1F 1416:1418 arg1 a 1420:1420 G1F a 1416:1420 G1F a fucose attached to the reducing-end GlcNAc 1416:1463 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 4 41 theme recorded 888:895 arg1 database 906:913 a previously recorded spectral database 875:913 a previously recorded spectral database 875:913 This approach is based on first separating the parent molecules by SLIM-based IMS, producing diagnostic fragments specific to each positional isomer, separating the fragments by IMS, and identifying them by comparing their IR fingerprints to a previously recorded spectral database. 35079754 5 42 theme bottom-up 953:961 arg1 scheme 963:968 a bottom-up scheme 951:968 a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core 951:1169 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 0 43 theme isomers 38:44 arg1 Identification 0:13 Identification 0:13 Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments. 0:135 Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments. 35079754 1 44 theme structural 298:307 arg1 characterization 309:324 their structural characterization 292:324 their structural characterization 292:324 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 6 45 attach attached 1355:1362 arg2 galactose 1345:1353 a terminal galactose 1334:1353 a terminal galactose attached to either the α-3 or α-6 branch 1334:1394 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 45 attach attached 1355:1362 arg1 branch 1389:1394 α-6 branch 1385:1394 α-6 branch 1385:1394 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 45 attach attached 1355:1362 arg1 α-3 1378:1380 the α-3 1374:1380 the α-3 1374:1380 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 46 attach attached 1429:1436 arg2 a 1420:1420 G1F a 1416:1420 G1F a fucose attached to the reducing-end GlcNAc 1416:1463 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 46 attach attached 1429:1436 arg1 GlcNAc 1458:1463 the reducing-end GlcNAc 1441:1463 the reducing-end GlcNAc 1441:1463 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 5 47 theme common 1134:1139 arg1 core 1166:1169 the common N-glycan pentasaccharide core 1130:1169 the common N-glycan pentasaccharide core 1130:1169 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 3 48 theme infrared 552:559 arg1 spectroscopy 561:572 cryogenic infrared spectroscopy 542:572 cryogenic infrared spectroscopy 542:572 We combine ultrahigh-resolution ion-mobility spectrometry with collision-induced dissociation and cryogenic infrared spectroscopy to determine the structure of N-glycan positional isomers. 35079754 6 49 theme a 1420:1420 arg1 case 1408:1411 the case 1404:1411 the case of G1F a fucose attached to the reducing-end GlcNAc 1404:1463 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 50 theme G1F 1279:1281 arg1 isomers 1261:1267 the positional isomers 1246:1267 the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc 1246:1463 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 5 51 attach attached 1086:1093 arg2 N-acetylglucosamine 1054:1072 a terminal N-acetylglucosamine 1043:1072 a terminal N-acetylglucosamine (GlcNAc) 1043:1081 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 5 51 attach attached 1086:1093 arg3 G0-N 1028:1031 the N-linked glycan G0-N 1008:1031 the N-linked glycan G0-N 1008:1031 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 5 51 attach attached 1086:1093 arg1 α-3 1109:1111 the α-3 1105:1111 the α-3 1105:1111 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 5 51 attach attached 1086:1093 arg1 branch 1120:1125 α-6 branch 1116:1125 α-6 branch of the common N-glycan pentasaccharide core 1116:1169 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 5 51 attach attached 1086:1093 arg2 GlcNAc 1075:1080 GlcNAc 1075:1080 GlcNAc 1075:1080 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 7 52 theme spectroscopy 1533:1544 arg1 method 1546:1551 this fragment-based spectroscopy method 1513:1551 this fragment-based spectroscopy method 1513:1551 Starting with just a few analytical standards, this fragment-based spectroscopy method allows us to develop a database which we can use to identify positional isomers. 35079754 4 53 theme spectral 897:904 arg1 database 906:913 a previously recorded spectral database 875:913 a previously recorded spectral database 875:913 This approach is based on first separating the parent molecules by SLIM-based IMS, producing diagnostic fragments specific to each positional isomer, separating the fragments by IMS, and identifying them by comparing their IR fingerprints to a previously recorded spectral database. 35079754 2 54 theme importance 353:362 arg1 isomers 379:385 positional isomers 368:385 positional isomers 368:385 Of particular importance are positional isomers, for which analytical standards are difficult to obtain. 35079754 1 55 from organisms 201:209 arg1 surface 170:176 the surface 166:176 the surface of cells in all living organisms 166:209 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 2 56 theme particular 342:351 arg1 importance 353:362 particular importance 342:362 particular importance 342:362 Of particular importance are positional isomers, for which analytical standards are difficult to obtain. 35079754 6 57 with N-glycans 1319:1327 arg1 galactose 1345:1353 a terminal galactose 1334:1353 a terminal galactose attached to either the α-3 or α-6 branch 1334:1394 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 1 58 theme key 220:222 arg1 roles 224:228 key roles 220:228 key roles 220:228 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 35079754 5 59 theme terminal 1045:1052 arg1 GlcNAc 1075:1080 GlcNAc 1075:1080 GlcNAc 1075:1080 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 5 59 theme terminal 1045:1052 arg1 N-acetylglucosamine 1054:1072 a terminal N-acetylglucosamine 1043:1072 a terminal N-acetylglucosamine (GlcNAc) 1043:1081 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 5 60 theme positional 986:995 arg1 isomers 997:1003 the positional isomers 982:1003 the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core 982:1169 We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. 35079754 4 61 theme IR 856:857 arg1 fingerprints 859:870 their IR fingerprints 850:870 their IR fingerprints 850:870 This approach is based on first separating the parent molecules by SLIM-based IMS, producing diagnostic fragments specific to each positional isomer, separating the fragments by IMS, and identifying them by comparing their IR fingerprints to a previously recorded spectral database. 35079754 3 62 theme cryogenic 542:550 arg1 spectroscopy 561:572 cryogenic infrared spectroscopy 542:572 cryogenic infrared spectroscopy 542:572 We combine ultrahigh-resolution ion-mobility spectrometry with collision-induced dissociation and cryogenic infrared spectroscopy to determine the structure of N-glycan positional isomers. 35079754 6 63 theme IR 1184:1185 arg1 fingerprints 1187:1198 IR fingerprints 1184:1198 IR fingerprints of these newly identified isomers 1184:1232 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 64 from N-glycans 1319:1327 arg1 case 1408:1411 the case 1404:1411 the case of G1F a fucose attached to the reducing-end GlcNAc 1404:1463 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 0 65 theme vibrational 67:77 arg1 fingerprinting 79:92 vibrational fingerprinting 67:92 vibrational fingerprinting 67:92 Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments. 35079754 6 66 theme reducing-end 1445:1456 arg1 GlcNAc 1458:1463 the reducing-end GlcNAc 1441:1463 the reducing-end GlcNAc 1441:1463 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 6 67 theme positional 1250:1259 arg1 isomers 1261:1267 the positional isomers 1246:1267 the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc 1246:1463 We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. 35079754 3 68 theme collision-induced 507:523 arg1 dissociation 525:536 collision-induced dissociation 507:536 collision-induced dissociation 507:536 We combine ultrahigh-resolution ion-mobility spectrometry with collision-induced dissociation and cryogenic infrared spectroscopy to determine the structure of N-glycan positional isomers. 35079754 4 69 theme positional 764:773 arg1 isomer 775:780 each positional isomer 759:780 each positional isomer 759:780 This approach is based on first separating the parent molecules by SLIM-based IMS, producing diagnostic fragments specific to each positional isomer, separating the fragments by IMS, and identifying them by comparing their IR fingerprints to a previously recorded spectral database. 35079754 3 70 theme ion-mobility 476:487 arg1 spectrometry 489:500 ultrahigh-resolution ion-mobility spectrometry 455:500 ultrahigh-resolution ion-mobility spectrometry 455:500 We combine ultrahigh-resolution ion-mobility spectrometry with collision-induced dissociation and cryogenic infrared spectroscopy to determine the structure of N-glycan positional isomers. 35079754 4 71 theme parent 680:685 arg1 molecules 687:695 the parent molecules 676:695 the parent molecules by SLIM-based IMS 676:713 This approach is based on first separating the parent molecules by SLIM-based IMS, producing diagnostic fragments specific to each positional isomer, separating the fragments by IMS, and identifying them by comparing their IR fingerprints to a previously recorded spectral database. 35079754 1 72 theme most 233:236 arg1 processes 249:257 most biological processes 233:257 most biological processes 233:257 While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. 36982766 4 0 theme vein 914:917 arg1 ECs 938:940 ECs 938:940 ECs 938:940 The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). 36982766 4 0 theme vein 914:917 arg1 cells 931:935 human umbilical vein endothelial cells 898:935 human umbilical vein endothelial cells (ECs) 898:941 The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). 36982766 0 1 from Cells 21:25 arg1 Gel 50:52 Reinforced Collagen Gel 30:52 Reinforced Collagen Gel 30:52 Adipose-Derived Stem Cells in Reinforced Collagen Gel: A Comparison between Two Approaches to Differentiation towards Smooth Muscle Cells. 36982766 9 2 theme only 1532:1535 arg1 PVA_PL_part 1537:1547 only PVA_PL_part 1532:1547 only PVA_PL_part 1532:1547 Both PVA_PL_part samples and TGF + BMP_part samples supported ASC growth and differentiation towards SMCs, but only PVA_PL_part supported homogeneous endothelialisation. 36982766 2 3 theme porcine 349:355 arg1 skin 357:360 porcine skin 349:360 porcine skin 349:360 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 5 4 theme Willebrand 1013:1022 arg1 factor 1024:1029 von Willebrand factor 1009:1029 von Willebrand factor 1009:1029 The immunofluorescence staining of alpha-actin and calponin, and von Willebrand factor, was performed. 36982766 4 5 theme umbilical 904:912 arg1 ECs 938:940 ECs 938:940 ECs 938:940 The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). 36982766 4 5 theme umbilical 904:912 arg1 cells 931:935 human umbilical vein endothelial cells 898:935 human umbilical vein endothelial cells (ECs) 898:941 The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). 36982766 5 6 theme alpha-actin 979:989 arg1 staining 967:974 The immunofluorescence staining 944:974 The immunofluorescence staining of alpha-actin and calponin 944:1002 The immunofluorescence staining of alpha-actin and calponin, and von Willebrand factor, was performed. 36982766 5 6 theme alpha-actin 979:989 arg1 factor 1024:1029 von Willebrand factor 1009:1029 von Willebrand factor 1009:1029 The immunofluorescence staining of alpha-actin and calponin, and von Willebrand factor, was performed. 36982766 1 7 theme degradable 157:166 arg1 polymers 168:175 degradable polymers 157:175 degradable polymers 157:175 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. 36982766 1 7 theme degradable 157:166 arg1 polyesters 196:205 polyesters 196:205 polyesters 196:205 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. 36982766 1 7 theme degradable 157:166 arg1 polysaccharides 210:224 polysaccharides 210:224 polysaccharides 210:224 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. 36982766 1 7 theme degradable 157:166 arg1 collagen 186:193 collagen 186:193 collagen 186:193 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. 36982766 3 8 theme PVA 779:781 arg1 PVA_PL_part 795:805 PVA_PL_part 795:805 PVA_PL_part 795:805 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 8 theme PVA 779:781 arg1 nanofibers 783:792 PVA nanofibers 779:792 PVA nanofibers (PVA_PL_part) 779:806 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 8 9 theme TGF 1401:1403 arg1 gel 1416:1418 endothelialised TGF + BMP_part gel 1385:1418 endothelialised TGF + BMP_part gel 1385:1418 Gels evinced limited planar shrinkage, but it was higher in endothelialised TGF + BMP_part gel. 36982766 3 10 attach released 765:772 arg1 PVA_PL_part 795:805 PVA_PL_part 795:805 PVA_PL_part 795:805 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 10 attach released 765:772 arg1 nanofibers 783:792 PVA nanofibers 779:792 PVA nanofibers (PVA_PL_part) 779:806 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 10 attach released 765:772 arg2 lysate 758:763 human platelet lysate 743:763 human platelet lysate released from PVA nanofibers (PVA_PL_part) 743:806 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 6 11 theme matrix 1112:1117 arg1 proteins 1125:1132 the extracellular matrix (ECM) proteins 1094:1132 the extracellular matrix (ECM) proteins 1094:1132 The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. 36982766 10 12 theme PVA_PL_part 1667:1677 arg1 gel 1679:1681 PVA_PL_part gel 1667:1681 PVA_PL_part gel 1667:1681 Young modulus of elasticity increased in all samples compared to day 0, and PVA_PL_part gel evinced a slightly higher ratio of elastic energy. 36982766 3 13 theme muscle 682:687 arg1 SMCs 696:699 SMCs 696:699 SMCs 696:699 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 13 theme muscle 682:687 arg1 cells 689:693 smooth muscle cells 675:693 smooth muscle cells (SMCs) 675:700 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 6 14 theme mass 1182:1185 arg1 spectrometry 1187:1198 mass spectrometry 1182:1198 mass spectrometry 1182:1198 The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. 36982766 6 15 theme extracellular 1098:1110 arg1 proteins 1125:1132 the extracellular matrix (ECM) proteins 1094:1132 the extracellular matrix (ECM) proteins 1094:1132 The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. 36982766 4 16 theme endothelial 919:929 arg1 ECs 938:940 ECs 938:940 ECs 938:940 The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). 36982766 4 16 theme endothelial 919:929 arg1 cells 931:935 human umbilical vein endothelial cells 898:935 human umbilical vein endothelial cells (ECs) 898:941 The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). 36982766 11 17 theme highest 1798:1804 arg1 potential 1806:1814 the highest potential 1794:1814 the highest potential to remodel into a functional vascular wall 1794:1857 The results suggest that PVA_PL_part collagen construct has the highest potential to remodel into a functional vascular wall. 36982766 2 18 attach isolated 335:342 arg1 skin 357:360 porcine skin 349:360 porcine skin 349:360 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 2 18 attach isolated 335:342 arg2 collagen 326:333 collagen 326:333 collagen isolated from porcine skin 326:360 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 11 19 theme vascular 1845:1852 arg1 wall 1854:1857 a functional vascular wall 1832:1857 a functional vascular wall 1832:1857 The results suggest that PVA_PL_part collagen construct has the highest potential to remodel into a functional vascular wall. 36982766 10 20 theme energy 1726:1731 arg1 ratio 1709:1713 a slightly higher ratio 1691:1713 a slightly higher ratio of elastic energy 1691:1731 Young modulus of elasticity increased in all samples compared to day 0, and PVA_PL_part gel evinced a slightly higher ratio of elastic energy. 36982766 7 21 theme gels 1251:1254 arg1 properties 1233:1242 Mechanical properties 1222:1242 Mechanical properties of the gels with ASCs 1222:1264 Mechanical properties of the gels with ASCs were measured via an unconfined compression test on day 5. 36982766 5 22 theme von 1009:1011 arg1 factor 1024:1029 von Willebrand factor 1009:1029 von Willebrand factor 1009:1029 The immunofluorescence staining of alpha-actin and calponin, and von Willebrand factor, was performed. 36982766 2 23 link tissue-derived 453:466 arg1 ASCs 480:483 ASCs 480:483 ASCs 480:483 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 2 23 link tissue-derived 453:466 arg1 cells 473:477 incorporated adipose tissue-derived stem cells 432:477 incorporated adipose tissue-derived stem cells (ASCs) 432:484 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 3 24 with medium 546:551 arg1 FS 564:565 FS 564:565 FS (DMEM_part) 564:577 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 24 with medium 546:551 arg1 % 559:559 2% 558:559 2% of FS (DMEM_part) 558:577 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 24 with medium 546:551 arg1 DMEM_part 568:576 DMEM_part 568:576 DMEM_part 568:576 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 0 25 theme Stem 16:19 arg1 Cells 21:25 Adipose-Derived Stem Cells 0:25 Adipose-Derived Stem Cells in Reinforced Collagen Gel 0:52 Adipose-Derived Stem Cells in Reinforced Collagen Gel: A Comparison between Two Approaches to Differentiation towards Smooth Muscle Cells. 36982766 3 26 theme smooth 675:680 arg1 SMCs 696:699 SMCs 696:699 SMCs 696:699 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 26 theme smooth 675:680 arg1 cells 689:693 smooth muscle cells 675:693 smooth muscle cells (SMCs) 675:700 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 7 27 with gels 1251:1254 arg1 ASCs 1261:1264 ASCs 1261:1264 ASCs 1261:1264 Mechanical properties of the gels with ASCs were measured via an unconfined compression test on day 5. 36982766 8 28 theme BMP_part 1407:1414 arg1 gel 1416:1418 endothelialised TGF + BMP_part gel 1385:1418 endothelialised TGF + BMP_part gel 1385:1418 Gels evinced limited planar shrinkage, but it was higher in endothelialised TGF + BMP_part gel. 36982766 7 29 theme Mechanical 1222:1231 arg1 properties 1233:1242 Mechanical properties 1222:1242 Mechanical properties of the gels with ASCs 1222:1264 Mechanical properties of the gels with ASCs were measured via an unconfined compression test on day 5. 36982766 0 30 theme Adipose-Derived 0:14 arg1 Cells 21:25 Adipose-Derived Stem Cells 0:25 Adipose-Derived Stem Cells in Reinforced Collagen Gel 0:52 Adipose-Derived Stem Cells in Reinforced Collagen Gel: A Comparison between Two Approaches to Differentiation towards Smooth Muscle Cells. 36982766 1 31 theme bioartificial 269:281 arg1 grafts 292:297 bioartificial vascular grafts 269:297 bioartificial vascular grafts 269:297 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. 36982766 3 32 dep TGF-β1 816:821 arg1 TGF 832:834 TGF 832:834 TGF 832:834 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 32 dep TGF-β1 816:821 arg1 BMP_part 838:845 BMP_part 838:845 BMP_part 838:845 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 6 33 theme cell 1072:1075 arg1 differentiation 1077:1091 cell differentiation 1072:1091 cell differentiation 1072:1091 The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. 36982766 7 34 theme compression 1298:1308 arg1 test 1310:1313 an unconfined compression test 1284:1313 an unconfined compression test on day 5 1284:1322 Mechanical properties of the gels with ASCs were measured via an unconfined compression test on day 5. 36982766 1 35 theme vascular 283:290 arg1 grafts 292:297 bioartificial vascular grafts 269:297 bioartificial vascular grafts 269:297 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. 36982766 0 36 theme Muscle 125:130 arg1 Cells 132:136 Smooth Muscle Cells 118:136 Smooth Muscle Cells 118:136 Adipose-Derived Stem Cells in Reinforced Collagen Gel: A Comparison between Two Approaches to Differentiation towards Smooth Muscle Cells. 36982766 11 37 contain has 1790:1792 arg1 construct 1780:1788 PVA_PL_part collagen construct 1759:1788 PVA_PL_part collagen construct 1759:1788 The results suggest that PVA_PL_part collagen construct has the highest potential to remodel into a functional vascular wall. 36982766 11 37 contain has 1790:1792 arg2 potential 1806:1814 the highest potential 1794:1814 the highest potential to remodel into a functional vascular wall 1794:1857 The results suggest that PVA_PL_part collagen construct has the highest potential to remodel into a functional vascular wall. 36982766 0 38 dep Comparison 57:66 arg1 Cells 21:25 Adipose-Derived Stem Cells 0:25 Adipose-Derived Stem Cells in Reinforced Collagen Gel 0:52 Adipose-Derived Stem Cells in Reinforced Collagen Gel: A Comparison between Two Approaches to Differentiation towards Smooth Muscle Cells. 36982766 6 39 theme remodelling 1143:1153 arg1 proteins 1155:1162 ECM remodelling proteins 1139:1162 ECM remodelling proteins 1139:1162 The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. 36982766 2 40 theme collagen 404:411 arg1 particles 413:421 collagen particles 404:421 collagen particles 404:421 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 9 41 theme BMP_part 1456:1463 arg1 samples 1465:1471 TGF + BMP_part samples 1450:1471 TGF + BMP_part samples 1450:1471 Both PVA_PL_part samples and TGF + BMP_part samples supported ASC growth and differentiation towards SMCs, but only PVA_PL_part supported homogeneous endothelialisation. 36982766 1 42 theme grafts 292:297 arg1 fabrication 254:264 fabrication 254:264 fabrication of bioartificial vascular grafts or patches 254:308 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. 36982766 0 43 theme Smooth 118:123 arg1 Cells 132:136 Smooth Muscle Cells 118:136 Smooth Muscle Cells 118:136 Adipose-Derived Stem Cells in Reinforced Collagen Gel: A Comparison between Two Approaches to Differentiation towards Smooth Muscle Cells. 36982766 5 44 theme calponin 995:1002 arg1 staining 967:974 The immunofluorescence staining 944:974 The immunofluorescence staining of alpha-actin and calponin 944:1002 The immunofluorescence staining of alpha-actin and calponin, and von Willebrand factor, was performed. 36982766 5 44 theme calponin 995:1002 arg1 factor 1024:1029 von Willebrand factor 1009:1029 von Willebrand factor 1009:1029 The immunofluorescence staining of alpha-actin and calponin, and von Willebrand factor, was performed. 36982766 3 45 theme cell-material 491:503 arg1 constructs 505:514 The cell-material constructs 487:514 The cell-material constructs 487:514 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 10 46 theme Young 1591:1595 arg1 modulus 1597:1603 Young modulus 1591:1603 Young modulus of elasticity 1591:1617 Young modulus of elasticity increased in all samples compared to day 0, and PVA_PL_part gel evinced a slightly higher ratio of elastic energy. 36982766 0 47 theme Collagen 41:48 arg1 Gel 50:52 Reinforced Collagen Gel 30:52 Reinforced Collagen Gel 30:52 Adipose-Derived Stem Cells in Reinforced Collagen Gel: A Comparison between Two Approaches to Differentiation towards Smooth Muscle Cells. 36982766 8 48 theme limited 1338:1344 arg1 shrinkage 1353:1361 limited planar shrinkage 1338:1361 limited planar shrinkage 1338:1361 Gels evinced limited planar shrinkage, but it was higher in endothelialised TGF + BMP_part gel. 36982766 3 49 theme FS 564:565 arg1 FS 564:565 FS 564:565 FS (DMEM_part) 564:577 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 49 theme FS 564:565 arg1 % 559:559 2% 558:559 2% of FS (DMEM_part) 558:577 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 49 theme FS 564:565 arg1 DMEM_part 568:576 DMEM_part 568:576 DMEM_part 568:576 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 0 50 theme Reinforced 30:39 arg1 Gel 50:52 Reinforced Collagen Gel 30:52 Reinforced Collagen Gel 30:52 Adipose-Derived Stem Cells in Reinforced Collagen Gel: A Comparison between Two Approaches to Differentiation towards Smooth Muscle Cells. 36982766 1 51 theme patches 302:308 arg1 fabrication 254:264 fabrication 254:264 fabrication of bioartificial vascular grafts or patches 254:308 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. 36982766 2 52 theme stem 468:471 arg1 ASCs 480:483 ASCs 480:483 ASCs 480:483 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 2 52 theme stem 468:471 arg1 cells 473:477 incorporated adipose tissue-derived stem cells 432:477 incorporated adipose tissue-derived stem cells (ASCs) 432:484 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 3 53 theme added 585:589 arg1 nanofibers 608:617 added polyvinylalcohol nanofibers 585:617 added polyvinylalcohol nanofibers (PVA_part sample) 585:635 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 53 theme added 585:589 arg1 sample 629:634 PVA_part sample 620:634 PVA_part sample 620:634 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 6 54 theme ECM 1139:1141 arg1 proteins 1155:1162 ECM remodelling proteins 1139:1162 ECM remodelling proteins 1139:1162 The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. 36982766 8 55 theme planar 1346:1351 arg1 shrinkage 1353:1361 limited planar shrinkage 1338:1361 limited planar shrinkage 1338:1361 Gels evinced limited planar shrinkage, but it was higher in endothelialised TGF + BMP_part gel. 36982766 2 56 theme tissue-derived 453:466 arg1 ASCs 480:483 ASCs 480:483 ASCs 480:483 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 2 56 theme tissue-derived 453:466 arg1 cells 473:477 incorporated adipose tissue-derived stem cells 432:477 incorporated adipose tissue-derived stem cells (ASCs) 432:484 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 3 57 theme polyvinylalcohol 591:606 arg1 nanofibers 608:617 added polyvinylalcohol nanofibers 585:617 added polyvinylalcohol nanofibers (PVA_part sample) 585:635 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 57 theme polyvinylalcohol 591:606 arg1 sample 629:634 PVA_part sample 620:634 PVA_part sample 620:634 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 10 58 theme higher 1702:1707 arg1 ratio 1709:1713 a slightly higher ratio 1691:1713 a slightly higher ratio of elastic energy 1691:1731 Young modulus of elasticity increased in all samples compared to day 0, and PVA_PL_part gel evinced a slightly higher ratio of elastic energy. 36982766 8 59 theme endothelialised 1385:1399 arg1 gel 1416:1418 endothelialised TGF + BMP_part gel 1385:1418 endothelialised TGF + BMP_part gel 1385:1418 Gels evinced limited planar shrinkage, but it was higher in endothelialised TGF + BMP_part gel. 36982766 2 60 theme adipose 445:451 arg1 ASCs 480:483 ASCs 480:483 ASCs 480:483 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 2 60 theme adipose 445:451 arg1 cells 473:477 incorporated adipose tissue-derived stem cells 432:477 incorporated adipose tissue-derived stem cells (ASCs) 432:484 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 6 61 theme culture 1213:1219 arg1 day 1203:1205 day 12 1203:1208 day 12 of culture 1203:1219 The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. 36982766 5 62 theme immunofluorescence 948:965 arg1 staining 967:974 The immunofluorescence staining 944:974 The immunofluorescence staining of alpha-actin and calponin 944:1002 The immunofluorescence staining of alpha-actin and calponin, and von Willebrand factor, was performed. 36982766 9 63 theme homogeneous 1559:1569 arg1 endothelialisation 1571:1588 homogeneous endothelialisation 1559:1588 homogeneous endothelialisation 1559:1588 Both PVA_PL_part samples and TGF + BMP_part samples supported ASC growth and differentiation towards SMCs, but only PVA_PL_part supported homogeneous endothelialisation. 36982766 11 64 theme PVA_PL_part 1759:1769 arg1 construct 1780:1788 PVA_PL_part collagen construct 1759:1788 PVA_PL_part collagen construct 1759:1788 The results suggest that PVA_PL_part collagen construct has the highest potential to remodel into a functional vascular wall. 36982766 11 65 theme collagen 1771:1778 arg1 construct 1780:1788 PVA_PL_part collagen construct 1759:1788 PVA_PL_part collagen construct 1759:1788 The results suggest that PVA_PL_part collagen construct has the highest potential to remodel into a functional vascular wall. 36982766 7 66 theme unconfined 1287:1296 arg1 test 1310:1313 an unconfined compression test 1284:1313 an unconfined compression test on day 5 1284:1322 Mechanical properties of the gels with ASCs were measured via an unconfined compression test on day 5. 36982766 10 67 theme elasticity 1608:1617 arg1 modulus 1597:1603 Young modulus 1591:1603 Young modulus of elasticity 1591:1617 Young modulus of elasticity increased in all samples compared to day 0, and PVA_PL_part gel evinced a slightly higher ratio of elastic energy. 36982766 3 68 theme DMEM 541:544 arg1 medium 546:551 a DMEM medium 539:551 a DMEM medium with 2% of FS (DMEM_part) 539:577 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 69 theme human 743:747 arg1 lysate 758:763 human platelet lysate 743:763 human platelet lysate released from PVA nanofibers (PVA_PL_part) 743:806 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 9 70 theme TGF 1450:1452 arg1 samples 1465:1471 TGF + BMP_part samples 1450:1471 TGF + BMP_part samples 1450:1471 Both PVA_PL_part samples and TGF + BMP_part samples supported ASC growth and differentiation towards SMCs, but only PVA_PL_part supported homogeneous endothelialisation. 36982766 3 71 theme PVA_part 620:627 arg1 nanofibers 608:617 added polyvinylalcohol nanofibers 585:617 added polyvinylalcohol nanofibers (PVA_part sample) 585:635 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 3 71 theme PVA_part 620:627 arg1 sample 629:634 PVA_part sample 620:634 PVA_part sample 620:634 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 9 72 theme PVA_PL_part 1426:1436 arg1 samples 1438:1444 PVA_PL_part samples 1426:1444 PVA_PL_part samples 1426:1444 Both PVA_PL_part samples and TGF + BMP_part samples supported ASC growth and differentiation towards SMCs, but only PVA_PL_part supported homogeneous endothelialisation. 36982766 3 73 theme platelet 749:756 arg1 lysate 758:763 human platelet lysate 743:763 human platelet lysate released from PVA nanofibers (PVA_PL_part) 743:806 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 4 74 theme human 898:902 arg1 ECs 938:940 ECs 938:940 ECs 938:940 The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). 36982766 4 74 theme human 898:902 arg1 cells 931:935 human umbilical vein endothelial cells 898:935 human umbilical vein endothelial cells (ECs) 898:941 The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). 36982766 6 75 theme ECM 1120:1122 arg1 proteins 1125:1132 the extracellular matrix (ECM) proteins 1094:1132 the extracellular matrix (ECM) proteins 1094:1132 The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. 36982766 11 76 theme functional 1834:1843 arg1 wall 1854:1857 a functional vascular wall 1832:1857 a functional vascular wall 1832:1857 The results suggest that PVA_PL_part collagen construct has the highest potential to remodel into a functional vascular wall. 36982766 7 77 from test 1310:1313 arg1 day 1318:1320 day 5 1318:1322 day 5 1318:1322 Mechanical properties of the gels with ASCs were measured via an unconfined compression test on day 5. 36982766 9 78 theme ASC 1483:1485 arg1 growth 1487:1492 ASC growth 1483:1492 ASC growth 1483:1492 Both PVA_PL_part samples and TGF + BMP_part samples supported ASC growth and differentiation towards SMCs, but only PVA_PL_part supported homogeneous endothelialisation. 36982766 3 79 theme ASCs 646:649 arg1 differentiation 651:665 ASCs differentiation 646:665 ASCs differentiation towards smooth muscle cells (SMCs) 646:700 The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). 36982766 10 80 theme elastic 1718:1724 arg1 energy 1726:1731 elastic energy 1718:1731 elastic energy 1718:1731 Young modulus of elasticity increased in all samples compared to day 0, and PVA_PL_part gel evinced a slightly higher ratio of elastic energy. 36982766 2 81 theme incorporated 432:443 arg1 ASCs 480:483 ASCs 480:483 ASCs 480:483 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 2 81 theme incorporated 432:443 arg1 cells 473:477 incorporated adipose tissue-derived stem cells 432:477 incorporated adipose tissue-derived stem cells (ASCs) 432:484 In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). 36982766 1 82 theme promising 231:239 arg1 Scaffolds 139:147 Scaffolds 139:147 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, 139:225 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. 36982766 1 82 theme promising 231:239 arg1 matrices 241:248 promising matrices 231:248 promising matrices for fabrication of bioartificial vascular grafts or patches 231:308 Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. 37398272 3 0 theme S 531:531 arg1 NISE 546:549 NISE 546:549 NISE 546:549 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 3 0 theme S 531:531 arg1 s 543:543 S ubstrat E s 531:543 S ubstrat E s (NISE) 531:550 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 1 1 theme organisms 262:270 arg1 lifespan 232:239 the lifespan 228:239 the lifespan of all multicellular organisms 228:270 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 6 2 theme systems-level 1164:1176 arg1 approach 1178:1185 this holistic and unbiased systems-level approach 1137:1185 approach 1178:1185 Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states. 37398272 3 3 theme ubstrat 533:539 arg1 NISE 546:549 NISE 546:549 NISE 546:549 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 3 3 theme ubstrat 533:539 arg1 s 543:543 S ubstrat E s 531:543 S ubstrat E s (NISE) 531:550 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 6 4 from roles 1268:1272 arg1 types 1291:1295 specific cell types 1277:1295 specific cell types 1277:1295 Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states. 37398272 6 4 from roles 1268:1272 arg1 states 1312:1317 biological states 1301:1317 biological states 1301:1317 Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states. 37398272 5 5 theme synaptic 1099:1106 arg1 morphology 1108:1117 synaptic morphology 1099:1117 synaptic morphology 1099:1117 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 6 6 theme biological 1301:1310 arg1 states 1312:1317 biological states 1301:1317 biological states 1301:1317 Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states. 37398272 6 7 theme diverse 1260:1266 arg1 roles 1268:1272 their diverse roles 1254:1272 their diverse roles in specific cell types and biological states 1254:1317 Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states. 37398272 4 8 theme network 782:788 arg1 generation 790:799 network generation 782:799 network generation 782:799 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 4 9 theme unsupervised 805:816 arg1 partitioning 818:829 unsupervised partitioning 805:829 unsupervised partitioning 805:829 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 2 10 theme functional 293:302 arg1 studies 304:310 nearly all functional studies 282:310 nearly all functional studies 282:310 However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. 37398272 2 11 theme protein 339:345 arg1 modifications 347:359 individual protein modifications 328:359 individual protein modifications 328:359 However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. 37398272 3 12 theme nteractors 516:525 arg1 s 543:543 S ubstrat E s 531:543 S ubstrat E s (NISE) 531:550 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 3 12 theme nteractors 516:525 arg1 NISE 546:549 NISE 546:549 NISE 546:549 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 3 12 theme nteractors 516:525 arg1 etworking 501:509 N etworking 499:509 N etworking of I nteractors 499:525 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 6 13 theme unbiased 1155:1162 arg1 approach 1178:1185 this holistic and unbiased systems-level approach 1137:1185 approach 1178:1185 Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states. 37398272 1 14 theme post-translational 80:97 arg1 widespread 190:199 widespread 190:199 widespread 190:199 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 1 14 theme post-translational 80:97 arg1 PTM 113:115 PTM 113:115 PTM 113:115 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 1 14 theme post-translational 80:97 arg1 modification 99:110 The post-translational modification 76:110 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) 76:185 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 4 15 theme purification-mass 692:708 arg1 AP-MS 724:728 AP-MS 724:728 AP-MS 724:728 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 4 15 theme purification-mass 692:708 arg1 spectrometry 710:721 affinity purification-mass spectrometry 683:721 affinity purification-mass spectrometry (AP-MS) 683:729 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 5 16 theme conserved 987:995 arg1 regulation 1046:1055 epigenetic regulation 1035:1055 epigenetic regulation as well as tissue-specific functions like synaptic morphology 1035:1117 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 5 16 theme conserved 987:995 arg1 activities 997:1006 both conserved activities 982:1006 both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology 982:1117 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 5 16 theme conserved 987:995 arg1 functions 1084:1092 tissue-specific functions 1068:1092 epigenetic regulation as well as tissue-specific functions like synaptic morphology 1035:1117 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 6 17 theme cell 1286:1289 arg1 types 1291:1295 specific cell types 1277:1295 specific cell types 1277:1295 Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states. 37398272 6 18 theme applicable 1206:1215 arg1 framework 1217:1225 a broadly applicable framework 1196:1225 a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states 1196:1317 Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states. 37398272 4 19 with spectrometry 710:721 arg1 generation 790:799 network generation 782:799 network generation 782:799 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 4 19 with spectrometry 710:721 arg1 partitioning 818:829 unsupervised partitioning 805:829 unsupervised partitioning 805:829 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 2 20 theme individual 328:337 arg1 modifications 347:359 individual protein modifications 328:359 individual protein modifications 328:359 However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. 37398272 2 21 theme events 420:425 arg1 multitude 378:386 the multitude 374:386 the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities 374:478 However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. 37398272 0 22 theme Functional 0:9 arg1 glycoproteomics 11:25 Functional glycoproteomics 0:25 Functional glycoproteomics by integrated network assembly and partitioning 0:73 Functional glycoproteomics by integrated network assembly and partitioning. 37398272 4 23 theme chemoproteomic 749:762 arg1 technologies 764:775 site-specific chemoproteomic technologies 735:775 site-specific chemoproteomic technologies with network generation and unsupervised partitioning 735:829 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 5 24 theme epigenetic 1035:1044 arg1 regulation 1046:1055 epigenetic regulation 1035:1055 epigenetic regulation as well as tissue-specific functions like synaptic morphology 1035:1117 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 6 25 theme specific 1277:1284 arg1 types 1291:1295 specific cell types 1277:1295 specific cell types 1277:1295 Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states. 37398272 2 26 theme O-GlcNAcylation 404:418 arg1 events 420:425 simultaneous O-GlcNAcylation events 391:425 simultaneous O-GlcNAcylation events that work together to coordinate cellular activities 391:478 However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. 37398272 0 27 theme integrated 30:39 arg1 assembly 49:56 integrated network assembly 30:56 integrated network assembly 30:56 Functional glycoproteomics by integrated network assembly and partitioning. 37398272 3 28 theme N 499:499 arg1 etworking 501:509 N etworking 499:509 N etworking of I nteractors 499:525 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 5 29 theme tissue-specific 1068:1082 arg1 functions 1084:1092 tissue-specific functions 1068:1092 epigenetic regulation as well as tissue-specific functions like synaptic morphology 1035:1117 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 3 30 theme novel 555:559 arg1 approach 576:583 a novel, systems-level approach 553:583 a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome 553:658 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 3 31 theme E 541:541 arg1 NISE 546:549 NISE 546:549 NISE 546:549 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 3 31 theme E 541:541 arg1 s 543:543 S ubstrat E s 531:543 S ubstrat E s (NISE) 531:550 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 4 32 theme affinity 683:690 arg1 AP-MS 724:728 AP-MS 724:728 AP-MS 724:728 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 4 32 theme affinity 683:690 arg1 spectrometry 710:721 affinity purification-mass spectrometry 683:721 affinity purification-mass spectrometry (AP-MS) 683:729 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 5 33 theme resulting 920:928 arg1 network 930:936 The resulting network 916:936 The resulting network 916:936 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 0 34 theme network 41:47 arg1 assembly 49:56 integrated network assembly 30:56 integrated network assembly 30:56 Functional glycoproteomics by integrated network assembly and partitioning. 37398272 5 35 theme data-rich 949:957 arg1 framework 959:967 a data-rich framework 947:967 a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology 947:1117 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 4 36 theme downstream 877:886 arg1 targets 888:894 downstream targets 877:894 downstream targets of O-GlcNAcylation 877:913 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 1 37 link O-linked 133:140 arg1 -acetyl-D-glucosamine 147:167 O-linked β- N -acetyl-D-glucosamine 133:167 O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) 133:185 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 1 37 link O-linked 133:140 arg1 O-GlcNAcylation 170:184 O-GlcNAcylation 170:184 O-GlcNAcylation 170:184 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 4 38 theme O-GlcNAcylation 899:913 arg1 targets 888:894 downstream targets 877:894 downstream targets of O-GlcNAcylation 877:913 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 1 39 theme proteins 121:128 arg1 widespread 190:199 widespread 190:199 widespread 190:199 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 1 39 theme proteins 121:128 arg1 PTM 113:115 PTM 113:115 PTM 113:115 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 1 39 theme proteins 121:128 arg1 modification 99:110 The post-translational modification 76:110 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) 76:185 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 4 40 theme site-specific 735:747 arg1 technologies 764:775 site-specific chemoproteomic technologies 735:775 site-specific chemoproteomic technologies with network generation and unsupervised partitioning 735:829 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 1 41 theme N 145:145 arg1 -acetyl-D-glucosamine 147:167 O-linked β- N -acetyl-D-glucosamine 133:167 O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) 133:185 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 1 41 theme N 145:145 arg1 O-GlcNAcylation 170:184 O-GlcNAcylation 170:184 O-GlcNAcylation 170:184 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 4 42 theme upstream 852:859 arg1 regulators 861:870 potential upstream regulators 842:870 potential upstream regulators 842:870 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 1 43 theme O-linked 133:140 arg1 -acetyl-D-glucosamine 147:167 O-linked β- N -acetyl-D-glucosamine 133:167 O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) 133:185 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 1 43 theme O-linked 133:140 arg1 O-GlcNAcylation 170:184 O-GlcNAcylation 170:184 O-GlcNAcylation 170:184 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 4 44 theme potential 842:850 arg1 regulators 861:870 potential upstream regulators 842:870 potential upstream regulators 842:870 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 1 45 theme β- 142:143 arg1 -acetyl-D-glucosamine 147:167 O-linked β- N -acetyl-D-glucosamine 133:167 O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) 133:185 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 1 45 theme β- 142:143 arg1 O-GlcNAcylation 170:184 O-GlcNAcylation 170:184 O-GlcNAcylation 170:184 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 37398272 5 46 theme O-GlcNAcylation 1011:1025 arg1 regulation 1046:1055 epigenetic regulation 1035:1055 epigenetic regulation as well as tissue-specific functions like synaptic morphology 1035:1117 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 5 46 theme O-GlcNAcylation 1011:1025 arg1 activities 997:1006 both conserved activities 982:1006 both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology 982:1117 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 5 46 theme O-GlcNAcylation 1011:1025 arg1 functions 1084:1092 tissue-specific functions 1068:1092 epigenetic regulation as well as tissue-specific functions like synaptic morphology 1035:1117 The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. 37398272 2 47 theme cellular 460:467 arg1 activities 469:478 cellular activities 460:478 cellular activities 460:478 However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. 37398272 2 48 theme simultaneous 391:402 arg1 events 420:425 simultaneous O-GlcNAcylation events 391:425 simultaneous O-GlcNAcylation events that work together to coordinate cellular activities 391:478 However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. 37398272 3 49 theme I 514:514 arg1 nteractors 516:525 I nteractors 514:525 I nteractors 514:525 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 4 50 with technologies 764:775 arg1 generation 790:799 network generation 782:799 network generation 782:799 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 4 50 with technologies 764:775 arg1 partitioning 818:829 unsupervised partitioning 805:829 unsupervised partitioning 805:829 Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. 37398272 3 51 dep novel 555:559 arg1 systems-level 562:574 systems-level 562:574 systems-level 562:574 Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. 37398272 1 52 theme multicellular 248:260 arg1 organisms 262:270 all multicellular organisms 244:270 all multicellular organisms 244:270 The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. 36242043 11 0 from SCWs 1852:1855 arg1 crops 1870:1874 bioenergy crops 1860:1874 bioenergy crops 1860:1874 Therefore, the study of the function of CEF3 can provide a strategy for genetic modification of SCWs in bioenergy crops. 36242043 10 1 from saccharification 1723:1738 arg1 plants 1748:1753 rice plants 1743:1753 rice plants 1743:1753 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 2 2 theme Membrane 321:328 arg1 trafficking 330:340 Membrane trafficking 321:340 Membrane trafficking 321:340 Membrane trafficking plays key roles in SCWs biosynthesis, but information association membrane trafficking and SCWs formation in plants is limited. 36242043 10 3 theme secondary 1613:1621 arg1 wall 1628:1631 the secondary cell wall 1609:1631 the secondary cell wall 1609:1631 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 1 4 contain contain 276:282 arg2 walls 307:311 secondary cell walls 292:311 secondary cell walls (SCWs) 292:318 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 1 4 contain contain 276:282 arg1 residues 262:269 agronomic biomass residues 244:269 agronomic biomass residues that contain lots of secondary cell walls (SCWs) 244:318 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 1 4 contain contain 276:282 arg2 lots 284:287 lots 284:287 lots of secondary cell walls (SCWs) 284:318 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 1 4 contain contain 276:282 arg2 SCWs 314:317 SCWs 314:317 SCWs 314:317 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 3 5 with retardation 602:612 arg1 thickness 717:725 reduced secondary wall thickness 694:725 reduced secondary wall thickness 694:725 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 3 5 with retardation 602:612 arg1 composition 678:688 significantly altered cell wall composition 646:688 significantly altered cell wall composition 646:688 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 1 6 theme biomass 254:260 arg1 residues 262:269 agronomic biomass residues 244:269 agronomic biomass residues that contain lots of secondary cell walls (SCWs) 244:318 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 4 7 theme CYTOKINESIS 818:828 arg1 DEFECTIVE2 830:839 Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 797:839 Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2) 797:846 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 4 7 theme CYTOKINESIS 818:828 arg1 SCD2 842:845 SCD2 842:845 SCD2 842:845 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 3 8 theme cell 668:671 arg1 composition 678:688 significantly altered cell wall composition 646:688 significantly altered cell wall composition 646:688 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 11 9 from modification 1836:1847 arg1 crops 1870:1874 bioenergy crops 1860:1874 bioenergy crops 1860:1874 Therefore, the study of the function of CEF3 can provide a strategy for genetic modification of SCWs in bioenergy crops. 36242043 1 10 theme residues 262:269 arg1 large 235:239 large 235:239 large 235:239 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 3 11 theme wall 712:715 arg1 thickness 717:725 reduced secondary wall thickness 694:725 reduced secondary wall thickness 694:725 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 9 12 theme CEF3 1242:1245 arg1 mutation 1230:1237 mutation 1230:1237 mutation of CEF3 1230:1245 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 3 13 theme mutant 543:548 arg1 characterization 516:531 the function characterization 503:531 the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness 503:725 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 10 14 theme wall 1628:1631 arg1 biosynthesis 1593:1604 normal cellulose and other polysaccharides biosynthesis 1550:1604 normal cellulose and other polysaccharides biosynthesis of the secondary cell wall 1550:1631 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 3 15 theme reduced 694:700 arg1 thickness 717:725 reduced secondary wall thickness 694:725 reduced secondary wall thickness 694:725 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 1 16 theme important 192:200 arg1 crops 214:218 the most important staple food crops 183:218 the most important staple food crops 183:218 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 6 17 theme Expression 953:962 arg1 analysis 972:979 Expression pattern analysis 953:979 Expression pattern analysis 953:979 Expression pattern analysis indicated that CEF3 is ubiquitously expressed in many organs at different developmental stages. 36242043 11 18 theme bioenergy 1860:1868 arg1 crops 1870:1874 bioenergy crops 1860:1874 bioenergy crops 1860:1874 Therefore, the study of the function of CEF3 can provide a strategy for genetic modification of SCWs in bioenergy crops. 36242043 0 19 theme enzymatic 126:134 arg1 saccharification 136:151 biomass enzymatic saccharification 118:151 biomass enzymatic saccharification 118:151 CEF3 is involved in membrane trafficking and essential for secondary cell wall biosynthesis and its mutation enhanced biomass enzymatic saccharification in rice. 36242043 9 20 theme cellulose 1265:1273 arg1 expression 1299:1308 cellulose synthesis-related genes expression 1265:1308 cellulose synthesis-related genes expression 1265:1308 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 1 21 theme food 209:212 arg1 crops 214:218 the most important staple food crops 183:218 the most important staple food crops 183:218 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 11 22 theme SCWs 1852:1855 arg1 modification 1836:1847 genetic modification 1828:1847 genetic modification of SCWs in bioenergy crops 1828:1874 Therefore, the study of the function of CEF3 can provide a strategy for genetic modification of SCWs in bioenergy crops. 36242043 9 23 theme genes 1293:1297 arg1 expression 1299:1308 cellulose synthesis-related genes expression 1265:1308 cellulose synthesis-related genes expression 1265:1308 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 6 24 theme many 1030:1033 arg1 organs 1035:1040 many organs 1030:1040 many organs 1030:1040 Expression pattern analysis indicated that CEF3 is ubiquitously expressed in many organs at different developmental stages. 36242043 0 25 theme cell 69:72 arg1 biosynthesis 79:90 secondary cell wall biosynthesis 59:90 secondary cell wall biosynthesis 59:90 CEF3 is involved in membrane trafficking and essential for secondary cell wall biosynthesis and its mutation enhanced biomass enzymatic saccharification in rice. 36242043 4 26 theme Map-based 728:736 arg1 cloning 738:744 Map-based cloning 728:744 Map-based cloning 728:744 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 2 27 from formation 438:446 arg1 plants 451:456 plants 451:456 plants 451:456 Membrane trafficking plays key roles in SCWs biosynthesis, but information association membrane trafficking and SCWs formation in plants is limited. 36242043 11 28 theme genetic 1828:1834 arg1 modification 1836:1847 genetic modification 1828:1847 genetic modification of SCWs in bioenergy crops 1828:1874 Therefore, the study of the function of CEF3 can provide a strategy for genetic modification of SCWs in bioenergy crops. 36242043 9 29 theme synthase 1355:1362 arg1 subunit 1374:1380 cellulose synthase catalytic subunit 9 1345:1382 cellulose synthase catalytic subunit 9 (OsCESA9) 1345:1392 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 9 29 theme synthase 1355:1362 arg1 OsCESA9 1385:1391 OsCESA9 1385:1391 OsCESA9 1385:1391 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 2 30 theme SCWs 433:436 arg1 formation 438:446 SCWs formation 433:446 SCWs formation 433:446 Membrane trafficking plays key roles in SCWs biosynthesis, but information association membrane trafficking and SCWs formation in plants is limited. 36242043 9 31 theme subunit 1374:1380 arg1 abundance 1332:1340 the abundance 1328:1340 the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems 1328:1434 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 5 32 theme enzymatic 925:933 arg1 saccharification 935:950 biomass enzymatic saccharification 917:950 biomass enzymatic saccharification 917:950 The saccharification assays revealed that CEF3 mutation can improve biomass enzymatic saccharification. 36242043 6 33 theme developmental 1055:1067 arg1 stages 1069:1074 different developmental stages 1045:1074 different developmental stages 1045:1074 Expression pattern analysis indicated that CEF3 is ubiquitously expressed in many organs at different developmental stages. 36242043 3 34 theme growth 595:600 arg1 retardation 602:612 growth retardation 595:612 growth retardation 595:612 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 10 35 theme enzymatic 1713:1721 arg1 saccharification 1723:1738 biomass enzymatic saccharification 1705:1738 biomass enzymatic saccharification in rice plants 1705:1753 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 0 36 theme membrane 20:27 arg1 trafficking 29:39 membrane trafficking 20:39 membrane trafficking 20:39 CEF3 is involved in membrane trafficking and essential for secondary cell wall biosynthesis and its mutation enhanced biomass enzymatic saccharification in rice. 36242043 10 37 theme cellulose 1557:1565 arg1 biosynthesis 1593:1604 normal cellulose and other polysaccharides biosynthesis 1550:1604 normal cellulose and other polysaccharides biosynthesis of the secondary cell wall 1550:1631 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 4 38 theme Arabidopsis 797:807 arg1 DEFECTIVE2 830:839 Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 797:839 Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2) 797:846 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 4 38 theme Arabidopsis 797:807 arg1 SCD2 842:845 SCD2 842:845 SCD2 842:845 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 1 39 theme cell 302:305 arg1 SCWs 314:317 SCWs 314:317 SCWs 314:317 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 1 39 theme cell 302:305 arg1 walls 307:311 secondary cell walls 292:311 secondary cell walls (SCWs) 292:318 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 3 40 theme culm 626:629 arg1 phenotype 631:639 fragile culm phenotype 618:639 fragile culm phenotype 618:639 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 1 41 theme crops 214:218 arg1 crops 214:218 the most important staple food crops 183:218 the most important staple food crops 183:218 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 1 41 theme crops 214:218 arg1 one 176:178 one 176:178 one 176:178 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 2 42 theme key 348:350 arg1 roles 352:356 key roles 348:356 key roles 348:356 Membrane trafficking plays key roles in SCWs biosynthesis, but information association membrane trafficking and SCWs formation in plants is limited. 36242043 10 43 dep CONCLUSIONS 1437:1447 arg1 demonstrated 1464:1475 demonstrated 1464:1475 has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants 1460:1753 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 8 44 theme FM4-64 1155:1160 arg1 assay 1169:1173 The FM4-64 uptake assay 1151:1173 The FM4-64 uptake assay 1151:1173 The FM4-64 uptake assay revealed CEF3 is involved in endocytosis. 36242043 2 45 from association 396:406 arg1 plants 451:456 plants 451:456 plants 451:456 Membrane trafficking plays key roles in SCWs biosynthesis, but information association membrane trafficking and SCWs formation in plants is limited. 36242043 10 46 theme other 1571:1575 arg1 polysaccharides 1577:1591 other polysaccharides 1571:1591 other polysaccharides 1571:1591 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 3 47 theme altered 660:666 arg1 composition 678:688 significantly altered cell wall composition 646:688 significantly altered cell wall composition 646:688 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 10 48 theme cell 1623:1626 arg1 wall 1628:1631 the secondary cell wall 1609:1631 the secondary cell wall 1609:1631 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 7 49 theme Golgi-localized 1126:1140 arg1 protein 1142:1148 a Golgi-localized protein 1124:1148 a Golgi-localized protein 1124:1148 Subcellular localization revealed that CEF3 is a Golgi-localized protein. 36242043 7 49 theme Golgi-localized 1126:1140 arg1 CEF3 1116:1119 CEF3 1116:1119 CEF3 1116:1119 Subcellular localization revealed that CEF3 is a Golgi-localized protein. 36242043 2 50 dep association 396:406 arg1 trafficking 417:427 membrane trafficking 408:427 membrane trafficking 408:427 Membrane trafficking plays key roles in SCWs biosynthesis, but information association membrane trafficking and SCWs formation in plants is limited. 36242043 3 51 theme function 507:514 arg1 characterization 516:531 the function characterization 503:531 the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness 503:725 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 1 52 theme agronomic 244:252 arg1 residues 262:269 agronomic biomass residues 244:269 agronomic biomass residues that contain lots of secondary cell walls (SCWs) 244:318 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 11 53 from crops 1870:1874 arg1 modification 1836:1847 genetic modification 1828:1847 genetic modification of SCWs in bioenergy crops 1828:1874 Therefore, the study of the function of CEF3 can provide a strategy for genetic modification of SCWs in bioenergy crops. 36242043 4 54 theme STOMATAL 809:816 arg1 DEFECTIVE2 830:839 Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 797:839 Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2) 797:846 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 4 54 theme STOMATAL 809:816 arg1 SCD2 842:845 SCD2 842:845 SCD2 842:845 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 3 55 theme wall 673:676 arg1 composition 678:688 significantly altered cell wall composition 646:688 significantly altered cell wall composition 646:688 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 3 56 theme rice 538:541 arg1 mutant 543:548 a rice mutant 536:548 a rice mutant 536:548 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 4 57 theme DEFECTIVE2 830:839 arg1 protein 786:792 a homologous protein 773:792 a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2) 773:846 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 4 57 theme DEFECTIVE2 830:839 arg1 CEF3 760:763 CEF3 760:763 CEF3 760:763 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 0 58 theme biomass 118:124 arg1 saccharification 136:151 biomass enzymatic saccharification 118:151 biomass enzymatic saccharification 118:151 CEF3 is involved in membrane trafficking and essential for secondary cell wall biosynthesis and its mutation enhanced biomass enzymatic saccharification in rice. 36242043 6 59 theme pattern 964:970 arg1 analysis 972:979 Expression pattern analysis 953:979 Expression pattern analysis 953:979 Expression pattern analysis indicated that CEF3 is ubiquitously expressed in many organs at different developmental stages. 36242043 3 60 theme secondary 702:710 arg1 thickness 717:725 reduced secondary wall thickness 694:725 reduced secondary wall thickness 694:725 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 1 61 theme staple 202:207 arg1 crops 214:218 the most important staple food crops 183:218 the most important staple food crops 183:218 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 9 62 from abundance 1332:1340 arg1 systems 1428:1434 the endomembrane systems 1411:1434 the endomembrane systems 1411:1434 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 9 62 from abundance 1332:1340 arg1 PM 1401:1402 the PM 1397:1402 the PM 1397:1402 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 10 63 theme CEF3 1658:1661 arg1 manipulation 1642:1653 manipulation 1642:1653 manipulation of CEF3 1642:1661 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 9 64 theme synthesis-related 1275:1291 arg1 expression 1299:1308 cellulose synthesis-related genes expression 1265:1308 cellulose synthesis-related genes expression 1265:1308 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 5 65 theme CEF3 891:894 arg1 mutation 896:903 CEF3 mutation 891:903 CEF3 mutation 891:903 The saccharification assays revealed that CEF3 mutation can improve biomass enzymatic saccharification. 36242043 11 66 theme CEF3 1796:1799 arg1 function 1784:1791 the function 1780:1791 the function of CEF3 1780:1799 Therefore, the study of the function of CEF3 can provide a strategy for genetic modification of SCWs in bioenergy crops. 36242043 0 67 theme secondary 59:67 arg1 biosynthesis 79:90 secondary cell wall biosynthesis 59:90 secondary cell wall biosynthesis 59:90 CEF3 is involved in membrane trafficking and essential for secondary cell wall biosynthesis and its mutation enhanced biomass enzymatic saccharification in rice. 36242043 5 68 theme saccharification 853:868 arg1 assays 870:875 The saccharification assays 849:875 The saccharification assays 849:875 The saccharification assays revealed that CEF3 mutation can improve biomass enzymatic saccharification. 36242043 11 69 theme function 1784:1791 arg1 study 1771:1775 the study 1767:1775 the study of the function of CEF3 1767:1799 Therefore, the study of the function of CEF3 can provide a strategy for genetic modification of SCWs in bioenergy crops. 36242043 0 70 theme wall 74:77 arg1 biosynthesis 79:90 secondary cell wall biosynthesis 59:90 secondary cell wall biosynthesis 59:90 CEF3 is involved in membrane trafficking and essential for secondary cell wall biosynthesis and its mutation enhanced biomass enzymatic saccharification in rice. 36242043 9 71 theme cellulose 1345:1353 arg1 subunit 1374:1380 cellulose synthase catalytic subunit 9 1345:1382 cellulose synthase catalytic subunit 9 (OsCESA9) 1345:1392 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 9 71 theme cellulose 1345:1353 arg1 OsCESA9 1385:1391 OsCESA9 1385:1391 OsCESA9 1385:1391 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 3 72 dep RESULTS 470:476 arg1 report 496:501 report 496:501 report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness 496:725 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 2 73 theme SCWs 361:364 arg1 biosynthesis 366:377 SCWs biosynthesis 361:377 SCWs biosynthesis 361:377 Membrane trafficking plays key roles in SCWs biosynthesis, but information association membrane trafficking and SCWs formation in plants is limited. 36242043 9 74 theme catalytic 1364:1372 arg1 subunit 1374:1380 cellulose synthase catalytic subunit 9 1345:1382 cellulose synthase catalytic subunit 9 (OsCESA9) 1345:1392 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 9 74 theme catalytic 1364:1372 arg1 OsCESA9 1385:1391 OsCESA9 1385:1391 OsCESA9 1385:1391 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36242043 5 75 theme biomass 917:923 arg1 saccharification 935:950 biomass enzymatic saccharification 917:950 biomass enzymatic saccharification 917:950 The saccharification assays revealed that CEF3 mutation can improve biomass enzymatic saccharification. 36242043 1 76 dep BACKGROUND 162:171 arg1 produces 226:233 produces 226:233 produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs) 226:318 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 10 77 theme cellulose 1675:1683 arg1 content 1685:1691 cellulose content 1675:1691 cellulose content 1675:1691 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 2 78 theme membrane 408:415 arg1 trafficking 417:427 membrane trafficking 408:427 membrane trafficking 408:427 Membrane trafficking plays key roles in SCWs biosynthesis, but information association membrane trafficking and SCWs formation in plants is limited. 36242043 2 79 theme information 384:394 arg1 association 396:406 information association 384:406 information association 384:406 Membrane trafficking plays key roles in SCWs biosynthesis, but information association membrane trafficking and SCWs formation in plants is limited. 36242043 6 80 theme different 1045:1053 arg1 stages 1069:1074 different developmental stages 1045:1074 different developmental stages 1045:1074 Expression pattern analysis indicated that CEF3 is ubiquitously expressed in many organs at different developmental stages. 36242043 10 81 theme membrane 1507:1514 arg1 trafficking 1516:1526 the membrane trafficking 1503:1526 the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants 1503:1753 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 10 81 theme membrane 1507:1514 arg1 essential 1536:1544 essential 1536:1544 essential 1536:1544 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 4 82 theme homologous 775:784 arg1 protein 786:792 a homologous protein 773:792 a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2) 773:846 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 4 82 theme homologous 775:784 arg1 CEF3 760:763 CEF3 760:763 CEF3 760:763 Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). 36242043 10 83 theme biomass 1705:1711 arg1 saccharification 1723:1738 biomass enzymatic saccharification 1705:1738 biomass enzymatic saccharification in rice plants 1705:1753 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 1 84 theme secondary 292:300 arg1 SCWs 314:317 SCWs 314:317 SCWs 314:317 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 1 84 theme secondary 292:300 arg1 walls 307:311 secondary cell walls 292:311 secondary cell walls (SCWs) 292:318 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 7 85 theme Subcellular 1077:1087 arg1 localization 1089:1100 Subcellular localization 1077:1100 Subcellular localization 1077:1100 Subcellular localization revealed that CEF3 is a Golgi-localized protein. 36242043 10 86 theme normal 1550:1555 arg1 biosynthesis 1593:1604 normal cellulose and other polysaccharides biosynthesis 1550:1604 normal cellulose and other polysaccharides biosynthesis of the secondary cell wall 1550:1631 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 3 87 theme fragile 618:624 arg1 phenotype 631:639 fragile culm phenotype 618:639 fragile culm phenotype 618:639 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 1 88 theme walls 307:311 arg1 lots 284:287 lots 284:287 lots of secondary cell walls (SCWs) 284:318 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 1 88 theme walls 307:311 arg1 SCWs 314:317 SCWs 314:317 SCWs 314:317 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 1 88 theme walls 307:311 arg1 walls 307:311 secondary cell walls 292:311 secondary cell walls (SCWs) 292:318 BACKGROUND As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). 36242043 10 89 theme rice 1743:1746 arg1 plants 1748:1753 rice plants 1743:1753 rice plants 1743:1753 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 8 90 theme uptake 1162:1167 arg1 assay 1169:1173 The FM4-64 uptake assay 1151:1173 The FM4-64 uptake assay 1151:1173 The FM4-64 uptake assay revealed CEF3 is involved in endocytosis. 36242043 10 91 theme polysaccharides 1577:1591 arg1 biosynthesis 1593:1604 normal cellulose and other polysaccharides biosynthesis 1550:1604 normal cellulose and other polysaccharides biosynthesis of the secondary cell wall 1550:1631 CONCLUSIONS This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. 36242043 3 92 with phenotype 631:639 arg1 thickness 717:725 reduced secondary wall thickness 694:725 reduced secondary wall thickness 694:725 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 3 92 with phenotype 631:639 arg1 composition 678:688 significantly altered cell wall composition 646:688 significantly altered cell wall composition 646:688 RESULTS In this study, we report the function characterization of a rice mutant, culm easily fragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. 36242043 9 93 theme endomembrane 1415:1426 arg1 systems 1428:1434 the endomembrane systems 1411:1434 the endomembrane systems 1411:1434 Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. 36834769 9 0 theme cell 909:912 arg1 walls 914:918 The cell walls 905:918 The cell walls of the head cells and stalk cells 905:952 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 5 1 theme wall 636:639 arg1 polysaccharides 641:655 the major cell wall polysaccharides 621:655 the major cell wall polysaccharides 621:655 Fluorescence microscopy revealed the localization of carbohydrate epitopes associated with the major cell wall polysaccharides and glycoproteins. 36834769 1 2 theme Aldrovanda 218:227 arg1 Droseracee 241:250 Droseracee 241:250 Droseracee 241:250 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 1 2 theme Aldrovanda 218:227 arg1 vesiculosa 229:238 the aquatic carnivorous plant Aldrovanda vesiculosa 188:238 the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee) 188:251 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 13 3 theme trichome 1544:1551 arg1 cells 1553:1557 these trichome cells 1538:1557 these trichome cells 1538:1557 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 12 4 theme bifid 1367:1371 arg1 trichomes 1373:1381 bifid trichomes 1367:1381 bifid trichomes 1367:1381 The presence of endodermal cells and transfer cells supports the idea that bifid trichomes actively transport solutes, which are polysaccharide in nature. 36834769 9 5 theme head 927:930 arg1 cells 932:936 head cells 927:936 head cells 927:936 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 7 6 theme bifid 824:828 arg1 trichomes 830:838 the bifid trichomes 820:838 the bifid trichomes 820:838 Cell wall ingrowths occurred in all cell types of the bifid trichomes. 36834769 1 7 theme trap 153:156 arg1 surface 158:164 the external (abaxial) trap surface 130:164 the external (abaxial) trap surface 130:164 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 12 8 theme transfer 1329:1336 arg1 cells 1338:1342 transfer cells 1329:1342 transfer cells 1329:1342 The presence of endodermal cells and transfer cells supports the idea that bifid trichomes actively transport solutes, which are polysaccharide in nature. 36834769 4 9 used used 493:496 arg2 microscopy 478:487 electron microscopy 469:487 electron microscopy 469:487 Light and electron microscopy was used to show the trichome structure. 36834769 4 9 used used 493:496 arg2 Light 459:463 Light 459:463 Light 459:463 Light and electron microscopy was used to show the trichome structure. 36834769 13 10 theme cell 1524:1527 arg1 walls 1529:1533 the cell walls 1520:1533 the cell walls in these trichome cells 1520:1557 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 14 11 theme carnivorous 1834:1844 arg1 plants 1846:1851 other carnivorous plants 1828:1851 other carnivorous plants 1828:1851 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 9 12 theme cells 948:952 arg1 walls 914:918 The cell walls 905:918 The cell walls of the head cells and stalk cells 905:952 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 7 13 theme cell 806:809 arg1 types 811:815 all cell types 802:815 all cell types of the bifid trichomes 802:838 Cell wall ingrowths occurred in all cell types of the bifid trichomes. 36834769 9 14 from homogalacturonans 1075:1091 arg1 poor 1035:1038 poor 1035:1038 poor 1035:1038 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 12 15 from nature 1439:1444 arg1 polysaccharide 1421:1434 polysaccharide 1421:1434 polysaccharide 1421:1434 The presence of endodermal cells and transfer cells supports the idea that bifid trichomes actively transport solutes, which are polysaccharide in nature. 36834769 12 16 theme cells 1319:1323 arg1 presence 1296:1303 The presence 1292:1303 The presence of endodermal cells and transfer cells 1292:1342 The presence of endodermal cells and transfer cells supports the idea that bifid trichomes actively transport solutes, which are polysaccharide in nature. 36834769 9 17 theme arabinogalactan 973:987 arg1 AGPs 999:1002 AGPs 999:1002 AGPs 999:1002 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 9 17 theme arabinogalactan 973:987 arg1 proteins 989:996 arabinogalactan proteins 973:996 arabinogalactan proteins (AGPs) 973:1003 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 13 18 from role 1594:1597 arg1 function 1627:1634 plant function 1621:1634 plant function 1621:1634 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 13 19 theme plant 1490:1494 arg1 molecules 1506:1514 plant signaling molecules 1490:1514 plant signaling molecules 1490:1514 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 13 20 theme active 1573:1578 arg1 role 1594:1597 the active and important role 1569:1597 the active and important role of these trichomes in plant function 1569:1634 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 1 21 theme external 134:141 arg1 surface 158:164 the external (abaxial) trap surface 130:164 the external (abaxial) trap surface 130:164 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 1 22 theme abaxial 144:150 arg1 surface 158:164 the external (abaxial) trap surface 130:164 the external (abaxial) trap surface 130:164 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 8 23 theme Trichome 841:848 arg1 cells 850:854 Trichome cells 841:854 Trichome cells 841:854 Trichome cells differed in the composition of their cell walls. 36834769 4 24 theme electron 469:476 arg1 microscopy 478:487 electron microscopy 469:487 electron microscopy 469:487 Light and electron microscopy was used to show the trichome structure. 36834769 5 25 theme carbohydrate 583:594 arg1 epitopes 596:603 carbohydrate epitopes 583:603 carbohydrate epitopes associated with the major cell wall polysaccharides and glycoproteins 583:673 Fluorescence microscopy revealed the localization of carbohydrate epitopes associated with the major cell wall polysaccharides and glycoproteins. 36834769 0 26 from Aldrovanda 50:59 arg1 Analysis 19:26 Immunocytochemical Analysis 0:26 Immunocytochemical Analysis of Bifid Trichomes in Aldrovanda vesiculosa L. 0:73 Immunocytochemical Analysis of Bifid Trichomes in Aldrovanda vesiculosa L. Traps. 36834769 3 27 from gap 336:338 arg1 literature 347:356 the literature 343:356 the literature concerning the immunocytochemistry of the bifid trichomes 343:414 This study aimed to fill the gap in the literature concerning the immunocytochemistry of the bifid trichomes and compare them with digestive trichomes. 36834769 5 28 theme Fluorescence 530:541 arg1 microscopy 543:552 Fluorescence microscopy 530:552 Fluorescence microscopy 530:552 Fluorescence microscopy revealed the localization of carbohydrate epitopes associated with the major cell wall polysaccharides and glycoproteins. 36834769 0 29 from Trichomes 37:45 arg1 Aldrovanda 50:59 Aldrovanda 50:59 Aldrovanda 50:59 Immunocytochemical Analysis of Bifid Trichomes in Aldrovanda vesiculosa L. Traps. 36834769 13 30 theme AGPs 1463:1466 arg1 presence 1451:1458 The presence 1447:1458 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells 1447:1557 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 0 31 theme Immunocytochemical 0:17 arg1 Analysis 19:26 Immunocytochemical Analysis 0:26 Immunocytochemical Analysis of Bifid Trichomes in Aldrovanda vesiculosa L. 0:73 Immunocytochemical Analysis of Bifid Trichomes in Aldrovanda vesiculosa L. Traps. 36834769 9 32 theme low- 1048:1051 arg1 HGs 1094:1096 HGs 1094:1096 HGs 1094:1096 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 9 32 theme low- 1048:1051 arg1 homogalacturonans 1075:1091 both low- and highly-esterified homogalacturonans 1043:1091 both low- and highly-esterified homogalacturonans (HGs) 1043:1097 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 1 33 theme bifid 104:108 arg1 bifids 96:101 The two-armed bifids 82:101 The two-armed bifids (bifid trichomes) 82:119 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 1 33 theme bifid 104:108 arg1 trichomes 110:118 bifid trichomes 104:118 bifid trichomes 104:118 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 8 34 theme cell 893:896 arg1 walls 898:902 their cell walls 887:902 their cell walls 887:902 Trichome cells differed in the composition of their cell walls. 36834769 9 35 theme highly-esterified 1057:1073 arg1 HGs 1094:1096 HGs 1094:1096 HGs 1094:1096 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 9 35 theme highly-esterified 1057:1073 arg1 homogalacturonans 1075:1091 both low- and highly-esterified homogalacturonans 1043:1091 both low- and highly-esterified homogalacturonans (HGs) 1043:1097 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 3 36 theme trichomes 406:414 arg1 immunocytochemistry 373:391 the immunocytochemistry 369:391 the immunocytochemistry of the bifid trichomes 369:414 This study aimed to fill the gap in the literature concerning the immunocytochemistry of the bifid trichomes and compare them with digestive trichomes. 36834769 0 37 theme Trichomes 37:45 arg1 Analysis 19:26 Immunocytochemical Analysis 0:26 Immunocytochemical Analysis of Bifid Trichomes in Aldrovanda vesiculosa L. 0:73 Immunocytochemical Analysis of Bifid Trichomes in Aldrovanda vesiculosa L. Traps. 36834769 11 38 from ingrowths 1214:1222 arg1 cells 1237:1241 the basal cells 1227:1241 the basal cells 1227:1241 The cell wall ingrowths in the basal cells were significantly enriched with hemicelluloses. 36834769 10 39 dep hemicelluloses 1150:1163 arg1 galactoxyloglucan 1181:1197 galactoxyloglucan 1181:1197 galactoxyloglucan 1181:1197 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 10 39 dep hemicelluloses 1150:1163 arg1 xyloglucan 1166:1175 xyloglucan 1166:1175 xyloglucan 1166:1175 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 10 39 dep hemicelluloses 1150:1163 arg1 hemicelluloses 1150:1163 hemicelluloses 1150:1163 hemicelluloses: xyloglucan and galactoxyloglucan 1150:1197 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 0 40 dep Aldrovanda 50:59 arg1 L. 72:73 Aldrovanda vesiculosa L. 50:73 Aldrovanda vesiculosa L. 50:73 Immunocytochemical Analysis of Bifid Trichomes in Aldrovanda vesiculosa L. Traps. 36834769 7 41 theme Cell 770:773 arg1 ingrowths 780:788 Cell wall ingrowths 770:788 Cell wall ingrowths 770:788 Cell wall ingrowths occurred in all cell types of the bifid trichomes. 36834769 11 42 theme cell 1204:1207 arg1 ingrowths 1214:1222 The cell wall ingrowths 1200:1222 The cell wall ingrowths in the basal cells 1200:1241 The cell wall ingrowths in the basal cells were significantly enriched with hemicelluloses. 36834769 14 43 theme trap 1719:1722 arg1 walls 1729:1733 trap cell walls 1719:1733 trap cell walls 1719:1733 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 13 44 from walls 1529:1533 arg1 cells 1553:1557 these trichome cells 1538:1557 these trichome cells 1538:1557 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 9 45 from poor 1035:1038 arg1 HGs 1094:1096 HGs 1094:1096 HGs 1094:1096 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 9 45 from poor 1035:1038 arg1 homogalacturonans 1075:1091 both low- and highly-esterified homogalacturonans 1043:1091 both low- and highly-esterified homogalacturonans (HGs) 1043:1097 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 2 46 theme mucilage 287:294 arg1 trichomes 296:304 mucilage trichomes 287:304 mucilage trichomes 287:304 These trichomes play the role of mucilage trichomes. 36834769 14 47 from capture 1785:1791 arg1 plants 1846:1851 other carnivorous plants 1828:1851 other carnivorous plants 1828:1851 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 14 47 from capture 1785:1791 arg1 vesiculosa 1813:1822 A. vesiculosa 1810:1822 A. vesiculosa 1810:1822 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 14 48 from digestion 1797:1805 arg1 plants 1846:1851 other carnivorous plants 1828:1851 other carnivorous plants 1828:1851 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 14 48 from digestion 1797:1805 arg1 vesiculosa 1813:1822 A. vesiculosa 1810:1822 A. vesiculosa 1810:1822 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 1 49 theme aquatic 192:198 arg1 Droseracee 241:250 Droseracee 241:250 Droseracee 241:250 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 1 49 theme aquatic 192:198 arg1 vesiculosa 229:238 the aquatic carnivorous plant Aldrovanda vesiculosa 188:238 the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee) 188:251 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 7 50 theme wall 775:778 arg1 ingrowths 780:788 Cell wall ingrowths 770:788 Cell wall ingrowths 770:788 Cell wall ingrowths occurred in all cell types of the bifid trichomes. 36834769 5 51 theme cell 631:634 arg1 polysaccharides 641:655 the major cell wall polysaccharides 621:655 the major cell wall polysaccharides 621:655 Fluorescence microscopy revealed the localization of carbohydrate epitopes associated with the major cell wall polysaccharides and glycoproteins. 36834769 1 52 theme plant 212:216 arg1 Droseracee 241:250 Droseracee 241:250 Droseracee 241:250 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 1 52 theme plant 212:216 arg1 vesiculosa 229:238 the aquatic carnivorous plant Aldrovanda vesiculosa 188:238 the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee) 188:251 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 13 53 attach presence 1451:1458 arg1 walls 1529:1533 the cell walls 1520:1533 the cell walls in these trichome cells 1520:1557 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 13 53 attach presence 1451:1458 arg2 AGPs 1463:1466 AGPs 1463:1466 AGPs (which are considered plant signaling molecules) 1463:1515 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 1 54 theme vesiculosa 229:238 arg1 surface 158:164 the external (abaxial) trap surface 130:164 the external (abaxial) trap surface 130:164 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 1 54 theme vesiculosa 229:238 arg1 petiole 167:173 petiole 167:173 petiole 167:173 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 1 54 theme vesiculosa 229:238 arg1 stem 180:183 stem 180:183 stem 180:183 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 9 55 theme cells 932:936 arg1 walls 914:918 The cell walls 905:918 The cell walls of the head cells and stalk cells 905:952 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 10 56 from walls 1109:1113 arg1 cells 1131:1135 the trichome cells 1118:1135 the trichome cells 1118:1135 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 7 57 theme trichomes 830:838 arg1 types 811:815 all cell types 802:815 all cell types of the bifid trichomes 802:838 Cell wall ingrowths occurred in all cell types of the bifid trichomes. 36834769 14 58 theme walls 1729:1733 arg1 architecture 1703:1714 the molecular architecture 1689:1714 the molecular architecture of trap cell walls 1689:1733 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 5 59 theme major 625:629 arg1 polysaccharides 641:655 the major cell wall polysaccharides 621:655 the major cell wall polysaccharides 621:655 Fluorescence microscopy revealed the localization of carbohydrate epitopes associated with the major cell wall polysaccharides and glycoproteins. 36834769 9 60 theme stalk 942:946 arg1 cells 948:952 stalk cells 942:952 stalk cells 942:952 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 14 61 theme other 1828:1832 arg1 plants 1846:1851 other carnivorous plants 1828:1851 other carnivorous plants 1828:1851 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 12 62 theme cells 1338:1342 arg1 presence 1296:1303 The presence 1292:1303 The presence of endodermal cells and transfer cells 1292:1342 The presence of endodermal cells and transfer cells supports the idea that bifid trichomes actively transport solutes, which are polysaccharide in nature. 36834769 13 63 theme signaling 1496:1504 arg1 molecules 1506:1514 plant signaling molecules 1490:1514 plant signaling molecules 1490:1514 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 10 64 from rich 1142:1145 arg1 galactoxyloglucan 1181:1197 galactoxyloglucan 1181:1197 galactoxyloglucan 1181:1197 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 10 64 from rich 1142:1145 arg1 xyloglucan 1166:1175 xyloglucan 1166:1175 xyloglucan 1166:1175 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 10 64 from rich 1142:1145 arg1 hemicelluloses 1150:1163 hemicelluloses 1150:1163 hemicelluloses: xyloglucan and galactoxyloglucan 1150:1197 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 14 65 theme Future 1637:1642 arg1 research 1644:1651 Future research 1637:1651 Future research 1637:1651 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 12 66 theme endodermal 1308:1317 arg1 cells 1319:1323 endodermal cells 1308:1323 endodermal cells 1308:1323 The presence of endodermal cells and transfer cells supports the idea that bifid trichomes actively transport solutes, which are polysaccharide in nature. 36834769 10 67 from hemicelluloses 1150:1163 arg1 rich 1142:1145 rich 1142:1145 rich 1142:1145 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 10 67 from hemicelluloses 1150:1163 arg1 walls 1109:1113 The cell walls 1100:1113 The cell walls in the trichome cells 1100:1135 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 14 68 theme trap 1759:1762 arg1 development 1764:1774 trap development 1759:1774 trap development 1759:1774 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 14 69 theme prey 1780:1783 arg1 capture 1785:1791 prey capture 1780:1791 prey capture 1780:1791 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 13 70 from presence 1451:1458 arg1 walls 1529:1533 the cell walls 1520:1533 the cell walls in these trichome cells 1520:1557 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 5 71 gly glycoproteins 661:673 arg1 glycoproteins 661:673 glycoproteins 661:673 glycoproteins 661:673 Fluorescence microscopy revealed the localization of carbohydrate epitopes associated with the major cell wall polysaccharides and glycoproteins. 36834769 0 72 from Analysis 19:26 arg1 Aldrovanda 50:59 Aldrovanda 50:59 Aldrovanda 50:59 Immunocytochemical Analysis of Bifid Trichomes in Aldrovanda vesiculosa L. Traps. 36834769 11 73 theme basal 1231:1235 arg1 cells 1237:1241 the basal cells 1227:1241 the basal cells 1227:1241 The cell wall ingrowths in the basal cells were significantly enriched with hemicelluloses. 36834769 9 74 dep cells 932:936 arg1 the 923:925 the 923:925 the 923:925 The cell walls of the head cells and stalk cells were enriched with arabinogalactan proteins (AGPs); however, they were generally poor in both low- and highly-esterified homogalacturonans (HGs). 36834769 6 75 theme basal 700:704 arg1 cells 706:710 the basal cells 696:710 the basal cells 696:710 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 6 75 theme basal 700:704 arg1 cells 763:767 endodermal cells 752:767 endodermal cells 752:767 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 6 75 theme basal 700:704 arg1 cells 686:690 The stalk cells 676:690 The stalk cells 676:690 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 5 76 theme epitopes 596:603 arg1 localization 567:578 the localization 563:578 the localization of carbohydrate epitopes associated with the major cell wall polysaccharides and glycoproteins 563:673 Fluorescence microscopy revealed the localization of carbohydrate epitopes associated with the major cell wall polysaccharides and glycoproteins. 36834769 13 77 theme plant 1621:1625 arg1 function 1627:1634 plant function 1621:1634 plant function 1621:1634 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 14 78 theme molecular 1693:1701 arg1 architecture 1703:1714 the molecular architecture 1689:1714 the molecular architecture of trap cell walls 1689:1733 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 3 79 theme bifid 400:404 arg1 trichomes 406:414 the bifid trichomes 396:414 the bifid trichomes 396:414 This study aimed to fill the gap in the literature concerning the immunocytochemistry of the bifid trichomes and compare them with digestive trichomes. 36834769 1 80 theme two-armed 86:94 arg1 bifids 96:101 The two-armed bifids 82:101 The two-armed bifids (bifid trichomes) 82:119 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 1 80 theme two-armed 86:94 arg1 trichomes 110:118 bifid trichomes 104:118 bifid trichomes 104:118 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 4 81 theme trichome 510:517 arg1 structure 519:527 the trichome structure 506:527 the trichome structure 506:527 Light and electron microscopy was used to show the trichome structure. 36834769 6 82 theme stalk 680:684 arg1 cells 763:767 endodermal cells 752:767 endodermal cells 752:767 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 6 82 theme stalk 680:684 arg1 cells 706:710 the basal cells 696:710 the basal cells 696:710 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 6 82 theme stalk 680:684 arg1 cells 686:690 The stalk cells 676:690 The stalk cells 676:690 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 0 83 theme Bifid 31:35 arg1 Trichomes 37:45 Bifid Trichomes 31:45 Bifid Trichomes in Aldrovanda vesiculosa L. 31:73 Immunocytochemical Analysis of Bifid Trichomes in Aldrovanda vesiculosa L. Traps. 36834769 14 84 theme cell 1724:1727 arg1 walls 1729:1733 trap cell walls 1719:1733 trap cell walls 1719:1733 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 13 85 theme trichomes 1608:1616 arg1 role 1594:1597 the active and important role 1569:1597 the active and important role of these trichomes in plant function 1569:1634 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 6 86 theme endodermal 752:761 arg1 cells 763:767 endodermal cells 752:767 endodermal cells 752:767 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 6 86 theme endodermal 752:761 arg1 cells 706:710 the basal cells 696:710 the basal cells 696:710 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 6 86 theme endodermal 752:761 arg1 cells 686:690 The stalk cells 676:690 The stalk cells 676:690 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 10 87 theme cell 1104:1107 arg1 rich 1142:1145 rich 1142:1145 rich 1142:1145 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 10 87 theme cell 1104:1107 arg1 walls 1109:1113 The cell walls 1100:1113 The cell walls in the trichome cells 1100:1135 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 8 88 theme walls 898:902 arg1 composition 872:882 the composition 868:882 the composition of their cell walls 868:902 Trichome cells differed in the composition of their cell walls. 36834769 11 89 theme wall 1209:1212 arg1 ingrowths 1214:1222 The cell wall ingrowths 1200:1222 The cell wall ingrowths in the basal cells 1200:1241 The cell wall ingrowths in the basal cells were significantly enriched with hemicelluloses. 36834769 2 90 theme trichomes 296:304 arg1 role 279:282 the role 275:282 the role of mucilage trichomes 275:304 These trichomes play the role of mucilage trichomes. 36834769 13 91 theme important 1584:1592 arg1 role 1594:1597 the active and important role 1569:1597 the active and important role of these trichomes in plant function 1569:1634 The presence of AGPs (which are considered plant signaling molecules) in the cell walls in these trichome cells indicates the active and important role of these trichomes in plant function. 36834769 6 92 theme trichomes 719:727 arg1 cells 706:710 the basal cells 696:710 the basal cells 696:710 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 6 92 theme trichomes 719:727 arg1 cells 763:767 endodermal cells 752:767 endodermal cells 752:767 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 6 92 theme trichomes 719:727 arg1 cells 686:690 The stalk cells 676:690 The stalk cells 676:690 The stalk cells and the basal cells of the trichomes were differentiated as endodermal cells. 36834769 3 93 theme digestive 438:446 arg1 trichomes 448:456 digestive trichomes 438:456 digestive trichomes 438:456 This study aimed to fill the gap in the literature concerning the immunocytochemistry of the bifid trichomes and compare them with digestive trichomes. 36834769 10 94 theme trichome 1122:1129 arg1 cells 1131:1135 the trichome cells 1118:1135 the trichome cells 1118:1135 The cell walls in the trichome cells were rich in hemicelluloses: xyloglucan and galactoxyloglucan. 36834769 12 95 from polysaccharide 1421:1434 arg1 nature 1439:1444 nature 1439:1444 nature 1439:1444 The presence of endodermal cells and transfer cells supports the idea that bifid trichomes actively transport solutes, which are polysaccharide in nature. 36834769 14 96 from development 1764:1774 arg1 plants 1846:1851 other carnivorous plants 1828:1851 other carnivorous plants 1828:1851 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 14 96 from development 1764:1774 arg1 vesiculosa 1813:1822 A. vesiculosa 1810:1822 A. vesiculosa 1810:1822 Future research should focus on the question of how the molecular architecture of trap cell walls changes in cells during trap development and prey capture and digestion in A. vesiculosa and other carnivorous plants. 36834769 1 97 theme carnivorous 200:210 arg1 Droseracee 241:250 Droseracee 241:250 Droseracee 241:250 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36834769 1 97 theme carnivorous 200:210 arg1 vesiculosa 229:238 the aquatic carnivorous plant Aldrovanda vesiculosa 188:238 the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee) 188:251 The two-armed bifids (bifid trichomes) occur on the external (abaxial) trap surface, petiole, and stem of the aquatic carnivorous plant Aldrovanda vesiculosa (Droseracee). 36781010 14 0 dep function 2088:2095 arg1 creatinine 2107:2116 creatinine 2107:2116 creatinine 2107:2116 In addition to improving kidney function (urea and creatinine), algal extracts enhance fat metabolism (triglycerides and cholesterol). 36781010 14 0 dep function 2088:2095 arg1 urea 2098:2101 urea 2098:2101 urea 2098:2101 In addition to improving kidney function (urea and creatinine), algal extracts enhance fat metabolism (triglycerides and cholesterol). 36781010 5 1 theme excellent 646:654 arg1 Macroalgae 619:628 Macroalgae 619:628 Macroalgae 619:628 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 5 1 theme excellent 646:654 arg1 sources 656:662 potentially excellent sources 634:662 potentially excellent sources of bioactive substances with particular and distinct biological activity 634:735 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 17 2 theme classifier 2526:2535 arg1 methods 2537:2543 These classifier methods 2520:2543 These classifier methods 2520:2543 These classifier methods are compared on the basis of their execution time and classification accuracy. 36781010 5 3 theme distinct 708:715 arg1 activity 728:735 distinct biological activity 708:735 distinct biological activity 708:735 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 7 4 theme anti-inflammatory 1145:1161 arg1 properties 1200:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 16 5 dep predict 2435:2441 arg1 albumin 2505:2511 albumin 2505:2511 albumin (ALB) 2505:2517 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 16 5 dep predict 2435:2441 arg1 bilirubin 2464:2472 direct bilirubin 2457:2472 direct bilirubin (DB) 2457:2477 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 16 5 dep predict 2435:2441 arg1 proteins 2486:2493 total proteins 2480:2493 total proteins (TP) 2480:2498 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 16 5 dep predict 2435:2441 arg1 TP 2496:2497 TP 2496:2497 TP 2496:2497 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 16 5 dep predict 2435:2441 arg1 ALB 2514:2516 ALB 2514:2516 ALB 2514:2516 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 16 5 dep predict 2435:2441 arg1 DB 2475:2476 DB 2475:2476 DB 2475:2476 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 16 5 dep predict 2435:2441 arg1 age 2452:2454 age 2452:2454 age 2452:2454 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 8 6 theme experimental 1221:1232 arg1 model 1234:1238 an experimental model 1218:1238 an experimental model 1218:1238 Using an experimental model, the current research intends to collect data on the therapeutic value of macroalgae nanoparticles for fatty liver disease. 36781010 11 7 theme regression 1669:1678 arg1 models 1650:1655 two models 1646:1655 two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence 1646:1774 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 7 8 theme antitumoral 1132:1142 arg1 properties 1200:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 2 9 theme long-term 239:247 arg1 exposure 249:256 long-term exposure 239:256 long-term exposure to harmful substances, medicines, and microorganisms 239:309 Liver fibrosis may be brought on by long-term exposure to harmful substances, medicines, and microorganisms. 36781010 1 10 theme issues 153:158 arg1 issues 153:158 the major health issues 136:158 the major health issues facing people worldwide 136:182 One of the major health issues facing people worldwide is liver fibrosis. 36781010 1 10 theme issues 153:158 arg1 One 129:131 One 129:131 One 129:131 One of the major health issues facing people worldwide is liver fibrosis. 36781010 8 11 theme therapeutic 1293:1303 arg1 value 1305:1309 the therapeutic value 1289:1309 the therapeutic value of macroalgae nanoparticles for fatty liver disease 1289:1361 Using an experimental model, the current research intends to collect data on the therapeutic value of macroalgae nanoparticles for fatty liver disease. 36781010 7 12 theme antidiabetic 1118:1129 arg1 properties 1200:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 6 13 theme diverse 799:805 arg1 cases 814:818 diverse marine cases 799:818 diverse marine cases 799:818 Macroalgae in diverse marine cases offer a few biologically active metabolites, comprising sterols, polyunsaturated fatty acids, carotenoids, oligosaccharides, polysaccharides, proteins, polyphenols, vitamins, and minerals. 36781010 1 14 theme people 167:172 arg1 worldwide 174:182 people worldwide 167:182 people worldwide 167:182 One of the major health issues facing people worldwide is liver fibrosis. 36781010 8 15 theme current 1245:1251 arg1 research 1253:1260 the current research 1241:1260 the current research 1241:1260 Using an experimental model, the current research intends to collect data on the therapeutic value of macroalgae nanoparticles for fatty liver disease. 36781010 7 16 theme antimicrobial 1103:1115 arg1 properties 1200:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 8 17 theme nanoparticles 1325:1337 arg1 value 1305:1309 the therapeutic value 1289:1309 the therapeutic value of macroalgae nanoparticles for fatty liver disease 1289:1361 Using an experimental model, the current research intends to collect data on the therapeutic value of macroalgae nanoparticles for fatty liver disease. 36781010 5 18 theme activity 728:735 arg1 Macroalgae 619:628 Macroalgae 619:628 Macroalgae 619:628 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 5 18 theme activity 728:735 arg1 sources 656:662 potentially excellent sources 634:662 potentially excellent sources of bioactive substances with particular and distinct biological activity 634:735 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 7 19 theme antiangiogenic 1164:1177 arg1 properties 1200:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 8 20 theme fatty 1343:1347 arg1 disease 1355:1361 fatty liver disease 1343:1361 fatty liver disease 1343:1361 Using an experimental model, the current research intends to collect data on the therapeutic value of macroalgae nanoparticles for fatty liver disease. 36781010 14 21 theme algal 2120:2124 arg1 extracts 2126:2133 algal extracts 2120:2133 algal extracts 2120:2133 In addition to improving kidney function (urea and creatinine), algal extracts enhance fat metabolism (triglycerides and cholesterol). 36781010 5 22 theme substances 677:686 arg1 Macroalgae 619:628 Macroalgae 619:628 Macroalgae 619:628 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 5 22 theme substances 677:686 arg1 sources 656:662 potentially excellent sources 634:662 potentially excellent sources of bioactive substances with particular and distinct biological activity 634:735 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 7 23 from interest 1037:1044 arg1 potential 1060:1068 their high potential 1049:1068 their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1049:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 14 24 dep improving 2071:2079 arg1 addition 2059:2066 addition 2059:2066 addition 2059:2066 In addition to improving kidney function (urea and creatinine), algal extracts enhance fat metabolism (triglycerides and cholesterol). 36781010 7 25 theme great 1031:1035 arg1 interest 1037:1044 great interest 1031:1044 great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1031:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 15 26 theme type 2273:2276 arg1 error 2280:2284 a type I error 2271:2284 a type I error of 9.1% 2271:2292 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 26 theme type 2273:2276 arg1 % 2220:2220 70.2% 2216:2220 70.2% 2216:2220 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 27 theme accuracy 2199:2206 arg1 rate 2208:2211 an accuracy rate 2196:2211 an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0% 2196:2322 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 13 28 theme phosphatases 1933:1944 arg1 concentrations 1887:1900 the high blood concentrations 1872:1900 the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases 1872:1972 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 0 29 theme fatty 54:58 arg1 disease 66:72 fatty liver disease 54:72 fatty liver disease 54:72 Effect of nanoparticle macroalgae in the treatment of fatty liver disease using logistic regression, and support vector machine. 36781010 15 30 theme % 2322:2322 arg1 error 2280:2284 a type I error 2271:2284 a type I error of 9.1% 2271:2292 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 30 theme % 2322:2322 arg1 specificity 2249:2259 a specificity 2247:2259 a specificity of 74.7% 2247:2268 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 30 theme % 2322:2322 arg1 error 2309:2313 a type II error 2299:2313 a type II error of 21.0% 2299:2322 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 30 theme % 2322:2322 arg1 % 2220:2220 70.2% 2216:2220 70.2% 2216:2220 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 30 theme % 2322:2322 arg1 sensitivity 2225:2235 a sensitivity 2223:2235 a sensitivity of 92.3% 2223:2244 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 7 31 theme high 1055:1058 arg1 potential 1060:1068 their high potential 1049:1068 their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1049:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 13 32 theme blood 1881:1885 arg1 concentrations 1887:1900 the high blood concentrations 1872:1900 the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases 1872:1972 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 11 33 theme incidence 1766:1774 arg1 likelihood 1738:1747 the likelihood 1734:1747 the likelihood of liver disease incidence 1734:1774 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 0 34 theme disease 66:72 arg1 treatment 41:49 the treatment 37:49 the treatment of fatty liver disease 37:72 Effect of nanoparticle macroalgae in the treatment of fatty liver disease using logistic regression, and support vector machine. 36781010 1 35 theme major 140:144 arg1 issues 153:158 the major health issues 136:158 the major health issues facing people worldwide 136:182 One of the major health issues facing people worldwide is liver fibrosis. 36781010 0 36 from Effect 0:5 arg1 treatment 41:49 the treatment 37:49 the treatment of fatty liver disease 37:72 Effect of nanoparticle macroalgae in the treatment of fatty liver disease using logistic regression, and support vector machine. 36781010 10 37 theme research 1486:1493 arg1 purpose 1470:1476 The purpose 1466:1476 The purpose of this research 1466:1493 The purpose of this research is to assess the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4). 36781010 11 38 theme liver 1752:1756 arg1 incidence 1766:1774 liver disease incidence 1752:1774 liver disease incidence 1752:1774 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 0 39 theme logistic 80:87 arg1 regression 89:98 logistic regression 80:98 logistic regression 80:98 Effect of nanoparticle macroalgae in the treatment of fatty liver disease using logistic regression, and support vector machine. 36781010 13 40 theme serum 2032:2036 arg1 levels 2048:2053 serum bilirubin levels 2032:2053 serum bilirubin levels 2032:2053 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 3 41 theme algae 319:323 arg1 species 325:331 Marine algae species 312:331 Marine algae species 312:331 Marine algae species have provided a biological variety in the research phase of novel approaches to the treatment of numerous ailments. 36781010 3 42 from variety 360:366 arg1 phase 384:388 the research phase 371:388 the research phase of novel approaches to the treatment of numerous ailments 371:446 Marine algae species have provided a biological variety in the research phase of novel approaches to the treatment of numerous ailments. 36781010 0 43 theme liver 60:64 arg1 disease 66:72 fatty liver disease 54:72 fatty liver disease 54:72 Effect of nanoparticle macroalgae in the treatment of fatty liver disease using logistic regression, and support vector machine. 36781010 3 44 theme novel 393:397 arg1 approaches 399:408 novel approaches 393:408 novel approaches to the treatment of numerous ailments 393:446 Marine algae species have provided a biological variety in the research phase of novel approaches to the treatment of numerous ailments. 36781010 13 45 dep considerable 1996:2007 arg1 p < 0.05 2010:2017 p < 0.05 2010:2017 p < 0.05 2010:2017 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 5 46 with substances 677:686 arg1 particular 693:702 particular 693:702 particular 693:702 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 17 47 theme time 2590:2593 arg1 basis 2565:2569 the basis 2561:2569 the basis of their execution time and classification accuracy 2561:2621 These classifier methods are compared on the basis of their execution time and classification accuracy. 36781010 3 48 theme numerous 430:437 arg1 ailments 439:446 numerous ailments 430:446 numerous ailments 430:446 Marine algae species have provided a biological variety in the research phase of novel approaches to the treatment of numerous ailments. 36781010 0 49 theme nanoparticle 10:21 arg1 macroalgae 23:32 nanoparticle macroalgae 10:32 nanoparticle macroalgae 10:32 Effect of nanoparticle macroalgae in the treatment of fatty liver disease using logistic regression, and support vector machine. 36781010 9 50 theme predicting 1389:1398 arg1 illnesses 1400:1408 predicting illnesses 1389:1408 predicting illnesses from the extensive medical datasets 1389:1444 The researchers' goal of predicting illnesses from the extensive medical datasets is quite difficult. 36781010 6 51 theme fatty 901:905 arg1 acids 907:911 polyunsaturated fatty acids 885:911 polyunsaturated fatty acids 885:911 Macroalgae in diverse marine cases offer a few biologically active metabolites, comprising sterols, polyunsaturated fatty acids, carotenoids, oligosaccharides, polysaccharides, proteins, polyphenols, vitamins, and minerals. 36781010 5 52 with activity 728:735 arg1 particular 693:702 particular 693:702 particular 693:702 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 17 53 theme classification 2599:2612 arg1 accuracy 2614:2621 classification accuracy 2599:2621 classification accuracy 2599:2621 These classifier methods are compared on the basis of their execution time and classification accuracy. 36781010 4 54 theme bioactive 528:536 arg1 composition 547:557 their rich bioactive chemical composition 517:557 their rich bioactive chemical composition 517:557 Marine macroalgae have recently been the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals. 36781010 11 55 theme machines 1704:1711 arg1 models 1650:1655 two models 1646:1655 two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence 1646:1774 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 13 56 theme PP 1837:1838 arg1 macro-algae 1840:1850 PP macro-algae 1837:1850 PP macro-algae 1837:1850 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 17 57 theme accuracy 2614:2621 arg1 basis 2565:2569 the basis 2561:2569 the basis of their execution time and classification accuracy 2561:2621 These classifier methods are compared on the basis of their execution time and classification accuracy. 36781010 16 58 theme laboratory 2406:2415 arg1 tests 2417:2421 laboratory tests 2406:2421 laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB) 2406:2517 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 11 59 theme support 1689:1695 arg1 SVM 1714:1716 SVM 1714:1716 SVM 1714:1716 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 11 59 theme support 1689:1695 arg1 machines 1704:1711 support vector machines 1689:1711 support vector machines (SVM) 1689:1717 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 9 60 theme extensive 1419:1427 arg1 datasets 1437:1444 the extensive medical datasets 1415:1444 the extensive medical datasets 1415:1444 The researchers' goal of predicting illnesses from the extensive medical datasets is quite difficult. 36781010 15 61 theme excellent 2363:2371 arg1 performance 2373:2383 excellent performance 2363:2383 excellent performance 2363:2383 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 10 62 theme liver 1569:1573 arg1 fibrosis 1575:1582 liver fibrosis 1569:1582 liver fibrosis caused by carbon tetrachloride (CCl4) 1569:1620 The purpose of this research is to assess the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4). 36781010 11 63 theme logistic 1660:1667 arg1 LR 1681:1682 LR 1681:1682 LR 1681:1682 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 11 63 theme logistic 1660:1667 arg1 regression 1669:1678 logistic regression 1660:1678 logistic regression (LR) 1660:1683 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 10 64 theme carbon 1594:1599 arg1 CCl4 1616:1619 CCl4 1616:1619 CCl4 1616:1619 The purpose of this research is to assess the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4). 36781010 10 64 theme carbon 1594:1599 arg1 tetrachloride 1601:1613 carbon tetrachloride 1594:1613 carbon tetrachloride (CCl4) 1594:1620 The purpose of this research is to assess the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4). 36781010 6 65 theme few 828:830 arg1 metabolites 852:862 a few biologically active metabolites 826:862 a few biologically active metabolites 826:862 Macroalgae in diverse marine cases offer a few biologically active metabolites, comprising sterols, polyunsaturated fatty acids, carotenoids, oligosaccharides, polysaccharides, proteins, polyphenols, vitamins, and minerals. 36781010 2 66 theme harmful 261:267 arg1 substances 269:278 harmful substances 261:278 harmful substances 261:278 Liver fibrosis may be brought on by long-term exposure to harmful substances, medicines, and microorganisms. 36781010 1 67 theme health 146:151 arg1 issues 153:158 the major health issues 136:158 the major health issues facing people worldwide 136:182 One of the major health issues facing people worldwide is liver fibrosis. 36781010 3 68 theme research 375:382 arg1 phase 384:388 the research phase 371:388 the research phase of novel approaches to the treatment of numerous ailments 371:446 Marine algae species have provided a biological variety in the research phase of novel approaches to the treatment of numerous ailments. 36781010 6 69 theme marine 807:812 arg1 cases 814:818 diverse marine cases 799:818 diverse marine cases 799:818 Macroalgae in diverse marine cases offer a few biologically active metabolites, comprising sterols, polyunsaturated fatty acids, carotenoids, oligosaccharides, polysaccharides, proteins, polyphenols, vitamins, and minerals. 36781010 13 70 theme lactate 1951:1957 arg1 dehydrogenases 1959:1972 lactate dehydrogenases 1951:1972 lactate dehydrogenases 1951:1972 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 0 71 theme vector 113:118 arg1 machine 120:126 support vector machine 105:126 support vector machine 105:126 Effect of nanoparticle macroalgae in the treatment of fatty liver disease using logistic regression, and support vector machine. 36781010 13 72 theme dehydrogenases 1959:1972 arg1 concentrations 1887:1900 the high blood concentrations 1872:1900 the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases 1872:1972 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 13 73 from decrease 2020:2027 arg1 levels 2048:2053 serum bilirubin levels 2032:2053 serum bilirubin levels 2032:2053 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 16 74 theme total 2480:2484 arg1 TP 2496:2497 TP 2496:2497 TP 2496:2497 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 16 74 theme total 2480:2484 arg1 proteins 2486:2493 total proteins 2480:2493 total proteins (TP) 2480:2498 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 17 75 theme execution 2580:2588 arg1 time 2590:2593 execution time 2580:2593 execution time 2580:2593 These classifier methods are compared on the basis of their execution time and classification accuracy. 36781010 4 76 theme nutraceuticals 603:616 arg1 production 581:590 the production 577:590 the production of various nutraceuticals 577:616 Marine macroalgae have recently been the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals. 36781010 14 77 theme fat 2143:2145 arg1 metabolism 2147:2156 fat metabolism 2143:2156 fat metabolism (triglycerides and cholesterol) 2143:2188 In addition to improving kidney function (urea and creatinine), algal extracts enhance fat metabolism (triglycerides and cholesterol). 36781010 7 78 theme supporting 1074:1083 arg1 properties 1200:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 1 79 theme liver 187:191 arg1 fibrosis 193:200 liver fibrosis 187:200 liver fibrosis 187:200 One of the major health issues facing people worldwide is liver fibrosis. 36781010 8 80 theme macroalgae 1314:1323 arg1 nanoparticles 1325:1337 macroalgae nanoparticles 1314:1337 macroalgae nanoparticles 1314:1337 Using an experimental model, the current research intends to collect data on the therapeutic value of macroalgae nanoparticles for fatty liver disease. 36781010 5 81 theme bioactive 667:675 arg1 substances 677:686 bioactive substances 667:686 bioactive substances with particular 667:702 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 15 82 theme % 2292:2292 arg1 error 2280:2284 a type I error 2271:2284 a type I error of 9.1% 2271:2292 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 82 theme % 2292:2292 arg1 specificity 2249:2259 a specificity 2247:2259 a specificity of 74.7% 2247:2268 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 82 theme % 2292:2292 arg1 error 2309:2313 a type II error 2299:2313 a type II error of 21.0% 2299:2322 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 82 theme % 2292:2292 arg1 % 2220:2220 70.2% 2216:2220 70.2% 2216:2220 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 82 theme % 2292:2292 arg1 sensitivity 2225:2235 a sensitivity 2223:2235 a sensitivity of 92.3% 2223:2244 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 2 83 theme Liver 203:207 arg1 fibrosis 209:216 Liver fibrosis 203:216 Liver fibrosis 203:216 Liver fibrosis may be brought on by long-term exposure to harmful substances, medicines, and microorganisms. 36781010 10 84 from effects 1523:1529 arg1 fibrosis 1575:1582 liver fibrosis 1569:1582 liver fibrosis caused by carbon tetrachloride (CCl4) 1569:1620 The purpose of this research is to assess the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4). 36781010 13 85 theme aminotransferases 1905:1921 arg1 concentrations 1887:1900 the high blood concentrations 1872:1900 the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases 1872:1972 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 8 86 from data 1281:1284 arg1 value 1305:1309 the therapeutic value 1289:1309 the therapeutic value of macroalgae nanoparticles for fatty liver disease 1289:1361 Using an experimental model, the current research intends to collect data on the therapeutic value of macroalgae nanoparticles for fatty liver disease. 36781010 8 87 theme liver 1349:1353 arg1 disease 1355:1361 fatty liver disease 1343:1361 fatty liver disease 1343:1361 Using an experimental model, the current research intends to collect data on the therapeutic value of macroalgae nanoparticles for fatty liver disease. 36781010 13 88 theme alkaline 1924:1931 arg1 phosphatases 1933:1944 alkaline phosphatases 1924:1944 alkaline phosphatases 1924:1944 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 5 89 theme terrestrial 760:770 arg1 equivalents 772:782 their terrestrial equivalents 754:782 their terrestrial equivalents 754:782 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 15 90 theme I 2278:2278 arg1 error 2280:2284 a type I error 2271:2284 a type I error of 9.1% 2271:2292 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 90 theme I 2278:2278 arg1 % 2220:2220 70.2% 2216:2220 70.2% 2216:2220 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 3 91 theme Marine 312:317 arg1 species 325:331 Marine algae species 312:331 Marine algae species 312:331 Marine algae species have provided a biological variety in the research phase of novel approaches to the treatment of numerous ailments. 36781010 13 92 theme high 1876:1879 arg1 concentrations 1887:1900 the high blood concentrations 1872:1900 the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases 1872:1972 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 15 93 theme predictive 2329:2338 arg1 model 2340:2344 the predictive model 2325:2344 the predictive model 2325:2344 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 16 94 theme direct 2457:2462 arg1 DB 2475:2476 DB 2475:2476 DB 2475:2476 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 16 94 theme direct 2457:2462 arg1 bilirubin 2464:2472 direct bilirubin 2457:2472 direct bilirubin (DB) 2457:2477 The model validated laboratory tests' ability to predict illness (age; direct bilirubin (DB), total proteins (TP), and albumin (ALB). 36781010 0 95 theme support 105:111 arg1 machine 120:126 support vector machine 105:126 support vector machine 105:126 Effect of nanoparticle macroalgae in the treatment of fatty liver disease using logistic regression, and support vector machine. 36781010 4 96 theme Marine 449:454 arg1 macroalgae 456:465 Marine macroalgae 449:465 Marine macroalgae 449:465 Marine macroalgae have recently been the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals. 36781010 4 96 theme Marine 449:454 arg1 subject 490:496 the subject 486:496 the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals 486:616 Marine macroalgae have recently been the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals. 36781010 11 97 theme disease 1758:1764 arg1 incidence 1766:1774 liver disease incidence 1752:1774 liver disease incidence 1752:1774 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 13 98 theme bilirubin 2038:2046 arg1 levels 2048:2053 serum bilirubin levels 2032:2053 serum bilirubin levels 2032:2053 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 10 99 theme protective 1512:1521 arg1 effects 1523:1529 the protective effects 1508:1529 the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4) 1508:1620 The purpose of this research is to assess the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4). 36781010 15 100 theme type 2301:2304 arg1 error 2309:2313 a type II error 2299:2313 a type II error of 21.0% 2299:2322 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 100 theme type 2301:2304 arg1 % 2220:2220 70.2% 2216:2220 70.2% 2216:2220 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 9 101 from goal 1381:1384 arg1 datasets 1437:1444 the extensive medical datasets 1415:1444 the extensive medical datasets 1415:1444 The researchers' goal of predicting illnesses from the extensive medical datasets is quite difficult. 36781010 15 102 theme % 2220:2220 arg1 rate 2208:2211 an accuracy rate 2196:2211 an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0% 2196:2322 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 5 103 theme biological 717:726 arg1 activity 728:735 distinct biological activity 708:735 distinct biological activity 708:735 Macroalgae are potentially excellent sources of bioactive substances with particular and distinct biological activity when compared to their terrestrial equivalents. 36781010 4 104 theme rich 523:526 arg1 composition 547:557 their rich bioactive chemical composition 517:557 their rich bioactive chemical composition 517:557 Marine macroalgae have recently been the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals. 36781010 14 105 theme kidney 2081:2086 arg1 function 2088:2095 kidney function 2081:2095 kidney function (urea and creatinine) 2081:2117 In addition to improving kidney function (urea and creatinine), algal extracts enhance fat metabolism (triglycerides and cholesterol). 36781010 3 106 theme approaches 399:408 arg1 phase 384:388 the research phase 371:388 the research phase of novel approaches to the treatment of numerous ailments 371:446 Marine algae species have provided a biological variety in the research phase of novel approaches to the treatment of numerous ailments. 36781010 0 107 theme macroalgae 23:32 arg1 Effect 0:5 Effect 0:5 Effect of nanoparticle macroalgae in the treatment of fatty liver disease 0:72 Effect of nanoparticle macroalgae in the treatment of fatty liver disease using logistic regression, and support vector machine. 36781010 15 108 theme % 2244:2244 arg1 error 2280:2284 a type I error 2271:2284 a type I error of 9.1% 2271:2292 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 108 theme % 2244:2244 arg1 specificity 2249:2259 a specificity 2247:2259 a specificity of 74.7% 2247:2268 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 108 theme % 2244:2244 arg1 error 2309:2313 a type II error 2299:2313 a type II error of 21.0% 2299:2322 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 108 theme % 2244:2244 arg1 % 2220:2220 70.2% 2216:2220 70.2% 2216:2220 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 108 theme % 2244:2244 arg1 sensitivity 2225:2235 a sensitivity 2223:2235 a sensitivity of 92.3% 2223:2244 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 3 109 theme biological 349:358 arg1 variety 360:366 a biological variety 347:366 a biological variety in the research phase of novel approaches to the treatment of numerous ailments 347:446 Marine algae species have provided a biological variety in the research phase of novel approaches to the treatment of numerous ailments. 36781010 4 110 theme chemical 538:545 arg1 composition 547:557 their rich bioactive chemical composition 517:557 their rich bioactive chemical composition 517:557 Marine macroalgae have recently been the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals. 36781010 10 111 theme seaweed 1536:1542 arg1 effects 1523:1529 the protective effects 1508:1529 the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4) 1508:1620 The purpose of this research is to assess the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4). 36781010 11 112 theme vector 1697:1702 arg1 SVM 1714:1716 SVM 1714:1716 SVM 1714:1716 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 11 112 theme vector 1697:1702 arg1 machines 1704:1711 support vector machines 1689:1711 support vector machines (SVM) 1689:1717 This research presents two models of logistic regression (LR) and support vector machines (SVM) for predicting the likelihood of liver disease incidence. 36781010 3 113 theme ailments 439:446 arg1 treatment 417:425 the treatment 413:425 the treatment of numerous ailments 413:446 Marine algae species have provided a biological variety in the research phase of novel approaches to the treatment of numerous ailments. 36781010 7 114 theme neuroprotective 1184:1198 arg1 properties 1200:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 9 115 theme illnesses 1400:1408 arg1 goal 1381:1384 The researchers' goal 1364:1384 The researchers' goal of predicting illnesses from the extensive medical datasets 1364:1444 The researchers' goal of predicting illnesses from the extensive medical datasets is quite difficult. 36781010 6 116 theme polyunsaturated 885:899 arg1 acids 907:911 polyunsaturated fatty acids 885:911 polyunsaturated fatty acids 885:911 Macroalgae in diverse marine cases offer a few biologically active metabolites, comprising sterols, polyunsaturated fatty acids, carotenoids, oligosaccharides, polysaccharides, proteins, polyphenols, vitamins, and minerals. 36781010 14 117 dep metabolism 2147:2156 arg1 cholesterol 2177:2187 cholesterol 2177:2187 cholesterol 2177:2187 In addition to improving kidney function (urea and creatinine), algal extracts enhance fat metabolism (triglycerides and cholesterol). 36781010 14 117 dep metabolism 2147:2156 arg1 triglycerides 2159:2171 triglycerides 2159:2171 triglycerides 2159:2171 In addition to improving kidney function (urea and creatinine), algal extracts enhance fat metabolism (triglycerides and cholesterol). 36781010 4 118 theme research 501:508 arg1 macroalgae 456:465 Marine macroalgae 449:465 Marine macroalgae 449:465 Marine macroalgae have recently been the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals. 36781010 4 118 theme research 501:508 arg1 subject 490:496 the subject 486:496 the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals 486:616 Marine macroalgae have recently been the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals. 36781010 12 119 theme model 1800:1804 arg1 performance 1781:1791 The performance 1777:1791 The performance of the model 1777:1804 The performance of the model was evaluated using a dataset. 36781010 7 120 theme immunomodulatory 1085:1100 arg1 properties 1200:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties 1074:1209 Accordingly, there is great interest in their high potential for supporting immunomodulatory, antimicrobial, antidiabetic, antitumoral, anti-inflammatory, antiangiogenic, and neuroprotective properties. 36781010 9 121 theme medical 1429:1435 arg1 datasets 1437:1444 the extensive medical datasets 1415:1444 the extensive medical datasets 1415:1444 The researchers' goal of predicting illnesses from the extensive medical datasets is quite difficult. 36781010 9 122 from datasets 1437:1444 arg1 goal 1381:1384 The researchers' goal 1364:1384 The researchers' goal of predicting illnesses from the extensive medical datasets 1364:1444 The researchers' goal of predicting illnesses from the extensive medical datasets is quite difficult. 36781010 9 122 from datasets 1437:1444 arg1 illnesses 1400:1408 predicting illnesses 1389:1408 predicting illnesses from the extensive medical datasets 1389:1444 The researchers' goal of predicting illnesses from the extensive medical datasets is quite difficult. 36781010 6 123 from Macroalgae 785:794 arg1 cases 814:818 diverse marine cases 799:818 diverse marine cases 799:818 Macroalgae in diverse marine cases offer a few biologically active metabolites, comprising sterols, polyunsaturated fatty acids, carotenoids, oligosaccharides, polysaccharides, proteins, polyphenols, vitamins, and minerals. 36781010 10 124 theme Padina 1545:1550 arg1 seaweed 1536:1542 seaweed 1536:1542 seaweed 1536:1542 The purpose of this research is to assess the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4). 36781010 10 124 theme Padina 1545:1550 arg1 pavonia 1552:1558 Padina pavonia 1545:1558 Padina pavonia (PP) 1545:1563 The purpose of this research is to assess the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4). 36781010 10 124 theme Padina 1545:1550 arg1 PP 1561:1562 PP 1561:1562 PP 1561:1562 The purpose of this research is to assess the protective effects of a seaweed, Padina pavonia (PP), on liver fibrosis caused by carbon tetrachloride (CCl4). 36781010 6 125 theme active 845:850 arg1 metabolites 852:862 a few biologically active metabolites 826:862 a few biologically active metabolites 826:862 Macroalgae in diverse marine cases offer a few biologically active metabolites, comprising sterols, polyunsaturated fatty acids, carotenoids, oligosaccharides, polysaccharides, proteins, polyphenols, vitamins, and minerals. 36781010 4 126 theme various 595:601 arg1 nutraceuticals 603:616 various nutraceuticals 595:616 various nutraceuticals 595:616 Marine macroalgae have recently been the subject of research due to their rich bioactive chemical composition and potential for the production of various nutraceuticals. 36781010 13 127 theme considerable 1996:2007 arg1 decrease 2020:2027 a considerable (p < 0.05) decrease 1994:2027 a considerable (p < 0.05) decrease in serum bilirubin levels 1994:2053 PP macro-algae considerably reduce the high blood concentrations of aminotransferases, alkaline phosphatases, and lactate dehydrogenases, as well as causing a considerable (p < 0.05) decrease in serum bilirubin levels. 36781010 15 128 theme % 2268:2268 arg1 error 2280:2284 a type I error 2271:2284 a type I error of 9.1% 2271:2292 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 128 theme % 2268:2268 arg1 specificity 2249:2259 a specificity 2247:2259 a specificity of 74.7% 2247:2268 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 128 theme % 2268:2268 arg1 error 2309:2313 a type II error 2299:2313 a type II error of 21.0% 2299:2322 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 128 theme % 2268:2268 arg1 % 2220:2220 70.2% 2216:2220 70.2% 2216:2220 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36781010 15 128 theme % 2268:2268 arg1 sensitivity 2225:2235 a sensitivity 2223:2235 a sensitivity of 92.3% 2223:2244 With an accuracy rate of 70.2%, a sensitivity of 92.3%, a specificity of 74.7%, a type I error of 9.1%, and a type II error of 21.0%, the predictive model has demonstrated excellent performance. 36143745 7 0 theme cell 1184:1187 arg1 cycle 1189:1193 cell cycle 1184:1193 cell cycle 1184:1193 LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. 36143745 4 1 theme tissue 831:836 arg1 regeneration 838:849 muscle tissue regeneration 824:849 muscle tissue regeneration 824:849 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 5 2 theme microscopy 870:879 arg1 studies 910:916 Scanning electron microscopy imaging and light microscopy studies 852:916 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining 852:948 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. 36143745 5 3 theme light 893:897 arg1 microscopy 899:908 light microscopy 893:908 light microscopy 893:908 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. 36143745 4 4 theme muscle 824:829 arg1 regeneration 838:849 muscle tissue regeneration 824:849 muscle tissue regeneration 824:849 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 9 5 used used 1590:1593 arg2 conjugates 1538:1547 polysaccharide conjugates 1523:1547 polysaccharide conjugates with peptides 1 and 2 1523:1569 Overall, the results of the study suggested that polysaccharide conjugates with peptides 1 and 2 can be potentially used in regenerative medicine. 36143745 9 6 with conjugates 1538:1547 arg1 peptides 1554:1561 peptides 1 and 2 1554:1569 peptides 1554:1561 Overall, the results of the study suggested that polysaccharide conjugates with peptides 1 and 2 can be potentially used in regenerative medicine. 36143745 9 6 with conjugates 1538:1547 arg1 2 1569:1569 2 1569:1569 2 1569:1569 Overall, the results of the study suggested that polysaccharide conjugates with peptides 1 and 2 can be potentially used in regenerative medicine. 36143745 0 7 theme Tissue 101:106 arg1 Regeneration 108:119 Muscle Tissue Regeneration 94:119 Muscle Tissue Regeneration 94:119 Evaluation of Polysaccharide-Peptide Conjugates Containing the RGD Motif for Potential Use in Muscle Tissue Regeneration. 36143745 4 8 theme calcium 745:751 arg1 alginate 753:760 calcium alginate 745:760 calcium alginate 745:760 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 5 9 theme peptide-polysaccharide 1012:1033 arg1 conjugates 1035:1044 the tested peptide-polysaccharide conjugates 1001:1044 the tested peptide-polysaccharide conjugates 1001:1044 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. 36143745 5 10 theme electron 861:868 arg1 microscopy 870:879 Scanning electron microscopy 852:879 Scanning electron microscopy imaging 852:887 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. 36143745 0 11 theme Muscle 94:99 arg1 Regeneration 108:119 Muscle Tissue Regeneration 94:119 Muscle Tissue Regeneration 94:119 Evaluation of Polysaccharide-Peptide Conjugates Containing the RGD Motif for Potential Use in Muscle Tissue Regeneration. 36143745 6 12 theme polysaccharide 1132:1145 arg1 matrix 1147:1152 the polysaccharide matrix 1128:1152 the polysaccharide matrix 1128:1152 The release factor (Q) varied depending on both the peptide and the structure of the polysaccharide matrix. 36143745 4 13 theme regeneration 838:849 arg1 supportive 810:819 supportive 810:819 supportive 810:819 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 4 13 theme regeneration 838:849 arg1 material 787:794 the ternary nonwoven material 766:794 the ternary nonwoven material 766:794 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 4 13 theme regeneration 838:849 arg1 conjugates 723:732 the conjugates 719:732 the conjugates containing calcium alginate 719:760 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 5 14 theme C2C12 962:966 arg1 cells 968:972 C2C12 cells 962:972 C2C12 cells 962:972 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. 36143745 4 15 theme Ki-67 687:691 arg1 assays 693:698 MTT and Ki-67 assays 679:698 MTT and Ki-67 assays 679:698 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 3 16 from application 617:627 arg1 medicine 645:652 regenerative medicine 632:652 regenerative medicine 632:652 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 1 17 theme New 122:124 arg1 materials 135:143 New scaffold materials 122:143 New scaffold materials composed of biodegradable components 122:180 New scaffold materials composed of biodegradable components are of great interest in regenerative medicine. 36143745 6 18 theme release 1051:1057 arg1 Q 1067:1067 Q 1067:1067 Q 1067:1067 The release factor (Q) varied depending on both the peptide and the structure of the polysaccharide matrix. 36143745 6 18 theme release 1051:1057 arg1 factor 1059:1064 The release factor 1047:1064 The release factor (Q) 1047:1068 The release factor (Q) varied depending on both the peptide and the structure of the polysaccharide matrix. 36143745 8 19 theme polysaccharide 1335:1348 arg1 nonwoven 1350:1357 the ternary polysaccharide nonwoven 1323:1357 the ternary polysaccharide nonwoven with peptide 1 1323:1372 Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. 36143745 8 20 with nonwoven 1350:1357 arg1 peptide 1364:1370 peptide 1 1364:1372 peptide 1 1364:1372 Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. 36143745 7 21 theme Ki-67 1173:1177 arg1 assays 1195:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays 1155:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays 1155:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. 36143745 5 22 with studies 910:916 arg1 staining 941:948 hematoxylin-eosin staining 923:948 hematoxylin-eosin staining 923:948 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. 36143745 7 23 theme Alamarblue® 1160:1170 arg1 assays 1195:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays 1155:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays 1155:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. 36143745 1 24 theme great 189:193 arg1 interest 195:202 great interest 189:202 great interest 189:202 New scaffold materials composed of biodegradable components are of great interest in regenerative medicine. 36143745 7 25 theme cycle 1189:1193 arg1 assays 1195:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays 1155:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays 1155:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. 36143745 6 26 theme matrix 1147:1152 arg1 peptide 1099:1105 the peptide 1095:1105 the peptide 1095:1105 The release factor (Q) varied depending on both the peptide and the structure of the polysaccharide matrix. 36143745 6 26 theme matrix 1147:1152 arg1 structure 1115:1123 the structure 1111:1123 the structure of the polysaccharide matrix 1111:1152 The release factor (Q) varied depending on both the peptide and the structure of the polysaccharide matrix. 36143745 3 27 theme peptide-polysaccharide 404:425 arg1 conjugates 427:436 peptide-polysaccharide conjugates 404:436 peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds 404:567 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 5 28 theme hematoxylin-eosin 923:939 arg1 staining 941:948 hematoxylin-eosin staining 923:948 hematoxylin-eosin staining 923:948 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. 36143745 3 29 theme RGD 471:473 arg1 motif 475:479 RGD motif 471:479 RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) 471:534 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 29 theme RGD 471:473 arg1 scaffolds 559:567 scaffolds 559:567 scaffolds 559:567 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 29 theme RGD 471:473 arg1 polysaccharides 540:554 polysaccharides 540:554 polysaccharides 540:554 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 0 30 theme Conjugates 37:46 arg1 Evaluation 0:9 Evaluation 0:9 Evaluation of Polysaccharide-Peptide Conjugates 0:46 Evaluation of Polysaccharide-Peptide Conjugates Containing the RGD Motif for Potential Use in Muscle Tissue Regeneration. 36143745 8 31 contain containing 1299:1308 arg2 chitosan 1310:1317 chitosan 1310:1317 chitosan 1310:1317 Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. 36143745 8 31 contain containing 1299:1308 arg1 Conjugates 1288:1297 Conjugates 1288:1297 Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 1288:1372 Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. 36143745 8 31 contain containing 1299:1308 arg2 nonwoven 1350:1357 the ternary polysaccharide nonwoven 1323:1357 the ternary polysaccharide nonwoven with peptide 1 1323:1372 Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. 36143745 8 32 theme high 1389:1392 arg1 activity 1408:1415 very high antibacterial activity 1384:1415 very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae 1384:1471 Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. 36143745 1 33 theme regenerative 207:218 arg1 medicine 220:227 regenerative medicine 207:227 regenerative medicine 207:227 New scaffold materials composed of biodegradable components are of great interest in regenerative medicine. 36143745 0 34 theme Polysaccharide-Peptide 14:35 arg1 Conjugates 37:46 Polysaccharide-Peptide Conjugates 14:46 Polysaccharide-Peptide Conjugates 14:46 Evaluation of Polysaccharide-Peptide Conjugates Containing the RGD Motif for Potential Use in Muscle Tissue Regeneration. 36143745 9 35 theme study 1502:1506 arg1 results 1487:1493 the results 1483:1493 the results of the study 1483:1506 Overall, the results of the study suggested that polysaccharide conjugates with peptides 1 and 2 can be potentially used in regenerative medicine. 36143745 5 36 theme Scanning 852:859 arg1 microscopy 870:879 Scanning electron microscopy 852:879 Scanning electron microscopy imaging 852:887 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. 36143745 4 37 theme MTT 679:681 arg1 assays 693:698 MTT and Ki-67 assays 679:698 MTT and Ki-67 assays 679:698 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 0 38 from Use 87:89 arg1 Regeneration 108:119 Muscle Tissue Regeneration 94:119 Muscle Tissue Regeneration 94:119 Evaluation of Polysaccharide-Peptide Conjugates Containing the RGD Motif for Potential Use in Muscle Tissue Regeneration. 36143745 4 39 theme nonwoven 778:785 arg1 supportive 810:819 supportive 810:819 supportive 810:819 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 4 39 theme nonwoven 778:785 arg1 conjugates 723:732 the conjugates 719:732 the conjugates containing calcium alginate 719:760 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 4 39 theme nonwoven 778:785 arg1 material 787:794 the ternary nonwoven material 766:794 the ternary nonwoven material 766:794 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 7 40 dep peptides 1217:1224 arg1 1 1226:1226 1 1226:1226 1 1226:1226 LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. 36143745 7 40 dep peptides 1217:1224 arg1 2 1232:1232 2 1232:1232 2 1232:1232 LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. 36143745 3 41 attach derived 438:444 arg2 conjugates 427:436 peptide-polysaccharide conjugates 404:436 peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds 404:567 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 41 attach derived 438:444 arg1 peptides 451:458 peptides 451:458 peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds 451:567 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 4 42 theme ternary 770:776 arg1 supportive 810:819 supportive 810:819 supportive 810:819 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 4 42 theme ternary 770:776 arg1 conjugates 723:732 the conjugates 719:732 the conjugates containing calcium alginate 719:760 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 4 42 theme ternary 770:776 arg1 material 787:794 the ternary nonwoven material 766:794 the ternary nonwoven material 766:794 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 7 43 theme best 1260:1263 arg1 properties 1276:1285 the best biological properties 1256:1285 the best biological properties 1256:1285 LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. 36143745 4 44 contain containing 734:743 arg1 supportive 810:819 supportive 810:819 supportive 810:819 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 4 44 contain containing 734:743 arg1 material 787:794 the ternary nonwoven material 766:794 the ternary nonwoven material 766:794 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 4 44 contain containing 734:743 arg1 conjugates 723:732 the conjugates 719:732 the conjugates containing calcium alginate 719:760 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 4 44 contain containing 734:743 arg2 alginate 753:760 calcium alginate 745:760 calcium alginate 745:760 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 9 45 theme polysaccharide 1523:1536 arg1 conjugates 1538:1547 polysaccharide conjugates 1523:1547 polysaccharide conjugates with peptides 1 and 2 1523:1569 Overall, the results of the study suggested that polysaccharide conjugates with peptides 1 and 2 can be potentially used in regenerative medicine. 36143745 3 46 dep motif 475:479 arg1 3 532:532 3 532:532 3 532:532 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 46 dep motif 475:479 arg1 RGDfC 524:528 RGDfC 524:528 RGDfC 524:528 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 46 dep motif 475:479 arg1 H-GRGDS-NH2 497:507 H-GRGDS-NH2 (2) 497:511 H-GRGDS-NH2 (2) 497:511 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 46 dep motif 475:479 arg1 H-RGDS-OH 482:490 H-RGDS-OH (1) 482:494 H-RGDS-OH (1) 482:494 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 46 dep motif 475:479 arg1 cyclo 518:522 cyclo 518:522 cyclo(RGDfC) (3) 518:533 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 2 47 theme biodegradable 342:354 arg1 substances 380:389 biodegradable and biologically active substances 342:389 biodegradable and biologically active substances 342:389 These materials should be: stable, nontoxic, and biodegrade slowly and steadily, allowing the stable release of biodegradable and biologically active substances. 36143745 0 48 theme RGD 63:65 arg1 Motif 67:71 the RGD Motif 59:71 the RGD Motif for Potential Use in Muscle Tissue Regeneration 59:119 Evaluation of Polysaccharide-Peptide Conjugates Containing the RGD Motif for Potential Use in Muscle Tissue Regeneration. 36143745 8 49 theme antibacterial 1394:1406 arg1 activity 1408:1415 very high antibacterial activity 1384:1415 very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae 1384:1471 Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. 36143745 8 50 with chitosan 1310:1317 arg1 peptide 1364:1370 peptide 1 1364:1372 peptide 1 1364:1372 Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. 36143745 1 51 theme biodegradable 157:169 arg1 components 171:180 biodegradable components 157:180 biodegradable components 157:180 New scaffold materials composed of biodegradable components are of great interest in regenerative medicine. 36143745 1 52 theme scaffold 126:133 arg1 materials 135:143 New scaffold materials 122:143 New scaffold materials composed of biodegradable components 122:180 New scaffold materials composed of biodegradable components are of great interest in regenerative medicine. 36143745 3 53 contain containing 460:469 arg2 polysaccharides 540:554 polysaccharides 540:554 polysaccharides 540:554 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 53 contain containing 460:469 arg2 scaffolds 559:567 scaffolds 559:567 scaffolds 559:567 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 53 contain containing 460:469 arg2 motif 475:479 RGD motif 471:479 RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) 471:534 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 53 contain containing 460:469 arg1 peptides 451:458 peptides 451:458 peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds 451:567 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 5 54 theme tested 1005:1010 arg1 conjugates 1035:1044 the tested peptide-polysaccharide conjugates 1001:1044 the tested peptide-polysaccharide conjugates 1001:1044 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. 36143745 4 55 theme assays 693:698 arg1 results 668:674 the results 664:674 the results of MTT and Ki-67 assays 664:698 Based on the results of MTT and Ki-67 assays, we can state that the conjugates containing calcium alginate and the ternary nonwoven material were the most supportive of muscle tissue regeneration. 36143745 8 56 theme ternary 1327:1333 arg1 nonwoven 1350:1357 the ternary polysaccharide nonwoven 1323:1357 the ternary polysaccharide nonwoven with peptide 1 1323:1372 Conjugates containing chitosan and the ternary polysaccharide nonwoven with peptide 1 exhibited very high antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. 36143745 3 57 theme regenerative 632:643 arg1 medicine 645:652 regenerative medicine 632:652 regenerative medicine 632:652 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 3 58 theme appropriate 588:598 arg1 biomaterials 600:611 the most appropriate biomaterials 579:611 the most appropriate biomaterials for application in regenerative medicine 579:652 We analyzed peptide-polysaccharide conjugates derived from peptides containing RGD motif (H-RGDS-OH (1), H-GRGDS-NH2 (2), and cyclo(RGDfC) (3)) and polysaccharides as scaffolds to select the most appropriate biomaterials for application in regenerative medicine. 36143745 1 59 from interest 195:202 arg1 medicine 220:227 regenerative medicine 207:227 regenerative medicine 207:227 New scaffold materials composed of biodegradable components are of great interest in regenerative medicine. 36143745 2 60 theme stable 324:329 arg1 release 331:337 the stable release 320:337 the stable release of biodegradable and biologically active substances 320:389 These materials should be: stable, nontoxic, and biodegrade slowly and steadily, allowing the stable release of biodegradable and biologically active substances. 36143745 5 61 theme microscopy 899:908 arg1 studies 910:916 Scanning electron microscopy imaging and light microscopy studies 852:916 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining 852:948 Scanning electron microscopy imaging and light microscopy studies with hematoxylin-eosin staining showed that C2C12 cells were able to interact with the tested peptide-polysaccharide conjugates. 36143745 0 62 theme Potential 77:85 arg1 Use 87:89 Potential Use 77:89 Potential Use in Muscle Tissue Regeneration 77:119 Evaluation of Polysaccharide-Peptide Conjugates Containing the RGD Motif for Potential Use in Muscle Tissue Regeneration. 36143745 9 63 theme regenerative 1598:1609 arg1 medicine 1611:1618 regenerative medicine 1598:1618 regenerative medicine 1598:1618 Overall, the results of the study suggested that polysaccharide conjugates with peptides 1 and 2 can be potentially used in regenerative medicine. 36143745 7 64 theme biological 1265:1274 arg1 properties 1276:1285 the best biological properties 1256:1285 the best biological properties 1256:1285 LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. 36143745 2 65 theme substances 380:389 arg1 release 331:337 the stable release 320:337 the stable release of biodegradable and biologically active substances 320:389 These materials should be: stable, nontoxic, and biodegrade slowly and steadily, allowing the stable release of biodegradable and biologically active substances. 36143745 7 66 theme LDH 1155:1157 arg1 assays 1195:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays 1155:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays 1155:1200 LDH, Alamarblue®, Ki-67, and cell cycle assays indicated that peptides 1 and 2 were characterized by the best biological properties. 36143745 2 67 theme active 373:378 arg1 substances 380:389 biodegradable and biologically active substances 342:389 biodegradable and biologically active substances 342:389 These materials should be: stable, nontoxic, and biodegrade slowly and steadily, allowing the stable release of biodegradable and biologically active substances. 37065333 14 0 theme mean 2407:2410 arg1 age 2412:2414 The mean age 2403:2414 The mean age of the patients 2403:2430 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 14 0 theme mean 2407:2410 arg1 years 2448:2452 50.6 ± 13.9 years 2436:2452 50.6 ± 13.9 years 2436:2452 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 8 1 theme formulation 1700:1710 arg1 Clagen™ 1712:1718 the nutraceutical formulation Clagen™ 1682:1718 the nutraceutical formulation Clagen™ 1682:1718 The data were analyzed to evaluate the efficacy of the nutraceutical formulation Clagen™ in patients with OA of the knee. 37065333 22 2 theme long-term 3571:3579 arg1 studies 3581:3587 further long-term studies 3563:3587 further long-term studies with a comparison arm of NSAIDs 3563:3619 To validate these findings further long-term studies with a comparison arm of NSAIDs are needed. 37065333 17 3 theme [t 2873:2874 arg1 value 2854:2858 the goniometer value 2839:2858 the goniometer value of 7.3 ± 7.3 [t 2839:2874 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 4 4 theme shortest 856:863 arg1 time 865:868 the shortest time 852:868 the shortest time necessary 852:878 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 16 5 from reduction 2766:2774 arg1 pain 2779:2782 pain 2779:2782 pain at two months 2779:2796 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 16 5 from reduction 2766:2774 arg1 months 2791:2796 two months 2787:2796 two months 2787:2796 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 0 6 theme CurQlife 159:166 arg1 Nutraceuticals 179:192 Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals 131:192 Nutraceuticals 179:192 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 0 6 theme CurQlife 159:166 arg1 Curcumin 169:176 Curcumin 169:176 Curcumin 169:176 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 1 7 theme Background 249:258 arg1 Treatment 260:268 Background Treatment 249:268 Background Treatment of pain and inflammation 249:293 Background Treatment of pain and inflammation form the mainstay of osteoarthritis (OA) management. 37065333 6 8 dep [Aflapin 1126:1133 arg1 collagen 1253:1260 collagen 1253:1260 collagen (>5%) 1253:1266 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 8 dep [Aflapin 1126:1133 arg1 acid 1210:1213 hyaluronic acid 1199:1213 hyaluronic acid (60-70%) 1199:1222 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 8 dep [Aflapin 1126:1133 arg1 % 1221:1221 60-70% 1216:1221 60-70% 1216:1221 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 8 dep [Aflapin 1126:1133 arg1 % 1245:1245 >10% 1242:1245 >10% 1242:1245 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 8 dep [Aflapin 1126:1133 arg1 % 1265:1265 >5% 1263:1265 >5% 1263:1265 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 8 dep [Aflapin 1126:1133 arg1  polysaccharides 1224:1239  polysaccharides 1224:1239  polysaccharides (>10%) 1224:1246 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 9 theme OA 1327:1328 arg1 patients 1330:1337 OA patients 1327:1337 OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs 1327:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 10 theme OA 1414:1415 arg1 management 1400:1409 the long-term management 1386:1409 the long-term management of OA instead of NSAIDs 1386:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 21 11 theme OA 3477:3478 arg1 patients 3480:3487 OA patients 3477:3487 OA patients 3477:3487 The combination not only improved the symptoms and quality of life but, in the light of future perspective, NSAIDs can be withdrawn in OA patients, considering their long-term negative effects. 37065333 16 12 from baseline 2674:2681 arg1 score 2665:2669 VAS pain score 2656:2669 VAS pain score at baseline and two months 2656:2696 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 16 12 from baseline 2674:2681 arg1 mean 2648:2651 the mean 2644:2651 the mean of VAS pain score at baseline and two months 2644:2696 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 4 13 theme NSAID 837:841 arg1 dose 843:846 the lowest effective NSAID dose 816:846 the lowest effective NSAID dose for the shortest time necessary 816:878 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 6 14 theme Boswellia 1136:1144 arg1 extract 1154:1160 Boswellia serrata extract 1136:1160 Boswellia serrata extract 1136:1160 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 14 theme Boswellia 1136:1144 arg1 [Aflapin 1126:1133 Clagen™ [Aflapin 1118:1133 Clagen™ [Aflapin (Boswellia serrata extract) 1118:1161 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 12 15 theme standard 2281:2288 arg1 deviation 2290:2298 standard deviation 2281:2298 standard deviation 2281:2298 The qualitative characteristics were described using absolute and relative frequencies, and the quantitative measures were described as summary measures (mean, standard deviation). 37065333 9 16 theme monthly 1948:1954 arg1 follow-up 1956:1964 monthly follow-up 1948:1964 monthly follow-up 1948:1964 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 22 17 with studies 3581:3587 arg1 NSAIDs 3614:3619 NSAIDs 3614:3619 NSAIDs 3614:3619 To validate these findings further long-term studies with a comparison arm of NSAIDs are needed. 37065333 22 17 with studies 3581:3587 arg1 arm 3607:3609 a comparison arm 3594:3609 a comparison arm of NSAIDs 3594:3619 To validate these findings further long-term studies with a comparison arm of NSAIDs are needed. 37065333 7 18 theme study 1610:1614 arg1 part 1598:1601 part 1598:1601 part of the study 1598:1614 Methodology In this retrospective observational study, a total of 300 patients were screened, of whom 100 OA patients who fulfilled the criteria and agreed to be part of the study were enrolled. 37065333 6 19 theme [Aflapin 1126:1133 arg1 efficacy 1106:1113 the efficacy 1102:1113 the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs 1102:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 11 20 theme % 2089:2089 arg1 level 2104:2108 a 5% significance level 2086:2108 a 5% significance level (p <0.05) 2086:2118 The tests were performed at a 5% significance level (p <0.05). 37065333 11 20 theme % 2089:2089 arg1 <0.05 2113:2117 p <0.05 2111:2117 p <0.05 2111:2117 The tests were performed at a 5% significance level (p <0.05). 37065333 20 21 theme Conclusions 3263:3273 arg1 Clagen™ 3275:3281 Conclusions Clagen™ 3263:3281 Conclusions Clagen™ 3263:3281 Conclusions Clagen™ exerted positive adjuvant effects in the management of OA. 37065333 0 22 theme Type 113:116 arg1 Collagen 120:127 Native Type 2 Collagen 106:127 Native Type 2 Collagen 106:127 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 18 23 from end 3071:3073 arg1 score 3049:3053 the composite KOOS score 3030:3053 the composite KOOS score by 10.8% at the end of two months 3030:3087 It was also observed that Clagen™ significantly improved the composite KOOS score by 10.8% at the end of two months. 37065333 7 24 theme patients 1506:1513 arg1 total 1493:1497 a total 1491:1497 a total of 300 patients 1491:1513 Methodology In this retrospective observational study, a total of 300 patients were screened, of whom 100 OA patients who fulfilled the criteria and agreed to be part of the study were enrolled. 37065333 6 25 theme hyaluronic 1199:1208 arg1 acid 1210:1213 hyaluronic acid 1199:1213 hyaluronic acid (60-70%) 1199:1222 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 25 theme hyaluronic 1199:1208 arg1 % 1221:1221 60-70% 1216:1221 60-70% 1216:1221 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 17 26 theme value 2854:2858 arg1 -10.0 2883:2887 -10.0 2883:2887 -10.0 2883:2887 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 17 26 theme value 2854:2858 arg1 mean 2831:2834 the mean 2827:2834 the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] 2827:2898 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 0 27 theme Collagen 120:127 arg1 Combination 81:91 a Novel Combination 73:91 a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals 73:192 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 3 28 theme increased 554:562 arg1 risk 564:567 increased risk 554:567 increased risk for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID-induced nephrotoxicity 554:696 However, this comes at a cost of increased risk for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID-induced nephrotoxicity. 37065333 16 29 from mean 2648:2651 arg1 baseline 2674:2681 baseline 2674:2681 baseline 2674:2681 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 16 29 from mean 2648:2651 arg1 months 2691:2696 two months 2687:2696 two months 2687:2696 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 4 30 theme necessary 870:878 arg1 time 865:868 the shortest time 852:868 the shortest time necessary 852:878 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 6 31 theme Mobilee 1190:1196 arg1 efficacy 1106:1113 the efficacy 1102:1113 the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs 1102:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 9 32 theme primary 1786:1792 arg1 outcomes 1794:1801 primary outcomes 1786:1801 primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) 1786:1929 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 17 33 theme 7.3 ± 2863:2867 arg1 [t 2873:2874 7.3 ± 7.3 [t 2863:2874 7.3 ± 7.3 [t 2863:2874 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 0 34 theme Mobilee 131:137 arg1 Combination 81:91 a Novel Combination 73:91 a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals 73:192 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 13 35 dep 99 2353:2354 arg1 females 2373:2379 35 females 2370:2379 35 females 2370:2379 Results Of the 100 patients enrolled in the study, 99 (64 males and 35 females) completed the study. 37065333 13 35 dep 99 2353:2354 arg1 males 2360:2364 64 males 2357:2364 64 males 2357:2364 Results Of the 100 patients enrolled in the study, 99 (64 males and 35 females) completed the study. 37065333 14 36 theme 24.5 ± 2488:2493 arg1 kg/m2 2499:2503 24.5 ± 3.5 kg/m2 2488:2503 24.5 ± 3.5 kg/m2 2488:2503 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 14 36 theme 24.5 ± 2488:2493 arg1 index 2478:2482 the mean body mass index 2459:2482 the mean body mass index 2459:2482 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 6 37 theme collagen 1179:1186 arg1 efficacy 1106:1113 the efficacy 1102:1113 the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs 1102:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 0 38 theme Hyaluronic 140:149 arg1 Mobilee 131:137 Mobilee 131:137 Mobilee 131:137 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 0 38 theme Hyaluronic 140:149 arg1 Acid 151:154 Hyaluronic Acid 140:154 Hyaluronic Acid 140:154 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 5 39 theme NSAIDs 1047:1052 arg1 properties 1025:1034 anti-inflammatory and analgesic properties 993:1034 anti-inflammatory and analgesic properties instead of NSAIDs 993:1052 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 3 40 theme adverse 582:588 arg1 effects 590:596 multiple adverse effects 573:596 multiple adverse effects 573:596 However, this comes at a cost of increased risk for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID-induced nephrotoxicity. 37065333 6 41 theme type 1172:1175 arg1 collagen 1179:1186 native type 2 collagen 1165:1186 native type 2 collagen 1165:1186 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 16 42 theme score 2665:2669 arg1 mean 2648:2651 the mean 2644:2651 the mean of VAS pain score at baseline and two months 2644:2696 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 7 43 theme retrospective 1456:1468 arg1 study 1484:1488 this retrospective observational study 1451:1488 this retrospective observational study 1451:1488 Methodology In this retrospective observational study, a total of 300 patients were screened, of whom 100 OA patients who fulfilled the criteria and agreed to be part of the study were enrolled. 37065333 9 44 theme Visual 1825:1830 arg1 VAS 1846:1848 VAS 1846:1848 VAS 1846:1848 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 44 theme Visual 1825:1830 arg1 Scale 1839:1843 the Visual Analog Scale 1821:1843 the Visual Analog Scale 1821:1843 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 17 45 theme significant 2924:2934 arg1 improvements 2936:2947 statistically significant improvements 2910:2947 statistically significant improvements in the range of motion 2910:2970 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 0 46 theme Novel 75:79 arg1 Combination 81:91 a Novel Combination 73:91 a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals 73:192 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 7 47 dep Methodology 1436:1446 arg1 study 1484:1488 this retrospective observational study 1451:1488 this retrospective observational study 1451:1488 Methodology In this retrospective observational study, a total of 300 patients were screened, of whom 100 OA patients who fulfilled the criteria and agreed to be part of the study were enrolled. 37065333 0 48 theme Symptomatic 201:211 arg1 Improvement 213:223 the Symptomatic Improvement 197:223 the Symptomatic Improvement of Knee Osteoarthritis 197:246 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 21 49 theme negative 3518:3525 arg1 effects 3527:3533 their long-term negative effects 3502:3533 their long-term negative effects 3502:3533 The combination not only improved the symptoms and quality of life but, in the light of future perspective, NSAIDs can be withdrawn in OA patients, considering their long-term negative effects. 37065333 18 50 theme KOOS 3044:3047 arg1 score 3049:3053 the composite KOOS score 3030:3053 the composite KOOS score by 10.8% at the end of two months 3030:3087 It was also observed that Clagen™ significantly improved the composite KOOS score by 10.8% at the end of two months. 37065333 22 51 theme NSAIDs 3614:3619 arg1 NSAIDs 3614:3619 NSAIDs 3614:3619 NSAIDs 3614:3619 To validate these findings further long-term studies with a comparison arm of NSAIDs are needed. 37065333 22 51 theme NSAIDs 3614:3619 arg1 arm 3607:3609 a comparison arm 3594:3609 a comparison arm of NSAIDs 3594:3619 To validate these findings further long-term studies with a comparison arm of NSAIDs are needed. 37065333 19 52 dep significant 3239:3249 arg1 < 3254:3254 p < 0.05 3252:3259 p < 0.05 3252:3259 Similarly, KOOS scores for Symptoms, Function, and Quality of Life showed improvements of 9.6%, 9.8%, and 7.8%, respectively, and were statistically significant (p < 0.05). 37065333 4 53 theme adverse 736:742 arg1 event 744:748 an adverse event 733:748 an adverse event 733:748 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 5 54 theme disease-modifying 934:950 arg1 DMOADs 974:979 DMOADs 974:979 DMOADs 974:979 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 5 54 theme disease-modifying 934:950 arg1 drugs 967:971 disease-modifying osteoarthritis drugs 934:971 disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs 934:1052 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 0 55 theme Osteoarthritis 233:246 arg1 Improvement 213:223 the Symptomatic Improvement 197:223 the Symptomatic Improvement of Knee Osteoarthritis 197:246 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 5 56 theme drugs 967:971 arg1 strategy 895:902 One potential strategy 881:902 One potential strategy to achieve this 881:918 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 5 56 theme drugs 967:971 arg1 use 927:929 the use 923:929 the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA 923:1077 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 7 57 theme OA 1542:1543 arg1 patients 1545:1552 100 OA patients 1538:1552 100 OA patients who fulfilled the criteria and agreed to be part of the study 1538:1614 Methodology In this retrospective observational study, a total of 300 patients were screened, of whom 100 OA patients who fulfilled the criteria and agreed to be part of the study were enrolled. 37065333 14 58 theme mean 2463:2466 arg1 kg/m2 2499:2503 24.5 ± 3.5 kg/m2 2488:2503 24.5 ± 3.5 kg/m2 2488:2503 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 14 58 theme mean 2463:2466 arg1 index 2478:2482 the mean body mass index 2459:2482 the mean body mass index 2459:2482 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 4 59 theme potential 715:723 arg1 risk 725:728 the potential risk 711:728 the potential risk of an adverse event 711:748 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 4 60 dep effective 827:835 arg1 lowest 820:825 lowest 820:825 lowest 820:825 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 8 61 theme nutraceutical 1686:1698 arg1 Clagen™ 1712:1718 the nutraceutical formulation Clagen™ 1682:1718 the nutraceutical formulation Clagen™ 1682:1718 The data were analyzed to evaluate the efficacy of the nutraceutical formulation Clagen™ in patients with OA of the knee. 37065333 2 62 theme inflammation-blocking 409:429 arg1 mechanism 431:439 their inflammation-blocking mechanism 403:439 their inflammation-blocking mechanism 403:439 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 12 63 theme quantitative 2217:2228 arg1 measures 2265:2272 summary measures 2257:2272 summary measures (mean, standard deviation) 2257:2299 The qualitative characteristics were described using absolute and relative frequencies, and the quantitative measures were described as summary measures (mean, standard deviation). 37065333 12 63 theme quantitative 2217:2228 arg1 measures 2230:2237 the quantitative measures 2213:2237 the quantitative measures 2213:2237 The qualitative characteristics were described using absolute and relative frequencies, and the quantitative measures were described as summary measures (mean, standard deviation). 37065333 0 64 theme Observational 16:28 arg1 Study 30:34 A Retrospective Observational Study 0:34 A Retrospective Observational Study 0:34 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 1 65 theme pain 273:276 arg1 Treatment 260:268 Background Treatment 249:268 Background Treatment of pain and inflammation 249:293 Background Treatment of pain and inflammation form the mainstay of osteoarthritis (OA) management. 37065333 2 66 theme effective 455:463 arg1 class 465:469 a highly effective class 446:469 a highly effective class of drugs for chronic pain and inflammation in OA 446:518 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 2 66 theme effective 455:463 arg1 drugs 380:384 Non-steroidal anti-inflammatory drugs 348:384 Non-steroidal anti-inflammatory drugs (NSAIDs) 348:393 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 21 67 dep combination 3346:3356 arg1 only 3362:3365 only 3362:3365 only 3362:3365 The combination not only improved the symptoms and quality of life but, in the light of future perspective, NSAIDs can be withdrawn in OA patients, considering their long-term negative effects. 37065333 9 68 theme motion 1867:1872 arg1 VAS 1846:1848 VAS 1846:1848 VAS 1846:1848 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 68 theme motion 1867:1872 arg1 Score 1918:1922 Osteoarthritis Outcome Score 1895:1922 Osteoarthritis Outcome Score (KOOS) 1895:1929 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 68 theme motion 1867:1872 arg1 score 1851:1855 score 1851:1855 score 1851:1855 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 68 theme motion 1867:1872 arg1 KOOS 1925:1928 KOOS 1925:1928 KOOS 1925:1928 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 68 theme motion 1867:1872 arg1 range 1858:1862 range 1858:1862 range of motion 1858:1872 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 68 theme motion 1867:1872 arg1 Injury 1884:1889 Knee Injury 1879:1889 Knee Injury 1879:1889 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 68 theme motion 1867:1872 arg1 Scale 1839:1843 the Visual Analog Scale 1821:1843 the Visual Analog Scale 1821:1843 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 17 69 theme p 2890:2890 arg1 < 2892:2892 p < 0.05 2890:2897 p < 0.05 2890:2897 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 20 70 theme adjuvant 3300:3307 arg1 effects 3309:3315 positive adjuvant effects 3291:3315 positive adjuvant effects 3291:3315 Conclusions Clagen™ exerted positive adjuvant effects in the management of OA. 37065333 1 71 theme inflammation 282:293 arg1 Treatment 260:268 Background Treatment 249:268 Background Treatment of pain and inflammation 249:293 Background Treatment of pain and inflammation form the mainstay of osteoarthritis (OA) management. 37065333 21 72 theme future 3430:3435 arg1 perspective 3437:3447 future perspective 3430:3447 future perspective 3430:3447 The combination not only improved the symptoms and quality of life but, in the light of future perspective, NSAIDs can be withdrawn in OA patients, considering their long-term negative effects. 37065333 14 73 theme ± 2441:2441 arg1 years 2448:2452 50.6 ± 13.9 years 2436:2452 50.6 ± 13.9 years 2436:2452 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 14 73 theme ± 2441:2441 arg1 age 2412:2414 The mean age 2403:2414 The mean age of the patients 2403:2430 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 19 74 theme p 3252:3252 arg1 < 3254:3254 p < 0.05 3252:3259 p < 0.05 3252:3259 Similarly, KOOS scores for Symptoms, Function, and Quality of Life showed improvements of 9.6%, 9.8%, and 7.8%, respectively, and were statistically significant (p < 0.05). 37065333 19 75 theme % 3199:3199 arg1 improvements 3164:3175 improvements 3164:3175 improvements of 9.6%, 9.8%, and 7.8%, respectively 3164:3213 Similarly, KOOS scores for Symptoms, Function, and Quality of Life showed improvements of 9.6%, 9.8%, and 7.8%, respectively, and were statistically significant (p < 0.05). 37065333 0 76 theme Synergistic 51:61 arg1 Effect 63:68 the Synergistic Effect 47:68 the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis 47:246 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 14 77 theme mass 2473:2476 arg1 kg/m2 2499:2503 24.5 ± 3.5 kg/m2 2488:2503 24.5 ± 3.5 kg/m2 2488:2503 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 14 77 theme mass 2473:2476 arg1 index 2478:2482 the mean body mass index 2459:2482 the mean body mass index 2459:2482 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 3 78 theme side 651:654 arg1 effects 656:662 cardiovascular side effects 636:662 cardiovascular side effects 636:662 However, this comes at a cost of increased risk for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID-induced nephrotoxicity. 37065333 4 79 theme regulatory 760:769 arg1 bodies 771:776 numerous regulatory bodies 751:776 numerous regulatory bodies 751:776 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 16 80 theme VAS 2656:2658 arg1 score 2665:2669 VAS pain score 2656:2669 VAS pain score at baseline and two months 2656:2696 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 16 81 from months 2791:2796 arg1 pain 2779:2782 pain 2779:2782 pain at two months 2779:2796 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 16 81 from months 2791:2796 arg1 reduction 2766:2774 a significant reduction 2752:2774 a significant reduction in pain at two months 2752:2796 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 11 82 theme significance 2091:2102 arg1 level 2104:2108 a 5% significance level 2086:2108 a 5% significance level (p <0.05) 2086:2118 The tests were performed at a 5% significance level (p <0.05). 37065333 11 82 theme significance 2091:2102 arg1 <0.05 2113:2117 p <0.05 2111:2117 p <0.05 2111:2117 The tests were performed at a 5% significance level (p <0.05). 37065333 15 83 from analysis 2522:2529 arg1 baseline 2556:2563 the baseline 2552:2563 the baseline to the two-month follow-up 2552:2590 The statistical analysis of the outcomes from the baseline to the two-month follow-up was analyzed using paired t-test. 37065333 16 84 dep = 2720:2720 arg1 18.2 2722:2725 18.2 2722:2725 18.2 2722:2725 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 9 85 theme Osteoarthritis 1895:1908 arg1 KOOS 1925:1928 KOOS 1925:1928 KOOS 1925:1928 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 85 theme Osteoarthritis 1895:1908 arg1 Score 1918:1922 Osteoarthritis Outcome Score 1895:1922 Osteoarthritis Outcome Score (KOOS) 1895:1929 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 17 86 dep -10.0 2883:2887 arg1 < 2892:2892 p < 0.05 2890:2897 p < 0.05 2890:2897 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 2 87 theme Non-steroidal 348:360 arg1 class 465:469 a highly effective class 446:469 a highly effective class of drugs for chronic pain and inflammation in OA 446:518 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 2 87 theme Non-steroidal 348:360 arg1 NSAIDs 387:392 NSAIDs 387:392 NSAIDs 387:392 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 2 87 theme Non-steroidal 348:360 arg1 drugs 380:384 Non-steroidal anti-inflammatory drugs 348:384 Non-steroidal anti-inflammatory drugs (NSAIDs) 348:393 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 16 88 theme significant 2754:2764 arg1 reduction 2766:2774 a significant reduction 2752:2774 a significant reduction in pain at two months 2752:2796 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 5 89 contain containing 982:991 arg2 properties 1025:1034 anti-inflammatory and analgesic properties 993:1034 anti-inflammatory and analgesic properties instead of NSAIDs 993:1052 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 5 89 contain containing 982:991 arg1 DMOADs 974:979 DMOADs 974:979 DMOADs 974:979 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 5 89 contain containing 982:991 arg1 drugs 967:971 disease-modifying osteoarthritis drugs 934:971 disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs 934:1052 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 3 90 theme NSAID-induced 669:681 arg1 nephrotoxicity 683:696 NSAID-induced nephrotoxicity 669:696 NSAID-induced nephrotoxicity 669:696 However, this comes at a cost of increased risk for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID-induced nephrotoxicity. 37065333 8 91 theme Clagen™ 1712:1718 arg1 efficacy 1670:1677 the efficacy 1666:1677 the efficacy of the nutraceutical formulation Clagen™ in patients with OA of the knee 1666:1750 The data were analyzed to evaluate the efficacy of the nutraceutical formulation Clagen™ in patients with OA of the knee. 37065333 19 92 theme % 3183:3183 arg1 improvements 3164:3175 improvements 3164:3175 improvements of 9.6%, 9.8%, and 7.8%, respectively 3164:3213 Similarly, KOOS scores for Symptoms, Function, and Quality of Life showed improvements of 9.6%, 9.8%, and 7.8%, respectively, and were statistically significant (p < 0.05). 37065333 12 93 theme qualitative 2125:2135 arg1 characteristics 2137:2151 The qualitative characteristics 2121:2151 The qualitative characteristics 2121:2151 The qualitative characteristics were described using absolute and relative frequencies, and the quantitative measures were described as summary measures (mean, standard deviation). 37065333 13 94 theme patients 2321:2328 arg1 Results 2302:2308 Results 2302:2308 Results Of the 100 patients enrolled in the study, 99 (64 males and 35 females) 2302:2380 Results Of the 100 patients enrolled in the study, 99 (64 males and 35 females) completed the study. 37065333 5 95 theme analgesic 1015:1023 arg1 properties 1025:1034 anti-inflammatory and analgesic properties 993:1034 anti-inflammatory and analgesic properties instead of NSAIDs 993:1052 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 12 96 dep mean 2275:2278 arg1 deviation 2290:2298 standard deviation 2281:2298 standard deviation 2281:2298 The qualitative characteristics were described using absolute and relative frequencies, and the quantitative measures were described as summary measures (mean, standard deviation). 37065333 15 97 theme two-month 2572:2580 arg1 follow-up 2582:2590 the two-month follow-up 2568:2590 the two-month follow-up 2568:2590 The statistical analysis of the outcomes from the baseline to the two-month follow-up was analyzed using paired t-test. 37065333 16 98 from months 2691:2696 arg1 score 2665:2669 VAS pain score 2656:2669 VAS pain score at baseline and two months 2656:2696 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 16 98 from months 2691:2696 arg1 mean 2648:2651 the mean 2644:2651 the mean of VAS pain score at baseline and two months 2644:2696 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 15 99 theme paired 2611:2616 arg1 t-test 2618:2623 paired t-test 2611:2623 paired t-test 2611:2623 The statistical analysis of the outcomes from the baseline to the two-month follow-up was analyzed using paired t-test. 37065333 15 100 from baseline 2556:2563 arg1 analysis 2522:2529 The statistical analysis 2506:2529 The statistical analysis of the outcomes from the baseline to the two-month follow-up 2506:2590 The statistical analysis of the outcomes from the baseline to the two-month follow-up was analyzed using paired t-test. 37065333 15 100 from baseline 2556:2563 arg1 outcomes 2538:2545 the outcomes 2534:2545 the outcomes from the baseline to the two-month follow-up 2534:2590 The statistical analysis of the outcomes from the baseline to the two-month follow-up was analyzed using paired t-test. 37065333 16 101 dep 3.3 ± 2702:2706 arg1 < 2730:2730 < 2730:2730 < 2730:2730 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 17 102 theme motion 2965:2970 arg1 range 2956:2960 the range 2952:2960 the range of motion 2952:2970 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 6 103 theme serrata 1146:1152 arg1 extract 1154:1160 Boswellia serrata extract 1136:1160 Boswellia serrata extract 1136:1160 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 103 theme serrata 1146:1152 arg1 [Aflapin 1126:1133 Clagen™ [Aflapin 1118:1133 Clagen™ [Aflapin (Boswellia serrata extract) 1118:1161 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 22 104 theme comparison 3596:3605 arg1 NSAIDs 3614:3619 NSAIDs 3614:3619 NSAIDs 3614:3619 To validate these findings further long-term studies with a comparison arm of NSAIDs are needed. 37065333 22 104 theme comparison 3596:3605 arg1 arm 3607:3609 a comparison arm 3594:3609 a comparison arm of NSAIDs 3594:3619 To validate these findings further long-term studies with a comparison arm of NSAIDs are needed. 37065333 20 105 theme positive 3291:3298 arg1 effects 3309:3315 positive adjuvant effects 3291:3315 positive adjuvant effects 3291:3315 Conclusions Clagen™ exerted positive adjuvant effects in the management of OA. 37065333 6 106 theme CurQlife 1271:1278 arg1 efficacy 1106:1113 the efficacy 1102:1113 the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs 1102:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 16 107 from difference 2630:2639 arg1 mean 2648:2651 the mean 2644:2651 the mean of VAS pain score at baseline and two months 2644:2696 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 4 108 theme effective 827:835 arg1 dose 843:846 the lowest effective NSAID dose 816:846 the lowest effective NSAID dose for the shortest time necessary 816:878 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 9 109 theme Knee 1879:1882 arg1 Injury 1884:1889 Knee Injury 1879:1889 Knee Injury 1879:1889 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 11 110 theme 5 2088:2088 arg1 % 2089:2089 % 2089:2089 % 2089:2089 The tests were performed at a 5% significance level (p <0.05). 37065333 6 111 theme long-term 1390:1398 arg1 management 1400:1409 the long-term management 1386:1409 the long-term management of OA instead of NSAIDs 1386:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 22 112 theme further 3563:3569 arg1 studies 3581:3587 further long-term studies 3563:3587 further long-term studies with a comparison arm of NSAIDs 3563:3619 To validate these findings further long-term studies with a comparison arm of NSAIDs are needed. 37065333 6 113 theme Clagen™ 1118:1124 arg1 extract 1154:1160 Boswellia serrata extract 1136:1160 Boswellia serrata extract 1136:1160 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 6 113 theme Clagen™ 1118:1124 arg1 [Aflapin 1126:1133 Clagen™ [Aflapin 1118:1133 Clagen™ [Aflapin (Boswellia serrata extract) 1118:1161 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 12 114 theme summary 2257:2263 arg1 measures 2265:2272 summary measures 2257:2272 summary measures (mean, standard deviation) 2257:2299 The qualitative characteristics were described using absolute and relative frequencies, and the quantitative measures were described as summary measures (mean, standard deviation). 37065333 12 114 theme summary 2257:2263 arg1 measures 2230:2237 the quantitative measures 2213:2237 the quantitative measures 2213:2237 The qualitative characteristics were described using absolute and relative frequencies, and the quantitative measures were described as summary measures (mean, standard deviation). 37065333 12 114 theme summary 2257:2263 arg1 mean 2275:2278 mean 2275:2278 mean 2275:2278 The qualitative characteristics were described using absolute and relative frequencies, and the quantitative measures were described as summary measures (mean, standard deviation). 37065333 17 115 theme goniometer 2843:2852 arg1 value 2854:2858 the goniometer value 2839:2858 the goniometer value of 7.3 ± 7.3 [t 2839:2874 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 15 116 theme outcomes 2538:2545 arg1 analysis 2522:2529 The statistical analysis 2506:2529 The statistical analysis of the outcomes from the baseline to the two-month follow-up 2506:2590 The statistical analysis of the outcomes from the baseline to the two-month follow-up was analyzed using paired t-test. 37065333 6 117 from improvement 1312:1322 arg1 patients 1330:1337 OA patients 1327:1337 OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs 1327:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 10 118 theme Statistical 1967:1977 arg1 analyses 1979:1986 Statistical analyses 1967:1986 Statistical analyses 1967:1986 Statistical analyses were performed according to the results obtained from the parameters. 37065333 5 119 theme OA 1076:1077 arg1 management 1062:1071 the management 1058:1071 the management of OA 1058:1077 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 5 120 theme potential 885:893 arg1 strategy 895:902 One potential strategy 881:902 One potential strategy to achieve this 881:918 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 5 120 theme potential 885:893 arg1 use 927:929 the use 923:929 the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA 923:1077 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 2 121 from pain 492:495 arg1 OA 517:518 OA 517:518 OA 517:518 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 15 122 theme statistical 2510:2520 arg1 analysis 2522:2529 The statistical analysis 2506:2529 The statistical analysis of the outcomes from the baseline to the two-month follow-up 2506:2590 The statistical analysis of the outcomes from the baseline to the two-month follow-up was analyzed using paired t-test. 37065333 3 123 theme multiple 573:580 arg1 effects 590:596 multiple adverse effects 573:596 multiple adverse effects 573:596 However, this comes at a cost of increased risk for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID-induced nephrotoxicity. 37065333 7 124 theme observational 1470:1482 arg1 study 1484:1488 this retrospective observational study 1451:1488 this retrospective observational study 1451:1488 Methodology In this retrospective observational study, a total of 300 patients were screened, of whom 100 OA patients who fulfilled the criteria and agreed to be part of the study were enrolled. 37065333 2 125 from inflammation 501:512 arg1 OA 517:518 OA 517:518 OA 517:518 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 17 126 from improvements 2936:2947 arg1 range 2956:2960 the range 2952:2960 the range of motion 2952:2970 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 9 127 theme improvement 1806:1816 arg1 outcomes 1794:1801 primary outcomes 1786:1801 primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) 1786:1929 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 3 128 theme risk 564:567 arg1 cost 546:549 a cost 544:549 a cost of increased risk for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID-induced nephrotoxicity 544:696 However, this comes at a cost of increased risk for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID-induced nephrotoxicity. 37065333 9 129 dep months 1778:1783 arg1 the 1758:1760 the 1758:1760 the 1758:1760 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 129 dep months 1778:1783 arg1 baseline 1762:1769 baseline 1762:1769 baseline 1762:1769 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 2 130 theme drugs 474:478 arg1 class 465:469 a highly effective class 446:469 a highly effective class of drugs for chronic pain and inflammation in OA 446:518 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 2 130 theme drugs 474:478 arg1 drugs 380:384 Non-steroidal anti-inflammatory drugs 348:384 Non-steroidal anti-inflammatory drugs (NSAIDs) 348:393 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 6 131 theme native 1165:1170 arg1 collagen 1179:1186 native type 2 collagen 1165:1186 native type 2 collagen 1165:1186 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 22 132 dep needed 3625:3630 arg1 validate 3539:3546 validate 3539:3546 To validate these findings 3536:3561 To validate these findings further long-term studies with a comparison arm of NSAIDs are needed. 37065333 0 133 theme Combination 81:91 arg1 Effect 63:68 the Synergistic Effect 47:68 the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis 47:246 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 1 134 theme osteoarthritis 316:329 arg1 management 336:345 osteoarthritis (OA) management 316:345 osteoarthritis (OA) management 316:345 Background Treatment of pain and inflammation form the mainstay of osteoarthritis (OA) management. 37065333 6 135 theme NSAIDs 1428:1433 arg1 management 1400:1409 the long-term management 1386:1409 the long-term management of OA instead of NSAIDs 1386:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 21 136 theme long-term 3508:3516 arg1 effects 3527:3533 their long-term negative effects 3502:3533 their long-term negative effects 3502:3533 The combination not only improved the symptoms and quality of life but, in the light of future perspective, NSAIDs can be withdrawn in OA patients, considering their long-term negative effects. 37065333 8 137 theme knee 1747:1750 arg1 OA 1737:1738 OA 1737:1738 OA of the knee 1737:1750 The data were analyzed to evaluate the efficacy of the nutraceutical formulation Clagen™ in patients with OA of the knee. 37065333 9 138 theme Analog 1832:1837 arg1 VAS 1846:1848 VAS 1846:1848 VAS 1846:1848 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 138 theme Analog 1832:1837 arg1 Scale 1839:1843 the Visual Analog Scale 1821:1843 the Visual Analog Scale 1821:1843 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 8 139 from efficacy 1670:1677 arg1 patients 1723:1730 patients 1723:1730 patients with OA of the knee 1723:1750 The data were analyzed to evaluate the efficacy of the nutraceutical formulation Clagen™ in patients with OA of the knee. 37065333 0 140 theme Alfapin 96:102 arg1 Combination 81:91 a Novel Combination 73:91 a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals 73:192 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 21 141 dep perspective 3437:3447 arg1 the 3417:3419 the 3417:3419 the 3417:3419 The combination not only improved the symptoms and quality of life but, in the light of future perspective, NSAIDs can be withdrawn in OA patients, considering their long-term negative effects. 37065333 21 141 dep perspective 3437:3447 arg1 light 3421:3425 light 3421:3425 light 3421:3425 The combination not only improved the symptoms and quality of life but, in the light of future perspective, NSAIDs can be withdrawn in OA patients, considering their long-term negative effects. 37065333 18 142 theme composite 3034:3042 arg1 score 3049:3053 the composite KOOS score 3030:3053 the composite KOOS score by 10.8% at the end of two months 3030:3087 It was also observed that Clagen™ significantly improved the composite KOOS score by 10.8% at the end of two months. 37065333 0 143 from Effect 63:68 arg1 Improvement 213:223 the Symptomatic Improvement 197:223 the Symptomatic Improvement of Knee Osteoarthritis 197:246 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 8 144 with patients 1723:1730 arg1 OA 1737:1738 OA 1737:1738 OA of the knee 1737:1750 The data were analyzed to evaluate the efficacy of the nutraceutical formulation Clagen™ in patients with OA of the knee. 37065333 0 145 theme Native 106:111 arg1 Collagen 120:127 Native Type 2 Collagen 106:127 Native Type 2 Collagen 106:127 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 1 146 theme management 336:345 arg1 mainstay 304:311 the mainstay 300:311 the mainstay of osteoarthritis (OA) management 300:345 Background Treatment of pain and inflammation form the mainstay of osteoarthritis (OA) management. 37065333 5 147 theme osteoarthritis 952:965 arg1 DMOADs 974:979 DMOADs 974:979 DMOADs 974:979 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 5 147 theme osteoarthritis 952:965 arg1 drugs 967:971 disease-modifying osteoarthritis drugs 934:971 disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs 934:1052 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 18 148 theme months 3082:3087 arg1 end 3071:3073 the end 3067:3073 the end of two months 3067:3087 It was also observed that Clagen™ significantly improved the composite KOOS score by 10.8% at the end of two months. 37065333 14 149 theme body 2468:2471 arg1 kg/m2 2499:2503 24.5 ± 3.5 kg/m2 2488:2503 24.5 ± 3.5 kg/m2 2488:2503 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 14 149 theme body 2468:2471 arg1 index 2478:2482 the mean body mass index 2459:2482 the mean body mass index 2459:2482 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 2 150 theme chronic 484:490 arg1 pain 492:495 chronic pain 484:495 chronic pain 484:495 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 5 151 dep strategy 895:902 arg1 achieve 907:913 achieve 907:913 to achieve this 904:918 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 16 152 theme = 2720:2720 arg1 97 2716:2717 97 2716:2717 97 2716:2717 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 16 152 theme = 2720:2720 arg1 [t 2712:2713 1.8 [t 2708:2713 1.8 [t (97) = 18.2 2708:2725 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 0 153 theme Retrospective 2:14 arg1 Study 30:34 A Retrospective Observational Study 0:34 A Retrospective Observational Study 0:34 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 0 154 theme Knee 228:231 arg1 Osteoarthritis 233:246 Knee Osteoarthritis 228:246 Knee Osteoarthritis 228:246 A Retrospective Observational Study Evaluating the Synergistic Effect of a Novel Combination of Alfapin + Native Type 2 Collagen + Mobilee (Hyaluronic Acid) + CurQlife (Curcumin) Nutraceuticals in the Symptomatic Improvement of Knee Osteoarthritis. 37065333 16 155 dep < 2730:2730 arg1 p 2728:2728 p 2728:2728 p 2728:2728 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 16 155 dep < 2730:2730 arg1 97 2716:2717 97 2716:2717 97 2716:2717 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 16 155 dep < 2730:2730 arg1 [t 2712:2713 1.8 [t 2708:2713 1.8 [t (97) = 18.2 2708:2725 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 37065333 2 156 theme anti-inflammatory 362:378 arg1 class 465:469 a highly effective class 446:469 a highly effective class of drugs for chronic pain and inflammation in OA 446:518 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 2 156 theme anti-inflammatory 362:378 arg1 NSAIDs 387:392 NSAIDs 387:392 NSAIDs 387:392 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 2 156 theme anti-inflammatory 362:378 arg1 drugs 380:384 Non-steroidal anti-inflammatory drugs 348:384 Non-steroidal anti-inflammatory drugs (NSAIDs) 348:393 Non-steroidal anti-inflammatory drugs (NSAIDs), due to their inflammation-blocking mechanism, are a highly effective class of drugs for chronic pain and inflammation in OA. 37065333 6 157 from management 1400:1409 arg1 effective 1373:1381 effective 1373:1381 effective 1373:1381 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 9 158 from outcomes 1794:1801 arg1 VAS 1846:1848 VAS 1846:1848 VAS 1846:1848 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 158 from outcomes 1794:1801 arg1 Score 1918:1922 Osteoarthritis Outcome Score 1895:1922 Osteoarthritis Outcome Score (KOOS) 1895:1929 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 158 from outcomes 1794:1801 arg1 score 1851:1855 score 1851:1855 score 1851:1855 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 158 from outcomes 1794:1801 arg1 KOOS 1925:1928 KOOS 1925:1928 KOOS 1925:1928 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 158 from outcomes 1794:1801 arg1 range 1858:1862 range 1858:1862 range of motion 1858:1872 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 158 from outcomes 1794:1801 arg1 Injury 1884:1889 Knee Injury 1879:1889 Knee Injury 1879:1889 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 158 from outcomes 1794:1801 arg1 Scale 1839:1843 the Visual Analog Scale 1821:1843 the Visual Analog Scale 1821:1843 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 21 159 theme life 3404:3407 arg1 symptoms 3380:3387 the symptoms 3376:3387 the symptoms 3376:3387 The combination not only improved the symptoms and quality of life but, in the light of future perspective, NSAIDs can be withdrawn in OA patients, considering their long-term negative effects. 37065333 21 159 theme life 3404:3407 arg1 quality 3393:3399 quality 3393:3399 quality of life 3393:3407 The combination not only improved the symptoms and quality of life but, in the light of future perspective, NSAIDs can be withdrawn in OA patients, considering their long-term negative effects. 37065333 19 160 theme KOOS 3101:3104 arg1 scores 3106:3111 KOOS scores 3101:3111 KOOS scores for Symptoms, Function, and Quality of Life 3101:3155 Similarly, KOOS scores for Symptoms, Function, and Quality of Life showed improvements of 9.6%, 9.8%, and 7.8%, respectively, and were statistically significant (p < 0.05). 37065333 19 161 theme Life 3152:3155 arg1 Function 3127:3134 Function 3127:3134 Function 3127:3134 Similarly, KOOS scores for Symptoms, Function, and Quality of Life showed improvements of 9.6%, 9.8%, and 7.8%, respectively, and were statistically significant (p < 0.05). 37065333 19 161 theme Life 3152:3155 arg1 Quality 3141:3147 Quality 3141:3147 Quality of Life 3141:3155 Similarly, KOOS scores for Symptoms, Function, and Quality of Life showed improvements of 9.6%, 9.8%, and 7.8%, respectively, and were statistically significant (p < 0.05). 37065333 19 161 theme Life 3152:3155 arg1 Symptoms 3117:3124 Symptoms 3117:3124 Symptoms 3117:3124 Similarly, KOOS scores for Symptoms, Function, and Quality of Life showed improvements of 9.6%, 9.8%, and 7.8%, respectively, and were statistically significant (p < 0.05). 37065333 6 162 theme symptomatic 1300:1310 arg1 improvement 1312:1322 the symptomatic improvement 1296:1322 the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs 1296:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 5 163 theme anti-inflammatory 993:1009 arg1 properties 1025:1034 anti-inflammatory and analgesic properties 993:1034 anti-inflammatory and analgesic properties instead of NSAIDs 993:1052 One potential strategy to achieve this is the use of disease-modifying osteoarthritis drugs (DMOADs) containing anti-inflammatory and analgesic properties instead of NSAIDs for the management of OA. 37065333 4 164 theme medical 782:788 arg1 societies 790:798 medical societies 782:798 medical societies 782:798 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 6 165 from effective 1373:1381 arg1 management 1400:1409 the long-term management 1386:1409 the long-term management of OA instead of NSAIDs 1386:1433 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 17 166 from difference 2813:2822 arg1 -10.0 2883:2887 -10.0 2883:2887 -10.0 2883:2887 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 17 166 from difference 2813:2822 arg1 mean 2831:2834 the mean 2827:2834 the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] 2827:2898 Moreover, the difference in the mean of the goniometer value of 7.3 ± 7.3 [t (98) = -10.0, p < 0.05] indicated statistically significant improvements in the range of motion. 37065333 20 167 theme OA 3338:3339 arg1 the management 3320:3333 the management 3320:3333 the management of OA 3320:3339 Conclusions Clagen™ exerted positive adjuvant effects in the management of OA. 37065333 3 168 theme cardiovascular 636:649 arg1 effects 656:662 cardiovascular side effects 636:662 cardiovascular side effects 636:662 However, this comes at a cost of increased risk for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID-induced nephrotoxicity. 37065333 6 169 dep as 1347:1348 arg1 effective 1373:1381 effective 1373:1381 effective 1373:1381 This study focuses on the efficacy of Clagen™ [Aflapin (Boswellia serrata extract) + native type 2 collagen + Mobilee (hyaluronic acid (60-70%), polysaccharides (>10%), and collagen (>5%)) + CurQlife (Curcumin)] for the symptomatic improvement in OA patients as well as if this combination is effective in the long-term management of OA instead of NSAIDs. 37065333 14 170 theme patients 2423:2430 arg1 age 2412:2414 The mean age 2403:2414 The mean age of the patients 2403:2430 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 14 170 theme patients 2423:2430 arg1 years 2448:2452 50.6 ± 13.9 years 2436:2452 50.6 ± 13.9 years 2436:2452 The mean age of the patients was 50.6 ± 13.9 years, and the mean body mass index was 24.5 ± 3.5 kg/m2. 37065333 11 171 theme p 2111:2111 arg1 level 2104:2108 a 5% significance level 2086:2108 a 5% significance level (p <0.05) 2086:2118 The tests were performed at a 5% significance level (p <0.05). 37065333 11 171 theme p 2111:2111 arg1 <0.05 2113:2117 p <0.05 2111:2117 p <0.05 2111:2117 The tests were performed at a 5% significance level (p <0.05). 37065333 12 172 theme absolute 2174:2181 arg1 frequencies 2196:2206 absolute and relative frequencies 2174:2206 absolute and relative frequencies 2174:2206 The qualitative characteristics were described using absolute and relative frequencies, and the quantitative measures were described as summary measures (mean, standard deviation). 37065333 4 173 theme event 744:748 arg1 risk 725:728 the potential risk 711:728 the potential risk of an adverse event 711:748 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 4 174 theme numerous 751:758 arg1 bodies 771:776 numerous regulatory bodies 751:776 numerous regulatory bodies 751:776 To minimize the potential risk of an adverse event, numerous regulatory bodies and medical societies recommend using the lowest effective NSAID dose for the shortest time necessary. 37065333 19 175 theme % 3189:3189 arg1 improvements 3164:3175 improvements 3164:3175 improvements of 9.6%, 9.8%, and 7.8%, respectively 3164:3213 Similarly, KOOS scores for Symptoms, Function, and Quality of Life showed improvements of 9.6%, 9.8%, and 7.8%, respectively, and were statistically significant (p < 0.05). 37065333 12 176 theme relative 2187:2194 arg1 frequencies 2196:2206 absolute and relative frequencies 2174:2206 absolute and relative frequencies 2174:2206 The qualitative characteristics were described using absolute and relative frequencies, and the quantitative measures were described as summary measures (mean, standard deviation). 37065333 9 177 theme Outcome 1910:1916 arg1 KOOS 1925:1928 KOOS 1925:1928 KOOS 1925:1928 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 9 177 theme Outcome 1910:1916 arg1 Score 1918:1922 Osteoarthritis Outcome Score 1895:1922 Osteoarthritis Outcome Score (KOOS) 1895:1929 From the baseline to two months, primary outcomes of improvement in the Visual Analog Scale (VAS) score, range of motion, and Knee Injury and Osteoarthritis Outcome Score (KOOS) were measured at monthly follow-up. 37065333 16 178 theme pain 2660:2663 arg1 score 2665:2669 VAS pain score 2656:2669 VAS pain score at baseline and two months 2656:2696 The difference in the mean of VAS pain score at baseline and two months was 3.3 ± 1.8 [t (97) = 18.2; p < 0.05], which showed a significant reduction in pain at two months. 36131725 2 0 theme plants 363:368 arg1 capability 349:358 The capability 345:358 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation 345:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 4 1 theme vaccine 971:977 arg1 candidates 979:988 vaccine candidates 971:988 vaccine candidates 971:988 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 4 1 theme vaccine 971:977 arg1 proteins 1003:1010 therapeutic proteins 991:1010 therapeutic proteins 991:1010 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 4 2 theme proteins 928:935 arg1 engineering 901:911 engineering 901:911 engineering 901:911 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 4 2 theme proteins 928:935 arg1 development 885:895 development 885:895 development 885:895 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 7 3 theme comprehensive 1536:1548 arg1 manual 1562:1567 a comprehensive instruction manual 1534:1567 a comprehensive instruction manual describing the procedure 1534:1592 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 8 4 theme various 1985:1991 arg1 components 1997:2006 the various kit components 1981:2006 the various kit components 1981:2006 In this article, we describe the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components. 36131725 1 5 theme Recombinant 174:184 arg1 expression 186:195 Recombinant expression 174:195 Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants 174:265 Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants has developed into a robust and versatile method to rapidly produce proteins. 36131725 4 6 theme various 941:947 arg1 purposes 949:956 various purposes 941:956 various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications 941:1083 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 8 7 theme kit 1843:1845 arg1 concept 1825:1831 the initial concept 1813:1831 the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components 1813:2006 In this article, we describe the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components. 36131725 9 8 theme property 2049:2056 arg1 rights 2058:2063 intellectual property rights 2036:2063 intellectual property rights 2036:2063 We cover aspects including intellectual property rights, freedom-to-operate (FTO), safety regulations for distributing genetically-modified organisms (GMOs), as well as export and import regulations. 36131725 6 9 theme EU-funded 1440:1448 arg1 Pharma-Factory 1471:1484 the EU-funded Horizon 2020 project Pharma-Factory 1436:1484 the EU-funded Horizon 2020 project Pharma-Factory 1436:1484 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 5 10 theme plant 1179:1183 arg1 research 1185:1192 plant research 1179:1192 plant research 1179:1192 Despite these advantages the technology is currently not being used outside the community of plant research. 36131725 8 11 theme educational 1851:1861 arg1 purposes 1905:1912 educational as well as research and development (R&D) purposes 1851:1912 educational as well as research and development (R&D) purposes 1851:1912 In this article, we describe the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components. 36131725 1 12 theme transient 226:234 arg1 ATT 252:254 ATT 252:254 ATT 252:254 Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants has developed into a robust and versatile method to rapidly produce proteins. 36131725 1 12 theme transient 226:234 arg1 transformation 236:249 Agrobacterium-mediated transient transformation 203:249 Agrobacterium-mediated transient transformation (ATT) of plants 203:265 Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants has developed into a robust and versatile method to rapidly produce proteins. 36131725 2 13 theme established 588:598 arg1 hosts 645:649 the established microbial, especially prokaryotic expression hosts 584:649 the established microbial, especially prokaryotic expression hosts 584:649 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 4 14 dep different 1033:1041 arg1 technical 1062:1070 technical 1062:1070 technical 1062:1070 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 4 14 dep different 1033:1041 arg1 pharmaceutical 1043:1056 pharmaceutical 1043:1056 pharmaceutical 1043:1056 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 4 15 dep development 885:895 arg1 the 881:883 the 881:883 the 881:883 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 6 16 theme protein 1338:1344 arg1 production 1346:1355 recombinant protein production 1326:1355 recombinant protein production using ATT 1326:1365 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 2 17 link N-linked 530:537 arg1 glycosylation 539:551 N-linked glycosylation 530:551 N-linked glycosylation 530:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 0 18 theme regulatory 139:148 arg1 implications 160:171 regulatory and legal implications 139:171 regulatory and legal implications 139:171 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 36131725 8 19 theme research 1874:1881 arg1 purposes 1905:1912 educational as well as research and development (R&D) purposes 1851:1912 educational as well as research and development (R&D) purposes 1851:1912 In this article, we describe the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components. 36131725 4 20 dep make 817:820 arg1 Taken 787:791 Taken 787:791 Taken together 787:800 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 10 21 theme kit 2267:2269 arg1 components 2245:2254 important components 2235:2254 important components of the ATT kit 2235:2269 Our analysis reveals that important components of the ATT kit are freely available for research purposes but not or only with considerable effort for commercial use and distribution. 36131725 0 22 theme legal 154:158 arg1 implications 160:171 regulatory and legal implications 139:171 regulatory and legal implications 139:171 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 36131725 7 23 theme organisms 1729:1737 arg1 provision 1665:1673 provision 1665:1673 provision 1665:1673 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 7 23 theme organisms 1729:1737 arg1 use 1694:1696 use 1694:1696 use 1694:1696 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 7 23 theme organisms 1729:1737 arg1 dissemination 1676:1688 dissemination 1676:1688 dissemination 1676:1688 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 9 24 theme safety 2092:2097 arg1 regulations 2099:2109 safety regulations 2092:2109 safety regulations for distributing genetically-modified organisms (GMOs) 2092:2164 We cover aspects including intellectual property rights, freedom-to-operate (FTO), safety regulations for distributing genetically-modified organisms (GMOs), as well as export and import regulations. 36131725 0 25 theme protein 55:61 arg1 production 63:72 recombinant protein production 43:72 recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications 43:171 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 36131725 3 26 theme mammalian 678:686 arg1 cultures 693:700 mammalian cell cultures 678:700 mammalian cell cultures 678:700 Compared to production in mammalian cell cultures, ATT requires lower skills, simple technical equipment and cheaper media components. 36131725 7 27 theme materials 1715:1723 arg1 provision 1665:1673 provision 1665:1673 provision 1665:1673 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 7 27 theme materials 1715:1723 arg1 use 1694:1696 use 1694:1696 use 1694:1696 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 7 27 theme materials 1715:1723 arg1 dissemination 1676:1688 dissemination 1676:1688 dissemination 1676:1688 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 9 28 theme genetically-modified 2128:2147 arg1 organisms 2149:2157 distributing genetically-modified organisms 2115:2157 distributing genetically-modified organisms (GMOs) 2115:2164 We cover aspects including intellectual property rights, freedom-to-operate (FTO), safety regulations for distributing genetically-modified organisms (GMOs), as well as export and import regulations. 36131725 9 28 theme genetically-modified 2128:2147 arg1 GMOs 2160:2163 GMOs 2160:2163 GMOs 2160:2163 We cover aspects including intellectual property rights, freedom-to-operate (FTO), safety regulations for distributing genetically-modified organisms (GMOs), as well as export and import regulations. 36131725 6 29 theme Pharma-Factory 1471:1484 arg1 objectives 1422:1431 the objectives 1418:1431 the objectives of the EU-funded Horizon 2020 project Pharma-Factory 1418:1484 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 2 30 theme hetero-multimeric 411:427 arg1 proteins 444:451 even homo- and hetero-multimeric complex folded proteins 396:451 even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds 396:477 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 2 30 theme hetero-multimeric 411:427 arg1 glycosylation 539:551 N-linked glycosylation 530:551 N-linked glycosylation 530:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 0 31 theme use-A 105:109 arg1 journey 111:117 educational and commercial use-A journey 78:117 educational and commercial use-A journey 78:117 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 36131725 8 32 theme regulatory 1931:1940 arg1 implications 1952:1963 the specific regulatory and legal implications 1918:1963 the specific regulatory and legal implications associated with the various kit components 1918:2006 In this article, we describe the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components. 36131725 2 33 theme other 483:487 arg1 modifications 508:520 other post-translational modifications 483:520 other post-translational modifications such as N-linked glycosylation 483:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 2 33 theme other 483:487 arg1 glycosylation 539:551 N-linked glycosylation 530:551 N-linked glycosylation 530:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 2 34 theme homo- 401:405 arg1 proteins 444:451 even homo- and hetero-multimeric complex folded proteins 396:451 even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds 396:477 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 2 34 theme homo- 401:405 arg1 glycosylation 539:551 N-linked glycosylation 530:551 N-linked glycosylation 530:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 1 35 theme robust 288:293 arg1 method 309:314 a robust and versatile method 286:314 a robust and versatile method to rapidly produce proteins 286:342 Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants has developed into a robust and versatile method to rapidly produce proteins. 36131725 8 36 theme legal 1946:1950 arg1 implications 1952:1963 the specific regulatory and legal implications 1918:1963 the specific regulatory and legal implications associated with the various kit components 1918:2006 In this article, we describe the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components. 36131725 6 37 theme educational 1373:1383 arg1 context 1399:1405 an educational or commercial context 1370:1405 an educational or commercial context 1370:1405 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 10 38 theme considerable 2335:2346 arg1 effort 2348:2353 considerable effort 2335:2353 considerable effort for commercial use and distribution 2335:2389 Our analysis reveals that important components of the ATT kit are freely available for research purposes but not or only with considerable effort for commercial use and distribution. 36131725 1 39 theme versatile 299:307 arg1 method 309:314 a robust and versatile method 286:314 a robust and versatile method to rapidly produce proteins 286:342 Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants has developed into a robust and versatile method to rapidly produce proteins. 36131725 3 40 theme lower 716:720 arg1 skills 722:727 lower skills 716:727 lower skills 716:727 Compared to production in mammalian cell cultures, ATT requires lower skills, simple technical equipment and cheaper media components. 36131725 3 41 from production 664:673 arg1 cultures 693:700 mammalian cell cultures 678:700 mammalian cell cultures 678:700 Compared to production in mammalian cell cultures, ATT requires lower skills, simple technical equipment and cheaper media components. 36131725 2 42 theme folded 437:442 arg1 proteins 444:451 even homo- and hetero-multimeric complex folded proteins 396:451 even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds 396:477 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 2 42 theme folded 437:442 arg1 glycosylation 539:551 N-linked glycosylation 530:551 N-linked glycosylation 530:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 0 43 theme agroinfiltration 18:33 arg1 kit 35:37 an agroinfiltration kit 15:37 an agroinfiltration kit 15:37 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 36131725 11 44 theme considerations 2421:2434 arg1 number 2411:2416 a number 2409:2416 a number of considerations and requirements that need to be met in order to successfully disseminate such a kit in the future 2409:2533 We conclude with a number of considerations and requirements that need to be met in order to successfully disseminate such a kit in the future. 36131725 3 45 theme technical 737:745 arg1 equipment 747:755 simple technical equipment 730:755 simple technical equipment 730:755 Compared to production in mammalian cell cultures, ATT requires lower skills, simple technical equipment and cheaper media components. 36131725 6 46 dep kit 1227:1229 arg1 containing 1231:1240 containing 1231:1240 containing all the information 1231:1260 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 7 47 theme legal 1631:1635 arg1 aspects 1637:1643 regulatory and legal aspects 1616:1643 regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT 1616:1761 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 2 48 theme complex 429:435 arg1 proteins 444:451 even homo- and hetero-multimeric complex folded proteins 396:451 even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds 396:477 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 2 48 theme complex 429:435 arg1 glycosylation 539:551 N-linked glycosylation 530:551 N-linked glycosylation 530:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 5 49 used used 1149:1152 arg2 technology 1115:1124 the technology 1111:1124 the technology 1111:1124 Despite these advantages the technology is currently not being used outside the community of plant research. 36131725 7 50 theme regulatory 1616:1625 arg1 aspects 1637:1643 regulatory and legal aspects 1616:1643 regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT 1616:1761 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 3 51 theme media 769:773 arg1 components 775:784 cheaper media components 761:784 cheaper media components 761:784 Compared to production in mammalian cell cultures, ATT requires lower skills, simple technical equipment and cheaper media components. 36131725 11 52 theme requirements 2440:2451 arg1 number 2411:2416 a number 2409:2416 a number of considerations and requirements that need to be met in order to successfully disseminate such a kit in the future 2409:2533 We conclude with a number of considerations and requirements that need to be met in order to successfully disseminate such a kit in the future. 36131725 6 53 theme commercial 1388:1397 arg1 context 1399:1405 an educational or commercial context 1370:1405 an educational or commercial context 1370:1405 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 10 54 theme important 2235:2243 arg1 components 2245:2254 important components 2235:2254 important components of the ATT kit 2235:2269 Our analysis reveals that important components of the ATT kit are freely available for research purposes but not or only with considerable effort for commercial use and distribution. 36131725 8 55 theme kit 1993:1995 arg1 components 1997:2006 the various kit components 1981:2006 the various kit components 1981:2006 In this article, we describe the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components. 36131725 8 56 theme initial 1817:1823 arg1 concept 1825:1831 the initial concept 1813:1831 the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components 1813:2006 In this article, we describe the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components. 36131725 2 57 dep microbial 600:608 arg1 prokaryotic 622:632 prokaryotic 622:632 prokaryotic 622:632 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 4 58 theme recombinant 916:926 arg1 proteins 928:935 recombinant proteins 916:935 recombinant proteins 916:935 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 7 59 theme instruction 1550:1560 arg1 manual 1562:1567 a comprehensive instruction manual 1534:1567 a comprehensive instruction manual describing the procedure 1534:1592 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 7 60 theme complex 1768:1774 arg1 clarification 1599:1611 the clarification 1595:1611 the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT 1595:1761 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 7 60 theme complex 1768:1774 arg1 matter 1776:1781 a complex matter 1766:1781 a complex matter 1766:1781 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 9 61 theme import 2189:2194 arg1 regulations 2196:2206 export and import regulations 2178:2206 export and import regulations 2178:2206 We cover aspects including intellectual property rights, freedom-to-operate (FTO), safety regulations for distributing genetically-modified organisms (GMOs), as well as export and import regulations. 36131725 9 62 theme intellectual 2036:2047 arg1 rights 2058:2063 intellectual property rights 2036:2063 intellectual property rights 2036:2063 We cover aspects including intellectual property rights, freedom-to-operate (FTO), safety regulations for distributing genetically-modified organisms (GMOs), as well as export and import regulations. 36131725 6 63 theme Horizon 1450:1456 arg1 Pharma-Factory 1471:1484 the EU-funded Horizon 2020 project Pharma-Factory 1436:1484 the EU-funded Horizon 2020 project Pharma-Factory 1436:1484 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 8 64 theme ATT 1839:1841 arg1 kit 1843:1845 an ATT kit 1836:1845 an ATT kit 1836:1845 In this article, we describe the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components. 36131725 1 65 theme Agrobacterium-mediated 203:224 arg1 ATT 252:254 ATT 252:254 ATT 252:254 Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants has developed into a robust and versatile method to rapidly produce proteins. 36131725 1 65 theme Agrobacterium-mediated 203:224 arg1 transformation 236:249 Agrobacterium-mediated transient transformation 203:249 Agrobacterium-mediated transient transformation (ATT) of plants 203:265 Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants has developed into a robust and versatile method to rapidly produce proteins. 36131725 2 66 theme microbial 600:608 arg1 hosts 645:649 the established microbial, especially prokaryotic expression hosts 584:649 the established microbial, especially prokaryotic expression hosts 584:649 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 10 67 theme ATT 2263:2265 arg1 kit 2267:2269 the ATT kit 2259:2269 the ATT kit 2259:2269 Our analysis reveals that important components of the ATT kit are freely available for research purposes but not or only with considerable effort for commercial use and distribution. 36131725 7 68 dep materials 1715:1723 arg1 the 1701:1703 the 1701:1703 the 1701:1703 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 6 69 theme objectives 1422:1431 arg1 one 1411:1413 one 1411:1413 one 1411:1413 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 6 69 theme objectives 1422:1431 arg1 objectives 1422:1431 the objectives 1418:1431 the objectives of the EU-funded Horizon 2020 project Pharma-Factory 1418:1484 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 2 70 theme expression 634:643 arg1 hosts 645:649 the established microbial, especially prokaryotic expression hosts 584:649 the established microbial, especially prokaryotic expression hosts 584:649 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 6 71 theme recombinant 1326:1336 arg1 production 1346:1355 recombinant protein production 1326:1355 recombinant protein production using ATT 1326:1365 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 0 72 theme implications 160:171 arg1 forest 129:134 a forest 127:134 a forest of regulatory and legal implications 127:171 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 36131725 3 73 theme cell 688:691 arg1 cultures 693:700 mammalian cell cultures 678:700 mammalian cell cultures 678:700 Compared to production in mammalian cell cultures, ATT requires lower skills, simple technical equipment and cheaper media components. 36131725 4 74 theme therapeutic 991:1001 arg1 candidates 979:988 vaccine candidates 971:988 vaccine candidates 971:988 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 4 74 theme therapeutic 991:1001 arg1 proteins 1003:1010 therapeutic proteins 991:1010 therapeutic proteins 991:1010 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 7 75 theme different 1705:1713 arg1 materials 1715:1723 materials 1715:1723 materials 1715:1723 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 10 76 theme research 2296:2303 arg1 purposes 2305:2312 research purposes 2296:2312 research purposes 2296:2312 Our analysis reveals that important components of the ATT kit are freely available for research purposes but not or only with considerable effort for commercial use and distribution. 36131725 0 77 theme educational 78:88 arg1 journey 111:117 educational and commercial use-A journey 78:117 educational and commercial use-A journey 78:117 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 36131725 2 78 theme N-linked 530:537 arg1 glycosylation 539:551 N-linked glycosylation 530:551 N-linked glycosylation 530:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 9 79 theme distributing 2115:2126 arg1 organisms 2149:2157 distributing genetically-modified organisms 2115:2157 distributing genetically-modified organisms (GMOs) 2115:2164 We cover aspects including intellectual property rights, freedom-to-operate (FTO), safety regulations for distributing genetically-modified organisms (GMOs), as well as export and import regulations. 36131725 9 79 theme distributing 2115:2126 arg1 GMOs 2160:2163 GMOs 2160:2163 GMOs 2160:2163 We cover aspects including intellectual property rights, freedom-to-operate (FTO), safety regulations for distributing genetically-modified organisms (GMOs), as well as export and import regulations. 36131725 0 80 theme commercial 94:103 arg1 journey 111:117 educational and commercial use-A journey 78:117 educational and commercial use-A journey 78:117 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 36131725 4 81 theme different 1033:1041 arg1 applications 1072:1083 different pharmaceutical and technical applications 1033:1083 different pharmaceutical and technical applications 1033:1083 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 6 82 theme project 1463:1469 arg1 Pharma-Factory 1471:1484 the EU-funded Horizon 2020 project Pharma-Factory 1436:1484 the EU-funded Horizon 2020 project Pharma-Factory 1436:1484 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 10 83 theme commercial 2359:2368 arg1 use 2370:2372 commercial use 2359:2372 commercial use 2359:2372 Our analysis reveals that important components of the ATT kit are freely available for research purposes but not or only with considerable effort for commercial use and distribution. 36131725 8 84 theme specific 1922:1929 arg1 implications 1952:1963 the specific regulatory and legal implications 1918:1963 the specific regulatory and legal implications associated with the various kit components 1918:2006 In this article, we describe the initial concept of an ATT kit for educational as well as research and development (R&D) purposes and the specific regulatory and legal implications associated with the various kit components. 36131725 5 85 theme research 1185:1192 arg1 community 1166:1174 the community 1162:1174 the community of plant research 1162:1192 Despite these advantages the technology is currently not being used outside the community of plant research. 36131725 10 86 with available 2282:2290 arg1 effort 2348:2353 considerable effort 2335:2353 considerable effort for commercial use and distribution 2335:2389 Our analysis reveals that important components of the ATT kit are freely available for research purposes but not or only with considerable effort for commercial use and distribution. 36131725 2 87 theme disulfide 463:471 arg1 bonds 473:477 disulfide bonds 463:477 disulfide bonds 463:477 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 2 88 dep capability 349:358 arg1 synthesize 385:394 synthesize 385:394 to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation 370:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 0 89 theme kit 35:37 arg1 concept 4:10 The concept 0:10 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 0:172 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 36131725 9 90 theme export 2178:2183 arg1 regulations 2196:2206 export and import regulations 2178:2206 export and import regulations 2178:2206 We cover aspects including intellectual property rights, freedom-to-operate (FTO), safety regulations for distributing genetically-modified organisms (GMOs), as well as export and import regulations. 36131725 6 91 dep design 1199:1204 arg1 The 1195:1197 The 1195:1197 The 1195:1197 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 6 92 theme 2020 1458:1461 arg1 Pharma-Factory 1471:1484 the EU-funded Horizon 2020 project Pharma-Factory 1436:1484 the EU-funded Horizon 2020 project Pharma-Factory 1436:1484 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 0 93 theme recombinant 43:53 arg1 production 63:72 recombinant protein production 43:72 recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications 43:171 The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications. 36131725 2 94 theme post-translational 489:506 arg1 modifications 508:520 other post-translational modifications 483:520 other post-translational modifications such as N-linked glycosylation 483:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 2 94 theme post-translational 489:506 arg1 glycosylation 539:551 N-linked glycosylation 530:551 N-linked glycosylation 530:551 The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. 36131725 3 95 theme simple 730:735 arg1 equipment 747:755 simple technical equipment 730:755 simple technical equipment 730:755 Compared to production in mammalian cell cultures, ATT requires lower skills, simple technical equipment and cheaper media components. 36131725 6 96 theme kit 1227:1229 arg1 realization 1210:1220 realization 1210:1220 realization 1210:1220 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 6 96 theme kit 1227:1229 arg1 design 1199:1204 design 1199:1204 design 1199:1204 The design and realization of a kit containing all the information, instructions and ideally also the material required to perform recombinant protein production using ATT in an educational or commercial context was one of the objectives of the EU-funded Horizon 2020 project Pharma-Factory. 36131725 4 97 theme R&D 854:856 arg1 applications 858:869 R&D applications 854:869 R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications 854:1083 Taken together these features make the method optimally suited for R&D applications involving the development and engineering of recombinant proteins for various purposes ranging from vaccine candidates, therapeutic proteins, towards enzymes for different pharmaceutical and technical applications. 36131725 7 98 dep provision 1665:1673 arg1 the 1661:1663 the 1661:1663 the 1661:1663 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 7 99 theme aspects 1637:1643 arg1 clarification 1599:1611 the clarification 1595:1611 the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT 1595:1761 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 7 99 theme aspects 1637:1643 arg1 matter 1776:1781 a complex matter 1766:1781 a complex matter 1766:1781 While it is pretty straightforward to assemble a comprehensive instruction manual describing the procedure, the clarification of regulatory and legal aspects associated with the provision, dissemination and use of the different materials and organisms required to perform ATT is a complex matter. 36131725 3 100 theme cheaper 761:767 arg1 components 775:784 cheaper media components 761:784 cheaper media components 761:784 Compared to production in mammalian cell cultures, ATT requires lower skills, simple technical equipment and cheaper media components. 36131725 1 101 theme plants 260:265 arg1 ATT 252:254 ATT 252:254 ATT 252:254 Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants has developed into a robust and versatile method to rapidly produce proteins. 36131725 1 101 theme plants 260:265 arg1 transformation 236:249 Agrobacterium-mediated transient transformation 203:249 Agrobacterium-mediated transient transformation (ATT) of plants 203:265 Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants has developed into a robust and versatile method to rapidly produce proteins. 35957920 13 0 dep Conclusion 1484:1493 arg1 provides 1506:1513 provides 1506:1513 provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD 1506:1620 Conclusion This study provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD. 35957920 6 1 theme gene 926:929 arg1 levels 942:947 lower ST8SIA2 gene expression levels 912:947 lower ST8SIA2 gene expression levels 912:947 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 7 2 theme = 1098:1098 arg1 r 1096:1096 r 1096:1096 r = 0.381 1096:1104 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 3 3 from information 495:505 arg1 correlation 514:524 the correlation 510:524 the correlation between ST8SIA2 and autistic behavioral symptoms 510:573 However, there is limited information on the correlation between ST8SIA2 and autistic behavioral symptoms. 35957920 1 4 theme sialic 266:271 arg1 SA 279:280 SA 279:280 SA 279:280 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 1 4 theme sialic 266:271 arg1 acid 273:276 sialic acid 266:276 sialic acid (SA) 266:281 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 6 5 theme lower 912:916 arg1 levels 942:947 lower ST8SIA2 gene expression levels 912:947 lower ST8SIA2 gene expression levels 912:947 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 0 6 with children 66:73 arg1 disorder 96:103 autism spectrum disorder 80:103 autism spectrum disorder 80:103 The association between ST8SIA2 gene and behavioral phenotypes in children with autism spectrum disorder. 35957920 3 7 theme autistic 546:553 arg1 symptoms 566:573 autistic behavioral symptoms 546:573 autistic behavioral symptoms 546:573 However, there is limited information on the correlation between ST8SIA2 and autistic behavioral symptoms. 35957920 1 8 from CMP-SA 288:293 arg1 transfer 254:261 the transfer 250:261 the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins 250:340 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 1 9 theme type 197:200 arg1 alpha-2,8-sialyltransferase 147:173 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 106:175 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) 106:185 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 1 9 theme type 197:200 arg1 protein 214:220 a type II membrane protein 195:220 a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins 195:340 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 10 10 theme ST8SIA2 1296:1302 arg1 gene 1304:1307 the ST8SIA2 gene 1292:1307 the ST8SIA2 gene 1292:1307 15: 92998561 sites of the ST8SIA2 gene in ASD children were higher than those of controls. 35957920 1 11 theme membrane 205:212 arg1 alpha-2,8-sialyltransferase 147:173 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 106:175 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) 106:185 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 1 11 theme membrane 205:212 arg1 protein 214:220 a type II membrane protein 195:220 a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins 195:340 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 12 12 theme = 1464:1464 arg1 r 1462:1462 r 1462:1462 r = 0.41 1462:1469 15: 92984625 site was positively correlated with the stereotyped behaviors of ASD children (r = 0.41, p = 0.039). 35957920 4 13 theme control 620:626 arg1 children 628:635 76 normal control children 610:635 76 normal control children who were age- and sex-matched 610:665 Methods In this study, 69 ASD and 76 normal control children who were age- and sex-matched were recruited. 35957920 7 14 dep = 1098:1098 arg1 0.381 1100:1104 0.381 1100:1104 0.381 1100:1104 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 13 15 theme ST8SIA2 1576:1582 arg1 gene 1584:1587 the ST8SIA2 gene 1572:1587 the ST8SIA2 gene 1572:1587 Conclusion This study provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD. 35957920 5 16 theme children 862:869 arg1 phenotypes 844:853 the behavioral phenotypes 829:853 the behavioral phenotypes of ASD children 829:869 ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. 35957920 12 17 theme ASD 1448:1450 arg1 children 1452:1459 ASD children 1448:1459 ASD children 1448:1459 15: 92984625 site was positively correlated with the stereotyped behaviors of ASD children (r = 0.41, p = 0.039). 35957920 7 18 from behaviors 1161:1169 arg1 group 1182:1186 the ASD group 1174:1186 the ASD group (r = -0.510, p = 0.004) 1174:1210 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 7 19 theme ST8SIA2 1019:1025 arg1 levels 1038:1043 ST8SIA2 expression levels 1019:1043 ST8SIA2 expression levels 1019:1043 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 1 20 theme alpha-N-acetyl-neuraminide 120:145 arg1 alpha-2,8-sialyltransferase 147:173 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 106:175 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) 106:185 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 1 20 theme alpha-N-acetyl-neuraminide 120:145 arg1 ST8SIA2 178:184 ST8SIA2 178:184 ST8SIA2 178:184 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 1 20 theme alpha-N-acetyl-neuraminide 120:145 arg1 protein 214:220 a type II membrane protein 195:220 a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins 195:340 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 8 21 theme methylation 1217:1227 arg1 levels 1229:1234 The methylation levels 1213:1234 The methylation levels of the Chr 1213:1245 The methylation levels of the Chr. 35957920 5 22 theme ST8SIA2 683:689 arg1 expression 691:700 ST8SIA2 expression and methylation levels 683:723 expression 691:700 ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. 35957920 5 23 theme quantitative 764:775 arg1 PCR 787:789 reverse transcription quantitative real-time PCR 742:789 reverse transcription quantitative real-time PCR 742:789 ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. 35957920 6 24 theme p 997:997 arg1 0.011 1001:1005 0.05/2,143) = 2.582, p = 0.011 976:1005 0.011 1001:1005 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 6 24 theme p 997:997 arg1 group 966:970 the control group [t 954:973 the control group [t (0.05/2,143) = 2.582, p = 0.011] 954:1006 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 9 25 dep 92984625 1252:1259 arg1 15 1248:1249 15 1248:1249 15 1248:1249 15: 92984625 and Chr. 35957920 8 26 theme Chr 1243:1245 arg1 levels 1229:1234 The methylation levels 1213:1234 The methylation levels of the Chr 1213:1245 The methylation levels of the Chr. 35957920 6 27 theme 2.582 990:994 arg1 0.011 1001:1005 0.05/2,143) = 2.582, p = 0.011 976:1005 0.011 1001:1005 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 6 27 theme 2.582 990:994 arg1 group 966:970 the control group [t 954:973 the control group [t (0.05/2,143) = 2.582, p = 0.011] 954:1006 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 0 28 theme spectrum 87:94 arg1 disorder 96:103 autism spectrum disorder 80:103 autism spectrum disorder 80:103 The association between ST8SIA2 gene and behavioral phenotypes in children with autism spectrum disorder. 35957920 5 29 theme reverse 742:748 arg1 PCR 787:789 reverse transcription quantitative real-time PCR 742:789 reverse transcription quantitative real-time PCR 742:789 ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. 35957920 5 30 theme transcription 750:762 arg1 PCR 787:789 reverse transcription quantitative real-time PCR 742:789 reverse transcription quantitative real-time PCR 742:789 ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. 35957920 2 31 theme spectrum 444:451 arg1 disorder 453:460 the ST8SIA2 gene and autism spectrum disorder 416:460 the ST8SIA2 gene and autism spectrum disorder (ASD) 416:466 Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). 35957920 2 31 theme spectrum 444:451 arg1 ASD 463:465 ASD 463:465 ASD 463:465 Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). 35957920 5 32 theme behavioral 833:842 arg1 phenotypes 844:853 the behavioral phenotypes 829:853 the behavioral phenotypes of ASD children 829:869 ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. 35957920 1 33 theme Objective 106:114 arg1 alpha-2,8-sialyltransferase 147:173 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 106:175 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) 106:185 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 1 33 theme Objective 106:114 arg1 ST8SIA2 178:184 ST8SIA2 178:184 ST8SIA2 178:184 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 1 33 theme Objective 106:114 arg1 protein 214:220 a type II membrane protein 195:220 a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins 195:340 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 2 34 theme ST8SIA2 420:426 arg1 gene 428:431 ST8SIA2 gene 420:431 ST8SIA2 gene 420:431 Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). 35957920 2 35 theme population 348:357 arg1 studies 370:376 Some population and animal studies 343:376 studies 370:376 Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). 35957920 0 36 theme behavioral 41:50 arg1 phenotypes 52:61 behavioral phenotypes 41:61 behavioral phenotypes 41:61 The association between ST8SIA2 gene and behavioral phenotypes in children with autism spectrum disorder. 35957920 7 37 theme life 1083:1086 arg1 skills 1088:1093 daily life skills 1077:1093 daily life skills (r = 0.381, p = 0.008) 1077:1116 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 12 38 dep = 1474:1474 arg1 r 1462:1462 r 1462:1462 r = 0.41 1462:1469 15: 92984625 site was positively correlated with the stereotyped behaviors of ASD children (r = 0.41, p = 0.039). 35957920 10 39 from sites 1283:1287 arg1 children 1316:1323 ASD children 1312:1323 ASD children 1312:1323 15: 92998561 sites of the ST8SIA2 gene in ASD children were higher than those of controls. 35957920 6 40 theme expression 931:940 arg1 levels 942:947 lower ST8SIA2 gene expression levels 912:947 lower ST8SIA2 gene expression levels 912:947 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 7 41 dep skills 1088:1093 arg1 = 1109:1109 = 1109:1109 = 1109:1109 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 1 42 theme N-linked 298:305 arg1 oligosaccharides 307:322 N-linked oligosaccharides 298:322 N-linked oligosaccharides 298:322 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 4 43 from ASD 602:604 arg1 study 592:596 this study 587:596 this study 587:596 Methods In this study, 69 ASD and 76 normal control children who were age- and sex-matched were recruited. 35957920 2 44 theme animal 363:368 arg1 studies 370:376 Some population and animal studies 343:376 studies 370:376 Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). 35957920 6 45 theme ST8SIA2 918:924 arg1 levels 942:947 lower ST8SIA2 gene expression levels 912:947 lower ST8SIA2 gene expression levels 912:947 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 1 46 theme acid 273:276 arg1 transfer 254:261 the transfer 250:261 the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins 250:340 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 7 47 theme daily 1077:1081 arg1 skills 1088:1093 daily life skills 1077:1093 daily life skills (r = 0.381, p = 0.008) 1077:1116 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 1 48 gly glycoproteins 328:340 arg1 glycoproteins 328:340 glycoproteins 328:340 glycoproteins 328:340 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 6 49 theme ASD 898:900 arg1 group 902:906 The ASD group 894:906 The ASD group 894:906 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 13 50 theme behavioral 1593:1602 arg1 phenotypes 1604:1613 behavioral phenotypes 1593:1613 behavioral phenotypes 1593:1613 Conclusion This study provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD. 35957920 12 51 dep = 1464:1464 arg1 0.41 1466:1469 0.41 1466:1469 0.41 1466:1469 15: 92984625 site was positively correlated with the stereotyped behaviors of ASD children (r = 0.41, p = 0.039). 35957920 10 52 theme gene 1304:1307 arg1 sites 1283:1287 15: 92998561 sites 1270:1287 15: 92998561 sites of the ST8SIA2 gene in ASD children 1270:1323 15: 92998561 sites of the ST8SIA2 gene in ASD children were higher than those of controls. 35957920 10 52 theme gene 1304:1307 arg1 gene 1304:1307 the ST8SIA2 gene 1292:1307 the ST8SIA2 gene 1292:1307 15: 92998561 sites of the ST8SIA2 gene in ASD children were higher than those of controls. 35957920 3 53 theme behavioral 555:564 arg1 symptoms 566:573 autistic behavioral symptoms 546:573 autistic behavioral symptoms 546:573 However, there is limited information on the correlation between ST8SIA2 and autistic behavioral symptoms. 35957920 4 54 from children 628:635 arg1 study 592:596 this study 587:596 this study 587:596 Methods In this study, 69 ASD and 76 normal control children who were age- and sex-matched were recruited. 35957920 4 55 theme normal 613:618 arg1 children 628:635 76 normal control children 610:635 76 normal control children who were age- and sex-matched 610:665 Methods In this study, 69 ASD and 76 normal control children who were age- and sex-matched were recruited. 35957920 7 56 theme expression 1027:1036 arg1 levels 1038:1043 ST8SIA2 expression levels 1019:1043 ST8SIA2 expression levels 1019:1043 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 5 57 theme ASD 858:860 arg1 children 862:869 ASD children 858:869 ASD children 858:869 ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. 35957920 12 58 theme children 1452:1459 arg1 behaviors 1435:1443 the stereotyped behaviors 1419:1443 the stereotyped behaviors of ASD children 1419:1459 15: 92984625 site was positively correlated with the stereotyped behaviors of ASD children (r = 0.41, p = 0.039). 35957920 6 59 contain had 908:910 arg1 group 902:906 The ASD group 894:906 The ASD group 894:906 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 6 59 contain had 908:910 arg2 levels 942:947 lower ST8SIA2 gene expression levels 912:947 lower ST8SIA2 gene expression levels 912:947 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 1 60 theme ST8 116:118 arg1 alpha-2,8-sialyltransferase 147:173 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 106:175 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) 106:185 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 1 60 theme ST8 116:118 arg1 ST8SIA2 178:184 ST8SIA2 178:184 ST8SIA2 178:184 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 1 60 theme ST8 116:118 arg1 protein 214:220 a type II membrane protein 195:220 a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins 195:340 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 12 61 theme stereotyped 1423:1433 arg1 behaviors 1435:1443 the stereotyped behaviors 1419:1443 the stereotyped behaviors of ASD children 1419:1459 15: 92984625 site was positively correlated with the stereotyped behaviors of ASD children (r = 0.41, p = 0.039). 35957920 1 62 link N-linked 298:305 arg1 oligosaccharides 307:322 N-linked oligosaccharides 298:322 N-linked oligosaccharides 298:322 Objective ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. 35957920 7 63 theme ASD 1178:1180 arg1 group 1182:1186 the ASD group 1174:1186 the ASD group (r = -0.510, p = 0.004) 1174:1210 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 6 64 theme = 999:999 arg1 0.011 1001:1005 0.05/2,143) = 2.582, p = 0.011 976:1005 0.011 1001:1005 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 6 64 theme = 999:999 arg1 group 966:970 the control group [t 954:973 the control group [t (0.05/2,143) = 2.582, p = 0.011] 954:1006 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 13 65 theme ASD 1618:1620 arg1 gene 1584:1587 the ST8SIA2 gene 1572:1587 the ST8SIA2 gene 1572:1587 Conclusion This study provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD. 35957920 13 65 theme ASD 1618:1620 arg1 phenotypes 1604:1613 behavioral phenotypes 1593:1613 behavioral phenotypes 1593:1613 Conclusion This study provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD. 35957920 0 66 theme autism 80:85 arg1 disorder 96:103 autism spectrum disorder 80:103 autism spectrum disorder 80:103 The association between ST8SIA2 gene and behavioral phenotypes in children with autism spectrum disorder. 35957920 5 67 theme real-time 777:785 arg1 PCR 787:789 reverse transcription quantitative real-time PCR 742:789 reverse transcription quantitative real-time PCR 742:789 ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. 35957920 0 68 from association 4:14 arg1 children 66:73 children 66:73 children with autism spectrum disorder 66:103 The association between ST8SIA2 gene and behavioral phenotypes in children with autism spectrum disorder. 35957920 7 69 theme stereotyped 1149:1159 arg1 behaviors 1161:1169 stereotyped behaviors 1149:1169 stereotyped behaviors in the ASD group (r = -0.510, p = 0.004) 1149:1210 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 6 70 theme = 988:988 arg1 0.011 1001:1005 0.05/2,143) = 2.582, p = 0.011 976:1005 0.011 1001:1005 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 6 70 theme = 988:988 arg1 group 966:970 the control group [t 954:973 the control group [t (0.05/2,143) = 2.582, p = 0.011] 954:1006 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 10 71 theme ASD 1312:1314 arg1 children 1316:1323 ASD children 1312:1323 ASD children 1312:1323 15: 92998561 sites of the ST8SIA2 gene in ASD children were higher than those of controls. 35957920 7 72 dep = 1203:1203 arg1 r 1189:1189 r 1189:1189 r = -0.510 1189:1198 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 13 73 theme scientific 1517:1526 arg1 basis 1528:1532 a scientific basis 1515:1532 a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD 1515:1620 Conclusion This study provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD. 35957920 4 74 from Methods 576:582 arg1 study 592:596 this study 587:596 this study 587:596 Methods In this study, 69 ASD and 76 normal control children who were age- and sex-matched were recruited. 35957920 5 75 theme methylation 706:716 arg1 levels 718:723 ST8SIA2 expression and methylation levels 683:723 levels 718:723 ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. 35957920 7 76 dep = 1109:1109 arg1 r 1096:1096 r 1096:1096 r = 0.381 1096:1104 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 0 77 theme ST8SIA2 24:30 arg1 gene 32:35 ST8SIA2 gene 24:35 ST8SIA2 gene 24:35 The association between ST8SIA2 gene and behavioral phenotypes in children with autism spectrum disorder. 35957920 7 78 dep = 1191:1191 arg1 -0.510 1193:1198 -0.510 1193:1198 -0.510 1193:1198 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 2 79 theme autism 437:442 arg1 disorder 453:460 the ST8SIA2 gene and autism spectrum disorder 416:460 the ST8SIA2 gene and autism spectrum disorder (ASD) 416:466 Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). 35957920 2 79 theme autism 437:442 arg1 ASD 463:465 ASD 463:465 ASD 463:465 Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). 35957920 2 80 theme gene 428:431 arg1 disorder 453:460 the ST8SIA2 gene and autism spectrum disorder 416:460 the ST8SIA2 gene and autism spectrum disorder (ASD) 416:466 Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). 35957920 2 80 theme gene 428:431 arg1 ASD 463:465 ASD 463:465 ASD 463:465 Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). 35957920 7 81 dep group 1182:1186 arg1 = 1203:1203 = 1203:1203 = 1203:1203 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35957920 6 82 theme control 958:964 arg1 0.011 1001:1005 0.05/2,143) = 2.582, p = 0.011 976:1005 0.011 1001:1005 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 6 82 theme control 958:964 arg1 group 966:970 the control group [t 954:973 the control group [t (0.05/2,143) = 2.582, p = 0.011] 954:1006 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 6 83 dep Results 886:892 arg1 had 908:910 had 908:910 had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011] 908:1006 Results The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. 35957920 3 84 theme limited 487:493 arg1 information 495:505 limited information 487:505 limited information on the correlation between ST8SIA2 and autistic behavioral symptoms 487:573 However, there is limited information on the correlation between ST8SIA2 and autistic behavioral symptoms. 35957920 7 85 theme = 1191:1191 arg1 r 1189:1189 r 1189:1189 r = -0.510 1189:1198 Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r = -0.510, p = 0.004). 35311117 0 0 theme Nasopharyngeal 92:105 arg1 Carcinoma 107:115 Nasopharyngeal Carcinoma 92:115 Nasopharyngeal Carcinoma 92:115 TGF-β1-Mediated PD-L1 Glycosylation Contributes to Immune Escape via c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma. 35311117 7 1 theme advanced 1280:1287 arg1 stage 1298:1302 a more advanced clinical stage 1273:1302 a more advanced clinical stage 1273:1302 Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-β1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. 35311117 4 2 gly N-glycosylation 710:724 arg1 tissues 752:758 tissues 752:758 tissues 752:758 Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. 35311117 4 2 gly N-glycosylation 710:724 arg1 PD-L1 729:733 PD-L1 729:733 PD-L1 729:733 Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. 35311117 4 2 gly N-glycosylation 710:724 arg1 cells 742:746 NPC cells 738:746 NPC cells 738:746 Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. 35311117 2 3 theme protein 398:404 arg1 modification 376:387 post-translational modification 357:387 post-translational modification of PD-L1 protein 357:404 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 1 4 theme small 272:276 arg1 subset 278:283 only a small subset 265:283 only a small subset of patients 265:295 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 2 5 theme solid 541:545 arg1 tumors 547:552 several solid tumors 533:552 several solid tumors 533:552 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 9 6 theme TGF-β1 1542:1547 arg1 approach 1578:1585 a promising approach 1566:1585 a promising approach to enhance immune checkpoint blockade 1566:1623 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 9 6 theme TGF-β1 1542:1547 arg1 pathway 1549:1555 targeting TGF-β1 pathway 1532:1555 targeting TGF-β1 pathway 1532:1555 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 2 7 theme PD-L1 392:396 arg1 protein 398:404 PD-L1 protein 392:404 PD-L1 protein 392:404 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 9 8 theme promising 1568:1576 arg1 approach 1578:1585 a promising approach 1566:1585 a promising approach to enhance immune checkpoint blockade 1566:1623 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 9 8 theme promising 1568:1576 arg1 pathway 1549:1555 targeting TGF-β1 pathway 1532:1555 targeting TGF-β1 pathway 1532:1555 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 6 9 theme T-cell 1063:1068 arg1 function 1070:1077 cytotoxic T-cell function 1053:1077 cytotoxic T-cell function 1053:1077 Functional assays showed that inhibition of TGF-β1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. 35311117 2 10 with stability 433:441 arg1 PD-1 481:484 cognate receptor PD-1 464:484 cognate receptor PD-1 464:484 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 8 11 gly N-glycosylation 1375:1389 arg1 PD-L1 1394:1398 PD-L1 1394:1398 PD-L1 1394:1398 Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. 35311117 3 12 theme PD-1/PD-L1 604:613 arg1 expression 615:624 PD-1/PD-L1 expression 604:624 PD-1/PD-L1 expression 604:624 However, the molecular mechanisms underlying how PD-1/PD-L1 expression is regulated still remain unclear in nasopharyngeal carcinoma (NPC). 35311117 9 13 theme pathways 1672:1679 arg1 blockade 1643:1650 simultaneous blockade 1630:1650 simultaneous blockade of PD-L1 and TGF-β1 pathways 1630:1679 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 6 14 theme cytotoxic 1053:1061 arg1 function 1070:1077 cytotoxic T-cell function 1053:1077 cytotoxic T-cell function 1053:1077 Functional assays showed that inhibition of TGF-β1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. 35311117 9 15 theme PD-L1 1655:1659 arg1 blockade 1643:1650 simultaneous blockade 1630:1650 simultaneous blockade of PD-L1 and TGF-β1 pathways 1630:1679 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 9 16 theme simultaneous 1630:1641 arg1 blockade 1643:1650 simultaneous blockade 1630:1650 simultaneous blockade of PD-L1 and TGF-β1 pathways 1630:1679 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 8 17 theme immune 1427:1432 arg1 evasion 1434:1440 immune evasion 1427:1440 immune evasion 1427:1440 Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. 35311117 1 18 theme patients 288:295 arg1 subset 278:283 only a small subset 265:283 only a small subset of patients 265:295 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 2 19 with interaction 447:457 arg1 PD-1 481:484 cognate receptor PD-1 464:484 cognate receptor PD-1 464:484 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 8 20 theme c-Jun/STT3A 1334:1344 arg1 pathway 1356:1362 c-Jun/STT3A signaling pathway 1334:1362 c-Jun/STT3A signaling pathway 1334:1362 Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. 35311117 5 21 theme STT3A 928:932 arg1 promoter 934:941 STT3A promoter 928:941 STT3A promoter 928:941 Mechanistically, we showed that STT3A transferred N-linked glycans to PD-L1, and TGF-β1 could positively regulate STT3A expression through activating c-Jun to bind to STT3A promoter. 35311117 6 22 theme Functional 944:953 arg1 assays 955:960 Functional assays 944:960 Functional assays 944:960 Functional assays showed that inhibition of TGF-β1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. 35311117 2 23 theme several 533:539 arg1 tumors 547:552 several solid tumors 533:552 several solid tumors 533:552 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 9 24 theme immune 1598:1603 arg1 blockade 1616:1623 immune checkpoint blockade 1598:1623 immune checkpoint blockade 1598:1623 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 0 25 theme PD-L1 16:20 arg1 Glycosylation 22:34 TGF-β1-Mediated PD-L1 Glycosylation 0:34 TGF-β1-Mediated PD-L1 Glycosylation 0:34 TGF-β1-Mediated PD-L1 Glycosylation Contributes to Immune Escape via c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma. 35311117 7 26 theme clinical 1289:1296 arg1 stage 1298:1302 a more advanced clinical stage 1273:1302 a more advanced clinical stage 1273:1302 Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-β1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. 35311117 8 27 dep activated 1324:1332 arg1 reducing 1446:1453 reducing 1446:1453 reducing the efficacy of cancer immunotherapy 1446:1490 Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. 35311117 8 27 dep activated 1324:1332 arg1 facilitating 1414:1425 facilitating 1414:1425 further facilitating immune evasion 1406:1440 Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. 35311117 4 28 from N-glycosylation 710:724 arg1 tissues 752:758 tissues 752:758 tissues 752:758 Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. 35311117 4 28 from N-glycosylation 710:724 arg1 cells 742:746 NPC cells 738:746 NPC cells 738:746 Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. 35311117 2 29 theme protein 425:431 arg1 stability 433:441 its protein stability 421:441 its protein stability 421:441 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 0 30 theme TGF-β1-Mediated 0:14 arg1 Glycosylation 22:34 TGF-β1-Mediated PD-L1 Glycosylation 0:34 TGF-β1-Mediated PD-L1 Glycosylation 0:34 TGF-β1-Mediated PD-L1 Glycosylation Contributes to Immune Escape via c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma. 35311117 7 31 theme STT3A 1161:1165 arg1 expression 1147:1156 the expression 1143:1156 the expression of STT3A 1143:1165 Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-β1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. 35311117 1 32 theme great 226:230 arg1 success 232:238 great success 226:238 great success in multiple cancers 226:258 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 5 33 theme STT3A 875:879 arg1 expression 881:890 STT3A expression 875:890 STT3A expression 875:890 Mechanistically, we showed that STT3A transferred N-linked glycans to PD-L1, and TGF-β1 could positively regulate STT3A expression through activating c-Jun to bind to STT3A promoter. 35311117 1 34 theme clinical 304:311 arg1 responses 313:321 clinical responses 304:321 clinical responses 304:321 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 6 35 gly glycosylated 1021:1032 arg1 PD-L1 1034:1038 glycosylated PD-L1 1021:1038 glycosylated PD-L1 1021:1038 Functional assays showed that inhibition of TGF-β1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. 35311117 1 36 dep death 184:188 arg1 protein-1 190:198 protein-1 190:198 programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) 142:211 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 1 36 dep death 184:188 arg1 PD-L1/PD-1 201:210 PD-L1/PD-1 201:210 PD-L1/PD-1 201:210 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 9 37 theme targeting 1532:1540 arg1 approach 1578:1585 a promising approach 1566:1585 a promising approach to enhance immune checkpoint blockade 1566:1623 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 9 37 theme targeting 1532:1540 arg1 pathway 1549:1555 targeting TGF-β1 pathway 1532:1555 targeting TGF-β1 pathway 1532:1555 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 2 38 theme receptor 472:479 arg1 PD-1 481:484 cognate receptor PD-1 464:484 cognate receptor PD-1 464:484 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 6 39 theme glycosylated 1021:1032 arg1 PD-L1 1034:1038 glycosylated PD-L1 1021:1038 glycosylated PD-L1 1021:1038 Functional assays showed that inhibition of TGF-β1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. 35311117 2 40 theme Recent 324:329 arg1 evidences 331:339 Recent evidences 324:339 Recent evidences 324:339 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 2 41 theme cognate 464:470 arg1 PD-1 481:484 cognate receptor PD-1 464:484 cognate receptor PD-1 464:484 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 0 42 theme Immune 51:56 arg1 Escape 58:63 Immune Escape 51:63 Immune Escape 51:63 TGF-β1-Mediated PD-L1 Glycosylation Contributes to Immune Escape via c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma. 35311117 3 43 theme nasopharyngeal 663:676 arg1 NPC 689:691 NPC 689:691 NPC 689:691 However, the molecular mechanisms underlying how PD-1/PD-L1 expression is regulated still remain unclear in nasopharyngeal carcinoma (NPC). 35311117 3 43 theme nasopharyngeal 663:676 arg1 carcinoma 678:686 nasopharyngeal carcinoma 663:686 nasopharyngeal carcinoma (NPC) 663:692 However, the molecular mechanisms underlying how PD-1/PD-L1 expression is regulated still remain unclear in nasopharyngeal carcinoma (NPC). 35311117 4 44 theme PD-L1 729:733 arg1 N-glycosylation 710:724 N-glycosylation 710:724 N-glycosylation of PD-L1 in NPC cells and tissues 710:758 Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. 35311117 1 45 theme multiple 243:250 arg1 cancers 252:258 multiple cancers 243:258 multiple cancers 243:258 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 7 46 theme high 1220:1223 arg1 expression 1231:1240 high STT3A expression 1220:1240 high STT3A expression 1220:1240 Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-β1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. 35311117 0 47 from Pathway 81:87 arg1 Carcinoma 107:115 Nasopharyngeal Carcinoma 92:115 Nasopharyngeal Carcinoma 92:115 TGF-β1-Mediated PD-L1 Glycosylation Contributes to Immune Escape via c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma. 35311117 7 48 theme STT3A 1225:1229 arg1 expression 1231:1240 high STT3A expression 1220:1240 high STT3A expression 1220:1240 Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-β1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. 35311117 7 49 theme clinical 1110:1117 arg1 specimens 1119:1127 clinical specimens 1110:1127 clinical specimens 1110:1127 Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-β1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. 35311117 6 50 theme PD-L1 1034:1038 arg1 decrease 1009:1016 a decrease 1007:1016 a decrease of glycosylated PD-L1 1007:1038 Functional assays showed that inhibition of TGF-β1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. 35311117 9 51 theme potent 1694:1699 arg1 activity 1724:1731 potent and superior antitumor activity 1694:1731 potent and superior antitumor activity relative to monotherapies 1694:1757 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 9 52 theme checkpoint 1605:1614 arg1 blockade 1616:1623 immune checkpoint blockade 1598:1623 immune checkpoint blockade 1598:1623 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 1 53 theme programmed 142:151 arg1 death 184:188 programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) 142:211 programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) 142:211 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 2 54 theme anticancer 505:514 arg1 immunotherapy 516:528 anticancer immunotherapy 505:528 anticancer immunotherapy 505:528 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 7 55 theme specimens 1119:1127 arg1 Analysis 1098:1105 Analysis 1098:1105 Analysis of clinical specimens 1098:1127 Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-β1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. 35311117 1 56 from success 232:238 arg1 cancers 252:258 multiple cancers 243:258 multiple cancers 243:258 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 1 57 theme death 153:157 arg1 death 184:188 programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) 142:211 programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) 142:211 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 9 58 theme relative 1733:1740 arg1 activity 1724:1731 potent and superior antitumor activity 1694:1731 potent and superior antitumor activity relative to monotherapies 1694:1757 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 9 59 theme superior 1705:1712 arg1 activity 1724:1731 potent and superior antitumor activity 1694:1731 potent and superior antitumor activity relative to monotherapies 1694:1757 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 8 60 theme immunotherapy 1478:1490 arg1 efficacy 1459:1466 the efficacy 1455:1466 the efficacy of cancer immunotherapy 1455:1490 Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. 35311117 1 61 theme ligand-1/programmed 159:177 arg1 death 184:188 programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) 142:211 programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) 142:211 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 5 62 link N-linked 811:818 arg1 glycans 820:826 N-linked glycans 811:826 N-linked glycans 811:826 Mechanistically, we showed that STT3A transferred N-linked glycans to PD-L1, and TGF-β1 could positively regulate STT3A expression through activating c-Jun to bind to STT3A promoter. 35311117 9 63 theme antitumor 1714:1722 arg1 activity 1724:1731 potent and superior antitumor activity 1694:1731 potent and superior antitumor activity relative to monotherapies 1694:1757 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 1 64 theme cell 179:182 arg1 death 184:188 programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) 142:211 programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) 142:211 Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. 35311117 2 65 theme post-translational 357:374 arg1 modification 376:387 post-translational modification 357:387 post-translational modification of PD-L1 protein 357:404 Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. 35311117 5 66 theme N-linked 811:818 arg1 glycans 820:826 N-linked glycans 811:826 N-linked glycans 811:826 Mechanistically, we showed that STT3A transferred N-linked glycans to PD-L1, and TGF-β1 could positively regulate STT3A expression through activating c-Jun to bind to STT3A promoter. 35311117 8 67 theme cancer 1471:1476 arg1 immunotherapy 1478:1490 cancer immunotherapy 1471:1490 cancer immunotherapy 1471:1490 Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. 35311117 8 68 theme signaling 1346:1354 arg1 pathway 1356:1362 c-Jun/STT3A signaling pathway 1334:1362 c-Jun/STT3A signaling pathway 1334:1362 Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. 35311117 3 69 theme molecular 568:576 arg1 mechanisms 578:587 the molecular mechanisms 564:587 the molecular mechanisms underlying how PD-1/PD-L1 expression is regulated 564:637 However, the molecular mechanisms underlying how PD-1/PD-L1 expression is regulated still remain unclear in nasopharyngeal carcinoma (NPC). 35311117 8 70 theme PD-L1 1394:1398 arg1 N-glycosylation 1375:1389 N-glycosylation 1375:1389 N-glycosylation of PD-L1 1375:1398 Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. 35311117 6 71 theme NPC 1087:1089 arg1 cells 1091:1095 NPC cells 1087:1095 NPC cells 1087:1095 Functional assays showed that inhibition of TGF-β1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. 35311117 0 72 theme c-Jun/STT3A 69:79 arg1 Pathway 81:87 c-Jun/STT3A Pathway 69:87 c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma 69:115 TGF-β1-Mediated PD-L1 Glycosylation Contributes to Immune Escape via c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma. 35311117 6 73 theme TGF-β1 988:993 arg1 inhibition 974:983 inhibition 974:983 inhibition of TGF-β1 974:993 Functional assays showed that inhibition of TGF-β1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. 35311117 9 74 theme TGF-β1 1665:1670 arg1 pathways 1672:1679 TGF-β1 pathways 1665:1679 TGF-β1 pathways 1665:1679 As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies. 35311117 4 75 theme NPC 738:740 arg1 cells 742:746 NPC cells 738:746 NPC cells 738:746 Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. 37345806 0 0 theme Adaptive 74:81 arg1 responses 90:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses 36:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells 36:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 3 1 gly glycoproteins 738:750 arg1 glycoproteins 738:750 non-native glycoproteins 727:750 non-native glycoproteins 727:750 UGGT1 reglucosylates non-native glycoproteins and thereby allows them to revisit the ER folding machinery. 37345806 2 2 theme control 565:571 arg1 step 573:576 a quality control step 555:576 a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER) 555:703 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 2 3 theme MHC 529:531 arg1 complexes 535:543 MHC I complexes 529:543 MHC I complexes 529:543 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 4 4 theme I. 1012:1013 arg1 reglucosylation 989:1003 reglucosylation 989:1003 reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1 989:1165 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 4 4 theme I. 1012:1013 arg1 control 977:983 the UGGT1-catalyzed quality control 949:983 the UGGT1-catalyzed quality control 949:983 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 3 5 theme ER 791:792 arg1 machinery 802:810 the ER folding machinery 787:810 the ER folding machinery 787:810 UGGT1 reglucosylates non-native glycoproteins and thereby allows them to revisit the ER folding machinery. 37345806 0 6 theme I. 71:72 arg1 responses 90:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses 36:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells 36:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 2 7 theme quality 557:563 arg1 step 573:576 a quality control step 555:576 a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER) 555:703 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 3 8 theme folding 794:800 arg1 machinery 802:810 the ER folding machinery 787:810 the ER folding machinery 787:810 UGGT1 reglucosylates non-native glycoproteins and thereby allows them to revisit the ER folding machinery. 37345806 4 9 theme reconstituted 833:845 arg1 system 856:861 a reconstituted in-vitro system 831:861 a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1 831:1165 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 1 10 theme MHC 432:434 arg1 I 436:436 MHC I 432:436 MHC I 432:436 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 4 11 theme I 1156:1156 arg1 reglucosylation 1120:1134 reglucosylation 1120:1134 reglucosylation of peptide-free MHC I 1120:1156 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 4 12 theme TAPBPR 935:940 arg1 function 923:930 the function 919:930 the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1 919:1165 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 0 13 theme immune 83:88 arg1 responses 90:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses 36:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells 36:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 2 14 theme glycoproteins 657:669 arg1 status 623:628 the folding status 611:628 the folding status of the transiting N-linked glycoproteins 611:669 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 5 15 theme presentation 1296:1307 arg1 mechanisms 1259:1268 the quality control mechanisms 1239:1268 the quality control mechanisms of antigen processing and presentation 1239:1307 Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation. 37345806 1 16 theme related 340:346 arg1 chaperones 363:372 two related MHC I-specific chaperones 336:372 two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading 336:488 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 1 16 theme related 340:346 arg1 tapasin 316:322 tapasin 316:322 tapasin 316:322 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 0 17 theme pathogen-infected 216:232 arg1 cells 247:251 pathogen-infected or cancerous cells 216:251 pathogen-infected or cancerous cells 216:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 0 18 dep responses 90:98 arg1 triggered 104:112 triggered 104:112 are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells 100:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 1 19 theme MHC 348:350 arg1 chaperones 363:372 two related MHC I-specific chaperones 336:372 two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading 336:488 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 1 19 theme MHC 348:350 arg1 tapasin 316:322 tapasin 316:322 tapasin 316:322 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 0 20 theme cells 247:251 arg1 surface 205:211 the surface 201:211 the surface of pathogen-infected or cancerous cells 201:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 0 21 theme ER 4:5 arg1 UGGT1 22:26 The ER folding sensor UGGT1 0:26 The ER folding sensor UGGT1 0:26 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 1 22 theme I-specific 352:361 arg1 chaperones 363:372 two related MHC I-specific chaperones 336:372 two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading 336:488 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 1 22 theme I-specific 352:361 arg1 tapasin 316:322 tapasin 316:322 tapasin 316:322 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 4 23 dep reglucosylation 989:1003 arg1 show 1094:1097 show 1094:1097 show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1 1094:1165 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 0 24 theme cancerous 237:245 arg1 cells 247:251 pathogen-infected or cancerous cells 216:251 pathogen-infected or cancerous cells 216:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 4 25 theme in-vitro 847:854 arg1 system 856:861 a reconstituted in-vitro system 831:861 a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1 831:1165 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 5 26 theme processing 1281:1290 arg1 mechanisms 1259:1268 the quality control mechanisms 1239:1268 the quality control mechanisms of antigen processing and presentation 1239:1307 Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation. 37345806 0 27 theme sensor 15:20 arg1 UGGT1 22:26 The ER folding sensor UGGT1 0:26 The ER folding sensor UGGT1 0:26 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 1 28 theme stable 267:272 arg1 complexes 288:296 stable peptide-MHC I complexes 267:296 stable peptide-MHC I complexes 267:296 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 0 29 theme antigenic 117:125 arg1 peptides 127:134 antigenic peptides 117:134 antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells 117:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 1 30 theme peptide 458:464 arg1 editing 466:472 peptide editing 458:472 peptide editing 458:472 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 0 31 theme folding 7:13 arg1 UGGT1 22:26 The ER folding sensor UGGT1 0:26 The ER folding sensor UGGT1 0:26 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 1 32 theme peptide-MHC 274:284 arg1 complexes 288:296 stable peptide-MHC I complexes 267:296 stable peptide-MHC I complexes 267:296 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 4 33 theme human 875:879 arg1 proteins 881:888 purified human proteins 866:888 purified human proteins 866:888 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 5 34 theme quality 1243:1249 arg1 mechanisms 1259:1268 the quality control mechanisms 1239:1268 the quality control mechanisms of antigen processing and presentation 1239:1307 Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation. 37345806 4 35 theme UGGT1-catalyzed 953:967 arg1 control 977:983 the UGGT1-catalyzed quality control 949:983 the UGGT1-catalyzed quality control 949:983 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 1 36 theme I 286:286 arg1 complexes 288:296 stable peptide-MHC I complexes 267:296 stable peptide-MHC I complexes 267:296 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 2 37 theme cell 515:518 arg1 surface 520:526 the cell surface 511:526 the cell surface 511:526 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 5 38 theme antigen 1273:1279 arg1 processing 1281:1290 antigen processing 1273:1290 antigen processing 1273:1290 Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation. 37345806 5 39 theme control 1251:1257 arg1 mechanisms 1259:1268 the quality control mechanisms 1239:1268 the quality control mechanisms of antigen processing and presentation 1239:1307 Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation. 37345806 1 40 theme complexes 288:296 arg1 Formation 254:262 Formation 254:262 Formation of stable peptide-MHC I complexes 254:296 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 4 41 theme MHC 1008:1010 arg1 I. 1012:1013 MHC I. 1008:1013 MHC I. 1008:1013 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 3 42 theme non-native 727:736 arg1 glycoproteins 738:750 non-native glycoproteins 727:750 non-native glycoproteins 727:750 UGGT1 reglucosylates non-native glycoproteins and thereby allows them to revisit the ER folding machinery. 37345806 0 43 theme TAPBPR-chaperoned 36:52 arg1 responses 90:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses 36:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells 36:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 2 44 gly glycoproteins 657:669 arg1 glycoproteins 657:669 the transiting N-linked glycoproteins 633:669 the transiting N-linked glycoproteins 633:669 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 0 45 theme major 149:153 arg1 class 182:186 major histocompatibility complex class I 149:188 major histocompatibility complex class I (MHC I) 149:196 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 0 45 theme major 149:153 arg1 MHC 191:193 MHC I 191:195 MHC I 191:195 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 1 46 theme selective 388:396 arg1 loading 398:404 selective loading 388:404 selective loading of suitable peptides onto MHC I 388:436 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 2 47 theme I 533:533 arg1 complexes 535:543 MHC I complexes 529:543 MHC I complexes 529:543 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 4 48 theme quality 969:975 arg1 control 977:983 the UGGT1-catalyzed quality control 949:983 the UGGT1-catalyzed quality control 949:983 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 4 49 theme proteins 881:888 arg1 system 856:861 a reconstituted in-vitro system 831:861 a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1 831:1165 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 2 50 theme N-linked 648:655 arg1 glycoproteins 657:669 the transiting N-linked glycoproteins 633:669 the transiting N-linked glycoproteins 633:669 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 4 51 theme liquid 1050:1055 arg1 spectrometry 1077:1088 liquid chromatography-mass spectrometry 1050:1088 liquid chromatography-mass spectrometry 1050:1088 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 2 52 theme folding 615:621 arg1 status 623:628 the folding status 611:628 the folding status of the transiting N-linked glycoproteins 611:669 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 0 53 theme complex 174:180 arg1 class 182:186 major histocompatibility complex class I 149:188 major histocompatibility complex class I (MHC I) 149:196 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 0 53 theme complex 174:180 arg1 MHC 191:193 MHC I 191:195 MHC I 191:195 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 2 54 link N-linked 648:655 arg1 glycoproteins 657:669 the transiting N-linked glycoproteins 633:669 the transiting N-linked glycoproteins 633:669 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 2 55 theme transiting 637:646 arg1 glycoproteins 657:669 the transiting N-linked glycoproteins 633:669 the transiting N-linked glycoproteins 633:669 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 0 56 theme histocompatibility 155:172 arg1 class 182:186 major histocompatibility complex class I 149:188 major histocompatibility complex class I (MHC I) 149:196 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 0 56 theme histocompatibility 155:172 arg1 MHC 191:193 MHC I 191:195 MHC I 191:195 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 1 57 theme suitable 409:416 arg1 peptides 418:425 suitable peptides 409:425 suitable peptides 409:425 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 4 58 theme MHC 1152:1154 arg1 I 1156:1156 peptide-free MHC I 1139:1156 peptide-free MHC I 1139:1156 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 0 59 theme MHC 67:69 arg1 responses 90:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses 36:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells 36:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 1 60 theme peptides 418:425 arg1 loading 398:404 selective loading 388:404 selective loading of suitable peptides onto MHC I 388:436 Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. 37345806 4 61 theme peptide-free 1139:1150 arg1 I 1156:1156 peptide-free MHC I 1139:1156 peptide-free MHC I 1139:1156 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 4 62 theme chromatography-mass 1057:1075 arg1 spectrometry 1077:1088 liquid chromatography-mass spectrometry 1050:1088 liquid chromatography-mass spectrometry 1050:1088 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 4 63 theme purified 866:873 arg1 proteins 881:888 purified human proteins 866:888 purified human proteins 866:888 Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. 37345806 0 64 theme peptide-free 54:65 arg1 responses 90:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses 36:98 TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells 36:251 The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. 37345806 2 65 theme endoplasmic 678:688 arg1 ER 701:702 ER 701:702 ER 701:702 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 2 65 theme endoplasmic 678:688 arg1 reticulum 690:698 the endoplasmic reticulum 674:698 the endoplasmic reticulum (ER) 674:703 On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). 37345806 5 66 from function 1227:1234 arg1 mechanisms 1259:1268 the quality control mechanisms 1239:1268 the quality control mechanisms of antigen processing and presentation 1239:1307 Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation. 37345806 5 67 theme crucial 1219:1225 arg1 function 1227:1234 a crucial function 1217:1234 a crucial function in the quality control mechanisms of antigen processing and presentation 1217:1307 Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation. 35901192 3 0 theme N-glycosylation 659:673 arg1 90NDT92 695:701 90NDT92 695:701 90NDT92 695:701 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 0 theme N-glycosylation 659:673 arg1 75NIT77 683:689 75NIT77 683:689 75NIT77 683:689 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 0 theme N-glycosylation 659:673 arg1 motifs 675:680 the WHV precore/core N-glycosylation motifs 638:680 the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) 638:702 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 6 1 theme closed 1221:1226 arg1 cccDNA 1242:1247 cccDNA 1242:1247 cccDNA 1242:1247 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 1 theme closed 1221:1226 arg1 DNA 1237:1239 circular DNA 1228:1239 the covalently closed circular DNA (cccDNA) 1206:1248 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 1 theme closed 1221:1226 arg1 molecule 1274:1281 the critical viral DNA molecule 1251:1281 the critical viral DNA molecule responsible for establishing and maintaining infection 1251:1336 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 4 2 theme HBV 847:849 arg1 gene 864:867 the HBV precore/core gene 843:867 the HBV precore/core gene 843:867 Conversely, these N-glycosylation sequons were introduced into the HBV precore/core gene by E77T and N92T substitutions. 35901192 9 3 theme strong 1839:1844 arg1 constraints 1846:1856 strong constraints 1839:1856 strong constraints 1839:1856 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 3 4 from T77 623:625 arg1 90NDT92 695:701 90NDT92 695:701 90NDT92 695:701 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 4 from T77 623:625 arg1 75NIT77 683:689 75NIT77 683:689 75NIT77 683:689 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 4 from T77 623:625 arg1 motifs 675:680 the WHV precore/core N-glycosylation motifs 638:680 the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) 638:702 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 4 5 theme N-glycosylation 798:812 arg1 sequons 814:820 these N-glycosylation sequons 792:820 these N-glycosylation sequons 792:820 Conversely, these N-glycosylation sequons were introduced into the HBV precore/core gene by E77T and N92T substitutions. 35901192 3 6 from T92 631:633 arg1 90NDT92 695:701 90NDT92 695:701 90NDT92 695:701 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 6 from T92 631:633 arg1 75NIT77 683:689 75NIT77 683:689 75NIT77 683:689 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 6 from T92 631:633 arg1 motifs 675:680 the WHV precore/core N-glycosylation motifs 638:680 the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) 638:702 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 6 7 theme virion 1104:1109 arg1 secretion 1111:1119 virion secretion 1104:1119 virion secretion 1104:1119 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 9 8 theme host 1871:1874 arg1 adaptation 1876:1885 viral host adaptation 1865:1885 viral host adaptation resulting from their compact genome and extensive use of overlapping genes 1865:1960 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 3 9 theme HBV 727:729 arg1 E77 741:743 E77 741:743 E77 741:743 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 9 theme HBV 727:729 arg1 residues 731:738 the corresponding HBV residues 709:738 the corresponding HBV residues (E77 and N92) 709:752 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 9 theme HBV 727:729 arg1 N92 749:751 N92 749:751 N92 749:751 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 10 theme glycosylation 557:569 arg1 sites 571:575 the N-linked glycosylation sites 544:575 the N-linked glycosylation sites 544:575 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 5 11 from HBV 996:998 arg1 products 977:984 secreted precore gene products 955:984 secreted precore gene products from both HBV and WHV 955:1006 We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. 35901192 5 11 from HBV 996:998 arg1 levels 945:950 the levels 941:950 the levels of secreted precore gene products from both HBV and WHV 941:1006 We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. 35901192 1 12 theme coding 206:211 arg1 capacity 213:220 their coding capacity 200:220 their coding capacity 200:220 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 7 13 theme HBV 1572:1574 arg1 proteins 1585:1592 HBV envelope proteins 1572:1592 HBV envelope proteins for virion secretion 1572:1613 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 6 14 theme critical 1255:1262 arg1 DNA 1237:1239 circular DNA 1228:1239 the covalently closed circular DNA (cccDNA) 1206:1248 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 14 theme critical 1255:1262 arg1 molecule 1274:1281 the critical viral DNA molecule 1251:1281 the critical viral DNA molecule responsible for establishing and maintaining infection 1251:1336 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 4 15 gly N-glycosylation 798:812 arg2 sequons 814:820 these N-glycosylation sequons 792:820 these N-glycosylation sequons 792:820 Conversely, these N-glycosylation sequons were introduced into the HBV precore/core gene by E77T and N92T substitutions. 35901192 0 16 from Acquisition 69:79 arg1 genes 134:138 hepadnaviral precore/core genes 108:138 hepadnaviral precore/core genes 108:138 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 3 17 gly glycosylation 557:569 arg2 sites 571:575 the N-linked glycosylation sites 544:575 the N-linked glycosylation sites 544:575 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 9 18 theme extensive 1927:1935 arg1 use 1937:1939 extensive use 1927:1939 extensive use of overlapping genes 1927:1960 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 6 19 theme DNA 1237:1239 arg1 formation 1193:1201 the formation 1189:1201 the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection 1189:1336 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 7 20 dep HBc 1385:1387 arg1 proteins 1408:1415 core (WHc) proteins 1397:1415 core (WHc) proteins 1397:1415 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 6 21 contain carrying 1045:1052 arg1 protein 1037:1043 the HBV core (HBc) protein 1018:1043 the HBV core (HBc) protein carrying the E77T substitution 1018:1074 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 21 contain carrying 1045:1052 arg1 HBc 1032:1034 HBc 1032:1034 HBc 1032:1034 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 21 contain carrying 1045:1052 arg2 substitution 1063:1074 the E77T substitution 1054:1074 the E77T substitution 1054:1074 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 21 contain carrying 1045:1052 arg1 defective 1080:1088 defective 1080:1088 defective 1080:1088 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 3 22 link N-linked 548:555 arg1 sites 571:575 the N-linked glycosylation sites 544:575 the N-linked glycosylation sites 544:575 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 9 23 theme genes 1956:1960 arg1 genome 1916:1921 their compact genome 1902:1921 their compact genome 1902:1921 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 9 23 theme genes 1956:1960 arg1 use 1937:1939 extensive use 1927:1939 extensive use of overlapping genes 1927:1960 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 2 24 from precore 447:453 arg1 protein 362:368 The precore protein 350:368 The precore protein of the woodchuck hepatitis virus (WHV) 350:407 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 24 from precore 447:453 arg1 N-glycosylated 412:425 N-glycosylated 412:425 N-glycosylated 412:425 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 25 gly N-glycosylated 412:425 arg1 protein 362:368 The precore protein 350:368 The precore protein of the woodchuck hepatitis virus (WHV) 350:407 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 25 gly N-glycosylated 412:425 arg1 precore 447:453 the precore 443:453 the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation 443:517 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 25 gly N-glycosylated 412:425 arg2 N-glycosylated 412:425 N-glycosylated 412:425 N-glycosylated 412:425 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 25 gly N-glycosylated 412:425 arg1 N-glycosylated 412:425 N-glycosylated 412:425 N-glycosylated 412:425 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 25 gly N-glycosylated 412:425 arg2 protein 362:368 The precore protein 350:368 The precore protein of the woodchuck hepatitis virus (WHV) 350:407 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 3 26 from roles 535:539 arg1 functions 597:605 precore and core functions 580:605 functions 597:605 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 0 27 theme glycosylation 84:96 arg1 motifs 98:103 glycosylation motifs 84:103 glycosylation motifs in hepadnaviral precore/core genes 84:138 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 6 28 theme DNA 1270:1272 arg1 DNA 1237:1239 circular DNA 1228:1239 the covalently closed circular DNA (cccDNA) 1206:1248 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 28 theme DNA 1270:1272 arg1 molecule 1274:1281 the critical viral DNA molecule 1251:1281 the critical viral DNA molecule responsible for establishing and maintaining infection 1251:1336 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 29 theme core 1026:1029 arg1 protein 1037:1043 the HBV core (HBc) protein 1018:1043 the HBV core (HBc) protein carrying the E77T substitution 1018:1074 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 29 theme core 1026:1029 arg1 HBc 1032:1034 HBc 1032:1034 HBc 1032:1034 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 29 theme core 1026:1029 arg1 defective 1080:1088 defective 1080:1088 defective 1080:1088 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 0 30 theme Constrained 0:10 arg1 evolution 12:20 Constrained evolution 0:20 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 0:139 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 2 31 dep precore 447:453 arg1 contrast 431:438 contrast 431:438 contrast 431:438 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 0 32 dep evolution 12:20 arg1 Acquisition 69:79 Acquisition 69:79 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 0:139 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 1 33 theme identical 306:314 arg1 sequences 316:324 mostly identical sequences 299:324 mostly identical sequences 299:324 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 7 34 theme envelope 1576:1583 arg1 proteins 1585:1592 HBV envelope proteins 1572:1592 HBV envelope proteins for virion secretion 1572:1613 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 2 35 theme B 478:478 arg1 HBV 487:489 HBV 487:489 HBV 487:489 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 35 theme B 478:478 arg1 virus 480:484 the human hepatitis B virus 458:484 the human hepatitis B virus (HBV) that lacks N-glycosylation 458:517 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 0 36 theme genes 37:41 arg1 evolution 12:20 Constrained evolution 0:20 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 0:139 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 9 37 theme novel 1765:1769 arg1 determinants 1771:1782 novel determinants 1765:1782 novel determinants of precore secretion and core functions 1765:1822 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 7 38 theme replication 1454:1464 arg1 steps 1431:1435 all steps 1427:1435 all steps of intracellular replication of the heterologous virus 1427:1490 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 2 39 theme human 462:466 arg1 HBV 487:489 HBV 487:489 HBV 487:489 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 39 theme human 462:466 arg1 virus 480:484 the human hepatitis B virus 458:484 the human hepatitis B virus (HBV) that lacks N-glycosylation 458:517 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 0 40 theme viral 46:50 arg1 adaptation 57:66 viral host adaptation 46:66 viral host adaptation 46:66 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 9 41 theme precore 1787:1793 arg1 secretion 1795:1803 precore secretion 1787:1803 precore secretion 1787:1803 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 3 42 gly N-glycosylation 659:673 arg2 90NDT92 695:701 90NDT92 695:701 90NDT92 695:701 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 42 gly N-glycosylation 659:673 arg2 75NIT77 683:689 75NIT77 683:689 75NIT77 683:689 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 42 gly N-glycosylation 659:673 arg2 motifs 675:680 the WHV precore/core N-glycosylation motifs 638:680 the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) 638:702 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 43 theme precore/core 646:657 arg1 90NDT92 695:701 90NDT92 695:701 90NDT92 695:701 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 43 theme precore/core 646:657 arg1 75NIT77 683:689 75NIT77 683:689 75NIT77 683:689 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 43 theme precore/core 646:657 arg1 motifs 675:680 the WHV precore/core N-glycosylation motifs 638:680 the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) 638:702 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 2 44 theme precore 354:360 arg1 protein 362:368 The precore protein 350:368 The precore protein of the woodchuck hepatitis virus (WHV) 350:407 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 44 theme precore 354:360 arg1 N-glycosylated 412:425 N-glycosylated 412:425 N-glycosylated 412:425 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 1 45 theme precore/core 238:249 arg1 genes 251:255 especially the precore/core genes 223:255 especially the precore/core genes 223:255 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 1 45 theme precore/core 238:249 arg1 proteins 285:292 the precore and core proteins 264:292 proteins 285:292 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 5 46 theme precore 964:970 arg1 products 977:984 secreted precore gene products 955:984 secreted precore gene products from both HBV and WHV 955:1006 We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. 35901192 2 47 theme virus 397:401 arg1 protein 362:368 The precore protein 350:368 The precore protein of the woodchuck hepatitis virus (WHV) 350:407 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 47 theme virus 397:401 arg1 N-glycosylated 412:425 N-glycosylated 412:425 N-glycosylated 412:425 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 5 48 theme products 977:984 arg1 levels 945:950 the levels 941:950 the levels of secreted precore gene products from both HBV and WHV 941:1006 We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. 35901192 9 49 theme functions 1814:1822 arg1 determinants 1771:1782 novel determinants 1765:1782 novel determinants of precore secretion and core functions 1765:1822 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 6 50 theme circular 1228:1235 arg1 cccDNA 1242:1247 cccDNA 1242:1247 cccDNA 1242:1247 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 50 theme circular 1228:1235 arg1 DNA 1237:1239 circular DNA 1228:1239 the covalently closed circular DNA (cccDNA) 1206:1248 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 50 theme circular 1228:1235 arg1 molecule 1274:1281 the critical viral DNA molecule 1251:1281 the critical viral DNA molecule responsible for establishing and maintaining infection 1251:1336 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 2 51 theme woodchuck 377:385 arg1 WHV 404:406 WHV 404:406 WHV 404:406 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 51 theme woodchuck 377:385 arg1 virus 397:401 the woodchuck hepatitis virus 373:401 the woodchuck hepatitis virus (WHV) 373:407 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 1 52 theme precore 268:274 arg1 genes 251:255 especially the precore/core genes 223:255 especially the precore/core genes 223:255 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 1 52 theme precore 268:274 arg1 proteins 285:292 the precore and core proteins 264:292 proteins 285:292 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 7 53 theme WHc 1403:1405 arg1 proteins 1408:1415 core (WHc) proteins 1397:1415 core (WHc) proteins 1397:1415 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 1 54 theme core 280:283 arg1 genes 251:255 especially the precore/core genes 223:255 especially the precore/core genes 223:255 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 1 54 theme core 280:283 arg1 proteins 285:292 the precore and core proteins 264:292 proteins 285:292 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 7 55 theme cross-species 1342:1354 arg1 assays 1372:1377 cross-species complementation assays 1342:1377 cross-species complementation assays 1342:1377 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 7 56 theme core 1397:1400 arg1 proteins 1408:1415 core (WHc) proteins 1397:1415 core (WHc) proteins 1397:1415 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 9 57 theme viral 1865:1869 arg1 adaptation 1876:1885 viral host adaptation 1865:1885 viral host adaptation resulting from their compact genome and extensive use of overlapping genes 1865:1960 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 3 58 theme N-linked 548:555 arg1 sites 571:575 the N-linked glycosylation sites 544:575 the N-linked glycosylation sites 544:575 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 7 59 theme complementation 1356:1370 arg1 assays 1372:1377 cross-species complementation assays 1342:1377 cross-species complementation assays 1342:1377 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 6 60 theme viral 1264:1268 arg1 DNA 1237:1239 circular DNA 1228:1239 the covalently closed circular DNA (cccDNA) 1206:1248 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 60 theme viral 1264:1268 arg1 molecule 1274:1281 the critical viral DNA molecule 1251:1281 the critical viral DNA molecule responsible for establishing and maintaining infection 1251:1336 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 3 61 with T77 623:625 arg1 E77 741:743 E77 741:743 E77 741:743 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 61 with T77 623:625 arg1 residues 731:738 the corresponding HBV residues 709:738 the corresponding HBV residues (E77 and N92) 709:752 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 61 with T77 623:625 arg1 N92 749:751 N92 749:751 N92 749:751 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 8 62 theme cccDNA 1676:1681 arg1 amplification 1683:1695 intracellular cccDNA amplification 1662:1695 intracellular cccDNA amplification 1662:1695 Interestingly, WHc supported more efficiently intracellular cccDNA amplification than HBc in the context of either HBV or WHV. 35901192 3 63 theme corresponding 713:725 arg1 E77 741:743 E77 741:743 E77 741:743 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 63 theme corresponding 713:725 arg1 residues 731:738 the corresponding HBV residues 709:738 the corresponding HBV residues (E77 and N92) 709:752 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 63 theme corresponding 713:725 arg1 N92 749:751 N92 749:751 N92 749:751 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 64 theme precore 580:586 arg1 functions 597:605 precore and core functions 580:605 functions 597:605 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 65 with T92 631:633 arg1 E77 741:743 E77 741:743 E77 741:743 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 65 with T92 631:633 arg1 residues 731:738 the corresponding HBV residues 709:738 the corresponding HBV residues (E77 and N92) 709:752 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 65 with T92 631:633 arg1 N92 749:751 N92 749:751 N92 749:751 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 6 66 theme N92T 1161:1164 arg1 substitutions 1166:1178 the HBc E77T and N92T substitutions 1144:1178 the HBc E77T and N92T substitutions 1144:1178 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 9 67 theme compact 1908:1914 arg1 genome 1916:1921 their compact genome 1902:1921 their compact genome 1902:1921 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 3 68 theme sites 571:575 arg1 roles 535:539 the roles 531:539 the roles of the N-linked glycosylation sites in precore and core functions 531:605 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 7 69 theme N-glycosylation 1523:1537 arg1 sequons 1539:1545 the N-glycosylation sequons 1519:1545 the N-glycosylation sequons 1519:1545 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 4 70 theme precore/core 851:862 arg1 gene 864:867 the HBV precore/core gene 843:867 the HBV precore/core gene 843:867 Conversely, these N-glycosylation sequons were introduced into the HBV precore/core gene by E77T and N92T substitutions. 35901192 6 71 theme E77T 1152:1155 arg1 substitutions 1166:1178 the HBc E77T and N92T substitutions 1144:1178 the HBc E77T and N92T substitutions 1144:1178 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 0 72 from motifs 98:103 arg1 genes 134:138 hepadnaviral precore/core genes 108:138 hepadnaviral precore/core genes 108:138 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 8 73 theme intracellular 1662:1674 arg1 amplification 1683:1695 intracellular cccDNA amplification 1662:1695 intracellular cccDNA amplification 1662:1695 Interestingly, WHc supported more efficiently intracellular cccDNA amplification than HBc in the context of either HBV or WHV. 35901192 4 74 dep E77T 872:875 arg1 substitutions 886:898 substitutions 886:898 substitutions 886:898 Conversely, these N-glycosylation sequons were introduced into the HBV precore/core gene by E77T and N92T substitutions. 35901192 3 75 theme core 592:595 arg1 functions 597:605 precore and core functions 580:605 functions 597:605 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 9 76 theme overlapping 1944:1954 arg1 genes 1956:1960 overlapping genes 1944:1960 overlapping genes 1944:1960 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 6 77 theme responsible 1283:1293 arg1 DNA 1237:1239 circular DNA 1228:1239 the covalently closed circular DNA (cccDNA) 1206:1248 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 77 theme responsible 1283:1293 arg1 molecule 1274:1281 the critical viral DNA molecule 1251:1281 the critical viral DNA molecule responsible for establishing and maintaining infection 1251:1336 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 5 78 from WHV 1004:1006 arg1 products 977:984 secreted precore gene products 955:984 secreted precore gene products from both HBV and WHV 955:1006 We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. 35901192 5 78 from WHV 1004:1006 arg1 levels 945:950 the levels 941:950 the levels of secreted precore gene products from both HBV and WHV 941:1006 We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. 35901192 8 79 theme HBV 1731:1733 arg1 context 1713:1719 the context 1709:1719 the context of either HBV or WHV 1709:1740 Interestingly, WHc supported more efficiently intracellular cccDNA amplification than HBc in the context of either HBV or WHV. 35901192 1 80 theme overlapping 172:182 arg1 genes 184:188 extensively overlapping genes 160:188 extensively overlapping genes 160:188 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 2 81 theme virus 480:484 arg1 precore 447:453 the precore 443:453 the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation 443:517 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 0 82 from evolution 12:20 arg1 adaptation 57:66 viral host adaptation 46:66 viral host adaptation 46:66 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 0 83 theme motifs 98:103 arg1 Acquisition 69:79 Acquisition 69:79 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 0:139 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 3 84 dep residues 731:738 arg1 E77 741:743 E77 741:743 E77 741:743 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 84 dep residues 731:738 arg1 residues 731:738 the corresponding HBV residues 709:738 the corresponding HBV residues (E77 and N92) 709:752 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 84 dep residues 731:738 arg1 N92 749:751 N92 749:751 N92 749:751 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 8 85 theme WHV 1738:1740 arg1 context 1713:1719 the context 1709:1719 the context of either HBV or WHV 1709:1740 Interestingly, WHc supported more efficiently intracellular cccDNA amplification than HBc in the context of either HBV or WHV. 35901192 7 86 theme virus 1486:1490 arg1 replication 1454:1464 intracellular replication 1440:1464 intracellular replication of the heterologous virus 1440:1490 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 0 87 theme hepadnaviral 108:119 arg1 genes 134:138 hepadnaviral precore/core genes 108:138 hepadnaviral precore/core genes 108:138 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 0 88 gly glycosylation 84:96 arg2 motifs 98:103 glycosylation motifs 84:103 glycosylation motifs in hepadnaviral precore/core genes 84:138 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 6 89 theme HBV 1022:1024 arg1 protein 1037:1043 the HBV core (HBc) protein 1018:1043 the HBV core (HBc) protein carrying the E77T substitution 1018:1074 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 89 theme HBV 1022:1024 arg1 HBc 1032:1034 HBc 1032:1034 HBc 1032:1034 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 6 89 theme HBV 1022:1024 arg1 defective 1080:1088 defective 1080:1088 defective 1080:1088 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 0 90 theme overlapping 25:35 arg1 genes 37:41 overlapping genes 25:41 overlapping genes 25:41 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 3 91 dep motifs 675:680 arg1 90NDT92 695:701 90NDT92 695:701 90NDT92 695:701 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 91 dep motifs 675:680 arg1 75NIT77 683:689 75NIT77 683:689 75NIT77 683:689 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 91 dep motifs 675:680 arg1 motifs 675:680 the WHV precore/core N-glycosylation motifs 638:680 the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) 638:702 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 7 92 theme virion 1598:1603 arg1 secretion 1605:1613 virion secretion 1598:1613 virion secretion 1598:1613 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 7 93 theme heterologous 1473:1484 arg1 virus 1486:1490 the heterologous virus 1469:1490 the heterologous virus 1469:1490 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 2 94 theme hepatitis 468:476 arg1 HBV 487:489 HBV 487:489 HBV 487:489 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 94 theme hepatitis 468:476 arg1 virus 480:484 the human hepatitis B virus 458:484 the human hepatitis B virus (HBV) that lacks N-glycosylation 458:517 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 0 95 theme host 52:55 arg1 adaptation 57:66 viral host adaptation 46:66 viral host adaptation 46:66 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 1 96 theme distinct 330:337 arg1 functions 339:347 distinct functions 330:347 distinct functions 330:347 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 1 97 with proteins 285:292 arg1 sequences 316:324 mostly identical sequences 299:324 mostly identical sequences 299:324 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 1 97 with proteins 285:292 arg1 functions 339:347 distinct functions 330:347 distinct functions 330:347 Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. 35901192 3 98 theme WHV 642:644 arg1 90NDT92 695:701 90NDT92 695:701 90NDT92 695:701 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 98 theme WHV 642:644 arg1 75NIT77 683:689 75NIT77 683:689 75NIT77 683:689 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 3 98 theme WHV 642:644 arg1 motifs 675:680 the WHV precore/core N-glycosylation motifs 638:680 the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) 638:702 To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. 35901192 7 99 theme intracellular 1440:1452 arg1 replication 1454:1464 intracellular replication 1440:1464 intracellular replication of the heterologous virus 1440:1490 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 5 100 theme secreted 955:962 arg1 products 977:984 secreted precore gene products 955:984 secreted precore gene products from both HBV and WHV 955:1006 We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. 35901192 7 101 gly N-glycosylation 1523:1537 arg2 sequons 1539:1545 the N-glycosylation sequons 1519:1545 the N-glycosylation sequons 1519:1545 In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. 35901192 6 102 theme E77T 1058:1061 arg1 substitution 1063:1074 the E77T substitution 1054:1074 the E77T substitution 1054:1074 However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. 35901192 9 103 theme secretion 1795:1803 arg1 determinants 1771:1782 novel determinants 1765:1782 novel determinants of precore secretion and core functions 1765:1822 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 5 104 theme gene 972:975 arg1 products 977:984 secreted precore gene products 955:984 secreted precore gene products from both HBV and WHV 955:1006 We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. 35901192 2 105 from N-glycosylated 412:425 arg1 precore 447:453 the precore 443:453 the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation 443:517 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 0 106 theme precore/core 121:132 arg1 genes 134:138 hepadnaviral precore/core genes 108:138 hepadnaviral precore/core genes 108:138 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 9 107 theme core 1809:1812 arg1 functions 1814:1822 core functions 1809:1822 core functions 1809:1822 These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes. 35901192 0 108 from genes 134:138 arg1 Acquisition 69:79 Acquisition 69:79 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 0:139 Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes. 35901192 2 109 theme hepatitis 387:395 arg1 WHV 404:406 WHV 404:406 WHV 404:406 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 2 109 theme hepatitis 387:395 arg1 virus 397:401 the woodchuck hepatitis virus 373:401 the woodchuck hepatitis virus (WHV) 373:407 The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. 35901192 5 110 from levels 945:950 arg1 WHV 1004:1006 WHV 1004:1006 WHV 1004:1006 We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. 35901192 5 110 from levels 945:950 arg1 HBV 996:998 HBV 996:998 HBV 996:998 We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. 37005916 13 0 theme parameters 2805:2814 arg1 series 2782:2787 a series 2780:2787 a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ) 2780:2972 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 10 1 theme assisted 2003:2010 arg1 effervescence 1978:1990 effervescence 1978:1990 effervescence 1978:1990 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 10 1 theme assisted 2003:2010 arg1 method 2012:2017 a novel assisted method 1995:2017 a novel assisted method for the dispersion of solvents or adsorbents 1995:2062 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 11 2 theme elution 2477:2483 arg1 time 2485:2488 the elution time 2473:2488 the elution time 2473:2488 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 17 3 theme dairy 3820:3824 arg1 beverages 3843:3851 beverages 3843:3851 beverages 3843:3851 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 17 3 theme dairy 3820:3824 arg1 blood 3881:3885 blood 3881:3885 blood 3881:3885 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 17 3 theme dairy 3820:3824 arg1 urine 3888:3892 urine 3888:3892 urine 3888:3892 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 17 3 theme dairy 3820:3824 arg1 products 3826:3833 dairy products 3820:3833 dairy products 3820:3833 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 17 3 theme dairy 3820:3824 arg1 botanicals 3914:3923 complex botanicals 3906:3923 complex botanicals 3906:3923 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 17 3 theme dairy 3820:3824 arg1 water 3862:3866 surface water 3854:3866 surface water 3854:3866 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 17 3 theme dairy 3820:3824 arg1 vegetables 3869:3878 vegetables 3869:3878 vegetables 3869:3878 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 17 3 theme dairy 3820:3824 arg1 liver 3895:3899 liver 3895:3899 liver 3895:3899 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 17 3 theme dairy 3820:3824 arg1 honey 3836:3840 honey 3836:3840 honey 3836:3840 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 16 4 theme analytical 3659:3668 arg1 techniques 3670:3679 other analytical techniques 3653:3679 other analytical techniques 3653:3679 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 10 5 theme pyrethyl 2140:2147 arg1 pesticides 2149:2158 the pyrethyl pesticides 2136:2158 the pyrethyl pesticides 2136:2158 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 9 6 theme absorption 1819:1828 arg1 AAS 1844:1846 AAS 1844:1846 AAS 1844:1846 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 9 6 theme absorption 1819:1828 arg1 spectroscopy 1830:1841 atomic absorption spectroscopy 1812:1841 atomic absorption spectroscopy (AAS) 1812:1847 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 11 7 theme tablet 2334:2339 arg1 type 2431:2434 the type 2427:2434 the type of eluent 2427:2444 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 7 theme tablet 2334:2339 arg1 mass/volume 2400:2410 mass/volume 2400:2410 mass/volume 2400:2410 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 7 theme tablet 2334:2339 arg1 temperature 2374:2384 the extraction temperature 2359:2384 the extraction temperature 2359:2384 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 7 theme tablet 2334:2339 arg1 performance 2512:2522 the regeneration performance 2495:2522 the regeneration performance 2495:2522 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 7 theme tablet 2334:2339 arg1 time 2485:2488 the elution time 2473:2488 the elution time 2473:2488 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 7 theme tablet 2334:2339 arg1 pH 2355:2356 the solution pH 2342:2356 the solution pH 2342:2356 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 7 theme tablet 2334:2339 arg1 composition 2302:2312 the composition 2298:2312 the composition of the effervescent tablet 2298:2339 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 7 theme tablet 2334:2339 arg1 concentration 2458:2470 the eluent concentration 2447:2470 the eluent concentration 2447:2470 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 7 theme tablet 2334:2339 arg1 type 2391:2394 the type 2387:2394 the type 2387:2394 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 1 8 theme rapid 269:273 arg1 dispersion 275:284 rapid dispersion 269:284 rapid dispersion of the extractant 269:302 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 15 9 theme EAM 3292:3294 arg1 method 3296:3301 an EAM method 3289:3301 an EAM method based on nanomaterials, ionic liquids, and other emerging extractants 3289:3371 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 7 10 theme other 1436:1440 arg1 substrates 1454:1463 other interfering substrates 1436:1463 other interfering substrates 1436:1463 However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. 37005916 19 11 theme various 4147:4153 arg1 pollutants 4155:4164 various pollutants 4147:4164 various pollutants 4147:4164 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 6 12 theme target 1238:1243 arg1 samples 1326:1332 food, plant, biological, and environmental samples 1283:1332 food, plant, biological, and environmental samples 1283:1332 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 6 12 theme target 1238:1243 arg1 compounds 1245:1253 target compounds 1238:1253 target compounds 1238:1253 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 10 13 theme adsorbents 2053:2062 arg1 dispersion 2027:2036 the dispersion 2023:2036 the dispersion of solvents or adsorbents 2023:2062 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 1 14 theme CO2 215:217 arg1 donors 226:231 CO2 and H+ donors 215:231 CO2 and H+ donors 215:231 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 15 15 theme other 3346:3350 arg1 extractants 3361:3371 other emerging extractants 3346:3371 other emerging extractants 3346:3371 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 12 16 theme optimization 2595:2606 arg1 methods 2608:2614 the cumbersome single factor optimization and multi-factor optimization methods 2536:2614 the cumbersome single factor optimization and multi-factor optimization methods 2536:2614 Generally, the cumbersome single factor optimization and multi-factor optimization methods are also required to determine the optimal experimental conditions. 37005916 10 17 theme novel 1997:2001 arg1 effervescence 1978:1990 effervescence 1978:1990 effervescence 1978:1990 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 10 17 theme novel 1997:2001 arg1 method 2012:2017 a novel assisted method 1995:2017 a novel assisted method for the dispersion of solvents or adsorbents 1995:2062 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 10 18 theme solvents 2041:2048 arg1 dispersion 2027:2036 the dispersion 2023:2036 the dispersion of solvents or adsorbents 2023:2062 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 6 19 theme biological 1296:1305 arg1 food 1283:1286 food 1283:1286 food 1283:1286 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 13 20 theme EAM 2752:2754 arg1 method 2756:2761 the EAM method 2748:2761 the EAM method 2748:2761 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 1 21 theme H+ 223:224 arg1 donors 226:231 CO2 and H+ donors 215:231 CO2 and H+ donors 215:231 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 16 22 theme cold 3633:3636 arg1 AAS 3644:3646 cold flame AAS 3633:3646 cold flame AAS 3633:3646 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 12 23 theme cumbersome 2540:2549 arg1 optimization 2565:2576 cumbersome single factor optimization 2540:2576 cumbersome single factor optimization 2540:2576 Generally, the cumbersome single factor optimization and multi-factor optimization methods are also required to determine the optimal experimental conditions. 37005916 16 24 from state-of-the-art 3547:3562 arg1 relation 3567:3574 relation 3567:3574 relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques 3567:3679 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 9 25 theme heavy 1878:1882 arg1 ions 1890:1893 heavy metal ions 1878:1893 heavy metal ions 1878:1893 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 19 26 theme monitoring 4219:4228 arg1 pollutants 4230:4239 monitoring pollutants 4219:4239 monitoring pollutants 4219:4239 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 6 27 theme plant 1289:1293 arg1 samples 1326:1332 food, plant, biological, and environmental samples 1283:1332 food, plant, biological, and environmental samples 1283:1332 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 11 28 theme method 2268:2273 arg1 development 2275:2285 method development 2268:2285 method development 2268:2285 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 18 29 from trend 4033:4037 arg1 field 4046:4050 the field 4042:4050 the field of microextraction 4042:4069 Furthermore, issues related to the application of this technology are analyzed, and its future development trend in the field of microextraction is forecasted. 37005916 12 30 theme optimal 2651:2657 arg1 conditions 2672:2681 the optimal experimental conditions 2647:2681 the optimal experimental conditions 2647:2681 Generally, the cumbersome single factor optimization and multi-factor optimization methods are also required to determine the optimal experimental conditions. 37005916 12 31 theme factor 2558:2563 arg1 optimization 2565:2576 cumbersome single factor optimization 2540:2576 cumbersome single factor optimization 2540:2576 Generally, the cumbersome single factor optimization and multi-factor optimization methods are also required to determine the optimal experimental conditions. 37005916 11 32 theme eluent 2439:2444 arg1 type 2431:2434 the type 2427:2434 the type of eluent 2427:2444 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 32 theme eluent 2439:2444 arg1 mass/volume 2400:2410 mass/volume 2400:2410 mass/volume 2400:2410 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 32 theme eluent 2439:2444 arg1 temperature 2374:2384 the extraction temperature 2359:2384 the extraction temperature 2359:2384 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 32 theme eluent 2439:2444 arg1 performance 2512:2522 the regeneration performance 2495:2522 the regeneration performance 2495:2522 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 32 theme eluent 2439:2444 arg1 time 2485:2488 the elution time 2473:2488 the elution time 2473:2488 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 32 theme eluent 2439:2444 arg1 pH 2355:2356 the solution pH 2342:2356 the solution pH 2342:2356 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 32 theme eluent 2439:2444 arg1 composition 2302:2312 the composition 2298:2312 the composition of the effervescent tablet 2298:2339 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 32 theme eluent 2439:2444 arg1 concentration 2458:2470 the eluent concentration 2447:2470 the eluent concentration 2447:2470 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 32 theme eluent 2439:2444 arg1 type 2391:2394 the type 2387:2394 the type 2387:2394 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 6 33 theme food 1283:1286 arg1 samples 1326:1332 food, plant, biological, and environmental samples 1283:1332 food, plant, biological, and environmental samples 1283:1332 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 12 34 theme optimization 2565:2576 arg1 methods 2608:2614 the cumbersome single factor optimization and multi-factor optimization methods 2536:2614 the cumbersome single factor optimization and multi-factor optimization methods 2536:2614 Generally, the cumbersome single factor optimization and multi-factor optimization methods are also required to determine the optimal experimental conditions. 37005916 2 35 theme target 518:523 arg1 molecule 525:532 the target molecule 514:532 the target molecule 514:532 During this process, the unique dispersion method increases the contact area between the target molecule and the extraction solvent, and the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule is also enhanced. 37005916 9 36 theme pesticide 1896:1904 arg1 residues 1906:1913 pesticide residues 1896:1913 pesticide residues 1896:1913 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 6 37 from pretreatment 1222:1233 arg1 samples 1266:1272 various samples 1258:1272 various samples 1258:1272 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 0 38 theme effervescence-assisted 55:76 arg1 techniques 94:103 effervescence-assisted microextraction techniques 55:103 effervescence-assisted microextraction techniques 55:103 [Recent advances in the development and application of effervescence-assisted microextraction techniques]. 37005916 3 39 theme low 628:630 arg1 costs 640:644 low running costs 628:644 low running costs 628:644 The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. 37005916 5 40 theme new 907:909 arg1 extractants 911:921 new extractants 907:921 new extractants 907:921 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 5 40 theme new 907:909 arg1 nanomaterials 932:944 nanomaterials 932:944 nanomaterials with multi-pore structures, large specific surface areas, and rich active sites 932:1024 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 0 41 theme techniques 94:103 arg1 application 40:50 application 40:50 application 40:50 [Recent advances in the development and application of effervescence-assisted microextraction techniques]. 37005916 0 41 theme techniques 94:103 arg1 development 24:34 development 24:34 development 24:34 [Recent advances in the development and application of effervescence-assisted microextraction techniques]. 37005916 5 42 theme high 1139:1142 arg1 selectivities 1144:1156 high selectivities 1139:1156 high selectivities 1139:1156 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 14 43 theme sample 3043:3048 arg1 testing 3050:3056 actual sample testing 3036:3056 actual sample testing 3036:3056 In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. 37005916 17 44 dep evaluated 3795:3803 arg1 include 3812:3818 include 3812:3818 evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals 3795:3923 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 14 45 theme similar 3124:3130 arg1 systems 3142:3148 similar detection systems 3124:3148 similar detection systems 3124:3148 In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. 37005916 16 46 from matrices 3754:3761 arg1 terms 3698:3702 terms 3698:3702 terms of the detection of harmful substances in complex matrices 3698:3761 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 11 47 theme solution 2346:2353 arg1 pH 2355:2356 the solution pH 2342:2356 the solution pH 2342:2356 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 5 48 theme liquids 1094:1100 arg1 development 1073:1083 the development 1069:1083 the development of ionic liquids with strong extraction abilities and high selectivities 1069:1156 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 6 49 theme EAM 1176:1178 arg1 result 1164:1169 a result 1162:1169 a result 1162:1169 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 6 49 theme EAM 1176:1178 arg1 technology 1180:1189 the EAM technology 1172:1189 the EAM technology 1172:1189 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 5 50 theme surface 989:995 arg1 areas 997:1001 large specific surface areas 974:1001 large specific surface areas 974:1001 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 13 51 theme enrichment 2882:2891 arg1 EF 2901:2902 EF 2901:2902 EF 2901:2902 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 51 theme enrichment 2882:2891 arg1 factor 2893:2898 the enrichment factor 2878:2898 the enrichment factor (EF) 2878:2903 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 5 52 with nanomaterials 932:944 arg1 sites 1020:1024 rich active sites 1008:1024 rich active sites 1008:1024 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 5 52 with nanomaterials 932:944 arg1 areas 997:1001 large specific surface areas 974:1001 large specific surface areas 974:1001 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 5 52 with nanomaterials 932:944 arg1 structures 962:971 multi-pore structures 951:971 multi-pore structures 951:971 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 2 53 theme target 394:399 arg1 molecule 401:408 the target molecule 390:408 the target molecule 390:408 During this process, the unique dispersion method increases the contact area between the target molecule and the extraction solvent, and the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule is also enhanced. 37005916 5 54 theme strong 1107:1112 arg1 abilities 1125:1133 strong extraction abilities 1107:1133 strong extraction abilities 1107:1133 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 18 55 theme related 3946:3952 arg1 issues 3939:3944 issues 3939:3944 issues related to the application of this technology 3939:3990 Furthermore, issues related to the application of this technology are analyzed, and its future development trend in the field of microextraction is forecasted. 37005916 18 56 theme microextraction 4055:4069 arg1 field 4046:4050 the field 4042:4050 the field of microextraction 4042:4069 Furthermore, issues related to the application of this technology are analyzed, and its future development trend in the field of microextraction is forecasted. 37005916 9 57 theme performance 1741:1751 arg1 chromatography 1760:1773 high performance liquid chromatography 1736:1773 high performance liquid chromatography (HPLC) 1736:1780 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 9 57 theme performance 1741:1751 arg1 HPLC 1776:1779 HPLC 1776:1779 HPLC 1776:1779 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 15 58 theme extraction 3503:3512 arg1 system 3514:3519 the same extraction system 3494:3519 the same extraction system 3494:3519 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 0 59 theme [Recent 0:6 arg1 advances 8:15 [Recent advances 0:15 [Recent advances in the development and application of effervescence-assisted microextraction techniques 0:103 [Recent advances in the development and application of effervescence-assisted microextraction techniques]. 37005916 16 60 theme EAM 3579:3581 arg1 research 3583:3590 EAM research 3579:3590 EAM research 3579:3590 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 14 61 theme method 3004:3009 arg1 use 2992:2994 the use 2988:2994 the use of this method 2988:3009 In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. 37005916 1 62 theme Effervescence-assisted 107:128 arg1 EAM 147:149 EAM 147:149 EAM 147:149 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 1 62 theme Effervescence-assisted 107:128 arg1 microextraction 130:144 Effervescence-assisted microextraction 107:144 Effervescence-assisted microextraction (EAM) 107:150 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 1 62 theme Effervescence-assisted 107:128 arg1 method 183:188 a novel sample pretreatment method 155:188 a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant 155:302 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 16 63 theme detection 3711:3719 arg1 terms 3698:3702 terms 3698:3702 terms of the detection of harmful substances in complex matrices 3698:3761 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 11 64 theme regeneration 2499:2510 arg1 performance 2512:2522 the regeneration performance 2495:2522 the regeneration performance 2495:2522 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 4 65 theme extractants 777:787 arg1 development 762:772 the rapid development 752:772 the rapid development of extractants 752:787 Benefiting from the rapid development of extractants, the evolution and application of the EAM technology is becoming more tuned and diversified. 37005916 2 66 theme extraction 418:427 arg1 solvent 429:435 the extraction solvent 414:435 the extraction solvent 414:435 During this process, the unique dispersion method increases the contact area between the target molecule and the extraction solvent, and the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule is also enhanced. 37005916 13 67 theme correlation 2848:2858 arg1 coefficient 2860:2870 the correlation coefficient 2844:2870 the correlation coefficient (R2) 2844:2875 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 67 theme correlation 2848:2858 arg1 R2 2873:2874 R2 2873:2874 R2 2873:2874 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 5 68 theme large 974:978 arg1 areas 997:1001 large specific surface areas 974:1001 large specific surface areas 974:1001 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 16 69 theme harmful 3724:3730 arg1 substances 3732:3741 harmful substances 3724:3741 harmful substances 3724:3741 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 15 70 dep wherein 3386:3392 arg1 method 3410:3415 the preparation method 3394:3415 the preparation method 3394:3415 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 17 71 theme surface 3854:3860 arg1 water 3862:3866 surface water 3854:3866 surface water 3854:3866 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 17 71 theme surface 3854:3860 arg1 products 3826:3833 dairy products 3820:3833 dairy products 3820:3833 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 19 72 theme EAM 4124:4126 arg1 prospects 4111:4119 the application prospects 4095:4119 the application prospects of EAM in the analysis of various pollutants and components 4095:4179 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 15 73 theme method 3296:3301 arg1 construction 3273:3284 the construction 3269:3284 the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants 3269:3371 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 3 74 theme reduced 647:653 arg1 consumption 663:673 reduced solvent consumption 647:673 reduced solvent consumption 647:673 The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. 37005916 19 75 theme application 4099:4109 arg1 prospects 4111:4119 the application prospects 4095:4119 the application prospects of EAM in the analysis of various pollutants and components 4095:4179 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 2 76 theme dispersion 337:346 arg1 method 348:353 the unique dispersion method 326:353 the unique dispersion method 326:353 During this process, the unique dispersion method increases the contact area between the target molecule and the extraction solvent, and the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule is also enhanced. 37005916 15 77 theme similar 3455:3461 arg1 extractants 3463:3473 similar extractants 3455:3473 similar extractants 3455:3473 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 13 78 theme linear 2830:2835 arg1 range 2837:2841 the linear range 2826:2841 the linear range 2826:2841 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 5 79 theme extensive 1041:1049 arg1 attention 1051:1059 extensive attention 1041:1059 extensive attention 1041:1059 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 13 80 theme quantification 2953:2966 arg1 limit 2910:2914 the limit 2906:2914 the limit of detection (LOD) 2906:2933 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 80 theme quantification 2953:2966 arg1 coefficient 2860:2870 the correlation coefficient 2844:2870 the correlation coefficient (R2) 2844:2875 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 80 theme quantification 2953:2966 arg1 factor 2893:2898 the enrichment factor 2878:2898 the enrichment factor (EF) 2878:2903 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 80 theme quantification 2953:2966 arg1 R2 2873:2874 R2 2873:2874 R2 2873:2874 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 80 theme quantification 2953:2966 arg1 limit 2944:2948 the limit 2940:2948 the limit of quantification (LOQ) 2940:2972 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 80 theme quantification 2953:2966 arg1 EF 2901:2902 EF 2901:2902 EF 2901:2902 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 80 theme quantification 2953:2966 arg1 range 2837:2841 the linear range 2826:2841 the linear range 2826:2841 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 80 theme quantification 2953:2966 arg1 LOD 2930:2932 LOD 2930:2932 LOD 2930:2932 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 80 theme quantification 2953:2966 arg1 LOQ 2969:2971 LOQ 2969:2971 LOQ 2969:2971 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 19 81 theme biological 4269:4278 arg1 samples 4280:4286 food, environmental, and biological samples 4244:4286 food, environmental, and biological samples 4244:4286 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 16 82 from terms 3698:3702 arg1 matrices 3754:3761 complex matrices 3746:3761 complex matrices 3746:3761 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 1 83 theme donors 226:231 arg1 reaction 203:210 the reaction 199:210 the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant 199:302 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 5 84 theme rich 1008:1011 arg1 sites 1020:1024 rich active sites 1008:1024 rich active sites 1008:1024 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 4 85 dep evolution 794:802 arg1 the 790:792 the 790:792 the 790:792 Benefiting from the rapid development of extractants, the evolution and application of the EAM technology is becoming more tuned and diversified. 37005916 14 86 theme method 3246:3251 arg1 superiority 3217:3227 superiority 3217:3227 superiority 3217:3227 In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. 37005916 14 86 theme method 3246:3251 arg1 accuracy 3190:3197 accuracy 3190:3197 accuracy 3190:3197 In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. 37005916 14 86 theme method 3246:3251 arg1 feasibility 3200:3210 feasibility 3200:3210 feasibility 3200:3210 In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. 37005916 3 87 theme high 676:679 arg1 efficiency 692:701 high extraction efficiency 676:701 high extraction efficiency 676:701 The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. 37005916 4 88 theme EAM 827:829 arg1 technology 831:840 the EAM technology 823:840 the EAM technology 823:840 Benefiting from the rapid development of extractants, the evolution and application of the EAM technology is becoming more tuned and diversified. 37005916 2 89 theme contact 369:375 arg1 area 377:380 the contact area 365:380 the contact area between the target molecule and the extraction solvent 365:435 During this process, the unique dispersion method increases the contact area between the target molecule and the extraction solvent, and the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule is also enhanced. 37005916 16 90 from detection 3711:3719 arg1 matrices 3754:3761 complex matrices 3746:3761 complex matrices 3746:3761 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 16 91 theme flame 3638:3642 arg1 AAS 3644:3646 cold flame AAS 3633:3646 cold flame AAS 3633:3646 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 13 92 theme experimental 2792:2803 arg1 limit 2910:2914 the limit 2906:2914 the limit of detection (LOD) 2906:2933 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 92 theme experimental 2792:2803 arg1 coefficient 2860:2870 the correlation coefficient 2844:2870 the correlation coefficient (R2) 2844:2875 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 92 theme experimental 2792:2803 arg1 factor 2893:2898 the enrichment factor 2878:2898 the enrichment factor (EF) 2878:2903 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 92 theme experimental 2792:2803 arg1 limit 2944:2948 the limit 2940:2948 the limit of quantification (LOQ) 2940:2972 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 92 theme experimental 2792:2803 arg1 range 2837:2841 the linear range 2826:2841 the linear range 2826:2841 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 92 theme experimental 2792:2803 arg1 parameters 2805:2814 experimental parameters 2792:2814 experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ) 2792:2972 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 6 93 from compounds 1245:1253 arg1 samples 1266:1272 various samples 1258:1272 various samples 1258:1272 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 7 94 theme interfering 1442:1452 arg1 substrates 1454:1463 other interfering substrates 1436:1463 other interfering substrates 1436:1463 However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. 37005916 10 95 theme pesticides 2149:2158 arg1 concentrations 2069:2082 the concentrations 2065:2082 the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides 2065:2158 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 9 96 theme atomic 1812:1817 arg1 AAS 1844:1846 AAS 1844:1846 AAS 1844:1846 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 9 96 theme atomic 1812:1817 arg1 spectroscopy 1830:1841 atomic absorption spectroscopy 1812:1841 atomic absorption spectroscopy (AAS) 1812:1847 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 3 97 theme EAM 556:558 arg1 technique 560:568 The EAM technique 552:568 The EAM technique 552:568 The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. 37005916 16 98 theme other 3653:3657 arg1 techniques 3670:3679 other analytical techniques 3653:3679 other analytical techniques 3653:3679 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 5 99 theme extractants 911:921 arg1 synthesis 894:902 the synthesis 890:902 the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, 890:1025 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 6 100 theme various 1258:1264 arg1 samples 1266:1272 various samples 1258:1272 various samples 1258:1272 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 2 101 theme adsorption/extraction 446:466 arg1 efficiency 468:477 the adsorption/extraction efficiency 442:477 the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule 442:532 During this process, the unique dispersion method increases the contact area between the target molecule and the extraction solvent, and the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule is also enhanced. 37005916 19 102 from reference 4205:4213 arg1 samples 4280:4286 food, environmental, and biological samples 4244:4286 food, environmental, and biological samples 4244:4286 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 19 103 theme components 4170:4179 arg1 analysis 4135:4142 the analysis 4131:4142 the analysis of various pollutants and components 4131:4179 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 2 104 theme adsorbent/extractant 486:505 arg1 efficiency 468:477 the adsorption/extraction efficiency 442:477 the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule 442:532 During this process, the unique dispersion method increases the contact area between the target molecule and the extraction solvent, and the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule is also enhanced. 37005916 6 105 theme compounds 1245:1253 arg1 pretreatment 1222:1233 the pretreatment 1218:1233 the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples 1218:1332 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 3 106 theme particular 576:585 arg1 interest 587:594 particular interest 576:594 particular interest 576:594 The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. 37005916 14 107 theme detection 3132:3140 arg1 systems 3142:3148 similar detection systems 3124:3148 similar detection systems 3124:3148 In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. 37005916 13 108 theme detection 2919:2927 arg1 limit 2910:2914 the limit 2906:2914 the limit of detection (LOD) 2906:2933 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 108 theme detection 2919:2927 arg1 coefficient 2860:2870 the correlation coefficient 2844:2870 the correlation coefficient (R2) 2844:2875 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 108 theme detection 2919:2927 arg1 factor 2893:2898 the enrichment factor 2878:2898 the enrichment factor (EF) 2878:2903 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 108 theme detection 2919:2927 arg1 R2 2873:2874 R2 2873:2874 R2 2873:2874 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 108 theme detection 2919:2927 arg1 limit 2944:2948 the limit 2940:2948 the limit of quantification (LOQ) 2940:2972 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 108 theme detection 2919:2927 arg1 EF 2901:2902 EF 2901:2902 EF 2901:2902 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 108 theme detection 2919:2927 arg1 range 2837:2841 the linear range 2826:2841 the linear range 2826:2841 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 108 theme detection 2919:2927 arg1 LOD 2930:2932 LOD 2930:2932 LOD 2930:2932 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 13 108 theme detection 2919:2927 arg1 LOQ 2969:2971 LOQ 2969:2971 LOQ 2969:2971 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 19 109 theme pollutants 4155:4164 arg1 analysis 4135:4142 the analysis 4131:4142 the analysis of various pollutants and components 4131:4179 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 6 110 theme environmental 1312:1324 arg1 samples 1326:1332 food, plant, biological, and environmental samples 1283:1332 food, plant, biological, and environmental samples 1283:1332 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 0 111 dep development 24:34 arg1 the 20:22 the 20:22 the 20:22 [Recent advances in the development and application of effervescence-assisted microextraction techniques]. 37005916 10 112 theme bisphenol 2111:2119 arg1 concentrations 2069:2082 the concentrations 2065:2082 the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides 2065:2158 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 9 113 theme treated 1652:1658 arg1 samples 1660:1666 The treated samples 1648:1666 The treated samples 1648:1666 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 11 114 theme extractant 2415:2424 arg1 type 2431:2434 the type 2427:2434 the type of eluent 2427:2444 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 114 theme extractant 2415:2424 arg1 mass/volume 2400:2410 mass/volume 2400:2410 mass/volume 2400:2410 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 114 theme extractant 2415:2424 arg1 temperature 2374:2384 the extraction temperature 2359:2384 the extraction temperature 2359:2384 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 114 theme extractant 2415:2424 arg1 performance 2512:2522 the regeneration performance 2495:2522 the regeneration performance 2495:2522 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 114 theme extractant 2415:2424 arg1 time 2485:2488 the elution time 2473:2488 the elution time 2473:2488 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 114 theme extractant 2415:2424 arg1 pH 2355:2356 the solution pH 2342:2356 the solution pH 2342:2356 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 114 theme extractant 2415:2424 arg1 composition 2302:2312 the composition 2298:2312 the composition of the effervescent tablet 2298:2339 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 114 theme extractant 2415:2424 arg1 concentration 2458:2470 the eluent concentration 2447:2470 the eluent concentration 2447:2470 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 114 theme extractant 2415:2424 arg1 type 2391:2394 the type 2387:2394 the type 2387:2394 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 19 115 theme food 4244:4247 arg1 samples 4280:4286 food, environmental, and biological samples 4244:4286 food, environmental, and biological samples 4244:4286 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 3 116 theme convenient 604:613 arg1 application 615:625 its convenient application 600:625 its convenient application 600:625 The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. 37005916 15 117 theme emerging 3352:3359 arg1 extractants 3361:3371 other emerging extractants 3346:3371 other emerging extractants 3346:3371 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 12 118 theme multi-factor 2582:2593 arg1 optimization 2595:2606 multi-factor optimization 2582:2606 multi-factor optimization 2582:2606 Generally, the cumbersome single factor optimization and multi-factor optimization methods are also required to determine the optimal experimental conditions. 37005916 10 119 theme Pb2+ 2087:2090 arg1 concentrations 2069:2082 the concentrations 2065:2082 the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides 2065:2158 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 5 120 theme ionic 1088:1092 arg1 liquids 1094:1100 ionic liquids 1088:1100 ionic liquids with strong extraction abilities and high selectivities 1088:1156 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 18 121 theme technology 3981:3990 arg1 application 3961:3971 the application 3957:3971 the application of this technology 3957:3990 Furthermore, issues related to the application of this technology are analyzed, and its future development trend in the field of microextraction is forecasted. 37005916 9 122 theme metal 1884:1888 arg1 ions 1890:1893 heavy metal ions 1878:1893 heavy metal ions 1878:1893 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 3 123 theme running 632:638 arg1 costs 640:644 low running costs 628:644 low running costs 628:644 The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. 37005916 14 124 theme obtained 3067:3074 arg1 results 3076:3082 the obtained results 3063:3082 the obtained results 3063:3082 In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. 37005916 16 125 theme substances 3732:3741 arg1 detection 3711:3719 the detection 3707:3719 the detection of harmful substances in complex matrices 3707:3761 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 12 126 theme single 2551:2556 arg1 optimization 2565:2576 cumbersome single factor optimization 2540:2576 cumbersome single factor optimization 2540:2576 Generally, the cumbersome single factor optimization and multi-factor optimization methods are also required to determine the optimal experimental conditions. 37005916 10 127 theme Ni2+ 2099:2102 arg1 concentrations 2069:2082 the concentrations 2065:2082 the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides 2065:2158 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 5 128 with liquids 1094:1100 arg1 abilities 1125:1133 strong extraction abilities 1107:1133 strong extraction abilities 1107:1133 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 5 128 with liquids 1094:1100 arg1 selectivities 1144:1156 high selectivities 1139:1156 high selectivities 1139:1156 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 0 129 theme microextraction 78:92 arg1 techniques 94:103 effervescence-assisted microextraction techniques 55:103 effervescence-assisted microextraction techniques 55:103 [Recent advances in the development and application of effervescence-assisted microextraction techniques]. 37005916 13 130 theme conditions 2736:2745 arg1 determination 2694:2706 determination 2694:2706 determination of the optimal experimental conditions 2694:2745 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 1 131 theme novel 157:161 arg1 microextraction 130:144 Effervescence-assisted microextraction 107:144 Effervescence-assisted microextraction (EAM) 107:150 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 1 131 theme novel 157:161 arg1 method 183:188 a novel sample pretreatment method 155:188 a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant 155:302 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 16 132 theme complex 3746:3752 arg1 matrices 3754:3761 complex matrices 3746:3761 complex matrices 3746:3761 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 9 133 theme EAM 1700:1702 arg1 method 1704:1709 the EAM method 1696:1709 the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics 1696:1969 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 11 134 theme extraction 2363:2372 arg1 temperature 2374:2384 the extraction temperature 2359:2384 the extraction temperature 2359:2384 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 10 135 theme Cd2+ 2093:2096 arg1 concentrations 2069:2082 the concentrations 2065:2082 the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides 2065:2158 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 19 136 theme environmental 4250:4262 arg1 samples 4280:4286 food, environmental, and biological samples 4244:4286 food, environmental, and biological samples 4244:4286 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 16 137 theme current 3539:3545 arg1 state-of-the-art 3547:3562 the current state-of-the-art 3535:3562 the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques 3535:3679 In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. 37005916 1 138 theme pretreatment 170:181 arg1 microextraction 130:144 Effervescence-assisted microextraction 107:144 Effervescence-assisted microextraction (EAM) 107:150 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 1 138 theme pretreatment 170:181 arg1 method 183:188 a novel sample pretreatment method 155:188 a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant 155:302 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 11 139 theme influencing 2221:2231 arg1 factors 2233:2239 many influencing factors 2216:2239 many influencing factors 2216:2239 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 9 140 theme prior 1711:1715 arg1 method 1704:1709 the EAM method 1696:1709 the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics 1696:1969 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 0 141 from advances 8:15 arg1 application 40:50 application 40:50 application 40:50 [Recent advances in the development and application of effervescence-assisted microextraction techniques]. 37005916 0 141 from advances 8:15 arg1 development 24:34 development 24:34 development 24:34 [Recent advances in the development and application of effervescence-assisted microextraction techniques]. 37005916 9 142 theme endocrine-disrupting 1916:1935 arg1 EDCs 1948:1951 EDCs 1948:1951 EDCs 1948:1951 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 9 142 theme endocrine-disrupting 1916:1935 arg1 compounds 1937:1945 endocrine-disrupting compounds 1916:1945 endocrine-disrupting compounds (EDCs) 1916:1952 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 15 143 theme application 3418:3428 arg1 range 3430:3434 application range 3418:3434 application range 3418:3434 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 13 144 theme experimental 2723:2734 arg1 conditions 2736:2745 the optimal experimental conditions 2711:2745 the optimal experimental conditions 2711:2745 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 14 145 theme actual 3036:3041 arg1 testing 3050:3056 actual sample testing 3036:3056 actual sample testing 3036:3056 In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. 37005916 5 146 theme specific 980:987 arg1 areas 997:1001 large specific surface areas 974:1001 large specific surface areas 974:1001 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 10 147 theme Cu2+ 2105:2108 arg1 concentrations 2069:2082 the concentrations 2065:2082 the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides 2065:2158 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 15 148 theme preparation 3398:3408 arg1 method 3410:3415 the preparation method 3394:3415 the preparation method 3394:3415 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 13 149 theme optimal 2715:2721 arg1 conditions 2736:2745 the optimal experimental conditions 2711:2745 the optimal experimental conditions 2711:2745 Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). 37005916 9 150 theme high 1736:1739 arg1 chromatography 1760:1773 high performance liquid chromatography 1736:1773 high performance liquid chromatography (HPLC) 1736:1780 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 9 150 theme high 1736:1739 arg1 HPLC 1776:1779 HPLC 1776:1779 HPLC 1776:1779 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 5 151 theme extraction 1114:1123 arg1 abilities 1125:1133 strong extraction abilities 1107:1133 strong extraction abilities 1107:1133 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 18 152 theme development 4021:4031 arg1 trend 4033:4037 its future development trend 4010:4037 its future development trend in the field of microextraction 4010:4069 Furthermore, issues related to the application of this technology are analyzed, and its future development trend in the field of microextraction is forecasted. 37005916 5 153 theme multi-pore 951:960 arg1 structures 962:971 multi-pore structures 951:971 multi-pore structures 951:971 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 9 154 theme liquid 1753:1758 arg1 chromatography 1760:1773 high performance liquid chromatography 1736:1773 high performance liquid chromatography (HPLC) 1736:1780 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 9 154 theme liquid 1753:1758 arg1 HPLC 1776:1779 HPLC 1776:1779 HPLC 1776:1779 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 10 155 theme estrogen 2122:2129 arg1 concentrations 2069:2082 the concentrations 2065:2082 the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides 2065:2158 Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. 37005916 4 156 theme rapid 756:760 arg1 development 762:772 the rapid development 752:772 the rapid development of extractants 752:787 Benefiting from the rapid development of extractants, the evolution and application of the EAM technology is becoming more tuned and diversified. 37005916 7 157 contain contain 1370:1376 arg2 substrates 1454:1463 other interfering substrates 1436:1463 other interfering substrates 1436:1463 However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. 37005916 7 157 contain contain 1370:1376 arg1 samples 1356:1362 these samples 1350:1362 these samples 1350:1362 However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. 37005916 7 157 contain contain 1370:1376 arg2 polysaccharides 1378:1392 polysaccharides 1378:1392 polysaccharides 1378:1392 However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. 37005916 7 157 contain contain 1370:1376 arg2 peptides 1395:1402 peptides 1395:1402 peptides 1395:1402 However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. 37005916 7 157 contain contain 1370:1376 arg2 salts 1425:1429 inorganic salts 1415:1429 inorganic salts 1415:1429 However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. 37005916 7 157 contain contain 1370:1376 arg2 proteins 1405:1412 proteins 1405:1412 proteins 1405:1412 However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. 37005916 19 158 from prospects 4111:4119 arg1 analysis 4135:4142 the analysis 4131:4142 the analysis of various pollutants and components 4131:4179 Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples. 37005916 3 159 theme solvent 655:661 arg1 consumption 663:673 reduced solvent consumption 647:673 reduced solvent consumption 647:673 The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. 37005916 15 160 theme same 3498:3501 arg1 system 3514:3519 the same extraction system 3494:3519 the same extraction system 3494:3519 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 1 161 theme extractant 293:302 arg1 dispersion 275:284 rapid dispersion 269:284 rapid dispersion of the extractant 269:302 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 15 162 theme extractants 3463:3473 arg1 wherein 3386:3392 wherein the preparation method, application range, and comparison of similar extractants 3386:3473 wherein 3386:3392 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 15 162 theme extractants 3463:3473 arg1 range 3430:3434 application range 3418:3434 application range 3418:3434 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 15 162 theme extractants 3463:3473 arg1 comparison 3441:3450 comparison 3441:3450 comparison of similar extractants 3441:3473 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 7 163 theme inorganic 1415:1423 arg1 salts 1425:1429 inorganic salts 1415:1429 inorganic salts 1415:1429 However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. 37005916 12 164 theme experimental 2659:2670 arg1 conditions 2672:2681 the optimal experimental conditions 2647:2681 the optimal experimental conditions 2647:2681 Generally, the cumbersome single factor optimization and multi-factor optimization methods are also required to determine the optimal experimental conditions. 37005916 4 165 theme technology 831:840 arg1 application 808:818 application 808:818 application 808:818 Benefiting from the rapid development of extractants, the evolution and application of the EAM technology is becoming more tuned and diversified. 37005916 4 165 theme technology 831:840 arg1 evolution 794:802 evolution 794:802 evolution 794:802 Benefiting from the rapid development of extractants, the evolution and application of the EAM technology is becoming more tuned and diversified. 37005916 18 166 theme future 4014:4019 arg1 development 4021:4031 its future development 4010:4031 its future development trend in the field of microextraction 4010:4069 Furthermore, issues related to the application of this technology are analyzed, and its future development trend in the field of microextraction is forecasted. 37005916 9 167 theme gas 1783:1785 arg1 GC 1803:1804 GC 1803:1804 GC 1803:1804 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 9 167 theme gas 1783:1785 arg1 chromatography 1787:1800 gas chromatography 1783:1800 gas chromatography (GC) 1783:1805 The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. 37005916 3 168 theme extraction 681:690 arg1 efficiency 692:701 high extraction efficiency 676:701 high extraction efficiency 676:701 The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. 37005916 1 169 theme sample 163:168 arg1 microextraction 130:144 Effervescence-assisted microextraction 107:144 Effervescence-assisted microextraction (EAM) 107:150 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 1 169 theme sample 163:168 arg1 method 183:188 a novel sample pretreatment method 155:188 a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant 155:302 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 37005916 2 170 theme unique 330:335 arg1 method 348:353 the unique dispersion method 326:353 the unique dispersion method 326:353 During this process, the unique dispersion method increases the contact area between the target molecule and the extraction solvent, and the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule is also enhanced. 37005916 17 171 theme complex 3906:3912 arg1 products 3826:3833 dairy products 3820:3833 dairy products 3820:3833 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 17 171 theme complex 3906:3912 arg1 botanicals 3914:3923 complex botanicals 3906:3923 complex botanicals 3906:3923 More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. 37005916 11 172 theme many 2216:2219 arg1 factors 2233:2239 many influencing factors 2216:2239 many influencing factors 2216:2239 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 173 theme eluent 2451:2456 arg1 concentration 2458:2470 the eluent concentration 2447:2470 the eluent concentration 2447:2470 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 11 174 theme effervescent 2321:2332 arg1 tablet 2334:2339 the effervescent tablet 2317:2339 the effervescent tablet 2317:2339 Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. 37005916 6 175 from samples 1266:1272 arg1 pretreatment 1222:1233 the pretreatment 1218:1233 the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples 1218:1332 As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. 37005916 15 176 theme ionic 3327:3331 arg1 liquids 3333:3339 ionic liquids 3327:3339 ionic liquids 3327:3339 In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. 37005916 5 177 theme active 1013:1018 arg1 sites 1020:1024 rich active sites 1008:1024 rich active sites 1008:1024 Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. 37005916 14 178 theme developed 3236:3244 arg1 method 3246:3251 the developed method 3232:3251 the developed method 3232:3251 In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. 37005916 3 179 theme environmental 708:720 arg1 friendliness 722:733 environmental friendliness 708:733 environmental friendliness 708:733 The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. 37005916 1 180 theme CO2 245:247 arg1 bubbles 249:255 CO2 bubbles 245:255 CO2 bubbles 245:255 Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. 36637127 15 0 theme fiber-rich 2508:2517 arg1 diets 2519:2523 all four fiber-rich diets 2499:2523 all four fiber-rich diets 2499:2523 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 2 1 theme study 322:326 arg1 purpose 306:312 The purpose 302:312 The purpose of this study 302:326 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 5 2 theme protein 971:977 arg1 pools 954:958 body pools 949:958 body pools of fat and protein 949:977 Body weight and backfat were measured, and body pools of fat and protein were estimated using the deuterium oxide dilution technique at day 0, 30 and 60. 36637127 7 3 theme heat 1182:1185 arg1 production 1187:1196 total heat production 1176:1196 total heat production 1176:1196 On day 15 and 45, heart rate was measured to estimate total heat production. 36637127 7 4 theme heart 1140:1144 arg1 rate 1146:1149 heart rate 1140:1149 heart rate 1140:1149 On day 15 and 45, heart rate was measured to estimate total heat production. 36637127 12 5 theme gross 1853:1857 arg1 intake 1866:1871 gross energy intake 1853:1871 gross energy intake 1853:1871 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 13 6 theme total 2031:2035 arg1 retention 2044:2052 the total energy retention 2027:2052 the total energy retention 2027:2052 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 8 7 theme organic 1377:1383 arg1 matter 1385:1390 organic matter 1377:1390 organic matter 1377:1390 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 1 8 theme most 256:259 arg1 data 261:264 most data 256:264 most data 256:264 The digestibility of energy and nutrients in fiber-rich diets depends greatly on the fiber source but most data are from studies with growing pigs. 36637127 14 9 theme most 2186:2189 arg1 N 2191:2191 most N 2186:2191 most N 2186:2191 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 9 10 theme P 1533:1533 arg1 < 1535:1535 P < 0.001 1533:1541 P < 0.001 1533:1541 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 13 11 theme PKE 2092:2094 arg1 sows 2100:2103 PKE fed sows 2092:2103 PKE fed sows 2092:2103 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 15 12 theme ATTD 2474:2477 arg1 values 2479:2484 ATTD values 2474:2484 ATTD values above 82% in all four fiber-rich diets 2474:2523 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 1 13 with studies 275:281 arg1 pigs 296:299 growing pigs 288:299 growing pigs 288:299 The digestibility of energy and nutrients in fiber-rich diets depends greatly on the fiber source but most data are from studies with growing pigs. 36637127 12 14 from energy 1887:1892 arg1 urine 1913:1917 urine 1913:1917 urine (3-4%) 1913:1924 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 12 14 from energy 1887:1892 arg1 methane 1930:1936 methane 1930:1936 methane (0.5-0.9%) 1930:1947 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 12 14 from energy 1887:1892 arg1 feces 1897:1901 feces 1897:1901 feces (15-17%) 1897:1910 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 12 14 from energy 1887:1892 arg1 % 1946:1946 0.5-0.9% 1939:1946 0.5-0.9% 1939:1946 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 12 14 from energy 1887:1892 arg1 % 1909:1909 15-17% 1904:1909 15-17% 1904:1909 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 12 14 from energy 1887:1892 arg1 % 1923:1923 3-4% 1920:1923 3-4% 1920:1923 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 3 15 theme mixed 639:643 arg1 MF 652:653 MF 652:653 MF 652:653 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 3 15 theme mixed 639:643 arg1 fiber 645:649 a mixed fiber 637:649 a mixed fiber (MF) 637:654 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 4 16 theme diets 878:882 arg1 diets 878:882 the four diets 869:882 the four diets 869:882 A total of 48 multiparous sows were stratified by body weight at mating (day 0) and assigned to one of the four diets throughout gestation. 36637127 4 16 theme diets 878:882 arg1 one 862:864 one 862:864 one 862:864 A total of 48 multiparous sows were stratified by body weight at mating (day 0) and assigned to one of the four diets throughout gestation. 36637127 0 17 theme nitrogen 112:119 arg1 digestibility 44:56 digestibility 44:56 digestibility of energy and nutrients 44:80 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 0 17 theme nitrogen 112:119 arg1 utilization 86:96 utilization 86:96 utilization of energy and nitrogen 86:119 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 11 18 theme MF 1799:1800 arg1 sows 1806:1809 the MF fed sows 1795:1809 the MF fed sows 1795:1809 The ATTP of N was highest in the MF fed sows and ATTD of NSP was lowest in the MF fed sows. 36637127 0 19 theme early 124:128 arg1 sows 148:151 early and mid-gestating sows 124:151 early and mid-gestating sows 124:151 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 2 20 from metabolism 463:472 arg1 sows 530:533 gestating sows 520:533 gestating sows 520:533 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 9 21 theme non-starch 1569:1578 arg1 polysaccharides 1580:1594 insoluble non-starch polysaccharides 1559:1594 insoluble non-starch polysaccharides (NSP) 1559:1600 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 9 21 theme non-starch 1569:1578 arg1 NSP 1597:1599 NSP 1597:1599 NSP 1597:1599 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 0 22 theme mid-gestating 134:146 arg1 sows 148:151 early and mid-gestating sows 124:151 early and mid-gestating sows 124:151 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 3 23 theme fiber-rich 541:550 arg1 diets 552:556 Four fiber-rich diets 536:556 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) 536:654 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 2 24 theme gestating 520:528 arg1 sows 530:533 gestating sows 520:533 gestating sows 520:533 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 2 25 from utilization 478:488 arg1 sows 530:533 gestating sows 520:533 gestating sows 520:533 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 8 26 dep in 1344:1345 arg1 vitro 1347:1351 vitro 1347:1351 vitro 1347:1351 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 10 27 theme nutrients 1619:1627 arg1 ATTD 1607:1610 The ATTD 1603:1610 The ATTD of all nutrients except NSP 1603:1638 The ATTD of all nutrients except NSP was lowest in PKE fed sows and highest, except for N, in sows fed the SBP diet. 36637127 10 27 theme nutrients 1619:1627 arg1 lowest 1644:1649 lowest 1644:1649 lowest 1644:1649 The ATTD of all nutrients except NSP was lowest in PKE fed sows and highest, except for N, in sows fed the SBP diet. 36637127 3 28 theme total 705:709 arg1 TF 718:719 TF 718:719 TF 718:719 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 3 28 theme total 705:709 arg1 fiber 711:715 total fiber 705:715 total fiber (TF) of 471 705:727 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 4 29 theme sows 792:795 arg1 total 768:772 A total 766:772 A total of 48 multiparous sows 766:795 A total of 48 multiparous sows were stratified by body weight at mating (day 0) and assigned to one of the four diets throughout gestation. 36637127 0 30 from utilization 86:96 arg1 sows 148:151 early and mid-gestating sows 124:151 early and mid-gestating sows 124:151 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 13 31 theme retention 2044:2052 arg1 majority 1991:1998 the majority 1987:1998 the majority of the heat production and the total energy retention 1987:2052 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 0 32 theme energy 61:66 arg1 digestibility 44:56 digestibility 44:56 digestibility of energy and nutrients 44:80 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 0 32 theme energy 61:66 arg1 utilization 86:96 utilization 86:96 utilization of energy and nitrogen 86:119 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 5 33 theme Body 906:909 arg1 weight 911:916 Body weight 906:916 Body weight 906:916 Body weight and backfat were measured, and body pools of fat and protein were estimated using the deuterium oxide dilution technique at day 0, 30 and 60. 36637127 3 34 theme sugar 567:571 arg1 SBP 584:586 SBP 584:586 SBP 584:586 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 3 34 theme sugar 567:571 arg1 pulp 578:581 sugar beet pulp 567:581 sugar beet pulp (SBP) 567:587 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 1 35 from digestibility 158:170 arg1 diets 210:214 fiber-rich diets 199:214 fiber-rich diets 199:214 The digestibility of energy and nutrients in fiber-rich diets depends greatly on the fiber source but most data are from studies with growing pigs. 36637127 3 36 theme 471 725:727 arg1 TF 718:719 TF 718:719 TF 718:719 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 3 36 theme 471 725:727 arg1 fiber 711:715 total fiber 705:715 total fiber (TF) of 471 705:727 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 3 36 theme 471 725:727 arg1 437 g/d 743:749 437 g/d 743:749 437 g/d 743:749 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 2 37 theme whole-body 452:461 arg1 metabolism 463:472 whole-body metabolism 452:472 whole-body metabolism 452:472 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 0 38 theme nutrients 72:80 arg1 digestibility 44:56 digestibility 44:56 digestibility of energy and nutrients 44:80 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 0 38 theme nutrients 72:80 arg1 utilization 86:96 utilization 86:96 utilization of energy and nitrogen 86:119 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 8 39 dep up 1318:1319 arg1 to 1321:1322 to 1321:1322 to 1321:1322 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 0 40 from Influence 0:8 arg1 digestibility 44:56 digestibility 44:56 digestibility of energy and nutrients 44:80 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 0 40 from Influence 0:8 arg1 utilization 86:96 utilization 86:96 utilization of energy and nitrogen 86:119 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 3 41 theme average 681:687 arg1 intake 695:700 an average daily intake 678:700 an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d 678:749 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 6 42 theme fecal 1088:1092 arg1 grab 1094:1097 fecal grab 1088:1097 fecal grab 1088:1097 On day 30 and 60, urine and fecal grab samples were obtained. 36637127 13 43 theme P 2164:2164 arg1 < 2166:2166 P < 0.001 2164:2172 P < 0.001 2164:2172 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 3 44 theme 651 735:737 arg1 intake 695:700 an average daily intake 678:700 an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d 678:749 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 0 45 from digestibility 44:56 arg1 sows 148:151 early and mid-gestating sows 124:151 early and mid-gestating sows 124:151 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 2 46 theme tract 366:370 arg1 ATTD 387:390 ATTD 387:390 ATTD 387:390 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 2 46 theme tract 366:370 arg1 digestibility 372:384 the apparent total tract digestibility 347:384 the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets 347:434 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 0 47 theme energy 101:106 arg1 digestibility 44:56 digestibility 44:56 digestibility of energy and nutrients 44:80 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 0 47 theme energy 101:106 arg1 utilization 86:96 utilization 86:96 utilization of energy and nitrogen 86:119 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 3 48 theme 507 730:732 arg1 intake 695:700 an average daily intake 678:700 an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d 678:749 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 2 49 theme different 409:417 arg1 diets 430:434 different fiber-rich diets 409:434 different fiber-rich diets 409:434 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 11 50 theme MF 1753:1754 arg1 sows 1760:1763 the MF fed sows 1749:1763 the MF fed sows 1749:1763 The ATTP of N was highest in the MF fed sows and ATTD of NSP was lowest in the MF fed sows. 36637127 2 51 theme apparent 351:358 arg1 ATTD 387:390 ATTD 387:390 ATTD 387:390 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 2 51 theme apparent 351:358 arg1 digestibility 372:384 the apparent total tract digestibility 347:384 the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets 347:434 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 14 52 theme 50-63 2296:2300 arg1 % 2301:2301 50-63% 2296:2301 50-63% 2296:2301 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 5 53 theme body 949:952 arg1 pools 954:958 body pools 949:958 body pools of fat and protein 949:977 Body weight and backfat were measured, and body pools of fat and protein were estimated using the deuterium oxide dilution technique at day 0, 30 and 60. 36637127 13 54 theme MJ/d 2144:2147 arg1 retention 2113:2121 a retention 2111:2121 a retention of 3.3 MJ/d and 13.3 MJ/d 2111:2147 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 2 55 theme nutrients 396:404 arg1 ATTD 387:390 ATTD 387:390 ATTD 387:390 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 2 55 theme nutrients 396:404 arg1 digestibility 372:384 the apparent total tract digestibility 347:384 the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets 347:434 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 13 56 theme heat 2007:2010 arg1 production 2012:2021 the heat production 2003:2021 the heat production 2003:2021 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 3 57 theme 437 g/d 743:749 arg1 intake 695:700 an average daily intake 678:700 an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d 678:749 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 4 58 theme body 816:819 arg1 weight 821:826 body weight 816:826 body weight 816:826 A total of 48 multiparous sows were stratified by body weight at mating (day 0) and assigned to one of the four diets throughout gestation. 36637127 12 59 theme 3-4 1920:1922 arg1 urine 1913:1917 urine 1913:1917 urine (3-4%) 1913:1924 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 12 59 theme 3-4 1920:1922 arg1 % 1923:1923 3-4% 1920:1923 3-4% 1920:1923 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 0 60 theme supplements 29:39 arg1 Influence 0:8 Influence 0:8 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 0:152 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 14 61 theme SBP 2282:2284 arg1 sows 2290:2293 SBP fed sows 2282:2293 SBP fed sows (50-63%, respectively) 2282:2316 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 15 62 theme high 2538:2541 arg1 content 2546:2552 the high TF content 2534:2552 the high TF content in the diets 2534:2565 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 14 63 dep % 2327:2327 arg1 to 2329:2330 to 2329:2330 to 2329:2330 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 11 64 theme fed 1756:1758 arg1 sows 1760:1763 the MF fed sows 1749:1763 the MF fed sows 1749:1763 The ATTP of N was highest in the MF fed sows and ATTD of NSP was lowest in the MF fed sows. 36637127 15 65 theme gestating 2431:2439 arg1 sows 2441:2444 gestating sows 2431:2444 gestating sows with respect to energy 2431:2467 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 8 66 theme in 1267:1268 arg1 digestibility 1290:1302 in vivo organic matter digestibility 1267:1302 in vivo organic matter digestibility 1267:1302 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 10 67 theme PKE 1654:1656 arg1 sows 1662:1665 PKE fed sows 1654:1665 PKE fed sows 1654:1665 The ATTD of all nutrients except NSP was lowest in PKE fed sows and highest, except for N, in sows fed the SBP diet. 36637127 8 68 theme organic 1275:1281 arg1 digestibility 1290:1302 in vivo organic matter digestibility 1267:1302 in vivo organic matter digestibility 1267:1302 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 13 69 theme MJ/d 2130:2133 arg1 retention 2113:2121 a retention 2111:2121 a retention of 3.3 MJ/d and 13.3 MJ/d 2111:2147 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 5 70 theme deuterium 1004:1012 arg1 technique 1029:1037 the deuterium oxide dilution technique 1000:1037 the deuterium oxide dilution technique 1000:1037 Body weight and backfat were measured, and body pools of fat and protein were estimated using the deuterium oxide dilution technique at day 0, 30 and 60. 36637127 3 71 theme kernel 611:616 arg1 PKE 629:631 PKE 629:631 PKE 629:631 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 3 71 theme kernel 611:616 arg1 expellers 618:626 palm kernel expellers 606:626 palm kernel expellers (PKE) 606:632 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 8 72 theme in 1344:1345 arg1 digestibility 1360:1372 in vitro enzyme digestibility 1344:1372 in vitro enzyme digestibility of organic matter 1344:1390 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 1 73 theme fiber 239:243 arg1 source 245:250 the fiber source 235:250 the fiber source 235:250 The digestibility of energy and nutrients in fiber-rich diets depends greatly on the fiber source but most data are from studies with growing pigs. 36637127 7 74 theme total 1176:1180 arg1 production 1187:1196 total heat production 1176:1196 total heat production 1176:1196 On day 15 and 45, heart rate was measured to estimate total heat production. 36637127 15 75 theme N 2583:2583 arg1 utilization 2585:2595 the N utilization 2579:2595 the N utilization in gestating sows 2579:2613 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 15 76 from utilization 2585:2595 arg1 sows 2610:2613 gestating sows 2600:2613 gestating sows 2600:2613 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 12 77 dep heat 1837:1840 arg1 intake 1866:1871 gross energy intake 1853:1871 gross energy intake 1853:1871 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 12 77 dep heat 1837:1840 arg1 % 1848:1848 53-72% 1843:1848 53-72% of gross energy intake 1843:1871 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 8 78 theme enzyme 1353:1358 arg1 digestibility 1360:1372 in vitro enzyme digestibility 1344:1372 in vitro enzyme digestibility of organic matter 1344:1390 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 13 79 theme fed 2096:2098 arg1 sows 2100:2103 PKE fed sows 2092:2103 PKE fed sows 2092:2103 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 11 80 theme N 1732:1732 arg1 ATTP 1724:1727 The ATTP 1720:1727 The ATTP of N 1720:1732 The ATTP of N was highest in the MF fed sows and ATTD of NSP was lowest in the MF fed sows. 36637127 11 80 theme N 1732:1732 arg1 highest 1738:1744 highest 1738:1744 highest 1738:1744 The ATTP of N was highest in the MF fed sows and ATTD of NSP was lowest in the MF fed sows. 36637127 14 81 located observed 2263:2270 arg2 loss 2233:2236 the lowest and highest N loss 2208:2236 loss 2233:2236 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 14 81 located observed 2263:2270 arg1 SH 2275:2276 SH 2275:2276 SH 2275:2276 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 14 81 located observed 2263:2270 arg2 lowest 2212:2217 lowest 2212:2217 lowest 2212:2217 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 14 81 located observed 2263:2270 arg1 sows 2290:2293 SBP fed sows 2282:2293 SBP fed sows (50-63%, respectively) 2282:2316 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 11 82 theme NSP 1777:1779 arg1 ATTD 1769:1772 ATTD 1769:1772 ATTD of NSP 1769:1779 The ATTP of N was highest in the MF fed sows and ATTD of NSP was lowest in the MF fed sows. 36637127 8 83 theme matter 1385:1390 arg1 digestibility 1360:1372 in vitro enzyme digestibility 1344:1372 in vitro enzyme digestibility of organic matter 1344:1390 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 1 84 theme energy 175:180 arg1 digestibility 158:170 The digestibility 154:170 The digestibility of energy and nutrients in fiber-rich diets 154:214 The digestibility of energy and nutrients in fiber-rich diets depends greatly on the fiber source but most data are from studies with growing pigs. 36637127 15 85 used utilized 2407:2414 arg2 diets 2396:2400 the fiber-rich diets 2381:2400 the fiber-rich diets 2381:2400 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 10 86 theme SBP 1710:1712 arg1 diet 1714:1717 the SBP diet 1706:1717 the SBP diet 1706:1717 The ATTD of all nutrients except NSP was lowest in PKE fed sows and highest, except for N, in sows fed the SBP diet. 36637127 1 87 theme nutrients 186:194 arg1 digestibility 158:170 The digestibility 154:170 The digestibility of energy and nutrients in fiber-rich diets 154:214 The digestibility of energy and nutrients in fiber-rich diets depends greatly on the fiber source but most data are from studies with growing pigs. 36637127 11 88 theme fed 1802:1804 arg1 sows 1806:1809 the MF fed sows 1795:1809 the MF fed sows 1795:1809 The ATTP of N was highest in the MF fed sows and ATTD of NSP was lowest in the MF fed sows. 36637127 14 89 theme highest 2223:2229 arg1 loss 2233:2236 the lowest and highest N loss 2208:2236 loss 2233:2236 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 8 90 dep in 1267:1268 arg1 vivo 1270:1273 vivo 1270:1273 vivo 1270:1273 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 14 91 theme 26 2332:2333 arg1 % 2327:2327 % 2327:2327 % 2327:2327 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 1 92 theme fiber-rich 199:208 arg1 diets 210:214 fiber-rich diets 199:214 fiber-rich diets 199:214 The digestibility of energy and nutrients in fiber-rich diets depends greatly on the fiber source but most data are from studies with growing pigs. 36637127 14 93 dep sows 2290:2293 arg1 % 2301:2301 50-63% 2296:2301 50-63% 2296:2301 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 2 94 theme nitrogen 504:511 arg1 metabolism 463:472 whole-body metabolism 452:472 whole-body metabolism 452:472 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 2 94 theme nitrogen 504:511 arg1 utilization 478:488 utilization 478:488 utilization 478:488 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 9 95 theme insoluble 1559:1567 arg1 polysaccharides 1580:1594 insoluble non-starch polysaccharides 1559:1594 insoluble non-starch polysaccharides (NSP) 1559:1600 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 9 95 theme insoluble 1559:1567 arg1 NSP 1597:1599 NSP 1597:1599 NSP 1597:1599 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 13 96 theme production 2012:2021 arg1 majority 1991:1998 the majority 1987:1998 the majority of the heat production and the total energy retention 1987:2052 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 9 97 theme polysaccharides 1580:1594 arg1 intake 1549:1554 intake 1549:1554 intake of insoluble non-starch polysaccharides (NSP) 1549:1600 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 3 98 theme beet 573:576 arg1 SBP 584:586 SBP 584:586 SBP 584:586 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 3 98 theme beet 573:576 arg1 pulp 578:581 sugar beet pulp 567:581 sugar beet pulp (SBP) 567:587 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 9 99 theme energy 1405:1410 arg1 ATTD 1397:1400 The ATTD 1393:1400 The ATTD of energy 1393:1410 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 12 100 theme most 1822:1825 arg1 energy 1827:1832 most energy 1822:1832 most energy 1822:1832 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 13 101 theme energy 2037:2042 arg1 retention 2044:2052 the total energy retention 2027:2052 the total energy retention 2027:2052 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 15 102 theme gestating 2600:2608 arg1 sows 2610:2613 gestating sows 2600:2613 gestating sows 2600:2613 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 3 103 theme fiber 711:715 arg1 intake 695:700 an average daily intake 678:700 an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d 678:749 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 15 104 theme fiber-rich 2385:2394 arg1 diets 2396:2400 the fiber-rich diets 2381:2400 the fiber-rich diets 2381:2400 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 4 105 theme multiparous 780:790 arg1 sows 792:795 48 multiparous sows 777:795 48 multiparous sows 777:795 A total of 48 multiparous sows were stratified by body weight at mating (day 0) and assigned to one of the four diets throughout gestation. 36637127 12 106 theme intake 1866:1871 arg1 intake 1866:1871 gross energy intake 1853:1871 gross energy intake 1853:1871 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 12 106 theme intake 1866:1871 arg1 % 1848:1848 53-72% 1843:1848 53-72% of gross energy intake 1843:1871 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 5 107 theme dilution 1020:1027 arg1 technique 1029:1037 the deuterium oxide dilution technique 1000:1037 the deuterium oxide dilution technique 1000:1037 Body weight and backfat were measured, and body pools of fat and protein were estimated using the deuterium oxide dilution technique at day 0, 30 and 60. 36637127 14 108 theme 14 2325:2326 arg1 % 2327:2327 % 2327:2327 % 2327:2327 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 14 109 theme N 2231:2231 arg1 loss 2233:2236 the lowest and highest N loss 2208:2236 loss 2233:2236 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 8 110 theme nutrients 1211:1219 arg1 ATTD 1203:1206 The ATTD 1199:1206 The ATTD of nutrients 1199:1219 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 6 111 theme grab 1094:1097 arg1 samples 1099:1105 urine and fecal grab samples 1078:1105 urine and fecal grab samples 1078:1105 On day 30 and 60, urine and fecal grab samples were obtained. 36637127 10 112 theme fed 1658:1660 arg1 sows 1662:1665 PKE fed sows 1654:1665 PKE fed sows 1654:1665 The ATTD of all nutrients except NSP was lowest in PKE fed sows and highest, except for N, in sows fed the SBP diet. 36637127 2 113 theme energy 493:498 arg1 metabolism 463:472 whole-body metabolism 452:472 whole-body metabolism 452:472 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 2 113 theme energy 493:498 arg1 utilization 478:488 utilization 478:488 utilization 478:488 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 3 114 theme daily 689:693 arg1 intake 695:700 an average daily intake 678:700 an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d 678:749 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 13 115 dep respectively 2150:2161 arg1 < 2166:2166 P < 0.001 2164:2172 P < 0.001 2164:2172 Energy for maintenance accounted for the majority of the heat production and the total energy retention was lowest and highest in the SBP and PKE fed sows, with a retention of 3.3 MJ/d and 13.3 MJ/d, respectively (P < 0.001). 36637127 9 116 theme lignin 1460:1465 arg1 intake 1450:1455 intake 1450:1455 intake of lignin (P < 0.001) 1450:1477 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 12 117 theme energy 1859:1864 arg1 intake 1866:1871 gross energy intake 1853:1871 gross energy intake 1853:1871 Sows lost most energy as heat (53-72% of gross energy intake), followed by energy in feces (15-17%), urine (3-4%) and methane (0.5-0.9%). 36637127 2 118 theme total 360:364 arg1 ATTD 387:390 ATTD 387:390 ATTD 387:390 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 2 118 theme total 360:364 arg1 digestibility 372:384 the apparent total tract digestibility 347:384 the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets 347:434 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 9 119 dep correlated 1521:1530 arg1 < 1535:1535 P < 0.001 1533:1541 P < 0.001 1533:1541 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 9 119 dep correlated 1521:1530 arg1 negatively 1509:1518 negatively 1509:1518 negatively 1509:1518 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 9 120 theme P 1468:1468 arg1 < 1470:1470 P < 0.001 1468:1476 P < 0.001 1468:1476 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 9 120 theme P 1468:1468 arg1 lignin 1460:1465 lignin 1460:1465 lignin (P < 0.001) 1460:1477 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 8 121 theme < 1251:1251 arg1 P 1249:1249 P < 0.001 1249:1257 P < 0.001 1249:1257 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 8 121 theme < 1251:1251 arg1 treatments 1237:1246 treatments 1237:1246 treatments (P < 0.001) 1237:1258 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 0 122 theme fiber-rich 18:27 arg1 supplements 29:39 four fiber-rich supplements 13:39 four fiber-rich supplements 13:39 Influence of four fiber-rich supplements on digestibility of energy and nutrients and utilization of energy and nitrogen in early and mid-gestating sows. 36637127 14 123 theme body 2352:2355 arg1 protein 2357:2363 body protein 2352:2363 body protein 2352:2363 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 14 123 theme body 2352:2355 arg1 % 2334:2334 14% to 26% 2325:2334 14% to 26% 2325:2334 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 14 124 theme fed 2286:2288 arg1 sows 2290:2293 SBP fed sows 2282:2293 SBP fed sows (50-63%, respectively) 2282:2316 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 5 125 theme fat 963:965 arg1 pools 954:958 body pools 949:958 body pools of fat and protein 949:977 Body weight and backfat were measured, and body pools of fat and protein were estimated using the deuterium oxide dilution technique at day 0, 30 and 60. 36637127 14 126 dep lowest 2212:2217 arg1 relative 2239:2246 relative 2239:2246 relative 2239:2246 Sows lost most N through urine, the lowest and highest N loss (relative to intake) was observed in SH and SBP fed sows (50-63%, respectively), while 14% to 26% was retained as body protein. 36637127 15 127 from % 2494:2494 arg1 diets 2519:2523 all four fiber-rich diets 2499:2523 all four fiber-rich diets 2499:2523 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 6 128 theme urine 1078:1082 arg1 samples 1099:1105 urine and fecal grab samples 1078:1105 urine and fecal grab samples 1078:1105 On day 30 and 60, urine and fecal grab samples were obtained. 36637127 1 129 theme growing 288:294 arg1 pigs 296:299 growing pigs 288:299 growing pigs 288:299 The digestibility of energy and nutrients in fiber-rich diets depends greatly on the fiber source but most data are from studies with growing pigs. 36637127 15 130 theme TF 2543:2544 arg1 content 2546:2552 the high TF content 2534:2552 the high TF content in the diets 2534:2565 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 15 131 from content 2546:2552 arg1 diets 2561:2565 the diets 2557:2565 the diets 2557:2565 In conclusion, the fiber-rich diets were utilized efficiently by gestating sows with respect to energy with ATTD values above 82% in all four fiber-rich diets, whereas the high TF content in the diets compromised the N utilization in gestating sows. 36637127 2 132 theme fiber-rich 419:428 arg1 diets 430:434 different fiber-rich diets 409:434 different fiber-rich diets 409:434 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 8 133 theme % 1331:1331 arg1 -units 1332:1337 up to +/- 3.3%-units 1318:1337 up to +/- 3.3%-units 1318:1337 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 9 134 theme N 1494:1494 arg1 ATTP 1486:1489 ATTP 1486:1489 ATTP of N 1486:1494 The ATTD of energy was highly negatively correlated with intake of lignin (P < 0.001), while ATTP of N was highest (negatively) correlated (P < 0.001) with intake of insoluble non-starch polysaccharides (NSP). 36637127 8 135 theme matter 1283:1288 arg1 digestibility 1290:1302 in vivo organic matter digestibility 1267:1302 in vivo organic matter digestibility 1267:1302 The ATTD of nutrients differed across treatments (P < 0.001), while in vivo organic matter digestibility deviated with up to +/- 3.3%-units from in vitro enzyme digestibility of organic matter. 36637127 3 136 theme soy 590:592 arg1 hulls 594:598 soy hulls 590:598 soy hulls (SH) 590:603 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 3 136 theme soy 590:592 arg1 SH 601:602 SH 601:602 SH 601:602 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 2 137 from digestibility 372:384 arg1 diets 430:434 different fiber-rich diets 409:434 different fiber-rich diets 409:434 The purpose of this study was to investigate the apparent total tract digestibility (ATTD) of nutrients in different fiber-rich diets and to quantify whole-body metabolism and utilization of energy and nitrogen (N) in gestating sows. 36637127 3 138 theme palm 606:609 arg1 PKE 629:631 PKE 629:631 PKE 629:631 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 3 138 theme palm 606:609 arg1 expellers 618:626 palm kernel expellers 606:626 palm kernel expellers (PKE) 606:632 Four fiber-rich diets based on sugar beet pulp (SBP), soy hulls (SH), palm kernel expellers (PKE) or a mixed fiber (MF) were formulated, with an average daily intake of total fiber (TF) of 471, 507, 651 and 437 g/d, respectively. 36637127 5 139 theme oxide 1014:1018 arg1 technique 1029:1037 the deuterium oxide dilution technique 1000:1037 the deuterium oxide dilution technique 1000:1037 Body weight and backfat were measured, and body pools of fat and protein were estimated using the deuterium oxide dilution technique at day 0, 30 and 60. 35485198 8 0 from side-chains 1429:1439 arg1 wall 1480:1483 the primary cell wall 1463:1483 the primary cell wall 1463:1483 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 5 1 theme necrotrophic 798:809 arg1 cinerea 836:842 the necrotrophic fungal pathogen Botrytis cinerea 794:842 the necrotrophic fungal pathogen Botrytis cinerea 794:842 BXL4 localized to the apoplast and was induced upon infection with the necrotrophic fungal pathogen Botrytis cinerea in a jasmonoyl isoleucine-dependent manner. 35485198 1 2 theme microbial 172:180 arg1 pathogens 182:190 microbial pathogens 172:190 microbial pathogens 172:190 Plant cell walls constitute physical barriers that restrict access of microbial pathogens to the contents of plant cells. 35485198 6 3 theme conditional 982:992 arg1 lines 1009:1013 conditional overexpression lines 982:1013 conditional overexpression lines 982:1013 The bxl4 mutants showed a reduced resistance to B. cinerea, while resistance was increased in conditional overexpression lines. 35485198 1 4 theme pathogens 182:190 arg1 access 162:167 access 162:167 access of microbial pathogens to the contents of plant cells 162:221 Plant cell walls constitute physical barriers that restrict access of microbial pathogens to the contents of plant cells. 35485198 4 5 from influence 566:574 arg1 immunity 593:600 plant immunity 587:600 plant immunity 587:600 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 6 6 theme bxl4 892:895 arg1 mutants 897:903 The bxl4 mutants 888:903 The bxl4 mutants 888:903 The bxl4 mutants showed a reduced resistance to B. cinerea, while resistance was increased in conditional overexpression lines. 35485198 7 7 theme mutant 1099:1104 arg1 phenotype 1106:1114 a bxl1 mutant phenotype 1092:1114 a bxl1 mutant phenotype 1092:1114 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 4 8 theme lines 720:724 arg1 use 687:689 use 687:689 use of mutant and overexpression lines 687:724 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 4 9 theme overexpression 705:718 arg1 lines 720:724 overexpression lines 705:724 overexpression lines 705:724 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 8 10 theme pathogen 1323:1330 arg1 attack 1332:1337 pathogen attack 1323:1337 pathogen attack 1323:1337 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 8 11 from removal 1397:1403 arg1 wall 1480:1483 the primary cell wall 1463:1483 the primary cell wall 1463:1483 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 4 12 theme BXL4 674:677 arg1 localization 635:646 subcellular localization 623:646 subcellular localization 623:646 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 4 12 theme BXL4 674:677 arg1 activity 662:669 enzymatic activity 652:669 enzymatic activity 652:669 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 5 13 theme fungal 811:816 arg1 cinerea 836:842 the necrotrophic fungal pathogen Botrytis cinerea 794:842 the necrotrophic fungal pathogen Botrytis cinerea 794:842 BXL4 localized to the apoplast and was induced upon infection with the necrotrophic fungal pathogen Botrytis cinerea in a jasmonoyl isoleucine-dependent manner. 35485198 4 14 theme enzymatic 652:660 arg1 activity 662:669 enzymatic activity 652:669 enzymatic activity 652:669 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 7 15 theme bxl1 1094:1097 arg1 phenotype 1106:1114 a bxl1 mutant phenotype 1092:1114 a bxl1 mutant phenotype 1092:1114 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 3 16 theme Arabidopsis 443:453 arg1 thaliana 468:475 Arabidopsis (Arabidopsis thaliana) 443:476 Arabidopsis (Arabidopsis thaliana) 443:476 BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. 35485198 0 17 theme wall-localized 5:18 arg1 BETA-XYLOSIDASE4 20:35 Cell wall-localized BETA-XYLOSIDASE4 0:35 Cell wall-localized BETA-XYLOSIDASE4 0:35 Cell wall-localized BETA-XYLOSIDASE4 contributes to immunity of Arabidopsis against Botrytis cinerea. 35485198 1 18 theme Plant 102:106 arg1 walls 113:117 Plant cell walls 102:117 Plant cell walls 102:117 Plant cell walls constitute physical barriers that restrict access of microbial pathogens to the contents of plant cells. 35485198 3 19 theme gene 428:431 arg1 family 433:438 a seven-member gene family 413:438 a seven-member gene family 413:438 BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. 35485198 0 20 theme Cell 0:3 arg1 BETA-XYLOSIDASE4 20:35 Cell wall-localized BETA-XYLOSIDASE4 0:35 Cell wall-localized BETA-XYLOSIDASE4 0:35 Cell wall-localized BETA-XYLOSIDASE4 contributes to immunity of Arabidopsis against Botrytis cinerea. 35485198 8 21 theme primary 1467:1473 arg1 wall 1480:1483 the primary cell wall 1463:1483 the primary cell wall 1463:1483 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 1 22 theme cell 108:111 arg1 walls 113:117 Plant cell walls 102:117 Plant cell walls 102:117 Plant cell walls constitute physical barriers that restrict access of microbial pathogens to the contents of plant cells. 35485198 3 23 theme family 433:438 arg1 protein 502:508 a protein 500:508 a protein (BXL1) involved in cell wall remodeling 500:548 BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. 35485198 3 23 theme family 433:438 arg1 one 479:481 one 479:481 one 479:481 BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. 35485198 3 23 theme family 433:438 arg1 family 433:438 a seven-member gene family 413:438 a seven-member gene family 413:438 BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. 35485198 4 24 dep localization 635:646 arg1 the 619:621 the 619:621 the 619:621 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 5 25 with infection 779:787 arg1 cinerea 836:842 the necrotrophic fungal pathogen Botrytis cinerea 794:842 the necrotrophic fungal pathogen Botrytis cinerea 794:842 BXL4 localized to the apoplast and was induced upon infection with the necrotrophic fungal pathogen Botrytis cinerea in a jasmonoyl isoleucine-dependent manner. 35485198 7 26 contain has 1150:1152 arg1 BXL4 1145:1148 BXL4 1145:1148 BXL4 1145:1148 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 7 26 contain has 1150:1152 arg2 activity 1188:1195 both xylosidase and arabinosidase activity 1154:1195 both xylosidase and arabinosidase activity 1154:1195 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 3 27 theme cell 529:532 arg1 remodeling 539:548 cell wall remodeling 529:548 cell wall remodeling 529:548 BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. 35485198 8 28 from arabinose 1408:1416 arg1 wall 1480:1483 the primary cell wall 1463:1483 the primary cell wall 1463:1483 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 1 29 theme plant 211:215 arg1 cells 217:221 plant cells 211:221 plant cells 211:221 Plant cell walls constitute physical barriers that restrict access of microbial pathogens to the contents of plant cells. 35485198 8 30 from wall 1480:1483 arg1 removal 1397:1403 removal 1397:1403 removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall 1397:1483 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 7 31 theme epidermal 1068:1076 arg1 cells 1078:1082 Arabidopsis seed coat epidermal cells 1046:1082 Arabidopsis seed coat epidermal cells 1046:1082 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 8 32 theme side-chains 1429:1439 arg1 removal 1397:1403 removal 1397:1403 removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall 1397:1483 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 3 33 theme wall 534:537 arg1 remodeling 539:548 cell wall remodeling 529:548 cell wall remodeling 529:548 BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. 35485198 1 34 theme cells 217:221 arg1 contents 199:206 the contents 195:206 the contents of plant cells 195:221 Plant cell walls constitute physical barriers that restrict access of microbial pathogens to the contents of plant cells. 35485198 7 35 theme Arabidopsis 1046:1056 arg1 cells 1078:1082 Arabidopsis seed coat epidermal cells 1046:1082 Arabidopsis seed coat epidermal cells 1046:1082 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 8 36 theme xylose 1422:1427 arg1 side-chains 1429:1439 xylose side-chains 1422:1439 xylose side-chains 1422:1439 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 5 37 theme jasmonoyl 849:857 arg1 manner 880:885 a jasmonoyl isoleucine-dependent manner 847:885 a jasmonoyl isoleucine-dependent manner 847:885 BXL4 localized to the apoplast and was induced upon infection with the necrotrophic fungal pathogen Botrytis cinerea in a jasmonoyl isoleucine-dependent manner. 35485198 5 38 theme pathogen 818:825 arg1 cinerea 836:842 the necrotrophic fungal pathogen Botrytis cinerea 794:842 the necrotrophic fungal pathogen Botrytis cinerea 794:842 BXL4 localized to the apoplast and was induced upon infection with the necrotrophic fungal pathogen Botrytis cinerea in a jasmonoyl isoleucine-dependent manner. 35485198 3 39 theme seven-member 415:426 arg1 family 433:438 a seven-member gene family 413:438 a seven-member gene family 413:438 BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. 35485198 6 40 theme B. 936:937 arg1 cinerea 939:945 B. cinerea 936:945 B. cinerea 936:945 The bxl4 mutants showed a reduced resistance to B. cinerea, while resistance was increased in conditional overexpression lines. 35485198 7 41 theme seed 1058:1061 arg1 cells 1078:1082 Arabidopsis seed coat epidermal cells 1046:1082 Arabidopsis seed coat epidermal cells 1046:1082 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 8 42 theme polysaccharides 1444:1458 arg1 arabinose 1408:1416 arabinose 1408:1416 arabinose 1408:1416 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 8 42 theme polysaccharides 1444:1458 arg1 side-chains 1429:1439 xylose side-chains 1422:1439 xylose side-chains 1422:1439 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 3 43 theme Arabidopsis 456:466 arg1 thaliana 468:475 Arabidopsis (Arabidopsis thaliana) 443:476 Arabidopsis (Arabidopsis thaliana) 443:476 BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. 35485198 0 44 theme Arabidopsis 64:74 arg1 immunity 52:59 immunity 52:59 immunity of Arabidopsis against Botrytis cinerea 52:99 Cell wall-localized BETA-XYLOSIDASE4 contributes to immunity of Arabidopsis against Botrytis cinerea. 35485198 7 45 theme arabinosidase 1174:1186 arg1 activity 1188:1195 both xylosidase and arabinosidase activity 1154:1195 both xylosidase and arabinosidase activity 1154:1195 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 7 46 theme BXL4 1038:1041 arg1 expression 1024:1033 Ectopic expression 1016:1033 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells 1016:1082 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 2 47 theme cell 236:239 arg1 wall 241:244 The primary cell wall 224:244 The primary cell wall of multicellular plants 224:268 The primary cell wall of multicellular plants predominantly consists of cellulose, hemicellulose, and pectin, and its composition can change upon stress. 35485198 7 48 theme Ectopic 1016:1022 arg1 expression 1024:1033 Ectopic expression 1016:1033 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells 1016:1082 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 1 49 theme physical 130:137 arg1 barriers 139:146 physical barriers 130:146 physical barriers that restrict access of microbial pathogens to the contents of plant cells 130:221 Plant cell walls constitute physical barriers that restrict access of microbial pathogens to the contents of plant cells. 35485198 7 50 theme coat 1063:1066 arg1 cells 1078:1082 Arabidopsis seed coat epidermal cells 1046:1082 Arabidopsis seed coat epidermal cells 1046:1082 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 2 51 theme primary 228:234 arg1 wall 241:244 The primary cell wall 224:244 The primary cell wall of multicellular plants 224:268 The primary cell wall of multicellular plants predominantly consists of cellulose, hemicellulose, and pectin, and its composition can change upon stress. 35485198 6 52 theme reduced 914:920 arg1 resistance 922:931 a reduced resistance 912:931 a reduced resistance to B. cinerea 912:945 The bxl4 mutants showed a reduced resistance to B. cinerea, while resistance was increased in conditional overexpression lines. 35485198 4 53 theme mutant 694:699 arg1 use 687:689 use 687:689 use of mutant and overexpression lines 687:724 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 8 54 theme B. 1373:1374 arg1 cinerea 1376:1382 B. cinerea 1373:1382 B. cinerea 1373:1382 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 4 55 theme BXL4 579:582 arg1 influence 566:574 the influence 562:574 the influence of BXL4 on plant immunity 562:600 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 8 56 theme cell 1475:1478 arg1 wall 1480:1483 the primary cell wall 1463:1483 the primary cell wall 1463:1483 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 8 57 theme arabinose 1408:1416 arg1 removal 1397:1403 removal 1397:1403 removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall 1397:1483 We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall. 35485198 0 58 theme Botrytis 84:91 arg1 cinerea 93:99 Botrytis cinerea 84:99 Botrytis cinerea 84:99 Cell wall-localized BETA-XYLOSIDASE4 contributes to immunity of Arabidopsis against Botrytis cinerea. 35485198 5 59 theme Botrytis 827:834 arg1 cinerea 836:842 the necrotrophic fungal pathogen Botrytis cinerea 794:842 the necrotrophic fungal pathogen Botrytis cinerea 794:842 BXL4 localized to the apoplast and was induced upon infection with the necrotrophic fungal pathogen Botrytis cinerea in a jasmonoyl isoleucine-dependent manner. 35485198 2 60 theme plants 263:268 arg1 wall 241:244 The primary cell wall 224:244 The primary cell wall of multicellular plants 224:268 The primary cell wall of multicellular plants predominantly consists of cellulose, hemicellulose, and pectin, and its composition can change upon stress. 35485198 3 61 from family 433:438 arg1 thaliana 468:475 Arabidopsis (Arabidopsis thaliana) 443:476 Arabidopsis (Arabidopsis thaliana) 443:476 BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. 35485198 5 62 theme isoleucine-dependent 859:878 arg1 manner 880:885 a jasmonoyl isoleucine-dependent manner 847:885 a jasmonoyl isoleucine-dependent manner 847:885 BXL4 localized to the apoplast and was induced upon infection with the necrotrophic fungal pathogen Botrytis cinerea in a jasmonoyl isoleucine-dependent manner. 35485198 4 63 theme subcellular 623:633 arg1 localization 635:646 subcellular localization 623:646 subcellular localization 623:646 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 4 64 theme plant 587:591 arg1 immunity 593:600 plant immunity 587:600 plant immunity 587:600 We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. 35485198 7 65 theme xylosidase 1159:1168 arg1 activity 1188:1195 both xylosidase and arabinosidase activity 1154:1195 both xylosidase and arabinosidase activity 1154:1195 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 2 66 theme multicellular 249:261 arg1 plants 263:268 multicellular plants 249:268 multicellular plants 249:268 The primary cell wall of multicellular plants predominantly consists of cellulose, hemicellulose, and pectin, and its composition can change upon stress. 35485198 7 67 from expression 1024:1033 arg1 cells 1078:1082 Arabidopsis seed coat epidermal cells 1046:1082 Arabidopsis seed coat epidermal cells 1046:1082 Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. 35485198 6 68 theme overexpression 994:1007 arg1 lines 1009:1013 conditional overexpression lines 982:1013 conditional overexpression lines 982:1013 The bxl4 mutants showed a reduced resistance to B. cinerea, while resistance was increased in conditional overexpression lines. 37084644 0 0 theme C 100:100 arg1 viruses 102:108 transmitted/founder HIV-1 subtype C viruses 66:108 transmitted/founder HIV-1 subtype C viruses 66:108 Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses. 37084644 6 1 theme chronic 875:881 arg1 infection 883:891 chronic infection 875:891 chronic infection 875:891 Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. 37084644 6 2 dep in 923:924 arg1 vitro 926:930 vitro 926:930 vitro 926:930 Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. 37084644 0 3 theme subtype 92:98 arg1 viruses 102:108 transmitted/founder HIV-1 subtype C viruses 66:108 transmitted/founder HIV-1 subtype C viruses 66:108 Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses. 37084644 6 4 theme in 923:924 arg1 capacity 944:951 heterogenous in vitro replicative capacity 910:951 heterogenous in vitro replicative capacity 910:951 Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. 37084644 5 5 dep subtype 709:715 arg1 C. 717:718 C. 717:718 C. 717:718 All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. 37084644 8 6 with viruses 1128:1134 arg1 envelopes 1149:1157 compact envelopes 1141:1157 compact envelopes 1141:1157 Our findings suggest MTF transmission may select viruses with compact envelopes. 37084644 6 7 theme heterogenous 910:921 arg1 capacity 944:951 heterogenous in vitro replicative capacity 910:951 heterogenous in vitro replicative capacity 910:951 Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. 37084644 3 8 theme In-Fusion-based 526:540 arg1 cloning 542:548 In-Fusion-based cloning 526:548 In-Fusion-based cloning 526:548 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 0 9 theme viruses 102:108 arg1 clones 56:61 infectious molecular clones 35:61 infectious molecular clones of transmitted/founder HIV-1 subtype C viruses 35:108 Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses. 37084644 5 10 theme non-recombinant 693:707 arg1 subtype 709:715 non-recombinant subtype 693:715 non-recombinant subtype C. Three of the 5 T/F clones 693:744 All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. 37084644 3 11 theme infection 510:518 arg1 year 502:505 one year 498:505 one year of infection using In-Fusion-based cloning 498:548 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 7 12 contain had 1002:1004 arg2 glycoproteins 1018:1030 shorter Env glycoproteins 1006:1030 shorter Env glycoproteins 1006:1030 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 7 12 contain had 1002:1004 arg1 viruses 994:1000 T/F viruses 990:1000 T/F viruses 990:1000 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 7 12 contain had 1002:1004 arg2 sites 1065:1069 fewer N-linked glycosylation sites 1036:1069 fewer N-linked glycosylation sites 1036:1069 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 8 13 dep suggest 1092:1098 arg1 select 1121:1126 select 1121:1126 suggest MTF transmission may select viruses with compact envelopes 1092:1157 Our findings suggest MTF transmission may select viruses with compact envelopes. 37084644 0 14 theme clones 56:61 arg1 characterization 15:30 characterization 15:30 characterization 15:30 Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses. 37084644 0 14 theme clones 56:61 arg1 Generation 0:9 Generation 0:9 Generation 0:9 Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses. 37084644 6 15 theme infection 883:891 arg1 clones 893:898 Transmitted/founder and chronic infection clones 851:898 Transmitted/founder and chronic infection clones 851:898 Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. 37084644 3 16 from transmission 467:478 arg1 clones 485:490 clones 485:490 clones 485:490 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 16 from transmission 467:478 arg1 clones 351:356 full-length clones 339:356 full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; 339:479 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 7 17 theme shorter 1006:1012 arg1 glycoproteins 1018:1030 shorter Env glycoproteins 1006:1030 shorter Env glycoproteins 1006:1030 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 3 18 theme heterosexual 433:444 arg1 transmission 467:478 heterosexual male-to-female (MTF) transmission 433:478 heterosexual male-to-female (MTF) transmission 433:478 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 18 theme heterosexual 433:444 arg1 MTF 462:464 MTF 462:464 MTF 462:464 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 19 theme stage 392:396 arg1 AHI 423:425 AHI 423:425 AHI 423:425 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 19 theme stage 392:396 arg1 infection 412:420 Fiebig stage I acute HIV-1 infection 385:420 Fiebig stage I acute HIV-1 infection (AHI) 385:426 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 5 20 theme chronic 752:758 arg1 clones 760:765 3 chronic clones 750:765 3 chronic clones tested 750:772 All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. 37084644 5 21 theme clones 739:744 arg1 subtype 709:715 non-recombinant subtype 693:715 non-recombinant subtype C. Three of the 5 T/F clones 693:744 All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. 37084644 3 22 theme I 398:398 arg1 AHI 423:425 AHI 423:425 AHI 423:425 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 22 theme I 398:398 arg1 infection 412:420 Fiebig stage I acute HIV-1 infection 385:420 Fiebig stage I acute HIV-1 infection (AHI) 385:426 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 8 23 theme MTF 1100:1102 arg1 transmission 1104:1115 MTF transmission 1100:1115 MTF transmission 1100:1115 Our findings suggest MTF transmission may select viruses with compact envelopes. 37084644 4 24 theme infection 627:635 arg1 clones 637:642 six chronic infection clones 615:642 six chronic infection clones 615:642 Eighteen full-length T/F clones were generated from 9 women and six chronic infection clones were from 2 individuals. 37084644 3 25 theme Fiebig 385:390 arg1 AHI 423:425 AHI 423:425 AHI 423:425 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 25 theme Fiebig 385:390 arg1 infection 412:420 Fiebig stage I acute HIV-1 infection 385:420 Fiebig stage I acute HIV-1 infection (AHI) 385:426 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 4 26 theme T/F 572:574 arg1 clones 576:581 Eighteen full-length T/F clones 551:581 Eighteen full-length T/F clones 551:581 Eighteen full-length T/F clones were generated from 9 women and six chronic infection clones were from 2 individuals. 37084644 3 27 theme biological 290:299 arg1 nature 301:306 the biological nature 286:306 the biological nature of T/F viruses 286:321 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 1 28 theme genetic 115:121 arg1 diversity 123:131 The genetic diversity 111:131 The genetic diversity of HIV 111:138 The genetic diversity of HIV impedes vaccine development. 37084644 4 29 theme chronic 619:625 arg1 clones 637:642 six chronic infection clones 615:642 six chronic infection clones 615:642 Eighteen full-length T/F clones were generated from 9 women and six chronic infection clones were from 2 individuals. 37084644 0 30 theme molecular 46:54 arg1 clones 56:61 infectious molecular clones 35:61 infectious molecular clones of transmitted/founder HIV-1 subtype C viruses 35:108 Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses. 37084644 4 31 theme full-length 560:570 arg1 clones 576:581 Eighteen full-length T/F clones 551:581 Eighteen full-length T/F clones 551:581 Eighteen full-length T/F clones were generated from 9 women and six chronic infection clones were from 2 individuals. 37084644 6 32 theme Transmitted/founder 851:869 arg1 clones 893:898 Transmitted/founder and chronic infection clones 851:898 Transmitted/founder and chronic infection clones 851:898 Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. 37084644 6 33 theme type 971:974 arg1 interferon 978:987 type I interferon 971:987 type I interferon 971:987 Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. 37084644 3 34 theme male-to-female 446:459 arg1 transmission 467:478 heterosexual male-to-female (MTF) transmission 433:478 heterosexual male-to-female (MTF) transmission 433:478 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 34 theme male-to-female 446:459 arg1 MTF 462:464 MTF 462:464 MTF 462:464 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 0 35 theme infectious 35:44 arg1 clones 56:61 infectious molecular clones 35:61 infectious molecular clones of transmitted/founder HIV-1 subtype C viruses 35:108 Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses. 37084644 2 36 theme viral 185:189 arg1 properties 191:200 the viral properties 181:200 the viral properties of transmitted/founder (T/F) variants 181:238 Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. 37084644 5 37 theme cell 839:842 arg1 entry 844:848 cell entry 839:848 cell entry 839:848 All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. 37084644 5 38 theme 5 T/F 733:737 arg1 clones 739:744 the 5 T/F clones 729:744 the 5 T/F clones 729:744 All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. 37084644 3 39 theme acute 400:404 arg1 AHI 423:425 AHI 423:425 AHI 423:425 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 39 theme acute 400:404 arg1 infection 412:420 Fiebig stage I acute HIV-1 infection 385:420 Fiebig stage I acute HIV-1 infection (AHI) 385:426 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 40 theme T/F 311:313 arg1 viruses 315:321 T/F viruses 311:321 T/F viruses 311:321 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 41 theme full-length 339:349 arg1 clones 351:356 full-length clones 339:356 full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; 339:479 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 7 42 theme fewer 1036:1040 arg1 sites 1065:1069 fewer N-linked glycosylation sites 1036:1069 fewer N-linked glycosylation sites 1036:1069 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 7 43 link N-linked 1042:1049 arg1 sites 1065:1069 fewer N-linked glycosylation sites 1036:1069 fewer N-linked glycosylation sites 1036:1069 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 3 44 theme HIV-1 406:410 arg1 AHI 423:425 AHI 423:425 AHI 423:425 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 44 theme HIV-1 406:410 arg1 infection 412:420 Fiebig stage I acute HIV-1 infection 385:420 Fiebig stage I acute HIV-1 infection (AHI) 385:426 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 7 45 gly glycoproteins 1018:1030 arg1 glycoproteins 1018:1030 shorter Env glycoproteins 1006:1030 shorter Env glycoproteins 1006:1030 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 3 46 theme viruses 315:321 arg1 nature 301:306 the biological nature 286:306 the biological nature of T/F viruses 286:321 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 2 47 theme variants 231:238 arg1 properties 191:200 the viral properties 181:200 the viral properties of transmitted/founder (T/F) variants 181:238 Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. 37084644 7 48 theme Env 1014:1016 arg1 glycoproteins 1018:1030 shorter Env glycoproteins 1006:1030 shorter Env glycoproteins 1006:1030 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 3 49 from women 363:367 arg1 clones 485:490 clones 485:490 clones 485:490 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 3 49 from women 363:367 arg1 clones 351:356 full-length clones 339:356 full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; 339:479 To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. 37084644 7 50 theme N-linked 1042:1049 arg1 sites 1065:1069 fewer N-linked glycosylation sites 1036:1069 fewer N-linked glycosylation sites 1036:1069 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 2 51 theme T/F 226:228 arg1 variants 231:238 transmitted/founder (T/F) variants 205:238 transmitted/founder (T/F) variants 205:238 Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. 37084644 1 52 theme HIV 136:138 arg1 diversity 123:131 The genetic diversity 111:131 The genetic diversity of HIV 111:138 The genetic diversity of HIV impedes vaccine development. 37084644 7 53 theme glycosylation 1051:1063 arg1 sites 1065:1069 fewer N-linked glycosylation sites 1036:1069 fewer N-linked glycosylation sites 1036:1069 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 5 54 theme utilised 810:817 arg1 coreceptor 824:833 utilised CCR5 coreceptor 810:833 utilised CCR5 coreceptor for cell entry 810:848 All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. 37084644 8 55 theme compact 1141:1147 arg1 envelopes 1149:1157 compact envelopes 1141:1157 compact envelopes 1141:1157 Our findings suggest MTF transmission may select viruses with compact envelopes. 37084644 7 56 gly glycosylation 1051:1063 arg2 sites 1065:1069 fewer N-linked glycosylation sites 1036:1069 fewer N-linked glycosylation sites 1036:1069 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 37084644 0 57 theme HIV-1 86:90 arg1 viruses 102:108 transmitted/founder HIV-1 subtype C viruses 66:108 transmitted/founder HIV-1 subtype C viruses 66:108 Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses. 37084644 2 58 theme transmitted/founder 205:223 arg1 variants 231:238 transmitted/founder (T/F) variants 205:238 transmitted/founder (T/F) variants 205:238 Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. 37084644 2 59 theme vaccine 261:267 arg1 target 269:274 a common vaccine target 252:274 a common vaccine target 252:274 Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. 37084644 5 60 theme CCR5 819:822 arg1 coreceptor 824:833 utilised CCR5 coreceptor 810:833 utilised CCR5 coreceptor for cell entry 810:848 All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. 37084644 1 61 theme vaccine 148:154 arg1 development 156:166 vaccine development 148:166 vaccine development 148:166 The genetic diversity of HIV impedes vaccine development. 37084644 0 62 theme transmitted/founder 66:84 arg1 viruses 102:108 transmitted/founder HIV-1 subtype C viruses 66:108 transmitted/founder HIV-1 subtype C viruses 66:108 Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses. 37084644 6 63 theme replicative 932:942 arg1 capacity 944:951 heterogenous in vitro replicative capacity 910:951 heterogenous in vitro replicative capacity 910:951 Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. 37084644 2 64 theme common 254:259 arg1 target 269:274 a common vaccine target 252:274 a common vaccine target 252:274 Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. 37084644 7 65 theme T/F 990:992 arg1 viruses 994:1000 T/F viruses 990:1000 T/F viruses 990:1000 T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. 36693065 7 0 theme enzymes 1156:1162 arg1 levels 1130:1135 transcript levels 1119:1135 transcript levels of iron-containing enzymes 1119:1162 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 2 1 theme fluctuating 330:340 arg1 concentrations 347:360 fluctuating iron concentrations 330:360 fluctuating iron concentrations 330:360 Numerous studies have been conducted to characterize the effect of iron on algae and how algae cope with fluctuating iron concentrations. 36693065 8 2 theme actinomycin 1285:1295 arg1 D 1297:1297 The transcription inhibitor actinomycin D 1257:1297 The transcription inhibitor actinomycin D 1257:1297 The transcription inhibitor actinomycin D was used to understand the underlying mechanisms of the decrease of the iron-responsive transcripts and to determine their half-lives. 36693065 7 3 theme transcript 1119:1128 arg1 levels 1130:1135 transcript levels 1119:1135 transcript levels of iron-containing enzymes 1119:1162 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 5 4 theme iron 846:849 arg1 photosynthesis 806:819 photosynthesis 806:819 photosynthesis 806:819 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 5 4 theme iron 846:849 arg1 transport 851:859 iron transport 846:859 iron transport 846:859 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 1 5 theme iron 155:158 arg1 concentrations 160:173 iron concentrations 155:173 iron concentrations 155:173 In large areas of the ocean, iron concentrations are insufficient to promote phytoplankton growth. 36693065 12 6 theme sudden 2080:2085 arg1 changes 2087:2093 sudden changes 2080:2093 sudden changes in iron concentrations 2080:2116 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 5 7 theme NanoString 695:704 arg1 platform 706:713 the NanoString platform 691:713 the NanoString platform 691:713 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 12 8 from context 1960:1966 arg1 understanding 1916:1928 a detailed understanding 1905:1928 a detailed understanding of diatom cell biology in the context of iron fertilization response 1905:1997 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 10 9 theme iron-responsive 1615:1629 arg1 transcripts 1631:1641 Four iron-responsive transcripts 1610:1641 Four iron-responsive transcripts 1610:1641 Four iron-responsive transcripts showed statistically significant differences in their decay rates between the iron-recovery samples and the actD treatment. 36693065 0 10 theme transcripts 113:123 arg1 decay 88:92 rapid decay 82:92 rapid decay of iron-responsive transcripts 82:123 Short-term response to iron resupply in an iron-limited open ocean diatom reveals rapid decay of iron-responsive transcripts. 36693065 2 11 theme iron 292:295 arg1 effect 282:287 the effect 278:287 the effect of iron on algae 278:304 Numerous studies have been conducted to characterize the effect of iron on algae and how algae cope with fluctuating iron concentrations. 36693065 12 12 theme oceanic 2045:2051 arg1 responses 2060:2068 oceanic diatom responses 2045:2068 oceanic diatom responses 2045:2068 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 10 13 theme decay 1697:1701 arg1 rates 1703:1707 their decay rates 1691:1707 their decay rates 1691:1707 Four iron-responsive transcripts showed statistically significant differences in their decay rates between the iron-recovery samples and the actD treatment. 36693065 4 14 theme Thalassiosira 655:667 arg1 diatom 647:652 an iron-starved open ocean diatom 620:652 an iron-starved open ocean diatom 620:652 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 36693065 4 14 theme Thalassiosira 655:667 arg1 oceanica 669:676 Thalassiosira oceanica 655:676 Thalassiosira oceanica 655:676 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 36693065 5 15 theme time 746:749 arg1 series 751:756 a high-resolution time series 728:756 a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors 728:893 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 5 16 from series 751:756 arg1 transcripts 764:774 54 transcripts 761:774 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors 761:893 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 2 17 theme Numerous 225:232 arg1 studies 234:240 Numerous studies 225:240 Numerous studies 225:240 Numerous studies have been conducted to characterize the effect of iron on algae and how algae cope with fluctuating iron concentrations. 36693065 1 18 theme phytoplankton 203:215 arg1 growth 217:222 phytoplankton growth 203:222 phytoplankton growth 203:222 In large areas of the ocean, iron concentrations are insufficient to promote phytoplankton growth. 36693065 8 19 theme transcription 1261:1273 arg1 D 1297:1297 The transcription inhibitor actinomycin D 1257:1297 The transcription inhibitor actinomycin D 1257:1297 The transcription inhibitor actinomycin D was used to understand the underlying mechanisms of the decrease of the iron-responsive transcripts and to determine their half-lives. 36693065 10 20 theme significant 1664:1674 arg1 differences 1676:1686 statistically significant differences 1650:1686 statistically significant differences in their decay rates between the iron-recovery samples and the actD treatment 1650:1764 Four iron-responsive transcripts showed statistically significant differences in their decay rates between the iron-recovery samples and the actD treatment. 36693065 7 21 theme iron 1079:1082 arg1 uptake 1084:1089 iron uptake 1079:1089 iron uptake 1079:1089 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 7 22 theme replacement 1236:1246 arg1 enzymes 1248:1254 their iron-free replacement enzymes 1220:1254 their iron-free replacement enzymes 1220:1254 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 9 23 theme cellular 1517:1524 arg1 repressor 1526:1534 cellular repressor 1517:1534 cellular repressor of EA1-stimulated genes (CREGx2) 1517:1567 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 1 24 theme large 129:133 arg1 areas 135:139 large areas 129:139 large areas of the ocean 129:152 In large areas of the ocean, iron concentrations are insufficient to promote phytoplankton growth. 36693065 0 25 theme open 56:59 arg1 diatom 67:72 an iron-limited open ocean diatom 40:72 an iron-limited open ocean diatom 40:72 Short-term response to iron resupply in an iron-limited open ocean diatom reveals rapid decay of iron-responsive transcripts. 36693065 9 26 theme genes 1554:1558 arg1 dismutase 1454:1462 Mn-superoxide dismutase 1440:1462 Mn-superoxide dismutase (Mn-SOD) 1440:1471 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 9 26 theme genes 1554:1558 arg1 PETE 1488:1491 PETE 1488:1491 PETE 1488:1491 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 9 26 theme genes 1554:1558 arg1 Mn-SOD 1465:1470 Mn-SOD 1465:1470 Mn-SOD 1465:1470 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 9 26 theme genes 1554:1558 arg1 repressor 1526:1534 cellular repressor 1517:1534 cellular repressor of EA1-stimulated genes (CREGx2) 1517:1567 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 9 26 theme genes 1554:1558 arg1 ferredoxin 1495:1504 ferredoxin 1495:1504 ferredoxin (PETF) 1495:1511 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 9 26 theme genes 1554:1558 arg1 plastocyanin 1474:1485 plastocyanin 1474:1485 plastocyanin (PETE) 1474:1492 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 9 26 theme genes 1554:1558 arg1 PETF 1507:1510 PETF 1507:1510 PETF 1507:1510 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 8 27 theme iron-responsive 1371:1385 arg1 transcripts 1387:1397 the iron-responsive transcripts 1367:1397 the iron-responsive transcripts 1367:1397 The transcription inhibitor actinomycin D was used to understand the underlying mechanisms of the decrease of the iron-responsive transcripts and to determine their half-lives. 36693065 7 28 theme fastest 991:997 arg1 decrease 1025:1032 the decrease 1021:1032 the decrease 1021:1032 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 7 28 theme fastest 991:997 arg1 response 999:1006 The fastest response 987:1006 The fastest response observed 987:1015 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 1 29 theme ocean 148:152 arg1 areas 135:139 large areas 129:139 large areas of the ocean 129:152 In large areas of the ocean, iron concentrations are insufficient to promote phytoplankton growth. 36693065 7 30 from decrease 1183:1190 arg1 levels 1130:1135 transcript levels 1119:1135 transcript levels of iron-containing enzymes 1119:1162 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 7 30 from decrease 1183:1190 arg1 levels 1210:1215 the transcript levels 1195:1215 the transcript levels of their iron-free replacement enzymes 1195:1254 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 11 31 theme mRNA 1850:1853 arg1 stability 1855:1863 mRNA stability 1850:1863 mRNA stability 1850:1863 These differences suggest regulatory mechanisms influencing gene transcription and mRNA stability. 36693065 0 32 theme rapid 82:86 arg1 decay 88:92 rapid decay 82:92 rapid decay of iron-responsive transcripts 82:123 Short-term response to iron resupply in an iron-limited open ocean diatom reveals rapid decay of iron-responsive transcripts. 36693065 1 33 from areas 135:139 arg1 insufficient 179:190 insufficient 179:190 insufficient 179:190 In large areas of the ocean, iron concentrations are insufficient to promote phytoplankton growth. 36693065 12 34 theme iron 1971:1974 arg1 response 1990:1997 iron fertilization response 1971:1997 iron fertilization response 1971:1997 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 1 35 from insufficient 179:190 arg1 areas 135:139 large areas 129:139 large areas of the ocean 129:152 In large areas of the ocean, iron concentrations are insufficient to promote phytoplankton growth. 36693065 3 36 theme diatom-dominated 429:444 arg1 blooms 452:457 diatom-dominated algal blooms 429:457 diatom-dominated algal blooms 429:457 Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. 36693065 0 37 theme Short-term 0:9 arg1 response 11:18 Short-term response 0:18 Short-term response to iron resupply in an iron-limited open ocean diatom 0:72 Short-term response to iron resupply in an iron-limited open ocean diatom reveals rapid decay of iron-responsive transcripts. 36693065 12 38 theme response 1990:1997 arg1 context 1960:1966 the context 1956:1966 the context of iron fertilization response 1956:1997 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 3 39 theme Fertilization 363:375 arg1 experiments 377:387 Fertilization experiments 363:387 Fertilization experiments in low-iron areas 363:405 Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. 36693065 7 40 from increase 1107:1114 arg1 levels 1130:1135 transcript levels 1119:1135 transcript levels of iron-containing enzymes 1119:1162 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 7 40 from increase 1107:1114 arg1 levels 1210:1215 the transcript levels 1195:1215 the transcript levels of their iron-free replacement enzymes 1195:1254 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 3 41 theme laboratory 471:480 arg1 studies 482:488 laboratory studies 471:488 laboratory studies on diatoms comparing low- and high-iron conditions 471:539 Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. 36693065 4 42 theme short-term 564:573 arg1 response 584:591 the short-term temporal response 560:591 the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica 560:676 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 36693065 3 43 from studies 482:488 arg1 diatoms 493:499 diatoms 493:499 diatoms comparing low- and high-iron conditions 493:539 Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. 36693065 12 44 theme cell 1940:1943 arg1 biology 1945:1951 diatom cell biology 1933:1951 diatom cell biology in the context of iron fertilization response 1933:1997 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 2 45 dep characterize 265:276 arg1 cope 320:323 cope 320:323 cope with fluctuating iron concentrations 320:360 Numerous studies have been conducted to characterize the effect of iron on algae and how algae cope with fluctuating iron concentrations. 36693065 0 46 theme iron-limited 43:54 arg1 diatom 67:72 an iron-limited open ocean diatom 40:72 an iron-limited open ocean diatom 40:72 Short-term response to iron resupply in an iron-limited open ocean diatom reveals rapid decay of iron-responsive transcripts. 36693065 4 47 theme iron-starved 623:634 arg1 diatom 647:652 an iron-starved open ocean diatom 620:652 an iron-starved open ocean diatom 620:652 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 36693065 4 47 theme iron-starved 623:634 arg1 oceanica 669:676 Thalassiosira oceanica 655:676 Thalassiosira oceanica 655:676 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 36693065 7 48 theme iron-containing 1140:1154 arg1 enzymes 1156:1162 iron-containing enzymes 1140:1162 iron-containing enzymes 1140:1162 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 2 49 theme iron 342:345 arg1 concentrations 347:360 fluctuating iron concentrations 330:360 fluctuating iron concentrations 330:360 Numerous studies have been conducted to characterize the effect of iron on algae and how algae cope with fluctuating iron concentrations. 36693065 6 50 theme immediate 943:951 arg1 response 953:960 an immediate response 940:960 an immediate response to the addition of iron 940:984 Nine transcripts were iron-responsive, with an immediate response to the addition of iron. 36693065 12 51 theme iron 2098:2101 arg1 concentrations 2103:2116 iron concentrations 2098:2116 iron concentrations 2098:2116 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 10 52 from differences 1676:1686 arg1 rates 1703:1707 their decay rates 1691:1707 their decay rates 1691:1707 Four iron-responsive transcripts showed statistically significant differences in their decay rates between the iron-recovery samples and the actD treatment. 36693065 4 53 theme iron 603:606 arg1 addition 608:615 iron addition 603:615 iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica 603:676 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 36693065 8 54 theme inhibitor 1275:1283 arg1 D 1297:1297 The transcription inhibitor actinomycin D 1257:1297 The transcription inhibitor actinomycin D 1257:1297 The transcription inhibitor actinomycin D was used to understand the underlying mechanisms of the decrease of the iron-responsive transcripts and to determine their half-lives. 36693065 7 55 from decrease 1025:1032 arg1 levels 1048:1053 transcript levels 1037:1053 transcript levels of proteins involved in iron uptake 1037:1089 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 8 56 used used 1303:1306 arg2 D 1297:1297 The transcription inhibitor actinomycin D 1257:1297 The transcription inhibitor actinomycin D 1257:1297 The transcription inhibitor actinomycin D was used to understand the underlying mechanisms of the decrease of the iron-responsive transcripts and to determine their half-lives. 36693065 4 57 theme ocean 641:645 arg1 diatom 647:652 an iron-starved open ocean diatom 620:652 an iron-starved open ocean diatom 620:652 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 36693065 4 57 theme ocean 641:645 arg1 oceanica 669:676 Thalassiosira oceanica 655:676 Thalassiosira oceanica 655:676 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 36693065 5 58 theme high-resolution 730:744 arg1 series 751:756 a high-resolution time series 728:756 a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors 728:893 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 5 59 link N-linked 822:829 arg1 photosynthesis 806:819 photosynthesis 806:819 photosynthesis 806:819 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 5 59 link N-linked 822:829 arg1 glycosylation 831:843 N-linked glycosylation 822:843 N-linked glycosylation 822:843 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 6 60 theme iron 981:984 arg1 addition 969:976 the addition 965:976 the addition of iron 965:984 Nine transcripts were iron-responsive, with an immediate response to the addition of iron. 36693065 12 61 theme diatom 2053:2058 arg1 responses 2060:2068 oceanic diatom responses 2045:2068 oceanic diatom responses 2045:2068 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 8 62 theme underlying 1326:1335 arg1 mechanisms 1337:1346 the underlying mechanisms 1322:1346 the underlying mechanisms of the decrease of the iron-responsive transcripts 1322:1397 The transcription inhibitor actinomycin D was used to understand the underlying mechanisms of the decrease of the iron-responsive transcripts and to determine their half-lives. 36693065 7 63 theme proteins 1058:1065 arg1 levels 1048:1053 transcript levels 1037:1053 transcript levels of proteins involved in iron uptake 1037:1089 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 7 64 theme transcript 1037:1046 arg1 levels 1048:1053 transcript levels 1037:1053 transcript levels of proteins involved in iron uptake 1037:1089 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 0 65 theme ocean 61:65 arg1 diatom 67:72 an iron-limited open ocean diatom 40:72 an iron-limited open ocean diatom 40:72 Short-term response to iron resupply in an iron-limited open ocean diatom reveals rapid decay of iron-responsive transcripts. 36693065 9 66 theme EA1-stimulated 1539:1552 arg1 genes 1554:1558 EA1-stimulated genes 1539:1558 EA1-stimulated genes (CREGx2) 1539:1567 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 9 66 theme EA1-stimulated 1539:1552 arg1 CREGx2 1561:1566 CREGx2 1561:1566 CREGx2 1561:1566 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 2 67 from effect 282:287 arg1 algae 300:304 algae 300:304 algae 300:304 Numerous studies have been conducted to characterize the effect of iron on algae and how algae cope with fluctuating iron concentrations. 36693065 8 68 theme decrease 1355:1362 arg1 mechanisms 1337:1346 the underlying mechanisms 1322:1346 the underlying mechanisms of the decrease of the iron-responsive transcripts 1322:1397 The transcription inhibitor actinomycin D was used to understand the underlying mechanisms of the decrease of the iron-responsive transcripts and to determine their half-lives. 36693065 11 69 theme gene 1827:1830 arg1 transcription 1832:1844 gene transcription 1827:1844 gene transcription 1827:1844 These differences suggest regulatory mechanisms influencing gene transcription and mRNA stability. 36693065 7 70 theme enzymes 1248:1254 arg1 levels 1210:1215 the transcript levels 1195:1215 the transcript levels of their iron-free replacement enzymes 1195:1254 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 12 71 theme important 2012:2020 arg1 observations 2022:2033 important observations 2012:2033 important observations 2012:2033 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 0 72 from response 11:18 arg1 diatom 67:72 an iron-limited open ocean diatom 40:72 an iron-limited open ocean diatom 40:72 Short-term response to iron resupply in an iron-limited open ocean diatom reveals rapid decay of iron-responsive transcripts. 36693065 7 73 theme iron-free 1226:1234 arg1 enzymes 1248:1254 their iron-free replacement enzymes 1220:1254 their iron-free replacement enzymes 1220:1254 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 8 74 theme transcripts 1387:1397 arg1 decrease 1355:1362 the decrease 1351:1362 the decrease of the iron-responsive transcripts 1351:1397 The transcription inhibitor actinomycin D was used to understand the underlying mechanisms of the decrease of the iron-responsive transcripts and to determine their half-lives. 36693065 0 75 theme iron-responsive 97:111 arg1 transcripts 113:123 iron-responsive transcripts 97:123 iron-responsive transcripts 97:123 Short-term response to iron resupply in an iron-limited open ocean diatom reveals rapid decay of iron-responsive transcripts. 36693065 3 76 from experiments 377:387 arg1 areas 401:405 low-iron areas 392:405 low-iron areas 392:405 Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. 36693065 12 77 theme fertilization 1976:1988 arg1 response 1990:1997 iron fertilization response 1971:1997 iron fertilization response 1971:1997 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 7 78 theme transcript 1199:1208 arg1 levels 1210:1215 the transcript levels 1195:1215 the transcript levels of their iron-free replacement enzymes 1195:1254 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 9 79 theme average 1590:1596 arg1 half-lives 1598:1607 average half-lives 1590:1607 average half-lives 1590:1607 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 3 80 theme low-iron 392:399 arg1 areas 401:405 low-iron areas 392:405 low-iron areas 392:405 Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. 36693065 3 81 theme algal 446:450 arg1 blooms 452:457 diatom-dominated algal blooms 429:457 diatom-dominated algal blooms 429:457 Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. 36693065 0 82 theme iron 23:26 arg1 resupply 28:35 iron resupply 23:35 iron resupply 23:35 Short-term response to iron resupply in an iron-limited open ocean diatom reveals rapid decay of iron-responsive transcripts. 36693065 4 83 theme temporal 575:582 arg1 response 584:591 the short-term temporal response 560:591 the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica 560:676 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 36693065 7 84 theme simultaneous 1170:1181 arg1 decrease 1183:1190 a simultaneous decrease 1168:1190 a simultaneous decrease in the transcript levels of their iron-free replacement enzymes 1168:1254 The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. 36693065 12 85 from changes 2087:2093 arg1 concentrations 2103:2116 iron concentrations 2098:2116 iron concentrations 2098:2116 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 10 86 theme iron-recovery 1721:1733 arg1 samples 1735:1741 the iron-recovery samples 1717:1741 the iron-recovery samples 1717:1741 Four iron-responsive transcripts showed statistically significant differences in their decay rates between the iron-recovery samples and the actD treatment. 36693065 5 87 theme N-linked 822:829 arg1 photosynthesis 806:819 photosynthesis 806:819 photosynthesis 806:819 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 5 87 theme N-linked 822:829 arg1 glycosylation 831:843 N-linked glycosylation 822:843 N-linked glycosylation 822:843 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 12 88 from biology 1945:1951 arg1 context 1960:1966 the context 1956:1966 the context of iron fertilization response 1956:1997 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 12 89 theme diatom 1933:1938 arg1 biology 1945:1951 diatom cell biology 1933:1951 diatom cell biology in the context of iron fertilization response 1933:1997 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 12 90 from understanding 1916:1928 arg1 context 1960:1966 the context 1956:1966 the context of iron fertilization response 1956:1997 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 11 91 theme regulatory 1793:1802 arg1 mechanisms 1804:1813 regulatory mechanisms 1793:1813 regulatory mechanisms influencing gene transcription and mRNA stability 1793:1863 These differences suggest regulatory mechanisms influencing gene transcription and mRNA stability. 36693065 3 92 theme high-iron 520:528 arg1 conditions 530:539 low- and high-iron conditions 511:539 low- and high-iron conditions 511:539 Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. 36693065 3 93 theme low- 511:514 arg1 conditions 530:539 low- and high-iron conditions 511:539 low- and high-iron conditions 511:539 Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. 36693065 12 94 theme biology 1945:1951 arg1 understanding 1916:1928 a detailed understanding 1905:1928 a detailed understanding of diatom cell biology in the context of iron fertilization response 1905:1997 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 12 95 theme detailed 1907:1914 arg1 understanding 1916:1928 a detailed understanding 1905:1928 a detailed understanding of diatom cell biology in the context of iron fertilization response 1905:1997 Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations. 36693065 10 96 theme actD 1751:1754 arg1 treatment 1756:1764 the actD treatment 1747:1764 the actD treatment 1747:1764 Four iron-responsive transcripts showed statistically significant differences in their decay rates between the iron-recovery samples and the actD treatment. 36693065 9 97 theme Mn-superoxide 1440:1452 arg1 dismutase 1454:1462 Mn-superoxide dismutase 1440:1462 Mn-superoxide dismutase (Mn-SOD) 1440:1471 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 9 97 theme Mn-superoxide 1440:1452 arg1 Mn-SOD 1465:1470 Mn-SOD 1465:1470 Mn-SOD 1465:1470 Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. 36693065 5 98 theme transcription 873:885 arg1 factors 887:893 transcription factors 873:893 photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors 806:893 We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. 36693065 6 99 with iron-responsive 918:932 arg1 response 953:960 an immediate response 940:960 an immediate response to the addition of iron 940:984 Nine transcripts were iron-responsive, with an immediate response to the addition of iron. 36693065 4 100 theme open 636:639 arg1 diatom 647:652 an iron-starved open ocean diatom 620:652 an iron-starved open ocean diatom 620:652 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 36693065 4 100 theme open 636:639 arg1 oceanica 669:676 Thalassiosira oceanica 655:676 Thalassiosira oceanica 655:676 Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. 35356257 6 0 theme OGT 881:883 arg1 overview 869:876 an overview 866:876 an overview of OGT in 32 cancers using a large number of samples (n = 21,196) 866:942 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 4 1 theme Kaplan-Meier 565:576 arg1 curves 578:583 Kaplan-Meier curves 565:583 Kaplan-Meier curves 565:583 The univariate Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were applied to determine OGT's clinical relevance in cancers. 35356257 2 2 theme significance 263:274 arg1 understanding 233:245 the understanding 229:245 the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC 229:355 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 7 3 located found 1110:1114 arg1 levels 1141:1146 both mRNA and protein levels 1119:1146 both mRNA and protein levels in SCLC 1119:1154 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 7 3 located found 1110:1114 arg2 OGT 1102:1104 upregulated OGT 1090:1104 upregulated OGT 1090:1104 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 6 4 from time 836:839 arg1 field 848:852 the field 844:852 the field 844:852 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 2 5 theme O-linked 293:300 arg1 GlcNAc 323:328 GlcNAc 323:328 GlcNAc 323:328 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 2 5 theme O-linked 293:300 arg1 N-acetylglucosamine 302:320 O-linked N-acetylglucosamine 293:320 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC 293:355 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 4 6 theme characteristic 609:622 arg1 curves 624:629 characteristic curves 609:629 characteristic curves 609:629 The univariate Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were applied to determine OGT's clinical relevance in cancers. 35356257 10 7 theme OGT 1460:1462 arg1 expression 1446:1455 The high expression 1437:1455 The high expression of OGT in SCLC 1437:1470 The high expression of OGT in SCLC may result from the positive regulation of two transcription factors-DEK and XRN2. 35356257 2 8 theme mechanism 280:288 arg1 understanding 233:245 the understanding 229:245 the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC 229:355 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 6 9 theme large 907:911 arg1 number 913:918 a large number 905:918 a large number of samples (n = 21,196) 905:942 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 5 10 theme Spearman 698:705 arg1 correlation 707:717 The Spearman correlation 694:717 The Spearman correlation analysis 694:726 The Spearman correlation analysis and enrichment analysis were utilized to explore the underlying mechanisms of OGT in cancers. 35356257 7 11 theme upregulated 1090:1100 arg1 OGT 1102:1104 upregulated OGT 1090:1104 upregulated OGT 1090:1104 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 2 12 theme present 200:206 arg1 study 208:212 the present study 196:212 the present study 196:212 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 9 13 theme SCLC 1363:1366 arg1 prediction 1368:1377 SCLC prediction 1363:1377 SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88) 1363:1434 The research also identified OGT expression as a potential marker for SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88). 35356257 7 14 from levels 1141:1146 arg1 SCLC 1151:1154 SCLC 1151:1154 SCLC 1151:1154 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 1 15 theme small-cell 134:143 arg1 cancer 150:155 small-cell lung cancer 134:155 small-cell lung cancer (SCLC) 134:162 The clinical progression of small-cell lung cancer (SCLC) remains pessimistic. 35356257 1 15 theme small-cell 134:143 arg1 SCLC 158:161 SCLC 158:161 SCLC 158:161 The clinical progression of small-cell lung cancer (SCLC) remains pessimistic. 35356257 6 16 theme OGT 966:968 arg1 expression 970:979 distinct OGT expression 957:979 distinct OGT expression in 25 cancers 957:993 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 4 17 theme clinical 663:670 arg1 relevance 672:680 OGT's clinical relevance 657:680 OGT's clinical relevance in cancers 657:691 The univariate Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were applied to determine OGT's clinical relevance in cancers. 35356257 1 18 theme cancer 150:155 arg1 progression 119:129 The clinical progression 106:129 The clinical progression of small-cell lung cancer (SCLC) 106:162 The clinical progression of small-cell lung cancer (SCLC) remains pessimistic. 35356257 6 19 from expression 970:979 arg1 cancers 987:993 25 cancers 984:993 25 cancers 984:993 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 6 19 from expression 970:979 arg1 cancers 1027:1033 12 cancers 1024:1033 12 cancers 1024:1033 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 13 20 dep treatment 1773:1781 arg1 the 1769:1771 the 1769:1771 the 1769:1771 OGT may be an underlying biomarker for the treatment and identification of some cancers, including SCLC. 35356257 9 21 dep prediction 1368:1377 arg1 specificity = 0.86 1400:1417 specificity = 0.86 1400:1417 specificity = 0.86 1400:1417 The research also identified OGT expression as a potential marker for SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88). 35356257 9 21 dep prediction 1368:1377 arg1 AUC = 0.88 1424:1433 AUC = 0.88 1424:1433 AUC = 0.88 1424:1433 The research also identified OGT expression as a potential marker for SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88). 35356257 0 22 theme Lung 93:96 arg1 Cancer 98:103 Small-Cell Lung Cancer 82:103 Small-Cell Lung Cancer 82:103 Ogt Demonstrated Conspicuous Clinical Significance in Cancers, from Pan-Cancer to Small-Cell Lung Cancer. 35356257 7 23 dep CI 1173:1174 arg1 1.63 1183:1186 1.63 1183:1186 1.63 1183:1186 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 8 24 theme disease-free 1240:1251 arg1 interval 1253:1260 a more unfavorable disease-free interval 1221:1260 a more unfavorable disease-free interval for SCLC patients (p < 0.001) 1221:1290 Higher OGT levels represented a more unfavorable disease-free interval for SCLC patients (p < 0.001). 35356257 10 25 theme transcription 1519:1531 arg1 factors-DEK 1533:1543 two transcription factors-DEK 1515:1543 two transcription factors-DEK 1515:1543 The high expression of OGT in SCLC may result from the positive regulation of two transcription factors-DEK and XRN2. 35356257 5 26 theme enrichment 732:741 arg1 analysis 743:750 enrichment analysis 732:750 enrichment analysis 732:750 The Spearman correlation analysis and enrichment analysis were utilized to explore the underlying mechanisms of OGT in cancers. 35356257 5 27 used utilized 757:764 arg2 analysis 743:750 enrichment analysis 732:750 enrichment analysis 732:750 The Spearman correlation analysis and enrichment analysis were utilized to explore the underlying mechanisms of OGT in cancers. 35356257 5 27 used utilized 757:764 arg2 analysis 719:726 The Spearman correlation analysis 694:726 The Spearman correlation analysis 694:726 The Spearman correlation analysis and enrichment analysis were utilized to explore the underlying mechanisms of OGT in cancers. 35356257 3 28 theme Wilcoxon 358:365 arg1 tests 367:371 Wilcoxon tests 358:371 Wilcoxon tests 358:371 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 5 29 theme OGT 806:808 arg1 mechanisms 792:801 the underlying mechanisms 777:801 the underlying mechanisms of OGT in cancers 777:819 The Spearman correlation analysis and enrichment analysis were utilized to explore the underlying mechanisms of OGT in cancers. 35356257 0 30 theme Conspicuous 17:27 arg1 Significance 38:49 Conspicuous Clinical Significance 17:49 Conspicuous Clinical Significance 17:49 Ogt Demonstrated Conspicuous Clinical Significance in Cancers, from Pan-Cancer to Small-Cell Lung Cancer. 35356257 3 31 theme experimental 492:503 arg1 groups 517:522 the experimental and control groups 488:522 the experimental and control groups 488:522 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 8 32 theme OGT 1198:1200 arg1 levels 1202:1207 Higher OGT levels 1191:1207 Higher OGT levels 1191:1207 Higher OGT levels represented a more unfavorable disease-free interval for SCLC patients (p < 0.001). 35356257 3 33 theme mean 387:390 arg1 SMD 404:406 SMD 404:406 SMD 404:406 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 3 33 theme mean 387:390 arg1 difference 392:401 standardized mean difference 374:401 standardized mean difference (SMD) 374:407 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 4 34 theme univariate 529:538 arg1 analysis 555:562 The univariate Cox regression analysis 525:562 The univariate Cox regression analysis 525:562 The univariate Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were applied to determine OGT's clinical relevance in cancers. 35356257 8 35 theme p 1281:1281 arg1 < 1283:1283 p < 0.001 1281:1289 p < 0.001 1281:1289 Higher OGT levels represented a more unfavorable disease-free interval for SCLC patients (p < 0.001). 35356257 8 35 theme p 1281:1281 arg1 patients 1271:1278 SCLC patients 1266:1278 SCLC patients (p < 0.001) 1266:1290 Higher OGT levels represented a more unfavorable disease-free interval for SCLC patients (p < 0.001). 35356257 2 36 theme transferase 331:341 arg1 significance 263:274 clinical significance 254:274 clinical significance 254:274 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 2 36 theme transferase 331:341 arg1 mechanism 280:288 mechanism 280:288 mechanism 280:288 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 7 37 theme multiple 1072:1079 arg1 sources 1081:1087 multiple sources 1072:1087 multiple sources 1072:1087 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 12 38 theme conspicuous 1695:1705 arg1 significance 1716:1727 conspicuous clinical significance 1695:1727 conspicuous clinical significance 1695:1727 Herein, based on the analyses from pan-cancer to SCLC, OGT demonstrated conspicuous clinical significance. 35356257 6 39 theme first 830:834 arg1 time 836:839 the first time 826:839 the first time in the field 826:852 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 11 40 theme OGT 1610:1612 arg1 mechanisms 1596:1605 the underlying mechanisms 1581:1605 the underlying mechanisms of OGT in SCLC 1581:1620 We primarily investigated the underlying mechanisms of OGT in SCLC. 35356257 10 41 theme factors-DEK 1533:1543 arg1 regulation 1501:1510 the positive regulation 1488:1510 the positive regulation of two transcription factors-DEK and XRN2 1488:1552 The high expression of OGT in SCLC may result from the positive regulation of two transcription factors-DEK and XRN2. 35356257 12 42 from pan-cancer 1658:1667 arg1 analyses 1644:1651 the analyses 1640:1651 the analyses from pan-cancer to SCLC 1640:1675 Herein, based on the analyses from pan-cancer to SCLC, OGT demonstrated conspicuous clinical significance. 35356257 7 43 theme protein 1133:1139 arg1 levels 1141:1146 both mRNA and protein levels 1119:1146 both mRNA and protein levels in SCLC 1119:1154 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 3 44 theme level 464:468 arg1 differences 470:480 OGT level differences 460:480 OGT level differences among the experimental and control groups 460:522 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 4 45 from relevance 672:680 arg1 cancers 685:691 cancers 685:691 cancers 685:691 The univariate Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were applied to determine OGT's clinical relevance in cancers. 35356257 7 46 theme SMD = 0.93 1157:1166 arg1 CI 1173:1174 SMD = 0.93, 95% CI [0.24 1157:1180 CI 1173:1174 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 4 47 theme regression 544:553 arg1 analysis 555:562 The univariate Cox regression analysis 525:562 The univariate Cox regression analysis 525:562 The univariate Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were applied to determine OGT's clinical relevance in cancers. 35356257 3 48 theme control 509:515 arg1 groups 517:522 the experimental and control groups 488:522 the experimental and control groups 488:522 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 2 49 from transferase 331:341 arg1 SCLC 352:355 SCLC 352:355 SCLC 352:355 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 10 50 theme high 1441:1444 arg1 expression 1446:1455 The high expression 1437:1455 The high expression of OGT in SCLC 1437:1470 The high expression of OGT in SCLC may result from the positive regulation of two transcription factors-DEK and XRN2. 35356257 6 51 from effects 1013:1019 arg1 cancers 987:993 25 cancers 984:993 25 cancers 984:993 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 6 51 from effects 1013:1019 arg1 cancers 1027:1033 12 cancers 1024:1033 12 cancers 1024:1033 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 2 52 theme clinical 254:261 arg1 significance 263:274 clinical significance 254:274 clinical significance 254:274 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 13 53 theme cancers 1810:1816 arg1 identification 1787:1800 identification 1787:1800 identification 1787:1800 OGT may be an underlying biomarker for the treatment and identification of some cancers, including SCLC. 35356257 13 53 theme cancers 1810:1816 arg1 treatment 1773:1781 treatment 1773:1781 treatment 1773:1781 OGT may be an underlying biomarker for the treatment and identification of some cancers, including SCLC. 35356257 2 54 theme N-acetylglucosamine 302:320 arg1 OGT 344:346 OGT 344:346 OGT 344:346 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 2 54 theme N-acetylglucosamine 302:320 arg1 transferase 331:341 O-linked N-acetylglucosamine (GlcNAc) transferase 293:341 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC 293:355 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 9 55 theme OGT 1322:1324 arg1 expression 1326:1335 OGT expression 1322:1335 OGT expression 1322:1335 The research also identified OGT expression as a potential marker for SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88). 35356257 9 55 theme OGT 1322:1324 arg1 marker 1352:1357 a potential marker 1340:1357 a potential marker for SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88) 1340:1434 The research also identified OGT expression as a potential marker for SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88). 35356257 6 56 theme samples 923:929 arg1 number 913:918 a large number 905:918 a large number of samples (n = 21,196) 905:942 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 10 57 theme positive 1492:1499 arg1 regulation 1501:1510 the positive regulation 1488:1510 the positive regulation of two transcription factors-DEK and XRN2 1488:1552 The high expression of OGT in SCLC may result from the positive regulation of two transcription factors-DEK and XRN2. 35356257 9 58 theme potential 1342:1350 arg1 expression 1326:1335 OGT expression 1322:1335 OGT expression 1322:1335 The research also identified OGT expression as a potential marker for SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88). 35356257 9 58 theme potential 1342:1350 arg1 marker 1352:1357 a potential marker 1340:1357 a potential marker for SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88) 1340:1434 The research also identified OGT expression as a potential marker for SCLC prediction (sensitivity = 0.79, specificity = 0.86, and AUC = 0.88). 35356257 0 59 from Pan-Cancer 68:77 arg1 Cancers 54:60 Cancers 54:60 Cancers 54:60 Ogt Demonstrated Conspicuous Clinical Significance in Cancers, from Pan-Cancer to Small-Cell Lung Cancer. 35356257 7 60 theme mRNA 1124:1127 arg1 levels 1141:1146 both mRNA and protein levels 1119:1146 both mRNA and protein levels in SCLC 1119:1154 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 2 61 theme study 208:212 arg1 aim 189:191 The aim 185:191 The aim of the present study 185:212 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 1 62 theme clinical 110:117 arg1 progression 119:129 The clinical progression 106:129 The clinical progression of small-cell lung cancer (SCLC) 106:162 The clinical progression of small-cell lung cancer (SCLC) remains pessimistic. 35356257 2 63 link O-linked 293:300 arg1 GlcNAc 323:328 GlcNAc 323:328 GlcNAc 323:328 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 2 63 link O-linked 293:300 arg1 N-acetylglucosamine 302:320 O-linked N-acetylglucosamine 293:320 O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC 293:355 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 1 64 theme lung 145:148 arg1 cancer 150:155 small-cell lung cancer 134:155 small-cell lung cancer (SCLC) 134:162 The clinical progression of small-cell lung cancer (SCLC) remains pessimistic. 35356257 1 64 theme lung 145:148 arg1 SCLC 158:161 SCLC 158:161 SCLC 158:161 The clinical progression of small-cell lung cancer (SCLC) remains pessimistic. 35356257 2 65 from significance 263:274 arg1 SCLC 352:355 SCLC 352:355 SCLC 352:355 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 6 66 theme distinct 957:964 arg1 expression 970:979 distinct OGT expression 957:979 distinct OGT expression in 25 cancers 957:993 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 11 67 from mechanisms 1596:1605 arg1 SCLC 1617:1620 SCLC 1617:1620 SCLC 1617:1620 We primarily investigated the underlying mechanisms of OGT in SCLC. 35356257 8 68 theme Higher 1191:1196 arg1 levels 1202:1207 Higher OGT levels 1191:1207 Higher OGT levels 1191:1207 Higher OGT levels represented a more unfavorable disease-free interval for SCLC patients (p < 0.001). 35356257 13 69 theme underlying 1744:1753 arg1 biomarker 1755:1763 an underlying biomarker 1741:1763 an underlying biomarker for the treatment and identification of some cancers, including SCLC 1741:1832 OGT may be an underlying biomarker for the treatment and identification of some cancers, including SCLC. 35356257 13 69 theme underlying 1744:1753 arg1 OGT 1730:1732 OGT 1730:1732 OGT 1730:1732 OGT may be an underlying biomarker for the treatment and identification of some cancers, including SCLC. 35356257 0 70 theme Small-Cell 82:91 arg1 Cancer 98:103 Small-Cell Lung Cancer 82:103 Small-Cell Lung Cancer 82:103 Ogt Demonstrated Conspicuous Clinical Significance in Cancers, from Pan-Cancer to Small-Cell Lung Cancer. 35356257 5 71 from mechanisms 792:801 arg1 cancers 813:819 cancers 813:819 cancers 813:819 The Spearman correlation analysis and enrichment analysis were utilized to explore the underlying mechanisms of OGT in cancers. 35356257 2 72 from mechanism 280:288 arg1 SCLC 352:355 SCLC 352:355 SCLC 352:355 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 7 73 from sources 1081:1087 arg1 samples 1059:1065 950 samples 1055:1065 950 samples from multiple sources 1055:1087 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 2 74 dep significance 263:274 arg1 the 250:252 the 250:252 the 250:252 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 5 75 theme correlation 707:717 arg1 analysis 719:726 The Spearman correlation analysis 694:726 The Spearman correlation analysis 694:726 The Spearman correlation analysis and enrichment analysis were utilized to explore the underlying mechanisms of OGT in cancers. 35356257 7 76 dep found 1110:1114 arg1 CI 1173:1174 SMD = 0.93, 95% CI [0.24 1157:1180 CI 1173:1174 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 8 77 theme unfavorable 1228:1238 arg1 interval 1253:1260 a more unfavorable disease-free interval 1221:1260 a more unfavorable disease-free interval for SCLC patients (p < 0.001) 1221:1290 Higher OGT levels represented a more unfavorable disease-free interval for SCLC patients (p < 0.001). 35356257 6 78 theme prognosis 1003:1011 arg1 effects 1013:1019 its prognosis effects 999:1019 its prognosis effects in 12 cancers 999:1033 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35356257 0 79 theme Clinical 29:36 arg1 Significance 38:49 Conspicuous Clinical Significance 17:49 Conspicuous Clinical Significance 17:49 Ogt Demonstrated Conspicuous Clinical Significance in Cancers, from Pan-Cancer to Small-Cell Lung Cancer. 35356257 4 80 theme Cox 540:542 arg1 analysis 555:562 The univariate Cox regression analysis 525:562 The univariate Cox regression analysis 525:562 The univariate Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were applied to determine OGT's clinical relevance in cancers. 35356257 8 81 theme SCLC 1266:1269 arg1 < 1283:1283 p < 0.001 1281:1289 p < 0.001 1281:1289 Higher OGT levels represented a more unfavorable disease-free interval for SCLC patients (p < 0.001). 35356257 8 81 theme SCLC 1266:1269 arg1 patients 1271:1278 SCLC patients 1266:1278 SCLC patients (p < 0.001) 1266:1290 Higher OGT levels represented a more unfavorable disease-free interval for SCLC patients (p < 0.001). 35356257 10 82 theme XRN2 1549:1552 arg1 regulation 1501:1510 the positive regulation 1488:1510 the positive regulation of two transcription factors-DEK and XRN2 1488:1552 The high expression of OGT in SCLC may result from the positive regulation of two transcription factors-DEK and XRN2. 35356257 3 83 used utilized 440:447 arg2 difference 392:401 standardized mean difference 374:401 standardized mean difference (SMD) 374:407 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 3 83 used utilized 440:447 arg2 tests 429:433 Kruskal-Wallis tests 414:433 Kruskal-Wallis tests 414:433 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 3 83 used utilized 440:447 arg2 tests 367:371 Wilcoxon tests 358:371 Wilcoxon tests 358:371 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 3 83 used utilized 440:447 arg2 SMD 404:406 SMD 404:406 SMD 404:406 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 3 84 theme Kruskal-Wallis 414:427 arg1 tests 429:433 Kruskal-Wallis tests 414:433 Kruskal-Wallis tests 414:433 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 5 85 theme underlying 781:790 arg1 mechanisms 792:801 the underlying mechanisms 777:801 the underlying mechanisms of OGT in cancers 777:819 The Spearman correlation analysis and enrichment analysis were utilized to explore the underlying mechanisms of OGT in cancers. 35356257 12 86 theme clinical 1707:1714 arg1 significance 1716:1727 conspicuous clinical significance 1695:1727 conspicuous clinical significance 1695:1727 Herein, based on the analyses from pan-cancer to SCLC, OGT demonstrated conspicuous clinical significance. 35356257 2 87 from SCLC 352:355 arg1 significance 263:274 clinical significance 254:274 clinical significance 254:274 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 2 87 from SCLC 352:355 arg1 mechanism 280:288 mechanism 280:288 mechanism 280:288 The aim of the present study was to promote the understanding of the clinical significance and mechanism of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in SCLC. 35356257 3 88 theme standardized 374:385 arg1 SMD 404:406 SMD 404:406 SMD 404:406 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 3 88 theme standardized 374:385 arg1 difference 392:401 standardized mean difference 374:401 standardized mean difference (SMD) 374:407 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 3 89 theme OGT 460:462 arg1 differences 470:480 OGT level differences 460:480 OGT level differences among the experimental and control groups 460:522 Wilcoxon tests, standardized mean difference (SMD), and Kruskal-Wallis tests were utilized to compare OGT level differences among the experimental and control groups. 35356257 7 90 theme % 1171:1171 arg1 CI 1173:1174 SMD = 0.93, 95% CI [0.24 1157:1180 CI 1173:1174 Furthermore, using 950 samples from multiple sources, upregulated OGT was found in both mRNA and protein levels in SCLC (SMD = 0.93, 95% CI [0.24, 1.63]). 35356257 11 91 theme underlying 1585:1594 arg1 mechanisms 1596:1605 the underlying mechanisms 1581:1605 the underlying mechanisms of OGT in SCLC 1581:1620 We primarily investigated the underlying mechanisms of OGT in SCLC. 35356257 10 92 from expression 1446:1455 arg1 SCLC 1467:1470 SCLC 1467:1470 SCLC 1467:1470 The high expression of OGT in SCLC may result from the positive regulation of two transcription factors-DEK and XRN2. 35356257 6 93 from overview 869:876 arg1 cancers 891:897 32 cancers 888:897 32 cancers using a large number of samples (n = 21,196) 888:942 For the first time in the field, we provide an overview of OGT in 32 cancers using a large number of samples (n = 21,196), determining distinct OGT expression in 25 cancers and its prognosis effects in 12 cancers. 35304331 0 0 from role 8:11 arg1 homeostasis 61:71 energy homeostasis 54:71 energy homeostasis 54:71 A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis. 35304331 7 1 theme body 1137:1140 arg1 index 1147:1151 body mass index 1137:1151 body mass index 1137:1151 RESULTS First, we uncovered associations between GALNT2 gene variation, adiposity, and body mass index in humans. 35304331 9 2 from role 1447:1450 arg1 homeostasis 1473:1483 energy homeostasis 1466:1483 energy homeostasis 1466:1483 CONCLUSIONS This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor. 35304331 5 3 theme lipoprotein 899:909 arg1 metabolism 911:920 high-density lipoprotein metabolism 886:920 high-density lipoprotein metabolism 886:920 METHODS GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. 35304331 9 4 theme posttranslational 1568:1584 arg1 modification 1586:1597 posttranslational modification 1568:1597 posttranslational modification of the insulin receptor 1568:1621 CONCLUSIONS This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor. 35304331 5 5 theme GWAS 790:793 arg1 data 795:798 GWAS data 790:798 METHODS GWAS data from the UK Biobank 782:818 METHODS GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. 35304331 6 6 theme Experimental 923:934 arg1 data 936:939 Experimental data 923:939 Experimental data 923:939 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 7 7 theme gene 1106:1109 arg1 variation 1111:1119 GALNT2 gene variation 1099:1119 GALNT2 gene variation 1099:1119 RESULTS First, we uncovered associations between GALNT2 gene variation, adiposity, and body mass index in humans. 35304331 5 8 from changes 875:881 arg1 metabolism 911:920 high-density lipoprotein metabolism 886:920 high-density lipoprotein metabolism 886:920 METHODS GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. 35304331 2 9 theme established 380:390 arg1 roles 392:396 established roles 380:396 established roles in plasma lipid metabolism 380:423 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 5 10 theme high-density 886:897 arg1 metabolism 911:920 high-density lipoprotein metabolism 886:920 high-density lipoprotein metabolism 886:920 METHODS GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. 35304331 2 11 with glycosylation 340:352 arg1 roles 392:396 established roles 380:396 established roles in plasma lipid metabolism 380:423 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 6 12 from diet 1044:1047 arg1 studies 963:969 studies 963:969 studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet 963:1047 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 8 13 from adiposity 1294:1302 arg1 utilization 1370:1380 energy substrate utilization 1353:1380 energy substrate utilization 1353:1380 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 8 13 from adiposity 1294:1302 arg1 signaling 1328:1336 insulin signaling 1320:1336 insulin signaling 1320:1336 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 3 14 theme novel 549:553 arg1 disorder 566:573 a novel congenital disorder 547:573 a novel congenital disorder of glycosylation that affects development and body weight 547:631 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 3 14 theme novel 549:553 arg1 loss 460:463 loss 460:463 loss of GALNT2 in rodents, cattle, nonhuman primates, and humans 460:523 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 6 15 from mice 984:987 arg1 control 1023:1029 control 1023:1029 control 1023:1029 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 6 15 from mice 984:987 arg1 diet 1044:1047 high-fat diet 1035:1047 high-fat diet 1035:1047 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 8 16 theme decreased 1284:1292 arg1 adiposity 1294:1302 decreased adiposity 1284:1302 decreased adiposity 1284:1302 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 2 17 theme post-translational 292:309 arg1 modification 311:322 post-translational modification 292:322 post-translational modification 292:322 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 5 18 theme GALNT2 855:860 arg1 locus 862:866 the GALNT2 locus 851:866 the GALNT2 locus 851:866 METHODS GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. 35304331 8 19 theme novel 1211:1215 arg1 receptor 1197:1204 the insulin receptor 1185:1204 the insulin receptor 1185:1204 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 8 19 theme novel 1211:1215 arg1 substrate 1217:1225 a novel substrate 1209:1225 a novel substrate of GalNAc-T2 1209:1238 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 5 20 from Biobank 812:818 arg1 data 795:798 GWAS data 790:798 METHODS GWAS data from the UK Biobank 782:818 METHODS GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. 35304331 6 21 from littermates 1003:1013 arg1 control 1023:1029 control 1023:1029 control 1023:1029 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 6 21 from littermates 1003:1013 arg1 diet 1044:1047 high-fat diet 1035:1047 high-fat diet 1035:1047 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 2 22 from roles 392:396 arg1 metabolism 414:423 plasma lipid metabolism 401:423 plasma lipid metabolism 401:423 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 1 23 theme OBJECTIVE 74:82 arg1 regulator 192:200 a regulator 190:200 a regulator of high-density lipoprotein metabolism 190:239 OBJECTIVE GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. 35304331 1 23 theme OBJECTIVE 74:82 arg1 GALNT2 84:89 OBJECTIVE GALNT2 74:89 OBJECTIVE GALNT2 74:89 OBJECTIVE GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. 35304331 3 24 theme GALNT2 468:473 arg1 disorder 566:573 a novel congenital disorder 547:573 a novel congenital disorder of glycosylation that affects development and body weight 547:631 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 3 24 theme GALNT2 468:473 arg1 loss 460:463 loss 460:463 loss of GALNT2 in rodents, cattle, nonhuman primates, and humans 460:523 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 0 25 theme novel 2:6 arg1 role 8:11 A novel role 0:11 A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis 0:71 A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis. 35304331 6 26 theme Galnt2-/- 974:982 arg1 mice 984:987 Galnt2-/- mice 974:987 Galnt2-/- mice 974:987 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 6 27 from control 1023:1029 arg1 studies 963:969 studies 963:969 studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet 963:1047 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 9 28 theme local 1520:1524 arg1 effects 1526:1532 the local effects 1516:1532 the local effects of GalNAc-T2 1516:1545 CONCLUSIONS This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor. 35304331 9 29 theme energy 1466:1471 arg1 homeostasis 1473:1483 energy homeostasis 1466:1483 energy homeostasis 1466:1483 CONCLUSIONS This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor. 35304331 6 30 theme wild-type 993:1001 arg1 littermates 1003:1013 wild-type littermates 993:1013 wild-type littermates 993:1013 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 8 31 theme GalNAc-T2 1230:1238 arg1 receptor 1197:1204 the insulin receptor 1185:1204 the insulin receptor 1185:1204 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 8 31 theme GalNAc-T2 1230:1238 arg1 substrate 1217:1225 a novel substrate 1209:1225 a novel substrate of GalNAc-T2 1209:1238 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 2 32 theme O-linked 331:338 arg1 glycosylation 340:352 O-linked glycosylation 331:352 O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism 331:423 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 8 33 theme energy 1353:1358 arg1 utilization 1370:1380 energy substrate utilization 1353:1380 energy substrate utilization 1353:1380 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 2 34 theme lipid 408:412 arg1 metabolism 414:423 plasma lipid metabolism 401:423 plasma lipid metabolism 401:423 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 7 35 from variation 1111:1119 arg1 humans 1156:1161 humans 1156:1161 humans 1156:1161 RESULTS First, we uncovered associations between GALNT2 gene variation, adiposity, and body mass index in humans. 35304331 5 36 dep METHODS 782:788 arg1 data 795:798 GWAS data 790:798 METHODS GWAS data from the UK Biobank 782:818 METHODS GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. 35304331 9 37 theme novel 1441:1445 arg1 role 1447:1450 a novel role 1439:1450 a novel role for GALNT2 in energy homeostasis 1439:1483 CONCLUSIONS This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor. 35304331 3 38 theme congenital 555:564 arg1 disorder 566:573 a novel congenital disorder 547:573 a novel congenital disorder of glycosylation that affects development and body weight 547:631 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 3 38 theme congenital 555:564 arg1 loss 460:463 loss 460:463 loss of GALNT2 in rodents, cattle, nonhuman primates, and humans 460:523 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 8 39 from alterations 1305:1315 arg1 utilization 1370:1380 energy substrate utilization 1353:1380 energy substrate utilization 1353:1380 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 8 39 from alterations 1305:1315 arg1 signaling 1328:1336 insulin signaling 1320:1336 insulin signaling 1320:1336 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 8 40 theme Galnt2-/- 1261:1269 arg1 mice 1271:1274 Galnt2-/- mice 1261:1274 Galnt2-/- mice 1261:1274 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 3 41 theme glycosylation 578:590 arg1 disorder 566:573 a novel congenital disorder 547:573 a novel congenital disorder of glycosylation that affects development and body weight 547:631 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 3 41 theme glycosylation 578:590 arg1 loss 460:463 loss 460:463 loss of GALNT2 in rodents, cattle, nonhuman primates, and humans 460:523 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 7 42 theme GALNT2 1099:1104 arg1 variation 1111:1119 GALNT2 gene variation 1099:1119 GALNT2 gene variation 1099:1119 RESULTS First, we uncovered associations between GALNT2 gene variation, adiposity, and body mass index in humans. 35304331 1 43 theme polypeptide 101:111 arg1 N-acetylgalactosaminyltransferase 113:145 polypeptide N-acetylgalactosaminyltransferase 2 101:147 polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2) 101:159 OBJECTIVE GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. 35304331 1 43 theme polypeptide 101:111 arg1 GalNAc-T2 150:158 GalNAc-T2 150:158 GalNAc-T2 150:158 OBJECTIVE GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. 35304331 1 44 theme high-density 205:216 arg1 metabolism 230:239 high-density lipoprotein metabolism 205:239 high-density lipoprotein metabolism 205:239 OBJECTIVE GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. 35304331 0 45 theme dependent 27:35 arg1 glycosylation 37:49 GalNAc-T2 dependent glycosylation 17:49 GalNAc-T2 dependent glycosylation 17:49 A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis. 35304331 4 46 theme insulin 716:722 arg1 sensitivity 724:734 insulin sensitivity 716:734 insulin sensitivity 716:734 The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. 35304331 9 47 dep CONCLUSIONS 1405:1415 arg1 identifies 1428:1437 identifies 1428:1437 identifies a novel role for GALNT2 in energy homeostasis 1428:1483 CONCLUSIONS This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor. 35304331 8 48 theme insulin 1320:1326 arg1 signaling 1328:1336 insulin signaling 1320:1336 insulin signaling 1320:1336 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 4 49 theme other 680:684 arg1 abnormalities 666:678 metabolic abnormalities 656:678 metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, 656:758 The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. 35304331 1 50 theme lipoprotein 218:228 arg1 metabolism 230:239 high-density lipoprotein metabolism 205:239 high-density lipoprotein metabolism 205:239 OBJECTIVE GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. 35304331 7 51 from index 1147:1151 arg1 humans 1156:1161 humans 1156:1161 humans 1156:1161 RESULTS First, we uncovered associations between GALNT2 gene variation, adiposity, and body mass index in humans. 35304331 8 52 theme inactive 1389:1396 arg1 phase 1398:1402 the inactive phase 1385:1402 the inactive phase 1385:1402 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 1 53 theme metabolism 230:239 arg1 regulator 192:200 a regulator 190:200 a regulator of high-density lipoprotein metabolism 190:239 OBJECTIVE GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. 35304331 1 53 theme metabolism 230:239 arg1 GALNT2 84:89 OBJECTIVE GALNT2 74:89 OBJECTIVE GALNT2 74:89 OBJECTIVE GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. 35304331 7 54 theme mass 1142:1145 arg1 index 1147:1151 body mass index 1137:1151 body mass index 1137:1151 RESULTS First, we uncovered associations between GALNT2 gene variation, adiposity, and body mass index in humans. 35304331 9 55 theme insulin 1606:1612 arg1 receptor 1614:1621 the insulin receptor 1602:1621 the insulin receptor 1602:1621 CONCLUSIONS This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor. 35304331 0 56 theme energy 54:59 arg1 homeostasis 61:71 energy homeostasis 54:71 energy homeostasis 54:71 A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis. 35304331 9 57 theme receptor 1614:1621 arg1 modification 1586:1597 posttranslational modification 1568:1597 posttranslational modification of the insulin receptor 1568:1621 CONCLUSIONS This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor. 35304331 8 58 theme substrate 1360:1368 arg1 utilization 1370:1380 energy substrate utilization 1353:1380 energy substrate utilization 1353:1380 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 5 59 theme UK 809:810 arg1 Biobank 812:818 the UK Biobank 805:818 the UK Biobank 805:818 METHODS GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. 35304331 5 60 used used 824:827 arg2 METHODS 782:788 METHODS 782:788 METHODS GWAS data from the UK Biobank 782:818 METHODS GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. 35304331 2 61 theme proteins 366:373 arg1 glycosylation 340:352 O-linked glycosylation 331:352 O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism 331:423 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 9 62 theme GalNAc-T2 1537:1545 arg1 effects 1526:1532 the local effects 1516:1532 the local effects of GalNAc-T2 1516:1545 CONCLUSIONS This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor. 35304331 2 63 link O-linked 331:338 arg1 glycosylation 340:352 O-linked glycosylation 331:352 O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism 331:423 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 5 64 from variation 838:846 arg1 locus 862:866 the GALNT2 locus 851:866 the GALNT2 locus 851:866 METHODS GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. 35304331 2 65 theme secreted 357:364 arg1 proteins 366:373 secreted proteins 357:373 secreted proteins 357:373 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 6 66 from studies 963:969 arg1 mice 984:987 Galnt2-/- mice 974:987 Galnt2-/- mice 974:987 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 6 66 from studies 963:969 arg1 littermates 1003:1013 wild-type littermates 993:1013 wild-type littermates 993:1013 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 6 66 from studies 963:969 arg1 control 1023:1029 control 1023:1029 control 1023:1029 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 6 66 from studies 963:969 arg1 diet 1044:1047 high-fat diet 1035:1047 high-fat diet 1035:1047 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 4 67 theme energy 740:745 arg1 homeostasis 747:757 energy homeostasis 740:757 energy homeostasis 740:757 The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. 35304331 7 68 from adiposity 1122:1130 arg1 humans 1156:1161 humans 1156:1161 humans 1156:1161 RESULTS First, we uncovered associations between GALNT2 gene variation, adiposity, and body mass index in humans. 35304331 3 69 theme nonhuman 495:502 arg1 primates 504:511 nonhuman primates 495:511 nonhuman primates 495:511 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 8 70 from shift 1344:1348 arg1 utilization 1370:1380 energy substrate utilization 1353:1380 energy substrate utilization 1353:1380 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 8 70 from shift 1344:1348 arg1 signaling 1328:1336 insulin signaling 1320:1336 insulin signaling 1320:1336 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 2 71 dep glycosylation 340:352 arg1 i.e. 325:328 i.e. 325:328 i.e. 325:328 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 4 72 theme GALNT2 646:651 arg1 role 638:641 The role 634:641 The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, 634:758 The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. 35304331 3 73 theme body 621:624 arg1 weight 626:631 body weight 621:631 body weight 621:631 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 3 74 from loss 460:463 arg1 primates 504:511 nonhuman primates 495:511 nonhuman primates 495:511 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 3 74 from loss 460:463 arg1 humans 518:523 humans 518:523 humans 518:523 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 3 74 from loss 460:463 arg1 cattle 487:492 cattle 487:492 cattle 487:492 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 3 74 from loss 460:463 arg1 rodents 478:484 rodents 478:484 rodents 478:484 It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. 35304331 2 75 theme plasma 401:406 arg1 metabolism 414:423 plasma lipid metabolism 401:423 plasma lipid metabolism 401:423 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 4 76 theme metabolic 656:664 arg1 abnormalities 666:678 metabolic abnormalities 656:678 metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, 656:758 The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. 35304331 6 77 theme high-fat 1035:1042 arg1 diet 1044:1047 high-fat diet 1035:1047 high-fat diet 1035:1047 Experimental data were obtained through studies in Galnt2-/- mice and wild-type littermates on both control and high-fat diet. 35304331 2 78 gly glycosylation 340:352 arg1 proteins 366:373 secreted proteins 357:373 secreted proteins 357:373 GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. 35304331 4 79 from role 638:641 arg1 abnormalities 666:678 metabolic abnormalities 656:678 metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, 656:758 The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. 35304331 8 80 theme insulin 1189:1195 arg1 receptor 1197:1204 the insulin receptor 1185:1204 the insulin receptor 1185:1204 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 8 80 theme insulin 1189:1195 arg1 substrate 1217:1225 a novel substrate 1209:1225 a novel substrate of GalNAc-T2 1209:1238 In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. 35304331 4 81 theme plasma 691:696 arg1 sensitivity 724:734 insulin sensitivity 716:734 insulin sensitivity 716:734 The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. 35304331 4 81 theme plasma 691:696 arg1 homeostasis 747:757 energy homeostasis 740:757 energy homeostasis 740:757 The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. 35304331 4 81 theme plasma 691:696 arg1 lipids 698:703 plasma lipids 691:703 plasma lipids 691:703 The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. 36861967 0 0 theme stromal 84:90 arg1 progenitors 92:102 bone marrow stromal progenitors 72:102 bone marrow stromal progenitors 72:102 O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors. 36861967 7 1 theme factors 1294:1300 arg1 regulation 1266:1275 reciprocal O-GlcNAc regulation 1246:1275 reciprocal O-GlcNAc regulation 1246:1275 Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche. 36861967 7 2 theme osteogenic 1178:1187 arg1 differentiation 1204:1218 osteogenic and adipogenic differentiation 1178:1218 osteogenic and adipogenic differentiation of BMSCs 1178:1227 Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche. 36861967 0 3 theme marrow 77:82 arg1 progenitors 92:102 bone marrow stromal progenitors 72:102 bone marrow stromal progenitors 72:102 O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors. 36861967 6 4 from overproduction 1133:1146 arg1 mice 1151:1154 mice 1151:1154 mice 1151:1154 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 4 5 theme osteogenic 745:754 arg1 differentiation 756:770 osteogenic differentiation 745:770 osteogenic differentiation of BMSCs 745:779 By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. 36861967 6 6 theme marrow 1061:1066 arg1 adiposity 1068:1076 increased marrow adiposity 1051:1076 increased marrow adiposity 1051:1076 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 3 7 dep fate 626:629 arg1 the 606:608 the 606:608 the 606:608 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 6 8 theme B-cell 1100:1105 arg1 lymphopoiesis 1107:1119 defective B-cell lymphopoiesis 1090:1119 defective B-cell lymphopoiesis 1090:1119 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 6 9 theme increased 1051:1059 arg1 adiposity 1068:1076 increased marrow adiposity 1051:1076 increased marrow adiposity 1051:1076 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 0 10 theme progenitors 92:102 arg1 decision 41:48 fate decision 36:48 fate decision 36:48 O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors. 36861967 0 10 theme progenitors 92:102 arg1 function 60:67 niche function 54:67 niche function 54:67 O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors. 36861967 3 11 link O-linked 507:514 arg1 switch 585:590 a posttranslational switch 565:590 a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs) 565:682 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 11 link O-linked 507:514 arg1 modification 549:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 7 12 theme O-GlcNAc 1257:1264 arg1 regulation 1266:1275 reciprocal O-GlcNAc regulation 1246:1275 reciprocal O-GlcNAc regulation 1246:1275 Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche. 36861967 4 13 theme BMSCs 775:779 arg1 differentiation 756:770 osteogenic differentiation 745:770 osteogenic differentiation of BMSCs 745:779 By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. 36861967 4 13 theme BMSCs 775:779 arg1 expression 798:807 stromal IL-7 expression 785:807 stromal IL-7 expression 785:807 By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. 36861967 5 14 dep marrow 865:870 arg1 adipogenesis 872:883 adipogenesis 872:883 adipogenesis 872:883 In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. 36861967 5 15 theme cell 921:924 arg1 factor 926:931 myelopoietic stem cell factor 903:931 myelopoietic stem cell factor (SCF) 903:937 In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. 36861967 5 15 theme cell 921:924 arg1 SCF 934:936 SCF 934:936 SCF 934:936 In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. 36861967 7 16 theme differentiation 1204:1218 arg1 balance 1167:1173 the balance 1163:1173 the balance of osteogenic and adipogenic differentiation of BMSCs 1163:1227 Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche. 36861967 7 17 theme reciprocal 1246:1255 arg1 regulation 1266:1275 reciprocal O-GlcNAc regulation 1246:1275 reciprocal O-GlcNAc regulation 1246:1275 Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche. 36861967 2 18 theme skeletal 415:422 arg1 systems 442:448 skeletal and hematopoietic systems 415:448 skeletal and hematopoietic systems 415:448 Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. 36861967 6 19 from adiposity 1068:1076 arg1 mice 1151:1154 mice 1151:1154 mice 1151:1154 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 6 20 from transferase 990:1000 arg1 BMSCs 1011:1015 BMSCs 1011:1015 BMSCs 1011:1015 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 0 21 theme O-GlcNAc 0:7 arg1 glycosylation 9:21 O-GlcNAc glycosylation 0:21 O-GlcNAc glycosylation 0:21 O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors. 36861967 3 22 theme niche 635:639 arg1 function 641:648 niche function 635:648 niche function 635:648 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 1 23 theme hematopoietic 170:182 arg1 progenitors 184:194 hematopoietic progenitors 170:194 hematopoietic progenitors 170:194 In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. 36861967 0 24 theme fate 36:39 arg1 decision 41:48 fate decision 36:48 fate decision 36:48 O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors. 36861967 4 25 theme IL-7 793:796 arg1 expression 798:807 stromal IL-7 expression 785:807 stromal IL-7 expression 785:807 By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. 36861967 6 26 from lymphopoiesis 1107:1119 arg1 mice 1151:1154 mice 1151:1154 mice 1151:1154 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 3 27 theme differentiation 610:624 arg1 fate 626:629 differentiation fate 610:629 differentiation fate 610:629 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 28 theme early 653:657 arg1 cells 670:674 early BM stromal cells 653:674 early BM stromal cells (BMSCs) 653:682 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 28 theme early 653:657 arg1 BMSCs 677:681 BMSCs 677:681 BMSCs 677:681 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 29 theme intracellular 493:505 arg1 switch 585:590 a posttranslational switch 565:590 a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs) 565:682 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 29 theme intracellular 493:505 arg1 modification 549:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 2 30 theme definitive 319:328 arg1 hematopoiesis 330:342 definitive hematopoiesis 319:342 definitive hematopoiesis 319:342 Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. 36861967 6 31 theme impaired 1026:1033 arg1 formation 1040:1048 impaired bone formation 1026:1048 impaired bone formation 1026:1048 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 3 32 theme O-linked 507:514 arg1 switch 585:590 a posttranslational switch 565:590 a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs) 565:682 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 32 theme O-linked 507:514 arg1 modification 549:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 6 33 from formation 1040:1048 arg1 mice 1151:1154 mice 1151:1154 mice 1151:1154 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 5 34 theme factor 926:931 arg1 marrow 865:870 C/EBPβ-dependent marrow adipogenesis and expression 848:898 marrow 865:870 In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. 36861967 5 34 theme factor 926:931 arg1 expression 889:898 expression 889:898 expression 889:898 In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. 36861967 2 35 theme bone 241:244 arg1 growth 246:251 Perinatal bone growth 231:251 Perinatal bone growth 231:251 Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. 36861967 6 36 theme myeloid 1125:1131 arg1 overproduction 1133:1146 myeloid overproduction 1125:1146 myeloid overproduction 1125:1146 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 2 37 theme systems 442:448 arg1 development 400:410 the development 396:410 the development of skeletal and hematopoietic systems 396:448 Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. 36861967 5 38 theme C/EBPβ-dependent 848:863 arg1 marrow 865:870 C/EBPβ-dependent marrow adipogenesis and expression 848:898 marrow 865:870 In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. 36861967 7 39 theme hematopoietic 1335:1347 arg1 niche 1349:1353 the hematopoietic niche 1331:1353 the hematopoietic niche 1331:1353 Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche. 36861967 7 40 theme BMSCs 1223:1227 arg1 differentiation 1204:1218 osteogenic and adipogenic differentiation 1178:1218 osteogenic and adipogenic differentiation of BMSCs 1178:1227 Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche. 36861967 2 41 theme Perinatal 231:239 arg1 growth 246:251 Perinatal bone growth 231:251 Perinatal bone growth 231:251 Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. 36861967 1 42 theme bone-BM 210:216 arg1 homeostasis 218:228 bone-BM homeostasis 210:228 bone-BM homeostasis 210:228 In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. 36861967 7 43 theme adipogenic 1193:1202 arg1 differentiation 1204:1218 osteogenic and adipogenic differentiation 1178:1218 osteogenic and adipogenic differentiation of BMSCs 1178:1227 Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche. 36861967 6 44 theme defective 1090:1098 arg1 lymphopoiesis 1107:1119 defective B-cell lymphopoiesis 1090:1119 defective B-cell lymphopoiesis 1090:1119 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 6 45 theme bone 1035:1038 arg1 formation 1040:1048 impaired bone formation 1026:1048 impaired bone formation 1026:1048 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 3 46 theme O-GlcNAc 539:546 arg1 switch 585:590 a posttranslational switch 565:590 a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs) 565:682 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 46 theme O-GlcNAc 539:546 arg1 modification 549:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 0 47 theme niche 54:58 arg1 function 60:67 niche function 54:67 niche function 54:67 O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors. 36861967 3 48 theme BM 659:660 arg1 cells 670:674 early BM stromal cells 653:674 early BM stromal cells (BMSCs) 653:682 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 48 theme BM 659:660 arg1 BMSCs 677:681 BMSCs 677:681 BMSCs 677:681 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 49 theme β-N-acetylglucosamine 516:536 arg1 switch 585:590 a posttranslational switch 565:590 a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs) 565:682 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 49 theme β-N-acetylglucosamine 516:536 arg1 modification 549:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 5 50 theme myelopoietic 903:914 arg1 factor 926:931 myelopoietic stem cell factor 903:931 myelopoietic stem cell factor (SCF) 903:937 In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. 36861967 5 50 theme myelopoietic 903:914 arg1 SCF 934:936 SCF 934:936 SCF 934:936 In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. 36861967 3 51 theme posttranslational 567:583 arg1 switch 585:590 a posttranslational switch 565:590 a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs) 565:682 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 51 theme posttranslational 567:583 arg1 modification 549:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification 493:560 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 4 52 theme stromal 785:791 arg1 expression 798:807 stromal IL-7 expression 785:807 stromal IL-7 expression 785:807 By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. 36861967 0 53 theme bone 72:75 arg1 progenitors 92:102 bone marrow stromal progenitors 72:102 bone marrow stromal progenitors 72:102 O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors. 36861967 2 54 theme hematopoietic 428:440 arg1 systems 442:448 skeletal and hematopoietic systems 415:448 skeletal and hematopoietic systems 415:448 Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. 36861967 3 55 theme stromal 662:668 arg1 cells 670:674 early BM stromal cells 653:674 early BM stromal cells (BMSCs) 653:682 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 55 theme stromal 662:668 arg1 BMSCs 677:681 BMSCs 677:681 BMSCs 677:681 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 5 56 theme stem 916:919 arg1 factor 926:931 myelopoietic stem cell factor 903:931 myelopoietic stem cell factor (SCF) 903:937 In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. 36861967 5 56 theme stem 916:919 arg1 SCF 934:936 SCF 934:936 SCF 934:936 In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. 36861967 1 57 theme bone 142:145 arg1 marrow 147:152 bone marrow 142:152 the bone marrow (BM) stroma 138:164 In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. 36861967 1 57 theme bone 142:145 arg1 BM 155:156 BM 155:156 BM 155:156 In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. 36861967 6 58 theme O-GlcNAc 981:988 arg1 transferase 990:1000 O-GlcNAc transferase 981:1000 O-GlcNAc transferase (OGT) in BMSCs 981:1015 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 6 58 theme O-GlcNAc 981:988 arg1 OGT 1003:1005 OGT 1003:1005 OGT 1003:1005 Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. 36861967 3 59 theme cells 670:674 arg1 fate 626:629 differentiation fate 610:629 differentiation fate 610:629 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 3 59 theme cells 670:674 arg1 function 641:648 niche function 635:648 niche function 635:648 Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). 36861967 1 60 theme marrow 147:152 arg1 stroma 159:164 the bone marrow (BM) stroma 138:164 the bone marrow (BM) stroma 138:164 In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. 36861967 7 61 theme transcription 1280:1292 arg1 factors 1294:1300 transcription factors 1280:1300 transcription factors 1280:1300 Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche. 35462166 4 0 theme energy 1031:1036 arg1 transfer 1038:1045 a time-resolved fluorescence resonance energy transfer 992:1045 a time-resolved fluorescence resonance energy transfer 992:1045 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 5 1 theme downstream 1166:1175 arg1 HMOX2 1191:1195 HMOX2 1191:1195 HMOX2 1191:1195 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 5 1 theme downstream 1166:1175 arg1 GSTM3 1184:1188 GSTM3 1184:1188 GSTM3 1184:1188 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 5 1 theme downstream 1166:1175 arg1 genes 1177:1181 Nrf2 downstream genes 1161:1181 Nrf2 downstream genes 1161:1181 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 5 1 theme downstream 1166:1175 arg1 NQO1 1201:1204 NQO1 1201:1204 NQO1 1201:1204 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 6 2 theme scaffolds 1257:1265 arg1 discovery 1236:1244 The discovery 1232:1244 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position 1232:1322 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 6 3 theme pharmacokinetic 1433:1447 arg1 efficacy 1450:1457 efficacy 1450:1457 efficacy 1450:1457 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 3 4 dep benzene 738:744 arg1 the 734:736 the 734:736 the 734:736 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 4 5 theme resonance 1021:1029 arg1 transfer 1038:1045 a time-resolved fluorescence resonance energy transfer 992:1045 a time-resolved fluorescence resonance energy transfer 992:1045 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 3 6 theme naphthalene 749:759 arg1 core 761:764 naphthalene core 749:764 naphthalene core 749:764 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 6 7 theme C2 1312:1313 arg1 position 1315:1322 the C2 position 1308:1322 the C2 position 1308:1322 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 4 8 theme 14.2 nM 981:987 arg1 assay 1057:1061 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay 981:1061 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay 981:1061 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 3 9 theme core 761:764 arg1 position 722:729 C-2 position 718:729 C-2 position of the benzene or naphthalene core 718:764 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 4 10 theme 64.5 nM 926:932 arg1 IC50 918:921 an IC50 915:921 an IC50 of 64.5 nM 915:932 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 4 11 theme 2- 827:828 arg1 group 849:853 2-(4-fluorobenzyloxy) group 827:853 2-(4-fluorobenzyloxy) group 827:853 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 1 12 theme redox 295:299 arg1 homeostasis 301:311 the redox homeostasis 291:311 the redox homeostasis 291:311 The Keap1-Nrf2-ARE pathway plays an important role in responding to oxidative stress and maintaining the redox homeostasis. 35462166 0 13 theme acids 98:102 arg1 relationships 19:31 Structure-activity relationships 0:31 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 0:188 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 35462166 2 14 theme molecule 320:327 arg1 inhibitors 329:338 Small molecule inhibitors 314:338 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) 314:406 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 6 15 theme Keap1-Nrf2 1390:1399 arg1 inhibitors 1405:1414 Keap1-Nrf2 PPI inhibitors 1390:1414 Keap1-Nrf2 PPI inhibitors 1390:1414 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 5 16 theme mRNA 1146:1149 arg1 levels 1151:1156 the mRNA levels 1142:1156 the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1 1142:1204 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 4 17 theme Keap1-Nrf2 895:904 arg1 PPI 906:908 Keap1-Nrf2 PPI 895:908 Keap1-Nrf2 PPI 895:908 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 2 18 theme Small 314:318 arg1 inhibitors 329:338 Small molecule inhibitors 314:338 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) 314:406 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 1 19 theme Keap1-Nrf2-ARE 194:207 arg1 pathway 209:215 The Keap1-Nrf2-ARE pathway 190:215 The Keap1-Nrf2-ARE pathway 190:215 The Keap1-Nrf2-ARE pathway plays an important role in responding to oxidative stress and maintaining the redox homeostasis. 35462166 0 20 theme varying 109:115 arg1 C2-substituents 117:131 varying C2-substituents 109:131 varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction 109:187 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 35462166 6 21 theme O-linked 1286:1293 arg1 fragments 1295:1303 diverse O-linked fragments 1278:1303 diverse O-linked fragments 1278:1303 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 0 22 theme Structure-activity 0:17 arg1 relationships 19:31 Structure-activity relationships 0:31 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 0:188 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 35462166 2 23 theme effective 442:450 arg1 agents 479:484 effective preventive and therapeutic agents 442:484 effective preventive and therapeutic agents for numerous chronic inflammatory diseases 442:527 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 6 24 theme diverse 1278:1284 arg1 fragments 1295:1303 diverse O-linked fragments 1278:1303 diverse O-linked fragments 1278:1303 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 4 25 theme fluorescence 1008:1019 arg1 transfer 1038:1045 a time-resolved fluorescence resonance energy transfer 992:1045 a time-resolved fluorescence resonance energy transfer 992:1045 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 2 26 theme Keap1-Nrf2 363:372 arg1 PPI 403:405 PPI 403:405 PPI 403:405 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 2 26 theme Keap1-Nrf2 363:372 arg1 interaction 390:400 the Keap1-Nrf2 protein-protein interaction 359:400 the Keap1-Nrf2 protein-protein interaction (PPI) 359:406 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 2 27 theme inflammatory 507:518 arg1 diseases 520:527 numerous chronic inflammatory diseases 490:527 numerous chronic inflammatory diseases 490:527 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 4 28 theme PPI 906:908 arg1 12d 818:820 compound 12d 809:820 compound 12d with 2-(4-fluorobenzyloxy) group 809:853 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 4 28 theme PPI 906:908 arg1 inhibitor 882:890 the most potent direct inhibitor 859:890 the most potent direct inhibitor of Keap1-Nrf2 PPI 859:908 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 4 29 theme potent 868:873 arg1 12d 818:820 compound 12d 809:820 compound 12d with 2-(4-fluorobenzyloxy) group 809:853 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 4 29 theme potent 868:873 arg1 inhibitor 882:890 the most potent direct inhibitor 859:890 the most potent direct inhibitor of Keap1-Nrf2 PPI 859:908 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 6 30 contain possessing 1267:1276 arg2 fragments 1295:1303 diverse O-linked fragments 1278:1303 diverse O-linked fragments 1278:1303 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 6 30 contain possessing 1267:1276 arg1 scaffolds 1257:1265 the new scaffolds 1249:1265 the new scaffolds possessing diverse O-linked fragments at the C2 position 1249:1322 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 2 31 theme chronic 499:505 arg1 diseases 520:527 numerous chronic inflammatory diseases 490:527 numerous chronic inflammatory diseases 490:527 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 3 32 theme 1,4-bis 622:628 arg1 benzene 646:652 1,4-bis(arylsulfonamido)benzene 622:652 1,4-bis(arylsulfonamido)benzene 622:652 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 3 33 theme naphthalene-N 657:669 arg1 series 612:617 a series 610:617 a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core 610:764 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 1 34 theme important 226:234 arg1 role 236:239 an important role 223:239 an important role 223:239 The Keap1-Nrf2-ARE pathway plays an important role in responding to oxidative stress and maintaining the redox homeostasis. 35462166 2 35 theme numerous 490:497 arg1 diseases 520:527 numerous chronic inflammatory diseases 490:527 numerous chronic inflammatory diseases 490:527 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 6 36 theme chemical 1367:1374 arg1 structures 1376:1385 the chemical structures 1363:1385 the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles 1363:1477 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 3 37 theme C-2 718:720 arg1 position 722:729 C-2 position 718:729 C-2 position of the benzene or naphthalene core 718:764 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 4 38 theme compound 809:816 arg1 12d 818:820 compound 12d 809:820 compound 12d with 2-(4-fluorobenzyloxy) group 809:853 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 4 38 theme compound 809:816 arg1 inhibitor 882:890 the most potent direct inhibitor 859:890 the most potent direct inhibitor of Keap1-Nrf2 PPI 859:908 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 6 39 theme safety 1463:1468 arg1 profiles 1470:1477 safety profiles 1463:1477 safety profiles 1463:1477 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 5 40 theme Nrf2 1215:1218 arg1 activation 1220:1229 Nrf2 activation 1215:1229 Nrf2 activation 1215:1229 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 0 41 theme Keap1-Nrf2 150:159 arg1 interaction 177:187 Keap1-Nrf2 protein-protein interaction 150:187 Keap1-Nrf2 protein-protein interaction 150:187 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 35462166 0 42 dep -benzene 60:67 arg1 N'-diacetic 86:96 N'-diacetic 86:96 N'-diacetic 86:96 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 35462166 6 43 link O-linked 1286:1293 arg1 fragments 1295:1303 diverse O-linked fragments 1278:1303 diverse O-linked fragments 1278:1303 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 2 44 theme therapeutic 467:477 arg1 agents 479:484 effective preventive and therapeutic agents 442:484 effective preventive and therapeutic agents for numerous chronic inflammatory diseases 442:527 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 2 45 theme preventive 452:461 arg1 agents 479:484 effective preventive and therapeutic agents 442:484 effective preventive and therapeutic agents for numerous chronic inflammatory diseases 442:527 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 4 46 with 12d 818:820 arg1 group 849:853 2-(4-fluorobenzyloxy) group 827:853 2-(4-fluorobenzyloxy) group 827:853 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 6 47 theme new 1253:1255 arg1 scaffolds 1257:1265 the new scaffolds 1249:1265 the new scaffolds possessing diverse O-linked fragments at the C2 position 1249:1322 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 4 48 from inhibitor 882:890 arg1 assay 1057:1061 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay 981:1061 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay 981:1061 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 4 48 from inhibitor 882:890 arg1 assay 971:975 the fluorescent polarization (FP) assay 937:975 the fluorescent polarization (FP) assay 937:975 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 3 49 from position 722:729 arg1 substituents 702:713 varying substituents 694:713 varying substituents at C-2 position of the benzene or naphthalene core 694:764 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 0 50 theme -benzene 60:67 arg1 acids 98:102 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids 36:102 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids 36:102 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 35462166 6 51 theme inhibitors 1405:1414 arg1 structures 1376:1385 the chemical structures 1363:1385 the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles 1363:1477 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35462166 0 52 theme interaction 177:187 arg1 inhibitors 136:145 inhibitors 136:145 inhibitors of Keap1-Nrf2 protein-protein interaction 136:187 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 35462166 4 53 theme time-resolved 994:1006 arg1 transfer 1038:1045 a time-resolved fluorescence resonance energy transfer 992:1045 a time-resolved fluorescence resonance energy transfer 992:1045 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 3 54 theme benzene 646:652 arg1 series 612:617 a series 610:617 a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core 610:764 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 5 55 theme genes 1177:1181 arg1 levels 1151:1156 the mRNA levels 1142:1156 the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1 1142:1204 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 0 56 theme protein-protein 161:175 arg1 interaction 177:187 Keap1-Nrf2 protein-protein interaction 150:187 Keap1-Nrf2 protein-protein interaction 150:187 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 35462166 3 57 theme benzene 738:744 arg1 position 722:729 C-2 position 718:729 C-2 position of the benzene or naphthalene core 718:764 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 4 58 theme direct 875:880 arg1 12d 818:820 compound 12d 809:820 compound 12d with 2-(4-fluorobenzyloxy) group 809:853 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 4 58 theme direct 875:880 arg1 inhibitor 882:890 the most potent direct inhibitor 859:890 the most potent direct inhibitor of Keap1-Nrf2 PPI 859:908 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 0 59 with relationships 19:31 arg1 C2-substituents 117:131 varying C2-substituents 109:131 varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction 109:187 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 35462166 3 60 theme inhibitory 570:579 arg1 potency 581:587 inhibitory potency 570:587 inhibitory potency 570:587 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 5 61 theme cell-based 1074:1083 arg1 assay 1096:1100 cell-based biological assay 1074:1100 cell-based biological assay 1074:1100 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 3 62 theme arylsulfonamido 630:644 arg1 benzene 646:652 1,4-bis(arylsulfonamido)benzene 622:652 1,4-bis(arylsulfonamido)benzene 622:652 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 4 63 theme polarization 953:964 arg1 assay 971:975 the fluorescent polarization (FP) assay 937:975 the fluorescent polarization (FP) assay 937:975 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 5 64 theme biological 1085:1094 arg1 assay 1096:1100 cell-based biological assay 1074:1100 cell-based biological assay 1074:1100 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 4 65 from 14.2 nM 981:987 arg1 transfer 1038:1045 a time-resolved fluorescence resonance energy transfer 992:1045 a time-resolved fluorescence resonance energy transfer 992:1045 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 3 66 theme drug-like 545:553 arg1 properties 555:564 the drug-like properties 541:564 the drug-like properties 541:564 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 4 67 with inhibitor 882:890 arg1 IC50 918:921 an IC50 915:921 an IC50 of 64.5 nM 915:932 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 4 68 theme fluorescent 941:951 arg1 FP 967:968 FP 967:968 FP 967:968 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 4 68 theme fluorescent 941:951 arg1 polarization 953:964 the fluorescent polarization 937:964 the fluorescent polarization (FP) assay 937:975 Among them, compound 12d with 2-(4-fluorobenzyloxy) group was the most potent direct inhibitor of Keap1-Nrf2 PPI with an IC50 of 64.5 nM in the fluorescent polarization (FP) assay and 14.2 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. 35462166 3 69 theme varying 694:700 arg1 substituents 702:713 varying substituents 694:713 varying substituents at C-2 position of the benzene or naphthalene core 694:764 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 2 70 theme protein-protein 374:388 arg1 PPI 403:405 PPI 403:405 PPI 403:405 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 2 70 theme protein-protein 374:388 arg1 interaction 390:400 the Keap1-Nrf2 protein-protein interaction 359:400 the Keap1-Nrf2 protein-protein interaction (PPI) 359:406 Small molecule inhibitors targeting directly the Keap1-Nrf2 protein-protein interaction (PPI) can potentially be developed into effective preventive and therapeutic agents for numerous chronic inflammatory diseases. 35462166 1 71 theme oxidative 258:266 arg1 stress 268:273 oxidative stress 258:273 oxidative stress 258:273 The Keap1-Nrf2-ARE pathway plays an important role in responding to oxidative stress and maintaining the redox homeostasis. 35462166 0 72 theme naphthalene-N 72:84 arg1 acids 98:102 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids 36:102 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids 36:102 Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction. 35462166 3 73 theme N'-diacetic 671:681 arg1 naphthalene-N 657:669 naphthalene-N 657:669 naphthalene-N 657:669 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 3 73 theme N'-diacetic 671:681 arg1 acids 683:687 N'-diacetic acids 671:687 N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core 671:764 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 3 74 with acids 683:687 arg1 substituents 702:713 varying substituents 694:713 varying substituents at C-2 position of the benzene or naphthalene core 694:764 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 5 75 theme Nrf2 1161:1164 arg1 HMOX2 1191:1195 HMOX2 1191:1195 HMOX2 1191:1195 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 5 75 theme Nrf2 1161:1164 arg1 GSTM3 1184:1188 GSTM3 1184:1188 GSTM3 1184:1188 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 5 75 theme Nrf2 1161:1164 arg1 genes 1177:1181 Nrf2 downstream genes 1161:1181 Nrf2 downstream genes 1161:1181 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 5 75 theme Nrf2 1161:1164 arg1 NQO1 1201:1204 NQO1 1201:1204 NQO1 1201:1204 Moreover, cell-based biological assay showed that 12d significantly increased the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1, through Nrf2 activation. 35462166 3 76 theme inhibitors 598:607 arg1 properties 555:564 the drug-like properties 541:564 the drug-like properties 541:564 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 3 76 theme inhibitors 598:607 arg1 potency 581:587 inhibitory potency 570:587 inhibitory potency 570:587 To improve the drug-like properties and inhibitory potency of these inhibitors, a series of 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acids with varying substituents at C-2 position of the benzene or naphthalene core were designed and synthesized. 35462166 6 77 theme PPI 1401:1403 arg1 inhibitors 1405:1414 Keap1-Nrf2 PPI inhibitors 1390:1414 Keap1-Nrf2 PPI inhibitors 1390:1414 The discovery of the new scaffolds possessing diverse O-linked fragments at the C2 position offers opportunities to further modify the chemical structures of Keap1-Nrf2 PPI inhibitors to improve their pharmacokinetic, efficacy and safety profiles. 35278842 10 0 from similarity 1493:1502 arg1 transcriptome 1521:1533 the placental transcriptome 1507:1533 the placental transcriptome of women with obesity who do and do not have OSA during pregnancy 1507:1599 DISCUSSION There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. 35278842 9 1 from placentae 1345:1353 arg1 hydration 1310:1318 the reversible hydration 1295:1318 the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA 1295:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 7 2 dep glycosylation 1021:1033 arg1 pathways 1093:1100 pathways 1093:1100 pathways 1093:1100 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 7 2 dep glycosylation 1021:1033 arg1 B3GNT8 1047:1052 B3GNT8 1047:1052 B3GNT8 1047:1052 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 7 2 dep glycosylation 1021:1033 arg1 B3GNT5 1036:1041 B3GNT5 1036:1041 B3GNT5 1036:1041 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 1 3 theme increased 242:250 arg1 risk 252:255 an increased risk 239:255 an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy 239:356 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 11 4 from outcomes 1739:1746 arg1 OSA 1760:1762 maternal OSA 1751:1762 maternal OSA 1751:1762 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 10 5 with women 1538:1542 arg1 obesity 1549:1555 obesity 1549:1555 obesity 1549:1555 DISCUSSION There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. 35278842 7 6 link O-linked 1012:1019 arg1 glycosylation 1021:1033 O-linked glycosylation 1012:1033 O-linked glycosylation (B3GNT5 and B3GNT8) 1012:1053 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 8 7 theme set 1111:1113 arg1 analysis 1126:1133 gene set enrichment analysis 1106:1133 gene set enrichment analysis 1106:1133 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 10 8 contain have 1575:1578 arg2 OSA 1580:1582 OSA 1580:1582 OSA 1580:1582 DISCUSSION There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. 35278842 10 8 contain have 1575:1578 arg1 women 1538:1542 women 1538:1542 women with obesity who do and do not have OSA during pregnancy 1538:1599 DISCUSSION There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. 35278842 1 9 theme adverse 260:266 arg1 outcomes 278:285 adverse pregnancy outcomes 260:285 adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy 260:356 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 1 9 theme adverse 260:266 arg1 diabetes 309:316 gestational diabetes 297:316 gestational diabetes 297:316 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 1 9 theme adverse 260:266 arg1 disorders 335:343 hypertensive disorders 322:343 hypertensive disorders of pregnancy 322:356 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 8 10 theme non-random 1167:1176 arg1 distribution 1178:1189 a non-random distribution 1165:1189 a non-random distribution in OSA 1165:1196 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 7 11 dep signalling 1063:1072 arg1 FRZB 1087:1090 FRZB 1087:1090 FRZB 1087:1090 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 7 11 dep signalling 1063:1072 arg1 TRABD2B 1075:1081 TRABD2B 1075:1081 TRABD2B 1075:1081 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 10 12 dep DISCUSSION 1465:1474 arg1 There 1476:1480 There 1476:1480 There 1476:1480 DISCUSSION There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. 35278842 9 13 theme novel 1368:1372 arg1 mechanism 1374:1382 a potential novel mechanism 1356:1382 a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA 1356:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 9 13 theme novel 1368:1372 arg1 placentae 1345:1353 OSA placentae 1341:1353 OSA placentae 1341:1353 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 11 14 theme larger 1809:1814 arg1 cohorts 1816:1822 larger cohorts 1809:1822 larger cohorts 1809:1822 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 10 15 theme women 1538:1542 arg1 transcriptome 1521:1533 the placental transcriptome 1507:1533 the placental transcriptome of women with obesity who do and do not have OSA during pregnancy 1507:1599 DISCUSSION There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. 35278842 11 16 theme outcomes 1739:1746 arg1 development 1706:1716 the development 1702:1716 the development of adverse pregnancy outcomes in maternal OSA 1702:1762 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 9 17 theme carbon 1323:1328 arg1 dioxide 1330:1336 carbon dioxide 1323:1336 carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA 1323:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 4 18 with women 600:604 arg1 obesity 611:617 obesity 611:617 obesity 611:617 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 4 18 with women 600:604 arg1 n = 11 588:593 n = 11 588:593 n = 11 588:593 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 4 18 with women 600:604 arg1 OSA 626:628 no OSA 623:628 no OSA (n = 9) 623:636 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 4 18 with women 600:604 arg1 obesity 571:577 obesity 571:577 obesity 571:577 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 4 18 with women 600:604 arg1 n = 9 631:635 n = 9 631:635 n = 9 631:635 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 4 18 with women 600:604 arg1 OSA 583:585 OSA 583:585 OSA (n = 11) 583:594 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 11 19 theme adverse 1721:1727 arg1 outcomes 1739:1746 adverse pregnancy outcomes 1721:1746 adverse pregnancy outcomes in maternal OSA 1721:1762 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 7 20 theme genes 994:998 arg1 downregulation 976:989 downregulation 976:989 downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways 976:1100 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 7 21 theme term 947:950 arg1 analysis 952:959 GO term analysis 944:959 GO term analysis 944:959 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 11 22 theme dioxide 1652:1658 arg1 hydration 1632:1640 the reversible hydration 1617:1640 the reversible hydration of carbon dioxide 1617:1658 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 5 23 from differences 726:736 arg1 expression 746:755 gene expression 741:755 gene expression 741:755 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 8 24 theme adjusted 1228:1235 arg1 placentae 1217:1225 no OSA placentae 1210:1225 no OSA placentae (adjusted p < 0.05) 1210:1245 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 8 24 theme adjusted 1228:1235 arg1 p < 0.05 1237:1244 adjusted p < 0.05 1228:1244 adjusted p < 0.05 1228:1244 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 4 25 from women 600:604 arg1 placenta 546:553 placenta 546:553 placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9) 546:636 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 7 26 theme Reactome 923:930 arg1 pathway 932:938 Reactome pathway 923:938 Reactome pathway 923:938 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 9 27 theme pregnancy 1427:1435 arg1 outcomes 1437:1444 adverse pregnancy outcomes 1419:1444 adverse pregnancy outcomes in women with OSA 1419:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 0 28 theme obstructive 67:77 arg1 apnoea 85:90 obstructive sleep apnoea 67:90 obstructive sleep apnoea 67:90 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea. 35278842 1 29 theme pregnancy 348:356 arg1 diabetes 309:316 gestational diabetes 297:316 gestational diabetes 297:316 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 1 29 theme pregnancy 348:356 arg1 disorders 335:343 hypertensive disorders 322:343 hypertensive disorders of pregnancy 322:356 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 9 30 from women 1449:1453 arg1 development 1404:1414 the development 1400:1414 the development of adverse pregnancy outcomes in women with OSA 1400:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 5 31 dep RESULTS 639:645 arg1 were 692:695 were 692:695 were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05) 692:805 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 0 32 from women 44:48 arg1 profiling 16:24 Gene expression profiling 0:24 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea 0:90 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea. 35278842 11 33 from validation 1795:1804 arg1 cohorts 1816:1822 larger cohorts 1809:1822 larger cohorts 1809:1822 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 5 34 theme significant 714:724 arg1 differences 726:736 no statistically significant differences 697:736 no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05) 697:805 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 11 35 from OSA 1760:1762 arg1 development 1706:1716 the development 1702:1716 the development of adverse pregnancy outcomes in maternal OSA 1702:1762 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 2 36 theme associations 394:405 arg1 mechanisms 374:383 The biological mechanisms 359:383 The biological mechanisms of these associations 359:405 The biological mechanisms of these associations are poorly understood. 35278842 0 37 theme Gene 0:3 arg1 profiling 16:24 Gene expression profiling 0:24 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea 0:90 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea. 35278842 4 38 dep METHODS 503:509 arg1 performed 514:522 performed 514:522 performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9) 514:636 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 5 39 theme adjusted 788:795 arg1 groups 780:785 OSA and no OSA groups 765:785 groups 780:785 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 5 39 theme adjusted 788:795 arg1 p < 0.05 797:804 adjusted p < 0.05 788:804 adjusted p < 0.05 788:804 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 1 40 theme outcomes 278:285 arg1 risk 252:255 an increased risk 239:255 an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy 239:356 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 1 41 theme Obstructive 106:116 arg1 OSA 132:134 OSA 132:134 OSA 132:134 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 1 41 theme Obstructive 106:116 arg1 apnoea 124:129 Obstructive sleep apnoea 106:129 INTRODUCTION Obstructive sleep apnoea (OSA) 93:135 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 1 42 dep INTRODUCTION 93:104 arg1 OSA 132:134 OSA 132:134 OSA 132:134 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 1 42 dep INTRODUCTION 93:104 arg1 apnoea 124:129 Obstructive sleep apnoea 106:129 INTRODUCTION Obstructive sleep apnoea (OSA) 93:135 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 0 43 theme placentae 29:37 arg1 profiling 16:24 Gene expression profiling 0:24 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea 0:90 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea. 35278842 1 44 theme gestational 297:307 arg1 diabetes 309:316 gestational diabetes 297:316 gestational diabetes 297:316 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 5 45 theme OSA 765:767 arg1 groups 780:785 OSA and no OSA groups 765:785 groups 780:785 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 5 45 theme OSA 765:767 arg1 p < 0.05 797:804 adjusted p < 0.05 788:804 adjusted p < 0.05 788:804 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 4 46 theme mRNA 527:530 arg1 sequencing 532:541 3' mRNA sequencing 524:541 3' mRNA sequencing 524:541 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 5 47 theme no 773:774 arg1 groups 780:785 OSA and no OSA groups 765:785 groups 780:785 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 5 47 theme no 773:774 arg1 p < 0.05 797:804 adjusted p < 0.05 788:804 adjusted p < 0.05 788:804 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 9 48 from hydration 1310:1318 arg1 mechanism 1374:1382 a potential novel mechanism 1356:1382 a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA 1356:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 9 48 from hydration 1310:1318 arg1 placentae 1345:1353 OSA placentae 1341:1353 OSA placentae 1341:1353 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 11 49 theme maternal 1751:1758 arg1 OSA 1760:1762 maternal OSA 1751:1762 maternal OSA 1751:1762 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 0 50 with women 44:48 arg1 obesity 55:61 obesity 55:61 obesity 55:61 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea. 35278842 0 50 with women 44:48 arg1 apnoea 85:90 obstructive sleep apnoea 67:90 obstructive sleep apnoea 67:90 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea. 35278842 9 51 theme reversible 1299:1308 arg1 hydration 1310:1318 the reversible hydration 1295:1318 the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA 1295:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 5 52 theme gene 741:744 arg1 expression 746:755 gene expression 741:755 gene expression 741:755 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 7 53 theme Wnt 1059:1061 arg1 signalling 1063:1072 Wnt signalling 1059:1072 Wnt signalling (TRABD2B and FRZB) 1059:1091 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 2 54 theme biological 363:372 arg1 mechanisms 374:383 The biological mechanisms 359:383 The biological mechanisms of these associations 359:405 The biological mechanisms of these associations are poorly understood. 35278842 11 55 from development 1706:1716 arg1 OSA 1760:1762 maternal OSA 1751:1762 maternal OSA 1751:1762 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 9 56 from outcomes 1437:1444 arg1 women 1449:1453 women 1449:1453 women with OSA 1449:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 10 57 theme overall 1485:1491 arg1 similarity 1493:1502 overall similarity 1485:1502 overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy 1485:1599 DISCUSSION There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. 35278842 9 58 theme dioxide 1330:1336 arg1 hydration 1310:1318 the reversible hydration 1295:1318 the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA 1295:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 4 59 with women 560:564 arg1 obesity 611:617 obesity 611:617 obesity 611:617 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 4 59 with women 560:564 arg1 n = 11 588:593 n = 11 588:593 n = 11 588:593 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 4 59 with women 560:564 arg1 OSA 626:628 no OSA 623:628 no OSA (n = 9) 623:636 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 4 59 with women 560:564 arg1 obesity 571:577 obesity 571:577 obesity 571:577 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 4 59 with women 560:564 arg1 n = 9 631:635 n = 9 631:635 n = 9 631:635 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 4 59 with women 560:564 arg1 OSA 583:585 OSA 583:585 OSA (n = 11) 583:594 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 9 60 theme OSA 1341:1343 arg1 mechanism 1374:1382 a potential novel mechanism 1356:1382 a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA 1356:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 9 60 theme OSA 1341:1343 arg1 placentae 1345:1353 OSA placentae 1341:1353 OSA placentae 1341:1353 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 9 61 from development 1404:1414 arg1 women 1449:1453 women 1449:1453 women with OSA 1449:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 10 62 theme placental 1511:1519 arg1 transcriptome 1521:1533 the placental transcriptome 1507:1533 the placental transcriptome of women with obesity who do and do not have OSA during pregnancy 1507:1599 DISCUSSION There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. 35278842 1 63 theme intermittent 167:178 arg1 hypoxia 180:186 intermittent hypoxia 167:186 intermittent hypoxia 167:186 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 8 64 theme gene 1106:1109 arg1 analysis 1126:1133 gene set enrichment analysis 1106:1133 gene set enrichment analysis 1106:1133 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 8 65 contain had 1161:1163 arg1 genes 1136:1140 genes 1136:1140 genes within 24 pathways 1136:1159 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 8 65 contain had 1161:1163 arg2 distribution 1178:1189 a non-random distribution 1165:1189 a non-random distribution in OSA 1165:1196 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 7 66 theme O-linked 1012:1019 arg1 glycosylation 1021:1033 O-linked glycosylation 1012:1033 O-linked glycosylation (B3GNT5 and B3GNT8) 1012:1053 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 9 67 theme potential 1358:1366 arg1 mechanism 1374:1382 a potential novel mechanism 1356:1382 a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA 1356:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 9 67 theme potential 1358:1366 arg1 placentae 1345:1353 OSA placentae 1341:1353 OSA placentae 1341:1353 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 8 68 theme enrichment 1115:1124 arg1 analysis 1126:1133 gene set enrichment analysis 1106:1133 gene set enrichment analysis 1106:1133 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 9 69 with women 1449:1453 arg1 OSA 1460:1462 OSA 1460:1462 OSA 1460:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 1 70 theme sleep 118:122 arg1 OSA 132:134 OSA 132:134 OSA 132:134 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 1 70 theme sleep 118:122 arg1 apnoea 124:129 Obstructive sleep apnoea 106:129 INTRODUCTION Obstructive sleep apnoea (OSA) 93:135 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 6 71 theme OSA 894:896 arg1 placentae 898:906 no OSA placentae 891:906 no OSA placentae (p < 0.01) 891:917 In unadjusted analyses, 101 genes were differentially expressed in OSA compared to no OSA placentae (p < 0.01). 35278842 6 71 theme OSA 894:896 arg1 p < 0.01 909:916 p < 0.01 909:916 p < 0.01 909:916 In unadjusted analyses, 101 genes were differentially expressed in OSA compared to no OSA placentae (p < 0.01). 35278842 5 72 theme multiple 668:675 arg1 testing 677:683 multiple testing 668:683 multiple testing 668:683 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 11 73 theme pregnancy 1729:1737 arg1 outcomes 1739:1746 adverse pregnancy outcomes 1721:1746 adverse pregnancy outcomes in maternal OSA 1721:1762 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 8 74 theme OSA 1213:1215 arg1 placentae 1217:1225 no OSA placentae 1210:1225 no OSA placentae (adjusted p < 0.05) 1210:1245 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 8 74 theme OSA 1213:1215 arg1 p < 0.05 1237:1244 adjusted p < 0.05 1228:1244 adjusted p < 0.05 1228:1244 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 7 75 theme GO 944:945 arg1 analysis 952:959 GO term analysis 944:959 GO term analysis 944:959 In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. 35278842 9 76 theme adverse 1419:1425 arg1 outcomes 1437:1444 adverse pregnancy outcomes 1419:1444 adverse pregnancy outcomes in women with OSA 1419:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 11 77 theme carbon 1645:1650 arg1 dioxide 1652:1658 carbon dioxide 1645:1658 carbon dioxide 1645:1658 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 0 78 theme sleep 79:83 arg1 apnoea 85:90 obstructive sleep apnoea 67:90 obstructive sleep apnoea 67:90 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea. 35278842 8 79 from distribution 1178:1189 arg1 OSA 1194:1196 OSA 1194:1196 OSA 1194:1196 In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). 35278842 9 80 theme outcomes 1437:1444 arg1 development 1404:1414 the development 1400:1414 the development of adverse pregnancy outcomes in women with OSA 1400:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 3 81 from impact 434:439 arg1 function 461:468 placental function 451:468 placental function 451:468 The impact of OSA on placental function has not been well characterised. 35278842 9 82 from increase 1265:1272 arg1 genes 1277:1281 genes 1277:1281 genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA 1277:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 11 83 theme potential 1666:1674 arg1 Alterations 1602:1612 Alterations 1602:1612 Alterations in the reversible hydration of carbon dioxide 1602:1658 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 11 83 theme potential 1666:1674 arg1 mechanism 1676:1684 a potential mechanism 1664:1684 a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA 1664:1762 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 11 84 from Alterations 1602:1612 arg1 hydration 1632:1640 the reversible hydration 1617:1640 the reversible hydration of carbon dioxide 1617:1658 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 3 85 theme placental 451:459 arg1 function 461:468 placental function 451:468 placental function 451:468 The impact of OSA on placental function has not been well characterised. 35278842 0 86 theme expression 5:14 arg1 profiling 16:24 Gene expression profiling 0:24 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea 0:90 Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea. 35278842 3 87 theme OSA 444:446 arg1 impact 434:439 The impact 430:439 The impact of OSA on placental function 430:468 The impact of OSA on placental function has not been well characterised. 35278842 4 88 from women 560:564 arg1 placenta 546:553 placenta 546:553 placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9) 546:636 METHODS We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). 35278842 1 89 theme pregnancy 268:276 arg1 outcomes 278:285 adverse pregnancy outcomes 260:285 adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy 260:356 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 1 89 theme pregnancy 268:276 arg1 diabetes 309:316 gestational diabetes 297:316 gestational diabetes 297:316 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 1 89 theme pregnancy 268:276 arg1 disorders 335:343 hypertensive disorders 322:343 hypertensive disorders of pregnancy 322:356 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 9 90 from dioxide 1330:1336 arg1 mechanism 1374:1382 a potential novel mechanism 1356:1382 a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA 1356:1462 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 9 90 from dioxide 1330:1336 arg1 placentae 1345:1353 OSA placentae 1341:1353 OSA placentae 1341:1353 This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. 35278842 6 91 theme unadjusted 811:820 arg1 analyses 822:829 unadjusted analyses 811:829 unadjusted analyses 811:829 In unadjusted analyses, 101 genes were differentially expressed in OSA compared to no OSA placentae (p < 0.01). 35278842 11 92 theme reversible 1621:1630 arg1 hydration 1632:1640 the reversible hydration 1617:1640 the reversible hydration of carbon dioxide 1617:1658 Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts. 35278842 1 93 theme hypertensive 322:333 arg1 disorders 335:343 hypertensive disorders 322:343 hypertensive disorders of pregnancy 322:356 INTRODUCTION Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. 35278842 5 94 theme OSA 776:778 arg1 groups 780:785 OSA and no OSA groups 765:785 groups 780:785 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 35278842 5 94 theme OSA 776:778 arg1 p < 0.05 797:804 adjusted p < 0.05 788:804 adjusted p < 0.05 788:804 RESULTS After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). 37031439 7 0 theme molecular 1233:1241 arg1 analyses 1243:1250 biochemical and molecular analyses 1217:1250 biochemical and molecular analyses 1217:1250 Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. 37031439 7 1 theme emotional 1113:1121 arg1 reactivity 1123:1132 emotional reactivity 1113:1132 emotional reactivity 1113:1132 Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. 37031439 3 2 theme Impaired 502:509 arg1 metabolism 519:528 Impaired glucose metabolism 502:528 Impaired glucose metabolism 502:528 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 10 3 from expression 1668:1677 arg1 dorsal 1705:1710 hippocampal-associated dorsal 1682:1710 hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice 1682:1772 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 9 4 theme agouti 1438:1443 arg1 KKAy+/- 1445:1451 agouti KKAy+/- 1438:1451 agouti KKAy+/- 1438:1451 Behaviorally, agouti KKAy+/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy-/- mice. 37031439 7 5 theme sensorimotor 1086:1097 arg1 function 1099:1106 sensorimotor function 1086:1106 sensorimotor function 1086:1106 Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. 37031439 3 6 theme glucose 538:544 arg1 flux 546:549 glucose flux 538:549 glucose flux 538:549 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 5 7 theme C57BL/6 866:872 arg1 non-agouti 875:884 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice 850:918 non-agouti 875:884 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. 37031439 8 8 theme Body 1253:1256 arg1 weight 1258:1263 Body weight 1253:1263 Body weight 1253:1263 Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . 37031439 6 9 theme Body 966:969 arg1 weight 971:976 Body weight 966:976 Body weight 966:976 Body weight, blood glucose, total cholesterol, and triglyceride were measured to confirm the MetS phenotype. 37031439 10 10 theme O-GlcNAc 1651:1658 arg1 expression 1668:1677 reduced O-GlcNAc protein expression 1643:1677 reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice 1643:1772 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 11 11 theme O-GlcNAc 1894:1901 arg1 signaling 1903:1911 reduced O-GlcNAc signaling 1886:1911 reduced O-GlcNAc signaling in aging MetS KKAy+/- mice 1886:1938 Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. 37031439 3 12 theme hexosamine 563:572 arg1 pathway 584:590 the hexosamine metabolic pathway 559:590 the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification 559:673 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 12 13 theme cognitive 2058:2066 arg1 dysfunction 2068:2078 MetS-induced cognitive dysfunction 2045:2078 MetS-induced cognitive dysfunction in aging 2045:2087 Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging. 37031439 10 14 theme midbrain 1712:1719 arg1 dorsal 1705:1710 hippocampal-associated dorsal 1682:1710 hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice 1682:1772 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 0 15 theme metabolic 129:137 arg1 syndrome 139:146 metabolic syndrome 129:146 metabolic syndrome 129:146 Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome. 37031439 3 16 theme N-acetylglucosamine 623:641 arg1 modification 662:673 attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification 603:673 attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification 603:673 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 8 17 theme total 1281:1285 arg1 cholesterol 1287:1297 total cholesterol 1281:1297 total cholesterol 1281:1297 Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . 37031439 10 18 theme hippocampal-associated 1682:1703 arg1 dorsal 1705:1710 hippocampal-associated dorsal 1682:1710 hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice 1682:1772 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 11 19 theme MetS 1922:1925 arg1 mice 1935:1938 aging MetS KKAy+/- mice 1916:1938 aging MetS KKAy+/- mice 1916:1938 Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. 37031439 3 20 theme attenuated 603:612 arg1 modification 662:673 attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification 603:673 attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification 603:673 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 9 21 theme age-matched 1520:1530 arg1 C57BL/6 1532:1538 age-matched C57BL/6 and non-agouti KKAy-/- mice 1520:1566 C57BL/6 1532:1538 Behaviorally, agouti KKAy+/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy-/- mice. 37031439 11 22 theme AD-related 1845:1854 arg1 pathology 1856:1864 AD-related pathology 1845:1864 AD-related pathology 1845:1864 Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. 37031439 3 23 theme protein 654:660 arg1 modification 662:673 attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification 603:673 attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification 603:673 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 5 24 theme aged 925:928 arg1 12-18 months 930:941 aged 12-18 months 925:941 aged 12-18 months on standard chow diet 925:963 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. 37031439 8 25 theme triglyceride 1304:1315 arg1 levels 1317:1322 triglyceride levels 1304:1322 triglyceride levels 1304:1322 Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . 37031439 9 26 theme KKAy-/- 1555:1561 arg1 mice 1563:1566 age-matched C57BL/6 and non-agouti KKAy-/- mice 1520:1566 mice 1563:1566 Behaviorally, agouti KKAy+/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy-/- mice. 37031439 6 27 theme total 994:998 arg1 cholesterol 1000:1010 total cholesterol 994:1010 total cholesterol 994:1010 Body weight, blood glucose, total cholesterol, and triglyceride were measured to confirm the MetS phenotype. 37031439 2 28 theme cerebral 469:476 arg1 hypometabolism 486:499 cerebral glucose hypometabolism 469:499 cerebral glucose hypometabolism 469:499 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 0 29 theme O-GlcNAc 83:90 arg1 signaling 92:100 reduced O-GlcNAc signaling 75:100 reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome 75:146 Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome. 37031439 5 30 theme agouti 900:905 arg1 mice 915:918 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice 850:918 mice 915:918 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. 37031439 4 31 theme O-GlcNAc 781:788 arg1 signaling 790:798 O-GlcNAc signaling 781:798 O-GlcNAc signaling 781:798 The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . 37031439 7 32 theme tissue 1195:1200 arg1 collection 1202:1211 plasma and brain tissue collection 1178:1211 plasma and brain tissue collection for biochemical and molecular analyses 1178:1250 Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. 37031439 8 33 theme agouti 1355:1360 arg1 mice 1370:1373 agouti KKAy+/- mice 1355:1373 agouti KKAy+/- mice 1355:1373 Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . 37031439 0 34 theme aging 108:112 arg1 model 120:124 an aging mouse model 105:124 an aging mouse model of metabolic syndrome 105:146 Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome. 37031439 12 35 theme tau 1989:1991 arg1 pathology 1993:2001 tau pathology 1989:2001 tau pathology 1989:2001 Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging. 37031439 6 36 theme MetS 1059:1062 arg1 phenotype 1064:1072 the MetS phenotype 1055:1072 the MetS phenotype 1055:1072 Body weight, blood glucose, total cholesterol, and triglyceride were measured to confirm the MetS phenotype. 37031439 0 37 theme reduced 75:81 arg1 signaling 92:100 reduced O-GlcNAc signaling 75:100 reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome 75:146 Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome. 37031439 4 38 theme tau 762:764 arg1 pathology 766:774 tau pathology 762:774 tau pathology 762:774 The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . 37031439 2 39 theme hyperphosphorylated 370:388 arg1 tau 390:392 hyperphosphorylated tau 370:392 hyperphosphorylated tau 370:392 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 2 39 theme hyperphosphorylated 370:388 arg1 component 397:405 a component 395:405 a component of Alzheimer's disease-related dementia (ADRD) pathology 395:462 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 0 40 theme Cognitive 0:8 arg1 dysfunction 10:20 Cognitive dysfunction 0:20 Cognitive dysfunction 0:20 Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome. 37031439 2 41 theme disease-related 422:436 arg1 pathology 454:462 Alzheimer's disease-related dementia (ADRD) pathology 410:462 Alzheimer's disease-related dementia (ADRD) pathology 410:462 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 8 42 theme C57BL/6 1382:1388 arg1 controls 1390:1397 C57BL/6 controls 1382:1397 C57BL/6 controls 1382:1397 Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . 37031439 5 43 theme chow 955:958 arg1 diet 960:963 standard chow diet 946:963 standard chow diet 946:963 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. 37031439 9 44 theme non-agouti 1544:1553 arg1 mice 1563:1566 age-matched C57BL/6 and non-agouti KKAy-/- mice 1520:1566 mice 1563:1566 Behaviorally, agouti KKAy+/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy-/- mice. 37031439 4 45 theme MetS 827:830 arg1 model 818:822 an aging mouse model 803:822 an aging mouse model of MetS, agouti KKAy+/- 803:846 The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . 37031439 10 46 theme control 1761:1767 arg1 mice 1769:1772 female agouti KKAy+/- versus C57BL/6 control mice 1724:1772 mice 1769:1772 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 0 47 theme phosphorylated 36:49 arg1 tau 51:53 increased phosphorylated tau 26:53 increased phosphorylated tau 26:53 Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome. 37031439 3 48 link O-linked 614:621 arg1 O-GlcNAc 644:651 O-GlcNAc 644:651 O-GlcNAc 644:651 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 3 48 link O-linked 614:621 arg1 N-acetylglucosamine 623:641 O-linked N-acetylglucosamine 614:641 attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification 603:673 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 11 49 from signaling 1903:1911 arg1 mice 1935:1938 aging MetS KKAy+/- mice 1916:1938 aging MetS KKAy+/- mice 1916:1938 Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. 37031439 11 50 theme cognitive 1822:1830 arg1 function 1832:1839 impaired cognitive function 1813:1839 impaired cognitive function 1813:1839 Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. 37031439 4 51 theme aging 806:810 arg1 model 818:822 an aging mouse model 803:822 an aging mouse model of MetS, agouti KKAy+/- 803:846 The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . 37031439 9 52 from impairments 1462:1472 arg1 sensorimotor 1477:1488 sensorimotor 1477:1488 sensorimotor 1477:1488 Behaviorally, agouti KKAy+/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy-/- mice. 37031439 9 52 from impairments 1462:1472 arg1 function 1504:1511 cognitive function 1494:1511 cognitive function 1494:1511 Behaviorally, agouti KKAy+/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy-/- mice. 37031439 1 53 theme Metabolic 149:157 arg1 MetS 169:172 MetS 169:172 MetS 169:172 Metabolic syndrome (MetS), characterized by hyperglycemia, obesity, and hyperlipidemia, can increase the risk of developing late-onset dementia. 37031439 1 53 theme Metabolic 149:157 arg1 syndrome 159:166 Metabolic syndrome 149:166 Metabolic syndrome (MetS) 149:173 Metabolic syndrome (MetS), characterized by hyperglycemia, obesity, and hyperlipidemia, can increase the risk of developing late-onset dementia. 37031439 10 54 theme phosphorylated 1607:1620 arg1 tau 1622:1624 increased phosphorylated tau 1597:1624 increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice 1597:1772 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 3 55 theme glucose 511:517 arg1 metabolism 519:528 Impaired glucose metabolism 502:528 Impaired glucose metabolism 502:528 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 7 56 theme plasma 1178:1183 arg1 collection 1202:1211 plasma and brain tissue collection 1178:1211 plasma and brain tissue collection for biochemical and molecular analyses 1178:1250 Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. 37031439 10 57 theme reduced 1643:1649 arg1 expression 1668:1677 reduced O-GlcNAc protein expression 1643:1677 reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice 1643:1772 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 4 58 theme study 700:704 arg1 goal 680:683 The goal 676:683 The goal of the current study 676:704 The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . 37031439 5 59 theme female 859:864 arg1 non-agouti 875:884 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice 850:918 non-agouti 875:884 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. 37031439 4 60 theme KKAy+/- 840:846 arg1 MetS 827:830 MetS 827:830 MetS 827:830 The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . 37031439 3 61 theme metabolic 574:582 arg1 pathway 584:590 the hexosamine metabolic pathway 559:590 the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification 559:673 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 4 62 theme current 692:698 arg1 study 700:704 the current study 688:704 the current study 688:704 The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . 37031439 10 63 theme protein 1660:1666 arg1 expression 1668:1677 reduced O-GlcNAc protein expression 1643:1677 reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice 1643:1772 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 11 64 theme aging 1916:1920 arg1 mice 1935:1938 aging MetS KKAy+/- mice 1916:1938 aging MetS KKAy+/- mice 1916:1938 Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. 37031439 2 65 theme Recent 294:299 arg1 studies 301:307 Recent studies 294:307 Recent studies in patients and mouse models 294:336 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 0 66 from signaling 92:100 arg1 model 120:124 an aging mouse model 105:124 an aging mouse model of metabolic syndrome 105:146 Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome. 37031439 0 67 theme syndrome 139:146 arg1 model 120:124 an aging mouse model 105:124 an aging mouse model of metabolic syndrome 105:146 Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome. 37031439 3 68 theme O-linked 614:621 arg1 O-GlcNAc 644:651 O-GlcNAc 644:651 O-GlcNAc 644:651 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 3 68 theme O-linked 614:621 arg1 N-acetylglucosamine 623:641 O-linked N-acetylglucosamine 614:641 attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification 603:673 Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. 37031439 9 69 theme cognitive 1494:1502 arg1 function 1504:1511 cognitive function 1494:1511 cognitive function 1494:1511 Behaviorally, agouti KKAy+/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy-/- mice. 37031439 12 70 theme MetS-induced 2045:2056 arg1 dysfunction 2068:2078 MetS-induced cognitive dysfunction 2045:2078 MetS-induced cognitive dysfunction in aging 2045:2087 Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging. 37031439 8 71 theme blood 1266:1270 arg1 glucose 1272:1278 blood glucose 1266:1278 blood glucose 1266:1278 Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . 37031439 5 72 theme KKAy+/- 907:913 arg1 mice 915:918 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice 850:918 mice 915:918 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. 37031439 11 73 theme KKAy+/- 1927:1933 arg1 mice 1935:1938 aging MetS KKAy+/- mice 1916:1938 aging MetS KKAy+/- mice 1916:1938 Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. 37031439 4 74 theme cognitive 742:750 arg1 function 752:759 cognitive function 742:759 cognitive function 742:759 The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . 37031439 7 75 theme biochemical 1217:1227 arg1 analyses 1243:1250 biochemical and molecular analyses 1217:1250 biochemical and molecular analyses 1217:1250 Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. 37031439 5 76 theme KKAy-/- 886:892 arg1 non-agouti 875:884 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice 850:918 non-agouti 875:884 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. 37031439 2 77 theme glucose 478:484 arg1 hypometabolism 486:499 cerebral glucose hypometabolism 469:499 cerebral glucose hypometabolism 469:499 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 11 78 theme reduced 1886:1892 arg1 signaling 1903:1911 reduced O-GlcNAc signaling 1886:1911 reduced O-GlcNAc signaling in aging MetS KKAy+/- mice 1886:1938 Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. 37031439 7 79 theme brain 1189:1193 arg1 tissue 1195:1200 brain tissue 1189:1200 brain tissue 1189:1200 Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. 37031439 2 80 from studies 301:307 arg1 patients 312:319 patients 312:319 patients 312:319 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 2 80 from studies 301:307 arg1 models 331:336 mouse models 325:336 mouse models 325:336 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 6 81 theme blood 979:983 arg1 glucose 985:991 blood glucose 979:991 blood glucose 979:991 Body weight, blood glucose, total cholesterol, and triglyceride were measured to confirm the MetS phenotype. 37031439 0 82 theme mouse 114:118 arg1 model 120:124 an aging mouse model 105:124 an aging mouse model of metabolic syndrome 105:146 Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome. 37031439 12 83 theme pathology 1993:2001 arg1 interaction 1974:1984 interaction 1974:1984 interaction of tau pathology with O-GlcNAc signaling 1974:2025 Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging. 37031439 10 84 theme KKAy+/- 1738:1744 arg1 midbrain 1712:1719 midbrain 1712:1719 midbrain 1712:1719 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 12 85 theme O-GlcNAc 2008:2015 arg1 signaling 2017:2025 O-GlcNAc signaling 2008:2025 O-GlcNAc signaling 2008:2025 Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging. 37031439 2 86 theme dementia 438:445 arg1 pathology 454:462 Alzheimer's disease-related dementia (ADRD) pathology 410:462 Alzheimer's disease-related dementia (ADRD) pathology 410:462 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 8 87 theme KKAy+/- 1362:1368 arg1 mice 1370:1373 agouti KKAy+/- mice 1355:1373 agouti KKAy+/- mice 1355:1373 Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . 37031439 0 88 theme increased 26:34 arg1 tau 51:53 increased phosphorylated tau 26:53 increased phosphorylated tau 26:53 Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome. 37031439 5 89 theme standard 946:953 arg1 diet 960:963 standard chow diet 946:963 standard chow diet 946:963 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. 37031439 10 90 theme mice 1769:1772 arg1 midbrain 1712:1719 midbrain 1712:1719 midbrain 1712:1719 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 5 91 theme Male 850:853 arg1 non-agouti 875:884 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice 850:918 non-agouti 875:884 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. 37031439 2 92 theme pathology 454:462 arg1 tau 390:392 hyperphosphorylated tau 370:392 hyperphosphorylated tau 370:392 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 2 92 theme pathology 454:462 arg1 component 397:405 a component 395:405 a component of Alzheimer's disease-related dementia (ADRD) pathology 395:462 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 10 93 theme C57BL/6 1753:1759 arg1 mice 1769:1772 female agouti KKAy+/- versus C57BL/6 control mice 1724:1772 mice 1769:1772 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 2 94 theme ADRD 448:451 arg1 pathology 454:462 Alzheimer's disease-related dementia (ADRD) pathology 410:462 Alzheimer's disease-related dementia (ADRD) pathology 410:462 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 11 95 theme impaired 1813:1820 arg1 function 1832:1839 impaired cognitive function 1813:1839 impaired cognitive function 1813:1839 Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. 37031439 8 96 theme non-agouti 1403:1412 arg1 KKAy-/- 1414:1420 non-agouti KKAy-/- 1403:1420 non-agouti KKAy-/- 1403:1420 Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . 37031439 2 97 theme mouse 325:329 arg1 models 331:336 mouse models 325:336 mouse models 325:336 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 37031439 12 98 from dysfunction 2068:2078 arg1 aging 2083:2087 aging 2083:2087 aging 2083:2087 Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging. 37031439 5 99 from 12-18 months 930:941 arg1 diet 960:963 standard chow diet 946:963 standard chow diet 946:963 Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. 37031439 12 100 with interaction 1974:1984 arg1 signaling 2017:2025 O-GlcNAc signaling 2008:2025 O-GlcNAc signaling 2008:2025 Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging. 37031439 10 101 theme increased 1597:1605 arg1 tau 1622:1624 increased phosphorylated tau 1597:1624 increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice 1597:1772 Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. 37031439 4 102 theme mouse 812:816 arg1 model 818:822 an aging mouse model 803:822 an aging mouse model of MetS, agouti KKAy+/- 803:846 The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . 37031439 2 103 theme putative 348:355 arg1 link 357:360 a putative link 346:360 a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism 346:499 Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. 36565645 7 0 theme N-acetylglucosamine 1142:1160 arg1 modification 1173:1184 O-linked N-acetylglucosamine (O-GlcNAc) modification 1133:1184 O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD 1133:1192 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 8 1 theme central 1488:1494 arg1 enhancement 1602:1612 the enhancement 1598:1612 the enhancement of G6PD glycosylation 1598:1634 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 8 1 theme central 1488:1494 arg1 mechanisms 1496:1505 the central mechanisms 1484:1505 the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier 1484:1592 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 2 2 theme mucus 321:325 arg1 synthesis 327:335 mucus synthesis 321:335 mucus synthesis 321:335 Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. 36565645 7 3 theme burn 1436:1439 arg1 sepsis 1441:1446 burn sepsis 1436:1446 burn sepsis 1436:1446 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 1 4 theme first 161:165 arg1 line 167:170 the first line 157:170 the first line of defence of the intestinal mucosa barrier 157:214 Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. 36565645 1 5 theme core 234:237 arg1 component 239:247 its core component 230:247 its core component 230:247 Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. 36565645 0 6 theme mucus 108:112 arg1 barrier 114:120 the intestinal mucus barrier 93:120 the intestinal mucus barrier in burned septic mice 93:142 Glutamine promotes O-GlcNAcylation of G6PD and inhibits AGR2 S-glutathionylation to maintain the intestinal mucus barrier in burned septic mice. 36565645 3 7 theme burn 626:629 arg1 sepsis 631:636 burn sepsis 626:636 burn sepsis 626:636 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 2 8 theme vital 265:269 arg1 substance 278:286 a vital energy substance 263:286 a vital energy substance for goblet cells 263:303 Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. 36565645 2 8 theme vital 265:269 arg1 Glutamine 250:258 Glutamine 250:258 Glutamine 250:258 Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. 36565645 2 9 theme goblet 292:297 arg1 cells 299:303 goblet cells 292:303 goblet cells 292:303 Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. 36565645 0 10 theme intestinal 97:106 arg1 barrier 114:120 the intestinal mucus barrier 93:120 the intestinal mucus barrier in burned septic mice 93:142 Glutamine promotes O-GlcNAcylation of G6PD and inhibits AGR2 S-glutathionylation to maintain the intestinal mucus barrier in burned septic mice. 36565645 8 11 theme glycosylation 1622:1634 arg1 inhibition 1640:1649 inhibition 1640:1649 inhibition of AGR2 S-glutathionylation 1640:1677 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 8 11 theme glycosylation 1622:1634 arg1 enhancement 1602:1612 the enhancement 1598:1612 the enhancement of G6PD glycosylation 1598:1634 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 8 11 theme glycosylation 1622:1634 arg1 mechanisms 1496:1505 the central mechanisms 1484:1505 the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier 1484:1592 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 6 12 theme AGR2 1099:1102 arg1 activity 1104:1111 AGR2 activity 1099:1111 AGR2 activity 1099:1111 Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. 36565645 7 13 theme G6PD 1189:1192 arg1 modification 1173:1184 O-linked N-acetylglucosamine (O-GlcNAc) modification 1133:1184 O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD 1133:1192 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 7 14 theme homodimer 1245:1253 arg1 formation 1255:1263 G6PD homodimer formation 1240:1263 G6PD homodimer formation 1240:1263 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 3 15 theme molecular 478:486 arg1 mechanisms 488:497 the molecular mechanisms 474:497 the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis 474:636 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 7 16 theme intestinal 1405:1414 arg1 barrier 1422:1428 the intestinal mucus barrier 1401:1428 the intestinal mucus barrier 1401:1428 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 4 17 theme key 688:690 arg1 role 692:695 a key role 686:695 a key role 686:695 We found that anterior gradient-2 (AGR2) plays a key role in the posttranslational modification of MUC2. 36565645 3 18 dep synthesis 542:550 arg1 the 538:540 the 538:540 the 538:540 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 7 19 theme mucus 1416:1420 arg1 barrier 1422:1428 the intestinal mucus barrier 1401:1428 the intestinal mucus barrier 1401:1428 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 7 20 mod modification 1173:1184 arg1 G6PD 1189:1192 G6PD 1189:1192 G6PD 1189:1192 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 7 20 mod modification 1173:1184 arg3 N-acetylglucosamine 1142:1160 O-linked N-acetylglucosamine 1133:1160 O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD 1133:1192 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 7 20 mod modification 1173:1184 arg3 O-GlcNAc 1163:1170 O-GlcNAc 1163:1170 O-GlcNAc 1163:1170 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 3 21 theme glutamine 525:533 arg1 effects 514:520 the effects 510:520 the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) 510:585 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 8 22 theme mucus 1580:1584 arg1 barrier 1586:1592 the intestinal mucus barrier 1565:1592 the intestinal mucus barrier 1565:1592 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 1 23 theme defence 175:181 arg1 line 167:170 the first line 157:170 the first line of defence of the intestinal mucosa barrier 157:214 Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. 36565645 8 24 theme glutamine 1510:1518 arg1 enhancement 1602:1612 the enhancement 1598:1612 the enhancement of G6PD glycosylation 1598:1634 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 8 24 theme glutamine 1510:1518 arg1 mechanisms 1496:1505 the central mechanisms 1484:1505 the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier 1484:1592 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 6 25 theme oxidative 1067:1075 arg1 stress 1077:1082 oxidative stress 1067:1082 oxidative stress 1067:1082 Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. 36565645 0 26 theme septic 132:137 arg1 mice 139:142 burned septic mice 125:142 burned septic mice 125:142 Glutamine promotes O-GlcNAcylation of G6PD and inhibits AGR2 S-glutathionylation to maintain the intestinal mucus barrier in burned septic mice. 36565645 5 27 theme MUC2 877:880 arg1 precursors 882:891 MUC2 precursors 877:891 MUC2 precursors 877:891 Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. 36565645 5 28 theme MUC2 937:940 arg1 synthesis 917:925 the synthesis 913:925 the synthesis of mature MUC2 913:940 Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. 36565645 7 29 theme G6PD 1240:1243 arg1 formation 1255:1263 G6PD homodimer formation 1240:1263 G6PD homodimer formation 1240:1263 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 2 30 theme burn 396:399 arg1 injury 401:406 burn injury 396:406 burn injury 396:406 Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. 36565645 0 31 theme burned 125:130 arg1 mice 139:142 burned septic mice 125:142 burned septic mice 125:142 Glutamine promotes O-GlcNAcylation of G6PD and inhibits AGR2 S-glutathionylation to maintain the intestinal mucus barrier in burned septic mice. 36565645 2 32 theme energy 271:276 arg1 substance 278:286 a vital energy substance 263:286 a vital energy substance for goblet cells 263:303 Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. 36565645 2 32 theme energy 271:276 arg1 Glutamine 250:258 Glutamine 250:258 Glutamine 250:258 Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. 36565645 1 33 theme intestinal 190:199 arg1 barrier 208:214 the intestinal mucosa barrier 186:214 the intestinal mucosa barrier 186:214 Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. 36565645 5 34 theme mature 930:935 arg1 MUC2 937:940 mature MUC2 930:940 mature MUC2 930:940 Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. 36565645 1 35 theme mucosa 201:206 arg1 barrier 208:214 the intestinal mucosa barrier 186:214 the intestinal mucosa barrier 186:214 Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. 36565645 4 36 theme MUC2 738:741 arg1 modification 722:733 the posttranslational modification 700:733 the posttranslational modification of MUC2 700:741 We found that anterior gradient-2 (AGR2) plays a key role in the posttranslational modification of MUC2. 36565645 2 37 theme mucus 376:380 arg1 barrier 382:388 the intestinal mucus barrier 361:388 the intestinal mucus barrier 361:388 Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. 36565645 0 38 theme G6PD 38:41 arg1 O-GlcNAcylation 19:33 O-GlcNAcylation 19:33 O-GlcNAcylation of G6PD 19:41 Glutamine promotes O-GlcNAcylation of G6PD and inhibits AGR2 S-glutathionylation to maintain the intestinal mucus barrier in burned septic mice. 36565645 3 39 theme MUC2 581:584 arg1 modification 556:567 modification 556:567 modification 556:567 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 3 39 theme MUC2 581:584 arg1 synthesis 542:550 synthesis 542:550 synthesis 542:550 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 5 40 theme burn 772:775 arg1 sepsis 777:782 burn sepsis 772:782 burn sepsis 772:782 Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. 36565645 1 41 theme barrier 208:214 arg1 defence 175:181 defence 175:181 defence of the intestinal mucosa barrier 175:214 Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. 36565645 0 42 theme AGR2 56:59 arg1 S-glutathionylation 61:79 AGR2 S-glutathionylation 56:79 AGR2 S-glutathionylation to maintain the intestinal mucus barrier in burned septic mice 56:142 Glutamine promotes O-GlcNAcylation of G6PD and inhibits AGR2 S-glutathionylation to maintain the intestinal mucus barrier in burned septic mice. 36565645 8 43 theme MUC2 1533:1536 arg1 maturation 1538:1547 MUC2 maturation 1533:1547 MUC2 maturation 1533:1547 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 5 44 dep processing 846:855 arg1 the 842:844 the 842:844 the 842:844 Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. 36565645 7 45 theme AGR2 1315:1318 arg1 S-glutathionylation 1320:1338 AGR2 S-glutathionylation 1315:1338 AGR2 S-glutathionylation 1315:1338 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 8 46 theme G6PD 1617:1620 arg1 glycosylation 1622:1634 G6PD glycosylation 1617:1634 G6PD glycosylation 1617:1634 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 3 47 theme cellular 607:614 arg1 models 616:621 animal and cellular models 596:621 animal and cellular models of burn sepsis 596:636 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 7 48 theme NADPH 1279:1283 arg1 synthesis 1285:1293 NADPH synthesis 1279:1293 NADPH synthesis 1279:1293 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 6 49 theme key 1040:1042 arg1 NADPH 973:977 NADPH 973:977 NADPH 973:977 Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. 36565645 6 49 theme key 1040:1042 arg1 molecule 1044:1051 a key molecule 1038:1051 a key molecule 1038:1051 Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. 36565645 3 50 from effects 514:520 arg1 modification 556:567 modification 556:567 modification 556:567 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 3 50 from effects 514:520 arg1 synthesis 542:550 synthesis 542:550 synthesis 542:550 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 4 51 theme posttranslational 704:720 arg1 modification 722:733 the posttranslational modification 700:733 the posttranslational modification of MUC2 700:741 We found that anterior gradient-2 (AGR2) plays a key role in the posttranslational modification of MUC2. 36565645 0 52 from barrier 114:120 arg1 mice 139:142 burned septic mice 125:142 burned septic mice 125:142 Glutamine promotes O-GlcNAcylation of G6PD and inhibits AGR2 S-glutathionylation to maintain the intestinal mucus barrier in burned septic mice. 36565645 4 53 theme anterior 653:660 arg1 AGR2 674:677 AGR2 674:677 AGR2 674:677 We found that anterior gradient-2 (AGR2) plays a key role in the posttranslational modification of MUC2. 36565645 4 53 theme anterior 653:660 arg1 gradient-2 662:671 anterior gradient-2 653:671 anterior gradient-2 (AGR2) 653:678 We found that anterior gradient-2 (AGR2) plays a key role in the posttranslational modification of MUC2. 36565645 7 54 theme MUC2 1354:1357 arg1 maturation 1359:1368 MUC2 maturation 1354:1368 MUC2 maturation 1354:1368 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 8 55 theme intestinal 1569:1578 arg1 barrier 1586:1592 the intestinal mucus barrier 1565:1592 the intestinal mucus barrier 1565:1592 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 7 56 link O-linked 1133:1140 arg1 O-GlcNAc 1163:1170 O-GlcNAc 1163:1170 O-GlcNAc 1163:1170 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 7 56 link O-linked 1133:1140 arg1 N-acetylglucosamine 1142:1160 O-linked N-acetylglucosamine 1133:1160 O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD 1133:1192 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 3 57 theme animal 596:601 arg1 models 616:621 animal and cellular models 596:621 animal and cellular models of burn sepsis 596:636 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 5 58 theme Oxidative 744:752 arg1 stress 754:759 Oxidative stress 744:759 Oxidative stress induced by burn sepsis 744:782 Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. 36565645 7 59 theme hexosamine 1202:1211 arg1 pathway 1213:1219 the hexosamine pathway 1198:1219 the hexosamine pathway 1198:1219 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 6 60 theme Further 943:949 arg1 studies 951:957 Further studies 943:957 Further studies 943:957 Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. 36565645 2 61 theme intestinal 365:374 arg1 barrier 382:388 the intestinal mucus barrier 361:388 the intestinal mucus barrier 361:388 Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. 36565645 5 62 theme precursors 882:891 arg1 modification 861:872 modification 861:872 modification 861:872 Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. 36565645 5 62 theme precursors 882:891 arg1 processing 846:855 processing 846:855 processing 846:855 Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. 36565645 6 63 theme glucose-6-phosphate 993:1011 arg1 G6PD 1028:1031 G6PD 1028:1031 G6PD 1028:1031 Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. 36565645 6 63 theme glucose-6-phosphate 993:1011 arg1 dehydrogenase 1013:1025 glucose-6-phosphate dehydrogenase 993:1025 glucose-6-phosphate dehydrogenase (G6PD) 993:1032 Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. 36565645 8 64 theme S-glutathionylation 1659:1677 arg1 inhibition 1640:1649 inhibition 1640:1649 inhibition of AGR2 S-glutathionylation 1640:1677 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 8 64 theme S-glutathionylation 1659:1677 arg1 enhancement 1602:1612 the enhancement 1598:1612 the enhancement of G6PD glycosylation 1598:1634 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 8 64 theme S-glutathionylation 1659:1677 arg1 mechanisms 1496:1505 the central mechanisms 1484:1505 the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier 1484:1592 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 3 65 theme sepsis 631:636 arg1 models 616:621 animal and cellular models 596:621 animal and cellular models of burn sepsis 596:636 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 3 66 theme mucin 572:576 arg1 MUC2 581:584 mucin 2 (MUC2) 572:585 mucin 2 (MUC2) 572:585 This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. 36565645 5 67 theme AGR2 820:823 arg1 S-glutathionylation 797:815 the S-glutathionylation 793:815 the S-glutathionylation of AGR2 793:823 Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. 36565645 8 68 theme AGR2 1654:1657 arg1 S-glutathionylation 1659:1677 AGR2 S-glutathionylation 1654:1677 AGR2 S-glutathionylation 1654:1677 Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation. 36565645 7 69 theme O-linked 1133:1140 arg1 O-GlcNAc 1163:1170 O-GlcNAc 1163:1170 O-GlcNAc 1163:1170 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36565645 7 69 theme O-linked 1133:1140 arg1 N-acetylglucosamine 1142:1160 O-linked N-acetylglucosamine 1133:1160 O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD 1133:1192 Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. 36376492 11 0 theme mice 1825:1828 arg1 RVs 1811:1813 the RVs 1807:1813 the RVs of Ogt-Tg mice 1807:1828 In addition to increasing the levels of phosphorylated Smad2, IH4W promoted cardiac fibrosis in the RVs of Ogt-Tg mice. 36376492 1 1 theme cardiac 290:296 arg1 remodeling 298:307 cardiac remodeling 290:307 cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65 290:583 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 4 2 theme Total 807:811 arg1 levels 829:834 Total O-GlcNAcylation levels 807:834 Total O-GlcNAcylation levels 807:834 Total O-GlcNAcylation levels were significantly increased in WT and Ogt-Tg mice after IH4W vs. normoxia. 36376492 6 3 theme IH4W-induced 1105:1116 arg1 dysfunction 1136:1146 IH4W-induced right ventricular dysfunction 1105:1146 IH4W-induced right ventricular dysfunction 1105:1146 Echocardiography revealed IH4W-induced right ventricular dysfunction. 36376492 2 4 from weeks 660:664 arg1 study 688:692 the present study 676:692 the present study 676:692 Because this effect is time dependent, we exposed Ogt-Tg mice to IH for 4 weeks (IH4W) in the present study. 36376492 11 5 theme Smad2 1766:1770 arg1 levels 1741:1746 the levels 1737:1746 the levels of phosphorylated Smad2 1737:1770 In addition to increasing the levels of phosphorylated Smad2, IH4W promoted cardiac fibrosis in the RVs of Ogt-Tg mice. 36376492 1 6 theme factor 480:485 arg1 NF-κB 496:500 NF-κB 496:500 NF-κB 496:500 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 6 theme factor 480:485 arg1 B 493:493 nuclear factor kappa B 472:493 nuclear factor kappa B (NF-κB) 472:501 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 7 theme factor 433:438 arg1 NFAT 462:465 NFAT 462:465 NFAT 462:465 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 7 theme factor 433:438 arg1 cells 455:459 nuclear factor of activated T cells 425:459 nuclear factor of activated T cells (NFAT) 425:466 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 0 8 theme fibrosis 130:137 arg1 enhancement 87:97 enhancement 87:97 enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia 87:187 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 5 9 theme fibrosis 1005:1012 arg1 signs 972:976 significantly exacerbated signs 946:976 significantly exacerbated signs of cardiac hypertrophy and fibrosis 946:1012 After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). 36376492 11 10 theme cardiac 1787:1793 arg1 fibrosis 1795:1802 cardiac fibrosis 1787:1802 cardiac fibrosis in the RVs of Ogt-Tg mice 1787:1828 In addition to increasing the levels of phosphorylated Smad2, IH4W promoted cardiac fibrosis in the RVs of Ogt-Tg mice. 36376492 1 11 theme O-linked 227:234 arg1 O-GlcNAcylation 263:277 O-GlcNAcylation 263:277 O-GlcNAcylation 263:277 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 11 theme O-linked 227:234 arg1 N-acetylglucosaminylation 236:260 augmented O-linked N-acetylglucosaminylation 217:260 augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) 217:278 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 8 12 theme mice 1381:1384 arg1 RVs 1367:1369 the RVs 1363:1369 the RVs of Ogt-Tg mice 1363:1384 Mitophagy, which is associated with cardiac dysfunction, was increased in the RVs of Ogt-Tg mice after IH4W. 36376492 12 13 theme Smad2 2047:2051 arg1 activation 2053:2062 Smad2 activation 2047:2062 Smad2 activation 2047:2062 Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively. 36376492 3 14 dep wild-type 757:765 arg1 WT 768:769 WT 768:769 WT 768:769 O-GlcNAcylation was significantly enhanced in Ogt-Tg mice vs. wild-type (WT) mice exposed to normoxia and IH4W. 36376492 1 15 theme of 440:441 arg1 NFAT 462:465 NFAT 462:465 NFAT 462:465 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 15 theme of 440:441 arg1 cells 455:459 nuclear factor of activated T cells 425:459 nuclear factor of activated T cells (NFAT) 425:466 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 16 theme NF-κB 575:579 arg1 p65 581:583 NF-κB p65 575:583 NF-κB p65 575:583 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 0 17 theme intermittent 168:179 arg1 hypoxia 181:187 long-term intermittent hypoxia 158:187 long-term intermittent hypoxia 158:187 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 5 18 theme hypertrophy 989:999 arg1 signs 972:976 significantly exacerbated signs 946:976 significantly exacerbated signs of cardiac hypertrophy and fibrosis 946:1012 After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). 36376492 9 19 theme phosphorylated 1425:1438 arg1 protein 1456:1462 phosphorylated dynamin-related protein 1 1425:1464 phosphorylated dynamin-related protein 1 (p-Drp1) 1425:1473 Furthermore, the levels of phosphorylated dynamin-related protein 1 (p-Drp1) were significantly increased, and the expression of mitofusin-2 (MFN2) was significantly decreased. 36376492 9 19 theme phosphorylated 1425:1438 arg1 p-Drp1 1467:1472 p-Drp1 1467:1472 p-Drp1 1467:1472 Furthermore, the levels of phosphorylated dynamin-related protein 1 (p-Drp1) were significantly increased, and the expression of mitofusin-2 (MFN2) was significantly decreased. 36376492 6 20 theme ventricular 1124:1134 arg1 dysfunction 1136:1146 IH4W-induced right ventricular dysfunction 1105:1146 IH4W-induced right ventricular dysfunction 1105:1146 Echocardiography revealed IH4W-induced right ventricular dysfunction. 36376492 12 21 theme p-Drp-1/MFN2 2023:2034 arg1 ratio 2036:2040 an increased p-Drp-1/MFN2 ratio 2010:2040 an increased p-Drp-1/MFN2 ratio 2010:2040 Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively. 36376492 11 22 dep increasing 1726:1735 arg1 addition 1714:1721 addition 1714:1721 addition 1714:1721 In addition to increasing the levels of phosphorylated Smad2, IH4W promoted cardiac fibrosis in the RVs of Ogt-Tg mice. 36376492 1 23 theme acute 369:373 arg1 hypoxia 397:403 acute (2-week) intermittent hypoxia 369:403 acute (2-week) intermittent hypoxia (IH) 369:408 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 23 theme acute 369:373 arg1 IH 406:407 IH 406:407 IH 406:407 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 9 24 theme protein 1456:1462 arg1 levels 1415:1420 the levels 1411:1420 the levels of phosphorylated dynamin-related protein 1 (p-Drp1) 1411:1473 Furthermore, the levels of phosphorylated dynamin-related protein 1 (p-Drp1) were significantly increased, and the expression of mitofusin-2 (MFN2) was significantly decreased. 36376492 7 25 theme GSK-3β 1164:1169 arg1 levels 1171:1176 Phosphorylated GSK-3β levels 1149:1176 Phosphorylated GSK-3β levels 1149:1176 Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. 36376492 1 26 theme 2-week 376:381 arg1 hypoxia 397:403 acute (2-week) intermittent hypoxia 369:403 acute (2-week) intermittent hypoxia (IH) 369:408 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 26 theme 2-week 376:381 arg1 IH 406:407 IH 406:407 IH 406:407 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 27 theme activated 443:451 arg1 NFAT 462:465 NFAT 462:465 NFAT 462:465 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 27 theme activated 443:451 arg1 cells 455:459 nuclear factor of activated T cells 425:459 nuclear factor of activated T cells (NFAT) 425:466 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 3 28 gly O-GlcNAcylation 695:709 arg1 mice 748:751 Ogt-Tg mice 741:751 Ogt-Tg mice 741:751 O-GlcNAcylation was significantly enhanced in Ogt-Tg mice vs. wild-type (WT) mice exposed to normoxia and IH4W. 36376492 3 28 gly O-GlcNAcylation 695:709 arg1 mice 772:775 wild-type (WT) mice 757:775 wild-type (WT) mice 757:775 O-GlcNAcylation was significantly enhanced in Ogt-Tg mice vs. wild-type (WT) mice exposed to normoxia and IH4W. 36376492 1 29 theme nuclear 425:431 arg1 NFAT 462:465 NFAT 462:465 NFAT 462:465 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 29 theme nuclear 425:431 arg1 cells 455:459 nuclear factor of activated T cells 425:459 nuclear factor of activated T cells (NFAT) 425:466 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 3 30 theme wild-type 757:765 arg1 mice 772:775 wild-type (WT) mice 757:775 wild-type (WT) mice 757:775 O-GlcNAcylation was significantly enhanced in Ogt-Tg mice vs. wild-type (WT) mice exposed to normoxia and IH4W. 36376492 1 31 theme intermittent 384:395 arg1 hypoxia 397:403 acute (2-week) intermittent hypoxia 369:403 acute (2-week) intermittent hypoxia (IH) 369:408 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 31 theme intermittent 384:395 arg1 IH 406:407 IH 406:407 IH 406:407 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 12 32 theme right 1890:1894 arg1 dysfunction 1908:1918 IH4W-induced right ventricular dysfunction 1877:1918 IH4W-induced right ventricular dysfunction 1877:1918 Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively. 36376492 1 33 theme synthase 539:546 arg1 GSK-3β 563:568 GSK-3β 563:568 GSK-3β 563:568 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 33 theme synthase 539:546 arg1 beta 557:560 glycogen synthase kinase 3 beta 530:560 glycogen synthase kinase 3 beta (GSK-3β) 530:569 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 10 34 theme human 1578:1582 arg1 cells 1601:1605 human embryonic kidney cells 1578:1605 human embryonic kidney cells 1578:1605 In human embryonic kidney cells, mitochondrial uncoupler-induced mitochondrial dysfunction was accelerated in Ogt-overexpressing cells. 36376492 0 35 theme Augmented 0:8 arg1 O-GlcNAcylation 10:24 Augmented O-GlcNAcylation 0:24 Augmented O-GlcNAcylation 0:24 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 1 36 theme O-GlcNAc 312:319 arg1 mice 353:356 O-GlcNAc transferase-transgenic (Ogt-Tg) mice 312:356 O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65 312:583 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 7 37 theme p65 1261:1263 arg1 levels 1265:1270 phosphorylated NF-κB p65 levels 1240:1270 phosphorylated NF-κB p65 levels 1240:1270 Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. 36376492 7 38 theme phosphorylated 1240:1253 arg1 levels 1265:1270 phosphorylated NF-κB p65 levels 1240:1270 phosphorylated NF-κB p65 levels 1240:1270 Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. 36376492 10 39 theme kidney 1594:1599 arg1 cells 1601:1605 human embryonic kidney cells 1578:1605 human embryonic kidney cells 1578:1605 In human embryonic kidney cells, mitochondrial uncoupler-induced mitochondrial dysfunction was accelerated in Ogt-overexpressing cells. 36376492 0 40 theme ventricular 44:54 arg1 dysfunction 56:66 right ventricular dysfunction 38:66 right ventricular dysfunction 38:66 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 10 41 theme uncoupler-induced 1622:1638 arg1 dysfunction 1654:1664 mitochondrial uncoupler-induced mitochondrial dysfunction 1608:1664 mitochondrial uncoupler-induced mitochondrial dysfunction 1608:1664 In human embryonic kidney cells, mitochondrial uncoupler-induced mitochondrial dysfunction was accelerated in Ogt-overexpressing cells. 36376492 7 42 theme WT 1212:1213 arg1 mice 1215:1218 WT mice 1212:1218 WT mice 1212:1218 Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. 36376492 0 43 from mice 142:145 arg1 enhancement 87:97 enhancement 87:97 enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia 87:187 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 10 44 theme Ogt-overexpressing 1685:1702 arg1 cells 1704:1708 Ogt-overexpressing cells 1685:1708 Ogt-overexpressing cells 1685:1708 In human embryonic kidney cells, mitochondrial uncoupler-induced mitochondrial dysfunction was accelerated in Ogt-overexpressing cells. 36376492 12 45 theme GSK-3β 1989:1994 arg1 inactivation 1996:2007 GSK-3β inactivation 1989:2007 GSK-3β inactivation 1989:2007 Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively. 36376492 0 46 from fibrosis 130:137 arg1 mice 142:145 mice 142:145 mice exposed to long-term intermittent hypoxia 142:187 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 7 47 theme Phosphorylated 1149:1162 arg1 levels 1171:1176 Phosphorylated GSK-3β levels 1149:1176 Phosphorylated GSK-3β levels 1149:1176 Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. 36376492 11 48 theme Ogt-Tg 1818:1823 arg1 mice 1825:1828 Ogt-Tg mice 1818:1828 Ogt-Tg mice 1818:1828 In addition to increasing the levels of phosphorylated Smad2, IH4W promoted cardiac fibrosis in the RVs of Ogt-Tg mice. 36376492 5 49 theme exacerbated 960:970 arg1 signs 972:976 significantly exacerbated signs 946:976 significantly exacerbated signs of cardiac hypertrophy and fibrosis 946:1012 After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). 36376492 11 50 from fibrosis 1795:1802 arg1 RVs 1811:1813 the RVs 1807:1813 the RVs of Ogt-Tg mice 1807:1828 In addition to increasing the levels of phosphorylated Smad2, IH4W promoted cardiac fibrosis in the RVs of Ogt-Tg mice. 36376492 2 51 theme present 680:686 arg1 study 688:692 the present study 676:692 the present study 676:692 Because this effect is time dependent, we exposed Ogt-Tg mice to IH for 4 weeks (IH4W) in the present study. 36376492 1 52 theme nuclear 472:478 arg1 NF-κB 496:500 NF-κB 496:500 NF-κB 496:500 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 52 theme nuclear 472:478 arg1 B 493:493 nuclear factor kappa B 472:493 nuclear factor kappa B (NF-κB) 472:501 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 53 from remodeling 298:307 arg1 mice 353:356 O-GlcNAc transferase-transgenic (Ogt-Tg) mice 312:356 O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65 312:583 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 54 theme kappa 487:491 arg1 NF-κB 496:500 NF-κB 496:500 NF-κB 496:500 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 54 theme kappa 487:491 arg1 B 493:493 nuclear factor kappa B 472:493 nuclear factor kappa B (NF-κB) 472:501 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 0 55 from hypertrophy 102:112 arg1 mice 142:145 mice 142:145 mice exposed to long-term intermittent hypoxia 142:187 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 11 56 theme phosphorylated 1751:1764 arg1 Smad2 1766:1770 phosphorylated Smad2 1751:1770 phosphorylated Smad2 1751:1770 In addition to increasing the levels of phosphorylated Smad2, IH4W promoted cardiac fibrosis in the RVs of Ogt-Tg mice. 36376492 1 57 theme augmented 217:225 arg1 O-GlcNAcylation 263:277 O-GlcNAcylation 263:277 O-GlcNAcylation 263:277 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 57 theme augmented 217:225 arg1 N-acetylglucosaminylation 236:260 augmented O-linked N-acetylglucosaminylation 217:260 augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) 217:278 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 4 58 theme WT 868:869 arg1 mice 882:885 WT and Ogt-Tg mice 868:885 WT and Ogt-Tg mice 868:885 Total O-GlcNAcylation levels were significantly increased in WT and Ogt-Tg mice after IH4W vs. normoxia. 36376492 0 59 from enhancement 87:97 arg1 mice 142:145 mice 142:145 mice exposed to long-term intermittent hypoxia 142:187 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 0 60 theme long-term 158:166 arg1 hypoxia 181:187 long-term intermittent hypoxia 158:187 long-term intermittent hypoxia 158:187 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 5 61 theme right 1021:1025 arg1 RVs 1039:1041 RVs 1039:1041 RVs 1039:1041 After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). 36376492 5 61 theme right 1021:1025 arg1 ventricles 1027:1036 the right ventricles 1017:1036 the right ventricles (RVs) but not the left ventricles (LVs) 1017:1076 After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). 36376492 4 62 theme O-GlcNAcylation 813:827 arg1 levels 829:834 Total O-GlcNAcylation levels 807:834 Total O-GlcNAcylation levels 807:834 Total O-GlcNAcylation levels were significantly increased in WT and Ogt-Tg mice after IH4W vs. normoxia. 36376492 5 63 theme cardiac 981:987 arg1 hypertrophy 989:999 cardiac hypertrophy 981:999 cardiac hypertrophy 981:999 After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). 36376492 0 64 from mitophagy 115:123 arg1 mice 142:145 mice 142:145 mice exposed to long-term intermittent hypoxia 142:187 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 1 65 theme p65 581:583 arg1 O-GlcNAcylation 511:525 the O-GlcNAcylation 507:525 the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65 507:583 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 66 theme T 453:453 arg1 NFAT 462:465 NFAT 462:465 NFAT 462:465 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 66 theme T 453:453 arg1 cells 455:459 nuclear factor of activated T cells 425:459 nuclear factor of activated T cells (NFAT) 425:466 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 9 67 theme dynamin-related 1440:1454 arg1 protein 1456:1462 phosphorylated dynamin-related protein 1 1425:1464 phosphorylated dynamin-related protein 1 (p-Drp1) 1425:1473 Furthermore, the levels of phosphorylated dynamin-related protein 1 (p-Drp1) were significantly increased, and the expression of mitofusin-2 (MFN2) was significantly decreased. 36376492 9 67 theme dynamin-related 1440:1454 arg1 p-Drp1 1467:1472 p-Drp1 1467:1472 p-Drp1 1467:1472 Furthermore, the levels of phosphorylated dynamin-related protein 1 (p-Drp1) were significantly increased, and the expression of mitofusin-2 (MFN2) was significantly decreased. 36376492 6 68 theme right 1118:1122 arg1 dysfunction 1136:1146 IH4W-induced right ventricular dysfunction 1105:1146 IH4W-induced right ventricular dysfunction 1105:1146 Echocardiography revealed IH4W-induced right ventricular dysfunction. 36376492 12 69 theme increased 2013:2021 arg1 ratio 2036:2040 an increased p-Drp-1/MFN2 ratio 2010:2040 an increased p-Drp-1/MFN2 ratio 2010:2040 Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively. 36376492 3 70 theme Ogt-Tg 741:746 arg1 mice 748:751 Ogt-Tg mice 741:751 Ogt-Tg mice 741:751 O-GlcNAcylation was significantly enhanced in Ogt-Tg mice vs. wild-type (WT) mice exposed to normoxia and IH4W. 36376492 0 71 theme hypertrophy 102:112 arg1 enhancement 87:97 enhancement 87:97 enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia 87:187 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 12 72 theme IH4W-induced 1877:1888 arg1 dysfunction 1908:1918 IH4W-induced right ventricular dysfunction 1877:1918 IH4W-induced right ventricular dysfunction 1877:1918 Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively. 36376492 1 73 link O-linked 227:234 arg1 O-GlcNAcylation 263:277 O-GlcNAcylation 263:277 O-GlcNAcylation 263:277 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 73 link O-linked 227:234 arg1 N-acetylglucosaminylation 236:260 augmented O-linked N-acetylglucosaminylation 217:260 augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) 217:278 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 8 74 theme Ogt-Tg 1374:1379 arg1 mice 1381:1384 Ogt-Tg mice 1374:1384 Ogt-Tg mice 1374:1384 Mitophagy, which is associated with cardiac dysfunction, was increased in the RVs of Ogt-Tg mice after IH4W. 36376492 0 75 theme mitophagy 115:123 arg1 enhancement 87:97 enhancement 87:97 enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia 87:187 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 5 76 theme left 1056:1059 arg1 LVs 1073:1075 LVs 1073:1075 LVs 1073:1075 After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). 36376492 5 76 theme left 1056:1059 arg1 ventricles 1061:1070 the left ventricles 1052:1070 the right ventricles (RVs) but not the left ventricles (LVs) 1017:1076 After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). 36376492 12 77 theme ventricular 1896:1906 arg1 dysfunction 1908:1918 IH4W-induced right ventricular dysfunction 1877:1918 IH4W-induced right ventricular dysfunction 1877:1918 Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively. 36376492 4 78 theme Ogt-Tg 875:880 arg1 mice 882:885 WT and Ogt-Tg mice 868:885 WT and Ogt-Tg mice 868:885 Total O-GlcNAcylation levels were significantly increased in WT and Ogt-Tg mice after IH4W vs. normoxia. 36376492 1 79 theme glycogen 530:537 arg1 GSK-3β 563:568 GSK-3β 563:568 GSK-3β 563:568 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 79 theme glycogen 530:537 arg1 beta 557:560 glycogen synthase kinase 3 beta 530:560 glycogen synthase kinase 3 beta (GSK-3β) 530:569 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 12 80 theme augmented 1837:1845 arg1 O-GlcNAcylation 1847:1861 augmented O-GlcNAcylation 1837:1861 augmented O-GlcNAcylation 1837:1861 Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively. 36376492 1 81 theme kinase 548:553 arg1 GSK-3β 563:568 GSK-3β 563:568 GSK-3β 563:568 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 81 theme kinase 548:553 arg1 beta 557:560 glycogen synthase kinase 3 beta 530:560 glycogen synthase kinase 3 beta (GSK-3β) 530:569 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 7 82 dep increased 1183:1191 arg1 whereas 1232:1238 whereas 1232:1238 whereas 1232:1238 Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. 36376492 7 83 theme NF-κB 1255:1259 arg1 levels 1265:1270 phosphorylated NF-κB p65 levels 1240:1270 phosphorylated NF-κB p65 levels 1240:1270 Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. 36376492 2 84 theme Ogt-Tg 636:641 arg1 mice 643:646 Ogt-Tg mice 636:646 Ogt-Tg mice 636:646 Because this effect is time dependent, we exposed Ogt-Tg mice to IH for 4 weeks (IH4W) in the present study. 36376492 1 85 theme beta 557:560 arg1 O-GlcNAcylation 511:525 the O-GlcNAcylation 507:525 the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65 507:583 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 0 86 theme right 38:42 arg1 dysfunction 56:66 right ventricular dysfunction 38:66 right ventricular dysfunction 38:66 Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia. 36376492 1 87 theme transferase-transgenic 321:342 arg1 mice 353:356 O-GlcNAc transferase-transgenic (Ogt-Tg) mice 312:356 O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65 312:583 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 1 88 theme Ogt-Tg 345:350 arg1 mice 353:356 O-GlcNAc transferase-transgenic (Ogt-Tg) mice 312:356 O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65 312:583 Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. 36376492 8 89 theme cardiac 1325:1331 arg1 dysfunction 1333:1343 cardiac dysfunction 1325:1343 cardiac dysfunction 1325:1343 Mitophagy, which is associated with cardiac dysfunction, was increased in the RVs of Ogt-Tg mice after IH4W. 36376492 10 90 theme embryonic 1584:1592 arg1 cells 1601:1605 human embryonic kidney cells 1578:1605 human embryonic kidney cells 1578:1605 In human embryonic kidney cells, mitochondrial uncoupler-induced mitochondrial dysfunction was accelerated in Ogt-overexpressing cells. 36376492 9 91 theme mitofusin-2 1527:1537 arg1 expression 1513:1522 the expression 1509:1522 the expression of mitofusin-2 (MFN2) 1509:1544 Furthermore, the levels of phosphorylated dynamin-related protein 1 (p-Drp1) were significantly increased, and the expression of mitofusin-2 (MFN2) was significantly decreased. 36376492 10 92 theme mitochondrial 1640:1652 arg1 dysfunction 1654:1664 mitochondrial uncoupler-induced mitochondrial dysfunction 1608:1664 mitochondrial uncoupler-induced mitochondrial dysfunction 1608:1664 In human embryonic kidney cells, mitochondrial uncoupler-induced mitochondrial dysfunction was accelerated in Ogt-overexpressing cells. 36376492 10 93 theme mitochondrial 1608:1620 arg1 dysfunction 1654:1664 mitochondrial uncoupler-induced mitochondrial dysfunction 1608:1664 mitochondrial uncoupler-induced mitochondrial dysfunction 1608:1664 In human embryonic kidney cells, mitochondrial uncoupler-induced mitochondrial dysfunction was accelerated in Ogt-overexpressing cells. 36376492 5 94 theme Ogt-Tg 924:929 arg1 mice 931:934 Ogt-Tg mice 924:934 Ogt-Tg mice 924:934 After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). 36376492 7 95 theme Ogt-Tg 1196:1201 arg1 mice 1203:1206 Ogt-Tg mice 1196:1206 Ogt-Tg mice 1196:1206 Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. 36316364 3 0 theme patients 470:477 arg1 cohort 456:461 a cross-sectional cohort 438:461 a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298) 438:518 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 1 1 theme non-protein 211:221 arg1 antigens 223:230 non-protein antigens 211:230 non-protein antigens 211:230 Type 1 diabetes (T1D) is an autoimmune disease, characterized by the presence of autoantibodies to protein and non-protein antigens. 36316364 5 2 theme B 696:696 arg1 antigens 698:705 blood group A and B antigens 678:705 blood group A and B antigens 678:705 Clusters enriched for aminoglycosides, blood group A and B antigens, glycolipids, ganglio-series, and O-linked glycans are associated with progression to T1D. 36316364 6 3 theme related 830:836 arg1 sisomicin 859:867 sisomicin 859:867 sisomicin 859:867 ACAs against gentamicin and its related structures, G418 and sisomicin, are also associated with islet autoimmunity. 36316364 6 3 theme related 830:836 arg1 G418 850:853 G418 850:853 G418 850:853 ACAs against gentamicin and its related structures, G418 and sisomicin, are also associated with islet autoimmunity. 36316364 6 3 theme related 830:836 arg1 structures 838:847 its related structures 826:847 its related structures 826:847 ACAs against gentamicin and its related structures, G418 and sisomicin, are also associated with islet autoimmunity. 36316364 4 4 theme glycan 616:621 arg1 function 623:630 glycan function 616:630 glycan function class 616:636 We identify 11 clusters of ACAs associated with glycan function class. 36316364 5 5 link O-linked 741:748 arg1 glycans 750:756 O-linked glycans 741:756 O-linked glycans 741:756 Clusters enriched for aminoglycosides, blood group A and B antigens, glycolipids, ganglio-series, and O-linked glycans are associated with progression to T1D. 36316364 7 6 theme potential 1022:1030 arg1 biomarkers 1032:1041 potential biomarkers 1022:1041 potential biomarkers for T1D 1022:1049 ACAs improve discrimination of T1D status of individuals over a model with only clinical variables and are potential biomarkers for T1D. 36316364 3 7 theme controls 501:508 arg1 cohort 456:461 a cross-sectional cohort 438:461 a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298) 438:518 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 0 8 theme type 83:86 arg1 diabetes 90:97 type 1 diabetes 83:97 type 1 diabetes 83:97 Use of a glycomics array to establish the anti-carbohydrate antibody repertoire in type 1 diabetes. 36316364 7 9 theme T1D 946:948 arg1 status 950:955 T1D status 946:955 T1D status of individuals over a model with only clinical variables 946:1012 ACAs improve discrimination of T1D status of individuals over a model with only clinical variables and are potential biomarkers for T1D. 36316364 6 10 theme islet 895:899 arg1 autoimmunity 901:912 islet autoimmunity 895:912 islet autoimmunity 895:912 ACAs against gentamicin and its related structures, G418 and sisomicin, are also associated with islet autoimmunity. 36316364 1 11 theme autoimmune 128:137 arg1 diabetes 107:114 Type 1 diabetes 100:114 Type 1 diabetes (T1D) 100:120 Type 1 diabetes (T1D) is an autoimmune disease, characterized by the presence of autoantibodies to protein and non-protein antigens. 36316364 1 11 theme autoimmune 128:137 arg1 disease 139:145 an autoimmune disease 125:145 an autoimmune disease 125:145 Type 1 diabetes (T1D) is an autoimmune disease, characterized by the presence of autoantibodies to protein and non-protein antigens. 36316364 5 12 theme blood 678:682 arg1 A 690:690 blood group A 678:690 blood group A 678:690 Clusters enriched for aminoglycosides, blood group A and B antigens, glycolipids, ganglio-series, and O-linked glycans are associated with progression to T1D. 36316364 3 13 theme healthy 493:499 arg1 controls 501:508 healthy controls 493:508 healthy controls (n = 298) 493:518 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 3 13 theme healthy 493:499 arg1 n = 298 511:517 n = 298 511:517 n = 298 511:517 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 7 14 theme clinical 995:1002 arg1 variables 1004:1012 only clinical variables 990:1012 only clinical variables 990:1012 ACAs improve discrimination of T1D status of individuals over a model with only clinical variables and are potential biomarkers for T1D. 36316364 5 15 theme group 684:688 arg1 A 690:690 blood group A 678:690 blood group A 678:690 Clusters enriched for aminoglycosides, blood group A and B antigens, glycolipids, ganglio-series, and O-linked glycans are associated with progression to T1D. 36316364 2 16 theme antibodies 297:306 arg1 identification 252:265 the identification 248:265 the identification of specific anti-carbohydrate antibodies (ACAs) that are associated with pathogenesis and progression to T1D 248:374 Here we report the identification of specific anti-carbohydrate antibodies (ACAs) that are associated with pathogenesis and progression to T1D. 36316364 4 17 theme ACAs 595:598 arg1 clusters 583:590 11 clusters 580:590 11 clusters of ACAs associated with glycan function class 580:636 We identify 11 clusters of ACAs associated with glycan function class. 36316364 2 18 theme anti-carbohydrate 279:295 arg1 ACAs 309:312 ACAs 309:312 ACAs 309:312 Here we report the identification of specific anti-carbohydrate antibodies (ACAs) that are associated with pathogenesis and progression to T1D. 36316364 2 18 theme anti-carbohydrate 279:295 arg1 antibodies 297:306 specific anti-carbohydrate antibodies 270:306 specific anti-carbohydrate antibodies (ACAs) that are associated with pathogenesis and progression to T1D 270:374 Here we report the identification of specific anti-carbohydrate antibodies (ACAs) that are associated with pathogenesis and progression to T1D. 36316364 0 19 theme glycomics 9:17 arg1 array 19:23 a glycomics array 7:23 a glycomics array 7:23 Use of a glycomics array to establish the anti-carbohydrate antibody repertoire in type 1 diabetes. 36316364 2 20 theme specific 270:277 arg1 ACAs 309:312 ACAs 309:312 ACAs 309:312 Here we report the identification of specific anti-carbohydrate antibodies (ACAs) that are associated with pathogenesis and progression to T1D. 36316364 2 20 theme specific 270:277 arg1 antibodies 297:306 specific anti-carbohydrate antibodies 270:306 specific anti-carbohydrate antibodies (ACAs) that are associated with pathogenesis and progression to T1D 270:374 Here we report the identification of specific anti-carbohydrate antibodies (ACAs) that are associated with pathogenesis and progression to T1D. 36316364 5 21 theme O-linked 741:748 arg1 glycans 750:756 O-linked glycans 741:756 O-linked glycans 741:756 Clusters enriched for aminoglycosides, blood group A and B antigens, glycolipids, ganglio-series, and O-linked glycans are associated with progression to T1D. 36316364 7 22 with model 979:983 arg1 variables 1004:1012 only clinical variables 990:1012 only clinical variables 990:1012 ACAs improve discrimination of T1D status of individuals over a model with only clinical variables and are potential biomarkers for T1D. 36316364 0 23 from repertoire 69:78 arg1 diabetes 90:97 type 1 diabetes 83:97 type 1 diabetes 83:97 Use of a glycomics array to establish the anti-carbohydrate antibody repertoire in type 1 diabetes. 36316364 0 24 theme array 19:23 arg1 Use 0:2 Use 0:2 Use of a glycomics array 0:23 Use of a glycomics array to establish the anti-carbohydrate antibody repertoire in type 1 diabetes. 36316364 3 25 theme circulatory 388:398 arg1 levels 400:405 circulatory levels 388:405 circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112) 388:565 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 7 26 theme individuals 960:970 arg1 status 950:955 T1D status 946:955 T1D status of individuals over a model with only clinical variables 946:1012 ACAs improve discrimination of T1D status of individuals over a model with only clinical variables and are potential biomarkers for T1D. 36316364 3 27 theme ACAs 410:413 arg1 levels 400:405 circulatory levels 388:405 circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112) 388:565 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 3 28 from glycans 427:433 arg1 cohort 550:555 a longitudinal cohort 535:555 a longitudinal cohort (n = 112) 535:565 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 3 28 from glycans 427:433 arg1 cohort 456:461 a cross-sectional cohort 438:461 a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298) 438:518 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 3 28 from glycans 427:433 arg1 n = 112 558:564 n = 112 558:564 n = 112 558:564 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 1 29 theme Type 100:103 arg1 diabetes 107:114 Type 1 diabetes 100:114 Type 1 diabetes (T1D) 100:120 Type 1 diabetes (T1D) is an autoimmune disease, characterized by the presence of autoantibodies to protein and non-protein antigens. 36316364 1 29 theme Type 100:103 arg1 disease 139:145 an autoimmune disease 125:145 an autoimmune disease 125:145 Type 1 diabetes (T1D) is an autoimmune disease, characterized by the presence of autoantibodies to protein and non-protein antigens. 36316364 1 29 theme Type 100:103 arg1 T1D 117:119 T1D 117:119 T1D 117:119 Type 1 diabetes (T1D) is an autoimmune disease, characterized by the presence of autoantibodies to protein and non-protein antigens. 36316364 3 30 theme T1D 466:468 arg1 n = 278 480:486 n = 278 480:486 n = 278 480:486 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 3 30 theme T1D 466:468 arg1 patients 470:477 T1D patients 466:477 T1D patients (n = 278) 466:487 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 7 31 theme status 950:955 arg1 discrimination 928:941 discrimination 928:941 discrimination of T1D status of individuals over a model with only clinical variables 928:1012 ACAs improve discrimination of T1D status of individuals over a model with only clinical variables and are potential biomarkers for T1D. 36316364 5 32 theme A 690:690 arg1 antigens 698:705 blood group A and B antigens 678:705 blood group A and B antigens 678:705 Clusters enriched for aminoglycosides, blood group A and B antigens, glycolipids, ganglio-series, and O-linked glycans are associated with progression to T1D. 36316364 3 33 theme cross-sectional 440:454 arg1 cohort 456:461 a cross-sectional cohort 438:461 a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298) 438:518 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 1 34 theme autoantibodies 181:194 arg1 presence 169:176 the presence 165:176 the presence of autoantibodies to protein and non-protein antigens 165:230 Type 1 diabetes (T1D) is an autoimmune disease, characterized by the presence of autoantibodies to protein and non-protein antigens. 36316364 4 35 dep function 623:630 arg1 class 632:636 class 632:636 glycan function class 616:636 We identify 11 clusters of ACAs associated with glycan function class. 36316364 0 36 theme antibody 60:67 arg1 repertoire 69:78 the anti-carbohydrate antibody repertoire 38:78 the anti-carbohydrate antibody repertoire in type 1 diabetes 38:97 Use of a glycomics array to establish the anti-carbohydrate antibody repertoire in type 1 diabetes. 36316364 3 37 theme longitudinal 537:548 arg1 cohort 550:555 a longitudinal cohort 535:555 a longitudinal cohort (n = 112) 535:565 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 3 37 theme longitudinal 537:548 arg1 n = 112 558:564 n = 112 558:564 n = 112 558:564 We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). 36316364 0 38 theme anti-carbohydrate 42:58 arg1 repertoire 69:78 the anti-carbohydrate antibody repertoire 38:78 the anti-carbohydrate antibody repertoire in type 1 diabetes 38:97 Use of a glycomics array to establish the anti-carbohydrate antibody repertoire in type 1 diabetes. 35906894 0 0 theme glycosylated 98:109 arg1 neuropeptides 111:123 endogenous glycosylated neuropeptides 87:123 endogenous glycosylated neuropeptides 87:123 Enrichment and fragmentation approaches for enhanced detection and characterization of endogenous glycosylated neuropeptides. 35906894 6 1 theme stepped 1045:1051 arg1 dissociation 1096:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 9 2 theme glycosylation 1691:1703 arg1 effects 1680:1686 modulatory effects 1669:1686 modulatory effects of glycosylation on neuropeptides 1669:1720 Both macro- and micro-heterogeneity were observed, demonstrating the chemical diversity of this simple invertebrate, establishing a framework to use crustacean to probe modulatory effects of glycosylation on neuropeptides. 35906894 9 3 theme chemical 1569:1576 arg1 diversity 1578:1586 the chemical diversity 1565:1586 the chemical diversity of this simple invertebrate 1565:1614 Both macro- and micro-heterogeneity were observed, demonstrating the chemical diversity of this simple invertebrate, establishing a framework to use crustacean to probe modulatory effects of glycosylation on neuropeptides. 35906894 8 4 from crustaceans 1390:1400 arg1 database 1348:1355 the database 1344:1355 the database of glycosylated neuropeptides in crustaceans 1344:1400 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 0 5 theme endogenous 87:96 arg1 neuropeptides 111:123 endogenous glycosylated neuropeptides 87:123 endogenous glycosylated neuropeptides 87:123 Enrichment and fragmentation approaches for enhanced detection and characterization of endogenous glycosylated neuropeptides. 35906894 6 6 theme faster 1038:1043 arg1 dissociation 1096:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 7 7 theme more 1235:1238 arg1 glycoforms 1240:1249 36 more glycoforms 1232:1249 36 more glycoforms of known neuropeptides 1232:1272 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 1 8 theme model 196:200 arg1 organism 202:209 a model organism 194:209 a model organism with a well-characterized neuroendocrine system 194:257 Glycosylated neuropeptides were recently discovered in crustaceans, a model organism with a well-characterized neuroendocrine system. 35906894 1 8 theme model 196:200 arg1 crustaceans 181:191 crustaceans 181:191 crustaceans 181:191 Glycosylated neuropeptides were recently discovered in crustaceans, a model organism with a well-characterized neuroendocrine system. 35906894 8 9 from families 1490:1497 arg1 neuropeptides 1455:1467 40 neuropeptides 1452:1467 40 neuropeptides from 10 neuropeptide families 1452:1497 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 8 9 from families 1490:1497 arg1 glycoforms 1438:1447 18 to 136 glycoforms 1428:1447 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families 1428:1497 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 7 10 theme neuropeptides 1260:1272 arg1 glycoforms 1286:1295 11 more glycoforms 1278:1295 11 more glycoforms of nine putative novel neuropeptides 1278:1332 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 7 10 theme neuropeptides 1260:1272 arg1 glycoforms 1240:1249 36 more glycoforms 1232:1249 36 more glycoforms of known neuropeptides 1232:1272 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 2 11 theme unique 346:351 arg1 properties 353:362 the unique properties 342:362 the unique properties of endogenous neuropeptides 342:390 Several workflows exist to characterize enzymatically digested peptides; however, the unique properties of endogenous neuropeptides require methods to be re-evaluated. 35906894 9 12 theme invertebrate 1603:1614 arg1 diversity 1578:1586 the chemical diversity 1565:1586 the chemical diversity of this simple invertebrate 1565:1614 Both macro- and micro-heterogeneity were observed, demonstrating the chemical diversity of this simple invertebrate, establishing a framework to use crustacean to probe modulatory effects of glycosylation on neuropeptides. 35906894 0 13 theme neuropeptides 111:123 arg1 characterization 67:82 characterization 67:82 characterization 67:82 Enrichment and fragmentation approaches for enhanced detection and characterization of endogenous glycosylated neuropeptides. 35906894 0 13 theme neuropeptides 111:123 arg1 detection 53:61 detection 53:61 detection 53:61 Enrichment and fragmentation approaches for enhanced detection and characterization of endogenous glycosylated neuropeptides. 35906894 5 14 theme detected 797:804 arg1 glycoforms 819:828 detected neuropeptide glycoforms 797:828 detected neuropeptide glycoforms 797:828 This modification enabled the number of detected neuropeptide glycoforms to increase almost two-fold, from 18 to 36. 35906894 6 15 theme collision 928:936 arg1 dissociation 938:949 Product ion-triggered electron-transfer/higher-energy collision dissociation 874:949 Product ion-triggered electron-transfer/higher-energy collision dissociation 874:949 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 8 16 dep 136 1434:1436 arg1 to 1431:1432 to 1431:1432 to 1431:1432 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 6 17 theme 25 1134:1135 arg1 detection 1121:1129 detection 1121:1129 detection of 25 1121:1135 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 6 18 link O-linked 1007:1014 arg1 glycoforms 1016:1025 O-linked glycoforms 1007:1025 O-linked glycoforms 1007:1025 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 3 19 gly glycosylated 590:601 arg1 neuropeptides 603:615 glycosylated neuropeptides 590:615 glycosylated neuropeptides 590:615 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 3 20 theme enrichment 508:517 arg1 use 447:449 the use 443:449 the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus 443:638 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 6 21 theme glycoforms 1016:1025 arg1 detection 977:985 the site-specific detection 959:985 the site-specific detection of 55 intact N- and O-linked glycoforms 959:1025 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 0 22 theme enhanced 44:51 arg1 detection 53:61 detection 53:61 detection 53:61 Enrichment and fragmentation approaches for enhanced detection and characterization of endogenous glycosylated neuropeptides. 35906894 6 23 theme ion-triggered 882:894 arg1 dissociation 938:949 Product ion-triggered electron-transfer/higher-energy collision dissociation 874:949 Product ion-triggered electron-transfer/higher-energy collision dissociation 874:949 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 0 24 gly glycosylated 98:109 arg1 neuropeptides 111:123 endogenous glycosylated neuropeptides 87:123 endogenous glycosylated neuropeptides 87:123 Enrichment and fragmentation approaches for enhanced detection and characterization of endogenous glycosylated neuropeptides. 35906894 4 25 theme peptide 740:746 arg1 samples 748:754 endogenous peptide samples 729:754 endogenous peptide samples 729:754 During the evaluation of HILIC, we observed the necessity of a less aqueous solvent for endogenous peptide samples. 35906894 6 26 theme O-linked 1007:1014 arg1 glycoforms 1016:1025 O-linked glycoforms 1007:1025 O-linked glycoforms 1007:1025 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 5 27 dep 36 870:871 arg1 to 867:868 to 867:868 to 867:868 This modification enabled the number of detected neuropeptide glycoforms to increase almost two-fold, from 18 to 36. 35906894 6 28 theme Product 874:880 arg1 dissociation 938:949 Product ion-triggered electron-transfer/higher-energy collision dissociation 874:949 Product ion-triggered electron-transfer/higher-energy collision dissociation 874:949 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 2 29 theme neuropeptides 378:390 arg1 properties 353:362 the unique properties 342:362 the unique properties of endogenous neuropeptides 342:390 Several workflows exist to characterize enzymatically digested peptides; however, the unique properties of endogenous neuropeptides require methods to be re-evaluated. 35906894 7 30 gly glycoforms 1240:1249 arg1 neuropeptides 1320:1332 nine putative novel neuropeptides 1300:1332 nine putative novel neuropeptides 1300:1332 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 7 30 gly glycoforms 1240:1249 arg1 neuropeptides 1260:1272 known neuropeptides 1254:1272 known neuropeptides 1254:1272 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 3 31 theme hydrophilic 454:464 arg1 HILIC 501:505 HILIC 501:505 HILIC 501:505 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 3 31 theme hydrophilic 454:464 arg1 chromatography 485:498 hydrophilic interaction liquid chromatography 454:498 hydrophilic interaction liquid chromatography (HILIC) enrichment 454:517 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 7 32 theme glycoforms 1240:1249 arg1 characterization 1212:1227 the characterization 1208:1227 the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides 1208:1332 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 2 33 theme endogenous 367:376 arg1 neuropeptides 378:390 endogenous neuropeptides 367:390 endogenous neuropeptides 367:390 Several workflows exist to characterize enzymatically digested peptides; however, the unique properties of endogenous neuropeptides require methods to be re-evaluated. 35906894 1 34 theme well-characterized 218:235 arg1 system 252:257 a well-characterized neuroendocrine system 216:257 a well-characterized neuroendocrine system 216:257 Glycosylated neuropeptides were recently discovered in crustaceans, a model organism with a well-characterized neuroendocrine system. 35906894 7 35 theme novel 1314:1318 arg1 neuropeptides 1320:1332 nine putative novel neuropeptides 1300:1332 nine putative novel neuropeptides 1300:1332 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 3 36 from expression 576:585 arg1 sapidus 632:638 Callinectes sapidus 620:638 Callinectes sapidus 620:638 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 1 37 theme Glycosylated 126:137 arg1 neuropeptides 139:151 Glycosylated neuropeptides 126:151 Glycosylated neuropeptides 126:151 Glycosylated neuropeptides were recently discovered in crustaceans, a model organism with a well-characterized neuroendocrine system. 35906894 7 38 theme known 1254:1258 arg1 neuropeptides 1260:1272 known neuropeptides 1254:1272 known neuropeptides 1254:1272 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 3 39 theme methods 547:553 arg1 use 447:449 the use 443:449 the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus 443:638 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 7 40 theme neuropeptides 1320:1332 arg1 glycoforms 1286:1295 11 more glycoforms 1278:1295 11 more glycoforms of nine putative novel neuropeptides 1278:1332 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 7 40 theme neuropeptides 1320:1332 arg1 glycoforms 1240:1249 36 more glycoforms 1232:1249 36 more glycoforms of known neuropeptides 1232:1272 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 4 41 theme HILIC 666:670 arg1 evaluation 652:661 the evaluation 648:661 the evaluation of HILIC 648:670 During the evaluation of HILIC, we observed the necessity of a less aqueous solvent for endogenous peptide samples. 35906894 3 42 theme Callinectes 620:630 arg1 sapidus 632:638 Callinectes sapidus 620:638 Callinectes sapidus 620:638 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 3 43 theme glycosylated 590:601 arg1 neuropeptides 603:615 glycosylated neuropeptides 590:615 glycosylated neuropeptides 590:615 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 8 44 from database 1348:1355 arg1 crustaceans 1390:1400 crustaceans 1390:1400 crustaceans 1390:1400 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 4 45 theme aqueous 709:715 arg1 solvent 717:723 a less aqueous solvent 702:723 a less aqueous solvent 702:723 During the evaluation of HILIC, we observed the necessity of a less aqueous solvent for endogenous peptide samples. 35906894 3 46 theme chromatography 485:498 arg1 enrichment 508:517 hydrophilic interaction liquid chromatography (HILIC) enrichment 454:517 hydrophilic interaction liquid chromatography (HILIC) enrichment 454:517 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 5 47 theme neuropeptide 806:817 arg1 glycoforms 819:828 detected neuropeptide glycoforms 797:828 detected neuropeptide glycoforms 797:828 This modification enabled the number of detected neuropeptide glycoforms to increase almost two-fold, from 18 to 36. 35906894 4 48 theme endogenous 729:738 arg1 samples 748:754 endogenous peptide samples 729:754 endogenous peptide samples 729:754 During the evaluation of HILIC, we observed the necessity of a less aqueous solvent for endogenous peptide samples. 35906894 3 49 theme different 523:531 arg1 methods 547:553 different fragmentation methods 523:553 different fragmentation methods 523:553 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 7 50 theme putative 1305:1312 arg1 neuropeptides 1320:1332 nine putative novel neuropeptides 1300:1332 nine putative novel neuropeptides 1300:1332 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 5 51 theme glycoforms 819:828 arg1 number 787:792 the number 783:792 the number of detected neuropeptide glycoforms to increase almost two-fold 783:856 This modification enabled the number of detected neuropeptide glycoforms to increase almost two-fold, from 18 to 36. 35906894 6 52 theme intact 993:998 arg1 N- 1000:1001 55 intact N- 990:1001 55 intact N- 990:1001 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 9 53 from effects 1680:1686 arg1 neuropeptides 1708:1720 neuropeptides 1708:1720 neuropeptides 1708:1720 Both macro- and micro-heterogeneity were observed, demonstrating the chemical diversity of this simple invertebrate, establishing a framework to use crustacean to probe modulatory effects of glycosylation on neuropeptides. 35906894 3 54 theme fragmentation 533:545 arg1 methods 547:553 different fragmentation methods 523:553 different fragmentation methods 523:553 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 3 55 theme interaction 466:476 arg1 HILIC 501:505 HILIC 501:505 HILIC 501:505 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 3 55 theme interaction 466:476 arg1 chromatography 485:498 hydrophilic interaction liquid chromatography 454:498 hydrophilic interaction liquid chromatography (HILIC) enrichment 454:517 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 6 56 theme collisional 1084:1094 arg1 dissociation 1096:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 8 57 theme neuropeptides 1373:1385 arg1 database 1348:1355 the database 1344:1355 the database of glycosylated neuropeptides in crustaceans 1344:1400 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 8 58 from neuropeptides 1373:1385 arg1 crustaceans 1390:1400 crustaceans 1390:1400 crustaceans 1390:1400 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 9 59 theme modulatory 1669:1678 arg1 effects 1680:1686 modulatory effects 1669:1686 modulatory effects of glycosylation on neuropeptides 1669:1720 Both macro- and micro-heterogeneity were observed, demonstrating the chemical diversity of this simple invertebrate, establishing a framework to use crustacean to probe modulatory effects of glycosylation on neuropeptides. 35906894 3 60 theme liquid 478:483 arg1 HILIC 501:505 HILIC 501:505 HILIC 501:505 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 3 60 theme liquid 478:483 arg1 chromatography 485:498 hydrophilic interaction liquid chromatography 454:498 hydrophilic interaction liquid chromatography (HILIC) enrichment 454:517 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 6 61 theme higher-energy 1070:1082 arg1 dissociation 1096:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 2 62 theme Several 260:266 arg1 workflows 268:276 Several workflows 260:276 Several workflows 260:276 Several workflows exist to characterize enzymatically digested peptides; however, the unique properties of endogenous neuropeptides require methods to be re-evaluated. 35906894 7 63 gly glycoforms 1286:1295 arg1 neuropeptides 1320:1332 nine putative novel neuropeptides 1300:1332 nine putative novel neuropeptides 1300:1332 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 7 63 gly glycoforms 1286:1295 arg1 neuropeptides 1260:1272 known neuropeptides 1254:1272 known neuropeptides 1254:1272 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 7 64 theme more 1281:1284 arg1 glycoforms 1286:1295 11 more glycoforms 1278:1295 11 more glycoforms of nine putative novel neuropeptides 1278:1332 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 6 65 theme energy 1063:1068 arg1 dissociation 1096:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 1 66 with organism 202:209 arg1 system 252:257 a well-characterized neuroendocrine system 216:257 a well-characterized neuroendocrine system 216:257 Glycosylated neuropeptides were recently discovered in crustaceans, a model organism with a well-characterized neuroendocrine system. 35906894 8 67 gly glycosylated 1360:1371 arg1 neuropeptides 1373:1385 glycosylated neuropeptides 1360:1385 glycosylated neuropeptides in crustaceans 1360:1400 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 5 68 gly glycoforms 819:828 arg1 neuropeptide 806:817 detected neuropeptide glycoforms 797:828 detected neuropeptide glycoforms 797:828 This modification enabled the number of detected neuropeptide glycoforms to increase almost two-fold, from 18 to 36. 35906894 7 69 theme neuronal 1183:1190 arg1 tissues 1192:1198 five neuronal tissues 1178:1198 five neuronal tissues 1178:1198 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 6 70 theme site-specific 963:975 arg1 detection 977:985 the site-specific detection 959:985 the site-specific detection of 55 intact N- and O-linked glycoforms 959:1025 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 8 71 theme neuropeptide 1477:1488 arg1 families 1490:1497 10 neuropeptide families 1474:1497 10 neuropeptide families 1474:1497 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 8 72 from glycoforms 1438:1447 arg1 families 1490:1497 10 neuropeptide families 1474:1497 10 neuropeptide families 1474:1497 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 8 73 theme neuropeptides 1455:1467 arg1 glycoforms 1438:1447 18 to 136 glycoforms 1428:1447 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families 1428:1497 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 6 74 theme electron-transfer/higher-energy 896:926 arg1 dissociation 938:949 Product ion-triggered electron-transfer/higher-energy collision dissociation 874:949 Product ion-triggered electron-transfer/higher-energy collision dissociation 874:949 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 8 75 theme glycosylated 1360:1371 arg1 neuropeptides 1373:1385 glycosylated neuropeptides 1360:1385 glycosylated neuropeptides in crustaceans 1360:1400 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 6 76 theme N- 1000:1001 arg1 detection 977:985 the site-specific detection 959:985 the site-specific detection of 55 intact N- and O-linked glycoforms 959:1025 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 8 77 gly glycoforms 1438:1447 arg1 neuropeptides 1455:1467 40 neuropeptides 1452:1467 40 neuropeptides from 10 neuropeptide families 1452:1497 Overall, the database of glycosylated neuropeptides in crustaceans was largely expanded from 18 to 136 glycoforms of 40 neuropeptides from 10 neuropeptide families. 35906894 2 78 theme digested 314:321 arg1 peptides 323:330 enzymatically digested peptides 300:330 enzymatically digested peptides 300:330 Several workflows exist to characterize enzymatically digested peptides; however, the unique properties of endogenous neuropeptides require methods to be re-evaluated. 35906894 1 79 theme neuroendocrine 237:250 arg1 system 252:257 a well-characterized neuroendocrine system 216:257 a well-characterized neuroendocrine system 216:257 Glycosylated neuropeptides were recently discovered in crustaceans, a model organism with a well-characterized neuroendocrine system. 35906894 3 80 theme neuropeptides 603:615 arg1 expression 576:585 the expression 572:585 the expression of glycosylated neuropeptides in Callinectes sapidus 572:638 We investigate the use of hydrophilic interaction liquid chromatography (HILIC) enrichment and different fragmentation methods to further probe the expression of glycosylated neuropeptides in Callinectes sapidus. 35906894 7 81 theme glycoforms 1286:1295 arg1 characterization 1212:1227 the characterization 1208:1227 the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides 1208:1332 Additionally, applying this workflow to five neuronal tissues enabled the characterization of 36 more glycoforms of known neuropeptides and 11 more glycoforms of nine putative novel neuropeptides. 35906894 6 82 theme collision 1053:1061 arg1 dissociation 1096:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 the faster stepped collision energy higher-energy collisional dissociation 1034:1107 Product ion-triggered electron-transfer/higher-energy collision dissociation enabled the site-specific detection of 55 intact N- and O-linked glycoforms, while the faster stepped collision energy higher-energy collisional dissociation resulted in detection of 25. 35906894 4 83 theme solvent 717:723 arg1 necessity 689:697 the necessity 685:697 the necessity of a less aqueous solvent for endogenous peptide samples 685:754 During the evaluation of HILIC, we observed the necessity of a less aqueous solvent for endogenous peptide samples. 36366419 5 0 theme RSV 681:683 arg1 genes 687:691 Complete RSV F genes 672:691 Complete RSV F genes 672:691 Complete RSV F genes were amplified for next-generation sequencing. 36366419 12 1 theme S275F 1297:1301 arg1 mutation 1303:1310 The S275F mutation 1293:1310 The S275F mutation 1293:1310 The S275F mutation was seen in a single South African strain. 36366419 10 2 theme gene 1144:1147 arg1 sequences 1149:1157 F gene sequences 1142:1157 F gene sequences 1142:1157 About 74.2% (23/31) of F gene sequences cluster with other African NA1/ON1 genotypes. 36366419 0 3 theme RSV 73:75 arg1 Disease 77:83 RSV Disease 73:83 RSV Disease 73:83 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020. 36366419 13 4 theme proteins 1431:1438 arg1 proteins 1431:1438 RSV-A F proteins 1423:1438 RSV-A F proteins described in this study 1423:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 4 theme proteins 1431:1438 arg1 8/31 1414:1417 8/31 1414:1417 8/31 1414:1417 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 4 theme proteins 1431:1438 arg1 % 1411:1411 25.8% 1407:1411 25.8% (8/31) of RSV-A F proteins described in this study 1407:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 14 5 theme first 1473:1477 arg1 time 1479:1482 the first time 1469:1482 the first time 1469:1482 For the first time, we detected the rare S275F mutation that is associated with palivizumab resistance. 36366419 11 6 theme antigenic 1208:1216 arg1 site 1218:1221 antigenic site I 1208:1223 antigenic site I 1208:1223 At antigenic site I, the V384I mutation was replaced by V384T in South African strains. 36366419 10 7 theme NA1/ON1 1186:1192 arg1 genotypes 1194:1202 other African NA1/ON1 genotypes 1172:1202 other African NA1/ON1 genotypes 1172:1202 About 74.2% (23/31) of F gene sequences cluster with other African NA1/ON1 genotypes. 36366419 0 8 dep 2020 94:97 arg1 to 91:92 to 91:92 to 91:92 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020. 36366419 7 9 theme overall 796:802 arg1 prevalence 804:813 The overall prevalence 792:813 The overall prevalence of RSV 792:820 The overall prevalence of RSV was 5.8% (101/1734). 36366419 7 9 theme overall 796:802 arg1 % 829:829 5.8% 826:829 5.8% (101/1734) 826:840 The overall prevalence of RSV was 5.8% (101/1734). 36366419 10 10 theme African 1178:1184 arg1 genotypes 1194:1202 other African NA1/ON1 genotypes 1172:1202 other African NA1/ON1 genotypes 1172:1202 About 74.2% (23/31) of F gene sequences cluster with other African NA1/ON1 genotypes. 36366419 13 11 theme glycosylation 1373:1385 arg1 present 1396:1402 present 1396:1402 present 1396:1402 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 11 theme glycosylation 1373:1385 arg1 site 1387:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 4 12 theme respiratory 494:504 arg1 samples 506:512 respiratory samples 494:512 respiratory samples 494:512 Patients of all ages, from whom respiratory samples were submitted to the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa during 2019 to 2020, were included. 36366419 5 13 theme F 685:685 arg1 genes 687:691 Complete RSV F genes 672:691 Complete RSV F genes 672:691 Complete RSV F genes were amplified for next-generation sequencing. 36366419 8 14 theme RSV 937:939 arg1 protein 943:949 RSV F protein 937:949 the RSV F protein gene 933:954 Among 101 RSV positive samples only 69.3% (70/101) were available for characterization of the RSV F protein gene. 36366419 0 15 with Patients 59:66 arg1 Disease 77:83 RSV Disease 73:83 RSV Disease 73:83 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020. 36366419 11 16 theme V384I 1230:1234 arg1 mutation 1236:1243 the V384I mutation 1226:1243 the V384I mutation 1226:1243 At antigenic site I, the V384I mutation was replaced by V384T in South African strains. 36366419 13 17 link N-linked 1364:1371 arg1 present 1396:1402 present 1396:1402 present 1396:1402 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 17 link N-linked 1364:1371 arg1 site 1387:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 18 theme F 1429:1429 arg1 proteins 1431:1438 RSV-A F proteins 1423:1438 RSV-A F proteins described in this study 1423:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 19 from % 1411:1411 arg1 present 1396:1402 present 1396:1402 present 1396:1402 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 19 from % 1411:1411 arg1 site 1387:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 2 20 theme antigenic 322:330 arg1 sites 332:336 antigenic sites 322:336 antigenic sites 322:336 The fusion (F) protein is highly conserved; however, variability within antigenic sites has been reported. 36366419 5 21 theme next-generation 712:726 arg1 sequencing 728:737 next-generation sequencing 712:737 next-generation sequencing 712:737 Complete RSV F genes were amplified for next-generation sequencing. 36366419 4 22 theme ages 478:481 arg1 Patients 462:469 Patients 462:469 Patients 462:469 Patients of all ages, from whom respiratory samples were submitted to the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa during 2019 to 2020, were included. 36366419 8 23 theme protein 943:949 arg1 gene 951:954 the RSV F protein gene 933:954 the RSV F protein gene 933:954 Among 101 RSV positive samples only 69.3% (70/101) were available for characterization of the RSV F protein gene. 36366419 14 24 theme palivizumab 1545:1555 arg1 resistance 1557:1566 palivizumab resistance 1545:1566 palivizumab resistance 1545:1566 For the first time, we detected the rare S275F mutation that is associated with palivizumab resistance. 36366419 2 25 theme F 262:262 arg1 protein 265:271 The fusion (F) protein 250:271 The fusion (F) protein 250:271 The fusion (F) protein is highly conserved; however, variability within antigenic sites has been reported. 36366419 13 26 gly glycosylation 1373:1385 arg1 proteins 1431:1438 RSV-A F proteins 1423:1438 RSV-A F proteins described in this study 1423:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 26 gly glycosylation 1373:1385 arg1 8/31 1414:1417 8/31 1414:1417 8/31 1414:1417 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 26 gly glycosylation 1373:1385 arg2 site 1387:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 26 gly glycosylation 1373:1385 arg1 % 1411:1411 25.8% 1407:1411 25.8% (8/31) of RSV-A F proteins described in this study 1407:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 26 gly glycosylation 1373:1385 arg2 present 1396:1402 present 1396:1402 present 1396:1402 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 8 27 theme F 941:941 arg1 protein 943:949 RSV F protein 937:949 the RSV F protein gene 933:954 Among 101 RSV positive samples only 69.3% (70/101) were available for characterization of the RSV F protein gene. 36366419 13 28 theme RSV-A 1423:1427 arg1 proteins 1431:1438 RSV-A F proteins 1423:1438 RSV-A F proteins described in this study 1423:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 0 29 theme Fusion 24:29 arg1 Proteins 31:38 RSV Fusion Proteins 20:38 RSV Fusion Proteins 20:38 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020. 36366419 1 30 theme G 242:242 arg1 gene 244:247 the G gene 238:247 the G gene 238:247 Respiratory syncytial virus (RSV) is classified into RSV-A and RSV-B, which are further classified into genotypes based on variability in the G gene. 36366419 1 31 from variability 223:233 arg1 gene 244:247 the G gene 238:247 the G gene 238:247 Respiratory syncytial virus (RSV) is classified into RSV-A and RSV-B, which are further classified into genotypes based on variability in the G gene. 36366419 10 32 theme other 1172:1176 arg1 genotypes 1194:1202 other African NA1/ON1 genotypes 1172:1202 other African NA1/ON1 genotypes 1172:1202 About 74.2% (23/31) of F gene sequences cluster with other African NA1/ON1 genotypes. 36366419 2 33 theme fusion 254:259 arg1 protein 265:271 The fusion (F) protein 250:271 The fusion (F) protein 250:271 The fusion (F) protein is highly conserved; however, variability within antigenic sites has been reported. 36366419 4 34 theme Health 545:550 arg1 Service 563:569 the National Health Laboratory Service 532:569 the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa 532:634 Patients of all ages, from whom respiratory samples were submitted to the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa during 2019 to 2020, were included. 36366419 0 35 theme RSV 20:22 arg1 Proteins 31:38 RSV Fusion Proteins 20:38 RSV Fusion Proteins 20:38 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020. 36366419 11 36 theme African 1276:1282 arg1 strains 1284:1290 South African strains 1270:1290 South African strains 1270:1290 At antigenic site I, the V384I mutation was replaced by V384T in South African strains. 36366419 8 37 theme gene 951:954 arg1 characterization 913:928 characterization 913:928 characterization of the RSV F protein gene 913:954 Among 101 RSV positive samples only 69.3% (70/101) were available for characterization of the RSV F protein gene. 36366419 13 38 theme N120 1359:1362 arg1 present 1396:1402 present 1396:1402 present 1396:1402 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 38 theme N120 1359:1362 arg1 site 1387:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 9 39 theme F 982:982 arg1 characterisation 989:1004 F gene characterisation 982:1004 F gene characterisation 982:1004 Among cases included for F gene characterisation, viral co-infections were observed in 50% (35/70) and 25.7% (18/70) were admitted to intensive care units (ICU). 36366419 4 40 theme National 536:543 arg1 Service 563:569 the National Health Laboratory Service 532:569 the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa 532:634 Patients of all ages, from whom respiratory samples were submitted to the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa during 2019 to 2020, were included. 36366419 3 41 dep 2020 456:459 arg1 to 453:454 to 453:454 to 453:454 This study aimed to characterise F proteins from RSV strains detected in South Africa from 2019 to 2020. 36366419 9 42 theme gene 984:987 arg1 characterisation 989:1004 F gene characterisation 982:1004 F gene characterisation 982:1004 Among cases included for F gene characterisation, viral co-infections were observed in 50% (35/70) and 25.7% (18/70) were admitted to intensive care units (ICU). 36366419 0 43 theme Proteins 31:38 arg1 Characterisation 0:15 Characterisation 0:15 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease 0:83 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020. 36366419 0 43 theme Proteins 31:38 arg1 2020 94:97 2020 94:97 2020 94:97 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020. 36366419 6 44 theme phylogenetic 769:780 arg1 analysis 782:789 phylogenetic analysis 769:789 phylogenetic analysis 769:789 MEGA X software was used for phylogenetic analysis. 36366419 13 45 from present 1396:1402 arg1 proteins 1431:1438 RSV-A F proteins 1423:1438 RSV-A F proteins described in this study 1423:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 45 from present 1396:1402 arg1 8/31 1414:1417 8/31 1414:1417 8/31 1414:1417 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 45 from present 1396:1402 arg1 % 1411:1411 25.8% 1407:1411 25.8% (8/31) of RSV-A F proteins described in this study 1407:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 10 46 theme F 1142:1142 arg1 sequences 1149:1157 F gene sequences 1142:1157 F gene sequences 1142:1157 About 74.2% (23/31) of F gene sequences cluster with other African NA1/ON1 genotypes. 36366419 4 47 theme Laboratory 552:561 arg1 Service 563:569 the National Health Laboratory Service 532:569 the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa 532:634 Patients of all ages, from whom respiratory samples were submitted to the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa during 2019 to 2020, were included. 36366419 0 48 theme African 51:57 arg1 Patients 59:66 South African Patients 45:66 South African Patients with RSV Disease 45:83 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020. 36366419 0 49 from Patients 59:66 arg1 Characterisation 0:15 Characterisation 0:15 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease 0:83 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020. 36366419 0 49 from Patients 59:66 arg1 2020 94:97 2020 94:97 2020 94:97 Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020. 36366419 14 50 theme S275F 1506:1510 arg1 mutation 1512:1519 the rare S275F mutation 1497:1519 the rare S275F mutation that is associated with palivizumab resistance 1497:1566 For the first time, we detected the rare S275F mutation that is associated with palivizumab resistance. 36366419 9 51 theme viral 1007:1011 arg1 co-infections 1013:1025 viral co-infections 1007:1025 viral co-infections 1007:1025 Among cases included for F gene characterisation, viral co-infections were observed in 50% (35/70) and 25.7% (18/70) were admitted to intensive care units (ICU). 36366419 1 52 theme Respiratory 100:110 arg1 RSV 129:131 RSV 129:131 RSV 129:131 Respiratory syncytial virus (RSV) is classified into RSV-A and RSV-B, which are further classified into genotypes based on variability in the G gene. 36366419 1 52 theme Respiratory 100:110 arg1 virus 122:126 Respiratory syncytial virus 100:126 Respiratory syncytial virus (RSV) 100:132 Respiratory syncytial virus (RSV) is classified into RSV-A and RSV-B, which are further classified into genotypes based on variability in the G gene. 36366419 13 53 located present 1396:1402 arg2 site 1387:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 53 located present 1396:1402 arg1 proteins 1431:1438 RSV-A F proteins 1423:1438 RSV-A F proteins described in this study 1423:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 53 located present 1396:1402 arg1 % 1411:1411 25.8% 1407:1411 25.8% (8/31) of RSV-A F proteins described in this study 1407:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 53 located present 1396:1402 arg2 present 1396:1402 present 1396:1402 present 1396:1402 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 53 located present 1396:1402 arg1 8/31 1414:1417 8/31 1414:1417 8/31 1414:1417 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 9 54 theme intensive 1091:1099 arg1 ICU 1113:1115 ICU 1113:1115 ICU 1113:1115 Among cases included for F gene characterisation, viral co-infections were observed in 50% (35/70) and 25.7% (18/70) were admitted to intensive care units (ICU). 36366419 9 54 theme intensive 1091:1099 arg1 units 1106:1110 intensive care units 1091:1110 intensive care units (ICU) 1091:1116 Among cases included for F gene characterisation, viral co-infections were observed in 50% (35/70) and 25.7% (18/70) were admitted to intensive care units (ICU). 36366419 1 55 theme syncytial 112:120 arg1 RSV 129:131 RSV 129:131 RSV 129:131 Respiratory syncytial virus (RSV) is classified into RSV-A and RSV-B, which are further classified into genotypes based on variability in the G gene. 36366419 1 55 theme syncytial 112:120 arg1 virus 122:126 Respiratory syncytial virus 100:126 Respiratory syncytial virus (RSV) 100:132 Respiratory syncytial virus (RSV) is classified into RSV-A and RSV-B, which are further classified into genotypes based on variability in the G gene. 36366419 10 56 theme sequences 1149:1157 arg1 sequences 1149:1157 F gene sequences 1142:1157 F gene sequences 1142:1157 About 74.2% (23/31) of F gene sequences cluster with other African NA1/ON1 genotypes. 36366419 10 56 theme sequences 1149:1157 arg1 23/31 1132:1136 23/31 1132:1136 23/31 1132:1136 About 74.2% (23/31) of F gene sequences cluster with other African NA1/ON1 genotypes. 36366419 10 56 theme sequences 1149:1157 arg1 % 1129:1129 About 74.2% 1119:1129 About 74.2% (23/31) of F gene sequences 1119:1157 About 74.2% (23/31) of F gene sequences cluster with other African NA1/ON1 genotypes. 36366419 9 57 theme care 1101:1104 arg1 ICU 1113:1115 ICU 1113:1115 ICU 1113:1115 Among cases included for F gene characterisation, viral co-infections were observed in 50% (35/70) and 25.7% (18/70) were admitted to intensive care units (ICU). 36366419 9 57 theme care 1101:1104 arg1 units 1106:1110 intensive care units 1091:1110 intensive care units (ICU) 1091:1116 Among cases included for F gene characterisation, viral co-infections were observed in 50% (35/70) and 25.7% (18/70) were admitted to intensive care units (ICU). 36366419 13 58 theme N-linked 1364:1371 arg1 present 1396:1402 present 1396:1402 present 1396:1402 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 58 theme N-linked 1364:1371 arg1 site 1387:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 4 59 dep 2020 651:654 arg1 to 648:649 to 648:649 to 648:649 Patients of all ages, from whom respiratory samples were submitted to the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa during 2019 to 2020, were included. 36366419 7 60 theme RSV 818:820 arg1 prevalence 804:813 The overall prevalence 792:813 The overall prevalence of RSV 792:820 The overall prevalence of RSV was 5.8% (101/1734). 36366419 7 60 theme RSV 818:820 arg1 % 829:829 5.8% 826:829 5.8% (101/1734) 826:840 The overall prevalence of RSV was 5.8% (101/1734). 36366419 3 61 theme RSV 406:408 arg1 strains 410:416 RSV strains 406:416 RSV strains detected in South Africa from 2019 to 2020 406:459 This study aimed to characterise F proteins from RSV strains detected in South Africa from 2019 to 2020. 36366419 3 62 theme F 390:390 arg1 proteins 392:399 F proteins 390:399 F proteins 390:399 This study aimed to characterise F proteins from RSV strains detected in South Africa from 2019 to 2020. 36366419 3 63 located detected 418:425 arg1 Africa 436:441 Africa 436:441 Africa 436:441 This study aimed to characterise F proteins from RSV strains detected in South Africa from 2019 to 2020. 36366419 3 63 located detected 418:425 arg2 strains 410:416 RSV strains 406:416 RSV strains detected in South Africa from 2019 to 2020 406:459 This study aimed to characterise F proteins from RSV strains detected in South Africa from 2019 to 2020. 36366419 4 64 from Africa 629:634 arg1 Service 563:569 the National Health Laboratory Service 532:569 the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa 532:634 Patients of all ages, from whom respiratory samples were submitted to the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa during 2019 to 2020, were included. 36366419 12 65 theme African 1339:1345 arg1 strain 1347:1352 a single South African strain 1324:1352 a single South African strain 1324:1352 The S275F mutation was seen in a single South African strain. 36366419 5 66 theme Complete 672:679 arg1 genes 687:691 Complete RSV F genes 672:691 Complete RSV F genes 672:691 Complete RSV F genes were amplified for next-generation sequencing. 36366419 6 67 used used 760:763 arg2 MEGA 740:743 MEGA 740:743 MEGA 740:743 MEGA X software was used for phylogenetic analysis. 36366419 6 67 used used 760:763 arg2 software 747:754 software 747:754 software 747:754 MEGA X software was used for phylogenetic analysis. 36366419 8 68 theme positive 857:864 arg1 samples 866:872 101 RSV positive samples 849:872 101 RSV positive samples 849:872 Among 101 RSV positive samples only 69.3% (70/101) were available for characterization of the RSV F protein gene. 36366419 13 69 attach present 1396:1402 arg1 proteins 1431:1438 RSV-A F proteins 1423:1438 RSV-A F proteins described in this study 1423:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 69 attach present 1396:1402 arg1 8/31 1414:1417 8/31 1414:1417 8/31 1414:1417 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 69 attach present 1396:1402 arg2 site 1387:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site 1355:1390 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 69 attach present 1396:1402 arg1 % 1411:1411 25.8% 1407:1411 25.8% (8/31) of RSV-A F proteins described in this study 1407:1462 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 13 69 attach present 1396:1402 arg2 present 1396:1402 present 1396:1402 present 1396:1402 The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. 36366419 14 70 theme rare 1501:1504 arg1 mutation 1512:1519 the rare S275F mutation 1497:1519 the rare S275F mutation that is associated with palivizumab resistance 1497:1566 For the first time, we detected the rare S275F mutation that is associated with palivizumab resistance. 35262531 9 0 with combination 1497:1507 arg1 regimen 1538:1544 an optimized background regimen 1514:1544 an optimized background regimen 1514:1544 These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen. 35262531 6 1 from sites 1148:1152 arg1 loop 1160:1163 V5 loop 1157:1163 V5 loop 1157:1163 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 4 2 theme reduced 834:840 arg1 susceptibility 842:855 reduced susceptibility 834:855 reduced susceptibility 834:855 Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility. 35262531 6 3 gly glycosylation 1134:1146 arg2 sites 1148:1152 potential N-linked glycosylation sites 1115:1152 potential N-linked glycosylation sites in V5 loop 1115:1163 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 3 4 theme phenotypic 506:515 arg1 susceptibility 517:530 phenotypic susceptibility 506:530 phenotypic susceptibility of 16 HIV-2 primary isolates 506:559 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 9 5 theme optimized 1517:1525 arg1 regimen 1538:1544 an optimized background regimen 1514:1544 an optimized background regimen 1514:1544 These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen. 35262531 6 6 theme V5 1157:1158 arg1 loop 1160:1163 V5 loop 1157:1163 V5 loop 1157:1163 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 7 7 theme reference 1287:1295 arg1 strain 1297:1302 the HIV-2 reference strain 1277:1302 the HIV-2 reference strain 1277:1302 However, both presented shorter V1 and V2 loops than the HIV-2 reference strain. 35262531 6 8 theme sites 1148:1152 arg1 loss 1107:1110 a loss 1105:1110 a loss of potential N-linked glycosylation sites in V5 loop 1105:1163 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 3 9 theme HIV-2 538:542 arg1 isolates 552:559 16 HIV-2 primary isolates 535:559 16 HIV-2 primary isolates 535:559 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 6 10 with strains 1187:1193 arg1 susceptibility 1208:1221 reduced susceptibility 1200:1221 reduced susceptibility 1200:1221 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 1 11 theme rapid 174:178 arg1 selection 180:188 the rapid selection 170:188 the rapid selection of mutations at time of virological failure 170:232 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 1 12 from number 246:251 arg1 time 206:209 time 206:209 time of virological failure 206:232 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 5 13 theme median 1001:1006 arg1 MPI 1008:1010 a median MPI 999:1010 a median MPI of 93% 999:1017 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 5 14 theme viral 887:891 arg1 replication 893:903 viral replication 887:903 viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), 887:993 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 8 15 theme HIV-2 1336:1340 arg1 replication 1342:1352 HIV-2 replication 1336:1352 HIV-2 replication 1336:1352 CONCLUSION Ibalizumab inhibits HIV-2 replication, with IC 50 and MPI in the range of those reported for HIV-1. 35262531 6 16 theme glycosylation 1134:1146 arg1 sites 1148:1152 potential N-linked glycosylation sites 1115:1152 potential N-linked glycosylation sites in V5 loop 1115:1163 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 6 17 theme potential 1115:1123 arg1 sites 1148:1152 potential N-linked glycosylation sites 1115:1152 potential N-linked glycosylation sites in V5 loop 1115:1163 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 9 18 dep in 1422:1423 arg1 vitro 1425:1429 vitro 1425:1429 vitro 1425:1429 These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen. 35262531 3 19 theme isolates 552:559 arg1 susceptibility 517:530 phenotypic susceptibility 506:530 phenotypic susceptibility of 16 HIV-2 primary isolates 506:559 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 1 20 from selection 180:188 arg1 time 206:209 time 206:209 time of virological failure 206:232 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 1 21 theme multidrug-resistant 111:129 arg1 HIV-2 131:135 multidrug-resistant HIV-2 111:135 multidrug-resistant HIV-2 111:135 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 7 22 theme shorter 1248:1254 arg1 loops 1266:1270 shorter V1 and V2 loops 1248:1270 shorter V1 and V2 loops 1248:1270 However, both presented shorter V1 and V2 loops than the HIV-2 reference strain. 35262531 1 23 theme OBJECTIVE 88:96 arg1 issue 152:156 an emerging issue 140:156 an emerging issue 140:156 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 1 23 theme OBJECTIVE 88:96 arg1 Treatment 98:106 OBJECTIVE Treatment 88:106 OBJECTIVE Treatment of multidrug-resistant HIV-2 88:135 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 6 24 theme HIV-1 1181:1185 arg1 strains 1187:1193 HIV-1 strains 1181:1193 HIV-1 strains with reduced susceptibility 1181:1221 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 3 25 theme version 591:597 arg1 assay 653:657 a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay 580:657 a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay 580:657 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 1 26 theme low 242:244 arg1 number 246:251 the low number 238:251 the low number of antiretrovirals active on HIV-2 238:286 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 1 27 theme emerging 143:150 arg1 issue 152:156 an emerging issue 140:156 an emerging issue 140:156 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 1 27 theme emerging 143:150 arg1 Treatment 98:106 OBJECTIVE Treatment 88:106 OBJECTIVE Treatment of multidrug-resistant HIV-2 88:135 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 9 28 with patients 1469:1476 arg1 HIV-2 1487:1491 MDR HIV-2 1483:1491 MDR HIV-2 1483:1491 These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen. 35262531 0 29 theme HIV-2 63:67 arg1 isolates 78:85 group A and group B HIV-2 clinical isolates 43:85 group A and group B HIV-2 clinical isolates 43:85 Ibalizumab shows in-vitro activity against group A and group B HIV-2 clinical isolates. 35262531 2 30 theme HIV-1 482:486 arg1 treatment 465:473 the treatment 461:473 the treatment of MDR HIV-1 461:486 The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. 35262531 5 31 theme % 1017:1017 arg1 MPI 1008:1010 a median MPI 999:1010 a median MPI of 93% 999:1017 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 5 31 theme % 1017:1017 arg1 replication 893:903 viral replication 887:903 viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), 887:993 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 8 32 theme those 1390:1394 arg1 range 1381:1385 the range 1377:1385 the range of those reported for HIV-1 1377:1413 CONCLUSION Ibalizumab inhibits HIV-2 replication, with IC 50 and MPI in the range of those reported for HIV-1. 35262531 4 33 theme maximum 744:750 arg1 MPI 776:778 MPI 776:778 MPI 776:778 Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility. 35262531 4 33 theme maximum 744:750 arg1 inhibitions 763:773 maximum percentage inhibitions 744:773 maximum percentage inhibitions (MPI) 744:779 Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility. 35262531 2 34 theme isolates 364:371 arg1 susceptibility 332:345 the susceptibility 328:345 the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1 328:486 The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. 35262531 5 35 theme IC 939:940 arg1 value 945:949 a median IC 50 value 930:949 a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml) 930:992 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 2 36 theme HIV-2 350:354 arg1 isolates 364:371 HIV-2 primary isolates 350:371 HIV-2 primary isolates 350:371 The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. 35262531 2 37 theme monoclonal 402:411 arg1 antibody 413:420 a long-acting monoclonal antibody 388:420 a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1 388:486 The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. 35262531 2 37 theme monoclonal 402:411 arg1 ibalizumab 376:385 ibalizumab 376:385 ibalizumab 376:385 The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. 35262531 4 38 theme % 712:712 arg1 concentrations 725:738 50% inhibitory concentrations 710:738 50% inhibitory concentrations 710:738 Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility. 35262531 0 39 theme in-vitro 17:24 arg1 activity 26:33 in-vitro activity 17:33 in-vitro activity against group A and group B HIV-2 clinical isolates 17:85 Ibalizumab shows in-vitro activity against group A and group B HIV-2 clinical isolates. 35262531 1 40 theme active 272:277 arg1 antiretrovirals 256:270 antiretrovirals 256:270 antiretrovirals active on HIV-2 256:286 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 3 41 theme peripheral 611:620 arg1 PBMC 647:650 PBMC 647:650 PBMC 647:650 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 3 41 theme peripheral 611:620 arg1 cells 640:644 peripheral blood mononuclear cells 611:644 a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay 580:657 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 9 42 theme ibalizumab 1455:1464 arg1 use 1448:1450 the use 1444:1450 the use of ibalizumab in patients with MDR HIV-2 1444:1491 These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen. 35262531 0 43 theme group 55:59 arg1 B 61:61 group B 55:61 group B 55:61 Ibalizumab shows in-vitro activity against group A and group B HIV-2 clinical isolates. 35262531 0 44 theme A 49:49 arg1 isolates 78:85 group A and group B HIV-2 clinical isolates 43:85 group A and group B HIV-2 clinical isolates 43:85 Ibalizumab shows in-vitro activity against group A and group B HIV-2 clinical isolates. 35262531 6 45 theme higher 1052:1057 arg1 0.1 μg/ml 1072:1080 above 0.1 μg/ml 1066:1080 above 0.1 μg/ml 1066:1080 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 6 45 theme higher 1052:1057 arg1 IC 1059:1060 higher IC 50 1052:1063 higher IC 50 (above 0.1 μg/ml) 1052:1081 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 8 46 theme CONCLUSION 1305:1314 arg1 Ibalizumab 1316:1325 CONCLUSION Ibalizumab 1305:1325 CONCLUSION Ibalizumab 1305:1325 CONCLUSION Ibalizumab inhibits HIV-2 replication, with IC 50 and MPI in the range of those reported for HIV-1. 35262531 5 47 theme range 967:971 arg1 0.027 μg/ml 954:964 0.027 μg/ml 954:964 0.027 μg/ml (range = 0.001-0.506 μg/ml) 954:992 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 5 47 theme range 967:971 arg1 0.001-0.506 μg/ml 975:991 range = 0.001-0.506 μg/ml 967:991 range = 0.001-0.506 μg/ml 967:991 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 9 48 theme MDR 1483:1485 arg1 HIV-2 1487:1491 MDR HIV-2 1483:1491 MDR HIV-2 1483:1491 These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen. 35262531 3 49 theme mononuclear 628:638 arg1 PBMC 647:650 PBMC 647:650 PBMC 647:650 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 3 49 theme mononuclear 628:638 arg1 cells 640:644 peripheral blood mononuclear cells 611:644 a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay 580:657 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 1 50 theme virological 214:224 arg1 failure 226:232 virological failure 214:232 virological failure 214:232 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 5 51 theme 0.027 μg/ml 954:964 arg1 value 945:949 a median IC 50 value 930:949 a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml) 930:992 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 6 52 from loop 1160:1163 arg1 loss 1107:1110 a loss 1105:1110 a loss of potential N-linked glycosylation sites in V5 loop 1105:1163 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 9 53 theme background 1527:1536 arg1 regimen 1538:1544 an optimized background regimen 1514:1544 an optimized background regimen 1514:1544 These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen. 35262531 5 54 with isolates 915:922 arg1 value 945:949 a median IC 50 value 930:949 a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml) 930:992 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 6 55 theme above 1066:1070 arg1 0.1 μg/ml 1072:1080 above 0.1 μg/ml 1066:1080 above 0.1 μg/ml 1066:1080 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 6 55 theme above 1066:1070 arg1 IC 1059:1060 higher IC 50 1052:1063 higher IC 50 (above 0.1 μg/ml) 1052:1081 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 7 56 theme HIV-2 1281:1285 arg1 strain 1297:1302 the HIV-2 reference strain 1277:1302 the HIV-2 reference strain 1277:1302 However, both presented shorter V1 and V2 loops than the HIV-2 reference strain. 35262531 6 57 link N-linked 1125:1132 arg1 sites 1148:1152 potential N-linked glycosylation sites 1115:1152 potential N-linked glycosylation sites in V5 loop 1115:1163 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 1 58 theme mutations 193:201 arg1 selection 180:188 the rapid selection 170:188 the rapid selection of mutations at time of virological failure 170:232 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 1 58 theme mutations 193:201 arg1 number 246:251 the low number 238:251 the low number of antiretrovirals active on HIV-2 238:286 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 6 59 theme N-linked 1125:1132 arg1 sites 1148:1152 potential N-linked glycosylation sites 1115:1152 potential N-linked glycosylation sites in V5 loop 1115:1163 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 6 60 theme reduced 1200:1206 arg1 susceptibility 1208:1221 reduced susceptibility 1200:1221 reduced susceptibility 1200:1221 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 3 61 theme primary 544:550 arg1 isolates 552:559 16 HIV-2 primary isolates 535:559 16 HIV-2 primary isolates 535:559 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 4 62 theme susceptibility 842:855 arg1 determinants 818:829 determinants 818:829 determinants of reduced susceptibility 818:855 Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility. 35262531 7 63 theme V2 1263:1264 arg1 loops 1266:1270 shorter V1 and V2 loops 1248:1270 shorter V1 and V2 loops 1248:1270 However, both presented shorter V1 and V2 loops than the HIV-2 reference strain. 35262531 1 64 from time 206:209 arg1 mutations 193:201 mutations 193:201 mutations at time of virological failure 193:232 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 1 64 from time 206:209 arg1 selection 180:188 the rapid selection 170:188 the rapid selection of mutations at time of virological failure 170:232 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 1 64 from time 206:209 arg1 number 246:251 the low number 238:251 the low number of antiretrovirals active on HIV-2 238:286 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 3 65 theme modified 582:589 arg1 version 591:597 a modified version 580:597 a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay 580:657 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 1 66 theme HIV-2 131:135 arg1 issue 152:156 an emerging issue 140:156 an emerging issue 140:156 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 1 66 theme HIV-2 131:135 arg1 Treatment 98:106 OBJECTIVE Treatment 88:106 OBJECTIVE Treatment of multidrug-resistant HIV-2 88:135 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 9 67 from use 1448:1450 arg1 patients 1469:1476 patients 1469:1476 patients with MDR HIV-2 1469:1491 These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen. 35262531 7 68 theme V1 1256:1257 arg1 loops 1266:1270 shorter V1 and V2 loops 1248:1270 shorter V1 and V2 loops 1248:1270 However, both presented shorter V1 and V2 loops than the HIV-2 reference strain. 35262531 0 69 theme B 61:61 arg1 isolates 78:85 group A and group B HIV-2 clinical isolates 43:85 group A and group B HIV-2 clinical isolates 43:85 Ibalizumab shows in-vitro activity against group A and group B HIV-2 clinical isolates. 35262531 3 70 dep susceptibility 517:530 arg1 In-vitro 497:504 In-vitro 497:504 In-vitro 497:504 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 0 71 theme clinical 69:76 arg1 isolates 78:85 group A and group B HIV-2 clinical isolates 43:85 group A and group B HIV-2 clinical isolates 43:85 Ibalizumab shows in-vitro activity against group A and group B HIV-2 clinical isolates. 35262531 5 72 theme RESULTS 858:864 arg1 Ibalizumab 866:875 RESULTS Ibalizumab 858:875 RESULTS Ibalizumab 858:875 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 6 73 from loss 1107:1110 arg1 loop 1160:1163 V5 loop 1157:1163 V5 loop 1157:1163 Although two isolates presented higher IC 50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. 35262531 2 74 theme MDR 478:480 arg1 HIV-1 482:486 MDR HIV-1 478:486 MDR HIV-1 478:486 The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. 35262531 4 75 theme inhibitory 714:723 arg1 concentrations 725:738 50% inhibitory concentrations 710:738 50% inhibitory concentrations 710:738 Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility. 35262531 5 76 theme median 932:937 arg1 value 945:949 a median IC 50 value 930:949 a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml) 930:992 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 2 77 theme primary 356:362 arg1 isolates 364:371 HIV-2 primary isolates 350:371 HIV-2 primary isolates 350:371 The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. 35262531 1 78 theme antiretrovirals 256:270 arg1 selection 180:188 the rapid selection 170:188 the rapid selection of mutations at time of virological failure 170:232 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 1 78 theme antiretrovirals 256:270 arg1 number 246:251 the low number 238:251 the low number of antiretrovirals active on HIV-2 238:286 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 35262531 5 79 theme isolates 915:922 arg1 MPI 1008:1010 a median MPI 999:1010 a median MPI of 93% 999:1017 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 5 79 theme isolates 915:922 arg1 replication 893:903 viral replication 887:903 viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), 887:993 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 2 80 theme long-acting 390:400 arg1 antibody 413:420 a long-acting monoclonal antibody 388:420 a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1 388:486 The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. 35262531 2 80 theme long-acting 390:400 arg1 ibalizumab 376:385 ibalizumab 376:385 ibalizumab 376:385 The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. 35262531 9 81 theme in 1422:1423 arg1 data 1431:1434 These in vitro data 1416:1434 These in vitro data 1416:1434 These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen. 35262531 3 82 theme ANRS 606:609 arg1 version 591:597 a modified version 580:597 a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay 580:657 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 4 83 theme 50 710:711 arg1 % 712:712 % 712:712 % 712:712 Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility. 35262531 0 84 theme group 43:47 arg1 A 49:49 group A 43:49 group A 43:49 Ibalizumab shows in-vitro activity against group A and group B HIV-2 clinical isolates. 35262531 5 85 theme = 973:973 arg1 0.027 μg/ml 954:964 0.027 μg/ml 954:964 0.027 μg/ml (range = 0.001-0.506 μg/ml) 954:992 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 5 85 theme = 973:973 arg1 0.001-0.506 μg/ml 975:991 range = 0.001-0.506 μg/ml 967:991 range = 0.001-0.506 μg/ml 967:991 RESULTS Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027 μg/ml (range = 0.001-0.506 μg/ml), and a median MPI of 93%. 35262531 3 86 theme cells 640:644 arg1 assay 653:657 a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay 580:657 a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay 580:657 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 2 87 theme study 305:309 arg1 aim 293:295 The aim 289:295 The aim of this study 289:309 The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. 35262531 3 88 theme blood 622:626 arg1 PBMC 647:650 PBMC 647:650 PBMC 647:650 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 3 88 theme blood 622:626 arg1 cells 640:644 peripheral blood mononuclear cells 611:644 a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay 580:657 METHODS In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. 35262531 4 89 theme percentage 752:761 arg1 MPI 776:778 MPI 776:778 MPI 776:778 Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility. 35262531 4 89 theme percentage 752:761 arg1 inhibitions 763:773 maximum percentage inhibitions 744:773 maximum percentage inhibitions (MPI) 744:779 Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility. 35262531 1 90 theme failure 226:232 arg1 time 206:209 time 206:209 time of virological failure 206:232 OBJECTIVE Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. 37054624 1 0 theme glycopeptides 281:293 arg1 enrichment 258:267 the highly efficient enrichment 237:267 the highly efficient enrichment of N-linked glycopeptides 237:293 The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. 37054624 3 1 theme IgG 699:701 arg1 ratio 678:682 molar ratio 672:682 molar ratio of human serum IgG to BSA digests 672:716 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 1 2 link N-linked 272:279 arg1 glycopeptides 281:293 N-linked glycopeptides 272:293 N-linked glycopeptides 272:293 The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. 37054624 3 3 theme @ 543:543 arg1 @ 547:547 The resultant COFTP-TAPT@PEI@ 519:547 The resultant COFTP-TAPT@PEI@Carr 519:551 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 3 theme @ 543:543 arg1 Carr 548:551 Carr 548:551 Carr 548:551 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 4 dep 1:800 665:669 arg1 ratio 678:682 molar ratio 672:682 molar ratio of human serum IgG to BSA digests 672:716 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 5 theme human 687:691 arg1 IgG 699:701 human serum IgG 687:701 human serum IgG 687:701 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 5 6 with groups 1361:1366 arg1 carcinoma 1401:1409 nasopharyngeal carcinoma 1386:1409 nasopharyngeal carcinoma 1386:1409 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 5 7 theme patients 1372:1379 arg1 digests 1338:1344 2 μL plasma trypsin digests 1318:1344 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma 1318:1409 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 3 8 theme resultant 523:531 arg1 @ 547:547 The resultant COFTP-TAPT@PEI@ 519:547 The resultant COFTP-TAPT@PEI@Carr 519:551 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 8 theme resultant 523:531 arg1 Carr 548:551 Carr 548:551 Carr 548:551 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 4 9 theme subjects 1073:1080 arg1 plasma 1055:1060 the human plasma 1045:1060 the human plasma of healthy subjects and patients with nasopharyngeal carcinoma 1045:1123 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 5 10 theme nasopharyngeal 1386:1399 arg1 carcinoma 1401:1409 nasopharyngeal carcinoma 1386:1409 nasopharyngeal carcinoma 1386:1409 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 2 11 theme timesaving 323:332 arg1 route 334:338 a facile and timesaving route 310:338 a facile and timesaving route 310:338 In this work, a facile and timesaving route was introduced in which COFTP-TAPT served as a carrier and poly (ethylenimine) (PEI) and carrageenan (Carr) were successively coated on the surface via electrostatic interaction. 37054624 4 12 theme brilliant 845:853 arg1 hydrophilicity 855:868 brilliant hydrophilicity 845:868 brilliant hydrophilicity 845:868 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 3 13 gly glycopeptide 586:597 arg2 glycopeptide 586:597 glycopeptide enrichment 586:608 glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times) 586:831 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 14 theme BSA 706:708 arg1 digests 710:716 BSA digests 706:716 BSA digests 706:716 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 6 15 gly glycopeptides 1496:1508 arg2 glycopeptides 1496:1508 53 glycopeptides 1493:1508 53 glycopeptides 1493:1508 22 glycopeptides were identified only from the normal controls and 53 glycopeptides were detected only from the other set. 37054624 2 16 theme facile 312:317 arg1 route 334:338 a facile and timesaving route 310:338 a facile and timesaving route 310:338 In this work, a facile and timesaving route was introduced in which COFTP-TAPT served as a carrier and poly (ethylenimine) (PEI) and carrageenan (Carr) were successively coated on the surface via electrostatic interaction. 37054624 4 17 theme human 1049:1053 arg1 plasma 1055:1060 the human plasma 1045:1060 the human plasma of healthy subjects and patients with nasopharyngeal carcinoma 1045:1123 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 3 18 dep selectivity 652:662 arg1 1:800 665:669 1:800 665:669 1:800 665:669 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 19 theme glycopeptide 586:597 arg1 enrichment 599:608 glycopeptide enrichment 586:608 glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times) 586:831 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 20 theme large 720:724 arg1 300 mg g-1 744:753 300 mg g-1 744:753 300 mg g-1 744:753 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 20 theme large 720:724 arg1 capacity 734:741 large loading capacity 720:741 large loading capacity (300 mg g-1) 720:754 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 1 21 theme synthetic 152:160 arg1 materials 162:170 facilely synthetic materials 143:170 facilely synthetic materials 143:170 The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. 37054624 4 22 theme patients 1086:1093 arg1 plasma 1055:1060 the human plasma 1045:1060 the human plasma of healthy subjects and patients with nasopharyngeal carcinoma 1045:1123 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 1 23 from role 190:193 arg1 analysis 212:219 glycoproteome analysis 198:219 glycoproteome analysis 198:219 The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. 37054624 4 24 theme nasopharyngeal 1100:1113 arg1 carcinoma 1115:1123 nasopharyngeal carcinoma 1100:1123 nasopharyngeal carcinoma 1100:1123 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 0 25 theme selective 83:91 arg1 enrichment 93:102 highly selective enrichment 76:102 highly selective enrichment of N-glycopeptides 76:121 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 37054624 6 26 gly glycopeptides 1429:1441 arg2 glycopeptides 1429:1441 22 glycopeptides 1426:1441 22 glycopeptides 1426:1441 22 glycopeptides were identified only from the normal controls and 53 glycopeptides were detected only from the other set. 37054624 1 27 theme essential 180:188 arg1 role 190:193 an essential role 177:193 an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides 177:293 The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. 37054624 5 28 gly glycosylation 1168:1180 arg2 sites 1182:1186 141 glycosylation sites 1164:1186 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins 1164:1297 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 5 28 gly glycosylation 1168:1180 arg2 141 1164:1166 141 1164:1166 141 1164:1166 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 4 29 dep hydrophilicity 855:868 arg1 the 841:843 the 841:843 the 841:843 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 2 30 theme electrostatic 492:504 arg1 interaction 506:516 electrostatic interaction 492:516 electrostatic interaction 492:516 In this work, a facile and timesaving route was introduced in which COFTP-TAPT served as a carrier and poly (ethylenimine) (PEI) and carrageenan (Carr) were successively coated on the surface via electrostatic interaction. 37054624 1 31 gly glycopeptides 281:293 arg2 glycopeptides 281:293 N-linked glycopeptides 272:293 N-linked glycopeptides 272:293 The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. 37054624 2 32 dep introduced 344:353 arg1 served 375:380 served 375:380 served as a carrier and poly (ethylenimine) (PEI) 375:423 In this work, a facile and timesaving route was introduced in which COFTP-TAPT served as a carrier and poly (ethylenimine) (PEI) and carrageenan (Carr) were successively coated on the surface via electrostatic interaction. 37054624 2 32 dep introduced 344:353 arg1 coated 466:471 coated 466:471 were successively coated on the surface via electrostatic interaction 448:516 In this work, a facile and timesaving route was introduced in which COFTP-TAPT served as a carrier and poly (ethylenimine) (PEI) and carrageenan (Carr) were successively coated on the surface via electrostatic interaction. 37054624 5 33 theme 2 μL 1318:1321 arg1 digests 1338:1344 2 μL plasma trypsin digests 1318:1344 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma 1318:1409 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 0 34 theme Facile 0:5 arg1 fabrication 7:17 Facile fabrication 0:17 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 0:122 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 37054624 4 35 dep identification 1014:1027 arg1 the 1010:1012 the 1010:1012 the 1010:1012 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 0 36 gly N-glycopeptides 107:121 arg2 N-glycopeptides 107:121 N-glycopeptides 107:121 N-glycopeptides 107:121 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 37054624 7 37 theme N-glycoproteome 1648:1662 arg1 research 1664:1671 further N-glycoproteome research 1640:1671 further N-glycoproteome research 1640:1671 The results demonstrated that this hydrophilic material was promising on a large scale and further N-glycoproteome research. 37054624 3 38 from performance 571:581 arg1 enrichment 599:608 glycopeptide enrichment 586:608 glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times) 586:831 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 5 39 with patients 1372:1379 arg1 carcinoma 1401:1409 nasopharyngeal carcinoma 1386:1409 nasopharyngeal carcinoma 1386:1409 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 4 40 with subjects 1073:1080 arg1 carcinoma 1115:1123 nasopharyngeal carcinoma 1100:1123 nasopharyngeal carcinoma 1100:1123 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 0 41 theme covalent 34:41 arg1 composites 61:70 hydrophilic covalent organic framework composites 22:70 hydrophilic covalent organic framework composites 22:70 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 37054624 5 42 gly glycosylation 1250:1262 arg2 sites 1264:1268 177 glycosylation sites 1246:1268 177 glycosylation sites corresponding to 67 proteins 1246:1297 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 5 42 gly glycosylation 1250:1262 arg2 177 1246:1248 177 1246:1248 177 1246:1248 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 5 43 theme control 1353:1359 arg1 groups 1361:1366 the control groups 1349:1366 the control groups 1349:1366 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 0 44 theme framework 51:59 arg1 composites 61:70 hydrophilic covalent organic framework composites 22:70 hydrophilic covalent organic framework composites 22:70 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 37054624 5 45 with 113 N-glycopeptides 1139:1157 arg1 sites 1182:1186 141 glycosylation sites 1164:1186 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins 1164:1297 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 6 46 theme normal 1473:1478 arg1 controls 1480:1487 the normal controls 1469:1487 the normal controls 1469:1487 22 glycopeptides were identified only from the normal controls and 53 glycopeptides were detected only from the other set. 37054624 5 47 theme glycosylation 1168:1180 arg1 sites 1182:1186 141 glycosylation sites 1164:1186 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins 1164:1297 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 5 48 theme trypsin 1330:1336 arg1 digests 1338:1344 2 μL plasma trypsin digests 1318:1344 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma 1318:1409 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 4 49 gly glycopeptides 952:964 arg2 glycopeptides 952:964 positively charged glycopeptides 933:964 positively charged glycopeptides 933:964 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 1 50 theme N-linked 272:279 arg1 glycopeptides 281:293 N-linked glycopeptides 272:293 N-linked glycopeptides 272:293 The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. 37054624 3 51 theme molar 672:676 arg1 ratio 678:682 molar ratio 672:682 molar ratio of human serum IgG to BSA digests 672:716 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 52 theme COFTP-TAPT 533:542 arg1 @ 547:547 The resultant COFTP-TAPT@PEI@ 519:547 The resultant COFTP-TAPT@PEI@Carr 519:551 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 52 theme COFTP-TAPT 533:542 arg1 Carr 548:551 Carr 548:551 Carr 548:551 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 4 53 theme healthy 1065:1071 arg1 subjects 1073:1080 healthy subjects 1065:1080 healthy subjects 1065:1080 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 4 54 with patients 1086:1093 arg1 carcinoma 1115:1123 nasopharyngeal carcinoma 1100:1123 nasopharyngeal carcinoma 1100:1123 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 3 55 theme serum 693:697 arg1 IgG 699:701 human serum IgG 687:701 human serum IgG 687:701 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 1 56 theme glycoproteome 198:210 arg1 analysis 212:219 glycoproteome analysis 198:219 glycoproteome analysis 198:219 The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. 37054624 7 57 theme large 1624:1628 arg1 scale 1630:1634 a large scale 1622:1634 a large scale 1622:1634 The results demonstrated that this hydrophilic material was promising on a large scale and further N-glycoproteome research. 37054624 3 58 theme PEI 544:546 arg1 @ 547:547 The resultant COFTP-TAPT@PEI@ 519:547 The resultant COFTP-TAPT@PEI@Carr 519:551 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 58 theme PEI 544:546 arg1 Carr 548:551 Carr 548:551 Carr 548:551 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 59 theme remarkable 560:569 arg1 performance 571:581 remarkable performance 560:581 remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times) 560:831 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 4 60 from analysis 1033:1040 arg1 plasma 1055:1060 the human plasma 1045:1060 the human plasma of healthy subjects and patients with nasopharyngeal carcinoma 1045:1123 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 7 61 theme hydrophilic 1584:1594 arg1 material 1596:1603 this hydrophilic material 1579:1603 this hydrophilic material 1579:1603 The results demonstrated that this hydrophilic material was promising on a large scale and further N-glycoproteome research. 37054624 3 62 theme loading 726:732 arg1 300 mg g-1 744:753 300 mg g-1 744:753 300 mg g-1 744:753 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 62 theme loading 726:732 arg1 capacity 734:741 large loading capacity 720:741 large loading capacity (300 mg g-1) 720:754 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 63 theme high 615:618 arg1 2 fmol μL-1 633:643 2 fmol μL-1 633:643 2 fmol μL-1 633:643 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 63 theme high 615:618 arg1 sensitivity 620:630 high sensitivity 615:630 high sensitivity (2 fmol μL-1) 615:644 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 4 64 from identification 1014:1027 arg1 plasma 1055:1060 the human plasma 1045:1060 the human plasma of healthy subjects and patients with nasopharyngeal carcinoma 1045:1123 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 5 65 theme glycosylation 1250:1262 arg1 sites 1264:1268 177 glycosylation sites 1246:1268 177 glycosylation sites corresponding to 67 proteins 1246:1297 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 3 66 theme satisfactory 757:768 arg1 recovery 770:777 satisfactory recovery 757:777 satisfactory recovery (102.4 ± 6.0%) 757:792 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 66 theme satisfactory 757:768 arg1 % 791:791 102.4 ± 6.0% 780:791 102.4 ± 6.0% 780:791 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 67 with enrichment 599:608 arg1 2 fmol μL-1 633:643 2 fmol μL-1 633:643 2 fmol μL-1 633:643 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 67 with enrichment 599:608 arg1 reusability 798:808 reusability 798:808 reusability (at least eight times) 798:831 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 67 with enrichment 599:608 arg1 % 791:791 102.4 ± 6.0% 780:791 102.4 ± 6.0% 780:791 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 67 with enrichment 599:608 arg1 capacity 734:741 large loading capacity 720:741 large loading capacity (300 mg g-1) 720:754 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 67 with enrichment 599:608 arg1 recovery 770:777 satisfactory recovery 757:777 satisfactory recovery (102.4 ± 6.0%) 757:792 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 67 with enrichment 599:608 arg1 sensitivity 620:630 high sensitivity 615:630 high sensitivity (2 fmol μL-1) 615:644 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 67 with enrichment 599:608 arg1 selectivity 652:662 high selectivity 647:662 high selectivity (1:800, molar ratio of human serum IgG to BSA digests) 647:717 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 67 with enrichment 599:608 arg1 300 mg g-1 744:753 300 mg g-1 744:753 300 mg g-1 744:753 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 3 67 with enrichment 599:608 arg1 times 826:830 at least eight times 811:830 at least eight times 811:830 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 1 68 theme materials 162:170 arg1 development 128:138 The development 124:138 The development of facilely synthetic materials 124:170 The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. 37054624 5 69 with 144 N-glycopeptides 1221:1239 arg1 sites 1264:1268 177 glycosylation sites 1246:1268 177 glycosylation sites corresponding to 67 proteins 1246:1297 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 6 70 theme other 1538:1542 arg1 set 1544:1546 the other set 1534:1546 the other set 1534:1546 22 glycopeptides were identified only from the normal controls and 53 glycopeptides were detected only from the other set. 37054624 3 71 theme high 647:650 arg1 selectivity 652:662 high selectivity 647:662 high selectivity (1:800, molar ratio of human serum IgG to BSA digests) 647:717 The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol μL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). 37054624 0 72 theme N-glycopeptides 107:121 arg1 enrichment 93:102 highly selective enrichment 76:102 highly selective enrichment of N-glycopeptides 76:121 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 37054624 5 73 with proteins 1208:1215 arg1 sites 1264:1268 177 glycosylation sites 1246:1268 177 glycosylation sites corresponding to 67 proteins 1246:1297 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 4 74 theme electrostatic 874:886 arg1 interactions 888:899 electrostatic interactions 874:899 electrostatic interactions 874:899 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 5 75 gly 113 N-glycopeptides 1139:1157 arg2 result 1131:1136 a result 1129:1136 a result 1129:1136 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 5 75 gly 113 N-glycopeptides 1139:1157 arg2 113 N-glycopeptides 1139:1157 113 N-glycopeptides 1139:1157 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins 1139:1297 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 0 76 theme hydrophilic 22:32 arg1 composites 61:70 hydrophilic covalent organic framework composites 22:70 hydrophilic covalent organic framework composites 22:70 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 37054624 4 77 theme prepared 971:978 arg1 materials 980:988 the prepared materials 967:988 the prepared materials 967:988 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 0 78 theme organic 43:49 arg1 composites 61:70 hydrophilic covalent organic framework composites 22:70 hydrophilic covalent organic framework composites 22:70 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 37054624 7 79 theme further 1640:1646 arg1 research 1664:1671 further N-glycoproteome research 1640:1671 further N-glycoproteome research 1640:1671 The results demonstrated that this hydrophilic material was promising on a large scale and further N-glycoproteome research. 37054624 0 80 theme composites 61:70 arg1 fabrication 7:17 Facile fabrication 0:17 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 0:122 Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides. 37054624 4 81 theme charged 944:950 arg1 glycopeptides 952:964 positively charged glycopeptides 933:964 positively charged glycopeptides 933:964 Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. 37054624 5 82 theme groups 1361:1366 arg1 digests 1338:1344 2 μL plasma trypsin digests 1318:1344 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma 1318:1409 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 5 83 gly 144 N-glycopeptides 1221:1239 arg2 144 N-glycopeptides 1221:1239 144 N-glycopeptides 1221:1239 144 N-glycopeptides 1221:1239 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 5 84 theme plasma 1323:1328 arg1 digests 1338:1344 2 μL plasma trypsin digests 1318:1344 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma 1318:1409 As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 μL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 37054624 1 85 theme efficient 248:256 arg1 enrichment 258:267 the highly efficient enrichment 237:267 the highly efficient enrichment of N-linked glycopeptides 237:293 The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. 36747715 3 0 theme metabolic 473:481 arg1 effects 483:489 metabolic effects 473:489 metabolic effects 473:489 We applied CRISPR screens to test IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable crossover. 36747715 6 1 theme transcription 844:856 arg1 Bcl11b 865:870 the transcription factor Bcl11b 840:870 the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress 840:973 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 5 2 theme T 740:740 arg1 cells 747:751 T H 17 cells 740:751 T H 17 cells 740:751 Interestingly, Gfpt1 -deficient T H 1 cells were more affected than T H 17 cells, which had increased Nagk for salvage UDP-GlcNAc synthesis. 36747715 7 3 theme IEI 1045:1047 arg1 genes 1049:1053 IEM and IEI genes 1037:1053 IEM and IEI genes 1037:1053 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 3 4 theme considerable 501:512 arg1 crossover 514:522 considerable crossover 501:522 considerable crossover 501:522 We applied CRISPR screens to test IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable crossover. 36747715 6 5 theme IEI 823:825 arg1 genes 827:831 Screening IEI genes 813:831 Screening IEI genes 813:831 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 4 6 theme T 641:641 arg1 cell 643:646 T cell expansion and function 641:669 cell 643:646 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 7 7 theme IEM 1037:1039 arg1 genes 1049:1053 IEM and IEI genes 1037:1053 IEM and IEI genes 1037:1053 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 1 8 theme Mendelian 173:181 arg1 diseases 183:190 Mendelian diseases 173:190 Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations 173:268 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 1 8 theme Mendelian 173:181 arg1 Errors 123:128 Inborn Errors 116:128 Inborn Errors of Metabolism (IEM) and Immunity (IEI) 116:167 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 8 9 theme Inborn 1171:1176 arg1 errors 1178:1183 Inborn errors 1171:1183 Inborn errors of immunity and metabolism 1171:1210 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 6 10 theme mitochondrial 894:906 arg1 activity 908:915 CD4 + T cell mitochondrial activity 881:915 CD4 + T cell mitochondrial activity 881:915 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 5 11 theme salvage 783:789 arg1 synthesis 802:810 salvage UDP-GlcNAc synthesis 783:810 salvage UDP-GlcNAc synthesis 783:810 Interestingly, Gfpt1 -deficient T H 1 cells were more affected than T H 17 cells, which had increased Nagk for salvage UDP-GlcNAc synthesis. 36747715 6 12 theme T 887:887 arg1 cell 889:892 T cell 887:892 T cell 887:892 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 8 13 theme mitochondrial 1397:1409 arg1 function 1411:1418 mitochondrial function 1397:1418 mitochondrial function 1397:1418 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 8 14 theme Gfpt1 1255:1259 arg1 deficiency 1261:1270 previously known Gfpt1 deficiency 1238:1270 previously known Gfpt1 deficiency 1238:1270 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 7 15 theme high 1000:1003 arg1 degree 1005:1010 a high degree 998:1010 a high degree of functional overlap of IEM and IEI genes 998:1053 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 6 16 theme CD4 881:883 arg1 activity 908:915 CD4 + T cell mitochondrial activity 881:915 CD4 + T cell mitochondrial activity 881:915 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 8 17 theme Many 1420:1423 arg1 IEM 1425:1427 Many IEM 1420:1427 Many IEM 1420:1427 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 1 18 theme Metabolism 133:142 arg1 diseases 183:190 Mendelian diseases 173:190 Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations 173:268 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 1 18 theme Metabolism 133:142 arg1 Errors 123:128 Inborn Errors 116:128 Inborn Errors of Metabolism (IEM) and Immunity (IEI) 116:167 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 0 19 theme Metabolism 52:61 arg1 Genes 63:67 Metabolism Genes 52:67 Metabolism Genes 52:67 Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities. 36747715 6 20 theme metabolic 958:966 arg1 stress 968:973 metabolic stress 958:973 metabolic stress 958:973 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 8 21 theme immune 1438:1443 arg1 defects 1445:1451 immune defects 1438:1451 immune defects 1438:1451 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 8 22 dep Bcl11b 1344:1349 arg1 causes 1351:1356 causes 1351:1356 causes a T cell deficiency IEI 1351:1380 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 0 23 theme Cell 78:81 arg1 Vulnerabilities 99:113 T Cell Immunometabolic Vulnerabilities 76:113 T Cell Immunometabolic Vulnerabilities 76:113 Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities. 36747715 8 24 theme cell 1319:1322 arg1 Loss 1336:1339 T cell subset fate Loss 1317:1339 T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI 1317:1380 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 8 25 dep greater 1217:1223 arg1 overlap 1225:1231 overlap 1225:1231 overlap 1225:1231 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 8 26 theme fate 1331:1334 arg1 Loss 1336:1339 T cell subset fate Loss 1317:1339 T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI 1317:1380 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 3 27 theme CRISPR 400:405 arg1 screens 407:413 CRISPR screens 400:413 CRISPR screens 400:413 We applied CRISPR screens to test IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable crossover. 36747715 1 28 theme clinical 249:256 arg1 annotations 258:268 clinical annotations 249:268 clinical annotations 249:268 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 5 29 theme -deficient 693:702 arg1 cells 710:714 Gfpt1 -deficient T H 1 cells 687:714 Gfpt1 -deficient T H 1 cells 687:714 Interestingly, Gfpt1 -deficient T H 1 cells were more affected than T H 17 cells, which had increased Nagk for salvage UDP-GlcNAc synthesis. 36747715 8 30 theme metabolic 1478:1486 arg1 mechanisms 1488:1497 metabolic mechanisms 1478:1497 metabolic mechanisms 1478:1497 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 6 31 theme Screening 813:821 arg1 genes 827:831 Screening IEI genes 813:831 Screening IEI genes 813:831 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 4 32 theme IEM 537:539 arg1 Analysis 525:532 Analysis 525:532 Analysis of IEM 525:539 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 3 33 theme IEM 423:425 arg1 genes 427:431 IEM genes 423:431 IEM genes for immunologic roles 423:453 We applied CRISPR screens to test IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable crossover. 36747715 1 34 theme Immunity 154:161 arg1 diseases 183:190 Mendelian diseases 173:190 Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations 173:268 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 1 34 theme Immunity 154:161 arg1 Errors 123:128 Inborn Errors 116:128 Inborn Errors of Metabolism (IEM) and Immunity (IEI) 116:167 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 0 35 theme Errors 29:34 arg1 Functional 0:9 Functional 0:9 Functional 0:9 Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities. 36747715 8 36 theme T 1360:1360 arg1 IEI 1378:1380 a T cell deficiency IEI 1358:1380 a T cell deficiency IEI 1358:1380 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 3 37 theme IEI 459:461 arg1 genes 463:467 IEI genes 459:467 IEI genes 459:467 We applied CRISPR screens to test IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable crossover. 36747715 0 38 theme Immunity 39:46 arg1 Errors 29:34 Inborn Errors 22:34 Inborn Errors of Immunity and Metabolism Genes 22:67 Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities. 36747715 8 39 dep harms 1391:1395 arg1 have 1433:1436 have 1433:1436 may have immune defects 1429:1451 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 8 40 theme deficiency 1367:1376 arg1 IEI 1378:1380 a T cell deficiency IEI 1358:1380 a T cell deficiency IEI 1358:1380 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 4 41 theme de 579:580 arg1 Gfpt1 616:620 Gfpt1 616:620 Gfpt1 616:620 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 4 41 theme de 579:580 arg1 critical 628:635 critical 628:635 critical 628:635 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 4 41 theme de 579:580 arg1 enzyme 608:613 the de novo hexosamine synthesis enzyme 575:613 the de novo hexosamine synthesis enzyme 575:613 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 5 42 theme H 742:742 arg1 cells 747:751 T H 17 cells 740:751 T H 17 cells 740:751 Interestingly, Gfpt1 -deficient T H 1 cells were more affected than T H 17 cells, which had increased Nagk for salvage UDP-GlcNAc synthesis. 36747715 0 43 dep Functional 0:9 arg1 Overlap 11:17 Overlap 11:17 Overlap 11:17 Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities. 36747715 4 44 theme hexosamine 587:596 arg1 Gfpt1 616:620 Gfpt1 616:620 Gfpt1 616:620 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 4 44 theme hexosamine 587:596 arg1 critical 628:635 critical 628:635 critical 628:635 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 4 44 theme hexosamine 587:596 arg1 enzyme 608:613 the de novo hexosamine synthesis enzyme 575:613 the de novo hexosamine synthesis enzyme 575:613 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 7 45 dep functional 1015:1024 arg1 overlap 1026:1032 overlap 1026:1032 overlap 1026:1032 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 1 46 theme patient 224:230 arg1 rarity 232:237 patient rarity 224:237 patient rarity 224:237 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 6 47 theme factor 858:863 arg1 Bcl11b 865:870 the transcription factor Bcl11b 840:870 the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress 840:973 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 4 48 theme N-linked 548:555 arg1 glycosylation 557:569 N-linked glycosylation 548:569 N-linked glycosylation 548:569 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 7 49 theme genes 1049:1053 arg1 functional 1015:1024 functional 1015:1024 functional 1015:1024 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 2 50 theme Few 271:273 arg1 genes 275:279 Few genes 271:279 Few genes 271:279 Few genes are assigned to both IEM and IEI, but immunometabolic demands suggest functional overlap is underestimated. 36747715 6 51 dep Bcl11b 865:870 arg1 promotes 872:879 promotes 872:879 promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress 872:973 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 5 52 theme UDP-GlcNAc 791:800 arg1 synthesis 802:810 salvage UDP-GlcNAc synthesis 783:810 salvage UDP-GlcNAc synthesis 783:810 Interestingly, Gfpt1 -deficient T H 1 cells were more affected than T H 17 cells, which had increased Nagk for salvage UDP-GlcNAc synthesis. 36747715 7 53 theme immunometabolic 1078:1092 arg1 mechanisms 1094:1103 potential immunometabolic mechanisms 1068:1103 potential immunometabolic mechanisms for a previously unappreciated set of these disorders 1068:1157 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 8 54 theme immunity 1188:1195 arg1 errors 1178:1183 Inborn errors 1171:1183 Inborn errors of immunity and metabolism 1171:1210 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 6 55 theme Mcl1 921:924 arg1 expression 926:935 Mcl1 expression 921:935 Mcl1 expression 921:935 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 8 56 theme metabolism 1201:1210 arg1 errors 1178:1183 Inborn errors 1171:1183 Inborn errors of immunity and metabolism 1171:1210 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 7 57 theme functional 1015:1024 arg1 degree 1005:1010 a high degree 998:1010 a high degree of functional overlap of IEM and IEI genes 998:1053 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 5 58 theme increased 764:772 arg1 Nagk 774:777 increased Nagk 764:777 increased Nagk for salvage UDP-GlcNAc synthesis 764:810 Interestingly, Gfpt1 -deficient T H 1 cells were more affected than T H 17 cells, which had increased Nagk for salvage UDP-GlcNAc synthesis. 36747715 5 59 contain had 760:762 arg1 which 754:758 which 754:758 which 754:758 Interestingly, Gfpt1 -deficient T H 1 cells were more affected than T H 17 cells, which had increased Nagk for salvage UDP-GlcNAc synthesis. 36747715 5 59 contain had 760:762 arg2 Nagk 774:777 increased Nagk 764:777 increased Nagk for salvage UDP-GlcNAc synthesis 764:810 Interestingly, Gfpt1 -deficient T H 1 cells were more affected than T H 17 cells, which had increased Nagk for salvage UDP-GlcNAc synthesis. 36747715 6 60 theme cell 889:892 arg1 activity 908:915 CD4 + T cell mitochondrial activity 881:915 CD4 + T cell mitochondrial activity 881:915 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 7 61 theme disorders 1149:1157 arg1 disorders 1149:1157 these disorders 1143:1157 these disorders 1143:1157 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 7 61 theme disorders 1149:1157 arg1 set 1136:1138 a previously unappreciated set 1109:1138 a previously unappreciated set of these disorders 1109:1157 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 1 62 theme Inborn 116:121 arg1 diseases 183:190 Mendelian diseases 173:190 Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations 173:268 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 1 62 theme Inborn 116:121 arg1 Errors 123:128 Inborn Errors 116:128 Inborn Errors of Metabolism (IEM) and Immunity (IEI) 116:167 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 8 63 theme known 1249:1253 arg1 deficiency 1261:1270 previously known Gfpt1 deficiency 1238:1270 previously known Gfpt1 deficiency 1238:1270 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 2 64 dep functional 351:360 arg1 overlap 362:368 overlap 362:368 overlap 362:368 Few genes are assigned to both IEM and IEI, but immunometabolic demands suggest functional overlap is underestimated. 36747715 0 65 theme Genes 63:67 arg1 Errors 29:34 Inborn Errors 22:34 Inborn Errors of Immunity and Metabolism Genes 22:67 Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities. 36747715 4 66 dep de 579:580 arg1 novo 582:585 novo 582:585 novo 582:585 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 5 67 theme T 704:704 arg1 cells 710:714 Gfpt1 -deficient T H 1 cells 687:714 Gfpt1 -deficient T H 1 cells 687:714 Interestingly, Gfpt1 -deficient T H 1 cells were more affected than T H 17 cells, which had increased Nagk for salvage UDP-GlcNAc synthesis. 36747715 0 68 theme T 76:76 arg1 Vulnerabilities 99:113 T Cell Immunometabolic Vulnerabilities 76:113 T Cell Immunometabolic Vulnerabilities 76:113 Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities. 36747715 0 69 theme Immunometabolic 83:97 arg1 Vulnerabilities 99:113 T Cell Immunometabolic Vulnerabilities 76:113 T Cell Immunometabolic Vulnerabilities 76:113 Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities. 36747715 2 70 dep suggest 343:349 arg1 underestimated 373:386 underestimated 373:386 suggest functional overlap is underestimated 343:386 Few genes are assigned to both IEM and IEI, but immunometabolic demands suggest functional overlap is underestimated. 36747715 6 71 theme necessary 937:945 arg1 activity 908:915 CD4 + T cell mitochondrial activity 881:915 CD4 + T cell mitochondrial activity 881:915 Screening IEI genes showed the transcription factor Bcl11b promotes CD4 + T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. 36747715 5 72 theme H 706:706 arg1 cells 710:714 Gfpt1 -deficient T H 1 cells 687:714 Gfpt1 -deficient T H 1 cells 687:714 Interestingly, Gfpt1 -deficient T H 1 cells were more affected than T H 17 cells, which had increased Nagk for salvage UDP-GlcNAc synthesis. 36747715 8 73 theme T 1317:1317 arg1 Loss 1336:1339 T cell subset fate Loss 1317:1339 T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI 1317:1380 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 7 74 theme unappreciated 1122:1134 arg1 disorders 1149:1157 these disorders 1143:1157 these disorders 1143:1157 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 7 74 theme unappreciated 1122:1134 arg1 set 1136:1138 a previously unappreciated set 1109:1138 a previously unappreciated set of these disorders 1109:1157 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 8 75 theme subset 1324:1329 arg1 Loss 1336:1339 T cell subset fate Loss 1317:1339 T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI 1317:1380 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 0 76 theme Inborn 22:27 arg1 Errors 29:34 Inborn Errors 22:34 Inborn Errors of Immunity and Metabolism Genes 22:67 Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities. 36747715 3 77 theme immunologic 437:447 arg1 roles 449:453 immunologic roles 437:453 immunologic roles 437:453 We applied CRISPR screens to test IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable crossover. 36747715 8 78 dep HIGHLIGHTS 1160:1169 arg1 have 1212:1215 have 1212:1215 have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms 1212:1497 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 8 79 theme Bcl11b 1344:1349 arg1 Loss 1336:1339 T cell subset fate Loss 1317:1339 T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI 1317:1380 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 7 80 theme potential 1068:1076 arg1 mechanisms 1094:1103 potential immunometabolic mechanisms 1068:1103 potential immunometabolic mechanisms for a previously unappreciated set of these disorders 1068:1157 These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders. 36747715 8 81 contain have 1433:1436 arg1 IEM 1425:1427 Many IEM 1420:1427 Many IEM 1420:1427 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 8 81 contain have 1433:1436 arg2 defects 1445:1451 immune defects 1438:1451 immune defects 1438:1451 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 4 82 dep cell 643:646 arg1 expansion 648:656 expansion 648:656 expansion 648:656 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 8 83 theme cell 1362:1365 arg1 IEI 1378:1380 a T cell deficiency IEI 1358:1380 a T cell deficiency IEI 1358:1380 HIGHLIGHTS Inborn errors of immunity and metabolism have greater overlap than previously known Gfpt1 deficiency causes an IEM but also selectively regulates T cell subset fate Loss of Bcl11b causes a T cell deficiency IEI but also harms mitochondrial function Many IEM may have immune defects and IEI may be driven by metabolic mechanisms. 36747715 1 84 theme complex 201:207 arg1 phenotypes 209:218 complex phenotypes 201:218 complex phenotypes 201:218 Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. 36747715 4 85 link N-linked 548:555 arg1 glycosylation 557:569 N-linked glycosylation 548:569 N-linked glycosylation 548:569 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 4 86 theme synthesis 598:606 arg1 Gfpt1 616:620 Gfpt1 616:620 Gfpt1 616:620 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 4 86 theme synthesis 598:606 arg1 critical 628:635 critical 628:635 critical 628:635 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 4 86 theme synthesis 598:606 arg1 enzyme 608:613 the de novo hexosamine synthesis enzyme 575:613 the de novo hexosamine synthesis enzyme 575:613 Analysis of IEM showed N-linked glycosylation and the de novo hexosamine synthesis enzyme, Gfpt1 , are critical for T cell expansion and function. 36747715 2 87 theme immunometabolic 319:333 arg1 demands 335:341 immunometabolic demands 319:341 immunometabolic demands 319:341 Few genes are assigned to both IEM and IEI, but immunometabolic demands suggest functional overlap is underestimated. 36610518 1 0 link N-linked 196:203 arg1 attribute 236:244 a critical quality attribute 217:244 a critical quality attribute due to their influence on activity and immunogenicity 217:298 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 1 0 link N-linked 196:203 arg1 glycans 205:211 N-linked glycans 196:211 N-linked glycans 196:211 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 5 1 theme glycosyltransferase 898:916 arg1 enzymes 918:924 glycosyltransferase enzymes 898:924 glycosyltransferase enzymes 898:924 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 1 2 gly glycoprotein 150:161 arg1 glycoprotein 150:161 glycoprotein therapeutics 150:174 glycoprotein therapeutics 150:174 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 6 3 used used 1067:1070 arg2 CHOGlycoNET 1048:1058 CHOGlycoNET 1048:1058 CHOGlycoNET 1048:1058 CHOGlycoNET can be used for accelerating glycomodel development and predicting the effect of glycoengineering strategies. 36610518 4 4 theme cell 679:682 arg1 lines 684:688 different CHO cell lines 665:688 different CHO cell lines 665:688 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 1 5 theme due 246:248 arg1 attribute 236:244 a critical quality attribute 217:244 a critical quality attribute due to their influence on activity and immunogenicity 217:298 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 1 5 theme due 246:248 arg1 glycans 205:211 N-linked glycans 196:211 N-linked glycans 196:211 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 1 6 dep production 136:145 arg1 proteins 176:183 proteins 176:183 proteins 176:183 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 3 7 theme cell 542:545 arg1 line 547:550 the cell line 538:550 the cell line 538:550 However, each study considers a unique glycosylation reaction network that is tailored around the cell line and product at hand. 36610518 4 8 theme native 644:649 arg1 proteins 651:658 native proteins 644:658 native proteins 644:658 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 1 9 theme ovary 89:93 arg1 cells 101:105 Chinese hamster ovary (CHO) cells 73:105 Chinese hamster ovary (CHO) cells 73:105 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 7 10 theme CHO 1273:1275 arg1 models 1295:1300 CHO cell genome scale models 1273:1300 CHO cell genome scale models 1273:1300 Finally, CHOGlycoNET is wrapped in a SBML file to be used as a standalone model or in combination with CHO cell genome scale models. 36610518 5 11 used used 842:845 arg2 CHOGlycoNET 827:837 CHOGlycoNET 827:837 CHOGlycoNET 827:837 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 3 12 theme unique 476:481 arg1 network 506:512 a unique glycosylation reaction network 474:512 a unique glycosylation reaction network that is tailored around the cell line and product at hand 474:570 However, each study considers a unique glycosylation reaction network that is tailored around the cell line and product at hand. 36610518 1 13 theme Chinese 73:79 arg1 cells 101:105 Chinese hamster ovary (CHO) cells 73:105 Chinese hamster ovary (CHO) cells 73:105 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 5 14 theme Golgi 933:937 arg1 apparatus 939:947 the Golgi apparatus 929:947 the Golgi apparatus 929:947 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 1 15 theme glycoprotein 150:161 arg1 therapeutics 163:174 glycoprotein therapeutics 150:174 glycoprotein therapeutics 150:174 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 5 16 theme enzymes 918:924 arg1 distribution 866:877 the distribution 862:877 the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus 862:947 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 1 17 theme hamster 81:87 arg1 cells 101:105 Chinese hamster ovary (CHO) cells 73:105 Chinese hamster ovary (CHO) cells 73:105 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 1 18 theme therapeutics 163:174 arg1 production 136:145 the production 132:145 the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity 132:298 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 5 19 theme dimensionality 1011:1024 arg1 reduction 1026:1034 dimensionality reduction 1011:1034 dimensionality reduction 1011:1034 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 1 20 from influence 259:267 arg1 activity 272:279 activity 272:279 activity 272:279 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 1 20 from influence 259:267 arg1 immunogenicity 285:298 immunogenicity 285:298 immunogenicity 285:298 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 7 21 theme genome 1282:1287 arg1 models 1295:1300 CHO cell genome scale models 1273:1300 CHO cell genome scale models 1273:1300 Finally, CHOGlycoNET is wrapped in a SBML file to be used as a standalone model or in combination with CHO cell genome scale models. 36610518 1 22 used used 123:126 arg2 cells 101:105 Chinese hamster ovary (CHO) cells 73:105 Chinese hamster ovary (CHO) cells 73:105 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 4 23 theme reaction 721:728 arg1 CHOGlycoNET 739:749 CHOGlycoNET 739:749 CHOGlycoNET 739:749 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 4 23 theme reaction 721:728 arg1 network 730:736 a comprehensive reaction network 705:736 a comprehensive reaction network 705:736 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 2 24 theme process 376:382 arg1 engineering 384:394 cell or process engineering 368:394 engineering 384:394 Manipulation of protein glycosylation is commonly achieved through cell or process engineering, which are often guided by mathematical models. 36610518 0 25 theme glycosylation 27:39 arg1 network 50:56 Comprehensive glycosylation reaction network 13:56 CHOGlycoNET: Comprehensive glycosylation reaction network for CHO cells. 0:71 CHOGlycoNET: Comprehensive glycosylation reaction network for CHO cells. 36610518 1 26 theme CHO 96:98 arg1 cells 101:105 Chinese hamster ovary (CHO) cells 73:105 Chinese hamster ovary (CHO) cells 73:105 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 6 27 theme glycomodel 1089:1098 arg1 development 1100:1110 glycomodel development 1089:1110 glycomodel development 1089:1110 CHOGlycoNET can be used for accelerating glycomodel development and predicting the effect of glycoengineering strategies. 36610518 0 28 theme Comprehensive 13:25 arg1 network 50:56 Comprehensive glycosylation reaction network 13:56 CHOGlycoNET: Comprehensive glycosylation reaction network for CHO cells. 0:71 CHOGlycoNET: Comprehensive glycosylation reaction network for CHO cells. 36610518 5 29 theme machine 990:996 arg1 learning 998:1005 machine learning 990:1005 machine learning 990:1005 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 5 30 theme network 966:972 arg1 reactions 974:982 key network reactions 962:982 key network reactions using machine learning and dimensionality reduction techniques 962:1045 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 5 31 theme mannosidase 882:892 arg1 distribution 866:877 the distribution 862:877 the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus 862:947 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 7 32 theme cell 1277:1280 arg1 models 1295:1300 CHO cell genome scale models 1273:1300 CHO cell genome scale models 1273:1300 Finally, CHOGlycoNET is wrapped in a SBML file to be used as a standalone model or in combination with CHO cell genome scale models. 36610518 7 33 with combination 1256:1266 arg1 models 1295:1300 CHO cell genome scale models 1273:1300 CHO cell genome scale models 1273:1300 Finally, CHOGlycoNET is wrapped in a SBML file to be used as a standalone model or in combination with CHO cell genome scale models. 36610518 1 34 theme N-linked 196:203 arg1 attribute 236:244 a critical quality attribute 217:244 a critical quality attribute due to their influence on activity and immunogenicity 217:298 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 1 34 theme N-linked 196:203 arg1 glycans 205:211 N-linked glycans 196:211 N-linked glycans 196:211 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 0 35 theme reaction 41:48 arg1 network 50:56 Comprehensive glycosylation reaction network 13:56 CHOGlycoNET: Comprehensive glycosylation reaction network for CHO cells. 0:71 CHOGlycoNET: Comprehensive glycosylation reaction network for CHO cells. 36610518 7 36 theme SBML 1207:1210 arg1 file 1212:1215 a SBML file 1205:1215 a SBML file to be used as a standalone model or in combination with CHO cell genome scale models 1205:1300 Finally, CHOGlycoNET is wrapped in a SBML file to be used as a standalone model or in combination with CHO cell genome scale models. 36610518 0 37 theme CHO 62:64 arg1 cells 66:70 CHO cells 62:70 CHO cells 62:70 CHOGlycoNET: Comprehensive glycosylation reaction network for CHO cells. 36610518 4 38 theme glycan 592:597 arg1 datasets 599:606 200 glycan datasets 588:606 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines 588:688 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 3 39 theme glycosylation 483:495 arg1 network 506:512 a unique glycosylation reaction network 474:512 a unique glycosylation reaction network that is tailored around the cell line and product at hand 474:570 However, each study considers a unique glycosylation reaction network that is tailored around the cell line and product at hand. 36610518 7 40 theme standalone 1233:1242 arg1 model 1244:1248 a standalone model 1231:1248 a standalone model 1231:1248 Finally, CHOGlycoNET is wrapped in a SBML file to be used as a standalone model or in combination with CHO cell genome scale models. 36610518 3 41 theme reaction 497:504 arg1 network 506:512 a unique glycosylation reaction network 474:512 a unique glycosylation reaction network that is tailored around the cell line and product at hand 474:570 However, each study considers a unique glycosylation reaction network that is tailored around the cell line and product at hand. 36610518 4 42 theme reaction 784:791 arg1 networks 793:800 the individual minimal reaction networks 761:800 the individual minimal reaction networks describing each dataset 761:824 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 4 43 theme minimal 776:782 arg1 networks 793:800 the individual minimal reaction networks 761:800 the individual minimal reaction networks describing each dataset 761:824 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 4 44 theme different 665:673 arg1 lines 684:688 different CHO cell lines 665:688 different CHO cell lines 665:688 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 2 45 theme glycosylation 325:337 arg1 Manipulation 301:312 Manipulation 301:312 Manipulation of protein glycosylation 301:337 Manipulation of protein glycosylation is commonly achieved through cell or process engineering, which are often guided by mathematical models. 36610518 5 46 theme key 962:964 arg1 reactions 974:982 key network reactions 962:982 key network reactions using machine learning and dimensionality reduction techniques 962:1045 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 5 47 theme learning 998:1005 arg1 techniques 1036:1045 machine learning and dimensionality reduction techniques 990:1045 machine learning and dimensionality reduction techniques 990:1045 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 4 48 theme individual 765:774 arg1 networks 793:800 the individual minimal reaction networks 761:800 the individual minimal reaction networks describing each dataset 761:824 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 5 49 from distribution 866:877 arg1 apparatus 939:947 the Golgi apparatus 929:947 the Golgi apparatus 929:947 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 2 50 theme protein 317:323 arg1 glycosylation 325:337 protein glycosylation 317:337 protein glycosylation 317:337 Manipulation of protein glycosylation is commonly achieved through cell or process engineering, which are often guided by mathematical models. 36610518 4 51 theme comprehensive 707:719 arg1 CHOGlycoNET 739:749 CHOGlycoNET 739:749 CHOGlycoNET 739:749 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 4 51 theme comprehensive 707:719 arg1 network 730:736 a comprehensive reaction network 705:736 a comprehensive reaction network 705:736 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 6 52 theme glycoengineering 1141:1156 arg1 strategies 1158:1167 glycoengineering strategies 1141:1167 glycoengineering strategies 1141:1167 CHOGlycoNET can be used for accelerating glycomodel development and predicting the effect of glycoengineering strategies. 36610518 5 53 theme reduction 1026:1034 arg1 techniques 1036:1045 machine learning and dimensionality reduction techniques 990:1045 machine learning and dimensionality reduction techniques 990:1045 CHOGlycoNET is used to investigate the distribution of mannosidase and glycosyltransferase enzymes in the Golgi apparatus and identify key network reactions using machine learning and dimensionality reduction techniques. 36610518 2 54 theme mathematical 423:434 arg1 models 436:441 mathematical models 423:441 mathematical models 423:441 Manipulation of protein glycosylation is commonly achieved through cell or process engineering, which are often guided by mathematical models. 36610518 4 55 theme CHO 675:677 arg1 lines 684:688 different CHO cell lines 665:688 different CHO cell lines 665:688 Herein, we use 200 glycan datasets for both recombinantly produced and native proteins from different CHO cell lines to reconstruct a comprehensive reaction network, CHOGlycoNET, based on the individual minimal reaction networks describing each dataset. 36610518 1 56 theme critical 219:226 arg1 attribute 236:244 a critical quality attribute 217:244 a critical quality attribute due to their influence on activity and immunogenicity 217:298 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 1 56 theme critical 219:226 arg1 glycans 205:211 N-linked glycans 196:211 N-linked glycans 196:211 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 6 57 theme strategies 1158:1167 arg1 effect 1131:1136 the effect 1127:1136 the effect of glycoengineering strategies 1127:1167 CHOGlycoNET can be used for accelerating glycomodel development and predicting the effect of glycoengineering strategies. 36610518 0 58 dep CHOGlycoNET 0:10 arg1 network 50:56 Comprehensive glycosylation reaction network 13:56 CHOGlycoNET: Comprehensive glycosylation reaction network for CHO cells. 0:71 CHOGlycoNET: Comprehensive glycosylation reaction network for CHO cells. 36610518 7 59 theme scale 1289:1293 arg1 models 1295:1300 CHO cell genome scale models 1273:1300 CHO cell genome scale models 1273:1300 Finally, CHOGlycoNET is wrapped in a SBML file to be used as a standalone model or in combination with CHO cell genome scale models. 36610518 2 60 theme cell 368:371 arg1 engineering 384:394 cell or process engineering 368:394 engineering 384:394 Manipulation of protein glycosylation is commonly achieved through cell or process engineering, which are often guided by mathematical models. 36610518 1 61 theme quality 228:234 arg1 attribute 236:244 a critical quality attribute 217:244 a critical quality attribute due to their influence on activity and immunogenicity 217:298 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36610518 1 61 theme quality 228:234 arg1 glycans 205:211 N-linked glycans 196:211 N-linked glycans 196:211 Chinese hamster ovary (CHO) cells are extensively used for the production of glycoprotein therapeutics proteins, for which N-linked glycans are a critical quality attribute due to their influence on activity and immunogenicity. 36149962 0 0 theme viral 91:95 arg1 infectivity 97:107 viral infectivity 91:107 viral infectivity 91:107 Role for N-glycans and calnexin-calreticulin chaperones in SARS-CoV-2 Spike maturation and viral infectivity. 36149962 5 1 theme glycan 708:713 arg1 mutations 715:723 glycan mutations 708:723 glycan mutations 708:723 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 7 2 theme calnexin 1045:1052 arg1 KOs 1054:1056 calnexin KOs 1045:1056 calnexin KOs 1045:1056 Here, while both chaperones regulated pseudovirus function, only VLPs produced in calnexin KOs were less infectious. 36149962 4 3 theme ACE2-expressing 659:673 arg1 cells 675:679 ACE2-expressing cells 659:679 ACE2-expressing cells 659:679 These mutations also reduced pseudovirus and VLP entry into ACE2-expressing cells by 80 to 90%. 36149962 2 4 gly N-glycosylation 308:322 arg2 sites 324:328 N-glycosylation sites 308:328 N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites 308:426 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 5 5 theme formation 819:827 arg1 expression 771:780 cell surface expression 758:780 cell surface expression of Spike, ACE2 binding, and syncytia formation 758:827 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 0 6 from Role 0:3 arg1 maturation 76:85 SARS-CoV-2 Spike maturation 59:85 SARS-CoV-2 Spike maturation 59:85 Role for N-glycans and calnexin-calreticulin chaperones in SARS-CoV-2 Spike maturation and viral infectivity. 36149962 0 6 from Role 0:3 arg1 infectivity 97:107 viral infectivity 91:107 viral infectivity 91:107 Role for N-glycans and calnexin-calreticulin chaperones in SARS-CoV-2 Spike maturation and viral infectivity. 36149962 3 7 theme lentivirus 534:543 arg1 particles 581:589 Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles 516:589 Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs) 516:596 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 3 7 theme lentivirus 534:543 arg1 VLPs 592:595 VLPs 592:595 VLPs 592:595 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 2 8 theme mutations 295:303 arg1 panel 279:283 a panel 277:283 a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites 277:426 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 2 9 from sites 324:328 arg1 panel 279:283 a panel 277:283 a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites 277:426 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 2 9 from sites 324:328 arg1 mutations 295:303 N-to-Q mutations 288:303 N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites 288:426 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 3 10 theme Spike 491:495 arg1 incorporation 497:509 Spike incorporation 491:509 Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs) 491:596 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 2 11 theme N-to-Q 288:293 arg1 mutations 295:303 N-to-Q mutations 288:303 N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites 288:426 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 5 12 theme ACE2 792:795 arg1 binding 797:803 ACE2 binding 792:803 ACE2 binding 792:803 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 1 13 from glycans 168:174 arg1 protein 200:206 the SARS-CoV-2 Spike protein 179:206 the SARS-CoV-2 Spike protein 179:206 Functional and epidemiological data suggest that N-linked glycans on the SARS-CoV-2 Spike protein may contribute to viral infectivity. 36149962 1 14 theme SARS-CoV-2 183:192 arg1 protein 200:206 the SARS-CoV-2 Spike protein 179:206 the SARS-CoV-2 Spike protein 179:206 Functional and epidemiological data suggest that N-linked glycans on the SARS-CoV-2 Spike protein may contribute to viral infectivity. 36149962 8 15 theme Spike 1089:1093 arg1 targets 1173:1179 drug targets 1168:1179 drug targets for COVID-19 1168:1192 Overall, Spike N-glycans are likely critical for SARS-CoV-2 function and could serve as drug targets for COVID-19. 36149962 8 15 theme Spike 1089:1093 arg1 N-glycans 1095:1103 Spike N-glycans 1089:1103 Spike N-glycans 1089:1103 Overall, Spike N-glycans are likely critical for SARS-CoV-2 function and could serve as drug targets for COVID-19. 36149962 1 16 theme Spike 194:198 arg1 protein 200:206 the SARS-CoV-2 Spike protein 179:206 the SARS-CoV-2 Spike protein 179:206 Functional and epidemiological data suggest that N-linked glycans on the SARS-CoV-2 Spike protein may contribute to viral infectivity. 36149962 2 17 theme proximal 330:337 arg1 sites 324:328 N-glycosylation sites 308:328 N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites 308:426 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 6 18 theme host 902:905 arg1 cells 907:911 host cells 902:911 host cells lacking ER chaperones, calnexin and calreticulin 902:960 A similar dichotomy in function was observed when virus was produced in host cells lacking ER chaperones, calnexin and calreticulin. 36149962 3 19 theme Spike-pseudotyped 516:532 arg1 particles 581:589 Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles 516:589 Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs) 516:596 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 3 19 theme Spike-pseudotyped 516:532 arg1 VLPs 592:595 VLPs 592:595 VLPs 592:595 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 8 20 theme drug 1168:1171 arg1 targets 1173:1179 drug targets 1168:1179 drug targets for COVID-19 1168:1192 Overall, Spike N-glycans are likely critical for SARS-CoV-2 function and could serve as drug targets for COVID-19. 36149962 8 20 theme drug 1168:1171 arg1 N-glycans 1095:1103 Spike N-glycans 1089:1103 Spike N-glycans 1089:1103 Overall, Spike N-glycans are likely critical for SARS-CoV-2 function and could serve as drug targets for COVID-19. 36149962 5 21 theme cell 758:761 arg1 expression 771:780 cell surface expression 758:780 cell surface expression of Spike, ACE2 binding, and syncytia formation 758:827 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 2 22 theme N-glycosylation 308:322 arg1 sites 324:328 N-glycosylation sites 308:328 N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites 308:426 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 0 23 theme N-glycans 9:17 arg1 chaperones 45:54 N-glycans and calnexin-calreticulin chaperones 9:54 N-glycans and calnexin-calreticulin chaperones 9:54 Role for N-glycans and calnexin-calreticulin chaperones in SARS-CoV-2 Spike maturation and viral infectivity. 36149962 7 24 theme pseudovirus 1001:1011 arg1 function 1013:1020 pseudovirus function 1001:1020 pseudovirus function 1001:1020 Here, while both chaperones regulated pseudovirus function, only VLPs produced in calnexin KOs were less infectious. 36149962 5 25 theme syncytia 810:817 arg1 formation 819:827 syncytia formation 810:827 syncytia formation 810:827 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 1 26 link N-linked 159:166 arg1 glycans 168:174 N-linked glycans 159:174 N-linked glycans on the SARS-CoV-2 Spike protein 159:206 Functional and epidemiological data suggest that N-linked glycans on the SARS-CoV-2 Spike protein may contribute to viral infectivity. 36149962 5 27 theme Spike 785:789 arg1 expression 771:780 cell surface expression 758:780 cell surface expression of Spike, ACE2 binding, and syncytia formation 758:827 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 3 28 theme authentic 549:557 arg1 particles 581:589 Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles 516:589 Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs) 516:596 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 3 28 theme authentic 549:557 arg1 VLPs 592:595 VLPs 592:595 VLPs 592:595 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 1 29 theme viral 226:230 arg1 infectivity 232:242 viral infectivity 226:242 viral infectivity 226:242 Functional and epidemiological data suggest that N-linked glycans on the SARS-CoV-2 Spike protein may contribute to viral infectivity. 36149962 2 30 theme proteolysis 410:420 arg1 sites 422:426 proteolysis sites 410:426 proteolysis sites 410:426 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 5 31 theme binding 797:803 arg1 expression 771:780 cell surface expression 758:780 cell surface expression of Spike, ACE2 binding, and syncytia formation 758:827 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 0 32 theme calnexin-calreticulin 23:43 arg1 chaperones 45:54 N-glycans and calnexin-calreticulin chaperones 9:54 N-glycans and calnexin-calreticulin chaperones 9:54 Role for N-glycans and calnexin-calreticulin chaperones in SARS-CoV-2 Spike maturation and viral infectivity. 36149962 6 33 theme ER 921:922 arg1 calnexin 936:943 calnexin 936:943 calnexin 936:943 A similar dichotomy in function was observed when virus was produced in host cells lacking ER chaperones, calnexin and calreticulin. 36149962 6 33 theme ER 921:922 arg1 chaperones 924:933 ER chaperones 921:933 ER chaperones 921:933 A similar dichotomy in function was observed when virus was produced in host cells lacking ER chaperones, calnexin and calreticulin. 36149962 6 33 theme ER 921:922 arg1 calreticulin 949:960 calreticulin 949:960 calreticulin 949:960 A similar dichotomy in function was observed when virus was produced in host cells lacking ER chaperones, calnexin and calreticulin. 36149962 3 34 theme SARS-CoV-2 559:568 arg1 particles 581:589 Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles 516:589 Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs) 516:596 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 3 34 theme SARS-CoV-2 559:568 arg1 VLPs 592:595 VLPs 592:595 VLPs 592:595 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 0 35 theme SARS-CoV-2 59:68 arg1 maturation 76:85 SARS-CoV-2 Spike maturation 59:85 SARS-CoV-2 Spike maturation 59:85 Role for N-glycans and calnexin-calreticulin chaperones in SARS-CoV-2 Spike maturation and viral infectivity. 36149962 8 36 theme SARS-CoV-2 1129:1138 arg1 function 1140:1147 SARS-CoV-2 function 1129:1147 SARS-CoV-2 function 1129:1147 Overall, Spike N-glycans are likely critical for SARS-CoV-2 function and could serve as drug targets for COVID-19. 36149962 2 37 dep S2 390:391 arg1 N603 395:398 N603 395:398 N603 395:398 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 2 37 dep S2 390:391 arg1 N801 404:407 N801 404:407 N801 404:407 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 1 38 theme epidemiological 125:139 arg1 data 141:144 Functional and epidemiological data 110:144 Functional and epidemiological data 110:144 Functional and epidemiological data suggest that N-linked glycans on the SARS-CoV-2 Spike protein may contribute to viral infectivity. 36149962 5 39 theme minor 742:746 arg1 effect 748:753 a relatively minor effect 729:753 a relatively minor effect 729:753 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 2 40 theme Spike 346:350 arg1 S1-S2 352:356 the Spike S1-S2 342:356 the Spike S1-S2 (N61, N603, N657, and N616) 342:384 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 2 41 dep S1-S2 352:356 arg1 N61 359:361 N61 359:361 N61 359:361 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 2 41 dep S1-S2 352:356 arg1 sites 422:426 proteolysis sites 410:426 proteolysis sites 410:426 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 2 41 dep S1-S2 352:356 arg1 N657 370:373 N657 370:373 N657 370:373 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 2 41 dep S1-S2 352:356 arg1 N616 380:383 N616 380:383 N616 380:383 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 2 41 dep S1-S2 352:356 arg1 N603 364:367 N603 364:367 N603 364:367 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 1 42 theme Functional 110:119 arg1 data 141:144 Functional and epidemiological data 110:144 Functional and epidemiological data 110:144 Functional and epidemiological data suggest that N-linked glycans on the SARS-CoV-2 Spike protein may contribute to viral infectivity. 36149962 4 43 dep 90 690:691 arg1 to 687:688 to 687:688 to 687:688 These mutations also reduced pseudovirus and VLP entry into ACE2-expressing cells by 80 to 90%. 36149962 6 44 from dichotomy 840:848 arg1 function 853:860 function 853:860 function 853:860 A similar dichotomy in function was observed when virus was produced in host cells lacking ER chaperones, calnexin and calreticulin. 36149962 5 45 contain had 725:727 arg2 effect 748:753 a relatively minor effect 729:753 a relatively minor effect 729:753 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 5 45 contain had 725:727 arg1 mutations 715:723 glycan mutations 708:723 glycan mutations 708:723 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 3 46 theme virus-like 570:579 arg1 particles 581:589 Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles 516:589 Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs) 516:596 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 3 46 theme virus-like 570:579 arg1 VLPs 592:595 VLPs 592:595 VLPs 592:595 Some of these mutations, particularly N61Q and N801Q, reduced Spike incorporation into Spike-pseudotyped lentivirus and authentic SARS-CoV-2 virus-like particles (VLPs). 36149962 1 47 theme N-linked 159:166 arg1 glycans 168:174 N-linked glycans 159:174 N-linked glycans on the SARS-CoV-2 Spike protein 159:206 Functional and epidemiological data suggest that N-linked glycans on the SARS-CoV-2 Spike protein may contribute to viral infectivity. 36149962 2 48 from panel 279:283 arg1 sites 324:328 N-glycosylation sites 308:328 N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites 308:426 To investigate this, we created a panel of N-to-Q mutations at N-glycosylation sites proximal to the Spike S1-S2 (N61, N603, N657, and N616) and S2' (N603 and N801) proteolysis sites. 36149962 6 49 theme similar 832:838 arg1 dichotomy 840:848 A similar dichotomy 830:848 A similar dichotomy in function 830:860 A similar dichotomy in function was observed when virus was produced in host cells lacking ER chaperones, calnexin and calreticulin. 36149962 0 50 theme Spike 70:74 arg1 maturation 76:85 SARS-CoV-2 Spike maturation 59:85 SARS-CoV-2 Spike maturation 59:85 Role for N-glycans and calnexin-calreticulin chaperones in SARS-CoV-2 Spike maturation and viral infectivity. 36149962 5 51 theme surface 763:769 arg1 expression 771:780 cell surface expression 758:780 cell surface expression of Spike, ACE2 binding, and syncytia formation 758:827 In contrast, glycan mutations had a relatively minor effect on cell surface expression of Spike, ACE2 binding, and syncytia formation. 36149962 4 52 theme VLP 644:646 arg1 entry 648:652 VLP entry 644:652 VLP entry 644:652 These mutations also reduced pseudovirus and VLP entry into ACE2-expressing cells by 80 to 90%. 35637269 0 0 theme congenital 76:85 arg1 disorders 87:95 congenital disorders 76:95 congenital disorders of glycosylation 76:112 Compound heterozygous variants in MAN2B2 identified in a Chinese child with congenital disorders of glycosylation. 35637269 0 1 from variants 22:29 arg1 MAN2B2 34:39 MAN2B2 34:39 MAN2B2 34:39 Compound heterozygous variants in MAN2B2 identified in a Chinese child with congenital disorders of glycosylation. 35637269 8 2 theme mass 846:849 arg1 spectrometry 851:862 time-of-flight mass spectrometry 831:862 time-of-flight mass spectrometry (MALDI-TOF MS) 831:877 Serum N-glycan profiling was measured by MALDI coupled to time-of-flight mass spectrometry (MALDI-TOF MS). 35637269 8 2 theme mass 846:849 arg1 MS 875:876 MALDI-TOF MS 865:876 MALDI-TOF MS 865:876 Serum N-glycan profiling was measured by MALDI coupled to time-of-flight mass spectrometry (MALDI-TOF MS). 35637269 7 3 theme proband 718:724 arg1 presentations 695:707 the clinical presentations 682:707 the clinical presentations of a CDG proband with compound heterozygous variants in MAN2B2 682:770 In this study, we described the clinical presentations of a CDG proband with compound heterozygous variants in MAN2B2. 35637269 10 4 theme facial 1098:1103 arg1 features 1105:1112 dysmorphic facial features 1087:1112 dysmorphic facial features as in the previous case 1087:1136 Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. 35637269 10 4 theme facial 1098:1103 arg1 delay 1080:1084 severe developmental delay 1059:1084 severe developmental delay 1059:1084 Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. 35637269 8 5 theme MALDI-TOF 865:873 arg1 spectrometry 851:862 time-of-flight mass spectrometry 831:862 time-of-flight mass spectrometry (MALDI-TOF MS) 831:877 Serum N-glycan profiling was measured by MALDI coupled to time-of-flight mass spectrometry (MALDI-TOF MS). 35637269 8 5 theme MALDI-TOF 865:873 arg1 MS 875:876 MALDI-TOF MS 865:876 MALDI-TOF MS 865:876 Serum N-glycan profiling was measured by MALDI coupled to time-of-flight mass spectrometry (MALDI-TOF MS). 35637269 12 6 from role 1353:1356 arg1 CDG 1376:1378 CDG 1376:1378 CDG 1376:1378 Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG. 35637269 9 7 theme N-linked 939:946 arg1 glycosylation 948:960 N-linked glycosylation 939:960 N-linked glycosylation 939:960 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 10 8 theme dysmorphic 1087:1096 arg1 features 1105:1112 dysmorphic facial features 1087:1112 dysmorphic facial features as in the previous case 1087:1136 Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. 35637269 10 8 theme dysmorphic 1087:1096 arg1 delay 1080:1084 severe developmental delay 1059:1084 severe developmental delay 1059:1084 Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. 35637269 5 9 theme representative 411:424 arg1 features 435:442 The representative clinical features 407:442 The representative clinical features 407:442 The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. 35637269 5 9 theme representative 411:424 arg1 deficiency 456:465 immune deficiency 449:465 immune deficiency 449:465 The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. 35637269 9 10 theme glycosylation 948:960 arg1 disorders 926:934 disorders 926:934 disorders 926:934 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 9 10 theme glycosylation 948:960 arg1 N-glycans 983:991 increased N-glycans 973:991 increased N-glycans 973:991 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 9 10 theme glycosylation 948:960 arg1 value 1030:1034 elevated Man5/Man6 and Man5/Man9 value 997:1034 elevated Man5/Man6 and Man5/Man9 value 997:1034 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 0 11 with child 65:69 arg1 disorders 87:95 congenital disorders 76:95 congenital disorders of glycosylation 76:112 Compound heterozygous variants in MAN2B2 identified in a Chinese child with congenital disorders of glycosylation. 35637269 3 12 theme MAN2B2 328:333 arg1 gene 335:338 the MAN2B2 gene 324:338 the MAN2B2 gene 324:338 MAN2B2-CDG caused by pathogenic variants in the MAN2B2 gene was a rare CDG. 35637269 7 13 theme CDG 714:716 arg1 proband 718:724 a CDG proband 712:724 a CDG proband 712:724 In this study, we described the clinical presentations of a CDG proband with compound heterozygous variants in MAN2B2. 35637269 3 14 theme rare 346:349 arg1 CDG 351:353 a rare CDG 344:353 a rare CDG 344:353 MAN2B2-CDG caused by pathogenic variants in the MAN2B2 gene was a rare CDG. 35637269 3 14 theme rare 346:349 arg1 MAN2B2-CDG 280:289 MAN2B2-CDG 280:289 MAN2B2-CDG caused by pathogenic variants in the MAN2B2 gene 280:338 MAN2B2-CDG caused by pathogenic variants in the MAN2B2 gene was a rare CDG. 35637269 10 15 theme previous 1124:1131 arg1 case 1133:1136 the previous case 1120:1136 the previous case 1120:1136 Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. 35637269 8 16 theme Serum 773:777 arg1 profiling 788:796 Serum N-glycan profiling 773:796 Serum N-glycan profiling 773:796 Serum N-glycan profiling was measured by MALDI coupled to time-of-flight mass spectrometry (MALDI-TOF MS). 35637269 4 17 theme MAN2B2-CDG 382:391 arg1 case 374:377 only one case 365:377 only one case of MAN2B2-CDG 365:391 To date, only one case of MAN2B2-CDG was reported. 35637269 9 18 link N-linked 939:946 arg1 glycosylation 948:960 N-linked glycosylation 939:960 N-linked glycosylation 939:960 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 0 19 theme glycosylation 100:112 arg1 disorders 87:95 congenital disorders 76:95 congenital disorders of glycosylation 76:112 Compound heterozygous variants in MAN2B2 identified in a Chinese child with congenital disorders of glycosylation. 35637269 6 20 theme MAN2B2 595:600 arg1 variation 602:610 MAN2B2 variation 595:610 MAN2B2 variation 595:610 More cases are needed to support the pathogenesis of MAN2B2 variation and elucidate its clinical heterogeneity. 35637269 1 21 theme group 164:168 arg1 disorders 180:188 a group inherited disorders 162:188 a group inherited disorders 162:188 Congenital disorders of glycosylation (CDG) is a group inherited disorders. 35637269 0 22 theme heterozygous 9:20 arg1 variants 22:29 Compound heterozygous variants 0:29 Compound heterozygous variants in MAN2B2 0:39 Compound heterozygous variants in MAN2B2 identified in a Chinese child with congenital disorders of glycosylation. 35637269 1 23 theme inherited 170:178 arg1 disorders 180:188 a group inherited disorders 162:188 a group inherited disorders 162:188 Congenital disorders of glycosylation (CDG) is a group inherited disorders. 35637269 0 24 theme Compound 0:7 arg1 variants 22:29 Compound heterozygous variants 0:29 Compound heterozygous variants in MAN2B2 0:39 Compound heterozygous variants in MAN2B2 identified in a Chinese child with congenital disorders of glycosylation. 35637269 11 25 theme immune 1223:1228 arg1 deficiency 1230:1239 no immune deficiency 1220:1239 no immune deficiency 1220:1239 But our case presented new features, including cleft palate and hypospadias with no immune deficiency. 35637269 11 26 theme cleft 1186:1190 arg1 palate 1192:1197 cleft palate 1186:1197 cleft palate 1186:1197 But our case presented new features, including cleft palate and hypospadias with no immune deficiency. 35637269 6 27 theme More 542:545 arg1 cases 547:551 More cases 542:551 More cases 542:551 More cases are needed to support the pathogenesis of MAN2B2 variation and elucidate its clinical heterogeneity. 35637269 9 28 theme elevated 997:1004 arg1 value 1030:1034 elevated Man5/Man6 and Man5/Man9 value 997:1034 elevated Man5/Man6 and Man5/Man9 value 997:1034 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 10 29 from features 1105:1112 arg1 case 1133:1136 the previous case 1120:1136 the previous case 1120:1136 Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. 35637269 12 30 from CDG 1376:1378 arg1 importance 1335:1344 the importance 1331:1344 the importance of the role of MAN2B2 gene in CDG 1331:1378 Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG. 35637269 5 31 theme dysmorphic 468:477 arg1 features 486:493 dysmorphic facial features 468:493 dysmorphic facial features 468:493 The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. 35637269 9 32 theme Man5/Man6 1006:1014 arg1 value 1030:1034 elevated Man5/Man6 and Man5/Man9 value 997:1034 elevated Man5/Man6 and Man5/Man9 value 997:1034 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 2 33 with dysfunction 226:236 arg1 morbidity 255:263 significant morbidity 243:263 significant morbidity 243:263 It is characterized by multi-organ dysfunction with significant morbidity and mortality. 35637269 2 33 with dysfunction 226:236 arg1 mortality 269:277 mortality 269:277 mortality 269:277 It is characterized by multi-organ dysfunction with significant morbidity and mortality. 35637269 12 34 from importance 1335:1344 arg1 CDG 1376:1378 CDG 1376:1378 CDG 1376:1378 Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG. 35637269 12 35 theme MAN2B2 1361:1366 arg1 gene 1368:1371 MAN2B2 gene 1361:1371 MAN2B2 gene 1361:1371 Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG. 35637269 5 36 theme facial 479:484 arg1 features 486:493 dysmorphic facial features 468:493 dysmorphic facial features 468:493 The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. 35637269 12 37 theme clinical 1282:1289 arg1 phenotypes 1291:1300 both the molecular and clinical phenotypes 1259:1300 phenotypes 1291:1300 Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG. 35637269 9 38 theme MALDI-TOF 880:888 arg1 analysis 893:900 MALDI-TOF MS analysis 880:900 MALDI-TOF MS analysis of patient serum 880:917 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 8 39 theme N-glycan 779:786 arg1 profiling 788:796 Serum N-glycan profiling 773:796 Serum N-glycan profiling 773:796 Serum N-glycan profiling was measured by MALDI coupled to time-of-flight mass spectrometry (MALDI-TOF MS). 35637269 9 40 theme Man5/Man9 1020:1028 arg1 value 1030:1034 elevated Man5/Man6 and Man5/Man9 value 997:1034 elevated Man5/Man6 and Man5/Man9 value 997:1034 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 9 41 theme MS 890:891 arg1 analysis 893:900 MALDI-TOF MS analysis 880:900 MALDI-TOF MS analysis of patient serum 880:917 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 7 42 theme clinical 686:693 arg1 presentations 695:707 the clinical presentations 682:707 the clinical presentations of a CDG proband with compound heterozygous variants in MAN2B2 682:770 In this study, we described the clinical presentations of a CDG proband with compound heterozygous variants in MAN2B2. 35637269 2 43 theme multi-organ 214:224 arg1 dysfunction 226:236 multi-organ dysfunction 214:236 multi-organ dysfunction with significant morbidity and mortality 214:277 It is characterized by multi-organ dysfunction with significant morbidity and mortality. 35637269 7 44 from variants 753:760 arg1 MAN2B2 765:770 MAN2B2 765:770 MAN2B2 765:770 In this study, we described the clinical presentations of a CDG proband with compound heterozygous variants in MAN2B2. 35637269 1 45 theme Congenital 115:124 arg1 disorders 126:134 Congenital disorders 115:134 Congenital disorders of glycosylation (CDG) 115:157 Congenital disorders of glycosylation (CDG) is a group inherited disorders. 35637269 9 46 theme increased 973:981 arg1 N-glycans 983:991 increased N-glycans 973:991 increased N-glycans 973:991 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 12 47 theme MAN2B2-CDG 1305:1314 arg1 phenotypes 1291:1300 both the molecular and clinical phenotypes 1259:1300 phenotypes 1291:1300 Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG. 35637269 12 48 theme gene 1368:1371 arg1 role 1353:1356 the role 1349:1356 the role of MAN2B2 gene in CDG 1349:1378 Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG. 35637269 5 49 theme clinical 426:433 arg1 features 435:442 The representative clinical features 407:442 The representative clinical features 407:442 The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. 35637269 5 49 theme clinical 426:433 arg1 deficiency 456:465 immune deficiency 449:465 immune deficiency 449:465 The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. 35637269 11 50 theme new 1162:1164 arg1 palate 1192:1197 cleft palate 1186:1197 cleft palate 1186:1197 But our case presented new features, including cleft palate and hypospadias with no immune deficiency. 35637269 11 50 theme new 1162:1164 arg1 features 1166:1173 new features 1162:1173 new features 1162:1173 But our case presented new features, including cleft palate and hypospadias with no immune deficiency. 35637269 11 50 theme new 1162:1164 arg1 hypospadias 1203:1213 hypospadias 1203:1213 hypospadias 1203:1213 But our case presented new features, including cleft palate and hypospadias with no immune deficiency. 35637269 3 51 theme pathogenic 301:310 arg1 variants 312:319 pathogenic variants 301:319 pathogenic variants in the MAN2B2 gene 301:338 MAN2B2-CDG caused by pathogenic variants in the MAN2B2 gene was a rare CDG. 35637269 12 52 dep phenotypes 1291:1300 arg1 both 1259:1262 both 1259:1262 both 1259:1262 Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG. 35637269 12 53 theme molecular 1268:1276 arg1 phenotypes 1291:1300 both the molecular and clinical phenotypes 1259:1300 phenotypes 1291:1300 Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG. 35637269 7 54 with presentations 695:707 arg1 variants 753:760 compound heterozygous variants 731:760 compound heterozygous variants in MAN2B2 731:770 In this study, we described the clinical presentations of a CDG proband with compound heterozygous variants in MAN2B2. 35637269 9 55 theme patient 905:911 arg1 serum 913:917 patient serum 905:917 patient serum 905:917 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 10 56 theme developmental 1066:1078 arg1 features 1105:1112 dysmorphic facial features 1087:1112 dysmorphic facial features as in the previous case 1087:1136 Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. 35637269 10 56 theme developmental 1066:1078 arg1 delay 1080:1084 severe developmental delay 1059:1084 severe developmental delay 1059:1084 Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. 35637269 1 57 theme glycosylation 139:151 arg1 disorders 126:134 Congenital disorders 115:134 Congenital disorders of glycosylation (CDG) 115:157 Congenital disorders of glycosylation (CDG) is a group inherited disorders. 35637269 8 58 theme time-of-flight 831:844 arg1 spectrometry 851:862 time-of-flight mass spectrometry 831:862 time-of-flight mass spectrometry (MALDI-TOF MS) 831:877 Serum N-glycan profiling was measured by MALDI coupled to time-of-flight mass spectrometry (MALDI-TOF MS). 35637269 8 58 theme time-of-flight 831:844 arg1 MS 875:876 MALDI-TOF MS 865:876 MALDI-TOF MS 865:876 Serum N-glycan profiling was measured by MALDI coupled to time-of-flight mass spectrometry (MALDI-TOF MS). 35637269 3 59 from variants 312:319 arg1 gene 335:338 the MAN2B2 gene 324:338 the MAN2B2 gene 324:338 MAN2B2-CDG caused by pathogenic variants in the MAN2B2 gene was a rare CDG. 35637269 9 60 theme serum 913:917 arg1 analysis 893:900 MALDI-TOF MS analysis 880:900 MALDI-TOF MS analysis of patient serum 880:917 MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. 35637269 10 61 theme severe 1059:1064 arg1 features 1105:1112 dysmorphic facial features 1087:1112 dysmorphic facial features as in the previous case 1087:1136 Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. 35637269 10 61 theme severe 1059:1064 arg1 delay 1080:1084 severe developmental delay 1059:1084 severe developmental delay 1059:1084 Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. 35637269 12 62 theme role 1353:1356 arg1 importance 1335:1344 the importance 1331:1344 the importance of the role of MAN2B2 gene in CDG 1331:1378 Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG. 35637269 5 63 theme severe 514:519 arg1 delay 535:539 severe developmental delay 514:539 severe developmental delay 514:539 The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. 35637269 5 64 theme immune 449:454 arg1 features 435:442 The representative clinical features 407:442 The representative clinical features 407:442 The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. 35637269 5 64 theme immune 449:454 arg1 deficiency 456:465 immune deficiency 449:465 immune deficiency 449:465 The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. 35637269 7 65 theme compound 731:738 arg1 variants 753:760 compound heterozygous variants 731:760 compound heterozygous variants in MAN2B2 731:770 In this study, we described the clinical presentations of a CDG proband with compound heterozygous variants in MAN2B2. 35637269 0 66 theme Chinese 57:63 arg1 child 65:69 a Chinese child 55:69 a Chinese child with congenital disorders of glycosylation 55:112 Compound heterozygous variants in MAN2B2 identified in a Chinese child with congenital disorders of glycosylation. 35637269 2 67 theme significant 243:253 arg1 morbidity 255:263 significant morbidity 243:263 significant morbidity 243:263 It is characterized by multi-organ dysfunction with significant morbidity and mortality. 35637269 5 68 theme developmental 521:533 arg1 delay 535:539 severe developmental delay 514:539 severe developmental delay 514:539 The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. 35637269 6 69 theme variation 602:610 arg1 pathogenesis 579:590 the pathogenesis 575:590 the pathogenesis of MAN2B2 variation 575:610 More cases are needed to support the pathogenesis of MAN2B2 variation and elucidate its clinical heterogeneity. 35637269 6 70 theme clinical 630:637 arg1 heterogeneity 639:651 its clinical heterogeneity 626:651 its clinical heterogeneity 626:651 More cases are needed to support the pathogenesis of MAN2B2 variation and elucidate its clinical heterogeneity. 35637269 7 71 theme heterozygous 740:751 arg1 variants 753:760 compound heterozygous variants 731:760 compound heterozygous variants in MAN2B2 731:770 In this study, we described the clinical presentations of a CDG proband with compound heterozygous variants in MAN2B2. 35470373 4 0 theme CSL040 817:822 arg1 preparations 824:835 recombinant CSL040 preparations 805:835 recombinant CSL040 preparations with varying asialo-N-glycan levels 805:871 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 4 1 theme asialo-N-glycan 850:864 arg1 levels 866:871 varying asialo-N-glycan levels 842:871 varying asialo-N-glycan levels 842:871 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 5 2 with clearance 957:965 arg1 proportion 989:998 a high proportion 982:998 a high proportion of asialo-N-glycans 982:1018 The clearance mechanism likely involves the asialoglycoprotein receptor (ASGR), as clearance of CSL040 with a high proportion of asialo-N-glycans was attenuated in vivo by co-administration of rats with asialofetuin, which saturates the ASGR. 35470373 9 3 theme sialylation 1648:1658 arg1 optimization 1660:1671 sialylation optimization 1648:1671 sialylation optimization 1648:1671 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 9 3 theme sialylation 1648:1658 arg1 consideration 1689:1701 an important consideration 1676:1701 an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1 1676:1885 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 7 4 theme lectin 1407:1412 arg1 pathways 1414:1421 the classical and lectin pathways 1389:1421 pathways 1414:1421 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 1 5 theme membrane-bound 173:186 arg1 regulator 188:196 a potent membrane-bound regulator 164:196 a potent membrane-bound regulator of complement 164:210 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 5 theme membrane-bound 173:186 arg1 Receptor 142:149 Human Complement Receptor 1 125:151 Human Complement Receptor 1 (HuCR1) 125:159 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 7 6 theme classical 1393:1401 arg1 pathways 1414:1421 the classical and lectin pathways 1389:1421 pathways 1414:1421 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 4 7 theme varying 842:848 arg1 levels 866:871 varying asialo-N-glycan levels 842:871 varying asialo-N-glycan levels 842:871 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 2 8 theme Soluble 292:298 arg1 versions 300:307 Soluble versions 292:307 Soluble versions of HuCR1 292:316 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 9 9 theme important 1679:1687 arg1 optimization 1660:1671 sialylation optimization 1648:1671 sialylation optimization 1648:1671 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 9 9 theme important 1679:1687 arg1 consideration 1689:1701 an important consideration 1676:1701 an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1 1676:1885 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 6 10 theme systemic 1196:1203 arg1 administration 1205:1218 systemic administration 1196:1218 systemic administration 1196:1218 Biodistribution studies also showed CSL040 localization to the liver following systemic administration. 35470373 3 11 dep pharmacokinetic 575:589 arg1 PK 592:593 PK 592:593 PK 592:593 However, the role of N-linked glycosylation in determining its pharmacokinetic (PK) and pharmacodynamic (PD) properties is only partly understood. 35470373 7 12 theme pathway 1367:1373 arg1 inhibition 1315:1324 extended inhibition 1306:1324 extended inhibition in both rats and NHPs of the alternative pathway 1306:1373 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 9 13 contain has 1818:1820 arg2 responses 1837:1845 superior PK/PD responses 1822:1845 superior PK/PD responses 1822:1845 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 9 13 contain has 1818:1820 arg1 CSL040 1811:1816 CSL040 1811:1816 CSL040 1811:1816 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 9 14 theme HuCR1-based 1718:1728 arg1 candidates 1742:1751 HuCR1-based therapeutic candidates 1718:1751 HuCR1-based therapeutic candidates such as CSL040 with improved PK properties 1718:1794 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 9 14 theme HuCR1-based 1718:1728 arg1 CSL040 1761:1766 CSL040 1761:1766 CSL040 with improved PK properties 1761:1794 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 3 15 theme glycosylation 542:554 arg1 role 525:528 the role 521:528 the role of N-linked glycosylation in determining its pharmacokinetic (PK) and pharmacodynamic (PD) properties 521:630 However, the role of N-linked glycosylation in determining its pharmacokinetic (PK) and pharmacodynamic (PD) properties is only partly understood. 35470373 5 16 theme clearance 878:886 arg1 mechanism 888:896 The clearance mechanism 874:896 The clearance mechanism 874:896 The clearance mechanism likely involves the asialoglycoprotein receptor (ASGR), as clearance of CSL040 with a high proportion of asialo-N-glycans was attenuated in vivo by co-administration of rats with asialofetuin, which saturates the ASGR. 35470373 4 17 from rats 763:766 arg1 levels 718:723 the asialo-N-glycan levels 698:723 the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs) 698:796 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 2 18 theme homologous 476:485 arg1 domain 494:499 the C-terminal long homologous repeat domain 456:499 the C-terminal long homologous repeat domain D (LHR-D) 456:509 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 5 19 with rats 1067:1070 arg1 asialofetuin 1077:1088 asialofetuin 1077:1088 asialofetuin 1077:1088 The clearance mechanism likely involves the asialoglycoprotein receptor (ASGR), as clearance of CSL040 with a high proportion of asialo-N-glycans was attenuated in vivo by co-administration of rats with asialofetuin, which saturates the ASGR. 35470373 9 20 with CSL040 1761:1766 arg1 properties 1785:1794 improved PK properties 1773:1794 improved PK properties 1773:1794 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 4 21 from properties 749:758 arg1 NHPs 792:795 NHPs 792:795 NHPs 792:795 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 4 21 from properties 749:758 arg1 rats 763:766 rats 763:766 rats 763:766 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 4 21 from properties 749:758 arg1 primates 782:789 non-human primates 772:789 non-human primates (NHPs) 772:796 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 2 22 theme C-terminal 460:469 arg1 domain 494:499 the C-terminal long homologous repeat domain 456:499 the C-terminal long homologous repeat domain D (LHR-D) 456:509 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 0 23 theme CR1 103:105 arg1 activity 107:114 CR1 activity 103:114 CR1 activity 103:114 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 9 24 theme PK 1782:1783 arg1 properties 1785:1794 improved PK properties 1773:1794 improved PK properties 1773:1794 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 1 25 dep ligands 271:277 arg1 C3b 279:281 C3b 279:281 C3b 279:281 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 25 dep ligands 271:277 arg1 ligands 271:277 its ligands 267:277 its ligands C3b and C4b 267:289 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 25 dep ligands 271:277 arg1 C4b 287:289 C4b 287:289 C4b 287:289 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 4 26 theme CSL040 728:733 arg1 levels 718:723 the asialo-N-glycan levels 698:723 the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs) 698:796 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 4 27 from CSL040 728:733 arg1 NHPs 792:795 NHPs 792:795 NHPs 792:795 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 4 27 from CSL040 728:733 arg1 rats 763:766 rats 763:766 rats 763:766 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 4 27 from CSL040 728:733 arg1 primates 782:789 non-human primates 772:789 non-human primates (NHPs) 772:796 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 2 28 theme full-length 368:378 arg1 domain 394:399 the recombinant full-length extracellular domain 352:399 the recombinant full-length extracellular domain 352:399 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 9 29 theme PK/PD 1831:1835 arg1 responses 1837:1845 superior PK/PD responses 1822:1845 superior PK/PD responses 1822:1845 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 4 30 from levels 718:723 arg1 NHPs 792:795 NHPs 792:795 NHPs 792:795 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 4 30 from levels 718:723 arg1 rats 763:766 rats 763:766 rats 763:766 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 4 30 from levels 718:723 arg1 primates 782:789 non-human primates 772:789 non-human primates (NHPs) 772:796 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 0 31 theme Sialylation-dependent 0:20 arg1 hallmarks 90:98 hallmarks 90:98 hallmarks of CR1 activity 90:114 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 0 31 theme Sialylation-dependent 0:20 arg1 inhibition 75:84 differential complement pathway inhibition 43:84 differential complement pathway inhibition 43:84 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 0 31 theme Sialylation-dependent 0:20 arg1 pharmacokinetics 22:37 Sialylation-dependent pharmacokinetics 0:37 Sialylation-dependent pharmacokinetics 0:37 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 7 32 dep uncovered 1233:1241 arg1 with 1301:1304 with 1301:1304 with 1301:1304 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 1 33 theme Human 125:129 arg1 regulator 188:196 a potent membrane-bound regulator 164:196 a potent membrane-bound regulator of complement 164:210 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 33 theme Human 125:129 arg1 Receptor 142:149 Human Complement Receptor 1 125:151 Human Complement Receptor 1 (HuCR1) 125:159 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 33 theme Human 125:129 arg1 HuCR1 154:158 HuCR1 154:158 HuCR1 154:158 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 3 34 link N-linked 533:540 arg1 glycosylation 542:554 N-linked glycosylation 533:554 N-linked glycosylation 533:554 However, the role of N-linked glycosylation in determining its pharmacokinetic (PK) and pharmacodynamic (PD) properties is only partly understood. 35470373 4 35 theme non-human 772:780 arg1 NHPs 792:795 NHPs 792:795 NHPs 792:795 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 4 35 theme non-human 772:780 arg1 primates 782:789 non-human primates 772:789 non-human primates (NHPs) 772:796 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 0 36 theme complement 56:65 arg1 hallmarks 90:98 hallmarks 90:98 hallmarks of CR1 activity 90:114 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 0 36 theme complement 56:65 arg1 inhibition 75:84 differential complement pathway inhibition 43:84 differential complement pathway inhibition 43:84 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 0 36 theme complement 56:65 arg1 pharmacokinetics 22:37 Sialylation-dependent pharmacokinetics 0:37 Sialylation-dependent pharmacokinetics 0:37 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 1 37 with interaction 250:260 arg1 C3b 279:281 C3b 279:281 C3b 279:281 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 37 with interaction 250:260 arg1 ligands 271:277 its ligands 267:277 its ligands C3b and C4b 267:289 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 37 with interaction 250:260 arg1 C4b 287:289 C4b 287:289 C4b 287:289 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 2 38 theme truncated 430:438 arg1 CSL040 420:425 CSL040 420:425 CSL040 420:425 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 2 38 theme truncated 430:438 arg1 version 440:446 a truncated version 428:446 a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D) 428:509 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 9 39 theme full-length 1861:1871 arg1 HuCR1 1881:1885 full-length soluble HuCR1 1861:1885 full-length soluble HuCR1 1861:1885 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 3 40 theme pharmacokinetic 575:589 arg1 properties 621:630 its pharmacokinetic (PK) and pharmacodynamic (PD) properties 571:630 its pharmacokinetic (PK) and pharmacodynamic (PD) properties 571:630 However, the role of N-linked glycosylation in determining its pharmacokinetic (PK) and pharmacodynamic (PD) properties is only partly understood. 35470373 4 41 theme properties 749:758 arg1 levels 718:723 the asialo-N-glycan levels 698:723 the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs) 698:796 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 2 42 theme HuCR1 312:316 arg1 versions 300:307 Soluble versions 292:307 Soluble versions of HuCR1 292:316 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 8 43 theme extracellular 1578:1590 arg1 HuCR1 1602:1606 HuCR1 1602:1606 HuCR1 1602:1606 Further studies showed that this effect was dose dependent and observed with both CSL040 and the full-length extracellular domain of HuCR1. 35470373 8 43 theme extracellular 1578:1590 arg1 domain 1592:1597 the full-length extracellular domain 1562:1597 the full-length extracellular domain of HuCR1 1562:1606 Further studies showed that this effect was dose dependent and observed with both CSL040 and the full-length extracellular domain of HuCR1. 35470373 2 44 theme extracellular 380:392 arg1 domain 394:399 the recombinant full-length extracellular domain 352:399 the recombinant full-length extracellular domain 352:399 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 3 45 dep pharmacodynamic 600:614 arg1 PD 617:618 PD 617:618 PD 617:618 However, the role of N-linked glycosylation in determining its pharmacokinetic (PK) and pharmacodynamic (PD) properties is only partly understood. 35470373 5 46 theme CSL040 970:975 arg1 clearance 957:965 clearance 957:965 clearance of CSL040 with a high proportion of asialo-N-glycans 957:1018 The clearance mechanism likely involves the asialoglycoprotein receptor (ASGR), as clearance of CSL040 with a high proportion of asialo-N-glycans was attenuated in vivo by co-administration of rats with asialofetuin, which saturates the ASGR. 35470373 7 47 theme PD 1256:1257 arg1 effects 1259:1265 differential PD effects 1243:1265 differential PD effects by CSL040 on complement pathways 1243:1298 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 7 48 theme PK 1457:1458 arg1 profile 1460:1466 its PK profile 1453:1466 its PK profile 1453:1466 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 4 49 theme recombinant 805:815 arg1 preparations 824:835 recombinant CSL040 preparations 805:835 recombinant CSL040 preparations with varying asialo-N-glycan levels 805:871 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 6 50 theme CSL040 1153:1158 arg1 localization 1160:1171 CSL040 localization 1153:1171 CSL040 localization 1153:1171 Biodistribution studies also showed CSL040 localization to the liver following systemic administration. 35470373 1 51 theme potent 166:171 arg1 regulator 188:196 a potent membrane-bound regulator 164:196 a potent membrane-bound regulator of complement 164:210 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 51 theme potent 166:171 arg1 Receptor 142:149 Human Complement Receptor 1 125:151 Human Complement Receptor 1 (HuCR1) 125:159 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 7 52 from effects 1259:1265 arg1 pathways 1291:1298 complement pathways 1280:1298 complement pathways 1280:1298 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 6 53 theme Biodistribution 1117:1131 arg1 studies 1133:1139 Biodistribution studies 1117:1139 Biodistribution studies 1117:1139 Biodistribution studies also showed CSL040 localization to the liver following systemic administration. 35470373 1 54 theme complement 201:210 arg1 regulator 188:196 a potent membrane-bound regulator 164:196 a potent membrane-bound regulator of complement 164:210 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 54 theme complement 201:210 arg1 Receptor 142:149 Human Complement Receptor 1 125:151 Human Complement Receptor 1 (HuCR1) 125:159 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 3 55 theme N-linked 533:540 arg1 glycosylation 542:554 N-linked glycosylation 533:554 N-linked glycosylation 533:554 However, the role of N-linked glycosylation in determining its pharmacokinetic (PK) and pharmacodynamic (PD) properties is only partly understood. 35470373 4 56 from primates 782:789 arg1 levels 718:723 the asialo-N-glycan levels 698:723 the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs) 698:796 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 1 57 theme Complement 131:140 arg1 regulator 188:196 a potent membrane-bound regulator 164:196 a potent membrane-bound regulator of complement 164:210 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 57 theme Complement 131:140 arg1 Receptor 142:149 Human Complement Receptor 1 125:151 Human Complement Receptor 1 (HuCR1) 125:159 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 1 57 theme Complement 131:140 arg1 HuCR1 154:158 HuCR1 154:158 HuCR1 154:158 Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. 35470373 9 58 theme therapeutic 1730:1740 arg1 candidates 1742:1751 HuCR1-based therapeutic candidates 1718:1751 HuCR1-based therapeutic candidates such as CSL040 with improved PK properties 1718:1794 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 9 58 theme therapeutic 1730:1740 arg1 CSL040 1761:1766 CSL040 1761:1766 CSL040 with improved PK properties 1761:1794 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 7 59 theme alternative 1355:1365 arg1 pathway 1367:1373 the alternative pathway 1351:1373 the alternative pathway 1351:1373 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 5 60 theme asialo-N-glycans 1003:1018 arg1 proportion 989:998 a high proportion 982:998 a high proportion of asialo-N-glycans 982:1018 The clearance mechanism likely involves the asialoglycoprotein receptor (ASGR), as clearance of CSL040 with a high proportion of asialo-N-glycans was attenuated in vivo by co-administration of rats with asialofetuin, which saturates the ASGR. 35470373 4 61 with preparations 824:835 arg1 levels 866:871 varying asialo-N-glycan levels 842:871 varying asialo-N-glycan levels 842:871 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 8 62 theme Further 1469:1475 arg1 studies 1477:1483 Further studies 1469:1483 Further studies 1469:1483 Further studies showed that this effect was dose dependent and observed with both CSL040 and the full-length extracellular domain of HuCR1. 35470373 2 63 theme long 471:474 arg1 domain 494:499 the C-terminal long homologous repeat domain 456:499 the C-terminal long homologous repeat domain D (LHR-D) 456:509 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 0 64 theme activity 107:114 arg1 hallmarks 90:98 hallmarks 90:98 hallmarks of CR1 activity 90:114 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 0 64 theme activity 107:114 arg1 inhibition 75:84 differential complement pathway inhibition 43:84 differential complement pathway inhibition 43:84 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 0 64 theme activity 107:114 arg1 pharmacokinetics 22:37 Sialylation-dependent pharmacokinetics 0:37 Sialylation-dependent pharmacokinetics 0:37 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 9 65 theme improved 1773:1780 arg1 properties 1785:1794 improved PK properties 1773:1794 improved PK properties 1773:1794 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 5 66 theme rats 1067:1070 arg1 co-administration 1046:1062 co-administration 1046:1062 co-administration of rats with asialofetuin, which saturates the ASGR 1046:1114 The clearance mechanism likely involves the asialoglycoprotein receptor (ASGR), as clearance of CSL040 with a high proportion of asialo-N-glycans was attenuated in vivo by co-administration of rats with asialofetuin, which saturates the ASGR. 35470373 5 67 gly asialoglycoprotein 918:935 arg1 asialoglycoprotein 918:935 the asialoglycoprotein receptor 914:944 the asialoglycoprotein receptor (ASGR) 914:951 The clearance mechanism likely involves the asialoglycoprotein receptor (ASGR), as clearance of CSL040 with a high proportion of asialo-N-glycans was attenuated in vivo by co-administration of rats with asialofetuin, which saturates the ASGR. 35470373 2 68 theme recombinant 356:366 arg1 domain 394:399 the recombinant full-length extracellular domain 352:399 the recombinant full-length extracellular domain 352:399 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 7 69 theme extended 1306:1313 arg1 inhibition 1315:1324 extended inhibition 1306:1324 extended inhibition in both rats and NHPs of the alternative pathway 1306:1373 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 0 70 theme differential 43:54 arg1 hallmarks 90:98 hallmarks 90:98 hallmarks of CR1 activity 90:114 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 0 70 theme differential 43:54 arg1 inhibition 75:84 differential complement pathway inhibition 43:84 differential complement pathway inhibition 43:84 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 0 70 theme differential 43:54 arg1 pharmacokinetics 22:37 Sialylation-dependent pharmacokinetics 0:37 Sialylation-dependent pharmacokinetics 0:37 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 2 71 dep domain 494:499 arg1 LHR-D 504:508 LHR-D 504:508 LHR-D 504:508 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 2 71 dep domain 494:499 arg1 D 501:501 D 501:501 the C-terminal long homologous repeat domain D (LHR-D) 456:509 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 5 72 theme asialoglycoprotein 918:935 arg1 ASGR 947:950 ASGR 947:950 ASGR 947:950 The clearance mechanism likely involves the asialoglycoprotein receptor (ASGR), as clearance of CSL040 with a high proportion of asialo-N-glycans was attenuated in vivo by co-administration of rats with asialofetuin, which saturates the ASGR. 35470373 5 72 theme asialoglycoprotein 918:935 arg1 receptor 937:944 the asialoglycoprotein receptor 914:944 the asialoglycoprotein receptor (ASGR) 914:951 The clearance mechanism likely involves the asialoglycoprotein receptor (ASGR), as clearance of CSL040 with a high proportion of asialo-N-glycans was attenuated in vivo by co-administration of rats with asialofetuin, which saturates the ASGR. 35470373 9 73 theme superior 1822:1829 arg1 responses 1837:1845 superior PK/PD responses 1822:1845 superior PK/PD responses 1822:1845 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 3 74 theme pharmacodynamic 600:614 arg1 properties 621:630 its pharmacokinetic (PK) and pharmacodynamic (PD) properties 571:630 its pharmacokinetic (PK) and pharmacodynamic (PD) properties 571:630 However, the role of N-linked glycosylation in determining its pharmacokinetic (PK) and pharmacodynamic (PD) properties is only partly understood. 35470373 4 75 theme asialo-N-glycan 702:716 arg1 levels 718:723 the asialo-N-glycan levels 698:723 the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs) 698:796 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 0 76 theme pathway 67:73 arg1 hallmarks 90:98 hallmarks 90:98 hallmarks of CR1 activity 90:114 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 0 76 theme pathway 67:73 arg1 inhibition 75:84 differential complement pathway inhibition 43:84 differential complement pathway inhibition 43:84 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 0 76 theme pathway 67:73 arg1 pharmacokinetics 22:37 Sialylation-dependent pharmacokinetics 0:37 Sialylation-dependent pharmacokinetics 0:37 Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. 35470373 7 77 theme complement 1280:1289 arg1 pathways 1291:1298 complement pathways 1280:1298 complement pathways 1280:1298 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 2 78 theme repeat 487:492 arg1 domain 494:499 the C-terminal long homologous repeat domain 456:499 the C-terminal long homologous repeat domain D (LHR-D) 456:509 Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). 35470373 5 79 theme high 984:987 arg1 proportion 989:998 a high proportion 982:998 a high proportion of asialo-N-glycans 982:1018 The clearance mechanism likely involves the asialoglycoprotein receptor (ASGR), as clearance of CSL040 with a high proportion of asialo-N-glycans was attenuated in vivo by co-administration of rats with asialofetuin, which saturates the ASGR. 35470373 8 80 theme full-length 1566:1576 arg1 HuCR1 1602:1606 HuCR1 1602:1606 HuCR1 1602:1606 Further studies showed that this effect was dose dependent and observed with both CSL040 and the full-length extracellular domain of HuCR1. 35470373 8 80 theme full-length 1566:1576 arg1 domain 1592:1597 the full-length extracellular domain 1562:1597 the full-length extracellular domain of HuCR1 1562:1606 Further studies showed that this effect was dose dependent and observed with both CSL040 and the full-length extracellular domain of HuCR1. 35470373 9 81 theme soluble 1873:1879 arg1 HuCR1 1881:1885 full-length soluble HuCR1 1861:1885 full-length soluble HuCR1 1861:1885 Taken together, our data suggests that sialylation optimization is an important consideration for developing HuCR1-based therapeutic candidates such as CSL040 with improved PK properties and shows that CSL040 has superior PK/PD responses compared with full-length soluble HuCR1. 35470373 4 82 theme PK/PD 743:747 arg1 properties 749:758 its PK/PD properties 739:758 its PK/PD properties 739:758 We demonstrated a relationship between the asialo-N-glycan levels of CSL040 and its PK/PD properties in rats and non-human primates (NHPs), using recombinant CSL040 preparations with varying asialo-N-glycan levels. 35470373 7 83 from inhibition 1315:1324 arg1 NHPs 1343:1346 NHPs 1343:1346 NHPs 1343:1346 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 7 83 from inhibition 1315:1324 arg1 rats 1334:1337 rats 1334:1337 rats 1334:1337 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 7 84 theme differential 1243:1254 arg1 effects 1259:1265 differential PD effects 1243:1265 differential PD effects by CSL040 on complement pathways 1243:1298 Our studies uncovered differential PD effects by CSL040 on complement pathways, with extended inhibition in both rats and NHPs of the alternative pathway compared with the classical and lectin pathways that were not correlated with its PK profile. 35470373 8 85 theme HuCR1 1602:1606 arg1 HuCR1 1602:1606 HuCR1 1602:1606 HuCR1 1602:1606 Further studies showed that this effect was dose dependent and observed with both CSL040 and the full-length extracellular domain of HuCR1. 35470373 8 85 theme HuCR1 1602:1606 arg1 domain 1592:1597 the full-length extracellular domain 1562:1597 the full-length extracellular domain of HuCR1 1562:1606 Further studies showed that this effect was dose dependent and observed with both CSL040 and the full-length extracellular domain of HuCR1. 35470373 8 85 theme HuCR1 1602:1606 arg1 CSL040 1551:1556 CSL040 1551:1556 CSL040 1551:1556 Further studies showed that this effect was dose dependent and observed with both CSL040 and the full-length extracellular domain of HuCR1. 35149460 0 0 theme N-glycans 79:87 arg1 synthesis 45:53 the synthesis 41:53 the synthesis of Bi- and triantennary N-glycans 41:87 Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans and exploring their activities against siglecs. 35149460 1 1 dep amount 307:312 arg1 2 300:300 2 300:300 2 300:300 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 8 2 theme 2,6 1390:1392 arg1 2,3 1396:1398 2,3 1396:1398 2,3 1396:1398 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 8 2 theme 2,6 1390:1392 arg1 α 1394:1394 α(2,6)α 1388:1394 α(2,6)α(2,3) 1388:1399 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 4 3 theme glycans 813:819 arg1 library 783:789 The synthesized small library 761:789 The synthesized small library of mannose core-based glycans and linear O-glycans 761:840 The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. 35149460 3 4 theme mannose 694:700 arg1 structures 707:716 mannose core structures 694:716 mannose core structures 694:716 In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides. 35149460 0 5 theme triantennary 66:77 arg1 N-glycans 79:87 Bi- and triantennary N-glycans 58:87 Bi- and triantennary N-glycans 58:87 Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans and exploring their activities against siglecs. 35149460 1 6 theme transferases 317:328 arg1 inhibition 366:375 byproduct feedback inhibition 347:375 3) byproduct feedback inhibition 344:375 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 6 theme transferases 317:328 arg1 transferases 317:328 transferases 317:328 transferases required 317:337 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 6 theme transferases 317:328 arg1 amount 307:312 the amount 303:312 2) the amount of transferases required 300:337 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 6 theme transferases 317:328 arg1 nucleotides 287:297 exorbitant sugar nucleotides 270:297 exorbitant sugar nucleotides 270:297 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 6 theme transferases 317:328 arg1 consumption 255:265 the consumption 251:265 1) the consumption of exorbitant sugar nucleotides 248:297 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 8 7 theme high-affinity 1576:1588 arg1 ligands 1590:1596 high-affinity ligands 1576:1596 high-affinity ligands 1576:1596 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 2 8 from branches 530:537 arg1 manner 552:557 a uniform manner 542:557 a uniform manner 542:557 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 2 9 with SNRS 488:491 arg1 purities 514:521 purities 514:521 purities 514:521 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 2 9 with SNRS 488:491 arg1 yields 503:508 high yields 498:508 high yields 498:508 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 8 10 theme α 1388:1388 arg1 2,3 1396:1398 2,3 1396:1398 2,3 1396:1398 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 8 10 theme α 1388:1388 arg1 α 1394:1394 α(2,6)α 1388:1394 α(2,6)α(2,3) 1388:1399 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 8 11 theme further 1553:1559 arg1 development 1561:1571 the further development 1549:1571 the further development of high-affinity ligands 1549:1596 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 8 12 theme -branched 1425:1433 arg1 glycans 1435:1441 linear and α(2,3)α(2,6)-branched glycans 1402:1441 linear and α(2,3)α(2,6)-branched glycans 1402:1441 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 2 13 theme high 498:501 arg1 yields 503:508 high yields 498:508 high yields 498:508 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 3 14 theme acceptor 650:657 arg1 substrates 721:730 substrates 721:730 substrates for target oligosaccharides 721:758 In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides. 35149460 3 14 theme acceptor 650:657 arg1 tolerance 659:667 a wide acceptor tolerance 643:667 a wide acceptor tolerance for bi- and triantennary mannose core structures 643:716 In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides. 35149460 4 15 theme binding 866:872 arg1 affinity 874:881 their binding affinity 860:881 their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 860:935 The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. 35149460 3 16 theme core 702:705 arg1 structures 707:716 mannose core structures 694:716 mannose core structures 694:716 In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides. 35149460 4 17 theme O-glycans 832:840 arg1 library 783:789 The synthesized small library 761:789 The synthesized small library of mannose core-based glycans and linear O-glycans 761:840 The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. 35149460 8 18 theme ligands 1590:1596 arg1 development 1561:1571 the further development 1549:1571 the further development of high-affinity ligands 1549:1596 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 6 19 theme tri 1128:1130 arg1 antennary 1132:1140 tri antennary 1128:1140 tri antennary 1128:1140 An increase in branching from mono to di or tri antennary did not necessarily lead to increasing affinity. 35149460 7 20 theme /α 1241:1242 arg1 2,8 1250:1252 2,8 1250:1252 2,8 1250:1252 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 20 theme /α 1241:1242 arg1 α 1248:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α 1204:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) 1204:1253 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 21 theme 2,6 1244:1246 arg1 2,8 1250:1252 2,8 1250:1252 2,8 1250:1252 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 21 theme 2,6 1244:1246 arg1 α 1248:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α 1204:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) 1204:1253 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 4 22 theme linear 825:830 arg1 O-glycans 832:840 linear O-glycans 825:840 linear O-glycans 825:840 The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. 35149460 4 23 theme binding 970:976 arg1 preferences 978:988 their structure-based binding preferences 948:988 their structure-based binding preferences 948:988 The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. 35149460 8 24 theme α 1394:1394 arg1 recognition 1373:1383 Explicit recognition 1364:1383 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15 1364:1465 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 0 25 theme nucleotide 6:15 arg1 system 30:35 Sugar nucleotide regeneration system 0:35 Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans 0:87 Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans and exploring their activities against siglecs. 35149460 3 26 dep bi- 673:675 arg1 structures 707:716 mannose core structures 694:716 mannose core structures 694:716 In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides. 35149460 2 27 link N-linked 432:439 arg1 core 449:452 the N-linked mannose core 428:452 the N-linked mannose core 428:452 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 5 28 theme overlapping 1057:1067 arg1 specificities 1069:1081 few distinct yet overlapping specificities 1040:1081 few distinct yet overlapping specificities 1040:1081 Microarray data revealed that each Siglec showed few distinct yet overlapping specificities. 35149460 1 29 theme sugar 182:186 arg1 system 212:217 the sugar nucleotide regeneration system 178:217 the sugar nucleotide regeneration system (SNRS) protocol 178:233 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 29 theme sugar 182:186 arg1 SNRS 220:223 SNRS 220:223 SNRS 220:223 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 0 30 theme Sugar 0:4 arg1 system 30:35 Sugar nucleotide regeneration system 0:35 Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans 0:87 Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans and exploring their activities against siglecs. 35149460 4 31 theme structure-based 954:968 arg1 preferences 978:988 their structure-based binding preferences 948:988 their structure-based binding preferences 948:988 The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. 35149460 1 32 theme nucleotide 188:197 arg1 system 212:217 the sugar nucleotide regeneration system 178:217 the sugar nucleotide regeneration system (SNRS) protocol 178:233 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 32 theme nucleotide 188:197 arg1 SNRS 220:223 SNRS 220:223 SNRS 220:223 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 33 theme exorbitant 270:279 arg1 nucleotides 287:297 exorbitant sugar nucleotides 270:297 exorbitant sugar nucleotides 270:297 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 3 34 theme bacterial 604:612 arg1 glycosyltransferases 614:633 bacterial glycosyltransferases 604:633 bacterial glycosyltransferases 604:633 In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides. 35149460 1 35 theme regeneration 199:210 arg1 system 212:217 the sugar nucleotide regeneration system 178:217 the sugar nucleotide regeneration system (SNRS) protocol 178:233 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 35 theme regeneration 199:210 arg1 SNRS 220:223 SNRS 220:223 SNRS 220:223 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 2 36 theme LacNAc 393:398 arg1 extensions/modifications 400:423 LacNAc extensions/modifications 393:423 LacNAc extensions/modifications of the N-linked mannose core 393:452 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 1 37 theme sugar 281:285 arg1 nucleotides 287:297 exorbitant sugar nucleotides 270:297 exorbitant sugar nucleotides 270:297 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 38 theme byproduct 347:355 arg1 inhibition 366:375 byproduct feedback inhibition 347:375 3) byproduct feedback inhibition 344:375 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 39 theme system 212:217 arg1 protocol 226:233 the sugar nucleotide regeneration system (SNRS) protocol 178:233 the sugar nucleotide regeneration system (SNRS) protocol 178:233 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 40 theme nucleotides 287:297 arg1 inhibition 366:375 byproduct feedback inhibition 347:375 3) byproduct feedback inhibition 344:375 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 40 theme nucleotides 287:297 arg1 transferases 317:328 transferases 317:328 transferases required 317:337 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 40 theme nucleotides 287:297 arg1 amount 307:312 the amount 303:312 2) the amount of transferases required 300:337 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 40 theme nucleotides 287:297 arg1 nucleotides 287:297 exorbitant sugar nucleotides 270:297 exorbitant sugar nucleotides 270:297 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 40 theme nucleotides 287:297 arg1 consumption 255:265 the consumption 251:265 1) the consumption of exorbitant sugar nucleotides 248:297 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 1 41 theme feedback 357:364 arg1 inhibition 366:375 byproduct feedback inhibition 347:375 3) byproduct feedback inhibition 344:375 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 4 42 theme core-based 802:811 arg1 glycans 813:819 mannose core-based glycans 794:819 mannose core-based glycans 794:819 The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. 35149460 7 43 theme α 1235:1235 arg1 2,8 1250:1252 2,8 1250:1252 2,8 1250:1252 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 43 theme α 1235:1235 arg1 α 1248:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α 1204:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) 1204:1253 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 2 44 theme core 449:452 arg1 extensions/modifications 400:423 LacNAc extensions/modifications 393:423 LacNAc extensions/modifications of the N-linked mannose core 393:452 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 7 45 theme strong 1334:1339 arg1 affinity 1341:1348 a strong affinity 1332:1348 a strong affinity for Siglec-9 1332:1361 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 5 46 theme few 1040:1042 arg1 specificities 1069:1081 few distinct yet overlapping specificities 1040:1081 few distinct yet overlapping specificities 1040:1081 Microarray data revealed that each Siglec showed few distinct yet overlapping specificities. 35149460 4 47 theme mannose 794:800 arg1 glycans 813:819 mannose core-based glycans 794:819 mannose core-based glycans 794:819 The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. 35149460 7 48 theme high 1262:1265 arg1 specificity 1267:1277 high specificity 1262:1277 high specificity 1262:1277 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 2 49 theme mannose 441:447 arg1 core 449:452 the N-linked mannose core 428:452 the N-linked mannose core 428:452 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 8 50 theme linear 1402:1407 arg1 glycans 1435:1441 linear and α(2,3)α(2,6)-branched glycans 1402:1441 linear and α(2,3)α(2,6)-branched glycans 1402:1441 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 2 51 theme uniform 544:550 arg1 manner 552:557 a uniform manner 542:557 a uniform manner 542:557 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 5 52 theme distinct 1044:1051 arg1 specificities 1069:1081 few distinct yet overlapping specificities 1040:1081 few distinct yet overlapping specificities 1040:1081 Microarray data revealed that each Siglec showed few distinct yet overlapping specificities. 35149460 7 53 theme 2,3 1231:1233 arg1 2,8 1250:1252 2,8 1250:1252 2,8 1250:1252 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 53 theme 2,3 1231:1233 arg1 α 1248:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α 1204:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) 1204:1253 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 2 54 theme N-linked 432:439 arg1 core 449:452 the N-linked mannose core 428:452 the N-linked mannose core 428:452 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 3 55 theme target 736:741 arg1 oligosaccharides 743:758 target oligosaccharides 736:758 target oligosaccharides 736:758 In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides. 35149460 2 56 dep carried 459:465 arg1 out 467:469 out 467:469 out 467:469 In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. 35149460 5 57 theme Microarray 991:1000 arg1 data 1002:1005 Microarray data 991:1005 Microarray data 991:1005 Microarray data revealed that each Siglec showed few distinct yet overlapping specificities. 35149460 3 58 theme wide 645:648 arg1 substrates 721:730 substrates 721:730 substrates for target oligosaccharides 721:758 In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides. 35149460 3 58 theme wide 645:648 arg1 tolerance 659:667 a wide acceptor tolerance 643:667 a wide acceptor tolerance for bi- and triantennary mannose core structures 643:716 In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides. 35149460 6 59 theme increasing 1170:1179 arg1 affinity 1181:1188 increasing affinity 1170:1188 increasing affinity 1170:1188 An increase in branching from mono to di or tri antennary did not necessarily lead to increasing affinity. 35149460 7 60 with Glycans 1191:1197 arg1 2,8 1250:1252 2,8 1250:1252 2,8 1250:1252 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 60 with Glycans 1191:1197 arg1 α 1248:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α 1204:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) 1204:1253 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 1 61 dep consumption 255:265 arg1 1 248:248 1 248:248 1 248:248 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 4 62 theme small 777:781 arg1 library 783:789 The synthesized small library 761:789 The synthesized small library of mannose core-based glycans and linear O-glycans 761:840 The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. 35149460 8 63 theme potential 1524:1532 arg1 candidates 1534:1543 potential candidates 1524:1543 potential candidates for the further development of high-affinity ligands 1524:1596 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 8 63 theme potential 1524:1532 arg1 structures 1502:1511 these structures 1496:1511 these structures 1496:1511 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 7 64 theme α 1229:1229 arg1 2,8 1250:1252 2,8 1250:1252 2,8 1250:1252 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 64 theme α 1229:1229 arg1 α 1248:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α 1204:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) 1204:1253 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 8 65 theme glycans 1435:1441 arg1 recognition 1373:1383 Explicit recognition 1364:1383 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15 1364:1465 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 1 66 dep inhibition 366:375 arg1 3 344:344 3 344:344 3 344:344 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 7 67 theme sLex 1310:1313 arg1 2,3 1317:1319 2,3 1317:1319 2,3 1317:1319 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 67 theme sLex 1310:1313 arg1 α 1315:1315 sLex α 1310:1315 sLex α(2,3) 1310:1320 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 4 68 theme synthesized 765:775 arg1 library 783:789 The synthesized small library 761:789 The synthesized small library of mannose core-based glycans and linear O-glycans 761:840 The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. 35149460 1 69 theme Enzymatic 137:145 arg1 synthesis 147:155 Enzymatic synthesis 137:155 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol 137:233 Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. 35149460 7 70 theme 2,8 1237:1239 arg1 2,8 1250:1252 2,8 1250:1252 2,8 1250:1252 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 70 theme 2,8 1237:1239 arg1 α 1248:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α 1204:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) 1204:1253 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 71 theme disialoside 1208:1218 arg1 2,8 1250:1252 2,8 1250:1252 2,8 1250:1252 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 71 theme disialoside 1208:1218 arg1 α 1248:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α 1204:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) 1204:1253 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 0 72 theme Bi- 58:60 arg1 N-glycans 79:87 Bi- and triantennary N-glycans 58:87 Bi- and triantennary N-glycans 58:87 Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans and exploring their activities against siglecs. 35149460 8 73 theme Explicit 1364:1371 arg1 recognition 1373:1383 Explicit recognition 1364:1383 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15 1364:1465 Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands. 35149460 0 74 theme regeneration 17:28 arg1 system 30:35 Sugar nucleotide regeneration system 0:35 Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans 0:87 Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans and exploring their activities against siglecs. 35149460 7 75 theme sequence 1220:1227 arg1 2,8 1250:1252 2,8 1250:1252 2,8 1250:1252 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 35149460 7 75 theme sequence 1220:1227 arg1 α 1248:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α 1204:1248 the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) 1204:1253 Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. 34939095 0 0 theme oligosaccharide 79:93 arg1 structure 107:115 the oligosaccharide common core structure 75:115 the oligosaccharide common core structure 75:115 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 34939095 4 1 theme nonstoichiometric 699:715 arg1 presence 717:724 the nonstoichiometric presence 695:724 the nonstoichiometric presence of three monosaccharides 695:749 This analysis identified three N-linked oligosaccharides that differ in the nonstoichiometric presence of three monosaccharides, with the largest oligosaccharide composed of eight residues organized in a highly branched fashion. 34939095 1 2 theme Paramecium 253:262 arg1 bursaria 264:271 the protozoan Paramecium bursaria 239:271 the protozoan Paramecium bursaria 239:271 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 1 3 theme bursaria 264:271 arg1 NC64A 218:222 Chlorella variabilis strain NC64A 190:222 Chlorella variabilis strain NC64A 190:222 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 1 3 theme bursaria 264:271 arg1 symbiont 227:234 a symbiont 225:234 a symbiont of the protozoan Paramecium bursaria 225:271 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 0 4 theme core 102:105 arg1 structure 107:115 the oligosaccharide common core structure 75:115 the oligosaccharide common core structure 75:115 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 34939095 7 5 theme region 1369:1374 arg1 features 1334:1341 the essential features 1320:1341 the essential features of the common core glycan region in the chloroviruses 1320:1395 This discovery means that we need to reconsider the essential features of the common core glycan region in the chloroviruses. 34939095 3 6 theme matrix-assisted 516:530 arg1 ionization-time 549:563 matrix-assisted laser desorption ionization-time 516:563 matrix-assisted laser desorption ionization-time of flight mass spectrometry 516:591 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 0 7 theme common 95:100 arg1 structure 107:115 the oligosaccharide common core structure 75:115 the oligosaccharide common core structure 75:115 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 34939095 3 8 theme laser 532:536 arg1 ionization-time 549:563 matrix-assisted laser desorption ionization-time 516:563 matrix-assisted laser desorption ionization-time of flight mass spectrometry 516:591 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 2 9 theme 339-kb 286:291 arg1 genome 293:298 a 339-kb genome 284:298 a 339-kb genome encoding ca. 366 proteins and 11 tRNAs 284:337 MA-1D has a 339-kb genome encoding ca. 366 proteins and 11 tRNAs. 34939095 5 10 theme other 922:926 arg1 chloroviruses 928:940 the other chloroviruses 918:940 the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses 918:1065 The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. 34939095 6 11 theme strong 1121:1126 arg1 homology 1128:1135 strong homology 1121:1135 strong homology to the putative xylosyltransferase 1121:1170 Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. 34939095 0 12 from MA-1D 51:55 arg1 N-glycans 0:8 N-glycans 0:8 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 0:116 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 34939095 6 13 theme chlorovirus 1189:1199 arg1 PBCV-1 1201:1206 the reference chlorovirus PBCV-1 1175:1206 the reference chlorovirus PBCV-1 1175:1206 Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. 34939095 6 14 theme genome 1093:1098 arg1 Examination 1068:1078 Examination 1068:1078 Examination of the MA-1D genome 1068:1098 Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. 34939095 0 15 theme structure 107:115 arg1 Re-evaluation 58:70 Re-evaluation 58:70 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 0:116 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 34939095 5 16 theme distal 966:971 arg1 unit 980:983 a distal xylose unit 964:983 a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses 964:1065 The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. 34939095 5 16 theme distal 966:971 arg1 part 1009:1012 part 1009:1012 part of a conserved core region for all the chloroviruses 1009:1065 The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. 34939095 6 17 theme MA-1D 1087:1091 arg1 genome 1093:1098 the MA-1D genome 1083:1098 the MA-1D genome 1083:1098 Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. 34939095 3 18 theme capsid 376:381 arg1 MCP 392:394 MCP 392:394 MCP 392:394 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 3 18 theme capsid 376:381 arg1 protein 383:389 its major capsid protein 366:389 its major capsid protein (MCP) 366:395 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 6 19 with gene 1111:1114 arg1 homology 1128:1135 strong homology 1121:1135 strong homology to the putative xylosyltransferase 1121:1170 Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. 34939095 6 20 theme stop 1260:1263 arg1 codon 1265:1269 a premature stop codon 1248:1269 a premature stop codon 1248:1269 Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. 34939095 4 21 theme largest 761:767 arg1 oligosaccharide 769:783 the largest oligosaccharide 757:783 the largest oligosaccharide composed of eight residues organized in a highly branched fashion 757:849 This analysis identified three N-linked oligosaccharides that differ in the nonstoichiometric presence of three monosaccharides, with the largest oligosaccharide composed of eight residues organized in a highly branched fashion. 34939095 1 22 theme Chlorella 190:198 arg1 NC64A 218:222 Chlorella variabilis strain NC64A 190:222 Chlorella variabilis strain NC64A 190:222 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 1 22 theme Chlorella 190:198 arg1 symbiont 227:234 a symbiont 225:234 a symbiont of the protozoan Paramecium bursaria 225:271 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 6 23 theme virus 1215:1219 arg1 NY-2A 1221:1225 virus NY-2A 1215:1225 virus NY-2A 1215:1225 Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. 34939095 2 24 contain has 280:282 arg2 genome 293:298 a 339-kb genome 284:298 a 339-kb genome encoding ca. 366 proteins and 11 tRNAs 284:337 MA-1D has a 339-kb genome encoding ca. 366 proteins and 11 tRNAs. 34939095 2 24 contain has 280:282 arg1 MA-1D 274:278 MA-1D 274:278 MA-1D 274:278 MA-1D has a 339-kb genome encoding ca. 366 proteins and 11 tRNAs. 34939095 6 25 theme premature 1250:1258 arg1 codon 1265:1269 a premature stop codon 1248:1269 a premature stop codon 1248:1269 Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. 34939095 3 26 theme flight 568:573 arg1 spectrometry 580:591 flight mass spectrometry 568:591 flight mass spectrometry 568:591 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 1 27 theme variabilis 200:209 arg1 NC64A 218:222 Chlorella variabilis strain NC64A 190:222 Chlorella variabilis strain NC64A 190:222 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 1 27 theme variabilis 200:209 arg1 symbiont 227:234 a symbiont 225:234 a symbiont of the protozoan Paramecium bursaria 225:271 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 0 28 theme bursaria 26:33 arg1 virus 45:49 Paramecium bursaria chlorella virus 15:49 Paramecium bursaria chlorella virus MA-1D 15:55 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 34939095 4 29 theme branched 834:841 arg1 fashion 843:849 a highly branched fashion 825:849 a highly branched fashion 825:849 This analysis identified three N-linked oligosaccharides that differ in the nonstoichiometric presence of three monosaccharides, with the largest oligosaccharide composed of eight residues organized in a highly branched fashion. 34939095 7 30 theme common 1350:1355 arg1 region 1369:1374 the common core glycan region 1346:1374 the common core glycan region 1346:1374 This discovery means that we need to reconsider the essential features of the common core glycan region in the chloroviruses. 34939095 3 31 theme desorption 538:547 arg1 ionization-time 549:563 matrix-assisted laser desorption ionization-time 516:563 matrix-assisted laser desorption ionization-time of flight mass spectrometry 516:591 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 1 32 theme strain 211:216 arg1 NC64A 218:222 Chlorella variabilis strain NC64A 190:222 Chlorella variabilis strain NC64A 190:222 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 1 32 theme strain 211:216 arg1 symbiont 227:234 a symbiont 225:234 a symbiont of the protozoan Paramecium bursaria 225:271 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 0 33 theme Paramecium 15:24 arg1 virus 45:49 Paramecium bursaria chlorella virus 15:49 Paramecium bursaria chlorella virus MA-1D 15:55 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 34939095 5 34 theme xylose 973:978 arg1 unit 980:983 a distal xylose unit 964:983 a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses 964:1065 The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. 34939095 5 34 theme xylose 973:978 arg1 part 1009:1012 part 1009:1012 part of a conserved core region for all the chloroviruses 1009:1065 The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. 34939095 6 35 theme putative 1144:1151 arg1 xylosyltransferase 1153:1170 the putative xylosyltransferase 1140:1170 the putative xylosyltransferase 1140:1170 Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. 34939095 3 36 theme major 370:374 arg1 MCP 392:394 MCP 392:394 MCP 392:394 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 3 36 theme major 370:374 arg1 protein 383:389 its major capsid protein 366:389 its major capsid protein (MCP) 366:395 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 0 37 theme virus 45:49 arg1 MA-1D 51:55 Paramecium bursaria chlorella virus MA-1D 15:55 Paramecium bursaria chlorella virus MA-1D 15:55 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 34939095 5 38 theme core 1029:1032 arg1 region 1034:1039 a conserved core region 1017:1039 a conserved core region for all the chloroviruses 1017:1065 The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. 34939095 7 39 theme essential 1324:1332 arg1 features 1334:1341 the essential features 1320:1341 the essential features of the common core glycan region in the chloroviruses 1320:1395 This discovery means that we need to reconsider the essential features of the common core glycan region in the chloroviruses. 34939095 4 40 theme N-linked 654:661 arg1 oligosaccharides 663:678 three N-linked oligosaccharides 648:678 three N-linked oligosaccharides that differ in the nonstoichiometric presence of three monosaccharides 648:749 This analysis identified three N-linked oligosaccharides that differ in the nonstoichiometric presence of three monosaccharides, with the largest oligosaccharide composed of eight residues organized in a highly branched fashion. 34939095 0 41 theme chlorella 35:43 arg1 virus 45:49 Paramecium bursaria chlorella virus 15:49 Paramecium bursaria chlorella virus MA-1D 15:55 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 34939095 5 42 theme region 1034:1039 arg1 unit 980:983 a distal xylose unit 964:983 a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses 964:1065 The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. 34939095 5 42 theme region 1034:1039 arg1 part 1009:1012 part 1009:1012 part of a conserved core region for all the chloroviruses 1009:1065 The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. 34939095 3 43 theme other 345:349 arg1 chloroviruses 351:363 other chloroviruses 345:363 other chloroviruses 345:363 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 3 44 theme mass 575:578 arg1 spectrometry 580:591 flight mass spectrometry 568:591 flight mass spectrometry 568:591 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 1 45 theme Paramecium 118:127 arg1 virus 148:152 Paramecium bursaria chlorella virus 118:152 Paramecium bursaria chlorella virus MA-1D 118:158 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 3 46 theme spectrometry 580:591 arg1 ionization-time 549:563 matrix-assisted laser desorption ionization-time 516:563 matrix-assisted laser desorption ionization-time of flight mass spectrometry 516:591 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 3 46 theme spectrometry 580:591 arg1 spectroscopy 499:510 nuclear magnetic spectroscopy 482:510 nuclear magnetic spectroscopy 482:510 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 1 47 theme bursaria 129:136 arg1 virus 148:152 Paramecium bursaria chlorella virus 118:152 Paramecium bursaria chlorella virus MA-1D 118:158 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 5 48 theme conserved 1019:1027 arg1 region 1034:1039 a conserved core region 1017:1039 a conserved core region for all the chloroviruses 1017:1065 The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. 34939095 4 49 theme monosaccharides 735:749 arg1 presence 717:724 the nonstoichiometric presence 695:724 the nonstoichiometric presence of three monosaccharides 695:749 This analysis identified three N-linked oligosaccharides that differ in the nonstoichiometric presence of three monosaccharides, with the largest oligosaccharide composed of eight residues organized in a highly branched fashion. 34939095 7 50 theme core 1357:1360 arg1 region 1369:1374 the common core glycan region 1346:1374 the common core glycan region 1346:1374 This discovery means that we need to reconsider the essential features of the common core glycan region in the chloroviruses. 34939095 4 51 link N-linked 654:661 arg1 oligosaccharides 663:678 three N-linked oligosaccharides 648:678 three N-linked oligosaccharides that differ in the nonstoichiometric presence of three monosaccharides 648:749 This analysis identified three N-linked oligosaccharides that differ in the nonstoichiometric presence of three monosaccharides, with the largest oligosaccharide composed of eight residues organized in a highly branched fashion. 34939095 1 52 theme chlorella 138:146 arg1 virus 148:152 Paramecium bursaria chlorella virus 118:152 Paramecium bursaria chlorella virus MA-1D 118:158 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 6 53 theme reference 1179:1187 arg1 PBCV-1 1201:1206 the reference chlorovirus PBCV-1 1175:1206 the reference chlorovirus PBCV-1 1175:1206 Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. 34939095 7 54 theme glycan 1362:1367 arg1 region 1369:1374 the common core glycan region 1346:1374 the common core glycan region 1346:1374 This discovery means that we need to reconsider the essential features of the common core glycan region in the chloroviruses. 34939095 1 55 theme virus 148:152 arg1 MA-1D 154:158 Paramecium bursaria chlorella virus MA-1D 118:158 Paramecium bursaria chlorella virus MA-1D 118:158 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 1 55 theme virus 148:152 arg1 chlorovirus 165:175 a chlorovirus 163:175 a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria 163:271 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 34939095 2 56 dep proteins 317:324 arg1 ca. 309:311 ca. 366 proteins and 11 tRNAs 309:337 ca. 366 proteins and 11 tRNAs 309:337 MA-1D has a 339-kb genome encoding ca. 366 proteins and 11 tRNAs. 34939095 5 57 theme several 887:893 arg1 features 895:902 several features 887:902 several features 887:902 The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. 34939095 3 58 theme MS/MS 604:608 arg1 experiments 610:620 MS/MS experiments 604:620 MS/MS experiments 604:620 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 3 59 theme nuclear 482:488 arg1 spectroscopy 499:510 nuclear magnetic spectroscopy 482:510 nuclear magnetic spectroscopy 482:510 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 0 60 dep N-glycans 0:8 arg1 Re-evaluation 58:70 Re-evaluation 58:70 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 0:116 N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure. 34939095 7 61 from features 1334:1341 arg1 chloroviruses 1383:1395 the chloroviruses 1379:1395 the chloroviruses 1379:1395 This discovery means that we need to reconsider the essential features of the common core glycan region in the chloroviruses. 34939095 3 62 theme magnetic 490:497 arg1 spectroscopy 499:510 nuclear magnetic spectroscopy 482:510 nuclear magnetic spectroscopy 482:510 Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. 34939095 1 63 theme protozoan 243:251 arg1 bursaria 264:271 the protozoan Paramecium bursaria 239:271 the protozoan Paramecium bursaria 239:271 Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. 36704963 7 0 theme complex 1534:1540 arg1 formation 1504:1512 the formation 1500:1512 the formation of the SNARE fusion complex 1500:1540 Accordingly, SM15 was found to enhance SNAP29 O-GlcNAcylation and, thereby, inhibit the formation of the SNARE fusion complex. 36704963 2 1 theme clear 345:349 arg1 understanding 363:375 a clear mechanistic understanding 343:375 a clear mechanistic understanding of their target action 343:398 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 7 2 theme SNARE 1521:1525 arg1 complex 1534:1540 the SNARE fusion complex 1517:1540 the SNARE fusion complex 1517:1540 Accordingly, SM15 was found to enhance SNAP29 O-GlcNAcylation and, thereby, inhibit the formation of the SNARE fusion complex. 36704963 6 3 theme component 1333:1341 arg1 SNAP29 1343:1348 the SNARE fusion complex component SNAP29 1308:1348 the SNARE fusion complex component SNAP29 1308:1348 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 3 4 theme cytotoxic 547:555 arg1 molecule 563:570 a previously identified cytotoxic small molecule 523:570 a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules 523:652 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 3 4 theme cytotoxic 547:555 arg1 SM15 573:576 SM15 573:576 SM15 573:576 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 8 5 theme cell 1753:1756 arg1 death 1758:1762 apoptotic cell death 1743:1762 apoptotic cell death 1743:1762 In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. 36704963 1 6 theme cancer 269:274 arg1 stage 276:280 the cancer stage 265:280 the cancer stage 265:280 Macroautophagy/autophagy has been shown to exert a dual role in cancer i.e., promoting cell survival or cell death depending on the cellular context and the cancer stage. 36704963 6 7 theme fusion 1318:1323 arg1 SNAP29 1343:1348 the SNARE fusion complex component SNAP29 1308:1348 the SNARE fusion complex component SNAP29 1308:1348 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 9 8 from intervention 1857:1868 arg1 cancer 1873:1878 cancer 1873:1878 cancer 1873:1878 Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases. 36704963 9 8 from intervention 1857:1868 arg1 diseases 1911:1918 other autophagy-associated diseases 1884:1918 other autophagy-associated diseases 1884:1918 Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases. 36704963 4 9 theme autophagic 858:867 arg1 flux 869:872 basal autophagic flux 852:872 basal autophagic flux 852:872 By using several biochemical and cell biology assays we demonstrated that SM15 blocks basal autophagic flux by inhibiting the fusion of correctly formed autophagosomes with lysosomes. 36704963 6 10 theme N-acetylglucosamine 1210:1228 arg1 OGT 1196:1198 OGT 1196:1198 OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) 1196:1250 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 6 10 theme N-acetylglucosamine 1210:1228 arg1 transferase 1239:1249 O-linked N-acetylglucosamine (GlcNAc) transferase 1201:1249 O-linked N-acetylglucosamine (GlcNAc) transferase 1201:1249 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 3 11 theme autophagy 745:753 arg1 molecule 719:726 the molecule 715:726 the molecule 715:726 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 3 11 theme autophagy 745:753 arg1 inhibitor 755:763 a potent autophagy inhibitor 736:763 a potent autophagy inhibitor 736:763 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 2 12 theme potent 309:314 arg1 modulators 326:335 potent autophagy modulators 309:335 potent autophagy modulators 309:335 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 1 13 theme cell 199:202 arg1 survival 204:211 cell survival 199:211 cell survival 199:211 Macroautophagy/autophagy has been shown to exert a dual role in cancer i.e., promoting cell survival or cell death depending on the cellular context and the cancer stage. 36704963 3 14 theme molecule 563:570 arg1 action 513:518 action 513:518 action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules 513:652 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 6 15 theme molecular 1377:1385 arg1 target 1387:1392 the molecular target 1373:1392 the molecular target of SM15 in autophagy 1373:1413 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 6 16 theme O-GlcNAcylation-defective 1272:1296 arg1 mutant 1298:1303 an O-GlcNAcylation-defective mutant 1269:1303 an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29 1269:1348 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 2 17 contain has 401:403 arg2 importance 415:424 paramount importance 405:424 paramount importance 405:424 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 2 17 contain has 401:403 arg1 development 294:304 development 294:304 development of potent autophagy modulators, with a clear mechanistic understanding of their target action, 294:399 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 8 18 from pathway 1588:1594 arg1 autophagy 1599:1607 autophagy 1599:1607 autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation 1599:1699 In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. 36704963 4 19 theme formed 912:917 arg1 autophagosomes 919:932 correctly formed autophagosomes 902:932 correctly formed autophagosomes 902:932 By using several biochemical and cell biology assays we demonstrated that SM15 blocks basal autophagic flux by inhibiting the fusion of correctly formed autophagosomes with lysosomes. 36704963 3 20 theme interaction 619:629 arg1 microtubules 641:652 microtubules 641:652 microtubules 641:652 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 3 20 theme interaction 619:629 arg1 domain 631:636 the interaction domain 615:636 the interaction domain of microtubules 615:652 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 9 21 theme SNAP29 1793:1798 arg1 activity 1800:1807 SNAP29 activity 1793:1807 SNAP29 activity 1793:1807 Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases. 36704963 7 22 dep enhance 1447:1453 arg1 inhibit 1492:1498 inhibit 1492:1498 inhibit the formation of the SNARE fusion complex 1492:1540 Accordingly, SM15 was found to enhance SNAP29 O-GlcNAcylation and, thereby, inhibit the formation of the SNARE fusion complex. 36704963 0 23 theme ROS 96:98 arg1 production 100:109 ROS production 96:109 ROS production 96:109 Blockage of autophagosome-lysosome fusion through SNAP29 O-GlcNAcylation promotes apoptosis via ROS production. 36704963 6 24 from autophagy 1405:1413 arg1 target 1387:1392 the molecular target 1373:1392 the molecular target of SM15 in autophagy 1373:1413 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 5 25 theme apoptosis-mediated 997:1014 arg1 death 1021:1025 apoptosis-mediated cell death 997:1025 apoptosis-mediated cell death associated with ROS production 997:1056 SM15-induced autophagic flux blockage promoted apoptosis-mediated cell death associated with ROS production. 36704963 6 26 theme ROS 1124:1126 arg1 production 1128:1137 ROS production 1124:1137 ROS production 1124:1137 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 2 27 theme clinical 450:457 arg1 studies 459:465 both mechanistic and clinical studies 429:465 both mechanistic and clinical studies 429:465 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 2 28 theme target 386:391 arg1 action 393:398 their target action 380:398 their target action 380:398 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 6 29 from target 1387:1392 arg1 autophagy 1405:1413 autophagy 1405:1413 autophagy 1405:1413 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 5 30 theme autophagic 963:972 arg1 blockage 979:986 SM15-induced autophagic flux blockage 950:986 SM15-induced autophagic flux blockage 950:986 SM15-induced autophagic flux blockage promoted apoptosis-mediated cell death associated with ROS production. 36704963 2 31 theme mechanistic 434:444 arg1 studies 459:465 both mechanistic and clinical studies 429:465 both mechanistic and clinical studies 429:465 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 8 32 theme new 1584:1586 arg1 pathway 1588:1594 a new pathway 1582:1594 a new pathway 1582:1594 In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. 36704963 0 33 theme autophagosome-lysosome 12:33 arg1 fusion 35:40 autophagosome-lysosome fusion 12:40 autophagosome-lysosome fusion 12:40 Blockage of autophagosome-lysosome fusion through SNAP29 O-GlcNAcylation promotes apoptosis via ROS production. 36704963 6 34 from SM15 1397:1400 arg1 autophagy 1405:1413 autophagy 1405:1413 autophagy 1405:1413 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 2 35 theme paramount 405:413 arg1 importance 415:424 paramount importance 405:424 paramount importance 405:424 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 6 36 theme flux 1085:1088 arg1 blockage 1090:1097 autophagic flux blockage 1074:1097 autophagic flux blockage 1074:1097 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 9 37 theme autophagy-associated 1890:1909 arg1 diseases 1911:1918 other autophagy-associated diseases 1884:1918 other autophagy-associated diseases 1884:1918 Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases. 36704963 8 38 theme autophagic 1645:1654 arg1 blockage 1661:1668 autophagic flux blockage 1645:1668 autophagic flux blockage 1645:1668 In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. 36704963 3 39 theme kinetochore 662:672 arg1 NDC80/HEC1 684:693 the kinetochore component NDC80/HEC1 658:693 the kinetochore component NDC80/HEC1 658:693 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 4 40 theme biology 804:810 arg1 assays 812:817 several biochemical and cell biology assays 775:817 assays 812:817 By using several biochemical and cell biology assays we demonstrated that SM15 blocks basal autophagic flux by inhibiting the fusion of correctly formed autophagosomes with lysosomes. 36704963 3 41 theme action 513:518 arg1 mechanism 500:508 the mechanism 496:508 the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules 496:652 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 3 41 theme action 513:518 arg1 NDC80/HEC1 684:693 the kinetochore component NDC80/HEC1 658:693 the kinetochore component NDC80/HEC1 658:693 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 7 42 theme fusion 1527:1532 arg1 complex 1534:1540 the SNARE fusion complex 1517:1540 the SNARE fusion complex 1517:1540 Accordingly, SM15 was found to enhance SNAP29 O-GlcNAcylation and, thereby, inhibit the formation of the SNARE fusion complex. 36704963 2 43 theme mechanistic 351:361 arg1 understanding 363:375 a clear mechanistic understanding 343:375 a clear mechanistic understanding of their target action 343:398 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 8 44 theme autophagosome 1674:1686 arg1 accumulation 1688:1699 autophagosome accumulation 1674:1699 autophagosome accumulation 1674:1699 In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. 36704963 6 45 theme SNAP29 1343:1348 arg1 mutant 1298:1303 an O-GlcNAcylation-defective mutant 1269:1303 an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29 1269:1348 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 3 46 theme identified 536:545 arg1 molecule 563:570 a previously identified cytotoxic small molecule 523:570 a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules 523:652 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 3 46 theme identified 536:545 arg1 SM15 573:576 SM15 573:576 SM15 573:576 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 7 47 theme SNAP29 1455:1460 arg1 O-GlcNAcylation 1462:1476 SNAP29 O-GlcNAcylation 1455:1476 SNAP29 O-GlcNAcylation 1455:1476 Accordingly, SM15 was found to enhance SNAP29 O-GlcNAcylation and, thereby, inhibit the formation of the SNARE fusion complex. 36704963 6 48 theme complex 1325:1331 arg1 SNAP29 1343:1348 the SNARE fusion complex component SNAP29 1308:1348 the SNARE fusion complex component SNAP29 1308:1348 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 8 49 theme apoptotic 1743:1751 arg1 death 1758:1762 apoptotic cell death 1743:1762 apoptotic cell death 1743:1762 In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. 36704963 6 50 theme SNARE 1312:1316 arg1 SNAP29 1343:1348 the SNARE fusion complex component SNAP29 1308:1348 the SNARE fusion complex component SNAP29 1308:1348 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 2 51 theme autophagy 316:324 arg1 modulators 326:335 potent autophagy modulators 309:335 potent autophagy modulators 309:335 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 4 52 theme basal 852:856 arg1 flux 869:872 basal autophagic flux 852:872 basal autophagic flux 852:872 By using several biochemical and cell biology assays we demonstrated that SM15 blocks basal autophagic flux by inhibiting the fusion of correctly formed autophagosomes with lysosomes. 36704963 6 53 theme O-linked 1201:1208 arg1 GlcNAc 1231:1236 GlcNAc 1231:1236 GlcNAc 1231:1236 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 6 53 theme O-linked 1201:1208 arg1 N-acetylglucosamine 1210:1228 O-linked N-acetylglucosamine 1201:1228 O-linked N-acetylglucosamine (GlcNAc) transferase 1201:1249 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 6 54 theme SM15 1397:1400 arg1 target 1387:1392 the molecular target 1373:1392 the molecular target of SM15 in autophagy 1373:1413 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 3 55 theme small 557:561 arg1 molecule 563:570 a previously identified cytotoxic small molecule 523:570 a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules 523:652 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 3 55 theme small 557:561 arg1 SM15 573:576 SM15 573:576 SM15 573:576 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 4 56 theme autophagosomes 919:932 arg1 fusion 892:897 the fusion 888:897 the fusion of correctly formed autophagosomes with lysosomes 888:947 By using several biochemical and cell biology assays we demonstrated that SM15 blocks basal autophagic flux by inhibiting the fusion of correctly formed autophagosomes with lysosomes. 36704963 6 57 theme OGT 1196:1198 arg1 inhibition 1182:1191 genetic or pharmacological inhibition 1155:1191 genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) 1155:1250 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 3 58 theme potent 738:743 arg1 molecule 719:726 the molecule 715:726 the molecule 715:726 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 3 58 theme potent 738:743 arg1 inhibitor 755:763 a potent autophagy inhibitor 736:763 a potent autophagy inhibitor 736:763 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 1 59 theme cell 216:219 arg1 death 221:225 cell death 216:225 cell death 216:225 Macroautophagy/autophagy has been shown to exert a dual role in cancer i.e., promoting cell survival or cell death depending on the cellular context and the cancer stage. 36704963 6 60 theme autophagic 1074:1083 arg1 blockage 1090:1097 autophagic flux blockage 1074:1097 autophagic flux blockage 1074:1097 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 1 61 theme dual 163:166 arg1 role 168:171 a dual role 161:171 a dual role 161:171 Macroautophagy/autophagy has been shown to exert a dual role in cancer i.e., promoting cell survival or cell death depending on the cellular context and the cancer stage. 36704963 9 62 theme activity 1800:1807 arg1 modulation 1779:1788 modulation 1779:1788 modulation of SNAP29 activity 1779:1807 Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases. 36704963 9 63 theme new 1825:1827 arg1 opportunity 1829:1839 a new opportunity 1823:1839 a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases 1823:1918 Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases. 36704963 6 64 link O-linked 1201:1208 arg1 GlcNAc 1231:1236 GlcNAc 1231:1236 GlcNAc 1231:1236 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 6 64 link O-linked 1201:1208 arg1 N-acetylglucosamine 1210:1228 O-linked N-acetylglucosamine 1201:1228 O-linked N-acetylglucosamine (GlcNAc) transferase 1201:1249 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 5 65 theme cell 1016:1019 arg1 death 1021:1025 apoptosis-mediated cell death 997:1025 apoptosis-mediated cell death associated with ROS production 997:1056 SM15-induced autophagic flux blockage promoted apoptosis-mediated cell death associated with ROS production. 36704963 2 66 theme action 393:398 arg1 understanding 363:375 a clear mechanistic understanding 343:375 a clear mechanistic understanding of their target action 343:398 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 5 67 theme SM15-induced 950:961 arg1 blockage 979:986 SM15-induced autophagic flux blockage 950:986 SM15-induced autophagic flux blockage 950:986 SM15-induced autophagic flux blockage promoted apoptosis-mediated cell death associated with ROS production. 36704963 0 68 theme fusion 35:40 arg1 Blockage 0:7 Blockage 0:7 Blockage of autophagosome-lysosome fusion through SNAP29 O-GlcNAcylation 0:71 Blockage of autophagosome-lysosome fusion through SNAP29 O-GlcNAcylation promotes apoptosis via ROS production. 36704963 5 69 theme flux 974:977 arg1 blockage 979:986 SM15-induced autophagic flux blockage 950:986 SM15-induced autophagic flux blockage 950:986 SM15-induced autophagic flux blockage promoted apoptosis-mediated cell death associated with ROS production. 36704963 6 70 theme apoptosis 1100:1108 arg1 induction 1110:1118 apoptosis induction 1100:1118 apoptosis induction 1100:1118 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 3 71 theme microtubules 641:652 arg1 microtubules 641:652 microtubules 641:652 microtubules 641:652 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 3 71 theme microtubules 641:652 arg1 domain 631:636 the interaction domain 615:636 the interaction domain of microtubules 615:652 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 3 71 theme microtubules 641:652 arg1 microtubules 598:609 microtubules 598:609 microtubules 598:609 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 2 72 with modulators 326:335 arg1 understanding 363:375 a clear mechanistic understanding 343:375 a clear mechanistic understanding of their target action 343:398 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 4 73 with fusion 892:897 arg1 lysosomes 939:947 lysosomes 939:947 lysosomes 939:947 By using several biochemical and cell biology assays we demonstrated that SM15 blocks basal autophagic flux by inhibiting the fusion of correctly formed autophagosomes with lysosomes. 36704963 9 74 theme other 1884:1888 arg1 diseases 1911:1918 other autophagy-associated diseases 1884:1918 other autophagy-associated diseases 1884:1918 Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases. 36704963 8 75 theme O-GlcNAcylated 1620:1633 arg1 SNAP29 1635:1640 O-GlcNAcylated SNAP29 1620:1640 O-GlcNAcylated SNAP29 1620:1640 In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. 36704963 3 76 theme component 674:682 arg1 NDC80/HEC1 684:693 the kinetochore component NDC80/HEC1 658:693 the kinetochore component NDC80/HEC1 658:693 In the process of exploring the mechanism of action of a previously identified cytotoxic small molecule (SM15) designed to target microtubules and the interaction domain of microtubules and the kinetochore component NDC80/HEC1, we discovered that the molecule acts as a potent autophagy inhibitor. 36704963 6 77 theme pharmacological 1166:1180 arg1 inhibition 1182:1191 genetic or pharmacological inhibition 1155:1191 genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) 1155:1250 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 8 78 theme flux 1656:1659 arg1 blockage 1661:1668 autophagic flux blockage 1645:1668 autophagic flux blockage 1645:1668 In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. 36704963 2 79 theme modulators 326:335 arg1 development 294:304 development 294:304 development of potent autophagy modulators, with a clear mechanistic understanding of their target action, 294:399 Therefore, development of potent autophagy modulators, with a clear mechanistic understanding of their target action, has paramount importance in both mechanistic and clinical studies. 36704963 5 80 theme ROS 1043:1045 arg1 production 1047:1056 ROS production 1043:1056 ROS production 1043:1056 SM15-induced autophagic flux blockage promoted apoptosis-mediated cell death associated with ROS production. 36704963 6 81 theme genetic 1155:1161 arg1 inhibition 1182:1191 genetic or pharmacological inhibition 1155:1191 genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) 1155:1250 Interestingly, autophagic flux blockage, apoptosis induction and ROS production were rescued by genetic or pharmacological inhibition of OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) or by expressing an O-GlcNAcylation-defective mutant of the SNARE fusion complex component SNAP29, pointing to SNAP29 as the molecular target of SM15 in autophagy. 36704963 4 82 theme cell 799:802 arg1 assays 812:817 several biochemical and cell biology assays 775:817 assays 812:817 By using several biochemical and cell biology assays we demonstrated that SM15 blocks basal autophagic flux by inhibiting the fusion of correctly formed autophagosomes with lysosomes. 36704963 9 83 theme therapeutic 1845:1855 arg1 intervention 1857:1868 therapeutic intervention 1845:1868 therapeutic intervention in cancer and other autophagy-associated diseases 1845:1918 Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases. 36704963 8 84 theme ROS 1724:1726 arg1 production 1728:1737 ROS production 1724:1737 ROS production 1724:1737 In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. 36704963 1 85 theme cellular 244:251 arg1 context 253:259 the cellular context 240:259 the cellular context 240:259 Macroautophagy/autophagy has been shown to exert a dual role in cancer i.e., promoting cell survival or cell death depending on the cellular context and the cancer stage. 36690170 7 0 theme O-GlcNAcylation 1408:1422 arg1 Inhibition 1382:1391 Inhibition 1382:1391 Inhibition of the HBP and O-GlcNAcylation 1382:1422 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 14 1 theme greater 2617:2623 arg1 capacity 2644:2651 greater aerobic glycolytic capacity 2617:2651 greater aerobic glycolytic capacity than GCs from large antral follicles 2617:2688 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 9 2 theme antral 1799:1804 arg1 follicles 1806:1814 small antral follicles 1793:1814 small antral follicles 1793:1814 Interestingly, inhibition of cellular respiration by 2-Deoxy-D-glucose impaired OCR only in GCs from small antral follicles, but exposure to the mitochondrial stress test had no effect. 36690170 12 3 theme small 2306:2310 arg1 follicles 2319:2327 small antral follicles 2306:2327 small antral follicles 2306:2327 Inhibition of O-GlcNAcylation impaired the expression of hexokinase only in GCs of small antral follicles. 36690170 7 4 theme HBP 1400:1402 arg1 Inhibition 1382:1391 Inhibition 1382:1391 Inhibition of the HBP and O-GlcNAcylation 1382:1422 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 9 5 from follicles 1806:1814 arg1 GCs 1784:1786 GCs 1784:1786 GCs from small antral follicles 1784:1814 Interestingly, inhibition of cellular respiration by 2-Deoxy-D-glucose impaired OCR only in GCs from small antral follicles, but exposure to the mitochondrial stress test had no effect. 36690170 12 6 theme follicles 2319:2327 arg1 GCs 2299:2301 GCs 2299:2301 GCs of small antral follicles 2299:2327 Inhibition of O-GlcNAcylation impaired the expression of hexokinase only in GCs of small antral follicles. 36690170 9 7 contain had 1863:1865 arg1 exposure 1821:1828 exposure 1821:1828 exposure to the mitochondrial stress test 1821:1861 Interestingly, inhibition of cellular respiration by 2-Deoxy-D-glucose impaired OCR only in GCs from small antral follicles, but exposure to the mitochondrial stress test had no effect. 36690170 9 7 contain had 1863:1865 arg2 effect 1870:1875 no effect 1867:1875 no effect 1867:1875 Interestingly, inhibition of cellular respiration by 2-Deoxy-D-glucose impaired OCR only in GCs from small antral follicles, but exposure to the mitochondrial stress test had no effect. 36690170 3 8 from % 499:499 arg1 cells 519:523 cells 519:523 cells 519:523 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 7 9 from activity 1455:1462 arg1 type 1483:1486 either type 1476:1486 either type of follicle 1476:1498 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 10 10 theme concomitant 2018:2028 arg1 increase 2030:2037 a concomitant increase 2016:2037 a concomitant increase in glycolytic metabolism 2016:2062 Conversely, in GCs from large antral follicles, oxidative metabolism was impaired by the mitochondrial stress test and was accompanied by a concomitant increase in glycolytic metabolism. 36690170 3 11 from metabolism 600:609 arg1 GCs 621:623 bovine GCs 614:623 bovine GCs 614:623 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 2 12 theme utilization 262:272 arg1 Disruption 240:249 Disruption 240:249 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) 240:318 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 1 13 theme follicles 163:171 arg1 GCs 147:149 GCs 147:149 GCs 147:149 Granulosa cells (GCs) of ovarian follicles prefer glucose as a metabolic substrate for growth and maturation. 36690170 1 13 theme follicles 163:171 arg1 cells 140:144 Granulosa cells 130:144 Granulosa cells (GCs) of ovarian follicles 130:171 Granulosa cells (GCs) of ovarian follicles prefer glucose as a metabolic substrate for growth and maturation. 36690170 14 14 theme antral 2592:2597 arg1 follicles 2599:2607 small antral follicles 2586:2607 small antral follicles 2586:2607 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 14 15 theme metabolic 2764:2772 arg1 activity 2774:2781 metabolic activity 2764:2781 metabolic activity 2764:2781 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 9 16 theme stress 1851:1856 arg1 test 1858:1861 the mitochondrial stress test 1833:1861 the mitochondrial stress test 1833:1861 Interestingly, inhibition of cellular respiration by 2-Deoxy-D-glucose impaired OCR only in GCs from small antral follicles, but exposure to the mitochondrial stress test had no effect. 36690170 3 17 used utilized 528:535 arg2 % 499:499 2-5% 496:499 2-5% of all glucose in cells 496:523 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 3 17 used utilized 528:535 arg2 glucose 508:514 all glucose 504:514 all glucose in cells 504:523 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 2 18 theme biosynthesis 293:304 arg1 pathway 306:312 the hexosamine biosynthesis pathway 278:312 the hexosamine biosynthesis pathway (HBP) 278:318 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 2 18 theme biosynthesis 293:304 arg1 HBP 315:317 HBP 315:317 HBP 315:317 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 12 19 theme hexokinase 2280:2289 arg1 expression 2266:2275 the expression 2262:2275 the expression of hexokinase only in GCs of small antral follicles 2262:2327 Inhibition of O-GlcNAcylation impaired the expression of hexokinase only in GCs of small antral follicles. 36690170 5 20 dep HBP 916:918 arg1 the 912:914 the 912:914 the 912:914 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 6 21 theme small 1237:1241 arg1 follicles 1250:1258 small antral follicles 1237:1258 small antral follicles 1237:1258 GCs from small antral follicles exhibited overall greater metabolic activity than GCs from large antral follicles as evidenced by increased ECAR and OCR. 36690170 5 22 theme glycolysis 1006:1015 arg1 indicator 993:1001 an indicator 990:1001 ECAR; an indicator of glycolysis 984:1015 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 9 23 theme cellular 1721:1728 arg1 respiration 1730:1740 cellular respiration 1721:1740 cellular respiration 1721:1740 Interestingly, inhibition of cellular respiration by 2-Deoxy-D-glucose impaired OCR only in GCs from small antral follicles, but exposure to the mitochondrial stress test had no effect. 36690170 4 24 theme n = 10 839:844 arg1 pairs 852:856 n = 10 ovary pairs 839:856 n = 10 ovary pairs 839:856 The GCs were initially cultured in serum-containing medium to confluency and then sub-cultured in serum-free medium in 96 well plates (n = 10 ovary pairs). 36690170 4 24 theme n = 10 839:844 arg1 plates 831:836 96 well plates 823:836 96 well plates (n = 10 ovary pairs) 823:857 The GCs were initially cultured in serum-containing medium to confluency and then sub-cultured in serum-free medium in 96 well plates (n = 10 ovary pairs). 36690170 6 25 from follicles 1332:1340 arg1 GCs 1310:1312 GCs 1310:1312 GCs from large antral follicles 1310:1340 GCs from small antral follicles exhibited overall greater metabolic activity than GCs from large antral follicles as evidenced by increased ECAR and OCR. 36690170 2 26 theme glucose 254:260 arg1 utilization 262:272 glucose utilization 254:272 glucose utilization 254:272 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 13 27 from expression 2378:2387 arg1 GCs 2459:2461 GCs 2459:2461 GCs of both types of follicles 2459:2488 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 13 28 theme dehydrogenase 2442:2454 arg1 expression 2378:2387 the expression 2374:2387 the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles 2374:2488 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 0 29 from metabolism 92:101 arg1 cells 123:127 bovine granulosa cells 106:127 bovine granulosa cells 106:127 Evaluating the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells. 36690170 5 30 theme stress 1214:1219 arg1 tests 1221:1225 glycolytic and mitochondrial stress tests 1185:1225 glycolytic and mitochondrial stress tests 1185:1225 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 10 31 theme antral 1908:1913 arg1 follicles 1915:1923 large antral follicles 1902:1923 large antral follicles 1902:1923 Conversely, in GCs from large antral follicles, oxidative metabolism was impaired by the mitochondrial stress test and was accompanied by a concomitant increase in glycolytic metabolism. 36690170 7 32 theme follicle 1491:1498 arg1 type 1483:1486 either type 1476:1486 either type of follicle 1476:1498 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 2 33 theme follicles 472:480 arg1 GCs 418:420 bovine GCs 411:420 bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles 411:480 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 0 34 from impact 15:20 arg1 metabolism 92:101 glucose metabolism 84:101 glucose metabolism in bovine granulosa cells 84:127 Evaluating the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells. 36690170 3 35 from glucose 508:514 arg1 cells 519:523 cells 519:523 cells 519:523 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 11 36 theme antral 2177:2182 arg1 follicles 2184:2192 small antral follicles 2171:2192 small antral follicles 2171:2192 Immunodetection of glycolytic enzymes revealed that phosphofructokinase expression is increased in GCs of small antral follicles compared to large follicles. 36690170 8 37 dep HBP 1647:1649 arg1 the 1643:1645 the 1643:1645 the 1643:1645 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36690170 3 38 from cells 519:523 arg1 % 499:499 2-5% 496:499 2-5% of all glucose in cells 496:523 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 3 38 from cells 519:523 arg1 glucose 508:514 all glucose 504:514 all glucose in cells 504:523 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 6 39 theme metabolic 1286:1294 arg1 activity 1296:1303 overall greater metabolic activity 1270:1303 overall greater metabolic activity than GCs from large antral follicles 1270:1340 GCs from small antral follicles exhibited overall greater metabolic activity than GCs from large antral follicles as evidenced by increased ECAR and OCR. 36690170 13 40 theme phosphofructokinase 2392:2410 arg1 expression 2378:2387 the expression 2374:2387 the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles 2374:2488 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 2 41 theme bovine 411:416 arg1 GCs 418:420 bovine GCs 411:420 bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles 411:480 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 0 42 theme bovine 106:111 arg1 cells 123:127 bovine granulosa cells 106:127 bovine granulosa cells 106:127 Evaluating the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells. 36690170 5 43 theme consumption 1029:1039 arg1 OCR 1047:1049 OCR 1047:1049 OCR; an indicator of oxidative phosphorylation 1047:1092 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 5 43 theme consumption 1029:1039 arg1 rate 1041:1044 oxygen consumption rate 1022:1044 oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs 1022:1104 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 13 44 theme pyruvate 2413:2420 arg1 kinase 2422:2427 pyruvate kinase 2413:2427 pyruvate kinase 2413:2427 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 11 45 theme glycolytic 2084:2093 arg1 enzymes 2095:2101 glycolytic enzymes 2084:2101 glycolytic enzymes 2084:2101 Immunodetection of glycolytic enzymes revealed that phosphofructokinase expression is increased in GCs of small antral follicles compared to large follicles. 36690170 5 46 theme GCs 1102:1104 arg1 OCR 1047:1049 OCR 1047:1049 OCR; an indicator of oxidative phosphorylation 1047:1092 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 5 46 theme GCs 1102:1104 arg1 rate 1041:1044 oxygen consumption rate 1022:1044 oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs 1022:1104 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 5 46 theme GCs 1102:1104 arg1 ECAR 984:987 ECAR 984:987 ECAR; an indicator of glycolysis 984:1015 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 5 46 theme GCs 1102:1104 arg1 rate 978:981 24 h. Extracellular acidification rate 944:981 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) 944:1016 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 0 47 theme O-GlcNAcylation 65:79 arg1 impact 15:20 the impact 11:20 the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells 11:127 Evaluating the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells. 36690170 13 48 theme dehydrogenase 2538:2550 arg1 expression 2516:2525 the expression 2512:2525 the expression of lactate dehydrogenase 2512:2550 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 14 49 contain has 2737:2739 arg1 disruption 2695:2704 disruption 2695:2704 disruption of the HBP and O-GlcNAcylation 2695:2735 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 14 49 contain has 2737:2739 arg2 little 2741:2746 little 2741:2746 little 2741:2746 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 2 50 theme 3-5 mm 437:442 arg1 GCs 418:420 bovine GCs 411:420 bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles 411:480 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 11 51 theme phosphofructokinase 2117:2135 arg1 expression 2137:2146 phosphofructokinase expression 2117:2146 phosphofructokinase expression 2117:2146 Immunodetection of glycolytic enzymes revealed that phosphofructokinase expression is increased in GCs of small antral follicles compared to large follicles. 36690170 5 52 dep OCR 1047:1049 arg1 indicator 1055:1063 an indicator 1052:1063 OCR; an indicator of oxidative phosphorylation 1047:1092 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 14 53 from follicles 2680:2688 arg1 GCs 2658:2660 GCs 2658:2660 GCs from large antral follicles 2658:2688 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 12 54 from expression 2266:2275 arg1 GCs 2299:2301 GCs 2299:2301 GCs of small antral follicles 2299:2327 Inhibition of O-GlcNAcylation impaired the expression of hexokinase only in GCs of small antral follicles. 36690170 7 55 from type 1483:1486 arg1 GCs 1467:1469 GCs 1467:1469 GCs from either type of follicle 1467:1498 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 7 55 from type 1483:1486 arg1 activity 1455:1462 the metabolic activity 1441:1462 the metabolic activity of GCs from either type of follicle 1441:1498 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 5 56 theme Extracellular 950:962 arg1 ECAR 984:987 ECAR 984:987 ECAR; an indicator of glycolysis 984:1015 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 5 56 theme Extracellular 950:962 arg1 rate 978:981 24 h. Extracellular acidification rate 944:981 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) 944:1016 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 14 57 theme large 2667:2671 arg1 follicles 2680:2688 large antral follicles 2667:2688 large antral follicles 2667:2688 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 10 58 from increase 2030:2037 arg1 metabolism 2053:2062 glycolytic metabolism 2042:2062 glycolytic metabolism 2042:2062 Conversely, in GCs from large antral follicles, oxidative metabolism was impaired by the mitochondrial stress test and was accompanied by a concomitant increase in glycolytic metabolism. 36690170 0 59 theme biosynthesis 40:51 arg1 pathway 53:59 the hexosamine biosynthesis pathway 25:59 the hexosamine biosynthesis pathway 25:59 Evaluating the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells. 36690170 5 60 theme oxidative 1068:1076 arg1 phosphorylation 1078:1092 oxidative phosphorylation 1068:1092 oxidative phosphorylation 1068:1092 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 13 61 theme O-GlcNAcylation 2344:2358 arg1 Inhibition 2330:2339 Inhibition 2330:2339 Inhibition of O-GlcNAcylation 2330:2358 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 10 62 theme stress 1981:1986 arg1 test 1988:1991 the mitochondrial stress test 1963:1991 the mitochondrial stress test 1963:1991 Conversely, in GCs from large antral follicles, oxidative metabolism was impaired by the mitochondrial stress test and was accompanied by a concomitant increase in glycolytic metabolism. 36690170 13 63 contain had 2495:2497 arg2 effect 2502:2507 no effect 2499:2507 no effect 2499:2507 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 13 63 contain had 2495:2497 arg1 Inhibition 2330:2339 Inhibition 2330:2339 Inhibition of O-GlcNAcylation 2330:2358 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 5 64 theme Seahorse 1128:1135 arg1 Analyzer 1143:1150 a Seahorse xFe96 Analyzer 1126:1150 a Seahorse xFe96 Analyzer 1126:1150 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 3 65 theme glucose 508:514 arg1 % 499:499 2-5% 496:499 2-5% of all glucose in cells 496:523 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 3 65 theme glucose 508:514 arg1 glucose 508:514 all glucose 504:514 all glucose in cells 504:523 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 8 66 theme glycolytic 1505:1514 arg1 test 1523:1526 The glycolytic stress test 1501:1526 The glycolytic stress test 1501:1526 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36690170 3 67 theme bovine 614:619 arg1 GCs 621:623 bovine GCs 614:623 bovine GCs 614:623 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 7 68 contain had 1424:1426 arg1 Inhibition 1382:1391 Inhibition 1382:1391 Inhibition of the HBP and O-GlcNAcylation 1382:1422 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 7 68 contain had 1424:1426 arg2 effect 1431:1436 no effect 1428:1436 no effect 1428:1436 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 14 69 theme aerobic 2625:2631 arg1 capacity 2644:2651 greater aerobic glycolytic capacity 2617:2651 greater aerobic glycolytic capacity than GCs from large antral follicles 2617:2688 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 9 70 theme small 1793:1797 arg1 follicles 1806:1814 small antral follicles 1793:1814 small antral follicles 1793:1814 Interestingly, inhibition of cellular respiration by 2-Deoxy-D-glucose impaired OCR only in GCs from small antral follicles, but exposure to the mitochondrial stress test had no effect. 36690170 8 71 theme additional 1586:1595 arg1 capacity 1608:1615 additional glycolytic capacity 1586:1615 additional glycolytic capacity 1586:1615 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36690170 2 72 link O-linked 328:335 arg1 O-GlcNAcylation 364:378 O-GlcNAcylation 364:378 O-GlcNAcylation 364:378 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 2 72 link O-linked 328:335 arg1 N-acetylglucosaminylation 337:361 O-linked N-acetylglucosaminylation 328:361 O-linked N-acetylglucosaminylation (O-GlcNAcylation) 328:379 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 2 73 theme hexosamine 282:291 arg1 pathway 306:312 the hexosamine biosynthesis pathway 278:312 the hexosamine biosynthesis pathway (HBP) 278:318 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 2 73 theme hexosamine 282:291 arg1 HBP 315:317 HBP 315:317 HBP 315:317 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 4 74 theme well 826:829 arg1 pairs 852:856 n = 10 ovary pairs 839:856 n = 10 ovary pairs 839:856 The GCs were initially cultured in serum-containing medium to confluency and then sub-cultured in serum-free medium in 96 well plates (n = 10 ovary pairs). 36690170 4 74 theme well 826:829 arg1 plates 831:836 96 well plates 823:836 96 well plates (n = 10 ovary pairs) 823:857 The GCs were initially cultured in serum-containing medium to confluency and then sub-cultured in serum-free medium in 96 well plates (n = 10 ovary pairs). 36690170 11 75 theme large 2206:2210 arg1 follicles 2212:2220 large follicles 2206:2220 large follicles 2206:2220 Immunodetection of glycolytic enzymes revealed that phosphofructokinase expression is increased in GCs of small antral follicles compared to large follicles. 36690170 5 76 dep ECAR 984:987 arg1 indicator 993:1001 an indicator 990:1001 ECAR; an indicator of glycolysis 984:1015 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 3 77 theme O-GlcNAcylation 665:679 arg1 impact 643:648 the impact 639:648 the impact of the HBP and O-GlcNAcylation on metabolic activity 639:701 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 13 78 theme types 2471:2475 arg1 GCs 2459:2461 GCs 2459:2461 GCs of both types of follicles 2459:2488 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 1 79 theme ovarian 155:161 arg1 follicles 163:171 ovarian follicles 155:171 ovarian follicles 155:171 Granulosa cells (GCs) of ovarian follicles prefer glucose as a metabolic substrate for growth and maturation. 36690170 6 80 theme antral 1325:1330 arg1 follicles 1332:1340 large antral follicles 1319:1340 large antral follicles 1319:1340 GCs from small antral follicles exhibited overall greater metabolic activity than GCs from large antral follicles as evidenced by increased ECAR and OCR. 36690170 3 81 theme HBP 657:659 arg1 impact 643:648 the impact 639:648 the impact of the HBP and O-GlcNAcylation on metabolic activity 639:701 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 13 82 theme follicles 2480:2488 arg1 types 2471:2475 both types 2466:2475 both types of follicles 2466:2488 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 14 83 theme follicles 2599:2607 arg1 GCs 2579:2581 GCs 2579:2581 GCs of small antral follicles 2579:2607 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 4 84 theme serum-free 802:811 arg1 medium 813:818 serum-free medium 802:818 serum-free medium 802:818 The GCs were initially cultured in serum-containing medium to confluency and then sub-cultured in serum-free medium in 96 well plates (n = 10 ovary pairs). 36690170 9 85 theme mitochondrial 1837:1849 arg1 test 1858:1861 the mitochondrial stress test 1833:1861 the mitochondrial stress test 1833:1861 Interestingly, inhibition of cellular respiration by 2-Deoxy-D-glucose impaired OCR only in GCs from small antral follicles, but exposure to the mitochondrial stress test had no effect. 36690170 14 86 theme small 2586:2590 arg1 follicles 2599:2607 small antral follicles 2586:2607 small antral follicles 2586:2607 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 10 87 theme glycolytic 2042:2051 arg1 metabolism 2053:2062 glycolytic metabolism 2042:2062 glycolytic metabolism 2042:2062 Conversely, in GCs from large antral follicles, oxidative metabolism was impaired by the mitochondrial stress test and was accompanied by a concomitant increase in glycolytic metabolism. 36690170 3 88 theme metabolic 684:692 arg1 activity 694:701 metabolic activity 684:701 metabolic activity 684:701 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 6 89 theme antral 1243:1248 arg1 follicles 1250:1258 small antral follicles 1237:1258 small antral follicles 1237:1258 GCs from small antral follicles exhibited overall greater metabolic activity than GCs from large antral follicles as evidenced by increased ECAR and OCR. 36690170 8 90 theme HBP 1647:1649 arg1 inhibition 1629:1638 inhibition 1629:1638 inhibition of the HBP and O-GlcNAcylation 1629:1669 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36690170 1 91 theme metabolic 193:201 arg1 glucose 180:186 glucose 180:186 glucose 180:186 Granulosa cells (GCs) of ovarian follicles prefer glucose as a metabolic substrate for growth and maturation. 36690170 1 91 theme metabolic 193:201 arg1 substrate 203:211 a metabolic substrate 191:211 a metabolic substrate for growth and maturation 191:237 Granulosa cells (GCs) of ovarian follicles prefer glucose as a metabolic substrate for growth and maturation. 36690170 3 92 from impact 643:648 arg1 activity 694:701 metabolic activity 684:701 metabolic activity 684:701 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 13 93 theme kinase 2422:2427 arg1 expression 2378:2387 the expression 2374:2387 the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles 2374:2488 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 12 94 theme antral 2312:2317 arg1 follicles 2319:2327 small antral follicles 2306:2327 small antral follicles 2306:2327 Inhibition of O-GlcNAcylation impaired the expression of hexokinase only in GCs of small antral follicles. 36690170 8 95 theme O-GlcNAcylation 1655:1669 arg1 inhibition 1629:1638 inhibition 1629:1638 inhibition of the HBP and O-GlcNAcylation 1629:1669 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36690170 10 96 from follicles 1915:1923 arg1 GCs 1893:1895 GCs 1893:1895 GCs from large antral follicles 1893:1923 Conversely, in GCs from large antral follicles, oxidative metabolism was impaired by the mitochondrial stress test and was accompanied by a concomitant increase in glycolytic metabolism. 36690170 5 97 theme glycolytic 1185:1194 arg1 tests 1221:1225 glycolytic and mitochondrial stress tests 1185:1225 glycolytic and mitochondrial stress tests 1185:1225 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 13 98 theme pyruvate 2433:2440 arg1 dehydrogenase 2442:2454 pyruvate dehydrogenase 2433:2454 pyruvate dehydrogenase 2433:2454 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 8 99 contain possessed 1576:1584 arg1 GCs 1543:1545 GCs 1543:1545 GCs from both types of follicles 1543:1574 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36690170 8 99 contain possessed 1576:1584 arg2 capacity 1608:1615 additional glycolytic capacity 1586:1615 additional glycolytic capacity 1586:1615 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36690170 3 100 theme study 566:570 arg1 aim 554:556 the aim 550:556 the aim of this study 550:570 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 1 101 theme Granulosa 130:138 arg1 GCs 147:149 GCs 147:149 GCs 147:149 Granulosa cells (GCs) of ovarian follicles prefer glucose as a metabolic substrate for growth and maturation. 36690170 1 101 theme Granulosa 130:138 arg1 cells 140:144 Granulosa cells 130:144 Granulosa cells (GCs) of ovarian follicles 130:171 Granulosa cells (GCs) of ovarian follicles prefer glucose as a metabolic substrate for growth and maturation. 36690170 4 102 theme ovary 846:850 arg1 pairs 852:856 n = 10 ovary pairs 839:856 n = 10 ovary pairs 839:856 The GCs were initially cultured in serum-containing medium to confluency and then sub-cultured in serum-free medium in 96 well plates (n = 10 ovary pairs). 36690170 4 102 theme ovary 846:850 arg1 plates 831:836 96 well plates 823:836 96 well plates (n = 10 ovary pairs) 823:857 The GCs were initially cultured in serum-containing medium to confluency and then sub-cultured in serum-free medium in 96 well plates (n = 10 ovary pairs). 36690170 14 103 theme O-GlcNAcylation 2721:2735 arg1 disruption 2695:2704 disruption 2695:2704 disruption of the HBP and O-GlcNAcylation 2695:2735 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 5 104 theme mitochondrial 1200:1212 arg1 tests 1221:1225 glycolytic and mitochondrial stress tests 1185:1225 glycolytic and mitochondrial stress tests 1185:1225 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 6 105 theme large 1319:1323 arg1 follicles 1332:1340 large antral follicles 1319:1340 large antral follicles 1319:1340 GCs from small antral follicles exhibited overall greater metabolic activity than GCs from large antral follicles as evidenced by increased ECAR and OCR. 36690170 14 106 theme HBP 2713:2715 arg1 disruption 2695:2704 disruption 2695:2704 disruption of the HBP and O-GlcNAcylation 2695:2735 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 10 107 theme large 1902:1906 arg1 follicles 1915:1923 large antral follicles 1902:1923 large antral follicles 1902:1923 Conversely, in GCs from large antral follicles, oxidative metabolism was impaired by the mitochondrial stress test and was accompanied by a concomitant increase in glycolytic metabolism. 36690170 0 108 theme glucose 84:90 arg1 metabolism 92:101 glucose metabolism 84:101 glucose metabolism in bovine granulosa cells 84:127 Evaluating the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells. 36690170 2 109 theme antral 465:470 arg1 follicles 472:480 both small (3-5 mm) and large (>8.5 mm) antral follicles 425:480 follicles 472:480 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 12 110 theme O-GlcNAcylation 2237:2251 arg1 Inhibition 2223:2232 Inhibition 2223:2232 Inhibition of O-GlcNAcylation 2223:2251 Inhibition of O-GlcNAcylation impaired the expression of hexokinase only in GCs of small antral follicles. 36690170 7 111 theme GCs 1467:1469 arg1 activity 1455:1462 the metabolic activity 1441:1462 the metabolic activity of GCs from either type of follicle 1441:1498 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 11 112 theme follicles 2184:2192 arg1 GCs 2164:2166 GCs 2164:2166 GCs of small antral follicles 2164:2192 Immunodetection of glycolytic enzymes revealed that phosphofructokinase expression is increased in GCs of small antral follicles compared to large follicles. 36690170 10 113 theme oxidative 1926:1934 arg1 metabolism 1936:1945 oxidative metabolism 1926:1945 oxidative metabolism 1926:1945 Conversely, in GCs from large antral follicles, oxidative metabolism was impaired by the mitochondrial stress test and was accompanied by a concomitant increase in glycolytic metabolism. 36690170 0 114 theme granulosa 113:121 arg1 cells 123:127 bovine granulosa cells 106:127 bovine granulosa cells 106:127 Evaluating the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells. 36690170 5 115 theme oxygen 1022:1027 arg1 OCR 1047:1049 OCR 1047:1049 OCR; an indicator of oxidative phosphorylation 1047:1092 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 5 115 theme oxygen 1022:1027 arg1 rate 1041:1044 oxygen consumption rate 1022:1044 oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs 1022:1104 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 11 116 theme small 2171:2175 arg1 follicles 2184:2192 small antral follicles 2171:2192 small antral follicles 2171:2192 Immunodetection of glycolytic enzymes revealed that phosphofructokinase expression is increased in GCs of small antral follicles compared to large follicles. 36690170 8 117 from types 1557:1561 arg1 GCs 1543:1545 GCs 1543:1545 GCs from both types of follicles 1543:1574 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36690170 6 118 theme greater 1278:1284 arg1 activity 1296:1303 overall greater metabolic activity 1270:1303 overall greater metabolic activity than GCs from large antral follicles 1270:1340 GCs from small antral follicles exhibited overall greater metabolic activity than GCs from large antral follicles as evidenced by increased ECAR and OCR. 36690170 13 119 theme lactate 2530:2536 arg1 dehydrogenase 2538:2550 lactate dehydrogenase 2530:2550 lactate dehydrogenase 2530:2550 Inhibition of O-GlcNAcylation also impaired the expression of phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase in GCs of both types of follicles, but had no effect on the expression of lactate dehydrogenase. 36690170 11 120 theme enzymes 2095:2101 arg1 Immunodetection 2065:2079 Immunodetection 2065:2079 Immunodetection of glycolytic enzymes 2065:2101 Immunodetection of glycolytic enzymes revealed that phosphofructokinase expression is increased in GCs of small antral follicles compared to large follicles. 36690170 5 121 theme tests 1221:1225 arg1 implementation 1167:1180 the implementation 1163:1180 the implementation of glycolytic and mitochondrial stress tests 1163:1225 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 6 122 theme increased 1358:1366 arg1 ECAR 1368:1371 ECAR 1368:1371 ECAR 1368:1371 GCs from small antral follicles exhibited overall greater metabolic activity than GCs from large antral follicles as evidenced by increased ECAR and OCR. 36690170 7 123 dep HBP 1400:1402 arg1 the 1396:1398 the 1396:1398 the 1396:1398 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 9 124 theme respiration 1730:1740 arg1 inhibition 1707:1716 inhibition 1707:1716 inhibition of cellular respiration by 2-Deoxy-D-glucose 1707:1761 Interestingly, inhibition of cellular respiration by 2-Deoxy-D-glucose impaired OCR only in GCs from small antral follicles, but exposure to the mitochondrial stress test had no effect. 36690170 3 125 theme glucose 592:598 arg1 metabolism 600:609 glucose metabolism 592:609 glucose metabolism in bovine GCs 592:623 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 0 126 theme hexosamine 29:38 arg1 pathway 53:59 the hexosamine biosynthesis pathway 25:59 the hexosamine biosynthesis pathway 25:59 Evaluating the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells. 36690170 6 127 from follicles 1250:1258 arg1 GCs 1228:1230 GCs 1228:1230 GCs from small antral follicles 1228:1258 GCs from small antral follicles exhibited overall greater metabolic activity than GCs from large antral follicles as evidenced by increased ECAR and OCR. 36690170 5 128 theme 24 h. 944:948 arg1 ECAR 984:987 ECAR 984:987 ECAR; an indicator of glycolysis 984:1015 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 5 128 theme 24 h. 944:948 arg1 rate 978:981 24 h. Extracellular acidification rate 944:981 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) 944:1016 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 8 129 theme follicles 1566:1574 arg1 types 1557:1561 both types 1552:1561 both types of follicles 1552:1574 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36690170 14 130 theme antral 2673:2678 arg1 follicles 2680:2688 large antral follicles 2667:2688 large antral follicles 2667:2688 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 2 131 theme >8.5 mm 456:462 arg1 follicles 472:480 both small (3-5 mm) and large (>8.5 mm) antral follicles 425:480 follicles 472:480 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 14 132 contain possess 2609:2615 arg1 GCs 2579:2581 GCs 2579:2581 GCs of small antral follicles 2579:2607 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 14 132 contain possess 2609:2615 arg2 capacity 2644:2651 greater aerobic glycolytic capacity 2617:2651 greater aerobic glycolytic capacity than GCs from large antral follicles 2617:2688 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 14 133 dep HBP 2713:2715 arg1 the 2709:2711 the 2709:2711 the 2709:2711 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 2 134 theme GCs 418:420 arg1 proliferation 394:406 proliferation 394:406 proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles 394:480 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 0 135 theme pathway 53:59 arg1 impact 15:20 the impact 11:20 the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells 11:127 Evaluating the impact of the hexosamine biosynthesis pathway and O-GlcNAcylation on glucose metabolism in bovine granulosa cells. 36690170 3 136 dep HBP 657:659 arg1 the 653:655 the 653:655 the 653:655 Knowing that 2-5% of all glucose in cells is utilized via the HBP, the aim of this study was to characterize glucose metabolism in bovine GCs and determine the impact of the HBP and O-GlcNAcylation on metabolic activity. 36690170 7 137 theme metabolic 1445:1453 arg1 activity 1455:1462 the metabolic activity 1441:1462 the metabolic activity of GCs from either type of follicle 1441:1498 Inhibition of the HBP and O-GlcNAcylation had no effect on the metabolic activity of GCs from either type of follicle. 36690170 5 138 theme acidification 964:976 arg1 ECAR 984:987 ECAR 984:987 ECAR; an indicator of glycolysis 984:1015 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 5 138 theme acidification 964:976 arg1 rate 978:981 24 h. Extracellular acidification rate 944:981 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) 944:1016 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 2 139 theme large 449:453 arg1 follicles 472:480 both small (3-5 mm) and large (>8.5 mm) antral follicles 425:480 follicles 472:480 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 14 140 from impact 2754:2759 arg1 activity 2774:2781 metabolic activity 2764:2781 metabolic activity 2764:2781 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 2 141 theme O-linked 328:335 arg1 O-GlcNAcylation 364:378 O-GlcNAcylation 364:378 O-GlcNAcylation 364:378 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 2 141 theme O-linked 328:335 arg1 N-acetylglucosaminylation 337:361 O-linked N-acetylglucosaminylation 328:361 O-linked N-acetylglucosaminylation (O-GlcNAcylation) 328:379 Disruption of glucose utilization via the hexosamine biosynthesis pathway (HBP) impairs O-linked N-acetylglucosaminylation (O-GlcNAcylation) and inhibits proliferation of bovine GCs of both small (3-5 mm) and large (>8.5 mm) antral follicles. 36690170 5 142 theme phosphorylation 1078:1092 arg1 indicator 1055:1063 an indicator 1052:1063 OCR; an indicator of oxidative phosphorylation 1047:1092 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 5 143 theme HBP 916:918 arg1 inhibitors 898:907 inhibitors 898:907 inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs 898:1104 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 10 144 theme mitochondrial 1967:1979 arg1 test 1988:1991 the mitochondrial stress test 1963:1991 the mitochondrial stress test 1963:1991 Conversely, in GCs from large antral follicles, oxidative metabolism was impaired by the mitochondrial stress test and was accompanied by a concomitant increase in glycolytic metabolism. 36690170 8 145 theme stress 1516:1521 arg1 test 1523:1526 The glycolytic stress test 1501:1526 The glycolytic stress test 1501:1526 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36690170 5 146 theme xFe96 1137:1141 arg1 Analyzer 1143:1150 a Seahorse xFe96 Analyzer 1126:1150 a Seahorse xFe96 Analyzer 1126:1150 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 5 147 theme O-GlcNAcylation 924:938 arg1 inhibitors 898:907 inhibitors 898:907 inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs 898:1104 The cells were exposed to vehicle and inhibitors of the HBP and O-GlcNAcylation for 24 h. Extracellular acidification rate (ECAR; an indicator of glycolysis) and oxygen consumption rate (OCR; an indicator of oxidative phosphorylation) of the GCs were measured using a Seahorse xFe96 Analyzer, including the implementation of glycolytic and mitochondrial stress tests. 36690170 14 148 theme glycolytic 2633:2642 arg1 capacity 2644:2651 greater aerobic glycolytic capacity 2617:2651 greater aerobic glycolytic capacity than GCs from large antral follicles 2617:2688 The results indicate that GCs of small antral follicles possess greater aerobic glycolytic capacity than GCs from large antral follicles; but disruption of the HBP and O-GlcNAcylation has little to no impact on metabolic activity. 36690170 4 149 theme serum-containing 739:754 arg1 medium 756:761 serum-containing medium 739:761 serum-containing medium 739:761 The GCs were initially cultured in serum-containing medium to confluency and then sub-cultured in serum-free medium in 96 well plates (n = 10 ovary pairs). 36690170 8 150 theme glycolytic 1597:1606 arg1 capacity 1608:1615 additional glycolytic capacity 1586:1615 additional glycolytic capacity 1586:1615 The glycolytic stress test indicated that GCs from both types of follicles possessed additional glycolytic capacity; but again, inhibition of the HBP and O-GlcNAcylation did not affect this. 36642184 4 0 theme protein 603:609 arg1 kinase 611:616 mitogen-activated protein kinase 585:616 The mitogen-activated protein kinase (MAPK) pathway 581:631 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 4 0 theme protein 603:609 arg1 MAPK 619:622 MAPK 619:622 MAPK 619:622 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 7 1 theme click 1146:1150 arg1 chemistry 1153:1161 alkyne-azide 'click' chemistry 1132:1161 alkyne-azide 'click' chemistry 1132:1161 Using metabolic labeling of glycans coupled with alkyne-azide 'click' chemistry we found that Erk1/2 and p38 are O-GlcNAcylated. 36642184 10 2 theme maladaptive 1766:1776 arg1 factors 1790:1796 maladaptive natriuretic factors 1766:1796 maladaptive natriuretic factors Anp and Bnp 1766:1808 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 2 theme maladaptive 1766:1776 arg1 Bnp 1806:1808 Bnp 1806:1808 Bnp 1806:1808 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 2 theme maladaptive 1766:1776 arg1 Anp 1798:1800 Anp 1798:1800 Anp 1798:1800 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 1 3 theme conserved 261:269 arg1 O-GlcNAcase 310:320 O-GlcNAcase 310:320 O-GlcNAcase (OGA) 310:326 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 3 theme conserved 261:269 arg1 Transferase 288:298 O-GlcNAc Transferase 279:298 O-GlcNAc Transferase (OGT) 279:304 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 3 theme conserved 261:269 arg1 enzymes 271:277 the conserved enzymes 257:277 the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA) 257:326 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 7 4 theme alkyne-azide 1132:1143 arg1 chemistry 1153:1161 alkyne-azide 'click' chemistry 1132:1161 alkyne-azide 'click' chemistry 1132:1161 Using metabolic labeling of glycans coupled with alkyne-azide 'click' chemistry we found that Erk1/2 and p38 are O-GlcNAcylated. 36642184 11 5 theme p38 1928:1930 arg1 activity 1905:1912 a balanced activity 1894:1912 a balanced activity of Erk1/2 and p38 MAPKs 1894:1936 Collectively, these studies highlight new roles for O-GlcNAcylation in maintaining a balanced activity of Erk1/2 and p38 MAPKs during hypertrophic growth responses in cardiomyocytes. 36642184 1 6 theme O-GlcNAc 279:286 arg1 OGT 301:303 OGT 301:303 OGT 301:303 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 6 theme O-GlcNAc 279:286 arg1 Transferase 288:298 O-GlcNAc Transferase 279:298 O-GlcNAc Transferase (OGT) 279:304 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 6 theme O-GlcNAc 279:286 arg1 enzymes 271:277 the conserved enzymes 257:277 the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA) 257:326 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 2 7 theme stress 378:383 arg1 responses 385:393 homeostatic and stress responses 362:393 responses 385:393 O-GlcNAc cycling is important in homeostatic and stress responses and its perturbation sensitizes the heart to ischemic and other injuries. 36642184 10 8 theme hypertrophic 1607:1618 arg1 response 1620:1627 a blunted hypertrophic response 1597:1627 a blunted hypertrophic response to phenylephrine 1597:1644 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 5 9 theme Erk 829:831 arg1 kinases 833:839 Erk kinases 829:839 Erk kinases 829:839 The developmental or adaptive arm of MAPK signaling is primarily mediated by Erk kinases while the pathophysiologic arm is mediated by p38 and Jnk kinases. 36642184 7 10 dep found 1166:1170 arg1 Using 1083:1087 Using 1083:1087 Using metabolic labeling of glycans coupled with alkyne-azide 'click' chemistry 1083:1161 Using metabolic labeling of glycans coupled with alkyne-azide 'click' chemistry we found that Erk1/2 and p38 are O-GlcNAcylated. 36642184 1 11 theme intracellular 194:206 arg1 proteins 208:215 intracellular proteins 194:215 intracellular proteins 194:215 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 4 12 theme central 638:644 arg1 cascade 656:662 a central signaling cascade 636:662 a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart 636:749 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 4 12 theme central 638:644 arg1 pathway 625:631 The mitogen-activated protein kinase (MAPK) pathway 581:631 The mitogen-activated protein kinase (MAPK) pathway 581:631 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 11 13 theme new 1849:1851 arg1 roles 1853:1857 new roles 1849:1857 new roles for O-GlcNAcylation 1849:1877 Collectively, these studies highlight new roles for O-GlcNAcylation in maintaining a balanced activity of Erk1/2 and p38 MAPKs during hypertrophic growth responses in cardiomyocytes. 36642184 7 14 theme metabolic 1089:1097 arg1 labeling 1099:1106 metabolic labeling 1089:1106 metabolic labeling of glycans coupled with alkyne-azide 'click' chemistry 1089:1161 Using metabolic labeling of glycans coupled with alkyne-azide 'click' chemistry we found that Erk1/2 and p38 are O-GlcNAcylated. 36642184 5 15 theme pathophysiologic 851:866 arg1 arm 868:870 the pathophysiologic arm 847:870 the pathophysiologic arm 847:870 The developmental or adaptive arm of MAPK signaling is primarily mediated by Erk kinases while the pathophysiologic arm is mediated by p38 and Jnk kinases. 36642184 9 16 theme Erk1/2 1512:1517 arg1 phosphorylation 1493:1507 the phenylephrine-induced phosphorylation 1467:1507 the phenylephrine-induced phosphorylation of Erk1/2 1467:1517 Additionally, OGT inhibition blocks the phenylephrine-induced phosphorylation of Erk1/2. 36642184 8 17 theme p38 1241:1243 arg1 regulation 1227:1236 the regulation 1223:1236 the regulation of p38 by O-GlcNAcylation 1223:1262 Supporting the regulation of p38 by O-GlcNAcylation, the OGT inhibitor, OSMI-1, triggers the phosphorylation of p38, an event that involves the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1. 36642184 6 18 theme MAPK 957:960 arg1 signaling 962:970 MAPK signaling 957:970 MAPK signaling in cardiac myocytes 957:990 Here, we examine whether O-GlcNAcylation affects MAPK signaling in cardiac myocytes, focusing on Erk1/2 and p38 in basal and hypertrophic conditions induced by phenylephrine. 36642184 10 19 theme expression 1670:1679 arg1 expression 1752:1761 increased expression 1742:1761 increased expression of maladaptive natriuretic factors Anp and Bnp 1742:1808 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 19 theme expression 1670:1679 arg1 response 1620:1627 a blunted hypertrophic response 1597:1627 a blunted hypertrophic response to phenylephrine 1597:1644 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 19 theme expression 1670:1679 arg1 downregulation 1647:1660 downregulation 1647:1660 downregulation of cTnT expression (encoding a key component of the contractile apparatus) 1647:1735 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 1 20 theme N-Acetylglucosamine 132:150 arg1 cycling 112:118 The dynamic cycling 100:118 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, 100:240 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 10 21 with Consistent 1520:1529 arg1 signaling 1551:1559 perturbed MAPK signaling 1536:1559 perturbed MAPK signaling 1536:1559 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 6 22 theme basal 1023:1027 arg1 conditions 1046:1055 basal and hypertrophic conditions 1023:1055 basal and hypertrophic conditions induced by phenylephrine 1023:1080 Here, we examine whether O-GlcNAcylation affects MAPK signaling in cardiac myocytes, focusing on Erk1/2 and p38 in basal and hypertrophic conditions induced by phenylephrine. 36642184 11 23 from responses 1965:1973 arg1 cardiomyocytes 1978:1991 cardiomyocytes 1978:1991 cardiomyocytes 1978:1991 Collectively, these studies highlight new roles for O-GlcNAcylation in maintaining a balanced activity of Erk1/2 and p38 MAPKs during hypertrophic growth responses in cardiomyocytes. 36642184 8 24 theme p38 1324:1326 arg1 phosphorylation 1305:1319 the phosphorylation 1301:1319 the phosphorylation of p38, an event that involves the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1 1301:1428 Supporting the regulation of p38 by O-GlcNAcylation, the OGT inhibitor, OSMI-1, triggers the phosphorylation of p38, an event that involves the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1. 36642184 4 25 theme pathological 715:726 arg1 responses 728:736 developmental, physiological, and pathological responses 681:736 developmental, physiological, and pathological responses 681:736 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 5 26 theme MAPK 789:792 arg1 signaling 794:802 MAPK signaling 789:802 MAPK signaling 789:802 The developmental or adaptive arm of MAPK signaling is primarily mediated by Erk kinases while the pathophysiologic arm is mediated by p38 and Jnk kinases. 36642184 10 27 contain have 1592:1595 arg1 cardiomyocytes 1577:1590 OSMI-1-treated cardiomyocytes 1562:1590 OSMI-1-treated cardiomyocytes 1562:1590 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 27 contain have 1592:1595 arg2 response 1620:1627 a blunted hypertrophic response 1597:1627 a blunted hypertrophic response to phenylephrine 1597:1644 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 27 contain have 1592:1595 arg2 downregulation 1647:1660 downregulation 1647:1660 downregulation of cTnT expression (encoding a key component of the contractile apparatus) 1647:1735 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 27 contain have 1592:1595 arg2 expression 1752:1761 increased expression 1742:1761 increased expression of maladaptive natriuretic factors Anp and Bnp 1742:1808 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 0 28 theme Erk1/2 43:48 arg1 signaling 50:58 p38 and Erk1/2 signaling 35:58 p38 and Erk1/2 signaling 35:58 Inhibiting O-GlcNAcylation impacts p38 and Erk1/2 signaling and perturbs cardiomyocyte hypertrophy. 36642184 0 29 theme cardiomyocyte 73:85 arg1 hypertrophy 87:97 cardiomyocyte hypertrophy 73:97 cardiomyocyte hypertrophy 73:97 Inhibiting O-GlcNAcylation impacts p38 and Erk1/2 signaling and perturbs cardiomyocyte hypertrophy. 36642184 8 30 theme signaling 1373:1381 arg1 axis 1383:1386 the NOX2-Ask1-MKK3/6 signaling axis 1352:1386 the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1 1352:1428 Supporting the regulation of p38 by O-GlcNAcylation, the OGT inhibitor, OSMI-1, triggers the phosphorylation of p38, an event that involves the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1. 36642184 11 31 theme growth 1958:1963 arg1 responses 1965:1973 hypertrophic growth responses 1945:1973 hypertrophic growth responses in cardiomyocytes 1945:1991 Collectively, these studies highlight new roles for O-GlcNAcylation in maintaining a balanced activity of Erk1/2 and p38 MAPKs during hypertrophic growth responses in cardiomyocytes. 36642184 0 32 theme Inhibiting 0:9 arg1 O-GlcNAcylation 11:25 Inhibiting O-GlcNAcylation 0:25 Inhibiting O-GlcNAcylation 0:25 Inhibiting O-GlcNAcylation impacts p38 and Erk1/2 signaling and perturbs cardiomyocyte hypertrophy. 36642184 1 33 theme dynamic 104:110 arg1 cycling 112:118 The dynamic cycling 100:118 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, 100:240 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 10 34 theme perturbed 1536:1544 arg1 signaling 1551:1559 perturbed MAPK signaling 1536:1559 perturbed MAPK signaling 1536:1559 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 5 35 dep p38 887:889 arg1 kinases 899:905 kinases 899:905 kinases 899:905 The developmental or adaptive arm of MAPK signaling is primarily mediated by Erk kinases while the pathophysiologic arm is mediated by p38 and Jnk kinases. 36642184 10 36 theme apparatus 1726:1734 arg1 component 1697:1705 a key component 1691:1705 a key component of the contractile apparatus 1691:1734 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 9 37 theme OGT 1445:1447 arg1 inhibition 1449:1458 OGT inhibition 1445:1458 OGT inhibition 1445:1458 Additionally, OGT inhibition blocks the phenylephrine-induced phosphorylation of Erk1/2. 36642184 6 38 theme hypertrophic 1033:1044 arg1 conditions 1046:1055 basal and hypertrophic conditions 1023:1055 basal and hypertrophic conditions induced by phenylephrine 1023:1080 Here, we examine whether O-GlcNAcylation affects MAPK signaling in cardiac myocytes, focusing on Erk1/2 and p38 in basal and hypertrophic conditions induced by phenylephrine. 36642184 10 39 theme OSMI-1-treated 1562:1575 arg1 cardiomyocytes 1577:1590 OSMI-1-treated cardiomyocytes 1562:1590 OSMI-1-treated cardiomyocytes 1562:1590 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 8 40 theme activator 1415:1423 arg1 Tab1 1425:1428 the non-canonical activator Tab1 1397:1428 the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1 1352:1428 Supporting the regulation of p38 by O-GlcNAcylation, the OGT inhibitor, OSMI-1, triggers the phosphorylation of p38, an event that involves the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1. 36642184 11 41 theme Erk1/2 1917:1922 arg1 activity 1905:1912 a balanced activity 1894:1912 a balanced activity of Erk1/2 and p38 MAPKs 1894:1936 Collectively, these studies highlight new roles for O-GlcNAcylation in maintaining a balanced activity of Erk1/2 and p38 MAPKs during hypertrophic growth responses in cardiomyocytes. 36642184 6 42 from signaling 962:970 arg1 myocytes 983:990 cardiac myocytes 975:990 cardiac myocytes 975:990 Here, we examine whether O-GlcNAcylation affects MAPK signaling in cardiac myocytes, focusing on Erk1/2 and p38 in basal and hypertrophic conditions induced by phenylephrine. 36642184 10 43 theme increased 1742:1750 arg1 expression 1752:1761 increased expression 1742:1761 increased expression of maladaptive natriuretic factors Anp and Bnp 1742:1808 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 44 theme blunted 1599:1605 arg1 response 1620:1627 a blunted hypertrophic response 1597:1627 a blunted hypertrophic response to phenylephrine 1597:1644 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 2 45 theme homeostatic 362:372 arg1 responses 385:393 homeostatic and stress responses 362:393 responses 385:393 O-GlcNAc cycling is important in homeostatic and stress responses and its perturbation sensitizes the heart to ischemic and other injuries. 36642184 3 46 theme molecular 505:513 arg1 pathways 515:522 many molecular pathways 500:522 many molecular pathways impacted by O-GlcNAcylation in the heart 500:563 Despite considerable progress, many molecular pathways impacted by O-GlcNAcylation in the heart remain unclear. 36642184 4 47 theme mitogen-activated 585:601 arg1 kinase 611:616 mitogen-activated protein kinase 585:616 The mitogen-activated protein kinase (MAPK) pathway 581:631 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 4 47 theme mitogen-activated 585:601 arg1 MAPK 619:622 MAPK 619:622 MAPK 619:622 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 4 48 theme kinase 611:616 arg1 cascade 656:662 a central signaling cascade 636:662 a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart 636:749 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 4 48 theme kinase 611:616 arg1 pathway 625:631 The mitogen-activated protein kinase (MAPK) pathway 581:631 The mitogen-activated protein kinase (MAPK) pathway 581:631 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 7 49 theme glycans 1111:1117 arg1 labeling 1099:1106 metabolic labeling 1089:1106 metabolic labeling of glycans coupled with alkyne-azide 'click' chemistry 1089:1161 Using metabolic labeling of glycans coupled with alkyne-azide 'click' chemistry we found that Erk1/2 and p38 are O-GlcNAcylated. 36642184 1 50 theme Ser/Thr 174:180 arg1 residues 182:189 Ser/Thr residues 174:189 Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, 174:240 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 50 theme Ser/Thr 174:180 arg1 proteins 208:215 intracellular proteins 194:215 intracellular proteins 194:215 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 2 51 from important 349:357 arg1 responses 385:393 homeostatic and stress responses 362:393 responses 385:393 O-GlcNAc cycling is important in homeostatic and stress responses and its perturbation sensitizes the heart to ischemic and other injuries. 36642184 10 52 theme cTnT 1665:1668 arg1 expression 1670:1679 cTnT expression 1665:1679 cTnT expression (encoding a key component of the contractile apparatus) 1665:1735 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 4 53 theme developmental 681:693 arg1 responses 728:736 developmental, physiological, and pathological responses 681:736 developmental, physiological, and pathological responses 681:736 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 1 54 dep residues 182:189 arg1 off 170:172 off 170:172 off 170:172 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 9 55 theme phenylephrine-induced 1471:1491 arg1 phosphorylation 1493:1507 the phenylephrine-induced phosphorylation 1467:1507 the phenylephrine-induced phosphorylation of Erk1/2 1467:1517 Additionally, OGT inhibition blocks the phenylephrine-induced phosphorylation of Erk1/2. 36642184 6 56 theme cardiac 975:981 arg1 myocytes 983:990 cardiac myocytes 975:990 cardiac myocytes 975:990 Here, we examine whether O-GlcNAcylation affects MAPK signaling in cardiac myocytes, focusing on Erk1/2 and p38 in basal and hypertrophic conditions induced by phenylephrine. 36642184 8 57 theme OGT 1269:1271 arg1 inhibitor 1273:1281 the OGT inhibitor 1265:1281 the OGT inhibitor 1265:1281 Supporting the regulation of p38 by O-GlcNAcylation, the OGT inhibitor, OSMI-1, triggers the phosphorylation of p38, an event that involves the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1. 36642184 8 57 theme OGT 1269:1271 arg1 OSMI-1 1284:1289 OSMI-1 1284:1289 OSMI-1 1284:1289 Supporting the regulation of p38 by O-GlcNAcylation, the OGT inhibitor, OSMI-1, triggers the phosphorylation of p38, an event that involves the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1. 36642184 2 58 theme O-GlcNAc 329:336 arg1 cycling 338:344 O-GlcNAc cycling 329:344 O-GlcNAc cycling 329:344 O-GlcNAc cycling is important in homeostatic and stress responses and its perturbation sensitizes the heart to ischemic and other injuries. 36642184 4 59 theme signaling 646:654 arg1 cascade 656:662 a central signaling cascade 636:662 a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart 636:749 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 4 59 theme signaling 646:654 arg1 pathway 625:631 The mitogen-activated protein kinase (MAPK) pathway 581:631 The mitogen-activated protein kinase (MAPK) pathway 581:631 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 11 60 theme balanced 1896:1903 arg1 activity 1905:1912 a balanced activity 1894:1912 a balanced activity of Erk1/2 and p38 MAPKs 1894:1936 Collectively, these studies highlight new roles for O-GlcNAcylation in maintaining a balanced activity of Erk1/2 and p38 MAPKs during hypertrophic growth responses in cardiomyocytes. 36642184 1 61 link O-linked 123:130 arg1 O-GlcNAc 153:160 O-GlcNAc 153:160 O-GlcNAc 153:160 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 61 link O-linked 123:130 arg1 N-Acetylglucosamine 132:150 O-linked N-Acetylglucosamine 123:150 O-linked N-Acetylglucosamine (O-GlcNAc) 123:161 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 62 theme O-linked 123:130 arg1 O-GlcNAc 153:160 O-GlcNAc 153:160 O-GlcNAc 153:160 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 62 theme O-linked 123:130 arg1 N-Acetylglucosamine 132:150 O-linked N-Acetylglucosamine 123:150 O-linked N-Acetylglucosamine (O-GlcNAc) 123:161 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 63 dep enzymes 271:277 arg1 OGT 301:303 OGT 301:303 OGT 301:303 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 63 dep enzymes 271:277 arg1 O-GlcNAcase 310:320 O-GlcNAcase 310:320 O-GlcNAcase (OGA) 310:326 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 63 dep enzymes 271:277 arg1 Transferase 288:298 O-GlcNAc Transferase 279:298 O-GlcNAc Transferase (OGT) 279:304 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 63 dep enzymes 271:277 arg1 enzymes 271:277 the conserved enzymes 257:277 the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA) 257:326 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 63 dep enzymes 271:277 arg1 OGA 323:325 OGA 323:325 OGA 323:325 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 3 64 theme considerable 477:488 arg1 progress 490:497 considerable progress 477:497 considerable progress 477:497 Despite considerable progress, many molecular pathways impacted by O-GlcNAcylation in the heart remain unclear. 36642184 5 65 theme adaptive 773:780 arg1 arm 782:784 The developmental or adaptive arm 752:784 The developmental or adaptive arm of MAPK signaling 752:802 The developmental or adaptive arm of MAPK signaling is primarily mediated by Erk kinases while the pathophysiologic arm is mediated by p38 and Jnk kinases. 36642184 5 65 theme adaptive 773:780 arg1 signaling 794:802 MAPK signaling 789:802 MAPK signaling 789:802 The developmental or adaptive arm of MAPK signaling is primarily mediated by Erk kinases while the pathophysiologic arm is mediated by p38 and Jnk kinases. 36642184 1 66 theme proteins 208:215 arg1 residues 182:189 Ser/Thr residues 174:189 Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, 174:240 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 1 66 theme proteins 208:215 arg1 proteins 208:215 intracellular proteins 194:215 intracellular proteins 194:215 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 4 67 theme physiological 696:708 arg1 responses 728:736 developmental, physiological, and pathological responses 681:736 developmental, physiological, and pathological responses 681:736 The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that coordinates developmental, physiological, and pathological responses in the heart. 36642184 6 68 from p38 1016:1018 arg1 conditions 1046:1055 basal and hypertrophic conditions 1023:1055 basal and hypertrophic conditions induced by phenylephrine 1023:1080 Here, we examine whether O-GlcNAcylation affects MAPK signaling in cardiac myocytes, focusing on Erk1/2 and p38 in basal and hypertrophic conditions induced by phenylephrine. 36642184 5 69 theme developmental 756:768 arg1 arm 782:784 The developmental or adaptive arm 752:784 The developmental or adaptive arm of MAPK signaling 752:802 The developmental or adaptive arm of MAPK signaling is primarily mediated by Erk kinases while the pathophysiologic arm is mediated by p38 and Jnk kinases. 36642184 5 69 theme developmental 756:768 arg1 signaling 794:802 MAPK signaling 789:802 MAPK signaling 789:802 The developmental or adaptive arm of MAPK signaling is primarily mediated by Erk kinases while the pathophysiologic arm is mediated by p38 and Jnk kinases. 36642184 11 70 dep Erk1/2 1917:1922 arg1 MAPKs 1932:1936 MAPKs 1932:1936 MAPKs 1932:1936 Collectively, these studies highlight new roles for O-GlcNAcylation in maintaining a balanced activity of Erk1/2 and p38 MAPKs during hypertrophic growth responses in cardiomyocytes. 36642184 10 71 dep factors 1790:1796 arg1 factors 1790:1796 maladaptive natriuretic factors 1766:1796 maladaptive natriuretic factors Anp and Bnp 1766:1808 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 71 dep factors 1790:1796 arg1 Bnp 1806:1808 Bnp 1806:1808 Bnp 1806:1808 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 71 dep factors 1790:1796 arg1 Anp 1798:1800 Anp 1798:1800 Anp 1798:1800 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 2 72 theme ischemic 440:447 arg1 injuries 459:466 ischemic and other injuries 440:466 ischemic and other injuries 440:466 O-GlcNAc cycling is important in homeostatic and stress responses and its perturbation sensitizes the heart to ischemic and other injuries. 36642184 6 73 from Erk1/2 1005:1010 arg1 conditions 1046:1055 basal and hypertrophic conditions 1023:1055 basal and hypertrophic conditions induced by phenylephrine 1023:1080 Here, we examine whether O-GlcNAcylation affects MAPK signaling in cardiac myocytes, focusing on Erk1/2 and p38 in basal and hypertrophic conditions induced by phenylephrine. 36642184 8 74 theme NOX2-Ask1-MKK3/6 1356:1371 arg1 axis 1383:1386 the NOX2-Ask1-MKK3/6 signaling axis 1352:1386 the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1 1352:1428 Supporting the regulation of p38 by O-GlcNAcylation, the OGT inhibitor, OSMI-1, triggers the phosphorylation of p38, an event that involves the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1. 36642184 10 75 theme key 1693:1695 arg1 component 1697:1705 a key component 1691:1705 a key component of the contractile apparatus 1691:1734 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 0 76 theme p38 35:37 arg1 signaling 50:58 p38 and Erk1/2 signaling 35:58 p38 and Erk1/2 signaling 35:58 Inhibiting O-GlcNAcylation impacts p38 and Erk1/2 signaling and perturbs cardiomyocyte hypertrophy. 36642184 5 77 theme signaling 794:802 arg1 arm 782:784 The developmental or adaptive arm 752:784 The developmental or adaptive arm of MAPK signaling 752:802 The developmental or adaptive arm of MAPK signaling is primarily mediated by Erk kinases while the pathophysiologic arm is mediated by p38 and Jnk kinases. 36642184 5 77 theme signaling 794:802 arg1 signaling 794:802 MAPK signaling 789:802 MAPK signaling 789:802 The developmental or adaptive arm of MAPK signaling is primarily mediated by Erk kinases while the pathophysiologic arm is mediated by p38 and Jnk kinases. 36642184 10 78 theme contractile 1714:1724 arg1 apparatus 1726:1734 the contractile apparatus 1710:1734 the contractile apparatus 1710:1734 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 2 79 theme other 453:457 arg1 injuries 459:466 ischemic and other injuries 440:466 ischemic and other injuries 440:466 O-GlcNAc cycling is important in homeostatic and stress responses and its perturbation sensitizes the heart to ischemic and other injuries. 36642184 8 80 theme non-canonical 1401:1413 arg1 Tab1 1425:1428 the non-canonical activator Tab1 1397:1428 the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1 1352:1428 Supporting the regulation of p38 by O-GlcNAcylation, the OGT inhibitor, OSMI-1, triggers the phosphorylation of p38, an event that involves the NOX2-Ask1-MKK3/6 signaling axis but also the non-canonical activator Tab1. 36642184 3 81 theme many 500:503 arg1 pathways 515:522 many molecular pathways 500:522 many molecular pathways impacted by O-GlcNAcylation in the heart 500:563 Despite considerable progress, many molecular pathways impacted by O-GlcNAcylation in the heart remain unclear. 36642184 1 82 from cycling 112:118 arg1 and 166:168 and 166:168 and 166:168 The dynamic cycling of O-linked N-Acetylglucosamine (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). 36642184 2 83 from responses 385:393 arg1 important 349:357 important 349:357 important 349:357 O-GlcNAc cycling is important in homeostatic and stress responses and its perturbation sensitizes the heart to ischemic and other injuries. 36642184 10 84 theme MAPK 1546:1549 arg1 signaling 1551:1559 perturbed MAPK signaling 1536:1559 perturbed MAPK signaling 1536:1559 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 85 theme factors 1790:1796 arg1 expression 1752:1761 increased expression 1742:1761 increased expression of maladaptive natriuretic factors Anp and Bnp 1742:1808 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 85 theme factors 1790:1796 arg1 response 1620:1627 a blunted hypertrophic response 1597:1627 a blunted hypertrophic response to phenylephrine 1597:1644 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 85 theme factors 1790:1796 arg1 downregulation 1647:1660 downregulation 1647:1660 downregulation of cTnT expression (encoding a key component of the contractile apparatus) 1647:1735 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 86 theme natriuretic 1778:1788 arg1 factors 1790:1796 maladaptive natriuretic factors 1766:1796 maladaptive natriuretic factors Anp and Bnp 1766:1808 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 86 theme natriuretic 1778:1788 arg1 Bnp 1806:1808 Bnp 1806:1808 Bnp 1806:1808 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 10 86 theme natriuretic 1778:1788 arg1 Anp 1798:1800 Anp 1798:1800 Anp 1798:1800 Consistent with perturbed MAPK signaling, OSMI-1-treated cardiomyocytes have a blunted hypertrophic response to phenylephrine, downregulation of cTnT expression (encoding a key component of the contractile apparatus), and increased expression of maladaptive natriuretic factors Anp and Bnp. 36642184 11 87 theme hypertrophic 1945:1956 arg1 responses 1965:1973 hypertrophic growth responses 1945:1973 hypertrophic growth responses in cardiomyocytes 1945:1991 Collectively, these studies highlight new roles for O-GlcNAcylation in maintaining a balanced activity of Erk1/2 and p38 MAPKs during hypertrophic growth responses in cardiomyocytes. 36637425 7 0 theme mass 1206:1209 arg1 analysis 1225:1232 mass spectrometric analysis 1206:1232 mass spectrometric analysis 1206:1232 Using a truncated Cnm variant containing only two threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. 36637425 11 1 from importance 1769:1778 arg1 mutans 1848:1853 S. mutans 1845:1853 S. mutans 1845:1853 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 4 2 theme region 703:708 arg1 modification 651:662 post-translational modification 632:662 post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2 632:804 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 4 2 theme region 703:708 arg1 PTM 665:667 PTM 665:667 PTM 665:667 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 5 3 from virulence 959:967 arg1 model 1009:1013 the Galleria mellonella invertebrate model 972:1013 the Galleria mellonella invertebrate model 972:1013 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 9 4 theme S. 1428:1429 arg1 GalE 1450:1453 the other S. mutans 4-epimerase GalE 1418:1453 the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis 1418:1517 Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis, demonstrated that GalE is a UDP-Glc-4-epimerase while PgfE is a GlcNAc-4-epimerase. 36637425 0 5 theme protein 70:76 arg1 glycosylation 78:90 protein glycosylation 70:90 protein glycosylation 70:90 Involvement of the Streptococcus mutans PgfE and GalE 4-epimerases in protein glycosylation, carbon metabolism and cell division. 36637425 7 6 with glycosylation 1253:1265 arg1 HexNAc2 1272:1278 HexNAc2 1272:1278 HexNAc2 1272:1278 Using a truncated Cnm variant containing only two threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. 36637425 5 7 theme collagen 866:873 arg1 binding 875:881 decreased collagen binding 856:881 decreased collagen binding 856:881 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 1 8 theme key 156:158 arg1 pathogen 160:167 a key pathogen 154:167 a key pathogen associated with dental caries 154:197 Streptococcus mutans is a key pathogen associated with dental caries and is often implicated in infective endocarditis. 36637425 1 8 theme key 156:158 arg1 mutans 144:149 Streptococcus mutans 130:149 Streptococcus mutans 130:149 Streptococcus mutans is a key pathogen associated with dental caries and is often implicated in infective endocarditis. 36637425 9 9 theme mutans 1431:1436 arg1 GalE 1450:1453 the other S. mutans 4-epimerase GalE 1418:1453 the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis 1418:1517 Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis, demonstrated that GalE is a UDP-Glc-4-epimerase while PgfE is a GlcNAc-4-epimerase. 36637425 0 10 theme carbon 93:98 arg1 metabolism 100:109 carbon metabolism 93:109 carbon metabolism 93:109 Involvement of the Streptococcus mutans PgfE and GalE 4-epimerases in protein glycosylation, carbon metabolism and cell division. 36637425 5 11 from binding 875:881 arg1 model 1009:1013 the Galleria mellonella invertebrate model 972:1013 the Galleria mellonella invertebrate model 972:1013 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 2 12 theme tooth 289:293 arg1 surfaces 295:302 tooth surfaces 289:302 tooth surfaces 289:302 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 5 13 theme endothelial 926:936 arg1 cells 938:942 human coronary artery endothelial cells 904:942 human coronary artery endothelial cells 904:942 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 4 14 theme virulence 583:591 arg1 properties 593:602 These virulence properties 577:602 These virulence properties 577:602 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 11 15 theme CBP 1903:1905 arg1 modifications 1878:1890 the PTM modifications 1870:1890 the PTM modifications of the key CBP, Cnm 1870:1910 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 3 16 theme oral 532:535 arg1 cells 570:574 oral epithelial and heart endothelial cells 532:574 oral epithelial and heart endothelial cells 532:574 One of the best characterized CBPs of S. mutans is Cnm which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. 36637425 3 17 theme mutans 472:477 arg1 CBPs 461:464 the best characterized CBPs 438:464 the best characterized CBPs of S. mutans 438:477 One of the best characterized CBPs of S. mutans is Cnm which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. 36637425 11 18 link O-linked 1783:1790 arg1 glycosylation 1800:1812 O-linked protein glycosylation 1783:1812 O-linked protein glycosylation 1783:1812 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 10 19 theme cell 1720:1723 arg1 division 1725:1732 cell division 1720:1732 cell division 1720:1732 While PgfE exclusively participates in protein O-glycosylation, we found that GalE affects galactose metabolism and cell division. 36637425 5 20 theme attenuated 948:957 arg1 virulence 959:967 attenuated virulence 948:967 attenuated virulence in the Galleria mellonella invertebrate model 948:1013 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 5 21 theme genes 841:845 arg1 Inactivation 807:818 Inactivation 807:818 Inactivation of the S. mutans pgf genes 807:845 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 5 22 theme mutans 830:835 arg1 genes 841:845 the S. mutans pgf genes 823:845 the S. mutans pgf genes 823:845 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 7 23 theme threonine-rich 1182:1195 arg1 repeats 1197:1203 only two threonine-rich repeats 1173:1203 only two threonine-rich repeats 1173:1203 Using a truncated Cnm variant containing only two threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. 36637425 11 24 theme protein 1792:1798 arg1 glycosylation 1800:1812 O-linked protein glycosylation 1783:1812 O-linked protein glycosylation 1783:1812 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 11 25 theme glycosylation 1800:1812 arg1 importance 1769:1778 the importance 1765:1778 the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans 1765:1853 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 5 26 from invasion 892:899 arg1 model 1009:1013 the Galleria mellonella invertebrate model 972:1013 the Galleria mellonella invertebrate model 972:1013 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 2 27 theme robust 270:275 arg1 biofilms 277:284 robust biofilms 270:284 robust biofilms on tooth surfaces 270:302 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 5 28 theme pgf 837:839 arg1 genes 841:845 the S. mutans pgf genes 823:845 the S. mutans pgf genes 823:845 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 10 29 theme protein 1643:1649 arg1 O-glycosylation 1651:1665 protein O-glycosylation 1643:1665 protein O-glycosylation 1643:1665 While PgfE exclusively participates in protein O-glycosylation, we found that GalE affects galactose metabolism and cell division. 36637425 7 30 theme spectrometric 1211:1223 arg1 analysis 1225:1232 mass spectrometric analysis 1206:1232 mass spectrometric analysis 1206:1232 Using a truncated Cnm variant containing only two threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. 36637425 11 31 theme key 1899:1901 arg1 Cnm 1908:1910 Cnm 1908:1910 Cnm 1908:1910 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 11 31 theme key 1899:1901 arg1 CBP 1903:1905 the key CBP 1895:1905 the key CBP 1895:1905 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 5 32 theme human 904:908 arg1 cells 938:942 human coronary artery endothelial cells 904:942 human coronary artery endothelial cells 904:942 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 4 33 dep enzymes 769:775 arg1 PgfM1 784:788 PgfM1 784:788 PgfM1 784:788 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 4 33 dep enzymes 769:775 arg1 enzymes 769:775 four enzymes 764:775 four enzymes: PgfS, PgfM1, PgfE and PgfM2 764:804 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 4 33 dep enzymes 769:775 arg1 PgfS 778:781 PgfS 778:781 PgfS 778:781 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 4 33 dep enzymes 769:775 arg1 PgfM2 800:804 PgfM2 800:804 PgfM2 800:804 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 4 33 dep enzymes 769:775 arg1 PgfE 791:794 PgfE 791:794 PgfE 791:794 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 2 34 theme collagenous 373:383 arg1 substrates 385:394 collagenous substrates 373:394 collagenous substrates including dentin and heart valves 373:428 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 2 34 theme collagenous 373:383 arg1 dentin 406:411 dentin 406:411 dentin 406:411 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 2 34 theme collagenous 373:383 arg1 valves 423:428 heart valves 417:428 heart valves 417:428 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 11 35 theme metabolism 1831:1840 arg1 importance 1769:1778 the importance 1765:1778 the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans 1765:1853 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 4 36 theme Pgf 717:719 arg1 machinery 735:743 the Pgf glycosylation machinery 713:743 the Pgf glycosylation machinery 713:743 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 3 37 theme endothelial 558:568 arg1 cells 570:574 oral epithelial and heart endothelial cells 532:574 oral epithelial and heart endothelial cells 532:574 One of the best characterized CBPs of S. mutans is Cnm which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. 36637425 1 38 theme dental 185:190 arg1 caries 192:197 dental caries 185:197 dental caries 185:197 Streptococcus mutans is a key pathogen associated with dental caries and is often implicated in infective endocarditis. 36637425 7 39 theme Cnm 1150:1152 arg1 variant 1154:1160 a truncated Cnm variant 1138:1160 a truncated Cnm variant containing only two threonine-rich repeats 1138:1203 Using a truncated Cnm variant containing only two threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. 36637425 10 40 theme galactose 1695:1703 arg1 metabolism 1705:1714 galactose metabolism 1695:1714 galactose metabolism 1695:1714 While PgfE exclusively participates in protein O-glycosylation, we found that GalE affects galactose metabolism and cell division. 36637425 8 41 theme lectin 1323:1328 arg1 blotting 1330:1337 lectin blotting 1323:1337 lectin blotting 1323:1337 Compositional analysis, complemented with lectin blotting, identified the HexNAc2 moieties as GlcNAc and GalNAc. 36637425 7 42 contain containing 1162:1171 arg1 variant 1154:1160 a truncated Cnm variant 1138:1160 a truncated Cnm variant containing only two threonine-rich repeats 1138:1203 Using a truncated Cnm variant containing only two threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. 36637425 7 42 contain containing 1162:1171 arg2 repeats 1197:1203 only two threonine-rich repeats 1173:1203 only two threonine-rich repeats 1173:1203 Using a truncated Cnm variant containing only two threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. 36637425 3 43 theme epithelial 537:546 arg1 cells 570:574 oral epithelial and heart endothelial cells 532:574 oral epithelial and heart endothelial cells 532:574 One of the best characterized CBPs of S. mutans is Cnm which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. 36637425 9 44 with Comparison 1394:1403 arg1 GalE 1450:1453 the other S. mutans 4-epimerase GalE 1418:1453 the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis 1418:1517 Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis, demonstrated that GalE is a UDP-Glc-4-epimerase while PgfE is a GlcNAc-4-epimerase. 36637425 3 45 theme CBPs 461:464 arg1 CBPs 461:464 the best characterized CBPs 438:464 the best characterized CBPs of S. mutans 438:477 One of the best characterized CBPs of S. mutans is Cnm which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. 36637425 3 45 theme CBPs 461:464 arg1 One 431:433 One 431:433 One 431:433 One of the best characterized CBPs of S. mutans is Cnm which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. 36637425 5 46 theme coronary 910:917 arg1 cells 938:942 human coronary artery endothelial cells 904:942 human coronary artery endothelial cells 904:942 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 0 47 theme cell 115:118 arg1 division 120:127 cell division 115:127 cell division 115:127 Involvement of the Streptococcus mutans PgfE and GalE 4-epimerases in protein glycosylation, carbon metabolism and cell division. 36637425 11 48 theme carbohydrate 1818:1829 arg1 metabolism 1831:1840 carbohydrate metabolism 1818:1840 carbohydrate metabolism 1818:1840 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 4 49 theme repeat 696:701 arg1 region 703:708 the Cnm threonine-rich repeat region 673:708 the Cnm threonine-rich repeat region 673:708 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 2 50 theme heart 417:421 arg1 valves 423:428 heart valves 417:428 heart valves 417:428 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 0 51 theme PgfE 40:43 arg1 Involvement 0:10 Involvement 0:10 Involvement of the Streptococcus mutans PgfE and GalE 0:52 Involvement of the Streptococcus mutans PgfE and GalE 4-epimerases in protein glycosylation, carbon metabolism and cell division. 36637425 9 52 dep UDP-Glc-4-epimerase 1548:1566 arg1 PgfE 1574:1577 PgfE 1574:1577 PgfE 1574:1577 Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis, demonstrated that GalE is a UDP-Glc-4-epimerase while PgfE is a GlcNAc-4-epimerase. 36637425 9 52 dep UDP-Glc-4-epimerase 1548:1566 arg1 GlcNAc-4-epimerase 1584:1601 a GlcNAc-4-epimerase 1582:1601 a GlcNAc-4-epimerase 1582:1601 Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis, demonstrated that GalE is a UDP-Glc-4-epimerase while PgfE is a GlcNAc-4-epimerase. 36637425 5 53 theme invertebrate 996:1007 arg1 model 1009:1013 the Galleria mellonella invertebrate model 972:1013 the Galleria mellonella invertebrate model 972:1013 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 7 54 theme truncated 1140:1148 arg1 variant 1154:1160 a truncated Cnm variant 1138:1160 a truncated Cnm variant containing only two threonine-rich repeats 1138:1203 Using a truncated Cnm variant containing only two threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. 36637425 11 55 theme O-linked 1783:1790 arg1 glycosylation 1800:1812 O-linked protein glycosylation 1783:1812 O-linked protein glycosylation 1783:1812 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 3 56 theme characterized 447:459 arg1 CBPs 461:464 the best characterized CBPs 438:464 the best characterized CBPs of S. mutans 438:477 One of the best characterized CBPs of S. mutans is Cnm which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. 36637425 0 57 theme GalE 49:52 arg1 Involvement 0:10 Involvement 0:10 Involvement of the Streptococcus mutans PgfE and GalE 0:52 Involvement of the Streptococcus mutans PgfE and GalE 4-epimerases in protein glycosylation, carbon metabolism and cell division. 36637425 9 58 theme structural 1463:1472 arg1 modeling 1474:1481 structural modeling 1463:1481 structural modeling 1463:1481 Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis, demonstrated that GalE is a UDP-Glc-4-epimerase while PgfE is a GlcNAc-4-epimerase. 36637425 6 59 theme present 1020:1026 arg1 study 1028:1032 The present study 1016:1032 The present study 1016:1032 The present study aimed to better understand Cnm glycosylation and to characterize the predicted 4-epimerase, PgfE. 36637425 3 60 theme cells 570:574 arg1 invasion 520:527 invasion 520:527 invasion 520:527 One of the best characterized CBPs of S. mutans is Cnm which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. 36637425 3 60 theme cells 570:574 arg1 adhesion 507:514 adhesion 507:514 adhesion 507:514 One of the best characterized CBPs of S. mutans is Cnm which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. 36637425 11 61 theme PTM 1874:1876 arg1 modifications 1878:1890 the PTM modifications 1870:1890 the PTM modifications of the key CBP, Cnm 1870:1910 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 4 62 attach linked 622:627 arg1 modification 651:662 post-translational modification 632:662 post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2 632:804 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 4 62 attach linked 622:627 arg2 properties 593:602 These virulence properties 577:602 These virulence properties 577:602 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 4 62 attach linked 622:627 arg1 PTM 665:667 PTM 665:667 PTM 665:667 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 5 63 theme reduced 884:890 arg1 invasion 892:899 reduced invasion 884:899 reduced invasion of human coronary artery endothelial cells 884:942 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 2 64 from biofilms 277:284 arg1 surfaces 295:302 tooth surfaces 289:302 tooth surfaces 289:302 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 11 65 mod modifications 1878:1890 arg1 Cnm 1908:1910 Cnm 1908:1910 Cnm 1908:1910 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 11 65 mod modifications 1878:1890 arg3 PTM 1874:1876 the PTM modifications 1870:1890 the PTM modifications of the key CBP, Cnm 1870:1910 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 11 65 mod modifications 1878:1890 arg1 CBP 1903:1905 the key CBP 1895:1905 the key CBP 1895:1905 This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm. 36637425 2 66 theme binding 325:331 arg1 proteins 333:340 collagen binding proteins 316:340 collagen binding proteins (CBPs) 316:347 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 2 66 theme binding 325:331 arg1 CBPs 343:346 CBPs 343:346 CBPs 343:346 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 5 67 theme artery 919:924 arg1 cells 938:942 human coronary artery endothelial cells 904:942 human coronary artery endothelial cells 904:942 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 9 68 theme PgfE 1408:1411 arg1 Comparison 1394:1403 Comparison 1394:1403 Comparison 1394:1403 Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis, demonstrated that GalE is a UDP-Glc-4-epimerase while PgfE is a GlcNAc-4-epimerase. 36637425 5 69 theme cells 938:942 arg1 binding 875:881 decreased collagen binding 856:881 decreased collagen binding 856:881 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 5 69 theme cells 938:942 arg1 invasion 892:899 reduced invasion 884:899 reduced invasion of human coronary artery endothelial cells 884:942 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 5 69 theme cells 938:942 arg1 virulence 959:967 attenuated virulence 948:967 attenuated virulence in the Galleria mellonella invertebrate model 948:1013 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 2 70 theme collagen 316:323 arg1 proteins 333:340 collagen binding proteins 316:340 collagen binding proteins (CBPs) 316:347 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 2 70 theme collagen 316:323 arg1 CBPs 343:346 CBPs 343:346 CBPs 343:346 This organism forms robust biofilms on tooth surfaces and can use collagen binding proteins (CBPs) to efficiently colonize collagenous substrates including dentin and heart valves. 36637425 8 71 theme HexNAc2 1355:1361 arg1 moieties 1363:1370 the HexNAc2 moieties 1351:1370 the HexNAc2 moieties 1351:1370 Compositional analysis, complemented with lectin blotting, identified the HexNAc2 moieties as GlcNAc and GalNAc. 36637425 4 72 theme glycosylation 721:733 arg1 machinery 735:743 the Pgf glycosylation machinery 713:743 the Pgf glycosylation machinery 713:743 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 9 73 theme capillary 1493:1501 arg1 electrophoresis 1503:1517 capillary electrophoresis 1493:1517 capillary electrophoresis 1493:1517 Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis, demonstrated that GalE is a UDP-Glc-4-epimerase while PgfE is a GlcNAc-4-epimerase. 36637425 5 74 theme decreased 856:864 arg1 binding 875:881 decreased collagen binding 856:881 decreased collagen binding 856:881 Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells and attenuated virulence in the Galleria mellonella invertebrate model. 36637425 4 75 theme post-translational 632:649 arg1 modification 651:662 post-translational modification 632:662 post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2 632:804 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 4 75 theme post-translational 632:649 arg1 PTM 665:667 PTM 665:667 PTM 665:667 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 4 76 theme threonine-rich 681:694 arg1 region 703:708 the Cnm threonine-rich repeat region 673:708 the Cnm threonine-rich repeat region 673:708 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 6 77 theme Cnm 1061:1063 arg1 glycosylation 1065:1077 Cnm glycosylation 1061:1077 Cnm glycosylation 1061:1077 The present study aimed to better understand Cnm glycosylation and to characterize the predicted 4-epimerase, PgfE. 36637425 1 78 theme infective 226:234 arg1 endocarditis 236:247 infective endocarditis 226:247 infective endocarditis 226:247 Streptococcus mutans is a key pathogen associated with dental caries and is often implicated in infective endocarditis. 36637425 9 79 theme 4-epimerase 1438:1448 arg1 GalE 1450:1453 the other S. mutans 4-epimerase GalE 1418:1453 the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis 1418:1517 Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis, demonstrated that GalE is a UDP-Glc-4-epimerase while PgfE is a GlcNAc-4-epimerase. 36637425 6 80 theme predicted 1103:1111 arg1 4-epimerase 1113:1123 the predicted 4-epimerase 1099:1123 the predicted 4-epimerase 1099:1123 The present study aimed to better understand Cnm glycosylation and to characterize the predicted 4-epimerase, PgfE. 36637425 6 80 theme predicted 1103:1111 arg1 PgfE 1126:1129 PgfE 1126:1129 PgfE 1126:1129 The present study aimed to better understand Cnm glycosylation and to characterize the predicted 4-epimerase, PgfE. 36637425 8 81 theme Compositional 1281:1293 arg1 analysis 1295:1302 Compositional analysis 1281:1302 Compositional analysis 1281:1302 Compositional analysis, complemented with lectin blotting, identified the HexNAc2 moieties as GlcNAc and GalNAc. 36637425 4 82 theme Cnm 677:679 arg1 region 703:708 the Cnm threonine-rich repeat region 673:708 the Cnm threonine-rich repeat region 673:708 These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of four enzymes: PgfS, PgfM1, PgfE and PgfM2. 36637425 7 83 theme extensive 1243:1251 arg1 glycosylation 1253:1265 extensive glycosylation 1243:1265 extensive glycosylation with HexNAc2 1243:1278 Using a truncated Cnm variant containing only two threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. 36637425 9 84 theme other 1422:1426 arg1 GalE 1450:1453 the other S. mutans 4-epimerase GalE 1418:1453 the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis 1418:1517 Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, NMR, and capillary electrophoresis, demonstrated that GalE is a UDP-Glc-4-epimerase while PgfE is a GlcNAc-4-epimerase. 36002036 2 0 theme Syndrome 499:506 arg1 edge 471:474 the edge 467:474 the edge of the Williams-Beuren Syndrome (WBS) 467:512 GALNT17, also known as WBSCR17, is located at the edge of the Williams-Beuren Syndrome (WBS) critical region and adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated. 36002036 7 1 theme new 1541:1543 arg1 clues 1545:1549 new clues 1541:1549 new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients 1541:1639 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 4 2 theme molecular 858:866 arg1 phenotypes 868:877 molecular phenotypes 858:877 molecular phenotypes exhibited by Galnt17 knockout (Galnt17-/-) mice 858:925 In this study, we have analyzed behavioral, brain pathology, and molecular phenotypes exhibited by Galnt17 knockout (Galnt17-/-) mice. 36002036 3 3 theme in 734:735 arg1 functions 742:750 the in vivo functions 730:750 the in vivo functions of this gene 730:763 Although previous data have implicated Galnt17 in neurodevelopment, the in vivo functions of this gene have not been investigated. 36002036 6 4 theme Transcriptomic 1104:1117 arg1 analysis 1131:1138 Transcriptomic and protein analysis 1104:1138 analysis 1131:1138 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 6 5 theme synaptic 1352:1359 arg1 signaling 1361:1369 synaptic signaling 1352:1369 synaptic signaling 1352:1369 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 1 6 theme proteins 289:296 arg1 glycosylation 265:277 mucin-type O-linked glycosylation 245:277 mucin-type O-linked glycosylation of target proteins 245:296 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 2 7 theme Williams-Beuren 483:497 arg1 WBS 509:511 WBS 509:511 WBS 509:511 GALNT17, also known as WBSCR17, is located at the edge of the Williams-Beuren Syndrome (WBS) critical region and adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated. 36002036 2 7 theme Williams-Beuren 483:497 arg1 Syndrome 499:506 the Williams-Beuren Syndrome 479:506 the Williams-Beuren Syndrome (WBS) 479:512 GALNT17, also known as WBSCR17, is located at the edge of the Williams-Beuren Syndrome (WBS) critical region and adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated. 36002036 2 8 theme neurodevelopmental 595:612 arg1 phenotypes 614:623 neurodevelopmental phenotypes 595:623 neurodevelopmental phenotypes that are thought to be co-regulated 595:659 GALNT17, also known as WBSCR17, is located at the edge of the Williams-Beuren Syndrome (WBS) critical region and adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated. 36002036 1 9 gly glycosylation 265:277 arg1 proteins 289:296 target proteins 282:296 target proteins 282:296 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 1 10 theme N-acetylgalactosaminyltransferase 167:199 arg1 protein 212:218 a N-acetylgalactosaminyltransferase (GalNAc-T) protein 165:218 a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins 165:296 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 1 10 theme N-acetylgalactosaminyltransferase 167:199 arg1 GALNT17 149:155 GALNT17 149:155 GALNT17 149:155 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 1 10 theme N-acetylgalactosaminyltransferase 167:199 arg1 process 301:307 a process 299:307 a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing 299:418 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 6 11 theme axon 1330:1333 arg1 pathfinding 1335:1345 axon pathfinding 1330:1345 axon pathfinding 1330:1345 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 0 12 theme social 95:100 arg1 interactions 102:113 social interactions 95:113 social interactions with cerebellar vermis pathology 95:146 Galnt17 loss-of-function leads to developmental delay and abnormal coordination, activity, and social interactions with cerebellar vermis pathology. 36002036 1 13 theme neurite 381:387 arg1 outgrowth 389:397 neurite outgrowth 381:397 neurite outgrowth 381:397 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 0 14 with activity 81:88 arg1 pathology 138:146 cerebellar vermis pathology 120:146 cerebellar vermis pathology 120:146 Galnt17 loss-of-function leads to developmental delay and abnormal coordination, activity, and social interactions with cerebellar vermis pathology. 36002036 7 15 theme specific 1482:1489 arg1 role 1491:1494 a specific role 1480:1494 a specific role for Galnt17 in brain development 1480:1527 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 7 16 from role 1491:1494 arg1 development 1517:1527 brain development 1511:1527 brain development 1511:1527 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 2 17 dep adjacent 534:541 arg1 genomic 563:569 genomic 563:569 genomic 563:569 GALNT17, also known as WBSCR17, is located at the edge of the Williams-Beuren Syndrome (WBS) critical region and adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated. 36002036 2 18 from edge 471:474 arg1 located 456:462 located 456:462 located 456:462 GALNT17, also known as WBSCR17, is located at the edge of the Williams-Beuren Syndrome (WBS) critical region and adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated. 36002036 6 19 theme neuron 1306:1311 arg1 differentiation 1313:1327 neuron differentiation 1306:1327 neuron differentiation 1306:1327 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 6 20 theme sulfate 1207:1213 arg1 synthesis 1215:1223 heparan sulfate synthesis 1199:1223 heparan sulfate synthesis 1199:1223 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 3 21 dep in 734:735 arg1 vivo 737:740 vivo 737:740 vivo 737:740 Although previous data have implicated Galnt17 in neurodevelopment, the in vivo functions of this gene have not been investigated. 36002036 7 22 theme certain 1601:1607 arg1 WBS 1609:1611 certain WBS and AUTS2 syndrome patients 1601:1639 WBS 1609:1611 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 2 23 theme critical 514:521 arg1 region 523:528 critical region 514:528 critical region 514:528 GALNT17, also known as WBSCR17, is located at the edge of the Williams-Beuren Syndrome (WBS) critical region and adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated. 36002036 7 24 theme brain 1511:1515 arg1 development 1517:1527 brain development 1511:1527 brain development 1511:1527 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 4 25 theme brain 837:841 arg1 pathology 843:851 brain pathology 837:851 brain pathology 837:851 In this study, we have analyzed behavioral, brain pathology, and molecular phenotypes exhibited by Galnt17 knockout (Galnt17-/-) mice. 36002036 0 26 with coordination 67:78 arg1 pathology 138:146 cerebellar vermis pathology 120:146 cerebellar vermis pathology 120:146 Galnt17 loss-of-function leads to developmental delay and abnormal coordination, activity, and social interactions with cerebellar vermis pathology. 36002036 5 27 theme developmental 968:980 arg1 neuropathology 982:995 developmental neuropathology 968:995 developmental neuropathology 968:995 We show that Galnt17-/- mutants exhibit developmental neuropathology within the cerebellar vermis, along with abnormal activity, coordination, and social interaction deficits. 36002036 4 28 theme Galnt17-/- 910:919 arg1 mice 922:925 Galnt17 knockout (Galnt17-/-) mice 892:925 Galnt17 knockout (Galnt17-/-) mice 892:925 In this study, we have analyzed behavioral, brain pathology, and molecular phenotypes exhibited by Galnt17 knockout (Galnt17-/-) mice. 36002036 7 29 from phenotypes 1587:1596 arg1 WBS 1609:1611 certain WBS and AUTS2 syndrome patients 1601:1639 WBS 1609:1611 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 7 29 from phenotypes 1587:1596 arg1 patients 1632:1639 certain WBS and AUTS2 syndrome patients 1601:1639 patients 1632:1639 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 6 30 theme mutant 1392:1397 arg1 neuropathology 1399:1412 the mutant neuropathology 1388:1412 the mutant neuropathology 1388:1412 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 6 31 theme central 1295:1301 arg1 pathways 1286:1293 pathways 1286:1293 pathways central to neuron differentiation, axon pathfinding, and synaptic signaling 1286:1369 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 2 32 theme located 456:462 arg1 region 523:528 critical region 514:528 critical region 514:528 GALNT17, also known as WBSCR17, is located at the edge of the Williams-Beuren Syndrome (WBS) critical region and adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated. 36002036 1 33 theme GalNAc-T 202:209 arg1 protein 212:218 a N-acetylgalactosaminyltransferase (GalNAc-T) protein 165:218 a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins 165:296 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 1 33 theme GalNAc-T 202:209 arg1 GALNT17 149:155 GALNT17 149:155 GALNT17 149:155 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 1 33 theme GalNAc-T 202:209 arg1 process 301:307 a process 299:307 a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing 299:418 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 1 34 theme neurite 404:410 arg1 sensing 412:418 neurite sensing 404:418 neurite sensing 404:418 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 6 35 theme pathways 1286:1293 arg1 disruption 1272:1281 disruption 1272:1281 disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling 1272:1369 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 0 36 with interactions 102:113 arg1 pathology 138:146 cerebellar vermis pathology 120:146 cerebellar vermis pathology 120:146 Galnt17 loss-of-function leads to developmental delay and abnormal coordination, activity, and social interactions with cerebellar vermis pathology. 36002036 7 37 theme molecular 1457:1465 arg1 data 1467:1470 molecular data 1457:1470 molecular data 1457:1470 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 6 38 with consistent 1372:1381 arg1 neuropathology 1399:1412 the mutant neuropathology 1388:1412 the mutant neuropathology 1388:1412 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 0 39 theme Galnt17 0:6 arg1 loss-of-function 8:23 Galnt17 loss-of-function 0:23 Galnt17 loss-of-function 0:23 Galnt17 loss-of-function leads to developmental delay and abnormal coordination, activity, and social interactions with cerebellar vermis pathology. 36002036 1 40 theme important 309:317 arg1 protein 212:218 a N-acetylgalactosaminyltransferase (GalNAc-T) protein 165:218 a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins 165:296 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 1 40 theme important 309:317 arg1 process 301:307 a process 299:307 a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing 299:418 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 3 41 theme gene 760:763 arg1 functions 742:750 the in vivo functions 730:750 the in vivo functions of this gene 730:763 Although previous data have implicated Galnt17 in neurodevelopment, the in vivo functions of this gene have not been investigated. 36002036 1 42 link O-linked 256:263 arg1 glycosylation 265:277 mucin-type O-linked glycosylation 245:277 mucin-type O-linked glycosylation of target proteins 245:296 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 6 43 theme type 1174:1177 arg1 O-glycosylation 1179:1193 mucin type O-glycosylation 1168:1193 mucin type O-glycosylation 1168:1193 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 0 44 theme vermis 131:136 arg1 pathology 138:146 cerebellar vermis pathology 120:146 cerebellar vermis pathology 120:146 Galnt17 loss-of-function leads to developmental delay and abnormal coordination, activity, and social interactions with cerebellar vermis pathology. 36002036 7 45 theme brain 1421:1425 arg1 phenotypes 1442:1451 These brain and behavioral phenotypes 1415:1451 phenotypes 1442:1451 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 6 46 theme mucin 1168:1172 arg1 O-glycosylation 1179:1193 mucin type O-glycosylation 1168:1193 mucin type O-glycosylation 1168:1193 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 1 47 theme cell 323:326 arg1 adhesion 328:335 cell adhesion 323:335 cell adhesion 323:335 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 0 48 theme cerebellar 120:129 arg1 vermis 131:136 cerebellar vermis 120:136 cerebellar vermis pathology 120:146 Galnt17 loss-of-function leads to developmental delay and abnormal coordination, activity, and social interactions with cerebellar vermis pathology. 36002036 5 49 theme Galnt17-/- 941:950 arg1 mutants 952:958 Galnt17-/- mutants 941:958 Galnt17-/- mutants 941:958 We show that Galnt17-/- mutants exhibit developmental neuropathology within the cerebellar vermis, along with abnormal activity, coordination, and social interaction deficits. 36002036 5 50 theme social 1075:1080 arg1 deficits 1094:1101 social interaction deficits 1075:1101 social interaction deficits 1075:1101 We show that Galnt17-/- mutants exhibit developmental neuropathology within the cerebellar vermis, along with abnormal activity, coordination, and social interaction deficits. 36002036 0 51 theme developmental 34:46 arg1 delay 48:52 developmental delay 34:52 developmental delay 34:52 Galnt17 loss-of-function leads to developmental delay and abnormal coordination, activity, and social interactions with cerebellar vermis pathology. 36002036 2 52 theme adjacent 534:541 arg1 regions 571:577 adjacent to the AUTS2 locus, genomic regions 534:577 adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated 534:659 GALNT17, also known as WBSCR17, is located at the edge of the Williams-Beuren Syndrome (WBS) critical region and adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated. 36002036 5 53 theme interaction 1082:1092 arg1 deficits 1094:1101 social interaction deficits 1075:1101 social interaction deficits 1075:1101 We show that Galnt17-/- mutants exhibit developmental neuropathology within the cerebellar vermis, along with abnormal activity, coordination, and social interaction deficits. 36002036 7 54 theme behavioral 1431:1440 arg1 phenotypes 1442:1451 These brain and behavioral phenotypes 1415:1451 phenotypes 1442:1451 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 1 55 theme mucin-type 245:254 arg1 glycosylation 265:277 mucin-type O-linked glycosylation 245:277 mucin-type O-linked glycosylation of target proteins 245:296 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 0 56 theme abnormal 58:65 arg1 coordination 67:78 abnormal coordination 58:78 abnormal coordination 58:78 Galnt17 loss-of-function leads to developmental delay and abnormal coordination, activity, and social interactions with cerebellar vermis pathology. 36002036 1 57 theme cell 338:341 arg1 signaling 343:351 cell signaling 338:351 cell signaling 338:351 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 4 58 theme Galnt17 892:898 arg1 mice 922:925 Galnt17 knockout (Galnt17-/-) mice 892:925 Galnt17 knockout (Galnt17-/-) mice 892:925 In this study, we have analyzed behavioral, brain pathology, and molecular phenotypes exhibited by Galnt17 knockout (Galnt17-/-) mice. 36002036 2 59 theme AUTS2 550:554 arg1 locus 556:560 the AUTS2 locus 546:560 the AUTS2 locus 546:560 GALNT17, also known as WBSCR17, is located at the edge of the Williams-Beuren Syndrome (WBS) critical region and adjacent to the AUTS2 locus, genomic regions associated with neurodevelopmental phenotypes that are thought to be co-regulated. 36002036 5 60 theme abnormal 1038:1045 arg1 activity 1047:1054 abnormal activity 1038:1054 abnormal activity 1038:1054 We show that Galnt17-/- mutants exhibit developmental neuropathology within the cerebellar vermis, along with abnormal activity, coordination, and social interaction deficits. 36002036 6 61 theme mutant 1243:1248 arg1 cerebellum 1250:1259 the developing mutant cerebellum 1228:1259 the developing mutant cerebellum 1228:1259 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 6 62 from reductions 1149:1158 arg1 O-glycosylation 1179:1193 mucin type O-glycosylation 1168:1193 mucin type O-glycosylation 1168:1193 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 6 62 from reductions 1149:1158 arg1 cerebellum 1250:1259 the developing mutant cerebellum 1228:1259 the developing mutant cerebellum 1228:1259 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 6 62 from reductions 1149:1158 arg1 synthesis 1215:1223 heparan sulfate synthesis 1199:1223 heparan sulfate synthesis 1199:1223 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 1 63 theme O-linked 256:263 arg1 glycosylation 265:277 mucin-type O-linked glycosylation 245:277 mucin-type O-linked glycosylation of target proteins 245:296 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 4 64 theme knockout 900:907 arg1 mice 922:925 Galnt17 knockout (Galnt17-/-) mice 892:925 Galnt17 knockout (Galnt17-/-) mice 892:925 In this study, we have analyzed behavioral, brain pathology, and molecular phenotypes exhibited by Galnt17 knockout (Galnt17-/-) mice. 36002036 3 65 theme previous 671:678 arg1 data 680:683 previous data 671:683 previous data 671:683 Although previous data have implicated Galnt17 in neurodevelopment, the in vivo functions of this gene have not been investigated. 36002036 6 66 theme developing 1232:1241 arg1 cerebellum 1250:1259 the developing mutant cerebellum 1228:1259 the developing mutant cerebellum 1228:1259 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 5 67 theme cerebellar 1008:1017 arg1 vermis 1019:1024 the cerebellar vermis 1004:1024 the cerebellar vermis 1004:1024 We show that Galnt17-/- mutants exhibit developmental neuropathology within the cerebellar vermis, along with abnormal activity, coordination, and social interaction deficits. 36002036 6 68 theme protein 1123:1129 arg1 analysis 1131:1138 Transcriptomic and protein analysis 1104:1138 analysis 1131:1138 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 6 69 theme heparan 1199:1205 arg1 sulfate 1207:1213 heparan sulfate 1199:1213 heparan sulfate synthesis 1199:1223 Transcriptomic and protein analysis revealed reductions in both mucin type O-glycosylation and heparan sulfate synthesis in the developing mutant cerebellum along with disruption of pathways central to neuron differentiation, axon pathfinding, and synaptic signaling, consistent with the mutant neuropathology. 36002036 7 70 theme AUTS2 1617:1621 arg1 patients 1632:1639 certain WBS and AUTS2 syndrome patients 1601:1639 patients 1632:1639 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 1 71 theme neurotransmitter 354:369 arg1 activity 371:378 neurotransmitter activity 354:378 neurotransmitter activity 354:378 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 36002036 7 72 theme syndrome 1623:1630 arg1 patients 1632:1639 certain WBS and AUTS2 syndrome patients 1601:1639 patients 1632:1639 These brain and behavioral phenotypes and molecular data confirm a specific role for Galnt17 in brain development and suggest new clues to factors that could contribute to phenotypes in certain WBS and AUTS2 syndrome patients. 36002036 0 73 with delay 48:52 arg1 pathology 138:146 cerebellar vermis pathology 120:146 cerebellar vermis pathology 120:146 Galnt17 loss-of-function leads to developmental delay and abnormal coordination, activity, and social interactions with cerebellar vermis pathology. 36002036 1 74 theme target 282:287 arg1 proteins 289:296 target proteins 282:296 target proteins 282:296 GALNT17 encodes a N-acetylgalactosaminyltransferase (GalNAc-T) protein specifically involved in mucin-type O-linked glycosylation of target proteins, a process important for cell adhesion, cell signaling, neurotransmitter activity, neurite outgrowth, and neurite sensing. 37379210 4 0 theme E3 519:520 arg1 ligase 522:527 an E3 ligase 516:527 an E3 ligase of deglycosylated PD-1 516:550 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 4 0 theme E3 519:520 arg1 minute 483:488 Murine double minute 2 469:490 Murine double minute 2 (MDM2) 469:497 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 5 1 theme PD-1 692:695 arg1 deglycosylation 697:711 subsequent NGLY1-catalyzed PD-1 deglycosylation 665:711 subsequent NGLY1-catalyzed PD-1 deglycosylation 665:711 In addition, the presence of MDM2 facilitates glycosylated PD-1 interaction with glycosidase NGLY1 and promotes subsequent NGLY1-catalyzed PD-1 deglycosylation. 37379210 6 2 theme MDM2 779:782 arg1 absence 752:758 the absence 748:758 the absence of T cell-specific MDM2 748:782 Functionally, we demonstrate that the absence of T cell-specific MDM2 accelerates tumor growth by primarily upregulating PD-1. 37379210 4 3 theme deglycosylated 532:545 arg1 PD-1 547:550 deglycosylated PD-1 532:550 deglycosylated PD-1 532:550 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 8 4 theme PD-1 1070:1073 arg1 degradation 1075:1085 PD-1 degradation 1070:1085 PD-1 degradation 1070:1085 Our study reveals that MDM2 directs PD-1 degradation via a deglycosylation-ubiquitination coupled mechanism and sheds light on a promising strategy to boost cancer immunotherapy by targeting the T cell-specific MDM2-PD-1 regulatory axis. 37379210 3 5 theme glycosylation 386:398 arg1 removal 366:372 the removal 362:372 the removal of N-linked glycosylation 362:398 We show that the removal of N-linked glycosylation is a prerequisite for efficient PD-1 ubiquitination and degradation. 37379210 3 5 theme glycosylation 386:398 arg1 prerequisite 405:416 a prerequisite 403:416 a prerequisite for efficient PD-1 ubiquitination and degradation 403:466 We show that the removal of N-linked glycosylation is a prerequisite for efficient PD-1 ubiquitination and degradation. 37379210 7 6 theme anti-PD-1 1009:1017 arg1 immunotherapy 1019:1031 anti-PD-1 immunotherapy 1009:1031 anti-PD-1 immunotherapy 1009:1031 By stimulating the p53-MDM2 axis, interferon-α (IFN-α) reduces PD-1 levels in T cells, which, in turn, exhibit a synergistic effect on tumor suppression by sensitizing anti-PD-1 immunotherapy. 37379210 5 7 theme glycosidase 634:644 arg1 NGLY1 646:650 glycosidase NGLY1 634:650 glycosidase NGLY1 634:650 In addition, the presence of MDM2 facilitates glycosylated PD-1 interaction with glycosidase NGLY1 and promotes subsequent NGLY1-catalyzed PD-1 deglycosylation. 37379210 3 8 link N-linked 377:384 arg1 glycosylation 386:398 N-linked glycosylation 377:398 N-linked glycosylation 377:398 We show that the removal of N-linked glycosylation is a prerequisite for efficient PD-1 ubiquitination and degradation. 37379210 6 9 theme T cell-specific 763:777 arg1 MDM2 779:782 T cell-specific MDM2 763:782 T cell-specific MDM2 763:782 Functionally, we demonstrate that the absence of T cell-specific MDM2 accelerates tumor growth by primarily upregulating PD-1. 37379210 5 10 gly glycosylated 599:610 arg1 interaction 617:627 glycosylated PD-1 interaction 599:627 glycosylated PD-1 interaction with glycosidase NGLY1 599:650 In addition, the presence of MDM2 facilitates glycosylated PD-1 interaction with glycosidase NGLY1 and promotes subsequent NGLY1-catalyzed PD-1 deglycosylation. 37379210 8 11 theme regulatory 1255:1264 arg1 axis 1266:1269 the T cell-specific MDM2-PD-1 regulatory axis 1225:1269 the T cell-specific MDM2-PD-1 regulatory axis 1225:1269 Our study reveals that MDM2 directs PD-1 degradation via a deglycosylation-ubiquitination coupled mechanism and sheds light on a promising strategy to boost cancer immunotherapy by targeting the T cell-specific MDM2-PD-1 regulatory axis. 37379210 8 12 theme coupled 1124:1130 arg1 mechanism 1132:1140 a deglycosylation-ubiquitination coupled mechanism 1091:1140 a deglycosylation-ubiquitination coupled mechanism 1091:1140 Our study reveals that MDM2 directs PD-1 degradation via a deglycosylation-ubiquitination coupled mechanism and sheds light on a promising strategy to boost cancer immunotherapy by targeting the T cell-specific MDM2-PD-1 regulatory axis. 37379210 1 13 theme Posttranslational 87:103 arg1 modifications 105:117 Posttranslational modifications 87:117 Posttranslational modifications 87:117 Posttranslational modifications represent a key step in modulating programmed death-1 (PD-1) functions, but the underlying mechanisms remain incompletely defined. 37379210 3 14 theme N-linked 377:384 arg1 glycosylation 386:398 N-linked glycosylation 377:398 N-linked glycosylation 377:398 We show that the removal of N-linked glycosylation is a prerequisite for efficient PD-1 ubiquitination and degradation. 37379210 8 15 theme deglycosylation-ubiquitination 1093:1122 arg1 mechanism 1132:1140 a deglycosylation-ubiquitination coupled mechanism 1091:1140 a deglycosylation-ubiquitination coupled mechanism 1091:1140 Our study reveals that MDM2 directs PD-1 degradation via a deglycosylation-ubiquitination coupled mechanism and sheds light on a promising strategy to boost cancer immunotherapy by targeting the T cell-specific MDM2-PD-1 regulatory axis. 37379210 5 16 theme MDM2 582:585 arg1 presence 570:577 the presence 566:577 the presence of MDM2 566:585 In addition, the presence of MDM2 facilitates glycosylated PD-1 interaction with glycosidase NGLY1 and promotes subsequent NGLY1-catalyzed PD-1 deglycosylation. 37379210 7 17 theme PD-1 904:907 arg1 levels 909:914 PD-1 levels 904:914 PD-1 levels 904:914 By stimulating the p53-MDM2 axis, interferon-α (IFN-α) reduces PD-1 levels in T cells, which, in turn, exhibit a synergistic effect on tumor suppression by sensitizing anti-PD-1 immunotherapy. 37379210 0 18 theme deglycosylation-ubiquitination 8:37 arg1 cascade 39:45 deglycosylation-ubiquitination cascade 8:45 deglycosylation-ubiquitination cascade 8:45 Coupled deglycosylation-ubiquitination cascade in regulating PD-1 degradation by MDM2. 37379210 5 19 theme subsequent 665:674 arg1 deglycosylation 697:711 subsequent NGLY1-catalyzed PD-1 deglycosylation 665:711 subsequent NGLY1-catalyzed PD-1 deglycosylation 665:711 In addition, the presence of MDM2 facilitates glycosylated PD-1 interaction with glycosidase NGLY1 and promotes subsequent NGLY1-catalyzed PD-1 deglycosylation. 37379210 7 20 theme tumor 976:980 arg1 suppression 982:992 tumor suppression 976:992 tumor suppression 976:992 By stimulating the p53-MDM2 axis, interferon-α (IFN-α) reduces PD-1 levels in T cells, which, in turn, exhibit a synergistic effect on tumor suppression by sensitizing anti-PD-1 immunotherapy. 37379210 4 21 gly deglycosylated 532:545 arg1 PD-1 547:550 deglycosylated PD-1 532:550 deglycosylated PD-1 532:550 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 3 22 theme efficient 422:430 arg1 ubiquitination 437:450 efficient PD-1 ubiquitination 422:450 efficient PD-1 ubiquitination 422:450 We show that the removal of N-linked glycosylation is a prerequisite for efficient PD-1 ubiquitination and degradation. 37379210 5 23 theme NGLY1-catalyzed 676:690 arg1 deglycosylation 697:711 subsequent NGLY1-catalyzed PD-1 deglycosylation 665:711 subsequent NGLY1-catalyzed PD-1 deglycosylation 665:711 In addition, the presence of MDM2 facilitates glycosylated PD-1 interaction with glycosidase NGLY1 and promotes subsequent NGLY1-catalyzed PD-1 deglycosylation. 37379210 5 24 theme glycosylated 599:610 arg1 interaction 617:627 glycosylated PD-1 interaction 599:627 glycosylated PD-1 interaction with glycosidase NGLY1 599:650 In addition, the presence of MDM2 facilitates glycosylated PD-1 interaction with glycosidase NGLY1 and promotes subsequent NGLY1-catalyzed PD-1 deglycosylation. 37379210 1 25 theme underlying 199:208 arg1 mechanisms 210:219 the underlying mechanisms 195:219 the underlying mechanisms 195:219 Posttranslational modifications represent a key step in modulating programmed death-1 (PD-1) functions, but the underlying mechanisms remain incompletely defined. 37379210 7 26 theme synergistic 954:964 arg1 effect 966:971 a synergistic effect 952:971 a synergistic effect on tumor suppression 952:992 By stimulating the p53-MDM2 axis, interferon-α (IFN-α) reduces PD-1 levels in T cells, which, in turn, exhibit a synergistic effect on tumor suppression by sensitizing anti-PD-1 immunotherapy. 37379210 5 27 theme PD-1 612:615 arg1 interaction 617:627 glycosylated PD-1 interaction 599:627 glycosylated PD-1 interaction with glycosidase NGLY1 599:650 In addition, the presence of MDM2 facilitates glycosylated PD-1 interaction with glycosidase NGLY1 and promotes subsequent NGLY1-catalyzed PD-1 deglycosylation. 37379210 1 28 theme key 131:133 arg1 step 135:138 a key step 129:138 a key step in modulating programmed death-1 (PD-1) functions 129:188 Posttranslational modifications represent a key step in modulating programmed death-1 (PD-1) functions, but the underlying mechanisms remain incompletely defined. 37379210 7 29 theme p53-MDM2 860:867 arg1 axis 869:872 the p53-MDM2 axis 856:872 the p53-MDM2 axis 856:872 By stimulating the p53-MDM2 axis, interferon-α (IFN-α) reduces PD-1 levels in T cells, which, in turn, exhibit a synergistic effect on tumor suppression by sensitizing anti-PD-1 immunotherapy. 37379210 2 30 theme PD-1 333:336 arg1 stability 338:346 PD-1 stability 333:346 PD-1 stability 333:346 Here, we report crosstalk between deglycosylation and ubiquitination in regulating PD-1 stability. 37379210 0 31 theme PD-1 61:64 arg1 degradation 66:76 PD-1 degradation 61:76 PD-1 degradation 61:76 Coupled deglycosylation-ubiquitination cascade in regulating PD-1 degradation by MDM2. 37379210 8 32 theme MDM2-PD-1 1245:1253 arg1 axis 1266:1269 the T cell-specific MDM2-PD-1 regulatory axis 1225:1269 the T cell-specific MDM2-PD-1 regulatory axis 1225:1269 Our study reveals that MDM2 directs PD-1 degradation via a deglycosylation-ubiquitination coupled mechanism and sheds light on a promising strategy to boost cancer immunotherapy by targeting the T cell-specific MDM2-PD-1 regulatory axis. 37379210 3 33 theme PD-1 432:435 arg1 ubiquitination 437:450 efficient PD-1 ubiquitination 422:450 efficient PD-1 ubiquitination 422:450 We show that the removal of N-linked glycosylation is a prerequisite for efficient PD-1 ubiquitination and degradation. 37379210 4 34 theme PD-1 547:550 arg1 ligase 522:527 an E3 ligase 516:527 an E3 ligase of deglycosylated PD-1 516:550 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 4 34 theme PD-1 547:550 arg1 minute 483:488 Murine double minute 2 469:490 Murine double minute 2 (MDM2) 469:497 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 5 35 with interaction 617:627 arg1 NGLY1 646:650 glycosidase NGLY1 634:650 glycosidase NGLY1 634:650 In addition, the presence of MDM2 facilitates glycosylated PD-1 interaction with glycosidase NGLY1 and promotes subsequent NGLY1-catalyzed PD-1 deglycosylation. 37379210 8 36 theme promising 1163:1171 arg1 strategy 1173:1180 a promising strategy 1161:1180 a promising strategy to boost cancer immunotherapy by targeting the T cell-specific MDM2-PD-1 regulatory axis 1161:1269 Our study reveals that MDM2 directs PD-1 degradation via a deglycosylation-ubiquitination coupled mechanism and sheds light on a promising strategy to boost cancer immunotherapy by targeting the T cell-specific MDM2-PD-1 regulatory axis. 37379210 4 37 theme Murine 469:474 arg1 ligase 522:527 an E3 ligase 516:527 an E3 ligase of deglycosylated PD-1 516:550 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 4 37 theme Murine 469:474 arg1 minute 483:488 Murine double minute 2 469:490 Murine double minute 2 (MDM2) 469:497 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 4 37 theme Murine 469:474 arg1 MDM2 493:496 MDM2 493:496 MDM2 493:496 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 7 38 from effect 966:971 arg1 suppression 982:992 tumor suppression 976:992 tumor suppression 976:992 By stimulating the p53-MDM2 axis, interferon-α (IFN-α) reduces PD-1 levels in T cells, which, in turn, exhibit a synergistic effect on tumor suppression by sensitizing anti-PD-1 immunotherapy. 37379210 1 39 theme programmed 154:163 arg1 functions 180:188 programmed death-1 (PD-1) functions 154:188 programmed death-1 (PD-1) functions 154:188 Posttranslational modifications represent a key step in modulating programmed death-1 (PD-1) functions, but the underlying mechanisms remain incompletely defined. 37379210 8 40 theme T cell-specific 1229:1243 arg1 axis 1266:1269 the T cell-specific MDM2-PD-1 regulatory axis 1225:1269 the T cell-specific MDM2-PD-1 regulatory axis 1225:1269 Our study reveals that MDM2 directs PD-1 degradation via a deglycosylation-ubiquitination coupled mechanism and sheds light on a promising strategy to boost cancer immunotherapy by targeting the T cell-specific MDM2-PD-1 regulatory axis. 37379210 7 41 from levels 909:914 arg1 T cells 919:925 T cells 919:925 T cells 919:925 By stimulating the p53-MDM2 axis, interferon-α (IFN-α) reduces PD-1 levels in T cells, which, in turn, exhibit a synergistic effect on tumor suppression by sensitizing anti-PD-1 immunotherapy. 37379210 1 42 theme death-1 165:171 arg1 functions 180:188 programmed death-1 (PD-1) functions 154:188 programmed death-1 (PD-1) functions 154:188 Posttranslational modifications represent a key step in modulating programmed death-1 (PD-1) functions, but the underlying mechanisms remain incompletely defined. 37379210 4 43 theme double 476:481 arg1 ligase 522:527 an E3 ligase 516:527 an E3 ligase of deglycosylated PD-1 516:550 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 4 43 theme double 476:481 arg1 minute 483:488 Murine double minute 2 469:490 Murine double minute 2 (MDM2) 469:497 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 4 43 theme double 476:481 arg1 MDM2 493:496 MDM2 493:496 MDM2 493:496 Murine double minute 2 (MDM2) is identified as an E3 ligase of deglycosylated PD-1. 37379210 6 44 theme tumor 796:800 arg1 growth 802:807 tumor growth 796:807 tumor growth 796:807 Functionally, we demonstrate that the absence of T cell-specific MDM2 accelerates tumor growth by primarily upregulating PD-1. 37379210 8 45 theme cancer 1191:1196 arg1 immunotherapy 1198:1210 cancer immunotherapy 1191:1210 cancer immunotherapy 1191:1210 Our study reveals that MDM2 directs PD-1 degradation via a deglycosylation-ubiquitination coupled mechanism and sheds light on a promising strategy to boost cancer immunotherapy by targeting the T cell-specific MDM2-PD-1 regulatory axis. 37187248 1 0 theme Oliv 167:170 arg1 twigs 139:143 the twigs 135:143 the twigs of Phaeanthus lucidus Oliv 135:170 The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. 37187248 5 1 dep Phaeanthuslucidines 823:841 arg1 B 849:849 B 849:849 B 849:849 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 5 1 dep Phaeanthuslucidines 823:841 arg1 E 863:863 bidebiline E 852:863 bidebiline E 852:863 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 5 1 dep Phaeanthuslucidines 823:841 arg1 A 843:843 A 843:843 A 843:843 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 5 1 dep Phaeanthuslucidines 823:841 arg1 lanuginosine 870:881 lanuginosine 870:881 lanuginosine 870:881 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 5 1 dep Phaeanthuslucidines 823:841 arg1 Phaeanthuslucidines 823:841 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine 823:881 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine 823:881 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 5 2 theme α-glucosidase 890:902 arg1 activities 915:924 α-glucosidase inhibitory activities 890:924 α-glucosidase inhibitory activities 890:924 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 3 3 theme spectroscopic 517:529 arg1 data 531:534 spectroscopic data 517:534 spectroscopic data 517:534 Their structures were determined by extensive analysis of spectroscopic data, and by comparison of their spectroscopic and physical data with previous reports. 37187248 2 4 dep Resulted 173:180 arg1 phaeanthuslucidines 281:299 phaeanthuslucidines 281:299 phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds 281:456 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 3 5 theme data 591:594 arg1 comparison 544:553 comparison 544:553 comparison of their spectroscopic and physical data with previous reports 544:616 Their structures were determined by extensive analysis of spectroscopic data, and by comparison of their spectroscopic and physical data with previous reports. 37187248 5 6 theme 6.7-29.2 μM 959:969 arg1 range 950:954 the range 946:954 the range of 6.7-29.2 μM 946:969 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 3 7 theme spectroscopic 564:576 arg1 data 591:594 their spectroscopic and physical data 558:594 their spectroscopic and physical data 558:594 Their structures were determined by extensive analysis of spectroscopic data, and by comparison of their spectroscopic and physical data with previous reports. 37187248 6 8 theme docking 992:998 arg1 simulations 1000:1010 molecular docking simulations 982:1010 molecular docking simulations of α-glucosidase inhibition of active compounds 982:1058 Moreover, molecular docking simulations of α-glucosidase inhibition of active compounds were studied. 37187248 4 9 theme the 711:713 arg1 atropisomers 729:740 the (Ra) and (Sa) atropisomers 711:740 the (Ra) and (Sa) atropisomers 711:740 Phaeanthuslucidines A-C and bidebiline E were analysed and resolved by chiral HPLC to yield the (Ra) and (Sa) atropisomers, whose absolute configurations were respectively determined by ECD calculations. 37187248 6 10 theme molecular 982:990 arg1 simulations 1000:1010 molecular docking simulations 982:1010 molecular docking simulations of α-glucosidase inhibition of active compounds 982:1058 Moreover, molecular docking simulations of α-glucosidase inhibition of active compounds were studied. 37187248 4 11 theme bidebiline 647:656 arg1 E 658:658 bidebiline E 647:658 bidebiline E 647:658 Phaeanthuslucidines A-C and bidebiline E were analysed and resolved by chiral HPLC to yield the (Ra) and (Sa) atropisomers, whose absolute configurations were respectively determined by ECD calculations. 37187248 6 12 theme active 1043:1048 arg1 compounds 1050:1058 active compounds 1043:1058 active compounds 1043:1058 Moreover, molecular docking simulations of α-glucosidase inhibition of active compounds were studied. 37187248 4 13 theme chiral 690:695 arg1 HPLC 697:700 chiral HPLC 690:700 chiral HPLC 690:700 Phaeanthuslucidines A-C and bidebiline E were analysed and resolved by chiral HPLC to yield the (Ra) and (Sa) atropisomers, whose absolute configurations were respectively determined by ECD calculations. 37187248 5 14 theme bidebiline 852:861 arg1 E 863:863 bidebiline E 852:863 bidebiline E 852:863 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 5 14 theme bidebiline 852:861 arg1 Phaeanthuslucidines 823:841 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine 823:881 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine 823:881 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 5 15 theme inhibitory 904:913 arg1 activities 915:924 α-glucosidase inhibitory activities 890:924 α-glucosidase inhibitory activities 890:924 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 4 16 theme absolute 749:756 arg1 configurations 758:771 absolute configurations 749:771 absolute configurations 749:771 Phaeanthuslucidines A-C and bidebiline E were analysed and resolved by chiral HPLC to yield the (Ra) and (Sa) atropisomers, whose absolute configurations were respectively determined by ECD calculations. 37187248 2 17 theme aporphine 385:393 arg1 dimer 395:399 a C-N linked aporphine dimer 372:399 a C-N linked aporphine dimer 372:399 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 2 18 theme known 442:446 arg1 compounds 448:456 two known compounds 438:456 two known compounds 438:456 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 1 19 theme first 98:102 arg1 investigation 118:130 The first phytochemical investigation 94:130 The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. 94:171 The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. 37187248 2 20 theme linked 378:383 arg1 dimer 395:399 a C-N linked aporphine dimer 372:399 a C-N linked aporphine dimer 372:399 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 0 21 theme dimeric 25:31 arg1 derivatives 52:62 dimeric aporphine alkaloid derivatives 25:62 dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv 25:91 Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv. 37187248 0 21 theme dimeric 25:31 arg1 A-D 20:22 A-D 20:22 A-D 20:22 Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv. 37187248 1 22 theme phytochemical 104:116 arg1 investigation 118:130 The first phytochemical investigation 94:130 The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. 94:171 The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. 37187248 3 23 theme physical 582:589 arg1 data 591:594 their spectroscopic and physical data 558:594 their spectroscopic and physical data 558:594 Their structures were determined by extensive analysis of spectroscopic data, and by comparison of their spectroscopic and physical data with previous reports. 37187248 4 24 theme Phaeanthuslucidines 619:637 arg1 A-C 639:641 Phaeanthuslucidines A-C 619:641 Phaeanthuslucidines A-C 619:641 Phaeanthuslucidines A-C and bidebiline E were analysed and resolved by chiral HPLC to yield the (Ra) and (Sa) atropisomers, whose absolute configurations were respectively determined by ECD calculations. 37187248 0 25 dep Phaeanthus 69:78 arg1 lucidus 80:86 lucidus 80:86 lucidus 80:86 Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv. 37187248 3 26 theme data 531:534 arg1 analysis 505:512 extensive analysis 495:512 extensive analysis of spectroscopic data 495:534 Their structures were determined by extensive analysis of spectroscopic data, and by comparison of their spectroscopic and physical data with previous reports. 37187248 0 27 theme alkaloid 43:50 arg1 derivatives 52:62 dimeric aporphine alkaloid derivatives 25:62 dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv 25:91 Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv. 37187248 0 27 theme alkaloid 43:50 arg1 A-D 20:22 A-D 20:22 A-D 20:22 Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv. 37187248 0 28 from oliv 88:91 arg1 derivatives 52:62 dimeric aporphine alkaloid derivatives 25:62 dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv 25:91 Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv. 37187248 0 28 from oliv 88:91 arg1 A-D 20:22 A-D 20:22 A-D 20:22 Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv. 37187248 3 29 theme previous 601:608 arg1 reports 610:616 previous reports 601:616 previous reports 601:616 Their structures were determined by extensive analysis of spectroscopic data, and by comparison of their spectroscopic and physical data with previous reports. 37187248 0 30 theme aporphine 33:41 arg1 derivatives 52:62 dimeric aporphine alkaloid derivatives 25:62 dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv 25:91 Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv. 37187248 0 30 theme aporphine 33:41 arg1 A-D 20:22 A-D 20:22 A-D 20:22 Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv. 37187248 4 31 theme ECD 805:807 arg1 calculations 809:820 ECD calculations 805:820 ECD calculations 805:820 Phaeanthuslucidines A-C and bidebiline E were analysed and resolved by chiral HPLC to yield the (Ra) and (Sa) atropisomers, whose absolute configurations were respectively determined by ECD calculations. 37187248 2 32 theme phaeanthuslucidine 402:419 arg1 D 421:421 phaeanthuslucidine D 402:421 phaeanthuslucidine D 402:421 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 3 33 with comparison 544:553 arg1 reports 610:616 previous reports 601:616 previous reports 601:616 Their structures were determined by extensive analysis of spectroscopic data, and by comparison of their spectroscopic and physical data with previous reports. 37187248 2 34 theme alkaloids 238:246 arg1 identification 203:216 identification 203:216 identification 203:216 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 2 34 theme alkaloids 238:246 arg1 isolation 189:197 the isolation 185:197 the isolation 185:197 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 3 35 theme extensive 495:503 arg1 analysis 505:512 extensive analysis 495:512 extensive analysis of spectroscopic data 495:534 Their structures were determined by extensive analysis of spectroscopic data, and by comparison of their spectroscopic and physical data with previous reports. 37187248 2 36 theme undescribed 226:236 arg1 dimers 273:278 two aporphine dimers 259:278 two aporphine dimers 259:278 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 2 36 theme undescribed 226:236 arg1 alkaloids 238:246 four undescribed alkaloids 221:246 four undescribed alkaloids 221:246 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 2 37 theme phaeanthuslucidine 346:363 arg1 C 365:365 phaeanthuslucidine C 346:365 phaeanthuslucidine C 346:365 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 1 38 theme twigs 139:143 arg1 investigation 118:130 The first phytochemical investigation 94:130 The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. 94:171 The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. 37187248 2 39 link linked 378:383 arg1 dimer 395:399 a C-N linked aporphine dimer 372:399 a C-N linked aporphine dimer 372:399 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 2 40 dep linked 378:383 arg1 C-N 374:376 C-N 374:376 C-N 374:376 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 2 41 theme aristolactam-aporphine 322:343 arg1 dimer 395:399 a C-N linked aporphine dimer 372:399 a C-N linked aporphine dimer 372:399 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 2 41 theme aristolactam-aporphine 322:343 arg1 C 365:365 phaeanthuslucidine C 346:365 phaeanthuslucidine C 346:365 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 2 41 theme aristolactam-aporphine 322:343 arg1 B 307:307 B 307:307 B 307:307 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 2 41 theme aristolactam-aporphine 322:343 arg1 hybrid 312:317 a hybrid 310:317 a hybrid of aristolactam-aporphine 310:343 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 2 41 theme aristolactam-aporphine 322:343 arg1 D 421:421 phaeanthuslucidine D 402:421 phaeanthuslucidine D 402:421 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 5 42 theme IC50 931:934 arg1 values 936:941 IC50 values 931:941 IC50 values 931:941 Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 μM. 37187248 6 43 theme compounds 1050:1058 arg1 inhibition 1029:1038 α-glucosidase inhibition 1015:1038 α-glucosidase inhibition of active compounds 1015:1058 Moreover, molecular docking simulations of α-glucosidase inhibition of active compounds were studied. 37187248 2 44 theme aporphine 263:271 arg1 dimers 273:278 two aporphine dimers 259:278 two aporphine dimers 259:278 Resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. 37187248 1 45 theme Phaeanthus 148:157 arg1 Oliv 167:170 Phaeanthus lucidus Oliv 148:170 Phaeanthus lucidus Oliv 148:170 The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. 37187248 6 46 theme inhibition 1029:1038 arg1 simulations 1000:1010 molecular docking simulations 982:1010 molecular docking simulations of α-glucosidase inhibition of active compounds 982:1058 Moreover, molecular docking simulations of α-glucosidase inhibition of active compounds were studied. 37187248 0 47 theme Phaeanthus 69:78 arg1 oliv 88:91 Phaeanthus lucidus oliv 69:91 Phaeanthus lucidus oliv 69:91 Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus oliv. 37187248 1 48 theme lucidus 159:165 arg1 Oliv 167:170 Phaeanthus lucidus Oliv 148:170 Phaeanthus lucidus Oliv 148:170 The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. 37187248 6 49 theme α-glucosidase 1015:1027 arg1 inhibition 1029:1038 α-glucosidase inhibition 1015:1038 α-glucosidase inhibition of active compounds 1015:1058 Moreover, molecular docking simulations of α-glucosidase inhibition of active compounds were studied. 36986321 2 0 theme related 496:502 arg1 virus 504:508 a genetically and serologically related virus 464:508 a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV 464:590 Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. 36986321 2 0 theme related 496:502 arg1 virus 448:452 Hazara virus 441:452 Hazara virus (HAZV) 441:459 Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. 36986321 2 0 theme related 496:502 arg1 surrogate 538:546 a surrogate 536:546 a surrogate for antiviral and vaccine testing for CCHFV 536:590 Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. 36986321 0 1 theme In 196:197 arg1 Assays 215:220 In Vitro Antiviral Assays 196:220 In Vitro Antiviral Assays 196:220 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 5 2 theme iminosugars 1069:1079 arg1 inability 1022:1030 an inability 1019:1030 an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access 1019:1089 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 3 3 theme N-glycosylation 703:717 arg1 sites 719:723 two N-glycosylation sites 699:723 two N-glycosylation sites 699:723 Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. 36986321 5 4 theme oligosaccharide 1165:1179 arg1 analysis 1181:1188 free oligosaccharide analysis 1160:1188 free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells 1160:1246 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 0 5 theme Fever 84:88 arg1 Virus 90:94 Crimean-Congo Haemorrhagic Fever Virus 57:94 Crimean-Congo Haemorrhagic Fever Virus 57:94 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 3 6 theme first 670:674 arg1 time 676:679 the first time 666:679 the first time 666:679 Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. 36986321 6 7 contain have 1278:1281 arg2 potential 1283:1291 potential 1283:1291 potential as antivirals for CCHFV 1283:1315 Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation. 36986321 6 7 contain have 1278:1281 arg1 iminosugars 1258:1268 iminosugars 1258:1268 iminosugars 1258:1268 Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation. 36986321 4 8 theme titres 922:927 arg1 quantification 863:876 quantification 863:876 quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells 863:979 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 0 9 theme Antiviral 205:213 arg1 Assays 215:220 In Vitro Antiviral Assays 196:220 In Vitro Antiviral Assays 196:220 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 4 10 theme virus 916:920 arg1 titres 922:927 infectious virus titres 905:927 infectious virus titres produced following infection of SW13 and Vero cells 905:979 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 3 11 gly glycoprotein 737:748 arg1 glycoprotein 737:748 the HAZV glycoprotein 728:748 the HAZV glycoprotein 728:748 Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. 36986321 6 12 dep positions 1327:1335 arg1 the 1323:1325 the 1323:1325 the 1323:1325 Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation. 36986321 5 13 theme uninfected 1193:1202 arg1 SW13 1217:1220 uninfected and infected SW13 and uninfected Vero cells 1193:1246 SW13 1217:1220 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 0 14 theme Surrogate 107:115 arg1 Virus 124:128 the Surrogate Hazara Virus 103:128 the Surrogate Hazara Virus 103:128 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 1 15 theme causative 366:374 arg1 agent 376:380 the causative agent 362:380 the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever 362:438 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 5 16 theme Vero 1237:1240 arg1 cells 1242:1246 uninfected and infected SW13 and uninfected Vero cells 1193:1246 cells 1242:1246 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 4 17 theme total 885:889 arg1 secretion 891:899 the total secretion 881:899 the total secretion 881:899 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 5 18 theme -derivative 1057:1067 arg1 iminosugars 1069:1079 deoxynojirimycin (DNJ)-derivative iminosugars 1035:1079 deoxynojirimycin (DNJ)-derivative iminosugars 1035:1079 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 4 19 theme panel 811:815 arg1 efficacy 797:804 no apparent antiviral efficacy 775:804 no apparent antiviral efficacy of a panel of iminosugars against HAZV 775:843 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 4 20 theme SW13 961:964 arg1 cells 975:979 SW13 and Vero cells 961:979 cells 975:979 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 5 21 from analysis 1181:1188 arg1 cells 1242:1246 uninfected and infected SW13 and uninfected Vero cells 1193:1246 cells 1242:1246 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 5 21 from analysis 1181:1188 arg1 SW13 1217:1220 uninfected and infected SW13 and uninfected Vero cells 1193:1246 SW13 1217:1220 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 6 22 theme glycans 1364:1370 arg1 positions 1327:1335 positions 1327:1335 positions 1327:1335 Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation. 36986321 6 22 theme glycans 1364:1370 arg1 importance 1341:1350 importance 1341:1350 importance 1341:1350 Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation. 36986321 6 23 theme further 1427:1433 arg1 evaluation 1435:1444 further evaluation 1427:1444 further evaluation 1427:1444 Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation. 36986321 3 24 theme sites 719:723 arg1 occupation 685:694 the occupation 681:694 the occupation of two N-glycosylation sites in the HAZV glycoprotein 681:748 Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. 36986321 4 25 theme infectious 905:914 arg1 titres 922:927 infectious virus titres 905:927 infectious virus titres produced following infection of SW13 and Vero cells 905:979 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 3 26 theme HAZV 732:735 arg1 glycoprotein 737:748 the HAZV glycoprotein 728:748 the HAZV glycoprotein 728:748 Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. 36986321 4 27 theme iminosugars 820:830 arg1 panel 811:815 a panel 809:815 a panel of iminosugars 809:830 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 6 28 theme N-linked 1355:1362 arg1 glycans 1364:1370 N-linked glycans 1355:1370 N-linked glycans 1355:1370 Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation. 36986321 3 29 gly N-glycosylation 703:717 arg2 sites 719:723 two N-glycosylation sites 699:723 two N-glycosylation sites 699:723 Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. 36986321 3 29 gly N-glycosylation 703:717 arg2 two 699:701 two 699:701 two 699:701 Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. 36986321 2 30 theme antiviral 552:560 arg1 testing 574:580 antiviral and vaccine testing 552:580 testing 574:580 Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. 36986321 6 31 link N-linked 1355:1362 arg1 glycans 1364:1370 N-linked glycans 1355:1370 N-linked glycans 1355:1370 Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation. 36986321 2 32 theme Hazara 441:446 arg1 HAZV 455:458 HAZV 455:458 HAZV 455:458 Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. 36986321 2 32 theme Hazara 441:446 arg1 virus 504:508 a genetically and serologically related virus 464:508 a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV 464:590 Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. 36986321 2 32 theme Hazara 441:446 arg1 virus 448:452 Hazara virus 441:452 Hazara virus (HAZV) 441:459 Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. 36986321 1 33 theme public 298:303 arg1 concern 312:318 public health concern 298:318 public health concern 298:318 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 0 34 theme Hazara 117:122 arg1 Virus 124:128 the Surrogate Hazara Virus 103:128 the Surrogate Hazara Virus 103:128 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 4 35 theme cells 975:979 arg1 infection 948:956 infection 948:956 infection of SW13 and Vero cells 948:979 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 1 36 theme health 305:310 arg1 concern 312:318 public health concern 298:318 public health concern 298:318 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 0 37 theme Liquid-Chromatography-Based 131:157 arg1 Mapping 159:165 Liquid-Chromatography-Based Mapping 131:165 Liquid-Chromatography-Based Mapping of Viral N-Glycosylation 131:190 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 0 38 dep In 196:197 arg1 Vitro 199:203 Vitro 199:203 Vitro 199:203 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 3 39 theme Glycosylation 593:605 arg1 analysis 607:614 Glycosylation analysis 593:614 Glycosylation analysis of HAZV 593:622 Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. 36986321 1 40 theme Crimean-Congo 223:235 arg1 CCHFV 263:267 CCHFV 263:267 CCHFV 263:267 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 1 40 theme Crimean-Congo 223:235 arg1 virus 256:260 Crimean-Congo haemorrhagic fever virus 223:260 Crimean-Congo haemorrhagic fever virus (CCHFV) 223:268 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 1 40 theme Crimean-Congo 223:235 arg1 pathogen 275:282 a pathogen 273:282 a pathogen of increasing public health concern 273:318 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 0 41 theme Iminosugars 27:37 arg1 Potential 14:22 the Potential 10:22 the Potential of Iminosugars 10:37 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 5 42 theme endoplasmic 1103:1113 arg1 reticulum 1115:1123 endoplasmic reticulum 1103:1123 endoplasmic reticulum α-glucosidases 1103:1138 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 4 43 theme Vero 970:973 arg1 cells 975:979 SW13 and Vero cells 961:979 cells 975:979 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 1 44 theme fatal 401:405 arg1 fever 434:438 the potentially fatal Crimean-Congo haemorrhagic fever 385:438 the potentially fatal Crimean-Congo haemorrhagic fever 385:438 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 4 45 theme antiviral 787:795 arg1 efficacy 797:804 no apparent antiviral efficacy 775:804 no apparent antiviral efficacy of a panel of iminosugars against HAZV 775:843 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 5 46 theme free 1160:1163 arg1 analysis 1181:1188 free oligosaccharide analysis 1160:1188 free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells 1160:1246 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 1 47 theme haemorrhagic 237:248 arg1 CCHFV 263:267 CCHFV 263:267 CCHFV 263:267 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 1 47 theme haemorrhagic 237:248 arg1 virus 256:260 Crimean-Congo haemorrhagic fever virus 223:260 Crimean-Congo haemorrhagic fever virus (CCHFV) 223:268 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 1 47 theme haemorrhagic 237:248 arg1 pathogen 275:282 a pathogen 273:282 a pathogen of increasing public health concern 273:318 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 5 48 theme reticulum 1115:1123 arg1 α-glucosidases 1125:1138 endoplasmic reticulum α-glucosidases 1103:1138 endoplasmic reticulum α-glucosidases 1103:1138 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 1 49 theme Crimean-Congo 407:419 arg1 fever 434:438 the potentially fatal Crimean-Congo haemorrhagic fever 385:438 the potentially fatal Crimean-Congo haemorrhagic fever 385:438 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 5 50 theme efficacy 995:1002 arg1 lack 987:990 This lack 982:990 This lack of efficacy 982:1002 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 2 51 theme vaccine 566:572 arg1 testing 574:580 antiviral and vaccine testing 552:580 testing 574:580 Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. 36986321 3 52 from occupation 685:694 arg1 glycoprotein 737:748 the HAZV glycoprotein 728:748 the HAZV glycoprotein 728:748 Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. 36986321 4 53 theme secretion 891:899 arg1 quantification 863:876 quantification 863:876 quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells 863:979 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 1 54 theme haemorrhagic 421:432 arg1 fever 434:438 the potentially fatal Crimean-Congo haemorrhagic fever 385:438 the potentially fatal Crimean-Congo haemorrhagic fever 385:438 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 3 55 theme HAZV 619:622 arg1 analysis 607:614 Glycosylation analysis 593:614 Glycosylation analysis of HAZV 593:622 Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. 36986321 0 56 theme N-Glycosylation 176:190 arg1 Assays 215:220 In Vitro Antiviral Assays 196:220 In Vitro Antiviral Assays 196:220 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 0 56 theme N-Glycosylation 176:190 arg1 Mapping 159:165 Liquid-Chromatography-Based Mapping 131:165 Liquid-Chromatography-Based Mapping of Viral N-Glycosylation 131:190 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 1 57 theme fever 434:438 arg1 agent 376:380 the causative agent 362:380 the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever 362:438 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 1 58 theme fever 250:254 arg1 CCHFV 263:267 CCHFV 263:267 CCHFV 263:267 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 1 58 theme fever 250:254 arg1 virus 256:260 Crimean-Congo haemorrhagic fever virus 223:260 Crimean-Congo haemorrhagic fever virus (CCHFV) 223:268 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 1 58 theme fever 250:254 arg1 pathogen 275:282 a pathogen 273:282 a pathogen of increasing public health concern 273:318 Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. 36986321 0 59 theme Viral 170:174 arg1 N-Glycosylation 176:190 Viral N-Glycosylation 170:190 Viral N-Glycosylation 170:190 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 5 60 theme infected 1208:1215 arg1 SW13 1217:1220 uninfected and infected SW13 and uninfected Vero cells 1193:1246 SW13 1217:1220 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36986321 0 61 theme Haemorrhagic 71:82 arg1 Virus 90:94 Crimean-Congo Haemorrhagic Fever Virus 57:94 Crimean-Congo Haemorrhagic Fever Virus 57:94 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 4 62 theme apparent 778:785 arg1 efficacy 797:804 no apparent antiviral efficacy 775:804 no apparent antiviral efficacy of a panel of iminosugars against HAZV 775:843 Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. 36986321 0 63 theme Crimean-Congo 57:69 arg1 Virus 90:94 Crimean-Congo Haemorrhagic Fever Virus 57:94 Crimean-Congo Haemorrhagic Fever Virus 57:94 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 0 64 dep Exploring 0:8 arg1 Assays 215:220 In Vitro Antiviral Assays 196:220 In Vitro Antiviral Assays 196:220 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 0 64 dep Exploring 0:8 arg1 Mapping 159:165 Liquid-Chromatography-Based Mapping 131:165 Liquid-Chromatography-Based Mapping of Viral N-Glycosylation 131:190 Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays. 36986321 5 65 theme uninfected 1226:1235 arg1 cells 1242:1246 uninfected and infected SW13 and uninfected Vero cells 1193:1246 cells 1242:1246 This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. 36778025 7 0 theme CFTR 1593:1596 arg1 glycoisoform 1605:1616 the wild type CFTR band C glycoisoform 1579:1616 the wild type CFTR band C glycoisoform 1579:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 6 1 theme wild 1147:1150 arg1 isoform 1168:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 1 2 theme cystic 289:294 arg1 fibrosis 296:303 the progressive disease cystic fibrosis 265:303 the progressive disease cystic fibrosis 265:303 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 7 3 theme wild 1583:1586 arg1 glycoisoform 1605:1616 the wild type CFTR band C glycoisoform 1579:1616 the wild type CFTR band C glycoisoform 1579:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 7 4 theme N-linked 1526:1533 arg1 oligosaccharides 1535:1550 N-linked oligosaccharides 1526:1550 N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform 1526:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 2 5 theme molecular 316:324 arg1 therapeutics 326:337 molecular therapeutics 316:337 molecular therapeutics that improve CFTR maturation and functional defects 316:389 Recently, molecular therapeutics that improve CFTR maturation and functional defects have been approved. 36778025 8 6 theme CFTR 1802:1805 arg1 function 1783:1790 fully restored function 1768:1790 fully restored function of mutant CFTR necessary for long-term provision of clinical benefit 1768:1859 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 8 7 located observed 1711:1718 arg2 glycoisoform 1698:1709 the C* glycoisoform 1691:1709 the C* glycoisoform observed in patients' biomaterial 1691:1743 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 8 7 located observed 1711:1718 arg1 biomaterial 1733:1743 patients' biomaterial 1723:1743 patients' biomaterial 1723:1743 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 3 8 with therapy 521:527 arg1 ELX/TEZ/IVA 568:578 ELX/TEZ/IVA 568:578 ELX/TEZ/IVA 568:578 We aimed to verify whether we could detect an improvement of CFTR protein expression and maturation by triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA). 36778025 3 8 with therapy 521:527 arg1 elexacaftor-tezacaftor-ivacaftor 534:565 elexacaftor-tezacaftor-ivacaftor 534:565 elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) 534:579 We aimed to verify whether we could detect an improvement of CFTR protein expression and maturation by triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA). 36778025 6 9 theme p.Phe508el 1217:1226 arg1 protein 1233:1239 an incompletely glycosylated p.Phe508el CFTR protein 1188:1239 an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment 1188:1313 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 6 10 theme ELX/TEZ/IVA 1293:1303 arg1 treatment 1305:1313 ELX/TEZ/IVA treatment 1293:1313 ELX/TEZ/IVA treatment 1293:1313 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 2 11 theme CFTR 352:355 arg1 maturation 357:366 CFTR maturation 352:366 CFTR maturation 352:366 Recently, molecular therapeutics that improve CFTR maturation and functional defects have been approved. 36778025 1 12 theme epithelial 209:218 arg1 CFTR 242:245 the epithelial membrane glycoprotein CFTR 205:245 the epithelial membrane glycoprotein CFTR 205:245 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 6 13 dep protein 1233:1239 arg1 * 1250:1250 isoform C* 1241:1250 an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment 1188:1313 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 8 14 theme clinical 1844:1851 arg1 benefit 1853:1859 clinical benefit 1844:1859 clinical benefit 1844:1859 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 1 15 theme glycoprotein 229:240 arg1 CFTR 242:245 the epithelial membrane glycoprotein CFTR 205:245 the epithelial membrane glycoprotein CFTR 205:245 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 7 16 theme CFTR 1447:1450 arg1 processing 1426:1435 the posttranslational processing 1404:1435 the posttranslational processing of mutant CFTR 1404:1450 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 6 17 theme C 1249:1249 arg1 * 1250:1250 isoform C* 1241:1250 an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment 1188:1313 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 6 18 theme mutant 1081:1086 arg1 protein 1093:1099 the mutant CFTR protein 1077:1099 the mutant CFTR protein 1077:1099 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 4 19 theme Western 755:761 arg1 blot 763:766 CFTR Western blot 750:766 CFTR Western blot that was optimized to distinguish CFTR glycoisoforms 750:819 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 5 20 theme CFTR 832:835 arg1 analysis 856:863 CFTR western immunoblot analysis 832:863 CFTR western immunoblot analysis 832:863 Findings: CFTR western immunoblot analysis revealed that-compared to baseline-the levels of CFTR protein increased by at least twofold in eight out of 12 patients upon treatment with ELX/TEZ/IVA compared to baseline (p < 0.02). 36778025 5 21 theme CFTR 914:917 arg1 protein 919:925 CFTR protein 914:925 CFTR protein 914:925 Findings: CFTR western immunoblot analysis revealed that-compared to baseline-the levels of CFTR protein increased by at least twofold in eight out of 12 patients upon treatment with ELX/TEZ/IVA compared to baseline (p < 0.02). 36778025 5 22 theme immunoblot 845:854 arg1 analysis 856:863 CFTR western immunoblot analysis 832:863 CFTR western immunoblot analysis 832:863 Findings: CFTR western immunoblot analysis revealed that-compared to baseline-the levels of CFTR protein increased by at least twofold in eight out of 12 patients upon treatment with ELX/TEZ/IVA compared to baseline (p < 0.02). 36778025 0 23 from Changes 0:6 arg1 expression 71:80 cystic fibrosis transmembrane conductance regulator protein expression 11:80 cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy 11:141 Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy. 36778025 6 24 gly glycosylated 1134:1145 arg1 isoform 1168:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 4 25 gly glycoisoforms 807:819 arg1 CFTR 802:805 CFTR glycoisoforms 802:819 CFTR glycoisoforms 802:819 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 6 26 theme isoform 1241:1247 arg1 * 1250:1250 isoform C* 1241:1250 an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment 1188:1313 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 6 27 with patients 1255:1262 arg1 CF 1269:1270 CF 1269:1270 CF 1269:1270 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 7 28 link N-linked 1526:1533 arg1 oligosaccharides 1535:1550 N-linked oligosaccharides 1526:1550 N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform 1526:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 3 29 theme CFTR 472:475 arg1 expression 485:494 CFTR protein expression 472:494 CFTR protein expression 472:494 We aimed to verify whether we could detect an improvement of CFTR protein expression and maturation by triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA). 36778025 1 30 from Defects 156:162 arg1 function 193:200 function 193:200 function 193:200 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 1 30 from Defects 156:162 arg1 maturation 179:188 maturation 179:188 maturation 179:188 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 1 30 from Defects 156:162 arg1 expression 167:176 expression 167:176 expression 167:176 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 8 31 gly glycosylation 1674:1686 arg1 glycoisoform 1698:1709 the C* glycoisoform 1691:1709 the C* glycoisoform observed in patients' biomaterial 1691:1743 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 3 32 theme maturation 500:509 arg1 improvement 457:467 an improvement 454:467 an improvement of CFTR protein expression and maturation by triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) 454:579 We aimed to verify whether we could detect an improvement of CFTR protein expression and maturation by triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA). 36778025 0 33 theme cystic 11:16 arg1 regulator 53:61 cystic fibrosis transmembrane conductance regulator 11:61 cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy 11:141 Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy. 36778025 3 34 theme expression 485:494 arg1 improvement 457:467 an improvement 454:467 an improvement of CFTR protein expression and maturation by triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) 454:579 We aimed to verify whether we could detect an improvement of CFTR protein expression and maturation by triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA). 36778025 0 35 theme transmembrane 27:39 arg1 regulator 53:61 cystic fibrosis transmembrane conductance regulator 11:61 cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy 11:141 Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy. 36778025 6 36 theme protein 1093:1099 arg1 polydispersity 1059:1072 polydispersity 1059:1072 polydispersity of the mutant CFTR protein 1059:1099 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 8 37 theme immature 1665:1672 arg1 glycosylation 1674:1686 immature glycosylation 1665:1686 immature glycosylation 1665:1686 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 0 38 theme regulator 53:61 arg1 expression 71:80 cystic fibrosis transmembrane conductance regulator protein expression 11:80 cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy 11:141 Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy. 36778025 7 39 with Treatment 1332:1340 arg1 ELX/TEZ/IVA 1347:1357 ELX/TEZ/IVA 1347:1357 ELX/TEZ/IVA 1347:1357 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 8 40 theme * 1696:1696 arg1 glycoisoform 1698:1709 the C* glycoisoform 1691:1709 the C* glycoisoform observed in patients' biomaterial 1691:1743 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 4 41 theme Rectal 591:596 arg1 biopsies 606:613 Rectal suction biopsies 591:613 Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA 591:731 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 4 42 with treatment 706:714 arg1 ELX/TEZ/IVA 721:731 ELX/TEZ/IVA 721:731 ELX/TEZ/IVA 721:731 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 2 43 theme functional 372:381 arg1 defects 383:389 functional defects 372:389 functional defects 372:389 Recently, molecular therapeutics that improve CFTR maturation and functional defects have been approved. 36778025 7 44 theme band 1598:1601 arg1 glycoisoform 1605:1616 the wild type CFTR band C glycoisoform 1579:1616 the wild type CFTR band C glycoisoform 1579:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 6 45 theme Golgi 1162:1166 arg1 isoform 1168:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 4 46 theme CF 669:670 arg1 patients 672:679 21 p.Phe508del homozygous or compound heterozygous CF patients 618:679 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA 618:731 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 7 47 theme protein 1369:1375 arg1 expression 1377:1386 protein expression 1369:1386 protein expression 1369:1386 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 7 48 theme type 1588:1591 arg1 glycoisoform 1605:1616 the wild type CFTR band C glycoisoform 1579:1616 the wild type CFTR band C glycoisoform 1579:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 6 49 theme type 1152:1155 arg1 isoform 1168:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 8 50 theme glycoisoform 1698:1709 arg1 amounts 1654:1660 lower amounts 1648:1660 lower amounts 1648:1660 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 8 50 theme glycoisoform 1698:1709 arg1 glycosylation 1674:1686 immature glycosylation 1665:1686 immature glycosylation 1665:1686 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 8 50 theme glycoisoform 1698:1709 arg1 glycoisoform 1698:1709 the C* glycoisoform 1691:1709 the C* glycoisoform observed in patients' biomaterial 1691:1743 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 1 51 theme disease 281:287 arg1 fibrosis 296:303 the progressive disease cystic fibrosis 265:303 the progressive disease cystic fibrosis 265:303 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 6 52 theme glycosylated 1134:1145 arg1 isoform 1168:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 4 53 theme homozygous 633:642 arg1 patients 672:679 21 p.Phe508del homozygous or compound heterozygous CF patients 618:679 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA 618:731 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 7 54 theme oligosaccharides 1535:1550 arg1 spectrum 1514:1521 the polydisperse spectrum 1497:1521 the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform 1497:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 4 55 theme compound 647:654 arg1 patients 672:679 21 p.Phe508del homozygous or compound heterozygous CF patients 618:679 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA 618:731 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 1 56 gly glycoprotein 229:240 arg1 glycoprotein 229:240 the epithelial membrane glycoprotein CFTR 205:245 the epithelial membrane glycoprotein CFTR 205:245 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 8 57 theme mutant 1795:1800 arg1 CFTR 1802:1805 mutant CFTR 1795:1805 mutant CFTR 1795:1805 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 6 58 theme CFTR 1228:1231 arg1 protein 1233:1239 an incompletely glycosylated p.Phe508el CFTR protein 1188:1239 an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment 1188:1313 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 6 59 gly glycosylated 1204:1215 arg1 protein 1233:1239 an incompletely glycosylated p.Phe508el CFTR protein 1188:1239 an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment 1188:1313 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 8 60 theme necessary 1807:1815 arg1 function 1783:1790 fully restored function 1768:1790 fully restored function of mutant CFTR necessary for long-term provision of clinical benefit 1768:1859 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 6 61 theme glycosylated 1204:1215 arg1 protein 1233:1239 an incompletely glycosylated p.Phe508el CFTR protein 1188:1239 an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment 1188:1313 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 8 62 theme long-term 1821:1829 arg1 provision 1831:1839 long-term provision 1821:1839 long-term provision of clinical benefit 1821:1859 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 5 63 theme protein 919:925 arg1 levels 904:909 baseline-the levels 891:909 baseline-the levels of CFTR protein 891:925 Findings: CFTR western immunoblot analysis revealed that-compared to baseline-the levels of CFTR protein increased by at least twofold in eight out of 12 patients upon treatment with ELX/TEZ/IVA compared to baseline (p < 0.02). 36778025 7 64 theme polydisperse 1501:1512 arg1 spectrum 1514:1521 the polydisperse spectrum 1497:1521 the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform 1497:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 1 65 theme CFTR 242:245 arg1 function 193:200 function 193:200 function 193:200 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 1 65 theme CFTR 242:245 arg1 maturation 179:188 maturation 179:188 maturation 179:188 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 1 65 theme CFTR 242:245 arg1 expression 167:176 expression 167:176 expression 167:176 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 4 66 dep homozygous 633:642 arg1 heterozygous 656:667 heterozygous 656:667 heterozygous 656:667 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 8 67 theme benefit 1853:1859 arg1 provision 1831:1839 long-term provision 1821:1839 long-term provision of clinical benefit 1821:1859 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 8 68 dep amounts 1654:1660 arg1 the 1644:1646 the 1644:1646 the 1644:1646 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 7 69 gly glycoisoform 1605:1616 arg1 band 1598:1601 the wild type CFTR band C glycoisoform 1579:1616 the wild type CFTR band C glycoisoform 1579:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 7 69 gly glycoisoform 1605:1616 arg1 type 1588:1591 the wild type CFTR band C glycoisoform 1579:1616 the wild type CFTR band C glycoisoform 1579:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 7 69 gly glycoisoform 1605:1616 arg1 C 1603:1603 the wild type CFTR band C glycoisoform 1579:1616 the wild type CFTR band C glycoisoform 1579:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 7 69 gly glycoisoform 1605:1616 arg1 CFTR 1593:1596 the wild type CFTR band C glycoisoform 1579:1616 the wild type CFTR band C glycoisoform 1579:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 6 70 theme CFTR 1088:1091 arg1 protein 1093:1099 the mutant CFTR protein 1077:1099 the mutant CFTR protein 1077:1099 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 3 71 theme triple 514:519 arg1 therapy 521:527 triple therapy 514:527 triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) 514:579 We aimed to verify whether we could detect an improvement of CFTR protein expression and maturation by triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA). 36778025 1 72 theme membrane 220:227 arg1 CFTR 242:245 the epithelial membrane glycoprotein CFTR 205:245 the epithelial membrane glycoprotein CFTR 205:245 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36778025 7 73 theme mutant 1440:1445 arg1 CFTR 1447:1450 mutant CFTR 1440:1450 mutant CFTR 1440:1450 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 4 74 theme CFTR 750:753 arg1 blot 763:766 CFTR Western blot 750:766 CFTR Western blot that was optimized to distinguish CFTR glycoisoforms 750:819 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 5 75 theme western 837:843 arg1 analysis 856:863 CFTR western immunoblot analysis 832:863 CFTR western immunoblot analysis 832:863 Findings: CFTR western immunoblot analysis revealed that-compared to baseline-the levels of CFTR protein increased by at least twofold in eight out of 12 patients upon treatment with ELX/TEZ/IVA compared to baseline (p < 0.02). 36778025 0 76 theme elexacaftor-tezacaftor-ivacaftor 102:133 arg1 therapy 135:141 elexacaftor-tezacaftor-ivacaftor therapy 102:141 elexacaftor-tezacaftor-ivacaftor therapy 102:141 Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy. 36778025 5 77 theme p 1039:1039 arg1 baseline 1029:1036 baseline 1029:1036 baseline (p < 0.02) 1029:1047 Findings: CFTR western immunoblot analysis revealed that-compared to baseline-the levels of CFTR protein increased by at least twofold in eight out of 12 patients upon treatment with ELX/TEZ/IVA compared to baseline (p < 0.02). 36778025 5 77 theme p 1039:1039 arg1 < 1041:1041 p < 0.02 1039:1046 p < 0.02 1039:1046 Findings: CFTR western immunoblot analysis revealed that-compared to baseline-the levels of CFTR protein increased by at least twofold in eight out of 12 patients upon treatment with ELX/TEZ/IVA compared to baseline (p < 0.02). 36778025 6 78 from protein 1233:1239 arg1 patients 1255:1262 patients 1255:1262 patients with CF 1255:1270 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 7 79 theme posttranslational 1408:1424 arg1 processing 1426:1435 the posttranslational processing 1404:1435 the posttranslational processing of mutant CFTR 1404:1450 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 8 80 theme C 1695:1695 arg1 glycoisoform 1698:1709 the C* glycoisoform 1691:1709 the C* glycoisoform observed in patients' biomaterial 1691:1743 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 3 81 theme protein 477:483 arg1 expression 485:494 CFTR protein expression 472:494 CFTR protein expression 472:494 We aimed to verify whether we could detect an improvement of CFTR protein expression and maturation by triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA). 36778025 5 82 theme baseline-the 891:902 arg1 levels 904:909 baseline-the levels 891:909 baseline-the levels of CFTR protein 891:925 Findings: CFTR western immunoblot analysis revealed that-compared to baseline-the levels of CFTR protein increased by at least twofold in eight out of 12 patients upon treatment with ELX/TEZ/IVA compared to baseline (p < 0.02). 36778025 8 83 theme lower 1648:1652 arg1 amounts 1654:1660 lower amounts 1648:1660 lower amounts 1648:1660 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 8 83 theme lower 1648:1652 arg1 glycoisoform 1698:1709 the C* glycoisoform 1691:1709 the C* glycoisoform observed in patients' biomaterial 1691:1743 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 5 84 with treatment 990:998 arg1 ELX/TEZ/IVA 1005:1015 ELX/TEZ/IVA 1005:1015 ELX/TEZ/IVA 1005:1015 Findings: CFTR western immunoblot analysis revealed that-compared to baseline-the levels of CFTR protein increased by at least twofold in eight out of 12 patients upon treatment with ELX/TEZ/IVA compared to baseline (p < 0.02). 36778025 4 85 theme CFTR 802:805 arg1 glycoisoforms 807:819 CFTR glycoisoforms 802:819 CFTR glycoisoforms 802:819 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 0 86 theme fibrosis 18:25 arg1 regulator 53:61 cystic fibrosis transmembrane conductance regulator 11:61 cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy 11:141 Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy. 36778025 0 87 dep prior 82:86 arg1 to 88:89 to 88:89 to 88:89 Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy. 36778025 4 88 theme p.Phe508del 621:631 arg1 patients 672:679 21 p.Phe508del homozygous or compound heterozygous CF patients 618:679 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA 618:731 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 0 89 theme conductance 41:51 arg1 regulator 53:61 cystic fibrosis transmembrane conductance regulator 11:61 cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy 11:141 Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy. 36778025 0 90 theme protein 63:69 arg1 expression 71:80 cystic fibrosis transmembrane conductance regulator protein expression 11:80 cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy 11:141 Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy. 36778025 8 91 gly glycoisoform 1698:1709 arg1 C 1695:1695 the C* glycoisoform 1691:1709 the C* glycoisoform observed in patients' biomaterial 1691:1743 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 8 91 gly glycoisoform 1698:1709 arg1 * 1696:1696 the C* glycoisoform 1691:1709 the C* glycoisoform observed in patients' biomaterial 1691:1743 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 4 92 theme suction 598:604 arg1 biopsies 606:613 Rectal suction biopsies 591:613 Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA 591:731 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 4 93 theme patients 672:679 arg1 biopsies 606:613 Rectal suction biopsies 591:613 Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA 591:731 Methods: Rectal suction biopsies of 21 p.Phe508del homozygous or compound heterozygous CF patients obtained pre- and during treatment with ELX/TEZ/IVA were analyzed by CFTR Western blot that was optimized to distinguish CFTR glycoisoforms. 36778025 7 94 theme C 1603:1603 arg1 glycoisoform 1605:1616 the wild type CFTR band C glycoisoform 1579:1616 the wild type CFTR band C glycoisoform 1579:1616 Interpretation: Treatment with ELX/TEZ/IVA increased protein expression by facilitating the posttranslational processing of mutant CFTR but apparently did not succeed in generating the polydisperse spectrum of N-linked oligosaccharides that is characteristic for the wild type CFTR band C glycoisoform. 36778025 6 95 theme CFTR 1157:1160 arg1 isoform 1168:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 the fully glycosylated wild type CFTR Golgi isoform 1124:1174 However, polydispersity of the mutant CFTR protein was lower than that of the fully glycosylated wild type CFTR Golgi isoform, indicating an incompletely glycosylated p.Phe508el CFTR protein isoform C* in patients with CF which persists after ELX/TEZ/IVA treatment. 36778025 8 96 theme restored 1774:1781 arg1 function 1783:1790 fully restored function 1768:1790 fully restored function of mutant CFTR necessary for long-term provision of clinical benefit 1768:1859 Our results caution that the lower amounts or immature glycosylation of the C* glycoisoform observed in patients' biomaterial might not translate to fully restored function of mutant CFTR necessary for long-term provision of clinical benefit. 36778025 1 97 theme progressive 269:279 arg1 fibrosis 296:303 the progressive disease cystic fibrosis 265:303 the progressive disease cystic fibrosis 265:303 Background: Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. 36772828 0 0 theme epithelial 79:88 arg1 plasticity 90:99 epithelial plasticity 79:99 epithelial plasticity 79:99 Genomic targets of the IRE1-XBP1s pathway in mediating metabolic adaptation in epithelial plasticity. 36772828 7 1 dep factors 1035:1041 arg1 factors 1035:1041 core mesenchymal transcription factors SNAI1 and ZEB1 1004:1056 core mesenchymal transcription factors SNAI1 and ZEB1 1004:1056 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 1 dep factors 1035:1041 arg1 ZEB1 1053:1056 ZEB1 1053:1056 ZEB1 1053:1056 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 1 dep factors 1035:1041 arg1 SNAI1 1043:1047 SNAI1 1043:1047 SNAI1 1043:1047 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 2 theme hexosamine 1076:1085 arg1 HBP 1109:1111 HBP 1109:1111 HBP 1109:1111 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 2 theme hexosamine 1076:1085 arg1 pathway 1100:1106 hexosamine biosynthetic pathway 1076:1106 hexosamine biosynthetic pathway (HBP) enzymes 1076:1120 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 1 3 theme complex 147:153 arg1 plasticity 125:134 Epithelial mesenchymal plasticity 102:134 Epithelial mesenchymal plasticity (EMP) 102:140 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 1 3 theme complex 147:153 arg1 event 178:182 a complex cellular reprogramming event 145:182 a complex cellular reprogramming event that plays a major role in tissue homeostasis 145:228 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 9 4 theme transcription 1416:1428 arg1 factors 1430:1436 mesenchymal transcription factors 1404:1436 mesenchymal transcription factors 1404:1436 We conclude that the IRE1α-XBP1s pathway coordinately regulates mesenchymal transcription factors and hexosamine biosynthesis in EMP by a mechanism involving recruitment of activated pSer2-Pol II to GC-rich promoters. 36772828 7 5 theme biosynthetic 1087:1098 arg1 HBP 1109:1111 HBP 1109:1111 HBP 1109:1111 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 5 theme biosynthetic 1087:1098 arg1 pathway 1100:1106 hexosamine biosynthetic pathway 1076:1106 hexosamine biosynthetic pathway (HBP) enzymes 1076:1120 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 1 6 theme cellular 155:162 arg1 plasticity 125:134 Epithelial mesenchymal plasticity 102:134 Epithelial mesenchymal plasticity (EMP) 102:140 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 1 6 theme cellular 155:162 arg1 event 178:182 a complex cellular reprogramming event 145:182 a complex cellular reprogramming event that plays a major role in tissue homeostasis 145:228 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 6 7 theme sites 956:960 arg1 kb 930:931 1 kb 928:931 1 kb of transcription start sites of 2119 promoters 928:978 Strikingly, XBP1s peaks were within 1 kb of transcription start sites of 2119 promoters. 36772828 7 8 theme XBP1s 1158:1162 arg1 peaks 1164:1168 proximal XBP1s peaks 1149:1168 proximal XBP1s peaks 1149:1168 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 9 9 theme hexosamine 1442:1451 arg1 biosynthesis 1453:1464 hexosamine biosynthesis 1442:1464 hexosamine biosynthesis in EMP 1442:1471 We conclude that the IRE1α-XBP1s pathway coordinately regulates mesenchymal transcription factors and hexosamine biosynthesis in EMP by a mechanism involving recruitment of activated pSer2-Pol II to GC-rich promoters. 36772828 4 10 theme AP-1 724:727 arg1 motifs 729:734 AP-1 motifs 724:734 AP-1 motifs 724:734 CUT&RUN identified 7086 binding sites in chromatin that were enriched in AP-1 motifs and GC-sequences. 36772828 6 11 theme start 950:954 arg1 sites 956:960 transcription start sites 936:960 transcription start sites of 2119 promoters 936:978 Strikingly, XBP1s peaks were within 1 kb of transcription start sites of 2119 promoters. 36772828 6 11 theme start 950:954 arg1 promoters 970:978 2119 promoters 965:978 2119 promoters 965:978 Strikingly, XBP1s peaks were within 1 kb of transcription start sites of 2119 promoters. 36772828 9 12 theme activated 1513:1521 arg1 pSer2-Pol 1523:1531 activated pSer2-Pol II 1513:1534 activated pSer2-Pol II 1513:1534 We conclude that the IRE1α-XBP1s pathway coordinately regulates mesenchymal transcription factors and hexosamine biosynthesis in EMP by a mechanism involving recruitment of activated pSer2-Pol II to GC-rich promoters. 36772828 8 13 theme modified 1319:1326 arg1 Pol 1332:1334 modified RNA Pol II 1319:1337 elongation-competent phospho-Ser2 CTD modified RNA Pol II 1281:1337 We demonstrate that IRE1α -XBP1s signaling is necessary and sufficient to activate core enzymes by recruiting elongation-competent phospho-Ser2 CTD modified RNA Pol II. 36772828 2 14 theme IRE1α 343:347 arg1 protein 364:370 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 309:372 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis 309:393 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 6 15 theme transcription 936:948 arg1 sites 956:960 transcription start sites 936:960 transcription start sites of 2119 promoters 936:978 Strikingly, XBP1s peaks were within 1 kb of transcription start sites of 2119 promoters. 36772828 6 15 theme transcription 936:948 arg1 promoters 970:978 2119 promoters 965:978 2119 promoters 965:978 Strikingly, XBP1s peaks were within 1 kb of transcription start sites of 2119 promoters. 36772828 7 16 dep binding 996:1002 arg1 addition 984:991 addition 984:991 addition 984:991 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 5 17 theme ER-Golgi 872:879 arg1 transport 881:889 ER-Golgi transport 872:889 ER-Golgi transport 872:889 Of these binding sites, XBP1s peaks mapped to 4827 genes controlling Rho-GTPase signaling, N-linked glycosylation and ER-Golgi transport. 36772828 3 18 from Nuclease 583:590 arg1 infection 640:648 RSV infection 636:648 RSV infection 636:648 To better understand the genomic targets of XBP1s, we identified its genomic targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection. 36772828 1 19 theme reprogramming 164:176 arg1 plasticity 125:134 Epithelial mesenchymal plasticity 102:134 Epithelial mesenchymal plasticity (EMP) 102:140 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 1 19 theme reprogramming 164:176 arg1 event 178:182 a complex cellular reprogramming event 145:182 a complex cellular reprogramming event that plays a major role in tissue homeostasis 145:228 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 7 20 theme proximal 1149:1156 arg1 peaks 1164:1168 proximal XBP1s peaks 1149:1168 proximal XBP1s peaks 1149:1168 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 9 21 theme mesenchymal 1404:1414 arg1 factors 1430:1436 mesenchymal transcription factors 1404:1436 mesenchymal transcription factors 1404:1436 We conclude that the IRE1α-XBP1s pathway coordinately regulates mesenchymal transcription factors and hexosamine biosynthesis in EMP by a mechanism involving recruitment of activated pSer2-Pol II to GC-rich promoters. 36772828 8 22 theme core 1254:1257 arg1 enzymes 1259:1265 core enzymes 1254:1265 core enzymes 1254:1265 We demonstrate that IRE1α -XBP1s signaling is necessary and sufficient to activate core enzymes by recruiting elongation-competent phospho-Ser2 CTD modified RNA Pol II. 36772828 2 23 theme protein 265:271 arg1 UPR 283:285 UPR 283:285 UPR 283:285 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 2 23 theme protein 265:271 arg1 response 273:280 the unfolded protein response 252:280 the unfolded protein response (UPR) 252:286 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 2 24 theme spliced 374:380 arg1 axis 390:393 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis 309:393 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis 309:393 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 5 25 theme binding 763:769 arg1 sites 771:775 these binding sites 757:775 these binding sites 757:775 Of these binding sites, XBP1s peaks mapped to 4827 genes controlling Rho-GTPase signaling, N-linked glycosylation and ER-Golgi transport. 36772828 5 26 theme Rho-GTPase 823:832 arg1 signaling 834:842 Rho-GTPase signaling 823:842 Rho-GTPase signaling 823:842 Of these binding sites, XBP1s peaks mapped to 4827 genes controlling Rho-GTPase signaling, N-linked glycosylation and ER-Golgi transport. 36772828 0 27 theme Genomic 0:6 arg1 targets 8:14 Genomic targets 0:14 Genomic targets of the IRE1-XBP1s pathway in mediating metabolic adaptation in epithelial plasticity. 0:100 Genomic targets of the IRE1-XBP1s pathway in mediating metabolic adaptation in epithelial plasticity. 36772828 8 28 theme -XBP1s 1197:1202 arg1 signaling 1204:1212 IRE1α -XBP1s signaling 1191:1212 IRE1α -XBP1s signaling 1191:1212 We demonstrate that IRE1α -XBP1s signaling is necessary and sufficient to activate core enzymes by recruiting elongation-competent phospho-Ser2 CTD modified RNA Pol II. 36772828 7 29 theme transcription 1021:1033 arg1 factors 1035:1041 core mesenchymal transcription factors SNAI1 and ZEB1 1004:1056 core mesenchymal transcription factors SNAI1 and ZEB1 1004:1056 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 29 theme transcription 1021:1033 arg1 ZEB1 1053:1056 ZEB1 1053:1056 ZEB1 1053:1056 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 29 theme transcription 1021:1033 arg1 SNAI1 1043:1047 SNAI1 1043:1047 SNAI1 1043:1047 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 2 30 theme protein 364:370 arg1 axis 390:393 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis 309:393 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis 309:393 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 2 31 theme glucose 406:412 arg1 shunting 414:421 glucose shunting 406:421 glucose shunting to protein N glycosylation 406:448 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 1 32 theme Epithelial 102:111 arg1 EMP 137:139 EMP 137:139 EMP 137:139 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 1 32 theme Epithelial 102:111 arg1 plasticity 125:134 Epithelial mesenchymal plasticity 102:134 Epithelial mesenchymal plasticity (EMP) 102:140 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 1 32 theme Epithelial 102:111 arg1 event 178:182 a complex cellular reprogramming event 145:182 a complex cellular reprogramming event that plays a major role in tissue homeostasis 145:228 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 8 33 dep CTD 1315:1317 arg1 Pol 1332:1334 modified RNA Pol II 1319:1337 elongation-competent phospho-Ser2 CTD modified RNA Pol II 1281:1337 We demonstrate that IRE1α -XBP1s signaling is necessary and sufficient to activate core enzymes by recruiting elongation-competent phospho-Ser2 CTD modified RNA Pol II. 36772828 5 34 theme XBP1s 778:782 arg1 peaks 784:788 XBP1s peaks 778:788 XBP1s peaks 778:788 Of these binding sites, XBP1s peaks mapped to 4827 genes controlling Rho-GTPase signaling, N-linked glycosylation and ER-Golgi transport. 36772828 9 35 from factors 1430:1436 arg1 EMP 1469:1471 EMP 1469:1471 EMP 1469:1471 We conclude that the IRE1α-XBP1s pathway coordinately regulates mesenchymal transcription factors and hexosamine biosynthesis in EMP by a mechanism involving recruitment of activated pSer2-Pol II to GC-rich promoters. 36772828 1 36 theme mesenchymal 113:123 arg1 EMP 137:139 EMP 137:139 EMP 137:139 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 1 36 theme mesenchymal 113:123 arg1 plasticity 125:134 Epithelial mesenchymal plasticity 102:134 Epithelial mesenchymal plasticity (EMP) 102:140 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 1 36 theme mesenchymal 113:123 arg1 event 178:182 a complex cellular reprogramming event 145:182 a complex cellular reprogramming event that plays a major role in tissue homeostasis 145:228 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 9 37 theme GC-rich 1539:1545 arg1 promoters 1547:1555 GC-rich promoters 1539:1555 GC-rich promoters 1539:1555 We conclude that the IRE1α-XBP1s pathway coordinately regulates mesenchymal transcription factors and hexosamine biosynthesis in EMP by a mechanism involving recruitment of activated pSer2-Pol II to GC-rich promoters. 36772828 1 38 theme major 197:201 arg1 role 203:206 a major role 195:206 a major role 195:206 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 0 39 theme pathway 34:40 arg1 targets 8:14 Genomic targets 0:14 Genomic targets of the IRE1-XBP1s pathway in mediating metabolic adaptation in epithelial plasticity. 0:100 Genomic targets of the IRE1-XBP1s pathway in mediating metabolic adaptation in epithelial plasticity. 36772828 8 40 theme phospho-Ser2 1302:1313 arg1 CTD 1315:1317 elongation-competent phospho-Ser2 CTD modified RNA Pol II 1281:1337 elongation-competent phospho-Ser2 CTD modified RNA Pol II 1281:1337 We demonstrate that IRE1α -XBP1s signaling is necessary and sufficient to activate core enzymes by recruiting elongation-competent phospho-Ser2 CTD modified RNA Pol II. 36772828 7 41 theme mesenchymal 1009:1019 arg1 factors 1035:1041 core mesenchymal transcription factors SNAI1 and ZEB1 1004:1056 core mesenchymal transcription factors SNAI1 and ZEB1 1004:1056 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 41 theme mesenchymal 1009:1019 arg1 ZEB1 1053:1056 ZEB1 1053:1056 ZEB1 1053:1056 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 41 theme mesenchymal 1009:1019 arg1 SNAI1 1043:1047 SNAI1 1043:1047 SNAI1 1043:1047 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 3 42 theme FLAG-epitope 607:618 arg1 XBP1s 627:631 a FLAG-epitope tagged XBP1s 605:631 a FLAG-epitope tagged XBP1s 605:631 To better understand the genomic targets of XBP1s, we identified its genomic targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection. 36772828 8 43 theme elongation-competent 1281:1300 arg1 CTD 1315:1317 elongation-competent phospho-Ser2 CTD modified RNA Pol II 1281:1337 elongation-competent phospho-Ser2 CTD modified RNA Pol II 1281:1337 We demonstrate that IRE1α -XBP1s signaling is necessary and sufficient to activate core enzymes by recruiting elongation-competent phospho-Ser2 CTD modified RNA Pol II. 36772828 7 44 theme pathway 1100:1106 arg1 enzymes 1114:1120 hexosamine biosynthetic pathway (HBP) enzymes 1076:1120 hexosamine biosynthetic pathway (HBP) enzymes 1076:1120 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 0 45 theme IRE1-XBP1s 23:32 arg1 pathway 34:40 the IRE1-XBP1s pathway 19:40 the IRE1-XBP1s pathway 19:40 Genomic targets of the IRE1-XBP1s pathway in mediating metabolic adaptation in epithelial plasticity. 36772828 5 46 link N-linked 845:852 arg1 glycosylation 854:866 N-linked glycosylation 845:866 N-linked glycosylation 845:866 Of these binding sites, XBP1s peaks mapped to 4827 genes controlling Rho-GTPase signaling, N-linked glycosylation and ER-Golgi transport. 36772828 0 47 from adaptation 65:74 arg1 plasticity 90:99 epithelial plasticity 79:99 epithelial plasticity 79:99 Genomic targets of the IRE1-XBP1s pathway in mediating metabolic adaptation in epithelial plasticity. 36772828 5 48 theme 4827 800:803 arg1 genes 805:809 4827 genes 800:809 4827 genes controlling Rho-GTPase signaling, N-linked glycosylation and ER-Golgi transport 800:889 Of these binding sites, XBP1s peaks mapped to 4827 genes controlling Rho-GTPase signaling, N-linked glycosylation and ER-Golgi transport. 36772828 2 49 theme N 434:434 arg1 glycosylation 436:448 protein N glycosylation 426:448 protein N glycosylation 426:448 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 3 50 theme genomic 476:482 arg1 targets 484:490 the genomic targets 472:490 the genomic targets of XBP1s 472:499 To better understand the genomic targets of XBP1s, we identified its genomic targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection. 36772828 4 51 theme binding 675:681 arg1 sites 683:687 7086 binding sites 670:687 7086 binding sites in chromatin that were enriched in AP-1 motifs and GC-sequences 670:751 CUT&RUN identified 7086 binding sites in chromatin that were enriched in AP-1 motifs and GC-sequences. 36772828 2 52 theme protein 426:432 arg1 glycosylation 436:448 protein N glycosylation 426:448 protein N glycosylation 426:448 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 6 53 theme XBP1s 904:908 arg1 peaks 910:914 XBP1s peaks 904:914 XBP1s peaks 904:914 Strikingly, XBP1s peaks were within 1 kb of transcription start sites of 2119 promoters. 36772828 7 54 theme core 1004:1007 arg1 factors 1035:1041 core mesenchymal transcription factors SNAI1 and ZEB1 1004:1056 core mesenchymal transcription factors SNAI1 and ZEB1 1004:1056 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 54 theme core 1004:1007 arg1 ZEB1 1053:1056 ZEB1 1053:1056 ZEB1 1053:1056 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 7 54 theme core 1004:1007 arg1 SNAI1 1043:1047 SNAI1 1043:1047 SNAI1 1043:1047 In addition to binding core mesenchymal transcription factors SNAI1 and ZEB1, we observed that hexosamine biosynthetic pathway (HBP) enzymes were induced and contained proximal XBP1s peaks. 36772828 2 55 theme protein 332:338 arg1 protein 364:370 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 309:372 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis 309:393 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 3 56 theme RSV 636:638 arg1 infection 640:648 RSV infection 636:648 RSV infection 636:648 To better understand the genomic targets of XBP1s, we identified its genomic targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection. 36772828 2 57 theme unfolded 256:263 arg1 UPR 283:285 UPR 283:285 UPR 283:285 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 2 57 theme unfolded 256:263 arg1 response 273:280 the unfolded protein response 252:280 the unfolded protein response (UPR) 252:286 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 2 58 theme inositol-requiring 313:330 arg1 protein 364:370 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 309:372 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis 309:393 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 3 59 theme genomic 520:526 arg1 targets 528:534 its genomic targets 516:534 its genomic targets using Cleavage Under Targets and Release 516:575 To better understand the genomic targets of XBP1s, we identified its genomic targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection. 36772828 1 60 theme tissue 211:216 arg1 homeostasis 218:228 tissue homeostasis 211:228 tissue homeostasis 211:228 Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. 36772828 3 61 theme tagged 620:625 arg1 XBP1s 627:631 a FLAG-epitope tagged XBP1s 605:631 a FLAG-epitope tagged XBP1s 605:631 To better understand the genomic targets of XBP1s, we identified its genomic targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection. 36772828 8 62 theme RNA 1328:1330 arg1 Pol 1332:1334 modified RNA Pol II 1319:1337 elongation-competent phospho-Ser2 CTD modified RNA Pol II 1281:1337 We demonstrate that IRE1α -XBP1s signaling is necessary and sufficient to activate core enzymes by recruiting elongation-competent phospho-Ser2 CTD modified RNA Pol II. 36772828 9 63 from biosynthesis 1453:1464 arg1 EMP 1469:1471 EMP 1469:1471 EMP 1469:1471 We conclude that the IRE1α-XBP1s pathway coordinately regulates mesenchymal transcription factors and hexosamine biosynthesis in EMP by a mechanism involving recruitment of activated pSer2-Pol II to GC-rich promoters. 36772828 5 64 theme N-linked 845:852 arg1 glycosylation 854:866 N-linked glycosylation 845:866 N-linked glycosylation 845:866 Of these binding sites, XBP1s peaks mapped to 4827 genes controlling Rho-GTPase signaling, N-linked glycosylation and ER-Golgi transport. 36772828 9 65 theme IRE1α-XBP1s 1361:1371 arg1 pathway 1373:1379 the IRE1α-XBP1s pathway 1357:1379 the IRE1α-XBP1s pathway 1357:1379 We conclude that the IRE1α-XBP1s pathway coordinately regulates mesenchymal transcription factors and hexosamine biosynthesis in EMP by a mechanism involving recruitment of activated pSer2-Pol II to GC-rich promoters. 36772828 3 66 theme XBP1s 627:631 arg1 Nuclease 583:590 Nuclease 583:590 Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection 583:648 To better understand the genomic targets of XBP1s, we identified its genomic targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection. 36772828 3 66 theme XBP1s 627:631 arg1 CUT&RUN 593:599 CUT&RUN 593:599 CUT&RUN 593:599 To better understand the genomic targets of XBP1s, we identified its genomic targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection. 36772828 9 67 theme pSer2-Pol 1523:1531 arg1 recruitment 1498:1508 recruitment 1498:1508 recruitment of activated pSer2-Pol II to GC-rich promoters 1498:1555 We conclude that the IRE1α-XBP1s pathway coordinately regulates mesenchymal transcription factors and hexosamine biosynthesis in EMP by a mechanism involving recruitment of activated pSer2-Pol II to GC-rich promoters. 36772828 2 68 theme -X-box-binding 349:362 arg1 protein 364:370 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 309:372 the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis 309:393 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 4 69 from sites 683:687 arg1 chromatin 692:700 chromatin 692:700 chromatin 692:700 CUT&RUN identified 7086 binding sites in chromatin that were enriched in AP-1 motifs and GC-sequences. 36772828 6 70 theme promoters 970:978 arg1 sites 956:960 transcription start sites 936:960 transcription start sites of 2119 promoters 936:978 Strikingly, XBP1s peaks were within 1 kb of transcription start sites of 2119 promoters. 36772828 6 70 theme promoters 970:978 arg1 promoters 970:978 2119 promoters 965:978 2119 promoters 965:978 Strikingly, XBP1s peaks were within 1 kb of transcription start sites of 2119 promoters. 36772828 0 71 theme metabolic 55:63 arg1 adaptation 65:74 metabolic adaptation 55:74 metabolic adaptation in epithelial plasticity 55:99 Genomic targets of the IRE1-XBP1s pathway in mediating metabolic adaptation in epithelial plasticity. 36772828 8 72 theme IRE1α 1191:1195 arg1 signaling 1204:1212 IRE1α -XBP1s signaling 1191:1212 IRE1α -XBP1s signaling 1191:1212 We demonstrate that IRE1α -XBP1s signaling is necessary and sufficient to activate core enzymes by recruiting elongation-competent phospho-Ser2 CTD modified RNA Pol II. 36772828 2 73 dep spliced 374:380 arg1 XBP1s 383:387 XBP1s 383:387 XBP1s 383:387 Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. 36772828 3 74 theme XBP1s 495:499 arg1 targets 484:490 the genomic targets 472:490 the genomic targets of XBP1s 472:499 To better understand the genomic targets of XBP1s, we identified its genomic targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection. 36772828 6 75 theme 2119 965:968 arg1 promoters 970:978 2119 promoters 965:978 2119 promoters 965:978 Strikingly, XBP1s peaks were within 1 kb of transcription start sites of 2119 promoters. 36634851 6 0 theme genetic 1239:1245 arg1 strains 1247:1253 genetic strains 1239:1253 genetic strains with different levels of POMT activity 1239:1292 Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. 36634851 1 1 theme muscular 248:255 arg1 dystrophies 257:267 congenital muscular dystrophies 237:267 congenital muscular dystrophies 237:267 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 7 2 theme POMTs 1458:1462 arg1 expression 1444:1453 expression 1444:1453 expression of POMTs 1444:1462 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 6 3 theme glycoproteomic 1121:1134 arg1 approaches 1136:1145 glycoproteomic approaches 1121:1145 glycoproteomic approaches 1121:1145 Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. 36634851 9 4 theme neurological 1865:1876 arg1 defects 1878:1884 neurological defects 1865:1884 neurological defects in muscular dystrophies 1865:1908 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 7 5 from mutants 1509:1515 arg1 absent 1494:1499 absent 1494:1499 absent 1494:1499 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 4 6 theme PTP69D 812:817 arg1 alleles 771:777 mutant alleles 764:777 mutant alleles 764:777 Using RNAi-mediated knockdown, mutant alleles, and a dominant-negative form of PTP69D, we reveal that PTP69D is required for the wiring of larval sensory axons. 36634851 4 6 theme PTP69D 812:817 arg1 form 804:807 a dominant-negative form 784:807 a dominant-negative form of PTP69D 784:817 Using RNAi-mediated knockdown, mutant alleles, and a dominant-negative form of PTP69D, we reveal that PTP69D is required for the wiring of larval sensory axons. 36634851 4 6 theme PTP69D 812:817 arg1 knockdown 753:761 RNAi-mediated knockdown 739:761 RNAi-mediated knockdown 739:761 Using RNAi-mediated knockdown, mutant alleles, and a dominant-negative form of PTP69D, we reveal that PTP69D is required for the wiring of larval sensory axons. 36634851 3 7 theme POMT 677:680 arg1 genes 682:686 POMT genes 677:686 POMT genes 677:686 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 1 8 theme congenital 237:246 arg1 dystrophies 257:267 congenital muscular dystrophies 237:267 congenital muscular dystrophies 237:267 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 1 9 theme Protein 163:169 arg1 O-Mannosyltransferases 171:192 Protein O-Mannosyltransferases 163:192 Protein O-Mannosyltransferases (POMTs) 163:200 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 1 9 theme Protein 163:169 arg1 POMTs 195:199 POMTs 195:199 POMTs 195:199 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 3 10 theme rotation 713:720 arg1 phenotype 722:730 the abdomen rotation phenotype 701:730 the abdomen rotation phenotype 701:730 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 8 11 theme axon 1701:1704 arg1 connectivity 1706:1717 axon connectivity 1701:1717 axon connectivity 1701:1717 Taken together, our results indicate that PTP69D is a novel functional substrate of POMTs that is required for axon connectivity. 36634851 4 12 theme larval 872:877 arg1 axons 887:891 larval sensory axons 872:891 larval sensory axons 872:891 Using RNAi-mediated knockdown, mutant alleles, and a dominant-negative form of PTP69D, we reveal that PTP69D is required for the wiring of larval sensory axons. 36634851 7 13 theme hexose 1352:1357 arg1 modifications 1359:1371 many O-linked hexose modifications 1338:1371 many O-linked hexose modifications 1338:1371 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 5 14 theme complex 997:1003 arg1 effects 1033:1039 complex synergistic or antagonistic effects 997:1039 complex synergistic or antagonistic effects on axon wiring phenotypes 997:1065 We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. 36634851 4 15 theme axons 887:891 arg1 wiring 862:867 the wiring 858:867 the wiring of larval sensory axons 858:891 Using RNAi-mediated knockdown, mutant alleles, and a dominant-negative form of PTP69D, we reveal that PTP69D is required for the wiring of larval sensory axons. 36634851 7 16 theme many 1338:1341 arg1 modifications 1359:1371 many O-linked hexose modifications 1338:1371 many O-linked hexose modifications 1338:1371 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 0 17 theme sensory 121:127 arg1 axons 129:133 sensory axons 121:133 sensory axons 121:133 Protein Tyrosine Phosphatase 69D is a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila. 36634851 3 18 theme mutants 577:583 arg1 phenotypes 558:567 the phenotypes 554:567 the phenotypes of POMT mutants 554:583 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 3 19 theme Receptor 599:606 arg1 Phosphatase 625:635 Receptor Protein Tyrosine Phosphatase 69D 599:639 Receptor Protein Tyrosine Phosphatase 69D (PTP69D) 599:648 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 3 19 theme Receptor 599:606 arg1 PTP69D 642:647 PTP69D 642:647 PTP69D 642:647 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 3 19 theme Receptor 599:606 arg1 gene 655:658 a gene 653:658 a gene interacting with POMT genes in producing the abdomen rotation phenotype 653:730 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 7 20 theme POMT-mediated 1559:1571 arg1 O-mannosylation 1573:1587 POMT-mediated O-mannosylation 1559:1587 POMT-mediated O-mannosylation 1559:1587 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 9 21 from defects 1878:1884 arg1 dystrophies 1898:1908 muscular dystrophies 1889:1908 muscular dystrophies 1889:1908 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 0 22 theme Protein 51:57 arg1 O-Mannosyltransferases 59:80 Protein O-Mannosyltransferases 1-2 51:84 Protein O-Mannosyltransferases 1-2 51:84 Protein Tyrosine Phosphatase 69D is a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila. 36634851 9 23 theme regulation 1752:1761 arg1 mechanism 1725:1733 This mechanism 1720:1733 This mechanism of POMT-mediated regulation of RPTP functions 1720:1779 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 7 24 theme PTP69D 1313:1318 arg1 construct 1320:1328 the PTP69D construct 1309:1328 the PTP69D construct 1309:1328 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 0 25 theme axons 129:133 arg1 wiring 111:116 the wiring 107:116 the wiring of sensory axons in Drosophila 107:147 Protein Tyrosine Phosphatase 69D is a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila. 36634851 5 26 theme PTP69D 913:918 arg1 genes 929:933 PTP69D and POMT genes 913:933 PTP69D and POMT genes 913:933 We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. 36634851 9 27 theme RPTP 1766:1769 arg1 functions 1771:1779 RPTP functions 1766:1779 RPTP functions 1766:1779 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 5 28 theme axon 1044:1047 arg1 phenotypes 1056:1065 axon wiring phenotypes 1044:1065 axon wiring phenotypes 1044:1065 We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. 36634851 5 29 theme POMT 924:927 arg1 genes 929:933 PTP69D and POMT genes 913:933 PTP69D and POMT genes 913:933 We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. 36634851 2 30 theme other 448:452 arg1 POMTs 442:446 POMTs 442:446 POMTs other than α-Dg 442:462 However, neurological phenotypes of POMT mutants are not well understood, and the functional substrates of POMTs other than α-Dg remain unknown. 36634851 0 31 theme Protein 0:6 arg1 Phosphatase 17:27 Protein Tyrosine Phosphatase 0:27 Protein Tyrosine Phosphatase 69D 0:31 Protein Tyrosine Phosphatase 69D is a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila. 36634851 5 32 theme manipulation 1101:1112 arg1 mode 1085:1088 the mode 1081:1088 the mode of genetic manipulation 1081:1112 We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. 36634851 2 33 theme functional 417:426 arg1 substrates 428:437 the functional substrates 413:437 the functional substrates of POMTs other than α-Dg 413:462 However, neurological phenotypes of POMT mutants are not well understood, and the functional substrates of POMTs other than α-Dg remain unknown. 36634851 0 34 theme Phosphatase 17:27 arg1 69D 29:31 Protein Tyrosine Phosphatase 69D 0:31 Protein Tyrosine Phosphatase 69D 0:31 Protein Tyrosine Phosphatase 69D is a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila. 36634851 0 34 theme Phosphatase 17:27 arg1 substrate 38:46 a substrate 36:46 a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila 36:147 Protein Tyrosine Phosphatase 69D is a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila. 36634851 1 35 theme α-Dystroglycan 312:325 arg1 glycosylation 295:307 abnormal glycosylation 286:307 abnormal glycosylation of α-Dystroglycan (α-Dg) 286:332 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 3 36 theme Tyrosine 616:623 arg1 Phosphatase 625:635 Receptor Protein Tyrosine Phosphatase 69D 599:639 Receptor Protein Tyrosine Phosphatase 69D (PTP69D) 599:648 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 3 36 theme Tyrosine 616:623 arg1 PTP69D 642:647 PTP69D 642:647 PTP69D 642:647 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 3 36 theme Tyrosine 616:623 arg1 gene 655:658 a gene 653:658 a gene interacting with POMT genes in producing the abdomen rotation phenotype 653:730 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 2 37 theme neurological 344:355 arg1 phenotypes 357:366 neurological phenotypes 344:366 neurological phenotypes of POMT mutants 344:382 However, neurological phenotypes of POMT mutants are not well understood, and the functional substrates of POMTs other than α-Dg remain unknown. 36634851 6 38 theme transgenic 1205:1214 arg1 construct 1216:1224 the PTP69D transgenic construct 1194:1224 the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity 1194:1292 Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. 36634851 4 39 theme mutant 764:769 arg1 alleles 771:777 mutant alleles 764:777 mutant alleles 764:777 Using RNAi-mediated knockdown, mutant alleles, and a dominant-negative form of PTP69D, we reveal that PTP69D is required for the wiring of larval sensory axons. 36634851 1 40 theme severe 212:217 arg1 defects 225:231 severe brain defects 212:231 severe brain defects 212:231 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 2 41 theme mutants 376:382 arg1 phenotypes 357:366 neurological phenotypes 344:366 neurological phenotypes of POMT mutants 344:382 However, neurological phenotypes of POMT mutants are not well understood, and the functional substrates of POMTs other than α-Dg remain unknown. 36634851 0 42 from wiring 111:116 arg1 Drosophila 138:147 Drosophila 138:147 Drosophila 138:147 Protein Tyrosine Phosphatase 69D is a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila. 36634851 8 43 theme novel 1644:1648 arg1 substrate 1661:1669 a novel functional substrate 1642:1669 a novel functional substrate of POMTs that is required for axon connectivity 1642:1717 Taken together, our results indicate that PTP69D is a novel functional substrate of POMTs that is required for axon connectivity. 36634851 8 43 theme novel 1644:1648 arg1 PTP69D 1632:1637 PTP69D 1632:1637 PTP69D 1632:1637 Taken together, our results indicate that PTP69D is a novel functional substrate of POMTs that is required for axon connectivity. 36634851 7 44 contain carries 1330:1336 arg2 modifications 1359:1371 many O-linked hexose modifications 1338:1371 many O-linked hexose modifications 1338:1371 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 7 44 contain carries 1330:1336 arg1 construct 1320:1328 the PTP69D construct 1309:1328 the PTP69D construct 1309:1328 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 7 45 from absent 1494:1499 arg1 mutants 1509:1515 POMT mutants 1504:1515 POMT mutants 1504:1515 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 6 46 gly glycosylation 1177:1189 arg1 construct 1216:1224 the PTP69D transgenic construct 1194:1224 the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity 1194:1292 Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. 36634851 9 47 theme defects 1878:1884 arg1 etiology 1853:1860 the etiology 1849:1860 the etiology of neurological defects in muscular dystrophies 1849:1908 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 6 48 theme construct 1216:1224 arg1 glycosylation 1177:1189 the glycosylation 1173:1189 the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity 1173:1292 Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. 36634851 8 49 theme POMTs 1674:1678 arg1 substrate 1661:1669 a novel functional substrate 1642:1669 a novel functional substrate of POMTs that is required for axon connectivity 1642:1717 Taken together, our results indicate that PTP69D is a novel functional substrate of POMTs that is required for axon connectivity. 36634851 8 49 theme POMTs 1674:1678 arg1 PTP69D 1632:1637 PTP69D 1632:1637 PTP69D 1632:1637 Taken together, our results indicate that PTP69D is a novel functional substrate of POMTs that is required for axon connectivity. 36634851 9 50 from etiology 1853:1860 arg1 dystrophies 1898:1908 muscular dystrophies 1889:1908 muscular dystrophies 1889:1908 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 9 51 theme muscular 1889:1896 arg1 dystrophies 1898:1908 muscular dystrophies 1889:1908 muscular dystrophies 1889:1908 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 6 52 theme PTP69D 1198:1203 arg1 construct 1216:1224 the PTP69D transgenic construct 1194:1224 the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity 1194:1292 Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. 36634851 3 53 theme abdomen 705:711 arg1 phenotype 722:730 the abdomen rotation phenotype 701:730 the abdomen rotation phenotype 701:730 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 6 54 theme activity 1285:1292 arg1 levels 1270:1275 different levels 1260:1275 different levels of POMT activity 1260:1292 Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. 36634851 5 55 theme synergistic 1005:1015 arg1 effects 1033:1039 complex synergistic or antagonistic effects 997:1039 complex synergistic or antagonistic effects on axon wiring phenotypes 997:1065 We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. 36634851 3 56 theme POMT 572:575 arg1 mutants 577:583 POMT mutants 572:583 POMT mutants 572:583 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 4 57 theme sensory 879:885 arg1 axons 887:891 larval sensory axons 872:891 larval sensory axons 872:891 Using RNAi-mediated knockdown, mutant alleles, and a dominant-negative form of PTP69D, we reveal that PTP69D is required for the wiring of larval sensory axons. 36634851 7 58 theme O-linked 1343:1350 arg1 modifications 1359:1371 many O-linked hexose modifications 1338:1371 many O-linked hexose modifications 1338:1371 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 5 59 theme antagonistic 1020:1031 arg1 effects 1033:1039 complex synergistic or antagonistic effects 997:1039 complex synergistic or antagonistic effects on axon wiring phenotypes 997:1065 We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. 36634851 7 60 theme O-mannosylation 1573:1587 arg1 PTP69D 1534:1539 PTP69D 1534:1539 PTP69D 1534:1539 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 7 60 theme O-mannosylation 1573:1587 arg1 substrate 1546:1554 a substrate 1544:1554 a substrate of POMT-mediated O-mannosylation 1544:1587 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 6 61 theme different 1260:1268 arg1 levels 1270:1275 different levels 1260:1275 different levels of POMT activity 1260:1292 Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. 36634851 1 62 gly glycosylation 295:307 arg1 α-Dg 328:331 α-Dg 328:331 α-Dg 328:331 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 1 62 gly glycosylation 295:307 arg1 α-Dystroglycan 312:325 α-Dystroglycan 312:325 α-Dystroglycan (α-Dg) 312:332 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 9 63 from dystrophies 1898:1908 arg1 etiology 1853:1860 the etiology 1849:1860 the etiology of neurological defects in muscular dystrophies 1849:1908 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 0 64 theme O-Mannosyltransferases 59:80 arg1 69D 29:31 Protein Tyrosine Phosphatase 69D 0:31 Protein Tyrosine Phosphatase 69D 0:31 Protein Tyrosine Phosphatase 69D is a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila. 36634851 0 64 theme O-Mannosyltransferases 59:80 arg1 substrate 38:46 a substrate 36:46 a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila 36:147 Protein Tyrosine Phosphatase 69D is a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila. 36634851 9 65 theme POMT-mediated 1738:1750 arg1 regulation 1752:1761 POMT-mediated regulation 1738:1761 POMT-mediated regulation of RPTP functions 1738:1779 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 1 66 from Mutations 150:158 arg1 O-Mannosyltransferases 171:192 Protein O-Mannosyltransferases 163:192 Protein O-Mannosyltransferases (POMTs) 163:200 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 1 66 from Mutations 150:158 arg1 POMTs 195:199 POMTs 195:199 POMTs 195:199 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 9 67 theme functions 1771:1779 arg1 regulation 1752:1761 POMT-mediated regulation 1738:1761 POMT-mediated regulation of RPTP functions 1738:1779 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 4 68 theme RNAi-mediated 739:751 arg1 knockdown 753:761 RNAi-mediated knockdown 739:761 RNAi-mediated knockdown 739:761 Using RNAi-mediated knockdown, mutant alleles, and a dominant-negative form of PTP69D, we reveal that PTP69D is required for the wiring of larval sensory axons. 36634851 0 69 theme Tyrosine 8:15 arg1 Phosphatase 17:27 Protein Tyrosine Phosphatase 0:27 Protein Tyrosine Phosphatase 69D 0:31 Protein Tyrosine Phosphatase 69D is a substrate of Protein O-Mannosyltransferases 1-2 that is required for the wiring of sensory axons in Drosophila. 36634851 5 70 theme wiring 1049:1054 arg1 phenotypes 1056:1065 axon wiring phenotypes 1044:1065 axon wiring phenotypes 1044:1065 We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. 36634851 2 71 theme POMTs 442:446 arg1 substrates 428:437 the functional substrates 413:437 the functional substrates of POMTs other than α-Dg 413:462 However, neurological phenotypes of POMT mutants are not well understood, and the functional substrates of POMTs other than α-Dg remain unknown. 36634851 5 72 from effects 1033:1039 arg1 phenotypes 1056:1065 axon wiring phenotypes 1044:1065 axon wiring phenotypes 1044:1065 We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. 36634851 1 73 theme abnormal 286:293 arg1 glycosylation 295:307 abnormal glycosylation 286:307 abnormal glycosylation of α-Dystroglycan (α-Dg) 286:332 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 3 74 theme Protein 608:614 arg1 Phosphatase 625:635 Receptor Protein Tyrosine Phosphatase 69D 599:639 Receptor Protein Tyrosine Phosphatase 69D (PTP69D) 599:648 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 3 74 theme Protein 608:614 arg1 PTP69D 642:647 PTP69D 642:647 PTP69D 642:647 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 3 74 theme Protein 608:614 arg1 gene 655:658 a gene 653:658 a gene interacting with POMT genes in producing the abdomen rotation phenotype 653:730 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 7 75 theme POMT 1504:1507 arg1 mutants 1509:1515 POMT mutants 1504:1515 POMT mutants 1504:1515 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 7 76 link O-linked 1343:1350 arg1 modifications 1359:1371 many O-linked hexose modifications 1338:1371 many O-linked hexose modifications 1338:1371 We found that the PTP69D construct carries many O-linked hexose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs, but these modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. 36634851 4 77 theme dominant-negative 786:802 arg1 form 804:807 a dominant-negative form 784:807 a dominant-negative form of PTP69D 784:817 Using RNAi-mediated knockdown, mutant alleles, and a dominant-negative form of PTP69D, we reveal that PTP69D is required for the wiring of larval sensory axons. 36634851 3 78 theme Drosophila 488:497 arg1 model 499:503 a Drosophila model 486:503 a Drosophila model 486:503 Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Receptor Protein Tyrosine Phosphatase 69D (PTP69D) as a gene interacting with POMT genes in producing the abdomen rotation phenotype. 36634851 5 79 theme genetic 1093:1099 arg1 manipulation 1101:1112 genetic manipulation 1093:1112 genetic manipulation 1093:1112 We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. 36634851 9 80 theme new 1836:1838 arg1 light 1840:1844 new light 1836:1844 new light 1836:1844 This mechanism of POMT-mediated regulation of RPTP functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies. 36634851 6 81 theme POMT 1280:1283 arg1 activity 1285:1292 POMT activity 1280:1292 POMT activity 1280:1292 Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. 36634851 6 82 with strains 1247:1253 arg1 levels 1270:1275 different levels 1260:1275 different levels of POMT activity 1260:1292 Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. 36634851 1 83 theme brain 219:223 arg1 defects 225:231 severe brain defects 212:231 severe brain defects 212:231 Mutations in Protein O-Mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-Dystroglycan (α-Dg). 36634851 2 84 theme POMT 371:374 arg1 mutants 376:382 POMT mutants 371:382 POMT mutants 371:382 However, neurological phenotypes of POMT mutants are not well understood, and the functional substrates of POMTs other than α-Dg remain unknown. 36634851 8 85 theme functional 1650:1659 arg1 substrate 1661:1669 a novel functional substrate 1642:1669 a novel functional substrate of POMTs that is required for axon connectivity 1642:1717 Taken together, our results indicate that PTP69D is a novel functional substrate of POMTs that is required for axon connectivity. 36634851 8 85 theme functional 1650:1659 arg1 PTP69D 1632:1637 PTP69D 1632:1637 PTP69D 1632:1637 Taken together, our results indicate that PTP69D is a novel functional substrate of POMTs that is required for axon connectivity. 35167946 3 0 theme modification 491:502 arg1 importance 472:481 The importance 468:481 The importance of this modification for function of TSR-proteins 468:531 The importance of this modification for function of TSR-proteins is underscored by the early embryonic lethality of mouse embryos lacking Pofut2. 35167946 9 1 theme other 1568:1572 arg1 substrates 1581:1590 two other POFUT2 substrates 1564:1590 two other POFUT2 substrates important for bone development, ADAMTS6 and 10, 1564:1638 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 6 2 theme decreased 1214:1222 arg1 BMP 1224:1226 decreased BMP and IHH signaling 1214:1244 BMP 1224:1226 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 35167946 3 3 theme TSR-proteins 520:531 arg1 function 508:515 function 508:515 function of TSR-proteins 508:531 The importance of this modification for function of TSR-proteins is underscored by the early embryonic lethality of mouse embryos lacking Pofut2. 35167946 7 4 theme hypertrophic 1345:1356 arg1 zone 1358:1361 the hypertrophic zone 1341:1361 the hypertrophic zone 1341:1361 Consistent with these changes we saw a decrease in the size of the hypertrophic zone with lower levels of Collagen-X. 35167946 7 5 with Consistent 1278:1287 arg1 changes 1300:1306 these changes 1294:1306 these changes 1294:1306 Consistent with these changes we saw a decrease in the size of the hypertrophic zone with lower levels of Collagen-X. 35167946 3 6 theme embryonic 561:569 arg1 lethality 571:579 the early embryonic lethality 551:579 the early embryonic lethality of mouse embryos lacking Pofut2 551:611 The importance of this modification for function of TSR-proteins is underscored by the early embryonic lethality of mouse embryos lacking Pofut2. 35167946 1 7 theme ECM 186:188 arg1 properties 190:199 ECM properties 186:199 ECM properties 186:199 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 4 8 theme early 626:630 arg1 lethality 632:640 early lethality 626:640 early lethality 626:640 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 11 9 theme POFUT2 1948:1953 arg1 substrates 1955:1964 POFUT2 substrates 1948:1964 POFUT2 substrates 1948:1964 In addition, these observations raise the possibility that the O-fucose modification on TSRs extends beyond promoting efficient trafficking of POFUT2 substrates and has the potential to influence their function in the extracellular environment. 35167946 1 10 theme Many 119:122 arg1 proteins 162:169 Many extracellular matrix (ECM) associated proteins 119:169 Many extracellular matrix (ECM) associated proteins that influence ECM properties 119:199 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 5 11 theme ADAMTS 1061:1066 arg1 proteins 1079:1086 ADAMTS or ADAMTSL proteins 1061:1086 proteins 1079:1086 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 3 12 theme embryos 590:596 arg1 lethality 571:579 the early embryonic lethality 551:579 the early embryonic lethality of mouse embryos lacking Pofut2 551:611 The importance of this modification for function of TSR-proteins is underscored by the early embryonic lethality of mouse embryos lacking Pofut2. 35167946 1 13 theme type 221:224 arg1 TSRs 237:240 TSRs 237:240 TSRs 237:240 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 1 13 theme type 221:224 arg1 repeats 228:234 Thrombospondin type 1 repeats 206:234 Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose 206:281 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 6 14 theme TGF-β 1261:1265 arg1 signaling 1267:1275 increased TGF-β signaling 1251:1275 increased TGF-β signaling 1251:1275 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 35167946 5 15 theme significant 904:914 arg1 shortening 916:925 significant shortening 904:925 significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins 904:1086 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 4 16 theme POFUT2 712:717 arg1 substrates 719:728 POFUT2 substrates 712:728 POFUT2 substrates 712:728 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 4 17 from Pofut2 789:794 arg1 mesenchyme 819:828 the developing limb mesenchyme 799:828 the developing limb mesenchyme 799:828 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 1 18 theme matrix 138:143 arg1 proteins 162:169 Many extracellular matrix (ECM) associated proteins 119:169 Many extracellular matrix (ECM) associated proteins that influence ECM properties 119:199 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 11 19 theme extracellular 2023:2035 arg1 environment 2037:2047 the extracellular environment 2019:2047 the extracellular environment 2019:2047 In addition, these observations raise the possibility that the O-fucose modification on TSRs extends beyond promoting efficient trafficking of POFUT2 substrates and has the potential to influence their function in the extracellular environment. 35167946 8 20 theme minimal 1422:1428 arg1 effects 1430:1436 minimal effects 1422:1436 minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone 1422:1539 Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. 35167946 4 21 theme Pofut2 676:681 arg1 impact 662:667 the impact 658:667 the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo 658:775 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 11 22 from function 2007:2014 arg1 environment 2037:2047 the extracellular environment 2019:2047 the extracellular environment 2019:2047 In addition, these observations raise the possibility that the O-fucose modification on TSRs extends beyond promoting efficient trafficking of POFUT2 substrates and has the potential to influence their function in the extracellular environment. 35167946 4 23 dep in 769:770 arg1 vivo 772:775 vivo 772:775 vivo 772:775 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 1 24 theme associated 151:160 arg1 proteins 162:169 Many extracellular matrix (ECM) associated proteins 119:169 Many extracellular matrix (ECM) associated proteins that influence ECM properties 119:199 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 9 25 theme POFUT2-null 1676:1686 arg1 cells 1696:1700 POFUT2-null HEK293T cells 1676:1700 POFUT2-null HEK293T cells 1676:1700 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 8 26 theme Pofut2 1445:1450 arg1 effects 1430:1436 minimal effects 1422:1436 minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone 1422:1539 Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. 35167946 5 27 theme ADAMTSL 1071:1077 arg1 proteins 1079:1086 ADAMTS or ADAMTSL proteins 1061:1086 proteins 1079:1086 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 0 28 theme bone 101:104 arg1 development 106:116 bone development 101:116 bone development 101:116 O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development. 35167946 2 29 theme enzyme 357:362 arg1 POFUT2 396:401 POFUT2 396:401 POFUT2 396:401 The O-fucose is added in the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) and is proposed to promote efficient trafficking of substrates. 35167946 2 29 theme enzyme 357:362 arg1 O-fucosyltransferase-2 372:393 the enzyme Protein O-fucosyltransferase-2 353:393 the enzyme Protein O-fucosyltransferase-2 (POFUT2) 353:402 The O-fucose is added in the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) and is proposed to promote efficient trafficking of substrates. 35167946 5 30 theme limbs 934:938 arg1 shortening 916:925 significant shortening 904:925 significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins 904:1086 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 7 31 from decrease 1317:1324 arg1 size 1333:1336 the size 1329:1336 the size of the hypertrophic zone with lower levels of Collagen-X 1329:1393 Consistent with these changes we saw a decrease in the size of the hypertrophic zone with lower levels of Collagen-X. 35167946 8 32 theme POFUT2 1481:1486 arg1 ADAMTS17 1508:1515 ADAMTS17 1508:1515 ADAMTS17 1508:1515 Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. 35167946 8 32 theme POFUT2 1481:1486 arg1 CCN2 1500:1503 CCN2 1500:1503 CCN2 1500:1503 Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. 35167946 8 32 theme POFUT2 1481:1486 arg1 substrates 1488:1497 two POFUT2 substrates 1477:1497 two POFUT2 substrates 1477:1497 Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. 35167946 4 33 theme extracellular 737:749 arg1 properties 758:767 extracellular matrix properties 737:767 extracellular matrix properties in vivo 737:775 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 0 34 gly O-fucosylation 0:13 arg1 repeats 40:46 thrombospondin type 1 repeats 18:46 thrombospondin type 1 repeats 18:46 O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development. 35167946 0 34 gly O-fucosylation 0:13 arg1 ECM 65:67 ECM remodeling 65:78 ECM remodeling 65:78 O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development. 35167946 0 35 theme thrombospondin 18:31 arg1 repeats 40:46 thrombospondin type 1 repeats 18:46 thrombospondin type 1 repeats 18:46 O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development. 35167946 9 36 from cells 1696:1700 arg1 secretion 1661:1669 secretion 1661:1669 secretion from POFUT2-null HEK293T cells 1661:1700 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 9 36 from cells 1696:1700 arg1 decrease 1649:1656 a decrease 1647:1656 a decrease in secretion from POFUT2-null HEK293T cells 1647:1700 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 5 37 theme long 941:944 arg1 bones 946:950 long bones 941:950 long bones 941:950 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 2 38 theme substrates 456:465 arg1 trafficking 441:451 efficient trafficking 431:451 efficient trafficking of substrates 431:465 The O-fucose is added in the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) and is proposed to promote efficient trafficking of substrates. 35167946 4 39 theme limb 814:817 arg1 mesenchyme 819:828 the developing limb mesenchyme 799:828 the developing limb mesenchyme 799:828 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 9 40 from decrease 1649:1656 arg1 secretion 1661:1669 secretion 1661:1669 secretion from POFUT2-null HEK293T cells 1661:1700 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 9 40 from decrease 1649:1656 arg1 cells 1696:1700 POFUT2-null HEK293T cells 1676:1700 POFUT2-null HEK293T cells 1676:1700 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 1 41 theme ECM 146:148 arg1 proteins 162:169 Many extracellular matrix (ECM) associated proteins 119:169 Many extracellular matrix (ECM) associated proteins that influence ECM properties 119:199 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 10 42 theme mutation 1773:1780 arg1 impact 1752:1757 the impact 1748:1757 the impact of the Pofut2 mutation 1748:1780 These combined results suggest that the impact of the Pofut2 mutation is cell-type specific. 35167946 10 42 theme mutation 1773:1780 arg1 specific 1795:1802 specific 1795:1802 specific 1795:1802 These combined results suggest that the impact of the Pofut2 mutation is cell-type specific. 35167946 1 43 link O-linked 267:274 arg1 fucose 276:281 O-linked fucose 267:281 O-linked fucose 267:281 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 2 44 theme folded 338:343 arg1 TSRs 345:348 folded TSRs 338:348 folded TSRs 338:348 The O-fucose is added in the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) and is proposed to promote efficient trafficking of substrates. 35167946 6 45 theme IHH 1232:1234 arg1 signaling 1236:1244 decreased BMP and IHH signaling 1214:1244 signaling 1236:1244 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 35167946 11 46 theme efficient 1923:1931 arg1 trafficking 1933:1943 efficient trafficking 1923:1943 efficient trafficking of POFUT2 substrates 1923:1964 In addition, these observations raise the possibility that the O-fucose modification on TSRs extends beyond promoting efficient trafficking of POFUT2 substrates and has the potential to influence their function in the extracellular environment. 35167946 11 47 theme substrates 1955:1964 arg1 trafficking 1933:1943 efficient trafficking 1923:1943 efficient trafficking of POFUT2 substrates 1923:1964 In addition, these observations raise the possibility that the O-fucose modification on TSRs extends beyond promoting efficient trafficking of POFUT2 substrates and has the potential to influence their function in the extracellular environment. 35167946 9 48 theme POFUT2 1574:1579 arg1 substrates 1581:1590 two other POFUT2 substrates 1564:1590 two other POFUT2 substrates important for bone development, ADAMTS6 and 10, 1564:1638 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 6 49 theme O-fucosylation 1153:1166 arg1 loss 1145:1148 loss 1145:1148 loss of O-fucosylation 1145:1166 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 35167946 11 50 from modification 1877:1888 arg1 TSRs 1893:1896 TSRs 1893:1896 TSRs 1893:1896 In addition, these observations raise the possibility that the O-fucose modification on TSRs extends beyond promoting efficient trafficking of POFUT2 substrates and has the potential to influence their function in the extracellular environment. 35167946 6 51 theme BMP 1224:1226 arg1 accumulation 1178:1189 an accumulation 1175:1189 an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling 1175:1275 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 35167946 4 52 from impact 662:667 arg1 properties 758:767 extracellular matrix properties 737:767 extracellular matrix properties in vivo 737:775 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 4 52 from impact 662:667 arg1 secretion 699:707 the secretion 695:707 the secretion of POFUT2 substrates 695:728 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 7 53 theme Collagen-X 1384:1393 arg1 levels 1374:1379 lower levels 1368:1379 lower levels of Collagen-X 1368:1393 Consistent with these changes we saw a decrease in the size of the hypertrophic zone with lower levels of Collagen-X. 35167946 9 54 theme important 1592:1600 arg1 substrates 1581:1590 two other POFUT2 substrates 1564:1590 two other POFUT2 substrates important for bone development, ADAMTS6 and 10, 1564:1638 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 7 55 theme lower 1368:1372 arg1 levels 1374:1379 lower levels 1368:1379 lower levels of Collagen-X 1368:1393 Consistent with these changes we saw a decrease in the size of the hypertrophic zone with lower levels of Collagen-X. 35167946 3 56 theme early 555:559 arg1 lethality 571:579 the early embryonic lethality 551:579 the early embryonic lethality of mouse embryos lacking Pofut2 551:611 The importance of this modification for function of TSR-proteins is underscored by the early embryonic lethality of mouse embryos lacking Pofut2. 35167946 4 57 theme Prrx1-Cre 836:844 arg1 recombinase 846:856 Prrx1-Cre recombinase 836:856 Prrx1-Cre recombinase 836:856 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 7 58 theme zone 1358:1361 arg1 size 1333:1336 the size 1329:1336 the size of the hypertrophic zone with lower levels of Collagen-X 1329:1393 Consistent with these changes we saw a decrease in the size of the hypertrophic zone with lower levels of Collagen-X. 35167946 6 59 theme embryonic 1120:1128 arg1 day 1130:1132 embryonic day 14.5 1120:1137 embryonic day 14.5 1120:1137 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 35167946 9 60 theme bone 1606:1609 arg1 ADAMTS6 1624:1630 ADAMTS6 1624:1630 ADAMTS6 1624:1630 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 9 60 theme bone 1606:1609 arg1 development 1611:1621 bone development 1606:1621 bone development 1606:1621 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 9 60 theme bone 1606:1609 arg1 10 1636:1637 10 1636:1637 10 1636:1637 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 3 61 theme mouse 584:588 arg1 embryos 590:596 mouse embryos 584:596 mouse embryos lacking Pofut2 584:611 The importance of this modification for function of TSR-proteins is underscored by the early embryonic lethality of mouse embryos lacking Pofut2. 35167946 5 62 from dysplasias 1011:1020 arg1 mice 1038:1041 mice 1038:1041 mice with mutations in ADAMTS or ADAMTSL proteins 1038:1086 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 5 62 from dysplasias 1011:1020 arg1 human 1025:1029 human 1025:1029 human 1025:1029 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 7 63 dep saw 1311:1313 arg1 Consistent 1278:1287 Consistent 1278:1287 Consistent 1278:1287 Consistent with these changes we saw a decrease in the size of the hypertrophic zone with lower levels of Collagen-X. 35167946 1 64 mod modified 253:260 arg3 fucose 276:281 O-linked fucose 267:281 O-linked fucose 267:281 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 1 64 mod modified 253:260 arg1 TSRs 237:240 TSRs 237:240 TSRs 237:240 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 1 64 mod modified 253:260 arg1 repeats 228:234 Thrombospondin type 1 repeats 206:234 Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose 206:281 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 6 65 theme signaling 1267:1275 arg1 accumulation 1178:1189 an accumulation 1175:1189 an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling 1175:1275 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 35167946 6 66 theme fibrillin 1194:1202 arg1 accumulation 1178:1189 an accumulation 1175:1189 an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling 1175:1275 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 35167946 6 67 theme increased 1251:1259 arg1 signaling 1267:1275 increased TGF-β signaling 1251:1275 increased TGF-β signaling 1251:1275 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 35167946 1 68 theme extracellular 124:136 arg1 proteins 162:169 Many extracellular matrix (ECM) associated proteins 119:169 Many extracellular matrix (ECM) associated proteins that influence ECM properties 119:199 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 5 69 theme Pofut2 867:872 arg1 Loss 859:862 Loss 859:862 Loss of Pofut2 in the limb mesenchyme 859:895 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 0 70 theme ECM 65:67 arg1 remodeling 69:78 ECM remodeling 65:78 ECM remodeling 65:78 O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development. 35167946 11 71 contain has 1970:1972 arg1 modification 1877:1888 the O-fucose modification 1864:1888 the O-fucose modification on TSRs 1864:1896 In addition, these observations raise the possibility that the O-fucose modification on TSRs extends beyond promoting efficient trafficking of POFUT2 substrates and has the potential to influence their function in the extracellular environment. 35167946 11 71 contain has 1970:1972 arg2 potential 1978:1986 the potential to influence their function in the extracellular environment 1974:2047 the potential to influence their function in the extracellular environment 1974:2047 In addition, these observations raise the possibility that the O-fucose modification on TSRs extends beyond promoting efficient trafficking of POFUT2 substrates and has the potential to influence their function in the extracellular environment. 35167946 5 72 from Loss 859:862 arg1 mesenchyme 886:895 the limb mesenchyme 877:895 the limb mesenchyme 877:895 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 5 73 theme limb 881:884 arg1 mesenchyme 886:895 the limb mesenchyme 877:895 the limb mesenchyme 877:895 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 8 74 theme knockout 1452:1459 arg1 Pofut2 1445:1450 the Pofut2 knockout 1441:1459 the Pofut2 knockout 1441:1459 Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. 35167946 4 75 theme knockout 683:690 arg1 Pofut2 676:681 the Pofut2 knockout 672:690 the Pofut2 knockout 672:690 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 8 76 from effects 1430:1436 arg1 secretion 1464:1472 secretion 1464:1472 secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone 1464:1539 Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. 35167946 5 77 theme bones 946:950 arg1 shortening 916:925 significant shortening 904:925 significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins 904:1086 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 9 78 theme HEK293T 1688:1694 arg1 cells 1696:1700 POFUT2-null HEK293T cells 1676:1700 POFUT2-null HEK293T cells 1676:1700 In contrast, CCN2 and two other POFUT2 substrates important for bone development, ADAMTS6 and 10, showed a decrease in secretion from POFUT2-null HEK293T cells in vitro. 35167946 4 79 theme matrix 751:756 arg1 properties 758:767 extracellular matrix properties 737:767 extracellular matrix properties in vivo 737:775 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 5 80 with mice 1038:1041 arg1 mutations 1048:1056 mutations 1048:1056 mutations in ADAMTS or ADAMTSL proteins 1048:1086 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 5 81 from mutations 1048:1056 arg1 proteins 1079:1086 ADAMTS or ADAMTSL proteins 1061:1086 proteins 1079:1086 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 5 82 theme tendons 956:962 arg1 shortening 916:925 significant shortening 904:925 significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins 904:1086 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 4 83 theme in 769:770 arg1 properties 758:767 extracellular matrix properties 737:767 extracellular matrix properties in vivo 737:775 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 2 84 theme Protein 364:370 arg1 POFUT2 396:401 POFUT2 396:401 POFUT2 396:401 The O-fucose is added in the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) and is proposed to promote efficient trafficking of substrates. 35167946 2 84 theme Protein 364:370 arg1 O-fucosyltransferase-2 372:393 the enzyme Protein O-fucosyltransferase-2 353:393 the enzyme Protein O-fucosyltransferase-2 (POFUT2) 353:402 The O-fucose is added in the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) and is proposed to promote efficient trafficking of substrates. 35167946 8 85 theme substrates 1488:1497 arg1 secretion 1464:1472 secretion 1464:1472 secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone 1464:1539 Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. 35167946 4 86 theme substrates 719:728 arg1 secretion 699:707 the secretion 695:707 the secretion of POFUT2 substrates 695:728 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 6 87 from day 1130:1132 arg1 evident 1109:1115 evident 1109:1115 evident 1109:1115 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 35167946 0 88 theme type 33:36 arg1 repeats 40:46 thrombospondin type 1 repeats 18:46 thrombospondin type 1 repeats 18:46 O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development. 35167946 1 89 theme O-linked 267:274 arg1 fucose 276:281 O-linked fucose 267:281 O-linked fucose 267:281 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 10 90 theme combined 1718:1725 arg1 results 1727:1733 These combined results 1712:1733 These combined results 1712:1733 These combined results suggest that the impact of the Pofut2 mutation is cell-type specific. 35167946 10 91 theme Pofut2 1766:1771 arg1 mutation 1773:1780 the Pofut2 mutation 1762:1780 the Pofut2 mutation 1762:1780 These combined results suggest that the impact of the Pofut2 mutation is cell-type specific. 35167946 0 92 theme repeats 40:46 arg1 O-fucosylation 0:13 O-fucosylation 0:13 O-fucosylation of thrombospondin type 1 repeats 0:46 O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development. 35167946 1 93 theme Thrombospondin 206:219 arg1 TSRs 237:240 TSRs 237:240 TSRs 237:240 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 1 93 theme Thrombospondin 206:219 arg1 repeats 228:234 Thrombospondin type 1 repeats 206:234 Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose 206:281 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 5 94 theme musculoskeletal 995:1009 arg1 dysplasias 1011:1020 the musculoskeletal dysplasias 991:1020 the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins 991:1086 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 7 95 with size 1333:1336 arg1 levels 1374:1379 lower levels 1368:1379 lower levels of Collagen-X 1368:1393 Consistent with these changes we saw a decrease in the size of the hypertrophic zone with lower levels of Collagen-X. 35167946 8 96 from secretion 1464:1472 arg1 bone 1536:1539 the developing bone 1521:1539 the developing bone 1521:1539 Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. 35167946 2 97 theme efficient 431:439 arg1 trafficking 441:451 efficient trafficking 431:451 efficient trafficking of substrates 431:465 The O-fucose is added in the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) and is proposed to promote efficient trafficking of substrates. 35167946 4 98 theme developing 803:812 arg1 mesenchyme 819:828 the developing limb mesenchyme 799:828 the developing limb mesenchyme 799:828 To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2 substrates and on extracellular matrix properties in vivo, we deleted Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase. 35167946 2 99 theme endoplasmic 313:323 arg1 reticulum 325:333 the endoplasmic reticulum 309:333 the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) 309:402 The O-fucose is added in the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) and is proposed to promote efficient trafficking of substrates. 35167946 5 100 theme stiff 968:972 arg1 joint 974:978 stiff joint 968:978 stiff joint 968:978 Loss of Pofut2 in the limb mesenchyme caused significant shortening of the limbs, long bones and tendons and stiff joint resembling the musculoskeletal dysplasias in human and in mice with mutations in ADAMTS or ADAMTSL proteins. 35167946 11 101 theme O-fucose 1868:1875 arg1 modification 1877:1888 the O-fucose modification 1864:1888 the O-fucose modification on TSRs 1864:1896 In addition, these observations raise the possibility that the O-fucose modification on TSRs extends beyond promoting efficient trafficking of POFUT2 substrates and has the potential to influence their function in the extracellular environment. 35167946 8 102 theme developing 1525:1534 arg1 bone 1536:1539 the developing bone 1521:1539 the developing bone 1521:1539 Unexpectedly, we observed minimal effects of the Pofut2 knockout on secretion of two POFUT2 substrates, CCN2 or ADAMTS17, in the developing bone. 35167946 1 103 contain have 201:204 arg1 proteins 162:169 Many extracellular matrix (ECM) associated proteins 119:169 Many extracellular matrix (ECM) associated proteins that influence ECM properties 119:199 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 1 103 contain have 201:204 arg2 TSRs 237:240 TSRs 237:240 TSRs 237:240 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 1 103 contain have 201:204 arg2 repeats 228:234 Thrombospondin type 1 repeats 206:234 Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose 206:281 Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. 35167946 6 104 theme Limb 1089:1092 arg1 shortening 1094:1103 Limb shortening 1089:1103 Limb shortening 1089:1103 Limb shortening was evident at embryonic day 14.5 where loss of O-fucosylation led to an accumulation of fibrillin 2 (FBN2), decreased BMP and IHH signaling, and increased TGF-β signaling. 37367731 5 0 theme pathways 1212:1219 arg1 activation 1188:1197 the activation 1184:1197 the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis 1184:1334 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 0 theme pathways 1212:1219 arg1 acquisition 1124:1134 the acquisition 1120:1134 the acquisition of the multidrug resistance (MDR) phenotype 1120:1178 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 1 1 theme metabolic 169:177 arg1 reprogramming 179:191 metabolic reprogramming 169:191 metabolic reprogramming 169:191 Cancer cells are characterized by metabolic reprogramming, which enables their survival in of-ten inhospitable conditions. 37367731 5 2 link O-linked 1031:1038 arg1 glycans 1040:1046 unusual/truncated O-linked glycans 1013:1046 unusual/truncated O-linked glycans 1013:1046 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 2 3 theme transformed 373:383 arg1 cells 385:389 transformed cells 373:389 transformed cells 373:389 A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. 37367731 3 4 from feature 447:453 arg1 association 459:469 association 459:469 association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates 459:562 Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. 37367731 2 5 theme re-cent 319:325 arg1 years 327:331 re-cent years 319:331 re-cent years 319:331 A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. 37367731 0 6 theme Multidrug 103:111 arg1 Resistance 113:122 Multidrug Resistance 103:122 Multidrug Resistance 103:122 Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer. 37367731 4 7 theme essential 844:852 arg1 events 837:842 multifactorial events 822:842 multifactorial events essential for the development and/or progres-sion of the disease 822:907 The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. 37367731 2 8 theme cells 385:389 arg1 hallmark 361:368 a hallmark 359:368 a hallmark of transformed cells 359:389 A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. 37367731 5 9 theme glycobiology 952:963 arg1 importance 938:947 the importance 934:947 the importance of glycobiology in modern medi-cine 934:983 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 2 10 theme metabolism 428:437 arg1 example 281:287 A very well-documented example 258:287 A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells 258:389 A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. 37367731 2 10 theme metabolism 428:437 arg1 reprogramming 398:410 the reprogramming 394:410 the reprogramming of carbohydrate metabolism 394:437 A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. 37367731 2 11 theme carbohydrate 415:426 arg1 metabolism 428:437 carbohydrate metabolism 415:437 carbohydrate metabolism 415:437 A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. 37367731 5 12 theme unusual/truncated 1013:1029 arg1 glycans 1040:1046 unusual/truncated O-linked glycans 1013:1046 unusual/truncated O-linked glycans 1013:1046 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 4 13 theme latest 730:735 arg1 studies 737:743 The latest studies 726:743 The latest studies 726:743 The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. 37367731 0 14 theme Bittersweet 0:10 arg1 Sugars 12:17 Bittersweet Sugars 0:17 Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer. 0:133 Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer. 37367731 5 15 theme EMT 1276:1278 arg1 process 1281:1287 the epithelial-mesenchymal transition (EMT) process 1237:1287 the epithelial-mesenchymal transition (EMT) process 1237:1287 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 15 theme EMT 1276:1278 arg1 event 1293:1297 an event 1290:1297 an event deeply linked with cancer metastasis 1290:1334 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 16 theme resistance 1153:1162 arg1 phenotype 1170:1178 the multidrug resistance (MDR) phenotype 1139:1178 the multidrug resistance (MDR) phenotype 1139:1178 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 17 theme O-linked 1031:1038 arg1 glycans 1040:1046 unusual/truncated O-linked glycans 1013:1046 unusual/truncated O-linked glycans 1013:1046 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 18 theme MDR 1165:1167 arg1 phenotype 1170:1178 the multidrug resistance (MDR) phenotype 1139:1178 the multidrug resistance (MDR) phenotype 1139:1178 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 0 19 dep Sugars 12:17 arg1 Connect 54:60 Connect 54:60 May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer 50:132 Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer. 37367731 5 20 theme glycans 1040:1046 arg1 ability 1002:1008 the ability 998:1008 the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression 998:1117 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 4 21 theme multifactorial 822:835 arg1 events 837:842 multifactorial events 822:842 multifactorial events essential for the development and/or progres-sion of the disease 822:907 The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. 37367731 4 22 dep development 862:872 arg1 the 858:860 the 858:860 the 858:860 The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. 37367731 0 23 theme Glycan 32:37 arg1 Structures 39:48 Unusual Glycan Structures 24:48 Unusual Glycan Structures 24:48 Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer. 37367731 4 24 theme glycophenotypic 768:782 arg1 alterations 784:794 glycophenotypic alterations 768:794 glycophenotypic alterations 768:794 The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. 37367731 3 25 theme healthy 709:715 arg1 tissues 717:723 healthy tissues 709:723 healthy tissues 709:723 Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. 37367731 1 26 theme of-ten 226:231 arg1 conditions 246:255 of-ten inhospitable conditions 226:255 of-ten inhospitable conditions 226:255 Cancer cells are characterized by metabolic reprogramming, which enables their survival in of-ten inhospitable conditions. 37367731 0 27 theme Unusual 24:30 arg1 Structures 39:48 Unusual Glycan Structures 24:48 Unusual Glycan Structures 24:48 Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer. 37367731 3 28 theme atypical 655:662 arg1 glycans 664:670 structurally atypical glycans 642:670 structurally atypical glycans 642:670 Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. 37367731 1 29 theme inhospitable 233:244 arg1 conditions 246:255 of-ten inhospitable conditions 226:255 of-ten inhospitable conditions 226:255 Cancer cells are characterized by metabolic reprogramming, which enables their survival in of-ten inhospitable conditions. 37367731 5 30 theme modern 968:973 arg1 medi-cine 975:983 modern medi-cine 968:983 modern medi-cine 968:983 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 31 theme phenotype 1170:1178 arg1 activation 1188:1197 the activation 1184:1197 the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis 1184:1334 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 31 theme phenotype 1170:1178 arg1 acquisition 1124:1134 the acquisition 1120:1134 the acquisition of the multidrug resistance (MDR) phenotype 1120:1178 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 32 theme transition 1264:1273 arg1 process 1281:1287 the epithelial-mesenchymal transition (EMT) process 1237:1287 the epithelial-mesenchymal transition (EMT) process 1237:1287 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 32 theme transition 1264:1273 arg1 event 1293:1297 an event 1290:1297 an event deeply linked with cancer metastasis 1290:1334 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 1 33 from survival 214:221 arg1 conditions 246:255 of-ten inhospitable conditions 226:255 of-ten inhospitable conditions 226:255 Cancer cells are characterized by metabolic reprogramming, which enables their survival in of-ten inhospitable conditions. 37367731 1 34 theme Cancer 135:140 arg1 cells 142:146 Cancer cells 135:146 Cancer cells 135:146 Cancer cells are characterized by metabolic reprogramming, which enables their survival in of-ten inhospitable conditions. 37367731 5 35 theme cancer 1100:1105 arg1 progression 1107:1117 cancer progression 1100:1117 cancer progression 1100:1117 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 3 36 with association 459:469 arg1 expression 493:502 the differential expression 476:502 the differential expression of en-zymes involved in the biosynthesis of glycoconjugates 476:562 Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. 37367731 5 37 dep address 926:932 arg1 activation 1188:1197 the activation 1184:1197 the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis 1184:1334 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 37 dep address 926:932 arg1 acquisition 1124:1134 the acquisition 1120:1134 the acquisition of the multidrug resistance (MDR) phenotype 1120:1178 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 38 theme essential 1076:1084 arg1 phenomena 1086:1094 essential phenomena 1076:1094 essential phenomena 1076:1094 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 4 39 theme disease 901:907 arg1 development 862:872 development 862:872 development 862:872 The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. 37367731 3 40 theme en-zymes 507:514 arg1 expression 493:502 the differential expression 476:502 the differential expression of en-zymes involved in the biosynthesis of glycoconjugates 476:562 Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. 37367731 5 41 theme multidrug 1143:1151 arg1 phenotype 1170:1178 the multidrug resistance (MDR) phenotype 1139:1178 the multidrug resistance (MDR) phenotype 1139:1178 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 42 theme cancer 1318:1323 arg1 metastasis 1325:1334 cancer metastasis 1318:1334 cancer metastasis 1318:1334 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 0 43 theme Epithelial-to-Mesenchymal 62:86 arg1 Transition 88:97 Epithelial-to-Mesenchymal Transition 62:97 Epithelial-to-Mesenchymal Transition 62:97 Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer. 37367731 3 44 theme differential 480:491 arg1 expression 493:502 the differential expression 476:502 the differential expression of en-zymes involved in the biosynthesis of glycoconjugates 476:562 Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. 37367731 3 45 theme glycans 664:670 arg1 expression 628:637 the expression 624:637 the expression of structurally atypical glycans 624:670 Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. 37367731 3 46 theme glycoconjugates 548:562 arg1 biosynthesis 532:543 the biosynthesis 528:543 the biosynthesis of glycoconjugates 528:562 Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. 37367731 5 47 theme molecular 1202:1210 arg1 pathways 1212:1219 molecular pathways 1202:1219 molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis 1202:1334 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 2 48 theme well-documented 265:279 arg1 example 281:287 A very well-documented example 258:287 A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells 258:389 A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. 37367731 2 48 theme well-documented 265:279 arg1 reprogramming 398:410 the reprogramming 394:410 the reprogramming of carbohydrate metabolism 394:437 A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. 37367731 5 49 from importance 938:947 arg1 medi-cine 975:983 modern medi-cine 968:983 modern medi-cine 968:983 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 50 theme epithelial-mesenchymal 1241:1262 arg1 process 1281:1287 the epithelial-mesenchymal transition (EMT) process 1237:1287 the epithelial-mesenchymal transition (EMT) process 1237:1287 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37367731 5 50 theme epithelial-mesenchymal 1241:1262 arg1 event 1293:1297 an event 1290:1297 an event deeply linked with cancer metastasis 1290:1334 Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis. 37054524 0 0 theme molecular 82:90 arg1 dynamics 92:99 molecular dynamics 82:99 molecular dynamics 82:99 In silico drug repurposing by combining machine learning classification model and molecular dynamics to identify a potential OGT inhibitor. 37054524 5 1 theme classification 860:873 arg1 model 875:879 a classification model 858:879 a classification model using docking scores and ligand descriptors 858:923 We developed a classification model using docking scores and ligand descriptors. 37054524 2 2 from anomalies 421:429 arg1 process 439:445 this process 434:445 this process 434:445 The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. 37054524 8 3 theme molecular 1300:1308 arg1 dynamics 1310:1317 The molecular dynamics 1296:1317 The molecular dynamics simulation 1296:1328 The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. 37054524 1 4 theme serine 264:269 arg1 group 255:259 the hydroxyl group 242:259 the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 242:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 4 theme serine 264:269 arg1 threonine 274:282 threonine 274:282 threonine 274:282 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 4 theme serine 264:269 arg1 serine 264:269 serine 264:269 serine 264:269 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 2 5 theme diseases 478:485 arg1 development 463:473 the development 459:473 the development of diseases associated with metabolic imbalance, such as diabetes and cancer 459:550 The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. 37054524 5 6 theme docking 887:893 arg1 scores 895:900 docking scores 887:900 docking scores 887:900 We developed a classification model using docking scores and ligand descriptors. 37054524 6 7 theme statistical 988:998 arg1 values 1000:1005 excellent statistical values 978:1005 excellent statistical values 978:1005 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 8 8 theme H-bond 1349:1354 arg1 interactions 1356:1367 H-bond interactions 1349:1367 H-bond interactions with the C- and N-catalytic domains 1349:1403 The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. 37054524 6 9 theme correlation 1148:1158 arg1 coefficient 1160:1170 Matthew's correlation coefficient 1138:1170 Matthew's correlation coefficient greater than 0.8 1138:1187 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 7 10 with interaction 1257:1267 arg1 domain 1288:1293 the OGT C-Cat domain 1274:1293 the OGT C-Cat domain 1274:1293 The pose analysis obtained by molecular docking showed only H-bond interaction with the OGT C-Cat domain. 37054524 1 11 theme threonine 274:282 arg1 group 255:259 the hydroxyl group 242:259 the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 242:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 11 theme threonine 274:282 arg1 threonine 274:282 threonine 274:282 threonine 274:282 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 11 theme threonine 274:282 arg1 serine 264:269 serine 264:269 serine 264:269 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 4 12 from dataset 836:842 arg1 models 810:815 consensus machine learning (ML) models 778:815 consensus machine learning (ML) models from an imbalanced dataset 778:842 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 8 13 theme dynamics 1310:1317 arg1 simulation 1319:1328 The molecular dynamics simulation 1296:1328 The molecular dynamics simulation 1296:1328 The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. 37054524 7 14 theme H-bond 1250:1255 arg1 interaction 1257:1267 only H-bond interaction 1245:1267 only H-bond interaction with the OGT C-Cat domain 1245:1293 The pose analysis obtained by molecular docking showed only H-bond interaction with the OGT C-Cat domain. 37054524 6 15 theme algorithms 1031:1040 arg1 algorithms 1031:1040 the seven ML algorithms 1018:1040 the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy 1018:1123 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 6 15 theme algorithms 1031:1040 arg1 five 1010:1013 five 1010:1013 five 1010:1013 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 4 16 theme drugs 764:768 arg1 screening 738:746 virtual screening 730:746 virtual screening of FDA-approved drugs 730:768 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 5 17 theme ligand 906:911 arg1 descriptors 913:923 ligand descriptors 906:923 ligand descriptors 906:923 We developed a classification model using docking scores and ligand descriptors. 37054524 9 18 theme OGT 1541:1543 arg1 celecoxib 1508:1516 the non-steroidal anti-inflammatory celecoxib 1472:1516 the non-steroidal anti-inflammatory celecoxib 1472:1516 Our results showed that the non-steroidal anti-inflammatory celecoxib could be a potentially OGT inhibitor. 37054524 9 18 theme OGT 1541:1543 arg1 inhibitor 1545:1553 a potentially OGT inhibitor 1527:1553 a potentially OGT inhibitor 1527:1553 Our results showed that the non-steroidal anti-inflammatory celecoxib could be a potentially OGT inhibitor. 37054524 8 19 with interactions 1356:1367 arg1 domains 1397:1403 the C- and N-catalytic domains 1374:1403 domains 1397:1403 The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. 37054524 7 20 theme C-Cat 1282:1286 arg1 domain 1288:1293 the OGT C-Cat domain 1274:1293 the OGT C-Cat domain 1274:1293 The pose analysis obtained by molecular docking showed only H-bond interaction with the OGT C-Cat domain. 37054524 4 21 theme FDA-approved 751:762 arg1 drugs 764:768 FDA-approved drugs 751:768 FDA-approved drugs 751:768 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 6 22 theme training 1068:1075 arg1 set 1077:1079 the training set 1064:1079 the training set 1064:1079 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 7 23 theme pose 1194:1197 arg1 analysis 1199:1206 The pose analysis 1190:1206 The pose analysis obtained by molecular docking 1190:1236 The pose analysis obtained by molecular docking showed only H-bond interaction with the OGT C-Cat domain. 37054524 0 24 theme In 0:1 arg1 drug 10:13 In silico drug 0:13 In silico drug 0:13 In silico drug repurposing by combining machine learning classification model and molecular dynamics to identify a potential OGT inhibitor. 37054524 6 25 theme greater 1172:1178 arg1 coefficient 1160:1170 Matthew's correlation coefficient 1138:1170 Matthew's correlation coefficient greater than 0.8 1138:1187 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 1 26 gly glycosylation 225:237 arg2 serine 264:269 serine 264:269 serine 264:269 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 26 gly glycosylation 225:237 arg1 group 255:259 the hydroxyl group 242:259 the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 242:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 26 gly glycosylation 225:237 arg2 threonine 274:282 threonine 274:282 threonine 274:282 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 26 gly glycosylation 225:237 arg1 serine 264:269 serine 264:269 serine 264:269 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 26 gly glycosylation 225:237 arg1 threonine 274:282 threonine 274:282 threonine 274:282 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 26 gly glycosylation 225:237 arg2 group 255:259 the hydroxyl group 242:259 the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 242:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 9 27 theme non-steroidal 1476:1488 arg1 celecoxib 1508:1516 the non-steroidal anti-inflammatory celecoxib 1472:1516 the non-steroidal anti-inflammatory celecoxib 1472:1516 Our results showed that the non-steroidal anti-inflammatory celecoxib could be a potentially OGT inhibitor. 37054524 9 27 theme non-steroidal 1476:1488 arg1 inhibitor 1545:1553 a potentially OGT inhibitor 1527:1553 a potentially OGT inhibitor 1527:1553 Our results showed that the non-steroidal anti-inflammatory celecoxib could be a potentially OGT inhibitor. 37054524 1 28 theme unique 185:190 arg1 N-acetylglucosamine 149:167 O-linked N-acetylglucosamine 140:167 O-linked N-acetylglucosamine (O-GlcNAc) 140:178 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 28 theme unique 185:190 arg1 glycosylation 225:237 a unique intracellular post-translational glycosylation 183:237 a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 183:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 29 theme nuclear 296:302 arg1 proteins 335:342 nuclear, cytoplasmic and mitochondrial proteins 296:342 nuclear, cytoplasmic and mitochondrial proteins 296:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 0 30 theme OGT 125:127 arg1 inhibitor 129:137 a potential OGT inhibitor 113:137 a potential OGT inhibitor 113:137 In silico drug repurposing by combining machine learning classification model and molecular dynamics to identify a potential OGT inhibitor. 37054524 3 31 theme Repurposing 553:563 arg1 tool 601:604 an attractive tool 587:604 an attractive tool to discover new targets reducing time and costs in the drug design 587:671 Repurposing approved drugs can be an attractive tool to discover new targets reducing time and costs in the drug design. 37054524 3 31 theme Repurposing 553:563 arg1 drugs 574:578 Repurposing approved drugs 553:578 Repurposing approved drugs 553:578 Repurposing approved drugs can be an attractive tool to discover new targets reducing time and costs in the drug design. 37054524 1 32 theme intracellular 192:204 arg1 N-acetylglucosamine 149:167 O-linked N-acetylglucosamine 140:167 O-linked N-acetylglucosamine (O-GlcNAc) 140:178 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 32 theme intracellular 192:204 arg1 glycosylation 225:237 a unique intracellular post-translational glycosylation 183:237 a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 183:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 0 33 theme potential 115:123 arg1 inhibitor 129:137 a potential OGT inhibitor 113:137 a potential OGT inhibitor 113:137 In silico drug repurposing by combining machine learning classification model and molecular dynamics to identify a potential OGT inhibitor. 37054524 3 34 theme approved 565:572 arg1 tool 601:604 an attractive tool 587:604 an attractive tool to discover new targets reducing time and costs in the drug design 587:671 Repurposing approved drugs can be an attractive tool to discover new targets reducing time and costs in the drug design. 37054524 3 34 theme approved 565:572 arg1 drugs 574:578 Repurposing approved drugs 553:578 Repurposing approved drugs 553:578 Repurposing approved drugs can be an attractive tool to discover new targets reducing time and costs in the drug design. 37054524 1 35 theme post-translational 206:223 arg1 N-acetylglucosamine 149:167 O-linked N-acetylglucosamine 140:167 O-linked N-acetylglucosamine (O-GlcNAc) 140:178 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 35 theme post-translational 206:223 arg1 glycosylation 225:237 a unique intracellular post-translational glycosylation 183:237 a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 183:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 36 theme cytoplasmic 305:315 arg1 proteins 335:342 nuclear, cytoplasmic and mitochondrial proteins 296:342 nuclear, cytoplasmic and mitochondrial proteins 296:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 37 link O-linked 140:147 arg1 N-acetylglucosamine 149:167 O-linked N-acetylglucosamine 140:167 O-linked N-acetylglucosamine (O-GlcNAc) 140:178 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 37 link O-linked 140:147 arg1 glycosylation 225:237 a unique intracellular post-translational glycosylation 183:237 a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 183:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 37 link O-linked 140:147 arg1 O-GlcNAc 170:177 O-GlcNAc 170:177 O-GlcNAc 170:177 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 7 38 theme molecular 1220:1228 arg1 docking 1230:1236 molecular docking 1220:1236 molecular docking 1220:1236 The pose analysis obtained by molecular docking showed only H-bond interaction with the OGT C-Cat domain. 37054524 3 39 theme attractive 590:599 arg1 tool 601:604 an attractive tool 587:604 an attractive tool to discover new targets reducing time and costs in the drug design 587:671 Repurposing approved drugs can be an attractive tool to discover new targets reducing time and costs in the drug design. 37054524 3 39 theme attractive 590:599 arg1 drugs 574:578 Repurposing approved drugs 553:578 Repurposing approved drugs 553:578 Repurposing approved drugs can be an attractive tool to discover new targets reducing time and costs in the drug design. 37054524 6 40 theme ML 1028:1029 arg1 algorithms 1031:1040 the seven ML algorithms 1018:1040 the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy 1018:1123 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 8 41 dep showed 1330:1335 arg1 allowed 1405:1411 allowed 1405:1411 showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site 1330:1445 The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. 37054524 6 42 dep approach 936:943 arg1 resampling 948:957 resampling 948:957 to resampling the dataset 945:969 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 0 43 theme learning 48:55 arg1 model 72:76 machine learning classification model 40:76 machine learning classification model 40:76 In silico drug repurposing by combining machine learning classification model and molecular dynamics to identify a potential OGT inhibitor. 37054524 1 44 theme mitochondrial 321:333 arg1 proteins 335:342 nuclear, cytoplasmic and mitochondrial proteins 296:342 nuclear, cytoplasmic and mitochondrial proteins 296:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 45 from group 255:259 arg1 proteins 335:342 nuclear, cytoplasmic and mitochondrial proteins 296:342 nuclear, cytoplasmic and mitochondrial proteins 296:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 45 from group 255:259 arg1 glycosylation 225:237 a unique intracellular post-translational glycosylation 183:237 a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 183:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 45 from group 255:259 arg1 N-acetylglucosamine 149:167 O-linked N-acetylglucosamine 140:167 O-linked N-acetylglucosamine (O-GlcNAc) 140:178 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 4 46 theme imbalanced 825:834 arg1 dataset 836:842 an imbalanced dataset 822:842 an imbalanced dataset 822:842 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 4 47 theme drug 695:698 arg1 targets 719:725 drug repurposing to OGT targets 695:725 drug repurposing to OGT targets 695:725 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 0 48 theme machine 40:46 arg1 learning 48:55 machine learning 40:55 machine learning classification model 40:76 In silico drug repurposing by combining machine learning classification model and molecular dynamics to identify a potential OGT inhibitor. 37054524 3 49 theme drug 661:664 arg1 design 666:671 the drug design 657:671 the drug design 657:671 Repurposing approved drugs can be an attractive tool to discover new targets reducing time and costs in the drug design. 37054524 8 50 theme C- 1378:1379 arg1 domains 1397:1403 the C- and N-catalytic domains 1374:1403 domains 1397:1403 The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. 37054524 2 51 theme O-GlcNAc 356:363 arg1 OGT 378:380 OGT 378:380 OGT 378:380 The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. 37054524 2 51 theme O-GlcNAc 356:363 arg1 responsible 386:396 responsible 386:396 responsible 386:396 The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. 37054524 2 51 theme O-GlcNAc 356:363 arg1 transferase 365:375 The enzyme O-GlcNAc transferase 345:375 The enzyme O-GlcNAc transferase (OGT) 345:381 The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. 37054524 4 52 theme machine 788:794 arg1 ML 806:807 ML 806:807 ML 806:807 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 4 52 theme machine 788:794 arg1 learning 796:803 consensus machine learning 778:803 consensus machine learning (ML) models from an imbalanced dataset 778:842 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 8 53 theme binding 1434:1440 arg1 site 1442:1445 the binding site 1430:1445 the binding site 1430:1445 The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. 37054524 4 54 theme consensus 778:786 arg1 ML 806:807 ML 806:807 ML 806:807 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 4 54 theme consensus 778:786 arg1 learning 796:803 consensus machine learning 778:803 consensus machine learning (ML) models from an imbalanced dataset 778:842 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 3 55 theme new 618:620 arg1 targets 622:628 new targets 618:628 new targets 618:628 Repurposing approved drugs can be an attractive tool to discover new targets reducing time and costs in the drug design. 37054524 2 56 theme enzyme 349:354 arg1 OGT 378:380 OGT 378:380 OGT 378:380 The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. 37054524 2 56 theme enzyme 349:354 arg1 responsible 386:396 responsible 386:396 responsible 386:396 The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. 37054524 2 56 theme enzyme 349:354 arg1 transferase 365:375 The enzyme O-GlcNAc transferase 345:375 The enzyme O-GlcNAc transferase (OGT) 345:381 The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. 37054524 4 57 theme virtual 730:736 arg1 screening 738:746 virtual screening 730:746 virtual screening of FDA-approved drugs 730:768 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 6 58 theme excellent 978:986 arg1 values 1000:1005 excellent statistical values 978:1005 excellent statistical values 978:1005 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 6 59 dep algorithms 1031:1040 arg1 create 1045:1050 create 1045:1050 create 1045:1050 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 1 60 dep serine 264:269 arg1 residues 284:291 residues 284:291 residues 284:291 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 8 61 theme N-catalytic 1385:1395 arg1 domains 1397:1403 the C- and N-catalytic domains 1374:1403 domains 1397:1403 The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. 37054524 6 62 from set 1077:1079 arg1 models 1052:1057 models 1052:1057 models from the training set 1052:1079 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 37054524 4 63 theme repurposing 700:710 arg1 targets 719:725 drug repurposing to OGT targets 695:725 drug repurposing to OGT targets 695:725 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 1 64 theme hydroxyl 246:253 arg1 group 255:259 the hydroxyl group 242:259 the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 242:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 64 theme hydroxyl 246:253 arg1 threonine 274:282 threonine 274:282 threonine 274:282 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 64 theme hydroxyl 246:253 arg1 serine 264:269 serine 264:269 serine 264:269 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 2 65 theme metabolic 503:511 arg1 imbalance 513:521 metabolic imbalance 503:521 metabolic imbalance 503:521 The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. 37054524 8 66 theme interactions 1356:1367 arg1 lack 1341:1344 the lack 1337:1344 the lack of H-bond interactions with the C- and N-catalytic domains 1337:1403 The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. 37054524 4 67 theme learning 796:803 arg1 models 810:815 consensus machine learning (ML) models 778:815 consensus machine learning (ML) models from an imbalanced dataset 778:842 This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. 37054524 7 68 theme OGT 1278:1280 arg1 domain 1288:1293 the OGT C-Cat domain 1274:1293 the OGT C-Cat domain 1274:1293 The pose analysis obtained by molecular docking showed only H-bond interaction with the OGT C-Cat domain. 37054524 1 69 theme O-linked 140:147 arg1 N-acetylglucosamine 149:167 O-linked N-acetylglucosamine 140:167 O-linked N-acetylglucosamine (O-GlcNAc) 140:178 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 69 theme O-linked 140:147 arg1 glycosylation 225:237 a unique intracellular post-translational glycosylation 183:237 a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins 183:342 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 1 69 theme O-linked 140:147 arg1 O-GlcNAc 170:177 O-GlcNAc 170:177 O-GlcNAc 170:177 O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. 37054524 0 70 theme classification 57:70 arg1 model 72:76 machine learning classification model 40:76 machine learning classification model 40:76 In silico drug repurposing by combining machine learning classification model and molecular dynamics to identify a potential OGT inhibitor. 37054524 0 71 dep In 0:1 arg1 silico 3:8 silico 3:8 silico 3:8 In silico drug repurposing by combining machine learning classification model and molecular dynamics to identify a potential OGT inhibitor. 37054524 9 72 theme anti-inflammatory 1490:1506 arg1 celecoxib 1508:1516 the non-steroidal anti-inflammatory celecoxib 1472:1516 the non-steroidal anti-inflammatory celecoxib 1472:1516 Our results showed that the non-steroidal anti-inflammatory celecoxib could be a potentially OGT inhibitor. 37054524 9 72 theme anti-inflammatory 1490:1506 arg1 inhibitor 1545:1553 a potentially OGT inhibitor 1527:1553 a potentially OGT inhibitor 1527:1553 Our results showed that the non-steroidal anti-inflammatory celecoxib could be a potentially OGT inhibitor. 37054524 6 73 theme SMOTE 930:934 arg1 approach 936:943 The SMOTE approach 926:943 The SMOTE approach to resampling the dataset 926:969 The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. 36740243 9 0 theme many 1406:1409 arg1 functions 1419:1427 many protein functions 1406:1427 many protein functions 1406:1427 A comparison with the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome revealed that 30% of AtSPY targets were also O-GlcNAcylated, indicating that these distinct glycosylations could co-regulate many protein functions. 36740243 5 1 theme few 696:698 arg1 targets 706:712 very few AtSPY targets 691:712 very few AtSPY targets 691:712 However, very few AtSPY targets are known. 36740243 7 2 theme RNA 1047:1049 arg1 splicing 1051:1058 RNA splicing 1047:1058 RNA splicing 1047:1058 Most AtSPY targets were nuclear proteins that function in DNA repair, transcription, RNA splicing, and nucleocytoplasmic transport. 36740243 1 3 theme protein 148:154 arg1 SPINDLY 105:111 SPINDLY 105:111 SPINDLY (SPY) 105:117 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 1 3 theme protein 148:154 arg1 O-fucosyltransferase 156:175 a novel nucleocytoplasmic protein O-fucosyltransferase 122:175 a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues 122:275 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 7 4 theme Most 962:965 arg1 targets 973:979 Most AtSPY targets 962:979 Most AtSPY targets 962:979 Most AtSPY targets were nuclear proteins that function in DNA repair, transcription, RNA splicing, and nucleocytoplasmic transport. 36740243 1 5 theme residues 268:275 arg1 O-fucosylation 233:246 O-fucosylation 233:246 O-fucosylation of specific Ser/Thr residues 233:275 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 4 6 theme mutants 571:577 arg1 phenotypes 553:562 The pleiotropic phenotypes 537:562 The pleiotropic phenotypes of spy mutants 537:577 The pleiotropic phenotypes of spy mutants point to the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways. 36740243 5 7 theme AtSPY 700:704 arg1 targets 706:712 very few AtSPY targets 691:712 very few AtSPY targets 691:712 However, very few AtSPY targets are known. 36740243 6 8 theme peptides 864:871 arg1 purification 834:845 the purification 830:845 the purification of O-fucosylated peptides 830:871 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 8 9 theme Cytoplasmic 1094:1104 arg1 targets 1112:1118 Cytoplasmic AtSPY targets 1094:1118 Cytoplasmic AtSPY targets 1094:1118 Cytoplasmic AtSPY targets were involved in microtubule-mediated cell division/growth and protein folding. 36740243 8 10 theme AtSPY 1106:1110 arg1 targets 1112:1118 Cytoplasmic AtSPY targets 1094:1118 Cytoplasmic AtSPY targets 1094:1118 Cytoplasmic AtSPY targets were involved in microtubule-mediated cell division/growth and protein folding. 36740243 4 11 theme spy 567:569 arg1 mutants 571:577 spy mutants 567:577 spy mutants 567:577 The pleiotropic phenotypes of spy mutants point to the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways. 36740243 1 12 gly O-fucosylation 233:246 arg1 residues 268:275 specific Ser/Thr residues 251:275 specific Ser/Thr residues 251:275 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 6 13 theme electron 915:922 arg1 analysis 952:959 electron transfer dissociation-MS/MS analysis 915:959 electron transfer dissociation-MS/MS analysis 915:959 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 6 14 theme SPY 748:750 arg1 targets 752:758 88 SPY targets 745:758 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana 745:824 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 10 15 theme nuclear 1501:1507 arg1 proteins 1525:1532 many key nuclear and cytoplasmic proteins 1492:1532 many key nuclear and cytoplasmic proteins 1492:1532 This study unveiled the roles of O-fucosylation in modulating many key nuclear and cytoplasmic proteins and provided a valuable resource for elucidating the regulatory mechanisms involved. 36740243 3 16 theme plant 489:493 arg1 responses 495:503 plant responses 489:503 plant responses to biotic and abiotic stresses 489:534 AtSPY also regulates the circadian clock and plant responses to biotic and abiotic stresses. 36740243 4 17 theme pleiotropic 541:551 arg1 phenotypes 553:562 The pleiotropic phenotypes 537:562 The pleiotropic phenotypes of spy mutants 537:577 The pleiotropic phenotypes of spy mutants point to the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways. 36740243 4 18 theme key 627:629 arg1 proteins 631:638 key proteins 627:638 key proteins functioning in diverse cellular pathways 627:679 The pleiotropic phenotypes of spy mutants point to the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways. 36740243 9 19 theme AtSPY 1302:1306 arg1 targets 1308:1314 AtSPY targets 1302:1314 AtSPY targets 1302:1314 A comparison with the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome revealed that 30% of AtSPY targets were also O-GlcNAcylated, indicating that these distinct glycosylations could co-regulate many protein functions. 36740243 10 20 theme valuable 1549:1556 arg1 resource 1558:1565 a valuable resource 1547:1565 a valuable resource for elucidating the regulatory mechanisms involved 1547:1616 This study unveiled the roles of O-fucosylation in modulating many key nuclear and cytoplasmic proteins and provided a valuable resource for elucidating the regulatory mechanisms involved. 36740243 0 21 theme O-fucosylates 8:20 arg1 proteins 46:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins 0:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins 0:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins involved in diverse cellular processes in plants. 36740243 6 22 theme dissociation-MS/MS 933:950 arg1 analysis 952:959 electron transfer dissociation-MS/MS analysis 915:959 electron transfer dissociation-MS/MS analysis 915:959 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 8 23 theme cell 1158:1161 arg1 division/growth 1163:1177 microtubule-mediated cell division/growth 1137:1177 microtubule-mediated cell division/growth 1137:1177 Cytoplasmic AtSPY targets were involved in microtubule-mediated cell division/growth and protein folding. 36740243 9 24 theme targets 1308:1314 arg1 % 1297:1297 30% 1295:1297 30% of AtSPY targets 1295:1314 A comparison with the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome revealed that 30% of AtSPY targets were also O-GlcNAcylated, indicating that these distinct glycosylations could co-regulate many protein functions. 36740243 9 24 theme targets 1308:1314 arg1 targets 1308:1314 AtSPY targets 1302:1314 AtSPY targets 1302:1314 A comparison with the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome revealed that 30% of AtSPY targets were also O-GlcNAcylated, indicating that these distinct glycosylations could co-regulate many protein functions. 36740243 1 25 theme target 192:197 arg1 activity 207:214 target protein activity 192:214 target protein activity 192:214 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 0 26 theme SPINDLY 0:6 arg1 proteins 46:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins 0:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins 0:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins involved in diverse cellular processes in plants. 36740243 6 27 theme O-fucosylated 850:862 arg1 peptides 864:871 O-fucosylated peptides 850:871 O-fucosylated peptides 850:871 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 8 28 theme microtubule-mediated 1137:1156 arg1 division/growth 1163:1177 microtubule-mediated cell division/growth 1137:1177 microtubule-mediated cell division/growth 1137:1177 Cytoplasmic AtSPY targets were involved in microtubule-mediated cell division/growth and protein folding. 36740243 2 29 theme cytokinin 423:431 arg1 responses 433:441 gibberellin and cytokinin responses 407:441 gibberellin and cytokinin responses 407:441 Previous genetic studies indicate that AtSPY regulates plant development during vegetative and reproductive growth by modulating gibberellin and cytokinin responses. 36740243 7 30 theme DNA 1020:1022 arg1 repair 1024:1029 DNA repair 1020:1029 DNA repair 1020:1029 Most AtSPY targets were nuclear proteins that function in DNA repair, transcription, RNA splicing, and nucleocytoplasmic transport. 36740243 6 31 theme Nicotiana 804:812 arg1 benthamiana 814:824 Nicotiana benthamiana 804:824 Nicotiana benthamiana 804:824 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 2 32 theme plant 333:337 arg1 development 339:349 plant development 333:349 plant development 333:349 Previous genetic studies indicate that AtSPY regulates plant development during vegetative and reproductive growth by modulating gibberellin and cytokinin responses. 36740243 10 33 theme regulatory 1587:1596 arg1 mechanisms 1598:1607 the regulatory mechanisms 1583:1607 the regulatory mechanisms involved 1583:1616 This study unveiled the roles of O-fucosylation in modulating many key nuclear and cytoplasmic proteins and provided a valuable resource for elucidating the regulatory mechanisms involved. 36740243 6 34 from benthamiana 814:824 arg1 targets 752:758 88 SPY targets 745:758 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana 745:824 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 0 35 theme nuclear 22:28 arg1 proteins 46:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins 0:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins 0:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins involved in diverse cellular processes in plants. 36740243 6 36 theme transfer 924:931 arg1 analysis 952:959 electron transfer dissociation-MS/MS analysis 915:959 electron transfer dissociation-MS/MS analysis 915:959 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 3 37 theme abiotic 519:525 arg1 stresses 527:534 biotic and abiotic stresses 508:534 biotic and abiotic stresses 508:534 AtSPY also regulates the circadian clock and plant responses to biotic and abiotic stresses. 36740243 4 38 theme AtSPY 607:611 arg1 role 599:602 the likely role 588:602 the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways 588:679 The pleiotropic phenotypes of spy mutants point to the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways. 36740243 0 39 from processes 84:92 arg1 plants 97:102 plants 97:102 plants 97:102 SPINDLY O-fucosylates nuclear and cytoplasmic proteins involved in diverse cellular processes in plants. 36740243 1 40 theme protein 199:205 arg1 activity 207:214 target protein activity 192:214 target protein activity 192:214 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 0 41 theme cytoplasmic 34:44 arg1 proteins 46:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins 0:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins 0:53 SPINDLY O-fucosylates nuclear and cytoplasmic proteins involved in diverse cellular processes in plants. 36740243 6 42 gly O-fucosylated 850:862 arg1 peptides 864:871 O-fucosylated peptides 850:871 O-fucosylated peptides 850:871 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 3 43 theme circadian 469:477 arg1 clock 479:483 the circadian clock 465:483 the circadian clock 465:483 AtSPY also regulates the circadian clock and plant responses to biotic and abiotic stresses. 36740243 10 44 theme O-fucosylation 1463:1476 arg1 roles 1454:1458 the roles 1450:1458 the roles of O-fucosylation in modulating many key nuclear and cytoplasmic proteins 1450:1532 This study unveiled the roles of O-fucosylation in modulating many key nuclear and cytoplasmic proteins and provided a valuable resource for elucidating the regulatory mechanisms involved. 36740243 3 45 theme biotic 508:513 arg1 stresses 527:534 biotic and abiotic stresses 508:534 biotic and abiotic stresses 508:534 AtSPY also regulates the circadian clock and plant responses to biotic and abiotic stresses. 36740243 9 46 with comparison 1202:1211 arg1 proteome 1272:1279 the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome 1218:1279 the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome 1218:1279 A comparison with the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome revealed that 30% of AtSPY targets were also O-GlcNAcylated, indicating that these distinct glycosylations could co-regulate many protein functions. 36740243 10 47 theme cytoplasmic 1513:1523 arg1 proteins 1525:1532 many key nuclear and cytoplasmic proteins 1492:1532 many key nuclear and cytoplasmic proteins 1492:1532 This study unveiled the roles of O-fucosylation in modulating many key nuclear and cytoplasmic proteins and provided a valuable resource for elucidating the regulatory mechanisms involved. 36740243 9 48 theme published 1222:1230 arg1 proteome 1272:1279 the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome 1218:1279 the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome 1218:1279 A comparison with the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome revealed that 30% of AtSPY targets were also O-GlcNAcylated, indicating that these distinct glycosylations could co-regulate many protein functions. 36740243 6 49 from thaliana 790:797 arg1 targets 752:758 88 SPY targets 745:758 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana 745:824 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 8 50 theme protein 1183:1189 arg1 folding 1191:1197 protein folding 1183:1197 protein folding 1183:1197 Cytoplasmic AtSPY targets were involved in microtubule-mediated cell division/growth and protein folding. 36740243 4 51 theme likely 592:597 arg1 role 599:602 the likely role 588:602 the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways 588:679 The pleiotropic phenotypes of spy mutants point to the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways. 36740243 1 52 theme nucleocytoplasmic 130:146 arg1 SPINDLY 105:111 SPINDLY 105:111 SPINDLY (SPY) 105:117 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 1 52 theme nucleocytoplasmic 130:146 arg1 O-fucosyltransferase 156:175 a novel nucleocytoplasmic protein O-fucosyltransferase 122:175 a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues 122:275 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 9 53 theme O-linked-N-acetylglucosamine 1232:1259 arg1 proteome 1272:1279 the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome 1218:1279 the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome 1218:1279 A comparison with the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome revealed that 30% of AtSPY targets were also O-GlcNAcylated, indicating that these distinct glycosylations could co-regulate many protein functions. 36740243 2 54 theme reproductive 373:384 arg1 growth 386:391 vegetative and reproductive growth 358:391 vegetative and reproductive growth 358:391 Previous genetic studies indicate that AtSPY regulates plant development during vegetative and reproductive growth by modulating gibberellin and cytokinin responses. 36740243 6 55 theme aurantia 887:894 arg1 lectin 896:901 Aleuria aurantia lectin 879:901 Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis 879:959 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 2 56 theme genetic 287:293 arg1 studies 295:301 Previous genetic studies 278:301 Previous genetic studies 278:301 Previous genetic studies indicate that AtSPY regulates plant development during vegetative and reproductive growth by modulating gibberellin and cytokinin responses. 36740243 6 57 theme Arabidopsis 778:788 arg1 thaliana 790:797 Arabidopsis (Arabidopsis thaliana) 765:798 Arabidopsis (Arabidopsis thaliana) 765:798 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 7 58 theme nuclear 986:992 arg1 proteins 994:1001 nuclear proteins 986:1001 nuclear proteins that function in DNA repair, transcription, RNA splicing, and nucleocytoplasmic transport 986:1091 Most AtSPY targets were nuclear proteins that function in DNA repair, transcription, RNA splicing, and nucleocytoplasmic transport. 36740243 4 59 theme diverse 655:661 arg1 pathways 672:679 diverse cellular pathways 655:679 diverse cellular pathways 655:679 The pleiotropic phenotypes of spy mutants point to the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways. 36740243 7 60 theme nucleocytoplasmic 1065:1081 arg1 transport 1083:1091 nucleocytoplasmic transport 1065:1091 nucleocytoplasmic transport 1065:1091 Most AtSPY targets were nuclear proteins that function in DNA repair, transcription, RNA splicing, and nucleocytoplasmic transport. 36740243 6 61 theme Aleuria 879:885 arg1 lectin 896:901 Aleuria aurantia lectin 879:901 Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis 879:959 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 2 62 theme Previous 278:285 arg1 studies 295:301 Previous genetic studies 278:301 Previous genetic studies 278:301 Previous genetic studies indicate that AtSPY regulates plant development during vegetative and reproductive growth by modulating gibberellin and cytokinin responses. 36740243 10 63 theme key 1497:1499 arg1 proteins 1525:1532 many key nuclear and cytoplasmic proteins 1492:1532 many key nuclear and cytoplasmic proteins 1492:1532 This study unveiled the roles of O-fucosylation in modulating many key nuclear and cytoplasmic proteins and provided a valuable resource for elucidating the regulatory mechanisms involved. 36740243 2 64 theme vegetative 358:367 arg1 growth 386:391 vegetative and reproductive growth 358:391 vegetative and reproductive growth 358:391 Previous genetic studies indicate that AtSPY regulates plant development during vegetative and reproductive growth by modulating gibberellin and cytokinin responses. 36740243 7 65 theme AtSPY 967:971 arg1 targets 973:979 Most AtSPY targets 962:979 Most AtSPY targets 962:979 Most AtSPY targets were nuclear proteins that function in DNA repair, transcription, RNA splicing, and nucleocytoplasmic transport. 36740243 0 66 theme cellular 75:82 arg1 processes 84:92 diverse cellular processes 67:92 diverse cellular processes in plants 67:102 SPINDLY O-fucosylates nuclear and cytoplasmic proteins involved in diverse cellular processes in plants. 36740243 10 67 theme many 1492:1495 arg1 proteins 1525:1532 many key nuclear and cytoplasmic proteins 1492:1532 many key nuclear and cytoplasmic proteins 1492:1532 This study unveiled the roles of O-fucosylation in modulating many key nuclear and cytoplasmic proteins and provided a valuable resource for elucidating the regulatory mechanisms involved. 36740243 6 68 theme Arabidopsis 765:775 arg1 thaliana 790:797 Arabidopsis (Arabidopsis thaliana) 765:798 Arabidopsis (Arabidopsis thaliana) 765:798 Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. 36740243 1 69 theme novel 124:128 arg1 SPINDLY 105:111 SPINDLY 105:111 SPINDLY (SPY) 105:117 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 1 69 theme novel 124:128 arg1 O-fucosyltransferase 156:175 a novel nucleocytoplasmic protein O-fucosyltransferase 122:175 a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues 122:275 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 9 70 theme distinct 1364:1371 arg1 glycosylations 1373:1386 these distinct glycosylations 1358:1386 these distinct glycosylations 1358:1386 A comparison with the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome revealed that 30% of AtSPY targets were also O-GlcNAcylated, indicating that these distinct glycosylations could co-regulate many protein functions. 36740243 1 71 theme specific 251:258 arg1 residues 268:275 specific Ser/Thr residues 251:275 specific Ser/Thr residues 251:275 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 36740243 0 72 theme diverse 67:73 arg1 processes 84:92 diverse cellular processes 67:92 diverse cellular processes in plants 67:102 SPINDLY O-fucosylates nuclear and cytoplasmic proteins involved in diverse cellular processes in plants. 36740243 9 73 theme protein 1411:1417 arg1 functions 1419:1427 many protein functions 1406:1427 many protein functions 1406:1427 A comparison with the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome revealed that 30% of AtSPY targets were also O-GlcNAcylated, indicating that these distinct glycosylations could co-regulate many protein functions. 36740243 4 74 theme cellular 663:670 arg1 pathways 672:679 diverse cellular pathways 655:679 diverse cellular pathways 655:679 The pleiotropic phenotypes of spy mutants point to the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways. 36740243 2 75 theme gibberellin 407:417 arg1 responses 433:441 gibberellin and cytokinin responses 407:441 gibberellin and cytokinin responses 407:441 Previous genetic studies indicate that AtSPY regulates plant development during vegetative and reproductive growth by modulating gibberellin and cytokinin responses. 36740243 1 76 theme Ser/Thr 260:266 arg1 residues 268:275 specific Ser/Thr residues 251:275 specific Ser/Thr residues 251:275 SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. 34927362 12 0 theme down 1752:1755 arg1 regulation 1757:1766 down regulation 1752:1766 down regulation of FXa activity by inhibitors 1752:1796 In plasma-based assays, a modest decrease in FX activation rate appeared to knock down the procoagulant response even when down regulation of FXa activity by inhibitors was reduced. 34927362 10 1 theme enhanced 1481:1488 arg1 activity 1503:1510 enhanced procoagulant activity 1481:1510 enhanced procoagulant activity 1481:1510 When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants. 34927362 10 2 theme activated 1529:1537 arg1 variants 1543:1550 activated FXa variants 1529:1550 activated FXa variants 1529:1550 When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants. 34927362 9 3 theme full-length 1135:1145 arg1 TFPI 1147:1150 full-length TFPI 1135:1150 full-length TFPI of these FXa variants 1135:1172 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 12 4 theme procoagulant 1720:1731 arg1 response 1733:1740 the procoagulant response 1716:1740 the procoagulant response 1716:1740 In plasma-based assays, a modest decrease in FX activation rate appeared to knock down the procoagulant response even when down regulation of FXa activity by inhibitors was reduced. 34927362 2 5 theme form 335:338 arg1 regulation 298:307 the regulation 294:307 the regulation of the zymogen and active form of FX 294:344 OBJECTIVES To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX. 34927362 11 6 theme regulation 1617:1626 arg1 aspects 1603:1609 all aspects 1599:1609 all aspects of FX regulation 1599:1626 CONCLUSION The autolysis loop participates in all aspects of FX regulation. 34927362 5 7 theme in 585:586 arg1 generation 603:612 in vitro thrombin generation 585:612 The in vitro thrombin generation potential of the FX variants 581:641 The in vitro thrombin generation potential of the FX variants was evaluated in FX-depleted plasma. 34927362 10 8 theme zymogen 1370:1376 arg1 form 1378:1381 zymogen form 1370:1381 zymogen form 1370:1381 When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants. 34927362 7 9 theme Prothrombin 810:820 arg1 activation 822:831 Prothrombin activation 810:831 Prothrombin activation 810:831 Prothrombin activation was, however, recovered in presence of cofactor factor Va (FVa) despite a reduced prothrombinase assembly. 34927362 5 10 theme thrombin 594:601 arg1 generation 603:612 in vitro thrombin generation 585:612 The in vitro thrombin generation potential of the FX variants 581:641 The in vitro thrombin generation potential of the FX variants was evaluated in FX-depleted plasma. 34927362 9 11 theme FXa 1161:1163 arg1 variants 1165:1172 these FXa variants 1155:1172 these FXa variants 1155:1172 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 2 12 theme FX 273:274 arg1 loop 286:289 the FX autolysis loop 269:289 the FX autolysis loop 269:289 OBJECTIVES To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX. 34927362 8 13 theme position-specific 975:991 arg1 effects 993:999 position-specific effects 975:999 position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII) 975:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 5 14 theme FX-depleted 660:670 arg1 plasma 672:677 FX-depleted plasma 660:677 FX-depleted plasma 660:677 The in vitro thrombin generation potential of the FX variants was evaluated in FX-depleted plasma. 34927362 3 15 theme N-linked 375:382 arg1 glycosylations 384:397 novel N-linked glycosylations 369:397 novel N-linked glycosylations 369:397 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 4 16 theme pure 558:561 arg1 assays 573:578 pure component assays 558:578 pure component assays 558:578 The activity and inhibition of recombinant FX variants was quantified in pure component assays. 34927362 5 17 theme variants 634:641 arg1 potential 614:622 The in vitro thrombin generation potential 581:622 The in vitro thrombin generation potential of the FX variants 581:641 The in vitro thrombin generation potential of the FX variants was evaluated in FX-depleted plasma. 34927362 2 18 from role 261:264 arg1 regulation 298:307 the regulation 294:307 the regulation of the zymogen and active form of FX 294:344 OBJECTIVES To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX. 34927362 9 19 theme ATIII 1216:1220 arg1 inhibition 1222:1231 ATIII inhibition 1216:1231 ATIII inhibition in the presence of the heparin-analog Fondaparinux 1216:1282 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 1 20 theme factor 127:132 arg1 FX 137:138 FX 137:138 FX 137:138 BACKGROUND The regulation of factor X (FX) is critical to maintain the balance between blood coagulation and fluidity. 34927362 1 20 theme factor 127:132 arg1 X 134:134 factor X 127:134 factor X (FX) 127:139 BACKGROUND The regulation of factor X (FX) is critical to maintain the balance between blood coagulation and fluidity. 34927362 0 21 from role 15:18 arg1 regulation 49:58 the regulation 45:58 the regulation of factor X upon hemostatic response 45:95 The functional role of the autolysis loop in the regulation of factor X upon hemostatic response. 34927362 7 22 theme reduced 907:913 arg1 assembly 930:937 a reduced prothrombinase assembly 905:937 a reduced prothrombinase assembly 905:937 Prothrombin activation was, however, recovered in presence of cofactor factor Va (FVa) despite a reduced prothrombinase assembly. 34927362 12 23 theme modest 1655:1660 arg1 decrease 1662:1669 a modest decrease 1653:1669 a modest decrease in FX activation rate 1653:1691 In plasma-based assays, a modest decrease in FX activation rate appeared to knock down the procoagulant response even when down regulation of FXa activity by inhibitors was reduced. 34927362 0 24 theme X 70:70 arg1 regulation 49:58 the regulation 45:58 the regulation of factor X upon hemostatic response 45:95 The functional role of the autolysis loop in the regulation of factor X upon hemostatic response. 34927362 9 25 dep 15-fold 1316:1322 arg1 to 1313:1314 to 1313:1314 to 1313:1314 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 10 26 theme thrombin 1418:1425 arg1 activity 1438:1445 reduced thrombin generation activity 1410:1445 reduced thrombin generation activity relative to wild-type FX 1410:1470 When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants. 34927362 12 27 theme activation 1677:1686 arg1 rate 1688:1691 FX activation rate 1674:1691 FX activation rate 1674:1691 In plasma-based assays, a modest decrease in FX activation rate appeared to knock down the procoagulant response even when down regulation of FXa activity by inhibitors was reduced. 34927362 2 28 theme FX 343:344 arg1 zymogen 316:322 zymogen 316:322 zymogen 316:322 OBJECTIVES To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX. 34927362 2 28 theme FX 343:344 arg1 form 335:338 active form 328:338 active form 328:338 OBJECTIVES To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX. 34927362 0 29 theme hemostatic 77:86 arg1 response 88:95 hemostatic response 77:95 hemostatic response 77:95 The functional role of the autolysis loop in the regulation of factor X upon hemostatic response. 34927362 12 30 theme plasma-based 1632:1643 arg1 assays 1645:1650 plasma-based assays 1632:1650 plasma-based assays 1632:1650 In plasma-based assays, a modest decrease in FX activation rate appeared to knock down the procoagulant response even when down regulation of FXa activity by inhibitors was reduced. 34927362 3 31 theme novel 369:373 arg1 glycosylations 384:397 novel N-linked glycosylations 369:397 novel N-linked glycosylations 369:397 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 9 32 theme Fondaparinux 1271:1282 arg1 presence 1240:1247 the presence 1236:1247 the presence of the heparin-analog Fondaparinux 1236:1282 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 7 33 theme Va 888:889 arg1 presence 860:867 presence 860:867 presence of cofactor factor Va (FVa) 860:895 Prothrombin activation was, however, recovered in presence of cofactor factor Va (FVa) despite a reduced prothrombinase assembly. 34927362 2 34 theme zymogen 316:322 arg1 regulation 298:307 the regulation 294:307 the regulation of the zymogen and active form of FX 294:344 OBJECTIVES To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX. 34927362 3 35 theme loop 422:425 arg1 residues 436:443 the surface-exposed loop spanning residues 143-150 402:451 the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX 402:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 35 theme loop 422:425 arg1 numbering 467:475 chymotrypsin numbering 454:475 chymotrypsin numbering 454:475 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 35 theme loop 422:425 arg1 FX 481:482 FX 481:482 FX 481:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 8 36 theme tissue 1045:1050 arg1 TFPI 1078:1081 TFPI 1078:1081 TFPI 1078:1081 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 36 theme tissue 1045:1050 arg1 inhibitor 1067:1075 tissue factor pathway inhibitor 1045:1075 tissue factor pathway inhibitor (TFPI) 1045:1082 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 36 theme tissue 1045:1050 arg1 inhibitors 1033:1042 two FXa inhibitors 1025:1042 two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII) 1025:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 4 37 theme recombinant 516:526 arg1 variants 531:538 recombinant FX variants 516:538 recombinant FX variants 516:538 The activity and inhibition of recombinant FX variants was quantified in pure component assays. 34927362 8 38 theme pathway 1059:1065 arg1 TFPI 1078:1081 TFPI 1078:1081 TFPI 1078:1081 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 38 theme pathway 1059:1065 arg1 inhibitor 1067:1075 tissue factor pathway inhibitor 1045:1075 tissue factor pathway inhibitor (TFPI) 1045:1082 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 38 theme pathway 1059:1065 arg1 inhibitors 1033:1042 two FXa inhibitors 1025:1042 two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII) 1025:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 12 39 theme FXa 1771:1773 arg1 activity 1775:1782 FXa activity 1771:1782 FXa activity 1771:1782 In plasma-based assays, a modest decrease in FX activation rate appeared to knock down the procoagulant response even when down regulation of FXa activity by inhibitors was reduced. 34927362 0 40 theme loop 37:40 arg1 role 15:18 The functional role 0:18 The functional role of the autolysis loop in the regulation of factor X upon hemostatic response 0:95 The functional role of the autolysis loop in the regulation of factor X upon hemostatic response. 34927362 8 41 with interaction 1008:1018 arg1 antithrombin 1088:1099 antithrombin 1088:1099 antithrombin (ATIII) 1088:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 41 with interaction 1008:1018 arg1 inhibitor 1067:1075 tissue factor pathway inhibitor 1045:1075 tissue factor pathway inhibitor (TFPI) 1045:1082 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 41 with interaction 1008:1018 arg1 inhibitors 1033:1042 two FXa inhibitors 1025:1042 two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII) 1025:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 7 42 theme factor 881:886 arg1 FVa 892:894 FVa 892:894 FVa 892:894 Prothrombin activation was, however, recovered in presence of cofactor factor Va (FVa) despite a reduced prothrombinase assembly. 34927362 7 42 theme factor 881:886 arg1 Va 888:889 cofactor factor Va 872:889 cofactor factor Va (FVa) 872:895 Prothrombin activation was, however, recovered in presence of cofactor factor Va (FVa) despite a reduced prothrombinase assembly. 34927362 6 43 theme steric 791:796 arg1 hinderance 798:807 steric hinderance 791:807 steric hinderance 791:807 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. 34927362 9 44 dep 7- 1191:1192 arg1 to 1194:1195 to 1194:1195 to 1194:1195 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 6 45 theme factor 692:697 arg1 FVIIa 705:709 FVIIa 705:709 FVIIa 705:709 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. 34927362 6 45 theme factor 692:697 arg1 VIIa 699:702 factor VIIa 692:702 factor VIIa (FVIIa) 692:710 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. 34927362 9 46 dep increased 1178:1186 arg1 whereas 1208:1214 whereas 1208:1214 whereas 1208:1214 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 10 47 theme procoagulant 1490:1501 arg1 activity 1503:1510 enhanced procoagulant activity 1481:1510 enhanced procoagulant activity 1481:1510 When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants. 34927362 11 48 theme FX 1614:1615 arg1 regulation 1617:1626 FX regulation 1614:1626 FX regulation 1614:1626 CONCLUSION The autolysis loop participates in all aspects of FX regulation. 34927362 5 49 theme generation 603:612 arg1 potential 614:622 The in vitro thrombin generation potential 581:622 The in vitro thrombin generation potential of the FX variants 581:641 The in vitro thrombin generation potential of the FX variants was evaluated in FX-depleted plasma. 34927362 9 50 dep increased 1297:1305 arg1 compared 1324:1331 compared 1324:1331 compared with wild-type 1324:1346 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 4 51 theme variants 531:538 arg1 activity 489:496 activity 489:496 activity 489:496 The activity and inhibition of recombinant FX variants was quantified in pure component assays. 34927362 4 51 theme variants 531:538 arg1 inhibition 502:511 inhibition 502:511 inhibition 502:511 The activity and inhibition of recombinant FX variants was quantified in pure component assays. 34927362 10 52 theme FXa 1539:1541 arg1 variants 1543:1550 activated FXa variants 1529:1550 activated FXa variants 1529:1550 When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants. 34927362 8 53 theme introduced 944:953 arg1 N-glycans 955:963 The introduced N-glycans 940:963 The introduced N-glycans 940:963 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 3 54 link N-linked 375:382 arg1 glycosylations 384:397 novel N-linked glycosylations 369:397 novel N-linked glycosylations 369:397 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 11 55 dep CONCLUSION 1553:1562 arg1 participates 1583:1594 participates 1583:1594 participates in all aspects of FX regulation 1583:1626 CONCLUSION The autolysis loop participates in all aspects of FX regulation. 34927362 6 56 theme prothrombin 736:746 arg1 RESULTS 680:686 RESULTS 680:686 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation 680:757 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. 34927362 6 56 theme prothrombin 736:746 arg1 activation 748:757 prothrombin activation 736:757 prothrombin activation 736:757 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. 34927362 2 57 theme autolysis 276:284 arg1 loop 286:289 the FX autolysis loop 269:289 the FX autolysis loop 269:289 OBJECTIVES To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX. 34927362 9 58 theme variants 1165:1172 arg1 TFPI 1147:1150 full-length TFPI 1135:1150 full-length TFPI of these FXa variants 1135:1172 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 9 59 from inhibition 1222:1231 arg1 presence 1240:1247 the presence 1236:1247 the presence of the heparin-analog Fondaparinux 1236:1282 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 12 60 from decrease 1662:1669 arg1 rate 1688:1691 FX activation rate 1674:1691 FX activation rate 1674:1691 In plasma-based assays, a modest decrease in FX activation rate appeared to knock down the procoagulant response even when down regulation of FXa activity by inhibitors was reduced. 34927362 12 61 theme FX 1674:1675 arg1 rate 1688:1691 FX activation rate 1674:1691 FX activation rate 1674:1691 In plasma-based assays, a modest decrease in FX activation rate appeared to knock down the procoagulant response even when down regulation of FXa activity by inhibitors was reduced. 34927362 0 62 theme factor 63:68 arg1 X 70:70 factor X 63:70 factor X 63:70 The functional role of the autolysis loop in the regulation of factor X upon hemostatic response. 34927362 4 63 dep activity 489:496 arg1 The 485:487 The 485:487 The 485:487 The activity and inhibition of recombinant FX variants was quantified in pure component assays. 34927362 1 64 theme X 134:134 arg1 regulation 113:122 The regulation 109:122 The regulation of factor X (FX) 109:139 BACKGROUND The regulation of factor X (FX) is critical to maintain the balance between blood coagulation and fluidity. 34927362 1 64 theme X 134:134 arg1 critical 144:151 critical 144:151 critical 144:151 BACKGROUND The regulation of factor X (FX) is critical to maintain the balance between blood coagulation and fluidity. 34927362 7 65 theme prothrombinase 915:928 arg1 assembly 930:937 a reduced prothrombinase assembly 905:937 a reduced prothrombinase assembly 905:937 Prothrombin activation was, however, recovered in presence of cofactor factor Va (FVa) despite a reduced prothrombinase assembly. 34927362 2 66 dep zymogen 316:322 arg1 the 312:314 the 312:314 the 312:314 OBJECTIVES To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX. 34927362 8 67 theme FXa 1029:1031 arg1 antithrombin 1088:1099 antithrombin 1088:1099 antithrombin (ATIII) 1088:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 67 theme FXa 1029:1031 arg1 inhibitor 1067:1075 tissue factor pathway inhibitor 1045:1075 tissue factor pathway inhibitor (TFPI) 1045:1082 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 67 theme FXa 1029:1031 arg1 inhibitors 1033:1042 two FXa inhibitors 1025:1042 two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII) 1025:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 10 68 theme reduced 1410:1416 arg1 activity 1438:1445 reduced thrombin generation activity 1410:1445 reduced thrombin generation activity relative to wild-type FX 1410:1470 When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants. 34927362 1 69 dep BACKGROUND 98:107 arg1 critical 144:151 critical 144:151 critical 144:151 BACKGROUND The regulation of factor X (FX) is critical to maintain the balance between blood coagulation and fluidity. 34927362 1 69 dep BACKGROUND 98:107 arg1 regulation 113:122 The regulation 109:122 The regulation of factor X (FX) 109:139 BACKGROUND The regulation of factor X (FX) is critical to maintain the balance between blood coagulation and fluidity. 34927362 0 70 theme functional 4:13 arg1 role 15:18 The functional role 0:18 The functional role of the autolysis loop in the regulation of factor X upon hemostatic response 0:95 The functional role of the autolysis loop in the regulation of factor X upon hemostatic response. 34927362 9 71 theme heparin-analog 1256:1269 arg1 Fondaparinux 1271:1282 the heparin-analog Fondaparinux 1252:1282 the heparin-analog Fondaparinux 1252:1282 Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, whereas ATIII inhibition in the presence of the heparin-analog Fondaparinux was modestly increased by 2- to 15-fold compared with wild-type. 34927362 2 72 theme active 328:333 arg1 form 335:338 active form 328:338 active form 328:338 OBJECTIVES To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX. 34927362 8 73 theme factor 1052:1057 arg1 TFPI 1078:1081 TFPI 1078:1081 TFPI 1078:1081 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 73 theme factor 1052:1057 arg1 inhibitor 1067:1075 tissue factor pathway inhibitor 1045:1075 tissue factor pathway inhibitor (TFPI) 1045:1082 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 73 theme factor 1052:1057 arg1 inhibitors 1033:1042 two FXa inhibitors 1025:1042 two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII) 1025:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 4 74 theme FX 528:529 arg1 variants 531:538 recombinant FX variants 516:538 recombinant FX variants 516:538 The activity and inhibition of recombinant FX variants was quantified in pure component assays. 34927362 10 75 theme relative 1447:1454 arg1 activity 1438:1445 reduced thrombin generation activity 1410:1445 reduced thrombin generation activity relative to wild-type FX 1410:1470 When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants. 34927362 3 76 theme spanning 427:434 arg1 residues 436:443 the surface-exposed loop spanning residues 143-150 402:451 the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX 402:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 76 theme spanning 427:434 arg1 numbering 467:475 chymotrypsin numbering 454:475 chymotrypsin numbering 454:475 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 76 theme spanning 427:434 arg1 FX 481:482 FX 481:482 FX 481:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 0 77 theme autolysis 27:35 arg1 loop 37:40 the autolysis loop 23:40 the autolysis loop 23:40 The functional role of the autolysis loop in the regulation of factor X upon hemostatic response. 34927362 10 78 theme generation 1427:1436 arg1 activity 1438:1445 reduced thrombin generation activity 1410:1445 reduced thrombin generation activity relative to wild-type FX 1410:1470 When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants. 34927362 6 79 theme -mediated 711:719 arg1 activation 721:730 activation 721:730 activation 721:730 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. 34927362 6 79 theme -mediated 711:719 arg1 RESULTS 680:686 RESULTS 680:686 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation 680:757 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. 34927362 3 80 theme surface-exposed 406:420 arg1 residues 436:443 the surface-exposed loop spanning residues 143-150 402:451 the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX 402:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 80 theme surface-exposed 406:420 arg1 numbering 467:475 chymotrypsin numbering 454:475 chymotrypsin numbering 454:475 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 80 theme surface-exposed 406:420 arg1 FX 481:482 FX 481:482 FX 481:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 5 81 dep in 585:586 arg1 vitro 588:592 vitro 588:592 vitro 588:592 The in vitro thrombin generation potential of the FX variants was evaluated in FX-depleted plasma. 34927362 3 82 dep METHODS 347:353 arg1 introduced 358:367 introduced 358:367 introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX 358:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 83 theme chymotrypsin 454:465 arg1 residues 436:443 the surface-exposed loop spanning residues 143-150 402:451 the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX 402:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 83 theme chymotrypsin 454:465 arg1 numbering 467:475 chymotrypsin numbering 454:475 chymotrypsin numbering 454:475 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 83 theme chymotrypsin 454:465 arg1 FX 481:482 FX 481:482 FX 481:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 7 84 theme cofactor 872:879 arg1 FVa 892:894 FVa 892:894 FVa 892:894 Prothrombin activation was, however, recovered in presence of cofactor factor Va (FVa) despite a reduced prothrombinase assembly. 34927362 7 84 theme cofactor 872:879 arg1 Va 888:889 cofactor factor Va 872:889 cofactor factor Va (FVa) 872:895 Prothrombin activation was, however, recovered in presence of cofactor factor Va (FVa) despite a reduced prothrombinase assembly. 34927362 12 85 theme activity 1775:1782 arg1 regulation 1757:1766 down regulation 1752:1766 down regulation of FXa activity by inhibitors 1752:1796 In plasma-based assays, a modest decrease in FX activation rate appeared to knock down the procoagulant response even when down regulation of FXa activity by inhibitors was reduced. 34927362 6 86 dep RESULTS 680:686 arg1 activation 721:730 activation 721:730 activation 721:730 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. 34927362 6 86 dep RESULTS 680:686 arg1 activation 748:757 prothrombin activation 736:757 prothrombin activation 736:757 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. 34927362 6 86 dep RESULTS 680:686 arg1 RESULTS 680:686 RESULTS 680:686 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation 680:757 RESULTS The factor VIIa (FVIIa)-mediated activation and prothrombin activation was reduced, presumably through steric hinderance. 34927362 4 87 theme component 563:571 arg1 assays 573:578 pure component assays 558:578 pure component assays 558:578 The activity and inhibition of recombinant FX variants was quantified in pure component assays. 34927362 10 88 theme wild-type 1459:1467 arg1 FX 1469:1470 wild-type FX 1459:1470 wild-type FX 1459:1470 When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FXa variants. 34927362 2 89 theme loop 286:289 arg1 role 261:264 the role 257:264 the role of the FX autolysis loop in the regulation of the zymogen and active form of FX 257:344 OBJECTIVES To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX. 34927362 1 90 theme blood 185:189 arg1 coagulation 191:201 blood coagulation 185:201 blood coagulation 185:201 BACKGROUND The regulation of factor X (FX) is critical to maintain the balance between blood coagulation and fluidity. 34927362 8 91 from effects 993:999 arg1 interaction 1008:1018 the interaction 1004:1018 the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII) 1004:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 92 dep inhibitors 1033:1042 arg1 ATIII 1102:1106 ATIII 1102:1106 ATIII 1102:1106 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 92 dep inhibitors 1033:1042 arg1 TFPI 1078:1081 TFPI 1078:1081 TFPI 1078:1081 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 92 dep inhibitors 1033:1042 arg1 antithrombin 1088:1099 antithrombin 1088:1099 antithrombin (ATIII) 1088:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 92 dep inhibitors 1033:1042 arg1 inhibitor 1067:1075 tissue factor pathway inhibitor 1045:1075 tissue factor pathway inhibitor (TFPI) 1045:1082 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 8 92 dep inhibitors 1033:1042 arg1 inhibitors 1033:1042 two FXa inhibitors 1025:1042 two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII) 1025:1107 The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). 34927362 11 93 theme autolysis 1568:1576 arg1 loop 1578:1581 The autolysis loop 1564:1581 The autolysis loop 1564:1581 CONCLUSION The autolysis loop participates in all aspects of FX regulation. 34927362 3 94 theme FX 481:482 arg1 residues 436:443 the surface-exposed loop spanning residues 143-150 402:451 the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX 402:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 94 theme FX 481:482 arg1 numbering 467:475 chymotrypsin numbering 454:475 chymotrypsin numbering 454:475 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 34927362 3 94 theme FX 481:482 arg1 FX 481:482 FX 481:482 FX 481:482 METHODS We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. 37152991 10 0 theme underlying 1843:1852 arg1 pathophysiology 1854:1868 the underlying pathophysiology 1839:1868 the underlying pathophysiology of the phenotypic heterogeneity 1839:1900 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 3 1 theme Whole-exome 489:499 arg1 WES 513:515 WES 513:515 WES 513:515 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 3 1 theme Whole-exome 489:499 arg1 sequencing 501:510 Whole-exome sequencing 489:510 Whole-exome sequencing (WES) 489:516 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 7 2 from hypoglycosylation 1168:1184 arg1 patients 1189:1196 patients 1189:1196 patients with CDG 1189:1205 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 8 3 theme homozygous 1313:1322 arg1 variants 1349:1356 homozygous or compound heterozygous variants 1313:1356 homozygous or compound heterozygous variants of DMP2 gene 1313:1369 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 3 4 theme creatine 688:695 arg1 kinase 697:702 increased serum creatine kinase 672:702 increased serum creatine kinase 672:702 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 7 5 with patients 1189:1196 arg1 CDG 1203:1205 CDG 1203:1205 CDG 1203:1205 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 3 6 theme increased 672:680 arg1 kinase 697:702 increased serum creatine kinase 672:702 increased serum creatine kinase 672:702 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 0 7 with siblings 83:90 arg1 impairment 115:124 mild intellectual impairment 97:124 mild intellectual impairment 97:124 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 3 8 with DPM2-CDG 592:599 arg1 disability 645:654 mild intellectual disability 627:654 mild intellectual disability 627:654 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 3 8 with DPM2-CDG 592:599 arg1 delay 620:624 developmental delay 606:624 developmental delay 606:624 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 3 8 with DPM2-CDG 592:599 arg1 hypotonia 657:665 hypotonia 657:665 hypotonia 657:665 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 3 8 with DPM2-CDG 592:599 arg1 kinase 697:702 increased serum creatine kinase 672:702 increased serum creatine kinase 672:702 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 6 9 theme DPM2 911:914 arg1 exon 901:904 exon 4 901:906 exon 4 of DPM2 (NM_003863) 901:926 Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). 37152991 8 10 contain had 1454:1456 arg2 symptoms 1479:1486 more severe clinical symptoms 1458:1486 more severe clinical symptoms 1458:1486 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 8 10 contain had 1454:1456 arg1 patients 1387:1394 patients 1387:1394 patients with variants within the region encoding the first domain 1387:1452 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 0 11 theme intellectual 102:113 arg1 impairment 115:124 mild intellectual impairment 97:124 mild intellectual impairment 97:124 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 5 12 theme In 803:804 arg1 study 823:827 In vitro functional study 803:827 In vitro functional study 803:827 In vitro functional study was performed. 37152991 7 13 from decrease 1123:1130 arg1 ICAM1 1135:1139 ICAM1 1135:1139 ICAM1 1135:1139 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 7 13 from decrease 1123:1130 arg1 biomarker 1154:1162 a universal biomarker 1142:1162 a universal biomarker for hypoglycosylation in patients with CDG 1142:1205 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 10 14 theme different 1746:1754 arg1 variants 1761:1768 different DPM2 variants 1746:1768 different DPM2 variants 1746:1768 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 5 15 theme functional 812:821 arg1 study 823:827 In vitro functional study 803:827 In vitro functional study 803:827 In vitro functional study was performed. 37152991 10 16 theme variant 1653:1659 arg1 spectrum 1661:1668 the variant spectrum 1649:1668 the variant spectrum of DPM2 gene 1649:1681 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 6 17 theme exome 952:956 arg1 WES 970:972 WES 970:972 WES 970:972 Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). 37152991 6 17 theme exome 952:956 arg1 sequencing 958:967 whole exome sequencing 946:967 whole exome sequencing (WES) 946:973 Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). 37152991 0 18 theme DPM2 58:61 arg1 gene 63:66 DPM2 gene 58:66 DPM2 gene in two Chinese siblings with mild intellectual impairment 58:124 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 3 19 theme mild 579:582 arg1 form 584:587 a mild form 577:587 a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase 577:702 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 1 20 theme Congenital 141:150 arg1 CDGs 180:183 CDGs 180:183 CDGs 180:183 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 20 theme Congenital 141:150 arg1 group 218:222 a genetically heterogeneous group 190:222 a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation 190:294 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 20 theme Congenital 141:150 arg1 Introduction 127:138 Introduction 127:138 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 127:295 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 20 theme Congenital 141:150 arg1 disorders 152:160 Congenital disorders 141:160 Congenital disorders of glycosylation (CDGs) 141:184 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 20 theme Congenital 141:150 arg1 disorders 237:245 metabolic disorders 227:245 metabolic disorders caused by abnormal protein or lpid glycosylation 227:294 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 8 21 contain carrying 1304:1311 arg1 patients 1295:1302 the 4 previously reported patients 1269:1302 the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene 1269:1369 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 8 21 contain carrying 1304:1311 arg2 variants 1349:1356 homozygous or compound heterozygous variants 1313:1356 homozygous or compound heterozygous variants of DMP2 gene 1313:1369 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 0 22 from characterization 19:34 arg1 gene 63:66 DPM2 gene 58:66 DPM2 gene in two Chinese siblings with mild intellectual impairment 58:124 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 10 23 theme further 1798:1804 arg1 studies 1817:1823 further functional studies 1798:1823 further functional studies 1798:1823 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 0 24 from Identification 0:13 arg1 gene 63:66 DPM2 gene 58:66 DPM2 gene in two Chinese siblings with mild intellectual impairment 58:124 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 0 25 theme Chinese 75:81 arg1 siblings 83:90 two Chinese siblings 71:90 two Chinese siblings with mild intellectual impairment 71:124 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 0 26 from variation 45:53 arg1 gene 63:66 DPM2 gene 58:66 DPM2 gene in two Chinese siblings with mild intellectual impairment 58:124 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 0 27 theme new 41:43 arg1 variation 45:53 a new variation 39:53 a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment 39:124 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 8 28 theme clinical 1470:1477 arg1 symptoms 1479:1486 more severe clinical symptoms 1458:1486 more severe clinical symptoms 1458:1486 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 4 29 theme Sanger 705:710 arg1 sequencing 712:721 Sanger sequencing 705:721 Sanger sequencing 705:721 Sanger sequencing was used to validate the variants identified in the siblings and their parents. 37152991 8 30 theme compound 1327:1334 arg1 variants 1349:1356 homozygous or compound heterozygous variants 1313:1356 homozygous or compound heterozygous variants of DMP2 gene 1313:1369 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 7 31 theme N-linked 1228:1235 arg1 glycosylation 1237:1249 abnormal N-linked glycosylation 1219:1249 abnormal N-linked glycosylation 1219:1249 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 8 32 theme DMP2 1361:1364 arg1 gene 1366:1369 DMP2 gene 1361:1369 DMP2 gene 1361:1369 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 10 33 theme phenotypic 1877:1886 arg1 heterogeneity 1888:1900 the phenotypic heterogeneity 1873:1900 the phenotypic heterogeneity 1873:1900 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 2 34 theme complex 337:343 arg1 subunit 309:315 one subunit 305:315 one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation 305:420 DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported. 37152991 7 35 theme DPM2 1070:1073 arg1 protein 1075:1081 DPM2 protein 1070:1081 DPM2 protein 1070:1081 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 8 36 theme second 1524:1529 arg1 domain 1531:1536 the second domain 1520:1536 the second domain 1520:1536 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 8 37 with patients 1387:1394 arg1 variants 1401:1408 variants 1401:1408 variants within the region encoding the first domain 1401:1452 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 9 38 theme genotype-phenotype 1559:1576 arg1 relationship 1578:1589 the actual genotype-phenotype relationship 1548:1589 the actual genotype-phenotype relationship 1548:1589 However, the actual genotype-phenotype relationship needs more study. 37152991 2 39 from enzyme 398:403 arg1 glycosylation 408:420 glycosylation 408:420 glycosylation 408:420 DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported. 37152991 7 40 dep In 976:977 arg1 vitro 979:983 vitro 979:983 vitro 979:983 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 3 41 theme mild 627:630 arg1 disability 645:654 mild intellectual disability 627:654 mild intellectual disability 627:654 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 10 42 theme gene 1678:1681 arg1 spectrum 1661:1668 the variant spectrum 1649:1668 the variant spectrum of DPM2 gene 1649:1681 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 1 43 theme metabolic 227:235 arg1 disorders 237:245 metabolic disorders 227:245 metabolic disorders caused by abnormal protein or lpid glycosylation 227:294 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 7 44 theme significant 1111:1121 arg1 decrease 1123:1130 a significant decrease 1109:1130 a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG 1109:1205 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 7 45 theme expression 1050:1059 arg1 level 1061:1065 the expression level 1046:1065 the expression level of DPM2 protein 1046:1081 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 2 46 theme dolichol-phosphatemannose 349:373 arg1 enzyme 398:403 a key enzyme 392:403 a key enzyme in glycosylation 392:420 DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported. 37152991 2 46 theme dolichol-phosphatemannose 349:373 arg1 DPMS 385:388 DPMS 385:388 DPMS 385:388 DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported. 37152991 2 46 theme dolichol-phosphatemannose 349:373 arg1 synthase 375:382 dolichol-phosphatemannose synthase 349:382 dolichol-phosphatemannose synthase (DPMS) 349:389 DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported. 37152991 7 47 link N-linked 1228:1235 arg1 glycosylation 1237:1249 abnormal N-linked glycosylation 1219:1249 abnormal N-linked glycosylation 1219:1249 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 3 48 contain having 552:557 arg2 siblings 563:570 two siblings 559:570 two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase 559:702 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 3 48 contain having 552:557 arg1 family 545:550 a Chinese family 535:550 a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase 535:702 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 1 49 theme abnormal 257:264 arg1 protein 266:272 abnormal protein 257:272 abnormal protein 257:272 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 6 50 theme homozygous 855:864 arg1 c.197G>A 876:883 c.197G>A 876:883 c.197G>A (p.Gly66Glu) 876:896 Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). 37152991 6 50 theme homozygous 855:864 arg1 mutation 866:873 A homozygous mutation 853:873 A homozygous mutation 853:873 Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). 37152991 10 51 theme heterogeneity 1888:1900 arg1 pathophysiology 1854:1868 the underlying pathophysiology 1839:1868 the underlying pathophysiology of the phenotypic heterogeneity 1839:1900 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 1 52 theme glycosylation 165:177 arg1 CDGs 180:183 CDGs 180:183 CDGs 180:183 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 52 theme glycosylation 165:177 arg1 group 218:222 a genetically heterogeneous group 190:222 a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation 190:294 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 52 theme glycosylation 165:177 arg1 Introduction 127:138 Introduction 127:138 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 127:295 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 52 theme glycosylation 165:177 arg1 disorders 152:160 Congenital disorders 141:160 Congenital disorders of glycosylation (CDGs) 141:184 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 52 theme glycosylation 165:177 arg1 disorders 237:245 metabolic disorders 227:245 metabolic disorders caused by abnormal protein or lpid glycosylation 227:294 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 0 53 theme variation 45:53 arg1 characterization 19:34 characterization 19:34 characterization 19:34 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 0 53 theme variation 45:53 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 3 54 theme serum 682:686 arg1 kinase 697:702 increased serum creatine kinase 672:702 increased serum creatine kinase 672:702 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 3 55 theme Chinese 537:543 arg1 family 545:550 a Chinese family 535:550 a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase 535:702 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 8 56 dep homozygous 1313:1322 arg1 heterozygous 1336:1347 heterozygous 1336:1347 heterozygous 1336:1347 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 7 57 theme functional 985:994 arg1 analysis 996:1003 In vitro functional analysis 976:1003 In vitro functional analysis 976:1003 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 10 58 theme different 1708:1716 arg1 phenotypes 1718:1727 the different phenotypes 1704:1727 the different phenotypes in patients with different DPM2 variants 1704:1768 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 7 59 theme In 976:977 arg1 analysis 996:1003 In vitro functional analysis 976:1003 In vitro functional analysis 976:1003 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 10 60 theme DPM2 1756:1759 arg1 variants 1761:1768 different DPM2 variants 1746:1768 different DPM2 variants 1746:1768 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 0 61 from gene 63:66 arg1 characterization 19:34 characterization 19:34 characterization 19:34 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 0 61 from gene 63:66 arg1 siblings 83:90 two Chinese siblings 71:90 two Chinese siblings with mild intellectual impairment 71:124 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 0 61 from gene 63:66 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 10 62 with patients 1732:1739 arg1 variants 1761:1768 different DPM2 variants 1746:1768 different DPM2 variants 1746:1768 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 7 63 theme universal 1144:1152 arg1 ICAM1 1135:1139 ICAM1 1135:1139 ICAM1 1135:1139 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 7 63 theme universal 1144:1152 arg1 biomarker 1154:1162 a universal biomarker 1142:1162 a universal biomarker for hypoglycosylation in patients with CDG 1142:1205 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 2 64 with patients 437:444 arg1 DPM2-CDG 451:458 DPM2-CDG 451:458 DPM2-CDG 451:458 DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported. 37152991 6 65 theme whole 946:950 arg1 WES 970:972 WES 970:972 WES 970:972 Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). 37152991 6 65 theme whole 946:950 arg1 sequencing 958:967 whole exome sequencing 946:967 whole exome sequencing (WES) 946:973 Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). 37152991 8 66 theme first 1441:1445 arg1 domain 1447:1452 the first domain 1437:1452 the first domain 1437:1452 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 10 67 from phenotypes 1718:1727 arg1 patients 1732:1739 patients 1732:1739 patients with different DPM2 variants 1732:1768 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 8 68 theme severe 1463:1468 arg1 symptoms 1479:1486 more severe clinical symptoms 1458:1486 more severe clinical symptoms 1458:1486 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 0 69 theme mild 97:100 arg1 impairment 115:124 mild intellectual impairment 97:124 mild intellectual impairment 97:124 Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment. 37152991 8 70 theme reported 1286:1293 arg1 patients 1295:1302 the 4 previously reported patients 1269:1302 the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene 1269:1369 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 3 71 with siblings 563:570 arg1 form 584:587 a mild form 577:587 a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase 577:702 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 10 72 theme functional 1806:1815 arg1 studies 1817:1823 further functional studies 1798:1823 further functional studies 1798:1823 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 7 73 theme western 1087:1093 arg1 blot 1095:1098 western blot 1087:1098 western blot 1087:1098 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 1 74 theme lpid 277:280 arg1 glycosylation 282:294 lpid glycosylation 277:294 lpid glycosylation 277:294 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 3 75 theme developmental 606:618 arg1 delay 620:624 developmental delay 606:624 developmental delay 606:624 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 7 76 theme protein 1075:1081 arg1 level 1061:1065 the expression level 1046:1065 the expression level of DPM2 protein 1046:1081 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 7 77 gly hypoglycosylation 1168:1184 arg1 patients 1189:1196 patients 1189:1196 patients with CDG 1189:1205 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 7 78 theme abnormal 1219:1226 arg1 glycosylation 1237:1249 abnormal N-linked glycosylation 1219:1249 abnormal N-linked glycosylation 1219:1249 In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. 37152991 3 79 theme DPM2-CDG 592:599 arg1 form 584:587 a mild form 577:587 a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase 577:702 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 2 80 theme key 394:396 arg1 enzyme 398:403 a key enzyme 392:403 a key enzyme in glycosylation 392:420 DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported. 37152991 2 80 theme key 394:396 arg1 synthase 375:382 dolichol-phosphatemannose synthase 349:382 dolichol-phosphatemannose synthase (DPMS) 349:389 DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported. 37152991 3 81 theme intellectual 632:643 arg1 disability 645:654 mild intellectual disability 627:654 mild intellectual disability 627:654 Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. 37152991 2 82 theme heterotrimeric 322:335 arg1 complex 337:343 a heterotrimeric complex 320:343 a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation 320:420 DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported. 37152991 9 83 theme actual 1552:1557 arg1 relationship 1578:1589 the actual genotype-phenotype relationship 1548:1589 the actual genotype-phenotype relationship 1548:1589 However, the actual genotype-phenotype relationship needs more study. 37152991 10 84 theme studies 1817:1823 arg1 need 1790:1793 the need 1786:1793 the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity 1786:1900 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 8 85 theme gene 1366:1369 arg1 variants 1349:1356 homozygous or compound heterozygous variants 1313:1356 homozygous or compound heterozygous variants of DMP2 gene 1313:1369 We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. 37152991 4 86 used used 727:730 arg2 sequencing 712:721 Sanger sequencing 705:721 Sanger sequencing 705:721 Sanger sequencing was used to validate the variants identified in the siblings and their parents. 37152991 1 87 theme heterogeneous 204:216 arg1 group 218:222 a genetically heterogeneous group 190:222 a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation 190:294 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 87 theme heterogeneous 204:216 arg1 disorders 237:245 metabolic disorders 227:245 metabolic disorders caused by abnormal protein or lpid glycosylation 227:294 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 87 theme heterogeneous 204:216 arg1 disorders 152:160 Congenital disorders 141:160 Congenital disorders of glycosylation (CDGs) 141:184 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 87 theme heterogeneous 204:216 arg1 Introduction 127:138 Introduction 127:138 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 127:295 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 6 88 from mutation 866:873 arg1 exon 901:904 exon 4 901:906 exon 4 of DPM2 (NM_003863) 901:926 Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). 37152991 5 89 dep In 803:804 arg1 vitro 806:810 vitro 806:810 vitro 806:810 In vitro functional study was performed. 37152991 10 90 theme DPM2 1673:1676 arg1 gene 1678:1681 DPM2 gene 1673:1681 DPM2 gene 1673:1681 Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity. 37152991 1 91 theme disorders 237:245 arg1 group 218:222 a genetically heterogeneous group 190:222 a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation 190:294 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 91 theme disorders 237:245 arg1 disorders 237:245 metabolic disorders 227:245 metabolic disorders caused by abnormal protein or lpid glycosylation 227:294 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 91 theme disorders 237:245 arg1 disorders 152:160 Congenital disorders 141:160 Congenital disorders of glycosylation (CDGs) 141:184 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37152991 1 91 theme disorders 237:245 arg1 Introduction 127:138 Introduction 127:138 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 127:295 Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. 37066156 4 0 theme immune 894:899 arg1 responses 901:909 minimal immune responses 886:909 minimal immune responses 886:909 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 6 1 theme 4°C 1305:1307 arg1 storage 1309:1315 4°C storage 1305:1315 4°C storage 1305:1315 Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. 37066156 8 2 theme key 1725:1727 arg1 profiles 1872:1879 mouse immunogenicity profiles 1851:1879 mouse immunogenicity profiles 1851:1879 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 2 theme key 1725:1727 arg1 binding 1822:1828 binding 1822:1828 binding to ACE2 receptor 1822:1845 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 2 theme key 1725:1727 arg1 integrity 1785:1793 structural integrity 1774:1793 structural integrity 1774:1793 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 2 theme key 1725:1727 arg1 attributes 1737:1746 their key quality attributes 1719:1746 their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles 1719:1879 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 2 theme key 1725:1727 arg1 stability 1811:1819 conformational stability 1796:1819 conformational stability 1796:1819 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 2 theme key 1725:1727 arg1 size 1768:1771 molecular size 1758:1771 molecular size 1758:1771 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 5 3 theme ACE2 1228:1231 arg1 binding 1242:1248 ACE2 receptor binding 1228:1248 ACE2 receptor binding of AH-bound antigen 1228:1268 These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. 37066156 7 4 theme DCFHP 1493:1497 arg1 antigen 1499:1505 DCFHP antigen 1493:1505 DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles 1493:1620 Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. 37066156 4 5 theme Unadjuvanted 858:869 arg1 DCFHP 871:875 Unadjuvanted DCFHP 858:875 Unadjuvanted DCFHP 858:875 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 8 6 theme molecular 1758:1766 arg1 size 1768:1771 molecular size 1758:1771 molecular size 1758:1771 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 1 7 theme safe 197:200 arg1 vaccines 243:250 safe and effective second-generation COVID-19 vaccines 197:250 safe and effective second-generation COVID-19 vaccines 197:250 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. 37066156 9 8 theme DCFHP 1984:1988 arg1 candidate 1998:2006 an AH-adjuvanted DCFHP vaccine candidate 1967:2006 an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells 1967:2028 Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells. 37066156 3 9 dep in 829:830 arg1 vitro 832:836 vitro 832:836 vitro 832:836 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 1 10 theme effective 206:214 arg1 vaccines 243:250 safe and effective second-generation COVID-19 vaccines 197:250 safe and effective second-generation COVID-19 vaccines 197:250 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. 37066156 4 11 theme pseudovirus 970:980 arg1 titers 997:1002 greatly enhanced pseudovirus neutralization titers 953:1002 greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH 953:1073 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 9 12 theme candidate 1998:2006 arg1 development 1952:1962 future preclinical and clinical development 1920:1962 future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells 1920:2028 Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells. 37066156 6 13 theme concomitant 1355:1365 arg1 decreases 1367:1375 concomitant decreases 1355:1375 concomitant decreases in the ability to desorb the antigen from the AH 1355:1424 Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. 37066156 1 14 theme COVID-19 234:241 arg1 vaccines 243:250 safe and effective second-generation COVID-19 vaccines 197:250 safe and effective second-generation COVID-19 vaccines 197:250 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. 37066156 0 15 theme different 156:164 arg1 lines 171:175 two different cell lines 152:175 two different cell lines 152:175 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 3 16 theme Varying 640:646 arg1 levels 648:653 Varying levels 640:653 Varying levels of phosphate buffer 640:673 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 8 17 theme conformational 1796:1809 arg1 stability 1811:1819 conformational stability 1796:1819 conformational stability 1796:1819 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 6 18 from AH 1423:1424 arg1 antigen 1406:1412 the antigen 1402:1412 the antigen from the AH 1402:1424 Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. 37066156 3 19 theme buffer 668:673 arg1 levels 648:653 Varying levels 640:653 Varying levels of phosphate buffer 640:673 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 0 20 theme adjuvanted 72:81 arg1 antigen 130:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 5 21 theme stability 1132:1140 arg1 properties 1142:1151 their in vitro stability properties 1117:1151 their in vitro stability properties 1117:1151 These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. 37066156 7 22 theme oligosaccharide 1597:1611 arg1 profiles 1613:1620 their N-linked oligosaccharide profiles 1582:1620 their N-linked oligosaccharide profiles 1582:1620 Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. 37066156 3 23 theme stability 838:846 arg1 profiles 848:855 in vitro stability profiles 829:855 (2) in vitro stability profiles 825:855 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 0 24 theme Spike 94:98 arg1 antigen 130:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 8 25 theme mouse 1851:1855 arg1 profiles 1872:1879 mouse immunogenicity profiles 1851:1879 mouse immunogenicity profiles 1851:1879 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 3 26 theme in 829:830 arg1 profiles 848:855 in vitro stability profiles 829:855 (2) in vitro stability profiles 825:855 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 0 27 theme nanoparticle 109:120 arg1 antigen 130:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 2 28 theme cell 565:568 arg1 lines 570:574 two different cell lines 551:574 two different cell lines 551:574 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 5 29 theme in 1123:1124 arg1 properties 1142:1151 their in vitro stability properties 1117:1151 their in vitro stability properties 1117:1151 These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. 37066156 4 30 theme antigen 1052:1058 arg1 antigen 1052:1058 the DCFHP antigen 1042:1058 the DCFHP antigen adsorbed to AH 1042:1073 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 4 30 theme antigen 1052:1058 arg1 % 1023:1023 ∼100% 1019:1023 ∼100% 1019:1023 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 4 30 theme antigen 1052:1058 arg1 % 1029:1029 ∼40% 1026:1029 ∼40% 1026:1029 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 4 30 theme antigen 1052:1058 arg1 % 1037:1037 ∼10% 1034:1037 ∼10% 1034:1037 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 0 31 theme Formulation 0:10 arg1 development 12:22 Formulation development and comparability studies 0:48 development 12:22 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 1 32 theme high 322:325 arg1 priority 327:334 a high priority 320:334 a high priority to expand global coverage 320:360 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. 37066156 2 33 theme vaccine 502:508 arg1 antigen 510:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen 446:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP) 446:531 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 33 theme vaccine 502:508 arg1 DCFHP 526:530 called DCFHP 519:530 called DCFHP 519:530 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 34 theme ferritin 480:487 arg1 antigen 510:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen 446:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP) 446:531 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 34 theme ferritin 480:487 arg1 DCFHP 526:530 called DCFHP 519:530 called DCFHP 519:530 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 6 35 from decreases 1367:1375 arg1 ability 1384:1390 the ability to desorb the antigen from the AH 1380:1424 the ability to desorb the antigen from the AH 1380:1424 Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. 37066156 7 36 from differences 1567:1577 arg1 profiles 1613:1620 their N-linked oligosaccharide profiles 1582:1620 their N-linked oligosaccharide profiles 1582:1620 Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. 37066156 4 37 theme % 1037:1037 arg1 independent 1004:1014 independent 1004:1014 independent 1004:1014 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 8 38 theme quality 1729:1735 arg1 profiles 1872:1879 mouse immunogenicity profiles 1851:1879 mouse immunogenicity profiles 1851:1879 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 38 theme quality 1729:1735 arg1 binding 1822:1828 binding 1822:1828 binding to ACE2 receptor 1822:1845 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 38 theme quality 1729:1735 arg1 integrity 1785:1793 structural integrity 1774:1793 structural integrity 1774:1793 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 38 theme quality 1729:1735 arg1 attributes 1737:1746 their key quality attributes 1719:1746 their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles 1719:1879 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 38 theme quality 1729:1735 arg1 stability 1811:1819 conformational stability 1796:1819 conformational stability 1796:1819 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 38 theme quality 1729:1735 arg1 size 1768:1771 molecular size 1758:1771 molecular size 1758:1771 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 2 39 theme SARS-CoV-2 463:472 arg1 antigen 510:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen 446:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP) 446:531 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 39 theme SARS-CoV-2 463:472 arg1 DCFHP 526:530 called DCFHP 519:530 called DCFHP 519:530 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 1 40 theme global 346:351 arg1 coverage 353:360 global coverage 346:360 global coverage 346:360 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. 37066156 8 41 from attributes 1737:1746 arg1 similar 1708:1714 similar 1708:1714 similar 1708:1714 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 3 42 theme interactions 727:738 arg1 extent 687:692 extent 687:692 extent 687:692 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 3 42 theme interactions 727:738 arg1 strength 698:705 strength 698:705 strength 698:705 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 8 43 gly glycoforms 1661:1670 arg1 DCFHP 1655:1659 different DCFHP glycoforms 1645:1670 different DCFHP glycoforms 1645:1670 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 3 44 dep extent 687:692 arg1 the 683:685 the 683:685 the 683:685 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 2 45 with studies 433:439 arg1 antigen 510:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen 446:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP) 446:531 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 45 with studies 433:439 arg1 DCFHP 526:530 called DCFHP 519:530 called DCFHP 519:530 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 9 46 theme preclinical 1927:1937 arg1 development 1952:1962 future preclinical and clinical development 1920:1962 future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells 1920:2028 Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells. 37066156 6 47 theme storage 1309:1315 arg1 month 1296:1300 one month 1292:1300 one month of 4°C storage 1292:1315 Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. 37066156 0 48 with studies 42:48 arg1 antigen 130:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 2 49 theme formulation 391:401 arg1 development 403:413 formulation development and comparability studies 391:439 development 403:413 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 1 50 theme stability 289:297 arg1 requirements 299:310 affordability and storage stability requirements 263:310 affordability and storage stability requirements 263:310 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. 37066156 4 51 theme minimal 886:892 arg1 responses 901:909 minimal immune responses 886:909 minimal immune responses 886:909 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 9 52 theme clinical 1943:1950 arg1 development 1952:1962 future preclinical and clinical development 1920:1962 future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells 1920:2028 Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells. 37066156 8 53 theme DCFHP 1655:1659 arg1 glycoforms 1661:1670 different DCFHP glycoforms 1645:1670 different DCFHP glycoforms 1645:1670 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 5 54 theme receptor 1233:1240 arg1 binding 1242:1248 ACE2 receptor binding 1228:1248 ACE2 receptor binding of AH-bound antigen 1228:1268 These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. 37066156 7 55 theme comparability 1465:1477 arg1 assessment 1479:1488 a comparability assessment 1463:1488 a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles 1463:1620 Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. 37066156 6 56 with antigenicity 1337:1348 arg1 decreases 1367:1375 concomitant decreases 1355:1375 concomitant decreases in the ability to desorb the antigen from the AH 1355:1424 Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. 37066156 9 57 theme AH-adjuvanted 1970:1982 arg1 candidate 1998:2006 an AH-adjuvanted DCFHP vaccine candidate 1967:2006 an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells 1967:2028 Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells. 37066156 9 58 theme vaccine 1990:1996 arg1 candidate 1998:2006 an AH-adjuvanted DCFHP vaccine candidate 1967:2006 an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells 1967:2028 Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells. 37066156 3 59 theme in 793:794 arg1 performance 801:811 in vivo performance 793:811 (1) in vivo performance in mice 789:819 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 1 60 theme second-generation 216:232 arg1 vaccines 243:250 safe and effective second-generation COVID-19 vaccines 197:250 safe and effective second-generation COVID-19 vaccines 197:250 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. 37066156 4 61 theme enhanced 961:968 arg1 titers 997:1002 greatly enhanced pseudovirus neutralization titers 953:1002 greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH 953:1073 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 0 62 theme cell 166:169 arg1 lines 171:175 two different cell lines 152:175 two different cell lines 152:175 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 8 63 theme structural 1774:1783 arg1 integrity 1785:1793 structural integrity 1774:1793 structural integrity 1774:1793 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 1 64 theme vaccines 243:250 arg1 development 182:192 The development 178:192 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements 178:310 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. 37066156 4 65 theme neutralization 982:995 arg1 titers 997:1002 greatly enhanced pseudovirus neutralization titers 953:1002 greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH 953:1073 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 9 66 theme CHO 2020:2022 arg1 cells 2024:2028 CHO cells 2020:2028 CHO cells 2020:2028 Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells. 37066156 4 67 theme AH-adjuvanted 917:929 arg1 formulations 931:942 AH-adjuvanted formulations 917:942 AH-adjuvanted formulations 917:942 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 6 68 theme small 1318:1322 arg1 increases 1324:1332 small increases 1318:1332 small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH 1318:1424 Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. 37066156 3 69 theme phosphate 658:666 arg1 buffer 668:673 phosphate buffer 658:673 phosphate buffer 658:673 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 0 70 theme SARS-CoV-2 83:92 arg1 antigen 130:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 3 71 dep profiles 848:855 arg1 2 826:826 2 826:826 2 826:826 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 7 72 theme N-linked 1588:1595 arg1 profiles 1613:1620 their N-linked oligosaccharide profiles 1582:1620 their N-linked oligosaccharide profiles 1582:1620 Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. 37066156 0 73 theme ferritin 100:107 arg1 antigen 130:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 8 74 theme ACE2 1833:1836 arg1 receptor 1838:1845 ACE2 receptor 1833:1845 ACE2 receptor 1833:1845 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 4 75 theme % 1029:1029 arg1 independent 1004:1014 independent 1004:1014 independent 1004:1014 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 3 76 from performance 801:811 arg1 mice 816:819 mice 816:819 mice 816:819 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 0 77 theme vaccine 122:128 arg1 antigen 130:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 3 78 dep in 793:794 arg1 vivo 796:799 vivo 796:799 vivo 796:799 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 7 79 theme expected 1558:1565 arg1 differences 1567:1577 expected differences 1558:1577 expected differences in their N-linked oligosaccharide profiles 1558:1620 Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. 37066156 4 80 theme independent 1004:1014 arg1 titers 997:1002 greatly enhanced pseudovirus neutralization titers 953:1002 greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH 953:1073 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 2 81 dep describe 382:389 arg1 AH 635:636 AH 635:636 AH 635:636 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 81 dep describe 382:389 arg1 Alhydrogel 623:632 Alhydrogel 623:632 Alhydrogel 623:632 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 3 82 dep performance 801:811 arg1 1 790:790 1 790:790 1 790:790 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 8 83 theme immunogenicity 1857:1870 arg1 profiles 1872:1879 mouse immunogenicity profiles 1851:1879 mouse immunogenicity profiles 1851:1879 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 2 84 theme different 555:563 arg1 lines 570:574 two different cell lines 551:574 two different cell lines 551:574 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 7 85 link N-linked 1588:1595 arg1 profiles 1613:1620 their N-linked oligosaccharide profiles 1582:1620 their N-linked oligosaccharide profiles 1582:1620 Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. 37066156 1 86 theme affordability 263:275 arg1 requirements 299:310 affordability and storage stability requirements 263:310 affordability and storage stability requirements 263:310 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. 37066156 4 87 theme % 1023:1023 arg1 independent 1004:1014 independent 1004:1014 independent 1004:1014 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 4 88 theme DCFHP 1046:1050 arg1 antigen 1052:1058 the DCFHP antigen 1042:1058 the DCFHP antigen adsorbed to AH 1042:1073 Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. 37066156 2 89 with development 403:413 arg1 antigen 510:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen 446:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP) 446:531 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 89 with development 403:413 arg1 DCFHP 526:530 called DCFHP 519:530 called DCFHP 519:530 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 90 theme comparability 419:431 arg1 studies 433:439 formulation development and comparability studies 391:439 studies 433:439 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 0 91 theme comparability 28:40 arg1 studies 42:48 Formulation development and comparability studies 0:48 studies 42:48 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 5 92 theme competitive 1196:1206 arg1 ELISA 1208:1212 a competitive ELISA 1194:1212 a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen 1194:1268 These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. 37066156 2 93 theme nanoparticle 489:500 arg1 antigen 510:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen 446:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP) 446:531 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 93 theme nanoparticle 489:500 arg1 DCFHP 526:530 called DCFHP 519:530 called DCFHP 519:530 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 8 94 from similar 1708:1714 arg1 profiles 1872:1879 mouse immunogenicity profiles 1851:1879 mouse immunogenicity profiles 1851:1879 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 94 from similar 1708:1714 arg1 binding 1822:1828 binding 1822:1828 binding to ACE2 receptor 1822:1845 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 94 from similar 1708:1714 arg1 integrity 1785:1793 structural integrity 1774:1793 structural integrity 1774:1793 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 94 from similar 1708:1714 arg1 attributes 1737:1746 their key quality attributes 1719:1746 their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles 1719:1879 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 94 from similar 1708:1714 arg1 stability 1811:1819 conformational stability 1796:1819 conformational stability 1796:1819 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 8 94 from similar 1708:1714 arg1 size 1768:1771 molecular size 1758:1771 molecular size 1758:1771 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 2 95 theme spike 474:478 arg1 antigen 510:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen 446:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP) 446:531 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 95 theme spike 474:478 arg1 DCFHP 526:530 called DCFHP 519:530 called DCFHP 519:530 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 5 96 dep in 1123:1124 arg1 vitro 1126:1130 vitro 1126:1130 vitro 1126:1130 These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. 37066156 3 97 from profiles 848:855 arg1 mice 816:819 mice 816:819 mice 816:819 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 5 98 theme antigen 1262:1268 arg1 binding 1242:1248 ACE2 receptor binding 1228:1248 ACE2 receptor binding of AH-bound antigen 1228:1268 These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. 37066156 2 99 theme self-assembled 448:461 arg1 antigen 510:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen 446:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP) 446:531 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 99 theme self-assembled 448:461 arg1 DCFHP 526:530 called DCFHP 519:530 called DCFHP 519:530 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 0 100 theme aluminum-salt 58:70 arg1 antigen 130:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 5 101 theme biophysical 1170:1180 arg1 studies 1182:1188 biophysical studies 1170:1188 biophysical studies 1170:1188 These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. 37066156 2 102 theme called 519:524 arg1 antigen 510:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen 446:516 a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP) 446:531 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 2 102 theme called 519:524 arg1 DCFHP 526:530 called DCFHP 519:530 called DCFHP 519:530 In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). 37066156 7 103 theme antigen 1499:1505 arg1 assessment 1479:1488 a comparability assessment 1463:1488 a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles 1463:1620 Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. 37066156 3 104 theme antigen-adjuvant 710:725 arg1 interactions 727:738 antigen-adjuvant interactions 710:738 antigen-adjuvant interactions 710:738 Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. 37066156 0 105 with development 12:22 arg1 antigen 130:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen 55:136 Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines. 37066156 6 106 from increases 1324:1332 arg1 antigenicity 1337:1348 antigenicity 1337:1348 antigenicity with concomitant decreases in the ability to desorb the antigen from the AH 1337:1424 Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. 37066156 7 107 theme CHO 1531:1533 arg1 cells 1535:1539 Expi293 and CHO cells 1519:1539 cells 1535:1539 Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. 37066156 5 108 theme AH-bound 1253:1260 arg1 antigen 1262:1268 AH-bound antigen 1253:1268 AH-bound antigen 1253:1268 These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. 37066156 7 109 theme Expi293 1519:1525 arg1 cells 1535:1539 Expi293 and CHO cells 1519:1539 cells 1535:1539 Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. 37066156 9 110 theme future 1920:1925 arg1 development 1952:1962 future preclinical and clinical development 1920:1962 future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells 1920:2028 Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells. 37066156 8 111 theme different 1645:1653 arg1 glycoforms 1661:1670 different DCFHP glycoforms 1645:1670 different DCFHP glycoforms 1645:1670 Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. 37066156 1 112 theme storage 281:287 arg1 stability 289:297 storage stability 281:297 storage stability 281:297 The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. 36642382 1 0 theme main 141:144 arg1 enzyme 178:183 its main receptor angiotensin-converting enzyme 2 137:185 its main receptor angiotensin-converting enzyme 2 (ACE2) 137:192 SARS-CoV-2 enters human cells through its main receptor angiotensin-converting enzyme 2 (ACE2), which constitutes a limiting factor of an infection. 36642382 1 0 theme main 141:144 arg1 ACE2 188:191 ACE2 188:191 ACE2 188:191 SARS-CoV-2 enters human cells through its main receptor angiotensin-converting enzyme 2 (ACE2), which constitutes a limiting factor of an infection. 36642382 8 1 theme related 1174:1180 arg1 molecules 1187:1195 other SARS-CoV-2 related host molecules 1157:1195 other SARS-CoV-2 related host molecules 1157:1195 In addition, by screening other SARS-CoV-2 related host molecules, we found that IL-13 and RV significantly regulated mRNA, but not protein of TMPRSS2 and NRP1. 36642382 5 2 theme glycosylation 883:895 arg1 process 897:903 N-linked glycosylation process 874:903 N-linked glycosylation process 874:903 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 1 3 theme receptor 146:153 arg1 enzyme 178:183 its main receptor angiotensin-converting enzyme 2 137:185 its main receptor angiotensin-converting enzyme 2 (ACE2) 137:192 SARS-CoV-2 enters human cells through its main receptor angiotensin-converting enzyme 2 (ACE2), which constitutes a limiting factor of an infection. 36642382 1 3 theme receptor 146:153 arg1 ACE2 188:191 ACE2 188:191 ACE2 188:191 SARS-CoV-2 enters human cells through its main receptor angiotensin-converting enzyme 2 (ACE2), which constitutes a limiting factor of an infection. 36642382 6 4 theme House 970:974 arg1 allergen 986:993 House dust mite allergen 970:993 House dust mite allergen 970:993 House dust mite allergen did not affect the expression of ACE2. 36642382 4 5 theme isoforms 557:564 arg1 expression 521:530 expression 521:530 expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium 521:657 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 0 6 theme airway 80:85 arg1 epithelium 87:96 human airway epithelium 74:96 human airway epithelium 74:96 Regulation of ACE2 isoforms by type 2 inflammation and viral infection in human airway epithelium. 36642382 5 7 from availability 919:930 arg1 side 946:949 the apical side 935:949 the apical side of ciliated cells 935:967 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 2 8 theme novel 278:282 arg1 isoforms 289:296 novel ACE2 isoforms 278:296 novel ACE2 isoforms 278:296 Recent findings demonstrating novel ACE2 isoforms implicate that this receptor is regulated in a more complex way than previously anticipated. 36642382 5 9 theme full 831:834 arg1 protein 848:854 full length ACE2 protein 831:854 full length ACE2 protein 831:854 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 1 10 theme infection 237:245 arg1 factor 224:229 a limiting factor 213:229 a limiting factor of an infection 213:245 SARS-CoV-2 enters human cells through its main receptor angiotensin-converting enzyme 2 (ACE2), which constitutes a limiting factor of an infection. 36642382 0 11 theme human 74:78 arg1 epithelium 87:96 human airway epithelium 74:96 human airway epithelium 74:96 Regulation of ACE2 isoforms by type 2 inflammation and viral infection in human airway epithelium. 36642382 0 12 from inflammation 38:49 arg1 epithelium 87:96 human airway epithelium 74:96 human airway epithelium 74:96 Regulation of ACE2 isoforms by type 2 inflammation and viral infection in human airway epithelium. 36642382 5 13 theme ciliated 954:961 arg1 cells 963:967 ciliated cells 954:967 ciliated cells 954:967 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 3 14 theme variants 493:500 arg1 abundance 469:477 the abundance 465:477 the abundance of these ACE2 variants 465:500 However, it remains unknown how various inflammatory conditions influence the abundance of these ACE2 variants. 36642382 4 15 theme human 635:639 arg1 epithelium 648:657 primary human airway epithelium 627:657 primary human airway epithelium 627:657 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 4 16 theme viral 690:694 arg1 infection 696:704 viral infection 690:704 viral infection 690:704 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 5 17 theme cells 963:967 arg1 side 946:949 the apical side 935:949 the apical side of ciliated cells 935:967 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 1 18 theme angiotensin-converting 155:176 arg1 enzyme 178:183 its main receptor angiotensin-converting enzyme 2 137:185 its main receptor angiotensin-converting enzyme 2 (ACE2) 137:192 SARS-CoV-2 enters human cells through its main receptor angiotensin-converting enzyme 2 (ACE2), which constitutes a limiting factor of an infection. 36642382 1 18 theme angiotensin-converting 155:176 arg1 ACE2 188:191 ACE2 188:191 ACE2 188:191 SARS-CoV-2 enters human cells through its main receptor angiotensin-converting enzyme 2 (ACE2), which constitutes a limiting factor of an infection. 36642382 5 19 theme main 741:744 arg1 interleukin-13 721:734 interleukin-13 721:734 interleukin-13 721:734 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 5 19 theme main 741:744 arg1 cytokine 753:760 the main type 2 cytokine 737:760 the main type 2 cytokine 737:760 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 5 20 theme process 897:903 arg1 alteration 860:869 alteration 860:869 alteration of N-linked glycosylation process 860:903 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 5 21 gly glycosylation 814:826 arg1 protein 848:854 full length ACE2 protein 831:854 full length ACE2 protein 831:854 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 9 22 from milieu 1464:1469 arg1 airways 1478:1484 the airways 1474:1484 the airways 1474:1484 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 2 23 theme Recent 248:253 arg1 findings 255:262 Recent findings 248:262 Recent findings demonstrating novel ACE2 isoforms 248:296 Recent findings demonstrating novel ACE2 isoforms implicate that this receptor is regulated in a more complex way than previously anticipated. 36642382 3 24 theme various 423:429 arg1 conditions 444:453 various inflammatory conditions 423:453 various inflammatory conditions 423:453 However, it remains unknown how various inflammatory conditions influence the abundance of these ACE2 variants. 36642382 5 25 theme ACE2 792:795 arg1 mRNA 797:800 long ACE2 mRNA 787:800 long ACE2 mRNA 787:800 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 7 26 theme ACE2 1071:1074 arg1 mRNA 1076:1079 short ACE2 mRNA 1065:1079 short ACE2 mRNA 1065:1079 Rhinovirus infection increased short ACE2 mRNA, but it did not influence its protein expression. 36642382 5 27 theme type 746:749 arg1 interleukin-13 721:734 interleukin-13 721:734 interleukin-13 721:734 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 5 27 theme type 746:749 arg1 cytokine 753:760 the main type 2 cytokine 737:760 the main type 2 cytokine 737:760 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 4 28 theme allergic 664:671 arg1 inflammation 673:684 allergic inflammation 664:684 allergic inflammation 664:684 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 5 29 theme mRNA 797:800 arg1 expression 773:782 expression 773:782 expression of long ACE2 mRNA 773:800 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 4 30 theme mRNA 540:543 arg1 isoforms 557:564 ACE2 mRNA and protein isoforms 535:564 ACE2 mRNA and protein isoforms 535:564 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 5 31 theme ACE2 843:846 arg1 protein 848:854 full length ACE2 protein 831:854 full length ACE2 protein 831:854 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 5 32 theme protein 848:854 arg1 glycosylation 814:826 glycosylation 814:826 glycosylation of full length ACE2 protein 814:854 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 9 33 theme intrinsic 1407:1415 arg1 differences 1417:1427 intrinsic differences 1407:1427 intrinsic differences 1407:1427 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 0 34 theme isoforms 19:26 arg1 Regulation 0:9 Regulation 0:9 Regulation of ACE2 isoforms by type 2 inflammation and viral infection in human airway epithelium. 0:97 Regulation of ACE2 isoforms by type 2 inflammation and viral infection in human airway epithelium. 36642382 4 35 theme ACE2 535:538 arg1 mRNA 540:543 ACE2 mRNA 535:543 ACE2 mRNA 535:543 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 9 36 from epithelium 1375:1384 arg1 comparable 1339:1348 comparable 1339:1348 comparable 1339:1348 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 5 37 theme apical 939:944 arg1 side 946:949 the apical side 935:949 the apical side of ciliated cells 935:967 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 9 38 theme proteins 1326:1333 arg1 Regulation 1292:1301 Regulation 1292:1301 Regulation of ACE2 and other host proteins 1292:1333 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 9 39 theme differences 1417:1427 arg1 lack 1399:1402 lack 1399:1402 lack of intrinsic differences 1399:1427 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 0 40 theme ACE2 14:17 arg1 isoforms 19:26 ACE2 isoforms 14:26 ACE2 isoforms 14:26 Regulation of ACE2 isoforms by type 2 inflammation and viral infection in human airway epithelium. 36642382 4 41 theme protein 549:555 arg1 isoforms 557:564 ACE2 mRNA and protein isoforms 535:564 ACE2 mRNA and protein isoforms 535:564 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 7 42 theme short 1065:1069 arg1 mRNA 1076:1079 short ACE2 mRNA 1065:1079 short ACE2 mRNA 1065:1079 Rhinovirus infection increased short ACE2 mRNA, but it did not influence its protein expression. 36642382 2 43 theme ACE2 284:287 arg1 isoforms 289:296 novel ACE2 isoforms 278:296 novel ACE2 isoforms 278:296 Recent findings demonstrating novel ACE2 isoforms implicate that this receptor is regulated in a more complex way than previously anticipated. 36642382 6 44 theme ACE2 1028:1031 arg1 expression 1014:1023 the expression 1010:1023 the expression of ACE2 1010:1031 House dust mite allergen did not affect the expression of ACE2. 36642382 0 45 theme type 31:34 arg1 inflammation 38:49 type 2 inflammation 31:49 type 2 inflammation 31:49 Regulation of ACE2 isoforms by type 2 inflammation and viral infection in human airway epithelium. 36642382 9 46 theme ACE2 1306:1309 arg1 Regulation 1292:1301 Regulation 1292:1301 Regulation of ACE2 and other host proteins 1292:1333 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 7 47 theme Rhinovirus 1034:1043 arg1 infection 1045:1053 Rhinovirus infection 1034:1053 Rhinovirus infection 1034:1053 Rhinovirus infection increased short ACE2 mRNA, but it did not influence its protein expression. 36642382 0 48 from infection 61:69 arg1 epithelium 87:96 human airway epithelium 74:96 human airway epithelium 74:96 Regulation of ACE2 isoforms by type 2 inflammation and viral infection in human airway epithelium. 36642382 8 49 theme TMPRSS2 1274:1280 arg1 protein 1263:1269 protein 1263:1269 protein of TMPRSS2 and NRP1 1263:1289 In addition, by screening other SARS-CoV-2 related host molecules, we found that IL-13 and RV significantly regulated mRNA, but not protein of TMPRSS2 and NRP1. 36642382 3 50 theme inflammatory 431:442 arg1 conditions 444:453 various inflammatory conditions 423:453 various inflammatory conditions 423:453 However, it remains unknown how various inflammatory conditions influence the abundance of these ACE2 variants. 36642382 4 51 from expression 521:530 arg1 epithelium 648:657 primary human airway epithelium 627:657 primary human airway epithelium 627:657 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 5 52 link N-linked 874:881 arg1 process 897:903 N-linked glycosylation process 874:903 N-linked glycosylation process 874:903 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 6 53 theme mite 981:984 arg1 allergen 986:993 House dust mite allergen 970:993 House dust mite allergen 970:993 House dust mite allergen did not affect the expression of ACE2. 36642382 4 54 theme spatial 603:609 arg1 localization 611:622 spatial localization 603:622 spatial localization 603:622 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 9 55 from dependence 1433:1442 arg1 milieu 1464:1469 the inflammatory milieu 1447:1469 the inflammatory milieu in the airways 1447:1484 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 4 56 theme primary 627:633 arg1 epithelium 648:657 primary human airway epithelium 627:657 primary human airway epithelium 627:657 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 9 57 theme other 1315:1319 arg1 proteins 1326:1333 other host proteins 1315:1333 other host proteins 1315:1333 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 8 58 theme host 1182:1185 arg1 molecules 1187:1195 other SARS-CoV-2 related host molecules 1157:1195 other SARS-CoV-2 related host molecules 1157:1195 In addition, by screening other SARS-CoV-2 related host molecules, we found that IL-13 and RV significantly regulated mRNA, but not protein of TMPRSS2 and NRP1. 36642382 9 59 theme inflammatory 1451:1462 arg1 milieu 1464:1469 the inflammatory milieu 1447:1469 the inflammatory milieu in the airways 1447:1484 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 5 60 theme long 787:790 arg1 mRNA 797:800 long ACE2 mRNA 787:800 long ACE2 mRNA 787:800 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 9 61 theme host 1321:1324 arg1 proteins 1326:1333 other host proteins 1315:1333 other host proteins 1315:1333 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 3 62 theme ACE2 488:491 arg1 variants 493:500 these ACE2 variants 482:500 these ACE2 variants 482:500 However, it remains unknown how various inflammatory conditions influence the abundance of these ACE2 variants. 36642382 8 63 theme other 1157:1161 arg1 molecules 1187:1195 other SARS-CoV-2 related host molecules 1157:1195 other SARS-CoV-2 related host molecules 1157:1195 In addition, by screening other SARS-CoV-2 related host molecules, we found that IL-13 and RV significantly regulated mRNA, but not protein of TMPRSS2 and NRP1. 36642382 7 64 theme protein 1111:1117 arg1 expression 1119:1128 its protein expression 1107:1128 its protein expression 1107:1128 Rhinovirus infection increased short ACE2 mRNA, but it did not influence its protein expression. 36642382 1 65 theme human 117:121 arg1 cells 123:127 human cells 117:127 human cells 117:127 SARS-CoV-2 enters human cells through its main receptor angiotensin-converting enzyme 2 (ACE2), which constitutes a limiting factor of an infection. 36642382 9 66 from comparable 1339:1348 arg1 epithelium 1375:1384 healthy and asthmatic epithelium 1353:1384 healthy and asthmatic epithelium 1353:1384 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 9 67 theme asthmatic 1365:1373 arg1 epithelium 1375:1384 healthy and asthmatic epithelium 1353:1384 healthy and asthmatic epithelium 1353:1384 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 36642382 2 68 dep way 358:360 arg1 anticipated 378:388 anticipated 378:388 anticipated 378:388 Recent findings demonstrating novel ACE2 isoforms implicate that this receptor is regulated in a more complex way than previously anticipated. 36642382 8 69 theme NRP1 1286:1289 arg1 protein 1263:1269 protein 1263:1269 protein of TMPRSS2 and NRP1 1263:1289 In addition, by screening other SARS-CoV-2 related host molecules, we found that IL-13 and RV significantly regulated mRNA, but not protein of TMPRSS2 and NRP1. 36642382 0 70 theme viral 55:59 arg1 infection 61:69 viral infection 55:69 viral infection 55:69 Regulation of ACE2 isoforms by type 2 inflammation and viral infection in human airway epithelium. 36642382 5 71 theme length 836:841 arg1 protein 848:854 full length ACE2 protein 831:854 full length ACE2 protein 831:854 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 2 72 theme complex 350:356 arg1 way 358:360 a more complex way 343:360 a more complex way than previously anticipated 343:388 Recent findings demonstrating novel ACE2 isoforms implicate that this receptor is regulated in a more complex way than previously anticipated. 36642382 4 73 theme airway 641:646 arg1 epithelium 648:657 primary human airway epithelium 627:657 primary human airway epithelium 627:657 Hence, we studied expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in primary human airway epithelium upon allergic inflammation and viral infection. 36642382 1 74 theme limiting 215:222 arg1 factor 224:229 a limiting factor 213:229 a limiting factor of an infection 213:245 SARS-CoV-2 enters human cells through its main receptor angiotensin-converting enzyme 2 (ACE2), which constitutes a limiting factor of an infection. 36642382 6 75 theme dust 976:979 arg1 allergen 986:993 House dust mite allergen 970:993 House dust mite allergen 970:993 House dust mite allergen did not affect the expression of ACE2. 36642382 8 76 theme SARS-CoV-2 1163:1172 arg1 molecules 1187:1195 other SARS-CoV-2 related host molecules 1157:1195 other SARS-CoV-2 related host molecules 1157:1195 In addition, by screening other SARS-CoV-2 related host molecules, we found that IL-13 and RV significantly regulated mRNA, but not protein of TMPRSS2 and NRP1. 36642382 5 77 theme N-linked 874:881 arg1 process 897:903 N-linked glycosylation process 874:903 N-linked glycosylation process 874:903 We found that interleukin-13, the main type 2 cytokine, decreased expression of long ACE2 mRNA and reduced glycosylation of full length ACE2 protein via alteration of N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. 36642382 9 78 theme healthy 1353:1359 arg1 epithelium 1375:1384 healthy and asthmatic epithelium 1353:1384 healthy and asthmatic epithelium 1353:1384 Regulation of ACE2 and other host proteins was comparable in healthy and asthmatic epithelium, underlining lack of intrinsic differences but dependence on the inflammatory milieu in the airways. 35460679 0 0 theme protein 88:94 arg1 expression 96:105 Angomonas deanei heat-shock protein expression 60:105 Angomonas deanei heat-shock protein expression 60:105 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 3 1 theme TM 713:714 arg1 effects 702:708 the effects 698:708 the effects of TM in the association between Angomonas deanei and its symbiotic bacterium 698:786 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 6 2 theme structures 1474:1483 arg1 biogenesis 1442:1451 biogenesis 1442:1451 biogenesis 1442:1451 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 6 2 theme structures 1474:1483 arg1 division 1457:1464 division 1457:1464 division 1457:1464 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 1 3 theme eukaryotic 261:270 arg1 cells 272:276 eukaryotic cells 261:276 eukaryotic cells 261:276 The endoplasmic reticulum (ER) presents unique properties to establishing bacterium symbiosis in eukaryotic cells since it synthesizes and glycosylates essential molecules like proteins and lipids. 35460679 0 4 theme heat-shock 77:86 arg1 expression 96:105 Angomonas deanei heat-shock protein expression 60:105 Angomonas deanei heat-shock protein expression 60:105 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 6 5 theme ER 1277:1278 arg1 importance 1259:1268 the importance 1255:1268 the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes 1255:1374 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 1 6 theme endoplasmic 168:178 arg1 ER 191:192 ER 191:192 ER 191:192 The endoplasmic reticulum (ER) presents unique properties to establishing bacterium symbiosis in eukaryotic cells since it synthesizes and glycosylates essential molecules like proteins and lipids. 35460679 1 6 theme endoplasmic 168:178 arg1 reticulum 180:188 The endoplasmic reticulum 164:188 The endoplasmic reticulum (ER) 164:193 The endoplasmic reticulum (ER) presents unique properties to establishing bacterium symbiosis in eukaryotic cells since it synthesizes and glycosylates essential molecules like proteins and lipids. 35460679 6 7 theme cell 1469:1472 arg1 structures 1474:1483 cell structures 1469:1483 cell structures 1469:1483 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 5 8 theme ER 1064:1065 arg1 stress 1067:1072 ER stress 1064:1072 ER stress in trypanosomatids 1064:1091 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 4 9 theme increased 957:965 arg1 distance 967:974 an increased distance 954:974 an increased distance between the symbiont and the ER 954:1006 Cells treated with the inhibitor showed a decrease in proliferation, enlargement of the ER and Golgi cisternae and an increased distance between the symbiont and the ER. 35460679 0 10 from Effect 0:5 arg1 association 118:128 the association 114:128 the association with the endosymbiotic bacterium 114:161 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 0 10 from Effect 0:5 arg1 expression 96:105 Angomonas deanei heat-shock protein expression 60:105 Angomonas deanei heat-shock protein expression 60:105 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 2 11 link N-linked 432:439 arg1 glycosylation 441:453 the N-linked glycosylation 428:453 the N-linked glycosylation in eukaryotes 428:467 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 5 12 theme Hsp90 1201:1205 arg1 chaperone 1207:1215 the Hsp90 chaperone 1197:1215 the Hsp90 chaperone 1197:1215 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 6 13 contain has 1409:1411 arg2 importance 1424:1433 recognized importance 1413:1433 recognized importance in the biogenesis and division of cell structures 1413:1483 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 6 13 contain has 1409:1411 arg1 organelle 1399:1407 this organelle 1394:1407 this organelle 1394:1407 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 5 14 theme chaperone 1207:1215 arg1 expression 1183:1192 the expression 1179:1192 the expression of the Hsp90 chaperone 1179:1215 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 2 15 used used 482:485 arg2 antibiotic 385:394 antibiotic 385:394 antibiotic 385:394 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 2 15 used used 482:485 arg2 inducer 503:509 an ER stress inducer 490:509 an ER stress inducer 490:509 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 2 15 used used 482:485 arg2 TM 375:376 TM 375:376 TM 375:376 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 2 15 used used 482:485 arg2 Tunicamycin 362:372 Tunicamycin 362:372 Tunicamycin (TM) 362:377 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 5 16 from stress 1067:1072 arg1 trypanosomatids 1077:1091 trypanosomatids 1077:1091 trypanosomatids 1077:1091 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 5 17 theme host 1152:1155 arg1 protozoan 1157:1165 the host protozoan 1148:1165 the host protozoan 1148:1165 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 5 18 from changes 1100:1106 arg1 composition 1119:1129 protein composition 1111:1129 protein composition 1111:1129 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 2 19 theme stress 496:501 arg1 Tunicamycin 362:372 Tunicamycin 362:372 Tunicamycin (TM) 362:377 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 2 19 theme stress 496:501 arg1 inducer 503:509 an ER stress inducer 490:509 an ER stress inducer 490:509 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 2 20 theme Protein 536:542 arg1 Response 544:551 the Unfolded Protein Response 523:551 the Unfolded Protein Response (UPR) 523:557 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 2 20 theme Protein 536:542 arg1 UPR 554:556 UPR 554:556 UPR 554:556 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 3 21 theme Mutualistic 560:570 arg1 symbiosis 572:580 Mutualistic symbiosis 560:580 Mutualistic symbiosis in trypanosomatids 560:599 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 3 22 from symbiosis 572:580 arg1 trypanosomatids 585:599 trypanosomatids 585:599 trypanosomatids 585:599 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 0 23 theme endoplasmic 14:24 arg1 reticulum 26:34 endoplasmic reticulum 14:34 the endoplasmic reticulum stressor tunicamycin 10:55 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 4 24 theme Golgi 934:938 arg1 cisternae 940:948 the ER and Golgi cisternae 923:948 cisternae 940:948 Cells treated with the inhibitor showed a decrease in proliferation, enlargement of the ER and Golgi cisternae and an increased distance between the symbiont and the ER. 35460679 2 25 theme N-linked 432:439 arg1 glycosylation 441:453 the N-linked glycosylation 428:453 the N-linked glycosylation in eukaryotes 428:467 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 3 26 theme Angomonas 743:751 arg1 deanei 753:758 Angomonas deanei 743:758 Angomonas deanei 743:758 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 6 27 theme associations 1328:1339 arg1 maintenance 1303:1313 maintenance 1303:1313 maintenance 1303:1313 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 6 27 theme associations 1328:1339 arg1 adaptation 1288:1297 adaptation 1288:1297 adaptation 1288:1297 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 3 28 theme metabolic 656:664 arg1 exchanges 666:674 intense metabolic exchanges 648:674 intense metabolic exchanges 648:674 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 1 29 theme unique 204:209 arg1 properties 211:220 unique properties 204:220 unique properties 204:220 The endoplasmic reticulum (ER) presents unique properties to establishing bacterium symbiosis in eukaryotic cells since it synthesizes and glycosylates essential molecules like proteins and lipids. 35460679 0 30 theme stressor 36:43 arg1 tunicamycin 45:55 the endoplasmic reticulum stressor tunicamycin 10:55 the endoplasmic reticulum stressor tunicamycin 10:55 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 1 31 theme essential 316:324 arg1 molecules 326:334 essential molecules 316:334 essential molecules like proteins and lipids 316:359 The endoplasmic reticulum (ER) presents unique properties to establishing bacterium symbiosis in eukaryotic cells since it synthesizes and glycosylates essential molecules like proteins and lipids. 35460679 0 32 theme endosymbiotic 139:151 arg1 bacterium 153:161 the endosymbiotic bacterium 135:161 the endosymbiotic bacterium 135:161 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 4 33 theme cisternae 940:948 arg1 distance 967:974 an increased distance 954:974 an increased distance between the symbiont and the ER 954:1006 Cells treated with the inhibitor showed a decrease in proliferation, enlargement of the ER and Golgi cisternae and an increased distance between the symbiont and the ER. 35460679 4 33 theme cisternae 940:948 arg1 enlargement 908:918 enlargement 908:918 enlargement of the ER and Golgi cisternae 908:948 Cells treated with the inhibitor showed a decrease in proliferation, enlargement of the ER and Golgi cisternae and an increased distance between the symbiont and the ER. 35460679 4 33 theme cisternae 940:948 arg1 proliferation 893:905 proliferation 893:905 proliferation 893:905 Cells treated with the inhibitor showed a decrease in proliferation, enlargement of the ER and Golgi cisternae and an increased distance between the symbiont and the ER. 35460679 0 34 theme reticulum 26:34 arg1 tunicamycin 45:55 the endoplasmic reticulum stressor tunicamycin 10:55 the endoplasmic reticulum stressor tunicamycin 10:55 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 3 35 from effects 702:708 arg1 association 723:733 the association 719:733 the association between Angomonas deanei and its symbiotic bacterium 719:786 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 2 36 theme Unfolded 527:534 arg1 Response 544:551 the Unfolded Protein Response 523:551 the Unfolded Protein Response (UPR) 523:557 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 2 36 theme Unfolded 527:534 arg1 UPR 554:556 UPR 554:556 UPR 554:556 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 6 37 theme symbiotic 1318:1326 arg1 associations 1328:1339 symbiotic associations 1318:1339 symbiotic associations between prokaryotes and eukaryotes 1318:1374 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 2 38 theme first 414:418 arg1 step 420:423 the first step 410:423 the first step in the N-linked glycosylation in eukaryotes 410:467 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 6 39 theme recognized 1413:1422 arg1 importance 1424:1433 recognized importance 1413:1433 recognized importance in the biogenesis and division of cell structures 1413:1483 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 6 40 dep biogenesis 1442:1451 arg1 the 1438:1440 the 1438:1440 the 1438:1440 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 2 41 theme ER 493:494 arg1 Tunicamycin 362:372 Tunicamycin 362:372 Tunicamycin (TM) 362:377 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 2 41 theme ER 493:494 arg1 inducer 503:509 an ER stress inducer 490:509 an ER stress inducer 490:509 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 4 42 dep symbiont 988:995 arg1 the 984:986 the 984:986 the 984:986 Cells treated with the inhibitor showed a decrease in proliferation, enlargement of the ER and Golgi cisternae and an increased distance between the symbiont and the ER. 35460679 0 43 theme tunicamycin 45:55 arg1 Effect 0:5 Effect 0:5 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 0:162 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 3 44 theme symbiotic 768:776 arg1 bacterium 778:786 its symbiotic bacterium 764:786 its symbiotic bacterium 764:786 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 5 45 theme protein 1111:1117 arg1 composition 1119:1129 protein composition 1111:1129 protein composition 1111:1129 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 3 46 theme intense 648:654 arg1 exchanges 666:674 intense metabolic exchanges 648:674 intense metabolic exchanges 648:674 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 5 47 theme important 1028:1036 arg1 TM 1009:1010 TM 1009:1010 TM 1009:1010 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 5 47 theme important 1028:1036 arg1 tool 1038:1041 an important tool 1025:1041 an important tool 1025:1041 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 4 48 theme ER 927:928 arg1 cisternae 940:948 the ER and Golgi cisternae 923:948 cisternae 940:948 Cells treated with the inhibitor showed a decrease in proliferation, enlargement of the ER and Golgi cisternae and an increased distance between the symbiont and the ER. 35460679 3 49 theme structural 621:630 arg1 adaptations 632:642 structural adaptations 621:642 structural adaptations 621:642 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 1 50 gly glycosylates 303:314 arg1 molecules 326:334 essential molecules 316:334 essential molecules like proteins and lipids 316:359 The endoplasmic reticulum (ER) presents unique properties to establishing bacterium symbiosis in eukaryotic cells since it synthesizes and glycosylates essential molecules like proteins and lipids. 35460679 5 51 located observed 1136:1143 arg1 protozoan 1157:1165 the host protozoan 1148:1165 the host protozoan 1148:1165 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 5 51 located observed 1136:1143 arg2 changes 1100:1106 changes 1100:1106 changes in protein composition 1100:1129 TM proved to be an important tool to better understand ER stress in trypanosomatids, since changes in protein composition were observed in the host protozoan, especially the expression of the Hsp90 chaperone. 35460679 3 52 theme proteomic 817:825 arg1 approaches 827:836 ultrastructural and proteomic approaches 797:836 ultrastructural and proteomic approaches 797:836 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 2 53 from step 420:423 arg1 glycosylation 441:453 the N-linked glycosylation 428:453 the N-linked glycosylation in eukaryotes 428:467 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 1 54 theme bacterium 238:246 arg1 symbiosis 248:256 bacterium symbiosis 238:256 bacterium symbiosis 238:256 The endoplasmic reticulum (ER) presents unique properties to establishing bacterium symbiosis in eukaryotic cells since it synthesizes and glycosylates essential molecules like proteins and lipids. 35460679 0 55 theme deanei 70:75 arg1 expression 96:105 Angomonas deanei heat-shock protein expression 60:105 Angomonas deanei heat-shock protein expression 60:105 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 6 56 from importance 1424:1433 arg1 biogenesis 1442:1451 biogenesis 1442:1451 biogenesis 1442:1451 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 6 56 from importance 1424:1433 arg1 division 1457:1464 division 1457:1464 division 1457:1464 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35460679 4 57 from decrease 881:888 arg1 distance 967:974 an increased distance 954:974 an increased distance between the symbiont and the ER 954:1006 Cells treated with the inhibitor showed a decrease in proliferation, enlargement of the ER and Golgi cisternae and an increased distance between the symbiont and the ER. 35460679 4 57 from decrease 881:888 arg1 enlargement 908:918 enlargement 908:918 enlargement of the ER and Golgi cisternae 908:948 Cells treated with the inhibitor showed a decrease in proliferation, enlargement of the ER and Golgi cisternae and an increased distance between the symbiont and the ER. 35460679 4 57 from decrease 881:888 arg1 proliferation 893:905 proliferation 893:905 proliferation 893:905 Cells treated with the inhibitor showed a decrease in proliferation, enlargement of the ER and Golgi cisternae and an increased distance between the symbiont and the ER. 35460679 0 58 with association 118:128 arg1 bacterium 153:161 the endosymbiotic bacterium 135:161 the endosymbiotic bacterium 135:161 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 3 59 theme ultrastructural 797:811 arg1 approaches 827:836 ultrastructural and proteomic approaches 797:836 ultrastructural and proteomic approaches 797:836 Mutualistic symbiosis in trypanosomatids is characterized by structural adaptations and intense metabolic exchanges, thus we investigated the effects of TM in the association between Angomonas deanei and its symbiotic bacterium, through ultrastructural and proteomic approaches. 35460679 0 60 theme Angomonas 60:68 arg1 expression 96:105 Angomonas deanei heat-shock protein expression 60:105 Angomonas deanei heat-shock protein expression 60:105 Effect of the endoplasmic reticulum stressor tunicamycin in Angomonas deanei heat-shock protein expression and on the association with the endosymbiotic bacterium. 35460679 2 61 from glycosylation 441:453 arg1 eukaryotes 458:467 eukaryotes 458:467 eukaryotes 458:467 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 2 62 gly glycosylation 441:453 arg1 eukaryotes 458:467 eukaryotes 458:467 eukaryotes 458:467 Tunicamycin (TM) is an antibiotic that inhibits the first step in the N-linked glycosylation in eukaryotes and has been used as an ER stress inducer to activate the Unfolded Protein Response (UPR). 35460679 6 63 dep adaptation 1288:1297 arg1 the 1284:1286 the 1284:1286 the 1284:1286 Furthermore, data obtained indicates the importance of the ER for the adaptation and maintenance of symbiotic associations between prokaryotes and eukaryotes, considering that this organelle has recognized importance in the biogenesis and division of cell structures. 35185292 9 0 contain contains 1576:1583 arg1 INFORMATION 1545:1555 SUPPLEMENTARY INFORMATION 1531:1555 SUPPLEMENTARY INFORMATION The online version 1531:1574 SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s10616-021-00501-3. 35185292 9 0 contain contains 1576:1583 arg2 material 1599:1606 supplementary material 1585:1606 supplementary material available at 10.1007/s10616-021-00501-3 1585:1646 SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s10616-021-00501-3. 35185292 4 1 theme Fc 604:605 arg1 region 607:612 the Fc region 600:612 the Fc region 600:612 Especially, afucosylation of the N-linked glycan in the Fc region is known to significantly increase antibody-dependent cellular cytotoxicity. 35185292 4 2 link N-linked 581:588 arg1 glycan 590:595 the N-linked glycan 577:595 the N-linked glycan 577:595 Especially, afucosylation of the N-linked glycan in the Fc region is known to significantly increase antibody-dependent cellular cytotoxicity. 35185292 1 3 theme next-generation 192:206 arg1 attention 179:187 attention 179:187 attention 179:187 Although antibodies have attracted attention as next-generation biopharmaceuticals, the costs of purifying the products and of arranging the environment for cell cultivation are high. 35185292 1 3 theme next-generation 192:206 arg1 biopharmaceuticals 208:225 next-generation biopharmaceuticals 192:225 next-generation biopharmaceuticals 192:225 Although antibodies have attracted attention as next-generation biopharmaceuticals, the costs of purifying the products and of arranging the environment for cell cultivation are high. 35185292 8 4 gly afucosylation 1282:1294 arg1 expression 1453:1462 the expression levels 1449:1469 the expression levels of other endogenous fucose metabolism-related enzyme genes 1449:1528 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 8 4 gly afucosylation 1282:1294 arg1 cell 1323:1326 cell growth 1323:1333 cell growth 1323:1333 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 8 4 gly afucosylation 1282:1294 arg1 glycans 1299:1305 glycans 1299:1305 glycans 1299:1305 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 8 4 gly afucosylation 1282:1294 arg1 genes 1524:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 1 5 theme cell 301:304 arg1 cultivation 306:316 cell cultivation 301:316 cell cultivation 301:316 Although antibodies have attracted attention as next-generation biopharmaceuticals, the costs of purifying the products and of arranging the environment for cell cultivation are high. 35185292 0 6 theme GDP-mannose-4,6-dehydratase 88:114 arg1 knockout 76:83 knockout 76:83 knockout 76:83 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 35185292 7 7 theme serum 1184:1188 arg1 presence 1172:1179 the presence 1168:1179 the presence of serum 1168:1188 We also demonstrated that, in culture in the presence of serum, fucosylation occurs due to contamination from serum components. 35185292 9 8 theme online 1561:1566 arg1 version 1568:1574 The online version 1557:1574 SUPPLEMENTARY INFORMATION The online version 1531:1574 SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s10616-021-00501-3. 35185292 6 9 theme fucosylated 1051:1061 arg1 glycans 1063:1069 no detected fucosylated glycans 1039:1069 no detected fucosylated glycans 1039:1069 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 0 10 theme transporter 131:141 arg1 knockout 76:83 knockout 76:83 knockout 76:83 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 35185292 8 11 theme other 1474:1478 arg1 genes 1524:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 5 12 theme protein 892:898 arg1 production 900:909 biopharmaceutical protein production 874:909 biopharmaceutical protein production 874:909 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 4 13 theme antibody-dependent 649:666 arg1 cytotoxicity 677:688 antibody-dependent cellular cytotoxicity 649:688 antibody-dependent cellular cytotoxicity 649:688 Especially, afucosylation of the N-linked glycan in the Fc region is known to significantly increase antibody-dependent cellular cytotoxicity. 35185292 5 14 theme hamster 838:844 arg1 cells 852:856 Chinese hamster ovary cells 830:856 Chinese hamster ovary cells 830:856 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 5 14 theme hamster 838:844 arg1 platform 861:868 a platform 859:868 a platform for biopharmaceutical protein production 859:909 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 0 15 theme GDP-fucose 120:129 arg1 transporter 131:141 GDP-fucose transporter 120:141 GDP-fucose transporter 120:141 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 35185292 6 16 theme serum-free 942:951 arg1 medium 953:958 serum-free medium 942:958 serum-free medium 942:958 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 5 17 theme Chinese 830:836 arg1 cells 852:856 Chinese hamster ovary cells 830:856 Chinese hamster ovary cells 830:856 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 5 17 theme Chinese 830:836 arg1 platform 861:868 a platform 859:868 a platform for biopharmaceutical protein production 859:909 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 9 18 theme available 1608:1616 arg1 material 1599:1606 supplementary material 1585:1606 supplementary material available at 10.1007/s10616-021-00501-3 1585:1646 SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s10616-021-00501-3. 35185292 8 19 theme wild-type 1388:1396 arg1 cells 1402:1406 wild-type CHO cells 1388:1406 wild-type CHO cells 1388:1406 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 5 20 theme GDP-fucose 787:796 arg1 transporter 798:808 GDP-fucose transporter 787:808 GDP-fucose transporter 787:808 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 6 21 theme detected 1042:1049 arg1 glycans 1063:1069 no detected fucosylated glycans 1039:1069 no detected fucosylated glycans 1039:1069 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 8 22 theme cell 1323:1326 arg1 growth 1328:1333 cell growth 1323:1333 cell growth 1323:1333 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 6 23 theme suspension-cultured 977:995 arg1 cells 997:1001 suspension-cultured cells 977:1001 suspension-cultured cells 977:1001 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 4 24 theme N-linked 581:588 arg1 glycan 590:595 the N-linked glycan 577:595 the N-linked glycan 577:595 Especially, afucosylation of the N-linked glycan in the Fc region is known to significantly increase antibody-dependent cellular cytotoxicity. 35185292 0 25 theme adapted 28:34 arg1 cells 58:62 serum-free adapted Chinese hamster ovary cells 17:62 serum-free adapted Chinese hamster ovary cells 17:62 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 35185292 8 26 theme genes 1524:1528 arg1 levels 1464:1469 the expression levels 1449:1469 the expression levels of other endogenous fucose metabolism-related enzyme genes 1449:1528 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 7 27 gly fucosylation 1191:1202 arg2 culture 1157:1163 culture 1157:1163 culture in the presence of serum 1157:1188 We also demonstrated that, in culture in the presence of serum, fucosylation occurs due to contamination from serum components. 35185292 8 28 theme expression 1453:1462 arg1 levels 1464:1469 the expression levels 1449:1469 the expression levels of other endogenous fucose metabolism-related enzyme genes 1449:1528 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 9 29 dep INFORMATION 1545:1555 arg1 version 1568:1574 The online version 1557:1574 SUPPLEMENTARY INFORMATION The online version 1531:1574 SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s10616-021-00501-3. 35185292 4 30 theme cellular 668:675 arg1 cytotoxicity 677:688 antibody-dependent cellular cytotoxicity 649:688 antibody-dependent cellular cytotoxicity 649:688 Especially, afucosylation of the N-linked glycan in the Fc region is known to significantly increase antibody-dependent cellular cytotoxicity. 35185292 0 31 theme serum-free 17:26 arg1 cells 58:62 serum-free adapted Chinese hamster ovary cells 17:62 serum-free adapted Chinese hamster ovary cells 17:62 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 35185292 8 32 theme CHO 1398:1400 arg1 cells 1402:1406 wild-type CHO cells 1388:1406 wild-type CHO cells 1388:1406 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 2 33 theme product 397:403 arg1 quality 405:411 product quality 397:411 product quality 397:411 Therefore, there is a need to increase antibody efficacy and improve product quality as much as possible. 35185292 0 34 theme hamster 44:50 arg1 cells 58:62 serum-free adapted Chinese hamster ovary cells 17:62 serum-free adapted Chinese hamster ovary cells 17:62 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 35185292 4 35 theme glycan 590:595 arg1 afucosylation 560:572 afucosylation 560:572 afucosylation of the N-linked glycan in the Fc region 560:612 Especially, afucosylation of the N-linked glycan in the Fc region is known to significantly increase antibody-dependent cellular cytotoxicity. 35185292 6 36 theme ΔGMDΔGFT 924:931 arg1 cells 933:937 ΔGMDΔGFT cells 924:937 ΔGMDΔGFT cells 924:937 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 5 37 theme GDP-mannose 755:765 arg1 4,6-dehydratase 767:781 GDP-mannose 4,6-dehydratase 755:781 GDP-mannose 4,6-dehydratase 755:781 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 3 38 theme glycan 476:481 arg1 structures 483:492 their glycan structures 470:492 their glycan structures 470:492 Since antibodies are glycoproteins, their glycan structures have been found to affect the function of antibodies. 35185292 0 39 theme Chinese 36:42 arg1 cells 58:62 serum-free adapted Chinese hamster ovary cells 17:62 serum-free adapted Chinese hamster ovary cells 17:62 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 35185292 6 40 theme CHO 1024:1026 arg1 cells 1028:1032 host CHO cells 1019:1032 host CHO cells 1019:1032 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 4 41 from afucosylation 560:572 arg1 region 607:612 the Fc region 600:612 the Fc region 600:612 Especially, afucosylation of the N-linked glycan in the Fc region is known to significantly increase antibody-dependent cellular cytotoxicity. 35185292 1 42 dep costs 232:236 arg1 arranging 271:279 arranging 271:279 arranging the environment for cell cultivation 271:316 Although antibodies have attracted attention as next-generation biopharmaceuticals, the costs of purifying the products and of arranging the environment for cell cultivation are high. 35185292 1 42 dep costs 232:236 arg1 purifying 241:249 purifying 241:249 purifying the products 241:262 Although antibodies have attracted attention as next-generation biopharmaceuticals, the costs of purifying the products and of arranging the environment for cell cultivation are high. 35185292 6 43 theme antibodies 1115:1124 arg1 production 1088:1097 production 1088:1097 production of afucosylated antibodies 1088:1124 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 0 44 theme cells 58:62 arg1 Establishment 0:12 Establishment 0:12 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 0:142 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 35185292 6 45 theme host 1019:1022 arg1 cells 1028:1032 host CHO cells 1019:1032 host CHO cells 1019:1032 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 8 46 theme endogenous 1480:1489 arg1 genes 1524:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 7 47 from components 1243:1252 arg1 contamination 1218:1230 contamination 1218:1230 contamination from serum components 1218:1252 We also demonstrated that, in culture in the presence of serum, fucosylation occurs due to contamination from serum components. 35185292 2 48 theme antibody 367:374 arg1 efficacy 376:383 antibody efficacy 367:383 antibody efficacy 367:383 Therefore, there is a need to increase antibody efficacy and improve product quality as much as possible. 35185292 0 49 theme ovary 52:56 arg1 cells 58:62 serum-free adapted Chinese hamster ovary cells 17:62 serum-free adapted Chinese hamster ovary cells 17:62 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 35185292 7 50 from culture 1157:1163 arg1 presence 1172:1179 the presence 1168:1179 the presence of serum 1168:1188 We also demonstrated that, in culture in the presence of serum, fucosylation occurs due to contamination from serum components. 35185292 8 51 theme enzyme 1517:1522 arg1 genes 1524:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 6 52 gly fucosylated 1051:1061 arg1 glycans 1063:1069 no detected fucosylated glycans 1039:1069 no detected fucosylated glycans 1039:1069 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 8 53 theme serum-free 1355:1364 arg1 medium 1366:1371 serum-free medium 1355:1371 serum-free medium 1355:1371 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 6 54 gly afucosylated 1102:1113 arg1 antibodies 1115:1124 afucosylated antibodies 1102:1124 afucosylated antibodies 1102:1124 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 8 55 theme metabolism-related 1498:1515 arg1 genes 1524:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 0 56 with Establishment 0:12 arg1 knockout 76:83 knockout 76:83 knockout 76:83 Establishment of serum-free adapted Chinese hamster ovary cells with double knockout of GDP-mannose-4,6-dehydratase and GDP-fucose transporter. 35185292 6 57 theme afucosylated 1102:1113 arg1 antibodies 1115:1124 afucosylated antibodies 1102:1124 afucosylated antibodies 1102:1124 By adapting ΔGMDΔGFT cells to serum-free medium and constructing suspension-cultured cells, we established host CHO cells with no detected fucosylated glycans and succeeded in production of afucosylated antibodies. 35185292 5 58 theme double-mutant 723:735 arg1 ΔGMDΔGFT 737:744 a double-mutant ΔGMDΔGFT 721:744 a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production 721:909 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 8 59 theme fucose 1491:1496 arg1 genes 1524:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 other endogenous fucose metabolism-related enzyme genes 1474:1528 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 8 60 theme glycans 1299:1305 arg1 afucosylation 1282:1294 afucosylation 1282:1294 afucosylation of glycans 1282:1305 Furthermore, we found that afucosylation of glycans does not affect cell growth after adaptation to serum-free medium as compared to wild-type CHO cells growth and does not significantly affect the expression levels of other endogenous fucose metabolism-related enzyme genes. 35185292 9 61 theme supplementary 1585:1597 arg1 material 1599:1606 supplementary material 1585:1606 supplementary material available at 10.1007/s10616-021-00501-3 1585:1646 SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s10616-021-00501-3. 35185292 3 62 gly glycoproteins 455:467 arg1 glycoproteins 455:467 glycoproteins 455:467 glycoproteins 455:467 Since antibodies are glycoproteins, their glycan structures have been found to affect the function of antibodies. 35185292 3 62 gly glycoproteins 455:467 arg1 antibodies 440:449 antibodies 440:449 antibodies 440:449 Since antibodies are glycoproteins, their glycan structures have been found to affect the function of antibodies. 35185292 5 63 theme biopharmaceutical 874:890 arg1 production 900:909 biopharmaceutical protein production 874:909 biopharmaceutical protein production 874:909 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 3 64 theme antibodies 536:545 arg1 function 524:531 the function 520:531 the function of antibodies 520:545 Since antibodies are glycoproteins, their glycan structures have been found to affect the function of antibodies. 35185292 9 65 theme SUPPLEMENTARY 1531:1543 arg1 INFORMATION 1545:1555 SUPPLEMENTARY INFORMATION 1531:1555 SUPPLEMENTARY INFORMATION The online version 1531:1574 SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s10616-021-00501-3. 35185292 5 66 theme ovary 846:850 arg1 cells 852:856 Chinese hamster ovary cells 830:856 Chinese hamster ovary cells 830:856 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 5 66 theme ovary 846:850 arg1 platform 861:868 a platform 859:868 a platform for biopharmaceutical protein production 859:909 In this study, we established a double-mutant ΔGMDΔGFT in which GDP-mannose 4,6-dehydratase and GDP-fucose transporter were knocked out in Chinese hamster ovary cells, a platform for biopharmaceutical protein production. 35185292 7 67 theme serum 1237:1241 arg1 components 1243:1252 serum components 1237:1252 serum components 1237:1252 We also demonstrated that, in culture in the presence of serum, fucosylation occurs due to contamination from serum components. 35185292 4 68 gly afucosylation 560:572 arg1 region 607:612 the Fc region 600:612 the Fc region 600:612 Especially, afucosylation of the N-linked glycan in the Fc region is known to significantly increase antibody-dependent cellular cytotoxicity. 35185292 4 68 gly afucosylation 560:572 arg1 glycan 590:595 the N-linked glycan 577:595 the N-linked glycan 577:595 Especially, afucosylation of the N-linked glycan in the Fc region is known to significantly increase antibody-dependent cellular cytotoxicity. 35185292 9 69 from 10.1007/s10616-021-00501-3 1621:1646 arg1 available 1608:1616 available 1608:1616 available 1608:1616 SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s10616-021-00501-3. 37065091 1 0 from breathing 169:177 arg1 population 195:204 the affected population 182:204 the affected population 182:204 High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. 37065091 7 1 theme potential 1295:1303 arg1 targets 1305:1311 potential targets 1295:1311 potential targets to ameliorate acute lung injury 1295:1343 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 7 2 theme lung 1333:1336 arg1 injury 1338:1343 acute lung injury 1327:1343 acute lung injury 1327:1343 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 6 3 theme multiple 998:1005 arg1 pathways 1007:1014 multiple pathways 998:1014 multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation 998:1095 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 6 4 theme amino 1029:1033 arg1 metabolism 1040:1049 amino acid metabolism 1029:1049 amino acid metabolism 1029:1049 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 5 5 theme post-spinal 823:833 arg1 injury 840:845 lung injury two weeks post-spinal cord injury 801:845 lung injury two weeks post-spinal cord injury 801:845 We demonstrate that animals display some early signs of lung injury two weeks post-spinal cord injury. 37065091 7 6 theme injury 1160:1165 arg1 model 1146:1150 a model 1144:1150 a model of lung injury after spinal cord injury 1144:1190 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 5 7 theme early 786:790 arg1 signs 792:796 some early signs 781:796 some early signs of lung injury two weeks post-spinal cord injury 781:845 We demonstrate that animals display some early signs of lung injury two weeks post-spinal cord injury. 37065091 6 8 from dysregulation 981:993 arg1 pathways 1007:1014 multiple pathways 998:1014 multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation 998:1095 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 3 9 theme acute 368:372 arg1 injury 379:384 acute lung injury 368:384 acute lung injury 368:384 While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. 37065091 2 10 theme lung 281:284 arg1 injury 286:291 acute lung injury 275:291 acute lung injury 275:291 Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. 37065091 3 11 theme relationship 528:539 arg1 biology 512:518 the fundamental biology 496:518 the fundamental biology of this relationship 496:539 While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. 37065091 5 12 theme weeks 817:821 arg1 injury 840:845 lung injury two weeks post-spinal cord injury 801:845 lung injury two weeks post-spinal cord injury 801:845 We demonstrate that animals display some early signs of lung injury two weeks post-spinal cord injury. 37065091 7 13 theme acute 1327:1331 arg1 injury 1338:1343 acute lung injury 1327:1343 acute lung injury 1327:1343 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 0 14 from injury 37:42 arg1 lungs 74:78 the lungs 70:78 the lungs 70:78 Cervical spinal cord injury leads to injury and altered metabolism in the lungs. 37065091 2 15 theme acute 275:279 arg1 injury 286:291 acute lung injury 275:291 acute lung injury 275:291 Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. 37065091 6 16 theme metabolic 971:979 arg1 dysregulation 981:993 metabolic dysregulation 971:993 metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation 971:1095 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 4 17 theme adult 733:737 arg1 rats 739:742 adult rats 733:742 adult rats 733:742 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 3 18 theme spinal 390:395 arg1 injury 402:407 spinal cord injury 390:407 spinal cord injury 390:407 While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. 37065091 3 19 theme animal 468:473 arg1 model 475:479 an animal model 465:479 an animal model to interrogate the fundamental biology of this relationship 465:539 While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. 37065091 3 20 theme clinical 431:438 arg1 setting 440:446 the clinical setting 427:446 the clinical setting 427:446 While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. 37065091 0 21 theme spinal 9:14 arg1 injury 21:26 Cervical spinal cord injury 0:26 Cervical spinal cord injury 0:26 Cervical spinal cord injury leads to injury and altered metabolism in the lungs. 37065091 3 22 theme fundamental 500:510 arg1 biology 512:518 the fundamental biology 496:518 the fundamental biology of this relationship 496:539 While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. 37065091 7 23 theme cord 1180:1183 arg1 injury 1185:1190 spinal cord injury 1173:1190 spinal cord injury 1173:1190 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 2 24 theme substantial 309:319 arg1 rates 331:335 substantial mortality rates 309:335 substantial mortality rates 309:335 Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. 37065091 6 25 theme dysregulation 981:993 arg1 signs 962:966 significant signs 950:966 significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation 950:1095 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 7 26 theme acute 1198:1202 arg1 point 1209:1213 an acute time point 1195:1213 an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury 1195:1343 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 0 27 theme Cervical 0:7 arg1 injury 21:26 Cervical spinal cord injury 0:26 Cervical spinal cord injury 0:26 Cervical spinal cord injury leads to injury and altered metabolism in the lungs. 37065091 6 28 theme histological 865:876 arg1 signs 878:882 no obvious histological signs 854:882 no obvious histological signs of injury 854:892 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 4 29 theme = 676:676 arg1 injury 666:671 sham injury 661:671 sham injury (N = 3) 661:679 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 4 29 theme = 676:676 arg1 N 674:674 N = 3 674:678 N = 3 674:678 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 7 30 theme lung 1262:1265 arg1 damage 1267:1272 lung damage 1262:1272 lung damage 1262:1272 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 6 31 theme significant 950:960 arg1 signs 962:966 significant signs 950:966 significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation 950:1095 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 3 32 theme lung 374:377 arg1 injury 379:384 acute lung injury 368:384 acute lung injury 368:384 While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. 37065091 6 33 theme obvious 857:863 arg1 signs 878:882 no obvious histological signs 854:882 no obvious histological signs of injury 854:892 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 3 34 located found 418:422 arg2 correlation 348:358 the correlation 344:358 the correlation between acute lung injury and spinal cord injury 344:407 While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. 37065091 3 34 located found 418:422 arg1 setting 440:446 the clinical setting 427:446 the clinical setting 427:446 While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. 37065091 1 35 theme High-cervical 81:93 arg1 cord 102:105 High-cervical spinal cord 81:105 High-cervical spinal cord injury 81:112 High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. 37065091 6 36 from signs 962:966 arg1 pathways 1007:1014 multiple pathways 998:1014 multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation 998:1095 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 1 37 theme affected 186:193 arg1 population 195:204 the affected population 182:204 the affected population 182:204 High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. 37065091 0 38 theme cord 16:19 arg1 injury 21:26 Cervical spinal cord injury 0:26 Cervical spinal cord injury 0:26 Cervical spinal cord injury leads to injury and altered metabolism in the lungs. 37065091 7 39 used used 1227:1230 arg2 point 1209:1213 an acute time point 1195:1213 an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury 1195:1343 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 5 40 theme cord 835:838 arg1 injury 840:845 lung injury two weeks post-spinal cord injury 801:845 lung injury two weeks post-spinal cord injury 801:845 We demonstrate that animals display some early signs of lung injury two weeks post-spinal cord injury. 37065091 1 41 theme spinal 95:100 arg1 cord 102:105 High-cervical spinal cord 81:105 High-cervical spinal cord injury 81:112 High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. 37065091 6 42 theme lipid 1052:1056 arg1 metabolism 1058:1067 lipid metabolism 1052:1067 lipid metabolism 1052:1067 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 5 43 theme injury 806:811 arg1 injury 840:845 lung injury two weeks post-spinal cord injury 801:845 lung injury two weeks post-spinal cord injury 801:845 We demonstrate that animals display some early signs of lung injury two weeks post-spinal cord injury. 37065091 6 44 theme injured 925:931 arg1 cohort 933:938 the spinal cord injured cohort 909:938 the spinal cord injured cohort 909:938 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 4 45 theme lung 718:721 arg1 injury 723:728 lung injury 718:728 lung injury in adult rats 718:742 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 7 46 theme time 1204:1207 arg1 point 1209:1213 an acute time point 1195:1213 an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury 1195:1343 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 4 47 theme spinal 623:628 arg1 cord 630:633 cervical spinal cord 614:633 an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) 598:706 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 6 48 theme injury 887:892 arg1 signs 878:882 no obvious histological signs 854:882 no obvious histological signs of injury 854:892 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 0 49 from metabolism 56:65 arg1 lungs 74:78 the lungs 70:78 the lungs 70:78 Cervical spinal cord injury leads to injury and altered metabolism in the lungs. 37065091 2 50 theme injured 228:234 arg1 individuals 236:246 cervically injured individuals 217:246 cervically injured individuals 217:246 Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. 37065091 4 51 theme cervical 614:621 arg1 cord 630:633 cervical spinal cord 614:633 an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) 598:706 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 3 52 theme cord 397:400 arg1 injury 402:407 spinal cord injury 390:407 spinal cord injury 390:407 While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. 37065091 4 53 theme naïve 685:689 arg1 animals 691:697 naïve animals 685:697 naïve animals (N = 15) 685:706 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 4 53 theme naïve 685:689 arg1 N 700:700 N = 15 700:705 N = 15 700:705 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 4 54 from injury 723:728 arg1 rats 739:742 adult rats 733:742 adult rats 733:742 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 1 55 theme cord 102:105 arg1 injury 107:112 High-cervical spinal cord injury 81:112 High-cervical spinal cord injury 81:112 High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. 37065091 6 56 theme N-linked 1074:1081 arg1 glycosylation 1083:1095 N-linked glycosylation 1074:1095 N-linked glycosylation 1074:1095 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 7 57 theme damage 1267:1272 arg1 progression 1247:1257 the progression 1243:1257 the progression of lung damage 1243:1272 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 4 58 theme sham 661:664 arg1 injury 666:671 sham injury 661:671 sham injury (N = 3) 661:679 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 4 58 theme sham 661:664 arg1 N 674:674 N = 3 674:678 N = 3 674:678 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 4 59 theme = 645:645 arg1 injury 635:640 an experimental cervical spinal cord injury 598:640 an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) 598:706 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 4 59 theme = 645:645 arg1 N 643:643 N = 18 643:648 N = 18 643:648 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 7 60 theme lung 1155:1158 arg1 injury 1160:1165 lung injury 1155:1165 lung injury after spinal cord injury 1155:1190 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 5 61 theme injury 840:845 arg1 signs 792:796 some early signs 781:796 some early signs of lung injury two weeks post-spinal cord injury 781:845 We demonstrate that animals display some early signs of lung injury two weeks post-spinal cord injury. 37065091 6 62 theme spinal 913:918 arg1 cord 920:923 the spinal cord 909:923 the spinal cord injured cohort 909:938 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 5 63 theme lung 801:804 arg1 injury 840:845 lung injury two weeks post-spinal cord injury 801:845 lung injury two weeks post-spinal cord injury 801:845 We demonstrate that animals display some early signs of lung injury two weeks post-spinal cord injury. 37065091 4 64 theme = 702:702 arg1 animals 691:697 naïve animals 685:697 naïve animals (N = 15) 685:706 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 4 64 theme = 702:702 arg1 N 700:700 N = 15 700:705 N = 15 700:705 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 2 65 theme mortality 321:329 arg1 rates 331:335 substantial mortality rates 309:335 substantial mortality rates 309:335 Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. 37065091 6 66 theme acid 1035:1038 arg1 metabolism 1040:1049 amino acid metabolism 1029:1049 amino acid metabolism 1029:1049 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 7 67 theme first 1133:1137 arg1 time 1139:1142 the first time 1129:1142 the first time 1129:1142 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 6 68 theme cord 920:923 arg1 cohort 933:938 the spinal cord injured cohort 909:938 the spinal cord injured cohort 909:938 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 4 69 theme experimental 601:612 arg1 injury 635:640 an experimental cervical spinal cord injury 598:640 an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) 598:706 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 4 69 theme experimental 601:612 arg1 N 643:643 N = 18 643:648 N = 18 643:648 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 1 70 theme respiratory 129:139 arg1 pathways 147:154 respiratory motor pathways 129:154 respiratory motor pathways 129:154 High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. 37065091 4 71 theme cord 630:633 arg1 injury 635:640 an experimental cervical spinal cord injury 598:640 an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) 598:706 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 4 71 theme cord 630:633 arg1 N 643:643 N = 18 643:648 N = 18 643:648 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 37065091 0 72 theme altered 48:54 arg1 metabolism 56:65 altered metabolism 48:65 altered metabolism 48:65 Cervical spinal cord injury leads to injury and altered metabolism in the lungs. 37065091 6 73 link N-linked 1074:1081 arg1 glycosylation 1083:1095 N-linked glycosylation 1074:1095 N-linked glycosylation 1074:1095 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 6 74 from pathways 1007:1014 arg1 signs 962:966 significant signs 950:966 significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation 950:1095 While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. 37065091 1 75 theme motor 141:145 arg1 pathways 147:154 respiratory motor pathways 129:154 respiratory motor pathways 129:154 High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. 37065091 7 76 theme spinal 1173:1178 arg1 injury 1185:1190 spinal cord injury 1173:1190 spinal cord injury 1173:1190 Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury. 37065091 4 77 from gap 567:569 arg1 knowledge 574:582 knowledge 574:582 knowledge 574:582 To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. 36866557 4 0 theme enzyme 592:597 arg1 therapy 611:617 novel enzyme replacement therapy 586:617 novel enzyme replacement therapy 586:617 METHODS In this work, we determined the levels of urinary mannose-rich oligosaccharides in a patient subjected to novel enzyme replacement therapy. 36866557 4 1 from levels 512:517 arg1 patient 565:571 a patient 563:571 a patient subjected to novel enzyme replacement therapy 563:617 METHODS In this work, we determined the levels of urinary mannose-rich oligosaccharides in a patient subjected to novel enzyme replacement therapy. 36866557 4 2 dep METHODS 472:478 arg1 determined 497:506 determined 497:506 determined the levels of urinary mannose-rich oligosaccharides in a patient subjected to novel enzyme replacement therapy 497:617 METHODS In this work, we determined the levels of urinary mannose-rich oligosaccharides in a patient subjected to novel enzyme replacement therapy. 36866557 11 3 theme 7-9 1637:1639 arg1 units 1649:1653 7-9 mannose units 1637:1653 7-9 mannose units 1637:1653 A significant decrease in the levels of oligosaccharides with 7-9 mannose units was detected by HPLC. 36866557 2 4 theme N-linked 282:289 arg1 oligosaccharides 291:306 N-linked oligosaccharides 282:306 N-linked oligosaccharides 282:306 This enzyme is involved in the hydrolysis of mannosidic linkages in N-linked oligosaccharides. 36866557 9 5 theme therapy 1270:1276 arg1 administration 1252:1265 the administration 1248:1265 the administration of therapy 1248:1276 RESULTS Compared to levels before the administration of therapy, an approximately two-folds decrease in total mannose-rich oligosaccharides after one month of treatment was observed by NMR and HPLC. 36866557 2 6 theme linkages 270:277 arg1 hydrolysis 245:254 the hydrolysis 241:254 the hydrolysis of mannosidic linkages in N-linked oligosaccharides 241:306 This enzyme is involved in the hydrolysis of mannosidic linkages in N-linked oligosaccharides. 36866557 6 7 theme desorption/ionization 901:921 arg1 MALDI-TOF/TOF 954:966 MALDI-TOF/TOF 954:966 MALDI-TOF/TOF 954:966 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 6 7 theme desorption/ionization 901:921 arg1 spectrometry 974:985 matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry 879:985 matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry 879:985 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 5 8 theme phase 672:676 arg1 SPE 690:692 SPE 690:692 SPE 690:692 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 5 8 theme phase 672:676 arg1 extraction 678:687 solid phase extraction 666:687 solid phase extraction (SPE) 666:693 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 10 9 theme urinary 1489:1495 arg1 oligosaccharides 1510:1525 total urinary mannose-rich oligosaccharides 1483:1525 total urinary mannose-rich oligosaccharides 1483:1525 After four months, an approximately ten-folds significant decrease in total urinary mannose-rich oligosaccharides was detected, suggesting therapy effectiveness. 36866557 9 10 theme two-folds 1296:1304 arg1 decrease 1306:1313 an approximately two-folds decrease 1279:1313 an approximately two-folds decrease in total mannose-rich oligosaccharides after one month of treatment 1279:1381 RESULTS Compared to levels before the administration of therapy, an approximately two-folds decrease in total mannose-rich oligosaccharides after one month of treatment was observed by NMR and HPLC. 36866557 1 11 theme α-D-mannosidase 197:211 arg1 activity 185:192 decreased activity 175:192 decreased activity of α-D-mannosidase 175:211 BACKGROUND Alpha-mannosidosis is a rare lysosomal storage disorder, caused by decreased activity of α-D-mannosidase. 36866557 7 12 theme nuclear 1080:1086 arg1 NMR 1108:1110 NMR 1108:1110 NMR 1108:1110 In addition, the levels of urinary mannose-rich oligosaccharides were also quantified by 1H nuclear magnetic resonance (NMR) spectroscopy. 36866557 7 12 theme nuclear 1080:1086 arg1 resonance 1097:1105 1H nuclear magnetic resonance 1077:1105 1H nuclear magnetic resonance (NMR) spectroscopy 1077:1124 In addition, the levels of urinary mannose-rich oligosaccharides were also quantified by 1H nuclear magnetic resonance (NMR) spectroscopy. 36866557 0 13 from Monitoring 43:52 arg1 Alpha-Mannosidosis 77:94 Alpha-Mannosidosis 77:94 Alpha-Mannosidosis 77:94 The Application of HPLC-FLD and NMR in the Monitoring of Therapy Efficacy in Alpha-Mannosidosis. 36866557 9 14 theme mannose-rich 1324:1335 arg1 oligosaccharides 1337:1352 total mannose-rich oligosaccharides 1318:1352 total mannose-rich oligosaccharides 1318:1352 RESULTS Compared to levels before the administration of therapy, an approximately two-folds decrease in total mannose-rich oligosaccharides after one month of treatment was observed by NMR and HPLC. 36866557 12 15 theme efficacy 1827:1834 arg1 monitoring 1805:1814 monitoring 1805:1814 monitoring of therapy efficacy in alpha-mannosidosis patients 1805:1865 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 7 16 theme 1H 1077:1078 arg1 NMR 1108:1110 NMR 1108:1110 NMR 1108:1110 In addition, the levels of urinary mannose-rich oligosaccharides were also quantified by 1H nuclear magnetic resonance (NMR) spectroscopy. 36866557 7 16 theme 1H 1077:1078 arg1 resonance 1097:1105 1H nuclear magnetic resonance 1077:1105 1H nuclear magnetic resonance (NMR) spectroscopy 1077:1124 In addition, the levels of urinary mannose-rich oligosaccharides were also quantified by 1H nuclear magnetic resonance (NMR) spectroscopy. 36866557 1 17 theme rare 132:135 arg1 Alpha-mannosidosis 108:125 BACKGROUND Alpha-mannosidosis 97:125 BACKGROUND Alpha-mannosidosis 97:125 BACKGROUND Alpha-mannosidosis is a rare lysosomal storage disorder, caused by decreased activity of α-D-mannosidase. 36866557 1 17 theme rare 132:135 arg1 disorder 155:162 a rare lysosomal storage disorder 130:162 a rare lysosomal storage disorder 130:162 BACKGROUND Alpha-mannosidosis is a rare lysosomal storage disorder, caused by decreased activity of α-D-mannosidase. 36866557 12 18 theme alpha-mannosidosis 1839:1856 arg1 patients 1858:1865 alpha-mannosidosis patients 1839:1865 alpha-mannosidosis patients 1839:1865 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 5 19 with chromatography 783:796 arg1 detector 823:830 fluorescence detector 810:830 fluorescence detector (FLD) 810:836 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 5 19 with chromatography 783:796 arg1 FLD 833:835 FLD 833:835 FLD 833:835 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 7 20 theme oligosaccharides 1036:1051 arg1 levels 1005:1010 the levels 1001:1010 the levels of urinary mannose-rich oligosaccharides 1001:1051 In addition, the levels of urinary mannose-rich oligosaccharides were also quantified by 1H nuclear magnetic resonance (NMR) spectroscopy. 36866557 1 21 theme storage 147:153 arg1 Alpha-mannosidosis 108:125 BACKGROUND Alpha-mannosidosis 97:125 BACKGROUND Alpha-mannosidosis 97:125 BACKGROUND Alpha-mannosidosis is a rare lysosomal storage disorder, caused by decreased activity of α-D-mannosidase. 36866557 1 21 theme storage 147:153 arg1 disorder 155:162 a rare lysosomal storage disorder 130:162 a rare lysosomal storage disorder 130:162 BACKGROUND Alpha-mannosidosis is a rare lysosomal storage disorder, caused by decreased activity of α-D-mannosidase. 36866557 3 22 theme mannosidase 320:330 arg1 defect 332:337 the mannosidase defect 316:337 the mannosidase defect 316:337 Due to the mannosidase defect, undigested mannose-rich oligosaccharides (Man2GlcNAc - Man9GlcNAc) accumulating in cells are excreted in large quantities in urine. 36866557 5 23 theme fluorescent 707:717 arg1 2-aminobenzamide 723:738 fluorescent tag 2-aminobenzamide 707:738 fluorescent tag 2-aminobenzamide 707:738 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 0 24 theme Therapy 57:63 arg1 Efficacy 65:72 Therapy Efficacy 57:72 Therapy Efficacy 57:72 The Application of HPLC-FLD and NMR in the Monitoring of Therapy Efficacy in Alpha-Mannosidosis. 36866557 9 25 theme treatment 1373:1381 arg1 month 1364:1368 one month 1360:1368 one month of treatment 1360:1381 RESULTS Compared to levels before the administration of therapy, an approximately two-folds decrease in total mannose-rich oligosaccharides after one month of treatment was observed by NMR and HPLC. 36866557 7 26 theme urinary 1015:1021 arg1 oligosaccharides 1036:1051 urinary mannose-rich oligosaccharides 1015:1051 urinary mannose-rich oligosaccharides 1015:1051 In addition, the levels of urinary mannose-rich oligosaccharides were also quantified by 1H nuclear magnetic resonance (NMR) spectroscopy. 36866557 10 27 theme significant 1459:1469 arg1 decrease 1471:1478 an approximately ten-folds significant decrease 1432:1478 an approximately ten-folds significant decrease in total urinary mannose-rich oligosaccharides 1432:1525 After four months, an approximately ten-folds significant decrease in total urinary mannose-rich oligosaccharides was detected, suggesting therapy effectiveness. 36866557 3 28 theme mannose-rich 351:362 arg1 oligosaccharides 364:379 undigested mannose-rich oligosaccharides 340:379 undigested mannose-rich oligosaccharides (Man2GlcNAc - Man9GlcNAc) accumulating in cells 340:427 Due to the mannosidase defect, undigested mannose-rich oligosaccharides (Man2GlcNAc - Man9GlcNAc) accumulating in cells are excreted in large quantities in urine. 36866557 5 29 theme liquid 776:781 arg1 HPLC 799:802 HPLC 799:802 HPLC 799:802 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 5 29 theme liquid 776:781 arg1 chromatography 783:796 high-performance liquid chromatography 759:796 high-performance liquid chromatography (HPLC) with fluorescence detector (FLD) 759:836 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 12 30 theme suitable 1783:1790 arg1 application 1693:1703 The application 1689:1703 The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers 1689:1776 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 12 30 theme suitable 1783:1790 arg1 approach 1792:1799 a suitable approach 1781:1799 a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients 1781:1865 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 11 31 from decrease 1589:1596 arg1 levels 1605:1610 the levels 1601:1610 the levels of oligosaccharides with 7-9 mannose units 1601:1653 A significant decrease in the levels of oligosaccharides with 7-9 mannose units was detected by HPLC. 36866557 2 32 from hydrolysis 245:254 arg1 oligosaccharides 291:306 N-linked oligosaccharides 282:306 N-linked oligosaccharides 282:306 This enzyme is involved in the hydrolysis of mannosidic linkages in N-linked oligosaccharides. 36866557 11 33 theme mannose 1641:1647 arg1 units 1649:1653 7-9 mannose units 1637:1653 7-9 mannose units 1637:1653 A significant decrease in the levels of oligosaccharides with 7-9 mannose units was detected by HPLC. 36866557 6 34 theme laser 895:899 arg1 MALDI-TOF/TOF 954:966 MALDI-TOF/TOF 954:966 MALDI-TOF/TOF 954:966 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 6 34 theme laser 895:899 arg1 spectrometry 974:985 matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry 879:985 matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry 879:985 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 1 35 theme BACKGROUND 97:106 arg1 Alpha-mannosidosis 108:125 BACKGROUND Alpha-mannosidosis 97:125 BACKGROUND Alpha-mannosidosis 97:125 BACKGROUND Alpha-mannosidosis is a rare lysosomal storage disorder, caused by decreased activity of α-D-mannosidase. 36866557 1 35 theme BACKGROUND 97:106 arg1 disorder 155:162 a rare lysosomal storage disorder 130:162 a rare lysosomal storage disorder 130:162 BACKGROUND Alpha-mannosidosis is a rare lysosomal storage disorder, caused by decreased activity of α-D-mannosidase. 36866557 12 36 theme oligosaccharide 1751:1765 arg1 biomarkers 1767:1776 oligosaccharide biomarkers 1751:1776 oligosaccharide biomarkers 1751:1776 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 5 37 theme fluorescence 810:821 arg1 detector 823:830 fluorescence detector 810:830 fluorescence detector (FLD) 810:836 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 5 37 theme fluorescence 810:821 arg1 FLD 833:835 FLD 833:835 FLD 833:835 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 4 38 theme urinary 522:528 arg1 oligosaccharides 543:558 urinary mannose-rich oligosaccharides 522:558 urinary mannose-rich oligosaccharides 522:558 METHODS In this work, we determined the levels of urinary mannose-rich oligosaccharides in a patient subjected to novel enzyme replacement therapy. 36866557 12 39 from application 1693:1703 arg1 quantification 1733:1746 quantification 1733:1746 quantification of oligosaccharide biomarkers 1733:1776 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 4 40 theme oligosaccharides 543:558 arg1 levels 512:517 the levels 508:517 the levels of urinary mannose-rich oligosaccharides in a patient subjected to novel enzyme replacement therapy 508:617 METHODS In this work, we determined the levels of urinary mannose-rich oligosaccharides in a patient subjected to novel enzyme replacement therapy. 36866557 10 41 from decrease 1471:1478 arg1 oligosaccharides 1510:1525 total urinary mannose-rich oligosaccharides 1483:1525 total urinary mannose-rich oligosaccharides 1483:1525 After four months, an approximately ten-folds significant decrease in total urinary mannose-rich oligosaccharides was detected, suggesting therapy effectiveness. 36866557 6 42 theme mass 969:972 arg1 MALDI-TOF/TOF 954:966 MALDI-TOF/TOF 954:966 MALDI-TOF/TOF 954:966 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 6 42 theme mass 969:972 arg1 spectrometry 974:985 matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry 879:985 matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry 879:985 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 4 43 theme novel 586:590 arg1 therapy 611:617 novel enzyme replacement therapy 586:617 novel enzyme replacement therapy 586:617 METHODS In this work, we determined the levels of urinary mannose-rich oligosaccharides in a patient subjected to novel enzyme replacement therapy. 36866557 12 44 dep CONCLUSIONS 1677:1687 arg1 application 1693:1703 The application 1689:1703 The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers 1689:1776 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 12 44 dep CONCLUSIONS 1677:1687 arg1 approach 1792:1799 a suitable approach 1781:1799 a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients 1781:1865 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 4 45 theme replacement 599:609 arg1 therapy 611:617 novel enzyme replacement therapy 586:617 novel enzyme replacement therapy 586:617 METHODS In this work, we determined the levels of urinary mannose-rich oligosaccharides in a patient subjected to novel enzyme replacement therapy. 36866557 10 46 theme ten-folds 1449:1457 arg1 decrease 1471:1478 an approximately ten-folds significant decrease 1432:1478 an approximately ten-folds significant decrease in total urinary mannose-rich oligosaccharides 1432:1525 After four months, an approximately ten-folds significant decrease in total urinary mannose-rich oligosaccharides was detected, suggesting therapy effectiveness. 36866557 9 47 from decrease 1306:1313 arg1 oligosaccharides 1337:1352 total mannose-rich oligosaccharides 1318:1352 total mannose-rich oligosaccharides 1318:1352 RESULTS Compared to levels before the administration of therapy, an approximately two-folds decrease in total mannose-rich oligosaccharides after one month of treatment was observed by NMR and HPLC. 36866557 6 48 theme time-of-flight/time-of-flight 923:951 arg1 MALDI-TOF/TOF 954:966 MALDI-TOF/TOF 954:966 MALDI-TOF/TOF 954:966 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 6 48 theme time-of-flight/time-of-flight 923:951 arg1 spectrometry 974:985 matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry 879:985 matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry 879:985 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 5 49 theme solid 666:670 arg1 SPE 690:692 SPE 690:692 SPE 690:692 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 5 49 theme solid 666:670 arg1 extraction 678:687 solid phase extraction 666:687 solid phase extraction (SPE) 666:693 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 10 50 theme mannose-rich 1497:1508 arg1 oligosaccharides 1510:1525 total urinary mannose-rich oligosaccharides 1483:1525 total urinary mannose-rich oligosaccharides 1483:1525 After four months, an approximately ten-folds significant decrease in total urinary mannose-rich oligosaccharides was detected, suggesting therapy effectiveness. 36866557 8 51 theme paired 1167:1172 arg1 t-test 1174:1179 one-tailed paired t-test 1156:1179 one-tailed paired t-test 1156:1179 The data were analyzed using one-tailed paired t-test and Pearson's correlation tests. 36866557 1 52 theme decreased 175:183 arg1 activity 185:192 decreased activity 175:192 decreased activity of α-D-mannosidase 175:211 BACKGROUND Alpha-mannosidosis is a rare lysosomal storage disorder, caused by decreased activity of α-D-mannosidase. 36866557 11 53 with oligosaccharides 1615:1630 arg1 units 1649:1653 7-9 mannose units 1637:1653 7-9 mannose units 1637:1653 A significant decrease in the levels of oligosaccharides with 7-9 mannose units was detected by HPLC. 36866557 12 54 theme HPLC-FLD 1713:1720 arg1 application 1693:1703 The application 1689:1703 The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers 1689:1776 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 12 54 theme HPLC-FLD 1713:1720 arg1 approach 1792:1799 a suitable approach 1781:1799 a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients 1781:1865 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 5 55 theme tag 719:721 arg1 2-aminobenzamide 723:738 fluorescent tag 2-aminobenzamide 707:738 fluorescent tag 2-aminobenzamide 707:738 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 10 56 theme total 1483:1487 arg1 oligosaccharides 1510:1525 total urinary mannose-rich oligosaccharides 1483:1525 total urinary mannose-rich oligosaccharides 1483:1525 After four months, an approximately ten-folds significant decrease in total urinary mannose-rich oligosaccharides was detected, suggesting therapy effectiveness. 36866557 12 57 theme NMR 1726:1728 arg1 application 1693:1703 The application 1689:1703 The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers 1689:1776 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 12 57 theme NMR 1726:1728 arg1 approach 1792:1799 a suitable approach 1781:1799 a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients 1781:1865 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 2 58 link N-linked 282:289 arg1 oligosaccharides 291:306 N-linked oligosaccharides 282:306 N-linked oligosaccharides 282:306 This enzyme is involved in the hydrolysis of mannosidic linkages in N-linked oligosaccharides. 36866557 9 59 theme total 1318:1322 arg1 oligosaccharides 1337:1352 total mannose-rich oligosaccharides 1318:1352 total mannose-rich oligosaccharides 1318:1352 RESULTS Compared to levels before the administration of therapy, an approximately two-folds decrease in total mannose-rich oligosaccharides after one month of treatment was observed by NMR and HPLC. 36866557 7 60 theme magnetic 1088:1095 arg1 NMR 1108:1110 NMR 1108:1110 NMR 1108:1110 In addition, the levels of urinary mannose-rich oligosaccharides were also quantified by 1H nuclear magnetic resonance (NMR) spectroscopy. 36866557 7 60 theme magnetic 1088:1095 arg1 resonance 1097:1105 1H nuclear magnetic resonance 1077:1105 1H nuclear magnetic resonance (NMR) spectroscopy 1077:1124 In addition, the levels of urinary mannose-rich oligosaccharides were also quantified by 1H nuclear magnetic resonance (NMR) spectroscopy. 36866557 7 61 theme resonance 1097:1105 arg1 spectroscopy 1113:1124 1H nuclear magnetic resonance (NMR) spectroscopy 1077:1124 1H nuclear magnetic resonance (NMR) spectroscopy 1077:1124 In addition, the levels of urinary mannose-rich oligosaccharides were also quantified by 1H nuclear magnetic resonance (NMR) spectroscopy. 36866557 2 62 theme mannosidic 259:268 arg1 linkages 270:277 mannosidic linkages 259:277 mannosidic linkages 259:277 This enzyme is involved in the hydrolysis of mannosidic linkages in N-linked oligosaccharides. 36866557 5 63 theme Urinary 620:626 arg1 oligosaccharides 628:643 Urinary oligosaccharides 620:643 Urinary oligosaccharides 620:643 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 12 64 theme therapy 1819:1825 arg1 efficacy 1827:1834 therapy efficacy 1819:1834 therapy efficacy 1819:1834 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 12 65 from monitoring 1805:1814 arg1 patients 1858:1865 alpha-mannosidosis patients 1839:1865 alpha-mannosidosis patients 1839:1865 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 11 66 theme significant 1577:1587 arg1 decrease 1589:1596 A significant decrease 1575:1596 A significant decrease in the levels of oligosaccharides with 7-9 mannose units 1575:1653 A significant decrease in the levels of oligosaccharides with 7-9 mannose units was detected by HPLC. 36866557 1 67 theme lysosomal 137:145 arg1 Alpha-mannosidosis 108:125 BACKGROUND Alpha-mannosidosis 97:125 BACKGROUND Alpha-mannosidosis 97:125 BACKGROUND Alpha-mannosidosis is a rare lysosomal storage disorder, caused by decreased activity of α-D-mannosidase. 36866557 1 67 theme lysosomal 137:145 arg1 disorder 155:162 a rare lysosomal storage disorder 130:162 a rare lysosomal storage disorder 130:162 BACKGROUND Alpha-mannosidosis is a rare lysosomal storage disorder, caused by decreased activity of α-D-mannosidase. 36866557 3 68 theme undigested 340:349 arg1 oligosaccharides 364:379 undigested mannose-rich oligosaccharides 340:379 undigested mannose-rich oligosaccharides (Man2GlcNAc - Man9GlcNAc) accumulating in cells 340:427 Due to the mannosidase defect, undigested mannose-rich oligosaccharides (Man2GlcNAc - Man9GlcNAc) accumulating in cells are excreted in large quantities in urine. 36866557 11 69 theme oligosaccharides 1615:1630 arg1 levels 1605:1610 the levels 1601:1610 the levels of oligosaccharides with 7-9 mannose units 1601:1653 A significant decrease in the levels of oligosaccharides with 7-9 mannose units was detected by HPLC. 36866557 0 70 theme Efficacy 65:72 arg1 Monitoring 43:52 the Monitoring 39:52 the Monitoring of Therapy Efficacy in Alpha-Mannosidosis 39:94 The Application of HPLC-FLD and NMR in the Monitoring of Therapy Efficacy in Alpha-Mannosidosis. 36866557 0 71 from Application 4:14 arg1 Monitoring 43:52 the Monitoring 39:52 the Monitoring of Therapy Efficacy in Alpha-Mannosidosis 39:94 The Application of HPLC-FLD and NMR in the Monitoring of Therapy Efficacy in Alpha-Mannosidosis. 36866557 7 72 theme mannose-rich 1023:1034 arg1 oligosaccharides 1036:1051 urinary mannose-rich oligosaccharides 1015:1051 urinary mannose-rich oligosaccharides 1015:1051 In addition, the levels of urinary mannose-rich oligosaccharides were also quantified by 1H nuclear magnetic resonance (NMR) spectroscopy. 36866557 5 73 theme high-performance 759:774 arg1 HPLC 799:802 HPLC 799:802 HPLC 799:802 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 5 73 theme high-performance 759:774 arg1 chromatography 783:796 high-performance liquid chromatography 759:796 high-performance liquid chromatography (HPLC) with fluorescence detector (FLD) 759:836 Urinary oligosaccharides were extracted using solid phase extraction (SPE), labeled by fluorescent tag 2-aminobenzamide, and quantified by high-performance liquid chromatography (HPLC) with fluorescence detector (FLD). 36866557 12 74 theme biomarkers 1767:1776 arg1 quantification 1733:1746 quantification 1733:1746 quantification of oligosaccharide biomarkers 1733:1776 CONCLUSIONS The application of both HPLC-FLD and NMR in quantification of oligosaccharide biomarkers is a suitable approach for monitoring of therapy efficacy in alpha-mannosidosis patients. 36866557 10 75 theme therapy 1552:1558 arg1 effectiveness 1560:1572 therapy effectiveness 1552:1572 therapy effectiveness 1552:1572 After four months, an approximately ten-folds significant decrease in total urinary mannose-rich oligosaccharides was detected, suggesting therapy effectiveness. 36866557 3 76 theme large 445:449 arg1 quantities 451:460 large quantities 445:460 large quantities in urine 445:469 Due to the mannosidase defect, undigested mannose-rich oligosaccharides (Man2GlcNAc - Man9GlcNAc) accumulating in cells are excreted in large quantities in urine. 36866557 0 77 theme HPLC-FLD 19:26 arg1 Application 4:14 The Application 0:14 The Application of HPLC-FLD and NMR in the Monitoring of Therapy Efficacy in Alpha-Mannosidosis. 0:95 The Application of HPLC-FLD and NMR in the Monitoring of Therapy Efficacy in Alpha-Mannosidosis. 36866557 0 78 theme NMR 32:34 arg1 Application 4:14 The Application 0:14 The Application of HPLC-FLD and NMR in the Monitoring of Therapy Efficacy in Alpha-Mannosidosis. 0:95 The Application of HPLC-FLD and NMR in the Monitoring of Therapy Efficacy in Alpha-Mannosidosis. 36866557 8 79 theme one-tailed 1156:1165 arg1 t-test 1174:1179 one-tailed paired t-test 1156:1179 one-tailed paired t-test 1156:1179 The data were analyzed using one-tailed paired t-test and Pearson's correlation tests. 36866557 6 80 theme matrix-assisted 879:893 arg1 MALDI-TOF/TOF 954:966 MALDI-TOF/TOF 954:966 MALDI-TOF/TOF 954:966 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 6 80 theme matrix-assisted 879:893 arg1 spectrometry 974:985 matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry 879:985 matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry 879:985 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 4 81 theme mannose-rich 530:541 arg1 oligosaccharides 543:558 urinary mannose-rich oligosaccharides 522:558 urinary mannose-rich oligosaccharides 522:558 METHODS In this work, we determined the levels of urinary mannose-rich oligosaccharides in a patient subjected to novel enzyme replacement therapy. 36866557 3 82 dep oligosaccharides 364:379 arg1 Man9GlcNAc 395:404 Man9GlcNAc 395:404 Man9GlcNAc 395:404 Due to the mannosidase defect, undigested mannose-rich oligosaccharides (Man2GlcNAc - Man9GlcNAc) accumulating in cells are excreted in large quantities in urine. 36866557 3 82 dep oligosaccharides 364:379 arg1 Man2GlcNAc 382:391 Man2GlcNAc 382:391 Man2GlcNAc 382:391 Due to the mannosidase defect, undigested mannose-rich oligosaccharides (Man2GlcNAc - Man9GlcNAc) accumulating in cells are excreted in large quantities in urine. 36866557 6 83 theme peaks 855:859 arg1 identity 843:850 The identity 839:850 The identity of peaks 839:859 The identity of peaks was determined by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. 36866557 8 84 theme correlation 1195:1205 arg1 tests 1207:1211 Pearson's correlation tests 1185:1211 Pearson's correlation tests 1185:1211 The data were analyzed using one-tailed paired t-test and Pearson's correlation tests. 36866557 3 85 from quantities 451:460 arg1 urine 465:469 urine 465:469 urine 465:469 Due to the mannosidase defect, undigested mannose-rich oligosaccharides (Man2GlcNAc - Man9GlcNAc) accumulating in cells are excreted in large quantities in urine. 36737977 0 0 theme plant-based 81:91 arg1 meat 93:96 plant-based meat 81:96 plant-based meat 81:96 Improving the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat by eliminating N-glycosylation. 36737977 5 1 link N-linked 930:937 arg1 oligosaccharides 939:954 the complex N-linked oligosaccharides 918:954 the complex N-linked oligosaccharides 918:954 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 6 2 theme smoother 1063:1070 arg1 surface 1084:1090 a smoother and flatter surface 1061:1090 a smoother and flatter surface of the high-moisture protein extrudate matrix 1061:1136 In addition, rAFP pretreatment resulted in a smoother and flatter surface of the high-moisture protein extrudate matrix compared to the commercial cryoprotectant trehalose. 36737977 6 3 theme commercial 1154:1163 arg1 trehalose 1180:1188 the commercial cryoprotectant trehalose 1150:1188 the commercial cryoprotectant trehalose 1150:1188 In addition, rAFP pretreatment resulted in a smoother and flatter surface of the high-moisture protein extrudate matrix compared to the commercial cryoprotectant trehalose. 36737977 7 4 theme effective 1248:1256 arg1 cryoprotectant 1258:1271 a new effective cryoprotectant 1242:1271 a new effective cryoprotectant in meat alternatives 1242:1292 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 7 4 theme effective 1248:1256 arg1 applications 1226:1237 potential applications 1216:1237 potential applications 1216:1237 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 7 5 from cryoprotectant 1258:1271 arg1 alternatives 1281:1292 meat alternatives 1276:1292 meat alternatives 1276:1292 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 3 6 theme Daucus 467:472 arg1 DcAFP 501:505 DcAFP 501:505 DcAFP 501:505 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 3 6 theme Daucus 467:472 arg1 protein 492:498 Daucus carota antifreeze protein 467:498 Daucus carota antifreeze protein (DcAFP) 467:506 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 5 7 dep viscoelasticity 825:839 arg1 features 864:871 features 864:871 features 864:871 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 5 8 theme rAFPs 994:998 arg1 binding 983:989 the binding 979:989 the binding of rAFPs to ice molecules 979:1015 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 3 9 theme carota 474:479 arg1 DcAFP 501:505 DcAFP 501:505 DcAFP 501:505 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 3 9 theme carota 474:479 arg1 protein 492:498 Daucus carota antifreeze protein 467:498 Daucus carota antifreeze protein (DcAFP) 467:506 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 6 10 theme rAFP 1031:1034 arg1 pretreatment 1036:1047 rAFP pretreatment 1031:1047 rAFP pretreatment 1031:1047 In addition, rAFP pretreatment resulted in a smoother and flatter surface of the high-moisture protein extrudate matrix compared to the commercial cryoprotectant trehalose. 36737977 1 11 theme freeze-thaw 245:255 arg1 cycles 257:262 freeze-thaw cycles 245:262 freeze-thaw cycles in commercial transportation and household storage 245:313 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 5 12 theme N-linked 930:937 arg1 oligosaccharides 939:954 the complex N-linked oligosaccharides 918:954 the complex N-linked oligosaccharides 918:954 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 1 13 from storage 307:313 arg1 result 235:240 a result 233:240 a result of freeze-thaw cycles in commercial transportation and household storage 233:313 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 1 14 theme cycles 257:262 arg1 result 235:240 a result 233:240 a result of freeze-thaw cycles in commercial transportation and household storage 233:313 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 7 15 theme meat 1276:1279 arg1 alternatives 1281:1292 meat alternatives 1276:1292 meat alternatives 1276:1292 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 1 16 from transportation 278:291 arg1 result 235:240 a result 233:240 a result of freeze-thaw cycles in commercial transportation and household storage 233:313 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 3 17 dep Komagataella 583:594 arg1 phaffii 596:602 phaffii 596:602 phaffii 596:602 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 6 18 dep resulted 1049:1056 arg1 compared 1138:1145 compared 1138:1145 compared to the commercial cryoprotectant trehalose 1138:1188 In addition, rAFP pretreatment resulted in a smoother and flatter surface of the high-moisture protein extrudate matrix compared to the commercial cryoprotectant trehalose. 36737977 1 19 theme plant-based 166:176 arg1 PBM 184:186 PBM 184:186 PBM 184:186 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 1 19 theme plant-based 166:176 arg1 meat 178:181 plant-based meat 166:181 plant-based meat (PBM) 166:187 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 5 20 theme rDcAFP-treated 889:902 arg1 group 904:908 the rDcAFP-treated group 885:908 the rDcAFP-treated group 885:908 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 2 21 theme cycles 444:449 arg1 result 416:421 a result 414:421 a result of these freeze-thaw cycles 414:449 There is a need to reduce the deterioration of PBM attributes, such as water holding capacity, as a result of these freeze-thaw cycles. 36737977 2 21 theme cycles 444:449 arg1 deterioration 346:358 the deterioration 342:358 the deterioration of PBM attributes, such as water holding capacity 342:408 There is a need to reduce the deterioration of PBM attributes, such as water holding capacity, as a result of these freeze-thaw cycles. 36737977 4 22 theme water 734:738 arg1 distribution 740:751 water distribution 734:751 water distribution 734:751 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 6 23 theme flatter 1076:1082 arg1 surface 1084:1090 a smoother and flatter surface 1061:1090 a smoother and flatter surface of the high-moisture protein extrudate matrix 1061:1136 In addition, rAFP pretreatment resulted in a smoother and flatter surface of the high-moisture protein extrudate matrix compared to the commercial cryoprotectant trehalose. 36737977 4 24 theme pretreatment 624:635 arg1 effects 613:619 The effects 609:619 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM 609:758 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 3 25 theme antifreeze 481:490 arg1 DcAFP 501:505 DcAFP 501:505 DcAFP 501:505 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 3 25 theme antifreeze 481:490 arg1 protein 492:498 Daucus carota antifreeze protein 467:498 Daucus carota antifreeze protein (DcAFP) 467:506 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 3 26 theme deglycosylated 516:529 arg1 DcAFP-N294G 538:548 its deglycosylated mutant DcAFP-N294G 512:548 its deglycosylated mutant DcAFP-N294G 512:548 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 2 27 theme attributes 367:376 arg1 result 416:421 a result 414:421 a result of these freeze-thaw cycles 414:449 There is a need to reduce the deterioration of PBM attributes, such as water holding capacity, as a result of these freeze-thaw cycles. 36737977 2 27 theme attributes 367:376 arg1 deterioration 346:358 the deterioration 342:358 the deterioration of PBM attributes, such as water holding capacity 342:408 There is a need to reduce the deterioration of PBM attributes, such as water holding capacity, as a result of these freeze-thaw cycles. 36737977 7 28 theme Deglycosylated 1191:1204 arg1 DcAFP 1206:1210 Deglycosylated DcAFP 1191:1210 Deglycosylated DcAFP 1191:1210 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 5 29 contain had 812:814 arg1 samples 804:810 The rDcAFP-N294G-treated PBM samples 775:810 The rDcAFP-N294G-treated PBM samples 775:810 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 5 29 contain had 812:814 arg2 distribution 851:862 water distribution 845:862 water distribution 845:862 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 5 29 contain had 812:814 arg2 viscoelasticity 825:839 superior viscoelasticity 816:839 superior viscoelasticity 816:839 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 3 30 theme mutant 531:536 arg1 DcAFP-N294G 538:548 its deglycosylated mutant DcAFP-N294G 512:548 its deglycosylated mutant DcAFP-N294G 512:548 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 2 31 theme PBM 363:365 arg1 attributes 367:376 PBM attributes 363:376 PBM attributes 363:376 There is a need to reduce the deterioration of PBM attributes, such as water holding capacity, as a result of these freeze-thaw cycles. 36737977 2 31 theme PBM 363:365 arg1 capacity 401:408 water holding capacity 387:408 water holding capacity 387:408 There is a need to reduce the deterioration of PBM attributes, such as water holding capacity, as a result of these freeze-thaw cycles. 36737977 5 32 theme rDcAFP-N294G-treated 779:798 arg1 samples 804:810 The rDcAFP-N294G-treated PBM samples 775:810 The rDcAFP-N294G-treated PBM samples 775:810 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 1 33 theme commercial 267:276 arg1 transportation 278:291 commercial transportation 267:291 commercial transportation 267:291 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 5 34 theme complex 922:928 arg1 oligosaccharides 939:954 the complex N-linked oligosaccharides 918:954 the complex N-linked oligosaccharides 918:954 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 4 35 dep microstructure 674:687 arg1 the 670:672 the 670:672 the 670:672 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 4 36 from effects 613:619 arg1 microstructure 674:687 microstructure 674:687 microstructure 674:687 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 4 36 from effects 613:619 arg1 properties 702:711 rheological properties 690:711 rheological properties 690:711 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 4 36 from effects 613:619 arg1 mobility 720:727 water mobility 714:727 water mobility 714:727 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 4 36 from effects 613:619 arg1 distribution 740:751 water distribution 734:751 water distribution 734:751 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 0 37 theme cryoprotective 14:27 arg1 effect 29:34 the cryoprotective effect 10:34 the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat 10:96 Improving the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat by eliminating N-glycosylation. 36737977 1 38 from cycles 257:262 arg1 transportation 278:291 commercial transportation 267:291 commercial transportation 267:291 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 1 38 from cycles 257:262 arg1 storage 307:313 household storage 297:313 household storage 297:313 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 4 39 theme water 714:718 arg1 mobility 720:727 water mobility 714:727 water mobility 714:727 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 2 40 theme holding 393:399 arg1 capacity 401:408 water holding capacity 387:408 water holding capacity 387:408 There is a need to reduce the deterioration of PBM attributes, such as water holding capacity, as a result of these freeze-thaw cycles. 36737977 0 41 theme antifreeze 39:48 arg1 proteins 50:57 antifreeze proteins 39:57 antifreeze proteins from Daucus carota 39:76 Improving the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat by eliminating N-glycosylation. 36737977 6 42 theme extrudate 1121:1129 arg1 matrix 1131:1136 the high-moisture protein extrudate matrix 1095:1136 the high-moisture protein extrudate matrix 1095:1136 In addition, rAFP pretreatment resulted in a smoother and flatter surface of the high-moisture protein extrudate matrix compared to the commercial cryoprotectant trehalose. 36737977 1 43 from result 235:240 arg1 transportation 278:291 commercial transportation 267:291 commercial transportation 267:291 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 1 43 from result 235:240 arg1 storage 307:313 household storage 297:313 household storage 297:313 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 5 44 theme superior 816:823 arg1 viscoelasticity 825:839 superior viscoelasticity 816:839 superior viscoelasticity 816:839 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 4 45 theme recombinant 642:652 arg1 rAFPs 660:664 rAFPs 660:664 rAFPs 660:664 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 4 45 theme recombinant 642:652 arg1 AFPs 654:657 recombinant AFPs 642:657 recombinant AFPs (rAFPs) 642:665 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 2 46 theme water 387:391 arg1 capacity 401:408 water holding capacity 387:408 water holding capacity 387:408 There is a need to reduce the deterioration of PBM attributes, such as water holding capacity, as a result of these freeze-thaw cycles. 36737977 2 47 theme freeze-thaw 432:442 arg1 cycles 444:449 these freeze-thaw cycles 426:449 these freeze-thaw cycles 426:449 There is a need to reduce the deterioration of PBM attributes, such as water holding capacity, as a result of these freeze-thaw cycles. 36737977 1 48 theme household 297:305 arg1 storage 307:313 household storage 297:313 household storage 297:313 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 0 49 from carota 71:76 arg1 effect 29:34 the cryoprotective effect 10:34 the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat 10:96 Improving the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat by eliminating N-glycosylation. 36737977 0 49 from carota 71:76 arg1 proteins 50:57 antifreeze proteins 39:57 antifreeze proteins from Daucus carota 39:76 Improving the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat by eliminating N-glycosylation. 36737977 7 50 contain has 1212:1214 arg2 cryoprotectant 1258:1271 a new effective cryoprotectant 1242:1271 a new effective cryoprotectant in meat alternatives 1242:1292 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 7 50 contain has 1212:1214 arg1 DcAFP 1206:1210 Deglycosylated DcAFP 1191:1210 Deglycosylated DcAFP 1191:1210 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 7 50 contain has 1212:1214 arg2 applications 1226:1237 potential applications 1216:1237 potential applications 1216:1237 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 7 51 theme potential 1216:1224 arg1 cryoprotectant 1258:1271 a new effective cryoprotectant 1242:1271 a new effective cryoprotectant in meat alternatives 1242:1292 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 7 51 theme potential 1216:1224 arg1 applications 1226:1237 potential applications 1216:1237 potential applications 1216:1237 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 4 52 with pretreatment 624:635 arg1 rAFPs 660:664 rAFPs 660:664 rAFPs 660:664 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 4 52 with pretreatment 624:635 arg1 AFPs 654:657 recombinant AFPs 642:657 recombinant AFPs (rAFPs) 642:665 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 6 53 theme matrix 1131:1136 arg1 surface 1084:1090 a smoother and flatter surface 1061:1090 a smoother and flatter surface of the high-moisture protein extrudate matrix 1061:1136 In addition, rAFP pretreatment resulted in a smoother and flatter surface of the high-moisture protein extrudate matrix compared to the commercial cryoprotectant trehalose. 36737977 0 54 theme proteins 50:57 arg1 effect 29:34 the cryoprotective effect 10:34 the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat 10:96 Improving the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat by eliminating N-glycosylation. 36737977 3 55 gly deglycosylated 516:529 arg1 DcAFP-N294G 538:548 its deglycosylated mutant DcAFP-N294G 512:548 its deglycosylated mutant DcAFP-N294G 512:548 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 5 56 theme ice 1003:1005 arg1 molecules 1007:1015 ice molecules 1003:1015 ice molecules 1003:1015 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 7 57 gly Deglycosylated 1191:1204 arg1 DcAFP 1206:1210 Deglycosylated DcAFP 1191:1210 Deglycosylated DcAFP 1191:1210 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 4 58 theme PBM 756:758 arg1 microstructure 674:687 microstructure 674:687 microstructure 674:687 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 4 58 theme PBM 756:758 arg1 properties 702:711 rheological properties 690:711 rheological properties 690:711 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 4 58 theme PBM 756:758 arg1 mobility 720:727 water mobility 714:727 water mobility 714:727 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 4 58 theme PBM 756:758 arg1 distribution 740:751 water distribution 734:751 water distribution 734:751 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 4 59 theme rheological 690:700 arg1 properties 702:711 rheological properties 690:711 rheological properties 690:711 The effects of pretreatment with recombinant AFPs (rAFPs) on the microstructure, rheological properties, water mobility, and water distribution of PBM were assessed. 36737977 6 60 theme high-moisture 1099:1111 arg1 matrix 1131:1136 the high-moisture protein extrudate matrix 1095:1136 the high-moisture protein extrudate matrix 1095:1136 In addition, rAFP pretreatment resulted in a smoother and flatter surface of the high-moisture protein extrudate matrix compared to the commercial cryoprotectant trehalose. 36737977 1 61 theme quality 213:219 arg1 problems 221:228 quality problems 213:228 quality problems 213:228 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 6 62 theme cryoprotectant 1165:1178 arg1 trehalose 1180:1188 the commercial cryoprotectant trehalose 1150:1188 the commercial cryoprotectant trehalose 1150:1188 In addition, rAFP pretreatment resulted in a smoother and flatter surface of the high-moisture protein extrudate matrix compared to the commercial cryoprotectant trehalose. 36737977 5 63 theme PBM 800:802 arg1 samples 804:810 The rDcAFP-N294G-treated PBM samples 775:810 The rDcAFP-N294G-treated PBM samples 775:810 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 1 64 theme novel 135:139 arg1 alternative 153:163 a novel animal meat alternative 133:163 a novel animal meat alternative 133:163 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 6 65 theme protein 1113:1119 arg1 matrix 1131:1136 the high-moisture protein extrudate matrix 1095:1136 the high-moisture protein extrudate matrix 1095:1136 In addition, rAFP pretreatment resulted in a smoother and flatter surface of the high-moisture protein extrudate matrix compared to the commercial cryoprotectant trehalose. 36737977 7 66 theme new 1244:1246 arg1 cryoprotectant 1258:1271 a new effective cryoprotectant 1242:1271 a new effective cryoprotectant in meat alternatives 1242:1292 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 7 66 theme new 1244:1246 arg1 applications 1226:1237 potential applications 1216:1237 potential applications 1216:1237 Deglycosylated DcAFP has potential applications as a new effective cryoprotectant in meat alternatives. 36737977 1 67 theme animal 141:146 arg1 alternative 153:163 a novel animal meat alternative 133:163 a novel animal meat alternative 133:163 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 36737977 5 68 theme water 845:849 arg1 distribution 851:862 water distribution 845:862 water distribution 845:862 The rDcAFP-N294G-treated PBM samples had superior viscoelasticity and water distribution features compared to the rDcAFP-treated group because the complex N-linked oligosaccharides did not interfere with the binding of rAFPs to ice molecules. 36737977 0 69 theme Daucus 64:69 arg1 carota 71:76 Daucus carota 64:76 Daucus carota 64:76 Improving the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat by eliminating N-glycosylation. 36737977 0 70 from effect 29:34 arg1 carota 71:76 Daucus carota 64:76 Daucus carota 64:76 Improving the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat by eliminating N-glycosylation. 36737977 0 70 from effect 29:34 arg1 meat 93:96 plant-based meat 81:96 plant-based meat 81:96 Improving the cryoprotective effect of antifreeze proteins from Daucus carota on plant-based meat by eliminating N-glycosylation. 36737977 3 71 theme Komagataella 583:594 arg1 X33 604:606 Komagataella phaffii X33 583:606 Komagataella phaffii X33 583:606 In this study, Daucus carota antifreeze protein (DcAFP) and its deglycosylated mutant DcAFP-N294G were heterologously expressed in Komagataella phaffii X33. 36737977 1 72 theme meat 148:151 arg1 alternative 153:163 a novel animal meat alternative 133:163 a novel animal meat alternative 133:163 As a novel animal meat alternative, plant-based meat (PBM) frequently suffers from quality problems as a result of freeze-thaw cycles in commercial transportation and household storage. 37231419 12 0 theme CSC 2039:2041 arg1 expansion 2043:2051 glucose-driven CSC expansion 2024:2051 glucose-driven CSC expansion via TET1-O-GlcNAc 2024:2069 Suppression of pathway proteins by inhibition, RNA silencing, and overexpression confirmed a mechanism for glucose-driven CSC expansion via TET1-O-GlcNAc. 37231419 10 1 dep RESULTS 1684:1690 arg1 showed 1695:1700 showed 1695:1700 showed that OGT levels were higher in TNBC cell lines compared to non-tumor breast cells, matching patient data 1695:1805 RESULTS We showed that OGT levels were higher in TNBC cell lines compared to non-tumor breast cells, matching patient data. 37231419 10 2 theme TNBC 1733:1736 arg1 lines 1743:1747 TNBC cell lines 1733:1747 TNBC cell lines compared to non-tumor breast cells 1733:1782 RESULTS We showed that OGT levels were higher in TNBC cell lines compared to non-tumor breast cells, matching patient data. 37231419 17 3 theme metabolic 2764:2772 arg1 diseases 2774:2781 metabolic diseases 2764:2781 metabolic diseases 2764:2781 Because pre-menopausal TNBC risk and mortality are correlated with metabolic diseases, our results could lead to new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression. 37231419 11 4 theme protein 1876:1882 arg1 TET1 1884:1887 the protein TET1 1872:1887 the protein TET1 1872:1887 Our data identified that hyperglycemia drove O-GlcNAcylation of the protein TET1 via OGT-catalyzed activity. 37231419 7 5 theme novel 1090:1094 arg1 link 1165:1168 a potential molecular link 1143:1168 a potential molecular link between hyperglycemic conditions and CSC tumor risk factors 1143:1228 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 7 5 theme novel 1090:1094 arg1 pathway 1096:1102 a novel pathway 1088:1102 a novel pathway for glucose-driven expansion of CSC 1088:1138 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 1 6 theme tumors 175:180 arg1 metabolism 143:152 BACKGROUND Enhanced glucose metabolism 115:152 BACKGROUND Enhanced glucose metabolism 115:152 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 1 6 theme tumors 175:180 arg1 feature 159:165 a feature 157:165 a feature of most tumors 157:180 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 12 7 theme RNA 1964:1966 arg1 silencing 1968:1976 RNA silencing 1964:1976 RNA silencing 1964:1976 Suppression of pathway proteins by inhibition, RNA silencing, and overexpression confirmed a mechanism for glucose-driven CSC expansion via TET1-O-GlcNAc. 37231419 9 8 theme model 1669:1673 arg1 systems 1675:1681 TNBC model systems 1664:1681 TNBC model systems 1664:1681 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 8 9 theme chemical 1247:1254 arg1 tools 1264:1268 chemical biology tools 1247:1268 chemical biology tools 1247:1268 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 14 10 theme pathway 2367:2373 arg1 relevance 2349:2357 relevance 2349:2357 relevance of this pathway 2349:2373 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 5 11 theme cell 904:907 arg1 expansion 915:923 cancer stem-like cell (CSC) expansion 887:923 cancer stem-like cell (CSC) expansion 887:923 The data in this report implicate roles of OGT and O-GlcNAc within a pathway leading to cancer stem-like cell (CSC) expansion. 37231419 16 12 theme hyperglycemia-driven 2620:2639 arg1 risk 2655:2658 hyperglycemia-driven breast cancer risk 2620:2658 hyperglycemia-driven breast cancer risk 2620:2658 This pathway can be potentially targeted to reduce hyperglycemia-driven breast cancer risk, for instance in metabolic diseases. 37231419 13 13 theme higher 2118:2123 arg1 levels 2125:2130 higher levels 2118:2130 higher levels of OGT production 2118:2148 Furthermore, activation of the pathway led to higher levels of OGT production via feed-forward regulation in hyperglycemic conditions. 37231419 1 14 theme functional 198:207 arg1 effects 209:215 downstream functional effects 187:215 downstream functional effects of aberrant glucose flux 187:240 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 12 15 theme proteins 1940:1947 arg1 Suppression 1917:1927 Suppression 1917:1927 Suppression of pathway proteins by inhibition, RNA silencing, and overexpression 1917:1996 Suppression of pathway proteins by inhibition, RNA silencing, and overexpression confirmed a mechanism for glucose-driven CSC expansion via TET1-O-GlcNAc. 37231419 6 16 theme cells 963:967 arg1 CSCs 926:929 CSCs 926:929 CSCs 926:929 CSCs are the minor fraction of tumor cells recognized as a source of tumors as well as fueling metastatic recurrence. 37231419 6 16 theme cells 963:967 arg1 fraction 945:952 the minor fraction 935:952 the minor fraction of tumor cells recognized as a source of tumors as well as fueling metastatic recurrence 935:1041 CSCs are the minor fraction of tumor cells recognized as a source of tumors as well as fueling metastatic recurrence. 37231419 8 17 theme post-translational 1427:1444 arg1 modification 1446:1457 an O-GlcNAc post-translational modification 1415:1457 an O-GlcNAc post-translational modification in three TNBC cell lines 1415:1482 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 11 18 theme TET1 1884:1887 arg1 O-GlcNAcylation 1853:1867 O-GlcNAcylation 1853:1867 O-GlcNAcylation of the protein TET1 1853:1887 Our data identified that hyperglycemia drove O-GlcNAcylation of the protein TET1 via OGT-catalyzed activity. 37231419 7 19 theme potential 1145:1153 arg1 link 1165:1168 a potential molecular link 1143:1168 a potential molecular link between hyperglycemic conditions and CSC tumor risk factors 1143:1228 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 7 19 theme potential 1145:1153 arg1 pathway 1096:1102 a novel pathway 1088:1102 a novel pathway for glucose-driven expansion of CSC 1088:1138 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 15 20 theme hyperglycemic 2504:2516 arg1 conditions 2518:2527 hyperglycemic conditions 2504:2527 hyperglycemic conditions 2504:2527 CONCLUSIONS Taken together, our data revealed a mechanism whereby hyperglycemic conditions activated a CSC pathway in TNBC models. 37231419 9 21 from OGT 1657:1659 arg1 systems 1675:1681 TNBC model systems 1664:1681 TNBC model systems 1664:1681 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 17 22 theme pre-menopausal 2705:2718 arg1 risk 2725:2728 pre-menopausal TNBC risk 2705:2728 pre-menopausal TNBC risk 2705:2728 Because pre-menopausal TNBC risk and mortality are correlated with metabolic diseases, our results could lead to new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression. 37231419 5 23 from data 803:806 arg1 report 816:821 this report 811:821 this report 811:821 The data in this report implicate roles of OGT and O-GlcNAc within a pathway leading to cancer stem-like cell (CSC) expansion. 37231419 10 24 theme breast 1771:1776 arg1 cells 1778:1782 non-tumor breast cells 1761:1782 non-tumor breast cells 1761:1782 RESULTS We showed that OGT levels were higher in TNBC cell lines compared to non-tumor breast cells, matching patient data. 37231419 9 25 theme biochemical 1491:1501 arg1 approaches 1503:1512 biochemical approaches 1491:1512 biochemical approaches 1491:1512 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 6 26 theme minor 939:943 arg1 CSCs 926:929 CSCs 926:929 CSCs 926:929 CSCs are the minor fraction of tumor cells recognized as a source of tumors as well as fueling metastatic recurrence. 37231419 6 26 theme minor 939:943 arg1 fraction 945:952 the minor fraction 935:952 the minor fraction of tumor cells recognized as a source of tumors as well as fueling metastatic recurrence 935:1041 CSCs are the minor fraction of tumor cells recognized as a source of tumors as well as fueling metastatic recurrence. 37231419 8 27 theme TNBC 1468:1471 arg1 lines 1478:1482 three TNBC cell lines 1462:1482 three TNBC cell lines 1462:1482 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 4 28 theme O-GlcNAc 771:778 arg1 OGT 793:795 OGT 793:795 OGT 793:795 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 28 theme O-GlcNAc 771:778 arg1 transferase 780:790 O-GlcNAc transferase 771:790 O-GlcNAc transferase (OGT) 771:796 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 28 theme O-GlcNAc 771:778 arg1 enzyme 735:740 the single human enzyme 718:740 the single human enzyme that catalyzes this process 718:768 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 10 29 theme cell 1738:1741 arg1 lines 1743:1747 TNBC cell lines 1733:1747 TNBC cell lines compared to non-tumor breast cells 1733:1782 RESULTS We showed that OGT levels were higher in TNBC cell lines compared to non-tumor breast cells, matching patient data. 37231419 0 30 theme stem 63:66 arg1 pathway 73:79 a cancer stem cell pathway 54:79 a cancer stem cell pathway in triple-negative breast cancer 54:112 Hyperglycemia and O-GlcNAc transferase activity drive a cancer stem cell pathway in triple-negative breast cancer. 37231419 0 31 theme O-GlcNAc 18:25 arg1 activity 39:46 O-GlcNAc transferase activity 18:46 O-GlcNAc transferase activity 18:46 Hyperglycemia and O-GlcNAc transferase activity drive a cancer stem cell pathway in triple-negative breast cancer. 37231419 14 32 theme lean 2320:2323 arg1 littermates 2325:2335 lean littermates 2320:2335 lean littermates 2320:2335 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 7 33 theme risk 1217:1220 arg1 factors 1222:1228 CSC tumor risk factors 1207:1228 CSC tumor risk factors 1207:1228 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 9 34 theme diet-induced 1531:1542 arg1 animals 1550:1556 diet-induced obese animals 1531:1556 diet-induced obese animals 1531:1556 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 6 35 theme tumors 995:1000 arg1 source 985:990 a source 983:990 a source of tumors as well as fueling metastatic recurrence 983:1041 CSCs are the minor fraction of tumor cells recognized as a source of tumors as well as fueling metastatic recurrence. 37231419 0 36 theme triple-negative 84:98 arg1 cancer 107:112 triple-negative breast cancer 84:112 triple-negative breast cancer 84:112 Hyperglycemia and O-GlcNAc transferase activity drive a cancer stem cell pathway in triple-negative breast cancer. 37231419 17 37 theme risk 2884:2887 arg1 hyperglycemia 2865:2877 hyperglycemia 2865:2877 hyperglycemia 2865:2877 Because pre-menopausal TNBC risk and mortality are correlated with metabolic diseases, our results could lead to new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression. 37231419 17 37 theme risk 2884:2887 arg1 factor 2889:2894 a risk factor 2882:2894 a risk factor for TNBC tumorigenesis and progression 2882:2933 Because pre-menopausal TNBC risk and mortality are correlated with metabolic diseases, our results could lead to new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression. 37231419 15 38 theme CSC 2541:2543 arg1 pathway 2545:2551 a CSC pathway 2539:2551 a CSC pathway 2539:2551 CONCLUSIONS Taken together, our data revealed a mechanism whereby hyperglycemic conditions activated a CSC pathway in TNBC models. 37231419 8 39 theme regulatory 1353:1362 arg1 dioxygenase 1391:1401 the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 1333:1403 the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) 1333:1410 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 8 39 theme regulatory 1353:1362 arg1 TET1 1406:1409 TET1 1406:1409 TET1 1406:1409 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 14 40 theme O-GlcNAc 2284:2291 arg1 levels 2293:2298 elevated tumor OGT expression and O-GlcNAc levels 2250:2298 levels 2293:2298 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 2 41 theme cancer 415:420 arg1 risk 422:425 elevated pre-menopausal cancer risk 391:425 elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC) 391:466 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 5 42 theme OGT 842:844 arg1 roles 833:837 roles 833:837 roles of OGT and O-GlcNAc 833:857 The data in this report implicate roles of OGT and O-GlcNAc within a pathway leading to cancer stem-like cell (CSC) expansion. 37231419 9 43 theme biology 1572:1578 arg1 labeling 1580:1587 chemical biology labeling 1563:1587 chemical biology labeling 1563:1587 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 8 44 theme tet-methylcytosine 1372:1389 arg1 dioxygenase 1391:1401 the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 1333:1403 the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) 1333:1410 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 8 44 theme tet-methylcytosine 1372:1389 arg1 TET1 1406:1409 TET1 1406:1409 TET1 1406:1409 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 7 45 theme molecular 1155:1163 arg1 link 1165:1168 a potential molecular link 1143:1168 a potential molecular link between hyperglycemic conditions and CSC tumor risk factors 1143:1228 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 7 45 theme molecular 1155:1163 arg1 pathway 1096:1102 a novel pathway 1088:1102 a novel pathway for glucose-driven expansion of CSC 1088:1138 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 8 46 dep METHODS 1231:1237 arg1 used 1242:1245 used 1242:1245 used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines 1242:1482 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 17 47 theme new 2810:2812 arg1 directions 2814:2823 new directions 2810:2823 new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression 2810:2933 Because pre-menopausal TNBC risk and mortality are correlated with metabolic diseases, our results could lead to new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression. 37231419 17 47 theme new 2810:2812 arg1 inhibition 2839:2848 OGT inhibition 2835:2848 OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression 2835:2933 Because pre-menopausal TNBC risk and mortality are correlated with metabolic diseases, our results could lead to new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression. 37231419 4 48 theme sugar 596:600 arg1 utilization 602:612 cellular sugar utilization 587:612 cellular sugar utilization 587:612 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 14 49 theme tumor 2259:2263 arg1 expression 2269:2278 elevated tumor OGT expression and O-GlcNAc levels 2250:2298 expression 2269:2278 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 2 50 theme breast 447:452 arg1 TNBC 462:465 TNBC 462:465 TNBC 462:465 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 2 50 theme breast 447:452 arg1 cancer 454:459 triple-negative breast cancer 431:459 triple-negative breast cancer (TNBC) 431:466 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 4 51 link glucose-derived 637:651 arg1 O-GlcNAc 674:681 the glucose-derived protein modification O-GlcNAc 633:681 the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) 633:712 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 51 link glucose-derived 637:651 arg1 N-acetylglucosamine 693:711 O-linked N-acetylglucosamine 684:711 O-linked N-acetylglucosamine 684:711 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 14 52 from expression 2269:2278 arg1 mice 2303:2306 mice 2303:2306 mice 2303:2306 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 3 53 theme cancer 533:538 arg1 risk 540:543 hyperglycemic disease-coupled cancer risk 503:543 hyperglycemic disease-coupled cancer risk 503:543 However, determining pathways for hyperglycemic disease-coupled cancer risk remains a major unmet need. 37231419 7 54 theme CSC 1136:1138 arg1 expansion 1123:1131 glucose-driven expansion 1108:1131 glucose-driven expansion of CSC 1108:1138 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 16 55 from instance 2665:2672 arg1 diseases 2687:2694 metabolic diseases 2677:2694 metabolic diseases 2677:2694 This pathway can be potentially targeted to reduce hyperglycemia-driven breast cancer risk, for instance in metabolic diseases. 37231419 16 56 theme metabolic 2677:2685 arg1 diseases 2687:2694 metabolic diseases 2677:2694 metabolic diseases 2677:2694 This pathway can be potentially targeted to reduce hyperglycemia-driven breast cancer risk, for instance in metabolic diseases. 37231419 10 57 theme patient 1794:1800 arg1 data 1802:1805 patient data 1794:1805 patient data 1794:1805 RESULTS We showed that OGT levels were higher in TNBC cell lines compared to non-tumor breast cells, matching patient data. 37231419 2 58 theme hyperglycemia 343:355 arg1 component 357:365 a hyperglycemia component 341:365 a hyperglycemia component 341:365 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 1 59 theme aberrant 220:227 arg1 flux 237:240 aberrant glucose flux 220:240 aberrant glucose flux 220:240 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 9 60 theme hyperglycemia 1617:1629 arg1 impact 1607:1612 the impact 1603:1612 the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems 1603:1681 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 4 61 theme human 729:733 arg1 transferase 780:790 O-GlcNAc transferase 771:790 O-GlcNAc transferase (OGT) 771:796 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 61 theme human 729:733 arg1 enzyme 735:740 the single human enzyme 718:740 the single human enzyme that catalyzes this process 718:768 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 14 62 theme elevated 2250:2257 arg1 expression 2269:2278 elevated tumor OGT expression and O-GlcNAc levels 2250:2298 expression 2269:2278 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 3 63 theme determining 478:488 arg1 pathways 490:497 determining pathways 478:497 determining pathways for hyperglycemic disease-coupled cancer risk 478:543 However, determining pathways for hyperglycemic disease-coupled cancer risk remains a major unmet need. 37231419 8 64 theme O-GlcNAc 1418:1425 arg1 modification 1446:1457 an O-GlcNAc post-translational modification 1415:1457 an O-GlcNAc post-translational modification in three TNBC cell lines 1415:1482 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 14 65 theme microenvironment 2420:2435 arg1 model 2388:2392 an animal model 2378:2392 an animal model of the hyperglycemic TNBC microenvironment 2378:2435 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 3 66 theme major 555:559 arg1 need 567:570 a major unmet need 553:570 a major unmet need 553:570 However, determining pathways for hyperglycemic disease-coupled cancer risk remains a major unmet need. 37231419 5 67 theme cancer 887:892 arg1 CSC 910:912 CSC 910:912 CSC 910:912 The data in this report implicate roles of OGT and O-GlcNAc within a pathway leading to cancer stem-like cell (CSC) expansion. 37231419 5 67 theme cancer 887:892 arg1 cell 904:907 cancer stem-like cell 887:907 cancer stem-like cell (CSC) expansion 887:923 The data in this report implicate roles of OGT and O-GlcNAc within a pathway leading to cancer stem-like cell (CSC) expansion. 37231419 1 68 theme flux 237:240 arg1 effects 209:215 downstream functional effects 187:215 downstream functional effects of aberrant glucose flux 187:240 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 9 69 theme CSC 1634:1636 arg1 pathways 1638:1645 CSC pathways 1634:1645 CSC pathways driven by OGT in TNBC model systems 1634:1681 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 4 70 theme protein 653:659 arg1 O-GlcNAc 674:681 the glucose-derived protein modification O-GlcNAc 633:681 the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) 633:712 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 70 theme protein 653:659 arg1 N-acetylglucosamine 693:711 O-linked N-acetylglucosamine 684:711 O-linked N-acetylglucosamine 684:711 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 8 71 from modification 1446:1457 arg1 lines 1478:1482 three TNBC cell lines 1462:1482 three TNBC cell lines 1462:1482 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 7 72 theme glucose-driven 1108:1121 arg1 expansion 1123:1131 glucose-driven expansion 1108:1131 glucose-driven expansion of CSC 1108:1138 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 14 73 theme hyperglycemic 2401:2413 arg1 microenvironment 2420:2435 the hyperglycemic TNBC microenvironment 2397:2435 the hyperglycemic TNBC microenvironment 2397:2435 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 10 74 theme OGT 1707:1709 arg1 levels 1711:1716 OGT levels 1707:1716 OGT levels 1707:1716 RESULTS We showed that OGT levels were higher in TNBC cell lines compared to non-tumor breast cells, matching patient data. 37231419 13 75 theme production 2139:2148 arg1 levels 2125:2130 higher levels 2118:2130 higher levels of OGT production 2118:2148 Furthermore, activation of the pathway led to higher levels of OGT production via feed-forward regulation in hyperglycemic conditions. 37231419 12 76 theme glucose-driven 2024:2037 arg1 expansion 2043:2051 glucose-driven CSC expansion 2024:2051 glucose-driven CSC expansion via TET1-O-GlcNAc 2024:2069 Suppression of pathway proteins by inhibition, RNA silencing, and overexpression confirmed a mechanism for glucose-driven CSC expansion via TET1-O-GlcNAc. 37231419 14 77 theme diet-induced 2222:2233 arg1 obesity 2235:2241 diet-induced obesity 2222:2241 diet-induced obesity 2222:2241 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 8 78 used used 1242:1245 arg2 We 1239:1240 We 1239:1240 We 1239:1240 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 13 79 theme feed-forward 2154:2165 arg1 regulation 2167:2176 feed-forward regulation 2154:2176 feed-forward regulation in hyperglycemic conditions 2154:2204 Furthermore, activation of the pathway led to higher levels of OGT production via feed-forward regulation in hyperglycemic conditions. 37231419 14 80 theme animal 2381:2386 arg1 model 2388:2392 an animal model 2378:2392 an animal model of the hyperglycemic TNBC microenvironment 2378:2435 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 2 81 theme Metabolic 286:294 arg1 diseases 296:303 Metabolic diseases 286:303 Metabolic diseases including obesity and diabetes 286:334 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 2 81 theme Metabolic 286:294 arg1 diabetes 327:334 diabetes 327:334 diabetes 327:334 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 2 81 theme Metabolic 286:294 arg1 obesity 315:321 obesity 315:321 obesity 315:321 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 4 82 theme single 722:727 arg1 transferase 780:790 O-GlcNAc transferase 771:790 O-GlcNAc transferase (OGT) 771:796 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 82 theme single 722:727 arg1 enzyme 735:740 the single human enzyme 718:740 the single human enzyme that catalyzes this process 718:768 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 1 83 theme most 170:173 arg1 tumors 175:180 most tumors 170:180 most tumors 170:180 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 9 84 theme TNBC 1664:1667 arg1 systems 1675:1681 TNBC model systems 1664:1681 TNBC model systems 1664:1681 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 10 85 theme non-tumor 1761:1769 arg1 cells 1778:1782 non-tumor breast cells 1761:1782 non-tumor breast cells 1761:1782 RESULTS We showed that OGT levels were higher in TNBC cell lines compared to non-tumor breast cells, matching patient data. 37231419 5 86 theme stem-like 894:902 arg1 CSC 910:912 CSC 910:912 CSC 910:912 The data in this report implicate roles of OGT and O-GlcNAc within a pathway leading to cancer stem-like cell (CSC) expansion. 37231419 5 86 theme stem-like 894:902 arg1 cell 904:907 cancer stem-like cell 887:907 cancer stem-like cell (CSC) expansion 887:923 The data in this report implicate roles of OGT and O-GlcNAc within a pathway leading to cancer stem-like cell (CSC) expansion. 37231419 16 87 theme breast 2641:2646 arg1 risk 2655:2658 hyperglycemia-driven breast cancer risk 2620:2658 hyperglycemia-driven breast cancer risk 2620:2658 This pathway can be potentially targeted to reduce hyperglycemia-driven breast cancer risk, for instance in metabolic diseases. 37231419 7 88 theme study 1066:1070 arg1 objective 1048:1056 The objective 1044:1056 The objective of this study 1044:1070 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 1 89 theme downstream 187:196 arg1 effects 209:215 downstream functional effects 187:215 downstream functional effects of aberrant glucose flux 187:240 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 4 90 theme O-GlcNAc 674:681 arg1 addition 621:628 the addition 617:628 the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) 617:712 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 90 theme O-GlcNAc 674:681 arg1 aspect 577:582 One aspect 573:582 One aspect of cellular sugar utilization 573:612 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 12 91 theme pathway 1932:1938 arg1 proteins 1940:1947 pathway proteins 1932:1947 pathway proteins 1932:1947 Suppression of pathway proteins by inhibition, RNA silencing, and overexpression confirmed a mechanism for glucose-driven CSC expansion via TET1-O-GlcNAc. 37231419 6 92 theme tumor 957:961 arg1 cells 963:967 tumor cells 957:967 tumor cells 957:967 CSCs are the minor fraction of tumor cells recognized as a source of tumors as well as fueling metastatic recurrence. 37231419 4 93 theme O-linked 684:691 arg1 O-GlcNAc 674:681 the glucose-derived protein modification O-GlcNAc 633:681 the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) 633:712 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 93 theme O-linked 684:691 arg1 N-acetylglucosamine 693:711 O-linked N-acetylglucosamine 684:711 O-linked N-acetylglucosamine 684:711 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 5 94 theme O-GlcNAc 850:857 arg1 roles 833:837 roles 833:837 roles of OGT and O-GlcNAc 833:857 The data in this report implicate roles of OGT and O-GlcNAc within a pathway leading to cancer stem-like cell (CSC) expansion. 37231419 13 95 theme OGT 2135:2137 arg1 production 2139:2148 OGT production 2135:2148 OGT production 2135:2148 Furthermore, activation of the pathway led to higher levels of OGT production via feed-forward regulation in hyperglycemic conditions. 37231419 1 96 theme BACKGROUND 115:124 arg1 metabolism 143:152 BACKGROUND Enhanced glucose metabolism 115:152 BACKGROUND Enhanced glucose metabolism 115:152 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 1 96 theme BACKGROUND 115:124 arg1 feature 159:165 a feature 157:165 a feature of most tumors 157:180 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 17 97 theme TNBC 2720:2723 arg1 risk 2725:2728 pre-menopausal TNBC risk 2705:2728 pre-menopausal TNBC risk 2705:2728 Because pre-menopausal TNBC risk and mortality are correlated with metabolic diseases, our results could lead to new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression. 37231419 8 98 theme cell 1473:1476 arg1 lines 1478:1482 three TNBC cell lines 1462:1482 three TNBC cell lines 1462:1482 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 13 99 theme pathway 2103:2109 arg1 activation 2085:2094 activation 2085:2094 activation of the pathway 2085:2109 Furthermore, activation of the pathway led to higher levels of OGT production via feed-forward regulation in hyperglycemic conditions. 37231419 1 100 theme glucose 135:141 arg1 metabolism 143:152 BACKGROUND Enhanced glucose metabolism 115:152 BACKGROUND Enhanced glucose metabolism 115:152 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 1 100 theme glucose 135:141 arg1 feature 159:165 a feature 157:165 a feature of most tumors 157:180 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 6 101 theme metastatic 1021:1030 arg1 recurrence 1032:1041 metastatic recurrence 1021:1041 metastatic recurrence 1021:1041 CSCs are the minor fraction of tumor cells recognized as a source of tumors as well as fueling metastatic recurrence. 37231419 4 102 link O-linked 684:691 arg1 O-GlcNAc 674:681 the glucose-derived protein modification O-GlcNAc 633:681 the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) 633:712 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 102 link O-linked 684:691 arg1 N-acetylglucosamine 693:711 O-linked N-acetylglucosamine 684:711 O-linked N-acetylglucosamine 684:711 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 3 103 theme hyperglycemic 503:515 arg1 risk 540:543 hyperglycemic disease-coupled cancer risk 503:543 hyperglycemic disease-coupled cancer risk 503:543 However, determining pathways for hyperglycemic disease-coupled cancer risk remains a major unmet need. 37231419 0 104 theme cell 68:71 arg1 pathway 73:79 a cancer stem cell pathway 54:79 a cancer stem cell pathway in triple-negative breast cancer 54:112 Hyperglycemia and O-GlcNAc transferase activity drive a cancer stem cell pathway in triple-negative breast cancer. 37231419 9 105 theme genetic 1515:1521 arg1 models 1523:1528 genetic models 1515:1528 genetic models 1515:1528 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 1 106 theme Enhanced 126:133 arg1 metabolism 143:152 BACKGROUND Enhanced glucose metabolism 115:152 BACKGROUND Enhanced glucose metabolism 115:152 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 1 106 theme Enhanced 126:133 arg1 feature 159:165 a feature 157:165 a feature of most tumors 157:180 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 8 107 theme glucose 1299:1305 arg1 metabolite 1285:1294 a metabolite 1283:1294 a metabolite of glucose 1283:1305 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 8 107 theme glucose 1299:1305 arg1 GlcNAc 1308:1313 GlcNAc 1308:1313 GlcNAc 1308:1313 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 7 108 theme CSC 1207:1209 arg1 factors 1222:1228 CSC tumor risk factors 1207:1228 CSC tumor risk factors 1207:1228 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 7 109 theme tumor 1211:1215 arg1 factors 1222:1228 CSC tumor risk factors 1207:1228 CSC tumor risk factors 1207:1228 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 0 110 theme breast 100:105 arg1 cancer 107:112 triple-negative breast cancer 84:112 triple-negative breast cancer 84:112 Hyperglycemia and O-GlcNAc transferase activity drive a cancer stem cell pathway in triple-negative breast cancer. 37231419 9 111 theme obese 1544:1548 arg1 animals 1550:1556 diet-induced obese animals 1531:1556 diet-induced obese animals 1531:1556 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 7 112 theme hyperglycemic 1178:1190 arg1 conditions 1192:1201 hyperglycemic conditions 1178:1201 hyperglycemic conditions 1178:1201 The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. 37231419 8 113 theme biology 1256:1262 arg1 tools 1264:1268 chemical biology tools 1247:1268 chemical biology tools 1247:1268 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 14 114 from levels 2293:2298 arg1 mice 2303:2306 mice 2303:2306 mice 2303:2306 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 13 115 theme hyperglycemic 2181:2193 arg1 conditions 2195:2204 hyperglycemic conditions 2181:2204 hyperglycemic conditions 2181:2204 Furthermore, activation of the pathway led to higher levels of OGT production via feed-forward regulation in hyperglycemic conditions. 37231419 11 116 theme OGT-catalyzed 1893:1905 arg1 activity 1907:1914 OGT-catalyzed activity 1893:1914 OGT-catalyzed activity 1893:1914 Our data identified that hyperglycemia drove O-GlcNAcylation of the protein TET1 via OGT-catalyzed activity. 37231419 16 117 theme cancer 2648:2653 arg1 risk 2655:2658 hyperglycemia-driven breast cancer risk 2620:2658 hyperglycemia-driven breast cancer risk 2620:2658 This pathway can be potentially targeted to reduce hyperglycemia-driven breast cancer risk, for instance in metabolic diseases. 37231419 9 118 theme chemical 1563:1570 arg1 labeling 1580:1587 chemical biology labeling 1563:1587 chemical biology labeling 1563:1587 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 4 119 theme cellular 587:594 arg1 utilization 602:612 cellular sugar utilization 587:612 cellular sugar utilization 587:612 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 8 120 theme transcriptional 1337:1351 arg1 dioxygenase 1391:1401 the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 1333:1403 the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) 1333:1410 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 8 120 theme transcriptional 1337:1351 arg1 TET1 1406:1409 TET1 1406:1409 TET1 1406:1409 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 2 121 theme pre-menopausal 400:413 arg1 risk 422:425 elevated pre-menopausal cancer risk 391:425 elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC) 391:466 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 0 122 theme transferase 27:37 arg1 activity 39:46 O-GlcNAc transferase activity 18:46 O-GlcNAc transferase activity 18:46 Hyperglycemia and O-GlcNAc transferase activity drive a cancer stem cell pathway in triple-negative breast cancer. 37231419 15 123 theme TNBC 2556:2559 arg1 models 2561:2566 TNBC models 2556:2566 TNBC models 2556:2566 CONCLUSIONS Taken together, our data revealed a mechanism whereby hyperglycemic conditions activated a CSC pathway in TNBC models. 37231419 9 124 from impact 1607:1612 arg1 pathways 1638:1645 CSC pathways 1634:1645 CSC pathways driven by OGT in TNBC model systems 1634:1681 Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. 37231419 4 125 theme utilization 602:612 arg1 addition 621:628 the addition 617:628 the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) 617:712 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 125 theme utilization 602:612 arg1 aspect 577:582 One aspect 573:582 One aspect of cellular sugar utilization 573:612 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 13 126 from regulation 2167:2176 arg1 conditions 2195:2204 hyperglycemic conditions 2181:2204 hyperglycemic conditions 2181:2204 Furthermore, activation of the pathway led to higher levels of OGT production via feed-forward regulation in hyperglycemic conditions. 37231419 8 127 theme protein 1364:1370 arg1 dioxygenase 1391:1401 the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 1333:1403 the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) 1333:1410 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 8 127 theme protein 1364:1370 arg1 TET1 1406:1409 TET1 1406:1409 TET1 1406:1409 METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. 37231419 14 128 theme OGT 2265:2267 arg1 expression 2269:2278 elevated tumor OGT expression and O-GlcNAc levels 2250:2298 expression 2269:2278 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 2 129 theme elevated 391:398 arg1 risk 422:425 elevated pre-menopausal cancer risk 391:425 elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC) 391:466 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 2 130 theme triple-negative 431:445 arg1 TNBC 462:465 TNBC 462:465 TNBC 462:465 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 2 130 theme triple-negative 431:445 arg1 cancer 454:459 triple-negative breast cancer 431:459 triple-negative breast cancer (TNBC) 431:466 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 0 131 theme cancer 56:61 arg1 pathway 73:79 a cancer stem cell pathway 54:79 a cancer stem cell pathway in triple-negative breast cancer 54:112 Hyperglycemia and O-GlcNAc transferase activity drive a cancer stem cell pathway in triple-negative breast cancer. 37231419 17 132 theme OGT 2835:2837 arg1 inhibition 2839:2848 OGT inhibition 2835:2848 OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression 2835:2933 Because pre-menopausal TNBC risk and mortality are correlated with metabolic diseases, our results could lead to new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression. 37231419 17 133 theme TNBC 2900:2903 arg1 tumorigenesis 2905:2917 TNBC tumorigenesis 2900:2917 TNBC tumorigenesis 2900:2917 Because pre-menopausal TNBC risk and mortality are correlated with metabolic diseases, our results could lead to new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression. 37231419 2 134 contain have 336:339 arg1 diseases 296:303 Metabolic diseases 286:303 Metabolic diseases including obesity and diabetes 286:334 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 2 134 contain have 336:339 arg1 diabetes 327:334 diabetes 327:334 diabetes 327:334 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 2 134 contain have 336:339 arg1 obesity 315:321 obesity 315:321 obesity 315:321 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 2 134 contain have 336:339 arg2 component 357:365 a hyperglycemia component 341:365 a hyperglycemia component 341:365 Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). 37231419 4 135 theme glucose-derived 637:651 arg1 O-GlcNAc 674:681 the glucose-derived protein modification O-GlcNAc 633:681 the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) 633:712 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 135 theme glucose-derived 637:651 arg1 N-acetylglucosamine 693:711 O-linked N-acetylglucosamine 684:711 O-linked N-acetylglucosamine 684:711 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 3 136 theme disease-coupled 517:531 arg1 risk 540:543 hyperglycemic disease-coupled cancer risk 503:543 hyperglycemic disease-coupled cancer risk 503:543 However, determining pathways for hyperglycemic disease-coupled cancer risk remains a major unmet need. 37231419 1 137 theme glucose 229:235 arg1 flux 237:240 aberrant glucose flux 220:240 aberrant glucose flux 220:240 BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. 37231419 0 138 from pathway 73:79 arg1 cancer 107:112 triple-negative breast cancer 84:112 triple-negative breast cancer 84:112 Hyperglycemia and O-GlcNAc transferase activity drive a cancer stem cell pathway in triple-negative breast cancer. 37231419 4 139 theme modification 661:672 arg1 O-GlcNAc 674:681 the glucose-derived protein modification O-GlcNAc 633:681 the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) 633:712 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 4 139 theme modification 661:672 arg1 N-acetylglucosamine 693:711 O-linked N-acetylglucosamine 684:711 O-linked N-acetylglucosamine 684:711 One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). 37231419 14 140 theme TNBC 2415:2418 arg1 microenvironment 2420:2435 the hyperglycemic TNBC microenvironment 2397:2435 the hyperglycemic TNBC microenvironment 2397:2435 We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. 37231419 3 141 theme unmet 561:565 arg1 need 567:570 a major unmet need 553:570 a major unmet need 553:570 However, determining pathways for hyperglycemic disease-coupled cancer risk remains a major unmet need. 37188682 8 0 from mice 1175:1178 arg1 impairment 1137:1146 the impairment 1133:1146 the impairment of spermatogenesis in aged mice 1133:1178 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 7 1 theme meiotic 948:954 arg1 initiation 956:965 meiotic initiation 948:965 meiotic initiation 948:965 O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. 37188682 1 2 theme critical 133:140 arg1 issue 149:153 a critical social issue 131:153 a critical social issue 131:153 In recent years, the postponement of childbearing has become a critical social issue. 37188682 4 3 theme various 493:499 arg1 systems 501:507 various systems 493:507 various systems 493:507 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 6 4 theme aged 778:781 arg1 mice 783:786 aged mice 778:786 aged mice 778:786 Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. 37188682 7 5 theme crucial 932:938 arg1 role 940:943 its crucial role 928:943 its crucial role in meiotic initiation and progression 928:981 O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. 37188682 1 6 theme social 142:147 arg1 issue 149:153 a critical social issue 131:153 a critical social issue 131:153 In recent years, the postponement of childbearing has become a critical social issue. 37188682 9 7 theme O-GlcNAc 1215:1222 arg1 elevation 1202:1210 the elevation 1198:1210 the elevation of O-GlcNAc in the testis 1198:1236 Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. 37188682 8 8 theme O-GlcNAc 1023:1030 arg1 elevation 1010:1018 the age-related elevation 994:1018 the age-related elevation of O-GlcNAc in young mice 994:1044 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 11 9 theme posttranslational 1528:1544 arg1 impairment 1611:1620 the impairment 1607:1620 the impairment of spermatogenesis 1607:1639 Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging. 37188682 11 9 theme posttranslational 1528:1544 arg1 modification 1546:1557 a novel posttranslational modification 1520:1557 a novel posttranslational modification 1520:1557 Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging. 37188682 10 10 theme decreasing 1331:1340 arg1 O-GlcNAc 1342:1349 decreasing O-GlcNAc 1331:1349 decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor 1331:1410 Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. 37188682 4 11 link O-linked 356:363 arg1 O-GlcNAc 386:393 O-GlcNAc 386:393 O-GlcNAc 386:393 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 4 11 link O-linked 356:363 arg1 N-acetylglucosamine 365:383 O-linked N-acetylglucosamine 356:383 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) 313:394 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 8 12 theme inhibitor 1096:1104 arg1 Thiamet-G 1106:1114 the chemical inhibitor Thiamet-G 1083:1114 the chemical inhibitor Thiamet-G 1083:1114 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 8 13 theme spermatogenesis 1151:1165 arg1 impairment 1137:1146 the impairment 1133:1146 the impairment of spermatogenesis in aged mice 1133:1178 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 0 14 from arrest 49:54 arg1 mice 64:67 male mice 59:67 male mice 59:67 Age-related elevation of O-GlcNAc causes meiotic arrest in male mice. 37188682 4 15 from process 473:479 arg1 systems 501:507 various systems 493:507 various systems 493:507 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 6 16 from decline 748:754 arg1 mice 783:786 aged mice 778:786 aged mice 778:786 Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. 37188682 6 16 from decline 748:754 arg1 spermatogenesis 759:773 spermatogenesis 759:773 spermatogenesis 759:773 Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. 37188682 5 17 theme O-GlcNAc 689:696 arg1 role 681:684 the role 677:684 the role of O-GlcNAc in spermatogenesis 677:715 Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. 37188682 8 18 theme aged 1170:1173 arg1 mice 1175:1178 aged mice 1170:1178 aged mice 1170:1178 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 6 19 theme O-GlcNAc 820:827 arg1 elevation 807:815 elevation 807:815 elevation of O-GlcNAc 807:827 Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. 37188682 10 20 theme age-related 1437:1447 arg1 impairment 1449:1458 the age-related impairment 1433:1458 the age-related impairment of spermatogenesis 1433:1477 Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. 37188682 1 21 theme recent 73:78 arg1 years 80:84 recent years 73:84 recent years 73:84 In recent years, the postponement of childbearing has become a critical social issue. 37188682 0 22 theme Age-related 0:10 arg1 elevation 12:20 Age-related elevation 0:20 Age-related elevation of O-GlcNAc 0:32 Age-related elevation of O-GlcNAc causes meiotic arrest in male mice. 37188682 11 23 theme novel 1522:1526 arg1 impairment 1611:1620 the impairment 1607:1620 the impairment of spermatogenesis 1607:1639 Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging. 37188682 11 23 theme novel 1522:1526 arg1 modification 1546:1557 a novel posttranslational modification 1520:1557 a novel posttranslational modification 1520:1557 Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging. 37188682 9 24 theme meiotic 1247:1253 arg1 arrest 1265:1270 meiotic pachytene arrest 1247:1270 meiotic pachytene arrest 1247:1270 Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. 37188682 8 25 theme young 1035:1039 arg1 mice 1041:1044 young mice 1035:1044 young mice 1035:1044 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 5 26 with alteration 631:640 arg1 aging 659:663 aging 659:663 aging 659:663 Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. 37188682 0 27 theme O-GlcNAc 25:32 arg1 elevation 12:20 Age-related elevation 0:20 Age-related elevation of O-GlcNAc 0:32 Age-related elevation of O-GlcNAc causes meiotic arrest in male mice. 37188682 10 28 theme transferase 1384:1394 arg1 inhibitor 1402:1410 an O-GlcNAc transferase (OGT) inhibitor 1372:1410 an O-GlcNAc transferase (OGT) inhibitor 1372:1410 Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. 37188682 4 29 dep modification 343:354 arg1 O-GlcNAc 386:393 O-GlcNAc 386:393 O-GlcNAc 386:393 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 4 29 dep modification 343:354 arg1 N-acetylglucosamine 365:383 O-linked N-acetylglucosamine 356:383 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) 313:394 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 10 30 from O-GlcNAc 1342:1349 arg1 testes 1359:1364 aged testes 1354:1364 aged testes using an O-GlcNAc transferase (OGT) inhibitor 1354:1410 Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. 37188682 11 31 theme spermatogenesis 1625:1639 arg1 impairment 1611:1620 the impairment 1607:1620 the impairment of spermatogenesis 1607:1639 Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging. 37188682 11 31 theme spermatogenesis 1625:1639 arg1 modification 1546:1557 a novel posttranslational modification 1520:1557 a novel posttranslational modification 1520:1557 Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging. 37188682 8 32 from elevation 1010:1018 arg1 mice 1041:1044 young mice 1035:1044 young mice 1035:1044 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 11 33 theme meiotic 1576:1582 arg1 progression 1584:1594 meiotic progression 1576:1594 meiotic progression 1576:1594 Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging. 37188682 4 34 dep testis 554:559 arg1 the 550:552 the 550:552 the 550:552 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 7 35 from role 940:943 arg1 initiation 956:965 meiotic initiation 948:965 meiotic initiation 948:965 O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. 37188682 7 35 from role 940:943 arg1 progression 971:981 progression 971:981 progression 971:981 O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. 37188682 0 36 theme meiotic 41:47 arg1 arrest 49:54 meiotic arrest 41:54 meiotic arrest in male mice 41:67 Age-related elevation of O-GlcNAc causes meiotic arrest in male mice. 37188682 10 37 theme O-GlcNAc 1375:1382 arg1 OGT 1397:1399 OGT 1397:1399 OGT 1397:1399 Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. 37188682 10 37 theme O-GlcNAc 1375:1382 arg1 transferase 1384:1394 O-GlcNAc transferase 1375:1394 an O-GlcNAc transferase (OGT) inhibitor 1372:1410 Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. 37188682 2 38 theme Male 156:159 arg1 fertility 161:169 Male fertility 156:169 Male fertility 156:169 Male fertility is negatively associated with age because of testis aging. 37188682 2 39 theme testis 216:221 arg1 aging 223:227 testis aging 216:227 testis aging 216:227 Male fertility is negatively associated with age because of testis aging. 37188682 10 40 theme spermatogenesis 1463:1477 arg1 impairment 1449:1458 the age-related impairment 1433:1458 the age-related impairment of spermatogenesis 1433:1477 Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. 37188682 9 41 from defects 1279:1285 arg1 recombination 1303:1315 recombination 1303:1315 recombination 1303:1315 Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. 37188682 9 41 from defects 1279:1285 arg1 synapsis 1290:1297 synapsis 1290:1297 synapsis 1290:1297 Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. 37188682 4 42 theme posttranslational 325:341 arg1 type 408:411 a type 406:411 a type of monosaccharide modification 406:442 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 4 42 theme posttranslational 325:341 arg1 modification 343:354 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) 313:394 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) 313:394 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 3 43 theme molecular 276:284 arg1 mechanism 286:294 the molecular mechanism 272:294 the molecular mechanism 272:294 Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. 37188682 5 44 from role 681:684 arg1 spermatogenesis 701:715 spermatogenesis 701:715 spermatogenesis 701:715 Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. 37188682 4 45 theme dynamic 317:323 arg1 type 408:411 a type 406:411 a type of monosaccharide modification 406:442 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 4 45 theme dynamic 317:323 arg1 modification 343:354 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) 313:394 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) 313:394 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 9 46 theme pachytene 1255:1263 arg1 arrest 1265:1270 meiotic pachytene arrest 1247:1270 meiotic pachytene arrest 1247:1270 Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. 37188682 8 47 from spermatogenesis 1151:1165 arg1 mice 1175:1178 aged mice 1170:1178 aged mice 1170:1178 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 4 48 theme O-linked 356:363 arg1 O-GlcNAc 386:393 O-GlcNAc 386:393 O-GlcNAc 386:393 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 4 48 theme O-linked 356:363 arg1 N-acetylglucosamine 365:383 O-linked N-acetylglucosamine 356:383 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) 313:394 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 9 49 from elevation 1202:1210 arg1 testis 1231:1236 the testis 1227:1236 the testis 1227:1236 Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. 37188682 8 50 theme chemical 1087:1094 arg1 Thiamet-G 1106:1114 the chemical inhibitor Thiamet-G 1083:1114 the chemical inhibitor Thiamet-G 1083:1114 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 1 51 theme childbearing 107:118 arg1 postponement 91:102 the postponement 87:102 the postponement of childbearing 87:118 In recent years, the postponement of childbearing has become a critical social issue. 37188682 4 52 theme male 565:568 arg1 aging 583:587 male reproductive aging 565:587 male reproductive aging 565:587 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 5 53 theme O-GlcNAc 645:652 arg1 alteration 631:640 the alteration 627:640 the alteration of O-GlcNAc with aging 627:663 Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. 37188682 4 54 theme modification 431:442 arg1 type 408:411 a type 406:411 a type of monosaccharide modification 406:442 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 4 54 theme modification 431:442 arg1 modification 343:354 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) 313:394 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) 313:394 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 10 55 theme aged 1354:1357 arg1 testes 1359:1364 aged testes 1354:1364 aged testes using an O-GlcNAc transferase (OGT) inhibitor 1354:1410 Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. 37188682 4 56 theme monosaccharide 416:429 arg1 modification 431:442 monosaccharide modification 416:442 monosaccharide modification 416:442 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 8 57 from impairment 1137:1146 arg1 mice 1175:1178 aged mice 1170:1178 aged mice 1170:1178 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 8 58 theme age-related 998:1008 arg1 elevation 1010:1018 the age-related elevation 994:1018 the age-related elevation of O-GlcNAc in young mice 994:1044 Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. 37188682 0 59 theme male 59:62 arg1 mice 64:67 male mice 59:67 male mice 59:67 Age-related elevation of O-GlcNAc causes meiotic arrest in male mice. 37188682 4 60 theme aging 484:488 arg1 process 473:479 the process 469:479 the process of aging in various systems 469:507 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 37188682 4 61 theme reproductive 570:581 arg1 aging 583:587 male reproductive aging 565:587 male reproductive aging 565:587 The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. 36054098 7 0 theme ubiquitous 1167:1176 arg1 modification 1218:1229 a ubiquitous and underappreciated post-translational modification 1165:1229 a ubiquitous and underappreciated post-translational modification 1165:1229 Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. 36054098 7 0 theme ubiquitous 1167:1176 arg1 it 1159:1160 it 1159:1160 it 1159:1160 Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. 36054098 6 1 theme region 864:869 arg1 structure 838:846 a crystal structure 828:846 a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity 828:1046 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 6 2 theme high 1018:1021 arg1 affinity 1023:1030 high affinity 1018:1030 high affinity 1018:1030 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 1 3 theme vital 165:169 arg1 modification 190:201 a vital post-translational modification 163:201 a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions 163:310 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 1 3 theme vital 165:169 arg1 Glycosylation 146:158 Glycosylation 146:158 Glycosylation 146:158 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 0 4 theme O-GalNAcylation 88:102 arg1 Development 0:10 Development 0:10 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody 0:60 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 0 4 theme O-GalNAcylation 88:102 arg1 Detection 66:74 Detection 66:74 Detection of Tyrosine O-GalNAcylation 66:102 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 6 5 theme Fab 860:862 arg1 region 864:869 the G10C Fab region 851:869 the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity 851:1046 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 1 6 theme post-translational 171:188 arg1 modification 190:201 a vital post-translational modification 163:201 a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions 163:310 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 1 6 theme post-translational 171:188 arg1 Glycosylation 146:158 Glycosylation 146:158 Glycosylation 146:158 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 0 7 theme Human 116:120 arg1 Tissues 122:128 Numerous Human Tissues 107:128 Numerous Human Tissues 107:128 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 0 8 from Development 0:10 arg1 Tissues 122:128 Numerous Human Tissues 107:128 Numerous Human Tissues 107:128 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 0 8 from Development 0:10 arg1 Lines 139:143 Cell Lines 134:143 Cell Lines 134:143 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 9 9 located observed 1406:1413 arg2 GalNAc-Tyr 1386:1395 GalNAc-Tyr 1386:1395 GalNAc-Tyr 1386:1395 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 9 located observed 1406:1413 arg1 variety 1420:1426 a variety 1418:1426 a variety of cell lines and primary cells 1418:1458 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 9 located observed 1406:1413 arg1 lines 1436:1440 cell lines 1431:1440 cell lines 1431:1440 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 9 located observed 1406:1413 arg1 cells 1454:1458 primary cells 1446:1458 primary cells 1446:1458 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 10 theme cancer 1521:1526 arg1 lines 1533:1537 certain cancer cell lines 1513:1537 certain cancer cell lines 1513:1537 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 11 located present 1473:1479 arg1 lines 1533:1537 certain cancer cell lines 1513:1537 certain cancer cell lines 1513:1537 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 11 located present 1473:1479 arg1 surface 1502:1508 the external cell surface 1484:1508 the external cell surface 1484:1508 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 11 located present 1473:1479 arg2 GalNAc-Tyr 1386:1395 GalNAc-Tyr 1386:1395 GalNAc-Tyr 1386:1395 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 0 12 theme Numerous 107:114 arg1 Tissues 122:128 Numerous Human Tissues 107:128 Numerous Human Tissues 107:128 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 0 13 from Detection 66:74 arg1 Tissues 122:128 Numerous Human Tissues 107:128 Numerous Human Tissues 107:128 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 0 13 from Detection 66:74 arg1 Lines 139:143 Cell Lines 134:143 Cell Lines 134:143 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 6 14 from region 864:869 arg1 complex 874:880 complex 874:880 complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity 874:1046 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 9 15 theme cell 1528:1531 arg1 lines 1533:1537 certain cancer cell lines 1513:1537 certain cancer cell lines 1513:1537 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 1 16 theme cell-cell 289:297 arg1 interactions 299:310 cell-cell interactions 289:310 cell-cell interactions 289:310 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 5 17 contain has 720:722 arg2 selectivity 783:793 excellent selectivity 773:793 excellent selectivity for GalNAc-Tyr 773:808 The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. 36054098 5 17 contain has 720:722 arg1 G10C 714:717 G10C 714:717 G10C 714:717 The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. 36054098 5 17 contain has 720:722 arg2 affinity 742:749 an unusually high affinity 724:749 an unusually high affinity (app KD = 100 pM) 724:767 The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. 36054098 5 17 contain has 720:722 arg1 antibody 704:711 The antibody 700:711 The antibody 700:711 The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. 36054098 5 18 dep = 759:759 arg1 pM 765:766 100 pM 761:766 100 pM 761:766 The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. 36054098 4 19 theme GalNAc-Tyr-derived 604:621 arg1 hapten 623:628 a GalNAc-Tyr-derived hapten 602:628 a GalNAc-Tyr-derived hapten 602:628 Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. 36054098 2 20 theme tyrosine 408:415 arg1 oxygen 398:403 the side-chain oxygen 383:403 the side-chain oxygen of tyrosine 383:415 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 9 21 theme cells 1454:1458 arg1 variety 1420:1426 a variety 1418:1426 a variety of cell lines and primary cells 1418:1458 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 21 theme cells 1454:1458 arg1 lines 1436:1440 cell lines 1431:1440 cell lines 1431:1440 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 21 theme cells 1454:1458 arg1 cells 1454:1458 primary cells 1446:1458 primary cells 1446:1458 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 6 22 with complex 874:880 arg1 4-nitrophenyl-N-acetyl-α-d-galactosaminide 887:928 4-nitrophenyl-N-acetyl-α-d-galactosaminide 887:928 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity 887:1046 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 9 23 theme cell 1497:1500 arg1 surface 1502:1508 the external cell surface 1484:1508 the external cell surface 1484:1508 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 2 24 dep wherein 375:381 arg1 modified 420:427 modified 420:427 is modified with a GalNAc residue (GalNAc-Tyr) 417:462 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 9 25 theme lines 1436:1440 arg1 variety 1420:1426 a variety 1418:1426 a variety of cell lines and primary cells 1418:1458 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 25 theme lines 1436:1440 arg1 lines 1436:1440 cell lines 1431:1440 cell lines 1431:1440 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 25 theme lines 1436:1440 arg1 cells 1454:1458 primary cells 1446:1458 primary cells 1446:1458 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 6 26 theme crystal 830:836 arg1 structure 838:846 a crystal structure 828:846 a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity 828:1046 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 7 27 theme underappreciated 1182:1197 arg1 modification 1218:1229 a ubiquitous and underappreciated post-translational modification 1165:1229 a ubiquitous and underappreciated post-translational modification 1165:1229 Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. 36054098 7 27 theme underappreciated 1182:1197 arg1 it 1159:1160 it 1159:1160 it 1159:1160 Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. 36054098 8 28 theme cell-specific 1364:1376 arg1 manner 1378:1383 a cell-specific manner 1362:1383 a cell-specific manner 1362:1383 Localization to specific cell types and organ substructures within those tissues indicates that GalNAc-Tyr is likely regulated in a cell-specific manner. 36054098 9 29 from present 1473:1479 arg1 lines 1533:1537 certain cancer cell lines 1513:1537 certain cancer cell lines 1513:1537 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 2 30 theme new 324:326 arg1 type 328:331 a new type 322:331 a new type of O-linked glycosylation 322:357 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 8 31 theme specific 1248:1255 arg1 types 1262:1266 specific cell types 1248:1266 specific cell types 1248:1266 Localization to specific cell types and organ substructures within those tissues indicates that GalNAc-Tyr is likely regulated in a cell-specific manner. 36054098 2 32 theme side-chain 387:396 arg1 oxygen 398:403 the side-chain oxygen 383:403 the side-chain oxygen of tyrosine 383:415 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 0 33 theme GalNAc-Tyrosine-Specific 17:40 arg1 Antibody 53:60 a GalNAc-Tyrosine-Specific Monoclonal Antibody 15:60 a GalNAc-Tyrosine-Specific Monoclonal Antibody 15:60 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 5 34 dep affinity 742:749 arg1 KD 756:757 app KD 752:757 app KD = 100 pM 752:766 The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. 36054098 9 35 theme cell 1431:1434 arg1 lines 1436:1440 cell lines 1431:1440 cell lines 1431:1440 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 36 theme GalNAc-Tyr 1556:1565 arg1 localization 1567:1578 GalNAc-Tyr localization 1556:1578 GalNAc-Tyr localization 1556:1578 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 2 37 mod modified 420:427 arg3 residue 443:449 a GalNAc residue 434:449 a GalNAc residue (GalNAc-Tyr) 434:462 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 2 37 mod modified 420:427 arg1 oxygen 398:403 the side-chain oxygen 383:403 the side-chain oxygen of tyrosine 383:415 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 2 37 mod modified 420:427 arg3 GalNAc-Tyr 452:461 GalNAc-Tyr 452:461 GalNAc-Tyr 452:461 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 4 38 theme hapten 623:628 arg1 synthesis 589:597 synthesis 589:597 synthesis 589:597 Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. 36054098 4 38 theme hapten 623:628 arg1 design 578:583 design 578:583 design 578:583 Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. 36054098 4 38 theme hapten 623:628 arg1 use 638:640 its use 634:640 its use in generating a GalNAc-Tyr selective monoclonal antibody 634:697 Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. 36054098 2 39 theme GalNAc 436:441 arg1 GalNAc-Tyr 452:461 GalNAc-Tyr 452:461 GalNAc-Tyr 452:461 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 2 39 theme GalNAc 436:441 arg1 residue 443:449 a GalNAc residue 434:449 a GalNAc residue (GalNAc-Tyr) 434:462 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 6 40 theme small 933:937 arg1 molecule 939:946 a small molecule 931:946 a small molecule mimic of GalNAc-Tyr 931:966 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 0 41 theme Cell 134:137 arg1 Lines 139:143 Cell Lines 134:143 Cell Lines 134:143 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 4 42 theme monoclonal 679:688 arg1 antibody 690:697 a GalNAc-Tyr selective monoclonal antibody 656:697 a GalNAc-Tyr selective monoclonal antibody 656:697 Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. 36054098 9 43 theme certain 1513:1519 arg1 lines 1533:1537 certain cancer cell lines 1513:1537 certain cancer cell lines 1513:1537 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 4 44 theme selective 669:677 arg1 antibody 690:697 a GalNAc-Tyr selective monoclonal antibody 656:697 a GalNAc-Tyr selective monoclonal antibody 656:697 Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. 36054098 0 45 theme Antibody 53:60 arg1 Development 0:10 Development 0:10 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody 0:60 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 0 45 theme Antibody 53:60 arg1 Detection 66:74 Detection 66:74 Detection of Tyrosine O-GalNAcylation 66:102 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 8 46 theme organ 1272:1276 arg1 substructures 1278:1290 organ substructures 1272:1290 organ substructures 1272:1290 Localization to specific cell types and organ substructures within those tissues indicates that GalNAc-Tyr is likely regulated in a cell-specific manner. 36054098 9 47 theme primary 1446:1452 arg1 cells 1454:1458 primary cells 1446:1458 primary cells 1446:1458 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 1 48 theme biological 226:235 arg1 folding 265:271 protein folding 257:271 protein folding 257:271 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 1 48 theme biological 226:235 arg1 interactions 299:310 cell-cell interactions 289:310 cell-cell interactions 289:310 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 1 48 theme biological 226:235 arg1 signaling 274:282 signaling 274:282 signaling 274:282 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 1 48 theme biological 226:235 arg1 processes 237:245 biological processes 226:245 biological processes including protein folding, signaling, and cell-cell interactions 226:310 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 0 49 theme Monoclonal 42:51 arg1 Antibody 53:60 a GalNAc-Tyrosine-Specific Monoclonal Antibody 15:60 a GalNAc-Tyrosine-Specific Monoclonal Antibody 15:60 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 7 50 theme most 1123:1126 arg1 tissues 1134:1140 most human tissues 1123:1140 most human tissues 1123:1140 Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. 36054098 7 51 theme human 1128:1132 arg1 tissues 1134:1140 most human tissues 1123:1140 most human tissues 1123:1140 Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. 36054098 9 52 attach present 1473:1479 arg1 lines 1533:1537 certain cancer cell lines 1513:1537 certain cancer cell lines 1513:1537 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 52 attach present 1473:1479 arg2 GalNAc-Tyr 1386:1395 GalNAc-Tyr 1386:1395 GalNAc-Tyr 1386:1395 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 9 52 attach present 1473:1479 arg1 surface 1502:1508 the external cell surface 1484:1508 the external cell surface 1484:1508 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 1 53 theme processes 237:245 arg1 folding 265:271 protein folding 257:271 protein folding 257:271 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 1 53 theme processes 237:245 arg1 interactions 299:310 cell-cell interactions 289:310 cell-cell interactions 289:310 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 1 53 theme processes 237:245 arg1 signaling 274:282 signaling 274:282 signaling 274:282 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 1 53 theme processes 237:245 arg1 range 217:221 a range 215:221 a range of biological processes including protein folding, signaling, and cell-cell interactions 215:310 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 5 54 theme = 759:759 arg1 KD 756:757 app KD 752:757 app KD = 100 pM 752:766 The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. 36054098 6 55 from structure 838:846 arg1 complex 874:880 complex 874:880 complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity 874:1046 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 6 56 dep 4-nitrophenyl-N-acetyl-α-d-galactosaminide 887:928 arg1 molecule 939:946 a small molecule 931:946 a small molecule mimic of GalNAc-Tyr 931:966 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 10 57 theme glycosylation 1683:1695 arg1 form 1675:1678 this under-studied form 1656:1678 this under-studied form of glycosylation 1656:1695 Collectively, the results shed new light on this under-studied form of glycosylation and provide access to new tools that will enable expanded biochemical and clinical investigations. 36054098 6 58 theme G10C 855:858 arg1 region 864:869 the G10C Fab region 851:869 the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity 851:1046 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 6 59 from complex 874:880 arg1 structure 838:846 a crystal structure 828:846 a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity 828:1046 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 10 60 theme clinical 1771:1778 arg1 investigations 1780:1793 expanded biochemical and clinical investigations 1746:1793 expanded biochemical and clinical investigations 1746:1793 Collectively, the results shed new light on this under-studied form of glycosylation and provide access to new tools that will enable expanded biochemical and clinical investigations. 36054098 2 61 theme glycosylation 345:357 arg1 type 328:331 a new type 322:331 a new type of O-linked glycosylation 322:357 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 10 62 theme expanded 1746:1753 arg1 investigations 1780:1793 expanded biochemical and clinical investigations 1746:1793 expanded biochemical and clinical investigations 1746:1793 Collectively, the results shed new light on this under-studied form of glycosylation and provide access to new tools that will enable expanded biochemical and clinical investigations. 36054098 9 63 theme cancer 1598:1603 arg1 cells 1605:1609 cancer cells 1598:1609 cancer cells 1598:1609 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 10 64 theme biochemical 1755:1765 arg1 investigations 1780:1793 expanded biochemical and clinical investigations 1746:1793 expanded biochemical and clinical investigations 1746:1793 Collectively, the results shed new light on this under-studied form of glycosylation and provide access to new tools that will enable expanded biochemical and clinical investigations. 36054098 2 65 theme O-linked 336:343 arg1 glycosylation 345:357 O-linked glycosylation 336:357 O-linked glycosylation 336:357 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 10 66 theme under-studied 1661:1673 arg1 form 1675:1678 this under-studied form 1656:1678 this under-studied form of glycosylation 1656:1695 Collectively, the results shed new light on this under-studied form of glycosylation and provide access to new tools that will enable expanded biochemical and clinical investigations. 36054098 6 67 theme structural 997:1006 arg1 basis 1008:1012 the structural basis 993:1012 the structural basis for high affinity and selectivity 993:1046 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 10 68 theme new 1719:1721 arg1 tools 1723:1727 new tools 1719:1727 new tools that will enable expanded biochemical and clinical investigations 1719:1793 Collectively, the results shed new light on this under-studied form of glycosylation and provide access to new tools that will enable expanded biochemical and clinical investigations. 36054098 5 69 theme excellent 773:781 arg1 selectivity 783:793 excellent selectivity 773:793 excellent selectivity for GalNAc-Tyr 773:808 The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. 36054098 10 70 theme new 1643:1645 arg1 light 1647:1651 new light 1643:1651 new light 1643:1651 Collectively, the results shed new light on this under-studied form of glycosylation and provide access to new tools that will enable expanded biochemical and clinical investigations. 36054098 9 71 theme external 1488:1495 arg1 surface 1502:1508 the external cell surface 1484:1508 the external cell surface 1484:1508 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36054098 1 72 theme protein 257:263 arg1 folding 265:271 protein folding 257:271 protein folding 257:271 Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. 36054098 0 73 theme Tyrosine 79:86 arg1 O-GalNAcylation 88:102 Tyrosine O-GalNAcylation 79:102 Tyrosine O-GalNAcylation 79:102 Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines. 36054098 6 74 dep molecule 939:946 arg1 mimic 948:952 mimic 948:952 mimic of GalNAc-Tyr 948:966 We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. 36054098 8 75 theme cell 1257:1260 arg1 types 1262:1266 specific cell types 1248:1266 specific cell types 1248:1266 Localization to specific cell types and organ substructures within those tissues indicates that GalNAc-Tyr is likely regulated in a cell-specific manner. 36054098 3 76 theme GalNAc-Tyr 504:513 arg1 prevalence 515:524 GalNAc-Tyr prevalence 504:524 GalNAc-Tyr prevalence 504:524 At present, very little is known about GalNAc-Tyr prevalence, function, or biosynthesis. 36054098 7 77 theme post-translational 1199:1216 arg1 modification 1218:1229 a ubiquitous and underappreciated post-translational modification 1165:1229 a ubiquitous and underappreciated post-translational modification 1165:1229 Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. 36054098 7 77 theme post-translational 1199:1216 arg1 it 1159:1160 it 1159:1160 it 1159:1160 Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. 36054098 5 78 theme high 737:740 arg1 affinity 742:749 an unusually high affinity 724:749 an unusually high affinity (app KD = 100 pM) 724:767 The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. 36054098 2 79 link O-linked 336:343 arg1 glycosylation 345:357 O-linked glycosylation 336:357 O-linked glycosylation 336:357 In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). 36054098 4 80 link GalNAc-Tyr-derived 604:621 arg1 hapten 623:628 a GalNAc-Tyr-derived hapten 602:628 a GalNAc-Tyr-derived hapten 602:628 Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. 36054098 4 81 theme GalNAc-Tyr 658:667 arg1 antibody 690:697 a GalNAc-Tyr selective monoclonal antibody 656:697 a GalNAc-Tyr selective monoclonal antibody 656:697 Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. 36054098 9 82 from lines 1533:1537 arg1 present 1473:1479 present 1473:1479 present 1473:1479 GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. 36266488 6 0 theme chromatin 1280:1288 arg1 modulation 1290:1299 direct chromatin modulation 1273:1299 direct chromatin modulation 1273:1299 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 6 1 theme normal 1241:1246 arg1 cells 1259:1263 normal and tumour cells 1241:1263 normal and tumour cells 1241:1263 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 2 2 theme fructose-1,6-bisphosphatase 420:446 arg1 phosphorylation 462:476 PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation 406:476 PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation 406:476 Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. 36266488 2 3 theme localization 548:559 arg1 signal 561:566 its nuclear localization signal 536:566 its nuclear localization signal for nuclear translocation 536:592 Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. 36266488 1 4 theme greater 185:191 arg1 plasticity 203:212 greater metabolic plasticity 185:212 greater metabolic plasticity than normal cells 185:230 Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. 36266488 2 5 from deprivation 364:374 arg1 hepatocytes 386:396 normal hepatocytes 379:396 normal hepatocytes 379:396 Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. 36266488 0 6 theme PPARα-regulated 110:124 arg1 growth 156:161 tumour growth 149:161 tumour growth 149:161 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 6 theme PPARα-regulated 110:124 arg1 Fructose-1,6-bisphosphatase 0:26 Fructose-1,6-bisphosphatase 1 0:28 Fructose-1,6-bisphosphatase 1 0:28 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 6 theme PPARα-regulated 110:124 arg1 phosphatase 53:63 a protein phosphatase 43:63 a protein phosphatase 43:63 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 6 theme PPARα-regulated 110:124 arg1 transcription 131:143 PPARα-regulated gene transcription 110:143 PPARα-regulated gene transcription 110:143 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 6 7 from role 1206:1209 arg1 cells 1259:1263 normal and tumour cells 1241:1263 normal and tumour cells 1241:1263 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 6 7 from role 1206:1209 arg1 regulation 1227:1236 gene regulation 1222:1236 gene regulation 1222:1236 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 6 8 from regulation 1227:1236 arg1 role 1206:1209 the differential role 1189:1209 the differential role of FBP1 in gene regulation in normal and tumour cells 1189:1263 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 5 9 theme S170 1020:1023 arg1 phosphorylation 1025:1039 FBP1 S170 phosphorylation 1015:1039 FBP1 S170 phosphorylation 1015:1039 In addition, FBP1 S170 phosphorylation inversely correlates with β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. 36266488 4 10 theme hepatocellular 869:882 arg1 cells 894:898 hepatocellular carcinoma cells 869:898 hepatocellular carcinoma cells 869:898 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 6 11 theme function 1360:1367 arg1 inactivation 1320:1331 the inactivation 1316:1331 the inactivation of its protein phosphatase function in tumour growth 1316:1384 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 5 12 theme gene 1079:1082 arg1 expression 1084:1093 β-oxidation gene expression 1067:1093 β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration 1067:1161 In addition, FBP1 S170 phosphorylation inversely correlates with β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. 36266488 4 13 link O-linked 825:832 arg1 transferase 854:864 overexpressed O-linked N-acetylglucosamine transferase 811:864 overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells 811:898 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 1 14 theme defined 311:317 arg1 mechanisms 319:328 unclearly defined mechanisms 301:328 unclearly defined mechanisms 301:328 Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. 36266488 3 15 theme nuclear 608:614 arg1 FBP1 616:619 nuclear FBP1 608:619 nuclear FBP1 608:619 Importantly, nuclear FBP1 binds PPARα and functions as a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated β-oxidation gene expression. 36266488 3 15 theme nuclear 608:614 arg1 phosphatase 660:670 a protein phosphatase 650:670 a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated β-oxidation gene expression 650:764 Importantly, nuclear FBP1 binds PPARα and functions as a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated β-oxidation gene expression. 36266488 4 16 from contrast 770:777 arg1 O-GlcNAcylated 793:806 O-GlcNAcylated 793:806 O-GlcNAcylated 793:806 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 1 17 theme metabolic 193:201 arg1 plasticity 203:212 greater metabolic plasticity 185:212 greater metabolic plasticity than normal cells 185:230 Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. 36266488 0 18 theme gene 126:129 arg1 growth 156:161 tumour growth 149:161 tumour growth 149:161 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 18 theme gene 126:129 arg1 Fructose-1,6-bisphosphatase 0:26 Fructose-1,6-bisphosphatase 1 0:28 Fructose-1,6-bisphosphatase 1 0:28 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 18 theme gene 126:129 arg1 phosphatase 53:63 a protein phosphatase 43:63 a protein phosphatase 43:63 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 18 theme gene 126:129 arg1 transcription 131:143 PPARα-regulated gene transcription 110:143 PPARα-regulated gene transcription 110:143 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 2 19 theme nuclear 540:546 arg1 signal 561:566 its nuclear localization signal 536:566 its nuclear localization signal for nuclear translocation 536:592 Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. 36266488 6 20 from FBP1 1214:1217 arg1 regulation 1227:1236 gene regulation 1222:1236 gene regulation 1222:1236 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 5 21 theme survival 1145:1152 arg1 duration 1154:1161 patient survival duration 1137:1161 patient survival duration 1137:1161 In addition, FBP1 S170 phosphorylation inversely correlates with β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. 36266488 6 22 theme tumour 1252:1257 arg1 cells 1259:1263 normal and tumour cells 1241:1263 normal and tumour cells 1241:1263 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 2 23 theme S170 457:460 arg1 phosphorylation 462:476 PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation 406:476 PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation 406:476 Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. 36266488 2 24 theme nuclear 572:578 arg1 translocation 580:592 nuclear translocation 572:592 nuclear translocation 572:592 Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. 36266488 4 25 theme tumour 987:992 arg1 growth 994:999 tumour growth 987:999 tumour growth 987:999 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 2 26 theme glucose 356:362 arg1 deprivation 364:374 glucose deprivation 356:374 glucose deprivation in normal hepatocytes 356:396 Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. 36266488 6 27 from inactivation 1320:1331 arg1 growth 1379:1384 tumour growth 1372:1384 tumour growth 1372:1384 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 1 28 theme normal 219:224 arg1 cells 226:230 normal cells 219:230 normal cells 219:230 Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. 36266488 4 29 theme S170 931:934 arg1 phosphorylation 936:950 FBP1 S170 phosphorylation 926:950 FBP1 S170 phosphorylation 926:950 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 0 30 theme tumour 149:154 arg1 growth 156:161 tumour growth 149:161 tumour growth 149:161 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 30 theme tumour 149:154 arg1 Fructose-1,6-bisphosphatase 0:26 Fructose-1,6-bisphosphatase 1 0:28 Fructose-1,6-bisphosphatase 1 0:28 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 30 theme tumour 149:154 arg1 phosphatase 53:63 a protein phosphatase 43:63 a protein phosphatase 43:63 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 30 theme tumour 149:154 arg1 transcription 131:143 PPARα-regulated gene transcription 110:143 PPARα-regulated gene transcription 110:143 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 4 31 from transferase 854:864 arg1 cells 894:898 hepatocellular carcinoma cells 869:898 hepatocellular carcinoma cells 869:898 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 4 32 theme carcinoma 884:892 arg1 cells 894:898 hepatocellular carcinoma cells 869:898 hepatocellular carcinoma cells 869:898 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 5 33 theme carcinoma 1113:1121 arg1 specimens 1123:1131 hepatocellular carcinoma specimens 1098:1131 hepatocellular carcinoma specimens 1098:1131 In addition, FBP1 S170 phosphorylation inversely correlates with β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. 36266488 6 34 theme gene 1222:1225 arg1 regulation 1227:1236 gene regulation 1222:1236 gene regulation 1222:1236 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 2 35 theme FBP1 498:501 arg1 tetramer 503:510 the FBP1 tetramer 494:510 the FBP1 tetramer to monomers 494:522 Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. 36266488 5 36 theme patient 1137:1143 arg1 duration 1154:1161 patient survival duration 1137:1161 patient survival duration 1137:1161 In addition, FBP1 S170 phosphorylation inversely correlates with β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. 36266488 3 37 theme gene 750:753 arg1 expression 755:764 PPARα-mediated β-oxidation gene expression 723:764 PPARα-mediated β-oxidation gene expression 723:764 Importantly, nuclear FBP1 binds PPARα and functions as a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated β-oxidation gene expression. 36266488 2 38 theme PERK-mediated 406:418 arg1 phosphorylation 462:476 PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation 406:476 PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation 406:476 Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. 36266488 5 39 theme FBP1 1015:1018 arg1 phosphorylation 1025:1039 FBP1 S170 phosphorylation 1015:1039 FBP1 S170 phosphorylation 1015:1039 In addition, FBP1 S170 phosphorylation inversely correlates with β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. 36266488 0 40 theme protein 45:51 arg1 growth 156:161 tumour growth 149:161 tumour growth 149:161 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 40 theme protein 45:51 arg1 Fructose-1,6-bisphosphatase 0:26 Fructose-1,6-bisphosphatase 1 0:28 Fructose-1,6-bisphosphatase 1 0:28 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 40 theme protein 45:51 arg1 phosphatase 53:63 a protein phosphatase 43:63 a protein phosphatase 43:63 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 0 40 theme protein 45:51 arg1 transcription 131:143 PPARα-regulated gene transcription 110:143 PPARα-regulated gene transcription 110:143 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 6 41 theme FBP1 1214:1217 arg1 role 1206:1209 the differential role 1189:1209 the differential role of FBP1 in gene regulation in normal and tumour cells 1189:1263 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 3 42 theme PPARα-mediated 723:736 arg1 expression 755:764 PPARα-mediated β-oxidation gene expression 723:764 PPARα-mediated β-oxidation gene expression 723:764 Importantly, nuclear FBP1 binds PPARα and functions as a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated β-oxidation gene expression. 36266488 4 43 theme phosphorylation 936:950 arg1 inhibition 912:921 inhibition 912:921 inhibition of FBP1 S170 phosphorylation 912:950 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 4 43 theme phosphorylation 936:950 arg1 enhancement 956:966 enhancement 956:966 enhancement of β-oxidation for tumour growth 956:999 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 1 44 theme selective 244:252 arg1 advantages 254:263 selective advantages 244:263 selective advantages for survival and proliferation with unclearly defined mechanisms 244:328 Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. 36266488 3 45 theme β-oxidation 738:748 arg1 expression 755:764 PPARα-mediated β-oxidation gene expression 723:764 PPARα-mediated β-oxidation gene expression 723:764 Importantly, nuclear FBP1 binds PPARα and functions as a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated β-oxidation gene expression. 36266488 3 46 theme protein 652:658 arg1 phosphatase 660:670 a protein phosphatase 650:670 a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated β-oxidation gene expression 650:764 Importantly, nuclear FBP1 binds PPARα and functions as a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated β-oxidation gene expression. 36266488 3 46 theme protein 652:658 arg1 FBP1 616:619 nuclear FBP1 608:619 nuclear FBP1 608:619 Importantly, nuclear FBP1 binds PPARα and functions as a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated β-oxidation gene expression. 36266488 6 47 theme direct 1273:1278 arg1 modulation 1290:1299 direct chromatin modulation 1273:1299 direct chromatin modulation 1273:1299 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 4 48 theme overexpressed 811:823 arg1 transferase 854:864 overexpressed O-linked N-acetylglucosamine transferase 811:864 overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells 811:898 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 4 49 theme β-oxidation 971:981 arg1 inhibition 912:921 inhibition 912:921 inhibition of FBP1 S170 phosphorylation 912:950 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 4 49 theme β-oxidation 971:981 arg1 enhancement 956:966 enhancement 956:966 enhancement of β-oxidation for tumour growth 956:999 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 1 50 with proliferation 282:294 arg1 mechanisms 319:328 unclearly defined mechanisms 301:328 unclearly defined mechanisms 301:328 Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. 36266488 5 51 theme β-oxidation 1067:1077 arg1 expression 1084:1093 β-oxidation gene expression 1067:1093 β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration 1067:1161 In addition, FBP1 S170 phosphorylation inversely correlates with β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. 36266488 6 52 theme tumour 1372:1377 arg1 growth 1379:1384 tumour growth 1372:1384 tumour growth 1372:1384 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 1 53 contain possess 236:242 arg1 cells 171:175 Tumour cells 164:175 Tumour cells 164:175 Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. 36266488 1 53 contain possess 236:242 arg2 advantages 254:263 selective advantages 244:263 selective advantages for survival and proliferation with unclearly defined mechanisms 244:328 Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. 36266488 6 54 theme differential 1193:1204 arg1 role 1206:1209 the differential role 1189:1209 the differential role of FBP1 in gene regulation in normal and tumour cells 1189:1263 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 2 55 theme normal 379:384 arg1 hepatocytes 386:396 normal hepatocytes 379:396 normal hepatocytes 379:396 Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. 36266488 5 56 theme hepatocellular 1098:1111 arg1 carcinoma 1113:1121 hepatocellular carcinoma 1098:1121 hepatocellular carcinoma specimens 1098:1131 In addition, FBP1 S170 phosphorylation inversely correlates with β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. 36266488 6 57 theme protein 1340:1346 arg1 function 1360:1367 its protein phosphatase function 1336:1367 its protein phosphatase function 1336:1367 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 1 58 with survival 269:276 arg1 mechanisms 319:328 unclearly defined mechanisms 301:328 unclearly defined mechanisms 301:328 Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. 36266488 4 59 theme O-linked 825:832 arg1 transferase 854:864 overexpressed O-linked N-acetylglucosamine transferase 811:864 overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells 811:898 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 5 60 from expression 1084:1093 arg1 duration 1154:1161 patient survival duration 1137:1161 patient survival duration 1137:1161 In addition, FBP1 S170 phosphorylation inversely correlates with β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. 36266488 5 60 from expression 1084:1093 arg1 specimens 1123:1131 hepatocellular carcinoma specimens 1098:1131 hepatocellular carcinoma specimens 1098:1131 In addition, FBP1 S170 phosphorylation inversely correlates with β-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. 36266488 4 61 theme N-acetylglucosamine 834:852 arg1 transferase 854:864 overexpressed O-linked N-acetylglucosamine transferase 811:864 overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells 811:898 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 0 62 theme histone 84:90 arg1 H3 92:93 histone H3 84:93 histone H3 84:93 Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. 36266488 3 63 theme histone 694:700 arg1 H3T11 702:706 histone H3T11 694:706 histone H3T11 694:706 Importantly, nuclear FBP1 binds PPARα and functions as a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated β-oxidation gene expression. 36266488 1 64 theme Tumour 164:169 arg1 cells 171:175 Tumour cells 164:175 Tumour cells 164:175 Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. 36266488 6 65 theme phosphatase 1348:1358 arg1 function 1360:1367 its protein phosphatase function 1336:1367 its protein phosphatase function 1336:1367 These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth. 36266488 4 66 theme FBP1 926:929 arg1 phosphorylation 936:950 FBP1 S170 phosphorylation 926:950 FBP1 S170 phosphorylation 926:950 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 4 67 theme FBP1 780:783 arg1 S124 785:788 FBP1 S124 780:788 FBP1 S124 780:788 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 36266488 4 68 from O-GlcNAcylated 793:806 arg1 contrast 770:777 contrast 770:777 contrast 770:777 In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of β-oxidation for tumour growth. 35887161 6 0 theme pyruvate 1375:1382 arg1 activities 1477:1486 intermediate metabolic enzyme activities 1447:1486 intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle 1447:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 0 theme pyruvate 1375:1382 arg1 potential 1420:1428 mitochondrial membrane potential 1397:1428 mitochondrial membrane potential 1397:1428 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 0 theme pyruvate 1375:1382 arg1 contents 1363:1370 metabolite contents 1352:1370 metabolite contents of pyruvate and lactate 1352:1394 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 0 theme pyruvate 1375:1382 arg1 activities 1306:1315 Glycolytic enzyme activities 1288:1315 Glycolytic enzyme activities of hexokinase and pyruvate kinase 1288:1349 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 0 theme pyruvate 1375:1382 arg1 levels 1435:1440 ATP levels 1431:1440 ATP levels 1431:1440 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 3 1 theme granulosa 545:553 arg1 cells 555:559 bovine granulosa cells 538:559 bovine granulosa cells 538:559 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 1 2 theme processes 271:279 arg1 charge 239:244 charge 239:244 charge of almost all biological processes examined 239:288 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 4 3 theme elevated 944:951 arg1 expression 965:974 elevated OGA protein expression 944:974 elevated OGA protein expression 944:974 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 4 4 theme Pharmacological 633:647 arg1 inhibition 649:658 Pharmacological inhibition 633:658 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) 633:727 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 2 5 theme little 300:305 arg1 information 307:317 little information 300:317 little information 300:317 However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. 35887161 4 6 theme cellular 746:753 arg1 levels 764:769 decreased cellular O-GlcNAc levels 736:769 decreased cellular O-GlcNAc levels 736:769 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 6 7 theme pyruvate 1335:1342 arg1 kinase 1344:1349 pyruvate kinase 1335:1349 pyruvate kinase 1335:1349 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 1 8 theme post-translational 194:211 arg1 modification 133:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 1 8 theme post-translational 194:211 arg1 modification 213:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 4 9 theme OGT 990:992 arg1 expression 1002:1011 decreased OGT protein expression 980:1011 decreased OGT protein expression 980:1011 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 6 10 theme ATP 1431:1433 arg1 levels 1435:1440 ATP levels 1431:1440 ATP levels 1431:1440 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 4 11 from expression 1002:1011 arg1 cells 1026:1030 granulosa cells 1016:1030 granulosa cells 1016:1030 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 6 12 theme altered 1625:1631 arg1 levels 1642:1647 altered O-GlcNAc levels 1625:1647 altered O-GlcNAc levels 1625:1647 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 4 13 theme protein 957:963 arg1 expression 965:974 elevated OGA protein expression 944:974 elevated OGA protein expression 944:974 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 6 14 theme mitochondrial 1397:1409 arg1 potential 1420:1428 mitochondrial membrane potential 1397:1428 mitochondrial membrane potential 1397:1428 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 5 15 theme CDC42 1136:1140 arg1 transcripts 1151:1161 CDC42 and PCNA transcripts 1136:1161 CDC42 and PCNA transcripts 1136:1161 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 4 16 with inhibition 649:658 arg1 BADGP 722:726 BADGP 722:726 BADGP 722:726 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 4 16 with inhibition 649:658 arg1 benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside 672:719 benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside 672:719 benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) 672:727 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 7 17 theme protein 1750:1756 arg1 level 1717:1721 the expression level 1702:1721 the expression level of thioredoxin-interacting protein (TXNIP) 1702:1764 Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. 35887161 6 18 theme enzyme 1299:1304 arg1 activities 1306:1315 Glycolytic enzyme activities 1288:1315 Glycolytic enzyme activities of hexokinase and pyruvate kinase 1288:1349 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 19 theme lactate 1388:1394 arg1 activities 1477:1486 intermediate metabolic enzyme activities 1447:1486 intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle 1447:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 19 theme lactate 1388:1394 arg1 potential 1420:1428 mitochondrial membrane potential 1397:1428 mitochondrial membrane potential 1397:1428 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 19 theme lactate 1388:1394 arg1 contents 1363:1370 metabolite contents 1352:1370 metabolite contents of pyruvate and lactate 1352:1394 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 19 theme lactate 1388:1394 arg1 activities 1306:1315 Glycolytic enzyme activities 1288:1315 Glycolytic enzyme activities of hexokinase and pyruvate kinase 1288:1349 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 19 theme lactate 1388:1394 arg1 levels 1435:1440 ATP levels 1431:1440 ATP levels 1431:1440 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 5 20 theme PCNA 1146:1149 arg1 transcripts 1151:1161 CDC42 and PCNA transcripts 1136:1161 CDC42 and PCNA transcripts 1136:1161 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 8 21 theme granulosa 1901:1909 arg1 function 1916:1923 granulosa cell function 1901:1923 granulosa cell function 1901:1923 Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism. 35887161 5 22 theme CASPASE-3 1211:1219 arg1 genes 1194:1198 the pro-apoptotic genes 1176:1198 the pro-apoptotic genes of BAX and CASPASE-3 mRNA 1176:1224 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 5 22 theme CASPASE-3 1211:1219 arg1 ratio 1234:1238 the ratio 1230:1238 the ratio of BAX/BCL-2 1230:1251 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 7 23 theme expression 1706:1715 arg1 level 1717:1721 the expression level 1702:1721 the expression level of thioredoxin-interacting protein (TXNIP) 1702:1764 Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. 35887161 6 24 theme enzyme 1470:1475 arg1 activities 1477:1486 intermediate metabolic enzyme activities 1447:1486 intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle 1447:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 8 25 theme glucose 1929:1935 arg1 metabolism 1937:1946 glucose metabolism 1929:1946 glucose metabolism 1929:1946 Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism. 35887161 4 26 theme granulosa 1016:1024 arg1 cells 1026:1030 granulosa cells 1016:1030 granulosa cells 1016:1030 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 6 27 theme intermediate 1447:1458 arg1 activities 1477:1486 intermediate metabolic enzyme activities 1447:1486 intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle 1447:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 5 28 theme O-GlcNAc 1046:1053 arg1 cycling 1055:1061 Dysregulated O-GlcNAc cycling 1033:1061 Dysregulated O-GlcNAc cycling 1033:1061 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 7 29 theme OGT 1674:1676 arg1 inhibition 1660:1669 inhibition 1660:1669 inhibition of OGT 1660:1676 Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. 35887161 5 30 theme BAX 1203:1205 arg1 genes 1194:1198 the pro-apoptotic genes 1176:1198 the pro-apoptotic genes of BAX and CASPASE-3 mRNA 1176:1224 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 5 30 theme BAX 1203:1205 arg1 ratio 1234:1238 the ratio 1230:1238 the ratio of BAX/BCL-2 1230:1251 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 0 31 theme Ovarian 50:56 arg1 Injury 73:78 Ovarian Granulosa Cell Injury 50:78 Ovarian Granulosa Cell Injury 50:78 Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine. 35887161 4 32 theme protein 795:801 arg1 expressions 803:813 OGA protein expressions 791:813 OGA protein expressions 791:813 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 2 33 theme glucose 417:423 arg1 metabolism 425:434 glucose metabolism 417:434 glucose metabolism 417:434 However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. 35887161 1 34 theme β-N-acetylglucosamine 100:120 arg1 modification 133:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 1 34 theme β-N-acetylglucosamine 100:120 arg1 modification 213:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 0 35 theme O-GlcNAcylation 14:28 arg1 Homeostasis 30:40 O-GlcNAcylation Homeostasis 14:40 O-GlcNAcylation Homeostasis 14:40 Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine. 35887161 1 36 theme O-GlcNAc 123:130 arg1 modification 133:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 1 36 theme O-GlcNAc 123:130 arg1 modification 213:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 3 37 theme O-GlcNAc 483:490 arg1 cycling 492:498 disrupted O-GlcNAc cycling 473:498 disrupted O-GlcNAc cycling 473:498 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 6 38 theme malate 1519:1524 arg1 dehydrogenase 1526:1538 malate dehydrogenase 1519:1538 malate dehydrogenase 1519:1538 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 5 39 theme proliferation-related 1105:1125 arg1 genes 1127:1131 the proliferation-related genes 1101:1131 the proliferation-related genes of CDC42 and PCNA transcripts 1101:1161 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 2 40 theme O-GlcNAcylation 370:384 arg1 regulation 356:365 the molecular regulation 342:365 the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism 342:434 However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. 35887161 6 41 theme dehydrogenase 1501:1513 arg1 activities 1477:1486 intermediate metabolic enzyme activities 1447:1486 intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle 1447:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 41 theme dehydrogenase 1501:1513 arg1 potential 1420:1428 mitochondrial membrane potential 1397:1428 mitochondrial membrane potential 1397:1428 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 41 theme dehydrogenase 1501:1513 arg1 contents 1363:1370 metabolite contents 1352:1370 metabolite contents of pyruvate and lactate 1352:1394 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 41 theme dehydrogenase 1501:1513 arg1 activities 1306:1315 Glycolytic enzyme activities 1288:1315 Glycolytic enzyme activities of hexokinase and pyruvate kinase 1288:1349 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 41 theme dehydrogenase 1501:1513 arg1 levels 1435:1440 ATP levels 1431:1440 ATP levels 1431:1440 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 5 42 theme BAX/BCL-2 1243:1251 arg1 genes 1194:1198 the pro-apoptotic genes 1176:1198 the pro-apoptotic genes of BAX and CASPASE-3 mRNA 1176:1224 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 5 42 theme BAX/BCL-2 1243:1251 arg1 ratio 1234:1238 the ratio 1230:1238 the ratio of BAX/BCL-2 1230:1251 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 3 43 from impact 463:468 arg1 apoptosis 525:533 apoptosis 525:533 apoptosis 525:533 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 3 43 from impact 463:468 arg1 proliferation 507:519 proliferation 507:519 proliferation 507:519 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 3 44 theme cells 555:559 arg1 apoptosis 525:533 apoptosis 525:533 apoptosis 525:533 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 3 44 theme cells 555:559 arg1 proliferation 507:519 proliferation 507:519 proliferation 507:519 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 4 45 theme OGT 663:665 arg1 inhibition 649:658 Pharmacological inhibition 633:658 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) 633:727 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 1 46 link O-linked 91:98 arg1 modification 133:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 1 46 link O-linked 91:98 arg1 modification 213:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 2 47 theme granulosa 389:397 arg1 function 404:411 granulosa cell function 389:411 granulosa cell function 389:411 However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. 35887161 1 48 theme biological 260:269 arg1 processes 271:279 almost all biological processes 249:279 almost all biological processes examined 249:288 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 2 49 from regulation 356:365 arg1 metabolism 425:434 glucose metabolism 417:434 glucose metabolism 417:434 However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. 35887161 2 49 from regulation 356:365 arg1 function 404:411 granulosa cell function 389:411 granulosa cell function 389:411 However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. 35887161 6 50 theme acid 1570:1573 arg1 cycle 1575:1579 the tricarboxylic acid cycle 1552:1579 the tricarboxylic acid cycle 1552:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 51 theme metabolite 1352:1361 arg1 contents 1363:1370 metabolite contents 1352:1370 metabolite contents of pyruvate and lactate 1352:1394 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 0 52 theme Granulosa 58:66 arg1 Injury 73:78 Ovarian Granulosa Cell Injury 50:78 Ovarian Granulosa Cell Injury 50:78 Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine. 35887161 8 53 contain has 1876:1878 arg2 effect 1891:1896 a profound effect 1880:1896 a profound effect 1880:1896 Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism. 35887161 8 53 contain has 1876:1878 arg1 perturbation 1843:1854 perturbation 1843:1854 perturbation of O-GlcNAc cycling 1843:1874 Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism. 35887161 6 54 theme kinase 1344:1349 arg1 activities 1477:1486 intermediate metabolic enzyme activities 1447:1486 intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle 1447:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 54 theme kinase 1344:1349 arg1 potential 1420:1428 mitochondrial membrane potential 1397:1428 mitochondrial membrane potential 1397:1428 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 54 theme kinase 1344:1349 arg1 contents 1363:1370 metabolite contents 1352:1370 metabolite contents of pyruvate and lactate 1352:1394 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 54 theme kinase 1344:1349 arg1 activities 1306:1315 Glycolytic enzyme activities 1288:1315 Glycolytic enzyme activities of hexokinase and pyruvate kinase 1288:1349 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 54 theme kinase 1344:1349 arg1 levels 1435:1440 ATP levels 1431:1440 ATP levels 1431:1440 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 1 55 theme dynamic 186:192 arg1 modification 133:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 1 55 theme dynamic 186:192 arg1 modification 213:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 4 56 theme decreased 736:744 arg1 levels 764:769 decreased cellular O-GlcNAc levels 736:769 decreased cellular O-GlcNAc levels 736:769 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 6 57 theme O-GlcNAc 1633:1640 arg1 levels 1642:1647 altered O-GlcNAc levels 1625:1647 altered O-GlcNAc levels 1625:1647 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 5 58 theme Dysregulated 1033:1044 arg1 cycling 1055:1061 Dysregulated O-GlcNAc cycling 1033:1061 Dysregulated O-GlcNAc cycling 1033:1061 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 4 59 theme decreased 980:988 arg1 expression 1002:1011 decreased OGT protein expression 980:1011 decreased OGT protein expression 980:1011 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 3 60 theme bovine 538:543 arg1 cells 555:559 bovine granulosa cells 538:559 bovine granulosa cells 538:559 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 8 61 theme O-GlcNAc 1859:1866 arg1 cycling 1868:1874 O-GlcNAc cycling 1859:1874 O-GlcNAc cycling 1859:1874 Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism. 35887161 4 62 theme protein 994:1000 arg1 expression 1002:1011 decreased OGT protein expression 980:1011 decreased OGT protein expression 980:1011 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 6 63 theme hexokinase 1320:1329 arg1 activities 1477:1486 intermediate metabolic enzyme activities 1447:1486 intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle 1447:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 63 theme hexokinase 1320:1329 arg1 potential 1420:1428 mitochondrial membrane potential 1397:1428 mitochondrial membrane potential 1397:1428 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 63 theme hexokinase 1320:1329 arg1 contents 1363:1370 metabolite contents 1352:1370 metabolite contents of pyruvate and lactate 1352:1394 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 63 theme hexokinase 1320:1329 arg1 activities 1306:1315 Glycolytic enzyme activities 1288:1315 Glycolytic enzyme activities of hexokinase and pyruvate kinase 1288:1349 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 63 theme hexokinase 1320:1329 arg1 levels 1435:1440 ATP levels 1431:1440 ATP levels 1431:1440 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 64 theme membrane 1411:1418 arg1 potential 1420:1428 mitochondrial membrane potential 1397:1428 mitochondrial membrane potential 1397:1428 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 5 65 theme pro-apoptotic 1180:1192 arg1 genes 1194:1198 the pro-apoptotic genes 1176:1198 the pro-apoptotic genes of BAX and CASPASE-3 mRNA 1176:1224 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 3 66 theme glucose 613:619 arg1 metabolism 621:630 glucose metabolism 613:630 glucose metabolism 613:630 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 7 67 theme thioredoxin-interacting 1726:1748 arg1 TXNIP 1759:1763 TXNIP 1759:1763 TXNIP 1759:1763 Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. 35887161 7 67 theme thioredoxin-interacting 1726:1748 arg1 protein 1750:1756 thioredoxin-interacting protein 1726:1756 thioredoxin-interacting protein (TXNIP) 1726:1764 Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. 35887161 4 68 theme OGA 953:955 arg1 expression 965:974 elevated OGA protein expression 944:974 elevated OGA protein expression 944:974 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 4 69 from expression 965:974 arg1 cells 1026:1030 granulosa cells 1016:1030 granulosa cells 1016:1030 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 8 70 theme profound 1882:1889 arg1 effect 1891:1896 a profound effect 1880:1896 a profound effect 1880:1896 Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism. 35887161 6 71 theme Glycolytic 1288:1297 arg1 activities 1306:1315 Glycolytic enzyme activities 1288:1315 Glycolytic enzyme activities of hexokinase and pyruvate kinase 1288:1349 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 72 theme succinate 1491:1499 arg1 dehydrogenase 1501:1513 succinate dehydrogenase 1491:1513 succinate dehydrogenase 1491:1513 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 5 73 theme transcripts 1151:1161 arg1 genes 1127:1131 the proliferation-related genes 1101:1131 the proliferation-related genes of CDC42 and PCNA transcripts 1101:1161 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 1 74 theme ubiquitous 151:160 arg1 modification 133:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 1 74 theme ubiquitous 151:160 arg1 modification 213:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 4 75 theme O-GlcNAc 755:762 arg1 levels 764:769 decreased cellular O-GlcNAc levels 736:769 decreased cellular O-GlcNAc levels 736:769 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 8 76 theme cell 1911:1914 arg1 function 1916:1923 granulosa cell function 1901:1923 granulosa cell function 1901:1923 Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism. 35887161 1 77 theme reversible 163:172 arg1 modification 133:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 1 77 theme reversible 163:172 arg1 modification 213:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 6 78 theme metabolic 1460:1468 arg1 activities 1477:1486 intermediate metabolic enzyme activities 1447:1486 intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle 1447:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 3 79 dep proliferation 507:519 arg1 the 503:505 the 503:505 the 503:505 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 8 80 theme cycling 1868:1874 arg1 perturbation 1843:1854 perturbation 1843:1854 perturbation of O-GlcNAc cycling 1843:1874 Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism. 35887161 4 81 theme O-GlcNAc 835:842 arg1 levels 844:849 O-GlcNAc levels 835:849 O-GlcNAc levels 835:849 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 3 82 theme disrupted 473:481 arg1 cycling 492:498 disrupted O-GlcNAc cycling 473:498 disrupted O-GlcNAc cycling 473:498 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 6 83 theme tricarboxylic 1556:1568 arg1 cycle 1575:1579 the tricarboxylic acid cycle 1552:1579 the tricarboxylic acid cycle 1552:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 1 84 theme O-linked 91:98 arg1 modification 133:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 91:144 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 1 84 theme O-linked 91:98 arg1 modification 213:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 a ubiquitous, reversible, and highly dynamic post-translational modification 149:224 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 35887161 4 85 theme OGA 791:793 arg1 expressions 803:813 OGA protein expressions 791:813 OGA protein expressions 791:813 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 0 86 theme Homeostasis 30:40 arg1 Disruption 0:9 Disruption 0:9 Disruption of O-GlcNAcylation Homeostasis 0:40 Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine. 35887161 6 87 theme dehydrogenase 1526:1538 arg1 activities 1477:1486 intermediate metabolic enzyme activities 1447:1486 intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle 1447:1579 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 87 theme dehydrogenase 1526:1538 arg1 potential 1420:1428 mitochondrial membrane potential 1397:1428 mitochondrial membrane potential 1397:1428 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 87 theme dehydrogenase 1526:1538 arg1 contents 1363:1370 metabolite contents 1352:1370 metabolite contents of pyruvate and lactate 1352:1394 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 87 theme dehydrogenase 1526:1538 arg1 activities 1306:1315 Glycolytic enzyme activities 1288:1315 Glycolytic enzyme activities of hexokinase and pyruvate kinase 1288:1349 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 6 87 theme dehydrogenase 1526:1538 arg1 levels 1435:1440 ATP levels 1431:1440 ATP levels 1431:1440 Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. 35887161 5 88 theme apoptotic 1272:1280 arg1 rate 1282:1285 the apoptotic rate 1268:1285 the apoptotic rate 1268:1285 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 7 89 theme OGA 1785:1787 arg1 repression 1771:1780 repression 1771:1780 repression of OGA 1771:1787 Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. 35887161 5 90 dep BAX 1203:1205 arg1 mRNA 1221:1224 mRNA 1221:1224 mRNA 1221:1224 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 3 91 theme cycling 492:498 arg1 impact 463:468 the impact 459:468 the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells 459:559 This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. 35887161 0 92 theme Cell 68:71 arg1 Injury 73:78 Ovarian Granulosa Cell Injury 50:78 Ovarian Granulosa Cell Injury 50:78 Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine. 35887161 7 93 contain had 1789:1791 arg2 effect 1796:1801 no effect 1793:1801 no effect 1793:1801 Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. 35887161 7 93 contain had 1789:1791 arg1 repression 1771:1780 repression 1771:1780 repression of OGA 1771:1787 Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. 35887161 5 94 theme cell 1071:1074 arg1 viability 1076:1084 cell viability 1071:1084 cell viability 1071:1084 Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. 35887161 2 95 theme molecular 346:354 arg1 regulation 356:365 the molecular regulation 342:365 the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism 342:434 However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. 35887161 4 96 theme OGA 860:862 arg1 O- 875:876 O- 875:876 O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc) 875:929 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 4 96 theme OGA 860:862 arg1 inhibitor 864:872 the OGA inhibitor 856:872 the OGA inhibitor 856:872 Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. 35887161 2 97 theme cell 399:402 arg1 function 404:411 granulosa cell function 389:411 granulosa cell function 389:411 However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. 35887161 1 98 theme all 256:258 arg1 processes 271:279 almost all biological processes 249:279 almost all biological processes examined 249:288 O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. 37067567 3 0 theme Reciprocal 520:529 arg1 modification 598:609 a dynamic modification 588:609 a dynamic modification in cytoplasmic proteins 588:633 Reciprocal crosstalk between O-GlcNAcylation and phosphorylation is a dynamic modification in cytoplasmic proteins. 37067567 3 0 theme Reciprocal 520:529 arg1 crosstalk 531:539 Reciprocal crosstalk 520:539 Reciprocal crosstalk between O-GlcNAcylation and phosphorylation 520:583 Reciprocal crosstalk between O-GlcNAcylation and phosphorylation is a dynamic modification in cytoplasmic proteins. 37067567 1 1 theme many 257:260 arg1 processes 273:281 many biological processes 257:281 many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity 257:397 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 7 2 gly glycosylated 1235:1246 arg1 sites 1248:1252 these glycosylated sites 1229:1252 these glycosylated sites 1229:1252 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 3 theme glycosylated 1235:1246 arg1 sites 1248:1252 these glycosylated sites 1229:1252 these glycosylated sites 1229:1252 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 0 4 theme In 0:1 arg1 analysis 10:17 In silico analysis 0:17 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 0:148 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 4 5 theme other 717:721 arg1 molecules 723:731 other molecules 717:731 other molecules 717:731 It modulates the functions of the proteins by regulating their interactions with other molecules in response to the continuously changeable cell microenvironment. 37067567 1 6 from processes 273:281 arg1 system 298:303 the nervous system 286:303 the nervous system 286:303 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 5 7 theme human 969:973 arg1 sequence 980:987 human Dab1 sequence 969:987 human Dab1 sequence 969:987 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 4 8 theme proteins 670:677 arg1 functions 653:661 the functions 649:661 the functions of the proteins 649:677 It modulates the functions of the proteins by regulating their interactions with other molecules in response to the continuously changeable cell microenvironment. 37067567 7 9 theme twenty-one 1206:1215 arg1 residues 1217:1224 Conserved twenty-one residues 1196:1224 Conserved twenty-one residues of these glycosylated sites 1196:1252 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 9 theme twenty-one 1206:1215 arg1 sites 1248:1252 these glycosylated sites 1229:1252 these glycosylated sites 1229:1252 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 3 10 theme dynamic 590:596 arg1 crosstalk 531:539 Reciprocal crosstalk 520:539 Reciprocal crosstalk between O-GlcNAcylation and phosphorylation 520:583 Reciprocal crosstalk between O-GlcNAcylation and phosphorylation is a dynamic modification in cytoplasmic proteins. 37067567 3 10 theme dynamic 590:596 arg1 modification 598:609 a dynamic modification 588:609 a dynamic modification in cytoplasmic proteins 588:633 Reciprocal crosstalk between O-GlcNAcylation and phosphorylation is a dynamic modification in cytoplasmic proteins. 37067567 9 11 theme coil 1549:1552 arg1 structures 1554:1563 coil structures 1549:1563 coil structures as well as α-helix and β-strands 1549:1596 Dab1 protein models were frequently composed of coil structures as well as α-helix and β-strands. 37067567 1 12 theme essential 195:203 arg1 functions 205:213 essential functions 195:213 essential functions regulated by reelin signaling 195:243 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 10 13 theme coil 1707:1710 arg1 region 1712:1717 the coil region 1703:1717 the coil region of the protein model 1703:1738 Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. 37067567 5 14 theme crosstalk 1007:1015 arg1 sites 960:964 the O-β-GlcNAcylation and phosphorylation sites 918:964 sites 960:964 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 14 theme crosstalk 1007:1015 arg1 crosstalk 1007:1015 their reciprocal crosstalk 990:1015 their reciprocal crosstalk 990:1015 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 14 theme crosstalk 1007:1015 arg1 kinases 1032:1038 potential kinases 1022:1038 potential kinases catalyzing the phosphorylation 1022:1069 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 14 theme crosstalk 1007:1015 arg1 sequence 980:987 human Dab1 sequence 969:987 human Dab1 sequence 969:987 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 7 15 theme various 1284:1290 arg1 GSK3 1328:1331 GSK3 1328:1331 GSK3 1328:1331 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 15 theme various 1284:1290 arg1 RSK 1344:1346 RSK 1344:1346 RSK 1344:1346 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 15 theme various 1284:1290 arg1 ATM 1311:1313 ATM 1311:1313 ATM 1311:1313 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 15 theme various 1284:1290 arg1 p38MAPK 1365:1371 p38MAPK 1365:1371 p38MAPK 1365:1371 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 15 theme various 1284:1290 arg1 cdc2 1349:1352 cdc2 1349:1352 cdc2 1349:1352 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 15 theme various 1284:1290 arg1 CKI 1316:1318 CKI 1316:1318 CKI 1316:1318 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 15 theme various 1284:1290 arg1 PKC 1334:1336 PKC 1334:1336 PKC 1334:1336 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 15 theme various 1284:1290 arg1 PKG 1339:1341 PKG 1339:1341 PKG 1339:1341 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 15 theme various 1284:1290 arg1 kinases 1292:1298 various kinases 1284:1298 various kinases 1284:1298 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 15 theme various 1284:1290 arg1 cdk5 1355:1358 cdk5 1355:1358 cdk5 1355:1358 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 15 theme various 1284:1290 arg1 DNAPK 1321:1325 DNAPK 1321:1325 DNAPK 1321:1325 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 4 16 theme cell 776:779 arg1 microenvironment 781:796 the continuously changeable cell microenvironment 748:796 the continuously changeable cell microenvironment 748:796 It modulates the functions of the proteins by regulating their interactions with other molecules in response to the continuously changeable cell microenvironment. 37067567 4 17 dep microenvironment 781:796 arg1 response 736:743 response 736:743 response 736:743 It modulates the functions of the proteins by regulating their interactions with other molecules in response to the continuously changeable cell microenvironment. 37067567 6 18 theme potential 1116:1124 arg1 O-β-GlcNAcylation 1139:1155 potential thirty-seven O-β-GlcNAcylation and sixty-seven phosphorylation sites 1116:1193 O-β-GlcNAcylation 1139:1155 In this study, we determined potential thirty-seven O-β-GlcNAcylation and sixty-seven phosphorylation sites. 37067567 0 19 from sites 98:102 arg1 vertebrates 137:147 vertebrates 137:147 vertebrates 137:147 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 5 20 theme conserved 822:830 arg1 sites 844:848 conserved recognition sites 822:848 conserved recognition sites for phosphorylation in their N-terminal protein interaction domain 822:915 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 1 21 theme cell 316:319 arg1 motility 321:328 cell motility 316:328 cell motility 316:328 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 5 22 theme sequence 980:987 arg1 sites 960:964 the O-β-GlcNAcylation and phosphorylation sites 918:964 sites 960:964 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 22 theme sequence 980:987 arg1 crosstalk 1007:1015 their reciprocal crosstalk 990:1015 their reciprocal crosstalk 990:1015 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 22 theme sequence 980:987 arg1 kinases 1032:1038 potential kinases 1022:1038 potential kinases catalyzing the phosphorylation 1022:1069 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 22 theme sequence 980:987 arg1 sequence 980:987 human Dab1 sequence 969:987 human Dab1 sequence 969:987 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 23 contain contains 813:820 arg2 sites 844:848 conserved recognition sites 822:848 conserved recognition sites for phosphorylation in their N-terminal protein interaction domain 822:915 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 23 contain contains 813:820 arg1 Dab1 808:811 Dab1 808:811 Dab1 808:811 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 11 24 theme signaling 1850:1858 arg1 process 1860:1866 the Dab1 signaling process 1841:1866 the Dab1 signaling process 1841:1866 These findings may guide biochemical, genetic, and glyco-biology based on further experiments about the Dab1 signaling process. 37067567 9 25 theme protein 1506:1512 arg1 models 1514:1519 Dab1 protein models 1501:1519 Dab1 protein models 1501:1519 Dab1 protein models were frequently composed of coil structures as well as α-helix and β-strands. 37067567 12 26 theme pathological 1982:1993 arg1 conditions 1995:2004 pathological conditions 1982:2004 pathological conditions in neurodegenerative diseases such as Alzheimer's disease 1982:2062 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 10 27 theme model 1734:1738 arg1 region 1712:1717 the coil region 1703:1717 the coil region of the protein model 1703:1738 Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. 37067567 5 28 theme protein 890:896 arg1 domain 910:915 their N-terminal protein interaction domain 873:915 their N-terminal protein interaction domain 873:915 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 1 29 theme biological 262:271 arg1 processes 273:281 many biological processes 257:281 many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity 257:397 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 5 30 theme kinases 1032:1038 arg1 sites 960:964 the O-β-GlcNAcylation and phosphorylation sites 918:964 sites 960:964 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 30 theme kinases 1032:1038 arg1 crosstalk 1007:1015 their reciprocal crosstalk 990:1015 their reciprocal crosstalk 990:1015 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 30 theme kinases 1032:1038 arg1 kinases 1032:1038 potential kinases 1022:1038 potential kinases catalyzing the phosphorylation 1022:1069 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 30 theme kinases 1032:1038 arg1 sequence 980:987 human Dab1 sequence 969:987 human Dab1 sequence 969:987 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 8 31 theme three-dimensional 1449:1465 arg1 structures 1467:1476 three-dimensional structures 1449:1476 three-dimensional structures 1449:1476 In addition, we analyzed these conserved sites at our constructed two- and three-dimensional structures of human Dab1 protein. 37067567 12 32 theme process 1956:1962 arg1 treatment 1968:1976 treatment 1968:1976 treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease 1968:2062 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 12 32 theme process 1956:1962 arg1 view 1929:1932 view 1929:1932 view of the Dab1 signaling process 1929:1962 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 6 33 theme sixty-seven 1161:1171 arg1 sites 1189:1193 potential thirty-seven O-β-GlcNAcylation and sixty-seven phosphorylation sites 1116:1193 sites 1189:1193 In this study, we determined potential thirty-seven O-β-GlcNAcylation and sixty-seven phosphorylation sites. 37067567 1 34 theme nervous 290:296 arg1 system 298:303 the nervous system 286:303 the nervous system 286:303 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 12 35 theme treatment 1968:1976 arg1 point 1920:1924 the point 1916:1924 the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease 1916:2062 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 2 36 theme cytoplasmic 460:470 arg1 proteins 472:479 cytoplasmic proteins 460:479 cytoplasmic proteins 460:479 Posttranslational modifications directly guide the fates of cytoplasmic proteins to complete their functions correctly. 37067567 0 37 theme O-linked 53:60 arg1 β-GlcNAcylation 62:76 O-linked β-GlcNAcylation 53:76 O-linked β-GlcNAcylation 53:76 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 8 38 theme Dab1 1487:1490 arg1 protein 1492:1498 human Dab1 protein 1481:1498 human Dab1 protein 1481:1498 In addition, we analyzed these conserved sites at our constructed two- and three-dimensional structures of human Dab1 protein. 37067567 1 39 with protein 182:188 arg1 functions 205:213 essential functions 195:213 essential functions regulated by reelin signaling 195:243 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 12 40 theme view 1929:1932 arg1 point 1920:1924 the point 1916:1924 the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease 1916:2062 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 11 41 theme further 1815:1821 arg1 experiments 1823:1833 further experiments 1815:1833 further experiments about the Dab1 signaling process 1815:1866 These findings may guide biochemical, genetic, and glyco-biology based on further experiments about the Dab1 signaling process. 37067567 12 42 theme Dab1 1941:1944 arg1 process 1956:1962 the Dab1 signaling process 1937:1962 the Dab1 signaling process 1937:1962 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 10 43 theme sites 1633:1637 arg1 sites 1633:1637 these conserved crosstalk sites 1607:1637 these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation 1607:1683 Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. 37067567 10 43 theme sites 1633:1637 arg1 Many 1599:1602 Many 1599:1602 Many 1599:1602 Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. 37067567 0 44 dep In 0:1 arg1 silico 3:8 silico 3:8 silico 3:8 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 10 45 theme conserved 1613:1621 arg1 sites 1633:1637 these conserved crosstalk sites 1607:1637 these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation 1607:1683 Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. 37067567 5 46 theme recognition 832:842 arg1 sites 844:848 conserved recognition sites 822:848 conserved recognition sites for phosphorylation in their N-terminal protein interaction domain 822:915 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 7 47 theme sites 1248:1252 arg1 residues 1217:1224 Conserved twenty-one residues 1196:1224 Conserved twenty-one residues of these glycosylated sites 1196:1252 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 47 theme sites 1248:1252 arg1 sites 1248:1252 these glycosylated sites 1229:1252 these glycosylated sites 1229:1252 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 9 48 theme Dab1 1501:1504 arg1 models 1514:1519 Dab1 protein models 1501:1519 Dab1 protein models 1501:1519 Dab1 protein models were frequently composed of coil structures as well as α-helix and β-strands. 37067567 5 49 theme phosphorylation 944:958 arg1 sites 960:964 the O-β-GlcNAcylation and phosphorylation sites 918:964 sites 960:964 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 49 theme phosphorylation 944:958 arg1 crosstalk 1007:1015 their reciprocal crosstalk 990:1015 their reciprocal crosstalk 990:1015 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 49 theme phosphorylation 944:958 arg1 kinases 1032:1038 potential kinases 1022:1038 potential kinases catalyzing the phosphorylation 1022:1069 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 49 theme phosphorylation 944:958 arg1 sequence 980:987 human Dab1 sequence 969:987 human Dab1 sequence 969:987 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 0 50 theme crosstalk 35:43 arg1 analysis 10:17 In silico analysis 0:17 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 0:148 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 0 51 theme protein 126:132 arg1 β-GlcNAcylation 62:76 O-linked β-GlcNAcylation 53:76 O-linked β-GlcNAcylation 53:76 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 0 51 theme protein 126:132 arg1 sites 98:102 phosphorylation sites 82:102 phosphorylation sites 82:102 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 0 51 theme protein 126:132 arg1 protein 126:132 Disabled 1 adaptor protein 107:132 Disabled 1 adaptor protein 107:132 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 1 52 theme adaptor 174:180 arg1 protein 182:188 an adaptor protein 171:188 an adaptor protein with essential functions regulated by reelin signaling 171:243 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 1 52 theme adaptor 174:180 arg1 1 159:159 1 159:159 1 159:159 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 5 53 theme O-β-GlcNAcylation 922:938 arg1 sites 960:964 the O-β-GlcNAcylation and phosphorylation sites 918:964 sites 960:964 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 53 theme O-β-GlcNAcylation 922:938 arg1 crosstalk 1007:1015 their reciprocal crosstalk 990:1015 their reciprocal crosstalk 990:1015 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 53 theme O-β-GlcNAcylation 922:938 arg1 kinases 1032:1038 potential kinases 1022:1038 potential kinases catalyzing the phosphorylation 1022:1069 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 5 53 theme O-β-GlcNAcylation 922:938 arg1 sequence 980:987 human Dab1 sequence 969:987 human Dab1 sequence 969:987 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 0 54 from β-GlcNAcylation 62:76 arg1 vertebrates 137:147 vertebrates 137:147 vertebrates 137:147 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 1 55 theme synaptic 379:386 arg1 plasticity 388:397 synaptic plasticity 379:397 synaptic plasticity 379:397 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 3 56 theme cytoplasmic 614:624 arg1 proteins 626:633 cytoplasmic proteins 614:633 cytoplasmic proteins 614:633 Reciprocal crosstalk between O-GlcNAcylation and phosphorylation is a dynamic modification in cytoplasmic proteins. 37067567 5 57 theme reciprocal 996:1005 arg1 crosstalk 1007:1015 their reciprocal crosstalk 990:1015 their reciprocal crosstalk 990:1015 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 7 58 theme Conserved 1196:1204 arg1 residues 1217:1224 Conserved twenty-one residues 1196:1224 Conserved twenty-one residues of these glycosylated sites 1196:1252 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 7 58 theme Conserved 1196:1204 arg1 sites 1248:1252 these glycosylated sites 1229:1252 these glycosylated sites 1229:1252 Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. 37067567 6 59 theme thirty-seven 1126:1137 arg1 O-β-GlcNAcylation 1139:1155 potential thirty-seven O-β-GlcNAcylation and sixty-seven phosphorylation sites 1116:1193 O-β-GlcNAcylation 1139:1155 In this study, we determined potential thirty-seven O-β-GlcNAcylation and sixty-seven phosphorylation sites. 37067567 4 60 theme changeable 765:774 arg1 microenvironment 781:796 the continuously changeable cell microenvironment 748:796 the continuously changeable cell microenvironment 748:796 It modulates the functions of the proteins by regulating their interactions with other molecules in response to the continuously changeable cell microenvironment. 37067567 3 61 from modification 598:609 arg1 proteins 626:633 cytoplasmic proteins 614:633 cytoplasmic proteins 614:633 Reciprocal crosstalk between O-GlcNAcylation and phosphorylation is a dynamic modification in cytoplasmic proteins. 37067567 11 62 theme Dab1 1845:1848 arg1 process 1860:1866 the Dab1 signaling process 1841:1866 the Dab1 signaling process 1841:1866 These findings may guide biochemical, genetic, and glyco-biology based on further experiments about the Dab1 signaling process. 37067567 5 63 theme Dab1 975:978 arg1 sequence 980:987 human Dab1 sequence 969:987 human Dab1 sequence 969:987 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 0 64 theme phosphorylation 82:96 arg1 protein 126:132 Disabled 1 adaptor protein 107:132 Disabled 1 adaptor protein 107:132 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 0 64 theme phosphorylation 82:96 arg1 sites 98:102 phosphorylation sites 82:102 phosphorylation sites 82:102 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 0 65 theme adaptor 118:124 arg1 protein 126:132 Disabled 1 adaptor protein 107:132 Disabled 1 adaptor protein 107:132 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 5 66 from phosphorylation 854:868 arg1 domain 910:915 their N-terminal protein interaction domain 873:915 their N-terminal protein interaction domain 873:915 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 12 67 from conditions 1995:2004 arg1 disease 2056:2062 Alzheimer's disease 2044:2062 Alzheimer's disease 2044:2062 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 12 67 from conditions 1995:2004 arg1 diseases 2027:2034 neurodegenerative diseases 2009:2034 neurodegenerative diseases such as Alzheimer's disease 2009:2062 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 8 68 theme conserved 1405:1413 arg1 sites 1415:1419 these conserved sites 1399:1419 these conserved sites 1399:1419 In addition, we analyzed these conserved sites at our constructed two- and three-dimensional structures of human Dab1 protein. 37067567 1 69 theme cortical 341:348 arg1 development 350:360 cortical development 341:360 cortical development 341:360 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 37067567 5 70 theme N-terminal 879:888 arg1 domain 910:915 their N-terminal protein interaction domain 873:915 their N-terminal protein interaction domain 873:915 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 12 71 theme neurodegenerative 2009:2025 arg1 disease 2056:2062 Alzheimer's disease 2044:2062 Alzheimer's disease 2044:2062 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 12 71 theme neurodegenerative 2009:2025 arg1 diseases 2027:2034 neurodegenerative diseases 2009:2034 neurodegenerative diseases such as Alzheimer's disease 2009:2062 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 5 72 theme potential 1022:1030 arg1 kinases 1032:1038 potential kinases 1022:1038 potential kinases catalyzing the phosphorylation 1022:1069 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 10 73 theme protein 1726:1732 arg1 model 1734:1738 the protein model 1722:1738 the protein model 1722:1738 Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. 37067567 5 74 theme interaction 898:908 arg1 domain 910:915 their N-terminal protein interaction domain 873:915 their N-terminal protein interaction domain 873:915 Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. 37067567 6 75 theme phosphorylation 1173:1187 arg1 sites 1189:1193 potential thirty-seven O-β-GlcNAcylation and sixty-seven phosphorylation sites 1116:1193 sites 1189:1193 In this study, we determined potential thirty-seven O-β-GlcNAcylation and sixty-seven phosphorylation sites. 37067567 2 76 theme Posttranslational 400:416 arg1 modifications 418:430 Posttranslational modifications 400:430 Posttranslational modifications 400:430 Posttranslational modifications directly guide the fates of cytoplasmic proteins to complete their functions correctly. 37067567 0 77 theme possible 26:33 arg1 crosstalk 35:43 the possible crosstalk 22:43 the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates 22:147 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 2 78 theme proteins 472:479 arg1 fates 451:455 the fates 447:455 the fates of cytoplasmic proteins 447:479 Posttranslational modifications directly guide the fates of cytoplasmic proteins to complete their functions correctly. 37067567 4 79 with interactions 699:710 arg1 molecules 723:731 other molecules 717:731 other molecules 717:731 It modulates the functions of the proteins by regulating their interactions with other molecules in response to the continuously changeable cell microenvironment. 37067567 0 80 theme Disabled 107:114 arg1 protein 126:132 Disabled 1 adaptor protein 107:132 Disabled 1 adaptor protein 107:132 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 8 81 theme human 1481:1485 arg1 protein 1492:1498 human Dab1 protein 1481:1498 human Dab1 protein 1481:1498 In addition, we analyzed these conserved sites at our constructed two- and three-dimensional structures of human Dab1 protein. 37067567 12 82 theme signaling 1946:1954 arg1 process 1956:1962 the Dab1 signaling process 1937:1962 the Dab1 signaling process 1937:1962 Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease. 37067567 0 83 link O-linked 53:60 arg1 β-GlcNAcylation 62:76 O-linked β-GlcNAcylation 53:76 O-linked β-GlcNAcylation 53:76 In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates. 37067567 8 84 theme protein 1492:1498 arg1 two- 1440:1443 two- 1440:1443 two- 1440:1443 In addition, we analyzed these conserved sites at our constructed two- and three-dimensional structures of human Dab1 protein. 37067567 8 84 theme protein 1492:1498 arg1 protein 1492:1498 human Dab1 protein 1481:1498 human Dab1 protein 1481:1498 In addition, we analyzed these conserved sites at our constructed two- and three-dimensional structures of human Dab1 protein. 37067567 10 85 theme crosstalk 1623:1631 arg1 sites 1633:1637 these conserved crosstalk sites 1607:1637 these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation 1607:1683 Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. 37067567 10 86 located localized 1690:1698 arg1 region 1712:1717 the coil region 1703:1717 the coil region of the protein model 1703:1738 Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. 37067567 10 86 located localized 1690:1698 arg2 Many 1599:1602 Many 1599:1602 Many 1599:1602 Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. 37067567 10 86 located localized 1690:1698 arg2 sites 1633:1637 these conserved crosstalk sites 1607:1637 these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation 1607:1683 Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. 37067567 1 87 theme reelin 228:233 arg1 signaling 235:243 reelin signaling 228:243 reelin signaling 228:243 Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. 35846740 7 0 theme wild-type 1459:1467 arg1 strain 1469:1474 the wild-type strain 1455:1474 the wild-type strain 1455:1474 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 2 1 theme enzyme 327:332 arg1 β-galactosidase 334:348 the enzyme β-galactosidase 323:348 the enzyme β-galactosidase (BgaA) 323:355 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 2 1 theme enzyme 327:332 arg1 BgaA 351:354 BgaA 351:354 BgaA 351:354 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 4 2 theme precise 849:855 arg1 role 857:860 the precise role 845:860 the precise role of bgaA as a virulence factor in sepsis 845:900 In this study, we performed in vitro and in vivo assays to evaluate the precise role of bgaA as a virulence factor in sepsis. 35846740 6 3 theme neutrophil-mediated 1147:1165 arg1 killing 1167:1173 neutrophil-mediated killing 1147:1173 neutrophil-mediated killing 1147:1173 The deletion of bgaA also reduced pneumococcal survival in human blood by promoting neutrophil-mediated killing, but did not affect pneumococcal survival in mouse blood. 35846740 4 4 theme in 818:819 arg1 assays 826:831 in vitro and in vivo assays 805:831 in vitro and in vivo assays 805:831 In this study, we performed in vitro and in vivo assays to evaluate the precise role of bgaA as a virulence factor in sepsis. 35846740 3 5 theme neutrophil-mediated 680:698 arg1 killing 717:723 human neutrophil-mediated opsonophagocytic killing 674:723 human neutrophil-mediated opsonophagocytic killing 674:723 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 2 6 theme evolutionary 249:260 arg1 analysis 262:269 Our previous molecular evolutionary analysis 226:269 Our previous molecular evolutionary analysis 226:269 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 6 7 theme human 1122:1126 arg1 blood 1128:1132 human blood 1122:1132 human blood 1122:1132 The deletion of bgaA also reduced pneumococcal survival in human blood by promoting neutrophil-mediated killing, but did not affect pneumococcal survival in mouse blood. 35846740 2 8 theme mouse 521:525 arg1 assay 549:553 a mouse intravenous infection assay 519:553 a mouse intravenous infection assay 519:553 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 4 9 dep in 805:806 arg1 vitro 808:812 vitro 808:812 vitro 808:812 In this study, we performed in vitro and in vivo assays to evaluate the precise role of bgaA as a virulence factor in sepsis. 35846740 9 10 theme attractive 1676:1685 arg1 target 1687:1692 an attractive target 1673:1692 an attractive target for drug design and vaccine development to control pneumococcal infection 1673:1766 Taken together, our results suggest that BgaA could be an attractive target for drug design and vaccine development to control pneumococcal infection. 35846740 9 10 theme attractive 1676:1685 arg1 BgaA 1659:1662 BgaA 1659:1662 BgaA 1659:1662 Taken together, our results suggest that BgaA could be an attractive target for drug design and vaccine development to control pneumococcal infection. 35846740 7 11 theme innate 1348:1353 arg1 pathways 1364:1371 upregulated host innate immunity pathways 1331:1371 upregulated host innate immunity pathways 1331:1371 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 3 12 from resistance 660:669 arg1 glycans 651:657 N-linked glycans 642:657 N-linked glycans 642:657 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 2 13 contain had 358:360 arg1 bgaA 308:311 the S. pneumoniae gene bgaA 285:311 the S. pneumoniae gene bgaA 285:311 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 2 13 contain had 358:360 arg2 proportion 369:378 a high proportion 362:378 a high proportion of codons 362:388 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 3 14 theme multifunctional 566:580 arg1 BgaA 556:559 BgaA 556:559 BgaA 556:559 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 3 14 theme multifunctional 566:580 arg1 protein 582:588 a multifunctional protein 564:588 a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells 564:774 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 7 15 theme upregulated 1331:1341 arg1 pathways 1364:1371 upregulated host innate immunity pathways 1331:1371 upregulated host innate immunity pathways 1331:1371 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 2 16 dep S. 289:290 arg1 pneumoniae 292:301 pneumoniae 292:301 pneumoniae 292:301 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 3 17 theme human 753:757 arg1 cells 770:774 human epithelial cells 753:774 human epithelial cells 753:774 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 2 18 theme infection 539:547 arg1 assay 549:553 a mouse intravenous infection assay 519:553 a mouse intravenous infection assay 519:553 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 5 19 theme human 1009:1013 arg1 epithelial 1020:1029 human lung epithelial 1009:1029 human lung epithelial 1009:1029 Our in vitro assays showed that the deletion of bgaA significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. 35846740 2 20 theme previous 230:237 arg1 analysis 262:269 Our previous molecular evolutionary analysis 226:269 Our previous molecular evolutionary analysis 226:269 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 9 21 theme vaccine 1714:1720 arg1 development 1722:1732 vaccine development 1714:1732 vaccine development 1714:1732 Taken together, our results suggest that BgaA could be an attractive target for drug design and vaccine development to control pneumococcal infection. 35846740 4 22 theme virulence 875:883 arg1 factor 885:890 a virulence factor 873:890 a virulence factor in sepsis 873:900 In this study, we performed in vitro and in vivo assays to evaluate the precise role of bgaA as a virulence factor in sepsis. 35846740 7 23 theme bgaA-deleted 1294:1305 arg1 strain 1314:1319 an S. pneumoniae bgaA-deleted mutant strain 1277:1319 an S. pneumoniae bgaA-deleted mutant strain 1277:1319 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 1 24 theme invasive 133:140 arg1 sepsis 186:191 sepsis 186:191 sepsis 186:191 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 1 24 theme invasive 133:140 arg1 meningitis 170:179 meningitis 170:179 meningitis 170:179 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 1 24 theme invasive 133:140 arg1 diseases 142:149 invasive diseases 133:149 invasive diseases such as pneumonia, meningitis, and sepsis 133:191 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 1 24 theme invasive 133:140 arg1 pneumonia 159:167 pneumonia 159:167 pneumonia 159:167 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 2 25 theme intravenous 527:537 arg1 assay 549:553 a mouse intravenous infection assay 519:553 a mouse intravenous infection assay 519:553 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 0 26 theme Mouse 68:72 arg1 Model 81:85 a Mouse Sepsis Model 66:85 a Mouse Sepsis Model 66:85 Pneumococcal BgaA Promotes Host Organ Bleeding and Coagulation in a Mouse Sepsis Model. 35846740 2 27 theme host 501:504 arg1 mortality 506:514 host mortality 501:514 host mortality 501:514 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 1 28 with cause 124:128 arg1 mortality 215:223 high associated mortality 199:223 high associated mortality 199:223 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 7 29 theme pneumoniae 1283:1292 arg1 strain 1314:1319 an S. pneumoniae bgaA-deleted mutant strain 1277:1319 an S. pneumoniae bgaA-deleted mutant strain 1277:1319 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 3 30 from adherence 740:748 arg1 glycans 651:657 N-linked glycans 642:657 N-linked glycans 642:657 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 0 31 theme Pneumococcal 0:11 arg1 BgaA 13:16 Pneumococcal BgaA 0:16 Pneumococcal BgaA 0:16 Pneumococcal BgaA Promotes Host Organ Bleeding and Coagulation in a Mouse Sepsis Model. 35846740 2 32 theme negative 396:403 arg1 selection 405:413 negative selection 396:413 negative selection among the examined pneumococcal genes 396:451 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 2 33 theme codons 383:388 arg1 proportion 369:378 a high proportion 362:378 a high proportion of codons 362:388 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 5 34 theme in 907:908 arg1 assays 916:921 Our in vitro assays 903:921 Our in vitro assays 903:921 Our in vitro assays showed that the deletion of bgaA significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. 35846740 8 35 theme multifunctional 1524:1538 arg1 BgaA 1504:1507 BgaA 1504:1507 BgaA 1504:1507 These results suggest that BgaA functions as a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation. 35846740 8 35 theme multifunctional 1524:1538 arg1 factor 1550:1555 a multifunctional virulence factor 1522:1555 a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation 1522:1615 These results suggest that BgaA functions as a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation. 35846740 3 36 theme terminal 620:627 arg1 galactose 629:637 terminal galactose 620:637 terminal galactose in N-linked glycans 620:657 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 2 37 theme examined 425:432 arg1 genes 447:451 the examined pneumococcal genes 421:451 the examined pneumococcal genes 421:451 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 5 38 theme bacterial 982:990 arg1 association 992:1002 the bacterial association 978:1002 the bacterial association with human lung epithelial and vascular endothelial cells 978:1060 Our in vitro assays showed that the deletion of bgaA significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. 35846740 7 39 theme sepsis 1244:1249 arg1 model 1251:1255 a mouse sepsis model 1236:1255 a mouse sepsis model 1236:1255 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 3 40 link N-linked 642:649 arg1 glycans 651:657 N-linked glycans 642:657 N-linked glycans 642:657 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 8 41 theme host 1576:1579 arg1 damage 1588:1593 host tissue damage 1576:1593 host tissue damage 1576:1593 These results suggest that BgaA functions as a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation. 35846740 3 42 from galactose 629:637 arg1 glycans 651:657 N-linked glycans 642:657 N-linked glycans 642:657 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 1 43 theme associated 204:213 arg1 mortality 215:223 high associated mortality 199:223 high associated mortality 199:223 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 5 44 theme bgaA 951:954 arg1 deletion 939:946 the deletion 935:946 the deletion of bgaA 935:954 Our in vitro assays showed that the deletion of bgaA significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. 35846740 3 45 theme human 674:678 arg1 killing 717:723 human neutrophil-mediated opsonophagocytic killing 674:723 human neutrophil-mediated opsonophagocytic killing 674:723 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 8 46 theme blood 1599:1603 arg1 coagulation 1605:1615 blood coagulation 1599:1615 blood coagulation 1599:1615 These results suggest that BgaA functions as a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation. 35846740 7 47 theme suppressed 1374:1383 arg1 damage 1392:1397 suppressed tissue damage 1374:1397 suppressed tissue damage 1374:1397 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 7 48 theme blood 1404:1408 arg1 coagulation 1410:1420 blood coagulation 1404:1420 blood coagulation 1404:1420 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 3 49 theme opsonophagocytic 700:715 arg1 killing 717:723 human neutrophil-mediated opsonophagocytic killing 674:723 human neutrophil-mediated opsonophagocytic killing 674:723 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 6 50 theme mouse 1220:1224 arg1 blood 1226:1230 mouse blood 1220:1230 mouse blood 1220:1230 The deletion of bgaA also reduced pneumococcal survival in human blood by promoting neutrophil-mediated killing, but did not affect pneumococcal survival in mouse blood. 35846740 2 51 theme gene 303:306 arg1 bgaA 308:311 the S. pneumoniae gene bgaA 285:311 the S. pneumoniae gene bgaA 285:311 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 7 52 theme tissue 1385:1390 arg1 damage 1392:1397 suppressed tissue damage 1374:1397 suppressed tissue damage 1374:1397 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 2 53 theme S. 289:290 arg1 bgaA 308:311 the S. pneumoniae gene bgaA 285:311 the S. pneumoniae gene bgaA 285:311 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 6 54 theme pneumococcal 1097:1108 arg1 survival 1110:1117 pneumococcal survival 1097:1117 pneumococcal survival 1097:1117 The deletion of bgaA also reduced pneumococcal survival in human blood by promoting neutrophil-mediated killing, but did not affect pneumococcal survival in mouse blood. 35846740 3 55 theme bacterial 730:738 arg1 adherence 740:748 bacterial adherence 730:748 bacterial adherence to human epithelial cells 730:774 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 4 56 from factor 885:890 arg1 sepsis 895:900 sepsis 895:900 sepsis 895:900 In this study, we performed in vitro and in vivo assays to evaluate the precise role of bgaA as a virulence factor in sepsis. 35846740 6 57 theme pneumococcal 1195:1206 arg1 survival 1208:1215 pneumococcal survival 1195:1215 pneumococcal survival in mouse blood 1195:1230 The deletion of bgaA also reduced pneumococcal survival in human blood by promoting neutrophil-mediated killing, but did not affect pneumococcal survival in mouse blood. 35846740 9 58 theme pneumococcal 1745:1756 arg1 infection 1758:1766 pneumococcal infection 1745:1766 pneumococcal infection 1745:1766 Taken together, our results suggest that BgaA could be an attractive target for drug design and vaccine development to control pneumococcal infection. 35846740 5 59 theme endothelial 1044:1054 arg1 cells 1056:1060 vascular endothelial cells 1035:1060 vascular endothelial cells 1035:1060 Our in vitro assays showed that the deletion of bgaA significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. 35846740 9 60 theme drug 1698:1701 arg1 design 1703:1708 drug design 1698:1708 drug design 1698:1708 Taken together, our results suggest that BgaA could be an attractive target for drug design and vaccine development to control pneumococcal infection. 35846740 7 61 theme host 1343:1346 arg1 pathways 1364:1371 upregulated host innate immunity pathways 1331:1371 upregulated host innate immunity pathways 1331:1371 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 3 62 theme epithelial 759:768 arg1 cells 770:774 human epithelial cells 753:774 human epithelial cells 753:774 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 2 63 theme molecular 239:247 arg1 analysis 262:269 Our previous molecular evolutionary analysis 226:269 Our previous molecular evolutionary analysis 226:269 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 1 64 theme major 118:122 arg1 cause 124:128 a major cause 116:128 a major cause of invasive diseases such as pneumonia, meningitis, and sepsis 116:191 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 1 64 theme major 118:122 arg1 pneumoniae 102:111 Streptococcus pneumoniae 88:111 Streptococcus pneumoniae 88:111 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 4 65 theme bgaA 865:868 arg1 role 857:860 the precise role 845:860 the precise role of bgaA as a virulence factor in sepsis 845:900 In this study, we performed in vitro and in vivo assays to evaluate the precise role of bgaA as a virulence factor in sepsis. 35846740 6 66 from survival 1208:1215 arg1 blood 1226:1230 mouse blood 1220:1230 mouse blood 1220:1230 The deletion of bgaA also reduced pneumococcal survival in human blood by promoting neutrophil-mediated killing, but did not affect pneumococcal survival in mouse blood. 35846740 5 67 theme lung 1015:1018 arg1 epithelial 1020:1029 human lung epithelial 1009:1029 human lung epithelial 1009:1029 Our in vitro assays showed that the deletion of bgaA significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. 35846740 7 68 theme mutant 1307:1312 arg1 strain 1314:1319 an S. pneumoniae bgaA-deleted mutant strain 1277:1319 an S. pneumoniae bgaA-deleted mutant strain 1277:1319 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 5 69 dep in 907:908 arg1 vitro 910:914 vitro 910:914 vitro 910:914 Our in vitro assays showed that the deletion of bgaA significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. 35846740 0 70 theme Sepsis 74:79 arg1 Model 81:85 a Mouse Sepsis Model 66:85 a Mouse Sepsis Model 66:85 Pneumococcal BgaA Promotes Host Organ Bleeding and Coagulation in a Mouse Sepsis Model. 35846740 1 71 theme diseases 142:149 arg1 cause 124:128 a major cause 116:128 a major cause of invasive diseases such as pneumonia, meningitis, and sepsis 116:191 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 1 71 theme diseases 142:149 arg1 pneumoniae 102:111 Streptococcus pneumoniae 88:111 Streptococcus pneumoniae 88:111 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 7 72 theme S. 1280:1281 arg1 strain 1314:1319 an S. pneumoniae bgaA-deleted mutant strain 1277:1319 an S. pneumoniae bgaA-deleted mutant strain 1277:1319 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 2 73 theme bgaA 474:477 arg1 deletion 462:469 deletion 462:469 deletion of bgaA 462:477 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 5 74 with association 992:1002 arg1 cells 1056:1060 vascular endothelial cells 1035:1060 vascular endothelial cells 1035:1060 Our in vitro assays showed that the deletion of bgaA significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. 35846740 5 74 with association 992:1002 arg1 epithelial 1020:1029 human lung epithelial 1009:1029 human lung epithelial 1009:1029 Our in vitro assays showed that the deletion of bgaA significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. 35846740 4 75 dep in 818:819 arg1 vivo 821:824 vivo 821:824 vivo 821:824 In this study, we performed in vitro and in vivo assays to evaluate the precise role of bgaA as a virulence factor in sepsis. 35846740 1 76 theme Streptococcus 88:100 arg1 cause 124:128 a major cause 116:128 a major cause of invasive diseases such as pneumonia, meningitis, and sepsis 116:191 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 1 76 theme Streptococcus 88:100 arg1 pneumoniae 102:111 Streptococcus pneumoniae 88:111 Streptococcus pneumoniae 88:111 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35846740 8 77 theme virulence 1540:1548 arg1 BgaA 1504:1507 BgaA 1504:1507 BgaA 1504:1507 These results suggest that BgaA functions as a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation. 35846740 8 77 theme virulence 1540:1548 arg1 factor 1550:1555 a multifunctional virulence factor 1522:1555 a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation 1522:1615 These results suggest that BgaA functions as a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation. 35846740 2 78 theme pneumococcal 434:445 arg1 genes 447:451 the examined pneumococcal genes 421:451 the examined pneumococcal genes 421:451 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 2 79 theme high 364:367 arg1 proportion 369:378 a high proportion 362:378 a high proportion of codons 362:388 Our previous molecular evolutionary analysis revealed that the S. pneumoniae gene bgaA, encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of bgaA significantly reduced host mortality in a mouse intravenous infection assay. 35846740 7 80 theme mouse 1238:1242 arg1 model 1251:1255 a mouse sepsis model 1236:1255 a mouse sepsis model 1236:1255 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 3 81 theme N-linked 642:649 arg1 glycans 651:657 N-linked glycans 642:657 N-linked glycans 642:657 BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in N-linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. 35846740 4 82 theme in 805:806 arg1 assays 826:831 in vitro and in vivo assays 805:831 in vitro and in vivo assays 805:831 In this study, we performed in vitro and in vivo assays to evaluate the precise role of bgaA as a virulence factor in sepsis. 35846740 5 83 theme vascular 1035:1042 arg1 cells 1056:1060 vascular endothelial cells 1035:1060 vascular endothelial cells 1035:1060 Our in vitro assays showed that the deletion of bgaA significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. 35846740 7 84 theme immunity 1355:1362 arg1 pathways 1364:1371 upregulated host innate immunity pathways 1331:1371 upregulated host innate immunity pathways 1331:1371 In a mouse sepsis model, mice infected with an S. pneumoniae bgaA-deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. 35846740 6 85 theme bgaA 1079:1082 arg1 deletion 1067:1074 The deletion 1063:1074 The deletion of bgaA 1063:1082 The deletion of bgaA also reduced pneumococcal survival in human blood by promoting neutrophil-mediated killing, but did not affect pneumococcal survival in mouse blood. 35846740 8 86 theme tissue 1581:1586 arg1 damage 1588:1593 host tissue damage 1576:1593 host tissue damage 1576:1593 These results suggest that BgaA functions as a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation. 35846740 1 87 theme high 199:202 arg1 mortality 215:223 high associated mortality 199:223 high associated mortality 199:223 Streptococcus pneumoniae is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. 35831291 6 0 theme prion 916:920 arg1 fibrils 922:928 wildtype RML prion fibrils 903:928 wildtype RML prion fibrils 903:928 Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. 35831291 4 1 theme detailed 576:583 arg1 comparisons 585:595 detailed comparisons 576:595 detailed comparisons 576:595 However, detailed comparisons reveal variations in these shared structural topologies and other features. 35831291 4 2 from variations 604:613 arg1 topologies 642:651 these shared structural topologies 618:651 these shared structural topologies 618:651 However, detailed comparisons reveal variations in these shared structural topologies and other features. 35831291 4 2 from variations 604:613 arg1 features 663:670 other features 657:670 other features 657:670 However, detailed comparisons reveal variations in these shared structural topologies and other features. 35831291 6 3 theme accompanying 936:947 arg1 paper 949:953 an accompanying paper 933:953 an accompanying paper 933:953 Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. 35831291 4 4 theme structural 631:640 arg1 topologies 642:651 these shared structural topologies 618:651 these shared structural topologies 618:651 However, detailed comparisons reveal variations in these shared structural topologies and other features. 35831291 1 5 theme prion 150:154 arg1 strains 156:162 prion strains 150:162 prion strains 150:162 Little is known about the structural basis of prion strains. 35831291 7 6 theme common 1095:1100 arg1 features 1127:1134 both common and divergent structural features 1090:1134 both common and divergent structural features of prion strains 1090:1151 This work demonstrates both common and divergent structural features of prion strains at the near-atomic level. 35831291 0 7 theme distinct 86:93 arg1 strains 95:101 distinct strains 86:101 distinct strains 86:101 Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains. 35831291 0 8 from variations 50:59 arg1 motifs 71:76 shared motifs 64:76 shared motifs between distinct strains 64:101 Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains. 35831291 7 9 theme near-atomic 1160:1170 arg1 level 1172:1176 the near-atomic level 1156:1176 the near-atomic level 1156:1176 This work demonstrates both common and divergent structural features of prion strains at the near-atomic level. 35831291 3 10 dep ex 482:483 arg1 vivo 485:488 vivo 485:488 vivo 485:488 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 3 11 theme ex 482:483 arg1 zipper 540:545 an amino-proximal steric zipper 515:545 an amino-proximal steric zipper 515:545 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 3 11 theme ex 482:483 arg1 β-arches 557:564 three β-arches 551:564 three β-arches 551:564 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 3 11 theme ex 482:483 arg1 strains 496:502 these ex vivo prion strains 476:502 these ex vivo prion strains 476:502 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 5 12 theme glycophosphatidylinositol 741:765 arg1 anchors 767:773 glycophosphatidylinositol anchors 741:773 glycophosphatidylinositol anchors 741:773 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 6 13 theme RML 912:914 arg1 fibrils 922:928 wildtype RML prion fibrils 903:928 wildtype RML prion fibrils 903:928 Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. 35831291 7 14 theme strains 1145:1151 arg1 features 1127:1134 both common and divergent structural features 1090:1134 both common and divergent structural features of prion strains 1090:1151 This work demonstrates both common and divergent structural features of prion strains at the near-atomic level. 35831291 2 15 theme in-register 399:409 arg1 core 425:428 a parallel in-register β-sheet-based core 388:428 a parallel in-register β-sheet-based core 388:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 2 16 theme fibrils 276:282 arg1 structure 238:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure 181:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 181:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 1 17 theme strains 156:162 arg1 basis 141:145 the structural basis 126:145 the structural basis of prion strains 126:162 Little is known about the structural basis of prion strains. 35831291 6 18 theme wildtype 903:910 arg1 fibrils 922:928 wildtype RML prion fibrils 903:928 wildtype RML prion fibrils 903:928 Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. 35831291 6 19 theme amyloid 1040:1046 arg1 conformation 1053:1064 the amyloid core conformation 1036:1064 the amyloid core conformation 1036:1064 Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. 35831291 6 20 theme structure 873:881 arg1 similarity 840:849 the similarity 836:849 the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper 836:953 Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. 35831291 2 21 theme brain-derived 262:274 arg1 fibrils 276:282 infectious brain-derived fibrils 251:282 infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 251:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 3 22 theme structural 439:448 arg1 motifs 450:455 Several structural motifs 431:455 Several structural motifs 431:455 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 2 23 theme scrapie 312:318 arg1 strain 320:325 the mouse anchorless RML scrapie strain 287:325 the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 287:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 5 24 theme N-linked 805:812 arg1 glycans 814:820 N-linked glycans 805:820 N-linked glycans 805:820 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 0 25 theme Cryo-EM 0:6 arg1 structure 8:16 Cryo-EM structure 0:16 Cryo-EM structure of anchorless RML prion 0:40 Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains. 35831291 7 26 theme prion 1139:1143 arg1 strains 1145:1151 prion strains 1139:1151 prion strains 1139:1151 This work demonstrates both common and divergent structural features of prion strains at the near-atomic level. 35831291 2 27 theme RML 308:310 arg1 strain 320:325 the mouse anchorless RML scrapie strain 287:325 the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 287:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 2 28 theme 263K 371:374 arg1 strain 376:381 the recently determined hamster 263K strain 339:381 the recently determined hamster 263K strain 339:381 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 0 29 theme anchorless 21:30 arg1 prion 36:40 anchorless RML prion 21:40 anchorless RML prion 21:40 Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains. 35831291 2 30 link brain-derived 262:274 arg1 fibrils 276:282 infectious brain-derived fibrils 251:282 infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 251:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 7 31 theme structural 1116:1125 arg1 features 1127:1134 both common and divergent structural features 1090:1134 both common and divergent structural features of prion strains 1090:1151 This work demonstrates both common and divergent structural features of prion strains at the near-atomic level. 35831291 5 32 link N-linked 805:812 arg1 glycans 814:820 N-linked glycans 805:820 N-linked glycans 805:820 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 2 33 theme anchorless 297:306 arg1 strain 320:325 the mouse anchorless RML scrapie strain 287:325 the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 287:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 2 34 theme β-sheet-based 411:423 arg1 core 425:428 a parallel in-register β-sheet-based core 388:428 a parallel in-register β-sheet-based core 388:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 3 35 theme amino-proximal 518:531 arg1 zipper 540:545 an amino-proximal steric zipper 515:545 an amino-proximal steric zipper 515:545 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 2 36 theme mouse 291:295 arg1 strain 320:325 the mouse anchorless RML scrapie strain 287:325 the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 287:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 1 37 theme structural 130:139 arg1 basis 141:145 the structural basis 126:145 the structural basis of prion strains 126:162 Little is known about the structural basis of prion strains. 35831291 0 38 theme prion 36:40 arg1 structure 8:16 Cryo-EM structure 0:16 Cryo-EM structure of anchorless RML prion 0:40 Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains. 35831291 6 39 theme post-translational 976:993 arg1 modifications 995:1007 these post-translational modifications 970:1007 these post-translational modifications 970:1007 Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. 35831291 5 40 theme anchorless 714:723 arg1 prions 729:734 the anchorless RML prions 710:734 the anchorless RML prions 710:734 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 5 40 theme anchorless 714:723 arg1 deficient 792:800 deficient 792:800 deficient 792:800 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 4 41 theme other 657:661 arg1 features 663:670 other features 657:670 other features 657:670 However, detailed comparisons reveal variations in these shared structural topologies and other features. 35831291 2 42 theme cryo-electron 207:219 arg1 structure 238:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure 181:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 181:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 2 43 theme parallel 390:397 arg1 core 425:428 a parallel in-register β-sheet-based core 388:428 a parallel in-register β-sheet-based core 388:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 0 44 theme RML 32:34 arg1 prion 36:40 anchorless RML prion 21:40 anchorless RML prion 21:40 Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains. 35831291 5 45 theme RML 725:727 arg1 prions 729:734 the anchorless RML prions 710:734 the anchorless RML prions 710:734 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 5 45 theme RML 725:727 arg1 deficient 792:800 deficient 792:800 deficient 792:800 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 2 46 theme resolution 196:205 arg1 structure 238:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure 181:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 181:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 2 47 contain has 384:386 arg2 core 425:428 a parallel in-register β-sheet-based core 388:428 a parallel in-register β-sheet-based core 388:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 2 47 contain has 384:386 arg1 strain 320:325 the mouse anchorless RML scrapie strain 287:325 the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 287:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 7 48 theme divergent 1106:1114 arg1 features 1127:1134 both common and divergent structural features 1090:1134 both common and divergent structural features of prion strains 1090:1151 This work demonstrates both common and divergent structural features of prion strains at the near-atomic level. 35831291 6 49 theme anchorless 858:867 arg1 structure 873:881 our anchorless RML structure 854:881 our anchorless RML structure 854:881 Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. 35831291 5 50 theme wildtype 689:696 arg1 prions 702:707 wildtype RML prions 689:707 wildtype RML prions 689:707 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 6 51 theme RML 869:871 arg1 structure 873:881 our anchorless RML structure 854:881 our anchorless RML structure 854:881 Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. 35831291 2 52 theme 3.0 Å 189:193 arg1 structure 238:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure 181:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 181:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 3 53 theme prion 490:494 arg1 zipper 540:545 an amino-proximal steric zipper 515:545 an amino-proximal steric zipper 515:545 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 3 53 theme prion 490:494 arg1 β-arches 557:564 three β-arches 551:564 three β-arches 551:564 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 3 53 theme prion 490:494 arg1 strains 496:502 these ex vivo prion strains 476:502 these ex vivo prion strains 476:502 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 3 54 theme Several 431:437 arg1 motifs 450:455 Several structural motifs 431:455 Several structural motifs 431:455 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 5 55 theme RML 698:700 arg1 prions 702:707 wildtype RML prions 689:707 wildtype RML prions 689:707 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 2 56 theme high 183:186 arg1 structure 238:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure 181:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 181:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 2 57 theme infectious 251:260 arg1 fibrils 276:282 infectious brain-derived fibrils 251:282 infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 251:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 3 58 theme steric 533:538 arg1 zipper 540:545 an amino-proximal steric zipper 515:545 an amino-proximal steric zipper 515:545 Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. 35831291 2 59 theme strain 320:325 arg1 fibrils 276:282 infectious brain-derived fibrils 251:282 infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 251:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 0 60 theme shared 64:69 arg1 motifs 71:76 shared motifs 64:76 shared motifs between distinct strains 64:101 Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains. 35831291 2 61 theme hamster 363:369 arg1 strain 376:381 the recently determined hamster 263K strain 339:381 the recently determined hamster 263K strain 339:381 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 5 62 from deficient 792:800 arg1 glycans 814:820 N-linked glycans 805:820 N-linked glycans 805:820 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 4 63 theme shared 624:629 arg1 topologies 642:651 these shared structural topologies 618:651 these shared structural topologies 618:651 However, detailed comparisons reveal variations in these shared structural topologies and other features. 35831291 5 64 from glycans 814:820 arg1 prions 729:734 the anchorless RML prions 710:734 the anchorless RML prions 710:734 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 5 64 from glycans 814:820 arg1 deficient 792:800 deficient 792:800 deficient 792:800 Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. 35831291 2 65 theme microscopy-based 221:236 arg1 structure 238:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure 181:246 a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core 181:428 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 2 66 theme determined 352:361 arg1 strain 376:381 the recently determined hamster 263K strain 339:381 the recently determined hamster 263K strain 339:381 Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. 35831291 6 67 theme core 1048:1051 arg1 conformation 1053:1064 the amyloid core conformation 1036:1064 the amyloid core conformation 1036:1064 Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. 35896117 6 0 theme families 886:893 arg1 cohort 870:875 a cohort 868:875 a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), 868:1034 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 10 1 theme heterozygous 1645:1656 arg1 loss 1658:1661 heterozygous loss 1645:1661 heterozygous loss of ALG5 1645:1669 We also show that ALG5 is required for PC1 maturation and membrane and ciliary localization and that heterozygous loss of ALG5 affects PC1 maturation. 35896117 1 2 theme decline 269:275 arg1 development 209:219 the development 205:219 the development of kidney cysts and progressive kidney function decline 205:275 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 4 3 theme multiplex 535:543 arg1 family 574:579 a large multiplex genetically unresolved (GUR) family 527:579 a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms 527:611 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 8 4 with consistent 1243:1252 arg1 kidneys 1307:1313 non-enlarged cystic kidneys 1287:1313 non-enlarged cystic kidneys 1287:1313 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 8 4 with consistent 1243:1252 arg1 cysts 1335:1339 few or no liver cysts 1319:1339 few or no liver cysts 1319:1339 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 6 5 theme Genomes 1120:1126 arg1 data 1136:1139 Genomics England 100,000 Genomes Project data 1095:1139 Genomics England 100,000 Genomes Project data 1095:1139 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 6 theme England 1104:1110 arg1 data 1136:1139 Genomics England 100,000 Genomes Project data 1095:1139 Genomics England 100,000 Genomes Project data 1095:1139 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 11 7 theme monoallelic 1730:1740 arg1 variants 1742:1749 monoallelic variants 1730:1749 monoallelic variants of ALG5 1730:1757 Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline. 35896117 6 8 theme kidney 956:961 arg1 GUR 981:983 GUR 981:983 GUR 981:983 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 8 theme kidney 956:961 arg1 diseases 963:970 ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases 900:970 ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD) 900:978 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 8 theme kidney 956:961 arg1 naive 998:1002 naive 998:1002 naive 998:1002 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 8 theme kidney 956:961 arg1 ADTKD 973:977 ADTKD 973:977 ADTKD 973:977 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 11 9 theme multiple 1817:1824 arg1 cysts 1839:1843 multiple small kidney cysts 1817:1843 multiple small kidney cysts 1817:1843 Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline. 35896117 1 10 theme kidney 224:229 arg1 cysts 231:235 kidney cysts 224:235 kidney cysts 224:235 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 6 11 theme autosomal-dominant 918:935 arg1 GUR 981:983 GUR 981:983 GUR 981:983 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 11 theme autosomal-dominant 918:935 arg1 diseases 963:970 ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases 900:970 ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD) 900:978 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 11 theme autosomal-dominant 918:935 arg1 naive 998:1002 naive 998:1002 naive 998:1002 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 11 theme autosomal-dominant 918:935 arg1 ADTKD 973:977 ADTKD 973:977 ADTKD 973:977 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 11 12 theme kidney 1885:1890 arg1 decline 1901:1907 kidney function decline 1885:1907 kidney function decline 1885:1907 Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline. 35896117 1 13 theme dominant 132:139 arg1 ADPKD 168:172 ADPKD 168:172 ADPKD 168:172 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 1 13 theme dominant 132:139 arg1 disease 159:165 autosomal dominant polycystic kidney disease 122:165 the autosomal dominant polycystic kidney disease (ADPKD) spectrum 118:182 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 6 14 theme ADPKD-like 900:909 arg1 GUR 981:983 GUR 981:983 GUR 981:983 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 14 theme ADPKD-like 900:909 arg1 diseases 963:970 ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases 900:970 ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD) 900:978 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 14 theme ADPKD-like 900:909 arg1 naive 998:1002 naive 998:1002 naive 998:1002 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 14 theme ADPKD-like 900:909 arg1 ADTKD 973:977 ADTKD 973:977 ADTKD 973:977 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 8 15 theme affected 1264:1271 arg1 members 1273:1279 the 23 affected members 1257:1279 the 23 affected members 1257:1279 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 4 16 dep unresolved 557:566 arg1 GUR 569:571 GUR 569:571 GUR 569:571 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 8 17 from consistent 1243:1252 arg1 members 1273:1279 the 23 affected members 1257:1279 the 23 affected members 1257:1279 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 1 18 theme kidney 152:157 arg1 ADPKD 168:172 ADPKD 168:172 ADPKD 168:172 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 1 18 theme kidney 152:157 arg1 disease 159:165 autosomal dominant polycystic kidney disease 122:165 the autosomal dominant polycystic kidney disease (ADPKD) spectrum 118:182 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 1 19 theme polycystic 141:150 arg1 ADPKD 168:172 ADPKD 168:172 ADPKD 168:172 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 1 19 theme polycystic 141:150 arg1 disease 159:165 autosomal dominant polycystic kidney disease 122:165 the autosomal dominant polycystic kidney disease (ADPKD) spectrum 118:182 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 4 20 theme monoallelic 630:640 arg1 c.703_704delCA 662:675 c.703_704delCA 662:675 c.703_704delCA 662:675 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 4 20 theme monoallelic 630:640 arg1 variant 653:659 a monoallelic frameshift variant 628:659 a monoallelic frameshift variant (c.703_704delCA) 628:676 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 5 21 theme endoplasmic-reticulum-resident 703:732 arg1 ALG5 687:690 ALG5 687:690 ALG5 687:690 ALG5 encodes an endoplasmic-reticulum-resident enzyme required for addition of glucose molecules to the assembling N-glycan precursors. 35896117 5 21 theme endoplasmic-reticulum-resident 703:732 arg1 enzyme 734:739 an endoplasmic-reticulum-resident enzyme 700:739 an endoplasmic-reticulum-resident enzyme required for addition of glucose molecules to the assembling N-glycan precursors 700:820 ALG5 encodes an endoplasmic-reticulum-resident enzyme required for addition of glucose molecules to the assembling N-glycan precursors. 35896117 5 22 theme assembling 791:800 arg1 precursors 811:820 the assembling N-glycan precursors 787:820 the assembling N-glycan precursors 787:820 ALG5 encodes an endoplasmic-reticulum-resident enzyme required for addition of glucose molecules to the assembling N-glycan precursors. 35896117 8 23 theme non-enlarged 1287:1298 arg1 kidneys 1307:1313 non-enlarged cystic kidneys 1287:1313 non-enlarged cystic kidneys 1287:1313 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 0 24 theme interstitial 82:93 arg1 fibrosis 95:102 interstitial fibrosis 82:102 interstitial fibrosis 82:102 Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis. 35896117 10 25 theme PC1 1583:1585 arg1 maturation 1587:1596 PC1 maturation 1583:1596 PC1 maturation 1583:1596 We also show that ALG5 is required for PC1 maturation and membrane and ciliary localization and that heterozygous loss of ALG5 affects PC1 maturation. 35896117 11 26 theme small 1826:1830 arg1 cysts 1839:1843 multiple small kidney cysts 1817:1843 multiple small kidney cysts 1817:1843 Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline. 35896117 0 27 theme Monoallelic 0:10 arg1 variants 28:35 Monoallelic pathogenic ALG5 variants 0:35 Monoallelic pathogenic ALG5 variants 0:35 Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis. 35896117 9 28 theme chain 1511:1515 arg1 synthesis 1485:1493 the synthesis 1481:1493 the synthesis of the N-glycan chain in renal epithelial cells 1481:1541 We demonstrate that ALG5 haploinsufficiency is sufficient to alter the synthesis of the N-glycan chain in renal epithelial cells. 35896117 0 29 theme ALG5 23:26 arg1 variants 28:35 Monoallelic pathogenic ALG5 variants 0:35 Monoallelic pathogenic ALG5 variants 0:35 Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis. 35896117 9 30 theme renal 1520:1524 arg1 cells 1537:1541 renal epithelial cells 1520:1541 renal epithelial cells 1520:1541 We demonstrate that ALG5 haploinsufficiency is sufficient to alter the synthesis of the N-glycan chain in renal epithelial cells. 35896117 6 31 theme genetic 1007:1013 arg1 testing 1015:1021 genetic testing 1007:1021 genetic testing (n = 1,076) 1007:1033 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 31 theme genetic 1007:1013 arg1 1,076 1028:1032 n = 1,076 1024:1032 n = 1,076 1024:1032 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 4 32 theme whole-exome 501:511 arg1 sequencing 513:522 whole-exome sequencing 501:522 whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms 501:611 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 11 33 theme progressive 1846:1856 arg1 fibrosis 1871:1878 progressive interstitial fibrosis 1846:1878 progressive interstitial fibrosis 1846:1878 Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline. 35896117 2 34 theme other 373:377 arg1 genes 379:383 other genes 373:383 other genes 373:383 PKD1 and PKD2, encoding polycystin (PC)1 and 2, are the two major genes associated with ADPKD; other genes include IFT140, GANAB, DNAJB11, and ALG9. 35896117 6 35 theme additional 835:844 arg1 families 846:853 additional families 835:853 additional families 835:853 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 5 36 theme glucose 766:772 arg1 molecules 774:782 glucose molecules 766:782 glucose molecules 766:782 ALG5 encodes an endoplasmic-reticulum-resident enzyme required for addition of glucose molecules to the assembling N-glycan precursors. 35896117 8 37 theme kidney 1371:1376 arg1 disease 1378:1384 end-stage kidney disease 1361:1384 end-stage kidney disease 1361:1384 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 1 38 theme cysts 231:235 arg1 development 209:219 the development 205:219 the development of kidney cysts and progressive kidney function decline 205:275 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 6 39 with families 886:893 arg1 GUR 981:983 GUR 981:983 GUR 981:983 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 39 with families 886:893 arg1 diseases 963:970 ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases 900:970 ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD) 900:978 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 39 with families 886:893 arg1 naive 998:1002 naive 998:1002 naive 998:1002 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 39 with families 886:893 arg1 ADTKD 973:977 ADTKD 973:977 ADTKD 973:977 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 10 40 theme ALG5 1666:1669 arg1 loss 1658:1661 heterozygous loss 1645:1661 heterozygous loss of ALG5 1645:1669 We also show that ALG5 is required for PC1 maturation and membrane and ciliary localization and that heterozygous loss of ALG5 affects PC1 maturation. 35896117 1 41 theme progressive 241:251 arg1 decline 269:275 progressive kidney function decline 241:275 progressive kidney function decline 241:275 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 6 42 theme targeted 1039:1046 arg1 sequencing 1067:1076 targeted massively parallel sequencing 1039:1076 targeted massively parallel sequencing 1039:1076 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 0 43 theme pathogenic 12:21 arg1 variants 28:35 Monoallelic pathogenic ALG5 variants 0:35 Monoallelic pathogenic ALG5 variants 0:35 Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis. 35896117 11 44 theme ADPKD-spectrum 1785:1798 arg1 disorder 1769:1776 a disorder 1767:1776 a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline 1767:1907 Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline. 35896117 1 45 theme function 260:267 arg1 decline 269:275 progressive kidney function decline 241:275 progressive kidney function decline 241:275 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 3 46 theme families 478:485 arg1 families 478:485 the families 474:485 the families 474:485 Genetic testing remains inconclusive in ∼7% of the families. 35896117 3 46 theme families 478:485 arg1 % 469:469 ∼7% 467:469 ∼7% of the families 467:485 Genetic testing remains inconclusive in ∼7% of the families. 35896117 6 47 theme Project 1128:1134 arg1 data 1136:1139 Genomics England 100,000 Genomes Project data 1095:1139 Genomics England 100,000 Genomes Project data 1095:1139 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 4 48 theme large 529:533 arg1 family 574:579 a large multiplex genetically unresolved (GUR) family 527:579 a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms 527:611 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 10 49 theme PC1 1679:1681 arg1 maturation 1683:1692 PC1 maturation 1679:1692 PC1 maturation 1679:1692 We also show that ALG5 is required for PC1 maturation and membrane and ciliary localization and that heterozygous loss of ALG5 affects PC1 maturation. 35896117 1 50 theme spectrum 175:182 arg1 Disorders 105:113 Disorders 105:113 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum 105:182 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 0 51 theme polycystic 52:61 arg1 disease 70:76 atypical polycystic kidney disease 43:76 atypical polycystic kidney disease 43:76 Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis. 35896117 4 52 theme ADPKD-like 593:602 arg1 symptoms 604:611 ADPKD-like symptoms 593:611 ADPKD-like symptoms 593:611 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 7 53 theme pathogenic 1172:1181 arg1 variants 1183:1190 pathogenic variants 1172:1190 pathogenic variants in ALG5 1172:1198 Four additional families with pathogenic variants in ALG5 were identified. 35896117 6 54 theme Genomics 1095:1102 arg1 data 1136:1139 Genomics England 100,000 Genomes Project data 1095:1139 Genomics England 100,000 Genomes Project data 1095:1139 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 5 55 theme N-glycan 802:809 arg1 precursors 811:820 the assembling N-glycan precursors 787:820 the assembling N-glycan precursors 787:820 ALG5 encodes an endoplasmic-reticulum-resident enzyme required for addition of glucose molecules to the assembling N-glycan precursors. 35896117 2 56 theme major 338:342 arg1 genes 344:348 the two major genes 330:348 the two major genes associated with ADPKD 330:370 PKD1 and PKD2, encoding polycystin (PC)1 and 2, are the two major genes associated with ADPKD; other genes include IFT140, GANAB, DNAJB11, and ALG9. 35896117 2 56 theme major 338:342 arg1 PKD2 287:290 PKD2 287:290 PKD2 287:290 PKD1 and PKD2, encoding polycystin (PC)1 and 2, are the two major genes associated with ADPKD; other genes include IFT140, GANAB, DNAJB11, and ALG9. 35896117 2 56 theme major 338:342 arg1 PKD1 278:281 PKD1 278:281 PKD1 278:281 PKD1 and PKD2, encoding polycystin (PC)1 and 2, are the two major genes associated with ADPKD; other genes include IFT140, GANAB, DNAJB11, and ALG9. 35896117 8 57 theme Clinical 1217:1224 arg1 presentation 1226:1237 Clinical presentation 1217:1237 Clinical presentation 1217:1237 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 11 58 theme function 1892:1899 arg1 decline 1901:1907 kidney function decline 1885:1907 kidney function decline 1885:1907 Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline. 35896117 6 59 theme tubulointerstitial 937:954 arg1 GUR 981:983 GUR 981:983 GUR 981:983 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 59 theme tubulointerstitial 937:954 arg1 diseases 963:970 ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases 900:970 ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD) 900:978 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 59 theme tubulointerstitial 937:954 arg1 naive 998:1002 naive 998:1002 naive 998:1002 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 6 59 theme tubulointerstitial 937:954 arg1 ADTKD 973:977 ADTKD 973:977 ADTKD 973:977 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 1 60 theme autosomal 122:130 arg1 ADPKD 168:172 ADPKD 168:172 ADPKD 168:172 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 1 60 theme autosomal 122:130 arg1 disease 159:165 autosomal dominant polycystic kidney disease 122:165 the autosomal dominant polycystic kidney disease (ADPKD) spectrum 118:182 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 8 61 theme age 1409:1411 arg1 years 1400:1404 62 to 91 years 1391:1404 62 to 91 years of age 1391:1411 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 7 62 with families 1158:1165 arg1 variants 1183:1190 pathogenic variants 1172:1190 pathogenic variants in ALG5 1172:1198 Four additional families with pathogenic variants in ALG5 were identified. 35896117 11 63 theme ALG5 1754:1757 arg1 variants 1742:1749 monoallelic variants 1730:1749 monoallelic variants of ALG5 1730:1757 Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline. 35896117 9 64 theme ALG5 1434:1437 arg1 haploinsufficiency 1439:1456 ALG5 haploinsufficiency 1434:1456 ALG5 haploinsufficiency 1434:1456 We demonstrate that ALG5 haploinsufficiency is sufficient to alter the synthesis of the N-glycan chain in renal epithelial cells. 35896117 7 65 from variants 1183:1190 arg1 ALG5 1195:1198 ALG5 1195:1198 ALG5 1195:1198 Four additional families with pathogenic variants in ALG5 were identified. 35896117 1 66 theme disease 159:165 arg1 spectrum 175:182 the autosomal dominant polycystic kidney disease (ADPKD) spectrum 118:182 the autosomal dominant polycystic kidney disease (ADPKD) spectrum 118:182 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 35896117 4 67 theme frameshift 642:651 arg1 c.703_704delCA 662:675 c.703_704delCA 662:675 c.703_704delCA 662:675 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 4 67 theme frameshift 642:651 arg1 variant 653:659 a monoallelic frameshift variant 628:659 a monoallelic frameshift variant (c.703_704delCA) 628:676 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 7 68 theme additional 1147:1156 arg1 families 1158:1165 Four additional families 1142:1165 Four additional families with pathogenic variants in ALG5 1142:1198 Four additional families with pathogenic variants in ALG5 were identified. 35896117 9 69 from synthesis 1485:1493 arg1 cells 1537:1541 renal epithelial cells 1520:1541 renal epithelial cells 1520:1541 We demonstrate that ALG5 haploinsufficiency is sufficient to alter the synthesis of the N-glycan chain in renal epithelial cells. 35896117 8 70 theme cystic 1300:1305 arg1 kidneys 1307:1313 non-enlarged cystic kidneys 1287:1313 non-enlarged cystic kidneys 1287:1313 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 10 71 theme ciliary 1615:1621 arg1 localization 1623:1634 membrane and ciliary localization 1602:1634 localization 1623:1634 We also show that ALG5 is required for PC1 maturation and membrane and ciliary localization and that heterozygous loss of ALG5 affects PC1 maturation. 35896117 4 72 from sequencing 513:522 arg1 family 574:579 a large multiplex genetically unresolved (GUR) family 527:579 a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms 527:611 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 9 73 theme N-glycan 1502:1509 arg1 chain 1511:1515 the N-glycan chain 1498:1515 the N-glycan chain 1498:1515 We demonstrate that ALG5 haploinsufficiency is sufficient to alter the synthesis of the N-glycan chain in renal epithelial cells. 35896117 11 74 theme kidney 1832:1837 arg1 cysts 1839:1843 multiple small kidney cysts 1817:1843 multiple small kidney cysts 1817:1843 Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline. 35896117 8 75 from members 1273:1279 arg1 consistent 1243:1252 consistent 1243:1252 consistent 1243:1252 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 6 76 theme parallel 1058:1065 arg1 sequencing 1067:1076 targeted massively parallel sequencing 1039:1076 targeted massively parallel sequencing 1039:1076 To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. 35896117 8 77 theme liver 1329:1333 arg1 cysts 1335:1339 few or no liver cysts 1319:1339 few or no liver cysts 1319:1339 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 10 78 theme membrane 1602:1609 arg1 localization 1623:1634 membrane and ciliary localization 1602:1634 localization 1623:1634 We also show that ALG5 is required for PC1 maturation and membrane and ciliary localization and that heterozygous loss of ALG5 affects PC1 maturation. 35896117 0 79 theme atypical 43:50 arg1 disease 70:76 atypical polycystic kidney disease 43:76 atypical polycystic kidney disease 43:76 Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis. 35896117 9 80 theme epithelial 1526:1535 arg1 cells 1537:1541 renal epithelial cells 1520:1541 renal epithelial cells 1520:1541 We demonstrate that ALG5 haploinsufficiency is sufficient to alter the synthesis of the N-glycan chain in renal epithelial cells. 35896117 11 81 theme interstitial 1858:1869 arg1 fibrosis 1871:1878 progressive interstitial fibrosis 1846:1878 progressive interstitial fibrosis 1846:1878 Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline. 35896117 0 82 theme kidney 63:68 arg1 disease 70:76 atypical polycystic kidney disease 43:76 atypical polycystic kidney disease 43:76 Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis. 35896117 8 83 dep 91 1397:1398 arg1 to 1394:1395 to 1394:1395 to 1394:1395 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 4 84 theme unresolved 557:566 arg1 family 574:579 a large multiplex genetically unresolved (GUR) family 527:579 a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms 527:611 We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. 35896117 8 85 theme end-stage 1361:1369 arg1 disease 1378:1384 end-stage kidney disease 1361:1384 end-stage kidney disease 1361:1384 Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. 35896117 3 86 theme Genetic 427:433 arg1 testing 435:441 Genetic testing 427:441 Genetic testing 427:441 Genetic testing remains inconclusive in ∼7% of the families. 35896117 5 87 theme molecules 774:782 arg1 addition 754:761 addition 754:761 addition of glucose molecules to the assembling N-glycan precursors 754:820 ALG5 encodes an endoplasmic-reticulum-resident enzyme required for addition of glucose molecules to the assembling N-glycan precursors. 35896117 1 88 theme kidney 253:258 arg1 decline 269:275 progressive kidney function decline 241:275 progressive kidney function decline 241:275 Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. 37299550 4 0 theme Bifidobacterium 519:533 arg1 subsp 542:546 the probiotic Bifidobacterium longum subsp 505:546 the probiotic Bifidobacterium longum subsp 505:546 In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. 37299550 11 1 theme gut 1096:1098 arg1 composition 1111:1121 The gut microbiota composition 1092:1121 The gut microbiota composition 1092:1121 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 6 2 dep microbiome 666:675 arg1 infantis 563:570 infantis) 563:571 infantis) 563:571 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 4 3 theme subsp 542:546 arg1 effect 495:500 the effect 491:500 the effect of the probiotic Bifidobacterium longum subsp 491:546 In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. 37299550 7 4 dep treatments 801:810 arg1 Donor 845:849 (2) Donor human milk (DHM) 841:866 (2) Donor human milk (DHM) 841:866 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 7 4 dep treatments 801:810 arg1 formula 832:838 (1) Preterm infant formula 813:838 (1) Preterm infant formula 813:838 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 7 4 dep treatments 801:810 arg1 formula 907:913 (4) Infant formula 896:913 (4) Infant formula 896:913 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 7 4 dep treatments 801:810 arg1 BL 917:918 BL 917:918 BL 917:918 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 7 4 dep treatments 801:810 arg1 formula 880:886 (3) Infant formula 869:886 (3) Infant formula 869:886 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 18 5 theme microbial 1777:1785 arg1 species 1787:1793 microbial species 1777:1793 microbial species positively associated with both diet and NEC incidence 1777:1848 The results highlight the differences in microbial species positively associated with both diet and NEC incidence. 37299550 8 6 theme Infant 939:944 arg1 formula 946:952 Infant formula 939:952 Infant formula 939:952 infantis, and (5) Infant formula and BL. 37299550 3 7 from incidence 441:449 arg1 infants 454:460 infants 454:460 infants 454:460 Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. 37299550 2 8 theme microbial 287:295 arg1 colonization 297:308 gut microbial colonization 283:308 gut microbial colonization 283:308 Major risk factors include prematurity, formula feeding, and gut microbial colonization. 37299550 7 9 dep formula 907:913 arg1 4 897:897 4 897:897 4 897:897 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 1 10 theme gastrointestinal 177:192 arg1 disease 194:200 gastrointestinal disease 177:200 gastrointestinal disease in preterm infants 177:219 Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. 37299550 4 11 dep Bifidobacterium 519:533 arg1 longum 535:540 longum 535:540 longum 535:540 In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. 37299550 1 12 from disease 194:200 arg1 infants 213:219 preterm infants 205:219 preterm infants 205:219 Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. 37299550 0 13 from Microbiome 59:68 arg1 Pigs 99:102 Preterm Pigs 91:102 Preterm Pigs 91:102 Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs. 37299550 14 14 theme BL 1387:1388 arg1 abundance 1374:1382 The abundance 1370:1382 The abundance of BL. 1370:1389 The abundance of BL. 37299550 16 15 from abundant 1545:1552 arg1 NEC 1557:1559 NEC 1557:1559 NEC 1557:1559 Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. 37299550 11 16 theme rectal 1211:1216 arg1 samples 1224:1230 rectal stool samples 1211:1230 rectal stool samples 1211:1230 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 6 17 theme human 606:610 arg1 -on 658:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 15 18 theme disease 1447:1453 arg1 severity 1455:1462 disease severity 1447:1462 disease severity 1447:1462 infantis in the gut contents negatively correlated with disease severity. 37299550 2 19 theme risk 228:231 arg1 factors 233:239 Major risk factors 222:239 Major risk factors 222:239 Major risk factors include prematurity, formula feeding, and gut microbial colonization. 37299550 11 20 theme intestinal 1236:1245 arg1 contents 1247:1254 intestinal contents 1236:1254 intestinal contents 1236:1254 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 0 21 theme NEC 74:76 arg1 Incidence 78:86 NEC Incidence 74:86 NEC Incidence 74:86 Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs. 37299550 1 22 theme leading 144:150 arg1 cause 152:156 the leading cause 140:156 the leading cause of death caused by gastrointestinal disease in preterm infants 140:219 Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. 37299550 1 22 theme leading 144:150 arg1 enterocolitis 117:129 Necrotizing enterocolitis 105:129 Necrotizing enterocolitis (NEC) 105:135 Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. 37299550 3 23 attach linked 330:335 arg1 NEC 340:342 NEC 340:342 NEC 340:342 Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. 37299550 3 23 attach linked 330:335 arg2 Microbes 311:318 Microbes 311:318 Microbes 311:318 Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. 37299550 6 24 with combination 587:597 arg1 -on 658:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 11 25 theme contents 1247:1254 arg1 WGS 1203:1205 WGS 1203:1205 WGS 1203:1205 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 11 25 theme contents 1247:1254 arg1 sequencing 1191:1200 16S and whole-genome sequencing 1170:1200 sequencing 1191:1200 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 11 26 theme samples 1224:1230 arg1 WGS 1203:1205 WGS 1203:1205 WGS 1203:1205 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 11 26 theme samples 1224:1230 arg1 sequencing 1191:1200 16S and whole-genome sequencing 1170:1200 sequencing 1191:1200 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 7 27 theme infant 825:830 arg1 formula 832:838 (1) Preterm infant formula 813:838 (1) Preterm infant formula 813:838 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 12 28 theme Dietary 1257:1263 arg1 BL 1265:1266 Dietary BL 1257:1266 Dietary BL. 1257:1267 Dietary BL. 37299550 6 29 theme HMO 634:636 arg1 -on 658:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 3 30 theme select 393:398 arg1 probiotics 400:409 select probiotics 393:409 select probiotics 393:409 Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. 37299550 6 31 theme oligosaccharide 617:631 arg1 -on 658:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 16 32 theme sensu 1477:1481 arg1 stricto 1483:1489 Clostridium sensu stricto 1 1465:1491 Clostridium sensu stricto 1 1465:1491 Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. 37299550 10 33 from segments 1066:1073 arg1 tissue 1046:1051 tissue 1046:1051 tissue from all the segments of the GI tract 1046:1089 NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. 37299550 10 33 from segments 1066:1073 arg1 evaluation 1032:1041 the evaluation 1028:1041 the evaluation of tissue from all the segments of the GI tract 1028:1089 NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. 37299550 10 34 theme tissue 1046:1051 arg1 evaluation 1032:1041 the evaluation 1028:1041 the evaluation of tissue from all the segments of the GI tract 1028:1089 NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. 37299550 0 35 theme Human 15:19 arg1 Milk 21:24 Human Milk 15:24 Human Milk 15:24 Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs. 37299550 0 36 dep Microbiome 59:68 arg1 the 51:53 the 51:53 the 51:53 Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs. 37299550 3 37 theme causal 373:378 arg1 species 380:386 causal species 373:386 causal species 373:386 Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. 37299550 13 38 theme NEC 1365:1367 arg1 incidence 1352:1360 the incidence 1348:1360 the incidence of NEC 1348:1367 infantis and 3'SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. 37299550 11 39 theme whole-genome 1178:1189 arg1 WGS 1203:1205 WGS 1203:1205 WGS 1203:1205 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 11 39 theme whole-genome 1178:1189 arg1 sequencing 1191:1200 16S and whole-genome sequencing 1170:1200 sequencing 1191:1200 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 18 40 from differences 1762:1772 arg1 species 1787:1793 microbial species 1777:1793 microbial species positively associated with both diet and NEC incidence 1777:1848 The results highlight the differences in microbial species positively associated with both diet and NEC incidence. 37299550 16 41 theme Clostridium 1497:1507 arg1 perfringens 1509:1519 Clostridium perfringens 1497:1519 Clostridium perfringens 1497:1519 Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. 37299550 6 42 from incidence 686:694 arg1 piglets 714:720 preterm piglets 706:720 preterm piglets 706:720 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 6 43 theme formula 736:742 arg1 diet 744:747 an infant formula diet 726:747 an infant formula diet 726:747 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 1 44 theme preterm 205:211 arg1 infants 213:219 preterm infants 205:219 preterm infants 205:219 Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. 37299550 11 45 theme microbiota 1100:1109 arg1 composition 1111:1121 The gut microbiota composition 1092:1121 The gut microbiota composition 1092:1121 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 10 46 theme tract 1085:1089 arg1 segments 1066:1073 all the segments 1058:1073 all the segments of the GI tract 1058:1089 NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. 37299550 7 47 theme Infant 900:905 arg1 formula 907:913 (4) Infant formula 896:913 (4) Infant formula 896:913 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 6 48 theme -sialylactose 638:650 arg1 -on 658:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 4 49 theme probiotic 509:517 arg1 subsp 542:546 the probiotic Bifidobacterium longum subsp 505:546 the probiotic Bifidobacterium longum subsp 505:546 In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. 37299550 6 50 theme preterm 706:712 arg1 piglets 714:720 preterm piglets 706:720 preterm piglets 706:720 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 7 51 theme preterm 764:770 arg1 piglets 772:778 50 preterm piglets 761:778 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL 761:918 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 17 52 theme formula-based 1716:1728 arg1 diet 1730:1733 an exclusively formula-based diet 1701:1733 an exclusively formula-based diet 1701:1733 Our results suggest that pre- and probiotics are not sufficient for protection from NEC in an exclusively formula-based diet. 37299550 6 53 theme NEC 699:701 arg1 incidence 686:694 the incidence 682:694 the incidence of NEC in preterm piglets 682:720 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 2 54 theme formula 262:268 arg1 feeding 270:276 formula feeding 262:276 formula feeding 262:276 Major risk factors include prematurity, formula feeding, and gut microbial colonization. 37299550 16 55 theme disease 1592:1598 arg1 severity 1600:1607 disease severity 1592:1607 disease severity 1592:1607 Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. 37299550 1 56 theme death 161:165 arg1 cause 152:156 the leading cause 140:156 the leading cause of death caused by gastrointestinal disease in preterm infants 140:219 Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. 37299550 1 56 theme death 161:165 arg1 enterocolitis 117:129 Necrotizing enterocolitis 105:129 Necrotizing enterocolitis (NEC) 105:135 Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. 37299550 16 57 from NEC 1557:1559 arg1 abundant 1545:1552 abundant 1545:1552 abundant 1545:1552 Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. 37299550 2 58 theme gut 283:285 arg1 colonization 297:308 gut microbial colonization 283:308 gut microbial colonization 283:308 Major risk factors include prematurity, formula feeding, and gut microbial colonization. 37299550 13 59 theme SL 1284:1285 arg1 supplementation 1287:1301 3'SL supplementation 1282:1301 3'SL supplementation 1282:1301 infantis and 3'SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. 37299550 0 60 from Incidence 78:86 arg1 Pigs 99:102 Preterm Pigs 91:102 Preterm Pigs 91:102 Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs. 37299550 7 61 theme Infant 873:878 arg1 formula 880:886 (3) Infant formula 869:886 (3) Infant formula 869:886 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 15 62 theme gut 1407:1409 arg1 contents 1411:1418 the gut contents 1403:1418 the gut contents 1403:1418 infantis in the gut contents negatively correlated with disease severity. 37299550 2 63 theme Major 222:226 arg1 factors 233:239 Major risk factors 222:239 Major risk factors 222:239 Major risk factors include prematurity, formula feeding, and gut microbial colonization. 37299550 1 64 theme Necrotizing 105:115 arg1 cause 152:156 the leading cause 140:156 the leading cause of death caused by gastrointestinal disease in preterm infants 140:219 Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. 37299550 1 64 theme Necrotizing 105:115 arg1 NEC 132:134 NEC 132:134 NEC 132:134 Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. 37299550 1 64 theme Necrotizing 105:115 arg1 enterocolitis 117:129 Necrotizing enterocolitis 105:129 Necrotizing enterocolitis (NEC) 105:135 Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. 37299550 10 65 from evaluation 1032:1041 arg1 segments 1066:1073 all the segments 1058:1073 all the segments of the GI tract 1058:1089 NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. 37299550 18 66 dep diet 1827:1830 arg1 incidence 1840:1848 incidence 1840:1848 incidence 1840:1848 The results highlight the differences in microbial species positively associated with both diet and NEC incidence. 37299550 17 67 from NEC 1694:1696 arg1 protection 1678:1687 protection 1678:1687 protection from NEC in an exclusively formula-based diet 1678:1733 Our results suggest that pre- and probiotics are not sufficient for protection from NEC in an exclusively formula-based diet. 37299550 7 68 theme human 851:855 arg1 DHM 863:865 DHM 863:865 DHM 863:865 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 7 68 theme human 851:855 arg1 milk 857:860 human milk 851:860 (2) Donor human milk (DHM) 841:866 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 7 69 dep formula 832:838 arg1 1 814:814 1 814:814 1 814:814 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 17 70 from protection 1678:1687 arg1 diet 1730:1733 an exclusively formula-based diet 1701:1733 an exclusively formula-based diet 1701:1733 Our results suggest that pre- and probiotics are not sufficient for protection from NEC in an exclusively formula-based diet. 37299550 11 71 theme stool 1218:1222 arg1 samples 1224:1230 rectal stool samples 1211:1230 rectal stool samples 1211:1230 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 0 72 theme Preterm 91:97 arg1 Pigs 99:102 Preterm Pigs 91:102 Preterm Pigs 91:102 Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs. 37299550 10 73 dep NEC 979:981 arg1 incidence 983:991 incidence 983:991 incidence 983:991 NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. 37299550 10 73 dep NEC 979:981 arg1 NEC 979:981 NEC incidence and severity 979:1004 NEC incidence and severity 979:1004 NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. 37299550 10 73 dep NEC 979:981 arg1 severity 997:1004 severity 997:1004 severity 997:1004 NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. 37299550 7 74 theme Preterm 817:823 arg1 formula 832:838 (1) Preterm infant formula 813:838 (1) Preterm infant formula 813:838 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 6 75 theme milk 612:615 arg1 -on 658:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 16 76 theme Clostridium 1465:1475 arg1 stricto 1483:1489 Clostridium sensu stricto 1 1465:1491 Clostridium sensu stricto 1 1465:1491 Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. 37299550 6 77 theme 3'SL 653:656 arg1 -on 658:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on 604:660 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 7 78 dep Donor 845:849 arg1 2 842:842 2 842:842 2 842:842 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 7 78 dep Donor 845:849 arg1 DHM 863:865 DHM 863:865 DHM 863:865 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 7 78 dep Donor 845:849 arg1 milk 857:860 human milk 851:860 (2) Donor human milk (DHM) 841:866 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 13 79 contain had 1303:1305 arg1 supplementation 1287:1301 3'SL supplementation 1282:1301 3'SL supplementation 1282:1301 infantis and 3'SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. 37299550 13 79 contain had 1303:1305 arg1 infantis 1269:1276 infantis 1269:1276 infantis 1269:1276 infantis and 3'SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. 37299550 13 79 contain had 1303:1305 arg2 effect 1310:1315 no effect 1307:1315 no effect 1307:1315 infantis and 3'SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. 37299550 11 80 theme 16S 1170:1172 arg1 WGS 1203:1205 WGS 1203:1205 WGS 1203:1205 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 11 80 theme 16S 1170:1172 arg1 sequencing 1191:1200 16S and whole-genome sequencing 1170:1200 sequencing 1191:1200 The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. 37299550 3 81 theme species 380:386 arg1 evidence 361:368 no evidence 358:368 no evidence of causal species 358:386 Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. 37299550 0 82 theme Gut 55:57 arg1 Microbiome 59:68 Gut Microbiome 55:68 Gut Microbiome 55:68 Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs. 37299550 8 83 dep formula 946:952 arg1 5 936:936 5 936:936 5 936:936 infantis, and (5) Infant formula and BL. 37299550 6 84 theme infant 729:734 arg1 diet 744:747 an infant formula diet 726:747 an infant formula diet 726:747 infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. 37299550 3 85 theme NEC 437:439 arg1 incidence 441:449 NEC incidence 437:449 NEC incidence in infants 437:460 Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. 37299550 5 86 dep infantis 549:556 arg1 BL 559:560 BL 559:560 BL 559:560 infantis (BL. 37299550 7 87 dep formula 880:886 arg1 3 870:870 3 870:870 3 870:870 We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. 37299550 10 88 theme GI 1082:1083 arg1 tract 1085:1089 the GI tract 1078:1089 the GI tract 1078:1089 NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. 37299550 15 89 from infantis 1391:1398 arg1 contents 1411:1418 the gut contents 1403:1418 the gut contents 1403:1418 infantis in the gut contents negatively correlated with disease severity. 36941311 5 0 from OGT 838:840 arg1 dimer 793:797 an antiparallel dimer 777:797 an antiparallel dimer instead of the X-shaped dimer in human OGT 777:840 SPY forms an antiparallel dimer instead of the X-shaped dimer in human OGT, and its catalytic domain interconverts among multiple conformations. 36941311 6 1 theme mass 924:927 arg1 spectrometry 929:940 mass spectrometry 924:940 mass spectrometry 924:940 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 2 2 theme catalytic 374:382 arg1 domain 384:389 a C-terminal catalytic domain 361:389 a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs) 361:462 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 6 3 dep demonstrates 998:1009 arg1 whereas 1129:1135 whereas 1129:1135 whereas 1129:1135 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 5 4 theme X-shaped 814:821 arg1 dimer 823:827 the X-shaped dimer 810:827 the X-shaped dimer in human OGT 810:840 SPY forms an antiparallel dimer instead of the X-shaped dimer in human OGT, and its catalytic domain interconverts among multiple conformations. 36941311 5 5 from dimer 823:827 arg1 OGT 838:840 human OGT 832:840 human OGT 832:840 SPY forms an antiparallel dimer instead of the X-shaped dimer in human OGT, and its catalytic domain interconverts among multiple conformations. 36941311 2 6 theme C-terminal 363:372 arg1 domain 384:389 a C-terminal catalytic domain 361:389 a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs) 361:462 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 6 7 contain contains 1057:1064 arg2 sites 1090:1094 trans auto-fucosylation sites 1066:1094 trans auto-fucosylation sites 1066:1094 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 6 7 contain contains 1057:1064 arg1 peptide 1042:1048 the N-terminal disordered peptide 1016:1048 the N-terminal disordered peptide in SPY 1016:1055 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 1 8 from SPINDLY 72:78 arg1 thaliana 101:108 Arabidopsis thaliana 89:108 Arabidopsis thaliana 89:108 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 6 9 theme co-IP 943:947 arg1 Analysis 912:919 Analysis 912:919 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data 912:988 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 6 10 theme disordered 1031:1040 arg1 peptide 1042:1048 the N-terminal disordered peptide 1016:1048 the N-terminal disordered peptide in SPY 1016:1055 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 5 11 theme antiparallel 780:791 arg1 dimer 793:797 an antiparallel dimer 777:797 an antiparallel dimer instead of the X-shaped dimer in human OGT 777:840 SPY forms an antiparallel dimer instead of the X-shaped dimer in human OGT, and its catalytic domain interconverts among multiple conformations. 36941311 4 12 theme binding 758:764 arg1 GDP-fucose 725:734 GDP-fucose 725:734 GDP-fucose instead of UDP-GlcNAc binding 725:764 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 36941311 6 13 from peptide 1042:1048 arg1 SPY 1053:1055 SPY 1053:1055 SPY 1053:1055 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 2 14 theme GlcNAc 436:441 arg1 transferases 444:455 the O-linked-N-acetylglucosamine (GlcNAc) transferases 402:455 the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs) 402:462 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 2 14 theme GlcNAc 436:441 arg1 OGTs 458:461 OGTs 458:461 OGTs 458:461 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 6 15 theme spectrometry 929:940 arg1 Analysis 912:919 Analysis 912:919 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data 912:988 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 5 16 theme dimer 823:827 arg1 dimer 793:797 an antiparallel dimer 777:797 an antiparallel dimer instead of the X-shaped dimer in human OGT 777:840 SPY forms an antiparallel dimer instead of the X-shaped dimer in human OGT, and its catalytic domain interconverts among multiple conformations. 36941311 6 17 theme substrate 1208:1216 arg1 binding 1218:1224 protein substrate binding 1200:1224 protein substrate binding 1200:1224 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 2 18 theme ER-localized 280:291 arg1 POFUTs 293:298 ER-localized POFUTs 280:298 ER-localized POFUTs 280:298 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 4 19 theme cryo-electron 591:603 arg1 cryo-EM 617:623 cryo-EM 617:623 cryo-EM 617:623 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 36941311 4 19 theme cryo-electron 591:603 arg1 microscopy 605:614 cryo-electron microscopy 591:614 the cryo-electron microscopy (cryo-EM) structure of SPY 587:641 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 36941311 2 20 theme O-linked-N-acetylglucosamine 406:433 arg1 transferases 444:455 the O-linked-N-acetylglucosamine (GlcNAc) transferases 402:455 the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs) 402:462 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 2 20 theme O-linked-N-acetylglucosamine 406:433 arg1 OGTs 458:461 OGTs 458:461 OGTs 458:461 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 6 21 theme fucosylation 950:961 arg1 activity 963:970 fucosylation activity 950:970 fucosylation activity 950:970 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 6 22 theme N-terminal 1020:1029 arg1 peptide 1042:1048 the N-terminal disordered peptide 1016:1048 the N-terminal disordered peptide in SPY 1016:1055 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 4 23 theme active-site 695:705 arg1 features 707:714 distinct active-site features 686:714 distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding 686:764 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 36941311 2 24 theme tetratricopeptide 324:340 arg1 TPRs 351:354 TPRs 351:354 TPRs 351:354 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 2 24 theme tetratricopeptide 324:340 arg1 repeats 342:348 N-terminal tetratricopeptide repeats 313:348 N-terminal tetratricopeptide repeats (TPRs) 313:355 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 1 25 theme diverse 193:199 arg1 processes 215:223 diverse developmental processes 193:223 diverse developmental processes 193:223 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 5 26 theme catalytic 851:859 arg1 domain 861:866 its catalytic domain 847:866 its catalytic domain 847:866 SPY forms an antiparallel dimer instead of the X-shaped dimer in human OGT, and its catalytic domain interconverts among multiple conformations. 36941311 4 27 theme microscopy 605:614 arg1 structure 626:634 the cryo-electron microscopy (cryo-EM) structure 587:634 the cryo-electron microscopy (cryo-EM) structure of SPY 587:641 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 36941311 2 28 theme N-terminal 313:322 arg1 TPRs 351:354 TPRs 351:354 TPRs 351:354 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 2 28 theme N-terminal 313:322 arg1 repeats 342:348 N-terminal tetratricopeptide repeats 313:348 N-terminal tetratricopeptide repeats (TPRs) 313:355 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 6 29 theme activity 963:970 arg1 Analysis 912:919 Analysis 912:919 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data 912:988 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 1 30 theme developmental 201:213 arg1 processes 215:223 diverse developmental processes 193:223 diverse developmental processes 193:223 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 0 31 theme Arabidopsis 30:40 arg1 O-fucosyltransferase 42:61 the Arabidopsis O-fucosyltransferase 26:61 the Arabidopsis O-fucosyltransferase 26:61 Structure and dynamics of the Arabidopsis O-fucosyltransferase SPINDLY. 36941311 2 32 contain contains 304:311 arg2 TPRs 351:354 TPRs 351:354 TPRs 351:354 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 2 32 contain contains 304:311 arg2 domain 384:389 a C-terminal catalytic domain 361:389 a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs) 361:462 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 2 32 contain contains 304:311 arg2 repeats 342:348 N-terminal tetratricopeptide repeats 313:348 N-terminal tetratricopeptide repeats (TPRs) 313:355 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 2 32 contain contains 304:311 arg1 SPY 259:261 SPY 259:261 SPY 259:261 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 5 33 from dimer 793:797 arg1 OGT 838:840 human OGT 832:840 human OGT 832:840 SPY forms an antiparallel dimer instead of the X-shaped dimer in human OGT, and its catalytic domain interconverts among multiple conformations. 36941311 4 34 theme distinct 686:693 arg1 features 707:714 distinct active-site features 686:714 distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding 686:764 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 36941311 5 35 theme multiple 888:895 arg1 conformations 897:909 multiple conformations 888:909 multiple conformations 888:909 SPY forms an antiparallel dimer instead of the X-shaped dimer in human OGT, and its catalytic domain interconverts among multiple conformations. 36941311 3 36 theme structural 478:487 arg1 feature 489:495 the structural feature 474:495 the structural feature that determines the distinct enzymatic selectivity of SPY 474:553 However, the structural feature that determines the distinct enzymatic selectivity of SPY remains unknown. 36941311 5 37 theme human 832:836 arg1 OGT 838:840 human OGT 832:840 human OGT 832:840 SPY forms an antiparallel dimer instead of the X-shaped dimer in human OGT, and its catalytic domain interconverts among multiple conformations. 36941311 6 38 theme data 985:988 arg1 Analysis 912:919 Analysis 912:919 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data 912:988 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 6 39 theme SPY 1167:1169 arg1 activity 1171:1178 SPY activity 1167:1178 SPY activity 1167:1178 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 3 40 theme distinct 517:524 arg1 selectivity 536:546 the distinct enzymatic selectivity 513:546 the distinct enzymatic selectivity of SPY 513:553 However, the structural feature that determines the distinct enzymatic selectivity of SPY remains unknown. 36941311 0 41 theme O-fucosyltransferase 42:61 arg1 dynamics 14:21 dynamics 14:21 dynamics 14:21 Structure and dynamics of the Arabidopsis O-fucosyltransferase SPINDLY. 36941311 0 41 theme O-fucosyltransferase 42:61 arg1 Structure 0:8 Structure 0:8 Structure 0:8 Structure and dynamics of the Arabidopsis O-fucosyltransferase SPINDLY. 36941311 6 42 theme cryo-EM 977:983 arg1 data 985:988 cryo-EM data 977:988 cryo-EM data 977:988 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 2 43 theme Sequence 226:233 arg1 analysis 235:242 Sequence analysis 226:242 Sequence analysis 226:242 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 3 44 theme enzymatic 526:534 arg1 selectivity 536:546 the distinct enzymatic selectivity 513:546 the distinct enzymatic selectivity of SPY 513:553 However, the structural feature that determines the distinct enzymatic selectivity of SPY remains unknown. 36941311 2 45 from POFUTs 293:298 arg1 distinct 266:273 distinct 266:273 distinct 266:273 Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetratricopeptide repeats (TPRs) and a C-terminal catalytic domain resembling the O-linked-N-acetylglucosamine (GlcNAc) transferases (OGTs). 36941311 1 46 theme protein 139:145 arg1 O-fucosyltransferase 147:166 a novel nucleocytoplasmic protein O-fucosyltransferase 113:166 a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT) 113:174 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 1 46 theme protein 139:145 arg1 SPINDLY 72:78 SPINDLY 72:78 SPINDLY (SPY) in Arabidopsis thaliana 72:108 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 1 46 theme protein 139:145 arg1 POFUT 169:173 POFUT 169:173 POFUT 169:173 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 4 47 with structure 626:634 arg1 GDP-fucose 664:673 GDP-fucose 664:673 GDP-fucose 664:673 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 36941311 1 48 theme novel 115:119 arg1 O-fucosyltransferase 147:166 a novel nucleocytoplasmic protein O-fucosyltransferase 113:166 a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT) 113:174 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 1 48 theme novel 115:119 arg1 SPINDLY 72:78 SPINDLY 72:78 SPINDLY (SPY) in Arabidopsis thaliana 72:108 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 1 48 theme novel 115:119 arg1 POFUT 169:173 POFUT 169:173 POFUT 169:173 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 1 49 theme Arabidopsis 89:99 arg1 thaliana 101:108 Arabidopsis thaliana 89:108 Arabidopsis thaliana 89:108 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 4 50 theme SPY 639:641 arg1 complex 651:657 its complex 647:657 its complex with GDP-fucose 647:673 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 36941311 4 50 theme SPY 639:641 arg1 structure 626:634 the cryo-electron microscopy (cryo-EM) structure 587:634 the cryo-electron microscopy (cryo-EM) structure of SPY 587:641 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 36941311 6 51 dep TPRs 1137:1140 arg1 1-5 1142:1144 1-5 1142:1144 1-5 1142:1144 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 6 52 gly auto-fucosylation 1072:1088 arg2 sites 1090:1094 trans auto-fucosylation sites 1066:1094 trans auto-fucosylation sites 1066:1094 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 1 53 theme nucleocytoplasmic 121:137 arg1 O-fucosyltransferase 147:166 a novel nucleocytoplasmic protein O-fucosyltransferase 113:166 a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT) 113:174 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 1 53 theme nucleocytoplasmic 121:137 arg1 SPINDLY 72:78 SPINDLY 72:78 SPINDLY (SPY) in Arabidopsis thaliana 72:108 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 1 53 theme nucleocytoplasmic 121:137 arg1 POFUT 169:173 POFUT 169:173 POFUT 169:173 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. 36941311 6 54 theme auto-fucosylation 1072:1088 arg1 sites 1090:1094 trans auto-fucosylation sites 1066:1094 trans auto-fucosylation sites 1066:1094 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 4 55 with complex 651:657 arg1 GDP-fucose 664:673 GDP-fucose 664:673 GDP-fucose 664:673 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 36941311 6 56 theme POFUT 1113:1117 arg1 activity 1119:1126 the POFUT activity 1109:1126 the POFUT activity 1109:1126 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 3 57 theme SPY 551:553 arg1 selectivity 536:546 the distinct enzymatic selectivity 513:546 the distinct enzymatic selectivity of SPY 513:553 However, the structural feature that determines the distinct enzymatic selectivity of SPY remains unknown. 36941311 6 58 theme trans 1066:1070 arg1 sites 1090:1094 trans auto-fucosylation sites 1066:1094 trans auto-fucosylation sites 1066:1094 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 6 59 theme protein 1200:1206 arg1 binding 1218:1224 protein substrate binding 1200:1224 protein substrate binding 1200:1224 Analysis of mass spectrometry, co-IP, fucosylation activity, and cryo-EM data further demonstrates that the N-terminal disordered peptide in SPY contains trans auto-fucosylation sites and inhibits the POFUT activity, whereas TPRs 1-5 dynamically regulate SPY activity by interfering with protein substrate binding. 36941311 4 60 theme UDP-GlcNAc 747:756 arg1 binding 758:764 UDP-GlcNAc binding 747:764 UDP-GlcNAc binding 747:764 Here we report the cryo-electron microscopy (cryo-EM) structure of SPY and its complex with GDP-fucose, revealing distinct active-site features enabling GDP-fucose instead of UDP-GlcNAc binding. 34995415 9 0 theme pan-caspase 1441:1451 arg1 inhibitor 1453:1461 pan-caspase inhibitor 1441:1461 pan-caspase inhibitor 1441:1461 In contrast, treatment with pan-caspase inhibitor, Q-VD-OPh, does not induce cellular autophagy. 34995415 9 0 theme pan-caspase 1441:1451 arg1 Q-VD-OPh 1464:1471 Q-VD-OPh 1464:1471 Q-VD-OPh 1464:1471 In contrast, treatment with pan-caspase inhibitor, Q-VD-OPh, does not induce cellular autophagy. 34995415 6 1 theme proteomic 944:952 arg1 analysis 954:961 mass spectrometry-based proteomic analysis 920:961 mass spectrometry-based proteomic analysis 920:961 Enrichment of autophagosomes by immunoprecipitation (IP) and mass spectrometry-based proteomic analysis reveals comparable autophagosomal protein content. 34995415 1 2 theme peptide 158:164 arg1 Z-VAD-fmk 124:132 The polycaspase inhibitor Z-VAD-fmk 98:132 The polycaspase inhibitor Z-VAD-fmk 98:132 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 1 2 theme peptide 158:164 arg1 endoglycosidase 191:205 an endoglycosidase 188:205 an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD) 188:340 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 1 2 theme peptide 158:164 arg1 inhibitor 145:153 an inhibitor 142:153 an inhibitor of peptide: N-glycanase (NGLY1) 142:185 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 8 3 theme NGLY1 1287:1291 arg1 inhibition 1293:1302 NGLY1 inhibition 1287:1302 NGLY1 inhibition 1287:1302 Upregulation of autophagy represents a cellular adaptation to NGLY1 inhibition or KD, and ATG13-deficient mouse embryonic fibroblasts (MEFs) show reduced viability under these conditions. 34995415 9 4 theme cellular 1490:1497 arg1 autophagy 1499:1507 cellular autophagy 1490:1507 cellular autophagy 1490:1507 In contrast, treatment with pan-caspase inhibitor, Q-VD-OPh, does not induce cellular autophagy. 34995415 0 5 theme cellular 78:85 arg1 autophagy 87:95 cellular autophagy 78:95 cellular autophagy 78:95 Off-target inhibition of NGLY1 by the polycaspase inhibitor Z-VAD-fmk induces cellular autophagy. 34995415 6 6 theme spectrometry-based 925:942 arg1 analysis 954:961 mass spectrometry-based proteomic analysis 920:961 mass spectrometry-based proteomic analysis 920:961 Enrichment of autophagosomes by immunoprecipitation (IP) and mass spectrometry-based proteomic analysis reveals comparable autophagosomal protein content. 34995415 7 7 theme protein 1196:1202 arg1 disassembly 1212:1222 protein complex disassembly 1196:1222 protein complex disassembly 1196:1222 Gene ontology analysis of proteins enriched in autophagosome IPs shows overrepresentation of factors involved in protein translation, localization and targeting, RNA degradation and protein complex disassembly. 34995415 7 8 theme Gene 1014:1017 arg1 ontology 1019:1026 Gene ontology 1014:1026 Gene ontology analysis of proteins enriched in autophagosome IPs 1014:1077 Gene ontology analysis of proteins enriched in autophagosome IPs shows overrepresentation of factors involved in protein translation, localization and targeting, RNA degradation and protein complex disassembly. 34995415 3 9 theme ER 510:511 arg1 markers 520:526 ER stress markers 510:526 ER stress markers 510:526 The activation of ER stress markers or induction of reactive oxygen species (ROS) is not observed under either condition. 34995415 5 10 theme pharmacological 722:736 arg1 inhibition 744:753 pharmacological NGLY1 inhibition 722:753 pharmacological NGLY1 inhibition 722:753 Under conditions of pharmacological NGLY1 inhibition or NGLY1 KD, upregulation of autophagosome formation without impairment of autophagic flux is observed. 34995415 7 11 theme RNA 1176:1178 arg1 degradation 1180:1190 RNA degradation 1176:1190 RNA degradation 1176:1190 Gene ontology analysis of proteins enriched in autophagosome IPs shows overrepresentation of factors involved in protein translation, localization and targeting, RNA degradation and protein complex disassembly. 34995415 7 12 theme ontology 1019:1026 arg1 analysis 1028:1035 Gene ontology analysis 1014:1035 Gene ontology analysis of proteins enriched in autophagosome IPs 1014:1077 Gene ontology analysis of proteins enriched in autophagosome IPs shows overrepresentation of factors involved in protein translation, localization and targeting, RNA degradation and protein complex disassembly. 34995415 10 13 theme caspase 1673:1679 arg1 inhibitor 1681:1689 an alternative caspase inhibitor 1658:1689 an alternative caspase inhibitor free from this limitation 1658:1715 Therefore, experiments with Z-VAD-fmk are complicated by the effects of NGLY1 inhibition, including induction of autophagy, and Q-VD-OPh represents an alternative caspase inhibitor free from this limitation. 34995415 3 14 theme species 560:566 arg1 activation 496:505 The activation 492:505 The activation of ER stress markers 492:526 The activation of ER stress markers or induction of reactive oxygen species (ROS) is not observed under either condition. 34995415 3 14 theme species 560:566 arg1 induction 531:539 induction 531:539 induction of reactive oxygen species (ROS) 531:572 The activation of ER stress markers or induction of reactive oxygen species (ROS) is not observed under either condition. 34995415 5 15 theme NGLY1 738:742 arg1 inhibition 744:753 pharmacological NGLY1 inhibition 722:753 pharmacological NGLY1 inhibition 722:753 Under conditions of pharmacological NGLY1 inhibition or NGLY1 KD, upregulation of autophagosome formation without impairment of autophagic flux is observed. 34995415 3 16 theme reactive 544:551 arg1 species 560:566 reactive oxygen species 544:566 reactive oxygen species (ROS) 544:572 The activation of ER stress markers or induction of reactive oxygen species (ROS) is not observed under either condition. 34995415 3 16 theme reactive 544:551 arg1 ROS 569:571 ROS 569:571 ROS 569:571 The activation of ER stress markers or induction of reactive oxygen species (ROS) is not observed under either condition. 34995415 6 17 theme comparable 971:980 arg1 content 1005:1011 comparable autophagosomal protein content 971:1011 comparable autophagosomal protein content 971:1011 Enrichment of autophagosomes by immunoprecipitation (IP) and mass spectrometry-based proteomic analysis reveals comparable autophagosomal protein content. 34995415 2 18 theme pharmacological 348:362 arg1 inhibition 376:385 pharmacological N-glycanase inhibition 348:385 pharmacological N-glycanase inhibition by Z-VAD-fmk 348:398 Both pharmacological N-glycanase inhibition by Z-VAD-fmk and siRNA-mediated knockdown (KD) of NGLY1 induce GFP-LC3-positive puncta in HEK 293 cells. 34995415 10 19 with experiments 1521:1531 arg1 Z-VAD-fmk 1538:1546 Z-VAD-fmk 1538:1546 Z-VAD-fmk 1538:1546 Therefore, experiments with Z-VAD-fmk are complicated by the effects of NGLY1 inhibition, including induction of autophagy, and Q-VD-OPh represents an alternative caspase inhibitor free from this limitation. 34995415 4 20 theme intracellular 680:692 arg1 stores 694:699 intracellular stores 680:699 intracellular stores 680:699 Moreover, Ca2+ handling is unaffected when observing release from intracellular stores. 34995415 8 21 theme reduced 1371:1377 arg1 viability 1379:1387 reduced viability 1371:1387 reduced viability 1371:1387 Upregulation of autophagy represents a cellular adaptation to NGLY1 inhibition or KD, and ATG13-deficient mouse embryonic fibroblasts (MEFs) show reduced viability under these conditions. 34995415 2 22 theme siRNA-mediated 404:417 arg1 KD 430:431 KD 430:431 KD 430:431 Both pharmacological N-glycanase inhibition by Z-VAD-fmk and siRNA-mediated knockdown (KD) of NGLY1 induce GFP-LC3-positive puncta in HEK 293 cells. 34995415 2 22 theme siRNA-mediated 404:417 arg1 knockdown 419:427 siRNA-mediated knockdown 404:427 siRNA-mediated knockdown (KD) of NGLY1 404:441 Both pharmacological N-glycanase inhibition by Z-VAD-fmk and siRNA-mediated knockdown (KD) of NGLY1 induce GFP-LC3-positive puncta in HEK 293 cells. 34995415 10 23 from limitation 1706:1715 arg1 free 1691:1694 free 1691:1694 free 1691:1694 Therefore, experiments with Z-VAD-fmk are complicated by the effects of NGLY1 inhibition, including induction of autophagy, and Q-VD-OPh represents an alternative caspase inhibitor free from this limitation. 34995415 9 24 with treatment 1426:1434 arg1 inhibitor 1453:1461 pan-caspase inhibitor 1441:1461 pan-caspase inhibitor 1441:1461 In contrast, treatment with pan-caspase inhibitor, Q-VD-OPh, does not induce cellular autophagy. 34995415 9 24 with treatment 1426:1434 arg1 Q-VD-OPh 1464:1471 Q-VD-OPh 1464:1471 Q-VD-OPh 1464:1471 In contrast, treatment with pan-caspase inhibitor, Q-VD-OPh, does not induce cellular autophagy. 34995415 8 25 theme cellular 1264:1271 arg1 adaptation 1273:1282 a cellular adaptation 1262:1282 a cellular adaptation to NGLY1 inhibition or KD 1262:1308 Upregulation of autophagy represents a cellular adaptation to NGLY1 inhibition or KD, and ATG13-deficient mouse embryonic fibroblasts (MEFs) show reduced viability under these conditions. 34995415 5 26 theme inhibition 744:753 arg1 conditions 708:717 conditions 708:717 conditions of pharmacological NGLY1 inhibition or NGLY1 KD 708:765 Under conditions of pharmacological NGLY1 inhibition or NGLY1 KD, upregulation of autophagosome formation without impairment of autophagic flux is observed. 34995415 2 27 theme GFP-LC3-positive 450:465 arg1 puncta 467:472 GFP-LC3-positive puncta 450:472 GFP-LC3-positive puncta 450:472 Both pharmacological N-glycanase inhibition by Z-VAD-fmk and siRNA-mediated knockdown (KD) of NGLY1 induce GFP-LC3-positive puncta in HEK 293 cells. 34995415 10 28 theme autophagy 1623:1631 arg1 induction 1610:1618 induction 1610:1618 induction of autophagy 1610:1631 Therefore, experiments with Z-VAD-fmk are complicated by the effects of NGLY1 inhibition, including induction of autophagy, and Q-VD-OPh represents an alternative caspase inhibitor free from this limitation. 34995415 1 29 gly glycoproteins 243:255 arg1 glycoproteins 243:255 glycoproteins 243:255 glycoproteins exported from the endoplasmic reticulum (ER) 243:300 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 1 30 dep peptide 158:164 arg1 NGLY1 180:184 NGLY1 180:184 NGLY1 180:184 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 1 30 dep peptide 158:164 arg1 N-glycanase 167:177 N-glycanase 167:177 peptide: N-glycanase (NGLY1) 158:185 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 10 31 theme free 1691:1694 arg1 inhibitor 1681:1689 an alternative caspase inhibitor 1658:1689 an alternative caspase inhibitor free from this limitation 1658:1715 Therefore, experiments with Z-VAD-fmk are complicated by the effects of NGLY1 inhibition, including induction of autophagy, and Q-VD-OPh represents an alternative caspase inhibitor free from this limitation. 34995415 8 32 theme embryonic 1337:1345 arg1 MEFs 1360:1363 MEFs 1360:1363 MEFs 1360:1363 Upregulation of autophagy represents a cellular adaptation to NGLY1 inhibition or KD, and ATG13-deficient mouse embryonic fibroblasts (MEFs) show reduced viability under these conditions. 34995415 8 32 theme embryonic 1337:1345 arg1 fibroblasts 1347:1357 ATG13-deficient mouse embryonic fibroblasts 1315:1357 ATG13-deficient mouse embryonic fibroblasts (MEFs) 1315:1364 Upregulation of autophagy represents a cellular adaptation to NGLY1 inhibition or KD, and ATG13-deficient mouse embryonic fibroblasts (MEFs) show reduced viability under these conditions. 34995415 0 33 theme Off-target 0:9 arg1 inhibition 11:20 Off-target inhibition 0:20 Off-target inhibition of NGLY1 by the polycaspase inhibitor Z-VAD-fmk 0:68 Off-target inhibition of NGLY1 by the polycaspase inhibitor Z-VAD-fmk induces cellular autophagy. 34995415 1 34 theme endoplasmic 275:285 arg1 ER 298:299 ER 298:299 ER 298:299 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 1 34 theme endoplasmic 275:285 arg1 reticulum 287:295 the endoplasmic reticulum 271:295 the endoplasmic reticulum (ER) 271:300 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 8 35 theme ATG13-deficient 1315:1329 arg1 MEFs 1360:1363 MEFs 1360:1363 MEFs 1360:1363 Upregulation of autophagy represents a cellular adaptation to NGLY1 inhibition or KD, and ATG13-deficient mouse embryonic fibroblasts (MEFs) show reduced viability under these conditions. 34995415 8 35 theme ATG13-deficient 1315:1329 arg1 fibroblasts 1347:1357 ATG13-deficient mouse embryonic fibroblasts 1315:1357 ATG13-deficient mouse embryonic fibroblasts (MEFs) 1315:1364 Upregulation of autophagy represents a cellular adaptation to NGLY1 inhibition or KD, and ATG13-deficient mouse embryonic fibroblasts (MEFs) show reduced viability under these conditions. 34995415 8 36 theme mouse 1331:1335 arg1 MEFs 1360:1363 MEFs 1360:1363 MEFs 1360:1363 Upregulation of autophagy represents a cellular adaptation to NGLY1 inhibition or KD, and ATG13-deficient mouse embryonic fibroblasts (MEFs) show reduced viability under these conditions. 34995415 8 36 theme mouse 1331:1335 arg1 fibroblasts 1347:1357 ATG13-deficient mouse embryonic fibroblasts 1315:1357 ATG13-deficient mouse embryonic fibroblasts (MEFs) 1315:1364 Upregulation of autophagy represents a cellular adaptation to NGLY1 inhibition or KD, and ATG13-deficient mouse embryonic fibroblasts (MEFs) show reduced viability under these conditions. 34995415 0 37 theme NGLY1 25:29 arg1 inhibition 11:20 Off-target inhibition 0:20 Off-target inhibition of NGLY1 by the polycaspase inhibitor Z-VAD-fmk 0:68 Off-target inhibition of NGLY1 by the polycaspase inhibitor Z-VAD-fmk induces cellular autophagy. 34995415 10 38 theme inhibition 1588:1597 arg1 effects 1571:1577 the effects 1567:1577 the effects 1567:1577 Therefore, experiments with Z-VAD-fmk are complicated by the effects of NGLY1 inhibition, including induction of autophagy, and Q-VD-OPh represents an alternative caspase inhibitor free from this limitation. 34995415 10 38 theme inhibition 1588:1597 arg1 induction 1610:1618 induction 1610:1618 induction of autophagy 1610:1631 Therefore, experiments with Z-VAD-fmk are complicated by the effects of NGLY1 inhibition, including induction of autophagy, and Q-VD-OPh represents an alternative caspase inhibitor free from this limitation. 34995415 1 39 link N-linked 221:228 arg1 glycans 230:236 N-linked glycans 221:236 N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) 221:300 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 3 40 theme oxygen 553:558 arg1 species 560:566 reactive oxygen species 544:566 reactive oxygen species (ROS) 544:572 The activation of ER stress markers or induction of reactive oxygen species (ROS) is not observed under either condition. 34995415 3 40 theme oxygen 553:558 arg1 ROS 569:571 ROS 569:571 ROS 569:571 The activation of ER stress markers or induction of reactive oxygen species (ROS) is not observed under either condition. 34995415 5 41 theme flux 841:844 arg1 impairment 816:825 impairment 816:825 impairment of autophagic flux 816:844 Under conditions of pharmacological NGLY1 inhibition or NGLY1 KD, upregulation of autophagosome formation without impairment of autophagic flux is observed. 34995415 10 42 theme NGLY1 1582:1586 arg1 inhibition 1588:1597 NGLY1 inhibition 1582:1597 NGLY1 inhibition 1582:1597 Therefore, experiments with Z-VAD-fmk are complicated by the effects of NGLY1 inhibition, including induction of autophagy, and Q-VD-OPh represents an alternative caspase inhibitor free from this limitation. 34995415 1 43 theme inhibitor 114:122 arg1 Z-VAD-fmk 124:132 The polycaspase inhibitor Z-VAD-fmk 98:132 The polycaspase inhibitor Z-VAD-fmk 98:132 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 1 43 theme inhibitor 114:122 arg1 inhibitor 145:153 an inhibitor 142:153 an inhibitor of peptide: N-glycanase (NGLY1) 142:185 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 11 44 dep ENZYMES 1718:1724 arg1 N-glycanase1 1735:1746 N-glycanase1 1735:1746 N-glycanase1 1735:1746 ENZYMES: Peptide:N-glycanase1, Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase [EC:3.5.1.52]. 34995415 11 44 dep ENZYMES 1718:1724 arg1 N-acetyl-beta-glucosaminyl 1763:1788 N-acetyl-beta-glucosaminyl 1763:1788 N-acetyl-beta-glucosaminyl 1763:1788 ENZYMES: Peptide:N-glycanase1, Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase [EC:3.5.1.52]. 34995415 11 44 dep ENZYMES 1718:1724 arg1 Peptide 1727:1733 Peptide 1727:1733 ENZYMES: Peptide:N-glycanase1, Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase [EC:3.5.1.52]. 1718:1822 ENZYMES: Peptide:N-glycanase1, Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase [EC:3.5.1.52]. 34995415 11 44 dep ENZYMES 1718:1724 arg1 Peptide-N 1749:1757 Peptide-N(4) 1749:1760 Peptide-N(4) 1749:1760 ENZYMES: Peptide:N-glycanase1, Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase [EC:3.5.1.52]. 34995415 5 45 theme autophagic 830:839 arg1 flux 841:844 autophagic flux 830:844 autophagic flux 830:844 Under conditions of pharmacological NGLY1 inhibition or NGLY1 KD, upregulation of autophagosome formation without impairment of autophagic flux is observed. 34995415 1 46 from glycoproteins 243:255 arg1 glycans 230:236 N-linked glycans 221:236 N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) 221:300 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 7 47 theme complex 1204:1210 arg1 disassembly 1212:1222 protein complex disassembly 1196:1222 protein complex disassembly 1196:1222 Gene ontology analysis of proteins enriched in autophagosome IPs shows overrepresentation of factors involved in protein translation, localization and targeting, RNA degradation and protein complex disassembly. 34995415 2 48 theme HEK 477:479 arg1 cells 485:489 HEK 293 cells 477:489 HEK 293 cells 477:489 Both pharmacological N-glycanase inhibition by Z-VAD-fmk and siRNA-mediated knockdown (KD) of NGLY1 induce GFP-LC3-positive puncta in HEK 293 cells. 34995415 6 49 theme protein 997:1003 arg1 content 1005:1011 comparable autophagosomal protein content 971:1011 comparable autophagosomal protein content 971:1011 Enrichment of autophagosomes by immunoprecipitation (IP) and mass spectrometry-based proteomic analysis reveals comparable autophagosomal protein content. 34995415 5 50 theme autophagosome 784:796 arg1 formation 798:806 autophagosome formation 784:806 autophagosome formation 784:806 Under conditions of pharmacological NGLY1 inhibition or NGLY1 KD, upregulation of autophagosome formation without impairment of autophagic flux is observed. 34995415 6 51 theme autophagosomes 873:886 arg1 Enrichment 859:868 Enrichment 859:868 Enrichment of autophagosomes by immunoprecipitation (IP) and mass spectrometry-based proteomic analysis 859:961 Enrichment of autophagosomes by immunoprecipitation (IP) and mass spectrometry-based proteomic analysis reveals comparable autophagosomal protein content. 34995415 2 52 theme NGLY1 437:441 arg1 KD 430:431 KD 430:431 KD 430:431 Both pharmacological N-glycanase inhibition by Z-VAD-fmk and siRNA-mediated knockdown (KD) of NGLY1 induce GFP-LC3-positive puncta in HEK 293 cells. 34995415 2 52 theme NGLY1 437:441 arg1 knockdown 419:427 siRNA-mediated knockdown 404:427 siRNA-mediated knockdown (KD) of NGLY1 404:441 Both pharmacological N-glycanase inhibition by Z-VAD-fmk and siRNA-mediated knockdown (KD) of NGLY1 induce GFP-LC3-positive puncta in HEK 293 cells. 34995415 2 52 theme NGLY1 437:441 arg1 inhibition 376:385 pharmacological N-glycanase inhibition 348:385 pharmacological N-glycanase inhibition by Z-VAD-fmk 348:398 Both pharmacological N-glycanase inhibition by Z-VAD-fmk and siRNA-mediated knockdown (KD) of NGLY1 induce GFP-LC3-positive puncta in HEK 293 cells. 34995415 4 53 theme Ca2+ 624:627 arg1 handling 629:636 Ca2+ handling 624:636 Ca2+ handling 624:636 Moreover, Ca2+ handling is unaffected when observing release from intracellular stores. 34995415 0 54 theme inhibitor 50:58 arg1 Z-VAD-fmk 60:68 the polycaspase inhibitor Z-VAD-fmk 34:68 the polycaspase inhibitor Z-VAD-fmk 34:68 Off-target inhibition of NGLY1 by the polycaspase inhibitor Z-VAD-fmk induces cellular autophagy. 34995415 6 55 theme autophagosomal 982:995 arg1 content 1005:1011 comparable autophagosomal protein content 971:1011 comparable autophagosomal protein content 971:1011 Enrichment of autophagosomes by immunoprecipitation (IP) and mass spectrometry-based proteomic analysis reveals comparable autophagosomal protein content. 34995415 7 56 theme factors 1107:1113 arg1 overrepresentation 1085:1102 overrepresentation 1085:1102 overrepresentation of factors involved in protein translation, localization and targeting, RNA degradation and protein complex disassembly 1085:1222 Gene ontology analysis of proteins enriched in autophagosome IPs shows overrepresentation of factors involved in protein translation, localization and targeting, RNA degradation and protein complex disassembly. 34995415 5 57 theme KD 764:765 arg1 conditions 708:717 conditions 708:717 conditions of pharmacological NGLY1 inhibition or NGLY1 KD 708:765 Under conditions of pharmacological NGLY1 inhibition or NGLY1 KD, upregulation of autophagosome formation without impairment of autophagic flux is observed. 34995415 7 58 theme protein 1127:1133 arg1 translation 1135:1145 protein translation 1127:1145 protein translation 1127:1145 Gene ontology analysis of proteins enriched in autophagosome IPs shows overrepresentation of factors involved in protein translation, localization and targeting, RNA degradation and protein complex disassembly. 34995415 0 59 theme polycaspase 38:48 arg1 Z-VAD-fmk 60:68 the polycaspase inhibitor Z-VAD-fmk 34:68 the polycaspase inhibitor Z-VAD-fmk 34:68 Off-target inhibition of NGLY1 by the polycaspase inhibitor Z-VAD-fmk induces cellular autophagy. 34995415 1 60 theme ER-associated 309:321 arg1 ERAD 336:339 ERAD 336:339 ERAD 336:339 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 1 60 theme ER-associated 309:321 arg1 degradation 323:333 ER-associated degradation 309:333 ER-associated degradation (ERAD) 309:340 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 7 61 theme autophagosome 1061:1073 arg1 IPs 1075:1077 autophagosome IPs 1061:1077 autophagosome IPs 1061:1077 Gene ontology analysis of proteins enriched in autophagosome IPs shows overrepresentation of factors involved in protein translation, localization and targeting, RNA degradation and protein complex disassembly. 34995415 1 62 theme polycaspase 102:112 arg1 Z-VAD-fmk 124:132 The polycaspase inhibitor Z-VAD-fmk 98:132 The polycaspase inhibitor Z-VAD-fmk 98:132 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 1 62 theme polycaspase 102:112 arg1 inhibitor 145:153 an inhibitor 142:153 an inhibitor of peptide: N-glycanase (NGLY1) 142:185 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 8 63 theme autophagy 1241:1249 arg1 Upregulation 1225:1236 Upregulation 1225:1236 Upregulation of autophagy 1225:1249 Upregulation of autophagy represents a cellular adaptation to NGLY1 inhibition or KD, and ATG13-deficient mouse embryonic fibroblasts (MEFs) show reduced viability under these conditions. 34995415 11 64 theme asparagine 1790:1799 arg1 amidase 1801:1807 asparagine amidase [EC:3.5.1.52 1790:1820 asparagine amidase [EC:3.5.1.52 1790:1820 ENZYMES: Peptide:N-glycanase1, Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase [EC:3.5.1.52]. 34995415 7 65 theme proteins 1040:1047 arg1 analysis 1028:1035 Gene ontology analysis 1014:1035 Gene ontology analysis of proteins enriched in autophagosome IPs 1014:1077 Gene ontology analysis of proteins enriched in autophagosome IPs shows overrepresentation of factors involved in protein translation, localization and targeting, RNA degradation and protein complex disassembly. 34995415 3 66 theme markers 520:526 arg1 activation 496:505 The activation 492:505 The activation of ER stress markers 492:526 The activation of ER stress markers or induction of reactive oxygen species (ROS) is not observed under either condition. 34995415 3 66 theme markers 520:526 arg1 induction 531:539 induction 531:539 induction of reactive oxygen species (ROS) 531:572 The activation of ER stress markers or induction of reactive oxygen species (ROS) is not observed under either condition. 34995415 1 67 theme N-linked 221:228 arg1 glycans 230:236 N-linked glycans 221:236 N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) 221:300 The polycaspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide: N-glycanase (NGLY1), an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). 34995415 5 68 theme NGLY1 758:762 arg1 KD 764:765 NGLY1 KD 758:765 NGLY1 KD 758:765 Under conditions of pharmacological NGLY1 inhibition or NGLY1 KD, upregulation of autophagosome formation without impairment of autophagic flux is observed. 34995415 3 69 theme stress 513:518 arg1 markers 520:526 ER stress markers 510:526 ER stress markers 510:526 The activation of ER stress markers or induction of reactive oxygen species (ROS) is not observed under either condition. 34995415 11 70 dep N-acetyl-beta-glucosaminyl 1763:1788 arg1 amidase 1801:1807 asparagine amidase [EC:3.5.1.52 1790:1820 asparagine amidase [EC:3.5.1.52 1790:1820 ENZYMES: Peptide:N-glycanase1, Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase [EC:3.5.1.52]. 34995415 5 71 theme formation 798:806 arg1 upregulation 768:779 upregulation 768:779 upregulation of autophagosome formation without impairment of autophagic flux 768:844 Under conditions of pharmacological NGLY1 inhibition or NGLY1 KD, upregulation of autophagosome formation without impairment of autophagic flux is observed. 34995415 2 72 theme N-glycanase 364:374 arg1 inhibition 376:385 pharmacological N-glycanase inhibition 348:385 pharmacological N-glycanase inhibition by Z-VAD-fmk 348:398 Both pharmacological N-glycanase inhibition by Z-VAD-fmk and siRNA-mediated knockdown (KD) of NGLY1 induce GFP-LC3-positive puncta in HEK 293 cells. 34995415 4 73 from stores 694:699 arg1 release 667:673 release 667:673 release from intracellular stores 667:699 Moreover, Ca2+ handling is unaffected when observing release from intracellular stores. 34995415 10 74 theme alternative 1661:1671 arg1 inhibitor 1681:1689 an alternative caspase inhibitor 1658:1689 an alternative caspase inhibitor free from this limitation 1658:1715 Therefore, experiments with Z-VAD-fmk are complicated by the effects of NGLY1 inhibition, including induction of autophagy, and Q-VD-OPh represents an alternative caspase inhibitor free from this limitation. 37172586 5 0 theme MGAT5 813:817 arg1 loss 805:808 loss 805:808 loss of MGAT5 805:817 In the brain cerebral cortex, loss of MGAT5 caused accelerated neuronal differentiation. 37172586 6 1 theme cortical 964:971 arg1 layers 980:985 cortical neuron layers 964:985 cortical neuron layers in Mgat5 null mice 964:1004 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 3 2 theme N-acetylglucosaminyltransferase 548:578 arg1 enzyme 489:494 the enzyme 485:494 the enzyme responsible for generating β1,6-branched N-glycans 485:545 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 3 2 theme N-acetylglucosaminyltransferase 548:578 arg1 V 580:580 N-acetylglucosaminyltransferase V 548:580 N-acetylglucosaminyltransferase V (MGAT5) 548:588 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 3 2 theme N-acetylglucosaminyltransferase 548:578 arg1 MGAT5 583:587 MGAT5 583:587 MGAT5 583:587 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 0 3 theme MGAT5-mediated 72:85 arg1 N-glycosylation 87:101 MGAT5-mediated N-glycosylation 72:101 MGAT5-mediated N-glycosylation 72:101 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. 37172586 7 4 theme Glycosylation 1007:1019 arg1 MGAT5 1028:1032 Glycosylation enzyme MGAT5 1007:1032 Glycosylation enzyme MGAT5 1007:1032 Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development. 37172586 2 5 theme cell 382:385 arg1 differentiation 387:401 cell differentiation 382:401 cell differentiation 382:401 Membrane proteins are regulated by N-linked glycosylation, making it possible that glycosylation plays a critical role in cell differentiation. 37172586 5 6 theme brain 782:786 arg1 cortex 797:802 the brain cerebral cortex 778:802 the brain cerebral cortex 778:802 In the brain cerebral cortex, loss of MGAT5 caused accelerated neuronal differentiation. 37172586 7 7 theme enzyme 1021:1026 arg1 MGAT5 1028:1032 Glycosylation enzyme MGAT5 1007:1032 Glycosylation enzyme MGAT5 1007:1032 Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development. 37172586 2 8 link N-linked 295:302 arg1 glycosylation 304:316 N-linked glycosylation 295:316 N-linked glycosylation 295:316 Membrane proteins are regulated by N-linked glycosylation, making it possible that glycosylation plays a critical role in cell differentiation. 37172586 5 9 theme cerebral 788:795 arg1 cortex 797:802 the brain cerebral cortex 778:802 the brain cerebral cortex 778:802 In the brain cerebral cortex, loss of MGAT5 caused accelerated neuronal differentiation. 37172586 3 10 gly N-glycosylation 437:451 arg1 NSPCs 456:460 NSPCs 456:460 NSPCs 456:460 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 6 11 theme neuronal 870:877 arg1 differentiation 879:893 Rapid neuronal differentiation 864:893 Rapid neuronal differentiation 864:893 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 4 12 theme wild-type 755:763 arg1 controls 765:772 wild-type controls 755:772 wild-type controls 755:772 Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. 37172586 6 13 theme Rapid 864:868 arg1 differentiation 879:893 Rapid neuronal differentiation 864:893 Rapid neuronal differentiation 864:893 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 5 14 theme accelerated 826:836 arg1 differentiation 847:861 accelerated neuronal differentiation 826:861 accelerated neuronal differentiation 826:861 In the brain cerebral cortex, loss of MGAT5 caused accelerated neuronal differentiation. 37172586 7 15 theme critical 1042:1049 arg1 role 1079:1082 a critical and previously unrecognized role 1040:1082 a critical and previously unrecognized role 1040:1082 Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development. 37172586 4 16 theme more 707:710 arg1 neurons 712:718 more neurons 707:718 more neurons 707:718 Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. 37172586 6 17 from layers 980:985 arg1 mice 1001:1004 Mgat5 null mice 990:1004 Mgat5 null mice 990:1004 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 4 18 theme fewer 724:728 arg1 astrocytes 730:739 fewer astrocytes 724:739 fewer astrocytes 724:739 Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. 37172586 1 19 theme Undifferentiated 104:119 arg1 NSPCs 155:159 NSPCs 155:159 NSPCs 155:159 Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. 37172586 1 19 theme Undifferentiated 104:119 arg1 stem 128:131 Undifferentiated neural stem and progenitor cells 104:152 stem 128:131 Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. 37172586 1 20 theme plasma 204:209 arg1 proteins 220:227 plasma membrane proteins 204:227 plasma membrane proteins 204:227 Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. 37172586 0 21 theme stem 21:24 arg1 differentiation 31:45 neural stem cell differentiation 14:45 neural stem cell differentiation 14:45 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. 37172586 6 22 from depletion 902:910 arg1 niche 933:937 the NSPC niche 924:937 the NSPC niche 924:937 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 1 23 theme neural 121:126 arg1 NSPCs 155:159 NSPCs 155:159 NSPCs 155:159 Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. 37172586 1 23 theme neural 121:126 arg1 stem 128:131 Undifferentiated neural stem and progenitor cells 104:152 stem 128:131 Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. 37172586 1 24 theme membrane 211:218 arg1 proteins 220:227 plasma membrane proteins 204:227 plasma membrane proteins 204:227 Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. 37172586 3 25 theme NSPC 618:621 arg1 in vitro 639:646 NSPC differentiation in vitro 618:646 NSPC differentiation in vitro 618:646 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 1 26 theme extracellular 172:184 arg1 signals 186:192 extracellular signals 172:192 extracellular signals that bind plasma membrane proteins and influence differentiation 172:257 Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. 37172586 0 27 theme differentiation 31:45 arg1 Regulation 0:9 Regulation 0:9 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. 0:102 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. 37172586 7 28 theme early 1112:1116 arg1 development 1124:1134 early brain development 1112:1134 early brain development 1112:1134 Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development. 37172586 6 29 theme NSPC 928:931 arg1 niche 933:937 the NSPC niche 924:937 the NSPC niche 924:937 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 4 30 from NSPCs 683:687 arg1 culture 692:698 culture 692:698 culture 692:698 Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. 37172586 0 31 theme cell 26:29 arg1 differentiation 31:45 neural stem cell differentiation 14:45 neural stem cell differentiation 14:45 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. 37172586 6 32 theme null 996:999 arg1 mice 1001:1004 Mgat5 null mice 990:1004 Mgat5 null mice 990:1004 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 5 33 theme neuronal 838:845 arg1 differentiation 847:861 accelerated neuronal differentiation 826:861 accelerated neuronal differentiation 826:861 In the brain cerebral cortex, loss of MGAT5 caused accelerated neuronal differentiation. 37172586 2 34 theme Membrane 260:267 arg1 proteins 269:276 Membrane proteins 260:276 Membrane proteins 260:276 Membrane proteins are regulated by N-linked glycosylation, making it possible that glycosylation plays a critical role in cell differentiation. 37172586 7 35 theme unrecognized 1066:1077 arg1 role 1079:1082 a critical and previously unrecognized role 1040:1082 a critical and previously unrecognized role 1040:1082 Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development. 37172586 3 36 theme enzyme 489:494 arg1 loss 477:480 loss 477:480 loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), 477:589 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 0 37 theme brain 51:55 arg1 development 57:67 brain development 51:67 brain development 51:67 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. 37172586 6 38 theme Mgat5 990:994 arg1 mice 1001:1004 Mgat5 null mice 990:1004 Mgat5 null mice 990:1004 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 6 39 from shift 955:959 arg1 layers 980:985 cortical neuron layers 964:985 cortical neuron layers in Mgat5 null mice 964:1004 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 3 40 theme differentiation 623:637 arg1 in vitro 639:646 NSPC differentiation in vitro 618:646 NSPC differentiation in vitro 618:646 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 7 41 theme brain 1118:1122 arg1 development 1124:1134 early brain development 1112:1134 early brain development 1112:1134 Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development. 37172586 6 42 theme neuron 973:978 arg1 layers 980:985 cortical neuron layers 964:985 cortical neuron layers in Mgat5 null mice 964:1004 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 6 43 theme cells 915:919 arg1 depletion 902:910 depletion 902:910 depletion of cells in the NSPC niche 902:937 Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. 37172586 1 44 theme progenitor 137:146 arg1 cells 148:152 Undifferentiated neural stem and progenitor cells 104:152 cells 148:152 Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. 37172586 2 45 theme N-linked 295:302 arg1 glycosylation 304:316 N-linked glycosylation 295:316 N-linked glycosylation 295:316 Membrane proteins are regulated by N-linked glycosylation, making it possible that glycosylation plays a critical role in cell differentiation. 37172586 2 46 theme critical 365:372 arg1 role 374:377 a critical role 363:377 a critical role 363:377 Membrane proteins are regulated by N-linked glycosylation, making it possible that glycosylation plays a critical role in cell differentiation. 37172586 3 47 theme specific 598:605 arg1 changes 607:613 specific changes 598:613 specific changes in NSPC differentiation in vitro and in vivo 598:658 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 4 48 theme Mgat5 661:665 arg1 NSPCs 683:687 Mgat5 homozygous null NSPCs 661:687 Mgat5 homozygous null NSPCs in culture 661:698 Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. 37172586 7 49 theme cell 1087:1090 arg1 differentiation 1092:1106 cell differentiation 1087:1106 cell differentiation 1087:1106 Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development. 37172586 3 50 theme β1,6-branched 523:535 arg1 N-glycans 537:545 β1,6-branched N-glycans 523:545 β1,6-branched N-glycans 523:545 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 3 51 theme responsible 496:506 arg1 enzyme 489:494 the enzyme 485:494 the enzyme responsible for generating β1,6-branched N-glycans 485:545 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 3 51 theme responsible 496:506 arg1 V 580:580 N-acetylglucosaminyltransferase V 548:580 N-acetylglucosaminyltransferase V (MGAT5) 548:588 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 3 52 from changes 607:613 arg1 in vivo 652:658 in vivo 652:658 in vivo 652:658 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 3 52 from changes 607:613 arg1 in vitro 639:646 NSPC differentiation in vitro 618:646 NSPC differentiation in vitro 618:646 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 4 53 theme null 678:681 arg1 NSPCs 683:687 Mgat5 homozygous null NSPCs 661:687 Mgat5 homozygous null NSPCs in culture 661:698 Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. 37172586 0 54 theme development 57:67 arg1 Regulation 0:9 Regulation 0:9 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. 0:102 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. 37172586 3 55 from N-glycosylation 437:451 arg1 NSPCs 456:460 NSPCs 456:460 NSPCs 456:460 We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. 37172586 0 56 theme neural 14:19 arg1 differentiation 31:45 neural stem cell differentiation 14:45 neural stem cell differentiation 14:45 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. 37172586 4 57 theme homozygous 667:676 arg1 NSPCs 683:687 Mgat5 homozygous null NSPCs 661:687 Mgat5 homozygous null NSPCs in culture 661:698 Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. 36948700 5 0 theme spike 843:847 arg1 proteins 849:856 spike proteins 843:856 spike proteins 843:856 Since the immunogenicity of spike proteins may be impacted by their glycosylation patterns, site-specific analysis of N-glycoforms provides critical information for vaccine design. 36948700 6 1 theme soluble 1026:1032 arg1 trimer 1042:1047 recombinantly expressed soluble HIV Env trimer 1002:1047 recombinantly expressed soluble HIV Env trimer 1002:1047 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 1 2 from N-glycans 325:333 arg1 glycoproteins 338:350 glycoproteins 338:350 glycoproteins 338:350 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 1 3 theme site-specific 172:184 arg1 analysis 198:205 site-specific N-glycoform analysis 172:205 site-specific N-glycoform analysis 172:205 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 5 4 theme proteins 849:856 arg1 immunogenicity 825:838 the immunogenicity 821:838 the immunogenicity of spike proteins 821:856 Since the immunogenicity of spike proteins may be impacted by their glycosylation patterns, site-specific analysis of N-glycoforms provides critical information for vaccine design. 36948700 6 5 theme expressed 1016:1024 arg1 trimer 1042:1047 recombinantly expressed soluble HIV Env trimer 1002:1047 recombinantly expressed soluble HIV Env trimer 1002:1047 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 7 6 theme rapid 1224:1228 arg1 approach 1253:1260 an ultrasensitive, simple, rapid, robust, and efficient approach 1197:1260 approach 1253:1260 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 7 6 theme rapid 1224:1228 arg1 DeGlyPHER 1184:1192 DeGlyPHER 1184:1192 DeGlyPHER 1184:1192 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 1 7 theme N-glycoform 186:196 arg1 analysis 198:205 site-specific N-glycoform analysis 172:205 site-specific N-glycoform analysis 172:205 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 7 8 theme protein 1292:1298 arg1 N-glycoforms 1300:1311 protein N-glycoforms 1292:1311 protein N-glycoforms 1292:1311 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 1 9 from diversity 312:320 arg1 glycoproteins 338:350 glycoproteins 338:350 glycoproteins 338:350 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 7 10 gly N-glycoforms 1300:1311 arg1 protein 1292:1298 protein N-glycoforms 1292:1311 protein N-glycoforms 1292:1311 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 7 11 theme N-glycoforms 1300:1311 arg1 analysis 1280:1287 site-specific analysis 1266:1287 site-specific analysis of protein N-glycoforms 1266:1311 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 7 12 theme simple 1216:1221 arg1 approach 1253:1260 an ultrasensitive, simple, rapid, robust, and efficient approach 1197:1260 approach 1253:1260 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 7 12 theme simple 1216:1221 arg1 DeGlyPHER 1184:1192 DeGlyPHER 1184:1192 DeGlyPHER 1184:1192 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 4 13 gly glycosylated 671:682 arg1 targets 778:784 prime targets 772:784 prime targets for glycoproteomic analysis 772:812 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 4 13 gly glycosylated 671:682 arg1 proteins 690:697 Heavily glycosylated spike proteins 663:697 Heavily glycosylated spike proteins 663:697 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 6 14 theme reported 1106:1113 arg1 strategy 1142:1149 our previously reported sequential deglycosylation strategy 1091:1149 our previously reported sequential deglycosylation strategy 1091:1149 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 6 15 theme strategy 1142:1149 arg1 DeGlyPHER 1062:1070 DeGlyPHER 1062:1070 DeGlyPHER 1062:1070 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 6 15 theme strategy 1142:1149 arg1 modification 1075:1086 a modification 1073:1086 a modification of our previously reported sequential deglycosylation strategy 1073:1149 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 1 16 gly glycoproteins 338:350 arg1 glycoproteins 338:350 glycoproteins 338:350 glycoproteins 338:350 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 0 17 from analysis 42:49 arg1 proteins 74:81 proteins 74:81 proteins 74:81 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 36948700 7 18 theme ultrasensitive 1200:1213 arg1 approach 1253:1260 an ultrasensitive, simple, rapid, robust, and efficient approach 1197:1260 approach 1253:1260 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 7 18 theme ultrasensitive 1200:1213 arg1 DeGlyPHER 1184:1192 DeGlyPHER 1184:1192 DeGlyPHER 1184:1192 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 0 19 link N-linked 54:61 arg1 glycans 63:69 N-linked glycans 54:69 N-linked glycans 54:69 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 36948700 1 20 used used 163:166 arg2 approaches 135:144 Traditional mass spectrometry-based glycoproteomic approaches 84:144 Traditional mass spectrometry-based glycoproteomic approaches 84:144 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 5 21 theme critical 955:962 arg1 information 964:974 critical information 955:974 critical information for vaccine design 955:993 Since the immunogenicity of spike proteins may be impacted by their glycosylation patterns, site-specific analysis of N-glycoforms provides critical information for vaccine design. 36948700 4 22 theme enveloped 702:710 arg1 viruses 712:718 enveloped viruses 702:718 enveloped viruses 702:718 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 7 23 theme limited 1348:1354 arg1 quantities 1356:1365 limited quantities 1348:1365 limited quantities of glycoproteins 1348:1382 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 1 24 theme Traditional 84:94 arg1 approaches 135:144 Traditional mass spectrometry-based glycoproteomic approaches 84:144 Traditional mass spectrometry-based glycoproteomic approaches 84:144 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 6 25 theme " 1173:1173 arg1 process 1175:1181 a "single-pot" process 1160:1181 a "single-pot" process 1160:1181 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 5 26 theme glycosylation 883:895 arg1 patterns 897:904 their glycosylation patterns 877:904 their glycosylation patterns 877:904 Since the immunogenicity of spike proteins may be impacted by their glycosylation patterns, site-specific analysis of N-glycoforms provides critical information for vaccine design. 36948700 1 27 theme mass 96:99 arg1 approaches 135:144 Traditional mass spectrometry-based glycoproteomic approaches 84:144 Traditional mass spectrometry-based glycoproteomic approaches 84:144 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 3 28 from heterogeneity 628:640 arg1 samples 654:660 clinical samples 645:660 clinical samples 645:660 These limitations have prevented glycoproteomics from being adapted to high-throughput platforms, and the sensitivity of the analysis is currently inadequate for elucidating N-glycan heterogeneity in clinical samples. 36948700 2 29 theme complicated 388:398 arg1 workflow 400:407 a complicated workflow 386:407 a complicated workflow 386:407 These methods also often include a complicated workflow and very challenging data analysis. 36948700 0 30 theme sensitive 18:26 arg1 analysis 42:49 Highly sensitive site-specific analysis 11:49 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 0:82 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 36948700 1 31 theme spectrometry-based 101:118 arg1 approaches 135:144 Traditional mass spectrometry-based glycoproteomic approaches 84:144 Traditional mass spectrometry-based glycoproteomic approaches 84:144 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 1 32 theme large 214:218 arg1 amount 220:225 a large amount 212:225 a large amount of starting material 212:246 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 1 32 theme large 214:218 arg1 material 239:246 starting material 230:246 starting material 230:246 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 3 33 theme N-glycan 619:626 arg1 heterogeneity 628:640 N-glycan heterogeneity 619:640 N-glycan heterogeneity in clinical samples 619:660 These limitations have prevented glycoproteomics from being adapted to high-throughput platforms, and the sensitivity of the analysis is currently inadequate for elucidating N-glycan heterogeneity in clinical samples. 36948700 1 34 theme glycoproteomic 120:133 arg1 approaches 135:144 Traditional mass spectrometry-based glycoproteomic approaches 84:144 Traditional mass spectrometry-based glycoproteomic approaches 84:144 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 1 35 theme vast 307:310 arg1 diversity 312:320 the vast diversity 303:320 the vast diversity of N-glycans on glycoproteins 303:350 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 4 36 theme viruses 712:718 arg1 targets 778:784 prime targets 772:784 prime targets for glycoproteomic analysis 772:812 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 4 36 theme viruses 712:718 arg1 proteins 690:697 Heavily glycosylated spike proteins 663:697 Heavily glycosylated spike proteins 663:697 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 3 37 theme clinical 645:652 arg1 samples 654:660 clinical samples 645:660 clinical samples 645:660 These limitations have prevented glycoproteomics from being adapted to high-throughput platforms, and the sensitivity of the analysis is currently inadequate for elucidating N-glycan heterogeneity in clinical samples. 36948700 6 38 theme single-pot 1163:1172 arg1 process 1175:1181 a "single-pot" process 1160:1181 a "single-pot" process 1160:1181 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 2 39 theme data 430:433 arg1 analysis 435:442 very challenging data analysis 413:442 very challenging data analysis 413:442 These methods also often include a complicated workflow and very challenging data analysis. 36948700 0 40 theme site-specific 28:40 arg1 analysis 42:49 Highly sensitive site-specific analysis 11:49 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 0:82 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 36948700 1 41 theme diversity 312:320 arg1 representative 285:298 representative 285:298 representative 285:298 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 6 42 theme sequential 1115:1124 arg1 strategy 1142:1149 our previously reported sequential deglycosylation strategy 1091:1149 our previously reported sequential deglycosylation strategy 1091:1149 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 5 43 theme N-glycoforms 933:944 arg1 analysis 921:928 site-specific analysis 907:928 site-specific analysis of N-glycoforms 907:944 Since the immunogenicity of spike proteins may be impacted by their glycosylation patterns, site-specific analysis of N-glycoforms provides critical information for vaccine design. 36948700 1 44 theme starting 230:237 arg1 material 239:246 starting material 230:246 starting material 230:246 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 1 45 from glycoproteins 338:350 arg1 diversity 312:320 the vast diversity 303:320 the vast diversity of N-glycans on glycoproteins 303:350 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 0 46 theme glycans 63:69 arg1 analysis 42:49 Highly sensitive site-specific analysis 11:49 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 0:82 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 36948700 7 47 theme glycoproteins 1370:1382 arg1 quantities 1356:1365 limited quantities 1348:1365 limited quantities of glycoproteins 1348:1382 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 7 48 theme robust 1231:1236 arg1 approach 1253:1260 an ultrasensitive, simple, rapid, robust, and efficient approach 1197:1260 approach 1253:1260 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 7 48 theme robust 1231:1236 arg1 DeGlyPHER 1184:1192 DeGlyPHER 1184:1192 DeGlyPHER 1184:1192 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 1 49 theme N-glycans 325:333 arg1 diversity 312:320 the vast diversity 303:320 the vast diversity of N-glycans on glycoproteins 303:350 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 7 50 gly glycoproteins 1370:1382 arg1 glycoproteins 1370:1382 glycoproteins 1370:1382 glycoproteins 1370:1382 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 4 51 theme prime 772:776 arg1 targets 778:784 prime targets 772:784 prime targets for glycoproteomic analysis 772:812 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 4 51 theme prime 772:776 arg1 proteins 690:697 Heavily glycosylated spike proteins 663:697 Heavily glycosylated spike proteins 663:697 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 6 52 theme Env 1038:1040 arg1 trimer 1042:1047 recombinantly expressed soluble HIV Env trimer 1002:1047 recombinantly expressed soluble HIV Env trimer 1002:1047 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 4 53 theme glycoproteomic 790:803 arg1 analysis 805:812 glycoproteomic analysis 790:812 glycoproteomic analysis 790:812 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 1 54 theme material 239:246 arg1 amount 220:225 a large amount 212:225 a large amount of starting material 212:246 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 1 54 theme material 239:246 arg1 material 239:246 starting material 230:246 starting material 230:246 Traditional mass spectrometry-based glycoproteomic approaches have been widely used for site-specific N-glycoform analysis, but a large amount of starting material is needed to obtain sampling that is representative of the vast diversity of N-glycans on glycoproteins. 36948700 3 55 theme analysis 570:577 arg1 sensitivity 551:561 the sensitivity 547:561 the sensitivity of the analysis 547:577 These limitations have prevented glycoproteomics from being adapted to high-throughput platforms, and the sensitivity of the analysis is currently inadequate for elucidating N-glycan heterogeneity in clinical samples. 36948700 3 55 theme analysis 570:577 arg1 inadequate 592:601 inadequate 592:601 inadequate 592:601 These limitations have prevented glycoproteomics from being adapted to high-throughput platforms, and the sensitivity of the analysis is currently inadequate for elucidating N-glycan heterogeneity in clinical samples. 36948700 3 56 theme high-throughput 516:530 arg1 platforms 532:540 high-throughput platforms 516:540 high-throughput platforms 516:540 These limitations have prevented glycoproteomics from being adapted to high-throughput platforms, and the sensitivity of the analysis is currently inadequate for elucidating N-glycan heterogeneity in clinical samples. 36948700 7 57 theme efficient 1243:1251 arg1 approach 1253:1260 an ultrasensitive, simple, rapid, robust, and efficient approach 1197:1260 approach 1253:1260 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 7 57 theme efficient 1243:1251 arg1 DeGlyPHER 1184:1192 DeGlyPHER 1184:1192 DeGlyPHER 1184:1192 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 6 58 theme deglycosylation 1126:1140 arg1 strategy 1142:1149 our previously reported sequential deglycosylation strategy 1091:1149 our previously reported sequential deglycosylation strategy 1091:1149 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 2 59 theme challenging 418:428 arg1 analysis 435:442 very challenging data analysis 413:442 very challenging data analysis 413:442 These methods also often include a complicated workflow and very challenging data analysis. 36948700 5 60 theme site-specific 907:919 arg1 analysis 921:928 site-specific analysis 907:928 site-specific analysis of N-glycoforms 907:944 Since the immunogenicity of spike proteins may be impacted by their glycosylation patterns, site-specific analysis of N-glycoforms provides critical information for vaccine design. 36948700 5 61 theme vaccine 980:986 arg1 design 988:993 vaccine design 980:993 vaccine design 980:993 Since the immunogenicity of spike proteins may be impacted by their glycosylation patterns, site-specific analysis of N-glycoforms provides critical information for vaccine design. 36948700 4 62 theme spike 684:688 arg1 targets 778:784 prime targets 772:784 prime targets for glycoproteomic analysis 772:812 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 4 62 theme spike 684:688 arg1 proteins 690:697 Heavily glycosylated spike proteins 663:697 Heavily glycosylated spike proteins 663:697 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 0 63 theme N-linked 54:61 arg1 glycans 63:69 N-linked glycans 54:69 N-linked glycans 54:69 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 36948700 6 64 theme HIV 1034:1036 arg1 trimer 1042:1047 recombinantly expressed soluble HIV Env trimer 1002:1047 recombinantly expressed soluble HIV Env trimer 1002:1047 Using recombinantly expressed soluble HIV Env trimer, we describe DeGlyPHER, a modification of our previously reported sequential deglycosylation strategy to yield a "single-pot" process. 36948700 0 65 dep DeGlyPHER 0:8 arg1 analysis 42:49 Highly sensitive site-specific analysis 11:49 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 0:82 DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins. 36948700 7 66 theme quantities 1356:1365 arg1 analysis 1336:1343 analysis 1336:1343 analysis of limited quantities of glycoproteins 1336:1382 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 4 67 theme potential 748:756 arg1 vaccines 758:765 potential vaccines 748:765 potential vaccines 748:765 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 7 68 theme site-specific 1266:1278 arg1 analysis 1280:1287 site-specific analysis 1266:1287 site-specific analysis of protein N-glycoforms 1266:1311 DeGlyPHER is an ultrasensitive, simple, rapid, robust, and efficient approach for site-specific analysis of protein N-glycoforms, that we developed for analysis of limited quantities of glycoproteins. 36948700 4 69 theme glycosylated 671:682 arg1 targets 778:784 prime targets 772:784 prime targets for glycoproteomic analysis 772:812 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36948700 4 69 theme glycosylated 671:682 arg1 proteins 690:697 Heavily glycosylated spike proteins 663:697 Heavily glycosylated spike proteins 663:697 Heavily glycosylated spike proteins of enveloped viruses, recombinantly expressed as potential vaccines, are prime targets for glycoproteomic analysis. 36810563 2 0 theme critical 358:365 arg1 phase 367:371 the most critical phase 349:371 the most critical phase of infection 349:384 Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. 36810563 2 0 theme critical 358:365 arg1 attachment 335:344 zoospore root attachment 321:344 zoospore root attachment 321:344 Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. 36810563 9 1 theme resistant 1512:1520 arg1 cultivar 1522:1529 the resistant cultivar 1508:1529 the resistant cultivar in both the TS and whole-root datasets 1508:1568 A further major latex protein was reduced in the resistant cultivar in both the TS and whole-root datasets. 36810563 4 2 theme removal 638:644 arg1 effects 617:623 the effects 613:623 the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment 613:738 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 7 3 theme proteins 1209:1216 arg1 different 1278:1286 different 1278:1286 different 1278:1286 Comparison with whole-root proteomic analysis of the same cultivars identified 226 proteins specific to the TS dataset, of which 188 were significantly different. 36810563 3 4 theme zoospore 574:581 arg1 attachment 583:592 zoospore attachment 574:592 zoospore attachment 574:592 This study investigated the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment. 36810563 4 5 theme subterranea 717:727 arg1 attachment 729:738 S. subterranea attachment 714:738 S. subterranea attachment 714:738 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 7 6 theme same 1179:1182 arg1 cultivars 1184:1192 the same cultivars 1175:1192 the same cultivars 1175:1192 Comparison with whole-root proteomic analysis of the same cultivars identified 226 proteins specific to the TS dataset, of which 188 were significantly different. 36810563 2 7 theme zoospore 321:328 arg1 phase 367:371 the most critical phase 349:371 the most critical phase of infection 349:384 Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. 36810563 2 7 theme zoospore 321:328 arg1 attachment 335:344 zoospore root attachment 321:344 zoospore root attachment 321:344 Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. 36810563 6 8 theme lignin 1053:1058 arg1 biosynthesis 1060:1071 lignin biosynthesis 1053:1071 lignin biosynthesis 1053:1071 These were enriched in root-surface-derived peptides but also included intracellular proteins, e.g., proteins associated with glutathione metabolism and lignin biosynthesis, which were more abundant in the resistant cultivar. 36810563 4 9 theme N-linked 674:681 arg1 glycans 683:689 N-linked glycans 674:689 N-linked glycans 674:689 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 5 10 theme peptides 764:771 arg1 analysis 752:759 Subsequent analysis 741:759 Subsequent analysis of peptides released by trypsin shaving (TS) of root segments 741:821 Subsequent analysis of peptides released by trypsin shaving (TS) of root segments identified 262 proteins that were differentially abundant between cultivars. 36810563 6 11 dep proteins 1001:1008 arg1 e.g. 995:998 e.g. 995:998 e.g. 995:998 These were enriched in root-surface-derived peptides but also included intracellular proteins, e.g., proteins associated with glutathione metabolism and lignin biosynthesis, which were more abundant in the resistant cultivar. 36810563 7 12 theme proteomic 1153:1161 arg1 analysis 1163:1170 whole-root proteomic analysis 1142:1170 whole-root proteomic analysis of the same cultivars 1142:1192 Comparison with whole-root proteomic analysis of the same cultivars identified 226 proteins specific to the TS dataset, of which 188 were significantly different. 36810563 8 13 theme pathogen-defence-related 1306:1329 arg1 abundant 1427:1434 abundant 1427:1434 abundant 1427:1434 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 8 13 theme pathogen-defence-related 1306:1329 arg1 protein 1341:1347 the pathogen-defence-related cell-wall protein 1302:1347 the pathogen-defence-related cell-wall protein 1302:1347 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 8 14 theme latex 1388:1392 arg1 proteins 1394:1401 two major latex proteins 1378:1401 two major latex proteins 1378:1401 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 10 15 theme glucan 1703:1708 arg1 endo-1,3-beta-glucosidase 1710:1734 the protein glucan endo-1,3-beta-glucosidase 1691:1734 the protein glucan endo-1,3-beta-glucosidase 1691:1734 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 10 16 from contrast 1574:1581 arg1 abundant 1635:1642 abundant 1635:1642 abundant 1635:1642 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 4 17 link N-linked 674:681 arg1 glycans 683:689 N-linked glycans 674:689 N-linked glycans 674:689 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 1 18 theme potato 154:159 arg1 crops 161:165 potato crops 154:165 potato crops 154:165 For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. 36810563 11 19 theme potato 1902:1907 arg1 roots 1909:1913 potato roots 1902:1913 potato roots 1902:1913 These results imply a particular role for major latex proteins and glucan endo-1,3-beta-glucosidase in regulating zoospore binding to potato roots and susceptibility to S. subterranea. 36810563 0 20 theme Potato 83:88 arg1 Cultivars 90:98 Potato Cultivars 83:98 Potato Cultivars Resistant or Susceptible to Powdery Scab Disease 83:147 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 8 21 theme resistant 1443:1451 arg1 cultivar 1453:1460 the resistant cultivar 1439:1460 the resistant cultivar 1439:1460 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 0 22 theme Resistant 100:108 arg1 Cultivars 90:98 Potato Cultivars 83:98 Potato Cultivars Resistant or Susceptible to Powdery Scab Disease 83:147 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 4 23 from effects 617:623 arg1 attachment 729:738 S. subterranea attachment 714:738 S. subterranea attachment 714:738 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 0 24 theme Enzymatic 0:8 arg1 Investigation 10:22 Enzymatic Investigation 0:22 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 0:148 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 1 25 theme plasmodiophorid 270:284 arg1 subterranea 298:308 the plasmodiophorid Spongospora subterranea 266:308 the plasmodiophorid Spongospora subterranea 266:308 For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. 36810563 10 26 from abundant 1635:1642 arg1 contrast 1574:1581 contrast 1574:1581 contrast 1574:1581 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 10 26 from abundant 1635:1642 arg1 TS-specific 1671:1681 TS-specific 1671:1681 TS-specific 1671:1681 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 10 26 from abundant 1635:1642 arg1 cultivar 1661:1668 the resistant cultivar 1647:1668 the resistant cultivar (TS-specific) 1647:1682 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 10 27 theme glutathione 1590:1600 arg1 proteins 1616:1623 three glutathione S-transferase proteins 1584:1623 three glutathione S-transferase proteins 1584:1623 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 11 28 theme major 1810:1814 arg1 proteins 1822:1829 major latex proteins 1810:1829 major latex proteins 1810:1829 These results imply a particular role for major latex proteins and glucan endo-1,3-beta-glucosidase in regulating zoospore binding to potato roots and susceptibility to S. subterranea. 36810563 0 29 theme subterranea 39:49 arg1 Attachment 60:69 Spongospora subterranea Zoospore Attachment 27:69 Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease 27:147 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 3 30 theme polysaccharides 507:521 arg1 role 476:479 the potential role 462:479 the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment 462:592 This study investigated the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment. 36810563 0 31 theme Attachment 60:69 arg1 Investigation 10:22 Enzymatic Investigation 0:22 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 0:148 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 9 32 theme major 1473:1477 arg1 protein 1485:1491 A further major latex protein 1463:1491 A further major latex protein 1463:1491 A further major latex protein was reduced in the resistant cultivar in both the TS and whole-root datasets. 36810563 11 33 theme glucan 1835:1840 arg1 endo-1,3-beta-glucosidase 1842:1866 glucan endo-1,3-beta-glucosidase 1835:1866 glucan endo-1,3-beta-glucosidase 1835:1866 These results imply a particular role for major latex proteins and glucan endo-1,3-beta-glucosidase in regulating zoospore binding to potato roots and susceptibility to S. subterranea. 36810563 3 34 theme root-surface 484:495 arg1 polysaccharides 507:521 root-surface cell-wall polysaccharides 484:521 root-surface cell-wall polysaccharides 484:521 This study investigated the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment. 36810563 8 35 from cultivar 1453:1460 arg1 abundant 1427:1434 abundant 1427:1434 abundant 1427:1434 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 8 35 from cultivar 1453:1460 arg1 protein 1341:1347 the pathogen-defence-related cell-wall protein 1302:1347 the pathogen-defence-related cell-wall protein 1302:1347 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 1 36 theme sustainable 220:230 arg1 tool 232:235 the most effective and sustainable tool 197:235 the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea 197:308 For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. 36810563 1 36 theme sustainable 220:230 arg1 resistance 173:182 host resistance 168:182 host resistance 168:182 For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. 36810563 10 37 theme resistant 1651:1659 arg1 TS-specific 1671:1681 TS-specific 1671:1681 TS-specific 1671:1681 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 10 37 theme resistant 1651:1659 arg1 cultivar 1661:1668 the resistant cultivar 1647:1668 the resistant cultivar (TS-specific) 1647:1682 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 2 38 theme underlying 400:409 arg1 mechanisms 411:420 the underlying mechanisms 396:420 the underlying mechanisms 396:420 Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. 36810563 2 39 theme infection 376:384 arg1 phase 367:371 the most critical phase 349:371 the most critical phase of infection 349:384 Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. 36810563 2 39 theme infection 376:384 arg1 attachment 335:344 zoospore root attachment 321:344 zoospore root attachment 321:344 Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. 36810563 8 40 theme cell-wall 1331:1339 arg1 abundant 1427:1434 abundant 1427:1434 abundant 1427:1434 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 8 40 theme cell-wall 1331:1339 arg1 protein 1341:1347 the pathogen-defence-related cell-wall protein 1302:1347 the pathogen-defence-related cell-wall protein 1302:1347 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 4 41 theme cell-wall 654:662 arg1 proteins 664:671 root cell-wall proteins 649:671 root cell-wall proteins 649:671 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 5 42 theme root 809:812 arg1 segments 814:821 root segments 809:821 root segments 809:821 Subsequent analysis of peptides released by trypsin shaving (TS) of root segments identified 262 proteins that were differentially abundant between cultivars. 36810563 7 43 theme specific 1218:1225 arg1 proteins 1209:1216 226 proteins 1205:1216 226 proteins 1205:1216 Comparison with whole-root proteomic analysis of the same cultivars identified 226 proteins specific to the TS dataset, of which 188 were significantly different. 36810563 3 44 theme proteins 527:534 arg1 role 476:479 the potential role 462:479 the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment 462:592 This study investigated the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment. 36810563 3 45 theme potential 466:474 arg1 role 476:479 the potential role 462:479 the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment 462:592 This study investigated the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment. 36810563 6 46 theme intracellular 971:983 arg1 proteins 985:992 intracellular proteins 971:992 intracellular proteins 971:992 These were enriched in root-surface-derived peptides but also included intracellular proteins, e.g., proteins associated with glutathione metabolism and lignin biosynthesis, which were more abundant in the resistant cultivar. 36810563 4 47 theme enzymatic 628:636 arg1 removal 638:644 enzymatic removal 628:644 enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides 628:709 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 7 48 theme cultivars 1184:1192 arg1 analysis 1163:1170 whole-root proteomic analysis 1142:1170 whole-root proteomic analysis of the same cultivars 1142:1192 Comparison with whole-root proteomic analysis of the same cultivars identified 226 proteins specific to the TS dataset, of which 188 were significantly different. 36810563 1 49 theme host 168:171 arg1 resistance 173:182 host resistance 168:182 host resistance 168:182 For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. 36810563 1 49 theme host 168:171 arg1 tool 232:235 the most effective and sustainable tool 197:235 the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea 197:308 For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. 36810563 7 50 theme TS 1234:1235 arg1 dataset 1237:1243 the TS dataset 1230:1243 the TS dataset 1230:1243 Comparison with whole-root proteomic analysis of the same cultivars identified 226 proteins specific to the TS dataset, of which 188 were significantly different. 36810563 4 51 theme polysaccharides 695:709 arg1 removal 638:644 enzymatic removal 628:644 enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides 628:709 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 10 52 theme protein 1695:1701 arg1 endo-1,3-beta-glucosidase 1710:1734 the protein glucan endo-1,3-beta-glucosidase 1691:1734 the protein glucan endo-1,3-beta-glucosidase 1691:1734 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 5 53 theme segments 814:821 arg1 TS 802:803 TS 802:803 TS 802:803 Subsequent analysis of peptides released by trypsin shaving (TS) of root segments identified 262 proteins that were differentially abundant between cultivars. 36810563 5 53 theme segments 814:821 arg1 shaving 793:799 trypsin shaving 785:799 trypsin shaving (TS) of root segments 785:821 Subsequent analysis of peptides released by trypsin shaving (TS) of root segments identified 262 proteins that were differentially abundant between cultivars. 36810563 6 54 from cultivar 1116:1123 arg1 abundant 1090:1097 abundant 1090:1097 abundant 1090:1097 These were enriched in root-surface-derived peptides but also included intracellular proteins, e.g., proteins associated with glutathione metabolism and lignin biosynthesis, which were more abundant in the resistant cultivar. 36810563 2 55 theme root 330:333 arg1 phase 367:371 the most critical phase 349:371 the most critical phase of infection 349:384 Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. 36810563 2 55 theme root 330:333 arg1 attachment 335:344 zoospore root attachment 321:344 zoospore root attachment 321:344 Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. 36810563 9 56 theme TS 1543:1544 arg1 datasets 1561:1568 both the TS and whole-root datasets 1534:1568 datasets 1561:1568 A further major latex protein was reduced in the resistant cultivar in both the TS and whole-root datasets. 36810563 4 57 theme S. 714:715 arg1 attachment 729:738 S. subterranea attachment 714:738 S. subterranea attachment 714:738 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 0 58 theme Scab 136:139 arg1 Disease 141:147 Powdery Scab Disease 128:147 Powdery Scab Disease 128:147 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 9 59 theme whole-root 1550:1559 arg1 datasets 1561:1568 both the TS and whole-root datasets 1534:1568 datasets 1561:1568 A further major latex protein was reduced in the resistant cultivar in both the TS and whole-root datasets. 36810563 8 60 theme kDa 1357:1359 arg1 glycoprotein 1361:1372 stem 28 kDa glycoprotein 1349:1372 stem 28 kDa glycoprotein 1349:1372 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 7 61 theme whole-root 1142:1151 arg1 analysis 1163:1170 whole-root proteomic analysis 1142:1170 whole-root proteomic analysis of the same cultivars 1142:1192 Comparison with whole-root proteomic analysis of the same cultivars identified 226 proteins specific to the TS dataset, of which 188 were significantly different. 36810563 8 62 theme stem 1349:1352 arg1 glycoprotein 1361:1372 stem 28 kDa glycoprotein 1349:1372 stem 28 kDa glycoprotein 1349:1372 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 1 63 theme effective 206:214 arg1 tool 232:235 the most effective and sustainable tool 197:235 the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea 197:308 For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. 36810563 1 63 theme effective 206:214 arg1 resistance 173:182 host resistance 168:182 host resistance 168:182 For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. 36810563 6 64 theme glutathione 1026:1036 arg1 metabolism 1038:1047 glutathione metabolism 1026:1047 glutathione metabolism 1026:1047 These were enriched in root-surface-derived peptides but also included intracellular proteins, e.g., proteins associated with glutathione metabolism and lignin biosynthesis, which were more abundant in the resistant cultivar. 36810563 4 65 theme glycans 683:689 arg1 removal 638:644 enzymatic removal 628:644 enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides 628:709 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 8 66 theme major 1382:1386 arg1 proteins 1394:1401 two major latex proteins 1378:1401 two major latex proteins 1378:1401 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 5 67 theme Subsequent 741:750 arg1 analysis 752:759 Subsequent analysis 741:759 Subsequent analysis of peptides released by trypsin shaving (TS) of root segments 741:821 Subsequent analysis of peptides released by trypsin shaving (TS) of root segments identified 262 proteins that were differentially abundant between cultivars. 36810563 8 68 gly glycoprotein 1361:1372 arg1 glycoprotein 1361:1372 stem 28 kDa glycoprotein 1349:1372 stem 28 kDa glycoprotein 1349:1372 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 6 69 theme resistant 1106:1114 arg1 cultivar 1116:1123 the resistant cultivar 1102:1123 the resistant cultivar 1102:1123 These were enriched in root-surface-derived peptides but also included intracellular proteins, e.g., proteins associated with glutathione metabolism and lignin biosynthesis, which were more abundant in the resistant cultivar. 36810563 11 70 theme zoospore 1882:1889 arg1 binding 1891:1897 zoospore binding 1882:1897 zoospore binding to potato roots and susceptibility to S. subterranea 1882:1950 These results imply a particular role for major latex proteins and glucan endo-1,3-beta-glucosidase in regulating zoospore binding to potato roots and susceptibility to S. subterranea. 36810563 0 71 theme Cultivars 90:98 arg1 Roots 74:78 Roots 74:78 Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease 74:147 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 0 72 theme Powdery 128:134 arg1 Disease 141:147 Powdery Scab Disease 128:147 Powdery Scab Disease 128:147 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 6 73 from abundant 1090:1097 arg1 cultivar 1116:1123 the resistant cultivar 1102:1123 the resistant cultivar 1102:1123 These were enriched in root-surface-derived peptides but also included intracellular proteins, e.g., proteins associated with glutathione metabolism and lignin biosynthesis, which were more abundant in the resistant cultivar. 36810563 5 74 theme trypsin 785:791 arg1 TS 802:803 TS 802:803 TS 802:803 Subsequent analysis of peptides released by trypsin shaving (TS) of root segments identified 262 proteins that were differentially abundant between cultivars. 36810563 5 74 theme trypsin 785:791 arg1 shaving 793:799 trypsin shaving 785:799 trypsin shaving (TS) of root segments 785:821 Subsequent analysis of peptides released by trypsin shaving (TS) of root segments identified 262 proteins that were differentially abundant between cultivars. 36810563 6 75 link root-surface-derived 923:942 arg1 peptides 944:951 root-surface-derived peptides 923:951 root-surface-derived peptides 923:951 These were enriched in root-surface-derived peptides but also included intracellular proteins, e.g., proteins associated with glutathione metabolism and lignin biosynthesis, which were more abundant in the resistant cultivar. 36810563 8 76 from abundant 1427:1434 arg1 cultivar 1453:1460 the resistant cultivar 1439:1460 the resistant cultivar 1439:1460 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 7 77 with Comparison 1126:1135 arg1 analysis 1163:1170 whole-root proteomic analysis 1142:1170 whole-root proteomic analysis of the same cultivars 1142:1192 Comparison with whole-root proteomic analysis of the same cultivars identified 226 proteins specific to the TS dataset, of which 188 were significantly different. 36810563 0 78 theme Spongospora 27:37 arg1 Attachment 60:69 Spongospora subterranea Zoospore Attachment 27:69 Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease 27:147 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 1 79 theme Spongospora 286:296 arg1 subterranea 298:308 the plasmodiophorid Spongospora subterranea 266:308 the plasmodiophorid Spongospora subterranea 266:308 For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. 36810563 9 80 from cultivar 1522:1529 arg1 datasets 1561:1568 both the TS and whole-root datasets 1534:1568 datasets 1561:1568 A further major latex protein was reduced in the resistant cultivar in both the TS and whole-root datasets. 36810563 8 81 dep protein 1341:1347 arg1 glycoprotein 1361:1372 stem 28 kDa glycoprotein 1349:1372 stem 28 kDa glycoprotein 1349:1372 Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. 36810563 0 82 theme Zoospore 51:58 arg1 Attachment 60:69 Spongospora subterranea Zoospore Attachment 27:69 Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease 27:147 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 6 83 theme root-surface-derived 923:942 arg1 peptides 944:951 root-surface-derived peptides 923:951 root-surface-derived peptides 923:951 These were enriched in root-surface-derived peptides but also included intracellular proteins, e.g., proteins associated with glutathione metabolism and lignin biosynthesis, which were more abundant in the resistant cultivar. 36810563 11 84 theme particular 1790:1799 arg1 role 1801:1804 a particular role 1788:1804 a particular role for major latex proteins and glucan endo-1,3-beta-glucosidase in regulating zoospore binding to potato roots and susceptibility to S. subterranea 1788:1950 These results imply a particular role for major latex proteins and glucan endo-1,3-beta-glucosidase in regulating zoospore binding to potato roots and susceptibility to S. subterranea. 36810563 0 85 theme Susceptible 113:123 arg1 Cultivars 90:98 Potato Cultivars 83:98 Potato Cultivars Resistant or Susceptible to Powdery Scab Disease 83:147 Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease. 36810563 9 86 theme further 1465:1471 arg1 protein 1485:1491 A further major latex protein 1463:1491 A further major latex protein 1463:1491 A further major latex protein was reduced in the resistant cultivar in both the TS and whole-root datasets. 36810563 3 87 from role 476:479 arg1 cultivars 539:547 cultivars 539:547 cultivars resistant/susceptible to zoospore attachment 539:592 This study investigated the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment. 36810563 9 88 theme latex 1479:1483 arg1 protein 1485:1491 A further major latex protein 1463:1491 A further major latex protein 1463:1491 A further major latex protein was reduced in the resistant cultivar in both the TS and whole-root datasets. 36810563 10 89 from cultivar 1661:1668 arg1 abundant 1635:1642 abundant 1635:1642 abundant 1635:1642 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 4 90 theme root 649:652 arg1 proteins 664:671 root cell-wall proteins 649:671 root cell-wall proteins 649:671 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 10 91 theme S-transferase 1602:1614 arg1 proteins 1616:1623 three glutathione S-transferase proteins 1584:1623 three glutathione S-transferase proteins 1584:1623 In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. 36810563 11 92 theme latex 1816:1820 arg1 proteins 1822:1829 major latex proteins 1810:1829 major latex proteins 1810:1829 These results imply a particular role for major latex proteins and glucan endo-1,3-beta-glucosidase in regulating zoospore binding to potato roots and susceptibility to S. subterranea. 36810563 3 93 theme cell-wall 497:505 arg1 polysaccharides 507:521 root-surface cell-wall polysaccharides 484:521 root-surface cell-wall polysaccharides 484:521 This study investigated the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment. 36810563 4 94 theme proteins 664:671 arg1 removal 638:644 enzymatic removal 628:644 enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides 628:709 We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. 36810563 3 95 theme resistant/susceptible 549:569 arg1 cultivars 539:547 cultivars 539:547 cultivars resistant/susceptible to zoospore attachment 539:592 This study investigated the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment. 36709809 3 0 located found 396:400 arg1 mori 412:415 Bombyx mori 405:415 Bombyx mori 405:415 We identified 154 fhx family genes in 44 Lepidoptera insects, and seven fhx-Ls were found in Bombyx mori. 36709809 3 0 located found 396:400 arg2 fhx-Ls 384:389 seven fhx-Ls 378:389 seven fhx-Ls 378:389 We identified 154 fhx family genes in 44 Lepidoptera insects, and seven fhx-Ls were found in Bombyx mori. 36709809 7 1 theme fhx-L1 812:817 arg1 mutant 802:807 a homozygous mutant 789:807 a homozygous mutant of fhx-L1 (fhx-L1KO) 789:828 CRISPR/Cas9-mediated gene editing was used to generate a homozygous mutant of fhx-L1 (fhx-L1KO). 36709809 3 2 from genes 341:345 arg1 insects 365:371 44 Lepidoptera insects 350:371 44 Lepidoptera insects 350:371 We identified 154 fhx family genes in 44 Lepidoptera insects, and seven fhx-Ls were found in Bombyx mori. 36709809 2 3 theme fhx 290:292 arg1 homolog 271:277 the homolog 267:277 the homolog of fibroin fhx (fibrohexamerin) 267:309 In this study, we focused on fhx-L1 (fibrohexamerin-like1), which was the homolog of fibroin fhx (fibrohexamerin). 36709809 2 3 theme fhx 290:292 arg1 fhx-L1 226:231 fhx-L1 226:231 fhx-L1 (fibrohexamerin-like1) 226:254 In this study, we focused on fhx-L1 (fibrohexamerin-like1), which was the homolog of fibroin fhx (fibrohexamerin). 36709809 7 4 theme homozygous 791:800 arg1 mutant 802:807 a homozygous mutant 789:807 a homozygous mutant of fhx-L1 (fhx-L1KO) 789:828 CRISPR/Cas9-mediated gene editing was used to generate a homozygous mutant of fhx-L1 (fhx-L1KO). 36709809 9 5 theme fhx-L1KO 1143:1150 arg1 silk 1152:1155 the fhx-L1KO silk 1139:1155 the fhx-L1KO silk 1139:1155 We also found that the content of β-sheet in the mutant silk was lower than in the WT silk, which resulted in further deterioration of the mechanical properties of the fhx-L1KO silk. 36709809 7 6 used used 772:775 arg2 editing 760:766 CRISPR/Cas9-mediated gene editing 734:766 CRISPR/Cas9-mediated gene editing 734:766 CRISPR/Cas9-mediated gene editing was used to generate a homozygous mutant of fhx-L1 (fhx-L1KO). 36709809 11 7 theme protein 1328:1334 arg1 function 1336:1343 silk protein function 1323:1343 silk protein function 1323:1343 Then, our study provided a potential insight for in-depth study of silk protein function. 36709809 0 8 theme Bombyx 73:78 arg1 mori 80:83 Bombyx mori 73:83 Bombyx mori 73:83 Identification and functional study of fhx-L1, a major silk component in Bombyx mori. 36709809 9 9 theme silk 1152:1155 arg1 properties 1125:1134 the mechanical properties 1110:1134 the mechanical properties of the fhx-L1KO silk 1110:1155 We also found that the content of β-sheet in the mutant silk was lower than in the WT silk, which resulted in further deterioration of the mechanical properties of the fhx-L1KO silk. 36709809 6 10 theme oligosaccharide 710:724 arg1 chains 726:731 N-linked oligosaccharide chains 701:731 N-linked oligosaccharide chains 701:731 Western blotting revealed that the fhx-L1 protein contains N-linked oligosaccharide chains. 36709809 1 11 theme silkworm 90:97 arg1 cocoon 99:104 The silkworm cocoon 86:104 The silkworm cocoon 86:104 The silkworm cocoon was composed of fibroins, sericins, protease inhibitors, and proteins of unknown function. 36709809 5 12 theme Immunofluorescence 523:540 arg1 analysis 542:549 Immunofluorescence analysis 523:549 Immunofluorescence analysis 523:549 Immunofluorescence analysis showed that fhx-L1 was secreted into the whole sericin layers, similar to sericin1 (ser1). 36709809 6 13 theme N-linked 701:708 arg1 chains 726:731 N-linked oligosaccharide chains 701:731 N-linked oligosaccharide chains 701:731 Western blotting revealed that the fhx-L1 protein contains N-linked oligosaccharide chains. 36709809 6 14 contain contains 692:699 arg1 protein 684:690 the fhx-L1 protein 673:690 the fhx-L1 protein 673:690 Western blotting revealed that the fhx-L1 protein contains N-linked oligosaccharide chains. 36709809 6 14 contain contains 692:699 arg2 chains 726:731 N-linked oligosaccharide chains 701:731 N-linked oligosaccharide chains 701:731 Western blotting revealed that the fhx-L1 protein contains N-linked oligosaccharide chains. 36709809 1 15 theme protease 142:149 arg1 inhibitors 151:160 protease inhibitors 142:160 protease inhibitors 142:160 The silkworm cocoon was composed of fibroins, sericins, protease inhibitors, and proteins of unknown function. 36709809 9 16 theme WT 1058:1059 arg1 silk 1061:1064 the WT silk 1054:1064 the WT silk 1054:1064 We also found that the content of β-sheet in the mutant silk was lower than in the WT silk, which resulted in further deterioration of the mechanical properties of the fhx-L1KO silk. 36709809 8 17 dep wild-type 895:903 arg1 WT 906:907 WT 906:907 WT 906:907 The cocoon of fhx-L1KO was larger and fluffier than that of the wild-type (WT), which was attributed to the lower adhesion between silk fibers. 36709809 4 18 from silk 468:471 arg1 Fhx-L1 418:423 Fhx-L1 418:423 Fhx-L1 418:423 Fhx-L1 was the most abundant of these proteins in silk and was specifically expressed in the silk gland. 36709809 4 18 from silk 468:471 arg1 abundant 438:445 abundant 438:445 abundant 438:445 Fhx-L1 was the most abundant of these proteins in silk and was specifically expressed in the silk gland. 36709809 11 19 theme potential 1283:1291 arg1 insight 1293:1299 a potential insight 1281:1299 a potential insight for in-depth study of silk protein function 1281:1343 Then, our study provided a potential insight for in-depth study of silk protein function. 36709809 8 20 theme lower 939:943 arg1 adhesion 945:952 the lower adhesion 935:952 the lower adhesion between silk fibers 935:972 The cocoon of fhx-L1KO was larger and fluffier than that of the wild-type (WT), which was attributed to the lower adhesion between silk fibers. 36709809 6 21 theme fhx-L1 677:682 arg1 protein 684:690 the fhx-L1 protein 673:690 the fhx-L1 protein 673:690 Western blotting revealed that the fhx-L1 protein contains N-linked oligosaccharide chains. 36709809 3 22 theme Lepidoptera 353:363 arg1 insects 365:371 44 Lepidoptera insects 350:371 44 Lepidoptera insects 350:371 We identified 154 fhx family genes in 44 Lepidoptera insects, and seven fhx-Ls were found in Bombyx mori. 36709809 4 23 theme proteins 456:463 arg1 Fhx-L1 418:423 Fhx-L1 418:423 Fhx-L1 418:423 Fhx-L1 was the most abundant of these proteins in silk and was specifically expressed in the silk gland. 36709809 4 23 theme proteins 456:463 arg1 abundant 438:445 abundant 438:445 abundant 438:445 Fhx-L1 was the most abundant of these proteins in silk and was specifically expressed in the silk gland. 36709809 8 24 theme silk 962:965 arg1 fibers 967:972 silk fibers 962:972 silk fibers 962:972 The cocoon of fhx-L1KO was larger and fluffier than that of the wild-type (WT), which was attributed to the lower adhesion between silk fibers. 36709809 4 25 from abundant 438:445 arg1 silk 468:471 silk 468:471 silk 468:471 Fhx-L1 was the most abundant of these proteins in silk and was specifically expressed in the silk gland. 36709809 0 26 theme functional 19:28 arg1 study 30:34 functional study 19:34 functional study 19:34 Identification and functional study of fhx-L1, a major silk component in Bombyx mori. 36709809 5 27 theme similar 614:620 arg1 layers 606:611 the whole sericin layers 588:611 the whole sericin layers 588:611 Immunofluorescence analysis showed that fhx-L1 was secreted into the whole sericin layers, similar to sericin1 (ser1). 36709809 9 28 theme further 1085:1091 arg1 deterioration 1093:1105 further deterioration 1085:1105 further deterioration of the mechanical properties of the fhx-L1KO silk 1085:1155 We also found that the content of β-sheet in the mutant silk was lower than in the WT silk, which resulted in further deterioration of the mechanical properties of the fhx-L1KO silk. 36709809 10 29 dep properties 1181:1190 arg1 the 1177:1179 the 1177:1179 the 1177:1179 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 7 30 theme CRISPR/Cas9-mediated 734:753 arg1 editing 760:766 CRISPR/Cas9-mediated gene editing 734:766 CRISPR/Cas9-mediated gene editing 734:766 CRISPR/Cas9-mediated gene editing was used to generate a homozygous mutant of fhx-L1 (fhx-L1KO). 36709809 0 31 theme fhx-L1 39:44 arg1 component 60:68 a major silk component 47:68 a major silk component in Bombyx mori 47:83 Identification and functional study of fhx-L1, a major silk component in Bombyx mori. 36709809 0 31 theme fhx-L1 39:44 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and functional study of fhx-L1, a major silk component in Bombyx mori. 36709809 0 31 theme fhx-L1 39:44 arg1 study 30:34 functional study 19:34 functional study 19:34 Identification and functional study of fhx-L1, a major silk component in Bombyx mori. 36709809 0 32 from component 60:68 arg1 mori 80:83 Bombyx mori 73:83 Bombyx mori 73:83 Identification and functional study of fhx-L1, a major silk component in Bombyx mori. 36709809 9 33 from content 998:1004 arg1 silk 1031:1034 the mutant silk 1020:1034 the mutant silk 1020:1034 We also found that the content of β-sheet in the mutant silk was lower than in the WT silk, which resulted in further deterioration of the mechanical properties of the fhx-L1KO silk. 36709809 7 34 theme gene 755:758 arg1 editing 760:766 CRISPR/Cas9-mediated gene editing 734:766 CRISPR/Cas9-mediated gene editing 734:766 CRISPR/Cas9-mediated gene editing was used to generate a homozygous mutant of fhx-L1 (fhx-L1KO). 36709809 1 35 theme unknown 179:185 arg1 function 187:194 unknown function 179:194 unknown function 179:194 The silkworm cocoon was composed of fibroins, sericins, protease inhibitors, and proteins of unknown function. 36709809 3 36 theme fhx 330:332 arg1 genes 341:345 154 fhx family genes 326:345 154 fhx family genes in 44 Lepidoptera insects 326:371 We identified 154 fhx family genes in 44 Lepidoptera insects, and seven fhx-Ls were found in Bombyx mori. 36709809 6 37 link N-linked 701:708 arg1 chains 726:731 N-linked oligosaccharide chains 701:731 N-linked oligosaccharide chains 701:731 Western blotting revealed that the fhx-L1 protein contains N-linked oligosaccharide chains. 36709809 2 38 theme fibroin 282:288 arg1 fibrohexamerin 295:308 fibrohexamerin 295:308 fibrohexamerin 295:308 In this study, we focused on fhx-L1 (fibrohexamerin-like1), which was the homolog of fibroin fhx (fibrohexamerin). 36709809 2 38 theme fibroin 282:288 arg1 fhx 290:292 fibroin fhx 282:292 fibroin fhx (fibrohexamerin) 282:309 In this study, we focused on fhx-L1 (fibrohexamerin-like1), which was the homolog of fibroin fhx (fibrohexamerin). 36709809 3 39 theme Bombyx 405:410 arg1 mori 412:415 Bombyx mori 405:415 Bombyx mori 405:415 We identified 154 fhx family genes in 44 Lepidoptera insects, and seven fhx-Ls were found in Bombyx mori. 36709809 3 40 theme family 334:339 arg1 genes 341:345 154 fhx family genes 326:345 154 fhx family genes in 44 Lepidoptera insects 326:371 We identified 154 fhx family genes in 44 Lepidoptera insects, and seven fhx-Ls were found in Bombyx mori. 36709809 10 41 theme structural 1226:1235 arg1 properties 1181:1190 properties 1181:1190 properties 1181:1190 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 10 41 theme structural 1226:1235 arg1 component 1237:1245 a major structural component 1218:1245 a major structural component in silk 1218:1253 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 10 41 theme structural 1226:1235 arg1 function 1196:1203 function 1196:1203 function 1196:1203 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 5 42 theme whole 592:596 arg1 layers 606:611 the whole sericin layers 588:611 the whole sericin layers 588:611 Immunofluorescence analysis showed that fhx-L1 was secreted into the whole sericin layers, similar to sericin1 (ser1). 36709809 8 43 theme fhx-L1KO 845:852 arg1 larger 858:863 larger 858:863 larger 858:863 The cocoon of fhx-L1KO was larger and fluffier than that of the wild-type (WT), which was attributed to the lower adhesion between silk fibers. 36709809 8 43 theme fhx-L1KO 845:852 arg1 cocoon 835:840 The cocoon 831:840 The cocoon of fhx-L1KO 831:852 The cocoon of fhx-L1KO was larger and fluffier than that of the wild-type (WT), which was attributed to the lower adhesion between silk fibers. 36709809 5 44 theme sericin 598:604 arg1 layers 606:611 the whole sericin layers 588:611 the whole sericin layers 588:611 Immunofluorescence analysis showed that fhx-L1 was secreted into the whole sericin layers, similar to sericin1 (ser1). 36709809 6 45 theme Western 642:648 arg1 blotting 650:657 Western blotting 642:657 Western blotting 642:657 Western blotting revealed that the fhx-L1 protein contains N-linked oligosaccharide chains. 36709809 10 46 from component 1237:1245 arg1 silk 1250:1253 silk 1250:1253 silk 1250:1253 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 11 47 theme silk 1323:1326 arg1 function 1336:1343 silk protein function 1323:1343 silk protein function 1323:1343 Then, our study provided a potential insight for in-depth study of silk protein function. 36709809 4 48 theme silk 511:514 arg1 gland 516:520 the silk gland 507:520 the silk gland 507:520 Fhx-L1 was the most abundant of these proteins in silk and was specifically expressed in the silk gland. 36709809 9 49 theme β-sheet 1009:1015 arg1 content 998:1004 the content 994:1004 the content of β-sheet in the mutant silk 994:1034 We also found that the content of β-sheet in the mutant silk was lower than in the WT silk, which resulted in further deterioration of the mechanical properties of the fhx-L1KO silk. 36709809 9 49 theme β-sheet 1009:1015 arg1 lower 1040:1044 lower 1040:1044 lower 1040:1044 We also found that the content of β-sheet in the mutant silk was lower than in the WT silk, which resulted in further deterioration of the mechanical properties of the fhx-L1KO silk. 36709809 11 50 theme in-depth 1305:1312 arg1 study 1314:1318 in-depth study 1305:1318 in-depth study of silk protein function 1305:1343 Then, our study provided a potential insight for in-depth study of silk protein function. 36709809 0 51 theme silk 55:58 arg1 component 60:68 a major silk component 47:68 a major silk component in Bombyx mori 47:83 Identification and functional study of fhx-L1, a major silk component in Bombyx mori. 36709809 0 51 theme silk 55:58 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and functional study of fhx-L1, a major silk component in Bombyx mori. 36709809 9 52 theme mechanical 1114:1123 arg1 properties 1125:1134 the mechanical properties 1110:1134 the mechanical properties of the fhx-L1KO silk 1110:1155 We also found that the content of β-sheet in the mutant silk was lower than in the WT silk, which resulted in further deterioration of the mechanical properties of the fhx-L1KO silk. 36709809 11 53 theme function 1336:1343 arg1 study 1314:1318 in-depth study 1305:1318 in-depth study of silk protein function 1305:1343 Then, our study provided a potential insight for in-depth study of silk protein function. 36709809 10 54 theme fhx-L1 1208:1213 arg1 properties 1181:1190 properties 1181:1190 properties 1181:1190 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 10 54 theme fhx-L1 1208:1213 arg1 component 1237:1245 a major structural component 1218:1245 a major structural component in silk 1218:1253 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 10 54 theme fhx-L1 1208:1213 arg1 function 1196:1203 function 1196:1203 function 1196:1203 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 10 55 theme major 1220:1224 arg1 properties 1181:1190 properties 1181:1190 properties 1181:1190 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 10 55 theme major 1220:1224 arg1 component 1237:1245 a major structural component 1218:1245 a major structural component in silk 1218:1253 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 10 55 theme major 1220:1224 arg1 function 1196:1203 function 1196:1203 function 1196:1203 Our study revealed the properties and function of fhx-L1 as a major structural component in silk. 36709809 0 56 theme major 49:53 arg1 component 60:68 a major silk component 47:68 a major silk component in Bombyx mori 47:83 Identification and functional study of fhx-L1, a major silk component in Bombyx mori. 36709809 0 56 theme major 49:53 arg1 Identification 0:13 Identification 0:13 Identification 0:13 Identification and functional study of fhx-L1, a major silk component in Bombyx mori. 36709809 9 57 theme properties 1125:1134 arg1 deterioration 1093:1105 further deterioration 1085:1105 further deterioration of the mechanical properties of the fhx-L1KO silk 1085:1155 We also found that the content of β-sheet in the mutant silk was lower than in the WT silk, which resulted in further deterioration of the mechanical properties of the fhx-L1KO silk. 36709809 9 58 theme mutant 1024:1029 arg1 silk 1031:1034 the mutant silk 1020:1034 the mutant silk 1020:1034 We also found that the content of β-sheet in the mutant silk was lower than in the WT silk, which resulted in further deterioration of the mechanical properties of the fhx-L1KO silk. 36709809 1 59 theme function 187:194 arg1 inhibitors 151:160 protease inhibitors 142:160 protease inhibitors 142:160 The silkworm cocoon was composed of fibroins, sericins, protease inhibitors, and proteins of unknown function. 36709809 1 59 theme function 187:194 arg1 fibroins 122:129 fibroins 122:129 fibroins 122:129 The silkworm cocoon was composed of fibroins, sericins, protease inhibitors, and proteins of unknown function. 36709809 1 59 theme function 187:194 arg1 sericins 132:139 sericins 132:139 sericins 132:139 The silkworm cocoon was composed of fibroins, sericins, protease inhibitors, and proteins of unknown function. 36709809 1 59 theme function 187:194 arg1 proteins 167:174 proteins 167:174 proteins of unknown function 167:194 The silkworm cocoon was composed of fibroins, sericins, protease inhibitors, and proteins of unknown function. 36621663 8 0 theme FXYD5 1340:1344 arg1 protein 1368:1374 the target protein 1357:1374 the target protein of mAb 12-13.8 1357:1389 We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. 36621663 8 0 theme FXYD5 1340:1344 arg1 protein 1346:1352 the FXYD5 protein 1336:1352 the FXYD5 protein 1336:1352 We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. 36621663 4 1 theme human 686:690 arg1 PaCa-2 cells 714:725 human pancreatic cancer MIA PaCa-2 cells 686:725 human pancreatic cancer MIA PaCa-2 cells 686:725 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 7 2 theme tumor 1134:1138 arg1 tissues 1140:1146 pancreatic and lung tumor tissues 1114:1146 tissues 1140:1146 Immunohistochemical staining of pancreatic and lung tumor tissues indicated that the increase of the staining strength by mAb 12-13.8 positively and inversely correlated with the patients' cancer recurrence and survival rate, respectively. 36621663 4 3 theme cancer 703:708 arg1 PaCa-2 cells 714:725 human pancreatic cancer MIA PaCa-2 cells 686:725 human pancreatic cancer MIA PaCa-2 cells 686:725 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 4 4 theme monoclonal 769:778 arg1 mAb 790:792 mAb 790:792 mAb 790:792 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 4 4 theme monoclonal 769:778 arg1 antibody 780:787 a monoclonal antibody 767:787 a monoclonal antibody (mAb) 767:793 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 5 5 theme flow 918:921 arg1 cytometry 923:931 flow cytometry 918:931 flow cytometry 918:931 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 7 6 theme tissues 1140:1146 arg1 staining 1102:1109 Immunohistochemical staining 1082:1109 Immunohistochemical staining of pancreatic and lung tumor tissues 1082:1146 Immunohistochemical staining of pancreatic and lung tumor tissues indicated that the increase of the staining strength by mAb 12-13.8 positively and inversely correlated with the patients' cancer recurrence and survival rate, respectively. 36621663 1 7 theme cancer 150:155 arg1 treatments 157:166 cancer treatments 150:166 cancer treatments 150:166 Despite recent advances in cancer treatments, pancreatic cancer has a dismal prognosis globally. 36621663 10 8 theme FXYD5 1572:1576 arg1 protein 1578:1584 the FXYD5 protein 1568:1584 the FXYD5 protein 1568:1584 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 8 9 theme array 1411:1415 arg1 system 1427:1432 a human protein array screening system 1395:1432 a human protein array screening system 1395:1432 We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. 36621663 2 10 theme recalcitrant 281:292 arg1 tumors 294:299 recalcitrant tumors 281:299 recalcitrant tumors 281:299 Early detection of cancer cells and effective treatments for recalcitrant tumors are required, but the innovative therapeutic tools remain in development. 36621663 9 11 mod modified 1504:1511 arg1 protein 1445:1451 The FXYD5 protein 1435:1451 The FXYD5 protein 1435:1451 The FXYD5 protein is overexpressed in various types of cancer and is modified by O-linked glycosylation. 36621663 9 11 mod modified 1504:1511 arg3 glycosylation 1525:1537 O-linked glycosylation 1516:1537 O-linked glycosylation 1516:1537 The FXYD5 protein is overexpressed in various types of cancer and is modified by O-linked glycosylation. 36621663 10 12 dep residues 1694:1701 arg1 45-52 1703:1707 45-52 1703:1707 45-52 1703:1707 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 7 13 theme lung 1129:1132 arg1 tissues 1140:1146 pancreatic and lung tumor tissues 1114:1146 tissues 1140:1146 Immunohistochemical staining of pancreatic and lung tumor tissues indicated that the increase of the staining strength by mAb 12-13.8 positively and inversely correlated with the patients' cancer recurrence and survival rate, respectively. 36621663 11 14 from delivery 1858:1865 arg1 useful 1828:1833 useful 1828:1833 useful 1828:1833 Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients. 36621663 9 15 theme O-linked 1516:1523 arg1 glycosylation 1525:1537 O-linked glycosylation 1516:1537 O-linked glycosylation 1516:1537 The FXYD5 protein is overexpressed in various types of cancer and is modified by O-linked glycosylation. 36621663 10 16 theme acid 1689:1692 arg1 residues 1694:1701 amino acid residues 45-52 1683:1707 amino acid residues 45-52 1683:1707 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 10 16 theme acid 1689:1692 arg1 sequence 1732:1739 the minimal peptide sequence 1712:1739 the minimal peptide sequence 1712:1739 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 7 17 theme survival 1293:1300 arg1 rate 1302:1305 survival rate 1293:1305 survival rate 1293:1305 Immunohistochemical staining of pancreatic and lung tumor tissues indicated that the increase of the staining strength by mAb 12-13.8 positively and inversely correlated with the patients' cancer recurrence and survival rate, respectively. 36621663 1 18 from advances 138:145 arg1 treatments 157:166 cancer treatments 150:166 cancer treatments 150:166 Despite recent advances in cancer treatments, pancreatic cancer has a dismal prognosis globally. 36621663 6 19 theme cancer-bearing 1061:1074 arg1 mice 1076:1079 cancer-bearing mice 1061:1079 cancer-bearing mice 1061:1079 In addition, we showed that mAb 12-13.8 could accumulate in tumors, through in vivo experiments using cancer-bearing mice. 36621663 5 20 theme molecular 840:848 arg1 cytometry 923:931 flow cytometry 918:931 flow cytometry 918:931 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 5 20 theme molecular 840:848 arg1 immunoblotting 902:915 immunoblotting 902:915 immunoblotting 902:915 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 5 20 theme molecular 840:848 arg1 experiments 861:871 molecular biological experiments 840:871 molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation 840:956 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 5 20 theme molecular 840:848 arg1 immunoprecipitation 938:956 immunoprecipitation 938:956 immunoprecipitation 938:956 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 5 20 theme molecular 840:848 arg1 immunocytochemistry 881:899 immunocytochemistry 881:899 immunocytochemistry 881:899 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 0 21 theme pancreatic 95:104 arg1 cancer 115:120 pancreatic and lung cancer 95:120 cancer 115:120 Generation of the novel anti-FXYD5 monoclonal antibody and its application to the diagnosis of pancreatic and lung cancer. 36621663 3 22 contain have 496:499 arg2 potential 501:509 potential 501:509 potential 501:509 Cancer-specific antigens expressed only on cancer cells may help resolve these problems, and antibodies to such antigens have potential in basic research and clinical applications. 36621663 3 22 contain have 496:499 arg1 antibodies 468:477 antibodies 468:477 antibodies to such antigens 468:494 Cancer-specific antigens expressed only on cancer cells may help resolve these problems, and antibodies to such antigens have potential in basic research and clinical applications. 36621663 0 23 theme monoclonal 35:44 arg1 antibody 46:53 the novel anti-FXYD5 monoclonal antibody 14:53 the novel anti-FXYD5 monoclonal antibody 14:53 Generation of the novel anti-FXYD5 monoclonal antibody and its application to the diagnosis of pancreatic and lung cancer. 36621663 6 24 dep in 1035:1036 arg1 vivo 1038:1041 vivo 1038:1041 vivo 1038:1041 In addition, we showed that mAb 12-13.8 could accumulate in tumors, through in vivo experiments using cancer-bearing mice. 36621663 2 25 theme effective 256:264 arg1 treatments 266:275 effective treatments 256:275 effective treatments for recalcitrant tumors 256:299 Early detection of cancer cells and effective treatments for recalcitrant tumors are required, but the innovative therapeutic tools remain in development. 36621663 5 26 theme biological 850:859 arg1 cytometry 923:931 flow cytometry 918:931 flow cytometry 918:931 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 5 26 theme biological 850:859 arg1 immunoblotting 902:915 immunoblotting 902:915 immunoblotting 902:915 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 5 26 theme biological 850:859 arg1 experiments 861:871 molecular biological experiments 840:871 molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation 840:956 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 5 26 theme biological 850:859 arg1 immunoprecipitation 938:956 immunoprecipitation 938:956 immunoprecipitation 938:956 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 5 26 theme biological 850:859 arg1 immunocytochemistry 881:899 immunocytochemistry 881:899 immunocytochemistry 881:899 This antibody was applied to molecular biological experiments such as immunocytochemistry, immunoblotting, flow cytometry, and immunoprecipitation. 36621663 7 27 theme staining 1183:1190 arg1 strength 1192:1199 the staining strength 1179:1199 the staining strength 1179:1199 Immunohistochemical staining of pancreatic and lung tumor tissues indicated that the increase of the staining strength by mAb 12-13.8 positively and inversely correlated with the patients' cancer recurrence and survival rate, respectively. 36621663 4 28 theme specific 568:575 arg1 antibodies 577:586 specific antibodies 568:586 specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells 568:660 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 7 29 theme Immunohistochemical 1082:1100 arg1 staining 1102:1109 Immunohistochemical staining 1082:1109 Immunohistochemical staining of pancreatic and lung tumor tissues 1082:1146 Immunohistochemical staining of pancreatic and lung tumor tissues indicated that the increase of the staining strength by mAb 12-13.8 positively and inversely correlated with the patients' cancer recurrence and survival rate, respectively. 36621663 11 30 from useful 1828:1833 arg1 diagnostic 1838:1847 diagnostic 1838:1847 diagnostic 1838:1847 Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients. 36621663 11 30 from useful 1828:1833 arg1 delivery 1858:1865 drug delivery 1853:1865 drug delivery 1853:1865 Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients. 36621663 8 31 theme mAb 1379:1381 arg1 protein 1368:1374 the target protein 1357:1374 the target protein of mAb 12-13.8 1357:1389 We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. 36621663 8 31 theme mAb 1379:1381 arg1 protein 1346:1352 the FXYD5 protein 1336:1352 the FXYD5 protein 1336:1352 We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. 36621663 11 32 theme useful 1828:1833 arg1 applications 1867:1878 useful in diagnostic and drug delivery applications 1828:1878 useful in diagnostic and drug delivery applications for cancer patients 1828:1898 Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients. 36621663 1 33 theme pancreatic 169:178 arg1 cancer 180:185 pancreatic cancer 169:185 pancreatic cancer 169:185 Despite recent advances in cancer treatments, pancreatic cancer has a dismal prognosis globally. 36621663 7 34 theme strength 1192:1199 arg1 increase 1167:1174 the increase 1163:1174 the increase of the staining strength by mAb 12-13.8 1163:1214 Immunohistochemical staining of pancreatic and lung tumor tissues indicated that the increase of the staining strength by mAb 12-13.8 positively and inversely correlated with the patients' cancer recurrence and survival rate, respectively. 36621663 11 35 theme valuable 1791:1798 arg1 mAb 1768:1770 mAb 12-13.8 1768:1778 mAb 12-13.8 1768:1778 Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients. 36621663 11 35 theme valuable 1791:1798 arg1 tool 1800:1803 a valuable tool 1789:1803 a valuable tool for FXYD5 studies 1789:1821 Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients. 36621663 11 36 theme cancer 1884:1889 arg1 patients 1891:1898 cancer patients 1884:1898 cancer patients 1884:1898 Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients. 36621663 0 37 theme novel 18:22 arg1 antibody 46:53 the novel anti-FXYD5 monoclonal antibody 14:53 the novel anti-FXYD5 monoclonal antibody 14:53 Generation of the novel anti-FXYD5 monoclonal antibody and its application to the diagnosis of pancreatic and lung cancer. 36621663 0 38 theme cancer 115:120 arg1 diagnosis 82:90 the diagnosis 78:90 the diagnosis of pancreatic and lung cancer 78:120 Generation of the novel anti-FXYD5 monoclonal antibody and its application to the diagnosis of pancreatic and lung cancer. 36621663 8 39 theme human 1397:1401 arg1 system 1427:1432 a human protein array screening system 1395:1432 a human protein array screening system 1395:1432 We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. 36621663 6 40 theme in 1035:1036 arg1 experiments 1043:1053 in vivo experiments 1035:1053 in vivo experiments using cancer-bearing mice 1035:1079 In addition, we showed that mAb 12-13.8 could accumulate in tumors, through in vivo experiments using cancer-bearing mice. 36621663 4 41 theme pancreatic 638:647 arg1 cells 656:660 pancreatic cancer cells 638:660 pancreatic cancer cells 638:660 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 3 42 theme Cancer-specific 375:389 arg1 antigens 391:398 Cancer-specific antigens 375:398 Cancer-specific antigens expressed only on cancer cells 375:429 Cancer-specific antigens expressed only on cancer cells may help resolve these problems, and antibodies to such antigens have potential in basic research and clinical applications. 36621663 9 43 theme various 1473:1479 arg1 types 1481:1485 various types 1473:1485 various types of cancer 1473:1495 The FXYD5 protein is overexpressed in various types of cancer and is modified by O-linked glycosylation. 36621663 0 44 theme lung 110:113 arg1 cancer 115:120 pancreatic and lung cancer 95:120 cancer 115:120 Generation of the novel anti-FXYD5 monoclonal antibody and its application to the diagnosis of pancreatic and lung cancer. 36621663 4 45 with mice 676:679 arg1 PaCa-2 cells 714:725 human pancreatic cancer MIA PaCa-2 cells 686:725 human pancreatic cancer MIA PaCa-2 cells 686:725 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 4 46 theme pancreatic 692:701 arg1 PaCa-2 cells 714:725 human pancreatic cancer MIA PaCa-2 cells 686:725 human pancreatic cancer MIA PaCa-2 cells 686:725 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 3 47 theme basic 514:518 arg1 research 520:527 basic research 514:527 basic research 514:527 Cancer-specific antigens expressed only on cancer cells may help resolve these problems, and antibodies to such antigens have potential in basic research and clinical applications. 36621663 3 48 theme cancer 418:423 arg1 cells 425:429 cancer cells 418:429 cancer cells 418:429 Cancer-specific antigens expressed only on cancer cells may help resolve these problems, and antibodies to such antigens have potential in basic research and clinical applications. 36621663 4 49 theme MIA 710:712 arg1 PaCa-2 cells 714:725 human pancreatic cancer MIA PaCa-2 cells 686:725 human pancreatic cancer MIA PaCa-2 cells 686:725 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 9 50 theme cancer 1490:1495 arg1 types 1481:1485 various types 1473:1485 various types of cancer 1473:1495 The FXYD5 protein is overexpressed in various types of cancer and is modified by O-linked glycosylation. 36621663 4 51 theme cells 656:660 arg1 surface 627:633 the surface 623:633 the surface of pancreatic cancer cells 623:660 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 1 52 theme dismal 193:198 arg1 prognosis 200:208 a dismal prognosis 191:208 a dismal prognosis 191:208 Despite recent advances in cancer treatments, pancreatic cancer has a dismal prognosis globally. 36621663 0 53 theme anti-FXYD5 24:33 arg1 antibody 46:53 the novel anti-FXYD5 monoclonal antibody 14:53 the novel anti-FXYD5 monoclonal antibody 14:53 Generation of the novel anti-FXYD5 monoclonal antibody and its application to the diagnosis of pancreatic and lung cancer. 36621663 10 54 theme FXYD5-knockout 1610:1623 arg1 PaCa-2 cells 1629:1640 FXYD5-knockout MIA PaCa-2 cells 1610:1640 FXYD5-knockout MIA PaCa-2 cells 1610:1640 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 2 55 theme Early 220:224 arg1 detection 226:234 Early detection 220:234 Early detection of cancer cells 220:250 Early detection of cancer cells and effective treatments for recalcitrant tumors are required, but the innovative therapeutic tools remain in development. 36621663 4 56 theme cancer 649:654 arg1 cells 656:660 pancreatic cancer cells 638:660 pancreatic cancer cells 638:660 To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12-13.8. 36621663 10 57 theme peptide 1724:1730 arg1 residues 1694:1701 amino acid residues 45-52 1683:1707 amino acid residues 45-52 1683:1707 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 10 57 theme peptide 1724:1730 arg1 sequence 1732:1739 the minimal peptide sequence 1712:1739 the minimal peptide sequence 1712:1739 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 8 58 theme protein 1403:1409 arg1 system 1427:1432 a human protein array screening system 1395:1432 a human protein array screening system 1395:1432 We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. 36621663 2 59 theme therapeutic 334:344 arg1 tools 346:350 the innovative therapeutic tools 319:350 the innovative therapeutic tools 319:350 Early detection of cancer cells and effective treatments for recalcitrant tumors are required, but the innovative therapeutic tools remain in development. 36621663 0 60 theme antibody 46:53 arg1 Generation 0:9 Generation 0:9 Generation of the novel anti-FXYD5 monoclonal antibody 0:53 Generation of the novel anti-FXYD5 monoclonal antibody and its application to the diagnosis of pancreatic and lung cancer. 36621663 0 60 theme antibody 46:53 arg1 application 63:73 its application 59:73 its application to the diagnosis of pancreatic and lung cancer 59:120 Generation of the novel anti-FXYD5 monoclonal antibody and its application to the diagnosis of pancreatic and lung cancer. 36621663 9 61 link O-linked 1516:1523 arg1 glycosylation 1525:1537 O-linked glycosylation 1516:1537 O-linked glycosylation 1516:1537 The FXYD5 protein is overexpressed in various types of cancer and is modified by O-linked glycosylation. 36621663 7 62 theme pancreatic 1114:1123 arg1 tissues 1140:1146 pancreatic and lung tumor tissues 1114:1146 tissues 1140:1146 Immunohistochemical staining of pancreatic and lung tumor tissues indicated that the increase of the staining strength by mAb 12-13.8 positively and inversely correlated with the patients' cancer recurrence and survival rate, respectively. 36621663 2 63 theme innovative 323:332 arg1 tools 346:350 the innovative therapeutic tools 319:350 the innovative therapeutic tools 319:350 Early detection of cancer cells and effective treatments for recalcitrant tumors are required, but the innovative therapeutic tools remain in development. 36621663 11 64 theme FXYD5 1809:1813 arg1 studies 1815:1821 FXYD5 studies 1809:1821 FXYD5 studies 1809:1821 Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients. 36621663 10 65 theme MIA 1625:1627 arg1 PaCa-2 cells 1629:1640 FXYD5-knockout MIA PaCa-2 cells 1610:1640 FXYD5-knockout MIA PaCa-2 cells 1610:1640 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 8 66 theme screening 1417:1425 arg1 system 1427:1432 a human protein array screening system 1395:1432 a human protein array screening system 1395:1432 We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. 36621663 8 67 theme target 1361:1366 arg1 protein 1368:1374 the target protein 1357:1374 the target protein of mAb 12-13.8 1357:1389 We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. 36621663 8 67 theme target 1361:1366 arg1 protein 1346:1352 the FXYD5 protein 1336:1352 the FXYD5 protein 1336:1352 We identified the FXYD5 protein as the target protein of mAb 12-13.8, by a human protein array screening system. 36621663 10 68 theme minimal 1716:1722 arg1 residues 1694:1701 amino acid residues 45-52 1683:1707 amino acid residues 45-52 1683:1707 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 10 68 theme minimal 1716:1722 arg1 sequence 1732:1739 the minimal peptide sequence 1712:1739 the minimal peptide sequence 1712:1739 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 3 69 theme clinical 533:540 arg1 applications 542:553 clinical applications 533:553 clinical applications 533:553 Cancer-specific antigens expressed only on cancer cells may help resolve these problems, and antibodies to such antigens have potential in basic research and clinical applications. 36621663 2 70 theme cells 246:250 arg1 detection 226:234 Early detection 220:234 Early detection of cancer cells 220:250 Early detection of cancer cells and effective treatments for recalcitrant tumors are required, but the innovative therapeutic tools remain in development. 36621663 2 70 theme cells 246:250 arg1 treatments 266:275 effective treatments 256:275 effective treatments for recalcitrant tumors 256:299 Early detection of cancer cells and effective treatments for recalcitrant tumors are required, but the innovative therapeutic tools remain in development. 36621663 10 71 theme epitope 1656:1662 arg1 mapping 1664:1670 detailed epitope mapping 1647:1670 detailed epitope mapping 1647:1670 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 3 72 theme such 482:485 arg1 antigens 487:494 such antigens 482:494 such antigens 482:494 Cancer-specific antigens expressed only on cancer cells may help resolve these problems, and antibodies to such antigens have potential in basic research and clinical applications. 36621663 11 73 from diagnostic 1838:1847 arg1 useful 1828:1833 useful 1828:1833 useful 1828:1833 Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients. 36621663 1 74 contain has 187:189 arg2 prognosis 200:208 a dismal prognosis 191:208 a dismal prognosis 191:208 Despite recent advances in cancer treatments, pancreatic cancer has a dismal prognosis globally. 36621663 1 74 contain has 187:189 arg1 cancer 180:185 pancreatic cancer 169:185 pancreatic cancer 169:185 Despite recent advances in cancer treatments, pancreatic cancer has a dismal prognosis globally. 36621663 2 75 theme cancer 239:244 arg1 cells 246:250 cancer cells 239:250 cancer cells 239:250 Early detection of cancer cells and effective treatments for recalcitrant tumors are required, but the innovative therapeutic tools remain in development. 36621663 10 76 theme amino 1683:1687 arg1 residues 1694:1701 amino acid residues 45-52 1683:1707 amino acid residues 45-52 1683:1707 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 10 76 theme amino 1683:1687 arg1 sequence 1732:1739 the minimal peptide sequence 1712:1739 the minimal peptide sequence 1712:1739 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 1 77 theme recent 131:136 arg1 advances 138:145 recent advances 131:145 recent advances in cancer treatments 131:166 Despite recent advances in cancer treatments, pancreatic cancer has a dismal prognosis globally. 36621663 9 78 theme FXYD5 1439:1443 arg1 protein 1445:1451 The FXYD5 protein 1435:1451 The FXYD5 protein 1435:1451 The FXYD5 protein is overexpressed in various types of cancer and is modified by O-linked glycosylation. 36621663 10 79 theme detailed 1647:1654 arg1 mapping 1664:1670 detailed epitope mapping 1647:1670 detailed epitope mapping 1647:1670 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 10 80 theme protein 1578:1584 arg1 binding 1557:1563 the binding 1553:1563 the binding of the FXYD5 protein to mAb 12-13.8 1553:1599 We confirmed the binding of the FXYD5 protein to mAb 12-13.8 by using FXYD5-knockout MIA PaCa-2 cells, and detailed epitope mapping identified amino acid residues 45-52 as the minimal peptide sequence. 36621663 7 81 theme cancer 1271:1276 arg1 recurrence 1278:1287 the patients' cancer recurrence 1257:1287 the patients' cancer recurrence 1257:1287 Immunohistochemical staining of pancreatic and lung tumor tissues indicated that the increase of the staining strength by mAb 12-13.8 positively and inversely correlated with the patients' cancer recurrence and survival rate, respectively. 36621663 11 82 theme drug 1853:1856 arg1 delivery 1858:1865 drug delivery 1853:1865 drug delivery 1853:1865 Our results indicate that mAb 12-13.8 could be a valuable tool for FXYD5 studies, and useful in diagnostic and drug delivery applications for cancer patients. 36401641 6 0 theme due 958:960 arg1 variability 946:956 great molecular mass variability 925:956 great molecular mass variability due to the presence of N- and O-linked carbohydrates 925:1009 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 3 1 theme stem/progenitor 524:538 arg1 cells 540:544 hematopoietic stem/progenitor cells 510:544 hematopoietic stem/progenitor cells 510:544 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 6 2 theme mass 941:944 arg1 variability 946:956 great molecular mass variability 925:956 great molecular mass variability due to the presence of N- and O-linked carbohydrates 925:1009 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 8 3 theme detection 1416:1424 arg1 limits 1426:1431 detection limits 1416:1431 detection limits of 0.18 and 0.07 ng/ml 1416:1454 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 3 4 theme hematopoietic 510:522 arg1 cells 540:544 hematopoietic stem/progenitor cells 510:544 hematopoietic stem/progenitor cells 510:544 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 12 5 theme UT-7 2109:2112 arg1 cells 2114:2118 UT-7 cells 2109:2118 UT-7 cells 2109:2118 KEY POINTS: • Soluble glycosylated human SCF exerted improved proliferative activity on UT-7 cells. 36401641 6 6 theme great 925:929 arg1 variability 946:956 great molecular mass variability 925:956 great molecular mass variability due to the presence of N- and O-linked carbohydrates 925:1009 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 4 7 theme native-like 691:701 arg1 form 703:706 most native-like form 686:706 most native-like form 686:706 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 6 8 link bacteria-derived 1087:1102 arg1 hSCF 1104:1107 bacteria-derived hSCF 1087:1107 bacteria-derived hSCF 1087:1107 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 10 9 theme cytokine 1789:1796 arg1 staining 1798:1805 intracellular cytokine staining 1775:1805 intracellular cytokine staining 1775:1805 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 1 10 theme growth 164:169 arg1 factor 171:176 an early-acting growth factor 148:176 an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues 148:265 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 1 10 theme growth 164:169 arg1 factor 131:136 Human stem cell factor 115:136 Human stem cell factor (hSCF) 115:143 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 14 11 theme immunofluorescence 2267:2284 arg1 assays 2286:2291 immunofluorescence assays 2267:2291 immunofluorescence assays 2267:2291 • mAbs applications comprise sandwich ELISA, western blot, and immunofluorescence assays. 36401641 12 12 theme improved 2074:2081 arg1 activity 2097:2104 improved proliferative activity 2074:2104 improved proliferative activity 2074:2104 KEY POINTS: • Soluble glycosylated human SCF exerted improved proliferative activity on UT-7 cells. 36401641 6 13 theme carbohydrates 997:1009 arg1 presence 969:976 the presence 965:976 the presence of N- and O-linked carbohydrates 965:1009 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 4 14 theme recombinant 666:676 arg1 hSCF 678:681 recombinant hSCF 666:681 recombinant hSCF in most native-like form 666:706 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 11 15 theme glycosylated 1838:1849 arg1 expression 1857:1866 glycosylated rhSCF expression 1838:1866 glycosylated rhSCF expression 1838:1866 Our work shows that combining glycosylated rhSCF expression with hybridoma technology is a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses. 36401641 7 16 theme hybridoma 1116:1124 arg1 clones 1126:1131 Three hybridoma clones 1110:1131 Three hybridoma clones producing monoclonal antibodies (mAbs) with high specificity for the glycoprotein 1110:1213 Three hybridoma clones producing monoclonal antibodies (mAbs) with high specificity for the glycoprotein were obtained. 36401641 2 17 theme crucial 279:285 arg1 role 287:290 a crucial role 277:290 a crucial role 277:290 It plays a crucial role in hematopoiesis, gametogenesis, melanogenesis, intestinal motility, and in development and recovery of nervous and cardiovascular systems. 36401641 1 18 theme cell 126:129 arg1 factor 131:136 Human stem cell factor 115:136 Human stem cell factor (hSCF) 115:143 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 1 18 theme cell 126:129 arg1 factor 171:176 an early-acting growth factor 148:176 an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues 148:265 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 1 18 theme cell 126:129 arg1 hSCF 139:142 hSCF 139:142 hSCF 139:142 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 10 19 theme best 1673:1676 arg1 candidate 1678:1686 the best candidate 1669:1686 the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining 1669:1805 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 8 20 gly glycosylated 1288:1299 arg1 rhSCF 1301:1305 bacteria-derived and glycosylated rhSCF 1267:1305 bacteria-derived and glycosylated rhSCF 1267:1305 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 5 21 theme HEK293 882:887 arg1 cells 889:893 HEK293 cells 882:893 HEK293 cells 882:893 The soluble domain of hSCF was expressed in HEK293 cells. 36401641 12 22 theme glycosylated 2043:2054 arg1 SCF 2062:2064 • Soluble glycosylated human SCF 2033:2064 • Soluble glycosylated human SCF 2033:2064 KEY POINTS: • Soluble glycosylated human SCF exerted improved proliferative activity on UT-7 cells. 36401641 13 23 gly glycosylated 2166:2177 arg1 SCF 2185:2187 glycosylated human SCF 2166:2187 glycosylated human SCF 2166:2187 • Three mAbs with high specificity targeting glycosylated human SCF were obtained. 36401641 11 24 theme hybridoma 1873:1881 arg1 technology 1883:1892 hybridoma technology 1873:1892 hybridoma technology 1873:1892 Our work shows that combining glycosylated rhSCF expression with hybridoma technology is a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses. 36401641 3 25 theme gene 615:618 arg1 therapy 620:626 gene therapy 615:626 gene therapy 615:626 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 9 26 theme sugar 1547:1551 arg1 moieties 1553:1560 sugar moieties 1547:1560 sugar moieties 1547:1560 Interestingly, 1A10 mAb only recognized glycosylated rhSCF, suggesting that sugar moieties might be involved in epitope recognition. 36401641 9 27 gly glycosylated 1511:1522 arg1 rhSCF 1524:1528 glycosylated rhSCF 1511:1528 glycosylated rhSCF 1511:1528 Interestingly, 1A10 mAb only recognized glycosylated rhSCF, suggesting that sugar moieties might be involved in epitope recognition. 36401641 1 28 from migration 224:232 arg1 tissues 259:265 several tissues 251:265 several tissues 251:265 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 13 29 with mAbs 2129:2132 arg1 specificity 2144:2154 high specificity 2139:2154 high specificity targeting glycosylated human SCF 2139:2187 • Three mAbs with high specificity targeting glycosylated human SCF were obtained. 36401641 8 30 theme sandwich 1364:1371 arg1 assay 1379:1383 a sandwich ELISA assay 1362:1383 a sandwich ELISA assay for rhSCF quantification 1362:1408 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 5 31 theme hSCF 860:863 arg1 domain 850:855 The soluble domain 838:855 The soluble domain of hSCF 838:863 The soluble domain of hSCF was expressed in HEK293 cells. 36401641 5 31 theme hSCF 860:863 arg1 hSCF 860:863 hSCF 860:863 hSCF 860:863 The soluble domain of hSCF was expressed in HEK293 cells. 36401641 6 32 theme 2.5-fold 1031:1038 arg1 increase 1040:1047 a 2.5-fold increase 1029:1047 a 2.5-fold increase on proliferative activity 1029:1073 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 6 33 from increase 1040:1047 arg1 activity 1066:1073 proliferative activity 1052:1073 proliferative activity 1052:1073 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 0 34 theme human 91:95 arg1 factor 107:112 glycosylated human stem cell factor 78:112 glycosylated human stem cell factor 78:112 Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor. 36401641 13 35 theme human 2179:2183 arg1 SCF 2185:2187 glycosylated human SCF 2166:2187 glycosylated human SCF 2166:2187 • Three mAbs with high specificity targeting glycosylated human SCF were obtained. 36401641 10 36 theme rhSCF 1726:1730 arg1 glycoforms 1732:1741 the entire set rhSCF glycoforms 1711:1741 the entire set rhSCF glycoforms 1711:1741 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 9 37 theme epitope 1583:1589 arg1 recognition 1591:1601 epitope recognition 1583:1601 epitope recognition 1583:1601 Interestingly, 1A10 mAb only recognized glycosylated rhSCF, suggesting that sugar moieties might be involved in epitope recognition. 36401641 8 38 theme rhSCF 1389:1393 arg1 quantification 1395:1408 rhSCF quantification 1389:1408 rhSCF quantification 1389:1408 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 0 39 theme cell 102:105 arg1 factor 107:112 glycosylated human stem cell factor 78:112 glycosylated human stem cell factor 78:112 Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor. 36401641 12 40 theme KEY 2021:2023 arg1 POINTS 2025:2030 KEY POINTS 2021:2030 KEY POINTS: • Soluble glycosylated human SCF exerted improved proliferative activity on UT-7 cells. 2021:2119 KEY POINTS: • Soluble glycosylated human SCF exerted improved proliferative activity on UT-7 cells. 36401641 0 41 gly glycosylated 78:89 arg1 factor 107:112 glycosylated human stem cell factor 78:112 glycosylated human stem cell factor 78:112 Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor. 36401641 14 42 theme • 2204:2204 arg1 applications 2211:2222 • mAbs applications 2204:2222 • mAbs applications 2204:2222 • mAbs applications comprise sandwich ELISA, western blot, and immunofluorescence assays. 36401641 2 43 theme nervous 396:402 arg1 systems 423:429 nervous and cardiovascular systems 396:429 nervous and cardiovascular systems 396:429 It plays a crucial role in hematopoiesis, gametogenesis, melanogenesis, intestinal motility, and in development and recovery of nervous and cardiovascular systems. 36401641 13 44 theme high 2139:2142 arg1 specificity 2144:2154 high specificity 2139:2154 high specificity targeting glycosylated human SCF 2139:2187 • Three mAbs with high specificity targeting glycosylated human SCF were obtained. 36401641 11 45 dep obtain 1920:1925 arg1 improve 1976:1982 improve 1976:1982 improve glycoprotein-producing bioprocesses 1976:2018 Our work shows that combining glycosylated rhSCF expression with hybridoma technology is a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses. 36401641 4 46 theme in 767:768 arg1 functions 775:783 its in vivo functions 763:783 its in vivo functions 763:783 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 2 47 theme systems 423:429 arg1 development 368:378 development 368:378 development 368:378 It plays a crucial role in hematopoiesis, gametogenesis, melanogenesis, intestinal motility, and in development and recovery of nervous and cardiovascular systems. 36401641 2 47 theme systems 423:429 arg1 recovery 384:391 recovery 384:391 recovery 384:391 It plays a crucial role in hematopoiesis, gametogenesis, melanogenesis, intestinal motility, and in development and recovery of nervous and cardiovascular systems. 36401641 4 48 theme functions 775:783 arg1 complexity 749:758 the complexity 745:758 the complexity of its in vivo functions and for improving its biotechnological applications 745:835 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 10 49 theme glycoforms 1732:1741 arg1 immunodetection 1692:1706 immunodetection 1692:1706 immunodetection of the entire set rhSCF glycoforms in western blot assays 1692:1764 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 0 50 theme functional 15:24 arg1 evaluation 26:35 functional evaluation 15:35 functional evaluation 15:35 Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor. 36401641 10 51 theme intracellular 1775:1787 arg1 staining 1798:1805 intracellular cytokine staining 1775:1805 intracellular cytokine staining 1775:1805 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 6 52 theme purified 903:910 arg1 rhSCF 912:916 Highly purified rhSCF 896:916 Highly purified rhSCF 896:916 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 1 53 theme Human 115:119 arg1 factor 131:136 Human stem cell factor 115:136 Human stem cell factor (hSCF) 115:143 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 1 53 theme Human 115:119 arg1 factor 171:176 an early-acting growth factor 148:176 an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues 148:265 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 1 53 theme Human 115:119 arg1 hSCF 139:142 hSCF 139:142 hSCF 139:142 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 10 54 theme set 1722:1724 arg1 glycoforms 1732:1741 the entire set rhSCF glycoforms 1711:1741 the entire set rhSCF glycoforms 1711:1741 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 3 55 theme therapeutic 442:452 arg1 applications 454:465 Potential therapeutic applications 432:465 Potential therapeutic applications 432:465 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 1 56 theme early-acting 151:162 arg1 factor 171:176 an early-acting growth factor 148:176 an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues 148:265 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 1 56 theme early-acting 151:162 arg1 factor 131:136 Human stem cell factor 115:136 Human stem cell factor (hSCF) 115:143 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 10 57 from immunodetection 1692:1706 arg1 assays 1759:1764 western blot assays 1746:1764 western blot assays 1746:1764 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 0 58 theme monoclonal 46:55 arg1 antibodies 57:66 novel monoclonal antibodies 40:66 novel monoclonal antibodies 40:66 Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor. 36401641 11 59 theme specific 1927:1934 arg1 assays 1960:1965 specific suitable immunochemical assays 1927:1965 specific suitable immunochemical assays 1927:1965 Our work shows that combining glycosylated rhSCF expression with hybridoma technology is a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses. 36401641 10 60 theme western 1746:1752 arg1 blot 1754:1757 western blot 1746:1757 western blot assays 1746:1764 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 3 61 theme cells 540:544 arg1 mobilization 494:505 mobilization 494:505 mobilization of hematopoietic stem/progenitor cells to peripheral blood 494:564 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 3 61 theme cells 540:544 arg1 treatment 483:491 anemia treatment 476:491 anemia treatment 476:491 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 3 61 theme cells 540:544 arg1 efficiency 600:609 increasing gene transduction efficiency 571:609 increasing gene transduction efficiency for gene therapy 571:626 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 8 62 theme bacteria-derived 1267:1282 arg1 rhSCF 1301:1305 bacteria-derived and glycosylated rhSCF 1267:1305 bacteria-derived and glycosylated rhSCF 1267:1305 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 7 63 theme high 1177:1180 arg1 specificity 1182:1192 high specificity 1177:1192 high specificity for the glycoprotein 1177:1213 Three hybridoma clones producing monoclonal antibodies (mAbs) with high specificity for the glycoprotein were obtained. 36401641 2 64 theme intestinal 340:349 arg1 motility 351:358 intestinal motility 340:358 intestinal motility 340:358 It plays a crucial role in hematopoiesis, gametogenesis, melanogenesis, intestinal motility, and in development and recovery of nervous and cardiovascular systems. 36401641 2 64 theme intestinal 340:349 arg1 hematopoiesis 295:307 hematopoiesis 295:307 hematopoiesis 295:307 It plays a crucial role in hematopoiesis, gametogenesis, melanogenesis, intestinal motility, and in development and recovery of nervous and cardiovascular systems. 36401641 14 65 theme sandwich 2233:2240 arg1 ELISA 2242:2246 sandwich ELISA 2233:2246 sandwich ELISA 2233:2246 • mAbs applications comprise sandwich ELISA, western blot, and immunofluorescence assays. 36401641 10 66 theme binding 1632:1638 arg1 affinity 1640:1647 the highest binding affinity 1620:1647 the highest binding affinity 1620:1647 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 1 67 theme several 251:257 arg1 tissues 259:265 several tissues 251:265 several tissues 251:265 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 12 68 theme proliferative 2083:2095 arg1 activity 2097:2104 improved proliferative activity 2074:2104 improved proliferative activity 2074:2104 KEY POINTS: • Soluble glycosylated human SCF exerted improved proliferative activity on UT-7 cells. 36401641 6 69 theme molecular 931:939 arg1 variability 946:956 great molecular mass variability 925:956 great molecular mass variability due to the presence of N- and O-linked carbohydrates 925:1009 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 7 70 theme monoclonal 1143:1152 arg1 mAbs 1166:1169 mAbs 1166:1169 mAbs 1166:1169 Three hybridoma clones producing monoclonal antibodies (mAbs) with high specificity for the glycoprotein were obtained. 36401641 7 70 theme monoclonal 1143:1152 arg1 antibodies 1154:1163 monoclonal antibodies 1143:1163 monoclonal antibodies (mAbs) 1143:1170 Three hybridoma clones producing monoclonal antibodies (mAbs) with high specificity for the glycoprotein were obtained. 36401641 3 71 theme peripheral 549:558 arg1 blood 560:564 peripheral blood 549:564 peripheral blood 549:564 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 9 72 theme 1A10 1486:1489 arg1 mAb 1491:1493 1A10 mAb 1486:1493 1A10 mAb 1486:1493 Interestingly, 1A10 mAb only recognized glycosylated rhSCF, suggesting that sugar moieties might be involved in epitope recognition. 36401641 12 73 theme human 2056:2060 arg1 SCF 2062:2064 • Soluble glycosylated human SCF 2033:2064 • Soluble glycosylated human SCF 2033:2064 KEY POINTS: • Soluble glycosylated human SCF exerted improved proliferative activity on UT-7 cells. 36401641 4 74 theme most 686:689 arg1 form 703:706 most native-like form 686:706 most native-like form 686:706 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 3 75 theme transduction 587:598 arg1 efficiency 600:609 increasing gene transduction efficiency 571:609 increasing gene transduction efficiency for gene therapy 571:626 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 8 76 theme 1C4 1230:1232 arg1 mAbs 1242:1245 1C4 and 2D3 mAbs 1230:1245 1C4 and 2D3 mAbs 1230:1245 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 8 77 theme glycosylated 1288:1299 arg1 rhSCF 1301:1305 bacteria-derived and glycosylated rhSCF 1267:1305 bacteria-derived and glycosylated rhSCF 1267:1305 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 12 78 gly glycosylated 2043:2054 arg1 SCF 2062:2064 • Soluble glycosylated human SCF 2033:2064 • Soluble glycosylated human SCF 2033:2064 KEY POINTS: • Soluble glycosylated human SCF exerted improved proliferative activity on UT-7 cells. 36401641 3 79 theme increasing 571:580 arg1 efficiency 600:609 increasing gene transduction efficiency 571:609 increasing gene transduction efficiency for gene therapy 571:626 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 4 80 from hSCF 678:681 arg1 form 703:706 most native-like form 686:706 most native-like form 686:706 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 9 81 theme glycosylated 1511:1522 arg1 rhSCF 1524:1528 glycosylated rhSCF 1511:1528 glycosylated rhSCF 1511:1528 Interestingly, 1A10 mAb only recognized glycosylated rhSCF, suggesting that sugar moieties might be involved in epitope recognition. 36401641 8 82 theme 2D3 1238:1240 arg1 mAbs 1242:1245 1C4 and 2D3 mAbs 1230:1245 1C4 and 2D3 mAbs 1230:1245 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 6 83 theme O-linked 988:995 arg1 carbohydrates 997:1009 N- and O-linked carbohydrates 981:1009 N- and O-linked carbohydrates 981:1009 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 12 84 dep POINTS 2025:2030 arg1 exerted 2066:2072 exerted 2066:2072 exerted improved proliferative activity on UT-7 cells 2066:2118 KEY POINTS: • Soluble glycosylated human SCF exerted improved proliferative activity on UT-7 cells. 36401641 11 85 theme rhSCF 1851:1855 arg1 expression 1857:1866 glycosylated rhSCF expression 1838:1866 glycosylated rhSCF expression 1838:1866 Our work shows that combining glycosylated rhSCF expression with hybridoma technology is a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses. 36401641 1 86 from survival 239:246 arg1 tissues 259:265 several tissues 251:265 several tissues 251:265 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 10 87 gly glycoforms 1732:1741 arg1 set 1722:1724 the entire set rhSCF glycoforms 1711:1741 the entire set rhSCF glycoforms 1711:1741 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 10 87 gly glycoforms 1732:1741 arg1 rhSCF 1726:1730 the entire set rhSCF glycoforms 1711:1741 the entire set rhSCF glycoforms 1711:1741 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 6 88 link O-linked 988:995 arg1 carbohydrates 997:1009 N- and O-linked carbohydrates 981:1009 N- and O-linked carbohydrates 981:1009 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 6 89 theme N- 981:982 arg1 carbohydrates 997:1009 N- and O-linked carbohydrates 981:1009 N- and O-linked carbohydrates 981:1009 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 1 90 from differentiation 207:221 arg1 tissues 259:265 several tissues 251:265 several tissues 251:265 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 1 91 theme stem 121:124 arg1 factor 131:136 Human stem cell factor 115:136 Human stem cell factor (hSCF) 115:143 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 1 91 theme stem 121:124 arg1 factor 171:176 an early-acting growth factor 148:176 an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues 148:265 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 1 91 theme stem 121:124 arg1 hSCF 139:142 hSCF 139:142 hSCF 139:142 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 12 92 theme Soluble 2035:2041 arg1 SCF 2062:2064 • Soluble glycosylated human SCF 2033:2064 • Soluble glycosylated human SCF 2033:2064 KEY POINTS: • Soluble glycosylated human SCF exerted improved proliferative activity on UT-7 cells. 36401641 8 93 theme excellent 1330:1338 arg1 candidates 1340:1349 excellent candidates 1330:1349 excellent candidates 1330:1349 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 4 94 dep tools 644:648 arg1 characterize 653:664 characterize 653:664 to characterize recombinant hSCF in most native-like form 650:706 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 1 95 from proliferation 192:204 arg1 tissues 259:265 several tissues 251:265 several tissues 251:265 Human stem cell factor (hSCF) is an early-acting growth factor that promotes proliferation, differentiation, migration, and survival in several tissues. 36401641 4 96 dep in 767:768 arg1 vivo 770:773 vivo 770:773 vivo 770:773 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 6 97 theme proliferative 1052:1064 arg1 activity 1066:1073 proliferative activity 1052:1073 proliferative activity 1052:1073 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 11 98 theme powerful 1899:1906 arg1 strategy 1908:1915 a powerful strategy 1897:1915 a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses 1897:2018 Our work shows that combining glycosylated rhSCF expression with hybridoma technology is a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses. 36401641 0 99 theme glycosylated 78:89 arg1 factor 107:112 glycosylated human stem cell factor 78:112 glycosylated human stem cell factor 78:112 Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor. 36401641 0 100 theme stem 97:100 arg1 factor 107:112 glycosylated human stem cell factor 78:112 glycosylated human stem cell factor 78:112 Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor. 36401641 13 101 theme glycosylated 2166:2177 arg1 SCF 2185:2187 glycosylated human SCF 2166:2187 glycosylated human SCF 2166:2187 • Three mAbs with high specificity targeting glycosylated human SCF were obtained. 36401641 11 102 theme suitable 1936:1943 arg1 assays 1960:1965 specific suitable immunochemical assays 1927:1965 specific suitable immunochemical assays 1927:1965 Our work shows that combining glycosylated rhSCF expression with hybridoma technology is a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses. 36401641 8 103 theme ELISA 1373:1377 arg1 assay 1379:1383 a sandwich ELISA assay 1362:1383 a sandwich ELISA assay for rhSCF quantification 1362:1408 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 3 104 theme gene 582:585 arg1 efficiency 600:609 increasing gene transduction efficiency 571:609 increasing gene transduction efficiency for gene therapy 571:626 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 14 105 theme mAbs 2206:2209 arg1 applications 2211:2222 • mAbs applications 2204:2222 • mAbs applications 2204:2222 • mAbs applications comprise sandwich ELISA, western blot, and immunofluorescence assays. 36401641 4 106 theme improving 793:801 arg1 complexity 749:758 the complexity 745:758 the complexity of its in vivo functions and for improving its biotechnological applications 745:835 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 3 107 theme Potential 432:440 arg1 applications 454:465 Potential therapeutic applications 432:465 Potential therapeutic applications 432:465 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 5 108 theme soluble 842:848 arg1 domain 850:855 The soluble domain 838:855 The soluble domain of hSCF 838:863 The soluble domain of hSCF was expressed in HEK293 cells. 36401641 5 108 theme soluble 842:848 arg1 hSCF 860:863 hSCF 860:863 hSCF 860:863 The soluble domain of hSCF was expressed in HEK293 cells. 36401641 10 109 theme highest 1624:1630 arg1 affinity 1640:1647 the highest binding affinity 1620:1647 the highest binding affinity 1620:1647 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 11 110 theme immunochemical 1945:1958 arg1 assays 1960:1965 specific suitable immunochemical assays 1927:1965 specific suitable immunochemical assays 1927:1965 Our work shows that combining glycosylated rhSCF expression with hybridoma technology is a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses. 36401641 6 111 theme bacteria-derived 1087:1102 arg1 hSCF 1104:1107 bacteria-derived hSCF 1087:1107 bacteria-derived hSCF 1087:1107 Highly purified rhSCF showed great molecular mass variability due to the presence of N- and O-linked carbohydrates, and it presented a 2.5-fold increase on proliferative activity compared to bacteria-derived hSCF. 36401641 2 112 theme cardiovascular 408:421 arg1 systems 423:429 nervous and cardiovascular systems 396:429 nervous and cardiovascular systems 396:429 It plays a crucial role in hematopoiesis, gametogenesis, melanogenesis, intestinal motility, and in development and recovery of nervous and cardiovascular systems. 36401641 3 113 theme anemia 476:481 arg1 treatment 483:491 anemia treatment 476:491 anemia treatment 476:491 Potential therapeutic applications comprise anemia treatment, mobilization of hematopoietic stem/progenitor cells to peripheral blood, and increasing gene transduction efficiency for gene therapy. 36401641 0 114 theme novel 40:44 arg1 antibodies 57:66 novel monoclonal antibodies 40:66 novel monoclonal antibodies 40:66 Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor. 36401641 14 115 theme western 2249:2255 arg1 blot 2257:2260 western blot 2249:2260 western blot 2249:2260 • mAbs applications comprise sandwich ELISA, western blot, and immunofluorescence assays. 36401641 8 116 theme 0.18 1436:1439 arg1 limits 1426:1431 detection limits 1416:1431 detection limits of 0.18 and 0.07 ng/ml 1416:1454 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 10 117 theme entire 1715:1720 arg1 glycoforms 1732:1741 the entire set rhSCF glycoforms 1711:1741 the entire set rhSCF glycoforms 1711:1741 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 0 118 theme antibodies 57:66 arg1 Generation 0:9 Generation 0:9 Generation 0:9 Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor. 36401641 0 118 theme antibodies 57:66 arg1 evaluation 26:35 functional evaluation 15:35 functional evaluation 15:35 Generation and functional evaluation of novel monoclonal antibodies targeting glycosylated human stem cell factor. 36401641 8 119 link bacteria-derived 1267:1282 arg1 rhSCF 1301:1305 bacteria-derived and glycosylated rhSCF 1267:1305 bacteria-derived and glycosylated rhSCF 1267:1305 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 8 120 theme 0.07 ng/ml 1445:1454 arg1 limits 1426:1431 detection limits 1416:1431 detection limits of 0.18 and 0.07 ng/ml 1416:1454 1C4 and 2D3 mAbs were able to detect bacteria-derived and glycosylated rhSCF and demonstrated to be excellent candidates to develop a sandwich ELISA assay for rhSCF quantification, with detection limits of 0.18 and 0.07 ng/ml, respectively. 36401641 13 121 theme • 2121:2121 arg1 mAbs 2129:2132 • Three mAbs 2121:2132 • Three mAbs with high specificity targeting glycosylated human SCF 2121:2187 • Three mAbs with high specificity targeting glycosylated human SCF were obtained. 36401641 10 122 theme blot 1754:1757 arg1 assays 1759:1764 western blot assays 1746:1764 western blot assays 1746:1764 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 11 123 gly glycosylated 1838:1849 arg1 expression 1857:1866 glycosylated rhSCF expression 1838:1866 glycosylated rhSCF expression 1838:1866 Our work shows that combining glycosylated rhSCF expression with hybridoma technology is a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses. 36401641 4 124 theme new 640:642 arg1 tools 644:648 new tools 640:648 new tools to characterize recombinant hSCF in most native-like form 640:706 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 4 125 theme biotechnological 807:822 arg1 applications 824:835 its biotechnological applications 803:835 its biotechnological applications 803:835 Developing new tools to characterize recombinant hSCF in most native-like form as possible is crucial to understand the complexity of its in vivo functions and for improving its biotechnological applications. 36401641 11 126 theme glycoprotein-producing 1984:2005 arg1 bioprocesses 2007:2018 glycoprotein-producing bioprocesses 1984:2018 glycoprotein-producing bioprocesses 1984:2018 Our work shows that combining glycosylated rhSCF expression with hybridoma technology is a powerful strategy to obtain specific suitable immunochemical assays and thus improve glycoprotein-producing bioprocesses. 36401641 10 127 theme 1A10 1604:1607 arg1 mAb 1609:1611 1A10 mAb 1604:1611 1A10 mAb 1604:1611 1A10 mAb showed the highest binding affinity, and it constituted the best candidate for immunodetection of the entire set rhSCF glycoforms in western blot assays, and for intracellular cytokine staining. 36401641 7 128 gly glycoprotein 1202:1213 arg1 glycoprotein 1202:1213 the glycoprotein 1198:1213 the glycoprotein 1198:1213 Three hybridoma clones producing monoclonal antibodies (mAbs) with high specificity for the glycoprotein were obtained. 35897676 4 0 theme advanced 1014:1021 arg1 endometriosis 1023:1035 advanced endometriosis 1014:1035 advanced endometriosis 1014:1035 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 6 1 theme advanced 1482:1489 arg1 group 1505:1509 the advanced endometriosis group 1478:1509 the advanced endometriosis group 1478:1509 Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. 35897676 5 2 theme PHA-L-reactive 1184:1197 arg1 N-glycans 1215:1223 PHA-L-reactive multi-antennary N-glycans 1184:1223 PHA-L-reactive multi-antennary N-glycans 1184:1223 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 9 3 theme core 2131:2134 arg1 O-glycans 2143:2151 core 3 type O-glycans 2131:2151 core 3 type O-glycans 2131:2151 In the case of non-endometriosis patients, the observed differences were most probably caused by increased expression of core 3 type O-glycans. 35897676 4 4 with patients 1000:1007 arg1 those 1041:1045 those 1041:1045 those 1041:1045 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 4 4 with patients 1000:1007 arg1 endometriosis 1023:1035 advanced endometriosis 1014:1035 advanced endometriosis 1014:1035 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 5 5 theme N-glycans 1215:1223 arg1 expression 1170:1179 significantly higher expression 1149:1179 significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups 1149:1302 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 2 6 attach isolated 342:349 arg2 IgG 330:332 native serum IgG 317:332 native serum IgG 317:332 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 2 6 attach isolated 342:349 arg1 group 480:484 a control group 470:484 a control group of healthy women 470:501 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 2 6 attach isolated 342:349 arg1 women 497:501 healthy women 489:501 healthy women 489:501 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 2 6 attach isolated 342:349 arg1 sera 356:359 sera 356:359 sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases 356:458 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 4 7 theme control 1102:1108 arg1 group 1110:1114 the control group 1098:1114 the control group of healthy women 1098:1131 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 4 7 theme control 1102:1108 arg1 women 1127:1131 healthy women 1119:1131 healthy women 1119:1131 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 8 8 with women 1896:1900 arg1 patients 1934:1941 patients 1934:1941 patients with other gynecological diseases with an inflammatory background 1934:2007 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 8 8 with women 1896:1900 arg1 endometriosis 1916:1928 advanced endometriosis 1907:1928 advanced endometriosis 1907:1928 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 3 9 theme multi-antennary 692:706 arg1 N-glycans 708:716 multi-antennary N-glycans 692:716 multi-antennary N-glycans 692:716 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 5 10 from expression 1170:1179 arg1 IgG 1237:1239 isolated IgG 1228:1239 isolated IgG in the advanced endometriosis and the non-endometriosis groups 1228:1302 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 2 11 theme advanced 557:564 arg1 endometriosis 566:578 advanced endometriosis 557:578 advanced endometriosis 557:578 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 3 12 theme specific 745:752 arg1 lectins 737:743 lectins 737:743 lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) 737:827 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 2 13 theme native 317:322 arg1 IgG 330:332 native serum IgG 317:332 native serum IgG 317:332 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 7 14 theme N-glycans 1692:1700 arg1 O-glycosylation 1638:1652 isolated serum IgG O-glycosylation 1619:1652 isolated serum IgG O-glycosylation 1619:1652 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 7 14 theme N-glycans 1692:1700 arg1 expression 1662:1671 the expression 1658:1671 the expression of highly branched N-glycans 1658:1700 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 4 15 theme IgG 883:885 arg1 glycans 896:902 isolated serum IgG O-linked glycans 868:902 isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio 868:969 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 8 16 theme inflammatory 1985:1996 arg1 background 1998:2007 an inflammatory background 1982:2007 an inflammatory background 1982:2007 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 4 17 theme glycans 896:902 arg1 reactivities 852:863 The relative reactivities 839:863 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio 839:969 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 4 17 theme glycans 896:902 arg1 higher 990:995 higher 990:995 higher 990:995 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 0 18 from Development 83:93 arg1 Endometriosis 107:119 Advanced Endometriosis 98:119 Advanced Endometriosis 98:119 O-Glycosylation Changes in Serum Immunoglobulin G Are Associated with Inflammation Development in Advanced Endometriosis. 35897676 9 19 theme non-endometriosis 2025:2041 arg1 patients 2043:2050 non-endometriosis patients 2025:2050 non-endometriosis patients 2025:2050 In the case of non-endometriosis patients, the observed differences were most probably caused by increased expression of core 3 type O-glycans. 35897676 8 20 theme expression 1807:1816 arg1 helpful 1861:1867 helpful 1861:1867 helpful 1861:1867 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 8 20 theme expression 1807:1816 arg1 analysis 1791:1798 the analysis 1787:1798 the analysis of the expression of Jacalin-reactive i-IgG O-glycans 1787:1852 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 1 21 theme inflammatory 222:233 arg1 processes 235:243 inflammatory processes 222:243 inflammatory processes with an immune basis 222:264 Endometriosis is a gynecological disease, the pathogenesis of which seems to be directly related to inflammatory processes with an immune basis. 35897676 7 22 theme expression 1662:1671 arg1 analysis 1607:1614 the lectin-based analysis 1590:1614 the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans 1590:1700 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 2 23 theme endometriosis 566:578 arg1 differentiation 538:552 differentiation 538:552 differentiation of advanced endometriosis from the other two groups of women studied 538:621 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 7 24 with women 1723:1727 arg1 endometriosis 1743:1755 advanced endometriosis 1734:1755 advanced endometriosis 1734:1755 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 8 25 theme Jacalin-reactive 1821:1836 arg1 O-glycans 1844:1852 Jacalin-reactive i-IgG O-glycans 1821:1852 Jacalin-reactive i-IgG O-glycans 1821:1852 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 4 26 theme isolated 868:875 arg1 glycans 896:902 isolated serum IgG O-linked glycans 868:902 isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio 868:969 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 9 27 theme observed 2057:2064 arg1 differences 2066:2076 the observed differences 2053:2076 the observed differences 2053:2076 In the case of non-endometriosis patients, the observed differences were most probably caused by increased expression of core 3 type O-glycans. 35897676 5 28 theme non-endometriosis 1279:1295 arg1 groups 1297:1302 the non-endometriosis groups 1275:1302 the non-endometriosis groups 1275:1302 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 8 29 theme O-glycans 1844:1852 arg1 expression 1807:1816 the expression 1803:1816 the expression of Jacalin-reactive i-IgG O-glycans 1803:1852 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 1 30 theme disease 155:161 arg1 related 211:217 related 211:217 related 211:217 Endometriosis is a gynecological disease, the pathogenesis of which seems to be directly related to inflammatory processes with an immune basis. 35897676 1 30 theme disease 155:161 arg1 pathogenesis 168:179 the pathogenesis 164:179 the pathogenesis 164:179 Endometriosis is a gynecological disease, the pathogenesis of which seems to be directly related to inflammatory processes with an immune basis. 35897676 7 31 theme IgG 1634:1636 arg1 O-glycosylation 1638:1652 isolated serum IgG O-glycosylation 1619:1652 isolated serum IgG O-glycosylation 1619:1652 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 2 32 theme women 497:501 arg1 group 480:484 a control group 470:484 a control group of healthy women 470:501 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 2 32 theme women 497:501 arg1 women 497:501 healthy women 489:501 healthy women 489:501 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 4 33 theme women 1127:1131 arg1 group 1110:1114 the control group 1098:1114 the control group of healthy women 1098:1131 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 4 33 theme women 1127:1131 arg1 women 1127:1131 healthy women 1119:1131 healthy women 1119:1131 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 7 34 theme isolated 1619:1626 arg1 O-glycosylation 1638:1652 isolated serum IgG O-glycosylation 1619:1652 isolated serum IgG O-glycosylation 1619:1652 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 4 35 theme MPL/VVL 941:947 arg1 ratio 965:969 the MPL/VVL O-glycosylation ratio 937:969 isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio 868:969 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 5 36 theme advanced 1248:1255 arg1 endometriosis 1257:1269 the advanced endometriosis 1244:1269 the advanced endometriosis 1244:1269 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 6 37 theme Jacalin-reactive 1389:1404 arg1 O-glycans 1406:1414 Jacalin-reactive O-glycans 1389:1414 Jacalin-reactive O-glycans 1389:1414 Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. 35897676 7 38 theme healthy 1762:1768 arg1 women 1770:1774 healthy women 1762:1774 healthy women 1762:1774 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 4 39 theme specific 909:916 arg1 lectins 918:924 specific lectins 909:924 specific lectins 909:924 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 0 40 theme Advanced 98:105 arg1 Endometriosis 107:119 Advanced Endometriosis 98:119 Advanced Endometriosis 98:119 O-Glycosylation Changes in Serum Immunoglobulin G Are Associated with Inflammation Development in Advanced Endometriosis. 35897676 3 41 dep O-glycans 757:765 arg1 VVL 773:775 VVL 773:775 VVL 773:775 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 3 41 dep O-glycans 757:765 arg1 Jacalin 782:788 Jacalin 782:788 Jacalin 782:788 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 3 41 dep O-glycans 757:765 arg1 MPL 768:770 MPL 768:770 MPL 768:770 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 4 42 with glycans 896:902 arg1 lectins 918:924 specific lectins 909:924 specific lectins 909:924 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 4 43 theme ratio 965:969 arg1 reactivities 852:863 The relative reactivities 839:863 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio 839:969 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 4 43 theme ratio 965:969 arg1 higher 990:995 higher 990:995 higher 990:995 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 0 44 theme Inflammation 70:81 arg1 Development 83:93 Inflammation Development 70:93 Inflammation Development in Advanced Endometriosis 70:119 O-Glycosylation Changes in Serum Immunoglobulin G Are Associated with Inflammation Development in Advanced Endometriosis. 35897676 2 45 theme advanced 375:382 arg1 endometriosis 384:396 advanced endometriosis 375:396 advanced endometriosis 375:396 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 0 46 theme O-Glycosylation 0:14 arg1 Changes 16:22 O-Glycosylation Changes 0:22 O-Glycosylation Changes in Serum Immunoglobulin G 0:48 O-Glycosylation Changes in Serum Immunoglobulin G Are Associated with Inflammation Development in Advanced Endometriosis. 35897676 2 47 theme gynecological 437:449 arg1 diseases 451:458 benign gynecological diseases 430:458 benign gynecological diseases 430:458 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 9 48 theme type 2138:2141 arg1 O-glycans 2143:2151 core 3 type O-glycans 2131:2151 core 3 type O-glycans 2131:2151 In the case of non-endometriosis patients, the observed differences were most probably caused by increased expression of core 3 type O-glycans. 35897676 5 49 theme higher 1163:1168 arg1 expression 1170:1179 significantly higher expression 1149:1179 significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups 1149:1302 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 2 50 theme control 472:478 arg1 group 480:484 a control group 470:484 a control group of healthy women 470:501 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 2 50 theme control 472:478 arg1 women 497:501 healthy women 489:501 healthy women 489:501 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 5 51 theme control 1325:1331 arg1 group 1333:1337 the control group 1321:1337 the control group 1321:1337 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 0 52 theme Immunoglobulin 33:46 arg1 G 48:48 Serum Immunoglobulin G 27:48 Serum Immunoglobulin G 27:48 O-Glycosylation Changes in Serum Immunoglobulin G Are Associated with Inflammation Development in Advanced Endometriosis. 35897676 7 53 theme cluster 1545:1551 arg1 analysis 1553:1560 cluster analysis 1545:1560 cluster analysis 1545:1560 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 6 54 located observed 1436:1443 arg1 non-endometriosis 1452:1468 the non-endometriosis 1448:1468 the non-endometriosis 1448:1468 Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. 35897676 6 54 located observed 1436:1443 arg1 group 1505:1509 the advanced endometriosis group 1478:1509 the advanced endometriosis group 1478:1509 Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. 35897676 6 54 located observed 1436:1443 arg2 expression 1375:1384 significantly higher expression 1354:1384 significantly higher expression of Jacalin-reactive O-glycans in isolated IgG 1354:1430 Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. 35897676 2 55 from groups 599:604 arg1 differentiation 538:552 differentiation 538:552 differentiation of advanced endometriosis from the other two groups of women studied 538:621 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 7 56 theme curve 1535:1539 arg1 results 1516:1522 The results 1512:1522 The results of the ROC curve and cluster analysis 1512:1560 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 8 57 theme gynecological 1954:1966 arg1 diseases 1968:1975 other gynecological diseases 1948:1975 other gynecological diseases 1948:1975 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 5 58 dep group 1333:1337 arg1 comparison 1307:1316 comparison 1307:1316 comparison 1307:1316 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 4 59 theme other 1052:1056 arg1 diseases 1072:1079 other gynecological diseases 1052:1079 other gynecological diseases 1052:1079 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 3 60 theme O-glycosylation 654:668 arg1 expression 678:687 the expression 674:687 the expression of multi-antennary N-glycans 674:716 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 3 60 theme O-glycosylation 654:668 arg1 analysis 632:639 the analysis 628:639 the analysis of serum IgG O-glycosylation 628:668 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 2 61 with women 364:368 arg1 endometriosis 384:396 advanced endometriosis 375:396 advanced endometriosis 375:396 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 2 61 with women 364:368 arg1 diseases 451:458 benign gynecological diseases 430:458 benign gynecological diseases 430:458 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 3 62 theme serum 644:648 arg1 O-glycosylation 654:668 serum IgG O-glycosylation 644:668 serum IgG O-glycosylation 644:668 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 2 63 theme women 364:368 arg1 sera 356:359 sera 356:359 sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases 356:458 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 3 64 with lectin-ELISA 719:730 arg1 lectins 737:743 lectins 737:743 lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) 737:827 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 1 65 with processes 235:243 arg1 basis 260:264 an immune basis 250:264 an immune basis 250:264 Endometriosis is a gynecological disease, the pathogenesis of which seems to be directly related to inflammatory processes with an immune basis. 35897676 2 66 gly O-glycosylation 298:312 arg1 IgG 338:340 IgG 338:340 IgG 338:340 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 2 66 gly O-glycosylation 298:312 arg1 IgG 330:332 native serum IgG 317:332 native serum IgG 317:332 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 2 66 gly O-glycosylation 298:312 arg1 context 511:517 the context 507:517 the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied 507:621 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 6 67 theme endometriosis 1491:1503 arg1 group 1505:1509 the advanced endometriosis group 1478:1509 the advanced endometriosis group 1478:1509 Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. 35897676 2 68 theme other 589:593 arg1 women 609:613 women 609:613 women studied 609:621 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 2 68 theme other 589:593 arg1 groups 599:604 the other two groups 585:604 the other two groups of women studied 585:621 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 8 69 with endometriosis 1916:1928 arg1 diseases 1968:1975 other gynecological diseases 1948:1975 other gynecological diseases 1948:1975 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 8 69 with endometriosis 1916:1928 arg1 background 1998:2007 an inflammatory background 1982:2007 an inflammatory background 1982:2007 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 8 70 theme other 1948:1952 arg1 diseases 1968:1975 other gynecological diseases 1948:1975 other gynecological diseases 1948:1975 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 5 71 theme multi-antennary 1199:1213 arg1 N-glycans 1215:1223 PHA-L-reactive multi-antennary N-glycans 1184:1223 PHA-L-reactive multi-antennary N-glycans 1184:1223 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 2 72 theme women 609:613 arg1 women 609:613 women 609:613 women studied 609:621 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 2 72 theme women 609:613 arg1 groups 599:604 the other two groups 585:604 the other two groups of women studied 585:621 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 4 73 theme healthy 1119:1125 arg1 women 1127:1131 healthy women 1119:1131 healthy women 1119:1131 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 3 74 theme N-glycans 708:716 arg1 expression 678:687 the expression 674:687 the expression of multi-antennary N-glycans 674:716 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 3 74 theme N-glycans 708:716 arg1 analysis 632:639 the analysis 628:639 the analysis of serum IgG O-glycosylation 628:668 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 2 75 theme serum 324:328 arg1 IgG 330:332 native serum IgG 317:332 native serum IgG 317:332 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 7 76 theme branched 1683:1690 arg1 N-glycans 1692:1700 highly branched N-glycans 1676:1700 highly branched N-glycans 1676:1700 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 4 77 with ratio 965:969 arg1 lectins 918:924 specific lectins 909:924 specific lectins 909:924 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 4 78 theme serum 877:881 arg1 IgG 883:885 serum IgG 877:885 isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio 868:969 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 4 79 theme O-linked 887:894 arg1 glycans 896:902 isolated serum IgG O-linked glycans 868:902 isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio 868:969 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 9 80 theme patients 2043:2050 arg1 case 2017:2020 the case 2013:2020 the case of non-endometriosis patients 2013:2050 In the case of non-endometriosis patients, the observed differences were most probably caused by increased expression of core 3 type O-glycans. 35897676 5 81 from IgG 1237:1239 arg1 endometriosis 1257:1269 the advanced endometriosis 1244:1269 the advanced endometriosis 1244:1269 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 5 81 from IgG 1237:1239 arg1 groups 1297:1302 the non-endometriosis groups 1275:1302 the non-endometriosis groups 1275:1302 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 7 82 theme O-glycosylation 1638:1652 arg1 analysis 1607:1614 the lectin-based analysis 1590:1614 the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans 1590:1700 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 4 83 theme relative 843:850 arg1 reactivities 852:863 The relative reactivities 839:863 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio 839:969 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 4 83 theme relative 843:850 arg1 higher 990:995 higher 990:995 higher 990:995 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 8 84 from differentiation 1872:1886 arg1 helpful 1861:1867 helpful 1861:1867 helpful 1861:1867 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 8 84 from differentiation 1872:1886 arg1 analysis 1791:1798 the analysis 1787:1798 the analysis of the expression of Jacalin-reactive i-IgG O-glycans 1787:1852 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 1 85 theme gynecological 141:153 arg1 disease 155:161 a gynecological disease 139:161 a gynecological disease 139:161 Endometriosis is a gynecological disease, the pathogenesis of which seems to be directly related to inflammatory processes with an immune basis. 35897676 1 85 theme gynecological 141:153 arg1 Endometriosis 122:134 Endometriosis 122:134 Endometriosis 122:134 Endometriosis is a gynecological disease, the pathogenesis of which seems to be directly related to inflammatory processes with an immune basis. 35897676 7 86 theme serum 1628:1632 arg1 O-glycosylation 1638:1652 isolated serum IgG O-glycosylation 1619:1652 isolated serum IgG O-glycosylation 1619:1652 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 3 87 used used 833:836 arg2 lectin-ELISA 719:730 lectin-ELISA 719:730 lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) 719:827 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 8 88 from helpful 1861:1867 arg1 differentiation 1872:1886 differentiation 1872:1886 differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background 1872:2007 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 6 89 theme isolated 1419:1426 arg1 IgG 1428:1430 isolated IgG 1419:1430 isolated IgG 1419:1430 Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. 35897676 8 90 theme i-IgG 1838:1842 arg1 O-glycans 1844:1852 Jacalin-reactive i-IgG O-glycans 1821:1852 Jacalin-reactive i-IgG O-glycans 1821:1852 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 2 91 theme healthy 489:495 arg1 women 497:501 healthy women 489:501 healthy women 489:501 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 6 92 theme O-glycans 1406:1414 arg1 expression 1375:1384 significantly higher expression 1354:1384 significantly higher expression of Jacalin-reactive O-glycans in isolated IgG 1354:1430 Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. 35897676 7 93 theme lectin-based 1594:1605 arg1 analysis 1607:1614 the lectin-based analysis 1590:1614 the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans 1590:1700 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 2 94 theme utility 526:532 arg1 context 511:517 the context 507:517 the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied 507:621 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 0 95 from Changes 16:22 arg1 G 48:48 Serum Immunoglobulin G 27:48 Serum Immunoglobulin G 27:48 O-Glycosylation Changes in Serum Immunoglobulin G Are Associated with Inflammation Development in Advanced Endometriosis. 35897676 3 96 theme branched 802:809 arg1 PHA-L 822:826 PHA-L 822:826 PHA-L 822:826 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 3 96 theme branched 802:809 arg1 N-glycans 811:819 highly branched N-glycans 795:819 highly branched N-glycans (PHA-L) 795:827 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 9 97 theme increased 2107:2115 arg1 expression 2117:2126 increased expression 2107:2126 increased expression of core 3 type O-glycans 2107:2151 In the case of non-endometriosis patients, the observed differences were most probably caused by increased expression of core 3 type O-glycans. 35897676 6 98 theme higher 1368:1373 arg1 expression 1375:1384 significantly higher expression 1354:1384 significantly higher expression of Jacalin-reactive O-glycans in isolated IgG 1354:1430 Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. 35897676 8 99 with patients 1934:1941 arg1 diseases 1968:1975 other gynecological diseases 1948:1975 other gynecological diseases 1948:1975 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 8 99 with patients 1934:1941 arg1 background 1998:2007 an inflammatory background 1982:2007 an inflammatory background 1982:2007 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 6 100 from expression 1375:1384 arg1 IgG 1428:1430 isolated IgG 1419:1430 isolated IgG 1419:1430 Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. 35897676 7 101 theme advanced 1734:1741 arg1 endometriosis 1743:1755 advanced endometriosis 1734:1755 advanced endometriosis 1734:1755 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 0 102 theme Serum 27:31 arg1 G 48:48 Serum Immunoglobulin G 27:48 Serum Immunoglobulin G 27:48 O-Glycosylation Changes in Serum Immunoglobulin G Are Associated with Inflammation Development in Advanced Endometriosis. 35897676 8 103 theme advanced 1907:1914 arg1 endometriosis 1916:1928 advanced endometriosis 1907:1928 advanced endometriosis 1907:1928 Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. 35897676 2 104 theme benign 430:435 arg1 diseases 451:458 benign gynecological diseases 430:458 benign gynecological diseases 430:458 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 9 105 theme O-glycans 2143:2151 arg1 expression 2117:2126 increased expression 2107:2126 increased expression of core 3 type O-glycans 2107:2151 In the case of non-endometriosis patients, the observed differences were most probably caused by increased expression of core 3 type O-glycans. 35897676 4 106 theme O-glycosylation 949:963 arg1 ratio 965:969 the MPL/VVL O-glycosylation ratio 937:969 isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio 868:969 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 7 107 theme analysis 1553:1560 arg1 results 1516:1522 The results 1512:1522 The results of the ROC curve and cluster analysis 1512:1560 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 3 108 theme IgG 650:652 arg1 O-glycosylation 654:668 serum IgG O-glycosylation 644:668 serum IgG O-glycosylation 644:668 For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. 35897676 2 109 theme IgG 338:340 arg1 O-glycosylation 298:312 the O-glycosylation 294:312 the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women 294:501 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 7 110 gly O-glycosylation 1638:1652 arg1 N-glycans 1692:1700 highly branched N-glycans 1676:1700 highly branched N-glycans 1676:1700 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 2 111 theme IgG 330:332 arg1 O-glycosylation 298:312 the O-glycosylation 294:312 the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women 294:501 Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. 35897676 5 112 theme isolated 1228:1235 arg1 IgG 1237:1239 isolated IgG 1228:1239 isolated IgG in the advanced endometriosis and the non-endometriosis groups 1228:1302 We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. 35897676 7 113 theme ROC 1531:1533 arg1 curve 1535:1539 the ROC curve 1527:1539 the ROC curve 1527:1539 The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. 35897676 4 114 theme gynecological 1058:1070 arg1 diseases 1072:1079 other gynecological diseases 1052:1079 other gynecological diseases 1052:1079 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 4 115 link O-linked 887:894 arg1 glycans 896:902 isolated serum IgG O-linked glycans 868:902 isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio 868:969 The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. 35897676 1 116 theme immune 253:258 arg1 basis 260:264 an immune basis 250:264 an immune basis 250:264 Endometriosis is a gynecological disease, the pathogenesis of which seems to be directly related to inflammatory processes with an immune basis. 35676258 0 0 theme bi-domain 63:71 arg1 exostosins 73:82 bi-domain exostosins 63:82 bi-domain exostosins 63:82 The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis. 35676258 6 1 theme backbone 1038:1045 arg1 extension 1047:1055 backbone extension 1038:1055 backbone extension 1038:1055 We explain the ineffectiveness of EXTL3's GT47 domain to transfer β-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. 35676258 1 2 theme modified 142:149 arg1 sulfate 122:128 Heparan sulfate 114:128 Heparan sulfate 114:128 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 1 2 theme modified 142:149 arg1 glycan 160:165 a highly modified O-linked glycan 133:165 a highly modified O-linked glycan that performs diverse physiological roles in animal tissues 133:225 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 0 3 theme exostosins 73:82 arg1 roles 54:58 the different roles 40:58 the different roles of bi-domain exostosins in heparan sulfate synthesis 40:111 The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis. 35676258 0 4 theme sulfate 95:101 arg1 synthesis 103:111 heparan sulfate synthesis 87:111 heparan sulfate synthesis 87:111 The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis. 35676258 3 5 theme monosaccharide 499:512 arg1 unit 514:517 monosaccharide unit 499:517 monosaccharide unit 499:517 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 1 6 theme O-linked 151:158 arg1 sulfate 122:128 Heparan sulfate 114:128 Heparan sulfate 114:128 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 1 6 theme O-linked 151:158 arg1 glycan 160:165 a highly modified O-linked glycan 133:165 a highly modified O-linked glycan that performs diverse physiological roles in animal tissues 133:225 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 0 7 theme heparan 87:93 arg1 sulfate 95:101 heparan sulfate 87:101 heparan sulfate synthesis 87:111 The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis. 35676258 5 8 from structure 775:783 arg1 forms 840:844 apo and UDP-bound forms 822:844 apo and UDP-bound forms 822:844 Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. 35676258 3 9 dep domains 443:449 arg1 domains 443:449 two glycosyltransferase domains 419:449 two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone 419:533 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 3 9 dep domains 443:449 arg1 -each 466:470 -each 466:470 two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone 419:533 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 3 9 dep domains 443:449 arg1 GT64 461:464 GT64 461:464 GT64 461:464 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 3 9 dep domains 443:449 arg1 GT47 452:455 GT47 452:455 GT47 452:455 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 7 10 theme heparan 1084:1090 arg1 polymerisation 1109:1122 heparan sulfate backbone polymerisation 1084:1122 heparan sulfate backbone polymerisation 1084:1122 We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism. 35676258 2 11 dep quickly 235:241 arg1 modified 243:250 modified 243:250 modified 243:250 Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. 35676258 1 12 link O-linked 151:158 arg1 sulfate 122:128 Heparan sulfate 114:128 Heparan sulfate 114:128 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 1 12 link O-linked 151:158 arg1 glycan 160:165 a highly modified O-linked glycan 133:165 a highly modified O-linked glycan that performs diverse physiological roles in animal tissues 133:225 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 2 13 theme alternating 304:314 arg1 residues 363:370 alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues 304:370 alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues 304:370 Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. 35676258 7 14 theme simple 1136:1141 arg1 mechanism 1156:1164 a simple dissociative mechanism 1134:1164 a simple dissociative mechanism 1134:1164 We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism. 35676258 4 15 theme exostosin-like 575:588 arg1 structures 554:563 previous structures 545:563 previous structures of murine exostosin-like 2 (EXTL2) 545:598 Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. 35676258 4 16 theme architecture 664:675 arg1 rest 642:645 the rest 638:645 the rest of the bi-domain architecture 638:675 Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. 35676258 0 17 theme EXTL3 17:21 arg1 structure 4:12 The structure 0:12 The structure of EXTL3 0:21 The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis. 35676258 4 18 theme murine 568:573 arg1 exostosin-like 575:588 murine exostosin-like 2 568:590 murine exostosin-like 2 (EXTL2) 568:598 Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. 35676258 4 18 theme murine 568:573 arg1 EXTL2 593:597 EXTL2 593:597 EXTL2 593:597 Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. 35676258 3 19 contain possess 411:417 arg2 GT47 452:455 GT47 452:455 GT47 452:455 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 3 19 contain possess 411:417 arg1 enzymes 393:399 These enzymes 387:399 These enzymes 387:399 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 3 19 contain possess 411:417 arg2 domains 443:449 two glycosyltransferase domains 419:449 two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone 419:533 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 3 19 contain possess 411:417 arg2 GT64 461:464 GT64 461:464 GT64 461:464 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 6 20 theme processive 1014:1023 arg1 mechanism 1025:1033 a processive mechanism 1012:1033 a processive mechanism of backbone extension 1012:1055 We explain the ineffectiveness of EXTL3's GT47 domain to transfer β-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. 35676258 1 21 theme diverse 181:187 arg1 roles 203:207 diverse physiological roles 181:207 diverse physiological roles 181:207 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 5 22 theme exostosin-like 794:807 arg1 structure 775:783 the structure 771:783 the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms 771:844 Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. 35676258 6 23 theme β-D-glucuronosyl 913:928 arg1 units 930:934 β-D-glucuronosyl units 913:934 β-D-glucuronosyl units 913:934 We explain the ineffectiveness of EXTL3's GT47 domain to transfer β-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. 35676258 7 24 theme backbone 1100:1107 arg1 polymerisation 1109:1122 heparan sulfate backbone polymerisation 1084:1122 heparan sulfate backbone polymerisation 1084:1122 We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism. 35676258 3 25 theme unit 514:517 arg1 type 491:494 one type 487:494 one type of monosaccharide unit 487:517 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 5 26 theme UDP-bound 830:838 arg1 forms 840:844 apo and UDP-bound forms 822:844 apo and UDP-bound forms 822:844 Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. 35676258 6 27 theme bi-domain 974:982 arg1 architecture 984:995 the bi-domain architecture 970:995 the bi-domain architecture 970:995 We explain the ineffectiveness of EXTL3's GT47 domain to transfer β-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. 35676258 4 28 theme bi-domain 654:662 arg1 architecture 664:675 the bi-domain architecture 650:675 the bi-domain architecture 650:675 Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. 35676258 4 29 theme previous 545:552 arg1 structures 554:563 previous structures 545:563 previous structures of murine exostosin-like 2 (EXTL2) 545:598 Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. 35676258 0 30 from roles 54:58 arg1 synthesis 103:111 heparan sulfate synthesis 87:111 heparan sulfate synthesis 87:111 The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis. 35676258 5 31 theme human 788:792 arg1 EXTL3 812:816 EXTL3 812:816 EXTL3 812:816 Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. 35676258 5 31 theme human 788:792 arg1 exostosin-like 794:807 human exostosin-like 3 788:809 human exostosin-like 3 (EXTL3) 788:817 Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. 35676258 3 32 theme glycosyltransferase 423:441 arg1 domains 443:449 two glycosyltransferase domains 419:449 two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone 419:533 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 3 32 theme glycosyltransferase 423:441 arg1 GT64 461:464 GT64 461:464 GT64 461:464 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 3 32 theme glycosyltransferase 423:441 arg1 GT47 452:455 GT47 452:455 GT47 452:455 These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. 35676258 6 33 theme domain 894:899 arg1 ineffectiveness 862:876 the ineffectiveness 858:876 the ineffectiveness of EXTL3's GT47 domain to transfer β-D-glucuronosyl units 858:934 We explain the ineffectiveness of EXTL3's GT47 domain to transfer β-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. 35676258 2 34 theme residues 363:370 arg1 polysaccharide 286:299 a polysaccharide 284:299 a polysaccharide of alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues 284:370 Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. 35676258 2 34 theme residues 363:370 arg1 it 253:254 it 253:254 it 253:254 Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. 35676258 7 35 theme sulfate 1092:1098 arg1 polymerisation 1109:1122 heparan sulfate backbone polymerisation 1084:1122 heparan sulfate backbone polymerisation 1084:1122 We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism. 35676258 6 36 theme GT47 889:892 arg1 domain 894:899 EXTL3's GT47 domain 881:899 EXTL3's GT47 domain 881:899 We explain the ineffectiveness of EXTL3's GT47 domain to transfer β-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. 35676258 2 37 theme N-acetyl-α-D-glucosaminyl 337:361 arg1 residues 363:370 alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues 304:370 alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues 304:370 Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. 35676258 4 38 dep is 677:678 arg1 co-operate 732:741 co-operate 732:741 co-operate is unknown 732:752 Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. 35676258 1 39 theme Heparan 114:120 arg1 sulfate 122:128 Heparan sulfate 114:128 Heparan sulfate 114:128 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 1 39 theme Heparan 114:120 arg1 glycan 160:165 a highly modified O-linked glycan 133:165 a highly modified O-linked glycan that performs diverse physiological roles in animal tissues 133:225 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 1 40 theme animal 212:217 arg1 tissues 219:225 animal tissues 212:225 animal tissues 212:225 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 2 41 theme β-D-glucuronosyl 316:331 arg1 residues 363:370 alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues 304:370 alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues 304:370 Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. 35676258 1 42 dep diverse 181:187 arg1 physiological 189:201 physiological 189:201 physiological 189:201 Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. 35676258 5 43 theme apo 822:824 arg1 forms 840:844 apo and UDP-bound forms 822:844 apo and UDP-bound forms 822:844 Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. 35676258 0 44 theme different 44:52 arg1 roles 54:58 the different roles 40:58 the different roles of bi-domain exostosins in heparan sulfate synthesis 40:111 The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis. 35676258 7 45 theme dissociative 1143:1154 arg1 mechanism 1156:1164 a simple dissociative mechanism 1134:1164 a simple dissociative mechanism 1134:1164 We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism. 35676258 6 46 theme extension 1047:1055 arg1 mechanism 1025:1033 a processive mechanism 1012:1033 a processive mechanism of backbone extension 1012:1055 We explain the ineffectiveness of EXTL3's GT47 domain to transfer β-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. 35676258 4 47 theme GT64 625:628 arg1 domain 630:635 the GT64 domain 621:635 the GT64 domain 621:635 Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. 36916376 3 0 theme Akt 1024:1026 arg1 LPS 1066:1068 si-Akt+2 000 mg/L LPS 1048:1068 si-Akt+2 000 mg/L LPS 1048:1068 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 0 theme Akt 1024:1026 arg1 group 1041:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group 986:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS) 986:1069 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 1 theme endothelial 2464:2474 arg1 cells 2476:2480 the endothelial cells 2460:2480 the endothelial cells of the OGT-OE+LPS group 2460:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 3 2 theme mg/L 890:893 arg1 LPS 895:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 2 theme mg/L 890:893 arg1 group 860:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group 809:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS) 809:898 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 3 from p38MAPK 2427:2433 arg1 cells 2476:2480 the endothelial cells 2460:2480 the endothelial cells of the OGT-OE+LPS group 2460:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 6 4 theme inflammatory 1954:1965 arg1 cytokines 1967:1975 inflammatory cytokines 1954:1975 inflammatory cytokines 1954:1975 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 7 5 theme ICAM-1 2686:2691 arg1 mRNA 2693:2696 ICAM-1 mRNA 2686:2696 ICAM-1 mRNA (2-ΔΔCt) 2686:2705 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 5 theme ICAM-1 2686:2691 arg1 2-ΔΔCt 2699:2704 2-ΔΔCt 2699:2704 2-ΔΔCt 2699:2704 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 4 6 theme chain 1174:1178 arg1 reaction 1180:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction 1105:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) 1105:1197 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 6 theme chain 1174:1178 arg1 RT-qPCR 1190:1196 RT-qPCR 1190:1196 RT-qPCR 1190:1196 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 10 7 theme ICAM-1 3453:3458 arg1 2-ΔΔCt 3466:3471 2-ΔΔCt 3466:3471 2-ΔΔCt 3466:3471 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 7 theme ICAM-1 3453:3458 arg1 mRNA 3460:3463 ICAM-1 mRNA 3453:3463 ICAM-1 mRNA (2-ΔΔCt) 3453:3472 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 3 8 theme mg/L 542:545 arg1 LPS 547:549 2 000 mg/L LPS 536:549 2 000 mg/L LPS 536:549 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 8 theme mg/L 542:545 arg1 group 529:533 LPS group 525:533 LPS group (2 000 mg/L LPS) 525:550 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 1 9 theme signaling 296:304 arg1 pathway 306:312 the inflammatory signaling pathway 279:312 the inflammatory signaling pathway of endothelial cells 279:333 OBJECTIVE To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells. 36916376 3 10 theme +LPS 1036:1039 arg1 LPS 1066:1068 si-Akt+2 000 mg/L LPS 1048:1068 si-Akt+2 000 mg/L LPS 1048:1068 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 10 theme +LPS 1036:1039 arg1 group 1041:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group 986:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS) 986:1069 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 11 theme serine/threonine 901:916 arg1 LPS 977:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 11 theme serine/threonine 901:916 arg1 group 945:949 serine/threonine kinase (Akt) inhibitor+LPS group 901:949 serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) 901:980 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 12 12 theme modification 4130:4141 arg1 level 4112:4116 The decreased level 4098:4116 The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors 4098:4339 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 8 13 theme blank 2966:2970 arg1 group 2980:2984 the blank control group 2962:2984 the blank control group 2962:2984 Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. 36916376 2 14 used used 458:461 arg2 cells 419:423 cells 419:423 cells in logarithmic growth phase 419:451 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 9 15 theme inhibitor 3173:3181 arg1 pretreatment 3153:3164 pretreatment 3153:3164 pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor 3153:3231 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 6 16 theme signaling 2292:2300 arg1 pathways 2302:2309 inflammatory signaling pathways 2279:2309 inflammatory signaling pathways 2279:2309 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 7 17 theme p65 2442:2444 arg1 expressions 2392:2402 the expressions 2388:2402 the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group 2388:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 6 18 from modification 1787:1798 arg1 group 1823:1827 the LPS group 1815:1827 the LPS group 1815:1827 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 4 19 used used 1203:1206 arg2 RT-qPCR 1190:1196 RT-qPCR 1190:1196 RT-qPCR 1190:1196 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 19 used used 1203:1206 arg2 reaction 1180:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction 1105:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) 1105:1197 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 7 20 theme signal 2906:2911 arg1 pathway 2913:2919 the endothelial inflammatory signal pathway 2877:2919 the endothelial inflammatory signal pathway under the LPS stimulation 2877:2945 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 2 21 theme Human 344:348 arg1 cells 377:381 Human umbilical vein endothelial cells 344:381 METHODS Human umbilical vein endothelial cells (HUVEC) 336:389 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 2 21 theme Human 344:348 arg1 HUVEC 384:388 HUVEC 384:388 HUVEC 384:388 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 9 22 theme RhoA 3184:3187 arg1 inhibitor 3189:3197 RhoA inhibitor 3184:3197 RhoA inhibitor 3184:3197 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 3 23 theme 000 1057:1059 arg1 LPS 1066:1068 si-Akt+2 000 mg/L LPS 1048:1068 si-Akt+2 000 mg/L LPS 1048:1068 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 23 theme 000 1057:1059 arg1 group 1041:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group 986:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS) 986:1069 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 11 24 theme VCAM-1 3906:3911 arg1 mRNA 3866:3869 ICAM-1 mRNA 3859:3869 ICAM-1 mRNA (2-ΔΔCt) 3859:3878 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 24 theme VCAM-1 3906:3911 arg1 2-ΔΔCt 3919:3924 2-ΔΔCt 3919:3924 2-ΔΔCt 3919:3924 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 24 theme VCAM-1 3906:3911 arg1 mRNA 3913:3916 VCAM-1 mRNA 3906:3916 VCAM-1 mRNA (2-ΔΔCt) 3906:3925 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 12 25 theme decreased 4102:4110 arg1 level 4112:4116 The decreased level 4098:4116 The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors 4098:4339 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 12 26 theme pathways 4238:4245 arg1 activation 4201:4210 partial activation 4193:4210 partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, 4193:4288 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 4 27 theme cytokines 1259:1267 arg1 levels 1236:1241 the transcription levels 1218:1241 the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)] 1218:1414 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 6 28 dep increased 2001:2009 arg1 1.03±0.29 2046:2054 1.03±0.29 2046:2054 1.03±0.29 2046:2054 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 28 dep increased 2001:2009 arg1 4.71±0.60 2032:2040 4.71±0.60 2032:2040 4.71±0.60 2032:2040 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 1 29 theme O-linked 224:231 arg1 O-GlcNAc 254:261 O-GlcNAc 254:261 O-GlcNAc 254:261 OBJECTIVE To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells. 36916376 1 29 theme O-linked 224:231 arg1 N-acetylglucosamine 233:251 O-linked N-acetylglucosamine 224:251 O-linked N-acetylglucosamine (O-GlcNAc) 224:262 OBJECTIVE To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells. 36916376 7 30 theme P 2784:2784 arg1 < 2786:2786 all P < 0.05 2780:2791 all P < 0.05 2780:2791 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 11 31 theme si-Akt+LPS 3646:3655 arg1 group 3657:3661 the si-Akt+LPS group 3642:3661 the si-Akt+LPS group 3642:3661 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 5 32 theme transcription 1649:1661 arg1 OGT 1462:1464 OGT 1462:1464 OGT 1462:1464 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 32 theme transcription 1649:1661 arg1 activator 1636:1644 activator 1636:1644 activator of transcription 3 (STAT3) 1636:1671 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 32 theme transcription 1649:1661 arg1 p65 1604:1606 NF-κB p65 1598:1606 NF-κB p65 1598:1606 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 32 theme transcription 1649:1661 arg1 kinase 1513:1518 extracellular signal-regulated kinase 1482:1518 extracellular signal-regulated kinase (ERK) 1482:1524 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 32 theme transcription 1649:1661 arg1 O-GlcNAc 1467:1474 O-GlcNAc 1467:1474 O-GlcNAc 1467:1474 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 32 theme transcription 1649:1661 arg1 kinase 1557:1562 p38 mitogen-activated protein kinase 1527:1562 p38 mitogen-activated protein kinase (p38MAPK) 1527:1572 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 32 theme transcription 1649:1661 arg1 Akt 1477:1479 Akt 1477:1479 Akt 1477:1479 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 32 theme transcription 1649:1661 arg1 p65 1593:1595 nuclear factor-κB p65 1575:1595 nuclear factor-κB p65 (NF-κB p65) 1575:1607 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 32 theme transcription 1649:1661 arg1 ERK 1521:1523 ERK 1521:1523 ERK 1521:1523 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 32 theme transcription 1649:1661 arg1 transducer 1621:1630 signal transducer 1614:1630 signal transducer 1614:1630 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 32 theme transcription 1649:1661 arg1 p38MAPK 1565:1571 p38MAPK 1565:1571 p38MAPK 1565:1571 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 9 33 theme inhibitor 3205:3213 arg1 pretreatment 3153:3164 pretreatment 3153:3164 pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor 3153:3231 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 5 34 theme factor-κB 1583:1591 arg1 p65 1593:1595 nuclear factor-κB p65 1575:1595 nuclear factor-κB p65 (NF-κB p65) 1575:1607 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 34 theme factor-κB 1583:1591 arg1 p65 1604:1606 NF-κB p65 1598:1606 NF-κB p65 1598:1606 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 7 35 theme phosphorylated 2407:2420 arg1 ERK 2422:2424 phosphorylated ERK 2407:2424 phosphorylated ERK 2407:2424 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 8 36 theme Akt 3016:3018 arg1 level 3007:3011 the phosphorylation level 2987:3011 the phosphorylation level of Akt in the LPS group 2987:3035 Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. 36916376 2 37 dep METHODS 336:342 arg1 cells 377:381 Human umbilical vein endothelial cells 344:381 METHODS Human umbilical vein endothelial cells (HUVEC) 336:389 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 2 37 dep METHODS 336:342 arg1 HUVEC 384:388 HUVEC 384:388 HUVEC 384:388 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 11 38 theme inflammatory 4054:4065 arg1 expression 4074:4083 the inflammatory factor expression 4050:4083 the inflammatory factor expression 4050:4083 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 4 39 theme transcription 1222:1234 arg1 levels 1236:1241 the transcription levels 1218:1241 the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)] 1218:1414 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 10 40 from change 3544:3549 arg1 VCAM-1 3554:3559 VCAM-1 3554:3559 VCAM-1 3554:3559 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 3 41 theme μmol/L 765:770 arg1 group 755:759 RhoA inhibitor+LPS group 736:759 RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS) 736:806 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 41 theme μmol/L 765:770 arg1 LPS 803:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 5 42 theme signal 1614:1619 arg1 transducer 1621:1630 signal transducer 1614:1630 signal transducer 1614:1630 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 9 43 theme OGT 3086:3088 arg1 expression 3090:3099 OGT expression 3086:3099 OGT expression 3086:3099 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 6 44 theme control 1742:1748 arg1 group 1750:1754 the blank control group 1732:1754 the blank control group 1732:1754 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 4 45 theme tumor 1292:1296 arg1 molecule-1 1395:1404 vascular cell adhesion molecule-1 1372:1404 vascular cell adhesion molecule-1 (VCAM-1) 1372:1413 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 45 theme tumor 1292:1296 arg1 necrosis 1298:1305 tumor necrosis factor-α (TNF-α) 1292:1322 tumor necrosis factor-α (TNF-α) 1292:1322 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 45 theme tumor 1292:1296 arg1 molecule-1 1348:1357 intercellular adhesion molecule-1 1325:1357 intercellular adhesion molecule-1 (ICAM-1) 1325:1366 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 5 46 theme transducer 1621:1630 arg1 phosphorylation 1443:1457 phosphorylation 1443:1457 phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) 1443:1671 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 46 theme transducer 1621:1630 arg1 expression 1429:1438 The protein expression 1417:1438 The protein expression 1417:1438 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 9 47 theme inhibitor 3223:3231 arg1 pretreatment 3153:3164 pretreatment 3153:3164 pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor 3153:3231 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 8 48 theme LPS 3027:3029 arg1 group 3031:3035 the LPS group 3023:3035 the LPS group 3023:3035 Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. 36916376 5 49 theme extracellular 1482:1494 arg1 kinase 1513:1518 extracellular signal-regulated kinase 1482:1518 extracellular signal-regulated kinase (ERK) 1482:1524 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 49 theme extracellular 1482:1494 arg1 ERK 1521:1523 ERK 1521:1523 ERK 1521:1523 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 3 50 theme 000 721:723 arg1 LPS 730:732 6983+2 000 mg/L LPS 714:732 6983+2 000 mg/L LPS 714:732 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 11 51 theme OGT 3609:3611 arg1 expression 3595:3604 the expression 3591:3604 the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group 3591:3661 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 52 theme LPS 3580:3582 arg1 group 3584:3588 the LPS group 3576:3588 the LPS group 3576:3588 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 3 53 theme mg/L 798:801 arg1 group 755:759 RhoA inhibitor+LPS group 736:759 RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS) 736:806 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 53 theme mg/L 798:801 arg1 LPS 803:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 54 theme factors 2557:2563 arg1 expression 2530:2539 the expression 2526:2539 the expression of inflammatory factors 2526:2563 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 13 55 theme O-GlcNAc 4404:4411 arg1 modification 4413:4424 O-GlcNAc modification 4404:4424 O-GlcNAc modification 4404:4424 AKT may be involved in the effect of LPS on the inhibition of O-GlcNAc modification. 36916376 12 56 theme endothelial 4146:4156 arg1 cells 4158:4162 endothelial cells 4146:4162 endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors 4146:4339 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 3 57 theme inhibitor+LPS 741:753 arg1 LPS 803:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 57 theme inhibitor+LPS 741:753 arg1 group 755:759 RhoA inhibitor+LPS group 736:759 RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS) 736:806 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 0 58 theme signaling 101:109 arg1 pathway 111:117 inflammatory signaling pathway 88:117 inflammatory signaling pathway in endothelial cells 88:138 [O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells]. 36916376 3 59 dep group 694:698 arg1 μmol/L 704:709 10 μmol/L 701:709 blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS) 504:733 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 59 dep group 694:698 arg1 Go 711:712 Go 711:712 Go 6983+2 000 mg/L LPS 711:732 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 60 theme PP2+2 962:966 arg1 LPS 977:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 60 theme PP2+2 962:966 arg1 group 945:949 serine/threonine kinase (Akt) inhibitor+LPS group 901:949 serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) 901:980 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 12 61 dep LPS 4180:4182 arg1 affects 4294:4300 affects 4294:4300 affects the expression of inflammatory factors 4294:4339 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 12 61 dep LPS 4180:4182 arg1 promotes 4184:4191 promotes 4184:4191 promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, 4184:4288 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 3 62 theme hydrochloride+2 778:792 arg1 group 755:759 RhoA inhibitor+LPS group 736:759 RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS) 736:806 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 62 theme hydrochloride+2 778:792 arg1 LPS 803:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 11 63 dep mRNA 3866:3869 arg1 0.76±0.01 3881:3889 0.76±0.01 3881:3889 0.76±0.01 3881:3889 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 63 dep mRNA 3866:3869 arg1 1.20±0.21 3942:3950 1.20±0.21 3942:3950 1.20±0.21 3942:3950 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 63 dep mRNA 3866:3869 arg1 0.99±0.02 3895:3903 0.99±0.02 3895:3903 0.99±0.02 3895:3903 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 63 dep mRNA 3866:3869 arg1 0.93±0.08 3928:3936 0.93±0.08 3928:3936 0.93±0.08 3928:3936 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 6 64 theme phosphorylated 1870:1883 arg1 ERK 1885:1887 phosphorylated ERK 1870:1887 phosphorylated ERK 1870:1887 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 10 65 from IL-6 3288:3291 arg1 group 3326:3330 the PP2+LPS group 3314:3330 the PP2+LPS group 3314:3330 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 3 66 theme phosphatidylinositol-3-kinase 809:837 arg1 LPS 895:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 66 theme phosphatidylinositol-3-kinase 809:837 arg1 group 860:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group 809:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS) 809:898 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 5 67 theme signal-regulated 1496:1511 arg1 kinase 1513:1518 extracellular signal-regulated kinase 1482:1518 extracellular signal-regulated kinase (ERK) 1482:1524 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 67 theme signal-regulated 1496:1511 arg1 ERK 1521:1523 ERK 1521:1523 ERK 1521:1523 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 0.64±0.02 2708:2716 0.64±0.02 2708:2716 0.64±0.02 2708:2716 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 2-ΔΔCt 2652:2657 2-ΔΔCt 2652:2657 2-ΔΔCt 2652:2657 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 2-ΔΔCt 2746:2751 2-ΔΔCt 2746:2751 2-ΔΔCt 2746:2751 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 mRNA 2693:2696 ICAM-1 mRNA 2686:2696 ICAM-1 mRNA (2-ΔΔCt) 2686:2705 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 1.13±0.16 2722:2730 1.13±0.16 2722:2730 1.13±0.16 2722:2730 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 2-ΔΔCt 2699:2704 2-ΔΔCt 2699:2704 2-ΔΔCt 2699:2704 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 < 2786:2786 all P < 0.05 2780:2791 all P < 0.05 2780:2791 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 0.31±0.01 2661:2669 0.31±0.01 2661:2669 0.31±0.01 2661:2669 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 mRNA 2646:2649 TNF-α mRNA 2640:2649 TNF-α mRNA (2-ΔΔCt) 2640:2658 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 0.11±0.01 2755:2763 0.11±0.01 2755:2763 0.11±0.01 2755:2763 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 mRNA 2740:2743 VCAM-1 mRNA 2733:2743 VCAM-1 mRNA (2-ΔΔCt) 2733:2752 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 0.91±0.14 2675:2683 0.91±0.14 2675:2683 0.91±0.14 2675:2683 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 68 dep 0.12±0.01 2615:2623 arg1 0.93±0.11 2769:2777 0.93±0.11 2769:2777 0.93±0.11 2769:2777 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 4 69 theme adhesion 1339:1346 arg1 necrosis 1298:1305 tumor necrosis factor-α (TNF-α) 1292:1322 tumor necrosis factor-α (TNF-α) 1292:1322 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 69 theme adhesion 1339:1346 arg1 ICAM-1 1360:1365 ICAM-1 1360:1365 ICAM-1 1360:1365 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 69 theme adhesion 1339:1346 arg1 molecule-1 1348:1357 intercellular adhesion molecule-1 1325:1357 intercellular adhesion molecule-1 (ICAM-1) 1325:1366 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 10 70 theme significant 3532:3542 arg1 change 3544:3549 no significant change 3529:3549 no significant change in VCAM-1 3529:3559 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 11 71 theme O-GlcNAc 3617:3624 arg1 modification 3626:3637 O-GlcNAc modification 3617:3637 O-GlcNAc modification 3617:3637 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 10 72 from TNF-α 3294:3298 arg1 group 3326:3330 the PP2+LPS group 3314:3330 the PP2+LPS group 3314:3330 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 6 73 theme ICAM-1 2103:2108 arg1 2-ΔΔCt 2116:2121 2-ΔΔCt 2116:2121 2-ΔΔCt 2116:2121 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 73 theme ICAM-1 2103:2108 arg1 mRNA 2110:2113 ICAM-1 mRNA 2103:2113 ICAM-1 mRNA (2-ΔΔCt) 2103:2122 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 11 74 theme modification 3626:3637 arg1 expression 3595:3604 the expression 3591:3604 the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group 3591:3661 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 7 75 from STAT3 2451:2455 arg1 cells 2476:2480 the endothelial cells 2460:2480 the endothelial cells of the OGT-OE+LPS group 2460:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 11 76 theme action 4008:4013 arg1 process 4015:4021 the action process 4004:4021 the action process of LPS 4004:4028 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 6 77 theme OGT 1775:1777 arg1 modification 1787:1798 the modification 1783:1798 the modification of O-GlcNAc 1783:1810 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 77 theme OGT 1775:1777 arg1 expression 1761:1770 the expression 1757:1770 the expression of OGT 1757:1777 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 4 78 theme transcription-polymerase 1149:1172 arg1 reaction 1180:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction 1105:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) 1105:1197 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 78 theme transcription-polymerase 1149:1172 arg1 RT-qPCR 1190:1196 RT-qPCR 1190:1196 RT-qPCR 1190:1196 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 0 79 theme [O-linked 0:8 arg1 modification 30:41 [O-linked N-acetylglucosamine modification 0:41 [O-linked N-acetylglucosamine modification induced by lipopolysaccharide 0:71 [O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells]. 36916376 7 80 from p65 2442:2444 arg1 cells 2476:2480 the endothelial cells 2460:2480 the endothelial cells of the OGT-OE+LPS group 2460:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 3 81 theme mg/L 972:975 arg1 LPS 977:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 81 theme mg/L 972:975 arg1 group 945:949 serine/threonine kinase (Akt) inhibitor+LPS group 901:949 serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) 901:980 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 10 82 from ICAM-1 3304:3309 arg1 group 3326:3330 the PP2+LPS group 3314:3330 the PP2+LPS group 3314:3330 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 3 83 theme inhibitor+LPS 846:858 arg1 LPS 895:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 83 theme inhibitor+LPS 846:858 arg1 group 860:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group 809:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS) 809:898 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 4 84 theme real-time 1105:1113 arg1 reaction 1180:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction 1105:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) 1105:1197 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 84 theme real-time 1105:1113 arg1 RT-qPCR 1190:1196 RT-qPCR 1190:1196 RT-qPCR 1190:1196 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 0 85 link [O-linked 0:8 arg1 modification 30:41 [O-linked N-acetylglucosamine modification 0:41 [O-linked N-acetylglucosamine modification induced by lipopolysaccharide 0:71 [O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells]. 36916376 2 86 theme growth 440:445 arg1 phase 447:451 logarithmic growth phase 428:451 logarithmic growth phase 428:451 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 9 87 theme LPS 3070:3072 arg1 group 3074:3078 the LPS group 3066:3078 the LPS group 3066:3078 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 1 88 theme endothelial 317:327 arg1 cells 329:333 endothelial cells 317:333 endothelial cells 317:333 OBJECTIVE To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells. 36916376 3 89 theme RNA 1004:1006 arg1 LPS 1066:1068 si-Akt+2 000 mg/L LPS 1048:1068 si-Akt+2 000 mg/L LPS 1048:1068 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 89 theme RNA 1004:1006 arg1 group 1041:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group 986:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS) 986:1069 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 90 theme PI3K 840:843 arg1 LPS 895:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 90 theme PI3K 840:843 arg1 group 860:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group 809:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS) 809:898 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 91 theme OGT-OE+LPS 2489:2498 arg1 group 2500:2504 the OGT-OE+LPS group 2485:2504 the OGT-OE+LPS group 2485:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 11 92 dep decreased 3757:3765 arg1 0.99±0.09 3802:3810 0.99±0.09 3802:3810 0.99±0.09 3802:3810 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 92 dep decreased 3757:3765 arg1 0.75±0.03 3788:3796 0.75±0.03 3788:3796 0.75±0.03 3788:3796 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 3 93 theme plasmid 615:621 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 93 theme plasmid 615:621 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 10 94 dep 1.46±0.16 3382:3390 arg1 mRNA 3460:3463 ICAM-1 mRNA 3453:3463 ICAM-1 mRNA (2-ΔΔCt) 3453:3472 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 94 dep 1.46±0.16 3382:3390 arg1 2.04±0.13 3489:3497 2.04±0.13 3489:3497 2.04±0.13 3489:3497 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 94 dep 1.46±0.16 3382:3390 arg1 2-ΔΔCt 3466:3471 2-ΔΔCt 3466:3471 2-ΔΔCt 3466:3471 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 94 dep 1.46±0.16 3382:3390 arg1 0.98±0.14 3428:3436 0.98±0.14 3428:3436 0.98±0.14 3428:3436 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 94 dep 1.46±0.16 3382:3390 arg1 mRNA 3413:3416 TNF-α mRNA 3407:3416 TNF-α mRNA (2-ΔΔCt) 3407:3425 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 94 dep 1.46±0.16 3382:3390 arg1 1.76±0.10 3442:3450 1.76±0.10 3442:3450 1.76±0.10 3442:3450 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 94 dep 1.46±0.16 3382:3390 arg1 1.39±0.24 3475:3483 1.39±0.24 3475:3483 1.39±0.24 3475:3483 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 94 dep 1.46±0.16 3382:3390 arg1 2-ΔΔCt 3419:3424 2-ΔΔCt 3419:3424 2-ΔΔCt 3419:3424 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 94 dep 1.46±0.16 3382:3390 arg1 < 3506:3506 all P < 0.05 3500:3511 all P < 0.05 3500:3511 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 5 95 theme kinase 1513:1518 arg1 phosphorylation 1443:1457 phosphorylation 1443:1457 phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) 1443:1671 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 95 theme kinase 1513:1518 arg1 expression 1429:1438 The protein expression 1417:1438 The protein expression 1417:1438 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 3 96 theme small 986:990 arg1 siRNA 1009:1013 siRNA 1009:1013 siRNA 1009:1013 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 96 theme small 986:990 arg1 RNA 1004:1006 small interfering RNA 986:1006 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS) 986:1069 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 97 theme level 2831:2835 arg1 increase 2815:2822 the increase 2811:2822 the increase of OGT level 2811:2835 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 3 98 theme μmol/L 869:874 arg1 LPS 895:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 98 theme μmol/L 869:874 arg1 group 860:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group 809:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS) 809:898 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 4 99 theme quantitative 1128:1139 arg1 reaction 1180:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction 1105:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) 1105:1197 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 99 theme quantitative 1128:1139 arg1 RT-qPCR 1190:1196 RT-qPCR 1190:1196 RT-qPCR 1190:1196 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 3 100 theme kinase 665:670 arg1 C 672:672 protein kinase C 657:672 protein kinase C (PKC) 657:678 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 100 theme kinase 665:670 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 100 theme kinase 665:670 arg1 PKC 675:677 PKC 675:677 PKC 675:677 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 101 theme blank 504:508 arg1 C 672:672 protein kinase C 657:672 protein kinase C (PKC) 657:678 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 101 theme blank 504:508 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 101 theme blank 504:508 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 101 theme blank 504:508 arg1 group 529:533 LPS group 525:533 LPS group (2 000 mg/L LPS) 525:550 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 102 dep decreased 2584:2592 arg1 0.90±0.17 2629:2637 0.90±0.17 2629:2637 0.90±0.17 2629:2637 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 102 dep decreased 2584:2592 arg1 0.12±0.01 2615:2623 0.12±0.01 2615:2623 0.12±0.01 2615:2623 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 3 103 theme treated 1016:1022 arg1 LPS 1066:1068 si-Akt+2 000 mg/L LPS 1048:1068 si-Akt+2 000 mg/L LPS 1048:1068 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 103 theme treated 1016:1022 arg1 group 1041:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group 986:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS) 986:1069 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 6 104 theme inflammatory 2324:2335 arg1 cytokines 2337:2345 inflammatory cytokines 2324:2345 inflammatory cytokines expression 2324:2356 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 4 105 theme reverse 1141:1147 arg1 reaction 1180:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction 1105:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) 1105:1197 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 105 theme reverse 1141:1147 arg1 RT-qPCR 1190:1196 RT-qPCR 1190:1196 RT-qPCR 1190:1196 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 106 theme cell 1381:1384 arg1 necrosis 1298:1305 tumor necrosis factor-α (TNF-α) 1292:1322 tumor necrosis factor-α (TNF-α) 1292:1322 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 106 theme cell 1381:1384 arg1 VCAM-1 1407:1412 VCAM-1 1407:1412 VCAM-1 1407:1412 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 106 theme cell 1381:1384 arg1 molecule-1 1395:1404 vascular cell adhesion molecule-1 1372:1404 vascular cell adhesion molecule-1 (VCAM-1) 1372:1413 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 3 107 theme mg/L 646:649 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 107 theme mg/L 646:649 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 6 108 theme LPS 1819:1821 arg1 group 1823:1827 the LPS group 1815:1827 the LPS group 1815:1827 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 5 109 theme nuclear 1575:1581 arg1 p65 1593:1595 nuclear factor-κB p65 1575:1595 nuclear factor-κB p65 (NF-κB p65) 1575:1607 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 109 theme nuclear 1575:1581 arg1 p65 1604:1606 NF-κB p65 1598:1606 NF-κB p65 1598:1606 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 2 110 theme endothelial 365:375 arg1 cells 377:381 Human umbilical vein endothelial cells 344:381 METHODS Human umbilical vein endothelial cells (HUVEC) 336:389 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 2 110 theme endothelial 365:375 arg1 HUVEC 384:388 HUVEC 384:388 HUVEC 384:388 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 10 111 theme TNF-α 3294:3298 arg1 levels 3278:3283 the transcript levels 3263:3283 the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group 3263:3330 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 7 112 from expressions 2392:2402 arg1 cells 2476:2480 the endothelial cells 2460:2480 the endothelial cells of the OGT-OE+LPS group 2460:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 12 113 theme signaling 4228:4236 arg1 pathways 4238:4245 inflammatory signaling pathways 4215:4245 inflammatory signaling pathways 4215:4245 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 5 114 theme p65 1593:1595 arg1 phosphorylation 1443:1457 phosphorylation 1443:1457 phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) 1443:1671 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 114 theme p65 1593:1595 arg1 expression 1429:1438 The protein expression 1417:1438 The protein expression 1417:1438 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 3 115 theme OGT+2 636:640 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 115 theme OGT+2 636:640 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 6 116 theme TNF-α 2057:2061 arg1 2-ΔΔCt 2069:2074 2-ΔΔCt 2069:2074 2-ΔΔCt 2069:2074 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 116 theme TNF-α 2057:2061 arg1 mRNA 2063:2066 TNF-α mRNA 2057:2066 TNF-α mRNA (2-ΔΔCt) 2057:2075 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 3 117 theme LPS 525:527 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 117 theme LPS 525:527 arg1 LPS 547:549 2 000 mg/L LPS 536:549 2 000 mg/L LPS 536:549 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 117 theme LPS 525:527 arg1 group 529:533 LPS group 525:533 LPS group (2 000 mg/L LPS) 525:550 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 10 118 theme IL-6 3288:3291 arg1 levels 3278:3283 the transcript levels 3263:3283 the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group 3263:3330 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 7 119 theme VCAM-1 2733:2738 arg1 2-ΔΔCt 2746:2751 2-ΔΔCt 2746:2751 2-ΔΔCt 2746:2751 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 119 theme VCAM-1 2733:2738 arg1 mRNA 2740:2743 VCAM-1 mRNA 2733:2743 VCAM-1 mRNA (2-ΔΔCt) 2733:2752 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 3 120 theme 000 886:888 arg1 LPS 895:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 120 theme 000 886:888 arg1 group 860:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group 809:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS) 809:898 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 11 121 dep 0.75±0.03 3788:3796 arg1 mRNA 3866:3869 ICAM-1 mRNA 3859:3869 ICAM-1 mRNA (2-ΔΔCt) 3859:3878 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 121 dep 0.75±0.03 3788:3796 arg1 2-ΔΔCt 3872:3877 2-ΔΔCt 3872:3877 2-ΔΔCt 3872:3877 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 121 dep 0.75±0.03 3788:3796 arg1 < 3959:3959 all P < 0.05 3953:3964 all P < 0.05 3953:3964 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 121 dep 0.75±0.03 3788:3796 arg1 0.69±0.01 3834:3842 0.69±0.01 3834:3842 0.69±0.01 3834:3842 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 121 dep 0.75±0.03 3788:3796 arg1 mRNA 3819:3822 TNF-α mRNA 3813:3822 TNF-α mRNA (2-ΔΔCt) 3813:3831 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 121 dep 0.75±0.03 3788:3796 arg1 mRNA 3913:3916 VCAM-1 mRNA 3906:3916 VCAM-1 mRNA (2-ΔΔCt) 3906:3925 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 121 dep 0.75±0.03 3788:3796 arg1 1.10±0.08 3848:3856 1.10±0.08 3848:3856 1.10±0.08 3848:3856 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 121 dep 0.75±0.03 3788:3796 arg1 2-ΔΔCt 3825:3830 2-ΔΔCt 3825:3830 2-ΔΔCt 3825:3830 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 13 122 from effect 4369:4374 arg1 inhibition 4390:4399 the inhibition 4386:4399 the inhibition of O-GlcNAc modification 4386:4424 AKT may be involved in the effect of LPS on the inhibition of O-GlcNAc modification. 36916376 3 123 theme protein 657:663 arg1 C 672:672 protein kinase C 657:672 protein kinase C (PKC) 657:678 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 123 theme protein 657:663 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 123 theme protein 657:663 arg1 PKC 675:677 PKC 675:677 PKC 675:677 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 124 theme group 518:522 arg1 group 694:698 blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group 504:698 blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS) 504:733 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 6 125 theme cytokines 1967:1975 arg1 levels 1944:1949 the transcript levels 1929:1949 the transcript levels of inflammatory cytokines 1929:1975 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 12 126 theme partial 4193:4199 arg1 activation 4201:4210 partial activation 4193:4210 partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, 4193:4288 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 3 127 theme kinase 918:923 arg1 LPS 977:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 127 theme kinase 918:923 arg1 group 945:949 serine/threonine kinase (Akt) inhibitor+LPS group 901:949 serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) 901:980 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 6 128 theme p38MAPK 1890:1896 arg1 expressions 1855:1865 the expressions 1851:1865 the expressions of phosphorylated ERK, p38MAPK, and STAT3 1851:1907 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 129 theme O-GlcNAc 2247:2254 arg1 modification 2256:2267 O-GlcNAc modification 2247:2267 O-GlcNAc modification 2247:2267 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 3 130 theme 000 538:540 arg1 LPS 547:549 2 000 mg/L LPS 536:549 2 000 mg/L LPS 536:549 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 130 theme 000 538:540 arg1 group 529:533 LPS group 525:533 LPS group (2 000 mg/L LPS) 525:550 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 10 131 theme ICAM-1 3304:3309 arg1 levels 3278:3283 the transcript levels 3263:3283 the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group 3263:3330 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 1 132 theme inflammatory 283:294 arg1 pathway 306:312 the inflammatory signaling pathway 279:312 the inflammatory signaling pathway of endothelial cells 279:333 OBJECTIVE To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells. 36916376 3 133 theme si-Akt+2 1048:1055 arg1 LPS 1066:1068 si-Akt+2 000 mg/L LPS 1048:1068 si-Akt+2 000 mg/L LPS 1048:1068 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 133 theme si-Akt+2 1048:1055 arg1 group 1041:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group 986:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS) 986:1069 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 4 134 dep cytokines 1259:1267 arg1 IL-6 1285:1288 IL-6 1285:1288 IL-6 1285:1288 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 134 dep cytokines 1259:1267 arg1 [interleukin-6 1269:1282 [interleukin-6 1269:1282 [interleukin-6 1269:1282 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 6 135 theme VCAM-1 2150:2155 arg1 2-ΔΔCt 2163:2168 2-ΔΔCt 2163:2168 2-ΔΔCt 2163:2168 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 135 theme VCAM-1 2150:2155 arg1 mRNA 2157:2160 VCAM-1 mRNA 2150:2160 VCAM-1 mRNA (2-ΔΔCt) 2150:2169 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 8 136 theme control 2972:2978 arg1 group 2980:2984 the blank control group 2962:2984 the blank control group 2962:2984 Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. 36916376 4 137 theme adhesion 1386:1393 arg1 necrosis 1298:1305 tumor necrosis factor-α (TNF-α) 1292:1322 tumor necrosis factor-α (TNF-α) 1292:1322 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 137 theme adhesion 1386:1393 arg1 VCAM-1 1407:1412 VCAM-1 1407:1412 VCAM-1 1407:1412 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 137 theme adhesion 1386:1393 arg1 molecule-1 1395:1404 vascular cell adhesion molecule-1 1372:1404 vascular cell adhesion molecule-1 (VCAM-1) 1372:1413 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 5 138 theme kinase 1557:1562 arg1 phosphorylation 1443:1457 phosphorylation 1443:1457 phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) 1443:1671 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 138 theme kinase 1557:1562 arg1 expression 1429:1438 The protein expression 1417:1438 The protein expression 1417:1438 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 9 139 theme PKC 3169:3171 arg1 inhibitor 3173:3181 PKC inhibitor 3169:3181 PKC inhibitor 3169:3181 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 6 140 theme transcript 1933:1942 arg1 levels 1944:1949 the transcript levels 1929:1949 the transcript levels of inflammatory cytokines 1929:1975 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 7 141 theme STAT3 2451:2455 arg1 expressions 2392:2402 the expressions 2388:2402 the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group 2388:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 3 142 theme inhibitor+LPS 931:943 arg1 LPS 977:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 142 theme inhibitor+LPS 931:943 arg1 group 945:949 serine/threonine kinase (Akt) inhibitor+LPS group 901:949 serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) 901:980 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 12 143 theme O-GlcNAc 4121:4128 arg1 modification 4130:4141 O-GlcNAc modification 4121:4141 O-GlcNAc modification 4121:4141 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 5 144 theme O-GlcNAc 1467:1474 arg1 phosphorylation 1443:1457 phosphorylation 1443:1457 phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) 1443:1671 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 144 theme O-GlcNAc 1467:1474 arg1 expression 1429:1438 The protein expression 1417:1438 The protein expression 1417:1438 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 2 145 theme umbilical 350:358 arg1 cells 377:381 Human umbilical vein endothelial cells 344:381 METHODS Human umbilical vein endothelial cells (HUVEC) 336:389 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 2 145 theme umbilical 350:358 arg1 HUVEC 384:388 HUVEC 384:388 HUVEC 384:388 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 6 146 theme STAT3 1903:1907 arg1 expressions 1855:1865 the expressions 1851:1865 the expressions of phosphorylated ERK, p38MAPK, and STAT3 1851:1907 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 1 147 theme -induced 199:206 arg1 modification 208:219 the lipopolysaccharide (LPS)-induced modification 171:219 the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) 171:262 OBJECTIVE To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells. 36916376 12 148 theme factors 4333:4339 arg1 expression 4306:4315 the expression 4302:4315 the expression of inflammatory factors 4302:4339 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 3 149 theme Akt 926:928 arg1 LPS 977:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 149 theme Akt 926:928 arg1 group 945:949 serine/threonine kinase (Akt) inhibitor+LPS group 901:949 serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) 901:980 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 4 150 theme LPS 1090:1092 arg1 treatment 1094:1102 LPS treatment 1090:1102 LPS treatment 1090:1102 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 6 151 from expression 1761:1770 arg1 group 1823:1827 the LPS group 1815:1827 the LPS group 1815:1827 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 5 152 theme Akt 1477:1479 arg1 phosphorylation 1443:1457 phosphorylation 1443:1457 phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) 1443:1671 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 152 theme Akt 1477:1479 arg1 expression 1429:1438 The protein expression 1417:1438 The protein expression 1417:1438 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 6 153 theme cytokines 2337:2345 arg1 expression 2347:2356 inflammatory cytokines expression 2324:2356 inflammatory cytokines expression 2324:2356 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 10 154 theme P 3504:3504 arg1 < 3506:3506 all P < 0.05 3500:3511 all P < 0.05 3500:3511 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 9 155 theme inhibitor 3189:3197 arg1 pretreatment 3153:3164 pretreatment 3153:3164 pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor 3153:3231 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 3 156 theme O-GlcNAc 553:560 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 156 theme O-GlcNAc 553:560 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 156 theme O-GlcNAc 553:560 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 157 theme NF-κB 2436:2440 arg1 p65 2442:2444 NF-κB p65 2436:2444 NF-κB p65 2436:2444 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 0 158 from pathway 111:117 arg1 cells 134:138 endothelial cells 122:138 endothelial cells 122:138 [O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells]. 36916376 8 159 theme phosphorylation 2991:3005 arg1 level 3007:3011 the phosphorylation level 2987:3011 the phosphorylation level of Akt in the LPS group 2987:3035 Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. 36916376 11 160 theme factor 4067:4072 arg1 expression 4074:4083 the inflammatory factor expression 4050:4083 the inflammatory factor expression 4050:4083 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 3 161 theme inhibitor+LPS 680:692 arg1 group 694:698 blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group 504:698 blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS) 504:733 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 162 theme OGT 575:577 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 162 theme OGT 575:577 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 162 theme OGT 575:577 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 9 163 theme PI3K 3200:3203 arg1 inhibitor 3205:3213 PI3K inhibitor 3200:3213 PI3K inhibitor 3200:3213 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 1 164 theme N-acetylglucosamine 233:251 arg1 modification 208:219 the lipopolysaccharide (LPS)-induced modification 171:219 the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) 171:262 OBJECTIVE To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells. 36916376 7 165 theme p38MAPK 2427:2433 arg1 expressions 2392:2402 the expressions 2388:2402 the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group 2388:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 166 theme partial 2855:2861 arg1 activation 2863:2872 the partial activation 2851:2872 the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation 2851:2945 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 12 167 theme inflammatory 4320:4331 arg1 factors 4333:4339 inflammatory factors 4320:4339 inflammatory factors 4320:4339 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 5 168 theme OGT 1462:1464 arg1 phosphorylation 1443:1457 phosphorylation 1443:1457 phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) 1443:1671 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 168 theme OGT 1462:1464 arg1 expression 1429:1438 The protein expression 1417:1438 The protein expression 1417:1438 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 3 169 theme 6983+2 714:719 arg1 LPS 730:732 6983+2 000 mg/L LPS 714:732 6983+2 000 mg/L LPS 714:732 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 170 theme pathway 2913:2919 arg1 activation 2863:2872 the partial activation 2851:2872 the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation 2851:2945 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 3 171 theme transferase 562:572 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 171 theme transferase 562:572 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 171 theme transferase 562:572 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 172 theme endothelial 2881:2891 arg1 pathway 2913:2919 the endothelial inflammatory signal pathway 2877:2919 the endothelial inflammatory signal pathway under the LPS stimulation 2877:2945 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 11 173 theme TNF-α 3813:3817 arg1 2-ΔΔCt 3825:3830 2-ΔΔCt 3825:3830 2-ΔΔCt 3825:3830 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 173 theme TNF-α 3813:3817 arg1 mRNA 3819:3822 TNF-α mRNA 3813:3822 TNF-α mRNA (2-ΔΔCt) 3813:3831 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 7 174 theme ERK 2422:2424 arg1 expressions 2392:2402 the expressions 2388:2402 the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group 2388:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 6 175 theme P 2201:2201 arg1 < 2203:2203 all P < 0.05 2197:2208 all P < 0.05 2197:2208 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 7 176 theme LPS 2377:2379 arg1 group 2381:2385 the LPS group 2373:2385 the LPS group 2373:2385 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 6 177 theme inflammatory 2279:2290 arg1 pathways 2302:2309 inflammatory signaling pathways 2279:2309 inflammatory signaling pathways 2279:2309 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 2-ΔΔCt 2163:2168 2-ΔΔCt 2163:2168 2-ΔΔCt 2163:2168 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 mRNA 2110:2113 ICAM-1 mRNA 2103:2113 ICAM-1 mRNA (2-ΔΔCt) 2103:2122 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 1.02±0.21 2139:2147 1.02±0.21 2139:2147 1.02±0.21 2139:2147 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 < 2203:2203 all P < 0.05 2197:2208 all P < 0.05 2197:2208 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 1.89±0.11 2078:2086 1.89±0.11 2078:2086 1.89±0.11 2078:2086 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 2.94±0.57 2172:2180 2.94±0.57 2172:2180 2.94±0.57 2172:2180 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 2-ΔΔCt 2116:2121 2-ΔΔCt 2116:2121 2-ΔΔCt 2116:2121 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 1.04±0.35 2092:2100 1.04±0.35 2092:2100 1.04±0.35 2092:2100 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 mRNA 2063:2066 TNF-α mRNA 2057:2066 TNF-α mRNA (2-ΔΔCt) 2057:2075 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 1.01±0.17 2186:2194 1.01±0.17 2186:2194 1.01±0.17 2186:2194 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 mRNA 2157:2160 VCAM-1 mRNA 2150:2160 VCAM-1 mRNA (2-ΔΔCt) 2150:2169 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 2.06±0.18 2125:2133 2.06±0.18 2125:2133 2.06±0.18 2125:2133 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 178 dep 4.71±0.60 2032:2040 arg1 2-ΔΔCt 2069:2074 2-ΔΔCt 2069:2074 2-ΔΔCt 2069:2074 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 11 179 theme transcript 3689:3698 arg1 levels 3700:3705 the transcript levels 3685:3705 the transcript levels of inflammatory cytokines 3685:3731 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 3 180 theme OGT-OE 596:601 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 180 theme OGT-OE 596:601 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 180 theme OGT-OE 596:601 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 9 181 theme Akt 3219:3221 arg1 inhibitor 3223:3231 Akt inhibitor 3219:3231 Akt inhibitor 3219:3231 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 3 182 theme Rhoin 772:776 arg1 group 755:759 RhoA inhibitor+LPS group 736:759 RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS) 736:806 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 182 theme Rhoin 772:776 arg1 LPS 803:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 10 183 from group 3326:3330 arg1 levels 3278:3283 the transcript levels 3263:3283 the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group 3263:3330 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 6 184 theme blank 1736:1740 arg1 group 1750:1754 the blank control group 1732:1754 the blank control group 1732:1754 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 0 185 theme inflammatory 88:99 arg1 pathway 111:117 inflammatory signaling pathway 88:117 inflammatory signaling pathway in endothelial cells 88:138 [O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells]. 36916376 3 186 theme overexpression 580:593 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 186 theme overexpression 580:593 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 186 theme overexpression 580:593 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 10 187 theme TNF-α 3407:3411 arg1 2-ΔΔCt 3419:3424 2-ΔΔCt 3419:3424 2-ΔΔCt 3419:3424 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 187 theme TNF-α 3407:3411 arg1 mRNA 3413:3416 TNF-α mRNA 3407:3416 TNF-α mRNA (2-ΔΔCt) 3407:3425 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 188 theme LPS 3252:3254 arg1 group 3256:3260 the LPS group 3248:3260 the LPS group 3248:3260 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 189 theme transcript 3267:3276 arg1 levels 3278:3283 the transcript levels 3263:3283 the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group 3263:3330 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 3 190 theme mg/L 1061:1064 arg1 LPS 1066:1068 si-Akt+2 000 mg/L LPS 1048:1068 si-Akt+2 000 mg/L LPS 1048:1068 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 190 theme mg/L 1061:1064 arg1 group 1041:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group 986:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS) 986:1069 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 11 191 theme inflammatory 3710:3721 arg1 cytokines 3723:3731 inflammatory cytokines 3710:3731 inflammatory cytokines 3710:3731 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 3 192 theme mg/L 725:728 arg1 LPS 730:732 6983+2 000 mg/L LPS 714:732 6983+2 000 mg/L LPS 714:732 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 5 193 theme mitogen-activated 1531:1547 arg1 kinase 1557:1562 p38 mitogen-activated protein kinase 1527:1562 p38 mitogen-activated protein kinase (p38MAPK) 1527:1572 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 193 theme mitogen-activated 1531:1547 arg1 p38MAPK 1565:1571 p38MAPK 1565:1571 p38MAPK 1565:1571 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 3 194 theme μmol/L 955:960 arg1 LPS 977:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 194 theme μmol/L 955:960 arg1 group 945:949 serine/threonine kinase (Akt) inhibitor+LPS group 901:949 serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) 901:980 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 13 195 theme LPS 4379:4381 arg1 effect 4369:4374 the effect 4365:4374 the effect of LPS on the inhibition of O-GlcNAc modification 4365:4424 AKT may be involved in the effect of LPS on the inhibition of O-GlcNAc modification. 36916376 13 196 theme modification 4413:4424 arg1 inhibition 4390:4399 the inhibition 4386:4399 the inhibition of O-GlcNAc modification 4386:4424 AKT may be involved in the effect of LPS on the inhibition of O-GlcNAc modification. 36916376 7 197 theme OGT 2827:2829 arg1 level 2831:2835 OGT level 2827:2835 OGT level 2827:2835 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 0 198 theme endothelial 122:132 arg1 cells 134:138 endothelial cells 122:138 endothelial cells 122:138 [O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells]. 36916376 8 199 from level 3007:3011 arg1 group 3031:3035 the LPS group 3023:3035 the LPS group 3023:3035 Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. 36916376 6 200 theme ERK 1885:1887 arg1 expressions 1855:1865 the expressions 1851:1865 the expressions of phosphorylated ERK, p38MAPK, and STAT3 1851:1907 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 3 201 theme 000 794:796 arg1 group 755:759 RhoA inhibitor+LPS group 736:759 RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS) 736:806 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 201 theme 000 794:796 arg1 LPS 803:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 202 theme inflammatory 2893:2904 arg1 pathway 2913:2919 the endothelial inflammatory signal pathway 2877:2919 the endothelial inflammatory signal pathway under the LPS stimulation 2877:2945 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 203 theme inflammatory 2544:2555 arg1 factors 2557:2563 inflammatory factors 2544:2563 inflammatory factors 2544:2563 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 1 204 link O-linked 224:231 arg1 O-GlcNAc 254:261 O-GlcNAc 254:261 O-GlcNAc 254:261 OBJECTIVE To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells. 36916376 1 204 link O-linked 224:231 arg1 N-acetylglucosamine 233:251 O-linked N-acetylglucosamine 224:251 O-linked N-acetylglucosamine (O-GlcNAc) 224:262 OBJECTIVE To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells. 36916376 5 205 theme Western 1692:1698 arg1 blotting 1700:1707 Western blotting 1692:1707 Western blotting 1692:1707 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 3 206 theme RhoA 736:739 arg1 LPS 803:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS 762:805 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 206 theme RhoA 736:739 arg1 group 755:759 RhoA inhibitor+LPS group 736:759 RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS) 736:806 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 11 207 from expression 3595:3604 arg1 group 3657:3661 the si-Akt+LPS group 3642:3661 the si-Akt+LPS group 3642:3661 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 208 theme LPS 4026:4028 arg1 process 4015:4021 the action process 4004:4021 the action process of LPS 4004:4028 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 4 209 theme intercellular 1325:1337 arg1 necrosis 1298:1305 tumor necrosis factor-α (TNF-α) 1292:1322 tumor necrosis factor-α (TNF-α) 1292:1322 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 209 theme intercellular 1325:1337 arg1 ICAM-1 1360:1365 ICAM-1 1360:1365 ICAM-1 1360:1365 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 209 theme intercellular 1325:1337 arg1 molecule-1 1348:1357 intercellular adhesion molecule-1 1325:1357 intercellular adhesion molecule-1 (ICAM-1) 1325:1366 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 0 210 theme N-acetylglucosamine 10:28 arg1 modification 30:41 [O-linked N-acetylglucosamine modification 0:41 [O-linked N-acetylglucosamine modification induced by lipopolysaccharide 0:71 [O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells]. 36916376 4 211 theme inflammatory 1246:1257 arg1 cytokines 1259:1267 inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)] 1246:1414 inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)] 1246:1414 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 3 212 theme 000 968:970 arg1 LPS 977:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 10 μmol/L PP2+2 000 mg/L LPS 952:979 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 212 theme 000 968:970 arg1 group 945:949 serine/threonine kinase (Akt) inhibitor+LPS group 901:949 serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) 901:980 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 12 213 from level 4112:4116 arg1 cells 4158:4162 endothelial cells 4146:4162 endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors 4146:4339 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 4 214 theme treatment 1094:1102 arg1 hours 1081:1085 24 hours 1078:1085 24 hours of LPS treatment 1078:1102 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 7 215 theme LPS 2931:2933 arg1 stimulation 2935:2945 the LPS stimulation 2927:2945 the LPS stimulation 2927:2945 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 5 216 theme p38 1527:1529 arg1 kinase 1557:1562 p38 mitogen-activated protein kinase 1527:1562 p38 mitogen-activated protein kinase (p38MAPK) 1527:1572 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 216 theme p38 1527:1529 arg1 p38MAPK 1565:1571 p38MAPK 1565:1571 p38MAPK 1565:1571 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 3 217 theme interfering 992:1002 arg1 siRNA 1009:1013 siRNA 1009:1013 siRNA 1009:1013 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 217 theme interfering 992:1002 arg1 RNA 1004:1006 small interfering RNA 986:1006 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS) 986:1069 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 218 theme TNF-α 2640:2644 arg1 2-ΔΔCt 2652:2657 2-ΔΔCt 2652:2657 2-ΔΔCt 2652:2657 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 7 218 theme TNF-α 2640:2644 arg1 mRNA 2646:2649 TNF-α mRNA 2640:2649 TNF-α mRNA (2-ΔΔCt) 2640:2658 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 4 219 theme fluorescence 1115:1126 arg1 reaction 1180:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction 1105:1187 real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) 1105:1197 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 219 theme fluorescence 1115:1126 arg1 RT-qPCR 1190:1196 RT-qPCR 1190:1196 RT-qPCR 1190:1196 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 10 220 theme [IL-6 3361:3365 arg1 mRNA 3367:3370 [IL-6 mRNA 3361:3370 [IL-6 mRNA (2-ΔΔCt) 3361:3379 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 220 theme [IL-6 3361:3365 arg1 2-ΔΔCt 3373:3378 2-ΔΔCt 3373:3378 2-ΔΔCt 3373:3378 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 2 221 theme logarithmic 428:438 arg1 phase 447:451 logarithmic growth phase 428:451 logarithmic growth phase 428:451 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 1 222 theme cells 329:333 arg1 pathway 306:312 the inflammatory signaling pathway 279:312 the inflammatory signaling pathway of endothelial cells 279:333 OBJECTIVE To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells. 36916376 11 223 theme ICAM-1 3859:3864 arg1 < 3959:3959 all P < 0.05 3953:3964 all P < 0.05 3953:3964 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 223 theme ICAM-1 3859:3864 arg1 mRNA 3866:3869 ICAM-1 mRNA 3859:3869 ICAM-1 mRNA (2-ΔΔCt) 3859:3878 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 223 theme ICAM-1 3859:3864 arg1 mRNA 3913:3916 VCAM-1 mRNA 3906:3916 VCAM-1 mRNA (2-ΔΔCt) 3906:3925 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 223 theme ICAM-1 3859:3864 arg1 2-ΔΔCt 3872:3877 2-ΔΔCt 3872:3877 2-ΔΔCt 3872:3877 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 7 224 theme group 2500:2504 arg1 cells 2476:2480 the endothelial cells 2460:2480 the endothelial cells of the OGT-OE+LPS group 2460:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 11 225 theme P 3957:3957 arg1 < 3959:3959 all P < 0.05 3953:3964 all P < 0.05 3953:3964 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 11 225 theme P 3957:3957 arg1 mRNA 3866:3869 ICAM-1 mRNA 3859:3869 ICAM-1 mRNA (2-ΔΔCt) 3859:3878 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 3 226 theme +LPS 603:606 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 226 theme +LPS 603:606 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 226 theme +LPS 603:606 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 4 227 dep [interleukin-6 1269:1282 arg1 molecule-1 1395:1404 vascular cell adhesion molecule-1 1372:1404 vascular cell adhesion molecule-1 (VCAM-1) 1372:1413 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 227 dep [interleukin-6 1269:1282 arg1 necrosis 1298:1305 tumor necrosis factor-α (TNF-α) 1292:1322 tumor necrosis factor-α (TNF-α) 1292:1322 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 227 dep [interleukin-6 1269:1282 arg1 molecule-1 1348:1357 intercellular adhesion molecule-1 1325:1357 intercellular adhesion molecule-1 (ICAM-1) 1325:1366 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 3 228 theme SL-2052+2 876:884 arg1 LPS 895:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 1 μmol/L SL-2052+2 000 mg/L LPS 867:897 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 228 theme SL-2052+2 876:884 arg1 group 860:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group 809:864 phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS) 809:898 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 229 theme 000 642:644 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 229 theme 000 642:644 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 230 theme control 510:516 arg1 C 672:672 protein kinase C 657:672 protein kinase C (PKC) 657:678 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 230 theme control 510:516 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 230 theme control 510:516 arg1 group 518:522 blank control group 504:522 blank control group 504:522 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 230 theme control 510:516 arg1 group 529:533 LPS group 525:533 LPS group (2 000 mg/L LPS) 525:550 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 7 231 from cells 2476:2480 arg1 expressions 2392:2402 the expressions 2388:2402 the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group 2388:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36916376 4 232 theme vascular 1372:1379 arg1 necrosis 1298:1305 tumor necrosis factor-α (TNF-α) 1292:1322 tumor necrosis factor-α (TNF-α) 1292:1322 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 232 theme vascular 1372:1379 arg1 VCAM-1 1407:1412 VCAM-1 1407:1412 VCAM-1 1407:1412 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 4 232 theme vascular 1372:1379 arg1 molecule-1 1395:1404 vascular cell adhesion molecule-1 1372:1404 vascular cell adhesion molecule-1 (VCAM-1) 1372:1413 After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. 36916376 10 233 from levels 3278:3283 arg1 group 3326:3330 the PP2+LPS group 3314:3330 the PP2+LPS group 3314:3330 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 3 234 theme transfection 623:634 arg1 LPS 651:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 plasmid transfection OGT+2 000 mg/L LPS 615:653 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 234 theme transfection 623:634 arg1 group 608:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group 553:612 O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS) 553:654 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 2 235 theme vein 360:363 arg1 cells 377:381 Human umbilical vein endothelial cells 344:381 METHODS Human umbilical vein endothelial cells (HUVEC) 336:389 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 2 235 theme vein 360:363 arg1 HUVEC 384:388 HUVEC 384:388 HUVEC 384:388 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 9 236 theme O-GlcNAc 3105:3112 arg1 modification 3114:3125 O-GlcNAc modification 3105:3125 O-GlcNAc modification 3105:3125 Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. 36916376 11 237 theme cytokines 3723:3731 arg1 levels 3700:3705 the transcript levels 3685:3705 the transcript levels of inflammatory cytokines 3685:3731 Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2-ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2-ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2-ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. 36916376 3 238 theme si-AKT 1029:1034 arg1 LPS 1066:1068 si-Akt+2 000 mg/L LPS 1048:1068 si-Akt+2 000 mg/L LPS 1048:1068 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 3 238 theme si-AKT 1029:1034 arg1 group 1041:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group 986:1045 small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS) 986:1069 Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). 36916376 12 239 theme inflammatory 4215:4226 arg1 pathways 4238:4245 inflammatory signaling pathways 4215:4245 inflammatory signaling pathways 4215:4245 CONCLUSIONS The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. 36916376 2 240 from cells 419:423 arg1 phase 447:451 logarithmic growth phase 428:451 logarithmic growth phase 428:451 METHODS Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. 36916376 5 241 theme protein 1421:1427 arg1 expression 1429:1438 The protein expression 1417:1438 The protein expression 1417:1438 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 6 242 theme O-GlcNAc 1803:1810 arg1 modification 1787:1798 the modification 1783:1798 the modification of O-GlcNAc 1783:1810 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 6 242 theme O-GlcNAc 1803:1810 arg1 expression 1761:1770 the expression 1757:1770 the expression of OGT 1757:1777 RESULTS Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2-ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2-ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2-ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2-ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. 36916376 10 243 dep decreased 3351:3359 arg1 1.46±0.16 3382:3390 1.46±0.16 3382:3390 1.46±0.16 3382:3390 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 10 243 dep decreased 3351:3359 arg1 3.55±0.87 3396:3404 3.55±0.87 3396:3404 3.55±0.87 3396:3404 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 5 244 theme protein 1549:1555 arg1 kinase 1557:1562 p38 mitogen-activated protein kinase 1527:1562 p38 mitogen-activated protein kinase (p38MAPK) 1527:1572 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 5 244 theme protein 1549:1555 arg1 p38MAPK 1565:1571 p38MAPK 1565:1571 p38MAPK 1565:1571 The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. 36916376 10 245 theme PP2+LPS 3318:3324 arg1 group 3326:3330 the PP2+LPS group 3314:3330 the PP2+LPS group 3314:3330 Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2-ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2-ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2-ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. 36916376 7 246 from ERK 2422:2424 arg1 cells 2476:2480 the endothelial cells 2460:2480 the endothelial cells of the OGT-OE+LPS group 2460:2504 Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2-ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2-ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2-ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2-ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. 36626982 0 0 theme mammalian 68:76 arg1 cells 78:82 mammalian cells 68:82 mammalian cells 68:82 Polo-like kinase 1 (PLK1) O-GlcNAcylation is essential for dividing mammalian cells and inhibits uterine carcinoma. 36626982 11 1 theme xenograft 1330:1338 arg1 models 1340:1345 mouse xenograft models 1324:1345 mouse xenograft models 1324:1345 In mouse xenograft models, we demonstrate that the O-GlcNAc-deficient PLK1-T291A and -T291N mutants enhance uterine carcinoma in animals. 36626982 4 2 theme mitotic 659:665 arg1 exit 667:670 mitotic exit 659:670 mitotic exit 659:670 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 10 3 theme H2B-GFP 1172:1178 arg1 cells 1180:1184 stable H2B-GFP cells 1165:1184 stable H2B-GFP cells 1165:1184 Using stable H2B-GFP cells, we found that PLK1-T291A and -T291N mutants display chromosome segregation defects, and result in misaligned and lagging chromosomes. 36626982 6 4 theme dissociation 799:810 arg1 MS 840:841 MS 840:841 MS 840:841 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 6 4 theme dissociation 799:810 arg1 spectrometry 826:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry 746:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS) 746:842 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 10 5 theme PLK1-T291A 1201:1210 arg1 mutants 1223:1229 PLK1-T291A and -T291N mutants 1201:1229 PLK1-T291A and -T291N mutants 1201:1229 Using stable H2B-GFP cells, we found that PLK1-T291A and -T291N mutants display chromosome segregation defects, and result in misaligned and lagging chromosomes. 36626982 10 6 theme stable 1165:1170 arg1 cells 1180:1184 stable H2B-GFP cells 1165:1184 stable H2B-GFP cells 1165:1184 Using stable H2B-GFP cells, we found that PLK1-T291A and -T291N mutants display chromosome segregation defects, and result in misaligned and lagging chromosomes. 36626982 6 7 theme peptide 856:862 arg1 fragment 864:871 a peptide fragment 854:871 a peptide fragment of PLK1 that is modified by O-GlcNAc 854:908 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 6 8 theme collisional 787:797 arg1 MS 840:841 MS 840:841 MS 840:841 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 6 8 theme collisional 787:797 arg1 spectrometry 826:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry 746:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS) 746:842 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 2 9 theme physiological 304:316 arg1 processes 318:326 numerous physiological processes 295:326 numerous physiological processes 295:326 O-GlcNAcylation occurs on Ser/Thr residues and is important for numerous physiological processes. 36626982 12 10 theme mitotic 1507:1513 arg1 function 1515:1522 its mitotic function 1503:1522 its mitotic function 1503:1522 Hence, we propose that OGT partially exerts its mitotic function through O-GlcNAcylation of PLK1, which might be one mechanism by which elevated levels of O-GlcNAc promote tumorigenesis. 36626982 11 11 theme O-GlcNAc-deficient 1372:1389 arg1 PLK1-T291A 1391:1400 O-GlcNAc-deficient PLK1-T291A 1372:1400 O-GlcNAc-deficient PLK1-T291A 1372:1400 In mouse xenograft models, we demonstrate that the O-GlcNAc-deficient PLK1-T291A and -T291N mutants enhance uterine carcinoma in animals. 36626982 6 12 theme energy/higher-energy 766:785 arg1 MS 840:841 MS 840:841 MS 840:841 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 6 12 theme energy/higher-energy 766:785 arg1 spectrometry 826:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry 746:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS) 746:842 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 2 13 theme numerous 295:302 arg1 processes 318:326 numerous physiological processes 295:326 numerous physiological processes 295:326 O-GlcNAcylation occurs on Ser/Thr residues and is important for numerous physiological processes. 36626982 10 14 theme segregation 1250:1260 arg1 defects 1262:1268 chromosome segregation defects 1239:1268 chromosome segregation defects 1239:1268 Using stable H2B-GFP cells, we found that PLK1-T291A and -T291N mutants display chromosome segregation defects, and result in misaligned and lagging chromosomes. 36626982 0 15 theme uterine 97:103 arg1 carcinoma 105:113 uterine carcinoma 97:113 uterine carcinoma 97:113 Polo-like kinase 1 (PLK1) O-GlcNAcylation is essential for dividing mammalian cells and inhibits uterine carcinoma. 36626982 11 16 theme -T291N 1406:1411 arg1 mutants 1413:1419 the O-GlcNAc-deficient PLK1-T291A and -T291N mutants 1368:1419 the O-GlcNAc-deficient PLK1-T291A and -T291N mutants 1368:1419 In mouse xenograft models, we demonstrate that the O-GlcNAc-deficient PLK1-T291A and -T291N mutants enhance uterine carcinoma in animals. 36626982 6 17 theme collisional 754:764 arg1 MS 840:841 MS 840:841 MS 840:841 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 6 17 theme collisional 754:764 arg1 spectrometry 826:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry 746:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS) 746:842 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 10 18 theme chromosome 1239:1248 arg1 defects 1262:1268 chromosome segregation defects 1239:1268 chromosome segregation defects 1239:1268 Using stable H2B-GFP cells, we found that PLK1-T291A and -T291N mutants display chromosome segregation defects, and result in misaligned and lagging chromosomes. 36626982 6 19 theme stepped 746:752 arg1 MS 840:841 MS 840:841 MS 840:841 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 6 19 theme stepped 746:752 arg1 spectrometry 826:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry 746:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS) 746:842 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 0 20 theme Polo-like 0:8 arg1 kinase 10:15 Polo-like kinase 1 0:17 Polo-like kinase 1 (PLK1) O-GlcNAcylation 0:40 Polo-like kinase 1 (PLK1) O-GlcNAcylation is essential for dividing mammalian cells and inhibits uterine carcinoma. 36626982 0 20 theme Polo-like 0:8 arg1 PLK1 20:23 PLK1 20:23 PLK1 20:23 Polo-like kinase 1 (PLK1) O-GlcNAcylation is essential for dividing mammalian cells and inhibits uterine carcinoma. 36626982 11 21 theme PLK1-T291A 1391:1400 arg1 mutants 1413:1419 the O-GlcNAc-deficient PLK1-T291A and -T291N mutants 1368:1419 the O-GlcNAc-deficient PLK1-T291A and -T291N mutants 1368:1419 In mouse xenograft models, we demonstrate that the O-GlcNAc-deficient PLK1-T291A and -T291N mutants enhance uterine carcinoma in animals. 36626982 3 22 theme fundamental 437:447 arg1 substrates 449:458 its fundamental substrates 433:458 its fundamental substrates during cell division 433:479 OGT is essential for dividing mammalian cells, and is involved in many human diseases; however, many of its fundamental substrates during cell division remain unknown. 36626982 0 23 theme kinase 10:15 arg1 O-GlcNAcylation 26:40 Polo-like kinase 1 (PLK1) O-GlcNAcylation 0:40 Polo-like kinase 1 (PLK1) O-GlcNAcylation 0:40 Polo-like kinase 1 (PLK1) O-GlcNAcylation is essential for dividing mammalian cells and inhibits uterine carcinoma. 36626982 4 24 theme chromosome 631:640 arg1 segregation 642:652 chromosome segregation 631:652 chromosome segregation 631:652 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 3 25 theme human 400:404 arg1 diseases 406:413 many human diseases 395:413 many human diseases 395:413 OGT is essential for dividing mammalian cells, and is involved in many human diseases; however, many of its fundamental substrates during cell division remain unknown. 36626982 8 26 from mutant 1044:1049 arg1 database 1063:1070 the TCGA database 1054:1070 the TCGA database 1054:1070 Interestingly, T291N is a uterine carcinoma mutant in the TCGA database. 36626982 12 27 theme elevated 1595:1602 arg1 levels 1604:1609 elevated levels 1595:1609 elevated levels of O-GlcNAc 1595:1621 Hence, we propose that OGT partially exerts its mitotic function through O-GlcNAcylation of PLK1, which might be one mechanism by which elevated levels of O-GlcNAc promote tumorigenesis. 36626982 4 28 theme polo-like 535:543 arg1 kinase 545:550 polo-like kinase 1 535:552 polo-like kinase 1 (PLK1) 535:559 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 4 28 theme polo-like 535:543 arg1 PLK1 555:558 PLK1 555:558 PLK1 555:558 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 4 28 theme polo-like 535:543 arg1 kinase 579:584 a mitotic master kinase 562:584 a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit 562:670 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 8 29 theme carcinoma 1034:1042 arg1 mutant 1044:1049 a uterine carcinoma mutant 1024:1049 a uterine carcinoma mutant in the TCGA database 1024:1070 Interestingly, T291N is a uterine carcinoma mutant in the TCGA database. 36626982 8 29 theme carcinoma 1034:1042 arg1 T291N 1015:1019 T291N 1015:1019 T291N 1015:1019 Interestingly, T291N is a uterine carcinoma mutant in the TCGA database. 36626982 7 30 theme Further 911:917 arg1 analysis 928:935 Further mutation analysis 911:935 Further mutation analysis of PLK1 911:943 Further mutation analysis of PLK1 shows that the T291A mutant decreases O-GlcNAcylation. 36626982 4 31 theme DNA 599:601 arg1 replication 603:613 DNA replication 599:613 DNA replication 599:613 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 8 32 theme uterine 1026:1032 arg1 mutant 1044:1049 a uterine carcinoma mutant 1024:1049 a uterine carcinoma mutant in the TCGA database 1024:1070 Interestingly, T291N is a uterine carcinoma mutant in the TCGA database. 36626982 8 32 theme uterine 1026:1032 arg1 T291N 1015:1019 T291N 1015:1019 T291N 1015:1019 Interestingly, T291N is a uterine carcinoma mutant in the TCGA database. 36626982 9 33 theme PLK1 1143:1146 arg1 stability 1148:1156 PLK1 stability 1143:1156 PLK1 stability 1143:1156 Our biochemical assays demonstrate that T291A and T291N both increase PLK1 stability. 36626982 1 34 theme intracellular 187:199 arg1 modification 217:228 intracellular O-GlcNAcylation modification 187:228 intracellular O-GlcNAcylation modification 187:228 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates intracellular O-GlcNAcylation modification. 36626982 11 35 theme uterine 1429:1435 arg1 carcinoma 1437:1445 uterine carcinoma 1429:1445 uterine carcinoma 1429:1445 In mouse xenograft models, we demonstrate that the O-GlcNAc-deficient PLK1-T291A and -T291N mutants enhance uterine carcinoma in animals. 36626982 12 36 theme O-GlcNAc 1614:1621 arg1 levels 1604:1609 elevated levels 1595:1609 elevated levels of O-GlcNAc 1595:1621 Hence, we propose that OGT partially exerts its mitotic function through O-GlcNAcylation of PLK1, which might be one mechanism by which elevated levels of O-GlcNAc promote tumorigenesis. 36626982 3 37 theme substrates 449:458 arg1 many 425:428 many 425:428 many 425:428 OGT is essential for dividing mammalian cells, and is involved in many human diseases; however, many of its fundamental substrates during cell division remain unknown. 36626982 3 37 theme substrates 449:458 arg1 substrates 449:458 its fundamental substrates 433:458 its fundamental substrates during cell division 433:479 OGT is essential for dividing mammalian cells, and is involved in many human diseases; however, many of its fundamental substrates during cell division remain unknown. 36626982 6 38 mod modified 889:896 arg1 fragment 864:871 a peptide fragment 854:871 a peptide fragment of PLK1 that is modified by O-GlcNAc 854:908 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 6 38 mod modified 889:896 arg3 O-GlcNAc 901:908 O-GlcNAc 901:908 O-GlcNAc 901:908 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 9 39 dep T291A 1113:1117 arg1 both 1129:1132 both 1129:1132 both 1129:1132 Our biochemical assays demonstrate that T291A and T291N both increase PLK1 stability. 36626982 1 40 theme O-GlcNAcylation 201:215 arg1 modification 217:228 intracellular O-GlcNAcylation modification 187:228 intracellular O-GlcNAcylation modification 187:228 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates intracellular O-GlcNAcylation modification. 36626982 11 41 theme mouse 1324:1328 arg1 models 1340:1345 mouse xenograft models 1324:1345 mouse xenograft models 1324:1345 In mouse xenograft models, we demonstrate that the O-GlcNAc-deficient PLK1-T291A and -T291N mutants enhance uterine carcinoma in animals. 36626982 7 42 theme T291A 960:964 arg1 mutant 966:971 the T291A mutant 956:971 the T291A mutant 956:971 Further mutation analysis of PLK1 shows that the T291A mutant decreases O-GlcNAcylation. 36626982 12 43 theme PLK1 1551:1554 arg1 O-GlcNAcylation 1532:1546 O-GlcNAcylation 1532:1546 O-GlcNAcylation 1532:1546 Hence, we propose that OGT partially exerts its mitotic function through O-GlcNAcylation of PLK1, which might be one mechanism by which elevated levels of O-GlcNAc promote tumorigenesis. 36626982 8 44 theme TCGA 1058:1061 arg1 database 1063:1070 the TCGA database 1054:1070 the TCGA database 1054:1070 Interestingly, T291N is a uterine carcinoma mutant in the TCGA database. 36626982 9 45 theme biochemical 1077:1087 arg1 assays 1089:1094 Our biochemical assays 1073:1094 Our biochemical assays 1073:1094 Our biochemical assays demonstrate that T291A and T291N both increase PLK1 stability. 36626982 4 46 from effect 518:523 arg1 kinase 545:550 polo-like kinase 1 535:552 polo-like kinase 1 (PLK1) 535:559 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 4 46 from effect 518:523 arg1 PLK1 555:558 PLK1 555:558 PLK1 555:558 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 4 46 from effect 518:523 arg1 kinase 579:584 a mitotic master kinase 562:584 a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit 562:670 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 1 47 link O-linked 120:127 arg1 O-GlcNAc 150:157 O-GlcNAc 150:157 O-GlcNAc 150:157 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates intracellular O-GlcNAcylation modification. 36626982 1 47 link O-linked 120:127 arg1 N-acetylglucosamine 129:147 O-linked N-acetylglucosamine 120:147 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 116:176 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates intracellular O-GlcNAcylation modification. 36626982 6 48 theme mass 821:824 arg1 MS 840:841 MS 840:841 MS 840:841 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 6 48 theme mass 821:824 arg1 spectrometry 826:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry 746:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS) 746:842 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 10 49 theme misaligned 1285:1294 arg1 chromosomes 1308:1318 misaligned and lagging chromosomes 1285:1318 chromosomes 1308:1318 Using stable H2B-GFP cells, we found that PLK1-T291A and -T291N mutants display chromosome segregation defects, and result in misaligned and lagging chromosomes. 36626982 4 50 theme OGT 528:530 arg1 effect 518:523 the effect 514:523 the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit 514:670 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 7 51 theme mutation 919:926 arg1 analysis 928:935 Further mutation analysis 911:935 Further mutation analysis of PLK1 911:943 Further mutation analysis of PLK1 shows that the T291A mutant decreases O-GlcNAcylation. 36626982 4 52 theme master 572:577 arg1 kinase 545:550 polo-like kinase 1 535:552 polo-like kinase 1 (PLK1) 535:559 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 4 52 theme master 572:577 arg1 kinase 579:584 a mitotic master kinase 562:584 a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit 562:670 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 6 53 theme sceHCD 813:818 arg1 MS 840:841 MS 840:841 MS 840:841 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 6 53 theme sceHCD 813:818 arg1 spectrometry 826:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry 746:837 stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS) 746:842 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 10 54 theme lagging 1300:1306 arg1 chromosomes 1308:1318 misaligned and lagging chromosomes 1285:1318 chromosomes 1308:1318 Using stable H2B-GFP cells, we found that PLK1-T291A and -T291N mutants display chromosome segregation defects, and result in misaligned and lagging chromosomes. 36626982 7 55 theme PLK1 940:943 arg1 analysis 928:935 Further mutation analysis 911:935 Further mutation analysis of PLK1 911:943 Further mutation analysis of PLK1 shows that the T291A mutant decreases O-GlcNAcylation. 36626982 1 56 theme O-linked 120:127 arg1 O-GlcNAc 150:157 O-GlcNAc 150:157 O-GlcNAc 150:157 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates intracellular O-GlcNAcylation modification. 36626982 1 56 theme O-linked 120:127 arg1 N-acetylglucosamine 129:147 O-linked N-acetylglucosamine 120:147 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 116:176 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates intracellular O-GlcNAcylation modification. 36626982 4 57 theme mitotic 564:570 arg1 kinase 545:550 polo-like kinase 1 535:552 polo-like kinase 1 (PLK1) 535:559 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 4 57 theme mitotic 564:570 arg1 kinase 579:584 a mitotic master kinase 562:584 a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit 562:670 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 3 58 theme cell 467:470 arg1 division 472:479 cell division 467:479 cell division 467:479 OGT is essential for dividing mammalian cells, and is involved in many human diseases; however, many of its fundamental substrates during cell division remain unknown. 36626982 1 59 theme N-acetylglucosamine 129:147 arg1 OGT 173:175 OGT 173:175 OGT 173:175 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates intracellular O-GlcNAcylation modification. 36626982 1 59 theme N-acetylglucosamine 129:147 arg1 transferase 160:170 The O-linked N-acetylglucosamine (O-GlcNAc) transferase 116:170 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) 116:176 The O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates intracellular O-GlcNAcylation modification. 36626982 4 60 theme mitotic 616:622 arg1 entry 624:628 mitotic entry 616:628 mitotic entry 616:628 Here we focus on the effect of OGT on polo-like kinase 1 (PLK1), a mitotic master kinase that governs DNA replication, mitotic entry, chromosome segregation, and mitotic exit. 36626982 3 61 theme mammalian 359:367 arg1 cells 369:373 mammalian cells 359:373 mammalian cells 359:373 OGT is essential for dividing mammalian cells, and is involved in many human diseases; however, many of its fundamental substrates during cell division remain unknown. 36626982 6 62 theme PLK1 876:879 arg1 fragment 864:871 a peptide fragment 854:871 a peptide fragment of PLK1 that is modified by O-GlcNAc 854:908 By utilizing stepped collisional energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (MS), we found a peptide fragment of PLK1 that is modified by O-GlcNAc. 36626982 2 63 theme Ser/Thr 257:263 arg1 residues 265:272 Ser/Thr residues 257:272 Ser/Thr residues 257:272 O-GlcNAcylation occurs on Ser/Thr residues and is important for numerous physiological processes. 36626982 3 64 theme many 395:398 arg1 diseases 406:413 many human diseases 395:413 many human diseases 395:413 OGT is essential for dividing mammalian cells, and is involved in many human diseases; however, many of its fundamental substrates during cell division remain unknown. 36626982 10 65 theme -T291N 1216:1221 arg1 mutants 1223:1229 PLK1-T291A and -T291N mutants 1201:1229 PLK1-T291A and -T291N mutants 1201:1229 Using stable H2B-GFP cells, we found that PLK1-T291A and -T291N mutants display chromosome segregation defects, and result in misaligned and lagging chromosomes. 36112613 6 0 theme O-linked 1245:1252 arg1 O-GlcNAc 1276:1283 O-GlcNAc 1276:1283 O-GlcNAc 1276:1283 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 6 0 theme O-linked 1245:1252 arg1 glucosamine 1263:1273 the O-linked N-acetyl glucosamine 1241:1273 the O-linked N-acetyl glucosamine (O-GlcNAc) pathway 1241:1292 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 2 1 theme even 342:345 arg1 outputs 356:362 distinct or even opposite outputs 330:362 distinct or even opposite outputs 330:362 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 7 2 theme energy 1436:1441 arg1 sensing 1443:1449 energy sensing 1436:1449 energy sensing 1436:1449 Although ARD maintenance was not significantly influenced by the nutrient sensors in our screen, we found that ARD recovery was modulated by energy sensing, stress response, insulin-like signaling, and the TOR pathway. 36112613 6 3 theme ARD 1167:1169 arg1 initiation 1171:1180 ARD initiation 1167:1180 ARD initiation 1167:1180 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 8 4 theme ARD 1612:1614 arg1 initiation 1616:1625 ARD initiation 1612:1625 ARD initiation 1612:1625 Further investigation of downstream targets of NHR-49 suggest the transcription factor influences ARD initiation through the fatty acid β-oxidation pathway. 36112613 2 5 theme nutrient 251:258 arg1 intake 260:265 nutrient intake 251:265 nutrient intake 251:265 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 6 6 link O-linked 1245:1252 arg1 O-GlcNAc 1276:1283 O-GlcNAc 1276:1283 O-GlcNAc 1276:1283 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 6 6 link O-linked 1245:1252 arg1 glucosamine 1263:1273 the O-linked N-acetyl glucosamine 1241:1273 the O-linked N-acetyl glucosamine (O-GlcNAc) pathway 1241:1292 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 3 7 theme pathways 545:552 arg1 diversity 562:570 the diversity 558:570 the diversity in outputs 558:581 Due to the complexity of metabolic pathways and the diversity in outputs, the underlying mechanisms regulating diet-associated pro-longevity are not yet well understood. 36112613 3 7 theme pathways 545:552 arg1 complexity 521:530 the complexity 517:530 the complexity of metabolic pathways 517:552 Due to the complexity of metabolic pathways and the diversity in outputs, the underlying mechanisms regulating diet-associated pro-longevity are not yet well understood. 36112613 2 8 from nature 474:479 arg1 nutrients 499:507 nutrients 499:507 nutrients 499:507 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 6 9 theme acid 1204:1207 arg1 metabolism 1209:1218 fatty acid metabolism 1198:1218 fatty acid metabolism 1198:1218 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 5 10 theme greater 914:920 arg1 depth 922:926 greater depth 914:926 greater depth 914:926 To explore the metabolic pathways regulating ARD in greater depth, we performed a candidate-based genetic screen analyzing select nutrient-sensing pathways to determine their contribution to the regulation of ARD. 36112613 7 11 from sensors 1369:1375 arg1 screen 1384:1389 our screen 1380:1389 our screen 1380:1389 Although ARD maintenance was not significantly influenced by the nutrient sensors in our screen, we found that ARD recovery was modulated by energy sensing, stress response, insulin-like signaling, and the TOR pathway. 36112613 6 12 theme glucosamine 1263:1273 arg1 pathway 1286:1292 the O-linked N-acetyl glucosamine (O-GlcNAc) pathway 1241:1292 the O-linked N-acetyl glucosamine (O-GlcNAc) pathway 1241:1292 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 5 13 theme ARD 1071:1073 arg1 regulation 1057:1066 the regulation 1053:1066 the regulation of ARD 1053:1073 To explore the metabolic pathways regulating ARD in greater depth, we performed a candidate-based genetic screen analyzing select nutrient-sensing pathways to determine their contribution to the regulation of ARD. 36112613 3 14 theme underlying 588:597 arg1 mechanisms 599:608 the underlying mechanisms 584:608 the underlying mechanisms regulating diet-associated pro-longevity 584:649 Due to the complexity of metabolic pathways and the diversity in outputs, the underlying mechanisms regulating diet-associated pro-longevity are not yet well understood. 36112613 4 15 theme reproductive 686:697 arg1 model 784:788 a dietary restriction model 762:788 a dietary restriction model that is associated with lengthened lifespan and reproductive potential 762:859 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 4 15 theme reproductive 686:697 arg1 ARD 709:711 ARD 709:711 ARD 709:711 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 4 15 theme reproductive 686:697 arg1 diapause 699:706 Adult reproductive diapause 680:706 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans 680:757 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 2 16 theme changes 488:494 arg1 nature 474:479 the nature 470:479 the nature of the changes in nutrients 470:507 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 2 16 theme changes 488:494 arg1 lifecycle 441:449 the lifecycle 437:449 the lifecycle of the organism 437:465 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 0 17 from diapause 56:63 arg1 elegans 71:77 C. elegans 68:77 C. elegans 68:77 Nutrient sensing pathways regulating adult reproductive diapause in C. elegans. 36112613 5 18 theme select 985:990 arg1 pathways 1009:1016 select nutrient-sensing pathways 985:1016 select nutrient-sensing pathways 985:1016 To explore the metabolic pathways regulating ARD in greater depth, we performed a candidate-based genetic screen analyzing select nutrient-sensing pathways to determine their contribution to the regulation of ARD. 36112613 7 19 theme ARD 1304:1306 arg1 maintenance 1308:1318 ARD maintenance 1304:1318 ARD maintenance 1304:1318 Although ARD maintenance was not significantly influenced by the nutrient sensors in our screen, we found that ARD recovery was modulated by energy sensing, stress response, insulin-like signaling, and the TOR pathway. 36112613 2 20 theme several 377:383 arg1 factors 385:391 several factors 377:391 several factors 377:391 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 0 21 theme Nutrient 0:7 arg1 pathways 17:24 Nutrient sensing pathways 0:24 Nutrient sensing pathways 0:24 Nutrient sensing pathways regulating adult reproductive diapause in C. elegans. 36112613 1 22 theme environmental 92:104 arg1 restriction 137:147 dietary restriction 129:147 dietary restriction 129:147 Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. 36112613 1 22 theme environmental 92:104 arg1 manipulations 106:118 Genetic and environmental manipulations 80:118 Genetic and environmental manipulations 80:118 Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. 36112613 9 23 theme entry 1782:1786 arg1 defects 1788:1794 ARD entry defects 1778:1794 ARD entry defects 1778:1794 Consistent with these findings, our analysis revealed a change in levels of neutral lipids associated with ARD entry defects. 36112613 4 24 theme organism 727:734 arg1 elegans 751:757 the model organism Caenorhabditis elegans 717:757 the model organism Caenorhabditis elegans 717:757 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 2 25 theme dietary 407:413 arg1 restriction 415:425 dietary restriction 407:425 dietary restriction 407:425 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 5 26 theme candidate-based 944:958 arg1 screen 968:973 a candidate-based genetic screen 942:973 a candidate-based genetic screen 942:973 To explore the metabolic pathways regulating ARD in greater depth, we performed a candidate-based genetic screen analyzing select nutrient-sensing pathways to determine their contribution to the regulation of ARD. 36112613 2 27 theme organism 458:465 arg1 nature 474:479 the nature 470:479 the nature of the changes in nutrients 470:507 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 2 27 theme organism 458:465 arg1 lifecycle 441:449 the lifecycle 437:449 the lifecycle of the organism 437:465 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 9 28 with Consistent 1671:1680 arg1 findings 1693:1700 these findings 1687:1700 these findings 1687:1700 Consistent with these findings, our analysis revealed a change in levels of neutral lipids associated with ARD entry defects. 36112613 0 29 theme adult 37:41 arg1 diapause 56:63 adult reproductive diapause 37:63 adult reproductive diapause in C. elegans 37:77 Nutrient sensing pathways regulating adult reproductive diapause in C. elegans. 36112613 10 30 theme conserved 1819:1827 arg1 pathways 1837:1844 conserved genetic pathways 1819:1844 conserved genetic pathways required for ARD entry and recovery 1819:1880 Our findings identify conserved genetic pathways required for ARD entry and recovery and uncover genetic interactions that provide insight into the role of OGT and OGA. 36112613 4 31 theme lengthened 814:823 arg1 potential 851:859 lengthened lifespan and reproductive potential 814:859 lengthened lifespan and reproductive potential 814:859 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 8 32 theme downstream 1539:1548 arg1 targets 1550:1556 downstream targets 1539:1556 downstream targets of NHR-49 1539:1566 Further investigation of downstream targets of NHR-49 suggest the transcription factor influences ARD initiation through the fatty acid β-oxidation pathway. 36112613 4 33 theme restriction 772:782 arg1 model 784:788 a dietary restriction model 762:788 a dietary restriction model that is associated with lengthened lifespan and reproductive potential 762:859 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 4 33 theme restriction 772:782 arg1 diapause 699:706 Adult reproductive diapause 680:706 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans 680:757 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 7 34 theme stress 1452:1457 arg1 response 1459:1466 stress response 1452:1466 stress response 1452:1466 Although ARD maintenance was not significantly influenced by the nutrient sensors in our screen, we found that ARD recovery was modulated by energy sensing, stress response, insulin-like signaling, and the TOR pathway. 36112613 4 35 from diapause 699:706 arg1 elegans 751:757 the model organism Caenorhabditis elegans 717:757 the model organism Caenorhabditis elegans 717:757 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 6 36 theme ARD 1108:1110 arg1 phases 1098:1103 the three phases 1088:1103 the three phases of ARD 1088:1110 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 6 37 theme N-acetyl 1254:1261 arg1 O-GlcNAc 1276:1283 O-GlcNAc 1276:1283 O-GlcNAc 1276:1283 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 6 37 theme N-acetyl 1254:1261 arg1 glucosamine 1263:1273 the O-linked N-acetyl glucosamine 1241:1273 the O-linked N-acetyl glucosamine (O-GlcNAc) pathway 1241:1292 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 2 38 theme opposite 347:354 arg1 outputs 356:362 distinct or even opposite outputs 330:362 distinct or even opposite outputs 330:362 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 8 39 theme acid 1645:1648 arg1 pathway 1662:1668 the fatty acid β-oxidation pathway 1635:1668 the fatty acid β-oxidation pathway 1635:1668 Further investigation of downstream targets of NHR-49 suggest the transcription factor influences ARD initiation through the fatty acid β-oxidation pathway. 36112613 8 40 theme transcription 1580:1592 arg1 factor 1594:1599 the transcription factor 1576:1599 the transcription factor 1576:1599 Further investigation of downstream targets of NHR-49 suggest the transcription factor influences ARD initiation through the fatty acid β-oxidation pathway. 36112613 1 41 theme health 167:172 arg1 span 174:177 health span 167:177 health span 167:177 Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. 36112613 7 42 theme ARD 1406:1408 arg1 recovery 1410:1417 ARD recovery 1406:1417 ARD recovery 1406:1417 Although ARD maintenance was not significantly influenced by the nutrient sensors in our screen, we found that ARD recovery was modulated by energy sensing, stress response, insulin-like signaling, and the TOR pathway. 36112613 4 43 theme lifespan 825:832 arg1 potential 851:859 lengthened lifespan and reproductive potential 814:859 lengthened lifespan and reproductive potential 814:859 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 3 44 theme metabolic 535:543 arg1 pathways 545:552 metabolic pathways 535:552 metabolic pathways 535:552 Due to the complexity of metabolic pathways and the diversity in outputs, the underlying mechanisms regulating diet-associated pro-longevity are not yet well understood. 36112613 4 45 theme reproductive 838:849 arg1 potential 851:859 lengthened lifespan and reproductive potential 814:859 lengthened lifespan and reproductive potential 814:859 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 2 46 theme metabolic 293:301 arg1 pathways 303:310 metabolic pathways 293:310 metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients 293:507 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 2 47 dep trigger 267:273 arg1 overlapping 281:291 overlapping 281:291 trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients 267:507 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 1 48 theme wide 197:200 arg1 humans 232:237 humans 232:237 humans 232:237 Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. 36112613 1 48 theme wide 197:200 arg1 range 202:206 a wide range 195:206 a wide range of organisms, including humans 195:237 Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. 36112613 7 49 theme nutrient 1360:1367 arg1 sensors 1369:1375 the nutrient sensors 1356:1375 the nutrient sensors in our screen 1356:1389 Although ARD maintenance was not significantly influenced by the nutrient sensors in our screen, we found that ARD recovery was modulated by energy sensing, stress response, insulin-like signaling, and the TOR pathway. 36112613 10 50 theme OGA 1961:1963 arg1 role 1945:1948 the role 1941:1948 the role of OGT and OGA 1941:1963 Our findings identify conserved genetic pathways required for ARD entry and recovery and uncover genetic interactions that provide insight into the role of OGT and OGA. 36112613 2 51 from changes 488:494 arg1 nutrients 499:507 nutrients 499:507 nutrients 499:507 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 6 52 theme fatty 1198:1202 arg1 metabolism 1209:1218 fatty acid metabolism 1198:1218 fatty acid metabolism 1198:1218 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 3 53 from complexity 521:530 arg1 outputs 575:581 outputs 575:581 outputs 575:581 Due to the complexity of metabolic pathways and the diversity in outputs, the underlying mechanisms regulating diet-associated pro-longevity are not yet well understood. 36112613 10 54 theme OGT 1953:1955 arg1 role 1945:1948 the role 1941:1948 the role of OGT and OGA 1941:1963 Our findings identify conserved genetic pathways required for ARD entry and recovery and uncover genetic interactions that provide insight into the role of OGT and OGA. 36112613 1 55 theme dietary 129:135 arg1 restriction 137:147 dietary restriction 129:147 dietary restriction 129:147 Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. 36112613 2 56 from nutrients 499:507 arg1 nature 474:479 the nature 470:479 the nature of the changes in nutrients 470:507 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 2 56 from nutrients 499:507 arg1 lifecycle 441:449 the lifecycle 437:449 the lifecycle of the organism 437:465 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 5 57 theme metabolic 877:885 arg1 pathways 887:894 the metabolic pathways 873:894 the metabolic pathways regulating ARD in greater depth 873:926 To explore the metabolic pathways regulating ARD in greater depth, we performed a candidate-based genetic screen analyzing select nutrient-sensing pathways to determine their contribution to the regulation of ARD. 36112613 4 58 theme Adult 680:684 arg1 model 784:788 a dietary restriction model 762:788 a dietary restriction model that is associated with lengthened lifespan and reproductive potential 762:859 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 4 58 theme Adult 680:684 arg1 ARD 709:711 ARD 709:711 ARD 709:711 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 4 58 theme Adult 680:684 arg1 diapause 699:706 Adult reproductive diapause 680:706 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans 680:757 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 5 59 from ARD 907:909 arg1 depth 922:926 greater depth 914:926 greater depth 914:926 To explore the metabolic pathways regulating ARD in greater depth, we performed a candidate-based genetic screen analyzing select nutrient-sensing pathways to determine their contribution to the regulation of ARD. 36112613 5 60 theme genetic 960:966 arg1 screen 968:973 a candidate-based genetic screen 942:973 a candidate-based genetic screen 942:973 To explore the metabolic pathways regulating ARD in greater depth, we performed a candidate-based genetic screen analyzing select nutrient-sensing pathways to determine their contribution to the regulation of ARD. 36112613 7 61 theme TOR 1501:1503 arg1 pathway 1505:1511 the TOR pathway 1497:1511 the TOR pathway 1497:1511 Although ARD maintenance was not significantly influenced by the nutrient sensors in our screen, we found that ARD recovery was modulated by energy sensing, stress response, insulin-like signaling, and the TOR pathway. 36112613 9 62 theme neutral 1747:1753 arg1 lipids 1755:1760 neutral lipids 1747:1760 neutral lipids associated with ARD entry defects 1747:1794 Consistent with these findings, our analysis revealed a change in levels of neutral lipids associated with ARD entry defects. 36112613 4 63 theme Caenorhabditis 736:749 arg1 elegans 751:757 the model organism Caenorhabditis elegans 717:757 the model organism Caenorhabditis elegans 717:757 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 9 64 theme lipids 1755:1760 arg1 levels 1737:1742 levels 1737:1742 levels of neutral lipids associated with ARD entry defects 1737:1794 Consistent with these findings, our analysis revealed a change in levels of neutral lipids associated with ARD entry defects. 36112613 0 65 theme sensing 9:15 arg1 pathways 17:24 Nutrient sensing pathways 0:24 Nutrient sensing pathways 0:24 Nutrient sensing pathways regulating adult reproductive diapause in C. elegans. 36112613 2 66 from lifecycle 441:449 arg1 nutrients 499:507 nutrients 499:507 nutrients 499:507 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 9 67 theme ARD 1778:1780 arg1 defects 1788:1794 ARD entry defects 1778:1794 ARD entry defects 1778:1794 Consistent with these findings, our analysis revealed a change in levels of neutral lipids associated with ARD entry defects. 36112613 6 68 dep Focusing 1076:1083 arg1 maintenance 1125:1135 maintenance 1125:1135 maintenance 1125:1135 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 6 68 dep Focusing 1076:1083 arg1 recovery 1142:1149 recovery 1142:1149 recovery 1142:1149 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 6 68 dep Focusing 1076:1083 arg1 initiation 1113:1122 initiation 1113:1122 initiation 1113:1122 Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. 36112613 8 69 theme Further 1514:1520 arg1 investigation 1522:1534 Further investigation 1514:1534 Further investigation of downstream targets of NHR-49 1514:1566 Further investigation of downstream targets of NHR-49 suggest the transcription factor influences ARD initiation through the fatty acid β-oxidation pathway. 36112613 3 70 theme diet-associated 621:635 arg1 pro-longevity 637:649 diet-associated pro-longevity 621:649 diet-associated pro-longevity 621:649 Due to the complexity of metabolic pathways and the diversity in outputs, the underlying mechanisms regulating diet-associated pro-longevity are not yet well understood. 36112613 4 71 theme model 721:725 arg1 elegans 751:757 the model organism Caenorhabditis elegans 717:757 the model organism Caenorhabditis elegans 717:757 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 3 72 from diversity 562:570 arg1 outputs 575:581 outputs 575:581 outputs 575:581 Due to the complexity of metabolic pathways and the diversity in outputs, the underlying mechanisms regulating diet-associated pro-longevity are not yet well understood. 36112613 0 73 theme reproductive 43:54 arg1 diapause 56:63 adult reproductive diapause 37:63 adult reproductive diapause in C. elegans 37:77 Nutrient sensing pathways regulating adult reproductive diapause in C. elegans. 36112613 2 74 from Changes 240:246 arg1 intake 260:265 nutrient intake 251:265 nutrient intake 251:265 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 10 75 theme genetic 1829:1835 arg1 pathways 1837:1844 conserved genetic pathways 1819:1844 conserved genetic pathways required for ARD entry and recovery 1819:1880 Our findings identify conserved genetic pathways required for ARD entry and recovery and uncover genetic interactions that provide insight into the role of OGT and OGA. 36112613 8 76 theme targets 1550:1556 arg1 investigation 1522:1534 Further investigation 1514:1534 Further investigation of downstream targets of NHR-49 1514:1566 Further investigation of downstream targets of NHR-49 suggest the transcription factor influences ARD initiation through the fatty acid β-oxidation pathway. 36112613 2 77 theme distinct 330:337 arg1 outputs 356:362 distinct or even opposite outputs 330:362 distinct or even opposite outputs 330:362 Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. 36112613 7 78 theme insulin-like 1469:1480 arg1 signaling 1482:1490 insulin-like signaling 1469:1490 insulin-like signaling 1469:1490 Although ARD maintenance was not significantly influenced by the nutrient sensors in our screen, we found that ARD recovery was modulated by energy sensing, stress response, insulin-like signaling, and the TOR pathway. 36112613 5 79 theme nutrient-sensing 992:1007 arg1 pathways 1009:1016 select nutrient-sensing pathways 985:1016 select nutrient-sensing pathways 985:1016 To explore the metabolic pathways regulating ARD in greater depth, we performed a candidate-based genetic screen analyzing select nutrient-sensing pathways to determine their contribution to the regulation of ARD. 36112613 8 80 theme NHR-49 1561:1566 arg1 targets 1550:1556 downstream targets 1539:1556 downstream targets of NHR-49 1539:1566 Further investigation of downstream targets of NHR-49 suggest the transcription factor influences ARD initiation through the fatty acid β-oxidation pathway. 36112613 1 81 theme Genetic 80:86 arg1 restriction 137:147 dietary restriction 129:147 dietary restriction 129:147 Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. 36112613 1 81 theme Genetic 80:86 arg1 manipulations 106:118 Genetic and environmental manipulations 80:118 Genetic and environmental manipulations 80:118 Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. 36112613 10 82 theme ARD 1859:1861 arg1 entry 1863:1867 ARD entry 1859:1867 ARD entry 1859:1867 Our findings identify conserved genetic pathways required for ARD entry and recovery and uncover genetic interactions that provide insight into the role of OGT and OGA. 36112613 4 83 theme dietary 764:770 arg1 model 784:788 a dietary restriction model 762:788 a dietary restriction model that is associated with lengthened lifespan and reproductive potential 762:859 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 4 83 theme dietary 764:770 arg1 diapause 699:706 Adult reproductive diapause 680:706 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans 680:757 Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. 36112613 8 84 theme fatty 1639:1643 arg1 acid 1645:1648 fatty acid 1639:1648 the fatty acid β-oxidation pathway 1635:1668 Further investigation of downstream targets of NHR-49 suggest the transcription factor influences ARD initiation through the fatty acid β-oxidation pathway. 36112613 1 85 theme organisms 211:219 arg1 humans 232:237 humans 232:237 humans 232:237 Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. 36112613 1 85 theme organisms 211:219 arg1 range 202:206 a wide range 195:206 a wide range of organisms, including humans 195:237 Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. 36112613 9 86 from change 1727:1732 arg1 levels 1737:1742 levels 1737:1742 levels of neutral lipids associated with ARD entry defects 1737:1794 Consistent with these findings, our analysis revealed a change in levels of neutral lipids associated with ARD entry defects. 36112613 10 87 theme genetic 1894:1900 arg1 interactions 1902:1913 genetic interactions 1894:1913 genetic interactions that provide insight into the role of OGT and OGA 1894:1963 Our findings identify conserved genetic pathways required for ARD entry and recovery and uncover genetic interactions that provide insight into the role of OGT and OGA. 36112613 8 88 theme β-oxidation 1650:1660 arg1 pathway 1662:1668 the fatty acid β-oxidation pathway 1635:1668 the fatty acid β-oxidation pathway 1635:1668 Further investigation of downstream targets of NHR-49 suggest the transcription factor influences ARD initiation through the fatty acid β-oxidation pathway. 36031420 8 0 theme mouse 1786:1790 arg1 sensitivity 1792:1802 mouse sensitivity 1786:1802 mouse sensitivity to sevoflurane anaesthesia 1786:1829 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 1 1 from outcomes 215:222 arg1 patients 227:234 patients 227:234 patients 227:234 BACKGROUND Hypersensitivity to general anaesthetics predicts adverse postoperative outcomes in patients. 36031420 8 2 from modulation 1867:1876 arg1 brain 1918:1922 the brain 1914:1922 the brain 1914:1922 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 6 3 from elevation 1233:1241 arg1 thalamus 1335:1342 the thalamus 1331:1342 the thalamus 1331:1342 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 6 3 from elevation 1233:1241 arg1 brain 1310:1314 brain 1310:1314 brain 1310:1314 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 0 4 from O-GlcNAcylation 18:32 arg1 brain 41:45 the brain 37:45 the brain 37:45 Hypoxia-triggered O-GlcNAcylation in the brain drives the glutamate-glutamine cycle and reduces sensitivity to sevoflurane in mice. 36031420 4 5 theme underlying 899:908 arg1 mechanisms 910:919 the underlying mechanisms 895:919 the underlying mechanisms 895:919 Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms. 36031420 3 6 theme effective 538:546 arg1 concentrations 548:561 the effective concentrations 534:561 the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) 534:680 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 8 7 theme Intermittent 1746:1757 arg1 hypoxia 1759:1765 Intermittent hypoxia 1746:1765 Intermittent hypoxia exposure 1746:1774 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 3 8 dep hypoxia 451:457 arg1 % 469:469 oxygen 10% 460:469 oxygen 10% for 8 h day-1 460:483 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 2 9 theme sevoflurane 339:349 arg1 sensitivity 351:361 sevoflurane sensitivity 339:361 sevoflurane sensitivity 339:361 Hypoxia exerts extensive pathophysiological effects on the brain; however, whether hypoxia influences sevoflurane sensitivity and its underlying mechanisms remain poorly understood. 36031420 6 10 from reduction 1176:1184 arg1 sensitivity 1201:1211 sevoflurane sensitivity 1189:1211 sevoflurane sensitivity 1189:1211 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 5 11 theme mice 986:989 arg1 % 1132:1132 the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% 963:1132 the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% 963:1132 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 6 12 theme O-linked 1254:1261 arg1 N-acetylglucosamine 1263:1281 protein O-linked N-acetylglucosamine 1246:1281 protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain 1246:1314 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 6 12 theme O-linked 1254:1261 arg1 O-GlcNAc 1284:1291 O-GlcNAc 1284:1291 O-GlcNAc 1284:1291 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 5 13 theme sevoflurane 1025:1035 arg1 LTWR 1057:1060 LTWR 1057:1060 LTWR 1057:1060 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 5 13 theme sevoflurane 1025:1035 arg1 concentrations 1007:1020 higher concentrations 1000:1020 higher concentrations of sevoflurane to present LORR 1000:1051 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 5 14 theme hypoxia-acclimated 967:984 arg1 mice 986:989 the hypoxia-acclimated mice 963:989 the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% 963:1132 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 8 15 theme glutamate-glutamine 1885:1903 arg1 cycle 1905:1909 the glutamate-glutamine cycle 1881:1909 the glutamate-glutamine cycle in the brain 1881:1922 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 3 16 with anaesthetised 502:514 arg1 sevoflurane 521:531 sevoflurane 521:531 sevoflurane 521:531 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 7 17 theme glutamine 1583:1591 arg1 synthesis 1570:1578 de novo synthesis 1562:1578 de novo synthesis of glutamine from glucose 1562:1604 Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase. 36031420 5 18 dep group 956:960 arg1 % 1148:1148 2.22 [0.06]% 1137:1148 2.22 [0.06]% 1137:1148 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 5 18 dep group 956:960 arg1 % 1132:1132 the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% 963:1132 the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% 963:1132 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 6 19 link O-linked 1254:1261 arg1 N-acetylglucosamine 1263:1281 protein O-linked N-acetylglucosamine 1246:1281 protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain 1246:1314 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 6 19 link O-linked 1254:1261 arg1 O-GlcNAc 1284:1291 O-GlcNAc 1284:1291 O-GlcNAc 1284:1291 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 1 20 theme postoperative 201:213 arg1 outcomes 215:222 adverse postoperative outcomes 193:222 adverse postoperative outcomes in patients 193:234 BACKGROUND Hypersensitivity to general anaesthetics predicts adverse postoperative outcomes in patients. 36031420 3 21 theme METHODS 419:425 arg1 Mice 427:430 METHODS Mice 419:430 METHODS Mice 419:430 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 5 22 theme control 948:954 arg1 group 956:960 the control group 944:960 the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01) 944:1157 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 4 23 theme carbon-13 787:795 arg1 tracing 797:803 carbon-13 tracing 787:803 carbon-13 tracing 787:803 Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms. 36031420 7 24 theme synthetase 1722:1731 arg1 activation 1698:1707 activation 1698:1707 activation of glutamine synthetase 1698:1731 Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase. 36031420 7 24 theme synthetase 1722:1731 arg1 flux 1689:1692 glycolytic flux 1678:1692 glycolytic flux 1678:1692 Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase. 36031420 7 25 theme glycolytic 1678:1687 arg1 flux 1689:1692 glycolytic flux 1678:1692 glycolytic flux 1678:1692 Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase. 36031420 2 26 theme underlying 371:380 arg1 mechanisms 382:391 its underlying mechanisms 367:391 its underlying mechanisms 367:391 Hypoxia exerts extensive pathophysiological effects on the brain; however, whether hypoxia influences sevoflurane sensitivity and its underlying mechanisms remain poorly understood. 36031420 3 27 theme 8 475:475 arg1 h 477:477 h 477:477 h 477:477 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 0 28 theme Hypoxia-triggered 0:16 arg1 O-GlcNAcylation 18:32 Hypoxia-triggered O-GlcNAcylation 0:32 Hypoxia-triggered O-GlcNAcylation in the brain 0:45 Hypoxia-triggered O-GlcNAcylation in the brain drives the glutamate-glutamine cycle and reduces sensitivity to sevoflurane in mice. 36031420 6 29 theme Hypoxia-induced 1160:1174 arg1 reduction 1176:1184 Hypoxia-induced reduction 1160:1184 Hypoxia-induced reduction in sevoflurane sensitivity 1160:1211 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 6 30 theme protein 1246:1252 arg1 N-acetylglucosamine 1263:1281 protein O-linked N-acetylglucosamine 1246:1281 protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain 1246:1314 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 6 30 theme protein 1246:1252 arg1 O-GlcNAc 1284:1291 O-GlcNAc 1284:1291 O-GlcNAc 1284:1291 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 3 31 theme h 477:477 arg1 day-1 479:483 8 h day-1 475:483 8 h day-1 475:483 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 5 32 dep % 1132:1132 arg1 P<0.01 1151:1156 P<0.01 1151:1156 P<0.01 1151:1156 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 6 33 theme sevoflurane 1189:1199 arg1 sensitivity 1201:1211 sevoflurane sensitivity 1189:1211 sevoflurane sensitivity 1189:1211 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 3 34 theme animals 578:584 arg1 EC50 587:590 EC50 587:590 EC50 587:590 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 3 34 theme animals 578:584 arg1 % 569:569 50% 567:569 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) 567:680 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 3 34 theme animals 578:584 arg1 animals 578:584 the animals 574:584 the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) 574:680 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 7 35 theme glutamine 1712:1720 arg1 synthetase 1722:1731 glutamine synthetase 1712:1731 glutamine synthetase 1712:1731 Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase. 36031420 8 36 from cycle 1905:1909 arg1 brain 1918:1922 the brain 1914:1922 the brain 1914:1922 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 6 37 theme amidotransferase 1432:1447 arg1 inhibitor 1449:1457 a glutamine fructose-6-phosphate amidotransferase inhibitor 1399:1457 a glutamine fructose-6-phosphate amidotransferase inhibitor 1399:1457 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 6 37 theme amidotransferase 1432:1447 arg1 6-diazo-5-oxo-l-norleucine 1371:1396 6-diazo-5-oxo-l-norleucine 1371:1396 6-diazo-5-oxo-l-norleucine 1371:1396 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 0 38 from sensitivity 96:106 arg1 mice 126:129 mice 126:129 mice 126:129 Hypoxia-triggered O-GlcNAcylation in the brain drives the glutamate-glutamine cycle and reduces sensitivity to sevoflurane in mice. 36031420 1 39 theme adverse 193:199 arg1 outcomes 215:222 adverse postoperative outcomes 193:222 adverse postoperative outcomes in patients 193:234 BACKGROUND Hypersensitivity to general anaesthetics predicts adverse postoperative outcomes in patients. 36031420 6 40 theme fructose-6-phosphate 1411:1430 arg1 amidotransferase 1432:1447 glutamine fructose-6-phosphate amidotransferase 1401:1447 a glutamine fructose-6-phosphate amidotransferase inhibitor 1399:1457 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 4 41 theme Positron 699:706 arg1 tomography 737:746 Positron emission tomography-computed tomography 699:746 Positron emission tomography-computed tomography 699:746 Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms. 36031420 3 42 theme tail-pinch 644:653 arg1 response 666:673 tail-pinch withdrawal response 644:673 tail-pinch withdrawal response (LTWR) 644:680 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 3 42 theme tail-pinch 644:653 arg1 LTWR 676:679 LTWR 676:679 LTWR 676:679 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 4 43 theme electrophysiological 837:856 arg1 techniques 858:867 electrophysiological techniques 837:867 electrophysiological techniques 837:867 Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms. 36031420 8 44 theme sevoflurane 1807:1817 arg1 anaesthesia 1819:1829 sevoflurane anaesthesia 1807:1829 sevoflurane anaesthesia 1807:1829 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 6 45 theme glutamine 1401:1409 arg1 amidotransferase 1432:1447 glutamine fructose-6-phosphate amidotransferase 1401:1447 a glutamine fructose-6-phosphate amidotransferase inhibitor 1399:1457 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 6 46 from modification 1294:1305 arg1 brain 1310:1314 brain 1310:1314 brain 1310:1314 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 7 47 from glucose 1598:1604 arg1 synthesis 1570:1578 de novo synthesis 1562:1578 de novo synthesis of glutamine from glucose 1562:1604 Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase. 36031420 3 48 theme righting 609:616 arg1 LORR 626:629 LORR 626:629 LORR 626:629 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 3 48 theme righting 609:616 arg1 reflex 618:623 righting reflex 609:623 righting reflex (LORR) 609:630 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 8 49 theme enhanced 1839:1846 arg1 modulation 1867:1876 enhanced O-GlcNAc-dependent modulation 1839:1876 enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain 1839:1922 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 0 50 theme glutamate-glutamine 58:76 arg1 cycle 78:82 the glutamate-glutamine cycle 54:82 the glutamate-glutamine cycle 54:82 Hypoxia-triggered O-GlcNAcylation in the brain drives the glutamate-glutamine cycle and reduces sensitivity to sevoflurane in mice. 36031420 5 51 theme 2.22 1137:1140 arg1 % 1148:1148 2.22 [0.06]% 1137:1148 2.22 [0.06]% 1137:1148 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 7 52 theme de 1562:1563 arg1 synthesis 1570:1578 de novo synthesis 1562:1578 de novo synthesis of glutamine from glucose 1562:1604 Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase. 36031420 8 53 dep CONCLUSIONS 1734:1744 arg1 decreased 1776:1784 decreased 1776:1784 decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain 1776:1922 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 4 54 theme emission 708:715 arg1 tomography 737:746 Positron emission tomography-computed tomography 699:746 Positron emission tomography-computed tomography 699:746 Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms. 36031420 5 55 theme higher 1000:1005 arg1 concentrations 1007:1020 higher concentrations 1000:1020 higher concentrations of sevoflurane to present LORR 1000:1051 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 6 56 from brain 1310:1314 arg1 elevation 1233:1241 elevation 1233:1241 elevation 1233:1241 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 8 57 theme hypoxia 1759:1765 arg1 exposure 1767:1774 Intermittent hypoxia exposure 1746:1774 Intermittent hypoxia exposure 1746:1774 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 2 58 theme extensive 252:260 arg1 effects 281:287 extensive pathophysiological effects 252:287 extensive pathophysiological effects 252:287 Hypoxia exerts extensive pathophysiological effects on the brain; however, whether hypoxia influences sevoflurane sensitivity and its underlying mechanisms remain poorly understood. 36031420 2 59 theme pathophysiological 262:279 arg1 effects 281:287 extensive pathophysiological effects 252:287 extensive pathophysiological effects 252:287 Hypoxia exerts extensive pathophysiological effects on the brain; however, whether hypoxia influences sevoflurane sensitivity and its underlying mechanisms remain poorly understood. 36031420 1 60 theme BACKGROUND 132:141 arg1 Hypersensitivity 143:158 BACKGROUND Hypersensitivity 132:158 BACKGROUND Hypersensitivity to general anaesthetics 132:182 BACKGROUND Hypersensitivity to general anaesthetics predicts adverse postoperative outcomes in patients. 36031420 7 61 theme glutamate-glutamine 1637:1655 arg1 cycle 1657:1661 the glutamate-glutamine cycle 1633:1661 the glutamate-glutamine cycle 1633:1661 Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase. 36031420 6 62 theme modification 1294:1305 arg1 elevation 1233:1241 elevation 1233:1241 elevation 1233:1241 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 4 63 theme site-specific 806:818 arg1 mutagenesis 820:830 site-specific mutagenesis 806:830 site-specific mutagenesis 806:830 Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms. 36031420 8 64 theme O-GlcNAc-dependent 1848:1865 arg1 modulation 1867:1876 enhanced O-GlcNAc-dependent modulation 1839:1876 enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain 1839:1922 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 8 65 from brain 1918:1922 arg1 modulation 1867:1876 enhanced O-GlcNAc-dependent modulation 1839:1876 enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain 1839:1922 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 4 66 theme seahorse 768:775 arg1 analysis 777:784 seahorse analysis 768:784 seahorse analysis 768:784 Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms. 36031420 5 67 theme present 1040:1046 arg1 LORR 1048:1051 present LORR 1040:1051 present LORR 1040:1051 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 3 68 theme withdrawal 655:664 arg1 response 666:673 tail-pinch withdrawal response 644:673 tail-pinch withdrawal response (LTWR) 644:680 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 3 68 theme withdrawal 655:664 arg1 LTWR 676:679 LTWR 676:679 LTWR 676:679 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 4 69 theme tomography-computed 717:735 arg1 tomography 737:746 Positron emission tomography-computed tomography 699:746 Positron emission tomography-computed tomography 699:746 Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms. 36031420 6 70 theme selective 1489:1497 arg1 thiamet-G 1476:1484 thiamet-G 1476:1484 thiamet-G 1476:1484 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 6 70 theme selective 1489:1497 arg1 inhibitor 1511:1519 a selective O-GlcNAcase inhibitor 1487:1519 a selective O-GlcNAcase inhibitor 1487:1519 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 7 71 dep de 1562:1563 arg1 novo 1565:1568 novo 1565:1568 novo 1565:1568 Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase. 36031420 3 72 theme response 666:673 arg1 loss 601:604 loss 601:604 loss of righting reflex (LORR) 601:630 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 3 72 theme response 666:673 arg1 loss 636:639 loss 636:639 loss of tail-pinch withdrawal response (LTWR) 636:680 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 3 73 theme reflex 618:623 arg1 loss 601:604 loss 601:604 loss of righting reflex (LORR) 601:630 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 3 73 theme reflex 618:623 arg1 loss 636:639 loss 636:639 loss of tail-pinch withdrawal response (LTWR) 636:680 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 1 74 theme general 163:169 arg1 anaesthetics 171:182 general anaesthetics 163:182 general anaesthetics 163:182 BACKGROUND Hypersensitivity to general anaesthetics predicts adverse postoperative outcomes in patients. 36031420 6 75 theme O-GlcNAcase 1499:1509 arg1 thiamet-G 1476:1484 thiamet-G 1476:1484 thiamet-G 1476:1484 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 6 75 theme O-GlcNAcase 1499:1509 arg1 inhibitor 1511:1519 a selective O-GlcNAcase inhibitor 1487:1519 a selective O-GlcNAcase inhibitor 1487:1519 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 3 76 theme oxygen 460:465 arg1 % 469:469 oxygen 10% 460:469 oxygen 10% for 8 h day-1 460:483 METHODS Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. 36031420 8 77 theme cycle 1905:1909 arg1 modulation 1867:1876 enhanced O-GlcNAc-dependent modulation 1839:1876 enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain 1839:1922 CONCLUSIONS Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain. 36031420 5 78 dep concentrations 1007:1020 arg1 [0.14 1126:1130 [0.14 1126:1130 [0.14 1126:1130 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 5 78 dep concentrations 1007:1020 arg1 % 1084:1084 % 1084:1084 % 1084:1084 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 5 78 dep concentrations 1007:1020 arg1 P<0.01 1103:1108 P<0.01 1103:1108 P<0.01 1103:1108 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 5 78 dep concentrations 1007:1020 arg1 EC50LTWR 1111:1118 EC50LTWR 1111:1118 EC50LTWR 1111:1118 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 5 78 dep concentrations 1007:1020 arg1 1.61 1073:1076 1.61 1073:1076 1.61 1073:1076 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 5 78 dep concentrations 1007:1020 arg1 [0.04 1094:1098 [0.04 1094:1098 [0.04 1094:1098 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 5 78 dep concentrations 1007:1020 arg1 [0.03 1078:1082 [0.03 1078:1082 [0.03 1078:1082 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 5 78 dep concentrations 1007:1020 arg1 2.46 1121:1124 2.46 1121:1124 2.46 1121:1124 RESULTS Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). 36031420 6 79 theme N-acetylglucosamine 1263:1281 arg1 modification 1294:1305 protein O-linked N-acetylglucosamine (O-GlcNAc) modification 1246:1305 protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain 1246:1314 Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. 36031420 2 80 dep exerts 245:250 arg1 influences 328:337 influences 328:337 influences sevoflurane sensitivity 328:361 Hypoxia exerts extensive pathophysiological effects on the brain; however, whether hypoxia influences sevoflurane sensitivity and its underlying mechanisms remain poorly understood. 36031420 2 80 dep exerts 245:250 arg1 remain 393:398 remain 393:398 remain poorly understood 393:416 Hypoxia exerts extensive pathophysiological effects on the brain; however, whether hypoxia influences sevoflurane sensitivity and its underlying mechanisms remain poorly understood. 35316768 0 0 theme pancreatic 99:108 arg1 β-cells 110:116 pancreatic β-cells 99:116 pancreatic β-cells 99:116 O-GlcNAcylation of myocyte-specific enhancer factor 2D negatively regulates insulin secretion from pancreatic β-cells. 35316768 6 1 theme factor 1121:1126 arg1 knockdown 1091:1099 knockdown 1091:1099 knockdown of myocyte enhancer factor 2D (Mef2d) 1091:1137 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 5 2 theme Immunoprecipitation 852:870 arg1 analysis 882:889 Immunoprecipitation proteomic analysis 852:889 Immunoprecipitation proteomic analysis 852:889 Immunoprecipitation proteomic analysis identified six candidate proteins that were O-GlcNAcylated by high-glucose treatment, whereas the O-GlcNAcylations were removed by treatment with an incretin mimetic, exendin-4. 35316768 5 3 theme proteomic 872:880 arg1 analysis 882:889 Immunoprecipitation proteomic analysis 852:889 Immunoprecipitation proteomic analysis 852:889 Immunoprecipitation proteomic analysis identified six candidate proteins that were O-GlcNAcylated by high-glucose treatment, whereas the O-GlcNAcylations were removed by treatment with an incretin mimetic, exendin-4. 35316768 5 4 with treatment 1022:1030 arg1 exendin-4 1058:1066 an incretin mimetic, exendin-4 1037:1066 exendin-4 1058:1066 Immunoprecipitation proteomic analysis identified six candidate proteins that were O-GlcNAcylated by high-glucose treatment, whereas the O-GlcNAcylations were removed by treatment with an incretin mimetic, exendin-4. 35316768 2 5 theme molecular 371:379 arg1 mechanisms 381:390 the molecular mechanisms 367:390 the molecular mechanisms 367:390 These phenotypes are associated with altered glucose metabolism in pancreatic β-cells, although the molecular mechanisms remain unclear. 35316768 6 6 theme enhancer 1112:1119 arg1 factor 1121:1126 myocyte enhancer factor 2D 1104:1129 myocyte enhancer factor 2D (Mef2d) 1104:1137 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 6 6 theme enhancer 1112:1119 arg1 Mef2d 1132:1136 Mef2d 1132:1136 Mef2d 1132:1136 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 7 7 theme MIN6-K8 1308:1314 arg1 cells 1316:1320 MIN6-K8 cells 1308:1320 MIN6-K8 cells 1308:1320 Furthermore, knockout of Mef2d promoted GIIS in MIN6-K8 cells, whereas adenovirus-mediated rescue of Mef2d decreased GIIS in the knockout cells. 35316768 2 8 theme altered 308:314 arg1 metabolism 324:333 altered glucose metabolism 308:333 altered glucose metabolism in pancreatic β-cells 308:355 These phenotypes are associated with altered glucose metabolism in pancreatic β-cells, although the molecular mechanisms remain unclear. 35316768 6 9 theme myocyte 1104:1110 arg1 factor 1121:1126 myocyte enhancer factor 2D 1104:1129 myocyte enhancer factor 2D (Mef2d) 1104:1137 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 6 9 theme myocyte 1104:1110 arg1 Mef2d 1132:1136 Mef2d 1132:1136 Mef2d 1132:1136 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 3 10 gly glycosylation 519:531 arg1 insulin 613:619 insulin secretion 613:629 insulin secretion 613:629 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 8 11 theme insulin 1459:1465 arg1 secretion 1467:1475 insulin secretion 1459:1475 insulin secretion 1459:1475 These results suggest that Mef2d negatively regulates insulin secretion through O-GlcNAcylation. 35316768 7 12 theme Mef2d 1361:1365 arg1 rescue 1351:1356 adenovirus-mediated rescue 1331:1356 adenovirus-mediated rescue of Mef2d 1331:1365 Furthermore, knockout of Mef2d promoted GIIS in MIN6-K8 cells, whereas adenovirus-mediated rescue of Mef2d decreased GIIS in the knockout cells. 35316768 3 13 theme posttranslational 578:594 arg1 glycosylation 519:531 O-linked N-acetylglucosamine glycosylation 490:531 O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) 490:549 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 13 theme posttranslational 578:594 arg1 modification 596:607 a glucose-induced protein posttranslational modification 552:607 a glucose-induced protein posttranslational modification 552:607 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 5 14 theme mimetic 1049:1055 arg1 exendin-4 1058:1066 an incretin mimetic, exendin-4 1037:1066 exendin-4 1058:1066 Immunoprecipitation proteomic analysis identified six candidate proteins that were O-GlcNAcylated by high-glucose treatment, whereas the O-GlcNAcylations were removed by treatment with an incretin mimetic, exendin-4. 35316768 3 15 theme N-acetylglucosamine 499:517 arg1 O-GlcNAcylation 534:548 O-GlcNAcylation 534:548 O-GlcNAcylation 534:548 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 15 theme N-acetylglucosamine 499:517 arg1 glycosylation 519:531 O-linked N-acetylglucosamine glycosylation 490:531 O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) 490:549 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 15 theme N-acetylglucosamine 499:517 arg1 modification 596:607 a glucose-induced protein posttranslational modification 552:607 a glucose-induced protein posttranslational modification 552:607 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 1 16 from impairments 163:173 arg1 secretion 207:215 glucose-induced insulin secretion 183:215 glucose-induced insulin secretion (GIIS) 183:222 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 1 16 from impairments 163:173 arg1 IIIS 264:267 IIIS 264:267 IIIS 264:267 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 1 16 from impairments 163:173 arg1 secretion 253:261 incretin-induced insulin secretion 228:261 incretin-induced insulin secretion (IIIS) 228:268 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 1 16 from impairments 163:173 arg1 GIIS 218:221 GIIS 218:221 GIIS 218:221 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 1 17 theme glucose-induced 183:197 arg1 secretion 207:215 glucose-induced insulin secretion 183:215 glucose-induced insulin secretion (GIIS) 183:222 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 1 17 theme glucose-induced 183:197 arg1 GIIS 218:221 GIIS 218:221 GIIS 218:221 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 5 18 theme candidate 906:914 arg1 proteins 916:923 six candidate proteins 902:923 six candidate proteins that were O-GlcNAcylated by high-glucose treatment, whereas the O-GlcNAcylations were removed by treatment with an incretin mimetic, exendin-4 902:1066 Immunoprecipitation proteomic analysis identified six candidate proteins that were O-GlcNAcylated by high-glucose treatment, whereas the O-GlcNAcylations were removed by treatment with an incretin mimetic, exendin-4. 35316768 3 19 theme pancreatic 430:439 arg1 lines 448:452 MIN6-K8 pancreatic β-cell lines 422:452 MIN6-K8 pancreatic β-cell lines 422:452 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 19 theme pancreatic 430:439 arg1 model 459:463 a model 457:463 a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion 457:629 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 20 theme glucose-induced 554:568 arg1 glycosylation 519:531 O-linked N-acetylglucosamine glycosylation 490:531 O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) 490:549 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 20 theme glucose-induced 554:568 arg1 modification 596:607 a glucose-induced protein posttranslational modification 552:607 a glucose-induced protein posttranslational modification 552:607 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 1 21 theme insulin 199:205 arg1 secretion 207:215 glucose-induced insulin secretion 183:215 glucose-induced insulin secretion (GIIS) 183:222 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 1 21 theme insulin 199:205 arg1 GIIS 218:221 GIIS 218:221 GIIS 218:221 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 1 22 with Patients 119:126 arg1 diabetes 140:147 type 2 diabetes 133:147 type 2 diabetes 133:147 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 2 23 theme pancreatic 338:347 arg1 β-cells 349:355 pancreatic β-cells 338:355 pancreatic β-cells 338:355 These phenotypes are associated with altered glucose metabolism in pancreatic β-cells, although the molecular mechanisms remain unclear. 35316768 3 24 link O-linked 490:497 arg1 N-acetylglucosamine 499:517 O-linked N-acetylglucosamine 490:517 O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) 490:549 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 6 25 theme high-glucose 1171:1182 arg1 treatment 1184:1192 high-glucose treatment 1171:1192 high-glucose treatment 1171:1192 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 7 26 theme Mef2d 1285:1289 arg1 knockout 1273:1280 knockout 1273:1280 knockout 1273:1280 Furthermore, knockout of Mef2d promoted GIIS in MIN6-K8 cells, whereas adenovirus-mediated rescue of Mef2d decreased GIIS in the knockout cells. 35316768 4 27 gly O-GlcNAcylation 632:646 arg1 cells 693:697 high-glucose-treated MIN6-K8 cells 664:697 high-glucose-treated MIN6-K8 cells 664:697 O-GlcNAcylation was enhanced in high-glucose-treated MIN6-K8 cells, and high levels of O-GlcNAcylation attenuated PKA-dependent phosphorylation, suggesting that the two protein modifications may compete with each other. 35316768 3 28 theme insulin 613:619 arg1 secretion 621:629 insulin secretion 613:629 insulin secretion 613:629 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 4 29 theme O-GlcNAcylation 719:733 arg1 levels 709:714 high levels 704:714 high levels of O-GlcNAcylation 704:733 O-GlcNAcylation was enhanced in high-glucose-treated MIN6-K8 cells, and high levels of O-GlcNAcylation attenuated PKA-dependent phosphorylation, suggesting that the two protein modifications may compete with each other. 35316768 0 30 theme enhancer 36:43 arg1 2D 52:53 myocyte-specific enhancer factor 2D 19:53 myocyte-specific enhancer factor 2D 19:53 O-GlcNAcylation of myocyte-specific enhancer factor 2D negatively regulates insulin secretion from pancreatic β-cells. 35316768 6 31 theme insulin 1148:1154 arg1 secretion 1156:1164 insulin secretion 1148:1164 insulin secretion 1148:1164 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 0 32 theme myocyte-specific 19:34 arg1 2D 52:53 myocyte-specific enhancer factor 2D 19:53 myocyte-specific enhancer factor 2D 19:53 O-GlcNAcylation of myocyte-specific enhancer factor 2D negatively regulates insulin secretion from pancreatic β-cells. 35316768 7 33 from GIIS 1300:1303 arg1 cells 1316:1320 MIN6-K8 cells 1308:1320 MIN6-K8 cells 1308:1320 Furthermore, knockout of Mef2d promoted GIIS in MIN6-K8 cells, whereas adenovirus-mediated rescue of Mef2d decreased GIIS in the knockout cells. 35316768 2 34 theme glucose 316:322 arg1 metabolism 324:333 altered glucose metabolism 308:333 altered glucose metabolism in pancreatic β-cells 308:355 These phenotypes are associated with altered glucose metabolism in pancreatic β-cells, although the molecular mechanisms remain unclear. 35316768 0 35 theme 2D 52:53 arg1 O-GlcNAcylation 0:14 O-GlcNAcylation 0:14 O-GlcNAcylation of myocyte-specific enhancer factor 2D 0:53 O-GlcNAcylation of myocyte-specific enhancer factor 2D negatively regulates insulin secretion from pancreatic β-cells. 35316768 5 36 theme high-glucose 953:964 arg1 treatment 966:974 high-glucose treatment 953:974 high-glucose treatment 953:974 Immunoprecipitation proteomic analysis identified six candidate proteins that were O-GlcNAcylated by high-glucose treatment, whereas the O-GlcNAcylations were removed by treatment with an incretin mimetic, exendin-4. 35316768 4 37 theme high 704:707 arg1 levels 709:714 high levels 704:714 high levels of O-GlcNAcylation 704:733 O-GlcNAcylation was enhanced in high-glucose-treated MIN6-K8 cells, and high levels of O-GlcNAcylation attenuated PKA-dependent phosphorylation, suggesting that the two protein modifications may compete with each other. 35316768 0 38 theme factor 45:50 arg1 2D 52:53 myocyte-specific enhancer factor 2D 19:53 myocyte-specific enhancer factor 2D 19:53 O-GlcNAcylation of myocyte-specific enhancer factor 2D negatively regulates insulin secretion from pancreatic β-cells. 35316768 3 39 theme β-cell 441:446 arg1 lines 448:452 MIN6-K8 pancreatic β-cell lines 422:452 MIN6-K8 pancreatic β-cell lines 422:452 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 39 theme β-cell 441:446 arg1 model 459:463 a model 457:463 a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion 457:629 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 1 40 theme incretin-induced 228:243 arg1 IIIS 264:267 IIIS 264:267 IIIS 264:267 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 1 40 theme incretin-induced 228:243 arg1 secretion 253:261 incretin-induced insulin secretion 228:261 incretin-induced insulin secretion (IIIS) 228:268 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 1 41 theme type 133:136 arg1 diabetes 140:147 type 2 diabetes 133:147 type 2 diabetes 133:147 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 3 42 theme MIN6-K8 422:428 arg1 lines 448:452 MIN6-K8 pancreatic β-cell lines 422:452 MIN6-K8 pancreatic β-cell lines 422:452 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 42 theme MIN6-K8 422:428 arg1 model 459:463 a model 457:463 a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion 457:629 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 43 used used 417:420 arg2 we 414:415 we 414:415 we 414:415 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 7 44 theme knockout 1389:1396 arg1 cells 1398:1402 the knockout cells 1385:1402 the knockout cells 1385:1402 Furthermore, knockout of Mef2d promoted GIIS in MIN6-K8 cells, whereas adenovirus-mediated rescue of Mef2d decreased GIIS in the knockout cells. 35316768 3 45 theme glycosylation 519:531 arg1 effect 480:485 the effect 476:485 the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion 476:629 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 46 from effect 480:485 arg1 secretion 621:629 insulin secretion 613:629 insulin secretion 613:629 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 4 47 theme protein 801:807 arg1 modifications 809:821 the two protein modifications 793:821 the two protein modifications 793:821 O-GlcNAcylation was enhanced in high-glucose-treated MIN6-K8 cells, and high levels of O-GlcNAcylation attenuated PKA-dependent phosphorylation, suggesting that the two protein modifications may compete with each other. 35316768 1 48 theme insulin 245:251 arg1 IIIS 264:267 IIIS 264:267 IIIS 264:267 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 1 48 theme insulin 245:251 arg1 secretion 253:261 incretin-induced insulin secretion 228:261 incretin-induced insulin secretion (IIIS) 228:268 Patients with type 2 diabetes often exhibit impairments in both glucose-induced insulin secretion (GIIS) and incretin-induced insulin secretion (IIIS). 35316768 3 49 theme protein 570:576 arg1 glycosylation 519:531 O-linked N-acetylglucosamine glycosylation 490:531 O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) 490:549 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 3 49 theme protein 570:576 arg1 modification 596:607 a glucose-induced protein posttranslational modification 552:607 a glucose-induced protein posttranslational modification 552:607 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 6 50 from level 1208:1212 arg1 cells 1253:1257 MIN6-K8 cells 1245:1257 MIN6-K8 cells 1245:1257 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 3 51 theme O-linked 490:497 arg1 N-acetylglucosamine 499:517 O-linked N-acetylglucosamine 490:517 O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) 490:549 Here, we used MIN6-K8 pancreatic β-cell lines as a model to examine the effect of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation), a glucose-induced protein posttranslational modification, on insulin secretion. 35316768 6 52 theme MIN6-K8 1245:1251 arg1 cells 1253:1257 MIN6-K8 cells 1245:1257 MIN6-K8 cells 1245:1257 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 6 53 theme Mef2d 1236:1240 arg1 O-GlcNAcylation 1217:1231 O-GlcNAcylation 1217:1231 O-GlcNAcylation of Mef2d 1217:1240 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 7 54 theme adenovirus-mediated 1331:1349 arg1 rescue 1351:1356 adenovirus-mediated rescue 1331:1356 adenovirus-mediated rescue of Mef2d 1331:1365 Furthermore, knockout of Mef2d promoted GIIS in MIN6-K8 cells, whereas adenovirus-mediated rescue of Mef2d decreased GIIS in the knockout cells. 35316768 0 55 from β-cells 110:116 arg1 secretion 84:92 insulin secretion 76:92 insulin secretion from pancreatic β-cells 76:116 O-GlcNAcylation of myocyte-specific enhancer factor 2D negatively regulates insulin secretion from pancreatic β-cells. 35316768 6 56 theme O-GlcNAcylation 1217:1231 arg1 level 1208:1212 the level 1204:1212 the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells 1204:1257 Among these proteins, knockdown of myocyte enhancer factor 2D (Mef2d) enhanced insulin secretion, and high-glucose treatment increased the level of O-GlcNAcylation of Mef2d in MIN6-K8 cells. 35316768 4 57 theme MIN6-K8 685:691 arg1 cells 693:697 high-glucose-treated MIN6-K8 cells 664:697 high-glucose-treated MIN6-K8 cells 664:697 O-GlcNAcylation was enhanced in high-glucose-treated MIN6-K8 cells, and high levels of O-GlcNAcylation attenuated PKA-dependent phosphorylation, suggesting that the two protein modifications may compete with each other. 35316768 0 58 theme insulin 76:82 arg1 secretion 84:92 insulin secretion 76:92 insulin secretion from pancreatic β-cells 76:116 O-GlcNAcylation of myocyte-specific enhancer factor 2D negatively regulates insulin secretion from pancreatic β-cells. 35316768 4 59 theme PKA-dependent 746:758 arg1 phosphorylation 760:774 PKA-dependent phosphorylation 746:774 PKA-dependent phosphorylation 746:774 O-GlcNAcylation was enhanced in high-glucose-treated MIN6-K8 cells, and high levels of O-GlcNAcylation attenuated PKA-dependent phosphorylation, suggesting that the two protein modifications may compete with each other. 35316768 2 60 from metabolism 324:333 arg1 β-cells 349:355 pancreatic β-cells 338:355 pancreatic β-cells 338:355 These phenotypes are associated with altered glucose metabolism in pancreatic β-cells, although the molecular mechanisms remain unclear. 35316768 4 61 theme high-glucose-treated 664:683 arg1 cells 693:697 high-glucose-treated MIN6-K8 cells 664:697 high-glucose-treated MIN6-K8 cells 664:697 O-GlcNAcylation was enhanced in high-glucose-treated MIN6-K8 cells, and high levels of O-GlcNAcylation attenuated PKA-dependent phosphorylation, suggesting that the two protein modifications may compete with each other. 35796294 3 0 theme action 668:673 arg1 mechanism 655:663 an autonomous mechanism 641:663 an autonomous mechanism of action 641:673 Importantly, the catalytic competence of TMPRSS13 is essential for stem region cleavage, suggesting an autonomous mechanism of action. 35796294 2 1 theme extracellular 343:355 arg1 region 371:376 the extracellular TMPRSS13 stem region 339:376 the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 339:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 4 2 theme catalytic 818:826 arg1 activity 828:835 catalytic activity 818:835 catalytic activity 818:835 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 2 3 theme novel 243:247 arg1 mechanism 268:276 a novel post-translational mechanism 241:276 a novel post-translational mechanism important for TMPRSS13 function 241:308 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 1 4 theme II 172:173 arg1 family 212:217 the type II transmembrane serine protease (TTSP) family 163:217 the type II transmembrane serine protease (TTSP) family 163:217 TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. 35796294 7 5 theme TMPRSS13 1367:1374 arg1 localization 1351:1362 localization 1351:1362 localization 1351:1362 These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. 35796294 7 5 theme TMPRSS13 1367:1374 arg1 function 1338:1345 function 1338:1345 function 1338:1345 These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. 35796294 0 6 theme non-catalytic 112:124 arg1 region 131:136 the non-catalytic stem region 108:136 the non-catalytic stem region 108:136 TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region. 35796294 5 7 theme A 1053:1053 arg1 domain 1055:1060 the low-density lipoprotein receptor class A domain 1010:1060 the low-density lipoprotein receptor class A domain 1010:1060 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 1 8 theme serine 189:194 arg1 family 212:217 the type II transmembrane serine protease (TTSP) family 163:217 the type II transmembrane serine protease (TTSP) family 163:217 TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. 35796294 2 9 theme SRCR 527:530 arg1 domain 533:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 8 10 theme interconnected 1432:1445 arg1 mechanisms 1458:1467 complex interconnected regulatory mechanisms 1424:1467 complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions 1424:1602 Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions. 35796294 6 11 theme TMPRSS13 1211:1218 arg1 steps 1202:1206 the aforementioned functional processing steps 1161:1206 the aforementioned functional processing steps of TMPRSS13 1161:1218 Mutation of R223 causes a reduction in the aforementioned functional processing steps of TMPRSS13. 35796294 3 12 theme TMPRSS13 582:589 arg1 essential 594:602 essential 594:602 essential 594:602 Importantly, the catalytic competence of TMPRSS13 is essential for stem region cleavage, suggesting an autonomous mechanism of action. 35796294 3 12 theme TMPRSS13 582:589 arg1 competence 568:577 the catalytic competence 554:577 the catalytic competence of TMPRSS13 554:589 Importantly, the catalytic competence of TMPRSS13 is essential for stem region cleavage, suggesting an autonomous mechanism of action. 35796294 8 13 theme mechanisms 1458:1467 arg1 presence 1412:1419 the presence 1408:1419 the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions 1408:1602 Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions. 35796294 5 14 theme low-density 1014:1024 arg1 lipoprotein 1026:1036 the low-density lipoprotein 1010:1036 the low-density lipoprotein receptor class A domain 1010:1060 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 4 15 theme cell 878:881 arg1 expression 891:900 cell surface expression 878:900 cell surface expression 878:900 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 6 16 theme functional 1180:1189 arg1 steps 1202:1206 the aforementioned functional processing steps 1161:1206 the aforementioned functional processing steps of TMPRSS13 1161:1218 Mutation of R223 causes a reduction in the aforementioned functional processing steps of TMPRSS13. 35796294 4 17 theme basic 712:716 arg1 acids 724:728 the 10 basic amino acids 705:728 the 10 basic amino acids (four arginine and six lysine residues) 705:768 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 5 18 theme receptor 1038:1045 arg1 domain 1055:1060 the low-density lipoprotein receptor class A domain 1010:1060 the low-density lipoprotein receptor class A domain 1010:1060 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 3 19 theme stem 608:611 arg1 cleavage 620:627 stem region cleavage 608:627 stem region cleavage 608:627 Importantly, the catalytic competence of TMPRSS13 is essential for stem region cleavage, suggesting an autonomous mechanism of action. 35796294 5 20 theme stem 1100:1103 arg1 cleavage 1112:1119 stem region cleavage 1100:1119 stem region cleavage 1100:1119 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 2 21 theme rich 521:524 arg1 domain 533:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 7 22 theme localization 1351:1362 arg1 regulators 1320:1329 regulators 1320:1329 regulators of the function and localization of TMPRSS13 1320:1374 These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. 35796294 0 23 theme proteolytic 80:90 arg1 cleavage 92:99 proteolytic cleavage 80:99 proteolytic cleavage within the non-catalytic stem region 80:136 TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region. 35796294 5 24 theme SRCR 1070:1073 arg1 domain 1075:1080 the SRCR domain 1066:1080 the SRCR domain 1066:1080 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 5 25 theme individual 938:947 arg1 residues 958:965 individual arginine residues 938:965 individual arginine residues 938:965 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 2 26 theme receptor 503:510 arg1 domain 533:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 8 27 theme cell-surface 1515:1526 arg1 levels 1505:1510 the proper levels 1494:1510 the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis 1494:1573 Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions. 35796294 2 28 link N-linked 441:448 arg1 glycosylation 450:462 N-linked glycosylation 441:462 N-linked glycosylation 441:462 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 4 29 theme lysine 753:758 arg1 residues 760:767 four arginine and six lysine residues 731:767 residues 760:767 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 2 30 theme transmembrane 398:410 arg1 glycosylation 450:462 N-linked glycosylation 441:462 N-linked glycosylation 441:462 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 30 theme transmembrane 398:410 arg1 domain 412:417 the transmembrane domain 394:417 the transmembrane domain 394:417 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 5 31 theme residues 958:965 arg1 analysis 926:933 Mutation analysis 917:933 Mutation analysis of individual arginine residues 917:965 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 2 32 theme glycosylation 450:462 arg1 site 433:436 the first site 423:436 the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 423:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 32 theme glycosylation 450:462 arg1 glycosylation 450:462 N-linked glycosylation 441:462 N-linked glycosylation 441:462 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 32 theme glycosylation 450:462 arg1 domain 412:417 the transmembrane domain 394:417 the transmembrane domain 394:417 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 8 33 theme pericellular 1532:1543 arg1 proteolysis 1563:1573 pericellular TMPRSS13-mediated proteolysis 1532:1573 pericellular TMPRSS13-mediated proteolysis 1532:1573 Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions. 35796294 4 34 theme acids 724:728 arg1 mutagenesis 690:700 Site-directed mutagenesis 676:700 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region 676:783 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 0 35 theme TMPRSS13 0:7 arg1 activation 17:26 TMPRSS13 zymogen activation 0:26 TMPRSS13 zymogen activation 0:26 TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region. 35796294 8 36 theme proteolysis 1563:1573 arg1 levels 1505:1510 the proper levels 1494:1510 the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis 1494:1573 Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions. 35796294 2 37 theme first 427:431 arg1 site 433:436 the first site 423:436 the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 423:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 37 theme first 427:431 arg1 glycosylation 450:462 N-linked glycosylation 441:462 N-linked glycosylation 441:462 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 7 38 theme post-translational 1284:1301 arg1 modifications 1303:1315 different post-translational modifications 1274:1315 different post-translational modifications 1274:1315 These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. 35796294 8 39 theme homeostatic 1581:1591 arg1 conditions 1593:1602 homeostatic conditions 1581:1602 homeostatic conditions 1581:1602 Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions. 35796294 0 40 theme surface 29:35 arg1 localization 37:48 surface localization 29:48 surface localization 29:48 TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region. 35796294 5 41 theme located 994:1000 arg1 R223 978:981 R223 978:981 R223 978:981 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 5 41 theme located 994:1000 arg1 residue 986:992 a residue 984:992 a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain 984:1080 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 2 42 theme asparagine 467:476 arg1 N 479:479 asparagine (N)-250 467:484 asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 467:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 1 43 theme TTSP 206:209 arg1 family 212:217 the type II transmembrane serine protease (TTSP) family 163:217 the type II transmembrane serine protease (TTSP) family 163:217 TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. 35796294 2 44 gly glycosylation 450:462 arg2 site 433:436 the first site 423:436 the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 423:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 44 gly glycosylation 450:462 arg2 glycosylation 450:462 N-linked glycosylation 441:462 N-linked glycosylation 441:462 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 3 45 theme autonomous 644:653 arg1 mechanism 655:663 an autonomous mechanism 641:663 an autonomous mechanism of action 641:673 Importantly, the catalytic competence of TMPRSS13 is essential for stem region cleavage, suggesting an autonomous mechanism of action. 35796294 8 46 theme complex 1424:1430 arg1 mechanisms 1458:1467 complex interconnected regulatory mechanisms 1424:1467 complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions 1424:1602 Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions. 35796294 1 47 theme family 212:217 arg1 TMPRSS13 139:146 TMPRSS13 139:146 TMPRSS13 139:146 TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. 35796294 1 47 theme family 212:217 arg1 member 153:158 a member 151:158 a member of the type II transmembrane serine protease (TTSP) family 151:217 TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. 35796294 2 48 theme TMPRSS13 357:364 arg1 region 371:376 the extracellular TMPRSS13 stem region 339:376 the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 339:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 4 49 theme TMPRSS13 840:847 arg1 activity 828:835 catalytic activity 818:835 catalytic activity 818:835 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 4 49 theme TMPRSS13 840:847 arg1 expression 891:900 cell surface expression 878:900 cell surface expression 878:900 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 4 49 theme TMPRSS13 840:847 arg1 shedding 907:914 shedding 907:914 shedding 907:914 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 4 49 theme TMPRSS13 840:847 arg1 phosphorylation 861:875 phosphorylation 861:875 phosphorylation 861:875 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 4 49 theme TMPRSS13 840:847 arg1 activation 803:812 zymogen activation 795:812 zymogen activation 795:812 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 2 50 theme important 278:286 arg1 mechanism 268:276 a novel post-translational mechanism 241:276 a novel post-translational mechanism important for TMPRSS13 function 241:308 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 51 theme post-translational 249:266 arg1 mechanism 268:276 a novel post-translational mechanism 241:276 a novel post-translational mechanism important for TMPRSS13 function 241:308 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 6 52 theme R223 1134:1137 arg1 Mutation 1122:1129 Mutation 1122:1129 Mutation of R223 1122:1137 Mutation of R223 causes a reduction in the aforementioned functional processing steps of TMPRSS13. 35796294 1 53 theme type 167:170 arg1 family 212:217 the type II transmembrane serine protease (TTSP) family 163:217 the type II transmembrane serine protease (TTSP) family 163:217 TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. 35796294 2 54 dep characterize 228:239 arg1 cleavage 323:330 proteolytic cleavage 311:330 proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 311:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 0 55 theme stem 126:129 arg1 region 131:136 the non-catalytic stem region 108:136 the non-catalytic stem region 108:136 TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region. 35796294 2 56 theme TMPRSS13 292:299 arg1 function 301:308 TMPRSS13 function 292:308 TMPRSS13 function 292:308 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 1 57 theme transmembrane 175:187 arg1 family 212:217 the type II transmembrane serine protease (TTSP) family 163:217 the type II transmembrane serine protease (TTSP) family 163:217 TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. 35796294 4 58 theme surface 883:889 arg1 expression 891:900 cell surface expression 878:900 cell surface expression 878:900 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 8 59 theme regulatory 1447:1456 arg1 mechanisms 1458:1467 complex interconnected regulatory mechanisms 1424:1467 complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions 1424:1602 Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions. 35796294 1 60 theme protease 196:203 arg1 family 212:217 the type II transmembrane serine protease (TTSP) family 163:217 the type II transmembrane serine protease (TTSP) family 163:217 TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. 35796294 3 61 theme catalytic 558:566 arg1 essential 594:602 essential 594:602 essential 594:602 Importantly, the catalytic competence of TMPRSS13 is essential for stem region cleavage, suggesting an autonomous mechanism of action. 35796294 3 61 theme catalytic 558:566 arg1 competence 568:577 the catalytic competence 554:577 the catalytic competence of TMPRSS13 554:589 Importantly, the catalytic competence of TMPRSS13 is essential for stem region cleavage, suggesting an autonomous mechanism of action. 35796294 6 62 theme processing 1191:1200 arg1 steps 1202:1206 the aforementioned functional processing steps 1161:1206 the aforementioned functional processing steps of TMPRSS13 1161:1218 Mutation of R223 causes a reduction in the aforementioned functional processing steps of TMPRSS13. 35796294 5 63 theme lipoprotein 1026:1036 arg1 domain 1055:1060 the low-density lipoprotein receptor class A domain 1010:1060 the low-density lipoprotein receptor class A domain 1010:1060 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 4 64 dep acids 724:728 arg1 residues 760:767 four arginine and six lysine residues 731:767 residues 760:767 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 4 64 dep acids 724:728 arg1 arginine 736:743 four arginine and six lysine residues 731:767 arginine 736:743 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 6 65 theme aforementioned 1165:1178 arg1 steps 1202:1206 the aforementioned functional processing steps 1161:1206 the aforementioned functional processing steps of TMPRSS13 1161:1218 Mutation of R223 causes a reduction in the aforementioned functional processing steps of TMPRSS13. 35796294 5 66 theme class 1047:1051 arg1 domain 1055:1060 the low-density lipoprotein receptor class A domain 1010:1060 the low-density lipoprotein receptor class A domain 1010:1060 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 8 67 theme proper 1498:1503 arg1 levels 1505:1510 the proper levels 1494:1510 the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis 1494:1573 Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions. 35796294 7 68 theme function 1338:1345 arg1 regulators 1320:1329 regulators 1320:1329 regulators of the function and localization of TMPRSS13 1320:1374 These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. 35796294 4 69 theme Site-directed 676:688 arg1 mutagenesis 690:700 Site-directed mutagenesis 676:700 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region 676:783 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 5 70 theme region 1105:1110 arg1 cleavage 1112:1119 stem region cleavage 1100:1119 stem region cleavage 1100:1119 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 2 71 theme cysteine 512:519 arg1 domain 533:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 7 72 dep function 1338:1345 arg1 the 1334:1336 the 1334:1336 the 1334:1336 These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. 35796294 5 73 theme arginine 949:956 arg1 residues 958:965 individual arginine residues 938:965 individual arginine residues 938:965 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 2 74 theme scavenger 493:501 arg1 domain 533:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 75 from N 479:479 arg1 glycosylation 450:462 N-linked glycosylation 441:462 N-linked glycosylation 441:462 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 75 from N 479:479 arg1 site 433:436 the first site 423:436 the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 423:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 75 from N 479:479 arg1 domain 533:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 the scavenger receptor cysteine rich (SRCR) domain 489:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 75 from N 479:479 arg1 domain 412:417 the transmembrane domain 394:417 the transmembrane domain 394:417 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 6 76 from reduction 1148:1156 arg1 steps 1202:1206 the aforementioned functional processing steps 1161:1206 the aforementioned functional processing steps of TMPRSS13 1161:1218 Mutation of R223 causes a reduction in the aforementioned functional processing steps of TMPRSS13. 35796294 0 77 theme zymogen 9:15 arg1 activation 17:26 TMPRSS13 zymogen activation 0:26 TMPRSS13 zymogen activation 0:26 TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region. 35796294 7 78 theme modifications 1303:1315 arg1 roles 1265:1269 the roles 1261:1269 the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13 1261:1374 These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. 35796294 2 79 theme N-linked 441:448 arg1 glycosylation 450:462 N-linked glycosylation 441:462 N-linked glycosylation 441:462 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 4 80 theme amino 718:722 arg1 acids 724:728 the 10 basic amino acids 705:728 the 10 basic amino acids (four arginine and six lysine residues) 705:768 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 2 81 theme located 378:384 arg1 region 371:376 the extracellular TMPRSS13 stem region 339:376 the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 339:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 5 82 theme Mutation 917:924 arg1 analysis 926:933 Mutation analysis 917:933 Mutation analysis of individual arginine residues 917:965 Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. 35796294 7 83 theme different 1274:1282 arg1 modifications 1303:1315 different post-translational modifications 1274:1315 different post-translational modifications 1274:1315 These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. 35796294 3 84 theme region 613:618 arg1 cleavage 620:627 stem region cleavage 608:627 stem region cleavage 608:627 Importantly, the catalytic competence of TMPRSS13 is essential for stem region cleavage, suggesting an autonomous mechanism of action. 35796294 8 85 theme TMPRSS13-mediated 1545:1561 arg1 proteolysis 1563:1573 pericellular TMPRSS13-mediated proteolysis 1532:1573 pericellular TMPRSS13-mediated proteolysis 1532:1573 Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions. 35796294 4 86 theme zymogen 795:801 arg1 activation 803:812 zymogen activation 795:812 zymogen activation 795:812 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35796294 7 87 theme further 1240:1246 arg1 insight 1248:1254 further insight 1240:1254 further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13 1240:1374 These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. 35796294 2 88 theme proteolytic 311:321 arg1 cleavage 323:330 proteolytic cleavage 311:330 proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 311:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 2 89 theme stem 366:369 arg1 region 371:376 the extracellular TMPRSS13 stem region 339:376 the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain 339:538 Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. 35796294 4 90 from mutagenesis 690:700 arg1 region 778:783 this region 773:783 this region 773:783 Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. 35602895 8 0 theme AhXTH 906:910 arg1 genes 912:916 All AhXTH genes 902:916 All AhXTH genes 902:916 All AhXTH genes were unevenly distributed on the 18 peanut chromosomes, with the exception of chr. 35602895 14 1 theme higher 2150:2155 arg1 levels 2168:2173 higher expression levels 2150:2173 higher expression levels 2150:2173 The results of GUS histochemical staining showed that AhXTH4 was mainly expressed in germinated seeds and etiolated seedlings and had higher expression levels in elongated hypocotyls. 35602895 12 2 theme AhXTH 1703:1707 arg1 genes 1709:1713 26 AhXTH genes 1700:1713 26 AhXTH genes 1700:1713 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 13 3 theme real-time 1928:1936 arg1 PCR 1938:1940 quantitative real-time PCR 1915:1940 quantitative real-time PCR 1915:1940 The results of quantitative real-time PCR also confirmed that some AhXTHs were upregulated during seed germination. 35602895 11 4 theme Conserved 1343:1351 arg1 motif 1353:1357 Conserved motif 1343:1357 Conserved motif analysis 1343:1366 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 10 5 theme duplications 1304:1315 arg1 pairs 1249:1253 42 pairs 1246:1253 42 pairs of segmental duplications 1246:1279 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 10 5 theme duplications 1304:1315 arg1 pairs 1288:1292 23 pairs 1285:1292 23 pairs of tandem duplications 1285:1315 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 10 6 theme distribution 1121:1132 arg1 pattern 1134:1140 chromosomal distribution pattern 1109:1140 chromosomal distribution pattern 1109:1140 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 4 7 theme previous 410:417 arg1 study 419:423 Our previous study 406:423 Our previous study 406:423 Our previous study found that some peanut XTHs (xyloglucan endotransglucosylases/hydrolases) were expressed at higher levels at the newly germinated stage. 35602895 14 8 theme etiolated 2122:2130 arg1 seedlings 2132:2140 etiolated seedlings 2122:2140 etiolated seedlings 2122:2140 The results of GUS histochemical staining showed that AhXTH4 was mainly expressed in germinated seeds and etiolated seedlings and had higher expression levels in elongated hypocotyls. 35602895 15 9 theme crucial 2235:2241 arg1 role 2243:2246 a crucial role 2233:2246 a crucial role 2233:2246 AhXTH4 was also verified to play a crucial role in the cell elongation of hypocotyls during seed germination. 35602895 2 10 theme seedling 284:291 arg1 emergence 293:301 seedling emergence 284:301 seedling emergence 284:301 Improving the germination rate of seeds and the consistency of seedling emergence in the field could improve crop yields. 35602895 1 11 theme new 199:201 arg1 cycle 214:218 a new plant life cycle 197:218 a new plant life cycle 197:218 Seed germination marks the beginning of a new plant life cycle. 35602895 11 12 theme secondary 1504:1512 arg1 loops 1525:1529 the conserved secondary structural loops 1-3 1490:1533 the conserved secondary structural loops 1-3 in members of the same group 1490:1562 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 1 13 theme life 209:212 arg1 cycle 214:218 a new plant life cycle 197:218 a new plant life cycle 197:218 Seed germination marks the beginning of a new plant life cycle. 35602895 7 14 theme IIIA 877:880 arg1 subgroups 856:864 three subgroups 850:864 three subgroups 850:864 Phylogenetic analysis showed that these AhXTHs, along with 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean, were classified into three subgroups: the I/II, IIIA and IIIB subclades. 35602895 7 14 theme IIIA 877:880 arg1 subclades 891:899 IIIA and IIIB subclades 877:899 IIIA and IIIB subclades 877:899 Phylogenetic analysis showed that these AhXTHs, along with 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean, were classified into three subgroups: the I/II, IIIA and IIIB subclades. 35602895 8 15 theme peanut 954:959 arg1 chromosomes 961:971 the 18 peanut chromosomes 947:971 the 18 peanut chromosomes 947:971 All AhXTH genes were unevenly distributed on the 18 peanut chromosomes, with the exception of chr. 35602895 13 16 theme PCR 1938:1940 arg1 results 1904:1910 The results 1900:1910 The results of quantitative real-time PCR 1900:1940 The results of quantitative real-time PCR also confirmed that some AhXTHs were upregulated during seed germination. 35602895 11 17 gly glycosylation 1456:1468 arg2 sites 1470:1474 N-linked glycosylation sites 1447:1474 N-linked glycosylation sites 1447:1474 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 12 18 theme AhXTHs 1861:1866 arg1 roles 1852:1856 the important roles 1838:1856 the important roles of AhXTHs in regulating seed germination 1838:1897 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 4 19 theme xyloglucan 454:463 arg1 XTHs 448:451 some peanut XTHs 436:451 some peanut XTHs (xyloglucan endotransglucosylases/hydrolases) 436:497 Our previous study found that some peanut XTHs (xyloglucan endotransglucosylases/hydrolases) were expressed at higher levels at the newly germinated stage. 35602895 4 19 theme xyloglucan 454:463 arg1 endotransglucosylases/hydrolases 465:496 xyloglucan endotransglucosylases/hydrolases 454:496 xyloglucan endotransglucosylases/hydrolases 454:496 Our previous study found that some peanut XTHs (xyloglucan endotransglucosylases/hydrolases) were expressed at higher levels at the newly germinated stage. 35602895 2 20 theme germination 235:245 arg1 rate 247:250 the germination rate 231:250 the germination rate of seeds 231:259 Improving the germination rate of seeds and the consistency of seedling emergence in the field could improve crop yields. 35602895 5 21 from family 595:600 arg1 peanut 605:610 peanut 605:610 peanut 605:610 However, studies of the XTH gene family in peanut have not been reported. 35602895 12 22 theme seeds 1655:1659 arg1 analysis 1584:1591 Expression profile analysis 1565:1591 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data 1565:1684 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 9 23 dep four 1087:1090 arg1 to 1084:1085 to 1084:1085 to 1084:1085 07 and 17, and they had relatively conserved exon-intron patterns, most with three to four introns. 35602895 12 24 theme transcriptome 1667:1679 arg1 data 1681:1684 transcriptome data 1667:1684 transcriptome data 1667:1684 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 11 25 from loops 1525:1529 arg1 members 1538:1544 members 1538:1544 members of the same group 1538:1562 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 3 26 theme Many 343:346 arg1 genes 348:352 Many genes 343:352 Many genes 343:352 Many genes are involved in the regulation of seed germination. 35602895 11 27 theme conserved 1420:1428 arg1 domain 1436:1441 the conserved ExDxE domain 1416:1441 the conserved ExDxE domain 1416:1441 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 4 28 theme higher 517:522 arg1 levels 524:529 higher levels 517:529 higher levels 517:529 Our previous study found that some peanut XTHs (xyloglucan endotransglucosylases/hydrolases) were expressed at higher levels at the newly germinated stage. 35602895 0 29 from profiles 123:130 arg1 peanut 95:100 peanut 95:100 peanut 95:100 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 5 30 from peanut 605:610 arg1 studies 571:577 studies 571:577 studies of the XTH gene family in peanut 571:610 However, studies of the XTH gene family in peanut have not been reported. 35602895 14 31 theme staining 2049:2056 arg1 results 2020:2026 The results 2016:2026 The results of GUS histochemical staining 2016:2056 The results of GUS histochemical staining showed that AhXTH4 was mainly expressed in germinated seeds and etiolated seedlings and had higher expression levels in elongated hypocotyls. 35602895 11 32 theme N-linked 1447:1454 arg1 sites 1470:1474 N-linked glycosylation sites 1447:1474 N-linked glycosylation sites 1447:1474 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 0 33 theme expression 112:121 arg1 profiles 123:130 their expression profiles 106:130 their expression profiles during seed germination 106:154 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 12 34 theme important 1842:1850 arg1 roles 1852:1856 the important roles 1838:1856 the important roles of AhXTHs in regulating seed germination 1838:1897 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 12 35 theme seeds 1614:1618 arg1 analysis 1584:1591 Expression profile analysis 1565:1591 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data 1565:1684 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 14 36 theme GUS 2031:2033 arg1 staining 2049:2056 GUS histochemical staining 2031:2056 GUS histochemical staining 2031:2056 The results of GUS histochemical staining showed that AhXTH4 was mainly expressed in germinated seeds and etiolated seedlings and had higher expression levels in elongated hypocotyls. 35602895 10 37 theme many 1211:1214 arg1 pairs 1249:1253 42 pairs 1246:1253 42 pairs of segmental duplications 1246:1279 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 10 37 theme many 1211:1214 arg1 pairs 1288:1292 23 pairs 1285:1292 23 pairs of tandem duplications 1285:1315 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 10 37 theme many 1211:1214 arg1 events 1228:1233 many replication events 1211:1233 many replication events 1211:1233 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 9 38 contain had 1021:1023 arg2 patterns 1058:1065 relatively conserved exon-intron patterns 1025:1065 relatively conserved exon-intron patterns 1025:1065 07 and 17, and they had relatively conserved exon-intron patterns, most with three to four introns. 35602895 9 38 contain had 1021:1023 arg1 they 1016:1019 they 1016:1019 they 1016:1019 07 and 17, and they had relatively conserved exon-intron patterns, most with three to four introns. 35602895 12 39 theme seed 1805:1808 arg1 germination 1810:1820 the seed germination 1801:1820 the seed germination stage 1801:1826 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 7 40 theme IIIB 886:889 arg1 subgroups 856:864 three subgroups 850:864 three subgroups 850:864 Phylogenetic analysis showed that these AhXTHs, along with 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean, were classified into three subgroups: the I/II, IIIA and IIIB subclades. 35602895 7 40 theme IIIB 886:889 arg1 subclades 891:899 IIIA and IIIB subclades 877:899 IIIA and IIIB subclades 877:899 Phylogenetic analysis showed that these AhXTHs, along with 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean, were classified into three subgroups: the I/II, IIIA and IIIB subclades. 35602895 12 41 theme dried 1621:1625 arg1 seeds 1627:1631 dried seeds 1621:1631 dried seeds 1621:1631 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 3 42 theme seed 388:391 arg1 germination 393:403 seed germination 388:403 seed germination 388:403 Many genes are involved in the regulation of seed germination. 35602895 6 43 theme genes 671:675 arg1 total 653:657 a total 651:657 a total of 58 AhXTH genes 651:675 In this study, a total of 58 AhXTH genes were identified in the peanut genome. 35602895 0 44 theme Genome-wide 0:10 arg1 identification 12:25 Genome-wide identification 0:25 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut 0:100 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 5 45 theme gene 590:593 arg1 family 595:600 the XTH gene family 582:600 the XTH gene family in peanut 582:610 However, studies of the XTH gene family in peanut have not been reported. 35602895 12 46 theme expression 1780:1789 arg1 levels 1791:1796 relatively higher expression levels 1762:1796 relatively higher expression levels 1762:1796 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 9 47 theme conserved 1036:1044 arg1 patterns 1058:1065 relatively conserved exon-intron patterns 1025:1065 relatively conserved exon-intron patterns 1025:1065 07 and 17, and they had relatively conserved exon-intron patterns, most with three to four introns. 35602895 7 48 from Arabidopsis 789:799 arg1 AtXTHs 777:782 33 AtXTHs 774:782 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean 774:826 Phylogenetic analysis showed that these AhXTHs, along with 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean, were classified into three subgroups: the I/II, IIIA and IIIB subclades. 35602895 11 49 theme encoded 1389:1395 arg1 proteins 1397:1404 their encoded proteins 1383:1404 their encoded proteins 1383:1404 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 0 50 theme endotransglucosylase/hydrolase 41:70 arg1 members 84:90 xyloglucan endotransglucosylase/hydrolase gene family members 30:90 xyloglucan endotransglucosylase/hydrolase gene family members in peanut 30:100 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 10 51 theme segmental 1258:1266 arg1 duplications 1268:1279 segmental duplications 1258:1279 segmental duplications 1258:1279 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 0 52 theme family 77:82 arg1 members 84:90 xyloglucan endotransglucosylase/hydrolase gene family members 30:90 xyloglucan endotransglucosylase/hydrolase gene family members in peanut 30:100 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 12 53 theme family 1750:1755 arg1 % 1736:1736 45% 1734:1736 45% of the gene family 1734:1755 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 12 53 theme family 1750:1755 arg1 family 1750:1755 the gene family 1741:1755 the gene family 1741:1755 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 14 54 theme elongated 2178:2186 arg1 hypocotyls 2188:2197 elongated hypocotyls 2178:2197 elongated hypocotyls 2178:2197 The results of GUS histochemical staining showed that AhXTH4 was mainly expressed in germinated seeds and etiolated seedlings and had higher expression levels in elongated hypocotyls. 35602895 10 55 theme chromosomal 1109:1119 arg1 pattern 1134:1140 chromosomal distribution pattern 1109:1140 chromosomal distribution pattern 1109:1140 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 10 56 theme duplications 1268:1279 arg1 pairs 1249:1253 42 pairs 1246:1253 42 pairs of segmental duplications 1246:1279 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 10 56 theme duplications 1268:1279 arg1 pairs 1288:1292 23 pairs 1285:1292 23 pairs of tandem duplications 1285:1315 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 10 57 theme AhXTH 1186:1190 arg1 family 1192:1197 the AhXTH family 1182:1197 the AhXTH family 1182:1197 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 7 58 theme Phylogenetic 715:726 arg1 analysis 728:735 Phylogenetic analysis 715:735 Phylogenetic analysis 715:735 Phylogenetic analysis showed that these AhXTHs, along with 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean, were classified into three subgroups: the I/II, IIIA and IIIB subclades. 35602895 10 59 theme genome 1325:1330 arg1 evolution 1332:1340 genome evolution 1325:1340 genome evolution 1325:1340 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 14 60 theme expression 2157:2166 arg1 levels 2168:2173 higher expression levels 2150:2173 higher expression levels 2150:2173 The results of GUS histochemical staining showed that AhXTH4 was mainly expressed in germinated seeds and etiolated seedlings and had higher expression levels in elongated hypocotyls. 35602895 11 61 theme group 1558:1562 arg1 members 1538:1544 members 1538:1544 members of the same group 1538:1562 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 10 62 theme synteny 1146:1152 arg1 analysis 1154:1161 synteny analysis 1146:1161 synteny analysis 1146:1161 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 11 63 contain contained 1406:1414 arg2 sites 1470:1474 N-linked glycosylation sites 1447:1474 N-linked glycosylation sites 1447:1474 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 11 63 contain contained 1406:1414 arg2 domain 1436:1441 the conserved ExDxE domain 1416:1441 the conserved ExDxE domain 1416:1441 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 11 63 contain contained 1406:1414 arg1 proteins 1397:1404 their encoded proteins 1383:1404 their encoded proteins 1383:1404 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 11 64 theme conserved 1494:1502 arg1 loops 1525:1529 the conserved secondary structural loops 1-3 1490:1533 the conserved secondary structural loops 1-3 in members of the same group 1490:1562 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 10 65 theme tandem 1297:1302 arg1 duplications 1304:1315 tandem duplications 1297:1315 tandem duplications 1297:1315 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 2 66 theme emergence 293:301 arg1 consistency 269:279 the consistency 265:279 the consistency of seedling emergence 265:301 Improving the germination rate of seeds and the consistency of seedling emergence in the field could improve crop yields. 35602895 2 66 theme emergence 293:301 arg1 rate 247:250 the germination rate 231:250 the germination rate of seeds 231:259 Improving the germination rate of seeds and the consistency of seedling emergence in the field could improve crop yields. 35602895 2 67 theme crop 330:333 arg1 yields 335:340 crop yields 330:340 crop yields 330:340 Improving the germination rate of seeds and the consistency of seedling emergence in the field could improve crop yields. 35602895 1 68 theme plant 203:207 arg1 cycle 214:218 a new plant life cycle 197:218 a new plant life cycle 197:218 Seed germination marks the beginning of a new plant life cycle. 35602895 12 69 theme seed 1882:1885 arg1 germination 1887:1897 seed germination 1882:1897 seed germination 1882:1897 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 14 70 theme germinated 2101:2110 arg1 seeds 2112:2116 germinated seeds 2101:2116 germinated seeds 2101:2116 The results of GUS histochemical staining showed that AhXTH4 was mainly expressed in germinated seeds and etiolated seedlings and had higher expression levels in elongated hypocotyls. 35602895 7 71 dep subgroups 856:864 arg1 I/II 871:874 the I/II 867:874 the I/II 867:874 Phylogenetic analysis showed that these AhXTHs, along with 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean, were classified into three subgroups: the I/II, IIIA and IIIB subclades. 35602895 1 72 theme cycle 214:218 arg1 beginning 184:192 the beginning 180:192 the beginning of a new plant life cycle 180:218 Seed germination marks the beginning of a new plant life cycle. 35602895 12 73 theme Expression 1565:1574 arg1 analysis 1584:1591 Expression profile analysis 1565:1591 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data 1565:1684 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 11 74 link N-linked 1447:1454 arg1 sites 1470:1474 N-linked glycosylation sites 1447:1474 N-linked glycosylation sites 1447:1474 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 2 75 theme seeds 255:259 arg1 consistency 269:279 the consistency 265:279 the consistency of seedling emergence 265:301 Improving the germination rate of seeds and the consistency of seedling emergence in the field could improve crop yields. 35602895 2 75 theme seeds 255:259 arg1 rate 247:250 the germination rate 231:250 the germination rate of seeds 231:259 Improving the germination rate of seeds and the consistency of seedling emergence in the field could improve crop yields. 35602895 0 76 from peanut 95:100 arg1 profiles 123:130 their expression profiles 106:130 their expression profiles during seed germination 106:154 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 0 76 from peanut 95:100 arg1 identification 12:25 Genome-wide identification 0:25 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut 0:100 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 11 77 theme ExDxE 1430:1434 arg1 domain 1436:1441 the conserved ExDxE domain 1416:1441 the conserved ExDxE domain 1416:1441 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 11 78 theme structural 1514:1523 arg1 loops 1525:1529 the conserved secondary structural loops 1-3 1490:1533 the conserved secondary structural loops 1-3 in members of the same group 1490:1562 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 15 79 theme seed 2292:2295 arg1 germination 2297:2307 seed germination 2292:2307 seed germination 2292:2307 AhXTH4 was also verified to play a crucial role in the cell elongation of hypocotyls during seed germination. 35602895 1 80 theme Seed 157:160 arg1 germination 162:172 Seed germination 157:172 Seed germination 157:172 Seed germination marks the beginning of a new plant life cycle. 35602895 12 81 theme germinated 1644:1653 arg1 seeds 1655:1659 newly germinated seeds 1638:1659 newly germinated seeds using transcriptome data 1638:1684 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 4 82 theme peanut 441:446 arg1 XTHs 448:451 some peanut XTHs 436:451 some peanut XTHs (xyloglucan endotransglucosylases/hydrolases) 436:497 Our previous study found that some peanut XTHs (xyloglucan endotransglucosylases/hydrolases) were expressed at higher levels at the newly germinated stage. 35602895 4 82 theme peanut 441:446 arg1 endotransglucosylases/hydrolases 465:496 xyloglucan endotransglucosylases/hydrolases 454:496 xyloglucan endotransglucosylases/hydrolases 454:496 Our previous study found that some peanut XTHs (xyloglucan endotransglucosylases/hydrolases) were expressed at higher levels at the newly germinated stage. 35602895 15 83 theme hypocotyls 2274:2283 arg1 elongation 2260:2269 the cell elongation 2251:2269 the cell elongation of hypocotyls during seed germination 2251:2307 AhXTH4 was also verified to play a crucial role in the cell elongation of hypocotyls during seed germination. 35602895 5 84 from studies 571:577 arg1 peanut 605:610 peanut 605:610 peanut 605:610 However, studies of the XTH gene family in peanut have not been reported. 35602895 15 85 theme cell 2255:2258 arg1 elongation 2260:2269 the cell elongation 2251:2269 the cell elongation of hypocotyls during seed germination 2251:2307 AhXTH4 was also verified to play a crucial role in the cell elongation of hypocotyls during seed germination. 35602895 11 86 theme glycosylation 1456:1468 arg1 sites 1470:1474 N-linked glycosylation sites 1447:1474 N-linked glycosylation sites 1447:1474 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 13 87 theme seed 1998:2001 arg1 germination 2003:2013 seed germination 1998:2013 seed germination 1998:2013 The results of quantitative real-time PCR also confirmed that some AhXTHs were upregulated during seed germination. 35602895 12 88 theme seeds 1627:1631 arg1 analysis 1584:1591 Expression profile analysis 1565:1591 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data 1565:1684 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 0 89 from identification 12:25 arg1 peanut 95:100 peanut 95:100 peanut 95:100 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 0 90 from members 84:90 arg1 peanut 95:100 peanut 95:100 peanut 95:100 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 14 91 theme histochemical 2035:2047 arg1 staining 2049:2056 GUS histochemical staining 2031:2056 GUS histochemical staining 2031:2056 The results of GUS histochemical staining showed that AhXTH4 was mainly expressed in germinated seeds and etiolated seedlings and had higher expression levels in elongated hypocotyls. 35602895 10 92 theme replication 1216:1226 arg1 pairs 1249:1253 42 pairs 1246:1253 42 pairs of segmental duplications 1246:1279 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 10 92 theme replication 1216:1226 arg1 pairs 1288:1292 23 pairs 1285:1292 23 pairs of tandem duplications 1285:1315 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 10 92 theme replication 1216:1226 arg1 events 1228:1233 many replication events 1211:1233 many replication events 1211:1233 Through chromosomal distribution pattern and synteny analysis, it was found that the AhXTH family experienced many replication events, including 42 pairs of segmental duplications and 23 pairs of tandem duplications, during genome evolution. 35602895 0 93 theme seed 139:142 arg1 germination 144:154 seed germination 139:154 seed germination 139:154 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 8 94 theme chr 996:998 arg1 exception 983:991 the exception 979:991 the exception of chr 979:998 All AhXTH genes were unevenly distributed on the 18 peanut chromosomes, with the exception of chr. 35602895 12 95 theme harvested 1604:1612 arg1 seeds 1614:1618 freshly harvested seeds 1596:1618 freshly harvested seeds 1596:1618 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 11 96 theme motif 1353:1357 arg1 analysis 1359:1366 Conserved motif analysis 1343:1366 Conserved motif analysis 1343:1366 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 5 97 theme XTH 586:588 arg1 family 595:600 the XTH gene family 582:600 the XTH gene family in peanut 582:610 However, studies of the XTH gene family in peanut have not been reported. 35602895 3 98 theme germination 393:403 arg1 regulation 374:383 the regulation 370:383 the regulation of seed germination 370:403 Many genes are involved in the regulation of seed germination. 35602895 12 99 theme germination 1810:1820 arg1 stage 1822:1826 the seed germination stage 1801:1826 the seed germination stage 1801:1826 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 6 100 theme AhXTH 665:669 arg1 genes 671:675 58 AhXTH genes 662:675 58 AhXTH genes 662:675 In this study, a total of 58 AhXTH genes were identified in the peanut genome. 35602895 0 101 theme xyloglucan 30:39 arg1 members 84:90 xyloglucan endotransglucosylase/hydrolase gene family members 30:90 xyloglucan endotransglucosylase/hydrolase gene family members in peanut 30:100 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 5 102 theme family 595:600 arg1 studies 571:577 studies 571:577 studies of the XTH gene family in peanut 571:610 However, studies of the XTH gene family in peanut have not been reported. 35602895 12 103 theme profile 1576:1582 arg1 analysis 1584:1591 Expression profile analysis 1565:1591 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data 1565:1684 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 0 104 theme gene 72:75 arg1 members 84:90 xyloglucan endotransglucosylase/hydrolase gene family members 30:90 xyloglucan endotransglucosylase/hydrolase gene family members in peanut 30:100 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 4 105 theme germinated 544:553 arg1 stage 555:559 the newly germinated stage 534:559 the newly germinated stage 534:559 Our previous study found that some peanut XTHs (xyloglucan endotransglucosylases/hydrolases) were expressed at higher levels at the newly germinated stage. 35602895 9 106 theme exon-intron 1046:1056 arg1 patterns 1058:1065 relatively conserved exon-intron patterns 1025:1065 relatively conserved exon-intron patterns 1025:1065 07 and 17, and they had relatively conserved exon-intron patterns, most with three to four introns. 35602895 0 107 theme members 84:90 arg1 profiles 123:130 their expression profiles 106:130 their expression profiles during seed germination 106:154 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 0 107 theme members 84:90 arg1 identification 12:25 Genome-wide identification 0:25 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut 0:100 Genome-wide identification of xyloglucan endotransglucosylase/hydrolase gene family members in peanut and their expression profiles during seed germination. 35602895 13 108 theme quantitative 1915:1926 arg1 PCR 1938:1940 quantitative real-time PCR 1915:1940 quantitative real-time PCR 1915:1940 The results of quantitative real-time PCR also confirmed that some AhXTHs were upregulated during seed germination. 35602895 7 109 from GmXTHs 808:813 arg1 AtXTHs 777:782 33 AtXTHs 774:782 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean 774:826 Phylogenetic analysis showed that these AhXTHs, along with 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean, were classified into three subgroups: the I/II, IIIA and IIIB subclades. 35602895 12 110 theme higher 1773:1778 arg1 levels 1791:1796 relatively higher expression levels 1762:1796 relatively higher expression levels 1762:1796 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 12 111 theme gene 1745:1748 arg1 family 1750:1755 the gene family 1741:1755 the gene family 1741:1755 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 11 112 theme same 1553:1556 arg1 group 1558:1562 the same group 1549:1562 the same group 1549:1562 Conserved motif analysis indicated that their encoded proteins contained the conserved ExDxE domain and N-linked glycosylation sites and displayed the conserved secondary structural loops 1-3 in members of the same group. 35602895 7 113 from soybean 820:826 arg1 Arabidopsis 789:799 Arabidopsis 789:799 Arabidopsis 789:799 Phylogenetic analysis showed that these AhXTHs, along with 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean, were classified into three subgroups: the I/II, IIIA and IIIB subclades. 35602895 7 113 from soybean 820:826 arg1 GmXTHs 808:813 61 GmXTHs 805:813 61 GmXTHs 805:813 Phylogenetic analysis showed that these AhXTHs, along with 33 AtXTHs from Arabidopsis and 61 GmXTHs from soybean, were classified into three subgroups: the I/II, IIIA and IIIB subclades. 35602895 12 114 contain had 1758:1760 arg1 genes 1709:1713 26 AhXTH genes 1700:1713 26 AhXTH genes 1700:1713 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 12 114 contain had 1758:1760 arg2 levels 1791:1796 relatively higher expression levels 1762:1796 relatively higher expression levels 1762:1796 Expression profile analysis of freshly harvested seeds, dried seeds, and newly germinated seeds using transcriptome data revealed that 26 AhXTH genes, which account for 45% of the gene family, had relatively higher expression levels at the seed germination stage, implying the important roles of AhXTHs in regulating seed germination. 35602895 6 115 theme peanut 700:705 arg1 genome 707:712 the peanut genome 696:712 the peanut genome 696:712 In this study, a total of 58 AhXTH genes were identified in the peanut genome. 35145548 0 0 theme Pediatric 67:75 arg1 Patients 77:84 Six Chinese Pediatric Patients 55:84 Six Chinese Pediatric Patients 55:84 Further Delineation of the Spectrum of XMEN Disease in Six Chinese Pediatric Patients. 35145548 4 1 from microbes 602:609 arg1 patients 614:621 patients 614:621 patients 614:621 Medical records were retrieved, immunological phenotypes were assessed, and infectious microbes in patients were detected. 35145548 5 2 theme male 642:645 arg1 patients 647:654 Six male patients 638:654 Six male patients (mean age, 6.3 years) from five unrelated families 638:705 Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. 35145548 5 2 theme male 642:645 arg1 XMEN 737:740 XMEN 737:740 XMEN 737:740 Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. 35145548 11 3 theme Chinese 1366:1372 arg1 patients 1374:1381 Chinese patients 1366:1381 Chinese patients with XMEN 1366:1391 This study reports the clinical and molecular features of Chinese patients with XMEN. 35145548 1 4 theme loss-of-function 249:264 arg1 variants 266:273 loss-of-function variants 249:273 loss-of-function variants in the MAGT1 gene 249:291 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 0 5 theme Chinese 59:65 arg1 Patients 77:84 Six Chinese Pediatric Patients 55:84 Six Chinese Pediatric Patients 55:84 Further Delineation of the Spectrum of XMEN Disease in Six Chinese Pediatric Patients. 35145548 0 6 from Delineation 8:18 arg1 Patients 77:84 Six Chinese Pediatric Patients 55:84 Six Chinese Pediatric Patients 55:84 Further Delineation of the Spectrum of XMEN Disease in Six Chinese Pediatric Patients. 35145548 6 7 theme liver 802:806 arg1 enzymes 808:814 elevated liver enzymes 793:814 elevated liver enzymes 793:814 Five patients presented with a major complaint of elevated liver enzymes, while one patient was referred for recurrent fever, cough and skin rash. 35145548 1 8 theme N-linked 164:171 arg1 glycosylation 173:185 N-linked glycosylation 164:185 N-linked glycosylation 164:185 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 10 9 theme pathogenic 1238:1247 arg1 microbes 1249:1256 No pathogenic microbes 1235:1256 No pathogenic microbes other than EBV 1235:1271 No pathogenic microbes other than EBV were identified in these patients. 35145548 5 10 from families 698:705 arg1 patients 647:654 Six male patients 638:654 Six male patients (mean age, 6.3 years) from five unrelated families 638:705 Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. 35145548 5 10 from families 698:705 arg1 XMEN 737:740 XMEN 737:740 XMEN 737:740 Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. 35145548 9 11 theme CD4/CD8 1198:1204 arg1 ratios 1206:1211 inverted CD4/CD8 ratios 1189:1211 inverted CD4/CD8 ratios 1189:1211 Immune phenotypes included CD4 T-cell lymphopenia, elevated B cells, inverted CD4/CD8 ratios, and elevated αβDNTs. 35145548 2 12 from family 321:326 arg1 patients 303:310 Only two patients 294:310 Only two patients from one family 294:326 Only two patients from one family have been diagnosed with XMEN in China. 35145548 1 13 dep EBV-infection 146:158 arg1 disease 201:207 defect (XMEN) disease 187:207 defect (XMEN) disease 187:207 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 9 14 theme CD4 1147:1149 arg1 lymphopenia 1158:1168 CD4 T-cell lymphopenia 1147:1168 CD4 T-cell lymphopenia 1147:1168 Immune phenotypes included CD4 T-cell lymphopenia, elevated B cells, inverted CD4/CD8 ratios, and elevated αβDNTs. 35145548 12 15 theme transaminase 1412:1423 arg1 elevation 1425:1433 transaminase elevation 1412:1433 transaminase elevation 1412:1433 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 35145548 5 16 theme mean 657:660 arg1 6.3 years 667:675 6.3 years 667:675 6.3 years 667:675 Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. 35145548 5 16 theme mean 657:660 arg1 age 662:664 mean age 657:664 mean age 657:664 Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. 35145548 8 17 from tissues 1022:1028 arg1 findings 995:1002 Histopathological findings 977:1002 Histopathological findings from liver biopsy tissues 977:1028 Histopathological findings from liver biopsy tissues showed variable hepatic steatosis, fibrosis, inflammatory infiltration, and glycogenosis. 35145548 11 18 theme patients 1374:1381 arg1 features 1354:1361 the clinical and molecular features 1327:1361 the clinical and molecular features of Chinese patients with XMEN 1327:1391 This study reports the clinical and molecular features of Chinese patients with XMEN. 35145548 8 19 theme variable 1037:1044 arg1 steatosis 1054:1062 variable hepatic steatosis 1037:1062 variable hepatic steatosis 1037:1062 Histopathological findings from liver biopsy tissues showed variable hepatic steatosis, fibrosis, inflammatory infiltration, and glycogenosis. 35145548 8 20 theme biopsy 1015:1020 arg1 tissues 1022:1028 liver biopsy tissues 1009:1028 liver biopsy tissues 1009:1028 Histopathological findings from liver biopsy tissues showed variable hepatic steatosis, fibrosis, inflammatory infiltration, and glycogenosis. 35145548 2 21 from XMEN 353:356 arg1 China 361:365 China 361:365 China 361:365 Only two patients from one family have been diagnosed with XMEN in China. 35145548 1 22 theme defect 187:192 arg1 disease 201:207 defect (XMEN) disease 187:207 defect (XMEN) disease 187:207 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 9 23 theme inverted 1189:1196 arg1 ratios 1206:1211 inverted CD4/CD8 ratios 1189:1211 inverted CD4/CD8 ratios 1189:1211 Immune phenotypes included CD4 T-cell lymphopenia, elevated B cells, inverted CD4/CD8 ratios, and elevated αβDNTs. 35145548 6 24 theme recurrent 852:860 arg1 fever 862:866 recurrent fever 852:866 recurrent fever 852:866 Five patients presented with a major complaint of elevated liver enzymes, while one patient was referred for recurrent fever, cough and skin rash. 35145548 1 25 with deficiency 102:111 arg1 susceptibility 128:141 increased susceptibility 118:141 increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease 118:207 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 7 26 theme EBV 914:916 arg1 viremia 918:924 EBV viremia 914:924 EBV viremia 914:924 Five patients developed EBV viremia, and one patient developed non-Hodgkin's lymphoma. 35145548 9 27 theme B 1180:1180 arg1 cells 1182:1186 elevated B cells 1171:1186 elevated B cells 1171:1186 Immune phenotypes included CD4 T-cell lymphopenia, elevated B cells, inverted CD4/CD8 ratios, and elevated αβDNTs. 35145548 0 28 theme Further 0:6 arg1 Delineation 8:18 Further Delineation 0:18 Further Delineation of the Spectrum of XMEN Disease in Six Chinese Pediatric Patients. 0:85 Further Delineation of the Spectrum of XMEN Disease in Six Chinese Pediatric Patients. 35145548 1 29 theme MAGT1 282:286 arg1 gene 288:291 the MAGT1 gene 278:291 the MAGT1 gene 278:291 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 8 30 theme hepatic 1046:1052 arg1 steatosis 1054:1062 variable hepatic steatosis 1037:1062 variable hepatic steatosis 1037:1062 Histopathological findings from liver biopsy tissues showed variable hepatic steatosis, fibrosis, inflammatory infiltration, and glycogenosis. 35145548 12 31 theme chronic 1436:1442 arg1 infection 1448:1456 chronic EBV infection 1436:1456 chronic EBV infection 1436:1456 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 35145548 12 32 theme lymphoproliferative 1477:1495 arg1 disease 1497:1503 EBV-associated lymphoproliferative disease 1462:1503 EBV-associated lymphoproliferative disease 1462:1503 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 35145548 1 33 theme XMEN 195:198 arg1 disease 201:207 defect (XMEN) disease 187:207 defect (XMEN) disease 187:207 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 8 34 theme Histopathological 977:993 arg1 findings 995:1002 Histopathological findings 977:1002 Histopathological findings from liver biopsy tissues 977:1028 Histopathological findings from liver biopsy tissues showed variable hepatic steatosis, fibrosis, inflammatory infiltration, and glycogenosis. 35145548 1 35 theme X-linked 87:94 arg1 deficiency 102:111 X-linked MAGT1 deficiency 87:111 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease 87:207 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 1 35 theme X-linked 87:94 arg1 immunodeficiency 222:237 a primary immunodeficiency 212:237 a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene 212:291 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 9 36 theme elevated 1171:1178 arg1 cells 1182:1186 elevated B cells 1171:1186 elevated B cells 1171:1186 Immune phenotypes included CD4 T-cell lymphopenia, elevated B cells, inverted CD4/CD8 ratios, and elevated αβDNTs. 35145548 3 37 theme immunological 438:450 arg1 characteristics 452:466 the genetic, clinical, and immunological characteristics 411:466 the genetic, clinical, and immunological characteristics of six pediatric patients 411:492 In this study, we retrospectively analyzed the genetic, clinical, and immunological characteristics of six pediatric patients in a Chinese cohort. 35145548 5 38 dep patients 647:654 arg1 6.3 years 667:675 6.3 years 667:675 6.3 years 667:675 Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. 35145548 5 38 dep patients 647:654 arg1 age 662:664 mean age 657:664 mean age 657:664 Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. 35145548 1 39 link N-linked 164:171 arg1 glycosylation 173:185 N-linked glycosylation 164:185 N-linked glycosylation 164:185 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 1 40 theme MAGT1 96:100 arg1 deficiency 102:111 X-linked MAGT1 deficiency 87:111 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease 87:207 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 1 40 theme MAGT1 96:100 arg1 immunodeficiency 222:237 a primary immunodeficiency 212:237 a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene 212:291 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 11 41 theme molecular 1344:1352 arg1 features 1354:1361 the clinical and molecular features 1327:1361 the clinical and molecular features of Chinese patients with XMEN 1327:1391 This study reports the clinical and molecular features of Chinese patients with XMEN. 35145548 4 42 theme immunological 547:559 arg1 phenotypes 561:570 immunological phenotypes 547:570 immunological phenotypes 547:570 Medical records were retrieved, immunological phenotypes were assessed, and infectious microbes in patients were detected. 35145548 5 43 theme unrelated 688:696 arg1 families 698:705 five unrelated families 683:705 five unrelated families 683:705 Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. 35145548 9 44 theme elevated 1218:1225 arg1 αβDNTs 1227:1232 elevated αβDNTs 1218:1232 elevated αβDNTs 1218:1232 Immune phenotypes included CD4 T-cell lymphopenia, elevated B cells, inverted CD4/CD8 ratios, and elevated αβDNTs. 35145548 3 45 theme genetic 415:421 arg1 characteristics 452:466 the genetic, clinical, and immunological characteristics 411:466 the genetic, clinical, and immunological characteristics of six pediatric patients 411:492 In this study, we retrospectively analyzed the genetic, clinical, and immunological characteristics of six pediatric patients in a Chinese cohort. 35145548 0 46 theme Spectrum 27:34 arg1 Delineation 8:18 Further Delineation 0:18 Further Delineation of the Spectrum of XMEN Disease in Six Chinese Pediatric Patients. 0:85 Further Delineation of the Spectrum of XMEN Disease in Six Chinese Pediatric Patients. 35145548 4 47 theme Medical 515:521 arg1 records 523:529 Medical records 515:529 Medical records 515:529 Medical records were retrieved, immunological phenotypes were assessed, and infectious microbes in patients were detected. 35145548 1 48 from variants 266:273 arg1 gene 288:291 the MAGT1 gene 278:291 the MAGT1 gene 278:291 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 12 49 theme XMEN 1525:1528 arg1 possibility 1510:1520 the possibility 1506:1520 the possibility of XMEN 1506:1528 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 35145548 0 50 theme Disease 44:50 arg1 Spectrum 27:34 the Spectrum 23:34 the Spectrum of XMEN Disease 23:50 Further Delineation of the Spectrum of XMEN Disease in Six Chinese Pediatric Patients. 35145548 9 51 theme Immune 1120:1125 arg1 phenotypes 1127:1136 Immune phenotypes 1120:1136 Immune phenotypes 1120:1136 Immune phenotypes included CD4 T-cell lymphopenia, elevated B cells, inverted CD4/CD8 ratios, and elevated αβDNTs. 35145548 3 52 theme pediatric 475:483 arg1 patients 485:492 six pediatric patients 471:492 six pediatric patients 471:492 In this study, we retrospectively analyzed the genetic, clinical, and immunological characteristics of six pediatric patients in a Chinese cohort. 35145548 0 53 theme XMEN 39:42 arg1 Disease 44:50 XMEN Disease 39:50 XMEN Disease 39:50 Further Delineation of the Spectrum of XMEN Disease in Six Chinese Pediatric Patients. 35145548 6 54 theme skin 879:882 arg1 rash 884:887 skin rash 879:887 skin rash 879:887 Five patients presented with a major complaint of elevated liver enzymes, while one patient was referred for recurrent fever, cough and skin rash. 35145548 12 55 theme EBV-associated 1462:1475 arg1 disease 1497:1503 EBV-associated lymphoproliferative disease 1462:1503 EBV-associated lymphoproliferative disease 1462:1503 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 35145548 3 56 theme patients 485:492 arg1 characteristics 452:466 the genetic, clinical, and immunological characteristics 411:466 the genetic, clinical, and immunological characteristics of six pediatric patients 411:492 In this study, we retrospectively analyzed the genetic, clinical, and immunological characteristics of six pediatric patients in a Chinese cohort. 35145548 12 57 with patients 1398:1405 arg1 elevation 1425:1433 transaminase elevation 1412:1433 transaminase elevation 1412:1433 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 35145548 12 57 with patients 1398:1405 arg1 disease 1497:1503 EBV-associated lymphoproliferative disease 1462:1503 EBV-associated lymphoproliferative disease 1462:1503 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 35145548 12 57 with patients 1398:1405 arg1 infection 1448:1456 chronic EBV infection 1436:1456 chronic EBV infection 1436:1456 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 35145548 8 58 theme inflammatory 1075:1086 arg1 infiltration 1088:1099 inflammatory infiltration 1075:1099 inflammatory infiltration 1075:1099 Histopathological findings from liver biopsy tissues showed variable hepatic steatosis, fibrosis, inflammatory infiltration, and glycogenosis. 35145548 6 59 theme major 774:778 arg1 complaint 780:788 a major complaint 772:788 a major complaint of elevated liver enzymes 772:814 Five patients presented with a major complaint of elevated liver enzymes, while one patient was referred for recurrent fever, cough and skin rash. 35145548 6 60 theme elevated 793:800 arg1 enzymes 808:814 elevated liver enzymes 793:814 elevated liver enzymes 793:814 Five patients presented with a major complaint of elevated liver enzymes, while one patient was referred for recurrent fever, cough and skin rash. 35145548 1 61 theme increased 118:126 arg1 susceptibility 128:141 increased susceptibility 118:141 increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease 118:207 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 1 62 theme primary 214:220 arg1 deficiency 102:111 X-linked MAGT1 deficiency 87:111 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease 87:207 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 1 62 theme primary 214:220 arg1 immunodeficiency 222:237 a primary immunodeficiency 212:237 a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene 212:291 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 7 63 theme non-Hodgkin 953:963 arg1 lymphoma 967:974 non-Hodgkin's lymphoma 953:974 non-Hodgkin's lymphoma 953:974 Five patients developed EBV viremia, and one patient developed non-Hodgkin's lymphoma. 35145548 4 64 theme infectious 591:600 arg1 microbes 602:609 infectious microbes 591:609 infectious microbes in patients 591:621 Medical records were retrieved, immunological phenotypes were assessed, and infectious microbes in patients were detected. 35145548 1 65 link X-linked 87:94 arg1 deficiency 102:111 X-linked MAGT1 deficiency 87:111 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease 87:207 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 1 65 link X-linked 87:94 arg1 immunodeficiency 222:237 a primary immunodeficiency 212:237 a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene 212:291 X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. 35145548 6 66 theme enzymes 808:814 arg1 complaint 780:788 a major complaint 772:788 a major complaint of elevated liver enzymes 772:814 Five patients presented with a major complaint of elevated liver enzymes, while one patient was referred for recurrent fever, cough and skin rash. 35145548 11 67 with patients 1374:1381 arg1 XMEN 1388:1391 XMEN 1388:1391 XMEN 1388:1391 This study reports the clinical and molecular features of Chinese patients with XMEN. 35145548 9 68 theme T-cell 1151:1156 arg1 lymphopenia 1158:1168 CD4 T-cell lymphopenia 1147:1168 CD4 T-cell lymphopenia 1147:1168 Immune phenotypes included CD4 T-cell lymphopenia, elevated B cells, inverted CD4/CD8 ratios, and elevated αβDNTs. 35145548 3 69 theme Chinese 499:505 arg1 cohort 507:512 a Chinese cohort 497:512 a Chinese cohort 497:512 In this study, we retrospectively analyzed the genetic, clinical, and immunological characteristics of six pediatric patients in a Chinese cohort. 35145548 3 70 theme clinical 424:431 arg1 characteristics 452:466 the genetic, clinical, and immunological characteristics 411:466 the genetic, clinical, and immunological characteristics of six pediatric patients 411:492 In this study, we retrospectively analyzed the genetic, clinical, and immunological characteristics of six pediatric patients in a Chinese cohort. 35145548 12 71 theme liver 1575:1579 arg1 diseases 1581:1588 isolated liver diseases 1566:1588 isolated liver diseases 1566:1588 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 35145548 11 72 theme clinical 1331:1338 arg1 features 1354:1361 the clinical and molecular features 1327:1361 the clinical and molecular features of Chinese patients with XMEN 1327:1391 This study reports the clinical and molecular features of Chinese patients with XMEN. 35145548 12 73 theme EBV 1444:1446 arg1 infection 1448:1456 chronic EBV infection 1436:1456 chronic EBV infection 1436:1456 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 35145548 8 74 theme liver 1009:1013 arg1 tissues 1022:1028 liver biopsy tissues 1009:1028 liver biopsy tissues 1009:1028 Histopathological findings from liver biopsy tissues showed variable hepatic steatosis, fibrosis, inflammatory infiltration, and glycogenosis. 35145548 10 75 theme other 1258:1262 arg1 microbes 1249:1256 No pathogenic microbes 1235:1256 No pathogenic microbes other than EBV 1235:1271 No pathogenic microbes other than EBV were identified in these patients. 35145548 12 76 theme isolated 1566:1573 arg1 diseases 1581:1588 isolated liver diseases 1566:1588 isolated liver diseases 1566:1588 For patients with transaminase elevation, chronic EBV infection and EBV-associated lymphoproliferative disease, the possibility of XMEN should be considered in addition to isolated liver diseases. 36688652 8 0 from -6B 1339:1341 arg1 proteins 1314:1321 U20 proteins 1310:1321 U20 proteins from HHV-6A and -6B 1310:1341 Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. 36688652 3 1 theme HHV6B 605:609 arg1 product 620:626 the HHV6B U20 gene product 601:626 the HHV6B U20 gene product 601:626 Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. 36688652 8 2 theme HHV6A 1409:1413 arg1 U20 1415:1417 HHV6A U20 1409:1417 HHV6A U20 1409:1417 Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. 36688652 4 3 link N-linked 816:823 arg1 glycans 825:831 its N-linked glycans 812:831 its N-linked glycans 812:831 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 2 4 theme host 496:499 arg1 defenses 501:508 host defenses 496:508 host defenses 496:508 As such, these viruses are among the most pervasive and stealthy of all viruses; they must necessarily excel at escaping immune detection throughout the life of the host, and yet, very little is known about how these viruses so successfully escape host defenses. 36688652 4 5 theme surface-expressed 848:864 arg1 glycoproteins 866:878 surface-expressed glycoproteins 848:878 surface-expressed glycoproteins 848:878 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 7 6 theme class 1228:1232 arg1 complex 1261:1267 class I major histocompatibility complex 1228:1267 class I major histocompatibility complex (MHC) 1228:1273 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 6 theme class 1228:1232 arg1 MHC 1270:1272 MHC 1270:1272 MHC 1270:1272 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 4 7 theme several 769:775 arg1 modifications 795:807 several posttranslational modifications 769:807 several posttranslational modifications 769:807 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 10 8 theme HHV6B 2047:2051 arg1 U20 2053:2055 HHV6B U20 2047:2055 HHV6B U20 2047:2055 Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and posttranslational modifications occurring on HHV6B U20. 36688652 9 9 with infection 1597:1605 arg1 K. 1635:1636 K. 1635:1636 K. 1635:1636 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 9 9 with infection 1597:1605 arg1 M. 1651:1652 M. 1651:1652 M. 1651:1652 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 9 9 with infection 1597:1605 arg1 Jensen 1675:1680 Jensen 1675:1680 Jensen 1675:1680 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 9 9 with infection 1597:1605 arg1 Virol 1693:1697 Virol 1693:1697 Virol 1693:1697 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 9 9 with infection 1597:1605 arg1 D. 1669:1670 D. 1669:1670 D. 1669:1670 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 3 10 theme product 620:626 arg1 expression 537:546 expression 537:546 expression 537:546 Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. 36688652 3 10 theme product 620:626 arg1 modifications 584:596 posttranslational modifications 566:596 posttranslational modifications 566:596 Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. 36688652 3 10 theme product 620:626 arg1 trafficking 549:559 trafficking 549:559 trafficking 549:559 Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. 36688652 9 11 theme tumor 1522:1526 arg1 apoptosis 1566:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis 1522:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799) 1522:1887 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 1 12 theme human 65:69 arg1 [HHV-6A 86:92 human herpesvirus 6A [HHV-6A] 65:93 human herpesvirus 6A [HHV-6A] 65:93 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 1 12 theme human 65:69 arg1 Roseoloviruses 49:62 Roseoloviruses 49:62 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) 49:107 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 10 13 theme biological 1919:1928 arg1 characterization 1946:1961 cell biological and biochemical characterization 1914:1961 cell biological and biochemical characterization of the trafficking 1914:1980 Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and posttranslational modifications occurring on HHV6B U20. 36688652 9 14 theme necrosis 1528:1535 arg1 apoptosis 1566:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis 1522:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799) 1522:1887 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 7 15 theme membrane 1194:1201 arg1 IMPORTANCE 1126:1135 IMPORTANCE 1126:1135 IMPORTANCE The roseolovirus U20 proteins 1126:1165 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 15 theme membrane 1194:1201 arg1 glycoproteins 1203:1215 virus-encoded integral membrane glycoproteins 1171:1215 virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds 1171:1284 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 1 16 theme herpesvirus 71:81 arg1 [HHV-6A 86:92 human herpesvirus 6A [HHV-6A] 65:93 human herpesvirus 6A [HHV-6A] 65:93 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 1 16 theme herpesvirus 71:81 arg1 Roseoloviruses 49:62 Roseoloviruses 49:62 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) 49:107 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 7 17 dep -like 1274:1278 arg1 folds 1280:1284 folds 1280:1284 folds 1280:1284 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 2 18 theme viruses 320:326 arg1 pervasive 290:298 pervasive 290:298 pervasive 290:298 As such, these viruses are among the most pervasive and stealthy of all viruses; they must necessarily excel at escaping immune detection throughout the life of the host, and yet, very little is known about how these viruses so successfully escape host defenses. 36688652 4 19 theme glycoproteins 866:878 arg1 indicative 834:843 indicative 834:843 indicative 834:843 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 3 20 theme U20 611:613 arg1 product 620:626 the HHV6B U20 gene product 601:626 the HHV6B U20 gene product 601:626 Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. 36688652 9 21 theme factor 1537:1542 arg1 apoptosis 1566:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis 1522:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799) 1522:1887 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 9 22 theme HHV6B 1491:1495 arg1 U20 1497:1499 HHV6B U20 1491:1499 HHV6B U20 1491:1499 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 2 23 dep pervasive 290:298 arg1 the 281:283 the 281:283 the 281:283 As such, these viruses are among the most pervasive and stealthy of all viruses; they must necessarily excel at escaping immune detection throughout the life of the host, and yet, very little is known about how these viruses so successfully escape host defenses. 36688652 1 24 theme human 128:132 arg1 population 134:143 the human population 124:143 the human population 124:143 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 2 25 theme immune 369:374 arg1 detection 376:384 immune detection 369:384 immune detection 369:384 As such, these viruses are among the most pervasive and stealthy of all viruses; they must necessarily excel at escaping immune detection throughout the life of the host, and yet, very little is known about how these viruses so successfully escape host defenses. 36688652 3 26 theme gene 615:618 arg1 product 620:626 the HHV6B U20 gene product 601:626 the HHV6B U20 gene product 601:626 Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. 36688652 4 27 theme secretory 741:749 arg1 system 751:756 the secretory system 737:756 the secretory system 737:756 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 9 28 theme alpha 1544:1548 arg1 apoptosis 1566:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis 1522:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799) 1522:1887 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 1 29 theme population 134:143 arg1 population 134:143 the human population 124:143 the human population 124:143 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 1 29 theme population 134:143 arg1 % 119:119 >90% 116:119 >90% of the human population 116:143 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 9 30 theme -induced 1557:1564 arg1 apoptosis 1566:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis 1522:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799) 1522:1887 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 6 31 theme host 1111:1114 arg1 defenses 1116:1123 host defenses 1111:1123 host defenses 1111:1123 These results provide a framework to understand the role(s) of U20 in evading host defenses. 36688652 7 32 gly glycoproteins 1203:1215 arg1 IMPORTANCE 1126:1135 IMPORTANCE 1126:1135 IMPORTANCE The roseolovirus U20 proteins 1126:1165 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 32 gly glycoproteins 1203:1215 arg1 glycoproteins 1203:1215 virus-encoded integral membrane glycoproteins 1171:1215 virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds 1171:1284 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 8 33 from HHV-6A 1328:1333 arg1 proteins 1314:1321 U20 proteins 1310:1321 U20 proteins from HHV-6A and -6B 1310:1341 Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. 36688652 0 34 theme HHV-6B 24:29 arg1 Immunoevasin 35:46 the HHV-6B U20 Immunoevasin 20:46 the HHV-6B U20 Immunoevasin 20:46 Characterization of the HHV-6B U20 Immunoevasin. 36688652 8 35 theme HHV6B 1423:1427 arg1 U20 1429:1431 HHV6B U20 1423:1431 HHV6B U20 1423:1431 Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. 36688652 9 36 theme TNF-α 1551:1555 arg1 apoptosis 1566:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis 1522:1574 tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799) 1522:1887 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 4 37 gly glycoproteins 866:878 arg1 glycoproteins 866:878 surface-expressed glycoproteins 848:878 surface-expressed glycoproteins 848:878 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 7 38 dep glycoproteins 1203:1215 arg1 -like 1274:1278 -like 1274:1278 -like 1274:1278 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 1 39 theme early 152:156 arg1 childhood 158:166 early childhood 152:166 early childhood 152:166 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 10 40 theme posttranslational 2002:2018 arg1 modifications 2020:2032 posttranslational modifications 2002:2032 posttranslational modifications occurring on HHV6B U20 2002:2055 Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and posttranslational modifications occurring on HHV6B U20. 36688652 5 41 theme Tyr 1020:1022 arg1 residue 1024:1030 Tyr residue 1020:1030 Tyr residue 1020:1030 Interestingly, U20 is also phosphorylated on at least one Ser, Thr, or Tyr residue. 36688652 4 42 theme N-linked 816:823 arg1 glycans 825:831 its N-linked glycans 812:831 its N-linked glycans 812:831 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 7 43 dep IMPORTANCE 1126:1135 arg1 proteins 1158:1165 The roseolovirus U20 proteins 1137:1165 IMPORTANCE The roseolovirus U20 proteins 1126:1165 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 10 44 theme biochemical 1934:1944 arg1 characterization 1946:1961 cell biological and biochemical characterization 1914:1961 cell biological and biochemical characterization of the trafficking 1914:1980 Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and posttranslational modifications occurring on HHV6B U20. 36688652 1 45 dep Roseoloviruses 49:62 arg1 -7 105:106 -7 105:106 -7 105:106 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 1 45 dep Roseoloviruses 49:62 arg1 Roseoloviruses 49:62 Roseoloviruses 49:62 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) 49:107 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 1 45 dep Roseoloviruses 49:62 arg1 [HHV-6A 86:92 human herpesvirus 6A [HHV-6A] 65:93 human herpesvirus 6A [HHV-6A] 65:93 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 1 45 dep Roseoloviruses 49:62 arg1 -6B 96:98 -6B 96:98 -6B 96:98 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 0 46 theme Immunoevasin 35:46 arg1 Characterization 0:15 Characterization 0:15 Characterization of the HHV-6B U20 Immunoevasin. 0:47 Characterization of the HHV-6B U20 Immunoevasin. 36688652 1 47 theme host 242:245 arg1 life 230:233 the life 226:233 the life of the host 226:245 Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. 36688652 4 48 theme indicative 834:843 arg1 modifications 795:807 several posttranslational modifications 769:807 several posttranslational modifications 769:807 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 4 49 theme HHV-6B 700:705 arg1 U20 707:709 HHV-6B U20 700:709 HHV-6B U20 700:709 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 0 50 theme U20 31:33 arg1 Immunoevasin 35:46 the HHV-6B U20 Immunoevasin 20:46 the HHV-6B U20 Immunoevasin 20:46 Characterization of the HHV-6B U20 Immunoevasin. 36688652 4 51 theme cell 909:912 arg1 surface 914:920 the cell surface 905:920 the cell surface 905:920 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 8 52 theme 92 1349:1350 arg1 % 1351:1351 % 1351:1351 % 1351:1351 Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. 36688652 3 53 dep expression 537:546 arg1 the 533:535 the 533:535 the 533:535 Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. 36688652 7 54 theme virus-encoded 1171:1183 arg1 IMPORTANCE 1126:1135 IMPORTANCE 1126:1135 IMPORTANCE The roseolovirus U20 proteins 1126:1165 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 54 theme virus-encoded 1171:1183 arg1 glycoproteins 1203:1215 virus-encoded integral membrane glycoproteins 1171:1215 virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds 1171:1284 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 3 55 theme genes 664:668 arg1 block 655:659 a block 653:659 a block of genes unique to the roseoloviruses 653:697 Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. 36688652 6 56 theme U20 1096:1098 arg1 s 1090:1090 s 1090:1090 s 1090:1090 These results provide a framework to understand the role(s) of U20 in evading host defenses. 36688652 6 56 theme U20 1096:1098 arg1 role 1085:1088 the role 1081:1088 the role(s) of U20 in evading host defenses 1081:1123 These results provide a framework to understand the role(s) of U20 in evading host defenses. 36688652 7 57 theme U20 1154:1156 arg1 proteins 1158:1165 The roseolovirus U20 proteins 1137:1165 IMPORTANCE The roseolovirus U20 proteins 1126:1165 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 8 58 theme different 1386:1394 arg1 functions 1396:1404 different functions 1386:1404 different functions 1386:1404 Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. 36688652 4 59 theme posttranslational 777:793 arg1 modifications 795:807 several posttranslational modifications 769:807 several posttranslational modifications 769:807 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 7 60 contain possessing 1217:1226 arg1 IMPORTANCE 1126:1135 IMPORTANCE 1126:1135 IMPORTANCE The roseolovirus U20 proteins 1126:1165 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 60 contain possessing 1217:1226 arg2 MHC 1270:1272 MHC 1270:1272 MHC 1270:1272 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 60 contain possessing 1217:1226 arg1 glycoproteins 1203:1215 virus-encoded integral membrane glycoproteins 1171:1215 virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds 1171:1284 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 60 contain possessing 1217:1226 arg2 complex 1261:1267 class I major histocompatibility complex 1228:1267 class I major histocompatibility complex (MHC) 1228:1273 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 8 61 theme % 1351:1351 arg1 identity 1353:1360 92% identity 1349:1360 92% identity 1349:1360 Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. 36688652 10 62 theme trafficking 1970:1980 arg1 glycosylation 1983:1995 glycosylation 1983:1995 glycosylation 1983:1995 Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and posttranslational modifications occurring on HHV6B U20. 36688652 10 62 theme trafficking 1970:1980 arg1 characterization 1946:1961 cell biological and biochemical characterization 1914:1961 cell biological and biochemical characterization of the trafficking 1914:1980 Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and posttranslational modifications occurring on HHV6B U20. 36688652 10 62 theme trafficking 1970:1980 arg1 modifications 2020:2032 posttranslational modifications 2002:2032 posttranslational modifications occurring on HHV6B U20 2002:2055 Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and posttranslational modifications occurring on HHV6B U20. 36688652 9 63 dep Front 1815:1819 arg1 Immunol 1821:1827 Immunol 1821:1827 Immunol 1821:1827 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 3 64 theme posttranslational 566:582 arg1 modifications 584:596 posttranslational modifications 566:596 posttranslational modifications 566:596 Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. 36688652 9 65 theme nonproductive 1583:1595 arg1 infection 1597:1605 nonproductive infection 1583:1605 nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799) 1583:1887 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 9 66 theme NKG2D 1470:1474 arg1 ligands 1476:1482 NKG2D ligands 1470:1482 NKG2D ligands 1470:1482 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 9 67 theme HHV6A 1434:1438 arg1 U20 1440:1442 HHV6A U20 1434:1442 HHV6A U20 1434:1442 HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). 36688652 8 68 theme recent 1363:1368 arg1 studies 1370:1376 recent studies 1363:1376 recent studies 1363:1376 Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. 36688652 8 69 theme U20 1310:1312 arg1 proteins 1314:1321 U20 proteins 1310:1321 U20 proteins from HHV-6A and -6B 1310:1341 Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. 36688652 7 70 theme roseolovirus 1141:1152 arg1 proteins 1158:1165 The roseolovirus U20 proteins 1137:1165 IMPORTANCE The roseolovirus U20 proteins 1126:1165 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 71 theme major 1236:1240 arg1 complex 1261:1267 class I major histocompatibility complex 1228:1267 class I major histocompatibility complex (MHC) 1228:1273 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 71 theme major 1236:1240 arg1 MHC 1270:1272 MHC 1270:1272 MHC 1270:1272 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 4 72 dep trafficked 711:720 arg1 reaching 896:903 reaching 896:903 reaching the cell surface before being internalized 896:946 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 4 72 dep trafficked 711:720 arg1 receiving 759:767 receiving 759:767 receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins 759:878 HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. 36688652 7 73 theme integral 1185:1192 arg1 IMPORTANCE 1126:1135 IMPORTANCE 1126:1135 IMPORTANCE The roseolovirus U20 proteins 1126:1165 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 73 theme integral 1185:1192 arg1 glycoproteins 1203:1215 virus-encoded integral membrane glycoproteins 1171:1215 virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds 1171:1284 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 3 74 theme unique 670:675 arg1 genes 664:668 genes 664:668 genes unique to the roseoloviruses 664:697 Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. 36688652 2 75 theme host 413:416 arg1 life 401:404 the life 397:404 the life of the host 397:416 As such, these viruses are among the most pervasive and stealthy of all viruses; they must necessarily excel at escaping immune detection throughout the life of the host, and yet, very little is known about how these viruses so successfully escape host defenses. 36688652 7 76 theme histocompatibility 1242:1259 arg1 complex 1261:1267 class I major histocompatibility complex 1228:1267 class I major histocompatibility complex (MHC) 1228:1273 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 7 76 theme histocompatibility 1242:1259 arg1 MHC 1270:1272 MHC 1270:1272 MHC 1270:1272 IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. 36688652 10 77 gly glycosylation 1983:1995 arg1 trafficking 1970:1980 the trafficking 1966:1980 the trafficking 1966:1980 Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and posttranslational modifications occurring on HHV6B U20. 36271727 7 0 theme signal 1453:1458 arg1 sequences 1460:1468 honeybee signal sequences 1444:1468 honeybee signal sequences 1444:1468 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 4 1 theme increased 794:802 arg1 secretion 818:826 increased extracellular secretion 794:826 increased extracellular secretion 794:826 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 6 2 link N-linked 1225:1232 arg1 residues 1247:1254 these N-linked carbohydrate residues 1219:1254 these N-linked carbohydrate residues 1219:1254 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 4 3 theme nonstructural 512:524 arg1 NS2B 526:529 viral nonstructural NS2B 506:529 viral nonstructural NS2B 506:529 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 6 4 gly glycoprotein 1122:1133 arg1 glycoprotein 1122:1133 the E glycoprotein 1116:1133 the E glycoprotein 1116:1133 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 2 5 theme unprecedented 132:144 arg1 spread 155:160 an unprecedented pandemic spread 129:160 an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment 129:230 Zika virus (ZIKV) is one of several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment. 36271727 6 6 theme antibody 1194:1201 arg1 reactions 1203:1211 both polyclonal and monoclonal antibody reactions 1163:1211 both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage 1163:1304 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 7 7 theme tropomyosin 1421:1431 arg1 leader 1433:1438 a lobster tropomyosin leader 1411:1438 a lobster tropomyosin leader 1411:1438 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 6 8 theme glycosylation 1099:1111 arg1 importance 1085:1094 The importance 1081:1094 The importance of glycosylation of the E glycoprotein 1081:1133 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 7 9 theme host-cell 1354:1362 arg1 sequence 1388:1395 the host-cell furin protease cleavage sequence 1350:1395 the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences 1350:1468 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 2 10 theme Zika 81:84 arg1 ZIKV 93:96 ZIKV 93:96 ZIKV 93:96 Zika virus (ZIKV) is one of several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment. 36271727 2 10 theme Zika 81:84 arg1 virus 86:90 Zika virus 81:90 Zika virus (ZIKV) 81:97 Zika virus (ZIKV) is one of several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment. 36271727 7 11 theme multifunctional 1603:1617 arg1 ELISA 1631:1635 ELISA 1631:1635 ELISA 1631:1635 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 11 theme multifunctional 1603:1617 arg1 enhancement 1675:1685 neutralization/antibody-dependent enhancement 1641:1685 neutralization/antibody-dependent enhancement 1641:1685 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 11 theme multifunctional 1603:1617 arg1 assays 1688:1693 multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays 1603:1693 multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays 1603:1693 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 4 12 theme different 570:578 arg1 promoters 580:588 one or two different promoters 559:588 one or two different promoters 559:588 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 5 13 theme prM 1014:1016 arg1 glycoprotein 1018:1029 no uncleaved prM glycoprotein 1001:1029 no uncleaved prM glycoprotein 1001:1029 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 3 14 theme ZIKV-like 304:312 arg1 VLPs 330:333 Zika VLPs 325:333 Zika VLPs 325:333 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 3 14 theme ZIKV-like 304:312 arg1 particles 314:322 recombinant baculovirus-derived ZIKV-like particles 272:322 recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) 272:334 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 6 15 gly glycosylation 1099:1111 arg1 glycoprotein 1122:1133 the E glycoprotein 1116:1133 the E glycoprotein 1116:1133 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 5 16 theme HEK293T 982:988 arg1 cells 991:995 both insect (Sf9) and mammalian (HEK293T) cells 949:995 cells 991:995 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 7 17 theme vaccine 1743:1749 arg1 trials 1751:1756 vaccine trials 1743:1756 vaccine trials 1743:1756 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 3 18 theme recombinant 272:282 arg1 VLPs 330:333 Zika VLPs 325:333 Zika VLPs 325:333 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 3 18 theme recombinant 272:282 arg1 particles 314:322 recombinant baculovirus-derived ZIKV-like particles 272:322 recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) 272:334 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 4 19 theme full-length 411:421 arg1 capsid 428:433 the full-length ZIKV capsid 407:433 the full-length ZIKV capsid (C) 407:437 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 4 19 theme full-length 411:421 arg1 C 436:436 C 436:436 C 436:436 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 7 20 dep assays 1688:1693 arg1 ELISA 1631:1635 ELISA 1631:1635 ELISA 1631:1635 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 20 dep assays 1688:1693 arg1 enhancement 1675:1685 neutralization/antibody-dependent enhancement 1641:1685 neutralization/antibody-dependent enhancement 1641:1685 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 20 dep assays 1688:1693 arg1 assays 1688:1693 multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays 1603:1693 multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays 1603:1693 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 6 21 theme N-linked 1225:1232 arg1 residues 1247:1254 these N-linked carbohydrate residues 1219:1254 these N-linked carbohydrate residues 1219:1254 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 5 22 theme virion 867:872 arg1 morphology 874:883 typical virion morphology 859:883 typical virion morphology 859:883 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 6 23 theme glycoprotein 1122:1133 arg1 glycosylation 1099:1111 glycosylation 1099:1111 glycosylation of the E glycoprotein 1099:1133 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 4 24 theme alternative 599:609 arg1 protease 627:634 an alternative host-cell furin protease 596:634 an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion 596:826 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 6 25 from effects 1152:1158 arg1 reactions 1203:1211 both polyclonal and monoclonal antibody reactions 1163:1211 both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage 1163:1304 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 4 26 theme furin 621:625 arg1 protease 627:634 an alternative host-cell furin protease 596:634 an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion 596:826 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 4 27 dep proteins 477:484 arg1 a 499:499 a 499:499 a 499:499 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 5 28 theme Zika 839:842 arg1 VLPs 844:847 All these Zika VLPs 829:847 All these Zika VLPs 829:847 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 3 29 theme ZIKV-antibody 345:357 arg1 interactions 359:370 ZIKV-antibody interactions 345:370 ZIKV-antibody interactions 345:370 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 4 30 theme prM 690:692 arg1 genes 694:698 the C and prM genes 680:698 genes 694:698 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 4 31 with pre-membrane 440:451 arg1 either 491:496 either 491:496 either 491:496 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 6 32 theme enzymatic 1287:1295 arg1 cleavage 1297:1304 enzymatic cleavage 1287:1304 enzymatic cleavage 1287:1304 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 7 33 theme neutralization/antibody-dependent 1641:1673 arg1 enhancement 1675:1685 neutralization/antibody-dependent enhancement 1641:1685 neutralization/antibody-dependent enhancement 1641:1685 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 33 theme neutralization/antibody-dependent 1641:1673 arg1 assays 1688:1693 multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays 1603:1693 multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays 1603:1693 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 0 34 theme Enhanced 0:7 arg1 Zika 9:12 Enhanced Zika 0:12 Enhanced Zika 0:12 Enhanced Zika virus-like particle development using Baculovirus spp. 36271727 4 35 theme C 684:684 arg1 genes 694:698 the C and prM genes 680:698 genes 694:698 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 7 36 theme protease 1370:1377 arg1 sequence 1388:1395 the host-cell furin protease cleavage sequence 1350:1395 the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences 1350:1468 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 37 theme Zika 1505:1508 arg1 construct 1590:1598 a superior construct 1579:1598 a superior construct 1579:1598 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 37 theme Zika 1505:1508 arg1 titers 1514:1519 higher Zika VLP titers 1498:1519 higher Zika VLP titers 1498:1519 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 37 theme Zika 1505:1508 arg1 concentrations 1533:1546 protein concentrations 1525:1546 protein concentrations 1525:1546 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 5 38 theme electron 901:908 arg1 microscopic analysis 910:929 transmission electron microscopic analysis 888:929 transmission electron microscopic analysis 888:929 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 7 39 theme diagnostic 1619:1628 arg1 ELISA 1631:1635 ELISA 1631:1635 ELISA 1631:1635 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 39 theme diagnostic 1619:1628 arg1 enhancement 1675:1685 neutralization/antibody-dependent enhancement 1641:1685 neutralization/antibody-dependent enhancement 1641:1685 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 39 theme diagnostic 1619:1628 arg1 assays 1688:1693 multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays 1603:1693 multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays 1603:1693 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 2 40 theme pandemic 146:153 arg1 spread 155:160 an unprecedented pandemic spread 129:160 an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment 129:230 Zika virus (ZIKV) is one of several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment. 36271727 4 41 theme signal 755:760 arg1 sequences 762:770 honeybee signal sequences 746:770 honeybee signal sequences with one promoter for increased extracellular secretion 746:826 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 0 42 theme Baculovirus 52:62 arg1 spp 64:66 Baculovirus spp 52:66 Baculovirus spp 52:66 Enhanced Zika virus-like particle development using Baculovirus spp. 36271727 5 43 theme insect 954:959 arg1 Sf9 962:964 both insect (Sf9) and mammalian (HEK293T) cells 949:995 Sf9 962:964 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 5 44 gly glycoprotein 1018:1029 arg1 glycoprotein 1018:1029 no uncleaved prM glycoprotein 1001:1029 no uncleaved prM glycoprotein 1001:1029 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 4 45 theme NS3 535:537 arg1 unit 548:551 NS3 protease unit 535:551 NS3 protease unit 535:551 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 4 46 theme tropomyosin 723:733 arg1 leader 735:740 lobster tropomyosin leader 715:740 lobster tropomyosin leader 715:740 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 7 47 theme honeybee 1444:1451 arg1 sequences 1460:1468 honeybee signal sequences 1444:1468 honeybee signal sequences 1444:1468 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 4 48 theme viral 506:510 arg1 NS2B 526:529 viral nonstructural NS2B 506:529 viral nonstructural NS2B 506:529 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 7 49 theme lobster 1413:1419 arg1 leader 1433:1438 a lobster tropomyosin leader 1411:1438 a lobster tropomyosin leader 1411:1438 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 4 50 theme extracellular 804:816 arg1 secretion 818:826 increased extracellular secretion 794:826 increased extracellular secretion 794:826 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 6 51 theme monoclonal 1183:1192 arg1 reactions 1203:1211 both polyclonal and monoclonal antibody reactions 1163:1211 both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage 1163:1304 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 7 52 theme cleavage 1379:1386 arg1 sequence 1388:1395 the host-cell furin protease cleavage sequence 1350:1395 the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences 1350:1468 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 2 53 theme examples 117:124 arg1 one 102:104 one 102:104 one 102:104 Zika virus (ZIKV) is one of several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment. 36271727 2 53 theme examples 117:124 arg1 examples 117:124 several examples 109:124 several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment 109:230 Zika virus (ZIKV) is one of several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment. 36271727 6 54 theme polyclonal 1168:1177 arg1 reactions 1203:1211 both polyclonal and monoclonal antibody reactions 1163:1211 both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage 1163:1304 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 7 55 theme furin 1364:1368 arg1 sequence 1388:1395 the host-cell furin protease cleavage sequence 1350:1395 the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences 1350:1468 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 4 56 with proteins 477:484 arg1 either 491:496 either 491:496 either 491:496 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 7 57 theme superior 1581:1588 arg1 construct 1590:1598 a superior construct 1579:1598 a superior construct 1579:1598 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 57 theme superior 1581:1588 arg1 titers 1514:1519 higher Zika VLP titers 1498:1519 higher Zika VLP titers 1498:1519 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 57 theme superior 1581:1588 arg1 concentrations 1533:1546 protein concentrations 1525:1546 protein concentrations 1525:1546 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 5 58 theme uncleaved 1004:1012 arg1 glycoprotein 1018:1029 no uncleaved prM glycoprotein 1001:1029 no uncleaved prM glycoprotein 1001:1029 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 2 59 theme suitable 202:209 arg1 vaccine 211:217 no suitable vaccine 199:217 no suitable vaccine 199:217 Zika virus (ZIKV) is one of several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment. 36271727 4 60 theme ZIKV 423:426 arg1 capsid 428:433 the full-length ZIKV capsid 407:433 the full-length ZIKV capsid (C) 407:437 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 4 60 theme ZIKV 423:426 arg1 C 436:436 C 436:436 C 436:436 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 6 61 theme carbohydrate 1234:1245 arg1 residues 1247:1254 these N-linked carbohydrate residues 1219:1254 these N-linked carbohydrate residues 1219:1254 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 5 62 theme typical 859:865 arg1 morphology 874:883 typical virion morphology 859:883 typical virion morphology 859:883 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 3 63 theme baculovirus-derived 284:302 arg1 VLPs 330:333 Zika VLPs 325:333 Zika VLPs 325:333 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 3 63 theme baculovirus-derived 284:302 arg1 particles 314:322 recombinant baculovirus-derived ZIKV-like particles 272:322 recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) 272:334 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 4 64 theme cleavage 645:652 arg1 sequence 654:661 cleavage sequence 645:661 cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion 645:826 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 7 65 theme immunogenic 1699:1709 arg1 assessments 1711:1721 immunogenic assessments 1699:1721 immunogenic assessments 1699:1721 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 4 66 theme envelope 464:471 arg1 proteins 477:484 envelope (E) proteins 464:484 envelope (E) proteins with either: a 464:499 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 6 67 theme E 1120:1120 arg1 glycoprotein 1122:1133 the E glycoprotein 1116:1133 the E glycoprotein 1116:1133 The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N-linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. 36271727 4 68 with leader 735:740 arg1 promoter 781:788 one promoter 777:788 one promoter for increased extracellular secretion 777:826 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 7 69 theme protein 1525:1531 arg1 construct 1590:1598 a superior construct 1579:1598 a superior construct 1579:1598 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 69 theme protein 1525:1531 arg1 titers 1514:1519 higher Zika VLP titers 1498:1519 higher Zika VLP titers 1498:1519 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 69 theme protein 1525:1531 arg1 concentrations 1533:1546 protein concentrations 1525:1546 protein concentrations 1525:1546 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 3 70 theme Zika 325:328 arg1 VLPs 330:333 Zika VLPs 325:333 Zika VLPs 325:333 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 3 70 theme Zika 325:328 arg1 particles 314:322 recombinant baculovirus-derived ZIKV-like particles 272:322 recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) 272:334 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 4 71 theme E 474:474 arg1 proteins 477:484 envelope (E) proteins 464:484 envelope (E) proteins with either: a 464:499 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 4 72 theme host-cell 611:619 arg1 protease 627:634 an alternative host-cell furin protease 596:634 an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion 596:826 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 5 73 theme immature 1063:1070 arg1 virions 1072:1078 immature virions 1063:1078 immature virions 1063:1078 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 4 74 with sequences 762:770 arg1 promoter 781:788 one promoter 777:788 one promoter for increased extracellular secretion 777:826 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 4 75 dep NS2B 526:529 arg1 the 502:504 the 502:504 the 502:504 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 0 76 theme particle 25:32 arg1 development 34:44 particle development 25:44 particle development 25:44 Enhanced Zika virus-like particle development using Baculovirus spp. 36271727 7 77 contain contained 1340:1348 arg2 sequence 1388:1395 the host-cell furin protease cleavage sequence 1350:1395 the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences 1350:1468 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 77 contain contained 1340:1348 arg1 construct 1324:1332 the construct 1320:1332 the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter 1320:1487 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 5 78 theme transmission 888:899 arg1 microscopic analysis 910:929 transmission electron microscopic analysis 888:929 transmission electron microscopic analysis 888:929 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 4 79 with capsid 428:433 arg1 either 491:496 either 491:496 either 491:496 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 7 80 theme VLP 1510:1512 arg1 construct 1590:1598 a superior construct 1579:1598 a superior construct 1579:1598 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 80 theme VLP 1510:1512 arg1 titers 1514:1519 higher Zika VLP titers 1498:1519 higher Zika VLP titers 1498:1519 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 80 theme VLP 1510:1512 arg1 concentrations 1533:1546 protein concentrations 1525:1546 protein concentrations 1525:1546 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 2 81 theme spread 155:160 arg1 examples 117:124 several examples 109:124 several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment 109:230 Zika virus (ZIKV) is one of several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment. 36271727 7 82 theme higher 1498:1503 arg1 construct 1590:1598 a superior construct 1579:1598 a superior construct 1579:1598 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 82 theme higher 1498:1503 arg1 titers 1514:1519 higher Zika VLP titers 1498:1519 higher Zika VLP titers 1498:1519 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 7 82 theme higher 1498:1503 arg1 concentrations 1533:1546 protein concentrations 1525:1546 protein concentrations 1525:1546 Importantly, the construct which contained the host-cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody-dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials. 36271727 5 83 theme mammalian 971:979 arg1 cells 991:995 both insect (Sf9) and mammalian (HEK293T) cells 949:995 cells 991:995 All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. 36271727 4 84 theme honeybee 746:753 arg1 sequences 762:770 honeybee signal sequences 746:770 honeybee signal sequences with one promoter for increased extracellular secretion 746:826 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 3 85 link baculovirus-derived 284:302 arg1 VLPs 330:333 Zika VLPs 325:333 Zika VLPs 325:333 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 3 85 link baculovirus-derived 284:302 arg1 particles 314:322 recombinant baculovirus-derived ZIKV-like particles 272:322 recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) 272:334 Here, we constructed and characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. 36271727 4 86 theme protease 539:546 arg1 unit 548:551 NS3 protease unit 535:551 NS3 protease unit 535:551 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 36271727 2 87 theme several 109:115 arg1 examples 117:124 several examples 109:124 several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment 109:230 Zika virus (ZIKV) is one of several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment. 36271727 4 88 theme lobster 715:721 arg1 leader 735:740 lobster tropomyosin leader 715:740 lobster tropomyosin leader 715:740 These VLPs, uniquely consisted of the full-length ZIKV capsid (C), pre-membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host-cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. 35680340 0 0 theme selective 98:106 arg1 enrichment 108:117 selective enrichment 98:117 selective enrichment of glycopeptides 98:134 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 2 1 theme aldehyde 490:497 arg1 monomers 499:506 two aldehyde monomers 486:506 two aldehyde monomers 486:506 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 2 1 theme aldehyde 490:497 arg1 m-phthalaldehyde 537:552 m-phthalaldehyde 537:552 m-phthalaldehyde (mPAL) 537:559 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 2 1 theme aldehyde 490:497 arg1 p-phthalaldehyde 509:524 p-phthalaldehyde 509:524 p-phthalaldehyde (pPAL) 509:531 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 9 2 theme glycopeptides 1464:1476 arg1 identification 1423:1436 identification 1423:1436 identification 1423:1436 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 9 2 theme glycopeptides 1464:1476 arg1 enrichment 1408:1417 enrichment 1408:1417 enrichment 1408:1417 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 1 3 theme porous 172:177 arg1 POPs 197:200 POPs 197:200 POPs 197:200 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 1 3 theme porous 172:177 arg1 polymers 187:194 nitrogen-rich linear porous organic polymers 151:194 nitrogen-rich linear porous organic polymers (POPs) 151:201 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 9 4 theme POP 1370:1372 arg1 materials 1374:1382 these CH-based hydrophilic POP materials 1343:1382 these CH-based hydrophilic POP materials 1343:1382 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 9 5 theme biological 1495:1504 arg1 samples 1506:1512 complicated biological samples 1483:1512 complicated biological samples 1483:1512 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 9 6 dep enrichment 1408:1417 arg1 the 1404:1406 the 1404:1406 the 1404:1406 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 9 7 theme CH-based 1349:1356 arg1 materials 1374:1382 these CH-based hydrophilic POP materials 1343:1382 these CH-based hydrophilic POP materials 1343:1382 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 1 8 theme organic 179:185 arg1 POPs 197:200 POPs 197:200 POPs 197:200 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 1 8 theme organic 179:185 arg1 polymers 187:194 nitrogen-rich linear porous organic polymers 151:194 nitrogen-rich linear porous organic polymers (POPs) 151:201 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 8 9 attach derived 1133:1139 arg1 170 1146:1148 170 1146:1148 170 1146:1148 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins were identified after the enrichment by CH-pPAL and CH-mPAL within three independent replicates of proteins extracted from human serum, respectively. 35680340 8 9 attach derived 1133:1139 arg1 proteins 1173:1180 200 N-glycosylated proteins 1154:1180 200 N-glycosylated proteins 1154:1180 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins were identified after the enrichment by CH-pPAL and CH-mPAL within three independent replicates of proteins extracted from human serum, respectively. 35680340 8 9 attach derived 1133:1139 arg2 glycopeptides 1119:1131 The 851 and 794 unique glycopeptides 1096:1131 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins 1096:1180 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins were identified after the enrichment by CH-pPAL and CH-mPAL within three independent replicates of proteins extracted from human serum, respectively. 35680340 1 10 gly glycopeptides 228:240 arg2 glycopeptides 228:240 glycopeptides enrichment efficiency 228:262 glycopeptides enrichment efficiency 228:262 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 9 11 theme hydrophilic 1358:1368 arg1 materials 1374:1382 these CH-based hydrophilic POP materials 1343:1382 these CH-based hydrophilic POP materials 1343:1382 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 8 12 dep independent 1255:1265 arg1 replicates 1267:1276 replicates 1267:1276 replicates 1267:1276 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins were identified after the enrichment by CH-pPAL and CH-mPAL within three independent replicates of proteins extracted from human serum, respectively. 35680340 9 13 from identification 1423:1436 arg1 samples 1506:1512 complicated biological samples 1483:1512 complicated biological samples 1483:1512 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 2 14 theme POPs 293:296 arg1 kinds 278:282 Two kinds 274:282 Two kinds of novel POPs (CH-pPAL and CH-mPAL) 274:318 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 4 15 theme narrow 711:716 arg1 peaks 718:722 several narrow peaks 703:722 several narrow peaks 703:722 Based on the hydrogen-bond interaction, several narrow peaks existed in the PXRD patterns. 35680340 4 16 theme hydrogen-bond 676:688 arg1 interaction 690:700 the hydrogen-bond interaction 672:700 the hydrogen-bond interaction 672:700 Based on the hydrogen-bond interaction, several narrow peaks existed in the PXRD patterns. 35680340 2 17 theme novel 287:291 arg1 POPs 293:296 novel POPs 287:296 novel POPs (CH-pPAL and CH-mPAL) 287:318 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 9 18 from samples 1506:1512 arg1 identification 1423:1436 identification 1423:1436 identification 1423:1436 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 9 18 from samples 1506:1512 arg1 enrichment 1408:1417 enrichment 1408:1417 enrichment 1408:1417 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 9 18 from samples 1506:1512 arg1 glycopeptides 1464:1476 low-abundance N-linked glycopeptides 1441:1476 low-abundance N-linked glycopeptides from complicated biological samples 1441:1512 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 0 19 theme glycopeptides 122:134 arg1 enrichment 108:117 selective enrichment 98:117 selective enrichment of glycopeptides 98:134 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 6 20 theme severally 893:901 arg1 35.4° 907:911 35.4° 907:911 35.4° 907:911 The contact angle of CH-pPAL and CH-mPAL severally was 35.4° and 28.8°, respectively, indicating excellent hydrophilicity of as-synthesized POPs. 35680340 6 20 theme severally 893:901 arg1 angle 864:868 The contact angle 852:868 The contact angle of CH-pPAL and CH-mPAL severally 852:901 The contact angle of CH-pPAL and CH-mPAL severally was 35.4° and 28.8°, respectively, indicating excellent hydrophilicity of as-synthesized POPs. 35680340 5 21 theme micron-sized 768:779 arg1 CH-pPAL 791:797 micron-sized spherical CH-pPAL 768:797 micron-sized spherical CH-pPAL 768:797 Particularly, micron-sized spherical CH-pPAL possessed a honeycomb-like orderly tunnel structure. 35680340 5 22 theme honeycomb-like 811:824 arg1 structure 841:849 a honeycomb-like orderly tunnel structure 809:849 a honeycomb-like orderly tunnel structure 809:849 Particularly, micron-sized spherical CH-pPAL possessed a honeycomb-like orderly tunnel structure. 35680340 8 23 gly glycopeptides 1119:1131 arg2 glycopeptides 1119:1131 The 851 and 794 unique glycopeptides 1096:1131 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins 1096:1180 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins were identified after the enrichment by CH-pPAL and CH-mPAL within three independent replicates of proteins extracted from human serum, respectively. 35680340 9 24 theme N-linked 1455:1462 arg1 glycopeptides 1464:1476 low-abundance N-linked glycopeptides 1441:1476 low-abundance N-linked glycopeptides from complicated biological samples 1441:1512 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 6 25 theme CH-mPAL 885:891 arg1 severally 893:901 CH-pPAL and CH-mPAL severally 873:901 CH-pPAL and CH-mPAL severally 873:901 The contact angle of CH-pPAL and CH-mPAL severally was 35.4° and 28.8°, respectively, indicating excellent hydrophilicity of as-synthesized POPs. 35680340 0 26 theme One-step 0:7 arg1 fabrication 9:19 One-step fabrication 0:19 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 0:135 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 9 27 link N-linked 1455:1462 arg1 glycopeptides 1464:1476 low-abundance N-linked glycopeptides 1441:1476 low-abundance N-linked glycopeptides from complicated biological samples 1441:1512 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 6 28 theme contact 856:862 arg1 35.4° 907:911 35.4° 907:911 35.4° 907:911 The contact angle of CH-pPAL and CH-mPAL severally was 35.4° and 28.8°, respectively, indicating excellent hydrophilicity of as-synthesized POPs. 35680340 6 28 theme contact 856:862 arg1 angle 864:868 The contact angle 852:868 The contact angle of CH-pPAL and CH-mPAL severally 852:901 The contact angle of CH-pPAL and CH-mPAL severally was 35.4° and 28.8°, respectively, indicating excellent hydrophilicity of as-synthesized POPs. 35680340 8 29 theme human 1305:1309 arg1 serum 1311:1315 human serum 1305:1315 human serum 1305:1315 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins were identified after the enrichment by CH-pPAL and CH-mPAL within three independent replicates of proteins extracted from human serum, respectively. 35680340 0 30 theme nitrogen-rich 24:36 arg1 sphere 87:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 6 31 theme POPs 992:995 arg1 hydrophilicity 959:972 excellent hydrophilicity 949:972 excellent hydrophilicity of as-synthesized POPs 949:995 The contact angle of CH-pPAL and CH-mPAL severally was 35.4° and 28.8°, respectively, indicating excellent hydrophilicity of as-synthesized POPs. 35680340 8 32 theme unique 1112:1117 arg1 glycopeptides 1119:1131 The 851 and 794 unique glycopeptides 1096:1131 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins 1096:1180 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins were identified after the enrichment by CH-pPAL and CH-mPAL within three independent replicates of proteins extracted from human serum, respectively. 35680340 0 33 gly glycopeptides 122:134 arg2 glycopeptides 122:134 glycopeptides 122:134 glycopeptides 122:134 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 9 34 gly glycopeptides 1464:1476 arg1 samples 1506:1512 complicated biological samples 1483:1512 complicated biological samples 1483:1512 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 9 34 gly glycopeptides 1464:1476 arg2 glycopeptides 1464:1476 low-abundance N-linked glycopeptides 1441:1476 low-abundance N-linked glycopeptides from complicated biological samples 1441:1512 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 5 35 theme tunnel 834:839 arg1 structure 841:849 a honeycomb-like orderly tunnel structure 809:849 a honeycomb-like orderly tunnel structure 809:849 Particularly, micron-sized spherical CH-pPAL possessed a honeycomb-like orderly tunnel structure. 35680340 6 36 theme as-synthesized 977:990 arg1 POPs 992:995 as-synthesized POPs 977:995 as-synthesized POPs 977:995 The contact angle of CH-pPAL and CH-mPAL severally was 35.4° and 28.8°, respectively, indicating excellent hydrophilicity of as-synthesized POPs. 35680340 9 37 from enrichment 1408:1417 arg1 samples 1506:1512 complicated biological samples 1483:1512 complicated biological samples 1483:1512 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 2 38 dep POPs 293:296 arg1 CH-mPAL 311:317 CH-mPAL 311:317 CH-mPAL 311:317 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 2 38 dep POPs 293:296 arg1 CH-pPAL 299:305 CH-pPAL 299:305 CH-pPAL 299:305 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 2 39 theme amine 437:441 arg1 monomer 443:449 a flexible amine monomer 426:449 a flexible amine monomer (carbohydrazide, CH) 426:470 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 0 40 theme porous 45:50 arg1 sphere 87:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 6 41 theme CH-pPAL 873:879 arg1 severally 893:901 CH-pPAL and CH-mPAL severally 873:901 CH-pPAL and CH-mPAL severally 873:901 The contact angle of CH-pPAL and CH-mPAL severally was 35.4° and 28.8°, respectively, indicating excellent hydrophilicity of as-synthesized POPs. 35680340 3 42 theme surface 589:595 arg1 area 597:600 The specific surface area 576:600 The specific surface area of CH-pPAL and CH-mPAL 576:623 The specific surface area of CH-pPAL and CH-mPAL was 238 and 232 m2 g-1, respectively. 35680340 3 42 theme surface 589:595 arg1 238 629:631 238 629:631 238 629:631 The specific surface area of CH-pPAL and CH-mPAL was 238 and 232 m2 g-1, respectively. 35680340 8 43 gly 200 N-glycosylated 1154:1171 arg1 proteins 1173:1180 200 N-glycosylated proteins 1154:1180 200 N-glycosylated proteins 1154:1180 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins were identified after the enrichment by CH-pPAL and CH-mPAL within three independent replicates of proteins extracted from human serum, respectively. 35680340 2 44 theme flexible 428:435 arg1 monomer 443:449 a flexible amine monomer 426:449 a flexible amine monomer (carbohydrazide, CH) 426:470 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 0 45 theme linear 38:43 arg1 sphere 87:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 2 46 theme Schiff-base 351:361 arg1 reaction 376:383 the Schiff-base condensation reaction 347:383 the Schiff-base condensation reaction 347:383 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 5 47 theme spherical 781:789 arg1 CH-pPAL 791:797 micron-sized spherical CH-pPAL 768:797 micron-sized spherical CH-pPAL 768:797 Particularly, micron-sized spherical CH-pPAL possessed a honeycomb-like orderly tunnel structure. 35680340 5 48 theme orderly 826:832 arg1 structure 841:849 a honeycomb-like orderly tunnel structure 809:849 a honeycomb-like orderly tunnel structure 809:849 Particularly, micron-sized spherical CH-pPAL possessed a honeycomb-like orderly tunnel structure. 35680340 7 49 theme high 1042:1045 arg1 capacity 1058:1065 high adsorption capacity 1042:1065 high adsorption capacity 1042:1065 They both demonstrated high sensitivity and high adsorption capacity in glycopeptides enrichment. 35680340 0 50 theme polymer-based 60:72 arg1 sphere 87:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 6 51 theme excellent 949:957 arg1 hydrophilicity 959:972 excellent hydrophilicity 949:972 excellent hydrophilicity of as-synthesized POPs 949:995 The contact angle of CH-pPAL and CH-mPAL severally was 35.4° and 28.8°, respectively, indicating excellent hydrophilicity of as-synthesized POPs. 35680340 7 52 theme glycopeptides 1070:1082 arg1 enrichment 1084:1093 glycopeptides enrichment 1070:1093 glycopeptides enrichment 1070:1093 They both demonstrated high sensitivity and high adsorption capacity in glycopeptides enrichment. 35680340 2 53 dep monomer 443:449 arg1 CH 468:469 CH 468:469 CH 468:469 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 2 53 dep monomer 443:449 arg1 carbohydrazide 452:465 carbohydrazide 452:465 carbohydrazide 452:465 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 7 54 theme adsorption 1047:1056 arg1 capacity 1058:1065 high adsorption capacity 1042:1065 high adsorption capacity 1042:1065 They both demonstrated high sensitivity and high adsorption capacity in glycopeptides enrichment. 35680340 4 55 theme several 703:709 arg1 peaks 718:722 several narrow peaks 703:722 several narrow peaks 703:722 Based on the hydrogen-bond interaction, several narrow peaks existed in the PXRD patterns. 35680340 0 56 theme organic 52:58 arg1 sphere 87:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 5 57 contain possessed 799:807 arg1 CH-pPAL 791:797 micron-sized spherical CH-pPAL 768:797 micron-sized spherical CH-pPAL 768:797 Particularly, micron-sized spherical CH-pPAL possessed a honeycomb-like orderly tunnel structure. 35680340 5 57 contain possessed 799:807 arg2 structure 841:849 a honeycomb-like orderly tunnel structure 809:849 a honeycomb-like orderly tunnel structure 809:849 Particularly, micron-sized spherical CH-pPAL possessed a honeycomb-like orderly tunnel structure. 35680340 3 58 theme specific 580:587 arg1 area 597:600 The specific surface area 576:600 The specific surface area of CH-pPAL and CH-mPAL 576:623 The specific surface area of CH-pPAL and CH-mPAL was 238 and 232 m2 g-1, respectively. 35680340 3 58 theme specific 580:587 arg1 238 629:631 238 629:631 238 629:631 The specific surface area of CH-pPAL and CH-mPAL was 238 and 232 m2 g-1, respectively. 35680340 7 59 gly glycopeptides 1070:1082 arg2 glycopeptides 1070:1082 glycopeptides enrichment 1070:1093 glycopeptides enrichment 1070:1093 They both demonstrated high sensitivity and high adsorption capacity in glycopeptides enrichment. 35680340 9 60 theme low-abundance 1441:1453 arg1 glycopeptides 1464:1476 low-abundance N-linked glycopeptides 1441:1476 low-abundance N-linked glycopeptides from complicated biological samples 1441:1512 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 35680340 8 61 theme 200 N-glycosylated 1154:1171 arg1 proteins 1173:1180 200 N-glycosylated proteins 1154:1180 200 N-glycosylated proteins 1154:1180 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins were identified after the enrichment by CH-pPAL and CH-mPAL within three independent replicates of proteins extracted from human serum, respectively. 35680340 4 62 theme PXRD 739:742 arg1 patterns 744:751 the PXRD patterns 735:751 the PXRD patterns 735:751 Based on the hydrogen-bond interaction, several narrow peaks existed in the PXRD patterns. 35680340 1 63 theme glycopeptides 228:240 arg1 efficiency 253:262 glycopeptides enrichment efficiency 228:262 glycopeptides enrichment efficiency 228:262 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 3 64 theme CH-mPAL 617:623 arg1 area 597:600 The specific surface area 576:600 The specific surface area of CH-pPAL and CH-mPAL 576:623 The specific surface area of CH-pPAL and CH-mPAL was 238 and 232 m2 g-1, respectively. 35680340 3 64 theme CH-mPAL 617:623 arg1 238 629:631 238 629:631 238 629:631 The specific surface area of CH-pPAL and CH-mPAL was 238 and 232 m2 g-1, respectively. 35680340 1 65 theme linear 165:170 arg1 POPs 197:200 POPs 197:200 POPs 197:200 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 1 65 theme linear 165:170 arg1 polymers 187:194 nitrogen-rich linear porous organic polymers 151:194 nitrogen-rich linear porous organic polymers (POPs) 151:201 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 8 66 theme proteins 1281:1288 arg1 independent 1255:1265 independent 1255:1265 independent 1255:1265 The 851 and 794 unique glycopeptides derived from 170 and 200 N-glycosylated proteins were identified after the enrichment by CH-pPAL and CH-mPAL within three independent replicates of proteins extracted from human serum, respectively. 35680340 1 67 theme enrichment 242:251 arg1 efficiency 253:262 glycopeptides enrichment efficiency 228:262 glycopeptides enrichment efficiency 228:262 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 0 68 theme sphere 87:92 arg1 fabrication 9:19 One-step fabrication 0:19 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 0:135 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 7 69 theme high 1021:1024 arg1 sensitivity 1026:1036 high sensitivity 1021:1036 high sensitivity 1021:1036 They both demonstrated high sensitivity and high adsorption capacity in glycopeptides enrichment. 35680340 1 70 theme nitrogen-rich 151:163 arg1 POPs 197:200 POPs 197:200 POPs 197:200 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 1 70 theme nitrogen-rich 151:163 arg1 polymers 187:194 nitrogen-rich linear porous organic polymers 151:194 nitrogen-rich linear porous organic polymers (POPs) 151:201 In this work, nitrogen-rich linear porous organic polymers (POPs) were designed to improve glycopeptides enrichment efficiency in HILIC. 35680340 0 71 theme micron-sized 74:85 arg1 sphere 87:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 nitrogen-rich linear porous organic polymer-based micron-sized sphere 24:92 One-step fabrication of nitrogen-rich linear porous organic polymer-based micron-sized sphere for selective enrichment of glycopeptides. 35680340 3 72 theme CH-pPAL 605:611 arg1 area 597:600 The specific surface area 576:600 The specific surface area of CH-pPAL and CH-mPAL 576:623 The specific surface area of CH-pPAL and CH-mPAL was 238 and 232 m2 g-1, respectively. 35680340 3 72 theme CH-pPAL 605:611 arg1 238 629:631 238 629:631 238 629:631 The specific surface area of CH-pPAL and CH-mPAL was 238 and 232 m2 g-1, respectively. 35680340 2 73 theme condensation 363:374 arg1 reaction 376:383 the Schiff-base condensation reaction 347:383 the Schiff-base condensation reaction 347:383 Two kinds of novel POPs (CH-pPAL and CH-mPAL) were one-step prepared via the Schiff-base condensation reaction and intermolecular hydrogen-bonded using a flexible amine monomer (carbohydrazide, CH) to react with two aldehyde monomers, p-phthalaldehyde (pPAL) and m-phthalaldehyde (mPAL), respectively. 35680340 9 74 theme complicated 1483:1493 arg1 samples 1506:1512 complicated biological samples 1483:1512 complicated biological samples 1483:1512 Therefore, these CH-based hydrophilic POP materials would be applied in the enrichment and identification of low-abundance N-linked glycopeptides from complicated biological samples. 36301074 6 0 from concentrations 931:944 arg1 inhibitory 912:921 inhibitory 912:921 inhibitory 912:921 This mechanism is confirmed by our electrophysiology experiments, which show that D-serine is indeed inhibitory at high concentrations. 36301074 6 1 theme high 926:929 arg1 concentrations 931:944 high concentrations 926:944 high concentrations 926:944 This mechanism is confirmed by our electrophysiology experiments, which show that D-serine is indeed inhibitory at high concentrations. 36301074 1 2 theme agonists 164:171 arg1 binding 122:128 binding 122:128 binding of two different neurotransmitter agonists for synaptic transmission 122:197 N-methyl-D-aspartate receptors (NMDARs) uniquely require binding of two different neurotransmitter agonists for synaptic transmission. 36301074 5 3 dep GluN1 716:720 arg1 LBDs 733:736 LBDs 733:736 LBDs 733:736 Surprisingly, we observed D-serine binding to both GluN1 and GluN2A LBDs, suggesting that D-serine competes with glutamate for binding to GluN2A. 36301074 9 4 theme conformation-dependent 1314:1335 arg1 pathways 1337:1344 These conformation-dependent pathways 1308:1344 These conformation-dependent pathways 1308:1344 These conformation-dependent pathways were not significantly impacted by the presence of N-linked glycans, which act primarily by interacting with the LBD bottom lobe to stabilize the closed LBD. 36301074 7 5 theme sufficient 1141:1150 arg1 force 1152:1156 sufficient force 1141:1156 sufficient force for ion channel gating 1141:1179 Although free energy calculations indicate that D-serine stabilizes the closed GluN2A LBD, its inhibitory behavior suggests that it either does not remain bound long enough or does not generate sufficient force for ion channel gating. 36301074 3 6 theme ligand-binding 339:352 arg1 LBDs 363:366 LBDs 363:366 LBDs 363:366 These agonists bind to the receptor's bi-lobed ligand-binding domains (LBDs), which close around the agonist during receptor activation. 36301074 3 6 theme ligand-binding 339:352 arg1 domains 354:360 the receptor's bi-lobed ligand-binding domains 315:360 the receptor's bi-lobed ligand-binding domains (LBDs) 315:367 These agonists bind to the receptor's bi-lobed ligand-binding domains (LBDs), which close around the agonist during receptor activation. 36301074 4 7 theme GluN1/GluN2A 599:610 arg1 dimer 616:620 the GluN1/GluN2A LBD dimer 595:620 the GluN1/GluN2A LBD dimer 595:620 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 4 8 theme unexplored 454:463 arg1 mechanisms 465:474 the unexplored mechanisms 450:474 the unexplored mechanisms by which D-serine contributes to receptor activation 450:527 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 9 9 theme bottom 1463:1468 arg1 lobe 1470:1473 the LBD bottom lobe 1455:1473 the LBD bottom lobe 1455:1473 These conformation-dependent pathways were not significantly impacted by the presence of N-linked glycans, which act primarily by interacting with the LBD bottom lobe to stabilize the closed LBD. 36301074 1 10 theme N-methyl-D-aspartate 65:84 arg1 NMDARs 97:102 NMDARs 97:102 NMDARs 97:102 N-methyl-D-aspartate receptors (NMDARs) uniquely require binding of two different neurotransmitter agonists for synaptic transmission. 36301074 1 10 theme N-methyl-D-aspartate 65:84 arg1 receptors 86:94 N-methyl-D-aspartate receptors 65:94 N-methyl-D-aspartate receptors (NMDARs) 65:103 N-methyl-D-aspartate receptors (NMDARs) uniquely require binding of two different neurotransmitter agonists for synaptic transmission. 36301074 1 11 theme synaptic 177:184 arg1 transmission 186:197 synaptic transmission 177:197 synaptic transmission 177:197 N-methyl-D-aspartate receptors (NMDARs) uniquely require binding of two different neurotransmitter agonists for synaptic transmission. 36301074 3 12 theme bi-lobed 330:337 arg1 LBDs 363:366 LBDs 363:366 LBDs 363:366 These agonists bind to the receptor's bi-lobed ligand-binding domains (LBDs), which close around the agonist during receptor activation. 36301074 3 12 theme bi-lobed 330:337 arg1 domains 354:360 the receptor's bi-lobed ligand-binding domains 315:360 the receptor's bi-lobed ligand-binding domains (LBDs) 315:367 These agonists bind to the receptor's bi-lobed ligand-binding domains (LBDs), which close around the agonist during receptor activation. 36301074 7 13 theme free 956:959 arg1 calculations 968:979 free energy calculations 956:979 free energy calculations 956:979 Although free energy calculations indicate that D-serine stabilizes the closed GluN2A LBD, its inhibitory behavior suggests that it either does not remain bound long enough or does not generate sufficient force for ion channel gating. 36301074 7 14 theme energy 961:966 arg1 calculations 968:979 free energy calculations 956:979 free energy calculations 956:979 Although free energy calculations indicate that D-serine stabilizes the closed GluN2A LBD, its inhibitory behavior suggests that it either does not remain bound long enough or does not generate sufficient force for ion channel gating. 36301074 4 15 theme multi-microsecond 543:559 arg1 simulations 580:590 multi-microsecond molecular dynamics simulations 543:590 multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists 543:662 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 8 16 dep residues 1262:1269 arg1 working 1271:1277 working 1271:1277 working 1271:1277 We developed a workflow using pathway similarity analysis to identify groups of residues working together to promote binding. 36301074 8 17 theme residues 1262:1269 arg1 residues 1262:1269 residues working 1262:1277 residues working 1262:1277 We developed a workflow using pathway similarity analysis to identify groups of residues working together to promote binding. 36301074 8 17 theme residues 1262:1269 arg1 groups 1252:1257 groups 1252:1257 groups of residues working 1252:1277 We developed a workflow using pathway similarity analysis to identify groups of residues working together to promote binding. 36301074 8 18 theme pathway 1212:1218 arg1 analysis 1231:1238 pathway similarity analysis 1212:1238 pathway similarity analysis 1212:1238 We developed a workflow using pathway similarity analysis to identify groups of residues working together to promote binding. 36301074 9 19 theme closed 1492:1497 arg1 LBD 1499:1501 the closed LBD 1488:1501 the closed LBD 1488:1501 These conformation-dependent pathways were not significantly impacted by the presence of N-linked glycans, which act primarily by interacting with the LBD bottom lobe to stabilize the closed LBD. 36301074 0 20 theme inhibitory 15:24 arg1 D-serine 26:33 inhibitory D-serine 15:33 inhibitory D-serine 15:33 Excitatory and inhibitory D-serine binding to the NMDA receptor. 36301074 4 21 theme dynamics 571:578 arg1 simulations 580:590 multi-microsecond molecular dynamics simulations 543:590 multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists 543:662 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 7 22 theme ion 1162:1164 arg1 gating 1174:1179 ion channel gating 1162:1179 ion channel gating 1162:1179 Although free energy calculations indicate that D-serine stabilizes the closed GluN2A LBD, its inhibitory behavior suggests that it either does not remain bound long enough or does not generate sufficient force for ion channel gating. 36301074 4 23 theme molecular 561:569 arg1 simulations 580:590 multi-microsecond molecular dynamics simulations 543:590 multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists 543:662 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 3 24 theme receptor 408:415 arg1 activation 417:426 receptor activation 408:426 receptor activation 408:426 These agonists bind to the receptor's bi-lobed ligand-binding domains (LBDs), which close around the agonist during receptor activation. 36301074 9 25 theme N-linked 1397:1404 arg1 glycans 1406:1412 N-linked glycans 1397:1412 N-linked glycans 1397:1412 These conformation-dependent pathways were not significantly impacted by the presence of N-linked glycans, which act primarily by interacting with the LBD bottom lobe to stabilize the closed LBD. 36301074 7 26 theme channel 1166:1172 arg1 gating 1174:1179 ion channel gating 1162:1179 ion channel gating 1162:1179 Although free energy calculations indicate that D-serine stabilizes the closed GluN2A LBD, its inhibitory behavior suggests that it either does not remain bound long enough or does not generate sufficient force for ion channel gating. 36301074 4 27 theme glutamate 645:653 arg1 agonists 655:662 glutamate agonists 645:662 glutamate agonists 645:662 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 0 28 theme NMDA 50:53 arg1 receptor 55:62 the NMDA receptor 46:62 the NMDA receptor 46:62 Excitatory and inhibitory D-serine binding to the NMDA receptor. 36301074 4 29 theme receptor 509:516 arg1 activation 518:527 receptor activation 509:527 receptor activation 509:527 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 8 30 theme similarity 1220:1229 arg1 analysis 1231:1238 pathway similarity analysis 1212:1238 pathway similarity analysis 1212:1238 We developed a workflow using pathway similarity analysis to identify groups of residues working together to promote binding. 36301074 7 31 theme inhibitory 1042:1051 arg1 behavior 1053:1060 its inhibitory behavior 1038:1060 its inhibitory behavior 1038:1060 Although free energy calculations indicate that D-serine stabilizes the closed GluN2A LBD, its inhibitory behavior suggests that it either does not remain bound long enough or does not generate sufficient force for ion channel gating. 36301074 5 32 theme D-serine 691:698 arg1 binding 700:706 D-serine binding 691:706 D-serine binding to both GluN1 and GluN2A LBDs 691:736 Surprisingly, we observed D-serine binding to both GluN1 and GluN2A LBDs, suggesting that D-serine competes with glutamate for binding to GluN2A. 36301074 6 33 theme electrophysiology 846:862 arg1 experiments 864:874 our electrophysiology experiments 842:874 our electrophysiology experiments 842:874 This mechanism is confirmed by our electrophysiology experiments, which show that D-serine is indeed inhibitory at high concentrations. 36301074 9 34 link N-linked 1397:1404 arg1 glycans 1406:1412 N-linked glycans 1397:1412 N-linked glycans 1397:1412 These conformation-dependent pathways were not significantly impacted by the presence of N-linked glycans, which act primarily by interacting with the LBD bottom lobe to stabilize the closed LBD. 36301074 4 35 theme dimer 616:620 arg1 simulations 580:590 multi-microsecond molecular dynamics simulations 543:590 multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists 543:662 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 7 36 theme closed 1019:1024 arg1 LBD 1033:1035 the closed GluN2A LBD 1015:1035 the closed GluN2A LBD 1015:1035 Although free energy calculations indicate that D-serine stabilizes the closed GluN2A LBD, its inhibitory behavior suggests that it either does not remain bound long enough or does not generate sufficient force for ion channel gating. 36301074 4 37 theme LBD 612:614 arg1 dimer 616:620 the GluN1/GluN2A LBD dimer 595:620 the GluN1/GluN2A LBD dimer 595:620 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 7 38 theme GluN2A 1026:1031 arg1 LBD 1033:1035 the closed GluN2A LBD 1015:1035 the closed GluN2A LBD 1015:1035 Although free energy calculations indicate that D-serine stabilizes the closed GluN2A LBD, its inhibitory behavior suggests that it either does not remain bound long enough or does not generate sufficient force for ion channel gating. 36301074 1 39 theme different 137:145 arg1 agonists 164:171 two different neurotransmitter agonists 133:171 two different neurotransmitter agonists for synaptic transmission 133:197 N-methyl-D-aspartate receptors (NMDARs) uniquely require binding of two different neurotransmitter agonists for synaptic transmission. 36301074 4 40 theme free 627:630 arg1 D-serine 632:639 free D-serine 627:639 free D-serine 627:639 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 9 41 theme LBD 1459:1461 arg1 lobe 1470:1473 the LBD bottom lobe 1455:1473 the LBD bottom lobe 1455:1473 These conformation-dependent pathways were not significantly impacted by the presence of N-linked glycans, which act primarily by interacting with the LBD bottom lobe to stabilize the closed LBD. 36301074 4 42 with simulations 580:590 arg1 D-serine 632:639 free D-serine 627:639 free D-serine 627:639 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 4 42 with simulations 580:590 arg1 agonists 655:662 glutamate agonists 645:662 glutamate agonists 645:662 To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. 36301074 1 43 theme neurotransmitter 147:162 arg1 agonists 164:171 two different neurotransmitter agonists 133:171 two different neurotransmitter agonists for synaptic transmission 133:197 N-methyl-D-aspartate receptors (NMDARs) uniquely require binding of two different neurotransmitter agonists for synaptic transmission. 36301074 9 44 theme glycans 1406:1412 arg1 presence 1385:1392 the presence 1381:1392 the presence of N-linked glycans, which act primarily by interacting with the LBD bottom lobe to stabilize the closed LBD 1381:1501 These conformation-dependent pathways were not significantly impacted by the presence of N-linked glycans, which act primarily by interacting with the LBD bottom lobe to stabilize the closed LBD. 36041310 9 0 theme circulating 1570:1580 arg1 strains 1588:1594 the circulating field strains 1566:1594 the circulating field strains of SRMV 1566:1602 The findings of the present study revealed changes in fusion protein of some of the circulating field strains of SRMV in Haryana, India. 36041310 2 1 theme Haryana 332:338 arg1 districts 319:327 four districts 314:327 four districts of Haryana, India, 314:346 In this study, 14 PPR suspected outbreaks among sheep and goats were investigated in four districts of Haryana, India, during July 2020 to October, 2021. 36041310 10 2 theme used 1779:1782 arg1 vaccine 1784:1790 currently used vaccine 1769:1790 currently used vaccine 1769:1790 Further detailed studies are warranted to delineate the molecular details of these circulating field strains and to evaluate the effectiveness of currently used vaccine against these mutated strains. 36041310 7 3 theme representative 1081:1094 arg1 samples 1096:1102 representative samples 1081:1102 representative samples 1081:1102 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 3 4 theme full 522:525 arg1 sequences 532:540 full gene sequences 522:540 full gene sequences of fusion protein gene 522:563 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 9 5 theme SRMV 1599:1602 arg1 strains 1588:1594 the circulating field strains 1566:1594 the circulating field strains of SRMV 1566:1602 The findings of the present study revealed changes in fusion protein of some of the circulating field strains of SRMV in Haryana, India. 36041310 2 6 theme suspected 251:259 arg1 outbreaks 261:269 14 PPR suspected outbreaks 244:269 14 PPR suspected outbreaks among sheep and goats 244:291 In this study, 14 PPR suspected outbreaks among sheep and goats were investigated in four districts of Haryana, India, during July 2020 to October, 2021. 36041310 3 7 theme fusion 545:550 arg1 gene 560:563 fusion protein gene 545:563 fusion protein gene 545:563 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 1 8 theme viral 195:199 arg1 disease 201:207 notifiable viral disease 184:207 notifiable viral disease 184:207 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 5 9 dep difference 742:751 arg1 % 847:847 7.55% 843:847 significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55% 730:847 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 5 9 dep difference 742:751 arg1 % 818:818 21% 816:818 significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55% 730:847 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 10 10 theme strains 1724:1730 arg1 details 1689:1695 the molecular details 1675:1695 the molecular details of these circulating field strains 1675:1730 Further detailed studies are warranted to delineate the molecular details of these circulating field strains and to evaluate the effectiveness of currently used vaccine against these mutated strains. 36041310 3 11 theme Reverse 464:470 arg1 Reaction 503:510 Reverse Transcription Polymerase Chain Reaction 464:510 Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene 464:563 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 4 12 from morbidity 606:614 arg1 outbreaks 650:658 these outbreaks 644:658 these outbreaks 644:658 The overall morbidity and cumulative mortality in these outbreaks were 37.56% and 12.09%, respectively. 36041310 8 13 theme reference 1371:1379 arg1 strain 1389:1394 reference vaccine strain 1371:1394 reference vaccine strain 1371:1394 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 4 14 theme cumulative 620:629 arg1 mortality 631:639 cumulative mortality 620:639 cumulative mortality 620:639 The overall morbidity and cumulative mortality in these outbreaks were 37.56% and 12.09%, respectively. 36041310 5 15 from difference 742:751 arg1 mortality 756:764 mortality 756:764 mortality 756:764 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 3 16 theme gene 560:563 arg1 sequences 532:540 full gene sequences 522:540 full gene sequences of fusion protein gene 522:563 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 1 17 theme des 115:117 arg1 petitis 119:125 Peste des petitis ruminants 109:135 Peste des petitis ruminants 109:135 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 1 17 theme des 115:117 arg1 transboundary 166:178 an economically important transboundary 140:178 an economically important transboundary 140:178 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 6 18 theme vaccination 866:876 arg1 status 878:883 the vaccination status 862:883 the vaccination status 862:883 Analysis of the vaccination status revealed significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals as compared to vaccinated ones. 36041310 8 19 theme other 1400:1404 arg1 strains 1417:1423 other lineage IV strains 1400:1423 other lineage IV strains 1400:1423 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 20 gly glycosylation 1448:1460 arg2 three 1479:1483 three 1479:1483 three 1479:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 20 gly glycosylation 1448:1460 arg2 sites 1462:1466 four N-linked glycosylation sites 1434:1466 four N-linked glycosylation sites instead of three 1434:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 20 gly glycosylation 1448:1460 arg2 four 1434:1437 four 1434:1437 four 1434:1437 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 20 gly glycosylation 1448:1460 arg1 three 1479:1483 three 1479:1483 three 1479:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 21 theme IV 1414:1415 arg1 strains 1417:1423 other lineage IV strains 1400:1423 other lineage IV strains 1400:1423 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 5 22 theme significant 730:740 arg1 difference 742:751 significant difference 730:751 significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55% 730:847 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 7 23 theme present 1137:1143 arg1 study 1145:1149 the present study 1133:1149 the present study 1133:1149 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 0 24 theme morbillivirus 76:88 arg1 Epidemiology 0:11 Epidemiology 0:11 Epidemiology 0:11 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 0 24 theme morbillivirus 76:88 arg1 factors 19:25 risk factors 14:25 risk factors 14:25 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 0 24 theme morbillivirus 76:88 arg1 characterization 41:56 molecular characterization 31:56 molecular characterization 31:56 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 1 25 theme important 156:164 arg1 petitis 119:125 Peste des petitis ruminants 109:135 Peste des petitis ruminants 109:135 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 1 25 theme important 156:164 arg1 transboundary 166:178 an economically important transboundary 140:178 an economically important transboundary 140:178 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 8 26 theme N-linked 1439:1446 arg1 sites 1462:1466 four N-linked glycosylation sites 1434:1466 four N-linked glycosylation sites instead of three 1434:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 26 theme N-linked 1439:1446 arg1 three 1479:1483 three 1479:1483 three 1479:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 1 27 dep petitis 119:125 arg1 ruminants 127:135 ruminants 127:135 Peste des petitis ruminants 109:135 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 5 28 theme Risk 698:701 arg1 analysis 710:717 Risk factor analysis 698:717 Risk factor analysis 698:717 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 5 29 from mortality 791:799 arg1 ones 810:813 young ones 804:813 young ones 804:813 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 6 30 with difference 906:915 arg1 higher 949:954 higher 949:954 higher 949:954 Analysis of the vaccination status revealed significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals as compared to vaccinated ones. 36041310 0 31 from characterization 41:56 arg1 India 102:106 India 102:106 India 102:106 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 0 31 from characterization 41:56 arg1 Haryana 93:99 Haryana 93:99 Haryana 93:99 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 7 32 theme lineage 1159:1165 arg1 IV 1167:1168 lineage IV 1159:1168 lineage IV (96.6-99.1%) 1159:1181 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 7 32 theme lineage 1159:1165 arg1 % 1180:1180 96.6-99.1% 1171:1180 96.6-99.1% 1171:1180 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 5 33 theme higher 784:789 arg1 mortality 791:799 higher mortality 784:799 higher mortality in young ones 784:813 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 9 34 theme present 1506:1512 arg1 study 1514:1518 the present study 1502:1518 the present study 1502:1518 The findings of the present study revealed changes in fusion protein of some of the circulating field strains of SRMV in Haryana, India. 36041310 6 35 theme vaccinated 1020:1029 arg1 ones 1031:1034 vaccinated ones 1020:1034 vaccinated ones 1020:1034 Analysis of the vaccination status revealed significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals as compared to vaccinated ones. 36041310 8 36 theme analysis 1310:1317 arg1 comparison 1263:1272 The comparison 1259:1272 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains 1259:1423 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 0 37 theme risk 14:17 arg1 factors 19:25 risk factors 14:25 risk factors 14:25 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 9 38 from changes 1529:1535 arg1 India 1616:1620 India 1616:1620 India 1616:1620 The findings of the present study revealed changes in fusion protein of some of the circulating field strains of SRMV in Haryana, India. 36041310 9 38 from changes 1529:1535 arg1 protein 1547:1553 fusion protein 1540:1553 fusion protein of some of the circulating field strains of SRMV 1540:1602 The findings of the present study revealed changes in fusion protein of some of the circulating field strains of SRMV in Haryana, India. 36041310 8 39 theme fusion 1322:1327 arg1 protein 1329:1335 fusion protein 1322:1335 fusion protein of circulating field strains 1322:1364 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 0 40 theme small 61:65 arg1 morbillivirus 76:88 small ruminant morbillivirus 61:88 small ruminant morbillivirus 61:88 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 5 41 dep % 818:818 arg1 compared 823:830 compared 823:830 compared to adults 823:840 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 10 42 theme detailed 1631:1638 arg1 studies 1640:1646 Further detailed studies 1623:1646 Further detailed studies 1623:1646 Further detailed studies are warranted to delineate the molecular details of these circulating field strains and to evaluate the effectiveness of currently used vaccine against these mutated strains. 36041310 6 43 dep higher 949:954 arg1 mortality 970:978 mortality 970:978 mortality 970:978 Analysis of the vaccination status revealed significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals as compared to vaccinated ones. 36041310 6 43 dep higher 949:954 arg1 morbidity 956:964 morbidity 956:964 morbidity 956:964 Analysis of the vaccination status revealed significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals as compared to vaccinated ones. 36041310 7 44 theme separate 1227:1234 arg1 sub-lineage 1245:1255 sub-lineage 1245:1255 sub-lineage 1245:1255 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 7 44 theme separate 1227:1234 arg1 cluster 1236:1242 a separate cluster 1225:1242 a separate cluster (sub-lineage) 1225:1256 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 8 45 with comparison 1263:1272 arg1 strain 1389:1394 reference vaccine strain 1371:1394 reference vaccine strain 1371:1394 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 45 with comparison 1263:1272 arg1 strains 1417:1423 other lineage IV strains 1400:1423 other lineage IV strains 1400:1423 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 46 theme field 1352:1356 arg1 strains 1358:1364 circulating field strains 1340:1364 circulating field strains 1340:1364 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 3 47 theme ruminant 425:432 arg1 morbillivirus 434:446 small ruminant morbillivirus 419:446 The causative agent of the disease; small ruminant morbillivirus 383:446 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 1 48 theme goats 222:226 arg1 petitis 119:125 Peste des petitis ruminants 109:135 Peste des petitis ruminants 109:135 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 1 48 theme goats 222:226 arg1 transboundary 166:178 an economically important transboundary 140:178 an economically important transboundary 140:178 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 1 48 theme goats 222:226 arg1 disease 201:207 notifiable viral disease 184:207 notifiable viral disease 184:207 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 9 49 theme some 1558:1561 arg1 protein 1547:1553 fusion protein 1540:1553 fusion protein of some of the circulating field strains of SRMV 1540:1602 The findings of the present study revealed changes in fusion protein of some of the circulating field strains of SRMV in Haryana, India. 36041310 10 50 theme mutated 1806:1812 arg1 strains 1814:1820 these mutated strains 1800:1820 these mutated strains 1800:1820 Further detailed studies are warranted to delineate the molecular details of these circulating field strains and to evaluate the effectiveness of currently used vaccine against these mutated strains. 36041310 3 51 theme Transcription 472:484 arg1 Reaction 503:510 Reverse Transcription Polymerase Chain Reaction 464:510 Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene 464:563 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 7 52 theme samples 1096:1102 arg1 sequencing 1041:1050 sequencing 1041:1050 sequencing 1041:1050 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 7 52 theme samples 1096:1102 arg1 analysis 1069:1076 phylogenetic analysis 1056:1076 phylogenetic analysis 1056:1076 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 9 53 theme field 1582:1586 arg1 strains 1588:1594 the circulating field strains 1566:1594 the circulating field strains of SRMV 1566:1602 The findings of the present study revealed changes in fusion protein of some of the circulating field strains of SRMV in Haryana, India. 36041310 7 54 theme other 1194:1198 arg1 isolates 1207:1214 other Indian isolates 1194:1214 other Indian isolates 1194:1214 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 9 55 theme fusion 1540:1545 arg1 protein 1547:1553 fusion protein 1540:1553 fusion protein of some of the circulating field strains of SRMV 1540:1602 The findings of the present study revealed changes in fusion protein of some of the circulating field strains of SRMV in Haryana, India. 36041310 5 56 with age 775:777 arg1 mortality 791:799 higher mortality 784:799 higher mortality in young ones 784:813 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 7 57 theme phylogenetic 1056:1067 arg1 analysis 1069:1076 phylogenetic analysis 1056:1076 phylogenetic analysis 1056:1076 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 3 58 theme Chain 497:501 arg1 Reaction 503:510 Reverse Transcription Polymerase Chain Reaction 464:510 Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene 464:563 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 10 59 theme field 1718:1722 arg1 strains 1724:1730 these circulating field strains 1700:1730 these circulating field strains 1700:1730 Further detailed studies are warranted to delineate the molecular details of these circulating field strains and to evaluate the effectiveness of currently used vaccine against these mutated strains. 36041310 4 60 from mortality 631:639 arg1 outbreaks 650:658 these outbreaks 644:658 these outbreaks 644:658 The overall morbidity and cumulative mortality in these outbreaks were 37.56% and 12.09%, respectively. 36041310 1 61 theme notifiable 184:193 arg1 disease 201:207 notifiable viral disease 184:207 notifiable viral disease 184:207 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 3 62 theme gene 527:530 arg1 sequences 532:540 full gene sequences 522:540 full gene sequences of fusion protein gene 522:563 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 5 63 theme young 804:808 arg1 ones 810:813 young ones 804:813 young ones 804:813 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 10 64 theme circulating 1706:1716 arg1 strains 1724:1730 these circulating field strains 1700:1730 these circulating field strains 1700:1730 Further detailed studies are warranted to delineate the molecular details of these circulating field strains and to evaluate the effectiveness of currently used vaccine against these mutated strains. 36041310 8 65 theme vaccine 1381:1387 arg1 strain 1389:1394 reference vaccine strain 1371:1394 reference vaccine strain 1371:1394 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 4 66 theme overall 598:604 arg1 % 670:670 37.56% 665:670 37.56% 665:670 The overall morbidity and cumulative mortality in these outbreaks were 37.56% and 12.09%, respectively. 36041310 4 66 theme overall 598:604 arg1 morbidity 606:614 overall morbidity 598:614 overall morbidity 598:614 The overall morbidity and cumulative mortality in these outbreaks were 37.56% and 12.09%, respectively. 36041310 7 67 dep sequencing 1041:1050 arg1 The 1037:1039 The 1037:1039 The 1037:1039 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 8 68 link N-linked 1439:1446 arg1 sites 1462:1466 four N-linked glycosylation sites 1434:1466 four N-linked glycosylation sites instead of three 1434:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 68 link N-linked 1439:1446 arg1 three 1479:1483 three 1479:1483 three 1479:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 1 69 theme sheep 212:216 arg1 petitis 119:125 Peste des petitis ruminants 109:135 Peste des petitis ruminants 109:135 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 1 69 theme sheep 212:216 arg1 transboundary 166:178 an economically important transboundary 140:178 an economically important transboundary 140:178 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 1 69 theme sheep 212:216 arg1 disease 201:207 notifiable viral disease 184:207 notifiable viral disease 184:207 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 6 70 theme significant 894:904 arg1 difference 906:915 significant difference 894:915 significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals 894:1003 Analysis of the vaccination status revealed significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals as compared to vaccinated ones. 36041310 3 71 theme protein 552:558 arg1 gene 560:563 fusion protein gene 545:563 fusion protein gene 545:563 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 1 72 theme Peste 109:113 arg1 petitis 119:125 Peste des petitis ruminants 109:135 Peste des petitis ruminants 109:135 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 1 72 theme Peste 109:113 arg1 transboundary 166:178 an economically important transboundary 140:178 an economically important transboundary 140:178 Peste des petitis ruminants is an economically important transboundary and notifiable viral disease of sheep and goats. 36041310 0 73 from Epidemiology 0:11 arg1 India 102:106 India 102:106 India 102:106 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 0 73 from Epidemiology 0:11 arg1 Haryana 93:99 Haryana 93:99 Haryana 93:99 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 6 74 theme status 878:883 arg1 Analysis 850:857 Analysis 850:857 Analysis of the vaccination status 850:883 Analysis of the vaccination status revealed significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals as compared to vaccinated ones. 36041310 8 75 theme lineage 1406:1412 arg1 strains 1417:1423 other lineage IV strains 1400:1423 other lineage IV strains 1400:1423 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 2 76 dep July 355:358 arg1 to 365:366 to 365:366 to 365:366 In this study, 14 PPR suspected outbreaks among sheep and goats were investigated in four districts of Haryana, India, during July 2020 to October, 2021. 36041310 2 76 dep July 355:358 arg1 October 368:374 October 368:374 October 368:374 In this study, 14 PPR suspected outbreaks among sheep and goats were investigated in four districts of Haryana, India, during July 2020 to October, 2021. 36041310 6 77 theme un-vaccinated 983:995 arg1 animals 997:1003 un-vaccinated animals 983:1003 un-vaccinated animals 983:1003 Analysis of the vaccination status revealed significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals as compared to vaccinated ones. 36041310 8 78 theme amino 1285:1289 arg1 sequence 1301:1308 deduced amino acid (aa) sequence 1277:1308 deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains 1277:1364 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 0 79 theme ruminant 67:74 arg1 morbillivirus 76:88 small ruminant morbillivirus 61:88 small ruminant morbillivirus 61:88 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 0 80 from factors 19:25 arg1 India 102:106 India 102:106 India 102:106 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 0 80 from factors 19:25 arg1 Haryana 93:99 Haryana 93:99 Haryana 93:99 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 2 81 dep suspected 251:259 arg1 PPR 247:249 14 PPR 244:249 14 PPR 244:249 In this study, 14 PPR suspected outbreaks among sheep and goats were investigated in four districts of Haryana, India, during July 2020 to October, 2021. 36041310 8 82 theme glycosylation 1448:1460 arg1 sites 1462:1466 four N-linked glycosylation sites 1434:1466 four N-linked glycosylation sites instead of three 1434:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 82 theme glycosylation 1448:1460 arg1 three 1479:1483 three 1479:1483 three 1479:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 83 theme deduced 1277:1283 arg1 sequence 1301:1308 deduced amino acid (aa) sequence 1277:1308 deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains 1277:1364 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 5 84 theme factor 703:708 arg1 analysis 710:717 Risk factor analysis 698:717 Risk factor analysis 698:717 Risk factor analysis identified significant difference in mortality based on age with higher mortality in young ones; 21% as compared to adults; 7.55%. 36041310 8 85 theme three 1479:1483 arg1 sites 1462:1466 four N-linked glycosylation sites 1434:1466 four N-linked glycosylation sites instead of three 1434:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 85 theme three 1479:1483 arg1 three 1479:1483 three 1479:1483 three 1479:1483 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 8 86 theme acid 1291:1294 arg1 sequence 1301:1308 deduced amino acid (aa) sequence 1277:1308 deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains 1277:1364 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 7 87 theme study 1145:1149 arg1 strains 1122:1128 the strains 1118:1128 the strains of the present study 1118:1149 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 8 88 theme aa 1297:1298 arg1 sequence 1301:1308 deduced amino acid (aa) sequence 1277:1308 deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains 1277:1364 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 3 89 theme causative 387:395 arg1 agent 397:401 The causative agent 383:401 The causative agent of the disease; small ruminant morbillivirus 383:446 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 9 90 theme study 1514:1518 arg1 findings 1490:1497 The findings 1486:1497 The findings of the present study 1486:1518 The findings of the present study revealed changes in fusion protein of some of the circulating field strains of SRMV in Haryana, India. 36041310 6 91 from difference 906:915 arg1 mortality 934:942 mortality 934:942 mortality 934:942 Analysis of the vaccination status revealed significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals as compared to vaccinated ones. 36041310 6 91 from difference 906:915 arg1 morbidity 920:928 morbidity 920:928 morbidity 920:928 Analysis of the vaccination status revealed significant difference in morbidity and mortality with higher morbidity and mortality in un-vaccinated animals as compared to vaccinated ones. 36041310 8 92 theme sequence 1301:1308 arg1 analysis 1310:1317 deduced amino acid (aa) sequence analysis 1277:1317 deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains 1277:1364 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 10 93 theme molecular 1679:1687 arg1 details 1689:1695 the molecular details 1675:1695 the molecular details of these circulating field strains 1675:1730 Further detailed studies are warranted to delineate the molecular details of these circulating field strains and to evaluate the effectiveness of currently used vaccine against these mutated strains. 36041310 3 94 theme small 419:423 arg1 morbillivirus 434:446 small ruminant morbillivirus 419:446 The causative agent of the disease; small ruminant morbillivirus 383:446 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 0 95 theme molecular 31:39 arg1 characterization 41:56 molecular characterization 31:56 molecular characterization 31:56 Epidemiology, risk factors and molecular characterization of small ruminant morbillivirus in Haryana, India. 36041310 10 96 theme vaccine 1784:1790 arg1 effectiveness 1752:1764 the effectiveness 1748:1764 the effectiveness of currently used vaccine against these mutated strains 1748:1820 Further detailed studies are warranted to delineate the molecular details of these circulating field strains and to evaluate the effectiveness of currently used vaccine against these mutated strains. 36041310 3 97 theme disease 410:416 arg1 agent 397:401 The causative agent 383:401 The causative agent of the disease; small ruminant morbillivirus 383:446 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 3 98 dep agent 397:401 arg1 morbillivirus 434:446 small ruminant morbillivirus 419:446 The causative agent of the disease; small ruminant morbillivirus 383:446 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 36041310 8 99 theme protein 1329:1335 arg1 analysis 1310:1317 deduced amino acid (aa) sequence analysis 1277:1317 deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains 1277:1364 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 10 100 theme Further 1623:1629 arg1 studies 1640:1646 Further detailed studies 1623:1646 Further detailed studies 1623:1646 Further detailed studies are warranted to delineate the molecular details of these circulating field strains and to evaluate the effectiveness of currently used vaccine against these mutated strains. 36041310 8 101 theme circulating 1340:1350 arg1 strains 1358:1364 circulating field strains 1340:1364 circulating field strains 1340:1364 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 7 102 theme Indian 1200:1205 arg1 isolates 1207:1214 other Indian isolates 1194:1214 other Indian isolates 1194:1214 The sequencing and phylogenetic analysis of representative samples revealed that the strains of the present study fall in lineage IV (96.6-99.1%) along with other Indian isolates but made a separate cluster (sub-lineage). 36041310 8 103 theme strains 1358:1364 arg1 protein 1329:1335 fusion protein 1322:1335 fusion protein of circulating field strains 1322:1364 The comparison of deduced amino acid (aa) sequence analysis of fusion protein of circulating field strains with reference vaccine strain and other lineage IV strains revealed four N-linked glycosylation sites instead of three. 36041310 3 104 theme Polymerase 486:495 arg1 Reaction 503:510 Reverse Transcription Polymerase Chain Reaction 464:510 Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene 464:563 The causative agent of the disease; small ruminant morbillivirus was detected by Reverse Transcription Polymerase Chain Reaction targeting full gene sequences of fusion protein gene and confirmed by sequencing. 35482787 13 0 theme extracellular 1916:1928 arg1 targets 1930:1936 potential extracellular targets 1906:1936 potential extracellular targets of S. Typhimurium chitinases 1906:1965 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 13 0 theme extracellular 1916:1928 arg1 glycans 1895:1901 specific N-acetylglucosamine-containing glycans 1855:1901 specific N-acetylglucosamine-containing glycans 1855:1901 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 10 1 theme intestinal 1443:1452 arg1 tissue 1454:1459 small intestinal tissue 1437:1459 small intestinal tissue 1437:1459 In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. 35482787 7 2 theme purified 894:901 arg1 subunits 929:936 purified ChiA cleaved carbohydrate subunits 894:936 purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins 894:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 4 3 theme Typhimurium 612:622 arg1 pathogenesis 624:635 S. Typhimurium pathogenesis 609:635 S. Typhimurium pathogenesis 609:635 However, the role of these chitinases during S. Typhimurium pathogenesis is unknown. 35482787 11 4 theme reduced 1467:1473 arg1 invasion 1475:1482 This reduced invasion 1462:1482 This reduced invasion 1462:1482 This reduced invasion resulted in significantly delayed S. Typhimurium dissemination to the spleen and the liver, but chitinases were not required for systemic survival. 35482787 13 5 theme N-acetylglucosamine-containing 1864:1893 arg1 targets 1930:1936 potential extracellular targets 1906:1936 potential extracellular targets of S. Typhimurium chitinases 1906:1965 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 13 5 theme N-acetylglucosamine-containing 1864:1893 arg1 glycans 1895:1901 specific N-acetylglucosamine-containing glycans 1855:1901 specific N-acetylglucosamine-containing glycans 1855:1901 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 5 6 theme putative 653:660 arg1 STM0233 672:678 The putative chitinase STM0233 649:678 The putative chitinase STM0233 649:678 The putative chitinase STM0233 has not been studied previously, and only limited data exists on ChiA. 35482787 9 7 theme % 1235:1235 arg1 reduction 1237:1245 a 70% reduction 1231:1245 a 70% reduction in invasion of small intestinal epithelial cells 1231:1294 S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. 35482787 14 8 theme Lewis 2024:2028 arg1 result 2070:2075 a result 2068:2075 a result of host cell modulation due to the detection of S. Typhimurium chitinases 2068:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 14 8 theme Lewis 2024:2028 arg1 glycans 2045:2051 Lewis X/A-containing glycans 2024:2051 Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases 2024:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 7 9 attach present 938:944 arg2 subunits 929:936 purified ChiA cleaved carbohydrate subunits 894:936 purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins 894:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 7 9 attach present 938:944 arg1 glycoproteins 967:979 mammalian surface glycoproteins 949:979 mammalian surface glycoproteins 949:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 13 10 theme intestinal 1823:1832 arg1 cells 1834:1838 small intestinal cells 1817:1838 small intestinal cells 1817:1838 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 1 11 theme leading 193:199 arg1 causes 201:206 the leading causes 189:206 the leading causes of food-borne illnesses worldwide 189:240 Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. 35482787 15 12 theme Similar 2152:2158 arg1 changes 2169:2175 Similar glycomic changes 2152:2175 Similar glycomic changes elicited by chitinase deficient strains 2152:2215 Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. 35482787 2 13 theme virulence 316:324 arg1 factors 326:332 multiple virulence factors 307:332 multiple virulence factors that facilitate cellular invasion 307:366 To colonize the gastrointestinal tract, S. Typhimurium produces multiple virulence factors that facilitate cellular invasion. 35482787 7 14 theme chiA 841:844 arg1 expression 846:855 chiA expression 841:855 chiA expression 841:855 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 16 15 theme host 2404:2407 arg1 glycome 2409:2415 the host glycome 2400:2415 the host glycome 2400:2415 Overall, our results demonstrate that S. Typhimurium chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome. 35482787 12 16 theme strain 1679:1684 arg1 defect 1645:1650 The invasion defect 1632:1650 The invasion defect of the chitinase-deficient strain 1632:1684 The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type S. Typhimurium, suggesting that chitinases are secreted. 35482787 13 17 theme N-linked 1797:1804 arg1 glycans 1806:1812 N-linked glycans 1797:1812 N-linked glycans of small intestinal cells 1797:1838 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 9 18 theme intestinal 1268:1277 arg1 cells 1290:1294 small intestinal epithelial cells 1262:1294 small intestinal epithelial cells 1262:1294 S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. 35482787 1 19 theme illnesses 222:230 arg1 worldwide 232:240 food-borne illnesses worldwide 211:240 food-borne illnesses worldwide 211:240 Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. 35482787 3 20 contain contains 501:508 arg1 genome 494:499 the S. Typhimurium genome 475:499 the S. Typhimurium genome 475:499 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 20 contain contains 501:508 arg2 STM0233 555:561 STM0233 555:561 STM0233 555:561 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 20 contain contains 501:508 arg2 STM0018 536:542 STM0018 536:542 STM0018 (chiA) 536:549 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 20 contain contains 501:508 arg2 chitinases 524:533 two annotated chitinases 510:533 two annotated chitinases: STM0018 (chiA) and STM0233 510:561 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 20 contain contains 501:508 arg2 factors 421:427 virulence factors 411:427 virulence factors for various pathogenic bacterial species 411:468 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 9 21 theme cells 1290:1294 arg1 invasion 1250:1257 invasion 1250:1257 invasion of small intestinal epithelial cells 1250:1294 S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. 35482787 10 22 dep S. 1360:1361 arg1 Typhimurium 1363:1373 Typhimurium 1363:1373 Typhimurium 1363:1373 In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. 35482787 11 23 dep S. 1518:1519 arg1 Typhimurium 1521:1531 Typhimurium 1521:1531 Typhimurium 1521:1531 This reduced invasion resulted in significantly delayed S. Typhimurium dissemination to the spleen and the liver, but chitinases were not required for systemic survival. 35482787 8 24 theme chiA 1061:1064 arg1 expression 1047:1056 expression 1047:1056 expression of chiA and STM0233 1047:1076 Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. 35482787 1 25 dep Typhimurium 150:160 arg1 Typhimurium 166:176 S. Typhimurium 163:176 S. Typhimurium 163:176 Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. 35482787 14 26 theme cell 2085:2088 arg1 modulation 2090:2099 host cell modulation 2080:2099 host cell modulation due to the detection of S. Typhimurium chitinases 2080:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 0 27 theme intestinal 101:110 arg1 invasion 112:119 small intestinal invasion 95:119 small intestinal invasion 95:119 Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion. 35482787 8 28 theme STM0233 1070:1076 arg1 expression 1047:1056 expression 1047:1056 expression of chiA and STM0233 1047:1076 Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. 35482787 3 29 dep chitinases 524:533 arg1 chiA 545:548 chiA 545:548 chiA 545:548 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 29 dep chitinases 524:533 arg1 STM0233 555:561 STM0233 555:561 STM0233 555:561 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 29 dep chitinases 524:533 arg1 STM0018 536:542 STM0018 536:542 STM0018 (chiA) 536:549 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 29 dep chitinases 524:533 arg1 chitinases 524:533 two annotated chitinases 510:533 two annotated chitinases: STM0018 (chiA) and STM0233 510:561 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 10 30 theme gastroenteritis 1311:1325 arg1 model 1333:1337 a gastroenteritis mouse model 1309:1337 a gastroenteritis mouse model 1309:1337 In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. 35482787 12 31 theme Typhimurium 1730:1740 arg1 presence 1705:1712 the presence 1701:1712 the presence of wild-type S. Typhimurium 1701:1740 The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type S. Typhimurium, suggesting that chitinases are secreted. 35482787 6 32 from vertebrates 819:829 arg1 absent 809:814 absent 809:814 absent 809:814 Chitinases typically hydrolyze chitin polymers, which are absent in vertebrates. 35482787 7 33 theme surface 959:965 arg1 glycoproteins 967:979 mammalian surface glycoproteins 949:979 mammalian surface glycoproteins 949:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 14 34 theme due 2101:2103 arg1 modulation 2090:2099 host cell modulation 2080:2099 host cell modulation due to the detection of S. Typhimurium chitinases 2080:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 7 35 located detected 861:868 arg1 models 883:888 infection models 873:888 infection models 873:888 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 7 35 located detected 861:868 arg1 subunits 929:936 purified ChiA cleaved carbohydrate subunits 894:936 purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins 894:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 7 35 located detected 861:868 arg2 expression 846:855 chiA expression 841:855 chiA expression 841:855 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 10 36 theme chitinase-deficient 1340:1358 arg1 strains 1375:1381 chitinase-deficient S. Typhimurium strains 1340:1381 chitinase-deficient S. Typhimurium strains 1340:1381 In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. 35482787 13 37 theme Typhimurium 1944:1954 arg1 chitinases 1956:1965 S. Typhimurium chitinases 1941:1965 S. Typhimurium chitinases 1941:1965 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 3 38 theme bacterial 452:460 arg1 species 462:468 various pathogenic bacterial species 433:468 various pathogenic bacterial species 433:468 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 11 39 theme S. 1518:1519 arg1 dissemination 1533:1545 significantly delayed S. Typhimurium dissemination 1496:1545 significantly delayed S. Typhimurium dissemination to the spleen and the liver 1496:1573 This reduced invasion resulted in significantly delayed S. Typhimurium dissemination to the spleen and the liver, but chitinases were not required for systemic survival. 35482787 3 40 theme Typhimurium 482:492 arg1 genome 494:499 the S. Typhimurium genome 475:499 the S. Typhimurium genome 475:499 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 6 41 from absent 809:814 arg1 vertebrates 819:829 vertebrates 819:829 vertebrates 819:829 Chitinases typically hydrolyze chitin polymers, which are absent in vertebrates. 35482787 3 42 theme various 433:439 arg1 species 462:468 various pathogenic bacterial species 433:468 various pathogenic bacterial species 433:468 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 13 43 link N-linked 1797:1804 arg1 glycans 1806:1812 N-linked glycans 1797:1812 N-linked glycans of small intestinal cells 1797:1838 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 14 44 theme chitinases 2140:2149 arg1 detection 2112:2120 the detection 2108:2120 the detection of S. Typhimurium chitinases 2108:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 3 45 theme annotated 514:522 arg1 factors 421:427 virulence factors 411:427 virulence factors for various pathogenic bacterial species 411:468 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 45 theme annotated 514:522 arg1 STM0233 555:561 STM0233 555:561 STM0233 555:561 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 45 theme annotated 514:522 arg1 STM0018 536:542 STM0018 536:542 STM0018 (chiA) 536:549 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 45 theme annotated 514:522 arg1 chitinases 524:533 two annotated chitinases 510:533 two annotated chitinases: STM0018 (chiA) and STM0233 510:561 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 7 46 theme mammalian 949:957 arg1 glycoproteins 967:979 mammalian surface glycoproteins 949:979 mammalian surface glycoproteins 949:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 1 47 theme worldwide 232:240 arg1 causes 201:206 the leading causes 189:206 the leading causes of food-borne illnesses worldwide 189:240 Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. 35482787 8 48 theme epithelial 1146:1155 arg1 adhesion 1162:1169 epithelial cell adhesion 1146:1169 epithelial cell adhesion 1146:1169 Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. 35482787 16 49 theme Typhimurium 2308:2318 arg1 chitinases 2320:2329 S. Typhimurium chitinases 2305:2329 S. Typhimurium chitinases 2305:2329 Overall, our results demonstrate that S. Typhimurium chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome. 35482787 7 50 theme present 938:944 arg1 subunits 929:936 purified ChiA cleaved carbohydrate subunits 894:936 purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins 894:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 14 51 theme glycans 2045:2051 arg1 abundance 2011:2019 a differential abundance 1996:2019 a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases 1996:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 13 52 theme potential 1906:1914 arg1 targets 1930:1936 potential extracellular targets 1906:1936 potential extracellular targets of S. Typhimurium chitinases 1906:1965 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 13 52 theme potential 1906:1914 arg1 glycans 1895:1901 specific N-acetylglucosamine-containing glycans 1855:1901 specific N-acetylglucosamine-containing glycans 1855:1901 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 7 53 theme carbohydrate 916:927 arg1 subunits 929:936 purified ChiA cleaved carbohydrate subunits 894:936 purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins 894:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 13 54 theme S. 1941:1942 arg1 chitinases 1956:1965 S. Typhimurium chitinases 1941:1965 S. Typhimurium chitinases 1941:1965 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 4 55 theme chitinases 591:600 arg1 role 577:580 the role 573:580 the role of these chitinases during S. Typhimurium pathogenesis 573:635 However, the role of these chitinases during S. Typhimurium pathogenesis is unknown. 35482787 4 55 theme chitinases 591:600 arg1 unknown 640:646 unknown 640:646 unknown 640:646 However, the role of these chitinases during S. Typhimurium pathogenesis is unknown. 35482787 16 56 theme intestinal 2345:2354 arg1 adhesion 2356:2363 intestinal adhesion 2345:2363 intestinal adhesion 2345:2363 Overall, our results demonstrate that S. Typhimurium chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome. 35482787 10 57 theme small 1437:1441 arg1 tissue 1454:1459 small intestinal tissue 1437:1459 small intestinal tissue 1437:1459 In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. 35482787 2 58 theme multiple 307:314 arg1 factors 326:332 multiple virulence factors 307:332 multiple virulence factors that facilitate cellular invasion 307:366 To colonize the gastrointestinal tract, S. Typhimurium produces multiple virulence factors that facilitate cellular invasion. 35482787 7 59 theme ChiA 903:906 arg1 subunits 929:936 purified ChiA cleaved carbohydrate subunits 894:936 purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins 894:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 4 60 theme S. 609:610 arg1 pathogenesis 624:635 S. Typhimurium pathogenesis 609:635 S. Typhimurium pathogenesis 609:635 However, the role of these chitinases during S. Typhimurium pathogenesis is unknown. 35482787 13 61 theme specific 1855:1862 arg1 targets 1930:1936 potential extracellular targets 1906:1936 potential extracellular targets of S. Typhimurium chitinases 1906:1965 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 13 61 theme specific 1855:1862 arg1 glycans 1895:1901 specific N-acetylglucosamine-containing glycans 1855:1901 specific N-acetylglucosamine-containing glycans 1855:1901 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 9 62 theme 70 1233:1234 arg1 % 1235:1235 % 1235:1235 % 1235:1235 S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. 35482787 14 63 theme X/A-containing 2030:2043 arg1 result 2070:2075 a result 2068:2075 a result of host cell modulation due to the detection of S. Typhimurium chitinases 2068:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 14 63 theme X/A-containing 2030:2043 arg1 glycans 2045:2051 Lewis X/A-containing glycans 2024:2051 Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases 2024:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 13 64 theme small 1817:1821 arg1 cells 1834:1838 small intestinal cells 1817:1838 small intestinal cells 1817:1838 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 5 65 theme chitinase 662:670 arg1 STM0233 672:678 The putative chitinase STM0233 649:678 The putative chitinase STM0233 649:678 The putative chitinase STM0233 has not been studied previously, and only limited data exists on ChiA. 35482787 7 66 theme infection 873:881 arg1 models 883:888 infection models 873:888 infection models 873:888 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 12 67 theme chitinase-deficient 1659:1677 arg1 strain 1679:1684 the chitinase-deficient strain 1655:1684 the chitinase-deficient strain 1655:1684 The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type S. Typhimurium, suggesting that chitinases are secreted. 35482787 13 68 theme cells 1834:1838 arg1 glycans 1806:1812 N-linked glycans 1797:1812 N-linked glycans of small intestinal cells 1797:1838 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 5 69 theme limited 722:728 arg1 data 730:733 only limited data 717:733 only limited data 717:733 The putative chitinase STM0233 has not been studied previously, and only limited data exists on ChiA. 35482787 10 70 theme tissue 1454:1459 arg1 invasion 1425:1432 the invasion 1421:1432 the invasion of small intestinal tissue 1421:1459 In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. 35482787 1 71 theme causes 201:206 arg1 one 182:184 one 182:184 one 182:184 Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. 35482787 1 71 theme causes 201:206 arg1 causes 201:206 the leading causes 189:206 the leading causes of food-borne illnesses worldwide 189:240 Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. 35482787 16 72 theme glycome 2409:2415 arg1 modulation 2386:2395 modulation 2386:2395 modulation of the host glycome 2386:2415 Overall, our results demonstrate that S. Typhimurium chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome. 35482787 9 73 theme small 1262:1266 arg1 cells 1290:1294 small intestinal epithelial cells 1262:1294 small intestinal epithelial cells 1262:1294 S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. 35482787 1 74 theme food-borne 211:220 arg1 worldwide 232:240 food-borne illnesses worldwide 211:240 food-borne illnesses worldwide 211:240 Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. 35482787 12 75 theme invasion 1636:1643 arg1 defect 1645:1650 The invasion defect 1632:1650 The invasion defect of the chitinase-deficient strain 1632:1684 The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type S. Typhimurium, suggesting that chitinases are secreted. 35482787 9 76 theme epithelial 1279:1288 arg1 cells 1290:1294 small intestinal epithelial cells 1262:1294 small intestinal epithelial cells 1262:1294 S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. 35482787 11 77 theme systemic 1613:1620 arg1 survival 1622:1629 systemic survival 1613:1629 systemic survival 1613:1629 This reduced invasion resulted in significantly delayed S. Typhimurium dissemination to the spleen and the liver, but chitinases were not required for systemic survival. 35482787 9 78 from reduction 1237:1245 arg1 invasion 1250:1257 invasion 1250:1257 invasion of small intestinal epithelial cells 1250:1294 S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. 35482787 2 79 theme gastrointestinal 259:274 arg1 tract 276:280 the gastrointestinal tract 255:280 the gastrointestinal tract 255:280 To colonize the gastrointestinal tract, S. Typhimurium produces multiple virulence factors that facilitate cellular invasion. 35482787 14 80 theme differential 1998:2009 arg1 abundance 2011:2019 a differential abundance 1996:2019 a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases 1996:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 0 81 theme small 95:99 arg1 invasion 112:119 small intestinal invasion 95:119 small intestinal invasion 95:119 Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion. 35482787 14 82 theme S. 2125:2126 arg1 chitinases 2140:2149 S. Typhimurium chitinases 2125:2149 S. Typhimurium chitinases 2125:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 10 83 theme mouse 1327:1331 arg1 model 1333:1337 a gastroenteritis mouse model 1309:1337 a gastroenteritis mouse model 1309:1337 In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. 35482787 13 84 theme chitinases 1956:1965 arg1 targets 1930:1936 potential extracellular targets 1906:1936 potential extracellular targets of S. Typhimurium chitinases 1906:1965 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 13 84 theme chitinases 1956:1965 arg1 glycans 1895:1901 specific N-acetylglucosamine-containing glycans 1855:1901 specific N-acetylglucosamine-containing glycans 1855:1901 By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. 35482787 15 85 theme glycomic 2160:2167 arg1 changes 2169:2175 Similar glycomic changes 2152:2175 Similar glycomic changes elicited by chitinase deficient strains 2152:2215 Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. 35482787 3 86 theme S. 479:480 arg1 genome 494:499 the S. Typhimurium genome 475:499 the S. Typhimurium genome 475:499 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 8 87 theme mouse 1100:1104 arg1 gut 1106:1108 the mouse gut 1096:1108 the mouse gut 1096:1108 Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. 35482787 10 88 theme S. 1360:1361 arg1 strains 1375:1381 chitinase-deficient S. Typhimurium strains 1340:1381 chitinase-deficient S. Typhimurium strains 1340:1381 In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. 35482787 0 89 theme Typhimurium 28:38 arg1 chitinases 40:49 Salmonella enterica serovar Typhimurium chitinases 0:49 Salmonella enterica serovar Typhimurium chitinases 0:49 Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion. 35482787 14 90 theme modulation 2090:2099 arg1 result 2070:2075 a result 2068:2075 a result of host cell modulation due to the detection of S. Typhimurium chitinases 2068:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 14 90 theme modulation 2090:2099 arg1 glycans 2045:2051 Lewis X/A-containing glycans 2024:2051 Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases 2024:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 3 91 theme virulence 411:419 arg1 factors 421:427 virulence factors 411:427 virulence factors for various pathogenic bacterial species 411:468 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 3 91 theme virulence 411:419 arg1 chitinases 524:533 two annotated chitinases 510:533 two annotated chitinases: STM0018 (chiA) and STM0233 510:561 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 11 92 theme delayed 1510:1516 arg1 dissemination 1533:1545 significantly delayed S. Typhimurium dissemination 1496:1545 significantly delayed S. Typhimurium dissemination to the spleen and the liver 1496:1573 This reduced invasion resulted in significantly delayed S. Typhimurium dissemination to the spleen and the liver, but chitinases were not required for systemic survival. 35482787 15 93 theme chitinases 2255:2264 arg1 redundancy 2237:2246 functional redundancy 2226:2246 functional redundancy of the chitinases 2226:2264 Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. 35482787 14 94 theme host 2080:2083 arg1 modulation 2090:2099 host cell modulation 2080:2099 host cell modulation due to the detection of S. Typhimurium chitinases 2080:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 0 95 theme intestinal 64:73 arg1 glycome 75:81 the intestinal glycome 60:81 the intestinal glycome 60:81 Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion. 35482787 15 96 theme functional 2226:2235 arg1 redundancy 2237:2246 functional redundancy 2226:2246 functional redundancy of the chitinases 2226:2264 Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. 35482787 3 97 theme pathogenic 441:450 arg1 species 462:468 various pathogenic bacterial species 433:468 various pathogenic bacterial species 433:468 Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. 35482787 6 98 theme chitin 782:787 arg1 polymers 789:796 chitin polymers 782:796 chitin polymers 782:796 Chitinases typically hydrolyze chitin polymers, which are absent in vertebrates. 35482787 15 99 theme deficient 2199:2207 arg1 strains 2209:2215 chitinase deficient strains 2189:2215 chitinase deficient strains 2189:2215 Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. 35482787 8 100 theme cell 1157:1160 arg1 adhesion 1162:1169 epithelial cell adhesion 1146:1169 epithelial cell adhesion 1146:1169 Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. 35482787 14 101 theme Typhimurium 2128:2138 arg1 chitinases 2140:2149 S. Typhimurium chitinases 2125:2149 S. Typhimurium chitinases 2125:2149 This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. 35482787 2 102 theme cellular 350:357 arg1 invasion 359:366 cellular invasion 350:366 cellular invasion 350:366 To colonize the gastrointestinal tract, S. Typhimurium produces multiple virulence factors that facilitate cellular invasion. 35482787 15 103 theme chitinase 2189:2197 arg1 strains 2209:2215 chitinase deficient strains 2189:2215 chitinase deficient strains 2189:2215 Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. 35482787 7 104 gly glycoproteins 967:979 arg1 glycoproteins 967:979 mammalian surface glycoproteins 949:979 mammalian surface glycoproteins 949:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35482787 16 105 theme S. 2305:2306 arg1 chitinases 2320:2329 S. Typhimurium chitinases 2305:2329 S. Typhimurium chitinases 2305:2329 Overall, our results demonstrate that S. Typhimurium chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome. 35482787 7 106 theme cleaved 908:914 arg1 subunits 929:936 purified ChiA cleaved carbohydrate subunits 894:936 purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins 894:979 However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. 35367457 0 0 theme mannosyltransferase 88:106 arg1 bus-8 108:112 mannosyltransferase bus-8 88:112 mannosyltransferase bus-8 88:112 C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8. 35367457 7 1 theme GM2 1130:1132 arg1 domain 1148:1153 a ganglioside GM2 lipid-binding domain 1116:1153 a ganglioside GM2 lipid-binding domain 1116:1153 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 1 2 theme extracellular 171:183 arg1 barrier 215:221 a protective barrier 202:221 a protective barrier from the external environment 202:251 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 1 2 theme extracellular 171:183 arg1 aECM 193:196 aECM 193:196 aECM 193:196 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 1 2 theme extracellular 171:183 arg1 matrix 185:190 apical extracellular matrix 164:190 apical extracellular matrix (aECM) 164:197 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 4 3 from development 633:643 arg1 C. elegans 648:657 C. elegans 648:657 C. elegans 648:657 Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. 35367457 7 4 theme ganglioside 1118:1128 arg1 domain 1148:1153 a ganglioside GM2 lipid-binding domain 1116:1153 a ganglioside GM2 lipid-binding domain 1116:1153 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 7 5 theme lipid-binding 1134:1146 arg1 domain 1148:1153 a ganglioside GM2 lipid-binding domain 1116:1153 a ganglioside GM2 lipid-binding domain 1116:1153 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 5 6 theme adult 899:903 arg1 cells 915:919 adult epidermal cells 899:919 adult epidermal cells 899:919 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 4 7 theme aECM 725:728 arg1 remodeling 730:739 aECM remodeling 725:739 aECM remodeling 725:739 Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. 35367457 6 8 theme mlt-8 1003:1007 arg1 reduction 981:989 reduction 981:989 reduction of bus-8 or mlt-8 981:1007 The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. 35367457 11 9 from expression 1669:1678 arg1 epidermis 1705:1713 the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition 1701:1859 the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition 1701:1859 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 10 10 theme BUS-8-mediated 1532:1545 arg1 glycosylation 1547:1559 BUS-8-mediated glycosylation 1532:1559 BUS-8-mediated glycosylation of MLT-8 1532:1568 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 35367457 11 11 from glycosylation 1684:1696 arg1 epidermis 1705:1713 the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition 1701:1859 the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition 1701:1859 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 10 12 theme signaling 1596:1604 arg1 cue 1606:1608 a molting signaling cue 1586:1608 a molting signaling cue 1586:1608 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 35367457 10 12 theme signaling 1596:1604 arg1 stability 1471:1479 MLT-8 stability 1465:1479 MLT-8 stability 1465:1479 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 35367457 4 13 theme epidermal 623:631 arg1 development 633:643 epidermal development 623:643 epidermal development in C. elegans 623:657 Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. 35367457 0 14 theme bus-8 108:112 arg1 expression 74:83 expression 74:83 expression of mannosyltransferase bus-8 74:112 C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8. 35367457 3 15 dep whether 410:416 arg1 impact 449:454 impact 449:454 impact 449:454 How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. 35367457 6 16 theme morphological 943:955 arg1 defect 957:962 The apical epidermal morphological defect 922:962 The apical epidermal morphological defect 922:962 The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. 35367457 4 17 theme remodeling 730:739 arg1 downregulation 707:720 downregulation 707:720 downregulation of aECM remodeling 707:739 Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. 35367457 6 18 theme bus-8 994:998 arg1 reduction 981:989 reduction 981:989 reduction of bus-8 or mlt-8 981:1007 The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. 35367457 0 19 theme signal 126:131 arg1 mlt-8 133:137 signal mlt-8 126:137 signal mlt-8 126:137 C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8. 35367457 8 20 theme mlt-8 1291:1295 arg1 Overexpression 1264:1277 Overexpression 1264:1277 Overexpression of bus-8 or mlt-8 1264:1295 Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. 35367457 8 21 theme blmp-1 1352:1357 arg1 mutants 1359:1365 blmp-1 mutants 1352:1365 blmp-1 mutants 1352:1365 Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. 35367457 7 22 gly glycoproteins 1091:1103 arg1 glycoproteins 1091:1103 N-linked glycoproteins 1082:1103 N-linked glycoproteins 1082:1103 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 3 23 theme epidermal 456:464 arg1 morphology 471:480 epidermal cell morphology 456:480 epidermal cell morphology 456:480 How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. 35367457 5 24 theme genes 780:784 arg1 upregulation 764:775 upregulation 764:775 upregulation of genes essential for molting, including bus-8 and mlt-8, 764:834 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 10 25 theme aECM 1613:1616 arg1 remodeling 1618:1627 aECM remodeling 1613:1627 aECM remodeling 1613:1627 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 35367457 9 26 theme fusion 1379:1384 arg1 protein 1386:1392 MLT-8::GFP fusion protein 1368:1392 MLT-8::GFP fusion protein 1368:1392 MLT-8::GFP fusion protein is localized to lysosomes and secreted to aECM. 35367457 3 27 theme cell 466:469 arg1 morphology 471:480 epidermal cell morphology 456:480 epidermal cell morphology 456:480 How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. 35367457 10 28 theme molting 1588:1594 arg1 cue 1606:1608 a molting signaling cue 1586:1608 a molting signaling cue 1586:1608 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 35367457 10 28 theme molting 1588:1594 arg1 stability 1471:1479 MLT-8 stability 1465:1479 MLT-8 stability 1465:1479 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 35367457 7 29 theme old 1222:1224 arg1 cuticle 1226:1232 the old cuticle 1218:1232 the old cuticle 1218:1232 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 7 30 theme glycoproteins 1091:1103 arg1 glycosylation 1065:1077 glycosylation 1065:1077 glycosylation of N-linked glycoproteins 1065:1103 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 5 31 theme essential 786:794 arg1 genes 780:784 genes 780:784 genes 780:784 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 5 31 theme essential 786:794 arg1 bus-8 819:823 bus-8 819:823 bus-8 819:823 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 5 31 theme essential 786:794 arg1 mlt-8 829:833 mlt-8 829:833 mlt-8 829:833 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 11 32 theme MLT-8 1663:1667 arg1 expression 1669:1678 MLT-8 expression 1663:1678 MLT-8 expression 1663:1678 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 0 33 theme C. elegans 0:9 arg1 BLMP-1 11:16 C. elegans BLMP-1 0:16 C. elegans BLMP-1 0:16 C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8. 35367457 4 34 theme transcription 571:583 arg1 factor 585:590 the conserved Zn-finger transcription factor BLMP-1/Blimp1 547:604 the conserved Zn-finger transcription factor BLMP-1/Blimp1 547:604 Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. 35367457 9 35 theme MLT-8 1368:1372 arg1 protein 1386:1392 MLT-8::GFP fusion protein 1368:1392 MLT-8::GFP fusion protein 1368:1392 MLT-8::GFP fusion protein is localized to lysosomes and secreted to aECM. 35367457 2 36 theme animal 324:329 arg1 development 331:341 animal development 324:341 animal development 324:341 The aECM is highly dynamic and constantly undergoes remodeling during animal development. 35367457 4 37 theme epidermis 694:702 arg1 shape 681:685 apical cell shape 669:685 apical cell shape of the epidermis 669:702 Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. 35367457 0 38 theme apical 27:32 arg1 morphology 49:58 apical epidermal cell morphology 27:58 apical epidermal cell morphology 27:58 C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8. 35367457 4 39 theme Zn-finger 561:569 arg1 factor 585:590 the conserved Zn-finger transcription factor BLMP-1/Blimp1 547:604 the conserved Zn-finger transcription factor BLMP-1/Blimp1 547:604 Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. 35367457 10 40 theme lysosomal 1485:1493 arg1 targeting 1495:1503 lysosomal targeting 1485:1503 lysosomal targeting 1485:1503 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 35367457 8 41 theme cell 1325:1328 arg1 defect 1330:1335 an apical epidermal cell defect 1305:1335 an apical epidermal cell defect 1305:1335 Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. 35367457 9 42 theme :: 1373:1374 arg1 protein 1386:1392 MLT-8::GFP fusion protein 1368:1392 MLT-8::GFP fusion protein 1368:1392 MLT-8::GFP fusion protein is localized to lysosomes and secreted to aECM. 35367457 4 43 theme apical 669:674 arg1 shape 681:685 apical cell shape 669:685 apical cell shape of the epidermis 669:702 Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. 35367457 11 44 gly glycosylation 1684:1696 arg1 epidermis 1705:1713 the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition 1701:1859 the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition 1701:1859 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 7 45 theme N-linked 1082:1089 arg1 glycoproteins 1091:1103 N-linked glycoproteins 1082:1103 N-linked glycoproteins 1082:1103 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 7 46 gly glycosylation 1065:1077 arg1 glycoproteins 1091:1103 N-linked glycoproteins 1082:1103 N-linked glycoproteins 1082:1103 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 5 47 theme epidermal 905:913 arg1 cells 915:919 adult epidermal cells 899:919 adult epidermal cells 899:919 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 1 48 theme protective 204:213 arg1 barrier 215:221 a protective barrier 202:221 a protective barrier from the external environment 202:251 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 1 48 theme protective 204:213 arg1 matrix 185:190 apical extracellular matrix 164:190 apical extracellular matrix (aECM) 164:197 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 0 49 theme cell 44:47 arg1 morphology 49:58 apical epidermal cell morphology 27:58 apical epidermal cell morphology 27:58 C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8. 35367457 5 50 theme apical 882:887 arg1 region 889:894 the apical region 878:894 the apical region of adult epidermal cells 878:919 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 8 51 theme bus-8 1282:1286 arg1 Overexpression 1264:1277 Overexpression 1264:1277 Overexpression of bus-8 or mlt-8 1264:1295 Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. 35367457 0 52 theme epidermal 34:42 arg1 morphology 49:58 apical epidermal cell morphology 27:58 apical epidermal cell morphology 27:58 C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8. 35367457 11 53 theme cell 1812:1815 arg1 morphology 1817:1826 apical epidermal cell morphology 1795:1826 apical epidermal cell morphology 1795:1826 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 5 54 theme blmp-1 750:755 arg1 Loss 742:745 Loss 742:745 Loss of blmp-1 742:755 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 7 55 link N-linked 1082:1089 arg1 glycoproteins 1091:1103 N-linked glycoproteins 1082:1103 N-linked glycoproteins 1082:1103 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 11 56 theme inappropriate 1726:1738 arg1 remodeling 1745:1754 inappropriate aECM remodeling 1726:1754 inappropriate aECM remodeling 1726:1754 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 4 57 theme cell 676:679 arg1 shape 681:685 apical cell shape 669:685 apical cell shape of the epidermis 669:702 Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. 35367457 11 58 theme larva-to-adult 1835:1848 arg1 transition 1850:1859 larva-to-adult transition 1835:1859 larva-to-adult transition 1835:1859 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 1 59 from environment 241:251 arg1 barrier 215:221 a protective barrier 202:221 a protective barrier from the external environment 202:251 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 1 59 from environment 241:251 arg1 matrix 185:190 apical extracellular matrix 164:190 apical extracellular matrix (aECM) 164:197 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 11 60 theme epidermal 1802:1810 arg1 morphology 1817:1826 apical epidermal cell morphology 1795:1826 apical epidermal cell morphology 1795:1826 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 7 61 theme key 1021:1023 arg1 mannosyltransferase 1025:1043 a key mannosyltransferase 1019:1043 a key mannosyltransferase 1019:1043 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 7 61 theme key 1021:1023 arg1 BUS-8 1010:1014 BUS-8 1010:1014 BUS-8 1010:1014 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 5 62 theme cells 915:919 arg1 region 889:894 the apical region 878:894 the apical region of adult epidermal cells 878:919 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 10 63 theme MLT-8 1465:1469 arg1 cue 1606:1608 a molting signaling cue 1586:1608 a molting signaling cue 1586:1608 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 35367457 10 63 theme MLT-8 1465:1469 arg1 stability 1471:1479 MLT-8 stability 1465:1479 MLT-8 stability 1465:1479 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 35367457 4 64 theme conserved 551:559 arg1 factor 585:590 the conserved Zn-finger transcription factor BLMP-1/Blimp1 547:604 the conserved Zn-finger transcription factor BLMP-1/Blimp1 547:604 Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. 35367457 10 65 gly glycosylation 1547:1559 arg1 MLT-8 1564:1568 MLT-8 1564:1568 MLT-8 1564:1568 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 35367457 6 66 theme epidermal 933:941 arg1 defect 957:962 The apical epidermal morphological defect 922:962 The apical epidermal morphological defect 922:962 The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. 35367457 11 67 theme apical 1795:1800 arg1 morphology 1817:1826 apical epidermal cell morphology 1795:1826 apical epidermal cell morphology 1795:1826 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 1 68 theme Skin 140:143 arg1 epidermis 145:153 Skin epidermis 140:153 Skin epidermis 140:153 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 9 69 theme GFP 1375:1377 arg1 protein 1386:1392 MLT-8::GFP fusion protein 1368:1392 MLT-8::GFP fusion protein 1368:1392 MLT-8::GFP fusion protein is localized to lysosomes and secreted to aECM. 35367457 8 70 theme apical 1308:1313 arg1 defect 1330:1335 an apical epidermal cell defect 1305:1335 an apical epidermal cell defect 1305:1335 Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. 35367457 7 71 contain has 1112:1114 arg1 MLT-8 1106:1110 MLT-8 1106:1110 MLT-8 1106:1110 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 7 71 contain has 1112:1114 arg2 domain 1148:1153 a ganglioside GM2 lipid-binding domain 1116:1153 a ganglioside GM2 lipid-binding domain 1116:1153 BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. 35367457 1 72 theme external 232:239 arg1 environment 241:251 the external environment 228:251 the external environment 228:251 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 3 73 theme aECM 348:351 arg1 dynamics 353:360 aECM dynamics 348:360 aECM dynamics 348:360 How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. 35367457 5 74 theme abnormal 860:867 arg1 shape 869:873 an abnormal shape 857:873 an abnormal shape in the apical region of adult epidermal cells 857:919 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 8 75 theme epidermal 1315:1323 arg1 defect 1330:1335 an apical epidermal cell defect 1305:1335 an apical epidermal cell defect 1305:1335 Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. 35367457 11 76 theme morphology 1817:1826 arg1 maintenance 1780:1790 maintenance 1780:1790 maintenance of apical epidermal cell morphology 1780:1826 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 6 77 theme apical 926:931 arg1 defect 957:962 The apical epidermal morphological defect 922:962 The apical epidermal morphological defect 922:962 The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. 35367457 11 78 theme aECM 1740:1743 arg1 remodeling 1745:1754 inappropriate aECM remodeling 1726:1754 inappropriate aECM remodeling 1726:1754 We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition. 35367457 5 79 from shape 869:873 arg1 region 889:894 the apical region 878:894 the apical region of adult epidermal cells 878:919 Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. 35367457 1 80 theme apical 164:169 arg1 barrier 215:221 a protective barrier 202:221 a protective barrier from the external environment 202:251 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 1 80 theme apical 164:169 arg1 aECM 193:196 aECM 193:196 aECM 193:196 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 1 80 theme apical 164:169 arg1 matrix 185:190 apical extracellular matrix 164:190 apical extracellular matrix (aECM) 164:197 Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. 35367457 10 81 theme MLT-8 1564:1568 arg1 glycosylation 1547:1559 BUS-8-mediated glycosylation 1532:1559 BUS-8-mediated glycosylation of MLT-8 1532:1568 BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. 36209585 10 0 theme systemic 1192:1199 arg1 fibrosis 1201:1208 systemic fibrosis 1192:1208 systemic fibrosis 1192:1208 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 1 1 from protein 170:176 arg1 removal 106:112 the removal 102:112 the removal of N-linked glycans from newly synthesized or misfolded protein 102:176 N-glycanase 1(NGLY1) catalyzes the removal of N-linked glycans from newly synthesized or misfolded protein. 36209585 1 2 theme synthesized 145:155 arg1 protein 170:176 newly synthesized or misfolded protein 139:176 newly synthesized or misfolded protein 139:176 N-glycanase 1(NGLY1) catalyzes the removal of N-linked glycans from newly synthesized or misfolded protein. 36209585 1 3 link N-linked 117:124 arg1 glycans 126:132 N-linked glycans 117:132 N-linked glycans 117:132 N-glycanase 1(NGLY1) catalyzes the removal of N-linked glycans from newly synthesized or misfolded protein. 36209585 7 4 theme several 825:831 arg1 candidates 837:846 several key candidates 825:846 several key candidates that were subjected to isobarically labeled proteomic analysis 825:909 Further biological validation assays confirmed the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis. 36209585 8 5 theme further 934:940 arg1 analysis 942:949 further analysis 934:949 further analysis due to its significant increase in different cell models of NGLY1 deficiency 934:1026 CCN2 was selected for further analysis due to its significant increase in different cell models of NGLY1 deficiency. 36209585 10 6 from link 1234:1237 arg1 patients 1316:1323 NGLY1 patients 1310:1323 NGLY1 patients 1310:1323 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 6 7 from levels 681:686 arg1 cells 746:750 NGLY1-defective human and mouse cells 714:750 NGLY1-defective human and mouse cells 714:750 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 6 8 theme proteins 702:709 arg1 levels 681:686 elevated levels 672:686 elevated levels of endogenous proteins in NGLY1-defective human and mouse cells 672:750 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 7 9 theme key 833:835 arg1 candidates 837:846 several key candidates 825:846 several key candidates that were subjected to isobarically labeled proteomic analysis 825:909 Further biological validation assays confirmed the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis. 36209585 9 10 theme elevated 1052:1059 arg1 CCN2 1061:1064 elevated CCN2 1052:1064 elevated CCN2 1052:1064 Functional assays show elevated CCN2 and over-stimulated TGF-β signaling in NGLY1-deficient cells. 36209585 6 11 theme elevated 672:679 arg1 levels 681:686 elevated levels 672:686 elevated levels of endogenous proteins in NGLY1-defective human and mouse cells 672:750 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 6 12 from cells 746:750 arg1 levels 681:686 elevated levels 672:686 elevated levels of endogenous proteins in NGLY1-defective human and mouse cells 672:750 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 6 13 theme endogenous 691:700 arg1 proteins 702:709 endogenous proteins 691:709 endogenous proteins in NGLY1-defective human and mouse cells 691:750 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 10 14 theme CCN2 1156:1159 arg1 pathway 1171:1177 CCN2 and TGF-β pathway 1156:1177 CCN2 and TGF-β pathway 1156:1177 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 10 15 theme potential 1224:1232 arg1 link 1234:1237 a potential link 1222:1237 a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients 1222:1323 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 10 16 theme pathway 1171:1177 arg1 role 1148:1151 the important role 1134:1151 the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis 1134:1208 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 4 17 theme mitochondrial 432:444 arg1 homeostasis 446:456 mitochondrial homeostasis 432:456 mitochondrial homeostasis 432:456 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 9 18 from CCN2 1061:1064 arg1 cells 1121:1125 NGLY1-deficient cells 1105:1125 NGLY1-deficient cells 1105:1125 Functional assays show elevated CCN2 and over-stimulated TGF-β signaling in NGLY1-deficient cells. 36209585 8 19 theme different 986:994 arg1 models 1001:1006 different cell models 986:1006 different cell models of NGLY1 deficiency 986:1026 CCN2 was selected for further analysis due to its significant increase in different cell models of NGLY1 deficiency. 36209585 3 20 theme affected 247:254 arg1 individuals 256:266 The affected individuals 243:266 The affected individuals 243:266 The affected individuals present a broad spectrum of clinical features. 36209585 1 21 theme misfolded 160:168 arg1 protein 170:176 newly synthesized or misfolded protein 139:176 newly synthesized or misfolded protein 139:176 N-glycanase 1(NGLY1) catalyzes the removal of N-linked glycans from newly synthesized or misfolded protein. 36209585 9 22 theme over-stimulated 1070:1084 arg1 signaling 1092:1100 over-stimulated TGF-β signaling 1070:1100 over-stimulated TGF-β signaling 1070:1100 Functional assays show elevated CCN2 and over-stimulated TGF-β signaling in NGLY1-deficient cells. 36209585 4 23 theme deficiency 386:395 arg1 defects 407:413 defects 407:413 defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport 407:498 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 4 23 theme deficiency 386:395 arg1 mechanisms 366:375 several possible molecular mechanisms 339:375 several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport 339:498 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 5 24 theme endoplasmic 541:551 arg1 ERAD 587:590 ERAD 587:590 ERAD 587:590 We demonstrate abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells. 36209585 5 24 theme endoplasmic 541:551 arg1 degradation 574:584 endoplasmic reticulum-associated degradation 541:584 endoplasmic reticulum-associated degradation (ERAD) substrates 541:602 We demonstrate abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells. 36209585 9 25 theme TGF-β 1086:1090 arg1 signaling 1092:1100 over-stimulated TGF-β signaling 1070:1100 over-stimulated TGF-β signaling 1070:1100 Functional assays show elevated CCN2 and over-stimulated TGF-β signaling in NGLY1-deficient cells. 36209585 0 26 from CCN2 40:43 arg1 cells 64:68 NGLY1-deficient cells 48:68 NGLY1-deficient cells 48:68 Comparative proteomics reveals elevated CCN2 in NGLY1-deficient cells. 36209585 8 27 theme significant 962:972 arg1 increase 974:981 its significant increase 958:981 its significant increase in different cell models of NGLY1 deficiency 958:1026 CCN2 was selected for further analysis due to its significant increase in different cell models of NGLY1 deficiency. 36209585 4 28 theme NGLY1 380:384 arg1 deficiency 386:395 NGLY1 deficiency 380:395 NGLY1 deficiency 380:395 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 4 29 from defects 407:413 arg1 proteostasis 418:429 proteostasis 418:429 proteostasis 418:429 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 4 29 from defects 407:413 arg1 homeostasis 446:456 mitochondrial homeostasis 432:456 mitochondrial homeostasis 432:456 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 4 29 from defects 407:413 arg1 immunity 466:473 innate immunity 459:473 innate immunity 459:473 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 4 29 from defects 407:413 arg1 transport 490:498 water/ion transport 480:498 water/ion transport 480:498 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 5 30 theme reticulum-associated 553:572 arg1 ERAD 587:590 ERAD 587:590 ERAD 587:590 We demonstrate abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells. 36209585 5 30 theme reticulum-associated 553:572 arg1 degradation 574:584 endoplasmic reticulum-associated degradation 541:584 endoplasmic reticulum-associated degradation (ERAD) substrates 541:602 We demonstrate abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells. 36209585 0 31 theme Comparative 0:10 arg1 proteomics 12:21 Comparative proteomics 0:21 Comparative proteomics 0:21 Comparative proteomics reveals elevated CCN2 in NGLY1-deficient cells. 36209585 10 32 theme CCN2 1252:1255 arg1 signaling 1267:1275 increased CCN2 and TGF-β signaling 1242:1275 increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients 1242:1323 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 7 33 theme Further 753:759 arg1 assays 783:788 Further biological validation assays 753:788 Further biological validation assays 753:788 Further biological validation assays confirmed the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis. 36209585 10 34 from signaling 1267:1275 arg1 patients 1316:1323 NGLY1 patients 1310:1323 NGLY1 patients 1310:1323 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 0 35 theme elevated 31:38 arg1 CCN2 40:43 elevated CCN2 31:43 elevated CCN2 in NGLY1-deficient cells 31:68 Comparative proteomics reveals elevated CCN2 in NGLY1-deficient cells. 36209585 10 36 theme increased 1242:1250 arg1 signaling 1267:1275 increased CCN2 and TGF-β signaling 1242:1275 increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients 1242:1323 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 3 37 theme broad 278:282 arg1 spectrum 284:291 a broad spectrum 276:291 a broad spectrum of clinical features 276:312 The affected individuals present a broad spectrum of clinical features. 36209585 8 38 from increase 974:981 arg1 models 1001:1006 different cell models 986:1006 different cell models of NGLY1 deficiency 986:1026 CCN2 was selected for further analysis due to its significant increase in different cell models of NGLY1 deficiency. 36209585 10 39 from patients 1316:1323 arg1 link 1234:1237 a potential link 1222:1237 a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients 1222:1323 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 10 40 theme liver 1292:1296 arg1 fibrosis 1298:1305 microscopic liver fibrosis 1280:1305 microscopic liver fibrosis 1280:1305 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 9 41 theme NGLY1-deficient 1105:1119 arg1 cells 1121:1125 NGLY1-deficient cells 1105:1125 NGLY1-deficient cells 1105:1125 Functional assays show elevated CCN2 and over-stimulated TGF-β signaling in NGLY1-deficient cells. 36209585 10 42 theme NGLY1 1310:1314 arg1 patients 1316:1323 NGLY1 patients 1310:1323 NGLY1 patients 1310:1323 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 9 43 from signaling 1092:1100 arg1 cells 1121:1125 NGLY1-deficient cells 1105:1125 NGLY1-deficient cells 1105:1125 Functional assays show elevated CCN2 and over-stimulated TGF-β signaling in NGLY1-deficient cells. 36209585 2 44 theme NGLY1 179:183 arg1 disorder 233:240 a recently diagnosed rare genetic disorder 199:240 a recently diagnosed rare genetic disorder 199:240 NGLY1 deficiency is a recently diagnosed rare genetic disorder. 36209585 2 44 theme NGLY1 179:183 arg1 deficiency 185:194 NGLY1 deficiency 179:194 NGLY1 deficiency 179:194 NGLY1 deficiency is a recently diagnosed rare genetic disorder. 36209585 8 45 theme NGLY1 1011:1015 arg1 deficiency 1017:1026 NGLY1 deficiency 1011:1026 NGLY1 deficiency 1011:1026 CCN2 was selected for further analysis due to its significant increase in different cell models of NGLY1 deficiency. 36209585 8 46 theme deficiency 1017:1026 arg1 models 1001:1006 different cell models 986:1006 different cell models of NGLY1 deficiency 986:1026 CCN2 was selected for further analysis due to its significant increase in different cell models of NGLY1 deficiency. 36209585 7 47 theme altered 804:810 arg1 abundance 812:820 the altered abundance 800:820 the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis 800:909 Further biological validation assays confirmed the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis. 36209585 5 48 theme abnormal 516:523 arg1 accumulation 525:536 abnormal accumulation 516:536 abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells 516:627 We demonstrate abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells. 36209585 6 49 theme quantitative 637:648 arg1 proteomics 650:659 Global quantitative proteomics 630:659 Global quantitative proteomics 630:659 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 7 50 theme labeled 884:890 arg1 analysis 902:909 isobarically labeled proteomic analysis 871:909 isobarically labeled proteomic analysis 871:909 Further biological validation assays confirmed the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis. 36209585 2 51 theme genetic 225:231 arg1 disorder 233:240 a recently diagnosed rare genetic disorder 199:240 a recently diagnosed rare genetic disorder 199:240 NGLY1 deficiency is a recently diagnosed rare genetic disorder. 36209585 2 51 theme genetic 225:231 arg1 deficiency 185:194 NGLY1 deficiency 179:194 NGLY1 deficiency 179:194 NGLY1 deficiency is a recently diagnosed rare genetic disorder. 36209585 4 52 theme molecular 356:364 arg1 defects 407:413 defects 407:413 defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport 407:498 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 4 52 theme molecular 356:364 arg1 mechanisms 366:375 several possible molecular mechanisms 339:375 several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport 339:498 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 6 53 theme Global 630:635 arg1 proteomics 650:659 Global quantitative proteomics 630:659 Global quantitative proteomics 630:659 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 7 54 theme proteomic 892:900 arg1 analysis 902:909 isobarically labeled proteomic analysis 871:909 isobarically labeled proteomic analysis 871:909 Further biological validation assays confirmed the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis. 36209585 3 55 theme features 305:312 arg1 spectrum 284:291 a broad spectrum 276:291 a broad spectrum of clinical features 276:312 The affected individuals present a broad spectrum of clinical features. 36209585 4 56 theme water/ion 480:488 arg1 transport 490:498 water/ion transport 480:498 water/ion transport 480:498 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 2 57 theme rare 220:223 arg1 disorder 233:240 a recently diagnosed rare genetic disorder 199:240 a recently diagnosed rare genetic disorder 199:240 NGLY1 deficiency is a recently diagnosed rare genetic disorder. 36209585 2 57 theme rare 220:223 arg1 deficiency 185:194 NGLY1 deficiency 179:194 NGLY1 deficiency 179:194 NGLY1 deficiency is a recently diagnosed rare genetic disorder. 36209585 4 58 theme possible 347:354 arg1 defects 407:413 defects 407:413 defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport 407:498 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 4 58 theme possible 347:354 arg1 mechanisms 366:375 several possible molecular mechanisms 339:375 several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport 339:498 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 0 59 theme NGLY1-deficient 48:62 arg1 cells 64:68 NGLY1-deficient cells 48:68 NGLY1-deficient cells 48:68 Comparative proteomics reveals elevated CCN2 in NGLY1-deficient cells. 36209585 10 60 theme TGF-β 1261:1265 arg1 signaling 1267:1275 increased CCN2 and TGF-β signaling 1242:1275 increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients 1242:1323 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 7 61 theme biological 761:770 arg1 assays 783:788 Further biological validation assays 753:788 Further biological validation assays 753:788 Further biological validation assays confirmed the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis. 36209585 2 62 theme diagnosed 210:218 arg1 disorder 233:240 a recently diagnosed rare genetic disorder 199:240 a recently diagnosed rare genetic disorder 199:240 NGLY1 deficiency is a recently diagnosed rare genetic disorder. 36209585 2 62 theme diagnosed 210:218 arg1 deficiency 185:194 NGLY1 deficiency 179:194 NGLY1 deficiency 179:194 NGLY1 deficiency is a recently diagnosed rare genetic disorder. 36209585 5 63 theme NGLY1-deficient 607:621 arg1 cells 623:627 NGLY1-deficient cells 607:627 NGLY1-deficient cells 607:627 We demonstrate abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells. 36209585 10 64 theme important 1138:1146 arg1 role 1148:1151 the important role 1134:1151 the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis 1134:1208 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 7 65 theme validation 772:781 arg1 assays 783:788 Further biological validation assays 753:788 Further biological validation assays 753:788 Further biological validation assays confirmed the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis. 36209585 6 66 from proteins 702:709 arg1 cells 746:750 NGLY1-defective human and mouse cells 714:750 NGLY1-defective human and mouse cells 714:750 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 1 67 theme N-linked 117:124 arg1 glycans 126:132 N-linked glycans 117:132 N-linked glycans 117:132 N-glycanase 1(NGLY1) catalyzes the removal of N-linked glycans from newly synthesized or misfolded protein. 36209585 6 68 theme mouse 740:744 arg1 cells 746:750 NGLY1-defective human and mouse cells 714:750 NGLY1-defective human and mouse cells 714:750 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 3 69 theme clinical 296:303 arg1 features 305:312 clinical features 296:312 clinical features 296:312 The affected individuals present a broad spectrum of clinical features. 36209585 10 70 theme TGF-β 1165:1169 arg1 pathway 1171:1177 CCN2 and TGF-β pathway 1156:1177 CCN2 and TGF-β pathway 1156:1177 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 5 71 theme substrates 593:602 arg1 accumulation 525:536 abnormal accumulation 516:536 abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells 516:627 We demonstrate abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells. 36209585 5 72 theme degradation 574:584 arg1 substrates 593:602 endoplasmic reticulum-associated degradation (ERAD) substrates 541:602 endoplasmic reticulum-associated degradation (ERAD) substrates 541:602 We demonstrate abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells. 36209585 1 73 theme glycans 126:132 arg1 removal 106:112 the removal 102:112 the removal of N-linked glycans from newly synthesized or misfolded protein 102:176 N-glycanase 1(NGLY1) catalyzes the removal of N-linked glycans from newly synthesized or misfolded protein. 36209585 8 74 theme cell 996:999 arg1 models 1001:1006 different cell models 986:1006 different cell models of NGLY1 deficiency 986:1026 CCN2 was selected for further analysis due to its significant increase in different cell models of NGLY1 deficiency. 36209585 4 75 theme innate 459:464 arg1 immunity 466:473 innate immunity 459:473 innate immunity 459:473 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 5 76 from accumulation 525:536 arg1 cells 623:627 NGLY1-deficient cells 607:627 NGLY1-deficient cells 607:627 We demonstrate abnormal accumulation of endoplasmic reticulum-associated degradation (ERAD) substrates in NGLY1-deficient cells. 36209585 4 77 theme Recent 315:320 arg1 studies 322:328 Recent studies 315:328 Recent studies 315:328 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 6 78 theme human 730:734 arg1 cells 746:750 NGLY1-defective human and mouse cells 714:750 NGLY1-defective human and mouse cells 714:750 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 7 79 theme candidates 837:846 arg1 abundance 812:820 the altered abundance 800:820 the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis 800:909 Further biological validation assays confirmed the altered abundance of several key candidates that were subjected to isobarically labeled proteomic analysis. 36209585 9 80 theme Functional 1029:1038 arg1 assays 1040:1045 Functional assays 1029:1045 Functional assays 1029:1045 Functional assays show elevated CCN2 and over-stimulated TGF-β signaling in NGLY1-deficient cells. 36209585 10 81 theme microscopic 1280:1290 arg1 fibrosis 1298:1305 microscopic liver fibrosis 1280:1305 microscopic liver fibrosis 1280:1305 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36209585 4 82 theme several 339:345 arg1 defects 407:413 defects 407:413 defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport 407:498 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 4 82 theme several 339:345 arg1 mechanisms 366:375 several possible molecular mechanisms 339:375 several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport 339:498 Recent studies explored several possible molecular mechanisms of NGLY1 deficiency including defects in proteostasis, mitochondrial homeostasis, innate immunity, and water/ion transport. 36209585 6 83 theme NGLY1-defective 714:728 arg1 cells 746:750 NGLY1-defective human and mouse cells 714:750 NGLY1-defective human and mouse cells 714:750 Global quantitative proteomics discovered elevated levels of endogenous proteins in NGLY1-defective human and mouse cells. 36209585 10 84 theme signaling 1267:1275 arg1 link 1234:1237 a potential link 1222:1237 a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients 1222:1323 Given the important role of CCN2 and TGF-β pathway in mediating systemic fibrosis, we propose a potential link of increased CCN2 and TGF-β signaling to microscopic liver fibrosis in NGLY1 patients. 36475339 6 0 theme enrichment 1007:1016 arg1 analysis 1018:1025 gene set enrichment analysis 998:1025 gene set enrichment analysis (GSEA) 998:1032 Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). 36475339 6 0 theme enrichment 1007:1016 arg1 GSEA 1028:1031 GSEA 1028:1031 GSEA 1028:1031 Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). 36475339 7 1 theme Immune 1035:1040 arg1 infiltrates 1042:1052 Immune infiltrates 1035:1052 Immune infiltrates correlation of BIN3 in ESCA 1035:1080 Immune infiltrates correlation of BIN3 in ESCA was performed by TIMER and ssGSEA. 36475339 2 2 theme clinical 281:288 arg1 value 290:294 clinical value 281:294 clinical value 281:294 Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). 36475339 1 3 theme key 204:206 arg1 role 208:211 a key role 202:211 a key role 202:211 BACKGROUND Bridging integrator 3 (BIN3) has been reported to play a key role in certain tumors. 36475339 15 4 theme cells 2449:2453 arg1 level 2376:2380 the infiltration level 2359:2380 the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001) 2359:2496 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 15 5 theme cells 2387:2391 arg1 level 2376:2380 the infiltration level 2359:2380 the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001) 2359:2496 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 11 6 theme T 1695:1695 arg1 stage 1697:1701 T stage 1695:1701 T stage (p < 0.05) 1695:1712 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 11 6 theme T 1695:1695 arg1 < 1706:1706 p < 0.05 1704:1711 p < 0.05 1704:1711 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 12 7 theme BIN3 1808:1811 arg1 expression 1813:1822 high BIN3 expression 1803:1822 high BIN3 expression 1803:1822 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 8 8 from influence 1121:1129 arg1 EMT 1177:1179 EMT 1177:1179 EMT 1177:1179 The influence of BIN3 on epithelial-mesenchymal transition (EMT) was validated by western blot. 36475339 8 8 from influence 1121:1129 arg1 transition 1165:1174 epithelial-mesenchymal transition 1142:1174 epithelial-mesenchymal transition (EMT) 1142:1180 The influence of BIN3 on epithelial-mesenchymal transition (EMT) was validated by western blot. 36475339 18 9 theme ESCA 2835:2838 arg1 infiltration 2819:2830 the immune infiltration 2808:2830 the immune infiltration of ESCA 2808:2838 BIN3 functions as a tumor-suppressor role in ESCA, which is significantly associated with the immune infiltration of ESCA. 36475339 2 10 from role 272:275 arg1 carcinoma 317:325 esophagus carcinoma 307:325 esophagus carcinoma (ESCA) 307:332 Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). 36475339 2 10 from role 272:275 arg1 ESCA 328:331 ESCA 328:331 ESCA 328:331 Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). 36475339 15 11 theme cells 2427:2431 arg1 level 2376:2380 the infiltration level 2359:2380 the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001) 2359:2496 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 3 12 from role 399:402 arg1 patients 420:427 ESCA patients 415:427 ESCA patients 415:427 This study aimed to investigate the pathological and prognostic role of BIN3 in ESCA patients. 36475339 5 13 theme BIN3 728:731 arg1 expression 714:723 The expression 710:723 The expression of BIN3, pathological features correlation and subgroup overall survival analysis 710:805 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 5 14 theme survival 789:796 arg1 analysis 798:805 subgroup overall survival analysis 772:805 subgroup overall survival analysis 772:805 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 16 15 theme E-cadherin 2577:2586 arg1 expression 2588:2597 E-cadherin expression 2577:2597 E-cadherin expression in ESCA cell lines TE-1 2577:2621 In addition, BIN3 overexpression inhibited N-cadherin expression and promoted E-cadherin expression in ESCA cell lines TE-1. 36475339 17 16 theme prognostic 2688:2697 arg1 BIN3 2662:2665 BIN3 2662:2665 BIN3 2662:2665 CONCLUSION These results suggest that BIN3 might be a potential prognostic biomarker in ESCA. 36475339 17 16 theme prognostic 2688:2697 arg1 biomarker 2699:2707 a potential prognostic biomarker 2676:2707 a potential prognostic biomarker in ESCA 2676:2715 CONCLUSION These results suggest that BIN3 might be a potential prognostic biomarker in ESCA. 36475339 15 17 theme infiltration 2363:2374 arg1 level 2376:2380 the infiltration level 2359:2380 the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001) 2359:2496 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 14 18 theme beta 2252:2255 arg1 development 2262:2272 beta cell development 2252:2272 beta cell development 2252:2272 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 15 19 theme < 2415:2415 arg1 p 2413:2413 p < 0.001 2413:2421 p < 0.001 2413:2421 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 15 19 theme < 2415:2415 arg1 Tregs 2406:2410 Tregs 2406:2410 Tregs (p < 0.001) 2406:2422 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 11 20 theme p 1773:1773 arg1 gender 1765:1770 gender 1765:1770 gender (p < 0.05) 1765:1781 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 11 20 theme p 1773:1773 arg1 < 1775:1775 p < 0.05 1773:1780 p < 0.05 1773:1780 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 5 21 theme correlation 756:766 arg1 expression 714:723 The expression 710:723 The expression of BIN3, pathological features correlation and subgroup overall survival analysis 710:805 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 18 22 theme tumor-suppressor 2738:2753 arg1 role 2755:2758 a tumor-suppressor role 2736:2758 a tumor-suppressor role 2736:2758 BIN3 functions as a tumor-suppressor role in ESCA, which is significantly associated with the immune infiltration of ESCA. 36475339 18 22 theme tumor-suppressor 2738:2753 arg1 BIN3 2718:2721 BIN3 2718:2721 BIN3 2718:2721 BIN3 functions as a tumor-suppressor role in ESCA, which is significantly associated with the immune infiltration of ESCA. 36475339 0 23 from Prognosis 60:68 arg1 Patients 73:80 Patients 73:80 Patients with Esophagus Carcinoma: A Study based on TCGA Data 73:133 Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data. 36475339 15 24 theme M2 2483:2484 arg1 level 2376:2380 the infiltration level 2359:2380 the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001) 2359:2496 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 4 25 theme genes 588:592 arg1 analysis 551:558 comprehensive analysis 537:558 comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) 537:699 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 5 26 theme subgroup 772:779 arg1 analysis 798:805 subgroup overall survival analysis 772:805 subgroup overall survival analysis 772:805 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 12 27 theme OS 1977:1978 arg1 gender 1891:1896 gender 1891:1896 gender (male) 1891:1903 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 27 theme OS 1977:1978 arg1 stage 1862:1866 T stage 1860:1866 T stage (T3 & T4) 1860:1876 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 27 theme OS 1977:1978 arg1 outcome 1922:1928 primary therapy outcome 1906:1928 primary therapy outcome (PD) 1906:1933 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 27 theme OS 1977:1978 arg1 metaplasia 1948:1957 columnar metaplasia 1939:1957 columnar metaplasia (No) of favorable OS 1939:1978 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 27 theme OS 1977:1978 arg1 age 1879:1881 age (＜＝60) 1879:1888 age (＜＝60) 1879:1888 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 27 theme OS 1977:1978 arg1 No 1960:1961 No 1960:1961 No 1960:1961 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 27 theme OS 1977:1978 arg1 male 1899:1902 male 1899:1902 male 1899:1902 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 27 theme OS 1977:1978 arg1 PD 1931:1932 PD 1931:1932 PD 1931:1932 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 27 theme OS 1977:1978 arg1 T4 1874:1875 T3 & T4 1869:1875 T3 & T4 1869:1875 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 14 28 theme development 2262:2272 arg1 pathway 2166:2172 PID HNF3B pathway 2156:2172 PID HNF3B pathway 2156:2172 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 28 theme development 2262:2272 arg1 others 2317:2322 others 2317:2322 others 2317:2322 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 28 theme development 2262:2272 arg1 regulation 2238:2247 reactome regulation 2229:2247 reactome regulation of beta cell development 2229:2272 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 28 theme development 2262:2272 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 28 theme development 2262:2272 arg1 cycle 2283:2287 WP Urea cycle 2275:2287 WP Urea cycle 2275:2287 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 28 theme development 2262:2272 arg1 pathway 2188:2194 biocarta TFF pathway 2175:2194 biocarta TFF pathway 2175:2194 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 28 theme development 2262:2272 arg1 pathway 2220:2226 WP pregnane X receptor pathway 2197:2226 WP pregnane X receptor pathway 2197:2226 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 28 theme development 2262:2272 arg1 pathways 2304:2311 pathways 2304:2311 pathways 2304:2311 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 12 29 theme high 1803:1806 arg1 expression 1813:1822 high BIN3 expression 1803:1822 high BIN3 expression 1803:1822 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 10 30 theme mRNA 1490:1493 arg1 level 1495:1499 The BIN3 mRNA level 1481:1499 The BIN3 mRNA level 1481:1499 The BIN3 mRNA level was found to be significantly decreased in ESCA compared to normal tissues (p < 0.05). 36475339 11 31 theme clinical 1667:1674 arg1 stage 1676:1680 the clinical stage 1663:1680 the clinical stage (p = 0.015) 1663:1692 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 11 31 theme clinical 1667:1674 arg1 0.015 1687:1691 p = 0.015 1683:1691 p = 0.015 1683:1691 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 14 32 theme receptor 2211:2218 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 32 theme receptor 2211:2218 arg1 pathway 2220:2226 WP pregnane X receptor pathway 2197:2226 WP pregnane X receptor pathway 2197:2226 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 16 33 from expression 2588:2597 arg1 lines 2612:2616 ESCA cell lines TE-1 2602:2621 ESCA cell lines TE-1 2602:2621 In addition, BIN3 overexpression inhibited N-cadherin expression and promoted E-cadherin expression in ESCA cell lines TE-1. 36475339 14 34 link linked 2124:2129 arg1 glycosylation 2131:2143 O linked glycosylation 2122:2143 O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others 2122:2322 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 15 35 theme < 2489:2489 arg1 M2 2483:2484 macrophage M2 2472:2484 macrophage M2 (p < 0.001) 2472:2496 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 15 35 theme < 2489:2489 arg1 p 2487:2487 p < 0.001 2487:2495 p < 0.001 2487:2495 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 9 36 theme diseasespecific 1396:1410 arg1 DSS 1422:1424 DSS 1422:1424 DSS 1422:1424 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 9 36 theme diseasespecific 1396:1410 arg1 survival 1412:1419 diseasespecific survival 1396:1419 diseasespecific survival (DSS) 1396:1425 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 14 37 theme pregnane 2200:2207 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 37 theme pregnane 2200:2207 arg1 pathway 2220:2226 WP pregnane X receptor pathway 2197:2226 WP pregnane X receptor pathway 2197:2226 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 9 38 from interval 1448:1455 arg1 patients 1471:1478 ESCA patients 1466:1478 ESCA patients 1466:1478 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 7 39 from correlation 1054:1064 arg1 ESCA 1077:1080 ESCA 1077:1080 ESCA 1077:1080 Immune infiltrates correlation of BIN3 in ESCA was performed by TIMER and ssGSEA. 36475339 5 40 theme Cancer 832:837 arg1 Atlas 846:850 The Cancer Genome Atlas 828:850 The Cancer Genome Atlas (TCGA) 828:857 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 5 40 theme Cancer 832:837 arg1 TCGA 853:856 TCGA 853:856 TCGA 853:856 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 14 41 theme TFF 2184:2186 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 41 theme TFF 2184:2186 arg1 pathway 2188:2194 biocarta TFF pathway 2175:2194 biocarta TFF pathway 2175:2194 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 2 42 dep role 272:275 arg1 the 268:270 the 268:270 the 268:270 Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). 36475339 11 43 theme BIN3 1616:1619 arg1 expression 1602:1611 The decreased expression 1588:1611 The decreased expression of BIN3 in ESCA 1588:1627 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 9 44 theme progression-free 1431:1446 arg1 interval 1448:1455 progression-free interval 1431:1455 progression-free interval (PFI) 1431:1461 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 9 44 theme progression-free 1431:1446 arg1 PFI 1458:1460 PFI 1458:1460 PFI 1458:1460 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 6 45 theme potential 893:901 arg1 pathways 913:920 the potential signaling pathways 889:920 the potential signaling pathways in which BIN3 was involved 889:947 Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). 36475339 12 46 theme primary 1906:1912 arg1 outcome 1922:1928 primary therapy outcome 1906:1928 primary therapy outcome (PD) 1906:1933 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 46 theme primary 1906:1912 arg1 PD 1931:1932 PD 1931:1932 PD 1931:1932 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 11 47 theme p 1734:1734 arg1 type 1728:1731 histological type 1715:1731 histological type (p < 0.001) 1715:1743 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 11 47 theme p 1734:1734 arg1 < 1736:1736 p < 0.001 1734:1742 p < 0.001 1734:1742 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 0 48 theme Esophagus 87:95 arg1 Carcinoma 97:105 Esophagus Carcinoma 87:105 Esophagus Carcinoma 87:105 Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data. 36475339 0 49 dep Patients 73:80 arg1 Study 110:114 A Study 108:114 Patients with Esophagus Carcinoma: A Study based on TCGA Data 73:133 Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data. 36475339 2 50 theme esophagus 307:315 arg1 carcinoma 317:325 esophagus carcinoma 307:325 esophagus carcinoma (ESCA) 307:332 Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). 36475339 2 50 theme esophagus 307:315 arg1 ESCA 328:331 ESCA 328:331 ESCA 328:331 Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). 36475339 0 51 theme Bridging 0:7 arg1 Downregulation 29:42 Integrator 3 (BIN3) Downregulation 9:42 Bridging Integrator 3 (BIN3) Downregulation 0:42 Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data. 36475339 1 52 theme certain 216:222 arg1 tumors 224:229 certain tumors 216:229 certain tumors 216:229 BACKGROUND Bridging integrator 3 (BIN3) has been reported to play a key role in certain tumors. 36475339 6 53 theme enrichment 974:983 arg1 analysis 985:992 GO-KEGG enrichment analysis 966:992 GO-KEGG enrichment analysis 966:992 Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). 36475339 5 54 theme pathological 734:745 arg1 features 747:754 pathological features 734:754 pathological features correlation 734:766 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 9 55 theme expressed 1251:1259 arg1 genes 1261:1265 two differentially expressed genes 1232:1265 two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients 1232:1478 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 9 56 theme ESCA 1466:1469 arg1 patients 1471:1478 ESCA patients 1466:1478 ESCA patients 1466:1478 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 18 57 theme immune 2812:2817 arg1 infiltration 2819:2830 the immune infiltration 2808:2830 the immune infiltration of ESCA 2808:2838 BIN3 functions as a tumor-suppressor role in ESCA, which is significantly associated with the immune infiltration of ESCA. 36475339 11 58 theme histological 1715:1726 arg1 type 1728:1731 histological type 1715:1731 histological type (p < 0.001) 1715:1743 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 11 58 theme histological 1715:1726 arg1 < 1736:1736 p < 0.001 1734:1742 p < 0.001 1734:1742 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 7 59 theme BIN3 1069:1072 arg1 correlation 1054:1064 Immune infiltrates correlation 1035:1064 Immune infiltrates correlation of BIN3 in ESCA 1035:1080 Immune infiltrates correlation of BIN3 in ESCA was performed by TIMER and ssGSEA. 36475339 9 60 theme related 1267:1273 arg1 genes 1261:1265 two differentially expressed genes 1232:1265 two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients 1232:1478 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 0 61 theme BIN3 23:26 arg1 Downregulation 29:42 Integrator 3 (BIN3) Downregulation 9:42 Bridging Integrator 3 (BIN3) Downregulation 0:42 Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data. 36475339 14 62 theme PID 2156:2158 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 62 theme PID 2156:2158 arg1 pathway 2166:2172 PID HNF3B pathway 2156:2172 PID HNF3B pathway 2156:2172 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 9 63 from survival 1381:1388 arg1 patients 1471:1478 ESCA patients 1466:1478 ESCA patients 1466:1478 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 14 64 theme several 2074:2080 arg1 pathways 2082:2089 several pathways 2074:2089 several pathways 2074:2089 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 10 65 theme p 1577:1577 arg1 tissues 1568:1574 normal tissues 1561:1574 normal tissues (p < 0.05) 1561:1585 The BIN3 mRNA level was found to be significantly decreased in ESCA compared to normal tissues (p < 0.05). 36475339 10 65 theme p 1577:1577 arg1 < 1579:1579 p < 0.05 1577:1584 p < 0.05 1577:1584 The BIN3 mRNA level was found to be significantly decreased in ESCA compared to normal tissues (p < 0.05). 36475339 14 66 theme mucins 2148:2153 arg1 glycosylation 2131:2143 O linked glycosylation 2122:2143 O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others 2122:2322 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 67 theme associated 2293:2302 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 67 theme associated 2293:2302 arg1 pathways 2304:2311 pathways 2304:2311 pathways 2304:2311 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 9 68 dep RESULTS 1213:1219 arg1 were 1227:1230 were 1227:1230 were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients 1227:1478 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 12 69 with patients 1789:1796 arg1 expression 1813:1822 high BIN3 expression 1803:1822 high BIN3 expression 1803:1822 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 70 theme T3 1869:1870 arg1 T4 1874:1875 T3 & T4 1869:1875 T3 & T4 1869:1875 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 70 theme T3 1869:1870 arg1 stage 1862:1866 T stage 1860:1866 T stage (T3 & T4) 1860:1876 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 11 71 theme = 1685:1685 arg1 stage 1676:1680 the clinical stage 1663:1680 the clinical stage (p = 0.015) 1663:1692 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 11 71 theme = 1685:1685 arg1 0.015 1687:1691 p = 0.015 1683:1691 p = 0.015 1683:1691 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 13 72 theme enrichment 1989:1998 arg1 analysis 2000:2007 GO-KEGG enrichment analysis 1981:2007 GO-KEGG enrichment analysis 1981:2007 GO-KEGG enrichment analysis revealed that BIN3 was involved in endocytosis. 36475339 2 73 theme BIN3 299:302 arg1 role 272:275 role 272:275 role 272:275 Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). 36475339 2 73 theme BIN3 299:302 arg1 value 290:294 clinical value 281:294 clinical value 281:294 Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). 36475339 9 74 theme gene 1343:1346 arg1 clusters 1348:1355 three gene clusters 1337:1355 three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients 1337:1478 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 9 75 theme patients 1300:1307 arg1 prognosis 1282:1290 the prognosis 1278:1290 the prognosis 1278:1290 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 18 76 from role 2755:2758 arg1 ESCA 2763:2766 ESCA 2763:2766 ESCA 2763:2766 BIN3 functions as a tumor-suppressor role in ESCA, which is significantly associated with the immune infiltration of ESCA. 36475339 14 77 theme WP 2275:2276 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 77 theme WP 2275:2276 arg1 cycle 2283:2287 WP Urea cycle 2275:2287 WP Urea cycle 2275:2287 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 4 78 theme comprehensive 537:549 arg1 analysis 551:558 comprehensive analysis 537:558 comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) 537:699 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 3 79 theme ESCA 415:418 arg1 patients 420:427 ESCA patients 415:427 ESCA patients 415:427 This study aimed to investigate the pathological and prognostic role of BIN3 in ESCA patients. 36475339 17 80 dep CONCLUSION 2624:2633 arg1 suggest 2649:2655 suggest 2649:2655 suggest that BIN3 might be a potential prognostic biomarker in ESCA 2649:2715 CONCLUSION These results suggest that BIN3 might be a potential prognostic biomarker in ESCA. 36475339 6 81 theme set 1003:1005 arg1 analysis 1018:1025 gene set enrichment analysis 998:1025 gene set enrichment analysis (GSEA) 998:1032 Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). 36475339 6 81 theme set 1003:1005 arg1 GSEA 1028:1031 GSEA 1028:1031 GSEA 1028:1031 Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). 36475339 4 82 theme patients 496:503 arg1 prognosis 478:486 the prognosis 474:486 the prognosis of ESCA patients 474:503 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 15 83 theme T 2385:2385 arg1 cells 2387:2391 T cells 2385:2391 T cells (p < 0.001) 2385:2403 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 15 83 theme T 2385:2385 arg1 p 2394:2394 p < 0.001 2394:2402 p < 0.001 2394:2402 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 9 84 from survival 1412:1419 arg1 patients 1471:1478 ESCA patients 1466:1478 ESCA patients 1466:1478 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 15 85 theme < 2436:2436 arg1 p 2434:2434 p < 0.001 2434:2442 p < 0.001 2434:2442 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 15 85 theme < 2436:2436 arg1 cells 2427:2431 B cells 2425:2431 B cells (p < 0.001) 2425:2443 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 3 86 theme BIN3 407:410 arg1 role 399:402 the pathological and prognostic role 367:402 the pathological and prognostic role of BIN3 in ESCA patients 367:427 This study aimed to investigate the pathological and prognostic role of BIN3 in ESCA patients. 36475339 14 87 gly glycosylation 2131:2143 arg1 pathway 2166:2172 PID HNF3B pathway 2156:2172 PID HNF3B pathway 2156:2172 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 87 gly glycosylation 2131:2143 arg1 regulation 2238:2247 reactome regulation 2229:2247 reactome regulation of beta cell development 2229:2272 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 87 gly glycosylation 2131:2143 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 87 gly glycosylation 2131:2143 arg1 cycle 2283:2287 WP Urea cycle 2275:2287 WP Urea cycle 2275:2287 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 87 gly glycosylation 2131:2143 arg1 pathway 2188:2194 biocarta TFF pathway 2175:2194 biocarta TFF pathway 2175:2194 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 87 gly glycosylation 2131:2143 arg1 pathway 2220:2226 WP pregnane X receptor pathway 2197:2226 WP pregnane X receptor pathway 2197:2226 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 87 gly glycosylation 2131:2143 arg1 pathways 2304:2311 pathways 2304:2311 pathways 2304:2311 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 5 88 theme overall 781:787 arg1 analysis 798:805 subgroup overall survival analysis 772:805 subgroup overall survival analysis 772:805 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 2 89 from value 290:294 arg1 carcinoma 317:325 esophagus carcinoma 307:325 esophagus carcinoma (ESCA) 307:332 Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). 36475339 2 89 from value 290:294 arg1 ESCA 328:331 ESCA 328:331 ESCA 328:331 Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). 36475339 8 90 theme BIN3 1134:1137 arg1 influence 1121:1129 The influence 1117:1129 The influence of BIN3 on epithelial-mesenchymal transition (EMT) 1117:1180 The influence of BIN3 on epithelial-mesenchymal transition (EMT) was validated by western blot. 36475339 10 91 theme BIN3 1485:1488 arg1 level 1495:1499 The BIN3 mRNA level 1481:1499 The BIN3 mRNA level 1481:1499 The BIN3 mRNA level was found to be significantly decreased in ESCA compared to normal tissues (p < 0.05). 36475339 16 92 theme N-cadherin 2542:2551 arg1 expression 2553:2562 N-cadherin expression 2542:2562 N-cadherin expression 2542:2562 In addition, BIN3 overexpression inhibited N-cadherin expression and promoted E-cadherin expression in ESCA cell lines TE-1. 36475339 5 93 theme analysis 798:805 arg1 expression 714:723 The expression 710:723 The expression of BIN3, pathological features correlation and subgroup overall survival analysis 710:805 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 12 94 theme columnar 1939:1946 arg1 No 1960:1961 No 1960:1961 No 1960:1961 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 94 theme columnar 1939:1946 arg1 metaplasia 1948:1957 columnar metaplasia 1939:1957 columnar metaplasia (No) of favorable OS 1939:1978 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 14 95 theme cell 2257:2260 arg1 development 2262:2272 beta cell development 2252:2272 beta cell development 2252:2272 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 17 96 from biomarker 2699:2707 arg1 ESCA 2712:2715 ESCA 2712:2715 ESCA 2712:2715 CONCLUSION These results suggest that BIN3 might be a potential prognostic biomarker in ESCA. 36475339 15 97 theme B 2425:2425 arg1 p 2434:2434 p < 0.001 2434:2442 p < 0.001 2434:2442 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 15 97 theme B 2425:2425 arg1 cells 2427:2431 B cells 2425:2431 B cells (p < 0.001) 2425:2443 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 8 98 theme epithelial-mesenchymal 1142:1163 arg1 EMT 1177:1179 EMT 1177:1179 EMT 1177:1179 The influence of BIN3 on epithelial-mesenchymal transition (EMT) was validated by western blot. 36475339 8 98 theme epithelial-mesenchymal 1142:1163 arg1 transition 1165:1174 epithelial-mesenchymal transition 1142:1174 epithelial-mesenchymal transition (EMT) 1142:1180 The influence of BIN3 on epithelial-mesenchymal transition (EMT) was validated by western blot. 36475339 0 99 with Patients 73:80 arg1 Carcinoma 97:105 Esophagus Carcinoma 87:105 Esophagus Carcinoma 87:105 Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data. 36475339 5 100 theme features 747:754 arg1 correlation 756:766 pathological features correlation 734:766 pathological features correlation 734:766 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 12 101 theme favorable 1967:1975 arg1 OS 1977:1978 favorable OS 1967:1978 favorable OS 1967:1978 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 15 102 theme Tregs 2406:2410 arg1 level 2376:2380 the infiltration level 2359:2380 the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001) 2359:2496 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 4 103 theme overall 610:616 arg1 OS 628:629 OS 628:629 OS 628:629 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 4 103 theme overall 610:616 arg1 survival 618:625 overall survival 610:625 overall survival (OS) 610:630 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 14 104 theme reactome 2229:2236 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 104 theme reactome 2229:2236 arg1 regulation 2238:2247 reactome regulation 2229:2247 reactome regulation of beta cell development 2229:2272 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 15 105 theme < 2458:2458 arg1 p 2456:2456 p < 0.001 2456:2464 p < 0.001 2456:2464 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 15 105 theme < 2458:2458 arg1 cells 2449:2453 NK cells 2446:2453 NK cells (p < 0.001) 2446:2465 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 4 106 theme expressed 578:586 arg1 genes 588:592 differentially expressed genes 563:592 differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) 563:699 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 11 107 theme p 1683:1683 arg1 stage 1676:1680 the clinical stage 1663:1680 the clinical stage (p = 0.015) 1663:1692 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 11 107 theme p 1683:1683 arg1 0.015 1687:1691 p = 0.015 1683:1691 p = 0.015 1683:1691 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 0 108 theme TCGA 125:128 arg1 Data 130:133 TCGA Data 125:133 TCGA Data 125:133 Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data. 36475339 5 109 theme Genome 839:844 arg1 Atlas 846:850 The Cancer Genome Atlas 828:850 The Cancer Genome Atlas (TCGA) 828:857 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 5 109 theme Genome 839:844 arg1 TCGA 853:856 TCGA 853:856 TCGA 853:856 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 4 110 theme disease-specific 633:648 arg1 survival 650:657 disease-specific survival 633:657 disease-specific survival (DSS) 633:663 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 4 110 theme disease-specific 633:648 arg1 DSS 660:662 DSS 660:662 DSS 660:662 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 15 111 theme < 2396:2396 arg1 cells 2387:2391 T cells 2385:2391 T cells (p < 0.001) 2385:2403 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 15 111 theme < 2396:2396 arg1 p 2394:2394 p < 0.001 2394:2402 p < 0.001 2394:2402 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 11 112 theme p 1751:1751 arg1 age 1746:1748 age 1746:1748 age (p < 0.05) 1746:1759 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 11 112 theme p 1751:1751 arg1 < 1753:1753 p < 0.05 1751:1758 p < 0.05 1751:1758 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 14 113 theme X 2209:2209 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 113 theme X 2209:2209 arg1 pathway 2220:2226 WP pregnane X receptor pathway 2197:2226 WP pregnane X receptor pathway 2197:2226 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 15 114 theme NK 2446:2447 arg1 p 2456:2456 p < 0.001 2456:2464 p < 0.001 2456:2464 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 15 114 theme NK 2446:2447 arg1 cells 2449:2453 NK cells 2446:2453 NK cells (p < 0.001) 2446:2465 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 8 115 theme western 1199:1205 arg1 blot 1207:1210 western blot 1199:1210 western blot 1199:1210 The influence of BIN3 on epithelial-mesenchymal transition (EMT) was validated by western blot. 36475339 0 116 theme Poor 55:58 arg1 Prognosis 60:68 a Poor Prognosis 53:68 a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data 53:133 Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data. 36475339 14 117 theme WP 2197:2198 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 117 theme WP 2197:2198 arg1 pathway 2220:2226 WP pregnane X receptor pathway 2197:2226 WP pregnane X receptor pathway 2197:2226 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 118 theme biocarta 2175:2182 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 118 theme biocarta 2175:2182 arg1 pathway 2188:2194 biocarta TFF pathway 2175:2194 biocarta TFF pathway 2175:2194 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 16 119 dep lines 2612:2616 arg1 TE-1 2618:2621 TE-1 2618:2621 TE-1 2618:2621 In addition, BIN3 overexpression inhibited N-cadherin expression and promoted E-cadherin expression in ESCA cell lines TE-1. 36475339 11 120 theme decreased 1592:1600 arg1 expression 1602:1611 The decreased expression 1588:1611 The decreased expression of BIN3 in ESCA 1588:1627 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 4 121 theme METHODS 430:436 arg1 Genes 438:442 METHODS Genes 430:442 METHODS Genes significantly correlated with the prognosis of ESCA patients 430:503 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 12 122 theme ESCA 1784:1787 arg1 patients 1789:1796 ESCA patients 1784:1796 ESCA patients with high BIN3 expression 1784:1822 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 6 123 theme signaling 903:911 arg1 pathways 913:920 the potential signaling pathways 889:920 the potential signaling pathways in which BIN3 was involved 889:947 Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). 36475339 12 124 theme therapy 1914:1920 arg1 outcome 1922:1928 primary therapy outcome 1906:1928 primary therapy outcome (PD) 1906:1933 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 124 theme therapy 1914:1920 arg1 PD 1931:1932 PD 1931:1932 PD 1931:1932 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 17 125 theme potential 2678:2686 arg1 BIN3 2662:2665 BIN3 2662:2665 BIN3 2662:2665 CONCLUSION These results suggest that BIN3 might be a potential prognostic biomarker in ESCA. 36475339 17 125 theme potential 2678:2686 arg1 biomarker 2699:2707 a potential prognostic biomarker 2676:2707 a potential prognostic biomarker in ESCA 2676:2715 CONCLUSION These results suggest that BIN3 might be a potential prognostic biomarker in ESCA. 36475339 16 126 theme BIN3 2512:2515 arg1 overexpression 2517:2530 BIN3 overexpression 2512:2530 BIN3 overexpression 2512:2530 In addition, BIN3 overexpression inhibited N-cadherin expression and promoted E-cadherin expression in ESCA cell lines TE-1. 36475339 9 127 theme overall 1373:1379 arg1 OS 1391:1392 OS 1391:1392 OS 1391:1392 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 9 127 theme overall 1373:1379 arg1 survival 1381:1388 overall survival 1373:1388 overall survival (OS) 1373:1393 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 6 128 theme gene 998:1001 arg1 analysis 1018:1025 gene set enrichment analysis 998:1025 gene set enrichment analysis (GSEA) 998:1032 Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). 36475339 6 128 theme gene 998:1001 arg1 GSEA 1028:1031 GSEA 1028:1031 GSEA 1028:1031 Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). 36475339 0 129 theme Integrator 9:18 arg1 Downregulation 29:42 Integrator 3 (BIN3) Downregulation 9:42 Bridging Integrator 3 (BIN3) Downregulation 0:42 Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data. 36475339 15 130 theme macrophage 2472:2481 arg1 M2 2483:2484 macrophage M2 2472:2484 macrophage M2 (p < 0.001) 2472:2496 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 15 130 theme macrophage 2472:2481 arg1 p 2487:2487 p < 0.001 2487:2495 p < 0.001 2487:2495 BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). 36475339 14 131 dep linked 2124:2129 arg1 O 2122:2122 O 2122:2122 O 2122:2122 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 5 132 theme GTEx 863:866 arg1 databases 868:876 GTEx databases 863:876 GTEx databases 863:876 The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. 36475339 6 133 theme GO-KEGG 966:972 arg1 analysis 985:992 GO-KEGG enrichment analysis 966:992 GO-KEGG enrichment analysis 966:992 Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). 36475339 4 134 theme ESCA 491:494 arg1 patients 496:503 ESCA patients 491:503 ESCA patients 491:503 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 12 135 theme T 1860:1860 arg1 T4 1874:1875 T3 & T4 1869:1875 T3 & T4 1869:1875 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 135 theme T 1860:1860 arg1 stage 1862:1866 T stage 1860:1866 T stage (T3 & T4) 1860:1876 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 4 136 theme progression-free 669:684 arg1 PFI 696:698 PFI 696:698 PFI 696:698 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 4 136 theme progression-free 669:684 arg1 interval 686:693 progression-free interval 669:693 progression-free interval (PFI) 669:699 METHODS Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. 36475339 3 137 theme prognostic 388:397 arg1 role 399:402 the pathological and prognostic role 367:402 the pathological and prognostic role of BIN3 in ESCA patients 367:427 This study aimed to investigate the pathological and prognostic role of BIN3 in ESCA patients. 36475339 14 138 theme HNF3B 2160:2164 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 138 theme HNF3B 2160:2164 arg1 pathway 2166:2172 PID HNF3B pathway 2156:2172 PID HNF3B pathway 2156:2172 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 16 139 theme cell 2607:2610 arg1 lines 2612:2616 ESCA cell lines TE-1 2602:2621 ESCA cell lines TE-1 2602:2621 In addition, BIN3 overexpression inhibited N-cadherin expression and promoted E-cadherin expression in ESCA cell lines TE-1. 36475339 3 140 theme pathological 371:382 arg1 role 399:402 the pathological and prognostic role 367:402 the pathological and prognostic role of BIN3 in ESCA patients 367:427 This study aimed to investigate the pathological and prognostic role of BIN3 in ESCA patients. 36475339 7 141 theme infiltrates 1042:1052 arg1 correlation 1054:1064 Immune infiltrates correlation 1035:1064 Immune infiltrates correlation of BIN3 in ESCA 1035:1080 Immune infiltrates correlation of BIN3 in ESCA was performed by TIMER and ssGSEA. 36475339 16 142 theme ESCA 2602:2605 arg1 lines 2612:2616 ESCA cell lines TE-1 2602:2621 ESCA cell lines TE-1 2602:2621 In addition, BIN3 overexpression inhibited N-cadherin expression and promoted E-cadherin expression in ESCA cell lines TE-1. 36475339 13 143 theme GO-KEGG 1981:1987 arg1 analysis 2000:2007 GO-KEGG enrichment analysis 1981:2007 GO-KEGG enrichment analysis 1981:2007 GO-KEGG enrichment analysis revealed that BIN3 was involved in endocytosis. 36475339 10 144 theme normal 1561:1566 arg1 tissues 1568:1574 normal tissues 1561:1574 normal tissues (p < 0.05) 1561:1585 The BIN3 mRNA level was found to be significantly decreased in ESCA compared to normal tissues (p < 0.05). 36475339 10 144 theme normal 1561:1566 arg1 < 1579:1579 p < 0.05 1577:1584 p < 0.05 1577:1584 The BIN3 mRNA level was found to be significantly decreased in ESCA compared to normal tissues (p < 0.05). 36475339 9 145 theme ESCA 1295:1298 arg1 patients 1300:1307 ESCA patients 1295:1307 ESCA patients 1295:1307 RESULTS There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. 36475339 14 146 theme linked 2124:2129 arg1 glycosylation 2131:2143 O linked glycosylation 2122:2143 O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others 2122:2322 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 147 theme Urea 2278:2281 arg1 mucins 2148:2153 mucins 2148:2153 mucins 2148:2153 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 14 147 theme Urea 2278:2281 arg1 cycle 2283:2287 WP Urea cycle 2275:2287 WP Urea cycle 2275:2287 GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. 36475339 12 148 theme & 1872:1872 arg1 T4 1874:1875 T3 & T4 1869:1875 T3 & T4 1869:1875 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 12 148 theme & 1872:1872 arg1 stage 1862:1866 T stage 1860:1866 T stage (T3 & T4) 1860:1876 ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. 36475339 11 149 theme p 1704:1704 arg1 stage 1697:1701 T stage 1695:1701 T stage (p < 0.05) 1695:1712 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 36475339 11 149 theme p 1704:1704 arg1 < 1706:1706 p < 0.05 1704:1711 p < 0.05 1704:1711 The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). 35420807 6 0 theme Ni-C 900:903 arg1 bonding 905:911 Ni-C bonding 900:911 Ni-C bonding 900:911 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 2 1 theme complexes 346:354 arg1 complexes 346:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 2 1 theme complexes 346:354 arg1 set 264:266 a set 262:266 a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 262:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 2 1 theme complexes 346:354 arg1 Ni-1-4 357:362 Ni-1-4 357:362 Ni-1-4 357:362 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 10 2 theme Ni-1 1572:1575 arg1 DSPE 1577:1580 Ni-1@DSPE 1572:1580 Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) 1572:1647 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 9 3 theme Proof-of-principle 1450:1467 arg1 experiments 1469:1479 Proof-of-principle experiments 1450:1479 Proof-of-principle experiments involving thrombus treatment 1450:1508 Proof-of-principle experiments involving thrombus treatment were carried out both in vitro and in vivo. 35420807 10 4 theme @ 1576:1576 arg1 DSPE 1577:1580 Ni-1@DSPE 1572:1580 Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) 1572:1647 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 7 5 theme TPBP 1126:1129 arg1 NiTPBP 1118:1123 NiTPBP 1118:1123 NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin) 1118:1169 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 7 5 theme TPBP 1126:1129 arg1 6,11,16,21-tetraphenylbenziporphyrin 1133:1168 TPBP = 6,11,16,21-tetraphenylbenziporphyrin 1126:1168 TPBP = 6,11,16,21-tetraphenylbenziporphyrin 1126:1168 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 11 6 theme excited-state 1915:1927 arg1 features 1929:1936 the excited-state features 1911:1936 the excited-state features of early transition-metal complexes 1911:1972 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 3 7 theme square-planar 445:457 arg1 geometry 472:479 a square-planar coordination geometry 443:479 a square-planar coordination geometry as inferred from the structural studies of Ni-1 443:527 Complexes Ni-1-4 are characterized by a square-planar coordination geometry as inferred from the structural studies of Ni-1. 35420807 11 8 theme π-conjugation 2005:2017 arg1 pathways 2019:2026 π-conjugation pathways 2005:2026 π-conjugation pathways 2005:2026 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 8 9 theme photothermal 1390:1401 arg1 efficiency 1414:1423 good photothermal conversion efficiency 1385:1423 good photothermal conversion efficiency (∼45%) 1385:1430 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 8 9 theme photothermal 1390:1401 arg1 % 1429:1429 ∼45% 1426:1429 ∼45% 1426:1429 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 7 10 theme theoretical 972:982 arg1 calculations 984:995 theoretical calculations 972:995 theoretical calculations 972:995 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 2 11 theme nonaromatic 280:290 arg1 complexes 346:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 11 12 theme present 1768:1774 arg1 work 1776:1779 The present work 1764:1779 The present work 1764:1779 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 8 13 theme Encapsulating 1172:1184 arg1 Ni-1 1186:1189 Encapsulating Ni-1 1172:1189 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) 1172:1293 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 8 14 theme good 1385:1388 arg1 efficiency 1414:1423 good photothermal conversion efficiency 1385:1423 good photothermal conversion efficiency (∼45%) 1385:1430 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 8 14 theme good 1385:1388 arg1 % 1429:1429 ∼45% 1426:1429 ∼45% 1426:1429 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 6 15 theme energy 801:806 arg1 absorption 808:817 the lowest energy absorption 790:817 the lowest energy absorption of Ni-1 790:825 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 6 15 theme energy 801:806 arg1 consequence 885:895 a consequence 883:895 a consequence of Ni-C bonding 883:911 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 2 16 theme O-linked 271:278 arg1 complexes 346:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 4 17 theme photoacoustic 593:605 arg1 PAI 616:618 PAI 616:618 PAI 616:618 They integrate photothermal therapy, photothermal imaging, and photoacoustic imaging (PAI) within one system. 35420807 4 17 theme photoacoustic 593:605 arg1 imaging 607:613 photoacoustic imaging 593:613 photoacoustic imaging (PAI) 593:619 They integrate photothermal therapy, photothermal imaging, and photoacoustic imaging (PAI) within one system. 35420807 10 18 theme 785 1602:1604 arg1 nm 1606:1607 nm 1606:1607 nm 1606:1607 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 8 19 theme red-shifted 1341:1351 arg1 features 1364:1371 red-shifted absorption features 1341:1371 red-shifted absorption features 1341:1371 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 6 20 theme lowest 794:799 arg1 absorption 808:817 the lowest energy absorption 790:817 the lowest energy absorption of Ni-1 790:825 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 6 20 theme lowest 794:799 arg1 consequence 885:895 a consequence 883:895 a consequence of Ni-C bonding 883:911 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 6 21 theme Ni 723:724 arg1 porphyrins 730:739 traditional Ni(II) porphyrins 711:739 traditional Ni(II) porphyrins 711:739 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 6 21 theme Ni 723:724 arg1 FTPP 750:753 FTPP 750:753 FTPP (tetrapentafluorophenylporphyrin) 750:787 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 2 22 theme σ-donating 383:392 arg1 bonds 398:402 strong σ-donating M-C bonds 376:402 strong σ-donating M-C bonds 376:402 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 9 23 theme thrombus 1491:1498 arg1 treatment 1500:1508 thrombus treatment 1491:1508 thrombus treatment 1491:1508 Proof-of-principle experiments involving thrombus treatment were carried out both in vitro and in vivo. 35420807 7 24 theme relative 1106:1113 arg1 Ni-1 1101:1104 Ni-1 1101:1104 Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin) 1101:1169 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 7 25 theme transient 924:932 arg1 spectroscopy 945:956 Ultrafast transient absorption spectroscopy 914:956 Ultrafast transient absorption spectroscopy combined with theoretical calculations 914:995 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 8 26 theme conversion 1403:1412 arg1 efficiency 1414:1423 good photothermal conversion efficiency 1385:1423 good photothermal conversion efficiency (∼45%) 1385:1430 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 8 26 theme conversion 1403:1412 arg1 % 1429:1429 ∼45% 1426:1429 ∼45% 1426:1429 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 6 27 theme traditional 711:721 arg1 porphyrins 730:739 traditional Ni(II) porphyrins 711:739 traditional Ni(II) porphyrins 711:739 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 6 27 theme traditional 711:721 arg1 FTPP 750:753 FTPP 750:753 FTPP (tetrapentafluorophenylporphyrin) 750:787 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 2 28 theme strong 376:381 arg1 bonds 398:402 strong σ-donating M-C bonds 376:402 strong σ-donating M-C bonds 376:402 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 8 29 theme polyethylene 1253:1264 arg1 glycol 1266:1271 polyethylene glycol)-2000 1253:1277 polyethylene glycol)-2000 1253:1277 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 8 29 theme polyethylene 1253:1264 arg1 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy 1194:1251 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy 1194:1251 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) 1194:1293 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 4 30 theme photothermal 567:578 arg1 imaging 580:586 photothermal imaging 567:586 photothermal imaging 567:586 They integrate photothermal therapy, photothermal imaging, and photoacoustic imaging (PAI) within one system. 35420807 11 31 theme potential 1837:1845 arg1 promise 1796:1802 the promise 1792:1802 the promise of organonickel(II) complexes 1792:1832 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 11 31 theme potential 1837:1845 arg1 theranostics 1847:1858 potential theranostics 1837:1858 potential theranostics 1837:1858 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 7 32 theme absorption 934:943 arg1 spectroscopy 945:956 Ultrafast transient absorption spectroscopy 914:956 Ultrafast transient absorption spectroscopy combined with theoretical calculations 914:995 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 10 33 dep model 1713:1717 arg1 monitored 1722:1730 monitored 1722:1730 monitored by photoacoustic imaging (PAI) 1722:1761 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 0 34 theme Nonaromatic 0:10 arg1 II 25:26 II 25:26 II 25:26 Nonaromatic Organonickel(II) Phototheranostics. 35420807 0 34 theme Nonaromatic 0:10 arg1 Organonickel 12:23 Nonaromatic Organonickel 0:23 Nonaromatic Organonickel(II) Phototheranostics. 0:46 Nonaromatic Organonickel(II) Phototheranostics. 35420807 11 35 theme organonickel 1807:1818 arg1 complexes 1824:1832 organonickel(II) complexes 1807:1832 organonickel(II) complexes 1807:1832 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 6 36 theme Ni-1 822:825 arg1 absorption 808:817 the lowest energy absorption 790:817 the lowest energy absorption of Ni-1 790:825 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 6 36 theme Ni-1 822:825 arg1 consequence 885:895 a consequence 883:895 a consequence of Ni-C bonding 883:911 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 10 37 theme thrombus 1704:1711 arg1 model 1713:1717 a mouse thrombus model 1696:1717 a mouse thrombus model as monitored by photoacoustic imaging (PAI) 1696:1761 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 2 38 theme C^N^N^N 308:314 arg1 complexes 346:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 6 39 theme infrared 852:859 arg1 region 861:866 the near infrared region 843:866 the near infrared region 843:866 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 10 40 theme mouse 1698:1702 arg1 model 1713:1717 a mouse thrombus model 1696:1717 a mouse thrombus model as monitored by photoacoustic imaging (PAI) 1696:1761 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 7 41 theme states 1083:1088 arg1 population 1043:1052 a higher population 1034:1052 a higher population of ligand-centered and 3MLCT states 1034:1088 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 7 42 theme Ultrafast 914:922 arg1 spectroscopy 945:956 Ultrafast transient absorption spectroscopy 914:956 Ultrafast transient absorption spectroscopy combined with theoretical calculations 914:995 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 1 43 theme diagnostic 111:120 arg1 functions 138:146 diagnostic and therapeutic functions 111:146 diagnostic and therapeutic functions 111:146 Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. 35420807 9 44 dep carried 1515:1521 arg1 out 1523:1525 out 1523:1525 out 1523:1525 Proof-of-principle experiments involving thrombus treatment were carried out both in vitro and in vivo. 35420807 3 45 theme coordination 459:470 arg1 geometry 472:479 a square-planar coordination geometry 443:479 a square-planar coordination geometry as inferred from the structural studies of Ni-1 443:527 Complexes Ni-1-4 are characterized by a square-planar coordination geometry as inferred from the structural studies of Ni-1. 35420807 10 46 from DSPE 1577:1580 arg1 combination 1585:1595 combination 1585:1595 combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) 1585:1647 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 2 47 theme benzitripyrrin 292:305 arg1 complexes 346:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 8 48 theme Ni-1 1319:1322 arg1 DSPE 1324:1327 Ni-1@DSPE 1319:1327 Ni-1@DSPE 1319:1327 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 3 49 theme structural 502:511 arg1 studies 513:519 the structural studies 498:519 the structural studies of Ni-1 498:527 Complexes Ni-1-4 are characterized by a square-planar coordination geometry as inferred from the structural studies of Ni-1. 35420807 2 50 link O-linked 271:278 arg1 complexes 346:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 2 51 contain containing 365:374 arg1 complexes 346:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 2 51 contain containing 365:374 arg1 set 264:266 a set 262:266 a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 262:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 2 51 contain containing 365:374 arg2 bonds 398:402 strong σ-donating M-C bonds 376:402 strong σ-donating M-C bonds 376:402 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 2 51 contain containing 365:374 arg1 Ni-1-4 357:362 Ni-1-4 357:362 Ni-1-4 357:362 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 8 52 theme aqueous 1435:1441 arg1 media 1443:1447 aqueous media 1435:1447 aqueous media 1435:1447 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 10 53 theme blood 1679:1683 arg1 clots 1685:1689 blood clots 1679:1689 blood clots 1679:1689 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 11 54 theme complexes 1824:1832 arg1 promise 1796:1802 the promise 1792:1802 the promise of organonickel(II) complexes 1792:1832 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 11 54 theme complexes 1824:1832 arg1 theranostics 1847:1858 potential theranostics 1837:1858 potential theranostics 1837:1858 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 11 54 theme complexes 1824:1832 arg1 benefits 1868:1875 the benefits 1864:1875 the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways 1864:2026 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 7 55 theme 3MLCT 1077:1081 arg1 states 1083:1088 ligand-centered and 3MLCT states 1057:1088 ligand-centered and 3MLCT states 1057:1088 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 6 56 theme near 847:850 arg1 region 861:866 the near infrared region 843:866 the near infrared region 843:866 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 1 57 theme low-cost 213:220 arg1 medicines 235:243 low-cost personalized medicines 213:243 low-cost personalized medicines 213:243 Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. 35420807 7 58 theme = 1131:1131 arg1 NiTPBP 1118:1123 NiTPBP 1118:1123 NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin) 1118:1169 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 7 58 theme = 1131:1131 arg1 6,11,16,21-tetraphenylbenziporphyrin 1133:1168 TPBP = 6,11,16,21-tetraphenylbenziporphyrin 1126:1168 TPBP = 6,11,16,21-tetraphenylbenziporphyrin 1126:1168 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 11 59 theme transition-metal 1947:1962 arg1 complexes 1964:1972 early transition-metal complexes 1941:1972 early transition-metal complexes 1941:1972 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 5 60 theme potential 670:678 arg1 phototheranostics 680:696 potential phototheranostics 670:696 potential phototheranostics 670:696 This makes them attractive as potential phototheranostics. 35420807 11 61 theme complexes 1964:1972 arg1 features 1929:1936 the excited-state features 1911:1936 the excited-state features of early transition-metal complexes 1911:1972 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 1 62 theme therapeutic 126:136 arg1 functions 138:146 diagnostic and therapeutic functions 111:146 diagnostic and therapeutic functions 111:146 Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. 35420807 10 63 theme photoacoustic 1735:1747 arg1 PAI 1758:1760 PAI 1758:1760 PAI 1758:1760 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 10 63 theme photoacoustic 1735:1747 arg1 imaging 1749:1755 photoacoustic imaging 1735:1755 photoacoustic imaging (PAI) 1735:1761 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 4 64 theme photothermal 545:556 arg1 therapy 558:564 photothermal therapy 545:564 photothermal therapy 545:564 They integrate photothermal therapy, photothermal imaging, and photoacoustic imaging (PAI) within one system. 35420807 7 65 theme ligand-centered 1057:1071 arg1 states 1083:1088 ligand-centered and 3MLCT states 1057:1088 ligand-centered and 3MLCT states 1057:1088 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 11 66 theme early 1941:1945 arg1 complexes 1964:1972 early transition-metal complexes 1941:1972 early transition-metal complexes 1941:1972 The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways. 35420807 3 67 dep geometry 472:479 arg1 inferred 484:491 inferred 484:491 inferred from the structural studies of Ni-1 484:527 Complexes Ni-1-4 are characterized by a square-planar coordination geometry as inferred from the structural studies of Ni-1. 35420807 7 68 theme higher 1036:1041 arg1 population 1043:1052 a higher population 1034:1052 a higher population of ligand-centered and 3MLCT states 1034:1088 Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). 35420807 2 69 theme organonickel 329:340 arg1 complexes 346:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 1 70 theme personalized 222:233 arg1 medicines 235:243 low-cost personalized medicines 213:243 low-cost personalized medicines 213:243 Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. 35420807 8 71 from Ni-1 1186:1189 arg1 glycol 1266:1271 polyethylene glycol)-2000 1253:1277 polyethylene glycol)-2000 1253:1277 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 8 71 from Ni-1 1186:1189 arg1 DSPE-PEG2000 1281:1292 DSPE-PEG2000 1281:1292 DSPE-PEG2000 1281:1292 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 8 71 from Ni-1 1186:1189 arg1 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy 1194:1251 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy 1194:1251 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) 1194:1293 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 1 72 theme metal-based 63:73 arg1 agents 89:94 agents 89:94 agents that integrate diagnostic and therapeutic functions within the same molecule 89:171 Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. 35420807 1 72 theme metal-based 63:73 arg1 theranostics 75:86 Earth-abundant metal-based theranostics 48:86 Earth-abundant metal-based theranostics 48:86 Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. 35420807 2 73 theme macrocyclic 317:327 arg1 complexes 346:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes 271:354 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 1 74 theme medicines 235:243 arg1 development 198:208 the development 194:208 the development of low-cost personalized medicines 194:243 Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. 35420807 2 75 theme M-C 394:396 arg1 bonds 398:402 strong σ-donating M-C bonds 376:402 strong σ-donating M-C bonds 376:402 Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. 35420807 8 76 theme @ 1323:1323 arg1 DSPE 1324:1327 Ni-1@DSPE 1319:1327 Ni-1@DSPE 1319:1327 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 1 77 theme same 159:162 arg1 molecule 164:171 the same molecule 155:171 the same molecule 155:171 Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. 35420807 8 78 theme absorption 1353:1362 arg1 features 1364:1371 red-shifted absorption features 1341:1371 red-shifted absorption features 1341:1371 Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (∼45%) in aqueous media. 35420807 6 79 theme bonding 905:911 arg1 absorption 808:817 the lowest energy absorption 790:817 the lowest energy absorption of Ni-1 790:825 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 6 79 theme bonding 905:911 arg1 consequence 885:895 a consequence 883:895 a consequence of Ni-C bonding 883:911 Relative to traditional Ni(II) porphyrins, such as FTPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. 35420807 1 80 theme Earth-abundant 48:61 arg1 agents 89:94 agents 89:94 agents that integrate diagnostic and therapeutic functions within the same molecule 89:171 Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. 35420807 1 80 theme Earth-abundant 48:61 arg1 theranostics 75:86 Earth-abundant metal-based theranostics 48:86 Earth-abundant metal-based theranostics 48:86 Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. 35420807 3 81 theme Ni-1 524:527 arg1 studies 513:519 the structural studies 498:519 the structural studies of Ni-1 498:527 Complexes Ni-1-4 are characterized by a square-planar coordination geometry as inferred from the structural studies of Ni-1. 35420807 10 82 with combination 1585:1595 arg1 photo-irradiation 1609:1625 785 nm photo-irradiation 1602:1625 785 nm photo-irradiation for 3 min (0.3 W/cm2) 1602:1647 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 35420807 10 83 theme nm 1606:1607 arg1 photo-irradiation 1609:1625 785 nm photo-irradiation 1602:1625 785 nm photo-irradiation for 3 min (0.3 W/cm2) 1602:1647 It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). 37247228 0 0 theme CDK9 114:117 arg1 inhibition 119:128 CDK9 inhibition 114:128 CDK9 inhibition 114:128 Identification of a diketopiperazine-based O-GlcNAc transferase inhibitor sensitizing hepatocellular carcinoma to CDK9 inhibition. 37247228 9 1 theme OGT 1356:1358 arg1 inhibitor 1360:1368 OGT inhibitor 1356:1368 OGT inhibitor 1356:1368 This work therefore demonstrates that HLY838 potentiates the antitumor responses of CDK9 inhibitor, providing an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics. 37247228 9 1 theme OGT 1356:1358 arg1 agent 1387:1391 a sensitizing agent 1373:1391 a sensitizing agent in cancer therapeutics 1373:1414 This work therefore demonstrates that HLY838 potentiates the antitumor responses of CDK9 inhibitor, providing an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics. 37247228 1 2 from process 235:241 arg1 cells 246:250 cells 246:250 cells 246:250 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 1 3 theme physiological 290:302 arg1 processes 304:312 physiological processes 290:312 physiological processes 290:312 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 8 4 theme protein 1190:1196 arg1 level 1198:1202 the protein level 1186:1202 the protein level 1186:1202 Mechanistically, c-Myc is regulated by the CDK9 at the transcript level, and stabilized by OGT at the protein level. 37247228 4 5 gly O-GlcNAcylation 645:659 arg1 carcinoma 699:707 hepatocellular carcinoma 684:707 hepatocellular carcinoma (HCC) 684:713 Previously, we and others demonstrated that O-GlcNAcylation is notably elevated in hepatocellular carcinoma (HCC). 37247228 4 5 gly O-GlcNAcylation 645:659 arg1 HCC 710:712 HCC 710:712 HCC 710:712 Previously, we and others demonstrated that O-GlcNAcylation is notably elevated in hepatocellular carcinoma (HCC). 37247228 2 6 theme only 386:389 arg1 enzyme 391:396 the only enzyme 382:396 the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins 382:466 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 1 7 theme processes 304:312 arg1 range 281:285 a wide range 274:285 a wide range of physiological processes 274:312 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 6 8 theme novel 845:849 arg1 inhibitor 878:886 a novel diketopiperazine-based OGT inhibitor 843:886 a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc 843:952 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 6 8 theme novel 845:849 arg1 HLY838 835:840 HLY838 835:840 HLY838 835:840 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 2 9 from cells 369:373 arg1 present 358:364 present 358:364 present 358:364 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 2 10 from present 358:364 arg1 cells 369:373 cells 369:373 cells 369:373 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 9 11 theme cancer 1396:1401 arg1 therapeutics 1403:1414 cancer therapeutics 1396:1414 cancer therapeutics 1396:1414 This work therefore demonstrates that HLY838 potentiates the antitumor responses of CDK9 inhibitor, providing an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics. 37247228 9 12 theme sensitizing 1375:1385 arg1 inhibitor 1360:1368 OGT inhibitor 1356:1368 OGT inhibitor 1356:1368 This work therefore demonstrates that HLY838 potentiates the antitumor responses of CDK9 inhibitor, providing an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics. 37247228 9 12 theme sensitizing 1375:1385 arg1 agent 1387:1391 a sensitizing agent 1373:1391 a sensitizing agent in cancer therapeutics 1373:1414 This work therefore demonstrates that HLY838 potentiates the antitumor responses of CDK9 inhibitor, providing an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics. 37247228 6 13 theme OGT 874:876 arg1 inhibitor 878:886 a novel diketopiperazine-based OGT inhibitor 843:886 a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc 843:952 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 6 13 theme OGT 874:876 arg1 HLY838 835:840 HLY838 835:840 HLY838 835:840 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 1 14 theme metabolic 225:233 arg1 O-GlcNAcylation 131:145 O-GlcNAcylation 131:145 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) 131:184 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 1 14 theme metabolic 225:233 arg1 process 235:241 an important post-translational and metabolic process 189:241 an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes 189:312 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 9 15 theme antitumor 1266:1274 arg1 responses 1276:1284 the antitumor responses 1262:1284 the antitumor responses of CDK9 inhibitor 1262:1302 This work therefore demonstrates that HLY838 potentiates the antitumor responses of CDK9 inhibitor, providing an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics. 37247228 6 16 theme diketopiperazine-based 851:872 arg1 inhibitor 878:886 a novel diketopiperazine-based OGT inhibitor 843:886 a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc 843:952 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 6 16 theme diketopiperazine-based 851:872 arg1 HLY838 835:840 HLY838 835:840 HLY838 835:840 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 6 17 from decrease 924:931 arg1 O-GlcNAc 945:952 cellular O-GlcNAc 936:952 cellular O-GlcNAc 936:952 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 2 18 located present 358:364 arg2 transferase 324:334 O-GlcNAc transferase 315:334 O-GlcNAc transferase (OGT) 315:340 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 2 18 located present 358:364 arg1 cells 369:373 cells 369:373 cells 369:373 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 2 18 located present 358:364 arg2 OGT 337:339 OGT 337:339 OGT 337:339 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 3 19 theme Aberrant 469:476 arg1 glycosylation 478:490 Aberrant glycosylation 469:490 Aberrant glycosylation by OGT 469:497 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 2 20 attach present 358:364 arg2 transferase 324:334 O-GlcNAc transferase 315:334 O-GlcNAc transferase (OGT) 315:340 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 2 20 attach present 358:364 arg1 cells 369:373 cells 369:373 cells 369:373 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 2 20 attach present 358:364 arg2 OGT 337:339 OGT 337:339 OGT 337:339 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 9 21 from agent 1387:1391 arg1 therapeutics 1403:1414 cancer therapeutics 1396:1414 cancer therapeutics 1396:1414 This work therefore demonstrates that HLY838 potentiates the antitumor responses of CDK9 inhibitor, providing an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics. 37247228 7 22 theme in 988:989 arg1 activity 1005:1012 the in vitro and in vivo anti-HCC activity 971:1012 the in vitro and in vivo anti-HCC activity of CDK9 inhibitor 971:1030 HLY838 enhances the in vitro and in vivo anti-HCC activity of CDK9 inhibitor by downregulating c-Myc and downstream E2F1 expression. 37247228 0 23 theme diketopiperazine-based 20:41 arg1 inhibitor 64:72 a diketopiperazine-based O-GlcNAc transferase inhibitor 18:72 a diketopiperazine-based O-GlcNAc transferase inhibitor 18:72 Identification of a diketopiperazine-based O-GlcNAc transferase inhibitor sensitizing hepatocellular carcinoma to CDK9 inhibition. 37247228 5 24 theme cancer 763:768 arg1 progression 770:780 cancer progression 763:780 cancer progression 763:780 The overexpression of O-GlcNAcylation promotes cancer progression and metastasis. 37247228 6 25 with inhibitor 878:886 arg1 ability 897:903 the ability to induce a global decrease in cellular O-GlcNAc 893:952 the ability to induce a global decrease in cellular O-GlcNAc 893:952 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 7 26 theme inhibitor 1022:1030 arg1 activity 1005:1012 the in vitro and in vivo anti-HCC activity 971:1012 the in vitro and in vivo anti-HCC activity of CDK9 inhibitor 971:1030 HLY838 enhances the in vitro and in vivo anti-HCC activity of CDK9 inhibitor by downregulating c-Myc and downstream E2F1 expression. 37247228 4 27 theme hepatocellular 684:697 arg1 carcinoma 699:707 hepatocellular carcinoma 684:707 hepatocellular carcinoma (HCC) 684:713 Previously, we and others demonstrated that O-GlcNAcylation is notably elevated in hepatocellular carcinoma (HCC). 37247228 4 27 theme hepatocellular 684:697 arg1 HCC 710:712 HCC 710:712 HCC 710:712 Previously, we and others demonstrated that O-GlcNAcylation is notably elevated in hepatocellular carcinoma (HCC). 37247228 6 28 theme cellular 936:943 arg1 O-GlcNAc 945:952 cellular O-GlcNAc 936:952 cellular O-GlcNAc 936:952 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 1 29 dep important 192:200 arg1 post-translational 202:219 post-translational 202:219 post-translational 202:219 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 7 30 theme CDK9 1017:1020 arg1 inhibitor 1022:1030 CDK9 inhibitor 1017:1030 CDK9 inhibitor 1017:1030 HLY838 enhances the in vitro and in vivo anti-HCC activity of CDK9 inhibitor by downregulating c-Myc and downstream E2F1 expression. 37247228 0 31 theme transferase 52:62 arg1 inhibitor 64:72 a diketopiperazine-based O-GlcNAc transferase inhibitor 18:72 a diketopiperazine-based O-GlcNAc transferase inhibitor 18:72 Identification of a diketopiperazine-based O-GlcNAc transferase inhibitor sensitizing hepatocellular carcinoma to CDK9 inhibition. 37247228 9 32 theme inhibitor 1294:1302 arg1 responses 1276:1284 the antitumor responses 1262:1284 the antitumor responses of CDK9 inhibitor 1262:1302 This work therefore demonstrates that HLY838 potentiates the antitumor responses of CDK9 inhibitor, providing an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics. 37247228 2 33 theme nucleocytoplasmic 441:457 arg1 proteins 459:466 nucleocytoplasmic proteins 441:466 nucleocytoplasmic proteins 441:466 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 2 34 theme O-GlcNAc 429:436 arg1 transfer 417:424 the transfer 413:424 the transfer of O-GlcNAc to nucleocytoplasmic proteins 413:466 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 0 35 theme O-GlcNAc 43:50 arg1 inhibitor 64:72 a diketopiperazine-based O-GlcNAc transferase inhibitor 18:72 a diketopiperazine-based O-GlcNAc transferase inhibitor 18:72 Identification of a diketopiperazine-based O-GlcNAc transferase inhibitor sensitizing hepatocellular carcinoma to CDK9 inhibition. 37247228 6 36 theme HLY838 835:840 arg1 identification 817:830 the identification 813:830 the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc 813:952 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 6 37 theme global 917:922 arg1 decrease 924:931 a global decrease 915:931 a global decrease in cellular O-GlcNAc 915:952 Here we report the identification of HLY838, a novel diketopiperazine-based OGT inhibitor with the ability to induce a global decrease in cellular O-GlcNAc. 37247228 5 38 theme O-GlcNAcylation 738:752 arg1 overexpression 720:733 The overexpression 716:733 The overexpression of O-GlcNAcylation 716:752 The overexpression of O-GlcNAcylation promotes cancer progression and metastasis. 37247228 1 39 theme O-linked 148:155 arg1 O-GlcNAcylation 131:145 O-GlcNAcylation 131:145 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) 131:184 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 1 39 theme O-linked 148:155 arg1 β-N-acetylglucosaminylation 157:183 O-linked β-N-acetylglucosaminylation 148:183 O-linked β-N-acetylglucosaminylation 148:183 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 0 40 theme inhibitor 64:72 arg1 Identification 0:13 Identification 0:13 Identification of a diketopiperazine-based O-GlcNAc transferase inhibitor 0:72 Identification of a diketopiperazine-based O-GlcNAc transferase inhibitor sensitizing hepatocellular carcinoma to CDK9 inhibition. 37247228 7 41 theme c-Myc 1050:1054 arg1 expression 1076:1085 c-Myc and downstream E2F1 expression 1050:1085 expression 1076:1085 HLY838 enhances the in vitro and in vivo anti-HCC activity of CDK9 inhibitor by downregulating c-Myc and downstream E2F1 expression. 37247228 8 42 theme transcript 1143:1152 arg1 level 1154:1158 the transcript level 1139:1158 the transcript level 1139:1158 Mechanistically, c-Myc is regulated by the CDK9 at the transcript level, and stabilized by OGT at the protein level. 37247228 9 43 theme experimental 1318:1329 arg1 rationale 1331:1339 an experimental rationale 1315:1339 an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics 1315:1414 This work therefore demonstrates that HLY838 potentiates the antitumor responses of CDK9 inhibitor, providing an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics. 37247228 7 44 theme E2F1 1071:1074 arg1 expression 1076:1085 c-Myc and downstream E2F1 expression 1050:1085 expression 1076:1085 HLY838 enhances the in vitro and in vivo anti-HCC activity of CDK9 inhibitor by downregulating c-Myc and downstream E2F1 expression. 37247228 3 45 theme diseases 531:538 arg1 diabetes 591:598 diabetes 591:598 diabetes 591:598 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 3 45 theme diseases 531:538 arg1 disorders 576:584 neurodegenerative disorders 558:584 neurodegenerative disorders 558:584 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 3 45 theme diseases 531:538 arg1 diseases 531:538 diseases 531:538 diseases including cancer, neurodegenerative disorders, and diabetes 531:598 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 3 45 theme diseases 531:538 arg1 variety 520:526 a variety 518:526 a variety of diseases including cancer, neurodegenerative disorders, and diabetes 518:598 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 3 45 theme diseases 531:538 arg1 cancer 550:555 cancer 550:555 cancer 550:555 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 1 46 link O-linked 148:155 arg1 O-GlcNAcylation 131:145 O-GlcNAcylation 131:145 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) 131:184 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 1 46 link O-linked 148:155 arg1 β-N-acetylglucosaminylation 157:183 O-linked β-N-acetylglucosaminylation 148:183 O-linked β-N-acetylglucosaminylation 148:183 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 7 47 theme anti-HCC 996:1003 arg1 activity 1005:1012 the in vitro and in vivo anti-HCC activity 971:1012 the in vitro and in vivo anti-HCC activity of CDK9 inhibitor 971:1030 HLY838 enhances the in vitro and in vivo anti-HCC activity of CDK9 inhibitor by downregulating c-Myc and downstream E2F1 expression. 37247228 2 48 theme O-GlcNAc 315:322 arg1 OGT 337:339 OGT 337:339 OGT 337:339 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 2 48 theme O-GlcNAc 315:322 arg1 transferase 324:334 O-GlcNAc transferase 315:334 O-GlcNAc transferase (OGT) 315:340 O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to nucleocytoplasmic proteins. 37247228 3 49 attach linked 508:513 arg1 cancer 550:555 cancer 550:555 cancer 550:555 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 3 49 attach linked 508:513 arg1 variety 520:526 a variety 518:526 a variety of diseases including cancer, neurodegenerative disorders, and diabetes 518:598 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 3 49 attach linked 508:513 arg1 disorders 576:584 neurodegenerative disorders 558:584 neurodegenerative disorders 558:584 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 3 49 attach linked 508:513 arg1 diseases 531:538 diseases 531:538 diseases including cancer, neurodegenerative disorders, and diabetes 531:598 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 3 49 attach linked 508:513 arg2 glycosylation 478:490 Aberrant glycosylation 469:490 Aberrant glycosylation by OGT 469:497 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 3 49 attach linked 508:513 arg1 diabetes 591:598 diabetes 591:598 diabetes 591:598 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 7 50 dep in 975:976 arg1 vitro 978:982 vitro 978:982 vitro 978:982 HLY838 enhances the in vitro and in vivo anti-HCC activity of CDK9 inhibitor by downregulating c-Myc and downstream E2F1 expression. 37247228 3 51 theme neurodegenerative 558:574 arg1 disorders 576:584 neurodegenerative disorders 558:584 neurodegenerative disorders 558:584 Aberrant glycosylation by OGT has been linked to a variety of diseases including cancer, neurodegenerative disorders, and diabetes. 37247228 1 52 theme wide 276:279 arg1 range 281:285 a wide range 274:285 a wide range of physiological processes 274:312 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 9 53 theme CDK9 1289:1292 arg1 inhibitor 1294:1302 CDK9 inhibitor 1289:1302 CDK9 inhibitor 1289:1302 This work therefore demonstrates that HLY838 potentiates the antitumor responses of CDK9 inhibitor, providing an experimental rationale for developing OGT inhibitor as a sensitizing agent in cancer therapeutics. 37247228 7 54 theme downstream 1060:1069 arg1 expression 1076:1085 c-Myc and downstream E2F1 expression 1050:1085 expression 1076:1085 HLY838 enhances the in vitro and in vivo anti-HCC activity of CDK9 inhibitor by downregulating c-Myc and downstream E2F1 expression. 37247228 7 55 theme in 975:976 arg1 activity 1005:1012 the in vitro and in vivo anti-HCC activity 971:1012 the in vitro and in vivo anti-HCC activity of CDK9 inhibitor 971:1030 HLY838 enhances the in vitro and in vivo anti-HCC activity of CDK9 inhibitor by downregulating c-Myc and downstream E2F1 expression. 37247228 0 56 theme hepatocellular 86:99 arg1 carcinoma 101:109 hepatocellular carcinoma 86:109 hepatocellular carcinoma 86:109 Identification of a diketopiperazine-based O-GlcNAc transferase inhibitor sensitizing hepatocellular carcinoma to CDK9 inhibition. 37247228 1 57 theme important 192:200 arg1 O-GlcNAcylation 131:145 O-GlcNAcylation 131:145 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) 131:184 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 1 57 theme important 192:200 arg1 process 235:241 an important post-translational and metabolic process 189:241 an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes 189:312 O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is an important post-translational and metabolic process in cells that is implicated in a wide range of physiological processes. 37247228 7 58 dep in 988:989 arg1 vivo 991:994 vivo 991:994 vivo 991:994 HLY838 enhances the in vitro and in vivo anti-HCC activity of CDK9 inhibitor by downregulating c-Myc and downstream E2F1 expression. 35879546 5 0 theme molecular 787:795 arg1 glue 797:800 a molecular glue 785:800 a molecular glue 785:800 Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. 35879546 8 1 theme MDH1 1199:1202 arg1 activity 1187:1194 the metabolic activity 1173:1194 the metabolic activity of MDH1 1173:1202 Our study reveals that O-GlcNAcylation contributes to pancreatic cancer growth by regulating the metabolic activity of MDH1. 35879546 5 2 theme monomeric 658:666 arg1 MDH1 668:671 monomeric MDH1 658:671 monomeric MDH1 658:671 Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. 35879546 3 3 theme Kras 330:333 arg1 mutation 335:342 Kras mutation 330:342 Kras mutation 330:342 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 5 4 theme Molecular 592:600 arg1 simulations 611:621 Molecular dynamics simulations 592:621 Molecular dynamics simulations 592:621 Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. 35879546 5 5 theme substrate 748:756 arg1 interactions 758:769 the substrate interactions 744:769 the substrate interactions 744:769 Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. 35879546 4 6 theme catabolic 508:516 arg1 pathway 518:524 the glutamine catabolic pathway 494:524 the glutamine catabolic pathway 494:524 Malate dehydrogenase 1 (MDH1), a key enzyme in the glutamine catabolic pathway, is positively regulated by O-GlcNAcylation on serine 189 (S189). 35879546 5 7 theme dynamics 602:609 arg1 simulations 611:621 Molecular dynamics simulations 592:621 Molecular dynamics simulations 592:621 Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. 35879546 4 8 theme key 480:482 arg1 enzyme 484:489 a key enzyme 478:489 a key enzyme in the glutamine catabolic pathway 478:524 Malate dehydrogenase 1 (MDH1), a key enzyme in the glutamine catabolic pathway, is positively regulated by O-GlcNAcylation on serine 189 (S189). 35879546 4 8 theme key 480:482 arg1 dehydrogenase 1 454:468 Malate dehydrogenase 1 447:468 Malate dehydrogenase 1 (MDH1) 447:475 Malate dehydrogenase 1 (MDH1), a key enzyme in the glutamine catabolic pathway, is positively regulated by O-GlcNAcylation on serine 189 (S189). 35879546 6 9 theme MDH1 840:843 arg1 activity 845:852 MDH1 activity 840:852 MDH1 activity 840:852 Depletion of O-GlcNAcylation reduces MDH1 activity, impairs glutamine metabolism, sensitizes PDAC cells to oxidative stress, decreases cell proliferation and inhibits tumor growth in nude mice. 35879546 3 10 link O-linked 361:368 arg1 form 416:419 a prevalent form 404:419 a prevalent form of protein glycosylation 404:444 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 3 10 link O-linked 361:368 arg1 O-GlcNAc 393:400 O-GlcNAc 393:400 O-GlcNAc 393:400 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 3 10 link O-linked 361:368 arg1 β-N-acetylglucosamine 370:390 cellular O-linked β-N-acetylglucosamine 352:390 cellular O-linked β-N-acetylglucosamine (O-GlcNAc) 352:401 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 3 11 theme cellular 352:359 arg1 form 416:419 a prevalent form 404:419 a prevalent form of protein glycosylation 404:444 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 3 11 theme cellular 352:359 arg1 O-GlcNAc 393:400 O-GlcNAc 393:400 O-GlcNAc 393:400 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 3 11 theme cellular 352:359 arg1 β-N-acetylglucosamine 370:390 cellular O-linked β-N-acetylglucosamine 352:390 cellular O-linked β-N-acetylglucosamine (O-GlcNAc) 352:401 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 1 12 theme catabolic 201:209 arg1 pathway 211:217 an unconventional glutamine catabolic pathway 173:217 an unconventional glutamine catabolic pathway 173:217 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 1 13 theme unconventional 176:189 arg1 pathway 211:217 an unconventional glutamine catabolic pathway 173:217 an unconventional glutamine catabolic pathway 173:217 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 3 14 theme O-linked 361:368 arg1 form 416:419 a prevalent form 404:419 a prevalent form of protein glycosylation 404:444 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 3 14 theme O-linked 361:368 arg1 O-GlcNAc 393:400 O-GlcNAc 393:400 O-GlcNAc 393:400 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 3 14 theme O-linked 361:368 arg1 β-N-acetylglucosamine 370:390 cellular O-linked β-N-acetylglucosamine 352:390 cellular O-linked β-N-acetylglucosamine (O-GlcNAc) 352:401 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 4 15 from enzyme 484:489 arg1 pathway 518:524 the glutamine catabolic pathway 494:524 the glutamine catabolic pathway 494:524 Malate dehydrogenase 1 (MDH1), a key enzyme in the glutamine catabolic pathway, is positively regulated by O-GlcNAcylation on serine 189 (S189). 35879546 6 16 theme O-GlcNAcylation 816:830 arg1 Depletion 803:811 Depletion 803:811 Depletion of O-GlcNAcylation 803:830 Depletion of O-GlcNAcylation reduces MDH1 activity, impairs glutamine metabolism, sensitizes PDAC cells to oxidative stress, decreases cell proliferation and inhibits tumor growth in nude mice. 35879546 1 17 theme Oncogenic 87:95 arg1 cells 152:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells 87:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells 87:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 1 18 theme glutamine 191:199 arg1 pathway 211:217 an unconventional glutamine catabolic pathway 173:217 an unconventional glutamine catabolic pathway 173:217 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 6 19 theme oxidative 910:918 arg1 stress 920:925 oxidative stress 910:925 oxidative stress 910:925 Depletion of O-GlcNAcylation reduces MDH1 activity, impairs glutamine metabolism, sensitizes PDAC cells to oxidative stress, decreases cell proliferation and inhibits tumor growth in nude mice. 35879546 1 20 theme Kras-activated 97:110 arg1 cells 152:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells 87:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells 87:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 3 21 theme glycosylation 432:444 arg1 form 416:419 a prevalent form 404:419 a prevalent form of protein glycosylation 404:444 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 3 21 theme glycosylation 432:444 arg1 β-N-acetylglucosamine 370:390 cellular O-linked β-N-acetylglucosamine 352:390 cellular O-linked β-N-acetylglucosamine (O-GlcNAc) 352:401 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 5 22 from glycosylation 641:653 arg1 MDH1 668:671 monomeric MDH1 658:671 monomeric MDH1 658:671 Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. 35879546 1 23 theme pancreatic 112:121 arg1 PDAC 146:149 PDAC 146:149 PDAC 146:149 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 1 23 theme pancreatic 112:121 arg1 adenocarcinoma 130:143 pancreatic ductal adenocarcinoma 112:143 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells 87:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 0 24 theme tumor 36:40 arg1 growth 42:47 pancreatic tumor growth 25:47 pancreatic tumor growth 25:47 O-GlcNAcylation promotes pancreatic tumor growth by regulating malate dehydrogenase 1. 35879546 5 25 theme pocket 721:726 arg1 stability 686:694 the stability 682:694 the stability of the substrate-binding pocket 682:726 Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. 35879546 1 26 theme ductal 123:128 arg1 PDAC 146:149 PDAC 146:149 PDAC 146:149 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 1 26 theme ductal 123:128 arg1 adenocarcinoma 130:143 pancreatic ductal adenocarcinoma 112:143 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells 87:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 0 27 theme pancreatic 25:34 arg1 growth 42:47 pancreatic tumor growth 25:47 pancreatic tumor growth 25:47 O-GlcNAcylation promotes pancreatic tumor growth by regulating malate dehydrogenase 1. 35879546 1 28 theme adenocarcinoma 130:143 arg1 cells 152:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells 87:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells 87:156 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 8 29 theme cancer 1145:1150 arg1 growth 1152:1157 pancreatic cancer growth 1134:1157 pancreatic cancer growth 1134:1157 Our study reveals that O-GlcNAcylation contributes to pancreatic cancer growth by regulating the metabolic activity of MDH1. 35879546 1 30 theme cell 230:233 arg1 growth 235:240 cell growth 230:240 cell growth 230:240 Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. 35879546 3 31 theme protein 424:430 arg1 glycosylation 432:444 protein glycosylation 424:444 protein glycosylation 424:444 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 6 32 theme nude 986:989 arg1 mice 991:994 nude mice 986:994 nude mice 986:994 Depletion of O-GlcNAcylation reduces MDH1 activity, impairs glutamine metabolism, sensitizes PDAC cells to oxidative stress, decreases cell proliferation and inhibits tumor growth in nude mice. 35879546 8 33 theme pancreatic 1134:1143 arg1 growth 1152:1157 pancreatic cancer growth 1134:1157 pancreatic cancer growth 1134:1157 Our study reveals that O-GlcNAcylation contributes to pancreatic cancer growth by regulating the metabolic activity of MDH1. 35879546 6 34 theme PDAC 896:899 arg1 cells 901:905 PDAC cells 896:905 PDAC cells 896:905 Depletion of O-GlcNAcylation reduces MDH1 activity, impairs glutamine metabolism, sensitizes PDAC cells to oxidative stress, decreases cell proliferation and inhibits tumor growth in nude mice. 35879546 5 35 gly glycosylation 641:653 arg1 MDH1 668:671 monomeric MDH1 658:671 monomeric MDH1 658:671 Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. 35879546 3 36 theme prevalent 406:414 arg1 form 416:419 a prevalent form 404:419 a prevalent form of protein glycosylation 404:444 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 3 36 theme prevalent 406:414 arg1 β-N-acetylglucosamine 370:390 cellular O-linked β-N-acetylglucosamine 352:390 cellular O-linked β-N-acetylglucosamine (O-GlcNAc) 352:401 Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. 35879546 6 37 from growth 976:981 arg1 mice 991:994 nude mice 986:994 nude mice 986:994 Depletion of O-GlcNAcylation reduces MDH1 activity, impairs glutamine metabolism, sensitizes PDAC cells to oxidative stress, decreases cell proliferation and inhibits tumor growth in nude mice. 35879546 8 38 theme metabolic 1177:1185 arg1 activity 1187:1194 the metabolic activity 1173:1194 the metabolic activity of MDH1 1173:1202 Our study reveals that O-GlcNAcylation contributes to pancreatic cancer growth by regulating the metabolic activity of MDH1. 35879546 7 39 theme clinical 1057:1064 arg1 samples 1071:1077 clinical PDAC samples 1057:1077 clinical PDAC samples 1057:1077 Furthermore, O-GlcNAcylation levels of MDH1 are elevated in clinical PDAC samples. 35879546 6 40 theme cell 938:941 arg1 proliferation 943:955 cell proliferation 938:955 cell proliferation 938:955 Depletion of O-GlcNAcylation reduces MDH1 activity, impairs glutamine metabolism, sensitizes PDAC cells to oxidative stress, decreases cell proliferation and inhibits tumor growth in nude mice. 35879546 5 41 theme S189 636:639 arg1 glycosylation 641:653 S189 glycosylation 636:653 S189 glycosylation on monomeric MDH1 636:671 Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. 35879546 6 42 theme tumor 970:974 arg1 growth 976:981 tumor growth 970:981 tumor growth in nude mice 970:994 Depletion of O-GlcNAcylation reduces MDH1 activity, impairs glutamine metabolism, sensitizes PDAC cells to oxidative stress, decreases cell proliferation and inhibits tumor growth in nude mice. 35879546 7 43 theme PDAC 1066:1069 arg1 samples 1071:1077 clinical PDAC samples 1057:1077 clinical PDAC samples 1057:1077 Furthermore, O-GlcNAcylation levels of MDH1 are elevated in clinical PDAC samples. 35879546 5 44 theme substrate-binding 703:719 arg1 pocket 721:726 the substrate-binding pocket 699:726 the substrate-binding pocket 699:726 Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. 35879546 6 45 theme glutamine 863:871 arg1 metabolism 873:882 glutamine metabolism 863:882 glutamine metabolism 863:882 Depletion of O-GlcNAcylation reduces MDH1 activity, impairs glutamine metabolism, sensitizes PDAC cells to oxidative stress, decreases cell proliferation and inhibits tumor growth in nude mice. 35879546 4 46 theme Malate 447:452 arg1 enzyme 484:489 a key enzyme 478:489 a key enzyme in the glutamine catabolic pathway 478:524 Malate dehydrogenase 1 (MDH1), a key enzyme in the glutamine catabolic pathway, is positively regulated by O-GlcNAcylation on serine 189 (S189). 35879546 4 46 theme Malate 447:452 arg1 MDH1 471:474 MDH1 471:474 MDH1 471:474 Malate dehydrogenase 1 (MDH1), a key enzyme in the glutamine catabolic pathway, is positively regulated by O-GlcNAcylation on serine 189 (S189). 35879546 4 46 theme Malate 447:452 arg1 dehydrogenase 1 454:468 Malate dehydrogenase 1 447:468 Malate dehydrogenase 1 (MDH1) 447:475 Malate dehydrogenase 1 (MDH1), a key enzyme in the glutamine catabolic pathway, is positively regulated by O-GlcNAcylation on serine 189 (S189). 35879546 7 47 theme MDH1 1036:1039 arg1 levels 1026:1031 O-GlcNAcylation levels 1010:1031 O-GlcNAcylation levels of MDH1 1010:1039 Furthermore, O-GlcNAcylation levels of MDH1 are elevated in clinical PDAC samples. 35879546 0 48 theme malate 63:68 arg1 dehydrogenase 70:82 malate dehydrogenase 1 63:84 malate dehydrogenase 1 63:84 O-GlcNAcylation promotes pancreatic tumor growth by regulating malate dehydrogenase 1. 35879546 4 49 theme glutamine 498:506 arg1 pathway 518:524 the glutamine catabolic pathway 494:524 the glutamine catabolic pathway 494:524 Malate dehydrogenase 1 (MDH1), a key enzyme in the glutamine catabolic pathway, is positively regulated by O-GlcNAcylation on serine 189 (S189). 35879546 7 50 theme O-GlcNAcylation 1010:1024 arg1 levels 1026:1031 O-GlcNAcylation levels 1010:1031 O-GlcNAcylation levels of MDH1 1010:1039 Furthermore, O-GlcNAcylation levels of MDH1 are elevated in clinical PDAC samples. 37107519 2 0 theme SDF 526:528 arg1 kinds 517:521 two kinds 513:521 two kinds of SDF 513:528 Based on this, the contribution of two kinds of SDF to the texture and microstructure of jelly was further examined. 37107519 7 1 theme mixed 1069:1073 arg1 fermentation 1087:1098 the mixed solid-state fermentation 1065:1098 the mixed solid-state fermentation 1065:1098 The above results pointed out that the mixed solid-state fermentation contributed to alteration of the SDF structure. 37107519 1 2 theme functional 373:382 arg1 characteristics 384:398 the structural and functional characteristics 354:398 the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF 354:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 2 3 theme kinds 517:521 arg1 contribution 497:508 the contribution 493:508 the contribution of two kinds of SDF to the texture and microstructure of jelly 493:571 Based on this, the contribution of two kinds of SDF to the texture and microstructure of jelly was further examined. 37107519 1 4 theme navel 219:223 arg1 NOP-IDF 238:244 NOP-IDF 238:244 NOP-IDF 238:244 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 4 theme navel 219:223 arg1 peel 232:235 navel orange peel 219:235 navel orange peel (NOP-IDF) 219:245 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 8 5 theme oil 1192:1194 arg1 capacity 1204:1211 oil holding capacity 1192:1211 oil holding capacity 1192:1211 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 12 6 theme structural 1810:1819 arg1 properties 1836:1845 much excellent structural and functional properties 1795:1845 much excellent structural and functional properties 1795:1845 In general, M-SDF displayed much excellent structural and functional properties, which could be utilized to develop functional food. 37107519 3 7 theme microscopy 629:638 arg1 analysis 599:606 The analysis 595:606 The analysis of scanning electron microscopy 595:638 The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. 37107519 9 8 theme cholesterol 1342:1352 arg1 capacity 1365:1372 the cholesterol adsorption capacity 1338:1372 the cholesterol adsorption capacity of M-SDF 1338:1381 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 9 8 theme cholesterol 1342:1352 arg1 highest 1387:1393 highest 1387:1393 highest 1387:1393 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 3 9 theme loose 673:677 arg1 structure 679:687 a loose structure 671:687 a loose structure 671:687 The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. 37107519 7 10 theme above 1034:1038 arg1 results 1040:1046 The above results 1030:1046 The above results 1030:1046 The above results pointed out that the mixed solid-state fermentation contributed to alteration of the SDF structure. 37107519 8 11 theme M-SDF 1216:1220 arg1 capacity 1204:1211 oil holding capacity 1192:1211 oil holding capacity 1192:1211 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 8 11 theme M-SDF 1216:1220 arg1 capacity 1179:1186 water holding capacity 1165:1186 water holding capacity 1165:1186 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 1 12 theme dietary 165:171 arg1 SDFs 181:184 SDFs 181:184 SDFs 181:184 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 12 theme dietary 165:171 arg1 fibers 173:178 soluble dietary fibers 157:178 soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) 157:245 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 8 13 theme water 1165:1169 arg1 capacity 1179:1186 water holding capacity 1165:1186 water holding capacity 1165:1186 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 11 14 theme mesh 1696:1699 arg1 structure 1701:1709 a homogeneous porous mesh structure 1675:1709 a homogeneous porous mesh structure 1675:1709 At the same time, the jelly added with M-SDF performed a homogeneous porous mesh structure, which contributed to keeping the texture of the jelly. 37107519 0 15 theme Jelly 114:118 arg1 Quality 103:109 the Quality 99:109 the Quality of Jelly 99:118 Effect of Soluble Dietary Fiber of Navel Orange Peel Prepared by Mixed Solid-State Fermentation on the Quality of Jelly. 37107519 1 16 theme fermentation 325:336 arg1 modification 338:349 fermentation modification 325:349 fermentation modification 325:349 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 7 17 dep pointed 1048:1054 arg1 out 1056:1058 out 1056:1058 out 1056:1058 The above results pointed out that the mixed solid-state fermentation contributed to alteration of the SDF structure. 37107519 11 18 theme homogeneous 1677:1687 arg1 structure 1701:1709 a homogeneous porous mesh structure 1675:1709 a homogeneous porous mesh structure 1675:1709 At the same time, the jelly added with M-SDF performed a homogeneous porous mesh structure, which contributed to keeping the texture of the jelly. 37107519 5 19 theme thermal 854:860 arg1 stability 862:870 thermal stability 854:870 thermal stability 854:870 In addition, M-SDF exhibited increased molecular weight and elevated thermal stability, and had significantly higher relative crystallinity than U-SDF. 37107519 11 20 theme same 1627:1630 arg1 time 1632:1635 the same time 1623:1635 the same time 1623:1635 At the same time, the jelly added with M-SDF performed a homogeneous porous mesh structure, which contributed to keeping the texture of the jelly. 37107519 1 21 theme structural 358:367 arg1 characteristics 384:398 the structural and functional characteristics 354:398 the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF 354:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 0 22 theme Peel 48:51 arg1 Fiber 26:30 Soluble Dietary Fiber 10:30 Soluble Dietary Fiber of Navel Orange Peel 10:51 Effect of Soluble Dietary Fiber of Navel Orange Peel Prepared by Mixed Solid-State Fermentation on the Quality of Jelly. 37107519 9 23 theme ± 1412:1412 arg1 g/g 1419:1421 12.88 ± 0.15 g/g 1406:1421 12.88 ± 0.15 g/g 1406:1421 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 6 24 theme monosaccharide 963:976 arg1 composition 978:988 monosaccharide composition 963:988 monosaccharide composition 963:988 Fermentation modified the monosaccharide composition and ratio of SDF, as compared to U-SDF. 37107519 2 25 theme jelly 567:571 arg1 microstructure 549:562 microstructure 549:562 microstructure 549:562 Based on this, the contribution of two kinds of SDF to the texture and microstructure of jelly was further examined. 37107519 2 25 theme jelly 567:571 arg1 texture 537:543 texture 537:543 texture 537:543 Based on this, the contribution of two kinds of SDF to the texture and microstructure of jelly was further examined. 37107519 0 26 theme Solid-State 71:81 arg1 Fermentation 83:94 Mixed Solid-State Fermentation 65:94 Mixed Solid-State Fermentation on the Quality of Jelly 65:118 Effect of Soluble Dietary Fiber of Navel Orange Peel Prepared by Mixed Solid-State Fermentation on the Quality of Jelly. 37107519 10 27 theme higher 1539:1544 arg1 hardness 1546:1553 a higher hardness 1537:1553 a higher hardness of 751.15 1537:1563 In addition, jellies containing M-SDF exhibited a higher hardness of 751.15 than U-SDF, as well as better gumminess and chewiness. 37107519 7 28 theme SDF 1133:1135 arg1 structure 1137:1145 the SDF structure 1129:1145 the SDF structure 1129:1145 The above results pointed out that the mixed solid-state fermentation contributed to alteration of the SDF structure. 37107519 1 29 theme orange 225:230 arg1 NOP-IDF 238:244 NOP-IDF 238:244 NOP-IDF 238:244 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 29 theme orange 225:230 arg1 peel 232:235 navel orange peel 219:235 navel orange peel (NOP-IDF) 219:245 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 9 30 theme glucose 1460:1466 arg1 capacity 1479:1486 better glucose adsorption capacity 1453:1486 better glucose adsorption capacity 1453:1486 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 8 31 dep capacity 1179:1186 arg1 the 1161:1163 the 1161:1163 the 1161:1163 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 0 32 theme Soluble 10:16 arg1 Fiber 26:30 Soluble Dietary Fiber 10:30 Soluble Dietary Fiber of Navel Orange Peel 10:51 Effect of Soluble Dietary Fiber of Navel Orange Peel Prepared by Mixed Solid-State Fermentation on the Quality of Jelly. 37107519 5 33 theme higher 895:900 arg1 crystallinity 911:923 significantly higher relative crystallinity 881:923 significantly higher relative crystallinity 881:923 In addition, M-SDF exhibited increased molecular weight and elevated thermal stability, and had significantly higher relative crystallinity than U-SDF. 37107519 1 34 with comparison 410:419 arg1 fiber 452:456 untreated soluble dietary fiber 426:456 untreated soluble dietary fiber (U-SDF) of NOP-IDF 426:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 34 with comparison 410:419 arg1 U-SDF 459:463 U-SDF 459:463 U-SDF 459:463 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 0 35 theme Fiber 26:30 arg1 Effect 0:5 Effect 0:5 Effect of Soluble Dietary Fiber of Navel Orange Peel 0:51 Effect of Soluble Dietary Fiber of Navel Orange Peel Prepared by Mixed Solid-State Fermentation on the Quality of Jelly. 37107519 1 36 theme dietary 444:450 arg1 fiber 452:456 untreated soluble dietary fiber 426:456 untreated soluble dietary fiber (U-SDF) of NOP-IDF 426:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 36 theme dietary 444:450 arg1 U-SDF 459:463 U-SDF 459:463 U-SDF 459:463 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 10 37 theme better 1588:1593 arg1 gumminess 1595:1603 better gumminess 1588:1603 better gumminess 1588:1603 In addition, jellies containing M-SDF exhibited a higher hardness of 751.15 than U-SDF, as well as better gumminess and chewiness. 37107519 1 38 theme mixed 250:254 arg1 M-SDF 282:286 M-SDF 282:286 M-SDF 282:286 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 38 theme mixed 250:254 arg1 fermentation 268:279 mixed solid-state fermentation 250:279 mixed solid-state fermentation (M-SDF) 250:287 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 8 39 dep 5.04 1247:1250 arg1 ± 1252:1252 ± 1252:1252 ± 1252:1252 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 4 40 theme electron 715:722 arg1 microscopy 724:733 scanning electron microscopy 706:733 scanning electron microscopy 706:733 The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. 37107519 10 41 contain containing 1510:1519 arg2 M-SDF 1521:1525 M-SDF 1521:1525 M-SDF 1521:1525 In addition, jellies containing M-SDF exhibited a higher hardness of 751.15 than U-SDF, as well as better gumminess and chewiness. 37107519 10 41 contain containing 1510:1519 arg1 jellies 1502:1508 jellies 1502:1508 jellies containing M-SDF 1502:1525 In addition, jellies containing M-SDF exhibited a higher hardness of 751.15 than U-SDF, as well as better gumminess and chewiness. 37107519 1 42 from comparison 410:419 arg1 characteristics 384:398 the structural and functional characteristics 354:398 the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF 354:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 43 from SDF 403:405 arg1 comparison 410:419 comparison 410:419 comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF 410:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 3 44 theme electron 620:627 arg1 microscopy 629:638 scanning electron microscopy 611:638 scanning electron microscopy 611:638 The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. 37107519 1 45 theme NOP-IDF 469:475 arg1 fiber 452:456 untreated soluble dietary fiber 426:456 untreated soluble dietary fiber (U-SDF) of NOP-IDF 426:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 45 theme NOP-IDF 469:475 arg1 U-SDF 459:463 U-SDF 459:463 U-SDF 459:463 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 46 theme dietary 202:208 arg1 fiber 210:214 insoluble dietary fiber 192:214 insoluble dietary fiber of navel orange peel (NOP-IDF) 192:245 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 47 from characteristics 384:398 arg1 comparison 410:419 comparison 410:419 comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF 410:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 12 48 used utilized 1863:1870 arg2 properties 1836:1845 much excellent structural and functional properties 1795:1845 much excellent structural and functional properties 1795:1845 In general, M-SDF displayed much excellent structural and functional properties, which could be utilized to develop functional food. 37107519 1 49 theme SDF 403:405 arg1 characteristics 384:398 the structural and functional characteristics 354:398 the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF 354:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 50 theme work 137:140 arg1 aim 125:127 The aim 121:127 The aim of this work 121:140 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 4 51 theme loose 768:772 arg1 structure 774:782 a loose structure 766:782 a loose structure 766:782 The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. 37107519 9 52 theme adsorption 1354:1363 arg1 capacity 1365:1372 the cholesterol adsorption capacity 1338:1372 the cholesterol adsorption capacity of M-SDF 1338:1381 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 9 52 theme adsorption 1354:1363 arg1 highest 1387:1393 highest 1387:1393 highest 1387:1393 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 12 53 theme functional 1825:1834 arg1 properties 1836:1845 much excellent structural and functional properties 1795:1845 much excellent structural and functional properties 1795:1845 In general, M-SDF displayed much excellent structural and functional properties, which could be utilized to develop functional food. 37107519 8 54 theme holding 1196:1202 arg1 capacity 1204:1211 oil holding capacity 1192:1211 oil holding capacity 1192:1211 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 1 55 theme untreated 426:434 arg1 fiber 452:456 untreated soluble dietary fiber 426:456 untreated soluble dietary fiber (U-SDF) of NOP-IDF 426:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 55 theme untreated 426:434 arg1 U-SDF 459:463 U-SDF 459:463 U-SDF 459:463 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 56 theme soluble 157:163 arg1 SDFs 181:184 SDFs 181:184 SDFs 181:184 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 56 theme soluble 157:163 arg1 fibers 173:178 soluble dietary fibers 157:178 soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) 157:245 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 5 57 contain had 877:879 arg2 crystallinity 911:923 significantly higher relative crystallinity 881:923 significantly higher relative crystallinity 881:923 In addition, M-SDF exhibited increased molecular weight and elevated thermal stability, and had significantly higher relative crystallinity than U-SDF. 37107519 5 57 contain had 877:879 arg1 M-SDF 798:802 M-SDF 798:802 M-SDF 798:802 In addition, M-SDF exhibited increased molecular weight and elevated thermal stability, and had significantly higher relative crystallinity than U-SDF. 37107519 12 58 theme much 1795:1798 arg1 properties 1836:1845 much excellent structural and functional properties 1795:1845 much excellent structural and functional properties 1795:1845 In general, M-SDF displayed much excellent structural and functional properties, which could be utilized to develop functional food. 37107519 1 59 theme modification 338:349 arg1 influence 312:320 the influence 308:320 the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF 308:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 8 60 theme holding 1171:1177 arg1 capacity 1179:1186 water holding capacity 1165:1186 water holding capacity 1165:1186 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 11 61 theme porous 1689:1694 arg1 structure 1701:1709 a homogeneous porous mesh structure 1675:1709 a homogeneous porous mesh structure 1675:1709 At the same time, the jelly added with M-SDF performed a homogeneous porous mesh structure, which contributed to keeping the texture of the jelly. 37107519 0 62 from Fermentation 83:94 arg1 Quality 103:109 the Quality 99:109 the Quality of Jelly 99:118 Effect of Soluble Dietary Fiber of Navel Orange Peel Prepared by Mixed Solid-State Fermentation on the Quality of Jelly. 37107519 8 63 dep 5.68 1227:1230 arg1 times 1285:1289 about six times 1275:1289 about six times 1275:1289 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 8 63 dep 5.68 1227:1230 arg1 ± 1232:1232 ± 1232:1232 ± 1232:1232 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 8 63 dep 5.68 1227:1230 arg1 times 1299:1303 two times 1295:1303 two times of U-SDF 1295:1312 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 5 64 theme molecular 824:832 arg1 weight 834:839 increased molecular weight 814:839 increased molecular weight 814:839 In addition, M-SDF exhibited increased molecular weight and elevated thermal stability, and had significantly higher relative crystallinity than U-SDF. 37107519 5 65 theme increased 814:822 arg1 weight 834:839 increased molecular weight 814:839 increased molecular weight 814:839 In addition, M-SDF exhibited increased molecular weight and elevated thermal stability, and had significantly higher relative crystallinity than U-SDF. 37107519 0 66 theme Mixed 65:69 arg1 Fermentation 83:94 Mixed Solid-State Fermentation 65:94 Mixed Solid-State Fermentation on the Quality of Jelly 65:118 Effect of Soluble Dietary Fiber of Navel Orange Peel Prepared by Mixed Solid-State Fermentation on the Quality of Jelly. 37107519 9 67 theme 0.15 1414:1417 arg1 g/g 1419:1421 12.88 ± 0.15 g/g 1406:1421 12.88 ± 0.15 g/g 1406:1421 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 4 68 theme scanning 706:713 arg1 microscopy 724:733 scanning electron microscopy 706:733 scanning electron microscopy 706:733 The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. 37107519 5 69 theme relative 902:909 arg1 crystallinity 911:923 significantly higher relative crystallinity 881:923 significantly higher relative crystallinity 881:923 In addition, M-SDF exhibited increased molecular weight and elevated thermal stability, and had significantly higher relative crystallinity than U-SDF. 37107519 6 70 dep composition 978:988 arg1 the 959:961 the 959:961 the 959:961 Fermentation modified the monosaccharide composition and ratio of SDF, as compared to U-SDF. 37107519 1 71 from influence 312:320 arg1 characteristics 384:398 the structural and functional characteristics 354:398 the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF 354:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 9 72 theme M-SDF 1377:1381 arg1 capacity 1365:1372 the cholesterol adsorption capacity 1338:1372 the cholesterol adsorption capacity of M-SDF 1338:1381 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 9 72 theme M-SDF 1377:1381 arg1 highest 1387:1393 highest 1387:1393 highest 1387:1393 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 12 73 theme excellent 1800:1808 arg1 properties 1836:1845 much excellent structural and functional properties 1795:1845 much excellent structural and functional properties 1795:1845 In general, M-SDF displayed much excellent structural and functional properties, which could be utilized to develop functional food. 37107519 7 74 theme structure 1137:1145 arg1 alteration 1115:1124 alteration 1115:1124 alteration of the SDF structure 1115:1145 The above results pointed out that the mixed solid-state fermentation contributed to alteration of the SDF structure. 37107519 9 75 theme better 1453:1458 arg1 capacity 1479:1486 better glucose adsorption capacity 1453:1486 better glucose adsorption capacity 1453:1486 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 11 76 theme jelly 1760:1764 arg1 texture 1745:1751 the texture 1741:1751 the texture of the jelly 1741:1764 At the same time, the jelly added with M-SDF performed a homogeneous porous mesh structure, which contributed to keeping the texture of the jelly. 37107519 0 77 theme Dietary 18:24 arg1 Fiber 26:30 Soluble Dietary Fiber 10:30 Soluble Dietary Fiber of Navel Orange Peel 10:51 Effect of Soluble Dietary Fiber of Navel Orange Peel Prepared by Mixed Solid-State Fermentation on the Quality of Jelly. 37107519 1 78 theme peel 232:235 arg1 fiber 210:214 insoluble dietary fiber 192:214 insoluble dietary fiber of navel orange peel (NOP-IDF) 192:245 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 9 79 theme adsorption 1468:1477 arg1 capacity 1479:1486 better glucose adsorption capacity 1453:1486 better glucose adsorption capacity 1453:1486 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 6 80 theme SDF 1003:1005 arg1 composition 978:988 monosaccharide composition 963:988 monosaccharide composition 963:988 Fermentation modified the monosaccharide composition and ratio of SDF, as compared to U-SDF. 37107519 6 80 theme SDF 1003:1005 arg1 ratio 994:998 ratio 994:998 ratio 994:998 Fermentation modified the monosaccharide composition and ratio of SDF, as compared to U-SDF. 37107519 1 81 theme soluble 436:442 arg1 fiber 452:456 untreated soluble dietary fiber 426:456 untreated soluble dietary fiber (U-SDF) of NOP-IDF 426:475 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 81 theme soluble 436:442 arg1 U-SDF 459:463 U-SDF 459:463 U-SDF 459:463 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 10 82 theme 751.15 1558:1563 arg1 hardness 1546:1553 a higher hardness 1537:1553 a higher hardness of 751.15 1537:1563 In addition, jellies containing M-SDF exhibited a higher hardness of 751.15 than U-SDF, as well as better gumminess and chewiness. 37107519 7 83 theme solid-state 1075:1085 arg1 fermentation 1087:1098 the mixed solid-state fermentation 1065:1098 the mixed solid-state fermentation 1065:1098 The above results pointed out that the mixed solid-state fermentation contributed to alteration of the SDF structure. 37107519 1 84 from fiber 210:214 arg1 SDFs 181:184 SDFs 181:184 SDFs 181:184 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 84 from fiber 210:214 arg1 fibers 173:178 soluble dietary fibers 157:178 soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) 157:245 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 8 85 theme U-SDF 1308:1312 arg1 times 1285:1289 about six times 1275:1289 about six times 1275:1289 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 8 85 theme U-SDF 1308:1312 arg1 times 1299:1303 two times 1295:1303 two times of U-SDF 1295:1312 Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. 37107519 1 86 theme solid-state 256:266 arg1 M-SDF 282:286 M-SDF 282:286 M-SDF 282:286 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 1 86 theme solid-state 256:266 arg1 fermentation 268:279 mixed solid-state fermentation 250:279 mixed solid-state fermentation (M-SDF) 250:287 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 37107519 9 87 dep highest 1387:1393 arg1 g/g 1419:1421 12.88 ± 0.15 g/g 1406:1421 12.88 ± 0.15 g/g 1406:1421 Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. 37107519 12 88 theme functional 1883:1892 arg1 food 1894:1897 functional food 1883:1897 functional food 1883:1897 In general, M-SDF displayed much excellent structural and functional properties, which could be utilized to develop functional food. 37107519 3 89 theme scanning 611:618 arg1 microscopy 629:638 scanning electron microscopy 611:638 scanning electron microscopy 611:638 The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. 37107519 4 90 theme microscopy 724:733 arg1 analysis 694:701 The analysis 690:701 The analysis of scanning electron microscopy 690:733 The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. 37107519 1 91 theme insoluble 192:200 arg1 fiber 210:214 insoluble dietary fiber 192:214 insoluble dietary fiber of navel orange peel (NOP-IDF) 192:245 The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. 35788050 12 0 theme specific 1777:1784 arg1 genes 1790:1794 specific RSV genes 1777:1794 specific RSV genes 1777:1794 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 4 1 theme chain 541:545 arg1 reaction 547:554 Reverse transcription-polymerase chain reaction 508:554 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) 500:563 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 4 1 theme chain 541:545 arg1 RT-PCR 557:562 RT-PCR 557:562 RT-PCR 557:562 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 7 2 theme Basic 1034:1038 arg1 BLAST 1069:1073 BLAST 1069:1073 BLAST 1069:1073 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 7 2 theme Basic 1034:1038 arg1 Tool 1063:1066 the Basic Local Alignment Search Tool 1030:1066 the Basic Local Alignment Search Tool (BLAST) 1030:1074 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 12 3 from sequences 1887:1895 arg1 gene 1906:1909 the F gene 1900:1909 the F gene 1900:1909 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 1 4 theme heavy 212:216 arg1 burden 226:231 a heavy disease burden 210:231 a heavy disease burden 210:231 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 14 5 theme acid 2090:2093 arg1 similarity 2095:2104 amino acid similarity 2084:2104 amino acid similarity 2084:2104 A high nucleotide identity and amino acid similarity were observed between the reference strain and the obtained strains, as well as among the sequences of the obtained isotypes. 35788050 10 6 theme sequences 1542:1550 arg1 total 1513:1517 A total 1511:1517 A total of 17 RSV whole genome sequences 1511:1550 A total of 17 RSV whole genome sequences were obtained, 10 of which were genotype ON1 and seven were genotype BA11. 35788050 12 7 theme N- 1857:1858 arg1 sequences 1887:1895 the N- and O-linked glycosylation sequences 1853:1895 the N- and O-linked glycosylation sequences in the F gene 1853:1909 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 10 8 theme whole 1529:1533 arg1 sequences 1542:1550 17 RSV whole genome sequences 1522:1550 17 RSV whole genome sequences 1522:1550 A total of 17 RSV whole genome sequences were obtained, 10 of which were genotype ON1 and seven were genotype BA11. 35788050 15 9 theme protein 2312:2318 arg1 site 2282:2285 the antigen site 2270:2285 the antigen site 2270:2285 Certain amino acid mutations occur at the antigen site and the epitope of the F protein. 35788050 15 9 theme protein 2312:2318 arg1 epitope 2295:2301 the epitope 2291:2301 the epitope of the F protein 2291:2318 Certain amino acid mutations occur at the antigen site and the epitope of the F protein. 35788050 15 9 theme protein 2312:2318 arg1 protein 2312:2318 the F protein 2306:2318 the F protein 2306:2318 Certain amino acid mutations occur at the antigen site and the epitope of the F protein. 35788050 1 10 theme main 149:152 arg1 causes 154:159 the main causes 145:159 the main causes of acute respiratory infections (ARI) leading to a heavy disease burden 145:231 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 2 11 from Province 292:299 arg1 limited 262:268 limited 262:268 limited 262:268 Reports on RSV in China are limited, especially in Fujian Province, and RSV whole-genome sequences in Fujian Province are not reported. 35788050 8 12 theme nucleotide 1136:1145 arg1 % 1167:1167 95.3%-99.8% 1157:1167 95.3%-99.8% 1157:1167 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 12 theme nucleotide 1136:1145 arg1 identity 1147:1154 high nucleotide identity 1131:1154 high nucleotide identity (95.3%-99.8%) 1131:1168 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 14 13 theme nucleotide 2060:2069 arg1 identity 2071:2078 A high nucleotide identity 2053:2078 A high nucleotide identity 2053:2078 A high nucleotide identity and amino acid similarity were observed between the reference strain and the obtained strains, as well as among the sequences of the obtained isotypes. 35788050 5 14 theme acid 807:810 arg1 mutations 812:820 any amino acid mutations 797:820 any amino acid mutations 797:820 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. 35788050 6 15 theme gene 889:892 arg1 sequences 894:902 53 G gene sequences 884:902 53 G gene sequences 884:902 RESULTS A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. 35788050 4 16 used used 569:572 arg2 METHODS 500:506 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) 500:563 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) 500:563 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 1 17 theme respiratory 170:180 arg1 ARI 194:196 ARI 194:196 ARI 194:196 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 1 17 theme respiratory 170:180 arg1 infections 182:191 acute respiratory infections 164:191 acute respiratory infections (ARI) leading to a heavy disease burden 164:231 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 8 18 theme nucleotide 1266:1275 arg1 identity 1277:1284  - 99.6% nucleotide identity 1257:1284  - 99.6% nucleotide identity 1257:1284 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 19 theme % 1161:1161 arg1 % 1167:1167 95.3%-99.8% 1157:1167 95.3%-99.8% 1157:1167 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 19 theme % 1161:1161 arg1 identity 1147:1154 high nucleotide identity 1131:1154 high nucleotide identity (95.3%-99.8%) 1131:1168 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 10 20 theme genotype 1584:1591 arg1 ON1 1593:1595 genotype ON1 1584:1595 genotype ON1 1584:1595 A total of 17 RSV whole genome sequences were obtained, 10 of which were genotype ON1 and seven were genotype BA11. 35788050 8 21 theme ON1 1113:1115 arg1 sequences 1117:1125 The 40 genotype ON1 sequences 1097:1125 The 40 genotype ON1 sequences 1097:1125 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 12 22 theme selection 1819:1827 arg1 rates 1829:1833 high positive selection rates 1805:1833 high positive selection rates for the gene 1805:1846 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 10 23 theme which 1573:1577 arg1 which 1573:1577 which 1573:1577 which 1573:1577 A total of 17 RSV whole genome sequences were obtained, 10 of which were genotype ON1 and seven were genotype BA11. 35788050 10 23 theme which 1573:1577 arg1 10 1567:1568 10 1567:1568 10 1567:1568 A total of 17 RSV whole genome sequences were obtained, 10 of which were genotype ON1 and seven were genotype BA11. 35788050 2 24 from Reports 234:240 arg1 China 252:256 China 252:256 China 252:256 Reports on RSV in China are limited, especially in Fujian Province, and RSV whole-genome sequences in Fujian Province are not reported. 35788050 2 24 from Reports 234:240 arg1 RSV 245:247 RSV 245:247 RSV 245:247 Reports on RSV in China are limited, especially in Fujian Province, and RSV whole-genome sequences in Fujian Province are not reported. 35788050 6 25 theme cases 858:862 arg1 total 833:837 A total 831:837 RESULTS A total of 72 RSV-positive cases 823:862 RESULTS A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. 35788050 7 26 theme Alignment 1046:1054 arg1 BLAST 1069:1073 BLAST 1069:1073 BLAST 1069:1073 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 7 26 theme Alignment 1046:1054 arg1 Tool 1063:1066 the Basic Local Alignment Search Tool 1030:1066 the Basic Local Alignment Search Tool (BLAST) 1030:1074 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 4 27 theme positive 656:663 arg1 samples 665:671 the positive samples 652:671 the positive samples 652:671 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 1 28 theme BACKGROUND 90:99 arg1 RSV 130:132 RSV 130:132 RSV 130:132 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 1 28 theme BACKGROUND 90:99 arg1 virus 123:127 BACKGROUND Respiratory syncytial virus 90:127 BACKGROUND Respiratory syncytial virus (RSV) 90:133 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 0 29 from China 83:87 arg1 analysis 7:14 Genome analysis 0:14 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 0:88 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 35788050 4 30 theme gene 615:618 arg1 fragments 637:645 gene and whole-genome fragments 615:645 fragments 637:645 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 8 31 dep similarity 1315:1324 arg1 % 1302:1302 % 1302:1302 % 1302:1302 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 6 32 theme chain 935:939 arg1 reaction 941:948 polymerase chain reaction 924:948 polymerase chain reaction (PCR) amplification 924:968 RESULTS A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. 35788050 6 32 theme chain 935:939 arg1 PCR 951:953 PCR 951:953 PCR 951:953 RESULTS A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. 35788050 8 33 theme acid 1310:1313 arg1 similarity 1315:1324 94.8% - 99.7% amino acid similarity 1290:1324 94.8% - 99.7% amino acid similarity 1290:1324 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 11 34 located found 1661:1665 arg2 mutations 1646:1654 Certain amino acid mutations 1627:1654 Certain amino acid mutations 1627:1654 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 11 34 located found 1661:1665 arg1 site 1682:1685 antigen site 1674:1685 antigen site 1674:1685 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 11 34 located found 1661:1665 arg1 protein 1717:1723 the fusion (F) protein 1702:1723 the fusion (F) protein 1702:1723 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 4 35 theme whole-genome 624:635 arg1 fragments 637:645 gene and whole-genome fragments 615:645 fragments 637:645 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 5 36 theme nucleotide 703:712 arg1 analyses 738:745 nucleotide and amino acid homology analyses 703:745 analyses 738:745 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. 35788050 15 37 theme amino 2240:2244 arg1 mutations 2251:2259 Certain amino acid mutations 2232:2259 Certain amino acid mutations 2232:2259 Certain amino acid mutations occur at the antigen site and the epitope of the F protein. 35788050 9 38 theme prototype 1347:1355 arg1 JN257693 1358:1365 the ON1 prototype (JN257693) and BA11 prototype 1339:1385 JN257693 1358:1365 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 9 38 theme prototype 1347:1355 arg1 AY333364 1388:1395 AY333364 1388:1395 AY333364 1388:1395 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 2 39 from limited 262:268 arg1 Province 292:299 Province 292:299 Province 292:299 Reports on RSV in China are limited, especially in Fujian Province, and RSV whole-genome sequences in Fujian Province are not reported. 35788050 8 40 theme % 1201:1201 arg1 % 1206:1206 92.5%-100% 1197:1206 92.5%-100% 1197:1206 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 40 theme % 1201:1201 arg1 similarity 1185:1194 amino acid similarity 1174:1194 amino acid similarity (92.5%-100%) 1174:1207 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 0 41 from virus 47:51 arg1 Southeast 73:81 Southeast 73:81 Southeast 73:81 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 35788050 0 41 from virus 47:51 arg1 China 83:87 China 83:87 China 83:87 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 35788050 11 42 theme antigen 1674:1680 arg1 site 1682:1685 antigen site 1674:1685 antigen site 1674:1685 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 11 42 theme antigen 1674:1680 arg1 protein 1717:1723 the fusion (F) protein 1702:1723 the fusion (F) protein 1702:1723 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 7 43 theme NCBI 1083:1086 arg1 website 1088:1094 the NCBI website 1079:1094 the NCBI website 1079:1094 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 0 44 theme syncytial 37:45 arg1 virus 47:51 human respiratory syncytial virus 19:51 human respiratory syncytial virus in Fujian Province, Southeast China 19:87 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 35788050 13 45 from July 1955:1958 arg1 CONCLUSIONS 1938:1948 CONCLUSIONS 1938:1948 CONCLUSIONS From July 2018 to January 2020 1938:1979 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 13 45 from July 1955:1958 arg1 genotypes 2023:2031 the most prevalent RSV genotypes 2000:2031 the most prevalent RSV genotypes in Fujian Province 2000:2050 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 13 45 from July 1955:1958 arg1 ON1 1982:1984 ON1 1982:1984 ON1 1982:1984 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 13 45 from July 1955:1958 arg1 BA11 1990:1993 BA11 1990:1993 BA11 1990:1993 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 0 46 theme Genome 0:5 arg1 analysis 7:14 Genome analysis 0:14 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 0:88 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 35788050 5 47 theme virus 754:758 arg1 sequences 760:768 the virus sequences 750:768 the virus sequences 750:768 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. 35788050 10 48 theme RSV 1525:1527 arg1 sequences 1542:1550 17 RSV whole genome sequences 1522:1550 17 RSV whole genome sequences 1522:1550 A total of 17 RSV whole genome sequences were obtained, 10 of which were genotype ON1 and seven were genotype BA11. 35788050 1 49 theme Respiratory 101:111 arg1 RSV 130:132 RSV 130:132 RSV 130:132 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 1 49 theme Respiratory 101:111 arg1 virus 123:127 BACKGROUND Respiratory syncytial virus 90:127 BACKGROUND Respiratory syncytial virus (RSV) 90:133 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 8 50 theme acid 1180:1183 arg1 % 1206:1206 92.5%-100% 1197:1206 92.5%-100% 1197:1206 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 50 theme acid 1180:1183 arg1 similarity 1185:1194 amino acid similarity 1174:1194 amino acid similarity (92.5%-100%) 1174:1207 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 51 theme BA11 1225:1228 arg1 % 1256:1256 the 13 BA11 genotype sequenceshad 97.3% 1218:1256 the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity 1218:1324 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 5 52 theme amino 718:722 arg1 analyses 738:745 nucleotide and amino acid homology analyses 703:745 analyses 738:745 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. 35788050 0 53 theme respiratory 25:35 arg1 virus 47:51 human respiratory syncytial virus 19:51 human respiratory syncytial virus in Fujian Province, Southeast China 19:87 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 35788050 2 54 from sequences 323:331 arg1 Province 343:350 Province 343:350 Province 343:350 Reports on RSV in China are limited, especially in Fujian Province, and RSV whole-genome sequences in Fujian Province are not reported. 35788050 8 55 theme sequenceshad 1239:1250 arg1 % 1256:1256 the 13 BA11 genotype sequenceshad 97.3% 1218:1256 the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity 1218:1324 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 3 56 theme RSV 429:431 arg1 characteristics 410:424 the genomic characteristics 398:424 the genomic characteristics of RSV 398:431 This study aimed to explore the genomic characteristics of RSV to provide evidence for the development of vaccines and medicines. 35788050 5 57 theme homology 729:736 arg1 analyses 738:745 nucleotide and amino acid homology analyses 703:745 analyses 738:745 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. 35788050 14 58 theme isotypes 2222:2229 arg1 sequences 2196:2204 the sequences 2192:2204 the sequences of the obtained isotypes 2192:2229 A high nucleotide identity and amino acid similarity were observed between the reference strain and the obtained strains, as well as among the sequences of the obtained isotypes. 35788050 9 59 theme obtained 1403:1410 arg1 sequences 1412:1420 the obtained sequences 1399:1420 the obtained sequences 1399:1420 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 11 60 theme G 1740:1740 arg1 protein 1742:1748 the G protein 1736:1748 the G protein 1736:1748 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 14 61 theme obtained 2157:2164 arg1 strains 2166:2172 the obtained strains 2153:2172 the obtained strains 2153:2172 A high nucleotide identity and amino acid similarity were observed between the reference strain and the obtained strains, as well as among the sequences of the obtained isotypes. 35788050 12 62 theme RSV 1786:1788 arg1 genes 1790:1794 specific RSV genes 1777:1794 specific RSV genes 1777:1794 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 8 63 theme % 1264:1264 arg1 identity 1277:1284  - 99.6% nucleotide identity 1257:1284  - 99.6% nucleotide identity 1257:1284 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 2 64 theme RSV 306:308 arg1 sequences 323:331 RSV whole-genome sequences 306:331 RSV whole-genome sequences in Fujian Province 306:350 Reports on RSV in China are limited, especially in Fujian Province, and RSV whole-genome sequences in Fujian Province are not reported. 35788050 7 65 theme Local 1040:1044 arg1 BLAST 1069:1073 BLAST 1069:1073 BLAST 1069:1073 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 7 65 theme Local 1040:1044 arg1 Tool 1063:1066 the Basic Local Alignment Search Tool 1030:1066 the Basic Local Alignment Search Tool (BLAST) 1030:1074 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 6 66 theme RSV-positive 845:856 arg1 cases 858:862 72 RSV-positive cases 842:862 72 RSV-positive cases 842:862 RESULTS A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. 35788050 9 67 theme nucleotide 1429:1438 arg1 insertions 1440:1449 no nucleotide insertions 1426:1449 no nucleotide insertions 1426:1449 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 6 68 dep RESULTS 823:829 arg1 total 833:837 A total 831:837 RESULTS A total of 72 RSV-positive cases 823:862 RESULTS A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. 35788050 11 69 theme acid 1641:1644 arg1 mutations 1646:1654 Certain amino acid mutations 1627:1654 Certain amino acid mutations 1627:1654 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 4 70 theme transcription-polymerase 516:539 arg1 reaction 547:554 Reverse transcription-polymerase chain reaction 508:554 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) 500:563 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 4 70 theme transcription-polymerase 516:539 arg1 RT-PCR 557:562 RT-PCR 557:562 RT-PCR 557:562 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 3 71 theme vaccines 476:483 arg1 development 461:471 the development 457:471 the development of vaccines and medicines 457:497 This study aimed to explore the genomic characteristics of RSV to provide evidence for the development of vaccines and medicines. 35788050 1 72 theme disease 218:224 arg1 burden 226:231 a heavy disease burden 210:231 a heavy disease burden 210:231 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 12 73 theme high 1805:1808 arg1 rates 1829:1833 high positive selection rates 1805:1833 high positive selection rates for the gene 1805:1846 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 11 74 theme Certain 1627:1633 arg1 mutations 1646:1654 Certain amino acid mutations 1627:1654 Certain amino acid mutations 1627:1654 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 14 75 theme amino 2084:2088 arg1 similarity 2095:2104 amino acid similarity 2084:2104 amino acid similarity 2084:2104 A high nucleotide identity and amino acid similarity were observed between the reference strain and the obtained strains, as well as among the sequences of the obtained isotypes. 35788050 10 76 theme genome 1535:1540 arg1 sequences 1542:1550 17 RSV whole genome sequences 1522:1550 17 RSV whole genome sequences 1522:1550 A total of 17 RSV whole genome sequences were obtained, 10 of which were genotype ON1 and seven were genotype BA11. 35788050 1 77 theme causes 154:159 arg1 causes 154:159 the main causes 145:159 the main causes of acute respiratory infections (ARI) leading to a heavy disease burden 145:231 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 1 77 theme causes 154:159 arg1 one 138:140 one 138:140 one 138:140 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 0 78 theme virus 47:51 arg1 analysis 7:14 Genome analysis 0:14 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 0:88 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 35788050 9 79 theme high 1476:1479 arg1 similarity 1481:1490 high similarity 1476:1490 high similarity among the samples 1476:1508 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 12 80 theme O-linked 1864:1871 arg1 glycosylation 1873:1885 O-linked glycosylation 1864:1885 O-linked glycosylation 1864:1885 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 12 81 theme genes 1790:1794 arg1 analyses 1765:1772 Glycosylation analyses 1751:1772 Glycosylation analyses of specific RSV genes 1751:1794 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 5 82 theme amino 801:805 arg1 mutations 812:820 any amino acid mutations 797:820 any amino acid mutations 797:820 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. 35788050 13 83 dep July 1955:1958 arg1 to 1965:1966 to 1965:1966 to 1965:1966 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 13 83 dep July 1955:1958 arg1 January 1968:1974 January 1968:1974 January 1968:1974 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 8 84 contain had 1127:1129 arg1 sequences 1117:1125 The 40 genotype ON1 sequences 1097:1125 The 40 genotype ON1 sequences 1097:1125 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 84 contain had 1127:1129 arg2 similarity 1185:1194 amino acid similarity 1174:1194 amino acid similarity (92.5%-100%) 1174:1207 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 84 contain had 1127:1129 arg2 % 1206:1206 92.5%-100% 1197:1206 92.5%-100% 1197:1206 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 84 contain had 1127:1129 arg2 identity 1147:1154 high nucleotide identity 1131:1154 high nucleotide identity (95.3%-99.8%) 1131:1168 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 84 contain had 1127:1129 arg2 % 1167:1167 95.3%-99.8% 1157:1167 95.3%-99.8% 1157:1167 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 85 theme high 1131:1134 arg1 % 1167:1167 95.3%-99.8% 1157:1167 95.3%-99.8% 1157:1167 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 85 theme high 1131:1134 arg1 identity 1147:1154 high nucleotide identity 1131:1154 high nucleotide identity (95.3%-99.8%) 1131:1168 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 7 86 theme BA11 983:986 arg1 dominant 1015:1022 dominant 1015:1022 dominant 1015:1022 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 7 86 theme BA11 983:986 arg1 genotypes 988:996 The ON1 and BA11 genotypes 971:996 The ON1 and BA11 genotypes 971:996 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 14 87 theme high 2055:2058 arg1 identity 2071:2078 A high nucleotide identity 2053:2078 A high nucleotide identity 2053:2078 A high nucleotide identity and amino acid similarity were observed between the reference strain and the obtained strains, as well as among the sequences of the obtained isotypes. 35788050 3 88 theme medicines 489:497 arg1 development 461:471 the development 457:471 the development of vaccines and medicines 457:497 This study aimed to explore the genomic characteristics of RSV to provide evidence for the development of vaccines and medicines. 35788050 15 89 theme F 2310:2310 arg1 protein 2312:2318 the F protein 2306:2318 the F protein 2306:2318 Certain amino acid mutations occur at the antigen site and the epitope of the F protein. 35788050 1 90 theme acute 164:168 arg1 ARI 194:196 ARI 194:196 ARI 194:196 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 1 90 theme acute 164:168 arg1 infections 182:191 acute respiratory infections 164:191 acute respiratory infections (ARI) leading to a heavy disease burden 164:231 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 6 91 theme 53 G 884:887 arg1 sequences 894:902 53 G gene sequences 884:902 53 G gene sequences 884:902 RESULTS A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. 35788050 7 92 theme ON1 975:977 arg1 dominant 1015:1022 dominant 1015:1022 dominant 1015:1022 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 7 92 theme ON1 975:977 arg1 genotypes 988:996 The ON1 and BA11 genotypes 971:996 The ON1 and BA11 genotypes 971:996 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 11 93 theme F 1714:1714 arg1 protein 1717:1723 the fusion (F) protein 1702:1723 the fusion (F) protein 1702:1723 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 1 94 theme infections 182:191 arg1 causes 154:159 the main causes 145:159 the main causes of acute respiratory infections (ARI) leading to a heavy disease burden 145:231 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 8 95 theme 94.8 1290:1293 arg1 % 1294:1294 % 1294:1294 % 1294:1294 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 9 96 contain had 1422:1424 arg2 insertions 1440:1449 no nucleotide insertions 1426:1449 no nucleotide insertions 1426:1449 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 9 96 contain had 1422:1424 arg1 sequences 1412:1420 the obtained sequences 1399:1420 the obtained sequences 1399:1420 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 9 96 contain had 1422:1424 arg2 deletions 1454:1462 deletions 1454:1462 deletions 1454:1462 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 11 97 theme fusion 1706:1711 arg1 protein 1717:1723 the fusion (F) protein 1702:1723 the fusion (F) protein 1702:1723 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 1 98 theme syncytial 113:121 arg1 RSV 130:132 RSV 130:132 RSV 130:132 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 1 98 theme syncytial 113:121 arg1 virus 123:127 BACKGROUND Respiratory syncytial virus 90:127 BACKGROUND Respiratory syncytial virus (RSV) 90:133 BACKGROUND Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. 35788050 8 99 theme genotype 1104:1111 arg1 sequences 1117:1125 The 40 genotype ON1 sequences 1097:1125 The 40 genotype ON1 sequences 1097:1125 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 100 theme  - 99.7 1295:1301 arg1 % 1294:1294 % 1294:1294 % 1294:1294 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 12 101 theme positive 1810:1817 arg1 rates 1829:1833 high positive selection rates 1805:1833 high positive selection rates for the gene 1805:1846 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 10 102 theme genotype 1612:1619 arg1 BA11 1621:1624 genotype BA11 1612:1624 genotype BA11 1612:1624 A total of 17 RSV whole genome sequences were obtained, 10 of which were genotype ON1 and seven were genotype BA11. 35788050 8 103 dep % 1256:1256 arg1 identity 1277:1284  - 99.6% nucleotide identity 1257:1284  - 99.6% nucleotide identity 1257:1284 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 103 dep % 1256:1256 arg1 similarity 1315:1324 94.8% - 99.7% amino acid similarity 1290:1324 94.8% - 99.7% amino acid similarity 1290:1324 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 104 theme amino 1304:1308 arg1 similarity 1315:1324 94.8% - 99.7% amino acid similarity 1290:1324 94.8% - 99.7% amino acid similarity 1290:1324 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 11 105 theme protein 1717:1723 arg1 site 1682:1685 antigen site 1674:1685 antigen site 1674:1685 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 11 105 theme protein 1717:1723 arg1 protein 1717:1723 the fusion (F) protein 1702:1723 the fusion (F) protein 1702:1723 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 5 106 theme sequences 760:768 arg1 evolution 682:690 Genetic evolution 674:690 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences 674:768 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. 35788050 5 106 theme sequences 760:768 arg1 analyses 738:745 nucleotide and amino acid homology analyses 703:745 analyses 738:745 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. 35788050 6 107 theme reaction 941:948 arg1 amplification 956:968 polymerase chain reaction (PCR) amplification 924:968 polymerase chain reaction (PCR) amplification 924:968 RESULTS A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. 35788050 8 108 theme amino 1174:1178 arg1 % 1206:1206 92.5%-100% 1197:1206 92.5%-100% 1197:1206 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 8 108 theme amino 1174:1178 arg1 similarity 1185:1194 amino acid similarity 1174:1194 amino acid similarity (92.5%-100%) 1174:1207 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 9 109 theme ON1 1343:1345 arg1 JN257693 1358:1365 the ON1 prototype (JN257693) and BA11 prototype 1339:1385 JN257693 1358:1365 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 9 109 theme ON1 1343:1345 arg1 AY333364 1388:1395 AY333364 1388:1395 AY333364 1388:1395 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 6 110 theme polymerase 924:933 arg1 reaction 941:948 polymerase chain reaction 924:948 polymerase chain reaction (PCR) amplification 924:968 RESULTS A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. 35788050 6 110 theme polymerase 924:933 arg1 PCR 951:953 PCR 951:953 PCR 951:953 RESULTS A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. 35788050 0 111 from analysis 7:14 arg1 Southeast 73:81 Southeast 73:81 Southeast 73:81 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 35788050 0 111 from analysis 7:14 arg1 China 83:87 China 83:87 China 83:87 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 35788050 15 112 theme acid 2246:2249 arg1 mutations 2251:2259 Certain amino acid mutations 2232:2259 Certain amino acid mutations 2232:2259 Certain amino acid mutations occur at the antigen site and the epitope of the F protein. 35788050 13 113 theme prevalent 2009:2017 arg1 genotypes 2023:2031 the most prevalent RSV genotypes 2000:2031 the most prevalent RSV genotypes in Fujian Province 2000:2050 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 13 113 theme prevalent 2009:2017 arg1 CONCLUSIONS 1938:1948 CONCLUSIONS 1938:1948 CONCLUSIONS From July 2018 to January 2020 1938:1979 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 5 114 theme Genetic 674:680 arg1 evolution 682:690 Genetic evolution 674:690 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences 674:768 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. 35788050 4 115 dep METHODS 500:506 arg1 reaction 547:554 Reverse transcription-polymerase chain reaction 508:554 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) 500:563 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 4 115 dep METHODS 500:506 arg1 RT-PCR 557:562 RT-PCR 557:562 RT-PCR 557:562 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 13 116 theme RSV 2019:2021 arg1 genotypes 2023:2031 the most prevalent RSV genotypes 2000:2031 the most prevalent RSV genotypes in Fujian Province 2000:2050 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 13 116 theme RSV 2019:2021 arg1 CONCLUSIONS 1938:1948 CONCLUSIONS 1938:1948 CONCLUSIONS From July 2018 to January 2020 1938:1979 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 9 117 theme BA11 1372:1375 arg1 prototype 1377:1385 the ON1 prototype (JN257693) and BA11 prototype 1339:1385 prototype 1377:1385 Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. 35788050 15 118 theme Certain 2232:2238 arg1 mutations 2251:2259 Certain amino acid mutations 2232:2259 Certain amino acid mutations 2232:2259 Certain amino acid mutations occur at the antigen site and the epitope of the F protein. 35788050 2 119 theme whole-genome 310:321 arg1 sequences 323:331 RSV whole-genome sequences 306:331 RSV whole-genome sequences in Fujian Province 306:350 Reports on RSV in China are limited, especially in Fujian Province, and RSV whole-genome sequences in Fujian Province are not reported. 35788050 0 120 theme human 19:23 arg1 virus 47:51 human respiratory syncytial virus 19:51 human respiratory syncytial virus in Fujian Province, Southeast China 19:87 Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China. 35788050 8 121 dep % 1302:1302 arg1 % 1294:1294 % 1294:1294 % 1294:1294 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 4 122 from samples 665:671 arg1 fragments 637:645 gene and whole-genome fragments 615:645 fragments 637:645 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 8 123 dep had 1127:1129 arg1 whereas 1210:1216 whereas 1210:1216 whereas 1210:1216 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 4 124 theme Reverse 508:514 arg1 reaction 547:554 Reverse transcription-polymerase chain reaction 508:554 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) 500:563 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 4 124 theme Reverse 508:514 arg1 RT-PCR 557:562 RT-PCR 557:562 RT-PCR 557:562 METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. 35788050 3 125 theme genomic 402:408 arg1 characteristics 410:424 the genomic characteristics 398:424 the genomic characteristics of RSV 398:431 This study aimed to explore the genomic characteristics of RSV to provide evidence for the development of vaccines and medicines. 35788050 7 126 theme Search 1056:1061 arg1 BLAST 1069:1073 BLAST 1069:1073 BLAST 1069:1073 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 7 126 theme Search 1056:1061 arg1 Tool 1063:1066 the Basic Local Alignment Search Tool 1030:1066 the Basic Local Alignment Search Tool (BLAST) 1030:1074 The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. 35788050 12 127 theme F 1904:1904 arg1 gene 1906:1909 the F gene 1900:1909 the F gene 1900:1909 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 13 128 from genotypes 2023:2031 arg1 Province 2043:2050 Province 2043:2050 Province 2043:2050 CONCLUSIONS From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. 35788050 5 129 theme acid 724:727 arg1 analyses 738:745 nucleotide and amino acid homology analyses 703:745 analyses 738:745 Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. 35788050 12 130 theme Glycosylation 1751:1763 arg1 analyses 1765:1772 Glycosylation analyses 1751:1772 Glycosylation analyses of specific RSV genes 1751:1794 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 12 131 link O-linked 1864:1871 arg1 glycosylation 1873:1885 O-linked glycosylation 1864:1885 O-linked glycosylation 1864:1885 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 8 132 theme genotype 1230:1237 arg1 % 1256:1256 the 13 BA11 genotype sequenceshad 97.3% 1218:1256 the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity 1218:1324 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35788050 11 133 theme amino 1635:1639 arg1 mutations 1646:1654 Certain amino acid mutations 1627:1654 Certain amino acid mutations 1627:1654 Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. 35788050 14 134 theme obtained 2213:2220 arg1 isotypes 2222:2229 the obtained isotypes 2209:2229 the obtained isotypes 2209:2229 A high nucleotide identity and amino acid similarity were observed between the reference strain and the obtained strains, as well as among the sequences of the obtained isotypes. 35788050 12 135 theme glycosylation 1873:1885 arg1 sequences 1887:1895 the N- and O-linked glycosylation sequences 1853:1895 the N- and O-linked glycosylation sequences in the F gene 1853:1909 Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. 35788050 14 136 theme reference 2132:2140 arg1 strain 2142:2147 the reference strain 2128:2147 the reference strain 2128:2147 A high nucleotide identity and amino acid similarity were observed between the reference strain and the obtained strains, as well as among the sequences of the obtained isotypes. 35788050 15 137 theme antigen 2274:2280 arg1 site 2282:2285 the antigen site 2270:2285 the antigen site 2270:2285 Certain amino acid mutations occur at the antigen site and the epitope of the F protein. 35788050 15 137 theme antigen 2274:2280 arg1 protein 2312:2318 the F protein 2306:2318 the F protein 2306:2318 Certain amino acid mutations occur at the antigen site and the epitope of the F protein. 35788050 8 138 theme  - 99.6 1257:1263 arg1 % 1264:1264 % 1264:1264 % 1264:1264 The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. 35296731 1 0 link O-linked 119:126 arg1 modification 209:220 a reversible post-translational modification 177:220 a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins 177:302 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 1 0 link O-linked 119:126 arg1 O-GlcNAcylation 157:171 O-GlcNAcylation 157:171 O-GlcNAcylation 157:171 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 1 0 link O-linked 119:126 arg1 β-N-acetylglucosaminylation 128:154 O-linked β-N-acetylglucosaminylation 119:154 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 119:172 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 7 1 theme plasma 1203:1208 arg1 membrane 1210:1217 the plasma membrane 1199:1217 the plasma membrane 1199:1217 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 9 2 dep cell 1717:1720 arg1 proliferation 1733:1745 proliferation 1733:1745 proliferation 1733:1745 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 9 2 dep cell 1717:1720 arg1 growth 1722:1727 growth 1722:1727 growth 1722:1727 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 7 3 theme 3-phosphate 1173:1183 arg1 production 1185:1194 increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production 1127:1194 increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane 1127:1217 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 4 4 theme cervical 659:666 arg1 cells 689:693 cervical cancer-derived CaSki cells 659:693 cervical cancer-derived CaSki cells 659:693 In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. 35296731 7 5 theme IGF-1-induced 1137:1149 arg1 production 1185:1194 increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production 1127:1194 increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane 1127:1217 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 1 6 theme cytosolic 258:266 arg1 proteins 295:302 cytosolic, nuclear and mitochondrial proteins 258:302 cytosolic, nuclear and mitochondrial proteins 258:302 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 4 7 theme CaSki 683:687 arg1 cells 689:693 cervical cancer-derived CaSki cells 659:693 cervical cancer-derived CaSki cells 659:693 In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. 35296731 5 8 theme Thiamet 771:777 arg1 G 779:779 Thiamet G 771:779 Thiamet G (an inhibitor of OGA) 771:801 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 7 9 theme CaSki 1251:1255 arg1 cells 1257:1261 CaSki cells 1251:1261 CaSki cells 1251:1261 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 1 10 theme nuclear 269:275 arg1 proteins 295:302 cytosolic, nuclear and mitochondrial proteins 258:302 cytosolic, nuclear and mitochondrial proteins 258:302 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 8 11 theme Akt 1316:1318 arg1 levels 1336:1341 protein O-GlcNAcylation and Akt phosphorylation levels 1288:1341 levels 1336:1341 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 6 12 theme IGF-1 985:989 arg1 autophosphorylation 1008:1026 IGF-1 receptor (IGF1R) autophosphorylation 985:1026 IGF-1 receptor (IGF1R) autophosphorylation 985:1026 Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. 35296731 5 13 theme pharmacological 713:727 arg1 enhancement 729:739 pharmacological enhancement 713:739 pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) 713:862 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 5 14 dep G 779:779 arg1 inhibitor 785:793 an inhibitor 782:793 an inhibitor of OGA 782:800 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 8 15 theme healthy 1400:1406 arg1 tissues 1415:1421 healthy cervix tissues 1400:1421 healthy cervix tissues 1400:1421 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 9 16 theme IGF1R/ 1621:1626 arg1 PI-3K 1660:1664 PI-3K 1660:1664 PI-3K 1660:1664 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 9 16 theme IGF1R/ 1621:1626 arg1 3-Kinase 1650:1657 IGF1R/ Phosphatidyl inositol 3-Kinase 1621:1657 IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling 1621:1679 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 6 17 theme tyrosine-phosphatase 1068:1087 arg1 activity 1092:1099 protein tyrosine-phosphatase 1B activity 1060:1099 protein tyrosine-phosphatase 1B activity 1060:1099 Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. 35296731 5 18 theme OGA 798:800 arg1 inhibitor 785:793 an inhibitor 782:793 an inhibitor of OGA 782:800 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 2 19 theme O-GlcNAcylation 305:319 arg1 level 321:325 O-GlcNAcylation level 305:325 O-GlcNAcylation level 305:325 O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. 35296731 9 20 theme inositol 1641:1648 arg1 PI-3K 1660:1664 PI-3K 1660:1664 PI-3K 1660:1664 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 9 20 theme inositol 1641:1648 arg1 3-Kinase 1650:1657 IGF1R/ Phosphatidyl inositol 3-Kinase 1621:1657 IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling 1621:1679 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 0 21 theme cancer 105:110 arg1 cells 112:116 cervical cancer cells 96:116 cervical cancer cells 96:116 Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells. 35296731 1 22 from modification 209:220 arg1 threonine 236:244 threonine 236:244 threonine 236:244 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 1 22 from modification 209:220 arg1 serine 225:230 serine 225:230 serine 225:230 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 3 23 theme protein 461:467 arg1 O-GlcNAcylation 469:483 protein O-GlcNAcylation 461:483 protein O-GlcNAcylation 461:483 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 0 24 theme Increased 0:8 arg1 O-GlcNAcylation 10:24 Increased O-GlcNAcylation 0:24 Increased O-GlcNAcylation 0:24 Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells. 35296731 1 25 theme O-linked 119:126 arg1 modification 209:220 a reversible post-translational modification 177:220 a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins 177:302 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 1 25 theme O-linked 119:126 arg1 O-GlcNAcylation 157:171 O-GlcNAcylation 157:171 O-GlcNAcylation 157:171 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 1 25 theme O-linked 119:126 arg1 β-N-acetylglucosaminylation 128:154 O-linked β-N-acetylglucosaminylation 119:154 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 119:172 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 4 26 theme present 574:580 arg1 study 582:586 the present study 570:586 the present study 570:586 In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. 35296731 8 27 theme O-GlcNAcylation 1479:1493 arg1 level 1495:1499 O-GlcNAcylation level 1479:1499 O-GlcNAcylation level 1479:1499 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 1 28 theme reversible 179:188 arg1 β-N-acetylglucosaminylation 128:154 O-linked β-N-acetylglucosaminylation 119:154 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 119:172 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 1 28 theme reversible 179:188 arg1 modification 209:220 a reversible post-translational modification 177:220 a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins 177:302 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 0 29 theme receptor/PhosphatidyI 41:61 arg1 pathway 85:91 IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway 35:91 IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells 35:116 Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells. 35296731 9 30 theme cancer 1710:1715 arg1 cell 1717:1720 cervical cancer cell growth and proliferation 1701:1745 cervical cancer cell growth and proliferation 1701:1745 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 6 31 theme activity 1092:1099 arg1 inhibition 1046:1055 inhibition 1046:1055 inhibition of protein tyrosine-phosphatase 1B activity 1046:1099 Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. 35296731 1 32 dep serine 225:230 arg1 residues 246:253 residues 246:253 residues 246:253 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 3 33 theme cell 522:525 arg1 cells 560:564 cervical cancer cells 544:564 cervical cancer cells 544:564 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 3 33 theme cell 522:525 arg1 types 527:531 numerous cancer cell types 506:531 numerous cancer cell types 506:531 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 7 34 theme Akt 1233:1235 arg1 activation 1237:1246 increased Akt activation 1223:1246 increased Akt activation in CaSki cells 1223:1261 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 3 35 theme numerous 506:513 arg1 cells 560:564 cervical cancer cells 544:564 cervical cancer cells 544:564 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 3 35 theme numerous 506:513 arg1 types 527:531 numerous cancer cell types 506:531 numerous cancer cell types 506:531 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 1 36 theme post-translational 190:207 arg1 β-N-acetylglucosaminylation 128:154 O-linked β-N-acetylglucosaminylation 119:154 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) 119:172 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 1 36 theme post-translational 190:207 arg1 modification 209:220 a reversible post-translational modification 177:220 a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins 177:302 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 3 37 theme cervical 544:551 arg1 cells 560:564 cervical cancer cells 544:564 cervical cancer cells 544:564 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 1 38 theme proteins 295:302 arg1 threonine 236:244 threonine 236:244 threonine 236:244 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 1 38 theme proteins 295:302 arg1 serine 225:230 serine 225:230 serine 225:230 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 6 39 theme increased 950:958 arg1 O-GlcNAcylation 960:974 increased O-GlcNAcylation 950:974 increased O-GlcNAcylation 950:974 Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. 35296731 4 40 theme protein 632:638 arg1 O-GlcNAcylation 640:654 increasing protein O-GlcNAcylation 621:654 increasing protein O-GlcNAcylation 621:654 In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. 35296731 2 41 from GlcNAc 382:387 arg1 proteins 392:399 proteins 392:399 proteins 392:399 O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. 35296731 2 42 theme O-GlcNAc 348:355 arg1 OGT 343:345 OGT 343:345 OGT (O-GlcNAc transferase) 343:368 O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. 35296731 2 42 theme O-GlcNAc 348:355 arg1 transferase 357:367 O-GlcNAc transferase 348:367 O-GlcNAc transferase 348:367 O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. 35296731 8 43 located observed 1462:1469 arg2 correlation 1446:1456 a highly positive correlation 1428:1456 a highly positive correlation 1428:1456 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 8 43 located observed 1462:1469 arg1 tissues 1535:1541 theses tissues 1528:1541 theses tissues 1528:1541 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 0 44 theme kinase/Akt 74:83 arg1 pathway 85:91 IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway 35:91 IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells 35:116 Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells. 35296731 8 45 theme phosphorylation 1320:1334 arg1 levels 1336:1341 protein O-GlcNAcylation and Akt phosphorylation levels 1288:1341 levels 1336:1341 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 7 46 theme phosphatidyl-Inositol 1151:1171 arg1 production 1185:1194 increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production 1127:1194 increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane 1127:1217 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 7 47 theme increased 1127:1135 arg1 production 1185:1194 increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production 1127:1194 increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane 1127:1217 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 6 48 theme IGF1R 1001:1005 arg1 autophosphorylation 1008:1026 IGF-1 receptor (IGF1R) autophosphorylation 985:1026 IGF-1 receptor (IGF1R) autophosphorylation 985:1026 Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. 35296731 5 49 theme CaSki 874:878 arg1 survival 915:922 survival 915:922 survival 915:922 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 5 49 theme CaSki 874:878 arg1 cells 880:884 CaSki cells proliferation, migration and survival 874:922 CaSki cells proliferation, migration and survival 874:922 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 5 49 theme CaSki 874:878 arg1 migration 901:909 migration 901:909 migration 901:909 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 5 49 theme CaSki 874:878 arg1 proliferation 886:898 proliferation 886:898 proliferation 886:898 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 8 50 theme protein 1288:1294 arg1 O-GlcNAcylation 1296:1310 protein O-GlcNAcylation and Akt phosphorylation levels 1288:1341 O-GlcNAcylation 1296:1310 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 6 51 theme receptor 991:998 arg1 autophosphorylation 1008:1026 IGF-1 receptor (IGF1R) autophosphorylation 985:1026 IGF-1 receptor (IGF1R) autophosphorylation 985:1026 Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. 35296731 4 52 theme cancer-derived 668:681 arg1 cells 689:693 cervical cancer-derived CaSki cells 659:693 cervical cancer-derived CaSki cells 659:693 In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. 35296731 5 53 theme protein 744:750 arg1 O-GlcNAcylation 752:766 protein O-GlcNAcylation 744:766 protein O-GlcNAcylation 744:766 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 6 54 theme 1B 1089:1090 arg1 activity 1092:1099 protein tyrosine-phosphatase 1B activity 1060:1099 protein tyrosine-phosphatase 1B activity 1060:1099 Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. 35296731 4 55 link cancer-derived 668:681 arg1 cells 689:693 cervical cancer-derived CaSki cells 659:693 cervical cancer-derived CaSki cells 659:693 In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. 35296731 0 56 theme cervical 96:103 arg1 cells 112:116 cervical cancer cells 96:116 cervical cancer cells 96:116 Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells. 35296731 8 57 theme human 1358:1362 arg1 samples 1380:1386 human cervical cancer samples 1358:1386 human cervical cancer samples 1358:1386 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 9 58 theme Phosphatidyl 1628:1639 arg1 PI-3K 1660:1664 PI-3K 1660:1664 PI-3K 1660:1664 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 9 58 theme Phosphatidyl 1628:1639 arg1 3-Kinase 1650:1657 IGF1R/ Phosphatidyl inositol 3-Kinase 1621:1657 IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling 1621:1679 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 6 59 theme protein 1060:1066 arg1 activity 1092:1099 protein tyrosine-phosphatase 1B activity 1060:1099 protein tyrosine-phosphatase 1B activity 1060:1099 Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. 35296731 8 60 theme cervix 1408:1413 arg1 tissues 1415:1421 healthy cervix tissues 1400:1421 healthy cervix tissues 1400:1421 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 9 61 theme 3-Kinase 1650:1657 arg1 signaling 1671:1679 IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling 1621:1679 IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling 1621:1679 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 5 62 theme O-GlcNAcylation 752:766 arg1 enhancement 729:739 pharmacological enhancement 713:739 pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) 713:862 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 7 63 from activation 1237:1246 arg1 cells 1257:1261 CaSki cells 1251:1261 CaSki cells 1251:1261 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 4 64 from effect 611:616 arg1 cells 689:693 cervical cancer-derived CaSki cells 659:693 cervical cancer-derived CaSki cells 659:693 In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. 35296731 3 65 located observed 494:501 arg2 level 452:456 Abnormal level 443:456 Abnormal level of protein O-GlcNAcylation 443:483 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 3 65 located observed 494:501 arg1 cells 560:564 cervical cancer cells 544:564 cervical cancer cells 544:564 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 3 65 located observed 494:501 arg1 types 527:531 numerous cancer cell types 506:531 numerous cancer cell types 506:531 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 0 66 from pathway 85:91 arg1 cells 112:116 cervical cancer cells 96:116 cervical cancer cells 96:116 Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells. 35296731 9 67 theme /Akt 1666:1669 arg1 signaling 1671:1679 IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling 1621:1679 IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling 1621:1679 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 8 68 theme positive 1437:1444 arg1 correlation 1446:1456 a highly positive correlation 1428:1456 a highly positive correlation 1428:1456 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 3 69 theme O-GlcNAcylation 469:483 arg1 level 452:456 Abnormal level 443:456 Abnormal level of protein O-GlcNAcylation 443:483 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 5 70 theme UDP-GlcNAc 835:844 arg1 substrate 846:854 UDP-GlcNAc substrate 835:854 UDP-GlcNAc substrate 835:854 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 0 71 theme IGF-1 35:39 arg1 pathway 85:91 IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway 35:91 IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells 35:116 Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells. 35296731 7 72 from production 1185:1194 arg1 cells 1257:1261 CaSki cells 1251:1261 CaSki cells 1251:1261 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 0 73 theme Inositol-3 63:72 arg1 pathway 85:91 IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway 35:91 IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells 35:116 Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells. 35296731 8 74 theme cancer 1373:1378 arg1 samples 1380:1386 human cervical cancer samples 1358:1386 human cervical cancer samples 1358:1386 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 9 75 theme cervical 1701:1708 arg1 cell 1717:1720 cervical cancer cell growth and proliferation 1701:1745 cervical cancer cell growth and proliferation 1701:1745 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 3 76 theme Abnormal 443:450 arg1 level 452:456 Abnormal level 443:456 Abnormal level of protein O-GlcNAcylation 443:483 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 7 77 theme increased 1223:1231 arg1 activation 1237:1246 increased Akt activation 1223:1246 increased Akt activation in CaSki cells 1223:1261 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 9 78 theme increased 1580:1588 arg1 O-GlcNAcylation 1590:1604 increased O-GlcNAcylation 1580:1604 increased O-GlcNAcylation 1580:1604 Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. 35296731 7 79 from membrane 1210:1217 arg1 production 1185:1194 increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production 1127:1194 increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane 1127:1217 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 7 79 from membrane 1210:1217 arg1 activation 1237:1246 increased Akt activation 1223:1246 increased Akt activation in CaSki cells 1223:1261 This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. 35296731 8 80 theme Akt 1505:1507 arg1 phosphorylation 1509:1523 Akt phosphorylation 1505:1523 Akt phosphorylation 1505:1523 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 4 81 theme increasing 621:630 arg1 O-GlcNAcylation 640:654 increasing protein O-GlcNAcylation 621:654 increasing protein O-GlcNAcylation 621:654 In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. 35296731 5 82 dep cells 880:884 arg1 survival 915:922 survival 915:922 survival 915:922 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 5 82 dep cells 880:884 arg1 cells 880:884 CaSki cells proliferation, migration and survival 874:922 CaSki cells proliferation, migration and survival 874:922 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 5 82 dep cells 880:884 arg1 migration 901:909 migration 901:909 migration 901:909 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 5 82 dep cells 880:884 arg1 proliferation 886:898 proliferation 886:898 proliferation 886:898 We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. 35296731 3 83 theme cancer 515:520 arg1 cells 560:564 cervical cancer cells 544:564 cervical cancer cells 544:564 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 3 83 theme cancer 515:520 arg1 types 527:531 numerous cancer cell types 506:531 numerous cancer cell types 506:531 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 35296731 1 84 theme mitochondrial 281:293 arg1 proteins 295:302 cytosolic, nuclear and mitochondrial proteins 258:302 cytosolic, nuclear and mitochondrial proteins 258:302 O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. 35296731 8 85 theme cervical 1364:1371 arg1 samples 1380:1386 human cervical cancer samples 1358:1386 human cervical cancer samples 1358:1386 Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. 35296731 4 86 theme O-GlcNAcylation 640:654 arg1 effect 611:616 the effect 607:616 the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells 607:693 In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. 35296731 3 87 theme cancer 553:558 arg1 cells 560:564 cervical cancer cells 544:564 cervical cancer cells 544:564 Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. 37141112 4 0 from target 578:583 arg1 DLBCL 644:648 ABC DLBCL 640:648 ABC DLBCL 640:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 5 1 theme OST-B 748:752 arg1 complex 755:761 the oligosaccharyltransferase-B (OST-B) complex 715:761 the oligosaccharyltransferase-B (OST-B) complex 715:761 Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. 37141112 7 2 theme inhibitors 1116:1125 arg1 development 1085:1095 the development 1081:1095 the development of selective OST-B inhibitors for the treatment of these aggressive cancers 1081:1171 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 1 3 theme B-cell 145:150 arg1 DLCBL 201:205 activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL 135:205 activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL 135:205 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 5 4 link N-linked 681:688 arg1 glycosylation 698:710 N-linked protein glycosylation 681:710 N-linked protein glycosylation 681:710 Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. 37141112 4 5 from DLBCL 644:648 arg1 indicator 601:609 an indicator 598:609 an indicator of proximal BCR signaling in ABC DLBCL 598:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 4 5 from DLBCL 644:648 arg1 target 578:583 a direct transcriptional target 553:583 a direct transcriptional target of NF-kB 553:592 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 4 5 from DLBCL 644:648 arg1 IRF4 547:550 IRF4 547:550 IRF4 547:550 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 4 6 theme IRF4 547:550 arg1 regulators 533:542 regulators 533:542 regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL 533:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 5 7 theme protein 690:696 arg1 glycosylation 698:710 N-linked protein glycosylation 681:710 N-linked protein glycosylation 681:710 Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. 37141112 7 8 theme selective 1100:1108 arg1 inhibitors 1116:1125 selective OST-B inhibitors 1100:1125 selective OST-B inhibitors for the treatment of these aggressive cancers 1100:1171 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 6 9 theme OST-B 788:792 arg1 inhibition 794:803 OST-B inhibition 788:803 OST-B inhibition of BCR glycosylation 788:824 OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. 37141112 5 10 theme IRF4 771:774 arg1 expression 776:785 IRF4 expression 771:785 IRF4 expression 771:785 Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. 37141112 4 11 theme direct 555:560 arg1 target 578:583 a direct transcriptional target 553:583 a direct transcriptional target of NF-kB 553:592 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 5 12 theme glycosylation 698:710 arg1 inactivation 665:676 inactivation 665:676 inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex 665:761 Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. 37141112 7 13 theme OST-B 1110:1114 arg1 inhibitors 1116:1125 selective OST-B inhibitors 1100:1125 selective OST-B inhibitors for the treatment of these aggressive cancers 1100:1171 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 0 14 link N-linked 10:17 arg1 Glycosylation 19:31 N-linked Glycosylation 10:31 N-linked Glycosylation 10:31 Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas. 37141112 2 15 theme chronic 318:324 arg1 signaling 333:341 chronic active signaling 318:341 chronic active signaling 318:341 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 2 16 theme kinase 375:380 arg1 activation 347:356 activation 347:356 activation of NF-kB and PI3 kinase 347:380 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 2 16 theme kinase 375:380 arg1 signaling 333:341 chronic active signaling 318:341 chronic active signaling 318:341 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 1 17 theme Diffuse 74:80 arg1 lymphoma 95:102 Diffuse large B-cell lymphoma 74:102 Diffuse large B-cell lymphoma (DLBCL) 74:110 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 1 17 theme Diffuse 74:80 arg1 DLBCL 105:109 DLBCL 105:109 DLBCL 105:109 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 4 18 from signaling 627:635 arg1 DLBCL 644:648 ABC DLBCL 640:648 ABC DLBCL 640:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 2 19 theme NF-kB 361:365 arg1 activation 347:356 activation 347:356 activation of NF-kB and PI3 kinase 347:380 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 2 19 theme NF-kB 361:365 arg1 signaling 333:341 chronic active signaling 318:341 chronic active signaling 318:341 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 4 20 from IRF4 547:550 arg1 DLBCL 644:648 ABC DLBCL 640:648 ABC DLBCL 640:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 3 21 from tumors 435:440 arg1 essential 413:421 essential 413:421 essential 413:421 Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase. 37141112 1 22 theme large 82:86 arg1 lymphoma 95:102 Diffuse large B-cell lymphoma 74:102 Diffuse large B-cell lymphoma (DLBCL) 74:110 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 1 22 theme large 82:86 arg1 DLBCL 105:109 DLBCL 105:109 DLBCL 105:109 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 4 23 theme proximal 614:621 arg1 signaling 627:635 proximal BCR signaling 614:635 proximal BCR signaling in ABC DLBCL 614:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 0 24 theme N-linked 10:17 arg1 Glycosylation 19:31 N-linked Glycosylation 10:31 N-linked Glycosylation 10:31 Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas. 37141112 1 25 theme B-cell 88:93 arg1 lymphoma 95:102 Diffuse large B-cell lymphoma 74:102 Diffuse large B-cell lymphoma (DLBCL) 74:110 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 1 25 theme B-cell 88:93 arg1 DLBCL 105:109 DLBCL 105:109 DLBCL 105:109 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 3 26 theme Constitutive 383:394 arg1 signaling 400:408 Constitutive BCR signaling 383:408 Constitutive BCR signaling 383:408 Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase. 37141112 6 27 theme PI3 929:931 arg1 kinase 933:938 PI3 kinase 929:938 PI3 kinase 929:938 OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. 37141112 2 28 from engagement 221:230 arg1 tumors 266:271 ABC tumors 262:271 ABC tumors 262:271 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 3 29 theme BCR 396:398 arg1 signaling 400:408 Constitutive BCR signaling 383:408 Constitutive BCR signaling 383:408 Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase. 37141112 7 30 theme aggressive 1154:1163 arg1 cancers 1165:1171 these aggressive cancers 1148:1171 these aggressive cancers 1148:1171 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 7 31 theme DLBCL 1063:1067 arg1 models 1041:1046 models 1041:1046 models of ABC and GCB DLBCL 1041:1067 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 2 32 theme ABC 262:264 arg1 tumors 266:271 ABC tumors 262:271 ABC tumors 262:271 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 4 33 from indicator 601:609 arg1 DLBCL 644:648 ABC DLBCL 640:648 ABC DLBCL 640:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 1 34 theme germinal 167:174 arg1 center 176:181 germinal center 167:181 germinal center B-cell-like (GCB) 167:199 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 7 35 theme cancers 1165:1171 arg1 treatment 1135:1143 the treatment 1131:1143 the treatment of these aggressive cancers 1131:1171 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 6 36 with association 889:899 arg1 CD22 906:909 CD22 906:909 CD22 906:909 OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. 37141112 1 37 theme center 176:181 arg1 GCB 196:198 GCB 196:198 GCB 196:198 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 1 37 theme center 176:181 arg1 B-cell-like 183:193 germinal center B-cell-like 167:193 germinal center B-cell-like (GCB) 167:199 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 3 38 theme PI3 466:468 arg1 kinase 470:475 PI3 kinase 466:475 PI3 kinase 466:475 Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase. 37141112 1 39 theme B-cell-like 183:193 arg1 DLCBL 201:205 activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL 135:205 activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL 135:205 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 4 40 theme signaling 627:635 arg1 indicator 601:609 an indicator 598:609 an indicator of proximal BCR signaling in ABC DLBCL 598:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 4 40 theme signaling 627:635 arg1 target 578:583 a direct transcriptional target 553:583 a direct transcriptional target of NF-kB 553:592 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 4 40 theme signaling 627:635 arg1 IRF4 547:550 IRF4 547:550 IRF4 547:550 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 2 41 theme PI3 371:373 arg1 kinase 375:380 PI3 kinase 371:380 PI3 kinase 371:380 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 4 42 theme BCR 623:625 arg1 signaling 627:635 proximal BCR signaling 614:635 proximal BCR signaling in ABC DLBCL 614:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 4 43 theme genome-wide 489:499 arg1 screens 513:519 genome-wide CRISPR-Cas9 screens 489:519 genome-wide CRISPR-Cas9 screens 489:519 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 5 44 theme N-linked 681:688 arg1 glycosylation 698:710 N-linked protein glycosylation 681:710 N-linked protein glycosylation 681:710 Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. 37141112 3 45 from essential 413:421 arg1 tumors 435:440 some GCB tumors 426:440 some GCB tumors 426:440 Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase. 37141112 4 46 theme indicator 601:609 arg1 regulators 533:542 regulators 533:542 regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL 533:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 0 47 theme Aggressive 52:61 arg1 Lymphomas 63:71 Aggressive Lymphomas 52:71 Aggressive Lymphomas 52:71 Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas. 37141112 6 48 theme NF-kB 944:948 arg1 activation 950:959 PI3 kinase and NF-kB activation 929:959 PI3 kinase and NF-kB activation 929:959 OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. 37141112 3 49 theme GCB 431:433 arg1 tumors 435:440 some GCB tumors 426:440 some GCB tumors 426:440 Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase. 37141112 7 50 theme GCB 1059:1061 arg1 DLBCL 1063:1067 ABC and GCB DLBCL 1051:1067 DLBCL 1063:1067 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 6 51 theme kinase 933:938 arg1 activation 950:959 PI3 kinase and NF-kB activation 929:959 PI3 kinase and NF-kB activation 929:959 OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. 37141112 7 52 theme ABC 1051:1053 arg1 DLBCL 1063:1067 ABC and GCB DLBCL 1051:1067 DLBCL 1063:1067 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 6 53 theme BCR 834:836 arg1 clustering 838:847 BCR clustering 834:847 BCR clustering 834:847 OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. 37141112 1 54 dep ABC 158:160 arg1 like 152:155 like 152:155 like 152:155 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 4 55 theme CRISPR-Cas9 501:511 arg1 screens 513:519 genome-wide CRISPR-Cas9 screens 489:519 genome-wide CRISPR-Cas9 screens 489:519 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 2 56 theme B-cell 235:240 arg1 BCRs 253:256 BCRs 253:256 BCRs 253:256 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 2 56 theme B-cell 235:240 arg1 receptors 242:250 B-cell receptors 235:250 B-cell receptors (BCRs) 235:257 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 4 57 theme ABC 640:642 arg1 DLBCL 644:648 ABC DLBCL 640:648 ABC DLBCL 640:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 4 58 theme target 578:583 arg1 regulators 533:542 regulators 533:542 regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL 533:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 2 59 theme receptors 242:250 arg1 engagement 221:230 Self-antigen engagement 208:230 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors 208:271 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 6 60 theme glycosylation 812:824 arg1 inhibition 794:803 OST-B inhibition 788:803 OST-B inhibition of BCR glycosylation 788:824 OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. 37141112 7 61 theme OST-B 1015:1019 arg1 inactivation 1021:1032 OST-B inactivation 1015:1032 OST-B inactivation 1015:1032 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 7 62 theme proximal 991:998 arg1 signaling 1004:1012 proximal BCR signaling 991:1012 proximal BCR signaling 991:1012 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 1 63 theme activated 135:143 arg1 DLCBL 201:205 activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL 135:205 activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL 135:205 Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. 37141112 4 64 theme transcriptional 562:576 arg1 target 578:583 a direct transcriptional target 553:583 a direct transcriptional target of NF-kB 553:592 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 5 65 theme oligosaccharyltransferase-B 719:745 arg1 complex 755:761 the oligosaccharyltransferase-B (OST-B) complex 715:761 the oligosaccharyltransferase-B (OST-B) complex 715:761 Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. 37141112 6 66 theme BCR 808:810 arg1 glycosylation 812:824 BCR glycosylation 808:824 BCR glycosylation 808:824 OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. 37141112 7 67 theme BCR 1000:1002 arg1 signaling 1004:1012 proximal BCR signaling 991:1012 proximal BCR signaling 991:1012 By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers. 37141112 4 68 theme NF-kB 588:592 arg1 indicator 601:609 an indicator 598:609 an indicator of proximal BCR signaling in ABC DLBCL 598:648 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 4 68 theme NF-kB 588:592 arg1 target 578:583 a direct transcriptional target 553:583 a direct transcriptional target of NF-kB 553:592 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 4 68 theme NF-kB 588:592 arg1 IRF4 547:550 IRF4 547:550 IRF4 547:550 We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. 37141112 0 69 theme Lymphomas 63:71 arg1 Therapy 41:47 the Therapy 37:47 the Therapy of Aggressive Lymphomas 37:71 Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas. 37141112 2 70 theme Self-antigen 208:219 arg1 engagement 221:230 Self-antigen engagement 208:230 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors 208:271 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 37141112 2 71 theme active 326:331 arg1 signaling 333:341 chronic active signaling 318:341 chronic active signaling 318:341 Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. 36790175 6 0 theme common 918:923 arg1 transport 849:857 Electron transport 840:857 Electron transport through mitochondrial respiratory complexes I to IV 840:909 Electron transport through mitochondrial respiratory complexes I to IV is the common process of oxidative phosphorylation. 36790175 6 0 theme common 918:923 arg1 process 925:931 the common process 914:931 the common process of oxidative phosphorylation 914:960 Electron transport through mitochondrial respiratory complexes I to IV is the common process of oxidative phosphorylation. 36790175 4 1 theme genes 550:554 arg1 total 510:514 A total 508:514 A total of 3,454 differentially expressed genes and 260 differential metabolites 508:587 A total of 3,454 differentially expressed genes and 260 differential metabolites were identified in the xy12-treated C. albicans by RNA-seq and non-targeted metabolomics. 36790175 14 2 theme fungi-specific 2506:2519 arg1 proteins 2543:2550 fungi-specific mitochondrial complex proteins 2506:2550 fungi-specific mitochondrial complex proteins 2506:2550 Targeting fungi-specific mitochondrial complex proteins has been reported as a promising antifungal strategy. 36790175 10 3 theme drugs 1949:1953 arg1 development 1901:1911 the development 1897:1911 the development of mitochondria-targeted antifungal drugs 1897:1953 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 7 4 theme complex 1145:1151 arg1 III- 1153:1156 mitochondrial complex III- 1131:1156 mitochondrial complex III- 1131:1156 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 1 5 theme antifungal 247:256 arg1 activities 258:267 enhanced antifungal activities 238:267 enhanced antifungal activities 238:267 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 9 6 theme cell 1668:1671 arg1 mannoproteins 1687:1699 decreased cell wall N-linked mannoproteins 1658:1699 decreased cell wall N-linked mannoproteins 1658:1699 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 6 theme cell 1668:1671 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 6 theme cell 1668:1671 arg1 mutants 1489:1495 the CI-deficient mutants 1472:1495 the CI-deficient mutants 1472:1495 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 15 7 theme mitochondrial 2671:2683 arg1 I 2693:2693 C. albicans mitochondrial complex I 2659:2693 C. albicans mitochondrial complex I 2659:2693 Our study provided a new lead compound for targeting C. albicans mitochondrial complex I, which could be beneficial for discovering novel antifungal drugs. 36790175 9 8 theme N-linked 1678:1685 arg1 mannoproteins 1687:1699 decreased cell wall N-linked mannoproteins 1658:1699 decreased cell wall N-linked mannoproteins 1658:1699 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 8 theme N-linked 1678:1685 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 8 theme N-linked 1678:1685 arg1 mutants 1489:1495 the CI-deficient mutants 1472:1495 the CI-deficient mutants 1472:1495 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 12 9 theme SM21 2179:2182 arg1 modification 2145:2156 the modification 2141:2156 the modification of the pyrylium salt SM21 2141:2182 Based on the modification of the pyrylium salt SM21, a new lead compound, xy12, was synthesized which was effective against Candida species both in vitro and in vivo. 36790175 7 10 theme increased 1104:1112 arg1 sensitivities 1114:1126 increased sensitivities 1104:1126 increased sensitivities in mitochondrial complex III- and IV-deficient mutants 1104:1181 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 7 11 theme antifungal 1202:1211 arg1 effects 1213:1219 the antifungal effects 1198:1219 the antifungal effects of xy12 1198:1227 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 7 11 theme antifungal 1202:1211 arg1 dependent 1234:1242 dependent 1234:1242 dependent 1234:1242 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 15 12 theme C. 2659:2660 arg1 albicans 2662:2669 C. albicans 2659:2669 C. albicans mitochondrial complex I 2659:2693 Our study provided a new lead compound for targeting C. albicans mitochondrial complex I, which could be beneficial for discovering novel antifungal drugs. 36790175 13 13 theme transcriptome 2340:2352 arg1 analysis 2324:2331 conjoined analysis 2314:2331 conjoined analysis of the transcriptome and metabolome 2314:2367 In this study, conjoined analysis of the transcriptome and metabolome elucidated the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans. 36790175 13 14 theme metabolome 2358:2367 arg1 analysis 2324:2331 conjoined analysis 2314:2331 conjoined analysis of the transcriptome and metabolome 2314:2367 In this study, conjoined analysis of the transcriptome and metabolome elucidated the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans. 36790175 11 15 theme antifungal 2114:2123 arg1 drugs 2125:2129 clinical antifungal drugs 2105:2129 clinical antifungal drugs 2105:2129 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 11 16 theme drugs 2001:2005 arg1 development 1971:1981 The development 1967:1981 IMPORTANCE The development of new antifungal drugs 1956:2005 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 5 17 theme KEGG 694:697 arg1 analysis 718:725 KEGG pathway enrichment analysis 694:725 KEGG pathway enrichment analysis 694:725 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 15 18 theme lead 2631:2634 arg1 compound 2636:2643 a new lead compound 2625:2643 a new lead compound for targeting C. albicans mitochondrial complex I, which could be beneficial for discovering novel antifungal drugs 2625:2759 Our study provided a new lead compound for targeting C. albicans mitochondrial complex I, which could be beneficial for discovering novel antifungal drugs. 36790175 5 19 theme xy12 834:837 arg1 action 824:829 action 824:829 action of xy12 824:837 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 4 20 theme C. 625:626 arg1 albicans 628:635 the xy12-treated C. albicans 608:635 the xy12-treated C. albicans 608:635 A total of 3,454 differentially expressed genes and 260 differential metabolites were identified in the xy12-treated C. albicans by RNA-seq and non-targeted metabolomics. 36790175 5 21 theme enrichment 707:716 arg1 analysis 718:725 KEGG pathway enrichment analysis 694:725 KEGG pathway enrichment analysis 694:725 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 1 22 theme new 204:206 arg1 derivative 222:231 a new pyrylium salt derivative 202:231 a new pyrylium salt derivative with enhanced antifungal activities 202:267 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 1 22 theme new 204:206 arg1 xy12 196:199 xy12 196:199 xy12 196:199 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 6 23 theme phosphorylation 946:960 arg1 transport 849:857 Electron transport 840:857 Electron transport through mitochondrial respiratory complexes I to IV 840:909 Electron transport through mitochondrial respiratory complexes I to IV is the common process of oxidative phosphorylation. 36790175 6 23 theme phosphorylation 946:960 arg1 process 925:931 the common process 914:931 the common process of oxidative phosphorylation 914:960 Electron transport through mitochondrial respiratory complexes I to IV is the common process of oxidative phosphorylation. 36790175 7 24 theme complex 1067:1073 arg1 mutants 1092:1098 mitochondrial complex I (CI)-deficient mutants 1053:1098 mitochondrial complex I (CI)-deficient mutants 1053:1098 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 10 25 theme complex 1835:1841 arg1 I 1843:1843 mitochondrial complex I 1821:1843 mitochondrial complex I in C. albicans 1821:1858 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 0 26 from Complex 119:125 arg1 albicans 140:147 Candida albicans 132:147 Candida albicans 132:147 Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans. 36790175 8 27 theme CI 1322:1323 arg1 rotenone 1296:1303 rotenone 1296:1303 rotenone 1296:1303 Consistently, xy12 exhibited antagonism with rotenone, an inhibitor of CI, and significantly inhibited the expression and activity of CI. 36790175 8 27 theme CI 1322:1323 arg1 inhibitor 1309:1317 an inhibitor 1306:1317 an inhibitor of CI 1306:1323 Consistently, xy12 exhibited antagonism with rotenone, an inhibitor of CI, and significantly inhibited the expression and activity of CI. 36790175 9 28 theme xy12-treated 1422:1433 arg1 albicans 1438:1445 the xy12-treated C. albicans 1418:1445 the xy12-treated C. albicans 1418:1445 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 11 29 theme resistance 2057:2066 arg1 problem 2035:2041 the problem 2031:2041 the problem of antifungal resistance 2031:2066 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 7 30 theme wild-type 1000:1008 arg1 SC5314 1010:1015 the wild-type SC5314 996:1015 the wild-type SC5314 996:1015 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 9 31 theme decreased 1506:1514 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 0 32 theme Potent 64:69 arg1 Salt 91:94 the Potent Antifungal Pyrylium Salt 60:94 the Potent Antifungal Pyrylium Salt 60:94 Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans. 36790175 0 33 theme Pyrylium 82:89 arg1 Salt 91:94 the Potent Antifungal Pyrylium Salt 60:94 the Potent Antifungal Pyrylium Salt 60:94 Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans. 36790175 1 34 theme structural 163:172 arg1 modification 174:185 the structural modification 159:185 the structural modification of SM21 159:193 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 14 35 theme promising 2575:2583 arg1 strategy 2596:2603 a promising antifungal strategy 2573:2603 a promising antifungal strategy 2573:2603 Targeting fungi-specific mitochondrial complex proteins has been reported as a promising antifungal strategy. 36790175 9 36 theme membrane 1554:1561 arg1 potential 1563:1571 reduced mitochondrial membrane potential 1532:1571 reduced mitochondrial membrane potential 1532:1571 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 36 theme membrane 1554:1561 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 36 theme membrane 1554:1561 arg1 mutants 1489:1495 the CI-deficient mutants 1472:1495 the CI-deficient mutants 1472:1495 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 10 37 from I 1843:1843 arg1 albicans 1851:1858 C. albicans 1848:1858 C. albicans 1848:1858 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 14 38 theme antifungal 2585:2594 arg1 strategy 2596:2603 a promising antifungal strategy 2573:2603 a promising antifungal strategy 2573:2603 Targeting fungi-specific mitochondrial complex proteins has been reported as a promising antifungal strategy. 36790175 11 39 theme new 1986:1988 arg1 drugs 2001:2005 new antifungal drugs 1986:2005 new antifungal drugs 1986:2005 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 5 40 theme phosphorylation 766:780 arg1 inhibition 742:751 inhibition 742:751 inhibition of oxidative phosphorylation 742:780 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 5 40 theme phosphorylation 766:780 arg1 mechanism 811:819 the important antifungal mechanism 786:819 the important antifungal mechanism of action of xy12 786:837 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 13 41 theme complex 2470:2476 arg1 activity 2444:2451 the activity 2440:2451 the activity of mitochondrial complex I in C. albicans 2440:2493 In this study, conjoined analysis of the transcriptome and metabolome elucidated the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans. 36790175 8 42 theme CI 1385:1386 arg1 activity 1373:1380 activity 1373:1380 activity 1373:1380 Consistently, xy12 exhibited antagonism with rotenone, an inhibitor of CI, and significantly inhibited the expression and activity of CI. 36790175 8 42 theme CI 1385:1386 arg1 expression 1358:1367 expression 1358:1367 expression 1358:1367 Consistently, xy12 exhibited antagonism with rotenone, an inhibitor of CI, and significantly inhibited the expression and activity of CI. 36790175 0 43 theme Combined 0:7 arg1 Transcriptome 9:21 Combined Transcriptome and Metabolome Analysis 0:45 Transcriptome 9:21 Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans. 36790175 5 44 theme action 824:829 arg1 mechanism 811:819 the important antifungal mechanism 786:819 the important antifungal mechanism of action of xy12 786:837 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 5 44 theme action 824:829 arg1 inhibition 742:751 inhibition 742:751 inhibition of oxidative phosphorylation 742:780 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 6 45 theme respiratory 881:891 arg1 complexes 893:901 mitochondrial respiratory complexes I to IV 867:909 mitochondrial respiratory complexes I to IV 867:909 Electron transport through mitochondrial respiratory complexes I to IV is the common process of oxidative phosphorylation. 36790175 9 46 theme DNA 1596:1598 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 46 theme DNA 1596:1598 arg1 loss 1574:1577 loss 1574:1577 loss of mitochondrial DNA 1574:1598 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 46 theme DNA 1596:1598 arg1 potential 1563:1571 reduced mitochondrial membrane potential 1532:1571 reduced mitochondrial membrane potential 1532:1571 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 46 theme DNA 1596:1598 arg1 mannoproteins 1687:1699 decreased cell wall N-linked mannoproteins 1658:1699 decreased cell wall N-linked mannoproteins 1658:1699 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 46 theme DNA 1596:1598 arg1 inability 1601:1609 inability 1601:1609 inability to utilize nonfermentative carbon sources 1601:1651 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 46 theme DNA 1596:1598 arg1 mutants 1489:1495 the CI-deficient mutants 1472:1495 the CI-deficient mutants 1472:1495 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 13 47 theme action 2408:2413 arg1 mechanism 2395:2403 the antifungal mechanism 2380:2403 the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans 2380:2493 In this study, conjoined analysis of the transcriptome and metabolome elucidated the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans. 36790175 10 48 theme novel 1873:1877 arg1 compound 1884:1891 a novel lead compound 1871:1891 a novel lead compound for the development of mitochondria-targeted antifungal drugs 1871:1953 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 2 49 theme Candida 320:326 arg1 albicans 328:335 Candida albicans 320:335 Candida albicans 320:335 The MICs (MIC90) of xy12 against Candida albicans ranged from 0.125 to 0.25 μg/mL, about 2-fold lower than those of SM21. 36790175 5 50 theme important 790:798 arg1 mechanism 811:819 the important antifungal mechanism 786:819 the important antifungal mechanism of action of xy12 786:837 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 5 50 theme important 790:798 arg1 inhibition 742:751 inhibition 742:751 inhibition of oxidative phosphorylation 742:780 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 6 51 theme Electron 840:847 arg1 transport 849:857 Electron transport 840:857 Electron transport through mitochondrial respiratory complexes I to IV 840:909 Electron transport through mitochondrial respiratory complexes I to IV is the common process of oxidative phosphorylation. 36790175 6 51 theme Electron 840:847 arg1 process 925:931 the common process 914:931 the common process of oxidative phosphorylation 914:960 Electron transport through mitochondrial respiratory complexes I to IV is the common process of oxidative phosphorylation. 36790175 11 52 dep IMPORTANCE 1956:1965 arg1 development 1971:1981 The development 1967:1981 IMPORTANCE The development of new antifungal drugs 1956:2005 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 12 53 theme lead 2191:2194 arg1 compound 2196:2203 a new lead compound 2185:2203 a new lead compound 2185:2203 Based on the modification of the pyrylium salt SM21, a new lead compound, xy12, was synthesized which was effective against Candida species both in vitro and in vivo. 36790175 12 53 theme lead 2191:2194 arg1 xy12 2206:2209 xy12 2206:2209 xy12 2206:2209 Based on the modification of the pyrylium salt SM21, a new lead compound, xy12, was synthesized which was effective against Candida species both in vitro and in vivo. 36790175 2 54 theme xy12 307:310 arg1 MIC90 297:301 MIC90 297:301 MIC90 297:301 The MICs (MIC90) of xy12 against Candida albicans ranged from 0.125 to 0.25 μg/mL, about 2-fold lower than those of SM21. 36790175 2 54 theme xy12 307:310 arg1 MICs 291:294 The MICs 287:294 The MICs (MIC90) of xy12 against Candida albicans 287:335 The MICs (MIC90) of xy12 against Candida albicans ranged from 0.125 to 0.25 μg/mL, about 2-fold lower than those of SM21. 36790175 15 55 theme new 2627:2629 arg1 compound 2636:2643 a new lead compound 2625:2643 a new lead compound for targeting C. albicans mitochondrial complex I, which could be beneficial for discovering novel antifungal drugs 2625:2759 Our study provided a new lead compound for targeting C. albicans mitochondrial complex I, which could be beneficial for discovering novel antifungal drugs. 36790175 1 56 theme pyrylium 208:215 arg1 derivative 222:231 a new pyrylium salt derivative 202:231 a new pyrylium salt derivative with enhanced antifungal activities 202:267 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 1 56 theme pyrylium 208:215 arg1 xy12 196:199 xy12 196:199 xy12 196:199 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 11 57 theme antifungal 2046:2055 arg1 resistance 2057:2066 antifungal resistance 2046:2066 antifungal resistance 2046:2066 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 9 58 theme carbon 1638:1643 arg1 sources 1645:1651 nonfermentative carbon sources 1622:1651 nonfermentative carbon sources 1622:1651 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 1 59 with derivative 222:231 arg1 activities 258:267 enhanced antifungal activities 238:267 enhanced antifungal activities 238:267 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 4 60 theme differential 564:575 arg1 metabolites 577:587 260 differential metabolites 560:587 260 differential metabolites 560:587 A total of 3,454 differentially expressed genes and 260 differential metabolites were identified in the xy12-treated C. albicans by RNA-seq and non-targeted metabolomics. 36790175 10 61 theme salt 1755:1758 arg1 xy12 1760:1763 the pyrylium salt xy12 1742:1763 the pyrylium salt xy12 1742:1763 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 14 62 theme mitochondrial 2521:2533 arg1 proteins 2543:2550 fungi-specific mitochondrial complex proteins 2506:2550 fungi-specific mitochondrial complex proteins 2506:2550 Targeting fungi-specific mitochondrial complex proteins has been reported as a promising antifungal strategy. 36790175 7 63 theme mitochondrial 1131:1143 arg1 III- 1153:1156 mitochondrial complex III- 1131:1156 mitochondrial complex III- 1131:1156 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 3 64 theme C. 468:469 arg1 albicans 471:478 C. albicans 468:478 C. albicans 468:478 In addition, xy12 inhibited hypha and biofilm formation in C. albicans in a dose-dependent manner. 36790175 1 65 theme enhanced 238:245 arg1 activities 258:267 enhanced antifungal activities 238:267 enhanced antifungal activities 238:267 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 9 66 theme decreased 1658:1666 arg1 mannoproteins 1687:1699 decreased cell wall N-linked mannoproteins 1658:1699 decreased cell wall N-linked mannoproteins 1658:1699 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 66 theme decreased 1658:1666 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 66 theme decreased 1658:1666 arg1 mutants 1489:1495 the CI-deficient mutants 1472:1495 the CI-deficient mutants 1472:1495 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 4 67 theme expressed 540:548 arg1 genes 550:554 3,454 differentially expressed genes 519:554 3,454 differentially expressed genes 519:554 A total of 3,454 differentially expressed genes and 260 differential metabolites were identified in the xy12-treated C. albicans by RNA-seq and non-targeted metabolomics. 36790175 10 68 theme antifungal 1938:1947 arg1 drugs 1949:1953 mitochondria-targeted antifungal drugs 1916:1953 mitochondria-targeted antifungal drugs 1916:1953 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 10 69 theme oxidative 1781:1789 arg1 phosphorylation 1791:1805 oxidative phosphorylation 1781:1805 oxidative phosphorylation 1781:1805 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 9 70 theme C. 1435:1436 arg1 albicans 1438:1445 the xy12-treated C. albicans 1418:1445 the xy12-treated C. albicans 1418:1445 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 11 71 theme limited 2086:2092 arg1 drugs 2125:2129 clinical antifungal drugs 2105:2129 clinical antifungal drugs 2105:2129 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 11 71 theme limited 2086:2092 arg1 variety 2094:2100 the limited variety 2082:2100 the limited variety of clinical antifungal drugs 2082:2129 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 9 72 theme wall 1673:1676 arg1 mannoproteins 1687:1699 decreased cell wall N-linked mannoproteins 1658:1699 decreased cell wall N-linked mannoproteins 1658:1699 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 72 theme wall 1673:1676 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 72 theme wall 1673:1676 arg1 mutants 1489:1495 the CI-deficient mutants 1472:1495 the CI-deficient mutants 1472:1495 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 3 73 theme dose-dependent 485:498 arg1 manner 500:505 a dose-dependent manner 483:505 a dose-dependent manner 483:505 In addition, xy12 inhibited hypha and biofilm formation in C. albicans in a dose-dependent manner. 36790175 15 74 theme complex 2685:2691 arg1 I 2693:2693 C. albicans mitochondrial complex I 2659:2693 C. albicans mitochondrial complex I 2659:2693 Our study provided a new lead compound for targeting C. albicans mitochondrial complex I, which could be beneficial for discovering novel antifungal drugs. 36790175 15 75 theme antifungal 2744:2753 arg1 drugs 2755:2759 novel antifungal drugs 2738:2759 novel antifungal drugs 2738:2759 Our study provided a new lead compound for targeting C. albicans mitochondrial complex I, which could be beneficial for discovering novel antifungal drugs. 36790175 12 76 theme salt 2174:2177 arg1 SM21 2179:2182 the pyrylium salt SM21 2161:2182 the pyrylium salt SM21 2161:2182 Based on the modification of the pyrylium salt SM21, a new lead compound, xy12, was synthesized which was effective against Candida species both in vitro and in vivo. 36790175 5 77 theme oxidative 756:764 arg1 phosphorylation 766:780 oxidative phosphorylation 756:780 oxidative phosphorylation 756:780 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 7 78 theme -deficient 1081:1090 arg1 mutants 1092:1098 mitochondrial complex I (CI)-deficient mutants 1053:1098 mitochondrial complex I (CI)-deficient mutants 1053:1098 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 10 79 theme mitochondrial 1821:1833 arg1 I 1843:1843 mitochondrial complex I 1821:1843 mitochondrial complex I in C. albicans 1821:1858 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 15 80 theme albicans 2662:2669 arg1 I 2693:2693 C. albicans mitochondrial complex I 2659:2693 C. albicans mitochondrial complex I 2659:2693 Our study provided a new lead compound for targeting C. albicans mitochondrial complex I, which could be beneficial for discovering novel antifungal drugs. 36790175 1 81 theme SM21 190:193 arg1 modification 174:185 the structural modification 159:185 the structural modification of SM21 159:193 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 4 82 theme RNA-seq 640:646 arg1 metabolomics 665:676 RNA-seq and non-targeted metabolomics 640:676 RNA-seq and non-targeted metabolomics 640:676 A total of 3,454 differentially expressed genes and 260 differential metabolites were identified in the xy12-treated C. albicans by RNA-seq and non-targeted metabolomics. 36790175 0 83 theme Candida 132:138 arg1 albicans 140:147 Candida albicans 132:147 Candida albicans 132:147 Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans. 36790175 13 84 theme xy12 2418:2421 arg1 action 2408:2413 action 2408:2413 action 2408:2413 In this study, conjoined analysis of the transcriptome and metabolome elucidated the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans. 36790175 11 85 theme drugs 2125:2129 arg1 drugs 2125:2129 clinical antifungal drugs 2105:2129 clinical antifungal drugs 2105:2129 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 11 85 theme drugs 2125:2129 arg1 variety 2094:2100 the limited variety 2082:2100 the limited variety of clinical antifungal drugs 2082:2129 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 9 86 theme reduced 1532:1538 arg1 potential 1563:1571 reduced mitochondrial membrane potential 1532:1571 reduced mitochondrial membrane potential 1532:1571 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 86 theme reduced 1532:1538 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 86 theme reduced 1532:1538 arg1 mutants 1489:1495 the CI-deficient mutants 1472:1495 the CI-deficient mutants 1472:1495 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 5 87 theme pathway 699:705 arg1 analysis 718:725 KEGG pathway enrichment analysis 694:725 KEGG pathway enrichment analysis 694:725 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 10 88 theme C. 1848:1849 arg1 albicans 1851:1858 C. albicans 1848:1858 C. albicans 1848:1858 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 9 89 dep inability 1601:1609 arg1 utilize 1614:1620 utilize 1614:1620 to utilize nonfermentative carbon sources 1611:1651 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 90 theme CI-deficient 1476:1487 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 90 theme CI-deficient 1476:1487 arg1 loss 1574:1577 loss 1574:1577 loss of mitochondrial DNA 1574:1598 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 90 theme CI-deficient 1476:1487 arg1 potential 1563:1571 reduced mitochondrial membrane potential 1532:1571 reduced mitochondrial membrane potential 1532:1571 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 90 theme CI-deficient 1476:1487 arg1 mannoproteins 1687:1699 decreased cell wall N-linked mannoproteins 1658:1699 decreased cell wall N-linked mannoproteins 1658:1699 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 90 theme CI-deficient 1476:1487 arg1 inability 1601:1609 inability 1601:1609 inability to utilize nonfermentative carbon sources 1601:1651 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 90 theme CI-deficient 1476:1487 arg1 mutants 1489:1495 the CI-deficient mutants 1472:1495 the CI-deficient mutants 1472:1495 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 11 91 theme clinical 2105:2112 arg1 drugs 2125:2129 clinical antifungal drugs 2105:2129 clinical antifungal drugs 2105:2129 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 4 92 theme xy12-treated 612:623 arg1 albicans 628:635 the xy12-treated C. albicans 608:635 the xy12-treated C. albicans 608:635 A total of 3,454 differentially expressed genes and 260 differential metabolites were identified in the xy12-treated C. albicans by RNA-seq and non-targeted metabolomics. 36790175 7 93 theme xy12 1224:1227 arg1 effects 1213:1219 the antifungal effects 1198:1219 the antifungal effects of xy12 1198:1227 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 7 93 theme xy12 1224:1227 arg1 dependent 1234:1242 dependent 1234:1242 dependent 1234:1242 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 7 94 theme mitochondrial 1053:1065 arg1 mutants 1092:1098 mitochondrial complex I (CI)-deficient mutants 1053:1098 mitochondrial complex I (CI)-deficient mutants 1053:1098 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 11 95 theme antifungal 1990:1999 arg1 drugs 2001:2005 new antifungal drugs 1986:2005 new antifungal drugs 1986:2005 IMPORTANCE The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. 36790175 7 96 theme decreased 1026:1034 arg1 sensitivities 1036:1048 decreased sensitivities 1026:1048 decreased sensitivities in mitochondrial complex I (CI)-deficient mutants 1026:1098 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 6 97 theme oxidative 936:944 arg1 phosphorylation 946:960 oxidative phosphorylation 936:960 oxidative phosphorylation 936:960 Electron transport through mitochondrial respiratory complexes I to IV is the common process of oxidative phosphorylation. 36790175 0 98 theme Antifungal 71:80 arg1 Salt 91:94 the Potent Antifungal Pyrylium Salt 60:94 the Potent Antifungal Pyrylium Salt 60:94 Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans. 36790175 7 99 theme SC5314 1010:1015 arg1 sensitivity 981:991 the sensitivity 977:991 the sensitivity of the wild-type SC5314 to xy12 977:1023 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 9 100 theme ATP 1516:1518 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 4 101 theme non-targeted 652:663 arg1 metabolomics 665:676 RNA-seq and non-targeted metabolomics 640:676 RNA-seq and non-targeted metabolomics 640:676 A total of 3,454 differentially expressed genes and 260 differential metabolites were identified in the xy12-treated C. albicans by RNA-seq and non-targeted metabolomics. 36790175 13 102 from activity 2444:2451 arg1 albicans 2486:2493 C. albicans 2483:2493 C. albicans 2483:2493 In this study, conjoined analysis of the transcriptome and metabolome elucidated the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans. 36790175 0 103 theme Mitochondrial 105:117 arg1 Complex 119:125 Mitochondrial Complex I 105:127 Mitochondrial Complex I in Candida albicans 105:147 Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans. 36790175 12 104 theme pyrylium 2165:2172 arg1 SM21 2179:2182 the pyrylium salt SM21 2161:2182 the pyrylium salt SM21 2161:2182 Based on the modification of the pyrylium salt SM21, a new lead compound, xy12, was synthesized which was effective against Candida species both in vitro and in vivo. 36790175 9 105 theme mitochondrial 1540:1552 arg1 potential 1563:1571 reduced mitochondrial membrane potential 1532:1571 reduced mitochondrial membrane potential 1532:1571 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 105 theme mitochondrial 1540:1552 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 105 theme mitochondrial 1540:1552 arg1 mutants 1489:1495 the CI-deficient mutants 1472:1495 the CI-deficient mutants 1472:1495 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 12 106 theme Candida 2256:2262 arg1 species 2264:2270 Candida species 2256:2270 Candida species 2256:2270 Based on the modification of the pyrylium salt SM21, a new lead compound, xy12, was synthesized which was effective against Candida species both in vitro and in vivo. 36790175 13 107 theme conjoined 2314:2322 arg1 analysis 2324:2331 conjoined analysis 2314:2331 conjoined analysis of the transcriptome and metabolome 2314:2367 In this study, conjoined analysis of the transcriptome and metabolome elucidated the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans. 36790175 13 108 theme mitochondrial 2456:2468 arg1 complex 2470:2476 mitochondrial complex I 2456:2478 mitochondrial complex I 2456:2478 In this study, conjoined analysis of the transcriptome and metabolome elucidated the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans. 36790175 5 109 theme antifungal 800:809 arg1 mechanism 811:819 the important antifungal mechanism 786:819 the important antifungal mechanism of action of xy12 786:837 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 5 109 theme antifungal 800:809 arg1 inhibition 742:751 inhibition 742:751 inhibition of oxidative phosphorylation 742:780 By integrating KEGG pathway enrichment analysis, we found that inhibition of oxidative phosphorylation was the important antifungal mechanism of action of xy12. 36790175 9 110 link N-linked 1678:1685 arg1 mannoproteins 1687:1699 decreased cell wall N-linked mannoproteins 1658:1699 decreased cell wall N-linked mannoproteins 1658:1699 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 110 link N-linked 1678:1685 arg1 production 1520:1529 decreased ATP production 1506:1529 decreased ATP production 1506:1529 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 9 110 link N-linked 1678:1685 arg1 mutants 1489:1495 the CI-deficient mutants 1472:1495 the CI-deficient mutants 1472:1495 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 0 111 theme Metabolome 27:36 arg1 Analysis 38:45 Combined Transcriptome and Metabolome Analysis 0:45 Analysis 38:45 Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans. 36790175 9 112 theme mitochondrial 1582:1594 arg1 DNA 1596:1598 mitochondrial DNA 1582:1598 mitochondrial DNA 1582:1598 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 4 113 theme metabolites 577:587 arg1 total 510:514 A total 508:514 A total of 3,454 differentially expressed genes and 260 differential metabolites 508:587 A total of 3,454 differentially expressed genes and 260 differential metabolites were identified in the xy12-treated C. albicans by RNA-seq and non-targeted metabolomics. 36790175 2 114 theme 0.125 to 349:356 arg1 0.25 μg/mL 358:367 0.125 to 0.25 μg/mL 349:367 0.125 to 0.25 μg/mL 349:367 The MICs (MIC90) of xy12 against Candida albicans ranged from 0.125 to 0.25 μg/mL, about 2-fold lower than those of SM21. 36790175 7 115 theme IV-deficient 1162:1173 arg1 mutants 1175:1181 IV-deficient mutants 1162:1181 IV-deficient mutants 1162:1181 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 6 116 theme mitochondrial 867:879 arg1 complexes 893:901 mitochondrial respiratory complexes I to IV 867:909 mitochondrial respiratory complexes I to IV 867:909 Electron transport through mitochondrial respiratory complexes I to IV is the common process of oxidative phosphorylation. 36790175 7 117 from sensitivities 1114:1126 arg1 III- 1153:1156 mitochondrial complex III- 1131:1156 mitochondrial complex III- 1131:1156 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 7 117 from sensitivities 1114:1126 arg1 mutants 1175:1181 IV-deficient mutants 1162:1181 IV-deficient mutants 1162:1181 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 7 117 from sensitivities 1114:1126 arg1 mutants 1092:1098 mitochondrial complex I (CI)-deficient mutants 1053:1098 mitochondrial complex I (CI)-deficient mutants 1053:1098 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 10 118 theme lead 1879:1882 arg1 compound 1884:1891 a novel lead compound 1871:1891 a novel lead compound for the development of mitochondria-targeted antifungal drugs 1871:1953 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 15 119 theme novel 2738:2742 arg1 drugs 2755:2759 novel antifungal drugs 2738:2759 novel antifungal drugs 2738:2759 Our study provided a new lead compound for targeting C. albicans mitochondrial complex I, which could be beneficial for discovering novel antifungal drugs. 36790175 9 120 from phenotypes 1404:1413 arg1 albicans 1438:1445 the xy12-treated C. albicans 1418:1445 the xy12-treated C. albicans 1418:1445 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 10 121 theme mitochondria-targeted 1916:1936 arg1 drugs 1949:1953 mitochondria-targeted antifungal drugs 1916:1953 mitochondria-targeted antifungal drugs 1916:1953 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36790175 13 122 dep transcriptome 2340:2352 arg1 the 2336:2338 the 2336:2338 the 2336:2338 In this study, conjoined analysis of the transcriptome and metabolome elucidated the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans. 36790175 9 123 theme nonfermentative 1622:1636 arg1 sources 1645:1651 nonfermentative carbon sources 1622:1651 nonfermentative carbon sources 1622:1651 Meanwhile, the phenotypes in the xy12-treated C. albicans were similar to those in the CI-deficient mutants, such as decreased ATP production, reduced mitochondrial membrane potential, loss of mitochondrial DNA, inability to utilize nonfermentative carbon sources, and decreased cell wall N-linked mannoproteins. 36790175 8 124 dep expression 1358:1367 arg1 the 1354:1356 the 1354:1356 the 1354:1356 Consistently, xy12 exhibited antagonism with rotenone, an inhibitor of CI, and significantly inhibited the expression and activity of CI. 36790175 7 125 from sensitivities 1036:1048 arg1 III- 1153:1156 mitochondrial complex III- 1131:1156 mitochondrial complex III- 1131:1156 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 7 125 from sensitivities 1036:1048 arg1 mutants 1175:1181 IV-deficient mutants 1162:1181 IV-deficient mutants 1162:1181 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 7 125 from sensitivities 1036:1048 arg1 mutants 1092:1098 mitochondrial complex I (CI)-deficient mutants 1053:1098 mitochondrial complex I (CI)-deficient mutants 1053:1098 Compared with the sensitivity of the wild-type SC5314 to xy12, decreased sensitivities in mitochondrial complex I (CI)-deficient mutants and increased sensitivities in mitochondrial complex III- and IV-deficient mutants suggested that the antifungal effects of xy12 were dependent on CI. 36790175 12 126 theme new 2187:2189 arg1 compound 2196:2203 a new lead compound 2185:2203 a new lead compound 2185:2203 Based on the modification of the pyrylium salt SM21, a new lead compound, xy12, was synthesized which was effective against Candida species both in vitro and in vivo. 36790175 12 126 theme new 2187:2189 arg1 xy12 2206:2209 xy12 2206:2209 xy12 2206:2209 Based on the modification of the pyrylium salt SM21, a new lead compound, xy12, was synthesized which was effective against Candida species both in vitro and in vivo. 36790175 3 127 theme biofilm 447:453 arg1 formation 455:463 biofilm formation 447:463 biofilm formation 447:463 In addition, xy12 inhibited hypha and biofilm formation in C. albicans in a dose-dependent manner. 36790175 1 128 theme salt 217:220 arg1 derivative 222:231 a new pyrylium salt derivative 202:231 a new pyrylium salt derivative with enhanced antifungal activities 202:267 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 1 128 theme salt 217:220 arg1 xy12 196:199 xy12 196:199 xy12 196:199 Based on the structural modification of SM21, xy12, a new pyrylium salt derivative with enhanced antifungal activities, was synthesized. 36790175 14 129 theme complex 2535:2541 arg1 proteins 2543:2550 fungi-specific mitochondrial complex proteins 2506:2550 fungi-specific mitochondrial complex proteins 2506:2550 Targeting fungi-specific mitochondrial complex proteins has been reported as a promising antifungal strategy. 36790175 13 130 theme antifungal 2384:2393 arg1 mechanism 2395:2403 the antifungal mechanism 2380:2403 the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans 2380:2493 In this study, conjoined analysis of the transcriptome and metabolome elucidated the antifungal mechanism of action of xy12, which inhibited the activity of mitochondrial complex I in C. albicans. 36790175 6 131 dep IV 908:909 arg1 to 905:906 to 905:906 to 905:906 Electron transport through mitochondrial respiratory complexes I to IV is the common process of oxidative phosphorylation. 36790175 10 132 theme pyrylium 1746:1753 arg1 xy12 1760:1763 the pyrylium salt xy12 1742:1763 the pyrylium salt xy12 1742:1763 Collectively, our results revealed that the pyrylium salt xy12 could constrain oxidative phosphorylation by inhibiting mitochondrial complex I in C. albicans, providing a novel lead compound for the development of mitochondria-targeted antifungal drugs. 36768830 5 0 theme carbohydrate 771:782 arg1 antigens 784:791 carbohydrate antigens 771:791 carbohydrate antigens expressed in breast cancer 771:818 In this study, the reactivity of anti-CSPG4 mAbs was characterized with a peptide mimetic of carbohydrate antigens expressed in breast cancer. 36768830 7 1 theme breast 1085:1090 arg1 cells 1099:1103 triple-negative breast cancer cells 1069:1103 triple-negative breast cancer cells 1069:1103 The mAb VT68.2 displayed a distinctly strong binding to a CMP (P10s) and bound to triple-negative breast cancer cells. 36768830 10 2 theme glycoform 1336:1344 arg1 reactivity 1346:1355 the glycoform reactivity 1332:1355 the glycoform reactivity of an anti-CSPG4 antibody 1332:1381 These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides. 36768830 1 3 theme monoclonal 150:159 arg1 mAbs 173:176 mAbs 173:176 mAbs 173:176 The anti-CSPG4 monoclonal antibodies (mAbs) have shown anti-tumor activity and therapeutic potential for treating breast cancer. 36768830 1 3 theme monoclonal 150:159 arg1 antibodies 161:170 The anti-CSPG4 monoclonal antibodies 135:170 The anti-CSPG4 monoclonal antibodies (mAbs) 135:177 The anti-CSPG4 monoclonal antibodies (mAbs) have shown anti-tumor activity and therapeutic potential for treating breast cancer. 36768830 1 4 theme breast 249:254 arg1 cancer 256:261 breast cancer 249:261 breast cancer 249:261 The anti-CSPG4 monoclonal antibodies (mAbs) have shown anti-tumor activity and therapeutic potential for treating breast cancer. 36768830 5 5 theme anti-CSPG4 711:720 arg1 mAbs 722:725 anti-CSPG4 mAbs 711:725 anti-CSPG4 mAbs 711:725 In this study, the reactivity of anti-CSPG4 mAbs was characterized with a peptide mimetic of carbohydrate antigens expressed in breast cancer. 36768830 7 6 theme cancer 1092:1097 arg1 cells 1099:1103 triple-negative breast cancer cells 1069:1103 triple-negative breast cancer cells 1069:1103 The mAb VT68.2 displayed a distinctly strong binding to a CMP (P10s) and bound to triple-negative breast cancer cells. 36768830 6 7 theme flow 828:831 arg1 cytometry 833:841 flow cytometry 828:841 flow cytometry 828:841 ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. 36768830 2 8 from antigen 314:320 arg1 addition 267:274 addition 267:274 addition 267:274 In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. 36768830 4 9 theme tumor 596:600 arg1 cells 602:606 tumor cells 596:606 tumor cells 596:606 Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. 36768830 9 10 theme functional 1235:1244 arg1 assays 1246:1251 The functional assays 1231:1251 The functional assays 1231:1251 The functional assays demonstrated that VT68.2 inhibited cancer cell migration. 36768830 9 11 theme cancer 1288:1293 arg1 migration 1300:1308 cancer cell migration 1288:1308 cancer cell migration 1288:1308 The functional assays demonstrated that VT68.2 inhibited cancer cell migration. 36768830 7 12 theme triple-negative 1069:1083 arg1 cells 1099:1103 triple-negative breast cancer cells 1069:1103 triple-negative breast cancer cells 1069:1103 The mAb VT68.2 displayed a distinctly strong binding to a CMP (P10s) and bound to triple-negative breast cancer cells. 36768830 10 13 theme antibody 1374:1381 arg1 reactivity 1346:1355 the glycoform reactivity 1332:1355 the glycoform reactivity of an anti-CSPG4 antibody 1332:1381 These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides. 36768830 2 14 theme normal-tissue 347:359 arg1 development 361:371 normal-tissue development 347:371 normal-tissue development in humans 347:381 In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. 36768830 5 15 theme antigens 784:791 arg1 mimetic 760:766 mimetic 760:766 mimetic 760:766 In this study, the reactivity of anti-CSPG4 mAbs was characterized with a peptide mimetic of carbohydrate antigens expressed in breast cancer. 36768830 9 16 theme cell 1295:1298 arg1 migration 1300:1308 cancer cell migration 1288:1308 cancer cell migration 1288:1308 The functional assays demonstrated that VT68.2 inhibited cancer cell migration. 36768830 10 17 theme tumor-specific 1464:1477 arg1 glyco-peptides 1479:1492 tumor-specific glyco-peptides 1464:1492 tumor-specific glyco-peptides 1464:1492 These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides. 36768830 10 18 theme anti-CSPG4 1363:1372 arg1 antibody 1374:1381 an anti-CSPG4 antibody 1360:1381 an anti-CSPG4 antibody 1360:1381 These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides. 36768830 10 19 theme toxic 1423:1427 arg1 approaches 1441:1450 less toxic therapeutic approaches 1418:1450 less toxic therapeutic approaches that target tumor-specific glyco-peptides 1418:1492 These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides. 36768830 3 20 theme serious 442:448 arg1 concern 450:456 a serious concern 440:456 a serious concern 440:456 Therefore, the potential for off-tumor activity remains a serious concern when targeting CSPG4 therapeutically. 36768830 4 21 theme Previous 496:503 arg1 work 505:508 Previous work 496:508 Previous work 496:508 Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. 36768830 8 22 theme higher 1135:1140 arg1 affinity 1142:1149 a higher affinity 1133:1149 a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines 1133:1228 In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. 36768830 4 23 theme anti-CSPG4 571:580 arg1 antibodies 582:591 specific anti-CSPG4 antibodies 562:591 specific anti-CSPG4 antibodies 562:591 Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. 36768830 10 24 theme approaches 1441:1450 arg1 development 1403:1413 the development 1399:1413 the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides 1399:1492 These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides. 36768830 2 25 theme tumor-associated 297:312 arg1 CSPG4 277:281 CSPG4 277:281 CSPG4 277:281 In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. 36768830 2 25 theme tumor-associated 297:312 arg1 antigen 314:320 a dominant tumor-associated antigen 286:320 a dominant tumor-associated antigen that is also involved in normal-tissue development in humans 286:381 In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. 36768830 8 26 theme fucosylated 1205:1215 arg1 lactosamines 1217:1228 fucosylated lactosamines 1205:1228 fucosylated lactosamines 1205:1228 In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. 36768830 8 27 theme N-linked 1155:1162 arg1 glycans 1164:1170 N-linked glycans 1155:1170 N-linked glycans that contain terminal fucose and fucosylated lactosamines 1155:1228 In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. 36768830 4 28 theme specific 562:569 arg1 antibodies 582:591 specific anti-CSPG4 antibodies 562:591 specific anti-CSPG4 antibodies 562:591 Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. 36768830 0 29 theme Carbohydrate 113:124 arg1 Antigen 126:132 a Tumor-Associated Carbohydrate Antigen 94:132 a Tumor-Associated Carbohydrate Antigen 94:132 VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen. 36768830 2 30 from development 361:371 arg1 humans 376:381 humans 376:381 humans 376:381 In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. 36768830 2 31 theme dominant 288:295 arg1 CSPG4 277:281 CSPG4 277:281 CSPG4 277:281 In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. 36768830 2 31 theme dominant 288:295 arg1 antigen 314:320 a dominant tumor-associated antigen 286:320 a dominant tumor-associated antigen that is also involved in normal-tissue development in humans 286:381 In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. 36768830 8 32 link N-linked 1155:1162 arg1 glycans 1164:1170 N-linked glycans 1155:1170 N-linked glycans that contain terminal fucose and fucosylated lactosamines 1155:1228 In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. 36768830 0 33 theme Tumor-Associated 96:111 arg1 Antigen 126:132 a Tumor-Associated Carbohydrate Antigen 94:132 a Tumor-Associated Carbohydrate Antigen 94:132 VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen. 36768830 1 34 theme anti-tumor 190:199 arg1 activity 201:208 anti-tumor activity 190:208 anti-tumor activity 190:208 The anti-CSPG4 monoclonal antibodies (mAbs) have shown anti-tumor activity and therapeutic potential for treating breast cancer. 36768830 0 35 theme Chondroitin 23:33 arg1 CSPG4 59:63 CSPG4 59:63 CSPG4 59:63 VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen. 36768830 0 35 theme Chondroitin 23:33 arg1 Proteoglycan 43:54 Chondroitin Sulfate Proteoglycan 4 23:56 Chondroitin Sulfate Proteoglycan 4 (CSPG4) 23:64 VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen. 36768830 4 36 theme antibodies 582:591 arg1 binding 551:557 the binding 547:557 the binding of specific anti-CSPG4 antibodies to tumor cells 547:606 Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. 36768830 5 37 theme mAbs 722:725 arg1 reactivity 697:706 the reactivity 693:706 the reactivity of anti-CSPG4 mAbs 693:725 In this study, the reactivity of anti-CSPG4 mAbs was characterized with a peptide mimetic of carbohydrate antigens expressed in breast cancer. 36768830 8 38 contain contain 1177:1183 arg2 fucose 1194:1199 terminal fucose 1185:1199 terminal fucose 1185:1199 In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. 36768830 8 38 contain contain 1177:1183 arg2 lactosamines 1217:1228 fucosylated lactosamines 1205:1228 fucosylated lactosamines 1205:1228 In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. 36768830 8 38 contain contain 1177:1183 arg1 glycans 1164:1170 N-linked glycans 1155:1170 N-linked glycans that contain terminal fucose and fucosylated lactosamines 1155:1228 In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. 36768830 3 39 theme off-tumor 413:421 arg1 activity 423:430 off-tumor activity 413:430 off-tumor activity 413:430 Therefore, the potential for off-tumor activity remains a serious concern when targeting CSPG4 therapeutically. 36768830 8 40 gly fucosylated 1205:1215 arg1 lactosamines 1217:1228 fucosylated lactosamines 1205:1228 fucosylated lactosamines 1205:1228 In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. 36768830 4 41 theme contribution 652:663 arg1 specificity 617:627 specificity 617:627 specificity 617:627 Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. 36768830 4 41 theme contribution 652:663 arg1 importance 633:642 importance 633:642 importance 633:642 Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. 36768830 5 42 theme breast 806:811 arg1 cancer 813:818 breast cancer 806:818 breast cancer 806:818 In this study, the reactivity of anti-CSPG4 mAbs was characterized with a peptide mimetic of carbohydrate antigens expressed in breast cancer. 36768830 7 43 theme strong 1025:1030 arg1 binding 1032:1038 a distinctly strong binding 1012:1038 a distinctly strong binding 1012:1038 The mAb VT68.2 displayed a distinctly strong binding to a CMP (P10s) and bound to triple-negative breast cancer cells. 36768830 6 44 theme cancer 960:965 arg1 cells 967:971 cancer cells 960:971 cancer cells 960:971 ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. 36768830 0 45 theme Sulfate 35:41 arg1 CSPG4 59:63 CSPG4 59:63 CSPG4 59:63 VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen. 36768830 0 45 theme Sulfate 35:41 arg1 Proteoglycan 43:54 Chondroitin Sulfate Proteoglycan 4 23:56 Chondroitin Sulfate Proteoglycan 4 (CSPG4) 23:64 VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen. 36768830 6 46 theme microarray 848:857 arg1 assays 859:864 microarray assays 848:864 microarray assays 848:864 ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. 36768830 6 47 theme carbohydrate-mimicking 920:941 arg1 CMPs 953:956 CMPs 953:956 CMPs 953:956 ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. 36768830 6 47 theme carbohydrate-mimicking 920:941 arg1 peptides 943:950 carbohydrate-mimicking peptides 920:950 carbohydrate-mimicking peptides (CMPs) 920:957 ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. 36768830 7 48 theme mAb 991:993 arg1 VT68.2 995:1000 The mAb VT68.2 987:1000 The mAb VT68.2 987:1000 The mAb VT68.2 displayed a distinctly strong binding to a CMP (P10s) and bound to triple-negative breast cancer cells. 36768830 1 49 theme therapeutic 214:224 arg1 potential 226:234 therapeutic potential 214:234 therapeutic potential 214:234 The anti-CSPG4 monoclonal antibodies (mAbs) have shown anti-tumor activity and therapeutic potential for treating breast cancer. 36768830 4 50 dep specificity 617:627 arg1 the 613:615 the 613:615 the 613:615 Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. 36768830 8 51 theme terminal 1185:1192 arg1 fucose 1194:1199 terminal fucose 1185:1199 terminal fucose 1185:1199 In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. 36768830 5 52 theme mimetic 760:766 arg1 peptide 752:758 a peptide 750:758 a peptide mimetic of carbohydrate antigens expressed in breast cancer 750:818 In this study, the reactivity of anti-CSPG4 mAbs was characterized with a peptide mimetic of carbohydrate antigens expressed in breast cancer. 36768830 6 53 used used 871:874 arg2 cytometry 833:841 flow cytometry 828:841 flow cytometry 828:841 ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. 36768830 6 53 used used 871:874 arg2 ELISA 821:825 ELISA 821:825 ELISA 821:825 ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. 36768830 6 53 used used 871:874 arg2 assays 859:864 microarray assays 848:864 microarray assays 848:864 ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. 36768830 0 54 dep VT68.2 0:5 arg1 Antibody 11:18 An Antibody 8:18 VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) 0:64 VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen. 36768830 10 55 theme therapeutic 1429:1439 arg1 approaches 1441:1450 less toxic therapeutic approaches 1418:1450 less toxic therapeutic approaches that target tumor-specific glyco-peptides 1418:1492 These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides. 36135100 8 0 dep in 1203:1204 arg1 vivo 1206:1209 vivo 1206:1209 vivo 1206:1209 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 9 1 theme engineering 1334:1344 arg1 strategy 1346:1353 a new combined engineering strategy 1319:1353 a new combined engineering strategy 1319:1353 CONCLUSIONS Our work proposed a new combined engineering strategy and engineered two liver-tropic AAVs. 36135100 6 2 theme other 1043:1047 arg1 lines 1067:1071 other human tissue cell lines 1043:1071 human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines 969:1071 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 6 3 theme cell 1062:1065 arg1 lines 1067:1071 other human tissue cell lines 1043:1071 human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines 969:1071 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 9 4 theme new 1321:1323 arg1 strategy 1346:1353 a new combined engineering strategy 1319:1353 a new combined engineering strategy 1319:1353 CONCLUSIONS Our work proposed a new combined engineering strategy and engineered two liver-tropic AAVs. 36135100 1 5 theme rAAV 185:188 arg1 vectors 191:197 recombinant adeno-associated viral (rAAV) vectors 149:197 recombinant adeno-associated viral (rAAV) vectors 149:197 OBJECTIVES Gene therapy based on recombinant adeno-associated viral (rAAV) vectors has been proved to be clinically effective for genetic diseases. 36135100 8 6 theme parental 1267:1274 arg1 capsids 1280:1286 their parental AAV capsids 1261:1286 their parental AAV capsids 1261:1286 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 10 7 theme neutralizing 1494:1505 arg1 antibodies 1507:1516 neutralizing antibodies 1494:1516 neutralizing antibodies 1494:1516 We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. 36135100 6 8 theme transduction 942:953 arg1 efficiency 955:964 higher transduction efficiency 935:964 higher transduction efficiency 935:964 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 7 9 theme neutralizing 1145:1156 arg1 antibody 1158:1165 neutralizing antibody 1145:1165 neutralizing antibody 1145:1165 Importantly, all the variants screened out showed lower sensitivity to neutralizing antibody in vitro and in vivo. 36135100 3 10 theme engineering 547:557 arg1 strategy 559:566 an engineering strategy 544:566 an engineering strategy that can obtain mutants with enhanced transduction efficiency coupled with reduced immunogenicity 544:664 Herein, we explored whether there was an engineering strategy that can obtain mutants with enhanced transduction efficiency coupled with reduced immunogenicity. 36135100 4 11 theme new 690:692 arg1 strategy 694:701 a new strategy 688:701 a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif 688:816 METHODS We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. 36135100 9 12 theme combined 1325:1332 arg1 strategy 1346:1353 a new combined engineering strategy 1319:1353 a new combined engineering strategy 1319:1353 CONCLUSIONS Our work proposed a new combined engineering strategy and engineered two liver-tropic AAVs. 36135100 6 13 theme higher 935:940 arg1 efficiency 955:964 higher transduction efficiency 935:964 higher transduction efficiency 935:964 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 10 14 theme lower 1473:1477 arg1 sensitivity 1479:1489 lower sensitivity 1473:1489 lower sensitivity of neutralizing antibodies 1473:1516 We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. 36135100 8 15 theme in 1203:1204 arg1 profiles 1220:1227 the in vivo antibody profiles 1199:1227 the in vivo antibody profiles of variants 1199:1239 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 8 15 theme in 1203:1204 arg1 different 1246:1254 different 1246:1254 different 1246:1254 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 10 16 theme AAV 1418:1420 arg1 variants 1422:1429 several AAV variants 1410:1429 several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies 1410:1516 We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. 36135100 2 17 theme patients 399:406 arg1 number 382:387 a decreasing number 369:387 a decreasing number of target patients 369:406 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 2 17 theme patients 399:406 arg1 delivery 356:363 high dose delivery 346:363 high dose delivery 346:363 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 11 18 theme gene 1616:1619 arg1 therapy 1621:1627 AAV gene therapy 1612:1627 AAV gene therapy 1612:1627 By expanding the gene delivery toolbox, these variants may further facilitate the success of AAV gene therapy. 36135100 0 19 theme Rational 0:7 arg1 engineering 9:19 Rational engineering 0:19 Rational engineering of adeno-associated virus capsid 0:52 Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity. 36135100 2 20 theme target 392:397 arg1 patients 399:406 target patients 392:406 target patients 392:406 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 2 21 theme neutralizing 454:465 arg1 antibodies 467:476 pre-existing neutralizing antibodies 441:476 pre-existing neutralizing antibodies 441:476 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 11 22 theme therapy 1621:1627 arg1 success 1601:1607 the success 1597:1607 the success of AAV gene therapy 1597:1627 By expanding the gene delivery toolbox, these variants may further facilitate the success of AAV gene therapy. 36135100 2 23 theme pre-existing 441:452 arg1 antibodies 467:476 pre-existing neutralizing antibodies 441:476 pre-existing neutralizing antibodies 441:476 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 7 24 theme lower 1124:1128 arg1 sensitivity 1130:1140 lower sensitivity 1124:1140 lower sensitivity to neutralizing antibody 1124:1165 Importantly, all the variants screened out showed lower sensitivity to neutralizing antibody in vitro and in vivo. 36135100 10 25 theme transduction 1445:1456 arg1 efficiency 1458:1467 a higher transduction efficiency 1436:1467 a higher transduction efficiency 1436:1467 We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. 36135100 2 26 theme possible 317:324 arg1 safety 326:331 possible safety concerns 317:340 possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies 317:476 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 4 27 theme PLA2-like 802:810 arg1 motif 812:816 PLA2-like motif 802:816 PLA2-like motif 802:816 METHODS We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. 36135100 8 28 theme AAV 1276:1278 arg1 capsids 1280:1286 their parental AAV capsids 1261:1286 their parental AAV capsids 1261:1286 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 0 29 theme adeno-associated 24:39 arg1 capsid 47:52 adeno-associated virus capsid 24:52 adeno-associated virus capsid 24:52 Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity. 36135100 4 30 theme glycosylation 768:780 arg1 alterations 744:754 alterations 744:754 alterations of N-linked glycosylation 744:780 METHODS We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. 36135100 4 30 theme glycosylation 768:780 arg1 mutation 790:797 the mutation 786:797 the mutation of PLA2-like motif 786:816 METHODS We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. 36135100 10 31 theme higher 1438:1443 arg1 efficiency 1458:1467 a higher transduction efficiency 1436:1467 a higher transduction efficiency 1436:1467 We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. 36135100 1 32 theme OBJECTIVES 116:125 arg1 therapy 132:138 OBJECTIVES Gene therapy 116:138 OBJECTIVES Gene therapy based on recombinant adeno-associated viral (rAAV) vectors 116:197 OBJECTIVES Gene therapy based on recombinant adeno-associated viral (rAAV) vectors has been proved to be clinically effective for genetic diseases. 36135100 10 33 theme antibodies 1507:1516 arg1 efficiency 1458:1467 a higher transduction efficiency 1436:1467 a higher transduction efficiency 1436:1467 We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. 36135100 10 33 theme antibodies 1507:1516 arg1 sensitivity 1479:1489 lower sensitivity 1473:1489 lower sensitivity of neutralizing antibodies 1473:1516 We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. 36135100 2 34 theme high 422:425 arg1 prevalence 427:436 the high prevalence 418:436 the high prevalence of pre-existing neutralizing antibodies 418:476 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 3 35 with mutants 584:590 arg1 efficiency 619:628 enhanced transduction efficiency 597:628 enhanced transduction efficiency coupled with reduced immunogenicity 597:664 Herein, we explored whether there was an engineering strategy that can obtain mutants with enhanced transduction efficiency coupled with reduced immunogenicity. 36135100 6 36 theme human 1006:1010 arg1 hepatocytes 1020:1030 human primary hepatocytes 1006:1030 human primary hepatocytes 1006:1030 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 1 37 theme Gene 127:130 arg1 therapy 132:138 OBJECTIVES Gene therapy 116:138 OBJECTIVES Gene therapy based on recombinant adeno-associated viral (rAAV) vectors 116:197 OBJECTIVES Gene therapy based on recombinant adeno-associated viral (rAAV) vectors has been proved to be clinically effective for genetic diseases. 36135100 2 38 theme decreasing 371:380 arg1 number 382:387 a decreasing number 369:387 a decreasing number of target patients 369:406 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 0 39 theme capsid 47:52 arg1 engineering 9:19 Rational engineering 0:19 Rational engineering of adeno-associated virus capsid 0:52 Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity. 36135100 3 40 theme transduction 606:617 arg1 efficiency 619:628 enhanced transduction efficiency 597:628 enhanced transduction efficiency coupled with reduced immunogenicity 597:664 Herein, we explored whether there was an engineering strategy that can obtain mutants with enhanced transduction efficiency coupled with reduced immunogenicity. 36135100 11 41 theme gene 1536:1539 arg1 toolbox 1550:1556 the gene delivery toolbox 1532:1556 the gene delivery toolbox 1532:1556 By expanding the gene delivery toolbox, these variants may further facilitate the success of AAV gene therapy. 36135100 9 42 theme liver-tropic 1374:1385 arg1 AAVs 1387:1390 two liver-tropic AAVs 1370:1390 two liver-tropic AAVs 1370:1390 CONCLUSIONS Our work proposed a new combined engineering strategy and engineered two liver-tropic AAVs. 36135100 0 43 theme virus 41:45 arg1 capsid 47:52 adeno-associated virus capsid 24:52 adeno-associated virus capsid 24:52 Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity. 36135100 8 44 theme variants 1232:1239 arg1 profiles 1220:1227 the in vivo antibody profiles 1199:1227 the in vivo antibody profiles of variants 1199:1239 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 8 44 theme variants 1232:1239 arg1 different 1246:1254 different 1246:1254 different 1246:1254 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 6 45 theme tissue 1055:1060 arg1 lines 1067:1071 other human tissue cell lines 1043:1071 human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines 969:1071 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 8 46 from capsids 1280:1286 arg1 profiles 1220:1227 the in vivo antibody profiles 1199:1227 the in vivo antibody profiles of variants 1199:1239 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 8 46 from capsids 1280:1286 arg1 different 1246:1254 different 1246:1254 different 1246:1254 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 8 47 theme antibody 1211:1218 arg1 profiles 1220:1227 the in vivo antibody profiles 1199:1227 the in vivo antibody profiles of variants 1199:1239 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 8 47 theme antibody 1211:1218 arg1 different 1246:1254 different 1246:1254 different 1246:1254 Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. 36135100 0 48 theme human 63:67 arg1 tropism 80:86 human hepatocyte tropism 63:86 human hepatocyte tropism 63:86 Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity. 36135100 6 49 theme cell 991:994 arg1 lines 996:1000 human liver carcinoma cell lines 969:1000 human liver carcinoma cell lines 969:1000 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 6 50 theme primary 1012:1018 arg1 hepatocytes 1020:1030 human primary hepatocytes 1006:1030 human primary hepatocytes 1006:1030 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 4 51 dep METHODS 667:673 arg1 described 678:686 described 678:686 described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif 678:816 METHODS We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. 36135100 2 52 theme dose 351:354 arg1 delivery 356:363 high dose delivery 346:363 high dose delivery 346:363 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 2 53 theme antibodies 467:476 arg1 prevalence 427:436 the high prevalence 418:436 the high prevalence of pre-existing neutralizing antibodies 418:476 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 6 54 theme carcinoma 981:989 arg1 lines 996:1000 human liver carcinoma cell lines 969:1000 human liver carcinoma cell lines 969:1000 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 5 55 attach derived 876:882 arg2 variants 867:874 novel variants 861:874 novel variants derived from AAV8 and AAVS3 861:902 With this combined strategy, we generated novel variants derived from AAV8 and AAVS3. 36135100 5 55 attach derived 876:882 arg1 AAV8 889:892 AAV8 889:892 AAV8 889:892 With this combined strategy, we generated novel variants derived from AAV8 and AAVS3. 36135100 5 55 attach derived 876:882 arg1 AAVS3 898:902 AAVS3 898:902 AAVS3 898:902 With this combined strategy, we generated novel variants derived from AAV8 and AAVS3. 36135100 3 56 theme enhanced 597:604 arg1 efficiency 619:628 enhanced transduction efficiency 597:628 enhanced transduction efficiency coupled with reduced immunogenicity 597:664 Herein, we explored whether there was an engineering strategy that can obtain mutants with enhanced transduction efficiency coupled with reduced immunogenicity. 36135100 2 57 theme high 346:349 arg1 delivery 356:363 high dose delivery 346:363 high dose delivery 346:363 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 11 58 theme delivery 1541:1548 arg1 toolbox 1550:1556 the gene delivery toolbox 1532:1556 the gene delivery toolbox 1532:1556 By expanding the gene delivery toolbox, these variants may further facilitate the success of AAV gene therapy. 36135100 6 59 theme liver 975:979 arg1 lines 996:1000 human liver carcinoma cell lines 969:1000 human liver carcinoma cell lines 969:1000 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 5 60 theme combined 829:836 arg1 strategy 838:845 this combined strategy 824:845 this combined strategy 824:845 With this combined strategy, we generated novel variants derived from AAV8 and AAVS3. 36135100 3 61 theme reduced 643:649 arg1 immunogenicity 651:664 reduced immunogenicity 643:664 reduced immunogenicity 643:664 Herein, we explored whether there was an engineering strategy that can obtain mutants with enhanced transduction efficiency coupled with reduced immunogenicity. 36135100 4 62 theme AAV 707:709 arg1 capsids 711:717 AAV capsids 707:717 AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif 707:816 METHODS We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. 36135100 2 63 dep safety 326:331 arg1 concerns 333:340 concerns 333:340 concerns 333:340 However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. 36135100 11 64 theme AAV 1612:1614 arg1 therapy 1621:1627 AAV gene therapy 1612:1627 AAV gene therapy 1612:1627 By expanding the gene delivery toolbox, these variants may further facilitate the success of AAV gene therapy. 36135100 4 65 theme motif 812:816 arg1 alterations 744:754 alterations 744:754 alterations of N-linked glycosylation 744:780 METHODS We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. 36135100 4 65 theme motif 812:816 arg1 mutation 790:797 the mutation 786:797 the mutation of PLA2-like motif 786:816 METHODS We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. 36135100 4 66 link N-linked 759:766 arg1 glycosylation 768:780 N-linked glycosylation 759:780 N-linked glycosylation 759:780 METHODS We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. 36135100 10 67 theme several 1410:1416 arg1 variants 1422:1429 several AAV variants 1410:1429 several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies 1410:1516 We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. 36135100 1 68 theme recombinant 149:159 arg1 vectors 191:197 recombinant adeno-associated viral (rAAV) vectors 149:197 recombinant adeno-associated viral (rAAV) vectors 149:197 OBJECTIVES Gene therapy based on recombinant adeno-associated viral (rAAV) vectors has been proved to be clinically effective for genetic diseases. 36135100 4 69 theme N-linked 759:766 arg1 glycosylation 768:780 N-linked glycosylation 759:780 N-linked glycosylation 759:780 METHODS We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. 36135100 10 70 with variants 1422:1429 arg1 efficiency 1458:1467 a higher transduction efficiency 1436:1467 a higher transduction efficiency 1436:1467 We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. 36135100 10 70 with variants 1422:1429 arg1 sensitivity 1479:1489 lower sensitivity 1473:1489 lower sensitivity of neutralizing antibodies 1473:1516 We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. 36135100 1 71 theme adeno-associated 161:176 arg1 vectors 191:197 recombinant adeno-associated viral (rAAV) vectors 149:197 recombinant adeno-associated viral (rAAV) vectors 149:197 OBJECTIVES Gene therapy based on recombinant adeno-associated viral (rAAV) vectors has been proved to be clinically effective for genetic diseases. 36135100 9 72 theme CONCLUSIONS 1289:1299 arg1 work 1305:1308 CONCLUSIONS Our work 1289:1308 CONCLUSIONS Our work 1289:1308 CONCLUSIONS Our work proposed a new combined engineering strategy and engineered two liver-tropic AAVs. 36135100 1 73 theme genetic 246:252 arg1 diseases 254:261 genetic diseases 246:261 genetic diseases 246:261 OBJECTIVES Gene therapy based on recombinant adeno-associated viral (rAAV) vectors has been proved to be clinically effective for genetic diseases. 36135100 0 74 theme hepatocyte 69:78 arg1 tropism 80:86 human hepatocyte tropism 63:86 human hepatocyte tropism 63:86 Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity. 36135100 6 75 theme human 969:973 arg1 lines 996:1000 human liver carcinoma cell lines 969:1000 human liver carcinoma cell lines 969:1000 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 5 76 theme novel 861:865 arg1 variants 867:874 novel variants 861:874 novel variants derived from AAV8 and AAVS3 861:902 With this combined strategy, we generated novel variants derived from AAV8 and AAVS3. 36135100 6 77 dep RESULTS 905:911 arg1 mediated 926:933 mediated 926:933 mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines 926:1071 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36135100 1 78 theme viral 178:182 arg1 vectors 191:197 recombinant adeno-associated viral (rAAV) vectors 149:197 recombinant adeno-associated viral (rAAV) vectors 149:197 OBJECTIVES Gene therapy based on recombinant adeno-associated viral (rAAV) vectors has been proved to be clinically effective for genetic diseases. 36135100 6 79 theme human 1049:1053 arg1 lines 1067:1071 other human tissue cell lines 1043:1071 human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines 969:1071 RESULTS The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. 36003139 7 0 theme ReN 1446:1448 arg1 cells 1450:1454 ReN cells 1446:1454 ReN cells 1446:1454 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 13 1 theme eCB 2445:2447 arg1 proteins 2462:2469 eCB metabolizing proteins 2445:2469 eCB metabolizing proteins 2445:2469 As such, our data is important for further determining the role of eCB metabolizing proteins and eCB receptors against oxidative stress. 36003139 10 2 theme eCB 2046:2048 arg1 proteins 2050:2057 all eCB proteins 2042:2057 all eCB proteins tested 2042:2064 We determined that sublethal oxidative stress upregulates the expression of all eCB proteins tested. 36003139 13 3 theme proteins 2462:2469 arg1 role 2437:2440 the role 2433:2440 the role of eCB metabolizing proteins and eCB receptors against oxidative stress 2433:2512 As such, our data is important for further determining the role of eCB metabolizing proteins and eCB receptors against oxidative stress. 36003139 3 4 theme numerous 505:512 arg1 processes 541:549 numerous cellular and physiological processes 505:549 numerous cellular and physiological processes 505:549 NAEs are involved in numerous cellular and physiological processes and their concentrations are elevated in response to ischemia and physical trauma to play a role in neuroprotection. 36003139 8 5 theme primary 1666:1672 arg1 neurons 1674:1680 primary neurons 1666:1680 primary neurons 1666:1680 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 8 5 theme primary 1666:1672 arg1 systems 1696:1702 cell model systems 1685:1702 cell model systems 1685:1702 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 8 5 theme primary 1666:1672 arg1 lines 1656:1660 transformed cell lines 1639:1660 transformed cell lines 1639:1660 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 4 6 theme conditions 817:826 arg1 conditions 817:826 conditions 817:826 conditions 817:826 The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. 36003139 4 6 theme conditions 817:826 arg1 variety 806:812 a variety 804:812 a variety of conditions 804:826 The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. 36003139 1 7 theme lipids 175:180 arg1 amides 146:151 N-acyl amides 139:151 N-acyl amides (NAAs) 139:158 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 1 7 theme lipids 175:180 arg1 class 166:170 a class 164:170 a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide 164:374 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 7 8 theme progenitor 1407:1416 arg1 cells 1431:1435 Human stem cell-derived or human neural progenitor cell-derived cells 1367:1435 cells 1431:1435 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 6 9 theme neuroprotection 1185:1199 arg1 system 1153:1158 a more contemporary model system 1127:1158 a more contemporary model system of neurodegeneration and neuroprotection 1127:1199 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 1 10 link N-linked 212:219 arg1 group 206:210 an acyl group 198:210 an acyl group N-linked to an amino acid, neurotransmitter, taurine 198:263 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 8 11 theme model 1690:1694 arg1 neurons 1674:1680 primary neurons 1666:1680 primary neurons 1666:1680 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 8 11 theme model 1690:1694 arg1 systems 1696:1702 cell model systems 1685:1702 cell model systems 1685:1702 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 8 11 theme model 1690:1694 arg1 lines 1656:1660 transformed cell lines 1639:1660 transformed cell lines 1639:1660 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 9 12 theme eCB 1890:1892 arg1 signaling 1898:1906 canonical eCB NAE signaling 1880:1906 canonical eCB NAE signaling 1880:1906 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 6 13 theme action 1261:1266 arg1 mechanism 1248:1256 mechanism 1248:1256 mechanism 1248:1256 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 6 13 theme action 1261:1266 arg1 role 1239:1242 their role 1233:1242 their role 1233:1242 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 6 14 theme model 1147:1151 arg1 system 1153:1158 a more contemporary model system 1127:1158 a more contemporary model system of neurodegeneration and neuroprotection 1127:1199 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 4 15 theme eCB 702:704 arg1 NAEs 706:709 eCB NAEs 702:709 eCB NAEs 702:709 The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. 36003139 6 16 from system 1153:1158 arg1 characterization 1090:1105 Further characterization 1082:1105 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection 1082:1199 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 5 17 theme N-acylethanolamine 978:995 arg1 NAAA 1011:1014 NAAA 1011:1014 NAAA 1011:1014 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 5 17 theme N-acylethanolamine 978:995 arg1 amidase 1002:1008 N-acylethanolamine acid amidase 978:1008 N-acylethanolamine acid amidase (NAAA) 978:1015 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 7 18 theme diseases 1549:1556 arg1 study 1491:1495 the study 1487:1495 the study of human neuronal development and neurodegenerative diseases 1487:1556 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 11 19 theme lesser 2169:2174 arg1 extent 2176:2181 a lesser extent 2167:2181 a lesser extent 2167:2181 In addition, we determined that oxidative stress increases the nuclear localization of FAAH, and to a lesser extent, NAAA and NAPE-PLD. 36003139 12 20 theme oxidative 2253:2261 arg1 stress 2263:2268 oxidative stress 2253:2268 oxidative stress 2253:2268 This study is a first step toward determining how oxidative stress affects CB1, CB2, FAAH, NAAA, and NAPE-PLD expression and their potential defense against oxidative stress. 36003139 0 21 theme progenitor-derived 72:89 arg1 neurons 91:97 human neural progenitor-derived neurons 59:97 human neural progenitor-derived neurons exposed to sub-lethal oxidative stress 59:136 N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress. 36003139 6 22 from utilization 1330:1340 arg1 setting 1358:1364 the clinical setting 1345:1364 the clinical setting 1345:1364 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 2 23 theme cell 453:456 arg1 types 458:462 multiple cell types 444:462 multiple cell types 444:462 These lipids are synthesized in a wide variety of organisms and in multiple cell types, including neurons. 36003139 2 23 theme cell 453:456 arg1 neurons 475:481 neurons 475:481 neurons 475:481 These lipids are synthesized in a wide variety of organisms and in multiple cell types, including neurons. 36003139 1 24 dep group 281:285 arg1 N-acylethanolamines 288:306 N-acylethanolamines 288:306 N-acylethanolamines 288:306 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 1 24 dep group 281:285 arg1 NAEs 311:314 NAEs 311:314 NAEs 311:314 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 6 25 theme better 1323:1328 arg1 utilization 1330:1340 better utilization 1323:1340 better utilization in the clinical setting 1323:1364 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 5 26 theme receptor 885:892 arg1 type 894:897 cannabinoid receptor type 1 873:899 cannabinoid receptor type 1 (CB1) 873:905 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 5 26 theme receptor 885:892 arg1 CB1 902:904 CB1 902:904 CB1 902:904 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 7 27 theme neuronal 1506:1513 arg1 development 1515:1525 human neuronal development 1500:1525 human neuronal development 1500:1525 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 10 28 theme oxidative 1995:2003 arg1 stress 2005:2010 sublethal oxidative stress 1985:2010 sublethal oxidative stress 1985:2010 We determined that sublethal oxidative stress upregulates the expression of all eCB proteins tested. 36003139 0 29 theme sub-lethal 110:119 arg1 stress 131:136 sub-lethal oxidative stress 110:136 sub-lethal oxidative stress 110:136 N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress. 36003139 7 30 theme human 1394:1398 arg1 cells 1431:1435 Human stem cell-derived or human neural progenitor cell-derived cells 1367:1435 cells 1431:1435 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 4 31 theme compounds 745:753 arg1 targets 728:734 the protein targets 716:734 the protein targets of these compounds 716:753 The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. 36003139 6 32 theme oxidative 1295:1303 arg1 stress 1305:1310 oxidative stress 1295:1310 oxidative stress leading to better utilization in the clinical setting 1295:1364 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 5 33 theme N-acyl 1022:1027 arg1 D 1068:1068 N-acyl phosphatidylethanolamine phospholipase D 1022:1068 N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) 1022:1079 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 11 34 theme nuclear 2130:2136 arg1 localization 2138:2149 the nuclear localization 2126:2149 the nuclear localization of FAAH 2126:2157 In addition, we determined that oxidative stress increases the nuclear localization of FAAH, and to a lesser extent, NAAA and NAPE-PLD. 36003139 6 35 from targets 1116:1122 arg1 system 1153:1158 a more contemporary model system 1127:1158 a more contemporary model system of neurodegeneration and neuroprotection 1127:1199 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 0 36 theme N-acylethanolamide 0:17 arg1 enzymes 32:38 N-acylethanolamide metabolizing enzymes 0:38 N-acylethanolamide metabolizing enzymes 0:38 N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress. 36003139 11 37 theme oxidative 2099:2107 arg1 stress 2109:2114 oxidative stress 2099:2114 oxidative stress 2099:2114 In addition, we determined that oxidative stress increases the nuclear localization of FAAH, and to a lesser extent, NAAA and NAPE-PLD. 36003139 4 38 theme protein 720:726 arg1 targets 728:734 the protein targets 716:734 the protein targets of these compounds 716:753 The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. 36003139 1 39 theme ethanolamide 268:279 arg1 group 281:285 ethanolamide group 268:285 ethanolamide group (N-acylethanolamines or NAEs) 268:315 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 5 40 theme receptor 920:927 arg1 type 929:932 cannabinoid receptor type 2 908:934 cannabinoid receptor type 2 (CB2) 908:940 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 5 40 theme receptor 920:927 arg1 CB2 937:939 CB2 937:939 CB2 937:939 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 9 41 theme cell 1764:1767 arg1 cells 1746:1750 ReN cells 1742:1750 ReN cells 1742:1750 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 9 41 theme cell 1764:1767 arg1 system 1775:1780 a superior cell model system 1753:1780 a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection 1753:1848 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 5 42 dep D 1068:1068 arg1 NAPE-PLD 1071:1078 NAPE-PLD 1071:1078 NAPE-PLD 1071:1078 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 13 43 theme eCB 2475:2477 arg1 receptors 2479:2487 eCB receptors 2475:2487 eCB receptors 2475:2487 As such, our data is important for further determining the role of eCB metabolizing proteins and eCB receptors against oxidative stress. 36003139 2 44 theme organisms 427:435 arg1 organisms 427:435 organisms 427:435 organisms 427:435 These lipids are synthesized in a wide variety of organisms and in multiple cell types, including neurons. 36003139 2 44 theme organisms 427:435 arg1 variety 416:422 a wide variety 409:422 a wide variety of organisms 409:435 These lipids are synthesized in a wide variety of organisms and in multiple cell types, including neurons. 36003139 6 45 theme clinical 1349:1356 arg1 setting 1358:1364 the clinical setting 1345:1364 the clinical setting 1345:1364 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 5 46 theme phospholipase 1054:1066 arg1 D 1068:1068 N-acyl phosphatidylethanolamine phospholipase D 1022:1068 N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) 1022:1079 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 12 47 theme potential 2334:2342 arg1 defense 2344:2350 their potential defense 2328:2350 their potential defense against oxidative stress 2328:2375 This study is a first step toward determining how oxidative stress affects CB1, CB2, FAAH, NAAA, and NAPE-PLD expression and their potential defense against oxidative stress. 36003139 1 48 theme N-linked 212:219 arg1 group 206:210 an acyl group 198:210 an acyl group N-linked to an amino acid, neurotransmitter, taurine 198:263 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 4 49 theme clinical 778:785 arg1 intervention 787:798 clinical intervention 778:798 clinical intervention 778:798 The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. 36003139 13 50 theme receptors 2479:2487 arg1 role 2437:2440 the role 2433:2440 the role of eCB metabolizing proteins and eCB receptors against oxidative stress 2433:2512 As such, our data is important for further determining the role of eCB metabolizing proteins and eCB receptors against oxidative stress. 36003139 5 51 theme acid 949:952 arg1 hydrolase 960:968 fatty acid amide hydrolase 943:968 fatty acid amide hydrolase (FAAH) 943:975 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 5 51 theme acid 949:952 arg1 FAAH 971:974 FAAH 971:974 FAAH 971:974 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 1 52 theme acid 233:236 arg1 taurine 257:263 an amino acid, neurotransmitter, taurine 224:263 taurine 257:263 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 10 53 theme proteins 2050:2057 arg1 expression 2028:2037 the expression 2024:2037 the expression of all eCB proteins tested 2024:2064 We determined that sublethal oxidative stress upregulates the expression of all eCB proteins tested. 36003139 13 54 theme metabolizing 2449:2460 arg1 proteins 2462:2469 eCB metabolizing proteins 2445:2469 eCB metabolizing proteins 2445:2469 As such, our data is important for further determining the role of eCB metabolizing proteins and eCB receptors against oxidative stress. 36003139 8 55 theme cell 1651:1654 arg1 neurons 1674:1680 primary neurons 1666:1680 primary neurons 1666:1680 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 8 55 theme cell 1651:1654 arg1 systems 1696:1702 cell model systems 1685:1702 cell model systems 1685:1702 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 8 55 theme cell 1651:1654 arg1 lines 1656:1660 transformed cell lines 1639:1660 transformed cell lines 1639:1660 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 7 56 theme cell-derived 1418:1429 arg1 cells 1431:1435 Human stem cell-derived or human neural progenitor cell-derived cells 1367:1435 cells 1431:1435 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 6 57 theme targets 1116:1122 arg1 characterization 1090:1105 Further characterization 1082:1105 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection 1082:1199 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 0 58 theme human 59:63 arg1 neurons 91:97 human neural progenitor-derived neurons 59:97 human neural progenitor-derived neurons exposed to sub-lethal oxidative stress 59:136 N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress. 36003139 7 59 theme neural 1400:1405 arg1 cells 1431:1435 Human stem cell-derived or human neural progenitor cell-derived cells 1367:1435 cells 1431:1435 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 7 60 link cell-derived 1418:1429 arg1 cells 1431:1435 Human stem cell-derived or human neural progenitor cell-derived cells 1367:1435 cells 1431:1435 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 3 61 theme physiological 527:539 arg1 processes 541:549 numerous cellular and physiological processes 505:549 numerous cellular and physiological processes 505:549 NAEs are involved in numerous cellular and physiological processes and their concentrations are elevated in response to ischemia and physical trauma to play a role in neuroprotection. 36003139 6 62 theme Further 1082:1088 arg1 characterization 1090:1105 Further characterization 1082:1105 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection 1082:1199 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 9 63 theme canonical 1880:1888 arg1 signaling 1898:1906 canonical eCB NAE signaling 1880:1906 canonical eCB NAE signaling 1880:1906 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 3 64 theme cellular 514:521 arg1 processes 541:549 numerous cellular and physiological processes 505:549 numerous cellular and physiological processes 505:549 NAEs are involved in numerous cellular and physiological processes and their concentrations are elevated in response to ischemia and physical trauma to play a role in neuroprotection. 36003139 8 65 theme cell 1685:1688 arg1 neurons 1674:1680 primary neurons 1666:1680 primary neurons 1666:1680 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 8 65 theme cell 1685:1688 arg1 systems 1696:1702 cell model systems 1685:1702 cell model systems 1685:1702 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 8 65 theme cell 1685:1688 arg1 lines 1656:1660 transformed cell lines 1639:1660 transformed cell lines 1639:1660 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 9 66 theme NAE 1894:1896 arg1 signaling 1898:1906 canonical eCB NAE signaling 1880:1906 canonical eCB NAE signaling 1880:1906 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 1 67 theme acyl 201:204 arg1 group 206:210 an acyl group 198:210 an acyl group N-linked to an amino acid, neurotransmitter, taurine 198:263 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 6 68 theme neurodegeneration 1163:1179 arg1 system 1153:1158 a more contemporary model system 1127:1158 a more contemporary model system of neurodegeneration and neuroprotection 1127:1199 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 1 69 theme N-acyl 139:144 arg1 NAAs 154:157 NAAs 154:157 NAAs 154:157 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 1 69 theme N-acyl 139:144 arg1 amides 146:151 N-acyl amides 139:151 N-acyl amides (NAAs) 139:158 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 1 69 theme N-acyl 139:144 arg1 class 166:170 a class 164:170 a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide 164:374 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 9 70 theme oxidative 1920:1928 arg1 stress 1930:1935 oxidative stress 1920:1935 oxidative stress 1920:1935 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 4 71 theme neuroprotective 672:686 arg1 properties 688:697 The neuroprotective properties 668:697 The neuroprotective properties of eCB NAEs 668:709 The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. 36003139 7 72 theme neurodegenerative 1531:1547 arg1 diseases 1549:1556 neurodegenerative diseases 1531:1556 neurodegenerative diseases 1531:1556 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 6 73 theme contemporary 1134:1145 arg1 system 1153:1158 a more contemporary model system 1127:1158 a more contemporary model system of neurodegeneration and neuroprotection 1127:1199 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 5 74 theme acid 997:1000 arg1 NAAA 1011:1014 NAAA 1011:1014 NAAA 1011:1014 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 5 74 theme acid 997:1000 arg1 amidase 1002:1008 N-acylethanolamine acid amidase 978:1008 N-acylethanolamine acid amidase (NAAA) 978:1015 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 5 75 theme targets 857:863 arg1 promising 838:846 promising 838:846 promising 838:846 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 7 76 theme development 1515:1525 arg1 study 1491:1495 the study 1487:1495 the study of human neuronal development and neurodegenerative diseases 1487:1556 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 12 77 theme first 2219:2223 arg1 study 2208:2212 This study 2203:2212 This study 2203:2212 This study is a first step toward determining how oxidative stress affects CB1, CB2, FAAH, NAAA, and NAPE-PLD expression and their potential defense against oxidative stress. 36003139 12 77 theme first 2219:2223 arg1 step 2225:2228 a first step 2217:2228 a first step toward determining how oxidative stress affects CB1, CB2, FAAH, NAAA, and NAPE-PLD expression and their potential defense against oxidative stress 2217:2375 This study is a first step toward determining how oxidative stress affects CB1, CB2, FAAH, NAAA, and NAPE-PLD expression and their potential defense against oxidative stress. 36003139 3 78 dep ischemia 604:611 arg1 response 592:599 response 592:599 response 592:599 NAEs are involved in numerous cellular and physiological processes and their concentrations are elevated in response to ischemia and physical trauma to play a role in neuroprotection. 36003139 5 79 theme cannabinoid 873:883 arg1 type 894:897 cannabinoid receptor type 1 873:899 cannabinoid receptor type 1 (CB1) 873:905 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 5 79 theme cannabinoid 873:883 arg1 CB1 902:904 CB1 902:904 CB1 902:904 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 7 80 theme human 1500:1504 arg1 development 1515:1525 human neuronal development 1500:1525 human neuronal development 1500:1525 Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. 36003139 2 81 theme multiple 444:451 arg1 types 458:462 multiple cell types 444:462 multiple cell types 444:462 These lipids are synthesized in a wide variety of organisms and in multiple cell types, including neurons. 36003139 2 81 theme multiple 444:451 arg1 neurons 475:481 neurons 475:481 neurons 475:481 These lipids are synthesized in a wide variety of organisms and in multiple cell types, including neurons. 36003139 1 82 dep taurine 257:263 arg1 neurotransmitter 239:254 an amino acid, neurotransmitter, taurine 224:263 neurotransmitter 239:254 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 36003139 0 83 theme oxidative 121:129 arg1 stress 131:136 sub-lethal oxidative stress 110:136 sub-lethal oxidative stress 110:136 N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress. 36003139 10 84 theme sublethal 1985:1993 arg1 stress 2005:2010 sublethal oxidative stress 1985:2010 sublethal oxidative stress 1985:2010 We determined that sublethal oxidative stress upregulates the expression of all eCB proteins tested. 36003139 9 85 theme ReN 1742:1744 arg1 cells 1746:1750 ReN cells 1742:1750 ReN cells 1742:1750 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 9 85 theme ReN 1742:1744 arg1 system 1775:1780 a superior cell model system 1753:1780 a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection 1753:1848 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 0 86 theme metabolizing 19:30 arg1 enzymes 32:38 N-acylethanolamide metabolizing enzymes 0:38 N-acylethanolamide metabolizing enzymes 0:38 N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress. 36003139 5 87 theme phosphatidylethanolamine 1029:1052 arg1 D 1068:1068 N-acyl phosphatidylethanolamine phospholipase D 1022:1068 N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) 1022:1079 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 2 88 theme wide 411:414 arg1 organisms 427:435 organisms 427:435 organisms 427:435 These lipids are synthesized in a wide variety of organisms and in multiple cell types, including neurons. 36003139 2 88 theme wide 411:414 arg1 variety 416:422 a wide variety 409:422 a wide variety of organisms 409:435 These lipids are synthesized in a wide variety of organisms and in multiple cell types, including neurons. 36003139 12 89 theme oxidative 2360:2368 arg1 stress 2370:2375 oxidative stress 2360:2375 oxidative stress 2360:2375 This study is a first step toward determining how oxidative stress affects CB1, CB2, FAAH, NAAA, and NAPE-PLD expression and their potential defense against oxidative stress. 36003139 4 90 theme NAEs 706:709 arg1 properties 688:697 The neuroprotective properties 668:697 The neuroprotective properties of eCB NAEs 668:709 The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. 36003139 5 91 theme cannabinoid 908:918 arg1 type 929:932 cannabinoid receptor type 2 908:934 cannabinoid receptor type 2 (CB2) 908:940 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 5 91 theme cannabinoid 908:918 arg1 CB2 937:939 CB2 937:939 CB2 937:939 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 9 92 theme superior 1755:1762 arg1 cells 1746:1750 ReN cells 1742:1750 ReN cells 1742:1750 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 9 92 theme superior 1755:1762 arg1 system 1775:1780 a superior cell model system 1753:1780 a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection 1753:1848 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 3 93 theme physical 617:624 arg1 trauma 626:631 physical trauma 617:631 physical trauma 617:631 NAEs are involved in numerous cellular and physiological processes and their concentrations are elevated in response to ischemia and physical trauma to play a role in neuroprotection. 36003139 6 94 from characterization 1090:1105 arg1 system 1153:1158 a more contemporary model system 1127:1158 a more contemporary model system of neurodegeneration and neuroprotection 1127:1199 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 5 95 theme amide 954:958 arg1 hydrolase 960:968 fatty acid amide hydrolase 943:968 fatty acid amide hydrolase (FAAH) 943:975 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 5 95 theme amide 954:958 arg1 FAAH 971:974 FAAH 971:974 FAAH 971:974 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 9 96 theme model 1769:1773 arg1 cells 1746:1750 ReN cells 1742:1750 ReN cells 1742:1750 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 9 96 theme model 1769:1773 arg1 system 1775:1780 a superior cell model system 1753:1780 a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection 1753:1848 In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. 36003139 0 97 theme neural 65:70 arg1 neurons 91:97 human neural progenitor-derived neurons 59:97 human neural progenitor-derived neurons exposed to sub-lethal oxidative stress 59:136 N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress. 36003139 6 98 from role 1239:1242 arg1 neuroprotection 1271:1285 neuroprotection 1271:1285 neuroprotection against oxidative stress leading to better utilization in the clinical setting 1271:1364 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 11 99 theme FAAH 2154:2157 arg1 localization 2138:2149 the nuclear localization 2126:2149 the nuclear localization of FAAH 2126:2157 In addition, we determined that oxidative stress increases the nuclear localization of FAAH, and to a lesser extent, NAAA and NAPE-PLD. 36003139 6 100 from mechanism 1248:1256 arg1 neuroprotection 1271:1285 neuroprotection 1271:1285 neuroprotection against oxidative stress leading to better utilization in the clinical setting 1271:1364 Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. 36003139 0 101 link progenitor-derived 72:89 arg1 neurons 91:97 human neural progenitor-derived neurons 59:97 human neural progenitor-derived neurons exposed to sub-lethal oxidative stress 59:136 N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress. 36003139 8 102 theme ReN 1559:1561 arg1 cells 1563:1567 ReN cells 1559:1567 ReN cells 1559:1567 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 4 103 theme attractive 755:764 arg1 targets 766:772 attractive targets 755:772 attractive targets for clinical intervention for a variety of conditions 755:826 The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. 36003139 5 104 theme fatty 943:947 arg1 hydrolase 960:968 fatty acid amide hydrolase 943:968 fatty acid amide hydrolase (FAAH) 943:975 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 5 104 theme fatty 943:947 arg1 FAAH 971:974 FAAH 971:974 FAAH 971:974 The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). 36003139 13 105 theme oxidative 2497:2505 arg1 stress 2507:2512 oxidative stress 2497:2512 oxidative stress 2497:2512 As such, our data is important for further determining the role of eCB metabolizing proteins and eCB receptors against oxidative stress. 36003139 8 106 theme transformed 1639:1649 arg1 neurons 1674:1680 primary neurons 1666:1680 primary neurons 1666:1680 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 8 106 theme transformed 1639:1649 arg1 systems 1696:1702 cell model systems 1685:1702 cell model systems 1685:1702 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 8 106 theme transformed 1639:1649 arg1 lines 1656:1660 transformed cell lines 1639:1660 transformed cell lines 1639:1660 ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. 36003139 1 107 theme amino 227:231 arg1 taurine 257:263 an amino acid, neurotransmitter, taurine 224:263 taurine 257:263 N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. 35749695 7 0 theme 1 1479:1479 arg1 M 1481:1481 M 1481:1481 M 1481:1481 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 5 1 from exchange 1023:1030 arg1 combination 1035:1045 combination 1035:1045 combination with mass spectrometry (HDX-MS) 1035:1077 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 7 2 theme 2-carboxyethyl 1439:1452 arg1 phosphine 1454:1462 0.4 M tris(2-carboxyethyl)phosphine 1428:1462 0.4 M tris(2-carboxyethyl)phosphine 1428:1462 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 4 3 theme tandem 665:670 arg1 spectrometry 677:688 tandem mass spectrometry 665:688 tandem mass spectrometry 665:688 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 4 4 from signal 739:744 arg1 analysis 761:768 top-down MS analysis 749:768 top-down MS analysis 749:768 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 7 5 theme M 1467:1467 arg1 urea 1469:1472 4 M urea 1465:1472 4 M urea 1465:1472 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 7 6 theme tris 1434:1437 arg1 phosphine 1454:1462 0.4 M tris(2-carboxyethyl)phosphine 1428:1462 0.4 M tris(2-carboxyethyl)phosphine 1428:1462 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 4 7 theme intact 727:732 arg1 signal 739:744 an intact mass signal 724:744 an intact mass signal in top-down MS analysis 724:768 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 5 8 theme reducing 911:918 arg1 substances 935:944 reducing and denaturing substances 911:944 reducing and denaturing substances 911:944 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 7 9 theme 0.4 1428:1430 arg1 M 1432:1432 M 1432:1432 M 1432:1432 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 8 10 from Rc 1558:1559 arg1 workflow 1574:1581 an HDX-MS workflow 1564:1581 an HDX-MS workflow 1564:1581 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 1 11 theme ubiquitous 210:219 arg1 modification 239:250 a ubiquitous posttranslational modification 208:250 a ubiquitous posttranslational modification of proteins 208:262 N-linked glycosylation is a ubiquitous posttranslational modification of proteins. 35749695 1 11 theme ubiquitous 210:219 arg1 glycosylation 191:203 N-linked glycosylation 182:203 N-linked glycosylation 182:203 N-linked glycosylation is a ubiquitous posttranslational modification of proteins. 35749695 6 12 theme broad 1190:1194 arg1 specificity 1206:1216 broad substrate specificity 1190:1216 broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins 1190:1292 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 0 13 theme Spectrometry 123:134 arg1 Mapping 144:150 Mass Spectrometry Epitope Mapping 118:150 Mass Spectrometry Epitope Mapping 118:150 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 2 14 theme proteins 328:335 arg1 function 316:323 the biological function 301:323 the biological function of proteins 301:335 While it plays an important role in the biological function of proteins, it often poses a major challenge for their analytical characterization. 35749695 8 15 theme protein 1684:1690 arg1 SIRPα 1699:1703 SIRPα 1699:1703 SIRPα 1699:1703 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 8 15 theme protein 1684:1690 arg1 alpha 1692:1696 human signal-regulating protein alpha 1660:1696 human signal-regulating protein alpha (SIRPα) 1660:1704 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 1 16 theme proteins 255:262 arg1 modification 239:250 a ubiquitous posttranslational modification 208:250 a ubiquitous posttranslational modification of proteins 208:262 N-linked glycosylation is a ubiquitous posttranslational modification of proteins. 35749695 1 16 theme proteins 255:262 arg1 glycosylation 191:203 N-linked glycosylation 182:203 N-linked glycosylation 182:203 N-linked glycosylation is a ubiquitous posttranslational modification of proteins. 35749695 0 17 theme Challenging 158:168 arg1 Conditions 170:179 Challenging Conditions 158:179 Challenging Conditions 158:179 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 5 18 theme advanced 974:981 arg1 bioanalysis 983:993 advanced bioanalysis 974:993 advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS) 974:1077 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 4 19 theme top-down 749:756 arg1 analysis 761:768 top-down MS analysis 749:768 top-down MS analysis 749:768 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 8 20 theme nanobody 1613:1620 arg1 epitope 1600:1606 the epitope 1596:1606 the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα) 1596:1704 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 5 21 theme neutral 827:833 arg1 range 857:861 the neutral to slightly acidic pH range 823:861 the neutral to slightly acidic pH range 823:861 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 1 22 theme N-linked 182:189 arg1 modification 239:250 a ubiquitous posttranslational modification 208:250 a ubiquitous posttranslational modification of proteins 208:262 N-linked glycosylation is a ubiquitous posttranslational modification of proteins. 35749695 1 22 theme N-linked 182:189 arg1 glycosylation 191:203 N-linked glycosylation 182:203 N-linked glycosylation 182:203 N-linked glycosylation is a ubiquitous posttranslational modification of proteins. 35749695 0 23 theme Improved 22:29 arg1 N-Deglycosylation 39:55 Improved Protein N-Deglycosylation 22:55 Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange 22:103 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 3 24 theme available 420:428 arg1 PNGases 452:458 PNGases 452:458 PNGases 452:458 Currently available peptide N-glycanases (PNGases) are often inefficient at deglycosylating proteins due to sterically inaccessible N-glycosylation sites. 35749695 3 24 theme available 420:428 arg1 N-glycanases 438:449 Currently available peptide N-glycanases 410:449 Currently available peptide N-glycanases (PNGases) 410:459 Currently available peptide N-glycanases (PNGases) are often inefficient at deglycosylating proteins due to sterically inaccessible N-glycosylation sites. 35749695 6 25 theme peptide 1105:1111 arg1 PNGase 1154:1159 PNGase Rc 1154:1162 PNGase Rc 1154:1162 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 6 25 theme peptide 1105:1111 arg1 N-glycanase 1113:1123 a novel peptide N-glycanase 1097:1123 a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins 1097:1292 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 0 26 theme PNGase 8:13 arg1 Rc 15:16 A Novel PNGase Rc 0:16 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange 0:103 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 6 27 theme N-glycan 1222:1229 arg1 hydrolysis 1231:1240 N-glycan hydrolysis 1222:1240 N-glycan hydrolysis from multiply occupied and natively folded proteins 1222:1292 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 5 28 theme hydrogen-deuterium 1004:1021 arg1 exchange 1023:1030 hydrogen-deuterium exchange 1004:1030 hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS) 1004:1077 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 7 29 dep conditions 1379:1388 arg1 °C 1401:1402 0 °C 1399:1402 0 °C 1399:1402 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 7 29 dep conditions 1379:1388 arg1 pH 1391:1392 pH 2.5 1391:1396 pH 2.5 1391:1396 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 7 30 theme challenging 1352:1362 arg1 conditions 1379:1388 challenging, HDX quenching conditions 1352:1388 challenging, HDX quenching conditions (pH 2.5, 0 °C) 1352:1403 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 3 31 theme N-glycosylation 542:556 arg1 sites 558:562 sterically inaccessible N-glycosylation sites 518:562 sterically inaccessible N-glycosylation sites 518:562 Currently available peptide N-glycanases (PNGases) are often inefficient at deglycosylating proteins due to sterically inaccessible N-glycosylation sites. 35749695 5 32 theme pH 854:855 arg1 range 857:861 the neutral to slightly acidic pH range 823:861 the neutral to slightly acidic pH range 823:861 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 7 33 theme chloride 1495:1502 arg1 presence 1416:1423 the presence 1412:1423 the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride 1412:1502 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 4 34 theme sequence 592:599 arg1 coverage 601:608 poor sequence coverage 587:608 poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry 587:688 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 7 35 theme M 1481:1481 arg1 chloride 1495:1502 1 M guanidinium chloride 1479:1502 1 M guanidinium chloride 1479:1502 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 7 36 dep challenging 1352:1362 arg1 HDX 1365:1367 HDX 1365:1367 HDX 1365:1367 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 4 37 theme mass 672:675 arg1 spectrometry 677:688 tandem mass spectrometry 665:688 tandem mass spectrometry 665:688 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 6 38 from cellulosilytica 1137:1151 arg1 PNGase 1154:1159 PNGase Rc 1154:1162 PNGase Rc 1154:1162 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 6 38 from cellulosilytica 1137:1151 arg1 N-glycanase 1113:1123 a novel peptide N-glycanase 1097:1123 a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins 1097:1292 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 8 39 theme extracellular 1636:1648 arg1 alpha 1692:1696 human signal-regulating protein alpha 1660:1696 human signal-regulating protein alpha (SIRPα) 1660:1704 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 8 39 theme extracellular 1636:1648 arg1 domain 1650:1655 the extracellular domain 1632:1655 the extracellular domain of human signal-regulating protein alpha (SIRPα) 1632:1704 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 0 40 gly N-Deglycosylation 39:55 arg1 Bioanalytics 60:71 Bioanalytics 60:71 Bioanalytics 60:71 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 0 40 gly N-Deglycosylation 39:55 arg1 Exchange 96:103 Hydrogen-Deuterium Exchange 77:103 Hydrogen-Deuterium Exchange 77:103 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 7 41 theme PNGase 1317:1322 arg1 Rc 1324:1325 PNGase Rc 1317:1325 PNGase Rc 1317:1325 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 7 42 theme urea 1469:1472 arg1 presence 1416:1423 the presence 1412:1423 the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride 1412:1502 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 4 43 theme liquid 638:643 arg1 chromatography 645:658 liquid chromatography 638:658 liquid chromatography 638:658 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 8 44 theme signal-regulating 1666:1682 arg1 SIRPα 1699:1703 SIRPα 1699:1703 SIRPα 1699:1703 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 8 44 theme signal-regulating 1666:1682 arg1 alpha 1692:1696 human signal-regulating protein alpha 1660:1696 human signal-regulating protein alpha (SIRPα) 1660:1704 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 7 45 theme 4 1465:1465 arg1 M 1467:1467 M 1467:1467 M 1467:1467 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 2 46 theme biological 305:314 arg1 function 316:323 the biological function 301:323 the biological function of proteins 301:335 While it plays an important role in the biological function of proteins, it often poses a major challenge for their analytical characterization. 35749695 8 47 theme alpha 1692:1696 arg1 alpha 1692:1696 human signal-regulating protein alpha 1660:1696 human signal-regulating protein alpha (SIRPα) 1660:1704 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 8 47 theme alpha 1692:1696 arg1 domain 1650:1655 the extracellular domain 1632:1655 the extracellular domain of human signal-regulating protein alpha (SIRPα) 1632:1704 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 0 48 theme Protein 31:37 arg1 N-Deglycosylation 39:55 Improved Protein N-Deglycosylation 22:55 Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange 22:103 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 7 49 theme phosphine 1454:1462 arg1 presence 1416:1423 the presence 1412:1423 the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride 1412:1502 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 7 50 theme M 1432:1432 arg1 phosphine 1454:1462 0.4 M tris(2-carboxyethyl)phosphine 1428:1462 0.4 M tris(2-carboxyethyl)phosphine 1428:1462 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 4 51 theme mass 734:737 arg1 signal 739:744 an intact mass signal 724:744 an intact mass signal in top-down MS analysis 724:768 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 0 52 theme Epitope 136:142 arg1 Mapping 144:150 Mass Spectrometry Epitope Mapping 118:150 Mass Spectrometry Epitope Mapping 118:150 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 1 53 theme posttranslational 221:237 arg1 modification 239:250 a ubiquitous posttranslational modification 208:250 a ubiquitous posttranslational modification of proteins 208:262 N-linked glycosylation is a ubiquitous posttranslational modification of proteins. 35749695 1 53 theme posttranslational 221:237 arg1 glycosylation 191:203 N-linked glycosylation 182:203 N-linked glycosylation 182:203 N-linked glycosylation is a ubiquitous posttranslational modification of proteins. 35749695 6 54 theme substrate 1196:1204 arg1 specificity 1206:1216 broad substrate specificity 1190:1216 broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins 1190:1292 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 5 55 dep neutral 827:833 arg1 acidic 847:852 acidic 847:852 acidic 847:852 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 5 55 dep neutral 827:833 arg1 to 835:836 to 835:836 to 835:836 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 5 56 with combination 1035:1045 arg1 HDX-MS 1071:1076 HDX-MS 1071:1076 HDX-MS 1071:1076 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 5 56 with combination 1035:1045 arg1 spectrometry 1057:1068 mass spectrometry 1052:1068 mass spectrometry (HDX-MS) 1052:1077 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 5 57 theme denaturing 924:933 arg1 substances 935:944 reducing and denaturing substances 911:944 reducing and denaturing substances 911:944 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 6 58 theme folded 1278:1283 arg1 proteins 1285:1292 natively folded proteins 1269:1292 natively folded proteins 1269:1292 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 6 59 from proteins 1285:1292 arg1 hydrolysis 1231:1240 N-glycan hydrolysis 1222:1240 N-glycan hydrolysis from multiply occupied and natively folded proteins 1222:1292 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 2 60 theme important 283:291 arg1 role 293:296 an important role 280:296 an important role 280:296 While it plays an important role in the biological function of proteins, it often poses a major challenge for their analytical characterization. 35749695 5 61 theme substances 935:944 arg1 presence 899:906 the presence 895:906 the presence 895:906 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 6 62 from occupied 1256:1263 arg1 hydrolysis 1231:1240 N-glycan hydrolysis 1222:1240 N-glycan hydrolysis from multiply occupied and natively folded proteins 1222:1292 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 0 63 theme Hydrogen-Deuterium 77:94 arg1 Exchange 96:103 Hydrogen-Deuterium Exchange 77:103 Hydrogen-Deuterium Exchange 77:103 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 4 64 theme MS 758:759 arg1 analysis 761:768 top-down MS analysis 749:768 top-down MS analysis 749:768 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 5 65 theme most 784:787 arg1 PNGases 789:795 most PNGases 784:795 most PNGases 784:795 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 0 66 from N-Deglycosylation 39:55 arg1 Bioanalytics 60:71 Bioanalytics 60:71 Bioanalytics 60:71 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 0 66 from N-Deglycosylation 39:55 arg1 Exchange 96:103 Hydrogen-Deuterium Exchange 77:103 Hydrogen-Deuterium Exchange 77:103 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 0 67 theme Mass 118:121 arg1 Mapping 144:150 Mass Spectrometry Epitope Mapping 118:150 Mass Spectrometry Epitope Mapping 118:150 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 6 68 theme Rudaea 1130:1135 arg1 cellulosilytica 1137:1151 Rudaea cellulosilytica 1130:1151 Rudaea cellulosilytica 1130:1151 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 0 69 theme Novel 2:6 arg1 Rc 15:16 A Novel PNGase Rc 0:16 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange 0:103 A Novel PNGase Rc for Improved Protein N-Deglycosylation in Bioanalytics and Hydrogen-Deuterium Exchange Coupled With Mass Spectrometry Epitope Mapping under Challenging Conditions. 35749695 7 70 theme quenching 1369:1377 arg1 conditions 1379:1388 challenging, HDX quenching conditions 1352:1388 challenging, HDX quenching conditions (pH 2.5, 0 °C) 1352:1403 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 3 71 theme peptide 430:436 arg1 PNGases 452:458 PNGases 452:458 PNGases 452:458 Currently available peptide N-glycanases (PNGases) are often inefficient at deglycosylating proteins due to sterically inaccessible N-glycosylation sites. 35749695 3 71 theme peptide 430:436 arg1 N-glycanases 438:449 Currently available peptide N-glycanases 410:449 Currently available peptide N-glycanases (PNGases) 410:459 Currently available peptide N-glycanases (PNGases) are often inefficient at deglycosylating proteins due to sterically inaccessible N-glycosylation sites. 35749695 4 72 theme bottom-up 613:621 arg1 analysis 623:630 bottom-up analysis 613:630 bottom-up analysis using liquid chromatography with tandem mass spectrometry 613:688 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 3 73 gly N-glycosylation 542:556 arg2 sites 558:562 sterically inaccessible N-glycosylation sites 518:562 sterically inaccessible N-glycosylation sites 518:562 Currently available peptide N-glycanases (PNGases) are often inefficient at deglycosylating proteins due to sterically inaccessible N-glycosylation sites. 35749695 6 74 theme novel 1099:1103 arg1 PNGase 1154:1159 PNGase Rc 1154:1162 PNGase Rc 1154:1162 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 6 74 theme novel 1099:1103 arg1 N-glycanase 1113:1123 a novel peptide N-glycanase 1097:1123 a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins 1097:1292 Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. 35749695 8 75 theme PNGase 1551:1556 arg1 Rc 1558:1559 the PNGase Rc 1547:1559 the PNGase Rc in an HDX-MS workflow 1547:1581 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 1 76 link N-linked 182:189 arg1 modification 239:250 a ubiquitous posttranslational modification 208:250 a ubiquitous posttranslational modification of proteins 208:262 N-linked glycosylation is a ubiquitous posttranslational modification of proteins. 35749695 1 76 link N-linked 182:189 arg1 glycosylation 191:203 N-linked glycosylation 182:203 N-linked glycosylation 182:203 N-linked glycosylation is a ubiquitous posttranslational modification of proteins. 35749695 4 77 from coverage 601:608 arg1 analysis 623:630 bottom-up analysis 613:630 bottom-up analysis using liquid chromatography with tandem mass spectrometry 613:688 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 4 78 theme poor 587:590 arg1 coverage 601:608 poor sequence coverage 587:608 poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry 587:688 This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry and makes it impossible to obtain an intact mass signal in top-down MS analysis. 35749695 8 79 theme HDX-MS 1567:1572 arg1 workflow 1574:1581 an HDX-MS workflow 1564:1581 an HDX-MS workflow 1564:1581 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 2 80 theme major 355:359 arg1 challenge 361:369 a major challenge 353:369 a major challenge for their analytical characterization 353:407 While it plays an important role in the biological function of proteins, it often poses a major challenge for their analytical characterization. 35749695 5 81 theme mass 1052:1055 arg1 HDX-MS 1071:1076 HDX-MS 1071:1076 HDX-MS 1071:1076 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 5 81 theme mass 1052:1055 arg1 spectrometry 1057:1068 mass spectrometry 1052:1068 mass spectrometry (HDX-MS) 1052:1077 In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). 35749695 3 82 theme inaccessible 529:540 arg1 sites 558:562 sterically inaccessible N-glycosylation sites 518:562 sterically inaccessible N-glycosylation sites 518:562 Currently available peptide N-glycanases (PNGases) are often inefficient at deglycosylating proteins due to sterically inaccessible N-glycosylation sites. 35749695 7 83 theme guanidinium 1483:1493 arg1 chloride 1495:1502 1 M guanidinium chloride 1479:1502 1 M guanidinium chloride 1479:1502 Our results show that PNGase Rc is functional even under challenging, HDX quenching conditions (pH 2.5, 0 °C) and in the presence of 0.4 M tris(2-carboxyethyl)phosphine, 4 M urea, and 1 M guanidinium chloride. 35749695 2 84 theme analytical 381:390 arg1 characterization 392:407 their analytical characterization 375:407 their analytical characterization 375:407 While it plays an important role in the biological function of proteins, it often poses a major challenge for their analytical characterization. 35749695 8 85 theme human 1660:1664 arg1 SIRPα 1699:1703 SIRPα 1699:1703 SIRPα 1699:1703 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 35749695 8 85 theme human 1660:1664 arg1 alpha 1692:1696 human signal-regulating protein alpha 1660:1696 human signal-regulating protein alpha (SIRPα) 1660:1704 Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα). 37239852 5 0 theme major 779:783 arg1 features 799:806 most major glyco-polymer features 774:806 most major glyco-polymer features of EVs 774:813 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 1 1 theme patho 160:164 arg1 processes 180:188 (patho)physiological processes 159:188 (patho)physiological processes 159:188 Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. 37239852 8 2 from abundance 1173:1181 arg1 EVs 1186:1188 EVs 1186:1188 EVs 1186:1188 Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. 37239852 5 3 theme glyco-polymer 785:797 arg1 features 799:806 most major glyco-polymer features 774:806 most major glyco-polymer features of EVs 774:813 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 9 4 theme hyaluronan 1353:1362 arg1 abundance 1326:1334 the differential abundance 1309:1334 the differential abundance of EV-associated hyaluronan 1309:1362 Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. 37239852 7 5 theme EV-associated 1003:1015 arg1 glyco-polymers 1017:1030 EV-associated glyco-polymers 1003:1030 EV-associated glyco-polymers that would remain undetected with conventional MS methods 1003:1088 The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. 37239852 2 6 theme glycome 368:374 arg1 analysis 376:383 comprehensive glycome analysis 354:383 comprehensive glycome analysis coupled with EV isolation 354:409 Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. 37239852 8 7 theme melanoma 1209:1216 arg1 lines 1223:1227 two different melanoma cell lines 1195:1227 two different melanoma cell lines 1195:1227 Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. 37239852 6 8 theme conventional 938:949 arg1 methods 951:957 conventional methods 938:957 conventional methods 938:957 GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. 37239852 10 9 theme biological 1496:1505 arg1 functions 1507:1515 its biological functions 1492:1515 its biological functions 1492:1515 These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions. 37239852 9 10 theme Enzyme-linked 1230:1242 arg1 assays 1258:1263 Enzyme-linked immunosorbent assays 1230:1263 Enzyme-linked immunosorbent assays 1230:1263 Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. 37239852 5 11 theme robust 742:747 arg1 approach 749:756 an innovative and robust approach 724:756 an innovative and robust approach to characterize most major glyco-polymer features of EVs 724:813 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 11 theme robust 742:747 arg1 isolation 667:675 tangential flow filtration-based EV isolation 631:675 tangential flow filtration-based EV isolation 631:675 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 12 theme glycan 694:699 arg1 GNA 716:718 GNA 716:718 GNA 716:718 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 12 theme glycan 694:699 arg1 analysis 706:713 glycan node analysis 694:713 glycan node analysis (GNA) 694:719 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 3 13 theme N-linked 498:505 arg1 glycans 507:513 N-linked glycans 498:513 N-linked glycans 498:513 Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. 37239852 2 14 theme comprehensive 354:366 arg1 analysis 376:383 comprehensive glycome analysis 354:383 comprehensive glycome analysis coupled with EV isolation 354:409 Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. 37239852 5 15 theme flow 642:645 arg1 approach 749:756 an innovative and robust approach 724:756 an innovative and robust approach to characterize most major glyco-polymer features of EVs 724:813 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 15 theme flow 642:645 arg1 isolation 667:675 tangential flow filtration-based EV isolation 631:675 tangential flow filtration-based EV isolation 631:675 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 16 theme tangential 631:640 arg1 approach 749:756 an innovative and robust approach 724:756 an innovative and robust approach to characterize most major glyco-polymer features of EVs 724:813 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 16 theme tangential 631:640 arg1 isolation 667:675 tangential flow filtration-based EV isolation 631:675 tangential flow filtration-based EV isolation 631:675 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 1 17 theme physiological 166:178 arg1 processes 180:188 (patho)physiological processes 159:188 (patho)physiological processes 159:188 Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. 37239852 8 18 theme cell 1218:1221 arg1 lines 1223:1227 two different melanoma cell lines 1195:1227 two different melanoma cell lines 1195:1227 Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. 37239852 5 19 theme filtration-based 647:662 arg1 approach 749:756 an innovative and robust approach 724:756 an innovative and robust approach to characterize most major glyco-polymer features of EVs 724:813 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 19 theme filtration-based 647:662 arg1 isolation 667:675 tangential flow filtration-based EV isolation 631:675 tangential flow filtration-based EV isolation 631:675 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 3 20 theme Conventional 412:423 arg1 spectrometry 430:441 Conventional mass spectrometry 412:441 Conventional mass spectrometry (MS)-based methods 412:460 Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. 37239852 3 20 theme Conventional 412:423 arg1 MS 444:445 MS 444:445 MS 444:445 Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. 37239852 0 21 theme Node 7:10 arg1 Analysis 12:19 Glycan Node Analysis 0:19 Glycan Node Analysis 0:19 Glycan Node Analysis Detects Varying Glycosaminoglycan Levels in Melanoma-Derived Extracellular Vesicles. 37239852 5 22 theme EV 664:665 arg1 approach 749:756 an innovative and robust approach 724:756 an innovative and robust approach to characterize most major glyco-polymer features of EVs 724:813 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 22 theme EV 664:665 arg1 isolation 667:675 tangential flow filtration-based EV isolation 631:675 tangential flow filtration-based EV isolation 631:675 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 9 23 theme enzymatic 1269:1277 arg1 protocols 1289:1297 enzymatic stripping protocols 1269:1297 enzymatic stripping protocols 1269:1297 Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. 37239852 1 24 theme Extracellular 106:118 arg1 vesicles 120:127 Extracellular vesicles 106:127 Extracellular vesicles (EVs) 106:133 Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. 37239852 1 24 theme Extracellular 106:118 arg1 EVs 130:132 EVs 130:132 EVs 130:132 Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. 37239852 0 25 theme Glycan 0:5 arg1 Analysis 12:19 Glycan Node Analysis 0:19 Glycan Node Analysis 0:19 Glycan Node Analysis Detects Varying Glycosaminoglycan Levels in Melanoma-Derived Extracellular Vesicles. 37239852 9 26 theme stripping 1279:1287 arg1 protocols 1289:1297 enzymatic stripping protocols 1269:1297 enzymatic stripping protocols 1269:1297 Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. 37239852 3 27 theme -based 447:452 arg1 methods 454:460 Conventional mass spectrometry (MS)-based methods 412:460 Conventional mass spectrometry (MS)-based methods 412:460 Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. 37239852 10 28 theme EV 1475:1476 arg1 glycocode 1478:1486 the EV glycocode 1471:1486 the EV glycocode 1471:1486 These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions. 37239852 5 29 theme EVs 811:813 arg1 features 799:806 most major glyco-polymer features 774:806 most major glyco-polymer features of EVs 774:813 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 1 30 theme cell 203:206 arg1 communication 208:220 cell communication 203:220 cell communication 203:220 Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. 37239852 4 31 from classes 580:586 arg1 EVs 591:593 EVs 591:593 EVs 591:593 Therefore, methods to comprehensively analyze all glyco-polymer classes on EVs are urgently needed. 37239852 8 32 theme different 1199:1207 arg1 lines 1223:1227 two different melanoma cell lines 1195:1227 two different melanoma cell lines 1195:1227 Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. 37239852 6 33 with unobtainable 920:931 arg1 methods 951:957 conventional methods 938:957 conventional methods 938:957 GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. 37239852 0 34 theme Glycosaminoglycan 37:53 arg1 Levels 55:60 Varying Glycosaminoglycan Levels 29:60 Varying Glycosaminoglycan Levels 29:60 Glycan Node Analysis Detects Varying Glycosaminoglycan Levels in Melanoma-Derived Extracellular Vesicles. 37239852 6 35 theme unique 893:898 arg1 information 900:910 unique information 893:910 unique information that is unobtainable with conventional methods 893:957 GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. 37239852 2 36 theme EV 398:399 arg1 isolation 401:409 EV isolation 398:409 EV isolation 398:409 Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. 37239852 10 37 from classes 1445:1451 arg1 EVs 1456:1458 EVs 1456:1458 EVs 1456:1458 These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions. 37239852 0 38 theme Varying 29:35 arg1 Levels 55:60 Varying Glycosaminoglycan Levels 29:60 Varying Glycosaminoglycan Levels 29:60 Glycan Node Analysis Detects Varying Glycosaminoglycan Levels in Melanoma-Derived Extracellular Vesicles. 37239852 5 39 theme innovative 727:736 arg1 approach 749:756 an innovative and robust approach 724:756 an innovative and robust approach to characterize most major glyco-polymer features of EVs 724:813 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 39 theme innovative 727:736 arg1 isolation 667:675 tangential flow filtration-based EV isolation 631:675 tangential flow filtration-based EV isolation 631:675 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 9 40 theme differential 1313:1324 arg1 abundance 1326:1334 the differential abundance 1309:1334 the differential abundance of EV-associated hyaluronan 1309:1362 Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. 37239852 7 41 theme MS 1079:1080 arg1 methods 1082:1088 conventional MS methods 1066:1088 conventional MS methods 1066:1088 The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. 37239852 3 42 theme mass 425:428 arg1 spectrometry 430:441 Conventional mass spectrometry 412:441 Conventional mass spectrometry (MS)-based methods 412:460 Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. 37239852 3 42 theme mass 425:428 arg1 MS 444:445 MS 444:445 MS 444:445 Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. 37239852 4 43 dep methods 527:533 arg1 analyze 554:560 analyze 554:560 to comprehensively analyze all glyco-polymer classes on EVs 535:593 Therefore, methods to comprehensively analyze all glyco-polymer classes on EVs are urgently needed. 37239852 5 44 theme node 701:704 arg1 GNA 716:718 GNA 716:718 GNA 716:718 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 44 theme node 701:704 arg1 analysis 706:713 glycan node analysis 694:713 glycan node analysis (GNA) 694:719 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 5 45 theme most 774:777 arg1 features 799:806 most major glyco-polymer features 774:806 most major glyco-polymer features of EVs 774:813 In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. 37239852 9 46 link Enzyme-linked 1230:1242 arg1 assays 1258:1263 Enzyme-linked immunosorbent assays 1230:1263 Enzyme-linked immunosorbent assays 1230:1263 Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. 37239852 3 47 theme glycans 507:513 arg1 assessment 484:493 the assessment 480:493 the assessment of N-linked glycans 480:513 Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. 37239852 3 48 theme spectrometry 430:441 arg1 methods 454:460 Conventional mass spectrometry (MS)-based methods 412:460 Conventional mass spectrometry (MS)-based methods 412:460 Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. 37239852 4 49 theme glyco-polymer 566:578 arg1 classes 580:586 all glyco-polymer classes 562:586 all glyco-polymer classes on EVs 562:593 Therefore, methods to comprehensively analyze all glyco-polymer classes on EVs are urgently needed. 37239852 3 50 link N-linked 498:505 arg1 glycans 507:513 N-linked glycans 498:513 N-linked glycans 498:513 Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. 37239852 9 51 theme EV-associated 1339:1351 arg1 hyaluronan 1353:1362 EV-associated hyaluronan 1339:1362 EV-associated hyaluronan 1339:1362 Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. 37239852 6 52 theme chromatography-MS 851:867 arg1 technique 869:877 a molecularly bottom-up gas chromatography-MS technique 823:877 a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods 823:957 GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. 37239852 6 52 theme chromatography-MS 851:867 arg1 GNA 816:818 GNA 816:818 GNA 816:818 GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. 37239852 7 53 theme conventional 1066:1077 arg1 methods 1082:1088 conventional MS methods 1066:1088 conventional MS methods 1066:1088 The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. 37239852 1 54 theme important 140:148 arg1 roles 150:154 important roles 140:154 important roles 140:154 Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. 37239852 6 55 theme gas 847:849 arg1 technique 869:877 a molecularly bottom-up gas chromatography-MS technique 823:877 a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods 823:957 GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. 37239852 6 55 theme gas 847:849 arg1 GNA 816:818 GNA 816:818 GNA 816:818 GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. 37239852 2 56 theme technical 330:338 arg1 challenges 340:349 technical challenges 330:349 technical challenges 330:349 Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. 37239852 2 57 contain contain 236:242 arg1 EVs 232:234 EVs 232:234 EVs 232:234 Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. 37239852 2 57 contain contain 236:242 arg2 GAGs 276:279 GAGs 276:279 GAGs 276:279 Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. 37239852 2 57 contain contain 236:242 arg2 glycosaminoglycans 256:273 glycosaminoglycans 256:273 glycosaminoglycans (GAGs) 256:280 Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. 37239852 2 57 contain contain 236:242 arg2 glycans 244:250 glycans 244:250 glycans 244:250 Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. 37239852 0 58 theme Extracellular 82:94 arg1 Vesicles 96:103 Melanoma-Derived Extracellular Vesicles 65:103 Melanoma-Derived Extracellular Vesicles 65:103 Glycan Node Analysis Detects Varying Glycosaminoglycan Levels in Melanoma-Derived Extracellular Vesicles. 37239852 6 59 theme bottom-up 837:845 arg1 technique 869:877 a molecularly bottom-up gas chromatography-MS technique 823:877 a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods 823:957 GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. 37239852 6 59 theme bottom-up 837:845 arg1 GNA 816:818 GNA 816:818 GNA 816:818 GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. 37239852 10 60 theme glycan 1438:1443 arg1 classes 1445:1451 major glycan classes 1432:1451 major glycan classes on EVs 1432:1458 These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions. 37239852 9 61 dep Enzyme-linked 1230:1242 arg1 immunosorbent 1244:1256 immunosorbent 1244:1256 immunosorbent 1244:1256 Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. 37239852 0 62 theme Melanoma-Derived 65:80 arg1 Vesicles 96:103 Melanoma-Derived Extracellular Vesicles 65:103 Melanoma-Derived Extracellular Vesicles 65:103 Glycan Node Analysis Detects Varying Glycosaminoglycan Levels in Melanoma-Derived Extracellular Vesicles. 37239852 10 63 theme major 1432:1436 arg1 classes 1445:1451 major glycan classes 1432:1451 major glycan classes on EVs 1432:1458 These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions. 37239852 7 64 with undetected 1050:1059 arg1 methods 1082:1088 conventional MS methods 1066:1088 conventional MS methods 1066:1088 The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. 36945431 5 0 theme ADP-ribose 653:662 arg1 DNA 718:720 DNA 718:720 DNA 718:720 ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell's biological processes. 36945431 5 0 theme ADP-ribose 653:662 arg1 moiety 664:669 the ADP-ribose moiety 649:669 the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins 649:715 ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell's biological processes. 36945431 5 0 theme ADP-ribose 653:662 arg1 RNA 723:725 RNA 723:725 RNA 723:725 ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell's biological processes. 36945431 3 1 contain contains 407:414 arg2 macrodomains 416:427 macrodomains 416:427 macrodomains 416:427 Among these Nsp proteins, Nsp3 contains macrodomains, e.g., Mac1, Mac2, Mac3, with potential effects on host cells. 36945431 3 1 contain contains 407:414 arg1 Nsp3 402:405 Nsp3 402:405 Nsp3 402:405 Among these Nsp proteins, Nsp3 contains macrodomains, e.g., Mac1, Mac2, Mac3, with potential effects on host cells. 36945431 4 2 theme mammalian 586:594 arg1 cells 596:600 mammalian cells 586:600 mammalian cells 586:600 Mac1 has been shown to increase SARS-CoV-2 virulence and disrupt ADP-ribosylation pathways in mammalian cells. 36945431 13 3 theme N-linked 1689:1696 arg1 groups 1709:1714 N-linked functional groups 1689:1714 N-linked functional groups 1689:1714 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 22 4 theme ADP-ribosylation 2673:2688 arg1 pathways 2690:2697 host-mediated ADP-ribosylation pathways 2659:2697 host-mediated ADP-ribosylation pathways 2659:2697 These data suggest that Mac1 may have multi-function as a α-NAD + consumer for viral replication and a disruptor of host-mediated ADP-ribosylation pathways. 36945431 9 5 theme hydrolytic 1177:1186 arg1 activities 1188:1197 potential hydrolytic activities 1167:1197 potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose 1167:1262 Here, we examined potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose. 36945431 6 6 theme Pseudomonas 846:856 arg1 toxins 858:863 Pseudomonas toxins 846:863 Pseudomonas toxins 846:863 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 6 6 theme Pseudomonas 846:856 arg1 toxins 832:837 bacterial toxins 822:837 bacterial toxins 822:837 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 2 7 theme non-structural 281:294 arg1 virus 259:263 The virus 255:263 The virus 255:263 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 2 7 theme non-structural 281:294 arg1 Nsps 306:309 Nsps 306:309 Nsps 306:309 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 2 7 theme non-structural 281:294 arg1 proteins 296:303 several non-structural proteins 273:303 several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes 273:373 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 1 8 theme global 184:189 arg1 pandemic 191:198 a global pandemic 182:198 a global pandemic that resulted in more than 6-million deaths worldwide 182:252 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36945431 9 9 theme Mac1 1213:1216 arg1 activities 1188:1197 potential hydrolytic activities 1167:1197 potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose 1167:1262 Here, we examined potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose. 36945431 19 10 theme multiple 2313:2320 arg1 activities 2322:2331 multiple activities 2313:2331 multiple activities 2313:2331 Here we report that Mac1, but not Mac2 and Mac3, has multiple activities, i.e., Mac1 hydrolyzed. 36945431 10 11 with consistent 1306:1315 arg1 stereospecificity 1322:1338 stereospecificity 1322:1338 stereospecificity 1322:1338 Mac1 cleaved α-NAD + , but not β-NAD + , consistent with stereospecificity at the C-1" bond. 36945431 9 12 theme 2 1219:1219 arg1 activities 1188:1197 potential hydrolytic activities 1167:1197 potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose 1167:1262 Here, we examined potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose. 36945431 6 13 theme signaling 921:929 arg1 pathways 931:938 protein biosynthetic and signaling pathways 896:938 pathways 931:938 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 22 14 contain have 2576:2579 arg1 Mac1 2567:2570 Mac1 2567:2570 Mac1 2567:2570 These data suggest that Mac1 may have multi-function as a α-NAD + consumer for viral replication and a disruptor of host-mediated ADP-ribosylation pathways. 36945431 22 14 contain have 2576:2579 arg2 disruptor 2646:2654 a disruptor 2644:2654 a disruptor of host-mediated ADP-ribosylation pathways 2644:2697 These data suggest that Mac1 may have multi-function as a α-NAD + consumer for viral replication and a disruptor of host-mediated ADP-ribosylation pathways. 36945431 22 14 contain have 2576:2579 arg2 multi-function 2581:2594 multi-function 2581:2594 multi-function 2581:2594 These data suggest that Mac1 may have multi-function as a α-NAD + consumer for viral replication and a disruptor of host-mediated ADP-ribosylation pathways. 36945431 21 15 from ADP-ribose-serine 2433:2449 arg1 peptide 2466:2472 a histone 3 peptide 2454:2472 a histone 3 peptide (aa1-21) 2454:2481 However, Mac1 did not hydrolyze β-NAD + , ADP-ribose-serine on a histone 3 peptide (aa1-21), and ADP-ribose-arginine, exhibiting substrate selectivity. 36945431 21 15 from ADP-ribose-serine 2433:2449 arg1 aa1-21 2475:2480 aa1-21 2475:2480 aa1-21 2475:2480 However, Mac1 did not hydrolyze β-NAD + , ADP-ribose-serine on a histone 3 peptide (aa1-21), and ADP-ribose-arginine, exhibiting substrate selectivity. 36945431 21 16 theme histone 2456:2462 arg1 peptide 2466:2472 a histone 3 peptide 2454:2472 a histone 3 peptide (aa1-21) 2454:2481 However, Mac1 did not hydrolyze β-NAD + , ADP-ribose-serine on a histone 3 peptide (aa1-21), and ADP-ribose-arginine, exhibiting substrate selectivity. 36945431 21 16 theme histone 2456:2462 arg1 aa1-21 2475:2480 aa1-21 2475:2480 aa1-21 2475:2480 However, Mac1 did not hydrolyze β-NAD + , ADP-ribose-serine on a histone 3 peptide (aa1-21), and ADP-ribose-arginine, exhibiting substrate selectivity. 36945431 19 17 dep Mac1 2340:2343 arg1 i.e. 2334:2337 i.e. 2334:2337 i.e. 2334:2337 Here we report that Mac1, but not Mac2 and Mac3, has multiple activities, i.e., Mac1 hydrolyzed. 36945431 13 18 theme α-ADP-ribose- 1559:1571 arg1 arginine 1573:1580 α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide 1559:1624 arginine 1573:1580 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 5 19 dep proteins 708:715 arg1 e.g. 702:705 e.g. 702:705 e.g. 702:705 ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell's biological processes. 36945431 15 20 theme SARS-CoV-2 1950:1959 arg1 targets 1973:1979 potential SARS-CoV-2 therapeutic targets 1940:1979 potential SARS-CoV-2 therapeutic targets 1940:1979 New insights on Nsp3 activities may shed light on potential SARS-CoV-2 therapeutic targets. 36945431 5 21 theme various 683:689 arg1 acceptors 691:699 various acceptors 683:699 various acceptors 683:699 ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell's biological processes. 36945431 13 22 theme catalytic 1741:1749 arg1 site 1751:1754 the catalytic site 1737:1754 the catalytic site in the ADP-ribose moiety 1737:1779 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 0 23 theme Diverse 66:72 arg1 Substrates 90:99 Diverse ADP-ribosylated Substrates 66:99 Diverse ADP-ribosylated Substrates 66:99 Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 Hydrolyzes Diverse ADP-ribosylated Substrates. 36945431 19 24 contain has 2309:2311 arg2 activities 2322:2331 multiple activities 2313:2331 multiple activities 2313:2331 Here we report that Mac1, but not Mac2 and Mac3, has multiple activities, i.e., Mac1 hydrolyzed. 36945431 19 24 contain has 2309:2311 arg1 Mac1 2280:2283 Mac1 2280:2283 Mac1 2280:2283 Here we report that Mac1, but not Mac2 and Mac3, has multiple activities, i.e., Mac1 hydrolyzed. 36945431 19 24 contain has 2309:2311 arg1 Mac2 2294:2297 Mac2 2294:2297 Mac2 2294:2297 Here we report that Mac1, but not Mac2 and Mac3, has multiple activities, i.e., Mac1 hydrolyzed. 36945431 13 25 theme -histone 1606:1613 arg1 peptide 1618:1624 α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide 1559:1624 peptide 1618:1624 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 21 26 theme substrate 2520:2528 arg1 selectivity 2530:2540 substrate selectivity 2520:2540 substrate selectivity 2520:2540 However, Mac1 did not hydrolyze β-NAD + , ADP-ribose-serine on a histone 3 peptide (aa1-21), and ADP-ribose-arginine, exhibiting substrate selectivity. 36945431 9 27 contain containing 1242:1251 arg2 ADP-ribose 1253:1262 ADP-ribose 1253:1262 ADP-ribose 1253:1262 Here, we examined potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose. 36945431 9 27 contain containing 1242:1251 arg1 substrates 1231:1240 substrates 1231:1240 substrates containing ADP-ribose 1231:1262 Here, we examined potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose. 36945431 16 28 dep proteins 2130:2137 arg1 3 2139:2139 3 2139:2139 3 2139:2139 IMPORTANCE SARS-CoV-2, the virus responsible for COVID-19, encodes 3 macrodomain-containing proteins, e.g., Mac1, Mac2, Mac3, within non-structural proteins 3 (Nsp3). 36945431 16 28 dep proteins 2130:2137 arg1 Nsp3 2142:2145 Nsp3 2142:2145 Nsp3 2142:2145 IMPORTANCE SARS-CoV-2, the virus responsible for COVID-19, encodes 3 macrodomain-containing proteins, e.g., Mac1, Mac2, Mac3, within non-structural proteins 3 (Nsp3). 36945431 12 29 theme O 1458:1458 arg1 -acetyl-ADP-ribose 1460:1477 O -acetyl-ADP-ribose 1458:1477 O -acetyl-ADP-ribose 1458:1477 Mac1 also hydrolyzed O -acetyl-ADP-ribose and ADP-ribose-1"-phosphat, but not Mac2 and Mac3. 36945431 10 30 theme " 1350:1350 arg1 bond 1352:1355 the C-1" bond 1343:1355 the C-1" bond 1343:1355 Mac1 cleaved α-NAD + , but not β-NAD + , consistent with stereospecificity at the C-1" bond. 36945431 1 31 theme syndrome 127:134 arg1 coronavirus 136:146 Severe acute respiratory syndrome coronavirus 2 102:148 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 102:161 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36945431 1 31 theme syndrome 127:134 arg1 SARS-CoV-2 151:160 SARS-CoV-2 151:160 SARS-CoV-2 151:160 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36945431 23 32 theme possible 2766:2773 arg1 targets 2787:2793 possible therapeutic targets 2766:2793 possible therapeutic targets for COVID-19 2766:2806 Understanding Mac1's mechanisms of action is important to provide possible therapeutic targets for COVID-19. 36945431 13 33 theme ADP-ribose- 1587:1597 arg1 peptide 1618:1624 α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide 1559:1624 peptide 1618:1624 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 13 34 theme ADP-ribose 1763:1772 arg1 moiety 1774:1779 the ADP-ribose moiety 1759:1779 the ADP-ribose moiety 1759:1779 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 13 35 link N-linked 1689:1696 arg1 groups 1709:1714 N-linked functional groups 1689:1714 N-linked functional groups 1689:1714 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 13 36 theme serine 1599:1604 arg1 peptide 1618:1624 α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide 1559:1624 peptide 1618:1624 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 0 37 theme Macrodomain 0:10 arg1 Mac1 12:15 Macrodomain Mac1 0:15 Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 0:53 Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 Hydrolyzes Diverse ADP-ribosylated Substrates. 36945431 1 38 theme acute 109:113 arg1 coronavirus 136:146 Severe acute respiratory syndrome coronavirus 2 102:148 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 102:161 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36945431 1 38 theme acute 109:113 arg1 SARS-CoV-2 151:160 SARS-CoV-2 151:160 SARS-CoV-2 151:160 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36945431 3 39 theme Nsp 388:390 arg1 proteins 392:399 these Nsp proteins 382:399 these Nsp proteins 382:399 Among these Nsp proteins, Nsp3 contains macrodomains, e.g., Mac1, Mac2, Mac3, with potential effects on host cells. 36945431 4 40 theme SARS-CoV-2 524:533 arg1 virulence 535:543 SARS-CoV-2 virulence 524:543 SARS-CoV-2 virulence 524:543 Mac1 has been shown to increase SARS-CoV-2 virulence and disrupt ADP-ribosylation pathways in mammalian cells. 36945431 11 41 theme Mg 1409:1410 arg1 2+ 1412:1413 Mg 2+ 1409:1413 Mg 2+ 1409:1413 In contrast to ARH1 and ARH3, Mac1 did not require Mg 2+ for optimal activity. 36945431 16 42 dep Mac1 2090:2093 arg1 e.g. 2084:2087 e.g. 2084:2087 e.g. 2084:2087 IMPORTANCE SARS-CoV-2, the virus responsible for COVID-19, encodes 3 macrodomain-containing proteins, e.g., Mac1, Mac2, Mac3, within non-structural proteins 3 (Nsp3). 36945431 15 43 theme therapeutic 1961:1971 arg1 targets 1973:1979 potential SARS-CoV-2 therapeutic targets 1940:1979 potential SARS-CoV-2 therapeutic targets 1940:1979 New insights on Nsp3 activities may shed light on potential SARS-CoV-2 therapeutic targets. 36945431 18 44 theme viral 2239:2243 arg1 proliferation 2245:2257 viral proliferation 2239:2257 viral proliferation 2239:2257 Inactivation of Mac1 reduced viral proliferation. 36945431 0 45 theme Nonstructural 31:43 arg1 Protein 45:51 SARS-CoV-2 Nonstructural Protein 3 20:53 SARS-CoV-2 Nonstructural Protein 3 20:53 Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 Hydrolyzes Diverse ADP-ribosylated Substrates. 36945431 6 46 theme bacterial 822:830 arg1 toxin 877:881 diphtheria toxin 866:881 diphtheria toxin that disrupt protein biosynthetic and signaling pathways 866:938 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 6 46 theme bacterial 822:830 arg1 toxins 858:863 Pseudomonas toxins 846:863 Pseudomonas toxins 846:863 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 6 46 theme bacterial 822:830 arg1 toxins 832:837 bacterial toxins 822:837 bacterial toxins 822:837 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 3 47 dep Mac1 436:439 arg1 e.g. 430:433 e.g. 430:433 e.g. 430:433 Among these Nsp proteins, Nsp3 contains macrodomains, e.g., Mac1, Mac2, Mac3, with potential effects on host cells. 36945431 18 48 theme Mac1 2226:2229 arg1 Inactivation 2210:2221 Inactivation 2210:2221 Inactivation of Mac1 2210:2229 Inactivation of Mac1 reduced viral proliferation. 36945431 22 49 theme viral 2622:2626 arg1 replication 2628:2638 viral replication 2622:2638 viral replication 2622:2638 These data suggest that Mac1 may have multi-function as a α-NAD + consumer for viral replication and a disruptor of host-mediated ADP-ribosylation pathways. 36945431 2 50 theme cellular 356:363 arg1 processes 365:373 cellular processes 356:373 cellular processes 356:373 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 5 51 theme biological 753:762 arg1 processes 764:772 a cell's biological processes 744:772 a cell's biological processes 744:772 ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell's biological processes. 36945431 2 52 contain contain 317:323 arg2 elements 325:332 elements 325:332 elements capable of disrupting cellular processes 325:373 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 2 52 contain contain 317:323 arg1 virus 259:263 The virus 255:263 The virus 255:263 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 2 52 contain contain 317:323 arg1 Nsps 306:309 Nsps 306:309 Nsps 306:309 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 2 52 contain contain 317:323 arg1 proteins 296:303 several non-structural proteins 273:303 several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes 273:373 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 8 53 theme macrodomain-containing 1069:1090 arg1 proteins 1092:1099 the macrodomain-containing proteins 1065:1099 the macrodomain-containing proteins 1065:1099 By this reaction, the macrodomain-containing proteins interfere ADP-ribose homeostasis in host cells. 36945431 6 54 theme action 812:817 arg1 ADP-ribosylation 775:790 ADP-ribosylation 775:790 ADP-ribosylation 775:790 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 6 54 theme action 812:817 arg1 mechanism 799:807 the mechanism 795:807 the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways 795:938 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 6 55 dep toxins 832:837 arg1 e.g. 840:843 bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways 822:938 e.g. 840:843 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 3 56 theme potential 459:467 arg1 effects 469:475 potential effects 459:475 potential effects on host cells 459:489 Among these Nsp proteins, Nsp3 contains macrodomains, e.g., Mac1, Mac2, Mac3, with potential effects on host cells. 36945431 1 57 theme 6-million 227:235 arg1 worldwide 244:252 6-million deaths worldwide 227:252 6-million deaths worldwide 227:252 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36945431 16 58 theme responsible 2015:2025 arg1 virus 2009:2013 the virus 2005:2013 the virus responsible for COVID-19 2005:2038 IMPORTANCE SARS-CoV-2, the virus responsible for COVID-19, encodes 3 macrodomain-containing proteins, e.g., Mac1, Mac2, Mac3, within non-structural proteins 3 (Nsp3). 36945431 16 58 theme responsible 2015:2025 arg1 IMPORTANCE 1982:1991 IMPORTANCE SARS-CoV-2 1982:2002 IMPORTANCE SARS-CoV-2 1982:2002 IMPORTANCE SARS-CoV-2, the virus responsible for COVID-19, encodes 3 macrodomain-containing proteins, e.g., Mac1, Mac2, Mac3, within non-structural proteins 3 (Nsp3). 36945431 16 59 theme non-structural 2115:2128 arg1 proteins 2130:2137 non-structural proteins 3 (Nsp3) 2115:2146 non-structural proteins 3 (Nsp3) 2115:2146 IMPORTANCE SARS-CoV-2, the virus responsible for COVID-19, encodes 3 macrodomain-containing proteins, e.g., Mac1, Mac2, Mac3, within non-structural proteins 3 (Nsp3). 36945431 8 60 theme host 1137:1140 arg1 cells 1142:1146 host cells 1137:1146 host cells 1137:1146 By this reaction, the macrodomain-containing proteins interfere ADP-ribose homeostasis in host cells. 36945431 6 61 theme diphtheria 866:875 arg1 toxins 832:837 bacterial toxins 822:837 bacterial toxins 822:837 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 6 61 theme diphtheria 866:875 arg1 toxin 877:881 diphtheria toxin 866:881 diphtheria toxin that disrupt protein biosynthetic and signaling pathways 866:938 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 4 62 theme ADP-ribosylation 557:572 arg1 pathways 574:581 ADP-ribosylation pathways 557:581 ADP-ribosylation pathways in mammalian cells 557:600 Mac1 has been shown to increase SARS-CoV-2 virulence and disrupt ADP-ribosylation pathways in mammalian cells. 36945431 3 63 from effects 469:475 arg1 cells 485:489 host cells 480:489 host cells 480:489 Among these Nsp proteins, Nsp3 contains macrodomains, e.g., Mac1, Mac2, Mac3, with potential effects on host cells. 36945431 5 64 theme moiety 664:669 arg1 transfer 637:644 the transfer 633:644 the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA 633:725 ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell's biological processes. 36945431 9 65 theme potential 1167:1175 arg1 activities 1188:1197 potential hydrolytic activities 1167:1197 potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose 1167:1262 Here, we examined potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose. 36945431 13 66 theme functional 1698:1707 arg1 groups 1709:1714 N-linked functional groups 1689:1714 N-linked functional groups 1689:1714 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 22 67 theme host-mediated 2659:2671 arg1 pathways 2690:2697 host-mediated ADP-ribosylation pathways 2659:2697 host-mediated ADP-ribosylation pathways 2659:2697 These data suggest that Mac1 may have multi-function as a α-NAD + consumer for viral replication and a disruptor of host-mediated ADP-ribosylation pathways. 36945431 10 68 theme C-1 1347:1349 arg1 bond 1352:1355 the C-1" bond 1343:1355 the C-1" bond 1343:1355 Mac1 cleaved α-NAD + , but not β-NAD + , consistent with stereospecificity at the C-1" bond. 36945431 14 69 theme anti-viral 1825:1834 arg1 activity 1836:1843 anti-viral activity 1825:1843 anti-viral activity 1825:1843 We conclude that SARS-CoV-2 Mac1 may exert anti-viral activity by reversing host-mediated ADP-ribosylation. 36945431 9 70 theme SARS-CoV-2 1202:1211 arg1 Mac1 1213:1216 SARS-CoV-2 Mac1 1202:1216 SARS-CoV-2 Mac1 1202:1216 Here, we examined potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose. 36945431 13 71 attach attached 1670:1677 arg1 groups 1709:1714 N-linked functional groups 1689:1714 N-linked functional groups 1689:1714 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 13 71 attach attached 1670:1677 arg2 ADP-ribose 1659:1668 ADP-ribose 1659:1668 ADP-ribose attached to O- and N-linked functional groups 1659:1714 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 13 71 attach attached 1670:1677 arg1 O- 1682:1683 O- 1682:1683 O- 1682:1683 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 14 72 theme SARS-CoV-2 1799:1808 arg1 Mac1 1810:1813 SARS-CoV-2 Mac1 1799:1813 SARS-CoV-2 Mac1 1799:1813 We conclude that SARS-CoV-2 Mac1 may exert anti-viral activity by reversing host-mediated ADP-ribosylation. 36945431 15 73 theme New 1890:1892 arg1 insights 1894:1901 New insights 1890:1901 New insights on Nsp3 activities 1890:1920 New insights on Nsp3 activities may shed light on potential SARS-CoV-2 therapeutic targets. 36945431 7 74 theme free 1030:1033 arg1 ADP-ribose 1035:1044 free ADP-ribose 1030:1044 free ADP-ribose 1030:1044 On the other hand, some viral macrodomains cleavage ADP-ribose-acceptor bond, generating free ADP-ribose. 36945431 5 75 theme NAD 674:676 arg1 DNA 718:720 DNA 718:720 DNA 718:720 ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell's biological processes. 36945431 5 75 theme NAD 674:676 arg1 moiety 664:669 the ADP-ribose moiety 649:669 the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins 649:715 ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell's biological processes. 36945431 5 75 theme NAD 674:676 arg1 RNA 723:725 RNA 723:725 RNA 723:725 ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD + to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell's biological processes. 36945431 9 76 theme 3 1226:1226 arg1 activities 1188:1197 potential hydrolytic activities 1167:1197 potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose 1167:1262 Here, we examined potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose. 36945431 7 77 theme cleavage 984:991 arg1 bond 1013:1016 cleavage ADP-ribose-acceptor bond 984:1016 cleavage ADP-ribose-acceptor bond 984:1016 On the other hand, some viral macrodomains cleavage ADP-ribose-acceptor bond, generating free ADP-ribose. 36945431 11 78 theme optimal 1419:1425 arg1 activity 1427:1434 optimal activity 1419:1434 optimal activity 1419:1434 In contrast to ARH1 and ARH3, Mac1 did not require Mg 2+ for optimal activity. 36945431 15 79 from insights 1894:1901 arg1 activities 1911:1920 Nsp3 activities 1906:1920 Nsp3 activities 1906:1920 New insights on Nsp3 activities may shed light on potential SARS-CoV-2 therapeutic targets. 36945431 7 80 theme ADP-ribose-acceptor 993:1011 arg1 bond 1013:1016 cleavage ADP-ribose-acceptor bond 984:1016 cleavage ADP-ribose-acceptor bond 984:1016 On the other hand, some viral macrodomains cleavage ADP-ribose-acceptor bond, generating free ADP-ribose. 36945431 2 81 theme several 273:279 arg1 virus 259:263 The virus 255:263 The virus 255:263 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 2 81 theme several 273:279 arg1 Nsps 306:309 Nsps 306:309 Nsps 306:309 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 2 81 theme several 273:279 arg1 proteins 296:303 several non-structural proteins 273:303 several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes 273:373 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 11 82 dep ARH1 1373:1376 arg1 contrast 1361:1368 contrast 1361:1368 contrast 1361:1368 In contrast to ARH1 and ARH3, Mac1 did not require Mg 2+ for optimal activity. 36945431 0 83 theme ADP-ribosylated 74:88 arg1 Substrates 90:99 Diverse ADP-ribosylated Substrates 66:99 Diverse ADP-ribosylated Substrates 66:99 Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 Hydrolyzes Diverse ADP-ribosylated Substrates. 36945431 16 84 theme macrodomain-containing 2051:2072 arg1 proteins 2074:2081 3 macrodomain-containing proteins 2049:2081 3 macrodomain-containing proteins 2049:2081 IMPORTANCE SARS-CoV-2, the virus responsible for COVID-19, encodes 3 macrodomain-containing proteins, e.g., Mac1, Mac2, Mac3, within non-structural proteins 3 (Nsp3). 36945431 16 84 theme macrodomain-containing 2051:2072 arg1 IMPORTANCE 1982:1991 IMPORTANCE SARS-CoV-2 1982:2002 IMPORTANCE SARS-CoV-2 1982:2002 IMPORTANCE SARS-CoV-2, the virus responsible for COVID-19, encodes 3 macrodomain-containing proteins, e.g., Mac1, Mac2, Mac3, within non-structural proteins 3 (Nsp3). 36945431 9 85 from activities 1188:1197 arg1 substrates 1231:1240 substrates 1231:1240 substrates containing ADP-ribose 1231:1262 Here, we examined potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose. 36945431 7 86 theme other 948:952 arg1 hand 954:957 the other hand 944:957 the other hand 944:957 On the other hand, some viral macrodomains cleavage ADP-ribose-acceptor bond, generating free ADP-ribose. 36945431 13 87 theme H3 1615:1616 arg1 peptide 1618:1624 α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide 1559:1624 peptide 1618:1624 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 22 88 theme pathways 2690:2697 arg1 multi-function 2581:2594 multi-function 2581:2594 multi-function 2581:2594 These data suggest that Mac1 may have multi-function as a α-NAD + consumer for viral replication and a disruptor of host-mediated ADP-ribosylation pathways. 36945431 22 88 theme pathways 2690:2697 arg1 disruptor 2646:2654 a disruptor 2644:2654 a disruptor of host-mediated ADP-ribosylation pathways 2644:2697 These data suggest that Mac1 may have multi-function as a α-NAD + consumer for viral replication and a disruptor of host-mediated ADP-ribosylation pathways. 36945431 12 89 theme ADP-ribose-1 1483:1494 arg1 -phosphat 1496:1504 ADP-ribose-1"-phosphat 1483:1504 ADP-ribose-1"-phosphat 1483:1504 Mac1 also hydrolyzed O -acetyl-ADP-ribose and ADP-ribose-1"-phosphat, but not Mac2 and Mac3. 36945431 4 90 from pathways 574:581 arg1 cells 596:600 mammalian cells 586:600 mammalian cells 586:600 Mac1 has been shown to increase SARS-CoV-2 virulence and disrupt ADP-ribosylation pathways in mammalian cells. 36945431 23 91 theme therapeutic 2775:2785 arg1 targets 2787:2793 possible therapeutic targets 2766:2793 possible therapeutic targets for COVID-19 2766:2806 Understanding Mac1's mechanisms of action is important to provide possible therapeutic targets for COVID-19. 36945431 1 92 theme Severe 102:107 arg1 coronavirus 136:146 Severe acute respiratory syndrome coronavirus 2 102:148 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 102:161 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36945431 1 92 theme Severe 102:107 arg1 SARS-CoV-2 151:160 SARS-CoV-2 151:160 SARS-CoV-2 151:160 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36945431 0 93 theme SARS-CoV-2 20:29 arg1 Protein 45:51 SARS-CoV-2 Nonstructural Protein 3 20:53 SARS-CoV-2 Nonstructural Protein 3 20:53 Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 Hydrolyzes Diverse ADP-ribosylated Substrates. 36945431 22 94 dep α-NAD 2601:2605 arg1 a 2599:2599 a 2599:2599 a 2599:2599 These data suggest that Mac1 may have multi-function as a α-NAD + consumer for viral replication and a disruptor of host-mediated ADP-ribosylation pathways. 36945431 1 95 theme respiratory 115:125 arg1 coronavirus 136:146 Severe acute respiratory syndrome coronavirus 2 102:148 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 102:161 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36945431 1 95 theme respiratory 115:125 arg1 SARS-CoV-2 151:160 SARS-CoV-2 151:160 SARS-CoV-2 151:160 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36945431 15 96 theme potential 1940:1948 arg1 targets 1973:1979 potential SARS-CoV-2 therapeutic targets 1940:1979 potential SARS-CoV-2 therapeutic targets 1940:1979 New insights on Nsp3 activities may shed light on potential SARS-CoV-2 therapeutic targets. 36945431 0 97 theme Protein 45:51 arg1 Mac1 12:15 Macrodomain Mac1 0:15 Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 0:53 Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 Hydrolyzes Diverse ADP-ribosylated Substrates. 36945431 6 98 theme toxins 832:837 arg1 action 812:817 action 812:817 action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways 812:938 ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. 36945431 13 99 from site 1751:1754 arg1 moiety 1774:1779 the ADP-ribose moiety 1759:1779 the ADP-ribose moiety 1759:1779 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 13 99 from site 1751:1754 arg1 specificity 1722:1732 specificity 1722:1732 specificity at the catalytic site in the ADP-ribose moiety 1722:1779 However, Mac1 did not cleave α-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. 36945431 23 100 theme action 2735:2740 arg1 mechanisms 2721:2730 Mac1's mechanisms 2714:2730 Mac1's mechanisms of action 2714:2740 Understanding Mac1's mechanisms of action is important to provide possible therapeutic targets for COVID-19. 36945431 8 101 from homeostasis 1122:1132 arg1 cells 1142:1146 host cells 1137:1146 host cells 1137:1146 By this reaction, the macrodomain-containing proteins interfere ADP-ribose homeostasis in host cells. 36945431 3 102 theme host 480:483 arg1 cells 485:489 host cells 480:489 host cells 480:489 Among these Nsp proteins, Nsp3 contains macrodomains, e.g., Mac1, Mac2, Mac3, with potential effects on host cells. 36945431 8 103 theme ADP-ribose 1111:1120 arg1 homeostasis 1122:1132 ADP-ribose homeostasis 1111:1132 ADP-ribose homeostasis in host cells 1111:1146 By this reaction, the macrodomain-containing proteins interfere ADP-ribose homeostasis in host cells. 36945431 14 104 theme host-mediated 1858:1870 arg1 ADP-ribosylation 1872:1887 host-mediated ADP-ribosylation 1858:1887 host-mediated ADP-ribosylation 1858:1887 We conclude that SARS-CoV-2 Mac1 may exert anti-viral activity by reversing host-mediated ADP-ribosylation. 36945431 15 105 theme Nsp3 1906:1909 arg1 activities 1911:1920 Nsp3 activities 1906:1920 Nsp3 activities 1906:1920 New insights on Nsp3 activities may shed light on potential SARS-CoV-2 therapeutic targets. 36945431 2 106 theme capable 334:340 arg1 elements 325:332 elements 325:332 elements capable of disrupting cellular processes 325:373 The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. 36945431 1 107 theme deaths 237:242 arg1 worldwide 244:252 6-million deaths worldwide 227:252 6-million deaths worldwide 227:252 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. 36248868 2 0 from variants 389:396 arg1 gene 410:413 the ADA2 gene 401:413 the ADA2 gene 401:413 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 10 1 theme important 2024:2032 arg1 secretion 1990:1998 The impaired secretion 1977:1998 The impaired secretion of L351Q ADA2 1977:2012 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 10 1 theme important 2024:2032 arg1 factor 2034:2039 an important factor 2021:2039 an important factor leading to the severe phenotype observed in patients with this variant 2021:2110 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 8 2 theme asparagine 1801:1810 arg1 residues 1812:1819 neighboring asparagine residues 1789:1819 neighboring asparagine residues 1789:1819 Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. 36248868 6 3 theme Interferon 1404:1413 arg1 IRF7 1450:1453 IRF7 1450:1453 IRF7 1450:1453 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 3 theme Interferon 1404:1413 arg1 ISGs 1433:1436 ISGs 1433:1436 ISGs 1433:1436 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 3 theme Interferon 1404:1413 arg1 IFIT3 1440:1444 IFIT3 1440:1444 IFIT3 1440:1444 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 3 theme Interferon 1404:1413 arg1 genes 1426:1430 Type I Interferon stimulated genes 1397:1430 Type I Interferon stimulated genes (ISGs) 1397:1437 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 10 4 located observed 2073:2080 arg2 phenotype 2063:2071 the severe phenotype 2052:2071 the severe phenotype observed in patients with this variant 2052:2110 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 10 4 located observed 2073:2080 arg1 patients 2085:2092 patients 2085:2092 patients with this variant 2085:2110 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 2 5 theme manifestations 551:564 arg1 defects 602:608 hematological defects 588:608 hematological defects 588:608 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 5 theme manifestations 551:564 arg1 cytopenia 614:622 cytopenia 614:622 cytopenia 614:622 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 5 theme manifestations 551:564 arg1 vasculitis 576:585 vasculitis 576:585 vasculitis 576:585 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 5 theme manifestations 551:564 arg1 range 529:533 an unusually broad range 510:533 an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia 510:622 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 3 6 from located 814:820 arg1 domain 839:844 the catalytic domain 825:844 the catalytic domain of the protein 825:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 3 6 from located 814:820 arg1 protein 853:859 the protein 849:859 the protein 849:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 4 7 theme pathogenic 989:998 arg1 variant 1006:1012 the pathogenic L351Q variant 985:1012 the pathogenic L351Q variant identified in DADA2 patients 985:1041 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 3 8 theme ADA2 681:684 arg1 variants 686:693 ADA2 variants 681:693 ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein 681:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 9 9 dep ISGs 1900:1903 arg1 ISGs 1900:1903 Type I ISGs IFIT3 and IRF7 1893:1918 Type I ISGs IFIT3 and IRF7 1893:1918 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 9 9 dep ISGs 1900:1903 arg1 IRF7 1915:1918 IRF7 1915:1918 IRF7 1915:1918 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 9 9 dep ISGs 1900:1903 arg1 IFIT3 1905:1909 IFIT3 1905:1909 IFIT3 1905:1909 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 4 10 dep Methods 862:868 arg1 cells 893:897 Mammalian (Flp-IN CHO) cells 870:897 Methods Mammalian (Flp-IN CHO) cells 862:897 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 2 11 theme hematological 588:600 arg1 defects 602:608 hematological defects 588:608 hematological defects 588:608 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 10 12 theme L351Q 2003:2007 arg1 ADA2 2009:2012 L351Q ADA2 2003:2012 L351Q ADA2 2003:2012 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 9 13 theme Constitutive 1866:1877 arg1 expression 1879:1888 Constitutive expression 1866:1888 Constitutive expression of Type I ISGs IFIT3 and IRF7 1866:1918 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 7 14 theme intracellular 1577:1589 arg1 accumulation 1591:1602 an intracellular accumulation 1574:1602 an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants 1574:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 7 15 theme protein 1697:1703 arg1 variants 1705:1712 wild-type ADA2 or other ADA2 protein variants 1668:1712 variants 1705:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 3 16 theme association 704:714 arg1 variants 686:693 ADA2 variants 681:693 ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein 681:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 0 17 theme IFN 106:108 arg1 expression 126:135 type I IFN responsive gene expression 99:135 type I IFN responsive gene expression 99:135 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 10 18 dep Conclusions 1965:1975 arg1 secretion 1990:1998 The impaired secretion 1977:1998 The impaired secretion of L351Q ADA2 1977:2012 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 10 18 dep Conclusions 1965:1975 arg1 factor 2034:2039 an important factor 2021:2039 an important factor leading to the severe phenotype observed in patients with this variant 2021:2110 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 9 19 theme I 1898:1898 arg1 ISGs 1900:1903 Type I ISGs IFIT3 and IRF7 1893:1918 Type I ISGs IFIT3 and IRF7 1893:1918 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 9 19 theme I 1898:1898 arg1 IRF7 1915:1918 IRF7 1915:1918 IRF7 1915:1918 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 9 19 theme I 1898:1898 arg1 IFIT3 1905:1909 IFIT3 1905:1909 IFIT3 1905:1909 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 0 20 theme gene 121:124 arg1 expression 126:135 type I IFN responsive gene expression 99:135 type I IFN responsive gene expression 99:135 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 7 21 theme ADA2 1556:1559 arg1 secretion 1537:1545 secretion 1537:1545 secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants 1537:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 7 22 dep abrogating 1479:1488 arg1 addition 1467:1474 addition 1467:1474 addition 1467:1474 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 2 23 theme broad 523:527 arg1 defects 602:608 hematological defects 588:608 hematological defects 588:608 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 23 theme broad 523:527 arg1 cytopenia 614:622 cytopenia 614:622 cytopenia 614:622 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 23 theme broad 523:527 arg1 vasculitis 576:585 vasculitis 576:585 vasculitis 576:585 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 23 theme broad 523:527 arg1 range 529:533 an unusually broad range 510:533 an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia 510:622 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 3 24 from domain 839:844 arg1 located 814:820 located 814:820 located 814:820 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 3 25 dep referred 784:791 arg1 herein 777:782 herein 777:782 herein 777:782 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 7 26 theme wild-type 1668:1676 arg1 ADA2 1678:1681 wild-type ADA2 or other ADA2 protein variants 1668:1712 ADA2 1678:1681 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 3 27 theme unique 746:751 arg1 c.1052T>A 753:761 a unique c.1052T>A 744:761 a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein 744:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 8 28 theme ADA2 1734:1737 arg1 Retention 1715:1723 Retention 1715:1723 Retention of L351Q ADA2 1715:1737 Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. 36248868 1 29 theme Background 138:147 arg1 ADA2 172:175 ADA2 172:175 ADA2 172:175 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 1 29 theme Background 138:147 arg1 enzyme 210:215 a homodimeric, extracellular enzyme 181:215 enzyme 210:215 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 1 29 theme Background 138:147 arg1 deaminase 159:167 Background Adenosine deaminase 2 138:169 Background Adenosine deaminase 2 (ADA2) 138:176 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 7 30 theme L351Q 1514:1518 arg1 variant 1520:1526 the L351Q variant 1510:1526 the L351Q variant 1510:1526 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 0 31 from c.1052T>A 19:27 arg1 deaminase 56:64 adenosine deaminase 2 46:66 adenosine deaminase 2 46:66 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 8 32 from glycosylation 1772:1784 arg1 residues 1812:1819 neighboring asparagine residues 1789:1819 neighboring asparagine residues 1789:1819 Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. 36248868 5 33 theme inhibition 1194:1203 arg1 outcome 1160:1166 the outcome 1156:1166 the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) 1156:1270 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 2 34 theme inflammatory 538:549 arg1 cytopenia 614:622 cytopenia 614:622 cytopenia 614:622 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 34 theme inflammatory 538:549 arg1 vasculitis 576:585 vasculitis 576:585 vasculitis 576:585 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 34 theme inflammatory 538:549 arg1 defects 602:608 hematological defects 588:608 hematological defects 588:608 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 34 theme inflammatory 538:549 arg1 manifestations 551:564 inflammatory manifestations 538:564 inflammatory manifestations including vasculitis, hematological defects and cytopenia 538:622 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 3 35 theme located 814:820 arg1 variant 806:812 a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant 744:812 a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein 744:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 2 36 theme recessive 476:484 arg1 disease 486:492 an autosomal recessive disease 463:492 an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia 463:622 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 36 theme recessive 476:484 arg1 ADA2 449:452 ADA2 449:452 ADA2 (DADA2) 449:460 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 5 37 link N-linked 1248:1255 arg1 glycosylation 1257:1269 N-linked glycosylation 1248:1269 N-linked glycosylation 1248:1269 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 9 38 theme L351Q 1953:1957 arg1 ADA2 1959:1962 L351Q ADA2 1953:1962 L351Q ADA2 1953:1962 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 5 39 theme protein 1208:1214 arg1 processing 1216:1225 protein processing 1208:1225 protein processing (Golgi transport and N-linked glycosylation) 1208:1270 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 6 40 theme real-time 1321:1329 arg1 RT-qPCR 1336:1342 RT-qPCR 1336:1342 RT-qPCR 1336:1342 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 40 theme real-time 1321:1329 arg1 PCR 1331:1333 Reverse transcription quantitative real-time PCR 1286:1333 Reverse transcription quantitative real-time PCR (RT-qPCR) 1286:1343 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 1 41 theme extracellular 324:336 arg1 adenosine 338:346 extracellular adenosine 324:346 extracellular adenosine to inosine 324:357 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 7 42 theme catalytic 1490:1498 arg1 activity 1500:1507 catalytic activity 1490:1507 catalytic activity 1490:1507 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 2 43 theme catalytic 369:377 arg1 variants 389:396 Loss-of-(catalytic)-function variants 360:396 Loss-of-(catalytic)-function variants in the ADA2 gene 360:413 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 0 44 theme type 99:102 arg1 IFN 106:108 type I IFN 99:108 type I IFN responsive gene expression 99:135 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 3 45 with association 704:714 arg1 DADA2 721:725 DADA2 721:725 DADA2 721:725 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 7 46 theme protein 1618:1624 arg1 accumulation 1591:1602 an intracellular accumulation 1574:1602 an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants 1574:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 4 47 theme protein 957:963 arg1 variants 965:972 wild-type ADA2 and ADA2 protein variants 933:972 wild-type ADA2 and ADA2 protein variants 933:972 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 4 47 theme protein 957:963 arg1 variant 1006:1012 the pathogenic L351Q variant 985:1012 the pathogenic L351Q variant identified in DADA2 patients 985:1041 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 2 48 theme Loss-of- 360:367 arg1 variants 389:396 Loss-of-(catalytic)-function variants 360:396 Loss-of-(catalytic)-function variants in the ADA2 gene 360:413 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 0 49 theme Pathogenic 0:9 arg1 c.1052T>A 19:27 Pathogenic variant c.1052T>A 0:27 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 0:66 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 0 49 theme Pathogenic 0:9 arg1 p.Leu351Gln 30:40 p.Leu351Gln 30:40 p.Leu351Gln 30:40 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 5 50 theme catalytic 1104:1112 arg1 activity 1114:1121 ADA2 catalytic activity 1099:1121 ADA2 catalytic activity 1099:1121 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 8 51 theme neighboring 1789:1799 arg1 residues 1812:1819 neighboring asparagine residues 1789:1819 neighboring asparagine residues 1789:1819 Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. 36248868 7 52 theme L351Q 1607:1611 arg1 protein 1618:1624 L351Q ADA2 protein 1607:1624 L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants 1607:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 2 53 theme ADA2 405:408 arg1 gene 410:413 the ADA2 gene 401:413 the ADA2 gene 401:413 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 5 54 theme N-linked 1248:1255 arg1 glycosylation 1257:1269 N-linked glycosylation 1248:1269 N-linked glycosylation 1248:1269 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 6 55 theme relative 1374:1381 arg1 expression 1383:1392 the relative expression 1370:1392 the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7 1370:1453 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 4 56 theme wild-type 933:941 arg1 variants 965:972 wild-type ADA2 and ADA2 protein variants 933:972 wild-type ADA2 and ADA2 protein variants 933:972 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 4 56 theme wild-type 933:941 arg1 variant 1006:1012 the pathogenic L351Q variant 985:1012 the pathogenic L351Q variant identified in DADA2 patients 985:1041 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 2 57 theme -function 379:387 arg1 variants 389:396 Loss-of-(catalytic)-function variants 360:396 Loss-of-(catalytic)-function variants in the ADA2 gene 360:413 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 9 58 located observed 1924:1931 arg2 expression 1879:1888 Constitutive expression 1866:1888 Constitutive expression of Type I ISGs IFIT3 and IRF7 1866:1918 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 9 58 located observed 1924:1931 arg1 cells 1936:1940 cells 1936:1940 cells expressing L351Q ADA2 1936:1962 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 5 59 used used 1084:1087 arg2 immunoblotting 1064:1077 immunoblotting 1064:1077 immunoblotting 1064:1077 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 5 59 used used 1084:1087 arg2 assay 1054:1058 An enzyme assay 1044:1058 An enzyme assay 1044:1058 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 1 60 theme lineage 285:291 arg1 cells 264:268 cells 264:268 cells of the myeloid lineage 264:291 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 1 61 theme extracellular 196:208 arg1 enzyme 210:215 a homodimeric, extracellular enzyme 181:215 enzyme 210:215 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 1 61 theme extracellular 196:208 arg1 deaminase 159:167 Background Adenosine deaminase 2 138:169 Background Adenosine deaminase 2 (ADA2) 138:176 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 4 62 theme DADA2 1028:1032 arg1 patients 1034:1041 DADA2 patients 1028:1041 DADA2 patients 1028:1041 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 3 63 theme c.1052T>A 753:761 arg1 variant 806:812 a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant 744:812 a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein 744:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 6 64 theme stimulated 1415:1424 arg1 IRF7 1450:1453 IRF7 1450:1453 IRF7 1450:1453 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 64 theme stimulated 1415:1424 arg1 ISGs 1433:1436 ISGs 1433:1436 ISGs 1433:1436 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 64 theme stimulated 1415:1424 arg1 IFIT3 1440:1444 IFIT3 1440:1444 IFIT3 1440:1444 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 64 theme stimulated 1415:1424 arg1 genes 1426:1430 Type I Interferon stimulated genes 1397:1430 Type I Interferon stimulated genes (ISGs) 1397:1437 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 1 65 theme growth 230:235 arg1 factor 237:242 putative growth factor 221:242 putative growth factor 221:242 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 4 66 theme L351Q 1000:1004 arg1 variant 1006:1012 the pathogenic L351Q variant 985:1012 the pathogenic L351Q variant identified in DADA2 patients 985:1041 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 7 67 located observed 1639:1646 arg1 cells 1651:1655 cells 1651:1655 cells expressing wild-type ADA2 or other ADA2 protein variants 1651:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 7 67 located observed 1639:1646 arg2 protein 1618:1624 L351Q ADA2 protein 1607:1624 L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants 1607:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 5 68 dep processing 1216:1225 arg1 glycosylation 1257:1269 N-linked glycosylation 1248:1269 N-linked glycosylation 1248:1269 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 5 68 dep processing 1216:1225 arg1 transport 1234:1242 Golgi transport 1228:1242 Golgi transport 1228:1242 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 10 69 theme severe 2056:2061 arg1 phenotype 2063:2071 the severe phenotype 2052:2071 the severe phenotype observed in patients with this variant 2052:2110 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 3 70 theme novel 698:702 arg1 association 704:714 novel association 698:714 novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein 698:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 3 71 theme variants 686:693 arg1 identification 663:676 the identification 659:676 the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein 659:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 10 72 with patients 2085:2092 arg1 variant 2104:2110 this variant 2099:2110 this variant 2099:2110 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 7 73 theme ADA2 1692:1695 arg1 variants 1705:1712 wild-type ADA2 or other ADA2 protein variants 1668:1712 variants 1705:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 6 74 theme Reverse 1286:1292 arg1 RT-qPCR 1336:1342 RT-qPCR 1336:1342 RT-qPCR 1336:1342 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 74 theme Reverse 1286:1292 arg1 PCR 1331:1333 Reverse transcription quantitative real-time PCR 1286:1333 Reverse transcription quantitative real-time PCR (RT-qPCR) 1286:1343 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 9 75 theme Type 1893:1896 arg1 ISGs 1900:1903 Type I ISGs IFIT3 and IRF7 1893:1918 Type I ISGs IFIT3 and IRF7 1893:1918 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 9 75 theme Type 1893:1896 arg1 IRF7 1915:1918 IRF7 1915:1918 IRF7 1915:1918 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 9 75 theme Type 1893:1896 arg1 IFIT3 1905:1909 IFIT3 1905:1909 IFIT3 1905:1909 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 3 76 dep c.1052T>A 753:761 arg1 referred 784:791 referred 784:791 referred to as L351Q 784:803 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 1 77 theme homodimeric 183:193 arg1 enzyme 210:215 a homodimeric, extracellular enzyme 181:215 enzyme 210:215 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 1 77 theme homodimeric 183:193 arg1 deaminase 159:167 Background Adenosine deaminase 2 138:169 Background Adenosine deaminase 2 (ADA2) 138:176 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 7 78 theme L351Q 1550:1554 arg1 ADA2 1556:1559 L351Q ADA2 1550:1559 L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants 1550:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 4 79 theme Mammalian 870:878 arg1 cells 893:897 Mammalian (Flp-IN CHO) cells 870:897 Methods Mammalian (Flp-IN CHO) cells 862:897 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 9 80 theme ISGs 1900:1903 arg1 expression 1879:1888 Constitutive expression 1866:1888 Constitutive expression of Type I ISGs IFIT3 and IRF7 1866:1918 Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. 36248868 4 81 theme CHO 888:890 arg1 cells 893:897 Mammalian (Flp-IN CHO) cells 870:897 Methods Mammalian (Flp-IN CHO) cells 862:897 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 0 82 theme responsive 110:119 arg1 expression 126:135 type I IFN responsive gene expression 99:135 type I IFN responsive gene expression 99:135 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 5 83 theme processing 1216:1225 arg1 inhibition 1194:1203 experimentally induced inhibition 1171:1203 experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) 1171:1270 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 7 84 theme other 1686:1690 arg1 variants 1705:1712 wild-type ADA2 or other ADA2 protein variants 1668:1712 variants 1705:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 5 85 theme Golgi 1228:1232 arg1 transport 1234:1242 Golgi transport 1228:1242 Golgi transport 1228:1242 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 8 86 dep cell 1840:1843 arg1 integrity 1855:1863 integrity 1855:1863 integrity 1855:1863 Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. 36248868 8 86 dep cell 1840:1843 arg1 growth 1845:1850 growth 1845:1850 growth 1845:1850 Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. 36248868 5 87 theme induced 1186:1192 arg1 inhibition 1194:1203 experimentally induced inhibition 1171:1203 experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) 1171:1270 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 4 88 theme Flp-IN 881:886 arg1 cells 893:897 Mammalian (Flp-IN CHO) cells 870:897 Methods Mammalian (Flp-IN CHO) cells 862:897 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 8 89 theme L351Q 1728:1732 arg1 ADA2 1734:1737 L351Q ADA2 1728:1737 L351Q ADA2 1728:1737 Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. 36248868 1 90 theme Adenosine 149:157 arg1 ADA2 172:175 ADA2 172:175 ADA2 172:175 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 1 90 theme Adenosine 149:157 arg1 enzyme 210:215 a homodimeric, extracellular enzyme 181:215 enzyme 210:215 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 1 90 theme Adenosine 149:157 arg1 deaminase 159:167 Background Adenosine deaminase 2 138:169 Background Adenosine deaminase 2 (ADA2) 138:176 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 3 91 theme catalytic 829:837 arg1 domain 839:844 the catalytic domain 825:844 the catalytic domain of the protein 825:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 3 91 theme catalytic 829:837 arg1 protein 853:859 the protein 849:859 the protein 849:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 2 92 theme ADA2 449:452 arg1 Deficiency 435:444 Deficiency 435:444 Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia 435:622 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 1 93 dep produced 252:259 arg1 deaminates 313:322 deaminates 313:322 deaminates extracellular adenosine to inosine 313:357 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 10 94 theme catalytic 2175:2183 arg1 activity 2185:2192 catalytic activity 2175:2192 catalytic activity 2175:2192 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 10 95 theme impaired 1981:1988 arg1 factor 2034:2039 an important factor 2021:2039 an important factor leading to the severe phenotype observed in patients with this variant 2021:2110 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 10 95 theme impaired 1981:1988 arg1 secretion 1990:1998 The impaired secretion 1977:1998 The impaired secretion of L351Q ADA2 1977:2012 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 2 96 theme autosomal 466:474 arg1 disease 486:492 an autosomal recessive disease 463:492 an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia 463:622 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 2 96 theme autosomal 466:474 arg1 ADA2 449:452 ADA2 449:452 ADA2 (DADA2) 449:460 Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. 36248868 6 97 theme quantitative 1308:1319 arg1 RT-qPCR 1336:1342 RT-qPCR 1336:1342 RT-qPCR 1336:1342 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 97 theme quantitative 1308:1319 arg1 PCR 1331:1333 Reverse transcription quantitative real-time PCR 1286:1333 Reverse transcription quantitative real-time PCR (RT-qPCR) 1286:1343 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 3 98 dep variant 806:812 arg1 DADA2 721:725 DADA2 721:725 DADA2 721:725 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 3 98 dep variant 806:812 arg1 was 740:742 was 740:742 was 740:742 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 3 99 theme protein 853:859 arg1 domain 839:844 the catalytic domain 825:844 the catalytic domain of the protein 825:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 3 99 theme protein 853:859 arg1 protein 853:859 the protein 849:859 the protein 849:859 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 10 100 theme genotype-phenotype 2210:2227 arg1 relationships 2229:2241 genotype-phenotype relationships 2210:2241 genotype-phenotype relationships 2210:2241 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 0 101 theme I 104:104 arg1 IFN 106:108 type I IFN 99:108 type I IFN responsive gene expression 99:135 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 0 102 theme variant 11:17 arg1 c.1052T>A 19:27 Pathogenic variant c.1052T>A 0:27 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 0:66 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 0 102 theme variant 11:17 arg1 p.Leu351Gln 30:40 p.Leu351Gln 30:40 p.Leu351Gln 30:40 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 5 103 theme enzyme 1047:1052 arg1 assay 1054:1058 An enzyme assay 1044:1058 An enzyme assay 1044:1058 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 8 104 theme impaired 1763:1770 arg1 glycosylation 1772:1784 impaired glycosylation 1763:1784 impaired glycosylation on neighboring asparagine residues 1763:1819 Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. 36248868 4 105 theme ADA2 952:955 arg1 variants 965:972 wild-type ADA2 and ADA2 protein variants 933:972 wild-type ADA2 and ADA2 protein variants 933:972 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 4 105 theme ADA2 952:955 arg1 variant 1006:1012 the pathogenic L351Q variant 985:1012 the pathogenic L351Q variant identified in DADA2 patients 985:1041 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 7 106 theme ADA2 1613:1616 arg1 protein 1618:1624 L351Q ADA2 protein 1607:1624 L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants 1607:1712 Results In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. 36248868 3 107 theme Previous 625:632 arg1 work 634:637 Previous work 625:637 Previous work by our group 625:650 Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. 36248868 8 108 gly glycosylation 1772:1784 arg1 residues 1812:1819 neighboring asparagine residues 1789:1819 neighboring asparagine residues 1789:1819 Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. 36248868 6 109 theme transcription 1294:1306 arg1 RT-qPCR 1336:1342 RT-qPCR 1336:1342 RT-qPCR 1336:1342 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 109 theme transcription 1294:1306 arg1 PCR 1331:1333 Reverse transcription quantitative real-time PCR 1286:1333 Reverse transcription quantitative real-time PCR (RT-qPCR) 1286:1343 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 0 110 theme adenosine 46:54 arg1 deaminase 56:64 adenosine deaminase 2 46:66 adenosine deaminase 2 46:66 Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression. 36248868 1 111 theme myeloid 277:283 arg1 lineage 285:291 the myeloid lineage 273:291 the myeloid lineage 273:291 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 36248868 4 112 theme ADA2 943:946 arg1 variants 965:972 wild-type ADA2 and ADA2 protein variants 933:972 wild-type ADA2 and ADA2 protein variants 933:972 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 4 112 theme ADA2 943:946 arg1 variant 1006:1012 the pathogenic L351Q variant 985:1012 the pathogenic L351Q variant identified in DADA2 patients 985:1041 Methods Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. 36248868 5 113 theme ADA2 1099:1102 arg1 activity 1114:1121 ADA2 catalytic activity 1099:1121 ADA2 catalytic activity 1099:1121 An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. 36248868 10 114 theme ADA2 2009:2012 arg1 factor 2034:2039 an important factor 2021:2039 an important factor leading to the severe phenotype observed in patients with this variant 2021:2110 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 10 114 theme ADA2 2009:2012 arg1 secretion 1990:1998 The impaired secretion 1977:1998 The impaired secretion of L351Q ADA2 1977:2012 Conclusions The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2. 36248868 6 115 theme Type 1397:1400 arg1 Interferon 1404:1413 Type I Interferon 1397:1413 Type I Interferon stimulated genes (ISGs) 1397:1437 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 6 116 theme genes 1426:1430 arg1 expression 1383:1392 the relative expression 1370:1392 the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7 1370:1453 Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. 36248868 1 117 theme putative 221:228 arg1 factor 237:242 putative growth factor 221:242 putative growth factor 221:242 Background Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. 35313591 9 0 theme targets 1376:1382 arg1 catalog 1343:1349 a catalog 1341:1349 a catalog of potential therapeutic targets 1341:1382 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35313591 5 1 theme SARS-CoV-2 673:682 arg1 proteins 684:691 SARS-CoV-2 proteins 673:691 SARS-CoV-2 proteins expressed in human lung epithelial cells 673:732 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35313591 4 2 theme separate 606:613 arg1 roles 615:619 their shared and separate roles 589:619 their shared and separate roles in replication, transcription, and viral packaging 589:670 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 3 3 theme SARS-CoV-2 349:358 arg1 interactions 368:379 SARS-CoV-2 protein interactions 349:379 SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells 349:438 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35313591 4 4 theme RNA 548:550 arg1 genome 558:563 the RNA viral genome 544:563 the RNA viral genome 544:563 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 7 5 theme different 1134:1142 arg1 variants 1155:1162 different SARS-CoV-2 variants 1134:1162 different SARS-CoV-2 variants 1134:1162 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 7 6 theme host 1114:1117 arg1 targets 1119:1125 potential antiviral host targets 1094:1125 potential antiviral host targets across different SARS-CoV-2 variants 1094:1162 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 9 7 theme viral 1302:1306 arg1 interactome 1320:1330 Our viral protein-RNA interactome 1298:1330 Our viral protein-RNA interactome 1298:1330 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35313591 5 8 theme host 754:757 arg1 RNAs 766:769 4773 unique host coding RNAs 742:769 4773 unique host coding RNAs 742:769 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35313591 6 9 theme ER 943:944 arg1 processing 946:955 ER processing 943:955 ER processing 943:955 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 7 10 theme host 1018:1021 arg1 genes 1023:1027 host genes 1018:1027 host genes targeted by viral proteins in human lung organoid cells 1018:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 3 11 theme host 396:399 arg1 RNAs 401:404 viral and host RNAs 386:404 viral and host RNAs 386:404 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35313591 9 12 dep a 1436:1436 arg1 safeguard 1438:1446 safeguard 1438:1446 safeguard against future pandemics 1438:1471 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35313591 4 13 from regions 533:539 arg1 genome 558:563 the RNA viral genome 544:563 the RNA viral genome 544:563 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 7 14 theme siRNA 999:1003 arg1 knockdown 1005:1013 siRNA knockdown 999:1013 siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells 999:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 8 15 theme cytokine 1248:1255 arg1 productions 1257:1267 cytokine productions 1248:1267 cytokine productions 1248:1267 Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. 35313591 8 15 theme cytokine 1248:1255 arg1 interleukin-1α/β 1280:1295 interleukin-1α/β 1280:1295 interleukin-1α/β 1280:1295 Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. 35313591 4 16 theme distinct 500:507 arg1 preferences 509:519 distinct preferences 500:519 distinct preferences 500:519 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 4 17 theme SARS-CoV-2 441:450 arg1 NSP12 468:472 NSP12 468:472 NSP12 468:472 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 4 17 theme SARS-CoV-2 441:450 arg1 nucleocapsid 479:490 nucleocapsid 479:490 nucleocapsid 479:490 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 4 17 theme SARS-CoV-2 441:450 arg1 NSP8 462:465 NSP8 462:465 NSP8 462:465 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 4 17 theme SARS-CoV-2 441:450 arg1 proteins 452:459 SARS-CoV-2 proteins 441:459 SARS-CoV-2 proteins 441:459 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 1 18 theme COVID-19 83:90 arg1 pandemic 92:99 The COVID-19 pandemic 79:99 The COVID-19 pandemic 79:99 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35313591 3 19 theme viral 386:390 arg1 RNAs 401:404 viral and host RNAs 386:404 viral and host RNAs 386:404 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35313591 4 20 theme specific 524:531 arg1 regions 533:539 specific regions 524:539 specific regions in the RNA viral genome 524:563 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 9 21 theme potential 1354:1362 arg1 targets 1376:1382 potential therapeutic targets 1354:1382 potential therapeutic targets 1354:1382 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35313591 2 22 contain has 195:197 arg1 betacoronvirus 180:193 The betacoronvirus 176:193 The betacoronvirus 176:193 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35313591 2 22 contain has 195:197 arg2 genome 220:225 a positive sense RNA genome 199:225 a positive sense RNA genome which encodes for several RNA binding proteins 199:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35313591 3 23 theme authentic 409:417 arg1 cells 434:438 authentic virus-infected cells 409:438 authentic virus-infected cells 409:438 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35313591 7 24 from proteins 1047:1054 arg1 cells 1079:1083 human lung organoid cells 1059:1083 human lung organoid cells 1059:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 7 25 theme potential 1094:1102 arg1 targets 1119:1125 potential antiviral host targets 1094:1125 potential antiviral host targets across different SARS-CoV-2 variants 1094:1162 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 8 26 theme gene 1196:1199 arg1 expression 1201:1210 host gene expression 1191:1210 host gene expression 1191:1210 Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. 35313591 6 27 theme N-linked 920:927 arg1 glycosylation 929:941 protein N-linked glycosylation ER processing and mitochondrial processes 912:983 glycosylation 929:941 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 3 28 theme virus-infected 419:432 arg1 cells 434:438 authentic virus-infected cells 409:438 authentic virus-infected cells 409:438 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35313591 3 29 from interactions 368:379 arg1 cells 434:438 authentic virus-infected cells 409:438 authentic virus-infected cells 409:438 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35313591 6 30 theme gene 815:818 arg1 expression 820:829 target gene expression 808:829 target gene expression 808:829 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 6 31 from pathways 900:907 arg1 processes 975:983 mitochondrial processes 961:983 mitochondrial processes 961:983 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 6 31 from pathways 900:907 arg1 glycosylation 929:941 protein N-linked glycosylation ER processing and mitochondrial processes 912:983 glycosylation 929:941 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 9 32 theme COVID-19 1424:1431 arg1 etiology 1412:1419 the etiology 1408:1419 the etiology of COVID-19 1408:1431 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35313591 6 33 theme target 808:813 arg1 expression 820:829 target gene expression 808:829 target gene expression 808:829 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 4 34 theme viral 656:660 arg1 packaging 662:670 viral packaging 656:670 viral packaging 656:670 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 0 35 theme functional 14:23 arg1 interrogation 25:37 functional interrogation 14:37 functional interrogation 14:37 Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. 35313591 4 36 theme shared 595:600 arg1 roles 615:619 their shared and separate roles 589:619 their shared and separate roles in replication, transcription, and viral packaging 589:670 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 3 37 theme enhanced 288:295 arg1 crosslinking 297:308 crosslinking 297:308 crosslinking 297:308 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35313591 2 38 theme positive 201:208 arg1 genome 220:225 a positive sense RNA genome 199:225 a positive sense RNA genome which encodes for several RNA binding proteins 199:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35313591 1 39 theme severe 114:119 arg1 syndrome-coronavirus-2 139:160 severe acute respiratory syndrome-coronavirus-2 114:160 severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) 114:173 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35313591 1 39 theme severe 114:119 arg1 SARS-CoV-2 163:172 SARS-CoV-2 163:172 SARS-CoV-2 163:172 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35313591 9 40 theme therapeutic 1364:1374 arg1 targets 1376:1382 potential therapeutic targets 1354:1382 potential therapeutic targets 1354:1382 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35313591 0 41 theme SARS-CoV-2 42:51 arg1 interactions 65:76 SARS-CoV-2 protein-RNA interactions 42:76 SARS-CoV-2 protein-RNA interactions 42:76 Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. 35313591 7 42 theme antiviral 1104:1112 arg1 targets 1119:1125 potential antiviral host targets 1094:1125 potential antiviral host targets across different SARS-CoV-2 variants 1094:1162 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 9 43 theme protein-RNA 1308:1318 arg1 interactome 1320:1330 Our viral protein-RNA interactome 1298:1330 Our viral protein-RNA interactome 1298:1330 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35313591 2 44 theme RNA 253:255 arg1 proteins 265:272 several RNA binding proteins 245:272 several RNA binding proteins 245:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35313591 5 45 theme unique 747:752 arg1 RNAs 766:769 4773 unique host coding RNAs 742:769 4773 unique host coding RNAs 742:769 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35313591 5 46 theme coding 759:764 arg1 RNAs 766:769 4773 unique host coding RNAs 742:769 4773 unique host coding RNAs 742:769 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35313591 2 47 theme several 245:251 arg1 proteins 265:272 several RNA binding proteins 245:272 several RNA binding proteins 245:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35313591 7 48 theme human 1059:1063 arg1 cells 1079:1083 human lung organoid cells 1059:1083 human lung organoid cells 1059:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 6 49 link N-linked 920:927 arg1 glycosylation 929:941 protein N-linked glycosylation ER processing and mitochondrial processes 912:983 glycosylation 929:941 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 0 50 theme interactions 65:76 arg1 Discovery 0:8 Discovery 0:8 Discovery 0:8 Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. 35313591 0 50 theme interactions 65:76 arg1 interrogation 25:37 functional interrogation 14:37 functional interrogation 14:37 Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. 35313591 4 51 theme viral 552:556 arg1 genome 558:563 the RNA viral genome 544:563 the RNA viral genome 544:563 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 5 52 theme human 706:710 arg1 cells 728:732 human lung epithelial cells 706:732 human lung epithelial cells 706:732 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35313591 6 53 theme protein 912:918 arg1 glycosylation 929:941 protein N-linked glycosylation ER processing and mitochondrial processes 912:983 glycosylation 929:941 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 1 54 theme acute 121:125 arg1 syndrome-coronavirus-2 139:160 severe acute respiratory syndrome-coronavirus-2 114:160 severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) 114:173 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35313591 1 54 theme acute 121:125 arg1 SARS-CoV-2 163:172 SARS-CoV-2 163:172 SARS-CoV-2 163:172 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35313591 0 55 theme protein-RNA 53:63 arg1 interactions 65:76 SARS-CoV-2 protein-RNA interactions 42:76 SARS-CoV-2 protein-RNA interactions 42:76 Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. 35313591 9 56 theme future 1456:1461 arg1 pandemics 1463:1471 future pandemics 1456:1471 future pandemics 1456:1471 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35313591 5 57 theme lung 712:715 arg1 cells 728:732 human lung epithelial cells 706:732 human lung epithelial cells 706:732 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35313591 6 58 theme SARS-CoV-2 777:786 arg1 proteins 788:795 Nine SARS-CoV-2 proteins 772:795 Nine SARS-CoV-2 proteins 772:795 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 1 59 theme respiratory 127:137 arg1 syndrome-coronavirus-2 139:160 severe acute respiratory syndrome-coronavirus-2 114:160 severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) 114:173 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35313591 1 59 theme respiratory 127:137 arg1 SARS-CoV-2 163:172 SARS-CoV-2 163:172 SARS-CoV-2 163:172 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35313591 3 60 with interactions 368:379 arg1 RNAs 401:404 viral and host RNAs 386:404 viral and host RNAs 386:404 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35313591 5 61 theme epithelial 717:726 arg1 cells 728:732 human lung epithelial cells 706:732 human lung epithelial cells 706:732 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35313591 6 62 theme RNA 865:867 arg1 substrates 869:878 RNA substrates 865:878 RNA substrates 865:878 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 8 63 theme mRNA 1224:1227 arg1 export 1229:1234 mRNA export 1224:1234 mRNA export 1224:1234 Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. 35313591 2 64 theme RNA 216:218 arg1 genome 220:225 a positive sense RNA genome 199:225 a positive sense RNA genome which encodes for several RNA binding proteins 199:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35313591 7 65 theme lung 1065:1068 arg1 cells 1079:1083 human lung organoid cells 1059:1083 human lung organoid cells 1059:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 7 66 theme SARS-CoV-2 1144:1153 arg1 variants 1155:1162 different SARS-CoV-2 variants 1134:1162 different SARS-CoV-2 variants 1134:1162 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 3 67 theme protein 360:366 arg1 interactions 368:379 SARS-CoV-2 protein interactions 349:379 SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells 349:438 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35313591 2 68 theme sense 210:214 arg1 genome 220:225 a positive sense RNA genome 199:225 a positive sense RNA genome which encodes for several RNA binding proteins 199:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35313591 7 69 theme viral 1041:1045 arg1 proteins 1047:1054 viral proteins 1041:1054 viral proteins in human lung organoid cells 1041:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 6 70 dep glycosylation 929:941 arg1 processing 946:955 ER processing 943:955 ER processing 943:955 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 8 71 theme host 1191:1194 arg1 expression 1201:1210 host gene expression 1191:1210 host gene expression 1191:1210 Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. 35313591 6 72 theme mitochondrial 961:973 arg1 processes 975:983 mitochondrial processes 961:983 mitochondrial processes 961:983 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35313591 2 73 theme binding 257:263 arg1 proteins 265:272 several RNA binding proteins 245:272 several RNA binding proteins 245:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35313591 7 74 theme genes 1023:1027 arg1 knockdown 1005:1013 siRNA knockdown 999:1013 siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells 999:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 7 75 theme organoid 1070:1077 arg1 cells 1079:1083 human lung organoid cells 1059:1083 human lung organoid cells 1059:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35313591 4 76 from roles 615:619 arg1 packaging 662:670 viral packaging 656:670 viral packaging 656:670 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 4 76 from roles 615:619 arg1 transcription 637:649 transcription 637:649 transcription 637:649 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35313591 4 76 from roles 615:619 arg1 replication 624:634 replication 624:634 replication 624:634 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 36992196 6 0 theme nonstructural 1028:1040 arg1 protein 1042:1048 the nonstructural protein 1024:1048 the nonstructural protein (NS)1 of YFV-17D 1024:1065 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 6 0 theme nonstructural 1028:1040 arg1 NS 1051:1052 NS 1051:1052 NS 1051:1052 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 7 1 theme 70 1177:1178 arg1 % 1179:1179 % 1179:1179 % 1179:1179 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 5 2 dep virus 759:763 arg1 strain 777:782 vaccine 17D strain 765:782 the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) 726:792 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 2 dep virus 759:763 arg1 YFV-17D 785:791 YFV-17D 785:791 YFV-17D 785:791 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 7 3 theme two-dose 1252:1259 arg1 regimen 1261:1267 a homologous two-dose regimen 1239:1267 a homologous two-dose regimen 1239:1267 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 5 4 theme fever 753:757 arg1 virus 759:763 the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) 726:792 the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) 726:792 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 9 5 theme vaccine 1606:1612 arg1 candidate 1614:1622 this live-attenuated chimeric YFV-17D-POWV vaccine candidate 1563:1622 this live-attenuated chimeric YFV-17D-POWV vaccine candidate 1563:1622 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 2 6 theme strategies 308:317 arg1 lack 276:279 The lack 272:279 The lack of treatment or prevention strategies for POWV disease 272:334 The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. 36992196 5 7 theme structural 821:830 arg1 genes 832:836 the structural genes pre-membrane (prM) and envelope (E) 817:872 the structural genes pre-membrane (prM) and envelope (E) of POWV 817:880 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 7 theme structural 821:830 arg1 prM 852:854 pre-membrane (prM) 838:855 pre-membrane (prM) 838:855 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 7 theme structural 821:830 arg1 E 871:871 envelope (E) 861:872 envelope (E) 861:872 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 6 8 theme chimeric 887:894 arg1 candidate 917:925 The chimeric YFV-17D-POWV vaccine candidate 883:925 The chimeric YFV-17D-POWV vaccine candidate 883:925 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 4 9 theme host 618:621 arg1 protein 680:686 the zinc-finger antiviral protein 654:686 the zinc-finger antiviral protein (ZAP) 654:692 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 4 9 theme host 618:621 arg1 factors 637:643 host innate immune factors 618:643 host innate immune factors 618:643 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 1 10 theme emerging 202:209 arg1 virus 183:187 Powassan virus 174:187 Powassan virus (POWV) 174:194 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 1 10 theme emerging 202:209 arg1 virus 222:226 an emerging tick-borne virus 199:226 an emerging tick-borne virus 199:226 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 9 11 theme EDIII 1632:1636 arg1 protein 1638:1644 an EDIII protein boost 1629:1650 an EDIII protein boost 1629:1650 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 8 12 theme chimeric 1382:1389 arg1 virus 1391:1395 the initial chimeric virus 1370:1395 the initial chimeric virus 1370:1395 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 4 13 theme immune 630:635 arg1 protein 680:686 the zinc-finger antiviral protein 654:686 the zinc-finger antiviral protein (ZAP) 654:692 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 4 13 theme immune 630:635 arg1 factors 637:643 host innate immune factors 618:643 host innate immune factors 618:643 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 7 14 theme chimeric 1089:1096 arg1 candidate 1106:1114 This live-attenuated chimeric vaccine candidate 1068:1114 This live-attenuated chimeric vaccine candidate 1068:1114 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 9 15 theme further 1660:1666 arg1 studies 1668:1674 further studies 1660:1674 further studies for the development of an effective vaccine strategy for the prevention of POWV disease 1660:1762 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 8 16 theme vaccination 1324:1334 arg1 scheme 1336:1341 a heterologous prime-boost vaccination scheme 1297:1341 a heterologous prime-boost vaccination scheme 1297:1341 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 1 17 from cause 232:236 arg1 humans 264:269 humans 264:269 humans 264:269 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 6 18 theme in 954:955 arg1 application 962:972 in vivo application 954:972 in vivo application 954:972 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 4 19 theme zinc-finger 658:668 arg1 ZAP 689:691 ZAP 689:691 ZAP 689:691 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 4 19 theme zinc-finger 658:668 arg1 protein 680:686 the zinc-finger antiviral protein 654:686 the zinc-finger antiviral protein (ZAP) 654:692 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 9 20 dep protein 1638:1644 arg1 boost 1646:1650 boost 1646:1650 boost 1646:1650 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 7 21 theme vaccine 1098:1104 arg1 candidate 1106:1114 This live-attenuated chimeric vaccine candidate 1068:1114 This live-attenuated chimeric vaccine candidate 1068:1114 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 5 22 theme pre-membrane 838:849 arg1 genes 832:836 the structural genes pre-membrane (prM) and envelope (E) 817:872 the structural genes pre-membrane (prM) and envelope (E) of POWV 817:880 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 22 theme pre-membrane 838:849 arg1 prM 852:854 pre-membrane (prM) 838:855 pre-membrane (prM) 838:855 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 4 23 theme POWV 482:485 arg1 genome 487:492 the POWV genome 478:492 the POWV genome 478:492 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 0 24 theme Prime-Boost 96:106 arg1 Strategy 108:115 an Efficacious Prime-Boost Strategy 81:115 an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model 81:171 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 8 25 theme envelope 1438:1445 arg1 domain 1455:1460 the envelope protein domain III 1434:1464 the envelope protein domain III (EDIII) 1434:1472 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 8 25 theme envelope 1438:1445 arg1 EDIII 1467:1471 EDIII 1467:1471 EDIII 1467:1471 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 7 26 theme POWV 1150:1153 arg1 disease 1155:1161 POWV disease 1150:1161 POWV disease 1150:1161 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 6 27 theme vaccine 909:915 arg1 candidate 917:925 The chimeric YFV-17D-POWV vaccine candidate 883:925 The chimeric YFV-17D-POWV vaccine candidate 883:925 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 9 28 theme vaccine 1712:1718 arg1 strategy 1720:1727 an effective vaccine strategy 1699:1727 an effective vaccine strategy for the prevention of POWV disease 1699:1762 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 0 29 theme Powassan 132:139 arg1 Disease 147:153 Powassan Virus Disease 132:153 Powassan Virus Disease in a Murine Model 132:171 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 0 30 theme Vaccine 51:57 arg1 Candidates 59:68 Live-Attenuated Powassan Virus Vaccine Candidates 20:68 Live-Attenuated Powassan Virus Vaccine Candidates 20:68 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 6 31 dep in 954:955 arg1 vivo 957:960 vivo 957:960 vivo 957:960 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 8 32 theme heterologous 1299:1310 arg1 scheme 1336:1341 a heterologous prime-boost vaccination scheme 1297:1341 a heterologous prime-boost vaccination scheme 1297:1341 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 3 33 theme independent 406:416 arg1 approaches 418:427 two independent approaches 402:427 two independent approaches 402:427 Here, we took two independent approaches to develop vaccine candidates. 36992196 9 34 theme chimeric 1584:1591 arg1 candidate 1614:1622 this live-attenuated chimeric YFV-17D-POWV vaccine candidate 1563:1622 this live-attenuated chimeric YFV-17D-POWV vaccine candidate 1563:1622 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 6 35 theme N-linked 989:996 arg1 site 1012:1015 an N-linked glycosylation site 986:1015 an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D 986:1065 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 4 36 theme CpG 538:540 arg1 frequencies 523:533 the dinucleotide frequencies 506:533 the dinucleotide frequencies of CpG and UpA 506:548 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 5 37 dep genes 832:836 arg1 E 871:871 envelope (E) 861:872 envelope (E) 861:872 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 37 dep genes 832:836 arg1 prM 852:854 pre-membrane (prM) 838:855 pre-membrane (prM) 838:855 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 37 dep genes 832:836 arg1 genes 832:836 the structural genes pre-membrane (prM) and envelope (E) 817:872 the structural genes pre-membrane (prM) and envelope (E) of POWV 817:880 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 0 38 theme Live-Attenuated 20:34 arg1 Candidates 59:68 Live-Attenuated Powassan Virus Vaccine Candidates 20:68 Live-Attenuated Powassan Virus Vaccine Candidates 20:68 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 5 39 theme POWV 877:880 arg1 genes 832:836 the structural genes pre-membrane (prM) and envelope (E) 817:872 the structural genes pre-membrane (prM) and envelope (E) of POWV 817:880 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 39 theme POWV 877:880 arg1 prM 852:854 pre-membrane (prM) 838:855 pre-membrane (prM) 838:855 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 39 theme POWV 877:880 arg1 E 871:871 envelope (E) 861:872 envelope (E) 861:872 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 7 40 theme homologous 1241:1250 arg1 regimen 1261:1267 a homologous two-dose regimen 1239:1267 a homologous two-dose regimen 1239:1267 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 9 41 theme POWV 1751:1754 arg1 disease 1756:1762 POWV disease 1751:1762 POWV disease 1751:1762 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 4 42 theme UpA 546:548 arg1 frequencies 523:533 the dinucleotide frequencies 506:533 the dinucleotide frequencies of CpG and UpA 506:548 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 3 43 theme vaccine 440:446 arg1 candidates 448:457 vaccine candidates 440:457 vaccine candidates 440:457 Here, we took two independent approaches to develop vaccine candidates. 36992196 7 44 theme live-attenuated 1073:1087 arg1 candidate 1106:1114 This live-attenuated chimeric vaccine candidate 1068:1114 This live-attenuated chimeric vaccine candidate 1068:1114 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 0 45 theme Virus 45:49 arg1 Candidates 59:68 Live-Attenuated Powassan Virus Vaccine Candidates 20:68 Live-Attenuated Powassan Virus Vaccine Candidates 20:68 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 5 46 theme vaccine 765:771 arg1 strain 777:782 vaccine 17D strain 765:782 the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) 726:792 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 46 theme vaccine 765:771 arg1 YFV-17D 785:791 YFV-17D 785:791 YFV-17D 785:791 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 8 47 theme mice 1487:1490 arg1 % 1478:1478 100% 1475:1478 100% of the mice 1475:1490 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 8 47 theme mice 1487:1490 arg1 mice 1487:1490 the mice 1483:1490 the mice 1483:1490 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 7 48 theme lethal 1201:1206 arg1 challenge 1208:1216 lethal challenge 1201:1216 lethal challenge 1201:1216 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 8 49 theme initial 1374:1380 arg1 virus 1391:1395 the initial chimeric virus 1370:1395 the initial chimeric virus 1370:1395 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 2 50 theme effective 364:372 arg1 vaccine 379:385 an effective POWV vaccine 361:385 an effective POWV vaccine 361:385 The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. 36992196 0 51 from Disease 147:153 arg1 Model 167:171 a Murine Model 158:171 a Murine Model 158:171 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 6 52 link N-linked 989:996 arg1 site 1012:1015 an N-linked glycosylation site 986:1015 an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D 986:1065 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 9 53 with Combinations 1547:1558 arg1 protein 1638:1644 an EDIII protein boost 1629:1650 an EDIII protein boost 1629:1650 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 1 54 theme encephalitis 248:259 arg1 virus 183:187 Powassan virus 174:187 Powassan virus (POWV) 174:194 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 1 54 theme encephalitis 248:259 arg1 cause 232:236 cause 232:236 cause of lethal encephalitis in humans 232:269 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 1 54 theme encephalitis 248:259 arg1 virus 222:226 an emerging tick-borne virus 199:226 an emerging tick-borne virus 199:226 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 7 55 theme % 1179:1179 arg1 rate 1190:1193 a 70% survival rate 1175:1193 a 70% survival rate 1175:1193 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 2 56 theme treatment 284:292 arg1 strategies 308:317 treatment or prevention strategies 284:317 strategies 308:317 The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. 36992196 9 57 theme live-attenuated 1568:1582 arg1 candidate 1614:1622 this live-attenuated chimeric YFV-17D-POWV vaccine candidate 1563:1622 this live-attenuated chimeric YFV-17D-POWV vaccine candidate 1563:1622 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 8 58 theme morbidity 1536:1544 arg1 signs 1527:1531 any signs 1523:1531 any signs of morbidity 1523:1544 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 0 59 theme Candidates 59:68 arg1 Characterization 0:15 Characterization 0:15 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates 0:68 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 9 60 theme YFV-17D-POWV 1593:1604 arg1 candidate 1614:1622 this live-attenuated chimeric YFV-17D-POWV vaccine candidate 1563:1622 this live-attenuated chimeric YFV-17D-POWV vaccine candidate 1563:1622 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 5 61 theme live-attenuated 730:744 arg1 virus 759:763 the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) 726:792 the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) 726:792 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 6 62 theme YFV-17D-POWV 896:907 arg1 candidate 917:925 The chimeric YFV-17D-POWV vaccine candidate 883:925 The chimeric YFV-17D-POWV vaccine candidate 883:925 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 9 63 theme candidate 1614:1622 arg1 Combinations 1547:1558 Combinations 1547:1558 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost 1547:1650 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 2 64 theme prevention 297:306 arg1 strategies 308:317 treatment or prevention strategies 284:317 strategies 308:317 The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. 36992196 6 65 theme YFV-17D 1059:1065 arg1 protein 1042:1048 the nonstructural protein 1024:1048 the nonstructural protein (NS)1 of YFV-17D 1024:1065 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 6 65 theme YFV-17D 1059:1065 arg1 NS 1051:1052 NS 1051:1052 NS 1051:1052 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 0 66 theme Murine 160:165 arg1 Model 167:171 a Murine Model 158:171 a Murine Model 158:171 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 1 67 theme tick-borne 211:220 arg1 virus 183:187 Powassan virus 174:187 Powassan virus (POWV) 174:194 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 1 67 theme tick-borne 211:220 arg1 virus 222:226 an emerging tick-borne virus 199:226 an emerging tick-borne virus 199:226 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 4 68 theme innate 623:628 arg1 protein 680:686 the zinc-finger antiviral protein 654:686 the zinc-finger antiviral protein (ZAP) 654:692 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 4 68 theme innate 623:628 arg1 factors 637:643 host innate immune factors 618:643 host innate immune factors 618:643 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 1 69 from virus 222:226 arg1 humans 264:269 humans 264:269 humans 264:269 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 7 70 from disease 1155:1161 arg1 mice 1140:1143 mice 1140:1143 mice 1140:1143 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 8 71 with vaccination 1353:1363 arg1 virus 1391:1395 the initial chimeric virus 1370:1395 the initial chimeric virus 1370:1395 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 5 72 theme envelope 861:868 arg1 E 871:871 envelope (E) 861:872 envelope (E) 861:872 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 72 theme envelope 861:868 arg1 genes 832:836 the structural genes pre-membrane (prM) and envelope (E) 817:872 the structural genes pre-membrane (prM) and envelope (E) of POWV 817:880 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 0 73 theme Efficacious 84:94 arg1 Strategy 108:115 an Efficacious Prime-Boost Strategy 81:115 an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model 81:171 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 1 74 theme Powassan 174:181 arg1 virus 222:226 an emerging tick-borne virus 199:226 an emerging tick-borne virus 199:226 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 1 74 theme Powassan 174:181 arg1 POWV 190:193 POWV 190:193 POWV 190:193 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 1 74 theme Powassan 174:181 arg1 virus 183:187 Powassan virus 174:187 Powassan virus (POWV) 174:194 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36992196 8 75 theme protein 1447:1453 arg1 domain 1455:1460 the envelope protein domain III 1434:1464 the envelope protein domain III (EDIII) 1434:1472 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 8 75 theme protein 1447:1453 arg1 EDIII 1467:1471 EDIII 1467:1471 EDIII 1467:1471 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 4 76 theme antiviral 670:678 arg1 ZAP 689:691 ZAP 689:691 ZAP 689:691 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 4 76 theme antiviral 670:678 arg1 protein 680:686 the zinc-finger antiviral protein 654:686 the zinc-finger antiviral protein (ZAP) 654:692 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 9 77 theme effective 1702:1710 arg1 strategy 1720:1727 an effective vaccine strategy 1699:1727 an effective vaccine strategy for the prevention of POWV disease 1699:1762 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 0 78 theme Virus 141:145 arg1 Disease 147:153 Powassan Virus Disease 132:153 Powassan Virus Disease in a Murine Model 132:171 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 9 79 theme strategy 1720:1727 arg1 development 1684:1694 the development 1680:1694 the development of an effective vaccine strategy for the prevention of POWV disease 1680:1762 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 5 80 theme 17D 773:775 arg1 strain 777:782 vaccine 17D strain 765:782 the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) 726:792 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 80 theme 17D 773:775 arg1 YFV-17D 785:791 YFV-17D 785:791 YFV-17D 785:791 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 6 81 theme glycosylation 998:1010 arg1 site 1012:1015 an N-linked glycosylation site 986:1015 an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D 986:1065 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 2 82 theme POWV 374:377 arg1 vaccine 379:385 an effective POWV vaccine 361:385 an effective POWV vaccine 361:385 The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. 36992196 0 83 theme Powassan 36:43 arg1 Candidates 59:68 Live-Attenuated Powassan Virus Vaccine Candidates 20:68 Live-Attenuated Powassan Virus Vaccine Candidates 20:68 Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model. 36992196 8 84 dep protein 1415:1421 arg1 boost 1423:1427 boost 1423:1427 boost 1423:1427 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 8 85 theme prime-boost 1312:1322 arg1 scheme 1336:1341 a heterologous prime-boost vaccination scheme 1297:1341 a heterologous prime-boost vaccination scheme 1297:1341 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 5 86 theme yellow 746:751 arg1 virus 759:763 the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) 726:792 the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) 726:792 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 9 87 theme disease 1756:1762 arg1 prevention 1737:1746 the prevention 1733:1746 the prevention of POWV disease 1733:1762 Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease. 36992196 4 88 theme dinucleotide 510:521 arg1 frequencies 523:533 the dinucleotide frequencies 506:533 the dinucleotide frequencies of CpG and UpA 506:548 First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). 36992196 5 89 theme virus 759:763 arg1 vector 799:804 a vector 797:804 a vector 797:804 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 5 89 theme virus 759:763 arg1 advantage 713:721 advantage 713:721 advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) 713:792 Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. 36992196 6 90 gly glycosylation 998:1010 arg2 site 1012:1015 an N-linked glycosylation site 986:1015 an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D 986:1065 The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. 36992196 2 91 theme POWV 323:326 arg1 disease 328:334 POWV disease 323:334 POWV disease 323:334 The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. 36992196 7 92 theme survival 1181:1188 arg1 rate 1190:1193 a 70% survival rate 1175:1193 a 70% survival rate 1175:1193 This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. 36992196 8 93 with protein 1415:1421 arg1 domain 1455:1460 the envelope protein domain III 1434:1464 the envelope protein domain III (EDIII) 1434:1472 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 8 93 with protein 1415:1421 arg1 EDIII 1467:1471 EDIII 1467:1471 EDIII 1467:1471 Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. 36992196 1 94 theme lethal 241:246 arg1 encephalitis 248:259 lethal encephalitis 241:259 lethal encephalitis 241:259 Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. 36977230 9 0 from safety 1521:1526 arg1 pigs 1554:1557 pigs 1554:1557 pigs 1554:1557 In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs. 36977230 4 1 theme normal 804:809 arg1 range 811:815 the normal range 800:815 the normal range 800:815 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 4 2 theme recombinant 655:665 arg1 group 673:677 The recombinant virus group 651:677 The recombinant virus group 651:677 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 0 3 with Candidate 148:156 arg1 Ability 167:173 the Ability to Produce High Levels of Neutralizing Antibody 163:221 the Ability to Produce High Levels of Neutralizing Antibody 163:221 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 2 4 theme serine 474:479 arg1 substitution 485:496 serine (S) substitution 474:496 serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1 474:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 2 5 theme lineage-1 558:566 arg1 lineage-1 558:566 PRRSV-2 lineage-1 550:566 PRRSV-2 lineage-1 550:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 2 5 theme lineage-1 558:566 arg1 ectodomain 536:545 the GP5 ectodomain 528:545 the GP5 ectodomain of PRRSV-2 lineage-1 528:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 7 6 theme recombinant 1123:1133 arg1 virus 1135:1139 the recombinant virus 1119:1139 the recombinant virus 1119:1139 Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. 36977230 1 7 theme GP5 250:252 arg1 epitopes 267:274 GP5 neutralizing epitopes 250:274 GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) 250:337 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 0 8 theme Amino 98:102 arg1 Acid 104:107 the 44th Amino Acid 89:107 the 44th Amino Acid of GP5 89:114 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 7 9 theme antibody 1207:1214 arg1 ± 1154:1154 4.50 ± 3.00 1149:1159 4.50 ± 3.00 (log2) 1149:1166 Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. 36977230 7 9 theme antibody 1207:1214 arg1 log2 1162:1165 log2 1162:1165 log2 1162:1165 Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. 36977230 7 9 theme antibody 1207:1214 arg1 ± 1177:1177 8.25 ± 0.96 1172:1182 8.25 ± 0.96 (log2) of neutralizing antibody 1172:1214 Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. 36977230 7 9 theme antibody 1207:1214 arg1 log2 1185:1188 log2 1185:1188 log2 1185:1188 Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. 36977230 2 10 theme PRRSV-2 550:556 arg1 lineage-1 558:566 PRRSV-2 lineage-1 550:566 PRRSV-2 lineage-1 550:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 0 11 theme Antibody 214:221 arg1 Levels 191:196 High Levels 186:196 High Levels of Neutralizing Antibody 186:221 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 1 12 theme neutralizing 254:265 arg1 epitopes 267:274 GP5 neutralizing epitopes 250:274 GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) 250:337 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 0 13 theme 44th 93:96 arg1 Acid 104:107 the 44th Amino Acid 89:107 the 44th Amino Acid of GP5 89:114 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 9 14 theme good 1516:1519 arg1 safety 1521:1526 good safety 1516:1526 good safety 1516:1526 In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs. 36977230 8 15 theme neutralizing 1371:1382 arg1 antibodies 1384:1393 neutralizing antibodies 1371:1393 neutralizing antibodies 1371:1393 Taken together, this study confirmed that N44S substitution can create an infectious PRRSV that strongly induces neutralizing antibodies. 36977230 0 16 theme High 186:189 arg1 Levels 191:196 High Levels 186:196 High Levels of Neutralizing Antibody 186:221 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 1 17 link N-linked 224:231 arg1 glycans 233:239 N-linked glycans 224:239 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) 224:337 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 1 17 link N-linked 224:231 arg1 sheath 370:375 a sheath 368:375 a sheath blocking the production of neutralizing antibodies 368:426 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 6 18 theme control 1057:1063 arg1 group 1065:1069 the negative control group 1044:1069 the negative control group 1044:1069 The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). 36977230 6 19 theme rectal 981:986 arg1 temperature 988:998 lower rectal temperature 975:998 lower rectal temperature 975:998 The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). 36977230 9 20 contain have 1469:1472 arg2 candidate 1497:1505 a vaccine candidate 1487:1505 a vaccine candidate 1487:1505 In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs. 36977230 9 20 contain have 1469:1472 arg2 potential 1474:1482 potential 1474:1482 potential 1474:1482 In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs. 36977230 9 20 contain have 1469:1472 arg1 mutant 1428:1433 the vCSL1-GP5-N44S mutant 1409:1433 the vCSL1-GP5-N44S mutant that we produced 1409:1450 In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs. 36977230 0 21 theme Neutralizing 201:212 arg1 Antibody 214:221 Neutralizing Antibody 201:221 Neutralizing Antibody 201:221 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 9 22 theme vCSL1-GP5-N44S 1413:1426 arg1 mutant 1428:1433 the vCSL1-GP5-N44S mutant 1409:1433 the vCSL1-GP5-N44S mutant that we produced 1409:1450 In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs. 36977230 6 23 theme negative 1048:1055 arg1 group 1065:1069 the negative control group 1044:1069 the negative control group 1044:1069 The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). 36977230 2 24 theme GP5 532:534 arg1 lineage-1 558:566 PRRSV-2 lineage-1 550:566 PRRSV-2 lineage-1 550:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 2 24 theme GP5 532:534 arg1 ectodomain 536:545 the GP5 ectodomain 528:545 the GP5 ectodomain of PRRSV-2 lineage-1 528:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 6 25 theme lower 975:979 arg1 temperature 988:998 lower rectal temperature 975:998 lower rectal temperature 975:998 The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). 36977230 6 26 theme post-challenge 1083:1096 arg1 days 1078:1081 19 days post-challenge 1075:1096 19 days post-challenge (dpc) 1075:1102 The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). 36977230 6 26 theme post-challenge 1083:1096 arg1 dpc 1099:1101 dpc 1099:1101 dpc 1099:1101 The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). 36977230 9 27 from effects 1543:1549 arg1 pigs 1554:1557 pigs 1554:1557 pigs 1554:1557 In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs. 36977230 0 28 theme Respiratory 25:35 arg1 Virus 46:50 Porcine Reproductive and Respiratory Syndrome Virus 0:50 Virus 46:50 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 1 29 theme porcine 279:285 arg1 epitopes 267:274 GP5 neutralizing epitopes 250:274 GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) 250:337 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 8 30 theme N44S 1300:1303 arg1 substitution 1305:1316 N44S substitution 1300:1316 N44S substitution 1300:1316 Taken together, this study confirmed that N44S substitution can create an infectious PRRSV that strongly induces neutralizing antibodies. 36977230 4 31 theme average 766:772 arg1 gain 787:790 average daily weight gain 766:790 average daily weight gain 766:790 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 4 32 theme days 706:709 arg1 dpi 729:731 dpi 729:731 dpi 729:731 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 4 32 theme days 706:709 arg1 post-inoculation 711:726 42 days post-inoculation 703:726 42 days post-inoculation (dpi) 703:732 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 2 33 theme 44th 505:508 arg1 N 522:522 N 522:522 N 522:522 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 2 33 theme 44th 505:508 arg1 asparagine 510:519 the 44th asparagine 501:519 the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1 501:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 1 34 theme reproductive 287:298 arg1 porcine 279:285 porcine reproductive 279:298 porcine reproductive 279:298 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 0 35 theme GP5 112:114 arg1 Acid 104:107 the 44th Amino Acid 89:107 the 44th Amino Acid of GP5 89:114 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 3 36 theme in 604:605 arg1 experiments 612:622 in vivo experiments 604:622 in vivo experiments 604:622 To evaluate the recombinant PRRSV, in vivo experiments were performed in piglets. 36977230 6 37 theme PRRSV 956:960 arg1 group 962:966 The recombinant PRRSV group 940:966 The recombinant PRRSV group 940:966 The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). 36977230 4 38 theme control 856:862 arg1 group 864:868 the negative control group 843:868 the negative control group 843:868 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 6 39 theme recombinant 944:954 arg1 group 962:966 The recombinant PRRSV group 940:966 The recombinant PRRSV group 940:966 The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). 36977230 0 40 theme Syndrome 37:44 arg1 Virus 46:50 Porcine Reproductive and Respiratory Syndrome Virus 0:50 Virus 46:50 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 1 41 theme respiratory 304:314 arg1 PRRSV 332:336 PRRSV 332:336 PRRSV 332:336 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 1 41 theme respiratory 304:314 arg1 virus 325:329 respiratory syndrome virus 304:329 respiratory syndrome virus (PRRSV) 304:337 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 4 42 theme negative 847:854 arg1 group 864:868 the negative control group 843:868 the negative control group 843:868 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 0 43 from Substitution 73:84 arg1 Acid 104:107 the 44th Amino Acid 89:107 the 44th Amino Acid of GP5 89:114 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 3 44 dep in 604:605 arg1 vivo 607:610 vivo 607:610 vivo 607:610 To evaluate the recombinant PRRSV, in vivo experiments were performed in piglets. 36977230 4 45 theme same 824:827 arg1 point 834:838 the same time point 820:838 the same time point as the negative control group 820:868 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 1 46 theme syndrome 316:323 arg1 PRRSV 332:336 PRRSV 332:336 PRRSV 332:336 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 1 46 theme syndrome 316:323 arg1 virus 325:329 respiratory syndrome virus 304:329 respiratory syndrome virus (PRRSV) 304:337 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 0 47 theme Vaccine 140:146 arg1 Candidate 148:156 a Potential Vaccine Candidate 128:156 a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody 128:221 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 2 48 theme S 482:482 arg1 substitution 485:496 serine (S) substitution 474:496 serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1 474:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 4 49 theme daily 774:778 arg1 gain 787:790 average daily weight gain 766:790 average daily weight gain 766:790 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 1 50 theme virus 325:329 arg1 epitopes 267:274 GP5 neutralizing epitopes 250:274 GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) 250:337 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 0 51 theme Potential 130:138 arg1 Candidate 148:156 a Potential Vaccine Candidate 128:156 a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody 128:221 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 4 52 from point 834:838 arg1 range 811:815 the normal range 800:815 the normal range 800:815 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 4 53 theme weight 780:785 arg1 gain 787:790 average daily weight gain 766:790 average daily weight gain 766:790 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 9 54 theme protective 1532:1541 arg1 effects 1543:1549 protective effects 1532:1549 protective effects 1532:1549 In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs. 36977230 4 55 theme virus 667:671 arg1 group 673:677 The recombinant virus group 651:677 The recombinant virus group 651:677 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 2 56 from substitution 485:496 arg1 N 522:522 N 522:522 N 522:522 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 2 56 from substitution 485:496 arg1 asparagine 510:519 the 44th asparagine 501:519 the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1 501:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 7 57 theme neutralizing 1194:1205 arg1 antibody 1207:1214 neutralizing antibody 1194:1214 neutralizing antibody 1194:1214 Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. 36977230 5 58 theme wild-type 923:931 arg1 virus 933:937 the wild-type virus 919:937 the wild-type virus 919:937 On the 42 dpi, both groups were challenged with the wild-type virus. 36977230 6 59 theme lung 1018:1021 arg1 lesions 1023:1029 the lung lesions 1014:1029 the lung lesions 1014:1029 The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). 36977230 4 60 theme time 829:832 arg1 point 834:838 the same time point 820:838 the same time point as the negative control group 820:868 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 1 61 theme neutralizing 404:415 arg1 antibodies 417:426 neutralizing antibodies 404:426 neutralizing antibodies 404:426 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 3 62 theme recombinant 585:595 arg1 PRRSV 597:601 the recombinant PRRSV 581:601 the recombinant PRRSV 581:601 To evaluate the recombinant PRRSV, in vivo experiments were performed in piglets. 36977230 2 63 from asparagine 510:519 arg1 lineage-1 558:566 PRRSV-2 lineage-1 550:566 PRRSV-2 lineage-1 550:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 2 63 from asparagine 510:519 arg1 ectodomain 536:545 the GP5 ectodomain 528:545 the GP5 ectodomain of PRRSV-2 lineage-1 528:566 Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. 36977230 1 64 theme antibodies 417:426 arg1 production 390:399 the production 386:399 the production of neutralizing antibodies 386:426 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 4 65 theme rectal 743:748 arg1 temperature 750:760 the rectal temperature 739:760 the rectal temperature 739:760 The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. 36977230 1 66 theme N-linked 224:231 arg1 glycans 233:239 N-linked glycans 224:239 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) 224:337 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 1 66 theme N-linked 224:231 arg1 sheath 370:375 a sheath 368:375 a sheath blocking the production of neutralizing antibodies 368:426 N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. 36977230 0 67 theme Serine 66:71 arg1 Substitution 73:84 Serine Substitution 66:84 Serine Substitution on the 44th Amino Acid of GP5 66:114 Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody. 36977230 9 68 theme vaccine 1489:1495 arg1 candidate 1497:1505 a vaccine candidate 1487:1505 a vaccine candidate 1487:1505 In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs. 36977230 9 68 theme vaccine 1489:1495 arg1 potential 1474:1482 potential 1474:1482 potential 1474:1482 In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs. 36977230 7 69 theme 4.50 1149:1152 arg1 ± 1154:1154 4.50 ± 3.00 1149:1159 4.50 ± 3.00 (log2) 1149:1166 Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. 36977230 7 69 theme 4.50 1149:1152 arg1 log2 1162:1165 log2 1162:1165 log2 1162:1165 Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. 36977230 8 70 theme infectious 1332:1341 arg1 PRRSV 1343:1347 an infectious PRRSV 1329:1347 an infectious PRRSV that strongly induces neutralizing antibodies 1329:1393 Taken together, this study confirmed that N44S substitution can create an infectious PRRSV that strongly induces neutralizing antibodies. 36930724 6 0 theme muscular 1035:1042 arg1 hypotonia 1044:1052 muscular hypotonia 1035:1052 muscular hypotonia 1035:1052 Our adolescent and young adult cohort of six patients presented with epilepsy, muscular hypotonia, speech, and developmental delay. 36930724 2 1 theme outcome 159:165 arg1 data 167:170 long-term outcome data 149:170 long-term outcome data 149:170 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 2 2 theme pathogenic 289:298 arg1 variants 300:307 confirmed pathogenic variants 279:307 confirmed pathogenic variants in ALG13 in our own cohort and in the literature 279:356 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 4 3 from variants 666:673 arg1 ALG13 678:682 ALG13 678:682 ALG13 678:682 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36930724 4 4 theme history 803:809 arg1 study 811:815 our natural history study 791:815 our natural history study 791:815 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36930724 4 5 theme confirmed 645:653 arg1 variants 666:673 confirmed pathogenic variants 645:673 confirmed pathogenic variants in ALG13 645:682 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36930724 4 6 dep new 762:764 arg1 unreported 767:776 unreported 767:776 unreported 767:776 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36930724 7 7 located present 1116:1122 arg2 disability 1101:1110 Intellectual disability 1088:1110 Intellectual disability 1088:1110 Intellectual disability was present in all female patients with ALG13-CDG. 36930724 7 7 located present 1116:1122 arg1 patients 1138:1145 all female patients 1127:1145 all female patients with ALG13-CDG 1127:1160 Intellectual disability was present in all female patients with ALG13-CDG. 36930724 8 8 theme severe 1216:1221 arg1 symptoms 1240:1247 severe gastrointestinal symptoms 1216:1247 severe gastrointestinal symptoms 1216:1247 Unreported features included ataxia, neuropathy, and severe gastrointestinal symptoms requiring G/J tube placement. 36930724 3 9 theme females 553:559 arg1 females 553:559 these two females 543:559 these two females 543:559 From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. 36930724 3 9 theme females 553:559 arg1 one 536:538 one 536:538 one 536:538 From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. 36930724 8 10 theme Unreported 1163:1172 arg1 features 1174:1181 Unreported features 1163:1181 Unreported features 1163:1181 Unreported features included ataxia, neuropathy, and severe gastrointestinal symptoms requiring G/J tube placement. 36930724 7 11 from patients 1138:1145 arg1 present 1116:1122 present 1116:1122 present 1116:1122 Intellectual disability was present in all female patients with ALG13-CDG. 36930724 2 12 theme reviewed 224:231 arg1 individuals 233:243 reviewed individuals 224:243 reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature 224:356 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 8 13 theme G/J 1259:1261 arg1 placement 1268:1276 G/J tube placement 1259:1276 G/J tube placement 1259:1276 Unreported features included ataxia, neuropathy, and severe gastrointestinal symptoms requiring G/J tube placement. 36930724 5 14 with 16 years 909:916 arg1 diagnosis 945:953 a confirmed ALG13-CDG diagnosis 923:953 a confirmed ALG13-CDG diagnosis 923:953 Two male patients have died due to ALG13-CDG, and there were no surviving males older than 16 years with a confirmed ALG13-CDG diagnosis. 36930724 2 15 theme young 258:262 arg1 adulthood 264:272 young adulthood 258:272 young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature 258:356 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 2 16 from variants 300:307 arg1 literature 347:356 the literature 343:356 the literature 343:356 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 2 16 from variants 300:307 arg1 ALG13 312:316 ALG13 312:316 ALG13 in our own cohort 312:334 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 11 17 theme Major 1459:1463 arg1 problems 1472:1479 Major health problems 1459:1479 Major health problems 1459:1479 Major health problems included persistent seizures in three patients. 36930724 2 18 from ALG13 312:316 arg1 cohort 329:334 our own cohort 321:334 our own cohort 321:334 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 12 19 from efficient 1548:1556 arg1 patients 1592:1599 three out of four patients 1574:1599 three out of four patients 1574:1599 Ketogenic diet was efficient for seizures in three out of four patients. 36930724 13 20 theme absent 1692:1697 arg1 speech 1699:1704 mostly absent speech 1685:1704 mostly absent speech 1685:1704 Although all patients were mobile, they all had severe communication problems with mostly absent speech and were unable to function without parental support. 36930724 11 21 theme persistent 1490:1499 arg1 seizures 1501:1508 persistent seizures 1490:1508 persistent seizures in three patients 1490:1526 Major health problems included persistent seizures in three patients. 36930724 7 22 from present 1116:1122 arg1 patients 1138:1145 all female patients 1127:1145 all female patients with ALG13-CDG 1127:1160 Intellectual disability was present in all female patients with ALG13-CDG. 36930724 3 23 theme Disorders 432:440 arg1 Frontiers 408:416 our Frontiers 404:416 our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study 404:490 From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. 36930724 1 24 theme rare 81:84 arg1 disorder 95:102 a rare X-linked disorder 79:102 a rare X-linked disorder of N-linked glycosylation 79:128 ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. 36930724 1 24 theme rare 81:84 arg1 ALG13-CDG 66:74 ALG13-CDG 66:74 ALG13-CDG 66:74 ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. 36930724 3 25 theme ALG13-CDG 371:379 arg1 patients 381:388 the 14 ALG13-CDG patients 364:388 the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study 364:490 From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. 36930724 13 26 theme communication 1657:1669 arg1 problems 1671:1678 severe communication problems 1650:1678 severe communication problems 1650:1678 Although all patients were mobile, they all had severe communication problems with mostly absent speech and were unable to function without parental support. 36930724 0 27 theme Long-term 0:8 arg1 outcomes 10:17 Long-term outcomes 0:17 Long-term outcomes in ALG13-Congenital Disorder of Glycosylation 0:63 Long-term outcomes in ALG13-Congenital Disorder of Glycosylation. 36930724 5 28 theme surviving 882:890 arg1 males 892:896 no surviving males 879:896 no surviving males older than 16 years with a confirmed ALG13-CDG diagnosis 879:953 Two male patients have died due to ALG13-CDG, and there were no surviving males older than 16 years with a confirmed ALG13-CDG diagnosis. 36930724 6 29 theme patients 1001:1008 arg1 cohort 987:992 Our adolescent and young adult cohort 956:992 Our adolescent and young adult cohort of six patients 956:1008 Our adolescent and young adult cohort of six patients presented with epilepsy, muscular hypotonia, speech, and developmental delay. 36930724 3 30 theme natural 470:476 arg1 history 478:484 Glycosylation Consortium natural history 445:484 Glycosylation Consortium natural history study 445:490 From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. 36930724 12 31 from patients 1592:1599 arg1 efficient 1548:1556 efficient 1548:1556 efficient 1548:1556 Ketogenic diet was efficient for seizures in three out of four patients. 36930724 1 32 theme N-linked 107:114 arg1 glycosylation 116:128 N-linked glycosylation 107:128 N-linked glycosylation 107:128 ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. 36930724 14 33 theme skeletal 1833:1840 arg1 involvement 1842:1852 gastrointestinal and skeletal involvement 1812:1852 gastrointestinal and skeletal involvement in addition to a chronic, mostly non-progressive neurologic phenotype 1812:1922 In summary, long-term outcome in ALG13-CDG includes gastrointestinal and skeletal involvement in addition to a chronic, mostly non-progressive neurologic phenotype. 36930724 3 34 theme Glycosylation 445:457 arg1 history 478:484 Glycosylation Consortium natural history 445:484 Glycosylation Consortium natural history study 445:490 From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. 36930724 9 35 theme natural 1314:1320 arg1 study 1330:1334 our natural history study 1310:1334 our natural history study 1310:1334 In addition, two patients from our natural history study developed unilateral hearing loss. 36930724 6 36 theme adult 981:985 arg1 cohort 987:992 Our adolescent and young adult cohort 956:992 Our adolescent and young adult cohort of six patients 956:1008 Our adolescent and young adult cohort of six patients presented with epilepsy, muscular hypotonia, speech, and developmental delay. 36930724 2 37 theme data 167:170 arg1 lack 141:144 the lack 137:144 the lack of long-term outcome data in ALG13-CDG 137:183 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 0 38 theme Glycosylation 51:63 arg1 Disorder 39:46 ALG13-Congenital Disorder 22:46 ALG13-Congenital Disorder of Glycosylation 22:63 Long-term outcomes in ALG13-Congenital Disorder of Glycosylation. 36930724 2 39 theme natural 199:205 arg1 data 215:218 natural history data 199:218 natural history data 199:218 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 3 40 theme study 486:490 arg1 Disorders 432:440 Congenital Disorders 421:440 Congenital Disorders of Glycosylation Consortium natural history study 421:490 From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. 36930724 9 41 theme unilateral 1346:1355 arg1 loss 1365:1368 unilateral hearing loss 1346:1368 unilateral hearing loss 1346:1368 In addition, two patients from our natural history study developed unilateral hearing loss. 36930724 5 42 theme ALG13-CDG 935:943 arg1 diagnosis 945:953 a confirmed ALG13-CDG diagnosis 923:953 a confirmed ALG13-CDG diagnosis 923:953 Two male patients have died due to ALG13-CDG, and there were no surviving males older than 16 years with a confirmed ALG13-CDG diagnosis. 36930724 10 43 located found 1399:1403 arg1 patients 1413:1420 four patients 1408:1420 four patients 1408:1420 Skeletal abnormalities were found in four patients, including osteopenia and scoliosis. 36930724 10 43 located found 1399:1403 arg2 abnormalities 1380:1392 Skeletal abnormalities 1371:1392 Skeletal abnormalities 1371:1392 Skeletal abnormalities were found in four patients, including osteopenia and scoliosis. 36930724 5 44 theme male 822:825 arg1 patients 827:834 Two male patients 818:834 Two male patients 818:834 Two male patients have died due to ALG13-CDG, and there were no surviving males older than 16 years with a confirmed ALG13-CDG diagnosis. 36930724 1 45 link X-linked 86:93 arg1 disorder 95:102 a rare X-linked disorder 79:102 a rare X-linked disorder of N-linked glycosylation 79:128 ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. 36930724 1 45 link X-linked 86:93 arg1 ALG13-CDG 66:74 ALG13-CDG 66:74 ALG13-CDG 66:74 ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. 36930724 2 46 theme long-term 149:157 arg1 data 167:170 long-term outcome data 149:170 long-term outcome data 149:170 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 2 47 theme confirmed 279:287 arg1 variants 300:307 confirmed pathogenic variants 279:307 confirmed pathogenic variants in ALG13 in our own cohort and in the literature 279:356 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 4 48 theme natural 795:801 arg1 study 811:815 our natural history study 791:815 our natural history study 791:815 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36930724 2 49 theme history 207:213 arg1 data 215:218 natural history data 199:218 natural history data 199:218 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 4 50 theme pathogenic 655:664 arg1 variants 666:673 confirmed pathogenic variants 645:673 confirmed pathogenic variants in ALG13 645:682 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36930724 13 51 theme parental 1742:1749 arg1 support 1751:1757 parental support 1742:1757 parental support 1742:1757 Although all patients were mobile, they all had severe communication problems with mostly absent speech and were unable to function without parental support. 36930724 10 52 theme Skeletal 1371:1378 arg1 abnormalities 1380:1392 Skeletal abnormalities 1371:1392 Skeletal abnormalities 1371:1392 Skeletal abnormalities were found in four patients, including osteopenia and scoliosis. 36930724 4 53 dep patient 778:784 arg1 addition 746:753 addition 746:753 addition 746:753 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36930724 2 54 from lack 141:144 arg1 ALG13-CDG 175:183 ALG13-CDG 175:183 ALG13-CDG 175:183 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 7 55 with patients 1138:1145 arg1 ALG13-CDG 1152:1160 ALG13-CDG 1152:1160 ALG13-CDG 1152:1160 Intellectual disability was present in all female patients with ALG13-CDG. 36930724 8 56 theme gastrointestinal 1223:1238 arg1 symptoms 1240:1247 severe gastrointestinal symptoms 1216:1247 severe gastrointestinal symptoms 1216:1247 Unreported features included ataxia, neuropathy, and severe gastrointestinal symptoms requiring G/J tube placement. 36930724 1 57 theme glycosylation 116:128 arg1 disorder 95:102 a rare X-linked disorder 79:102 a rare X-linked disorder of N-linked glycosylation 79:128 ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. 36930724 1 57 theme glycosylation 116:128 arg1 ALG13-CDG 66:74 ALG13-CDG 66:74 ALG13-CDG 66:74 ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. 36930724 2 58 with adulthood 264:272 arg1 variants 300:307 confirmed pathogenic variants 279:307 confirmed pathogenic variants in ALG13 in our own cohort and in the literature 279:356 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 11 59 theme health 1465:1470 arg1 problems 1472:1479 Major health problems 1459:1479 Major health problems 1459:1479 Major health problems included persistent seizures in three patients. 36930724 8 60 theme tube 1263:1266 arg1 placement 1268:1276 G/J tube placement 1259:1276 G/J tube placement 1259:1276 Unreported features included ataxia, neuropathy, and severe gastrointestinal symptoms requiring G/J tube placement. 36930724 5 61 theme older 898:902 arg1 males 892:896 no surviving males 879:896 no surviving males older than 16 years with a confirmed ALG13-CDG diagnosis 879:953 Two male patients have died due to ALG13-CDG, and there were no surviving males older than 16 years with a confirmed ALG13-CDG diagnosis. 36930724 6 62 theme adolescent 960:969 arg1 cohort 987:992 Our adolescent and young adult cohort 956:992 Our adolescent and young adult cohort of six patients 956:1008 Our adolescent and young adult cohort of six patients presented with epilepsy, muscular hypotonia, speech, and developmental delay. 36930724 9 63 from study 1330:1334 arg1 patients 1296:1303 two patients 1292:1303 two patients from our natural history study 1292:1334 In addition, two patients from our natural history study developed unilateral hearing loss. 36930724 14 64 theme gastrointestinal 1812:1827 arg1 involvement 1842:1852 gastrointestinal and skeletal involvement 1812:1852 gastrointestinal and skeletal involvement in addition to a chronic, mostly non-progressive neurologic phenotype 1812:1922 In summary, long-term outcome in ALG13-CDG includes gastrointestinal and skeletal involvement in addition to a chronic, mostly non-progressive neurologic phenotype. 36930724 0 65 from outcomes 10:17 arg1 Disorder 39:46 ALG13-Congenital Disorder 22:46 ALG13-Congenital Disorder of Glycosylation 22:63 Long-term outcomes in ALG13-Congenital Disorder of Glycosylation. 36930724 13 66 contain had 1646:1648 arg2 problems 1671:1678 severe communication problems 1650:1678 severe communication problems 1650:1678 Although all patients were mobile, they all had severe communication problems with mostly absent speech and were unable to function without parental support. 36930724 13 66 contain had 1646:1648 arg1 they 1637:1640 they 1637:1640 they 1637:1640 Although all patients were mobile, they all had severe communication problems with mostly absent speech and were unable to function without parental support. 36930724 12 67 theme Ketogenic 1529:1537 arg1 diet 1539:1542 Ketogenic diet 1529:1542 Ketogenic diet 1529:1542 Ketogenic diet was efficient for seizures in three out of four patients. 36930724 7 68 theme female 1131:1136 arg1 patients 1138:1145 all female patients 1127:1145 all female patients with ALG13-CDG 1127:1160 Intellectual disability was present in all female patients with ALG13-CDG. 36930724 4 69 from study 811:815 arg1 patient 778:784 the new, unreported patient 758:784 the new, unreported patient from our natural history study 758:815 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36930724 11 70 from seizures 1501:1508 arg1 patients 1519:1526 three patients 1513:1526 three patients 1513:1526 Major health problems included persistent seizures in three patients. 36930724 13 71 theme severe 1650:1655 arg1 problems 1671:1678 severe communication problems 1650:1678 severe communication problems 1650:1678 Although all patients were mobile, they all had severe communication problems with mostly absent speech and were unable to function without parental support. 36930724 14 72 from outcome 1782:1788 arg1 ALG13-CDG 1793:1801 ALG13-CDG 1793:1801 ALG13-CDG 1793:1801 In summary, long-term outcome in ALG13-CDG includes gastrointestinal and skeletal involvement in addition to a chronic, mostly non-progressive neurologic phenotype. 36930724 1 73 theme X-linked 86:93 arg1 disorder 95:102 a rare X-linked disorder 79:102 a rare X-linked disorder of N-linked glycosylation 79:128 ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. 36930724 1 73 theme X-linked 86:93 arg1 ALG13-CDG 66:74 ALG13-CDG 66:74 ALG13-CDG 66:74 ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. 36930724 7 74 attach present 1116:1122 arg2 disability 1101:1110 Intellectual disability 1088:1110 Intellectual disability 1088:1110 Intellectual disability was present in all female patients with ALG13-CDG. 36930724 7 74 attach present 1116:1122 arg1 patients 1138:1145 all female patients 1127:1145 all female patients with ALG13-CDG 1127:1160 Intellectual disability was present in all female patients with ALG13-CDG. 36930724 3 75 theme Congenital 421:430 arg1 Disorders 432:440 Congenital Disorders 421:440 Congenital Disorders of Glycosylation Consortium natural history study 421:490 From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. 36930724 0 76 theme ALG13-Congenital 22:37 arg1 Disorder 39:46 ALG13-Congenital Disorder 22:46 ALG13-Congenital Disorder of Glycosylation 22:63 Long-term outcomes in ALG13-Congenital Disorder of Glycosylation. 36930724 3 77 theme history 478:484 arg1 study 486:490 Glycosylation Consortium natural history study 445:490 Glycosylation Consortium natural history study 445:490 From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. 36930724 7 78 theme Intellectual 1088:1099 arg1 disability 1101:1110 Intellectual disability 1088:1110 Intellectual disability 1088:1110 Intellectual disability was present in all female patients with ALG13-CDG. 36930724 14 79 theme long-term 1772:1780 arg1 outcome 1782:1788 long-term outcome 1772:1788 long-term outcome in ALG13-CDG 1772:1801 In summary, long-term outcome in ALG13-CDG includes gastrointestinal and skeletal involvement in addition to a chronic, mostly non-progressive neurologic phenotype. 36930724 14 80 theme chronic 1871:1877 arg1 phenotype 1914:1922 a chronic, mostly non-progressive neurologic phenotype 1869:1922 a chronic, mostly non-progressive neurologic phenotype 1869:1922 In summary, long-term outcome in ALG13-CDG includes gastrointestinal and skeletal involvement in addition to a chronic, mostly non-progressive neurologic phenotype. 36930724 14 81 dep chronic 1871:1877 arg1 neurologic 1903:1912 neurologic 1903:1912 neurologic 1903:1912 In summary, long-term outcome in ALG13-CDG includes gastrointestinal and skeletal involvement in addition to a chronic, mostly non-progressive neurologic phenotype. 36930724 3 82 theme Consortium 459:468 arg1 history 478:484 Glycosylation Consortium natural history 445:484 Glycosylation Consortium natural history study 445:490 From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. 36930724 9 83 theme history 1322:1328 arg1 study 1330:1334 our natural history study 1310:1334 our natural history study 1310:1334 In addition, two patients from our natural history study developed unilateral hearing loss. 36930724 6 84 theme developmental 1067:1079 arg1 delay 1081:1085 developmental delay 1067:1085 developmental delay 1067:1085 Our adolescent and young adult cohort of six patients presented with epilepsy, muscular hypotonia, speech, and developmental delay. 36930724 4 85 with literature 629:638 arg1 variants 666:673 confirmed pathogenic variants 645:673 confirmed pathogenic variants in ALG13 645:682 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36930724 5 86 theme confirmed 925:933 arg1 diagnosis 945:953 a confirmed ALG13-CDG diagnosis 923:953 a confirmed ALG13-CDG diagnosis 923:953 Two male patients have died due to ALG13-CDG, and there were no surviving males older than 16 years with a confirmed ALG13-CDG diagnosis. 36930724 2 87 theme own 325:327 arg1 cohort 329:334 our own cohort 321:334 our own cohort 321:334 Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. 36930724 9 88 theme hearing 1357:1363 arg1 loss 1365:1368 unilateral hearing loss 1346:1368 unilateral hearing loss 1346:1368 In addition, two patients from our natural history study developed unilateral hearing loss. 36930724 4 89 theme medical 621:627 arg1 literature 629:638 the medical literature 617:638 the medical literature with confirmed pathogenic variants in ALG13 617:682 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36930724 1 90 link N-linked 107:114 arg1 glycosylation 116:128 N-linked glycosylation 107:128 N-linked glycosylation 107:128 ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. 36930724 4 91 theme new 762:764 arg1 patient 778:784 the new, unreported patient 758:784 the new, unreported patient from our natural history study 758:815 From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. 36900350 9 0 theme multi-platform 1580:1593 arg1 analysis 1614:1621 a multi-platform mass-spectrometric analysis 1578:1621 a multi-platform mass-spectrometric analysis 1578:1621 The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients. 36900350 6 1 theme tumor 1044:1048 arg1 samples 1050:1056 tumor samples 1044:1056 tumor samples 1044:1056 Specifically, we observed a general increase in the relative abundance of high-mannose and sialofucosylated N-glycans in tumor samples. 36900350 9 2 theme analysis 1614:1621 arg1 demonstration 1561:1573 the first demonstration 1551:1573 the first demonstration of a multi-platform mass-spectrometric analysis 1551:1621 The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients. 36900350 2 3 used used 377:380 arg2 biomarkers 317:326 potential biomarkers 307:326 potential biomarkers 307:326 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 2 3 used used 377:380 arg2 tools 396:400 diagnostic tools 385:400 diagnostic tools against NSCLC 385:414 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 2 3 used used 377:380 arg2 glycans 337:343 glycans 337:343 glycans 337:343 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 2 3 used used 377:380 arg2 glycoproteins 349:361 glycoproteins 349:361 glycoproteins 349:361 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 3 4 theme N-glycosylation 452:466 arg1 maps 481:484 the N-glycome, proteome, and N-glycosylation distribution maps 423:484 maps 481:484 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 4 5 theme three-gene 728:737 arg1 panel 739:743 a three-gene panel 726:743 a three-gene panel (CD133, KRT19, and MUC1) 726:768 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 3 6 theme peritumoral 499:509 arg1 tissues 511:517 tumor and peritumoral tissues 489:517 tissues 511:517 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 5 7 from role 869:872 arg1 progression 910:920 cancer progression 903:920 cancer progression 903:920 Although the profiles of each patient were unique, specific trends arose that correlated with the role of aberrant glycosylation in cancer progression. 36900350 1 8 theme leading 164:170 arg1 cancer 150:155 Lung cancer 145:155 Lung cancer 145:155 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 1 8 theme leading 164:170 arg1 cause 172:176 the leading cause 160:176 the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers 160:274 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 9 9 theme lung 1649:1652 arg1 patients 1661:1668 Filipino lung cancer patients 1640:1668 Filipino lung cancer patients 1640:1668 The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients. 36900350 7 10 theme regulatory 1277:1286 arg1 pathways 1288:1295 regulatory pathways 1277:1295 regulatory pathways 1277:1295 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 0 11 theme Series 106:111 arg1 Study 113:117 Case Series Study 101:117 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 0:143 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 3 12 theme tumor 489:493 arg1 tissues 511:517 tumor and peritumoral tissues 489:517 tissues 511:517 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 3 13 theme lung 531:534 arg1 patients 543:550 Filipino lung cancer patients 522:550 Filipino lung cancer patients (n = 5) 522:558 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 3 13 theme lung 531:534 arg1 n 553:553 n = 5 553:557 n = 5 553:557 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 1 14 theme death 188:192 arg1 cancer 150:155 Lung cancer 145:155 Lung cancer 145:155 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 1 14 theme death 188:192 arg1 cause 172:176 the leading cause 160:176 the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers 160:274 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 8 15 theme dysregulated 1359:1370 arg1 proteins 1372:1379 dysregulated proteins 1359:1379 dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation 1359:1463 Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. 36900350 7 16 theme cell 1258:1261 arg1 adhesion 1263:1270 cell adhesion 1258:1270 cell adhesion 1258:1270 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 5 17 theme aberrant 877:884 arg1 glycosylation 886:898 aberrant glycosylation 877:898 aberrant glycosylation 877:898 Although the profiles of each patient were unique, specific trends arose that correlated with the role of aberrant glycosylation in cancer progression. 36900350 4 18 theme cancer 635:640 arg1 I-III 655:659 I-III 655:659 I-III 655:659 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 4 18 theme cancer 635:640 arg1 development 642:652 cancer development 635:652 cancer development (I-III) 635:660 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 4 19 theme case 599:602 arg1 studies 604:610 several case studies 591:610 several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1) 591:768 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 0 20 theme Philippine 53:62 arg1 Cancer 69:74 Philippine Lung Cancer 53:74 Philippine Lung Cancer 53:74 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 3 21 theme patients 543:550 arg1 maps 481:484 the N-glycome, proteome, and N-glycosylation distribution maps 423:484 maps 481:484 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 3 21 theme patients 543:550 arg1 proteome 438:445 the N-glycome, proteome, and N-glycosylation distribution maps 423:484 proteome 438:445 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 4 22 dep status 672:677 arg1 ALK 686:688 ALK 686:688 ALK 686:688 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 4 22 dep status 672:677 arg1 EGFR 680:683 EGFR 680:683 EGFR 680:683 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 0 23 theme Cancer 69:74 arg1 Profiling 40:48 Glycomic, Glycoproteomic, and Proteomic Profiling 0:48 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 0:143 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 7 24 gly glycoproteins 1186:1198 arg1 glycoproteins 1186:1198 glycoproteins 1186:1198 glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways 1186:1295 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 1 25 theme Lung 145:148 arg1 cancer 150:155 Lung cancer 145:155 Lung cancer 145:155 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 1 25 theme Lung 145:148 arg1 cause 172:176 the leading cause 160:176 the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers 160:274 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 8 26 theme cell-ECM 1415:1422 arg1 interactions 1424:1435 cell-ECM interactions 1415:1435 cell-ECM interactions 1415:1435 Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. 36900350 4 27 theme mutation 663:670 arg1 status 672:677 mutation status 663:677 mutation status (EGFR, ALK) 663:689 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 0 28 theme Peritumoral 80:90 arg1 Tissues 92:98 Peritumoral Tissues 80:98 Peritumoral Tissues 80:98 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 5 29 theme specific 822:829 arg1 trends 831:836 specific trends 822:836 specific trends 822:836 Although the profiles of each patient were unique, specific trends arose that correlated with the role of aberrant glycosylation in cancer progression. 36900350 8 30 theme N-linked 1442:1449 arg1 glycosylation 1451:1463 N-linked glycosylation 1442:1463 N-linked glycosylation 1442:1463 Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. 36900350 0 31 theme Lung 64:67 arg1 Cancer 69:74 Philippine Lung Cancer 53:74 Philippine Lung Cancer 53:74 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 0 32 theme Glycomic 0:7 arg1 Profiling 40:48 Glycomic, Glycoproteomic, and Proteomic Profiling 0:48 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 0:143 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 7 33 theme key 1212:1214 arg1 metabolism 1246:1255 metabolism 1246:1255 metabolism 1246:1255 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 7 33 theme key 1212:1214 arg1 adhesion 1263:1270 cell adhesion 1258:1270 cell adhesion 1258:1270 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 7 33 theme key 1212:1214 arg1 pathways 1288:1295 regulatory pathways 1277:1295 regulatory pathways 1277:1295 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 7 33 theme key 1212:1214 arg1 processes 1225:1233 key cellular processes 1212:1233 key cellular processes 1212:1233 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 0 34 theme Glycoproteomic 10:23 arg1 Profiling 40:48 Glycomic, Glycoproteomic, and Proteomic Profiling 0:48 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 0:143 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 5 35 theme patient 801:807 arg1 unique 814:819 unique 814:819 unique 814:819 Although the profiles of each patient were unique, specific trends arose that correlated with the role of aberrant glycosylation in cancer progression. 36900350 5 35 theme patient 801:807 arg1 profiles 784:791 the profiles 780:791 the profiles of each patient 780:807 Although the profiles of each patient were unique, specific trends arose that correlated with the role of aberrant glycosylation in cancer progression. 36900350 1 36 theme lung 263:266 arg1 cancers 268:274 lung cancers 263:274 lung cancers 263:274 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 7 37 gly glycosite 1099:1107 arg2 glycosite 1099:1107 glycosite 1099:1107 glycosite 1099:1107 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 0 38 dep Profiling 40:48 arg1 Study 113:117 Case Series Study 101:117 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 0:143 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 8 39 theme glycosylation 1489:1501 arg1 results 1503:1509 the protein glycosylation results 1477:1509 the protein glycosylation results 1477:1509 Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. 36900350 7 40 attach attached 1174:1181 arg1 glycoproteins 1186:1198 glycoproteins 1186:1198 glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways 1186:1295 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 7 40 attach attached 1174:1181 arg2 N-glycans 1146:1154 these sialofucosylated N-glycans 1123:1154 these sialofucosylated N-glycans 1123:1154 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 4 41 theme expression 706:715 arg1 stages 625:630 varying stages 617:630 varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1) 617:768 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 6 42 from increase 959:966 arg1 abundance 984:992 the relative abundance 971:992 the relative abundance of high-mannose 971:1008 Specifically, we observed a general increase in the relative abundance of high-mannose and sialofucosylated N-glycans in tumor samples. 36900350 4 43 dep panel 739:743 arg1 KRT19 753:757 KRT19 753:757 KRT19 753:757 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 4 43 dep panel 739:743 arg1 MUC1 764:767 MUC1 764:767 MUC1 764:767 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 4 43 dep panel 739:743 arg1 CD133 746:750 CD133 746:750 CD133 746:750 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 9 44 theme case 1524:1527 arg1 study 1536:1540 The present case series study 1512:1540 The present case series study 1512:1540 The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients. 36900350 7 45 gly sialofucosylated 1129:1144 arg1 N-glycans 1146:1154 these sialofucosylated N-glycans 1123:1154 these sialofucosylated N-glycans 1123:1154 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 8 46 theme significant 1333:1343 arg1 enrichment 1345:1354 significant enrichment 1333:1354 significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation 1333:1463 Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. 36900350 1 47 theme cell 208:211 arg1 NSCLC 229:233 NSCLC 229:233 NSCLC 229:233 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 1 47 theme cell 208:211 arg1 carcinoma 218:226 non-small cell lung carcinoma 198:226 non-small cell lung carcinoma (NSCLC) 198:234 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 8 48 link N-linked 1442:1449 arg1 glycosylation 1451:1463 N-linked glycosylation 1442:1463 N-linked glycosylation 1442:1463 Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. 36900350 5 49 gly glycosylation 886:898 arg1 cancer 903:908 cancer progression 903:920 cancer progression 903:920 Although the profiles of each patient were unique, specific trends arose that correlated with the role of aberrant glycosylation in cancer progression. 36900350 3 50 theme N-glycome 427:435 arg1 proteome 438:445 the N-glycome, proteome, and N-glycosylation distribution maps 423:484 proteome 438:445 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 1 51 theme carcinoma 218:226 arg1 cancer 150:155 Lung cancer 145:155 Lung cancer 145:155 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 1 51 theme carcinoma 218:226 arg1 cause 172:176 the leading cause 160:176 the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers 160:274 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 8 52 theme Protein 1298:1304 arg1 profiles 1317:1324 Protein expression profiles 1298:1324 Protein expression profiles 1298:1324 Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. 36900350 3 53 theme distribution 468:479 arg1 maps 481:484 the N-glycome, proteome, and N-glycosylation distribution maps 423:484 maps 481:484 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 9 54 theme mass-spectrometric 1595:1612 arg1 analysis 1614:1621 a multi-platform mass-spectrometric analysis 1578:1621 a multi-platform mass-spectrometric analysis 1578:1621 The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients. 36900350 4 55 with studies 604:610 arg1 stages 625:630 varying stages 617:630 varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1) 617:768 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 7 56 theme glycan 1075:1080 arg1 distribution 1082:1093 the glycan distribution 1071:1093 the glycan distribution per glycosite 1071:1107 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 9 57 theme Filipino 1640:1647 arg1 patients 1661:1668 Filipino lung cancer patients 1640:1668 Filipino lung cancer patients 1640:1668 The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients. 36900350 6 58 theme high-mannose 997:1008 arg1 abundance 984:992 the relative abundance 971:992 the relative abundance of high-mannose 971:1008 Specifically, we observed a general increase in the relative abundance of high-mannose and sialofucosylated N-glycans in tumor samples. 36900350 9 59 theme cancer 1654:1659 arg1 patients 1661:1668 Filipino lung cancer patients 1640:1668 Filipino lung cancer patients 1640:1668 The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients. 36900350 0 60 theme Patients 122:129 arg1 Study 113:117 Case Series Study 101:117 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 0:143 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 3 61 theme Filipino 522:529 arg1 patients 543:550 Filipino lung cancer patients 522:550 Filipino lung cancer patients (n = 5) 522:558 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 3 61 theme Filipino 522:529 arg1 n 553:553 n = 5 553:557 n = 5 553:557 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 1 62 theme cancer 181:186 arg1 death 188:192 cancer death 181:192 cancer death 181:192 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 8 63 theme proteins 1372:1379 arg1 enrichment 1345:1354 significant enrichment 1333:1354 significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation 1333:1463 Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. 36900350 6 64 gly sialofucosylated 1014:1029 arg1 N-glycans 1031:1039 N-glycans 1031:1039 N-glycans in tumor samples 1031:1056 Specifically, we observed a general increase in the relative abundance of high-mannose and sialofucosylated N-glycans in tumor samples. 36900350 3 65 theme tissues 511:517 arg1 maps 481:484 the N-glycome, proteome, and N-glycosylation distribution maps 423:484 maps 481:484 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 3 65 theme tissues 511:517 arg1 proteome 438:445 the N-glycome, proteome, and N-glycosylation distribution maps 423:484 proteome 438:445 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 4 66 theme varying 617:623 arg1 stages 625:630 varying stages 617:630 varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1) 617:768 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 5 67 theme glycosylation 886:898 arg1 role 869:872 the role 865:872 the role of aberrant glycosylation in cancer progression 865:920 Although the profiles of each patient were unique, specific trends arose that correlated with the role of aberrant glycosylation in cancer progression. 36900350 7 68 theme distribution 1082:1093 arg1 Analysis 1059:1066 Analysis 1059:1066 Analysis of the glycan distribution per glycosite 1059:1107 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 5 69 theme cancer 903:908 arg1 progression 910:920 cancer progression 903:920 cancer progression 903:920 Although the profiles of each patient were unique, specific trends arose that correlated with the role of aberrant glycosylation in cancer progression. 36900350 3 70 theme cancer 536:541 arg1 patients 543:550 Filipino lung cancer patients 522:550 Filipino lung cancer patients (n = 5) 522:558 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 3 70 theme cancer 536:541 arg1 n 553:553 n = 5 553:557 n = 5 553:557 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 0 71 dep Patients 122:129 arg1 Stages 131:136 Stages I-III 131:142 Patients Stages I-III 122:142 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 4 72 theme several 591:597 arg1 studies 604:610 several case studies 591:610 several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1) 591:768 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 0 73 theme Tissues 92:98 arg1 Profiling 40:48 Glycomic, Glycoproteomic, and Proteomic Profiling 0:48 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 0:143 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 2 74 gly glycoproteins 349:361 arg1 glycoproteins 349:361 glycoproteins 349:361 glycoproteins 349:361 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 6 75 from N-glycans 1031:1039 arg1 samples 1050:1056 tumor samples 1044:1056 tumor samples 1044:1056 Specifically, we observed a general increase in the relative abundance of high-mannose and sialofucosylated N-glycans in tumor samples. 36900350 0 76 theme Case 101:104 arg1 Study 113:117 Case Series Study 101:117 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 0:143 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 7 77 theme cellular 1216:1223 arg1 metabolism 1246:1255 metabolism 1246:1255 metabolism 1246:1255 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 7 77 theme cellular 1216:1223 arg1 adhesion 1263:1270 cell adhesion 1258:1270 cell adhesion 1258:1270 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 7 77 theme cellular 1216:1223 arg1 pathways 1288:1295 regulatory pathways 1277:1295 regulatory pathways 1277:1295 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 7 77 theme cellular 1216:1223 arg1 processes 1225:1233 key cellular processes 1212:1233 key cellular processes 1212:1233 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 4 78 theme status 672:677 arg1 stages 625:630 varying stages 617:630 varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1) 617:768 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 4 79 theme development 642:652 arg1 stages 625:630 varying stages 617:630 varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1) 617:768 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 8 80 theme protein 1481:1487 arg1 results 1503:1509 the protein glycosylation results 1477:1509 the protein glycosylation results 1477:1509 Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. 36900350 0 81 theme Proteomic 30:38 arg1 Profiling 40:48 Glycomic, Glycoproteomic, and Proteomic Profiling 0:48 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 0:143 Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III. 36900350 9 82 theme present 1516:1522 arg1 study 1536:1540 The present case series study 1512:1540 The present case series study 1512:1540 The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients. 36900350 3 83 theme = 555:555 arg1 patients 543:550 Filipino lung cancer patients 522:550 Filipino lung cancer patients (n = 5) 522:558 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 3 83 theme = 555:555 arg1 n 553:553 n = 5 553:557 n = 5 553:557 Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. 36900350 1 84 theme cancers 268:274 arg1 majority 251:258 majority 251:258 majority of lung cancers 251:274 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 9 85 theme series 1529:1534 arg1 study 1536:1540 The present case series study 1512:1540 The present case series study 1512:1540 The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients. 36900350 6 86 theme relative 975:982 arg1 abundance 984:992 the relative abundance 971:992 the relative abundance of high-mannose 971:1008 Specifically, we observed a general increase in the relative abundance of high-mannose and sialofucosylated N-glycans in tumor samples. 36900350 2 87 theme diagnostic 385:394 arg1 tools 396:400 diagnostic tools 385:400 diagnostic tools against NSCLC 385:414 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 2 87 theme diagnostic 385:394 arg1 glycans 337:343 glycans 337:343 glycans 337:343 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 2 87 theme diagnostic 385:394 arg1 glycoproteins 349:361 glycoproteins 349:361 glycoproteins 349:361 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 2 87 theme diagnostic 385:394 arg1 biomarkers 317:326 potential biomarkers 307:326 potential biomarkers 307:326 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 4 88 theme biomarker 696:704 arg1 expression 706:715 biomarker expression 696:715 biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1) 696:768 We present several case studies with varying stages of cancer development (I-III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). 36900350 7 89 theme sialofucosylated 1129:1144 arg1 N-glycans 1146:1154 these sialofucosylated N-glycans 1123:1154 these sialofucosylated N-glycans 1123:1154 Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. 36900350 8 90 theme expression 1306:1315 arg1 profiles 1317:1324 Protein expression profiles 1298:1324 Protein expression profiles 1298:1324 Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. 36900350 1 91 theme non-small 198:206 arg1 NSCLC 229:233 NSCLC 229:233 NSCLC 229:233 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 1 91 theme non-small 198:206 arg1 carcinoma 218:226 non-small cell lung carcinoma 198:226 non-small cell lung carcinoma (NSCLC) 198:234 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 9 92 theme first 1555:1559 arg1 demonstration 1561:1573 the first demonstration 1551:1573 the first demonstration of a multi-platform mass-spectrometric analysis 1551:1621 The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients. 36900350 6 93 theme general 951:957 arg1 increase 959:966 a general increase 949:966 a general increase in the relative abundance of high-mannose 949:1008 Specifically, we observed a general increase in the relative abundance of high-mannose and sialofucosylated N-glycans in tumor samples. 36900350 2 94 theme potential 307:315 arg1 tools 396:400 diagnostic tools 385:400 diagnostic tools against NSCLC 385:414 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 2 94 theme potential 307:315 arg1 glycans 337:343 glycans 337:343 glycans 337:343 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 2 94 theme potential 307:315 arg1 glycoproteins 349:361 glycoproteins 349:361 glycoproteins 349:361 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 2 94 theme potential 307:315 arg1 biomarkers 317:326 potential biomarkers 307:326 potential biomarkers 307:326 Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. 36900350 1 95 theme lung 213:216 arg1 NSCLC 229:233 NSCLC 229:233 NSCLC 229:233 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36900350 1 95 theme lung 213:216 arg1 carcinoma 218:226 non-small cell lung carcinoma 198:226 non-small cell lung carcinoma (NSCLC) 198:234 Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. 36592853 4 0 theme transmembrane 811:823 arg1 domain 825:830 a type II transmembrane domain 801:830 a type II transmembrane domain instead of a typical signal peptide 801:866 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 9 1 theme heterodimer 1905:1915 arg1 functions 1879:1887 the potential functions 1865:1887 the potential functions of Sc-GPA2/GPB5 heterodimer 1865:1915 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 9 1 theme heterodimer 1905:1915 arg1 neurohormone 1943:1954 an autocrine/paracrine neurohormone 1920:1954 an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults 1920:2030 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 6 2 gly glycosylation 1150:1162 arg2 residue 1204:1210 the conserved cysteine residue 1181:1210 the conserved cysteine residue (N78) of Sc-GPA2 1181:1227 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 6 2 gly glycosylation 1150:1162 arg2 Sc-GPA2 1221:1227 Sc-GPA2 1221:1227 Sc-GPA2 1221:1227 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 6 2 gly glycosylation 1150:1162 arg2 N78 1213:1215 N78 1213:1215 N78 1213:1215 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 10 3 theme chordate 2226:2233 arg1 lineage 2235:2241 the chordate lineage 2222:2241 the chordate lineage 2222:2241 Our study systematically investigated the GPA2/GPB5-GPHR system in ascidian for the first time, which offers insights into understanding the function and evolution of the GPH system within the chordate lineage. 36592853 3 4 theme GPH 507:509 arg1 Sc-GPA2 522:528 Sc-GPA2 522:528 Sc-GPA2 522:528 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 4 theme GPH 507:509 arg1 subunit 513:519 GPH α subunit 507:519 GPH α subunit (Sc-GPA2) 507:529 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 4 5 dep conserved 745:753 arg1 distinct 687:694 distinct 687:694 distinct 687:694 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 4 6 theme type 803:806 arg1 domain 825:830 a type II transmembrane domain 801:830 a type II transmembrane domain instead of a typical signal peptide 801:866 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 9 7 theme hybridization 1690:1702 arg1 results 1715:1721 in situ hybridization and RT-PCR results 1682:1721 in situ hybridization and RT-PCR results 1682:1721 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 0 8 attach present 56:62 arg2 receptor 47:54 its cognate receptor 35:54 its cognate receptor 35:54 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 0 8 attach present 56:62 arg1 ascidian 86:93 primitive chordate ascidian 67:93 primitive chordate ascidian 67:93 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 0 8 attach present 56:62 arg2 hormone 23:29 Ancestral glycoprotein hormone 0:29 Ancestral glycoprotein hormone 0:29 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 7 9 theme chordate 1359:1366 arg1 counterparts 1368:1379 its chordate counterparts 1355:1379 its chordate counterparts 1355:1379 Although Sc-GPB5 exhibited distinct topology and biochemical properties in contrast to its chordate counterparts, it could still interact with Sc-GPA2 to form a heterodimer. 36592853 10 10 theme GPH 2204:2206 arg1 system 2208:2213 the GPH system 2200:2213 the GPH system 2200:2213 Our study systematically investigated the GPA2/GPB5-GPHR system in ascidian for the first time, which offers insights into understanding the function and evolution of the GPH system within the chordate lineage. 36592853 0 11 theme functional 125:134 arg1 characterization 136:151 functional characterization 125:151 functional characterization 125:151 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 9 12 theme RT-PCR 1708:1713 arg1 results 1715:1721 in situ hybridization and RT-PCR results 1682:1721 in situ hybridization and RT-PCR results 1682:1721 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 6 13 theme cysteine 1195:1202 arg1 N78 1213:1215 N78 1213:1215 N78 1213:1215 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 6 13 theme cysteine 1195:1202 arg1 Sc-GPA2 1221:1227 Sc-GPA2 1221:1227 Sc-GPA2 1221:1227 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 6 13 theme cysteine 1195:1202 arg1 residue 1204:1210 the conserved cysteine residue 1181:1210 the conserved cysteine residue (N78) of Sc-GPA2 1181:1227 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 4 14 theme signal 853:858 arg1 peptide 860:866 a typical signal peptide 843:866 a type II transmembrane domain instead of a typical signal peptide 801:866 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 1 15 gly glycoprotein 158:169 arg1 glycoprotein 158:169 glycoprotein hormone 158:177 The glycoprotein hormone (GPH) system 154:190 The glycoprotein hormone (GPH) system is fundamentally significant in regulating the physiology of chordates, such as thyroid activity and gonadal function. 36592853 3 16 theme β 536:536 arg1 subunit 538:544 GPH β subunit 532:544 GPH β subunit (Sc-GPB5) 532:554 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 16 theme β 536:536 arg1 Sc-GPB5 547:553 Sc-GPB5 547:553 Sc-GPB5 547:553 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 8 17 from heterodimer 1514:1524 arg1 pathway 1541:1547 the Gs-cAMP pathway 1529:1547 the Gs-cAMP pathway 1529:1547 The Sc-GPHR was then confirmed to be activated by tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway, suggesting that Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway is evolutionarily conserved in chordates. 36592853 9 18 theme co-expression 1736:1748 arg1 patterns 1750:1757 the co-expression patterns 1732:1757 the co-expression patterns of Sc-GPA2 and Sc-GPB5 1732:1780 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 7 19 theme biochemical 1317:1327 arg1 properties 1329:1338 distinct topology and biochemical properties 1295:1338 distinct topology and biochemical properties 1295:1338 Although Sc-GPB5 exhibited distinct topology and biochemical properties in contrast to its chordate counterparts, it could still interact with Sc-GPA2 to form a heterodimer. 36592853 9 20 theme adults 2025:2030 arg1 functions 2012:2020 physiological functions 1998:2020 physiological functions of adults 1998:2030 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 9 20 theme adults 2025:2030 arg1 metamorphosis 1970:1982 metamorphosis 1970:1982 metamorphosis of larvae 1970:1992 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 7 21 theme topology 1304:1311 arg1 properties 1329:1338 distinct topology and biochemical properties 1295:1338 distinct topology and biochemical properties 1295:1338 Although Sc-GPB5 exhibited distinct topology and biochemical properties in contrast to its chordate counterparts, it could still interact with Sc-GPA2 to form a heterodimer. 36592853 7 22 dep counterparts 1368:1379 arg1 contrast 1343:1350 contrast 1343:1350 contrast 1343:1350 Although Sc-GPB5 exhibited distinct topology and biochemical properties in contrast to its chordate counterparts, it could still interact with Sc-GPA2 to form a heterodimer. 36592853 4 23 theme Comparative 642:652 arg1 analysis 664:671 Comparative structure analysis 642:671 Comparative structure analysis 642:671 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 0 24 theme chordate 77:84 arg1 ascidian 86:93 primitive chordate ascidian 67:93 primitive chordate ascidian 67:93 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 2 25 from knowledge 324:332 arg1 species 387:393 the primitive chordate ascidian species 355:393 the primitive chordate ascidian species 355:393 However, the knowledge of the GPH system in the primitive chordate ascidian species is largely lacking. 36592853 4 26 from subunits 718:725 arg1 distinct 687:694 distinct 687:694 distinct 687:694 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 9 27 dep in 1682:1683 arg1 situ 1685:1688 situ 1685:1688 situ 1685:1688 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 7 28 theme distinct 1295:1302 arg1 properties 1329:1338 distinct topology and biochemical properties 1295:1338 distinct topology and biochemical properties 1295:1338 Although Sc-GPB5 exhibited distinct topology and biochemical properties in contrast to its chordate counterparts, it could still interact with Sc-GPA2 to form a heterodimer. 36592853 9 29 theme in 1682:1683 arg1 hybridization 1690:1702 in situ hybridization 1682:1702 in situ hybridization 1682:1702 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 0 30 theme Ancestral 0:8 arg1 hormone 23:29 Ancestral glycoprotein hormone 0:29 Ancestral glycoprotein hormone 0:29 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 9 31 theme ascidian 1824:1831 arg1 larvae 1833:1838 ascidian larvae 1824:1838 ascidian larvae 1824:1838 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 8 32 theme Sc-GPA2/GPB5 1501:1512 arg1 heterodimer 1514:1524 tethered Sc-GPA2/GPB5 heterodimer 1492:1524 tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway 1492:1547 The Sc-GPHR was then confirmed to be activated by tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway, suggesting that Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway is evolutionarily conserved in chordates. 36592853 4 33 theme GPH 712:714 arg1 subunits 718:725 vertebrate GPH β subunits 701:725 vertebrate GPH β subunits 701:725 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 5 34 theme recombinant 902:912 arg1 Sc-GPA2 914:920 recombinant Sc-GPA2 902:920 recombinant Sc-GPA2 902:920 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 5 35 dep cells 1052:1056 arg1 out 1041:1043 out 1041:1043 out 1041:1043 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 3 36 theme repeat-containing 586:602 arg1 Sc-GPHR 632:638 Sc-GPHR 632:638 Sc-GPHR 632:638 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 36 theme repeat-containing 586:602 arg1 receptor 622:629 the cognate leucine-rich repeat-containing G protein-coupled receptor 561:629 the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR) 561:639 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 37 theme GPH 446:448 arg1 system 450:455 an ancestral GPH system 433:455 an ancestral GPH system 433:455 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 5 38 theme secretory 1071:1079 arg1 pathways 1081:1088 distinct secretory pathways 1062:1088 distinct secretory pathways 1062:1088 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 0 39 gly glycoprotein 10:21 arg1 glycoprotein 10:21 Ancestral glycoprotein hormone 0:29 Ancestral glycoprotein hormone 0:29 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 8 40 theme Gs-cAMP 1533:1539 arg1 pathway 1541:1547 the Gs-cAMP pathway 1529:1547 the Gs-cAMP pathway 1529:1547 The Sc-GPHR was then confirmed to be activated by tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway, suggesting that Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway is evolutionarily conserved in chordates. 36592853 3 41 theme cognate 565:571 arg1 Sc-GPHR 632:638 Sc-GPHR 632:638 Sc-GPHR 632:638 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 41 theme cognate 565:571 arg1 receptor 622:629 the cognate leucine-rich repeat-containing G protein-coupled receptor 561:629 the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR) 561:639 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 4 42 theme N-terminal 776:785 arg1 sequence 787:794 an atypical N-terminal sequence 764:794 an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide 764:866 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 3 43 from system 450:455 arg1 clava 481:485 the ascidian (Styela clava) 460:486 the ascidian (Styela clava) 460:486 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 44 theme Styela 474:479 arg1 clava 481:485 the ascidian (Styela clava) 460:486 the ascidian (Styela clava) 460:486 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 5 45 theme cells 979:983 arg1 lysates 942:948 cell lysates 937:948 cell lysates 937:948 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 5 45 theme cells 979:983 arg1 media 962:966 culture media 954:966 culture media 954:966 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 3 46 theme ascidian 464:471 arg1 clava 481:485 the ascidian (Styela clava) 460:486 the ascidian (Styela clava) 460:486 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 10 47 dep function 2174:2181 arg1 the 2170:2172 the 2170:2172 the 2170:2172 Our study systematically investigated the GPA2/GPB5-GPHR system in ascidian for the first time, which offers insights into understanding the function and evolution of the GPH system within the chordate lineage. 36592853 1 48 theme hormone 171:177 arg1 system 185:190 The glycoprotein hormone (GPH) system 154:190 The glycoprotein hormone (GPH) system 154:190 The glycoprotein hormone (GPH) system is fundamentally significant in regulating the physiology of chordates, such as thyroid activity and gonadal function. 36592853 1 48 theme hormone 171:177 arg1 significant 209:219 significant 209:219 significant 209:219 The glycoprotein hormone (GPH) system is fundamentally significant in regulating the physiology of chordates, such as thyroid activity and gonadal function. 36592853 3 49 theme protein-coupled 606:620 arg1 Sc-GPHR 632:638 Sc-GPHR 632:638 Sc-GPHR 632:638 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 49 theme protein-coupled 606:620 arg1 receptor 622:629 the cognate leucine-rich repeat-containing G protein-coupled receptor 561:629 the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR) 561:639 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 2 50 theme chordate 369:376 arg1 species 387:393 the primitive chordate ascidian species 355:393 the primitive chordate ascidian species 355:393 However, the knowledge of the GPH system in the primitive chordate ascidian species is largely lacking. 36592853 5 51 from presence 890:897 arg1 lysates 942:948 cell lysates 937:948 cell lysates 937:948 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 5 51 from presence 890:897 arg1 media 962:966 culture media 954:966 culture media 954:966 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 1 52 theme chordates 253:261 arg1 physiology 239:248 the physiology 235:248 the physiology of chordates, such as thyroid activity and gonadal function 235:308 The glycoprotein hormone (GPH) system is fundamentally significant in regulating the physiology of chordates, such as thyroid activity and gonadal function. 36592853 5 53 theme culture 954:960 arg1 media 962:966 culture media 954:966 culture media 954:966 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 9 54 theme Sc-GPA2/GPB5 1892:1903 arg1 heterodimer 1905:1915 Sc-GPA2/GPB5 heterodimer 1892:1915 Sc-GPA2/GPB5 heterodimer 1892:1915 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 8 55 theme heterodimer-initiated 1579:1599 arg1 pathway 1619:1625 Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway 1566:1625 Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway 1566:1625 The Sc-GPHR was then confirmed to be activated by tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway, suggesting that Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway is evolutionarily conserved in chordates. 36592853 4 56 theme II 808:809 arg1 domain 825:830 a type II transmembrane domain 801:830 a type II transmembrane domain instead of a typical signal peptide 801:866 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 8 57 theme signaling 1609:1617 arg1 pathway 1619:1625 Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway 1566:1625 Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway 1566:1625 The Sc-GPHR was then confirmed to be activated by tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway, suggesting that Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway is evolutionarily conserved in chordates. 36592853 6 58 theme Sc-GPA2 1221:1227 arg1 N78 1213:1215 N78 1213:1215 N78 1213:1215 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 6 58 theme Sc-GPA2 1221:1227 arg1 Sc-GPA2 1221:1227 Sc-GPA2 1221:1227 Sc-GPA2 1221:1227 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 6 58 theme Sc-GPA2 1221:1227 arg1 residue 1204:1210 the conserved cysteine residue 1181:1210 the conserved cysteine residue (N78) of Sc-GPA2 1181:1227 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 3 59 theme α 511:511 arg1 Sc-GPA2 522:528 Sc-GPA2 522:528 Sc-GPA2 522:528 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 59 theme α 511:511 arg1 subunit 513:519 GPH α subunit 507:519 GPH α subunit (Sc-GPA2) 507:529 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 1 60 theme thyroid 272:278 arg1 activity 280:287 thyroid activity 272:287 thyroid activity 272:287 The glycoprotein hormone (GPH) system is fundamentally significant in regulating the physiology of chordates, such as thyroid activity and gonadal function. 36592853 9 61 theme autocrine/paracrine 1923:1941 arg1 functions 1879:1887 the potential functions 1865:1887 the potential functions of Sc-GPA2/GPB5 heterodimer 1865:1915 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 9 61 theme autocrine/paracrine 1923:1941 arg1 neurohormone 1943:1954 an autocrine/paracrine neurohormone 1920:1954 an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults 1920:2030 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 2 62 theme system 345:350 arg1 knowledge 324:332 the knowledge 320:332 the knowledge of the GPH system in the primitive chordate ascidian species 320:393 However, the knowledge of the GPH system in the primitive chordate ascidian species is largely lacking. 36592853 6 63 gly non-glycosylated 1250:1265 arg1 Sc-GPB5 1238:1244 Sc-GPB5 1238:1244 Sc-GPB5 1238:1244 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 6 64 theme deglycosylation 1095:1109 arg1 experiments 1111:1121 The deglycosylation experiments 1091:1121 The deglycosylation experiments 1091:1121 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 10 65 theme system 2208:2213 arg1 evolution 2187:2195 evolution 2187:2195 evolution 2187:2195 Our study systematically investigated the GPA2/GPB5-GPHR system in ascidian for the first time, which offers insights into understanding the function and evolution of the GPH system within the chordate lineage. 36592853 10 65 theme system 2208:2213 arg1 function 2174:2181 function 2174:2181 function 2174:2181 Our study systematically investigated the GPA2/GPB5-GPHR system in ascidian for the first time, which offers insights into understanding the function and evolution of the GPH system within the chordate lineage. 36592853 9 66 theme larvae 1987:1992 arg1 functions 2012:2020 physiological functions 1998:2020 physiological functions of adults 1998:2030 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 9 66 theme larvae 1987:1992 arg1 metamorphosis 1970:1982 metamorphosis 1970:1982 metamorphosis of larvae 1970:1992 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 5 67 attach presence 890:897 arg2 Sc-GPB5 926:932 Sc-GPB5 926:932 Sc-GPB5 926:932 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 5 67 attach presence 890:897 arg2 Sc-GPA2 914:920 recombinant Sc-GPA2 902:920 recombinant Sc-GPA2 902:920 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 5 67 attach presence 890:897 arg1 media 962:966 culture media 954:966 culture media 954:966 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 5 67 attach presence 890:897 arg1 lysates 942:948 cell lysates 937:948 cell lysates 937:948 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 6 68 theme conserved 1185:1193 arg1 N78 1213:1215 N78 1213:1215 N78 1213:1215 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 6 68 theme conserved 1185:1193 arg1 Sc-GPA2 1221:1227 Sc-GPA2 1221:1227 Sc-GPA2 1221:1227 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 6 68 theme conserved 1185:1193 arg1 residue 1204:1210 the conserved cysteine residue 1181:1210 the conserved cysteine residue (N78) of Sc-GPA2 1181:1227 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 9 69 theme physiological 1998:2010 arg1 functions 2012:2020 physiological functions 1998:2020 physiological functions of adults 1998:2030 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 6 70 link N-linked 1141:1148 arg1 glycosylation 1150:1162 N-linked glycosylation 1141:1162 N-linked glycosylation 1141:1162 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 3 71 theme GPH 532:534 arg1 subunit 538:544 GPH β subunit 532:544 GPH β subunit (Sc-GPB5) 532:554 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 71 theme GPH 532:534 arg1 Sc-GPB5 547:553 Sc-GPB5 547:553 Sc-GPB5 547:553 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 4 72 theme structure 654:662 arg1 analysis 664:671 Comparative structure analysis 642:671 Comparative structure analysis 642:671 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 4 73 theme typical 845:851 arg1 peptide 860:866 a typical signal peptide 843:866 a type II transmembrane domain instead of a typical signal peptide 801:866 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 10 74 theme GPA2/GPB5-GPHR 2075:2088 arg1 system 2090:2095 the GPA2/GPB5-GPHR system 2071:2095 the GPA2/GPB5-GPHR system in ascidian for the first time, which offers insights into understanding the function and evolution of the GPH system within the chordate lineage 2071:2241 Our study systematically investigated the GPA2/GPB5-GPHR system in ascidian for the first time, which offers insights into understanding the function and evolution of the GPH system within the chordate lineage. 36592853 0 75 theme primitive 67:75 arg1 ascidian 86:93 primitive chordate ascidian 67:93 primitive chordate ascidian 67:93 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 1 76 theme glycoprotein 158:169 arg1 hormone 171:177 glycoprotein hormone 158:177 The glycoprotein hormone (GPH) system 154:190 The glycoprotein hormone (GPH) system is fundamentally significant in regulating the physiology of chordates, such as thyroid activity and gonadal function. 36592853 1 76 theme glycoprotein 158:169 arg1 GPH 180:182 GPH 180:182 GPH 180:182 The glycoprotein hormone (GPH) system is fundamentally significant in regulating the physiology of chordates, such as thyroid activity and gonadal function. 36592853 9 77 theme Sc-GPA2 1762:1768 arg1 patterns 1750:1757 the co-expression patterns 1732:1757 the co-expression patterns of Sc-GPA2 and Sc-GPB5 1732:1780 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 6 78 theme N-linked 1141:1148 arg1 glycosylation 1150:1162 N-linked glycosylation 1141:1162 N-linked glycosylation 1141:1162 The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. 36592853 9 79 theme Sc-GPB5 1774:1780 arg1 patterns 1750:1757 the co-expression patterns 1732:1757 the co-expression patterns of Sc-GPA2 and Sc-GPB5 1732:1780 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 0 80 theme Molecular 96:104 arg1 identification 106:119 Molecular identification 96:119 Molecular identification 96:119 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 5 81 theme distinct 1062:1069 arg1 pathways 1081:1088 distinct secretory pathways 1062:1088 distinct secretory pathways 1062:1088 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 5 82 theme Sc-GPA2 914:920 arg1 presence 890:897 the presence 886:897 the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells 886:983 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 4 83 with sequence 787:794 arg1 domain 825:830 a type II transmembrane domain 801:830 a type II transmembrane domain instead of a typical signal peptide 801:866 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 4 83 with sequence 787:794 arg1 peptide 860:866 a typical signal peptide 843:866 a type II transmembrane domain instead of a typical signal peptide 801:866 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 9 84 theme Sc-GPHR 1787:1793 arg1 transcripts 1795:1805 Sc-GPHR transcripts 1787:1805 Sc-GPHR transcripts 1787:1805 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 4 85 theme β 716:716 arg1 subunits 718:725 vertebrate GPH β subunits 701:725 vertebrate GPH β subunits 701:725 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 5 86 theme Sc-GPB5 926:932 arg1 presence 890:897 the presence 886:897 the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells 886:983 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 8 87 theme tethered 1492:1499 arg1 heterodimer 1514:1524 tethered Sc-GPA2/GPB5 heterodimer 1492:1524 tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway 1492:1547 The Sc-GPHR was then confirmed to be activated by tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway, suggesting that Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway is evolutionarily conserved in chordates. 36592853 3 88 theme ancestral 436:444 arg1 system 450:455 an ancestral GPH system 433:455 an ancestral GPH system 433:455 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 0 89 theme glycoprotein 10:21 arg1 hormone 23:29 Ancestral glycoprotein hormone 0:29 Ancestral glycoprotein hormone 0:29 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 2 90 theme ascidian 378:385 arg1 species 387:393 the primitive chordate ascidian species 355:393 the primitive chordate ascidian species 355:393 However, the knowledge of the GPH system in the primitive chordate ascidian species is largely lacking. 36592853 1 91 theme gonadal 293:299 arg1 function 301:308 gonadal function 293:308 gonadal function 293:308 The glycoprotein hormone (GPH) system is fundamentally significant in regulating the physiology of chordates, such as thyroid activity and gonadal function. 36592853 3 92 theme leucine-rich 573:584 arg1 Sc-GPHR 632:638 Sc-GPHR 632:638 Sc-GPHR 632:638 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 92 theme leucine-rich 573:584 arg1 receptor 622:629 the cognate leucine-rich repeat-containing G protein-coupled receptor 561:629 the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR) 561:639 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 4 93 theme vertebrate 701:710 arg1 subunits 718:725 vertebrate GPH β subunits 701:725 vertebrate GPH β subunits 701:725 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 0 94 theme cognate 39:45 arg1 receptor 47:54 its cognate receptor 35:54 its cognate receptor 35:54 Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization. 36592853 10 95 from system 2090:2095 arg1 ascidian 2100:2107 ascidian 2100:2107 ascidian 2100:2107 Our study systematically investigated the GPA2/GPB5-GPHR system in ascidian for the first time, which offers insights into understanding the function and evolution of the GPH system within the chordate lineage. 36592853 5 96 theme HEK293T 971:977 arg1 cells 979:983 HEK293T cells 971:983 HEK293T cells 971:983 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 4 97 theme atypical 767:774 arg1 sequence 787:794 an atypical N-terminal sequence 764:794 an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide 764:866 Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. 36592853 2 98 theme GPH 341:343 arg1 system 345:350 the GPH system 337:350 the GPH system 337:350 However, the knowledge of the GPH system in the primitive chordate ascidian species is largely lacking. 36592853 5 99 theme cell 937:940 arg1 lysates 942:948 cell lysates 937:948 cell lysates 937:948 By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. 36592853 9 100 theme potential 1869:1877 arg1 functions 1879:1887 the potential functions 1865:1887 the potential functions of Sc-GPA2/GPB5 heterodimer 1865:1915 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 9 100 theme potential 1869:1877 arg1 neurohormone 1943:1954 an autocrine/paracrine neurohormone 1920:1954 an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults 1920:2030 Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. 36592853 8 101 theme Sc-GPA2/GPB5 1566:1577 arg1 pathway 1619:1625 Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway 1566:1625 Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway 1566:1625 The Sc-GPHR was then confirmed to be activated by tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway, suggesting that Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway is evolutionarily conserved in chordates. 36592853 3 102 theme G 604:604 arg1 Sc-GPHR 632:638 Sc-GPHR 632:638 Sc-GPHR 632:638 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 3 102 theme G 604:604 arg1 receptor 622:629 the cognate leucine-rich repeat-containing G protein-coupled receptor 561:629 the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR) 561:639 Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). 36592853 10 103 theme first 2117:2121 arg1 time 2123:2126 the first time 2113:2126 the first time 2113:2126 Our study systematically investigated the GPA2/GPB5-GPHR system in ascidian for the first time, which offers insights into understanding the function and evolution of the GPH system within the chordate lineage. 36592853 8 104 theme Gs-cAMP 1601:1607 arg1 pathway 1619:1625 Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway 1566:1625 Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway 1566:1625 The Sc-GPHR was then confirmed to be activated by tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway, suggesting that Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway is evolutionarily conserved in chordates. 36592853 2 105 theme primitive 359:367 arg1 species 387:393 the primitive chordate ascidian species 355:393 the primitive chordate ascidian species 355:393 However, the knowledge of the GPH system in the primitive chordate ascidian species is largely lacking. 35934421 7 0 theme icELISA 1794:1800 arg1 method 1802:1807 an icELISA method 1791:1807 an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs 1791:1914 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 6 1 theme mAb 1450:1452 arg1 1A9 1454:1456 mAb 1A9 1450:1456 mAb 1A9 1450:1456 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 2 theme detection 1531:1539 arg1 limit 1522:1526 the limit 1518:1526 the limit of detection (LOD) of 0.21-43.72 μg L-1 1518:1566 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 7 3 theme molecules 1768:1776 arg1 antibodies 1748:1757 targeted broad-spectrum antibodies 1724:1757 targeted broad-spectrum antibodies of small molecules 1724:1776 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 1 4 from damage 287:292 arg1 humans 297:302 humans 297:302 humans 297:302 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 1 4 from damage 287:292 arg1 animals 308:314 animals 308:314 animals 308:314 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 4 5 theme mAb 1029:1031 arg1 1A9 1033:1035 mAb 1A9 1029:1035 mAb 1A9 1029:1035 Through molecular docking, it was found that mAb 1A9 and ester-type AAs showed a semi-enveloped structure through hydrogen bonds and hydrophobicity interaction. 35934421 6 6 from analysis 1597:1604 arg1 samples 1647:1653 various Aconitum L. samples 1627:1653 various Aconitum L. samples 1627:1653 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 5 7 dep structures 1265:1274 arg1 recognized 1282:1291 recognized 1282:1291 to be recognized of AAs 1276:1298 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 3 8 theme antibody 760:767 arg1 1A9 775:777 The monoclonal antibody (mAb) 1A9 745:777 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs 745:847 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 0 9 from modeling 124:131 arg1 immunoassay 156:166 immunoassay 156:166 immunoassay 156:166 Targeted preparation and recognition mechanism of broad-spectrum antibody specific to Aconitum alkaloids based on molecular modeling and its application in immunoassay. 35934421 7 10 theme broad-spectrum 1733:1746 arg1 antibodies 1748:1757 targeted broad-spectrum antibodies 1724:1757 targeted broad-spectrum antibodies of small molecules 1724:1776 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 6 11 theme ester-type 1498:1507 arg1 AAs 1509:1511 15 ester-type AAs 1495:1511 15 ester-type AAs 1495:1511 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 1 12 theme medicinal 215:223 arg1 ingredients 225:235 the main medicinal ingredients 206:235 the main medicinal ingredients of Aconitum L. herbs 206:256 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 1 12 theme medicinal 215:223 arg1 alkaloids 189:197 Ester-type Aconitum alkaloids 169:197 Ester-type Aconitum alkaloids (AAs) 169:203 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 6 13 theme Aconitum 1635:1642 arg1 samples 1647:1653 various Aconitum L. samples 1627:1653 various Aconitum L. samples 1627:1653 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 2 14 theme properties 678:687 arg1 similarity 601:610 the similarity 597:610 the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology 597:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 4 15 theme molecular 992:1000 arg1 docking 1002:1008 molecular docking 992:1008 molecular docking 992:1008 Through molecular docking, it was found that mAb 1A9 and ester-type AAs showed a semi-enveloped structure through hydrogen bonds and hydrophobicity interaction. 35934421 3 16 theme broad-spectrum 789:802 arg1 specificity 816:826 broad-spectrum recognition specificity 789:826 broad-spectrum recognition specificity of 15 ester-type AAs 789:847 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 6 17 theme developed 1366:1374 arg1 icELISA 1432:1438 icELISA 1432:1438 icELISA 1432:1438 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 17 theme developed 1366:1374 arg1 assay 1425:1429 The developed indirect competitive enzyme-linked immunosorbent assay 1362:1429 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 1362:1456 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 7 18 theme effective 1682:1690 arg1 strategy 1692:1699 an effective strategy 1679:1699 an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules 1679:1776 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 7 19 from detection 1861:1869 arg1 herbs 1910:1914 Aconitum L. herbs 1898:1914 Aconitum L. herbs 1898:1914 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 2 20 theme molecular 714:722 arg1 modeling 724:731 the computer-aided molecular modeling 695:731 the computer-aided molecular modeling technology 695:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 3 21 theme AAs 845:847 arg1 specificity 816:826 broad-spectrum recognition specificity 789:826 broad-spectrum recognition specificity of 15 ester-type AAs 789:847 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 0 22 theme Aconitum 86:93 arg1 alkaloids 95:103 Aconitum alkaloids 86:103 Aconitum alkaloids 86:103 Targeted preparation and recognition mechanism of broad-spectrum antibody specific to Aconitum alkaloids based on molecular modeling and its application in immunoassay. 35934421 5 23 theme acid 1155:1158 arg1 ARG107 1207:1212 ARG107 1207:1212 ARG107 1207:1212 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 5 23 theme acid 1155:1158 arg1 residues 1160:1167 The amino acid residues 1145:1167 The amino acid residues that responsible for recognition 1145:1200 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 6 24 theme AAs 1620:1622 arg1 analysis 1597:1604 the analysis 1593:1604 the analysis of ester-type AAs in various Aconitum L. samples 1593:1653 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 1 25 theme Aconitum 180:187 arg1 AAs 200:202 AAs 200:202 AAs 200:202 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 1 25 theme Aconitum 180:187 arg1 alkaloids 189:197 Ester-type Aconitum alkaloids 169:197 Ester-type Aconitum alkaloids (AAs) 169:203 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 1 25 theme Aconitum 180:187 arg1 ingredients 225:235 the main medicinal ingredients 206:235 the main medicinal ingredients of Aconitum L. herbs 206:256 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 3 26 theme high 872:875 arg1 sensitivity 877:887 a high sensitivity 870:887 a high sensitivity 870:887 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 2 27 theme 3-succinyl 496:505 arg1 ACO-HS 518:523 ACO-HS 518:523 ACO-HS 518:523 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 2 27 theme 3-succinyl 496:505 arg1 aconitine 507:515 3-succinyl aconitine 496:515 3-succinyl aconitine (ACO-HS) 496:524 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 2 27 theme 3-succinyl 496:505 arg1 hapten 553:558 an optimal hapten 542:558 an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology 542:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 2 28 theme stereo 615:620 arg1 structure 622:630 stereo structure 615:630 stereo structure 615:630 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 5 29 theme benzoyl 1319:1325 arg1 group 1327:1331 benzoyl group 1319:1331 benzoyl group 1319:1331 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 0 30 theme molecular 114:122 arg1 modeling 124:131 molecular modeling 114:131 molecular modeling 114:131 Targeted preparation and recognition mechanism of broad-spectrum antibody specific to Aconitum alkaloids based on molecular modeling and its application in immunoassay. 35934421 3 31 theme binding 898:904 arg1 concentration 940:952 half-maximum inhibition concentration 916:952 half-maximum inhibition concentration 916:952 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 3 31 theme binding 898:904 arg1 affinity 906:913 the binding affinity 894:913 the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1 894:981 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 2 32 theme AAs 491:493 arg1 method 470:475 an immunoassay method 455:475 an immunoassay method of ester-type AAs 455:493 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 0 33 theme Targeted 0:7 arg1 preparation 9:19 Targeted preparation 0:19 Targeted preparation 0:19 Targeted preparation and recognition mechanism of broad-spectrum antibody specific to Aconitum alkaloids based on molecular modeling and its application in immunoassay. 35934421 1 34 theme brain 271:275 arg1 damage 287:292 brain and heart damage 271:292 brain and heart damage in humans and animals 271:314 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 7 35 theme Aconitum 1898:1905 arg1 herbs 1910:1914 Aconitum L. herbs 1898:1914 Aconitum L. herbs 1898:1914 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 4 36 theme ester-type 1041:1050 arg1 AAs 1052:1054 ester-type AAs 1041:1054 ester-type AAs 1041:1054 Through molecular docking, it was found that mAb 1A9 and ester-type AAs showed a semi-enveloped structure through hydrogen bonds and hydrophobicity interaction. 35934421 2 37 theme distribution 644:655 arg1 similarity 601:610 the similarity 597:610 the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology 597:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 1 38 theme heart 281:285 arg1 damage 287:292 brain and heart damage 271:292 brain and heart damage in humans and animals 271:314 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 7 39 theme AAs 1891:1893 arg1 detection 1861:1869 rapid, sensitive, and high-throughput detection 1823:1869 rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs 1823:1914 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 3 40 theme inhibition 929:938 arg1 concentration 940:952 half-maximum inhibition concentration 916:952 half-maximum inhibition concentration 916:952 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 3 40 theme inhibition 929:938 arg1 affinity 906:913 the binding affinity 894:913 the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1 894:981 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 2 41 theme immunoassay 458:468 arg1 method 470:475 an immunoassay method 455:475 an immunoassay method of ester-type AAs 455:493 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 5 42 link N-linked 1338:1345 arg1 chains 1354:1359 N-linked carbon chains 1338:1359 N-linked carbon chains 1338:1359 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 6 43 theme immunosorbent 1411:1423 arg1 icELISA 1432:1438 icELISA 1432:1438 icELISA 1432:1438 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 43 theme immunosorbent 1411:1423 arg1 assay 1425:1429 The developed indirect competitive enzyme-linked immunosorbent assay 1362:1429 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 1362:1456 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 7 44 theme toxic 1874:1878 arg1 AAs 1891:1893 toxic ester-type AAs 1874:1893 toxic ester-type AAs 1874:1893 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 3 45 theme 0.73-130.36 μg L-1 964:981 arg1 concentration 940:952 half-maximum inhibition concentration 916:952 half-maximum inhibition concentration 916:952 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 3 45 theme 0.73-130.36 μg L-1 964:981 arg1 affinity 906:913 the binding affinity 894:913 the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1 894:981 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 0 46 theme specific 74:81 arg1 antibody 65:72 broad-spectrum antibody 50:72 broad-spectrum antibody specific to Aconitum alkaloids 50:103 Targeted preparation and recognition mechanism of broad-spectrum antibody specific to Aconitum alkaloids based on molecular modeling and its application in immunoassay. 35934421 0 47 theme broad-spectrum 50:63 arg1 antibody 65:72 broad-spectrum antibody 50:72 broad-spectrum antibody specific to Aconitum alkaloids 50:103 Targeted preparation and recognition mechanism of broad-spectrum antibody specific to Aconitum alkaloids based on molecular modeling and its application in immunoassay. 35934421 0 48 from application 141:151 arg1 immunoassay 156:166 immunoassay 156:166 immunoassay 156:166 Targeted preparation and recognition mechanism of broad-spectrum antibody specific to Aconitum alkaloids based on molecular modeling and its application in immunoassay. 35934421 5 49 theme N-linked 1338:1345 arg1 chains 1354:1359 N-linked carbon chains 1338:1359 N-linked carbon chains 1338:1359 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 1 50 theme Aconitum 240:247 arg1 herbs 252:256 Aconitum L. herbs 240:256 Aconitum L. herbs 240:256 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 6 51 theme enzyme-linked 1397:1409 arg1 icELISA 1432:1438 icELISA 1432:1438 icELISA 1432:1438 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 51 theme enzyme-linked 1397:1409 arg1 assay 1425:1429 The developed indirect competitive enzyme-linked immunosorbent assay 1362:1429 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 1362:1456 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 1 52 theme herbs 252:256 arg1 ingredients 225:235 the main medicinal ingredients 206:235 the main medicinal ingredients of Aconitum L. herbs 206:256 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 1 52 theme herbs 252:256 arg1 alkaloids 189:197 Ester-type Aconitum alkaloids 169:197 Ester-type Aconitum alkaloids (AAs) 169:203 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 2 53 theme designed 570:577 arg1 haptens 579:585 five designed haptens 565:585 five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology 565:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 4 54 theme semi-enveloped 1065:1078 arg1 structure 1080:1088 a semi-enveloped structure 1063:1088 a semi-enveloped structure through hydrogen bonds 1063:1111 Through molecular docking, it was found that mAb 1A9 and ester-type AAs showed a semi-enveloped structure through hydrogen bonds and hydrophobicity interaction. 35934421 7 55 theme small 1762:1766 arg1 molecules 1768:1776 small molecules 1762:1776 small molecules 1762:1776 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 6 56 theme competitive 1385:1395 arg1 icELISA 1432:1438 icELISA 1432:1438 icELISA 1432:1438 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 56 theme competitive 1385:1395 arg1 assay 1425:1429 The developed indirect competitive enzyme-linked immunosorbent assay 1362:1429 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 1362:1456 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 7 57 theme antibodies 1748:1757 arg1 preparation 1709:1719 the preparation 1705:1719 the preparation of targeted broad-spectrum antibodies of small molecules 1705:1776 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 6 58 from AAs 1620:1622 arg1 samples 1647:1653 various Aconitum L. samples 1627:1653 various Aconitum L. samples 1627:1653 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 7 59 theme targeted 1724:1731 arg1 antibodies 1748:1757 targeted broad-spectrum antibodies 1724:1757 targeted broad-spectrum antibodies of small molecules 1724:1776 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 4 60 theme hydrophobicity 1117:1130 arg1 interaction 1132:1142 hydrophobicity interaction 1117:1142 hydrophobicity interaction 1117:1142 Through molecular docking, it was found that mAb 1A9 and ester-type AAs showed a semi-enveloped structure through hydrogen bonds and hydrophobicity interaction. 35934421 6 61 theme AAs 1509:1511 arg1 determination 1478:1490 a sensitive determination 1466:1490 a sensitive determination of 15 ester-type AAs 1466:1511 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 3 62 theme monoclonal 749:758 arg1 antibody 760:767 monoclonal antibody 749:767 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs 745:847 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 3 62 theme monoclonal 749:758 arg1 mAb 770:772 mAb 770:772 mAb 770:772 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 1 63 theme main 210:213 arg1 ingredients 225:235 the main medicinal ingredients 206:235 the main medicinal ingredients of Aconitum L. herbs 206:256 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 1 63 theme main 210:213 arg1 alkaloids 189:197 Ester-type Aconitum alkaloids 169:197 Ester-type Aconitum alkaloids (AAs) 169:203 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 2 64 theme computer-aided 699:712 arg1 modeling 724:731 the computer-aided molecular modeling 695:731 the computer-aided molecular modeling technology 695:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 2 65 theme optimal 545:551 arg1 aconitine 507:515 3-succinyl aconitine 496:515 3-succinyl aconitine (ACO-HS) 496:524 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 2 65 theme optimal 545:551 arg1 hapten 553:558 an optimal hapten 542:558 an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology 542:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 6 66 theme L. 1644:1645 arg1 samples 1647:1653 various Aconitum L. samples 1627:1653 various Aconitum L. samples 1627:1653 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 67 theme 0.21-43.72 μg L-1 1550:1566 arg1 LOD 1542:1544 LOD 1542:1544 LOD 1542:1544 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 67 theme 0.21-43.72 μg L-1 1550:1566 arg1 detection 1531:1539 detection 1531:1539 detection (LOD) of 0.21-43.72 μg L-1 1531:1566 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 68 theme various 1627:1633 arg1 samples 1647:1653 various Aconitum L. samples 1627:1653 various Aconitum L. samples 1627:1653 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 69 link enzyme-linked 1397:1409 arg1 icELISA 1432:1438 icELISA 1432:1438 icELISA 1432:1438 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 69 link enzyme-linked 1397:1409 arg1 assay 1425:1429 The developed indirect competitive enzyme-linked immunosorbent assay 1362:1429 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 1362:1456 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 70 theme indirect 1376:1383 arg1 icELISA 1432:1438 icELISA 1432:1438 icELISA 1432:1438 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 6 70 theme indirect 1376:1383 arg1 assay 1425:1429 The developed indirect competitive enzyme-linked immunosorbent assay 1362:1429 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 1362:1456 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 3 71 dep concentration 940:952 arg1 IC50 955:958 IC50 955:958 IC50 955:958 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 2 72 theme ester-type 480:489 arg1 AAs 491:493 ester-type AAs 480:493 ester-type AAs 480:493 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 2 73 theme modeling 724:731 arg1 technology 733:742 the computer-aided molecular modeling technology 695:742 the computer-aided molecular modeling technology 695:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 3 74 theme recognition 804:814 arg1 specificity 816:826 broad-spectrum recognition specificity 789:826 broad-spectrum recognition specificity of 15 ester-type AAs 789:847 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 5 75 theme amino 1149:1153 arg1 ARG107 1207:1212 ARG107 1207:1212 ARG107 1207:1212 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 5 75 theme amino 1149:1153 arg1 residues 1160:1167 The amino acid residues 1145:1167 The amino acid residues that responsible for recognition 1145:1200 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 1 76 theme Ester-type 169:178 arg1 AAs 200:202 AAs 200:202 AAs 200:202 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 1 76 theme Ester-type 169:178 arg1 alkaloids 189:197 Ester-type Aconitum alkaloids 169:197 Ester-type Aconitum alkaloids (AAs) 169:203 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 1 76 theme Ester-type 169:178 arg1 ingredients 225:235 the main medicinal ingredients 206:235 the main medicinal ingredients of Aconitum L. herbs 206:256 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35934421 2 77 theme electronic 633:642 arg1 distribution 644:655 electronic distribution 633:655 electronic distribution 633:655 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 5 78 theme critical 1256:1263 arg1 group 1312:1316 acetyl group 1305:1316 acetyl group 1305:1316 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 5 78 theme critical 1256:1263 arg1 structures 1265:1274 the critical structures 1252:1274 the critical structures to be recognized of AAs 1252:1298 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 6 79 theme ester-type 1609:1618 arg1 AAs 1620:1622 ester-type AAs 1609:1622 ester-type AAs in various Aconitum L. samples 1609:1653 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 2 80 theme structure 622:630 arg1 similarity 601:610 the similarity 597:610 the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology 597:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 3 81 theme ester-type 834:843 arg1 AAs 845:847 15 ester-type AAs 831:847 15 ester-type AAs 831:847 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 7 82 theme L. 1907:1908 arg1 herbs 1910:1914 Aconitum L. herbs 1898:1914 Aconitum L. herbs 1898:1914 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 3 83 theme half-maximum 916:927 arg1 concentration 940:952 half-maximum inhibition concentration 916:952 half-maximum inhibition concentration 916:952 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 3 83 theme half-maximum 916:927 arg1 affinity 906:913 the binding affinity 894:913 the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1 894:981 The monoclonal antibody (mAb) 1A9 exhibited broad-spectrum recognition specificity of 15 ester-type AAs was obtained and had a high sensitivity with the binding affinity (half-maximum inhibition concentration, IC50) of 0.73-130.36 μg L-1. 35934421 2 84 theme physicochemical 662:676 arg1 properties 678:687 physicochemical properties 662:687 physicochemical properties using the computer-aided molecular modeling technology 662:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 2 85 theme broad-spectrum 417:430 arg1 antibody 432:439 a high-performance and broad-spectrum antibody 394:439 antibody 432:439 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 2 86 theme present 359:365 arg1 study 367:371 the present study 355:371 the present study 355:371 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 0 87 theme recognition 25:35 arg1 mechanism 37:45 recognition mechanism 25:45 recognition mechanism 25:45 Targeted preparation and recognition mechanism of broad-spectrum antibody specific to Aconitum alkaloids based on molecular modeling and its application in immunoassay. 35934421 7 88 theme ester-type 1880:1889 arg1 AAs 1891:1893 toxic ester-type AAs 1874:1893 toxic ester-type AAs 1874:1893 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 2 89 theme high-performance 396:411 arg1 antibody 432:439 a high-performance and broad-spectrum antibody 394:439 antibody 432:439 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 2 90 from haptens 579:585 arg1 aconitine 507:515 3-succinyl aconitine 496:515 3-succinyl aconitine (ACO-HS) 496:524 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 2 90 from haptens 579:585 arg1 hapten 553:558 an optimal hapten 542:558 an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology 542:742 In the present study, we aimed to produce a high-performance and broad-spectrum antibody and establish an immunoassay method of ester-type AAs, 3-succinyl aconitine (ACO-HS) was selected as an optimal hapten from five designed haptens comparing the similarity of stereo structure, electronic distribution, and physicochemical properties using the computer-aided molecular modeling technology. 35934421 5 91 theme acetyl 1305:1310 arg1 group 1312:1316 acetyl group 1305:1316 acetyl group 1305:1316 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 5 91 theme acetyl 1305:1310 arg1 structures 1265:1274 the critical structures 1252:1274 the critical structures to be recognized of AAs 1252:1298 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 0 92 theme antibody 65:72 arg1 preparation 9:19 Targeted preparation 0:19 Targeted preparation 0:19 Targeted preparation and recognition mechanism of broad-spectrum antibody specific to Aconitum alkaloids based on molecular modeling and its application in immunoassay. 35934421 0 92 theme antibody 65:72 arg1 mechanism 37:45 recognition mechanism 25:45 recognition mechanism 25:45 Targeted preparation and recognition mechanism of broad-spectrum antibody specific to Aconitum alkaloids based on molecular modeling and its application in immunoassay. 35934421 7 93 theme high-throughput 1845:1859 arg1 detection 1861:1869 rapid, sensitive, and high-throughput detection 1823:1869 rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs 1823:1914 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 7 94 theme sensitive 1830:1838 arg1 detection 1861:1869 rapid, sensitive, and high-throughput detection 1823:1869 rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs 1823:1914 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 6 95 from samples 1647:1653 arg1 analysis 1597:1604 the analysis 1593:1604 the analysis of ester-type AAs in various Aconitum L. samples 1593:1653 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 7 96 theme rapid 1823:1827 arg1 detection 1861:1869 rapid, sensitive, and high-throughput detection 1823:1869 rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs 1823:1914 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 6 97 theme sensitive 1468:1476 arg1 determination 1478:1490 a sensitive determination 1466:1490 a sensitive determination of 15 ester-type AAs 1466:1511 The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) based on mAb 1A9 allowed a sensitive determination of 15 ester-type AAs with the limit of detection (LOD) of 0.21-43.72 μg L-1, and it was suitable for the analysis of ester-type AAs in various Aconitum L. samples. 35934421 7 98 theme available 1809:1817 arg1 method 1802:1807 an icELISA method 1791:1807 an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs 1791:1914 These results provided an effective strategy for the preparation of targeted broad-spectrum antibodies of small molecules and proposed an icELISA method available for rapid, sensitive, and high-throughput detection of toxic ester-type AAs in Aconitum L. herbs. 35934421 4 99 theme hydrogen 1098:1105 arg1 bonds 1107:1111 hydrogen bonds 1098:1111 hydrogen bonds 1098:1111 Through molecular docking, it was found that mAb 1A9 and ester-type AAs showed a semi-enveloped structure through hydrogen bonds and hydrophobicity interaction. 35934421 5 100 theme carbon 1347:1352 arg1 chains 1354:1359 N-linked carbon chains 1338:1359 N-linked carbon chains 1338:1359 The amino acid residues that responsible for recognition were ARG107, GLU55, PRO113, VAL36, and SER64, and the critical structures to be recognized of AAs were acetyl group, benzoyl group, and N-linked carbon chains. 35934421 1 101 theme L. 249:250 arg1 herbs 252:256 Aconitum L. herbs 240:256 Aconitum L. herbs 240:256 Ester-type Aconitum alkaloids (AAs), the main medicinal ingredients of Aconitum L. herbs, could cause brain and heart damage in humans and animals and have raised concerns worldwide. 35197973 4 0 theme novel 818:822 arg1 method 824:829 this novel method 813:829 this novel method 813:829 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 6 1 theme 90 1585:1586 arg1 % 1587:1587 % 1587:1587 % 1587:1587 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 3 2 theme imaging 650:656 arg1 spectrometry 663:674 MALDI imaging mass spectrometry 644:674 MALDI imaging mass spectrometry (IMS) 644:680 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 3 2 theme imaging 650:656 arg1 IMS 677:679 IMS 677:679 IMS 677:679 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 1 3 theme array 227:231 arg1 assay 175:179 the GlycoTyper assay 160:179 the GlycoTyper assay which is a streamlined antibody capture slide array approach 160:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 3 theme array 227:231 arg1 approach 233:240 a streamlined antibody capture slide array approach 190:240 a streamlined antibody capture slide array approach 190:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 5 4 dep stage 1146:1150 arg1 patients 1277:1284 37 patients 1274:1284 37 patients with METAVIR stage 4 fibrosis (cirrhosis) 1274:1326 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 4 dep stage 1146:1150 arg1 stage 1196:1200 10 METAVIR stage 1 and 18 METAVIR stage 2 1162:1202 stage 1196:1200 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 4 dep stage 1146:1150 arg1 fibrosis 1219:1226 fibrosis 1219:1226 fibrosis 1219:1226 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 4 dep stage 1146:1150 arg1 stage 1173:1177 10 METAVIR stage 1 and 18 METAVIR stage 2 1162:1202 stage 1173:1177 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 4 dep stage 1146:1150 arg1 patients 1231:1238 6 patients 1229:1238 6 patients with METAVIR stage 3 fibrosis 1229:1268 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 4 dep stage 1146:1150 arg1 fibrosis 1152:1159 fibrosis 1152:1159 early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) 1140:1203 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 5 theme METAVIR 1245:1251 arg1 fibrosis 1261:1268 METAVIR stage 3 fibrosis 1245:1268 METAVIR stage 3 fibrosis 1245:1268 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 6 6 theme Several 1330:1336 arg1 alterations 1344:1354 Several major alterations 1330:1354 Several major alterations in glycosylation 1330:1371 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 4 7 theme IgG 869:871 arg1 glycosylation 846:858 the glycosylation 842:858 the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis 842:1014 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 0 8 theme Biomarker 88:96 arg1 Signature 98:106 a Biomarker Signature 86:106 a Biomarker Signature of Liver Fibrosis 86:124 GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. 35197973 3 9 theme captured 531:538 arg1 glycoproteins 540:552 antibody captured glycoproteins 522:552 antibody captured glycoproteins 522:552 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 3 10 gly glycoproteins 540:552 arg1 glycoproteins 540:552 antibody captured glycoproteins 522:552 antibody captured glycoproteins 522:552 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 6 11 theme early 1479:1483 arg1 fibrosis 1485:1492 early fibrosis 1479:1492 early fibrosis (sensitivity of 84% with 90% specificity) 1479:1534 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 4 12 theme liver 1001:1005 arg1 fibrosis 1007:1014 biopsy confirmed liver fibrosis 984:1014 biopsy confirmed liver fibrosis 984:1014 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 3 13 theme N-glycosidase 579:591 arg1 F 593:593 peptide N-glycosidase F 571:593 peptide N-glycosidase F (PNGase F) 571:604 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 3 13 theme N-glycosidase 579:591 arg1 F 603:603 PNGase F 596:603 PNGase F 596:603 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 5 14 dep disease 1110:1116 arg1 fibrosis 1129:1136 fibrosis 1129:1136 fibrosis 1129:1136 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 0 15 theme Fibrosis 117:124 arg1 Signature 98:106 a Biomarker Signature 86:106 a Biomarker Signature of Liver Fibrosis 86:124 GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. 35197973 4 16 dep confirmed 991:999 arg1 biopsy 984:989 biopsy 984:989 biopsy 984:989 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 4 17 used utilized 804:811 arg2 we 801:802 we 801:802 we 801:802 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 5 18 theme fibrosis 1074:1081 arg1 evidence 1062:1069 no evidence 1059:1069 no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)) 1059:1327 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 0 19 theme IgG 59:61 arg1 Analysis 47:54 the Glycan Analysis 36:54 the Glycan Analysis of IgG 36:61 GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. 35197973 4 20 with patients 970:977 arg1 fibrosis 1007:1014 biopsy confirmed liver fibrosis 984:1014 biopsy confirmed liver fibrosis 984:1014 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 6 21 theme % 1450:1450 arg1 sensitivity 1433:1443 sensitivity 1433:1443 sensitivity of 92% 1433:1450 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 6 21 theme % 1450:1450 arg1 specificity 1458:1468 a specificity 1456:1468 a specificity of 90% 1456:1475 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 6 22 theme of 1507:1508 arg1 % 1512:1512 sensitivity of 84% 1495:1512 sensitivity of 84% with 90% specificity 1495:1533 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 2 23 theme processing 414:423 arg1 protocol 425:432 a simplified processing protocol 401:432 a simplified processing protocol that requires no purification or sugar modifications prior to analysis 401:503 This method needs only a few microliters of serum and utilizes a simplified processing protocol that requires no purification or sugar modifications prior to analysis. 35197973 5 24 theme METAVIR 1291:1297 arg1 fibrosis 1307:1314 METAVIR stage 4 fibrosis 1291:1314 METAVIR stage 4 fibrosis (cirrhosis) 1291:1326 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 24 theme METAVIR 1291:1297 arg1 cirrhosis 1317:1325 cirrhosis 1317:1325 cirrhosis 1317:1325 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 6 25 theme sensitivity 1561:1571 arg1 % 1578:1578 sensitivity of 94% 1561:1578 sensitivity of 94% with 90% specificity 1561:1599 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 5 26 theme METAVIR 1165:1171 arg1 stage 1173:1177 10 METAVIR stage 1 and 18 METAVIR stage 2 1162:1202 stage 1173:1177 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 27 with patients 1231:1238 arg1 fibrosis 1261:1268 METAVIR stage 3 fibrosis 1245:1268 METAVIR stage 3 fibrosis 1245:1268 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 27 with patients 1231:1238 arg1 cirrhosis 1317:1325 cirrhosis 1317:1325 cirrhosis 1317:1325 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 27 with patients 1231:1238 arg1 fibrosis 1307:1314 METAVIR stage 4 fibrosis 1291:1314 METAVIR stage 4 fibrosis (cirrhosis) 1291:1326 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 1 28 theme captured 275:282 arg1 glycoproteins 290:302 captured serum glycoproteins 275:302 captured serum glycoproteins including immunoglobulin G (IgG) 275:335 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 28 theme captured 275:282 arg1 G 329:329 immunoglobulin G 314:329 immunoglobulin G (IgG) 314:335 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 29 theme glycoproteins 290:302 arg1 N-glycans 262:270 N-glycans 262:270 N-glycans of captured serum glycoproteins including immunoglobulin G (IgG) 262:335 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 6 30 theme % 1521:1521 arg1 specificity 1523:1533 90% specificity 1519:1533 90% specificity 1519:1533 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 3 31 theme MALDI 644:648 arg1 spectrometry 663:674 MALDI imaging mass spectrometry 644:674 MALDI imaging mass spectrometry (IMS) 644:680 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 3 31 theme MALDI 644:648 arg1 IMS 677:679 IMS 677:679 IMS 677:679 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 6 32 with % 1578:1578 arg1 specificity 1589:1599 90% specificity 1585:1599 90% specificity 1585:1599 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 5 33 with patients 1087:1094 arg1 disease 1110:1116 no liver disease 1101:1116 no liver disease 1101:1116 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 33 with patients 1087:1094 arg1 stage 1121:1125 stage 0 1121:1127 stage 0 1121:1127 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 34 theme liver 1104:1108 arg1 disease 1110:1116 no liver disease 1101:1116 no liver disease 1101:1116 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 4 35 theme patient 756:762 arg1 cohorts 764:770 large patient cohorts 750:770 large patient cohorts with fibrosis and cirrhosis 750:798 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 1 36 theme antibody 204:211 arg1 assay 175:179 the GlycoTyper assay 160:179 the GlycoTyper assay which is a streamlined antibody capture slide array approach 160:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 36 theme antibody 204:211 arg1 approach 233:240 a streamlined antibody capture slide array approach 190:240 a streamlined antibody capture slide array approach 190:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 0 37 dep GlycoFibroTyper 0:14 arg1 Development 71:81 the Development 67:81 the Development of a Biomarker Signature of Liver Fibrosis 67:124 GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. 35197973 0 37 dep GlycoFibroTyper 0:14 arg1 Method 25:30 A Novel Method 17:30 A Novel Method for the Glycan Analysis of IgG 17:61 GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. 35197973 4 38 link N-linked 701:708 arg1 glycans 710:716 N-linked glycans 701:716 N-linked glycans 701:716 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 6 39 theme % 1587:1587 arg1 specificity 1589:1599 90% specificity 1585:1599 90% specificity 1585:1599 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 5 40 theme late 1208:1211 arg1 fibrosis 1074:1081 fibrosis 1074:1081 fibrosis (41 patients with no liver disease or stage 0 fibrosis) 1074:1137 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 40 theme late 1208:1211 arg1 stage 1213:1217 late stage 1208:1217 late stage 1208:1217 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 1 41 theme slide 221:225 arg1 assay 175:179 the GlycoTyper assay 160:179 the GlycoTyper assay which is a streamlined antibody capture slide array approach 160:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 41 theme slide 221:225 arg1 approach 233:240 a streamlined antibody capture slide array approach 190:240 a streamlined antibody capture slide array approach 190:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 6 42 theme 90 1519:1520 arg1 % 1521:1521 % 1521:1521 % 1521:1521 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 3 43 theme mass 658:661 arg1 spectrometry 663:674 MALDI imaging mass spectrometry 644:674 MALDI imaging mass spectrometry (IMS) 644:680 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 3 43 theme mass 658:661 arg1 IMS 677:679 IMS 677:679 IMS 677:679 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 2 44 theme purification 451:462 arg1 modifications 473:485 no purification or sugar modifications 448:485 modifications 473:485 This method needs only a few microliters of serum and utilizes a simplified processing protocol that requires no purification or sugar modifications prior to analysis. 35197973 6 45 theme major 1338:1342 arg1 alterations 1344:1354 Several major alterations 1330:1354 Several major alterations in glycosylation 1330:1371 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 4 46 theme confirmed 991:999 arg1 fibrosis 1007:1014 biopsy confirmed liver fibrosis 984:1014 biopsy confirmed liver fibrosis 984:1014 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 0 47 theme Signature 98:106 arg1 Development 71:81 the Development 67:81 the Development of a Biomarker Signature of Liver Fibrosis 67:124 GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. 35197973 0 47 theme Signature 98:106 arg1 Method 25:30 A Novel Method 17:30 A Novel Method for the Glycan Analysis of IgG 17:61 GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. 35197973 5 48 theme stage 1253:1257 arg1 fibrosis 1261:1268 METAVIR stage 3 fibrosis 1245:1268 METAVIR stage 3 fibrosis 1245:1268 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 3 49 theme antibody 522:529 arg1 glycoproteins 540:552 antibody captured glycoproteins 522:552 antibody captured glycoproteins 522:552 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 1 50 theme GlycoTyper 164:173 arg1 assay 175:179 the GlycoTyper assay 160:179 the GlycoTyper assay which is a streamlined antibody capture slide array approach 160:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 50 theme GlycoTyper 164:173 arg1 approach 233:240 a streamlined antibody capture slide array approach 190:240 a streamlined antibody capture slide array approach 190:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 4 51 theme total 863:867 arg1 IgG 869:871 total IgG 863:871 total IgG 863:871 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 0 52 theme Liver 111:115 arg1 Fibrosis 117:124 Liver Fibrosis 111:124 Liver Fibrosis 111:124 GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. 35197973 3 53 theme peptide 571:577 arg1 F 593:593 peptide N-glycosidase F 571:593 peptide N-glycosidase F (PNGase F) 571:604 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 3 53 theme peptide 571:577 arg1 F 603:603 PNGase F 596:603 PNGase F 596:603 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 6 54 dep fibrosis 1485:1492 arg1 % 1512:1512 sensitivity of 84% 1495:1512 sensitivity of 84% with 90% specificity 1495:1533 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 6 55 theme % 1475:1475 arg1 sensitivity 1433:1443 sensitivity 1433:1443 sensitivity of 92% 1433:1450 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 6 55 theme % 1475:1475 arg1 specificity 1458:1468 a specificity 1456:1468 a specificity of 90% 1456:1475 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 6 56 with % 1512:1512 arg1 specificity 1523:1533 90% specificity 1519:1533 90% specificity 1519:1533 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 5 57 theme early 1140:1144 arg1 stage 1146:1150 early stage 1140:1150 early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) 1140:1203 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 57 theme early 1140:1144 arg1 fibrosis 1074:1081 fibrosis 1074:1081 fibrosis (41 patients with no liver disease or stage 0 fibrosis) 1074:1137 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 4 58 from glycosylation 846:858 arg1 cohort 956:961 a cohort 954:961 a cohort of 106 patients with biopsy confirmed liver fibrosis 954:1014 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 3 59 theme PNGase 596:601 arg1 F 593:593 peptide N-glycosidase F 571:593 peptide N-glycosidase F (PNGase F) 571:604 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 3 59 theme PNGase 596:601 arg1 F 603:603 PNGase F 596:603 PNGase F 596:603 In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). 35197973 4 60 from cohorts 764:770 arg1 IgG 741:743 IgG 741:743 IgG from large patient cohorts with fibrosis and cirrhosis 741:798 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 5 61 with patients 1277:1284 arg1 fibrosis 1261:1268 METAVIR stage 3 fibrosis 1245:1268 METAVIR stage 3 fibrosis 1245:1268 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 61 with patients 1277:1284 arg1 cirrhosis 1317:1325 cirrhosis 1317:1325 cirrhosis 1317:1325 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 61 with patients 1277:1284 arg1 fibrosis 1307:1314 METAVIR stage 4 fibrosis 1291:1314 METAVIR stage 4 fibrosis (cirrhosis) 1291:1326 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 2 62 theme sugar 467:471 arg1 modifications 473:485 no purification or sugar modifications 448:485 modifications 473:485 This method needs only a few microliters of serum and utilizes a simplified processing protocol that requires no purification or sugar modifications prior to analysis. 35197973 5 63 dep fibrosis 1074:1081 arg1 patients 1087:1094 41 patients 1084:1094 41 patients with no liver disease or stage 0 fibrosis 1084:1136 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 4 64 with cohorts 764:770 arg1 cirrhosis 790:798 cirrhosis 790:798 cirrhosis 790:798 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 4 64 with cohorts 764:770 arg1 fibrosis 777:784 fibrosis 777:784 fibrosis 777:784 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 1 65 gly glycoproteins 290:302 arg1 glycoproteins 290:302 captured serum glycoproteins 275:302 captured serum glycoproteins including immunoglobulin G (IgG) 275:335 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 65 gly glycoproteins 290:302 arg1 G 329:329 immunoglobulin G 314:329 immunoglobulin G (IgG) 314:335 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 4 66 gly glycosylation 846:858 arg1 IgG1 885:888 IgG1 885:888 IgG1 885:888 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 4 66 gly glycosylation 846:858 arg1 IgG 869:871 total IgG 863:871 total IgG 863:871 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 4 66 gly glycosylation 846:858 arg1 IgG4 906:909 IgG4 906:909 IgG4 906:909 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 4 66 gly glycosylation 846:858 arg1 cohort 956:961 a cohort 954:961 a cohort of 106 patients with biopsy confirmed liver fibrosis 954:1014 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 4 66 gly glycosylation 846:858 arg1 IgG3 897:900 IgG3 897:900 IgG3 897:900 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 4 67 theme IgG3 897:900 arg1 glycosylation 846:858 the glycosylation 842:858 the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis 842:1014 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 6 68 from alterations 1344:1354 arg1 glycosylation 1359:1371 glycosylation 1359:1371 glycosylation 1359:1371 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 1 69 theme immunoglobulin 314:327 arg1 IgG 332:334 IgG 332:334 IgG 332:334 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 69 theme immunoglobulin 314:327 arg1 G 329:329 immunoglobulin G 314:329 immunoglobulin G (IgG) 314:335 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 6 70 dep fibrosis 1423:1430 arg1 sensitivity 1433:1443 sensitivity 1433:1443 sensitivity of 92% 1433:1450 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 6 70 dep fibrosis 1423:1430 arg1 specificity 1458:1468 a specificity 1456:1468 a specificity of 90% 1456:1475 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 4 71 theme IgG1 885:888 arg1 glycosylation 846:858 the glycosylation 842:858 the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis 842:1014 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 6 72 theme sensitivity 1495:1505 arg1 % 1512:1512 sensitivity of 84% 1495:1512 sensitivity of 84% with 90% specificity 1495:1533 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 5 73 theme METAVIR 1188:1194 arg1 stage 1196:1200 10 METAVIR stage 1 and 18 METAVIR stage 2 1162:1202 stage 1196:1200 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 2 74 theme simplified 403:412 arg1 protocol 425:432 a simplified processing protocol 401:432 a simplified processing protocol that requires no purification or sugar modifications prior to analysis 401:503 This method needs only a few microliters of serum and utilizes a simplified processing protocol that requires no purification or sugar modifications prior to analysis. 35197973 6 75 theme of 1573:1574 arg1 % 1578:1578 sensitivity of 94% 1561:1578 sensitivity of 94% with 90% specificity 1561:1599 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 5 76 theme stage 1299:1303 arg1 fibrosis 1307:1314 METAVIR stage 4 fibrosis 1291:1314 METAVIR stage 4 fibrosis (cirrhosis) 1291:1326 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 5 76 theme stage 1299:1303 arg1 cirrhosis 1317:1325 cirrhosis 1317:1325 cirrhosis 1317:1325 Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). 35197973 0 77 theme Novel 19:23 arg1 Method 25:30 A Novel Method 17:30 A Novel Method for the Glycan Analysis of IgG 17:61 GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. 35197973 4 78 from alterations 686:696 arg1 glycans 710:716 N-linked glycans 701:716 N-linked glycans 701:716 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 4 79 theme N-linked 701:708 arg1 glycans 710:716 N-linked glycans 701:716 N-linked glycans 701:716 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 2 80 theme serum 382:386 arg1 microliters 367:377 only a few microliters 356:377 only a few microliters of serum 356:386 This method needs only a few microliters of serum and utilizes a simplified processing protocol that requires no purification or sugar modifications prior to analysis. 35197973 4 81 theme IgG4 906:909 arg1 glycosylation 846:858 the glycosylation 842:858 the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis 842:1014 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 6 82 theme significant 1539:1549 arg1 fibrosis 1551:1558 significant fibrosis 1539:1558 significant fibrosis (sensitivity of 94% with 90% specificity) 1539:1600 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 0 83 theme Glycan 40:45 arg1 Analysis 47:54 the Glycan Analysis 36:54 the Glycan Analysis of IgG 36:61 GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. 35197973 1 84 theme serum 284:288 arg1 glycoproteins 290:302 captured serum glycoproteins 275:302 captured serum glycoproteins including immunoglobulin G (IgG) 275:335 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 84 theme serum 284:288 arg1 G 329:329 immunoglobulin G 314:329 immunoglobulin G (IgG) 314:335 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 6 85 dep fibrosis 1551:1558 arg1 % 1578:1578 sensitivity of 94% 1561:1578 sensitivity of 94% with 90% specificity 1561:1599 Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity). 35197973 1 86 theme streamlined 192:202 arg1 assay 175:179 the GlycoTyper assay 160:179 the GlycoTyper assay which is a streamlined antibody capture slide array approach 160:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 86 theme streamlined 192:202 arg1 approach 233:240 a streamlined antibody capture slide array approach 190:240 a streamlined antibody capture slide array approach 190:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 4 87 theme patients 970:977 arg1 cohort 956:961 a cohort 954:961 a cohort of 106 patients with biopsy confirmed liver fibrosis 954:1014 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 4 88 theme large 750:754 arg1 cohorts 764:770 large patient cohorts 750:770 large patient cohorts with fibrosis and cirrhosis 750:798 As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. 35197973 1 89 theme capture 213:219 arg1 assay 175:179 the GlycoTyper assay 160:179 the GlycoTyper assay which is a streamlined antibody capture slide array approach 160:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 35197973 1 89 theme capture 213:219 arg1 approach 233:240 a streamlined antibody capture slide array approach 190:240 a streamlined antibody capture slide array approach 190:240 Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). 37001434 4 0 theme blood 587:591 arg1 repertoires 605:615 paired human BM plasma cell and peripheral blood (PB) B-cell repertoires 544:615 paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- 544:672 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 11 1 from expression 1903:1912 arg1 cells 1935:1939 long-lived plasma cells 1917:1939 long-lived plasma cells 1917:1939 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 6 2 theme PB 1188:1189 arg1 cells 1200:1204 PB memory B cells 1188:1204 PB memory B cells 1188:1204 For three patients, we identified clonotypes shared between BM plasma cells and PB memory B cells. 37001434 8 3 theme ACPA-producing 1372:1385 arg1 cells 1397:1401 ACPA-producing BM plasma cells 1372:1401 ACPA-producing BM plasma cells 1372:1401 ACPA-producing BM plasma cells were identified in two ACPA+ patients. 37001434 11 4 theme single-cell 1694:1704 arg1 investigation 1706:1718 single-cell investigation 1694:1718 single-cell investigation of B-cell repertoires in RA bone marrow 1694:1758 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 4 5 theme RA 648:649 arg1 patients 651:658 four ACPA+ RA patients 637:658 four ACPA+ RA patients 637:658 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 2 6 theme plasma 249:254 arg1 cells 256:260 Long-lived BM plasma cells 235:260 Long-lived BM plasma cells 235:260 Long-lived BM plasma cells constitute our humoral immune memory and are essential for infection-specific immunity. 37001434 5 7 theme heavy-light 852:862 arg1 chains 864:869 >900 paired heavy-light chains 840:869 >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) 840:1015 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 9 8 from cells 1524:1528 arg1 antibodies 1489:1498 44 recombinantly expressed monoclonal antibodies 1451:1498 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells 1451:1528 Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. 37001434 6 9 theme BM 1168:1169 arg1 cells 1178:1182 BM plasma cells 1168:1182 BM plasma cells 1168:1182 For three patients, we identified clonotypes shared between BM plasma cells and PB memory B cells. 37001434 1 10 theme plasma 188:193 arg1 cells 195:199 plasma cells 188:199 plasma cells residing in the bone marrow (BM) 188:232 A majority of circulating IgG is produced by plasma cells residing in the bone marrow (BM). 37001434 0 11 theme producing 126:134 arg1 cells 136:140 anti-citrulline autoantibody producing cells 97:140 anti-citrulline autoantibody producing cells 97:140 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 2 12 theme humoral 277:283 arg1 memory 292:297 our humoral immune memory 273:297 our humoral immune memory 273:297 Long-lived BM plasma cells constitute our humoral immune memory and are essential for infection-specific immunity. 37001434 9 13 theme antibodies 1489:1498 arg1 antibodies 1489:1498 44 recombinantly expressed monoclonal antibodies 1451:1498 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells 1451:1528 Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. 37001434 9 13 theme antibodies 1489:1498 arg1 Three 1442:1446 Three 1442:1446 Three 1442:1446 Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. 37001434 9 14 theme ACPA+ 1505:1509 arg1 cells 1524:1528 ACPA+ RA BM plasma cells 1505:1528 ACPA+ RA BM plasma cells 1505:1528 Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. 37001434 4 15 theme single-cell 694:704 arg1 approaches 706:715 two different single-cell approaches 680:715 two different single-cell approaches 680:715 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 9 16 theme BM 1514:1515 arg1 cells 1524:1528 ACPA+ RA BM plasma cells 1505:1528 ACPA+ RA BM plasma cells 1505:1528 Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. 37001434 7 17 theme clonal 1352:1357 arg1 convergence 1359:1369 clonal convergence 1352:1369 clonal convergence 1352:1369 Notably, four individuals displayed plasma cells with identical heavy chains but different light chains, which may indicate receptor revision or clonal convergence. 37001434 5 18 theme IgG/A 1045:1049 arg1 repertoires 1051:1061 IgG/A repertoires 1045:1061 IgG/A repertoires 1045:1061 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 2 19 theme Long-lived 235:244 arg1 cells 256:260 Long-lived BM plasma cells 235:260 Long-lived BM plasma cells 235:260 Long-lived BM plasma cells constitute our humoral immune memory and are essential for infection-specific immunity. 37001434 5 20 theme CD138 921:925 arg1 expression 927:936 surface CD138 expression 913:936 surface CD138 expression 913:936 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 5 21 theme surface 913:919 arg1 expression 927:936 surface CD138 expression 913:936 surface CD138 expression 913:936 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 6 22 theme B 1198:1198 arg1 cells 1200:1204 PB memory B cells 1188:1204 PB memory B cells 1188:1204 For three patients, we identified clonotypes shared between BM plasma cells and PB memory B cells. 37001434 11 23 theme new 1769:1771 arg1 understanding 1773:1785 new understanding 1769:1785 new understanding of human plasma cells clonal relationships 1769:1828 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 4 24 from repertoires 605:615 arg1 patients 651:658 four ACPA+ RA patients 637:658 four ACPA+ RA patients 637:658 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 4 24 from repertoires 605:615 arg1 RA 633:634 seropositive RA 620:634 seropositive RA 620:634 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 4 24 from repertoires 605:615 arg1 ACPA- 668:672 one ACPA- 664:672 one ACPA- 664:672 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 5 25 theme plasma 879:884 arg1 cells 886:890 BM plasma cells 876:890 BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) 876:1015 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 11 26 from marrow 1753:1758 arg1 investigation 1706:1718 single-cell investigation 1694:1718 single-cell investigation of B-cell repertoires in RA bone marrow 1694:1758 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 11 27 theme clonal 1809:1814 arg1 relationships 1816:1828 human plasma cells clonal relationships 1790:1828 human plasma cells clonal relationships 1790:1828 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 4 28 dep investigated 531:542 arg1 followed 763:770 followed 763:770 followed by recombinant antibody generation 763:805 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 5 29 from cells 886:890 arg1 chains 864:869 >900 paired heavy-light chains 840:869 >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) 840:1015 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 5 29 from cells 886:890 arg1 analysis 828:835 Immunoglobulin (Ig) analysis 808:835 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) 808:1015 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 1 30 theme IgG 169:171 arg1 majority 145:152 A majority 143:152 A majority of circulating IgG 143:171 A majority of circulating IgG is produced by plasma cells residing in the bone marrow (BM). 37001434 11 31 theme plasma 1796:1801 arg1 relationships 1816:1828 human plasma cells clonal relationships 1790:1828 human plasma cells clonal relationships 1790:1828 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 11 32 from repertoires 1730:1740 arg1 marrow 1753:1758 RA bone marrow 1745:1758 RA bone marrow 1745:1758 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 0 33 from compartment 34:44 arg1 arthritis 60:68 rheumatoid arthritis 49:68 rheumatoid arthritis 49:68 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 3 34 theme rheumatoid 436:445 arg1 RA 458:459 RA 458:459 RA 458:459 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 3 34 theme rheumatoid 436:445 arg1 arthritis 447:455 rheumatoid arthritis 436:455 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA) 436:520 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 0 35 theme anti-citrulline 97:111 arg1 cells 136:140 anti-citrulline autoantibody producing cells 97:140 anti-citrulline autoantibody producing cells 97:140 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 0 36 dep relationships 79:91 arg1 compartment 34:44 The human bone marrow plasma cell compartment 0:44 The human bone marrow plasma cell compartment in rheumatoid arthritis 0:68 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 7 37 theme receptor 1331:1338 arg1 revision 1340:1347 receptor revision 1331:1347 receptor revision 1331:1347 Notably, four individuals displayed plasma cells with identical heavy chains but different light chains, which may indicate receptor revision or clonal convergence. 37001434 11 38 theme long-lived 1917:1926 arg1 cells 1935:1939 long-lived plasma cells 1917:1939 long-lived plasma cells 1917:1939 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 4 39 theme cytometry 723:731 arg1 sorting 733:739 flow cytometry sorting 718:739 flow cytometry sorting 718:739 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 5 40 theme Immunoglobulin 808:821 arg1 analysis 828:835 Immunoglobulin (Ig) analysis 808:835 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) 808:1015 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 4 41 theme BM 557:558 arg1 cell 567:570 paired human BM plasma cell 544:570 paired human BM plasma cell 544:570 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 8 42 theme plasma 1390:1395 arg1 cells 1397:1401 ACPA-producing BM plasma cells 1372:1401 ACPA-producing BM plasma cells 1372:1401 ACPA-producing BM plasma cells were identified in two ACPA+ patients. 37001434 0 43 theme bone 10:13 arg1 marrow 15:20 human bone marrow 4:20 The human bone marrow plasma cell compartment in rheumatoid arthritis 0:68 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 3 44 theme pathogenic 399:408 arg1 autoantibodies 500:513 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies 436:513 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA) 436:520 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 3 44 theme pathogenic 399:408 arg1 autoantibodies 410:423 potentially pathogenic autoantibodies 387:423 potentially pathogenic autoantibodies 387:423 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 4 45 theme cell 567:570 arg1 repertoires 605:615 paired human BM plasma cell and peripheral blood (PB) B-cell repertoires 544:615 paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- 544:672 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 0 46 theme plasma 22:27 arg1 compartment 34:44 The human bone marrow plasma cell compartment 0:44 The human bone marrow plasma cell compartment in rheumatoid arthritis 0:68 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 5 47 theme XBP1 1011:1014 arg1 expression 980:989 gene expression 975:989 gene expression of MZB1, JCHAIN and XBP1 975:1014 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 7 48 theme light 1298:1302 arg1 chains 1304:1309 different light chains 1288:1309 different light chains 1288:1309 Notably, four individuals displayed plasma cells with identical heavy chains but different light chains, which may indicate receptor revision or clonal convergence. 37001434 0 49 theme rheumatoid 49:58 arg1 arthritis 60:68 rheumatoid arthritis 49:68 rheumatoid arthritis 49:68 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 2 50 theme infection-specific 321:338 arg1 immunity 340:347 infection-specific immunity 321:347 infection-specific immunity 321:347 Long-lived BM plasma cells constitute our humoral immune memory and are essential for infection-specific immunity. 37001434 4 51 theme paired 544:549 arg1 cell 567:570 paired human BM plasma cell 544:570 paired human BM plasma cell 544:570 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 4 52 theme recombinant 775:785 arg1 generation 796:805 recombinant antibody generation 775:805 recombinant antibody generation 775:805 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 3 53 theme anti-citrullinated 473:490 arg1 autoantibodies 500:513 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies 436:513 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA) 436:520 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 3 53 theme anti-citrullinated 473:490 arg1 ACPA 516:519 ACPA 516:519 ACPA 516:519 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 1 54 theme bone 217:220 arg1 BM 230:231 BM 230:231 BM 230:231 A majority of circulating IgG is produced by plasma cells residing in the bone marrow (BM). 37001434 1 54 theme bone 217:220 arg1 marrow 222:227 the bone marrow 213:227 the bone marrow (BM) 213:232 A majority of circulating IgG is produced by plasma cells residing in the bone marrow (BM). 37001434 5 55 theme MZB1 994:997 arg1 expression 980:989 gene expression 975:989 gene expression of MZB1, JCHAIN and XBP1 975:1014 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 7 56 theme heavy 1271:1275 arg1 chains 1277:1282 identical heavy chains 1261:1282 identical heavy chains 1261:1282 Notably, four individuals displayed plasma cells with identical heavy chains but different light chains, which may indicate receptor revision or clonal convergence. 37001434 11 57 theme bone 1748:1751 arg1 marrow 1753:1758 RA bone marrow 1745:1758 RA bone marrow 1745:1758 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 5 58 theme JCHAIN 1000:1005 arg1 expression 980:989 gene expression 975:989 gene expression of MZB1, JCHAIN and XBP1 975:1014 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 11 59 theme B-cell 1723:1728 arg1 repertoires 1730:1740 B-cell repertoires 1723:1740 B-cell repertoires in RA bone marrow 1723:1758 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 5 60 from differences 1030:1040 arg1 repertoires 1051:1061 IgG/A repertoires 1045:1061 IgG/A repertoires 1045:1061 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 5 60 from differences 1030:1040 arg1 glycosylation 1076:1088 N-linked glycosylation 1067:1088 N-linked glycosylation 1067:1088 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 7 61 theme plasma 1243:1248 arg1 cells 1250:1254 plasma cells 1243:1254 plasma cells 1243:1254 Notably, four individuals displayed plasma cells with identical heavy chains but different light chains, which may indicate receptor revision or clonal convergence. 37001434 4 62 theme peripheral 576:585 arg1 PB 594:595 PB 594:595 PB 594:595 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 4 62 theme peripheral 576:585 arg1 blood 587:591 peripheral blood 576:591 peripheral blood (PB) 576:596 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 11 63 theme plasma 1928:1933 arg1 cells 1935:1939 long-lived plasma cells 1917:1939 long-lived plasma cells 1917:1939 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 5 64 theme paired 845:850 arg1 chains 864:869 >900 paired heavy-light chains 840:869 >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) 840:1015 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 6 65 theme plasma 1171:1176 arg1 cells 1178:1182 BM plasma cells 1168:1182 BM plasma cells 1168:1182 For three patients, we identified clonotypes shared between BM plasma cells and PB memory B cells. 37001434 4 66 theme ACPA+ 642:646 arg1 patients 651:658 four ACPA+ RA patients 637:658 four ACPA+ RA patients 637:658 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 5 67 theme chains 864:869 arg1 analysis 828:835 Immunoglobulin (Ig) analysis 808:835 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) 808:1015 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 11 68 theme relevant 1862:1869 arg1 expression 1903:1912 pathogenically relevant disease-associated autoantibody expression 1847:1912 pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells 1847:1939 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 2 69 theme immune 285:290 arg1 memory 292:297 our humoral immune memory 273:297 our humoral immune memory 273:297 Long-lived BM plasma cells constitute our humoral immune memory and are essential for infection-specific immunity. 37001434 9 70 theme monoclonal 1478:1487 arg1 antibodies 1489:1498 44 recombinantly expressed monoclonal antibodies 1451:1498 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells 1451:1528 Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. 37001434 4 71 theme seropositive 620:631 arg1 RA 633:634 seropositive RA 620:634 seropositive RA 620:634 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 5 72 theme N-linked 1067:1074 arg1 glycosylation 1076:1088 N-linked glycosylation 1067:1088 N-linked glycosylation 1067:1088 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 9 73 theme expressed 1468:1476 arg1 antibodies 1489:1498 44 recombinantly expressed monoclonal antibodies 1451:1498 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells 1451:1528 Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. 37001434 10 74 theme citrullinated 1628:1640 arg1 histone-4 1642:1650 citrullinated histone-4 1628:1650 citrullinated histone-4 1628:1650 Out of these, two clones reacted with citrullinated histone-4 and activated neutrophils. 37001434 9 75 theme RA 1511:1512 arg1 cells 1524:1528 ACPA+ RA BM plasma cells 1505:1528 ACPA+ RA BM plasma cells 1505:1528 Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. 37001434 4 76 theme different 684:692 arg1 approaches 706:715 two different single-cell approaches 680:715 two different single-cell approaches 680:715 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 11 77 theme autoantibody 1890:1901 arg1 expression 1903:1912 pathogenically relevant disease-associated autoantibody expression 1847:1912 pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells 1847:1939 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 2 78 theme BM 246:247 arg1 cells 256:260 Long-lived BM plasma cells 235:260 Long-lived BM plasma cells 235:260 Long-lived BM plasma cells constitute our humoral immune memory and are essential for infection-specific immunity. 37001434 5 79 from analysis 828:835 arg1 cells 886:890 BM plasma cells 876:890 BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) 876:1015 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 9 80 theme plasma 1517:1522 arg1 cells 1524:1528 ACPA+ RA BM plasma cells 1505:1528 ACPA+ RA BM plasma cells 1505:1528 Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. 37001434 11 81 theme human 1790:1794 arg1 relationships 1816:1828 human plasma cells clonal relationships 1790:1828 human plasma cells clonal relationships 1790:1828 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 5 82 theme BM 876:877 arg1 cells 886:890 BM plasma cells 876:890 BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) 876:1015 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 6 83 theme memory 1191:1196 arg1 cells 1200:1204 PB memory B cells 1188:1204 PB memory B cells 1188:1204 For three patients, we identified clonotypes shared between BM plasma cells and PB memory B cells. 37001434 5 84 dep profiles 955:962 arg1 including 965:973 including 965:973 including gene expression of MZB1, JCHAIN and XBP1 965:1014 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 0 85 theme Clonal 72:77 arg1 relationships 79:91 Clonal relationships 72:91 Clonal relationships 72:91 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 1 86 theme circulating 157:167 arg1 IgG 169:171 circulating IgG 157:171 circulating IgG 157:171 A majority of circulating IgG is produced by plasma cells residing in the bone marrow (BM). 37001434 11 87 theme relationships 1816:1828 arg1 understanding 1773:1785 new understanding 1769:1785 new understanding of human plasma cells clonal relationships 1769:1828 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 11 88 dep relevant 1862:1869 arg1 disease-associated 1871:1888 disease-associated 1871:1888 disease-associated 1871:1888 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 5 89 link N-linked 1067:1074 arg1 glycosylation 1076:1088 N-linked glycosylation 1067:1088 N-linked glycosylation 1067:1088 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 11 90 theme cells 1803:1807 arg1 relationships 1816:1828 human plasma cells clonal relationships 1790:1828 human plasma cells clonal relationships 1790:1828 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 0 91 theme autoantibody 113:124 arg1 cells 136:140 anti-citrulline autoantibody producing cells 97:140 anti-citrulline autoantibody producing cells 97:140 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 5 92 theme gene 975:978 arg1 expression 980:989 gene expression 975:989 gene expression of MZB1, JCHAIN and XBP1 975:1014 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 3 93 theme arthritis 447:455 arg1 autoantibodies 500:513 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies 436:513 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA) 436:520 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 3 93 theme arthritis 447:455 arg1 ACPA 516:519 ACPA 516:519 ACPA 516:519 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 0 94 theme human 4:8 arg1 marrow 15:20 human bone marrow 4:20 The human bone marrow plasma cell compartment in rheumatoid arthritis 0:68 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 4 95 theme plasma 560:565 arg1 cell 567:570 paired human BM plasma cell 544:570 paired human BM plasma cell 544:570 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 4 96 theme flow 718:721 arg1 sorting 733:739 flow cytometry sorting 718:739 flow cytometry sorting 718:739 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 10 97 theme activated 1656:1664 arg1 neutrophils 1666:1676 activated neutrophils 1656:1676 activated neutrophils 1656:1676 Out of these, two clones reacted with citrullinated histone-4 and activated neutrophils. 37001434 0 98 theme marrow 15:20 arg1 compartment 34:44 The human bone marrow plasma cell compartment 0:44 The human bone marrow plasma cell compartment in rheumatoid arthritis 0:68 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 5 99 theme transcriptome 941:953 arg1 profiles 955:962 transcriptome profiles 941:962 transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) 941:1015 Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. 37001434 11 100 from investigation 1706:1718 arg1 marrow 1753:1758 RA bone marrow 1745:1758 RA bone marrow 1745:1758 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 9 101 theme citrullinated 1566:1578 arg1 peptides 1580:1587 citrullinated peptides 1566:1587 citrullinated peptides 1566:1587 Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. 37001434 11 102 theme repertoires 1730:1740 arg1 investigation 1706:1718 single-cell investigation 1694:1718 single-cell investigation of B-cell repertoires in RA bone marrow 1694:1758 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 8 103 theme BM 1387:1388 arg1 cells 1397:1401 ACPA-producing BM plasma cells 1372:1401 ACPA-producing BM plasma cells 1372:1401 ACPA-producing BM plasma cells were identified in two ACPA+ patients. 37001434 3 104 theme -associated 461:471 arg1 autoantibodies 500:513 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies 436:513 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA) 436:520 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 3 104 theme -associated 461:471 arg1 ACPA 516:519 ACPA 516:519 ACPA 516:519 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 0 105 theme cell 29:32 arg1 compartment 34:44 The human bone marrow plasma cell compartment 0:44 The human bone marrow plasma cell compartment in rheumatoid arthritis 0:68 The human bone marrow plasma cell compartment in rheumatoid arthritis - Clonal relationships and anti-citrulline autoantibody producing cells. 37001434 7 106 theme different 1288:1296 arg1 chains 1304:1309 different light chains 1288:1309 different light chains 1288:1309 Notably, four individuals displayed plasma cells with identical heavy chains but different light chains, which may indicate receptor revision or clonal convergence. 37001434 3 107 theme autoantibodies 410:423 arg1 reservoir 374:382 a reservoir 372:382 a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA) 372:520 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 4 108 theme human 551:555 arg1 cell 567:570 paired human BM plasma cell 544:570 paired human BM plasma cell 544:570 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 7 109 theme identical 1261:1269 arg1 chains 1277:1282 identical heavy chains 1261:1282 identical heavy chains 1261:1282 Notably, four individuals displayed plasma cells with identical heavy chains but different light chains, which may indicate receptor revision or clonal convergence. 37001434 4 110 theme B-cell 598:603 arg1 repertoires 605:615 paired human BM plasma cell and peripheral blood (PB) B-cell repertoires 544:615 paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- 544:672 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 37001434 11 111 theme RA 1745:1746 arg1 marrow 1753:1758 RA bone marrow 1745:1758 RA bone marrow 1745:1758 In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells. 37001434 3 112 theme protein 492:498 arg1 autoantibodies 500:513 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies 436:513 rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA) 436:520 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 3 112 theme protein 492:498 arg1 ACPA 516:519 ACPA 516:519 ACPA 516:519 They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). 37001434 4 113 theme antibody 787:794 arg1 generation 796:805 recombinant antibody generation 775:805 recombinant antibody generation 775:805 Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. 35385697 0 0 theme tuft 96:99 arg1 hyperplasia 106:116 tuft cell hyperplasia 96:116 tuft cell hyperplasia 96:116 Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. 35385697 6 1 theme genes 958:962 arg1 expression 931:940 the expression 927:940 the expression of Gsdmc family genes 927:962 Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. 35385697 1 2 theme integral 156:163 arg1 epithelium 139:148 The epithelium 135:148 The epithelium 135:148 The epithelium is an integral component of mucosal barrier and host immunity. 35385697 1 2 theme integral 156:163 arg1 component 165:173 an integral component 153:173 an integral component of mucosal barrier and host immunity 153:210 The epithelium is an integral component of mucosal barrier and host immunity. 35385697 6 3 theme family 951:956 arg1 genes 958:962 Gsdmc family genes 945:962 Gsdmc family genes 945:962 Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. 35385697 9 4 theme inflammation-associated 1260:1282 arg1 diseases 1290:1297 type 2 inflammation-associated human diseases 1253:1297 type 2 inflammation-associated human diseases 1253:1297 Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases. 35385697 3 5 theme resulting 478:486 arg1 milieu 497:502 the resulting cytokine milieu 474:502 the resulting cytokine milieu 474:502 However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. 35385697 5 6 theme transcription 730:742 arg1 factor 744:749 the transcription factor 726:749 the transcription factor STAT6 726:755 By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. 35385697 6 7 theme Gsdmc 945:949 arg1 genes 958:962 Gsdmc family genes 945:962 Gsdmc family genes 945:962 Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. 35385697 8 8 theme effective 1103:1111 arg1 immunity 1127:1134 effective anti-helminth immunity 1103:1134 effective anti-helminth immunity 1103:1134 GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. 35385697 9 9 theme human 1284:1288 arg1 diseases 1290:1297 type 2 inflammation-associated human diseases 1253:1297 type 2 inflammation-associated human diseases 1253:1297 Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases. 35385697 0 10 theme cell 101:104 arg1 hyperplasia 106:116 tuft cell hyperplasia 96:116 tuft cell hyperplasia 96:116 Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. 35385697 9 11 theme diseases 1290:1297 arg1 treatment 1240:1248 future treatment 1233:1248 future treatment of type 2 inflammation-associated human diseases 1233:1297 Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases. 35385697 2 12 theme " 291:291 arg1 cytokines 293:301 "alarmin" cytokines 283:301 "alarmin" cytokines 283:301 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 2 12 theme " 291:291 arg1 IL-33 339:343 IL-33 339:343 IL-33 339:343 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 2 12 theme " 291:291 arg1 interleukin-25 312:325 interleukin-25 312:325 interleukin-25 312:325 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 0 13 theme Gasdermin 122:130 arg1 C 132:132 Gasdermin C 122:132 Gasdermin C 122:132 Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. 35385697 5 14 theme IL-25 866:870 arg1 production 872:881 IL-25 production 866:881 IL-25 production 866:881 By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. 35385697 2 15 theme helminth 390:397 arg1 expulsion 399:407 helminth expulsion 390:407 helminth expulsion 390:407 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 2 16 theme alarmin 284:290 arg1 cytokines 293:301 "alarmin" cytokines 283:301 "alarmin" cytokines 283:301 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 2 16 theme alarmin 284:290 arg1 IL-33 339:343 IL-33 339:343 IL-33 339:343 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 2 16 theme alarmin 284:290 arg1 interleukin-25 312:325 interleukin-25 312:325 interleukin-25 312:325 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 1 17 theme barrier 186:192 arg1 epithelium 139:148 The epithelium 135:148 The epithelium 135:148 The epithelium is an integral component of mucosal barrier and host immunity. 35385697 1 17 theme barrier 186:192 arg1 component 165:173 an integral component 153:173 an integral component of mucosal barrier and host immunity 153:210 The epithelium is an integral component of mucosal barrier and host immunity. 35385697 2 18 theme immune 369:374 arg1 responses 376:384 the type 2 immune responses 358:384 the type 2 immune responses 358:384 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 5 19 theme Pou2f3 826:831 arg1 transcription 792:804 the transcription 788:804 the transcription of lineage-defining Pou2f3 788:831 By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. 35385697 8 20 theme anti-helminth 1113:1125 arg1 immunity 1127:1134 effective anti-helminth immunity 1103:1134 effective anti-helminth immunity 1103:1134 GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. 35385697 8 21 theme GSDMC-mediated 1050:1063 arg1 secretion 1071:1079 GSDMC-mediated IL-33 secretion 1050:1079 GSDMC-mediated IL-33 secretion 1050:1079 GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. 35385697 3 22 theme epithelial 510:519 arg1 remodeling 521:530 epithelial remodeling 510:530 epithelial remodeling 510:530 However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. 35385697 1 23 theme mucosal 178:184 arg1 barrier 186:192 mucosal barrier 178:192 mucosal barrier 178:192 The epithelium is an integral component of mucosal barrier and host immunity. 35385697 0 24 theme STAT6 11:15 arg1 O-GlcNAcylation 17:31 Epithelial STAT6 O-GlcNAcylation 0:31 Epithelial STAT6 O-GlcNAcylation 0:31 Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. 35385697 5 25 theme O-GlcNAc 758:765 arg1 transferase 767:777 O-GlcNAc transferase 758:777 O-GlcNAc transferase 758:777 By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. 35385697 2 26 theme type 362:365 arg1 responses 376:384 the type 2 immune responses 358:384 the type 2 immune responses 358:384 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 0 27 theme Epithelial 0:9 arg1 O-GlcNAcylation 17:31 Epithelial STAT6 O-GlcNAcylation 0:31 Epithelial STAT6 O-GlcNAcylation 0:31 Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. 35385697 6 28 theme STAT6 895:899 arg1 Meanwhile 884:892 Meanwhile 884:892 Meanwhile 884:892 Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. 35385697 6 28 theme STAT6 895:899 arg1 O-GlcNAcylation 901:915 STAT6 O-GlcNAcylation 895:915 STAT6 O-GlcNAcylation 895:915 Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. 35385697 5 29 theme cell 841:844 arg1 differentiation 846:860 tuft cell differentiation 836:860 tuft cell differentiation 836:860 By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. 35385697 5 30 theme tuft 836:839 arg1 differentiation 846:860 tuft cell differentiation 836:860 tuft cell differentiation 836:860 By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. 35385697 8 31 theme induced 1155:1161 arg1 inflammation 1174:1185 induced intestinal inflammation 1155:1185 induced intestinal inflammation 1155:1185 GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. 35385697 7 32 theme membrane 969:976 arg1 pore 978:981 The membrane pore 965:981 The membrane pore formed by GSDMC 965:997 The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. 35385697 9 33 theme Protein 1188:1194 arg1 O-GlcNAcylation 1196:1210 Protein O-GlcNAcylation 1188:1210 Protein O-GlcNAcylation 1188:1210 Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases. 35385697 1 34 theme host 198:201 arg1 immunity 203:210 host immunity 198:210 host immunity 198:210 The epithelium is an integral component of mucosal barrier and host immunity. 35385697 3 35 theme alarmin 548:554 arg1 secretion 556:564 alarmin secretion 548:564 alarmin secretion 548:564 However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. 35385697 1 36 theme immunity 203:210 arg1 epithelium 139:148 The epithelium 135:148 The epithelium 135:148 The epithelium is an integral component of mucosal barrier and host immunity. 35385697 1 36 theme immunity 203:210 arg1 component 165:173 an integral component 153:173 an integral component of mucosal barrier and host immunity 153:210 The epithelium is an integral component of mucosal barrier and host immunity. 35385697 0 37 theme concerted 42:50 arg1 response 74:81 a concerted anti-helminth alarmin response 40:81 a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C 40:132 Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. 35385697 4 38 link O-linked 599:606 arg1 O-GlcNAc 629:636 O-GlcNAc 629:636 O-GlcNAc 629:636 Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. 35385697 4 38 link O-linked 599:606 arg1 N-Acetylglucosamine 608:626 O-linked N-Acetylglucosamine 599:626 epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification 588:658 Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. 35385697 4 39 theme protein 639:645 arg1 modification 647:658 epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification 588:658 epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification 588:658 Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. 35385697 8 40 theme intestinal 1163:1172 arg1 inflammation 1174:1185 induced intestinal inflammation 1155:1185 induced intestinal inflammation 1155:1185 GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. 35385697 0 41 theme alarmin 66:72 arg1 response 74:81 a concerted anti-helminth alarmin response 40:81 a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C 40:132 Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. 35385697 0 42 theme anti-helminth 52:64 arg1 response 74:81 a concerted anti-helminth alarmin response 40:81 a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C 40:132 Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. 35385697 2 43 theme helminth 223:230 arg1 infection 232:240 helminth infection 223:240 helminth infection 223:240 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 8 44 theme IL-33 1065:1069 arg1 secretion 1071:1079 GSDMC-mediated IL-33 secretion 1050:1079 GSDMC-mediated IL-33 secretion 1050:1079 GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. 35385697 9 45 theme future 1233:1238 arg1 treatment 1240:1248 future treatment 1233:1248 future treatment of type 2 inflammation-associated human diseases 1233:1297 Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases. 35385697 9 46 theme type 1253:1256 arg1 diseases 1290:1297 type 2 inflammation-associated human diseases 1253:1297 type 2 inflammation-associated human diseases 1253:1297 Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases. 35385697 4 47 theme epithelial 588:597 arg1 modification 647:658 epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification 588:658 epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification 588:658 Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. 35385697 5 48 dep factor 744:749 arg1 STAT6 751:755 STAT6 751:755 the transcription factor STAT6 726:755 By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. 35385697 3 49 theme helminth 451:458 arg1 infection 460:468 helminth infection 451:468 helminth infection 451:468 However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. 35385697 0 50 theme dependent 83:91 arg1 response 74:81 a concerted anti-helminth alarmin response 40:81 a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C 40:132 Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. 35385697 2 51 theme epithelial 258:267 arg1 cells 269:273 the intestinal epithelial cells 243:273 the intestinal epithelial cells 243:273 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 7 52 theme IL-33 1043:1047 arg1 secretion 1030:1038 the unconventional secretion 1011:1038 the unconventional secretion of IL-33 1011:1047 The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. 35385697 3 53 theme cytokine 488:495 arg1 milieu 497:502 the resulting cytokine milieu 474:502 the resulting cytokine milieu 474:502 However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. 35385697 4 54 theme N-Acetylglucosamine 608:626 arg1 modification 647:658 epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification 588:658 epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification 588:658 Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. 35385697 5 55 theme lineage-defining 809:824 arg1 Pou2f3 826:831 lineage-defining Pou2f3 809:831 lineage-defining Pou2f3 809:831 By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. 35385697 2 56 theme intestinal 247:256 arg1 cells 269:273 the intestinal epithelial cells 243:273 the intestinal epithelial cells 243:273 Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. 35385697 7 57 theme unconventional 1015:1028 arg1 secretion 1030:1038 the unconventional secretion 1011:1038 the unconventional secretion of IL-33 1011:1047 The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. 35385697 4 58 theme helminth 677:684 arg1 infections 686:695 helminth infections 677:695 helminth infections 677:695 Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. 35385697 4 59 theme O-linked 599:606 arg1 O-GlcNAc 629:636 O-GlcNAc 629:636 O-GlcNAc 629:636 Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. 35385697 4 59 theme O-linked 599:606 arg1 N-Acetylglucosamine 608:626 O-linked N-Acetylglucosamine 599:626 epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification 588:658 Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. 36460670 4 0 from important 628:636 arg1 disease 658:664 disease 658:664 disease 658:664 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 4 0 from important 628:636 arg1 health 647:652 human health 641:652 human health 641:652 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 8 1 theme S-linked 1158:1165 arg1 analogs 1183:1189 S-linked heparan sulfate analogs 1158:1189 S-linked heparan sulfate analogs 1158:1189 S-linked heparan sulfate analogs are not cleaved by human heparanase. 36460670 7 2 theme chain 929:933 arg1 reactions 953:961 chain co-polymerization reactions 929:961 chain co-polymerization reactions with a second donor 929:981 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 8 3 theme human 1210:1214 arg1 heparanase 1216:1225 human heparanase 1210:1225 human heparanase 1210:1225 S-linked heparan sulfate analogs are not cleaved by human heparanase. 36460670 4 4 theme state 559:563 arg1 s 565:565 potentially altered conformational state(s) 524:566 potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease 524:664 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 5 5 theme artificial 670:679 arg1 donor 687:691 An artificial sugar donor 667:691 An artificial sugar donor with a sulfhydryl functionality 667:723 An artificial sugar donor with a sulfhydryl functionality is synthesized and enzymatically incorporated into polysaccharide chains utilizing heparosan synthase. 36460670 0 6 link sulfur-linked 28:40 arg1 polymers 48:55 sulfur-linked sugar polymers 28:55 sulfur-linked sugar polymers as heparanase inhibitors 28:80 Chemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors. 36460670 9 7 theme transition 1443:1452 arg1 state 1454:1458 the transition state 1439:1458 the transition state 1439:1458 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 3 8 theme potential 357:365 arg1 candidates 372:381 potential drug candidates 357:381 potential drug candidates that selectively alter or perturb metabolic processes 357:435 The design and synthesis of glycans as potential drug candidates that selectively alter or perturb metabolic processes is challenging. 36460670 4 9 theme conformational 544:557 arg1 s 565:565 potentially altered conformational state(s) 524:566 potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease 524:664 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 5 10 theme sugar 681:685 arg1 donor 687:691 An artificial sugar donor 667:691 An artificial sugar donor with a sulfhydryl functionality 667:723 An artificial sugar donor with a sulfhydryl functionality is synthesized and enzymatically incorporated into polysaccharide chains utilizing heparosan synthase. 36460670 9 11 theme state 1454:1458 arg1 aspects 1428:1434 aspects 1428:1434 aspects of the transition state 1428:1458 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 3 12 theme drug 367:370 arg1 candidates 372:381 potential drug candidates 357:381 potential drug candidates that selectively alter or perturb metabolic processes 357:435 The design and synthesis of glycans as potential drug candidates that selectively alter or perturb metabolic processes is challenging. 36460670 4 13 theme sulfur-linked 489:501 arg1 polysaccharides 503:517 the first reported sulfur-linked polysaccharides 470:517 the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease 470:664 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 7 14 theme natural 1133:1139 arg1 bond 1152:1155 a natural 'O-linked' bond 1131:1155 a natural 'O-linked' bond 1131:1155 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 7 15 theme thiol-terminated 989:1004 arg1 acceptor 1034:1041 an acceptor 1031:1041 an acceptor 1031:1041 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 7 15 theme thiol-terminated 989:1004 arg1 heparosan 1006:1014 this thiol-terminated heparosan 984:1014 this thiol-terminated heparosan 984:1014 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 3 16 theme glycans 346:352 arg1 synthesis 333:341 synthesis 333:341 synthesis 333:341 The design and synthesis of glycans as potential drug candidates that selectively alter or perturb metabolic processes is challenging. 36460670 3 16 theme glycans 346:352 arg1 design 322:327 design 322:327 design 322:327 The design and synthesis of glycans as potential drug candidates that selectively alter or perturb metabolic processes is challenging. 36460670 4 17 theme reported 480:487 arg1 polysaccharides 503:517 the first reported sulfur-linked polysaccharides 470:517 the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease 470:664 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 10 18 theme cancer 1499:1504 arg1 therapeutics 1506:1517 future cancer therapeutics 1492:1517 future cancer therapeutics 1492:1517 Our analogs form the basis for future cancer therapeutics and modulators of protein/sugar interactions. 36460670 1 19 theme Complex 83:89 arg1 glycans 106:112 glycans 106:112 glycans 106:112 Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. 36460670 1 19 theme Complex 83:89 arg1 carbohydrates 91:103 Complex carbohydrates 83:103 Complex carbohydrates (glycans) 83:113 Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. 36460670 1 19 theme Complex 83:89 arg1 players 125:131 major players 119:131 major players in all organisms due to their structural, energy, and communication roles 119:205 Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. 36460670 6 20 theme single 858:863 arg1 thio-sugar 865:874 a single thio-sugar 856:874 a single thio-sugar onto the termini of nascent chains 856:909 Used alone, this donor adds a single thio-sugar onto the termini of nascent chains. 36460670 3 21 theme metabolic 417:425 arg1 processes 427:435 metabolic processes 417:435 metabolic processes 417:435 The design and synthesis of glycans as potential drug candidates that selectively alter or perturb metabolic processes is challenging. 36460670 9 22 theme S-link 1393:1398 arg1 conformations 1408:1420 the S-link polymer conformations 1389:1420 the S-link polymer conformations 1389:1420 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 5 23 theme polysaccharide 776:789 arg1 chains 791:796 polysaccharide chains 776:796 polysaccharide chains utilizing heparosan synthase 776:825 An artificial sugar donor with a sulfhydryl functionality is synthesized and enzymatically incorporated into polysaccharide chains utilizing heparosan synthase. 36460670 7 24 with reactions 953:961 arg1 donor 977:981 a second donor 968:981 a second donor 968:981 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 0 25 theme Chemoenzymatic 0:13 arg1 synthesis 15:23 Chemoenzymatic synthesis 0:23 Chemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors 0:80 Chemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors. 36460670 9 26 theme molecular 1346:1354 arg1 simulations 1364:1374 molecular dynamic simulations 1346:1374 molecular dynamic simulations 1346:1374 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 5 27 with donor 687:691 arg1 functionality 711:723 a sulfhydryl functionality 698:723 a sulfhydryl functionality 698:723 An artificial sugar donor with a sulfhydryl functionality is synthesized and enzymatically incorporated into polysaccharide chains utilizing heparosan synthase. 36460670 7 28 theme second 970:975 arg1 donor 977:981 a second donor 968:981 a second donor 968:981 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 7 29 theme O-linked 1142:1149 arg1 bond 1152:1155 a natural 'O-linked' bond 1131:1155 a natural 'O-linked' bond 1131:1155 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 0 30 theme sulfur-linked 28:40 arg1 polymers 48:55 sulfur-linked sugar polymers 28:55 sulfur-linked sugar polymers as heparanase inhibitors 28:80 Chemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors. 36460670 9 31 theme dynamic 1356:1362 arg1 simulations 1364:1374 molecular dynamic simulations 1346:1374 molecular dynamic simulations 1346:1374 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 3 32 dep design 322:327 arg1 The 318:320 The 318:320 The 318:320 The design and synthesis of glycans as potential drug candidates that selectively alter or perturb metabolic processes is challenging. 36460670 1 33 from players 125:131 arg1 organisms 140:148 all organisms 136:148 all organisms due to their structural, energy, and communication roles 136:205 Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. 36460670 2 34 theme proteins 308:315 arg1 plethora 281:288 a plethora 279:288 a plethora of glycan-binding proteins 279:315 This last essential role involves interacting and/or signaling through a plethora of glycan-binding proteins. 36460670 4 35 from disease 658:664 arg1 important 628:636 important 628:636 important 628:636 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 7 36 theme sugar 1104:1108 arg1 residues 1110:1117 sugar residues 1104:1117 sugar residues in place of a natural 'O-linked' bond 1104:1155 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 2 37 theme glycan-binding 293:306 arg1 proteins 308:315 glycan-binding proteins 293:315 glycan-binding proteins 293:315 This last essential role involves interacting and/or signaling through a plethora of glycan-binding proteins. 36460670 1 38 theme communication 187:199 arg1 roles 201:205 communication roles 187:205 communication roles 187:205 Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. 36460670 0 39 theme polymers 48:55 arg1 synthesis 15:23 Chemoenzymatic synthesis 0:23 Chemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors 0:80 Chemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors. 36460670 6 40 theme chains 904:909 arg1 termini 885:891 the termini 881:891 the termini of nascent chains 881:909 Used alone, this donor adds a single thio-sugar onto the termini of nascent chains. 36460670 4 41 from health 647:652 arg1 important 628:636 important 628:636 important 628:636 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 0 42 theme sugar 42:46 arg1 polymers 48:55 sulfur-linked sugar polymers 28:55 sulfur-linked sugar polymers as heparanase inhibitors 28:80 Chemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors. 36460670 6 43 theme nascent 896:902 arg1 chains 904:909 nascent chains 896:909 nascent chains 896:909 Used alone, this donor adds a single thio-sugar onto the termini of nascent chains. 36460670 2 44 theme essential 218:226 arg1 role 228:231 This last essential role 208:231 This last essential role 208:231 This last essential role involves interacting and/or signaling through a plethora of glycan-binding proteins. 36460670 7 45 theme unnatural 1054:1062 arg1 bond 1080:1083 an unnatural thio-glycosidic bond 1051:1083 an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond 1051:1155 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 7 45 theme unnatural 1054:1062 arg1 -link 1088:1092 'S-link' 1086:1093 'S-link' 1086:1093 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 7 46 link O-linked 1142:1149 arg1 bond 1152:1155 a natural 'O-linked' bond 1131:1155 a natural 'O-linked' bond 1131:1155 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 0 47 theme heparanase 60:69 arg1 inhibitors 71:80 heparanase inhibitors 60:80 heparanase inhibitors 60:80 Chemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors. 36460670 8 48 theme sulfate 1175:1181 arg1 analogs 1183:1189 S-linked heparan sulfate analogs 1158:1189 S-linked heparan sulfate analogs 1158:1189 S-linked heparan sulfate analogs are not cleaved by human heparanase. 36460670 2 49 theme last 213:216 arg1 role 228:231 This last essential role 208:231 This last essential role 208:231 This last essential role involves interacting and/or signaling through a plethora of glycan-binding proteins. 36460670 7 50 theme thio-glycosidic 1064:1078 arg1 bond 1080:1083 an unnatural thio-glycosidic bond 1051:1083 an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond 1051:1155 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 7 50 theme thio-glycosidic 1064:1078 arg1 -link 1088:1092 'S-link' 1086:1093 'S-link' 1086:1093 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 1 51 theme major 119:123 arg1 carbohydrates 91:103 Complex carbohydrates 83:103 Complex carbohydrates (glycans) 83:113 Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. 36460670 1 51 theme major 119:123 arg1 players 125:131 major players 119:131 major players in all organisms due to their structural, energy, and communication roles 119:205 Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. 36460670 4 52 link sulfur-linked 489:501 arg1 polysaccharides 503:517 the first reported sulfur-linked polysaccharides 470:517 the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease 470:664 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 9 53 theme competitive 1260:1270 arg1 inhibitors 1272:1281 competitive inhibitors 1260:1281 competitive inhibitors 1260:1281 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 9 53 theme competitive 1260:1270 arg1 potency 1307:1313 with > ~200-fold higher potency than expected 1283:1327 with > ~200-fold higher potency than expected 1283:1327 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 9 53 theme competitive 1260:1270 arg1 analogs 1245:1251 the analogs 1241:1251 the analogs 1241:1251 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 10 54 theme future 1492:1497 arg1 therapeutics 1506:1517 future cancer therapeutics 1492:1517 future cancer therapeutics 1492:1517 Our analogs form the basis for future cancer therapeutics and modulators of protein/sugar interactions. 36460670 9 55 theme polymer 1400:1406 arg1 conformations 1408:1420 the S-link polymer conformations 1389:1420 the S-link polymer conformations 1389:1420 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 5 56 theme sulfhydryl 700:709 arg1 functionality 711:723 a sulfhydryl functionality 698:723 a sulfhydryl functionality 698:723 An artificial sugar donor with a sulfhydryl functionality is synthesized and enzymatically incorporated into polysaccharide chains utilizing heparosan synthase. 36460670 4 57 theme important 628:636 arg1 heparanase 606:615 heparanase 606:615 heparanase 606:615 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 4 57 theme important 628:636 arg1 enzyme 621:626 an enzyme 618:626 an enzyme important in human health and disease 618:664 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 10 58 theme protein/sugar 1537:1549 arg1 interactions 1551:1562 protein/sugar interactions 1537:1562 protein/sugar interactions 1537:1562 Our analogs form the basis for future cancer therapeutics and modulators of protein/sugar interactions. 36460670 8 59 link S-linked 1158:1165 arg1 analogs 1183:1189 S-linked heparan sulfate analogs 1158:1189 S-linked heparan sulfate analogs 1158:1189 S-linked heparan sulfate analogs are not cleaved by human heparanase. 36460670 4 60 with polysaccharides 503:517 arg1 s 565:565 potentially altered conformational state(s) 524:566 potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease 524:664 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 7 61 theme co-polymerization 935:951 arg1 reactions 953:961 chain co-polymerization reactions 929:961 chain co-polymerization reactions with a second donor 929:981 Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic bond ('S-link') between sugar residues in place of a natural 'O-linked' bond. 36460670 9 62 theme higher 1300:1305 arg1 inhibitors 1272:1281 competitive inhibitors 1260:1281 competitive inhibitors 1260:1281 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 9 62 theme higher 1300:1305 arg1 potency 1307:1313 with > ~200-fold higher potency than expected 1283:1327 with > ~200-fold higher potency than expected 1283:1327 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 9 62 theme higher 1300:1305 arg1 analogs 1245:1251 the analogs 1241:1251 the analogs 1241:1251 Furthermore, the analogs act as competitive inhibitors with > ~200-fold higher potency than expected; as a rationale, molecular dynamic simulations suggest that the S-link polymer conformations mimic aspects of the transition state. 36460670 10 63 theme interactions 1551:1562 arg1 modulators 1523:1532 modulators 1523:1532 modulators of protein/sugar interactions 1523:1562 Our analogs form the basis for future cancer therapeutics and modulators of protein/sugar interactions. 36460670 10 63 theme interactions 1551:1562 arg1 therapeutics 1506:1517 future cancer therapeutics 1492:1517 future cancer therapeutics 1492:1517 Our analogs form the basis for future cancer therapeutics and modulators of protein/sugar interactions. 36460670 4 64 theme human 641:645 arg1 health 647:652 human health 641:652 human health 641:652 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 5 65 theme heparosan 808:816 arg1 synthase 818:825 heparosan synthase 808:825 heparosan synthase 808:825 An artificial sugar donor with a sulfhydryl functionality is synthesized and enzymatically incorporated into polysaccharide chains utilizing heparosan synthase. 36460670 4 66 theme altered 536:542 arg1 s 565:565 potentially altered conformational state(s) 524:566 potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease 524:664 Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. 36460670 1 67 theme due 150:152 arg1 organisms 140:148 all organisms 136:148 all organisms due to their structural, energy, and communication roles 136:205 Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. 36460670 8 68 theme heparan 1167:1173 arg1 analogs 1183:1189 S-linked heparan sulfate analogs 1158:1189 S-linked heparan sulfate analogs 1158:1189 S-linked heparan sulfate analogs are not cleaved by human heparanase. 36961502 3 0 theme resistance 341:350 arg1 signature 310:318 a pan-cancer signature 297:318 a pan-cancer signature of both response and resistance to multiple targeted therapies 297:381 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 3 0 theme resistance 341:350 arg1 fucosylation 281:292 an elevated secretome fucosylation 259:292 an elevated secretome fucosylation 259:292 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 7 1 theme fucosylation 875:886 arg1 N-glycosylation 836:850 N-glycosylation 836:850 N-glycosylation of TIS and target core fucosylation of PON1 836:894 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 8 2 theme degradation-resistant 1118:1138 arg1 PON1 1140:1143 a more degradation-resistant PON1 1111:1143 a more degradation-resistant PON1 1111:1143 Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. 36961502 6 3 theme therapy-induced 803:817 arg1 TIS 830:832 TIS 830:832 TIS 830:832 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 6 3 theme therapy-induced 803:817 arg1 secretome 819:827 the therapy-induced secretome 799:827 the therapy-induced secretome (TIS) 799:833 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 7 4 gly fucosylation 875:886 arg1 PON1 891:894 PON1 891:894 PON1 891:894 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 9 5 theme clones 1240:1245 arg1 expansion 1217:1225 the expansion 1213:1225 the expansion of resistant clones in a tumor regression model 1213:1273 Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. 36961502 7 6 theme PON1 891:894 arg1 TIS 855:857 TIS 855:857 TIS 855:857 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 7 6 theme PON1 891:894 arg1 fucosylation 875:886 target core fucosylation 863:886 target core fucosylation 863:886 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 4 7 theme widespread 454:463 arg1 association 465:475 widespread association 454:475 widespread association with resistance to these therapies 454:510 Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. 36961502 9 8 theme PON1-specific 1157:1169 arg1 de-N-glycosylation 1181:1198 Global and PON1-specific secretome de-N-glycosylation 1146:1198 Global and PON1-specific secretome de-N-glycosylation 1146:1198 Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. 36961502 7 9 gly N-glycosylation 836:850 arg1 TIS 855:857 TIS 855:857 TIS 855:857 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 7 9 gly N-glycosylation 836:850 arg1 fucosylation 875:886 target core fucosylation 863:886 target core fucosylation 863:886 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 10 10 gly N-glycosylated 1368:1381 arg1 TIS 1383:1385 the N-glycosylated TIS 1364:1385 the N-glycosylated TIS 1364:1385 We defined the resistance-associated transcription factors (TFs) and genes modulated by the N-glycosylated TIS via a focused and transcriptome-wide analyses. 36961502 1 11 theme Cancer 75:80 arg1 secretome 82:90 Cancer secretome 75:90 Cancer secretome 75:90 Cancer secretome is a reservoir for aberrant glycosylation. 36961502 1 11 theme Cancer 75:80 arg1 reservoir 97:105 a reservoir 95:105 a reservoir for aberrant glycosylation 95:132 Cancer secretome is a reservoir for aberrant glycosylation. 36961502 6 12 theme Label-free 682:691 arg1 proteomics 693:702 Label-free proteomics 682:702 Label-free proteomics of N-glycoproteomes 682:722 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 6 13 theme N-glycoproteomes 707:722 arg1 proteomics 693:702 Label-free proteomics 682:702 Label-free proteomics of N-glycoproteomes 682:722 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 2 14 theme cancer 180:185 arg1 hallmark 187:194 this post- translational cancer hallmark 155:194 this post- translational cancer hallmark 155:194 How therapies alter this post- translational cancer hallmark and the consequences thereof remain elusive. 36961502 6 15 theme PON1 767:770 arg1 fucosylation 735:746 fucosylation 735:746 fucosylation of the antioxidant PON1 735:770 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 6 15 theme PON1 767:770 arg1 component 786:794 a critical component 775:794 a critical component of the therapy-induced secretome (TIS) 775:833 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 9 16 theme Global 1146:1151 arg1 de-N-glycosylation 1181:1198 Global and PON1-specific secretome de-N-glycosylation 1146:1198 Global and PON1-specific secretome de-N-glycosylation 1146:1198 Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. 36961502 9 17 theme resistant 1230:1238 arg1 clones 1240:1245 resistant clones 1230:1245 resistant clones 1230:1245 Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. 36961502 2 18 theme translational 166:178 arg1 hallmark 187:194 this post- translational cancer hallmark 155:194 this post- translational cancer hallmark 155:194 How therapies alter this post- translational cancer hallmark and the consequences thereof remain elusive. 36961502 3 19 theme secretome 271:279 arg1 signature 310:318 a pan-cancer signature 297:318 a pan-cancer signature of both response and resistance to multiple targeted therapies 297:381 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 3 19 theme secretome 271:279 arg1 fucosylation 281:292 an elevated secretome fucosylation 259:292 an elevated secretome fucosylation 259:292 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 10 20 theme N-glycosylated 1368:1381 arg1 TIS 1383:1385 the N-glycosylated TIS 1364:1385 the N-glycosylated TIS 1364:1385 We defined the resistance-associated transcription factors (TFs) and genes modulated by the N-glycosylated TIS via a focused and transcriptome-wide analyses. 36961502 10 21 theme transcriptome-wide 1405:1422 arg1 analyses 1424:1431 transcriptome-wide analyses 1405:1431 transcriptome-wide analyses 1405:1431 We defined the resistance-associated transcription factors (TFs) and genes modulated by the N-glycosylated TIS via a focused and transcriptome-wide analyses. 36961502 2 22 theme post- 160:164 arg1 hallmark 187:194 this post- translational cancer hallmark 155:194 this post- translational cancer hallmark 155:194 How therapies alter this post- translational cancer hallmark and the consequences thereof remain elusive. 36961502 7 23 theme salvage-FUT8-SLC35C1 923:942 arg1 axis 944:947 the fucose salvage-FUT8-SLC35C1 axis 912:947 the fucose salvage-FUT8-SLC35C1 axis with PON3 912:957 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 11 24 theme important 1534:1542 arg1 stress 1473:1478 the oxidative stress 1459:1478 the oxidative stress 1459:1478 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 24 theme important 1534:1542 arg1 factors 1544:1550 important factors 1534:1550 important factors for this modulation 1534:1570 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 24 theme important 1534:1542 arg1 response 1522:1529 unfolded protein response 1505:1529 unfolded protein response 1505:1529 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 24 theme important 1534:1542 arg1 niche 1494:1498 inflammatory niche 1481:1498 inflammatory niche 1481:1498 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 0 25 theme therapy 15:21 arg1 resistance 23:32 therapy resistance 15:32 therapy resistance 15:32 Multi-targeted therapy resistance via drug-induced secretome fucosylation. 36961502 6 26 gly fucosylation 735:746 arg1 PON1 767:770 the antioxidant PON1 751:770 the antioxidant PON1 751:770 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 5 27 theme secreted 646:653 arg1 proteins 655:662 secreted proteins 646:662 secreted proteins less than 60 kDa 646:679 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 6 28 theme critical 777:784 arg1 component 786:794 a critical component 775:794 a critical component of the therapy-induced secretome (TIS) 775:833 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 6 28 theme critical 777:784 arg1 fucosylation 735:746 fucosylation 735:746 fucosylation of the antioxidant PON1 735:770 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 8 29 from fucosylation 1020:1031 arg1 Golgi 1040:1044 the Golgi 1036:1044 the Golgi 1036:1044 Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. 36961502 4 30 with association 465:475 arg1 resistance 482:491 resistance 482:491 resistance to these therapies 482:510 Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. 36961502 5 31 gly induced 617:623 arg1 cultures 528:535 cancer cell cultures 516:535 cancer cell cultures 516:535 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 5 31 gly induced 617:623 arg1 models 554:559 xenograft mouse models 538:559 xenograft mouse models 538:559 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 5 31 gly induced 617:623 arg1 patients 566:573 patients 566:573 patients 566:573 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 3 32 theme elevated 262:269 arg1 signature 310:318 a pan-cancer signature 297:318 a pan-cancer signature of both response and resistance to multiple targeted therapies 297:381 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 3 32 theme elevated 262:269 arg1 fucosylation 281:292 an elevated secretome fucosylation 259:292 an elevated secretome fucosylation 259:292 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 5 33 theme proteins 655:662 arg1 fucosylation 630:641 core fucosylation 625:641 core fucosylation of secreted proteins less than 60 kDa 625:679 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 8 34 theme PON1 1054:1057 arg1 stability 1059:1067 PON1 stability 1054:1067 PON1 stability 1054:1067 Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. 36961502 11 35 theme unfolded 1505:1512 arg1 response 1522:1529 unfolded protein response 1505:1529 unfolded protein response 1505:1529 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 35 theme unfolded 1505:1512 arg1 factors 1544:1550 important factors 1534:1550 important factors for this modulation 1534:1570 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 35 theme unfolded 1505:1512 arg1 niche 1494:1498 inflammatory niche 1481:1498 inflammatory niche 1481:1498 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 35 theme unfolded 1505:1512 arg1 stress 1473:1478 the oxidative stress 1459:1478 the oxidative stress 1459:1478 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 3 36 theme pan-cancer 299:308 arg1 signature 310:318 a pan-cancer signature 297:318 a pan-cancer signature of both response and resistance to multiple targeted therapies 297:381 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 3 36 theme pan-cancer 299:308 arg1 fucosylation 281:292 an elevated secretome fucosylation 259:292 an elevated secretome fucosylation 259:292 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 4 37 theme fucosylation 427:438 arg1 genes 440:444 fucosylation genes 427:444 fucosylation genes 427:444 Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. 36961502 1 38 theme aberrant 111:118 arg1 glycosylation 120:132 aberrant glycosylation 111:132 aberrant glycosylation 111:132 Cancer secretome is a reservoir for aberrant glycosylation. 36961502 7 39 theme fucose 916:921 arg1 axis 944:947 the fucose salvage-FUT8-SLC35C1 axis 912:947 the fucose salvage-FUT8-SLC35C1 axis with PON3 912:957 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 11 40 theme oxidative 1463:1471 arg1 stress 1473:1478 the oxidative stress 1459:1478 the oxidative stress 1459:1478 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 40 theme oxidative 1463:1471 arg1 factors 1544:1550 important factors 1534:1550 important factors for this modulation 1534:1570 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 40 theme oxidative 1463:1471 arg1 response 1522:1529 unfolded protein response 1505:1529 unfolded protein response 1505:1529 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 40 theme oxidative 1463:1471 arg1 niche 1494:1498 inflammatory niche 1481:1498 inflammatory niche 1481:1498 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 5 41 gly fucosylation 630:641 arg1 proteins 655:662 secreted proteins 646:662 secreted proteins less than 60 kDa 646:679 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 9 42 theme tumor 1252:1256 arg1 model 1269:1273 a tumor regression model 1250:1273 a tumor regression model 1250:1273 Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. 36961502 6 43 theme antioxidant 755:765 arg1 PON1 767:770 the antioxidant PON1 751:770 the antioxidant PON1 751:770 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 5 44 theme xenograft 538:546 arg1 models 554:559 xenograft mouse models 538:559 xenograft mouse models 538:559 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 0 45 theme secretome 51:59 arg1 fucosylation 61:72 drug-induced secretome fucosylation 38:72 drug-induced secretome fucosylation 38:72 Multi-targeted therapy resistance via drug-induced secretome fucosylation. 36961502 5 46 theme mouse 548:552 arg1 models 554:559 xenograft mouse models 538:559 xenograft mouse models 538:559 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 7 47 theme GDP-Fuc 979:985 arg1 transfer 987:994 GDP-Fuc transfer 979:994 GDP-Fuc transfer 979:994 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 0 48 theme drug-induced 38:49 arg1 fucosylation 61:72 drug-induced secretome fucosylation 38:72 drug-induced secretome fucosylation 38:72 Multi-targeted therapy resistance via drug-induced secretome fucosylation. 36961502 7 49 theme target 863:868 arg1 fucosylation 875:886 target core fucosylation 863:886 target core fucosylation 863:886 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 7 50 theme PON1 999:1002 arg1 scaffolds 1004:1012 PON1 scaffolds 999:1012 PON1 scaffolds 999:1012 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 12 51 theme targeted 1668:1675 arg1 therapies 1677:1685 targeted therapies 1668:1685 targeted therapies 1668:1685 Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance. 36961502 11 52 theme inflammatory 1481:1492 arg1 stress 1473:1478 the oxidative stress 1459:1478 the oxidative stress 1459:1478 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 52 theme inflammatory 1481:1492 arg1 niche 1494:1498 inflammatory niche 1481:1498 inflammatory niche 1481:1498 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 52 theme inflammatory 1481:1492 arg1 response 1522:1529 unfolded protein response 1505:1529 unfolded protein response 1505:1529 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 52 theme inflammatory 1481:1492 arg1 factors 1544:1550 important factors 1534:1550 important factors for this modulation 1534:1570 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 7 53 theme core 870:873 arg1 fucosylation 875:886 target core fucosylation 863:886 target core fucosylation 863:886 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 3 54 theme response 328:335 arg1 signature 310:318 a pan-cancer signature 297:318 a pan-cancer signature of both response and resistance to multiple targeted therapies 297:381 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 3 54 theme response 328:335 arg1 fucosylation 281:292 an elevated secretome fucosylation 259:292 an elevated secretome fucosylation 259:292 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 8 55 gly fucosylation 1020:1031 arg1 Golgi 1040:1044 the Golgi 1036:1044 the Golgi 1036:1044 Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. 36961502 9 56 from expansion 1217:1225 arg1 model 1269:1273 a tumor regression model 1250:1273 a tumor regression model 1250:1273 Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. 36961502 8 57 theme Core 1015:1018 arg1 fucosylation 1020:1031 Core fucosylation 1015:1031 Core fucosylation in the Golgi 1015:1044 Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. 36961502 12 58 theme core 1603:1606 arg1 modification 1633:1644 a common modification 1624:1644 a common modification indirectly induced by targeted therapies that paradoxically promotes resistance 1624:1724 Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance. 36961502 12 58 theme core 1603:1606 arg1 fucosylation 1608:1619 core fucosylation 1603:1619 core fucosylation 1603:1619 Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance. 36961502 7 59 theme TIS 855:857 arg1 N-glycosylation 836:850 N-glycosylation 836:850 N-glycosylation of TIS and target core fucosylation of PON1 836:894 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 5 60 theme core 625:628 arg1 fucosylation 630:641 core fucosylation 625:641 core fucosylation of secreted proteins less than 60 kDa 625:679 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 5 61 dep kDa 677:679 arg1 60 674:675 60 674:675 60 674:675 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 7 62 with axis 944:947 arg1 PON3 954:957 PON3 954:957 PON3 954:957 N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. 36961502 4 63 theme Large-scale 384:394 arg1 pharmacogenomics 396:411 Large-scale pharmacogenomics 384:411 Large-scale pharmacogenomics 384:411 Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. 36961502 11 64 theme protein 1514:1520 arg1 response 1522:1529 unfolded protein response 1505:1529 unfolded protein response 1505:1529 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 64 theme protein 1514:1520 arg1 factors 1544:1550 important factors 1534:1550 important factors for this modulation 1534:1570 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 64 theme protein 1514:1520 arg1 niche 1494:1498 inflammatory niche 1481:1498 inflammatory niche 1481:1498 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 11 64 theme protein 1514:1520 arg1 stress 1473:1478 the oxidative stress 1459:1478 the oxidative stress 1459:1478 These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. 36961502 6 65 theme secretome 819:827 arg1 component 786:794 a critical component 775:794 a critical component of the therapy-induced secretome (TIS) 775:833 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 6 65 theme secretome 819:827 arg1 fucosylation 735:746 fucosylation 735:746 fucosylation of the antioxidant PON1 735:770 Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). 36961502 9 66 theme regression 1258:1267 arg1 model 1269:1273 a tumor regression model 1250:1273 a tumor regression model 1250:1273 Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. 36961502 9 67 dep de-N-glycosylation 1181:1198 arg1 both 1200:1203 both 1200:1203 both 1200:1203 Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. 36961502 5 68 theme cancer 516:521 arg1 cultures 528:535 cancer cell cultures 516:535 cancer cell cultures 516:535 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 10 69 theme transcription 1313:1325 arg1 TFs 1336:1338 TFs 1336:1338 TFs 1336:1338 We defined the resistance-associated transcription factors (TFs) and genes modulated by the N-glycosylated TIS via a focused and transcriptome-wide analyses. 36961502 10 69 theme transcription 1313:1325 arg1 factors 1327:1333 the resistance-associated transcription factors 1287:1333 the resistance-associated transcription factors (TFs) 1287:1339 We defined the resistance-associated transcription factors (TFs) and genes modulated by the N-glycosylated TIS via a focused and transcriptome-wide analyses. 36961502 3 70 theme multiple 355:362 arg1 therapies 373:381 multiple targeted therapies 355:381 multiple targeted therapies 355:381 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 9 71 theme secretome 1171:1179 arg1 de-N-glycosylation 1181:1198 Global and PON1-specific secretome de-N-glycosylation 1146:1198 Global and PON1-specific secretome de-N-glycosylation 1146:1198 Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. 36961502 5 72 theme targeted 576:583 arg1 inhibitors 592:601 targeted kinase inhibitors 576:601 targeted kinase inhibitors 576:601 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 5 73 theme cell 523:526 arg1 cultures 528:535 cancer cell cultures 516:535 cancer cell cultures 516:535 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 10 74 theme resistance-associated 1291:1311 arg1 TFs 1336:1338 TFs 1336:1338 TFs 1336:1338 We defined the resistance-associated transcription factors (TFs) and genes modulated by the N-glycosylated TIS via a focused and transcriptome-wide analyses. 36961502 10 74 theme resistance-associated 1291:1311 arg1 factors 1327:1333 the resistance-associated transcription factors 1287:1333 the resistance-associated transcription factors (TFs) 1287:1339 We defined the resistance-associated transcription factors (TFs) and genes modulated by the N-glycosylated TIS via a focused and transcriptome-wide analyses. 36961502 3 75 theme targeted 364:371 arg1 therapies 373:381 multiple targeted therapies 355:381 multiple targeted therapies 355:381 Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. 36961502 5 76 theme kinase 585:590 arg1 inhibitors 592:601 targeted kinase inhibitors 576:601 targeted kinase inhibitors 576:601 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 5 77 dep proteins 655:662 arg1 kDa 677:679 kDa 677:679 kDa 677:679 In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. 36961502 12 78 theme common 1626:1631 arg1 modification 1633:1644 a common modification 1624:1644 a common modification indirectly induced by targeted therapies that paradoxically promotes resistance 1624:1724 Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance. 36961502 12 78 theme common 1626:1631 arg1 fucosylation 1608:1619 core fucosylation 1603:1619 core fucosylation 1603:1619 Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance. 36121863 10 0 theme broad 1582:1586 arg1 ML099 1603:1607 the broad GTPase agonist ML099 1578:1607 the broad GTPase agonist ML099 1578:1607 By contrast, the broad GTPase agonist ML099 countered the effects of 6-TG, suggesting that the antiviral activity of 6-TG requires the targeting of an unknown GTPase. 36121863 9 1 theme nucleotide 1362:1371 arg1 form 1373:1376 This nucleotide form 1357:1376 This nucleotide form 1357:1376 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 5 2 theme SARS-CoV-2 679:688 arg1 VLPs 712:715 VLPs 712:715 VLPs 712:715 SARS-CoV-2 virus-like particles (VLPs) harvested from 6-TG-treated cells were deficient in Spike. 36121863 5 2 theme SARS-CoV-2 679:688 arg1 particles 701:709 SARS-CoV-2 virus-like particles 679:709 SARS-CoV-2 virus-like particles (VLPs) harvested from 6-TG-treated cells 679:750 SARS-CoV-2 virus-like particles (VLPs) harvested from 6-TG-treated cells were deficient in Spike. 36121863 8 3 dep demonstrated 1191:1202 arg1 Using 1147:1151 Using 1147:1151 Using biochemical and genetic approaches 1147:1186 Using biochemical and genetic approaches we demonstrated that 6-TG is a pro-drug that must be converted to the nucleotide form by hypoxanthine phosphoribosyltransferase 1 (HPRT1) to achieve antiviral activity. 36121863 11 4 theme host-targeted 1809:1821 arg1 antivirals 1823:1832 host-targeted antivirals 1809:1832 host-targeted antivirals 1809:1832 Overall, these findings suggest that small GTPases are promising targets for host-targeted antivirals. 36121863 3 5 theme early 335:339 arg1 stages 341:346 early stages 335:346 early stages of infection 335:359 6-Thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. 36121863 5 6 theme virus-like 690:699 arg1 VLPs 712:715 VLPs 712:715 VLPs 712:715 SARS-CoV-2 virus-like particles (VLPs) harvested from 6-TG-treated cells were deficient in Spike. 36121863 5 6 theme virus-like 690:699 arg1 particles 701:709 SARS-CoV-2 virus-like particles 679:709 SARS-CoV-2 virus-like particles (VLPs) harvested from 6-TG-treated cells 679:750 SARS-CoV-2 virus-like particles (VLPs) harvested from 6-TG-treated cells were deficient in Spike. 36121863 6 7 theme SARS-CoV-2 860:869 arg1 Spike 871:875 SARS-CoV-2 Spike 860:875 SARS-CoV-2 Spike 860:875 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 6 8 theme deficient 901:909 arg1 pseudoviruses 887:899 pseudoviruses 887:899 pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells 887:961 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 5 9 from deficient 757:765 arg1 Spike 770:774 Spike 770:774 Spike 770:774 SARS-CoV-2 virus-like particles (VLPs) harvested from 6-TG-treated cells were deficient in Spike. 36121863 4 10 from removal 621:627 arg1 Spike 663:667 Spike 663:667 Spike 663:667 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 4 11 theme electrophoretic 521:535 arg1 mobility 537:544 the electrophoretic mobility 517:544 the electrophoretic mobility of Spike 517:553 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 10 12 theme agonist 1595:1601 arg1 ML099 1603:1607 the broad GTPase agonist ML099 1578:1607 the broad GTPase agonist ML099 1578:1607 By contrast, the broad GTPase agonist ML099 countered the effects of 6-TG, suggesting that the antiviral activity of 6-TG requires the targeting of an unknown GTPase. 36121863 7 13 theme infection 1031:1039 arg1 models 1041:1046 infection models 1031:1046 infection models 1031:1046 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 4 14 theme removal 621:627 arg1 effects 600:606 the effects 596:606 the effects of enzymatic removal of N-linked oligosaccharides from Spike 596:667 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 6 15 theme ACE2-expressing 941:955 arg1 cells 957:961 ACE2-expressing cells 941:961 ACE2-expressing cells 941:961 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 7 16 theme ectopic 1008:1014 arg1 expression 1016:1025 complementary ectopic expression 994:1025 complementary ectopic expression 994:1025 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 4 17 theme enzymatic 611:619 arg1 removal 621:627 enzymatic removal 611:627 enzymatic removal of N-linked oligosaccharides from Spike 611:667 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 3 18 theme infection 351:359 arg1 stages 341:346 early stages 335:346 early stages of infection 335:359 6-Thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. 36121863 6 19 theme lentiviruses 830:841 arg1 production 816:825 production 816:825 production of lentiviruses pseudotyped with SARS-CoV-2 Spike 816:875 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 10 20 theme GTPase 1588:1593 arg1 ML099 1603:1607 the broad GTPase agonist ML099 1578:1607 the broad GTPase agonist ML099 1578:1607 By contrast, the broad GTPase agonist ML099 countered the effects of 6-TG, suggesting that the antiviral activity of 6-TG requires the targeting of an unknown GTPase. 36121863 2 21 dep betacoronaviruses 260:276 arg1 SARS-CoV-2 292:301 SARS-CoV-2 292:301 SARS-CoV-2 292:301 Here, we report that thiopurines inhibit the replication of the betacoronaviruses HCoV-OC43 and SARS-CoV-2. 36121863 2 21 dep betacoronaviruses 260:276 arg1 HCoV-OC43 278:286 HCoV-OC43 278:286 HCoV-OC43 278:286 Here, we report that thiopurines inhibit the replication of the betacoronaviruses HCoV-OC43 and SARS-CoV-2. 36121863 2 21 dep betacoronaviruses 260:276 arg1 betacoronaviruses 260:276 the betacoronaviruses HCoV-OC43 and SARS-CoV-2 256:301 the betacoronaviruses HCoV-OC43 and SARS-CoV-2 256:301 Here, we report that thiopurines inhibit the replication of the betacoronaviruses HCoV-OC43 and SARS-CoV-2. 36121863 1 22 theme emerging 171:178 arg1 diseases 186:193 emerging viral diseases 171:193 emerging viral diseases 171:193 There is an outstanding need for broadly acting antiviral drugs to combat emerging viral diseases. 36121863 9 23 theme chemical 1477:1484 arg1 inhibitors 1486:1495 selective chemical inhibitors 1467:1495 selective chemical inhibitors of these GTPases 1467:1512 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 8 24 theme hypoxanthine 1277:1288 arg1 phosphoribosyltransferase 1290:1314 hypoxanthine phosphoribosyltransferase 1 1277:1316 hypoxanthine phosphoribosyltransferase 1 (HPRT1) 1277:1324 Using biochemical and genetic approaches we demonstrated that 6-TG is a pro-drug that must be converted to the nucleotide form by hypoxanthine phosphoribosyltransferase 1 (HPRT1) to achieve antiviral activity. 36121863 8 24 theme hypoxanthine 1277:1288 arg1 HPRT1 1319:1323 HPRT1 1319:1323 HPRT1 1319:1323 Using biochemical and genetic approaches we demonstrated that 6-TG is a pro-drug that must be converted to the nucleotide form by hypoxanthine phosphoribosyltransferase 1 (HPRT1) to achieve antiviral activity. 36121863 6 25 contain had 792:794 arg2 effect 806:811 a similar effect 796:811 a similar effect 796:811 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 6 25 contain had 792:794 arg1 treatment 782:790 6-TG treatment 777:790 6-TG treatment 777:790 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 1 26 theme viral 180:184 arg1 diseases 186:193 emerging viral diseases 171:193 emerging viral diseases 171:193 There is an outstanding need for broadly acting antiviral drugs to combat emerging viral diseases. 36121863 3 27 theme viral 399:403 arg1 genomes 405:411 full-length viral genomes 387:411 full-length viral genomes 387:411 6-Thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. 36121863 6 28 theme unable 924:929 arg1 pseudoviruses 887:899 pseudoviruses 887:899 pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells 887:961 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 7 29 theme complementary 994:1006 arg1 expression 1016:1025 complementary ectopic expression 994:1025 complementary ectopic expression 994:1025 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 8 30 theme biochemical 1153:1163 arg1 approaches 1177:1186 biochemical and genetic approaches 1153:1186 biochemical and genetic approaches 1153:1186 Using biochemical and genetic approaches we demonstrated that 6-TG is a pro-drug that must be converted to the nucleotide form by hypoxanthine phosphoribosyltransferase 1 (HPRT1) to achieve antiviral activity. 36121863 3 31 theme structural 434:443 arg1 proteins 445:452 structural proteins 434:452 structural proteins 434:452 6-Thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. 36121863 3 32 theme genomes 405:411 arg1 accumulation 371:382 accumulation 371:382 accumulation of full-length viral genomes, subgenomic RNAs and structural proteins 371:452 6-Thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. 36121863 9 33 theme small 1404:1408 arg1 Rac1 1418:1421 Rac1 1418:1421 Rac1 1418:1421 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 9 33 theme small 1404:1408 arg1 GTPases 1410:1416 small GTPases Rac1, RhoA, and CDC42 1404:1438 small GTPases Rac1, RhoA, and CDC42 1404:1438 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 9 33 theme small 1404:1408 arg1 RhoA 1424:1427 RhoA 1424:1427 RhoA 1424:1427 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 9 33 theme small 1404:1408 arg1 CDC42 1434:1438 CDC42 1434:1438 CDC42 1434:1438 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 9 34 contain had 1514:1516 arg1 inhibitors 1486:1495 selective chemical inhibitors 1467:1495 selective chemical inhibitors of these GTPases 1467:1512 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 9 34 contain had 1514:1516 arg2 effect 1521:1526 no effect 1518:1526 no effect 1518:1526 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 10 35 theme GTPase 1724:1729 arg1 targeting 1700:1708 the targeting 1696:1708 the targeting of an unknown GTPase 1696:1729 By contrast, the broad GTPase agonist ML099 countered the effects of 6-TG, suggesting that the antiviral activity of 6-TG requires the targeting of an unknown GTPase. 36121863 6 36 from deficient 901:909 arg1 Spike 914:918 Spike 914:918 Spike 914:918 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 3 37 theme proteins 445:452 arg1 accumulation 371:382 accumulation 371:382 accumulation of full-length viral genomes, subgenomic RNAs and structural proteins 371:452 6-Thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. 36121863 0 38 theme Spike 32:36 arg1 processing 46:55 coronavirus Spike protein processing 20:55 coronavirus Spike protein processing 20:55 Thiopurines inhibit coronavirus Spike protein processing and incorporation into progeny virions. 36121863 5 39 theme 6-TG-treated 733:744 arg1 cells 746:750 6-TG-treated cells 733:750 6-TG-treated cells 733:750 SARS-CoV-2 virus-like particles (VLPs) harvested from 6-TG-treated cells were deficient in Spike. 36121863 10 40 theme 6-TG 1682:1685 arg1 activity 1670:1677 the antiviral activity 1656:1677 the antiviral activity of 6-TG 1656:1685 By contrast, the broad GTPase agonist ML099 countered the effects of 6-TG, suggesting that the antiviral activity of 6-TG requires the targeting of an unknown GTPase. 36121863 8 41 theme antiviral 1337:1345 arg1 activity 1347:1354 antiviral activity 1337:1354 antiviral activity 1337:1354 Using biochemical and genetic approaches we demonstrated that 6-TG is a pro-drug that must be converted to the nucleotide form by hypoxanthine phosphoribosyltransferase 1 (HPRT1) to achieve antiviral activity. 36121863 3 42 theme full-length 387:397 arg1 genomes 405:411 full-length viral genomes 387:411 full-length viral genomes 387:411 6-Thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. 36121863 4 43 theme expression 466:475 arg1 models 477:482 ectopic expression models 458:482 ectopic expression models 458:482 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 1 44 theme outstanding 109:119 arg1 need 121:124 an outstanding need 106:124 an outstanding need for broadly acting antiviral drugs to combat emerging viral diseases 106:193 There is an outstanding need for broadly acting antiviral drugs to combat emerging viral diseases. 36121863 3 45 theme RNAs 425:428 arg1 accumulation 371:382 accumulation 371:382 accumulation of full-length viral genomes, subgenomic RNAs and structural proteins 371:452 6-Thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. 36121863 8 46 theme genetic 1169:1175 arg1 approaches 1177:1186 biochemical and genetic approaches 1153:1186 biochemical and genetic approaches 1153:1186 Using biochemical and genetic approaches we demonstrated that 6-TG is a pro-drug that must be converted to the nucleotide form by hypoxanthine phosphoribosyltransferase 1 (HPRT1) to achieve antiviral activity. 36121863 4 47 theme ectopic 458:464 arg1 models 477:482 ectopic expression models 458:482 ectopic expression models 458:482 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 4 48 from Spike 663:667 arg1 removal 621:627 enzymatic removal 611:627 enzymatic removal of N-linked oligosaccharides from Spike 611:667 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 4 48 from Spike 663:667 arg1 oligosaccharides 641:656 N-linked oligosaccharides 632:656 N-linked oligosaccharides from Spike 632:667 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 7 49 from models 1041:1046 arg1 findings 980:987 these findings 974:987 these findings from complementary ectopic expression and infection models 974:1046 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 0 50 theme protein 38:44 arg1 processing 46:55 coronavirus Spike protein processing 20:55 coronavirus Spike protein processing 20:55 Thiopurines inhibit coronavirus Spike protein processing and incorporation into progeny virions. 36121863 4 51 theme Spike 549:553 arg1 mobility 537:544 the electrophoretic mobility 517:544 the electrophoretic mobility of Spike 517:553 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 7 52 theme 6-TG 1131:1134 arg1 treatment 1136:1144 6-TG treatment 1131:1144 6-TG treatment 1131:1144 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 4 53 link N-linked 632:639 arg1 oligosaccharides 641:656 N-linked oligosaccharides 632:656 N-linked oligosaccharides from Spike 632:667 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 10 54 theme 6-TG 1634:1637 arg1 effects 1623:1629 the effects 1619:1629 the effects of 6-TG 1619:1637 By contrast, the broad GTPase agonist ML099 countered the effects of 6-TG, suggesting that the antiviral activity of 6-TG requires the targeting of an unknown GTPase. 36121863 6 55 theme similar 798:804 arg1 effect 806:811 a similar effect 796:811 a similar effect 796:811 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 5 56 from Spike 770:774 arg1 deficient 757:765 deficient 757:765 deficient 757:765 SARS-CoV-2 virus-like particles (VLPs) harvested from 6-TG-treated cells were deficient in Spike. 36121863 9 57 theme Spike 1531:1535 arg1 processing 1537:1546 Spike processing 1531:1546 Spike processing 1531:1546 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 3 58 theme subgenomic 414:423 arg1 RNAs 425:428 subgenomic RNAs 414:428 subgenomic RNAs 414:428 6-Thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. 36121863 4 59 theme diverse 560:566 arg1 betacoronaviruses 568:584 diverse betacoronaviruses 560:584 diverse betacoronaviruses 560:584 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 7 60 theme treatment 1136:1144 arg1 processing 1103:1112 processing 1103:1112 processing 1103:1112 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 7 60 theme treatment 1136:1144 arg1 outcome 1120:1126 an outcome 1117:1126 an outcome of 6-TG treatment 1117:1144 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 7 60 theme treatment 1136:1144 arg1 trafficking 1087:1097 defective Spike trafficking 1071:1097 defective Spike trafficking 1071:1097 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 7 61 theme defective 1071:1079 arg1 processing 1103:1112 processing 1103:1112 processing 1103:1112 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 7 61 theme defective 1071:1079 arg1 outcome 1120:1126 an outcome 1117:1126 an outcome of 6-TG treatment 1117:1144 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 7 61 theme defective 1071:1079 arg1 trafficking 1087:1097 defective Spike trafficking 1071:1097 defective Spike trafficking 1071:1097 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 8 62 theme nucleotide 1258:1267 arg1 form 1269:1272 the nucleotide form 1254:1272 the nucleotide form 1254:1272 Using biochemical and genetic approaches we demonstrated that 6-TG is a pro-drug that must be converted to the nucleotide form by hypoxanthine phosphoribosyltransferase 1 (HPRT1) to achieve antiviral activity. 36121863 2 63 theme betacoronaviruses 260:276 arg1 replication 241:251 the replication 237:251 the replication of the betacoronaviruses HCoV-OC43 and SARS-CoV-2 237:301 Here, we report that thiopurines inhibit the replication of the betacoronaviruses HCoV-OC43 and SARS-CoV-2. 36121863 7 64 theme Spike 1081:1085 arg1 processing 1103:1112 processing 1103:1112 processing 1103:1112 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 7 64 theme Spike 1081:1085 arg1 outcome 1120:1126 an outcome 1117:1126 an outcome of 6-TG treatment 1117:1144 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 7 64 theme Spike 1081:1085 arg1 trafficking 1087:1097 defective Spike trafficking 1071:1097 defective Spike trafficking 1071:1097 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 6 65 from Spike 914:918 arg1 deficient 901:909 deficient 901:909 deficient 901:909 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 4 66 theme N-linked 632:639 arg1 oligosaccharides 641:656 N-linked oligosaccharides 632:656 N-linked oligosaccharides from Spike 632:667 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36121863 9 67 theme GTPases 1506:1512 arg1 inhibitors 1486:1495 selective chemical inhibitors 1467:1495 selective chemical inhibitors of these GTPases 1467:1512 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 6 68 theme 6-TG 777:780 arg1 treatment 782:790 6-TG treatment 777:790 6-TG treatment 777:790 6-TG treatment had a similar effect on production of lentiviruses pseudotyped with SARS-CoV-2 Spike, yielding pseudoviruses deficient in Spike and unable to infect ACE2-expressing cells. 36121863 1 69 theme acting 138:143 arg1 drugs 155:159 broadly acting antiviral drugs 130:159 broadly acting antiviral drugs 130:159 There is an outstanding need for broadly acting antiviral drugs to combat emerging viral diseases. 36121863 11 70 theme promising 1787:1795 arg1 GTPases 1775:1781 small GTPases 1769:1781 small GTPases 1769:1781 Overall, these findings suggest that small GTPases are promising targets for host-targeted antivirals. 36121863 11 70 theme promising 1787:1795 arg1 targets 1797:1803 promising targets 1787:1803 promising targets for host-targeted antivirals 1787:1832 Overall, these findings suggest that small GTPases are promising targets for host-targeted antivirals. 36121863 0 71 theme progeny 80:86 arg1 virions 88:94 progeny virions 80:94 progeny virions 80:94 Thiopurines inhibit coronavirus Spike protein processing and incorporation into progeny virions. 36121863 10 72 theme unknown 1716:1722 arg1 GTPase 1724:1729 an unknown GTPase 1713:1729 an unknown GTPase 1713:1729 By contrast, the broad GTPase agonist ML099 countered the effects of 6-TG, suggesting that the antiviral activity of 6-TG requires the targeting of an unknown GTPase. 36121863 1 73 theme antiviral 145:153 arg1 drugs 155:159 broadly acting antiviral drugs 130:159 broadly acting antiviral drugs 130:159 There is an outstanding need for broadly acting antiviral drugs to combat emerging viral diseases. 36121863 11 74 theme small 1769:1773 arg1 GTPases 1775:1781 small GTPases 1769:1781 small GTPases 1769:1781 Overall, these findings suggest that small GTPases are promising targets for host-targeted antivirals. 36121863 11 74 theme small 1769:1773 arg1 targets 1797:1803 promising targets 1787:1803 promising targets for host-targeted antivirals 1787:1832 Overall, these findings suggest that small GTPases are promising targets for host-targeted antivirals. 36121863 9 75 theme selective 1467:1475 arg1 inhibitors 1486:1495 selective chemical inhibitors 1467:1495 selective chemical inhibitors of these GTPases 1467:1512 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 0 76 theme coronavirus 20:30 arg1 processing 46:55 coronavirus Spike protein processing 20:55 coronavirus Spike protein processing 20:55 Thiopurines inhibit coronavirus Spike protein processing and incorporation into progeny virions. 36121863 9 77 dep GTPases 1410:1416 arg1 Rac1 1418:1421 Rac1 1418:1421 Rac1 1418:1421 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 9 77 dep GTPases 1410:1416 arg1 GTPases 1410:1416 small GTPases Rac1, RhoA, and CDC42 1404:1438 small GTPases Rac1, RhoA, and CDC42 1404:1438 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 9 77 dep GTPases 1410:1416 arg1 RhoA 1424:1427 RhoA 1424:1427 RhoA 1424:1427 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 9 77 dep GTPases 1410:1416 arg1 CDC42 1434:1438 CDC42 1434:1438 CDC42 1434:1438 This nucleotide form has been shown to inhibit small GTPases Rac1, RhoA, and CDC42; however, we observed that selective chemical inhibitors of these GTPases had no effect on Spike processing or accumulation. 36121863 7 78 from expression 1016:1025 arg1 findings 980:987 these findings 974:987 these findings from complementary ectopic expression and infection models 974:1046 Together, these findings from complementary ectopic expression and infection models strongly indicate that defective Spike trafficking and processing is an outcome of 6-TG treatment. 36121863 10 79 theme antiviral 1660:1668 arg1 activity 1670:1677 the antiviral activity 1656:1677 the antiviral activity of 6-TG 1656:1685 By contrast, the broad GTPase agonist ML099 countered the effects of 6-TG, suggesting that the antiviral activity of 6-TG requires the targeting of an unknown GTPase. 36121863 4 80 theme oligosaccharides 641:656 arg1 removal 621:627 enzymatic removal 611:627 enzymatic removal of N-linked oligosaccharides from Spike 611:667 In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching the effects of enzymatic removal of N-linked oligosaccharides from Spike in vitro. 36607620 4 0 theme 2D 846:847 arg1 experiments 856:866 one-dimensional long-range and 2D J-HMBC experiments 815:866 one-dimensional long-range and 2D J-HMBC experiments 815:866 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 8 1 theme underlying 1987:1996 arg1 forces 2007:2012 the underlying physical forces 1983:2012 the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field 1983:2115 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 7 2 theme inter-glycosidic 1552:1567 arg1 distances 1583:1591 inter-glycosidic proton-proton distances 1552:1591 inter-glycosidic proton-proton distances 1552:1591 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 7 3 theme conformational 1512:1525 arg1 space 1527:1531 conformational space 1512:1531 conformational space 1512:1531 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 4 4 theme NMR 605:607 arg1 experiments 609:619 Translational diffusion NMR experiments 581:619 Translational diffusion NMR experiments 581:619 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 1 5 gly glycoproteins 212:224 arg1 glycoproteins 212:224 N-linked glycoproteins 203:224 N-linked glycoproteins from viruses and mammals 203:249 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 0 6 theme Glycosidic 0:9 arg1 disaccharides 34:46 Glycosidic α-linked mannopyranose disaccharides 0:46 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 0:162 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 4 7 theme long-range 831:840 arg1 experiments 856:866 one-dimensional long-range and 2D J-HMBC experiments 815:866 one-dimensional long-range and 2D J-HMBC experiments 815:866 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 1 8 from bacteria 296:303 arg1 polysaccharides 265:279 polysaccharides 265:279 polysaccharides from fungi and bacteria 265:303 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 8 from bacteria 296:303 arg1 component 190:198 a structural component 177:198 a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria 177:303 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 8 from bacteria 296:303 arg1 D-Mannose 164:172 D-Mannose 164:172 D-Mannose 164:172 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 3 9 theme mannose-containing 482:499 arg1 disaccharides 501:513 mannose-containing disaccharides 482:513 mannose-containing disaccharides 482:513 As models for these oligo- and polysaccharides, a series of mannose-containing disaccharides have been investigated with respect to conformation and dynamics. 36607620 1 10 theme N-linked 203:210 arg1 glycoproteins 212:224 N-linked glycoproteins 203:224 N-linked glycoproteins from viruses and mammals 203:249 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 6 11 theme force 1397:1401 arg1 fields 1403:1408 the additive CHARMM36 and Drude polarizable force fields 1353:1408 the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions 1353:1484 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 4 12 theme dependent 925:933 arg1 constants 958:966 conformationally dependent heteronuclear coupling constants 908:966 conformationally dependent heteronuclear coupling constants across glycosidic linkages 908:993 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 4 13 theme Translational 581:593 arg1 experiments 609:619 Translational diffusion NMR experiments 581:619 Translational diffusion NMR experiments 581:619 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 0 14 theme force 150:154 arg1 fields 156:161 additive and Drude polarizable force fields 119:161 additive and Drude polarizable force fields 119:161 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 1 15 from viruses 231:237 arg1 D-Mannose 164:172 D-Mannose 164:172 D-Mannose 164:172 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 15 from viruses 231:237 arg1 component 190:198 a structural component 177:198 a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria 177:303 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 15 from viruses 231:237 arg1 glycoproteins 212:224 N-linked glycoproteins 203:224 N-linked glycoproteins from viruses and mammals 203:249 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 16 from mammals 243:249 arg1 D-Mannose 164:172 D-Mannose 164:172 D-Mannose 164:172 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 16 from mammals 243:249 arg1 component 190:198 a structural component 177:198 a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria 177:303 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 16 from mammals 243:249 arg1 glycoproteins 212:224 N-linked glycoproteins 203:224 N-linked glycoproteins from viruses and mammals 203:249 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 6 17 theme CHARMM36 1366:1373 arg1 fields 1403:1408 the additive CHARMM36 and Drude polarizable force fields 1353:1408 the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions 1353:1484 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 5 18 theme labeled 1057:1063 arg1 -α-D-Manp-OMe 1089:1101 the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe 1034:1101 the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe 1034:1101 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 8 19 theme radial 1895:1900 arg1 functions 1915:1923 radial distribution functions 1895:1923 radial distribution functions 1895:1923 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 7 20 theme coupling 1722:1729 arg1 constants 1731:1739 conformationally dependent NMR scalar coupling constants 1684:1739 conformationally dependent NMR scalar coupling constants 1684:1739 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 8 21 theme C36 2101:2103 arg1 field 2111:2115 the Drude polarizable versus additive C36 force field 2063:2115 the Drude polarizable versus additive C36 force field 2063:2115 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 8 22 theme functions 1915:1923 arg1 analyses 1864:1871 analyses 1864:1871 analyses of dipole moments and radial distribution functions with water of the hydroxyl groups 1864:1957 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 7 23 theme NMR 1711:1713 arg1 constants 1731:1739 conformationally dependent NMR scalar coupling constants 1684:1739 conformationally dependent NMR scalar coupling constants 1684:1739 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 6 24 theme Molecular 1246:1254 arg1 simulations 1265:1275 Molecular dynamics simulations 1246:1275 Molecular dynamics simulations 1246:1275 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 6 24 theme Molecular 1246:1254 arg1 solvent 1339:1345 solvent 1339:1345 solvent 1339:1345 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 5 25 theme conformational 1140:1153 arg1 analysis 1155:1162 conformational analysis 1140:1162 conformational analysis 1140:1162 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 8 26 theme model 2176:2180 arg1 utility 2143:2149 the improved utility 2130:2149 the improved utility of the Drude polarizable model in investigating complex carbohydrates 2130:2219 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 4 27 theme rotational 646:655 arg1 times 669:673 rotational correlation times 646:673 rotational correlation times for the molecules 646:691 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 0 28 theme dynamics 83:90 arg1 study 103:107 an NMR spectroscopy and molecular dynamics simulation study 49:107 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 0:162 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 8 29 with analyses 1864:1871 arg1 water 1930:1934 water 1930:1934 water of the hydroxyl groups 1930:1957 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 4 30 theme coupling 949:956 arg1 constants 958:966 conformationally dependent heteronuclear coupling constants 908:966 conformationally dependent heteronuclear coupling constants across glycosidic linkages 908:993 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 1 31 from fungi 286:290 arg1 polysaccharides 265:279 polysaccharides 265:279 polysaccharides from fungi and bacteria 265:303 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 31 from fungi 286:290 arg1 component 190:198 a structural component 177:198 a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria 177:303 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 31 from fungi 286:290 arg1 D-Mannose 164:172 D-Mannose 164:172 D-Mannose 164:172 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 4 32 theme 1D 713:714 arg1 experiments 734:744 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments 694:744 experiments 734:744 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 8 33 theme improved 2134:2141 arg1 utility 2143:2149 the improved utility 2130:2149 the improved utility of the Drude polarizable model in investigating complex carbohydrates 2130:2219 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 8 34 theme groups 1952:1957 arg1 water 1930:1934 water 1930:1934 water of the hydroxyl groups 1930:1957 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 4 35 theme NMR 730:732 arg1 experiments 734:744 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments 694:744 experiments 734:744 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 0 36 theme additive 119:126 arg1 fields 156:161 additive and Drude polarizable force fields 119:161 additive and Drude polarizable force fields 119:161 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 7 37 theme root-mean-square 1800:1815 arg1 differences 1817:1827 closely similar root-mean-square differences 1784:1827 closely similar root-mean-square differences for the two force fields 1784:1852 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 0 38 theme molecular 73:81 arg1 dynamics 83:90 molecular dynamics 73:90 molecular dynamics 73:90 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 8 39 theme Drude 2158:2162 arg1 model 2176:2180 the Drude polarizable model 2154:2180 the Drude polarizable model 2154:2180 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 8 40 theme wider 2028:2032 arg1 sampling 2049:2056 the wider conformational sampling 2024:2056 the wider conformational sampling with the Drude polarizable versus additive C36 force field 2024:2115 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 0 41 theme mannopyranose 20:32 arg1 disaccharides 34:46 Glycosidic α-linked mannopyranose disaccharides 0:46 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 0:162 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 5 42 theme Karplus-type 1218:1229 arg1 relationships 1231:1243 Karplus-type relationships 1218:1243 Karplus-type relationships 1218:1243 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 5 43 theme 13C,13C 1173:1179 arg1 constants 1190:1198 13C,13C coupling constants 1173:1198 13C,13C coupling constants 1173:1198 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 7 44 located observed 1656:1663 arg2 deviations 1640:1649 deviations 1640:1649 deviations 1640:1649 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 7 44 located observed 1656:1663 arg1 cases 1634:1638 some cases 1629:1638 some cases 1629:1638 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 5 45 dep facilitating 1127:1138 arg1 based 1164:1168 based 1164:1168 based on 13C,13C coupling constants as interpreted by Karplus-type relationships 1164:1243 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 4 46 theme proton-proton 787:799 arg1 distances 801:809 inter-residue proton-proton distances 773:809 inter-residue proton-proton distances 773:809 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 6 47 theme population 1461:1470 arg1 distributions 1472:1484 broader population distributions 1453:1484 broader population distributions 1453:1484 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 5 48 theme 13C-isotope 1045:1055 arg1 -α-D-Manp-OMe 1089:1101 the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe 1034:1101 the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe 1034:1101 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 5 49 theme further 1006:1012 arg1 data 1028:1031 further spectroscopic data 1006:1031 further spectroscopic data 1006:1031 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 7 50 theme proton-proton 1569:1581 arg1 distances 1583:1591 inter-glycosidic proton-proton distances 1552:1591 inter-glycosidic proton-proton distances 1552:1591 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 8 51 theme physical 1998:2005 arg1 forces 2007:2012 the underlying physical forces 1983:2012 the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field 1983:2115 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 2 52 theme Structural 306:315 arg1 components 317:326 Structural components 306:326 Structural components 306:326 Structural components often consist of D-Manp residues joined via α-(1→2)-, α-(1→3)-, α-(1→4)- or α-(1→6)-linkages. 36607620 4 53 theme J-HMBC 849:854 arg1 experiments 856:866 one-dimensional long-range and 2D J-HMBC experiments 815:866 one-dimensional long-range and 2D J-HMBC experiments 815:866 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 0 54 link α-linked 11:18 arg1 disaccharides 34:46 Glycosidic α-linked mannopyranose disaccharides 0:46 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 0:162 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 8 55 from differences 1968:1978 arg1 forces 2007:2012 the underlying physical forces 1983:2012 the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field 1983:2115 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 6 56 theme explicit 1321:1328 arg1 water 1330:1334 explicit water 1321:1334 explicit water 1321:1334 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 1 57 theme structural 179:188 arg1 D-Mannose 164:172 D-Mannose 164:172 D-Mannose 164:172 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 57 theme structural 179:188 arg1 component 190:198 a structural component 177:198 a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria 177:303 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 0 58 theme NMR 52:54 arg1 spectroscopy 56:67 NMR spectroscopy 52:67 NMR spectroscopy 52:67 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 4 59 theme diffusion 595:603 arg1 experiments 609:619 Translational diffusion NMR experiments 581:619 Translational diffusion NMR experiments 581:619 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 8 60 theme conformational 2034:2047 arg1 sampling 2049:2056 the wider conformational sampling 2024:2056 the wider conformational sampling with the Drude polarizable versus additive C36 force field 2024:2115 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 4 61 theme one-dimensional 815:829 arg1 experiments 856:866 one-dimensional long-range and 2D J-HMBC experiments 815:866 one-dimensional long-range and 2D J-HMBC experiments 815:866 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 0 62 theme polarizable 138:148 arg1 fields 156:161 additive and Drude polarizable force fields 119:161 additive and Drude polarizable force fields 119:161 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 6 63 theme polarizable 1385:1395 arg1 force 1397:1401 Drude polarizable force 1379:1401 Drude polarizable force 1379:1401 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 8 64 theme additive 2092:2099 arg1 field 2111:2115 the Drude polarizable versus additive C36 force field 2063:2115 the Drude polarizable versus additive C36 force field 2063:2115 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 3 65 theme disaccharides 501:513 arg1 series 472:477 a series 470:477 a series of mannose-containing disaccharides 470:513 As models for these oligo- and polysaccharides, a series of mannose-containing disaccharides have been investigated with respect to conformation and dynamics. 36607620 3 65 theme disaccharides 501:513 arg1 models 425:430 models 425:430 models for these oligo- and polysaccharides 425:467 As models for these oligo- and polysaccharides, a series of mannose-containing disaccharides have been investigated with respect to conformation and dynamics. 36607620 8 66 theme dipole 1876:1881 arg1 moments 1883:1889 dipole moments 1876:1889 dipole moments 1876:1889 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 3 67 dep oligo- 442:447 arg1 these 436:440 these 436:440 these 436:440 As models for these oligo- and polysaccharides, a series of mannose-containing disaccharides have been investigated with respect to conformation and dynamics. 36607620 7 68 theme scalar 1715:1720 arg1 constants 1731:1739 conformationally dependent NMR scalar coupling constants 1684:1739 conformationally dependent NMR scalar coupling constants 1684:1739 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 4 69 theme correlation 657:667 arg1 times 669:673 rotational correlation times 646:673 rotational correlation times for the molecules 646:691 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 6 70 theme additive 1357:1364 arg1 CHARMM36 1366:1373 the additive CHARMM36 1353:1373 the additive CHARMM36 1353:1373 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 5 71 theme α-D-[1,2-13C2 1065:1077 arg1 -α-D-Manp-OMe 1089:1101 the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe 1034:1101 the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe 1034:1101 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 8 72 theme force 2105:2109 arg1 field 2111:2115 the Drude polarizable versus additive C36 force field 2063:2115 the Drude polarizable versus additive C36 force field 2063:2115 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 7 73 theme dependent 1701:1709 arg1 constants 1731:1739 conformationally dependent NMR scalar coupling constants 1684:1739 conformationally dependent NMR scalar coupling constants 1684:1739 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 6 74 theme dynamics 1256:1263 arg1 simulations 1265:1275 Molecular dynamics simulations 1246:1275 Molecular dynamics simulations 1246:1275 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 6 74 theme dynamics 1256:1263 arg1 solvent 1339:1345 solvent 1339:1345 solvent 1339:1345 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 6 75 theme broader 1453:1459 arg1 distributions 1472:1484 broader population distributions 1453:1484 broader population distributions 1453:1484 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 5 76 theme Manp- 1079:1083 arg1 -α-D-Manp-OMe 1089:1101 the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe 1034:1101 the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe 1034:1101 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 8 77 theme distribution 1902:1913 arg1 functions 1915:1923 radial distribution functions 1895:1923 radial distribution functions 1895:1923 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 7 78 theme calculated 1673:1682 arg1 constants 1731:1739 conformationally dependent NMR scalar coupling constants 1684:1739 conformationally dependent NMR scalar coupling constants 1684:1739 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 4 79 theme glycosidic 975:984 arg1 linkages 986:993 glycosidic linkages 975:993 glycosidic linkages 975:993 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 0 80 theme simulation 92:101 arg1 study 103:107 an NMR spectroscopy and molecular dynamics simulation study 49:107 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 0:162 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 1 81 from component 190:198 arg1 mammals 243:249 mammals 243:249 mammals 243:249 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 81 from component 190:198 arg1 bacteria 296:303 bacteria 296:303 bacteria 296:303 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 81 from component 190:198 arg1 glycoproteins 212:224 N-linked glycoproteins 203:224 N-linked glycoproteins from viruses and mammals 203:249 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 81 from component 190:198 arg1 viruses 231:237 viruses 231:237 viruses 231:237 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 81 from component 190:198 arg1 polysaccharides 265:279 polysaccharides 265:279 polysaccharides from fungi and bacteria 265:303 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 1 81 from component 190:198 arg1 fungi 286:290 fungi 286:290 fungi 286:290 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 2 82 theme 1→6 407:409 arg1 -linkages 411:419 α-(1→6)-linkages 404:419 α-(1→6)-linkages 404:419 Structural components often consist of D-Manp residues joined via α-(1→2)-, α-(1→3)-, α-(1→4)- or α-(1→6)-linkages. 36607620 7 83 theme force 1841:1845 arg1 fields 1847:1852 the two force fields 1833:1852 the two force fields 1833:1852 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 4 84 theme heteronuclear 935:947 arg1 constants 958:966 conformationally dependent heteronuclear coupling constants 908:966 conformationally dependent heteronuclear coupling constants across glycosidic linkages 908:993 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 8 85 theme hydroxyl 1943:1950 arg1 groups 1952:1957 the hydroxyl groups 1939:1957 the hydroxyl groups 1939:1957 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 1 86 link N-linked 203:210 arg1 glycoproteins 212:224 N-linked glycoproteins 203:224 N-linked glycoproteins from viruses and mammals 203:249 D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. 36607620 4 87 theme 1H,1H-T-ROESY 716:728 arg1 experiments 734:744 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments 694:744 experiments 734:744 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 0 88 theme α-linked 11:18 arg1 disaccharides 34:46 Glycosidic α-linked mannopyranose disaccharides 0:46 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 0:162 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 8 89 theme polarizable 2073:2083 arg1 field 2111:2115 the Drude polarizable versus additive C36 force field 2063:2115 the Drude polarizable versus additive C36 force field 2063:2115 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 8 90 with sampling 2049:2056 arg1 field 2111:2115 the Drude polarizable versus additive C36 force field 2063:2115 the Drude polarizable versus additive C36 force field 2063:2115 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 7 91 theme similar 1792:1798 arg1 differences 1817:1827 closely similar root-mean-square differences 1784:1827 closely similar root-mean-square differences for the two force fields 1784:1852 Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. 36607620 4 92 theme 1D 694:695 arg1 1H,1H-NOESY 697:707 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments 694:744 1H,1H-NOESY 697:707 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 8 93 theme complex 2199:2205 arg1 carbohydrates 2207:2219 complex carbohydrates 2199:2219 complex carbohydrates 2199:2219 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 2 94 theme α- 404:405 arg1 -linkages 411:419 α-(1→6)-linkages 404:419 α-(1→6)-linkages 404:419 Structural components often consist of D-Manp residues joined via α-(1→2)-, α-(1→3)-, α-(1→4)- or α-(1→6)-linkages. 36607620 0 95 theme spectroscopy 56:67 arg1 study 103:107 an NMR spectroscopy and molecular dynamics simulation study 49:107 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 0:162 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 5 96 theme coupling 1181:1188 arg1 constants 1190:1198 13C,13C coupling constants 1173:1198 13C,13C coupling constants 1173:1198 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 6 97 theme Drude 1379:1383 arg1 force 1397:1401 Drude polarizable force 1379:1401 Drude polarizable force 1379:1401 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36607620 4 98 theme inter-residue 773:785 arg1 distances 801:809 inter-residue proton-proton distances 773:809 inter-residue proton-proton distances 773:809 Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. 36607620 0 99 dep disaccharides 34:46 arg1 study 103:107 an NMR spectroscopy and molecular dynamics simulation study 49:107 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 0:162 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 8 100 theme moments 1883:1889 arg1 analyses 1864:1871 analyses 1864:1871 analyses of dipole moments and radial distribution functions with water of the hydroxyl groups 1864:1957 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 2 101 theme D-Manp 345:350 arg1 residues 352:359 D-Manp residues 345:359 D-Manp residues joined via α-(1→2)-, α-(1→3)-, α-(1→4)- or α-(1→6)-linkages 345:419 Structural components often consist of D-Manp residues joined via α-(1→2)-, α-(1→3)-, α-(1→4)- or α-(1→6)-linkages. 36607620 5 102 theme spectroscopic 1014:1026 arg1 data 1028:1031 further spectroscopic data 1006:1031 further spectroscopic data 1006:1031 To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. 36607620 0 103 theme Drude 132:136 arg1 fields 156:161 additive and Drude polarizable force fields 119:161 additive and Drude polarizable force fields 119:161 Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields. 36607620 8 104 theme polarizable 2164:2174 arg1 model 2176:2180 the Drude polarizable model 2154:2180 the Drude polarizable model 2154:2180 However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates. 36607620 6 105 with disaccharides 1302:1314 arg1 water 1330:1334 explicit water 1321:1334 explicit water 1321:1334 Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. 36787362 5 0 theme potential 766:774 arg1 role 776:779 a potential role 764:779 a potential role in nascent protein processing 764:809 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 7 1 theme plasma 1018:1023 arg1 proteins 1034:1041 sperm plasma membrane proteins 1012:1041 sperm plasma membrane proteins 1012:1041 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 7 2 theme acrosomal 1080:1088 arg1 proteins 1099:1106 multiple acrosomal membrane proteins 1071:1106 multiple acrosomal membrane proteins involved in fertilization 1071:1132 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 1 3 theme essential 235:243 arg1 roles 245:249 essential roles 235:249 essential roles 235:249 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 0 4 theme sperm-egg 88:96 arg1 interaction 98:108 sperm-egg interaction 88:108 sperm-egg interaction 88:108 1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm-egg interaction. 36787362 5 5 theme N-linked 654:661 arg1 glycosylation 663:675 N-linked glycosylation 654:675 N-linked glycosylation 654:675 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 5 6 theme -Golgi 733:738 arg1 trafficking 740:750 endoplasmic reticulum (ER)-Golgi trafficking 707:750 endoplasmic reticulum (ER)-Golgi trafficking 707:750 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 8 7 theme upregulated 1159:1169 arg1 chaperones 1171:1180 upregulated chaperones 1159:1180 upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination 1159:1260 The knockout sperm show upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination; strikingly, SPACA6 becomes undetectable. 36787362 1 8 theme mammalian 254:262 arg1 binding 271:277 mammalian gamete binding 254:277 mammalian gamete binding 254:277 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 8 9 theme elevated 1230:1237 arg1 ubiquitination 1247:1260 elevated protein ubiquitination 1230:1260 elevated protein ubiquitination 1230:1260 The knockout sperm show upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination; strikingly, SPACA6 becomes undetectable. 36787362 6 10 theme complex 917:923 arg1 subunits 869:876 non-catalytic subunits 855:876 non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for N-glycosylation 855:960 The ablation of 1700029I15Rik destabilizes non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for N-glycosylation. 36787362 7 11 theme normal 991:996 arg1 expression 998:1007 normal expression 991:1007 normal expression of sperm plasma membrane proteins 991:1041 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 9 12 theme acrosomal 1404:1412 arg1 proteins 1423:1430 acrosomal membrane proteins 1404:1430 acrosomal membrane proteins 1404:1430 Our results support for a specific, 1700029I15Rik-mediated pathway underpinning the biosynthesis of acrosomal membrane proteins during spermiogenesis. 36787362 0 13 theme acrosomal 47:55 arg1 proteins 66:73 acrosomal membrane proteins 47:73 acrosomal membrane proteins required for sperm-egg interaction 47:108 1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm-egg interaction. 36787362 7 14 theme knockout 967:974 arg1 testes 976:981 The knockout testes 963:981 The knockout testes 963:981 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 9 15 theme membrane 1414:1421 arg1 proteins 1423:1430 acrosomal membrane proteins 1404:1430 acrosomal membrane proteins 1404:1430 Our results support for a specific, 1700029I15Rik-mediated pathway underpinning the biosynthesis of acrosomal membrane proteins during spermiogenesis. 36787362 9 16 theme proteins 1423:1430 arg1 biosynthesis 1388:1399 the biosynthesis 1384:1399 the biosynthesis of acrosomal membrane proteins during spermiogenesis 1384:1452 Our results support for a specific, 1700029I15Rik-mediated pathway underpinning the biosynthesis of acrosomal membrane proteins during spermiogenesis. 36787362 3 17 theme male 420:423 arg1 mice 425:428 1700029I15Rik knockout male mice 397:428 1700029I15Rik knockout male mice 397:428 Here, we show that 1700029I15Rik knockout male mice are severely subfertile and their spermatozoa do not fuse with eggs. 36787362 8 18 theme protein 1239:1245 arg1 ubiquitination 1247:1260 elevated protein ubiquitination 1230:1260 elevated protein ubiquitination 1230:1260 The knockout sperm show upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination; strikingly, SPACA6 becomes undetectable. 36787362 1 19 theme gamete 264:269 arg1 binding 271:277 mammalian gamete binding 254:277 mammalian gamete binding 254:277 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 20 theme Sperm 111:115 arg1 acrosome-associated 198:216 sperm acrosome-associated 6 192:218 sperm acrosome-associated 6 (SPACA6) 192:227 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 20 theme Sperm 111:115 arg1 proteins 136:143 Sperm acrosomal membrane proteins 111:143 Sperm acrosomal membrane proteins 111:143 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 20 theme Sperm 111:115 arg1 fusion 170:175 Izumo sperm-egg fusion 1 154:177 Izumo sperm-egg fusion 1 (IZUMO1) 154:186 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 5 21 theme endoplasmic 707:717 arg1 reticulum 719:727 endoplasmic reticulum 707:727 endoplasmic reticulum (ER)-Golgi trafficking 707:750 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 5 21 theme endoplasmic 707:717 arg1 ER 730:731 ER 730:731 ER 730:731 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 1 22 theme acrosomal 117:125 arg1 acrosome-associated 198:216 sperm acrosome-associated 6 192:218 sperm acrosome-associated 6 (SPACA6) 192:227 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 22 theme acrosomal 117:125 arg1 proteins 136:143 Sperm acrosomal membrane proteins 111:143 Sperm acrosomal membrane proteins 111:143 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 22 theme acrosomal 117:125 arg1 fusion 170:175 Izumo sperm-egg fusion 1 154:177 Izumo sperm-egg fusion 1 (IZUMO1) 154:186 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 23 theme sperm 192:196 arg1 acrosome-associated 198:216 sperm acrosome-associated 6 192:218 sperm acrosome-associated 6 (SPACA6) 192:227 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 23 theme sperm 192:196 arg1 SPACA6 221:226 SPACA6 221:226 SPACA6 221:226 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 4 24 theme round 567:571 arg1 spermatids 573:582 early round spermatids 561:582 early round spermatids 561:582 1700029I15Rik is a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa. 36787362 5 25 theme reticulum 719:727 arg1 trafficking 740:750 endoplasmic reticulum (ER)-Golgi trafficking 707:750 endoplasmic reticulum (ER)-Golgi trafficking 707:750 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 1 26 theme membrane 127:134 arg1 acrosome-associated 198:216 sperm acrosome-associated 6 192:218 sperm acrosome-associated 6 (SPACA6) 192:227 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 26 theme membrane 127:134 arg1 proteins 136:143 Sperm acrosomal membrane proteins 111:143 Sperm acrosomal membrane proteins 111:143 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 26 theme membrane 127:134 arg1 fusion 170:175 Izumo sperm-egg fusion 1 154:177 Izumo sperm-egg fusion 1 (IZUMO1) 154:186 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 3 27 theme 1700029I15Rik 397:409 arg1 mice 425:428 1700029I15Rik knockout male mice 397:428 1700029I15Rik knockout male mice 397:428 Here, we show that 1700029I15Rik knockout male mice are severely subfertile and their spermatozoa do not fuse with eggs. 36787362 4 28 theme early 561:565 arg1 spermatids 573:582 early round spermatids 561:582 early round spermatids 561:582 1700029I15Rik is a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa. 36787362 7 29 theme proteins 1099:1106 arg1 abundance 1058:1066 decreased abundance 1048:1066 decreased abundance of multiple acrosomal membrane proteins involved in fertilization 1048:1132 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 6 30 theme oligosaccharyltransferase 885:909 arg1 complex 917:923 the oligosaccharyltransferase (OST) complex 881:923 the oligosaccharyltransferase (OST) complex that are pivotal for N-glycosylation 881:960 The ablation of 1700029I15Rik destabilizes non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for N-glycosylation. 36787362 6 30 theme oligosaccharyltransferase 885:909 arg1 pivotal 934:940 pivotal 934:940 pivotal 934:940 The ablation of 1700029I15Rik destabilizes non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for N-glycosylation. 36787362 3 31 theme knockout 411:418 arg1 mice 425:428 1700029I15Rik knockout male mice 397:428 1700029I15Rik knockout male mice 397:428 Here, we show that 1700029I15Rik knockout male mice are severely subfertile and their spermatozoa do not fuse with eggs. 36787362 4 32 theme type-II 518:524 arg1 protein 540:546 a type-II transmembrane protein 516:546 a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa 516:612 1700029I15Rik is a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa. 36787362 4 32 theme type-II 518:524 arg1 1700029I15Rik 499:511 1700029I15Rik 499:511 1700029I15Rik 499:511 1700029I15Rik is a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa. 36787362 5 33 theme nascent 784:790 arg1 processing 800:809 nascent protein processing 784:809 nascent protein processing 784:809 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 7 34 theme decreased 1048:1056 arg1 abundance 1058:1066 decreased abundance 1048:1066 decreased abundance of multiple acrosomal membrane proteins involved in fertilization 1048:1132 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 5 35 link N-linked 654:661 arg1 glycosylation 663:675 N-linked glycosylation 654:675 N-linked glycosylation 654:675 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 0 36 theme proteins 66:73 arg1 biosynthesis 31:42 the biosynthesis 27:42 the biosynthesis of acrosomal membrane proteins required for sperm-egg interaction 27:108 1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm-egg interaction. 36787362 5 37 theme disulfide 678:686 arg1 isomerization 688:700 disulfide isomerization 678:700 disulfide isomerization 678:700 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 0 38 theme membrane 57:64 arg1 proteins 66:73 acrosomal membrane proteins 47:73 acrosomal membrane proteins required for sperm-egg interaction 47:108 1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm-egg interaction. 36787362 9 39 dep specific 1330:1337 arg1 1700029I15Rik-mediated 1340:1361 1700029I15Rik-mediated 1340:1361 1700029I15Rik-mediated 1340:1361 Our results support for a specific, 1700029I15Rik-mediated pathway underpinning the biosynthesis of acrosomal membrane proteins during spermiogenesis. 36787362 7 40 theme membrane 1090:1097 arg1 proteins 1099:1106 multiple acrosomal membrane proteins 1071:1106 multiple acrosomal membrane proteins involved in fertilization 1071:1132 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 6 41 theme non-catalytic 855:867 arg1 subunits 869:876 non-catalytic subunits 855:876 non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for N-glycosylation 855:960 The ablation of 1700029I15Rik destabilizes non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for N-glycosylation. 36787362 4 42 theme transmembrane 526:538 arg1 protein 540:546 a type-II transmembrane protein 516:546 a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa 516:612 1700029I15Rik is a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa. 36787362 4 42 theme transmembrane 526:538 arg1 1700029I15Rik 499:511 1700029I15Rik 499:511 1700029I15Rik 499:511 1700029I15Rik is a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa. 36787362 8 43 theme related 1182:1188 arg1 chaperones 1171:1180 upregulated chaperones 1159:1180 upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination 1159:1260 The knockout sperm show upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination; strikingly, SPACA6 becomes undetectable. 36787362 5 44 from role 776:779 arg1 processing 800:809 nascent protein processing 784:809 nascent protein processing 784:809 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 7 45 theme multiple 1071:1078 arg1 proteins 1099:1106 multiple acrosomal membrane proteins 1071:1106 multiple acrosomal membrane proteins involved in fertilization 1071:1132 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 9 46 theme specific 1330:1337 arg1 pathway 1363:1369 a specific, 1700029I15Rik-mediated pathway 1328:1369 a specific, 1700029I15Rik-mediated pathway underpinning the biosynthesis of acrosomal membrane proteins during spermiogenesis 1328:1452 Our results support for a specific, 1700029I15Rik-mediated pathway underpinning the biosynthesis of acrosomal membrane proteins during spermiogenesis. 36787362 7 47 theme membrane 1025:1032 arg1 proteins 1034:1041 sperm plasma membrane proteins 1012:1041 sperm plasma membrane proteins 1012:1041 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 4 48 theme mature 595:600 arg1 spermatozoa 602:612 mature spermatozoa 595:612 mature spermatozoa 595:612 1700029I15Rik is a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa. 36787362 8 49 theme ER-associated 1193:1205 arg1 degradation 1207:1217 ER-associated degradation 1193:1217 ER-associated degradation (ERAD) 1193:1224 The knockout sperm show upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination; strikingly, SPACA6 becomes undetectable. 36787362 8 49 theme ER-associated 1193:1205 arg1 ERAD 1220:1223 ERAD 1220:1223 ERAD 1220:1223 The knockout sperm show upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination; strikingly, SPACA6 becomes undetectable. 36787362 6 50 theme 1700029I15Rik 828:840 arg1 ablation 816:823 The ablation 812:823 The ablation of 1700029I15Rik 812:840 The ablation of 1700029I15Rik destabilizes non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for N-glycosylation. 36787362 7 51 theme proteins 1034:1041 arg1 expression 998:1007 normal expression 991:1007 normal expression of sperm plasma membrane proteins 991:1041 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 1 52 theme Izumo 154:158 arg1 fusion 170:175 Izumo sperm-egg fusion 1 154:177 Izumo sperm-egg fusion 1 (IZUMO1) 154:186 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 52 theme Izumo 154:158 arg1 IZUMO1 180:185 IZUMO1 180:185 IZUMO1 180:185 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 5 53 theme protein 792:798 arg1 processing 800:809 nascent protein processing 784:809 nascent protein processing 784:809 It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. 36787362 7 54 theme sperm 1012:1016 arg1 proteins 1034:1041 sperm plasma membrane proteins 1012:1041 sperm plasma membrane proteins 1012:1041 The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. 36787362 1 55 theme sperm-egg 160:168 arg1 fusion 170:175 Izumo sperm-egg fusion 1 154:177 Izumo sperm-egg fusion 1 (IZUMO1) 154:186 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 1 55 theme sperm-egg 160:168 arg1 IZUMO1 180:185 IZUMO1 180:185 IZUMO1 180:185 Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. 36787362 8 56 theme knockout 1139:1146 arg1 sperm 1148:1152 The knockout sperm 1135:1152 The knockout sperm 1135:1152 The knockout sperm show upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination; strikingly, SPACA6 becomes undetectable. 36349801 4 0 theme lung 806:809 arg1 cancer 811:816 small-cell lung cancer 795:816 small-cell lung cancer [SCLC 795:822 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 6 1 theme salivary 1011:1018 arg1 glycoproteins 1020:1032 their salivary glycoproteins 1005:1032 their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group 1005:1117 Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS. 36349801 1 2 theme late 253:256 arg1 diagnosis 258:266 late diagnosis 253:266 late diagnosis 253:266 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 4 3 theme Bandeiraea 607:616 arg1 Lectin 632:637 Bandeiraea Simplicifolia Lectin I 607:639 Bandeiraea Simplicifolia Lectin I (BS-I) 607:646 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 3 theme Bandeiraea 607:616 arg1 BS-I 642:645 BS-I 642:645 BS-I 642:645 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 10 4 theme galactosylated 1985:1998 arg1 glycans 2009:2015 galactosylated N-linked glycans 1985:2015 galactosylated N-linked glycans associated with LC 1985:2034 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 10 5 link N-linked 2000:2007 arg1 glycans 2009:2015 galactosylated N-linked glycans 1985:2015 galactosylated N-linked glycans associated with LC 1985:2034 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 5 6 from group 903:907 arg1 samples 885:891 Pooled samples 878:891 Pooled samples from each group 878:907 Pooled samples from each group were subsequently validated by the lectin blotting technique. 36349801 4 7 theme volunteers 672:681 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 7 theme volunteers 672:681 arg1 [ADC 749:752 lung adenocarcinoma [ADC]: 39 729:757 lung adenocarcinoma [ADC]: 39 729:757 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 7 theme volunteers 672:681 arg1 [SCLC 818:822 small-cell lung cancer [SCLC 795:822 small-cell lung cancer [SCLC 795:822 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 7 theme volunteers 672:681 arg1 [BPD 718:721 benign pulmonary disease [BPD]: 27 693:726 benign pulmonary disease [BPD]: 27 693:726 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 7 theme volunteers 672:681 arg1 [SCC 784:787 squamous cell carcinoma [SCC]: 28 760:792 squamous cell carcinoma [SCC]: 28 760:792 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 2 8 theme important 301:309 arg1 Saliva 288:293 Saliva 288:293 Saliva 288:293 Saliva is an important source for discovering biomarkers and contains an abundance of biological information. 36349801 2 8 theme important 301:309 arg1 source 311:316 an important source 298:316 an important source for discovering biomarkers 298:343 Saliva is an important source for discovering biomarkers and contains an abundance of biological information. 36349801 1 9 theme leading 189:195 arg1 cancer 170:175 PURPOSE Lung cancer 157:175 PURPOSE Lung cancer (LC) 157:180 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 1 9 theme leading 189:195 arg1 cause 197:201 the leading cause 185:201 the leading cause of cancer-related deaths worldwide 185:236 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 0 10 theme lung 144:147 arg1 cancer 149:154 lung cancer 144:154 lung cancer 144:154 Integrated glycomics strategy for galactosylated-N-glycans recognized by Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer. 36349801 4 11 theme samples 844:850 arg1 glycopatterns 579:591 the glycopatterns 575:591 the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples 575:850 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 8 12 theme 0.700 1525:1529 arg1 AUC 1518:1520 an AUC 1515:1520 an AUC of 0.700 (95% CI: 0.589-0.812) 1515:1551 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 1 13 theme deaths 221:226 arg1 worldwide 228:236 cancer-related deaths worldwide 206:236 cancer-related deaths worldwide 206:236 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 4 14 theme benign 693:698 arg1 [BPD 718:721 benign pulmonary disease [BPD]: 27 693:726 benign pulmonary disease [BPD]: 27 693:726 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 14 theme benign 693:698 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 8 15 theme glycopattern 1413:1424 arg1 levels 1394:1399 the levels 1390:1399 the levels of salivary glycopattern recognized by BS-I 1390:1443 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 4 16 theme disease 710:716 arg1 [BPD 718:721 benign pulmonary disease [BPD]: 27 693:726 benign pulmonary disease [BPD]: 27 693:726 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 16 theme disease 710:716 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 1 17 theme PURPOSE 157:163 arg1 cancer 170:175 PURPOSE Lung cancer 157:175 PURPOSE Lung cancer (LC) 157:180 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 1 17 theme PURPOSE 157:163 arg1 cause 197:201 the leading cause 185:201 the leading cause of cancer-related deaths worldwide 185:236 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 1 17 theme PURPOSE 157:163 arg1 LC 178:179 LC 178:179 LC 178:179 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 10 18 theme biomarkers 2067:2076 arg1 study 2055:2059 the study 2051:2059 the study of LC biomarkers based on precise alterations of galactosylated N-glycans 2051:2133 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 0 19 theme Simplicifolia 84:96 arg1 Lectin 98:103 Bandeiraea Simplicifolia Lectin I 73:105 Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer 73:154 Integrated glycomics strategy for galactosylated-N-glycans recognized by Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer. 36349801 6 20 gly glycoproteins 1020:1032 arg1 glycoproteins 1020:1032 their salivary glycoproteins 1005:1032 their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group 1005:1117 Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS. 36349801 4 21 theme lectin 858:863 arg1 microarrays 865:875 lectin microarrays 858:875 lectin microarrays 858:875 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 8 22 theme lung 1464:1467 arg1 disease 1469:1475 lung disease 1464:1475 lung disease (BPD, ADC, SCC, and SCLC) 1464:1501 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 8 23 with BPD 1578:1580 arg1 AUC 1590:1592 an AUC 1587:1592 an AUC of 0.860 (95% CI: 0.763-0.956) 1587:1623 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 4 24 theme lung 729:732 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 24 theme lung 729:732 arg1 [ADC 749:752 lung adenocarcinoma [ADC]: 39 729:757 lung adenocarcinoma [ADC]: 39 729:757 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 0 25 theme salivary 110:117 arg1 proteins 119:126 salivary proteins 110:126 salivary proteins associated with lung cancer 110:154 Integrated glycomics strategy for galactosylated-N-glycans recognized by Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer. 36349801 2 26 contain contains 349:356 arg1 Saliva 288:293 Saliva 288:293 Saliva 288:293 Saliva is an important source for discovering biomarkers and contains an abundance of biological information. 36349801 2 26 contain contains 349:356 arg2 abundance 361:369 an abundance 358:369 an abundance of biological information 358:395 Saliva is an important source for discovering biomarkers and contains an abundance of biological information. 36349801 2 26 contain contains 349:356 arg1 source 311:316 an important source 298:316 an important source for discovering biomarkers 298:343 Saliva is an important source for discovering biomarkers and contains an abundance of biological information. 36349801 8 27 with disease 1469:1475 arg1 AUC 1518:1520 an AUC 1515:1520 an AUC of 0.700 (95% CI: 0.589-0.812) 1515:1551 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 10 28 theme CLINICAL 1914:1921 arg1 RELEVANCE 1923:1931 CLINICAL RELEVANCE 1914:1931 CLINICAL RELEVANCE 1914:1931 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 2 29 theme information 385:395 arg1 abundance 361:369 an abundance 358:369 an abundance of biological information 358:395 Saliva is an important source for discovering biomarkers and contains an abundance of biological information. 36349801 0 30 theme Integrated 0:9 arg1 strategy 21:28 Integrated glycomics strategy 0:28 Integrated glycomics strategy for galactosylated-N-glycans 0:57 Integrated glycomics strategy for galactosylated-N-glycans recognized by Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer. 36349801 1 31 theme poor 272:275 arg1 prognosis 277:285 poor prognosis 272:285 poor prognosis 272:285 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 10 32 theme galactosylated 2110:2123 arg1 N-glycans 2125:2133 galactosylated N-glycans 2110:2133 galactosylated N-glycans 2110:2133 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 7 33 dep RESULTS 1154:1160 arg1 showed 1174:1179 showed 1174:1179 showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with LC compared with BPD and HV 1174:1323 RESULTS The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with LC compared with BPD and HV. 36349801 4 34 theme cell 769:772 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 34 theme cell 769:772 arg1 [SCC 784:787 squamous cell carcinoma [SCC]: 28 760:792 squamous cell carcinoma [SCC]: 28 760:792 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 9 35 theme galactosylated 1650:1663 arg1 N-glycans 1665:1673 galactosylated N-glycans 1650:1673 galactosylated N-glycans 1650:1673 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 8 36 theme characteristic 1345:1358 arg1 analysis 1366:1373 characteristic (ROC) analysis 1345:1373 characteristic (ROC) analysis 1345:1373 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 3 37 theme galactosylation 449:463 arg1 levels 465:470 galactosylation levels 449:470 galactosylation levels of salivary proteins 449:491 The purpose of this study was to determine whether galactosylation levels of salivary proteins are associated with LC. 36349801 4 38 dep DESIGN 530:535 arg1 analyzed 547:554 analyzed 547:554 analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays 547:875 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 3 39 theme study 418:422 arg1 purpose 402:408 The purpose 398:408 The purpose of this study 398:422 The purpose of this study was to determine whether galactosylation levels of salivary proteins are associated with LC. 36349801 8 40 with LC 1571:1572 arg1 AUC 1590:1592 an AUC 1587:1592 an AUC of 0.860 (95% CI: 0.763-0.956) 1587:1623 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 9 41 theme N-glycan 1794:1801 arg1 m/z 1810:1812 m/z 1828.683, 2418.853 1810:1831 m/z 1810:1812 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 9 41 theme N-glycan 1794:1801 arg1 peaks 1803:1807 two galactosylated N-glycan peaks 1775:1807 two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) 1775:1832 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 5 42 theme blotting 951:958 arg1 technique 960:968 the lectin blotting technique 940:968 the lectin blotting technique 940:968 Pooled samples from each group were subsequently validated by the lectin blotting technique. 36349801 6 43 theme BS-I-magnetic 1050:1062 arg1 conjugates 1073:1082 the BS-I-magnetic particle conjugates 1046:1082 the BS-I-magnetic particle conjugates from pooled samples for each group 1046:1117 Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS. 36349801 3 44 theme proteins 484:491 arg1 levels 465:470 galactosylation levels 449:470 galactosylation levels of salivary proteins 449:491 The purpose of this study was to determine whether galactosylation levels of salivary proteins are associated with LC. 36349801 1 45 theme worldwide 228:236 arg1 cancer 170:175 PURPOSE Lung cancer 157:175 PURPOSE Lung cancer (LC) 157:180 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 1 45 theme worldwide 228:236 arg1 cause 197:201 the leading cause 185:201 the leading cause of cancer-related deaths worldwide 185:236 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 7 46 theme galactosylated 1210:1223 arg1 glycans 1225:1231 galactosylated glycans 1210:1231 galactosylated glycans recognized by BS-I 1210:1250 RESULTS The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with LC compared with BPD and HV. 36349801 4 47 theme Simplicifolia 618:630 arg1 Lectin 632:637 Bandeiraea Simplicifolia Lectin I 607:639 Bandeiraea Simplicifolia Lectin I (BS-I) 607:646 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 47 theme Simplicifolia 618:630 arg1 BS-I 642:645 BS-I 642:645 BS-I 642:645 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 9 48 dep groups 1869:1874 arg1 groups 1869:1874 the LC groups 1862:1874 the LC groups (ADC, SCC, and SCLC) 1862:1895 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 9 48 dep groups 1869:1874 arg1 SCC 1882:1884 SCC 1882:1884 SCC 1882:1884 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 9 48 dep groups 1869:1874 arg1 SCLC 1891:1894 SCLC 1891:1894 SCLC 1891:1894 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 9 48 dep groups 1869:1874 arg1 ADC 1877:1879 ADC 1877:1879 ADC 1877:1879 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 4 49 dep groups 656:661 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 49 dep groups 656:661 arg1 [ADC 749:752 lung adenocarcinoma [ADC]: 39 729:757 lung adenocarcinoma [ADC]: 39 729:757 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 49 dep groups 656:661 arg1 [SCLC 818:822 small-cell lung cancer [SCLC 795:822 small-cell lung cancer [SCLC 795:822 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 49 dep groups 656:661 arg1 [BPD 718:721 benign pulmonary disease [BPD]: 27 693:726 benign pulmonary disease [BPD]: 27 693:726 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 49 dep groups 656:661 arg1 [SCC 784:787 squamous cell carcinoma [SCC]: 28 760:792 squamous cell carcinoma [SCC]: 28 760:792 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 6 50 theme glycoproteins 1020:1032 arg1 profiles 993:1000 the N-glycan profiles 980:1000 the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group 980:1117 Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS. 36349801 8 51 dep disease 1469:1475 arg1 BPD 1478:1480 BPD 1478:1480 BPD 1478:1480 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 8 51 dep disease 1469:1475 arg1 SCC 1488:1490 SCC 1488:1490 SCC 1488:1490 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 8 51 dep disease 1469:1475 arg1 SCLC 1497:1500 SCLC 1497:1500 SCLC 1497:1500 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 8 51 dep disease 1469:1475 arg1 ADC 1483:1485 ADC 1483:1485 ADC 1483:1485 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 4 52 theme small-cell 795:804 arg1 cancer 811:816 small-cell lung cancer 795:816 small-cell lung cancer [SCLC 795:822 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 53 theme glycopatterns 579:591 arg1 alterations 560:570 the alterations 556:570 the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples 556:850 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 9 54 from proportion 1636:1645 arg1 % 1718:1718 39.5% 1714:1718 39.5% 1714:1718 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 9 54 from proportion 1636:1645 arg1 % 1687:1687 38.4% 1683:1687 38.4% 1683:1687 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 9 54 from proportion 1636:1645 arg1 % 1700:1700 43.1% 1696:1700 43.1% 1696:1700 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 9 54 from proportion 1636:1645 arg1 ADC 1678:1680 ADC 1678:1680 ADC (38.4%) 1678:1688 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 9 54 from proportion 1636:1645 arg1 SCC 1691:1693 SCC 1691:1693 SCC (43.1%) 1691:1701 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 9 54 from proportion 1636:1645 arg1 SCLC 1708:1711 SCLC 1708:1711 SCLC (39.5%) 1708:1719 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 4 55 theme cancer 811:816 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 55 theme cancer 811:816 arg1 [SCLC 818:822 small-cell lung cancer [SCLC 795:822 small-cell lung cancer [SCLC 795:822 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 7 56 theme glycans 1225:1231 arg1 level 1201:1205 the expression level 1186:1205 the expression level of galactosylated glycans recognized by BS-I 1186:1250 RESULTS The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with LC compared with BPD and HV. 36349801 9 57 dep increased 1721:1729 arg1 compared 1731:1738 compared 1731:1738 increased compared to HV (30.1%) and BPD (33.7%) 1721:1768 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 10 58 theme crucial 1962:1968 arg1 information 1970:1980 crucial information 1962:1980 crucial information on galactosylated N-linked glycans associated with LC 1962:2034 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 6 59 theme pooled 1089:1094 arg1 samples 1096:1102 pooled samples 1089:1102 pooled samples for each group 1089:1117 Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS. 36349801 4 60 theme healthy 664:670 arg1 volunteers 672:681 healthy volunteers 664:681 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 8 61 theme 0.860 1597:1601 arg1 AUC 1590:1592 an AUC 1587:1592 an AUC of 0.860 (95% CI: 0.763-0.956) 1587:1623 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 1 62 theme cancer-related 206:219 arg1 worldwide 228:236 cancer-related deaths worldwide 206:236 cancer-related deaths worldwide 206:236 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 4 63 theme saliva 837:842 arg1 samples 844:850 144 saliva samples 833:850 144 saliva samples 833:850 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 0 64 from Lectin 98:103 arg1 proteins 119:126 salivary proteins 110:126 salivary proteins associated with lung cancer 110:154 Integrated glycomics strategy for galactosylated-N-glycans recognized by Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer. 36349801 4 65 theme EXPERIMENTAL 517:528 arg1 DESIGN 530:535 EXPERIMENTAL DESIGN 517:535 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 517:876 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 7 66 with patients 1283:1290 arg1 LC 1297:1298 LC 1297:1298 LC 1297:1298 RESULTS The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with LC compared with BPD and HV. 36349801 8 67 with HV 1507:1508 arg1 AUC 1518:1520 an AUC 1515:1520 an AUC of 0.700 (95% CI: 0.589-0.812) 1515:1551 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 10 68 dep CONCLUSIONS 1898:1908 arg1 findings 1939:1946 These findings 1933:1946 These findings 1933:1946 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 4 69 theme pulmonary 700:708 arg1 [BPD 718:721 benign pulmonary disease [BPD]: 27 693:726 benign pulmonary disease [BPD]: 27 693:726 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 69 theme pulmonary 700:708 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 1 70 theme Lung 165:168 arg1 cancer 170:175 PURPOSE Lung cancer 157:175 PURPOSE Lung cancer (LC) 157:180 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 1 70 theme Lung 165:168 arg1 cause 197:201 the leading cause 185:201 the leading cause of cancer-related deaths worldwide 185:236 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 1 70 theme Lung 165:168 arg1 LC 178:179 LC 178:179 LC 178:179 PURPOSE Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. 36349801 10 71 theme LC 2064:2065 arg1 biomarkers 2067:2076 LC biomarkers 2064:2076 LC biomarkers 2064:2076 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 8 72 dep characteristic 1345:1358 arg1 ROC 1361:1363 ROC 1361:1363 ROC 1361:1363 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 5 73 theme Pooled 878:883 arg1 samples 885:891 Pooled samples 878:891 Pooled samples from each group 878:907 Pooled samples from each group were subsequently validated by the lectin blotting technique. 36349801 10 74 theme precise 2087:2093 arg1 alterations 2095:2105 precise alterations 2087:2105 precise alterations of galactosylated N-glycans 2087:2133 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 4 75 theme adenocarcinoma 734:747 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 75 theme adenocarcinoma 734:747 arg1 [ADC 749:752 lung adenocarcinoma [ADC]: 39 729:757 lung adenocarcinoma [ADC]: 39 729:757 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 0 76 theme glycomics 11:19 arg1 strategy 21:28 Integrated glycomics strategy 0:28 Integrated glycomics strategy for galactosylated-N-glycans 0:57 Integrated glycomics strategy for galactosylated-N-glycans recognized by Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer. 36349801 6 77 theme N-glycan 984:991 arg1 profiles 993:1000 the N-glycan profiles 980:1000 the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group 980:1117 Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS. 36349801 10 78 theme N-glycans 2125:2133 arg1 alterations 2095:2105 precise alterations 2087:2105 precise alterations of galactosylated N-glycans 2087:2133 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 2 79 theme biological 374:383 arg1 information 385:395 biological information 374:395 biological information 374:395 Saliva is an important source for discovering biomarkers and contains an abundance of biological information. 36349801 6 80 from samples 1096:1102 arg1 conjugates 1073:1082 the BS-I-magnetic particle conjugates 1046:1082 the BS-I-magnetic particle conjugates from pooled samples for each group 1046:1117 Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS. 36349801 3 81 theme salivary 475:482 arg1 proteins 484:491 salivary proteins 475:491 salivary proteins 475:491 The purpose of this study was to determine whether galactosylation levels of salivary proteins are associated with LC. 36349801 9 82 theme N-glycans 1665:1673 arg1 proportion 1636:1645 the proportion 1632:1645 the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) 1632:1719 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 10 83 from information 1970:1980 arg1 glycans 2009:2015 galactosylated N-linked glycans 1985:2015 galactosylated N-linked glycans associated with LC 1985:2034 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 9 84 theme galactosylated 1779:1792 arg1 m/z 1810:1812 m/z 1828.683, 2418.853 1810:1831 m/z 1810:1812 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 9 84 theme galactosylated 1779:1792 arg1 peaks 1803:1807 two galactosylated N-glycan peaks 1775:1807 two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) 1775:1832 Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). 36349801 4 85 theme squamous 760:767 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 85 theme squamous 760:767 arg1 [SCC 784:787 squamous cell carcinoma [SCC]: 28 760:792 squamous cell carcinoma [SCC]: 28 760:792 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 0 86 theme Bandeiraea 73:82 arg1 Lectin 98:103 Bandeiraea Simplicifolia Lectin I 73:105 Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer 73:154 Integrated glycomics strategy for galactosylated-N-glycans recognized by Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer. 36349801 5 87 theme lectin 944:949 arg1 technique 960:968 the lectin blotting technique 940:968 the lectin blotting technique 940:968 Pooled samples from each group were subsequently validated by the lectin blotting technique. 36349801 6 88 theme particle 1064:1071 arg1 conjugates 1073:1082 the BS-I-magnetic particle conjugates 1046:1082 the BS-I-magnetic particle conjugates from pooled samples for each group 1046:1117 Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS. 36349801 10 89 theme N-linked 2000:2007 arg1 glycans 2009:2015 galactosylated N-linked glycans 1985:2015 galactosylated N-linked glycans associated with LC 1985:2034 CONCLUSIONS AND CLINICAL RELEVANCE These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva. 36349801 4 90 theme carcinoma 774:782 arg1 [HV 683:685 healthy volunteers [HV]: 28 664:690 healthy volunteers [HV]: 28 664:690 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 4 90 theme carcinoma 774:782 arg1 [SCC 784:787 squamous cell carcinoma [SCC]: 28 760:792 squamous cell carcinoma [SCC]: 28 760:792 EXPERIMENTAL DESIGN First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. 36349801 8 91 theme salivary 1404:1411 arg1 glycopattern 1413:1424 salivary glycopattern 1404:1424 salivary glycopattern recognized by BS-I 1404:1443 Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). 36349801 7 92 theme expression 1190:1199 arg1 level 1201:1205 the expression level 1186:1205 the expression level of galactosylated glycans recognized by BS-I 1186:1250 RESULTS The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with LC compared with BPD and HV. 35812534 4 0 theme glomerular 787:796 arg1 GFR 813:815 GFR 813:815 GFR 813:815 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 4 0 theme glomerular 787:796 arg1 rate 807:810 glomerular function rate 787:810 glomerular function rate (GFR) 787:816 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 17 1 theme Serum 2118:2122 arg1 biomarker 2151:2159 a suitable biomarker 2140:2159 a suitable biomarker in CKD patients with declining GFR 2140:2194 Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR. 35812534 17 1 theme Serum 2118:2122 arg1 α-Klotho 2124:2131 Serum α-Klotho 2118:2131 Serum α-Klotho 2118:2131 Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR. 35812534 14 2 with correlation 1855:1865 arg1 eGFR 1872:1875 eGFR 1872:1875 eGFR 1872:1875 Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648). 35812534 0 3 from Marker 56:61 arg1 Patients 159:166 Chronic Kidney Disease (CKD) Patients 130:166 Chronic Kidney Disease (CKD) Patients 130:166 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 10 4 from 2.59±0.98 1542:1550 arg1 cases 1555:1559 cases 1555:1559 cases 1555:1559 Results Serum α-Klotho (ng/ml) was found to be 2.59±0.98 in cases as compared to 0.24±0.09 in controls (p< 0.01). 35812534 3 5 from excretion 565:573 arg1 tubule 585:590 distal tubule 578:590 distal tubule 578:590 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 4 6 theme disease 754:760 arg1 prognosis 762:770 disease prognosis 754:770 disease prognosis 754:770 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 17 7 with patients 2168:2175 arg1 GFR 2192:2194 declining GFR 2182:2194 declining GFR 2182:2194 Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR. 35812534 15 8 theme serum 1933:1937 arg1 level 1948:1952 The serum α-Klotho level 1929:1952 The serum α-Klotho level 1929:1952 Conclusion The serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. 35812534 15 8 theme serum 1933:1937 arg1 higher 1972:1977 higher 1972:1977 higher 1972:1977 Conclusion The serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. 35812534 6 9 theme sex-matched 1034:1044 arg1 volunteers 1054:1063 40 age and sex-matched healthy volunteers 1023:1063 40 age and sex-matched healthy volunteers 1023:1063 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 6 9 theme sex-matched 1034:1044 arg1 control 1079:1085 control 1079:1085 control 1079:1085 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 10 10 from 0.24±0.09 1576:1584 arg1 p< 1599:1600 p< 0.01 1599:1605 p< 0.01 1599:1605 Results Serum α-Klotho (ng/ml) was found to be 2.59±0.98 in cases as compared to 0.24±0.09 in controls (p< 0.01). 35812534 10 10 from 0.24±0.09 1576:1584 arg1 controls 1589:1596 controls 1589:1596 controls (p< 0.01) 1589:1606 Results Serum α-Klotho (ng/ml) was found to be 2.59±0.98 in cases as compared to 0.24±0.09 in controls (p< 0.01). 35812534 6 11 theme age 1026:1028 arg1 volunteers 1054:1063 40 age and sex-matched healthy volunteers 1023:1063 40 age and sex-matched healthy volunteers 1023:1063 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 6 11 theme age 1026:1028 arg1 control 1079:1085 control 1079:1085 control 1079:1085 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 16 12 theme CKD 2104:2106 arg1 patients 2108:2115 CKD patients 2104:2115 CKD patients 2104:2115 Both serum α-Klotho and oxidative stress were negatively correlated with eGFR in CKD patients. 35812534 11 13 theme total 1619:1623 arg1 load 1633:1636 The serum total oxidant load 1609:1636 The serum total oxidant load (ng/ml) 1609:1644 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 11 13 theme total 1619:1623 arg1 ng/ml 1639:1643 ng/ml 1639:1643 ng/ml 1639:1643 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 11 13 theme total 1619:1623 arg1 1.96±1.01 1650:1658 1.96±1.01 1650:1658 1.96±1.01 1650:1658 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 0 14 theme Declining 92:100 arg1 Rate 122:125 Declining Glomerular Function Rate 92:125 Declining Glomerular Function Rate 92:125 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 10 15 theme Results 1495:1501 arg1 ng/ml 1519:1523 ng/ml 1519:1523 ng/ml 1519:1523 Results Serum α-Klotho (ng/ml) was found to be 2.59±0.98 in cases as compared to 0.24±0.09 in controls (p< 0.01). 35812534 10 15 theme Results 1495:1501 arg1 α-Klotho 1509:1516 Results Serum α-Klotho 1495:1516 Results Serum α-Klotho (ng/ml) 1495:1524 Results Serum α-Klotho (ng/ml) was found to be 2.59±0.98 in cases as compared to 0.24±0.09 in controls (p< 0.01). 35812534 0 16 theme Function 113:120 arg1 Rate 122:125 Declining Glomerular Function Rate 92:125 Declining Glomerular Function Rate 92:125 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 4 17 dep highlights 715:724 arg1 seen 702:705 seen 702:705 seen in CKD 702:712 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 8 18 theme reducing 1342:1349 arg1 ability 1351:1357 the ferric reducing ability 1331:1357 the ferric reducing ability of plasma (FRAP) method 1331:1381 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 4 19 theme α-Klotho 639:646 arg1 association 618:628 The association 614:628 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis 614:696 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 4 20 theme oxidative 653:661 arg1 stress 663:668 oxidative stress 653:668 oxidative stress 653:668 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 0 21 theme Kidney 138:143 arg1 CKD 154:156 CKD 154:156 CKD 154:156 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 0 21 theme Kidney 138:143 arg1 Disease 145:151 Chronic Kidney Disease 130:151 Chronic Kidney Disease (CKD) Patients 130:166 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 8 22 theme total 1205:1209 arg1 load 1219:1222 the total oxidant load 1201:1222 the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method 1201:1282 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 3 23 theme calcium 532:538 arg1 absorption 540:549 calcium absorption 532:549 calcium absorption 532:549 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 8 24 theme ferrous 1227:1233 arg1 method 1277:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 0 25 theme Oxidative 66:74 arg1 OS 84:85 OS 84:85 OS 84:85 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 0 25 theme Oxidative 66:74 arg1 Stress 76:81 Oxidative Stress 66:81 Oxidative Stress (OS) 66:86 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 9 26 theme glomerular 1412:1421 arg1 eGFR 1440:1443 eGFR 1440:1443 eGFR 1440:1443 Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation. 35812534 9 26 theme glomerular 1412:1421 arg1 rate 1434:1437 the estimated glomerular filtration rate 1398:1437 the estimated glomerular filtration rate (eGFR) 1398:1444 Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation. 35812534 6 27 theme diagnosed 903:911 arg1 cases 913:917 Fifty diagnosed cases 897:917 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, 897:1002 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 8 28 theme orange 1253:1258 arg1 method 1277:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 7 29 theme Serum 1088:1092 arg1 levels 1103:1108 Serum α-Klotho levels 1088:1108 Serum α-Klotho levels 1088:1108 Serum α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. 35812534 9 30 theme rate 1434:1437 arg1 Estimation 1384:1393 Estimation 1384:1393 Estimation of the estimated glomerular filtration rate (eGFR) 1384:1444 Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation. 35812534 17 31 from biomarker 2151:2159 arg1 patients 2168:2175 CKD patients 2164:2175 CKD patients with declining GFR 2164:2194 Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR. 35812534 5 32 dep Material 819:826 arg1 This 840:843 This 840:843 This 840:843 Material and methods This was a case-control study consisting of 90 subjects. 35812534 3 33 dep found 426:430 arg1 expressed 432:440 expressed 432:440 is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans 423:611 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 14 34 dep = 1908:1908 arg1 r 1894:1894 r 1894:1894 r = -0.065 1894:1903 Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648). 35812534 14 35 theme CKD 1880:1882 arg1 patients 1884:1891 CKD patients 1880:1891 CKD patients (r = -0.065; p = 0.648) 1880:1915 Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648). 35812534 8 36 theme FOX2 1271:1274 arg1 method 1277:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 11 37 from 1.96±1.01 1650:1658 arg1 controls 1687:1694 controls 1687:1694 controls 1687:1694 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 11 37 from 1.96±1.01 1650:1658 arg1 cases 1677:1681 cases 1677:1681 cases 1677:1681 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 0 38 theme Serum 0:4 arg1 Protein 15:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 0 38 theme Serum 0:4 arg1 Marker 56:61 an Independent Predictive Marker 30:61 an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients 30:166 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 12 39 theme total 1717:1721 arg1 281.80±78.0 1765:1775 281.80±78.0 1765:1775 281.80±78.0 1765:1775 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 12 39 theme total 1717:1721 arg1 µM 1745:1746 µM 1745:1746 µM 1745:1746 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 12 39 theme total 1717:1721 arg1 capacity 1735:1742 Serum total antioxidant capacity 1711:1742 Serum total antioxidant capacity (µM) 1711:1747 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 12 39 theme total 1717:1721 arg1 862.82±51.86 1790:1801 862.82±51.86 1790:1801 862.82±51.86 1790:1801 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 7 40 dep enzyme-linked 1130:1142 arg1 immunosorbent 1144:1156 immunosorbent 1144:1156 immunosorbent 1144:1156 Serum α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. 35812534 6 41 theme SCB 966:968 arg1 nephrology 954:963 nephrology 954:963 nephrology 954:963 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 6 41 theme SCB 966:968 arg1 College 978:984 SCB Medical College 966:984 SCB Medical College 966:984 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 17 42 theme suitable 2142:2149 arg1 biomarker 2151:2159 a suitable biomarker 2140:2159 a suitable biomarker in CKD patients with declining GFR 2140:2194 Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR. 35812534 17 42 theme suitable 2142:2149 arg1 α-Klotho 2124:2131 Serum α-Klotho 2118:2131 Serum α-Klotho 2118:2131 Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR. 35812534 2 43 theme species 376:382 arg1 generation 346:355 the generation 342:355 the generation of reactive oxygen species (ROS) 342:388 Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). 35812534 1 44 theme health 243:248 arg1 Introduction 169:180 Introduction Chronic kidney disease (CKD) 169:209 Introduction Chronic kidney disease (CKD) 169:209 Introduction Chronic kidney disease (CKD) has been recognized as a global health problem. 35812534 1 44 theme health 243:248 arg1 problem 250:256 a global health problem 234:256 a global health problem 234:256 Introduction Chronic kidney disease (CKD) has been recognized as a global health problem. 35812534 12 45 from 862.82±51.86 1790:1801 arg1 controls 1806:1813 controls 1806:1813 controls 1806:1813 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 6 46 theme nephrology 954:963 arg1 department 940:949 the department 936:949 the department of nephrology, SCB Medical College, Cuttack, Odisha, 936:1002 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 3 47 theme distal 578:583 arg1 tubule 585:590 distal tubule 578:590 distal tubule 578:590 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 16 48 theme serum 2028:2032 arg1 α-Klotho 2034:2041 serum α-Klotho 2028:2041 serum α-Klotho 2028:2041 Both serum α-Klotho and oxidative stress were negatively correlated with eGFR in CKD patients. 35812534 2 49 theme reactive 360:367 arg1 ROS 385:387 ROS 385:387 ROS 385:387 Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). 35812534 2 49 theme reactive 360:367 arg1 species 376:382 reactive oxygen species 360:382 reactive oxygen species (ROS) 360:388 Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). 35812534 15 50 theme healthy 2003:2009 arg1 volunteers 2011:2020 healthy volunteers 2003:2020 healthy volunteers 2003:2020 Conclusion The serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. 35812534 9 51 theme Cockcroft 1465:1473 arg1 equation 1485:1492 the Cockcroft and Gault equation 1461:1492 the Cockcroft and Gault equation 1461:1492 Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation. 35812534 8 52 theme antioxidant 1298:1308 arg1 capacity 1310:1317 the total antioxidant capacity 1288:1317 the total antioxidant capacity of serum 1288:1326 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 0 53 theme Independent 33:43 arg1 Protein 15:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 0 53 theme Independent 33:43 arg1 Marker 56:61 an Independent Predictive Marker 30:61 an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients 30:166 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 12 54 from 281.80±78.0 1765:1775 arg1 cases 1780:1784 cases 1780:1784 cases 1780:1784 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 9 55 theme Gault 1479:1483 arg1 equation 1485:1492 the Cockcroft and Gault equation 1461:1492 the Cockcroft and Gault equation 1461:1492 Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation. 35812534 17 56 theme declining 2182:2190 arg1 GFR 2192:2194 declining GFR 2182:2194 declining GFR 2182:2194 Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR. 35812534 2 57 theme advanced 281:288 arg1 stages 290:295 advanced stages 281:295 advanced stages 281:295 Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). 35812534 3 58 link N-linked 596:603 arg1 glycans 605:611 N-linked glycans 596:611 N-linked glycans 596:611 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 2 59 theme significant 318:328 arg1 increase 330:337 a significant increase 316:337 a significant increase in the generation of reactive oxygen species (ROS) 316:388 Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). 35812534 7 60 theme assay 1158:1162 arg1 kits 1164:1167 enzyme-linked immunosorbent assay kits 1130:1167 enzyme-linked immunosorbent assay kits 1130:1167 Serum α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. 35812534 7 61 theme α-Klotho 1094:1101 arg1 levels 1103:1108 Serum α-Klotho levels 1088:1108 Serum α-Klotho levels 1088:1108 Serum α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. 35812534 7 62 theme enzyme-linked 1130:1142 arg1 kits 1164:1167 enzyme-linked immunosorbent assay kits 1130:1167 enzyme-linked immunosorbent assay kits 1130:1167 Serum α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. 35812534 4 63 theme function 798:805 arg1 GFR 813:815 GFR 813:815 GFR 813:815 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 4 63 theme function 798:805 arg1 rate 807:810 glomerular function rate 787:810 glomerular function rate (GFR) 787:816 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 15 64 theme α-Klotho 1939:1946 arg1 level 1948:1952 The serum α-Klotho level 1929:1952 The serum α-Klotho level 1929:1952 Conclusion The serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. 35812534 15 64 theme α-Klotho 1939:1946 arg1 higher 1972:1977 higher 1972:1977 higher 1972:1977 Conclusion The serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. 35812534 4 65 with association 618:628 arg1 inflammation 671:682 inflammation 671:682 inflammation 671:682 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 4 65 with association 618:628 arg1 fibrosis 689:696 fibrosis 689:696 fibrosis 689:696 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 4 65 with association 618:628 arg1 stress 663:668 oxidative stress 653:668 oxidative stress 653:668 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 3 66 theme convoluted 456:465 arg1 tubules 467:473 the distal convoluted tubules 445:473 the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans 445:611 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 6 67 theme healthy 1046:1052 arg1 volunteers 1054:1063 40 age and sex-matched healthy volunteers 1023:1063 40 age and sex-matched healthy volunteers 1023:1063 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 6 67 theme healthy 1046:1052 arg1 control 1079:1085 control 1079:1085 control 1079:1085 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 2 68 theme CKD 274:276 arg1 Progression 259:269 Progression 259:269 Progression of CKD to advanced stages 259:295 Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). 35812534 0 69 theme Glomerular 102:111 arg1 Rate 122:125 Declining Glomerular Function Rate 92:125 Declining Glomerular Function Rate 92:125 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 3 70 theme kidney 482:487 arg1 tubules 467:473 the distal convoluted tubules 445:473 the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans 445:611 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 7 71 link enzyme-linked 1130:1142 arg1 kits 1164:1167 enzyme-linked immunosorbent assay kits 1130:1167 enzyme-linked immunosorbent assay kits 1130:1167 Serum α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. 35812534 8 72 theme ferric 1335:1340 arg1 ability 1351:1357 the ferric reducing ability 1331:1357 the ferric reducing ability of plasma (FRAP) method 1331:1381 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 6 73 theme 40 1023:1024 arg1 age 1026:1028 age 1026:1028 age 1026:1028 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 10 74 theme Serum 1503:1507 arg1 ng/ml 1519:1523 ng/ml 1519:1523 ng/ml 1519:1523 Results Serum α-Klotho (ng/ml) was found to be 2.59±0.98 in cases as compared to 0.24±0.09 in controls (p< 0.01). 35812534 10 74 theme Serum 1503:1507 arg1 α-Klotho 1509:1516 Results Serum α-Klotho 1495:1516 Results Serum α-Klotho (ng/ml) 1495:1524 Results Serum α-Klotho (ng/ml) was found to be 2.59±0.98 in cases as compared to 0.24±0.09 in controls (p< 0.01). 35812534 11 75 theme oxidant 1625:1631 arg1 load 1633:1636 The serum total oxidant load 1609:1636 The serum total oxidant load (ng/ml) 1609:1644 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 11 75 theme oxidant 1625:1631 arg1 ng/ml 1639:1643 ng/ml 1639:1643 ng/ml 1639:1643 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 11 75 theme oxidant 1625:1631 arg1 1.96±1.01 1650:1658 1.96±1.01 1650:1658 1.96±1.01 1650:1658 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 0 76 theme Rate 122:125 arg1 Protein 15:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 0 76 theme Rate 122:125 arg1 Marker 56:61 an Independent Predictive Marker 30:61 an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients 30:166 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 1 77 theme Chronic 182:188 arg1 CKD 206:208 CKD 206:208 CKD 206:208 Introduction Chronic kidney disease (CKD) has been recognized as a global health problem. 35812534 1 77 theme Chronic 182:188 arg1 disease 197:203 Chronic kidney disease 182:203 Introduction Chronic kidney disease (CKD) 169:209 Introduction Chronic kidney disease (CKD) has been recognized as a global health problem. 35812534 14 78 dep patients 1884:1891 arg1 = 1908:1908 = 1908:1908 = 1908:1908 Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648). 35812534 15 79 dep Conclusion 1918:1927 arg1 level 1948:1952 The serum α-Klotho level 1929:1952 The serum α-Klotho level 1929:1952 Conclusion The serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. 35812534 15 79 dep Conclusion 1918:1927 arg1 higher 1972:1977 higher 1972:1977 higher 1972:1977 Conclusion The serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. 35812534 8 80 theme Oxidative 1170:1178 arg1 stress 1180:1185 Oxidative stress 1170:1185 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 1170:1382 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 0 81 theme Chronic 130:136 arg1 CKD 154:156 CKD 154:156 CKD 154:156 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 0 81 theme Chronic 130:136 arg1 Disease 145:151 Chronic Kidney Disease 130:151 Chronic Kidney Disease (CKD) Patients 130:166 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 15 82 theme CKD 1982:1984 arg1 patients 1986:1993 CKD patients 1982:1993 CKD patients 1982:1993 Conclusion The serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. 35812534 8 83 theme plasma 1362:1367 arg1 method 1376:1381 plasma (FRAP) method 1362:1381 plasma (FRAP) method 1362:1381 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 4 84 theme serum 633:637 arg1 α-Klotho 639:646 serum α-Klotho 633:646 serum α-Klotho 633:646 The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR). 35812534 16 85 theme oxidative 2047:2055 arg1 stress 2057:2062 oxidative stress 2047:2062 oxidative stress 2047:2062 Both serum α-Klotho and oxidative stress were negatively correlated with eGFR in CKD patients. 35812534 0 86 theme Disease 145:151 arg1 Patients 159:166 Chronic Kidney Disease (CKD) Patients 130:166 Chronic Kidney Disease (CKD) Patients 130:166 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 8 87 theme FRAP 1370:1373 arg1 method 1376:1381 plasma (FRAP) method 1362:1381 plasma (FRAP) method 1362:1381 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 6 88 theme CKD 922:924 arg1 cases 913:917 Fifty diagnosed cases 897:917 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, 897:1002 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 8 89 theme method 1376:1381 arg1 ability 1351:1357 the ferric reducing ability 1331:1357 the ferric reducing ability of plasma (FRAP) method 1331:1381 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 14 90 contain has 1840:1842 arg2 correlation 1855:1865 a negative correlation 1844:1865 a negative correlation with eGFR 1844:1875 Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648). 35812534 14 90 contain has 1840:1842 arg1 Klotho 1833:1838 Serum Klotho 1827:1838 Serum Klotho 1827:1838 Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648). 35812534 8 91 theme oxidant 1211:1217 arg1 load 1219:1222 the total oxidant load 1201:1222 the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method 1201:1282 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 0 92 theme Stress 76:81 arg1 Protein 15:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 0 92 theme Stress 76:81 arg1 Marker 56:61 an Independent Predictive Marker 30:61 an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients 30:166 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 9 93 theme estimated 1402:1410 arg1 eGFR 1440:1443 eGFR 1440:1443 eGFR 1440:1443 Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation. 35812534 9 93 theme estimated 1402:1410 arg1 rate 1434:1437 the estimated glomerular filtration rate 1398:1437 the estimated glomerular filtration rate (eGFR) 1398:1444 Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation. 35812534 11 94 theme serum 1613:1617 arg1 load 1633:1636 The serum total oxidant load 1609:1636 The serum total oxidant load (ng/ml) 1609:1644 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 11 94 theme serum 1613:1617 arg1 ng/ml 1639:1643 ng/ml 1639:1643 ng/ml 1639:1643 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 11 94 theme serum 1613:1617 arg1 1.96±1.01 1650:1658 1.96±1.01 1650:1658 1.96±1.01 1650:1658 The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. 35812534 9 95 theme filtration 1423:1432 arg1 eGFR 1440:1443 eGFR 1440:1443 eGFR 1440:1443 Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation. 35812534 9 95 theme filtration 1423:1432 arg1 rate 1434:1437 the estimated glomerular filtration rate 1398:1437 the estimated glomerular filtration rate (eGFR) 1398:1444 Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation. 35812534 8 96 theme oxidation-xylenol 1235:1251 arg1 method 1277:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 12 97 theme Serum 1711:1715 arg1 281.80±78.0 1765:1775 281.80±78.0 1765:1775 281.80±78.0 1765:1775 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 12 97 theme Serum 1711:1715 arg1 µM 1745:1746 µM 1745:1746 µM 1745:1746 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 12 97 theme Serum 1711:1715 arg1 capacity 1735:1742 Serum total antioxidant capacity 1711:1742 Serum total antioxidant capacity (µM) 1711:1747 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 12 97 theme Serum 1711:1715 arg1 862.82±51.86 1790:1801 862.82±51.86 1790:1801 862.82±51.86 1790:1801 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 8 98 theme version 1260:1266 arg1 method 1277:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 3 99 from absorption 540:549 arg1 tubule 585:590 distal tubule 578:590 distal tubule 578:590 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 0 100 theme α-Klotho 6:13 arg1 Protein 15:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 0 100 theme α-Klotho 6:13 arg1 Marker 56:61 an Independent Predictive Marker 30:61 an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients 30:166 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 12 101 theme antioxidant 1723:1733 arg1 281.80±78.0 1765:1775 281.80±78.0 1765:1775 281.80±78.0 1765:1775 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 12 101 theme antioxidant 1723:1733 arg1 µM 1745:1746 µM 1745:1746 µM 1745:1746 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 12 101 theme antioxidant 1723:1733 arg1 capacity 1735:1742 Serum total antioxidant capacity 1711:1742 Serum total antioxidant capacity (µM) 1711:1747 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 12 101 theme antioxidant 1723:1733 arg1 862.82±51.86 1790:1801 862.82±51.86 1790:1801 862.82±51.86 1790:1801 Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. 35812534 16 102 from eGFR 2096:2099 arg1 patients 2108:2115 CKD patients 2104:2115 CKD patients 2104:2115 Both serum α-Klotho and oxidative stress were negatively correlated with eGFR in CKD patients. 35812534 6 103 theme Medical 970:976 arg1 nephrology 954:963 nephrology 954:963 nephrology 954:963 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 6 103 theme Medical 970:976 arg1 College 978:984 SCB Medical College 966:984 SCB Medical College 966:984 Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. 35812534 1 104 theme global 236:241 arg1 Introduction 169:180 Introduction Chronic kidney disease (CKD) 169:209 Introduction Chronic kidney disease (CKD) 169:209 Introduction Chronic kidney disease (CKD) has been recognized as a global health problem. 35812534 1 104 theme global 236:241 arg1 problem 250:256 a global health problem 234:256 a global health problem 234:256 Introduction Chronic kidney disease (CKD) has been recognized as a global health problem. 35812534 5 105 theme case-control 851:862 arg1 study 864:868 a case-control study 849:868 a case-control study consisting of 90 subjects 849:894 Material and methods This was a case-control study consisting of 90 subjects. 35812534 5 105 theme case-control 851:862 arg1 methods 832:838 methods 832:838 methods 832:838 Material and methods This was a case-control study consisting of 90 subjects. 35812534 5 105 theme case-control 851:862 arg1 Material 819:826 Material 819:826 Material 819:826 Material and methods This was a case-control study consisting of 90 subjects. 35812534 8 106 theme 2  1268:1269 arg1 method 1277:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 ferrous oxidation-xylenol orange version 2 (FOX2) method 1227:1282 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 2 107 theme oxygen 369:374 arg1 ROS 385:387 ROS 385:387 ROS 385:387 Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). 35812534 2 107 theme oxygen 369:374 arg1 species 376:382 reactive oxygen species 360:382 reactive oxygen species (ROS) 360:388 Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). 35812534 17 108 theme CKD 2164:2166 arg1 patients 2168:2175 CKD patients 2164:2175 CKD patients with declining GFR 2164:2194 Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR. 35812534 14 109 theme negative 1846:1853 arg1 correlation 1855:1865 a negative correlation 1844:1865 a negative correlation with eGFR 1844:1875 Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648). 35812534 3 110 theme potassium 555:563 arg1 excretion 565:573 potassium excretion 555:573 potassium excretion 555:573 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 3 111 theme antiaging 394:402 arg1 α-Klotho 413:420 α-Klotho 413:420 α-Klotho 413:420 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 3 111 theme antiaging 394:402 arg1 protein 404:410 An antiaging protein 391:410 An antiaging protein 391:410 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 0 112 theme Predictive 45:54 arg1 Protein 15:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein 0:21 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 0 112 theme Predictive 45:54 arg1 Marker 56:61 an Independent Predictive Marker 30:61 an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients 30:166 Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients. 35812534 2 113 from increase 330:337 arg1 generation 346:355 the generation 342:355 the generation of reactive oxygen species (ROS) 342:388 Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). 35812534 3 114 theme N-linked 596:603 arg1 glycans 605:611 N-linked glycans 596:611 N-linked glycans 596:611 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35812534 8 115 theme total 1292:1296 arg1 capacity 1310:1317 the total antioxidant capacity 1288:1317 the total antioxidant capacity of serum 1288:1326 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 1 116 dep Introduction 169:180 arg1 CKD 206:208 CKD 206:208 CKD 206:208 Introduction Chronic kidney disease (CKD) has been recognized as a global health problem. 35812534 1 116 dep Introduction 169:180 arg1 disease 197:203 Chronic kidney disease 182:203 Introduction Chronic kidney disease (CKD) 169:209 Introduction Chronic kidney disease (CKD) has been recognized as a global health problem. 35812534 14 117 theme Serum 1827:1831 arg1 Klotho 1833:1838 Serum Klotho 1827:1838 Serum Klotho 1827:1838 Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648). 35812534 1 118 theme kidney 190:195 arg1 CKD 206:208 CKD 206:208 CKD 206:208 Introduction Chronic kidney disease (CKD) has been recognized as a global health problem. 35812534 1 118 theme kidney 190:195 arg1 disease 197:203 Chronic kidney disease 182:203 Introduction Chronic kidney disease (CKD) 169:209 Introduction Chronic kidney disease (CKD) has been recognized as a global health problem. 35812534 8 119 theme serum 1322:1326 arg1 load 1219:1222 the total oxidant load 1201:1222 the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method 1201:1282 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 8 119 theme serum 1322:1326 arg1 capacity 1310:1317 the total antioxidant capacity 1288:1317 the total antioxidant capacity of serum 1288:1326 Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. 35812534 3 120 theme distal 449:454 arg1 tubules 467:473 the distal convoluted tubules 445:473 the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans 445:611 An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. 35487958 7 0 theme specific 1536:1543 arg1 antibodies 1549:1558 SARS-CoV-2 specific IgG antibodies 1525:1558 SARS-CoV-2 specific IgG antibodies 1525:1558 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 8 1 theme biocontainment 1732:1745 arg1 requirements 1747:1758 minimal biocontainment requirements 1724:1758 minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics 1724:1856 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 3 2 theme histidine 763:771 arg1 strain 785:790 a histidine auxotrophic strain 761:790 a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids 761:870 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 4 3 theme whole 899:903 arg1 algae-RBD 920:928 algae-RBD 920:928 algae-RBD 920:928 The RBD was purified from whole cell extracts (algae-RBD) with yield compromised by the finding that 90-95% of expressed RBD lacked the genetically encoded C-terminal 6X-histidine tag. 35487958 4 3 theme whole 899:903 arg1 extracts 910:917 whole cell extracts 899:917 whole cell extracts (algae-RBD) 899:929 The RBD was purified from whole cell extracts (algae-RBD) with yield compromised by the finding that 90-95% of expressed RBD lacked the genetically encoded C-terminal 6X-histidine tag. 35487958 7 4 used used 1479:1482 arg2 algae-RBD 1462:1470 the algae-RBD 1458:1470 the algae-RBD 1458:1470 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 3 5 theme growth 590:595 arg1 media 597:601 growth media 590:601 growth media 590:601 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 8 6 theme inducible 1768:1776 arg1 production 1778:1787 the inducible production 1764:1787 the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics 1764:1856 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 7 7 theme flow 1497:1500 arg1 device 1508:1513 a lateral flow assay device 1487:1513 a lateral flow assay device 1487:1513 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 6 8 theme anti-RBD 1304:1311 arg1 antibodies 1324:1333 anti-RBD polyclonal antibodies 1304:1333 anti-RBD polyclonal antibodies 1304:1333 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 3 9 theme receptor-binding 629:644 arg1 RBD 654:656 RBD 654:656 RBD 654:656 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 3 9 theme receptor-binding 629:644 arg1 domain 646:651 the receptor-binding domain 625:651 the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter 625:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 3 9 theme receptor-binding 629:644 arg1 protein 683:689 the SARS-CoV-2 spike protein 662:689 the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter 662:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 6 10 gly glycosylated 1231:1242 arg1 algae-RBD 1196:1204 Purified algae-RBD 1187:1204 Purified algae-RBD 1187:1204 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 3 11 theme antibiotic 828:837 arg1 selection 839:847 antibiotic selection 828:847 antibiotic selection of expression plasmids 828:870 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 6 12 theme mammalian 1391:1399 arg1 lines 1406:1410 mammalian cell lines 1391:1410 mammalian cell lines 1391:1410 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 5 13 theme C-terminal 1123:1132 arg1 tag 1147:1149 C-terminal 6X-histidine tag 1123:1149 C-terminal 6X-histidine tag 1123:1149 Constructs that lacked the TEV protease site between the RBD and C-terminal 6X-histidine tag retained the tag, increasing yield. 35487958 8 14 theme coronavirus 1812:1822 arg1 antigens 1824:1831 other coronavirus antigens 1806:1831 other coronavirus antigens for pandemic diagnostics 1806:1856 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 1 15 theme synthetic 243:251 arg1 approach 261:268 a synthetic biology approach 241:268 a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research 241:393 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 5 16 theme protease 1089:1096 arg1 site 1098:1101 the TEV protease site 1081:1101 the TEV protease site between the RBD and C-terminal 6X-histidine tag 1081:1149 Constructs that lacked the TEV protease site between the RBD and C-terminal 6X-histidine tag retained the tag, increasing yield. 35487958 1 17 theme worldwide 143:151 arg1 pandemic 162:169 The worldwide COVID-19 pandemic 139:169 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus 139:210 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 3 18 theme plasmids 863:870 arg1 selection 839:847 antibiotic selection 828:847 antibiotic selection of expression plasmids 828:870 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 6 19 theme recombinant 1361:1371 arg1 RBD 1373:1375 recombinant RBD 1361:1375 recombinant RBD purified from mammalian cell lines 1361:1410 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 3 20 theme spike 677:681 arg1 protein 683:689 the SARS-CoV-2 spike protein 662:689 the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter 662:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 7 21 theme mammalian 1640:1648 arg1 lines 1655:1659 mammalian cell lines 1640:1659 mammalian cell lines 1640:1659 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 6 22 with cross-reactive 1284:1297 arg1 antibodies 1324:1333 anti-RBD polyclonal antibodies 1304:1333 anti-RBD polyclonal antibodies 1304:1333 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 2 23 theme SARS-CoV-2 538:547 arg1 proteins 549:556 SARS-CoV-2 proteins 538:556 SARS-CoV-2 proteins 538:556 Here, we adapt plasmid-based systems in the eukaryotic microalgae Phaeodactylum tricornutum to develop an inducible overexpression system for SARS-CoV-2 proteins. 35487958 0 24 theme Phaeodactylum 87:99 arg1 tricornutum 101:111 the diatom Phaeodactylum tricornutum 76:111 the diatom Phaeodactylum tricornutum for pandemic diagnostics 76:136 Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics. 35487958 1 25 theme basic 369:373 arg1 research 386:393 basic biomedical research 369:393 basic biomedical research 369:393 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 1 26 theme SARS-CoV-2 185:194 arg1 betacoronavirus 196:210 the SARS-CoV-2 betacoronavirus 181:210 the SARS-CoV-2 betacoronavirus 181:210 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 4 27 theme expressed 984:992 arg1 RBD 994:996 expressed RBD 984:996 expressed RBD 984:996 The RBD was purified from whole cell extracts (algae-RBD) with yield compromised by the finding that 90-95% of expressed RBD lacked the genetically encoded C-terminal 6X-histidine tag. 35487958 6 28 theme ACE2 1425:1428 arg1 receptor 1430:1437 the human ACE2 receptor 1415:1437 the human ACE2 receptor 1415:1437 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 0 29 theme Phosphate-regulated 0:18 arg1 expression 20:29 Phosphate-regulated expression 0:29 Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics. 0:137 Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics. 35487958 1 30 theme antigen 319:325 arg1 sources 302:308 reliable and scalable sources 280:308 reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research 280:393 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 3 31 theme P. 700:701 arg1 promoter 721:728 the P. tricornutum HASP1 promoter 696:728 the P. tricornutum HASP1 promoter 696:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 0 32 theme SARS-CoV-2 38:47 arg1 domain 66:71 the SARS-CoV-2 receptor-binding domain 34:71 the SARS-CoV-2 receptor-binding domain 34:71 Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics. 35487958 2 33 theme overexpression 512:525 arg1 system 527:532 an inducible overexpression system 499:532 an inducible overexpression system for SARS-CoV-2 proteins 499:556 Here, we adapt plasmid-based systems in the eukaryotic microalgae Phaeodactylum tricornutum to develop an inducible overexpression system for SARS-CoV-2 proteins. 35487958 2 34 theme inducible 502:510 arg1 system 527:532 an inducible overexpression system 499:532 an inducible overexpression system for SARS-CoV-2 proteins 499:556 Here, we adapt plasmid-based systems in the eukaryotic microalgae Phaeodactylum tricornutum to develop an inducible overexpression system for SARS-CoV-2 proteins. 35487958 0 35 theme domain 66:71 arg1 expression 20:29 Phosphate-regulated expression 0:29 Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics. 0:137 Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics. 35487958 5 36 theme TEV 1085:1087 arg1 site 1098:1101 the TEV protease site 1081:1101 the TEV protease site between the RBD and C-terminal 6X-histidine tag 1081:1149 Constructs that lacked the TEV protease site between the RBD and C-terminal 6X-histidine tag retained the tag, increasing yield. 35487958 2 37 from systems 425:431 arg1 microalgae 451:460 the eukaryotic microalgae 436:460 the eukaryotic microalgae 436:460 Here, we adapt plasmid-based systems in the eukaryotic microalgae Phaeodactylum tricornutum to develop an inducible overexpression system for SARS-CoV-2 proteins. 35487958 1 38 theme biology 253:259 arg1 approach 261:268 a synthetic biology approach 241:268 a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research 241:393 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 7 39 theme IgG 1545:1547 arg1 antibodies 1549:1558 SARS-CoV-2 specific IgG antibodies 1525:1558 SARS-CoV-2 specific IgG antibodies 1525:1558 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 3 40 theme HASP1 715:719 arg1 promoter 721:728 the P. tricornutum HASP1 promoter 696:728 the P. tricornutum HASP1 promoter 696:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 7 41 theme SARS-CoV-2 1525:1534 arg1 antibodies 1549:1558 SARS-CoV-2 specific IgG antibodies 1525:1558 SARS-CoV-2 specific IgG antibodies 1525:1558 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 3 42 from promoter 721:728 arg1 RBD 654:656 RBD 654:656 RBD 654:656 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 3 42 from promoter 721:728 arg1 domain 646:651 the receptor-binding domain 625:651 the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter 625:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 3 42 from promoter 721:728 arg1 protein 683:689 the SARS-CoV-2 spike protein 662:689 the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter 662:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 4 43 theme C-terminal 1029:1038 arg1 tag 1053:1055 the genetically encoded C-terminal 6X-histidine tag 1005:1055 the genetically encoded C-terminal 6X-histidine tag 1005:1055 The RBD was purified from whole cell extracts (algae-RBD) with yield compromised by the finding that 90-95% of expressed RBD lacked the genetically encoded C-terminal 6X-histidine tag. 35487958 1 44 theme reliable 280:287 arg1 sources 302:308 reliable and scalable sources 280:308 reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research 280:393 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 3 45 theme wild-type 737:745 arg1 strain 747:752 the wild-type strain 733:752 the wild-type strain 733:752 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 8 46 theme minimal 1724:1730 arg1 requirements 1747:1758 minimal biocontainment requirements 1724:1758 minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics 1724:1856 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 1 47 theme scalable 293:300 arg1 sources 302:308 reliable and scalable sources 280:308 reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research 280:393 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 7 48 theme assay 1502:1506 arg1 device 1508:1513 a lateral flow assay device 1487:1513 a lateral flow assay device 1487:1513 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 3 49 theme auxotrophic 773:783 arg1 strain 785:790 a histidine auxotrophic strain 761:790 a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids 761:870 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 7 50 theme lateral 1489:1495 arg1 device 1508:1513 a lateral flow assay device 1487:1513 a lateral flow assay device 1487:1513 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 6 51 theme polyclonal 1313:1322 arg1 antibodies 1324:1333 anti-RBD polyclonal antibodies 1304:1333 anti-RBD polyclonal antibodies 1304:1333 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 4 52 theme cell 905:908 arg1 algae-RBD 920:928 algae-RBD 920:928 algae-RBD 920:928 The RBD was purified from whole cell extracts (algae-RBD) with yield compromised by the finding that 90-95% of expressed RBD lacked the genetically encoded C-terminal 6X-histidine tag. 35487958 4 52 theme cell 905:908 arg1 extracts 910:917 whole cell extracts 899:917 whole cell extracts (algae-RBD) 899:929 The RBD was purified from whole cell extracts (algae-RBD) with yield compromised by the finding that 90-95% of expressed RBD lacked the genetically encoded C-terminal 6X-histidine tag. 35487958 6 53 theme Purified 1187:1194 arg1 algae-RBD 1196:1204 Purified algae-RBD 1187:1204 Purified algae-RBD 1187:1204 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 6 54 theme cell 1401:1404 arg1 lines 1406:1410 mammalian cell lines 1391:1410 mammalian cell lines 1391:1410 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 8 55 theme SARS-CoV-2 1792:1801 arg1 production 1778:1787 the inducible production 1764:1787 the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics 1764:1856 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 6 56 dep N-linked 1222:1229 arg1 glycosylated 1231:1242 glycosylated 1231:1242 glycosylated by treatment with endoglycosidases 1231:1277 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 5 57 theme 6X-histidine 1134:1145 arg1 tag 1147:1149 C-terminal 6X-histidine tag 1123:1149 C-terminal 6X-histidine tag 1123:1149 Constructs that lacked the TEV protease site between the RBD and C-terminal 6X-histidine tag retained the tag, increasing yield. 35487958 3 58 theme domain 646:651 arg1 expression 611:620 expression 611:620 expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids 611:870 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 8 59 theme other 1806:1810 arg1 antigens 1824:1831 other coronavirus antigens 1806:1831 other coronavirus antigens for pandemic diagnostics 1806:1856 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 7 60 theme cell 1650:1653 arg1 lines 1655:1659 mammalian cell lines 1640:1659 mammalian cell lines 1640:1659 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 3 61 from expression 611:620 arg1 strain 747:752 the wild-type strain 733:752 the wild-type strain 733:752 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 3 61 from expression 611:620 arg1 strain 785:790 a histidine auxotrophic strain 761:790 a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids 761:870 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 6 62 theme RBD 1373:1375 arg1 binding 1350:1356 binding 1350:1356 binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor 1350:1437 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 3 63 theme SARS-CoV-2 666:675 arg1 protein 683:689 the SARS-CoV-2 spike protein 662:689 the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter 662:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 8 64 theme antigens 1824:1831 arg1 production 1778:1787 the inducible production 1764:1787 the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics 1764:1856 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 1 65 theme COVID-19 153:160 arg1 pandemic 162:169 The worldwide COVID-19 pandemic 139:169 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus 139:210 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 0 66 theme diatom 80:85 arg1 tricornutum 101:111 the diatom Phaeodactylum tricornutum 76:111 the diatom Phaeodactylum tricornutum for pandemic diagnostics 76:136 Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics. 35487958 8 67 theme pandemic 1837:1844 arg1 diagnostics 1846:1856 pandemic diagnostics 1837:1856 pandemic diagnostics 1837:1856 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 3 68 theme expression 852:861 arg1 plasmids 863:870 expression plasmids 852:870 expression plasmids 852:870 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 6 69 with treatment 1247:1255 arg1 endoglycosidases 1262:1277 endoglycosidases 1262:1277 endoglycosidases 1262:1277 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 4 70 theme encoded 1021:1027 arg1 tag 1053:1055 the genetically encoded C-terminal 6X-histidine tag 1005:1055 the genetically encoded C-terminal 6X-histidine tag 1005:1055 The RBD was purified from whole cell extracts (algae-RBD) with yield compromised by the finding that 90-95% of expressed RBD lacked the genetically encoded C-terminal 6X-histidine tag. 35487958 0 71 from expression 20:29 arg1 tricornutum 101:111 the diatom Phaeodactylum tricornutum 76:111 the diatom Phaeodactylum tricornutum for pandemic diagnostics 76:136 Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics. 35487958 0 72 theme pandemic 117:124 arg1 diagnostics 126:136 pandemic diagnostics 117:136 pandemic diagnostics 117:136 Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics. 35487958 1 73 theme biomedical 375:384 arg1 research 386:393 basic biomedical research 369:393 basic biomedical research 369:393 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 6 74 theme human 1419:1423 arg1 receptor 1430:1437 the human ACE2 receptor 1415:1437 the human ACE2 receptor 1415:1437 Purified algae-RBD was found to be N-linked glycosylated by treatment with endoglycosidases, was cross-reactive with anti-RBD polyclonal antibodies, and inhibited binding of recombinant RBD purified from mammalian cell lines to the human ACE2 receptor. 35487958 4 75 theme RBD 994:996 arg1 RBD 994:996 expressed RBD 984:996 expressed RBD 984:996 The RBD was purified from whole cell extracts (algae-RBD) with yield compromised by the finding that 90-95% of expressed RBD lacked the genetically encoded C-terminal 6X-histidine tag. 35487958 4 75 theme RBD 994:996 arg1 % 979:979 90-95% 974:979 90-95% of expressed RBD 974:996 The RBD was purified from whole cell extracts (algae-RBD) with yield compromised by the finding that 90-95% of expressed RBD lacked the genetically encoded C-terminal 6X-histidine tag. 35487958 2 76 theme plasmid-based 411:423 arg1 systems 425:431 plasmid-based systems 411:431 plasmid-based systems in the eukaryotic microalgae 411:460 Here, we adapt plasmid-based systems in the eukaryotic microalgae Phaeodactylum tricornutum to develop an inducible overexpression system for SARS-CoV-2 proteins. 35487958 3 77 from domain 646:651 arg1 promoter 721:728 the P. tricornutum HASP1 promoter 696:728 the P. tricornutum HASP1 promoter 696:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 1 78 theme viral 313:317 arg1 antigen 319:325 viral antigen 313:325 viral antigen 313:325 The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. 35487958 2 79 theme eukaryotic 440:449 arg1 microalgae 451:460 the eukaryotic microalgae 436:460 the eukaryotic microalgae 436:460 Here, we adapt plasmid-based systems in the eukaryotic microalgae Phaeodactylum tricornutum to develop an inducible overexpression system for SARS-CoV-2 proteins. 35487958 0 80 theme receptor-binding 49:64 arg1 domain 66:71 the SARS-CoV-2 receptor-binding domain 34:71 the SARS-CoV-2 receptor-binding domain 34:71 Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics. 35487958 7 81 theme equivalent 1592:1601 arg1 sensitivity 1580:1590 sensitivity 1580:1590 sensitivity equivalent to assays performed with RBD made in mammalian cell lines 1580:1659 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 4 82 theme 6X-histidine 1040:1051 arg1 tag 1053:1055 the genetically encoded C-terminal 6X-histidine tag 1005:1055 the genetically encoded C-terminal 6X-histidine tag 1005:1055 The RBD was purified from whole cell extracts (algae-RBD) with yield compromised by the finding that 90-95% of expressed RBD lacked the genetically encoded C-terminal 6X-histidine tag. 35487958 3 83 theme protein 683:689 arg1 RBD 654:656 RBD 654:656 RBD 654:656 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 3 83 theme protein 683:689 arg1 domain 646:651 the receptor-binding domain 625:651 the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter 625:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 3 83 theme protein 683:689 arg1 protein 683:689 the SARS-CoV-2 spike protein 662:689 the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter 662:728 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35487958 7 84 theme donor 1565:1569 arg1 serum 1571:1575 donor serum 1565:1575 donor serum 1565:1575 We also show that the algae-RBD can be used in a lateral flow assay device to detect SARS-CoV-2 specific IgG antibodies from donor serum at sensitivity equivalent to assays performed with RBD made in mammalian cell lines. 35487958 8 85 with system 1712:1717 arg1 requirements 1747:1758 minimal biocontainment requirements 1724:1758 minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics 1724:1856 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 8 86 theme scalable 1703:1710 arg1 tricornutum 1686:1696 P. tricornutum 1683:1696 P. tricornutum 1683:1696 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 8 86 theme scalable 1703:1710 arg1 system 1712:1717 a scalable system 1701:1717 a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics 1701:1856 Our study shows that P. tricornutum is a scalable system with minimal biocontainment requirements for the inducible production of SARS-CoV-2 or other coronavirus antigens for pandemic diagnostics. 35487958 3 87 dep P. 700:701 arg1 tricornutum 703:713 tricornutum 703:713 tricornutum 703:713 Limiting phosphate and iron in growth media induced expression of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein from the P. tricornutum HASP1 promoter in the wild-type strain and in a histidine auxotrophic strain that alleviates the requirement for antibiotic selection of expression plasmids. 35285699 1 0 theme poor 270:273 arg1 response 282:289 a poor immune response 268:289 a poor immune response to the virus and low vaccine efficacy 268:327 Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. 35285699 11 1 theme genomic 2236:2242 arg1 changes 2244:2250 genomic changes 2236:2250 genomic changes 2236:2250 Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. 35285699 4 2 theme viable 640:645 arg1 virus 657:661 morphologically unaltered viable influenza virus 614:661 morphologically unaltered viable influenza virus 614:661 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 10 3 theme functional 2073:2082 arg1 differences 2084:2094 functional differences 2073:2094 functional differences that are not reflected by their genomic sequence 2073:2143 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 9 4 theme altered 1799:1805 arg1 biology 1807:1813 the altered biology 1795:1813 the altered biology 1795:1813 Since influenza viruses that infect such people do not show consistent genomic variations, it is generally assumed that the altered biology is mainly related to host factors. 35285699 9 4 theme altered 1799:1805 arg1 related 1825:1831 related 1825:1831 related 1825:1831 Since influenza viruses that infect such people do not show consistent genomic variations, it is generally assumed that the altered biology is mainly related to host factors. 35285699 4 5 theme site 726:729 arg1 occupancy 731:739 site occupancy 726:739 site occupancy 726:739 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 7 6 theme cellular 1239:1246 arg1 glycosylation 1248:1260 aberrant cellular glycosylation 1230:1260 aberrant cellular glycosylation 1230:1260 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 10 7 theme host 1865:1868 arg1 cells 1870:1874 host cells 1865:1874 host cells 1865:1874 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 11 8 dep changes 2244:2250 arg1 leading 2253:2259 leading 2253:2259 leading to reduced innate and adaptive host immune responses to infection 2253:2325 Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. 35285699 11 9 theme imbalanced 2165:2174 arg1 glycosylation 2185:2197 imbalanced cellular glycosylation 2165:2197 imbalanced cellular glycosylation 2165:2197 Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. 35285699 1 10 theme cellular 197:204 arg1 glycosylation 206:218 cellular glycosylation 197:218 cellular glycosylation 197:218 Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. 35285699 8 11 theme IMPORTANCE 1409:1418 arg1 People 1420:1425 IMPORTANCE People 1409:1425 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity 1409:1497 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 4 12 from changes 699:705 arg1 proteins 781:788 the hemagglutinin and neuraminidase proteins 745:788 the hemagglutinin and neuraminidase proteins 745:788 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 5 13 theme respiratory 921:931 arg1 collectin 939:947 an important innate immunity respiratory tract collectin 892:947 an important innate immunity respiratory tract collectin 892:947 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 5 13 theme respiratory 921:931 arg1 D 889:889 surfactant protein D 870:889 surfactant protein D (an important innate immunity respiratory tract collectin) 870:948 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 9 14 theme host 1836:1839 arg1 factors 1841:1847 host factors 1836:1847 host factors 1836:1847 Since influenza viruses that infect such people do not show consistent genomic variations, it is generally assumed that the altered biology is mainly related to host factors. 35285699 8 15 theme influenza 1586:1594 arg1 disease 1596:1602 more severe influenza disease 1574:1602 more severe influenza disease 1574:1602 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 10 16 theme genomic 2128:2134 arg1 sequence 2136:2143 their genomic sequence 2122:2143 their genomic sequence 2122:2143 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 11 17 theme adaptive 2283:2290 arg1 responses 2304:2312 reduced innate and adaptive host immune responses 2264:2312 reduced innate and adaptive host immune responses to infection 2264:2325 Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. 35285699 1 18 theme severe 237:242 arg1 disease 254:260 severe influenza disease 237:260 severe influenza disease 237:260 Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. 35285699 3 19 link N-linked 487:494 arg1 glycosylation 496:508 aberrant N-linked glycosylation 478:508 aberrant N-linked glycosylation 478:508 We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. 35285699 0 20 theme Glycome 144:150 arg1 Modification 118:129 Modification 118:129 Modification of the Viral Glycome 118:150 Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome. 35285699 10 21 theme virus 1923:1927 arg1 hemagglutinin 1929:1941 influenza virus hemagglutinin 1913:1941 influenza virus hemagglutinin 1913:1941 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 8 22 theme reduced 1607:1613 arg1 response 1622:1629 a reduced immune response 1605:1629 a reduced immune response to the virus 1605:1642 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 6 23 theme antibody 1142:1149 arg1 titers 1120:1125 antihemagglutinin and antineuraminidase titers 1080:1125 antihemagglutinin and antineuraminidase titers of total serum antibody 1080:1149 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 8 24 theme autoimmune 1458:1467 arg1 disease 1469:1475 autoimmune disease 1458:1475 autoimmune disease 1458:1475 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 0 25 theme Influenza 60:68 arg1 Viruses 70:76 Influenza Viruses 60:76 Influenza Viruses 60:76 Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome. 35285699 11 26 theme host 2292:2295 arg1 responses 2304:2312 reduced innate and adaptive host immune responses 2264:2312 reduced innate and adaptive host immune responses to infection 2264:2325 Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. 35285699 6 27 theme total 1130:1134 arg1 antibody 1142:1149 total serum antibody 1130:1149 total serum antibody 1130:1149 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 12 28 theme increased 2395:2403 arg1 risk 2405:2408 increased risk 2395:2408 increased risk of severe influenza 2395:2428 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 12 29 theme influenza 2420:2428 arg1 efficacy 2466:2473 reduced influenza virus vaccine efficacy 2434:2473 reduced influenza virus vaccine efficacy 2434:2473 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 12 29 theme influenza 2420:2428 arg1 risk 2405:2408 increased risk 2395:2408 increased risk of severe influenza 2395:2428 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 7 30 theme influenza 1361:1369 arg1 viruses 1371:1377 glycome-modified influenza viruses 1344:1377 glycome-modified influenza viruses 1344:1377 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 5 31 theme normal 987:992 arg1 occupancy 1001:1009 normal glycan occupancy 987:1009 normal glycan occupancy 987:1009 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 12 32 theme reduced 2434:2440 arg1 efficacy 2466:2473 reduced influenza virus vaccine efficacy 2434:2473 reduced influenza virus vaccine efficacy 2434:2473 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 7 33 theme glycome-modified 1344:1359 arg1 viruses 1371:1377 glycome-modified influenza viruses 1344:1377 glycome-modified influenza viruses 1344:1377 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 12 34 theme metabolic 2346:2354 arg1 dysregulation 2356:2368 metabolic dysregulation 2346:2368 metabolic dysregulation of host glycosylation 2346:2390 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 0 35 theme Host 88:91 arg1 Responses 100:108 Escape Host Immune Responses 81:108 Escape Host Immune Responses 81:108 Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome. 35285699 9 36 theme influenza 1681:1689 arg1 viruses 1691:1697 influenza viruses 1681:1697 influenza viruses that infect such people 1681:1721 Since influenza viruses that infect such people do not show consistent genomic variations, it is generally assumed that the altered biology is mainly related to host factors. 35285699 8 37 theme reduced 1649:1655 arg1 efficacy 1665:1672 reduced vaccine efficacy 1649:1672 reduced vaccine efficacy 1649:1672 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 5 38 with Hemagglutinin 791:803 arg1 occupancy 825:833 reduced glycan occupancy 810:833 reduced glycan occupancy 810:833 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 7 39 theme increased 1323:1331 arg1 ability 1333:1339 the increased ability 1319:1339 the increased ability of glycome-modified influenza viruses to evade the immune response 1319:1406 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 11 40 theme cellular 2176:2183 arg1 glycosylation 2185:2197 imbalanced cellular glycosylation 2165:2197 imbalanced cellular glycosylation 2165:2197 Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. 35285699 11 41 theme immune 2297:2302 arg1 responses 2304:2312 reduced innate and adaptive host immune responses 2264:2312 reduced innate and adaptive host immune responses to infection 2264:2325 Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. 35285699 0 42 theme Viruses 70:76 arg1 Ability 49:55 the Ability 45:55 the Ability of Influenza Viruses to Escape Host Immune Responses 45:108 Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome. 35285699 2 43 theme glycosylation 389:401 arg1 consequences 355:366 the consequences 351:366 the consequences of aberrant cellular glycosylation for the glycome 351:417 Here, we investigate the consequences of aberrant cellular glycosylation for the glycome and the biology of influenza virus. 35285699 2 43 theme glycosylation 389:401 arg1 biology 427:433 the biology 423:433 the biology of influenza virus 423:452 Here, we investigate the consequences of aberrant cellular glycosylation for the glycome and the biology of influenza virus. 35285699 0 44 theme Aberrant 0:7 arg1 Glycosylation 18:30 Aberrant Cellular Glycosylation 0:30 Aberrant Cellular Glycosylation 0:30 Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome. 35285699 9 45 theme such 1711:1714 arg1 people 1716:1721 such people 1711:1721 such people 1711:1721 Since influenza viruses that infect such people do not show consistent genomic variations, it is generally assumed that the altered biology is mainly related to host factors. 35285699 2 46 theme influenza 438:446 arg1 virus 448:452 influenza virus 438:452 influenza virus 438:452 Here, we investigate the consequences of aberrant cellular glycosylation for the glycome and the biology of influenza virus. 35285699 3 47 gly glycosylation 496:508 arg1 cells 522:526 cultured cells 513:526 cultured cells with an oligosaccharyltransferase inhibitor, NGI-1 513:577 We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. 35285699 5 48 theme innate 905:910 arg1 immunity 912:919 an important innate immunity 892:919 an important innate immunity respiratory tract collectin 892:947 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 6 49 theme protective 1177:1186 arg1 responses 1197:1205 hemagglutinin protective antibody responses 1163:1205 hemagglutinin protective antibody responses 1163:1205 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 10 50 dep have 2068:2071 arg1 may 2064:2066 may 2064:2066 may 2064:2066 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 8 51 theme cellular 1537:1544 arg1 glycosylation 1546:1558 cellular glycosylation 1537:1558 cellular glycosylation 1537:1558 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 5 52 theme surfactant 870:879 arg1 collectin 939:947 an important innate immunity respiratory tract collectin 892:947 an important innate immunity respiratory tract collectin 892:947 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 5 52 theme surfactant 870:879 arg1 D 889:889 surfactant protein D 870:889 surfactant protein D (an important innate immunity respiratory tract collectin) 870:948 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 1 53 theme low 308:310 arg1 efficacy 320:327 low vaccine efficacy 308:327 low vaccine efficacy 308:327 Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. 35285699 7 54 theme influenza 1294:1302 arg1 risk 1279:1282 the risk 1275:1282 the risk of severe influenza 1275:1302 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 7 54 theme influenza 1294:1302 arg1 result 1309:1314 a result 1307:1314 a result of the increased ability of glycome-modified influenza viruses to evade the immune response 1307:1406 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 5 55 theme D 889:889 arg1 concentration 853:865 a higher concentration 844:865 a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) 844:948 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 9 56 theme genomic 1746:1752 arg1 variations 1754:1763 consistent genomic variations 1735:1763 consistent genomic variations 1735:1763 Since influenza viruses that infect such people do not show consistent genomic variations, it is generally assumed that the altered biology is mainly related to host factors. 35285699 3 57 theme N-linked 487:494 arg1 glycosylation 496:508 aberrant N-linked glycosylation 478:508 aberrant N-linked glycosylation 478:508 We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. 35285699 1 58 theme influenza 244:252 arg1 disease 254:260 severe influenza disease 237:260 severe influenza disease 237:260 Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. 35285699 10 59 with interactions 1997:2008 arg1 system 2044:2049 the immune system 2033:2049 the immune system 2033:2049 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 4 60 theme influenza 647:655 arg1 virus 657:661 morphologically unaltered viable influenza virus 614:661 morphologically unaltered viable influenza virus 614:661 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 8 61 theme severe 1579:1584 arg1 disease 1596:1602 more severe influenza disease 1574:1602 more severe influenza disease 1574:1602 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 2 62 theme aberrant 371:378 arg1 glycosylation 389:401 aberrant cellular glycosylation 371:401 aberrant cellular glycosylation for the glycome 371:417 Here, we investigate the consequences of aberrant cellular glycosylation for the glycome and the biology of influenza virus. 35285699 4 63 dep reduced 718:724 arg1 primarily 708:716 primarily 708:716 primarily 708:716 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 5 64 theme higher 846:851 arg1 concentration 853:865 a higher concentration 844:865 a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) 844:948 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 3 65 with cells 522:526 arg1 NGI-1 573:577 NGI-1 573:577 NGI-1 573:577 We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. 35285699 3 65 with cells 522:526 arg1 inhibitor 562:570 an oligosaccharyltransferase inhibitor 533:570 an oligosaccharyltransferase inhibitor 533:570 We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. 35285699 11 66 theme innate 2272:2277 arg1 responses 2304:2312 reduced innate and adaptive host immune responses 2264:2312 reduced innate and adaptive host immune responses to infection 2264:2325 Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. 35285699 10 67 theme immune 2037:2042 arg1 system 2044:2049 the immune system 2033:2049 the immune system 2033:2049 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 9 68 theme consistent 1735:1744 arg1 variations 1754:1763 consistent genomic variations 1735:1763 consistent genomic variations 1735:1763 Since influenza viruses that infect such people do not show consistent genomic variations, it is generally assumed that the altered biology is mainly related to host factors. 35285699 1 69 theme immune 275:280 arg1 response 282:289 a poor immune response 268:289 a poor immune response to the virus and low vaccine efficacy 268:327 Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. 35285699 4 70 theme unaltered 630:638 arg1 virus 657:661 morphologically unaltered viable influenza virus 614:661 morphologically unaltered viable influenza virus 614:661 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 8 71 with People 1420:1425 arg1 disorders 1432:1440 disorders 1432:1440 disorders such as cancer, autoimmune disease, diabetes, or obesity 1432:1497 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 8 71 with People 1420:1425 arg1 cancer 1450:1455 cancer 1450:1455 cancer 1450:1455 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 8 71 with People 1420:1425 arg1 disease 1469:1475 autoimmune disease 1458:1475 autoimmune disease 1458:1475 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 8 71 with People 1420:1425 arg1 diabetes 1478:1485 diabetes 1478:1485 diabetes 1478:1485 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 8 71 with People 1420:1425 arg1 obesity 1491:1497 obesity 1491:1497 obesity 1491:1497 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 7 72 theme aberrant 1230:1237 arg1 glycosylation 1248:1260 aberrant cellular glycosylation 1230:1260 aberrant cellular glycosylation 1230:1260 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 1 73 theme metabolic 170:178 arg1 dysregulation 180:192 metabolic dysregulation 170:192 metabolic dysregulation of cellular glycosylation 170:218 Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. 35285699 10 74 theme influenza 1913:1921 arg1 hemagglutinin 1929:1941 influenza virus hemagglutinin 1913:1941 influenza virus hemagglutinin 1913:1941 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 6 75 theme antihemagglutinin 1080:1096 arg1 titers 1120:1125 antihemagglutinin and antineuraminidase titers 1080:1125 antihemagglutinin and antineuraminidase titers of total serum antibody 1080:1149 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 11 76 theme reduced 2264:2270 arg1 responses 2304:2312 reduced innate and adaptive host immune responses 2264:2312 reduced innate and adaptive host immune responses to infection 2264:2325 Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. 35285699 1 77 theme glycosylation 206:218 arg1 dysregulation 180:192 metabolic dysregulation 170:192 metabolic dysregulation of cellular glycosylation 170:218 Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. 35285699 10 78 contain have 2068:2071 arg2 differences 2084:2094 functional differences 2073:2094 functional differences that are not reflected by their genomic sequence 2073:2143 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 10 78 contain have 2068:2071 arg1 viruses 2056:2062 the viruses 2052:2062 the viruses 2052:2062 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 4 79 theme glycosylation 685:697 arg1 changes 699:705 sequence-neutral glycosylation changes 668:705 sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins 668:788 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 0 80 theme Viral 138:142 arg1 Glycome 144:150 the Viral Glycome 134:150 the Viral Glycome 134:150 Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome. 35285699 10 81 theme neuraminidase 1947:1959 arg1 glycosylation 1896:1908 glycosylation 1896:1908 glycosylation of influenza virus hemagglutinin and neuraminidase 1896:1959 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 5 82 theme tract 933:937 arg1 collectin 939:947 an important innate immunity respiratory tract collectin 892:947 an important innate immunity respiratory tract collectin 892:947 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 5 82 theme tract 933:937 arg1 D 889:889 surfactant protein D 870:889 surfactant protein D (an important innate immunity respiratory tract collectin) 870:948 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 6 83 theme NGI-1-treated 1038:1050 arg1 virus 1052:1056 NGI-1-treated virus 1038:1056 NGI-1-treated virus 1038:1056 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 7 84 theme ability 1333:1339 arg1 risk 1279:1282 the risk 1275:1282 the risk of severe influenza 1275:1302 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 7 84 theme ability 1333:1339 arg1 result 1309:1314 a result 1307:1314 a result of the increased ability of glycome-modified influenza viruses to evade the immune response 1307:1406 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 10 85 theme hemagglutinin 1929:1941 arg1 glycosylation 1896:1908 glycosylation 1896:1908 glycosylation of influenza virus hemagglutinin and neuraminidase 1896:1959 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 5 86 theme glycan 994:999 arg1 occupancy 1001:1009 normal glycan occupancy 987:1009 normal glycan occupancy 987:1009 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 6 87 theme mice 1028:1031 arg1 Immunization 1012:1023 Immunization 1012:1023 Immunization of mice with NGI-1-treated virus 1012:1056 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 8 88 theme immune 1615:1620 arg1 response 1622:1629 a reduced immune response 1605:1629 a reduced immune response to the virus 1605:1642 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 4 89 theme neuraminidase 767:779 arg1 proteins 781:788 the hemagglutinin and neuraminidase proteins 745:788 the hemagglutinin and neuraminidase proteins 745:788 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 11 90 theme viral 2214:2218 arg1 glycome 2220:2226 the viral glycome 2210:2226 the viral glycome 2210:2226 Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. 35285699 12 91 theme host 2373:2376 arg1 glycosylation 2378:2390 host glycosylation 2373:2390 host glycosylation 2373:2390 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 7 92 theme viruses 1371:1377 arg1 ability 1333:1339 the increased ability 1319:1339 the increased ability of glycome-modified influenza viruses to evade the immune response 1319:1406 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 5 93 theme immunity 912:919 arg1 collectin 939:947 an important innate immunity respiratory tract collectin 892:947 an important innate immunity respiratory tract collectin 892:947 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 5 93 theme immunity 912:919 arg1 D 889:889 surfactant protein D 870:889 surfactant protein D (an important innate immunity respiratory tract collectin) 870:948 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 6 94 theme serum 1136:1140 arg1 antibody 1142:1149 total serum antibody 1130:1149 total serum antibody 1130:1149 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 10 95 gly glycosylation 1966:1978 arg1 proteins 2019:2026 these proteins 2013:2026 these proteins 2013:2026 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 5 96 theme reduced 810:816 arg1 occupancy 825:833 reduced glycan occupancy 810:833 reduced glycan occupancy 810:833 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 0 97 theme Escape 81:86 arg1 Responses 100:108 Escape Host Immune Responses 81:108 Escape Host Immune Responses 81:108 Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome. 35285699 1 98 with Individuals 153:163 arg1 dysregulation 180:192 metabolic dysregulation 170:192 metabolic dysregulation of cellular glycosylation 170:218 Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. 35285699 8 99 contain have 1505:1508 arg2 dysregulation 1520:1532 metabolic dysregulation 1510:1532 metabolic dysregulation of cellular glycosylation 1510:1558 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 8 99 contain have 1505:1508 arg1 People 1420:1425 IMPORTANCE People 1409:1425 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity 1409:1497 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 12 100 theme influenza 2442:2450 arg1 efficacy 2466:2473 reduced influenza virus vaccine efficacy 2434:2473 reduced influenza virus vaccine efficacy 2434:2473 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 4 101 theme hemagglutinin 749:761 arg1 proteins 781:788 the hemagglutinin and neuraminidase proteins 745:788 the hemagglutinin and neuraminidase proteins 745:788 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 0 102 theme Immune 93:98 arg1 Responses 100:108 Escape Host Immune Responses 81:108 Escape Host Immune Responses 81:108 Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome. 35285699 6 103 theme antineuraminidase 1102:1118 arg1 titers 1120:1125 antihemagglutinin and antineuraminidase titers 1080:1125 antihemagglutinin and antineuraminidase titers of total serum antibody 1080:1149 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 12 104 attach link 2341:2344 arg1 efficacy 2466:2473 reduced influenza virus vaccine efficacy 2434:2473 reduced influenza virus vaccine efficacy 2434:2473 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 12 104 attach link 2341:2344 arg2 findings 2332:2339 Our findings 2328:2339 Our findings 2328:2339 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 12 104 attach link 2341:2344 arg1 risk 2405:2408 increased risk 2395:2408 increased risk of severe influenza 2395:2428 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 8 105 theme vaccine 1657:1663 arg1 efficacy 1665:1672 reduced vaccine efficacy 1649:1672 reduced vaccine efficacy 1649:1672 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 5 106 theme glycan 818:823 arg1 occupancy 825:833 reduced glycan occupancy 810:833 reduced glycan occupancy 810:833 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 12 107 theme severe 2413:2418 arg1 influenza 2420:2428 severe influenza 2413:2428 severe influenza 2413:2428 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 12 108 theme glycosylation 2378:2390 arg1 dysregulation 2356:2368 metabolic dysregulation 2346:2368 metabolic dysregulation of host glycosylation 2346:2390 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 0 109 theme Cellular 9:16 arg1 Glycosylation 18:30 Aberrant Cellular Glycosylation 0:30 Aberrant Cellular Glycosylation 0:30 Aberrant Cellular Glycosylation May Increase the Ability of Influenza Viruses to Escape Host Immune Responses through Modification of the Viral Glycome. 35285699 12 110 theme virus 2452:2456 arg1 efficacy 2466:2473 reduced influenza virus vaccine efficacy 2434:2473 reduced influenza virus vaccine efficacy 2434:2473 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 2 111 theme virus 448:452 arg1 consequences 355:366 the consequences 351:366 the consequences of aberrant cellular glycosylation for the glycome 351:417 Here, we investigate the consequences of aberrant cellular glycosylation for the glycome and the biology of influenza virus. 35285699 2 111 theme virus 448:452 arg1 biology 427:433 the biology 423:433 the biology of influenza virus 423:452 Here, we investigate the consequences of aberrant cellular glycosylation for the glycome and the biology of influenza virus. 35285699 2 112 theme cellular 380:387 arg1 glycosylation 389:401 aberrant cellular glycosylation 371:401 aberrant cellular glycosylation for the glycome 371:417 Here, we investigate the consequences of aberrant cellular glycosylation for the glycome and the biology of influenza virus. 35285699 5 113 theme important 895:903 arg1 immunity 912:919 an important innate immunity 892:919 an important innate immunity respiratory tract collectin 892:947 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 6 114 theme antibody 1188:1195 arg1 responses 1197:1205 hemagglutinin protective antibody responses 1163:1205 hemagglutinin protective antibody responses 1163:1205 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 8 115 contain have 1569:1572 arg2 response 1622:1629 a reduced immune response 1605:1629 a reduced immune response to the virus 1605:1642 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 8 115 contain have 1569:1572 arg1 People 1420:1425 IMPORTANCE People 1409:1425 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity 1409:1497 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 8 115 contain have 1569:1572 arg2 disease 1596:1602 more severe influenza disease 1574:1602 more severe influenza disease 1574:1602 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 8 115 contain have 1569:1572 arg2 efficacy 1665:1672 reduced vaccine efficacy 1649:1672 reduced vaccine efficacy 1649:1672 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 8 116 theme metabolic 1510:1518 arg1 dysregulation 1520:1532 metabolic dysregulation 1510:1532 metabolic dysregulation of cellular glycosylation 1510:1558 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 3 117 theme aberrant 478:485 arg1 glycosylation 496:508 aberrant N-linked glycosylation 478:508 aberrant N-linked glycosylation 478:508 We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. 35285699 7 118 theme severe 1287:1292 arg1 influenza 1294:1302 severe influenza 1287:1302 severe influenza 1287:1302 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 10 119 gly glycosylation 1896:1908 arg1 neuraminidase 1947:1959 neuraminidase 1947:1959 neuraminidase 1947:1959 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 10 119 gly glycosylation 1896:1908 arg1 hemagglutinin 1929:1941 influenza virus hemagglutinin 1913:1941 influenza virus hemagglutinin 1913:1941 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 6 120 theme hemagglutinin 1163:1175 arg1 responses 1197:1205 hemagglutinin protective antibody responses 1163:1205 hemagglutinin protective antibody responses 1163:1205 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 5 121 theme protein 881:887 arg1 collectin 939:947 an important innate immunity respiratory tract collectin 892:947 an important innate immunity respiratory tract collectin 892:947 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 5 121 theme protein 881:887 arg1 D 889:889 surfactant protein D 870:889 surfactant protein D (an important innate immunity respiratory tract collectin) 870:948 Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. 35285699 1 122 theme vaccine 312:318 arg1 efficacy 320:327 low vaccine efficacy 308:327 low vaccine efficacy 308:327 Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. 35285699 4 123 dep changes 699:705 arg1 reduced 718:724 reduced 718:724 reduced site occupancy 718:739 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 8 124 theme glycosylation 1546:1558 arg1 dysregulation 1520:1532 metabolic dysregulation 1510:1532 metabolic dysregulation of cellular glycosylation 1510:1558 IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. 35285699 3 125 theme cultured 513:520 arg1 cells 522:526 cultured cells 513:526 cultured cells with an oligosaccharyltransferase inhibitor, NGI-1 513:577 We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. 35285699 6 126 with Immunization 1012:1023 arg1 virus 1052:1056 NGI-1-treated virus 1038:1056 NGI-1-treated virus 1038:1056 Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. 35285699 10 127 theme proteins 2019:2026 arg1 interactions 1997:2008 interactions 1997:2008 interactions of these proteins with the immune system 1997:2049 However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. 35285699 12 128 theme vaccine 2458:2464 arg1 efficacy 2466:2473 reduced influenza virus vaccine efficacy 2434:2473 reduced influenza virus vaccine efficacy 2434:2473 Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy. 35285699 7 129 theme immune 1392:1397 arg1 response 1399:1406 the immune response 1388:1406 the immune response 1388:1406 Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. 35285699 4 130 theme sequence-neutral 668:683 arg1 changes 699:705 sequence-neutral glycosylation changes 668:705 sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins 668:788 Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. 35285699 3 131 theme oligosaccharyltransferase 536:560 arg1 NGI-1 573:577 NGI-1 573:577 NGI-1 573:577 We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. 35285699 3 131 theme oligosaccharyltransferase 536:560 arg1 inhibitor 562:570 an oligosaccharyltransferase inhibitor 533:570 an oligosaccharyltransferase inhibitor 533:570 We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. 37290287 0 0 theme unfolded 49:56 arg1 response 66:73 the unfolded protein response 45:73 the unfolded protein response (UPR) of plants 45:89 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 0 0 theme unfolded 49:56 arg1 UPR 76:78 UPR 76:78 UPR 76:78 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 3 1 theme response 611:618 arg1 inducer 583:589 inducer 583:589 inducer of unfolded protein response (UPR) 583:624 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 1 theme response 611:618 arg1 sensitivity 507:517 reduced sensitivity 499:517 reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation 499:577 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 6 2 from defects 997:1003 arg1 plants 1013:1018 rcn1 plants 1008:1018 rcn1 plants 1008:1018 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 3 3 theme wild-type 688:696 arg1 Col-0 715:719 Col-0 715:719 Col-0 715:719 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 3 theme wild-type 688:696 arg1 Ws-2 706:709 Ws-2 706:709 Ws-2 706:709 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 3 theme wild-type 688:696 arg1 plants 698:703 wild-type plants 688:703 wild-type plants (Ws-2 and Col-0) 688:720 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 2 4 theme ACID1 389:393 arg1 CURL 362:365 ROOTS CURL 356:365 ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A 356:453 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 0 5 from role 4:7 arg1 response 66:73 the unfolded protein response 45:73 the unfolded protein response (UPR) of plants 45:89 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 0 5 from role 4:7 arg1 UPR 76:78 UPR 76:78 UPR 76:78 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 3 6 dep mutants 461:467 arg1 rcn1-2 481:486 rcn1-2 481:486 rcn1-2 481:486 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 6 dep mutants 461:467 arg1 rcn1-1 470:475 rcn1-1 470:475 rcn1-1 470:475 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 6 dep mutants 461:467 arg1 mutants 461:467 RCN1 mutants 456:467 RCN1 mutants (rcn1-1 and rcn1-2) 456:487 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 6 7 from inhibition 1053:1062 arg1 plants 1082:1087 Ws-2 and Col-0 plants 1067:1087 Ws-2 and Col-0 plants 1067:1087 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 2 8 theme A1 416:417 arg1 ACID1 389:393 NAPHTHYLPHTHALAMIC ACID1 370:393 NAPHTHYLPHTHALAMIC ACID1 (RCN1) 370:400 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 2 8 theme A1 416:417 arg1 isoform 427:433 a regulatory A1 subunit isoform 403:433 a regulatory A1 subunit isoform of Arabidopsis PP2A 403:453 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 3 9 theme N-linked 556:563 arg1 glycosylation 565:577 N-linked glycosylation 556:577 N-linked glycosylation 556:577 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 6 10 theme growth 990:995 arg1 defects 997:1003 Cantharidin, a PP2A inhibitor, exacerbated growth defects 947:1003 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants 947:1018 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 0 11 theme protein 58:64 arg1 response 66:73 the unfolded protein response 45:73 the unfolded protein response (UPR) of plants 45:89 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 0 11 theme protein 58:64 arg1 UPR 76:78 UPR 76:78 UPR 76:78 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 3 12 theme unfolded 594:601 arg1 UPR 621:623 UPR 621:623 UPR 621:623 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 12 theme unfolded 594:601 arg1 response 611:618 unfolded protein response 594:618 unfolded protein response (UPR) 594:624 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 6 13 theme Col-0 1076:1080 arg1 plants 1082:1087 Ws-2 and Col-0 plants 1067:1087 Ws-2 and Col-0 plants 1067:1087 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 6 14 theme exacerbated 978:988 arg1 defects 997:1003 Cantharidin, a PP2A inhibitor, exacerbated growth defects 947:1003 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants 947:1018 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 4 15 theme rcn1-2 809:814 arg1 plants 816:821 rcn1-2 plants 809:821 rcn1-2 plants 809:821 TM negatively impacted PP2A activity in Col-0 plants but did not significantly affect rcn1-2 plants. 37290287 3 16 theme protein 603:609 arg1 UPR 621:623 UPR 621:623 UPR 621:623 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 16 theme protein 603:609 arg1 response 611:618 unfolded protein response 594:618 unfolded protein response (UPR) 594:624 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 6 17 theme rcn1 1008:1011 arg1 plants 1013:1018 rcn1 plants 1008:1018 rcn1 plants 1008:1018 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 2 18 theme NAPHTHYLPHTHALAMIC 370:387 arg1 RCN1 396:399 RCN1 396:399 RCN1 396:399 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 2 18 theme NAPHTHYLPHTHALAMIC 370:387 arg1 ACID1 389:393 NAPHTHYLPHTHALAMIC ACID1 370:393 NAPHTHYLPHTHALAMIC ACID1 (RCN1) 370:400 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 2 18 theme NAPHTHYLPHTHALAMIC 370:387 arg1 isoform 427:433 a regulatory A1 subunit isoform 403:433 a regulatory A1 subunit isoform of Arabidopsis PP2A 403:453 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 3 19 theme gene 626:629 arg1 expression 631:640 gene expression 626:640 gene expression 626:640 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 5 20 theme genes 924:928 arg1 levels 887:892 the transcription levels 869:892 the transcription levels of the PP2AA1(RCN1), 2, and 3 genes in Col-0 plants 869:944 Additionally, TM treatment did not influence the transcription levels of the PP2AA1(RCN1), 2, and 3 genes in Col-0 plants. 37290287 3 21 theme RCN1 456:459 arg1 rcn1-2 481:486 rcn1-2 481:486 rcn1-2 481:486 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 21 theme RCN1 456:459 arg1 rcn1-1 470:475 rcn1-1 470:475 rcn1-1 470:475 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 21 theme RCN1 456:459 arg1 mutants 461:467 RCN1 mutants 456:467 RCN1 mutants (rcn1-1 and rcn1-2) 456:487 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 7 22 theme TM 1135:1136 arg1 hypersensitivity 1138:1153 TM hypersensitivity 1135:1153 TM hypersensitivity in ire1a&b and bzip28&60 mutants 1135:1186 Furthermore, cantharidin treatment mitigated TM hypersensitivity in ire1a&b and bzip28&60 mutants. 37290287 3 23 dep plants 698:703 arg1 Col-0 715:719 Col-0 715:719 Col-0 715:719 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 23 dep plants 698:703 arg1 Ws-2 706:709 Ws-2 706:709 Ws-2 706:709 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 23 dep plants 698:703 arg1 plants 698:703 wild-type plants 688:703 wild-type plants (Ws-2 and Col-0) 688:720 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 8 24 from UPR 1261:1263 arg1 Arabidopsis 1268:1278 Arabidopsis 1268:1278 Arabidopsis 1268:1278 These findings suggest that PP2A activity is essential for an efficient UPR in Arabidopsis. 37290287 0 25 theme protein 12:18 arg1 2A 32:33 protein phosphatase 2A 12:33 protein phosphatase 2A (PP2A) 12:40 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 0 25 theme protein 12:18 arg1 PP2A 36:39 PP2A 36:39 PP2A 36:39 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 1 26 theme endoplasmic 194:204 arg1 reticulum 206:214 endoplasmic reticulum 194:214 the endoplasmic reticulum (ER) stress response 190:235 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 1 26 theme endoplasmic 194:204 arg1 ER 217:218 ER 217:218 ER 217:218 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 2 27 theme Arabidopsis 438:448 arg1 PP2A 450:453 Arabidopsis PP2A 438:453 Arabidopsis PP2A 438:453 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 3 28 link N-linked 556:563 arg1 glycosylation 565:577 N-linked glycosylation 556:577 N-linked glycosylation 556:577 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 1 29 theme key 127:129 arg1 regulator 131:139 a key regulator 125:139 a key regulator of plant growth and development 125:171 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 1 29 theme key 127:129 arg1 2A 112:113 Protein phosphatase 2A 92:113 Protein phosphatase 2A (PP2A) 92:120 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 1 30 theme reticulum 206:214 arg1 response 228:235 the endoplasmic reticulum (ER) stress response 190:235 the endoplasmic reticulum (ER) stress response 190:235 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 4 31 theme Col-0 763:767 arg1 plants 769:774 Col-0 plants 763:774 Col-0 plants 763:774 TM negatively impacted PP2A activity in Col-0 plants but did not significantly affect rcn1-2 plants. 37290287 8 32 theme PP2A 1217:1220 arg1 activity 1222:1229 PP2A activity 1217:1229 PP2A activity 1217:1229 These findings suggest that PP2A activity is essential for an efficient UPR in Arabidopsis. 37290287 6 33 theme Cantharidin 947:957 arg1 defects 997:1003 Cantharidin, a PP2A inhibitor, exacerbated growth defects 947:1003 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants 947:1018 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 2 34 theme ER 312:313 arg1 stress 315:320 ER stress 312:320 ER stress 312:320 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 0 35 theme 2A 32:33 arg1 role 4:7 The role 0:7 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants 0:89 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 7 36 theme cantharidin 1103:1113 arg1 treatment 1115:1123 cantharidin treatment 1103:1123 cantharidin treatment 1103:1123 Furthermore, cantharidin treatment mitigated TM hypersensitivity in ire1a&b and bzip28&60 mutants. 37290287 6 37 theme growth 1046:1051 arg1 inhibition 1053:1062 TM-induced growth inhibition 1035:1062 TM-induced growth inhibition in Ws-2 and Col-0 plants 1035:1087 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 6 38 theme PP2A 962:965 arg1 Cantharidin 947:957 Cantharidin 947:957 Cantharidin 947:957 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 6 38 theme PP2A 962:965 arg1 inhibitor 967:975 a PP2A inhibitor 960:975 a PP2A inhibitor 960:975 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 0 39 theme phosphatase 20:30 arg1 2A 32:33 protein phosphatase 2A 12:33 protein phosphatase 2A (PP2A) 12:40 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 0 39 theme phosphatase 20:30 arg1 PP2A 36:39 PP2A 36:39 PP2A 36:39 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 0 40 theme plants 84:89 arg1 response 66:73 the unfolded protein response 45:73 the unfolded protein response (UPR) of plants 45:89 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 0 40 theme plants 84:89 arg1 UPR 76:78 UPR 76:78 UPR 76:78 The role of protein phosphatase 2A (PP2A) in the unfolded protein response (UPR) of plants. 37290287 2 41 theme loss-of-function 328:343 arg1 mutants 345:351 loss-of-function mutants 328:351 loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A 328:453 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 2 42 theme subunit 419:425 arg1 ACID1 389:393 NAPHTHYLPHTHALAMIC ACID1 370:393 NAPHTHYLPHTHALAMIC ACID1 (RCN1) 370:400 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 2 42 theme subunit 419:425 arg1 isoform 427:433 a regulatory A1 subunit isoform 403:433 a regulatory A1 subunit isoform of Arabidopsis PP2A 403:453 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 1 43 theme plant 144:148 arg1 regulator 131:139 a key regulator 125:139 a key regulator of plant growth and development 125:171 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 1 43 theme plant 144:148 arg1 2A 112:113 Protein phosphatase 2A 92:113 Protein phosphatase 2A (PP2A) 92:120 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 2 44 theme CURL 362:365 arg1 mutants 345:351 loss-of-function mutants 328:351 loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A 328:453 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 5 45 theme Col-0 933:937 arg1 plants 939:944 Col-0 plants 933:944 Col-0 plants 933:944 Additionally, TM treatment did not influence the transcription levels of the PP2AA1(RCN1), 2, and 3 genes in Col-0 plants. 37290287 4 46 theme PP2A 746:749 arg1 activity 751:758 PP2A activity 746:758 PP2A activity in Col-0 plants 746:774 TM negatively impacted PP2A activity in Col-0 plants but did not significantly affect rcn1-2 plants. 37290287 5 47 theme 2 915:915 arg1 PP2AA1 901:906 the PP2AA1 897:906 the PP2AA1(RCN1) 897:912 Additionally, TM treatment did not influence the transcription levels of the PP2AA1(RCN1), 2, and 3 genes in Col-0 plants. 37290287 5 47 theme 2 915:915 arg1 RCN1 908:911 RCN1 908:911 RCN1 908:911 Additionally, TM treatment did not influence the transcription levels of the PP2AA1(RCN1), 2, and 3 genes in Col-0 plants. 37290287 5 48 theme transcription 873:885 arg1 levels 887:892 the transcription levels 869:892 the transcription levels of the PP2AA1(RCN1), 2, and 3 genes in Col-0 plants 869:944 Additionally, TM treatment did not influence the transcription levels of the PP2AA1(RCN1), 2, and 3 genes in Col-0 plants. 37290287 2 49 theme ROOTS 356:360 arg1 CURL 362:365 ROOTS CURL 356:365 ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A 356:453 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 1 50 theme stress 221:226 arg1 response 228:235 the endoplasmic reticulum (ER) stress response 190:235 the endoplasmic reticulum (ER) stress response 190:235 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 1 51 from role 182:185 arg1 response 228:235 the endoplasmic reticulum (ER) stress response 190:235 the endoplasmic reticulum (ER) stress response 190:235 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 6 52 theme Ws-2 1067:1070 arg1 plants 1082:1087 Ws-2 and Col-0 plants 1067:1087 Ws-2 and Col-0 plants 1067:1087 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 8 53 theme efficient 1251:1259 arg1 UPR 1261:1263 an efficient UPR 1248:1263 an efficient UPR in Arabidopsis 1248:1278 These findings suggest that PP2A activity is essential for an efficient UPR in Arabidopsis. 37290287 4 54 from activity 751:758 arg1 plants 769:774 Col-0 plants 763:774 Col-0 plants 763:774 TM negatively impacted PP2A activity in Col-0 plants but did not significantly affect rcn1-2 plants. 37290287 3 55 theme reduced 499:505 arg1 sensitivity 507:517 reduced sensitivity 499:517 reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation 499:577 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 6 56 theme TM-induced 1035:1044 arg1 inhibition 1053:1062 TM-induced growth inhibition 1035:1062 TM-induced growth inhibition in Ws-2 and Col-0 plants 1035:1087 Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. 37290287 3 57 theme severe 661:666 arg1 effects 668:674 less severe effects 656:674 less severe effects 656:674 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 2 58 theme PP2A 450:453 arg1 ACID1 389:393 NAPHTHYLPHTHALAMIC ACID1 370:393 NAPHTHYLPHTHALAMIC ACID1 (RCN1) 370:400 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 2 58 theme PP2A 450:453 arg1 isoform 427:433 a regulatory A1 subunit isoform 403:433 a regulatory A1 subunit isoform of Arabidopsis PP2A 403:453 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 1 59 dep plant 144:148 arg1 development 161:171 development 161:171 development 161:171 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 1 59 dep plant 144:148 arg1 growth 150:155 growth 150:155 growth 150:155 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 5 60 from levels 887:892 arg1 plants 939:944 Col-0 plants 933:944 Col-0 plants 933:944 Additionally, TM treatment did not influence the transcription levels of the PP2AA1(RCN1), 2, and 3 genes in Col-0 plants. 37290287 3 61 dep sensitivity 507:517 arg1 expression 631:640 gene expression 626:640 gene expression 626:640 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 2 62 theme PP2A 301:304 arg1 function 289:296 the function 285:296 the function of PP2A 285:304 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 7 63 from hypersensitivity 1138:1153 arg1 mutants 1180:1186 ire1a&b and bzip28&60 mutants 1158:1186 mutants 1180:1186 Furthermore, cantharidin treatment mitigated TM hypersensitivity in ire1a&b and bzip28&60 mutants. 37290287 1 64 theme Protein 92:98 arg1 regulator 131:139 a key regulator 125:139 a key regulator of plant growth and development 125:171 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 1 64 theme Protein 92:98 arg1 PP2A 116:119 PP2A 116:119 PP2A 116:119 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 1 64 theme Protein 92:98 arg1 2A 112:113 Protein phosphatase 2A 92:113 Protein phosphatase 2A (PP2A) 92:120 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 7 65 theme ire1a&b 1158:1164 arg1 mutants 1180:1186 ire1a&b and bzip28&60 mutants 1158:1186 mutants 1180:1186 Furthermore, cantharidin treatment mitigated TM hypersensitivity in ire1a&b and bzip28&60 mutants. 37290287 5 66 theme TM 838:839 arg1 treatment 841:849 TM treatment 838:849 TM treatment 838:849 Additionally, TM treatment did not influence the transcription levels of the PP2AA1(RCN1), 2, and 3 genes in Col-0 plants. 37290287 3 67 theme glycosylation 565:577 arg1 tunicamycin 522:532 tunicamycin 522:532 tunicamycin (TM) 522:537 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 3 67 theme glycosylation 565:577 arg1 inhibitor 543:551 an inhibitor 540:551 an inhibitor of N-linked glycosylation 540:577 RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). 37290287 7 68 theme bzip28&60 1170:1178 arg1 mutants 1180:1186 ire1a&b and bzip28&60 mutants 1158:1186 mutants 1180:1186 Furthermore, cantharidin treatment mitigated TM hypersensitivity in ire1a&b and bzip28&60 mutants. 37290287 1 69 theme phosphatase 100:110 arg1 regulator 131:139 a key regulator 125:139 a key regulator of plant growth and development 125:171 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 1 69 theme phosphatase 100:110 arg1 PP2A 116:119 PP2A 116:119 PP2A 116:119 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 1 69 theme phosphatase 100:110 arg1 2A 112:113 Protein phosphatase 2A 92:113 Protein phosphatase 2A (PP2A) 92:120 Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. 37290287 2 70 theme regulatory 405:414 arg1 ACID1 389:393 NAPHTHYLPHTHALAMIC ACID1 370:393 NAPHTHYLPHTHALAMIC ACID1 (RCN1) 370:400 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 37290287 2 70 theme regulatory 405:414 arg1 isoform 427:433 a regulatory A1 subunit isoform 403:433 a regulatory A1 subunit isoform of Arabidopsis PP2A 403:453 In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. 36560629 7 0 theme DAF 987:989 arg1 molecules 991:999 60 DAF molecules 984:999 60 DAF molecules 984:999 Whilst 60 DAF molecules can attach to the virion in the E6 pose, no more than 30 can attach to E11 due to steric restrictions. 36560629 6 1 theme reported 875:882 arg1 complexes 894:902 reported DAF/virus complexes 875:902 reported DAF/virus complexes 875:902 DAF is a receptor for at least 20 enteroviruses and we classify its binding patterns from reported DAF/virus complexes into two distinct positions and orientations, named as E6 and E11 poses. 36560629 3 2 from ectodomain 448:457 arg1 Å 510:510 3.1 Å 506:510 3.1 Å determined by cryo-electron microscopy (cryo-EM) 506:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 8 3 theme E6 1255:1256 arg1 mode 1258:1261 the E6 mode 1251:1261 the E6 mode 1251:1261 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier. 36560629 3 4 theme E11 424:426 arg1 complex 413:419 the complex 409:419 the complex of E11 409:426 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 7 5 theme E6 1033:1034 arg1 pose 1036:1039 the E6 pose 1029:1039 the E6 pose 1029:1039 Whilst 60 DAF molecules can attach to the virion in the E6 pose, no more than 30 can attach to E11 due to steric restrictions. 36560629 8 6 theme structure 1154:1162 arg1 phylogenies 1183:1193 sequence-based phylogenies 1168:1193 sequence-based phylogenies 1168:1193 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier. 36560629 8 6 theme structure 1154:1162 arg1 modes 1129:1133 the distinct modes 1116:1133 the distinct modes of interaction and structure 1116:1162 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier. 36560629 5 7 theme BC 769:770 arg1 loop 772:775 the VP2 BC loop 761:775 the VP2 BC loop of E11 761:782 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 36560629 5 8 theme VP2 765:767 arg1 loop 772:775 the VP2 BC loop 761:775 the VP2 BC loop of E11 761:782 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 36560629 5 9 dep glycan 730:735 arg1 residue 738:744 residue 95 738:747 residue 95 of DAF 738:754 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 36560629 5 9 dep glycan 730:735 arg1 DAF 752:754 DAF 752:754 DAF 752:754 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 36560629 3 10 theme DAF 462:464 arg1 structure 396:404 the structure 392:404 the structure of the complex of E11 392:426 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 10 theme DAF 462:464 arg1 DAF 462:464 DAF 462:464 DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM) 462:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 10 theme DAF 462:464 arg1 ectodomain 448:457 the full-length ectodomain 432:457 the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM) 432:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 10 theme DAF 462:464 arg1 complex 413:419 the complex 409:419 the complex of E11 409:426 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 5 11 theme DAF 752:754 arg1 residue 738:744 residue 95 738:747 residue 95 of DAF 738:754 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 36560629 5 11 theme DAF 752:754 arg1 DAF 752:754 DAF 752:754 DAF 752:754 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 36560629 2 12 theme attachment 347:356 arg1 factor 308:313 Decay-accelerating factor 289:313 Decay-accelerating factor (DAF, also known as CD55) 289:339 Decay-accelerating factor (DAF, also known as CD55) is an attachment receptor for E11. 36560629 2 12 theme attachment 347:356 arg1 receptor 358:365 an attachment receptor 344:365 an attachment receptor for E11 344:373 Decay-accelerating factor (DAF, also known as CD55) is an attachment receptor for E11. 36560629 3 13 theme full-length 436:446 arg1 DAF 462:464 DAF 462:464 DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM) 462:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 13 theme full-length 436:446 arg1 ectodomain 448:457 the full-length ectodomain 432:457 the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM) 432:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 13 theme full-length 436:446 arg1 complex 413:419 the complex 409:419 the complex of E11 409:426 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 1 14 dep serious 247:253 arg1 neonatal 255:262 neonatal 255:262 neonatal 255:262 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 3 15 from structure 396:404 arg1 Å 510:510 3.1 Å 506:510 3.1 Å determined by cryo-electron microscopy (cryo-EM) 506:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 5 16 theme E11 780:782 arg1 glycan 730:735 the N-linked glycan 717:735 the N-linked glycan (residue 95 of DAF) 717:755 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 36560629 5 16 theme E11 780:782 arg1 loop 772:775 the VP2 BC loop 761:775 the VP2 BC loop of E11 761:782 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 36560629 4 17 dep VP2 642:644 arg1 EF 646:647 EF 646:647 EF 646:647 SCRs 3 and 4 of DAF interact with E11 at the southern rim of the canyon via the VP2 EF and VP3 BC loops. 36560629 4 17 dep VP2 642:644 arg1 loops 660:664 BC loops 657:664 BC loops 657:664 SCRs 3 and 4 of DAF interact with E11 at the southern rim of the canyon via the VP2 EF and VP3 BC loops. 36560629 3 18 theme consensus 473:481 arg1 SCRs 492:495 SCRs 492:495 SCRs 492:495 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 18 theme consensus 473:481 arg1 repeats 483:489 short consensus repeats 467:489 short consensus repeats 467:489 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 19 from Å 510:510 arg1 structure 396:404 the structure 392:404 the structure of the complex of E11 392:426 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 19 from Å 510:510 arg1 DAF 462:464 DAF 462:464 DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM) 462:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 19 from Å 510:510 arg1 ectodomain 448:457 the full-length ectodomain 432:457 the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM) 432:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 19 from Å 510:510 arg1 complex 413:419 the complex 409:419 the complex of E11 409:426 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 8 20 theme phylogenies 1183:1193 arg1 Analysis 1104:1111 Analysis 1104:1111 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies 1104:1193 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier. 36560629 0 21 theme Binding 22:28 arg1 Switching 0:8 Switching 0:8 Switching of Receptor Binding 0:28 Switching of Receptor Binding Poses between Closely Related Enteroviruses. 36560629 1 22 theme major 232:236 arg1 cause 238:242 a major cause 230:242 a major cause of serious neonatal morbidity and mortality 230:286 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 1 22 theme major 232:236 arg1 echovirus 208:216 example echovirus 11 200:219 example echovirus 11 (E11) 200:225 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 2 23 dep factor 308:313 arg1 DAF 316:318 DAF 316:318 DAF 316:318 Decay-accelerating factor (DAF, also known as CD55) is an attachment receptor for E11. 36560629 6 24 theme binding 853:859 arg1 patterns 861:868 its binding patterns 849:868 its binding patterns from reported DAF/virus complexes 849:902 DAF is a receptor for at least 20 enteroviruses and we classify its binding patterns from reported DAF/virus complexes into two distinct positions and orientations, named as E6 and E11 poses. 36560629 6 25 dep E6 959:960 arg1 poses 970:974 poses 970:974 poses 970:974 DAF is a receptor for at least 20 enteroviruses and we classify its binding patterns from reported DAF/virus complexes into two distinct positions and orientations, named as E6 and E11 poses. 36560629 0 26 theme Receptor 13:20 arg1 Binding 22:28 Receptor Binding 13:28 Receptor Binding 13:28 Switching of Receptor Binding Poses between Closely Related Enteroviruses. 36560629 4 27 theme canyon 627:632 arg1 rim 616:618 the southern rim 603:618 the southern rim of the canyon via the VP2 EF and VP3 BC loops 603:664 SCRs 3 and 4 of DAF interact with E11 at the southern rim of the canyon via the VP2 EF and VP3 BC loops. 36560629 3 28 theme cryo-electron 526:538 arg1 cryo-EM 552:558 cryo-EM 552:558 cryo-EM 552:558 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 28 theme cryo-electron 526:538 arg1 microscopy 540:549 cryo-electron microscopy 526:549 cryo-electron microscopy (cryo-EM) 526:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 29 theme short 467:471 arg1 SCRs 492:495 SCRs 492:495 SCRs 492:495 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 29 theme short 467:471 arg1 repeats 483:489 short consensus repeats 467:489 short consensus repeats 467:489 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 1 30 theme human 180:184 arg1 diseases 186:193 human diseases 180:193 human diseases 180:193 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 3 31 theme complex 413:419 arg1 structure 396:404 the structure 392:404 the structure of the complex of E11 392:426 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 31 theme complex 413:419 arg1 DAF 462:464 DAF 462:464 DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM) 462:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 31 theme complex 413:419 arg1 ectodomain 448:457 the full-length ectodomain 432:457 the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM) 432:559 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 31 theme complex 413:419 arg1 complex 413:419 the complex 409:419 the complex of E11 409:426 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 6 32 theme distinct 913:920 arg1 positions 922:930 two distinct positions 909:930 two distinct positions 909:930 DAF is a receptor for at least 20 enteroviruses and we classify its binding patterns from reported DAF/virus complexes into two distinct positions and orientations, named as E6 and E11 poses. 36560629 8 33 theme modes 1129:1133 arg1 Analysis 1104:1111 Analysis 1104:1111 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies 1104:1193 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier. 36560629 1 34 theme diseases 186:193 arg1 range 171:175 a range 169:175 a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality 169:286 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 1 35 theme serious 247:253 arg1 morbidity 264:272 serious neonatal morbidity 247:272 serious neonatal morbidity 247:272 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 5 36 link N-linked 721:728 arg1 glycan 730:735 the N-linked glycan 717:735 the N-linked glycan (residue 95 of DAF) 717:755 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 36560629 3 37 theme 1-4 498:500 arg1 SCRs 492:495 SCRs 492:495 SCRs 492:495 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 37 theme 1-4 498:500 arg1 repeats 483:489 short consensus repeats 467:489 short consensus repeats 467:489 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 0 38 theme Related 52:58 arg1 Enteroviruses 60:72 Closely Related Enteroviruses 44:72 Closely Related Enteroviruses 44:72 Switching of Receptor Binding Poses between Closely Related Enteroviruses. 36560629 8 39 theme interaction 1138:1148 arg1 phylogenies 1183:1193 sequence-based phylogenies 1168:1193 sequence-based phylogenies 1168:1193 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier. 36560629 8 39 theme interaction 1138:1148 arg1 modes 1129:1133 the distinct modes 1116:1133 the distinct modes of interaction and structure 1116:1162 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier. 36560629 4 40 theme DAF 578:580 arg1 SCRs 562:565 SCRs 3 and 4 562:573 SCRs 3 and 4 of DAF 562:580 SCRs 3 and 4 of DAF interact with E11 at the southern rim of the canyon via the VP2 EF and VP3 BC loops. 36560629 1 41 theme morbidity 264:272 arg1 cause 238:242 a major cause 230:242 a major cause of serious neonatal morbidity and mortality 230:286 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 1 41 theme morbidity 264:272 arg1 echovirus 208:216 example echovirus 11 200:219 example echovirus 11 (E11) 200:225 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 4 42 theme BC 657:658 arg1 loops 660:664 BC loops 657:664 BC loops 657:664 SCRs 3 and 4 of DAF interact with E11 at the southern rim of the canyon via the VP2 EF and VP3 BC loops. 36560629 2 43 theme Decay-accelerating 289:306 arg1 factor 308:313 Decay-accelerating factor 289:313 Decay-accelerating factor (DAF, also known as CD55) 289:339 Decay-accelerating factor (DAF, also known as CD55) is an attachment receptor for E11. 36560629 2 43 theme Decay-accelerating 289:306 arg1 receptor 358:365 an attachment receptor 344:365 an attachment receptor for E11 344:373 Decay-accelerating factor (DAF, also known as CD55) is an attachment receptor for E11. 36560629 7 44 theme steric 1083:1088 arg1 restrictions 1090:1101 steric restrictions 1083:1101 steric restrictions 1083:1101 Whilst 60 DAF molecules can attach to the virion in the E6 pose, no more than 30 can attach to E11 due to steric restrictions. 36560629 1 45 dep diseases 186:193 arg1 cause 238:242 a major cause 230:242 a major cause of serious neonatal morbidity and mortality 230:286 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 1 45 dep diseases 186:193 arg1 echovirus 208:216 example echovirus 11 200:219 example echovirus 11 (E11) 200:225 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 8 46 theme distinct 1120:1127 arg1 modes 1129:1133 the distinct modes 1116:1133 the distinct modes of interaction and structure 1116:1162 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier. 36560629 1 47 theme approved 121:128 arg1 vaccines 130:137 no approved vaccines 118:137 no approved vaccines 118:137 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 4 48 theme southern 607:614 arg1 rim 616:618 the southern rim 603:618 the southern rim of the canyon via the VP2 EF and VP3 BC loops 603:664 SCRs 3 and 4 of DAF interact with E11 at the southern rim of the canyon via the VP2 EF and VP3 BC loops. 36560629 7 49 attach attach 1062:1067 arg2 more 1045:1048 more 1045:1048 more 1045:1048 Whilst 60 DAF molecules can attach to the virion in the E6 pose, no more than 30 can attach to E11 due to steric restrictions. 36560629 7 49 attach attach 1062:1067 arg1 E11 1072:1074 E11 1072:1074 E11 1072:1074 Whilst 60 DAF molecules can attach to the virion in the E6 pose, no more than 30 can attach to E11 due to steric restrictions. 36560629 7 50 attach attach 1005:1010 arg1 virion 1019:1024 the virion 1015:1024 the virion 1015:1024 Whilst 60 DAF molecules can attach to the virion in the E6 pose, no more than 30 can attach to E11 due to steric restrictions. 36560629 7 50 attach attach 1005:1010 arg2 molecules 991:999 60 DAF molecules 984:999 60 DAF molecules 984:999 Whilst 60 DAF molecules can attach to the virion in the E6 pose, no more than 30 can attach to E11 due to steric restrictions. 36560629 3 51 dep DAF 462:464 arg1 SCRs 492:495 SCRs 492:495 SCRs 492:495 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 3 51 dep DAF 462:464 arg1 repeats 483:489 short consensus repeats 467:489 short consensus repeats 467:489 Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). 36560629 1 52 theme example 200:206 arg1 echovirus 208:216 example echovirus 11 200:219 example echovirus 11 (E11) 200:225 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 1 52 theme example 200:206 arg1 cause 238:242 a major cause 230:242 a major cause of serious neonatal morbidity and mortality 230:286 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 1 52 theme example 200:206 arg1 E11 222:224 E11 222:224 E11 222:224 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 6 53 theme DAF/virus 884:892 arg1 complexes 894:902 reported DAF/virus complexes 875:902 reported DAF/virus complexes 875:902 DAF is a receptor for at least 20 enteroviruses and we classify its binding patterns from reported DAF/virus complexes into two distinct positions and orientations, named as E6 and E11 poses. 36560629 8 54 theme sequence-based 1168:1181 arg1 phylogenies 1183:1193 sequence-based phylogenies 1168:1193 sequence-based phylogenies 1168:1193 Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier. 36560629 5 55 theme unexpected 686:695 arg1 interaction 697:707 an unexpected interaction 683:707 an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11 683:782 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 36560629 1 56 theme mortality 278:286 arg1 cause 238:242 a major cause 230:242 a major cause of serious neonatal morbidity and mortality 230:286 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 1 56 theme mortality 278:286 arg1 echovirus 208:216 example echovirus 11 200:219 example echovirus 11 (E11) 200:225 Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. 36560629 6 57 from complexes 894:902 arg1 patterns 861:868 its binding patterns 849:868 its binding patterns from reported DAF/virus complexes 849:902 DAF is a receptor for at least 20 enteroviruses and we classify its binding patterns from reported DAF/virus complexes into two distinct positions and orientations, named as E6 and E11 poses. 36560629 5 58 theme N-linked 721:728 arg1 glycan 730:735 the N-linked glycan 717:735 the N-linked glycan (residue 95 of DAF) 717:755 We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. 35831275 4 0 theme asymmetric 654:663 arg1 lobes 665:669 two asymmetric lobes 650:669 two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe 650:775 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 6 1 from differences 1006:1016 arg1 sequence 1025:1032 PrP sequence 1021:1032 PrP sequence 1021:1032 However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains. 35831275 3 2 theme same 488:491 arg1 protofilaments 493:506 the same protofilaments 484:506 the same protofilaments 484:506 We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. 35831275 4 3 theme PrP 562:564 arg1 monomer 566:572 a single PrP monomer 553:572 a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe 553:775 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 2 4 from preparations 304:315 arg1 present 265:271 present 265:271 present 265:271 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 1 5 theme misfolded 146:154 arg1 protein 175:181 misfolded host-encoded prion protein 146:181 misfolded host-encoded prion protein (PrP) 146:187 Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). 35831275 1 5 theme misfolded 146:154 arg1 PrP 184:186 PrP 184:186 PrP 184:186 Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). 35831275 4 6 theme single 555:560 arg1 monomer 566:572 a single PrP monomer 553:572 a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe 553:775 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 6 7 theme strains 1097:1103 arg1 features 1066:1073 distinguishing features 1051:1073 distinguishing features of the distinct prion strains 1051:1103 However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains. 35831275 4 8 with monomer 566:572 arg1 core 591:594 the ordered core 579:594 the ordered core 579:594 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 2 9 theme present 265:271 arg1 fibrils 257:263 PrP fibrils 253:263 PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 253:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 4 10 theme glycosylphosphatidylinositol 705:732 arg1 anchor 734:739 the glycosylphosphatidylinositol anchor 701:739 the glycosylphosphatidylinositol anchor 701:739 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 2 11 attach isolated 317:324 arg1 brains 335:340 the brains 331:340 the brains of RML prion-infected mice 331:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 2 11 attach isolated 317:324 arg2 preparations 304:315 highly infectious prion rod preparations 276:315 highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 276:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 4 12 link N-linked 680:687 arg1 glycans 689:695 the N-linked glycans 676:695 the N-linked glycans 676:695 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 2 13 theme fibrils 257:263 arg1 structure 240:248 a near-atomic resolution cryo-EM structure 207:248 a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 207:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 5 14 theme prion 917:921 arg1 strain 923:928 the 263K prion strain 908:928 the 263K prion strain 908:928 The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. 35831275 4 15 with lobes 665:669 arg1 anchor 734:739 the glycosylphosphatidylinositol anchor 701:739 the glycosylphosphatidylinositol anchor 701:739 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 4 15 with lobes 665:669 arg1 glycans 689:695 the N-linked glycans 676:695 the N-linked glycans 676:695 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 4 16 theme PrP 607:609 arg1 residues 611:618 PrP residues 94-225 607:625 PrP residues 94-225 607:625 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 1 17 theme Mammalian 54:62 arg1 prions 64:69 Mammalian prions 54:69 Mammalian prions 54:69 Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). 35831275 2 18 theme mice 364:367 arg1 brains 335:340 the brains 331:340 the brains of RML prion-infected mice 331:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 1 19 theme host-encoded 156:167 arg1 protein 175:181 misfolded host-encoded prion protein 146:181 misfolded host-encoded prion protein (PrP) 146:187 Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). 35831275 1 19 theme host-encoded 156:167 arg1 PrP 184:186 PrP 184:186 PrP 184:186 Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). 35831275 4 20 theme C-terminal 761:770 arg1 lobe 772:775 the C-terminal lobe 757:775 the C-terminal lobe 757:775 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 6 21 theme prion 1091:1095 arg1 strains 1097:1103 the distinct prion strains 1078:1103 the distinct prion strains 1078:1103 However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains. 35831275 1 22 theme prion 169:173 arg1 protein 175:181 misfolded host-encoded prion protein 146:181 misfolded host-encoded prion protein (PrP) 146:187 Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). 35831275 1 22 theme prion 169:173 arg1 PrP 184:186 PrP 184:186 PrP 184:186 Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). 35831275 0 23 theme cryo-EM 6:12 arg1 structure 14:22 cryo-EM structure 6:22 cryo-EM structure of ex vivo RML prion fibrils 6:51 2.7 Å cryo-EM structure of ex vivo RML prion fibrils. 35831275 6 24 theme distinct 1082:1089 arg1 strains 1097:1103 the distinct prion strains 1078:1103 the distinct prion strains 1078:1103 However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains. 35831275 2 25 theme prion 294:298 arg1 preparations 304:315 highly infectious prion rod preparations 276:315 highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 276:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 1 26 theme protein 175:181 arg1 assemblies 132:141 multichain assemblies 121:141 multichain assemblies of misfolded host-encoded prion protein (PrP) 121:187 Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). 35831275 6 27 theme conformational 957:970 arg1 variations 972:981 marked conformational variations 950:981 marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains 950:1103 However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains. 35831275 2 28 theme infectious 283:292 arg1 preparations 304:315 highly infectious prion rod preparations 276:315 highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 276:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 2 29 theme prion-infected 349:362 arg1 mice 364:367 RML prion-infected mice 345:367 RML prion-infected mice 345:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 6 30 theme marked 950:955 arg1 variations 972:981 marked conformational variations 950:981 marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains 950:1103 However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains. 35831275 5 31 theme hamsters 885:892 arg1 brain 876:880 the brain 872:880 the brain of hamsters infected with the 263K prion strain 872:928 The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. 35831275 1 32 theme distinct 84:91 arg1 strains 93:99 distinct strains 84:99 distinct strains 84:99 Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). 35831275 6 33 theme distinguishing 1051:1064 arg1 features 1066:1073 distinguishing features 1051:1073 distinguishing features of the distinct prion strains 1051:1103 However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains. 35831275 2 34 theme PrP 253:255 arg1 fibrils 257:263 PrP fibrils 253:263 PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 253:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 5 35 attach isolated 858:865 arg1 brain 876:880 the brain 872:880 the brain of hamsters infected with the 263K prion strain 872:928 The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. 35831275 5 35 attach isolated 858:865 arg2 fibrils 850:856 recently reported PrP fibrils 828:856 recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain 828:928 The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. 35831275 3 36 theme protofilaments 493:506 arg1 pairs 475:479 twisted pairs 467:479 twisted pairs of the same protofilaments 467:506 We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. 35831275 2 37 theme RML 345:347 arg1 mice 364:367 RML prion-infected mice 345:367 RML prion-infected mice 345:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 3 38 theme prion 384:388 arg1 rods 390:393 prion rods 384:393 prion rods 384:393 We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. 35831275 3 39 theme single-protofilament 404:423 arg1 fibrils 441:447 single-protofilament helical amyloid fibrils 404:447 single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments 404:506 We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. 35831275 5 40 theme reported 837:844 arg1 fibrils 850:856 recently reported PrP fibrils 828:856 recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain 828:928 The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. 35831275 0 41 theme ex 27:28 arg1 fibrils 45:51 ex vivo RML prion fibrils 27:51 ex vivo RML prion fibrils 27:51 2.7 Å cryo-EM structure of ex vivo RML prion fibrils. 35831275 5 42 theme PrP 846:848 arg1 fibrils 850:856 recently reported PrP fibrils 828:856 recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain 828:928 The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. 35831275 0 43 theme prion 39:43 arg1 fibrils 45:51 ex vivo RML prion fibrils 27:51 ex vivo RML prion fibrils 27:51 2.7 Å cryo-EM structure of ex vivo RML prion fibrils. 35831275 2 44 attach present 265:271 arg1 preparations 304:315 highly infectious prion rod preparations 276:315 highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 276:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 2 44 attach present 265:271 arg2 fibrils 257:263 PrP fibrils 253:263 PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 253:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 3 45 theme helical 425:431 arg1 fibrils 441:447 single-protofilament helical amyloid fibrils 404:447 single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments 404:506 We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. 35831275 4 46 dep residues 611:618 arg1 94-225 620:625 94-225 620:625 94-225 620:625 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 4 47 theme N-linked 680:687 arg1 glycans 689:695 the N-linked glycans 676:695 the N-linked glycans 676:695 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 0 48 theme RML 35:37 arg1 fibrils 45:51 ex vivo RML prion fibrils 27:51 ex vivo RML prion fibrils 27:51 2.7 Å cryo-EM structure of ex vivo RML prion fibrils. 35831275 4 49 theme protofilament 526:538 arg1 rung 514:517 Each rung 509:517 Each rung of the protofilament 509:538 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 0 50 dep ex 27:28 arg1 vivo 30:33 vivo 30:33 vivo 30:33 2.7 Å cryo-EM structure of ex vivo RML prion fibrils. 35831275 5 51 theme overall 782:788 arg1 comparable 806:815 comparable 806:815 comparable 806:815 The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. 35831275 5 51 theme overall 782:788 arg1 architecture 790:801 The overall architecture 778:801 The overall architecture 778:801 The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. 35831275 3 52 theme twisted 467:473 arg1 pairs 475:479 twisted pairs 467:479 twisted pairs of the same protofilaments 467:506 We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. 35831275 4 53 theme ordered 583:589 arg1 core 591:594 the ordered core 579:594 the ordered core 579:594 Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. 35831275 2 54 theme cryo-EM 232:238 arg1 structure 240:248 a near-atomic resolution cryo-EM structure 207:248 a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 207:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 2 55 theme rod 300:302 arg1 preparations 304:315 highly infectious prion rod preparations 276:315 highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 276:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 2 56 from present 265:271 arg1 preparations 304:315 highly infectious prion rod preparations 276:315 highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 276:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 5 57 theme 263K 912:915 arg1 strain 923:928 the 263K prion strain 908:928 the 263K prion strain 908:928 The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. 35831275 2 58 theme resolution 221:230 arg1 structure 240:248 a near-atomic resolution cryo-EM structure 207:248 a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 207:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 1 59 theme multichain 121:130 arg1 assemblies 132:141 multichain assemblies 121:141 multichain assemblies of misfolded host-encoded prion protein (PrP) 121:187 Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). 35831275 3 60 theme amyloid 433:439 arg1 fibrils 441:447 single-protofilament helical amyloid fibrils 404:447 single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments 404:506 We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. 35831275 0 61 theme fibrils 45:51 arg1 structure 14:22 cryo-EM structure 6:22 cryo-EM structure of ex vivo RML prion fibrils 6:51 2.7 Å cryo-EM structure of ex vivo RML prion fibrils. 35831275 2 62 theme near-atomic 209:219 arg1 structure 240:248 a near-atomic resolution cryo-EM structure 207:248 a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice 207:367 Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. 35831275 6 63 theme PrP 1021:1023 arg1 sequence 1025:1032 PrP sequence 1021:1032 PrP sequence 1021:1032 However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains. 34990750 14 0 theme envelope 2611:2618 arg1 proteins 2620:2627 the original envelope proteins 2598:2627 the original envelope proteins 2598:2627 HCV variants with modified envelope proteins exhibited similar immunogenicity as the virus with the original envelope proteins. 34990750 11 1 theme neutralizing 2008:2019 arg1 antibodies 2021:2030 neutralizing antibodies 2008:2030 neutralizing antibodies 2008:2030 CONCLUSION Using an adjuvant suitable for human use, we developed inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies. 34990750 4 2 theme MF-59 607:611 arg1 AddaVax 622:628 MF-59 analogue AddaVax 607:628 MF-59 analogue AddaVax 607:628 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 13 3 theme epidemiological 2474:2488 arg1 importance 2490:2499 recognized epidemiological importance 2463:2499 recognized epidemiological importance 2463:2499 We developed inactivated whole HCV vaccine candidates using adjuvants licensed for human use, which, following immunization of mice, induced antibodies that efficiently neutralized all HCV genotypes with recognized epidemiological importance. 34990750 14 4 with variants 2506:2513 arg1 proteins 2538:2545 modified envelope proteins 2520:2545 modified envelope proteins 2520:2545 HCV variants with modified envelope proteins exhibited similar immunogenicity as the virus with the original envelope proteins. 34990750 11 5 theme pre-clinical 2072:2083 arg1 studies 2085:2091 further pre-clinical studies 2064:2091 further pre-clinical studies 2064:2091 CONCLUSION Using an adjuvant suitable for human use, we developed inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies. 34990750 14 6 theme HCV 2502:2504 arg1 variants 2506:2513 HCV variants 2502:2513 HCV variants with modified envelope proteins 2502:2545 HCV variants with modified envelope proteins exhibited similar immunogenicity as the virus with the original envelope proteins. 34990750 10 7 theme epitope 1835:1841 arg1 exposure 1843:1850 increased neutralization epitope exposure 1810:1850 increased neutralization epitope exposure 1810:1850 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 6 8 theme HVR1 1154:1157 arg1 deletion 1142:1149 deletion 1142:1149 deletion of HVR1 1142:1157 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 2 9 theme HCV 271:273 arg1 candidates 283:292 whole virus inactivated HCV vaccine candidates 247:292 whole virus inactivated HCV vaccine candidates employing a licensed adjuvant 247:322 We developed whole virus inactivated HCV vaccine candidates employing a licensed adjuvant. 34990750 14 10 theme similar 2557:2563 arg1 immunogenicity 2565:2578 similar immunogenicity 2557:2578 similar immunogenicity 2557:2578 HCV variants with modified envelope proteins exhibited similar immunogenicity as the virus with the original envelope proteins. 34990750 14 10 theme similar 2557:2563 arg1 virus 2587:2591 the virus 2583:2591 the virus with the original envelope proteins 2583:2627 HCV variants with modified envelope proteins exhibited similar immunogenicity as the virus with the original envelope proteins. 34990750 6 11 theme E2 1081:1082 arg1 sequence 1084:1091 the original E2 sequence 1068:1091 the original E2 sequence determined in vivo 1068:1110 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 13 12 theme HCV 2444:2446 arg1 genotypes 2448:2456 all HCV genotypes 2440:2456 all HCV genotypes with recognized epidemiological importance 2440:2499 We developed inactivated whole HCV vaccine candidates using adjuvants licensed for human use, which, following immunization of mice, induced antibodies that efficiently neutralized all HCV genotypes with recognized epidemiological importance. 34990750 11 13 theme whole 1958:1962 arg1 candidates 1976:1985 inactivated whole HCV vaccine candidates 1946:1985 inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies 1946:2091 CONCLUSION Using an adjuvant suitable for human use, we developed inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies. 34990750 11 14 theme HCV 1964:1966 arg1 candidates 1976:1985 inactivated whole HCV vaccine candidates 1946:1985 inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies 1946:2091 CONCLUSION Using an adjuvant suitable for human use, we developed inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies. 34990750 8 15 theme RESULTS 1319:1325 arg1 HCV5aHi 1337:1343 RESULTS Processed HCV5aHi 1319:1343 RESULTS Processed HCV5aHi formulated with AddaVax 1319:1367 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 5 16 theme BALB/c 728:733 arg1 mice 735:738 immunized BALB/c mice 718:738 immunized BALB/c mice 718:738 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 4 17 dep adjuvant 597:604 arg1 AddaVax 622:628 MF-59 analogue AddaVax 607:628 MF-59 analogue AddaVax 607:628 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 4 17 dep adjuvant 597:604 arg1 hydroxide 643:651 aluminium hydroxide 633:651 aluminium hydroxide 633:651 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 5 18 dep investigated 658:669 arg1 ELISA 849:853 ELISA 849:853 ELISA 849:853 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 1 19 theme public 212:217 arg1 HCV 196:198 HCV 196:198 HCV 196:198 BACKGROUND & AIMS A prophylactic vaccine is required to eliminate HCV as a global public health threat. 34990750 1 19 theme public 212:217 arg1 threat 226:231 a global public health threat 203:231 a global public health threat 203:231 BACKGROUND & AIMS A prophylactic vaccine is required to eliminate HCV as a global public health threat. 34990750 6 20 theme SA13 917:920 arg1 proteins 931:938 strain SA13 envelope proteins 910:938 strain SA13 envelope proteins 910:938 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 9 21 theme aluminium 1629:1637 arg1 hydroxide 1639:1647 aluminium hydroxide 1629:1647 aluminium hydroxide 1629:1647 Vaccination with aluminium hydroxide was less immunogenic. 34990750 4 22 theme Whole 473:477 arg1 antigen 493:499 METHODS Whole virus vaccine antigen 465:499 METHODS Whole virus vaccine antigen 465:499 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 1 23 theme BACKGROUND 130:139 arg1 & 141:141 BACKGROUND & 130:141 BACKGROUND & 130:141 BACKGROUND & AIMS A prophylactic vaccine is required to eliminate HCV as a global public health threat. 34990750 6 24 dep HCV5aHi 1122:1128 arg1 iii 1117:1119 iii 1117:1119 iii 1117:1119 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 13 25 theme mice 2386:2389 arg1 immunization 2370:2381 immunization 2370:2381 immunization of mice 2370:2389 We developed inactivated whole HCV vaccine candidates using adjuvants licensed for human use, which, following immunization of mice, induced antibodies that efficiently neutralized all HCV genotypes with recognized epidemiological importance. 34990750 2 26 theme virus 253:257 arg1 candidates 283:292 whole virus inactivated HCV vaccine candidates 247:292 whole virus inactivated HCV vaccine candidates employing a licensed adjuvant 247:322 We developed whole virus inactivated HCV vaccine candidates employing a licensed adjuvant. 34990750 14 27 theme envelope 2529:2536 arg1 proteins 2538:2545 modified envelope proteins 2520:2545 modified envelope proteins 2520:2545 HCV variants with modified envelope proteins exhibited similar immunogenicity as the virus with the original envelope proteins. 34990750 6 28 dep HCV5aHi 897:903 arg1 i 894:894 i 894:894 i 894:894 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 8 29 dep 192 μg/ml 1553:1561 arg1 mean 1564:1567 mean 1564:1567 mean of 36 μg/ml against the homologous virus 1564:1608 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 0 30 theme hepatitis 18:26 arg1 virus 30:34 whole hepatitis C virus 12:34 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant 0:72 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant elicits cross-genotype neutralizing antibodies in mice. 34990750 1 31 theme prophylactic 150:161 arg1 vaccine 163:169 A prophylactic vaccine 148:169 A prophylactic vaccine 148:169 BACKGROUND & AIMS A prophylactic vaccine is required to eliminate HCV as a global public health threat. 34990750 8 32 theme 192 μg/ml 1553:1561 arg1 concentrations 1520:1533 half maximal inhibitory concentrations 1496:1533 half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus) 1496:1609 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 12 33 theme new 2193:2195 arg1 infections 2197:2206 2 million new infections 2183:2206 2 million new infections 2183:2206 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 6 34 from E2 994:995 arg1 modification 944:955 modification 944:955 modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1 944:1157 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 6 34 from E2 994:995 arg1 proteins 931:938 strain SA13 envelope proteins 910:938 strain SA13 envelope proteins 910:938 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 6 35 theme glycosylation 972:984 arg1 site 986:989 an O-linked glycosylation site 960:989 an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1 960:1157 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 4 36 theme hepatoma 524:531 arg1 cells 533:537 Huh7.5 hepatoma cells 517:537 Huh7.5 hepatoma cells 517:537 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 3 37 dep modifications 386:398 arg1 increase 404:411 increase 404:411 to increase neutralization epitope exposure 401:443 Further, we investigated the effects of HCV envelope protein modifications (to increase neutralization epitope exposure) on immunogenicity. 34990750 0 38 theme neutralizing 97:108 arg1 antibodies 110:119 cross-genotype neutralizing antibodies 82:119 cross-genotype neutralizing antibodies 82:119 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant elicits cross-genotype neutralizing antibodies in mice. 34990750 4 39 theme vaccine 485:491 arg1 antigen 493:499 METHODS Whole virus vaccine antigen 465:499 METHODS Whole virus vaccine antigen 465:499 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 5 40 theme genotype 754:761 arg1 HCV 767:769 genotype 1-6 HCV 754:769 genotype 1-6 HCV (by virus neutralization assays) 754:802 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 5 41 dep capacity 675:682 arg1 neutralize 743:752 neutralize 743:752 to neutralize genotype 1-6 HCV (by virus neutralization assays) 740:802 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 5 41 dep capacity 675:682 arg1 bind 811:814 bind 811:814 to bind homologous envelope proteins 808:843 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 6 42 from site 986:989 arg1 E2 994:995 E2 994:995 E2 (T385P) 994:1003 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 6 42 from site 986:989 arg1 T385P 998:1002 T385P 998:1002 T385P 998:1002 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 6 42 from site 986:989 arg1 T385 1019:1022 T385 1019:1022 T385 1019:1022 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 0 43 theme Inactivated 0:10 arg1 vaccine 36:42 Inactivated whole hepatitis C virus vaccine 0:42 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant 0:72 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant elicits cross-genotype neutralizing antibodies in mice. 34990750 7 44 theme human 1219:1223 arg1 antibodies 1282:1291 human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies 1219:1291 human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies 1219:1291 For these viruses, epitope exposure was investigated using human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies in neutralization assays. 34990750 3 45 theme envelope 369:376 arg1 modifications 386:398 HCV envelope protein modifications 365:398 HCV envelope protein modifications (to increase neutralization epitope exposure) 365:444 Further, we investigated the effects of HCV envelope protein modifications (to increase neutralization epitope exposure) on immunogenicity. 34990750 4 46 theme multistep 558:566 arg1 protocol 568:575 a multistep protocol 556:575 a multistep protocol 556:575 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 6 47 dep T385 1019:1022 arg1 ii 1007:1008 ii 1007:1008 ii 1007:1008 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 9 48 with Vaccination 1612:1622 arg1 hydroxide 1639:1647 aluminium hydroxide 1629:1647 aluminium hydroxide 1629:1647 Vaccination with aluminium hydroxide was less immunogenic. 34990750 5 49 theme homologous 816:825 arg1 proteins 836:843 homologous envelope proteins 816:843 homologous envelope proteins 816:843 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 13 50 theme human 2342:2346 arg1 use 2348:2350 human use 2342:2350 human use 2342:2350 We developed inactivated whole HCV vaccine candidates using adjuvants licensed for human use, which, following immunization of mice, induced antibodies that efficiently neutralized all HCV genotypes with recognized epidemiological importance. 34990750 3 51 theme neutralization 413:426 arg1 exposure 436:443 neutralization epitope exposure 413:443 neutralization epitope exposure 413:443 Further, we investigated the effects of HCV envelope protein modifications (to increase neutralization epitope exposure) on immunogenicity. 34990750 8 52 theme genotype 1473:1480 arg1 HCV 1486:1488 cultured genotype 1-6 HCV 1464:1488 cultured genotype 1-6 HCV 1464:1488 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 5 53 theme neutralization 781:794 arg1 assays 796:801 virus neutralization assays 775:801 virus neutralization assays 775:801 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 0 54 theme virus 30:34 arg1 vaccine 36:42 Inactivated whole hepatitis C virus vaccine 0:42 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant 0:72 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant elicits cross-genotype neutralizing antibodies in mice. 34990750 13 55 theme vaccine 2294:2300 arg1 candidates 2302:2311 inactivated whole HCV vaccine candidates 2272:2311 inactivated whole HCV vaccine candidates 2272:2311 We developed inactivated whole HCV vaccine candidates using adjuvants licensed for human use, which, following immunization of mice, induced antibodies that efficiently neutralized all HCV genotypes with recognized epidemiological importance. 34990750 10 56 theme modified 1743:1750 arg1 site 1766:1769 a modified glycosylation site 1741:1769 a modified glycosylation site 1741:1769 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 12 57 theme C 2134:2134 arg1 HCV 2143:2145 HCV 2143:2145 HCV 2143:2145 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 12 57 theme C 2134:2134 arg1 virus 2136:2140 hepatitis C virus 2124:2140 hepatitis C virus (HCV) 2124:2146 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 12 58 dep infections 2197:2206 arg1 the 2169:2171 the 2169:2171 the 2169:2171 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 12 59 theme LAY 2094:2096 arg1 vaccine 2108:2114 LAY SUMMARY A vaccine 2094:2114 LAY SUMMARY A vaccine against hepatitis C virus (HCV) 2094:2146 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 1 60 theme health 219:224 arg1 HCV 196:198 HCV 196:198 HCV 196:198 BACKGROUND & AIMS A prophylactic vaccine is required to eliminate HCV as a global public health threat. 34990750 1 60 theme health 219:224 arg1 threat 226:231 a global public health threat 203:231 a global public health threat 203:231 BACKGROUND & AIMS A prophylactic vaccine is required to eliminate HCV as a global public health threat. 34990750 11 61 theme human 1922:1926 arg1 use 1928:1930 human use 1922:1930 human use 1922:1930 CONCLUSION Using an adjuvant suitable for human use, we developed inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies. 34990750 6 62 theme T385P 1043:1047 arg1 reversion 1030:1038 reversion 1030:1038 reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1 1030:1157 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 8 63 theme maximal 1501:1507 arg1 concentrations 1520:1533 half maximal inhibitory concentrations 1496:1533 half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus) 1496:1609 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 12 64 theme A 2106:2106 arg1 vaccine 2108:2114 LAY SUMMARY A vaccine 2094:2114 LAY SUMMARY A vaccine against hepatitis C virus (HCV) 2094:2146 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 13 65 theme whole 2284:2288 arg1 candidates 2302:2311 inactivated whole HCV vaccine candidates 2272:2311 inactivated whole HCV vaccine candidates 2272:2311 We developed inactivated whole HCV vaccine candidates using adjuvants licensed for human use, which, following immunization of mice, induced antibodies that efficiently neutralized all HCV genotypes with recognized epidemiological importance. 34990750 13 66 with genotypes 2448:2456 arg1 importance 2490:2499 recognized epidemiological importance 2463:2499 recognized epidemiological importance 2463:2499 We developed inactivated whole HCV vaccine candidates using adjuvants licensed for human use, which, following immunization of mice, induced antibodies that efficiently neutralized all HCV genotypes with recognized epidemiological importance. 34990750 14 67 theme original 2602:2609 arg1 proteins 2620:2627 the original envelope proteins 2598:2627 the original envelope proteins 2598:2627 HCV variants with modified envelope proteins exhibited similar immunogenicity as the virus with the original envelope proteins. 34990750 13 68 theme recognized 2463:2472 arg1 importance 2490:2499 recognized epidemiological importance 2463:2499 recognized epidemiological importance 2463:2499 We developed inactivated whole HCV vaccine candidates using adjuvants licensed for human use, which, following immunization of mice, induced antibodies that efficiently neutralized all HCV genotypes with recognized epidemiological importance. 34990750 8 69 theme homologous 1593:1602 arg1 virus 1604:1608 the homologous virus 1589:1608 the homologous virus 1589:1608 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 11 70 theme inactivated 1946:1956 arg1 candidates 1976:1985 inactivated whole HCV vaccine candidates 1946:1985 inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies 1946:2091 CONCLUSION Using an adjuvant suitable for human use, we developed inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies. 34990750 14 71 with virus 2587:2591 arg1 proteins 2620:2627 the original envelope proteins 2598:2627 the original envelope proteins 2598:2627 HCV variants with modified envelope proteins exhibited similar immunogenicity as the virus with the original envelope proteins. 34990750 2 72 theme vaccine 275:281 arg1 candidates 283:292 whole virus inactivated HCV vaccine candidates 247:292 whole virus inactivated HCV vaccine candidates employing a licensed adjuvant 247:322 We developed whole virus inactivated HCV vaccine candidates employing a licensed adjuvant. 34990750 7 73 theme neutralization 1296:1309 arg1 assays 1311:1316 neutralization assays 1296:1316 neutralization assays 1296:1316 For these viruses, epitope exposure was investigated using human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies in neutralization assays. 34990750 10 74 theme neutralization 1820:1833 arg1 exposure 1843:1850 increased neutralization epitope exposure 1810:1850 increased neutralization epitope exposure 1810:1850 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 6 75 link O-linked 963:970 arg1 site 986:989 an O-linked glycosylation site 960:989 an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1 960:1157 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 11 76 theme further 2064:2070 arg1 studies 2085:2091 further pre-clinical studies 2064:2091 further pre-clinical studies 2064:2091 CONCLUSION Using an adjuvant suitable for human use, we developed inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies. 34990750 6 77 theme original 1072:1079 arg1 sequence 1084:1091 the original E2 sequence 1068:1091 the original E2 sequence determined in vivo 1068:1110 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 5 78 theme envelope 827:834 arg1 proteins 836:843 homologous envelope proteins 816:843 homologous envelope proteins 816:843 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 4 79 theme METHODS 465:471 arg1 antigen 493:499 METHODS Whole virus vaccine antigen 465:499 METHODS Whole virus vaccine antigen 465:499 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 10 80 theme similar 1856:1862 arg1 immunogenicity 1864:1877 similar immunogenicity 1856:1877 similar immunogenicity 1856:1877 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 5 81 theme immunized 718:726 arg1 mice 735:738 immunized BALB/c mice 718:738 immunized BALB/c mice 718:738 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 3 82 from effects 354:360 arg1 immunogenicity 449:462 immunogenicity 449:462 immunogenicity 449:462 Further, we investigated the effects of HCV envelope protein modifications (to increase neutralization epitope exposure) on immunogenicity. 34990750 1 83 theme global 205:210 arg1 HCV 196:198 HCV 196:198 HCV 196:198 BACKGROUND & AIMS A prophylactic vaccine is required to eliminate HCV as a global public health threat. 34990750 1 83 theme global 205:210 arg1 threat 226:231 a global public health threat 203:231 a global public health threat 203:231 BACKGROUND & AIMS A prophylactic vaccine is required to eliminate HCV as a global public health threat. 34990750 6 84 theme envelope 922:929 arg1 proteins 931:938 strain SA13 envelope proteins 910:938 strain SA13 envelope proteins 910:938 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 11 85 theme vaccine 1968:1974 arg1 candidates 1976:1985 inactivated whole HCV vaccine candidates 1946:1985 inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies 1946:2091 CONCLUSION Using an adjuvant suitable for human use, we developed inactivated whole HCV vaccine candidates that induced broadly neutralizing antibodies, which warrant investigation in further pre-clinical studies. 34990750 4 86 theme virus 479:483 arg1 antigen 493:499 METHODS Whole virus vaccine antigen 465:499 METHODS Whole virus vaccine antigen 465:499 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 5 87 theme IgG 687:689 arg1 capacity 675:682 the capacity 671:682 the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins 671:843 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 10 88 theme original 1706:1713 arg1 sequence 1718:1725 the original E2 sequence 1702:1725 the original E2 sequence 1702:1725 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 6 89 theme strain 910:915 arg1 proteins 931:938 strain SA13 envelope proteins 910:938 strain SA13 envelope proteins 910:938 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 7 90 theme polyclonal 1256:1265 arg1 antibodies 1282:1291 human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies 1219:1291 human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies 1219:1291 For these viruses, epitope exposure was investigated using human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies in neutralization assays. 34990750 2 91 theme inactivated 259:269 arg1 candidates 283:292 whole virus inactivated HCV vaccine candidates 247:292 whole virus inactivated HCV vaccine candidates employing a licensed adjuvant 247:322 We developed whole virus inactivated HCV vaccine candidates employing a licensed adjuvant. 34990750 5 92 theme 1-6 763:765 arg1 HCV 767:769 genotype 1-6 HCV 754:769 genotype 1-6 HCV (by virus neutralization assays) 754:802 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 2 93 theme whole 247:251 arg1 candidates 283:292 whole virus inactivated HCV vaccine candidates 247:292 whole virus inactivated HCV vaccine candidates employing a licensed adjuvant 247:322 We developed whole virus inactivated HCV vaccine candidates employing a licensed adjuvant. 34990750 14 94 theme modified 2520:2527 arg1 proteins 2538:2545 modified envelope proteins 2520:2545 modified envelope proteins 2520:2545 HCV variants with modified envelope proteins exhibited similar immunogenicity as the virus with the original envelope proteins. 34990750 4 95 theme Huh7.5 517:522 arg1 cells 533:537 Huh7.5 hepatoma cells 517:537 Huh7.5 hepatoma cells 517:537 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 0 96 theme cross-genotype 82:95 arg1 antibodies 110:119 cross-genotype neutralizing antibodies 82:119 cross-genotype neutralizing antibodies 82:119 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant elicits cross-genotype neutralizing antibodies in mice. 34990750 6 97 theme site 986:989 arg1 modification 944:955 modification 944:955 modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1 944:1157 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 6 97 theme site 986:989 arg1 proteins 931:938 strain SA13 envelope proteins 910:938 strain SA13 envelope proteins 910:938 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 8 98 theme homologous 1411:1420 arg1 proteins 1431:1438 homologous envelope proteins 1411:1438 homologous envelope proteins 1411:1438 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 8 99 theme Processed 1327:1335 arg1 HCV5aHi 1337:1343 RESULTS Processed HCV5aHi 1319:1343 RESULTS Processed HCV5aHi formulated with AddaVax 1319:1367 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 5 100 theme mice 735:738 arg1 serum 709:713 the serum 705:713 the serum of immunized BALB/c mice 705:738 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 6 101 theme O-linked 963:970 arg1 site 986:989 an O-linked glycosylation site 960:989 an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1 960:1157 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 3 102 theme HCV 365:367 arg1 modifications 386:398 HCV envelope protein modifications 365:398 HCV envelope protein modifications (to increase neutralization epitope exposure) 365:444 Further, we investigated the effects of HCV envelope protein modifications (to increase neutralization epitope exposure) on immunogenicity. 34990750 12 103 theme estimated 2173:2181 arg1 infections 2197:2206 2 million new infections 2183:2206 2 million new infections 2183:2206 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 7 104 theme monoclonal 1225:1234 arg1 antibodies 1282:1291 human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies 1219:1291 human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies 1219:1291 For these viruses, epitope exposure was investigated using human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies in neutralization assays. 34990750 12 105 theme million 2185:2191 arg1 infections 2197:2206 2 million new infections 2183:2206 2 million new infections 2183:2206 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 4 106 theme analogue 613:620 arg1 AddaVax 622:628 MF-59 analogue AddaVax 607:628 MF-59 analogue AddaVax 607:628 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 0 107 theme whole 12:16 arg1 virus 30:34 whole hepatitis C virus 12:34 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant 0:72 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant elicits cross-genotype neutralizing antibodies in mice. 34990750 8 108 theme envelope 1422:1429 arg1 proteins 1431:1438 homologous envelope proteins 1411:1438 homologous envelope proteins 1411:1438 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 8 109 theme cultured 1464:1471 arg1 HCV 1486:1488 cultured genotype 1-6 HCV 1464:1488 cultured genotype 1-6 HCV 1464:1488 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 12 110 theme each 2248:2251 arg1 year 2253:2256 this virus each year 2237:2256 this virus each year 2237:2256 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 12 111 theme virus 2242:2246 arg1 year 2253:2256 this virus each year 2237:2256 this virus each year 2237:2256 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 0 112 theme C 28:28 arg1 virus 30:34 whole hepatitis C virus 12:34 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant 0:72 Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant elicits cross-genotype neutralizing antibodies in mice. 34990750 3 113 theme protein 378:384 arg1 modifications 386:398 HCV envelope protein modifications 365:398 HCV envelope protein modifications (to increase neutralization epitope exposure) 365:444 Further, we investigated the effects of HCV envelope protein modifications (to increase neutralization epitope exposure) on immunogenicity. 34990750 6 114 from proteins 931:938 arg1 E2 994:995 E2 994:995 E2 (T385P) 994:1003 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 6 114 from proteins 931:938 arg1 T385P 998:1002 T385P 998:1002 T385P 998:1002 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 6 114 from proteins 931:938 arg1 T385 1019:1022 T385 1019:1022 T385 1019:1022 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 5 115 theme virus 775:779 arg1 assays 796:801 virus neutralization assays 775:801 virus neutralization assays 775:801 We investigated the capacity of IgG purified from the serum of immunized BALB/c mice to neutralize genotype 1-6 HCV (by virus neutralization assays) and to bind homologous envelope proteins (by ELISA). 34990750 13 116 theme HCV 2290:2292 arg1 candidates 2302:2311 inactivated whole HCV vaccine candidates 2272:2311 inactivated whole HCV vaccine candidates 2272:2311 We developed inactivated whole HCV vaccine candidates using adjuvants licensed for human use, which, following immunization of mice, induced antibodies that efficiently neutralized all HCV genotypes with recognized epidemiological importance. 34990750 7 117 theme epitope 1179:1185 arg1 exposure 1187:1194 epitope exposure 1179:1194 epitope exposure 1179:1194 For these viruses, epitope exposure was investigated using human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies in neutralization assays. 34990750 3 118 theme epitope 428:434 arg1 exposure 436:443 neutralization epitope exposure 413:443 neutralization epitope exposure 413:443 Further, we investigated the effects of HCV envelope protein modifications (to increase neutralization epitope exposure) on immunogenicity. 34990750 6 119 from modification 944:955 arg1 E2 994:995 E2 994:995 E2 (T385P) 994:1003 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 6 119 from modification 944:955 arg1 T385P 998:1002 T385P 998:1002 T385P 998:1002 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 6 119 from modification 944:955 arg1 T385 1019:1022 T385 1019:1022 T385 1019:1022 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 10 120 theme glycosylation 1752:1764 arg1 site 1766:1769 a modified glycosylation site 1741:1769 a modified glycosylation site 1741:1769 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 6 121 gly glycosylation 972:984 arg2 site 986:989 an O-linked glycosylation site 960:989 an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1 960:1157 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 10 122 with HCV5aHi 1728:1734 arg1 site 1766:1769 a modified glycosylation site 1741:1769 a modified glycosylation site 1741:1769 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 10 122 with HCV5aHi 1728:1734 arg1 ΔHVR1 1783:1787 ΔHVR1 1783:1787 ΔHVR1 1783:1787 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 10 122 with HCV5aHi 1728:1734 arg1 HCV5aHi 1775:1781 HCV5aHi 1775:1781 HCV5aHi(ΔHVR1) 1775:1788 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 7 123 dep monoclonal 1225:1234 arg1 AR4A 1246:1249 AR4A 1246:1249 AR4A 1246:1249 For these viruses, epitope exposure was investigated using human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies in neutralization assays. 34990750 7 123 dep monoclonal 1225:1234 arg1 AR3A 1237:1240 AR3A 1237:1240 AR3A 1237:1240 For these viruses, epitope exposure was investigated using human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies in neutralization assays. 34990750 7 123 dep monoclonal 1225:1234 arg1 H06 1277:1279 H06 1277:1279 H06 1277:1279 For these viruses, epitope exposure was investigated using human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies in neutralization assays. 34990750 7 123 dep monoclonal 1225:1234 arg1 C211 1268:1271 C211 1268:1271 C211 1268:1271 For these viruses, epitope exposure was investigated using human monoclonal (AR3A and AR4A) and polyclonal (C211 and H06) antibodies in neutralization assays. 34990750 12 124 theme hepatitis 2124:2132 arg1 HCV 2143:2145 HCV 2143:2145 HCV 2143:2145 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 12 124 theme hepatitis 2124:2132 arg1 virus 2136:2140 hepatitis C virus 2124:2140 hepatitis C virus (HCV) 2124:2146 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 10 125 theme E2 1715:1716 arg1 sequence 1718:1725 the original E2 sequence 1702:1725 the original E2 sequence 1702:1725 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 6 126 with HCV5aHi 897:903 arg1 modification 944:955 modification 944:955 modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1 944:1157 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 6 126 with HCV5aHi 897:903 arg1 proteins 931:938 strain SA13 envelope proteins 910:938 strain SA13 envelope proteins 910:938 Viruses used for immunizations were (i) HCV5aHi with strain SA13 envelope proteins and modification of an O-linked glycosylation site in E2 (T385P), (ii) HCV5aHi(T385) with reversion of T385P to T385, featuring the original E2 sequence determined in vivo and (iii) HCV5aHi(ΔHVR1) with deletion of HVR1. 34990750 8 127 theme inhibitory 1509:1518 arg1 concentrations 1520:1533 half maximal inhibitory concentrations 1496:1533 half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus) 1496:1609 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 8 128 theme 36 μg/ml 1572:1579 arg1 mean 1564:1567 mean 1564:1567 mean of 36 μg/ml against the homologous virus 1564:1608 RESULTS Processed HCV5aHi formulated with AddaVax induced antibodies that efficiently bound homologous envelope proteins and broadly neutralized cultured genotype 1-6 HCV, with half maximal inhibitory concentrations of between 14 and 192 μg/ml (mean of 36 μg/ml against the homologous virus). 34990750 10 129 gly glycosylation 1752:1764 arg2 site 1766:1769 a modified glycosylation site 1741:1769 a modified glycosylation site 1741:1769 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 13 130 theme inactivated 2272:2282 arg1 candidates 2302:2311 inactivated whole HCV vaccine candidates 2272:2311 inactivated whole HCV vaccine candidates 2272:2311 We developed inactivated whole HCV vaccine candidates using adjuvants licensed for human use, which, following immunization of mice, induced antibodies that efficiently neutralized all HCV genotypes with recognized epidemiological importance. 34990750 4 131 theme aluminium 633:641 arg1 hydroxide 643:651 aluminium hydroxide 633:651 aluminium hydroxide 633:651 METHODS Whole virus vaccine antigen was produced in Huh7.5 hepatoma cells, processed using a multistep protocol and formulated with adjuvant (MF-59 analogue AddaVax or aluminium hydroxide). 34990750 10 132 theme increased 1810:1818 arg1 exposure 1843:1850 increased neutralization epitope exposure 1810:1850 increased neutralization epitope exposure 1810:1850 Compared to HCV5aHi(T385) with the original E2 sequence, HCV5aHi with a modified glycosylation site and HCV5aHi(ΔHVR1) without HVR1 showed increased neutralization epitope exposure but similar immunogenicity. 34990750 12 133 theme SUMMARY 2098:2104 arg1 vaccine 2108:2114 LAY SUMMARY A vaccine 2094:2114 LAY SUMMARY A vaccine against hepatitis C virus (HCV) 2094:2146 LAY SUMMARY A vaccine against hepatitis C virus (HCV) is needed to prevent the estimated 2 million new infections and 400,000 deaths caused by this virus each year. 34990750 3 134 theme modifications 386:398 arg1 effects 354:360 the effects 350:360 the effects of HCV envelope protein modifications (to increase neutralization epitope exposure) on immunogenicity 350:462 Further, we investigated the effects of HCV envelope protein modifications (to increase neutralization epitope exposure) on immunogenicity. 34985906 0 0 theme Modifications 101:113 arg1 Mapping 56:62 Chemoproteomic Mapping 41:62 Chemoproteomic Mapping of Its Endogenous Post-translational Modifications 41:113 Bicyclic Picomolar OGA Inhibitors Enable Chemoproteomic Mapping of Its Endogenous Post-translational Modifications. 34985906 6 1 theme inhibitors 911:920 arg1 Structures 891:900 Structures 891:900 Structures of these inhibitors in complex with human OGA 891:946 Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. 34985906 10 2 dep inhibitors 1618:1627 arg1 the 1614:1616 the 1614:1616 the 1614:1616 Moreover, the inhibitors and structures described here lay out a blueprint that will enable the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes. 34985906 2 3 theme O-GlcNAc 353:360 arg1 presence 341:348 the presence 337:348 the presence of O-GlcNAc on hundreds of proteins within cells 337:397 Despite the presence of O-GlcNAc on hundreds of proteins within cells, only two enzymes regulate this modification. 34985906 7 4 theme endogenous 1177:1186 arg1 OGA 1188:1190 endogenous OGA 1177:1190 endogenous OGA 1177:1190 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 0 5 theme Post-translational 82:99 arg1 Modifications 101:113 Its Endogenous Post-translational Modifications 67:113 Its Endogenous Post-translational Modifications 67:113 Bicyclic Picomolar OGA Inhibitors Enable Chemoproteomic Mapping of Its Endogenous Post-translational Modifications. 34985906 7 6 theme high 1097:1100 arg1 probe 1126:1130 a high affinity chemoproteomic probe 1095:1130 a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications 1095:1272 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 10 7 theme chemical 1712:1719 arg1 probes 1721:1726 chemical probes 1712:1726 chemical probes 1712:1726 Moreover, the inhibitors and structures described here lay out a blueprint that will enable the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes. 34985906 7 8 theme OGA 1188:1190 arg1 mapping 1226:1232 targeted proteomic mapping 1207:1232 targeted proteomic mapping of its post-translational modifications 1207:1272 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 7 8 theme OGA 1188:1190 arg1 purification 1161:1172 simple one-step purification 1145:1172 simple one-step purification of endogenous OGA from brain 1145:1201 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 9 9 theme chemoproteomics 1440:1454 arg1 probes 1456:1461 chemoproteomics probes 1440:1461 chemoproteomics probes 1440:1461 We expect that these inhibitors and chemoproteomics probes will prove useful as fundamental tools to decipher the mechanisms by which OGA is regulated and directed to its diverse cellular substrates. 34985906 4 10 theme O-GlcNAc 732:739 arg1 pathway 741:747 the O-GlcNAc pathway 728:747 the O-GlcNAc pathway 728:747 Chemical tools to control OGA are emerging as essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway. 34985906 9 11 theme cellular 1583:1590 arg1 substrates 1592:1601 its diverse cellular substrates 1571:1601 its diverse cellular substrates 1571:1601 We expect that these inhibitors and chemoproteomics probes will prove useful as fundamental tools to decipher the mechanisms by which OGA is regulated and directed to its diverse cellular substrates. 34985906 6 12 theme exceptional 975:985 arg1 potency 987:993 their exceptional potency 969:993 their exceptional potency 969:993 Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. 34985906 4 13 theme cellular 706:713 arg1 functions 715:723 the biochemical and cellular functions 686:723 the biochemical and cellular functions of the O-GlcNAc pathway 686:747 Chemical tools to control OGA are emerging as essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway. 34985906 2 14 from presence 341:348 arg1 hundreds 365:372 hundreds 365:372 hundreds of proteins within cells 365:397 Despite the presence of O-GlcNAc on hundreds of proteins within cells, only two enzymes regulate this modification. 34985906 10 15 theme probes 1721:1726 arg1 creation 1700:1707 the creation 1696:1707 the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes 1696:1793 Moreover, the inhibitors and structures described here lay out a blueprint that will enable the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes. 34985906 6 16 from Structures 891:900 arg1 complex 925:931 complex 925:931 complex with human OGA 925:946 Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. 34985906 2 17 attach presence 341:348 arg2 O-GlcNAc 353:360 O-GlcNAc 353:360 O-GlcNAc 353:360 Despite the presence of O-GlcNAc on hundreds of proteins within cells, only two enzymes regulate this modification. 34985906 2 17 attach presence 341:348 arg1 hundreds 365:372 hundreds 365:372 hundreds of proteins within cells 365:397 Despite the presence of O-GlcNAc on hundreds of proteins within cells, only two enzymes regulate this modification. 34985906 4 18 theme Chemical 598:605 arg1 tools 607:611 Chemical tools 598:611 Chemical tools to control OGA 598:626 Chemical tools to control OGA are emerging as essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway. 34985906 3 19 theme glycoside 498:506 arg1 hydrolase 508:516 a dimeric glycoside hydrolase 488:516 a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated 488:595 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 3 19 theme glycoside 498:506 arg1 O-GlcNAcase 469:479 O-GlcNAcase 469:479 O-GlcNAcase (OGA) 469:485 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 1 20 theme nuclear 184:190 arg1 proteins 224:231 nuclear, cytoplasmic, and mitochondrial proteins 184:231 nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) 184:285 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 7 21 theme chemoproteomic 1111:1124 arg1 probe 1126:1130 a high affinity chemoproteomic probe 1095:1130 a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications 1095:1272 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 5 22 theme designed 778:785 arg1 inhibitors 809:818 rationally designed bicyclic thiazolidine inhibitors 767:818 rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA 767:888 Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. 34985906 1 23 link O-linked 238:245 arg1 O-GlcNAc 277:284 O-GlcNAc 277:284 O-GlcNAc 277:284 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 1 23 link O-linked 238:245 arg1 residues 267:274 O-linked N-acetylglucosamine residues 238:274 O-linked N-acetylglucosamine residues (O-GlcNAc) 238:285 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 4 24 theme pathway 741:747 arg1 functions 715:723 the biochemical and cellular functions 686:723 the biochemical and cellular functions of the O-GlcNAc pathway 686:747 Chemical tools to control OGA are emerging as essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway. 34985906 3 25 contain has 523:525 arg2 cleft 546:550 a deep active site cleft 527:550 a deep active site cleft in which diverse substrates are accommodated 527:595 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 3 25 contain has 523:525 arg1 hydrolase 508:516 a dimeric glycoside hydrolase 488:516 a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated 488:595 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 3 25 contain has 523:525 arg1 O-GlcNAcase 469:479 O-GlcNAcase 469:479 O-GlcNAcase (OGA) 469:485 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 0 26 theme Picomolar 9:17 arg1 Inhibitors 23:32 Bicyclic Picomolar OGA Inhibitors 0:32 Bicyclic Picomolar OGA Inhibitors 0:32 Bicyclic Picomolar OGA Inhibitors Enable Chemoproteomic Mapping of Its Endogenous Post-translational Modifications. 34985906 7 27 theme targeted 1207:1214 arg1 mapping 1226:1232 targeted proteomic mapping 1207:1232 targeted proteomic mapping of its post-translational modifications 1207:1272 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 3 28 theme active 534:539 arg1 cleft 546:550 a deep active site cleft 527:550 a deep active site cleft in which diverse substrates are accommodated 527:595 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 7 29 theme one-step 1152:1159 arg1 purification 1161:1172 simple one-step purification 1145:1172 simple one-step purification of endogenous OGA from brain 1145:1201 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 2 30 theme proteins 377:384 arg1 hundreds 365:372 hundreds 365:372 hundreds of proteins within cells 365:397 Despite the presence of O-GlcNAc on hundreds of proteins within cells, only two enzymes regulate this modification. 34985906 0 31 theme Bicyclic 0:7 arg1 Inhibitors 23:32 Bicyclic Picomolar OGA Inhibitors 0:32 Bicyclic Picomolar OGA Inhibitors 0:32 Bicyclic Picomolar OGA Inhibitors Enable Chemoproteomic Mapping of Its Endogenous Post-translational Modifications. 34985906 8 32 dep less-known 1348:1357 arg1 such 1360:1363 such 1360:1363 such 1360:1363 These data uncover a range of new modifications, including some that are less-known, such as O-ubiquitination and N-formylation. 34985906 1 33 from roles 129:133 arg1 disease 155:161 disease 155:161 disease 155:161 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 1 33 from roles 129:133 arg1 health 144:149 human health 138:149 human health 138:149 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 3 34 theme site 541:544 arg1 cleft 546:550 a deep active site cleft 527:550 a deep active site cleft in which diverse substrates are accommodated 527:595 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 6 35 theme active 1039:1044 arg1 cleft 1051:1055 the enzyme active site cleft 1028:1055 the enzyme active site cleft 1028:1055 Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. 34985906 5 36 theme thiazolidine 796:807 arg1 inhibitors 809:818 rationally designed bicyclic thiazolidine inhibitors 767:818 rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA 767:888 Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. 34985906 5 37 theme bicyclic 787:794 arg1 inhibitors 809:818 rationally designed bicyclic thiazolidine inhibitors 767:818 rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA 767:888 Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. 34985906 9 38 theme diverse 1575:1581 arg1 substrates 1592:1601 its diverse cellular substrates 1571:1601 its diverse cellular substrates 1571:1601 We expect that these inhibitors and chemoproteomics probes will prove useful as fundamental tools to decipher the mechanisms by which OGA is regulated and directed to its diverse cellular substrates. 34985906 1 39 theme cytoplasmic 193:203 arg1 proteins 224:231 nuclear, cytoplasmic, and mitochondrial proteins 184:231 nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) 184:285 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 0 40 theme OGA 19:21 arg1 Inhibitors 23:32 Bicyclic Picomolar OGA Inhibitors 0:32 Bicyclic Picomolar OGA Inhibitors 0:32 Bicyclic Picomolar OGA Inhibitors Enable Chemoproteomic Mapping of Its Endogenous Post-translational Modifications. 34985906 9 41 dep tools 1496:1500 arg1 decipher 1505:1512 decipher 1505:1512 to decipher the mechanisms by which OGA is regulated and directed to its diverse cellular substrates 1502:1601 We expect that these inhibitors and chemoproteomics probes will prove useful as fundamental tools to decipher the mechanisms by which OGA is regulated and directed to its diverse cellular substrates. 34985906 3 42 theme deep 529:532 arg1 cleft 546:550 a deep active site cleft 527:550 a deep active site cleft in which diverse substrates are accommodated 527:595 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 3 43 theme enzymes 458:464 arg1 One 445:447 One 445:447 One 445:447 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 3 43 theme enzymes 458:464 arg1 enzymes 458:464 these enzymes 452:464 these enzymes 452:464 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 0 44 theme Chemoproteomic 41:54 arg1 Mapping 56:62 Chemoproteomic Mapping 41:62 Chemoproteomic Mapping of Its Endogenous Post-translational Modifications 41:113 Bicyclic Picomolar OGA Inhibitors Enable Chemoproteomic Mapping of Its Endogenous Post-translational Modifications. 34985906 5 45 theme superb 833:838 arg1 selectivity 840:850 superb selectivity 833:850 superb selectivity 833:850 Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. 34985906 4 46 theme control 616:622 arg1 OGA 624:626 control OGA 616:626 control OGA 616:626 Chemical tools to control OGA are emerging as essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway. 34985906 6 47 theme site 1046:1049 arg1 cleft 1051:1055 the enzyme active site cleft 1028:1055 the enzyme active site cleft 1028:1055 Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. 34985906 3 48 theme diverse 561:567 arg1 substrates 569:578 diverse substrates 561:578 diverse substrates 561:578 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 1 49 theme mitochondrial 210:222 arg1 proteins 224:231 nuclear, cytoplasmic, and mitochondrial proteins 184:231 nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) 184:285 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 7 50 theme affinity 1102:1109 arg1 probe 1126:1130 a high affinity chemoproteomic probe 1095:1130 a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications 1095:1272 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 5 51 theme human 880:884 arg1 OGA 886:888 human OGA 880:888 human OGA 880:888 Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. 34985906 8 52 theme new 1305:1307 arg1 modifications 1309:1321 new modifications 1305:1321 new modifications 1305:1321 These data uncover a range of new modifications, including some that are less-known, such as O-ubiquitination and N-formylation. 34985906 8 52 theme new 1305:1307 arg1 some 1334:1337 some 1334:1337 some 1334:1337 These data uncover a range of new modifications, including some that are less-known, such as O-ubiquitination and N-formylation. 34985906 6 53 with complex 925:931 arg1 OGA 944:946 human OGA 938:946 human OGA 938:946 Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. 34985906 1 54 theme great 313:317 arg1 interest 319:326 great interest 313:326 great interest 313:326 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 7 55 theme modifications 1260:1272 arg1 mapping 1226:1232 targeted proteomic mapping 1207:1232 targeted proteomic mapping of its post-translational modifications 1207:1272 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 7 55 theme modifications 1260:1272 arg1 purification 1161:1172 simple one-step purification 1145:1172 simple one-step purification of endogenous OGA from brain 1145:1201 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 7 56 from brain 1197:1201 arg1 mapping 1226:1232 targeted proteomic mapping 1207:1232 targeted proteomic mapping of its post-translational modifications 1207:1272 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 7 56 from brain 1197:1201 arg1 purification 1161:1172 simple one-step purification 1145:1172 simple one-step purification of endogenous OGA from brain 1145:1201 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 10 57 theme active 1780:1785 arg1 enzymes 1787:1793 other carbohydrate active enzymes 1761:1793 other carbohydrate active enzymes 1761:1793 Moreover, the inhibitors and structures described here lay out a blueprint that will enable the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes. 34985906 10 58 theme other 1761:1765 arg1 enzymes 1787:1793 other carbohydrate active enzymes 1761:1793 other carbohydrate active enzymes 1761:1793 Moreover, the inhibitors and structures described here lay out a blueprint that will enable the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes. 34985906 1 59 theme interest 319:326 arg1 topic 304:308 a topic 302:308 a topic of great interest 302:326 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 7 60 theme post-translational 1241:1258 arg1 modifications 1260:1272 its post-translational modifications 1237:1272 its post-translational modifications 1237:1272 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 1 61 theme human 138:142 arg1 health 144:149 human health 138:149 human health 138:149 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 10 62 theme carbohydrate 1767:1778 arg1 enzymes 1787:1793 other carbohydrate active enzymes 1761:1793 other carbohydrate active enzymes 1761:1793 Moreover, the inhibitors and structures described here lay out a blueprint that will enable the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes. 34985906 1 63 theme proteins 224:231 arg1 modification 168:179 the modification 164:179 the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) 164:285 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 10 64 theme tools 1732:1736 arg1 creation 1700:1707 the creation 1696:1707 the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes 1696:1793 Moreover, the inhibitors and structures described here lay out a blueprint that will enable the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes. 34985906 8 65 theme modifications 1309:1321 arg1 range 1296:1300 a range 1294:1300 a range of new modifications, including some that are less-known, such as O-ubiquitination and N-formylation 1294:1401 These data uncover a range of new modifications, including some that are less-known, such as O-ubiquitination and N-formylation. 34985906 8 65 theme modifications 1309:1321 arg1 some 1334:1337 some 1334:1337 some 1334:1337 These data uncover a range of new modifications, including some that are less-known, such as O-ubiquitination and N-formylation. 34985906 4 66 theme essential 644:652 arg1 resources 654:662 essential resources 644:662 essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway 644:747 Chemical tools to control OGA are emerging as essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway. 34985906 4 67 theme biochemical 690:700 arg1 functions 715:723 the biochemical and cellular functions 686:723 the biochemical and cellular functions of the O-GlcNAc pathway 686:747 Chemical tools to control OGA are emerging as essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway. 34985906 0 68 theme Endogenous 71:80 arg1 Modifications 101:113 Its Endogenous Post-translational Modifications 67:113 Its Endogenous Post-translational Modifications 67:113 Bicyclic Picomolar OGA Inhibitors Enable Chemoproteomic Mapping of Its Endogenous Post-translational Modifications. 34985906 9 69 theme fundamental 1484:1494 arg1 tools 1496:1500 fundamental tools 1484:1500 fundamental tools to decipher the mechanisms by which OGA is regulated and directed to its diverse cellular substrates 1484:1601 We expect that these inhibitors and chemoproteomics probes will prove useful as fundamental tools to decipher the mechanisms by which OGA is regulated and directed to its diverse cellular substrates. 34985906 6 70 theme enzyme 1032:1037 arg1 cleft 1051:1055 the enzyme active site cleft 1028:1055 the enzyme active site cleft 1028:1055 Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. 34985906 5 71 theme OGA 886:888 arg1 selectivity 840:850 superb selectivity 833:850 superb selectivity 833:850 Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. 34985906 5 71 theme OGA 886:888 arg1 inhibition 866:875 picomolar inhibition 856:875 picomolar inhibition of human OGA 856:888 Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. 34985906 5 72 theme picomolar 856:864 arg1 inhibition 866:875 picomolar inhibition 856:875 picomolar inhibition of human OGA 856:888 Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. 34985906 1 73 theme O-linked 238:245 arg1 O-GlcNAc 277:284 O-GlcNAc 277:284 O-GlcNAc 277:284 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 1 73 theme O-linked 238:245 arg1 residues 267:274 O-linked N-acetylglucosamine residues 238:274 O-linked N-acetylglucosamine residues (O-GlcNAc) 238:285 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 7 74 theme proteomic 1216:1224 arg1 mapping 1226:1232 targeted proteomic mapping 1207:1232 targeted proteomic mapping of its post-translational modifications 1207:1272 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 7 75 theme simple 1145:1150 arg1 purification 1161:1172 simple one-step purification 1145:1172 simple one-step purification of endogenous OGA from brain 1145:1201 Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. 34985906 1 76 with proteins 224:231 arg1 O-GlcNAc 277:284 O-GlcNAc 277:284 O-GlcNAc 277:284 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 1 76 with proteins 224:231 arg1 residues 267:274 O-linked N-acetylglucosamine residues 238:274 O-linked N-acetylglucosamine residues (O-GlcNAc) 238:285 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 3 77 theme dimeric 490:496 arg1 hydrolase 508:516 a dimeric glycoside hydrolase 488:516 a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated 488:595 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 3 77 theme dimeric 490:496 arg1 O-GlcNAcase 469:479 O-GlcNAcase 469:479 O-GlcNAcase (OGA) 469:485 One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. 34985906 6 78 theme human 938:942 arg1 OGA 944:946 human OGA 938:946 human OGA 938:946 Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. 34985906 1 79 theme N-acetylglucosamine 247:265 arg1 O-GlcNAc 277:284 O-GlcNAc 277:284 O-GlcNAc 277:284 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 34985906 1 79 theme N-acetylglucosamine 247:265 arg1 residues 267:274 O-linked N-acetylglucosamine residues 238:274 O-linked N-acetylglucosamine residues (O-GlcNAc) 238:285 Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. 35733260 8 0 theme genes 1429:1433 arg1 induction 1396:1404 the RNA virus-triggered induction 1372:1404 the RNA virus-triggered induction of downstream effector genes 1372:1433 Consistently, TNKS1, TNKS2, or RNF146 deficiency increased the RNA virus-triggered induction of downstream effector genes and impaired the replication of the virus. 35733260 7 1 theme K48-linked 1205:1214 arg1 polyubiquitination 1216:1233 K48-linked polyubiquitination 1205:1233 K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) 1205:1283 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 1 2 theme innate 260:265 arg1 response 274:281 an antiviral innate immune response 247:281 an antiviral innate immune response 247:281 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 1 3 theme virus-induced 345:357 arg1 adaptor 366:372 virus-induced signal adaptor 345:372 virus-induced signal adaptor 345:372 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 10 4 theme harmful 1844:1850 arg1 response 1859:1866 excessive harmful immune response 1834:1866 excessive harmful immune response 1834:1866 Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response. 35733260 1 5 theme viral 171:175 arg1 RNA 177:179 viral RNA 171:179 viral RNA 171:179 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 1 6 theme immune 267:272 arg1 response 274:281 an antiviral innate immune response 247:281 an antiviral innate immune response 247:281 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 1 7 theme signal 359:364 arg1 adaptor 366:372 virus-induced signal adaptor 345:372 virus-induced signal adaptor 345:372 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 8 8 theme virus-triggered 1380:1394 arg1 induction 1396:1404 the RNA virus-triggered induction 1372:1404 the RNA virus-triggered induction of downstream effector genes 1372:1433 Consistently, TNKS1, TNKS2, or RNF146 deficiency increased the RNA virus-triggered induction of downstream effector genes and impaired the replication of the virus. 35733260 0 9 theme RNF146-mediated 88:102 arg1 ubiquitination 104:117 RNF146-mediated ubiquitination 88:117 RNF146-mediated ubiquitination 88:117 Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation. 35733260 10 10 theme innate 1771:1776 arg1 signaling 1785:1793 virus-triggered innate immune signaling 1755:1793 virus-triggered innate immune signaling 1755:1793 Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response. 35733260 5 11 theme VISA-associated 947:961 arg1 tankyrase 922:930 tankyrase 1 922:932 tankyrase 1 (TNKS1) 922:940 Using a biochemical purification approach, we identified tankyrase 1 (TNKS1) as a VISA-associated protein. 35733260 5 11 theme VISA-associated 947:961 arg1 protein 963:969 a VISA-associated protein 945:969 a VISA-associated protein 945:969 Using a biochemical purification approach, we identified tankyrase 1 (TNKS1) as a VISA-associated protein. 35733260 3 12 theme PTMs 665:668 arg1 forms 656:660 other forms 650:660 other forms of PTMs 650:668 However, whether other forms of PTMs regulate VISA-mediated innate immune signaling remains elusive. 35733260 8 13 theme downstream 1409:1418 arg1 genes 1429:1433 downstream effector genes 1409:1433 downstream effector genes 1409:1433 Consistently, TNKS1, TNKS2, or RNF146 deficiency increased the RNA virus-triggered induction of downstream effector genes and impaired the replication of the virus. 35733260 6 14 theme Viral 972:976 arg1 infection 978:986 Viral infection 972:986 Viral infection 972:986 Viral infection led to the induction of TNKS1 and its homolog TNKS2, which translocated from cytosol to mitochondria and interacted with VISA. 35733260 9 15 theme virus 1644:1648 arg1 loads 1650:1654 markedly reduced virus loads 1627:1654 markedly reduced virus loads 1627:1654 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 9 16 theme higher 1528:1533 arg1 levels 1535:1540 higher levels 1528:1540 higher levels of type I interferons (IFNs) and proinflammatory cytokines 1528:1599 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 1 17 theme RNA 177:179 arg1 sensing 160:166 sensing 160:166 sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) 160:235 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 7 18 theme Glu137 1166:1171 arg1 residue 1173:1179 Glu137 residue 1166:1179 Glu137 residue 1166:1179 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 10 19 theme essential 1715:1723 arg1 role 1725:1728 an essential role 1712:1728 an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response 1712:1866 Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response. 35733260 4 20 theme immune 833:838 arg1 response 840:847 innate immune response 826:847 innate immune response to RNA viruses 826:862 Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. 35733260 9 21 theme proinflammatory 1575:1589 arg1 cytokines 1591:1599 proinflammatory cytokines 1575:1599 proinflammatory cytokines 1575:1599 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 3 22 theme VISA-mediated 679:691 arg1 signaling 707:715 VISA-mediated innate immune signaling 679:715 VISA-mediated innate immune signaling 679:715 However, whether other forms of PTMs regulate VISA-mediated innate immune signaling remains elusive. 35733260 4 23 theme RNA 852:854 arg1 viruses 856:862 RNA viruses 852:862 RNA viruses 852:862 Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. 35733260 10 24 theme VISA 1747:1750 arg1 PARylation 1733:1742 PARylation 1733:1742 PARylation of VISA 1733:1750 Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response. 35733260 2 25 link O-linked 554:561 arg1 O-GlcNAcylation 594:608 O-GlcNAcylation 594:608 O-GlcNAcylation 594:608 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 25 link O-linked 554:561 arg1 β-d-N-acetylglucosaminylation 563:591 O-linked β-d-N-acetylglucosaminylation 554:591 O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation) 554:609 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 1 26 theme retinoic 184:191 arg1 receptors 220:228 retinoic acid-inducible gene-I-like receptors 184:228 retinoic acid-inducible gene-I-like receptors (RLRs) 184:235 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 1 26 theme retinoic 184:191 arg1 RLRs 231:234 RLRs 231:234 RLRs 231:234 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 7 27 theme VISA 1158:1161 arg1 PARylation 1144:1153 the PARylation 1140:1153 the PARylation of VISA at Glu137 residue 1140:1179 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 10 28 theme virus-triggered 1755:1769 arg1 signaling 1785:1793 virus-triggered innate immune signaling 1755:1793 virus-triggered innate immune signaling 1755:1793 Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response. 35733260 9 29 theme cytokines 1591:1599 arg1 levels 1535:1540 higher levels 1528:1540 higher levels of type I interferons (IFNs) and proinflammatory cytokines 1528:1599 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 9 30 theme type 1545:1548 arg1 IFNs 1565:1568 IFNs 1565:1568 IFNs 1565:1568 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 9 30 theme type 1545:1548 arg1 interferons 1552:1562 type I interferons 1545:1562 type I interferons (IFNs) 1545:1569 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 1 31 theme acid-inducible 193:206 arg1 receptors 220:228 retinoic acid-inducible gene-I-like receptors 184:228 retinoic acid-inducible gene-I-like receptors (RLRs) 184:235 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 1 31 theme acid-inducible 193:206 arg1 RLRs 231:234 RLRs 231:234 RLRs 231:234 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 0 32 theme antiviral 26:34 arg1 response 36:43 innate antiviral response 19:43 innate antiviral response 19:43 Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation. 35733260 7 33 link K48-linked 1205:1214 arg1 polyubiquitination 1216:1233 K48-linked polyubiquitination 1205:1233 K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) 1205:1283 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 9 34 theme I 1550:1550 arg1 IFNs 1565:1568 IFNs 1565:1568 IFNs 1565:1568 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 9 34 theme I 1550:1550 arg1 interferons 1552:1562 type I interferons 1545:1562 type I interferons (IFNs) 1545:1569 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 1 35 theme gene-I-like 208:218 arg1 receptors 220:228 retinoic acid-inducible gene-I-like receptors 184:228 retinoic acid-inducible gene-I-like receptors (RLRs) 184:235 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 1 35 theme gene-I-like 208:218 arg1 RLRs 231:234 RLRs 231:234 RLRs 231:234 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 0 36 theme innate 19:24 arg1 response 36:43 innate antiviral response 19:43 innate antiviral response 19:43 Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation. 35733260 1 37 dep VISA 339:342 arg1 known 380:384 known 380:384 known as mitochondrial antiviral signaling protein [MAVS 380:435 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 2 38 theme O-linked 554:561 arg1 O-GlcNAcylation 594:608 O-GlcNAcylation 594:608 O-GlcNAcylation 594:608 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 38 theme O-linked 554:561 arg1 β-d-N-acetylglucosaminylation 563:591 O-linked β-d-N-acetylglucosaminylation 554:591 O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation) 554:609 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 8 39 theme effector 1420:1427 arg1 genes 1429:1433 downstream effector genes 1409:1433 downstream effector genes 1409:1433 Consistently, TNKS1, TNKS2, or RNF146 deficiency increased the RNA virus-triggered induction of downstream effector genes and impaired the replication of the virus. 35733260 9 40 theme interferons 1552:1562 arg1 levels 1535:1540 higher levels 1528:1540 higher levels of type I interferons (IFNs) and proinflammatory cytokines 1528:1599 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 9 41 theme TNKS2-deficient 1498:1512 arg1 mice 1514:1517 TNKS1- or TNKS2-deficient mice 1488:1517 TNKS1- or TNKS2-deficient mice 1488:1517 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 6 42 theme homolog 1026:1032 arg1 TNKS2 1034:1038 its homolog TNKS2 1022:1038 its homolog TNKS2 1022:1038 Viral infection led to the induction of TNKS1 and its homolog TNKS2, which translocated from cytosol to mitochondria and interacted with VISA. 35733260 1 43 theme mitochondrial 389:401 arg1 [MAVS 431:435 mitochondrial antiviral signaling protein [MAVS 389:435 mitochondrial antiviral signaling protein [MAVS 389:435 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 10 44 theme immune 1778:1783 arg1 signaling 1785:1793 virus-triggered innate immune signaling 1755:1793 virus-triggered innate immune signaling 1755:1793 Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response. 35733260 2 45 theme posttranslational 469:485 arg1 polyubiquitination 517:534 polyubiquitination 517:534 polyubiquitination 517:534 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 45 theme posttranslational 469:485 arg1 PTMs 502:505 PTMs 502:505 PTMs 502:505 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 45 theme posttranslational 469:485 arg1 phosphorylation 537:551 phosphorylation 537:551 phosphorylation 537:551 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 45 theme posttranslational 469:485 arg1 β-d-N-acetylglucosaminylation 563:591 O-linked β-d-N-acetylglucosaminylation 554:591 O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation) 554:609 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 45 theme posttranslational 469:485 arg1 monomethylation 616:630 monomethylation 616:630 monomethylation 616:630 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 45 theme posttranslational 469:485 arg1 modifications 487:499 various posttranslational modifications 461:499 various posttranslational modifications (PTMs) 461:506 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 1 46 theme antiviral 403:411 arg1 [MAVS 431:435 mitochondrial antiviral signaling protein [MAVS 389:435 mitochondrial antiviral signaling protein [MAVS 389:435 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 8 47 theme RNF146 1344:1349 arg1 deficiency 1351:1360 RNF146 deficiency 1344:1360 RNF146 deficiency 1344:1360 Consistently, TNKS1, TNKS2, or RNF146 deficiency increased the RNA virus-triggered induction of downstream effector genes and impaired the replication of the virus. 35733260 2 48 theme various 461:467 arg1 polyubiquitination 517:534 polyubiquitination 517:534 polyubiquitination 517:534 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 48 theme various 461:467 arg1 PTMs 502:505 PTMs 502:505 PTMs 502:505 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 48 theme various 461:467 arg1 phosphorylation 537:551 phosphorylation 537:551 phosphorylation 537:551 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 48 theme various 461:467 arg1 β-d-N-acetylglucosaminylation 563:591 O-linked β-d-N-acetylglucosaminylation 554:591 O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation) 554:609 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 48 theme various 461:467 arg1 monomethylation 616:630 monomethylation 616:630 monomethylation 616:630 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 2 48 theme various 461:467 arg1 modifications 487:499 various posttranslational modifications 461:499 various posttranslational modifications (PTMs) 461:506 VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked β-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. 35733260 1 49 theme mitochondrial 309:321 arg1 VISA 339:342 the mitochondrial adaptor protein VISA 305:342 the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]) 305:437 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 1 50 theme signaling 413:421 arg1 [MAVS 431:435 mitochondrial antiviral signaling protein [MAVS 389:435 mitochondrial antiviral signaling protein [MAVS 389:435 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 4 51 theme innate 826:831 arg1 response 840:847 innate immune response 826:847 innate immune response to RNA viruses 826:862 Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. 35733260 7 52 theme Ring 1252:1255 arg1 protein 1264:1270 the E3 ligase Ring figure protein 146 1238:1274 the E3 ligase Ring figure protein 146 (RNF146) 1238:1283 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 7 52 theme Ring 1252:1255 arg1 RNF146 1277:1282 RNF146 1277:1282 RNF146 1277:1282 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 1 53 theme adaptor 323:329 arg1 VISA 339:342 the mitochondrial adaptor protein VISA 305:342 the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]) 305:437 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 1 54 theme protein 423:429 arg1 [MAVS 431:435 mitochondrial antiviral signaling protein [MAVS 389:435 mitochondrial antiviral signaling protein [MAVS 389:435 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 10 55 theme immune 1852:1857 arg1 response 1859:1866 excessive harmful immune response 1834:1866 excessive harmful immune response 1834:1866 Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response. 35733260 9 56 theme reduced 1636:1642 arg1 loads 1650:1654 markedly reduced virus loads 1627:1654 markedly reduced virus loads 1627:1654 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 7 57 theme figure 1257:1262 arg1 protein 1264:1270 the E3 ligase Ring figure protein 146 1238:1274 the E3 ligase Ring figure protein 146 (RNF146) 1238:1283 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 7 57 theme figure 1257:1262 arg1 RNF146 1277:1282 RNF146 1277:1282 RNF146 1277:1282 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 1 58 dep known 380:384 arg1 also 375:378 also 375:378 also 375:378 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 1 59 theme protein 331:337 arg1 VISA 339:342 the mitochondrial adaptor protein VISA 305:342 the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]) 305:437 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 7 60 theme subsequent 1289:1298 arg1 degradation 1300:1310 subsequent degradation 1289:1310 subsequent degradation 1289:1310 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 3 61 theme other 650:654 arg1 forms 656:660 other forms 650:660 other forms of PTMs 650:668 However, whether other forms of PTMs regulate VISA-mediated innate immune signaling remains elusive. 35733260 9 62 theme TNKS1- 1488:1493 arg1 mice 1514:1517 TNKS1- or TNKS2-deficient mice 1488:1517 TNKS1- or TNKS2-deficient mice 1488:1517 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 1 63 theme viral 143:147 arg1 infection 149:157 viral infection 143:157 viral infection 143:157 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35733260 10 64 theme PARylation 1733:1742 arg1 role 1725:1728 an essential role 1712:1728 an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response 1712:1866 Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response. 35733260 6 65 theme TNKS1 1012:1016 arg1 induction 999:1007 the induction 995:1007 the induction 995:1007 Viral infection led to the induction of TNKS1 and its homolog TNKS2, which translocated from cytosol to mitochondria and interacted with VISA. 35733260 7 66 from residue 1173:1179 arg1 PARylation 1144:1153 the PARylation 1140:1153 the PARylation of VISA at Glu137 residue 1140:1179 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 3 67 theme innate 693:698 arg1 signaling 707:715 VISA-mediated innate immune signaling 679:715 VISA-mediated innate immune signaling 679:715 However, whether other forms of PTMs regulate VISA-mediated innate immune signaling remains elusive. 35733260 8 68 theme RNA 1376:1378 arg1 induction 1396:1404 the RNA virus-triggered induction 1372:1404 the RNA virus-triggered induction of downstream effector genes 1372:1433 Consistently, TNKS1, TNKS2, or RNF146 deficiency increased the RNA virus-triggered induction of downstream effector genes and impaired the replication of the virus. 35733260 7 69 theme ligase 1245:1250 arg1 protein 1264:1270 the E3 ligase Ring figure protein 146 1238:1274 the E3 ligase Ring figure protein 146 (RNF146) 1238:1283 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 7 69 theme ligase 1245:1250 arg1 RNF146 1277:1282 RNF146 1277:1282 RNF146 1277:1282 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 10 70 from role 1725:1728 arg1 signaling 1785:1793 virus-triggered innate immune signaling 1755:1793 virus-triggered innate immune signaling 1755:1793 Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response. 35733260 4 71 theme Poly 755:758 arg1 PARylation 779:788 PARylation 779:788 PARylation 779:788 Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. 35733260 4 71 theme Poly 755:758 arg1 ation  772:777 Poly(ADP-ribosyl)ation  755:777 Poly(ADP-ribosyl)ation (PARylation) 755:789 Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. 35733260 4 71 theme Poly 755:758 arg1 PTM 796:798 a PTM 794:798 a PTM 794:798 Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. 35733260 3 72 theme immune 700:705 arg1 signaling 707:715 VISA-mediated innate immune signaling 679:715 VISA-mediated innate immune signaling 679:715 However, whether other forms of PTMs regulate VISA-mediated innate immune signaling remains elusive. 35733260 4 73 theme VISA 803:806 arg1 ation  772:777 Poly(ADP-ribosyl)ation  755:777 Poly(ADP-ribosyl)ation (PARylation) 755:789 Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. 35733260 4 73 theme VISA 803:806 arg1 PTM 796:798 a PTM 794:798 a PTM 794:798 Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. 35733260 6 74 theme TNKS2 1034:1038 arg1 induction 999:1007 the induction 995:1007 the induction 995:1007 Viral infection led to the induction of TNKS1 and its homolog TNKS2, which translocated from cytosol to mitochondria and interacted with VISA. 35733260 5 75 theme biochemical 873:883 arg1 approach 898:905 a biochemical purification approach 871:905 a biochemical purification approach 871:905 Using a biochemical purification approach, we identified tankyrase 1 (TNKS1) as a VISA-associated protein. 35733260 10 76 theme excessive 1834:1842 arg1 response 1859:1866 excessive harmful immune response 1834:1866 excessive harmful immune response 1834:1866 Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response. 35733260 8 77 theme virus 1471:1475 arg1 replication 1452:1462 the replication 1448:1462 the replication of the virus 1448:1475 Consistently, TNKS1, TNKS2, or RNF146 deficiency increased the RNA virus-triggered induction of downstream effector genes and impaired the replication of the virus. 35733260 9 78 theme virus 1607:1611 arg1 infection 1613:1621 virus infection 1607:1621 virus infection 1607:1621 Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. 35733260 7 79 theme E3 1242:1243 arg1 protein 1264:1270 the E3 ligase Ring figure protein 146 1238:1274 the E3 ligase Ring figure protein 146 (RNF146) 1238:1283 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 7 79 theme E3 1242:1243 arg1 RNF146 1277:1282 RNF146 1277:1282 RNF146 1277:1282 TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. 35733260 5 80 theme purification 885:896 arg1 approach 898:905 a biochemical purification approach 871:905 a biochemical purification approach 871:905 Using a biochemical purification approach, we identified tankyrase 1 (TNKS1) as a VISA-associated protein. 35733260 1 81 theme antiviral 250:258 arg1 response 274:281 an antiviral innate immune response 247:281 an antiviral innate immune response 247:281 During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). 35644283 12 0 theme ADPKD 1981:1985 arg1 feature 1970:1976 a pathological feature 1955:1976 a pathological feature of ADPKD 1955:1985 Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a pathological feature of ADPKD. 35644283 12 0 theme ADPKD 1981:1985 arg1 levels 1874:1879 elevated levels 1865:1879 elevated levels 1865:1879 Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a pathological feature of ADPKD. 35644283 6 1 theme O-linked 1030:1037 arg1 β-N-acetylglucosamine 1039:1059 O-linked β-N-acetylglucosamine 1030:1059 O-linked β-N-acetylglucosamine (O-GlcNAc) 1030:1070 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 1 theme O-linked 1030:1037 arg1 O-GlcNAc 1062:1069 O-GlcNAc 1062:1069 O-GlcNAc 1062:1069 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 1 theme O-linked 1030:1037 arg1 sensor 1022:1027 the nutrient sensor 1009:1027 the nutrient sensor 1009:1027 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 4 2 theme potential 580:588 arg1 value 602:606 potential therapeutic value 580:606 potential therapeutic value 580:606 These studies indicate that dysfunction of specific cilia components has potential therapeutic value. 35644283 2 3 theme polycystic 369:378 arg1 ADPKD 396:400 ADPKD 396:400 ADPKD 396:400 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 2 3 theme polycystic 369:378 arg1 disease 387:393 autosomal dominant polycystic kidney disease 350:393 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 5 4 theme potential 679:687 arg1 understanding 624:636 our understanding 620:636 our understanding of cilia dysfunction and its therapeutic potential 620:687 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 11 5 theme ADPKD 1836:1840 arg1 pathobiology 1842:1853 ADPKD pathobiology 1836:1853 ADPKD pathobiology 1836:1853 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 2 6 theme kidney 298:303 arg1 PKD 314:316 PKD 314:316 PKD 314:316 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 2 6 theme kidney 298:303 arg1 disease 305:311 polycystic kidney disease 287:311 polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 287:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 8 7 from deletion 1340:1347 arg1 mice 1364:1367 adult ADPKD mice 1352:1367 adult ADPKD mice 1352:1367 In contrast, Ttc21b deletion in adult ADPKD mice markedly attenuated kidney cystogenesis and reduced cilia length, inflammation, and O-GlcNAc levels. 35644283 1 8 theme intraflagellar 189:202 arg1 transport 204:212 intraflagellar transport 189:212 intraflagellar transport (IFT) multiprotein complexes 189:241 Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes. 35644283 1 8 theme intraflagellar 189:202 arg1 IFT 215:217 IFT 215:217 IFT 215:217 Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes. 35644283 6 9 theme adult 841:845 arg1 mice 873:876 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice 804:876 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice 804:876 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 10 dep juvenile 809:816 arg1 day 829:831 postnatal day 21 819:834 postnatal day 21 819:834 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 11 11 theme distinct 1739:1746 arg1 segments 1756:1763 distinct nephron segments 1739:1763 distinct nephron segments 1739:1763 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 5 12 theme dysfunction 647:657 arg1 understanding 624:636 our understanding 620:636 our understanding of cilia dysfunction and its therapeutic potential 620:687 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 6 13 theme kidney 912:917 arg1 cilia 964:968 lengthened kidney cilia 946:968 lengthened kidney cilia 946:968 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 13 theme kidney 912:917 arg1 ratios 938:943 kidney weight/body weight ratios 912:943 kidney weight/body weight ratios 912:943 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 13 theme kidney 912:917 arg1 inflammation 971:982 inflammation 971:982 inflammation 971:982 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 11 14 theme ciliary 1812:1818 arg1 homeostasis 1820:1830 ciliary homeostasis 1812:1830 ciliary homeostasis 1812:1830 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 8 15 theme kidney 1389:1394 arg1 cystogenesis 1396:1407 kidney cystogenesis 1389:1407 kidney cystogenesis 1389:1407 In contrast, Ttc21b deletion in adult ADPKD mice markedly attenuated kidney cystogenesis and reduced cilia length, inflammation, and O-GlcNAc levels. 35644283 5 16 theme deletion 724:731 arg1 role 709:712 the role 705:712 the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD 705:801 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 5 17 theme ADPKD 797:801 arg1 models 787:792 juvenile and adult mouse models 762:792 juvenile and adult mouse models of ADPKD 762:801 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 6 18 theme kidney 888:893 arg1 cysts 895:899 kidney cysts 888:899 kidney cysts 888:899 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 8 19 theme cilia 1421:1425 arg1 length 1427:1432 cilia length 1421:1432 cilia length 1421:1432 In contrast, Ttc21b deletion in adult ADPKD mice markedly attenuated kidney cystogenesis and reduced cilia length, inflammation, and O-GlcNAc levels. 35644283 7 20 theme Ttc21b 1085:1090 arg1 Deletion 1073:1080 Deletion 1073:1080 Deletion of Ttc21b in juvenile ADPKD mice 1073:1113 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 7 21 theme O-GlcNAc 1303:1310 arg1 levels 1312:1317 O-GlcNAc levels 1303:1317 O-GlcNAc levels 1303:1317 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 1 22 theme sensory 146:152 arg1 cilia 136:140 Primary cilia 128:140 Primary cilia 128:140 Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes. 35644283 1 22 theme sensory 146:152 arg1 organelles 154:163 sensory organelles 146:163 sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes 146:241 Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes. 35644283 2 23 theme IFT-B 264:268 arg1 genes 270:274 several IFT-B genes 256:274 several IFT-B genes 256:274 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 2 24 from severity 319:326 arg1 models 409:414 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 6 25 theme kidney 957:962 arg1 cilia 964:968 lengthened kidney cilia 946:968 lengthened kidney cilia 946:968 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 25 theme kidney 957:962 arg1 ratios 938:943 kidney weight/body weight ratios 912:943 kidney weight/body weight ratios 912:943 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 7 26 theme weight/body 1172:1182 arg1 ratios 1191:1196 kidney weight/body weight ratios 1165:1196 kidney weight/body weight ratios 1165:1196 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 8 27 theme O-GlcNAc 1453:1460 arg1 levels 1462:1467 O-GlcNAc levels 1453:1467 O-GlcNAc levels 1453:1467 In contrast, Ttc21b deletion in adult ADPKD mice markedly attenuated kidney cystogenesis and reduced cilia length, inflammation, and O-GlcNAc levels. 35644283 11 28 theme different 1692:1700 arg1 factors 1721:1727 different microenvironmental factors 1692:1727 different microenvironmental factors 1692:1727 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 6 29 theme weight 931:936 arg1 cilia 964:968 lengthened kidney cilia 946:968 lengthened kidney cilia 946:968 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 29 theme weight 931:936 arg1 ratios 938:943 kidney weight/body weight ratios 912:943 kidney weight/body weight ratios 912:943 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 29 theme weight 931:936 arg1 inflammation 971:982 inflammation 971:982 inflammation 971:982 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 3 30 theme IFT-A 441:445 arg1 Tulp3 456:460 Tulp3 456:460 Tulp3 456:460 However, deletion of an IFT-A adaptor, Tulp3, attenuates PKD severity in adult mice only. 35644283 3 30 theme IFT-A 441:445 arg1 adaptor 447:453 an IFT-A adaptor 438:453 an IFT-A adaptor 438:453 However, deletion of an IFT-A adaptor, Tulp3, attenuates PKD severity in adult mice only. 35644283 7 31 theme duct 1143:1146 arg1 cystogenesis 1148:1159 cortical collecting duct cystogenesis 1123:1159 cortical collecting duct cystogenesis 1123:1159 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 0 32 theme polycystic 48:57 arg1 disease 66:72 autosomal dominant polycystic kidney disease 29:72 autosomal dominant polycystic kidney disease 29:72 Ttc21b deficiency attenuates autosomal dominant polycystic kidney disease in a kidney tubular- and maturation-dependent manner. 35644283 6 33 theme nutrient 1013:1020 arg1 β-N-acetylglucosamine 1039:1059 O-linked β-N-acetylglucosamine 1030:1059 O-linked β-N-acetylglucosamine (O-GlcNAc) 1030:1070 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 33 theme nutrient 1013:1020 arg1 sensor 1022:1027 the nutrient sensor 1009:1027 the nutrient sensor 1009:1027 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 10 34 theme IFT-A 1580:1584 arg1 adaptor 1586:1592 an IFT-A adaptor 1577:1592 an IFT-A adaptor 1577:1592 Unlike an IFT-A adaptor, deleting Ttc21b in juvenile ADPKD mice is partially ameliorative. 35644283 0 35 theme Ttc21b 0:5 arg1 deficiency 7:16 Ttc21b deficiency 0:16 Ttc21b deficiency 0:16 Ttc21b deficiency attenuates autosomal dominant polycystic kidney disease in a kidney tubular- and maturation-dependent manner. 35644283 9 36 theme Ttc21b 1504:1509 arg1 deletion 1511:1518 Ttc21b deletion 1504:1518 Ttc21b deletion 1504:1518 Thus, unlike IFT-B, the effect of Ttc21b deletion in mouse models of ADPKD is development-specific. 35644283 1 37 dep organelles 154:163 arg1 built 165:169 built 165:169 built 165:169 Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes. 35644283 1 37 dep organelles 154:163 arg1 maintained 175:184 maintained 175:184 maintained by intraflagellar transport (IFT) multiprotein complexes 175:241 Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes. 35644283 10 38 theme juvenile 1614:1621 arg1 mice 1629:1632 juvenile ADPKD mice 1614:1632 juvenile ADPKD mice 1614:1632 Unlike an IFT-A adaptor, deleting Ttc21b in juvenile ADPKD mice is partially ameliorative. 35644283 4 39 theme cilia 559:563 arg1 components 565:574 specific cilia components 550:574 specific cilia components 550:574 These studies indicate that dysfunction of specific cilia components has potential therapeutic value. 35644283 7 40 theme cortical 1123:1130 arg1 duct 1143:1146 cortical collecting duct 1123:1146 cortical collecting duct cystogenesis 1123:1159 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 7 41 theme juvenile 1095:1102 arg1 mice 1110:1113 juvenile ADPKD mice 1095:1113 juvenile ADPKD mice 1095:1113 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 0 42 theme dominant 39:46 arg1 disease 66:72 autosomal dominant polycystic kidney disease 29:72 autosomal dominant polycystic kidney disease 29:72 Ttc21b deficiency attenuates autosomal dominant polycystic kidney disease in a kidney tubular- and maturation-dependent manner. 35644283 8 43 theme adult 1352:1356 arg1 mice 1364:1367 adult ADPKD mice 1352:1367 adult ADPKD mice 1352:1367 In contrast, Ttc21b deletion in adult ADPKD mice markedly attenuated kidney cystogenesis and reduced cilia length, inflammation, and O-GlcNAc levels. 35644283 2 44 theme dominant 360:367 arg1 ADPKD 396:400 ADPKD 396:400 ADPKD 396:400 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 2 44 theme dominant 360:367 arg1 disease 387:393 autosomal dominant polycystic kidney disease 350:393 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 5 45 theme mouse 781:785 arg1 models 787:792 juvenile and adult mouse models 762:792 juvenile and adult mouse models of ADPKD 762:801 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 6 46 theme postnatal 819:827 arg1 day 829:831 postnatal day 21 819:834 postnatal day 21 819:834 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 9 47 theme ADPKD 1539:1543 arg1 models 1529:1534 mouse models 1523:1534 mouse models of ADPKD 1523:1543 Thus, unlike IFT-B, the effect of Ttc21b deletion in mouse models of ADPKD is development-specific. 35644283 7 48 from Deletion 1073:1080 arg1 mice 1110:1113 juvenile ADPKD mice 1095:1113 juvenile ADPKD mice 1095:1113 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 2 49 theme adult 344:348 arg1 models 409:414 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 6 50 theme juvenile 809:816 arg1 mice 873:876 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice 804:876 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice 804:876 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 10 51 from Ttc21b 1604:1609 arg1 mice 1629:1632 juvenile ADPKD mice 1614:1632 juvenile ADPKD mice 1614:1632 Unlike an IFT-A adaptor, deleting Ttc21b in juvenile ADPKD mice is partially ameliorative. 35644283 7 52 theme glomerular 1230:1239 arg1 dilations 1241:1249 proximal tubular and glomerular dilations 1209:1249 proximal tubular and glomerular dilations 1209:1249 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 6 53 dep adult 841:845 arg1 months 852:857 six months 848:857 six months of age 848:864 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 10 54 theme deleting 1595:1602 arg1 Ttc21b 1604:1609 deleting Ttc21b 1595:1609 deleting Ttc21b in juvenile ADPKD mice 1595:1632 Unlike an IFT-A adaptor, deleting Ttc21b in juvenile ADPKD mice is partially ameliorative. 35644283 12 55 theme pathological 1957:1968 arg1 feature 1970:1976 a pathological feature 1955:1976 a pathological feature of ADPKD 1955:1985 Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a pathological feature of ADPKD. 35644283 12 55 theme pathological 1957:1968 arg1 levels 1874:1879 elevated levels 1865:1879 elevated levels 1865:1879 Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a pathological feature of ADPKD. 35644283 7 56 theme collecting 1132:1141 arg1 duct 1143:1146 cortical collecting duct 1123:1146 cortical collecting duct cystogenesis 1123:1159 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 7 57 theme tubular 1218:1224 arg1 dilations 1241:1249 proximal tubular and glomerular dilations 1209:1249 proximal tubular and glomerular dilations 1209:1249 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 7 58 theme kidney 1165:1170 arg1 ratios 1191:1196 kidney weight/body weight ratios 1165:1196 kidney weight/body weight ratios 1165:1196 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 2 59 theme kidney 380:385 arg1 ADPKD 396:400 ADPKD 396:400 ADPKD 396:400 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 2 59 theme kidney 380:385 arg1 disease 387:393 autosomal dominant polycystic kidney disease 350:393 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 6 60 theme age 862:864 arg1 months 852:857 six months 848:857 six months of age 848:864 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 5 61 theme therapeutic 667:677 arg1 potential 679:687 its therapeutic potential 663:687 its therapeutic potential 663:687 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 5 62 from role 709:712 arg1 models 787:792 juvenile and adult mouse models 762:792 juvenile and adult mouse models of ADPKD 762:801 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 11 63 theme mature 1790:1795 arg1 stages 1797:1802 mature stages 1790:1802 mature stages 1790:1802 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 4 64 theme therapeutic 590:600 arg1 value 602:606 potential therapeutic value 580:606 potential therapeutic value 580:606 These studies indicate that dysfunction of specific cilia components has potential therapeutic value. 35644283 2 65 theme disease 305:311 arg1 severity 319:326 polycystic kidney disease (PKD) severity 287:326 polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 287:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 0 66 theme kidney 59:64 arg1 disease 66:72 autosomal dominant polycystic kidney disease 29:72 autosomal dominant polycystic kidney disease 29:72 Ttc21b deficiency attenuates autosomal dominant polycystic kidney disease in a kidney tubular- and maturation-dependent manner. 35644283 5 67 theme cilia 641:645 arg1 dysfunction 647:657 cilia dysfunction 641:657 cilia dysfunction 641:657 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 2 68 theme juvenile 331:338 arg1 models 409:414 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 1 69 theme transport 204:212 arg1 complexes 233:241 intraflagellar transport (IFT) multiprotein complexes 189:241 intraflagellar transport (IFT) multiprotein complexes 189:241 Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes. 35644283 12 70 theme cellular 1910:1917 arg1 metabolism 1919:1928 cellular metabolism 1910:1928 cellular metabolism 1910:1928 Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a pathological feature of ADPKD. 35644283 6 71 theme weight/body 919:929 arg1 cilia 964:968 lengthened kidney cilia 946:968 lengthened kidney cilia 946:968 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 71 theme weight/body 919:929 arg1 ratios 938:943 kidney weight/body weight ratios 912:943 kidney weight/body weight ratios 912:943 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 71 theme weight/body 919:929 arg1 inflammation 971:982 inflammation 971:982 inflammation 971:982 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 11 72 theme nephron 1748:1754 arg1 segments 1756:1763 distinct nephron segments 1739:1763 distinct nephron segments 1739:1763 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 11 73 located found 1730:1734 arg1 stages 1797:1802 mature stages 1790:1802 mature stages 1790:1802 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 11 73 located found 1730:1734 arg2 factors 1721:1727 different microenvironmental factors 1692:1727 different microenvironmental factors 1692:1727 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 11 73 located found 1730:1734 arg1 segments 1756:1763 distinct nephron segments 1739:1763 distinct nephron segments 1739:1763 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 11 73 located found 1730:1734 arg1 developing 1772:1781 developing 1772:1781 developing 1772:1781 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 2 74 theme autosomal 350:358 arg1 ADPKD 396:400 ADPKD 396:400 ADPKD 396:400 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 2 74 theme autosomal 350:358 arg1 disease 387:393 autosomal dominant polycystic kidney disease 350:393 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 5 75 theme global 717:722 arg1 deletion 724:731 global deletion 717:731 global deletion of an IFT-A gene, Ttc21b, 717:757 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 2 76 theme several 256:262 arg1 genes 270:274 several IFT-B genes 256:274 several IFT-B genes 256:274 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 1 77 theme multiprotein 220:231 arg1 complexes 233:241 intraflagellar transport (IFT) multiprotein complexes 189:241 intraflagellar transport (IFT) multiprotein complexes 189:241 Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes. 35644283 12 78 theme O-GlcNAc 1884:1891 arg1 feature 1970:1976 a pathological feature 1955:1976 a pathological feature of ADPKD 1955:1985 Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a pathological feature of ADPKD. 35644283 12 78 theme O-GlcNAc 1884:1891 arg1 levels 1874:1879 elevated levels 1865:1879 elevated levels 1865:1879 Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a pathological feature of ADPKD. 35644283 4 79 contain has 576:578 arg1 dysfunction 535:545 dysfunction 535:545 dysfunction of specific cilia components 535:574 These studies indicate that dysfunction of specific cilia components has potential therapeutic value. 35644283 4 79 contain has 576:578 arg2 value 602:606 potential therapeutic value 580:606 potential therapeutic value 580:606 These studies indicate that dysfunction of specific cilia components has potential therapeutic value. 35644283 1 80 theme Primary 128:134 arg1 cilia 136:140 Primary cilia 128:140 Primary cilia 128:140 Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes. 35644283 1 80 theme Primary 128:134 arg1 organelles 154:163 sensory organelles 146:163 sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes 146:241 Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multiprotein complexes. 35644283 7 81 theme ADPKD 1104:1108 arg1 mice 1110:1113 juvenile ADPKD mice 1095:1113 juvenile ADPKD mice 1095:1113 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 2 82 theme polycystic 287:296 arg1 PKD 314:316 PKD 314:316 PKD 314:316 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 2 82 theme polycystic 287:296 arg1 disease 305:311 polycystic kidney disease 287:311 polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 287:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 3 83 theme PKD 474:476 arg1 severity 478:485 PKD severity 474:485 PKD severity 474:485 However, deletion of an IFT-A adaptor, Tulp3, attenuates PKD severity in adult mice only. 35644283 7 84 theme weight 1184:1189 arg1 ratios 1191:1196 kidney weight/body weight ratios 1165:1196 kidney weight/body weight ratios 1165:1196 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 2 85 theme genes 270:274 arg1 Deletion 244:251 Deletion 244:251 Deletion of several IFT-B genes 244:274 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 0 86 theme tubular- 86:93 arg1 manner 120:125 a kidney tubular- and maturation-dependent manner 77:125 a kidney tubular- and maturation-dependent manner 77:125 Ttc21b deficiency attenuates autosomal dominant polycystic kidney disease in a kidney tubular- and maturation-dependent manner. 35644283 12 87 theme elevated 1865:1872 arg1 feature 1970:1976 a pathological feature 1955:1976 a pathological feature of ADPKD 1955:1985 Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a pathological feature of ADPKD. 35644283 12 87 theme elevated 1865:1872 arg1 levels 1874:1879 elevated levels 1865:1879 elevated levels 1865:1879 Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a pathological feature of ADPKD. 35644283 9 88 from effect 1494:1499 arg1 models 1529:1534 mouse models 1523:1534 mouse models of ADPKD 1523:1543 Thus, unlike IFT-B, the effect of Ttc21b deletion in mouse models of ADPKD is development-specific. 35644283 6 89 theme lengthened 946:955 arg1 cilia 964:968 lengthened kidney cilia 946:968 lengthened kidney cilia 946:968 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 89 theme lengthened 946:955 arg1 ratios 938:943 kidney weight/body weight ratios 912:943 kidney weight/body weight ratios 912:943 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 0 90 theme maturation-dependent 99:118 arg1 manner 120:125 a kidney tubular- and maturation-dependent manner 77:125 a kidney tubular- and maturation-dependent manner 77:125 Ttc21b deficiency attenuates autosomal dominant polycystic kidney disease in a kidney tubular- and maturation-dependent manner. 35644283 11 91 theme microenvironmental 1702:1719 arg1 factors 1721:1727 different microenvironmental factors 1692:1727 different microenvironmental factors 1692:1727 Thus, our studies suggest that different microenvironmental factors, found in distinct nephron segments and in developing versus mature stages, modify ciliary homeostasis and ADPKD pathobiology. 35644283 5 92 theme IFT-A 739:743 arg1 Ttc21b 751:756 Ttc21b 751:756 Ttc21b 751:756 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 5 92 theme IFT-A 739:743 arg1 gene 745:748 an IFT-A gene 736:748 an IFT-A gene 736:748 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 6 93 theme sensor 1022:1027 arg1 levels 999:1004 levels 999:1004 levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc) 999:1070 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 3 94 theme adaptor 447:453 arg1 deletion 426:433 deletion 426:433 deletion of an IFT-A adaptor, Tulp3, 426:461 However, deletion of an IFT-A adaptor, Tulp3, attenuates PKD severity in adult mice only. 35644283 7 95 theme cilia 1271:1275 arg1 length 1277:1282 cilia length 1271:1282 cilia length 1271:1282 Deletion of Ttc21b in juvenile ADPKD mice reduced cortical collecting duct cystogenesis and kidney weight/body weight ratios, increased proximal tubular and glomerular dilations, but did not reduce cilia length, inflammation, nor O-GlcNAc levels. 35644283 4 96 theme specific 550:557 arg1 components 565:574 specific cilia components 550:574 specific cilia components 550:574 These studies indicate that dysfunction of specific cilia components has potential therapeutic value. 35644283 0 97 theme autosomal 29:37 arg1 disease 66:72 autosomal dominant polycystic kidney disease 29:72 autosomal dominant polycystic kidney disease 29:72 Ttc21b deficiency attenuates autosomal dominant polycystic kidney disease in a kidney tubular- and maturation-dependent manner. 35644283 9 98 theme deletion 1511:1518 arg1 development-specific 1548:1567 development-specific 1548:1567 development-specific 1548:1567 Thus, unlike IFT-B, the effect of Ttc21b deletion in mouse models of ADPKD is development-specific. 35644283 9 98 theme deletion 1511:1518 arg1 effect 1494:1499 the effect 1490:1499 the effect of Ttc21b deletion in mouse models of ADPKD 1490:1543 Thus, unlike IFT-B, the effect of Ttc21b deletion in mouse models of ADPKD is development-specific. 35644283 4 99 theme components 565:574 arg1 dysfunction 535:545 dysfunction 535:545 dysfunction of specific cilia components 535:574 These studies indicate that dysfunction of specific cilia components has potential therapeutic value. 35644283 5 100 theme juvenile 762:769 arg1 models 787:792 juvenile and adult mouse models 762:792 juvenile and adult mouse models of ADPKD 762:801 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 9 101 theme mouse 1523:1527 arg1 models 1529:1534 mouse models 1523:1534 mouse models of ADPKD 1523:1543 Thus, unlike IFT-B, the effect of Ttc21b deletion in mouse models of ADPKD is development-specific. 35644283 8 102 theme Ttc21b 1333:1338 arg1 deletion 1340:1347 Ttc21b deletion 1333:1347 Ttc21b deletion in adult ADPKD mice 1333:1367 In contrast, Ttc21b deletion in adult ADPKD mice markedly attenuated kidney cystogenesis and reduced cilia length, inflammation, and O-GlcNAc levels. 35644283 5 103 theme gene 745:748 arg1 deletion 724:731 global deletion 717:731 global deletion of an IFT-A gene, Ttc21b, 717:757 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 5 104 theme adult 775:779 arg1 models 787:792 juvenile and adult mouse models 762:792 juvenile and adult mouse models of ADPKD 762:801 To broaden our understanding of cilia dysfunction and its therapeutic potential, we investigate the role of global deletion of an IFT-A gene, Ttc21b, in juvenile and adult mouse models of ADPKD. 35644283 6 105 theme ADPKD 867:871 arg1 mice 873:876 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice 804:876 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice 804:876 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 106 link O-linked 1030:1037 arg1 β-N-acetylglucosamine 1039:1059 O-linked β-N-acetylglucosamine 1030:1059 O-linked β-N-acetylglucosamine (O-GlcNAc) 1030:1070 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 106 link O-linked 1030:1037 arg1 O-GlcNAc 1062:1069 O-GlcNAc 1062:1069 O-GlcNAc 1062:1069 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 6 106 link O-linked 1030:1037 arg1 sensor 1022:1027 the nutrient sensor 1009:1027 the nutrient sensor 1009:1027 Both juvenile (postnatal day 21) and adult (six months of age) ADPKD mice exhibited kidney cysts, increased kidney weight/body weight ratios, lengthened kidney cilia, inflammation, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc). 35644283 3 107 theme adult 490:494 arg1 mice 496:499 adult mice 490:499 adult mice only 490:504 However, deletion of an IFT-A adaptor, Tulp3, attenuates PKD severity in adult mice only. 35644283 8 108 theme ADPKD 1358:1362 arg1 mice 1364:1367 adult ADPKD mice 1352:1367 adult ADPKD mice 1352:1367 In contrast, Ttc21b deletion in adult ADPKD mice markedly attenuated kidney cystogenesis and reduced cilia length, inflammation, and O-GlcNAc levels. 35644283 10 109 theme ADPKD 1623:1627 arg1 mice 1629:1632 juvenile ADPKD mice 1614:1632 juvenile ADPKD mice 1614:1632 Unlike an IFT-A adaptor, deleting Ttc21b in juvenile ADPKD mice is partially ameliorative. 35644283 2 110 theme mouse 403:407 arg1 models 409:414 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 35644283 2 111 theme disease 387:393 arg1 models 409:414 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models 331:414 Deletion of several IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult autosomal dominant polycystic kidney disease (ADPKD) mouse models. 36739885 8 0 with consistent 1079:1088 arg1 functions 1107:1115 the genetic functions 1095:1115 the genetic functions of SPY 1095:1122 Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. 36739885 0 1 from O-fucosylation 17:30 arg1 Arabidopsis 86:96 Arabidopsis 86:96 Arabidopsis 86:96 SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis. 36739885 3 2 gly O-fucosylated 455:467 arg1 proteins 446:453 the downstream substrate proteins 421:453 the downstream substrate proteins O-fucosylated by SPY 421:474 However, the upstream signal controlling SPY activity and the downstream substrate proteins O-fucosylated by SPY remain largely unknown. 36739885 8 3 theme developmental 1055:1067 arg1 programs 1069:1076 developmental programs 1055:1076 developmental programs 1055:1076 Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. 36739885 1 4 theme protein 147:153 arg1 O-fucosylation 155:168 SPINDLY (SPY)-catalyzed protein O-fucosylation 123:168 SPINDLY (SPY)-catalyzed protein O-fucosylation 123:168 The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. 36739885 9 5 theme many 1156:1159 arg1 proteins 1161:1168 many proteins 1156:1168 many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase 1156:1294 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 9 6 theme post-transcriptional/translational 1396:1429 arg1 regulation 1431:1440 post-transcriptional/translational regulation 1396:1440 post-transcriptional/translational regulation 1396:1440 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 4 7 from growth 556:561 arg1 thaliana 591:598 Arabidopsis (Arabidopsis thaliana) 566:599 Arabidopsis (Arabidopsis thaliana) 566:599 Here, we demonstrated that SPY mediates sugar-dependent growth in Arabidopsis (Arabidopsis thaliana). 36739885 5 8 theme proteins 650:657 arg1 hundreds 624:631 hundreds 624:631 hundreds of O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry 624:724 We further identified hundreds of O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry. 36739885 1 9 theme O-fucosylation 155:168 arg1 discovery 110:118 The recent discovery 99:118 The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation 99:168 The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. 36739885 10 10 theme nodes 1544:1548 arg1 targets 1500:1506 numerous targets 1491:1506 numerous targets of SPY/O-fucosylation and potential nodes of crosstalk 1491:1561 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 9 11 theme kinase 1289:1294 arg1 target 1263:1268 the target 1259:1268 the target of rapamycin (TOR) kinase 1259:1294 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 5 12 gly O-fucosylated 636:648 arg1 proteins 650:657 O-fucosylated proteins 636:657 O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry 636:724 We further identified hundreds of O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry. 36739885 9 13 theme phytohormone 1446:1457 arg1 responses 1459:1467 phytohormone responses 1446:1467 phytohormone responses 1446:1467 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 10 14 theme numerous 1491:1498 arg1 targets 1500:1506 numerous targets 1491:1506 numerous targets of SPY/O-fucosylation and potential nodes of crosstalk 1491:1561 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 5 15 theme lectin 665:670 arg1 chromatography 681:694 lectin affinity chromatography 665:694 lectin affinity chromatography followed by mass spectrometry 665:724 We further identified hundreds of O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry. 36739885 2 16 theme SPY 305:307 arg1 roles 296:300 important roles 286:300 important roles of SPY in diverse developmental and physiological processes 286:360 Genetic evidence indicates important roles of SPY in diverse developmental and physiological processes. 36739885 7 17 theme cytosolic 937:945 arg1 proteins 947:954 mostly nuclear and cytosolic proteins 918:954 mostly nuclear and cytosolic proteins 918:954 The O-fucosylome includes mostly nuclear and cytosolic proteins. 36739885 9 18 from convergence 1311:1321 arg1 regulation 1431:1440 post-transcriptional/translational regulation 1396:1440 post-transcriptional/translational regulation 1396:1440 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 9 18 from convergence 1311:1321 arg1 responses 1459:1467 phytohormone responses 1446:1467 phytohormone responses 1446:1467 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 9 18 from convergence 1311:1321 arg1 functions 1378:1386 key regulatory functions 1363:1386 key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses 1363:1467 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 8 19 theme Many 957:960 arg1 proteins 976:983 Many O-fucosylated proteins 957:983 Many O-fucosylated proteins 957:983 Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. 36739885 5 20 theme affinity 672:679 arg1 chromatography 681:694 lectin affinity chromatography 665:694 lectin affinity chromatography followed by mass spectrometry 665:724 We further identified hundreds of O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry. 36739885 3 21 theme substrate 436:444 arg1 proteins 446:453 the downstream substrate proteins 421:453 the downstream substrate proteins O-fucosylated by SPY 421:474 However, the upstream signal controlling SPY activity and the downstream substrate proteins O-fucosylated by SPY remain largely unknown. 36739885 10 22 theme growth 1696:1701 arg1 regulation 1676:1685 sugar regulation 1670:1685 sugar regulation of plant growth and development 1670:1717 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 10 23 theme network 1648:1654 arg1 dissection 1620:1629 future dissection 1613:1629 future dissection of the signaling network that mediates sugar regulation of plant growth and development 1613:1717 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 6 24 theme proteomic 775:783 arg1 analyses 785:792 our proteomic analyses 771:792 our proteomic analyses 771:792 All the O-fucosylation events quantified in our proteomic analyses were undetectable or dramatically decreased in the spy mutants, and thus likely catalyzed by SPY. 36739885 8 25 theme essential 997:1005 arg1 processes 1016:1024 essential cellular processes 997:1024 essential cellular processes 997:1024 Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. 36739885 10 26 gly SPY/O-fucosylation 1511:1528 arg1 crosstalk 1553:1561 crosstalk 1553:1561 crosstalk 1553:1561 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 10 27 theme signaling 1638:1646 arg1 network 1648:1654 the signaling network 1634:1654 the signaling network that mediates sugar regulation of plant growth and development 1634:1717 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 8 28 theme genetic 1099:1105 arg1 functions 1107:1115 the genetic functions 1095:1115 the genetic functions of SPY 1095:1122 Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. 36739885 2 29 theme physiological 338:350 arg1 processes 352:360 diverse developmental and physiological processes 312:360 diverse developmental and physiological processes 312:360 Genetic evidence indicates important roles of SPY in diverse developmental and physiological processes. 36739885 8 30 theme O-fucosylated 962:974 arg1 proteins 976:983 Many O-fucosylated proteins 957:983 Many O-fucosylated proteins 957:983 Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. 36739885 1 31 theme novel 181:185 arg1 mechanism 187:195 a novel mechanism 179:195 a novel mechanism for regulating nucleocytoplasmic protein functions in plants 179:256 The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. 36739885 10 32 theme sugar 1670:1674 arg1 regulation 1676:1685 sugar regulation 1670:1685 sugar regulation of plant growth and development 1670:1717 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 5 33 theme mass 708:711 arg1 spectrometry 713:724 mass spectrometry 708:724 mass spectrometry 708:724 We further identified hundreds of O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry. 36739885 8 34 theme SPY 1120:1122 arg1 functions 1107:1115 the genetic functions 1095:1115 the genetic functions of SPY 1095:1122 Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. 36739885 6 35 theme O-fucosylation 735:748 arg1 events 750:755 All the O-fucosylation events 727:755 All the O-fucosylation events quantified in our proteomic analyses 727:792 All the O-fucosylation events quantified in our proteomic analyses were undetectable or dramatically decreased in the spy mutants, and thus likely catalyzed by SPY. 36739885 3 36 theme SPY 404:406 arg1 activity 408:415 SPY activity 404:415 SPY activity 404:415 However, the upstream signal controlling SPY activity and the downstream substrate proteins O-fucosylated by SPY remain largely unknown. 36739885 10 37 theme signaling 1584:1592 arg1 pathways 1594:1601 sugar/nutrient signaling pathways 1569:1601 sugar/nutrient signaling pathways 1569:1601 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 10 38 theme future 1613:1618 arg1 dissection 1620:1629 future dissection 1613:1629 future dissection of the signaling network that mediates sugar regulation of plant growth and development 1613:1717 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 5 39 theme O-fucosylated 636:648 arg1 proteins 650:657 O-fucosylated proteins 636:657 O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry 636:724 We further identified hundreds of O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry. 36739885 2 40 theme developmental 320:332 arg1 processes 352:360 diverse developmental and physiological processes 312:360 diverse developmental and physiological processes 312:360 Genetic evidence indicates important roles of SPY in diverse developmental and physiological processes. 36739885 10 41 theme sugar/nutrient 1569:1582 arg1 pathways 1594:1601 sugar/nutrient signaling pathways 1569:1601 sugar/nutrient signaling pathways 1569:1601 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 9 42 theme nutrient 1332:1339 arg1 pathways 1351:1358 these nutrient signaling pathways 1326:1358 these nutrient signaling pathways 1326:1358 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 2 43 theme diverse 312:318 arg1 processes 352:360 diverse developmental and physiological processes 312:360 diverse developmental and physiological processes 312:360 Genetic evidence indicates important roles of SPY in diverse developmental and physiological processes. 36739885 8 44 theme cellular 1007:1014 arg1 processes 1016:1024 essential cellular processes 997:1024 essential cellular processes 997:1024 Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. 36739885 8 45 gly O-fucosylated 962:974 arg1 proteins 976:983 Many O-fucosylated proteins 957:983 Many O-fucosylated proteins 957:983 Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. 36739885 9 46 theme signaling 1341:1349 arg1 pathways 1351:1358 these nutrient signaling pathways 1326:1358 these nutrient signaling pathways 1326:1358 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 1 47 theme recent 103:108 arg1 discovery 110:118 The recent discovery 99:118 The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation 99:168 The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. 36739885 1 48 theme nucleocytoplasmic 212:228 arg1 functions 238:246 nucleocytoplasmic protein functions 212:246 nucleocytoplasmic protein functions in plants 212:256 The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. 36739885 0 49 theme hundreds 35:42 arg1 O-fucosylation 17:30 O-fucosylation 17:30 O-fucosylation of hundreds of proteins 17:54 SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis. 36739885 0 49 theme hundreds 35:42 arg1 growth 76:81 sugar-dependent growth 60:81 sugar-dependent growth in Arabidopsis 60:96 SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis. 36739885 3 50 theme O-fucosylated 455:467 arg1 proteins 446:453 the downstream substrate proteins 421:453 the downstream substrate proteins O-fucosylated by SPY 421:474 However, the upstream signal controlling SPY activity and the downstream substrate proteins O-fucosylated by SPY remain largely unknown. 36739885 0 51 from growth 76:81 arg1 Arabidopsis 86:96 Arabidopsis 86:96 Arabidopsis 86:96 SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis. 36739885 1 52 theme protein 230:236 arg1 functions 238:246 nucleocytoplasmic protein functions 212:246 nucleocytoplasmic protein functions in plants 212:256 The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. 36739885 3 53 theme downstream 425:434 arg1 proteins 446:453 the downstream substrate proteins 421:453 the downstream substrate proteins O-fucosylated by SPY 421:474 However, the upstream signal controlling SPY activity and the downstream substrate proteins O-fucosylated by SPY remain largely unknown. 36739885 4 54 theme Arabidopsis 566:576 arg1 thaliana 591:598 Arabidopsis (Arabidopsis thaliana) 566:599 Arabidopsis (Arabidopsis thaliana) 566:599 Here, we demonstrated that SPY mediates sugar-dependent growth in Arabidopsis (Arabidopsis thaliana). 36739885 10 55 theme development 1707:1717 arg1 regulation 1676:1685 sugar regulation 1670:1685 sugar regulation of plant growth and development 1670:1717 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 0 56 gly O-fucosylation 17:30 arg1 Arabidopsis 86:96 Arabidopsis 86:96 Arabidopsis 86:96 SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis. 36739885 0 56 gly O-fucosylation 17:30 arg1 hundreds 35:42 hundreds 35:42 hundreds of proteins 35:54 SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis. 36739885 6 57 theme spy 845:847 arg1 mutants 849:855 the spy mutants 841:855 the spy mutants 841:855 All the O-fucosylation events quantified in our proteomic analyses were undetectable or dramatically decreased in the spy mutants, and thus likely catalyzed by SPY. 36739885 0 58 theme proteins 47:54 arg1 hundreds 35:42 hundreds 35:42 hundreds of proteins 35:54 SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis. 36739885 10 59 theme crosstalk 1553:1561 arg1 SPY/O-fucosylation 1511:1528 SPY/O-fucosylation 1511:1528 SPY/O-fucosylation 1511:1528 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 10 59 theme crosstalk 1553:1561 arg1 nodes 1544:1548 potential nodes 1534:1548 potential nodes of crosstalk 1534:1561 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 3 60 theme upstream 376:383 arg1 signal 385:390 the upstream signal 372:390 the upstream signal controlling SPY activity 372:415 However, the upstream signal controlling SPY activity and the downstream substrate proteins O-fucosylated by SPY remain largely unknown. 36739885 9 61 theme key 1363:1365 arg1 regulation 1431:1440 post-transcriptional/translational regulation 1396:1440 post-transcriptional/translational regulation 1396:1440 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 9 61 theme key 1363:1365 arg1 responses 1459:1467 phytohormone responses 1446:1467 phytohormone responses 1446:1467 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 9 61 theme key 1363:1365 arg1 functions 1378:1386 key regulatory functions 1363:1386 key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses 1363:1467 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 9 62 theme pathways 1351:1358 arg1 convergence 1311:1321 the convergence 1307:1321 the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses 1307:1467 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 4 63 theme Arabidopsis 579:589 arg1 thaliana 591:598 Arabidopsis (Arabidopsis thaliana) 566:599 Arabidopsis (Arabidopsis thaliana) 566:599 Here, we demonstrated that SPY mediates sugar-dependent growth in Arabidopsis (Arabidopsis thaliana). 36739885 1 64 from functions 238:246 arg1 plants 251:256 plants 251:256 plants 251:256 The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. 36739885 9 65 theme regulatory 1367:1376 arg1 regulation 1431:1440 post-transcriptional/translational regulation 1396:1440 post-transcriptional/translational regulation 1396:1440 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 9 65 theme regulatory 1367:1376 arg1 responses 1459:1467 phytohormone responses 1446:1467 phytohormone responses 1446:1467 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 9 65 theme regulatory 1367:1376 arg1 functions 1378:1386 key regulatory functions 1363:1386 key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses 1363:1467 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 2 66 theme important 286:294 arg1 roles 296:300 important roles 286:300 important roles of SPY in diverse developmental and physiological processes 286:360 Genetic evidence indicates important roles of SPY in diverse developmental and physiological processes. 36739885 8 67 theme phytohormone 1027:1038 arg1 signaling 1040:1048 phytohormone signaling 1027:1048 phytohormone signaling 1027:1048 Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. 36739885 6 68 from mutants 849:855 arg1 undetectable 799:810 undetectable 799:810 undetectable 799:810 All the O-fucosylation events quantified in our proteomic analyses were undetectable or dramatically decreased in the spy mutants, and thus likely catalyzed by SPY. 36739885 2 69 from roles 296:300 arg1 processes 352:360 diverse developmental and physiological processes 312:360 diverse developmental and physiological processes 312:360 Genetic evidence indicates important roles of SPY in diverse developmental and physiological processes. 36739885 10 70 theme plant 1690:1694 arg1 growth 1696:1701 plant growth 1690:1701 plant growth 1690:1701 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 10 71 theme potential 1534:1542 arg1 nodes 1544:1548 potential nodes 1534:1548 potential nodes of crosstalk 1534:1561 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 6 72 from undetectable 799:810 arg1 mutants 849:855 the spy mutants 841:855 the spy mutants 841:855 All the O-fucosylation events quantified in our proteomic analyses were undetectable or dramatically decreased in the spy mutants, and thus likely catalyzed by SPY. 36739885 7 73 theme nuclear 925:931 arg1 proteins 947:954 mostly nuclear and cytosolic proteins 918:954 mostly nuclear and cytosolic proteins 918:954 The O-fucosylome includes mostly nuclear and cytosolic proteins. 36739885 9 74 theme rapamycin 1273:1281 arg1 kinase 1289:1294 rapamycin (TOR) kinase 1273:1294 rapamycin (TOR) kinase 1273:1294 The O-fucosylome also includes many proteins modified by O-linked-N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. 36739885 6 75 dep undetectable 799:810 arg1 catalyzed 874:882 catalyzed 874:882 catalyzed by SPY 874:889 All the O-fucosylation events quantified in our proteomic analyses were undetectable or dramatically decreased in the spy mutants, and thus likely catalyzed by SPY. 36739885 0 76 theme sugar-dependent 60:74 arg1 growth 76:81 sugar-dependent growth 60:81 sugar-dependent growth in Arabidopsis 60:96 SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis. 36739885 4 77 theme sugar-dependent 540:554 arg1 growth 556:561 sugar-dependent growth 540:561 sugar-dependent growth in Arabidopsis (Arabidopsis thaliana) 540:599 Here, we demonstrated that SPY mediates sugar-dependent growth in Arabidopsis (Arabidopsis thaliana). 36739885 2 78 theme Genetic 259:265 arg1 evidence 267:274 Genetic evidence 259:274 Genetic evidence 259:274 Genetic evidence indicates important roles of SPY in diverse developmental and physiological processes. 36739885 10 79 theme SPY/O-fucosylation 1511:1528 arg1 targets 1500:1506 numerous targets 1491:1506 numerous targets of SPY/O-fucosylation and potential nodes of crosstalk 1491:1561 Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development. 36739885 1 80 theme -catalyzed 136:145 arg1 O-fucosylation 155:168 SPINDLY (SPY)-catalyzed protein O-fucosylation 123:168 SPINDLY (SPY)-catalyzed protein O-fucosylation 123:168 The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. 36996108 1 0 theme compounds 253:261 arg1 diffusion 219:227 the diffusion 215:227 the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces 215:316 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 3 1 theme dimeric 708:714 arg1 configuration 742:754 a parallel dimeric alpha-helical coiled-coil configuration 697:754 a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds 697:791 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 1 2 theme small 267:271 arg1 proteins 273:280 small proteins 267:280 small proteins 267:280 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 4 3 theme sulfur-containing 870:886 arg1 residues 888:895 sulfur-containing residues 870:895 sulfur-containing residues (sulfur SAD) 870:908 The structure was solved using single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) to generate phase information. 36996108 4 3 theme sulfur-containing 870:886 arg1 SAD 905:907 sulfur SAD 898:907 sulfur SAD 898:907 The structure was solved using single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) to generate phase information. 36996108 6 4 theme PLVAP 1207:1211 arg1 ECD 1213:1215 the PLVAP ECD 1203:1215 the PLVAP ECD 1203:1215 Overall, ~2/3 of the ~390 amino acids within the PLVAP ECD adopt a helical configuration, as determined by CD. 36996108 9 5 theme N-linked 1794:1801 arg1 glycans 1803:1809 N-linked glycans 1794:1809 N-linked glycans 1794:1809 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 1 6 theme capillary 175:183 arg1 ECs 204:206 ECs 204:206 ECs 204:206 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 1 6 theme capillary 175:183 arg1 cells 197:201 capillary endothelial cells 175:201 capillary endothelial cells (ECs) 175:207 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 3 7 theme three-dimensional 569:585 arg1 structure 595:603 the three-dimensional crystal structure 565:603 the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) 565:671 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 6 8 theme amino 1184:1188 arg1 acids 1190:1194 the ~390 amino acids 1175:1194 the ~390 amino acids within the PLVAP ECD 1175:1215 Overall, ~2/3 of the ~390 amino acids within the PLVAP ECD adopt a helical configuration, as determined by CD. 36996108 3 9 theme coiled-coil 730:740 arg1 configuration 742:754 a parallel dimeric alpha-helical coiled-coil configuration 697:754 a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds 697:791 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 9 10 theme long 1706:1709 arg1 dimension 1711:1719 the long dimension 1702:1719 the long dimension of the pore-and 1702:1735 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 2 11 theme single-span 429:439 arg1 protein 463:469 a single-span type II transmembrane protein 427:469 a single-span type II transmembrane protein 427:469 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 2 11 theme single-span 429:439 arg1 protein-1 503:511 plasmalemma vesicle-associated protein-1 472:511 plasmalemma vesicle-associated protein-1 (PLVAP) 472:519 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 4 12 theme phase 922:926 arg1 information 928:938 phase information 922:938 phase information 922:938 The structure was solved using single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) to generate phase information. 36996108 3 13 theme interchain 766:775 arg1 bonds 787:791 five interchain disulfide bonds 761:791 five interchain disulfide bonds 761:791 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 5 14 theme alpha-helical 1058:1070 arg1 coil-held 1106:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held 1039:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds 1039:1155 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 9 15 theme pore-and 1728:1735 arg1 dimension 1711:1719 the long dimension 1702:1719 the long dimension of the pore-and 1702:1735 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 5 16 theme a 1097:1097 arg1 coil-held 1106:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held 1039:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds 1039:1155 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 5 17 theme dichroism 966:974 arg1 experiments 981:991 Biochemical and circular dichroism (CD) experiments 941:991 Biochemical and circular dichroism (CD) experiments 941:991 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 8 18 theme PLVAP 1487:1491 arg1 dimers 1493:1498 approximately ten PLVAP dimers 1469:1498 approximately ten PLVAP dimers 1469:1498 Taken together, these data lend strong support to the model of capillary diaphragms formulated by Tse and Stan in which approximately ten PLVAP dimers are arranged within each 60- to 80-nm-diameter opening like the spokes of a bicycle wheel. 36996108 6 19 theme helical 1225:1231 arg1 configuration 1233:1245 a helical configuration 1223:1245 a helical configuration 1223:1245 Overall, ~2/3 of the ~390 amino acids within the PLVAP ECD adopt a helical configuration, as determined by CD. 36996108 9 20 dep dimension 1711:1719 arg1 both 1668:1671 both 1668:1671 both 1668:1671 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 3 21 theme acid 620:623 arg1 segment 625:631 an 89-amino acid segment 608:631 an 89-amino acid segment of the PLVAP extracellular domain (ECD) 608:671 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 2 22 contain contain 334:340 arg1 openings 325:332 These openings 319:332 These openings 319:332 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 2 22 contain contain 334:340 arg2 diaphragm 344:352 a diaphragm 342:352 a diaphragm composed of radially arranged fibers 342:389 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 9 23 theme amino 1767:1771 arg1 chains 1783:1788 amino acid side chains 1767:1788 amino acid side chains 1767:1788 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 0 24 theme vascular 90:97 arg1 diaphragms 111:120 vascular endothelial diaphragms 90:120 vascular endothelial diaphragms 90:120 Structural insights into plasmalemma vesicle-associated protein (PLVAP): Implications for vascular endothelial diaphragms and fenestrae. 36996108 5 25 theme disulfide 1141:1149 arg1 bonds 1151:1155 interchain disulfide bonds 1130:1155 interchain disulfide bonds 1130:1155 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 7 26 dep sequence 1292:1299 arg1 the 1288:1290 the 1288:1290 the 1288:1290 We also determined the sequence and epitope of MECA-32, an anti-PLVAP antibody. 36996108 1 27 theme many 140:143 arg1 organs 145:150 many organs 140:150 many organs 140:150 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 9 28 theme side 1778:1781 arg1 chains 1783:1788 amino acid side chains 1767:1788 amino acid side chains 1767:1788 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 5 29 theme second 1005:1010 arg1 segment 1022:1028 a second PLVAP ECD segment 1003:1028 a second PLVAP ECD segment 1003:1028 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 2 30 theme II 446:447 arg1 protein 463:469 a single-span type II transmembrane protein 427:469 a single-span type II transmembrane protein 427:469 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 2 30 theme II 446:447 arg1 protein-1 503:511 plasmalemma vesicle-associated protein-1 472:511 plasmalemma vesicle-associated protein-1 (PLVAP) 472:519 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 8 31 theme 80-nm-diameter 1532:1545 arg1 opening 1547:1553 80-nm-diameter opening 1532:1553 80-nm-diameter opening 1532:1553 Taken together, these data lend strong support to the model of capillary diaphragms formulated by Tse and Stan in which approximately ten PLVAP dimers are arranged within each 60- to 80-nm-diameter opening like the spokes of a bicycle wheel. 36996108 8 32 theme strong 1381:1386 arg1 support 1388:1394 strong support 1381:1394 strong support 1381:1394 Taken together, these data lend strong support to the model of capillary diaphragms formulated by Tse and Stan in which approximately ten PLVAP dimers are arranged within each 60- to 80-nm-diameter opening like the spokes of a bicycle wheel. 36996108 0 33 theme Structural 0:9 arg1 insights 11:18 Structural insights 0:18 Structural insights into plasmalemma vesicle-associated protein (PLVAP): Implications for vascular endothelial diaphragms and fenestrae. 0:135 Structural insights into plasmalemma vesicle-associated protein (PLVAP): Implications for vascular endothelial diaphragms and fenestrae. 36996108 1 34 theme proteins 273:280 arg1 diffusion 219:227 the diffusion 215:227 the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces 215:316 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 9 35 theme glycans 1803:1809 arg1 properties 1753:1762 the chemical properties 1740:1762 the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP 1740:1850 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 2 36 theme plasmalemma 472:482 arg1 protein 463:469 a single-span type II transmembrane protein 427:469 a single-span type II transmembrane protein 427:469 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 2 36 theme plasmalemma 472:482 arg1 PLVAP 514:518 PLVAP 514:518 PLVAP 514:518 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 2 36 theme plasmalemma 472:482 arg1 protein-1 503:511 plasmalemma vesicle-associated protein-1 472:511 plasmalemma vesicle-associated protein-1 (PLVAP) 472:519 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 3 37 theme domain 660:665 arg1 segment 625:631 an 89-amino acid segment 608:631 an 89-amino acid segment of the PLVAP extracellular domain (ECD) 608:671 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 4 38 theme single-wavelength 825:841 arg1 diffraction 853:863 single-wavelength anomalous diffraction 825:863 single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) 825:908 The structure was solved using single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) to generate phase information. 36996108 0 39 theme vesicle-associated 37:54 arg1 protein 56:62 plasmalemma vesicle-associated protein 25:62 plasmalemma vesicle-associated protein (PLVAP) 25:70 Structural insights into plasmalemma vesicle-associated protein (PLVAP): Implications for vascular endothelial diaphragms and fenestrae. 36996108 0 39 theme vesicle-associated 37:54 arg1 PLVAP 65:69 PLVAP 65:69 PLVAP 65:69 Structural insights into plasmalemma vesicle-associated protein (PLVAP): Implications for vascular endothelial diaphragms and fenestrae. 36996108 7 40 theme MECA-32 1316:1322 arg1 sequence 1292:1299 sequence 1292:1299 sequence 1292:1299 We also determined the sequence and epitope of MECA-32, an anti-PLVAP antibody. 36996108 7 40 theme MECA-32 1316:1322 arg1 epitope 1305:1311 epitope 1305:1311 epitope 1305:1311 We also determined the sequence and epitope of MECA-32, an anti-PLVAP antibody. 36996108 3 41 theme PLVAP 640:644 arg1 ECD 668:670 ECD 668:670 ECD 668:670 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 3 41 theme PLVAP 640:644 arg1 domain 660:665 PLVAP extracellular domain 640:665 the PLVAP extracellular domain (ECD) 636:671 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 8 42 theme capillary 1412:1420 arg1 diaphragms 1422:1431 capillary diaphragms 1412:1431 capillary diaphragms formulated by Tse and Stan 1412:1458 Taken together, these data lend strong support to the model of capillary diaphragms formulated by Tse and Stan in which approximately ten PLVAP dimers are arranged within each 60- to 80-nm-diameter opening like the spokes of a bicycle wheel. 36996108 9 43 from properties 1753:1762 arg1 faces 1837:1841 the solvent-accessible faces 1814:1841 the solvent-accessible faces of PLVAP 1814:1850 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 5 44 theme dimeric 1050:1056 arg1 coil-held 1106:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held 1039:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds 1039:1155 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 9 45 theme PLVAP 1846:1850 arg1 faces 1837:1841 the solvent-accessible faces 1814:1841 the solvent-accessible faces of PLVAP 1814:1850 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 8 46 theme wheel 1584:1588 arg1 spokes 1564:1569 the spokes 1560:1569 the spokes of a bicycle wheel 1560:1588 Taken together, these data lend strong support to the model of capillary diaphragms formulated by Tse and Stan in which approximately ten PLVAP dimers are arranged within each 60- to 80-nm-diameter opening like the spokes of a bicycle wheel. 36996108 5 47 theme ECD 1018:1020 arg1 segment 1022:1028 a second PLVAP ECD segment 1003:1028 a second PLVAP ECD segment 1003:1028 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 9 48 from faces 1837:1841 arg1 properties 1753:1762 the chemical properties 1740:1762 the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP 1740:1850 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 1 49 theme weight 246:251 arg1 compounds 253:261 low-molecular weight compounds 232:261 low-molecular weight compounds 232:261 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 9 50 theme molecules 1602:1610 arg1 Passage 1591:1597 Passage 1591:1597 Passage of molecules through the wedge-shaped pores 1591:1641 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 9 51 from glycans 1803:1809 arg1 faces 1837:1841 the solvent-accessible faces 1814:1841 the solvent-accessible faces of PLVAP 1814:1850 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 3 52 theme alpha-helical 716:728 arg1 configuration 742:754 a parallel dimeric alpha-helical coiled-coil configuration 697:754 a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds 697:791 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 3 53 theme parallel 699:706 arg1 configuration 742:754 a parallel dimeric alpha-helical coiled-coil configuration 697:754 a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds 697:791 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 1 54 theme endothelial 185:195 arg1 ECs 204:206 ECs 204:206 ECs 204:206 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 1 54 theme endothelial 185:195 arg1 cells 197:201 capillary endothelial cells 175:201 capillary endothelial cells (ECs) 175:207 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 9 55 theme PLVAP-i.e. 1690:1699 arg1 length 1680:1685 the length 1676:1685 the length of PLVAP-i.e. 1676:1699 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 6 56 theme acids 1190:1194 arg1 ~2/3 1167:1170 ~2/3 1167:1170 ~2/3 of the ~390 amino acids within the PLVAP ECD 1167:1215 Overall, ~2/3 of the ~390 amino acids within the PLVAP ECD adopt a helical configuration, as determined by CD. 36996108 5 57 theme interchain 1130:1139 arg1 bonds 1151:1155 interchain disulfide bonds 1130:1155 interchain disulfide bonds 1130:1155 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 3 58 theme crystal 587:593 arg1 structure 595:603 the three-dimensional crystal structure 565:603 the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) 565:671 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 5 59 theme Biochemical 941:951 arg1 experiments 981:991 Biochemical and circular dichroism (CD) experiments 941:991 Biochemical and circular dichroism (CD) experiments 941:991 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 3 60 theme disulfide 777:785 arg1 bonds 787:791 five interchain disulfide bonds 761:791 five interchain disulfide bonds 761:791 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 5 61 theme configuration-presumably 1072:1095 arg1 coil-held 1106:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held 1039:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds 1039:1155 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 3 62 theme segment 625:631 arg1 structure 595:603 the three-dimensional crystal structure 565:603 the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) 565:671 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 5 63 theme circular 957:964 arg1 CD 977:978 CD 977:978 CD 977:978 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 5 63 theme circular 957:964 arg1 dichroism 966:974 circular dichroism 957:974 circular dichroism (CD) 957:979 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 6 64 dep configuration 1233:1245 arg1 determined 1251:1260 determined 1251:1260 determined by CD 1251:1266 Overall, ~2/3 of the ~390 amino acids within the PLVAP ECD adopt a helical configuration, as determined by CD. 36996108 5 65 theme coiled 1099:1104 arg1 coil-held 1106:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held 1039:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds 1039:1155 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 3 66 theme 89-amino 611:618 arg1 segment 625:631 an 89-amino acid segment 608:631 an 89-amino acid segment of the PLVAP extracellular domain (ECD) 608:671 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 9 67 theme chemical 1744:1751 arg1 properties 1753:1762 the chemical properties 1740:1762 the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP 1740:1850 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 9 68 link N-linked 1794:1801 arg1 glycans 1803:1809 N-linked glycans 1794:1809 N-linked glycans 1794:1809 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 1 69 theme small 153:157 arg1 openings 159:166 small openings 153:166 small openings across capillary endothelial cells (ECs) 153:207 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 2 70 theme vesicle-associated 484:501 arg1 protein 463:469 a single-span type II transmembrane protein 427:469 a single-span type II transmembrane protein 427:469 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 2 70 theme vesicle-associated 484:501 arg1 PLVAP 514:518 PLVAP 514:518 PLVAP 514:518 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 2 70 theme vesicle-associated 484:501 arg1 protein-1 503:511 plasmalemma vesicle-associated protein-1 472:511 plasmalemma vesicle-associated protein-1 (PLVAP) 472:519 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 0 71 theme endothelial 99:109 arg1 diaphragms 111:120 vascular endothelial diaphragms 90:120 vascular endothelial diaphragms 90:120 Structural insights into plasmalemma vesicle-associated protein (PLVAP): Implications for vascular endothelial diaphragms and fenestrae. 36996108 9 72 theme wedge-shaped 1624:1635 arg1 pores 1637:1641 the wedge-shaped pores 1620:1641 the wedge-shaped pores 1620:1641 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 9 73 theme acid 1773:1776 arg1 chains 1783:1788 amino acid side chains 1767:1788 amino acid side chains 1767:1788 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 4 74 from residues 888:895 arg1 diffraction 853:863 single-wavelength anomalous diffraction 825:863 single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) 825:908 The structure was solved using single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) to generate phase information. 36996108 9 75 theme chains 1783:1788 arg1 properties 1753:1762 the chemical properties 1740:1762 the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP 1740:1850 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 3 76 with configuration 742:754 arg1 bonds 787:791 five interchain disulfide bonds 761:791 five interchain disulfide bonds 761:791 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 7 77 theme anti-PLVAP 1328:1337 arg1 antibody 1339:1346 an anti-PLVAP antibody 1325:1346 an anti-PLVAP antibody 1325:1346 We also determined the sequence and epitope of MECA-32, an anti-PLVAP antibody. 36996108 7 77 theme anti-PLVAP 1328:1337 arg1 MECA-32 1316:1322 MECA-32 1316:1322 MECA-32 1316:1322 We also determined the sequence and epitope of MECA-32, an anti-PLVAP antibody. 36996108 2 78 theme type 441:444 arg1 protein 463:469 a single-span type II transmembrane protein 427:469 a single-span type II transmembrane protein 427:469 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 2 78 theme type 441:444 arg1 protein-1 503:511 plasmalemma vesicle-associated protein-1 472:511 plasmalemma vesicle-associated protein-1 (PLVAP) 472:519 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 2 79 theme arranged 375:382 arg1 fibers 384:389 radially arranged fibers 366:389 radially arranged fibers 366:389 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 0 80 theme plasmalemma 25:35 arg1 protein 56:62 plasmalemma vesicle-associated protein 25:62 plasmalemma vesicle-associated protein (PLVAP) 25:70 Structural insights into plasmalemma vesicle-associated protein (PLVAP): Implications for vascular endothelial diaphragms and fenestrae. 36996108 0 80 theme plasmalemma 25:35 arg1 PLVAP 65:69 PLVAP 65:69 PLVAP 65:69 Structural insights into plasmalemma vesicle-associated protein (PLVAP): Implications for vascular endothelial diaphragms and fenestrae. 36996108 3 81 theme extracellular 646:658 arg1 ECD 668:670 ECD 668:670 ECD 668:670 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 3 81 theme extracellular 646:658 arg1 domain 660:665 PLVAP extracellular domain 640:665 the PLVAP extracellular domain (ECD) 636:671 Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. 36996108 1 82 theme blood 294:298 arg1 spaces 311:316 the blood and tissue spaces 290:316 spaces 311:316 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 9 83 from chains 1783:1788 arg1 faces 1837:1841 the solvent-accessible faces 1814:1841 the solvent-accessible faces of PLVAP 1814:1850 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 9 84 theme solvent-accessible 1818:1835 arg1 faces 1837:1841 the solvent-accessible faces 1814:1841 the solvent-accessible faces of PLVAP 1814:1850 Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP. 36996108 8 85 theme bicycle 1576:1582 arg1 wheel 1584:1588 a bicycle wheel 1574:1588 a bicycle wheel 1574:1588 Taken together, these data lend strong support to the model of capillary diaphragms formulated by Tse and Stan in which approximately ten PLVAP dimers are arranged within each 60- to 80-nm-diameter opening like the spokes of a bicycle wheel. 36996108 2 86 theme current 396:402 arg1 evidence 404:411 current evidence 396:411 current evidence 396:411 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 1 87 theme tissue 304:309 arg1 spaces 311:316 the blood and tissue spaces 290:316 spaces 311:316 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36996108 5 88 theme parallel 1041:1048 arg1 coil-held 1106:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held 1039:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds 1039:1155 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 2 89 theme transmembrane 449:461 arg1 protein 463:469 a single-span type II transmembrane protein 427:469 a single-span type II transmembrane protein 427:469 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 2 89 theme transmembrane 449:461 arg1 protein-1 503:511 plasmalemma vesicle-associated protein-1 472:511 plasmalemma vesicle-associated protein-1 (PLVAP) 472:519 These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. 36996108 4 90 theme anomalous 843:851 arg1 diffraction 853:863 single-wavelength anomalous diffraction 825:863 single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) 825:908 The structure was solved using single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) to generate phase information. 36996108 5 91 theme PLVAP 1012:1016 arg1 segment 1022:1028 a second PLVAP ECD segment 1003:1028 a second PLVAP ECD segment 1003:1028 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 8 92 theme diaphragms 1422:1431 arg1 model 1403:1407 the model 1399:1407 the model of capillary diaphragms formulated by Tse and Stan in which approximately ten PLVAP dimers are arranged within each 60- to 80-nm-diameter opening like the spokes of a bicycle wheel 1399:1588 Taken together, these data lend strong support to the model of capillary diaphragms formulated by Tse and Stan in which approximately ten PLVAP dimers are arranged within each 60- to 80-nm-diameter opening like the spokes of a bicycle wheel. 36996108 0 93 dep insights 11:18 arg1 Implications 73:84 Implications 73:84 Structural insights into plasmalemma vesicle-associated protein (PLVAP): Implications for vascular endothelial diaphragms and fenestrae. 0:135 Structural insights into plasmalemma vesicle-associated protein (PLVAP): Implications for vascular endothelial diaphragms and fenestrae. 36996108 5 94 contain has 1035:1037 arg1 segment 1022:1028 a second PLVAP ECD segment 1003:1028 a second PLVAP ECD segment 1003:1028 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 5 94 contain has 1035:1037 arg2 coil-held 1106:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held 1039:1114 a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds 1039:1155 Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. 36996108 1 95 theme low-molecular 232:244 arg1 compounds 253:261 low-molecular weight compounds 232:261 low-molecular weight compounds 232:261 In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. 36879070 1 0 theme patients 221:228 arg1 % 207:207 for ~ 15% 199:207 for ~ 15% of Japanese patients with genetic prion diseases 199:256 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 1 0 theme patients 221:228 arg1 patients 221:228 Japanese patients 212:228 Japanese patients with genetic prion diseases 212:256 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 10 1 theme signal 1819:1824 arg1 peptide 1826:1832 the GPI-attachment signal peptide 1800:1832 the GPI-attachment signal peptide 1800:1832 To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease. 36879070 1 2 theme genetic 235:241 arg1 diseases 249:256 genetic prion diseases 235:256 genetic prion diseases 235:256 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 3 3 from addition 436:443 arg1 indistinguishable 506:522 indistinguishable 506:522 indistinguishable 506:522 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 3 3 from addition 436:443 arg1 phenotypes 468:477 the clinicopathologic phenotypes 446:477 the clinicopathologic phenotypes of patients with M232R 446:500 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 10 4 theme direct 1752:1757 arg1 relationship 1759:1770 a direct relationship 1750:1770 a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease 1750:1863 To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease. 36879070 3 5 theme Creutzfeldt-Jakob 547:563 arg1 patients 573:580 sporadic Creutzfeldt-Jakob disease patients 538:580 sporadic Creutzfeldt-Jakob disease patients 538:580 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 9 6 theme reticulum 1476:1484 arg1 pathway 1500:1506 endoplasmic reticulum translocation pathway 1464:1506 endoplasmic reticulum translocation pathway of prion proteins 1464:1524 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 6 7 theme GPI-attachment 946:959 arg1 peptide 968:974 the GPI-attachment signal peptide 942:974 the GPI-attachment signal peptide of prion protein 942:991 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 10 8 theme point 1782:1786 arg1 mutation 1788:1795 a point mutation 1780:1795 a point mutation in the GPI-attachment signal peptide 1780:1832 To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease. 36879070 4 9 from located 622:628 arg1 peptide 690:696 the glycosylphosphatidylinositol (GPI)-attachment signal peptide 633:696 the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins 633:756 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 1 10 theme prion 171:175 arg1 gene 185:188 the prion protein gene 167:188 the prion protein gene 167:188 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 9 11 theme prion 1511:1515 arg1 proteins 1517:1524 prion proteins 1511:1524 prion proteins 1511:1524 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 9 12 link N-linked 1625:1632 arg1 glycosylation 1634:1646 N-linked glycosylation 1625:1646 N-linked glycosylation 1625:1646 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 6 13 theme M232R 920:924 arg1 substitution 926:937 the M232R substitution 916:937 the M232R substitution 916:937 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 10 14 theme GPI-attachment 1804:1817 arg1 peptide 1826:1832 the GPI-attachment signal peptide 1800:1832 the GPI-attachment signal peptide 1800:1832 To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease. 36879070 2 15 with patients 412:419 arg1 M232R 426:430 M232R 426:430 M232R 426:430 However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. 36879070 4 16 located located 622:628 arg1 peptide 690:696 the glycosylphosphatidylinositol (GPI)-attachment signal peptide 633:696 the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins 633:756 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 4 16 located located 622:628 arg2 substitution 606:617 the M232R substitution 596:617 the M232R substitution 596:617 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 4 16 located located 622:628 arg2 located 622:628 located 622:628 located 622:628 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 4 17 theme signal 683:688 arg1 peptide 690:696 the glycosylphosphatidylinositol (GPI)-attachment signal peptide 633:696 the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins 633:756 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 7 18 theme disease 1220:1226 arg1 development 1199:1209 the development 1195:1209 the development of prion disease 1195:1226 The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. 36879070 5 19 theme pathogenic 873:882 arg1 mutation 884:891 a pathogenic mutation 871:891 an uncommon polymorphism rather than a pathogenic mutation 834:891 Therefore, there has been an argument that the M232R substitution might be an uncommon polymorphism rather than a pathogenic mutation. 36879070 10 20 from mutation 1788:1795 arg1 peptide 1826:1832 the GPI-attachment signal peptide 1800:1832 the GPI-attachment signal peptide 1800:1832 To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease. 36879070 0 21 from mutation 8:15 arg1 peptide 42:48 GPI-attachment signal peptide 20:48 GPI-attachment signal peptide 20:48 A point mutation in GPI-attachment signal peptide accelerates the development of prion disease. 36879070 1 22 from codon 146:150 arg1 arginine 134:141 arginine 134:141 arginine at codon 232 134:154 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 9 23 theme GPI-attachment 1564:1577 arg1 peptide 1586:1592 the GPI-attachment signal peptide 1560:1592 the GPI-attachment signal peptide 1560:1592 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 6 24 theme prion 979:983 arg1 protein 985:991 prion protein 979:991 prion protein 979:991 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 0 25 theme disease 87:93 arg1 development 66:76 the development 62:76 the development of prion disease 62:93 A point mutation in GPI-attachment signal peptide accelerates the development of prion disease. 36879070 9 26 theme peptide 1586:1592 arg1 hydrophobicity 1542:1555 the hydrophobicity 1538:1555 the hydrophobicity of the GPI-attachment signal peptide 1538:1592 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 1 27 from methionine 120:129 arg1 variant 107:113 A missense variant 96:113 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene 96:188 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 1 27 from methionine 120:129 arg1 M232R 157:161 M232R 157:161 M232R 157:161 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 1 28 theme prion 243:247 arg1 diseases 249:256 genetic prion diseases 235:256 genetic prion diseases 235:256 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 10 29 from development 1842:1852 arg1 peptide 1826:1832 the GPI-attachment signal peptide 1800:1832 the GPI-attachment signal peptide 1800:1832 To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease. 36879070 4 30 theme prion 743:747 arg1 proteins 749:756 prion proteins 743:756 prion proteins 743:756 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 5 31 theme M232R 806:810 arg1 polymorphism 846:857 an uncommon polymorphism 834:857 an uncommon polymorphism rather than a pathogenic mutation 834:891 Therefore, there has been an argument that the M232R substitution might be an uncommon polymorphism rather than a pathogenic mutation. 36879070 5 31 theme M232R 806:810 arg1 substitution 812:823 the M232R substitution 802:823 the M232R substitution 802:823 Therefore, there has been an argument that the M232R substitution might be an uncommon polymorphism rather than a pathogenic mutation. 36879070 1 32 theme missense 98:105 arg1 variant 107:113 A missense variant 96:113 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene 96:188 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 1 32 theme missense 98:105 arg1 M232R 157:161 M232R 157:161 M232R 157:161 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 7 33 theme prion 1282:1286 arg1 features 1336:1343 prion strain-specific histopathologic and biochemical features 1282:1343 prion strain-specific histopathologic and biochemical features 1282:1343 The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. 36879070 2 34 theme family 376:381 arg1 history 383:389 family history 376:389 family history 376:389 However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. 36879070 0 35 theme GPI-attachment 20:33 arg1 peptide 42:48 GPI-attachment signal peptide 20:48 GPI-attachment signal peptide 20:48 A point mutation in GPI-attachment signal peptide accelerates the development of prion disease. 36879070 9 36 theme glycosylation 1634:1646 arg1 reduction 1612:1620 the reduction 1608:1620 the reduction of N-linked glycosylation 1608:1646 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 9 36 theme glycosylation 1634:1646 arg1 glycosylation 1656:1668 GPI glycosylation 1652:1668 GPI glycosylation of prion proteins 1652:1686 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 7 37 theme strain-specific 1288:1302 arg1 features 1336:1343 prion strain-specific histopathologic and biochemical features 1282:1343 prion strain-specific histopathologic and biochemical features 1282:1343 The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. 36879070 8 38 theme site 1424:1427 arg1 attachment 1387:1396 the attachment 1383:1396 the attachment of GPI nor GPI-attachment site 1383:1427 The M232R substitution did not alter the attachment of GPI nor GPI-attachment site. 36879070 10 39 theme first 1731:1735 arg1 this 1719:1722 this 1719:1722 this 1719:1722 To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease. 36879070 10 39 theme first 1731:1735 arg1 time 1737:1740 the first time 1727:1740 the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease 1727:1863 To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease. 36879070 9 40 theme GPI 1652:1654 arg1 glycosylation 1656:1668 GPI glycosylation 1652:1668 GPI glycosylation of prion proteins 1652:1686 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 2 41 theme M232R 292:296 arg1 substitution 298:309 the M232R substitution 288:309 the M232R substitution 288:309 However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. 36879070 6 42 theme prion 1016:1020 arg1 disease 1022:1028 prion disease 1016:1028 prion disease 1016:1028 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 3 43 theme patients 482:489 arg1 indistinguishable 506:522 indistinguishable 506:522 indistinguishable 506:522 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 3 43 theme patients 482:489 arg1 phenotypes 468:477 the clinicopathologic phenotypes 446:477 the clinicopathologic phenotypes of patients with M232R 446:500 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 9 44 theme proteins 1679:1686 arg1 reduction 1612:1620 the reduction 1608:1620 the reduction of N-linked glycosylation 1608:1646 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 9 44 theme proteins 1679:1686 arg1 glycosylation 1656:1668 GPI glycosylation 1652:1668 GPI glycosylation of prion proteins 1652:1686 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 6 45 theme human 1074:1078 arg1 proteins 1086:1093 human prion proteins 1074:1093 human prion proteins 1074:1093 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 4 46 theme M232R 600:604 arg1 located 622:628 located 622:628 located 622:628 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 4 46 theme M232R 600:604 arg1 substitution 606:617 the M232R substitution 596:617 the M232R substitution 596:617 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 6 47 from role 908:911 arg1 peptide 968:974 the GPI-attachment signal peptide 942:974 the GPI-attachment signal peptide of prion protein 942:991 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 4 48 from peptide 690:696 arg1 located 622:628 located 622:628 located 622:628 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 4 48 from peptide 690:696 arg1 substitution 606:617 the M232R substitution 596:617 the M232R substitution 596:617 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 1 49 theme Japanese 212:219 arg1 patients 221:228 Japanese patients 212:228 Japanese patients with genetic prion diseases 212:256 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 9 50 gly glycosylation 1656:1668 arg1 glycosylation 1634:1646 N-linked glycosylation 1625:1646 N-linked glycosylation 1625:1646 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 9 50 gly glycosylation 1656:1668 arg1 proteins 1679:1686 prion proteins 1673:1686 prion proteins 1673:1686 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 3 51 with patients 482:489 arg1 M232R 496:500 M232R 496:500 M232R 496:500 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 5 52 theme uncommon 837:844 arg1 polymorphism 846:857 an uncommon polymorphism 834:857 an uncommon polymorphism rather than a pathogenic mutation 834:891 Therefore, there has been an argument that the M232R substitution might be an uncommon polymorphism rather than a pathogenic mutation. 36879070 5 52 theme uncommon 837:844 arg1 substitution 812:823 the M232R substitution 802:823 the M232R substitution 802:823 Therefore, there has been an argument that the M232R substitution might be an uncommon polymorphism rather than a pathogenic mutation. 36879070 6 53 theme prion 1145:1149 arg1 disease 1151:1157 prion disease 1145:1157 prion disease 1145:1157 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 3 54 theme sporadic 538:545 arg1 patients 573:580 sporadic Creutzfeldt-Jakob disease patients 538:580 sporadic Creutzfeldt-Jakob disease patients 538:580 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 9 55 theme endoplasmic 1464:1474 arg1 reticulum 1476:1484 endoplasmic reticulum 1464:1484 endoplasmic reticulum translocation pathway of prion proteins 1464:1524 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 6 56 theme signal 961:966 arg1 peptide 968:974 the GPI-attachment signal peptide 942:974 the GPI-attachment signal peptide of prion protein 942:991 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 2 57 theme pathogenic 268:277 arg1 roles 279:283 pathogenic roles 268:283 pathogenic roles of the M232R substitution for the induction of prion disease 268:344 However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. 36879070 9 58 theme translocation 1486:1498 arg1 pathway 1500:1506 endoplasmic reticulum translocation pathway 1464:1506 endoplasmic reticulum translocation pathway of prion proteins 1464:1524 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 2 59 theme prion 332:336 arg1 disease 338:344 prion disease 332:344 prion disease 332:344 However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. 36879070 2 60 theme substitution 298:309 arg1 roles 279:283 pathogenic roles 268:283 pathogenic roles of the M232R substitution for the induction of prion disease 268:344 However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. 36879070 1 61 theme protein 177:183 arg1 gene 185:188 the prion protein gene 167:188 the prion protein gene 167:188 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 6 62 theme substitution 926:937 arg1 role 908:911 the role 904:911 the role of the M232R substitution in the GPI-attachment signal peptide of prion protein 904:991 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 3 63 theme disease 565:571 arg1 patients 573:580 sporadic Creutzfeldt-Jakob disease patients 538:580 sporadic Creutzfeldt-Jakob disease patients 538:580 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 9 64 theme proteins 1517:1524 arg1 pathway 1500:1506 endoplasmic reticulum translocation pathway 1464:1506 endoplasmic reticulum translocation pathway of prion proteins 1464:1524 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 3 65 from those 529:533 arg1 indistinguishable 506:522 indistinguishable 506:522 indistinguishable 506:522 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 3 65 from those 529:533 arg1 phenotypes 468:477 the clinicopathologic phenotypes 446:477 the clinicopathologic phenotypes of patients with M232R 446:500 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 10 66 theme disease 1857:1863 arg1 mutation 1788:1795 a point mutation 1780:1795 a point mutation in the GPI-attachment signal peptide 1780:1832 To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease. 36879070 10 66 theme disease 1857:1863 arg1 development 1842:1852 the development 1838:1852 the development of disease 1838:1863 To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease. 36879070 7 67 theme prion 1214:1218 arg1 disease 1220:1226 prion disease 1214:1226 prion disease 1214:1226 The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. 36879070 2 68 from absent 402:407 arg1 patients 412:419 patients 412:419 patients with M232R 412:430 However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. 36879070 4 69 theme -attachment 671:681 arg1 peptide 690:696 the glycosylphosphatidylinositol (GPI)-attachment signal peptide 633:696 the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins 633:756 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 0 70 theme prion 81:85 arg1 disease 87:93 prion disease 81:93 prion disease 81:93 A point mutation in GPI-attachment signal peptide accelerates the development of prion disease. 36879070 6 71 theme protein 985:991 arg1 peptide 968:974 the GPI-attachment signal peptide 942:974 the GPI-attachment signal peptide of prion protein 942:991 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 2 72 from patients 412:419 arg1 absent 402:407 absent 402:407 absent 402:407 However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. 36879070 3 73 from indistinguishable 506:522 arg1 addition 436:443 addition 436:443 addition 436:443 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 9 74 theme signal 1579:1584 arg1 peptide 1586:1592 the GPI-attachment signal peptide 1560:1592 the GPI-attachment signal peptide 1560:1592 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 8 75 theme M232R 1350:1354 arg1 substitution 1356:1367 The M232R substitution 1346:1367 The M232R substitution 1346:1367 The M232R substitution did not alter the attachment of GPI nor GPI-attachment site. 36879070 4 76 theme proteins 749:756 arg1 maturation 729:738 the maturation 725:738 the maturation of prion proteins 725:756 Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. 36879070 7 77 theme M232R 1164:1168 arg1 substitution 1170:1181 The M232R substitution 1160:1181 The M232R substitution 1160:1181 The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. 36879070 6 78 theme mouse 1051:1055 arg1 model 1057:1061 a mouse model 1049:1061 a mouse model 1049:1061 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 0 79 theme point 2:6 arg1 mutation 8:15 A point mutation 0:15 A point mutation in GPI-attachment signal peptide 0:48 A point mutation in GPI-attachment signal peptide accelerates the development of prion disease. 36879070 7 80 theme biochemical 1324:1334 arg1 features 1336:1343 prion strain-specific histopathologic and biochemical features 1282:1343 prion strain-specific histopathologic and biochemical features 1282:1343 The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. 36879070 2 81 theme disease 338:344 arg1 induction 319:327 the induction 315:327 the induction of prion disease 315:344 However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. 36879070 7 82 theme histopathologic 1304:1318 arg1 features 1336:1343 prion strain-specific histopathologic and biochemical features 1282:1343 prion strain-specific histopathologic and biochemical features 1282:1343 The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. 36879070 6 83 theme prion 1080:1084 arg1 proteins 1086:1093 human prion proteins 1074:1093 human prion proteins 1074:1093 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 0 84 theme signal 35:40 arg1 peptide 42:48 GPI-attachment signal peptide 20:48 GPI-attachment signal peptide 20:48 A point mutation in GPI-attachment signal peptide accelerates the development of prion disease. 36879070 9 85 theme N-linked 1625:1632 arg1 glycosylation 1634:1646 N-linked glycosylation 1625:1646 N-linked glycosylation 1625:1646 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 6 86 theme disease 1022:1028 arg1 pathogenesis 1000:1011 the pathogenesis 996:1011 the pathogenesis of prion disease 996:1028 To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. 36879070 8 87 theme GPI 1401:1403 arg1 attachment 1387:1396 the attachment 1383:1396 the attachment of GPI nor GPI-attachment site 1383:1427 The M232R substitution did not alter the attachment of GPI nor GPI-attachment site. 36879070 8 88 theme GPI-attachment 1409:1422 arg1 site 1424:1427 GPI-attachment site 1409:1427 GPI-attachment site 1409:1427 The M232R substitution did not alter the attachment of GPI nor GPI-attachment site. 36879070 3 89 theme clinicopathologic 450:466 arg1 indistinguishable 506:522 indistinguishable 506:522 indistinguishable 506:522 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 3 89 theme clinicopathologic 450:466 arg1 phenotypes 468:477 the clinicopathologic phenotypes 446:477 the clinicopathologic phenotypes of patients with M232R 446:500 In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. 36879070 1 90 with patients 221:228 arg1 diseases 249:256 genetic prion diseases 235:256 genetic prion diseases 235:256 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 7 91 theme strain-dependent 1239:1254 arg1 manner 1256:1261 a prion strain-dependent manner 1231:1261 a prion strain-dependent manner 1231:1261 The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. 36879070 1 92 theme gene 185:188 arg1 variant 107:113 A missense variant 96:113 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene 96:188 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 1 92 theme gene 185:188 arg1 M232R 157:161 M232R 157:161 M232R 157:161 A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. 36879070 9 93 theme prion 1673:1677 arg1 proteins 1679:1686 prion proteins 1673:1686 prion proteins 1673:1686 Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. 36879070 7 94 theme prion 1233:1237 arg1 manner 1256:1261 a prion strain-dependent manner 1231:1261 a prion strain-dependent manner 1231:1261 The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. 35094961 13 0 theme MS 1964:1965 arg1 patients 1967:1974 MS patients 1964:1974 MS patients 1964:1974 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 4 1 theme remitting 476:484 arg1 patients 489:496 24 untreated relapse remitting MS patients 455:496 24 untreated relapse remitting MS patients 455:496 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 9 2 theme immune 954:959 arg1 cells 961:965 blood immune cells 948:965 blood immune cells 948:965 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 17 3 theme research 2964:2971 arg1 FISM 2985:2988 FISM 2018/B/1 2985:2997 FISM 2018/B/1 2985:2997 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 17 3 theme research 2964:2971 arg1 fellowship 2973:2982 Society research fellowship 2956:2982 Society research fellowship (FISM 2018/B/1) 2956:2998 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 15 4 theme Piccio 2647:2652 arg1 L 2654:2654 Piccio L 2647:2654 Piccio L 2647:2654 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 19 5 theme Foundation 3228:3237 arg1 Neuroimmunology 3182:3196 Neuroimmunology 3182:3196 Neuroimmunology of the Barnes-Jewish Hospital Foundation 3182:3237 John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. 35094961 9 6 theme healthy 1064:1070 arg1 controls 1072:1079 healthy controls 1064:1079 healthy controls 1064:1079 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 19 7 theme Center 3166:3171 arg1 Chair 3173:3177 Center Chair 3166:3177 Center Chair 3166:3177 John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. 35094961 10 8 theme metabolome 1229:1238 arg1 methionine 1350:1359 methionine 1350:1359 methionine 1350:1359 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 10 8 theme metabolome 1229:1238 arg1 pathway 1269:1275 linoleate metabolic pathway 1249:1275 linoleate metabolic pathway 1249:1275 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 10 8 theme metabolome 1229:1238 arg1 chalcone 1303:1310 chalcone 1303:1310 chalcone 1303:1310 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 10 8 theme metabolome 1229:1238 arg1 dihydrochalcone 1313:1327 dihydrochalcone 1313:1327 dihydrochalcone 1313:1327 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 10 8 theme metabolome 1229:1238 arg1 perturbations 1200:1212 perturbations 1200:1212 perturbations 1200:1212 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 10 8 theme metabolome 1229:1238 arg1 biosynthesis 1289:1300 fatty acid biosynthesis 1278:1300 fatty acid biosynthesis 1278:1300 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 10 8 theme metabolome 1229:1238 arg1 4-nitrocatechol 1330:1344 4-nitrocatechol 1330:1344 4-nitrocatechol 1330:1344 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 15 9 theme Grant 2410:2414 arg1 TR000448 2429:2436 Grant Number # UL1 TR000448 2410:2436 Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH) 2410:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 11 10 theme metabolome-microbiome 1479:1499 arg1 correlation 1501:1511 a positive blood metabolome-microbiome correlation 1462:1511 a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites 1462:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 5 11 theme 16S 622:624 arg1 sequencing 650:659 16S and metagenomic shotgun sequencing 622:659 sequencing 650:659 Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. 35094961 15 12 dep Leon 2662:2665 arg1 Fund 2686:2689 Fund 2686:2689 Fund 2686:2689 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 12 dep Leon 2662:2665 arg1 the 2658:2660 the 2658:2660 the 2658:2660 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 14 13 theme biological 2078:2087 arg1 network 2089:2095 a potential important biological network 2056:2095 a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker 2056:2263 Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. 35094961 13 14 theme patients 1967:1974 arg1 metabolome 1950:1959 blood metabolome 1944:1959 blood metabolome 1944:1959 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 13 14 theme patients 1967:1974 arg1 microbiota 1921:1930 gut microbiota 1917:1930 gut microbiota 1917:1930 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 15 15 from Institutes 2456:2465 arg1 TR000448 2429:2436 Grant Number # UL1 TR000448 2410:2436 Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH) 2410:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 20 16 theme Health 3380:3385 arg1 Institutes 3366:3375 the National Institutes 3353:3375 the National Institutes of Health 3353:3385 The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 35094961 18 17 theme Rosalyn 3125:3131 arg1 Rosenthal-Dr 3133:3144 The Manny & Rosalyn Rosenthal-Dr 3113:3144 The Manny & Rosalyn Rosenthal-Dr 3113:3144 Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. 35094961 5 18 theme metagenomic 630:640 arg1 sequencing 650:659 16S and metagenomic shotgun sequencing 622:659 sequencing 650:659 Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. 35094961 11 19 theme increased 1671:1679 arg1 cell 1686:1689 increased Th17 cell 1671:1689 increased Th17 cell 1671:1689 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 15 20 theme Piccio 2714:2719 arg1 L 2721:2721 Piccio L 2714:2721 Piccio L 2714:2721 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 14 21 theme potential 2058:2066 arg1 network 2089:2095 a potential important biological network 2056:2095 a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker 2056:2263 Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. 35094961 15 22 theme Zhou 2639:2642 arg1 R01 2623:2625 R01 2623:2625 R01 2623:2625 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 22 theme Zhou 2639:2642 arg1 Y 2644:2644 Zhou Y 2639:2644 Zhou Y 2639:2644 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 3 23 theme host 281:284 arg1 system 293:298 the microbiome and host immune system 262:298 system 293:298 However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder. 35094961 17 24 theme Post-Doctoral 3044:3056 arg1 FG-190734474 3070:3081 FG-190734474 3070:3081 FG-190734474 3070:3081 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 17 24 theme Post-Doctoral 3044:3056 arg1 Fellowship 3058:3067 Society Post-Doctoral Fellowship 3036:3067 Society Post-Doctoral Fellowship (FG-190734474) 3036:3082 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 16 25 from Terry 2865:2869 arg1 donations 2841:2849 donations 2841:2849 donations from Whitelaw Terry, Jr. / Valerie Terry Fund 2841:2895 Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. 35094961 15 26 theme Clinical 2353:2360 arg1 Sciences 2380:2387 Clinical and Translational Sciences 2353:2387 Clinical and Translational Sciences 2353:2387 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 27 theme Number 2416:2421 arg1 TR000448 2429:2436 Grant Number # UL1 TR000448 2410:2436 Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH) 2410:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 9 28 from disability 1148:1157 arg1 patients 1165:1172 MS patients 1162:1172 MS patients 1162:1172 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 6 29 theme Flow 662:665 arg1 cytometry 667:675 Flow cytometry 662:675 Flow cytometry 662:675 Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. 35094961 1 30 contain has 106:108 arg2 pathophysiology 150:164 a complex genetic, immune and metabolic pathophysiology 110:164 a complex genetic, immune and metabolic pathophysiology 110:164 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 1 30 contain has 106:108 arg1 MS 102:103 MS 102:103 MS 102:103 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 1 30 contain has 106:108 arg1 sclerosis 91:99 BACKGROUND Multiple sclerosis 71:99 BACKGROUND Multiple sclerosis (MS) 71:104 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 14 31 theme data 2028:2031 arg1 integration 2033:2043 Multi-OMICS data integration 2016:2043 Multi-OMICS data integration 2016:2043 Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. 35094961 18 32 theme Manny 3117:3121 arg1 Rosenthal-Dr 3133:3144 The Manny & Rosalyn Rosenthal-Dr 3113:3144 The Manny & Rosalyn Rosenthal-Dr 3113:3144 Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. 35094961 13 33 theme multi-system 1889:1900 arg1 alterations 1902:1912 multi-system alterations 1889:1912 multi-system alterations in gut microbiota, immune and blood metabolome of MS patients 1889:1974 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 2 34 theme MS 215:216 arg1 pathogenesis 218:229 MS pathogenesis 215:229 MS pathogenesis 215:229 Recent studies implicated the gut microbiome in MS pathogenesis. 35094961 1 35 theme complex 112:118 arg1 pathophysiology 150:164 a complex genetic, immune and metabolic pathophysiology 110:164 a complex genetic, immune and metabolic pathophysiology 110:164 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 4 36 theme longitudinal 404:415 arg1 study 429:433 a six-month longitudinal multi-omics study 392:433 a six-month longitudinal multi-omics study of 49 participants 392:452 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 11 37 theme meat 1609:1612 arg1 servings 1614:1621 meat servings 1609:1621 meat servings 1609:1621 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 13 38 theme global 1979:1984 arg1 level 2009:2013 global and individual feature level 1979:2013 global and individual feature level 1979:2013 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 11 39 theme correlation 1581:1591 arg1 network 1593:1599 a potential correlation network 1569:1599 a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites 1569:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 10 40 theme linoleate 1249:1257 arg1 pathway 1269:1275 linoleate metabolic pathway 1249:1275 linoleate metabolic pathway 1249:1275 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 11 41 theme gut 1638:1640 arg1 microbe 1642:1648 decreased gut microbe 1628:1648 decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites 1628:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 8 42 theme dietary 875:881 arg1 pattern 883:889 the habitual dietary pattern 862:889 the habitual dietary pattern of study participants 862:911 A four-day food diary was recorded to capture the habitual dietary pattern of study participants. 35094961 10 43 theme fatty 1278:1282 arg1 biosynthesis 1289:1300 fatty acid biosynthesis 1278:1300 fatty acid biosynthesis 1278:1300 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 8 44 theme food 827:830 arg1 diary 832:836 A four-day food diary 816:836 A four-day food diary 816:836 A four-day food diary was recorded to capture the habitual dietary pattern of study participants. 35094961 1 45 theme BACKGROUND 71:80 arg1 MS 102:103 MS 102:103 MS 102:103 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 1 45 theme BACKGROUND 71:80 arg1 sclerosis 91:99 BACKGROUND Multiple sclerosis 71:99 BACKGROUND Multiple sclerosis (MS) 71:104 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 18 46 theme & 3123:3123 arg1 Rosenthal-Dr 3133:3144 The Manny & Rosalyn Rosenthal-Dr 3113:3144 The Manny & Rosalyn Rosenthal-Dr 3113:3144 Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. 35094961 4 47 theme untreated 458:466 arg1 patients 489:496 24 untreated relapse remitting MS patients 455:496 24 untreated relapse remitting MS patients 455:496 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 6 48 theme immune 708:713 arg1 populations 720:730 blood immune cell populations 702:730 blood immune cell populations 702:730 Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. 35094961 13 49 from alterations 1902:1912 arg1 immune 1933:1938 immune 1933:1938 immune 1933:1938 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 13 49 from alterations 1902:1912 arg1 metabolome 1950:1959 blood metabolome 1944:1959 blood metabolome 1944:1959 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 13 49 from alterations 1902:1912 arg1 microbiota 1921:1930 gut microbiota 1917:1930 gut microbiota 1917:1930 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 15 50 dep Award 2568:2572 arg1 R01 2623:2625 R01 2623:2625 R01 2623:2625 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 50 dep Award 2568:2572 arg1 Leon 2662:2665 Leon 2662:2665 Leon 2662:2665 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 50 dep Award 2568:2572 arg1 Felman 2679:2684 Felman 2679:2684 Felman 2679:2684 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 50 dep Award 2568:2572 arg1 Y 2644:2644 Zhou Y 2639:2644 Zhou Y 2639:2644 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 8 51 theme participants 900:911 arg1 pattern 883:889 the habitual dietary pattern 862:889 the habitual dietary pattern of study participants 862:911 A four-day food diary was recorded to capture the habitual dietary pattern of study participants. 35094961 11 52 theme blood 1473:1477 arg1 correlation 1501:1511 a positive blood metabolome-microbiome correlation 1462:1511 a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites 1462:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 0 53 from interactions 35:46 arg1 sclerosis 60:68 multiple sclerosis 51:68 multiple sclerosis 51:68 Alterations of host-gut microbiome interactions in multiple sclerosis. 35094961 9 54 theme MS 1162:1163 arg1 patients 1165:1172 MS patients 1162:1172 MS patients 1162:1172 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 11 55 theme Specific 1520:1527 arg1 analysis 1549:1556 Specific feature association analysis 1520:1556 Specific feature association analysis 1520:1556 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 5 56 theme microbiome 561:570 arg1 composition 572:582 Gut microbiome composition 557:582 Gut microbiome composition 557:582 Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. 35094961 16 57 theme Career 2790:2795 arg1 Fellowship 2808:2817 Career Transition Fellowship 2790:2817 the National MS Society Career Transition Fellowship (TA-180531003) 2766:2832 Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. 35094961 4 58 theme matched 520:526 arg1 individuals 544:554 matched healthy control individuals 520:554 matched healthy control individuals 520:554 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 11 59 theme potential 1571:1579 arg1 network 1593:1599 a potential correlation network 1569:1599 a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites 1569:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 0 60 theme host-gut 15:22 arg1 Alterations 0:10 Alterations 0:10 Alterations of host-gut 0:22 Alterations of host-gut microbiome interactions in multiple sclerosis. 35094961 18 61 theme Anne 3085:3088 arg1 Cross 3090:3094 Anne Cross 3085:3094 Anne Cross 3085:3094 Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. 35094961 17 62 dep Sclerosis 2946:2954 arg1 FISM 2985:2988 FISM 2018/B/1 2985:2997 FISM 2018/B/1 2985:2997 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 17 62 dep Sclerosis 2946:2954 arg1 fellowship 2973:2982 Society research fellowship 2956:2982 Society research fellowship (FISM 2018/B/1) 2956:2998 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 17 62 dep Sclerosis 2946:2954 arg1 FG-190734474 3070:3081 FG-190734474 3070:3081 FG-190734474 3070:3081 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 17 62 dep Sclerosis 2946:2954 arg1 Fellowship 3058:3067 Society Post-Doctoral Fellowship 3036:3067 Society Post-Doctoral Fellowship (FG-190734474) 3036:3082 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 4 63 theme control 536:542 arg1 individuals 544:554 matched healthy control individuals 520:554 matched healthy control individuals 520:554 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 9 64 from degree 1138:1143 arg1 patients 1165:1172 MS patients 1162:1172 MS patients 1162:1172 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 13 65 theme individual 1990:1999 arg1 level 2009:2013 global and individual feature level 1979:2013 global and individual feature level 1979:2013 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 4 66 dep age 505:507 arg1 individuals 544:554 matched healthy control individuals 520:554 matched healthy control individuals 520:554 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 14 67 theme meat-associated 2136:2150 arg1 metabolite 2158:2167 meat-associated blood metabolite 2136:2167 meat-associated blood metabolite 2136:2167 Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. 35094961 20 68 theme National 3357:3364 arg1 Institutes 3366:3375 the National Institutes 3353:3375 the National Institutes of Health 3353:3385 The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 35094961 13 69 theme blood 1944:1948 arg1 metabolome 1950:1959 blood metabolome 1944:1959 blood metabolome 1944:1959 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 7 70 theme untargeted 796:805 arg1 UPLC-MS 807:813 untargeted UPLC-MS 796:813 untargeted UPLC-MS 796:813 Circulating metabolites were profiled by untargeted UPLC-MS. 35094961 20 71 theme authors 3288:3294 arg1 content 3244:3250 The content 3240:3250 The content 3240:3250 The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 35094961 20 71 theme authors 3288:3294 arg1 responsibility 3266:3279 the responsibility 3262:3279 the responsibility of the authors 3262:3294 The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 35094961 11 72 theme meat-associated 1716:1730 arg1 metabolites 1738:1748 meat-associated blood metabolites 1716:1748 meat-associated blood metabolites 1716:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 0 73 theme multiple 51:58 arg1 sclerosis 60:68 multiple sclerosis 51:68 multiple sclerosis 51:68 Alterations of host-gut microbiome interactions in multiple sclerosis. 35094961 10 74 theme MS 1175:1176 arg1 patients 1178:1185 MS patients 1175:1185 MS patients 1175:1185 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 14 75 theme circulating 2230:2240 arg1 marker 2258:2263 circulating proinflammatory marker 2230:2263 circulating proinflammatory marker 2230:2263 Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. 35094961 15 76 theme St. 2330:2332 arg1 Institute 2340:2348 St. Louis Institute 2330:2348 St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH) 2330:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 77 theme MS 2701:2702 arg1 Research 2704:2711 Human MS Research 2695:2711 Human MS Research (Piccio L and Cross AH) 2695:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 10 78 theme blood 1223:1227 arg1 metabolome 1229:1238 their blood metabolome 1217:1238 their blood metabolome 1217:1238 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 14 79 theme meat 2108:2111 arg1 intakes 2113:2119 meat intakes 2108:2119 meat intakes 2108:2119 Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. 35094961 20 80 theme official 3335:3342 arg1 views 3344:3348 the official views 3331:3348 the official views of the National Institutes of Health 3331:3385 The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 35094961 11 81 dep thetaiotaomicron 1653:1668 arg1 B. 1650:1651 B. 1650:1651 B. 1650:1651 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 9 82 from microbiota 1086:1095 arg1 cells 961:965 blood immune cells 948:965 blood immune cells 948:965 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 6 83 theme cytokine 736:743 arg1 profiles 745:752 cytokine profiles 736:752 cytokine profiles 736:752 Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. 35094961 17 84 theme Multiple 2937:2944 arg1 Sclerosis 2946:2954 the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474) 2925:3082 Sclerosis 2946:2954 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 9 85 theme blood 948:952 arg1 cells 961:965 blood immune cells 948:965 blood immune cells 948:965 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 5 86 theme shotgun 642:648 arg1 sequencing 650:659 16S and metagenomic shotgun sequencing 622:659 sequencing 650:659 Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. 35094961 11 87 theme metabolites 1738:1748 arg1 thetaiotaomicron 1653:1668 thetaiotaomicron 1653:1668 thetaiotaomicron 1653:1668 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 11 87 theme metabolites 1738:1748 arg1 cell 1686:1689 increased Th17 cell 1671:1689 increased Th17 cell 1671:1689 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 11 87 theme metabolites 1738:1748 arg1 abundance 1703:1711 greater abundance 1695:1711 greater abundance of meat-associated blood metabolites 1695:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 17 88 theme Society 2956:2962 arg1 research 2964:2971 Society research 2956:2971 Society research fellowship (FISM 2018/B/1) 2956:2998 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 15 89 theme National 2478:2485 arg1 Health 2470:2475 Health 2470:2475 Health 2470:2475 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 89 theme National 2478:2485 arg1 Center 2487:2492 National Center 2478:2492 National Center for Advancing Translational Sciences 2478:2529 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 90 theme Health 2470:2475 arg1 Institutes 2456:2465 the National Institutes 2443:2465 the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH) 2443:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 4 91 theme six-month 394:402 arg1 study 429:433 a six-month longitudinal multi-omics study 392:433 a six-month longitudinal multi-omics study of 49 participants 392:452 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 16 92 dep Cantoni 2738:2744 arg1 C. 2746:2747 Cantoni C. 2738:2747 Cantoni C. 2738:2747 Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. 35094961 9 93 theme metagenomic 968:978 arg1 analysis 980:987 metagenomic analysis 968:987 metagenomic analysis 968:987 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 15 94 dep Y 2644:2644 arg1 L 2654:2654 Piccio L 2647:2654 Piccio L 2647:2654 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 95 theme Sciences 2380:2387 arg1 Institute 2340:2348 St. Louis Institute 2330:2348 St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH) 2330:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 96 theme # 2423:2423 arg1 TR000448 2429:2436 Grant Number # UL1 TR000448 2410:2436 Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH) 2410:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 97 theme Cross 2727:2731 arg1 AH 2733:2734 Cross AH 2727:2734 Cross AH 2727:2734 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 14 98 theme important 2068:2076 arg1 network 2089:2095 a potential important biological network 2056:2095 a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker 2056:2263 Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. 35094961 13 99 dep INTERPRETATION 1853:1866 arg1 identified 1878:1887 identified 1878:1887 identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level 1878:2013 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 11 100 theme Global 1362:1367 arg1 correlations 1369:1380 Global correlations 1362:1380 Global correlations between multi-omics 1362:1400 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 11 101 theme Th17 1681:1684 arg1 cell 1686:1689 increased Th17 cell 1671:1689 increased Th17 cell 1671:1689 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 3 102 theme immune 286:291 arg1 system 293:298 the microbiome and host immune system 262:298 system 293:298 However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder. 35094961 4 103 theme participants 441:452 arg1 study 429:433 a six-month longitudinal multi-omics study 392:433 a six-month longitudinal multi-omics study of 49 participants 392:452 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 9 104 from patients 1165:1172 arg1 degree 1138:1143 degree 1138:1143 degree of disability in MS patients 1138:1172 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 9 105 theme gut 1012:1014 arg1 microbiota 1016:1025 gut microbiota 1012:1025 gut microbiota 1012:1025 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 10 106 theme acid 1284:1287 arg1 biosynthesis 1289:1300 fatty acid biosynthesis 1278:1300 fatty acid biosynthesis 1278:1300 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 17 107 theme Multiple 3017:3024 arg1 Sclerosis 3026:3034 the National Multiple Sclerosis 3004:3034 the National Multiple Sclerosis 3004:3034 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 15 108 theme Translational 2366:2378 arg1 Sciences 2380:2387 Clinical and Translational Sciences 2353:2387 Clinical and Translational Sciences 2353:2387 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 109 theme Louis 2334:2338 arg1 Institute 2340:2348 St. Louis Institute 2330:2348 St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH) 2330:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 4 110 dep METHODS 371:377 arg1 performed 382:390 performed 382:390 performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals 382:554 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 13 111 theme gut 1917:1919 arg1 microbiota 1921:1930 gut microbiota 1917:1930 gut microbiota 1917:1930 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 17 112 theme Society 3036:3042 arg1 FG-190734474 3070:3081 FG-190734474 3070:3081 FG-190734474 3070:3081 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 17 112 theme Society 3036:3042 arg1 Fellowship 3058:3067 Society Post-Doctoral Fellowship 3036:3067 Society Post-Doctoral Fellowship (FG-190734474) 3036:3082 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 19 113 from MS 3163:3164 arg1 Neuroimmunology 3182:3196 Neuroimmunology 3182:3196 Neuroimmunology of the Barnes-Jewish Hospital Foundation 3182:3237 John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. 35094961 14 114 theme Multi-OMICS 2016:2026 arg1 integration 2033:2043 Multi-OMICS data integration 2016:2043 Multi-OMICS data integration 2016:2043 Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. 35094961 4 115 theme multi-omics 417:427 arg1 study 429:433 a six-month longitudinal multi-omics study 392:433 a six-month longitudinal multi-omics study of 49 participants 392:452 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 9 116 theme MS 1040:1041 arg1 patients 1043:1050 MS patients 1040:1050 MS patients 1040:1050 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 1 117 theme genetic 120:126 arg1 pathophysiology 150:164 a complex genetic, immune and metabolic pathophysiology 110:164 a complex genetic, immune and metabolic pathophysiology 110:164 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 12 118 theme control 1832:1838 arg1 individuals 1840:1850 control individuals 1832:1850 control individuals 1832:1850 The microbiome and metabolome profiles remained stable over six months in MS and control individuals. 35094961 9 119 from changes 937:943 arg1 cells 961:965 blood immune cells 948:965 blood immune cells 948:965 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 11 120 theme immune-microbiome 1427:1443 arg1 relationship 1445:1456 a disrupted immune-microbiome relationship 1415:1456 a disrupted immune-microbiome relationship 1415:1456 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 10 121 theme metabolic 1259:1267 arg1 pathway 1269:1275 linoleate metabolic pathway 1249:1275 linoleate metabolic pathway 1249:1275 MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. 35094961 1 122 theme immune 129:134 arg1 pathophysiology 150:164 a complex genetic, immune and metabolic pathophysiology 110:164 a complex genetic, immune and metabolic pathophysiology 110:164 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 15 123 theme Translational 2508:2520 arg1 Sciences 2522:2529 Advancing Translational Sciences 2498:2529 Advancing Translational Sciences 2498:2529 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 11 124 theme decreased 1628:1636 arg1 microbe 1642:1648 decreased gut microbe 1628:1648 decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites 1628:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 15 125 theme Tarr 2613:2616 arg1 PI 2618:2619 Tarr PI 2613:2619 Tarr PI 2613:2619 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 125 theme Tarr 2613:2616 arg1 Award 2568:2572 Award 2568:2572 Award 2568:2572 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 1 126 theme metabolic 140:148 arg1 pathophysiology 150:164 a complex genetic, immune and metabolic pathophysiology 110:164 a complex genetic, immune and metabolic pathophysiology 110:164 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 4 127 dep performed 382:390 arg1 race 515:518 race 515:518 race 515:518 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 4 127 dep performed 382:390 arg1 sex 510:512 sex 510:512 sex 510:512 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 4 127 dep performed 382:390 arg1 patients 489:496 24 untreated relapse remitting MS patients 455:496 24 untreated relapse remitting MS patients 455:496 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 4 127 dep performed 382:390 arg1 age 505:507 25 age 502:507 25 age 502:507 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 9 128 dep identified 989:998 arg1 decreased 1027:1035 decreased 1027:1035 identified a number of gut microbiota decreased in MS patients compared to healthy controls 989:1079 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 8 129 theme habitual 866:873 arg1 pattern 883:889 the habitual dietary pattern 862:889 the habitual dietary pattern of study participants 862:911 A four-day food diary was recorded to capture the habitual dietary pattern of study participants. 35094961 4 130 theme relapse 468:474 arg1 patients 489:496 24 untreated relapse remitting MS patients 455:496 24 untreated relapse remitting MS patients 455:496 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 6 131 theme cell 715:718 arg1 populations 720:730 blood immune cell populations 702:730 blood immune cell populations 702:730 Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. 35094961 8 132 theme four-day 818:825 arg1 diary 832:836 A four-day food diary 816:836 A four-day food diary 816:836 A four-day food diary was recorded to capture the habitual dietary pattern of study participants. 35094961 11 133 theme feature 1529:1535 arg1 analysis 1549:1556 Specific feature association analysis 1520:1556 Specific feature association analysis 1520:1556 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 1 134 theme Multiple 82:89 arg1 MS 102:103 MS 102:103 MS 102:103 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 1 134 theme Multiple 82:89 arg1 sclerosis 91:99 BACKGROUND Multiple sclerosis 71:99 BACKGROUND Multiple sclerosis (MS) 71:104 BACKGROUND Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. 35094961 4 135 theme MS 486:487 arg1 patients 489:496 24 untreated relapse remitting MS patients 455:496 24 untreated relapse remitting MS patients 455:496 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 11 136 theme disrupted 1417:1425 arg1 relationship 1445:1456 a disrupted immune-microbiome relationship 1415:1456 a disrupted immune-microbiome relationship 1415:1456 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 6 137 theme blood 702:706 arg1 populations 720:730 blood immune cell populations 702:730 blood immune cell populations 702:730 Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. 35094961 5 138 theme Gut 557:559 arg1 composition 572:582 Gut microbiome composition 557:582 Gut microbiome composition 557:582 Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. 35094961 8 139 theme study 894:898 arg1 participants 900:911 study participants 894:911 study participants 894:911 A four-day food diary was recorded to capture the habitual dietary pattern of study participants. 35094961 16 140 theme Transition 2797:2806 arg1 Fellowship 2808:2817 Career Transition Fellowship 2790:2817 the National MS Society Career Transition Fellowship (TA-180531003) 2766:2832 Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. 35094961 4 141 theme healthy 528:534 arg1 individuals 544:554 matched healthy control individuals 520:554 matched healthy control individuals 520:554 METHODS We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. 35094961 12 142 theme microbiome 1755:1764 arg1 profiles 1781:1788 The microbiome and metabolome profiles 1751:1788 profiles 1781:1788 The microbiome and metabolome profiles remained stable over six months in MS and control individuals. 35094961 6 143 used used 681:684 arg2 cytometry 667:675 Flow cytometry 662:675 Flow cytometry 662:675 Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. 35094961 11 144 theme association 1537:1547 arg1 analysis 1549:1556 Specific feature association analysis 1520:1556 Specific feature association analysis 1520:1556 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 16 145 dep Society 2782:2788 arg1 Fellowship 2808:2817 Career Transition Fellowship 2790:2817 the National MS Society Career Transition Fellowship (TA-180531003) 2766:2832 Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. 35094961 14 146 theme blood 2152:2156 arg1 metabolite 2158:2167 meat-associated blood metabolite 2136:2167 meat-associated blood metabolite 2136:2167 Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. 35094961 12 147 theme metabolome 1770:1779 arg1 profiles 1781:1788 The microbiome and metabolome profiles 1751:1788 profiles 1781:1788 The microbiome and metabolome profiles remained stable over six months in MS and control individuals. 35094961 15 148 theme National 2447:2454 arg1 Institutes 2456:2465 the National Institutes 2443:2465 the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH) 2443:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 9 149 theme microbiota 1016:1025 arg1 number 1002:1007 a number 1000:1007 a number of gut microbiota 1000:1025 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 2 150 theme Recent 167:172 arg1 studies 174:180 Recent studies 167:180 Recent studies 167:180 Recent studies implicated the gut microbiome in MS pathogenesis. 35094961 13 151 theme feature 2001:2007 arg1 level 2009:2013 global and individual feature level 1979:2013 global and individual feature level 1979:2013 INTERPRETATION Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. 35094961 9 152 theme disability 1148:1157 arg1 degree 1138:1143 degree 1138:1143 degree of disability in MS patients 1138:1172 FINDINGS Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. 35094961 17 153 theme National 3008:3015 arg1 Sclerosis 3026:3034 the National Multiple Sclerosis 3004:3034 the National Multiple Sclerosis 3004:3034 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 16 154 dep Terry 2865:2869 arg1 Terry 2886:2890 Terry 2886:2890 Terry 2886:2890 Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. 35094961 16 154 dep Terry 2865:2869 arg1 Fund 2892:2895 Fund 2892:2895 Whitelaw Terry, Jr. / Valerie Terry Fund 2856:2895 Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. 35094961 14 155 theme proinflammatory 2242:2256 arg1 marker 2258:2263 circulating proinflammatory marker 2230:2263 circulating proinflammatory marker 2230:2263 Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. 35094961 11 156 theme greater 1695:1701 arg1 abundance 1703:1711 greater abundance 1695:1711 greater abundance of meat-associated blood metabolites 1695:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 15 157 theme Human 2695:2699 arg1 Research 2704:2711 Human MS Research 2695:2711 Human MS Research (Piccio L and Cross AH) 2695:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 158 theme UL1 2425:2427 arg1 TR000448 2429:2436 Grant Number # UL1 TR000448 2410:2436 Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH) 2410:2735 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 20 159 theme Institutes 3366:3375 arg1 views 3344:3348 the official views 3331:3348 the official views of the National Institutes of Health 3331:3385 The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 35094961 17 160 dep Ghezzi 2898:2903 arg1 L. 2905:2906 Ghezzi L. 2898:2906 Ghezzi L. 2898:2906 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 2 161 theme gut 197:199 arg1 microbiome 201:210 the gut microbiome 193:210 the gut microbiome 193:210 Recent studies implicated the gut microbiome in MS pathogenesis. 35094961 15 162 dep Research 2704:2711 arg1 L 2721:2721 Piccio L 2714:2721 Piccio L 2714:2721 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 15 162 dep Research 2704:2711 arg1 AH 2733:2734 Cross AH 2727:2734 Cross AH 2727:2734 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 17 163 theme Italian 2929:2935 arg1 Sclerosis 2946:2954 the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474) 2925:3082 Sclerosis 2946:2954 Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). 35094961 11 164 theme positive 1464:1471 arg1 correlation 1501:1511 a positive blood metabolome-microbiome correlation 1462:1511 a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites 1462:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 15 165 theme Advancing 2498:2506 arg1 Sciences 2522:2529 Advancing Translational Sciences 2498:2529 Advancing Translational Sciences 2498:2529 FUNDING This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). 35094961 11 166 theme blood 1732:1736 arg1 metabolites 1738:1748 meat-associated blood metabolites 1716:1748 meat-associated blood metabolites 1716:1748 Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. 35094961 7 167 theme Circulating 755:765 arg1 metabolites 767:777 Circulating metabolites 755:777 Circulating metabolites 755:777 Circulating metabolites were profiled by untargeted UPLC-MS. 35469018 7 0 theme cancer-associated 1263:1279 arg1 dysregulation 1288:1300 cancer-associated muscle dysregulation 1263:1300 cancer-associated muscle dysregulation 1263:1300 Our findings link O-GlcNAcylation to muscular protein homoeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation. 35469018 1 1 from decline 98:104 arg1 strength 147:154 low muscular strength 134:154 low muscular strength 134:154 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 1 1 from decline 98:104 arg1 mass 125:128 skeletal muscle mass 109:128 skeletal muscle mass 109:128 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 5 2 theme cancer 886:891 arg1 setting 875:881 the setting 871:881 the setting of cancer 871:891 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 7 3 theme muscle 1281:1286 arg1 dysregulation 1288:1300 cancer-associated muscle dysregulation 1263:1300 cancer-associated muscle dysregulation 1263:1300 Our findings link O-GlcNAcylation to muscular protein homoeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation. 35469018 1 4 from factors 171:177 arg1 cancers 197:203 advanced human cancers 182:203 advanced human cancers 182:203 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 5 5 theme desmin 1009:1014 arg1 filaments 1016:1024 desmin filaments 1009:1024 desmin filaments 1009:1024 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 5 6 theme increasing 902:911 arg1 RYR1 913:916 increasing RYR1 902:916 increasing RYR1 902:916 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 5 7 theme Suppressed 841:850 arg1 O-GlcNAcylation 852:866 Suppressed O-GlcNAcylation 841:866 Suppressed O-GlcNAcylation 841:866 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 6 8 theme tumour-bearing 1131:1144 arg1 mice 1146:1149 tumour-bearing mice 1131:1149 tumour-bearing mice 1131:1149 This was associated with reduced skeletal muscle mass and contractility in tumour-bearing mice. 35469018 5 9 theme myofibrillar 1030:1041 arg1 destruction 1043:1053 myofibrillar destruction 1030:1053 myofibrillar destruction 1030:1053 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 1 10 theme advanced 182:189 arg1 cancers 197:203 advanced human cancers 182:203 advanced human cancers 182:203 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 3 11 theme receptor 461:468 arg1 O-GlcNAcylation 432:446 O-GlcNAcylation 432:446 O-GlcNAcylation of ryanodine receptor 1 (RYR1) 432:477 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 6 12 from mass 1105:1108 arg1 mice 1146:1149 tumour-bearing mice 1131:1149 tumour-bearing mice 1131:1149 This was associated with reduced skeletal muscle mass and contractility in tumour-bearing mice. 35469018 7 13 theme dysregulation 1288:1300 arg1 mechanism 1250:1258 a mechanism 1248:1258 a mechanism of cancer-associated muscle dysregulation 1248:1300 Our findings link O-GlcNAcylation to muscular protein homoeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation. 35469018 2 14 theme protein 290:296 arg1 modification 298:309 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 250:309 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 250:309 Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). 35469018 7 15 attach link 1165:1168 arg2 findings 1156:1163 Our findings 1152:1163 Our findings 1152:1163 Our findings link O-GlcNAcylation to muscular protein homoeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation. 35469018 7 15 attach link 1165:1168 arg1 contractility 1223:1235 contractility 1223:1235 contractility 1223:1235 Our findings link O-GlcNAcylation to muscular protein homoeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation. 35469018 7 15 attach link 1165:1168 arg1 homoeostasis 1206:1217 muscular protein homoeostasis 1189:1217 muscular protein homoeostasis 1189:1217 Our findings link O-GlcNAcylation to muscular protein homoeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation. 35469018 1 16 theme human 191:195 arg1 cancers 197:203 advanced human cancers 182:203 advanced human cancers 182:203 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 3 17 theme RYR1 652:655 arg1 abundance 657:665 increased RYR1 abundance 642:665 increased RYR1 abundance 642:665 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 4 18 theme HIF1A-dependent 768:782 arg1 activation 797:806 HIF1A-dependent OGT promoter activation 768:806 HIF1A-dependent OGT promoter activation 768:806 We further found that muscular protein O-GlcNAcylation was regulated by hypoxia and lactate through HIF1A-dependent OGT promoter activation and was elevated after exercise. 35469018 0 19 theme Cancer-cell-secreted 0:19 arg1 miR-122 21:27 Cancer-cell-secreted miR-122 0:27 Cancer-cell-secreted miR-122 0:27 Cancer-cell-secreted miR-122 suppresses O-GlcNAcylation to promote skeletal muscle proteolysis. 35469018 6 20 theme muscle 1098:1103 arg1 mass 1105:1108 reduced skeletal muscle mass 1081:1108 reduced skeletal muscle mass 1081:1108 This was associated with reduced skeletal muscle mass and contractility in tumour-bearing mice. 35469018 6 21 from contractility 1114:1126 arg1 mice 1146:1149 tumour-bearing mice 1131:1149 tumour-bearing mice 1131:1149 This was associated with reduced skeletal muscle mass and contractility in tumour-bearing mice. 35469018 1 22 theme skeletal 109:116 arg1 mass 125:128 skeletal muscle mass 109:128 skeletal muscle mass 109:128 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 6 23 theme skeletal 1089:1096 arg1 mass 1105:1108 reduced skeletal muscle mass 1081:1108 reduced skeletal muscle mass 1081:1108 This was associated with reduced skeletal muscle mass and contractility in tumour-bearing mice. 35469018 1 24 theme muscle 118:123 arg1 mass 125:128 skeletal muscle mass 109:128 skeletal muscle mass 109:128 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 5 25 theme cytosolic 933:941 arg1 Ca2+ 943:946 higher cytosolic Ca2+ 926:946 higher cytosolic Ca2+ 926:946 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 5 26 theme higher 926:931 arg1 Ca2+ 943:946 higher cytosolic Ca2+ 926:946 higher cytosolic Ca2+ 926:946 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 6 27 theme reduced 1081:1087 arg1 mass 1105:1108 reduced skeletal muscle mass 1081:1108 reduced skeletal muscle mass 1081:1108 This was associated with reduced skeletal muscle mass and contractility in tumour-bearing mice. 35469018 5 28 from O-GlcNAcylation 852:866 arg1 setting 875:881 the setting 871:881 the setting of cancer 871:891 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 3 29 theme increased 642:650 arg1 abundance 657:665 increased RYR1 abundance 642:665 increased RYR1 abundance 642:665 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 2 30 theme O-GlcNAc 387:394 arg1 OGT 409:411 OGT 409:411 OGT 409:411 Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). 35469018 2 30 theme O-GlcNAc 387:394 arg1 transferase 396:406 O-GlcNAc transferase 387:406 O-GlcNAc transferase (OGT) 387:412 Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). 35469018 7 31 theme muscular 1189:1196 arg1 homoeostasis 1206:1217 muscular protein homoeostasis 1189:1217 muscular protein homoeostasis 1189:1217 Our findings link O-GlcNAcylation to muscular protein homoeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation. 35469018 2 32 theme O-linked 250:257 arg1 O-GlcNAc 280:287 O-GlcNAc 280:287 O-GlcNAc 280:287 Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). 35469018 2 32 theme O-linked 250:257 arg1 N-acetylglucosamine 259:277 O-linked N-acetylglucosamine 250:277 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 250:309 Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). 35469018 3 33 theme NEK10-mediated 493:506 arg1 phosphorylation 508:522 NEK10-mediated phosphorylation 493:522 NEK10-mediated phosphorylation 493:522 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 5 34 theme protease 960:967 arg1 activation 969:978 calpain protease activation 952:978 calpain protease activation 952:978 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 7 35 theme protein 1198:1204 arg1 homoeostasis 1206:1217 muscular protein homoeostasis 1189:1217 muscular protein homoeostasis 1189:1217 Our findings link O-GlcNAcylation to muscular protein homoeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation. 35469018 5 36 theme calpain 952:958 arg1 activation 969:978 calpain protease activation 952:978 calpain protease activation 952:978 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 0 37 theme muscle 76:81 arg1 proteolysis 83:93 skeletal muscle proteolysis 67:93 skeletal muscle proteolysis 67:93 Cancer-cell-secreted miR-122 suppresses O-GlcNAcylation to promote skeletal muscle proteolysis. 35469018 3 38 link K48-linked 538:547 arg1 ubiquitination 549:562 K48-linked ubiquitination 538:562 K48-linked ubiquitination 538:562 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 5 39 theme filaments 1016:1024 arg1 cleavage 997:1004 cleavage 997:1004 cleavage of desmin filaments 997:1024 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 5 39 theme filaments 1016:1024 arg1 destruction 1043:1053 myofibrillar destruction 1030:1053 myofibrillar destruction 1030:1053 Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. 35469018 0 40 theme skeletal 67:74 arg1 proteolysis 83:93 skeletal muscle proteolysis 67:93 skeletal muscle proteolysis 67:93 Cancer-cell-secreted miR-122 suppresses O-GlcNAcylation to promote skeletal muscle proteolysis. 35469018 2 41 theme breast 225:230 arg1 cancer 232:237 breast cancer 225:237 breast cancer 225:237 Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). 35469018 1 42 theme low 134:136 arg1 strength 147:154 low muscular strength 134:154 low muscular strength 134:154 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 4 43 theme OGT 784:786 arg1 activation 797:806 HIF1A-dependent OGT promoter activation 768:806 HIF1A-dependent OGT promoter activation 768:806 We further found that muscular protein O-GlcNAcylation was regulated by hypoxia and lactate through HIF1A-dependent OGT promoter activation and was elevated after exercise. 35469018 1 44 theme muscular 138:145 arg1 strength 147:154 low muscular strength 134:154 low muscular strength 134:154 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 2 45 theme extracellular-vesicle-encapsulated 329:362 arg1 miR-122 364:370 extracellular-vesicle-encapsulated miR-122 329:370 extracellular-vesicle-encapsulated miR-122 329:370 Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). 35469018 4 46 theme muscular 690:697 arg1 O-GlcNAcylation 707:721 muscular protein O-GlcNAcylation 690:721 muscular protein O-GlcNAcylation 690:721 We further found that muscular protein O-GlcNAcylation was regulated by hypoxia and lactate through HIF1A-dependent OGT promoter activation and was elevated after exercise. 35469018 3 47 theme miR-122-mediated 597:612 arg1 decrease 614:621 the miR-122-mediated decrease 593:621 the miR-122-mediated decrease in OGT 593:628 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 3 48 theme K48-linked 538:547 arg1 ubiquitination 549:562 K48-linked ubiquitination 538:562 K48-linked ubiquitination 538:562 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 3 49 from decrease 614:621 arg1 OGT 626:628 OGT 626:628 OGT 626:628 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 4 50 theme promoter 788:795 arg1 activation 797:806 HIF1A-dependent OGT promoter activation 768:806 HIF1A-dependent OGT promoter activation 768:806 We further found that muscular protein O-GlcNAcylation was regulated by hypoxia and lactate through HIF1A-dependent OGT promoter activation and was elevated after exercise. 35469018 2 51 link O-linked 250:257 arg1 O-GlcNAc 280:287 O-GlcNAc 280:287 O-GlcNAc 280:287 Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). 35469018 2 51 link O-linked 250:257 arg1 N-acetylglucosamine 259:277 O-linked N-acetylglucosamine 250:277 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 250:309 Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). 35469018 3 52 theme ryanodine 451:459 arg1 receptor 461:468 ryanodine receptor 1 451:470 ryanodine receptor 1 (RYR1) 451:477 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 3 52 theme ryanodine 451:459 arg1 RYR1 473:476 RYR1 473:476 RYR1 473:476 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 2 53 theme N-acetylglucosamine 259:277 arg1 modification 298:309 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 250:309 O-linked N-acetylglucosamine (O-GlcNAc) protein modification 250:309 Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). 35469018 1 54 theme prognostic 160:169 arg1 decline 98:104 A decline 96:104 A decline in skeletal muscle mass and low muscular strength 96:154 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 1 54 theme prognostic 160:169 arg1 factors 171:177 prognostic factors 160:177 prognostic factors in advanced human cancers 160:203 A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. 35469018 3 55 theme proteasomal 568:578 arg1 degradation 580:590 proteasomal degradation 568:590 proteasomal degradation 568:590 Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. 35469018 4 56 theme protein 699:705 arg1 O-GlcNAcylation 707:721 muscular protein O-GlcNAcylation 690:721 muscular protein O-GlcNAcylation 690:721 We further found that muscular protein O-GlcNAcylation was regulated by hypoxia and lactate through HIF1A-dependent OGT promoter activation and was elevated after exercise. 35536006 4 0 from sequencing 895:904 arg1 participants 927:938 290 healthy adult participants 909:938 290 healthy adult participants 909:938 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 1 1 theme coming 264:269 arg1 decades 271:277 the coming decades 260:277 the coming decades 260:277 Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. 35536006 12 2 theme antibiotic 2498:2507 arg1 genes 2520:2524 antibiotic resistance genes 2498:2524 antibiotic resistance genes 2498:2524 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 6 3 theme lowest 1280:1285 arg1 quartile 1287:1294 the lowest quartile 1276:1294 the lowest quartile of ARGs (low-ARG) 1276:1312 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 13 4 theme infectious 2866:2875 arg1 disease 2877:2883 infectious disease 2866:2883 infectious disease 2866:2883 Dietary interventions may be useful for lessening the burden of antimicrobial resistance and might ultimately motivate dietary guidelines which will consider how nutrition can reduce the impact of infectious disease. 35536006 11 5 theme human 2252:2256 arg1 microbiome 2262:2271 the human gut microbiome 2248:2271 shaping the human gut microbiome 2240:2271 Diet is a powerful method for shaping the human gut microbiome and may be a tractable method for lessening antibiotic resistance, and yet little is known about the relationship between diet and AMR. 35536006 4 6 theme knowledge 661:669 arg1 gap 671:673 this knowledge gap 656:673 this knowledge gap 656:673 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 9 7 theme health 1943:1948 arg1 systems 1955:1961 health care systems 1943:1961 health care systems 1943:1961 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 1 8 theme AMR-associated 197:210 arg1 consequences 212:223 AMR-associated consequences 197:223 AMR-associated consequences 197:223 Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. 35536006 4 9 theme healthy 913:919 arg1 participants 927:938 290 healthy adult participants 909:938 290 healthy adult participants 909:938 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 7 10 theme lifestyle 1621:1629 arg1 features 1631:1638 387 dietary, physiological, and lifestyle features 1589:1638 387 dietary, physiological, and lifestyle features 1589:1638 Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. 35536006 12 11 theme antibiotic 2640:2649 arg1 genes 2662:2666 fewer antibiotic resistance genes 2634:2666 fewer antibiotic resistance genes 2634:2666 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 9 12 theme public 1973:1978 arg1 community 1987:1995 the public health community 1969:1995 the public health community 1969:1995 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 4 13 theme food 703:706 arg1 FFQ 733:735 FFQ 733:735 FFQ; habitual diet 733:750 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 13 theme food 703:706 arg1 questionnaire 718:730 the food frequency questionnaire 699:730 the food frequency questionnaire (FFQ; habitual diet) 699:751 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 12 14 from protein 2622:2628 arg1 high 2590:2593 high 2590:2593 high 2590:2593 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 8 15 theme AMR 1860:1862 arg1 burden 1850:1855 the burden 1846:1855 the burden of AMR 1846:1862 These data suggest diet may be a potential method for reducing the burden of AMR. 35536006 4 16 theme metagenome 884:893 arg1 sequencing 895:904 shotgun metagenome sequencing 876:904 shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 876:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 3 17 theme antimicrobial 619:631 arg1 resistance 633:642 antimicrobial resistance 619:642 antimicrobial resistance 619:642 Diet is one method of intervention, and yet little is known about the association between diet and antimicrobial resistance. 35536006 4 18 dep FFQ 733:735 arg1 diet 747:750 habitual diet 738:750 FFQ; habitual diet 733:750 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 19 theme States 954:959 arg1 sequencing 895:904 shotgun metagenome sequencing 876:904 shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 876:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 0 20 theme U.S. 60:63 arg1 Adults 65:70 Healthy U.S. Adults 52:70 Healthy U.S. Adults 52:70 Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults. 35536006 5 21 theme AMR 1105:1107 arg1 mechanism 1092:1100 the most abundant and prevalent mechanism 1060:1100 the most abundant and prevalent mechanism of AMR 1060:1107 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 5 21 theme AMR 1105:1107 arg1 aminoglycosides 1039:1053 aminoglycosides 1039:1053 aminoglycosides 1039:1053 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 6 22 theme increased 1429:1437 arg1 abundances 1439:1448 increased abundances 1429:1448 increased abundances 1429:1448 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 8 23 theme potential 1816:1824 arg1 method 1826:1831 a potential method 1814:1831 a potential method for reducing the burden of AMR 1814:1862 These data suggest diet may be a potential method for reducing the burden of AMR. 35536006 8 23 theme potential 1816:1824 arg1 diet 1802:1805 diet 1802:1805 diet 1802:1805 These data suggest diet may be a potential method for reducing the burden of AMR. 35536006 1 24 theme morbidity 139:147 arg1 source 129:134 a significant source 115:134 a significant source of morbidity and mortality worldwide 115:171 Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. 35536006 12 25 theme resistance 2651:2660 arg1 genes 2662:2666 fewer antibiotic resistance genes 2634:2666 fewer antibiotic resistance genes 2634:2666 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 1 26 theme mortality 153:161 arg1 source 129:134 a significant source 115:134 a significant source of morbidity and mortality worldwide 115:171 Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. 35536006 11 27 theme powerful 2220:2227 arg1 Diet 2210:2213 Diet 2210:2213 Diet 2210:2213 Diet is a powerful method for shaping the human gut microbiome and may be a tractable method for lessening antibiotic resistance, and yet little is known about the relationship between diet and AMR. 35536006 11 27 theme powerful 2220:2227 arg1 method 2229:2234 a powerful method 2218:2234 a powerful method for shaping the human gut microbiome 2218:2271 Diet is a powerful method for shaping the human gut microbiome and may be a tractable method for lessening antibiotic resistance, and yet little is known about the relationship between diet and AMR. 35536006 0 28 from Association 0:10 arg1 Adults 65:70 Healthy U.S. Adults 52:70 Healthy U.S. Adults 52:70 Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults. 35536006 9 29 dep IMPORTANCE 1865:1874 arg1 resistance 1890:1899 Antimicrobial resistance 1876:1899 IMPORTANCE Antimicrobial resistance (AMR) 1865:1905 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 9 29 dep IMPORTANCE 1865:1874 arg1 AMR 1902:1904 AMR 1902:1904 AMR 1902:1904 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 7 30 theme phylogenetic 1711:1722 arg1 diversity 1724:1732 increased phylogenetic diversity 1701:1732 increased phylogenetic diversity of diet 1701:1740 Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. 35536006 7 31 theme machine 1561:1567 arg1 learning 1569:1576 machine learning 1561:1576 machine learning 1561:1576 Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. 35536006 10 32 theme human 2192:2196 arg1 microbiome 2198:2207 the human microbiome 2188:2207 the human microbiome 2188:2207 Humans carry antibiotic resistance in the microbes that live in and on us, collectively known as the human microbiome. 35536006 4 33 theme 24-h 757:760 arg1 tool 821:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 33 theme 24-h 757:760 arg1 recalls 770:776 24-h dietary recalls 757:776 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 757:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 2 34 theme gut 407:409 arg1 composition 388:398 the taxonomic composition 374:398 the taxonomic composition of the gut 374:409 Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). 35536006 13 35 theme resistance 2747:2756 arg1 burden 2723:2728 the burden 2719:2728 the burden of antimicrobial resistance 2719:2756 Dietary interventions may be useful for lessening the burden of antimicrobial resistance and might ultimately motivate dietary guidelines which will consider how nutrition can reduce the impact of infectious disease. 35536006 1 36 theme Antimicrobial 73:85 arg1 AMR 99:101 AMR 99:101 AMR 99:101 Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. 35536006 1 36 theme Antimicrobial 73:85 arg1 resistance 87:96 Antimicrobial resistance 73:96 Antimicrobial resistance (AMR) 73:102 Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. 35536006 4 37 theme Phenotyping 1006:1016 arg1 Study 1018:1022 Agriculture (USDA) Nutritional Phenotyping Study 975:1022 Agriculture (USDA) Nutritional Phenotyping Study 975:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 7 38 with associations 1644:1655 arg1 resistance 1676:1685 antimicrobial resistance 1662:1685 antimicrobial resistance 1662:1685 Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. 35536006 9 39 theme death 2052:2056 arg1 worldwide 2058:2066 death worldwide 2052:2066 death worldwide 2052:2066 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 4 40 theme habitual 738:745 arg1 diet 747:750 habitual diet 738:750 FFQ; habitual diet 733:750 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 10 41 from resistance 2115:2124 arg1 microbes 2133:2140 the microbes 2129:2140 the microbes that live in and on us 2129:2163 Humans carry antibiotic resistance in the microbes that live in and on us, collectively known as the human microbiome. 35536006 0 42 theme Diet 15:18 arg1 Association 0:10 Association 0:10 Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults. 0:71 Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults. 35536006 7 43 theme antimicrobial 1662:1674 arg1 resistance 1676:1685 antimicrobial resistance 1662:1685 antimicrobial resistance 1662:1685 Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. 35536006 2 44 theme resistant 496:504 arg1 ARGs 513:516 ARGs 513:516 ARGs 513:516 Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). 35536006 2 44 theme resistant 496:504 arg1 genes 506:510 antibiotic resistant genes 485:510 fewer antibiotic resistant genes (ARGs) 479:517 Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). 35536006 4 45 theme 24-h 807:810 arg1 tool 821:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 45 theme 24-h 807:810 arg1 recalls 770:776 24-h dietary recalls 757:776 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 757:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 0 46 theme Antimicrobial 24:36 arg1 Resistance 38:47 Antimicrobial Resistance 24:47 Antimicrobial Resistance 24:47 Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults. 35536006 2 47 theme antibiotic 485:494 arg1 ARGs 513:516 ARGs 513:516 ARGs 513:516 Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). 35536006 2 47 theme antibiotic 485:494 arg1 genes 506:510 antibiotic resistant genes 485:510 fewer antibiotic resistant genes (ARGs) 479:517 Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). 35536006 12 48 contain had 2630:2632 arg1 individuals 2541:2551 individuals 2541:2551 individuals who consumed diverse diets that were high in fiber and low in animal protein 2541:2628 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 12 48 contain had 2630:2632 arg2 genes 2662:2666 fewer antibiotic resistance genes 2634:2666 fewer antibiotic resistance genes 2634:2666 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 12 49 theme fewer 2634:2638 arg1 genes 2662:2666 fewer antibiotic resistance genes 2634:2666 fewer antibiotic resistance genes 2634:2666 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 9 50 theme coming 2075:2080 arg1 decades 2082:2088 the coming decades 2071:2088 the coming decades 2071:2088 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 11 51 dep shaping 2240:2246 arg1 microbiome 2262:2271 the human gut microbiome 2248:2271 shaping the human gut microbiome 2240:2271 Diet is a powerful method for shaping the human gut microbiome and may be a tractable method for lessening antibiotic resistance, and yet little is known about the relationship between diet and AMR. 35536006 6 52 from Clostridiaceae 1500:1513 arg1 abundances 1439:1448 increased abundances 1429:1448 increased abundances 1429:1448 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 11 53 theme tractable 2286:2294 arg1 method 2296:2301 a tractable method 2284:2301 a tractable method for lessening antibiotic resistance 2284:2337 Diet is a powerful method for shaping the human gut microbiome and may be a tractable method for lessening antibiotic resistance, and yet little is known about the relationship between diet and AMR. 35536006 12 54 theme genes 2520:2524 arg1 abundances 2484:2493 various abundances 2476:2493 various abundances of antibiotic resistance genes 2476:2524 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 9 55 from cause 2043:2047 arg1 decades 2082:2088 the coming decades 2071:2088 the coming decades 2071:2088 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 10 56 contain carry 2098:2102 arg1 Humans 2091:2096 Humans 2091:2096 Humans 2091:2096 Humans carry antibiotic resistance in the microbes that live in and on us, collectively known as the human microbiome. 35536006 10 56 contain carry 2098:2102 arg2 resistance 2115:2124 antibiotic resistance 2104:2124 antibiotic resistance 2104:2124 Humans carry antibiotic resistance in the microbes that live in and on us, collectively known as the human microbiome. 35536006 4 57 theme Automated 779:787 arg1 tool 821:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 57 theme Automated 779:787 arg1 recalls 770:776 24-h dietary recalls 757:776 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 757:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 2 58 theme taxonomic 378:386 arg1 composition 388:398 the taxonomic composition 374:398 the taxonomic composition of the gut 374:409 Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). 35536006 13 59 theme antimicrobial 2733:2745 arg1 resistance 2747:2756 antimicrobial resistance 2733:2756 antimicrobial resistance 2733:2756 Dietary interventions may be useful for lessening the burden of antimicrobial resistance and might ultimately motivate dietary guidelines which will consider how nutrition can reduce the impact of infectious disease. 35536006 5 60 theme fiber 1247:1251 arg1 intake 1253:1258 soluble fiber intake 1239:1258 soluble fiber intake 1239:1258 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 11 61 theme antibiotic 2317:2326 arg1 resistance 2328:2337 antibiotic resistance 2317:2337 antibiotic resistance 2317:2337 Diet is a powerful method for shaping the human gut microbiome and may be a tractable method for lessening antibiotic resistance, and yet little is known about the relationship between diet and AMR. 35536006 6 62 theme ARGs 1299:1302 arg1 quartile 1287:1294 the lowest quartile 1276:1294 the lowest quartile of ARGs (low-ARG) 1276:1312 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 6 63 from Individuals 1261:1271 arg1 quartile 1287:1294 the lowest quartile 1276:1294 the lowest quartile of ARGs (low-ARG) 1276:1312 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 9 64 with systems 1955:1961 arg1 community 1987:1995 the public health community 1969:1995 the public health community 1969:1995 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 12 65 theme resistance 2509:2518 arg1 genes 2520:2524 antibiotic resistance genes 2498:2524 antibiotic resistance genes 2498:2524 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 3 66 theme intervention 542:553 arg1 method 532:537 one method 528:537 one method of intervention 528:553 Diet is one method of intervention, and yet little is known about the association between diet and antimicrobial resistance. 35536006 6 67 theme anaerobes 1462:1470 arg1 abundances 1439:1448 increased abundances 1429:1448 increased abundances 1429:1448 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 5 68 theme total 1220:1224 arg1 calories 1226:1233 total calories 1220:1233 total calories 1220:1233 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 9 69 theme considerable 1920:1931 arg1 burden 1933:1938 a considerable burden 1918:1938 a considerable burden to health care systems, with the public health community 1918:1995 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 10 70 theme antibiotic 2104:2113 arg1 resistance 2115:2124 antibiotic resistance 2104:2124 antibiotic resistance 2104:2124 Humans carry antibiotic resistance in the microbes that live in and on us, collectively known as the human microbiome. 35536006 13 71 theme Dietary 2669:2675 arg1 interventions 2677:2689 Dietary interventions 2669:2689 Dietary interventions 2669:2689 Dietary interventions may be useful for lessening the burden of antimicrobial resistance and might ultimately motivate dietary guidelines which will consider how nutrition can reduce the impact of infectious disease. 35536006 12 72 from high 2590:2593 arg1 protein 2622:2628 animal protein 2615:2628 animal protein 2615:2628 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 12 72 from high 2590:2593 arg1 fiber 2598:2602 fiber 2598:2602 fiber 2598:2602 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 13 73 theme disease 2877:2883 arg1 impact 2856:2861 the impact 2852:2861 the impact of infectious disease 2852:2883 Dietary interventions may be useful for lessening the burden of antimicrobial resistance and might ultimately motivate dietary guidelines which will consider how nutrition can reduce the impact of infectious disease. 35536006 12 74 theme various 2476:2482 arg1 abundances 2484:2493 various abundances 2476:2493 various abundances of antibiotic resistance genes 2476:2524 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 9 75 theme care 1950:1953 arg1 systems 1955:1961 health care systems 1943:1961 health care systems 1943:1961 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 6 76 theme gut 1525:1527 arg1 microbiota 1529:1538 their gut microbiota 1519:1538 their gut microbiota 1519:1538 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 11 77 theme gut 2258:2260 arg1 microbiome 2262:2271 the human gut microbiome 2248:2271 shaping the human gut microbiome 2240:2271 Diet is a powerful method for shaping the human gut microbiome and may be a tractable method for lessening antibiotic resistance, and yet little is known about the relationship between diet and AMR. 35536006 6 78 theme more 1337:1340 arg1 fiber 1342:1346 significantly more fiber 1323:1346 significantly more fiber 1323:1346 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 1 79 dep continue 230:237 arg1 will 225:228 will 225:228 will 225:228 Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. 35536006 12 80 theme animal 2615:2620 arg1 protein 2622:2628 animal protein 2615:2628 animal protein 2615:2628 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 5 81 theme abundant 1069:1076 arg1 mechanism 1092:1100 the most abundant and prevalent mechanism 1060:1100 the most abundant and prevalent mechanism of AMR 1060:1107 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 5 81 theme abundant 1069:1076 arg1 aminoglycosides 1039:1053 aminoglycosides 1039:1053 aminoglycosides 1039:1053 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 7 82 theme physiological 1602:1614 arg1 features 1631:1638 387 dietary, physiological, and lifestyle features 1589:1638 387 dietary, physiological, and lifestyle features 1589:1638 Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. 35536006 4 83 theme microbiome 859:868 arg1 analysis 843:850 an analysis 840:850 an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 840:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 9 84 theme health 1980:1985 arg1 community 1987:1995 the public health community 1969:1995 the public health community 1969:1995 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 1 85 theme significant 117:127 arg1 source 129:134 a significant source 115:134 a significant source of morbidity and mortality worldwide 115:171 Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. 35536006 7 86 theme dietary 1593:1599 arg1 features 1631:1638 387 dietary, physiological, and lifestyle features 1589:1638 387 dietary, physiological, and lifestyle features 1589:1638 Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. 35536006 4 87 theme shotgun 876:882 arg1 sequencing 895:904 shotgun metagenome sequencing 876:904 shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 876:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 88 theme frequency 708:716 arg1 FFQ 733:735 FFQ 733:735 FFQ; habitual diet 733:750 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 88 theme frequency 708:716 arg1 questionnaire 718:730 the food frequency questionnaire 699:730 the food frequency questionnaire (FFQ; habitual diet) 699:751 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 6 89 from concomitant 1412:1422 arg1 microbiota 1529:1538 their gut microbiota 1519:1538 their gut microbiota 1519:1538 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 7 90 theme low-ARG 1762:1768 arg1 individuals 1770:1780 low-ARG individuals 1762:1780 low-ARG individuals 1762:1780 Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. 35536006 4 91 theme United 947:952 arg1 States 954:959 the United States 943:959 the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 943:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 91 theme United 947:952 arg1 Department 961:970 Department 961:970 Department 961:970 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 6 92 theme high-ARG 1380:1387 arg1 individuals 1389:1399 medium- and high-ARG individuals 1368:1399 medium- and high-ARG individuals 1368:1399 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 2 93 dep fewer 479:483 arg1 ARGs 513:516 ARGs 513:516 ARGs 513:516 Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). 35536006 2 93 dep fewer 479:483 arg1 genes 506:510 antibiotic resistant genes 485:510 fewer antibiotic resistant genes (ARGs) 479:517 Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). 35536006 12 94 from fiber 2598:2602 arg1 high 2590:2593 high 2590:2593 high 2590:2593 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 6 95 theme medium- 1368:1374 arg1 individuals 1389:1399 medium- and high-ARG individuals 1368:1399 medium- and high-ARG individuals 1368:1399 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 5 96 theme healthy 1118:1124 arg1 adults 1126:1131 these healthy adults 1112:1131 these healthy adults 1112:1131 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 13 97 theme dietary 2788:2794 arg1 guidelines 2796:2805 dietary guidelines 2788:2805 dietary guidelines which will consider how nutrition can reduce the impact of infectious disease 2788:2883 Dietary interventions may be useful for lessening the burden of antimicrobial resistance and might ultimately motivate dietary guidelines which will consider how nutrition can reduce the impact of infectious disease. 35536006 7 98 theme diet 1737:1740 arg1 diversity 1724:1732 increased phylogenetic diversity 1701:1732 increased phylogenetic diversity of diet 1701:1740 Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. 35536006 4 99 theme adult 921:925 arg1 participants 927:938 290 healthy adult participants 909:938 290 healthy adult participants 909:938 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 12 100 contain contained 2466:2474 arg2 abundances 2484:2493 various abundances 2476:2493 various abundances of antibiotic resistance genes 2476:2524 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 12 100 contain contained 2466:2474 arg1 individuals 2450:2460 healthy individuals 2442:2460 healthy individuals who contained various abundances of antibiotic resistance genes 2442:2524 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 12 101 theme healthy 2442:2448 arg1 individuals 2450:2460 healthy individuals 2442:2460 healthy individuals who contained various abundances of antibiotic resistance genes 2442:2524 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 5 102 theme prevalent 1082:1090 arg1 mechanism 1092:1100 the most abundant and prevalent mechanism 1060:1100 the most abundant and prevalent mechanism of AMR 1060:1107 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 5 102 theme prevalent 1082:1090 arg1 aminoglycosides 1039:1053 aminoglycosides 1039:1053 aminoglycosides 1039:1053 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 9 103 theme major 2037:2041 arg1 cause 2043:2047 a major cause 2035:2047 a major cause of death worldwide in the coming decades 2035:2088 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 9 103 theme major 2037:2041 arg1 AMR 2023:2025 AMR 2023:2025 AMR 2023:2025 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 5 104 from mechanism 1092:1100 arg1 adults 1126:1131 these healthy adults 1112:1131 these healthy adults 1112:1131 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 7 105 theme increased 1701:1709 arg1 diversity 1724:1732 increased phylogenetic diversity 1701:1732 increased phylogenetic diversity of diet 1701:1740 Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. 35536006 4 106 theme Nutritional 994:1004 arg1 Study 1018:1022 Agriculture (USDA) Nutritional Phenotyping Study 975:1022 Agriculture (USDA) Nutritional Phenotyping Study 975:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 12 107 theme diverse 2566:2572 arg1 diets 2574:2578 diverse diets 2566:2578 diverse diets that were high in fiber and low in animal protein 2566:2628 We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. 35536006 6 108 with concomitant 1412:1422 arg1 abundances 1439:1448 increased abundances 1429:1448 increased abundances 1429:1448 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 6 109 from microbiota 1529:1538 arg1 concomitant 1412:1422 concomitant 1412:1422 concomitant 1412:1422 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 4 110 theme Study 1018:1022 arg1 States 954:959 the United States 943:959 the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 943:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 110 theme Study 1018:1022 arg1 Department 961:970 Department 961:970 Department 961:970 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 9 111 theme worldwide 2058:2066 arg1 cause 2043:2047 a major cause 2035:2047 a major cause of death worldwide in the coming decades 2035:2088 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 9 111 theme worldwide 2058:2066 arg1 AMR 2023:2025 AMR 2023:2025 AMR 2023:2025 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 1 112 dep morbidity 139:147 arg1 worldwide 163:171 worldwide 163:171 worldwide 163:171 Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. 35536006 0 113 theme Resistance 38:47 arg1 Association 0:10 Association 0:10 Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults. 0:71 Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults. 35536006 4 114 theme Agriculture 975:985 arg1 Study 1018:1022 Agriculture (USDA) Nutritional Phenotyping Study 975:1022 Agriculture (USDA) Nutritional Phenotyping Study 975:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 115 theme Self-Administered 789:805 arg1 tool 821:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 115 theme Self-Administered 789:805 arg1 recalls 770:776 24-h dietary recalls 757:776 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 757:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 0 116 theme Healthy 52:58 arg1 Adults 65:70 Healthy U.S. Adults 52:70 Healthy U.S. Adults 52:70 Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults. 35536006 4 117 theme USDA 988:991 arg1 Study 1018:1022 Agriculture (USDA) Nutritional Phenotyping Study 975:1022 Agriculture (USDA) Nutritional Phenotyping Study 975:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 118 theme [ASA24® 812:818 arg1 tool 821:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 118 theme [ASA24® 812:818 arg1 recalls 770:776 24-h dietary recalls 757:776 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 757:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 10 119 dep live 2147:2150 arg1 microbes 2133:2140 the microbes 2129:2140 the microbes that live in and on us 2129:2163 Humans carry antibiotic resistance in the microbes that live in and on us, collectively known as the human microbiome. 35536006 9 120 theme Antimicrobial 1876:1888 arg1 resistance 1890:1899 Antimicrobial resistance 1876:1899 IMPORTANCE Antimicrobial resistance (AMR) 1865:1905 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 9 120 theme Antimicrobial 1876:1888 arg1 AMR 1902:1904 AMR 1902:1904 AMR 1902:1904 IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. 35536006 4 121 theme dietary 762:768 arg1 tool 821:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 Automated Self-Administered 24-h [ASA24®] tool 779:824 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 4 121 theme dietary 762:768 arg1 recalls 770:776 24-h dietary recalls 757:776 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study 757:1022 To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24®] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. 35536006 6 122 theme family 1493:1498 arg1 Clostridiaceae 1500:1513 the family Clostridiaceae 1489:1513 the family Clostridiaceae 1489:1513 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 35536006 5 123 theme soluble 1239:1245 arg1 intake 1253:1258 soluble fiber intake 1239:1258 soluble fiber intake 1239:1258 We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. 35536006 6 124 theme obligate 1453:1460 arg1 anaerobes 1462:1470 obligate anaerobes 1453:1470 obligate anaerobes 1453:1470 Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. 37217939 6 0 from relationship 909:920 arg1 cells 991:995 breast cancer BT-549 cells 970:995 breast cancer BT-549 cells 970:995 METHODS We used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells. 37217939 11 1 theme specific 1670:1677 arg1 sites 1679:1683 specific sites 1670:1683 specific sites 1670:1683 Our study showed that O-GlcNAcylation of eIF2α at specific sites suppresses HO-1 translation despite high levels of HMOX1 transcription. 37217939 2 2 theme key 336:338 arg1 role 340:343 a key role 334:343 a key role 334:343 To combat this stress, the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) is thought to play a key role as an antioxidant. 37217939 2 2 theme key 336:338 arg1 antioxidant 351:361 an antioxidant 348:361 an antioxidant 348:361 To combat this stress, the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) is thought to play a key role as an antioxidant. 37217939 12 3 theme site-specific 1818:1830 arg1 mutagenesis 1832:1842 site-specific mutagenesis 1818:1842 site-specific mutagenesis 1818:1842 We also found that eliminating eIF2α O-GlcNAcylation through site-specific mutagenesis improves cell recovery, migration, and reduces ROS accumulation by restoring HO-1 translation. 37217939 11 4 theme high 1721:1724 arg1 levels 1726:1731 high levels 1721:1731 high levels of HMOX1 transcription 1721:1754 Our study showed that O-GlcNAcylation of eIF2α at specific sites suppresses HO-1 translation despite high levels of HMOX1 transcription. 37217939 8 5 theme reactive 1231:1238 arg1 ROS 1256:1258 ROS 1256:1258 ROS 1256:1258 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 8 5 theme reactive 1231:1238 arg1 species 1247:1253 reactive oxygen species 1231:1253 reactive oxygen species (ROS) 1231:1259 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 2 6 dep oxygenase 271:279 arg1 HMOX1 284:288 HMOX1 284:288 HMOX1 284:288 To combat this stress, the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) is thought to play a key role as an antioxidant. 37217939 0 7 theme Extracellular 0:12 arg1 availability 23:34 Extracellular arginine availability 0:34 Extracellular arginine availability 0:34 Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis. 37217939 8 8 theme species 1247:1253 arg1 migration 1204:1212 migration 1204:1212 migration 1204:1212 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 8 8 theme species 1247:1253 arg1 accumulation 1215:1226 accumulation 1215:1226 accumulation of reactive oxygen species (ROS) 1215:1259 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 8 8 theme species 1247:1253 arg1 labeling 1276:1283 metabolic labeling 1266:1283 metabolic labeling during protein synthesis 1266:1308 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 8 8 theme species 1247:1253 arg1 effect 1154:1159 the effect 1150:1159 the effect of eIF2α O-GlcNAcylation on cell recovery 1150:1201 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 4 9 link O-linked 480:487 arg1 modification 522:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 480:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) 480:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 9 link O-linked 480:487 arg1 mechanism 609:617 a recently discovered cellular signaling mechanism 568:617 a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs) 568:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 14 10 theme clinical 2268:2275 arg1 implications 2277:2288 potential biological and clinical implications 2243:2288 potential biological and clinical implications 2243:2288 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 6 11 theme cancer 977:982 arg1 cells 991:995 breast cancer BT-549 cells 970:995 breast cancer BT-549 cells 970:995 METHODS We used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells. 37217939 8 12 theme different 1316:1324 arg1 conditions 1330:1339 different Arg conditions 1316:1339 different Arg conditions 1316:1339 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 6 13 dep O-GlcNAcylation 930:944 arg1 availability 954:965 availability 954:965 availability 954:965 METHODS We used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells. 37217939 8 14 theme metabolic 1266:1274 arg1 labeling 1276:1283 metabolic labeling 1266:1283 metabolic labeling during protein synthesis 1266:1308 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 7 15 theme eIF2α 1011:1015 arg1 O-GlcNAcylation 1017:1031 eIF2α O-GlcNAcylation 1011:1031 eIF2α O-GlcNAcylation 1011:1031 We validated eIF2α O-GlcNAcylation through site-specific mutagenesis and azido sugar N-azidoacetylglucosamine-tetraacylated labeling. 37217939 13 16 theme effector 1982:1989 arg1 ATF4 1991:1994 the metabolic stress effector ATF4 1961:1994 the metabolic stress effector ATF4 1961:1994 However, the level of the metabolic stress effector ATF4 is not affected by eIF2α O-GlcNAcylation under these conditions. 37217939 0 17 theme oxygenase 77:85 arg1 translation 89:99 heme oxygenase 1 translation 72:99 heme oxygenase 1 translation 72:99 Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis. 37217939 2 18 theme heme 266:269 arg1 oxygenase 271:279 the enzyme heme oxygenase 1 255:281 the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) 255:313 To combat this stress, the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) is thought to play a key role as an antioxidant. 37217939 1 19 theme metabolic 173:181 arg1 stress 183:188 metabolic stress 173:188 metabolic stress 173:188 BACKGROUND Nutrient limitations often lead to metabolic stress during cancer initiation and progression. 37217939 10 20 theme eIF2α 1486:1490 arg1 O-GlcNAcylation 1467:1481 O-GlcNAcylation 1467:1481 O-GlcNAcylation of eIF2α 1467:1490 We found that O-GlcNAcylation of eIF2α plays a crucial role in regulating antioxidant defense by suppressing the translation of the enzyme HO-1 during Arg limitation. 37217939 4 21 theme translation 685:695 arg1 factors 708:714 eukaryote translation initiation factors 675:714 eukaryote translation initiation factors (eIFs) 675:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 21 theme translation 685:695 arg1 eIFs 717:720 eIFs 717:720 eIFs 717:720 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 9 22 from targets 1422:1428 arg1 absence 1437:1443 the absence 1433:1443 the absence of Arg 1433:1450 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 13 23 theme metabolic 1965:1973 arg1 ATF4 1991:1994 the metabolic stress effector ATF4 1961:1994 the metabolic stress effector ATF4 1961:1994 However, the level of the metabolic stress effector ATF4 is not affected by eIF2α O-GlcNAcylation under these conditions. 37217939 0 24 theme cellular 105:112 arg1 homeostasis 114:124 cellular homeostasis 105:124 cellular homeostasis 105:124 Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis. 37217939 14 25 theme antioxidant 2182:2192 arg1 defense 2194:2200 antioxidant defense 2182:2200 antioxidant defense 2182:2200 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 14 26 theme initiation 2167:2176 arg1 control 2144:2150 the control 2140:2150 the control of translation initiation and antioxidant defense 2140:2200 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 5 27 theme extracellular 806:818 arg1 ArgS 839:842 ArgS 839:842 ArgS 839:842 The mechanism by which eIF2α O-GlcNAcylation regulates translation of HO-1 during extracellular arginine shortage (ArgS) remains unclear. 37217939 5 27 theme extracellular 806:818 arg1 shortage 829:836 extracellular arginine shortage 806:836 extracellular arginine shortage (ArgS) 806:843 The mechanism by which eIF2α O-GlcNAcylation regulates translation of HO-1 during extracellular arginine shortage (ArgS) remains unclear. 37217939 14 28 dep potential 2243:2251 arg1 biological 2253:2262 biological 2253:2262 biological 2253:2262 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 8 29 from migration 1204:1212 arg1 recovery 1194:1201 cell recovery 1189:1201 cell recovery 1189:1201 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 1 30 theme BACKGROUND 127:136 arg1 limitations 147:157 BACKGROUND Nutrient limitations 127:157 BACKGROUND Nutrient limitations 127:157 BACKGROUND Nutrient limitations often lead to metabolic stress during cancer initiation and progression. 37217939 9 31 dep RESULTS 1342:1348 arg1 identified 1363:1372 identified 1363:1372 identified 1363:1372 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 3 32 theme HO-1 417:420 arg1 mRNA 422:425 HO-1 mRNA 417:425 HO-1 mRNA 417:425 However, there is a discrepancy between the level of HO-1 mRNA and its protein, particularly in cells under stress. 37217939 4 33 theme O-linked 480:487 arg1 modification 522:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 480:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) 480:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 33 theme O-linked 480:487 arg1 mechanism 609:617 a recently discovered cellular signaling mechanism 568:617 a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs) 568:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 11 34 theme HMOX1 1736:1740 arg1 transcription 1742:1754 HMOX1 transcription 1736:1754 HMOX1 transcription 1736:1754 Our study showed that O-GlcNAcylation of eIF2α at specific sites suppresses HO-1 translation despite high levels of HMOX1 transcription. 37217939 5 35 theme HO-1 794:797 arg1 translation 779:789 translation 779:789 translation of HO-1 779:797 The mechanism by which eIF2α O-GlcNAcylation regulates translation of HO-1 during extracellular arginine shortage (ArgS) remains unclear. 37217939 9 36 theme O-GlcNAcylation 1406:1420 arg1 eIF2γ 1392:1396 eIF2γ 1392:1396 eIF2γ 1392:1396 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 9 36 theme O-GlcNAcylation 1406:1420 arg1 eIF2α 1374:1378 eIF2α 1374:1378 eIF2α 1374:1378 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 9 36 theme O-GlcNAcylation 1406:1420 arg1 eIF2β 1381:1385 eIF2β 1381:1385 eIF2β 1381:1385 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 9 36 theme O-GlcNAcylation 1406:1420 arg1 targets 1422:1428 key O-GlcNAcylation targets 1402:1428 key O-GlcNAcylation targets in the absence of Arg 1402:1450 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 6 37 dep METHODS 862:868 arg1 used 873:876 used 873:876 used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells 873:995 METHODS We used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells. 37217939 3 38 theme protein 435:441 arg1 level 408:412 the level 404:412 the level of HO-1 mRNA and its protein 404:441 However, there is a discrepancy between the level of HO-1 mRNA and its protein, particularly in cells under stress. 37217939 12 39 theme HO-1 1921:1924 arg1 translation 1926:1936 HO-1 translation 1921:1936 HO-1 translation 1921:1936 We also found that eliminating eIF2α O-GlcNAcylation through site-specific mutagenesis improves cell recovery, migration, and reduces ROS accumulation by restoring HO-1 translation. 37217939 8 40 from accumulation 1215:1226 arg1 recovery 1194:1201 cell recovery 1189:1201 cell recovery 1189:1201 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 10 41 theme HO-1 1592:1595 arg1 translation 1566:1576 the translation 1562:1576 the translation of the enzyme HO-1 1562:1595 We found that O-GlcNAcylation of eIF2α plays a crucial role in regulating antioxidant defense by suppressing the translation of the enzyme HO-1 during Arg limitation. 37217939 8 42 theme cell 1189:1192 arg1 recovery 1194:1201 cell recovery 1189:1201 cell recovery 1189:1201 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 4 43 theme discovered 579:588 arg1 modification 522:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 480:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) 480:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 43 theme discovered 579:588 arg1 mechanism 609:617 a recently discovered cellular signaling mechanism 568:617 a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs) 568:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 11 44 theme HO-1 1696:1699 arg1 translation 1701:1711 HO-1 translation 1696:1711 HO-1 translation 1696:1711 Our study showed that O-GlcNAcylation of eIF2α at specific sites suppresses HO-1 translation despite high levels of HMOX1 transcription. 37217939 9 45 theme Arg 1448:1450 arg1 absence 1437:1443 the absence 1433:1443 the absence of Arg 1433:1450 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 14 46 contain has 2239:2241 arg2 implications 2277:2288 potential biological and clinical implications 2243:2288 potential biological and clinical implications 2243:2288 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 14 46 contain has 2239:2241 arg1 O-GlcNAcylation 2216:2230 eIF2α O-GlcNAcylation 2210:2230 eIF2α O-GlcNAcylation 2210:2230 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 7 47 dep mutagenesis 1055:1065 arg1 labeling 1122:1129 N-azidoacetylglucosamine-tetraacylated labeling 1083:1129 N-azidoacetylglucosamine-tetraacylated labeling 1083:1129 We validated eIF2α O-GlcNAcylation through site-specific mutagenesis and azido sugar N-azidoacetylglucosamine-tetraacylated labeling. 37217939 14 48 dep CONCLUSIONS 2061:2071 arg1 provides 2093:2100 provides 2093:2100 provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications 2093:2288 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 12 49 theme cell 1853:1856 arg1 migration 1868:1876 migration 1868:1876 migration 1868:1876 We also found that eliminating eIF2α O-GlcNAcylation through site-specific mutagenesis improves cell recovery, migration, and reduces ROS accumulation by restoring HO-1 translation. 37217939 12 49 theme cell 1853:1856 arg1 recovery 1858:1865 cell recovery 1853:1865 cell recovery 1853:1865 We also found that eliminating eIF2α O-GlcNAcylation through site-specific mutagenesis improves cell recovery, migration, and reduces ROS accumulation by restoring HO-1 translation. 37217939 10 50 theme Arg 1604:1606 arg1 limitation 1608:1617 Arg limitation 1604:1617 Arg limitation 1604:1617 We found that O-GlcNAcylation of eIF2α plays a crucial role in regulating antioxidant defense by suppressing the translation of the enzyme HO-1 during Arg limitation. 37217939 1 51 theme cancer 197:202 arg1 initiation 204:213 cancer initiation 197:213 cancer initiation 197:213 BACKGROUND Nutrient limitations often lead to metabolic stress during cancer initiation and progression. 37217939 4 52 mod modification 522:533 arg3 β-N-acetylglucosamine 489:509 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 480:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) 480:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 52 mod modification 522:533 arg3 O-GlcNAc 512:519 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 480:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) 480:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 52 mod modification 522:533 arg1 O-GlcNAcylation 548:562 O-GlcNAcylation 548:562 O-GlcNAcylation 548:562 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 52 mod modification 522:533 arg1 proteins 538:545 proteins 538:545 proteins (O-GlcNAcylation) 538:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 6 53 theme mass 878:881 arg1 spectrometry 883:894 mass spectrometry 878:894 mass spectrometry 878:894 METHODS We used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells. 37217939 12 54 theme eIF2α 1788:1792 arg1 O-GlcNAcylation 1794:1808 eIF2α O-GlcNAcylation 1788:1808 eIF2α O-GlcNAcylation 1788:1808 We also found that eliminating eIF2α O-GlcNAcylation through site-specific mutagenesis improves cell recovery, migration, and reduces ROS accumulation by restoring HO-1 translation. 37217939 4 55 from phosphorylation 631:645 arg1 factors 708:714 eukaryote translation initiation factors 675:714 eukaryote translation initiation factors (eIFs) 675:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 55 from phosphorylation 631:645 arg1 proteins 655:662 many proteins 650:662 many proteins 650:662 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 8 56 theme oxygen 1240:1245 arg1 ROS 1256:1258 ROS 1256:1258 ROS 1256:1258 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 8 56 theme oxygen 1240:1245 arg1 species 1247:1253 reactive oxygen species 1231:1253 reactive oxygen species (ROS) 1231:1259 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 4 57 theme many 650:653 arg1 factors 708:714 eukaryote translation initiation factors 675:714 eukaryote translation initiation factors (eIFs) 675:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 57 theme many 650:653 arg1 proteins 655:662 many proteins 650:662 many proteins 650:662 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 6 58 theme breast 970:975 arg1 cells 991:995 breast cancer BT-549 cells 970:995 breast cancer BT-549 cells 970:995 METHODS We used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells. 37217939 4 59 theme signaling 599:607 arg1 modification 522:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 480:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) 480:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 59 theme signaling 599:607 arg1 mechanism 609:617 a recently discovered cellular signaling mechanism 568:617 a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs) 568:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 14 60 theme potential 2243:2251 arg1 implications 2277:2288 potential biological and clinical implications 2243:2288 potential biological and clinical implications 2243:2288 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 7 61 theme N-azidoacetylglucosamine-tetraacylated 1083:1120 arg1 labeling 1122:1129 N-azidoacetylglucosamine-tetraacylated labeling 1083:1129 N-azidoacetylglucosamine-tetraacylated labeling 1083:1129 We validated eIF2α O-GlcNAcylation through site-specific mutagenesis and azido sugar N-azidoacetylglucosamine-tetraacylated labeling. 37217939 2 62 theme enzyme 259:264 arg1 oxygenase 271:279 the enzyme heme oxygenase 1 255:281 the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) 255:313 To combat this stress, the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) is thought to play a key role as an antioxidant. 37217939 8 63 theme protein 1292:1298 arg1 synthesis 1300:1308 protein synthesis 1292:1308 protein synthesis 1292:1308 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 8 64 theme Arg 1326:1328 arg1 conditions 1330:1339 different Arg conditions 1316:1339 different Arg conditions 1316:1339 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 7 65 theme azido 1071:1075 arg1 sugar 1077:1081 azido sugar 1071:1081 azido sugar 1071:1081 We validated eIF2α O-GlcNAcylation through site-specific mutagenesis and azido sugar N-azidoacetylglucosamine-tetraacylated labeling. 37217939 7 66 theme site-specific 1041:1053 arg1 mutagenesis 1055:1065 site-specific mutagenesis 1041:1065 site-specific mutagenesis 1041:1065 We validated eIF2α O-GlcNAcylation through site-specific mutagenesis and azido sugar N-azidoacetylglucosamine-tetraacylated labeling. 37217939 1 67 theme Nutrient 138:145 arg1 limitations 147:157 BACKGROUND Nutrient limitations 127:157 BACKGROUND Nutrient limitations 127:157 BACKGROUND Nutrient limitations often lead to metabolic stress during cancer initiation and progression. 37217939 4 68 theme initiation 697:706 arg1 factors 708:714 eukaryote translation initiation factors 675:714 eukaryote translation initiation factors (eIFs) 675:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 68 theme initiation 697:706 arg1 eIFs 717:720 eIFs 717:720 eIFs 717:720 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 13 69 theme stress 1975:1980 arg1 ATF4 1991:1994 the metabolic stress effector ATF4 1961:1994 the metabolic stress effector ATF4 1961:1994 However, the level of the metabolic stress effector ATF4 is not affected by eIF2α O-GlcNAcylation under these conditions. 37217939 8 70 from labeling 1276:1283 arg1 recovery 1194:1201 cell recovery 1189:1201 cell recovery 1189:1201 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 8 71 from effect 1154:1159 arg1 recovery 1194:1201 cell recovery 1189:1201 cell recovery 1189:1201 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 13 72 theme ATF4 1991:1994 arg1 level 1952:1956 the level 1948:1956 the level of the metabolic stress effector ATF4 1948:1994 However, the level of the metabolic stress effector ATF4 is not affected by eIF2α O-GlcNAcylation under these conditions. 37217939 6 73 used used 873:876 arg2 We 870:871 We 870:871 We 870:871 METHODS We used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells. 37217939 5 74 theme eIF2α 747:751 arg1 O-GlcNAcylation 753:767 eIF2α O-GlcNAcylation 747:767 eIF2α O-GlcNAcylation 747:767 The mechanism by which eIF2α O-GlcNAcylation regulates translation of HO-1 during extracellular arginine shortage (ArgS) remains unclear. 37217939 8 75 theme O-GlcNAcylation 1170:1184 arg1 migration 1204:1212 migration 1204:1212 migration 1204:1212 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 8 75 theme O-GlcNAcylation 1170:1184 arg1 accumulation 1215:1226 accumulation 1215:1226 accumulation of reactive oxygen species (ROS) 1215:1259 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 8 75 theme O-GlcNAcylation 1170:1184 arg1 labeling 1276:1283 metabolic labeling 1266:1283 metabolic labeling during protein synthesis 1266:1308 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 8 75 theme O-GlcNAcylation 1170:1184 arg1 effect 1154:1159 the effect 1150:1159 the effect of eIF2α O-GlcNAcylation on cell recovery 1150:1201 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 14 76 theme eIF2α 2210:2214 arg1 O-GlcNAcylation 2216:2230 eIF2α O-GlcNAcylation 2210:2230 eIF2α O-GlcNAcylation 2210:2230 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 4 77 theme eukaryote 675:683 arg1 factors 708:714 eukaryote translation initiation factors 675:714 eukaryote translation initiation factors (eIFs) 675:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 77 theme eukaryote 675:683 arg1 eIFs 717:720 eIFs 717:720 eIFs 717:720 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 14 78 theme new 2102:2104 arg1 insights 2106:2113 new insights 2102:2113 new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications 2102:2288 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 14 79 theme defense 2194:2200 arg1 control 2144:2150 the control 2140:2150 the control of translation initiation and antioxidant defense 2140:2200 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 10 80 theme crucial 1500:1506 arg1 role 1508:1511 a crucial role 1498:1511 a crucial role 1498:1511 We found that O-GlcNAcylation of eIF2α plays a crucial role in regulating antioxidant defense by suppressing the translation of the enzyme HO-1 during Arg limitation. 37217939 0 81 theme arginine 14:21 arg1 availability 23:34 Extracellular arginine availability 0:34 Extracellular arginine availability 0:34 Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis. 37217939 14 82 theme translation 2155:2165 arg1 initiation 2167:2176 translation initiation 2155:2176 translation initiation 2155:2176 CONCLUSIONS Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications. 37217939 5 83 theme arginine 820:827 arg1 ArgS 839:842 ArgS 839:842 ArgS 839:842 The mechanism by which eIF2α O-GlcNAcylation regulates translation of HO-1 during extracellular arginine shortage (ArgS) remains unclear. 37217939 5 83 theme arginine 820:827 arg1 shortage 829:836 extracellular arginine shortage 806:836 extracellular arginine shortage (ArgS) 806:843 The mechanism by which eIF2α O-GlcNAcylation regulates translation of HO-1 during extracellular arginine shortage (ArgS) remains unclear. 37217939 4 84 theme proteins 538:545 arg1 modification 522:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 480:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) 480:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 84 theme proteins 538:545 arg1 mechanism 609:617 a recently discovered cellular signaling mechanism 568:617 a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs) 568:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 10 85 theme antioxidant 1527:1537 arg1 defense 1539:1545 antioxidant defense 1527:1545 antioxidant defense 1527:1545 We found that O-GlcNAcylation of eIF2α plays a crucial role in regulating antioxidant defense by suppressing the translation of the enzyme HO-1 during Arg limitation. 37217939 11 86 theme transcription 1742:1754 arg1 levels 1726:1731 high levels 1721:1731 high levels of HMOX1 transcription 1721:1754 Our study showed that O-GlcNAcylation of eIF2α at specific sites suppresses HO-1 translation despite high levels of HMOX1 transcription. 37217939 11 87 from sites 1679:1683 arg1 O-GlcNAcylation 1642:1656 O-GlcNAcylation 1642:1656 O-GlcNAcylation of eIF2α at specific sites 1642:1683 Our study showed that O-GlcNAcylation of eIF2α at specific sites suppresses HO-1 translation despite high levels of HMOX1 transcription. 37217939 4 88 theme β-N-acetylglucosamine 489:509 arg1 modification 522:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 480:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) 480:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 88 theme β-N-acetylglucosamine 489:509 arg1 mechanism 609:617 a recently discovered cellular signaling mechanism 568:617 a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs) 568:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 3 89 theme mRNA 422:425 arg1 level 408:412 the level 404:412 the level of HO-1 mRNA and its protein 404:441 However, there is a discrepancy between the level of HO-1 mRNA and its protein, particularly in cells under stress. 37217939 0 90 theme heme 72:75 arg1 oxygenase 77:85 heme oxygenase 1 72:87 heme oxygenase 1 translation 72:99 Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis. 37217939 9 91 theme key 1402:1404 arg1 eIF2γ 1392:1396 eIF2γ 1392:1396 eIF2γ 1392:1396 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 9 91 theme key 1402:1404 arg1 eIF2α 1374:1378 eIF2α 1374:1378 eIF2α 1374:1378 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 9 91 theme key 1402:1404 arg1 eIF2β 1381:1385 eIF2β 1381:1385 eIF2β 1381:1385 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 9 91 theme key 1402:1404 arg1 targets 1422:1428 key O-GlcNAcylation targets 1402:1428 key O-GlcNAcylation targets in the absence of Arg 1402:1450 RESULTS Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. 37217939 8 92 theme eIF2α 1164:1168 arg1 O-GlcNAcylation 1170:1184 eIF2α O-GlcNAcylation 1164:1184 eIF2α O-GlcNAcylation 1164:1184 We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. 37217939 4 93 theme O-GlcNAc 512:519 arg1 modification 522:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 480:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) 480:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 93 theme O-GlcNAc 512:519 arg1 mechanism 609:617 a recently discovered cellular signaling mechanism 568:617 a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs) 568:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 12 94 theme ROS 1891:1893 arg1 accumulation 1895:1906 ROS accumulation 1891:1906 ROS accumulation 1891:1906 We also found that eliminating eIF2α O-GlcNAcylation through site-specific mutagenesis improves cell recovery, migration, and reduces ROS accumulation by restoring HO-1 translation. 37217939 11 95 theme eIF2α 1661:1665 arg1 O-GlcNAcylation 1642:1656 O-GlcNAcylation 1642:1656 O-GlcNAcylation of eIF2α at specific sites 1642:1683 Our study showed that O-GlcNAcylation of eIF2α at specific sites suppresses HO-1 translation despite high levels of HMOX1 transcription. 37217939 4 96 theme cellular 590:597 arg1 modification 522:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification 480:533 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) 480:563 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 4 96 theme cellular 590:597 arg1 mechanism 609:617 a recently discovered cellular signaling mechanism 568:617 a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs) 568:721 O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). 37217939 10 97 theme enzyme 1585:1590 arg1 HO-1 1592:1595 the enzyme HO-1 1581:1595 the enzyme HO-1 1581:1595 We found that O-GlcNAcylation of eIF2α plays a crucial role in regulating antioxidant defense by suppressing the translation of the enzyme HO-1 during Arg limitation. 37086786 0 0 theme colorectal 81:90 arg1 tumorigenesis 99:111 colorectal cancer tumorigenesis 81:111 colorectal cancer tumorigenesis 81:111 O-GlcNAcylation promotes the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis. 37086786 9 1 theme hydrogen 1404:1411 arg1 bonding 1413:1419 hydrogen bonding 1404:1419 hydrogen bonding 1404:1419 Molecular dynamics simulations suggest that O-GlcNAcylation at S197 promotes the binding between the nuclear export signal motif and Crm1 through increasing hydrogen bonding. 37086786 1 2 with crosstalk 260:268 arg1 ubiquitination 295:308 ubiquitination 295:308 ubiquitination 295:308 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 1 2 with crosstalk 260:268 arg1 phosphorylation 275:289 phosphorylation 275:289 phosphorylation 275:289 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 1 3 theme emerging 160:167 arg1 modification 186:197 an emerging post-translation modification 157:197 an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes 157:352 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 1 3 theme emerging 160:167 arg1 N-acetylglucosamine 123:141 O-linked N-acetylglucosamine 114:141 O-linked N-acetylglucosamine (O-GlcNAc) 114:152 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 12 4 theme colorectal 1744:1753 arg1 tumorigenesis 1762:1774 colorectal cancer tumorigenesis 1744:1774 colorectal cancer tumorigenesis 1744:1774 We propose that the OGT-YTHDF1-c-Myc axis underlies colorectal cancer tumorigenesis. 37086786 8 5 theme cytosolic 1126:1134 arg1 portion 1136:1142 the cytosolic portion 1122:1142 the cytosolic portion of YTHDF1 1122:1152 Furthermore, O-GlcNAcylation increases the cytosolic portion of YTHDF1 by enhancing binding with Crm1, thus upregulating downstream target (e.g. c-Myc) expression. 37086786 11 6 theme O-GlcNAc 1669:1676 arg1 modification 1678:1689 O-GlcNAc modification 1669:1689 O-GlcNAc modification 1669:1689 In sum, we found that YTHDF1 is a nucleocytoplasmic protein, whose cytosolic localization is dependent on O-GlcNAc modification. 37086786 1 7 theme post-translation 169:184 arg1 modification 186:197 an emerging post-translation modification 157:197 an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes 157:352 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 1 7 theme post-translation 169:184 arg1 N-acetylglucosamine 123:141 O-linked N-acetylglucosamine 114:141 O-linked N-acetylglucosamine (O-GlcNAc) 114:152 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 0 8 theme tumorigenesis 99:111 arg1 localization 39:50 the cytosolic localization 25:50 the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis 25:111 O-GlcNAcylation promotes the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis. 37086786 8 9 theme YTHDF1 1147:1152 arg1 portion 1136:1142 the cytosolic portion 1122:1142 the cytosolic portion of YTHDF1 1122:1152 Furthermore, O-GlcNAcylation increases the cytosolic portion of YTHDF1 by enhancing binding with Crm1, thus upregulating downstream target (e.g. c-Myc) expression. 37086786 2 10 from involvement 385:395 arg1 regulation 451:460 N6-methyladenosine (m6A) regulation 426:460 N6-methyladenosine (m6A) regulation 426:460 The mechanisms underlying the involvement of O-GlcNAc modifications in N6-methyladenosine (m6A) regulation are not fully characterized. 37086786 3 11 theme protein 613:619 arg1 Crm1 621:624 the exportin protein Crm1 600:624 the exportin protein Crm1 600:624 Herein we show that O-GlcNAc modifies the m6A mRNA reader YTHDF1 and fine-tunes its nuclear translocation by the exportin protein Crm1. 37086786 11 12 theme cytosolic 1630:1638 arg1 localization 1640:1651 localization 1640:1651 localization 1640:1651 In sum, we found that YTHDF1 is a nucleocytoplasmic protein, whose cytosolic localization is dependent on O-GlcNAc modification. 37086786 0 13 theme cancer 92:97 arg1 tumorigenesis 99:111 colorectal cancer tumorigenesis 81:111 colorectal cancer tumorigenesis 81:111 O-GlcNAcylation promotes the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis. 37086786 7 14 theme nuclear 1047:1053 arg1 export 1055:1060 export 1055:1060 export 1055:1060 Moreover, we revealed that YTHDF1 is a nucleocytoplasmic protein, whose nuclear export is mediated by Crm1. 37086786 2 15 theme N6-methyladenosine 426:443 arg1 regulation 451:460 N6-methyladenosine (m6A) regulation 426:460 N6-methyladenosine (m6A) regulation 426:460 The mechanisms underlying the involvement of O-GlcNAc modifications in N6-methyladenosine (m6A) regulation are not fully characterized. 37086786 3 16 theme mRNA 537:540 arg1 YTHDF1 549:554 the m6A mRNA reader YTHDF1 529:554 the m6A mRNA reader YTHDF1 529:554 Herein we show that O-GlcNAc modifies the m6A mRNA reader YTHDF1 and fine-tunes its nuclear translocation by the exportin protein Crm1. 37086786 5 17 theme numerous 811:818 arg1 studies 835:841 numerous chemoproteomic studies 811:841 numerous chemoproteomic studies 811:841 Second, we verified Ser196/Ser197/Ser198 as the YTHDF1 O-GlcNAcylation sites, as described in numerous chemoproteomic studies. 37086786 6 18 theme O-GlcNAc-deficient 868:885 arg1 mutant 918:923 the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant 864:923 the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant 864:923 Then we constructed the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant, which significantly attenuated O-GlcNAc signals. 37086786 3 19 theme exportin 604:611 arg1 Crm1 621:624 the exportin protein Crm1 600:624 the exportin protein Crm1 600:624 Herein we show that O-GlcNAc modifies the m6A mRNA reader YTHDF1 and fine-tunes its nuclear translocation by the exportin protein Crm1. 37086786 9 20 theme export 1356:1361 arg1 signal 1363:1368 the nuclear export signal 1344:1368 the nuclear export signal motif 1344:1374 Molecular dynamics simulations suggest that O-GlcNAcylation at S197 promotes the binding between the nuclear export signal motif and Crm1 through increasing hydrogen bonding. 37086786 5 21 theme chemoproteomic 820:833 arg1 studies 835:841 numerous chemoproteomic studies 811:841 numerous chemoproteomic studies 811:841 Second, we verified Ser196/Ser197/Ser198 as the YTHDF1 O-GlcNAcylation sites, as described in numerous chemoproteomic studies. 37086786 1 22 theme various 325:331 arg1 processes 344:352 various biological processes 325:352 various biological processes 325:352 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 8 23 dep c-Myc 1228:1232 arg1 e.g. 1223:1226 e.g. 1223:1226 e.g. 1223:1226 Furthermore, O-GlcNAcylation increases the cytosolic portion of YTHDF1 by enhancing binding with Crm1, thus upregulating downstream target (e.g. c-Myc) expression. 37086786 7 24 theme nucleocytoplasmic 1014:1030 arg1 YTHDF1 1002:1007 YTHDF1 1002:1007 YTHDF1 1002:1007 Moreover, we revealed that YTHDF1 is a nucleocytoplasmic protein, whose nuclear export is mediated by Crm1. 37086786 7 24 theme nucleocytoplasmic 1014:1030 arg1 protein 1032:1038 a nucleocytoplasmic protein 1012:1038 a nucleocytoplasmic protein 1012:1038 Moreover, we revealed that YTHDF1 is a nucleocytoplasmic protein, whose nuclear export is mediated by Crm1. 37086786 0 25 theme cytosolic 29:37 arg1 localization 39:50 the cytosolic localization 25:50 the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis 25:111 O-GlcNAcylation promotes the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis. 37086786 1 26 theme biological 333:342 arg1 processes 344:352 various biological processes 325:352 various biological processes 325:352 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 5 27 theme YTHDF1 765:770 arg1 sites 788:792 the YTHDF1 O-GlcNAcylation sites 761:792 the YTHDF1 O-GlcNAcylation sites 761:792 Second, we verified Ser196/Ser197/Ser198 as the YTHDF1 O-GlcNAcylation sites, as described in numerous chemoproteomic studies. 37086786 5 27 theme YTHDF1 765:770 arg1 Ser196/Ser197/Ser198 737:756 Ser196/Ser197/Ser198 737:756 Ser196/Ser197/Ser198 737:756 Second, we verified Ser196/Ser197/Ser198 as the YTHDF1 O-GlcNAcylation sites, as described in numerous chemoproteomic studies. 37086786 6 28 theme YTHDF1-S196A/S197F/S198A 887:910 arg1 mutant 918:923 the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant 864:923 the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant 864:923 Then we constructed the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant, which significantly attenuated O-GlcNAc signals. 37086786 8 29 with binding 1167:1173 arg1 Crm1 1180:1183 Crm1 1180:1183 Crm1 1180:1183 Furthermore, O-GlcNAcylation increases the cytosolic portion of YTHDF1 by enhancing binding with Crm1, thus upregulating downstream target (e.g. c-Myc) expression. 37086786 3 30 theme m6A 533:535 arg1 YTHDF1 549:554 the m6A mRNA reader YTHDF1 529:554 the m6A mRNA reader YTHDF1 529:554 Herein we show that O-GlcNAc modifies the m6A mRNA reader YTHDF1 and fine-tunes its nuclear translocation by the exportin protein Crm1. 37086786 10 31 theme colon 1503:1507 arg1 cancer 1509:1514 the colon cancer mass and size 1499:1528 the colon cancer mass and size 1499:1528 Mouse xenograft assays further demonstrate that YTHDF1-AFA mutants decreased the colon cancer mass and size via decreasing c-Myc expression. 37086786 5 32 theme O-GlcNAcylation 772:786 arg1 sites 788:792 the YTHDF1 O-GlcNAcylation sites 761:792 the YTHDF1 O-GlcNAcylation sites 761:792 Second, we verified Ser196/Ser197/Ser198 as the YTHDF1 O-GlcNAcylation sites, as described in numerous chemoproteomic studies. 37086786 5 32 theme O-GlcNAcylation 772:786 arg1 Ser196/Ser197/Ser198 737:756 Ser196/Ser197/Ser198 737:756 Ser196/Ser197/Ser198 737:756 Second, we verified Ser196/Ser197/Ser198 as the YTHDF1 O-GlcNAcylation sites, as described in numerous chemoproteomic studies. 37086786 9 33 theme signal 1363:1368 arg1 motif 1370:1374 the nuclear export signal motif 1344:1374 the nuclear export signal motif 1344:1374 Molecular dynamics simulations suggest that O-GlcNAcylation at S197 promotes the binding between the nuclear export signal motif and Crm1 through increasing hydrogen bonding. 37086786 1 34 theme O-linked 114:121 arg1 O-GlcNAc 144:151 O-GlcNAc 144:151 O-GlcNAc 144:151 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 1 34 theme O-linked 114:121 arg1 N-acetylglucosamine 123:141 O-linked N-acetylglucosamine 114:141 O-linked N-acetylglucosamine (O-GlcNAc) 114:152 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 1 34 theme O-linked 114:121 arg1 modification 186:197 an emerging post-translation modification 157:197 an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes 157:352 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 10 35 theme xenograft 1428:1436 arg1 assays 1438:1443 Mouse xenograft assays 1422:1443 Mouse xenograft assays 1422:1443 Mouse xenograft assays further demonstrate that YTHDF1-AFA mutants decreased the colon cancer mass and size via decreasing c-Myc expression. 37086786 1 36 theme cellular 228:235 arg1 transduction 244:255 cellular signal transduction 228:255 cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes 228:352 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 9 37 theme nuclear 1348:1354 arg1 signal 1363:1368 the nuclear export signal 1344:1368 the nuclear export signal motif 1344:1374 Molecular dynamics simulations suggest that O-GlcNAcylation at S197 promotes the binding between the nuclear export signal motif and Crm1 through increasing hydrogen bonding. 37086786 10 38 theme Mouse 1422:1426 arg1 assays 1438:1443 Mouse xenograft assays 1422:1443 Mouse xenograft assays 1422:1443 Mouse xenograft assays further demonstrate that YTHDF1-AFA mutants decreased the colon cancer mass and size via decreasing c-Myc expression. 37086786 1 39 theme signal 237:242 arg1 transduction 244:255 cellular signal transduction 228:255 cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes 228:352 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 12 40 theme OGT-YTHDF1-c-Myc 1712:1727 arg1 axis 1729:1732 the OGT-YTHDF1-c-Myc axis 1708:1732 the OGT-YTHDF1-c-Myc axis 1708:1732 We propose that the OGT-YTHDF1-c-Myc axis underlies colorectal cancer tumorigenesis. 37086786 6 41 theme O-GlcNAc 957:964 arg1 signals 966:972 O-GlcNAc signals 957:972 O-GlcNAc signals 957:972 Then we constructed the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant, which significantly attenuated O-GlcNAc signals. 37086786 0 42 theme m6A 59:61 arg1 YTHDF1 70:75 the m6A reader YTHDF1 55:75 the m6A reader YTHDF1 55:75 O-GlcNAcylation promotes the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis. 37086786 8 43 theme target 1215:1220 arg1 expression 1235:1244 downstream target (e.g. c-Myc) expression 1204:1244 downstream target (e.g. c-Myc) expression 1204:1244 Furthermore, O-GlcNAcylation increases the cytosolic portion of YTHDF1 by enhancing binding with Crm1, thus upregulating downstream target (e.g. c-Myc) expression. 37086786 0 44 theme reader 63:68 arg1 YTHDF1 70:75 the m6A reader YTHDF1 55:75 the m6A reader YTHDF1 55:75 O-GlcNAcylation promotes the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis. 37086786 10 45 theme YTHDF1-AFA 1470:1479 arg1 mutants 1481:1487 YTHDF1-AFA mutants 1470:1487 YTHDF1-AFA mutants 1470:1487 Mouse xenograft assays further demonstrate that YTHDF1-AFA mutants decreased the colon cancer mass and size via decreasing c-Myc expression. 37086786 2 46 theme modifications 409:421 arg1 involvement 385:395 the involvement 381:395 the involvement of O-GlcNAc modifications in N6-methyladenosine (m6A) regulation 381:460 The mechanisms underlying the involvement of O-GlcNAc modifications in N6-methyladenosine (m6A) regulation are not fully characterized. 37086786 8 47 theme downstream 1204:1213 arg1 target 1215:1220 downstream target 1204:1220 downstream target (e.g. c-Myc) expression 1204:1244 Furthermore, O-GlcNAcylation increases the cytosolic portion of YTHDF1 by enhancing binding with Crm1, thus upregulating downstream target (e.g. c-Myc) expression. 37086786 10 48 theme c-Myc 1545:1549 arg1 expression 1551:1560 c-Myc expression 1545:1560 c-Myc expression 1545:1560 Mouse xenograft assays further demonstrate that YTHDF1-AFA mutants decreased the colon cancer mass and size via decreasing c-Myc expression. 37086786 3 49 theme nuclear 575:581 arg1 translocation 583:595 its nuclear translocation 571:595 its nuclear translocation by the exportin protein Crm1 571:624 Herein we show that O-GlcNAc modifies the m6A mRNA reader YTHDF1 and fine-tunes its nuclear translocation by the exportin protein Crm1. 37086786 2 50 theme O-GlcNAc 400:407 arg1 modifications 409:421 O-GlcNAc modifications 400:421 O-GlcNAc modifications 400:421 The mechanisms underlying the involvement of O-GlcNAc modifications in N6-methyladenosine (m6A) regulation are not fully characterized. 37086786 6 51 theme AFA 913:915 arg1 mutant 918:923 the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant 864:923 the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant 864:923 Then we constructed the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant, which significantly attenuated O-GlcNAc signals. 37086786 3 52 theme reader 542:547 arg1 YTHDF1 549:554 the m6A mRNA reader YTHDF1 529:554 the m6A mRNA reader YTHDF1 529:554 Herein we show that O-GlcNAc modifies the m6A mRNA reader YTHDF1 and fine-tunes its nuclear translocation by the exportin protein Crm1. 37086786 12 53 theme cancer 1755:1760 arg1 tumorigenesis 1762:1774 colorectal cancer tumorigenesis 1744:1774 colorectal cancer tumorigenesis 1744:1774 We propose that the OGT-YTHDF1-c-Myc axis underlies colorectal cancer tumorigenesis. 37086786 9 54 theme Molecular 1247:1255 arg1 simulations 1266:1276 Molecular dynamics simulations 1247:1276 Molecular dynamics simulations 1247:1276 Molecular dynamics simulations suggest that O-GlcNAcylation at S197 promotes the binding between the nuclear export signal motif and Crm1 through increasing hydrogen bonding. 37086786 10 55 dep cancer 1509:1514 arg1 size 1525:1528 size 1525:1528 size 1525:1528 Mouse xenograft assays further demonstrate that YTHDF1-AFA mutants decreased the colon cancer mass and size via decreasing c-Myc expression. 37086786 10 55 dep cancer 1509:1514 arg1 mass 1516:1519 mass 1516:1519 mass 1516:1519 Mouse xenograft assays further demonstrate that YTHDF1-AFA mutants decreased the colon cancer mass and size via decreasing c-Myc expression. 37086786 0 56 theme YTHDF1 70:75 arg1 localization 39:50 the cytosolic localization 25:50 the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis 25:111 O-GlcNAcylation promotes the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis. 37086786 9 57 theme dynamics 1257:1264 arg1 simulations 1266:1276 Molecular dynamics simulations 1247:1276 Molecular dynamics simulations 1247:1276 Molecular dynamics simulations suggest that O-GlcNAcylation at S197 promotes the binding between the nuclear export signal motif and Crm1 through increasing hydrogen bonding. 37086786 11 58 theme nucleocytoplasmic 1597:1613 arg1 protein 1615:1621 a nucleocytoplasmic protein 1595:1621 a nucleocytoplasmic protein 1595:1621 In sum, we found that YTHDF1 is a nucleocytoplasmic protein, whose cytosolic localization is dependent on O-GlcNAc modification. 37086786 11 58 theme nucleocytoplasmic 1597:1613 arg1 YTHDF1 1585:1590 YTHDF1 1585:1590 YTHDF1 1585:1590 In sum, we found that YTHDF1 is a nucleocytoplasmic protein, whose cytosolic localization is dependent on O-GlcNAc modification. 37086786 4 59 theme O-GlcNAc 689:696 arg1 OGT 711:713 OGT 711:713 OGT 711:713 First we present evidence that YTHDF1 interacts with the sole O-GlcNAc transferase (OGT). 37086786 4 59 theme O-GlcNAc 689:696 arg1 transferase 698:708 sole O-GlcNAc transferase 684:708 the sole O-GlcNAc transferase (OGT) 680:714 First we present evidence that YTHDF1 interacts with the sole O-GlcNAc transferase (OGT). 37086786 1 60 link O-linked 114:121 arg1 O-GlcNAc 144:151 O-GlcNAc 144:151 O-GlcNAc 144:151 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 1 60 link O-linked 114:121 arg1 N-acetylglucosamine 123:141 O-linked N-acetylglucosamine 114:141 O-linked N-acetylglucosamine (O-GlcNAc) 114:152 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 1 60 link O-linked 114:121 arg1 modification 186:197 an emerging post-translation modification 157:197 an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes 157:352 O-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. 37086786 9 61 from S197 1310:1313 arg1 O-GlcNAcylation 1291:1305 O-GlcNAcylation 1291:1305 O-GlcNAcylation at S197 1291:1313 Molecular dynamics simulations suggest that O-GlcNAcylation at S197 promotes the binding between the nuclear export signal motif and Crm1 through increasing hydrogen bonding. 37086786 4 62 theme sole 684:687 arg1 OGT 711:713 OGT 711:713 OGT 711:713 First we present evidence that YTHDF1 interacts with the sole O-GlcNAc transferase (OGT). 37086786 4 62 theme sole 684:687 arg1 transferase 698:708 sole O-GlcNAc transferase 684:708 the sole O-GlcNAc transferase (OGT) 680:714 First we present evidence that YTHDF1 interacts with the sole O-GlcNAc transferase (OGT). 36240740 4 0 theme antiparallel 472:483 arg1 bundle 485:490 an antiparallel bundle 469:490 an antiparallel bundle 469:490 In the complex, four Unc5D molecules pack into an antiparallel bundle, flanked by four GPC3 molecules. 36240740 3 1 gly glycoprotein 400:411 arg1 glycoprotein 400:411 an octameric glycoprotein complex 387:419 an octameric glycoprotein complex 387:419 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 5 2 theme thrombospondin-like 671:689 arg1 domains 691:697 the Unc5D thrombospondin-like domains 661:697 the Unc5D thrombospondin-like domains 661:697 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 8 3 theme Unc5-GPC3 1127:1135 arg1 interactions 1137:1148 finely balanced Unc5-GPC3 interactions 1111:1148 finely balanced Unc5-GPC3 interactions 1111:1148 The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration. 36240740 8 4 theme guidance 1095:1102 arg1 mechanism 1077:1085 a conserved structural mechanism 1054:1085 a conserved structural mechanism 1054:1085 The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration. 36240740 8 5 theme cell 1090:1093 arg1 guidance 1095:1102 cell guidance 1090:1102 cell guidance 1090:1102 The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration. 36240740 7 6 theme cancer 970:975 arg1 cells 977:981 cancer cells 970:981 cancer cells 970:981 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 7 7 from cells 977:981 arg1 cortex 958:963 the mouse cortex 948:963 the mouse cortex 948:963 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 3 8 theme receptor 351:358 arg1 GPC3 372:375 GPC3 372:375 GPC3 372:375 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 3 8 theme receptor 351:358 arg1 glypican-3 360:369 morphogen receptor glypican-3 341:369 morphogen receptor glypican-3 (GPC3) 341:376 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 5 9 theme C-mannosylated 631:644 arg1 tryptophans 646:656 C-mannosylated tryptophans 631:656 C-mannosylated tryptophans of the Unc5D thrombospondin-like domains 631:697 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 8 10 theme conserved 1056:1064 arg1 mechanism 1077:1085 a conserved structural mechanism 1054:1085 a conserved structural mechanism 1054:1085 The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration. 36240740 5 11 theme Central 525:531 arg1 interactions 547:558 Central glycan-glycan interactions 525:558 Central glycan-glycan interactions 525:558 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 6 12 theme crystallographic 775:790 arg1 data 792:795 the crystallographic data 771:795 the crystallographic data 771:795 MD simulations, mass spectrometry and structure-based mutants validate the crystallographic data. 36240740 7 13 theme mutant 874:879 arg1 proteins 881:888 mutant proteins 874:888 mutant proteins 874:888 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 1 14 theme Neural 65:70 arg1 migration 72:80 Neural migration 65:80 Neural migration 65:80 Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. 36240740 1 14 theme Neural 65:70 arg1 step 96:99 a critical step 85:99 a critical step during brain development that requires the interactions of cell-surface guidance receptors 85:190 Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. 36240740 6 15 theme MD 700:701 arg1 simulations 703:713 MD simulations 700:713 MD simulations 700:713 MD simulations, mass spectrometry and structure-based mutants validate the crystallographic data. 36240740 1 16 theme cell-surface 160:171 arg1 receptors 182:190 cell-surface guidance receptors 160:190 cell-surface guidance receptors 160:190 Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. 36240740 3 17 theme morphogen 341:349 arg1 GPC3 372:375 GPC3 372:375 GPC3 372:375 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 3 17 theme morphogen 341:349 arg1 glypican-3 360:369 morphogen receptor glypican-3 341:369 morphogen receptor glypican-3 (GPC3) 341:376 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 0 18 from role 41:44 arg1 migration 54:62 cell migration 49:62 cell migration 49:62 GPC3-Unc5 receptor complex structure and role in cell migration. 36240740 8 19 theme structural 1066:1075 arg1 mechanism 1077:1085 a conserved structural mechanism 1054:1085 a conserved structural mechanism 1054:1085 The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration. 36240740 7 20 theme mouse 952:956 arg1 cortex 958:963 the mouse cortex 948:963 the mouse cortex 948:963 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 1 21 theme guidance 173:180 arg1 receptors 182:190 cell-surface guidance receptors 160:190 cell-surface guidance receptors 160:190 Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. 36240740 0 22 theme receptor 10:17 arg1 structure 27:35 GPC3-Unc5 receptor complex structure 0:35 GPC3-Unc5 receptor complex structure 0:35 GPC3-Unc5 receptor complex structure and role in cell migration. 36240740 4 23 from pack 459:462 arg1 complex 429:435 the complex 425:435 the complex 425:435 In the complex, four Unc5D molecules pack into an antiparallel bundle, flanked by four GPC3 molecules. 36240740 8 24 theme balanced 1118:1125 arg1 interactions 1137:1148 finely balanced Unc5-GPC3 interactions 1111:1148 finely balanced Unc5-GPC3 interactions 1111:1148 The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration. 36240740 1 25 theme receptors 182:190 arg1 interactions 144:155 the interactions 140:155 the interactions of cell-surface guidance receptors 140:190 Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. 36240740 0 26 theme GPC3-Unc5 0:8 arg1 structure 27:35 GPC3-Unc5 receptor complex structure 0:35 GPC3-Unc5 receptor complex structure 0:35 GPC3-Unc5 receptor complex structure and role in cell migration. 36240740 5 27 gly C-mannosylated 631:644 arg1 tryptophans 646:656 C-mannosylated tryptophans 631:656 C-mannosylated tryptophans of the Unc5D thrombospondin-like domains 631:697 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 5 28 theme domains 691:697 arg1 tryptophans 646:656 C-mannosylated tryptophans 631:656 C-mannosylated tryptophans of the Unc5D thrombospondin-like domains 631:697 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 5 28 theme domains 691:697 arg1 GPC3 606:609 GPC3 606:609 GPC3 (N241 in human) 606:625 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 5 29 theme N-linked 574:581 arg1 glycans 583:589 N-linked glycans 574:589 N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains 574:697 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 1 30 theme critical 87:94 arg1 migration 72:80 Neural migration 65:80 Neural migration 65:80 Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. 36240740 1 30 theme critical 87:94 arg1 step 96:99 a critical step 85:99 a critical step during brain development that requires the interactions of cell-surface guidance receptors 85:190 Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. 36240740 0 31 theme complex 19:25 arg1 structure 27:35 GPC3-Unc5 receptor complex structure 0:35 GPC3-Unc5 receptor complex structure 0:35 GPC3-Unc5 receptor complex structure and role in cell migration. 36240740 7 32 theme neuroblastoma 1009:1021 arg1 model 1023:1027 an embryonic xenograft neuroblastoma model 986:1027 an embryonic xenograft neuroblastoma model 986:1027 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 7 33 from neurons 937:943 arg1 cortex 958:963 the mouse cortex 948:963 the mouse cortex 948:963 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 7 34 theme Unc5-GPC3 837:845 arg1 binding 847:853 Unc5-GPC3 binding 837:853 Unc5-GPC3 binding 837:853 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 3 35 theme octameric 390:398 arg1 complex 413:419 an octameric glycoprotein complex 387:419 an octameric glycoprotein complex 387:419 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 5 36 from N241 612:615 arg1 human 620:624 human 620:624 human 620:624 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 3 37 theme glycoprotein 400:411 arg1 complex 413:419 an octameric glycoprotein complex 387:419 an octameric glycoprotein complex 387:419 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 3 38 theme crystal 268:274 arg1 structures 276:285 crystal structures 268:285 crystal structures of Uncoordinated-5 receptor D (Unc5D) 268:323 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 4 39 theme Unc5D 443:447 arg1 molecules 449:457 four Unc5D molecules 438:457 four Unc5D molecules 438:457 In the complex, four Unc5D molecules pack into an antiparallel bundle, flanked by four GPC3 molecules. 36240740 0 40 theme cell 49:52 arg1 migration 54:62 cell migration 49:62 cell migration 49:62 GPC3-Unc5 receptor complex structure and role in cell migration. 36240740 3 41 theme D 315:315 arg1 structures 276:285 crystal structures 268:285 crystal structures of Uncoordinated-5 receptor D (Unc5D) 268:323 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 5 42 theme Unc5D 665:669 arg1 domains 691:697 the Unc5D thrombospondin-like domains 661:697 the Unc5D thrombospondin-like domains 661:697 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 7 43 dep nanobodies 808:817 arg1 enhance 819:825 enhance 819:825 enhance 819:825 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 7 43 dep nanobodies 808:817 arg1 show 891:894 show 891:894 show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model 891:1027 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 7 43 dep nanobodies 808:817 arg1 weaken 830:835 weaken 830:835 weaken Unc5-GPC3 binding 830:853 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 5 44 theme glycan-glycan 533:545 arg1 interactions 547:558 Central glycan-glycan interactions 525:558 Central glycan-glycan interactions 525:558 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 1 45 theme brain 108:112 arg1 development 114:124 brain development 108:124 brain development 108:124 Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. 36240740 7 46 theme pyramidal 927:935 arg1 neurons 937:943 pyramidal neurons 927:943 pyramidal neurons in the mouse cortex 927:963 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 4 47 theme GPC3 509:512 arg1 molecules 514:522 four GPC3 molecules 504:522 four GPC3 molecules 504:522 In the complex, four Unc5D molecules pack into an antiparallel bundle, flanked by four GPC3 molecules. 36240740 3 48 theme Uncoordinated-5 290:304 arg1 Unc5D 318:322 Unc5D 318:322 Unc5D 318:322 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 3 48 theme Uncoordinated-5 290:304 arg1 D 315:315 Uncoordinated-5 receptor D 290:315 Uncoordinated-5 receptor D (Unc5D) 290:323 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 6 49 theme structure-based 738:752 arg1 mutants 754:760 structure-based mutants 738:760 structure-based mutants 738:760 MD simulations, mass spectrometry and structure-based mutants validate the crystallographic data. 36240740 5 50 dep GPC3 606:609 arg1 N241 612:615 N241 612:615 N241 612:615 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 3 51 theme receptor 306:313 arg1 Unc5D 318:322 Unc5D 318:322 Unc5D 318:322 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 3 51 theme receptor 306:313 arg1 D 315:315 Uncoordinated-5 receptor D 290:315 Uncoordinated-5 receptor D (Unc5D) 290:323 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 7 52 theme embryonic 989:997 arg1 model 1023:1027 an embryonic xenograft neuroblastoma model 986:1027 an embryonic xenograft neuroblastoma model 986:1027 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 5 53 link N-linked 574:581 arg1 glycans 583:589 N-linked glycans 574:589 N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains 574:697 Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. 36240740 2 54 theme Cancer 193:198 arg1 cells 200:204 Cancer cells 193:204 Cancer cells 193:204 Cancer cells often hijack these mechanisms to disseminate. 36240740 7 55 theme xenograft 999:1007 arg1 model 1023:1027 an embryonic xenograft neuroblastoma model 986:1027 an embryonic xenograft neuroblastoma model 986:1027 Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. 36240740 8 56 theme cell 1159:1162 arg1 migration 1164:1172 cell migration 1159:1172 cell migration 1159:1172 The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration. 36240740 0 57 from structure 27:35 arg1 migration 54:62 cell migration 49:62 cell migration 49:62 GPC3-Unc5 receptor complex structure and role in cell migration. 36240740 3 58 with complex 328:334 arg1 GPC3 372:375 GPC3 372:375 GPC3 372:375 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 3 58 with complex 328:334 arg1 glypican-3 360:369 morphogen receptor glypican-3 341:369 morphogen receptor glypican-3 (GPC3) 341:376 Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. 36240740 6 59 theme mass 716:719 arg1 spectrometry 721:732 mass spectrometry 716:732 mass spectrometry 716:732 MD simulations, mass spectrometry and structure-based mutants validate the crystallographic data. 36214454 8 0 theme Pgm1 1271:1274 arg1 proteins 1283:1290 purified Pgm1 mutant proteins 1262:1290 purified Pgm1 mutant proteins 1262:1290 Finally, we characterize the enzymatic activity of purified Pgm1 mutant proteins. 36214454 10 1 theme experimental 1496:1507 arg1 evolution 1509:1517 experimental evolution 1496:1517 experimental evolution 1496:1517 Broadly, our results demonstrate the power of experimental evolution as a tool for identifying genes and pathways that compensate for human-disease-associated alleles. 36214454 6 2 theme compensatory 809:820 arg1 mutations 822:830 compensatory mutations 809:830 compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast 809:984 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 8 3 theme mutant 1276:1281 arg1 proteins 1283:1290 purified Pgm1 mutant proteins 1262:1290 purified Pgm1 mutant proteins 1262:1290 Finally, we characterize the enzymatic activity of purified Pgm1 mutant proteins. 36214454 1 4 theme protein 233:239 arg1 glycosylation 257:269 protein N-linked glycosylation 233:269 protein N-linked glycosylation 233:269 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 0 5 theme disease 78:84 arg1 models 62:67 yeast models 56:67 yeast models of human disease 56:84 Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease. 36214454 0 6 from rescue 13:18 arg1 models 62:67 yeast models 56:67 yeast models of human disease 56:84 Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease. 36214454 1 7 theme N-linked 241:255 arg1 glycosylation 257:269 protein N-linked glycosylation 233:269 protein N-linked glycosylation 233:269 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 8 8 theme proteins 1283:1290 arg1 activity 1250:1257 the enzymatic activity 1236:1257 the enzymatic activity of purified Pgm1 mutant proteins 1236:1290 Finally, we characterize the enzymatic activity of purified Pgm1 mutant proteins. 36214454 3 9 dep one 386:388 arg1 SEC53 487:498 SEC53 487:498 SEC53 487:498 We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. 36214454 6 10 theme CDG 895:897 arg1 Type 888:891 Type 1 CDG 888:897 Type 1 CDG 888:897 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 7 11 theme allele-specific 1074:1088 arg1 mutations 1047:1055 evolved pgm1 mutations 1027:1055 evolved pgm1 mutations 1027:1055 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 7 11 theme allele-specific 1074:1088 arg1 interactors 1098:1108 dominant and allele-specific genetic interactors 1061:1108 dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele 1061:1208 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 7 12 theme genetic 1090:1096 arg1 mutations 1047:1055 evolved pgm1 mutations 1027:1055 evolved pgm1 mutations 1027:1055 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 7 12 theme genetic 1090:1096 arg1 interactors 1098:1108 dominant and allele-specific genetic interactors 1061:1108 dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele 1061:1208 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 6 13 theme other 835:839 arg1 PGM1 910:920 PGM1 910:920 PGM1 910:920 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 6 13 theme other 835:839 arg1 genes 841:845 other genes 835:845 other genes 835:845 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 9 14 theme sec53-V238M 1423:1440 arg1 allele 1442:1447 the sec53-V238M allele 1419:1447 the sec53-V238M allele 1419:1447 We find that reduction, but not elimination, of Pgm1 activity best compensates for the deleterious phenotypes associated with the sec53-V238M allele. 36214454 7 15 theme protein 1128:1134 arg1 glycosylation 1136:1148 protein glycosylation 1128:1148 protein glycosylation 1128:1148 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 5 16 theme whole-genome 671:682 arg1 sequencing 684:693 whole-genome sequencing 671:693 whole-genome sequencing 671:693 Through whole-genome sequencing we identify compensatory mutations, including known SEC53 genetic interactors. 36214454 2 17 theme human 321:325 arg1 PMM2 327:337 human PMM2 321:337 human PMM2 321:337 The yeast gene SEC53 encodes a homolog of human PMM2. 36214454 1 18 link N-linked 241:255 arg1 glycosylation 257:269 protein N-linked glycosylation 233:269 protein N-linked glycosylation 233:269 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 2 19 theme yeast 276:280 arg1 gene 282:285 The yeast gene SEC53 272:298 The yeast gene SEC53 272:298 The yeast gene SEC53 encodes a homolog of human PMM2. 36214454 2 19 theme yeast 276:280 arg1 homolog 310:316 a homolog 308:316 a homolog of human PMM2 308:337 The yeast gene SEC53 encodes a homolog of human PMM2. 36214454 3 20 theme human-disease-associated 397:420 arg1 sec53-F126L 454:471 sec53-F126L 454:471 sec53-F126L 454:471 We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. 36214454 3 20 theme human-disease-associated 397:420 arg1 sec53-V238M 431:448 sec53-V238M 431:448 sec53-V238M 431:448 We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. 36214454 3 20 theme human-disease-associated 397:420 arg1 alleles 422:428 two human-disease-associated alleles 393:428 two human-disease-associated alleles 393:428 We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. 36214454 6 21 from enrichment 795:804 arg1 PGM1 910:920 PGM1 910:920 PGM1 910:920 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 6 21 from enrichment 795:804 arg1 genes 841:845 other genes 835:845 other genes 835:845 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 9 22 theme activity 1346:1353 arg1 reduction 1306:1314 reduction 1306:1314 reduction 1306:1314 We find that reduction, but not elimination, of Pgm1 activity best compensates for the deleterious phenotypes associated with the sec53-V238M allele. 36214454 7 23 theme pgm1 1035:1045 arg1 mutations 1047:1055 evolved pgm1 mutations 1027:1055 evolved pgm1 mutations 1027:1055 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 7 23 theme pgm1 1035:1045 arg1 interactors 1098:1108 dominant and allele-specific genetic interactors 1061:1108 dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele 1061:1208 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 6 24 theme phosphoglucomutase 958:975 arg1 PGM1 910:920 PGM1 910:920 PGM1 910:920 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 6 24 theme phosphoglucomutase 958:975 arg1 isoform 947:953 the minor isoform 937:953 the minor isoform of phosphoglucomutase in yeast 937:984 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 5 25 theme compensatory 707:718 arg1 mutations 720:728 compensatory mutations 707:728 compensatory mutations 707:728 Through whole-genome sequencing we identify compensatory mutations, including known SEC53 genetic interactors. 36214454 5 25 theme compensatory 707:718 arg1 interactors 768:778 known SEC53 genetic interactors 741:778 known SEC53 genetic interactors 741:778 Through whole-genome sequencing we identify compensatory mutations, including known SEC53 genetic interactors. 36214454 7 26 theme evolved 1027:1033 arg1 mutations 1047:1055 evolved pgm1 mutations 1027:1055 evolved pgm1 mutations 1027:1055 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 7 26 theme evolved 1027:1033 arg1 interactors 1098:1108 dominant and allele-specific genetic interactors 1061:1108 dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele 1061:1208 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 0 27 theme Evolutionary 0:11 arg1 rescue 13:18 Evolutionary rescue 0:18 Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease 0:84 Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease. 36214454 9 28 theme deleterious 1380:1390 arg1 phenotypes 1392:1401 the deleterious phenotypes 1376:1401 the deleterious phenotypes associated with the sec53-V238M allele 1376:1447 We find that reduction, but not elimination, of Pgm1 activity best compensates for the deleterious phenotypes associated with the sec53-V238M allele. 36214454 3 29 theme yeast 370:374 arg1 populations 355:365 384 populations 351:365 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53 351:498 We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. 36214454 4 30 theme slow-growth 574:584 arg1 phenotype 586:594 the slow-growth phenotype 570:594 the slow-growth phenotype associated with the sec53 human-disease-associated alleles 570:660 We find that after 1000 generations, most populations compensate for the slow-growth phenotype associated with the sec53 human-disease-associated alleles. 36214454 10 31 theme evolution 1509:1517 arg1 power 1487:1491 the power 1483:1491 the power of experimental evolution 1483:1517 Broadly, our results demonstrate the power of experimental evolution as a tool for identifying genes and pathways that compensate for human-disease-associated alleles. 36214454 10 31 theme evolution 1509:1517 arg1 tool 1524:1527 a tool 1522:1527 a tool for identifying genes and pathways that compensate for human-disease-associated alleles 1522:1615 Broadly, our results demonstrate the power of experimental evolution as a tool for identifying genes and pathways that compensate for human-disease-associated alleles. 36214454 1 32 theme common 96:101 arg1 mutations 166:174 mutations 166:174 mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation 166:269 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 1 32 theme common 96:101 arg1 cause 103:107 The most common cause 87:107 The most common cause of human congenital disorders of glycosylation (CDG) 87:160 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 10 33 theme human-disease-associated 1584:1607 arg1 alleles 1609:1615 human-disease-associated alleles 1584:1615 human-disease-associated alleles 1584:1615 Broadly, our results demonstrate the power of experimental evolution as a tool for identifying genes and pathways that compensate for human-disease-associated alleles. 36214454 6 34 from isoform 947:953 arg1 yeast 980:984 yeast 980:984 yeast 980:984 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 7 35 theme sec53-V238M 1184:1201 arg1 allele 1203:1208 the sec53-V238M allele 1180:1208 the sec53-V238M allele 1180:1208 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 8 36 theme purified 1262:1269 arg1 proteins 1283:1290 purified Pgm1 mutant proteins 1262:1290 purified Pgm1 mutant proteins 1262:1290 Finally, we characterize the enzymatic activity of purified Pgm1 mutant proteins. 36214454 1 37 theme phosphomannomutase 183:200 arg1 215:218 215:218 215:218 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 1 37 theme phosphomannomutase 183:200 arg1 PMM2 207:213 the phosphomannomutase gene PMM2 179:213 the phosphomannomutase gene PMM2 179:213 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 3 38 theme alleles 422:428 arg1 one 386:388 one 386:388 one 386:388 We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. 36214454 3 38 theme alleles 422:428 arg1 sec53-F126L 454:471 sec53-F126L 454:471 sec53-F126L 454:471 We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. 36214454 3 38 theme alleles 422:428 arg1 sec53-V238M 431:448 sec53-V238M 431:448 sec53-V238M 431:448 We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. 36214454 3 38 theme alleles 422:428 arg1 alleles 422:428 two human-disease-associated alleles 393:428 two human-disease-associated alleles 393:428 We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. 36214454 6 39 from genes 841:845 arg1 enrichment 795:804 an enrichment 792:804 an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast 792:984 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 7 40 theme yeast 1164:1168 arg1 growth 1154:1159 growth 1154:1159 growth of yeast harboring the sec53-V238M allele 1154:1208 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 7 40 theme yeast 1164:1168 arg1 glycosylation 1136:1148 protein glycosylation 1128:1148 protein glycosylation 1128:1148 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 9 41 theme Pgm1 1341:1344 arg1 activity 1346:1353 Pgm1 activity 1341:1353 Pgm1 activity 1341:1353 We find that reduction, but not elimination, of Pgm1 activity best compensates for the deleterious phenotypes associated with the sec53-V238M allele. 36214454 1 42 theme gene 202:205 arg1 215:218 215:218 215:218 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 1 42 theme gene 202:205 arg1 PMM2 207:213 the phosphomannomutase gene PMM2 179:213 the phosphomannomutase gene PMM2 179:213 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 0 43 theme deficiency 42:51 arg1 rescue 13:18 Evolutionary rescue 0:18 Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease 0:84 Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease. 36214454 6 44 theme minor 941:945 arg1 PGM1 910:920 PGM1 910:920 PGM1 910:920 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 6 44 theme minor 941:945 arg1 isoform 947:953 the minor isoform 937:953 the minor isoform of phosphoglucomutase in yeast 937:984 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 0 45 theme phosphomannomutase 23:40 arg1 deficiency 42:51 phosphomannomutase deficiency 23:51 phosphomannomutase deficiency 23:51 Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease. 36214454 4 46 theme most 538:541 arg1 populations 543:553 most populations 538:553 most populations 538:553 We find that after 1000 generations, most populations compensate for the slow-growth phenotype associated with the sec53 human-disease-associated alleles. 36214454 6 47 from yeast 980:984 arg1 PGM1 910:920 PGM1 910:920 PGM1 910:920 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 6 47 from yeast 980:984 arg1 isoform 947:953 the minor isoform 937:953 the minor isoform of phosphoglucomutase in yeast 937:984 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 5 48 theme genetic 760:766 arg1 interactors 768:778 known SEC53 genetic interactors 741:778 known SEC53 genetic interactors 741:778 Through whole-genome sequencing we identify compensatory mutations, including known SEC53 genetic interactors. 36214454 6 49 theme human 853:857 arg1 homologs 859:866 human homologs 853:866 human homologs 853:866 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 0 50 theme yeast 56:60 arg1 models 62:67 yeast models 56:67 yeast models of human disease 56:84 Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease. 36214454 5 51 theme known 741:745 arg1 interactors 768:778 known SEC53 genetic interactors 741:778 known SEC53 genetic interactors 741:778 Through whole-genome sequencing we identify compensatory mutations, including known SEC53 genetic interactors. 36214454 1 52 theme human 112:116 arg1 disorders 129:137 human congenital disorders 112:137 human congenital disorders of glycosylation (CDG) 112:160 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 8 53 theme enzymatic 1240:1248 arg1 activity 1250:1257 the enzymatic activity 1236:1257 the enzymatic activity of purified Pgm1 mutant proteins 1236:1290 Finally, we characterize the enzymatic activity of purified Pgm1 mutant proteins. 36214454 7 54 theme dominant 1061:1068 arg1 mutations 1047:1055 evolved pgm1 mutations 1027:1055 evolved pgm1 mutations 1027:1055 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 7 54 theme dominant 1061:1068 arg1 interactors 1098:1108 dominant and allele-specific genetic interactors 1061:1108 dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele 1061:1208 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 1 55 theme congenital 118:127 arg1 disorders 129:137 human congenital disorders 112:137 human congenital disorders of glycosylation (CDG) 112:160 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 1 56 from mutations 166:174 arg1 215:218 215:218 215:218 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 1 56 from mutations 166:174 arg1 PMM2 207:213 the phosphomannomutase gene PMM2 179:213 the phosphomannomutase gene PMM2 179:213 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 1 57 theme disorders 129:137 arg1 mutations 166:174 mutations 166:174 mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation 166:269 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 1 57 theme disorders 129:137 arg1 cause 103:107 The most common cause 87:107 The most common cause of human congenital disorders of glycosylation (CDG) 87:160 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 2 58 theme PMM2 327:337 arg1 gene 282:285 The yeast gene SEC53 272:298 The yeast gene SEC53 272:298 The yeast gene SEC53 encodes a homolog of human PMM2. 36214454 2 58 theme PMM2 327:337 arg1 homolog 310:316 a homolog 308:316 a homolog of human PMM2 308:337 The yeast gene SEC53 encodes a homolog of human PMM2. 36214454 0 59 theme human 72:76 arg1 disease 78:84 human disease 72:84 human disease 72:84 Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease. 36214454 7 60 gly glycosylation 1136:1148 arg1 yeast 1164:1168 yeast 1164:1168 yeast 1164:1168 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 6 61 from mutations 822:830 arg1 PGM1 910:920 PGM1 910:920 PGM1 910:920 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 6 61 from mutations 822:830 arg1 genes 841:845 other genes 835:845 other genes 835:845 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 7 62 theme genetic 990:996 arg1 reconstruction 998:1011 genetic reconstruction 990:1011 genetic reconstruction 990:1011 By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. 36214454 4 63 theme human-disease-associated 629:652 arg1 alleles 654:660 the sec53 human-disease-associated alleles 612:660 the sec53 human-disease-associated alleles 612:660 We find that after 1000 generations, most populations compensate for the slow-growth phenotype associated with the sec53 human-disease-associated alleles. 36214454 6 64 theme mutations 822:830 arg1 enrichment 795:804 an enrichment 792:804 an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast 792:984 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 36214454 1 65 theme glycosylation 142:154 arg1 disorders 129:137 human congenital disorders 112:137 human congenital disorders of glycosylation (CDG) 112:160 The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. 36214454 6 66 from phosphoglucomutase 958:975 arg1 yeast 980:984 yeast 980:984 yeast 980:984 We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. 35832442 13 0 theme lines 1799:1803 arg1 cycle 1780:1784 the cell cycle 1771:1784 the cell cycle of LUAD cell lines 1771:1803 The knockout or inhibition of STT3A suppressed proliferation, migration, and invasion, and arrested the cell cycle of LUAD cell lines in vitro. 35832442 9 1 theme xenograft 1182:1190 arg1 model 1192:1196 A mice xenograft model 1175:1196 A mice xenograft model 1175:1196 A mice xenograft model was established to investigate the effects of STT3A on tumor growth in vivo. 35832442 2 2 theme multiple 289:296 arg1 cancers 298:304 multiple cancers 289:304 multiple cancers 289:304 The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). 35832442 2 2 theme multiple 289:296 arg1 adenocarcinoma 322:335 lung adenocarcinoma 317:335 lung adenocarcinoma (LUAD) 317:342 The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). 35832442 16 3 theme PI3K/AKT 2211:2218 arg1 pathways 2230:2237 the MAPK and PI3K/AKT signaling pathways 2198:2237 pathways 2230:2237 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 11 4 theme normal 1561:1566 arg1 tissues 1573:1579 normal lung tissues 1561:1579 normal lung tissues 1561:1579 Results The expression of STT3A was frequently upregulated in LUAD tissues than normal lung tissues. 35832442 3 5 link N-linked 434:441 arg1 glycosyltransferase 443:461 N-linked glycosyltransferase 434:461 N-linked glycosyltransferase 434:461 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 8 6 theme Cell 1012:1015 arg1 assay 1050:1054 colony formation assay 1033:1054 colony formation assay 1033:1054 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 8 6 theme Cell 1012:1015 arg1 Counting 1017:1024 Cell Counting Kit-8 1012:1030 Cell Counting Kit-8 1012:1030 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 8 6 theme Cell 1012:1015 arg1 cytometry 1098:1106 flow cytometry 1093:1106 flow cytometry 1093:1106 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 8 6 theme Cell 1012:1015 arg1 wound-healing 1057:1069 wound-healing 1057:1069 wound-healing 1057:1069 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 8 6 theme Cell 1012:1015 arg1 assay 1082:1086 transwell assay 1072:1086 transwell assay 1072:1086 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 5 7 theme data 651:654 arg1 sets 656:659 public data sets 644:659 public data sets 644:659 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 2 8 theme lung 317:320 arg1 LUAD 338:341 LUAD 338:341 LUAD 338:341 The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). 35832442 2 8 theme lung 317:320 arg1 adenocarcinoma 322:335 lung adenocarcinoma 317:335 lung adenocarcinoma (LUAD) 317:342 The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). 35832442 14 9 theme tumor 1873:1877 arg1 growth 1879:1884 tumor growth 1873:1884 tumor growth 1873:1884 Similarly, the knockout or inhibition of STT3A suppressed tumor growth in vivo. 35832442 5 10 theme reaction 723:730 arg1 assays 771:776 quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays 683:776 quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples 683:801 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 1 11 theme proteins 204:211 arg1 stability 166:174 stability 166:174 stability 166:174 Background Glycosylation is crucial for the stability and biological functions of proteins. 35832442 1 11 theme proteins 204:211 arg1 functions 191:199 biological functions 180:199 biological functions 180:199 Background Glycosylation is crucial for the stability and biological functions of proteins. 35832442 12 12 theme STT3A 1605:1609 arg1 expression 1591:1600 The high expression 1582:1600 The high expression of STT3A 1582:1609 The high expression of STT3A was significantly associated with poor OS in LUAD patients. 35832442 5 13 theme Western 733:739 arg1 blot 741:744 Western blot 733:744 Western blot 733:744 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 2 14 gly glycosylation 227:239 arg1 proteins 253:260 critical proteins 244:260 critical proteins 244:260 The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). 35832442 5 15 theme quantitative 683:694 arg1 reaction 723:730 quantitative real-time polymerase chain reaction 683:730 quantitative real-time polymerase chain reaction 683:730 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 2 16 theme aberrant 218:225 arg1 glycosylation 227:239 The aberrant glycosylation 214:239 The aberrant glycosylation of critical proteins 214:260 The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). 35832442 14 17 theme knockout 1830:1837 arg1 inhibition 1842:1851 the knockout or inhibition 1826:1851 the knockout or inhibition of STT3A 1826:1860 Similarly, the knockout or inhibition of STT3A suppressed tumor growth in vivo. 35832442 9 18 theme mice 1177:1180 arg1 model 1192:1196 A mice xenograft model 1175:1196 A mice xenograft model 1175:1196 A mice xenograft model was established to investigate the effects of STT3A on tumor growth in vivo. 35832442 5 19 theme polymerase 706:715 arg1 reaction 723:730 quantitative real-time polymerase chain reaction 683:730 quantitative real-time polymerase chain reaction 683:730 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 16 20 theme potential 2291:2299 arg1 target 2313:2318 potential therapeutic target 2291:2318 potential therapeutic target 2291:2318 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 5 21 theme clinical 781:788 arg1 samples 795:801 clinical LUAD samples 781:801 clinical LUAD samples 781:801 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 15 22 theme molecular 1907:1915 arg1 mechanism 1917:1925 molecular mechanism 1907:1925 molecular mechanism 1907:1925 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 2 23 theme proteins 253:260 arg1 glycosylation 227:239 The aberrant glycosylation 214:239 The aberrant glycosylation of critical proteins 214:260 The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). 35832442 8 24 theme colony 1033:1038 arg1 assay 1050:1054 colony formation assay 1033:1054 colony formation assay 1033:1054 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 8 24 theme colony 1033:1038 arg1 Counting 1017:1024 Cell Counting Kit-8 1012:1030 Cell Counting Kit-8 1012:1030 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 3 25 theme complex 376:382 arg1 isoform 423:429 a major isoform 415:429 a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins 415:514 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 25 theme complex 376:382 arg1 STT3A 405:409 STT3A 405:409 STT3A 405:409 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 25 theme complex 376:382 arg1 A 402:402 STT3 oligosaccharyltransferase complex catalytic subunit A 345:402 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) 345:410 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 10 26 theme target 1420:1425 arg1 pathways 1427:1434 the target pathways 1416:1434 the target pathways 1416:1434 Further, the downstream signaling pathways of STT3A were screened by mass spectrometry with a bioinformatics analysis, and the activation of the target pathways were subsequently validated by Western blot. 35832442 10 27 theme bioinformatics 1369:1382 arg1 analysis 1384:1391 a bioinformatics analysis 1367:1391 a bioinformatics analysis 1367:1391 Further, the downstream signaling pathways of STT3A were screened by mass spectrometry with a bioinformatics analysis, and the activation of the target pathways were subsequently validated by Western blot. 35832442 16 28 theme LUAD 2324:2327 arg1 patients 2329:2336 LUAD patients 2324:2336 LUAD patients 2324:2336 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 16 29 theme prognostic 2266:2275 arg1 biomarker 2277:2285 a novel prognostic biomarker 2258:2285 a novel prognostic biomarker 2258:2285 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 16 29 theme prognostic 2266:2275 arg1 STT3A 2162:2166 Conclusions STT3A 2150:2166 Conclusions STT3A 2150:2166 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 3 30 theme STT3 345:348 arg1 isoform 423:429 a major isoform 415:429 a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins 415:514 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 30 theme STT3 345:348 arg1 STT3A 405:409 STT3A 405:409 STT3A 405:409 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 30 theme STT3 345:348 arg1 A 402:402 STT3 oligosaccharyltransferase complex catalytic subunit A 345:402 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) 345:410 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 10 31 theme Western 1467:1473 arg1 blot 1475:1478 Western blot 1467:1478 Western blot 1467:1478 Further, the downstream signaling pathways of STT3A were screened by mass spectrometry with a bioinformatics analysis, and the activation of the target pathways were subsequently validated by Western blot. 35832442 3 32 theme N-linked 434:441 arg1 glycosyltransferase 443:461 N-linked glycosyltransferase 434:461 N-linked glycosyltransferase 434:461 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 0 33 theme PI3K/AKT 94:101 arg1 pathway 113:119 the MAPK and PI3K/AKT signaling pathway 81:119 pathway 113:119 Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway. 35832442 16 34 theme signaling 2220:2228 arg1 pathways 2230:2237 the MAPK and PI3K/AKT signaling pathways 2198:2237 pathways 2230:2237 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 0 35 theme Targeting 0:8 arg1 STT3A 10:14 Targeting STT3A 0:14 Targeting STT3A 0:14 Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway. 35832442 8 36 theme transwell 1072:1080 arg1 Counting 1017:1024 Cell Counting Kit-8 1012:1030 Cell Counting Kit-8 1012:1030 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 8 36 theme transwell 1072:1080 arg1 assay 1082:1086 transwell assay 1072:1086 transwell assay 1072:1086 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 5 37 theme expression 588:597 arg1 profiles 599:606 The expression profiles 584:606 The expression profiles of STT3A 584:615 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 3 38 theme subunit 394:400 arg1 isoform 423:429 a major isoform 415:429 a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins 415:514 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 38 theme subunit 394:400 arg1 STT3A 405:409 STT3A 405:409 STT3A 405:409 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 38 theme subunit 394:400 arg1 A 402:402 STT3 oligosaccharyltransferase complex catalytic subunit A 345:402 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) 345:410 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 10 39 theme signaling 1299:1307 arg1 pathways 1309:1316 the downstream signaling pathways 1284:1316 the downstream signaling pathways of STT3A 1284:1325 Further, the downstream signaling pathways of STT3A were screened by mass spectrometry with a bioinformatics analysis, and the activation of the target pathways were subsequently validated by Western blot. 35832442 12 40 theme poor 1645:1648 arg1 OS 1650:1651 poor OS 1645:1651 poor OS in LUAD patients 1645:1668 The high expression of STT3A was significantly associated with poor OS in LUAD patients. 35832442 6 41 with patients 838:845 arg1 expression 871:880 high and low STT3A expression 852:880 high and low STT3A expression 852:880 The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. 35832442 3 42 gly glycosylation 482:494 arg1 proteins 507:514 various proteins 499:514 various proteins 499:514 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 16 43 theme novel 2260:2264 arg1 biomarker 2277:2285 a novel prognostic biomarker 2258:2285 a novel prognostic biomarker 2258:2285 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 16 43 theme novel 2260:2264 arg1 STT3A 2162:2166 Conclusions STT3A 2150:2166 Conclusions STT3A 2150:2166 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 0 44 theme anti-tumor 28:37 arg1 effect 39:44 an anti-tumor effect 25:44 an anti-tumor effect in lung adenocarcinoma 25:67 Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway. 35832442 8 45 theme flow 1093:1096 arg1 Counting 1017:1024 Cell Counting Kit-8 1012:1030 Cell Counting Kit-8 1012:1030 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 8 45 theme flow 1093:1096 arg1 cytometry 1098:1106 flow cytometry 1093:1106 flow cytometry 1093:1106 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 6 46 theme STT3A 865:869 arg1 expression 871:880 high and low STT3A expression 852:880 high and low STT3A expression 852:880 The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. 35832442 15 47 theme LUAD 1946:1949 arg1 progression 1951:1961 LUAD progression 1946:1961 LUAD progression 1946:1961 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 1 48 dep stability 166:174 arg1 the 162:164 the 162:164 the 162:164 Background Glycosylation is crucial for the stability and biological functions of proteins. 35832442 3 49 theme proteins 507:514 arg1 glycosylation 482:494 the glycosylation 478:494 the glycosylation of various proteins 478:514 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 6 50 with curve 916:920 arg1 analysis 938:945 a log-rank analysis 927:945 a log-rank analysis 927:945 The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. 35832442 6 51 theme log-rank 929:936 arg1 analysis 938:945 a log-rank analysis 927:945 a log-rank analysis 927:945 The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. 35832442 15 52 dep kinase 2007:2012 arg1 pathways 2087:2094 B (PI3K/AKT) pathways 2074:2094 B (PI3K/AKT) pathways 2074:2094 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 13 53 theme cell 1794:1797 arg1 lines 1799:1803 LUAD cell lines 1789:1803 LUAD cell lines 1789:1803 The knockout or inhibition of STT3A suppressed proliferation, migration, and invasion, and arrested the cell cycle of LUAD cell lines in vitro. 35832442 4 54 from functions 530:538 arg1 LUAD 552:555 LUAD 552:555 LUAD 552:555 However, the functions of STT3A in LUAD are still unclear. 35832442 16 55 dep potential 2291:2299 arg1 therapeutic 2301:2311 therapeutic 2301:2311 therapeutic 2301:2311 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 5 56 dep Methods 576:582 arg1 analyzed 632:639 analyzed 632:639 initially analyzed in public data sets 622:659 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 5 56 dep Methods 576:582 arg1 validated 670:678 validated 670:678 then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples 665:801 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 6 57 theme overall 808:814 arg1 OS 826:827 OS 826:827 OS 826:827 The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. 35832442 6 57 theme overall 808:814 arg1 survival 816:823 The overall survival 804:823 The overall survival (OS) between patients with high and low STT3A expression 804:880 The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. 35832442 11 58 theme LUAD 1543:1546 arg1 tissues 1548:1554 LUAD tissues 1543:1554 LUAD tissues 1543:1554 Results The expression of STT3A was frequently upregulated in LUAD tissues than normal lung tissues. 35832442 8 59 theme STT3A 1159:1163 arg1 functions 1146:1154 the cellular functions 1133:1154 the cellular functions of STT3A 1133:1163 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 6 60 theme Kaplan-Meier 903:914 arg1 curve 916:920 a Kaplan-Meier curve 901:920 a Kaplan-Meier curve with a log-rank analysis 901:945 The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. 35832442 13 61 theme cell 1775:1778 arg1 cycle 1780:1784 the cell cycle 1771:1784 the cell cycle of LUAD cell lines 1771:1803 The knockout or inhibition of STT3A suppressed proliferation, migration, and invasion, and arrested the cell cycle of LUAD cell lines in vitro. 35832442 9 62 from effects 1233:1239 arg1 growth 1259:1264 tumor growth 1253:1264 tumor growth in vivo 1253:1272 A mice xenograft model was established to investigate the effects of STT3A on tumor growth in vivo. 35832442 12 63 from OS 1650:1651 arg1 patients 1661:1668 LUAD patients 1656:1668 LUAD patients 1656:1668 The high expression of STT3A was significantly associated with poor OS in LUAD patients. 35832442 5 64 theme public 644:649 arg1 sets 656:659 public data sets 644:659 public data sets 644:659 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 11 65 theme lung 1568:1571 arg1 tissues 1573:1579 normal lung tissues 1561:1579 normal lung tissues 1561:1579 Results The expression of STT3A was frequently upregulated in LUAD tissues than normal lung tissues. 35832442 1 66 theme biological 180:189 arg1 functions 191:199 biological functions 180:199 biological functions 180:199 Background Glycosylation is crucial for the stability and biological functions of proteins. 35832442 16 67 theme LUAD 2177:2180 arg1 progression 2182:2192 LUAD progression 2177:2192 LUAD progression 2177:2192 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 5 68 theme chain 717:721 arg1 reaction 723:730 quantitative real-time polymerase chain reaction 683:730 quantitative real-time polymerase chain reaction 683:730 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 15 69 theme epithelial-mesenchymal 2115:2136 arg1 transition 2138:2147 the epithelial-mesenchymal transition 2111:2147 the epithelial-mesenchymal transition 2111:2147 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 16 70 theme Conclusions 2150:2160 arg1 biomarker 2277:2285 a novel prognostic biomarker 2258:2285 a novel prognostic biomarker 2258:2285 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 16 70 theme Conclusions 2150:2160 arg1 STT3A 2162:2166 Conclusions STT3A 2150:2166 Conclusions STT3A 2150:2166 Conclusions STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients. 35832442 5 71 from assays 771:776 arg1 samples 795:801 clinical LUAD samples 781:801 clinical LUAD samples 781:801 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 2 72 theme critical 244:251 arg1 proteins 253:260 critical proteins 244:260 critical proteins 244:260 The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). 35832442 9 73 theme STT3A 1244:1248 arg1 effects 1233:1239 the effects 1229:1239 the effects of STT3A on tumor growth in vivo 1229:1272 A mice xenograft model was established to investigate the effects of STT3A on tumor growth in vivo. 35832442 14 74 theme or 1839:1840 arg1 inhibition 1842:1851 the knockout or inhibition 1826:1851 the knockout or inhibition of STT3A 1826:1860 Similarly, the knockout or inhibition of STT3A suppressed tumor growth in vivo. 35832442 12 75 theme high 1586:1589 arg1 expression 1591:1600 The high expression 1582:1600 The high expression of STT3A 1582:1609 The high expression of STT3A was significantly associated with poor OS in LUAD patients. 35832442 13 76 theme STT3A 1701:1705 arg1 knockout 1675:1682 knockout 1675:1682 knockout 1675:1682 The knockout or inhibition of STT3A suppressed proliferation, migration, and invasion, and arrested the cell cycle of LUAD cell lines in vitro. 35832442 5 77 theme real-time 696:704 arg1 reaction 723:730 quantitative real-time polymerase chain reaction 683:730 quantitative real-time polymerase chain reaction 683:730 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 9 78 theme tumor 1253:1257 arg1 growth 1259:1264 tumor growth 1253:1264 tumor growth in vivo 1253:1272 A mice xenograft model was established to investigate the effects of STT3A on tumor growth in vivo. 35832442 2 79 theme important 271:279 arg1 role 281:284 an important role 268:284 an important role 268:284 The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). 35832442 1 80 theme Background 122:131 arg1 Glycosylation 133:145 Background Glycosylation 122:145 Background Glycosylation 122:145 Background Glycosylation is crucial for the stability and biological functions of proteins. 35832442 11 81 theme STT3A 1507:1511 arg1 expression 1493:1502 The expression 1489:1502 The expression of STT3A 1489:1511 Results The expression of STT3A was frequently upregulated in LUAD tissues than normal lung tissues. 35832442 5 82 theme LUAD 790:793 arg1 samples 795:801 clinical LUAD samples 781:801 clinical LUAD samples 781:801 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 8 83 theme formation 1040:1048 arg1 assay 1050:1054 colony formation assay 1033:1054 colony formation assay 1033:1054 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 8 83 theme formation 1040:1048 arg1 Counting 1017:1024 Cell Counting Kit-8 1012:1030 Cell Counting Kit-8 1012:1030 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 10 84 theme pathways 1427:1434 arg1 activation 1402:1411 the activation 1398:1411 the activation of the target pathways 1398:1434 Further, the downstream signaling pathways of STT3A were screened by mass spectrometry with a bioinformatics analysis, and the activation of the target pathways were subsequently validated by Western blot. 35832442 5 85 theme blot 741:744 arg1 assays 771:776 quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays 683:776 quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples 683:801 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 5 86 theme STT3A 611:615 arg1 profiles 599:606 The expression profiles 584:606 The expression profiles of STT3A 584:615 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 3 87 theme catalytic 384:392 arg1 isoform 423:429 a major isoform 415:429 a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins 415:514 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 87 theme catalytic 384:392 arg1 STT3A 405:409 STT3A 405:409 STT3A 405:409 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 87 theme catalytic 384:392 arg1 A 402:402 STT3 oligosaccharyltransferase complex catalytic subunit A 345:402 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) 345:410 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 15 88 theme mechanism 1917:1925 arg1 terms 1898:1902 terms 1898:1902 terms of molecular mechanism 1898:1925 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 11 89 dep Results 1481:1487 arg1 upregulated 1528:1538 upregulated 1528:1538 was frequently upregulated in LUAD tissues than normal lung tissues 1513:1579 Results The expression of STT3A was frequently upregulated in LUAD tissues than normal lung tissues. 35832442 0 90 theme signaling 103:111 arg1 pathway 113:119 the MAPK and PI3K/AKT signaling pathway 81:119 pathway 113:119 Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway. 35832442 14 91 theme STT3A 1856:1860 arg1 inhibition 1842:1851 the knockout or inhibition 1826:1851 the knockout or inhibition of STT3A 1826:1860 Similarly, the knockout or inhibition of STT3A suppressed tumor growth in vivo. 35832442 3 92 theme oligosaccharyltransferase 350:374 arg1 isoform 423:429 a major isoform 415:429 a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins 415:514 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 92 theme oligosaccharyltransferase 350:374 arg1 STT3A 405:409 STT3A 405:409 STT3A 405:409 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 92 theme oligosaccharyltransferase 350:374 arg1 A 402:402 STT3 oligosaccharyltransferase complex catalytic subunit A 345:402 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) 345:410 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 0 93 from effect 39:44 arg1 adenocarcinoma 54:67 lung adenocarcinoma 49:67 lung adenocarcinoma 49:67 Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway. 35832442 5 94 theme immunohistochemistry 750:769 arg1 assays 771:776 quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays 683:776 quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples 683:801 Methods The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. 35832442 12 95 theme LUAD 1656:1659 arg1 patients 1661:1668 LUAD patients 1656:1668 LUAD patients 1656:1668 The high expression of STT3A was significantly associated with poor OS in LUAD patients. 35832442 15 96 theme protein 1999:2005 arg1 MAPK 2015:2018 MAPK 2015:2018 MAPK 2015:2018 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 15 96 theme protein 1999:2005 arg1 kinase 2007:2012 the mitogen-activated protein kinase 1977:2012 the mitogen-activated protein kinase (MAPK) 1977:2019 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 15 97 theme mitogen-activated 1981:1997 arg1 MAPK 2015:2018 MAPK 2015:2018 MAPK 2015:2018 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 15 97 theme mitogen-activated 1981:1997 arg1 kinase 2007:2012 the mitogen-activated protein kinase 1977:2012 the mitogen-activated protein kinase (MAPK) 1977:2019 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 10 98 theme downstream 1288:1297 arg1 pathways 1309:1316 the downstream signaling pathways 1284:1316 the downstream signaling pathways of STT3A 1284:1325 Further, the downstream signaling pathways of STT3A were screened by mass spectrometry with a bioinformatics analysis, and the activation of the target pathways were subsequently validated by Western blot. 35832442 3 99 theme major 417:421 arg1 isoform 423:429 a major isoform 415:429 a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins 415:514 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 99 theme major 417:421 arg1 A 402:402 STT3 oligosaccharyltransferase complex catalytic subunit A 345:402 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) 345:410 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 4 100 theme STT3A 543:547 arg1 unclear 567:573 unclear 567:573 unclear 567:573 However, the functions of STT3A in LUAD are still unclear. 35832442 4 100 theme STT3A 543:547 arg1 functions 530:538 the functions 526:538 the functions of STT3A in LUAD 526:555 However, the functions of STT3A in LUAD are still unclear. 35832442 0 101 theme lung 49:52 arg1 adenocarcinoma 54:67 lung adenocarcinoma 49:67 lung adenocarcinoma 49:67 Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway. 35832442 6 102 theme low 861:863 arg1 expression 871:880 high and low STT3A expression 852:880 high and low STT3A expression 852:880 The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. 35832442 15 103 theme PI3K/AKT 2077:2084 arg1 pathways 2087:2094 B (PI3K/AKT) pathways 2074:2094 B (PI3K/AKT) pathways 2074:2094 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 10 104 theme STT3A 1321:1325 arg1 pathways 1309:1316 the downstream signaling pathways 1284:1316 the downstream signaling pathways of STT3A 1284:1325 Further, the downstream signaling pathways of STT3A were screened by mass spectrometry with a bioinformatics analysis, and the activation of the target pathways were subsequently validated by Western blot. 35832442 6 105 theme high 852:855 arg1 expression 871:880 high and low STT3A expression 852:880 high and low STT3A expression 852:880 The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. 35832442 15 106 theme B 2074:2074 arg1 pathways 2087:2094 B (PI3K/AKT) pathways 2074:2094 B (PI3K/AKT) pathways 2074:2094 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 3 107 theme various 499:505 arg1 proteins 507:514 various proteins 499:514 various proteins 499:514 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 8 108 theme cellular 1137:1144 arg1 functions 1146:1154 the cellular functions 1133:1154 the cellular functions of STT3A 1133:1163 Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. 35832442 15 109 theme protein 2059:2065 arg1 kinase 2067:2072 protein kinase 2059:2072 protein kinase 2059:2072 In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition. 35832442 3 110 theme glycosyltransferase 443:461 arg1 isoform 423:429 a major isoform 415:429 a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins 415:514 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 3 110 theme glycosyltransferase 443:461 arg1 A 402:402 STT3 oligosaccharyltransferase complex catalytic subunit A 345:402 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) 345:410 STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. 35832442 13 111 theme LUAD 1789:1792 arg1 lines 1799:1803 LUAD cell lines 1789:1803 LUAD cell lines 1789:1803 The knockout or inhibition of STT3A suppressed proliferation, migration, and invasion, and arrested the cell cycle of LUAD cell lines in vitro. 35832442 10 112 theme mass 1344:1347 arg1 spectrometry 1349:1360 mass spectrometry 1344:1360 mass spectrometry 1344:1360 Further, the downstream signaling pathways of STT3A were screened by mass spectrometry with a bioinformatics analysis, and the activation of the target pathways were subsequently validated by Western blot. 35372102 1 0 gly glycoproteins 146:158 arg1 glycoproteins 146:158 HIV-1 envelope (Env) glycoproteins 125:158 HIV-1 envelope (Env) glycoproteins 125:158 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 1 0 gly glycoproteins 146:158 arg1 Env 141:143 Env 141:143 Env 141:143 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 8 1 theme plasma 1364:1369 arg1 breadth 1353:1359 The neutralization breadth 1334:1359 The neutralization breadth of plasma from all four sequential samples 1334:1402 The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. 35372102 8 1 theme plasma 1364:1369 arg1 % 1411:1411 100% 1408:1411 100% 1408:1411 The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. 35372102 10 2 dep mutations 1578:1586 arg1 F277W 1588:1592 F277W 1588:1592 F277W 1588:1592 Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs. 35372102 6 3 theme autologous 1056:1065 arg1 plasma 1067:1072 concurrent and subsequent autologous plasma 1030:1072 concurrent and subsequent autologous plasma 1030:1072 While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. 35372102 8 4 theme neutralization 1338:1351 arg1 breadth 1353:1359 The neutralization breadth 1334:1359 The neutralization breadth of plasma from all four sequential samples 1334:1402 The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. 35372102 8 4 theme neutralization 1338:1351 arg1 % 1411:1411 100% 1408:1411 100% 1408:1411 The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. 35372102 10 5 theme viral 1693:1697 arg1 resistance 1699:1708 increased viral resistance 1683:1708 increased viral resistance to bNAbs 1683:1717 Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs. 35372102 8 6 theme sequential 1385:1394 arg1 samples 1396:1402 all four sequential samples 1376:1402 all four sequential samples 1376:1402 The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. 35372102 6 7 theme subsequent 1045:1054 arg1 plasma 1067:1072 concurrent and subsequent autologous plasma 1030:1072 concurrent and subsequent autologous plasma 1030:1072 While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. 35372102 2 8 theme non-progressor 535:548 arg1 patient 550:556 a long-term non-progressor patient 523:556 a long-term non-progressor patient with HIV-1 CRF07_BC infection 523:586 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 1 9 theme HIV-1 320:324 arg1 infection 326:334 HIV-1 infection 320:334 HIV-1 infection 320:334 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 8 10 theme HIV-1 1432:1436 arg1 panel 1448:1452 the global HIV-1 reference panel 1421:1452 the global HIV-1 reference panel 1421:1452 The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. 35372102 6 11 theme autologous 1224:1233 arg1 plasma 1235:1240 plasma 1235:1240 plasma 1235:1240 While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. 35372102 6 12 theme sampling 1174:1181 arg1 time 1183:1186 later sampling time 1168:1186 later sampling time 1168:1186 While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. 35372102 2 13 theme long-term 525:533 arg1 patient 550:556 a long-term non-progressor patient 523:556 a long-term non-progressor patient with HIV-1 CRF07_BC infection 523:586 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 1 14 theme infection 326:334 arg1 treatment 307:315 treatment 307:315 treatment 307:315 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 1 14 theme infection 326:334 arg1 prevention 292:301 prevention 292:301 prevention 292:301 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 4 15 from sites 819:823 arg1 V1 835:836 V1 835:836 V1 835:836 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 4 15 from sites 819:823 arg1 V5 842:843 V5 842:843 V5 842:843 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 4 16 theme glycosylation 805:817 arg1 sites 819:823 potential N-linked glycosylation sites 786:823 potential N-linked glycosylation sites (PNGS) in V1 and V5 786:843 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 4 16 theme glycosylation 805:817 arg1 PNGS 826:829 PNGS 826:829 PNGS 826:829 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 6 17 theme concurrent 1030:1039 arg1 plasma 1067:1072 concurrent and subsequent autologous plasma 1030:1072 concurrent and subsequent autologous plasma 1030:1072 While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. 35372102 1 18 dep prevention 292:301 arg1 the 288:290 the 288:290 the 288:290 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 0 19 with Patient 63:69 arg1 Focus 78:82 a Focus 76:82 a Focus on Evolution Over Time 76:105 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. 35372102 4 20 link patient-derived 746:760 arg1 genes 766:770 patient-derived Env genes 746:770 patient-derived Env genes 746:770 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 10 21 theme increased 1683:1691 arg1 resistance 1699:1708 increased viral resistance 1683:1708 increased viral resistance to bNAbs 1683:1717 Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs. 35372102 9 22 theme escape 1462:1467 arg1 mutants 1469:1475 Immune escape mutants 1455:1475 Immune escape mutants 1455:1475 Immune escape mutants resulted in increased resistance to bNAb targeting of different epitopes. 35372102 9 23 theme Immune 1455:1460 arg1 mutants 1469:1475 Immune escape mutants 1455:1475 Immune escape mutants 1455:1475 Immune escape mutants resulted in increased resistance to bNAb targeting of different epitopes. 35372102 1 24 theme glycoproteins 146:158 arg1 diversity 112:120 The diversity 108:120 The diversity of HIV-1 envelope (Env) glycoproteins 108:158 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 2 25 theme viral 441:445 arg1 evolution 447:455 viral evolution 441:455 viral evolution 441:455 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 8 26 theme reference 1438:1446 arg1 panel 1448:1452 the global HIV-1 reference panel 1421:1452 the global HIV-1 reference panel 1421:1452 The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. 35372102 7 27 theme Env-pseudotyped 1260:1274 arg1 viruses 1276:1282 All 24 Env-pseudotyped viruses 1253:1282 All 24 Env-pseudotyped viruses 1253:1282 All 24 Env-pseudotyped viruses were resistant to bNAbs 2G12, PGT121, and PGT135. 35372102 3 28 theme Fifty-nine 589:598 arg1 fragments 621:629 Fifty-nine full-length Env gene fragments 589:629 Fifty-nine full-length Env gene fragments 589:629 Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. 35372102 5 29 theme Env-pseudotyped 903:917 arg1 viruses 919:925 24 functional Env-pseudotyped viruses 889:925 24 functional Env-pseudotyped viruses 889:925 Further, 24 functional Env-pseudotyped viruses were generated based on Env gene sequences. 35372102 0 30 theme Neutralization 0:13 arg1 Sensitivity 15:25 Neutralization Sensitivity 0:25 Neutralization Sensitivity of HIV-1 0:34 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. 35372102 1 31 theme promising 238:246 arg1 antibodies 216:225 broadly neutralizing antibodies 195:225 broadly neutralizing antibodies (bNAbs) 195:233 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 1 31 theme promising 238:246 arg1 alternative 248:258 a promising alternative 236:258 a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection 236:334 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 3 32 theme full-length 600:610 arg1 fragments 621:629 Fifty-nine full-length Env gene fragments 589:629 Fifty-nine full-length Env gene fragments 589:629 Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. 35372102 2 33 theme immunogen 351:359 arg1 design 361:366 immunogen design 351:366 immunogen design 351:366 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 0 34 theme HIV-1 30:34 arg1 Sensitivity 15:25 Neutralization Sensitivity 0:25 Neutralization Sensitivity of HIV-1 0:34 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. 35372102 2 35 theme CRF07_BC 569:576 arg1 infection 578:586 HIV-1 CRF07_BC infection 563:586 HIV-1 CRF07_BC infection 563:586 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 8 36 theme global 1425:1430 arg1 panel 1448:1452 the global HIV-1 reference panel 1421:1452 the global HIV-1 reference panel 1421:1452 The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. 35372102 4 37 theme N-linked 796:803 arg1 sites 819:823 potential N-linked glycosylation sites 786:823 potential N-linked glycosylation sites (PNGS) in V1 and V5 786:843 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 4 37 theme N-linked 796:803 arg1 PNGS 826:829 PNGS 826:829 PNGS 826:829 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 2 38 theme antibodies 412:421 arg1 development 372:382 development 372:382 development 372:382 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 2 38 theme antibodies 412:421 arg1 design 361:366 immunogen design 351:366 immunogen design 351:366 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 10 39 theme mutation 1633:1640 arg1 S465T 1642:1646 previously uncharacterized mutation S465T 1606:1646 previously uncharacterized mutation S465T 1606:1646 Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs. 35372102 2 40 theme HIV-1 563:567 arg1 infection 578:586 HIV-1 CRF07_BC infection 563:586 HIV-1 CRF07_BC infection 563:586 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 0 41 from Focus 78:82 arg1 Evolution 87:95 Evolution 87:95 Evolution Over Time 87:105 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. 35372102 4 42 theme potential 786:794 arg1 sites 819:823 potential N-linked glycosylation sites 786:823 potential N-linked glycosylation sites (PNGS) in V1 and V5 786:843 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 4 42 theme potential 786:794 arg1 PNGS 826:829 PNGS 826:829 PNGS 826:829 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 2 43 theme neutralizing 399:410 arg1 antibodies 412:421 therapeutic neutralizing antibodies 387:421 therapeutic neutralizing antibodies 387:421 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 10 44 theme known 1572:1576 arg1 mutations 1578:1586 known mutations 1572:1586 known mutations F277W in gp41 1572:1600 Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs. 35372102 1 45 theme antiretroviral 263:276 arg1 drugs 278:282 antiretroviral drugs 263:282 antiretroviral drugs 263:282 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 2 46 theme therapeutic 387:397 arg1 antibodies 412:421 therapeutic neutralizing antibodies 387:421 therapeutic neutralizing antibodies 387:421 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 5 47 theme functional 892:901 arg1 viruses 919:925 24 functional Env-pseudotyped viruses 889:925 24 functional Env-pseudotyped viruses 889:925 Further, 24 functional Env-pseudotyped viruses were generated based on Env gene sequences. 35372102 2 48 theme patient 550:556 arg1 activity/sensitivity 499:518 activity/sensitivity 499:518 activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection 499:586 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 9 49 theme bNAb 1513:1516 arg1 targeting 1518:1526 bNAb targeting 1513:1526 bNAb targeting of different epitopes 1513:1548 Immune escape mutants resulted in increased resistance to bNAb targeting of different epitopes. 35372102 0 50 theme Untreated 53:61 arg1 Patient 63:69 an Untreated Patient 50:69 an Untreated Patient With a Focus on Evolution Over Time 50:105 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. 35372102 6 51 theme Env-pseudotyped 984:998 arg1 viruses 1000:1006 all 24 Env-pseudotyped viruses 977:1006 all 24 Env-pseudotyped viruses 977:1006 While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. 35372102 10 52 theme uncharacterized 1617:1631 arg1 S465T 1642:1646 previously uncharacterized mutation S465T 1606:1646 previously uncharacterized mutation S465T 1606:1646 Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs. 35372102 3 53 theme Env 612:614 arg1 fragments 621:629 Fifty-nine full-length Env gene fragments 589:629 Fifty-nine full-length Env gene fragments 589:629 Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. 35372102 6 54 theme Env-pseudotyped 1127:1141 arg1 viruses 1143:1149 Env-pseudotyped viruses 1127:1149 Env-pseudotyped viruses corresponding to later sampling time 1127:1186 While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. 35372102 4 55 theme patient-derived 746:760 arg1 genes 766:770 patient-derived Env genes 746:770 patient-derived Env genes 746:770 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 9 56 theme epitopes 1541:1548 arg1 targeting 1518:1526 bNAb targeting 1513:1526 bNAb targeting of different epitopes 1513:1548 Immune escape mutants resulted in increased resistance to bNAb targeting of different epitopes. 35372102 9 57 theme different 1531:1539 arg1 epitopes 1541:1548 different epitopes 1531:1548 different epitopes 1531:1548 Immune escape mutants resulted in increased resistance to bNAb targeting of different epitopes. 35372102 3 58 theme gene 616:619 arg1 fragments 621:629 Fifty-nine full-length Env gene fragments 589:629 Fifty-nine full-length Env gene fragments 589:629 Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. 35372102 5 59 theme gene 955:958 arg1 sequences 960:968 Env gene sequences 951:968 Env gene sequences 951:968 Further, 24 functional Env-pseudotyped viruses were generated based on Env gene sequences. 35372102 4 60 theme genes 766:770 arg1 Sequencing 732:741 Sequencing 732:741 Sequencing of patient-derived Env genes 732:770 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 2 61 with patient 550:556 arg1 infection 578:586 HIV-1 CRF07_BC infection 563:586 HIV-1 CRF07_BC infection 563:586 To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. 35372102 5 62 theme Env 951:953 arg1 sequences 960:968 Env gene sequences 951:968 Env gene sequences 951:968 Further, 24 functional Env-pseudotyped viruses were generated based on Env gene sequences. 35372102 3 63 theme plasma 654:659 arg1 samples 661:667 four plasma samples 649:667 four plasma samples sequentially harvested from the patient between 2016 and 2020 649:729 Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. 35372102 4 64 theme Env 762:764 arg1 genes 766:770 patient-derived Env genes 746:770 patient-derived Env genes 746:770 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 6 65 theme later 1168:1172 arg1 time 1183:1186 later sampling time 1168:1186 later sampling time 1168:1186 While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. 35372102 1 66 theme neutralizing 203:214 arg1 antibodies 216:225 broadly neutralizing antibodies 195:225 broadly neutralizing antibodies (bNAbs) 195:233 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 1 66 theme neutralizing 203:214 arg1 alternative 248:258 a promising alternative 236:258 a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection 236:334 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 1 66 theme neutralizing 203:214 arg1 bNAbs 228:232 bNAbs 228:232 bNAbs 228:232 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 4 67 gly glycosylation 805:817 arg2 PNGS 826:829 PNGS 826:829 PNGS 826:829 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 4 67 gly glycosylation 805:817 arg2 sites 819:823 potential N-linked glycosylation sites 786:823 potential N-linked glycosylation sites (PNGS) in V1 and V5 786:843 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 8 68 from samples 1396:1402 arg1 breadth 1353:1359 The neutralization breadth 1334:1359 The neutralization breadth of plasma from all four sequential samples 1334:1402 The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. 35372102 8 68 from samples 1396:1402 arg1 % 1411:1411 100% 1408:1411 100% 1408:1411 The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. 35372102 1 69 dep potency 172:178 arg1 the 168:170 the 168:170 the 168:170 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 9 70 theme increased 1489:1497 arg1 resistance 1499:1508 increased resistance 1489:1508 increased resistance to bNAb targeting of different epitopes 1489:1548 Immune escape mutants resulted in increased resistance to bNAb targeting of different epitopes. 35372102 1 71 theme HIV-1 125:129 arg1 glycoproteins 146:158 HIV-1 envelope (Env) glycoproteins 125:158 HIV-1 envelope (Env) glycoproteins 125:158 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 1 71 theme HIV-1 125:129 arg1 Env 141:143 Env 141:143 Env 141:143 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 3 72 attach derived 636:642 arg1 samples 661:667 four plasma samples 649:667 four plasma samples sequentially harvested from the patient between 2016 and 2020 649:729 Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. 35372102 3 72 attach derived 636:642 arg2 fragments 621:629 Fifty-nine full-length Env gene fragments 589:629 Fifty-nine full-length Env gene fragments 589:629 Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. 35372102 1 73 theme antibodies 216:225 arg1 breadth 184:190 breadth 184:190 breadth 184:190 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 1 73 theme antibodies 216:225 arg1 potency 172:178 potency 172:178 potency 172:178 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 4 74 link N-linked 796:803 arg1 sites 819:823 potential N-linked glycosylation sites 786:823 potential N-linked glycosylation sites (PNGS) in V1 and V5 786:843 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 4 74 link N-linked 796:803 arg1 PNGS 826:829 PNGS 826:829 PNGS 826:829 Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. 35372102 1 75 theme envelope 131:138 arg1 glycoproteins 146:158 HIV-1 envelope (Env) glycoproteins 125:158 HIV-1 envelope (Env) glycoproteins 125:158 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 35372102 1 75 theme envelope 131:138 arg1 Env 141:143 Env 141:143 Env 141:143 The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. 34731882 10 0 dep protein 1530:1536 arg1 S. 1538:1539 C4BP-bound protein S. 1519:1539 C4BP-bound protein S. 1519:1539 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 6 1 theme protein 734:740 arg1 LG1 744:746 protein S LG1 734:746 protein S LG1 734:746 To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. 34731882 11 2 dep S 1674:1674 arg1 Arg410 1700:1705 Arg410 1700:1705 Arg410 1700:1705 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 2 dep S 1674:1674 arg1 Glu257 1684:1689 Glu257 1684:1689 Glu257 1684:1689 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 2 dep S 1674:1674 arg1 Lys423 1708:1713 Lys423 1708:1713 Lys423 1708:1713 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 2 dep S 1674:1674 arg1 Glu424 1720:1725 Glu424 1720:1725 Glu424 1720:1725 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 2 dep S 1674:1674 arg1 Asp287 1692:1697 Asp287 1692:1697 Asp287 1692:1697 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 2 dep S 1674:1674 arg1 S 1674:1674 protein S 1666:1674 protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 1666:1725 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 4 3 theme cofactor 500:507 arg1 function 509:516 its TFPI cofactor function 491:516 its TFPI cofactor function 491:516 C4b binding protein (C4BP), which binds to protein S LG1, almost completely abolishes its TFPI cofactor function. 34731882 10 4 theme reduced 1485:1491 arg1 function 1507:1514 the reduced TFPI cofactor function 1481:1514 the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S 1481:1565 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 2 5 theme F 251:251 arg1 activity 256:263 factor (F)Xa activity 243:263 factor (F)Xa activity 243:263 It enhances TFPIα-mediated inhibition of factor (F)Xa activity and generation. 34731882 6 6 theme glycosylation 796:808 arg1 sites 821:825 inserted N-linked glycosylation attachment sites 778:825 inserted N-linked glycosylation attachment sites 778:825 To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. 34731882 2 7 theme factor 243:248 arg1 activity 256:263 factor (F)Xa activity 243:263 factor (F)Xa activity 243:263 It enhances TFPIα-mediated inhibition of factor (F)Xa activity and generation. 34731882 1 8 theme tissue 140:145 arg1 TFPI 173:176 TFPI 173:176 TFPI 173:176 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 1 8 theme tissue 140:145 arg1 inhibitor 162:170 tissue factor pathway inhibitor 140:170 the tissue factor pathway inhibitor (TFPI) anticoagulant pathway 136:199 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 8 9 theme charged 1082:1088 arg1 residues 1090:1097 4 to 6 surface-exposed charged residues 1059:1097 4 to 6 surface-exposed charged residues 1059:1097 Based on these results, we designed 4 protein S variants in which 4 to 6 surface-exposed charged residues were substituted for alanine. 34731882 6 10 theme inserted 778:785 arg1 sites 821:825 inserted N-linked glycosylation attachment sites 778:825 inserted N-linked glycosylation attachment sites 778:825 To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. 34731882 9 11 theme APC 1361:1363 arg1 function 1374:1381 normal APC cofactor function 1354:1381 normal APC cofactor function 1354:1381 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 10 12 theme cofactor 1498:1505 arg1 function 1507:1514 the reduced TFPI cofactor function 1481:1514 the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S 1481:1565 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 5 13 theme reduced 616:622 arg1 function 638:645 the reduced TFPI cofactor function 612:645 the reduced TFPI cofactor function of C4BP-bound protein S 612:669 However, neither the amino acids involved in TFPIα enhancement nor the mechanisms underlying the reduced TFPI cofactor function of C4BP-bound protein S are known. 34731882 2 14 theme Xa 253:254 arg1 activity 256:263 factor (F)Xa activity 243:263 factor (F)Xa activity 243:263 It enhances TFPIα-mediated inhibition of factor (F)Xa activity and generation. 34731882 10 15 theme protein 1557:1563 arg1 S 1565:1565 C4BP-bound protein S 1546:1565 C4BP-bound protein S 1546:1565 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 7 16 theme C4BP 979:982 arg1 binding 984:990 C4BP binding 979:990 C4BP binding 979:990 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 7 17 theme C 949:949 arg1 function 966:973 normal activated protein C (APC) cofactor function 924:973 normal activated protein C (APC) cofactor function 924:973 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 9 18 theme high-affinity 1387:1399 arg1 binding 1406:1412 high-affinity C4BP binding 1387:1412 high-affinity C4BP binding 1387:1412 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 10 19 theme protein 1530:1536 arg1 function 1507:1514 the reduced TFPI cofactor function 1481:1514 the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S 1481:1565 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 9 20 theme S 1150:1150 arg1 K255A/E257A/D287A/R410A/K423A/E424A 1152:1186 protein S K255A/E257A/D287A/R410A/K423A/E424A 1142:1186 protein S K255A/E257A/D287A/R410A/K423A/E424A 1142:1186 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 9 20 theme S 1150:1150 arg1 variant 1133:1139 One variant 1129:1139 One variant 1129:1139 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 7 21 theme activated 931:939 arg1 APC 952:954 APC 952:954 APC 952:954 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 7 21 theme activated 931:939 arg1 C 949:949 activated protein C 931:949 normal activated protein C (APC) cofactor function 924:973 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 11 22 theme protein 1666:1672 arg1 Arg410 1700:1705 Arg410 1700:1705 Arg410 1700:1705 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 22 theme protein 1666:1672 arg1 Glu257 1684:1689 Glu257 1684:1689 Glu257 1684:1689 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 22 theme protein 1666:1672 arg1 Lys423 1708:1713 Lys423 1708:1713 Lys423 1708:1713 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 22 theme protein 1666:1672 arg1 Glu424 1720:1725 Glu424 1720:1725 Glu424 1720:1725 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 22 theme protein 1666:1672 arg1 Asp287 1692:1697 Asp287 1692:1697 Asp287 1692:1697 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 22 theme protein 1666:1672 arg1 S 1674:1674 protein S 1666:1674 protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 1666:1725 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 11 23 theme β-chain 1813:1819 arg1 binding 1793:1799 binding 1793:1799 binding of the C4BP β-chain 1793:1819 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 0 24 theme TFPI 45:48 arg1 function 59:66 its TFPI cofactor function 41:66 its TFPI cofactor function 41:66 Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP. 34731882 8 25 dep 6 1064:1064 arg1 to 1061:1062 to 1061:1062 to 1061:1062 Based on these results, we designed 4 protein S variants in which 4 to 6 surface-exposed charged residues were substituted for alanine. 34731882 1 26 from cofactor 124:131 arg1 pathway 193:199 the tissue factor pathway inhibitor (TFPI) anticoagulant pathway 136:199 the tissue factor pathway inhibitor (TFPI) anticoagulant pathway 136:199 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 9 27 dep plasma 1262:1267 arg1 assays 1288:1293 inhibition assays 1277:1293 inhibition assays 1277:1293 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 9 27 dep plasma 1262:1267 arg1 both 1296:1299 both 1296:1299 both 1296:1299 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 4 28 theme C4b 405:407 arg1 protein 417:423 C4b binding protein 405:423 C4b binding protein (C4BP) 405:430 C4b binding protein (C4BP), which binds to protein S LG1, almost completely abolishes its TFPI cofactor function. 34731882 4 28 theme C4b 405:407 arg1 C4BP 426:429 C4BP 426:429 C4BP 426:429 C4b binding protein (C4BP), which binds to protein S LG1, almost completely abolishes its TFPI cofactor function. 34731882 3 29 theme G-type 390:395 arg1 LG 398:399 protein S laminin G-type (LG)-1 372:402 protein S laminin G-type (LG)-1 372:402 The enhancement is dependent on a TFPIα-protein S interaction involving TFPIα Kunitz 3 and protein S laminin G-type (LG)-1. 34731882 5 30 theme protein 661:667 arg1 S 669:669 C4BP-bound protein S 650:669 C4BP-bound protein S 650:669 However, neither the amino acids involved in TFPIα enhancement nor the mechanisms underlying the reduced TFPI cofactor function of C4BP-bound protein S are known. 34731882 9 31 theme cofactor 1241:1248 arg1 function 1250:1257 TFPI cofactor function 1236:1257 TFPI cofactor function 1236:1257 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 0 32 theme cofactor 50:57 arg1 function 59:66 its TFPI cofactor function 41:66 its TFPI cofactor function 41:66 Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP. 34731882 3 33 theme S 380:380 arg1 LG 398:399 protein S laminin G-type (LG)-1 372:402 protein S laminin G-type (LG)-1 372:402 The enhancement is dependent on a TFPIα-protein S interaction involving TFPIα Kunitz 3 and protein S laminin G-type (LG)-1. 34731882 0 34 theme Laminin 0:6 arg1 residues 11:18 Laminin G1 residues 0:18 Laminin G1 residues of protein S 0:31 Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP. 34731882 0 34 theme Laminin 0:6 arg1 S 31:31 protein S 23:31 protein S 23:31 Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP. 34731882 6 35 with variants 764:771 arg1 sites 821:825 inserted N-linked glycosylation attachment sites 778:825 inserted N-linked glycosylation attachment sites 778:825 To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. 34731882 3 36 theme S 329:329 arg1 interaction 331:341 a TFPIα-protein S interaction 313:341 a TFPIα-protein S interaction involving TFPIα Kunitz 3 and protein S laminin G-type (LG)-1 313:402 The enhancement is dependent on a TFPIα-protein S interaction involving TFPIα Kunitz 3 and protein S laminin G-type (LG)-1. 34731882 6 37 link N-linked 787:794 arg1 sites 821:825 inserted N-linked glycosylation attachment sites 778:825 inserted N-linked glycosylation attachment sites 778:825 To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. 34731882 7 38 theme normal 924:929 arg1 function 966:973 normal activated protein C (APC) cofactor function 924:973 normal activated protein C (APC) cofactor function 924:973 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 10 39 theme protein 1587:1593 arg1 S 1595:1595 C4BP β-chain-bound protein S 1568:1595 C4BP β-chain-bound protein S 1568:1595 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 0 40 theme protein 23:29 arg1 S 31:31 protein S 23:31 protein S 23:31 Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP. 34731882 9 41 theme inhibition 1277:1286 arg1 assays 1288:1293 inhibition assays 1277:1293 inhibition assays 1277:1293 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 10 42 theme cofactor 1623:1630 arg1 function 1632:1639 severely reduced TFPI cofactor function 1601:1639 severely reduced TFPI cofactor function 1601:1639 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 4 43 theme protein 448:454 arg1 LG1 458:460 protein S LG1 448:460 protein S LG1 448:460 C4b binding protein (C4BP), which binds to protein S LG1, almost completely abolishes its TFPI cofactor function. 34731882 10 44 theme reduced 1610:1616 arg1 function 1632:1639 severely reduced TFPI cofactor function 1601:1639 severely reduced TFPI cofactor function 1601:1639 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 7 45 theme S 836:836 arg1 D253T 838:842 Protein S D253T 828:842 Protein S D253T 828:842 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 1 46 theme anticoagulant 179:191 arg1 pathway 193:199 the tissue factor pathway inhibitor (TFPI) anticoagulant pathway 136:199 the tissue factor pathway inhibitor (TFPI) anticoagulant pathway 136:199 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 11 47 theme C4BP 1808:1811 arg1 β-chain 1813:1819 the C4BP β-chain 1804:1819 the C4BP β-chain 1804:1819 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 8 48 theme protein 1031:1037 arg1 variants 1041:1048 4 protein S variants 1029:1048 4 protein S variants in which 4 to 6 surface-exposed charged residues were substituted for alanine 1029:1126 Based on these results, we designed 4 protein S variants in which 4 to 6 surface-exposed charged residues were substituted for alanine. 34731882 11 49 theme S-mediated 1752:1761 arg1 enhancement 1763:1773 protein S-mediated enhancement 1744:1773 protein S-mediated enhancement of TFPIα 1744:1782 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 9 50 dep exhibited 1189:1197 arg1 abolished 1206:1214 abolished 1206:1214 abolished 1206:1214 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 9 50 dep exhibited 1189:1197 arg1 reduced 1228:1234 reduced 1228:1234 severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short 1219:1338 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 10 51 theme TFPI 1493:1496 arg1 function 1507:1514 the reduced TFPI cofactor function 1481:1514 the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S 1481:1565 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 5 52 theme TFPIα 564:568 arg1 enhancement 570:580 TFPIα enhancement 564:580 TFPIα enhancement 564:580 However, neither the amino acids involved in TFPIα enhancement nor the mechanisms underlying the reduced TFPI cofactor function of C4BP-bound protein S are known. 34731882 9 53 theme FV-short 1331:1338 arg1 presence 1308:1315 presence 1308:1315 presence 1308:1315 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 9 53 theme FV-short 1331:1338 arg1 absence 1320:1326 absence 1320:1326 absence 1320:1326 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 6 54 theme attachment 810:819 arg1 sites 821:825 inserted N-linked glycosylation attachment sites 778:825 inserted N-linked glycosylation attachment sites 778:825 To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. 34731882 4 55 theme TFPI 495:498 arg1 function 509:516 its TFPI cofactor function 491:516 its TFPI cofactor function 491:516 C4b binding protein (C4BP), which binds to protein S LG1, almost completely abolishes its TFPI cofactor function. 34731882 6 56 theme important 709:717 arg1 regions 719:725 functionally important regions 696:725 functionally important regions within protein S LG1 696:746 To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. 34731882 9 57 theme normal 1354:1359 arg1 function 1374:1381 normal APC cofactor function 1354:1381 normal APC cofactor function 1354:1381 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 6 58 theme N-linked 787:794 arg1 sites 821:825 inserted N-linked glycosylation attachment sites 778:825 inserted N-linked glycosylation attachment sites 778:825 To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. 34731882 10 59 theme C4BP-bound 1519:1528 arg1 protein 1530:1536 C4BP-bound protein S. 1519:1539 C4BP-bound protein S. 1519:1539 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 5 60 theme amino 540:544 arg1 acids 546:550 the amino acids 536:550 the amino acids involved in TFPIα enhancement 536:580 However, neither the amino acids involved in TFPIα enhancement nor the mechanisms underlying the reduced TFPI cofactor function of C4BP-bound protein S are known. 34731882 2 61 theme generation 269:278 arg1 inhibition 229:238 TFPIα-mediated inhibition 214:238 TFPIα-mediated inhibition of factor (F)Xa activity and generation 214:278 It enhances TFPIα-mediated inhibition of factor (F)Xa activity and generation. 34731882 1 62 theme factor 147:152 arg1 TFPI 173:176 TFPI 173:176 TFPI 173:176 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 1 62 theme factor 147:152 arg1 inhibitor 162:170 tissue factor pathway inhibitor 140:170 the tissue factor pathway inhibitor (TFPI) anticoagulant pathway 136:199 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 8 63 theme surface-exposed 1066:1080 arg1 residues 1090:1097 4 to 6 surface-exposed charged residues 1059:1097 4 to 6 surface-exposed charged residues 1059:1097 Based on these results, we designed 4 protein S variants in which 4 to 6 surface-exposed charged residues were substituted for alanine. 34731882 10 64 contain had 1597:1599 arg1 S 1595:1595 C4BP β-chain-bound protein S 1568:1595 C4BP β-chain-bound protein S 1568:1595 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 10 64 contain had 1597:1599 arg2 function 1632:1639 severely reduced TFPI cofactor function 1601:1639 severely reduced TFPI cofactor function 1601:1639 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 2 65 theme activity 256:263 arg1 inhibition 229:238 TFPIα-mediated inhibition 214:238 TFPIα-mediated inhibition of factor (F)Xa activity and generation 214:278 It enhances TFPIα-mediated inhibition of factor (F)Xa activity and generation. 34731882 7 66 theme TFPI 887:890 arg1 function 901:908 severely reduced TFPI cofactor function 870:908 severely reduced TFPI cofactor function 870:908 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 9 67 theme cofactor 1365:1372 arg1 function 1374:1381 normal APC cofactor function 1354:1381 normal APC cofactor function 1354:1381 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 9 68 dep presence 1308:1315 arg1 the 1304:1306 the 1304:1306 the 1304:1306 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 10 69 theme C4BP-bound 1546:1555 arg1 S 1565:1565 C4BP-bound protein S 1546:1565 C4BP-bound protein S 1546:1565 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 11 70 theme protein 1744:1750 arg1 enhancement 1763:1773 protein S-mediated enhancement 1744:1773 protein S-mediated enhancement of TFPIα 1744:1782 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 34731882 5 71 theme TFPI 624:627 arg1 function 638:645 the reduced TFPI cofactor function 612:645 the reduced TFPI cofactor function of C4BP-bound protein S 612:669 However, neither the amino acids involved in TFPIα enhancement nor the mechanisms underlying the reduced TFPI cofactor function of C4BP-bound protein S are known. 34731882 1 72 theme pathway 154:160 arg1 TFPI 173:176 TFPI 173:176 TFPI 173:176 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 1 72 theme pathway 154:160 arg1 inhibitor 162:170 tissue factor pathway inhibitor 140:170 the tissue factor pathway inhibitor (TFPI) anticoagulant pathway 136:199 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 7 73 theme cofactor 957:964 arg1 function 966:973 normal activated protein C (APC) cofactor function 924:973 normal activated protein C (APC) cofactor function 924:973 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 9 74 theme protein 1142:1148 arg1 K255A/E257A/D287A/R410A/K423A/E424A 1152:1186 protein S K255A/E257A/D287A/R410A/K423A/E424A 1142:1186 protein S K255A/E257A/D287A/R410A/K423A/E424A 1142:1186 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 9 74 theme protein 1142:1148 arg1 variant 1133:1139 One variant 1129:1139 One variant 1129:1139 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 9 75 theme C4BP 1401:1404 arg1 binding 1406:1412 high-affinity C4BP binding 1387:1412 high-affinity C4BP binding 1387:1412 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 6 76 gly glycosylation 796:808 arg2 sites 821:825 inserted N-linked glycosylation attachment sites 778:825 inserted N-linked glycosylation attachment sites 778:825 To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. 34731882 10 77 dep mechanisms 1463:1472 arg1 behind 1474:1479 behind 1474:1479 behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S 1474:1565 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 7 78 theme protein 941:947 arg1 APC 952:954 APC 952:954 APC 952:954 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 7 78 theme protein 941:947 arg1 C 949:949 activated protein C 931:949 normal activated protein C (APC) cofactor function 924:973 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 1 79 theme Protein 109:115 arg1 S 117:117 Protein S 109:117 Protein S 109:117 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 1 79 theme Protein 109:115 arg1 cofactor 124:131 a cofactor 122:131 a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway 122:199 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 5 80 theme S 669:669 arg1 function 638:645 the reduced TFPI cofactor function 612:645 the reduced TFPI cofactor function of C4BP-bound protein S 612:669 However, neither the amino acids involved in TFPIα enhancement nor the mechanisms underlying the reduced TFPI cofactor function of C4BP-bound protein S are known. 34731882 2 81 theme TFPIα-mediated 214:227 arg1 inhibition 229:238 TFPIα-mediated inhibition 214:238 TFPIα-mediated inhibition of factor (F)Xa activity and generation 214:278 It enhances TFPIα-mediated inhibition of factor (F)Xa activity and generation. 34731882 1 82 theme inhibitor 162:170 arg1 pathway 193:199 the tissue factor pathway inhibitor (TFPI) anticoagulant pathway 136:199 the tissue factor pathway inhibitor (TFPI) anticoagulant pathway 136:199 Protein S is a cofactor in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway. 34731882 10 83 theme C4BP 1568:1571 arg1 S 1595:1595 C4BP β-chain-bound protein S 1568:1595 C4BP β-chain-bound protein S 1568:1595 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 7 84 theme cofactor 892:899 arg1 function 901:908 severely reduced TFPI cofactor function 870:908 severely reduced TFPI cofactor function 870:908 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 3 85 theme TFPIα-protein 315:327 arg1 interaction 331:341 a TFPIα-protein S interaction 313:341 a TFPIα-protein S interaction involving TFPIα Kunitz 3 and protein S laminin G-type (LG)-1 313:402 The enhancement is dependent on a TFPIα-protein S interaction involving TFPIα Kunitz 3 and protein S laminin G-type (LG)-1. 34731882 4 86 theme binding 409:415 arg1 protein 417:423 C4b binding protein 405:423 C4b binding protein (C4BP) 405:430 C4b binding protein (C4BP), which binds to protein S LG1, almost completely abolishes its TFPI cofactor function. 34731882 4 86 theme binding 409:415 arg1 C4BP 426:429 C4BP 426:429 C4BP 426:429 C4b binding protein (C4BP), which binds to protein S LG1, almost completely abolishes its TFPI cofactor function. 34731882 5 87 theme C4BP-bound 650:659 arg1 S 669:669 C4BP-bound protein S 650:669 C4BP-bound protein S 650:669 However, neither the amino acids involved in TFPIα enhancement nor the mechanisms underlying the reduced TFPI cofactor function of C4BP-bound protein S are known. 34731882 9 88 theme TFPI 1236:1239 arg1 function 1250:1257 TFPI cofactor function 1236:1257 TFPI cofactor function 1236:1257 One variant, protein S K255A/E257A/D287A/R410A/K423A/E424A, exhibited either abolished or severely reduced TFPI cofactor function in plasma and FXa inhibition assays, both in the presence or absence of FV-short, but retained normal APC cofactor function and high-affinity C4BP binding. 34731882 7 89 theme reduced 879:885 arg1 function 901:908 severely reduced TFPI cofactor function 870:908 severely reduced TFPI cofactor function 870:908 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 0 90 theme G1 8:9 arg1 residues 11:18 Laminin G1 residues 0:18 Laminin G1 residues of protein S 0:31 Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP. 34731882 0 90 theme G1 8:9 arg1 S 31:31 protein S 23:31 protein S 23:31 Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP. 34731882 3 91 theme TFPIα 353:357 arg1 Kunitz 359:364 TFPIα Kunitz 3 353:366 TFPIα Kunitz 3 353:366 The enhancement is dependent on a TFPIα-protein S interaction involving TFPIα Kunitz 3 and protein S laminin G-type (LG)-1. 34731882 3 92 theme laminin 382:388 arg1 LG 398:399 protein S laminin G-type (LG)-1 372:402 protein S laminin G-type (LG)-1 372:402 The enhancement is dependent on a TFPIα-protein S interaction involving TFPIα Kunitz 3 and protein S laminin G-type (LG)-1. 34731882 0 93 theme S 31:31 arg1 residues 11:18 Laminin G1 residues 0:18 Laminin G1 residues of protein S 0:31 Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP. 34731882 0 93 theme S 31:31 arg1 S 31:31 protein S 23:31 protein S 23:31 Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP. 34731882 3 94 theme protein 372:378 arg1 LG 398:399 protein S laminin G-type (LG)-1 372:402 protein S laminin G-type (LG)-1 372:402 The enhancement is dependent on a TFPIα-protein S interaction involving TFPIα Kunitz 3 and protein S laminin G-type (LG)-1. 34731882 10 95 theme β-chain-bound 1573:1585 arg1 S 1595:1595 C4BP β-chain-bound protein S 1568:1595 C4BP β-chain-bound protein S 1568:1595 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 5 96 theme cofactor 629:636 arg1 function 638:645 the reduced TFPI cofactor function 612:645 the reduced TFPI cofactor function of C4BP-bound protein S 612:669 However, neither the amino acids involved in TFPIα enhancement nor the mechanisms underlying the reduced TFPI cofactor function of C4BP-bound protein S are known. 34731882 4 97 theme S 456:456 arg1 LG1 458:460 protein S LG1 448:460 protein S LG1 448:460 C4b binding protein (C4BP), which binds to protein S LG1, almost completely abolishes its TFPI cofactor function. 34731882 10 98 theme TFPI 1618:1621 arg1 function 1632:1639 severely reduced TFPI cofactor function 1601:1639 severely reduced TFPI cofactor function 1601:1639 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 7 99 theme Protein 828:834 arg1 D253T 838:842 Protein S D253T 828:842 Protein S D253T 828:842 Protein S D253T and Q427N/K429T displayed severely reduced TFPI cofactor function while showing normal activated protein C (APC) cofactor function and C4BP binding. 34731882 10 100 theme C4BP 1419:1422 arg1 β-chain 1424:1430 The C4BP β-chain 1415:1430 The C4BP β-chain 1415:1430 The C4BP β-chain was expressed to determine the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S. Like C4BP-bound protein S, C4BP β-chain-bound protein S had severely reduced TFPI cofactor function. 34731882 8 101 theme S 1039:1039 arg1 variants 1041:1048 4 protein S variants 1029:1048 4 protein S variants in which 4 to 6 surface-exposed charged residues were substituted for alanine 1029:1126 Based on these results, we designed 4 protein S variants in which 4 to 6 surface-exposed charged residues were substituted for alanine. 34731882 6 102 theme S 742:742 arg1 LG1 744:746 protein S LG1 734:746 protein S LG1 734:746 To screen for functionally important regions within protein S LG1, we generated 7 variants with inserted N-linked glycosylation attachment sites. 34731882 11 103 theme TFPIα 1778:1782 arg1 enhancement 1763:1773 protein S-mediated enhancement 1744:1773 protein S-mediated enhancement of TFPIα 1744:1782 These results show that protein S Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 are critical for protein S-mediated enhancement of TFPIα and that binding of the C4BP β-chain blocks this function. 35188715 6 0 theme prespecified 1036:1047 arg1 regimens 1059:1066 prespecified treatment regimens 1036:1066 prespecified treatment regimens 1036:1066 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 2 1 theme IgG 361:363 arg1 ACPA 365:368 IgG ACPA 361:368 IgG ACPA 361:368 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 12 2 theme RA 1827:1828 arg1 onset 1830:1834 RA onset 1827:1834 RA onset 1827:1834 While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. 35188715 12 3 from stable 1771:1776 arg1 disease 1793:1799 established disease 1781:1799 established disease 1781:1799 While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. 35188715 11 4 theme ACPA 1719:1722 arg1 response 1724:1731 the ACPA response 1715:1731 the ACPA response 1715:1731 CONCLUSION The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. 35188715 12 5 from onset 1830:1834 arg1 degree 1810:1815 a lower degree 1802:1815 a lower degree of VDG at RA onset 1802:1834 While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. 35188715 10 6 theme RA 1604:1605 arg1 onset 1607:1611 RA onset 1604:1611 RA onset 1604:1611 In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset. 35188715 1 7 theme OBJECTIVE 201:209 arg1 response 226:233 OBJECTIVE The autoimmune response 201:233 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) 201:262 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 6 8 with individuals 886:896 arg1 RA 1006:1007 new-onset/early RA 990:1007 new-onset/early RA 990:1007 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 6 8 with individuals 886:896 arg1 arthralgia 960:969 arthralgia 960:969 arthralgia 960:969 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 6 8 with individuals 886:896 arg1 RA 935:936 presymptomatic RA 920:936 presymptomatic RA 920:936 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 4 9 theme ACPA 646:649 arg1 VDG 651:653 IgG ACPA VDG 642:653 IgG ACPA VDG 642:653 To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. 35188715 1 10 theme autoimmune 215:224 arg1 response 226:233 OBJECTIVE The autoimmune response 201:233 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) 201:262 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 12 11 theme VDG 1820:1822 arg1 degree 1810:1815 a lower degree 1802:1815 a lower degree of VDG at RA onset 1802:1834 While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. 35188715 6 12 theme presymptomatic 920:933 arg1 RA 935:936 presymptomatic RA 920:936 presymptomatic RA 920:936 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 7 13 with patients 1119:1126 arg1 RA 1133:1134 RA 1133:1134 RA 1133:1134 Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up. 35188715 11 14 theme ACPA 1646:1649 arg1 VDG 1651:1653 IgG ACPA VDG 1642:1653 IgG ACPA VDG 1642:1653 CONCLUSION The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. 35188715 11 15 theme response 1724:1731 arg1 maturation 1701:1710 maturation 1701:1710 maturation of the ACPA response 1701:1731 CONCLUSION The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. 35188715 9 16 theme slight 1391:1396 arg1 increase 1398:1405 A slight increase 1389:1405 A slight increase in VDG 1389:1412 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 8 17 dep increased 1267:1275 arg1 P < 0.0001 1278:1287 P < 0.0001 1278:1287 P < 0.0001 1278:1287 RESULTS IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. 35188715 13 18 theme disease 2044:2050 arg1 development 2052:2062 disease development 2044:2062 disease development 2044:2062 Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development. 35188715 6 19 with patients 976:983 arg1 RA 1006:1007 new-onset/early RA 990:1007 new-onset/early RA 990:1007 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 6 19 with patients 976:983 arg1 arthralgia 960:969 arthralgia 960:969 arthralgia 960:969 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 6 19 with patients 976:983 arg1 RA 935:936 presymptomatic RA 920:936 presymptomatic RA 920:936 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 11 20 theme RA 1672:1673 arg1 onset 1675:1679 RA onset 1672:1679 RA onset 1672:1679 CONCLUSION The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. 35188715 1 21 from response 226:233 arg1 RA 260:261 RA 260:261 RA 260:261 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 1 21 from response 226:233 arg1 arthritis 249:257 rheumatoid arthritis 238:257 rheumatoid arthritis (RA) 238:262 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 6 22 theme healthy 878:884 arg1 individuals 886:896 106 healthy individuals 874:896 106 healthy individuals 874:896 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 4 23 theme different 692:700 arg1 stages 711:716 different clinical stages 692:716 different clinical stages 692:716 To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. 35188715 0 24 theme ~1,500 185:190 arg1 Samples 192:198 ~1,500 Samples 185:198 ~1,500 Samples 185:198 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 8 25 theme RESULTS 1232:1238 arg1 VDG 1249:1251 RESULTS IgG ACPA VDG 1232:1251 RESULTS IgG ACPA VDG 1232:1251 RESULTS IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. 35188715 2 26 theme variable 424:431 arg1 domain 433:438 the variable domain 420:438 the variable domain 420:438 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 8 27 theme ACPA 1244:1247 arg1 VDG 1249:1251 RESULTS IgG ACPA VDG 1232:1251 RESULTS IgG ACPA VDG 1232:1251 RESULTS IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. 35188715 7 28 theme long-term 1163:1171 arg1 DFR 1194:1196 DFR 1194:1196 DFR 1194:1196 Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up. 35188715 7 28 theme long-term 1163:1171 arg1 remission 1183:1191 long-term drug-free remission 1163:1191 long-term drug-free remission (DFR) 1163:1197 Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up. 35188715 9 29 with patients 1430:1437 arg1 RA 1456:1457 established RA 1444:1457 established RA 1444:1457 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 0 30 theme Rheumatoid 100:109 arg1 Arthritis 111:119 Rheumatoid Arthritis 100:119 Rheumatoid Arthritis 100:119 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 5 31 from Netherlands 837:847 arg1 profiles 781:788 IgG ACPA VDG profiles 768:788 IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 768:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 5 31 from Netherlands 837:847 arg1 cohorts 805:811 7 different cohorts 793:811 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 793:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 3 32 theme ACPA 466:469 arg1 glycosylation 487:499 ACPA variable domain glycosylation 466:499 ACPA variable domain glycosylation (VDG) across disease stages 466:527 However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. 35188715 3 32 theme ACPA 466:469 arg1 VDG 502:504 VDG 502:504 VDG 502:504 However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. 35188715 2 33 theme N-linked 400:407 arg1 glycans 409:415 N-linked glycans 400:415 N-linked glycans 400:415 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 13 34 theme biologic 1881:1888 arg1 mechanisms 1890:1899 the underlying biologic mechanisms 1866:1899 the underlying biologic mechanisms 1866:1899 Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development. 35188715 12 35 theme IgG 1740:1742 arg1 levels 1753:1758 IgG ACPA VDG levels 1740:1758 IgG ACPA VDG levels 1740:1758 While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. 35188715 9 36 theme moderate 1467:1474 arg1 influence 1476:1484 a moderate influence 1465:1484 a moderate influence of treatment (P = 0.007) 1465:1509 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 6 37 theme RA 1018:1019 arg1 patients 1021:1028 117 RA patients 1014:1028 117 RA patients 1014:1028 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 3 38 theme disease 514:520 arg1 stages 522:527 disease stages 514:527 disease stages 514:527 However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. 35188715 8 39 theme disease 1297:1303 arg1 onset 1305:1309 disease onset 1297:1309 disease onset 1297:1309 RESULTS IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. 35188715 0 40 theme IgG 0:2 arg1 Glycosylation 56:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 12 41 theme VDG 1749:1751 arg1 levels 1753:1758 IgG ACPA VDG levels 1740:1758 IgG ACPA VDG levels 1740:1758 While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. 35188715 0 42 dep Increases 70:78 arg1 Study 166:170 A Cross-Sectional Study 148:170 A Cross-Sectional Study Encompassing ~1,500 Samples 148:198 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 10 43 theme ACPA 1560:1563 arg1 VDG 1565:1567 IgG ACPA VDG 1556:1567 IgG ACPA VDG 1556:1567 In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset. 35188715 0 44 theme Protein 23:29 arg1 Glycosylation 56:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 1 45 theme protein 312:318 arg1 ACPAs 332:336 ACPAs 332:336 ACPAs 332:336 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 1 45 theme protein 312:318 arg1 antibodies 320:329 anti-citrullinated protein antibodies 293:329 anti-citrullinated protein antibodies (ACPAs) 293:337 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 0 46 theme Variable 40:47 arg1 Glycosylation 56:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 13 47 theme pre-disease 2007:2017 arg1 phase 2019:2023 the pre-disease phase 2003:2023 the pre-disease phase 2003:2023 Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development. 35188715 6 48 with patients 1021:1028 arg1 RA 1006:1007 new-onset/early RA 990:1007 new-onset/early RA 990:1007 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 6 48 with patients 1021:1028 arg1 arthralgia 960:969 arthralgia 960:969 arthralgia 960:969 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 6 48 with patients 1021:1028 arg1 RA 935:936 presymptomatic RA 920:936 presymptomatic RA 920:936 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 9 49 theme = 1502:1502 arg1 0.007 1504:1508 P = 0.007 1500:1508 P = 0.007 1500:1508 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 9 49 theme = 1502:1502 arg1 treatment 1489:1497 treatment 1489:1497 treatment (P = 0.007) 1489:1509 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 2 50 from expression 386:395 arg1 domain 433:438 the variable domain 420:438 the variable domain 420:438 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 5 51 theme liquid 733:738 arg1 chromatography 740:753 liquid chromatography 733:753 liquid chromatography 733:753 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 8 52 theme ACPA 1335:1338 arg1 levels 1340:1345 ACPA levels 1335:1345 ACPA levels 1335:1345 RESULTS IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. 35188715 3 53 theme glycosylation 487:499 arg1 presence 454:461 the presence 450:461 the presence of ACPA variable domain glycosylation (VDG) across disease stages 450:527 However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. 35188715 3 53 theme glycosylation 487:499 arg1 response 538:545 its response 534:545 its response to therapy 534:556 However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. 35188715 5 54 theme ACPA 772:775 arg1 profiles 781:788 IgG ACPA VDG profiles 768:788 IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 768:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 2 55 theme notable 342:348 arg1 feature 350:356 A notable feature 340:356 A notable feature of IgG ACPA 340:368 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 2 55 theme notable 342:348 arg1 expression 386:395 the abundant expression 373:395 the abundant expression of N-linked glycans in the variable domain 373:438 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 13 56 theme ACPA 1986:1989 arg1 response 1991:1998 the ACPA response 1982:1998 the ACPA response in the pre-disease phase 1982:2023 Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development. 35188715 12 57 from disease 1793:1799 arg1 stable 1771:1776 stable 1771:1776 stable 1771:1776 While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. 35188715 9 58 from increase 1398:1405 arg1 VDG 1410:1412 VDG 1410:1412 VDG 1410:1412 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 4 59 theme VDG 651:653 arg1 abundance 629:637 the abundance 625:637 the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages 625:716 To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. 35188715 6 60 theme treatment 1049:1057 arg1 regimens 1059:1066 prespecified treatment regimens 1036:1066 prespecified treatment regimens 1036:1066 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 2 61 theme ACPA 365:368 arg1 feature 350:356 A notable feature 340:356 A notable feature of IgG ACPA 340:368 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 2 61 theme ACPA 365:368 arg1 expression 386:395 the abundant expression 373:395 the abundant expression of N-linked glycans in the variable domain 373:438 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 6 62 with individuals 903:913 arg1 RA 1006:1007 new-onset/early RA 990:1007 new-onset/early RA 990:1007 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 6 62 with individuals 903:913 arg1 arthralgia 960:969 arthralgia 960:969 arthralgia 960:969 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 6 62 with individuals 903:913 arg1 RA 935:936 presymptomatic RA 920:936 presymptomatic RA 920:936 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 10 63 theme onset 1607:1611 arg1 time 1596:1599 the time 1592:1599 the time of RA onset 1592:1611 In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset. 35188715 4 64 from abundance 629:637 arg1 individuals 677:687 individuals 677:687 individuals in different clinical stages 677:716 To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. 35188715 4 64 from abundance 629:637 arg1 samples 664:670 1,498 samples 658:670 1,498 samples from individuals in different clinical stages 658:716 To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. 35188715 12 65 theme lower 1804:1808 arg1 degree 1810:1815 a lower degree 1802:1815 a lower degree of VDG at RA onset 1802:1834 While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. 35188715 4 66 theme IgG 642:644 arg1 VDG 651:653 IgG ACPA VDG 642:653 IgG ACPA VDG 642:653 To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. 35188715 5 67 theme different 795:803 arg1 cohorts 805:811 7 different cohorts 793:811 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 793:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 11 68 theme VDG 1651:1653 arg1 abundance 1629:1637 The abundance 1625:1637 The abundance of IgG ACPA VDG 1625:1653 CONCLUSION The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. 35188715 0 69 theme Cross-Sectional 150:164 arg1 Study 166:170 A Cross-Sectional Study 148:170 A Cross-Sectional Study Encompassing ~1,500 Samples 148:198 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 1 70 theme rheumatoid 238:247 arg1 RA 260:261 RA 260:261 RA 260:261 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 1 70 theme rheumatoid 238:247 arg1 arthritis 249:257 rheumatoid arthritis 238:257 rheumatoid arthritis (RA) 238:262 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 12 71 theme established 1781:1791 arg1 disease 1793:1799 established disease 1781:1799 established disease 1781:1799 While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. 35188715 9 72 located observed 1418:1425 arg2 increase 1398:1405 A slight increase 1389:1405 A slight increase in VDG 1389:1412 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 9 72 located observed 1418:1425 arg1 patients 1430:1437 patients 1430:1437 patients with established RA 1430:1457 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 11 73 dep CONCLUSION 1614:1623 arg1 increases 1655:1663 increases 1655:1663 increases toward RA onset 1655:1679 CONCLUSION The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. 35188715 11 73 dep CONCLUSION 1614:1623 arg1 correlates 1685:1694 correlates 1685:1694 correlates with maturation of the ACPA response 1685:1731 CONCLUSION The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. 35188715 5 74 from Japan 818:822 arg1 profiles 781:788 IgG ACPA VDG profiles 768:788 IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 768:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 5 74 from Japan 818:822 arg1 cohorts 805:811 7 different cohorts 793:811 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 793:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 3 75 theme variable 471:478 arg1 glycosylation 487:499 ACPA variable domain glycosylation 466:499 ACPA variable domain glycosylation (VDG) across disease stages 466:527 However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. 35188715 3 75 theme variable 471:478 arg1 VDG 502:504 VDG 502:504 VDG 502:504 However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. 35188715 6 76 with individuals 943:953 arg1 RA 1006:1007 new-onset/early RA 990:1007 new-onset/early RA 990:1007 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 6 76 with individuals 943:953 arg1 arthralgia 960:969 arthralgia 960:969 arthralgia 960:969 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 6 76 with individuals 943:953 arg1 RA 935:936 presymptomatic RA 920:936 presymptomatic RA 920:936 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 8 77 theme IgG 1240:1242 arg1 VDG 1249:1251 RESULTS IgG ACPA VDG 1232:1251 RESULTS IgG ACPA VDG 1232:1251 RESULTS IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. 35188715 9 78 theme established 1444:1454 arg1 RA 1456:1457 established RA 1444:1457 established RA 1444:1457 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 11 79 theme IgG 1642:1644 arg1 VDG 1651:1653 IgG ACPA VDG 1642:1653 IgG ACPA VDG 1642:1653 CONCLUSION The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. 35188715 0 80 theme Arthritis 111:119 arg1 Onset 91:95 the Onset 87:95 the Onset of Rheumatoid Arthritis 87:119 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 5 81 from Sweden 854:859 arg1 profiles 781:788 IgG ACPA VDG profiles 768:788 IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 768:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 5 81 from Sweden 854:859 arg1 cohorts 805:811 7 different cohorts 793:811 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 793:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 13 82 from phase 2019:2023 arg1 expansion 1969:1977 an expansion 1966:1977 an expansion of the ACPA response in the pre-disease phase 1966:2023 Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development. 35188715 13 83 theme underlying 1870:1879 arg1 mechanisms 1890:1899 the underlying biologic mechanisms 1866:1899 the underlying biologic mechanisms 1866:1899 Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development. 35188715 12 84 theme ACPA 1744:1747 arg1 levels 1753:1758 IgG ACPA VDG levels 1740:1758 IgG ACPA VDG levels 1740:1758 While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. 35188715 7 85 from patients 1119:1126 arg1 samples 1106:1112 234 samples 1102:1112 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up 1102:1229 Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up. 35188715 5 86 theme VDG 777:779 arg1 profiles 781:788 IgG ACPA VDG profiles 768:788 IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 768:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 5 87 from profiles 781:788 arg1 Sweden 854:859 Sweden 854:859 Sweden 854:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 5 87 from profiles 781:788 arg1 Netherlands 837:847 Netherlands 837:847 Netherlands 837:847 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 5 87 from profiles 781:788 arg1 Japan 818:822 Japan 818:822 Japan 818:822 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 5 87 from profiles 781:788 arg1 cohorts 805:811 7 different cohorts 793:811 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 793:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 5 87 from profiles 781:788 arg1 The 833:835 The 833:835 The 833:835 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 4 88 theme clinical 702:709 arg1 stages 711:716 different clinical stages 692:716 different clinical stages 692:716 To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. 35188715 2 89 theme abundant 377:384 arg1 feature 350:356 A notable feature 340:356 A notable feature of IgG ACPA 340:368 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 2 89 theme abundant 377:384 arg1 expression 386:395 the abundant expression 373:395 the abundant expression of N-linked glycans in the variable domain 373:438 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 0 90 theme Antibody 31:38 arg1 Glycosylation 56:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 1 91 theme anti-citrullinated 293:310 arg1 ACPAs 332:336 ACPAs 332:336 ACPAs 332:336 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 1 91 theme anti-citrullinated 293:310 arg1 antibodies 320:329 anti-citrullinated protein antibodies 293:329 anti-citrullinated protein antibodies (ACPAs) 293:337 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 9 92 theme treatment 1489:1497 arg1 influence 1476:1484 a moderate influence 1465:1484 a moderate influence of treatment (P = 0.007) 1465:1509 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 10 93 theme IgG 1556:1558 arg1 VDG 1565:1567 IgG ACPA VDG 1556:1567 IgG ACPA VDG 1556:1567 In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset. 35188715 0 94 theme Domain 49:54 arg1 Glycosylation 56:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 1 95 theme antibodies 320:329 arg1 presence 281:288 the presence 277:288 the presence of anti-citrullinated protein antibodies (ACPAs) 277:337 OBJECTIVE The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). 35188715 9 96 theme P 1500:1500 arg1 0.007 1504:1508 P = 0.007 1500:1508 P = 0.007 1500:1508 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 9 96 theme P 1500:1500 arg1 treatment 1489:1497 treatment 1489:1497 treatment (P = 0.007) 1489:1509 A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). 35188715 6 97 theme new-onset/early 990:1004 arg1 RA 1006:1007 new-onset/early RA 990:1007 new-onset/early RA 990:1007 We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. 35188715 13 98 from expansion 1969:1977 arg1 phase 2019:2023 the pre-disease phase 2003:2023 the pre-disease phase 2003:2023 Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development. 35188715 2 99 link N-linked 400:407 arg1 glycans 409:415 N-linked glycans 400:415 N-linked glycans 400:415 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 2 100 theme glycans 409:415 arg1 feature 350:356 A notable feature 340:356 A notable feature of IgG ACPA 340:368 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 2 100 theme glycans 409:415 arg1 expression 386:395 the abundant expression 373:395 the abundant expression of N-linked glycans in the variable domain 373:438 A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. 35188715 5 101 theme IgG 768:770 arg1 profiles 781:788 IgG ACPA VDG profiles 768:788 IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden 768:859 METHODS Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. 35188715 7 102 dep 16 years 1212:1219 arg1 to 1209:1210 to 1209:1210 to 1209:1210 Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up. 35188715 13 103 from response 1991:1998 arg1 phase 2019:2023 the pre-disease phase 2003:2023 the pre-disease phase 2003:2023 Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development. 35188715 3 104 theme domain 480:485 arg1 glycosylation 487:499 ACPA variable domain glycosylation 466:499 ACPA variable domain glycosylation (VDG) across disease stages 466:527 However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. 35188715 3 104 theme domain 480:485 arg1 VDG 502:504 VDG 502:504 VDG 502:504 However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. 35188715 4 105 from individuals 677:687 arg1 samples 664:670 1,498 samples 658:670 1,498 samples from individuals in different clinical stages 658:716 To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. 35188715 4 105 from individuals 677:687 arg1 stages 711:716 different clinical stages 692:716 different clinical stages 692:716 To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. 35188715 4 105 from individuals 677:687 arg1 abundance 629:637 the abundance 625:637 the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages 625:716 To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. 35188715 13 106 theme response 1991:1998 arg1 expansion 1969:1977 an expansion 1966:1977 an expansion of the ACPA response in the pre-disease phase 1966:2023 Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development. 35188715 8 107 theme epitope 1351:1357 arg1 spreading 1359:1367 epitope spreading 1351:1367 epitope spreading 1351:1367 RESULTS IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. 35188715 0 108 theme Anti-Citrullinated 4:21 arg1 Glycosylation 56:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation 0:68 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross-Sectional Study Encompassing ~1,500 Samples. 35188715 7 109 theme drug-free 1173:1181 arg1 DFR 1194:1196 DFR 1194:1196 DFR 1194:1196 Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up. 35188715 7 109 theme drug-free 1173:1181 arg1 remission 1183:1191 long-term drug-free remission 1163:1191 long-term drug-free remission (DFR) 1163:1197 Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up. 36480915 2 0 theme Pro 624:626 arg1 method 631:636 the timsTOF Pro MS method 612:636 the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment 612:712 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 2 0 theme Pro 624:626 arg1 effective 781:789 effective 781:789 effective 781:789 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 0 1 theme binding 193:199 arg1 properties 201:210 antigenic and receptor binding properties 170:210 properties 201:210 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 2 2 theme low-abundance 806:818 arg1 glycopeptides 820:832 low-abundance glycopeptides 806:832 low-abundance glycopeptides 806:832 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 0 3 theme precise 217:223 arg1 analyses 225:232 precise analyses 217:232 precise analyses of site-specific glycoforms in these proteins 217:278 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 1 4 theme glycoproteomic 403:416 arg1 approach 418:425 a glycoproteomic approach 401:425 a glycoproteomic approach 401:425 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 0 5 theme influenza 144:152 arg1 viruses 154:160 influenza viruses 144:160 influenza viruses 144:160 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 6 theme antigenic 314:322 arg1 properties 340:349 the antigenic and immunogenic properties 310:349 the antigenic and immunogenic properties of influenza viruses 310:370 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 3 7 gly glycopeptides 891:903 arg2 glycopeptides 891:903 intact site-specific glycopeptides 870:903 intact site-specific glycopeptides 870:903 We quantified the distributions of intact site-specific glycopeptides in hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) and A/mute swan/Rhode Island/A00325125/2008 (H7N3). 36480915 0 8 from proteins 271:278 arg1 analyses 225:232 precise analyses 217:232 precise analyses of site-specific glycoforms in these proteins 217:278 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 8 from proteins 271:278 arg1 Analyses 15:22 Glycoproteomic Analyses 0:22 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties 0:210 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 9 theme immunogenic 328:338 arg1 properties 340:349 the antigenic and immunogenic properties 310:349 the antigenic and immunogenic properties of influenza viruses 310:370 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 2 10 theme Exactive 596:603 arg1 MS 608:609 a Q Exactive HF MS 592:609 a Q Exactive HF MS 592:609 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 2 11 theme glycopeptide 731:742 arg1 coverage 744:751 similar glycopeptide coverage 723:751 similar glycopeptide coverage 723:751 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 5 12 theme Pro 1333:1335 arg1 data 1340:1343 the timsTOF Pro MS data 1321:1343 the timsTOF Pro MS data 1321:1343 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 3 13 theme intact 870:875 arg1 glycopeptides 891:903 intact site-specific glycopeptides 870:903 intact site-specific glycopeptides 870:903 We quantified the distributions of intact site-specific glycopeptides in hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) and A/mute swan/Rhode Island/A00325125/2008 (H7N3). 36480915 1 14 theme Pro 446:448 arg1 MS 469:470 MS 469:470 MS 469:470 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 1 14 theme Pro 446:448 arg1 spectrometer 455:466 a timsTOF Pro mass spectrometer 436:466 a timsTOF Pro mass spectrometer (MS) 436:471 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 3 15 theme A/chicken/Wuxi/0405005/2013 925:951 arg1 hemagglutinin 908:920 hemagglutinin 908:920 hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) 908:958 We quantified the distributions of intact site-specific glycopeptides in hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) and A/mute swan/Rhode Island/A00325125/2008 (H7N3). 36480915 0 16 theme viruses 364:370 arg1 properties 340:349 the antigenic and immunogenic properties 310:349 the antigenic and immunogenic properties of influenza viruses 310:370 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 17 theme N-Linked 69:76 arg1 glycosylation 78:90 N-Linked glycosylation 69:90 N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses 69:160 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 2 18 theme liquid 674:679 arg1 chromatography 681:694 the hydrophilic interaction liquid chromatography 646:694 the hydrophilic interaction liquid chromatography column enrichment 646:712 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 3 19 theme glycopeptides 891:903 arg1 distributions 853:865 the distributions 849:865 the distributions of intact site-specific glycopeptides in hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) and A/mute swan/Rhode Island/A00325125/2008 (H7N3) 849:1009 We quantified the distributions of intact site-specific glycopeptides in hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) and A/mute swan/Rhode Island/A00325125/2008 (H7N3). 36480915 6 20 theme timsTOF 1415:1421 arg1 MS 1427:1428 timsTOF Pro MS 1415:1428 timsTOF Pro MS method 1415:1435 In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production. 36480915 2 21 theme hydrophilic 650:660 arg1 chromatography 681:694 the hydrophilic interaction liquid chromatography 646:694 the hydrophilic interaction liquid chromatography column enrichment 646:712 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 5 22 theme glycopeptides 1388:1400 arg1 linkages 1372:1379 sialylation linkages 1360:1379 sialylation linkages of the glycopeptides 1360:1400 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 0 23 gly glycosylation 78:90 arg1 binding 193:199 antigenic and receptor binding properties 170:210 binding 193:199 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 23 gly glycosylation 78:90 arg1 viruses 154:160 influenza viruses 144:160 influenza viruses 144:160 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 23 gly glycosylation 78:90 arg1 glycoproteins 127:139 hemagglutinin and neuraminidase glycoproteins 95:139 hemagglutinin and neuraminidase glycoproteins 95:139 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 24 theme Glycoproteomic 0:13 arg1 Analyses 15:22 Glycoproteomic Analyses 0:22 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties 0:210 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 2 25 theme column 696:701 arg1 enrichment 703:712 the hydrophilic interaction liquid chromatography column enrichment 646:712 the hydrophilic interaction liquid chromatography column enrichment 646:712 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 5 26 theme sialylation 1360:1370 arg1 linkages 1372:1379 sialylation linkages 1360:1379 sialylation linkages of the glycopeptides 1360:1400 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 6 27 theme influenza 1483:1491 arg1 glycoproteins 1493:1505 influenza glycoproteins 1483:1505 influenza glycoproteins 1483:1505 In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production. 36480915 5 28 theme Collisional 1242:1252 arg1 CCS 1269:1271 CCS 1269:1271 CCS 1269:1271 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 5 28 theme Collisional 1242:1252 arg1 section 1260:1266 Collisional cross section 1242:1266 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data 1242:1343 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 6 29 gly glycoproteins 1493:1505 arg1 glycoproteins 1493:1505 influenza glycoproteins 1483:1505 influenza glycoproteins 1483:1505 In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production. 36480915 0 30 theme A 37:37 arg1 Viruses 39:45 Influenza A Viruses 27:45 Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties 27:210 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 3 31 from distributions 853:865 arg1 hemagglutinin 908:920 hemagglutinin 908:920 hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) 908:958 We quantified the distributions of intact site-specific glycopeptides in hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) and A/mute swan/Rhode Island/A00325125/2008 (H7N3). 36480915 3 31 from distributions 853:865 arg1 H7N3 1005:1008 H7N3 1005:1008 H7N3 1005:1008 We quantified the distributions of intact site-specific glycopeptides in hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) and A/mute swan/Rhode Island/A00325125/2008 (H7N3). 36480915 6 32 theme intact 1450:1455 arg1 glycans 1471:1477 intact site-specific glycans 1450:1477 intact site-specific glycans for influenza glycoproteins 1450:1505 In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production. 36480915 2 33 gly glycopeptide 731:742 arg2 glycopeptide 731:742 similar glycopeptide coverage 723:751 similar glycopeptide coverage 723:751 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 1 34 theme site-specific 521:533 arg1 glycosylation 535:547 site-specific glycosylation 521:547 site-specific glycosylation 521:547 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 0 35 gly glycoforms 251:260 arg2 proteins 271:278 these proteins 265:278 these proteins 265:278 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 6 36 theme vaccine 1556:1562 arg1 development 1564:1574 influenza vaccine development 1546:1574 influenza vaccine development 1546:1574 In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production. 36480915 6 37 theme site-specific 1457:1469 arg1 glycans 1471:1477 intact site-specific glycans 1450:1477 intact site-specific glycans for influenza glycoproteins 1450:1505 In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production. 36480915 4 38 theme high-mannose 1122:1133 arg1 glycans 1135:1141 N483 but only high-mannose glycans 1108:1141 N483 but only high-mannose glycans 1108:1141 Results showed that hemagglutinin for both viruses had complex N-glycans at N22, N38, N240, and N483 but only high-mannose glycans at N411 and, however, that the type and quantities of glycans were distinct between these viruses. 36480915 2 39 theme timsTOF 616:622 arg1 method 631:636 the timsTOF Pro MS method 612:636 the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment 612:712 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 2 39 theme timsTOF 616:622 arg1 effective 781:789 effective 781:789 effective 781:789 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 4 40 theme glycans 1197:1203 arg1 quantities 1183:1192 quantities 1183:1192 quantities 1183:1192 Results showed that hemagglutinin for both viruses had complex N-glycans at N22, N38, N240, and N483 but only high-mannose glycans at N411 and, however, that the type and quantities of glycans were distinct between these viruses. 36480915 4 40 theme glycans 1197:1203 arg1 type 1174:1177 type 1174:1177 type 1174:1177 Results showed that hemagglutinin for both viruses had complex N-glycans at N22, N38, N240, and N483 but only high-mannose glycans at N411 and, however, that the type and quantities of glycans were distinct between these viruses. 36480915 6 41 theme MS 1427:1428 arg1 method 1430:1435 timsTOF Pro MS method 1415:1435 timsTOF Pro MS method 1415:1435 In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production. 36480915 0 42 theme site-specific 237:249 arg1 glycoforms 251:260 site-specific glycoforms 237:260 site-specific glycoforms in these proteins 237:278 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 1 43 gly heterogeneity 504:516 arg1 glycosylation 535:547 site-specific glycosylation 521:547 site-specific glycosylation 521:547 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 2 44 theme MS 628:629 arg1 method 631:636 the timsTOF Pro MS method 612:636 the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment 612:712 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 2 44 theme MS 628:629 arg1 effective 781:789 effective 781:789 effective 781:789 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 5 45 from data 1340:1343 arg1 spectrometry 1303:1314 the ion mobility spectrometry 1286:1314 the ion mobility spectrometry from the timsTOF Pro MS data 1286:1343 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 4 46 dep had 1063:1065 arg1 distinct 1210:1217 distinct 1210:1217 distinct 1210:1217 Results showed that hemagglutinin for both viruses had complex N-glycans at N22, N38, N240, and N483 but only high-mannose glycans at N411 and, however, that the type and quantities of glycans were distinct between these viruses. 36480915 0 47 from glycosylation 78:90 arg1 glycoproteins 127:139 hemagglutinin and neuraminidase glycoproteins 95:139 hemagglutinin and neuraminidase glycoproteins 95:139 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 48 theme viruses 154:160 arg1 glycosylation 78:90 N-Linked glycosylation 69:90 N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses 69:160 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 6 49 theme Pro 1423:1425 arg1 MS 1427:1428 timsTOF Pro MS 1415:1428 timsTOF Pro MS method 1415:1435 In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production. 36480915 0 50 theme antigenic 170:178 arg1 properties 201:210 antigenic and receptor binding properties 170:210 properties 201:210 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 51 gly glycoproteins 127:139 arg1 glycoproteins 127:139 hemagglutinin and neuraminidase glycoproteins 95:139 hemagglutinin and neuraminidase glycoproteins 95:139 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 1 52 gly glycoproteins 563:575 arg1 glycoproteins 563:575 influenza glycoproteins 553:575 influenza glycoproteins 553:575 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 2 53 theme HF 605:606 arg1 MS 608:609 a Q Exactive HF MS 592:609 a Q Exactive HF MS 592:609 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 5 54 theme timsTOF 1325:1331 arg1 data 1340:1343 the timsTOF Pro MS data 1321:1343 the timsTOF Pro MS data 1321:1343 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 0 55 theme receptor 184:191 arg1 properties 201:210 antigenic and receptor binding properties 170:210 properties 201:210 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 1 56 theme timsTOF 438:444 arg1 MS 469:470 MS 469:470 MS 469:470 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 1 56 theme timsTOF 438:444 arg1 spectrometer 455:466 a timsTOF Pro mass spectrometer 436:466 a timsTOF Pro mass spectrometer (MS) 436:471 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 2 57 theme Q 594:594 arg1 MS 608:609 a Q Exactive HF MS 592:609 a Q Exactive HF MS 592:609 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 0 58 from glycoforms 251:260 arg1 proteins 271:278 these proteins 265:278 these proteins 265:278 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 5 59 theme MS 1337:1338 arg1 data 1340:1343 the timsTOF Pro MS data 1321:1343 the timsTOF Pro MS data 1321:1343 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 3 60 theme site-specific 877:889 arg1 glycopeptides 891:903 intact site-specific glycopeptides 870:903 intact site-specific glycopeptides 870:903 We quantified the distributions of intact site-specific glycopeptides in hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) and A/mute swan/Rhode Island/A00325125/2008 (H7N3). 36480915 1 61 theme mass 450:453 arg1 MS 469:470 MS 469:470 MS 469:470 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 1 61 theme mass 450:453 arg1 spectrometer 455:466 a timsTOF Pro mass spectrometer 436:466 a timsTOF Pro mass spectrometer (MS) 436:471 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 4 62 theme complex 1067:1073 arg1 N-glycans 1075:1083 complex N-glycans 1067:1083 complex N-glycans 1067:1083 Results showed that hemagglutinin for both viruses had complex N-glycans at N22, N38, N240, and N483 but only high-mannose glycans at N411 and, however, that the type and quantities of glycans were distinct between these viruses. 36480915 5 63 theme mobility 1294:1301 arg1 spectrometry 1303:1314 the ion mobility spectrometry 1286:1314 the ion mobility spectrometry from the timsTOF Pro MS data 1286:1343 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 0 64 theme influenza 354:362 arg1 viruses 364:370 influenza viruses 354:370 influenza viruses 354:370 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 1 65 dep abundance 490:498 arg1 the 486:488 the 486:488 the 486:488 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 0 66 from Analyses 15:22 arg1 proteins 271:278 these proteins 265:278 these proteins 265:278 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 2 67 theme chromatography 681:694 arg1 enrichment 703:712 the hydrophilic interaction liquid chromatography column enrichment 646:712 the hydrophilic interaction liquid chromatography column enrichment 646:712 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 0 68 theme hemagglutinin 95:107 arg1 glycoproteins 127:139 hemagglutinin and neuraminidase glycoproteins 95:139 hemagglutinin and neuraminidase glycoproteins 95:139 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 69 theme glycoforms 251:260 arg1 analyses 225:232 precise analyses 217:232 precise analyses of site-specific glycoforms in these proteins 217:278 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 69 theme glycoforms 251:260 arg1 Analyses 15:22 Glycoproteomic Analyses 0:22 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties 0:210 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 2 70 theme interaction 662:672 arg1 chromatography 681:694 the hydrophilic interaction liquid chromatography 646:694 the hydrophilic interaction liquid chromatography column enrichment 646:712 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 0 71 theme neuraminidase 113:125 arg1 glycoproteins 127:139 hemagglutinin and neuraminidase glycoproteins 95:139 hemagglutinin and neuraminidase glycoproteins 95:139 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 2 72 gly glycopeptides 820:832 arg2 glycopeptides 820:832 low-abundance glycopeptides 806:832 low-abundance glycopeptides 806:832 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 2 73 theme similar 723:729 arg1 coverage 744:751 similar glycopeptide coverage 723:751 similar glycopeptide coverage 723:751 Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. 36480915 6 74 dep quantify 1441:1448 arg1 facilitate 1535:1544 facilitate 1535:1544 facilitate influenza vaccine development and production 1535:1589 In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production. 36480915 0 75 theme Influenza 27:35 arg1 Viruses 39:45 Influenza A Viruses 27:45 Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties 27:210 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 4 76 theme N483 1108:1111 arg1 glycans 1135:1141 N483 but only high-mannose glycans 1108:1141 N483 but only high-mannose glycans 1108:1141 Results showed that hemagglutinin for both viruses had complex N-glycans at N22, N38, N240, and N483 but only high-mannose glycans at N411 and, however, that the type and quantities of glycans were distinct between these viruses. 36480915 0 77 theme Viruses 39:45 arg1 analyses 225:232 precise analyses 217:232 precise analyses of site-specific glycoforms in these proteins 217:278 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 0 77 theme Viruses 39:45 arg1 Analyses 15:22 Glycoproteomic Analyses 0:22 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties 0:210 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 5 78 theme cross 1254:1258 arg1 CCS 1269:1271 CCS 1269:1271 CCS 1269:1271 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 5 78 theme cross 1254:1258 arg1 section 1260:1266 Collisional cross section 1242:1266 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data 1242:1343 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 0 79 theme timsTOF 53:59 arg1 Pro 61:63 timsTOF Pro 53:63 timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties 53:210 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 4 80 contain had 1063:1065 arg2 N-glycans 1075:1083 complex N-glycans 1067:1083 complex N-glycans 1067:1083 Results showed that hemagglutinin for both viruses had complex N-glycans at N22, N38, N240, and N483 but only high-mannose glycans at N411 and, however, that the type and quantities of glycans were distinct between these viruses. 36480915 4 80 contain had 1063:1065 arg1 hemagglutinin 1032:1044 hemagglutinin 1032:1044 hemagglutinin for both viruses 1032:1061 Results showed that hemagglutinin for both viruses had complex N-glycans at N22, N38, N240, and N483 but only high-mannose glycans at N411 and, however, that the type and quantities of glycans were distinct between these viruses. 36480915 0 81 from analyses 225:232 arg1 proteins 271:278 these proteins 265:278 these proteins 265:278 Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS. N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. 36480915 4 82 dep type 1174:1177 arg1 the 1170:1172 the 1170:1172 the 1170:1172 Results showed that hemagglutinin for both viruses had complex N-glycans at N22, N38, N240, and N483 but only high-mannose glycans at N411 and, however, that the type and quantities of glycans were distinct between these viruses. 36480915 1 83 theme glycosylation 535:547 arg1 heterogeneity 504:516 heterogeneity 504:516 heterogeneity 504:516 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 1 83 theme glycosylation 535:547 arg1 abundance 490:498 abundance 490:498 abundance 490:498 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 5 84 gly glycopeptides 1388:1400 arg2 glycopeptides 1388:1400 the glycopeptides 1384:1400 the glycopeptides 1384:1400 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 36480915 1 85 theme influenza 553:561 arg1 glycoproteins 563:575 influenza glycoproteins 553:575 influenza glycoproteins 553:575 In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. 36480915 6 86 theme influenza 1546:1554 arg1 development 1564:1574 influenza vaccine development 1546:1574 influenza vaccine development 1546:1574 In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production. 36480915 5 87 theme ion 1290:1292 arg1 spectrometry 1303:1314 the ion mobility spectrometry 1286:1314 the ion mobility spectrometry from the timsTOF Pro MS data 1286:1343 Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. 35212163 5 0 theme sodium 814:819 arg1 colitis 837:843 dextran sodium sulfate-induced colitis 806:843 dextran sodium sulfate-induced colitis 806:843 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 5 0 theme sodium 814:819 arg1 model 854:858 a mouse model 846:858 a mouse model for inflammatory bowel disease 846:889 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 7 1 theme disease 1249:1255 arg1 shock 1283:1287 another inflammatory disease, lipopolysaccharide (LPS) shock 1228:1287 another inflammatory disease, lipopolysaccharide (LPS) shock 1228:1287 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 5 2 from arthritis 925:933 arg1 model 969:973 an experimental model 953:973 an experimental model for human rheumatoid arthritis 953:1004 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 5 2 from arthritis 925:933 arg1 mouse 946:950 the SKG mouse 938:950 the SKG mouse 938:950 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 1 3 theme interleukin 206:216 arg1 IL 219:220 interleukin (IL)-6 206:223 interleukin (IL)-6 206:223 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 9 4 theme targeted 1514:1521 arg1 therapies 1523:1531 targeted therapies 1514:1531 targeted therapies that inhibit cytokine receptor glycosylation 1514:1576 These results suggest that targeted therapies that inhibit cytokine receptor glycosylation are effective for treatment of various inflammatory diseases. 35212163 0 5 theme immunological 101:113 arg1 responses 115:123 immunological responses 101:123 immunological responses 101:123 2-Deoxy-d-glucose induces deglycosylation of proinflammatory cytokine receptors and strongly reduces immunological responses in mouse models of inflammation. 35212163 2 6 theme cytokine 441:448 arg1 receptors 450:458 cytokine receptors 441:458 cytokine receptors 441:458 Such therapies are mainly performed by injection of antibodies against cytokines or cytokine receptors. 35212163 4 7 theme downstream 718:727 arg1 signals 743:749 downstream intracellular signals 718:749 downstream intracellular signals that included Janus kinases 718:777 Aglycoforms of gp130 did not bind to IL-6 or activate downstream intracellular signals that included Janus kinases. 35212163 0 8 theme mouse 128:132 arg1 models 134:139 mouse models 128:139 mouse models of inflammation 128:155 2-Deoxy-d-glucose induces deglycosylation of proinflammatory cytokine receptors and strongly reduces immunological responses in mouse models of inflammation. 35212163 3 9 theme N-linked 613:620 arg1 glycosylation 622:634 N-linked glycosylation 613:634 N-linked glycosylation of the IL-6 receptor gp130 613:661 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 3 10 theme cellular 572:579 arg1 responses 581:589 cellular responses 572:589 cellular responses to IL-6 572:597 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 9 11 theme inflammatory 1617:1628 arg1 diseases 1630:1637 various inflammatory diseases 1609:1637 various inflammatory diseases 1609:1637 These results suggest that targeted therapies that inhibit cytokine receptor glycosylation are effective for treatment of various inflammatory diseases. 35212163 7 12 theme inflammatory 1236:1247 arg1 lipopolysaccharide 1258:1275 lipopolysaccharide 1258:1275 lipopolysaccharide (LPS) 1258:1281 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 7 12 theme inflammatory 1236:1247 arg1 disease 1249:1255 another inflammatory disease 1228:1255 another inflammatory disease 1228:1255 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 4 13 theme intracellular 729:741 arg1 signals 743:749 downstream intracellular signals 718:749 downstream intracellular signals that included Janus kinases 718:777 Aglycoforms of gp130 did not bind to IL-6 or activate downstream intracellular signals that included Janus kinases. 35212163 1 14 theme major 270:274 arg1 advancements 276:287 major advancements 270:287 major advancements in treating inflammatory diseases 270:321 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 1 14 theme major 270:274 arg1 arthritis 346:354 rheumatoid arthritis 335:354 especially rheumatoid arthritis 324:354 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 1 14 theme major 270:274 arg1 therapies 188:196 Anti-proinflammatory cytokine therapies 158:196 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 158:264 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 4 15 gly Aglycoforms 664:674 arg1 gp130 679:683 gp130 679:683 gp130 679:683 Aglycoforms of gp130 did not bind to IL-6 or activate downstream intracellular signals that included Janus kinases. 35212163 3 16 theme inhibitor 500:508 arg1 2-DG 529:532 2-DG 529:532 2-DG 529:532 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 3 16 theme inhibitor 500:508 arg1 2-deoxy-d-glucose 510:526 the glycolytic inhibitor 2-deoxy-d-glucose 485:526 the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) 485:533 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 3 16 theme inhibitor 500:508 arg1 monosaccharide 545:558 a simple monosaccharide 536:558 a simple monosaccharide 536:558 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 8 17 theme LPS-induced 1363:1373 arg1 inflammation 1385:1396 LPS-induced pulmonary inflammation 1363:1396 LPS-induced pulmonary inflammation 1363:1396 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 8 17 theme LPS-induced 1363:1373 arg1 model 1401:1405 a model 1399:1405 a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19) 1399:1484 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 5 18 theme laminarin-induced 907:923 arg1 arthritis 925:933 laminarin-induced arthritis 907:933 laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis 907:1004 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 5 19 theme mouse 848:852 arg1 colitis 837:843 dextran sodium sulfate-induced colitis 806:843 dextran sodium sulfate-induced colitis 806:843 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 5 19 theme mouse 848:852 arg1 model 854:858 a mouse model 846:858 a mouse model for inflammatory bowel disease 846:889 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 3 20 link N-linked 613:620 arg1 glycosylation 622:634 N-linked glycosylation 613:634 N-linked glycosylation of the IL-6 receptor gp130 613:661 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 7 21 theme other 1119:1123 arg1 -γ 1188:1189 interferon -γ 1177:1189 interferon -γ 1177:1189 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 7 21 theme other 1119:1123 arg1 IL-1β 1166:1170 IL-1β 1166:1170 IL-1β 1166:1170 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 7 21 theme other 1119:1123 arg1 cytokines 1141:1149 other proinflammatory cytokines 1119:1149 other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ 1119:1189 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 7 21 theme other 1119:1123 arg1 TNF-α 1159:1163 TNF-α 1159:1163 TNF-α 1159:1163 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 2 22 theme antibodies 409:418 arg1 injection 396:404 injection 396:404 injection of antibodies against cytokines or cytokine receptors 396:458 Such therapies are mainly performed by injection of antibodies against cytokines or cytokine receptors. 35212163 9 23 theme cytokine 1546:1553 arg1 glycosylation 1564:1576 cytokine receptor glycosylation 1546:1576 cytokine receptor glycosylation 1546:1576 These results suggest that targeted therapies that inhibit cytokine receptor glycosylation are effective for treatment of various inflammatory diseases. 35212163 5 24 theme sulfate-induced 821:835 arg1 colitis 837:843 dextran sodium sulfate-induced colitis 806:843 dextran sodium sulfate-induced colitis 806:843 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 5 24 theme sulfate-induced 821:835 arg1 model 854:858 a mouse model 846:858 a mouse model for inflammatory bowel disease 846:889 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 7 25 theme proinflammatory 1125:1139 arg1 -γ 1188:1189 interferon -γ 1177:1189 interferon -γ 1177:1189 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 7 25 theme proinflammatory 1125:1139 arg1 IL-1β 1166:1170 IL-1β 1166:1170 IL-1β 1166:1170 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 7 25 theme proinflammatory 1125:1139 arg1 cytokines 1141:1149 other proinflammatory cytokines 1119:1149 other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ 1119:1189 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 7 25 theme proinflammatory 1125:1139 arg1 TNF-α 1159:1163 TNF-α 1159:1163 TNF-α 1159:1163 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 5 26 theme rheumatoid 985:994 arg1 arthritis 996:1004 human rheumatoid arthritis 979:1004 human rheumatoid arthritis 979:1004 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 8 27 theme pulmonary 1375:1383 arg1 inflammation 1385:1396 LPS-induced pulmonary inflammation 1363:1396 LPS-induced pulmonary inflammation 1363:1396 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 8 27 theme pulmonary 1375:1383 arg1 model 1401:1405 a model 1399:1405 a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19) 1399:1484 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 5 28 theme inflammatory 864:875 arg1 disease 883:889 inflammatory bowel disease 864:889 inflammatory bowel disease 864:889 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 8 29 theme coronavirus 1450:1460 arg1 disease 1462:1468 coronavirus disease 2019 1450:1473 coronavirus disease 2019 (COVID-19) 1450:1484 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 8 29 theme coronavirus 1450:1460 arg1 COVID-19 1476:1483 COVID-19 1476:1483 COVID-19 1476:1483 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 5 30 theme human 979:983 arg1 arthritis 996:1004 human rheumatoid arthritis 979:1004 human rheumatoid arthritis 979:1004 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 9 31 theme various 1609:1615 arg1 diseases 1630:1637 various inflammatory diseases 1609:1637 various inflammatory diseases 1609:1637 These results suggest that targeted therapies that inhibit cytokine receptor glycosylation are effective for treatment of various inflammatory diseases. 35212163 1 32 theme tumor 226:230 arg1 TNF 249:251 TNF 249:251 TNF 249:251 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 1 32 theme tumor 226:230 arg1 factor 241:246 tumor necrosis factor (TNF)-α 226:254 tumor necrosis factor (TNF)-α 226:254 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 5 33 theme bowel 877:881 arg1 disease 883:889 inflammatory bowel disease 864:889 inflammatory bowel disease 864:889 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 0 34 theme inflammation 144:155 arg1 models 134:139 mouse models 128:139 mouse models of inflammation 128:155 2-Deoxy-d-glucose induces deglycosylation of proinflammatory cytokine receptors and strongly reduces immunological responses in mouse models of inflammation. 35212163 9 35 theme receptor 1555:1562 arg1 glycosylation 1564:1576 cytokine receptor glycosylation 1546:1576 cytokine receptor glycosylation 1546:1576 These results suggest that targeted therapies that inhibit cytokine receptor glycosylation are effective for treatment of various inflammatory diseases. 35212163 1 36 theme necrosis 232:239 arg1 TNF 249:251 TNF 249:251 TNF 249:251 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 1 36 theme necrosis 232:239 arg1 factor 241:246 tumor necrosis factor (TNF)-α 226:254 tumor necrosis factor (TNF)-α 226:254 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 0 37 theme cytokine 61:68 arg1 receptors 70:78 proinflammatory cytokine receptors 45:78 proinflammatory cytokine receptors 45:78 2-Deoxy-d-glucose induces deglycosylation of proinflammatory cytokine receptors and strongly reduces immunological responses in mouse models of inflammation. 35212163 1 38 theme inflammatory 301:312 arg1 diseases 314:321 inflammatory diseases 301:321 inflammatory diseases 301:321 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 8 39 theme disease 1462:1468 arg1 syndrome 1438:1445 acute respiratory distress syndrome 1411:1445 acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19) 1411:1484 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 9 40 theme diseases 1630:1637 arg1 treatment 1596:1604 treatment 1596:1604 treatment of various inflammatory diseases 1596:1637 These results suggest that targeted therapies that inhibit cytokine receptor glycosylation are effective for treatment of various inflammatory diseases. 35212163 3 41 gly glycosylation 622:634 arg1 gp130 657:661 the IL-6 receptor gp130 639:661 the IL-6 receptor gp130 639:661 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 0 42 theme proinflammatory 45:59 arg1 receptors 70:78 proinflammatory cytokine receptors 45:78 proinflammatory cytokine receptors 45:78 2-Deoxy-d-glucose induces deglycosylation of proinflammatory cytokine receptors and strongly reduces immunological responses in mouse models of inflammation. 35212163 4 43 theme gp130 679:683 arg1 Aglycoforms 664:674 Aglycoforms 664:674 Aglycoforms of gp130 664:683 Aglycoforms of gp130 did not bind to IL-6 or activate downstream intracellular signals that included Janus kinases. 35212163 5 44 theme SKG 942:944 arg1 model 969:973 an experimental model 953:973 an experimental model for human rheumatoid arthritis 953:1004 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 5 44 theme SKG 942:944 arg1 mouse 946:950 the SKG mouse 938:950 the SKG mouse 938:950 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 0 45 gly deglycosylation 26:40 arg1 receptors 70:78 proinflammatory cytokine receptors 45:78 proinflammatory cytokine receptors 45:78 2-Deoxy-d-glucose induces deglycosylation of proinflammatory cytokine receptors and strongly reduces immunological responses in mouse models of inflammation. 35212163 5 46 theme experimental 956:967 arg1 model 969:973 an experimental model 953:973 an experimental model for human rheumatoid arthritis 953:1004 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 5 46 theme experimental 956:967 arg1 mouse 946:950 the SKG mouse 938:950 the SKG mouse 938:950 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 0 47 theme receptors 70:78 arg1 deglycosylation 26:40 deglycosylation 26:40 deglycosylation of proinflammatory cytokine receptors 26:78 2-Deoxy-d-glucose induces deglycosylation of proinflammatory cytokine receptors and strongly reduces immunological responses in mouse models of inflammation. 35212163 8 48 theme respiratory 1417:1427 arg1 syndrome 1438:1445 acute respiratory distress syndrome 1411:1445 acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19) 1411:1484 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 8 49 theme acute 1411:1415 arg1 syndrome 1438:1445 acute respiratory distress syndrome 1411:1445 acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19) 1411:1484 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 2 50 theme Such 357:360 arg1 therapies 362:370 Such therapies 357:370 Such therapies 357:370 Such therapies are mainly performed by injection of antibodies against cytokines or cytokine receptors. 35212163 1 51 theme rheumatoid 335:344 arg1 arthritis 346:354 rheumatoid arthritis 335:354 especially rheumatoid arthritis 324:354 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 1 51 theme rheumatoid 335:344 arg1 advancements 276:287 major advancements 270:287 major advancements in treating inflammatory diseases 270:321 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 7 52 theme interferon 1177:1186 arg1 -γ 1188:1189 interferon -γ 1177:1189 interferon -γ 1177:1189 We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. 35212163 3 53 theme gp130 657:661 arg1 glycosylation 622:634 N-linked glycosylation 613:634 N-linked glycosylation of the IL-6 receptor gp130 613:661 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 1 54 theme Anti-proinflammatory 158:177 arg1 advancements 276:287 major advancements 270:287 major advancements in treating inflammatory diseases 270:321 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 1 54 theme Anti-proinflammatory 158:177 arg1 therapies 188:196 Anti-proinflammatory cytokine therapies 158:196 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 158:264 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 8 55 theme distress 1429:1436 arg1 syndrome 1438:1445 acute respiratory distress syndrome 1411:1445 acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19) 1411:1484 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 1 56 theme cytokine 179:186 arg1 advancements 276:287 major advancements 270:287 major advancements in treating inflammatory diseases 270:321 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 1 56 theme cytokine 179:186 arg1 therapies 188:196 Anti-proinflammatory cytokine therapies 158:196 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 158:264 Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. 35212163 8 57 theme cytokine 1343:1350 arg1 storm 1352:1356 a cytokine storm 1341:1356 a cytokine storm 1341:1356 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 35212163 4 58 theme Janus 765:769 arg1 kinases 771:777 Janus kinases 765:777 Janus kinases 765:777 Aglycoforms of gp130 did not bind to IL-6 or activate downstream intracellular signals that included Janus kinases. 35212163 3 59 theme IL-6 643:646 arg1 gp130 657:661 the IL-6 receptor gp130 639:661 the IL-6 receptor gp130 639:661 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 3 60 theme glycolytic 489:498 arg1 2-DG 529:532 2-DG 529:532 2-DG 529:532 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 3 60 theme glycolytic 489:498 arg1 2-deoxy-d-glucose 510:526 the glycolytic inhibitor 2-deoxy-d-glucose 485:526 the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) 485:533 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 3 60 theme glycolytic 489:498 arg1 monosaccharide 545:558 a simple monosaccharide 536:558 a simple monosaccharide 536:558 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 3 61 theme simple 538:543 arg1 2-deoxy-d-glucose 510:526 the glycolytic inhibitor 2-deoxy-d-glucose 485:526 the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) 485:533 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 3 61 theme simple 538:543 arg1 monosaccharide 545:558 a simple monosaccharide 536:558 a simple monosaccharide 536:558 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 5 62 theme dextran 806:812 arg1 colitis 837:843 dextran sodium sulfate-induced colitis 806:843 dextran sodium sulfate-induced colitis 806:843 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 5 62 theme dextran 806:812 arg1 model 854:858 a mouse model 846:858 a mouse model for inflammatory bowel disease 846:889 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. 35212163 3 63 theme receptor 648:655 arg1 gp130 657:661 the IL-6 receptor gp130 639:661 the IL-6 receptor gp130 639:661 We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. 35212163 8 64 theme LPS 1318:1320 arg1 shock 1322:1326 LPS shock 1318:1326 LPS shock 1318:1326 Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). 36711084 4 0 theme mAb 865:867 arg1 2C4 869:871 the anti-Siglec-8 mAb 2C4 847:871 the anti-Siglec-8 mAb 2C4 847:871 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 6 1 theme NSANeuAc 1250:1257 arg1 ring 1242:1245 the sialoside ring 1228:1245 the sialoside ring of NSANeuAc 1228:1257 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 3 2 with mimetic 689:695 arg1 potential 706:714 the potential to suppress mast cell degranulation 702:750 the potential to suppress mast cell degranulation 702:750 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 5 3 theme spectroscopy 1166:1177 arg1 combination 1147:1157 a combination 1145:1157 a combination of NMR spectroscopy and X-ray crystallography 1145:1203 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 8 4 link N-linked 1732:1739 arg1 glycans 1741:1747 the N-linked glycans 1728:1747 the N-linked glycans present on the high-affinity receptor FcεRIα 1728:1792 Additionally, the specific interactions between Siglec-8 and the N-linked glycans present on the high-affinity receptor FcεRIα have also been explored by NMR. 36711084 3 5 theme molecular 546:554 arg1 features 568:575 the molecular recognition features 542:575 the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation 542:750 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 1 6 theme cell 274:277 arg1 degranulation 279:291 mast cell degranulation 269:291 mast cell degranulation 269:291 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 4 7 theme portion 836:842 arg1 structure 775:783 The three-dimensional structure 753:783 The three-dimensional structure 753:783 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 6 8 theme unique 1485:1490 arg1 loop 1497:1500 the unique G-G' loop 1481:1500 the unique G-G' loop 1481:1500 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 3 9 theme mast 728:731 arg1 degranulation 738:750 mast cell degranulation 728:750 mast cell degranulation 728:750 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 5 10 theme binding 1031:1037 arg1 mode 1039:1042 the binding mode 1027:1042 the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) 1027:1137 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 6 11 theme N-terminal 1461:1470 arg1 tail 1472:1475 the N-terminal tail 1457:1475 the N-terminal tail 1457:1475 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 1 12 theme inhibitory 198:207 arg1 receptor 209:216 an inhibitory receptor 195:216 an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands 195:367 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 12 theme inhibitory 198:207 arg1 lectin-8 172:179 Human sialic acid binding immunoglobulin-like lectin-8 126:179 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) 126:190 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 6 13 theme binding 1289:1295 arg1 pocket 1297:1302 the canonical sialyl binding pocket 1268:1302 the canonical sialyl binding pocket of the Siglec receptor family 1268:1332 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 8 14 theme specific 1685:1692 arg1 interactions 1694:1705 the specific interactions 1681:1705 the specific interactions between Siglec-8 and the N-linked glycans present on the high-affinity receptor FcεRIα 1681:1792 Additionally, the specific interactions between Siglec-8 and the N-linked glycans present on the high-affinity receptor FcεRIα have also been explored by NMR. 36711084 6 15 theme canonical 1272:1280 arg1 pocket 1297:1302 the canonical sialyl binding pocket 1268:1302 the canonical sialyl binding pocket of the Siglec receptor family 1268:1332 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 7 16 theme observed 1540:1547 arg1 affinity 1554:1561 the observed high affinity 1536:1561 the observed high affinity of this ligand 1536:1576 The results reveal the basis for the observed high affinity of this ligand and provide clues for the rational design of the next generation of Siglec-8 inhibitors. 36711084 6 17 from accommodation 1377:1389 arg1 patch 1441:1445 a nearby hydrophobic patch 1420:1445 a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop 1420:1500 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 1 18 theme sialic 132:137 arg1 receptor 209:216 an inhibitory receptor 195:216 an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands 195:367 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 18 theme sialic 132:137 arg1 Siglec-8 182:189 Siglec-8 182:189 Siglec-8 182:189 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 18 theme sialic 132:137 arg1 lectin-8 172:179 Human sialic acid binding immunoglobulin-like lectin-8 126:179 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) 126:190 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 7 19 theme inhibitors 1655:1664 arg1 generation 1632:1641 the next generation 1623:1641 the next generation of Siglec-8 inhibitors 1623:1664 The results reveal the basis for the observed high affinity of this ligand and provide clues for the rational design of the next generation of Siglec-8 inhibitors. 36711084 4 20 theme recognition 955:965 arg1 domain 985:990 V-type Ig domain 975:990 V-type Ig domain 975:990 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 4 20 theme recognition 955:965 arg1 domain 967:972 the carbohydrate recognition domain 938:972 the carbohydrate recognition domain (V-type Ig domain) on Siglec-8 938:1003 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 6 21 theme high 1347:1350 arg1 affinity 1352:1359 the high affinity 1343:1359 the high affinity 1343:1359 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 5 22 theme sialic 1079:1084 arg1 acid 1086:1089 its sialic acid 1075:1089 its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) 1075:1137 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 3 23 theme mAb 617:619 arg1 lirentelimab 621:632 the mAb lirentelimab 613:632 the mAb lirentelimab (2C4, under clinical development) 613:666 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 8 24 theme N-linked 1732:1739 arg1 glycans 1741:1747 the N-linked glycans 1728:1747 the N-linked glycans present on the high-affinity receptor FcεRIα 1728:1792 Additionally, the specific interactions between Siglec-8 and the N-linked glycans present on the high-affinity receptor FcεRIα have also been explored by NMR. 36711084 1 25 theme binding 144:150 arg1 receptor 209:216 an inhibitory receptor 195:216 an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands 195:367 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 25 theme binding 144:150 arg1 Siglec-8 182:189 Siglec-8 182:189 Siglec-8 182:189 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 25 theme binding 144:150 arg1 lectin-8 172:179 Human sialic acid binding immunoglobulin-like lectin-8 126:179 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) 126:190 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 2 26 theme allergic 485:492 arg1 inflammation 501:512 allergic airway inflammation 485:512 allergic airway inflammation 485:512 Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. 36711084 0 27 theme High-Affinity 65:77 arg1 Analogue 89:96 a High-Affinity Sialoside Analogue 63:96 a High-Affinity Sialoside Analogue 63:96 Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody. 36711084 5 28 theme ligand 1091:1096 arg1 analogue 1063:1070 a high-affinity analogue 1047:1070 a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) 1047:1137 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 8 29 theme present 1749:1755 arg1 glycans 1741:1747 the N-linked glycans 1728:1747 the N-linked glycans present on the high-affinity receptor FcεRIα 1728:1792 Additionally, the specific interactions between Siglec-8 and the N-linked glycans present on the high-affinity receptor FcεRIα have also been explored by NMR. 36711084 7 30 theme next 1627:1630 arg1 generation 1632:1641 the next generation 1623:1641 the next generation of Siglec-8 inhibitors 1623:1664 The results reveal the basis for the observed high affinity of this ligand and provide clues for the rational design of the next generation of Siglec-8 inhibitors. 36711084 0 31 from Structures 0:9 arg1 Complex 50:56 Complex 50:56 Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody 50:123 Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody. 36711084 4 32 theme three-dimensional 757:773 arg1 structure 775:783 The three-dimensional structure 753:783 The three-dimensional structure 753:783 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 6 33 theme family 1327:1332 arg1 pocket 1297:1302 the canonical sialyl binding pocket 1268:1302 the canonical sialyl binding pocket of the Siglec receptor family 1268:1332 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 5 34 theme high-affinity 1049:1061 arg1 analogue 1063:1070 a high-affinity analogue 1047:1070 a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) 1047:1137 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 5 35 theme X-ray 1183:1187 arg1 crystallography 1189:1203 X-ray crystallography 1183:1203 X-ray crystallography 1183:1203 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 8 36 theme receptor 1778:1785 arg1 FcεRIα 1787:1792 the high-affinity receptor FcεRIα 1760:1792 the high-affinity receptor FcεRIα 1760:1792 Additionally, the specific interactions between Siglec-8 and the N-linked glycans present on the high-affinity receptor FcεRIα have also been explored by NMR. 36711084 7 37 theme rational 1604:1611 arg1 design 1613:1618 the rational design 1600:1618 the rational design of the next generation of Siglec-8 inhibitors 1600:1664 The results reveal the basis for the observed high affinity of this ligand and provide clues for the rational design of the next generation of Siglec-8 inhibitors. 36711084 6 38 theme NSA 1398:1400 arg1 group 1411:1415 the NSA aromatic group 1394:1415 the NSA aromatic group 1394:1415 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 2 39 theme inflammatory 433:444 arg1 responses 446:454 inflammatory responses 433:454 inflammatory responses 433:454 Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. 36711084 4 40 theme Ig 982:983 arg1 domain 985:990 V-type Ig domain 975:990 V-type Ig domain 975:990 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 4 40 theme Ig 982:983 arg1 domain 967:972 the carbohydrate recognition domain 938:972 the carbohydrate recognition domain (V-type Ig domain) on Siglec-8 938:1003 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 3 41 theme clinical 646:653 arg1 development 655:665 clinical development 646:665 clinical development 646:665 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 4 42 theme binding 822:828 arg1 portion 836:842 the fragment antigen binding (Fab) portion 801:842 the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4 801:871 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 2 43 theme critical 402:409 arg1 regulator 420:428 a critical negative regulator 400:428 a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation 400:512 Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. 36711084 0 44 theme Receptor 29:36 arg1 Siglec-8 38:45 the Inhibitory Receptor Siglec-8 14:45 the Inhibitory Receptor Siglec-8 14:45 Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody. 36711084 1 45 theme specific 309:316 arg1 mAbs 341:344 mAbs 341:344 mAbs 341:344 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 45 theme specific 309:316 arg1 antibodies 329:338 specific monoclonal antibodies 309:338 specific monoclonal antibodies (mAbs) 309:345 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 2 46 theme airway 494:499 arg1 inflammation 501:512 allergic airway inflammation 485:512 allergic airway inflammation 485:512 Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. 36711084 4 47 theme Fab 831:833 arg1 portion 836:842 the fragment antigen binding (Fab) portion 801:842 the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4 801:871 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 5 48 theme crystallography 1189:1203 arg1 combination 1147:1157 a combination 1145:1157 a combination of NMR spectroscopy and X-ray crystallography 1145:1203 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 1 49 gly sialylated 350:359 arg1 ligands 361:367 sialylated ligands 350:367 sialylated ligands 350:367 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 4 50 theme fragment 805:812 arg1 portion 836:842 the fragment antigen binding (Fab) portion 801:842 the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4 801:871 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 6 51 theme hydrophobic 1429:1439 arg1 patch 1441:1445 a nearby hydrophobic patch 1420:1445 a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop 1420:1500 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 2 52 from regulator 420:428 arg1 diseases 467:474 diverse diseases 459:474 diverse diseases 459:474 Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. 36711084 2 52 from regulator 420:428 arg1 inflammation 501:512 allergic airway inflammation 485:512 allergic airway inflammation 485:512 Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. 36711084 5 53 theme NMR 1162:1164 arg1 spectroscopy 1166:1177 NMR spectroscopy 1162:1177 NMR spectroscopy 1162:1177 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 4 54 theme anti-Siglec-8 851:863 arg1 2C4 869:871 the anti-Siglec-8 mAb 2C4 847:871 the anti-Siglec-8 mAb 2C4 847:871 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 6 55 theme group 1411:1415 arg1 accommodation 1377:1389 the accommodation 1373:1389 the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop 1373:1500 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 1 56 theme mast 269:272 arg1 degranulation 279:291 mast cell degranulation 269:291 mast cell degranulation 269:291 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 4 57 theme 2C4 869:871 arg1 Siglec-8 788:795 Siglec-8 788:795 Siglec-8 788:795 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 4 57 theme 2C4 869:871 arg1 portion 836:842 the fragment antigen binding (Fab) portion 801:842 the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4 801:871 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 8 58 attach present 1749:1755 arg2 glycans 1741:1747 the N-linked glycans 1728:1747 the N-linked glycans present on the high-affinity receptor FcεRIα 1728:1792 Additionally, the specific interactions between Siglec-8 and the N-linked glycans present on the high-affinity receptor FcεRIα have also been explored by NMR. 36711084 8 58 attach present 1749:1755 arg1 FcεRIα 1787:1792 the high-affinity receptor FcεRIα 1760:1792 the high-affinity receptor FcεRIα 1760:1792 Additionally, the specific interactions between Siglec-8 and the N-linked glycans present on the high-affinity receptor FcεRIα have also been explored by NMR. 36711084 6 59 theme sialoside 1232:1240 arg1 ring 1242:1245 the sialoside ring 1228:1245 the sialoside ring of NSANeuAc 1228:1257 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 6 60 theme G-G 1492:1494 arg1 loop 1497:1500 the unique G-G' loop 1481:1500 the unique G-G' loop 1481:1500 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 7 61 theme ligand 1571:1576 arg1 affinity 1554:1561 the observed high affinity 1536:1561 the observed high affinity of this ligand 1536:1576 The results reveal the basis for the observed high affinity of this ligand and provide clues for the rational design of the next generation of Siglec-8 inhibitors. 36711084 3 62 theme recognition 556:566 arg1 features 568:575 the molecular recognition features 542:575 the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation 542:750 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 3 63 theme cell 733:736 arg1 degranulation 738:750 mast cell degranulation 728:750 mast cell degranulation 728:750 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 3 64 theme Siglec-8 599:606 arg1 interaction 584:594 the interaction 580:594 the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation 580:750 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 3 65 dep lirentelimab 621:632 arg1 2C4 635:637 2C4 635:637 2C4 635:637 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 7 66 theme high 1549:1552 arg1 affinity 1554:1561 the observed high affinity 1536:1561 the observed high affinity of this ligand 1536:1576 The results reveal the basis for the observed high affinity of this ligand and provide clues for the rational design of the next generation of Siglec-8 inhibitors. 36711084 6 67 theme sialyl 1282:1287 arg1 pocket 1297:1302 the canonical sialyl binding pocket 1268:1302 the canonical sialyl binding pocket of the Siglec receptor family 1268:1332 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 3 68 theme interaction 584:594 arg1 features 568:575 the molecular recognition features 542:575 the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation 542:750 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 1 69 theme Human 126:130 arg1 receptor 209:216 an inhibitory receptor 195:216 an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands 195:367 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 69 theme Human 126:130 arg1 Siglec-8 182:189 Siglec-8 182:189 Siglec-8 182:189 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 69 theme Human 126:130 arg1 lectin-8 172:179 Human sialic acid binding immunoglobulin-like lectin-8 126:179 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) 126:190 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 4 70 theme X-ray 884:888 arg1 crystallography 890:904 X-ray crystallography 884:904 X-ray crystallography 884:904 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 1 71 theme acid 139:142 arg1 receptor 209:216 an inhibitory receptor 195:216 an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands 195:367 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 71 theme acid 139:142 arg1 Siglec-8 182:189 Siglec-8 182:189 Siglec-8 182:189 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 71 theme acid 139:142 arg1 lectin-8 172:179 Human sialic acid binding immunoglobulin-like lectin-8 126:179 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) 126:190 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 4 72 theme carbohydrate 942:953 arg1 domain 985:990 V-type Ig domain 975:990 V-type Ig domain 975:990 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 4 72 theme carbohydrate 942:953 arg1 domain 967:972 the carbohydrate recognition domain 938:972 the carbohydrate recognition domain (V-type Ig domain) on Siglec-8 938:1003 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 0 73 theme Sialoside 79:87 arg1 Analogue 89:96 a High-Affinity Sialoside Analogue 63:96 a High-Affinity Sialoside Analogue 63:96 Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody. 36711084 5 74 theme acid 1086:1089 arg1 ligand 1091:1096 its sialic acid ligand 1075:1096 its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) 1075:1137 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 1 75 theme immunoglobulin-like 152:170 arg1 receptor 209:216 an inhibitory receptor 195:216 an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands 195:367 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 75 theme immunoglobulin-like 152:170 arg1 Siglec-8 182:189 Siglec-8 182:189 Siglec-8 182:189 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 75 theme immunoglobulin-like 152:170 arg1 lectin-8 172:179 Human sialic acid binding immunoglobulin-like lectin-8 126:179 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) 126:190 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 7 76 theme Siglec-8 1646:1653 arg1 inhibitors 1655:1664 Siglec-8 inhibitors 1646:1664 Siglec-8 inhibitors 1646:1664 The results reveal the basis for the observed high affinity of this ligand and provide clues for the rational design of the next generation of Siglec-8 inhibitors. 36711084 3 77 with interaction 584:594 arg1 lirentelimab 621:632 the mAb lirentelimab 613:632 the mAb lirentelimab (2C4, under clinical development) 613:666 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 3 77 with interaction 584:594 arg1 sialoside 679:687 a sialoside 677:687 a sialoside mimetic with the potential to suppress mast cell degranulation 677:750 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 1 78 theme sialylated 350:359 arg1 ligands 361:367 sialylated ligands 350:367 sialylated ligands 350:367 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 7 79 theme generation 1632:1641 arg1 design 1613:1618 the rational design 1600:1618 the rational design of the next generation of Siglec-8 inhibitors 1600:1664 The results reveal the basis for the observed high affinity of this ligand and provide clues for the rational design of the next generation of Siglec-8 inhibitors. 36711084 0 80 theme Therapeutic 104:114 arg1 Antibody 116:123 a Therapeutic Antibody 102:123 a Therapeutic Antibody 102:123 Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody. 36711084 5 81 theme analogue 1063:1070 arg1 mode 1039:1042 the binding mode 1027:1042 the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) 1027:1137 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 1 82 theme eosinophil 232:241 arg1 apoptosis 243:251 eosinophil apoptosis 232:251 eosinophil apoptosis 232:251 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 6 83 theme receptor 1318:1325 arg1 family 1327:1332 the Siglec receptor family 1307:1332 the Siglec receptor family 1307:1332 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 6 84 theme aromatic 1402:1409 arg1 group 1411:1415 the NSA aromatic group 1394:1415 the NSA aromatic group 1394:1415 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 8 85 theme high-affinity 1764:1776 arg1 FcεRIα 1787:1792 the high-affinity receptor FcεRIα 1760:1792 the high-affinity receptor FcεRIα 1760:1792 Additionally, the specific interactions between Siglec-8 and the N-linked glycans present on the high-affinity receptor FcεRIα have also been explored by NMR. 36711084 2 86 theme responses 446:454 arg1 regulator 420:428 a critical negative regulator 400:428 a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation 400:512 Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. 36711084 5 87 dep ligand 1091:1096 arg1 NSANeuAc 1129:1136 NSANeuAc 1129:1136 NSANeuAc 1129:1136 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 5 87 dep ligand 1091:1096 arg1 9-N-napthylsufonimide-Neu5Ac 1099:1126 9-N-napthylsufonimide-Neu5Ac 1099:1126 9-N-napthylsufonimide-Neu5Ac 1099:1126 We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. 36711084 0 88 theme Inhibitory 18:27 arg1 Siglec-8 38:45 the Inhibitory Receptor Siglec-8 14:45 the Inhibitory Receptor Siglec-8 14:45 Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody. 36711084 2 89 theme negative 411:418 arg1 regulator 420:428 a critical negative regulator 400:428 a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation 400:512 Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. 36711084 0 90 theme Siglec-8 38:45 arg1 Structures 0:9 Structures 0:9 Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody. 0:124 Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody. 36711084 4 91 theme V-type 975:980 arg1 domain 985:990 V-type Ig domain 975:990 V-type Ig domain 975:990 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 4 91 theme V-type 975:980 arg1 domain 967:972 the carbohydrate recognition domain 938:972 the carbohydrate recognition domain (V-type Ig domain) on Siglec-8 938:1003 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 4 92 theme antigen 814:820 arg1 portion 836:842 the fragment antigen binding (Fab) portion 801:842 the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4 801:871 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 6 93 theme Siglec 1311:1316 arg1 family 1327:1332 the Siglec receptor family 1307:1332 the Siglec receptor family 1307:1332 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 36711084 1 94 theme monoclonal 318:327 arg1 mAbs 341:344 mAbs 341:344 mAbs 341:344 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 1 94 theme monoclonal 318:327 arg1 antibodies 329:338 specific monoclonal antibodies 309:338 specific monoclonal antibodies (mAbs) 309:345 Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. 36711084 2 95 theme diverse 459:465 arg1 diseases 467:474 diverse diseases 459:474 diverse diseases 459:474 Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. 36711084 2 95 theme diverse 459:465 arg1 inflammation 501:512 allergic airway inflammation 485:512 allergic airway inflammation 485:512 Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. 36711084 4 96 theme Siglec-8 788:795 arg1 structure 775:783 The three-dimensional structure 753:783 The three-dimensional structure 753:783 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 0 97 with Complex 50:56 arg1 Antibody 116:123 a Therapeutic Antibody 102:123 a Therapeutic Antibody 102:123 Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody. 36711084 0 97 with Complex 50:56 arg1 Analogue 89:96 a High-Affinity Sialoside Analogue 63:96 a High-Affinity Sialoside Analogue 63:96 Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody. 36711084 4 98 from domain 967:972 arg1 Siglec-8 996:1003 Siglec-8 996:1003 Siglec-8 996:1003 The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. 36711084 3 99 theme mimetic 689:695 arg1 sialoside 679:687 a sialoside 677:687 a sialoside mimetic with the potential to suppress mast cell degranulation 677:750 Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. 36711084 6 100 theme nearby 1422:1427 arg1 patch 1441:1445 a nearby hydrophobic patch 1420:1445 a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop 1420:1500 Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G-G' loop. 35752106 7 0 theme fucosylation 1227:1238 arg1 levels 1240:1245 FINDINGS IgG Fc fucosylation levels 1211:1245 FINDINGS IgG Fc fucosylation levels 1211:1245 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 6 1 used used 1005:1008 arg2 assay 996:1000 the first assay 986:1000 the first assay 986:1000 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 3 2 from immunopathologies 458:474 arg1 diseases 490:497 alloimmune diseases 479:497 alloimmune diseases 479:497 Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. 35752106 2 3 theme natural 333:339 arg1 killer 341:346 natural killer 333:346 natural killer (NK) 333:351 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 2 3 theme natural 333:339 arg1 NK 349:350 NK 349:350 NK 349:350 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 2 4 from Absence 194:200 arg1 glycan 245:250 the highly conserved N-linked glycan 215:250 the highly conserved N-linked glycan in the IgG Fc domain 215:271 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 7 5 from levels 1240:1245 arg1 responses 1305:1313 COVID-19 responses 1296:1313 COVID-19 responses to the spike (S) antigen 1296:1338 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 4 6 theme sophisticated 575:587 arg1 skills 678:683 extensive analytical skills 657:683 extensive analytical skills 657:683 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35752106 4 6 theme sophisticated 575:587 arg1 spectrometry 632:643 liquid chromatography-mass spectrometry 605:643 liquid chromatography-mass spectrometry (LC-MS) 605:651 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35752106 4 6 theme sophisticated 575:587 arg1 methods 589:595 sophisticated methods 575:595 sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories 575:727 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35752106 3 7 theme dengue 513:518 arg1 immunopathologies 458:474 immunopathologies 458:474 immunopathologies in alloimmune diseases 458:497 Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. 35752106 3 7 theme dengue 513:518 arg1 fever 520:524 dengue fever 513:524 dengue fever 513:524 Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. 35752106 9 8 theme IgG 1646:1648 arg1 fucosylation 1653:1664 relative and absolute IgG Fc fucosylation 1624:1664 relative and absolute IgG Fc fucosylation 1624:1664 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 6 9 theme IgG 1173:1175 arg1 ELISA 1203:1207 FcγR-IgG ELISA 1194:1207 FcγR-IgG ELISA 1194:1207 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 6 9 theme IgG 1173:1175 arg1 fucosylation 1180:1191 the IgG Fc fucosylation 1169:1191 the IgG Fc fucosylation (FcγR-IgG ELISA) 1169:1208 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 2 10 theme IgG 259:261 arg1 domain 266:271 the IgG Fc domain 255:271 the IgG Fc domain 255:271 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 7 11 dep correlated 1341:1350 arg1 R2=0.93 1395:1401 R2=0.93 1395:1401 R2=0.93 1395:1401 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 7 12 theme linear 1376:1381 arg1 regression 1383:1392 simple linear regression 1369:1392 simple linear regression 1369:1392 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 4 13 theme analytical 667:676 arg1 skills 678:683 extensive analytical skills 657:683 extensive analytical skills 657:683 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35752106 6 14 theme first 990:994 arg1 assay 996:1000 the first assay 986:1000 the first assay 986:1000 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 6 15 theme IgG 1152:1154 arg1 quantity 1156:1163 the IgG quantity 1148:1163 the IgG quantity 1148:1163 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 7 16 dep R2=0.93 1395:1401 arg1 p < 0.0001 1404:1413 p < 0.0001 1404:1413 p < 0.0001 1404:1413 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 6 17 theme two-tier 964:971 arg1 immunoassay 973:983 a two-tier immunoassay 962:983 a two-tier immunoassay 962:983 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 6 17 theme two-tier 964:971 arg1 FEASI 953:957 FEASI 953:957 FEASI 953:957 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 9 18 theme IgG 1707:1709 arg1 binding 1679:1685 binding 1679:1685 binding of antigen-specific IgG to FcγR 1679:1717 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 8 19 gly quantify 1451:1458 arg1 plasma 1513:1518 COVID-19 convalescent plasma 1491:1518 COVID-19 convalescent plasma which was independently validated by LC-MS 1491:1561 The FEASI method was then used to quantify IgG levels and fucosylation in COVID-19 convalescent plasma which was independently validated by LC-MS. 35752106 6 20 theme FcγR-IgG 1194:1201 arg1 ELISA 1203:1207 FcγR-IgG ELISA 1194:1207 FcγR-IgG ELISA 1194:1207 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 6 20 theme FcγR-IgG 1194:1201 arg1 fucosylation 1180:1191 the IgG Fc fucosylation 1169:1191 the IgG Fc fucosylation (FcγR-IgG ELISA) 1169:1208 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 7 21 theme Fc 1224:1225 arg1 levels 1240:1245 FINDINGS IgG Fc fucosylation levels 1211:1245 FINDINGS IgG Fc fucosylation levels 1211:1245 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 2 22 theme N-linked 236:243 arg1 glycan 245:250 the highly conserved N-linked glycan 215:250 the highly conserved N-linked glycan in the IgG Fc domain 215:271 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 6 23 theme antigen-specific 1022:1037 arg1 IgG 1039:1041 antigen-specific IgG 1022:1041 antigen-specific IgG (IgG ELISA) 1022:1053 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 6 23 theme antigen-specific 1022:1037 arg1 ELISA 1048:1052 IgG ELISA 1044:1052 IgG ELISA 1044:1052 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 5 24 theme immunosorbent 792:804 arg1 ELISA 813:817 ELISA 813:817 ELISA 813:817 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 5 24 theme immunosorbent 792:804 arg1 assay 806:810 the Fucose-sensitive Enzyme-linked immunosorbent assay 757:810 the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses 757:950 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 1 25 theme Fc 173:174 arg1 FcγR 187:190 FcγR 187:190 FcγR 187:190 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 1 25 theme Fc 173:174 arg1 receptors 176:184 IgG Fc receptors 169:184 IgG Fc receptors (FcγR) 169:191 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 8 26 theme IgG 1460:1462 arg1 levels 1464:1469 IgG levels 1460:1469 IgG levels 1460:1469 The FEASI method was then used to quantify IgG levels and fucosylation in COVID-19 convalescent plasma which was independently validated by LC-MS. 35752106 1 27 theme Immunoglobulin 80:93 arg1 G 95:95 BACKGROUND Immunoglobulin G 69:95 BACKGROUND Immunoglobulin G (IgG) antibodies 69:112 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 1 27 theme Immunoglobulin 80:93 arg1 IgG 98:100 IgG 98:100 IgG 98:100 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 9 28 theme diagnostic 1765:1774 arg1 laboratories 1789:1800 all diagnostic and research laboratories 1761:1800 all diagnostic and research laboratories 1761:1800 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 7 29 theme spike 1322:1326 arg1 antigen 1332:1338 the spike (S) antigen 1318:1338 the spike (S) antigen 1318:1338 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 9 30 theme research 1780:1787 arg1 laboratories 1789:1800 all diagnostic and research laboratories 1761:1800 all diagnostic and research laboratories 1761:1800 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 2 31 theme cell 353:356 arg1 FcγRs 358:362 cell FcγRs 353:362 cell FcγRs 353:362 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 5 32 theme Antigen-Specific 824:839 arg1 FEASI 846:850 FEASI 846:850 FEASI 846:850 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 5 32 theme Antigen-Specific 824:839 arg1 IgG 841:843 Antigen-Specific IgG 824:843 Antigen-Specific IgG (FEASI) 824:851 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 5 32 theme Antigen-Specific 824:839 arg1 immunoassay 857:867 an immunoassay 854:867 an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses 854:950 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 2 33 from glycan 245:250 arg1 domain 266:271 the IgG Fc domain 255:271 the IgG Fc domain 255:271 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 8 34 theme convalescent 1500:1511 arg1 plasma 1513:1518 COVID-19 convalescent plasma 1491:1518 COVID-19 convalescent plasma which was independently validated by LC-MS 1491:1561 The FEASI method was then used to quantify IgG levels and fucosylation in COVID-19 convalescent plasma which was independently validated by LC-MS. 35752106 7 35 theme COVID-19 1296:1303 arg1 responses 1305:1313 COVID-19 responses 1296:1313 COVID-19 responses to the spike (S) antigen 1296:1338 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 10 36 dep 01 1916:1917 arg1 0021 1923:1926 201 0021 1919:1926 201 0021 1919:1926 FUNDING This work was funded by the Stichting Sanquin Bloedvoorziening (PPOC 19-08 and SQI00041) and ZonMW 10430 01 201 0021. 35752106 0 37 theme antigen-specific 34:49 arg1 fucosylation 55:66 antigen-specific IgG fucosylation 34:66 antigen-specific IgG fucosylation 34:66 Immunoassay for quantification of antigen-specific IgG fucosylation. 35752106 9 38 theme INTERPRETATION 1564:1577 arg1 FEASI 1579:1583 INTERPRETATION FEASI 1564:1583 INTERPRETATION FEASI 1564:1583 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 9 39 theme high-throughput 1724:1738 arg1 manner 1740:1745 a high-throughput manner 1722:1745 a high-throughput manner accessible to all diagnostic and research laboratories 1722:1800 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 0 40 theme fucosylation 55:66 arg1 quantification 16:29 quantification 16:29 quantification of antigen-specific IgG fucosylation 16:66 Immunoassay for quantification of antigen-specific IgG fucosylation. 35752106 7 41 dep spike 1322:1326 arg1 S 1329:1329 S 1329:1329 S 1329:1329 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 5 42 theme Fucose-sensitive 761:776 arg1 ELISA 813:817 ELISA 813:817 ELISA 813:817 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 5 42 theme Fucose-sensitive 761:776 arg1 assay 806:810 the Fucose-sensitive Enzyme-linked immunosorbent assay 757:810 the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses 757:950 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 3 43 theme alloimmune 479:488 arg1 diseases 490:497 alloimmune diseases 479:497 alloimmune diseases 479:497 Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. 35752106 5 44 theme capable 869:875 arg1 IgG 841:843 Antigen-Specific IgG 824:843 Antigen-Specific IgG (FEASI) 824:851 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 5 44 theme capable 869:875 arg1 immunoassay 857:867 an immunoassay 854:867 an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses 854:950 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 0 45 dep Immunoassay 0:10 arg1 quantification 16:29 quantification 16:29 quantification of antigen-specific IgG fucosylation 16:66 Immunoassay for quantification of antigen-specific IgG fucosylation. 35752106 2 46 theme killer 341:346 arg1 activation 307:316 activation 307:316 activation of myeloid and natural killer (NK) cell FcγRs 307:362 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 2 46 theme killer 341:346 arg1 binding 295:301 IgG binding 291:301 IgG binding 291:301 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 9 47 theme relative 1624:1631 arg1 fucosylation 1653:1664 relative and absolute IgG Fc fucosylation 1624:1664 relative and absolute IgG Fc fucosylation 1624:1664 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 6 48 theme binding-dependent 1088:1104 arg1 readout 1106:1112 FcγRIIIa binding-dependent readout 1079:1112 FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA) 1079:1208 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 9 49 theme absolute 1637:1644 arg1 fucosylation 1653:1664 relative and absolute IgG Fc fucosylation 1624:1664 relative and absolute IgG Fc fucosylation 1624:1664 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 6 50 theme Fc 1177:1178 arg1 ELISA 1203:1207 FcγR-IgG ELISA 1194:1207 FcγR-IgG ELISA 1194:1207 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 6 50 theme Fc 1177:1178 arg1 fucosylation 1180:1191 the IgG Fc fucosylation 1169:1191 the IgG Fc fucosylation (FcγR-IgG ELISA) 1169:1208 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 2 51 theme Fc 263:264 arg1 domain 266:271 the IgG Fc domain 255:271 the IgG Fc domain 255:271 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 9 52 theme Fc 1650:1651 arg1 fucosylation 1653:1664 relative and absolute IgG Fc fucosylation 1624:1664 relative and absolute IgG Fc fucosylation 1624:1664 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 7 53 theme FINDINGS 1211:1218 arg1 levels 1240:1245 FINDINGS IgG Fc fucosylation levels 1211:1245 FINDINGS IgG Fc fucosylation levels 1211:1245 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 5 54 link Enzyme-linked 778:790 arg1 ELISA 813:817 ELISA 813:817 ELISA 813:817 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 5 54 link Enzyme-linked 778:790 arg1 assay 806:810 the Fucose-sensitive Enzyme-linked immunosorbent assay 757:810 the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses 757:950 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 4 55 theme extensive 657:665 arg1 skills 678:683 extensive analytical skills 657:683 extensive analytical skills 657:683 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35752106 2 56 theme IgG 291:293 arg1 binding 295:301 IgG binding 291:301 IgG binding 291:301 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 7 57 theme simple 1369:1374 arg1 regression 1383:1392 simple linear regression 1369:1392 simple linear regression 1369:1392 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 4 58 theme chromatography-mass 612:630 arg1 LC-MS 646:650 LC-MS 646:650 LC-MS 646:650 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35752106 4 58 theme chromatography-mass 612:630 arg1 spectrometry 632:643 liquid chromatography-mass spectrometry 605:643 liquid chromatography-mass spectrometry (LC-MS) 605:651 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35752106 2 59 theme conserved 226:234 arg1 glycan 245:250 the highly conserved N-linked glycan 215:250 the highly conserved N-linked glycan in the IgG Fc domain 215:271 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 9 60 theme antigen-specific 1690:1705 arg1 IgG 1707:1709 antigen-specific IgG 1690:1709 antigen-specific IgG 1690:1709 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 8 61 theme FEASI 1421:1425 arg1 method 1427:1432 The FEASI method 1417:1432 The FEASI method 1417:1432 The FEASI method was then used to quantify IgG levels and fucosylation in COVID-19 convalescent plasma which was independently validated by LC-MS. 35752106 8 62 used used 1443:1446 arg2 method 1427:1432 The FEASI method 1417:1432 The FEASI method 1417:1432 The FEASI method was then used to quantify IgG levels and fucosylation in COVID-19 convalescent plasma which was independently validated by LC-MS. 35752106 5 63 theme IgG 938:940 arg1 responses 942:950 IgG responses 938:950 IgG responses 938:950 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 4 64 theme specialized 704:714 arg1 laboratories 716:727 highly specialized laboratories 697:727 highly specialized laboratories 697:727 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35752106 1 65 theme immuno-protective 130:146 arg1 function 148:155 a crucial immuno-protective function 120:155 a crucial immuno-protective function mediated by IgG Fc receptors (FcγR) 120:191 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 6 66 theme IgG 1044:1046 arg1 IgG 1039:1041 antigen-specific IgG 1022:1041 antigen-specific IgG (IgG ELISA) 1022:1053 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 6 66 theme IgG 1044:1046 arg1 ELISA 1048:1052 IgG ELISA 1044:1052 IgG ELISA 1044:1052 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 7 67 theme IgG 1220:1222 arg1 levels 1240:1245 FINDINGS IgG Fc fucosylation levels 1211:1245 FINDINGS IgG Fc fucosylation levels 1211:1245 FINDINGS IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). 35752106 1 68 theme crucial 122:128 arg1 function 148:155 a crucial immuno-protective function 120:155 a crucial immuno-protective function mediated by IgG Fc receptors (FcγR) 120:191 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 5 69 dep METHODS 730:736 arg1 introduce 747:755 introduce 747:755 introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses 747:950 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 5 70 theme Enzyme-linked 778:790 arg1 ELISA 813:817 ELISA 813:817 ELISA 813:817 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 5 70 theme Enzyme-linked 778:790 arg1 assay 806:810 the Fucose-sensitive Enzyme-linked immunosorbent assay 757:810 the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses 757:950 METHODS Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. 35752106 1 71 theme IgG 169:171 arg1 FcγR 187:190 FcγR 187:190 FcγR 187:190 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 1 71 theme IgG 169:171 arg1 receptors 176:184 IgG Fc receptors 169:184 IgG Fc receptors (FcγR) 169:191 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 9 72 theme accessible 1747:1756 arg1 manner 1740:1745 a high-throughput manner 1722:1745 a high-throughput manner accessible to all diagnostic and research laboratories 1722:1800 INTERPRETATION FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. 35752106 2 73 link N-linked 236:243 arg1 glycan 245:250 the highly conserved N-linked glycan 215:250 the highly conserved N-linked glycan in the IgG Fc domain 215:271 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 3 74 gly afucosylated 374:385 arg1 IgG 387:389 afucosylated IgG 374:389 afucosylated IgG 374:389 Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. 35752106 1 75 theme BACKGROUND 69:78 arg1 G 95:95 BACKGROUND Immunoglobulin G 69:95 BACKGROUND Immunoglobulin G (IgG) antibodies 69:112 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 1 75 theme BACKGROUND 69:78 arg1 IgG 98:100 IgG 98:100 IgG 98:100 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 1 76 theme G 95:95 arg1 antibodies 103:112 BACKGROUND Immunoglobulin G (IgG) antibodies 69:112 BACKGROUND Immunoglobulin G (IgG) antibodies 69:112 BACKGROUND Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). 35752106 6 77 theme FcγRIIIa 1079:1086 arg1 readout 1106:1112 FcγRIIIa binding-dependent readout 1079:1112 FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA) 1079:1208 FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). 35752106 8 78 theme COVID-19 1491:1498 arg1 plasma 1513:1518 COVID-19 convalescent plasma 1491:1518 COVID-19 convalescent plasma which was independently validated by LC-MS 1491:1561 The FEASI method was then used to quantify IgG levels and fucosylation in COVID-19 convalescent plasma which was independently validated by LC-MS. 35752106 3 79 theme increased 403:411 arg1 protection 413:422 increased protection 403:422 increased protection (malaria and HIV) 403:440 Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. 35752106 3 79 theme increased 403:411 arg1 HIV 437:439 malaria and HIV 425:439 HIV 437:439 Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. 35752106 3 79 theme increased 403:411 arg1 malaria 425:431 malaria and HIV 425:439 malaria 425:431 Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. 35752106 4 80 theme IgG 539:541 arg1 fucosylation 543:554 IgG fucosylation 539:554 IgG fucosylation 539:554 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35752106 2 81 dep myeloid 321:327 arg1 FcγRs 358:362 cell FcγRs 353:362 cell FcγRs 353:362 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 0 82 theme IgG 51:53 arg1 fucosylation 55:66 antigen-specific IgG fucosylation 34:66 antigen-specific IgG fucosylation 34:66 Immunoassay for quantification of antigen-specific IgG fucosylation. 35752106 3 83 theme afucosylated 374:385 arg1 IgG 387:389 afucosylated IgG 374:389 afucosylated IgG 374:389 Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. 35752106 2 84 theme fucose 205:210 arg1 Absence 194:200 Absence 194:200 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain 194:271 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 2 85 theme myeloid 321:327 arg1 activation 307:316 activation 307:316 activation of myeloid and natural killer (NK) cell FcγRs 307:362 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 2 85 theme myeloid 321:327 arg1 binding 295:301 IgG binding 291:301 IgG binding 291:301 Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. 35752106 4 86 theme liquid 605:610 arg1 LC-MS 646:650 LC-MS 646:650 LC-MS 646:650 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35752106 4 86 theme liquid 605:610 arg1 spectrometry 632:643 liquid chromatography-mass spectrometry 605:643 liquid chromatography-mass spectrometry (LC-MS) 605:651 Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. 35102178 8 0 theme antiviral 1186:1194 arg1 effects 1196:1202 dose-dependent antiviral effects 1171:1202 dose-dependent antiviral effects 1171:1202 H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. 35102178 12 1 theme effectiveness 1603:1615 arg1 demonstration 1574:1586 the first demonstration 1564:1586 the first demonstration of H84T BanLec effectiveness against DNA viruses 1564:1635 This is the first demonstration of H84T BanLec effectiveness against DNA viruses. 35102178 12 1 theme effectiveness 1603:1615 arg1 This 1556:1559 This 1556:1559 This 1556:1559 This is the first demonstration of H84T BanLec effectiveness against DNA viruses. 35102178 10 2 theme overt 1328:1332 arg1 toxicity 1334:1341 no overt toxicity 1325:1341 no overt toxicity 1325:1341 Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. 35102178 8 3 from 10 µM 1123:1127 arg1 medium 1144:1149 the culture medium 1132:1149 the culture medium 1132:1149 H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. 35102178 4 4 from VZV-ORF57-Luc 661:673 arg1 mice 749:752 mice 749:752 mice 749:752 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 4 4 from VZV-ORF57-Luc 661:673 arg1 cells 718:722 cells 718:722 cells 718:722 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 4 4 from VZV-ORF57-Luc 661:673 arg1 culture 736:742 skin organ culture 725:742 skin organ culture 725:742 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 11 5 theme athymic 1389:1395 arg1 mice 1402:1405 athymic nude mice 1389:1405 athymic nude mice with human skin xenografts (NuSkin mice) 1389:1446 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 1 6 theme engineered 133:142 arg1 lectin 144:149 a molecularly engineered lectin 119:149 a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses 119:236 H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. 35102178 1 6 theme engineered 133:142 arg1 BanLec 109:114 H84T BanLec 104:114 H84T BanLec 104:114 H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. 35102178 10 7 from media 1379:1383 arg1 present 1364:1370 present 1364:1370 present 1364:1370 Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. 35102178 12 8 theme DNA 1625:1627 arg1 viruses 1629:1635 DNA viruses 1625:1635 DNA viruses 1625:1635 This is the first demonstration of H84T BanLec effectiveness against DNA viruses. 35102178 3 9 theme N-linked 585:592 arg1 glycoproteins 594:606 high-mannose N-linked glycoproteins 572:606 high-mannose N-linked glycoproteins 572:606 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 7 10 dep 14 days 1054:1060 arg1 up 1048:1049 up 1048:1049 up 1048:1049 Skin was infected and cultured up to 14 days. 35102178 11 11 theme human 1412:1416 arg1 xenografts 1423:1432 human skin xenografts 1412:1432 human skin xenografts (NuSkin mice) 1412:1446 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 11 11 theme human 1412:1416 arg1 mice 1442:1445 NuSkin mice 1435:1445 NuSkin mice 1435:1445 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 2 12 theme high-mannose 288:299 arg1 N-glycans 301:309 high-mannose N-glycans 288:309 high-mannose N-glycans 288:309 H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. 35102178 13 13 theme unexplored 1670:1679 arg1 activity 1681:1688 additional unexplored activity 1659:1688 additional unexplored activity 1659:1688 H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses. 35102178 11 14 theme virus 1537:1541 arg1 inoculation 1543:1553 intraxenograft virus inoculation 1522:1553 intraxenograft virus inoculation 1522:1553 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 10 15 theme skin 1313:1316 arg1 Histopathology 1281:1294 Histopathology 1281:1294 Histopathology of HCMV-infected skin 1281:1316 Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. 35102178 11 16 theme nude 1397:1400 arg1 mice 1402:1405 athymic nude mice 1389:1405 athymic nude mice with human skin xenografts (NuSkin mice) 1389:1446 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 12 17 theme H84T 1591:1594 arg1 effectiveness 1603:1615 H84T BanLec effectiveness 1591:1615 H84T BanLec effectiveness against DNA viruses 1591:1635 This is the first demonstration of H84T BanLec effectiveness against DNA viruses. 35102178 3 18 gly glycoproteins 594:606 arg1 glycoproteins 594:606 high-mannose N-linked glycoproteins 572:606 high-mannose N-linked glycoproteins 572:606 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 13 19 theme additional 1659:1668 arg1 activity 1681:1688 additional unexplored activity 1659:1688 additional unexplored activity 1659:1688 H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses. 35102178 0 20 from activity 41:48 arg1 skin 88:91 skin 88:91 skin 88:91 H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice. 35102178 0 20 from activity 41:48 arg1 mice 98:101 mice 98:101 mice 98:101 H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice. 35102178 0 20 from activity 41:48 arg1 cells 81:85 cells 81:85 cells 81:85 H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice. 35102178 1 21 theme broad-spectrum 176:189 arg1 activity 201:208 broad-spectrum antiviral activity 176:208 broad-spectrum antiviral activity against several RNA viruses 176:236 H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. 35102178 5 22 from HSV-1 904:908 arg1 cells 931:935 Vero cells 926:935 Vero cells 926:935 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 2 23 gly glycoproteins 263:275 arg1 glycoproteins 263:275 glycoproteins 263:275 glycoproteins containing high-mannose N-glycans 263:309 H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. 35102178 8 24 from HCMV 1090:1093 arg1 skin 1115:1118 skin 1115:1118 skin 1115:1118 H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. 35102178 11 25 theme NuSkin 1435:1440 arg1 xenografts 1423:1432 human skin xenografts 1412:1432 human skin xenografts (NuSkin mice) 1412:1446 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 11 25 theme NuSkin 1435:1440 arg1 mice 1442:1445 NuSkin mice 1435:1445 NuSkin mice 1435:1445 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 0 26 contain has 12:14 arg2 activity 41:48 broad spectrum antiviral activity 16:48 broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice 16:101 H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice. 35102178 0 26 contain has 12:14 arg1 BanLec 5:10 BanLec 5:10 BanLec 5:10 H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice. 35102178 4 27 theme organ 730:734 arg1 culture 736:742 skin organ culture 725:742 skin organ culture 725:742 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 6 28 theme reduction 967:975 arg1 mammoplasties 977:989 reduction mammoplasties 967:989 reduction mammoplasties 967:989 Human skin was obtained from reduction mammoplasties and prepared for culture. 35102178 11 29 theme intraxenograft 1522:1535 arg1 inoculation 1543:1553 intraxenograft virus inoculation 1522:1553 intraxenograft virus inoculation 1522:1553 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 5 30 from 0.23 µM 849:855 arg1 fibroblasts 829:839 human foreskin fibroblasts 814:839 human foreskin fibroblasts (HFFs) 814:846 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 5 30 from 0.23 µM 849:855 arg1 HFFs 842:845 HFFs 842:845 HFFs 842:845 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 2 31 theme virion 318:323 arg1 envelope 325:332 the virion envelope 314:332 the virion envelope 314:332 H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. 35102178 5 32 from 0.33 µM 892:898 arg1 fibroblasts 829:839 human foreskin fibroblasts 814:839 human foreskin fibroblasts (HFFs) 814:846 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 5 32 from 0.33 µM 892:898 arg1 HFFs 842:845 HFFs 842:845 HFFs 842:845 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 5 33 theme H84T 759:762 arg1 EC50 771:774 The H84T BanLec EC50 755:774 The H84T BanLec EC50 755:774 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 4 34 from R8411 709:713 arg1 mice 749:752 mice 749:752 mice 749:752 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 4 34 from R8411 709:713 arg1 cells 718:722 cells 718:722 cells 718:722 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 4 34 from R8411 709:713 arg1 culture 736:742 skin organ culture 725:742 skin organ culture 725:742 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 4 35 theme HSV-1 703:707 arg1 R8411 709:713 HSV-1 R8411 703:713 HSV-1 R8411 703:713 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 4 36 theme skin 725:728 arg1 culture 736:742 skin organ culture 725:742 skin organ culture 725:742 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 0 37 theme broad 16:20 arg1 spectrum 22:29 broad spectrum 16:29 broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice 16:101 H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice. 35102178 11 38 theme skin 1418:1421 arg1 xenografts 1423:1432 human skin xenografts 1412:1432 human skin xenografts (NuSkin mice) 1412:1446 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 11 38 theme skin 1418:1421 arg1 mice 1442:1445 NuSkin mice 1435:1445 NuSkin mice 1435:1445 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 13 39 dep other 1698:1702 arg1 glycosylated 1726:1737 glycosylated 1726:1737 glycosylated 1726:1737 H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses. 35102178 13 39 dep other 1698:1702 arg1 relevant 1716:1723 relevant 1716:1723 relevant 1716:1723 H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses. 35102178 3 40 theme herpes 526:531 arg1 virus 541:545 herpes simplex virus 1 526:547 herpes simplex virus 1 (HSV-1) 526:555 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 3 40 theme herpes 526:531 arg1 HSV-1 550:554 HSV-1 550:554 HSV-1 550:554 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 3 41 theme herpesviruses 448:460 arg1 VZV 486:488 VZV 486:488 VZV 486:488 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 3 41 theme herpesviruses 448:460 arg1 virus 479:483 human herpesviruses varicella-zoster virus 442:483 human herpesviruses varicella-zoster virus (VZV) 442:489 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 3 42 link N-linked 585:592 arg1 glycoproteins 594:606 high-mannose N-linked glycoproteins 572:606 high-mannose N-linked glycoproteins 572:606 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 2 43 contain containing 277:286 arg1 glycoproteins 263:275 glycoproteins 263:275 glycoproteins containing high-mannose N-glycans 263:309 H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. 35102178 2 43 contain containing 277:286 arg2 N-glycans 301:309 high-mannose N-glycans 288:309 high-mannose N-glycans 288:309 H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. 35102178 3 44 theme simplex 533:539 arg1 virus 541:545 herpes simplex virus 1 526:547 herpes simplex virus 1 (HSV-1) 526:555 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 3 44 theme simplex 533:539 arg1 HSV-1 550:554 HSV-1 550:554 HSV-1 550:554 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 3 45 theme varicella-zoster 462:477 arg1 VZV 486:488 VZV 486:488 VZV 486:488 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 3 45 theme varicella-zoster 462:477 arg1 virus 479:483 human herpesviruses varicella-zoster virus 442:483 human herpesviruses varicella-zoster virus (VZV) 442:489 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 0 46 theme antiviral 31:39 arg1 activity 41:48 broad spectrum antiviral activity 16:48 broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice 16:101 H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice. 35102178 8 47 theme culture 1136:1142 arg1 medium 1144:1149 the culture medium 1132:1149 the culture medium 1132:1149 H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. 35102178 8 48 theme dose-dependent 1171:1184 arg1 effects 1196:1202 dose-dependent antiviral effects 1171:1202 dose-dependent antiviral effects 1171:1202 H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. 35102178 1 49 theme antiviral 191:199 arg1 activity 201:208 broad-spectrum antiviral activity 176:208 broad-spectrum antiviral activity against several RNA viruses 176:236 H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. 35102178 0 50 theme spectrum 22:29 arg1 activity 41:48 broad spectrum antiviral activity 16:48 broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice 16:101 H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice. 35102178 5 51 theme BanLec 764:769 arg1 EC50 771:774 The H84T BanLec EC50 755:774 The H84T BanLec EC50 755:774 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 3 52 theme human 442:446 arg1 VZV 486:488 VZV 486:488 VZV 486:488 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 3 52 theme human 442:446 arg1 virus 479:483 human herpesviruses varicella-zoster virus 442:483 human herpesviruses varicella-zoster virus (VZV) 442:489 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 8 53 theme HSV-1 1099:1103 arg1 spread 1105:1110 HSV-1 spread 1099:1110 HSV-1 spread 1099:1110 H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. 35102178 11 54 with mice 1402:1405 arg1 xenografts 1423:1432 human skin xenografts 1412:1432 human skin xenografts (NuSkin mice) 1412:1446 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 11 54 with mice 1402:1405 arg1 mice 1442:1445 NuSkin mice 1435:1445 NuSkin mice 1435:1445 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 13 55 theme other 1698:1702 arg1 viruses 1739:1745 other, clinically relevant, glycosylated viruses 1698:1745 other, clinically relevant, glycosylated viruses 1698:1745 H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses. 35102178 5 56 from VZV 793:795 arg1 fibroblasts 829:839 human foreskin fibroblasts 814:839 human foreskin fibroblasts (HFFs) 814:846 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 5 56 from VZV 793:795 arg1 HFFs 842:845 HFFs 842:845 HFFs 842:845 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 9 57 theme virus 1240:1244 arg1 spread 1246:1251 virus spread 1240:1251 virus spread 1240:1251 Additionally, H84T BanLec arrested virus spread when treatment was delayed. 35102178 1 58 with bananas 163:169 arg1 activity 201:208 broad-spectrum antiviral activity 176:208 broad-spectrum antiviral activity against several RNA viruses 176:236 H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. 35102178 5 59 theme Vero 926:929 arg1 cells 931:935 Vero cells 926:935 Vero cells 926:935 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 3 60 theme human 492:496 arg1 HCMV 515:518 HCMV 515:518 HCMV 515:518 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 3 60 theme human 492:496 arg1 cytomegalovirus 498:512 human cytomegalovirus 492:512 human cytomegalovirus (HCMV) 492:519 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 4 61 theme TB40/E 676:681 arg1 HCMV-fLuc-eGFP 683:696 TB40/E HCMV-fLuc-eGFP 676:696 TB40/E HCMV-fLuc-eGFP 676:696 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 10 62 attach present 1364:1370 arg2 BanLec 1353:1358 BanLec 1353:1358 BanLec 1353:1358 Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. 35102178 10 62 attach present 1364:1370 arg1 media 1379:1383 the media 1375:1383 the media 1375:1383 Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. 35102178 10 63 theme HCMV-infected 1299:1311 arg1 skin 1313:1316 HCMV-infected skin 1299:1316 HCMV-infected skin 1299:1316 Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. 35102178 3 64 theme high-mannose 572:583 arg1 glycoproteins 594:606 high-mannose N-linked glycoproteins 572:606 high-mannose N-linked glycoproteins 572:606 It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. 35102178 8 65 from spread 1105:1110 arg1 skin 1115:1118 skin 1115:1118 skin 1115:1118 H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. 35102178 1 66 theme H84T 104:107 arg1 lectin 144:149 a molecularly engineered lectin 119:149 a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses 119:236 H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. 35102178 1 66 theme H84T 104:107 arg1 BanLec 109:114 H84T BanLec 104:114 H84T BanLec 104:114 H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. 35102178 12 67 theme first 1568:1572 arg1 demonstration 1574:1586 the first demonstration 1564:1586 the first demonstration of H84T BanLec effectiveness against DNA viruses 1564:1635 This is the first demonstration of H84T BanLec effectiveness against DNA viruses. 35102178 12 67 theme first 1568:1572 arg1 This 1556:1559 This 1556:1559 This 1556:1559 This is the first demonstration of H84T BanLec effectiveness against DNA viruses. 35102178 10 68 from present 1364:1370 arg1 media 1379:1383 the media 1375:1383 the media 1375:1383 Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. 35102178 2 69 theme BanLec 244:249 arg1 dimers 251:256 H84T BanLec dimers 239:256 H84T BanLec dimers 239:256 H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. 35102178 11 70 theme VZV 1469:1471 arg1 spread 1473:1478 VZV spread 1469:1478 VZV spread 1469:1478 In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. 35102178 4 71 from HCMV-fLuc-eGFP 683:696 arg1 mice 749:752 mice 749:752 mice 749:752 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 4 71 from HCMV-fLuc-eGFP 683:696 arg1 cells 718:722 cells 718:722 cells 718:722 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 4 71 from HCMV-fLuc-eGFP 683:696 arg1 culture 736:742 skin organ culture 725:742 skin organ culture 725:742 We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. 35102178 1 72 theme several 218:224 arg1 viruses 230:236 several RNA viruses 218:236 several RNA viruses 218:236 H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. 35102178 13 73 contain have 1654:1657 arg2 activity 1681:1688 additional unexplored activity 1659:1688 additional unexplored activity 1659:1688 H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses. 35102178 13 73 contain have 1654:1657 arg1 BanLec 1643:1648 H84T BanLec 1638:1648 H84T BanLec 1638:1648 H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses. 35102178 6 74 theme Human 938:942 arg1 skin 944:947 Human skin 938:947 Human skin 938:947 Human skin was obtained from reduction mammoplasties and prepared for culture. 35102178 5 75 theme human 814:818 arg1 fibroblasts 829:839 human foreskin fibroblasts 814:839 human foreskin fibroblasts (HFFs) 814:846 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 5 75 theme human 814:818 arg1 HFFs 842:845 HFFs 842:845 HFFs 842:845 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 5 76 from HCMV 861:864 arg1 HFFs 882:885 HFFs 882:885 HFFs 882:885 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 1 77 theme RNA 226:228 arg1 viruses 230:236 several RNA viruses 218:236 several RNA viruses 218:236 H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. 35102178 0 78 theme human 58:62 arg1 herpesviruses 64:76 human herpesviruses 58:76 human herpesviruses 58:76 H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice. 35102178 8 79 from VZV 1085:1087 arg1 skin 1115:1118 skin 1115:1118 skin 1115:1118 H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. 35102178 10 80 located present 1364:1370 arg2 BanLec 1353:1358 BanLec 1353:1358 BanLec 1353:1358 Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. 35102178 10 80 located present 1364:1370 arg1 media 1379:1383 the media 1375:1383 the media 1375:1383 Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. 35102178 5 81 theme foreskin 820:827 arg1 fibroblasts 829:839 human foreskin fibroblasts 814:839 human foreskin fibroblasts (HFFs) 814:846 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 5 81 theme foreskin 820:827 arg1 HFFs 842:845 HFFs 842:845 HFFs 842:845 The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. 35102178 12 82 theme BanLec 1596:1601 arg1 effectiveness 1603:1615 H84T BanLec effectiveness 1591:1615 H84T BanLec effectiveness against DNA viruses 1591:1635 This is the first demonstration of H84T BanLec effectiveness against DNA viruses. 35102178 13 83 theme H84T 1638:1641 arg1 BanLec 1643:1648 H84T BanLec 1638:1648 H84T BanLec 1638:1648 H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses. 36344847 2 0 with complex 359:365 arg1 antibodies 385:394 neutralizing antibodies 372:394 neutralizing antibodies 372:394 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 1 1 theme African 153:159 arg1 origin 161:166 African origin 153:166 African origin 153:166 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 1 2 theme origin 161:166 arg1 transmissions 193:205 seeded cross-species transmissions 172:205 seeded cross-species transmissions of HIV-1 and HIV-2 172:224 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 1 2 theme origin 161:166 arg1 primates 141:148 non-human primates 131:148 non-human primates of African origin 131:166 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 5 3 dep in 840:841 arg1 situ 843:846 situ 843:846 situ 843:846 We also investigated in situ SIVmac-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. 36344847 2 4 theme envelope 300:307 arg1 trimers 315:321 soluble envelope (Env) trimers 292:321 soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) 292:354 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 5 5 theme antibody-bound 962:975 arg1 complex 977:983 an antibody-bound complex 959:983 an antibody-bound complex 959:983 We also investigated in situ SIVmac-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. 36344847 4 6 theme variable 590:597 arg1 loops 599:603 The defined variable loops 578:603 The defined variable loops 578:603 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 3 7 theme Env 566:568 arg1 trimer 570:575 the Env trimer 562:575 the Env trimer 562:575 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 2 8 theme soluble 292:298 arg1 trimers 315:321 soluble envelope (Env) trimers 292:321 soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) 292:354 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 2 9 from SIV 343:345 arg1 stabilization 252:264 prefusion stabilization 242:264 prefusion stabilization 242:264 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 2 9 from SIV 343:345 arg1 structures 278:287 cryo-EM structures 270:287 cryo-EM structures 270:287 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 2 9 from SIV 343:345 arg1 trimers 315:321 soluble envelope (Env) trimers 292:321 soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) 292:354 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 1 10 theme immunodeficiency 60:75 arg1 viruses 77:83 Simian immunodeficiency viruses 53:83 Simian immunodeficiency viruses (SIVs) 53:90 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 1 10 theme immunodeficiency 60:75 arg1 SIVs 86:89 SIVs 86:89 SIVs 86:89 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 1 10 theme immunodeficiency 60:75 arg1 lentiviruses 96:107 lentiviruses 96:107 lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2 96:224 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 4 11 theme defined 582:588 arg1 loops 599:603 The defined variable loops 578:603 The defined variable loops 578:603 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 5 12 theme SIVmac-Env 848:857 arg1 trimers 859:865 in situ SIVmac-Env trimers 840:865 in situ SIVmac-Env trimers 840:865 We also investigated in situ SIVmac-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. 36344847 3 13 theme residue-level 422:434 arg1 definition 436:445 residue-level definition 422:445 residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer 422:575 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 6 14 theme immune 1164:1169 arg1 evasion 1171:1177 immune evasion 1164:1177 immune evasion conserved throughout SIV evolution 1164:1212 Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution. 36344847 4 15 theme V1 759:760 arg1 inserts 762:768 V1 inserts 759:768 V1 inserts 759:768 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 6 16 theme variable-loop 1115:1127 arg1 mechanisms 1150:1159 variable-loop and glycan-shielding mechanisms 1115:1159 variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution 1115:1212 Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution. 36344847 1 17 theme seeded 172:177 arg1 transmissions 193:205 seeded cross-species transmissions 172:205 seeded cross-species transmissions of HIV-1 and HIV-2 172:224 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 2 18 theme trimers 315:321 arg1 stabilization 252:264 prefusion stabilization 242:264 prefusion stabilization 242:264 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 2 18 theme trimers 315:321 arg1 structures 278:287 cryo-EM structures 270:287 cryo-EM structures 270:287 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 6 19 theme trimer 1094:1099 arg1 structure 1069:1077 the prefusion-closed structure 1048:1077 the prefusion-closed structure of the SIV-Env trimer 1048:1099 Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution. 36344847 1 20 theme cross-species 179:191 arg1 transmissions 193:205 seeded cross-species transmissions 172:205 seeded cross-species transmissions of HIV-1 and HIV-2 172:224 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 0 21 theme Cryo-EM 0:6 arg1 structures 8:17 Cryo-EM structures 0:17 Cryo-EM structures of prefusion SIV envelope trimer 0:50 Cryo-EM structures of prefusion SIV envelope trimer. 36344847 3 22 theme trimer 570:575 arg1 coverage 550:557 variable-loop coverage 536:557 variable-loop coverage of the Env trimer 536:575 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 2 23 from stabilization 252:264 arg1 SIVmac 348:353 SIVmac 348:353 SIVmac 348:353 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 2 23 from stabilization 252:264 arg1 complex 359:365 complex 359:365 complex with neutralizing antibodies 359:394 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 2 23 from stabilization 252:264 arg1 SIV 343:345 rhesus macaque SIV 328:345 rhesus macaque SIV (SIVmac) 328:354 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 6 24 theme SIV-Env 1086:1092 arg1 trimer 1094:1099 the SIV-Env trimer 1082:1099 the SIV-Env trimer 1082:1099 Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution. 36344847 0 25 theme prefusion 22:30 arg1 trimer 45:50 prefusion SIV envelope trimer 22:50 prefusion SIV envelope trimer 22:50 Cryo-EM structures of prefusion SIV envelope trimer. 36344847 3 26 dep loops 490:494 arg1 V2 504:505 V2 504:505 V2 504:505 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 3 26 dep loops 490:494 arg1 V1 497:498 V1 497:498 V1 497:498 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 3 26 dep loops 490:494 arg1 loops 490:494 SIV-specific disulfide-bonded variable loops 451:494 SIV-specific disulfide-bonded variable loops (V1 and V2) 451:506 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 5 27 theme subnanometer 930:941 arg1 resolutions 943:953 subnanometer resolutions 930:953 subnanometer resolutions for an antibody-bound complex and a ligand-free state 930:1007 We also investigated in situ SIVmac-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. 36344847 2 28 theme Env 310:312 arg1 trimers 315:321 soluble envelope (Env) trimers 292:321 soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) 292:354 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 4 29 theme lectin 803:808 arg1 jacalin 810:816 the O-link-specific lectin jacalin 783:816 the O-link-specific lectin jacalin 783:816 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 4 30 theme assembled 631:639 arg1 shields 652:658 assembled Env-glycan shields 631:658 assembled Env-glycan shields 631:658 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 5 31 theme cryo-electron 891:903 arg1 structures 916:925 cryo-electron tomography structures 891:925 cryo-electron tomography structures 891:925 We also investigated in situ SIVmac-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. 36344847 1 32 theme HIV-1 210:214 arg1 transmissions 193:205 seeded cross-species transmissions 172:205 seeded cross-species transmissions of HIV-1 and HIV-2 172:224 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 1 32 theme HIV-1 210:214 arg1 primates 141:148 non-human primates 131:148 non-human primates of African origin 131:166 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 0 33 theme envelope 36:43 arg1 trimer 45:50 prefusion SIV envelope trimer 22:50 prefusion SIV envelope trimer 22:50 Cryo-EM structures of prefusion SIV envelope trimer. 36344847 6 34 theme evasion 1171:1177 arg1 mechanisms 1150:1159 variable-loop and glycan-shielding mechanisms 1115:1159 variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution 1115:1212 Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution. 36344847 4 35 theme Env-glycan 641:650 arg1 shields 652:658 assembled Env-glycan shields 631:658 assembled Env-glycan shields 631:658 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 3 36 theme disulfide-bonded 464:479 arg1 V2 504:505 V2 504:505 V2 504:505 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 3 36 theme disulfide-bonded 464:479 arg1 V1 497:498 V1 497:498 V1 497:498 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 3 36 theme disulfide-bonded 464:479 arg1 loops 490:494 SIV-specific disulfide-bonded variable loops 451:494 SIV-specific disulfide-bonded variable loops (V1 and V2) 451:506 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 0 37 theme SIV 32:34 arg1 trimer 45:50 prefusion SIV envelope trimer 22:50 prefusion SIV envelope trimer 22:50 Cryo-EM structures of prefusion SIV envelope trimer. 36344847 4 38 theme O-link-specific 787:801 arg1 jacalin 810:816 the O-link-specific lectin jacalin 783:816 the O-link-specific lectin jacalin 783:816 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 5 39 theme in 840:841 arg1 trimers 859:865 in situ SIVmac-Env trimers 840:865 in situ SIVmac-Env trimers 840:865 We also investigated in situ SIVmac-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. 36344847 1 40 theme HIV-2 220:224 arg1 transmissions 193:205 seeded cross-species transmissions 172:205 seeded cross-species transmissions of HIV-1 and HIV-2 172:224 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 1 40 theme HIV-2 220:224 arg1 primates 141:148 non-human primates 131:148 non-human primates of African origin 131:166 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 6 41 theme prefusion-closed 1052:1067 arg1 structure 1069:1077 the prefusion-closed structure 1048:1077 the prefusion-closed structure of the SIV-Env trimer 1048:1099 Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution. 36344847 5 42 theme tomography 905:914 arg1 structures 916:925 cryo-electron tomography structures 891:925 cryo-electron tomography structures 891:925 We also investigated in situ SIVmac-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. 36344847 0 43 theme trimer 45:50 arg1 structures 8:17 Cryo-EM structures 0:17 Cryo-EM structures of prefusion SIV envelope trimer 0:50 Cryo-EM structures of prefusion SIV envelope trimer. 36344847 6 44 theme SIV 1200:1202 arg1 evolution 1204:1212 SIV evolution 1200:1212 SIV evolution 1200:1212 Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution. 36344847 2 45 theme macaque 335:341 arg1 SIVmac 348:353 SIVmac 348:353 SIVmac 348:353 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 2 45 theme macaque 335:341 arg1 SIV 343:345 rhesus macaque SIV 328:345 rhesus macaque SIV (SIVmac) 328:354 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 4 46 link O-linked 715:722 arg1 glycans 724:730 O-linked glycans 715:730 O-linked glycans 715:730 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 4 46 link O-linked 715:722 arg1 latter 737:742 latter 737:742 latter 737:742 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 2 47 theme cryo-EM 270:276 arg1 structures 278:287 cryo-EM structures 270:287 cryo-EM structures 270:287 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 4 48 theme O-linked 715:722 arg1 glycans 724:730 O-linked glycans 715:730 O-linked glycans 715:730 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 4 48 theme O-linked 715:722 arg1 latter 737:742 latter 737:742 latter 737:742 The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. 36344847 2 49 from structures 278:287 arg1 SIVmac 348:353 SIVmac 348:353 SIVmac 348:353 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 2 49 from structures 278:287 arg1 complex 359:365 complex 359:365 complex with neutralizing antibodies 359:394 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 2 49 from structures 278:287 arg1 SIV 343:345 rhesus macaque SIV 328:345 rhesus macaque SIV (SIVmac) 328:354 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 5 50 theme ligand-free 991:1001 arg1 state 1003:1007 a ligand-free state 989:1007 a ligand-free state 989:1007 We also investigated in situ SIVmac-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. 36344847 1 51 theme Simian 53:58 arg1 viruses 77:83 Simian immunodeficiency viruses 53:83 Simian immunodeficiency viruses (SIVs) 53:90 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 1 51 theme Simian 53:58 arg1 SIVs 86:89 SIVs 86:89 SIVs 86:89 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 1 51 theme Simian 53:58 arg1 lentiviruses 96:107 lentiviruses 96:107 lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2 96:224 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 1 52 theme non-human 131:139 arg1 primates 141:148 non-human primates 131:148 non-human primates of African origin 131:166 Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. 36344847 3 53 theme SIV-specific 451:462 arg1 V2 504:505 V2 504:505 V2 504:505 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 3 53 theme SIV-specific 451:462 arg1 V1 497:498 V1 497:498 V1 497:498 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 3 53 theme SIV-specific 451:462 arg1 loops 490:494 SIV-specific disulfide-bonded variable loops 451:494 SIV-specific disulfide-bonded variable loops (V1 and V2) 451:506 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 3 54 theme variable 481:488 arg1 V2 504:505 V2 504:505 V2 504:505 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 3 54 theme variable 481:488 arg1 V1 497:498 V1 497:498 V1 497:498 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 3 54 theme variable 481:488 arg1 loops 490:494 SIV-specific disulfide-bonded variable loops 451:494 SIV-specific disulfide-bonded variable loops (V1 and V2) 451:506 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 3 55 used used 518:521 arg2 we 515:516 we 515:516 we 515:516 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 2 56 theme neutralizing 372:383 arg1 antibodies 385:394 neutralizing antibodies 372:394 neutralizing antibodies 372:394 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 3 57 theme variable-loop 536:548 arg1 coverage 550:557 variable-loop coverage 536:557 variable-loop coverage of the Env trimer 536:575 These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. 36344847 2 58 theme prefusion 242:250 arg1 stabilization 252:264 prefusion stabilization 242:264 prefusion stabilization 242:264 Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. 36344847 6 59 theme glycan-shielding 1133:1148 arg1 mechanisms 1150:1159 variable-loop and glycan-shielding mechanisms 1115:1159 variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution 1115:1212 Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution. 37398215 6 0 theme responsive 1072:1081 arg1 mutations 1083:1091 responsive mutations 1072:1091 responsive mutations in genes encoding secreted glycoproteins 1072:1132 Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. 37398215 11 1 theme associated 1696:1705 arg1 GDLD 1707:1710 Trop-2-Q118E associated GDLD 1683:1710 Trop-2-Q118E associated GDLD 1683:1710 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 1 2 gly glycoproteins 167:179 arg1 glycoproteins 167:179 mis-folded glycoproteins 156:179 mis-folded glycoproteins 156:179 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 3 3 theme ER 530:531 arg1 retention 533:541 UGGT-mediated ER retention 516:541 UGGT-mediated ER retention 516:541 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 1 4 theme glycoprotein 272:283 arg1 checkpoint 248:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 1 4 theme glycoprotein 272:283 arg1 UGGT 307:310 UGGT 307:310 UGGT 307:310 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 1 4 theme glycoprotein 272:283 arg1 glucosyl-transferase 285:304 UDP-glucose glycoprotein glucosyl-transferase 260:304 UDP-glucose glycoprotein glucosyl-transferase (UGGT) 260:311 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 14 5 theme disease 2262:2268 arg1 mutant 2270:2275 The Trop-2-Q118E glycoprotein disease mutant 2232:2275 The Trop-2-Q118E glycoprotein disease mutant 2232:2275 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 3 6 theme UGGT-mediated 516:528 arg1 retention 533:541 UGGT-mediated ER retention 516:541 UGGT-mediated ER retention 516:541 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 13 7 theme double 2208:2213 arg1 cells 2225:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 4 8 theme variant 715:721 arg1 localisation 676:687 the subcellular localisation 660:687 the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous drop- like corneal dystrophy (GDLD) 660:782 Here, we investigated the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous drop- like corneal dystrophy (GDLD). 37398215 8 9 theme limiting 1238:1245 arg1 case 1247:1250 a limiting case 1236:1250 a limiting case of UGGT inhibition 1236:1269 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 8 9 theme limiting 1238:1245 arg1 cells 1282:1286 mammalian cells 1272:1286 mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions 1272:1372 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 14 10 theme Trop-2-Q118E 2236:2247 arg1 mutant 2270:2275 The Trop-2-Q118E glycoprotein disease mutant 2232:2275 The Trop-2-Q118E glycoprotein disease mutant 2232:2275 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 9 11 theme mutant 1436:1441 arg1 localisation 1398:1409 The membrane localisation 1385:1409 The membrane localisation of the Trop-2-Q118E-EYFP mutant 1385:1441 The membrane localisation of the Trop-2-Q118E-EYFP mutant was successfully rescued in UGGT1 and UGGT1/2 cells. 37398215 3 12 theme rare 553:556 arg1 disease 558:564 rare disease 553:564 rare disease 553:564 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 12 13 theme human 2031:2035 arg1 mutant 2063:2068 the human Trop-2-Q118E glycoprotein mutant 2027:2068 the human Trop-2-Q118E glycoprotein mutant 2027:2068 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 3 14 from gene 510:513 arg1 background 447:456 the background 443:456 the background of a congenital mutation in a secreted glycoprotein gene 443:513 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 9 15 theme UGGT1/2 1481:1487 arg1 cells 1489:1493 UGGT1/2 cells 1481:1493 UGGT1/2 cells 1481:1493 The membrane localisation of the Trop-2-Q118E-EYFP mutant was successfully rescued in UGGT1 and UGGT1/2 cells. 37398215 12 16 theme glycoprotein 2050:2061 arg1 mutant 2063:2068 the human Trop-2-Q118E glycoprotein mutant 2027:2068 the human Trop-2-Q118E glycoprotein mutant 2027:2068 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 8 17 theme inhibition 1260:1269 arg1 case 1247:1250 a limiting case 1236:1250 a limiting case of UGGT inhibition 1236:1269 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 8 17 theme inhibition 1260:1269 arg1 cells 1282:1286 mammalian cells 1272:1286 mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions 1272:1372 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 13 18 from pathway 2111:2117 arg1 cells 2132:2136 wild type cells 2122:2136 wild type cells 2122:2136 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 1 19 theme ER- 200:202 arg1 checkpoint 248:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 1 19 theme ER- 200:202 arg1 glucosyl-transferase 285:304 UDP-glucose glycoprotein glucosyl-transferase 260:304 UDP-glucose glycoprotein glucosyl-transferase (UGGT) 260:311 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 8 20 theme mammalian 1272:1280 arg1 case 1247:1250 a limiting case 1236:1250 a limiting case of UGGT inhibition 1236:1269 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 8 20 theme mammalian 1272:1280 arg1 cells 1282:1286 mammalian cells 1272:1286 mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions 1272:1372 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 11 21 theme secreted 1890:1897 arg1 mutants 1912:1918 responsive secreted glycoprotein mutants 1879:1918 responsive secreted glycoprotein mutants 1879:1918 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 13 22 theme UGGT1 2179:2183 arg1 cells 2225:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 1 23 theme eukaryotic 214:223 arg1 checkpoint 248:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 1 23 theme eukaryotic 214:223 arg1 glucosyl-transferase 285:304 UDP-glucose glycoprotein glucosyl-transferase 260:304 UDP-glucose glycoprotein glucosyl-transferase (UGGT) 260:311 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 3 24 gly glycoprotein 585:596 arg1 glycoprotein 585:596 the mutant glycoprotein 574:596 the mutant glycoprotein 574:596 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 1 25 theme reticulum 128:136 arg1 retention 143:151 Endoplasmic reticulum (ER) retention 116:151 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins 116:179 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 14 26 theme UGGT1 2375:2379 arg1 substrate 2381:2389 a bona fide cellular UGGT1 substrate 2354:2389 a bona fide cellular UGGT1 substrate 2354:2389 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 14 26 theme UGGT1 2375:2379 arg1 it 2348:2349 it 2348:2349 it 2348:2349 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 0 27 theme mutant 60:65 arg1 glycoprotein 67:78 mis-folded mutant glycoprotein 49:78 mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells 49:113 Rescue of secretion of a rare-disease associated mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells. 37398215 13 28 theme type 2127:2130 arg1 cells 2132:2136 wild type cells 2122:2136 wild type cells 2122:2136 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 3 29 theme mutant 628:633 arg1 " 634:634 "responsive mutant" 616:634 "responsive mutant" 616:634 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 3 29 theme mutant 628:633 arg1 activity 606:613 activity 606:613 activity ("responsive mutant") 606:635 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 12 30 theme mutant 2063:2068 arg1 EYFP-fusion 2012:2022 an EYFP-fusion 2009:2022 an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant 2009:2068 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 8 31 theme UGGT1 1338:1342 arg1 inhibition 1320:1329 CRISPR/Cas9-mediated inhibition 1299:1329 CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions 1299:1372 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 4 32 theme Trop-2 702:707 arg1 variant 715:721 the human Trop-2 Q118E variant 692:721 the human Trop-2 Q118E variant 692:721 Here, we investigated the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous drop- like corneal dystrophy (GDLD). 37398215 11 33 theme of-secretion 1833:1844 arg1 testing 1735:1741 the testing 1731:1741 the testing of modulators of ER glycoprotein folding Quality Control (ERQC) 1731:1805 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 33 theme of-secretion 1833:1844 arg1 drugs 1846:1850 broad-spectrum rescue- of-secretion drugs 1810:1850 broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants 1810:1918 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 12 34 theme 293T 1977:1980 arg1 cells 1982:1986 HEK 293T cells 1973:1986 HEK 293T cells 1973:1986 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 1 35 theme mis-folded 156:165 arg1 glycoproteins 167:179 mis-folded glycoproteins 156:179 mis-folded glycoproteins 156:179 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 8 36 theme gene 1357:1360 arg1 expressions 1362:1372 UGGT2 gene expressions 1351:1372 UGGT2 gene expressions 1351:1372 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 11 37 theme broad-spectrum 1810:1823 arg1 testing 1735:1741 the testing 1731:1741 the testing of modulators of ER glycoprotein folding Quality Control (ERQC) 1731:1805 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 37 theme broad-spectrum 1810:1823 arg1 drugs 1846:1850 broad-spectrum rescue- of-secretion drugs 1810:1850 broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants 1810:1918 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 0 38 theme knock-out 89:97 arg1 cells 109:113 UGGT1 knock-out mammalian cells 83:113 UGGT1 knock-out mammalian cells 83:113 Rescue of secretion of a rare-disease associated mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells. 37398215 13 39 theme secretory 2101:2109 arg1 pathway 2111:2117 the secretory pathway 2097:2117 the secretory pathway in wild type cells 2097:2136 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 0 40 gly glycoprotein 67:78 arg1 glycoprotein 67:78 mis-folded mutant glycoprotein 49:78 mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells 49:113 Rescue of secretion of a rare-disease associated mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells. 37398215 8 41 theme CRISPR/Cas9-mediated 1299:1318 arg1 inhibition 1320:1329 CRISPR/Cas9-mediated inhibition 1299:1329 CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions 1299:1372 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 12 42 theme UGGT1/2 1956:1962 arg1 genes 1964:1968 the UGGT1 and UGGT1/2 genes 1942:1968 genes 1964:1968 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 1 43 gly glycoprotein 272:283 arg1 glycoprotein 272:283 UDP-glucose glycoprotein glucosyl-transferase 260:304 UDP-glucose glycoprotein glucosyl-transferase (UGGT) 260:311 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 14 44 theme glycoprotein 2249:2260 arg1 mutant 2270:2275 The Trop-2-Q118E glycoprotein disease mutant 2232:2275 The Trop-2-Q118E glycoprotein disease mutant 2232:2275 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 4 45 theme gelatinous 737:746 arg1 drop- 748:752 gelatinous drop- 737:752 gelatinous drop- 737:752 Here, we investigated the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous drop- like corneal dystrophy (GDLD). 37398215 5 46 theme wild 803:806 arg1 Trop-2 813:818 the wild type Trop-2 799:818 the wild type Trop-2 799:818 Compared with the wild type Trop-2, which is correctly localised at the plasma membrane, the Trop-2-Q118E variant is found to be heavily retained in the ER. 37398215 6 47 theme congenital 1038:1047 arg1 disease 1054:1060 congenital rare disease 1038:1060 congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins 1038:1132 Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. 37398215 3 48 gly glycoprotein 497:508 arg1 glycoprotein 497:508 a secreted glycoprotein gene 486:513 a secreted glycoprotein gene 486:513 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 14 49 theme human 2317:2321 arg1 cells 2323:2327 human cells 2317:2327 human cells demonstrating that it is a bona fide cellular UGGT1 substrate 2317:2389 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 0 50 theme secretion 10:18 arg1 Rescue 0:5 Rescue 0:5 Rescue of secretion of a rare-disease 0:36 Rescue of secretion of a rare-disease associated mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells. 37398215 13 51 theme single 2189:2194 arg1 cells 2225:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 3 52 theme congenital 463:472 arg1 mutation 474:481 a congenital mutation 461:481 a congenital mutation in a secreted glycoprotein gene 461:513 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 11 53 gly glycoprotein 1899:1910 arg1 glycoprotein 1899:1910 responsive secreted glycoprotein mutants 1879:1918 responsive secreted glycoprotein mutants 1879:1918 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 8 54 used used 1379:1382 arg2 cells 1282:1286 mammalian cells 1272:1286 mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions 1272:1372 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 8 54 used used 1379:1382 arg2 case 1247:1250 a limiting case 1236:1250 a limiting case of UGGT inhibition 1236:1269 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 12 55 theme UGGT1 1946:1950 arg1 genes 1964:1968 the UGGT1 and UGGT1/2 genes 1942:1968 genes 1964:1968 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 6 56 theme rescue-of-secretion 993:1011 arg1 strategy 1025:1032 a rescue-of-secretion therapeutic strategy 991:1032 a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins 991:1132 Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. 37398215 6 56 theme rescue-of-secretion 993:1011 arg1 modulation 977:986 UGGT modulation 972:986 UGGT modulation 972:986 Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. 37398215 11 57 theme modulators 1746:1755 arg1 drugs 1846:1850 broad-spectrum rescue- of-secretion drugs 1810:1850 broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants 1810:1918 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 57 theme modulators 1746:1755 arg1 testing 1735:1741 the testing 1731:1741 the testing of modulators of ER glycoprotein folding Quality Control (ERQC) 1731:1805 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 3 58 from mutation 474:481 arg1 gene 510:513 a secreted glycoprotein gene 486:513 a secreted glycoprotein gene 486:513 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 6 59 theme secreted 1111:1118 arg1 glycoproteins 1120:1132 secreted glycoproteins 1111:1132 secreted glycoproteins 1111:1132 Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. 37398215 14 60 dep bona 2356:2359 arg1 fide 2361:2364 fide 2361:2364 fide 2361:2364 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 2 61 gly glycoprotein 349:360 arg1 glycoprotein 349:360 a mis-folded glycoprotein 336:360 a mis-folded glycoprotein 336:360 The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. 37398215 2 62 link N-linked 422:429 arg1 glycans 431:437 its N-linked glycans 418:437 its N-linked glycans 418:437 The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. 37398215 3 63 theme secreted 488:495 arg1 gene 510:513 a secreted glycoprotein gene 486:513 a secreted glycoprotein gene 486:513 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 1 64 theme glycoprotein 225:236 arg1 checkpoint 248:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 1 64 theme glycoprotein 225:236 arg1 glucosyl-transferase 285:304 UDP-glucose glycoprotein glucosyl-transferase 260:304 UDP-glucose glycoprotein glucosyl-transferase (UGGT) 260:311 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 12 65 theme Synopsis 1921:1928 arg1 Deletion 1930:1937 Synopsis Deletion 1921:1937 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells 1921:1986 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 14 66 gly glycoprotein 2249:2260 arg1 glycoprotein 2249:2260 The Trop-2-Q118E glycoprotein disease mutant 2232:2275 The Trop-2-Q118E glycoprotein disease mutant 2232:2275 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 2 67 theme N-linked 422:429 arg1 glycans 431:437 its N-linked glycans 418:437 its N-linked glycans 418:437 The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. 37398215 11 68 theme Trop-2-Q118E 1683:1694 arg1 GDLD 1707:1710 Trop-2-Q118E associated GDLD 1683:1710 Trop-2-Q118E associated GDLD 1683:1710 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 7 69 theme scanning 1212:1219 arg1 microscopy 1221:1230 confocal laser scanning microscopy 1197:1230 confocal laser scanning microscopy 1197:1230 We investigated secretion of a EYFP-fusion of Trop-2-Q118E by confocal laser scanning microscopy. 37398215 6 70 from mutations 1083:1091 arg1 genes 1096:1100 genes 1096:1100 genes encoding secreted glycoproteins 1096:1132 Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. 37398215 2 71 theme ER 379:380 arg1 retention 382:390 ER retention 379:390 ER retention 379:390 The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. 37398215 1 72 theme UDP-glucose 260:270 arg1 checkpoint 248:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 1 72 theme UDP-glucose 260:270 arg1 UGGT 307:310 UGGT 307:310 UGGT 307:310 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 1 72 theme UDP-glucose 260:270 arg1 glucosyl-transferase 285:304 UDP-glucose glycoprotein glucosyl-transferase 260:304 UDP-glucose glycoprotein glucosyl-transferase (UGGT) 260:311 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 11 73 theme GDLD 1707:1710 arg1 treatment 1670:1678 the treatment 1666:1678 the treatment of Trop-2-Q118E associated GDLD 1666:1710 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 3 74 theme mutant 578:583 arg1 glycoprotein 585:596 the mutant glycoprotein 574:596 the mutant glycoprotein 574:596 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 11 75 dep novel 1635:1639 arg1 therapeutic 1641:1651 therapeutic 1641:1651 therapeutic 1641:1651 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 13 76 from membrane 2167:2174 arg1 cells 2225:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 12 77 gly glycoprotein 2050:2061 arg1 glycoprotein 2050:2061 the human Trop-2-Q118E glycoprotein mutant 2027:2068 the human Trop-2-Q118E glycoprotein mutant 2027:2068 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 1 78 theme glycoproteins 167:179 arg1 retention 143:151 Endoplasmic reticulum (ER) retention 116:151 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins 116:179 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 2 79 theme mis-folded 338:347 arg1 glycoprotein 349:360 a mis-folded glycoprotein 336:360 a mis-folded glycoprotein 336:360 The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. 37398215 4 80 theme subcellular 664:674 arg1 localisation 676:687 the subcellular localisation 660:687 the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous drop- like corneal dystrophy (GDLD) 660:782 Here, we investigated the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous drop- like corneal dystrophy (GDLD). 37398215 11 81 theme UGGT1 1604:1608 arg1 modulation 1610:1619 UGGT1 modulation 1604:1619 UGGT1 modulation 1604:1619 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 12 82 theme Trop-2-Q118E 2037:2048 arg1 mutant 2063:2068 the human Trop-2-Q118E glycoprotein mutant 2027:2068 the human Trop-2-Q118E glycoprotein mutant 2027:2068 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 5 83 theme Trop-2-Q118E 878:889 arg1 variant 891:897 the Trop-2-Q118E variant 874:897 the Trop-2-Q118E variant 874:897 Compared with the wild type Trop-2, which is correctly localised at the plasma membrane, the Trop-2-Q118E variant is found to be heavily retained in the ER. 37398215 8 84 theme UGGT 1255:1258 arg1 inhibition 1260:1269 UGGT inhibition 1255:1269 UGGT inhibition 1255:1269 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 11 85 theme rare 1855:1858 arg1 diseases 1860:1867 rare diseases 1855:1867 rare diseases caused by responsive secreted glycoprotein mutants 1855:1918 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 5 86 theme plasma 857:862 arg1 membrane 864:871 the plasma membrane 853:871 the plasma membrane 853:871 Compared with the wild type Trop-2, which is correctly localised at the plasma membrane, the Trop-2-Q118E variant is found to be heavily retained in the ER. 37398215 1 87 theme localised 204:212 arg1 checkpoint 248:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 1 87 theme localised 204:212 arg1 glucosyl-transferase 285:304 UDP-glucose glycoprotein glucosyl-transferase 260:304 UDP-glucose glycoprotein glucosyl-transferase (UGGT) 260:311 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 12 88 from Deletion 1930:1937 arg1 cells 1982:1986 HEK 293T cells 1973:1986 HEK 293T cells 1973:1986 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 11 89 from drugs 1846:1850 arg1 diseases 1860:1867 rare diseases 1855:1867 rare diseases caused by responsive secreted glycoprotein mutants 1855:1918 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 0 90 from glycoprotein 67:78 arg1 cells 109:113 UGGT1 knock-out mammalian cells 83:113 UGGT1 knock-out mammalian cells 83:113 Rescue of secretion of a rare-disease associated mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells. 37398215 7 91 theme confocal 1197:1204 arg1 microscopy 1221:1230 confocal laser scanning microscopy 1197:1230 confocal laser scanning microscopy 1197:1230 We investigated secretion of a EYFP-fusion of Trop-2-Q118E by confocal laser scanning microscopy. 37398215 13 92 theme -/- 2185:2187 arg1 cells 2225:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 1 93 theme Endoplasmic 116:126 arg1 ER 139:140 ER 139:140 ER 139:140 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 1 93 theme Endoplasmic 116:126 arg1 reticulum 128:136 Endoplasmic reticulum 116:136 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins 116:179 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 12 94 theme EYFP-fusion 2012:2022 arg1 secretion 1996:2004 secretion 1996:2004 secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant 1996:2068 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 11 95 theme Control 1792:1798 arg1 modulators 1746:1755 modulators 1746:1755 modulators of ER glycoprotein folding Quality Control (ERQC) 1746:1805 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 4 96 theme Q118E 709:713 arg1 variant 715:721 the human Trop-2 Q118E variant 692:721 the human Trop-2 Q118E variant 692:721 Here, we investigated the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous drop- like corneal dystrophy (GDLD). 37398215 11 97 theme responsive 1879:1888 arg1 mutants 1912:1918 responsive secreted glycoprotein mutants 1879:1918 responsive secreted glycoprotein mutants 1879:1918 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 98 gly glycoprotein 1763:1774 arg1 glycoprotein 1763:1774 ER glycoprotein folding Quality Control 1760:1798 ER glycoprotein folding Quality Control (ERQC) 1760:1805 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 13 99 theme cell 2162:2165 arg1 membrane 2167:2174 the cell membrane 2158:2174 the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells 2158:2229 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 3 100 theme responsive 617:626 arg1 " 634:634 "responsive mutant" 616:634 "responsive mutant" 616:634 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 3 100 theme responsive 617:626 arg1 activity 606:613 activity 606:613 activity ("responsive mutant") 606:635 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 13 101 theme knock-out 2215:2223 arg1 cells 2225:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 UGGT1 -/- single and UGGT1/2 double knock-out cells 2179:2229 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 14 102 theme cellular 2366:2373 arg1 substrate 2381:2389 a bona fide cellular UGGT1 substrate 2354:2389 a bona fide cellular UGGT1 substrate 2354:2389 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 14 102 theme cellular 2366:2373 arg1 it 2348:2349 it 2348:2349 it 2348:2349 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 7 103 theme laser 1206:1210 arg1 microscopy 1221:1230 confocal laser scanning microscopy 1197:1230 confocal laser scanning microscopy 1197:1230 We investigated secretion of a EYFP-fusion of Trop-2-Q118E by confocal laser scanning microscopy. 37398215 0 104 theme UGGT1 83:87 arg1 cells 109:113 UGGT1 knock-out mammalian cells 83:113 UGGT1 knock-out mammalian cells 83:113 Rescue of secretion of a rare-disease associated mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells. 37398215 4 105 theme human 696:700 arg1 variant 715:721 the human Trop-2 Q118E variant 692:721 the human Trop-2 Q118E variant 692:721 Here, we investigated the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous drop- like corneal dystrophy (GDLD). 37398215 14 106 theme bona 2356:2359 arg1 substrate 2381:2389 a bona fide cellular UGGT1 substrate 2354:2389 a bona fide cellular UGGT1 substrate 2354:2389 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 14 106 theme bona 2356:2359 arg1 it 2348:2349 it 2348:2349 it 2348:2349 The Trop-2-Q118E glycoprotein disease mutant is efficiently glucosylated by UGGT1 in human cells demonstrating that it is a bona fide cellular UGGT1 substrate. 37398215 0 107 theme mammalian 99:107 arg1 cells 109:113 UGGT1 knock-out mammalian cells 83:113 UGGT1 knock-out mammalian cells 83:113 Rescue of secretion of a rare-disease associated mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells. 37398215 1 108 gly glycoprotein 225:236 arg1 glycoprotein 225:236 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 8 109 theme UGGT2 1351:1355 arg1 expressions 1362:1372 UGGT2 gene expressions 1351:1372 UGGT2 gene expressions 1351:1372 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 4 110 theme corneal 759:765 arg1 dystrophy 767:775 corneal dystrophy 759:775 corneal dystrophy (GDLD) 759:782 Here, we investigated the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous drop- like corneal dystrophy (GDLD). 37398215 4 110 theme corneal 759:765 arg1 GDLD 778:781 GDLD 778:781 GDLD 778:781 Here, we investigated the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous drop- like corneal dystrophy (GDLD). 37398215 11 111 theme rescue- 1825:1831 arg1 testing 1735:1741 the testing 1731:1741 the testing of modulators of ER glycoprotein folding Quality Control (ERQC) 1731:1805 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 111 theme rescue- 1825:1831 arg1 drugs 1846:1850 broad-spectrum rescue- of-secretion drugs 1810:1850 broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants 1810:1918 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 7 112 theme Trop-2-Q118E 1181:1192 arg1 EYFP-fusion 1166:1176 a EYFP-fusion 1164:1176 a EYFP-fusion of Trop-2-Q118E 1164:1192 We investigated secretion of a EYFP-fusion of Trop-2-Q118E by confocal laser scanning microscopy. 37398215 12 113 theme genes 1964:1968 arg1 Deletion 1930:1937 Synopsis Deletion 1921:1937 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells 1921:1986 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 2 114 theme glycans 431:437 arg1 glycans 431:437 its N-linked glycans 418:437 its N-linked glycans 418:437 The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. 37398215 2 114 theme glycans 431:437 arg1 one 411:413 one 411:413 one 411:413 The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. 37398215 6 115 gly glycoproteins 1120:1132 arg1 glycoproteins 1120:1132 secreted glycoproteins 1111:1132 secreted glycoproteins 1111:1132 Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. 37398215 8 116 theme expressions 1362:1372 arg1 inhibition 1320:1329 CRISPR/Cas9-mediated inhibition 1299:1329 CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions 1299:1372 As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. 37398215 7 117 theme EYFP-fusion 1166:1176 arg1 secretion 1151:1159 secretion 1151:1159 secretion of a EYFP-fusion of Trop-2-Q118E 1151:1192 We investigated secretion of a EYFP-fusion of Trop-2-Q118E by confocal laser scanning microscopy. 37398215 13 118 theme wild 2122:2125 arg1 cells 2132:2136 wild type cells 2122:2136 wild type cells 2122:2136 The mutant is retained in the secretory pathway in wild type cells and it localises to the cell membrane in UGGT1 -/- single and UGGT1/2 double knock-out cells. 37398215 12 119 theme HEK 1973:1975 arg1 cells 1982:1986 HEK 293T cells 1973:1986 HEK 293T cells 1973:1986 Synopsis Deletion of the UGGT1 and UGGT1/2 genes in HEK 293T cells rescues secretion of an EYFP-fusion of the human Trop-2-Q118E glycoprotein mutant. 37398215 6 120 theme rare 1049:1052 arg1 disease 1054:1060 congenital rare disease 1038:1060 congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins 1038:1132 Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. 37398215 11 121 theme folding 1776:1782 arg1 ERQC 1801:1804 ERQC 1801:1804 ERQC 1801:1804 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 121 theme folding 1776:1782 arg1 Control 1792:1798 ER glycoprotein folding Quality Control 1760:1798 ER glycoprotein folding Quality Control (ERQC) 1760:1805 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 5 122 theme type 808:811 arg1 Trop-2 813:818 the wild type Trop-2 799:818 the wild type Trop-2 799:818 Compared with the wild type Trop-2, which is correctly localised at the plasma membrane, the Trop-2-Q118E variant is found to be heavily retained in the ER. 37398215 3 123 from background 447:456 arg1 gene 510:513 a secreted glycoprotein gene 486:513 a secreted glycoprotein gene 486:513 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 0 124 theme rare-disease 25:36 arg1 secretion 10:18 secretion 10:18 secretion of a rare-disease 10:36 Rescue of secretion of a rare-disease associated mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells. 37398215 11 125 theme ER 1760:1761 arg1 ERQC 1801:1804 ERQC 1801:1804 ERQC 1801:1804 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 125 theme ER 1760:1761 arg1 Control 1792:1798 ER glycoprotein folding Quality Control 1760:1798 ER glycoprotein folding Quality Control (ERQC) 1760:1805 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 6 126 theme therapeutic 1013:1023 arg1 strategy 1025:1032 a rescue-of-secretion therapeutic strategy 991:1032 a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins 991:1132 Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. 37398215 6 126 theme therapeutic 1013:1023 arg1 modulation 977:986 UGGT modulation 972:986 UGGT modulation 972:986 Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. 37398215 3 127 theme mutation 474:481 arg1 background 447:456 the background 443:456 the background of a congenital mutation in a secreted glycoprotein gene 443:513 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 0 128 theme mis-folded 49:58 arg1 glycoprotein 67:78 mis-folded mutant glycoprotein 49:78 mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells 49:113 Rescue of secretion of a rare-disease associated mis-folded mutant glycoprotein in UGGT1 knock-out mammalian cells. 37398215 11 129 theme glycoprotein 1899:1910 arg1 mutants 1912:1918 responsive secreted glycoprotein mutants 1879:1918 responsive secreted glycoprotein mutants 1879:1918 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 130 theme Quality 1784:1790 arg1 ERQC 1801:1804 ERQC 1801:1804 ERQC 1801:1804 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 130 theme Quality 1784:1790 arg1 Control 1792:1798 ER glycoprotein folding Quality Control 1760:1798 ER glycoprotein folding Quality Control (ERQC) 1760:1805 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 131 theme novel 1635:1639 arg1 strategy 1653:1660 a novel therapeutic strategy 1633:1660 a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD 1633:1710 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 9 132 theme membrane 1389:1396 arg1 localisation 1398:1409 The membrane localisation 1385:1409 The membrane localisation of the Trop-2-Q118E-EYFP mutant 1385:1441 The membrane localisation of the Trop-2-Q118E-EYFP mutant was successfully rescued in UGGT1 and UGGT1/2 cells. 37398215 11 133 theme glycoprotein 1763:1774 arg1 ERQC 1801:1804 ERQC 1801:1804 ERQC 1801:1804 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 11 133 theme glycoprotein 1763:1774 arg1 Control 1792:1798 ER glycoprotein folding Quality Control 1760:1798 ER glycoprotein folding Quality Control (ERQC) 1760:1805 The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescue- of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants. 37398215 3 134 theme glycoprotein 497:508 arg1 gene 510:513 a secreted glycoprotein gene 486:513 a secreted glycoprotein gene 486:513 In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). 37398215 1 135 theme secretion 238:246 arg1 checkpoint 248:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 the ER- localised eukaryotic glycoprotein secretion checkpoint 196:257 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 1 135 theme secretion 238:246 arg1 glucosyl-transferase 285:304 UDP-glucose glycoprotein glucosyl-transferase 260:304 UDP-glucose glycoprotein glucosyl-transferase (UGGT) 260:311 Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ER- localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). 37398215 9 136 theme Trop-2-Q118E-EYFP 1418:1434 arg1 mutant 1436:1441 the Trop-2-Q118E-EYFP mutant 1414:1441 the Trop-2-Q118E-EYFP mutant 1414:1441 The membrane localisation of the Trop-2-Q118E-EYFP mutant was successfully rescued in UGGT1 and UGGT1/2 cells. 35652657 15 0 theme env 2821:2823 arg1 gene 2825:2828 gene 2825:2828 gene 2825:2828 Here, we set up a genetic screen to identify the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B. 35652657 3 1 theme domestic 497:504 arg1 cats 506:509 domestic cats 497:509 domestic cats 497:509 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 6 2 theme surface 1123:1129 arg1 downmodulation 1131:1144 cell surface downmodulation 1118:1144 cell surface downmodulation 1118:1144 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 3 3 theme type 534:537 arg1 FeLV-D 542:547 FeLV-D 542:547 FeLV-D 542:547 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 3 3 theme type 534:537 arg1 D 539:539 type D 534:539 feline leukemia virus type D (FeLV-D) 512:548 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 4 4 theme SLC31A1 793:799 arg1 identification 775:788 the identification 771:788 the identification of SLC31A1 encoding the copper transporter 1 (CTR1) as a susceptibility gene for ERV-DC14 infection 771:888 Here, we report the identification of SLC31A1 encoding the copper transporter 1 (CTR1) as a susceptibility gene for ERV-DC14 infection. 35652657 7 5 theme hamster 1350:1356 arg1 cells 1358:1362 feline and hamster cells 1339:1362 cells 1358:1362 We also investigated the role of CTR1 in the nonpermissivity of feline and hamster cells. 35652657 13 6 theme distinct 2361:2368 arg1 diseases 2377:2384 distinct feline diseases 2361:2384 distinct feline diseases 2361:2384 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 3 7 theme leukemia 519:526 arg1 virus 528:532 feline leukemia virus type D (FeLV-D) 512:548 feline leukemia virus type D (FeLV-D) 512:548 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 3 7 theme leukemia 519:526 arg1 virus 586:590 a recombinant virus 572:590 a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor 572:752 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 7 8 theme feline 1339:1344 arg1 cells 1358:1362 feline and hamster cells 1339:1362 cells 1358:1362 We also investigated the role of CTR1 in the nonpermissivity of feline and hamster cells. 35652657 6 9 theme copper 1172:1177 arg1 dose 1164:1167 a high dose 1157:1167 a high dose of copper 1157:1177 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 13 10 theme different 2202:2210 arg1 receptors 2222:2230 different cell host receptors 2202:2230 different cell host receptors 2202:2230 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 9 11 from contrast 1611:1618 arg1 inactive 1638:1645 inactive 1638:1645 inactive 1638:1645 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 11 12 theme endogenous 1846:1855 arg1 type 1868:1871 chimpanzee endogenous retrovirus type 2 1835:1873 chimpanzee endogenous retrovirus type 2 1835:1873 Along with chimpanzee endogenous retrovirus type 2, ERV-DC14 is the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates. 35652657 6 13 theme CTR1 1092:1095 arg1 downmodulation 1131:1144 cell surface downmodulation 1118:1144 cell surface downmodulation 1118:1144 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 6 13 theme CTR1 1092:1095 arg1 inactivation 1076:1087 inactivation 1076:1087 inactivation of CTR1 by genome editing 1076:1113 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 5 14 dep sufficient 945:954 arg1 confer 959:964 confer 959:964 to confer sensitivity to ERV-DC14 pseudotype infection 956:1009 Expression of human CTR1 into nonpermissive cells was sufficient to confer sensitivity to ERV-DC14 pseudotype infection and to increase the binding of an ERV-DC14 Env ligand. 35652657 5 14 dep sufficient 945:954 arg1 increase 1018:1025 increase 1018:1025 to increase the binding of an ERV-DC14 Env ligand 1015:1063 Expression of human CTR1 into nonpermissive cells was sufficient to confer sensitivity to ERV-DC14 pseudotype infection and to increase the binding of an ERV-DC14 Env ligand. 35652657 2 15 theme ERV 280:282 arg1 genes 284:288 ERV genes 280:288 ERV genes like env 280:297 On rare occasions, ERV genes like env are maintained and coopted by hosts for physiological functions, but they also participate in recombination events with exogenous retroviruses to generate rearranged viruses with novel tropisms. 35652657 4 16 theme ERV-DC14 871:878 arg1 infection 880:888 ERV-DC14 infection 871:888 ERV-DC14 infection 871:888 Here, we report the identification of SLC31A1 encoding the copper transporter 1 (CTR1) as a susceptibility gene for ERV-DC14 infection. 35652657 8 17 theme feline 1371:1376 arg1 CTR1 1378:1381 feline CTR1 1371:1381 feline CTR1 1371:1381 While feline CTR1 was fully functional for ERV-DC14, we found that binding was strongly reduced upon treatment with conditioned medium of feline cells, suggesting that the observed resistance to infection was a consequence of CTR1 saturation. 35652657 15 18 theme retroviral 2753:2762 arg1 receptor 2764:2771 the retroviral receptor 2749:2771 the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B 2749:2921 Here, we set up a genetic screen to identify the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B. 35652657 3 19 theme uncharacterized 718:732 arg1 receptor 745:752 a new uncharacterized retroviral receptor 712:752 a new uncharacterized retroviral receptor 712:752 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 11 20 theme retrovirus 1920:1929 arg1 family 1899:1904 the second family 1888:1904 the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates 1888:1991 Along with chimpanzee endogenous retrovirus type 2, ERV-DC14 is the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates. 35652657 11 20 theme retrovirus 1920:1929 arg1 ERV-DC14 1876:1883 ERV-DC14 1876:1883 ERV-DC14 1876:1883 Along with chimpanzee endogenous retrovirus type 2, ERV-DC14 is the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates. 35652657 6 21 theme high 1159:1162 arg1 dose 1164:1167 a high dose 1157:1167 a high dose of copper 1157:1177 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 13 22 theme heme 2319:2322 arg1 FLVCR1 2333:2338 the heme exporter FLVCR1 2315:2338 the heme exporter FLVCR1 2315:2338 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 12 23 theme IMPORTANCE 1994:2003 arg1 usage 2014:2018 IMPORTANCE Receptor usage 1994:2018 IMPORTANCE Receptor usage 1994:2018 IMPORTANCE Receptor usage is an important determinant of diseases induced by pathogenic retroviruses. 35652657 12 23 theme IMPORTANCE 1994:2003 arg1 determinant 2036:2046 an important determinant 2023:2046 an important determinant of diseases induced by pathogenic retroviruses 2023:2093 IMPORTANCE Receptor usage is an important determinant of diseases induced by pathogenic retroviruses. 35652657 5 24 theme pseudotype 990:999 arg1 infection 1001:1009 ERV-DC14 pseudotype infection 981:1009 ERV-DC14 pseudotype infection 981:1009 Expression of human CTR1 into nonpermissive cells was sufficient to confer sensitivity to ERV-DC14 pseudotype infection and to increase the binding of an ERV-DC14 Env ligand. 35652657 8 25 with treatment 1466:1474 arg1 medium 1493:1498 conditioned medium 1481:1498 conditioned medium of feline cells 1481:1514 While feline CTR1 was fully functional for ERV-DC14, we found that binding was strongly reduced upon treatment with conditioned medium of feline cells, suggesting that the observed resistance to infection was a consequence of CTR1 saturation. 35652657 11 26 theme past 1962:1965 arg1 infections 1967:1976 past infections 1962:1976 past infections of vertebrates 1962:1991 Along with chimpanzee endogenous retrovirus type 2, ERV-DC14 is the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates. 35652657 14 27 dep in 2687:2688 arg1 vivo 2690:2693 vivo 2690:2693 vivo 2690:2693 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 13 28 theme exporter 2324:2331 arg1 FLVCR1 2333:2338 the heme exporter FLVCR1 2315:2338 the heme exporter FLVCR1 2315:2338 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 14 29 theme in 2687:2688 arg1 tropism 2695:2701 subsequent in vivo tropism 2676:2701 subsequent in vivo tropism 2676:2701 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 1 30 from genomes 174:180 arg1 hundreds 115:122 hundreds 115:122 hundreds 115:122 Vertebrates harbor hundreds of endogenous retroviral (ERV) sequences in their genomes, which are considered signs of past infections that occurred during evolution. 35652657 1 31 theme retroviral 138:147 arg1 sequences 155:163 endogenous retroviral (ERV) sequences 127:163 endogenous retroviral (ERV) sequences in their genomes 127:180 Vertebrates harbor hundreds of endogenous retroviral (ERV) sequences in their genomes, which are considered signs of past infections that occurred during evolution. 35652657 1 32 theme endogenous 127:136 arg1 sequences 155:163 endogenous retroviral (ERV) sequences 127:163 endogenous retroviral (ERV) sequences in their genomes 127:180 Vertebrates harbor hundreds of endogenous retroviral (ERV) sequences in their genomes, which are considered signs of past infections that occurred during evolution. 35652657 14 33 theme env 2616:2618 arg1 gene 2620:2623 the FeLV-A env gene 2605:2623 the FeLV-A env gene 2605:2623 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 3 34 theme receptor 745:752 arg1 usage 703:707 the usage 699:707 the usage of a new uncharacterized retroviral receptor 699:752 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 3 35 theme recombinant 574:584 arg1 virus 528:532 feline leukemia virus type D (FeLV-D) 512:548 feline leukemia virus type D (FeLV-D) 512:548 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 3 35 theme recombinant 574:584 arg1 virus 586:590 a recombinant virus 572:590 a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor 572:752 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 2 36 with viruses 465:471 arg1 tropisms 484:491 novel tropisms 478:491 novel tropisms 478:491 On rare occasions, ERV genes like env are maintained and coopted by hosts for physiological functions, but they also participate in recombination events with exogenous retroviruses to generate rearranged viruses with novel tropisms. 35652657 1 37 theme ERV 150:152 arg1 sequences 155:163 endogenous retroviral (ERV) sequences 127:163 endogenous retroviral (ERV) sequences in their genomes 127:180 Vertebrates harbor hundreds of endogenous retroviral (ERV) sequences in their genomes, which are considered signs of past infections that occurred during evolution. 35652657 9 38 theme hamster 1621:1627 arg1 CTR1 1629:1632 hamster CTR1 1621:1632 hamster CTR1 1621:1632 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 2 39 theme novel 478:482 arg1 tropisms 484:491 novel tropisms 478:491 novel tropisms 478:491 On rare occasions, ERV genes like env are maintained and coopted by hosts for physiological functions, but they also participate in recombination events with exogenous retroviruses to generate rearranged viruses with novel tropisms. 35652657 0 40 theme Endogenous 64:73 arg1 Retrovirus 75:84 Feline Endogenous Retrovirus ERV-DC14 57:93 Feline Endogenous Retrovirus ERV-DC14 57:93 Identification of Copper Transporter 1 as a Receptor for Feline Endogenous Retrovirus ERV-DC14. 35652657 16 41 theme copper 2952:2957 arg1 CTR1 2971:2974 the copper transporter CTR1 2948:2974 the copper transporter CTR1 2948:2974 Our results reveal that the copper transporter CTR1 was such a receptor and provide new insights into the acquisition of an expanded tropism by FeLV-D. 35652657 16 41 theme copper 2952:2957 arg1 receptor 2987:2994 such a receptor 2980:2994 such a receptor 2980:2994 Our results reveal that the copper transporter CTR1 was such a receptor and provide new insights into the acquisition of an expanded tropism by FeLV-D. 35652657 1 42 theme sequences 155:163 arg1 hundreds 115:122 hundreds 115:122 hundreds 115:122 Vertebrates harbor hundreds of endogenous retroviral (ERV) sequences in their genomes, which are considered signs of past infections that occurred during evolution. 35652657 9 43 theme glycosylation 1681:1693 arg1 site 1695:1698 a N-linked glycosylation site 1670:1698 a N-linked glycosylation site 1670:1698 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 9 43 theme glycosylation 1681:1693 arg1 absent 1725:1730 absent 1725:1730 absent 1725:1730 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 16 44 theme tropism 3057:3063 arg1 acquisition 3030:3040 the acquisition 3026:3040 the acquisition of an expanded tropism by FeLV-D 3026:3073 Our results reveal that the copper transporter CTR1 was such a receptor and provide new insights into the acquisition of an expanded tropism by FeLV-D. 35652657 14 45 theme subsequent 2676:2685 arg1 tropism 2695:2701 subsequent in vivo tropism 2676:2701 subsequent in vivo tropism 2676:2701 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 5 46 theme CTR1 911:914 arg1 Expression 891:900 Expression 891:900 Expression of human CTR1 into nonpermissive cells 891:939 Expression of human CTR1 into nonpermissive cells was sufficient to confer sensitivity to ERV-DC14 pseudotype infection and to increase the binding of an ERV-DC14 Env ligand. 35652657 5 47 theme Env 1054:1056 arg1 ligand 1058:1063 an ERV-DC14 Env ligand 1042:1063 an ERV-DC14 Env ligand 1042:1063 Expression of human CTR1 into nonpermissive cells was sufficient to confer sensitivity to ERV-DC14 pseudotype infection and to increase the binding of an ERV-DC14 Env ligand. 35652657 5 48 theme nonpermissive 921:933 arg1 cells 935:939 nonpermissive cells 921:939 nonpermissive cells 921:939 Expression of human CTR1 into nonpermissive cells was sufficient to confer sensitivity to ERV-DC14 pseudotype infection and to increase the binding of an ERV-DC14 Env ligand. 35652657 15 49 theme genetic 2722:2728 arg1 screen 2730:2735 a genetic screen 2720:2735 a genetic screen 2720:2735 Here, we set up a genetic screen to identify the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B. 35652657 13 50 theme leukemia 2118:2125 arg1 viruses 2127:2133 feline leukemia viruses 2111:2133 feline leukemia viruses 2111:2133 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 13 50 theme leukemia 2118:2125 arg1 subgroups 2142:2150 three subgroups 2136:2150 three subgroups (A, B, and C) based on their ability to recognize different cell host receptors 2136:2230 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 1 51 from hundreds 115:122 arg1 genomes 174:180 their genomes 168:180 their genomes 168:180 Vertebrates harbor hundreds of endogenous retroviral (ERV) sequences in their genomes, which are considered signs of past infections that occurred during evolution. 35652657 15 52 theme endogenous 2795:2804 arg1 provirus 2806:2813 a feline endogenous provirus 2786:2813 a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B 2786:2921 Here, we set up a genetic screen to identify the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B. 35652657 15 52 theme endogenous 2795:2804 arg1 ERV-DC14 2776:2783 ERV-DC14 2776:2783 ERV-DC14 2776:2783 Here, we set up a genetic screen to identify the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B. 35652657 13 53 dep subgroups 2142:2150 arg1 A 2153:2153 A 2153:2153 A 2153:2153 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 13 53 dep subgroups 2142:2150 arg1 subgroups 2142:2150 three subgroups 2136:2150 three subgroups (A, B, and C) based on their ability to recognize different cell host receptors 2136:2230 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 13 53 dep subgroups 2142:2150 arg1 B 2156:2156 B 2156:2156 B 2156:2156 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 13 53 dep subgroups 2142:2150 arg1 C 2163:2163 C 2163:2163 C 2163:2163 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 2 54 theme recombination 393:405 arg1 events 407:412 recombination events 393:412 recombination events with exogenous retroviruses 393:440 On rare occasions, ERV genes like env are maintained and coopted by hosts for physiological functions, but they also participate in recombination events with exogenous retroviruses to generate rearranged viruses with novel tropisms. 35652657 0 55 theme Copper 18:23 arg1 Transporter 25:35 Copper Transporter 1 18:37 Copper Transporter 1 18:37 Identification of Copper Transporter 1 as a Receptor for Feline Endogenous Retrovirus ERV-DC14. 35652657 3 56 theme feline 512:517 arg1 virus 528:532 feline leukemia virus type D (FeLV-D) 512:548 feline leukemia virus type D (FeLV-D) 512:548 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 3 56 theme feline 512:517 arg1 virus 586:590 a recombinant virus 572:590 a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor 572:752 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 8 57 theme conditioned 1481:1491 arg1 medium 1493:1498 conditioned medium 1481:1498 conditioned medium of feline cells 1481:1514 While feline CTR1 was fully functional for ERV-DC14, we found that binding was strongly reduced upon treatment with conditioned medium of feline cells, suggesting that the observed resistance to infection was a consequence of CTR1 saturation. 35652657 13 58 theme phosphate 2283:2291 arg1 PiT1 2305:2308 the phosphate transporter PiT1 2279:2308 the phosphate transporter PiT1 2279:2308 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 15 59 theme infectious 2851:2860 arg1 FeLV-A 2862:2867 infectious FeLV-A 2851:2867 infectious FeLV-A 2851:2867 Here, we set up a genetic screen to identify the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B. 35652657 14 60 theme retroviral 2561:2570 arg1 sequences 2576:2584 endogenous retroviral env sequences 2550:2584 endogenous retroviral env sequences 2550:2584 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 3 61 theme infectious 604:613 arg1 FeLV-A 615:620 infectious FeLV-A 604:620 infectious FeLV-A 604:620 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 5 62 theme ERV-DC14 981:988 arg1 infection 1001:1009 ERV-DC14 pseudotype infection 981:1009 ERV-DC14 pseudotype infection 981:1009 Expression of human CTR1 into nonpermissive cells was sufficient to confer sensitivity to ERV-DC14 pseudotype infection and to increase the binding of an ERV-DC14 Env ligand. 35652657 8 63 theme cells 1510:1514 arg1 medium 1493:1498 conditioned medium 1481:1498 conditioned medium of feline cells 1481:1514 While feline CTR1 was fully functional for ERV-DC14, we found that binding was strongly reduced upon treatment with conditioned medium of feline cells, suggesting that the observed resistance to infection was a consequence of CTR1 saturation. 35652657 3 64 theme env 646:648 arg1 gene 650:653 likely the ERV-DC14 env gene 626:653 likely the ERV-DC14 env gene 626:653 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 12 65 theme diseases 2051:2058 arg1 usage 2014:2018 IMPORTANCE Receptor usage 1994:2018 IMPORTANCE Receptor usage 1994:2018 IMPORTANCE Receptor usage is an important determinant of diseases induced by pathogenic retroviruses. 35652657 12 65 theme diseases 2051:2058 arg1 determinant 2036:2046 an important determinant 2023:2046 an important determinant of diseases induced by pathogenic retroviruses 2023:2093 IMPORTANCE Receptor usage is an important determinant of diseases induced by pathogenic retroviruses. 35652657 12 66 theme pathogenic 2071:2080 arg1 retroviruses 2082:2093 pathogenic retroviruses 2071:2093 pathogenic retroviruses 2071:2093 IMPORTANCE Receptor usage is an important determinant of diseases induced by pathogenic retroviruses. 35652657 11 67 theme second 1892:1897 arg1 family 1899:1904 the second family 1888:1904 the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates 1888:1991 Along with chimpanzee endogenous retrovirus type 2, ERV-DC14 is the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates. 35652657 11 67 theme second 1892:1897 arg1 ERV-DC14 1876:1883 ERV-DC14 1876:1883 ERV-DC14 1876:1883 Along with chimpanzee endogenous retrovirus type 2, ERV-DC14 is the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates. 35652657 9 68 from presence 1658:1665 arg1 position 1703:1710 position 27 1703:1713 position 27 1703:1713 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 13 69 theme host 2217:2220 arg1 receptors 2222:2230 different cell host receptors 2202:2230 different cell host receptors 2202:2230 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 15 70 theme ERV-DC14 2776:2783 arg1 receptor 2764:2771 the retroviral receptor 2749:2771 the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B 2749:2921 Here, we set up a genetic screen to identify the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B. 35652657 2 71 theme physiological 339:351 arg1 functions 353:361 physiological functions 339:361 physiological functions 339:361 On rare occasions, ERV genes like env are maintained and coopted by hosts for physiological functions, but they also participate in recombination events with exogenous retroviruses to generate rearranged viruses with novel tropisms. 35652657 3 72 dep FeLV-A 615:620 arg1 the 600:602 the 600:602 the 600:602 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 8 73 theme saturation 1596:1605 arg1 consequence 1576:1586 a consequence 1574:1586 a consequence of CTR1 saturation 1574:1605 While feline CTR1 was fully functional for ERV-DC14, we found that binding was strongly reduced upon treatment with conditioned medium of feline cells, suggesting that the observed resistance to infection was a consequence of CTR1 saturation. 35652657 8 73 theme saturation 1596:1605 arg1 resistance 1546:1555 the observed resistance 1533:1555 the observed resistance to infection 1533:1568 While feline CTR1 was fully functional for ERV-DC14, we found that binding was strongly reduced upon treatment with conditioned medium of feline cells, suggesting that the observed resistance to infection was a consequence of CTR1 saturation. 35652657 14 74 dep emerged 2493:2499 arg1 leading 2631:2637 leading 2631:2637 leading to a switch in receptor usage and in subsequent in vivo tropism 2631:2701 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 9 75 from absent 1725:1730 arg1 ortholog 1745:1752 the human ortholog 1735:1752 the human ortholog 1735:1752 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 4 76 theme copper 814:819 arg1 transporter 821:831 the copper transporter 1 810:833 the copper transporter 1 (CTR1) 810:840 Here, we report the identification of SLC31A1 encoding the copper transporter 1 (CTR1) as a susceptibility gene for ERV-DC14 infection. 35652657 4 76 theme copper 814:819 arg1 CTR1 836:839 CTR1 836:839 CTR1 836:839 Here, we report the identification of SLC31A1 encoding the copper transporter 1 (CTR1) as a susceptibility gene for ERV-DC14 infection. 35652657 6 77 theme genome 1100:1105 arg1 editing 1107:1113 genome editing 1100:1113 genome editing 1100:1113 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 14 78 theme infected 2449:2456 arg1 cats 2458:2461 all naturally infected cats 2435:2461 all naturally infected cats 2435:2461 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 6 79 theme cell 1118:1121 arg1 downmodulation 1131:1144 cell surface downmodulation 1118:1144 cell surface downmodulation 1118:1144 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 3 80 theme due 692:694 arg1 tropism 684:690 an extended tropism 672:690 an extended tropism due to the usage of a new uncharacterized retroviral receptor 672:752 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 6 81 theme ERV-DC14 1202:1209 arg1 infection 1211:1219 ERV-DC14 infection 1202:1219 ERV-DC14 infection 1202:1219 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 2 82 theme rare 264:267 arg1 occasions 269:277 rare occasions 264:277 rare occasions 264:277 On rare occasions, ERV genes like env are maintained and coopted by hosts for physiological functions, but they also participate in recombination events with exogenous retroviruses to generate rearranged viruses with novel tropisms. 35652657 7 83 theme cells 1358:1362 arg1 nonpermissivity 1320:1334 the nonpermissivity 1316:1334 the nonpermissivity of feline and hamster cells 1316:1362 We also investigated the role of CTR1 in the nonpermissivity of feline and hamster cells. 35652657 3 84 theme extended 675:682 arg1 tropism 684:690 an extended tropism 672:690 an extended tropism due to the usage of a new uncharacterized retroviral receptor 672:752 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 13 85 theme feline 2370:2375 arg1 diseases 2377:2384 distinct feline diseases 2361:2384 distinct feline diseases 2361:2384 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 14 86 from switch 2644:2649 arg1 usage 2663:2667 receptor usage 2654:2667 receptor usage 2654:2667 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 14 86 from switch 2644:2649 arg1 tropism 2695:2701 subsequent in vivo tropism 2676:2701 subsequent in vivo tropism 2676:2701 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 9 87 link N-linked 1672:1679 arg1 site 1695:1698 a N-linked glycosylation site 1670:1698 a N-linked glycosylation site 1670:1698 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 9 87 link N-linked 1672:1679 arg1 absent 1725:1730 absent 1725:1730 absent 1725:1730 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 12 88 theme important 2026:2034 arg1 usage 2014:2018 IMPORTANCE Receptor usage 1994:2018 IMPORTANCE Receptor usage 1994:2018 IMPORTANCE Receptor usage is an important determinant of diseases induced by pathogenic retroviruses. 35652657 12 88 theme important 2026:2034 arg1 determinant 2036:2046 an important determinant 2023:2046 an important determinant of diseases induced by pathogenic retroviruses 2023:2093 IMPORTANCE Receptor usage is an important determinant of diseases induced by pathogenic retroviruses. 35652657 13 89 theme thiamine 2251:2258 arg1 THTR1 2272:2276 the thiamine transporter THTR1 2247:2276 the thiamine transporter THTR1 2247:2276 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 11 90 theme endogenous 1909:1918 arg1 retrovirus 1920:1929 endogenous retrovirus 1909:1929 endogenous retrovirus 1909:1929 Along with chimpanzee endogenous retrovirus type 2, ERV-DC14 is the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates. 35652657 14 91 theme receptor 2654:2661 arg1 usage 2663:2667 receptor usage 2654:2667 receptor usage 2654:2667 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 4 92 theme susceptibility 847:860 arg1 gene 862:865 a susceptibility gene 845:865 a susceptibility gene for ERV-DC14 infection 845:888 Here, we report the identification of SLC31A1 encoding the copper transporter 1 (CTR1) as a susceptibility gene for ERV-DC14 infection. 35652657 11 93 theme retrovirus 1857:1866 arg1 type 1868:1871 chimpanzee endogenous retrovirus type 2 1835:1873 chimpanzee endogenous retrovirus type 2 1835:1873 Along with chimpanzee endogenous retrovirus type 2, ERV-DC14 is the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates. 35652657 12 94 theme Receptor 2005:2012 arg1 usage 2014:2018 IMPORTANCE Receptor usage 1994:2018 IMPORTANCE Receptor usage 1994:2018 IMPORTANCE Receptor usage is an important determinant of diseases induced by pathogenic retroviruses. 35652657 12 94 theme Receptor 2005:2012 arg1 determinant 2036:2046 an important determinant 2023:2046 an important determinant of diseases induced by pathogenic retroviruses 2023:2093 IMPORTANCE Receptor usage is an important determinant of diseases induced by pathogenic retroviruses. 35652657 3 95 theme retroviral 734:743 arg1 receptor 745:752 a new uncharacterized retroviral receptor 712:752 a new uncharacterized retroviral receptor 712:752 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 11 96 theme chimpanzee 1835:1844 arg1 type 1868:1871 chimpanzee endogenous retrovirus type 2 1835:1873 chimpanzee endogenous retrovirus type 2 1835:1873 Along with chimpanzee endogenous retrovirus type 2, ERV-DC14 is the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates. 35652657 2 97 with events 407:412 arg1 retroviruses 429:440 exogenous retroviruses 419:440 exogenous retroviruses 419:440 On rare occasions, ERV genes like env are maintained and coopted by hosts for physiological functions, but they also participate in recombination events with exogenous retroviruses to generate rearranged viruses with novel tropisms. 35652657 11 98 theme vertebrates 1981:1991 arg1 infections 1967:1976 past infections 1962:1976 past infections of vertebrates 1962:1991 Along with chimpanzee endogenous retrovirus type 2, ERV-DC14 is the second family of endogenous retrovirus known to have used CTR1 during past infections of vertebrates. 35652657 7 99 theme CTR1 1308:1311 arg1 role 1300:1303 the role 1296:1303 the role of CTR1 in the nonpermissivity of feline and hamster cells 1296:1362 We also investigated the role of CTR1 in the nonpermissivity of feline and hamster cells. 35652657 3 100 theme new 714:716 arg1 receptor 745:752 a new uncharacterized retroviral receptor 712:752 a new uncharacterized retroviral receptor 712:752 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 6 101 theme magnesium 1240:1248 arg1 treatment 1250:1258 magnesium treatment 1240:1258 magnesium treatment 1240:1258 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 16 102 theme new 3008:3010 arg1 insights 3012:3019 new insights 3008:3019 new insights into the acquisition of an expanded tropism by FeLV-D 3008:3073 Our results reveal that the copper transporter CTR1 was such a receptor and provide new insights into the acquisition of an expanded tropism by FeLV-D. 35652657 3 103 dep virus 528:532 arg1 FeLV-D 542:547 FeLV-D 542:547 FeLV-D 542:547 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 3 103 dep virus 528:532 arg1 D 539:539 type D 534:539 feline leukemia virus type D (FeLV-D) 512:548 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 9 104 from ortholog 1745:1752 arg1 site 1695:1698 a N-linked glycosylation site 1670:1698 a N-linked glycosylation site 1670:1698 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 9 104 from ortholog 1745:1752 arg1 absent 1725:1730 absent 1725:1730 absent 1725:1730 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 14 105 with recombination 2531:2543 arg1 sequences 2576:2584 endogenous retroviral env sequences 2550:2584 endogenous retroviral env sequences 2550:2584 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 6 106 theme CTR1 1149:1152 arg1 downmodulation 1131:1144 cell surface downmodulation 1118:1144 cell surface downmodulation 1118:1144 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 6 106 theme CTR1 1149:1152 arg1 inactivation 1076:1087 inactivation 1076:1087 inactivation of CTR1 by genome editing 1076:1113 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 0 107 theme Feline 57:62 arg1 Retrovirus 75:84 Feline Endogenous Retrovirus ERV-DC14 57:93 Feline Endogenous Retrovirus ERV-DC14 57:93 Identification of Copper Transporter 1 as a Receptor for Feline Endogenous Retrovirus ERV-DC14. 35652657 9 108 gly glycosylation 1681:1693 arg2 position 1703:1710 position 27 1703:1713 position 27 1703:1713 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 9 108 gly glycosylation 1681:1693 arg2 site 1695:1698 a N-linked glycosylation site 1670:1698 a N-linked glycosylation site 1670:1698 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 9 108 gly glycosylation 1681:1693 arg2 absent 1725:1730 absent 1725:1730 absent 1725:1730 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 9 109 from inactive 1638:1645 arg1 contrast 1611:1618 contrast 1611:1618 contrast 1611:1618 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 16 110 theme expanded 3048:3055 arg1 tropism 3057:3063 an expanded tropism 3045:3063 an expanded tropism 3045:3063 Our results reveal that the copper transporter CTR1 was such a receptor and provide new insights into the acquisition of an expanded tropism by FeLV-D. 35652657 14 111 theme FeLV-A 2609:2614 arg1 gene 2620:2623 the FeLV-A env gene 2605:2623 the FeLV-A env gene 2605:2623 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 9 112 theme N-linked 1672:1679 arg1 site 1695:1698 a N-linked glycosylation site 1670:1698 a N-linked glycosylation site 1670:1698 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 9 112 theme N-linked 1672:1679 arg1 absent 1725:1730 absent 1725:1730 absent 1725:1730 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 1 113 from sequences 155:163 arg1 genomes 174:180 their genomes 168:180 their genomes 168:180 Vertebrates harbor hundreds of endogenous retroviral (ERV) sequences in their genomes, which are considered signs of past infections that occurred during evolution. 35652657 5 114 theme human 905:909 arg1 CTR1 911:914 human CTR1 905:914 human CTR1 905:914 Expression of human CTR1 into nonpermissive cells was sufficient to confer sensitivity to ERV-DC14 pseudotype infection and to increase the binding of an ERV-DC14 Env ligand. 35652657 6 115 contain had 1260:1262 arg1 treatment 1250:1258 magnesium treatment 1240:1258 magnesium treatment 1240:1258 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 6 115 contain had 1260:1262 arg2 effect 1267:1272 no effect 1264:1272 no effect 1264:1272 Moreover, inactivation of CTR1 by genome editing or cell surface downmodulation of CTR1 by a high dose of copper dramatically decreased ERV-DC14 infection and binding, while magnesium treatment had no effect. 35652657 15 116 theme similar 2905:2911 arg1 process 2897:2903 a process 2895:2903 a process similar to FeLV-B 2895:2921 Here, we set up a genetic screen to identify the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B. 35652657 9 117 theme site 1695:1698 arg1 presence 1658:1665 the presence 1654:1665 the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog 1654:1752 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 13 118 theme transporter 2293:2303 arg1 PiT1 2305:2308 the phosphate transporter PiT1 2279:2308 the phosphate transporter PiT1 2279:2308 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 14 119 from mutations 2592:2600 arg1 gene 2620:2623 the FeLV-A env gene 2605:2623 the FeLV-A env gene 2605:2623 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 5 120 theme ERV-DC14 1045:1052 arg1 ligand 1058:1063 an ERV-DC14 Env ligand 1042:1063 an ERV-DC14 Env ligand 1042:1063 Expression of human CTR1 into nonpermissive cells was sufficient to confer sensitivity to ERV-DC14 pseudotype infection and to increase the binding of an ERV-DC14 Env ligand. 35652657 16 121 theme transporter 2959:2969 arg1 CTR1 2971:2974 the copper transporter CTR1 2948:2974 the copper transporter CTR1 2948:2974 Our results reveal that the copper transporter CTR1 was such a receptor and provide new insights into the acquisition of an expanded tropism by FeLV-D. 35652657 16 121 theme transporter 2959:2969 arg1 receptor 2987:2994 such a receptor 2980:2994 such a receptor 2980:2994 Our results reveal that the copper transporter CTR1 was such a receptor and provide new insights into the acquisition of an expanded tropism by FeLV-D. 35652657 5 122 theme ligand 1058:1063 arg1 binding 1031:1037 the binding 1027:1037 the binding of an ERV-DC14 Env ligand 1027:1063 Expression of human CTR1 into nonpermissive cells was sufficient to confer sensitivity to ERV-DC14 pseudotype infection and to increase the binding of an ERV-DC14 Env ligand. 35652657 13 123 theme transporter 2260:2270 arg1 THTR1 2272:2276 the thiamine transporter THTR1 2247:2276 the thiamine transporter THTR1 2247:2276 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 7 124 from role 1300:1303 arg1 nonpermissivity 1320:1334 the nonpermissivity 1316:1334 the nonpermissivity of feline and hamster cells 1316:1362 We also investigated the role of CTR1 in the nonpermissivity of feline and hamster cells. 35652657 15 125 theme feline 2788:2793 arg1 provirus 2806:2813 a feline endogenous provirus 2786:2813 a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B 2786:2921 Here, we set up a genetic screen to identify the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B. 35652657 15 125 theme feline 2788:2793 arg1 ERV-DC14 2776:2783 ERV-DC14 2776:2783 ERV-DC14 2776:2783 Here, we set up a genetic screen to identify the retroviral receptor of ERV-DC14, a feline endogenous provirus whose env gene has been captured by infectious FeLV-A to give rise to FeLV-D in a process similar to FeLV-B. 35652657 2 126 theme exogenous 419:427 arg1 retroviruses 429:440 exogenous retroviruses 419:440 exogenous retroviruses 419:440 On rare occasions, ERV genes like env are maintained and coopted by hosts for physiological functions, but they also participate in recombination events with exogenous retroviruses to generate rearranged viruses with novel tropisms. 35652657 0 127 theme Transporter 25:35 arg1 Identification 0:13 Identification 0:13 Identification of Copper Transporter 1 as a Receptor for Feline Endogenous Retrovirus ERV-DC14. 0:94 Identification of Copper Transporter 1 as a Receptor for Feline Endogenous Retrovirus ERV-DC14. 35652657 13 128 theme viruses 2127:2133 arg1 case 2103:2106 the case 2099:2106 the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively 2099:2244 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 9 129 from position 1703:1710 arg1 site 1695:1698 a N-linked glycosylation site 1670:1698 a N-linked glycosylation site 1670:1698 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 9 129 from position 1703:1710 arg1 presence 1658:1665 the presence 1654:1665 the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog 1654:1752 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 9 129 from position 1703:1710 arg1 absent 1725:1730 absent 1725:1730 absent 1725:1730 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 14 130 theme env 2572:2574 arg1 sequences 2576:2584 endogenous retroviral env sequences 2550:2584 endogenous retroviral env sequences 2550:2584 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 2 131 theme rearranged 454:463 arg1 viruses 465:471 rearranged viruses 454:471 rearranged viruses with novel tropisms 454:491 On rare occasions, ERV genes like env are maintained and coopted by hosts for physiological functions, but they also participate in recombination events with exogenous retroviruses to generate rearranged viruses with novel tropisms. 35652657 8 132 theme feline 1503:1508 arg1 cells 1510:1514 feline cells 1503:1514 feline cells 1503:1514 While feline CTR1 was fully functional for ERV-DC14, we found that binding was strongly reduced upon treatment with conditioned medium of feline cells, suggesting that the observed resistance to infection was a consequence of CTR1 saturation. 35652657 1 133 theme infections 218:227 arg1 signs 204:208 signs 204:208 signs of past infections that occurred during evolution 204:258 Vertebrates harbor hundreds of endogenous retroviral (ERV) sequences in their genomes, which are considered signs of past infections that occurred during evolution. 35652657 14 134 theme endogenous 2550:2559 arg1 sequences 2576:2584 endogenous retroviral env sequences 2550:2584 endogenous retroviral env sequences 2550:2584 FeLV-A is horizontally transmitted and found in all naturally infected cats, while FeLV-B and FeLV-C have emerged from FeLV-A, respectively, by recombination with endogenous retroviral env sequences or by mutations in the FeLV-A env gene, both leading to a switch in receptor usage and in subsequent in vivo tropism. 35652657 9 135 theme human 1739:1743 arg1 ortholog 1745:1752 the human ortholog 1735:1752 the human ortholog 1735:1752 In contrast, hamster CTR1 was inactive due to the presence of a N-linked glycosylation site at position 27, which is absent in the human ortholog. 35652657 3 136 theme ERV-DC14 637:644 arg1 gene 650:653 likely the ERV-DC14 env gene 626:653 likely the ERV-DC14 env gene 626:653 In domestic cats, feline leukemia virus type D (FeLV-D) has been described as a recombinant virus between the infectious FeLV-A and likely the ERV-DC14 env gene that resulted in an extended tropism due to the usage of a new uncharacterized retroviral receptor. 35652657 13 137 theme feline 2111:2116 arg1 viruses 2127:2133 feline leukemia viruses 2111:2133 feline leukemia viruses 2111:2133 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 13 137 theme feline 2111:2116 arg1 subgroups 2142:2150 three subgroups 2136:2150 three subgroups (A, B, and C) based on their ability to recognize different cell host receptors 2136:2230 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 13 138 theme cell 2212:2215 arg1 receptors 2222:2230 different cell host receptors 2202:2230 different cell host receptors 2202:2230 In the case of feline leukemia viruses, three subgroups (A, B, and C) based on their ability to recognize different cell host receptors, respectively, the thiamine transporter THTR1, the phosphate transporter PiT1, and the heme exporter FLVCR1, are associated with distinct feline diseases. 35652657 8 139 theme CTR1 1591:1594 arg1 saturation 1596:1605 CTR1 saturation 1591:1605 CTR1 saturation 1591:1605 While feline CTR1 was fully functional for ERV-DC14, we found that binding was strongly reduced upon treatment with conditioned medium of feline cells, suggesting that the observed resistance to infection was a consequence of CTR1 saturation. 35652657 1 140 theme past 213:216 arg1 infections 218:227 past infections 213:227 past infections 213:227 Vertebrates harbor hundreds of endogenous retroviral (ERV) sequences in their genomes, which are considered signs of past infections that occurred during evolution. 35652657 8 141 theme observed 1537:1544 arg1 consequence 1576:1586 a consequence 1574:1586 a consequence of CTR1 saturation 1574:1605 While feline CTR1 was fully functional for ERV-DC14, we found that binding was strongly reduced upon treatment with conditioned medium of feline cells, suggesting that the observed resistance to infection was a consequence of CTR1 saturation. 35652657 8 141 theme observed 1537:1544 arg1 resistance 1546:1555 the observed resistance 1533:1555 the observed resistance to infection 1533:1568 While feline CTR1 was fully functional for ERV-DC14, we found that binding was strongly reduced upon treatment with conditioned medium of feline cells, suggesting that the observed resistance to infection was a consequence of CTR1 saturation. 36345035 7 0 theme ERK2 1428:1431 arg1 signaling 1433:1441 ERK1 and ERK2 signaling 1419:1441 ERK1 and ERK2 signaling 1419:1441 RESULTS Focusing on the DCM versus HCM contrast (DCMvsHCM), we identified 201 differentially expressed genes, some of which can be clearly associated with changes in ERK1 and ERK2 signaling. 36345035 13 1 dep https 2510:2514 arg1 //github.com/AnnekathrinSilvia/magnetique 2516:2556 //github.com/AnnekathrinSilvia/magnetique 2516:2556 https://github.com/AnnekathrinSilvia/magnetique 2510:2556 The source code for both the analyses ( https://github.com/dieterich-lab/magnetiqueCode2022 ) and the web application ( https://github.com/AnnekathrinSilvia/magnetique ) is available to the public. 36345035 12 2 theme HF 2268:2269 arg1 transcriptome 2271:2283 the HF transcriptome 2264:2283 the HF transcriptome 2264:2283 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 7 3 theme ERK1 1419:1422 arg1 signaling 1433:1441 ERK1 and ERK2 signaling 1419:1441 ERK1 and ERK2 signaling 1419:1441 RESULTS Focusing on the DCM versus HCM contrast (DCMvsHCM), we identified 201 differentially expressed genes, some of which can be clearly associated with changes in ERK1 and ERK2 signaling. 36345035 13 4 dep application 2496:2506 arg1 https 2510:2514 https 2510:2514 https://github.com/AnnekathrinSilvia/magnetique 2510:2556 The source code for both the analyses ( https://github.com/dieterich-lab/magnetiqueCode2022 ) and the web application ( https://github.com/AnnekathrinSilvia/magnetique ) is available to the public. 36345035 1 5 theme medical 257:263 arg1 researchers 265:275 medical researchers 257:275 medical researchers 257:275 BACKGROUND Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. 36345035 4 6 theme expression 822:831 arg1 signatures 853:862 differential gene expression, associated pathway signatures 804:862 signatures 853:862 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 3 7 theme available 529:537 arg1 datasets 539:546 available datasets 529:546 available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy 529:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 4 8 theme associated 834:843 arg1 signatures 853:862 differential gene expression, associated pathway signatures 804:862 signatures 853:862 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 3 9 theme samples 576:582 arg1 datasets 539:546 available datasets 529:546 available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy 529:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 9 theme samples 576:582 arg1 NFD 696:698 NFD 696:698 NFD 696:698 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 9 theme samples 576:582 arg1 hearts 688:693 unmatched non-failing hearts 666:693 unmatched non-failing hearts (NFD) 666:699 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 11 10 theme target 2002:2007 arg1 networks 2021:2028 target interaction networks 2002:2028 target interaction networks 2002:2028 Moreover, we reconstruct RBP - target interaction networks and showcase the examples of CPEB1, which is differentially expressed in the DCMvsHCM contrast. 36345035 4 11 theme transcription 917:929 arg1 activities 938:947 inferred transcription factor activities 908:947 inferred transcription factor activities 908:947 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 7 12 theme expressed 1346:1354 arg1 genes 1356:1360 201 differentially expressed genes 1327:1360 201 differentially expressed genes 1327:1360 RESULTS Focusing on the DCM versus HCM contrast (DCMvsHCM), we identified 201 differentially expressed genes, some of which can be clearly associated with changes in ERK1 and ERK2 signaling. 36345035 11 13 theme interaction 2009:2019 arg1 networks 2021:2028 target interaction networks 2002:2028 target interaction networks 2002:2028 Moreover, we reconstruct RBP - target interaction networks and showcase the examples of CPEB1, which is differentially expressed in the DCMvsHCM contrast. 36345035 3 14 theme organ 706:710 arg1 donors 712:717 organ donors 706:717 organ donors 706:717 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 15 theme ventricular 556:566 arg1 samples 576:582 left ventricular RNA-seq samples 551:582 left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy 551:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 12 16 theme interaction 2368:2378 arg1 networks 2380:2387 transcription factor signaling and RBP:RNA interaction networks 2325:2387 networks 2380:2387 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 10 17 theme common 1869:1874 arg1 modification 1895:1906 a common post-translational modification 1867:1906 a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy 1867:1968 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 12 18 theme factor 2339:2344 arg1 signaling 2346:2354 transcription factor signaling and RBP:RNA interaction networks 2325:2387 signaling 2346:2354 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 3 19 from hearts 688:693 arg1 patients 589:596 patients 589:596 patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy 589:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 5 20 theme RNA 1044:1046 arg1 changes 1079:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 1 21 theme recent 118:123 arg1 increase 125:132 a recent increase 116:132 a recent increase in the number of RNA-seq datasets investigating heart failure (HF) 116:199 BACKGROUND Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. 36345035 12 22 theme online 2211:2216 arg1 application 2218:2228 the first online application 2201:2228 the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks 2201:2387 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 12 22 theme online 2211:2216 arg1 Magnetique 2137:2146 CONCLUSION Magnetique 2126:2146 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) 2126:2196 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 3 23 theme confounding 772:782 arg1 factors 784:790 model confounding factors 766:790 model confounding factors 766:790 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 5 24 theme isoform 1059:1065 arg1 changes 1079:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 14 25 theme failure 2673:2679 arg1 basis 2658:2662 the molecular basis 2644:2662 the molecular basis of heart failure 2644:2679 We hope that our application will help users to uncover the molecular basis of heart failure. 36345035 1 26 dep BACKGROUND 97:106 arg1 increase 125:132 a recent increase 116:132 a recent increase in the number of RNA-seq datasets investigating heart failure (HF) 116:199 BACKGROUND Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. 36345035 0 27 theme transcriptome 54:66 arg1 signatures 68:77 transcriptome signatures 54:77 transcriptome signatures of heart failure 54:94 Magnetique: an interactive web application to explore transcriptome signatures of heart failure. 36345035 12 28 dep https 2150:2154 arg1 //shiny.dieterichlab.org/app/magnetique 2156:2194 //shiny.dieterichlab.org/app/magnetique 2156:2194 https://shiny.dieterichlab.org/app/magnetique 2150:2194 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 10 29 theme post-translational 1876:1893 arg1 modification 1895:1906 a common post-translational modification 1867:1906 a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy 1867:1968 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 6 30 dep comparisons 1224:1234 arg1 NFD 1247:1249 NFD 1247:1249 NFD 1247:1249 We report results for all pairwise comparisons (DCM, HCM, NFD). 36345035 6 30 dep comparisons 1224:1234 arg1 HCM 1242:1244 HCM 1242:1244 HCM 1242:1244 We report results for all pairwise comparisons (DCM, HCM, NFD). 36345035 6 30 dep comparisons 1224:1234 arg1 DCM 1237:1239 DCM 1237:1239 DCM 1237:1239 We report results for all pairwise comparisons (DCM, HCM, NFD). 36345035 10 31 theme heart 1930:1934 arg1 arrhythmias 1936:1946 heart arrhythmias 1930:1946 heart arrhythmias 1930:1946 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 3 32 theme model 766:770 arg1 factors 784:790 model confounding factors 766:790 model confounding factors 766:790 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 1 33 theme RNA-seq 151:157 arg1 datasets 159:166 RNA-seq datasets 151:166 RNA-seq datasets investigating heart failure (HF) 151:199 BACKGROUND Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. 36345035 4 34 theme integer 957:963 arg1 programming 972:982 integer linear programming 957:982 integer linear programming 957:982 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 0 35 theme failure 88:94 arg1 signatures 68:77 transcriptome signatures 54:77 transcriptome signatures of heart failure 54:94 Magnetique: an interactive web application to explore transcriptome signatures of heart failure. 36345035 2 36 theme heart 392:396 arg1 failure 398:404 heart failure 392:404 heart failure 392:404 We address the need for an intuitive and interactive web application to explore the transcriptional signatures of heart failure with this work. 36345035 5 37 theme RNA-binding 1099:1109 arg1 RBP 1120:1122 RBP 1120:1122 RBP 1120:1122 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 5 37 theme RNA-binding 1099:1109 arg1 protein 1111:1117 RNA-binding protein 1099:1117 RNA-binding protein (RBP) to target transcript interactions using a Global test approach 1099:1186 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 1 38 from increase 125:132 arg1 number 141:146 the number 137:146 the number of RNA-seq datasets investigating heart failure (HF) 137:199 BACKGROUND Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. 36345035 14 39 theme heart 2667:2671 arg1 failure 2673:2679 heart failure 2667:2679 heart failure 2667:2679 We hope that our application will help users to uncover the molecular basis of heart failure. 36345035 11 40 theme CPEB1 2059:2063 arg1 examples 2047:2054 the examples 2043:2054 the examples of CPEB1, which is differentially expressed in the DCMvsHCM contrast 2043:2123 Moreover, we reconstruct RBP - target interaction networks and showcase the examples of CPEB1, which is differentially expressed in the DCMvsHCM contrast. 36345035 8 41 theme predicted 1476:1484 arg1 activity 1486:1493 the predicted activity 1472:1493 the predicted activity for these two kinases 1472:1515 Interestingly, the signs of the predicted activity for these two kinases have been inferred to be opposite to each other: In the DCMvsHCM contrast, we predict ERK1 to be consistently less activated in DCM while ERK2 was more activated in DCM. 36345035 3 42 from patients 589:596 arg1 datasets 539:546 available datasets 529:546 available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy 529:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 42 from patients 589:596 arg1 NFD 696:698 NFD 696:698 NFD 696:698 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 42 from patients 589:596 arg1 hearts 688:693 unmatched non-failing hearts 666:693 unmatched non-failing hearts (NFD) 666:699 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 42 from patients 589:596 arg1 samples 576:582 left ventricular RNA-seq samples 551:582 left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy 551:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 43 theme Applied 459:465 arg1 dataset 492:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 43 theme Applied 459:465 arg1 one 501:503 one 501:503 one 501:503 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 43 theme Applied 459:465 arg1 largest 512:518 largest 512:518 largest 512:518 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 5 44 theme test 1174:1177 arg1 approach 1179:1186 a Global test approach 1165:1186 a Global test approach 1165:1186 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 0 45 theme web 27:29 arg1 application 31:41 an interactive web application 12:41 Magnetique: an interactive web application to explore transcriptome signatures of heart failure. 0:95 Magnetique: an interactive web application to explore transcriptome signatures of heart failure. 36345035 5 46 theme target 1128:1133 arg1 interactions 1146:1157 target transcript interactions 1128:1157 target transcript interactions using a Global test approach 1128:1186 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 3 47 dep METHODS 422:428 arg1 reanalysed 433:442 reanalysed 433:442 reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors 433:790 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 4 48 theme differential 804:815 arg1 signatures 853:862 differential gene expression, associated pathway signatures 804:862 signatures 853:862 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 2 49 theme web 331:333 arg1 application 335:345 an intuitive and interactive web application 302:345 an intuitive and interactive web application 302:345 We address the need for an intuitive and interactive web application to explore the transcriptional signatures of heart failure with this work. 36345035 13 50 theme web 2492:2494 arg1 application 2496:2506 the web application 2488:2506 the web application ( https://github.com/AnnekathrinSilvia/magnetique ) 2488:2558 The source code for both the analyses ( https://github.com/dieterich-lab/magnetiqueCode2022 ) and the web application ( https://github.com/AnnekathrinSilvia/magnetique ) is available to the public. 36345035 5 51 theme differential 1031:1042 arg1 changes 1079:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 9 52 theme used 1743:1746 arg1 transcripts 1748:1758 149 differently used transcripts 1727:1758 149 differently used transcripts 1727:1758 In the DCMvsHCM contrast, we identified 149 differently used transcripts. 36345035 10 53 theme top 1772:1774 arg1 candidates 1776:1785 the top candidates 1768:1785 the top candidates 1768:1785 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 3 54 theme Network 476:482 arg1 dataset 492:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 54 theme Network 476:482 arg1 one 501:503 one 501:503 one 501:503 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 54 theme Network 476:482 arg1 largest 512:518 largest 512:518 largest 512:518 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 55 theme Myocardial 448:457 arg1 dataset 492:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 55 theme Myocardial 448:457 arg1 one 501:503 one 501:503 one 501:503 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 55 theme Myocardial 448:457 arg1 largest 512:518 largest 512:518 largest 512:518 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 8 56 theme DCMvsHCM 1573:1580 arg1 contrast 1582:1589 the DCMvsHCM contrast 1569:1589 the DCMvsHCM contrast 1569:1589 Interestingly, the signs of the predicted activity for these two kinases have been inferred to be opposite to each other: In the DCMvsHCM contrast, we predict ERK1 to be consistently less activated in DCM while ERK2 was more activated in DCM. 36345035 12 57 dep application 2218:2228 arg1 include 2317:2323 include 2317:2323 to include transcription factor signaling and RBP:RNA interaction networks 2314:2387 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 12 57 dep application 2218:2228 arg1 provide 2233:2239 provide 2233:2239 to provide an interactive view of the HF transcriptome at the RNA isoform level 2230:2308 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 2 58 with signatures 378:387 arg1 work 416:419 this work 411:419 this work 411:419 We address the need for an intuitive and interactive web application to explore the transcriptional signatures of heart failure with this work. 36345035 5 59 theme first 1016:1020 arg1 time 1022:1025 the first time 1012:1025 the first time 1012:1025 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 12 60 theme isoform 2296:2302 arg1 level 2304:2308 the RNA isoform level 2288:2308 the RNA isoform level 2288:2308 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 10 61 theme O-linked 1794:1801 arg1 GlcNAc 1824:1829 GlcNAc 1824:1829 GlcNAc 1824:1829 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 10 61 theme O-linked 1794:1801 arg1 N-acetylglucosamine 1803:1821 O-linked N-acetylglucosamine 1794:1821 the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 1790:1848 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 1 62 theme critical 237:244 arg1 issues 246:251 critical issues 237:251 critical issues for medical researchers 237:275 BACKGROUND Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. 36345035 4 63 theme pathway 845:851 arg1 signatures 853:862 differential gene expression, associated pathway signatures 804:862 signatures 853:862 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 3 64 theme unmatched 666:674 arg1 NFD 696:698 NFD 696:698 NFD 696:698 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 64 theme unmatched 666:674 arg1 hearts 688:693 unmatched non-failing hearts 666:693 unmatched non-failing hearts (NFD) 666:699 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 12 65 theme transcriptome 2271:2283 arg1 view 2256:2259 an interactive view 2241:2259 an interactive view of the HF transcriptome 2241:2283 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 1 66 theme datasets 159:166 arg1 number 141:146 the number 137:146 the number of RNA-seq datasets investigating heart failure (HF) 137:199 BACKGROUND Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. 36345035 4 67 theme gene 817:820 arg1 signatures 853:862 differential gene expression, associated pathway signatures 804:862 signatures 853:862 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 3 68 theme RNA-seq 568:574 arg1 samples 576:582 left ventricular RNA-seq samples 551:582 left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy 551:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 1 69 theme heart 182:186 arg1 HF 197:198 HF 197:198 HF 197:198 BACKGROUND Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. 36345035 1 69 theme heart 182:186 arg1 failure 188:194 heart failure 182:194 heart failure (HF) 182:199 BACKGROUND Despite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. 36345035 12 70 theme RNA 2364:2366 arg1 networks 2380:2387 transcription factor signaling and RBP:RNA interaction networks 2325:2387 networks 2380:2387 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 3 71 theme patient 723:729 arg1 characteristics 731:745 patient characteristics 723:745 patient characteristics 723:745 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 72 theme left 551:554 arg1 samples 576:582 left ventricular RNA-seq samples 551:582 left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy 551:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 7 73 from changes 1408:1414 arg1 signaling 1433:1441 ERK1 and ERK2 signaling 1419:1441 ERK1 and ERK2 signaling 1419:1441 RESULTS Focusing on the DCM versus HCM contrast (DCMvsHCM), we identified 201 differentially expressed genes, some of which can be clearly associated with changes in ERK1 and ERK2 signaling. 36345035 4 74 theme inferred 908:915 arg1 activities 938:947 inferred transcription factor activities 908:947 inferred transcription factor activities 908:947 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 12 75 theme interactive 2244:2254 arg1 view 2256:2259 an interactive view 2241:2259 an interactive view of the HF transcriptome 2241:2283 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 5 76 theme DTU 1074:1076 arg1 changes 1079:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 4 77 theme factor 931:936 arg1 activities 938:947 inferred transcription factor activities 908:947 inferred transcription factor activities 908:947 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 6 78 theme pairwise 1215:1222 arg1 comparisons 1224:1234 all pairwise comparisons 1211:1234 all pairwise comparisons (DCM, HCM, NFD) 1211:1250 We report results for all pairwise comparisons (DCM, HCM, NFD). 36345035 4 79 theme signaling 880:888 arg1 networks 890:897 signaling networks 880:897 signaling networks based on inferred transcription factor activities 880:947 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 5 80 theme transcript 1048:1057 arg1 changes 1079:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 3 81 dep datasets 539:546 arg1 donors 712:717 organ donors 706:717 organ donors 706:717 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 81 dep datasets 539:546 arg1 characteristics 731:745 patient characteristics 723:745 patient characteristics 723:745 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 5 82 theme usage 1067:1071 arg1 changes 1079:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 differential RNA transcript isoform usage (DTU) changes 1031:1085 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 12 83 dep Magnetique 2137:2146 arg1 https 2150:2154 https 2150:2154 https://shiny.dieterichlab.org/app/magnetique 2150:2194 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 3 84 theme RNA-seq 484:490 arg1 dataset 492:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 84 theme RNA-seq 484:490 arg1 one 501:503 one 501:503 one 501:503 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 84 theme RNA-seq 484:490 arg1 largest 512:518 largest 512:518 largest 512:518 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 11 85 theme DCMvsHCM 2107:2114 arg1 contrast 2116:2123 the DCMvsHCM contrast 2103:2123 the DCMvsHCM contrast 2103:2123 Moreover, we reconstruct RBP - target interaction networks and showcase the examples of CPEB1, which is differentially expressed in the DCMvsHCM contrast. 36345035 3 86 with patients 589:596 arg1 DCM 612:614 DCM 612:614 DCM 612:614 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 86 with patients 589:596 arg1 dilated 603:609 dilated 603:609 dilated 603:609 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 86 with patients 589:596 arg1 cardiomyopathy 639:652 dilated (DCM) or hypertrophic (HCM) cardiomyopathy 603:652 cardiomyopathy 639:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 0 87 theme heart 82:86 arg1 failure 88:94 heart failure 82:94 heart failure 82:94 Magnetique: an interactive web application to explore transcriptome signatures of heart failure. 36345035 12 88 theme first 2205:2209 arg1 application 2218:2228 the first online application 2201:2228 the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks 2201:2387 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 12 88 theme first 2205:2209 arg1 Magnetique 2137:2146 CONCLUSION Magnetique 2126:2146 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) 2126:2196 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 3 89 from datasets 539:546 arg1 patients 589:596 patients 589:596 patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy 589:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 2 90 theme intuitive 305:313 arg1 application 335:345 an intuitive and interactive web application 302:345 an intuitive and interactive web application 302:345 We address the need for an intuitive and interactive web application to explore the transcriptional signatures of heart failure with this work. 36345035 7 91 theme HCM 1288:1290 arg1 contrast 1292:1299 HCM contrast 1288:1299 HCM contrast 1288:1299 RESULTS Focusing on the DCM versus HCM contrast (DCMvsHCM), we identified 201 differentially expressed genes, some of which can be clearly associated with changes in ERK1 and ERK2 signaling. 36345035 4 92 theme linear 965:970 arg1 programming 972:982 integer linear programming 957:982 integer linear programming 957:982 We analyse differential gene expression, associated pathway signatures and reconstruct signaling networks based on inferred transcription factor activities through integer linear programming. 36345035 12 93 theme CONCLUSION 2126:2135 arg1 application 2218:2228 the first online application 2201:2228 the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks 2201:2387 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 12 93 theme CONCLUSION 2126:2135 arg1 Magnetique 2137:2146 CONCLUSION Magnetique 2126:2146 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) 2126:2196 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 9 94 theme DCMvsHCM 1694:1701 arg1 contrast 1703:1710 the DCMvsHCM contrast 1690:1710 the DCMvsHCM contrast 1690:1710 In the DCMvsHCM contrast, we identified 149 differently used transcripts. 36345035 8 95 theme activity 1486:1493 arg1 signs 1463:1467 the signs 1459:1467 the signs of the predicted activity for these two kinases 1459:1515 Interestingly, the signs of the predicted activity for these two kinases have been inferred to be opposite to each other: In the DCMvsHCM contrast, we predict ERK1 to be consistently less activated in DCM while ERK2 was more activated in DCM. 36345035 8 95 theme activity 1486:1493 arg1 opposite 1542:1549 opposite 1542:1549 opposite 1542:1549 Interestingly, the signs of the predicted activity for these two kinases have been inferred to be opposite to each other: In the DCMvsHCM contrast, we predict ERK1 to be consistently less activated in DCM while ERK2 was more activated in DCM. 36345035 2 96 theme transcriptional 362:376 arg1 signatures 378:387 the transcriptional signatures 358:387 the transcriptional signatures of heart failure with this work 358:419 We address the need for an intuitive and interactive web application to explore the transcriptional signatures of heart failure with this work. 36345035 0 97 theme interactive 15:25 arg1 application 31:41 an interactive web application 12:41 Magnetique: an interactive web application to explore transcriptome signatures of heart failure. 0:95 Magnetique: an interactive web application to explore transcriptome signatures of heart failure. 36345035 5 98 theme Global 1167:1172 arg1 approach 1179:1186 a Global test approach 1165:1186 a Global test approach 1165:1186 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 14 99 theme molecular 2648:2656 arg1 basis 2658:2662 the molecular basis 2644:2662 the molecular basis of heart failure 2644:2679 We hope that our application will help users to uncover the molecular basis of heart failure. 36345035 13 100 dep https 2430:2434 arg1 //github.com/dieterich-lab/magnetiqueCode2022 2436:2480 //github.com/dieterich-lab/magnetiqueCode2022 2436:2480 //github.com/dieterich-lab/magnetiqueCode2022 2436:2480 The source code for both the analyses ( https://github.com/dieterich-lab/magnetiqueCode2022 ) and the web application ( https://github.com/AnnekathrinSilvia/magnetique ) is available to the public. 36345035 12 101 theme RBP 2360:2362 arg1 networks 2380:2387 transcription factor signaling and RBP:RNA interaction networks 2325:2387 networks 2380:2387 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 3 102 theme HCM 634:636 arg1 cardiomyopathy 639:652 dilated (DCM) or hypertrophic (HCM) cardiomyopathy 603:652 cardiomyopathy 639:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 103 theme Genomics 467:474 arg1 dataset 492:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 103 theme Genomics 467:474 arg1 one 501:503 one 501:503 one 501:503 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 103 theme Genomics 467:474 arg1 largest 512:518 largest 512:518 largest 512:518 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 7 104 dep DCM 1277:1279 arg1 the 1273:1275 the 1273:1275 the 1273:1275 RESULTS Focusing on the DCM versus HCM contrast (DCMvsHCM), we identified 201 differentially expressed genes, some of which can be clearly associated with changes in ERK1 and ERK2 signaling. 36345035 13 105 dep analyses 2419:2426 arg1 https 2430:2434 https 2430:2434 https://github.com/dieterich-lab/magnetiqueCode2022 2430:2480 The source code for both the analyses ( https://github.com/dieterich-lab/magnetiqueCode2022 ) and the web application ( https://github.com/AnnekathrinSilvia/magnetique ) is available to the public. 36345035 3 106 theme hypertrophic 620:631 arg1 cardiomyopathy 639:652 dilated (DCM) or hypertrophic (HCM) cardiomyopathy 603:652 cardiomyopathy 639:652 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 2 107 theme failure 398:404 arg1 signatures 378:387 the transcriptional signatures 358:387 the transcriptional signatures of heart failure with this work 358:419 We address the need for an intuitive and interactive web application to explore the transcriptional signatures of heart failure with this work. 36345035 5 108 theme transcript 1135:1144 arg1 interactions 1146:1157 target transcript interactions 1128:1157 target transcript interactions using a Global test approach 1128:1186 We additionally focus, for the first time, on differential RNA transcript isoform usage (DTU) changes and predict RNA-binding protein (RBP) to target transcript interactions using a Global test approach. 36345035 10 109 from role 1922:1925 arg1 arrhythmias 1936:1946 heart arrhythmias 1930:1946 heart arrhythmias 1930:1946 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 10 109 from role 1922:1925 arg1 hypertrophy 1958:1968 heart hypertrophy 1952:1968 heart hypertrophy 1952:1968 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 0 110 dep application 31:41 arg1 explore 46:52 explore 46:52 to explore transcriptome signatures of heart failure 43:94 Magnetique: an interactive web application to explore transcriptome signatures of heart failure. 36345035 12 111 theme transcription 2325:2337 arg1 signaling 2346:2354 transcription factor signaling and RBP:RNA interaction networks 2325:2387 signaling 2346:2354 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 3 112 theme non-failing 676:686 arg1 NFD 696:698 NFD 696:698 NFD 696:698 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 112 theme non-failing 676:686 arg1 hearts 688:693 unmatched non-failing hearts 666:693 unmatched non-failing hearts (NFD) 666:699 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 10 113 theme candidates 1776:1785 arg1 One 1761:1763 One 1761:1763 One 1761:1763 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 10 113 theme candidates 1776:1785 arg1 transferase 1832:1842 the O-linked N-acetylglucosamine (GlcNAc) transferase 1790:1842 the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 1790:1848 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 10 113 theme candidates 1776:1785 arg1 candidates 1776:1785 the top candidates 1768:1785 the top candidates 1768:1785 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 2 114 theme interactive 319:329 arg1 application 335:345 an intuitive and interactive web application 302:345 an intuitive and interactive web application 302:345 We address the need for an intuitive and interactive web application to explore the transcriptional signatures of heart failure with this work. 36345035 0 115 dep Magnetique 0:9 arg1 application 31:41 an interactive web application 12:41 Magnetique: an interactive web application to explore transcriptome signatures of heart failure. 0:95 Magnetique: an interactive web application to explore transcriptome signatures of heart failure. 36345035 10 116 theme heart 1952:1956 arg1 hypertrophy 1958:1968 heart hypertrophy 1952:1968 heart hypertrophy 1952:1968 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 12 117 theme RNA 2292:2294 arg1 level 2304:2308 the RNA isoform level 2288:2308 the RNA isoform level 2288:2308 CONCLUSION Magnetique ( https://shiny.dieterichlab.org/app/magnetique ) is the first online application to provide an interactive view of the HF transcriptome at the RNA isoform level and to include transcription factor signaling and RBP:RNA interaction networks. 36345035 10 118 link O-linked 1794:1801 arg1 GlcNAc 1824:1829 GlcNAc 1824:1829 GlcNAc 1824:1829 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 10 118 link O-linked 1794:1801 arg1 N-acetylglucosamine 1803:1821 O-linked N-acetylglucosamine 1794:1821 the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 1790:1848 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 10 119 theme N-acetylglucosamine 1803:1821 arg1 One 1761:1763 One 1761:1763 One 1761:1763 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 10 119 theme N-acetylglucosamine 1803:1821 arg1 OGT 1845:1847 OGT 1845:1847 OGT 1845:1847 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 10 119 theme N-acetylglucosamine 1803:1821 arg1 candidates 1776:1785 the top candidates 1768:1785 the top candidates 1768:1785 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 10 119 theme N-acetylglucosamine 1803:1821 arg1 transferase 1832:1842 the O-linked N-acetylglucosamine (GlcNAc) transferase 1790:1842 the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) 1790:1848 One of the top candidates is the O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which catalyzes a common post-translational modification known for its role in heart arrhythmias and heart hypertrophy. 36345035 3 120 theme largest 512:518 arg1 dataset 492:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 the Myocardial Applied Genomics Network RNA-seq dataset 444:498 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 120 theme largest 512:518 arg1 one 501:503 one 501:503 one 501:503 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 36345035 3 120 theme largest 512:518 arg1 largest 512:518 largest 512:518 largest 512:518 METHODS We reanalysed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts (NFD) from organ donors and patient characteristics that allowed us to model confounding factors. 33084982 0 0 theme non-alcoholic 92:104 arg1 disease 118:124 non-alcoholic fatty liver disease 92:124 non-alcoholic fatty liver disease 92:124 Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease. 33084982 6 1 from plasma 896:901 arg1 N-acyl 862:867 N-acyl 862:867 N-acyl 862:867 METHODS Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. 33084982 5 2 theme deoxy 645:649 arg1 sphingolipids 651:663 circulating (deoxy)sphingolipids 632:663 circulating (deoxy)sphingolipids 632:663 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 9 3 theme steatosis 1185:1193 arg1 presence 1173:1180 the presence 1169:1180 the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 1169:1252 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 2 4 dep inflammation 287:298 arg1 NASH 348:351 NASH 348:351 NASH 348:351 Steatosis can be accompanied by inflammation and cell damage (non-alcoholic steatohepatitis, NASH), and even liver fibrosis. 33084982 2 4 dep inflammation 287:298 arg1 fibrosis 370:377 liver fibrosis 364:377 liver fibrosis 364:377 Steatosis can be accompanied by inflammation and cell damage (non-alcoholic steatohepatitis, NASH), and even liver fibrosis. 33084982 2 4 dep inflammation 287:298 arg1 steatohepatitis 331:345 non-alcoholic steatohepatitis 317:345 non-alcoholic steatohepatitis 317:345 Steatosis can be accompanied by inflammation and cell damage (non-alcoholic steatohepatitis, NASH), and even liver fibrosis. 33084982 9 5 with association 1149:1159 arg1 CI 1259:1260 CI 1259:1260 CI 1259:1260 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 11 6 theme diabetes 1628:1635 arg1 presence 1584:1591 the presence 1580:1591 the presence of the metabolic syndrome, but not diabetes 1580:1635 Differences in deoxy-sphingolipids also correlated independently with the presence of the metabolic syndrome, but not diabetes. 33084982 6 7 theme adults 912:917 arg1 plasma 896:901 plasma 896:901 plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD 896:968 METHODS Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. 33084982 12 8 theme further 1896:1902 arg1 progression 1904:1914 the further progression 1892:1914 the further progression of NAFLD to NASH 1892:1931 CONCLUSION Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis. 33084982 11 9 from Differences 1510:1520 arg1 deoxy-sphingolipids 1525:1543 deoxy-sphingolipids 1525:1543 deoxy-sphingolipids 1525:1543 Differences in deoxy-sphingolipids also correlated independently with the presence of the metabolic syndrome, but not diabetes. 33084982 10 10 with association 1483:1493 arg1 fibrosis 1500:1507 fibrosis 1500:1507 fibrosis 1500:1507 There was no association between these deoxy-sphingolipids and activity of the steatohepatitis, nor was there any association with fibrosis. 33084982 9 11 dep 36.306 1270:1275 arg1 3.437 1338:1342 3.437 1338:1342 3.437 1338:1342 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 0 12 theme liver 112:116 arg1 disease 118:124 non-alcoholic fatty liver disease 92:124 non-alcoholic fatty liver disease 92:124 Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease. 33084982 4 13 theme atypical 507:514 arg1 class 516:520 The atypical class 503:520 The atypical class of deoxy-sphingolipids 503:543 The atypical class of deoxy-sphingolipids has been implicated in the metabolic syndrome and type 2 diabetes. 33084982 12 14 theme NAFLD 1788:1792 arg1 subtypes 1794:1801 the different NAFLD subtypes 1774:1801 the different NAFLD subtypes 1774:1801 CONCLUSION Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis. 33084982 0 15 theme fatty 106:110 arg1 disease 118:124 non-alcoholic fatty liver disease 92:124 non-alcoholic fatty liver disease 92:124 Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease. 33084982 12 16 theme NAFLD 1919:1923 arg1 progression 1904:1914 the further progression 1892:1914 the further progression of NAFLD to NASH 1892:1931 CONCLUSION Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis. 33084982 9 17 theme concentrations 1203:1216 arg1 presence 1173:1180 the presence 1169:1180 the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 1169:1252 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 12 18 theme CONCLUSION 1638:1647 arg1 Deoxy-sphingolipids 1649:1667 CONCLUSION Deoxy-sphingolipids 1638:1667 CONCLUSION Deoxy-sphingolipids 1638:1667 CONCLUSION Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis. 33084982 2 19 theme non-alcoholic 317:329 arg1 NASH 348:351 NASH 348:351 NASH 348:351 Steatosis can be accompanied by inflammation and cell damage (non-alcoholic steatohepatitis, NASH), and even liver fibrosis. 33084982 2 19 theme non-alcoholic 317:329 arg1 steatohepatitis 331:345 non-alcoholic steatohepatitis 317:345 non-alcoholic steatohepatitis 317:345 Steatosis can be accompanied by inflammation and cell damage (non-alcoholic steatohepatitis, NASH), and even liver fibrosis. 33084982 5 20 theme inflammatory 730:741 arg1 inflammation 752:763 inflammation 752:763 inflammation 752:763 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 5 20 theme inflammatory 730:741 arg1 changes 743:749 inflammatory changes 730:749 inflammatory changes (inflammation and ballooning) 730:779 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 5 20 theme inflammatory 730:741 arg1 entities 709:716 its different entities 695:716 its different entities 695:716 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 5 20 theme inflammatory 730:741 arg1 ballooning 769:778 ballooning 769:778 ballooning 769:778 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 3 21 theme plasma 482:487 arg1 lipoproteins 489:500 the plasma membrane and plasma lipoproteins 458:500 lipoproteins 489:500 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 8 22 theme typical 1065:1071 arg1 sphingolipids 1073:1085 typical sphingolipids 1065:1085 typical sphingolipids 1065:1085 There was no association between typical sphingolipids and NAFLD and its different entities. 33084982 6 23 theme METHODS 795:801 arg1 Sphingolipids 803:815 METHODS Sphingolipids 795:815 METHODS Sphingolipids 795:815 METHODS Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. 33084982 4 24 theme type 595:598 arg1 diabetes 602:609 type 2 diabetes 595:609 type 2 diabetes 595:609 The atypical class of deoxy-sphingolipids has been implicated in the metabolic syndrome and type 2 diabetes. 33084982 9 25 theme [exp 1315:1318 arg1 B 1320:1320 deoxy-sphingosine [exp(B) 8.486 1297:1327 deoxy-sphingosine [exp(B) 8.486 with CI 1297:1335 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 3 26 theme lipids 423:428 arg1 Sphingolipids 380:392 Sphingolipids 380:392 Sphingolipids 380:392 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 3 26 theme lipids 423:428 arg1 components 444:453 essential components 434:453 essential components of the plasma membrane and plasma lipoproteins 434:500 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 3 26 theme lipids 423:428 arg1 class 414:418 a heterogeneous class 398:418 a heterogeneous class of lipids 398:428 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 9 27 theme deoxy-sphinganine 1221:1237 arg1 11.163 1247:1252 deoxy-sphinganine [exp(B) 11.163 1221:1252 deoxy-sphinganine [exp(B) 11.163 1221:1252 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 10 28 dep deoxy-sphingolipids 1408:1426 arg1 these 1402:1406 these 1402:1406 these 1402:1406 There was no association between these deoxy-sphingolipids and activity of the steatohepatitis, nor was there any association with fibrosis. 33084982 3 29 theme essential 434:442 arg1 components 444:453 essential components 434:453 essential components of the plasma membrane and plasma lipoproteins 434:500 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 6 30 from N-acyl 862:867 arg1 plasma 896:901 plasma 896:901 plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD 896:968 METHODS Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. 33084982 0 31 from steatosis 42:50 arg1 disease 118:124 non-alcoholic fatty liver disease 92:124 non-alcoholic fatty liver disease 92:124 Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease. 33084982 5 32 theme circulating 632:642 arg1 sphingolipids 651:663 circulating (deoxy)sphingolipids 632:663 circulating (deoxy)sphingolipids 632:663 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 9 33 theme [exp 1239:1242 arg1 11.163 1247:1252 deoxy-sphinganine [exp(B) 11.163 1221:1252 deoxy-sphinganine [exp(B) 11.163 1221:1252 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 9 34 theme deoxy-sphingosine 1297:1313 arg1 B 1320:1320 deoxy-sphingosine [exp(B) 8.486 1297:1327 deoxy-sphingosine [exp(B) 8.486 with CI 1297:1335 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 10 35 theme steatohepatitis 1448:1462 arg1 activity 1432:1439 activity 1432:1439 activity 1432:1439 There was no association between these deoxy-sphingolipids and activity of the steatohepatitis, nor was there any association with fibrosis. 33084982 10 35 theme steatohepatitis 1448:1462 arg1 deoxy-sphingolipids 1408:1426 deoxy-sphingolipids 1408:1426 deoxy-sphingolipids 1408:1426 There was no association between these deoxy-sphingolipids and activity of the steatohepatitis, nor was there any association with fibrosis. 33084982 12 36 theme deoxy-sphingolipid 1820:1837 arg1 bases 1839:1843 deoxy-sphingolipid bases 1820:1843 deoxy-sphingolipid bases 1820:1843 CONCLUSION Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis. 33084982 9 37 with B 1320:1320 arg1 CI 1334:1335 CI 1334:1335 CI 1334:1335 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 12 38 with patients 1685:1692 arg1 steatosis 1699:1707 steatosis 1699:1707 steatosis compared to those without fatty liver 1699:1745 CONCLUSION Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis. 33084982 2 39 theme liver 364:368 arg1 fibrosis 370:377 liver fibrosis 364:377 liver fibrosis 364:377 Steatosis can be accompanied by inflammation and cell damage (non-alcoholic steatohepatitis, NASH), and even liver fibrosis. 33084982 6 40 theme NAFLD 964:968 arg1 suspicion 951:959 suspicion 951:959 suspicion of NAFLD 951:968 METHODS Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. 33084982 9 41 theme B 1244:1244 arg1 11.163 1247:1252 deoxy-sphinganine [exp(B) 11.163 1221:1252 deoxy-sphinganine [exp(B) 11.163 1221:1252 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 2 42 theme cell 304:307 arg1 damage 309:314 cell damage 304:314 cell damage 304:314 Steatosis can be accompanied by inflammation and cell damage (non-alcoholic steatohepatitis, NASH), and even liver fibrosis. 33084982 7 43 dep Two-hundred 979:989 arg1 RESULTS 971:977 RESULTS 971:977 RESULTS 971:977 RESULTS Two-hundred and eighty-eight patients were included. 33084982 7 43 dep Two-hundred 979:989 arg1 patients 1008:1015 patients 1008:1015 patients 1008:1015 RESULTS Two-hundred and eighty-eight patients were included. 33084982 0 44 theme 1-deoxy-sphingolipids 15:35 arg1 Association 0:10 Association 0:10 Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease. 0:125 Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease. 33084982 4 45 theme metabolic 572:580 arg1 syndrome 582:589 the metabolic syndrome 568:589 the metabolic syndrome 568:589 The atypical class of deoxy-sphingolipids has been implicated in the metabolic syndrome and type 2 diabetes. 33084982 5 46 theme different 699:707 arg1 fibrosis 785:792 fibrosis 785:792 fibrosis 785:792 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 5 46 theme different 699:707 arg1 steatosis 719:727 steatosis 719:727 steatosis 719:727 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 5 46 theme different 699:707 arg1 changes 743:749 inflammatory changes 730:749 inflammatory changes (inflammation and ballooning) 730:779 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 5 46 theme different 699:707 arg1 entities 709:716 its different entities 695:716 its different entities 695:716 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 3 47 theme plasma 462:467 arg1 membrane 469:476 the plasma membrane and plasma lipoproteins 458:500 membrane 469:476 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 3 48 theme heterogeneous 400:412 arg1 Sphingolipids 380:392 Sphingolipids 380:392 Sphingolipids 380:392 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 3 48 theme heterogeneous 400:412 arg1 class 414:418 a heterogeneous class 398:418 a heterogeneous class of lipids 398:428 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 3 49 theme lipoproteins 489:500 arg1 Sphingolipids 380:392 Sphingolipids 380:392 Sphingolipids 380:392 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 3 49 theme lipoproteins 489:500 arg1 components 444:453 essential components 434:453 essential components of the plasma membrane and plasma lipoproteins 434:500 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 3 49 theme lipoproteins 489:500 arg1 class 414:418 a heterogeneous class 398:418 a heterogeneous class of lipids 398:428 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 8 50 theme different 1105:1113 arg1 entities 1115:1122 its different entities 1101:1122 its different entities 1101:1122 There was no association between typical sphingolipids and NAFLD and its different entities. 33084982 9 51 theme 11.163 1247:1252 arg1 concentrations 1203:1216 the concentrations 1199:1216 the concentrations of deoxy-sphinganine [exp(B) 11.163 1199:1252 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 9 51 theme 11.163 1247:1252 arg1 steatosis 1185:1193 steatosis 1185:1193 steatosis 1185:1193 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 1 52 theme important 192:200 arg1 disease 164:170 BACKGROUND Non-alcoholic fatty liver disease 127:170 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) 127:178 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 52 theme important 192:200 arg1 cause 202:206 the most important cause 183:206 the most important cause of chronic liver disease in the western world 183:252 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 53 theme chronic 211:217 arg1 disease 225:231 chronic liver disease 211:231 chronic liver disease 211:231 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 4 54 theme deoxy-sphingolipids 525:543 arg1 class 516:520 The atypical class 503:520 The atypical class of deoxy-sphingolipids 503:543 The atypical class of deoxy-sphingolipids has been implicated in the metabolic syndrome and type 2 diabetes. 33084982 1 55 theme liver 219:223 arg1 disease 225:231 chronic liver disease 211:231 chronic liver disease 211:231 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 6 56 dep N-acyl 862:867 arg1 headgroups 882:891 headgroups 882:891 headgroups 882:891 METHODS Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. 33084982 9 57 theme significant 1137:1147 arg1 association 1149:1159 a significant association 1135:1159 a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI 1135:1260 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 1 58 theme BACKGROUND 127:136 arg1 NAFLD 173:177 NAFLD 173:177 NAFLD 173:177 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 58 theme BACKGROUND 127:136 arg1 cause 202:206 the most important cause 183:206 the most important cause of chronic liver disease in the western world 183:252 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 58 theme BACKGROUND 127:136 arg1 disease 164:170 BACKGROUND Non-alcoholic fatty liver disease 127:170 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) 127:178 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 6 59 theme obese 906:910 arg1 adults 912:917 obese adults 906:917 obese adults who underwent a liver biopsy in suspicion of NAFLD 906:968 METHODS Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. 33084982 6 60 theme liver 935:939 arg1 biopsy 941:946 a liver biopsy 933:946 a liver biopsy 933:946 METHODS Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. 33084982 5 61 dep changes 743:749 arg1 inflammation 752:763 inflammation 752:763 inflammation 752:763 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 5 61 dep changes 743:749 arg1 changes 743:749 inflammatory changes 730:749 inflammatory changes (inflammation and ballooning) 730:779 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 5 61 dep changes 743:749 arg1 ballooning 769:778 ballooning 769:778 ballooning 769:778 AIM To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. 33084982 1 62 from cause 202:206 arg1 world 248:252 the western world 236:252 the western world 236:252 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 63 theme Non-alcoholic 138:150 arg1 NAFLD 173:177 NAFLD 173:177 NAFLD 173:177 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 63 theme Non-alcoholic 138:150 arg1 cause 202:206 the most important cause 183:206 the most important cause of chronic liver disease in the western world 183:252 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 63 theme Non-alcoholic 138:150 arg1 disease 164:170 BACKGROUND Non-alcoholic fatty liver disease 127:170 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) 127:178 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 12 64 theme different 1778:1786 arg1 subtypes 1794:1801 the different NAFLD subtypes 1774:1801 the different NAFLD subtypes 1774:1801 CONCLUSION Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis. 33084982 11 65 theme syndrome 1610:1617 arg1 presence 1584:1591 the presence 1580:1591 the presence of the metabolic syndrome, but not diabetes 1580:1635 Differences in deoxy-sphingolipids also correlated independently with the presence of the metabolic syndrome, but not diabetes. 33084982 12 66 theme fatty 1735:1739 arg1 liver 1741:1745 fatty liver 1735:1745 fatty liver 1735:1745 CONCLUSION Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis. 33084982 0 67 with Association 0:10 arg1 fibrosis 80:87 fibrosis 80:87 fibrosis 80:87 Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease. 33084982 0 67 with Association 0:10 arg1 steatosis 42:50 steatosis 42:50 steatosis 42:50 Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease. 33084982 0 67 with Association 0:10 arg1 steatohepatitis 60:74 steatohepatitis 60:74 steatohepatitis 60:74 Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease. 33084982 1 68 theme fatty 152:156 arg1 NAFLD 173:177 NAFLD 173:177 NAFLD 173:177 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 68 theme fatty 152:156 arg1 cause 202:206 the most important cause 183:206 the most important cause of chronic liver disease in the western world 183:252 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 68 theme fatty 152:156 arg1 disease 164:170 BACKGROUND Non-alcoholic fatty liver disease 127:170 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) 127:178 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 69 theme disease 225:231 arg1 disease 164:170 BACKGROUND Non-alcoholic fatty liver disease 127:170 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) 127:178 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 69 theme disease 225:231 arg1 cause 202:206 the most important cause 183:206 the most important cause of chronic liver disease in the western world 183:252 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 12 70 from patients 1685:1692 arg1 elevated 1673:1680 elevated 1673:1680 elevated 1673:1680 CONCLUSION Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis. 33084982 11 71 theme metabolic 1600:1608 arg1 syndrome 1610:1617 the metabolic syndrome 1596:1617 the metabolic syndrome 1596:1617 Differences in deoxy-sphingolipids also correlated independently with the presence of the metabolic syndrome, but not diabetes. 33084982 1 72 theme liver 158:162 arg1 NAFLD 173:177 NAFLD 173:177 NAFLD 173:177 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 72 theme liver 158:162 arg1 cause 202:206 the most important cause 183:206 the most important cause of chronic liver disease in the western world 183:252 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 1 72 theme liver 158:162 arg1 disease 164:170 BACKGROUND Non-alcoholic fatty liver disease 127:170 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) 127:178 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 33084982 3 73 theme membrane 469:476 arg1 Sphingolipids 380:392 Sphingolipids 380:392 Sphingolipids 380:392 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 3 73 theme membrane 469:476 arg1 components 444:453 essential components 434:453 essential components of the plasma membrane and plasma lipoproteins 434:500 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 3 73 theme membrane 469:476 arg1 class 414:418 a heterogeneous class 398:418 a heterogeneous class of lipids 398:428 Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. 33084982 9 74 dep was 1131:1133 arg1 p < 0.001 1282:1290 p < 0.001 1282:1290 p < 0.001 1282:1290 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 9 74 dep was 1131:1133 arg1 B 1320:1320 deoxy-sphingosine [exp(B) 8.486 1297:1327 deoxy-sphingosine [exp(B) 8.486 with CI 1297:1335 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 9 74 dep was 1131:1133 arg1 p < 0.001 1357:1365 p < 0.001 1357:1365 p < 0.001 1357:1365 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 9 74 dep was 1131:1133 arg1 36.306 1270:1275 36.306 1270:1275 36.306 1270:1275 There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. 33084982 12 75 from elevated 1673:1680 arg1 patients 1685:1692 patients 1685:1692 patients with steatosis compared to those without fatty liver 1685:1745 CONCLUSION Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis. 33084982 1 76 theme western 240:246 arg1 world 248:252 the western world 236:252 the western world 236:252 BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. 37192126 11 0 dep CONCLUSION 1494:1503 arg1 conclude 1508:1515 conclude 1508:1515 conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA 1508:1696 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 2 1 theme untreated 309:317 arg1 n=9 332:334 n=9 332:334 n=9 332:334 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 2 1 theme untreated 309:317 arg1 patients 322:329 early untreated RA patients 303:329 early untreated RA patients (n=9) 303:335 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 9 2 theme variable 1368:1375 arg1 region 1377:1382 the variable region 1364:1382 the variable region 1364:1382 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 8 3 theme memory 1115:1120 arg1 subsets 1129:1135 different memory B cell subsets 1105:1135 different memory B cell subsets where identified 1105:1152 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 6 4 theme increased 833:841 arg1 proportions 843:853 significantly increased proportions 819:853 significantly increased proportions of B lymphocytes 819:870 RESULTS By our single cell approach, we found significantly increased proportions of B lymphocytes in autoantibody-positive as compared to negative individuals. 37192126 7 5 from subgroups 996:1004 arg1 prominent 979:987 prominent 979:987 prominent 979:987 Memory and double negative (DN) B cells were prominent in all subgroups. 37192126 11 6 theme somatic 1599:1605 arg1 hypermutation 1607:1619 somatic hypermutation 1599:1619 somatic hypermutation 1599:1619 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 8 7 theme cell 1124:1127 arg1 subsets 1129:1135 different memory B cell subsets 1105:1135 different memory B cell subsets where identified 1105:1152 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 8 8 theme RA 1181:1182 arg1 patients 1184:1191 at-risk and early RA patients 1163:1191 at-risk and early RA patients 1163:1191 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 2 9 theme lung-resident 236:248 arg1 cells 252:256 lung-resident B cells 236:256 lung-resident B cells 236:256 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 4 10 theme region 596:601 arg1 transcripts 603:613 The Immunoglobulin variable region transcripts 568:613 The Immunoglobulin variable region transcripts 568:613 The Immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n=141). 37192126 4 10 theme region 596:601 arg1 antibodies 672:681 monoclonal antibodies 661:681 monoclonal antibodies (n=141) 661:689 The Immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n=141). 37192126 6 11 theme negative 912:919 arg1 individuals 921:931 negative individuals 912:931 negative individuals 912:931 RESULTS By our single cell approach, we found significantly increased proportions of B lymphocytes in autoantibody-positive as compared to negative individuals. 37192126 2 12 from patients 322:329 arg1 samples 290:296 bronchoalveolar lavage (BAL) samples 261:296 bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3) 261:434 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 2 13 theme bronchoalveolar 261:275 arg1 lavage 277:282 bronchoalveolar lavage 261:282 bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3) 261:434 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 2 13 theme bronchoalveolar 261:275 arg1 BAL 285:287 BAL 285:287 BAL 285:287 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 7 14 theme DN 962:963 arg1 cells 968:972 Memory and double negative (DN) B cells 934:972 cells 968:972 Memory and double negative (DN) B cells were prominent in all subgroups. 37192126 1 15 theme RA 189:190 arg1 onset 167:171 onset 167:171 onset of seropositive RA 167:190 OBJECTIVE The lung is implicated as a site for breaching tolerance prior to onset of seropositive RA. 37192126 9 16 theme Lung 1194:1197 arg1 transcripts 1217:1227 Lung IgG variable gene transcripts 1194:1227 Lung IgG variable gene transcripts from ACPA-positive individuals 1194:1258 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 7 17 theme negative 952:959 arg1 cells 968:972 Memory and double negative (DN) B cells 934:972 cells 968:972 Memory and double negative (DN) B cells were prominent in all subgroups. 37192126 6 18 theme lymphocytes 860:870 arg1 proportions 843:853 significantly increased proportions 819:853 significantly increased proportions of B lymphocytes 819:870 RESULTS By our single cell approach, we found significantly increased proportions of B lymphocytes in autoantibody-positive as compared to negative individuals. 37192126 9 19 theme variable 1203:1210 arg1 transcripts 1217:1227 Lung IgG variable gene transcripts 1194:1227 Lung IgG variable gene transcripts from ACPA-positive individuals 1194:1258 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 3 20 theme risk-RA 533:539 arg1 phase 541:545 the risk-RA phase 529:545 the risk-RA phase 529:545 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 0 21 from specific 21:28 arg1 lung 50:53 the lung 46:53 the lung before and at the onset of disease 46:88 Rheumatoid arthritis specific autoimmunity in the lung before and at the onset of disease. 37192126 10 22 theme lungs 1396:1400 arg1 ACPAs 1402:1406 the lungs ACPAs 1392:1406 the lungs ACPAs 1392:1406 Two of the lungs ACPAs bound to activated neutrophils, one from an at-risk individual and one from early RA. 37192126 11 23 theme ACPA-positive 1681:1693 arg1 RA 1695:1696 ACPA-positive RA 1681:1696 ACPA-positive RA 1681:1696 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 9 24 theme ACPA-positive 1234:1246 arg1 individuals 1248:1258 ACPA-positive individuals 1234:1258 ACPA-positive individuals 1234:1258 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 12 25 theme seropositive 1814:1825 arg1 RA 1827:1828 seropositive RA 1814:1828 seropositive RA 1814:1828 Our findings add to the notion of lung mucosa being a site for initiation of the citrulline autoimmunity preceding seropositive RA. 37192126 2 26 from individuals 393:403 arg1 samples 290:296 bronchoalveolar lavage (BAL) samples 261:296 bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3) 261:434 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 9 27 gly glycosylation 1305:1317 arg2 p<0.001 1326:1332 p<0.001 1326:1332 p<0.001 1326:1332 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 9 27 gly glycosylation 1305:1317 arg2 sites 1319:1323 frequent mutation-induced N-linked Fab glycosylation sites 1266:1323 frequent mutation-induced N-linked Fab glycosylation sites (p<0.001) 1266:1333 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 2 28 from risk 408:411 arg1 individuals 393:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 2 28 from risk 408:411 arg1 n=9 332:334 n=9 332:334 n=9 332:334 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 2 28 from risk 408:411 arg1 patients 322:329 early untreated RA patients 303:329 early untreated RA patients (n=9) 303:335 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 10 29 theme activated 1417:1425 arg1 neutrophils 1427:1437 activated neutrophils 1417:1437 activated neutrophils 1417:1437 Two of the lungs ACPAs bound to activated neutrophils, one from an at-risk individual and one from early RA. 37192126 2 30 theme anti-citrullinated 341:358 arg1 individuals 393:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 9 31 theme mutation-induced 1275:1290 arg1 sites 1319:1323 frequent mutation-induced N-linked Fab glycosylation sites 1266:1323 frequent mutation-induced N-linked Fab glycosylation sites (p<0.001) 1266:1333 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 9 31 theme mutation-induced 1275:1290 arg1 p<0.001 1326:1332 p<0.001 1326:1332 p<0.001 1326:1332 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 0 32 theme Rheumatoid 0:9 arg1 arthritis 11:19 Rheumatoid arthritis 0:19 Rheumatoid arthritis 0:19 Rheumatoid arthritis specific autoimmunity in the lung before and at the onset of disease. 37192126 9 33 theme Fab 1301:1303 arg1 sites 1319:1323 frequent mutation-induced N-linked Fab glycosylation sites 1266:1323 frequent mutation-induced N-linked Fab glycosylation sites (p<0.001) 1266:1333 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 9 33 theme Fab 1301:1303 arg1 p<0.001 1326:1332 p<0.001 1326:1332 p<0.001 1326:1332 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 12 34 theme autoimmunity 1791:1802 arg1 initiation 1762:1771 initiation 1762:1771 initiation of the citrulline autoimmunity preceding seropositive RA 1762:1828 Our findings add to the notion of lung mucosa being a site for initiation of the citrulline autoimmunity preceding seropositive RA. 37192126 2 35 theme -positive 383:391 arg1 individuals 393:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 2 36 theme ACPA 378:381 arg1 individuals 393:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 6 37 dep RESULTS 773:779 arg1 found 813:817 found 813:817 found significantly increased proportions of B lymphocytes in autoantibody-positive as compared to negative individuals 813:931 RESULTS By our single cell approach, we found significantly increased proportions of B lymphocytes in autoantibody-positive as compared to negative individuals. 37192126 9 38 contain carry 1260:1264 arg2 p<0.001 1326:1332 p<0.001 1326:1332 p<0.001 1326:1332 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 9 38 contain carry 1260:1264 arg1 transcripts 1217:1227 Lung IgG variable gene transcripts 1194:1227 Lung IgG variable gene transcripts from ACPA-positive individuals 1194:1258 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 9 38 contain carry 1260:1264 arg3 framework-3 1349:1359 the framework-3 1345:1359 the framework-3 of the variable region 1345:1382 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 9 38 contain carry 1260:1264 arg2 sites 1319:1323 frequent mutation-induced N-linked Fab glycosylation sites 1266:1323 frequent mutation-induced N-linked Fab glycosylation sites (p<0.001) 1266:1333 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 2 39 theme antibody 368:375 arg1 individuals 393:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 4 40 theme Immunoglobulin 572:585 arg1 region 596:601 Immunoglobulin variable region 572:601 The Immunoglobulin variable region transcripts 568:613 The Immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n=141). 37192126 6 41 theme single 788:793 arg1 approach 800:807 our single cell approach 784:807 our single cell approach 784:807 RESULTS By our single cell approach, we found significantly increased proportions of B lymphocytes in autoantibody-positive as compared to negative individuals. 37192126 3 42 theme RA 554:555 arg1 diagnosis 557:565 RA diagnosis 554:565 RA diagnosis 554:565 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 11 43 theme driven 1529:1534 arg1 differentiation 1543:1557 T cell driven B cell differentiation 1522:1557 T cell driven B cell differentiation 1522:1557 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 2 44 theme early 303:307 arg1 n=9 332:334 n=9 332:334 n=9 332:334 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 2 44 theme early 303:307 arg1 patients 322:329 early untreated RA patients 303:329 early untreated RA patients (n=9) 303:335 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 5 45 theme reactivity 725:734 arg1 patterns 736:743 reactivity patterns 725:743 reactivity patterns 725:743 Monoclonal ACPAs were tested for reactivity patterns and binding to neutrophils. 37192126 12 46 theme lung 1733:1736 arg1 mucosa 1738:1743 lung mucosa 1733:1743 lung mucosa being a site for initiation of the citrulline autoimmunity preceding seropositive RA 1733:1828 Our findings add to the notion of lung mucosa being a site for initiation of the citrulline autoimmunity preceding seropositive RA. 37192126 10 47 theme at-risk 1452:1458 arg1 individual 1460:1469 an at-risk individual 1449:1469 an at-risk individual 1449:1469 Two of the lungs ACPAs bound to activated neutrophils, one from an at-risk individual and one from early RA. 37192126 11 48 theme T 1522:1522 arg1 differentiation 1543:1557 T cell driven B cell differentiation 1522:1557 T cell driven B cell differentiation 1522:1557 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 8 49 theme mutated 1049:1055 arg1 clones 1081:1086 seven highly mutated citrulline autoreactive clones 1036:1086 seven highly mutated citrulline autoreactive clones 1036:1086 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 3 50 theme B 452:452 arg1 n=7680 461:466 n=7680 461:466 n=7680 461:466 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 3 50 theme B 452:452 arg1 cells 454:458 Single B cells 445:458 METHODS Single B cells (n=7680) 437:467 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 8 51 theme autoreactive 1068:1079 arg1 clones 1081:1086 seven highly mutated citrulline autoreactive clones 1036:1086 seven highly mutated citrulline autoreactive clones 1036:1086 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 6 52 theme B 858:858 arg1 lymphocytes 860:870 B lymphocytes 858:870 B lymphocytes 858:870 RESULTS By our single cell approach, we found significantly increased proportions of B lymphocytes in autoantibody-positive as compared to negative individuals. 37192126 7 53 from prominent 979:987 arg1 subgroups 996:1004 all subgroups 992:1004 all subgroups 992:1004 Memory and double negative (DN) B cells were prominent in all subgroups. 37192126 11 54 theme class 1579:1583 arg1 switching 1585:1593 local class switching 1573:1593 local class switching 1573:1593 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 11 55 theme cell 1538:1541 arg1 differentiation 1543:1557 T cell driven B cell differentiation 1522:1557 T cell driven B cell differentiation 1522:1557 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 2 56 theme RA 319:320 arg1 n=9 332:334 n=9 332:334 n=9 332:334 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 2 56 theme RA 319:320 arg1 patients 322:329 early untreated RA patients 303:329 early untreated RA patients (n=9) 303:335 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 9 57 theme region 1377:1382 arg1 framework-3 1349:1359 the framework-3 1345:1359 the framework-3 of the variable region 1345:1382 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 8 58 theme different 1105:1113 arg1 subsets 1129:1135 different memory B cell subsets 1105:1135 different memory B cell subsets where identified 1105:1152 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 3 59 from diagnosis 557:565 arg1 individuals 510:520 individuals 510:520 individuals during the risk-RA phase and at RA diagnosis 510:565 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 3 59 from diagnosis 557:565 arg1 BAL 503:505 BAL 503:505 BAL of individuals during the risk-RA phase and at RA diagnosis 503:565 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 2 60 theme B 250:250 arg1 cells 252:256 lung-resident B cells 236:256 lung-resident B cells 236:256 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 8 61 theme B 1122:1122 arg1 subsets 1129:1135 different memory B cell subsets 1105:1135 different memory B cell subsets where identified 1105:1152 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 8 62 theme early 1175:1179 arg1 patients 1184:1191 at-risk and early RA patients 1163:1191 at-risk and early RA patients 1163:1191 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 4 63 theme variable 587:594 arg1 region 596:601 Immunoglobulin variable region 572:601 The Immunoglobulin variable region transcripts 568:613 The Immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n=141). 37192126 2 64 theme lavage 277:282 arg1 samples 290:296 bronchoalveolar lavage (BAL) samples 261:296 bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3) 261:434 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 3 65 theme individuals 510:520 arg1 BAL 503:505 BAL 503:505 BAL of individuals during the risk-RA phase and at RA diagnosis 503:565 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 1 66 theme seropositive 176:187 arg1 RA 189:190 seropositive RA 176:190 seropositive RA 176:190 OBJECTIVE The lung is implicated as a site for breaching tolerance prior to onset of seropositive RA. 37192126 9 67 from individuals 1248:1258 arg1 transcripts 1217:1227 Lung IgG variable gene transcripts 1194:1227 Lung IgG variable gene transcripts from ACPA-positive individuals 1194:1258 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 8 68 theme at-risk 1163:1169 arg1 patients 1184:1191 at-risk and early RA patients 1163:1191 at-risk and early RA patients 1163:1191 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 7 69 theme B 966:966 arg1 cells 968:972 Memory and double negative (DN) B cells 934:972 cells 968:972 Memory and double negative (DN) B cells were prominent in all subgroups. 37192126 9 70 theme IgG 1199:1201 arg1 transcripts 1217:1227 Lung IgG variable gene transcripts 1194:1227 Lung IgG variable gene transcripts from ACPA-positive individuals 1194:1258 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 11 71 theme early 1665:1669 arg1 stages 1671:1676 , early stages 1663:1676 stages 1671:1676 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 9 72 theme gene 1212:1215 arg1 transcripts 1217:1227 Lung IgG variable gene transcripts 1194:1227 Lung IgG variable gene transcripts from ACPA-positive individuals 1194:1258 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 7 73 theme double 945:950 arg1 cells 968:972 Memory and double negative (DN) B cells 934:972 cells 968:972 Memory and double negative (DN) B cells were prominent in all subgroups. 37192126 1 74 dep OBJECTIVE 91:99 arg1 implicated 113:122 implicated 113:122 is implicated as a site for breaching tolerance prior to onset of seropositive RA 110:190 OBJECTIVE The lung is implicated as a site for breaching tolerance prior to onset of seropositive RA. 37192126 5 75 theme Monoclonal 692:701 arg1 ACPAs 703:707 Monoclonal ACPAs 692:707 Monoclonal ACPAs 692:707 Monoclonal ACPAs were tested for reactivity patterns and binding to neutrophils. 37192126 7 76 theme Memory 934:939 arg1 cells 968:972 Memory and double negative (DN) B cells 934:972 cells 968:972 Memory and double negative (DN) B cells were prominent in all subgroups. 37192126 11 77 theme RA 1695:1696 arg1 stages 1671:1676 , early stages 1663:1676 stages 1671:1676 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 0 78 theme disease 82:88 arg1 onset 73:77 the onset 69:77 the onset of disease 69:88 Rheumatoid arthritis specific autoimmunity in the lung before and at the onset of disease. 37192126 11 79 from evident 1625:1631 arg1 lungs 1636:1640 lungs 1636:1640 lungs before, as well as in, early stages of ACPA-positive RA 1636:1696 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 9 80 theme frequent 1266:1273 arg1 sites 1319:1323 frequent mutation-induced N-linked Fab glycosylation sites 1266:1323 frequent mutation-induced N-linked Fab glycosylation sites (p<0.001) 1266:1333 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 9 80 theme frequent 1266:1273 arg1 p<0.001 1326:1332 p<0.001 1326:1332 p<0.001 1326:1332 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 12 81 theme citrulline 1780:1789 arg1 autoimmunity 1791:1802 the citrulline autoimmunity 1776:1802 the citrulline autoimmunity preceding seropositive RA 1776:1828 Our findings add to the notion of lung mucosa being a site for initiation of the citrulline autoimmunity preceding seropositive RA. 37192126 3 82 attach isolated 489:496 arg1 BAL 503:505 BAL 503:505 BAL of individuals during the risk-RA phase and at RA diagnosis 503:565 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 3 82 attach isolated 489:496 arg2 METHODS 437:443 METHODS 437:443 METHODS Single B cells (n=7680) 437:467 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 11 83 from lungs 1636:1640 arg1 evident 1625:1631 evident 1625:1631 evident 1625:1631 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 9 84 theme N-linked 1292:1299 arg1 sites 1319:1323 frequent mutation-induced N-linked Fab glycosylation sites 1266:1323 frequent mutation-induced N-linked Fab glycosylation sites (p<0.001) 1266:1333 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 9 84 theme N-linked 1292:1299 arg1 p<0.001 1326:1332 p<0.001 1326:1332 p<0.001 1326:1332 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 3 85 dep METHODS 437:443 arg1 n=7680 461:466 n=7680 461:466 n=7680 461:466 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 3 85 dep METHODS 437:443 arg1 cells 454:458 Single B cells 445:458 METHODS Single B cells (n=7680) 437:467 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 0 86 from lung 50:53 arg1 specific 21:28 specific 21:28 specific 21:28 Rheumatoid arthritis specific autoimmunity in the lung before and at the onset of disease. 37192126 10 87 theme ACPAs 1402:1406 arg1 Two 1385:1387 Two 1385:1387 Two 1385:1387 Two of the lungs ACPAs bound to activated neutrophils, one from an at-risk individual and one from early RA. 37192126 10 87 theme ACPAs 1402:1406 arg1 ACPAs 1402:1406 the lungs ACPAs 1392:1406 the lungs ACPAs 1392:1406 Two of the lungs ACPAs bound to activated neutrophils, one from an at-risk individual and one from early RA. 37192126 4 88 theme monoclonal 661:670 arg1 transcripts 603:613 The Immunoglobulin variable region transcripts 568:613 The Immunoglobulin variable region transcripts 568:613 The Immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n=141). 37192126 4 88 theme monoclonal 661:670 arg1 n=141 684:688 n=141 684:688 n=141 684:688 The Immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n=141). 37192126 4 88 theme monoclonal 661:670 arg1 antibodies 672:681 monoclonal antibodies 661:681 monoclonal antibodies (n=141) 661:689 The Immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n=141). 37192126 3 89 from BAL 503:505 arg1 diagnosis 557:565 RA diagnosis 554:565 RA diagnosis 554:565 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 9 90 theme glycosylation 1305:1317 arg1 sites 1319:1323 frequent mutation-induced N-linked Fab glycosylation sites 1266:1323 frequent mutation-induced N-linked Fab glycosylation sites (p<0.001) 1266:1333 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 9 90 theme glycosylation 1305:1317 arg1 p<0.001 1326:1332 p<0.001 1326:1332 p<0.001 1326:1332 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 8 91 theme antibody 1012:1019 arg1 re-expression 1021:1033 antibody re-expression 1012:1033 antibody re-expression 1012:1033 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 9 92 link N-linked 1292:1299 arg1 sites 1319:1323 frequent mutation-induced N-linked Fab glycosylation sites 1266:1323 frequent mutation-induced N-linked Fab glycosylation sites (p<0.001) 1266:1333 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 9 92 link N-linked 1292:1299 arg1 p<0.001 1326:1332 p<0.001 1326:1332 p<0.001 1326:1332 Lung IgG variable gene transcripts from ACPA-positive individuals carry frequent mutation-induced N-linked Fab glycosylation sites (p<0.001), often in the framework-3 of the variable region. 37192126 6 93 theme cell 795:798 arg1 approach 800:807 our single cell approach 784:807 our single cell approach 784:807 RESULTS By our single cell approach, we found significantly increased proportions of B lymphocytes in autoantibody-positive as compared to negative individuals. 37192126 11 94 theme cell 1524:1527 arg1 differentiation 1543:1557 T cell driven B cell differentiation 1522:1557 T cell driven B cell differentiation 1522:1557 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 2 95 theme protein 360:366 arg1 individuals 393:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 anti-citrullinated protein antibody (ACPA)-positive individuals 341:403 To substantiate this, we have investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from early untreated RA patients (n=9) and anti-citrullinated protein antibody (ACPA)-positive individuals at risk of developing RA (n=3). 37192126 12 96 theme mucosa 1738:1743 arg1 notion 1723:1728 the notion 1719:1728 the notion of lung mucosa being a site for initiation of the citrulline autoimmunity preceding seropositive RA 1719:1828 Our findings add to the notion of lung mucosa being a site for initiation of the citrulline autoimmunity preceding seropositive RA. 37192126 3 97 theme Single 445:450 arg1 n=7680 461:466 n=7680 461:466 n=7680 461:466 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 3 97 theme Single 445:450 arg1 cells 454:458 Single B cells 445:458 METHODS Single B cells (n=7680) 437:467 METHODS Single B cells (n=7680) were phenotyped and isolated from BAL of individuals during the risk-RA phase and at RA diagnosis. 37192126 8 98 theme citrulline 1057:1066 arg1 clones 1081:1086 seven highly mutated citrulline autoreactive clones 1036:1086 seven highly mutated citrulline autoreactive clones 1036:1086 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 8 99 dep subsets 1129:1135 arg1 both 1155:1158 both 1155:1158 both 1155:1158 Upon antibody re-expression, seven highly mutated citrulline autoreactive clones originating from different memory B cell subsets where identified, both in at-risk and early RA patients. 37192126 10 100 theme early 1484:1488 arg1 RA 1490:1491 early RA 1484:1491 early RA 1484:1491 Two of the lungs ACPAs bound to activated neutrophils, one from an at-risk individual and one from early RA. 37192126 11 101 theme local 1573:1577 arg1 switching 1585:1593 local class switching 1573:1593 local class switching 1573:1593 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37192126 11 102 theme B 1536:1536 arg1 differentiation 1543:1557 T cell driven B cell differentiation 1522:1557 T cell driven B cell differentiation 1522:1557 CONCLUSION We conclude that T cell driven B cell differentiation, resulting in local class switching and somatic hypermutation are evident in lungs before, as well as in, early stages of ACPA-positive RA. 37115010 4 0 theme pathogenic 911:920 arg1 fungi 922:926 pathogenic fungi 911:926 pathogenic fungi 911:926 Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. 37115010 7 1 theme MoLOX-LA 1438:1445 arg1 DAD 1447:1449 the MoLOX-LA DAD 1434:1449 the MoLOX-LA DAD 1434:1449 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 2 2 theme dynamics 675:682 arg1 computations 689:700 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations 599:700 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations 599:700 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 7 3 theme Å 1697:1697 arg1 distance 1706:1713 a 4.9 Å Mn-C11 distance 1691:1713 a 4.9 Å Mn-C11 distance 1691:1713 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 3 4 theme catalytic 746:754 arg1 iron 777:780 the catalytic mononuclear, nonheme iron 742:780 iron 777:780 However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. 37115010 5 5 from structure 1021:1029 arg1 MoLOX 1121:1125 MoLOX 1121:1125 MoLOX complexed with LA 1121:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 5 5 from structure 1021:1029 arg1 oryzae 1113:1118 rice blast pathogen Magnaporthe oryzae 1081:1118 rice blast pathogen Magnaporthe oryzae 1081:1118 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 8 6 theme reactivity 1806:1815 arg1 differences 1817:1827 reactivity differences 1806:1827 reactivity differences across the LOX family 1806:1849 The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures. 37115010 4 7 theme mononuclear 943:953 arg1 metallocenters 960:973 active mononuclear Mn2+ metallocenters 936:973 active mononuclear Mn2+ metallocenters 936:973 Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. 37115010 3 8 theme iron 777:780 arg1 probe 844:848 a spin probe 837:848 a spin probe 837:848 However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. 37115010 3 8 theme iron 777:780 arg1 substitution 726:737 substitution 726:737 substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion 726:832 However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. 37115010 5 9 theme pathogen 1092:1099 arg1 MoLOX 1121:1125 MoLOX 1121:1125 MoLOX complexed with LA 1121:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 5 9 theme pathogen 1092:1099 arg1 oryzae 1113:1118 rice blast pathogen Magnaporthe oryzae 1081:1118 rice blast pathogen Magnaporthe oryzae 1081:1118 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 6 10 dep distance 1336:1343 arg1 DAD 1346:1348 DAD 1346:1348 DAD 1346:1348 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 7 11 theme MoLOX 1560:1564 arg1 complex 1566:1572 the MoLOX complex 1556:1572 the MoLOX complex 1556:1572 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 1 12 dep attempts 268:275 arg1 capture 280:286 capture 280:286 capture 280:286 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 1 12 dep attempts 268:275 arg1 unsuccessful 370:381 unsuccessful 370:381 unsuccessful 370:381 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 1 12 dep attempts 268:275 arg1 characterize 292:303 characterize 292:303 characterize LOX-substrate complexes by X-ray co-crystallography 292:355 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 0 13 theme Active 149:154 arg1 Lipoxygenase 179:190 an Active, N-Linked Glycosylated Lipoxygenase 146:190 an Active, N-Linked Glycosylated Lipoxygenase 146:190 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 1 14 theme cell-signaling 238:251 arg1 mediators 253:261 important cell-signaling mediators 228:261 important cell-signaling mediators 228:261 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 7 15 from that 1456:1459 arg1 difference 1420:1429 The difference 1416:1429 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation 1416:1660 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 2 16 theme double 623:628 arg1 ENDOR 641:645 ENDOR 641:645 ENDOR 641:645 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 16 theme double 623:628 arg1 resonance 630:638 13C/1H electron nuclear double resonance 599:638 13C/1H electron nuclear double resonance (ENDOR) spectroscopy 599:659 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 3 17 theme faithful 802:809 arg1 ion 830:832 the structurally faithful, yet inactive Mn2+ ion 785:832 the structurally faithful, yet inactive Mn2+ ion 785:832 However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. 37115010 5 18 theme LOX 1072:1074 arg1 structure 1021:1029 the ground-state active-site structure 992:1029 the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA 992:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 2 19 theme electron 606:613 arg1 ENDOR 641:645 ENDOR 641:645 ENDOR 641:645 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 19 theme electron 606:613 arg1 resonance 630:638 13C/1H electron nuclear double resonance 599:638 13C/1H electron nuclear double resonance (ENDOR) spectroscopy 599:659 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 6 20 theme Mn-bound 1303:1310 arg1 oxygen 1312:1317 Mn-bound oxygen 1303:1317 Mn-bound oxygen 1303:1317 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 5 21 theme rice 1081:1084 arg1 MoLOX 1121:1125 MoLOX 1121:1125 MoLOX complexed with LA 1121:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 5 21 theme rice 1081:1084 arg1 oryzae 1113:1118 rice blast pathogen Magnaporthe oryzae 1081:1118 rice blast pathogen Magnaporthe oryzae 1081:1118 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 3 22 theme Mn2+ 825:828 arg1 ion 830:832 the structurally faithful, yet inactive Mn2+ ion 785:832 the structurally faithful, yet inactive Mn2+ ion 785:832 However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. 37115010 6 23 theme 0.1 1409:1411 arg1 ± 1407:1407 ± 1407:1407 ± 1407:1407 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 0 24 dep Active 149:154 arg1 N-Linked 157:164 N-Linked 157:164 N-Linked 157:164 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 7 25 theme " 1630:1630 arg1 orientation 1650:1660 a "carboxylate-out" substrate-binding orientation 1612:1660 a "carboxylate-out" substrate-binding orientation 1612:1660 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 0 26 theme Lipoxygenase 179:190 arg1 Complex 135:141 the Enzyme-Substrate Complex 114:141 the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase 114:190 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 4 27 from animals 892:898 arg1 Fe-LOXs 868:874 canonical Fe-LOXs 858:874 canonical Fe-LOXs from plants and animals 858:898 Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. 37115010 3 28 theme spin 839:842 arg1 probe 844:848 a spin probe 837:848 a spin probe 837:848 However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. 37115010 3 28 theme spin 839:842 arg1 substitution 726:737 substitution 726:737 substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion 726:832 However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. 37115010 8 29 theme MoLOX 1897:1901 arg1 inhibitors 1903:1912 MoLOX inhibitors 1897:1912 MoLOX inhibitors 1897:1912 The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures. 37115010 4 30 from plants 881:886 arg1 Fe-LOXs 868:874 canonical Fe-LOXs 858:874 canonical Fe-LOXs from plants and animals 858:898 Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. 37115010 0 31 theme Enzyme-Substrate 118:133 arg1 Complex 135:141 the Enzyme-Substrate Complex 114:141 the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase 114:190 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 1 32 theme methods 432:438 arg1 development 394:404 development 394:404 development of alternative structural methods 394:438 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 4 33 theme canonical 858:866 arg1 Fe-LOXs 868:874 canonical Fe-LOXs 858:874 canonical Fe-LOXs from plants and animals 858:898 Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. 37115010 5 34 theme active-site 1009:1019 arg1 structure 1021:1029 the ground-state active-site structure 992:1029 the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA 992:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 0 35 theme 13C 0:2 arg1 Resonance 28:36 13C Electron Nuclear Double Resonance 0:36 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 0:191 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 1 36 theme LOX-substrate 305:317 arg1 complexes 319:327 LOX-substrate complexes 305:327 LOX-substrate complexes 305:327 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 8 37 theme LOX-substrate 1988:2000 arg1 structures 2002:2011 LOX-substrate structures 1988:2011 LOX-substrate structures 1988:2011 The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures. 37115010 2 38 theme soybean 496:502 arg1 lipoxygenase 504:515 soybean lipoxygenase 496:515 soybean lipoxygenase 496:515 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 38 theme soybean 496:502 arg1 SLO 518:520 SLO 518:520 SLO 518:520 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 39 theme complex 485:491 arg1 structure 468:476 the structure 464:476 the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA) 464:555 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 0 40 theme Nuclear 13:19 arg1 Resonance 28:36 13C Electron Nuclear Double Resonance 0:36 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 0:191 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 2 41 theme substrate 528:536 arg1 LA 553:554 LA 553:554 LA 553:554 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 41 theme substrate 528:536 arg1 acid 547:550 substrate linoleic acid 528:550 substrate linoleic acid (LA) 528:555 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 0 42 theme Resonance 28:36 arg1 Dynamics 68:75 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics 0:75 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 0:191 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 7 43 dep difference 1420:1429 arg1 whereas 1663:1669 whereas 1663:1669 whereas 1663:1669 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 6 44 theme 3.4 1403:1405 arg1 ± 1407:1407 ± 1407:1407 ± 1407:1407 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 0 45 theme Molecular 58:66 arg1 Dynamics 68:75 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics 0:75 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 0:191 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 5 46 theme ENDOR-guided 1177:1188 arg1 approach 1193:1200 the 13C/1H ENDOR-guided MD approach 1166:1200 the 13C/1H ENDOR-guided MD approach 1166:1200 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 5 47 theme fungal 1065:1070 arg1 LOX 1072:1074 the native, fully glycosylated fungal LOX 1034:1074 the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA 1034:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 7 48 theme " 1736:1736 arg1 orientation 1748:1758 a "carboxylate-in" substrate orientation 1719:1758 a "carboxylate-in" substrate orientation 1719:1758 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 5 49 theme native 1038:1043 arg1 LOX 1072:1074 the native, fully glycosylated fungal LOX 1034:1074 the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA 1034:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 8 50 theme inhibitors 1903:1912 arg1 development 1882:1892 development 1882:1892 development of MoLOX inhibitors 1882:1912 The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures. 37115010 7 51 theme DAD 1447:1449 arg1 difference 1420:1429 The difference 1416:1429 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation 1416:1660 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 7 52 theme Mn-C11 1699:1704 arg1 distance 1706:1713 a 4.9 Å Mn-C11 distance 1691:1713 a 4.9 Å Mn-C11 distance 1691:1713 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 8 53 theme structural 1781:1790 arg1 insights 1792:1799 structural insights 1781:1799 structural insights into reactivity differences across the LOX family 1781:1849 The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures. 37115010 7 54 dep complex 1475:1481 arg1 important 1513:1521 important 1513:1521 important 1513:1521 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 2 55 theme resonance 630:638 arg1 spectroscopy 648:659 13C/1H electron nuclear double resonance (ENDOR) spectroscopy 599:659 13C/1H electron nuclear double resonance (ENDOR) spectroscopy 599:659 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 3 56 theme nonheme 769:775 arg1 iron 777:780 the catalytic mononuclear, nonheme iron 742:780 iron 777:780 However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. 37115010 7 57 theme substrate-binding 1632:1648 arg1 orientation 1650:1660 a "carboxylate-out" substrate-binding orientation 1612:1660 a "carboxylate-out" substrate-binding orientation 1612:1660 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 1 58 theme Lipoxygenase 193:204 arg1 enzymes 212:218 Lipoxygenase (LOX) enzymes 193:218 Lipoxygenase (LOX) enzymes 193:218 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 8 59 theme MD 1964:1965 arg1 approach 1967:1974 the ENDOR-guided MD approach 1947:1974 the ENDOR-guided MD approach to describe LOX-substrate structures 1947:2011 The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures. 37115010 2 60 with complex 485:491 arg1 LA 553:554 LA 553:554 LA 553:554 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 60 with complex 485:491 arg1 acid 547:550 substrate linoleic acid 528:550 substrate linoleic acid (LA) 528:555 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 61 theme molecular 665:673 arg1 MD 685:686 MD 685:686 MD 685:686 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 61 theme molecular 665:673 arg1 dynamics 675:682 molecular dynamics 665:682 molecular dynamics (MD) 665:687 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 3 62 theme mononuclear 756:766 arg1 iron 777:780 the catalytic mononuclear, nonheme iron 742:780 iron 777:780 However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. 37115010 2 63 theme spectroscopy 648:659 arg1 computations 689:700 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations 599:700 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations 599:700 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 7 64 theme SLO 1675:1677 arg1 complex 1679:1685 the SLO complex 1671:1685 the SLO complex 1671:1685 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 4 65 theme active 936:941 arg1 metallocenters 960:973 active mononuclear Mn2+ metallocenters 936:973 active mononuclear Mn2+ metallocenters 936:973 Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. 37115010 5 66 dep native 1038:1043 arg1 glycosylated 1052:1063 glycosylated 1052:1063 glycosylated 1052:1063 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 5 67 theme Magnaporthe 1101:1111 arg1 MoLOX 1121:1125 MoLOX 1121:1125 MoLOX complexed with LA 1121:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 5 67 theme Magnaporthe 1101:1111 arg1 oryzae 1113:1118 rice blast pathogen Magnaporthe oryzae 1081:1118 rice blast pathogen Magnaporthe oryzae 1081:1118 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 1 68 theme important 228:236 arg1 mediators 253:261 important cell-signaling mediators 228:261 important cell-signaling mediators 228:261 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 4 69 theme Mn2+ 955:958 arg1 metallocenters 960:973 active mononuclear Mn2+ metallocenters 936:973 active mononuclear Mn2+ metallocenters 936:973 Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. 37115010 5 70 from oryzae 1113:1118 arg1 structure 1021:1029 the ground-state active-site structure 992:1029 the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA 992:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 5 70 from oryzae 1113:1118 arg1 LOX 1072:1074 the native, fully glycosylated fungal LOX 1034:1074 the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA 1034:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 0 71 theme Glycosylated 166:177 arg1 Lipoxygenase 179:190 an Active, N-Linked Glycosylated Lipoxygenase 146:190 an Active, N-Linked Glycosylated Lipoxygenase 146:190 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 2 72 theme nuclear 615:621 arg1 ENDOR 641:645 ENDOR 641:645 ENDOR 641:645 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 72 theme nuclear 615:621 arg1 resonance 630:638 13C/1H electron nuclear double resonance 599:638 13C/1H electron nuclear double resonance (ENDOR) spectroscopy 599:659 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 6 73 theme hydrogen 1252:1259 arg1 donor 1261:1265 the hydrogen donor 1248:1265 the hydrogen donor 1248:1265 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 6 73 theme hydrogen 1252:1259 arg1 distance 1336:1343 donor-acceptor distance 1321:1343 donor-acceptor distance 1321:1343 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 4 74 from fungi 922:926 arg1 LOXs 901:904 LOXs 901:904 LOXs from pathogenic fungi 901:926 Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. 37115010 2 75 theme 13C/1H 599:604 arg1 ENDOR 641:645 ENDOR 641:645 ENDOR 641:645 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 75 theme 13C/1H 599:604 arg1 resonance 630:638 13C/1H electron nuclear double resonance 599:638 13C/1H electron nuclear double resonance (ENDOR) spectroscopy 599:659 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 5 76 theme blast 1086:1090 arg1 MoLOX 1121:1125 MoLOX 1121:1125 MoLOX complexed with LA 1121:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 5 76 theme blast 1086:1090 arg1 oryzae 1113:1118 rice blast pathogen Magnaporthe oryzae 1081:1118 rice blast pathogen Magnaporthe oryzae 1081:1118 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 6 77 theme important 1221:1229 arg1 Å 1413:1413 3.4 ± 0.1 Å 1403:1413 3.4 ± 0.1 Å 1403:1413 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 6 77 theme important 1221:1229 arg1 distance 1231:1238 The catalytically important distance 1203:1238 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion 1203:1398 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 1 78 theme alternative 409:419 arg1 methods 432:438 alternative structural methods 409:438 alternative structural methods 409:438 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 2 79 theme linoleic 538:545 arg1 LA 553:554 LA 553:554 LA 553:554 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 79 theme linoleic 538:545 arg1 acid 547:550 substrate linoleic acid 528:550 substrate linoleic acid (LA) 528:555 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 2 80 theme computations 689:700 arg1 integration 584:594 the integration 580:594 the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations 580:700 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 6 81 theme MoLOX-LA 1359:1366 arg1 complex 1368:1374 the MoLOX-LA complex 1355:1374 the MoLOX-LA complex derived in this fashion 1355:1398 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 7 82 theme carboxylate-out 1615:1629 arg1 orientation 1650:1660 a "carboxylate-out" substrate-binding orientation 1612:1660 a "carboxylate-out" substrate-binding orientation 1612:1660 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 8 83 theme LOX 1840:1842 arg1 family 1844:1849 the LOX family 1836:1849 the LOX family 1836:1849 The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures. 37115010 0 84 theme Complex 135:141 arg1 Structure 101:109 the Structure 97:109 the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase 97:190 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 1 85 theme structural 421:430 arg1 methods 432:438 alternative structural methods 409:438 alternative structural methods 409:438 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 5 86 theme ground-state 996:1007 arg1 structure 1021:1029 the ground-state active-site structure 992:1029 the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA 992:1143 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 4 87 contain contain 928:934 arg2 metallocenters 960:973 active mononuclear Mn2+ metallocenters 936:973 active mononuclear Mn2+ metallocenters 936:973 Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. 37115010 4 87 contain contain 928:934 arg1 LOXs 901:904 LOXs 901:904 LOXs from pathogenic fungi 901:926 Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. 37115010 0 88 theme Electron 4:11 arg1 Resonance 28:36 13C Electron Nuclear Double Resonance 0:36 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 0:191 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 3 89 dep faithful 802:809 arg1 inactive 816:823 inactive 816:823 inactive 816:823 However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. 37115010 7 90 theme Å 1606:1606 arg1 distance 1590:1597 a Mn-C11 distance 1581:1597 a Mn-C11 distance of 5.4 Å 1581:1606 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 7 90 theme Å 1606:1606 arg1 orientation 1650:1660 a "carboxylate-out" substrate-binding orientation 1612:1660 a "carboxylate-out" substrate-binding orientation 1612:1660 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 2 91 theme lipoxygenase 504:515 arg1 complex 485:491 the complex 481:491 the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA) 481:555 We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. 37115010 0 92 theme Double 21:26 arg1 Resonance 28:36 13C Electron Nuclear Double Resonance 0:36 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 0:191 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 7 93 contain has 1687:1689 arg2 distance 1706:1713 a 4.9 Å Mn-C11 distance 1691:1713 a 4.9 Å Mn-C11 distance 1691:1713 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 7 93 contain has 1687:1689 arg2 orientation 1748:1758 a "carboxylate-in" substrate orientation 1719:1758 a "carboxylate-in" substrate orientation 1719:1758 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 7 93 contain has 1687:1689 arg1 complex 1679:1685 the SLO complex 1671:1685 the SLO complex 1671:1685 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 0 94 theme Spectroscopy-Guided 38:56 arg1 Dynamics 68:75 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics 0:75 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 0:191 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 1 95 theme X-ray 332:336 arg1 co-crystallography 338:355 X-ray co-crystallography 332:355 X-ray co-crystallography 332:355 Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. 37115010 0 96 dep Dynamics 68:75 arg1 Reveal 90:95 Reveal 90:95 Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase 90:190 13C Electron Nuclear Double Resonance Spectroscopy-Guided Molecular Dynamics Computations Reveal the Structure of the Enzyme-Substrate Complex of an Active, N-Linked Glycosylated Lipoxygenase. 37115010 7 97 theme Mn-C11 1583:1588 arg1 distance 1590:1597 a Mn-C11 distance 1581:1597 a Mn-C11 distance of 5.4 Å 1581:1606 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 8 98 theme approach 1967:1974 arg1 robustness 1933:1942 the robustness 1929:1942 the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures 1929:2011 The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures. 37115010 5 99 theme 13C/1H 1170:1175 arg1 approach 1193:1200 the 13C/1H ENDOR-guided MD approach 1166:1200 the 13C/1H ENDOR-guided MD approach 1166:1200 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 7 100 theme ± 1488:1488 arg1 complex 1475:1481 the SLO-LA complex 1464:1481 the SLO-LA complex 1464:1481 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 7 100 theme ± 1488:1488 arg1 Å 1494:1494 3.1 ± 0.1 Å 1484:1494 3.1 ± 0.1 Å 1484:1494 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 8 101 theme ENDOR-guided 1951:1962 arg1 approach 1967:1974 the ENDOR-guided MD approach 1947:1974 the ENDOR-guided MD approach to describe LOX-substrate structures 1947:2011 The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures. 37115010 6 102 theme donor-acceptor 1321:1334 arg1 distance 1336:1343 donor-acceptor distance 1321:1343 donor-acceptor distance 1321:1343 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 6 102 theme donor-acceptor 1321:1334 arg1 donor 1261:1265 the hydrogen donor 1248:1265 the hydrogen donor 1248:1265 The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. 37115010 5 103 theme MD 1190:1191 arg1 approach 1193:1200 the 13C/1H ENDOR-guided MD approach 1166:1200 the 13C/1H ENDOR-guided MD approach 1166:1200 Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. 37115010 7 104 theme substrate 1738:1746 arg1 orientation 1748:1758 a "carboxylate-in" substrate orientation 1719:1758 a "carboxylate-in" substrate orientation 1719:1758 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 7 105 theme SLO-LA 1468:1473 arg1 complex 1475:1481 the SLO-LA complex 1464:1481 the SLO-LA complex 1464:1481 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 7 105 theme SLO-LA 1468:1473 arg1 Å 1494:1494 3.1 ± 0.1 Å 1484:1494 3.1 ± 0.1 Å 1484:1494 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 37115010 7 106 theme carboxylate-in 1722:1735 arg1 orientation 1748:1758 a "carboxylate-in" substrate orientation 1719:1758 a "carboxylate-in" substrate orientation 1719:1758 The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. 36948234 8 0 dep G3 1009:1010 arg1 7/8 1013:1015 7/8 1013:1015 7/8 1013:1015 The G genotypes were G3 (7/8) and G6 (1/8) among the 8 RVA positives, while the P genotypes were P[6] (4/8) and P[8] (2), and the other two were untypeable. 36948234 8 1 theme P 1068:1068 arg1 P[6 1085:1087 P[6 1085:1087 P[6 1085:1087 The G genotypes were G3 (7/8) and G6 (1/8) among the 8 RVA positives, while the P genotypes were P[6] (4/8) and P[8] (2), and the other two were untypeable. 36948234 8 1 theme P 1068:1068 arg1 genotypes 1070:1078 the P genotypes 1064:1078 the P genotypes 1064:1078 The G genotypes were G3 (7/8) and G6 (1/8) among the 8 RVA positives, while the P genotypes were P[6] (4/8) and P[8] (2), and the other two were untypeable. 36948234 4 2 theme samples 585:591 arg1 total 565:569 A total 563:569 A total of 169 faecal samples 563:591 A total of 169 faecal samples were collected from under-five with diarrhea in Mbeya, Iringa and Morogoro regions of Tanzania. 36948234 13 3 theme wild 1961:1964 arg1 type 1966:1969 the wild type G3 and P[8 1957:1980 type 1966:1969 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 11 4 theme human 1488:1492 arg1 G3P[6 1494:1498 human G3P[6] 1488:1499 human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries 1488:1586 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 11 5 theme phylogenic 1404:1413 arg1 analysis 1415:1422 The phylogenic analysis 1400:1422 The phylogenic analysis 1400:1422 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 1 6 theme genomic 159:165 arg1 characterization 167:182 Rotavirus group A genomic characterization 141:182 Rotavirus group A genomic characterization 141:182 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 13 7 gly glycosylation 1929:1941 arg2 sites 1943:1947 N-linked glycosylation sites 1920:1947 N-linked glycosylation sites 1920:1947 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 13 8 from impact 2052:2057 arg1 effectiveness 2091:2103 vaccine effectiveness 2083:2103 vaccine effectiveness 2083:2103 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 15 9 theme genotypes 2396:2404 arg1 importance 2313:2322 the importance 2309:2322 the importance of rotavirus genotype monitoring 2309:2355 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 15 9 theme genotypes 2396:2404 arg1 analysis 2369:2376 genomic analysis 2361:2376 genomic analysis of representative genotypes 2361:2404 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 4 10 from diarrhea 629:636 arg1 Iringa 648:653 Iringa 648:653 Iringa 648:653 A total of 169 faecal samples were collected from under-five with diarrhea in Mbeya, Iringa and Morogoro regions of Tanzania. 36948234 4 10 from diarrhea 629:636 arg1 Mbeya 641:645 Mbeya 641:645 Mbeya 641:645 A total of 169 faecal samples were collected from under-five with diarrhea in Mbeya, Iringa and Morogoro regions of Tanzania. 36948234 4 10 from diarrhea 629:636 arg1 Morogoro 659:666 Morogoro 659:666 Morogoro 659:666 A total of 169 faecal samples were collected from under-five with diarrhea in Mbeya, Iringa and Morogoro regions of Tanzania. 36948234 5 11 theme G 805:805 arg1 genotypes 813:821 the G and P genotypes 801:821 the G and P genotypes 801:821 The RVA were screened in children under five with diarrhea using reverse transcription PCR for VP7 and VP4, and the G and P genotypes were determined using Sanger dideoxynucleotide cycle sequencing. 36948234 11 12 theme common 1635:1640 arg1 ancestor 1642:1649 a common ancestor 1633:1649 a common ancestor 1633:1649 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 13 13 theme N-linked 1920:1927 arg1 sites 1943:1947 N-linked glycosylation sites 1920:1947 N-linked glycosylation sites 1920:1947 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 15 14 theme equine-like 2249:2259 arg1 G3 2261:2262 novel equine-like G3 2243:2262 novel equine-like G3 2243:2262 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 5 15 theme P 811:811 arg1 genotypes 813:821 the G and P genotypes 801:821 the G and P genotypes 801:821 The RVA were screened in children under five with diarrhea using reverse transcription PCR for VP7 and VP4, and the G and P genotypes were determined using Sanger dideoxynucleotide cycle sequencing. 36948234 10 16 from children 1288:1295 arg1 isolates 1274:1281 the circulating G3P[8] and G3P[6] isolates 1240:1281 isolates 1274:1281 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 10 16 from children 1288:1295 arg1 G3P[8 1256:1260 the circulating G3P[8] and G3P[6] isolates 1240:1281 G3P[8 1256:1260 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 13 17 theme acid 1877:1880 arg1 differences 1882:1892 amino acid differences 1871:1892 amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] 1871:1981 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 11 18 theme other 1564:1568 arg1 Uganda 1545:1550 Uganda 1545:1550 Uganda 1545:1550 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 11 18 theme other 1564:1568 arg1 countries 1578:1586 other African countries 1564:1586 other African countries 1564:1586 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 13 19 theme differences 2068:2078 arg1 impact 2052:2057 the impact 2048:2057 the impact of these differences on vaccine effectiveness 2048:2103 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 5 20 theme dideoxynucleotide 852:868 arg1 sequencing 876:885 Sanger dideoxynucleotide cycle sequencing 845:885 Sanger dideoxynucleotide cycle sequencing 845:885 The RVA were screened in children under five with diarrhea using reverse transcription PCR for VP7 and VP4, and the G and P genotypes were determined using Sanger dideoxynucleotide cycle sequencing. 36948234 1 21 theme possible 285:292 arg1 transmission 307:318 possible interspecies transmission 285:318 possible interspecies transmission 285:318 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 5 22 theme reverse 754:760 arg1 PCR 776:778 reverse transcription PCR 754:778 reverse transcription PCR for VP7 and VP4 754:794 The RVA were screened in children under five with diarrhea using reverse transcription PCR for VP7 and VP4, and the G and P genotypes were determined using Sanger dideoxynucleotide cycle sequencing. 36948234 11 23 dep strains 1610:1616 arg1 descended 1618:1626 descended 1618:1626 strains descended from a common ancestor 1610:1649 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 7 24 theme overall 953:959 arg1 rate 965:968 The overall RVA rate 949:968 The overall RVA rate 949:968 The overall RVA rate was 4.7% (8/169). 36948234 7 24 theme overall 953:959 arg1 % 977:977 4.7% 974:977 4.7% (8/169) 974:985 The overall RVA rate was 4.7% (8/169). 36948234 1 25 theme group 151:155 arg1 A 157:157 Rotavirus group A 141:157 Rotavirus group A genomic characterization 141:182 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 15 26 theme strains 2287:2293 arg1 emergence 2230:2238 the emergence 2226:2238 the emergence of novel equine-like G3 and bovine-like G6 RVA strains 2226:2293 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 2 27 theme A 422:422 arg1 strains 424:430 the rotavirus group A strains 402:430 the rotavirus group A strains circulating in Tanzania 402:454 However, little is known about the genetic diversity and genomic relationship of the rotavirus group A strains circulating in Tanzania. 36948234 1 28 theme reassortment 261:272 arg1 events 274:279 reassortment events 261:279 reassortment events 261:279 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 15 29 theme G6 2280:2281 arg1 RVA 2283:2285 bovine-like G6 RVA 2268:2285 bovine-like G6 RVA 2268:2285 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 9 30 theme genotype 1183:1190 arg1 G3P[6 1145:1149 G3P[6 1145:1149 G3P[6 1145:1149 G3P[6] and G3P[8] were the identified genotype combinations. 36948234 9 30 theme genotype 1183:1190 arg1 G3P[8 1156:1160 G3P[8 1156:1160 G3P[8 1156:1160 G3P[6] and G3P[8] were the identified genotype combinations. 36948234 9 30 theme genotype 1183:1190 arg1 combinations 1192:1203 the identified genotype combinations 1168:1203 the identified genotype combinations 1168:1203 G3P[6] and G3P[8] were the identified genotype combinations. 36948234 0 31 theme Genetic 0:6 arg1 diversity 8:16 Genetic diversity 0:16 Genetic diversity 0:16 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 12 32 theme identified 1703:1712 arg1 G3P[P8 1726:1731 previously identified equine-like G3P[P8] 1692:1732 previously identified equine-like G3P[P8] from Kenya 1692:1743 Whereas, G3P[8] were closely related to previously identified equine-like G3P[P8] from Kenya, Japan, Thailand, Brazil, and Taiwan, implying that this strain was introduced rather than reassortment events. 36948234 2 33 theme strains 424:430 arg1 diversity 364:372 genetic diversity 356:372 genetic diversity 356:372 However, little is known about the genetic diversity and genomic relationship of the rotavirus group A strains circulating in Tanzania. 36948234 2 33 theme strains 424:430 arg1 relationship 386:397 genomic relationship 378:397 genomic relationship 378:397 However, little is known about the genetic diversity and genomic relationship of the rotavirus group A strains circulating in Tanzania. 36948234 9 34 theme identified 1172:1181 arg1 G3P[6 1145:1149 G3P[6 1145:1149 G3P[6 1145:1149 G3P[6] and G3P[8] were the identified genotype combinations. 36948234 9 34 theme identified 1172:1181 arg1 G3P[8 1156:1160 G3P[8 1156:1160 G3P[8 1156:1160 G3P[6] and G3P[8] were the identified genotype combinations. 36948234 9 34 theme identified 1172:1181 arg1 combinations 1192:1203 the identified genotype combinations 1168:1203 the identified genotype combinations 1168:1203 G3P[6] and G3P[8] were the identified genotype combinations. 36948234 13 35 theme further 2026:2032 arg1 research 2034:2041 further research 2026:2041 further research into the impact of these differences on vaccine effectiveness 2026:2103 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 15 36 from time 2198:2201 arg1 Tanzania 2206:2213 Tanzania 2206:2213 Tanzania 2206:2213 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 13 37 from sites 1943:1947 arg1 differences 1882:1892 amino acid differences 1871:1892 amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] 1871:1981 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 2 38 theme group 416:420 arg1 strains 424:430 the rotavirus group A strains 402:430 the rotavirus group A strains circulating in Tanzania 402:454 However, little is known about the genetic diversity and genomic relationship of the rotavirus group A strains circulating in Tanzania. 36948234 5 39 theme Sanger 845:850 arg1 sequencing 876:885 Sanger dideoxynucleotide cycle sequencing 845:885 Sanger dideoxynucleotide cycle sequencing 845:885 The RVA were screened in children under five with diarrhea using reverse transcription PCR for VP7 and VP4, and the G and P genotypes were determined using Sanger dideoxynucleotide cycle sequencing. 36948234 10 40 theme genome 1349:1354 arg1 I2-R2-C2-M2-Ax-N2-T2-E2-H2 1371:1396 I2-R2-C2-M2-Ax-N2-T2-E2-H2 1371:1396 I2-R2-C2-M2-Ax-N2-T2-E2-H2 1371:1396 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 10 40 theme genome 1349:1354 arg1 configuration 1356:1368 a DS-1-like genome configuration 1337:1368 a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2) 1337:1397 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 11 41 theme neighboring 1515:1525 arg1 countries 1527:1535 neighboring countries 1515:1535 neighboring countries such as Uganda 1515:1550 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 11 41 theme neighboring 1515:1525 arg1 Uganda 1545:1550 Uganda 1545:1550 Uganda 1545:1550 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 3 42 theme RVA 497:499 arg1 genotypes 501:509 RVA genotypes 497:509 RVA genotypes 497:509 The genetic and genomic relationship of RVA genotypes was investigated in children under the age of five. 36948234 0 43 theme G3P[6 42:46 arg1 G3P[8 65:69 equine-like G3P[8 53:69 equine-like G3P[8 53:69 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 0 43 theme G3P[6 42:46 arg1 diversity 8:16 Genetic diversity 0:16 Genetic diversity 0:16 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 0 43 theme G3P[6 42:46 arg1 analysis 30:37 Genomic analysis 22:37 Genomic analysis 22:37 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 2 44 theme rotavirus 406:414 arg1 strains 424:430 the rotavirus group A strains 402:430 the rotavirus group A strains circulating in Tanzania 402:454 However, little is known about the genetic diversity and genomic relationship of the rotavirus group A strains circulating in Tanzania. 36948234 1 45 theme rotavirus 232:240 arg1 diversity 242:250 rotavirus diversity 232:250 rotavirus diversity 232:250 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 8 46 theme RVA 1043:1045 arg1 positives 1047:1055 the 8 RVA positives 1037:1055 the 8 RVA positives 1037:1055 The G genotypes were G3 (7/8) and G6 (1/8) among the 8 RVA positives, while the P genotypes were P[6] (4/8) and P[8] (2), and the other two were untypeable. 36948234 12 47 theme reassortment 1836:1847 arg1 events 1849:1854 reassortment events 1836:1854 reassortment events 1836:1854 Whereas, G3P[8] were closely related to previously identified equine-like G3P[P8] from Kenya, Japan, Thailand, Brazil, and Taiwan, implying that this strain was introduced rather than reassortment events. 36948234 0 48 from Southern 100:107 arg1 Under-five 84:93 Under-five 84:93 Under-five 84:93 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 2 49 theme genetic 356:362 arg1 diversity 364:372 genetic diversity 356:372 genetic diversity 356:372 However, little is known about the genetic diversity and genomic relationship of the rotavirus group A strains circulating in Tanzania. 36948234 15 50 theme genotype 2337:2344 arg1 monitoring 2346:2355 rotavirus genotype monitoring 2327:2355 rotavirus genotype monitoring 2327:2355 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 6 51 theme Whole-genome 888:899 arg1 sequencing 901:910 Whole-genome sequencing 888:910 Whole-genome sequencing 888:910 Whole-genome sequencing was performed on selected genotypes. 36948234 10 52 theme five 1314:1317 arg1 age 1307:1309 the age 1303:1309 the age of five with diarrhea 1303:1331 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 3 53 theme genetic 461:467 arg1 relationship 481:492 The genetic and genomic relationship 457:492 The genetic and genomic relationship of RVA genotypes 457:509 The genetic and genomic relationship of RVA genotypes was investigated in children under the age of five. 36948234 5 54 theme cycle 870:874 arg1 sequencing 876:885 Sanger dideoxynucleotide cycle sequencing 845:885 Sanger dideoxynucleotide cycle sequencing 845:885 The RVA were screened in children under five with diarrhea using reverse transcription PCR for VP7 and VP4, and the G and P genotypes were determined using Sanger dideoxynucleotide cycle sequencing. 36948234 4 55 theme faecal 578:583 arg1 samples 585:591 169 faecal samples 574:591 169 faecal samples 574:591 A total of 169 faecal samples were collected from under-five with diarrhea in Mbeya, Iringa and Morogoro regions of Tanzania. 36948234 13 56 from epitopes 1907:1914 arg1 differences 1882:1892 amino acid differences 1871:1892 amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] 1871:1981 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 1 57 theme A 157:157 arg1 characterization 167:182 Rotavirus group A genomic characterization 141:182 Rotavirus group A genomic characterization 141:182 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 14 58 theme VP7 2146:2148 arg1 analysis 2134:2141 The phylogenic analysis 2119:2141 The phylogenic analysis of VP7 2119:2148 The phylogenic analysis of VP7 also identified a bovine-like G6. 36948234 10 59 theme circulating 1244:1254 arg1 G3P[8 1256:1260 the circulating G3P[8] and G3P[6] isolates 1240:1281 G3P[8 1256:1260 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 3 60 theme five 557:560 arg1 age 550:552 the age 546:552 the age of five 546:560 The genetic and genomic relationship of RVA genotypes was investigated in children under the age of five. 36948234 0 61 dep Southern 100:107 arg1 Highlands 109:117 Highlands 109:117 Highlands 109:117 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 0 61 dep Southern 100:107 arg1 Tanzania 131:138 Tanzania 131:138 Tanzania 131:138 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 4 62 with under-five 613:622 arg1 diarrhea 629:636 diarrhea 629:636 diarrhea in Mbeya, Iringa and Morogoro 629:666 A total of 169 faecal samples were collected from under-five with diarrhea in Mbeya, Iringa and Morogoro regions of Tanzania. 36948234 15 63 theme representative 2381:2394 arg1 genotypes 2396:2404 representative genotypes 2381:2404 representative genotypes 2381:2404 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 13 64 dep type 1966:1969 arg1 G3 1971:1972 G3 1971:1972 G3 1971:1972 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 13 65 theme glycosylation 1929:1941 arg1 sites 1943:1947 N-linked glycosylation sites 1920:1947 N-linked glycosylation sites 1920:1947 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 15 66 theme G3 2261:2262 arg1 strains 2287:2293 novel equine-like G3 and bovine-like G6 RVA strains 2243:2293 novel equine-like G3 and bovine-like G6 RVA strains 2243:2293 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 14 67 theme phylogenic 2123:2132 arg1 analysis 2134:2141 The phylogenic analysis 2119:2141 The phylogenic analysis of VP7 2119:2148 The phylogenic analysis of VP7 also identified a bovine-like G6. 36948234 15 68 theme novel 2243:2247 arg1 G3 2261:2262 novel equine-like G3 2243:2262 novel equine-like G3 2243:2262 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 12 69 from Kenya 1739:1743 arg1 G3P[P8 1726:1731 previously identified equine-like G3P[P8] 1692:1732 previously identified equine-like G3P[P8] from Kenya 1692:1743 Whereas, G3P[8] were closely related to previously identified equine-like G3P[P8] from Kenya, Japan, Thailand, Brazil, and Taiwan, implying that this strain was introduced rather than reassortment events. 36948234 11 70 theme African 1570:1576 arg1 Uganda 1545:1550 Uganda 1545:1550 Uganda 1545:1550 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 11 70 theme African 1570:1576 arg1 countries 1578:1586 other African countries 1564:1586 other African countries 1564:1586 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 0 71 theme equine-like 53:63 arg1 G3P[8 65:69 equine-like G3P[8 53:69 equine-like G3P[8 53:69 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 13 72 theme antigenic 1897:1905 arg1 epitopes 1907:1914 antigenic epitopes 1897:1914 antigenic epitopes 1897:1914 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 10 73 contain had 1333:1335 arg1 isolates 1274:1281 the circulating G3P[8] and G3P[6] isolates 1240:1281 isolates 1274:1281 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 10 73 contain had 1333:1335 arg1 G3P[8 1256:1260 the circulating G3P[8] and G3P[6] isolates 1240:1281 G3P[8 1256:1260 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 10 73 contain had 1333:1335 arg2 I2-R2-C2-M2-Ax-N2-T2-E2-H2 1371:1396 I2-R2-C2-M2-Ax-N2-T2-E2-H2 1371:1396 I2-R2-C2-M2-Ax-N2-T2-E2-H2 1371:1396 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 10 73 contain had 1333:1335 arg2 configuration 1356:1368 a DS-1-like genome configuration 1337:1368 a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2) 1337:1397 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 13 74 link N-linked 1920:1927 arg1 sites 1943:1947 N-linked glycosylation sites 1920:1947 N-linked glycosylation sites 1920:1947 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 8 75 theme G 992:992 arg1 genotypes 994:1002 The G genotypes 988:1002 The G genotypes 988:1002 The G genotypes were G3 (7/8) and G6 (1/8) among the 8 RVA positives, while the P genotypes were P[6] (4/8) and P[8] (2), and the other two were untypeable. 36948234 8 75 theme G 992:992 arg1 G3 1009:1010 G3 1009:1010 G3 (7/8) 1009:1016 The G genotypes were G3 (7/8) and G6 (1/8) among the 8 RVA positives, while the P genotypes were P[6] (4/8) and P[8] (2), and the other two were untypeable. 36948234 1 76 theme Rotavirus 141:149 arg1 A 157:157 Rotavirus group A 141:157 Rotavirus group A genomic characterization 141:182 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 4 77 theme Tanzania 679:686 arg1 regions 668:674 under-five with diarrhea in Mbeya, Iringa and Morogoro regions 613:674 under-five with diarrhea in Mbeya, Iringa and Morogoro regions of Tanzania 613:686 A total of 169 faecal samples were collected from under-five with diarrhea in Mbeya, Iringa and Morogoro regions of Tanzania. 36948234 13 78 theme amino 1871:1875 arg1 differences 1882:1892 amino acid differences 1871:1892 amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] 1871:1981 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 7 79 theme RVA 961:963 arg1 rate 965:968 The overall RVA rate 949:968 The overall RVA rate 949:968 The overall RVA rate was 4.7% (8/169). 36948234 7 79 theme RVA 961:963 arg1 % 977:977 4.7% 974:977 4.7% (8/169) 974:985 The overall RVA rate was 4.7% (8/169). 36948234 10 80 theme genomic 1210:1216 arg1 analysis 1218:1225 The genomic analysis 1206:1225 The genomic analysis 1206:1225 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 10 81 theme G3P[6 1267:1271 arg1 isolates 1274:1281 the circulating G3P[8] and G3P[6] isolates 1240:1281 isolates 1274:1281 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 15 82 theme first 2192:2196 arg1 time 2198:2201 the first time 2188:2201 the first time in Tanzania 2188:2213 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 13 83 theme vaccine 2083:2089 arg1 effectiveness 2091:2103 vaccine effectiveness 2083:2103 vaccine effectiveness 2083:2103 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 2 84 dep diversity 364:372 arg1 the 352:354 the 352:354 the 352:354 However, little is known about the genetic diversity and genomic relationship of the rotavirus group A strains circulating in Tanzania. 36948234 12 85 theme equine-like 1714:1724 arg1 G3P[P8 1726:1731 previously identified equine-like G3P[P8] 1692:1732 previously identified equine-like G3P[P8] from Kenya 1692:1743 Whereas, G3P[8] were closely related to previously identified equine-like G3P[P8] from Kenya, Japan, Thailand, Brazil, and Taiwan, implying that this strain was introduced rather than reassortment events. 36948234 15 86 theme RVA 2283:2285 arg1 strains 2287:2293 novel equine-like G3 and bovine-like G6 RVA strains 2243:2293 novel equine-like G3 and bovine-like G6 RVA strains 2243:2293 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 2 87 theme genomic 378:384 arg1 relationship 386:397 genomic relationship 378:397 genomic relationship 378:397 However, little is known about the genetic diversity and genomic relationship of the rotavirus group A strains circulating in Tanzania. 36948234 0 88 theme Genomic 22:28 arg1 analysis 30:37 Genomic analysis 22:37 Genomic analysis 22:37 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 15 89 theme bovine-like 2268:2278 arg1 RVA 2283:2285 bovine-like G6 RVA 2268:2285 bovine-like G6 RVA 2268:2285 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 3 90 theme genomic 473:479 arg1 relationship 481:492 The genetic and genomic relationship 457:492 The genetic and genomic relationship of RVA genotypes 457:509 The genetic and genomic relationship of RVA genotypes was investigated in children under the age of five. 36948234 5 91 theme transcription 762:774 arg1 PCR 776:778 reverse transcription PCR 754:778 reverse transcription PCR for VP7 and VP4 754:794 The RVA were screened in children under five with diarrhea using reverse transcription PCR for VP7 and VP4, and the G and P genotypes were determined using Sanger dideoxynucleotide cycle sequencing. 36948234 1 92 theme interspecies 294:305 arg1 transmission 307:318 possible interspecies transmission 285:318 possible interspecies transmission 285:318 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 0 93 theme Under-five 84:93 arg1 Children 75:82 Children 75:82 Children Under-five from Southern Highlands and Eastern Tanzania 75:138 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 10 94 theme DS-1-like 1339:1347 arg1 I2-R2-C2-M2-Ax-N2-T2-E2-H2 1371:1396 I2-R2-C2-M2-Ax-N2-T2-E2-H2 1371:1396 I2-R2-C2-M2-Ax-N2-T2-E2-H2 1371:1396 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 10 94 theme DS-1-like 1339:1347 arg1 configuration 1356:1368 a DS-1-like genome configuration 1337:1368 a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2) 1337:1397 The genomic analysis reveals that the circulating G3P[8] and G3P[6] isolates from children under the age of five with diarrhea had a DS-1-like genome configuration (I2-R2-C2-M2-Ax-N2-T2-E2-H2). 36948234 3 95 theme genotypes 501:509 arg1 relationship 481:492 The genetic and genomic relationship 457:492 The genetic and genomic relationship of RVA genotypes 457:509 The genetic and genomic relationship of RVA genotypes was investigated in children under the age of five. 36948234 15 96 theme genomic 2361:2367 arg1 analysis 2369:2376 genomic analysis 2361:2376 genomic analysis of representative genotypes 2361:2404 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 13 97 theme vaccine 1995:2001 arg1 strains 2003:2009 vaccine strains 1995:2009 vaccine strains 1995:2009 We discovered amino acid differences at antigenic epitopes and N-linked glycosylation sites between the wild type G3 and P[8] compared to vaccine strains, implying that further research into the impact of these differences on vaccine effectiveness is warranted. 36948234 11 98 theme G3P[6 1457:1461 arg1 segments 1445:1452 all 11 segments 1438:1452 all 11 segments of G3P[6] 1438:1462 The phylogenic analysis revealed that all 11 segments of G3P[6] were closely related to human G3P[6] identified in neighboring countries such as Uganda, Kenya, and other African countries, implying that G3P[6] strains descended from a common ancestor. 36948234 15 99 theme monitoring 2346:2355 arg1 importance 2313:2322 the importance 2309:2322 the importance of rotavirus genotype monitoring 2309:2355 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 15 99 theme monitoring 2346:2355 arg1 analysis 2369:2376 genomic analysis 2361:2376 genomic analysis of representative genotypes 2361:2404 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 0 100 dep diversity 8:16 arg1 Children 75:82 Children 75:82 Children Under-five from Southern Highlands and Eastern Tanzania 75:138 Genetic diversity and Genomic analysis of G3P[6] and equine-like G3P[8] in Children Under-five from Southern Highlands and Eastern Tanzania. 36948234 4 101 theme under-five 613:622 arg1 regions 668:674 under-five with diarrhea in Mbeya, Iringa and Morogoro regions 613:674 under-five with diarrhea in Mbeya, Iringa and Morogoro regions of Tanzania 613:686 A total of 169 faecal samples were collected from under-five with diarrhea in Mbeya, Iringa and Morogoro regions of Tanzania. 36948234 1 102 theme diversity 242:250 arg1 mechanisms 218:227 the mechanisms 214:227 the mechanisms 214:227 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 1 102 theme diversity 242:250 arg1 events 274:279 reassortment events 261:279 reassortment events 261:279 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 1 102 theme diversity 242:250 arg1 transmission 307:318 possible interspecies transmission 285:318 possible interspecies transmission 285:318 Rotavirus group A genomic characterization is critical for understanding the mechanisms of rotavirus diversity, such as reassortment events and possible interspecies transmission. 36948234 15 103 theme rotavirus 2327:2335 arg1 monitoring 2346:2355 rotavirus genotype monitoring 2327:2355 rotavirus genotype monitoring 2327:2355 For the first time in Tanzania, we report the emergence of novel equine-like G3 and bovine-like G6 RVA strains, highlighting the importance of rotavirus genotype monitoring and genomic analysis of representative genotypes. 36948234 6 104 theme selected 929:936 arg1 genotypes 938:946 selected genotypes 929:946 selected genotypes 929:946 Whole-genome sequencing was performed on selected genotypes. 36934116 2 0 with E2 317:318 arg1 binding 356:362 reduced CD81 binding 343:362 reduced CD81 binding 343:362 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 2 0 with E2 317:318 arg1 site 403:406 an inserted N-linked glycosylation site 368:406 an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 368:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 9 1 theme vaccinia 1581:1588 arg1 infection 1600:1608 surrogate HCV vaccinia challenge infection 1567:1608 surrogate HCV vaccinia challenge infection model 1567:1614 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 7 2 theme immune 1167:1172 arg1 response 1174:1181 an improved cellular immune response 1146:1181 an improved cellular immune response 1146:1181 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 2 3 theme ectodomains 298:308 arg1 contribution 267:278 the contribution 263:278 the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 263:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 1 4 theme innate 207:212 arg1 responses 234:242 protective innate and adaptive immune responses 196:242 protective innate and adaptive immune responses 196:242 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 9 5 theme infection 1600:1608 arg1 model 1610:1614 surrogate HCV vaccinia challenge infection model 1567:1614 surrogate HCV vaccinia challenge infection model 1567:1614 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 7 6 from response 1174:1181 arg1 response 1274:1281 the neutralizing antibody response 1248:1281 the neutralizing antibody response against HCV pseudotype virus 1248:1310 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 3 7 theme mouse 640:644 arg1 model 646:650 a BALB/c mouse model 631:650 a BALB/c mouse model 631:650 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 1 8 theme adaptive 218:225 arg1 responses 234:242 protective innate and adaptive immune responses 196:242 protective innate and adaptive immune responses 196:242 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 5 9 theme mRNA-LNP 806:813 arg1 addition 790:797 the addition 786:797 the addition of sE2 mRNA-LNP for immunization 786:830 However, the addition of sE2 mRNA-LNP for immunization impaired the efficacy of the sE1 construct. 36934116 0 10 theme Hepatitis 0:8 arg1 E1 18:19 Hepatitis C virus E1 0:19 Hepatitis C virus E1 0:19 Hepatitis C virus E1 and modified E2 delivered from an mRNA vaccine induces protective immunity. 36934116 4 11 theme mouse 764:768 arg1 ovary 770:774 the mouse ovary 760:774 the mouse ovary 760:774 Vaccination with a mRNA-LNP expressing soluble E1 (sE1) significantly reduced vv/HCV titer in the mouse ovary. 36934116 7 12 from switching 1198:1206 arg1 response 1274:1281 the neutralizing antibody response 1248:1281 the neutralizing antibody response against HCV pseudotype virus 1248:1310 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 3 13 theme protective 494:503 arg1 response 512:519 a protective immune response 492:519 a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model 492:650 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 9 14 theme immunized 1636:1644 arg1 mice 1646:1649 the immunized mice 1632:1649 the immunized mice 1632:1649 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 10 15 theme sE1 1728:1730 arg1 Inclusion 1715:1723 Inclusion 1715:1723 Inclusion of sE1 with modified sE2F442NYT as mRNA-LNP vaccine candidate 1715:1785 Inclusion of sE1 with modified sE2F442NYT as mRNA-LNP vaccine candidate appeared to be beneficial for protection. 36934116 1 16 theme chronic 158:164 arg1 cases 166:170 chronic cases 158:170 chronic cases 158:170 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 8 17 theme conserved 1377:1385 arg1 epitopes 1406:1413 conserved E2 specific linear epitopes 1377:1413 conserved E2 specific linear epitopes 1377:1413 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 4 18 with Vaccination 666:676 arg1 mRNA-LNP 685:692 a mRNA-LNP 683:692 a mRNA-LNP expressing soluble E1 (sE1) 683:720 Vaccination with a mRNA-LNP expressing soluble E1 (sE1) significantly reduced vv/HCV titer in the mouse ovary. 36934116 8 19 dep vaccinated 1444:1453 arg1 E2 1441:1442 E2 1441:1442 E2 1441:1442 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 3 20 theme surrogate 524:532 arg1 VV 562:563 VV 562:563 VV 562:563 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 3 20 theme surrogate 524:532 arg1 virus 555:559 surrogate recombinant vaccinia virus 524:559 surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model 524:650 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 1 21 theme due 172:174 arg1 number 148:153 a high number 141:153 a high number of chronic cases due to an impairment of protective innate and adaptive immune responses 141:242 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 9 22 from model 1610:1614 arg1 protection 1551:1560 protection 1551:1560 protection from surrogate HCV vaccinia challenge infection model 1551:1614 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 8 23 theme specific 1390:1397 arg1 epitopes 1406:1413 conserved E2 specific linear epitopes 1377:1413 conserved E2 specific linear epitopes 1377:1413 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 7 24 theme HCV 1291:1293 arg1 virus 1306:1310 HCV pseudotype virus 1291:1310 HCV pseudotype virus 1291:1310 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 3 25 theme response 512:519 arg1 induction 479:487 The induction 475:487 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model 475:650 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 1 26 theme C 107:107 arg1 virus 109:113 Hepatitis C virus 97:113 Hepatitis C virus (HCV) 97:119 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 1 26 theme C 107:107 arg1 HCV 116:118 HCV 116:118 HCV 116:118 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 10 27 theme vaccine 1769:1775 arg1 candidate 1777:1785 mRNA-LNP vaccine candidate 1760:1785 mRNA-LNP vaccine candidate 1760:1785 Inclusion of sE1 with modified sE2F442NYT as mRNA-LNP vaccine candidate appeared to be beneficial for protection. 36934116 2 28 theme vaccine 426:432 arg1 antigen 434:440 vaccine antigen mRNA-lipid nanoparticles (LNPs) 426:472 vaccine antigen mRNA-lipid nanoparticles (LNPs) 426:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 7 29 theme neutralizing 1252:1263 arg1 response 1274:1281 the neutralizing antibody response 1248:1281 the neutralizing antibody response against HCV pseudotype virus 1248:1310 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 7 30 theme cellular 1158:1165 arg1 response 1174:1181 an improved cellular immune response 1146:1181 an improved cellular immune response 1146:1181 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 3 31 theme vaccinia 546:553 arg1 VV 562:563 VV 562:563 VV 562:563 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 3 31 theme vaccinia 546:553 arg1 virus 555:559 surrogate recombinant vaccinia virus 524:559 surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model 524:650 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 6 32 theme related 909:915 arg1 responses 926:934 Th1 related cytokine responses 905:934 Th1 related cytokine responses to the sE1 mRNA-LNP 905:954 Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. 36934116 8 33 theme modified 1432:1439 arg1 sera 1462:1465 modified E2 vaccinated animal sera 1432:1465 modified E2 vaccinated animal sera 1432:1465 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 0 34 theme mRNA 55:58 arg1 vaccine 60:66 an mRNA vaccine 52:66 an mRNA vaccine 52:66 Hepatitis C virus E1 and modified E2 delivered from an mRNA vaccine induces protective immunity. 36934116 5 35 theme sE2 802:804 arg1 mRNA-LNP 806:813 sE2 mRNA-LNP 802:813 sE2 mRNA-LNP 802:813 However, the addition of sE2 mRNA-LNP for immunization impaired the efficacy of the sE1 construct. 36934116 8 36 theme vaccinated 1444:1453 arg1 sera 1462:1465 modified E2 vaccinated animal sera 1432:1465 modified E2 vaccinated animal sera 1432:1465 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 5 37 theme construct 865:873 arg1 efficacy 845:852 the efficacy 841:852 the efficacy of the sE1 construct 841:873 However, the addition of sE2 mRNA-LNP for immunization impaired the efficacy of the sE1 construct. 36934116 10 38 with Inclusion 1715:1723 arg1 sE2F442NYT 1746:1755 modified sE2F442NYT 1737:1755 modified sE2F442NYT as mRNA-LNP vaccine candidate 1737:1785 Inclusion of sE1 with modified sE2F442NYT as mRNA-LNP vaccine candidate appeared to be beneficial for protection. 36934116 2 39 theme mRNA-lipid 442:451 arg1 LNPs 468:471 LNPs 468:471 LNPs 468:471 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 2 39 theme mRNA-lipid 442:451 arg1 nanoparticles 453:465 mRNA-lipid nanoparticles 442:465 vaccine antigen mRNA-lipid nanoparticles (LNPs) 426:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 7 40 theme mRNA-LNP 1118:1125 arg1 vaccine 1127:1133 modified sE2F442NYT nucleoside mRNA-LNP vaccine 1087:1133 modified sE2F442NYT nucleoside mRNA-LNP vaccine 1087:1133 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 9 41 theme suitable 1488:1495 arg1 model 1526:1530 a suitable immunocompetent small animal model 1486:1530 a suitable immunocompetent small animal model for HCV infection 1486:1548 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 7 42 theme sE2F442NYT 1096:1105 arg1 vaccine 1127:1133 modified sE2F442NYT nucleoside mRNA-LNP vaccine 1087:1133 modified sE2F442NYT nucleoside mRNA-LNP vaccine 1087:1133 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 1 43 theme immune 227:232 arg1 responses 234:242 protective innate and adaptive immune responses 196:242 protective innate and adaptive immune responses 196:242 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 9 44 theme small 1513:1517 arg1 model 1526:1530 a suitable immunocompetent small animal model 1486:1530 a suitable immunocompetent small animal model for HCV infection 1486:1548 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 2 45 theme E1 313:314 arg1 contribution 267:278 the contribution 263:278 the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 263:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 6 46 theme sE1 943:945 arg1 mRNA-LNP 947:954 the sE1 mRNA-LNP 939:954 the sE1 mRNA-LNP 939:954 Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. 36934116 2 47 theme reduced 343:349 arg1 binding 356:362 reduced CD81 binding 343:362 reduced CD81 binding 343:362 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 0 48 theme virus 12:16 arg1 E1 18:19 Hepatitis C virus E1 0:19 Hepatitis C virus E1 0:19 Hepatitis C virus E1 and modified E2 delivered from an mRNA vaccine induces protective immunity. 36934116 2 49 dep antigen 434:440 arg1 LNPs 468:471 LNPs 468:471 LNPs 468:471 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 2 49 dep antigen 434:440 arg1 nanoparticles 453:465 mRNA-lipid nanoparticles 442:465 vaccine antigen mRNA-lipid nanoparticles (LNPs) 426:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 3 50 theme homologous 577:586 arg1 infection 618:626 homologous HCV glycoprotein(s) challenge infection 577:626 homologous HCV glycoprotein(s) challenge infection 577:626 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 8 51 theme cross 1317:1321 arg1 reactivity 1341:1350 HCV cross genotype specific reactivity 1313:1350 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes 1313:1413 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 2 52 theme E2 335:336 arg1 contribution 267:278 the contribution 263:278 the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 263:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 9 53 theme HCV 1536:1538 arg1 infection 1540:1548 HCV infection 1536:1548 HCV infection 1536:1548 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 2 54 theme N-linked 380:387 arg1 site 403:406 an inserted N-linked glycosylation site 368:406 an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 368:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 4 55 theme vv/HCV 744:749 arg1 titer 751:755 vv/HCV titer 744:755 vv/HCV titer 744:755 Vaccination with a mRNA-LNP expressing soluble E1 (sE1) significantly reduced vv/HCV titer in the mouse ovary. 36934116 2 56 theme individual 287:296 arg1 ectodomains 298:308 the individual ectodomains 283:308 the individual ectodomains 283:308 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 7 57 theme enhanced 1209:1216 arg1 IgG 1224:1226 enhanced total IgG 1209:1226 enhanced total IgG 1209:1226 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 3 58 theme s 605:605 arg1 infection 618:626 homologous HCV glycoprotein(s) challenge infection 577:626 homologous HCV glycoprotein(s) challenge infection 577:626 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 6 59 theme co-immunization 1016:1030 arg1 presence 990:997 the presence 986:997 the presence of sE2 following co-immunization 986:1030 Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. 36934116 3 60 theme glycoprotein 592:603 arg1 infection 618:626 homologous HCV glycoprotein(s) challenge infection 577:626 homologous HCV glycoprotein(s) challenge infection 577:626 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 9 61 theme HCV 1577:1579 arg1 infection 1600:1608 surrogate HCV vaccinia challenge infection 1567:1608 surrogate HCV vaccinia challenge infection model 1567:1614 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 6 62 theme sE2 1002:1004 arg1 co-immunization 1016:1030 sE2 following co-immunization 1002:1030 sE2 following co-immunization 1002:1030 Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. 36934116 1 63 theme protective 196:205 arg1 responses 234:242 protective innate and adaptive immune responses 196:242 protective innate and adaptive immune responses 196:242 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 9 64 theme challenge 1590:1598 arg1 infection 1600:1608 surrogate HCV vaccinia challenge infection 1567:1608 surrogate HCV vaccinia challenge infection model 1567:1614 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 3 65 theme challenge 608:616 arg1 infection 618:626 homologous HCV glycoprotein(s) challenge infection 577:626 homologous HCV glycoprotein(s) challenge infection 577:626 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 8 66 theme specific 1332:1339 arg1 reactivity 1341:1350 HCV cross genotype specific reactivity 1313:1350 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes 1313:1413 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 2 67 with E2 335:336 arg1 binding 356:362 reduced CD81 binding 343:362 reduced CD81 binding 343:362 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 2 67 with E2 335:336 arg1 site 403:406 an inserted N-linked glycosylation site 368:406 an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 368:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 3 68 theme BALB/c 633:638 arg1 model 646:650 a BALB/c mouse model 631:650 a BALB/c mouse model 631:650 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 1 69 theme high 143:146 arg1 number 148:153 a high number 141:153 a high number of chronic cases due to an impairment of protective innate and adaptive immune responses 141:242 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 6 70 theme Further 876:882 arg1 analysis 884:891 Further analysis 876:891 Further analysis 876:891 Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. 36934116 9 71 located observed 1620:1627 arg1 mice 1646:1649 the immunized mice 1632:1649 the immunized mice 1632:1649 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 9 71 located observed 1620:1627 arg2 protection 1551:1560 protection 1551:1560 protection from surrogate HCV vaccinia challenge infection model 1551:1614 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 8 72 theme E2 1387:1388 arg1 epitopes 1406:1413 conserved E2 specific linear epitopes 1377:1413 conserved E2 specific linear epitopes 1377:1413 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 1 73 theme cases 166:170 arg1 number 148:153 a high number 141:153 a high number of chronic cases due to an impairment of protective innate and adaptive immune responses 141:242 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 8 74 theme linear 1399:1404 arg1 epitopes 1406:1413 conserved E2 specific linear epitopes 1377:1413 conserved E2 specific linear epitopes 1377:1413 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 7 75 theme vaccine 1127:1133 arg1 use 1080:1082 the use 1076:1082 the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine 1076:1133 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 3 76 theme immune 505:510 arg1 response 512:519 a protective immune response 492:519 a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model 492:650 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 1 77 theme Hepatitis 97:105 arg1 virus 109:113 Hepatitis C virus 97:113 Hepatitis C virus (HCV) 97:119 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 1 77 theme Hepatitis 97:105 arg1 HCV 116:118 HCV 116:118 HCV 116:118 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 7 78 theme pseudotype 1295:1304 arg1 virus 1306:1310 HCV pseudotype virus 1291:1310 HCV pseudotype virus 1291:1310 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 7 79 theme improved 1149:1156 arg1 response 1174:1181 an improved cellular immune response 1146:1181 an improved cellular immune response 1146:1181 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 3 80 theme recombinant 534:544 arg1 VV 562:563 VV 562:563 VV 562:563 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 3 80 theme recombinant 534:544 arg1 virus 555:559 surrogate recombinant vaccinia virus 524:559 surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model 524:650 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 6 81 theme cytokine 917:924 arg1 responses 926:934 Th1 related cytokine responses 905:934 Th1 related cytokine responses to the sE1 mRNA-LNP 905:954 Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. 36934116 9 82 theme unmodified 1682:1691 arg1 sE2 1693:1695 an unmodified sE2 1679:1695 an unmodified sE2 1679:1695 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 2 83 from binding 356:362 arg1 combination 411:421 combination 411:421 combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 411:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 7 84 theme antibody 1265:1272 arg1 response 1274:1281 the neutralizing antibody response 1248:1281 the neutralizing antibody response against HCV pseudotype virus 1248:1310 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 9 85 dep model 1526:1530 arg1 absence 1475:1481 absence 1475:1481 absence 1475:1481 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 9 85 dep model 1526:1530 arg1 the 1471:1473 the 1471:1473 the 1471:1473 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 6 86 theme Th1 905:907 arg1 responses 926:934 Th1 related cytokine responses 905:934 Th1 related cytokine responses to the sE1 mRNA-LNP 905:954 Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. 36934116 9 87 theme mRNA-LNP 1697:1704 arg1 vaccine 1706:1712 mRNA-LNP vaccine 1697:1712 mRNA-LNP vaccine 1697:1712 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 8 88 theme animal 1455:1460 arg1 sera 1462:1465 modified E2 vaccinated animal sera 1432:1465 modified E2 vaccinated animal sera 1432:1465 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 0 89 theme protective 76:85 arg1 immunity 87:94 protective immunity 76:94 protective immunity 76:94 Hepatitis C virus E1 and modified E2 delivered from an mRNA vaccine induces protective immunity. 36934116 5 90 theme sE1 861:863 arg1 construct 865:873 the sE1 construct 857:873 the sE1 construct 857:873 However, the addition of sE2 mRNA-LNP for immunization impaired the efficacy of the sE1 construct. 36934116 10 91 theme mRNA-LNP 1760:1767 arg1 candidate 1777:1785 mRNA-LNP vaccine candidate 1760:1785 mRNA-LNP vaccine candidate 1760:1785 Inclusion of sE1 with modified sE2F442NYT as mRNA-LNP vaccine candidate appeared to be beneficial for protection. 36934116 7 92 theme nucleoside 1107:1116 arg1 vaccine 1127:1133 modified sE2F442NYT nucleoside mRNA-LNP vaccine 1087:1133 modified sE2F442NYT nucleoside mRNA-LNP vaccine 1087:1133 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 2 93 from site 403:406 arg1 combination 411:421 combination 411:421 combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 411:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 2 94 link N-linked 380:387 arg1 site 403:406 an inserted N-linked glycosylation site 368:406 an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 368:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 0 95 theme C 10:10 arg1 E1 18:19 Hepatitis C virus E1 0:19 Hepatitis C virus E1 0:19 Hepatitis C virus E1 and modified E2 delivered from an mRNA vaccine induces protective immunity. 36934116 9 96 theme immunocompetent 1497:1511 arg1 model 1526:1530 a suitable immunocompetent small animal model 1486:1530 a suitable immunocompetent small animal model for HCV infection 1486:1548 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 2 97 theme E2 317:318 arg1 contribution 267:278 the contribution 263:278 the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 263:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 1 98 theme responses 234:242 arg1 impairment 182:191 an impairment 179:191 an impairment of protective innate and adaptive immune responses 179:242 Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. 36934116 9 99 theme animal 1519:1524 arg1 model 1526:1530 a suitable immunocompetent small animal model 1486:1530 a suitable immunocompetent small animal model for HCV infection 1486:1548 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 2 100 theme CD81 351:354 arg1 binding 356:362 reduced CD81 binding 343:362 reduced CD81 binding 343:362 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 9 101 dep sE1 1666:1668 arg1 vaccine 1706:1712 mRNA-LNP vaccine 1697:1712 mRNA-LNP vaccine 1697:1712 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 0 102 theme modified 25:32 arg1 E2 34:35 modified E2 25:35 modified E2 25:35 Hepatitis C virus E1 and modified E2 delivered from an mRNA vaccine induces protective immunity. 36934116 2 103 gly glycosylation 389:401 arg2 site 403:406 an inserted N-linked glycosylation site 368:406 an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 368:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 7 104 theme total 1218:1222 arg1 IgG 1224:1226 enhanced total IgG 1209:1226 enhanced total IgG 1209:1226 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 2 105 theme glycosylation 389:401 arg1 site 403:406 an inserted N-linked glycosylation site 368:406 an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 368:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 8 106 theme HCV 1313:1315 arg1 reactivity 1341:1350 HCV cross genotype specific reactivity 1313:1350 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes 1313:1413 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 2 107 theme modified 326:333 arg1 E2 335:336 a modified E2 324:336 a modified E2 324:336 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 7 108 theme immunogenicity 1047:1060 arg1 Evaluation 1033:1042 Evaluation 1033:1042 Evaluation of immunogenicity 1033:1060 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 7 109 from IgG 1224:1226 arg1 response 1274:1281 the neutralizing antibody response 1248:1281 the neutralizing antibody response against HCV pseudotype virus 1248:1310 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 2 110 theme inserted 371:378 arg1 site 403:406 an inserted N-linked glycosylation site 368:406 an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 368:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 8 111 theme genotype 1323:1330 arg1 reactivity 1341:1350 HCV cross genotype specific reactivity 1313:1350 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes 1313:1413 HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. 36934116 10 112 theme modified 1737:1744 arg1 sE2F442NYT 1746:1755 modified sE2F442NYT 1737:1755 modified sE2F442NYT as mRNA-LNP vaccine candidate 1737:1785 Inclusion of sE1 with modified sE2F442NYT as mRNA-LNP vaccine candidate appeared to be beneficial for protection. 36934116 7 113 theme isotype 1190:1196 arg1 switching 1198:1206 IgG2a isotype switching 1184:1206 IgG2a isotype switching 1184:1206 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 3 114 theme HCV 588:590 arg1 infection 618:626 homologous HCV glycoprotein(s) challenge infection 577:626 homologous HCV glycoprotein(s) challenge infection 577:626 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 4 115 theme soluble 705:711 arg1 sE1 717:719 sE1 717:719 sE1 717:719 Vaccination with a mRNA-LNP expressing soluble E1 (sE1) significantly reduced vv/HCV titer in the mouse ovary. 36934116 4 115 theme soluble 705:711 arg1 E1 713:714 soluble E1 705:714 soluble E1 (sE1) 705:720 Vaccination with a mRNA-LNP expressing soluble E1 (sE1) significantly reduced vv/HCV titer in the mouse ovary. 36934116 7 116 theme IgG2a 1184:1188 arg1 switching 1198:1206 IgG2a isotype switching 1184:1206 IgG2a isotype switching 1184:1206 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 2 117 with E1 313:314 arg1 binding 356:362 reduced CD81 binding 343:362 reduced CD81 binding 343:362 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 2 117 with E1 313:314 arg1 site 403:406 an inserted N-linked glycosylation site 368:406 an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs) 368:472 Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). 36934116 9 118 theme surrogate 1567:1575 arg1 infection 1600:1608 surrogate HCV vaccinia challenge infection 1567:1608 surrogate HCV vaccinia challenge infection model 1567:1614 In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. 36934116 7 119 from increase 1236:1243 arg1 response 1274:1281 the neutralizing antibody response 1248:1281 the neutralizing antibody response against HCV pseudotype virus 1248:1310 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36934116 6 120 theme following 1006:1014 arg1 co-immunization 1016:1030 sE2 following co-immunization 1002:1030 sE2 following co-immunization 1002:1030 Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. 36934116 3 121 gly glycoprotein 592:603 arg1 glycoprotein 592:603 homologous HCV glycoprotein(s) challenge infection 577:626 homologous HCV glycoprotein(s) challenge infection 577:626 The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. 36934116 7 122 theme modified 1087:1094 arg1 vaccine 1127:1133 modified sE2F442NYT nucleoside mRNA-LNP vaccine 1087:1133 modified sE2F442NYT nucleoside mRNA-LNP vaccine 1087:1133 Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. 36334264 8 0 theme mutation 1026:1033 arg1 effect 1012:1017 the effect 1008:1017 the effect of the mutation 1008:1033 A cell experiment was conducted to explore the effect of the mutation. 36334264 13 1 theme Sanger 1730:1735 arg1 sequencing 1737:1746 Sanger sequencing 1730:1746 Sanger sequencing 1730:1746 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 2 2 theme hypophosphatemic 346:361 arg1 type 371:374 autosomal recessive hypophosphatemic rickets type 1 326:376 autosomal recessive hypophosphatemic rickets type 1 (ARHR1) 326:384 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 2 2 theme hypophosphatemic 346:361 arg1 ARHR1 379:383 ARHR1 379:383 ARHR1 379:383 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 7 3 theme Cytoscan 855:862 arg1 array 867:871 Cytoscan HD array 855:871 Cytoscan HD array 855:871 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 9 4 theme 4-year-old 1061:1070 arg1 boy 1072:1074 a 4-year-old boy 1059:1074 a 4-year-old boy 1059:1074 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 9 4 theme 4-year-old 1061:1070 arg1 proband 1048:1054 The proband 1044:1054 The proband 1044:1054 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 1 5 theme genetic 263:269 arg1 analysis 271:278 genetic analysis 263:278 genetic analysis 263:278 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 15 6 theme DSPP 1986:1989 arg1 mutations 1991:1999 DSPP mutations 1986:1999 DSPP mutations 1986:1999 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 15 7 from patient 2019:2025 arg1 absent 2005:2010 absent 2005:2010 absent 2005:2010 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 15 8 theme dentinogenesis 1944:1957 arg1 DGI 1971:1973 DGI 1971:1973 DGI 1971:1973 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 15 8 theme dentinogenesis 1944:1957 arg1 imperfecta 1959:1968 dentinogenesis imperfecta 1944:1968 dentinogenesis imperfecta (DGI) 1944:1974 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 16 9 theme novel 2221:2225 arg1 mutation 2239:2246 a novel start codon mutation 2219:2246 a novel start codon mutation (c.1A > T, p.Met1Leu) 2219:2268 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 15 10 theme his 2031:2033 arg1 mother 2035:2040 his mother 2031:2040 his mother 2031:2040 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 16 11 with patient 2283:2289 arg1 ARHR1 2296:2300 ARHR1 2296:2300 ARHR1 2296:2300 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 5 12 theme Chinese 765:771 arg1 patient 773:779 a Chinese patient 763:779 a Chinese patient with HR 763:787 METHODS We report the clinical features of a Chinese patient with HR. 36334264 12 13 theme large 1404:1408 arg1 deletion 1410:1417 a large deletion 1402:1417 a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE 1402:1551 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 2 14 theme reported 486:493 arg1 patients 495:502 only 30 reported patients 478:502 only 30 reported patients 478:502 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 15 15 theme dentin 1919:1924 arg1 dysplasia 1926:1934 dentin dysplasia 1919:1934 dentin dysplasia (DD) 1919:1939 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 15 15 theme dentin 1919:1924 arg1 DD 1937:1938 DD 1937:1938 DD 1937:1938 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 16 16 theme large 2200:2204 arg1 deletion 2206:2213 a large deletion 2198:2213 a large deletion 2198:2213 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 8 17 theme cell 967:970 arg1 experiment 972:981 A cell experiment 965:981 A cell experiment 965:981 A cell experiment was conducted to explore the effect of the mutation. 36334264 7 18 theme quantitative 905:916 arg1 PCR 918:920 genomic quantitative PCR 897:920 genomic quantitative PCR (qPCR) 897:927 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 7 18 theme quantitative 905:916 arg1 qPCR 923:926 qPCR 923:926 qPCR 923:926 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 1 19 theme Hereditary 124:133 arg1 HR 161:162 HR 161:162 HR 161:162 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 1 19 theme Hereditary 124:133 arg1 rickets 152:158 CONTEXT Hereditary hypophosphatemic rickets 116:158 CONTEXT Hereditary hypophosphatemic rickets (HR) 116:163 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 16 20 dep mutation 2239:2246 arg1 T 2256:2256 c.1A > T 2249:2256 c.1A > T 2249:2256 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 16 20 dep mutation 2239:2246 arg1 p.Met1Leu 2259:2267 p.Met1Leu 2259:2267 p.Met1Leu 2259:2267 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 3 21 theme DMP1 564:567 arg1 mutations 569:577 compound heterozygous DMP1 mutations 542:577 compound heterozygous DMP1 mutations 542:577 To date, there has been no case with compound heterozygous DMP1 mutations. 36334264 12 22 theme c.1A 1369:1372 arg1 p.Met1Leu 1379:1387 p.Met1Leu 1379:1387 p.Met1Leu 1379:1387 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 12 22 theme c.1A 1369:1372 arg1 T 1376:1376 c.1A > T 1369:1376 c.1A > T 1369:1376 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 13 23 with expression 1635:1644 arg1 weight 1685:1690 smaller molecular weight 1667:1690 smaller molecular weight 1667:1690 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 13 23 with expression 1635:1644 arg1 defect 1705:1710 cleavage defect 1696:1710 cleavage defect 1696:1710 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 3 24 theme compound 542:549 arg1 mutations 569:577 compound heterozygous DMP1 mutations 542:577 compound heterozygous DMP1 mutations 542:577 To date, there has been no case with compound heterozygous DMP1 mutations. 36334264 4 25 theme DMP1 645:648 arg1 mutations 632:640 the first compound heterozygous mutations 600:640 the first compound heterozygous mutations of DMP1 causing ARHR1 600:662 OBJECTIVE To report the first compound heterozygous mutations of DMP1 causing ARHR1 and confirm the effect of the mutation on DMP1 protein. 36334264 0 26 theme Recessive 73:81 arg1 Rickets 100:106 Rare Autosomal Recessive Hypophosphatemic Rickets 58:106 Rare Autosomal Recessive Hypophosphatemic Rickets Type 1 58:113 The First Compound Heterozygous Mutations of DMP1 Causing Rare Autosomal Recessive Hypophosphatemic Rickets Type 1. 36334264 9 27 theme year 1136:1139 arg1 age 1130:1132 age 1130:1132 age 1 year 1130:1139 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 12 28 theme start 1347:1351 arg1 mutation 1359:1366 a novel start codon mutation 1339:1366 a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 1339:1396 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 13 29 theme molecular 1675:1683 arg1 weight 1685:1690 smaller molecular weight 1667:1690 smaller molecular weight 1667:1690 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 9 30 theme tooth 1145:1149 arg1 loss 1151:1154 tooth loss 1145:1154 tooth loss 1145:1154 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 9 31 from years 1184:1188 arg1 hit 1169:1171 a mild hit 1162:1171 a mild hit at age 3.5 years 1162:1188 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 7 32 theme HD 864:865 arg1 array 867:871 Cytoscan HD array 855:871 Cytoscan HD array 855:871 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 12 33 theme integrin-binding 1447:1462 arg1 gene 1510:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 12 34 gly glycoprotein 1480:1491 arg1 glycoprotein 1480:1491 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 11 35 theme Family 1272:1277 arg1 history 1279:1285 Family history 1272:1285 Family history 1272:1285 Family history was negative. 36334264 3 36 with case 532:535 arg1 mutations 569:577 compound heterozygous DMP1 mutations 542:577 compound heterozygous DMP1 mutations 542:577 To date, there has been no case with compound heterozygous DMP1 mutations. 36334264 12 37 from mutation 1359:1366 arg1 DMP1 1393:1396 DMP1 1393:1396 DMP1 1393:1396 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 0 38 dep Rickets 100:106 arg1 Type 108:111 Type 1 108:113 Rare Autosomal Recessive Hypophosphatemic Rickets Type 1 58:113 The First Compound Heterozygous Mutations of DMP1 Causing Rare Autosomal Recessive Hypophosphatemic Rickets Type 1. 36334264 12 39 theme N-linked 1471:1478 arg1 gene 1510:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 15 40 from mother 2035:2040 arg1 absent 2005:2010 absent 2005:2010 absent 2005:2010 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 2 41 theme matrix 429:434 arg1 protein 436:442 dentin matrix protein 1 422:444 dentin matrix protein 1 (DMP1) 422:451 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 2 41 theme matrix 429:434 arg1 DMP1 447:450 DMP1 447:450 DMP1 447:450 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 14 42 theme long-range 1864:1873 arg1 PCR 1875:1877 long-range PCR 1864:1877 long-range PCR 1864:1877 The maternally inherited deletion was validated by Cytoscan and qPCR, and the breakpoint was finally identified by long-range PCR and Sanger sequencing. 36334264 13 43 theme DMP1 1649:1652 arg1 protein 1654:1660 DMP1 protein 1649:1660 DMP1 protein 1649:1660 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 5 44 theme clinical 742:749 arg1 features 751:758 the clinical features 738:758 the clinical features of a Chinese patient with HR 738:787 METHODS We report the clinical features of a Chinese patient with HR. 36334264 9 45 theme mild 1164:1167 arg1 hit 1169:1171 a mild hit 1162:1171 a mild hit at age 3.5 years 1162:1188 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 4 46 from effect 680:685 arg1 protein 711:717 DMP1 protein 706:717 DMP1 protein 706:717 OBJECTIVE To report the first compound heterozygous mutations of DMP1 causing ARHR1 and confirm the effect of the mutation on DMP1 protein. 36334264 16 47 theme codon 2233:2237 arg1 mutation 2239:2246 a novel start codon mutation 2219:2246 a novel start codon mutation (c.1A > T, p.Met1Leu) 2219:2268 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 5 48 with patient 773:779 arg1 HR 786:787 HR 786:787 HR 786:787 METHODS We report the clinical features of a Chinese patient with HR. 36334264 2 49 theme homozygous 399:408 arg1 mutation 410:417 a homozygous mutation 397:417 a homozygous mutation of dentin matrix protein 1 (DMP1) 397:451 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 12 50 dep mutation 1359:1366 arg1 p.Met1Leu 1379:1387 p.Met1Leu 1379:1387 p.Met1Leu 1379:1387 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 12 50 dep mutation 1359:1366 arg1 T 1376:1376 c.1A > T 1369:1376 c.1A > T 1369:1376 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 1 51 theme differential 290:301 arg1 diagnosis 303:311 a differential diagnosis 288:311 a differential diagnosis 288:311 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 12 52 theme novel 1341:1345 arg1 mutation 1359:1366 a novel start codon mutation 1339:1366 a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 1339:1396 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 2 53 theme recessive 336:344 arg1 type 371:374 autosomal recessive hypophosphatemic rickets type 1 326:376 autosomal recessive hypophosphatemic rickets type 1 (ARHR1) 326:384 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 2 53 theme recessive 336:344 arg1 ARHR1 379:383 ARHR1 379:383 ARHR1 379:383 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 0 54 theme DMP1 45:48 arg1 Mutations 32:40 The First Compound Heterozygous Mutations 0:40 The First Compound Heterozygous Mutations of DMP1 0:48 The First Compound Heterozygous Mutations of DMP1 Causing Rare Autosomal Recessive Hypophosphatemic Rickets Type 1. 36334264 16 55 theme c.1A 2249:2252 arg1 T 2256:2256 c.1A > T 2249:2256 c.1A > T 2249:2256 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 16 55 theme c.1A 2249:2252 arg1 p.Met1Leu 2259:2267 p.Met1Leu 2259:2267 p.Met1Leu 2259:2267 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 4 56 dep first 604:608 arg1 heterozygous 619:630 heterozygous 619:630 heterozygous 619:630 OBJECTIVE To report the first compound heterozygous mutations of DMP1 causing ARHR1 and confirm the effect of the mutation on DMP1 protein. 36334264 13 57 theme inherited 1575:1583 arg1 mutation 1597:1604 The novel paternally inherited start codon mutation 1554:1604 The novel paternally inherited start codon mutation 1554:1604 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 16 58 theme heterozygous 2156:2167 arg1 mutations 2174:2182 compound heterozygous DMP1 mutations 2147:2182 compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) 2147:2268 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 1 59 theme different 235:243 arg1 genes 245:249 different genes 235:249 different genes 235:249 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 15 60 dep patient 2019:2025 arg1 the 2015:2017 the 2015:2017 the 2015:2017 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 13 61 theme codon 1591:1595 arg1 mutation 1597:1604 The novel paternally inherited start codon mutation 1554:1604 The novel paternally inherited start codon mutation 1554:1604 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 12 62 link N-linked 1471:1478 arg1 gene 1510:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 2 63 theme rickets 363:369 arg1 type 371:374 autosomal recessive hypophosphatemic rickets type 1 326:376 autosomal recessive hypophosphatemic rickets type 1 (ARHR1) 326:384 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 2 63 theme rickets 363:369 arg1 ARHR1 379:383 ARHR1 379:383 ARHR1 379:383 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 15 64 from absent 2005:2010 arg1 patient 2019:2025 patient 2019:2025 patient 2019:2025 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 15 64 from absent 2005:2010 arg1 mother 2035:2040 his mother 2031:2040 his mother 2031:2040 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 10 65 theme biochemical 1213:1223 arg1 measurement 1225:1235 biochemical measurement 1213:1235 biochemical measurement 1213:1235 Physical examination, biochemical measurement, and imaging finding indicated HR. 36334264 13 66 theme novel 1558:1562 arg1 mutation 1597:1604 The novel paternally inherited start codon mutation 1554:1604 The novel paternally inherited start codon mutation 1554:1604 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 16 67 theme start 2227:2231 arg1 mutation 2239:2246 a novel start codon mutation 2219:2246 a novel start codon mutation (c.1A > T, p.Met1Leu) 2219:2268 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 10 68 theme imaging 1242:1248 arg1 finding 1250:1256 imaging finding 1242:1256 imaging finding 1242:1256 Physical examination, biochemical measurement, and imaging finding indicated HR. 36334264 5 69 dep METHODS 720:726 arg1 report 731:736 report 731:736 report the clinical features of a Chinese patient with HR 731:787 METHODS We report the clinical features of a Chinese patient with HR. 36334264 4 70 theme first 604:608 arg1 mutations 632:640 the first compound heterozygous mutations 600:640 the first compound heterozygous mutations of DMP1 causing ARHR1 600:662 OBJECTIVE To report the first compound heterozygous mutations of DMP1 causing ARHR1 and confirm the effect of the mutation on DMP1 protein. 36334264 9 71 theme genu 1091:1094 arg1 varum 1096:1100 genu varum 1091:1100 genu varum 1091:1100 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 1 72 theme inherited 188:196 arg1 hypophosphatemia 198:213 inherited hypophosphatemia 188:213 inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis 188:311 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 5 73 theme patient 773:779 arg1 features 751:758 the clinical features 738:758 the clinical features of a Chinese patient with HR 738:787 METHODS We report the clinical features of a Chinese patient with HR. 36334264 1 74 theme CONTEXT 116:122 arg1 HR 161:162 HR 161:162 HR 161:162 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 1 74 theme CONTEXT 116:122 arg1 rickets 152:158 CONTEXT Hereditary hypophosphatemic rickets 116:158 CONTEXT Hereditary hypophosphatemic rickets (HR) 116:163 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 7 75 used used 934:937 arg2 qPCR 923:926 qPCR 923:926 qPCR 923:926 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 7 75 used used 934:937 arg2 sequencing 881:890 Sanger sequencing 874:890 Sanger sequencing 874:890 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 7 75 used used 934:937 arg2 array 867:871 Cytoscan HD array 855:871 Cytoscan HD array 855:871 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 7 75 used used 934:937 arg2 PCR 918:920 genomic quantitative PCR 897:920 genomic quantitative PCR (qPCR) 897:927 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 3 76 theme heterozygous 551:562 arg1 mutations 569:577 compound heterozygous DMP1 mutations 542:577 compound heterozygous DMP1 mutations 542:577 To date, there has been no case with compound heterozygous DMP1 mutations. 36334264 1 77 theme hypophosphatemic 135:150 arg1 HR 161:162 HR 161:162 HR 161:162 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 1 77 theme hypophosphatemic 135:150 arg1 rickets 152:158 CONTEXT Hereditary hypophosphatemic rickets 116:158 CONTEXT Hereditary hypophosphatemic rickets (HR) 116:163 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 12 78 theme family 1503:1508 arg1 gene 1510:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 12 79 theme > 1374:1374 arg1 p.Met1Leu 1379:1387 p.Met1Leu 1379:1387 p.Met1Leu 1379:1387 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 12 79 theme > 1374:1374 arg1 T 1376:1376 c.1A > T 1369:1376 c.1A > T 1369:1376 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 13 80 theme cleavage 1696:1703 arg1 defect 1705:1710 cleavage defect 1696:1710 cleavage defect 1696:1710 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 7 81 theme genomic 897:903 arg1 PCR 918:920 genomic quantitative PCR 897:920 genomic quantitative PCR (qPCR) 897:927 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 7 81 theme genomic 897:903 arg1 qPCR 923:926 qPCR 923:926 qPCR 923:926 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 16 82 theme Chinese 2275:2281 arg1 patient 2283:2289 a Chinese patient 2273:2289 a Chinese patient with ARHR1 2273:2300 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 13 83 theme protein 1654:1660 arg1 expression 1635:1644 decreased expression 1625:1644 decreased expression of DMP1 protein with smaller molecular weight and cleavage defect 1625:1710 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 0 84 theme Hypophosphatemic 83:98 arg1 Rickets 100:106 Rare Autosomal Recessive Hypophosphatemic Rickets 58:106 Rare Autosomal Recessive Hypophosphatemic Rickets Type 1 58:113 The First Compound Heterozygous Mutations of DMP1 Causing Rare Autosomal Recessive Hypophosphatemic Rickets Type 1. 36334264 9 85 theme 1 1134:1134 arg1 year 1136:1139 year 1136:1139 year 1136:1139 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 15 86 theme dysplasia 1926:1934 arg1 Manifestation 1902:1914 Manifestation 1902:1914 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations 1902:1999 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 15 87 theme imperfecta 1959:1968 arg1 Manifestation 1902:1914 Manifestation 1902:1914 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations 1902:1999 Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. 36334264 12 88 theme glycoprotein 1480:1491 arg1 gene 1510:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 12 89 theme codon 1353:1357 arg1 mutation 1359:1366 a novel start codon mutation 1339:1366 a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 1339:1396 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 13 90 theme smaller 1667:1673 arg1 weight 1685:1690 smaller molecular weight 1667:1690 smaller molecular weight 1667:1690 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 7 91 theme Sanger 874:879 arg1 sequencing 881:890 Sanger sequencing 874:890 Sanger sequencing 874:890 Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. 36334264 12 92 theme SIBLING 1494:1500 arg1 gene 1510:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 16 93 theme DMP1 2169:2172 arg1 mutations 2174:2182 compound heterozygous DMP1 mutations 2147:2182 compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) 2147:2268 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 14 94 theme Sanger 1883:1888 arg1 sequencing 1890:1899 Sanger sequencing 1883:1899 Sanger sequencing 1883:1899 The maternally inherited deletion was validated by Cytoscan and qPCR, and the breakpoint was finally identified by long-range PCR and Sanger sequencing. 36334264 4 95 theme mutation 694:701 arg1 effect 680:685 the effect 676:685 the effect of the mutation on DMP1 protein 676:717 OBJECTIVE To report the first compound heterozygous mutations of DMP1 causing ARHR1 and confirm the effect of the mutation on DMP1 protein. 36334264 13 96 theme decreased 1625:1633 arg1 expression 1635:1644 decreased expression 1625:1644 decreased expression of DMP1 protein with smaller molecular weight and cleavage defect 1625:1710 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 1 97 theme hypophosphatemia 198:213 arg1 group 179:183 a group 177:183 a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis 177:311 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 1 97 theme hypophosphatemia 198:213 arg1 hypophosphatemia 198:213 inherited hypophosphatemia 188:213 inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis 188:311 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 36334264 12 98 theme small 1441:1445 arg1 gene 1510:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 4 99 theme DMP1 706:709 arg1 protein 711:717 DMP1 protein 706:717 DMP1 protein 706:717 OBJECTIVE To report the first compound heterozygous mutations of DMP1 causing ARHR1 and confirm the effect of the mutation on DMP1 protein. 36334264 0 100 theme First 4:8 arg1 Mutations 32:40 The First Compound Heterozygous Mutations 0:40 The First Compound Heterozygous Mutations of DMP1 0:48 The First Compound Heterozygous Mutations of DMP1 Causing Rare Autosomal Recessive Hypophosphatemic Rickets Type 1. 36334264 2 101 with rare 467:470 arg1 patients 495:502 only 30 reported patients 478:502 only 30 reported patients 478:502 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 12 102 theme ligand 1464:1469 arg1 gene 1510:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene 1437:1513 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 2 103 theme dentin 422:427 arg1 protein 436:442 dentin matrix protein 1 422:444 dentin matrix protein 1 (DMP1) 422:451 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 2 103 theme dentin 422:427 arg1 DMP1 447:450 DMP1 447:450 DMP1 447:450 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 12 104 from deletion 1410:1417 arg1 DMP1 1393:1396 DMP1 1393:1396 DMP1 1393:1396 WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. 36334264 16 105 dep CONCLUSION 2107:2116 arg1 report 2121:2126 report 2121:2126 report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1 2121:2300 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 14 106 theme inherited 1764:1772 arg1 deletion 1774:1781 The maternally inherited deletion 1749:1781 The maternally inherited deletion 1749:1781 The maternally inherited deletion was validated by Cytoscan and qPCR, and the breakpoint was finally identified by long-range PCR and Sanger sequencing. 36334264 9 107 theme age 1176:1178 arg1 years 1184:1188 age 3.5 years 1176:1188 age 3.5 years 1176:1188 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 6 108 theme Whole-exome 790:800 arg1 WES 814:816 WES 814:816 WES 814:816 Whole-exome sequencing (WES) was performed on the proband. 36334264 6 108 theme Whole-exome 790:800 arg1 sequencing 802:811 Whole-exome sequencing 790:811 Whole-exome sequencing (WES) 790:817 Whole-exome sequencing (WES) was performed on the proband. 36334264 9 109 dep RESULTS 1036:1042 arg1 boy 1072:1074 a 4-year-old boy 1059:1074 a 4-year-old boy 1059:1074 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 9 109 dep RESULTS 1036:1042 arg1 proband 1048:1054 The proband 1044:1054 The proband 1044:1054 RESULTS The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. 36334264 16 110 theme first 2136:2140 arg1 time 2142:2145 the first time 2132:2145 the first time 2132:2145 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 2 111 theme protein 436:442 arg1 mutation 410:417 a homozygous mutation 397:417 a homozygous mutation of dentin matrix protein 1 (DMP1) 397:451 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 16 112 theme compound 2147:2154 arg1 mutations 2174:2182 compound heterozygous DMP1 mutations 2147:2182 compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) 2147:2268 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 2 113 theme autosomal 326:334 arg1 type 371:374 autosomal recessive hypophosphatemic rickets type 1 326:376 autosomal recessive hypophosphatemic rickets type 1 (ARHR1) 326:384 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 2 113 theme autosomal 326:334 arg1 ARHR1 379:383 ARHR1 379:383 ARHR1 379:383 Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. 36334264 16 114 theme > 2254:2254 arg1 T 2256:2256 c.1A > T 2249:2256 c.1A > T 2249:2256 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 16 114 theme > 2254:2254 arg1 p.Met1Leu 2259:2267 p.Met1Leu 2259:2267 p.Met1Leu 2259:2267 CONCLUSION We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1. 36334264 10 115 theme Physical 1191:1198 arg1 examination 1200:1210 Physical examination 1191:1210 Physical examination 1191:1210 Physical examination, biochemical measurement, and imaging finding indicated HR. 36334264 0 116 dep First 4:8 arg1 Heterozygous 19:30 Heterozygous 19:30 Heterozygous 19:30 The First Compound Heterozygous Mutations of DMP1 Causing Rare Autosomal Recessive Hypophosphatemic Rickets Type 1. 36334264 13 117 theme start 1585:1589 arg1 mutation 1597:1604 The novel paternally inherited start codon mutation 1554:1604 The novel paternally inherited start codon mutation 1554:1604 The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. 36334264 1 118 theme genes 245:249 arg1 mutations 222:230 mutations 222:230 mutations of different genes, which need genetic analysis to make a differential diagnosis 222:311 CONTEXT Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. 35132228 0 0 theme exchange 86:93 arg1 MRI 115:117 mannose-weighted chemical exchange saturation transfer MRI 60:117 mannose-weighted chemical exchange saturation transfer MRI 60:117 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 3 1 link N-linked 540:547 arg1 biomarker 629:637 a biomarker 627:637 a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 627:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 3 1 link N-linked 540:547 arg1 glycans 549:555 high-mannose N-linked glycans 527:555 high-mannose N-linked glycans 527:555 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 3 2 theme chemical 709:716 arg1 resonance 763:771 chemical exchange saturation transfer (CEST) magnetic resonance 709:771 mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 692:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 1 3 theme biodistribution 148:162 arg1 tracking 124:131 The tracking 120:131 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) 120:218 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 4 4 from increases 945:953 arg1 signal 971:976 the CEST MRI signal 958:976 the CEST MRI signal 958:976 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 0 5 theme chemical 77:84 arg1 MRI 115:117 mannose-weighted chemical exchange saturation transfer MRI 60:117 mannose-weighted chemical exchange saturation transfer MRI 60:117 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 6 6 theme label-free 1255:1264 arg1 imaging 1266:1272 The label-free imaging 1251:1272 The label-free imaging of hMSCs 1251:1281 The label-free imaging of hMSCs may facilitate the development and testing of cell therapies. 35132228 3 7 theme hMSCs 607:611 arg1 surface 596:602 the surface 592:602 the surface of hMSCs 592:611 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 4 8 theme hMSCs 1046:1050 arg1 intensity 1026:1034 the bioluminescence intensity 1006:1034 the bioluminescence intensity of viable hMSCs for 14 days 1006:1062 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 5 9 theme MRI 1170:1172 arg1 intensities 1181:1191 lower CEST MRI signal intensities 1159:1191 lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose 1159:1248 In vitro, osteogenically differentiated hMSCs led to lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose. 35132228 0 10 theme transfer 106:113 arg1 MRI 115:117 mannose-weighted chemical exchange saturation transfer MRI 60:117 mannose-weighted chemical exchange saturation transfer MRI 60:117 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 4 11 theme viable 1039:1044 arg1 hMSCs 1046:1050 viable hMSCs 1039:1050 viable hMSCs 1039:1050 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 4 12 theme CEST 962:965 arg1 signal 971:976 the CEST MRI signal 958:976 the CEST MRI signal 958:976 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 0 13 theme saturation 95:104 arg1 MRI 115:117 mannose-weighted chemical exchange saturation transfer MRI 60:117 mannose-weighted chemical exchange saturation transfer MRI 60:117 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 3 14 theme hMSCs 683:687 arg1 tracking 658:665 the label-free tracking 643:665 the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 643:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 5 15 theme differentiated 1131:1144 arg1 hMSCs 1146:1150 osteogenically differentiated hMSCs 1116:1150 osteogenically differentiated hMSCs 1116:1150 In vitro, osteogenically differentiated hMSCs led to lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose. 35132228 4 16 theme mannose 1097:1103 arg1 presence 1085:1092 the presence 1081:1092 the presence of mannose 1081:1103 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 6 17 theme cell 1329:1332 arg1 therapies 1334:1342 cell therapies 1329:1342 cell therapies 1329:1342 The label-free imaging of hMSCs may facilitate the development and testing of cell therapies. 35132228 2 18 theme regulatory 376:385 arg1 processes 387:395 bespoke manufacturing and regulatory processes 350:395 bespoke manufacturing and regulatory processes 350:395 However, reporter genes and exogenous labels may require bespoke manufacturing and regulatory processes if used in cell therapies, and the labels may alter the cells' properties and are diluted on cellular division. 35132228 1 19 theme transplanted 167:178 arg1 hMSCs 213:217 hMSCs 213:217 hMSCs 213:217 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 1 19 theme transplanted 167:178 arg1 cells 206:210 transplanted human mesenchymal stromal cells 167:210 transplanted human mesenchymal stromal cells (hMSCs) 167:218 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 4 20 theme live 792:795 arg1 mice 797:800 live mice 792:800 live mice with luciferase-transfected hMSCs transplanted into their brains 792:865 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 1 21 theme human 180:184 arg1 hMSCs 213:217 hMSCs 213:217 hMSCs 213:217 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 1 21 theme human 180:184 arg1 cells 206:210 transplanted human mesenchymal stromal cells 167:210 transplanted human mesenchymal stromal cells (hMSCs) 167:218 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 3 22 theme transplanted 670:681 arg1 hMSCs 683:687 transplanted hMSCs 670:687 transplanted hMSCs 670:687 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 4 23 theme luciferase-transfected 807:828 arg1 hMSCs 830:834 luciferase-transfected hMSCs 807:834 luciferase-transfected hMSCs transplanted into their brains 807:865 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 2 24 theme reporter 302:309 arg1 genes 311:315 reporter genes 302:315 reporter genes 302:315 However, reporter genes and exogenous labels may require bespoke manufacturing and regulatory processes if used in cell therapies, and the labels may alter the cells' properties and are diluted on cellular division. 35132228 4 25 with staining 893:900 arg1 lectin 926:931 a mannose-specific lectin 907:931 a mannose-specific lectin 907:931 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 1 26 theme mesenchymal 186:196 arg1 hMSCs 213:217 hMSCs 213:217 hMSCs 213:217 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 1 26 theme mesenchymal 186:196 arg1 cells 206:210 transplanted human mesenchymal stromal cells 167:210 transplanted human mesenchymal stromal cells (hMSCs) 167:218 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 0 27 theme In 0:1 arg1 tracking 8:15 In vivo tracking 0:15 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 0:118 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 3 28 theme exchange 718:725 arg1 resonance 763:771 chemical exchange saturation transfer (CEST) magnetic resonance 709:771 mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 692:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 1 29 theme stromal 198:204 arg1 hMSCs 213:217 hMSCs 213:217 hMSCs 213:217 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 1 29 theme stromal 198:204 arg1 cells 206:210 transplanted human mesenchymal stromal cells 167:210 transplanted human mesenchymal stromal cells (hMSCs) 167:218 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 4 30 theme bioluminescence 1010:1024 arg1 intensity 1026:1034 the bioluminescence intensity 1006:1034 the bioluminescence intensity of viable hMSCs for 14 days 1006:1062 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 1 31 theme exogenous 267:275 arg1 agents 285:290 exogenous imaging agents 267:290 exogenous imaging agents 267:290 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 1 32 dep in 140:141 arg1 vivo 143:146 vivo 143:146 vivo 143:146 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 4 33 theme MRI 967:969 arg1 signal 971:976 the CEST MRI signal 958:976 the CEST MRI signal 958:976 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 1 34 theme cells 206:210 arg1 biodistribution 148:162 the in vivo biodistribution 136:162 the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) 136:218 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 6 35 dep development 1302:1312 arg1 the 1298:1300 the 1298:1300 the 1298:1300 The label-free imaging of hMSCs may facilitate the development and testing of cell therapies. 35132228 1 36 theme imaging 277:283 arg1 agents 285:290 exogenous imaging agents 267:290 exogenous imaging agents 267:290 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 2 37 theme manufacturing 358:370 arg1 processes 387:395 bespoke manufacturing and regulatory processes 350:395 bespoke manufacturing and regulatory processes 350:395 However, reporter genes and exogenous labels may require bespoke manufacturing and regulatory processes if used in cell therapies, and the labels may alter the cells' properties and are diluted on cellular division. 35132228 3 38 theme high-mannose 527:538 arg1 biomarker 629:637 a biomarker 627:637 a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 627:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 3 38 theme high-mannose 527:538 arg1 glycans 549:555 high-mannose N-linked glycans 527:555 high-mannose N-linked glycans 527:555 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 2 39 theme cell 408:411 arg1 therapies 413:421 cell therapies 408:421 cell therapies 408:421 However, reporter genes and exogenous labels may require bespoke manufacturing and regulatory processes if used in cell therapies, and the labels may alter the cells' properties and are diluted on cellular division. 35132228 0 40 theme mesenchymal 31:41 arg1 cells 51:55 unlabelled mesenchymal stromal cells 20:55 unlabelled mesenchymal stromal cells 20:55 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 1 41 theme agents 285:290 arg1 addition 255:262 the addition 251:262 the addition of exogenous imaging agents 251:290 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 4 42 theme mannose-specific 909:924 arg1 lectin 926:931 a mannose-specific lectin 907:931 a mannose-specific lectin 907:931 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 4 43 with mice 797:800 arg1 hMSCs 830:834 luciferase-transfected hMSCs 807:834 luciferase-transfected hMSCs transplanted into their brains 807:865 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 0 44 theme unlabelled 20:29 arg1 cells 51:55 unlabelled mesenchymal stromal cells 20:55 unlabelled mesenchymal stromal cells 20:55 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 3 45 theme CEST 748:751 arg1 resonance 763:771 chemical exchange saturation transfer (CEST) magnetic resonance 709:771 mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 692:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 3 46 theme magnetic 754:761 arg1 resonance 763:771 chemical exchange saturation transfer (CEST) magnetic resonance 709:771 mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 692:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 5 47 theme lower 1159:1163 arg1 intensities 1181:1191 lower CEST MRI signal intensities 1159:1191 lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose 1159:1248 In vitro, osteogenically differentiated hMSCs led to lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose. 35132228 3 48 theme resonance 763:771 arg1 imaging 773:779 mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging 692:779 mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 692:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 3 48 theme resonance 763:771 arg1 MRI 782:784 MRI 782:784 MRI 782:784 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 0 49 theme cells 51:55 arg1 tracking 8:15 In vivo tracking 0:15 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 0:118 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 3 50 theme saturation 727:736 arg1 resonance 763:771 chemical exchange saturation transfer (CEST) magnetic resonance 709:771 mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 692:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 6 51 theme hMSCs 1277:1281 arg1 imaging 1266:1272 The label-free imaging 1251:1272 The label-free imaging of hMSCs 1251:1281 The label-free imaging of hMSCs may facilitate the development and testing of cell therapies. 35132228 0 52 theme stromal 43:49 arg1 cells 51:55 unlabelled mesenchymal stromal cells 20:55 unlabelled mesenchymal stromal cells 20:55 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 3 53 theme transfer 738:745 arg1 resonance 763:771 chemical exchange saturation transfer (CEST) magnetic resonance 709:771 mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 692:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 2 54 theme exogenous 321:329 arg1 labels 331:336 exogenous labels 321:336 exogenous labels 321:336 However, reporter genes and exogenous labels may require bespoke manufacturing and regulatory processes if used in cell therapies, and the labels may alter the cells' properties and are diluted on cellular division. 35132228 3 55 theme N-linked 540:547 arg1 biomarker 629:637 a biomarker 627:637 a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 627:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 3 55 theme N-linked 540:547 arg1 glycans 549:555 high-mannose N-linked glycans 527:555 high-mannose N-linked glycans 527:555 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 4 56 theme fluorescence 880:891 arg1 staining 893:900 post-mortem fluorescence staining 868:900 post-mortem fluorescence staining with a mannose-specific lectin 868:931 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 3 57 theme mannose-weighted 692:707 arg1 imaging 773:779 mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging 692:779 mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 692:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 3 57 theme mannose-weighted 692:707 arg1 MRI 782:784 MRI 782:784 MRI 782:784 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 4 58 theme post-mortem 868:878 arg1 staining 893:900 post-mortem fluorescence staining 868:900 post-mortem fluorescence staining with a mannose-specific lectin 868:931 For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. 35132228 5 59 theme CEST 1165:1168 arg1 intensities 1181:1191 lower CEST MRI signal intensities 1159:1191 lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose 1159:1248 In vitro, osteogenically differentiated hMSCs led to lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose. 35132228 6 60 theme therapies 1334:1342 arg1 development 1302:1312 development 1302:1312 development 1302:1312 The label-free imaging of hMSCs may facilitate the development and testing of cell therapies. 35132228 6 60 theme therapies 1334:1342 arg1 testing 1318:1324 testing 1318:1324 testing 1318:1324 The label-free imaging of hMSCs may facilitate the development and testing of cell therapies. 35132228 0 61 theme mannose-weighted 60:75 arg1 MRI 115:117 mannose-weighted chemical exchange saturation transfer MRI 60:117 mannose-weighted chemical exchange saturation transfer MRI 60:117 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 5 62 theme mannose 1242:1248 arg1 expression 1228:1237 the concomitantly reduced expression 1202:1237 the concomitantly reduced expression of mannose 1202:1248 In vitro, osteogenically differentiated hMSCs led to lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose. 35132228 1 63 theme in 140:141 arg1 biodistribution 148:162 the in vivo biodistribution 136:162 the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) 136:218 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 1 64 theme reporter 230:237 arg1 genes 239:243 reporter genes 230:243 reporter genes 230:243 The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. 35132228 5 65 theme signal 1174:1179 arg1 intensities 1181:1191 lower CEST MRI signal intensities 1159:1191 lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose 1159:1248 In vitro, osteogenically differentiated hMSCs led to lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose. 35132228 3 66 theme label-free 647:656 arg1 tracking 658:665 the label-free tracking 643:665 the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) 643:785 Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). 35132228 0 67 dep In 0:1 arg1 vivo 3:6 vivo 3:6 vivo 3:6 In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI. 35132228 2 68 theme bespoke 350:356 arg1 processes 387:395 bespoke manufacturing and regulatory processes 350:395 bespoke manufacturing and regulatory processes 350:395 However, reporter genes and exogenous labels may require bespoke manufacturing and regulatory processes if used in cell therapies, and the labels may alter the cells' properties and are diluted on cellular division. 35132228 5 69 theme reduced 1220:1226 arg1 expression 1228:1237 the concomitantly reduced expression 1202:1237 the concomitantly reduced expression of mannose 1202:1248 In vitro, osteogenically differentiated hMSCs led to lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose. 35132228 2 70 theme cellular 490:497 arg1 division 499:506 cellular division 490:506 cellular division 490:506 However, reporter genes and exogenous labels may require bespoke manufacturing and regulatory processes if used in cell therapies, and the labels may alter the cells' properties and are diluted on cellular division. 33529335 0 0 theme domain 70:75 arg1 inhibitor 97:105 an anti-C1 domain pathogenic antibody inhibitor 59:105 an anti-C1 domain pathogenic antibody inhibitor 59:105 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 6 1 theme 2A9 869:871 arg1 epitope 873:879 the 2A9 epitope 865:879 the 2A9 epitope 865:879 Most of the C1 domain loops in the 2A9 epitope also represent a putative interface between fVIII and von Willebrand factor. 33529335 8 2 theme inhibitor 1207:1215 arg1 complex 1217:1223 the first fVIII:inhibitor complex 1191:1223 the first fVIII:inhibitor complex with a therapeutically active fVIII construct 1191:1269 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 4 3 theme 2A9 543:545 arg1 epitope 547:553 The 2A9 epitope 539:553 The 2A9 epitope 539:553 The 2A9 epitope forms direct contacts to the C1 domain at 3 different surface loops consisting of Lys2065-Trp2070, Arg2150-Tyr2156, and Lys2110-Trp2112. 33529335 0 4 theme anti-C1 62:68 arg1 inhibitor 97:105 an anti-C1 domain pathogenic antibody inhibitor 59:105 an anti-C1 domain pathogenic antibody inhibitor 59:105 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 3 5 from structure 404:412 arg1 complex 468:474 complex 468:474 complex with a B domain-deleted, bioengineered fVIII construct (ET3i) 468:536 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 9 6 theme replacement 1392:1402 arg1 therapies 1404:1412 more effective and safe fVIII replacement therapies 1362:1412 more effective and safe fVIII replacement therapies 1362:1412 Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies. 33529335 2 7 theme inhibitor 355:363 arg1 response 365:372 a pathogenic inhibitor response 342:372 a pathogenic inhibitor response 342:372 Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. 33529335 2 8 from domain 321:326 arg1 present 303:309 present 303:309 present 303:309 Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. 33529335 8 9 theme anti-C1 1153:1159 arg1 inhibitor 1177:1185 an anti-C1 domain antibody inhibitor 1150:1185 an anti-C1 domain antibody inhibitor 1150:1185 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 0 10 theme antibody 88:95 arg1 inhibitor 97:105 an anti-C1 domain pathogenic antibody inhibitor 59:105 an anti-C1 domain pathogenic antibody inhibitor 59:105 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 0 11 from Structure 0:8 arg1 complex 46:52 complex 46:52 complex with an anti-C1 domain pathogenic antibody inhibitor 46:105 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 9 12 theme safe 1381:1384 arg1 therapies 1404:1412 more effective and safe fVIII replacement therapies 1362:1412 more effective and safe fVIII replacement therapies 1362:1412 Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies. 33529335 2 13 theme present 303:309 arg1 epitopes 294:301 epitopes 294:301 epitopes present in the C1 domain 294:326 Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. 33529335 4 14 theme surface 609:615 arg1 loops 617:621 3 different surface loops 597:621 3 different surface loops consisting of Lys2065-Trp2070, Arg2150-Tyr2156, and Lys2110-Trp2112 597:689 The 2A9 epitope forms direct contacts to the C1 domain at 3 different surface loops consisting of Lys2065-Trp2070, Arg2150-Tyr2156, and Lys2110-Trp2112. 33529335 6 15 theme Willebrand 939:948 arg1 factor 950:955 von Willebrand factor 935:955 von Willebrand factor 935:955 Most of the C1 domain loops in the 2A9 epitope also represent a putative interface between fVIII and von Willebrand factor. 33529335 0 16 theme pathogenic 77:86 arg1 inhibitor 97:105 an anti-C1 domain pathogenic antibody inhibitor 59:105 an anti-C1 domain pathogenic antibody inhibitor 59:105 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 0 17 from complex 46:52 arg1 Structure 0:8 Structure 0:8 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 0:106 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 5 18 link N-linked 799:806 arg1 glycosylation 808:820 the N-linked glycosylation 795:820 the N-linked glycosylation at Asn1810 795:831 Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. 33529335 8 19 theme fVIII 1255:1259 arg1 construct 1261:1269 a therapeutically active fVIII construct 1230:1269 a therapeutically active fVIII construct 1230:1269 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 6 20 theme von 935:937 arg1 factor 950:955 von Willebrand factor 935:955 von Willebrand factor 935:955 Most of the C1 domain loops in the 2A9 epitope also represent a putative interface between fVIII and von Willebrand factor. 33529335 6 21 from loops 856:860 arg1 epitope 873:879 the 2A9 epitope 865:879 the 2A9 epitope 865:879 Most of the C1 domain loops in the 2A9 epitope also represent a putative interface between fVIII and von Willebrand factor. 33529335 2 22 theme pathogenic 344:353 arg1 response 365:372 a pathogenic inhibitor response 342:372 a pathogenic inhibitor response 342:372 Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. 33529335 5 23 theme N-linked 799:806 arg1 glycosylation 808:820 the N-linked glycosylation 795:820 the N-linked glycosylation at Asn1810 795:831 Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. 33529335 4 24 theme C1 584:585 arg1 domain 587:592 the C1 domain 580:592 the C1 domain 580:592 The 2A9 epitope forms direct contacts to the C1 domain at 3 different surface loops consisting of Lys2065-Trp2070, Arg2150-Tyr2156, and Lys2110-Trp2112. 33529335 9 25 theme fVIII 1386:1390 arg1 therapies 1404:1412 more effective and safe fVIII replacement therapies 1362:1412 more effective and safe fVIII replacement therapies 1362:1412 Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies. 33529335 3 26 theme A 425:425 arg1 inhibitor 442:450 a group A anti-C1 domain inhibitor 417:450 a group A anti-C1 domain inhibitor 417:450 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 9 27 theme effective 1367:1375 arg1 therapies 1404:1412 more effective and safe fVIII replacement therapies 1362:1412 more effective and safe fVIII replacement therapies 1362:1412 Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies. 33529335 0 28 from VIII 38:41 arg1 complex 46:52 complex 46:52 complex with an anti-C1 domain pathogenic antibody inhibitor 46:105 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 5 29 theme A3 745:746 arg1 domain 748:753 the A3 domain 741:753 the A3 domain 741:753 Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. 33529335 1 30 from development 127:137 arg1 A 153:153 hemophilia A 142:153 hemophilia A 142:153 Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. 33529335 1 31 theme significant 175:185 arg1 complication 187:198 the most significant complication 166:198 the most significant complication resulting from factor VIII (fVIII) replacement therapy 166:253 Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. 33529335 7 32 dep large 1013:1017 arg1 novel 1020:1024 novel 1020:1024 novel 1020:1024 Lastly, the C2 domain in the ET3i:2A9 complex adopts a large, novel conformational change, translocating outward from the structure of fVIII by 20 Å. 33529335 4 33 theme different 599:607 arg1 loops 617:621 3 different surface loops 597:621 3 different surface loops consisting of Lys2065-Trp2070, Arg2150-Tyr2156, and Lys2110-Trp2112 597:689 The 2A9 epitope forms direct contacts to the C1 domain at 3 different surface loops consisting of Lys2065-Trp2070, Arg2150-Tyr2156, and Lys2110-Trp2112. 33529335 6 34 theme domain 849:854 arg1 loops 856:860 the C1 domain loops 842:860 the C1 domain loops in the 2A9 epitope 842:879 Most of the C1 domain loops in the 2A9 epitope also represent a putative interface between fVIII and von Willebrand factor. 33529335 8 35 theme inhibitor 1177:1185 arg1 complex 1217:1223 the first fVIII:inhibitor complex 1191:1223 the first fVIII:inhibitor complex with a therapeutically active fVIII construct 1191:1269 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 8 35 theme inhibitor 1177:1185 arg1 structure 1137:1145 the first structure 1127:1145 the first structure of an anti-C1 domain antibody inhibitor 1127:1185 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 5 36 theme Phe1743-Tyr1748 770:784 arg1 loop 786:789 the Phe1743-Tyr1748 loop 766:789 the Phe1743-Tyr1748 loop 766:789 Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. 33529335 3 37 with complex 468:474 arg1 ET3i 532:535 ET3i 532:535 ET3i 532:535 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 3 37 with complex 468:474 arg1 construct 521:529 a B domain-deleted, bioengineered fVIII construct 481:529 a B domain-deleted, bioengineered fVIII construct (ET3i) 481:536 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 2 38 theme C1 318:319 arg1 domain 321:326 the C1 domain 314:326 the C1 domain 314:326 Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. 33529335 5 39 theme Additional 692:701 arg1 contacts 703:710 Additional contacts 692:710 Additional contacts 692:710 Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. 33529335 3 40 theme group 419:423 arg1 inhibitor 442:450 a group A anti-C1 domain inhibitor 417:450 a group A anti-C1 domain inhibitor 417:450 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 0 41 theme coagulation 19:29 arg1 VIII 38:41 blood coagulation factor VIII 13:41 blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor 13:105 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 8 42 theme domain 1161:1166 arg1 inhibitor 1177:1185 an anti-C1 domain antibody inhibitor 1150:1185 an anti-C1 domain antibody inhibitor 1150:1185 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 8 43 theme active 1248:1253 arg1 construct 1261:1269 a therapeutically active fVIII construct 1230:1269 a therapeutically active fVIII construct 1230:1269 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 9 44 theme immunogenicity 1314:1327 arg1 understanding 1291:1303 Further structural understanding 1272:1303 Further structural understanding of fVIII immunogenicity 1272:1327 Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies. 33529335 7 45 theme C2 970:971 arg1 domain 973:978 the C2 domain 966:978 the C2 domain in the ET3i:2A9 complex 966:1002 Lastly, the C2 domain in the ET3i:2A9 complex adopts a large, novel conformational change, translocating outward from the structure of fVIII by 20 Å. 33529335 0 46 theme blood 13:17 arg1 VIII 38:41 blood coagulation factor VIII 13:41 blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor 13:105 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 9 47 theme Further 1272:1278 arg1 understanding 1291:1303 Further structural understanding 1272:1303 Further structural understanding of fVIII immunogenicity 1272:1327 Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies. 33529335 7 48 theme large 1013:1017 arg1 change 1041:1046 a large, novel conformational change 1011:1046 a large, novel conformational change 1011:1046 Lastly, the C2 domain in the ET3i:2A9 complex adopts a large, novel conformational change, translocating outward from the structure of fVIII by 20 Å. 33529335 3 49 dep domain-deleted 485:498 arg1 bioengineered 501:513 bioengineered 501:513 bioengineered 501:513 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 1 50 theme factor 215:220 arg1 fVIII 228:232 fVIII 228:232 fVIII 228:232 Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. 33529335 1 50 theme factor 215:220 arg1 VIII 222:225 factor VIII 215:225 factor VIII (fVIII) replacement therapy 215:253 Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. 33529335 0 51 theme VIII 38:41 arg1 Structure 0:8 Structure 0:8 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 0:106 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 9 52 theme structural 1280:1289 arg1 understanding 1291:1303 Further structural understanding 1272:1303 Further structural understanding of fVIII immunogenicity 1272:1327 Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies. 33529335 3 53 theme domain 435:440 arg1 inhibitor 442:450 a group A anti-C1 domain inhibitor 417:450 a group A anti-C1 domain inhibitor 417:450 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 8 54 theme antibody 1168:1175 arg1 inhibitor 1177:1185 an anti-C1 domain antibody inhibitor 1150:1185 an anti-C1 domain antibody inhibitor 1150:1185 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 1 55 theme VIII 222:225 arg1 therapy 247:253 factor VIII (fVIII) replacement therapy 215:253 factor VIII (fVIII) replacement therapy 215:253 Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. 33529335 0 56 theme factor 31:36 arg1 VIII 38:41 blood coagulation factor VIII 13:41 blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor 13:105 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 6 57 theme putative 898:905 arg1 interface 907:915 a putative interface 896:915 a putative interface between fVIII and von Willebrand factor 896:955 Most of the C1 domain loops in the 2A9 epitope also represent a putative interface between fVIII and von Willebrand factor. 33529335 7 58 theme fVIII 1093:1097 arg1 structure 1080:1088 the structure 1076:1088 the structure of fVIII by 20 Å 1076:1105 Lastly, the C2 domain in the ET3i:2A9 complex adopts a large, novel conformational change, translocating outward from the structure of fVIII by 20 Å. 33529335 8 59 theme fVIII 1201:1205 arg1 complex 1217:1223 the first fVIII:inhibitor complex 1191:1223 the first fVIII:inhibitor complex with a therapeutically active fVIII construct 1191:1269 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 3 60 theme inhibitor 442:450 arg1 structure 404:412 the structure 400:412 the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i) 400:536 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 8 61 with complex 1217:1223 arg1 construct 1261:1269 a therapeutically active fVIII construct 1230:1269 a therapeutically active fVIII construct 1230:1269 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 2 62 attach present 303:309 arg1 domain 321:326 the C1 domain 314:326 the C1 domain 314:326 Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. 33529335 2 62 attach present 303:309 arg2 epitopes 294:301 epitopes 294:301 epitopes present in the C1 domain 294:326 Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. 33529335 8 63 theme first 1131:1135 arg1 structure 1137:1145 the first structure 1127:1145 the first structure of an anti-C1 domain antibody inhibitor 1127:1185 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 6 64 theme C1 846:847 arg1 loops 856:860 the C1 domain loops 842:860 the C1 domain loops in the 2A9 epitope 842:879 Most of the C1 domain loops in the 2A9 epitope also represent a putative interface between fVIII and von Willebrand factor. 33529335 1 65 theme Antibody 108:115 arg1 development 127:137 Antibody inhibitor development 108:137 Antibody inhibitor development in hemophilia A 108:153 Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. 33529335 9 66 theme fVIII 1308:1312 arg1 immunogenicity 1314:1327 fVIII immunogenicity 1308:1327 fVIII immunogenicity 1308:1327 Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies. 33529335 7 67 theme ET3i:2A9 987:994 arg1 complex 996:1002 the ET3i:2A9 complex 983:1002 the ET3i:2A9 complex 983:1002 Lastly, the C2 domain in the ET3i:2A9 complex adopts a large, novel conformational change, translocating outward from the structure of fVIII by 20 Å. 33529335 1 68 theme inhibitor 117:125 arg1 development 127:137 Antibody inhibitor development 108:137 Antibody inhibitor development in hemophilia A 108:153 Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. 33529335 8 69 with structure 1137:1145 arg1 construct 1261:1269 a therapeutically active fVIII construct 1230:1269 a therapeutically active fVIII construct 1230:1269 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 7 70 theme conformational 1026:1039 arg1 change 1041:1046 a large, novel conformational change 1011:1046 a large, novel conformational change 1011:1046 Lastly, the C2 domain in the ET3i:2A9 complex adopts a large, novel conformational change, translocating outward from the structure of fVIII by 20 Å. 33529335 5 71 gly glycosylation 808:820 arg2 Asn1810 825:831 Asn1810 825:831 Asn1810 825:831 Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. 33529335 5 71 gly glycosylation 808:820 arg1 Asn1810 825:831 Asn1810 825:831 Asn1810 825:831 Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. 33529335 7 72 from domain 973:978 arg1 complex 996:1002 the ET3i:2A9 complex 983:1002 the ET3i:2A9 complex 983:1002 Lastly, the C2 domain in the ET3i:2A9 complex adopts a large, novel conformational change, translocating outward from the structure of fVIII by 20 Å. 33529335 3 73 theme fVIII 515:519 arg1 ET3i 532:535 ET3i 532:535 ET3i 532:535 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 3 73 theme fVIII 515:519 arg1 construct 521:529 a B domain-deleted, bioengineered fVIII construct 481:529 a B domain-deleted, bioengineered fVIII construct (ET3i) 481:536 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 0 74 with complex 46:52 arg1 inhibitor 97:105 an anti-C1 domain pathogenic antibody inhibitor 59:105 an anti-C1 domain pathogenic antibody inhibitor 59:105 Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. 33529335 2 75 from present 303:309 arg1 domain 321:326 the C1 domain 314:326 the C1 domain 314:326 Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. 33529335 4 76 theme direct 561:566 arg1 contacts 568:575 direct contacts 561:575 direct contacts to the C1 domain 561:592 The 2A9 epitope forms direct contacts to the C1 domain at 3 different surface loops consisting of Lys2065-Trp2070, Arg2150-Tyr2156, and Lys2110-Trp2112. 33529335 8 77 theme first 1195:1199 arg1 complex 1217:1223 the first fVIII:inhibitor complex 1191:1223 the first fVIII:inhibitor complex with a therapeutically active fVIII construct 1191:1269 This study reports the first structure of an anti-C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. 33529335 2 78 theme Recent 256:261 arg1 studies 263:269 Recent studies 256:269 Recent studies 256:269 Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. 33529335 9 79 theme therapies 1404:1412 arg1 development 1347:1357 the development 1343:1357 the development of more effective and safe fVIII replacement therapies 1343:1412 Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies. 33529335 1 80 theme hemophilia 142:151 arg1 A 153:153 hemophilia A 142:153 hemophilia A 142:153 Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. 33529335 3 81 theme anti-C1 427:433 arg1 inhibitor 442:450 a group A anti-C1 domain inhibitor 417:450 a group A anti-C1 domain inhibitor 417:450 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 1 82 theme replacement 235:245 arg1 therapy 247:253 factor VIII (fVIII) replacement therapy 215:253 factor VIII (fVIII) replacement therapy 215:253 Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. 33529335 5 83 from Asn1810 825:831 arg1 glycosylation 808:820 the N-linked glycosylation 795:820 the N-linked glycosylation at Asn1810 795:831 Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. 33529335 5 83 from Asn1810 825:831 arg1 loop 786:789 the Phe1743-Tyr1748 loop 766:789 the Phe1743-Tyr1748 loop 766:789 Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. 33529335 3 84 theme domain-deleted 485:498 arg1 ET3i 532:535 ET3i 532:535 ET3i 532:535 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33529335 3 84 theme domain-deleted 485:498 arg1 construct 521:529 a B domain-deleted, bioengineered fVIII construct 481:529 a B domain-deleted, bioengineered fVIII construct (ET3i) 481:536 In this study, we report the structure of a group A anti-C1 domain inhibitor, termed 2A9, in complex with a B domain-deleted, bioengineered fVIII construct (ET3i). 33522411 8 0 theme COOH-terminal 1049:1061 arg1 fragments 1063:1071 COOH-terminal fragments 1049:1071 COOH-terminal fragments 1049:1071 This was confirmed using nonreducing gels, in which the NH2- and COOH-terminal fragments of γENaC are linked by a disulfide bond. 33522411 6 1 theme surface 836:842 arg1 fractions 844:852 cell surface fractions 831:852 cell surface fractions 831:852 Similar cleaved peptides were observed in total and cell surface fractions of the rat kidney. 33522411 2 2 from diet 252:255 arg1 state 185:189 the cleavage state 172:189 the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet 172:255 Here, we investigated the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet. 33522411 4 3 theme mouse 520:524 arg1 kidney 526:531 the mouse kidney 516:531 the mouse kidney 516:531 To compare the peptides produced in the heterologous system with those in the mouse kidney, we treated both lysates with PNGaseF to remove N-linked glycosylation. 33522411 10 4 theme mouse 1423:1427 arg1 kidneys 1429:1435 rat and mouse kidneys 1415:1435 rat and mouse kidneys 1415:1435 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 5 dep twice-cleaved 1461:1473 arg1 activated 1487:1495 activated 1487:1495 activated 1487:1495 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 2 6 theme mice 224:227 arg1 kidneys 213:219 the kidneys 209:219 the kidneys of mice and rats on a low-salt diet 209:255 Here, we investigated the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet. 33522411 11 7 theme protease 1766:1773 arg1 protease 1794:1801 the extracellular protease channel-activating protease 1 1748:1803 the extracellular protease channel-activating protease 1 (prostasin) 1748:1815 This form appears to be identical in size with a subunit cleaved in vitro by the extracellular protease channel-activating protease 1 (prostasin). 33522411 11 7 theme protease 1766:1773 arg1 prostasin 1806:1814 prostasin 1806:1814 prostasin 1806:1814 This form appears to be identical in size with a subunit cleaved in vitro by the extracellular protease channel-activating protease 1 (prostasin). 33522411 12 8 theme consistent 1924:1933 arg1 subunit 1915:1921 the intact subunit 1904:1921 the intact subunit 1904:1921 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 10 9 theme rat 1415:1417 arg1 kidneys 1429:1435 rat and mouse kidneys 1415:1435 rat and mouse kidneys 1415:1435 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 5 10 theme CAP1-induced 729:740 arg1 species 742:748 the CAP1-induced species 725:748 the CAP1-induced species in Fisher rat thyroid cells 725:776 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 9 11 theme peptide 1305:1311 arg1 excision 1285:1292 excision 1285:1292 excision of a short peptide by two proteolytic events 1285:1337 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 10 12 from form 1578:1581 arg1 kidney 1636:1641 the kidney 1632:1641 the kidney 1632:1641 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 13 theme low-Na 1442:1447 arg1 diet 1449:1452 a low-Na diet 1440:1452 a low-Na diet 1440:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 14 theme subunit 1621:1627 arg1 peptide 1662:1668 a twice-cleaved peptide 1646:1668 a twice-cleaved peptide 1646:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 14 theme subunit 1621:1627 arg1 form 1578:1581 the major aldosterone-dependent cleaved form 1538:1581 the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney 1538:1641 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 8 15 theme disulfide 1098:1106 arg1 bond 1108:1111 a disulfide bond 1096:1111 a disulfide bond 1096:1111 This was confirmed using nonreducing gels, in which the NH2- and COOH-terminal fragments of γENaC are linked by a disulfide bond. 33522411 2 16 theme rats 233:236 arg1 kidneys 213:219 the kidneys 209:219 the kidneys of mice and rats on a low-salt diet 209:255 Here, we investigated the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet. 33522411 5 17 theme rat 760:762 arg1 cells 772:776 Fisher rat thyroid cells 753:776 Fisher rat thyroid cells 753:776 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 12 18 contain has 1856:1858 arg2 mass 1881:1884 an overall molecular mass 1860:1884 an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain 1860:1975 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 12 18 contain has 1856:1858 arg1 it 1853:1854 it 1853:1854 it 1853:1854 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 8 19 attach linked 1086:1091 arg3 bond 1108:1111 a disulfide bond 1096:1111 a disulfide bond 1096:1111 This was confirmed using nonreducing gels, in which the NH2- and COOH-terminal fragments of γENaC are linked by a disulfide bond. 33522411 8 19 attach linked 1086:1091 arg3 gels 1021:1024 nonreducing gels 1009:1024 nonreducing gels 1009:1024 This was confirmed using nonreducing gels, in which the NH2- and COOH-terminal fragments of γENaC are linked by a disulfide bond. 33522411 8 19 attach linked 1086:1091 arg2 fragments 1063:1071 COOH-terminal fragments 1049:1071 COOH-terminal fragments 1049:1071 This was confirmed using nonreducing gels, in which the NH2- and COOH-terminal fragments of γENaC are linked by a disulfide bond. 33522411 8 19 attach linked 1086:1091 arg2 NH2- 1040:1043 NH2- 1040:1043 NH2- 1040:1043 This was confirmed using nonreducing gels, in which the NH2- and COOH-terminal fragments of γENaC are linked by a disulfide bond. 33522411 10 20 theme twice-cleaved 1461:1473 arg1 species 1381:1387 the most abundant γENaC species 1357:1387 the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet 1357:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 20 theme twice-cleaved 1461:1473 arg1 NOTEWORTHY 1508:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY 1457:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide 1457:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 5 21 theme smallest 640:647 arg1 fragment 663:670 the smallest COOH-terminal fragment 636:670 the smallest COOH-terminal fragment of γENaC (52 kDa) 636:688 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 6 22 theme rat 861:863 arg1 kidney 865:870 the rat kidney 857:870 the rat kidney 857:870 Similar cleaved peptides were observed in total and cell surface fractions of the rat kidney. 33522411 12 23 theme less 1886:1889 arg1 mass 1881:1884 an overall molecular mass 1860:1884 an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain 1860:1975 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 9 24 theme cleaved 1148:1154 arg1 form 1156:1159 the major cleaved form 1138:1159 the major cleaved form in the rat kidney 1138:1177 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 11 25 theme channel-activating 1775:1792 arg1 protease 1794:1801 the extracellular protease channel-activating protease 1 1748:1803 the extracellular protease channel-activating protease 1 (prostasin) 1748:1815 This form appears to be identical in size with a subunit cleaved in vitro by the extracellular protease channel-activating protease 1 (prostasin). 33522411 11 25 theme channel-activating 1775:1792 arg1 prostasin 1806:1814 prostasin 1806:1814 prostasin 1806:1814 This form appears to be identical in size with a subunit cleaved in vitro by the extracellular protease channel-activating protease 1 (prostasin). 33522411 5 26 theme molecular 618:626 arg1 indistinguishable 694:710 indistinguishable 694:710 indistinguishable 694:710 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 5 26 theme molecular 618:626 arg1 mass 628:631 The apparent molecular mass 605:631 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) 605:688 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 10 27 from diet 1449:1452 arg1 species 1381:1387 the most abundant γENaC species 1357:1387 the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet 1357:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 27 from diet 1449:1452 arg1 NOTEWORTHY 1508:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY 1457:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide 1457:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 9 28 theme rat 1168:1170 arg1 kidney 1172:1177 the rat kidney 1164:1177 the rat kidney 1164:1177 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 10 29 theme twice-cleaved 1648:1660 arg1 peptide 1662:1668 a twice-cleaved peptide 1646:1668 a twice-cleaved peptide 1646:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 29 theme twice-cleaved 1648:1660 arg1 form 1578:1581 the major aldosterone-dependent cleaved form 1538:1581 the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney 1538:1641 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 12 30 theme molecular 1871:1879 arg1 mass 1881:1884 an overall molecular mass 1860:1884 an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain 1860:1975 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 5 31 theme fragment 663:670 arg1 indistinguishable 694:710 indistinguishable 694:710 indistinguishable 694:710 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 5 31 theme fragment 663:670 arg1 mass 628:631 The apparent molecular mass 605:631 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) 605:688 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 5 32 from species 742:748 arg1 cells 772:776 Fisher rat thyroid cells 753:776 Fisher rat thyroid cells 753:776 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 3 33 dep CAP1 424:427 arg1 prostasin 430:438 prostasin 430:438 CAP1; prostasin 424:438 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 10 34 from species 1381:1387 arg1 membrane 1403:1410 the apical membrane 1392:1410 the apical membrane of rat and mouse kidneys on a low-Na diet 1392:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 34 from species 1381:1387 arg1 diet 1449:1452 a low-Na diet 1440:1452 a low-Na diet 1440:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 9 35 contain had 1179:1181 arg1 form 1156:1159 the major cleaved form 1138:1159 the major cleaved form in the rat kidney 1138:1177 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 9 35 contain had 1179:1181 arg2 mass 1205:1208 an apparent molecular mass 1183:1208 an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form 1183:1266 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 3 36 theme apical 362:367 arg1 protease 412:419 the apical membrane-bound protease channel-activating protease 1 358:421 the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin) 358:439 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 3 36 theme apical 362:367 arg1 CAP1 424:427 CAP1 424:427 CAP1; prostasin 424:438 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 5 37 theme γENaC 675:679 arg1 fragment 663:670 the smallest COOH-terminal fragment 636:670 the smallest COOH-terminal fragment of γENaC (52 kDa) 636:688 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 8 38 dep NH2- 1040:1043 arg1 the 1036:1038 the 1036:1038 the 1036:1038 This was confirmed using nonreducing gels, in which the NH2- and COOH-terminal fragments of γENaC are linked by a disulfide bond. 33522411 0 39 theme Cleavage 0:7 arg1 state 9:13 Cleavage state 0:13 Cleavage state of γENaC in mouse and rat kidneys. 0:48 Cleavage state of γENaC in mouse and rat kidneys. 33522411 3 40 theme channels 295:302 arg1 species 284:290 the cleaved species 272:290 the cleaved species of channels expressed in Fisher rat thyroid cells 272:340 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 9 41 theme ∼4 kDa 1221:1226 arg1 mass 1205:1208 an apparent molecular mass 1183:1208 an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form 1183:1266 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 1 42 theme epithelial 91:100 arg1 ENaC 114:117 ENaC 114:117 ENaC 114:117 Extracellular proteases can activate the epithelial Na channel (ENaC) by cleavage of the γ subunit. 33522411 1 42 theme epithelial 91:100 arg1 channel 105:111 the epithelial Na channel 87:111 the epithelial Na channel (ENaC) 87:118 Extracellular proteases can activate the epithelial Na channel (ENaC) by cleavage of the γ subunit. 33522411 3 43 theme protease 384:391 arg1 protease 412:419 the apical membrane-bound protease channel-activating protease 1 358:421 the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin) 358:439 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 3 43 theme protease 384:391 arg1 CAP1 424:427 CAP1 424:427 CAP1; prostasin 424:438 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 6 44 theme Similar 779:785 arg1 peptides 795:802 Similar cleaved peptides 779:802 Similar cleaved peptides 779:802 Similar cleaved peptides were observed in total and cell surface fractions of the rat kidney. 33522411 3 45 theme rat 324:326 arg1 cells 336:340 Fisher rat thyroid cells 317:340 Fisher rat thyroid cells 317:340 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 10 46 theme cleaved 1570:1576 arg1 peptide 1662:1668 a twice-cleaved peptide 1646:1668 a twice-cleaved peptide 1646:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 46 theme cleaved 1570:1576 arg1 form 1578:1581 the major aldosterone-dependent cleaved form 1538:1581 the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney 1538:1641 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 5 47 from that 717:720 arg1 indistinguishable 694:710 indistinguishable 694:710 indistinguishable 694:710 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 5 47 from that 717:720 arg1 mass 628:631 The apparent molecular mass 605:631 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) 605:688 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 10 48 theme γENaC 1375:1379 arg1 species 1381:1387 the most abundant γENaC species 1357:1387 the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet 1357:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 48 theme γENaC 1375:1379 arg1 NOTEWORTHY 1508:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY 1457:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide 1457:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 12 49 theme domain 1970:1975 arg1 excision 1944:1951 the excision 1940:1951 the excision of an inhibitory domain 1940:1975 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 10 50 theme major 1542:1546 arg1 peptide 1662:1668 a twice-cleaved peptide 1646:1668 a twice-cleaved peptide 1646:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 50 theme major 1542:1546 arg1 form 1578:1581 the major aldosterone-dependent cleaved form 1538:1581 the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney 1538:1641 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 9 51 theme full-length 1251:1261 arg1 form 1263:1266 the full-length form 1247:1266 the full-length form 1247:1266 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 10 52 theme Na 1601:1602 arg1 ENaC 1613:1616 ENaC 1613:1616 ENaC 1613:1616 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 52 theme Na 1601:1602 arg1 channel 1604:1610 the epithelial Na channel 1586:1610 the epithelial Na channel (ENaC) γ subunit 1586:1627 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 12 53 theme inhibitory 1959:1968 arg1 domain 1970:1975 an inhibitory domain 1956:1975 an inhibitory domain 1956:1975 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 9 54 with consistent 1269:1278 arg1 excision 1285:1292 excision 1285:1292 excision of a short peptide by two proteolytic events 1285:1337 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 10 55 theme epithelial 1590:1599 arg1 ENaC 1613:1616 ENaC 1613:1616 ENaC 1613:1616 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 55 theme epithelial 1590:1599 arg1 channel 1604:1610 the epithelial Na channel 1586:1610 the epithelial Na channel (ENaC) γ subunit 1586:1627 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 12 56 theme reducing 1836:1843 arg1 agents 1845:1850 reducing agents 1836:1850 reducing agents 1836:1850 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 10 57 theme apical 1396:1401 arg1 membrane 1403:1410 the apical membrane 1392:1410 the apical membrane of rat and mouse kidneys on a low-Na diet 1392:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 11 58 with identical 1695:1703 arg1 subunit 1720:1726 a subunit 1718:1726 a subunit cleaved in vitro by the extracellular protease channel-activating protease 1 (prostasin) 1718:1815 This form appears to be identical in size with a subunit cleaved in vitro by the extracellular protease channel-activating protease 1 (prostasin). 33522411 9 59 from form 1156:1159 arg1 kidney 1172:1177 the rat kidney 1164:1177 the rat kidney 1164:1177 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 6 60 theme cell 831:834 arg1 fractions 844:852 cell surface fractions 831:852 cell surface fractions 831:852 Similar cleaved peptides were observed in total and cell surface fractions of the rat kidney. 33522411 10 61 theme kidneys 1429:1435 arg1 membrane 1403:1410 the apical membrane 1392:1410 the apical membrane of rat and mouse kidneys on a low-Na diet 1392:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 62 theme channel 1604:1610 arg1 subunit 1621:1627 the epithelial Na channel (ENaC) γ subunit 1586:1627 the epithelial Na channel (ENaC) γ subunit 1586:1627 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 9 63 theme short 1299:1303 arg1 peptide 1305:1311 a short peptide 1297:1311 a short peptide 1297:1311 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 8 64 theme γENaC 1076:1080 arg1 NH2- 1040:1043 NH2- 1040:1043 NH2- 1040:1043 This was confirmed using nonreducing gels, in which the NH2- and COOH-terminal fragments of γENaC are linked by a disulfide bond. 33522411 8 64 theme γENaC 1076:1080 arg1 fragments 1063:1071 COOH-terminal fragments 1049:1071 COOH-terminal fragments 1049:1071 This was confirmed using nonreducing gels, in which the NH2- and COOH-terminal fragments of γENaC are linked by a disulfide bond. 33522411 2 65 theme low-salt 243:250 arg1 diet 252:255 a low-salt diet 241:255 a low-salt diet 241:255 Here, we investigated the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet. 33522411 1 66 theme subunit 141:147 arg1 cleavage 123:130 cleavage 123:130 cleavage of the γ subunit 123:147 Extracellular proteases can activate the epithelial Na channel (ENaC) by cleavage of the γ subunit. 33522411 4 67 theme N-linked 581:588 arg1 glycosylation 590:602 N-linked glycosylation 581:602 N-linked glycosylation 581:602 To compare the peptides produced in the heterologous system with those in the mouse kidney, we treated both lysates with PNGaseF to remove N-linked glycosylation. 33522411 10 68 theme γ 1619:1619 arg1 subunit 1621:1627 the epithelial Na channel (ENaC) γ subunit 1586:1627 the epithelial Na channel (ENaC) γ subunit 1586:1627 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 5 69 theme Fisher 753:758 arg1 cells 772:776 Fisher rat thyroid cells 753:776 Fisher rat thyroid cells 753:776 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 7 70 theme extracellular 959:971 arg1 proteases 973:981 extracellular proteases 959:981 extracellular proteases 959:981 This outcome suggests that most of the subunits at the surface have been processed by extracellular proteases. 33522411 6 71 located observed 809:816 arg2 peptides 795:802 Similar cleaved peptides 779:802 Similar cleaved peptides 779:802 Similar cleaved peptides were observed in total and cell surface fractions of the rat kidney. 33522411 6 71 located observed 809:816 arg1 total 821:825 total 821:825 total 821:825 Similar cleaved peptides were observed in total and cell surface fractions of the rat kidney. 33522411 6 71 located observed 809:816 arg1 fractions 844:852 cell surface fractions 831:852 cell surface fractions 831:852 Similar cleaved peptides were observed in total and cell surface fractions of the rat kidney. 33522411 5 72 theme thyroid 764:770 arg1 cells 772:776 Fisher rat thyroid cells 753:776 Fisher rat thyroid cells 753:776 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 6 73 theme kidney 865:870 arg1 total 821:825 total 821:825 total 821:825 Similar cleaved peptides were observed in total and cell surface fractions of the rat kidney. 33522411 6 73 theme kidney 865:870 arg1 fractions 844:852 cell surface fractions 831:852 cell surface fractions 831:852 Similar cleaved peptides were observed in total and cell surface fractions of the rat kidney. 33522411 4 74 link N-linked 581:588 arg1 glycosylation 590:602 N-linked glycosylation 581:602 N-linked glycosylation 581:602 To compare the peptides produced in the heterologous system with those in the mouse kidney, we treated both lysates with PNGaseF to remove N-linked glycosylation. 33522411 7 75 from surface 928:934 arg1 subunits 912:919 the subunits 908:919 the subunits at the surface 908:934 This outcome suggests that most of the subunits at the surface have been processed by extracellular proteases. 33522411 9 76 theme major 1142:1146 arg1 form 1156:1159 the major cleaved form 1138:1159 the major cleaved form in the rat kidney 1138:1177 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 2 77 theme cleavage 176:183 arg1 state 185:189 the cleavage state 172:189 the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet 172:255 Here, we investigated the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet. 33522411 1 78 theme Na 102:103 arg1 ENaC 114:117 ENaC 114:117 ENaC 114:117 Extracellular proteases can activate the epithelial Na channel (ENaC) by cleavage of the γ subunit. 33522411 1 78 theme Na 102:103 arg1 channel 105:111 the epithelial Na channel 87:111 the epithelial Na channel (ENaC) 87:118 Extracellular proteases can activate the epithelial Na channel (ENaC) by cleavage of the γ subunit. 33522411 5 79 theme apparent 609:616 arg1 indistinguishable 694:710 indistinguishable 694:710 indistinguishable 694:710 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 5 79 theme apparent 609:616 arg1 mass 628:631 The apparent molecular mass 605:631 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) 605:688 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 2 80 from kidneys 213:219 arg1 diet 252:255 a low-salt diet 241:255 a low-salt diet 241:255 Here, we investigated the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet. 33522411 2 81 theme channel 198:204 arg1 state 185:189 the cleavage state 172:189 the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet 172:255 Here, we investigated the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet. 33522411 9 82 theme proteolytic 1320:1330 arg1 events 1332:1337 two proteolytic events 1316:1337 two proteolytic events 1316:1337 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 9 83 theme apparent 1186:1193 arg1 mass 1205:1208 an apparent molecular mass 1183:1208 an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form 1183:1266 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 0 84 from state 9:13 arg1 mouse 27:31 mouse 27:31 mouse 27:31 Cleavage state of γENaC in mouse and rat kidneys. 33522411 0 84 from state 9:13 arg1 rat 37:39 rat 37:39 rat 37:39 Cleavage state of γENaC in mouse and rat kidneys. 33522411 11 85 from identical 1695:1703 arg1 size 1708:1711 size 1708:1711 size 1708:1711 This form appears to be identical in size with a subunit cleaved in vitro by the extracellular protease channel-activating protease 1 (prostasin). 33522411 12 86 theme overall 1863:1869 arg1 mass 1881:1884 an overall molecular mass 1860:1884 an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain 1860:1975 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 5 87 theme COOH-terminal 649:661 arg1 fragment 663:670 the smallest COOH-terminal fragment 636:670 the smallest COOH-terminal fragment of γENaC (52 kDa) 636:688 The apparent molecular mass of the smallest COOH-terminal fragment of γENaC (52 kDa) was indistinguishable from that of the CAP1-induced species in Fisher rat thyroid cells. 33522411 11 88 from size 1708:1711 arg1 identical 1695:1703 identical 1695:1703 identical 1695:1703 This form appears to be identical in size with a subunit cleaved in vitro by the extracellular protease channel-activating protease 1 (prostasin). 33522411 9 89 theme molecular 1195:1203 arg1 mass 1205:1208 an apparent molecular mass 1183:1208 an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form 1183:1266 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 1 90 theme Extracellular 50:62 arg1 proteases 64:72 Extracellular proteases 50:72 Extracellular proteases 50:72 Extracellular proteases can activate the epithelial Na channel (ENaC) by cleavage of the γ subunit. 33522411 3 91 theme cleaved 276:282 arg1 species 284:290 the cleaved species 272:290 the cleaved species of channels expressed in Fisher rat thyroid cells 272:340 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 3 92 theme membrane-bound 369:382 arg1 protease 412:419 the apical membrane-bound protease channel-activating protease 1 358:421 the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin) 358:439 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 3 92 theme membrane-bound 369:382 arg1 CAP1 424:427 CAP1 424:427 CAP1; prostasin 424:438 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 2 93 from state 185:189 arg1 diet 252:255 a low-salt diet 241:255 a low-salt diet 241:255 Here, we investigated the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet. 33522411 2 93 from state 185:189 arg1 kidneys 213:219 the kidneys 209:219 the kidneys of mice and rats on a low-salt diet 209:255 Here, we investigated the cleavage state of the channel in the kidneys of mice and rats on a low-salt diet. 33522411 3 94 theme Fisher 317:322 arg1 cells 336:340 Fisher rat thyroid cells 317:340 Fisher rat thyroid cells 317:340 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 4 95 theme heterologous 482:493 arg1 system 495:500 the heterologous system 478:500 the heterologous system 478:500 To compare the peptides produced in the heterologous system with those in the mouse kidney, we treated both lysates with PNGaseF to remove N-linked glycosylation. 33522411 0 96 theme γENaC 18:22 arg1 state 9:13 Cleavage state 0:13 Cleavage state of γENaC in mouse and rat kidneys. 0:48 Cleavage state of γENaC in mouse and rat kidneys. 33522411 11 97 theme extracellular 1752:1764 arg1 protease 1794:1801 the extracellular protease channel-activating protease 1 1748:1803 the extracellular protease channel-activating protease 1 (prostasin) 1748:1815 This form appears to be identical in size with a subunit cleaved in vitro by the extracellular protease channel-activating protease 1 (prostasin). 33522411 11 97 theme extracellular 1752:1764 arg1 prostasin 1806:1814 prostasin 1806:1814 prostasin 1806:1814 This form appears to be identical in size with a subunit cleaved in vitro by the extracellular protease channel-activating protease 1 (prostasin). 33522411 9 98 theme lower 1228:1232 arg1 mass 1205:1208 an apparent molecular mass 1183:1208 an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form 1183:1266 Under these conditions, the major cleaved form in the rat kidney had an apparent molecular mass of 56 kDa, ∼4 kDa lower than that of the full-length form, consistent with excision of a short peptide by two proteolytic events. 33522411 8 99 theme nonreducing 1009:1019 arg1 gels 1021:1024 nonreducing gels 1009:1024 nonreducing gels 1009:1024 This was confirmed using nonreducing gels, in which the NH2- and COOH-terminal fragments of γENaC are linked by a disulfide bond. 33522411 6 100 theme cleaved 787:793 arg1 peptides 795:802 Similar cleaved peptides 779:802 Similar cleaved peptides 779:802 Similar cleaved peptides were observed in total and cell surface fractions of the rat kidney. 33522411 10 101 theme & 1506:1506 arg1 species 1381:1387 the most abundant γENaC species 1357:1387 the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet 1357:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 101 theme & 1506:1506 arg1 NOTEWORTHY 1508:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY 1457:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide 1457:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 102 dep NOTEWORTHY 1508:1517 arg1 identified 1527:1536 identified 1527:1536 have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide 1522:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 3 103 theme channel-activating 393:410 arg1 protease 412:419 the apical membrane-bound protease channel-activating protease 1 358:421 the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin) 358:439 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 3 103 theme channel-activating 393:410 arg1 CAP1 424:427 CAP1 424:427 CAP1; prostasin 424:438 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 10 104 from membrane 1403:1410 arg1 diet 1449:1452 a low-Na diet 1440:1452 a low-Na diet 1440:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 0 105 dep mouse 27:31 arg1 kidneys 41:47 kidneys 41:47 kidneys 41:47 Cleavage state of γENaC in mouse and rat kidneys. 33522411 3 106 theme thyroid 328:334 arg1 cells 336:340 Fisher rat thyroid cells 317:340 Fisher rat thyroid cells 317:340 We identified the cleaved species of channels expressed in Fisher rat thyroid cells by coexpressing the apical membrane-bound protease channel-activating protease 1 (CAP1; prostasin). 33522411 12 107 with consistent 1924:1933 arg1 excision 1944:1951 the excision 1940:1951 the excision of an inhibitory domain 1940:1975 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 10 108 theme aldosterone-dependent 1548:1568 arg1 peptide 1662:1668 a twice-cleaved peptide 1646:1668 a twice-cleaved peptide 1646:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 108 theme aldosterone-dependent 1548:1568 arg1 form 1578:1581 the major aldosterone-dependent cleaved form 1538:1581 the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney 1538:1641 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 109 theme abundant 1366:1373 arg1 species 1381:1387 the most abundant γENaC species 1357:1387 the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet 1357:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 109 theme abundant 1366:1373 arg1 NOTEWORTHY 1508:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY 1457:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide 1457:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 12 110 theme agents 1845:1850 arg1 absence 1825:1831 the absence 1821:1831 the absence of reducing agents 1821:1850 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 12 111 theme intact 1908:1913 arg1 subunit 1915:1921 the intact subunit 1904:1921 the intact subunit 1904:1921 In the absence of reducing agents, it has an overall molecular mass less than that of the intact subunit, consistent with the excision of an inhibitory domain. 33522411 10 112 theme form.NEW 1497:1504 arg1 species 1381:1387 the most abundant γENaC species 1357:1387 the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet 1357:1452 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 33522411 10 112 theme form.NEW 1497:1504 arg1 NOTEWORTHY 1508:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY 1457:1517 the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide 1457:1668 We conclude that the most abundant γENaC species in the apical membrane of rat and mouse kidneys on a low-Na diet is the twice-cleaved, presumably activated form.NEW & NOTEWORTHY We have identified the major aldosterone-dependent cleaved form of the epithelial Na channel (ENaC) γ subunit in the kidney as a twice-cleaved peptide. 35502904 6 0 theme CD164 926:930 arg1 CD164 926:930 CD164 926:930 CD164 926:930 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 6 0 theme CD164 926:930 arg1 domain 916:921 the cysteine-rich domain 898:921 the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region 898:1002 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 0 1 theme Human 39:43 arg1 Factor 84:89 an Essential Entry Factor 65:89 an Essential Entry Factor for Lymphocytic Choriomeningitis Virus 65:128 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 0 1 theme Human 39:43 arg1 CD164 56:60 Human Sialomucin CD164 39:60 Human Sialomucin CD164 39:60 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 4 2 theme functional 583:592 arg1 role 594:597 a functional role 581:597 a functional role 581:597 We identified and validated a variety of novel host factors that play a functional role in LCMV infection. 35502904 14 3 theme therapeutic 2443:2453 arg1 CD164 2364:2368 CD164 2364:2368 CD164 2364:2368 We demonstrated that CD164 is essential for LCMV entry into human cells and can serve as a possible therapeutic target for treatment of congenital infection. 35502904 14 3 theme therapeutic 2443:2453 arg1 target 2455:2460 a possible therapeutic target 2432:2460 a possible therapeutic target for treatment of congenital infection 2432:2498 We demonstrated that CD164 is essential for LCMV entry into human cells and can serve as a possible therapeutic target for treatment of congenital infection. 35502904 5 4 theme sialomucin 647:656 arg1 CD164 658:662 the sialomucin CD164 643:662 the sialomucin CD164 643:662 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 5 4 theme sialomucin 647:656 arg1 protein 702:708 a heavily glycosylated transmembrane protein 665:708 a heavily glycosylated transmembrane protein 665:708 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 10 5 theme congenital 1759:1768 arg1 infections 1770:1779 congenital infections 1759:1779 congenital infections 1759:1779 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 12 6 theme cell 1988:1991 arg1 molecule 2002:2009 a cell adhesion molecule 1986:2009 a cell adhesion molecule 1986:2009 For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. 35502904 12 6 theme cell 1988:1991 arg1 DAG1 2012:2015 DAG1 2012:2015 DAG1 2012:2015 For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. 35502904 2 7 theme LCMV 280:283 arg1 interactions 293:304 its interactions 289:304 its interactions with human host factors 289:328 However, our understanding of LCMV and its interactions with human host factors remains incomplete. 35502904 2 7 theme LCMV 280:283 arg1 understanding 263:275 our understanding 259:275 our understanding of LCMV 259:283 However, our understanding of LCMV and its interactions with human host factors remains incomplete. 35502904 1 8 theme well-studied 178:189 arg1 mammarenavirus 191:204 a well-studied mammarenavirus 176:204 a well-studied mammarenavirus that can be fatal in congenital infections 176:247 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 1 8 theme well-studied 178:189 arg1 virus 160:164 Lymphocytic choriomeningitis virus 131:164 Lymphocytic choriomeningitis virus (LCMV) 131:171 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 1 8 theme well-studied 178:189 arg1 fatal 218:222 fatal 218:222 fatal 218:222 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 6 9 theme entry 889:893 arg1 dependency 870:879 a dependency 868:879 a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region 868:1002 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 11 10 from study 1814:1818 arg1 field 1852:1856 the field 1848:1856 the field of immunology 1848:1870 Although frequently used in the study of persistent infections in the field of immunology, aspects of this virus's life cycle remain incomplete. 35502904 8 11 theme initial 1246:1252 arg1 site 1262:1265 an initial contact site 1243:1265 an initial contact site for pathogens within the placenta 1243:1299 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 7 12 theme CD164 1088:1092 arg1 expression 1094:1103 CD164 expression 1088:1103 CD164 expression 1088:1103 Given the documented role of LCMV with respect to transplacental human infections, CD164 expression was investigated in human placental tissue and placental cell lines. 35502904 2 13 theme host 317:320 arg1 factors 322:328 human host factors 311:328 human host factors 311:328 However, our understanding of LCMV and its interactions with human host factors remains incomplete. 35502904 7 14 theme placental 1131:1139 arg1 tissue 1141:1146 human placental tissue 1125:1146 human placental tissue 1125:1146 Given the documented role of LCMV with respect to transplacental human infections, CD164 expression was investigated in human placental tissue and placental cell lines. 35502904 12 15 theme viral 2068:2072 arg1 infection 2074:2082 residual viral infection 2059:2082 residual viral infection 2059:2082 For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. 35502904 5 16 from infection 731:739 arg1 types 827:831 several cell types 814:831 several cell types 814:831 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 5 17 with infection 731:739 arg1 mammarenaviruses 794:809 other hemorrhagic mammarenaviruses 776:809 multiple LCMV strains but not other hemorrhagic mammarenaviruses 746:809 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 5 17 with infection 731:739 arg1 strains 760:766 multiple LCMV strains 746:766 multiple LCMV strains but not other hemorrhagic mammarenaviruses 746:809 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 7 18 theme transplacental 1055:1068 arg1 infections 1076:1085 transplacental human infections 1055:1085 transplacental human infections 1055:1085 Given the documented role of LCMV with respect to transplacental human infections, CD164 expression was investigated in human placental tissue and placental cell lines. 35502904 1 19 from fatal 218:222 arg1 infections 238:247 congenital infections 227:247 congenital infections 227:247 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 8 20 theme cytotrophoblast 1220:1234 arg1 cells 1236:1240 the cytotrophoblast cells 1216:1240 the cytotrophoblast cells 1216:1240 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 6 21 theme N-linked 946:953 arg1 site 969:972 an N-linked glycosylation site 943:972 an N-linked glycosylation site at residue 104 in that region 943:1002 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 12 22 theme gene 2043:2046 arg1 knockout 2026:2033 knockout 2026:2033 knockout 2026:2033 For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. 35502904 11 23 theme persistent 1823:1832 arg1 infections 1834:1843 persistent infections 1823:1843 persistent infections in the field of immunology 1823:1870 Although frequently used in the study of persistent infections in the field of immunology, aspects of this virus's life cycle remain incomplete. 35502904 1 24 theme Lymphocytic 131:141 arg1 mammarenavirus 191:204 a well-studied mammarenavirus 176:204 a well-studied mammarenavirus that can be fatal in congenital infections 176:247 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 1 24 theme Lymphocytic 131:141 arg1 LCMV 167:170 LCMV 167:170 LCMV 167:170 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 1 24 theme Lymphocytic 131:141 arg1 virus 160:164 Lymphocytic choriomeningitis virus 131:164 Lymphocytic choriomeningitis virus (LCMV) 131:171 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 1 24 theme Lymphocytic 131:141 arg1 fatal 218:222 fatal 218:222 fatal 218:222 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 2 25 with understanding 263:275 arg1 factors 322:328 human host factors 311:328 human host factors 311:328 However, our understanding of LCMV and its interactions with human host factors remains incomplete. 35502904 0 26 theme Genome-Wide 0:10 arg1 Screen 21:26 Genome-Wide Knockout Screen 0:26 Genome-Wide Knockout Screen 0:26 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 5 27 theme transmembrane 688:700 arg1 CD164 658:662 the sialomucin CD164 643:662 the sialomucin CD164 643:662 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 5 27 theme transmembrane 688:700 arg1 protein 702:708 a heavily glycosylated transmembrane protein 665:708 a heavily glycosylated transmembrane protein 665:708 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 13 28 theme sialomucin 2262:2271 arg1 CD164 2273:2277 the sialomucin CD164 2258:2277 the sialomucin CD164 2258:2277 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 10 29 from infections 1770:1779 arg1 virus 1688:1692 IMPORTANCE Lymphocytic choriomeningitis virus 1648:1692 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) 1648:1699 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 29 from infections 1770:1779 arg1 fatal 1750:1754 fatal 1750:1754 fatal 1750:1754 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 29 from infections 1770:1779 arg1 mammarenavirus 1723:1736 a human-pathogenic mammarenavirus 1704:1736 a human-pathogenic mammarenavirus that can be fatal in congenital infections 1704:1779 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 1 30 theme choriomeningitis 143:158 arg1 mammarenavirus 191:204 a well-studied mammarenavirus 176:204 a well-studied mammarenavirus that can be fatal in congenital infections 176:247 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 1 30 theme choriomeningitis 143:158 arg1 LCMV 167:170 LCMV 167:170 LCMV 167:170 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 1 30 theme choriomeningitis 143:158 arg1 virus 160:164 Lymphocytic choriomeningitis virus 131:164 Lymphocytic choriomeningitis virus (LCMV) 131:171 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 1 30 theme choriomeningitis 143:158 arg1 fatal 218:222 fatal 218:222 fatal 218:222 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 8 31 theme LCMV 1306:1309 arg1 infection 1311:1319 LCMV infection 1306:1319 LCMV infection in placental cells 1306:1338 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 11 32 theme cycle 1902:1906 arg1 aspects 1873:1879 aspects 1873:1879 aspects of this virus's life cycle 1873:1906 Although frequently used in the study of persistent infections in the field of immunology, aspects of this virus's life cycle remain incomplete. 35502904 5 33 theme LCMV 755:758 arg1 strains 760:766 multiple LCMV strains 746:766 multiple LCMV strains but not other hemorrhagic mammarenaviruses 746:809 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 6 34 link N-linked 946:953 arg1 site 969:972 an N-linked glycosylation site 943:972 an N-linked glycosylation site at residue 104 in that region 943:1002 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 8 35 from site 1262:1265 arg1 cells 1334:1338 placental cells 1324:1338 placental cells 1324:1338 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 9 36 theme human 1519:1523 arg1 tissues 1525:1531 human tissues 1519:1531 human tissues 1519:1531 Together, this study identifies novel factors associated with LCMV infection of human tissues and highlights the importance of CD164, a sialomucin that previously had not been associated with viral infection. 35502904 7 37 theme LCMV 1034:1037 arg1 role 1026:1029 the documented role 1011:1029 the documented role of LCMV with respect to transplacental human infections 1011:1085 Given the documented role of LCMV with respect to transplacental human infections, CD164 expression was investigated in human placental tissue and placental cell lines. 35502904 0 38 theme Entry 78:82 arg1 Factor 84:89 an Essential Entry Factor 65:89 an Essential Entry Factor for Lymphocytic Choriomeningitis Virus 65:128 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 0 38 theme Entry 78:82 arg1 CD164 56:60 Human Sialomucin CD164 39:60 Human Sialomucin CD164 39:60 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 10 39 theme Lymphocytic 1659:1669 arg1 virus 1688:1692 IMPORTANCE Lymphocytic choriomeningitis virus 1648:1692 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) 1648:1699 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 39 theme Lymphocytic 1659:1669 arg1 fatal 1750:1754 fatal 1750:1754 fatal 1750:1754 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 39 theme Lymphocytic 1659:1669 arg1 mammarenavirus 1723:1736 a human-pathogenic mammarenavirus 1704:1736 a human-pathogenic mammarenavirus that can be fatal in congenital infections 1704:1779 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 39 theme Lymphocytic 1659:1669 arg1 LCMV 1695:1698 LCMV 1695:1698 LCMV 1695:1698 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 0 40 theme Choriomeningitis 107:122 arg1 Virus 124:128 Lymphocytic Choriomeningitis Virus 95:128 Lymphocytic Choriomeningitis Virus 95:128 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 7 41 theme documented 1015:1024 arg1 role 1026:1029 the documented role 1011:1029 the documented role of LCMV with respect to transplacental human infections 1011:1085 Given the documented role of LCMV with respect to transplacental human infections, CD164 expression was investigated in human placental tissue and placental cell lines. 35502904 0 42 theme Sialomucin 45:54 arg1 Factor 84:89 an Essential Entry Factor 65:89 an Essential Entry Factor for Lymphocytic Choriomeningitis Virus 65:128 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 0 42 theme Sialomucin 45:54 arg1 CD164 56:60 Human Sialomucin CD164 39:60 Human Sialomucin CD164 39:60 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 0 43 theme Essential 68:76 arg1 Factor 84:89 an Essential Entry Factor 65:89 an Essential Entry Factor for Lymphocytic Choriomeningitis Virus 65:128 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 0 43 theme Essential 68:76 arg1 CD164 56:60 Human Sialomucin CD164 39:60 Human Sialomucin CD164 39:60 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 3 44 theme knockout 446:453 arg1 screen 455:460 a genome-wide CRISPR knockout screen 425:460 a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line 425:508 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 5 45 theme several 814:820 arg1 types 827:831 several cell types 814:831 several cell types 814:831 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 3 46 theme LCMV 384:387 arg1 infection 389:397 LCMV infection 384:397 LCMV infection 384:397 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 4 47 theme host 558:561 arg1 factors 563:569 novel host factors 552:569 novel host factors that play a functional role in LCMV infection 552:615 We identified and validated a variety of novel host factors that play a functional role in LCMV infection. 35502904 8 48 theme monoclonal 1372:1381 arg1 antibody 1383:1390 a monoclonal antibody 1370:1390 a monoclonal antibody specific to the cysteine-rich domain of CD164 1370:1436 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 13 49 theme host 2199:2202 arg1 CD164 2273:2277 the sialomucin CD164 2258:2277 the sialomucin CD164 2258:2277 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 13 49 theme host 2199:2202 arg1 factors 2204:2210 host factors 2199:2210 host factors 2199:2210 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 6 50 theme LCMV 884:887 arg1 entry 889:893 LCMV entry 884:893 LCMV entry 884:893 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 3 51 theme genome-wide 427:437 arg1 screen 455:460 a genome-wide CRISPR knockout screen 425:460 a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line 425:508 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 8 52 theme specific 1392:1399 arg1 antibody 1383:1390 a monoclonal antibody 1370:1390 a monoclonal antibody specific to the cysteine-rich domain of CD164 1370:1436 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 5 53 theme other 776:780 arg1 mammarenaviruses 794:809 other hemorrhagic mammarenaviruses 776:809 multiple LCMV strains but not other hemorrhagic mammarenaviruses 746:809 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 7 54 theme cell 1162:1165 arg1 lines 1167:1171 placental cell lines 1152:1171 placental cell lines 1152:1171 Given the documented role of LCMV with respect to transplacental human infections, CD164 expression was investigated in human placental tissue and placental cell lines. 35502904 14 55 theme human 2403:2407 arg1 cells 2409:2413 human cells 2403:2413 human cells 2403:2413 We demonstrated that CD164 is essential for LCMV entry into human cells and can serve as a possible therapeutic target for treatment of congenital infection. 35502904 10 56 theme human-pathogenic 1706:1721 arg1 virus 1688:1692 IMPORTANCE Lymphocytic choriomeningitis virus 1648:1692 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) 1648:1699 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 56 theme human-pathogenic 1706:1721 arg1 fatal 1750:1754 fatal 1750:1754 fatal 1750:1754 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 56 theme human-pathogenic 1706:1721 arg1 mammarenavirus 1723:1736 a human-pathogenic mammarenavirus 1704:1736 a human-pathogenic mammarenavirus that can be fatal in congenital infections 1704:1779 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 14 57 theme congenital 2479:2488 arg1 infection 2490:2498 congenital infection 2479:2498 congenital infection 2479:2498 We demonstrated that CD164 is essential for LCMV entry into human cells and can serve as a possible therapeutic target for treatment of congenital infection. 35502904 3 58 theme lung 485:488 arg1 line 505:508 a human lung adenocarcinoma line 477:508 a human lung adenocarcinoma line 477:508 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 3 58 theme lung 485:488 arg1 cells 470:474 A549 cells 465:474 A549 cells 465:474 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 1 59 theme congenital 227:236 arg1 infections 238:247 congenital infections 227:247 congenital infections 227:247 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 6 60 theme Further 834:840 arg1 characterization 842:857 Further characterization 834:857 Further characterization 834:857 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 13 61 theme viral 2326:2330 arg1 infection 2332:2340 viral infection 2326:2340 viral infection 2326:2340 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 4 62 theme LCMV 602:605 arg1 infection 607:615 LCMV infection 602:615 LCMV infection 602:615 We identified and validated a variety of novel host factors that play a functional role in LCMV infection. 35502904 8 63 theme CD164 1432:1436 arg1 domain 1422:1427 the cysteine-rich domain 1404:1427 the cysteine-rich domain of CD164 1404:1436 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 8 63 theme CD164 1432:1436 arg1 CD164 1432:1436 CD164 1432:1436 CD164 1432:1436 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 3 64 from screen 455:460 arg1 line 505:508 a human lung adenocarcinoma line 477:508 a human lung adenocarcinoma line 477:508 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 3 64 from screen 455:460 arg1 cells 470:474 A549 cells 465:474 A549 cells 465:474 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 12 65 theme adhesion 1993:2000 arg1 molecule 2002:2009 a cell adhesion molecule 1986:2009 a cell adhesion molecule 1986:2009 For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. 35502904 12 65 theme adhesion 1993:2000 arg1 DAG1 2012:2015 DAG1 2012:2015 DAG1 2012:2015 For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. 35502904 9 66 theme viral 1631:1635 arg1 infection 1637:1645 viral infection 1631:1645 viral infection 1631:1645 Together, this study identifies novel factors associated with LCMV infection of human tissues and highlights the importance of CD164, a sialomucin that previously had not been associated with viral infection. 35502904 7 67 theme human 1125:1129 arg1 tissue 1141:1146 human placental tissue 1125:1146 human placental tissue 1125:1146 Given the documented role of LCMV with respect to transplacental human infections, CD164 expression was investigated in human placental tissue and placental cell lines. 35502904 14 68 theme possible 2434:2441 arg1 CD164 2364:2368 CD164 2364:2368 CD164 2364:2368 We demonstrated that CD164 is essential for LCMV entry into human cells and can serve as a possible therapeutic target for treatment of congenital infection. 35502904 14 68 theme possible 2434:2441 arg1 target 2455:2460 a possible therapeutic target 2432:2460 a possible therapeutic target for treatment of congenital infection 2432:2498 We demonstrated that CD164 is essential for LCMV entry into human cells and can serve as a possible therapeutic target for treatment of congenital infection. 35502904 11 69 from infections 1834:1843 arg1 field 1852:1856 the field 1848:1856 the field of immunology 1848:1870 Although frequently used in the study of persistent infections in the field of immunology, aspects of this virus's life cycle remain incomplete. 35502904 5 70 theme CD164 658:662 arg1 knockout 631:638 knockout 631:638 knockout 631:638 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 6 71 gly glycosylation 955:967 arg2 residue 977:983 residue 104 977:987 residue 104 977:987 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 6 71 gly glycosylation 955:967 arg2 site 969:972 an N-linked glycosylation site 943:972 an N-linked glycosylation site at residue 104 in that region 943:1002 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 6 72 theme cysteine-rich 902:914 arg1 CD164 926:930 CD164 926:930 CD164 926:930 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 6 72 theme cysteine-rich 902:914 arg1 domain 916:921 the cysteine-rich domain 898:921 the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region 898:1002 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 13 73 theme successful 2226:2235 arg1 infection 2237:2245 successful infection 2226:2245 successful infection 2226:2245 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 11 74 theme immunology 1861:1870 arg1 field 1852:1856 the field 1848:1856 the field of immunology 1848:1870 Although frequently used in the study of persistent infections in the field of immunology, aspects of this virus's life cycle remain incomplete. 35502904 6 75 from dependency 870:879 arg1 CD164 926:930 CD164 926:930 CD164 926:930 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 6 75 from dependency 870:879 arg1 domain 916:921 the cysteine-rich domain 898:921 the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region 898:1002 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 12 76 theme additional 2099:2108 arg1 receptors 2110:2118 additional receptors 2099:2118 additional receptors 2099:2118 For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. 35502904 7 77 theme human 1070:1074 arg1 infections 1076:1085 transplacental human infections 1055:1085 transplacental human infections 1055:1085 Given the documented role of LCMV with respect to transplacental human infections, CD164 expression was investigated in human placental tissue and placental cell lines. 35502904 2 78 theme human 311:315 arg1 factors 322:328 human host factors 311:328 human host factors 311:328 However, our understanding of LCMV and its interactions with human host factors remains incomplete. 35502904 8 79 theme contact 1254:1260 arg1 site 1262:1265 an initial contact site 1243:1265 an initial contact site for pathogens within the placenta 1243:1299 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 9 80 theme novel 1471:1475 arg1 factors 1477:1483 novel factors 1471:1483 novel factors associated with LCMV infection of human tissues 1471:1531 Together, this study identifies novel factors associated with LCMV infection of human tissues and highlights the importance of CD164, a sialomucin that previously had not been associated with viral infection. 35502904 6 81 theme glycosylation 955:967 arg1 site 969:972 an N-linked glycosylation site 943:972 an N-linked glycosylation site at residue 104 in that region 943:1002 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 12 82 theme viral 1946:1950 arg1 entry 1952:1956 viral entry 1946:1956 viral entry 1946:1956 For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. 35502904 11 83 theme infections 1834:1843 arg1 study 1814:1818 the study 1810:1818 the study of persistent infections in the field of immunology 1810:1870 Although frequently used in the study of persistent infections in the field of immunology, aspects of this virus's life cycle remain incomplete. 35502904 5 84 theme glycosylated 675:686 arg1 CD164 658:662 the sialomucin CD164 643:662 the sialomucin CD164 643:662 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 5 84 theme glycosylated 675:686 arg1 protein 702:708 a heavily glycosylated transmembrane protein 665:708 a heavily glycosylated transmembrane protein 665:708 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 9 85 theme LCMV 1501:1504 arg1 infection 1506:1514 LCMV infection 1501:1514 LCMV infection of human tissues 1501:1531 Together, this study identifies novel factors associated with LCMV infection of human tissues and highlights the importance of CD164, a sialomucin that previously had not been associated with viral infection. 35502904 10 86 from fatal 1750:1754 arg1 infections 1770:1779 congenital infections 1759:1779 congenital infections 1759:1779 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 5 87 theme multiple 746:753 arg1 strains 760:766 multiple LCMV strains 746:766 multiple LCMV strains but not other hemorrhagic mammarenaviruses 746:809 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 13 88 theme important 2212:2220 arg1 CD164 2273:2277 the sialomucin CD164 2258:2277 the sialomucin CD164 2258:2277 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 13 88 theme important 2212:2220 arg1 factors 2204:2210 host factors 2199:2210 host factors 2199:2210 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 2 89 with interactions 293:304 arg1 factors 322:328 human host factors 311:328 human host factors 311:328 However, our understanding of LCMV and its interactions with human host factors remains incomplete. 35502904 9 90 theme tissues 1525:1531 arg1 infection 1506:1514 LCMV infection 1501:1514 LCMV infection of human tissues 1501:1531 Together, this study identifies novel factors associated with LCMV infection of human tissues and highlights the importance of CD164, a sialomucin that previously had not been associated with viral infection. 35502904 5 91 gly glycosylated 675:686 arg1 CD164 658:662 the sialomucin CD164 643:662 the sialomucin CD164 643:662 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 5 91 gly glycosylated 675:686 arg1 protein 702:708 a heavily glycosylated transmembrane protein 665:708 a heavily glycosylated transmembrane protein 665:708 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 0 92 theme Lymphocytic 95:105 arg1 Virus 124:128 Lymphocytic Choriomeningitis Virus 95:128 Lymphocytic Choriomeningitis Virus 95:128 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 1 93 from infections 238:247 arg1 mammarenavirus 191:204 a well-studied mammarenavirus 176:204 a well-studied mammarenavirus that can be fatal in congenital infections 176:247 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 1 93 from infections 238:247 arg1 virus 160:164 Lymphocytic choriomeningitis virus 131:164 Lymphocytic choriomeningitis virus (LCMV) 131:171 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 1 93 from infections 238:247 arg1 fatal 218:222 fatal 218:222 fatal 218:222 Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. 35502904 8 94 theme placental 1324:1332 arg1 cells 1334:1338 placental cells 1324:1338 placental cells 1324:1338 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 12 95 theme residual 2059:2066 arg1 infection 2074:2082 residual viral infection 2059:2082 residual viral infection 2059:2082 For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. 35502904 3 96 theme host 356:359 arg1 determinants 361:372 host determinants 356:372 host determinants affecting LCMV infection 356:397 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 11 97 from field 1852:1856 arg1 study 1814:1818 the study 1810:1818 the study of persistent infections in the field of immunology 1810:1870 Although frequently used in the study of persistent infections in the field of immunology, aspects of this virus's life cycle remain incomplete. 35502904 10 98 theme IMPORTANCE 1648:1657 arg1 virus 1688:1692 IMPORTANCE Lymphocytic choriomeningitis virus 1648:1692 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) 1648:1699 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 98 theme IMPORTANCE 1648:1657 arg1 fatal 1750:1754 fatal 1750:1754 fatal 1750:1754 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 98 theme IMPORTANCE 1648:1657 arg1 mammarenavirus 1723:1736 a human-pathogenic mammarenavirus 1704:1736 a human-pathogenic mammarenavirus that can be fatal in congenital infections 1704:1779 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 98 theme IMPORTANCE 1648:1657 arg1 LCMV 1695:1698 LCMV 1695:1698 LCMV 1695:1698 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 0 99 theme Knockout 12:19 arg1 Screen 21:26 Genome-Wide Knockout Screen 0:26 Genome-Wide Knockout Screen 0:26 Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus. 35502904 8 100 from infection 1311:1319 arg1 cells 1334:1338 placental cells 1324:1338 placental cells 1324:1338 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 9 101 theme CD164 1566:1570 arg1 importance 1552:1561 the importance 1548:1561 the importance of CD164, a sialomucin that previously had not been associated with viral infection 1548:1645 Together, this study identifies novel factors associated with LCMV infection of human tissues and highlights the importance of CD164, a sialomucin that previously had not been associated with viral infection. 35502904 4 102 theme factors 563:569 arg1 factors 563:569 novel host factors 552:569 novel host factors that play a functional role in LCMV infection 552:615 We identified and validated a variety of novel host factors that play a functional role in LCMV infection. 35502904 4 102 theme factors 563:569 arg1 variety 541:547 a variety 539:547 a variety of novel host factors that play a functional role in LCMV infection 539:615 We identified and validated a variety of novel host factors that play a functional role in LCMV infection. 35502904 11 103 theme life 1897:1900 arg1 cycle 1902:1906 this virus's life cycle 1884:1906 this virus's life cycle 1884:1906 Although frequently used in the study of persistent infections in the field of immunology, aspects of this virus's life cycle remain incomplete. 35502904 5 104 theme cell 822:825 arg1 types 827:831 several cell types 814:831 several cell types 814:831 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 6 105 from site 969:972 arg1 region 997:1002 that region 992:1002 that region 992:1002 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 3 106 theme human 479:483 arg1 line 505:508 a human lung adenocarcinoma line 477:508 a human lung adenocarcinoma line 477:508 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 3 106 theme human 479:483 arg1 cells 470:474 A549 cells 465:474 A549 cells 465:474 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 7 107 theme placental 1152:1160 arg1 lines 1167:1171 placental cell lines 1152:1171 placental cell lines 1152:1171 Given the documented role of LCMV with respect to transplacental human infections, CD164 expression was investigated in human placental tissue and placental cell lines. 35502904 13 108 theme factors 2204:2210 arg1 significance 2148:2159 The significance 2144:2159 The significance of our study 2144:2172 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 13 108 theme factors 2204:2210 arg1 identification 2181:2194 the identification 2177:2194 the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection 2177:2340 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 3 109 theme CRISPR 439:444 arg1 screen 455:460 a genome-wide CRISPR knockout screen 425:460 a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line 425:508 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 6 110 from residue 977:983 arg1 site 969:972 an N-linked glycosylation site 943:972 an N-linked glycosylation site at residue 104 in that region 943:1002 Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. 35502904 10 111 theme choriomeningitis 1671:1686 arg1 virus 1688:1692 IMPORTANCE Lymphocytic choriomeningitis virus 1648:1692 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) 1648:1699 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 111 theme choriomeningitis 1671:1686 arg1 fatal 1750:1754 fatal 1750:1754 fatal 1750:1754 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 111 theme choriomeningitis 1671:1686 arg1 mammarenavirus 1723:1736 a human-pathogenic mammarenavirus 1704:1736 a human-pathogenic mammarenavirus that can be fatal in congenital infections 1704:1779 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 10 111 theme choriomeningitis 1671:1686 arg1 LCMV 1695:1698 LCMV 1695:1698 LCMV 1695:1698 IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. 35502904 5 112 theme hemorrhagic 782:792 arg1 mammarenaviruses 794:809 other hemorrhagic mammarenaviruses 776:809 multiple LCMV strains but not other hemorrhagic mammarenaviruses 746:809 Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. 35502904 13 113 theme study 2168:2172 arg1 significance 2148:2159 The significance 2144:2159 The significance of our study 2144:2172 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 13 113 theme study 2168:2172 arg1 identification 2181:2194 the identification 2177:2194 the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection 2177:2340 The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. 35502904 14 114 theme infection 2490:2498 arg1 treatment 2466:2474 treatment 2466:2474 treatment of congenital infection 2466:2498 We demonstrated that CD164 is essential for LCMV entry into human cells and can serve as a possible therapeutic target for treatment of congenital infection. 35502904 4 115 theme novel 552:556 arg1 factors 563:569 novel host factors 552:569 novel host factors that play a functional role in LCMV infection 552:615 We identified and validated a variety of novel host factors that play a functional role in LCMV infection. 35502904 8 116 theme cysteine-rich 1408:1420 arg1 domain 1422:1427 the cysteine-rich domain 1404:1427 the cysteine-rich domain of CD164 1404:1436 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 8 116 theme cysteine-rich 1408:1420 arg1 CD164 1432:1436 CD164 1432:1436 CD164 1432:1436 CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. 35502904 14 117 theme LCMV 2387:2390 arg1 entry 2392:2396 LCMV entry 2387:2396 LCMV entry into human cells 2387:2413 We demonstrated that CD164 is essential for LCMV entry into human cells and can serve as a possible therapeutic target for treatment of congenital infection. 35502904 3 118 theme adenocarcinoma 490:503 arg1 line 505:508 a human lung adenocarcinoma line 477:508 a human lung adenocarcinoma line 477:508 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 3 118 theme adenocarcinoma 490:503 arg1 cells 470:474 A549 cells 465:474 A549 cells 465:474 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 3 119 theme A549 465:468 arg1 line 505:508 a human lung adenocarcinoma line 477:508 a human lung adenocarcinoma line 477:508 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 3 119 theme A549 465:468 arg1 cells 470:474 A549 cells 465:474 A549 cells 465:474 Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. 35502904 12 120 theme cell 2132:2135 arg1 entry 2137:2141 cell entry 2132:2141 cell entry 2132:2141 For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. 34908252 4 0 theme confirmed 465:473 arg1 TAs 475:477 biopsy confirmed TAs 458:477 biopsy confirmed TAs 458:477 METHODS Thirty-three patients including two family members with biopsy confirmed TAs were collected. 34908252 1 1 with myopathies 134:143 arg1 TAs 170:172 TAs 170:172 TAs 170:172 OBJECTIVE A group of genes have been reported to be associated with myopathies with tubular aggregates (TAs). 34908252 1 1 with myopathies 134:143 arg1 aggregates 158:167 tubular aggregates 150:167 tubular aggregates (TAs) 150:173 OBJECTIVE A group of genes have been reported to be associated with myopathies with tubular aggregates (TAs). 34908252 13 2 theme signalling 1551:1560 arg1 pathway 1562:1568 calcium signalling pathway 1543:1568 calcium signalling pathway 1543:1568 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 2 3 with cases 181:185 arg1 TAs 192:194 TAs 192:194 TAs 192:194 Many cases with TAs still lack of genetic clarification. 34908252 13 4 theme related 1530:1536 arg1 causes 1626:1631 the main genetic causes 1609:1631 the main genetic causes of myopathies with TAs 1609:1654 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 13 4 theme related 1530:1536 arg1 genes 1524:1528 genes 1524:1528 genes related with calcium signalling pathway and N-linked glycosylation pathway 1524:1603 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 12 5 theme genotypic 1426:1434 arg1 spectrums 1436:1444 the phenotypic and genotypic spectrums 1407:1444 the phenotypic and genotypic spectrums of myopathies with TAs 1407:1467 INTERPRETATION This study expands the phenotypic and genotypic spectrums of myopathies with TAs. 34908252 3 6 theme cases 286:290 arg1 background 272:281 the genetic background 260:281 the genetic background of cases with TAs 260:299 This study aims to explore the genetic background of cases with TAs in order to improve our knowledge of the pathogenesis of these rare pathological structures. 34908252 5 7 theme candidate 569:577 arg1 strategy 591:598 a candidate gene search strategy 567:598 a candidate gene search strategy 567:598 Whole-exome sequencing was performed on 31 unrelated index patients and a candidate gene search strategy was conducted. 34908252 7 8 theme protein 842:848 arg1 levels 861:866 protein expression levels 842:866 protein expression levels 842:866 The wild-type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. 34908252 7 9 theme ALG14 719:723 arg1 p.Ala11Thr 705:714 the mutant p.Ala11Thr 694:714 the mutant p.Ala11Thr of ALG14 694:723 The wild-type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. 34908252 8 10 from variants 961:968 arg1 ORAI1 980:984 ORAI1 980:984 ORAI1 980:984 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 8 10 from variants 961:968 arg1 PGAM2 987:991 PGAM2 987:991 PGAM2 987:991 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 8 10 from variants 961:968 arg1 ALG14 1011:1015 ALG14 1011:1015 ALG14 1011:1015 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 8 10 from variants 961:968 arg1 STIM1 973:977 STIM1 973:977 STIM1 973:977 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 8 10 from variants 961:968 arg1 SCN4A 994:998 SCN4A 994:998 SCN4A 994:998 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 8 10 from variants 961:968 arg1 CASQ1 1001:1005 CASQ1 1001:1005 CASQ1 1001:1005 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 5 11 theme gene 579:582 arg1 strategy 591:598 a candidate gene search strategy 567:598 a candidate gene search strategy 567:598 Whole-exome sequencing was performed on 31 unrelated index patients and a candidate gene search strategy was conducted. 34908252 13 12 theme previous 1499:1506 arg1 hypothesis 1508:1517 previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs 1499:1654 previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs 1499:1654 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 7 13 theme expression 850:859 arg1 levels 861:866 protein expression levels 842:866 protein expression levels 842:866 The wild-type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. 34908252 7 14 theme mutant 698:703 arg1 p.Ala11Thr 705:714 the mutant p.Ala11Thr 694:714 the mutant p.Ala11Thr of ALG14 694:723 The wild-type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. 34908252 13 15 theme myopathies 1636:1645 arg1 causes 1626:1631 the main genetic causes 1609:1631 the main genetic causes of myopathies with TAs 1609:1654 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 13 15 theme myopathies 1636:1645 arg1 genes 1524:1528 genes 1524:1528 genes related with calcium signalling pathway and N-linked glycosylation pathway 1524:1603 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 5 16 theme search 584:589 arg1 strategy 591:598 a candidate gene search strategy 567:598 a candidate gene search strategy 567:598 Whole-exome sequencing was performed on 31 unrelated index patients and a candidate gene search strategy was conducted. 34908252 4 17 with members 445:451 arg1 TAs 475:477 biopsy confirmed TAs 458:477 biopsy confirmed TAs 458:477 METHODS Thirty-three patients including two family members with biopsy confirmed TAs were collected. 34908252 10 18 theme Western 1119:1125 arg1 analysis 1132:1139 Western blot analysis 1119:1139 Western blot analysis 1119:1139 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 4 19 theme family 438:443 arg1 members 445:451 two family members 434:451 two family members with biopsy confirmed TAs 434:477 METHODS Thirty-three patients including two family members with biopsy confirmed TAs were collected. 34908252 8 20 dep RESULTS 869:875 arg1 % 899:899 33% 897:899 33% 897:899 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 8 20 dep RESULTS 869:875 arg1 cases 890:894 Eleven index cases 877:894 RESULTS Eleven index cases (33%) 869:900 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 13 21 with related 1530:1536 arg1 pathway 1597:1603 N-linked glycosylation pathway 1574:1603 N-linked glycosylation pathway 1574:1603 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 13 21 with related 1530:1536 arg1 pathway 1562:1568 calcium signalling pathway 1543:1568 calcium signalling pathway 1543:1568 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 1 22 theme tubular 150:156 arg1 TAs 170:172 TAs 170:172 TAs 170:172 OBJECTIVE A group of genes have been reported to be associated with myopathies with tubular aggregates (TAs). 34908252 1 22 theme tubular 150:156 arg1 aggregates 158:167 tubular aggregates 150:167 tubular aggregates (TAs) 150:173 OBJECTIVE A group of genes have been reported to be associated with myopathies with tubular aggregates (TAs). 34908252 0 23 from myopathies 30:39 arg1 common 20:25 common 20:25 common 20:25 Genetic defects are common in myopathies with tubular aggregates. 34908252 5 24 theme index 548:552 arg1 patients 554:561 31 unrelated index patients 535:561 31 unrelated index patients 535:561 Whole-exome sequencing was performed on 31 unrelated index patients and a candidate gene search strategy was conducted. 34908252 12 25 theme myopathies 1449:1458 arg1 spectrums 1436:1444 the phenotypic and genotypic spectrums 1407:1444 the phenotypic and genotypic spectrums of myopathies with TAs 1407:1467 INTERPRETATION This study expands the phenotypic and genotypic spectrums of myopathies with TAs. 34908252 10 26 theme protein 1177:1183 arg1 expression 1157:1166 the expression 1153:1166 the expression of ALG14 protein 1153:1183 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 9 27 from c.1333G>C 1074:1082 arg1 STIM1 1060:1064 STIM1 1060:1064 STIM1 1060:1064 Among them, the c.764A>T (p.Glu255Val) in STIM1 and the c.1333G>C (p.Val445Leu) in SCN4A were novel. 34908252 9 27 from c.1333G>C 1074:1082 arg1 SCN4A 1101:1105 SCN4A 1101:1105 SCN4A 1101:1105 Among them, the c.764A>T (p.Glu255Val) in STIM1 and the c.1333G>C (p.Val445Leu) in SCN4A were novel. 34908252 8 28 theme pathogenic 950:959 arg1 variants 961:968 pathogenic variants 950:968 pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14 950:1015 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 8 29 theme index 884:888 arg1 % 899:899 33% 897:899 33% 897:899 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 8 29 theme index 884:888 arg1 cases 890:894 Eleven index cases 877:894 RESULTS Eleven index cases (33%) 869:900 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 10 30 theme ALG14 1171:1175 arg1 protein 1177:1183 ALG14 protein 1171:1183 ALG14 protein 1171:1183 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 3 31 theme pathological 369:380 arg1 structures 382:391 these rare pathological structures 358:391 these rare pathological structures 358:391 This study aims to explore the genetic background of cases with TAs in order to improve our knowledge of the pathogenesis of these rare pathological structures. 34908252 0 32 theme Genetic 0:6 arg1 defects 8:14 Genetic defects 0:14 Genetic defects 0:14 Genetic defects are common in myopathies with tubular aggregates. 34908252 13 33 theme main 1613:1616 arg1 causes 1626:1631 the main genetic causes 1609:1631 the main genetic causes of myopathies with TAs 1609:1654 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 13 33 theme main 1613:1616 arg1 genes 1524:1528 genes 1524:1528 genes related with calcium signalling pathway and N-linked glycosylation pathway 1524:1603 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 8 34 theme pathogenic 921:930 arg1 variant 932:938 pathogenic variant 921:938 pathogenic variant 921:938 RESULTS Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. 34908252 7 35 theme blot 802:805 arg1 analysis 807:814 western blot analysis 794:814 western blot analysis 794:814 The wild-type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. 34908252 3 36 with background 272:281 arg1 TAs 297:299 TAs 297:299 TAs 297:299 This study aims to explore the genetic background of cases with TAs in order to improve our knowledge of the pathogenesis of these rare pathological structures. 34908252 11 37 from TAs 1321:1323 arg1 patients 1328:1335 patients 1328:1335 patients with complex multisystem disorders 1328:1370 The ALG14 variants might be associated with TAs in patients with complex multisystem disorders. 34908252 10 38 theme wild 1266:1269 arg1 type 1271:1274 wild type 1266:1274 wild type 1266:1274 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 1 39 theme genes 87:91 arg1 genes 87:91 genes 87:91 genes 87:91 OBJECTIVE A group of genes have been reported to be associated with myopathies with tubular aggregates (TAs). 34908252 1 39 theme genes 87:91 arg1 group 78:82 A group 76:82 A group of genes 76:91 OBJECTIVE A group of genes have been reported to be associated with myopathies with tubular aggregates (TAs). 34908252 11 40 theme multisystem 1350:1360 arg1 disorders 1362:1370 complex multisystem disorders 1342:1370 complex multisystem disorders 1342:1370 The ALG14 variants might be associated with TAs in patients with complex multisystem disorders. 34908252 13 41 link N-linked 1574:1581 arg1 pathway 1597:1603 N-linked glycosylation pathway 1574:1603 N-linked glycosylation pathway 1574:1603 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 13 42 theme genetic 1618:1624 arg1 causes 1626:1631 the main genetic causes 1609:1631 the main genetic causes of myopathies with TAs 1609:1654 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 13 42 theme genetic 1618:1624 arg1 genes 1524:1528 genes 1524:1528 genes related with calcium signalling pathway and N-linked glycosylation pathway 1524:1603 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 11 43 with patients 1328:1335 arg1 disorders 1362:1370 complex multisystem disorders 1342:1370 complex multisystem disorders 1342:1370 The ALG14 variants might be associated with TAs in patients with complex multisystem disorders. 34908252 7 44 theme western 794:800 arg1 analysis 807:814 western blot analysis 794:814 western blot analysis 794:814 The wild-type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. 34908252 6 45 theme Sanger 657:662 arg1 sequencing 664:673 Sanger sequencing 657:673 Sanger sequencing 657:673 The identified variants were confirmed by Sanger sequencing. 34908252 10 46 theme mutant 1213:1218 arg1 cells 1233:1237 the mutant ALG14 HEK293 cells 1209:1237 the mutant ALG14 HEK293 cells (p.Ala11Thr) 1209:1250 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 10 46 theme mutant 1213:1218 arg1 p.Ala11Thr 1240:1249 p.Ala11Thr 1240:1249 p.Ala11Thr 1240:1249 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 13 47 theme N-linked 1574:1581 arg1 pathway 1597:1603 N-linked glycosylation pathway 1574:1603 N-linked glycosylation pathway 1574:1603 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 4 48 theme Thirty-three 402:413 arg1 patients 415:422 Thirty-three patients 402:422 METHODS Thirty-three patients including two family members with biopsy confirmed TAs 394:477 METHODS Thirty-three patients including two family members with biopsy confirmed TAs were collected. 34908252 4 48 theme Thirty-three 402:413 arg1 members 445:451 two family members 434:451 two family members with biopsy confirmed TAs 434:477 METHODS Thirty-three patients including two family members with biopsy confirmed TAs were collected. 34908252 3 49 theme structures 382:391 arg1 pathogenesis 342:353 the pathogenesis 338:353 the pathogenesis of these rare pathological structures 338:391 This study aims to explore the genetic background of cases with TAs in order to improve our knowledge of the pathogenesis of these rare pathological structures. 34908252 3 50 theme rare 364:367 arg1 structures 382:391 these rare pathological structures 358:391 these rare pathological structures 358:391 This study aims to explore the genetic background of cases with TAs in order to improve our knowledge of the pathogenesis of these rare pathological structures. 34908252 12 51 with myopathies 1449:1458 arg1 TAs 1465:1467 TAs 1465:1467 TAs 1465:1467 INTERPRETATION This study expands the phenotypic and genotypic spectrums of myopathies with TAs. 34908252 12 52 theme phenotypic 1411:1420 arg1 spectrums 1436:1444 the phenotypic and genotypic spectrums 1407:1444 the phenotypic and genotypic spectrums of myopathies with TAs 1407:1467 INTERPRETATION This study expands the phenotypic and genotypic spectrums of myopathies with TAs. 34908252 9 53 from c.764A>T 1034:1041 arg1 STIM1 1060:1064 STIM1 1060:1064 STIM1 1060:1064 Among them, the c.764A>T (p.Glu255Val) in STIM1 and the c.1333G>C (p.Val445Leu) in SCN4A were novel. 34908252 9 53 from c.764A>T 1034:1041 arg1 SCN4A 1101:1105 SCN4A 1101:1105 SCN4A 1101:1105 Among them, the c.764A>T (p.Glu255Val) in STIM1 and the c.1333G>C (p.Val445Leu) in SCN4A were novel. 34908252 12 54 dep expands 1399:1405 arg1 INTERPRETATION 1373:1386 INTERPRETATION 1373:1386 INTERPRETATION 1373:1386 INTERPRETATION This study expands the phenotypic and genotypic spectrums of myopathies with TAs. 34908252 7 55 theme kidney 763:768 arg1 HEK293 781:786 HEK293 781:786 HEK293 781:786 The wild-type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. 34908252 7 55 theme kidney 763:768 arg1 cells 774:778 human embryonic kidney 293 cells 747:778 human embryonic kidney 293 cells (HEK293) 747:787 The wild-type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. 34908252 3 56 theme pathogenesis 342:353 arg1 knowledge 325:333 our knowledge 321:333 our knowledge of the pathogenesis of these rare pathological structures 321:391 This study aims to explore the genetic background of cases with TAs in order to improve our knowledge of the pathogenesis of these rare pathological structures. 34908252 3 57 theme genetic 264:270 arg1 background 272:281 the genetic background 260:281 the genetic background of cases with TAs 260:299 This study aims to explore the genetic background of cases with TAs in order to improve our knowledge of the pathogenesis of these rare pathological structures. 34908252 1 58 dep OBJECTIVE 66:74 arg1 reported 103:110 reported 103:110 have been reported to be associated with myopathies with tubular aggregates (TAs) 93:173 OBJECTIVE A group of genes have been reported to be associated with myopathies with tubular aggregates (TAs). 34908252 13 59 theme glycosylation 1583:1595 arg1 pathway 1597:1603 N-linked glycosylation pathway 1574:1603 N-linked glycosylation pathway 1574:1603 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 7 60 theme embryonic 753:761 arg1 kidney 763:768 human embryonic kidney 293 747:772 human embryonic kidney 293 cells (HEK293) 747:787 The wild-type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. 34908252 10 61 theme HEK293 1226:1231 arg1 cells 1233:1237 the mutant ALG14 HEK293 cells 1209:1237 the mutant ALG14 HEK293 cells (p.Ala11Thr) 1209:1250 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 10 61 theme HEK293 1226:1231 arg1 p.Ala11Thr 1240:1249 p.Ala11Thr 1240:1249 p.Ala11Thr 1240:1249 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 4 62 dep confirmed 465:473 arg1 biopsy 458:463 biopsy 458:463 biopsy 458:463 METHODS Thirty-three patients including two family members with biopsy confirmed TAs were collected. 34908252 13 63 theme calcium 1543:1549 arg1 pathway 1562:1568 calcium signalling pathway 1543:1568 calcium signalling pathway 1543:1568 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 34908252 2 64 theme Many 176:179 arg1 cases 181:185 Many cases 176:185 Many cases with TAs 176:194 Many cases with TAs still lack of genetic clarification. 34908252 5 65 theme unrelated 538:546 arg1 patients 554:561 31 unrelated index patients 535:561 31 unrelated index patients 535:561 Whole-exome sequencing was performed on 31 unrelated index patients and a candidate gene search strategy was conducted. 34908252 4 66 dep METHODS 394:400 arg1 patients 415:422 Thirty-three patients 402:422 METHODS Thirty-three patients including two family members with biopsy confirmed TAs 394:477 METHODS Thirty-three patients including two family members with biopsy confirmed TAs were collected. 34908252 4 66 dep METHODS 394:400 arg1 members 445:451 two family members 434:451 two family members with biopsy confirmed TAs 434:477 METHODS Thirty-three patients including two family members with biopsy confirmed TAs were collected. 34908252 10 67 theme ALG14 1220:1224 arg1 cells 1233:1237 the mutant ALG14 HEK293 cells 1209:1237 the mutant ALG14 HEK293 cells (p.Ala11Thr) 1209:1250 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 10 67 theme ALG14 1220:1224 arg1 p.Ala11Thr 1240:1249 p.Ala11Thr 1240:1249 p.Ala11Thr 1240:1249 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 2 68 theme clarification 218:230 arg1 lack 202:205 lack 202:205 lack of genetic clarification 202:230 Many cases with TAs still lack of genetic clarification. 34908252 10 69 theme blot 1127:1130 arg1 analysis 1132:1139 Western blot analysis 1119:1139 Western blot analysis 1119:1139 Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. 34908252 7 70 theme human 747:751 arg1 kidney 763:768 human embryonic kidney 293 747:772 human embryonic kidney 293 cells (HEK293) 747:787 The wild-type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. 34908252 2 71 theme genetic 210:216 arg1 clarification 218:230 genetic clarification 210:230 genetic clarification 210:230 Many cases with TAs still lack of genetic clarification. 34908252 5 72 theme Whole-exome 495:505 arg1 sequencing 507:516 Whole-exome sequencing 495:516 Whole-exome sequencing 495:516 Whole-exome sequencing was performed on 31 unrelated index patients and a candidate gene search strategy was conducted. 34908252 11 73 theme complex 1342:1348 arg1 disorders 1362:1370 complex multisystem disorders 1342:1370 complex multisystem disorders 1342:1370 The ALG14 variants might be associated with TAs in patients with complex multisystem disorders. 34908252 6 74 theme identified 619:628 arg1 variants 630:637 The identified variants 615:637 The identified variants 615:637 The identified variants were confirmed by Sanger sequencing. 34908252 0 75 theme tubular 46:52 arg1 aggregates 54:63 tubular aggregates 46:63 tubular aggregates 46:63 Genetic defects are common in myopathies with tubular aggregates. 34908252 0 76 from common 20:25 arg1 myopathies 30:39 myopathies 30:39 myopathies with tubular aggregates 30:63 Genetic defects are common in myopathies with tubular aggregates. 34908252 0 77 with myopathies 30:39 arg1 aggregates 54:63 tubular aggregates 46:63 tubular aggregates 46:63 Genetic defects are common in myopathies with tubular aggregates. 34908252 13 78 with myopathies 1636:1645 arg1 TAs 1652:1654 TAs 1652:1654 TAs 1652:1654 Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N-linked glycosylation pathway are the main genetic causes of myopathies with TAs. 33859256 5 0 theme activator 739:747 arg1 members 666:672 other members 660:672 other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), 660:754 We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. 33859256 6 1 gly glycoprotein 800:811 arg1 tPA 791:793 tPA 791:793 tPA 791:793 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 6 1 gly glycoprotein 800:811 arg1 glycoprotein 800:811 a glycoprotein 798:811 a glycoprotein with three N-linked glycosylation sites 798:851 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 0 2 theme receptor 83:90 arg1 activator 19:27 Tissue plasminogen activator 0:27 Tissue plasminogen activator 0:27 Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate. 33859256 0 2 theme receptor 83:90 arg1 ligand 34:39 a ligand 32:39 a ligand of cation-independent mannose 6-phosphate receptor 32:90 Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate. 33859256 4 3 theme CI-MPR 568:573 arg1 binding 575:581 CI-MPR binding 568:581 CI-MPR binding to plasminogen or urokinase plasminogen activator receptor 568:640 Plasminogen regulation may be accomplished by CI-MPR binding to plasminogen or urokinase plasminogen activator receptor. 33859256 10 4 theme tPA 1512:1514 arg1 position 1495:1502 position N448 1495:1507 position N448 of tPA 1495:1514 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 5 5 theme other 660:664 arg1 members 666:672 other members 660:672 other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), 660:754 We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. 33859256 1 6 theme key 168:170 arg1 enzyme 172:177 the key enzyme 164:177 the key enzyme in fibrinolysis 164:193 Plasmin is the key enzyme in fibrinolysis. 33859256 1 6 theme key 168:170 arg1 Plasmin 153:159 Plasmin 153:159 Plasmin 153:159 Plasmin is the key enzyme in fibrinolysis. 33859256 6 7 link N-linked 824:831 arg1 sites 847:851 three N-linked glycosylation sites 818:851 three N-linked glycosylation sites 818:851 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 6 8 theme glycosylation 833:845 arg1 sites 847:851 three N-linked glycosylation sites 818:851 three N-linked glycosylation sites 818:851 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 5 9 theme tissue 720:725 arg1 tPA 750:752 tPA 750:752 tPA 750:752 We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. 33859256 5 9 theme tissue 720:725 arg1 activator 739:747 tissue plasminogen activator 720:747 tissue plasminogen activator (tPA) 720:753 We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. 33859256 9 10 theme N-terminal 1226:1235 arg1 domains 1237:1243 the five N-terminal domains 1217:1243 the five N-terminal domains of CI-MPR 1217:1253 Subsequent studies revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interaction was also partially mediated by M6P. 33859256 9 10 theme N-terminal 1226:1235 arg1 sufficient 1260:1269 sufficient 1260:1269 sufficient 1260:1269 Subsequent studies revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interaction was also partially mediated by M6P. 33859256 9 10 theme N-terminal 1226:1235 arg1 CI-MPR 1248:1253 CI-MPR 1248:1253 CI-MPR 1248:1253 Subsequent studies revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interaction was also partially mediated by M6P. 33859256 7 11 theme surface 964:970 arg1 resonance 980:988 surface plasmon resonance 964:988 surface plasmon resonance 964:988 Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. 33859256 4 12 theme Plasminogen 522:532 arg1 regulation 534:543 Plasminogen regulation 522:543 Plasminogen regulation 522:543 Plasminogen regulation may be accomplished by CI-MPR binding to plasminogen or urokinase plasminogen activator receptor. 33859256 5 13 theme plasminogen 727:737 arg1 tPA 750:752 tPA 750:752 tPA 750:752 We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. 33859256 5 13 theme plasminogen 727:737 arg1 activator 739:747 tissue plasminogen activator 720:747 tissue plasminogen activator (tPA) 720:753 We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. 33859256 3 14 theme mannose 378:384 arg1 CI-MPR 408:413 CI-MPR 408:413 CI-MPR 408:413 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 3 14 theme mannose 378:384 arg1 receptor 398:405 cation-independent mannose 6-phosphate receptor 359:405 cation-independent mannose 6-phosphate receptor (CI-MPR) 359:414 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 3 14 theme mannose 378:384 arg1 protein 419:425 a protein 417:425 a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation 417:519 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 5 15 theme plasminogen 681:691 arg1 system 704:709 the plasminogen activation system 677:709 the plasminogen activation system 677:709 We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. 33859256 9 16 theme Subsequent 1184:1193 arg1 studies 1195:1201 Subsequent studies 1184:1201 Subsequent studies 1184:1201 Subsequent studies revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interaction was also partially mediated by M6P. 33859256 3 17 theme 6-phosphate 386:396 arg1 CI-MPR 408:413 CI-MPR 408:413 CI-MPR 408:413 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 3 17 theme 6-phosphate 386:396 arg1 receptor 398:405 cation-independent mannose 6-phosphate receptor 359:405 cation-independent mannose 6-phosphate receptor (CI-MPR) 359:414 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 3 17 theme 6-phosphate 386:396 arg1 protein 419:425 a protein 417:425 a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation 417:519 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 5 18 theme activation 693:702 arg1 system 704:709 the plasminogen activation system 677:709 the plasminogen activation system 677:709 We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. 33859256 9 19 theme CI-MPR 1248:1253 arg1 domains 1237:1243 the five N-terminal domains 1217:1243 the five N-terminal domains of CI-MPR 1217:1253 Subsequent studies revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interaction was also partially mediated by M6P. 33859256 9 19 theme CI-MPR 1248:1253 arg1 sufficient 1260:1269 sufficient 1260:1269 sufficient 1260:1269 Subsequent studies revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interaction was also partially mediated by M6P. 33859256 9 19 theme CI-MPR 1248:1253 arg1 CI-MPR 1248:1253 CI-MPR 1248:1253 CI-MPR 1248:1253 Subsequent studies revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interaction was also partially mediated by M6P. 33859256 2 20 theme active 282:287 arg1 plasmin 289:295 active plasmin 282:295 active plasmin 282:295 Upon interaction with plasminogen activators, the zymogen plasminogen is converted to active plasmin. 33859256 3 21 theme insulin-like 477:488 arg1 factor 497:502 insulin-like growth factor 2 477:504 insulin-like growth factor 2 downregulation 477:519 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 6 22 with glycoprotein 800:811 arg1 sites 847:851 three N-linked glycosylation sites 818:851 three N-linked glycosylation sites 818:851 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 5 23 theme system 704:709 arg1 members 666:672 other members 660:672 other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), 660:754 We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. 33859256 6 24 gly glycosylation 833:845 arg2 three 818:822 three 818:822 three 818:822 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 6 24 gly glycosylation 833:845 arg2 sites 847:851 three N-linked glycosylation sites 818:851 three N-linked glycosylation sites 818:851 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 3 25 theme enzyme 454:459 arg1 trafficking 461:471 lysosomal enzyme trafficking 444:471 lysosomal enzyme trafficking 444:471 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 0 26 theme Tissue 0:5 arg1 activator 19:27 Tissue plasminogen activator 0:27 Tissue plasminogen activator 0:27 Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate. 33859256 0 26 theme Tissue 0:5 arg1 ligand 34:39 a ligand 32:39 a ligand of cation-independent mannose 6-phosphate receptor 32:90 Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate. 33859256 4 27 theme plasminogen 611:621 arg1 activator 623:631 urokinase plasminogen activator 601:631 urokinase plasminogen activator 601:631 Plasminogen regulation may be accomplished by CI-MPR binding to plasminogen or urokinase plasminogen activator receptor. 33859256 6 28 theme N-linked 824:831 arg1 sites 847:851 three N-linked glycosylation sites 818:851 three N-linked glycosylation sites 818:851 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 10 29 theme glycosylation 1355:1367 arg1 tPA 1378:1380 tPA 1378:1380 tPA 1378:1380 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 10 29 theme glycosylation 1355:1367 arg1 sites 1369:1373 The three glycosylation sites 1345:1373 The three glycosylation sites of tPA 1345:1380 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 5 30 dep such 712:715 arg1 as 717:718 as 717:718 as 717:718 We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. 33859256 4 31 theme urokinase 601:609 arg1 activator 623:631 urokinase plasminogen activator 601:631 urokinase plasminogen activator 601:631 Plasminogen regulation may be accomplished by CI-MPR binding to plasminogen or urokinase plasminogen activator receptor. 33859256 0 32 theme mannose 132:138 arg1 6-phosphate 140:150 mannose 6-phosphate 132:150 mannose 6-phosphate 132:150 Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate. 33859256 7 33 theme plasmon 972:978 arg1 resonance 980:988 surface plasmon resonance 964:988 surface plasmon resonance 964:988 Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. 33859256 11 34 contain contains 1547:1554 arg2 M6P 1556:1558 M6P 1556:1558 M6P 1556:1558 In summary, we found that tPA contains M6P and is a CI-MPR ligand. 33859256 11 34 contain contains 1547:1554 arg1 tPA 1543:1545 tPA 1543:1545 tPA 1543:1545 In summary, we found that tPA contains M6P and is a CI-MPR ligand. 33859256 10 35 gly glycosylation 1355:1367 arg1 tPA 1378:1380 tPA 1378:1380 tPA 1378:1380 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 10 35 gly glycosylation 1355:1367 arg2 sites 1369:1373 The three glycosylation sites 1345:1373 The three glycosylation sites of tPA 1345:1380 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 10 35 gly glycosylation 1355:1367 arg2 three 1349:1353 three 1349:1353 three 1349:1353 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 10 35 gly glycosylation 1355:1367 arg2 tPA 1378:1380 tPA 1378:1380 tPA 1378:1380 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 9 36 theme tPA 1275:1277 arg1 binding 1279:1285 tPA binding 1275:1285 tPA binding 1275:1285 Subsequent studies revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interaction was also partially mediated by M6P. 33859256 0 37 contain contain 124:130 arg1 glycoforms 108:117 glycoforms 108:117 glycoforms that contain mannose 6-phosphate 108:150 Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate. 33859256 0 37 contain contain 124:130 arg2 6-phosphate 140:150 mannose 6-phosphate 132:150 mannose 6-phosphate 132:150 Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate. 33859256 4 38 theme activator 623:631 arg1 receptor 633:640 plasminogen or urokinase plasminogen activator receptor 586:640 plasminogen or urokinase plasminogen activator receptor 586:640 Plasminogen regulation may be accomplished by CI-MPR binding to plasminogen or urokinase plasminogen activator receptor. 33859256 2 39 theme zymogen 246:252 arg1 plasminogen 254:264 the zymogen plasminogen 242:264 the zymogen plasminogen 242:264 Upon interaction with plasminogen activators, the zymogen plasminogen is converted to active plasmin. 33859256 3 40 theme growth 490:495 arg1 factor 497:502 insulin-like growth factor 2 477:504 insulin-like growth factor 2 downregulation 477:519 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 3 41 theme lysosomal 444:452 arg1 trafficking 461:471 lysosomal enzyme trafficking 444:471 lysosomal enzyme trafficking 444:471 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 7 42 theme low-mid 1087:1093 arg1 affinities 1105:1114 low-mid nanomolar affinities 1087:1114 low-mid nanomolar affinities 1087:1114 Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. 33859256 3 43 theme factor 497:502 arg1 downregulation 506:519 insulin-like growth factor 2 downregulation 477:519 insulin-like growth factor 2 downregulation 477:519 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 0 44 theme cation-independent 44:61 arg1 receptor 83:90 cation-independent mannose 6-phosphate receptor 44:90 cation-independent mannose 6-phosphate receptor 44:90 Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate. 33859256 7 45 theme nanomolar 1095:1103 arg1 affinities 1105:1114 low-mid nanomolar affinities 1087:1114 low-mid nanomolar affinities 1087:1114 Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. 33859256 3 46 theme plasminogen 320:330 arg1 activation 332:341 plasminogen activation 320:341 plasminogen activation 320:341 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 0 47 theme mannose 63:69 arg1 receptor 83:90 cation-independent mannose 6-phosphate receptor 44:90 cation-independent mannose 6-phosphate receptor 44:90 Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate. 33859256 10 48 theme tPA 1378:1380 arg1 tPA 1378:1380 tPA 1378:1380 tPA 1378:1380 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 10 48 theme tPA 1378:1380 arg1 sites 1369:1373 The three glycosylation sites 1345:1373 The three glycosylation sites of tPA 1345:1380 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 6 49 theme M6P-dependent 936:948 arg1 manner 950:955 a M6P-dependent manner 934:955 a M6P-dependent manner 934:955 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 7 50 theme CI-MPR 1075:1080 arg1 region 1048:1053 the extracellular region 1030:1053 the extracellular region of human and bovine CI-MPR 1030:1080 Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. 33859256 2 51 theme plasminogen 218:228 arg1 activators 230:239 plasminogen activators 218:239 plasminogen activators 218:239 Upon interaction with plasminogen activators, the zymogen plasminogen is converted to active plasmin. 33859256 11 52 theme CI-MPR 1569:1574 arg1 ligand 1576:1581 a CI-MPR ligand 1567:1581 a CI-MPR ligand 1567:1581 In summary, we found that tPA contains M6P and is a CI-MPR ligand. 33859256 4 53 theme plasminogen 586:596 arg1 receptor 633:640 plasminogen or urokinase plasminogen activator receptor 586:640 plasminogen or urokinase plasminogen activator receptor 586:640 Plasminogen regulation may be accomplished by CI-MPR binding to plasminogen or urokinase plasminogen activator receptor. 33859256 7 54 theme human 1058:1062 arg1 CI-MPR 1075:1080 human and bovine CI-MPR 1058:1080 human and bovine CI-MPR 1058:1080 Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. 33859256 6 55 theme mannose 888:894 arg1 M6P 909:911 M6P 909:911 M6P 909:911 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 6 55 theme mannose 888:894 arg1 6-phosphate 896:906 mannose 6-phosphate 888:906 mannose 6-phosphate (M6P) 888:912 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 7 56 theme extracellular 1034:1046 arg1 region 1048:1053 the extracellular region 1030:1053 the extracellular region of human and bovine CI-MPR 1030:1080 Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. 33859256 8 57 theme phosphatase 1154:1164 arg1 treatment 1166:1174 phosphatase treatment 1154:1174 phosphatase treatment 1154:1174 Binding was partially inhibited with phosphatase treatment or M6P. 33859256 7 58 theme tPA 1020:1022 arg1 sources 1009:1015 two sources 1005:1015 two sources of tPA 1005:1022 Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. 33859256 0 59 theme 6-phosphate 71:81 arg1 receptor 83:90 cation-independent mannose 6-phosphate receptor 44:90 cation-independent mannose 6-phosphate receptor 44:90 Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate. 33859256 7 60 theme bovine 1068:1073 arg1 CI-MPR 1075:1080 human and bovine CI-MPR 1058:1080 human and bovine CI-MPR 1058:1080 Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. 33859256 10 61 theme mass 1399:1402 arg1 spectrometry 1404:1415 mass spectrometry 1399:1415 mass spectrometry 1399:1415 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 2 62 with interaction 201:211 arg1 activators 230:239 plasminogen activators 218:239 plasminogen activators 218:239 Upon interaction with plasminogen activators, the zymogen plasminogen is converted to active plasmin. 33859256 3 63 theme cation-independent 359:376 arg1 CI-MPR 408:413 CI-MPR 408:413 CI-MPR 408:413 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 3 63 theme cation-independent 359:376 arg1 receptor 398:405 cation-independent mannose 6-phosphate receptor 359:405 cation-independent mannose 6-phosphate receptor (CI-MPR) 359:414 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 3 63 theme cation-independent 359:376 arg1 protein 419:425 a protein 417:425 a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation 417:519 Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. 33859256 1 64 from enzyme 172:177 arg1 fibrinolysis 182:193 fibrinolysis 182:193 fibrinolysis 182:193 Plasmin is the key enzyme in fibrinolysis. 33859256 6 65 contain contains 879:886 arg1 tPA 875:877 tPA 875:877 tPA 875:877 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 6 65 contain contains 879:886 arg2 6-phosphate 896:906 mannose 6-phosphate 888:906 mannose 6-phosphate (M6P) 888:912 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 6 65 contain contains 879:886 arg2 M6P 909:911 M6P 909:911 M6P 909:911 Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. 33859256 10 66 contain containing 1433:1442 arg1 glycoforms 1422:1431 glycoforms 1422:1431 glycoforms containing M6P and M6P-N-acetylglucosamine 1422:1474 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 10 66 contain containing 1433:1442 arg2 M6P-N-acetylglucosamine 1452:1474 M6P-N-acetylglucosamine 1452:1474 M6P-N-acetylglucosamine 1452:1474 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33859256 10 66 contain containing 1433:1442 arg2 M6P 1444:1446 M6P 1444:1446 M6P 1444:1446 The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. 33439092 7 0 dep in 1108:1109 arg1 vivo 1111:1114 vivo 1111:1114 vivo 1111:1114 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 2 1 theme CfaE 355:358 arg1 antibody 374:381 a monoclonal anti-ETEC CfaE secretory IgA antibody 332:381 a monoclonal anti-ETEC CfaE secretory IgA antibody 332:381 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 6 2 theme in 944:945 arg1 model 953:957 an in vitro model 941:957 an in vitro model 941:957 Susceptibility to gastric digestion was assessed in an in vitro model. 33439092 10 3 theme activity 1435:1442 arg1 alteration 1401:1410 no alteration 1398:1410 no alteration of in vitro functional activity 1398:1442 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 12 4 theme passive 1848:1854 arg1 immunotherapy 1856:1868 passive immunotherapy 1848:1868 passive immunotherapy in LMICs 1848:1877 Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs. 33439092 9 5 theme simulated 1242:1250 arg1 fluid 1260:1264 simulated gastric fluid 1242:1264 simulated gastric fluid 1242:1264 Both sub-classes exhibited resistance to degradation by simulated gastric fluid, comparable to CHO-produced 68-61 SIgA1. 33439092 1 6 theme promising 171:179 arg1 approach 181:188 a promising approach 169:188 a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs 169:268 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 1 6 theme promising 171:179 arg1 immunization 137:148 Passive immunization 129:148 Passive immunization with antibodies 129:164 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 7 7 theme challenge 1116:1124 arg1 study 1126:1130 a murine in vivo challenge study 1099:1130 a murine in vivo challenge study 1099:1130 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 7 theme challenge 1116:1124 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 11 8 theme murine 1626:1631 arg1 model 1643:1647 a murine infection model 1624:1647 a murine infection model 1624:1647 The plant-derived SIgA2 mAb demonstrated protection against diarrhea in a murine infection model. 33439092 3 9 theme heavy 566:570 arg1 chains 572:577 engineered heavy chains 555:577 engineered heavy chains with J chain and secretory component in N. benthamiana 555:632 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 7 10 theme in 1108:1109 arg1 study 1126:1130 a murine in vivo challenge study 1099:1130 a murine in vivo challenge study 1099:1130 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 10 theme in 1108:1109 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 3 11 theme mAb 500:502 arg1 forms 491:495 SIgA1 and SIgA2 forms 475:495 SIgA1 and SIgA2 forms of mAb 68-81 475:508 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 1 12 theme Escherichia 214:224 arg1 disease 253:259 a prevalent disease 241:259 a prevalent disease in LMICs 241:268 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 1 12 theme Escherichia 214:224 arg1 diarrhea 231:238 enterotoxigenic Escherichia coli diarrhea 198:238 enterotoxigenic Escherichia coli diarrhea 198:238 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 4 13 theme Antibody 635:642 arg1 expression 644:653 Antibody expression 635:653 Antibody expression 635:653 Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. 33439092 9 14 theme CHO-produced 1281:1292 arg1 SIgA1 1300:1304 CHO-produced 68-61 SIgA1 1281:1304 CHO-produced 68-61 SIgA1 1281:1304 Both sub-classes exhibited resistance to degradation by simulated gastric fluid, comparable to CHO-produced 68-61 SIgA1. 33439092 5 15 theme rapid 837:841 arg1 spectrometry 861:872 rapid fluorescence/mass spectrometry 837:872 rapid fluorescence/mass spectrometry 837:872 N-linked glycosylation was assessed by rapid fluorescence/mass spectrometry and LC-ESI-MS. 33439092 1 16 from disease 253:259 arg1 LMICs 264:268 LMICs 264:268 LMICs 264:268 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 5 17 link N-linked 798:805 arg1 glycosylation 807:819 N-linked glycosylation 798:819 N-linked glycosylation 798:819 N-linked glycosylation was assessed by rapid fluorescence/mass spectrometry and LC-ESI-MS. 33439092 7 18 theme adhesion 1037:1044 arg1 assay 1046:1050 a Caco-2 cell-based ETEC adhesion assay 1012:1050 a Caco-2 cell-based ETEC adhesion assay 1012:1050 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 18 theme adhesion 1037:1044 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 4 19 theme western 723:729 arg1 blotting 731:738 western blotting 723:738 western blotting 723:738 Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. 33439092 11 20 theme plant-derived 1556:1568 arg1 mAb 1576:1578 The plant-derived SIgA2 mAb 1552:1578 The plant-derived SIgA2 mAb 1552:1578 The plant-derived SIgA2 mAb demonstrated protection against diarrhea in a murine infection model. 33439092 7 21 theme hemagglutination 1061:1076 arg1 assay 1089:1093 an ETEC hemagglutination inhibition assay 1053:1093 an ETEC hemagglutination inhibition assay 1053:1093 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 21 theme hemagglutination 1061:1076 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 22 theme cell-based 1021:1030 arg1 assay 1046:1050 a Caco-2 cell-based ETEC adhesion assay 1012:1050 a Caco-2 cell-based ETEC adhesion assay 1012:1050 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 22 theme cell-based 1021:1030 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 1 23 theme Passive 129:135 arg1 approach 181:188 a promising approach 169:188 a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs 169:268 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 1 23 theme Passive 129:135 arg1 immunization 137:148 Passive immunization 129:148 Passive immunization with antibodies 129:164 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 12 24 theme CHO 1808:1810 arg1 antibodies 1812:1821 CHO antibodies 1808:1821 CHO antibodies 1808:1821 Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs. 33439092 3 25 theme secretory 596:604 arg1 component 606:614 secretory component 596:614 secretory component in N. benthamiana 596:632 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 12 26 theme plant 1762:1766 arg1 platform 1768:1775 a low-cost plant platform 1751:1775 a low-cost plant platform 1751:1775 Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs. 33439092 10 27 contain had 1333:1335 arg2 N-glycosylation 1354:1368 more homogeneous N-glycosylation 1337:1368 more homogeneous N-glycosylation 1337:1368 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 10 27 contain had 1333:1335 arg1 SIgAs 1327:1331 The plant expressed SIgAs 1307:1331 The plant expressed SIgAs 1307:1331 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 2 28 from expression 318:327 arg1 plants 401:406 N. benthamiana plants 386:406 N. benthamiana plants 386:406 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 4 29 theme LC-MS 775:779 arg1 mapping 789:795 LC-MS peptide mapping 775:795 LC-MS peptide mapping 775:795 Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. 33439092 0 30 theme secretory 94:102 arg1 IgA1 104:107 IgA1 104:107 IgA1 104:107 Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants. 33439092 10 31 theme N 1535:1535 arg1 glycosylation 1537:1549 mammalian-like N glycosylation 1520:1549 mammalian-like N glycosylation 1520:1549 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 10 32 theme expressed 1317:1325 arg1 SIgAs 1327:1331 The plant expressed SIgAs 1307:1331 The plant expressed SIgAs 1307:1331 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 2 33 theme N. 386:387 arg1 plants 401:406 N. benthamiana plants 386:406 N. benthamiana plants 386:406 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 7 34 theme Antibody 960:967 arg1 function 969:976 Antibody function 960:976 Antibody function 960:976 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 5 35 theme fluorescence/mass 843:859 arg1 spectrometry 861:872 rapid fluorescence/mass spectrometry 837:872 rapid fluorescence/mass spectrometry 837:872 N-linked glycosylation was assessed by rapid fluorescence/mass spectrometry and LC-ESI-MS. 33439092 3 36 from chain 586:590 arg1 benthamiana 622:632 N. benthamiana 619:632 N. benthamiana 619:632 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 12 37 theme SIgA 1723:1726 arg1 antibodies 1728:1737 anti-ETEC SIgA antibodies 1713:1737 anti-ETEC SIgA antibodies produced in a low-cost plant platform 1713:1775 Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs. 33439092 10 38 theme homogeneous 1342:1352 arg1 N-glycosylation 1354:1368 more homogeneous N-glycosylation 1337:1368 more homogeneous N-glycosylation 1337:1368 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 0 39 theme antibody 30:37 arg1 Investigation 0:12 Investigation 0:12 Investigation 0:12 Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants. 33439092 5 40 theme N-linked 798:805 arg1 glycosylation 807:819 N-linked glycosylation 798:819 N-linked glycosylation 798:819 N-linked glycosylation was assessed by rapid fluorescence/mass spectrometry and LC-ESI-MS. 33439092 8 41 from SIgA2 1169:1173 arg1 plants 1178:1183 plants 1178:1183 plants 1178:1183 SIgA1 assembly appeared superior to SIgA2 in plants. 33439092 2 42 theme passive 452:458 arg1 immunotherapy 460:472 ETEC passive immunotherapy 447:472 ETEC passive immunotherapy 447:472 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 3 43 theme SIgA2 485:489 arg1 forms 491:495 SIgA1 and SIgA2 forms 475:495 SIgA1 and SIgA2 forms of mAb 68-81 475:508 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 8 44 theme SIgA1 1133:1137 arg1 assembly 1139:1146 SIgA1 assembly 1133:1146 SIgA1 assembly 1133:1146 SIgA1 assembly appeared superior to SIgA2 in plants. 33439092 10 45 link CHO-derived 1375:1385 arg1 SIgAs 1387:1391 CHO-derived SIgAs 1375:1391 CHO-derived SIgAs 1375:1391 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 3 46 theme SIgA1 475:479 arg1 forms 491:495 SIgA1 and SIgA2 forms 475:495 SIgA1 and SIgA2 forms of mAb 68-81 475:508 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 10 47 theme in 1415:1416 arg1 activity 1435:1442 in vitro functional activity 1415:1442 in vitro functional activity 1415:1442 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 2 48 theme antibody 374:381 arg1 expression 318:327 expression 318:327 expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants 318:406 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 1 49 theme prevalent 243:251 arg1 disease 253:259 a prevalent disease 241:259 a prevalent disease in LMICs 241:268 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 1 49 theme prevalent 243:251 arg1 diarrhea 231:238 enterotoxigenic Escherichia coli diarrhea 198:238 enterotoxigenic Escherichia coli diarrhea 198:238 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 2 50 theme secretory 360:368 arg1 antibody 374:381 a monoclonal anti-ETEC CfaE secretory IgA antibody 332:381 a monoclonal anti-ETEC CfaE secretory IgA antibody 332:381 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 6 51 dep in 944:945 arg1 vitro 947:951 vitro 947:951 vitro 947:951 Susceptibility to gastric digestion was assessed in an in vitro model. 33439092 2 52 theme study 293:297 arg1 objective 275:283 The objective 271:283 The objective of this study 271:297 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 2 53 theme anti-ETEC 345:353 arg1 antibody 374:381 a monoclonal anti-ETEC CfaE secretory IgA antibody 332:381 a monoclonal anti-ETEC CfaE secretory IgA antibody 332:381 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 10 54 theme functional 1424:1433 arg1 activity 1435:1442 in vitro functional activity 1415:1442 in vitro functional activity 1415:1442 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 9 55 theme gastric 1252:1258 arg1 fluid 1260:1264 simulated gastric fluid 1242:1264 simulated gastric fluid 1242:1264 Both sub-classes exhibited resistance to degradation by simulated gastric fluid, comparable to CHO-produced 68-61 SIgA1. 33439092 3 56 theme engineered 555:564 arg1 chains 572:577 engineered heavy chains 555:577 engineered heavy chains with J chain and secretory component in N. benthamiana 555:632 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 10 57 dep in 1415:1416 arg1 vitro 1418:1422 vitro 1418:1422 vitro 1418:1422 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 4 58 link CHO-derived 687:697 arg1 antibodies 699:708 CHO-derived antibodies 687:708 CHO-derived antibodies 687:708 Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. 33439092 7 59 theme murine 1101:1106 arg1 study 1126:1130 a murine in vivo challenge study 1099:1130 a murine in vivo challenge study 1099:1130 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 59 theme murine 1101:1106 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 11 60 theme infection 1633:1641 arg1 model 1643:1647 a murine infection model 1624:1647 a murine infection model 1624:1647 The plant-derived SIgA2 mAb demonstrated protection against diarrhea in a murine infection model. 33439092 1 61 theme enterotoxigenic 198:212 arg1 disease 253:259 a prevalent disease 241:259 a prevalent disease in LMICs 241:268 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 1 61 theme enterotoxigenic 198:212 arg1 diarrhea 231:238 enterotoxigenic Escherichia coli diarrhea 198:238 enterotoxigenic Escherichia coli diarrhea 198:238 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 3 62 theme J 584:584 arg1 chain 586:590 J chain 584:590 J chain 584:590 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 12 63 theme antibody 1659:1666 arg1 yield 1668:1672 antibody yield 1659:1672 antibody yield 1659:1672 Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs. 33439092 7 64 theme inhibition 1078:1087 arg1 assay 1089:1093 an ETEC hemagglutination inhibition assay 1053:1093 an ETEC hemagglutination inhibition assay 1053:1093 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 64 theme inhibition 1078:1087 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 9 65 theme 68-61 1294:1298 arg1 SIgA1 1300:1304 CHO-produced 68-61 SIgA1 1281:1304 CHO-produced 68-61 SIgA1 1281:1304 Both sub-classes exhibited resistance to degradation by simulated gastric fluid, comparable to CHO-produced 68-61 SIgA1. 33439092 0 66 from IgA2 113:116 arg1 plants 121:126 plants 121:126 plants 121:126 Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants. 33439092 7 67 theme ETEC 1056:1059 arg1 assay 1089:1093 an ETEC hemagglutination inhibition assay 1053:1093 an ETEC hemagglutination inhibition assay 1053:1093 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 67 theme ETEC 1056:1059 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 0 68 from IgA1 104:107 arg1 plants 121:126 plants 121:126 plants 121:126 Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants. 33439092 11 69 link plant-derived 1556:1568 arg1 mAb 1576:1578 The plant-derived SIgA2 mAb 1552:1578 The plant-derived SIgA2 mAb 1552:1578 The plant-derived SIgA2 mAb demonstrated protection against diarrhea in a murine infection model. 33439092 10 70 dep expressed 1317:1325 arg1 plant 1311:1315 plant 1311:1315 plant 1311:1315 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 7 71 theme Caco-2 1014:1019 arg1 assay 1046:1050 a Caco-2 cell-based ETEC adhesion assay 1012:1050 a Caco-2 cell-based ETEC adhesion assay 1012:1050 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 71 theme Caco-2 1014:1019 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 12 72 theme low-cost 1753:1760 arg1 platform 1768:1775 a low-cost plant platform 1751:1775 a low-cost plant platform 1751:1775 Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs. 33439092 10 73 theme plant 1494:1498 arg1 line 1500:1503 a plant line 1492:1503 a plant line engineered for mammalian-like N glycosylation 1492:1549 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 4 74 theme CHO-derived 687:697 arg1 antibodies 699:708 CHO-derived antibodies 687:708 CHO-derived antibodies 687:708 Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. 33439092 11 75 theme SIgA2 1570:1574 arg1 mAb 1576:1578 The plant-derived SIgA2 mAb 1552:1578 The plant-derived SIgA2 mAb 1552:1578 The plant-derived SIgA2 mAb demonstrated protection against diarrhea in a murine infection model. 33439092 3 76 with chains 572:577 arg1 chain 586:590 J chain 584:590 J chain 584:590 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 3 76 with chains 572:577 arg1 component 606:614 secretory component 596:614 secretory component in N. benthamiana 596:632 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 1 77 with immunization 137:148 arg1 antibodies 155:164 antibodies 155:164 antibodies 155:164 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 7 78 theme antigen 995:1001 arg1 study 1126:1130 a murine in vivo challenge study 1099:1130 a murine in vivo challenge study 1099:1130 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 78 theme antigen 995:1001 arg1 assay 1046:1050 a Caco-2 cell-based ETEC adhesion assay 1012:1050 a Caco-2 cell-based ETEC adhesion assay 1012:1050 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 78 theme antigen 995:1001 arg1 assay 1089:1093 an ETEC hemagglutination inhibition assay 1053:1093 an ETEC hemagglutination inhibition assay 1053:1093 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 78 theme antigen 995:1001 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 12 79 from immunotherapy 1856:1868 arg1 LMICs 1873:1877 LMICs 1873:1877 LMICs 1873:1877 Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs. 33439092 10 80 theme mammalian-like 1520:1533 arg1 glycosylation 1537:1549 mammalian-like N glycosylation 1520:1549 mammalian-like N glycosylation 1520:1549 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 4 81 theme peptide 781:787 arg1 mapping 789:795 LC-MS peptide mapping 775:795 LC-MS peptide mapping 775:795 Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. 33439092 3 82 from component 606:614 arg1 benthamiana 622:632 N. benthamiana 619:632 N. benthamiana 619:632 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 2 83 theme benthamiana 389:399 arg1 plants 401:406 N. benthamiana plants 386:406 N. benthamiana plants 386:406 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 3 84 with light 545:549 arg1 chain 586:590 J chain 584:590 J chain 584:590 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 3 84 with light 545:549 arg1 component 606:614 secretory component 596:614 secretory component in N. benthamiana 596:632 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 10 85 theme CHO-derived 1375:1385 arg1 SIgAs 1387:1391 CHO-derived SIgAs 1375:1391 CHO-derived SIgAs 1375:1391 The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. 33439092 0 86 theme monoclonal 19:28 arg1 antibody 30:37 a monoclonal antibody 17:37 a monoclonal antibody against enterotoxigenic Escherichia coli 17:78 Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants. 33439092 4 87 theme size-exclusion 741:754 arg1 chromatography 756:769 size-exclusion chromatography 741:769 size-exclusion chromatography 741:769 Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. 33439092 6 88 theme gastric 907:913 arg1 digestion 915:923 gastric digestion 907:923 gastric digestion 907:923 Susceptibility to gastric digestion was assessed in an in vitro model. 33439092 12 89 theme anti-ETEC 1713:1721 arg1 antibodies 1728:1737 anti-ETEC SIgA antibodies 1713:1737 anti-ETEC SIgA antibodies produced in a low-cost plant platform 1713:1775 Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs. 33439092 3 90 theme N. 619:620 arg1 benthamiana 622:632 N. benthamiana 619:632 N. benthamiana 619:632 SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. 33439092 2 91 theme ETEC 447:450 arg1 immunotherapy 460:472 ETEC passive immunotherapy 447:472 ETEC passive immunotherapy 447:472 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 2 92 theme monoclonal 334:343 arg1 antibody 374:381 a monoclonal anti-ETEC CfaE secretory IgA antibody 332:381 a monoclonal anti-ETEC CfaE secretory IgA antibody 332:381 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 33439092 7 93 theme ETEC 1032:1035 arg1 assay 1046:1050 a Caco-2 cell-based ETEC adhesion assay 1012:1050 a Caco-2 cell-based ETEC adhesion assay 1012:1050 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 7 93 theme ETEC 1032:1035 arg1 binding 1003:1009 antigen binding 995:1009 antigen binding 995:1009 Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. 33439092 1 94 dep Escherichia 214:224 arg1 coli 226:229 coli 226:229 coli 226:229 Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. 33439092 2 95 theme IgA 370:372 arg1 antibody 374:381 a monoclonal anti-ETEC CfaE secretory IgA antibody 332:381 a monoclonal anti-ETEC CfaE secretory IgA antibody 332:381 The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. 35162960 6 0 theme enzyme 1041:1046 arg1 methods 1056:1062 enzyme kinetic methods 1041:1062 enzyme kinetic methods against hOGA and hHexB 1041:1085 Evaluation of these compounds by enzyme kinetic methods against hOGA and hHexB revealed potent nanomolar competitive inhibition of both enzymes, with no significant selectivity towards either. 35162960 1 1 theme hOGA 192:195 arg1 enzyme 204:209 the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme 146:209 enzyme 204:209 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 9 2 theme sulfonylhydrazones 1599:1616 arg1 preference 1561:1570 the binding preference 1549:1570 the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds 1549:1664 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 0 3 theme OGA 110:112 arg1 Enzymes 123:129 Human OGA and HexB Enzymes 104:129 Human OGA and HexB Enzymes 104:129 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 35162960 9 4 theme Prime 1460:1464 arg1 refinement 1481:1490 Prime protein-ligand refinement and QM/MM optimizations 1460:1514 refinement 1481:1490 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 9 5 theme inhibitors 1417:1426 arg1 mode 1403:1406 the binding mode 1391:1406 the binding mode of these inhibitors to hOGA 1391:1434 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 1 6 theme cardiovascular 291:304 arg1 disorders 306:314 neurodegenerative and cardiovascular disorders 269:314 disorders 306:314 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 0 7 theme Enzymes 123:129 arg1 Inhibitors 90:99 Inhibitors 90:99 Inhibitors of Human OGA and HexB Enzymes 90:129 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 35162960 9 8 theme protein-ligand 1466:1479 arg1 refinement 1481:1490 Prime protein-ligand refinement and QM/MM optimizations 1460:1514 refinement 1481:1490 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 6 9 theme potent 1096:1101 arg1 inhibition 1125:1134 potent nanomolar competitive inhibition 1096:1134 potent nanomolar competitive inhibition of both enzymes 1096:1150 Evaluation of these compounds by enzyme kinetic methods against hOGA and hHexB revealed potent nanomolar competitive inhibition of both enzymes, with no significant selectivity towards either. 35162960 6 10 theme compounds 1028:1036 arg1 Evaluation 1008:1017 Evaluation 1008:1017 Evaluation of these compounds by enzyme kinetic methods against hOGA and hHexB 1008:1085 Evaluation of these compounds by enzyme kinetic methods against hOGA and hHexB revealed potent nanomolar competitive inhibition of both enzymes, with no significant selectivity towards either. 35162960 3 11 theme structure-activity 558:575 arg1 relationships 577:589 the structure-activity relationships 554:589 the structure-activity relationships of OGA inhibitors 554:607 In order to extend the structure-activity relationships of OGA inhibitors, a series of 2-acetamido-2-deoxy-d-glucono-1,5-lactone sulfonylhydrazones was prepared from d-glucosamine. 35162960 4 12 theme corresponding 870:882 arg1 sulfonylhydrazones 904:921 the corresponding glucono-1,5-lactone sulfonylhydrazones 866:921 the corresponding glucono-1,5-lactone sulfonylhydrazones 866:921 The synthetic sequence involved condensation of N-acetyl-3,4,6-tri-O-acetyl-d-glucosamine with arenesulfonylhydrazines, followed by MnO2 oxidation to the corresponding glucono-1,5-lactone sulfonylhydrazones. 35162960 0 13 theme HexB 118:121 arg1 Enzymes 123:129 Human OGA and HexB Enzymes 104:129 Human OGA and HexB Enzymes 104:129 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 35162960 1 14 from cancer 338:343 arg1 relevant 232:239 relevant 232:239 relevant 232:239 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 2 15 theme lysosomal 352:360 arg1 hHexB 389:393 hHexB 389:393 hHexB 389:393 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 15 theme lysosomal 352:360 arg1 hHexA 379:383 hHexA 379:383 hHexA 379:383 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 15 theme lysosomal 352:360 arg1 hexosaminidases 362:376 Human lysosomal hexosaminidases 346:376 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) 346:400 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 15 theme lysosomal 352:360 arg1 enzymes 430:436 mechanistically related enzymes 406:436 mechanistically related enzymes 406:436 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 15 theme lysosomal 352:360 arg1 GH20 396:399 GH20 396:399 GH20 396:399 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 1 16 from diabetes 324:331 arg1 relevant 232:239 relevant 232:239 relevant 232:239 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 9 17 theme s-cis 1624:1628 arg1 conformation 1630:1641 an s-cis conformation 1621:1641 an s-cis conformation 1621:1641 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 2 18 theme related 422:428 arg1 hexosaminidases 362:376 Human lysosomal hexosaminidases 346:376 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) 346:400 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 18 theme related 422:428 arg1 enzymes 430:436 mechanistically related enzymes 406:436 mechanistically related enzymes 406:436 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 5 19 theme groups 959:964 arg1 Removal 924:930 Removal 924:930 Removal of the O-acetyl protecting groups by NH3/MeOH 924:976 Removal of the O-acetyl protecting groups by NH3/MeOH furnished the test compounds. 35162960 6 20 theme kinetic 1048:1054 arg1 methods 1056:1062 enzyme kinetic methods 1041:1062 enzyme kinetic methods against hOGA and hHexB 1041:1085 Evaluation of these compounds by enzyme kinetic methods against hOGA and hHexB revealed potent nanomolar competitive inhibition of both enzymes, with no significant selectivity towards either. 35162960 7 21 theme Ki 1320:1321 arg1 nM 1328:1329 Ki = 27 nM 1320:1329 Ki = 27 nM 1320:1329 The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). 35162960 8 22 theme nM 1363:1364 arg1 Ki 1353:1354 a Ki 1351:1354 a Ki of 6.8 nM towards hHexB 1351:1378 This compound had a Ki of 6.8 nM towards hHexB. 35162960 2 23 from crucial 491:497 arg1 terms 502:506 terms 502:506 terms of potential applications 502:532 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 0 24 theme Human 104:108 arg1 Enzymes 123:129 Human OGA and HexB Enzymes 104:129 Human OGA and HexB Enzymes 104:129 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 35162960 2 25 theme Human 346:350 arg1 hHexB 389:393 hHexB 389:393 hHexB 389:393 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 25 theme Human 346:350 arg1 hHexA 379:383 hHexA 379:383 hHexA 379:383 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 25 theme Human 346:350 arg1 hexosaminidases 362:376 Human lysosomal hexosaminidases 346:376 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) 346:400 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 25 theme Human 346:350 arg1 enzymes 430:436 mechanistically related enzymes 406:436 mechanistically related enzymes 406:436 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 25 theme Human 346:350 arg1 GH20 396:399 GH20 396:399 GH20 396:399 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 26 dep hexosaminidases 362:376 arg1 hHexB 389:393 hHexB 389:393 hHexB 389:393 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 26 dep hexosaminidases 362:376 arg1 hHexA 379:383 hHexA 379:383 hHexA 379:383 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 26 dep hexosaminidases 362:376 arg1 hexosaminidases 362:376 Human lysosomal hexosaminidases 346:376 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) 346:400 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 2 26 dep hexosaminidases 362:376 arg1 GH20 396:399 GH20 396:399 GH20 396:399 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 1 27 theme enzyme 204:209 arg1 Inhibition 132:141 Inhibition 132:141 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme 132:209 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 0 28 theme 2-Acetamido-2-deoxy-d-glucono-1,5-lactone 0:40 arg1 Evaluation 76:85 Evaluation 76:85 Evaluation 76:85 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 35162960 0 28 theme 2-Acetamido-2-deoxy-d-glucono-1,5-lactone 0:40 arg1 Synthesis 62:70 Synthesis 62:70 Synthesis 62:70 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 35162960 0 28 theme 2-Acetamido-2-deoxy-d-glucono-1,5-lactone 0:40 arg1 Sulfonylhydrazones 42:59 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones 0:59 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 0:130 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 35162960 1 29 theme type 317:320 arg1 diabetes 324:331 type 2 diabetes 317:331 type 2 diabetes 317:331 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 1 29 theme type 317:320 arg1 disorders 306:314 neurodegenerative and cardiovascular disorders 269:314 disorders 306:314 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 4 30 theme MnO2 848:851 arg1 oxidation 853:861 MnO2 oxidation 848:861 MnO2 oxidation to the corresponding glucono-1,5-lactone sulfonylhydrazones 848:921 The synthetic sequence involved condensation of N-acetyl-3,4,6-tri-O-acetyl-d-glucosamine with arenesulfonylhydrazines, followed by MnO2 oxidation to the corresponding glucono-1,5-lactone sulfonylhydrazones. 35162960 8 31 contain had 1347:1349 arg1 compound 1338:1345 This compound 1333:1345 This compound 1333:1345 This compound had a Ki of 6.8 nM towards hHexB. 35162960 8 31 contain had 1347:1349 arg2 Ki 1353:1354 a Ki 1351:1354 a Ki of 6.8 nM towards hHexB 1351:1378 This compound had a Ki of 6.8 nM towards hHexB. 35162960 4 32 with condensation 748:759 arg1 arenesulfonylhydrazines 811:833 arenesulfonylhydrazines 811:833 arenesulfonylhydrazines 811:833 The synthetic sequence involved condensation of N-acetyl-3,4,6-tri-O-acetyl-d-glucosamine with arenesulfonylhydrazines, followed by MnO2 oxidation to the corresponding glucono-1,5-lactone sulfonylhydrazones. 35162960 3 33 theme sulfonylhydrazones 664:681 arg1 series 612:617 a series 610:617 a series of 2-acetamido-2-deoxy-d-glucono-1,5-lactone sulfonylhydrazones 610:681 In order to extend the structure-activity relationships of OGA inhibitors, a series of 2-acetamido-2-deoxy-d-glucono-1,5-lactone sulfonylhydrazones was prepared from d-glucosamine. 35162960 7 34 theme 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1242:1282 arg1 inhibitor 1220:1228 The most efficient inhibitor 1201:1228 The most efficient inhibitor of hOGA 1201:1236 The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). 35162960 7 34 theme 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1242:1282 arg1 5f 1316:1317 5f 1316:1317 5f 1316:1317 The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). 35162960 7 34 theme 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1242:1282 arg1 1-naphthalenesulfonylhydrazone 1284:1313 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone 1242:1313 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM) 1242:1330 The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). 35162960 9 35 theme binding 1395:1401 arg1 mode 1403:1406 the binding mode 1391:1406 the binding mode of these inhibitors to hOGA 1391:1434 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 4 36 theme glucono-1,5-lactone 884:902 arg1 sulfonylhydrazones 904:921 the corresponding glucono-1,5-lactone sulfonylhydrazones 866:921 the corresponding glucono-1,5-lactone sulfonylhydrazones 866:921 The synthetic sequence involved condensation of N-acetyl-3,4,6-tri-O-acetyl-d-glucosamine with arenesulfonylhydrazines, followed by MnO2 oxidation to the corresponding glucono-1,5-lactone sulfonylhydrazones. 35162960 9 37 theme binding 1553:1559 arg1 preference 1561:1570 the binding preference 1549:1570 the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds 1549:1664 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 5 38 theme test 992:995 arg1 compounds 997:1005 the test compounds 988:1005 the test compounds 988:1005 Removal of the O-acetyl protecting groups by NH3/MeOH furnished the test compounds. 35162960 2 39 theme selective 450:458 arg1 inhibition 460:469 selective inhibition 450:469 selective inhibition of these enzymes 450:486 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 9 40 dep studies 1451:1457 arg1 refinement 1481:1490 Prime protein-ligand refinement and QM/MM optimizations 1460:1514 refinement 1481:1490 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 9 40 dep studies 1451:1457 arg1 optimizations 1502:1514 Prime protein-ligand refinement and QM/MM optimizations 1460:1514 optimizations 1502:1514 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 3 41 theme OGA 594:596 arg1 inhibitors 598:607 OGA inhibitors 594:607 OGA inhibitors 594:607 In order to extend the structure-activity relationships of OGA inhibitors, a series of 2-acetamido-2-deoxy-d-glucono-1,5-lactone sulfonylhydrazones was prepared from d-glucosamine. 35162960 9 42 from sulfonylhydrazones 1599:1616 arg1 conformation 1630:1641 an s-cis conformation 1621:1641 an s-cis conformation 1621:1641 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 9 43 from preference 1561:1570 arg1 conformation 1630:1641 an s-cis conformation 1621:1641 an s-cis conformation 1621:1641 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 7 44 theme hOGA 1233:1236 arg1 inhibitor 1220:1228 The most efficient inhibitor 1201:1228 The most efficient inhibitor of hOGA 1201:1236 The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). 35162960 7 44 theme hOGA 1233:1236 arg1 1-naphthalenesulfonylhydrazone 1284:1313 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone 1242:1313 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM) 1242:1330 The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). 35162960 2 45 from terms 502:506 arg1 crucial 491:497 crucial 491:497 crucial 491:497 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 1 46 dep enzyme 204:209 arg1 GH84 198:201 the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme 146:209 GH84 198:201 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 9 47 theme test 1651:1654 arg1 compounds 1656:1664 all test compounds 1647:1664 all test compounds 1647:1664 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 4 48 theme synthetic 720:728 arg1 sequence 730:737 The synthetic sequence 716:737 The synthetic sequence 716:737 The synthetic sequence involved condensation of N-acetyl-3,4,6-tri-O-acetyl-d-glucosamine with arenesulfonylhydrazines, followed by MnO2 oxidation to the corresponding glucono-1,5-lactone sulfonylhydrazones. 35162960 5 49 theme O-acetyl 939:946 arg1 groups 959:964 the O-acetyl protecting groups 935:964 the O-acetyl protecting groups 935:964 Removal of the O-acetyl protecting groups by NH3/MeOH furnished the test compounds. 35162960 6 50 theme significant 1161:1171 arg1 selectivity 1173:1183 no significant selectivity 1158:1183 no significant selectivity towards either 1158:1198 Evaluation of these compounds by enzyme kinetic methods against hOGA and hHexB revealed potent nanomolar competitive inhibition of both enzymes, with no significant selectivity towards either. 35162960 3 51 theme 2-acetamido-2-deoxy-d-glucono-1,5-lactone 622:662 arg1 sulfonylhydrazones 664:681 2-acetamido-2-deoxy-d-glucono-1,5-lactone sulfonylhydrazones 622:681 2-acetamido-2-deoxy-d-glucono-1,5-lactone sulfonylhydrazones 622:681 In order to extend the structure-activity relationships of OGA inhibitors, a series of 2-acetamido-2-deoxy-d-glucono-1,5-lactone sulfonylhydrazones was prepared from d-glucosamine. 35162960 1 52 theme several 244:250 arg1 diseases 252:259 several diseases 244:259 several diseases such as neurodegenerative and cardiovascular disorders 244:314 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 1 52 theme several 244:250 arg1 disorders 306:314 neurodegenerative and cardiovascular disorders 269:314 disorders 306:314 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 5 53 theme protecting 948:957 arg1 groups 959:964 the O-acetyl protecting groups 935:964 the O-acetyl protecting groups 935:964 Removal of the O-acetyl protecting groups by NH3/MeOH furnished the test compounds. 35162960 6 54 theme competitive 1113:1123 arg1 inhibition 1125:1134 potent nanomolar competitive inhibition 1096:1134 potent nanomolar competitive inhibition of both enzymes 1096:1150 Evaluation of these compounds by enzyme kinetic methods against hOGA and hHexB revealed potent nanomolar competitive inhibition of both enzymes, with no significant selectivity towards either. 35162960 6 55 theme enzymes 1144:1150 arg1 inhibition 1125:1134 potent nanomolar competitive inhibition 1096:1134 potent nanomolar competitive inhibition of both enzymes 1096:1150 Evaluation of these compounds by enzyme kinetic methods against hOGA and hHexB revealed potent nanomolar competitive inhibition of both enzymes, with no significant selectivity towards either. 35162960 9 56 theme QM/MM 1496:1500 arg1 optimizations 1502:1514 Prime protein-ligand refinement and QM/MM optimizations 1460:1514 optimizations 1502:1514 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 2 57 theme enzymes 480:486 arg1 inhibition 460:469 selective inhibition 450:469 selective inhibition of these enzymes 450:486 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 6 58 theme nanomolar 1103:1111 arg1 inhibition 1125:1134 potent nanomolar competitive inhibition 1096:1134 potent nanomolar competitive inhibition of both enzymes 1096:1150 Evaluation of these compounds by enzyme kinetic methods against hOGA and hHexB revealed potent nanomolar competitive inhibition of both enzymes, with no significant selectivity towards either. 35162960 1 59 link O-linked 156:163 arg1 enzyme 204:209 the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme 146:209 enzyme 204:209 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 7 60 theme = 1323:1323 arg1 nM 1328:1329 Ki = 27 nM 1320:1329 Ki = 27 nM 1320:1329 The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). 35162960 3 61 theme inhibitors 598:607 arg1 relationships 577:589 the structure-activity relationships 554:589 the structure-activity relationships of OGA inhibitors 554:607 In order to extend the structure-activity relationships of OGA inhibitors, a series of 2-acetamido-2-deoxy-d-glucono-1,5-lactone sulfonylhydrazones was prepared from d-glucosamine. 35162960 1 62 from diseases 252:259 arg1 relevant 232:239 relevant 232:239 relevant 232:239 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 1 63 from relevant 232:239 arg1 diabetes 324:331 type 2 diabetes 317:331 type 2 diabetes 317:331 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 1 63 from relevant 232:239 arg1 cancer 338:343 cancer 338:343 cancer 338:343 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 1 63 from relevant 232:239 arg1 diseases 252:259 several diseases 244:259 several diseases such as neurodegenerative and cardiovascular disorders 244:314 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 1 63 from relevant 232:239 arg1 disorders 306:314 neurodegenerative and cardiovascular disorders 269:314 disorders 306:314 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 1 64 theme human 150:154 arg1 enzyme 204:209 the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme 146:209 enzyme 204:209 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 7 65 theme efficient 1210:1218 arg1 inhibitor 1220:1228 The most efficient inhibitor 1201:1228 The most efficient inhibitor of hOGA 1201:1236 The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). 35162960 7 65 theme efficient 1210:1218 arg1 1-naphthalenesulfonylhydrazone 1284:1313 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone 1242:1313 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM) 1242:1330 The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). 35162960 7 66 dep 5f 1316:1317 arg1 nM 1328:1329 Ki = 27 nM 1320:1329 Ki = 27 nM 1320:1329 The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). 35162960 1 67 theme O-linked 156:163 arg1 enzyme 204:209 the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme 146:209 enzyme 204:209 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 2 68 theme applications 521:532 arg1 terms 502:506 terms 502:506 terms of potential applications 502:532 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 9 69 theme computational 1437:1449 arg1 studies 1451:1457 computational studies 1437:1457 computational studies (Prime protein-ligand refinement and QM/MM optimizations) 1437:1515 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 0 70 dep Sulfonylhydrazones 42:59 arg1 Evaluation 76:85 Evaluation 76:85 Evaluation 76:85 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 35162960 0 70 dep Sulfonylhydrazones 42:59 arg1 Synthesis 62:70 Synthesis 62:70 Synthesis 62:70 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 35162960 0 70 dep Sulfonylhydrazones 42:59 arg1 Sulfonylhydrazones 42:59 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones 0:59 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 0:130 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. 35162960 1 71 theme β-N-acetylglucosaminidase 165:189 arg1 enzyme 204:209 the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme 146:209 enzyme 204:209 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 35162960 2 72 theme potential 511:519 arg1 applications 521:532 potential applications 511:532 potential applications 511:532 Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. 35162960 9 73 theme glucono-1,5-lactone 1579:1597 arg1 sulfonylhydrazones 1599:1616 the glucono-1,5-lactone sulfonylhydrazones 1575:1616 the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation 1575:1641 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 9 74 from conformation 1630:1641 arg1 preference 1561:1570 the binding preference 1549:1570 the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds 1549:1664 To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds. 35162960 4 75 theme N-acetyl-3,4,6-tri-O-acetyl-d-glucosamine 764:804 arg1 condensation 748:759 condensation 748:759 condensation of N-acetyl-3,4,6-tri-O-acetyl-d-glucosamine with arenesulfonylhydrazines 748:833 The synthetic sequence involved condensation of N-acetyl-3,4,6-tri-O-acetyl-d-glucosamine with arenesulfonylhydrazines, followed by MnO2 oxidation to the corresponding glucono-1,5-lactone sulfonylhydrazones. 35162960 1 76 theme neurodegenerative 269:285 arg1 disorders 306:314 neurodegenerative and cardiovascular disorders 269:314 disorders 306:314 Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. 33593071 10 0 theme disrupted 1657:1665 arg1 energetics 1681:1690 disrupted mitochondrial energetics 1657:1690 disrupted mitochondrial energetics 1657:1690 Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. 33593071 11 1 theme Complex 1766:1772 arg1 activity 1776:1783 Complex I activity 1766:1783 Complex I activity 1766:1783 Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in O-GlcNAc-mediated cardiac pathology. 33593071 5 2 dep METHODS 802:808 arg1 developed 813:821 developed 813:821 developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress 813:957 METHODS We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress. 33593071 13 3 theme pathologic 2198:2207 arg1 remodeling 2209:2218 pressure overload-induced pathologic remodeling 2172:2218 pressure overload-induced pathologic remodeling 2172:2218 Enhanced OGA activity is well tolerated and attenuation of O-GlcNAcylation is beneficial against pressure overload-induced pathologic remodeling and heart failure. 33593071 10 4 theme complex 1711:1717 arg1 I 1719:1719 complex I 1711:1719 complex I activity 1711:1728 Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. 33593071 11 5 theme OGA 1800:1802 arg1 interbreeding 1815:1827 OGA transgenic interbreeding 1800:1827 OGA transgenic interbreeding 1800:1827 Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in O-GlcNAc-mediated cardiac pathology. 33593071 7 6 theme OGA 1141:1143 arg1 hearts 1156:1161 OGA transgenic hearts 1141:1161 OGA transgenic hearts 1141:1161 In contrast, OGA transgenic hearts had lower O-GlcNAcylation but identical cardiac function to wild-type littermate controls. 33593071 2 7 theme β-N-acetylglucosamine 257:277 arg1 moieties 290:297 O-linked β-N-acetylglucosamine [O-GlcNAc] moieties 248:297 O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins 248:349 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 5 8 theme myocardial 858:867 arg1 overexpression 869:882 myocardial overexpression 858:882 myocardial overexpression of OGT and OGA 858:897 METHODS We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress. 33593071 10 9 from mice 1760:1763 arg1 hearts 1733:1738 hearts 1733:1738 hearts from OGT transgenic mice 1733:1763 Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. 33593071 4 10 theme Failing 645:651 arg1 myocardium 653:662 Failing myocardium 645:662 Failing myocardium 645:662 Failing myocardium is marked by increased O-GlcNAcylation, but whether excessive O-GlcNAcylation contributes to cardiomyopathy and heart failure is unknown. 33593071 1 11 theme obesity 176:182 arg1 prevalence 162:171 the rising prevalence 151:171 the rising prevalence of obesity, hypertension, and diabetes 151:210 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 10 12 theme activity 1721:1728 arg1 impairment 1697:1706 impairment 1697:1706 impairment of complex I activity 1697:1728 Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. 33593071 5 13 theme transgenic 829:838 arg1 models 846:851 2 new transgenic mouse models 823:851 2 new transgenic mouse models 823:851 METHODS We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress. 33593071 8 14 theme transgenic 1258:1267 arg1 hearts 1269:1274 OGA transgenic hearts 1254:1274 OGA transgenic hearts 1254:1274 OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. 33593071 1 15 theme death 112:116 arg1 worldwide 118:126 death worldwide 112:126 death worldwide 112:126 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 7 16 theme identical 1193:1201 arg1 function 1211:1218 identical cardiac function 1193:1218 identical cardiac function 1193:1218 In contrast, OGA transgenic hearts had lower O-GlcNAcylation but identical cardiac function to wild-type littermate controls. 33593071 8 17 theme attenuated 1346:1355 arg1 levels 1384:1389 attenuated myocardial O-GlcNAcylation levels 1346:1389 attenuated myocardial O-GlcNAcylation levels 1346:1389 OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. 33593071 10 18 theme OGT 1745:1747 arg1 mice 1760:1763 OGT transgenic mice 1745:1763 OGT transgenic mice 1745:1763 Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. 33593071 14 19 theme excessive 2282:2290 arg1 O-GlcNAcylation 2292:2306 excessive O-GlcNAcylation 2282:2306 excessive O-GlcNAcylation 2282:2306 These findings suggest that attenuation of excessive O-GlcNAcylation may represent a novel therapeutic approach for cardiomyopathy. 33593071 9 20 theme OGT 1605:1607 arg1 elevation 1581:1589 persistent elevation 1570:1589 persistent elevation of myocardial OGT 1570:1607 Interbreeding OGT with OGA transgenic mice rescued cardiomyopathy and premature death, despite persistent elevation of myocardial OGT. 33593071 13 21 theme O-GlcNAcylation 2134:2148 arg1 attenuation 2119:2129 attenuation 2119:2129 attenuation of O-GlcNAcylation 2119:2148 Enhanced OGA activity is well tolerated and attenuation of O-GlcNAcylation is beneficial against pressure overload-induced pathologic remodeling and heart failure. 33593071 8 22 theme O-GlcNAcylation 1368:1382 arg1 levels 1384:1389 attenuated myocardial O-GlcNAcylation levels 1346:1389 attenuated myocardial O-GlcNAcylation levels 1346:1389 OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. 33593071 13 23 theme OGA 2084:2086 arg1 activity 2088:2095 Enhanced OGA activity 2075:2095 Enhanced OGA activity 2075:2095 Enhanced OGA activity is well tolerated and attenuation of O-GlcNAcylation is beneficial against pressure overload-induced pathologic remodeling and heart failure. 33593071 5 24 theme independent 926:936 arg1 O-GlcNAcylation 910:924 O-GlcNAcylation 910:924 O-GlcNAcylation independent of pathologic stress 910:957 METHODS We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress. 33593071 3 25 dep activity 572:579 arg1 addition 552:559 addition 552:559 addition 552:559 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 6 26 dep showed 1004:1009 arg1 increased 1011:1019 increased 1011:1019 increased O-GlcNAcylation 1011:1035 RESULTS We found that OGT transgenic hearts showed increased O-GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death. 33593071 6 26 dep showed 1004:1009 arg1 developed 1041:1049 developed 1041:1049 developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death 1041:1125 RESULTS We found that OGT transgenic hearts showed increased O-GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death. 33593071 14 27 theme therapeutic 2330:2340 arg1 approach 2342:2349 a novel therapeutic approach 2322:2349 a novel therapeutic approach for cardiomyopathy 2322:2368 These findings suggest that attenuation of excessive O-GlcNAcylation may represent a novel therapeutic approach for cardiomyopathy. 33593071 8 28 theme pathologic 1418:1427 arg1 hypertrophy 1429:1439 decreased pathologic hypertrophy 1408:1439 decreased pathologic hypertrophy 1408:1439 OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. 33593071 2 29 link O-linked 248:255 arg1 moieties 290:297 O-linked β-N-acetylglucosamine [O-GlcNAc] moieties 248:297 O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins 248:349 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 1 30 theme BACKGROUND 65:74 arg1 failure 82:88 BACKGROUND Heart failure 65:88 BACKGROUND Heart failure 65:88 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 1 30 theme BACKGROUND 65:74 arg1 cause 103:107 a leading cause 93:107 a leading cause of death worldwide 93:126 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 6 31 theme transgenic 986:995 arg1 hearts 997:1002 OGT transgenic hearts 982:1002 OGT transgenic hearts 982:1002 RESULTS We found that OGT transgenic hearts showed increased O-GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death. 33593071 4 32 theme heart 776:780 arg1 failure 782:788 heart failure 776:788 heart failure 776:788 Failing myocardium is marked by increased O-GlcNAcylation, but whether excessive O-GlcNAcylation contributes to cardiomyopathy and heart failure is unknown. 33593071 2 33 theme proteins 405:412 arg1 O-GlcNAcylation 213:227 O-GlcNAcylation 213:227 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) 213:350 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 2 33 theme proteins 405:412 arg1 modification 375:386 a posttranslational modification 355:386 a posttranslational modification of intracellular proteins 355:412 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 7 34 theme littermate 1233:1242 arg1 controls 1244:1251 wild-type littermate controls 1223:1251 wild-type littermate controls 1223:1251 In contrast, OGA transgenic hearts had lower O-GlcNAcylation but identical cardiac function to wild-type littermate controls. 33593071 2 35 theme cellular 453:460 arg1 stress 462:467 cellular stress 453:467 cellular stress 453:467 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 4 36 theme excessive 716:724 arg1 O-GlcNAcylation 726:740 excessive O-GlcNAcylation 716:740 excessive O-GlcNAcylation 716:740 Failing myocardium is marked by increased O-GlcNAcylation, but whether excessive O-GlcNAcylation contributes to cardiomyopathy and heart failure is unknown. 33593071 0 37 theme Excessive 0:8 arg1 O-GlcNAcylation 10:24 Excessive O-GlcNAcylation 0:24 Excessive O-GlcNAcylation 0:24 Excessive O-GlcNAcylation Causes Heart Failure and Sudden Death. 33593071 5 38 theme stress 952:957 arg1 independent 926:936 independent 926:936 independent 926:936 METHODS We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress. 33593071 10 39 theme Transcriptomic 1610:1623 arg1 studies 1640:1646 Transcriptomic and functional studies 1610:1646 Transcriptomic and functional studies 1610:1646 Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. 33593071 3 40 theme Total 470:474 arg1 levels 476:481 Total levels 470:481 Total levels of O-GlcNAcylation 470:500 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 7 41 theme cardiac 1203:1209 arg1 function 1211:1218 identical cardiac function 1193:1218 identical cardiac function 1193:1218 In contrast, OGA transgenic hearts had lower O-GlcNAcylation but identical cardiac function to wild-type littermate controls. 33593071 12 42 theme excessive 1970:1978 arg1 O-GlcNAcylation 1980:1994 excessive O-GlcNAcylation 1970:1994 excessive O-GlcNAcylation 1970:1994 CONCLUSIONS Our data provide evidence that excessive O-GlcNAcylation causes cardiomyopathy, at least in part, attributable to defective energetics. 33593071 6 43 theme dilated 1058:1064 arg1 cardiomyopathy 1066:1079 severe dilated cardiomyopathy 1051:1079 severe dilated cardiomyopathy 1051:1079 RESULTS We found that OGT transgenic hearts showed increased O-GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death. 33593071 11 44 from role 1854:1857 arg1 pathology 1916:1924 O-GlcNAc-mediated cardiac pathology 1890:1924 O-GlcNAc-mediated cardiac pathology 1890:1924 Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in O-GlcNAc-mediated cardiac pathology. 33593071 7 45 theme lower 1167:1171 arg1 O-GlcNAcylation 1173:1187 lower O-GlcNAcylation 1167:1187 lower O-GlcNAcylation 1167:1187 In contrast, OGA transgenic hearts had lower O-GlcNAcylation but identical cardiac function to wild-type littermate controls. 33593071 10 46 theme functional 1629:1638 arg1 studies 1640:1646 Transcriptomic and functional studies 1610:1646 Transcriptomic and functional studies 1610:1646 Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. 33593071 11 47 theme mitochondrial 1863:1875 arg1 complex 1877:1883 mitochondrial complex I 1863:1885 mitochondrial complex I 1863:1885 Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in O-GlcNAc-mediated cardiac pathology. 33593071 9 48 theme Interbreeding 1475:1487 arg1 OGT 1489:1491 Interbreeding OGT 1475:1491 Interbreeding OGT with OGA transgenic mice 1475:1516 Interbreeding OGT with OGA transgenic mice rescued cardiomyopathy and premature death, despite persistent elevation of myocardial OGT. 33593071 13 49 theme pressure 2172:2179 arg1 remodeling 2209:2218 pressure overload-induced pathologic remodeling 2172:2218 pressure overload-induced pathologic remodeling 2172:2218 Enhanced OGA activity is well tolerated and attenuation of O-GlcNAcylation is beneficial against pressure overload-induced pathologic remodeling and heart failure. 33593071 2 50 theme posttranslational 357:373 arg1 O-GlcNAcylation 213:227 O-GlcNAcylation 213:227 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) 213:350 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 2 50 theme posttranslational 357:373 arg1 modification 375:386 a posttranslational modification 355:386 a posttranslational modification of intracellular proteins 355:412 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 9 51 theme premature 1545:1553 arg1 death 1555:1559 premature death 1545:1559 premature death 1545:1559 Interbreeding OGT with OGA transgenic mice rescued cardiomyopathy and premature death, despite persistent elevation of myocardial OGT. 33593071 10 52 theme mitochondrial 1667:1679 arg1 energetics 1681:1690 disrupted mitochondrial energetics 1657:1690 disrupted mitochondrial energetics 1657:1690 Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. 33593071 7 53 theme transgenic 1145:1154 arg1 hearts 1156:1161 OGA transgenic hearts 1141:1161 OGA transgenic hearts 1141:1161 In contrast, OGA transgenic hearts had lower O-GlcNAcylation but identical cardiac function to wild-type littermate controls. 33593071 9 54 with OGT 1489:1491 arg1 mice 1513:1516 OGA transgenic mice 1498:1516 OGA transgenic mice 1498:1516 Interbreeding OGT with OGA transgenic mice rescued cardiomyopathy and premature death, despite persistent elevation of myocardial OGT. 33593071 9 55 theme transgenic 1502:1511 arg1 mice 1513:1516 OGA transgenic mice 1498:1516 OGA transgenic mice 1498:1516 Interbreeding OGT with OGA transgenic mice rescued cardiomyopathy and premature death, despite persistent elevation of myocardial OGT. 33593071 10 56 theme I 1719:1719 arg1 activity 1721:1728 complex I activity 1711:1728 complex I activity 1711:1728 Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. 33593071 11 57 theme I 1774:1774 arg1 activity 1776:1783 Complex I activity 1766:1783 Complex I activity 1766:1783 Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in O-GlcNAc-mediated cardiac pathology. 33593071 7 58 contain had 1163:1165 arg2 function 1211:1218 identical cardiac function 1193:1218 identical cardiac function 1193:1218 In contrast, OGA transgenic hearts had lower O-GlcNAcylation but identical cardiac function to wild-type littermate controls. 33593071 7 58 contain had 1163:1165 arg2 O-GlcNAcylation 1173:1187 lower O-GlcNAcylation 1167:1187 lower O-GlcNAcylation 1167:1187 In contrast, OGA transgenic hearts had lower O-GlcNAcylation but identical cardiac function to wild-type littermate controls. 33593071 7 58 contain had 1163:1165 arg1 hearts 1156:1161 OGA transgenic hearts 1141:1161 OGA transgenic hearts 1141:1161 In contrast, OGA transgenic hearts had lower O-GlcNAcylation but identical cardiac function to wild-type littermate controls. 33593071 2 59 theme moieties 290:297 arg1 attachment 234:243 the attachment 230:243 the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins 230:349 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 2 60 theme nuclear 315:321 arg1 proteins 342:349 cytoplasmic, nuclear, and mitochondrial proteins 302:349 cytoplasmic, nuclear, and mitochondrial proteins 302:349 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 11 61 theme transgenic 1804:1813 arg1 interbreeding 1815:1827 OGA transgenic interbreeding 1800:1827 OGA transgenic interbreeding 1800:1827 Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in O-GlcNAc-mediated cardiac pathology. 33593071 2 62 theme [O-GlcNAc 279:287 arg1 moieties 290:297 O-linked β-N-acetylglucosamine [O-GlcNAc] moieties 248:297 O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins 248:349 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 1 63 theme rising 155:160 arg1 prevalence 162:171 the rising prevalence 151:171 the rising prevalence of obesity, hypertension, and diabetes 151:210 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 0 64 theme Sudden 51:56 arg1 Death 58:62 Sudden Death 51:62 Sudden Death 51:62 Excessive O-GlcNAcylation Causes Heart Failure and Sudden Death. 33593071 3 65 theme net 568:570 arg1 activity 572:579 the net activity 564:579 the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) 564:642 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 3 66 dep enzymes 586:592 arg1 O-GlcNAcase 626:636 O-GlcNAcase 626:636 O-GlcNAcase (OGA) 626:642 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 3 66 dep enzymes 586:592 arg1 transferase 604:614 O-GlcNAc transferase 595:614 O-GlcNAc transferase (OGT) 595:620 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 3 66 dep enzymes 586:592 arg1 enzymes 586:592 2 enzymes 584:592 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) 584:642 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 3 66 dep enzymes 586:592 arg1 OGA 639:641 OGA 639:641 OGA 639:641 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 3 66 dep enzymes 586:592 arg1 OGT 617:619 OGT 617:619 OGT 617:619 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 6 67 theme OGT 982:984 arg1 hearts 997:1002 OGT transgenic hearts 982:1002 OGT transgenic hearts 982:1002 RESULTS We found that OGT transgenic hearts showed increased O-GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death. 33593071 8 68 theme pathologic 1294:1303 arg1 stress 1305:1310 pathologic stress 1294:1310 pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels 1294:1389 OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. 33593071 2 69 theme cytoplasmic 302:312 arg1 proteins 342:349 cytoplasmic, nuclear, and mitochondrial proteins 302:349 cytoplasmic, nuclear, and mitochondrial proteins 302:349 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 9 70 theme persistent 1570:1579 arg1 elevation 1581:1589 persistent elevation 1570:1589 persistent elevation of myocardial OGT 1570:1607 Interbreeding OGT with OGA transgenic mice rescued cardiomyopathy and premature death, despite persistent elevation of myocardial OGT. 33593071 3 71 theme enzymes 586:592 arg1 activity 572:579 the net activity 564:579 the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) 564:642 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 5 72 theme mouse 840:844 arg1 models 846:851 2 new transgenic mouse models 823:851 2 new transgenic mouse models 823:851 METHODS We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress. 33593071 8 73 theme OGA 1254:1256 arg1 hearts 1269:1274 OGA transgenic hearts 1254:1274 OGA transgenic hearts 1254:1274 OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. 33593071 6 74 dep RESULTS 960:966 arg1 found 971:975 found 971:975 found that OGT transgenic hearts showed increased O-GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death 971:1125 RESULTS We found that OGT transgenic hearts showed increased O-GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death. 33593071 8 75 theme pressure 1323:1330 arg1 overload 1332:1339 pressure overload 1323:1339 pressure overload 1323:1339 OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. 33593071 10 76 theme transgenic 1749:1758 arg1 mice 1760:1763 OGT transgenic mice 1745:1763 OGT transgenic mice 1745:1763 Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. 33593071 8 77 theme wild-type 1455:1463 arg1 controls 1465:1472 wild-type controls 1455:1472 wild-type controls 1455:1472 OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. 33593071 9 78 theme myocardial 1594:1603 arg1 OGT 1605:1607 myocardial OGT 1594:1607 myocardial OGT 1594:1607 Interbreeding OGT with OGA transgenic mice rescued cardiomyopathy and premature death, despite persistent elevation of myocardial OGT. 33593071 4 79 theme increased 677:685 arg1 O-GlcNAcylation 687:701 increased O-GlcNAcylation 677:701 increased O-GlcNAcylation 677:701 Failing myocardium is marked by increased O-GlcNAcylation, but whether excessive O-GlcNAcylation contributes to cardiomyopathy and heart failure is unknown. 33593071 13 80 theme Enhanced 2075:2082 arg1 activity 2088:2095 Enhanced OGA activity 2075:2095 Enhanced OGA activity 2075:2095 Enhanced OGA activity is well tolerated and attenuation of O-GlcNAcylation is beneficial against pressure overload-induced pathologic remodeling and heart failure. 33593071 2 81 theme O-linked 248:255 arg1 moieties 290:297 O-linked β-N-acetylglucosamine [O-GlcNAc] moieties 248:297 O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins 248:349 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 1 82 theme worldwide 118:126 arg1 failure 82:88 BACKGROUND Heart failure 65:88 BACKGROUND Heart failure 65:88 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 1 82 theme worldwide 118:126 arg1 cause 103:107 a leading cause 93:107 a leading cause of death worldwide 93:126 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 6 83 theme severe 1051:1056 arg1 cardiomyopathy 1066:1079 severe dilated cardiomyopathy 1051:1079 severe dilated cardiomyopathy 1051:1079 RESULTS We found that OGT transgenic hearts showed increased O-GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death. 33593071 8 84 theme myocardial 1357:1366 arg1 levels 1384:1389 attenuated myocardial O-GlcNAcylation levels 1346:1389 attenuated myocardial O-GlcNAcylation levels 1346:1389 OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. 33593071 11 85 theme O-GlcNAc-mediated 1890:1906 arg1 pathology 1916:1924 O-GlcNAc-mediated cardiac pathology 1890:1924 O-GlcNAc-mediated cardiac pathology 1890:1924 Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in O-GlcNAc-mediated cardiac pathology. 33593071 3 86 theme O-GlcNAc 595:602 arg1 enzymes 586:592 2 enzymes 584:592 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) 584:642 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 3 86 theme O-GlcNAc 595:602 arg1 transferase 604:614 O-GlcNAc transferase 595:614 O-GlcNAc transferase (OGT) 595:620 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 3 86 theme O-GlcNAc 595:602 arg1 OGT 617:619 OGT 617:619 OGT 617:619 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 5 87 theme new 825:827 arg1 models 846:851 2 new transgenic mouse models 823:851 2 new transgenic mouse models 823:851 METHODS We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress. 33593071 5 88 theme OGT 887:889 arg1 overexpression 869:882 myocardial overexpression 858:882 myocardial overexpression of OGT and OGA 858:897 METHODS We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress. 33593071 11 89 theme cardiac 1908:1914 arg1 pathology 1916:1924 O-GlcNAc-mediated cardiac pathology 1890:1924 O-GlcNAc-mediated cardiac pathology 1890:1924 Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in O-GlcNAc-mediated cardiac pathology. 33593071 1 90 theme diabetes 203:210 arg1 prevalence 162:171 the rising prevalence 151:171 the rising prevalence of obesity, hypertension, and diabetes 151:210 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 12 91 dep CONCLUSIONS 1927:1937 arg1 provide 1948:1954 provide 1948:1954 provide evidence that excessive O-GlcNAcylation causes cardiomyopathy, at least in part, attributable to defective energetics 1948:2072 CONCLUSIONS Our data provide evidence that excessive O-GlcNAcylation causes cardiomyopathy, at least in part, attributable to defective energetics. 33593071 5 92 theme OGA 895:897 arg1 overexpression 869:882 myocardial overexpression 858:882 myocardial overexpression of OGT and OGA 858:897 METHODS We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress. 33593071 14 93 theme novel 2324:2328 arg1 approach 2342:2349 a novel therapeutic approach 2322:2349 a novel therapeutic approach for cardiomyopathy 2322:2368 These findings suggest that attenuation of excessive O-GlcNAcylation may represent a novel therapeutic approach for cardiomyopathy. 33593071 8 94 theme decreased 1408:1416 arg1 hypertrophy 1429:1439 decreased pathologic hypertrophy 1408:1439 decreased pathologic hypertrophy 1408:1439 OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O-GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. 33593071 7 95 theme wild-type 1223:1231 arg1 controls 1244:1251 wild-type littermate controls 1223:1251 wild-type littermate controls 1223:1251 In contrast, OGA transgenic hearts had lower O-GlcNAcylation but identical cardiac function to wild-type littermate controls. 33593071 12 96 theme defective 2053:2061 arg1 energetics 2063:2072 defective energetics 2053:2072 defective energetics 2053:2072 CONCLUSIONS Our data provide evidence that excessive O-GlcNAcylation causes cardiomyopathy, at least in part, attributable to defective energetics. 33593071 1 97 theme hypertension 185:196 arg1 prevalence 162:171 the rising prevalence 151:171 the rising prevalence of obesity, hypertension, and diabetes 151:210 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 1 98 theme Heart 76:80 arg1 failure 82:88 BACKGROUND Heart failure 65:88 BACKGROUND Heart failure 65:88 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 1 98 theme Heart 76:80 arg1 cause 103:107 a leading cause 93:107 a leading cause of death worldwide 93:126 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 6 99 theme premature 1111:1119 arg1 death 1121:1125 premature death 1111:1125 premature death 1111:1125 RESULTS We found that OGT transgenic hearts showed increased O-GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death. 33593071 2 100 theme intracellular 391:403 arg1 proteins 405:412 intracellular proteins 391:412 intracellular proteins 391:412 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 5 101 theme pathologic 941:950 arg1 stress 952:957 pathologic stress 941:957 pathologic stress 941:957 METHODS We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O-GlcNAcylation independent of pathologic stress. 33593071 14 102 theme O-GlcNAcylation 2292:2306 arg1 attenuation 2267:2277 attenuation 2267:2277 attenuation of excessive O-GlcNAcylation 2267:2306 These findings suggest that attenuation of excessive O-GlcNAcylation may represent a novel therapeutic approach for cardiomyopathy. 33593071 0 103 theme Heart 33:37 arg1 Failure 39:45 Heart Failure 33:45 Heart Failure 33:45 Excessive O-GlcNAcylation Causes Heart Failure and Sudden Death. 33593071 1 104 theme leading 95:101 arg1 failure 82:88 BACKGROUND Heart failure 65:88 BACKGROUND Heart failure 65:88 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 1 104 theme leading 95:101 arg1 cause 103:107 a leading cause 93:107 a leading cause of death worldwide 93:126 BACKGROUND Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. 33593071 6 105 theme ventricular 1082:1092 arg1 arrhythmias 1094:1104 ventricular arrhythmias 1082:1104 ventricular arrhythmias 1082:1104 RESULTS We found that OGT transgenic hearts showed increased O-GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death. 33593071 2 106 theme metabolic 430:438 arg1 O-GlcNAcylation 213:227 O-GlcNAcylation 213:227 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) 213:350 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 2 106 theme metabolic 430:438 arg1 rheostat 440:447 a metabolic rheostat 428:447 a metabolic rheostat for cellular stress 428:467 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 13 107 theme heart 2224:2228 arg1 failure 2230:2236 heart failure 2224:2236 heart failure 2224:2236 Enhanced OGA activity is well tolerated and attenuation of O-GlcNAcylation is beneficial against pressure overload-induced pathologic remodeling and heart failure. 33593071 2 108 theme mitochondrial 328:340 arg1 proteins 342:349 cytoplasmic, nuclear, and mitochondrial proteins 302:349 cytoplasmic, nuclear, and mitochondrial proteins 302:349 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 11 109 theme important 1844:1852 arg1 role 1854:1857 an important role 1841:1857 an important role for mitochondrial complex I in O-GlcNAc-mediated cardiac pathology 1841:1924 Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in O-GlcNAc-mediated cardiac pathology. 33593071 3 110 theme O-GlcNAcylation 486:500 arg1 levels 476:481 Total levels 470:481 Total levels of O-GlcNAcylation 470:500 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 2 111 dep O-GlcNAcylation 213:227 arg1 attachment 234:243 the attachment 230:243 the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins 230:349 O-GlcNAcylation (the attachment of O-linked β-N-acetylglucosamine [O-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. 33593071 13 112 theme overload-induced 2181:2196 arg1 remodeling 2209:2218 pressure overload-induced pathologic remodeling 2172:2218 pressure overload-induced pathologic remodeling 2172:2218 Enhanced OGA activity is well tolerated and attenuation of O-GlcNAcylation is beneficial against pressure overload-induced pathologic remodeling and heart failure. 33593071 3 113 theme metabolic 533:541 arg1 flux 543:546 metabolic flux 533:546 metabolic flux 533:546 Total levels of O-GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). 33593071 9 114 theme OGA 1498:1500 arg1 mice 1513:1516 OGA transgenic mice 1498:1516 OGA transgenic mice 1498:1516 Interbreeding OGT with OGA transgenic mice rescued cardiomyopathy and premature death, despite persistent elevation of myocardial OGT. 37126482 4 0 theme sialic 933:938 arg1 conjugates 945:954 model isomeric sialic acid conjugates 918:954 model isomeric sialic acid conjugates 918:954 These chemical modifications were validated and structurally characterized using model isomeric sialic acid conjugates and model protein carriers. 37126482 1 1 theme chemical 242:249 arg1 properties 281:290 distinct chemical, biological, and pathological properties 233:290 distinct chemical, biological, and pathological properties 233:290 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 7 2 theme alkyne-modified 1465:1479 arg1 N-glycans 1505:1513 alkyne-modified α2,3-linked sialic acid N-glycans 1465:1513 alkyne-modified α2,3-linked sialic acid N-glycans 1465:1513 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 6 3 theme glycan 1249:1254 arg1 isomers 1268:1274 N-linked glycan sialic acid isomers 1240:1274 N-linked glycan sialic acid isomers 1240:1274 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 3 4 theme chemistry 763:771 arg1 alkyne 773:778 bioorthogonal click chemistry alkyne or azide groups 743:794 alkyne 773:778 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 10 5 theme sialic 1900:1905 arg1 glycans 1923:1929 sialic acid-containing glycans 1900:1929 sialic acid-containing glycans 1900:1929 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 37126482 1 6 theme biological 252:261 arg1 properties 281:290 distinct chemical, biological, and pathological properties 233:290 distinct chemical, biological, and pathological properties 233:290 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 3 7 theme bioorthogonal 743:755 arg1 alkyne 773:778 bioorthogonal click chemistry alkyne or azide groups 743:794 alkyne 773:778 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 10 8 theme reagents 1886:1893 arg1 introduction 1840:1851 The direct chemical introduction 1820:1851 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins 1820:1947 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 37126482 4 9 theme model 918:922 arg1 conjugates 945:954 model isomeric sialic acid conjugates 918:954 model isomeric sialic acid conjugates 918:954 These chemical modifications were validated and structurally characterized using model isomeric sialic acid conjugates and model protein carriers. 37126482 3 10 theme groups 789:794 arg1 introduction 727:738 the introduction 723:738 the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids 723:834 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 7 11 theme N-glycans 1505:1513 arg1 distribution 1449:1460 distribution 1449:1460 distribution 1449:1460 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 7 11 theme N-glycans 1505:1513 arg1 numbers 1437:1443 numbers 1437:1443 numbers 1437:1443 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 9 12 theme azide 1689:1693 arg1 amine 1695:1699 the azide amine 1685:1699 the azide amine 1685:1699 Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. 37126482 1 13 theme spectrometry 366:377 arg1 experiments 379:389 traditional mass spectrometry experiments 349:389 traditional mass spectrometry experiments 349:389 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 2 14 theme liquid 565:570 arg1 chromatography 572:585 high-performance liquid chromatography 548:585 high-performance liquid chromatography 548:585 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 7 15 theme sialic 1493:1498 arg1 acid 1500:1503 α2,3-linked sialic acid 1481:1503 alkyne-modified α2,3-linked sialic acid N-glycans 1465:1513 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 3 16 theme α2,8-linked 811:821 arg1 acids 830:834 α2,3- and α2,8-linked sialic acids 801:834 α2,3- and α2,8-linked sialic acids 801:834 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 10 17 theme glycomic 1964:1971 arg1 tool 1973:1976 a new glycomic tool 1958:1976 a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment 1958:2062 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 37126482 4 18 theme model 960:964 arg1 carriers 974:981 model protein carriers 960:981 model protein carriers 960:981 These chemical modifications were validated and structurally characterized using model isomeric sialic acid conjugates and model protein carriers. 37126482 8 19 theme glycol 1561:1566 arg1 linker 1569:1574 a poly(ethylene glycol) linker 1545:1574 a poly(ethylene glycol) linker 1545:1574 An azide-amine compound with a poly(ethylene glycol) linker was evaluated for use in histochemical staining. 37126482 6 20 theme mass 1287:1290 arg1 approaches 1305:1314 mass spectrometry approaches 1287:1314 mass spectrometry approaches 1287:1314 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 3 21 theme α2,3- 801:805 arg1 acids 830:834 α2,3- and α2,8-linked sialic acids 801:834 α2,3- and α2,8-linked sialic acids 801:834 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 0 22 theme Biofluids 137:145 arg1 Spectrometry 101:112 N-Glycan MALDI Imaging Mass Spectrometry 73:112 N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids 73:145 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 5 23 theme α2,3-linked 1111:1121 arg1 glycoproteins 1135:1147 α2,3-linked sialic acid glycoproteins 1111:1147 α2,3-linked sialic acid glycoproteins 1111:1147 Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. 37126482 5 24 theme acid 1130:1133 arg1 glycoproteins 1135:1147 α2,3-linked sialic acid glycoproteins 1111:1147 α2,3-linked sialic acid glycoproteins 1111:1147 Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. 37126482 10 25 theme acid-containing 1907:1921 arg1 glycans 1923:1929 sialic acid-containing glycans 1900:1929 sialic acid-containing glycans 1900:1929 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 37126482 5 26 link α2,3-linked 1111:1121 arg1 glycoproteins 1135:1147 α2,3-linked sialic acid glycoproteins 1111:1147 α2,3-linked sialic acid glycoproteins 1111:1147 Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. 37126482 6 27 theme acid 1263:1266 arg1 isomers 1268:1274 N-linked glycan sialic acid isomers 1240:1274 N-linked glycan sialic acid isomers 1240:1274 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 9 28 dep amine 1695:1699 arg1 isomers 1766:1772 isomers 1766:1772 isomers 1766:1772 Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. 37126482 8 29 from use 1594:1596 arg1 staining 1615:1622 histochemical staining 1601:1622 histochemical staining 1601:1622 An azide-amine compound with a poly(ethylene glycol) linker was evaluated for use in histochemical staining. 37126482 9 30 theme Formalin-fixed 1625:1638 arg1 tissues 1658:1664 Formalin-fixed pancreatic cancer tissues 1625:1664 Formalin-fixed pancreatic cancer tissues 1625:1664 Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. 37126482 2 31 theme acid 498:501 arg1 isomers 503:509 sialic acid isomers 491:509 sialic acid isomers 491:509 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 2 32 theme capillary 588:596 arg1 electrophoresis 598:612 capillary electrophoresis 588:612 capillary electrophoresis 588:612 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 0 33 theme MALDI 82:86 arg1 Spectrometry 101:112 N-Glycan MALDI Imaging Mass Spectrometry 73:112 N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids 73:145 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 1 34 theme acid 155:158 arg1 isomers 160:166 Sialic acid isomers 148:166 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini 148:224 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 1 35 attach attached 168:175 arg1 termini 218:224 glycan termini 211:224 glycan termini 211:224 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 1 35 attach attached 168:175 arg2 isomers 160:166 Sialic acid isomers 148:166 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini 148:224 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 1 35 attach attached 168:175 arg3 α2,3 187:190 α2,3 187:190 α2,3 187:190 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 1 35 attach attached 168:175 arg3 α2,6 195:198 α2,6 195:198 α2,6 195:198 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 8 36 theme histochemical 1601:1613 arg1 staining 1615:1622 histochemical staining 1601:1622 histochemical staining 1601:1622 An azide-amine compound with a poly(ethylene glycol) linker was evaluated for use in histochemical staining. 37126482 0 37 theme Mass 96:99 arg1 Spectrometry 101:112 N-Glycan MALDI Imaging Mass Spectrometry 73:112 N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids 73:145 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 2 38 theme glycoconjugate 521:534 arg1 carriers 536:543 their glycoconjugate carriers 515:543 their glycoconjugate carriers 515:543 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 2 39 theme Multiple 392:399 arg1 strategies 416:425 Multiple derivatization strategies 392:425 Multiple derivatization strategies 392:425 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 1 40 theme traditional 349:359 arg1 spectrometry 366:377 traditional mass spectrometry 349:377 traditional mass spectrometry experiments 349:389 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 5 41 theme amidation 1038:1046 arg1 reagent 1048:1054 the second amidation reagent 1027:1054 the second amidation reagent 1027:1054 Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. 37126482 9 42 theme pancreatic 1640:1649 arg1 tissues 1658:1664 Formalin-fixed pancreatic cancer tissues 1625:1664 Formalin-fixed pancreatic cancer tissues 1625:1664 Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. 37126482 0 43 theme Bioorthogonal 0:12 arg1 Probes 32:37 Bioorthogonal Chemical Labeling Probes 0:37 Bioorthogonal Chemical Labeling Probes 0:37 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 10 44 gly glycoproteins 1935:1947 arg1 glycoproteins 1935:1947 glycoproteins 1935:1947 glycoproteins 1935:1947 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 37126482 7 45 dep Formalin-fixed 1317:1330 arg1 paraffin-embedded 1332:1348 paraffin-embedded 1332:1348 paraffin-embedded 1332:1348 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 0 46 theme Labeling 23:30 arg1 Probes 32:37 Bioorthogonal Chemical Labeling Probes 0:37 Bioorthogonal Chemical Labeling Probes 0:37 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 1 47 theme pathological 268:279 arg1 properties 281:290 distinct chemical, biological, and pathological properties 233:290 distinct chemical, biological, and pathological properties 233:290 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 3 48 theme schemes 686:692 arg1 schemes 686:692 novel derivatization schemes 665:692 novel derivatization schemes 665:692 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 3 48 theme schemes 686:692 arg1 set 658:660 a set 656:660 a set of novel derivatization schemes 656:692 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 5 49 theme functional 1089:1098 arg1 group 1100:1104 an alkyne functional group 1079:1104 an alkyne functional group into α2,3-linked sialic acid glycoproteins 1079:1147 Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. 37126482 7 50 theme cell 1396:1399 arg1 lines 1401:1405 pancreatic cancer cell lines 1378:1405 pancreatic cancer cell lines 1378:1405 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 3 51 theme novel 665:669 arg1 schemes 686:692 novel derivatization schemes 665:692 novel derivatization schemes 665:692 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 8 52 theme azide-amine 1519:1529 arg1 compound 1531:1538 An azide-amine compound 1516:1538 An azide-amine compound with a poly(ethylene glycol) linker 1516:1574 An azide-amine compound with a poly(ethylene glycol) linker was evaluated for use in histochemical staining. 37126482 0 53 theme Acid 56:59 arg1 Isomers 61:67 Sialic Acid Isomers 49:67 Sialic Acid Isomers 49:67 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 7 54 theme pancreatic 1378:1387 arg1 lines 1401:1405 pancreatic cancer cell lines 1378:1405 pancreatic cancer cell lines 1378:1405 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 10 55 theme direct 1824:1829 arg1 introduction 1840:1851 The direct chemical introduction 1820:1851 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins 1820:1947 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 37126482 4 56 theme chemical 843:850 arg1 modifications 852:864 These chemical modifications 837:864 These chemical modifications 837:864 These chemical modifications were validated and structurally characterized using model isomeric sialic acid conjugates and model protein carriers. 37126482 10 57 theme chemistry 1876:1884 arg1 reagents 1886:1893 bioorthogonal click chemistry reagents 1856:1893 bioorthogonal click chemistry reagents 1856:1893 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 37126482 7 58 theme prostate 1350:1357 arg1 tissues 1366:1372 Formalin-fixed paraffin-embedded prostate cancer tissues 1317:1372 Formalin-fixed paraffin-embedded prostate cancer tissues 1317:1372 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 10 59 theme bioorthogonal 1856:1868 arg1 reagents 1886:1893 bioorthogonal click chemistry reagents 1856:1893 bioorthogonal click chemistry reagents 1856:1893 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 37126482 1 60 theme distinct 233:240 arg1 properties 281:290 distinct chemical, biological, and pathological properties 233:290 distinct chemical, biological, and pathological properties 233:290 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 4 61 theme isomeric 924:931 arg1 conjugates 945:954 model isomeric sialic acid conjugates 918:954 model isomeric sialic acid conjugates 918:954 These chemical modifications were validated and structurally characterized using model isomeric sialic acid conjugates and model protein carriers. 37126482 7 62 theme Formalin-fixed 1317:1330 arg1 tissues 1366:1372 Formalin-fixed paraffin-embedded prostate cancer tissues 1317:1372 Formalin-fixed paraffin-embedded prostate cancer tissues 1317:1372 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 5 63 gly glycoproteins 1135:1147 arg1 glycoproteins 1135:1147 α2,3-linked sialic acid glycoproteins 1111:1147 α2,3-linked sialic acid glycoproteins 1111:1147 Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. 37126482 9 64 theme sialic 1754:1759 arg1 acid 1761:1764 sialic acid 1754:1764 sialic acid 1754:1764 Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. 37126482 2 65 theme mass 619:622 arg1 spectrometry 624:635 mass spectrometry 619:635 mass spectrometry 619:635 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 6 66 theme N-linked 1240:1247 arg1 isomers 1268:1274 N-linked glycan sialic acid isomers 1240:1274 N-linked glycan sialic acid isomers 1240:1274 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 3 67 theme alkyne 773:778 arg1 introduction 727:738 the introduction 723:738 the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids 723:834 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 2 68 dep chromatography 572:585 arg1 workflows 637:645 workflows 637:645 workflows 637:645 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 9 69 theme streptavidin-peroxidase 1786:1808 arg1 staining 1810:1817 streptavidin-peroxidase staining 1786:1817 streptavidin-peroxidase staining 1786:1817 Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. 37126482 3 70 theme click 757:761 arg1 alkyne 773:778 bioorthogonal click chemistry alkyne or azide groups 743:794 alkyne 773:778 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 6 71 dep detection 1209:1217 arg1 the 1205:1207 the 1205:1207 the 1205:1207 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 0 72 theme Cells 126:130 arg1 Spectrometry 101:112 N-Glycan MALDI Imaging Mass Spectrometry 73:112 N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids 73:145 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 8 73 theme ethylene 1552:1559 arg1 linker 1569:1574 a poly(ethylene glycol) linker 1545:1574 a poly(ethylene glycol) linker 1545:1574 An azide-amine compound with a poly(ethylene glycol) linker was evaluated for use in histochemical staining. 37126482 9 74 theme cancer 1651:1656 arg1 tissues 1658:1664 Formalin-fixed pancreatic cancer tissues 1625:1664 Formalin-fixed pancreatic cancer tissues 1625:1664 Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. 37126482 3 75 theme azide 783:787 arg1 groups 789:794 bioorthogonal click chemistry alkyne or azide groups 743:794 groups 789:794 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 2 76 theme high-performance 548:563 arg1 chromatography 572:585 high-performance liquid chromatography 548:585 high-performance liquid chromatography 548:585 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 7 77 theme acid 1500:1503 arg1 N-glycans 1505:1513 alkyne-modified α2,3-linked sialic acid N-glycans 1465:1513 alkyne-modified α2,3-linked sialic acid N-glycans 1465:1513 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 3 78 theme sialic 823:828 arg1 acids 830:834 α2,3- and α2,8-linked sialic acids 801:834 α2,3- and α2,8-linked sialic acids 801:834 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 10 79 theme new 1960:1962 arg1 tool 1973:1976 a new glycomic tool 1958:1976 a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment 1958:2062 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 37126482 7 80 theme α2,3-linked 1481:1491 arg1 acid 1500:1503 α2,3-linked sialic acid 1481:1503 alkyne-modified α2,3-linked sialic acid N-glycans 1465:1513 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 3 81 link α2,8-linked 811:821 arg1 acids 830:834 α2,3- and α2,8-linked sialic acids 801:834 α2,3- and α2,8-linked sialic acids 801:834 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 8 82 with compound 1531:1538 arg1 linker 1569:1574 a poly(ethylene glycol) linker 1545:1574 a poly(ethylene glycol) linker 1545:1574 An azide-amine compound with a poly(ethylene glycol) linker was evaluated for use in histochemical staining. 37126482 5 83 theme sialic 1123:1128 arg1 glycoproteins 1135:1147 α2,3-linked sialic acid glycoproteins 1111:1147 α2,3-linked sialic acid glycoproteins 1111:1147 Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. 37126482 4 84 theme protein 966:972 arg1 carriers 974:981 model protein carriers 960:981 model protein carriers 960:981 These chemical modifications were validated and structurally characterized using model isomeric sialic acid conjugates and model protein carriers. 37126482 6 85 theme isomers 1268:1274 arg1 detection 1209:1217 detection 1209:1217 detection 1209:1217 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 6 85 theme isomers 1268:1274 arg1 visualization 1223:1235 visualization 1223:1235 visualization 1223:1235 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 4 86 theme acid 940:943 arg1 conjugates 945:954 model isomeric sialic acid conjugates 918:954 model isomeric sialic acid conjugates 918:954 These chemical modifications were validated and structurally characterized using model isomeric sialic acid conjugates and model protein carriers. 37126482 0 87 theme N-Glycan 73:80 arg1 Spectrometry 101:112 N-Glycan MALDI Imaging Mass Spectrometry 73:112 N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids 73:145 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 2 88 theme isomers 503:509 arg1 analysis 479:486 the analysis 475:486 the analysis of sialic acid isomers and their glycoconjugate carriers 475:543 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 6 89 theme sialic 1256:1261 arg1 isomers 1268:1274 N-linked glycan sialic acid isomers 1240:1274 N-linked glycan sialic acid isomers 1240:1274 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 6 90 link N-linked 1240:1247 arg1 isomers 1268:1274 N-linked glycan sialic acid isomers 1240:1274 N-linked glycan sialic acid isomers 1240:1274 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 0 91 theme Imaging 88:94 arg1 Spectrometry 101:112 N-Glycan MALDI Imaging Mass Spectrometry 73:112 N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids 73:145 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 1 92 theme Sialic 148:153 arg1 isomers 160:166 Sialic acid isomers 148:166 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini 148:224 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 2 93 theme sialic 491:496 arg1 isomers 503:509 sialic acid isomers 491:509 sialic acid isomers 491:509 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 1 94 theme mass 329:332 arg1 differences 334:344 mass differences 329:344 mass differences in traditional mass spectrometry experiments 329:389 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 2 95 theme carriers 536:543 arg1 analysis 479:486 the analysis 475:486 the analysis of sialic acid isomers and their glycoconjugate carriers 475:543 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 7 96 used used 1412:1415 arg2 tissues 1366:1372 Formalin-fixed paraffin-embedded prostate cancer tissues 1317:1372 Formalin-fixed paraffin-embedded prostate cancer tissues 1317:1372 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 7 96 used used 1412:1415 arg2 lines 1401:1405 pancreatic cancer cell lines 1378:1405 pancreatic cancer cell lines 1378:1405 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 0 97 theme Tissues 117:123 arg1 Spectrometry 101:112 N-Glycan MALDI Imaging Mass Spectrometry 73:112 N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids 73:145 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 5 98 theme second 1031:1036 arg1 reagent 1048:1054 the second amidation reagent 1027:1054 the second amidation reagent 1027:1054 Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. 37126482 0 99 theme Chemical 14:21 arg1 Probes 32:37 Bioorthogonal Chemical Labeling Probes 0:37 Bioorthogonal Chemical Labeling Probes 0:37 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 1 100 theme mass 361:364 arg1 spectrometry 366:377 traditional mass spectrometry 349:377 traditional mass spectrometry experiments 349:389 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 5 101 theme alkyne-amine 994:1005 arg1 Use 984:986 Use 984:986 Use of an alkyne-amine, propargylamine, as the second amidation reagent 984:1054 Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. 37126482 1 102 from differences 334:344 arg1 experiments 379:389 traditional mass spectrometry experiments 349:389 traditional mass spectrometry experiments 349:389 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 1 103 dep α2,3 187:190 arg1 linkage 200:206 linkage 200:206 linkage 200:206 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 3 104 theme derivatization 671:684 arg1 schemes 686:692 novel derivatization schemes 665:692 novel derivatization schemes 665:692 Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. 37126482 8 105 theme poly 1547:1550 arg1 linker 1569:1574 a poly(ethylene glycol) linker 1545:1574 a poly(ethylene glycol) linker 1545:1574 An azide-amine compound with a poly(ethylene glycol) linker was evaluated for use in histochemical staining. 37126482 0 106 theme Sialic 49:54 arg1 Isomers 61:67 Sialic Acid Isomers 49:67 Sialic Acid Isomers 49:67 Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. 37126482 5 107 theme alkyne 1082:1087 arg1 group 1100:1104 an alkyne functional group 1079:1104 an alkyne functional group into α2,3-linked sialic acid glycoproteins 1079:1147 Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. 37126482 7 108 theme cancer 1389:1394 arg1 lines 1401:1405 pancreatic cancer cell lines 1378:1405 pancreatic cancer cell lines 1378:1405 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 7 109 link α2,3-linked 1481:1491 arg1 acid 1500:1503 α2,3-linked sialic acid 1481:1503 alkyne-modified α2,3-linked sialic acid N-glycans 1465:1513 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 2 110 theme derivatization 401:414 arg1 strategies 416:425 Multiple derivatization strategies 392:425 Multiple derivatization strategies 392:425 Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. 37126482 10 111 theme chemical 1831:1838 arg1 introduction 1840:1851 The direct chemical introduction 1820:1851 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins 1820:1947 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 37126482 9 112 theme copper 1733:1738 arg1 catalyst 1740:1747 copper catalyst 1733:1747 copper catalyst 1733:1747 Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. 37126482 6 113 theme spectrometry 1292:1303 arg1 approaches 1305:1314 mass spectrometry approaches 1287:1314 mass spectrometry approaches 1287:1314 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 7 114 theme cancer 1359:1364 arg1 tissues 1366:1372 Formalin-fixed paraffin-embedded prostate cancer tissues 1317:1372 Formalin-fixed paraffin-embedded prostate cancer tissues 1317:1372 Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. 37126482 1 115 theme glycan 211:216 arg1 termini 218:224 glycan termini 211:224 glycan termini 211:224 Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. 37126482 6 116 theme cultured 1173:1180 arg1 cells 1182:1186 cultured cells 1173:1186 cultured cells 1173:1186 In tissues, serum, and cultured cells, this allows for the detection and visualization of N-linked glycan sialic acid isomers by imaging mass spectrometry approaches. 37126482 10 117 theme click 1870:1874 arg1 reagents 1886:1893 bioorthogonal click chemistry reagents 1856:1893 bioorthogonal click chemistry reagents 1856:1893 The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment. 36709920 6 0 theme disease 883:889 arg1 pathobiology 855:866 the pathobiology 851:866 the pathobiology of the cardiac disease observed in PGM1-CDG 851:910 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 12 1 theme gene 2050:2053 arg1 therapy 2067:2073 AAV9-PGM1 gene replacement therapy 2040:2073 AAV9-PGM1 gene replacement therapy 2040:2073 Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. 36709920 11 2 from alterations 1870:1880 arg1 proteins 1897:1904 sarcolemmal proteins 1885:1904 sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses 1885:1992 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 11 2 from alterations 1870:1880 arg1 subunits 1926:1933 different subunits 1916:1933 different subunits of laminin-211, which was confirmed by immunoblot analyses 1916:1992 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 11 3 theme immunoblot 1974:1983 arg1 analyses 1985:1992 immunoblot analyses 1974:1992 immunoblot analyses 1974:1992 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 3 4 theme liver 533:537 arg1 disease 539:545 liver disease 533:545 liver disease 533:545 Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy. 36709920 8 5 from pathology 1437:1445 arg1 explant 1462:1468 the cardiac explant 1450:1468 the cardiac explant of an individual with PGM1-CDG 1450:1499 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 0 6 theme AAV-based 0:8 arg1 therapy 15:21 AAV-based gene therapy 0:21 AAV-based gene therapy 0:21 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 12 7 theme KO 2028:2029 arg1 mice 2031:2034 KO mice 2028:2034 KO mice 2028:2034 Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. 36709920 10 8 theme mutant 1621:1626 arg1 mice 1628:1631 mutant mice 1621:1631 mutant mice 1621:1631 Transcriptomic analysis of hearts from mutant mice demonstrated a gene signature of DCM. 36709920 11 9 theme glycosylation 1831:1843 arg1 changes 1845:1851 broad glycosylation changes 1825:1851 broad glycosylation changes 1825:1851 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 1 10 from humans 259:264 arg1 Disorders 223:231 the third most common N-linked Congenital Disorders 181:231 the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans 181:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 10 from humans 259:264 arg1 deficiency 153:162 PGM1 deficiency 148:162 PGM1 deficiency 148:162 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 11 link N-linked 203:210 arg1 Disorders 223:231 the third most common N-linked Congenital Disorders 181:231 the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans 181:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 11 link N-linked 203:210 arg1 deficiency 153:162 PGM1 deficiency 148:162 PGM1 deficiency 148:162 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 6 12 theme novel 930:934 arg1 model 1038:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 8 13 theme excess 1260:1265 arg1 accumulation 1276:1287 excess glycogen accumulation 1260:1287 excess glycogen accumulation 1260:1287 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 10 14 theme hearts 1609:1614 arg1 analysis 1597:1604 Transcriptomic analysis 1582:1604 Transcriptomic analysis of hearts from mutant mice 1582:1631 Transcriptomic analysis of hearts from mutant mice demonstrated a gene signature of DCM. 36709920 0 15 theme phosphoglucomutase 104:121 arg1 deficiency 125:134 phosphoglucomutase I deficiency 104:134 phosphoglucomutase I deficiency (PGM1-CDG) 104:145 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 0 15 theme phosphoglucomutase 104:121 arg1 PGM1-CDG 137:144 PGM1-CDG 137:144 PGM1-CDG 137:144 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 1 16 theme third 185:189 arg1 Disorders 223:231 the third most common N-linked Congenital Disorders 181:231 the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans 181:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 16 theme third 185:189 arg1 deficiency 153:162 PGM1 deficiency 148:162 PGM1 deficiency 148:162 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 12 17 theme phenotype 2123:2131 arg1 progression 2100:2110 the progression 2096:2110 the progression of the DCM phenotype 2096:2131 Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. 36709920 10 18 theme gene 1648:1651 arg1 signature 1653:1661 a gene signature 1646:1661 a gene signature of DCM 1646:1668 Transcriptomic analysis of hearts from mutant mice demonstrated a gene signature of DCM. 36709920 0 19 theme deficiency 125:134 arg1 model 95:99 a mouse model 87:99 a mouse model of phosphoglucomutase I deficiency (PGM1-CDG) 87:145 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 1 20 theme common 196:201 arg1 Disorders 223:231 the third most common N-linked Congenital Disorders 181:231 the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans 181:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 20 theme common 196:201 arg1 deficiency 153:162 PGM1 deficiency 148:162 PGM1 deficiency 148:162 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 12 21 theme PGM1 2020:2023 arg1 augmentation 2004:2015 augmentation 2004:2015 augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy 2004:2073 Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. 36709920 8 22 theme individual 1476:1485 arg1 explant 1462:1468 the cardiac explant 1450:1468 the cardiac explant of an individual with PGM1-CDG 1450:1499 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 4 23 theme ejection 701:708 arg1 LVEF 720:723 LVEF 720:723 LVEF 720:723 Here we report on left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG. 36709920 4 23 theme ejection 701:708 arg1 fraction 710:717 left ventricular ejection fraction 684:717 left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG 684:755 Here we report on left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG. 36709920 12 24 theme DCM 2119:2121 arg1 phenotype 2123:2131 the DCM phenotype 2115:2131 the DCM phenotype 2115:2131 Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. 36709920 11 25 theme mutant 1777:1782 arg1 mice 1784:1787 mutant mice 1777:1787 mutant mice 1777:1787 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 10 26 from mice 1628:1631 arg1 hearts 1609:1614 hearts 1609:1614 hearts from mutant mice 1609:1631 Transcriptomic analysis of hearts from mutant mice demonstrated a gene signature of DCM. 36709920 10 26 from mice 1628:1631 arg1 analysis 1597:1604 Transcriptomic analysis 1582:1604 Transcriptomic analysis of hearts from mutant mice 1582:1631 Transcriptomic analysis of hearts from mutant mice demonstrated a gene signature of DCM. 36709920 9 27 theme decreased 1524:1532 arg1 function 1548:1555 decreased mitochondrial function 1524:1555 decreased mitochondrial function 1524:1555 In addition, we found decreased mitochondrial function in the heart of KO mice. 36709920 11 28 from expression 1736:1745 arg1 tissue 1767:1772 left ventricular tissue 1750:1772 left ventricular tissue of mutant mice 1750:1787 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 7 29 with individuals 1199:1209 arg1 PGM1-CDG 1216:1223 PGM1-CDG 1216:1223 PGM1-CDG 1216:1223 Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. 36709920 11 30 theme sarcolemmal 1885:1895 arg1 proteins 1897:1904 sarcolemmal proteins 1885:1904 sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses 1885:1992 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 11 30 theme sarcolemmal 1885:1895 arg1 subunits 1926:1933 different subunits 1916:1933 different subunits of laminin-211, which was confirmed by immunoblot analyses 1916:1992 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 6 31 theme mouse 982:986 arg1 ortholog 988:995 mouse ortholog 982:995 mouse ortholog of human PGM1 982:1009 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 4 32 theme left 684:687 arg1 LVEF 720:723 LVEF 720:723 LVEF 720:723 Here we report on left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG. 36709920 4 32 theme left 684:687 arg1 fraction 710:717 left ventricular ejection fraction 684:717 left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG 684:755 Here we report on left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG. 36709920 11 33 theme glycoproteomic 1792:1805 arg1 analysis 1807:1814 a glycoproteomic analysis 1790:1814 a glycoproteomic analysis 1790:1814 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 0 34 theme cardiomyopathy 69:82 arg1 progression 46:56 the progression 42:56 the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG) 42:145 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 1 35 theme PGM1 148:151 arg1 Disorders 223:231 the third most common N-linked Congenital Disorders 181:231 the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans 181:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 35 theme PGM1 148:151 arg1 deficiency 153:162 PGM1 deficiency 148:162 PGM1 deficiency 148:162 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 6 36 theme gene 976:979 arg1 model 1038:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 11 37 from changes 1710:1716 arg1 expression 1736:1745 global protein expression 1721:1745 global protein expression in left ventricular tissue of mutant mice 1721:1787 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 6 38 theme conditional 959:969 arg1 model 1038:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 11 39 theme broad 1825:1829 arg1 changes 1845:1851 broad glycosylation changes 1825:1851 broad glycosylation changes 1825:1851 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 7 40 theme similar 1174:1180 arg1 phenotype 1089:1097 a DCM phenotype 1083:1097 a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG 1083:1223 Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. 36709920 9 41 theme mice 1576:1579 arg1 heart 1564:1568 the heart 1560:1568 the heart of KO mice 1560:1579 In addition, we found decreased mitochondrial function in the heart of KO mice. 36709920 10 42 theme DCM 1666:1668 arg1 signature 1653:1661 a gene signature 1646:1661 a gene signature of DCM 1646:1668 Transcriptomic analysis of hearts from mutant mice demonstrated a gene signature of DCM. 36709920 7 43 theme ventricular 1153:1163 arg1 dilation 1165:1172 left ventricular dilation 1148:1172 left ventricular dilation 1148:1172 Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. 36709920 6 44 theme Pgm2 1022:1025 arg1 model 1038:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 2 45 theme early 417:421 arg1 onset 423:427 the early onset 413:427 the early onset of dilated cardiomyopathy (DCM) 413:459 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 2 45 theme early 417:421 arg1 complication 397:408 the most life-threatening complication 371:408 the most life-threatening complication 371:408 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 2 46 theme coagulation 340:350 arg1 symptoms 352:359 liver, musculoskeletal, endocrine, and coagulation symptoms 301:359 liver, musculoskeletal, endocrine, and coagulation symptoms 301:359 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 6 47 theme knockout 1012:1019 arg1 model 1038:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 11 48 theme protein 1728:1734 arg1 expression 1736:1745 global protein expression 1721:1745 global protein expression in left ventricular tissue of mutant mice 1721:1787 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 2 49 theme life-threatening 380:395 arg1 onset 423:427 the early onset 413:427 the early onset of dilated cardiomyopathy (DCM) 413:459 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 2 49 theme life-threatening 380:395 arg1 complication 397:408 the most life-threatening complication 371:408 the most life-threatening complication 371:408 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 7 50 theme ejection 1126:1133 arg1 fraction 1135:1142 significantly reduced ejection fraction 1104:1142 significantly reduced ejection fraction 1104:1142 Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. 36709920 6 51 theme PGM1 1006:1009 arg1 ortholog 988:995 mouse ortholog 982:995 mouse ortholog of human PGM1 982:1009 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 2 52 theme cardiomyopathy 440:453 arg1 onset 423:427 the early onset 413:427 the early onset of dilated cardiomyopathy (DCM) 413:459 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 2 52 theme cardiomyopathy 440:453 arg1 complication 397:408 the most life-threatening complication 371:408 the most life-threatening complication 371:408 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 2 53 theme endocrine 325:333 arg1 symptoms 352:359 liver, musculoskeletal, endocrine, and coagulation symptoms 301:359 liver, musculoskeletal, endocrine, and coagulation symptoms 301:359 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 12 54 from PGM1 2020:2023 arg1 mice 2031:2034 KO mice 2028:2034 KO mice 2028:2034 Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. 36709920 11 55 theme ventricular 1755:1765 arg1 tissue 1767:1772 left ventricular tissue 1750:1772 left ventricular tissue of mutant mice 1750:1787 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 2 56 theme musculoskeletal 308:322 arg1 symptoms 352:359 liver, musculoskeletal, endocrine, and coagulation symptoms 301:359 liver, musculoskeletal, endocrine, and coagulation symptoms 301:359 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 4 57 from fraction 710:717 arg1 individuals 731:741 6 individuals 729:741 6 individuals with PGM1-CDG 729:755 Here we report on left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG. 36709920 1 58 theme N-linked 203:210 arg1 Disorders 223:231 the third most common N-linked Congenital Disorders 181:231 the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans 181:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 58 theme N-linked 203:210 arg1 deficiency 153:162 PGM1 deficiency 148:162 PGM1 deficiency 148:162 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 12 59 from augmentation 2004:2015 arg1 mice 2031:2034 KO mice 2028:2034 KO mice 2028:2034 Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. 36709920 11 60 theme laminin-211 1938:1948 arg1 subunits 1926:1933 different subunits 1916:1933 different subunits of laminin-211, which was confirmed by immunoblot analyses 1916:1992 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 7 61 theme DCM 1085:1087 arg1 phenotype 1089:1097 a DCM phenotype 1083:1097 a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG 1083:1223 Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. 36709920 1 62 theme Glycosylation 236:248 arg1 Disorders 223:231 the third most common N-linked Congenital Disorders 181:231 the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans 181:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 62 theme Glycosylation 236:248 arg1 deficiency 153:162 PGM1 deficiency 148:162 PGM1 deficiency 148:162 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 6 63 theme cardiac 875:881 arg1 disease 883:889 the cardiac disease 871:889 the cardiac disease observed in PGM1-CDG 871:910 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 7 64 with phenotype 1089:1097 arg1 dilation 1165:1172 left ventricular dilation 1148:1172 left ventricular dilation 1148:1172 Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. 36709920 7 64 with phenotype 1089:1097 arg1 fraction 1135:1142 significantly reduced ejection fraction 1104:1142 significantly reduced ejection fraction 1104:1142 Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. 36709920 2 65 theme Affected 267:274 arg1 individuals 276:286 Affected individuals 267:286 Affected individuals 267:286 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 12 66 theme AAV9-PGM1 2040:2048 arg1 therapy 2067:2073 AAV9-PGM1 gene replacement therapy 2040:2073 AAV9-PGM1 gene replacement therapy 2040:2073 Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. 36709920 8 67 theme Z-disk 1343:1348 arg1 disarray 1350:1357 Z-disk disarray 1343:1357 Z-disk disarray 1343:1357 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 10 68 theme Transcriptomic 1582:1595 arg1 analysis 1597:1604 Transcriptomic analysis 1582:1604 Transcriptomic analysis of hearts from mutant mice 1582:1631 Transcriptomic analysis of hearts from mutant mice demonstrated a gene signature of DCM. 36709920 11 69 theme mild 1705:1708 arg1 changes 1710:1716 only mild changes 1700:1716 only mild changes in global protein expression in left ventricular tissue of mutant mice 1700:1787 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 7 70 theme Echocardiography 1045:1060 arg1 studies 1062:1068 Echocardiography studies 1045:1068 Echocardiography studies 1045:1068 Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. 36709920 3 71 theme D-galactose 496:506 arg1 supplementation 508:522 oral D-galactose supplementation 491:522 oral D-galactose supplementation 491:522 Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy. 36709920 12 72 theme replacement 2055:2065 arg1 therapy 2067:2073 AAV9-PGM1 gene replacement therapy 2040:2073 AAV9-PGM1 gene replacement therapy 2040:2073 Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. 36709920 2 73 theme liver 301:305 arg1 symptoms 352:359 liver, musculoskeletal, endocrine, and coagulation symptoms 301:359 liver, musculoskeletal, endocrine, and coagulation symptoms 301:359 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 6 74 theme cardiomyocyte-specific 936:957 arg1 model 1038:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 8 75 theme Histological 1226:1237 arg1 studies 1239:1245 Histological studies 1226:1245 Histological studies 1226:1245 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 0 76 theme I 123:123 arg1 deficiency 125:134 phosphoglucomutase I deficiency 104:134 phosphoglucomutase I deficiency (PGM1-CDG) 104:145 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 0 76 theme I 123:123 arg1 PGM1-CDG 137:144 PGM1-CDG 137:144 PGM1-CDG 137:144 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 6 77 located observed 891:898 arg2 disease 883:889 the cardiac disease 871:889 the cardiac disease observed in PGM1-CDG 871:910 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 6 77 located observed 891:898 arg1 PGM1-CDG 903:910 PGM1-CDG 903:910 PGM1-CDG 903:910 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 4 78 with individuals 731:741 arg1 PGM1-CDG 748:755 PGM1-CDG 748:755 PGM1-CDG 748:755 Here we report on left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG. 36709920 1 79 from Glycosylation 236:248 arg1 humans 259:264 humans 259:264 humans 259:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 80 theme most 191:194 arg1 Disorders 223:231 the third most common N-linked Congenital Disorders 181:231 the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans 181:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 80 theme most 191:194 arg1 deficiency 153:162 PGM1 deficiency 148:162 PGM1 deficiency 148:162 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 8 81 theme glycogen 1267:1274 arg1 accumulation 1276:1287 excess glycogen accumulation 1260:1287 excess glycogen accumulation 1260:1287 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 1 82 from Disorders 223:231 arg1 humans 259:264 humans 259:264 humans 259:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 3 83 theme coagulation 562:572 arg1 abnormalities 574:586 coagulation abnormalities 562:586 coagulation abnormalities 562:586 Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy. 36709920 4 84 theme ventricular 689:699 arg1 LVEF 720:723 LVEF 720:723 LVEF 720:723 Here we report on left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG. 36709920 4 84 theme ventricular 689:699 arg1 fraction 710:717 left ventricular ejection fraction 684:717 left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG 684:755 Here we report on left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG. 36709920 11 85 theme significant 1858:1868 arg1 alterations 1870:1880 significant alterations 1858:1880 significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses 1858:1992 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 6 86 theme human 1000:1004 arg1 PGM1 1006:1009 human PGM1 1000:1009 human PGM1 1000:1009 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 11 87 theme mice 1784:1787 arg1 tissue 1767:1772 left ventricular tissue 1750:1772 left ventricular tissue of mutant mice 1750:1787 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 0 88 theme dilated 61:67 arg1 cardiomyopathy 69:82 dilated cardiomyopathy 61:82 dilated cardiomyopathy 61:82 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 9 89 theme mitochondrial 1534:1546 arg1 function 1548:1555 decreased mitochondrial function 1524:1555 decreased mitochondrial function 1524:1555 In addition, we found decreased mitochondrial function in the heart of KO mice. 36709920 8 90 theme ultrastructural 1309:1323 arg1 analysis 1325:1332 ultrastructural analysis 1309:1332 ultrastructural analysis 1309:1332 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 5 91 from low 782:784 arg1 most 789:792 most 789:792 most 789:792 LVEF was pathologically low in most of these individuals and varied between 10-65%. 36709920 5 91 from low 782:784 arg1 individuals 803:813 these individuals 797:813 these individuals 797:813 LVEF was pathologically low in most of these individuals and varied between 10-65%. 36709920 0 92 theme mouse 89:93 arg1 model 95:99 a mouse model 87:99 a mouse model of phosphoglucomutase I deficiency (PGM1-CDG) 87:145 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 6 93 theme Pgm2 971:974 arg1 model 1038:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 0 94 from progression 46:56 arg1 model 95:99 a mouse model 87:99 a mouse model of phosphoglucomutase I deficiency (PGM1-CDG) 87:145 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 9 95 theme KO 1573:1574 arg1 mice 1576:1579 KO mice 1573:1579 KO mice 1573:1579 In addition, we found decreased mitochondrial function in the heart of KO mice. 36709920 6 96 theme mouse 1032:1036 arg1 model 1038:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 8 97 theme swollen/fragmented 1363:1380 arg1 mitochondria 1382:1393 swollen/fragmented mitochondria 1363:1393 swollen/fragmented mitochondria 1363:1393 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 0 98 theme gene 10:13 arg1 therapy 15:21 AAV-based gene therapy 0:21 AAV-based gene therapy 0:21 AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). 36709920 5 99 from most 789:792 arg1 low 782:784 low 782:784 low 782:784 LVEF was pathologically low in most of these individuals and varied between 10-65%. 36709920 6 100 theme cKO 1027:1029 arg1 model 1038:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model 928:1042 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 11 101 theme global 1721:1726 arg1 expression 1736:1745 global protein expression 1721:1745 global protein expression in left ventricular tissue of mutant mice 1721:1787 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 7 102 theme reduced 1118:1124 arg1 fraction 1135:1142 significantly reduced ejection fraction 1104:1142 significantly reduced ejection fraction 1104:1142 Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. 36709920 12 103 from mice 2031:2034 arg1 augmentation 2004:2015 augmentation 2004:2015 augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy 2004:2073 Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. 36709920 3 104 theme fatal 616:620 arg1 cardiomyopathy 622:635 the fatal cardiomyopathy 612:635 the fatal cardiomyopathy 612:635 Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy. 36709920 6 105 dep model 1038:1042 arg1 ortholog 988:995 mouse ortholog 982:995 mouse ortholog of human PGM1 982:1009 To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. 36709920 2 106 theme most 375:378 arg1 onset 423:427 the early onset 413:427 the early onset of dilated cardiomyopathy (DCM) 413:459 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 2 106 theme most 375:378 arg1 complication 397:408 the most life-threatening complication 371:408 the most life-threatening complication 371:408 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 2 107 theme dilated 432:438 arg1 cardiomyopathy 440:453 dilated cardiomyopathy 432:453 dilated cardiomyopathy (DCM) 432:459 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 2 107 theme dilated 432:438 arg1 DCM 456:458 DCM 456:458 DCM 456:458 Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). 36709920 11 108 theme left 1750:1753 arg1 tissue 1767:1772 left ventricular tissue 1750:1772 left ventricular tissue of mutant mice 1750:1787 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 8 109 theme ultrastructural 1421:1435 arg1 pathology 1437:1445 the ultrastructural pathology 1417:1445 the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG 1417:1499 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 8 110 with individual 1476:1485 arg1 PGM1-CDG 1492:1499 PGM1-CDG 1492:1499 PGM1-CDG 1492:1499 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 11 111 theme different 1916:1924 arg1 subunits 1926:1933 different subunits 1916:1933 different subunits of laminin-211, which was confirmed by immunoblot analyses 1916:1992 Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. 36709920 3 112 theme associated 645:654 arg1 myopathy 656:663 the associated myopathy 641:663 the associated myopathy 641:663 Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy. 36709920 3 113 theme oral 491:494 arg1 supplementation 508:522 oral D-galactose supplementation 491:522 oral D-galactose supplementation 491:522 Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy. 36709920 1 114 theme Congenital 212:221 arg1 Disorders 223:231 the third most common N-linked Congenital Disorders 181:231 the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans 181:264 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 1 114 theme Congenital 212:221 arg1 deficiency 153:162 PGM1 deficiency 148:162 PGM1 deficiency 148:162 PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. 36709920 10 115 from analysis 1597:1604 arg1 mice 1628:1631 mutant mice 1621:1631 mutant mice 1621:1631 Transcriptomic analysis of hearts from mutant mice demonstrated a gene signature of DCM. 36709920 8 116 theme cardiac 1454:1460 arg1 explant 1462:1468 the cardiac explant 1450:1468 the cardiac explant of an individual with PGM1-CDG 1450:1499 Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. 36709920 7 117 theme left 1148:1151 arg1 dilation 1165:1172 left ventricular dilation 1148:1172 left ventricular dilation 1148:1172 Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. 35343792 19 0 theme neural 2682:2687 arg1 tropism 2689:2695 arenavirus neural tropism 2671:2695 arenavirus neural tropism 2671:2695 Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism. 35343792 18 1 from study 2460:2464 arg1 finding 2442:2448 Another important finding 2424:2448 Another important finding from this study 2424:2464 Another important finding from this study is that the F438I substitution in GPC TMD could substantially affect MACV replication in neurons. 35343792 0 2 theme Fever 172:176 arg1 Models 141:146 Animal Models 134:146 Animal Models of Bolivian Hemorrhagic Fever 134:176 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 3 3 theme sites 519:523 arg1 disruption 480:489 the disruption 476:489 the disruption of specific N-linked glycan sites on the glycoprotein (GPC) 476:549 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 15 4 theme GPC 2186:2188 arg1 TMD 2190:2192 the GPC TMD 2182:2192 the GPC TMD 2182:2192 Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC and also introduced the corresponding F438I substitution in the GPC TMD. 35343792 6 5 theme transmembrane 868:880 arg1 domain 882:887 the GPC transmembrane domain 860:887 the GPC transmembrane domain (TMD) 860:893 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 6 5 theme transmembrane 868:880 arg1 TMD 890:892 TMD 890:892 TMD 890:892 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 6 6 from substitution 844:855 arg1 domain 882:887 the GPC transmembrane domain 860:887 the GPC transmembrane domain (TMD) 860:893 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 6 6 from substitution 844:855 arg1 TMD 890:892 TMD 890:892 TMD 890:892 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 3 7 theme glycan 512:517 arg1 sites 519:523 specific N-linked glycan sites 494:523 specific N-linked glycan sites on the glycoprotein (GPC) 494:549 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 8 8 theme -γ 1189:1190 arg1 mice 1197:1200 IFN-α/β and -γ R-/- mice 1177:1200 IFN-α/β and -γ R-/- mice 1177:1200 The MACV mutant is fully attenuated in IFN-α/β and -γ R-/- mice and outbred guinea pigs. 35343792 3 9 from disruption 480:489 arg1 GPC 546:548 GPC 546:548 GPC 546:548 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 3 9 from disruption 480:489 arg1 glycoprotein 532:543 the glycoprotein 528:543 the glycoprotein (GPC) 528:549 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 15 10 theme reverse 2050:2056 arg1 genetics 2058:2065 reverse genetics 2050:2065 reverse genetics 2050:2065 Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC and also introduced the corresponding F438I substitution in the GPC TMD. 35343792 8 11 theme MACV 1142:1145 arg1 mutant 1147:1152 The MACV mutant 1138:1152 The MACV mutant 1138:1152 The MACV mutant is fully attenuated in IFN-α/β and -γ R-/- mice and outbred guinea pigs. 35343792 18 12 theme important 2432:2440 arg1 finding 2442:2448 Another important finding 2424:2448 Another important finding from this study 2424:2464 Another important finding from this study is that the F438I substitution in GPC TMD could substantially affect MACV replication in neurons. 35343792 19 13 theme mutation 2659:2666 arg1 implication 2639:2649 the implication 2635:2649 the implication of this mutation in arenavirus neural tropism 2635:2695 Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism. 35343792 19 13 theme mutation 2659:2666 arg1 mechanism 2621:2629 the underlying mechanism 2606:2629 the underlying mechanism 2606:2629 Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism. 35343792 11 14 from GPC 1546:1548 arg1 virulence 1564:1572 arenavirus virulence 1553:1572 arenavirus virulence 1553:1572 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 6 15 theme lethal 925:930 arg1 model 938:942 a lethal mouse model 923:942 a lethal mouse model 923:942 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 8 16 theme outbred 1206:1212 arg1 pigs 1221:1224 outbred guinea pigs 1206:1224 outbred guinea pigs 1206:1224 The MACV mutant is fully attenuated in IFN-α/β and -γ R-/- mice and outbred guinea pigs. 35343792 14 17 theme JUNV 2038:2041 arg1 attenuation 2023:2033 full and stable attenuation 2007:2033 full and stable attenuation of JUNV 2007:2041 Nevertheless, mutating either of them is not sufficient for full and stable attenuation of JUNV. 35343792 19 18 theme arenavirus 2671:2680 arg1 tropism 2689:2695 arenavirus neural tropism 2671:2695 arenavirus neural tropism 2671:2695 Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism. 35343792 17 19 theme rational 2344:2351 arg1 attenuation 2353:2363 rational attenuation 2344:2363 rational attenuation of highly pathogenic arenaviruses for vaccine development 2344:2421 Thus, our studies highlight the feasibility of rational attenuation of highly pathogenic arenaviruses for vaccine development. 35343792 18 20 from substitution 2484:2495 arg1 TMD 2504:2506 GPC TMD 2500:2506 GPC TMD 2500:2506 Another important finding from this study is that the F438I substitution in GPC TMD could substantially affect MACV replication in neurons. 35343792 1 21 theme severe 228:233 arg1 disease 262:268 severe hemorrhagic and neurologic disease 228:268 severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable 228:339 Several highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable. 35343792 8 22 theme IFN-α/β 1177:1183 arg1 mice 1197:1200 IFN-α/β and -γ R-/- mice 1177:1200 IFN-α/β and -γ R-/- mice 1177:1200 The MACV mutant is fully attenuated in IFN-α/β and -γ R-/- mice and outbred guinea pigs. 35343792 1 23 from disease 262:268 arg1 humans 273:278 humans 273:278 humans 273:278 Several highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable. 35343792 3 24 theme interferon 583:592 arg1 alpha/beta 594:603 interferon alpha/beta 583:603 interferon alpha/beta 583:603 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 13 25 from glycans 1859:1865 arg1 TMD 1906:1908 the GPC TMD 1898:1908 the GPC TMD 1898:1908 We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. 35343792 13 25 from glycans 1859:1865 arg1 GPC 1870:1872 GPC 1870:1872 GPC 1870:1872 We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. 35343792 15 26 gly glycosylation 2090:2102 arg2 sites 2104:2108 specific glycosylation sites 2081:2108 specific glycosylation sites 2081:2108 Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC and also introduced the corresponding F438I substitution in the GPC TMD. 35343792 7 27 contain containing 1033:1042 arg2 mutations 1044:1052 mutations 1044:1052 mutations 1044:1052 In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in the GPC TMD. 35343792 7 27 contain containing 1033:1042 arg1 MACV 1028:1031 a MACV 1026:1031 a MACV containing mutations at two glycosylation sites 1026:1079 In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in the GPC TMD. 35343792 0 28 theme Bolivian 151:158 arg1 Fever 172:176 Bolivian Hemorrhagic Fever 151:176 Bolivian Hemorrhagic Fever 151:176 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 15 29 theme glycosylation 2090:2102 arg1 sites 2104:2108 specific glycosylation sites 2081:2108 specific glycosylation sites 2081:2108 Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC and also introduced the corresponding F438I substitution in the GPC TMD. 35343792 15 30 theme specific 2081:2088 arg1 sites 2104:2108 specific glycosylation sites 2081:2108 specific glycosylation sites 2081:2108 Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC and also introduced the corresponding F438I substitution in the GPC TMD. 35343792 7 31 theme GPC 1129:1131 arg1 TMD 1133:1135 the GPC TMD 1125:1135 the GPC TMD 1125:1135 In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in the GPC TMD. 35343792 14 32 theme full 2007:2010 arg1 attenuation 2023:2033 full and stable attenuation 2007:2033 full and stable attenuation of JUNV 2007:2041 Nevertheless, mutating either of them is not sufficient for full and stable attenuation of JUNV. 35343792 9 33 with inoculation 1240:1250 arg1 MACV 1269:1272 this mutant MACV 1257:1272 this mutant MACV 1257:1272 Furthermore, inoculation with this mutant MACV completely protected guinea pigs from wild-type MACV lethal challenge. 35343792 5 34 theme pathogenic 755:764 arg1 arenavirus 799:808 another NW arenavirus 788:808 another NW arenavirus closely related to MACV 788:832 The highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. 35343792 5 34 theme pathogenic 755:764 arg1 JUNV 779:782 JUNV 779:782 JUNV 779:782 The highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. 35343792 5 34 theme pathogenic 755:764 arg1 virus 772:776 The highly pathogenic Junin virus 744:776 The highly pathogenic Junin virus (JUNV) 744:783 The highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. 35343792 6 35 theme intracranial 950:961 arg1 inoculation 963:973 intracranial inoculation 950:973 intracranial inoculation 950:973 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 10 36 theme F438I 1372:1376 arg1 growth 1413:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 12 37 from approved 1802:1809 arg1 Argentina 1814:1822 Argentina 1814:1822 Argentina 1814:1822 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 18 38 theme MACV 2535:2538 arg1 replication 2540:2550 MACV replication 2535:2550 MACV replication in neurons 2535:2561 Another important finding from this study is that the F438I substitution in GPC TMD could substantially affect MACV replication in neurons. 35343792 7 39 from MACV 1028:1031 arg1 TMD 1133:1135 the GPC TMD 1125:1135 the GPC TMD 1125:1135 In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in the GPC TMD. 35343792 9 40 theme mutant 1262:1267 arg1 MACV 1269:1272 this mutant MACV 1257:1272 this mutant MACV 1257:1272 Furthermore, inoculation with this mutant MACV completely protected guinea pigs from wild-type MACV lethal challenge. 35343792 12 41 theme approved 1802:1809 arg1 vaccine 1778:1784 the live attenuated Candid#1 vaccine 1749:1784 the live attenuated Candid#1 vaccine 1749:1784 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 41 theme approved 1802:1809 arg1 vaccine 1794:1800 a JUNV vaccine 1787:1800 a JUNV vaccine approved in Argentina 1787:1822 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 10 42 theme MACV 1408:1411 arg1 growth 1413:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 19 43 from mechanism 2621:2629 arg1 tropism 2689:2695 arenavirus neural tropism 2671:2695 arenavirus neural tropism 2671:2695 Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism. 35343792 0 44 theme Machupo 0:6 arg1 Virus 8:12 Machupo Virus 0:12 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein 0:99 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 15 45 theme corresponding 2146:2158 arg1 substitution 2166:2177 the corresponding F438I substitution 2142:2177 the corresponding F438I substitution 2142:2177 Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC and also introduced the corresponding F438I substitution in the GPC TMD. 35343792 19 46 theme Future 2564:2569 arg1 studies 2571:2577 Future studies 2564:2577 Future studies 2564:2577 Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism. 35343792 5 47 theme NW 796:797 arg1 arenavirus 799:808 another NW arenavirus 788:808 another NW arenavirus closely related to MACV 788:832 The highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. 35343792 5 47 theme NW 796:797 arg1 virus 772:776 The highly pathogenic Junin virus 744:776 The highly pathogenic Junin virus (JUNV) 744:783 The highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. 35343792 9 48 theme guinea 1295:1300 arg1 pigs 1302:1305 guinea pigs 1295:1305 guinea pigs 1295:1305 Furthermore, inoculation with this mutant MACV completely protected guinea pigs from wild-type MACV lethal challenge. 35343792 6 49 theme F427I 838:842 arg1 substitution 844:855 An F427I substitution 835:855 An F427I substitution in the GPC transmembrane domain (TMD) 835:893 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 10 50 theme cell 1432:1435 arg1 lines 1437:1441 neuronal cell lines 1423:1441 neuronal cell lines of mouse and human origins 1423:1468 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 3 51 theme knockout 641:648 arg1 model 663:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 2 52 theme Bolivian 410:417 arg1 fever 431:435 Bolivian hemorrhagic fever 410:435 Bolivian hemorrhagic fever in humans 410:445 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 12 53 theme JUNV 1789:1792 arg1 vaccine 1778:1784 the live attenuated Candid#1 vaccine 1749:1784 the live attenuated Candid#1 vaccine 1749:1784 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 53 theme JUNV 1789:1792 arg1 vaccine 1794:1800 a JUNV vaccine 1787:1800 a JUNV vaccine approved in Argentina 1787:1822 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 10 54 theme origins 1462:1468 arg1 lines 1437:1441 neuronal cell lines 1423:1441 neuronal cell lines of mouse and human origins 1423:1468 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 11 55 theme rational 1606:1613 arg1 design 1615:1620 the rational design 1602:1620 the rational design of potential vaccine candidates for highly pathogenic arenaviruses 1602:1687 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 3 56 theme specific 494:501 arg1 sites 519:523 specific N-linked glycan sites 494:523 specific N-linked glycan sites on the glycoprotein (GPC) 494:549 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 7 57 theme F438I 1103:1107 arg1 substitution 1109:1120 the corresponding F438I substitution 1085:1120 the corresponding F438I substitution in the GPC TMD 1085:1135 In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in the GPC TMD. 35343792 9 58 theme MACV 1322:1325 arg1 challenge 1334:1342 wild-type MACV lethal challenge 1312:1342 wild-type MACV lethal challenge 1312:1342 Furthermore, inoculation with this mutant MACV completely protected guinea pigs from wild-type MACV lethal challenge. 35343792 12 59 theme Candid 1769:1774 arg1 # 1775:1775 Candid#1 1769:1776 the live attenuated Candid#1 vaccine 1749:1784 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 60 theme attenuated 1758:1767 arg1 vaccine 1778:1784 the live attenuated Candid#1 vaccine 1749:1784 the live attenuated Candid#1 vaccine 1749:1784 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 60 theme attenuated 1758:1767 arg1 IMPORTANCE 1690:1699 IMPORTANCE 1690:1699 IMPORTANCE For arenaviruses, the only vaccine available 1690:1744 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 60 theme attenuated 1758:1767 arg1 vaccine 1794:1800 a JUNV vaccine 1787:1800 a JUNV vaccine approved in Argentina 1787:1822 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 17 61 theme attenuation 2353:2363 arg1 feasibility 2329:2339 the feasibility 2325:2339 the feasibility of rational attenuation of highly pathogenic arenaviruses for vaccine development 2325:2421 Thus, our studies highlight the feasibility of rational attenuation of highly pathogenic arenaviruses for vaccine development. 35343792 10 62 theme GPC 1364:1366 arg1 growth 1413:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 11 63 theme glycans 1519:1525 arg1 roles 1506:1510 the critical roles 1493:1510 the critical roles of the glycans 1493:1525 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 11 63 theme glycans 1519:1525 arg1 TMD 1535:1537 the TMD 1531:1537 the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses 1531:1687 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 2 64 theme World 346:350 arg1 MACV 387:390 MACV 387:390 MACV 387:390 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 2 64 theme World 346:350 arg1 virus 380:384 New World (NW) mammarenavirus Machupo virus 342:384 New World (NW) mammarenavirus Machupo virus (MACV) infection 342:401 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 12 65 theme only 1723:1726 arg1 vaccine 1728:1734 the only vaccine available 1719:1744 the only vaccine available 1719:1744 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 65 theme only 1723:1726 arg1 arenaviruses 1705:1716 arenaviruses 1705:1716 arenaviruses 1705:1716 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 3 66 theme R-/- 651:654 arg1 model 663:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 16 67 theme lethal 2279:2284 arg1 infection 2286:2294 lethal infection 2279:2294 lethal infection 2279:2294 This MACV mutant is fully attenuated in two animal models and protects animals from lethal infection. 35343792 2 68 theme virus 380:384 arg1 infection 393:401 New World (NW) mammarenavirus Machupo virus (MACV) infection 342:401 New World (NW) mammarenavirus Machupo virus (MACV) infection 342:401 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 1 69 theme neurologic 251:260 arg1 disease 262:268 severe hemorrhagic and neurologic disease 228:268 severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable 228:339 Several highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable. 35343792 2 70 from fever 431:435 arg1 humans 440:445 humans 440:445 humans 440:445 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 17 71 theme arenaviruses 2386:2397 arg1 attenuation 2353:2363 rational attenuation 2344:2363 rational attenuation of highly pathogenic arenaviruses for vaccine development 2344:2421 Thus, our studies highlight the feasibility of rational attenuation of highly pathogenic arenaviruses for vaccine development. 35343792 2 72 theme mammarenavirus 357:370 arg1 MACV 387:390 MACV 387:390 MACV 387:390 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 2 72 theme mammarenavirus 357:370 arg1 virus 380:384 New World (NW) mammarenavirus Machupo virus 342:384 New World (NW) mammarenavirus Machupo virus (MACV) infection 342:401 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 17 73 theme vaccine 2403:2409 arg1 development 2411:2421 vaccine development 2403:2421 vaccine development 2403:2421 Thus, our studies highlight the feasibility of rational attenuation of highly pathogenic arenaviruses for vaccine development. 35343792 11 74 theme arenavirus 1553:1562 arg1 virulence 1564:1572 arenavirus virulence 1553:1572 arenavirus virulence 1553:1572 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 7 75 theme glycosylation 1061:1073 arg1 sites 1075:1079 two glycosylation sites 1057:1079 two glycosylation sites 1057:1079 In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in the GPC TMD. 35343792 3 76 from sites 519:523 arg1 GPC 546:548 GPC 546:548 GPC 546:548 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 3 76 from sites 519:523 arg1 glycoprotein 532:543 the glycoprotein 528:543 the glycoprotein (GPC) 528:549 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 6 77 theme GPC 864:866 arg1 domain 882:887 the GPC transmembrane domain 860:887 the GPC transmembrane domain (TMD) 860:893 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 6 77 theme GPC 864:866 arg1 TMD 890:892 TMD 890:892 TMD 890:892 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 0 78 from Models 141:146 arg1 Immunogenic 119:129 Immunogenic 119:129 Immunogenic 119:129 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 18 79 theme GPC 2500:2502 arg1 TMD 2504:2506 GPC TMD 2500:2506 GPC TMD 2500:2506 Another important finding from this study is that the F438I substitution in GPC TMD could substantially affect MACV replication in neurons. 35343792 2 80 theme NW 353:354 arg1 MACV 387:390 MACV 387:390 MACV 387:390 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 2 80 theme NW 353:354 arg1 virus 380:384 New World (NW) mammarenavirus Machupo virus 342:384 New World (NW) mammarenavirus Machupo virus (MACV) infection 342:401 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 1 81 theme Several 179:185 arg1 mammarenaviruses 205:220 Several highly pathogenic mammarenaviruses 179:220 Several highly pathogenic mammarenaviruses 179:220 Several highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable. 35343792 11 82 from TMD 1535:1537 arg1 GPC 1546:1548 the GPC 1542:1548 the GPC 1542:1548 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 0 83 theme Transmembrane 36:48 arg1 Glycoprotein 88:99 the Glycoprotein 84:99 the Glycoprotein 84:99 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 0 83 theme Transmembrane 36:48 arg1 Domain 50:55 the Transmembrane Domain 32:55 the Transmembrane Domain 32:55 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 15 84 theme MACV 2113:2116 arg1 GPC 2118:2120 MACV GPC 2113:2120 MACV GPC 2113:2120 Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC and also introduced the corresponding F438I substitution in the GPC TMD. 35343792 3 85 dep alpha/beta 594:603 arg1 an 580:581 an 580:581 an 580:581 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 3 85 dep alpha/beta 594:603 arg1 IFN-α/β 616:622 IFN-α/β 616:622 IFN-α/β 616:622 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 3 85 dep alpha/beta 594:603 arg1 -γ 628:629 -γ 628:629 -γ 628:629 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 6 86 theme mouse 932:936 arg1 model 938:942 a lethal mouse model 923:942 a lethal mouse model 923:942 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 8 87 theme R-/- 1192:1195 arg1 mice 1197:1200 IFN-α/β and -γ R-/- mice 1177:1200 IFN-α/β and -γ R-/- mice 1177:1200 The MACV mutant is fully attenuated in IFN-α/β and -γ R-/- mice and outbred guinea pigs. 35343792 11 88 theme critical 1497:1504 arg1 roles 1506:1510 the critical roles 1493:1510 the critical roles of the glycans 1493:1525 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 1 89 theme pathogenic 194:203 arg1 mammarenaviruses 205:220 Several highly pathogenic mammarenaviruses 179:220 Several highly pathogenic mammarenaviruses 179:220 Several highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable. 35343792 6 90 dep rendered 895:902 arg1 attenuated 909:918 attenuated 909:918 rendered JUNV attenuated in a lethal mouse model after intracranial inoculation 895:973 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 0 91 theme Animal 134:139 arg1 Models 141:146 Animal Models 134:146 Animal Models of Bolivian Hemorrhagic Fever 134:176 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 3 92 theme alpha/beta 594:603 arg1 model 663:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 13 93 from residue 1887:1893 arg1 TMD 1906:1908 the GPC TMD 1898:1908 the GPC TMD 1898:1908 We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. 35343792 13 93 from residue 1887:1893 arg1 GPC 1870:1872 GPC 1870:1872 GPC 1870:1872 We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. 35343792 5 94 theme related 818:824 arg1 arenavirus 799:808 another NW arenavirus 788:808 another NW arenavirus closely related to MACV 788:832 The highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. 35343792 5 94 theme related 818:824 arg1 virus 772:776 The highly pathogenic Junin virus 744:776 The highly pathogenic Junin virus (JUNV) 744:783 The highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. 35343792 12 95 from Argentina 1814:1822 arg1 approved 1802:1809 approved 1802:1809 approved 1802:1809 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 6 96 dep attenuated 909:918 arg1 JUNV 904:907 JUNV 904:907 JUNV 904:907 An F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. 35343792 7 97 gly glycosylation 1061:1073 arg2 sites 1075:1079 two glycosylation sites 1057:1079 two glycosylation sites 1057:1079 In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in the GPC TMD. 35343792 7 97 gly glycosylation 1061:1073 arg2 two 1057:1059 two 1057:1059 two 1057:1059 In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in the GPC TMD. 35343792 14 98 theme stable 2016:2021 arg1 attenuation 2023:2033 full and stable attenuation 2007:2033 full and stable attenuation of JUNV 2007:2041 Nevertheless, mutating either of them is not sufficient for full and stable attenuation of JUNV. 35343792 3 99 theme mouse 657:661 arg1 model 663:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 16 100 theme animal 2239:2244 arg1 models 2246:2251 two animal models 2235:2251 two animal models 2235:2251 This MACV mutant is fully attenuated in two animal models and protects animals from lethal infection. 35343792 0 101 theme Hemorrhagic 160:170 arg1 Fever 172:176 Bolivian Hemorrhagic Fever 151:176 Bolivian Hemorrhagic Fever 151:176 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 11 102 theme vaccine 1635:1641 arg1 candidates 1643:1652 potential vaccine candidates 1625:1652 potential vaccine candidates for highly pathogenic arenaviruses 1625:1687 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 11 103 from roles 1506:1510 arg1 GPC 1546:1548 the GPC 1542:1548 the GPC 1542:1548 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 3 104 link N-linked 503:510 arg1 sites 519:523 specific N-linked glycan sites 494:523 specific N-linked glycan sites on the glycoprotein (GPC) 494:549 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 0 105 theme Glycosylation 61:73 arg1 Sites 75:79 Glycosylation Sites 61:79 Glycosylation Sites 61:79 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 0 105 theme Glycosylation 61:73 arg1 Glycoprotein 88:99 the Glycoprotein 84:99 the Glycoprotein 84:99 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 3 106 theme gamma 609:613 arg1 model 663:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 0 107 from Mutations 19:27 arg1 Sites 75:79 Glycosylation Sites 61:79 Glycosylation Sites 61:79 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 0 107 from Mutations 19:27 arg1 Glycoprotein 88:99 the Glycoprotein 84:99 the Glycoprotein 84:99 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 0 107 from Mutations 19:27 arg1 Domain 50:55 the Transmembrane Domain 32:55 the Transmembrane Domain 32:55 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 3 108 from glycoprotein 532:543 arg1 disruption 480:489 the disruption 476:489 the disruption of specific N-linked glycan sites on the glycoprotein (GPC) 476:549 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 11 109 theme pathogenic 1665:1674 arg1 arenaviruses 1676:1687 highly pathogenic arenaviruses 1658:1687 highly pathogenic arenaviruses 1658:1687 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 7 110 from substitution 1109:1120 arg1 TMD 1133:1135 the GPC TMD 1125:1135 the GPC TMD 1125:1135 In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in the GPC TMD. 35343792 10 111 theme substitution 1378:1389 arg1 growth 1413:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 3 112 gly glycoprotein 532:543 arg1 GPC 546:548 GPC 546:548 GPC 546:548 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 3 112 gly glycoprotein 532:543 arg1 glycoprotein 532:543 the glycoprotein 528:543 the glycoprotein (GPC) 528:549 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 16 113 theme MACV 2200:2203 arg1 mutant 2205:2210 This MACV mutant 2195:2210 This MACV mutant 2195:2210 This MACV mutant is fully attenuated in two animal models and protects animals from lethal infection. 35343792 0 114 theme Glycoprotein 88:99 arg1 Sites 75:79 Glycosylation Sites 61:79 Glycosylation Sites 61:79 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 0 114 theme Glycoprotein 88:99 arg1 Glycoprotein 88:99 the Glycoprotein 84:99 the Glycoprotein 84:99 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 0 114 theme Glycoprotein 88:99 arg1 Domain 50:55 the Transmembrane Domain 32:55 the Transmembrane Domain 32:55 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 10 115 theme TMD 1368:1370 arg1 growth 1413:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 13 116 theme JUNV 1941:1944 arg1 virulence 1928:1936 virulence 1928:1936 virulence of JUNV 1928:1944 We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. 35343792 10 117 theme impaired 1399:1406 arg1 growth 1413:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 the GPC TMD F438I substitution greatly impaired MACV growth 1360:1418 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 4 118 theme neurological 705:716 arg1 pathology 718:726 neurological pathology 705:726 neurological pathology 705:726 However, some capability to induce neurological pathology still remained. 35343792 15 119 theme F438I 2160:2164 arg1 substitution 2166:2177 the corresponding F438I substitution 2142:2177 the corresponding F438I substitution 2142:2177 Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC and also introduced the corresponding F438I substitution in the GPC TMD. 35343792 4 120 dep capability 684:693 arg1 induce 698:703 induce 698:703 to induce neurological pathology 695:726 However, some capability to induce neurological pathology still remained. 35343792 3 121 theme receptor 632:639 arg1 model 663:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model 580:667 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 2 122 theme hemorrhagic 419:429 arg1 fever 431:435 Bolivian hemorrhagic fever 410:435 Bolivian hemorrhagic fever in humans 410:445 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 5 123 theme Junin 766:770 arg1 arenavirus 799:808 another NW arenavirus 788:808 another NW arenavirus closely related to MACV 788:832 The highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. 35343792 5 123 theme Junin 766:770 arg1 JUNV 779:782 JUNV 779:782 JUNV 779:782 The highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. 35343792 5 123 theme Junin 766:770 arg1 virus 772:776 The highly pathogenic Junin virus 744:776 The highly pathogenic Junin virus (JUNV) 744:783 The highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. 35343792 10 124 theme neuronal 1423:1430 arg1 lines 1437:1441 neuronal cell lines 1423:1441 neuronal cell lines of mouse and human origins 1423:1468 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 13 125 theme GPC 1902:1904 arg1 TMD 1906:1908 the GPC TMD 1898:1908 the GPC TMD 1898:1908 We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. 35343792 7 126 theme corresponding 1089:1101 arg1 substitution 1109:1120 the corresponding F438I substitution 1085:1120 the corresponding F438I substitution in the GPC TMD 1085:1135 In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in the GPC TMD. 35343792 9 127 theme wild-type 1312:1320 arg1 challenge 1334:1342 wild-type MACV lethal challenge 1312:1342 wild-type MACV lethal challenge 1312:1342 Furthermore, inoculation with this mutant MACV completely protected guinea pigs from wild-type MACV lethal challenge. 35343792 12 128 theme # 1775:1775 arg1 vaccine 1778:1784 the live attenuated Candid#1 vaccine 1749:1784 the live attenuated Candid#1 vaccine 1749:1784 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 128 theme # 1775:1775 arg1 IMPORTANCE 1690:1699 IMPORTANCE 1690:1699 IMPORTANCE For arenaviruses, the only vaccine available 1690:1744 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 128 theme # 1775:1775 arg1 vaccine 1794:1800 a JUNV vaccine 1787:1800 a JUNV vaccine approved in Argentina 1787:1822 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 18 129 from replication 2540:2550 arg1 neurons 2555:2561 neurons 2555:2561 neurons 2555:2561 Another important finding from this study is that the F438I substitution in GPC TMD could substantially affect MACV replication in neurons. 35343792 10 130 theme human 1456:1460 arg1 origins 1462:1468 mouse and human origins 1446:1468 mouse and human origins 1446:1468 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 11 131 theme candidates 1643:1652 arg1 design 1615:1620 the rational design 1602:1620 the rational design of potential vaccine candidates for highly pathogenic arenaviruses 1602:1687 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 0 132 with Virus 8:12 arg1 Mutations 19:27 Mutations 19:27 Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein 19:99 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 3 133 theme N-linked 503:510 arg1 sites 519:523 specific N-linked glycan sites 494:523 specific N-linked glycan sites on the glycoprotein (GPC) 494:549 We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R-/-) mouse model. 35343792 9 134 theme lethal 1327:1332 arg1 challenge 1334:1342 wild-type MACV lethal challenge 1312:1342 wild-type MACV lethal challenge 1312:1342 Furthermore, inoculation with this mutant MACV completely protected guinea pigs from wild-type MACV lethal challenge. 35343792 19 135 theme underlying 2610:2619 arg1 mechanism 2621:2629 the underlying mechanism 2606:2629 the underlying mechanism 2606:2629 Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism. 35343792 12 136 theme live 1753:1756 arg1 vaccine 1778:1784 the live attenuated Candid#1 vaccine 1749:1784 the live attenuated Candid#1 vaccine 1749:1784 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 136 theme live 1753:1756 arg1 IMPORTANCE 1690:1699 IMPORTANCE 1690:1699 IMPORTANCE For arenaviruses, the only vaccine available 1690:1744 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 136 theme live 1753:1756 arg1 vaccine 1794:1800 a JUNV vaccine 1787:1800 a JUNV vaccine approved in Argentina 1787:1822 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 137 theme available 1736:1744 arg1 vaccine 1728:1734 the only vaccine available 1719:1744 the only vaccine available 1719:1744 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 12 137 theme available 1736:1744 arg1 arenaviruses 1705:1716 arenaviruses 1705:1716 arenaviruses 1705:1716 IMPORTANCE For arenaviruses, the only vaccine available is the live attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. 35343792 10 138 theme mouse 1446:1450 arg1 origins 1462:1468 mouse and human origins 1446:1468 mouse and human origins 1446:1468 Last, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. 35343792 11 139 theme potential 1625:1633 arg1 candidates 1643:1652 potential vaccine candidates 1625:1652 potential vaccine candidates for highly pathogenic arenaviruses 1625:1687 Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which provide insight into the rational design of potential vaccine candidates for highly pathogenic arenaviruses. 35343792 1 140 dep severe 228:233 arg1 hemorrhagic 235:245 hemorrhagic 235:245 hemorrhagic 235:245 Several highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable. 35343792 13 141 theme F427 1882:1885 arg1 residue 1887:1893 the F427 residue 1878:1893 the F427 residue in the GPC TMD 1878:1908 We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. 35343792 13 141 theme F427 1882:1885 arg1 important 1914:1922 important 1914:1922 important 1914:1922 We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. 35343792 2 142 theme New 342:344 arg1 MACV 387:390 MACV 387:390 MACV 387:390 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 2 142 theme New 342:344 arg1 virus 380:384 New World (NW) mammarenavirus Machupo virus 342:384 New World (NW) mammarenavirus Machupo virus (MACV) infection 342:401 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 8 143 theme guinea 1214:1219 arg1 pigs 1221:1224 outbred guinea pigs 1206:1224 outbred guinea pigs 1206:1224 The MACV mutant is fully attenuated in IFN-α/β and -γ R-/- mice and outbred guinea pigs. 35343792 17 144 theme pathogenic 2375:2384 arg1 arenaviruses 2386:2397 highly pathogenic arenaviruses 2368:2397 highly pathogenic arenaviruses for vaccine development 2368:2421 Thus, our studies highlight the feasibility of rational attenuation of highly pathogenic arenaviruses for vaccine development. 35343792 0 145 from Immunogenic 119:129 arg1 Models 141:146 Animal Models 134:146 Animal Models of Bolivian Hemorrhagic Fever 134:176 Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever. 35343792 18 146 theme F438I 2478:2482 arg1 substitution 2484:2495 the F438I substitution 2474:2495 the F438I substitution in GPC TMD 2474:2506 Another important finding from this study is that the F438I substitution in GPC TMD could substantially affect MACV replication in neurons. 35343792 19 147 from implication 2639:2649 arg1 tropism 2689:2695 arenavirus neural tropism 2671:2695 arenavirus neural tropism 2671:2695 Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism. 35343792 2 148 theme Machupo 372:378 arg1 MACV 387:390 MACV 387:390 MACV 387:390 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 35343792 2 148 theme Machupo 372:378 arg1 virus 380:384 New World (NW) mammarenavirus Machupo virus 342:384 New World (NW) mammarenavirus Machupo virus (MACV) infection 342:401 New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. 34981854 4 0 theme residues 626:633 arg1 mutagenesis 591:601 site-directed mutagenesis 577:601 site-directed mutagenesis of selected asparagine residues in FGFR4 577:642 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 13 1 theme FGFR4 1885:1889 arg1 localization 1869:1880 a partial localization 1859:1880 a partial localization of FGFR4 to the Golgi 1859:1902 Finally, mutation of Asn-112 caused a partial localization of FGFR4 to the Golgi. 34981854 11 2 theme asparagine 1697:1706 arg1 residues 1708:1715 the other four asparagine residues 1682:1715 the other four asparagine residues 1682:1715 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 9 3 theme glycans 1220:1226 arg1 Removal 1209:1215 Removal 1209:1215 Removal of glycans in intact cells by enzymatic deglycosylation 1209:1271 Removal of glycans in intact cells by enzymatic deglycosylation resulted in increased processing to R4-ICD. 34981854 13 4 theme Asn-112 1844:1850 arg1 mutation 1832:1839 mutation 1832:1839 mutation of Asn-112 1832:1850 Finally, mutation of Asn-112 caused a partial localization of FGFR4 to the Golgi. 34981854 11 5 theme cytoprotection 1734:1747 arg1 loss 1726:1729 a loss 1724:1729 a loss of cytoprotection by FGFR4 1724:1756 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 5 6 theme subcellular 709:719 arg1 localization 721:732 subcellular localization 709:732 subcellular localization of FGFR4 709:741 Signaling was tested through caspase activation, migration, and subcellular localization of FGFR4. 34981854 9 7 theme intact 1231:1236 arg1 cells 1238:1242 intact cells 1231:1242 intact cells 1231:1242 Removal of glycans in intact cells by enzymatic deglycosylation resulted in increased processing to R4-ICD. 34981854 2 8 theme posttranslational 283:299 arg1 processing 301:310 posttranslational processing 283:310 posttranslational processing 283:310 There are four receptor tyrosine kinases that respond to FGFs, and posttranslational processing has been demonstrated for each FGF receptor. 34981854 9 9 from Removal 1209:1215 arg1 cells 1238:1242 intact cells 1231:1242 intact cells 1231:1242 Removal of glycans in intact cells by enzymatic deglycosylation resulted in increased processing to R4-ICD. 34981854 5 10 theme caspase 674:680 arg1 activation 682:691 caspase activation 674:691 caspase activation 674:691 Signaling was tested through caspase activation, migration, and subcellular localization of FGFR4. 34981854 6 11 theme full-length 840:850 arg1 receptor 852:859 the full-length receptor 836:859 the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form 836:935 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 14 12 theme survival 1979:1986 arg1 function 1988:1995 the cell survival function 1970:1995 the cell survival function of FGFR4 and receptor glycosylation 1970:2031 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 6 13 theme glycan 925:930 arg1 form 932:935 a complex-type glycan form 910:935 a complex-type glycan form 910:935 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 12 14 theme cancer 1809:1814 arg1 cells 1816:1820 cancer cells 1809:1820 cancer cells 1809:1820 None of the glycomutants altered the migration of cancer cells. 34981854 11 15 theme apoptosis 1606:1614 arg1 resistance 1616:1625 apoptosis resistance 1606:1625 apoptosis resistance 1606:1625 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 2 16 theme tyrosine 240:247 arg1 kinases 249:255 four receptor tyrosine kinases 226:255 four receptor tyrosine kinases that respond to FGFs 226:276 There are four receptor tyrosine kinases that respond to FGFs, and posttranslational processing has been demonstrated for each FGF receptor. 34981854 7 17 theme FGFR4 1057:1061 arg1 R4-ICD 1085:1090 R4-ICD 1085:1090 R4-ICD 1085:1090 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 7 17 theme FGFR4 1057:1061 arg1 domain 1077:1082 FGFR4 intracellular domain 1057:1082 FGFR4 intracellular domain (R4-ICD) 1057:1091 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 12 18 theme glycomutants 1771:1782 arg1 None 1759:1762 None 1759:1762 None of the glycomutants 1759:1782 None of the glycomutants altered the migration of cancer cells. 34981854 8 19 located detected 1127:1134 arg2 R4-ICD 1115:1120 R4-ICD 1115:1120 R4-ICD 1115:1120 These glycoforms and R4-ICD were detected in human cholangiocarcinoma tumor samples, where R4-ICD was predominant. 34981854 8 19 located detected 1127:1134 arg2 glycoforms 1100:1109 glycoforms 1100:1109 glycoforms 1100:1109 These glycoforms and R4-ICD were detected in human cholangiocarcinoma tumor samples, where R4-ICD was predominant. 34981854 8 19 located detected 1127:1134 arg1 samples 1170:1176 human cholangiocarcinoma tumor samples 1139:1176 human cholangiocarcinoma tumor samples 1139:1176 These glycoforms and R4-ICD were detected in human cholangiocarcinoma tumor samples, where R4-ICD was predominant. 34981854 7 20 theme kinase 1035:1040 arg1 domain 1042:1047 the intracellular kinase domain 1017:1047 the intracellular kinase domain 1017:1047 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 3 21 link N-linked 391:398 arg1 glycosylation 400:412 N-linked glycosylation 391:412 N-linked glycosylation 391:412 Here, we investigated the role of N-linked glycosylation on the processing and function of FGFR4. 34981854 6 22 contain has 866:868 arg2 form 901:904 a high mannose- or hybrid-type form 870:904 a high mannose- or hybrid-type form 870:904 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 6 22 contain has 866:868 arg1 receptor 852:859 the full-length receptor 836:859 the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form 836:935 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 6 22 contain has 866:868 arg2 form 932:935 a complex-type glycan form 910:935 a complex-type glycan form 910:935 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 4 23 theme small 515:519 arg1 deglycosylation 498:512 enzymatic deglycosylation 488:512 enzymatic deglycosylation 488:512 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 4 23 theme small 515:519 arg1 inhibition 530:539 small molecule inhibition 515:539 small molecule inhibition of glycosyltransferases 515:563 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 1 24 theme growth 185:190 arg1 FGF 200:202 FGF 200:202 FGF 200:202 Recent advances in targeted treatment for cholangiocarcinoma have focused on fibroblast growth factor (FGF) signaling. 34981854 1 24 theme growth 185:190 arg1 factor 192:197 fibroblast growth factor 174:197 fibroblast growth factor (FGF) signaling 174:213 Recent advances in targeted treatment for cholangiocarcinoma have focused on fibroblast growth factor (FGF) signaling. 34981854 6 25 theme complex-type 912:923 arg1 form 932:935 a complex-type glycan form 910:935 a complex-type glycan form 910:935 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 0 26 from Glycosylation 0:12 arg1 cholangiocarcinoma 26:43 cholangiocarcinoma 26:43 cholangiocarcinoma 26:43 Glycosylation of FGFR4 in cholangiocarcinoma regulates receptor processing and cancer signaling. 34981854 11 27 theme Asn-311 1568:1574 arg1 Mutation 1526:1533 Mutation 1526:1533 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine 1526:1587 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 14 28 gly glycosylation 1925:1937 arg1 residues 1953:1960 individual residues 1942:1960 individual residues 1942:1960 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 14 28 gly glycosylation 1925:1937 arg2 residues 1953:1960 individual residues 1942:1960 individual residues 1942:1960 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 7 29 theme bands 992:996 arg1 bands 992:996 faster migrating FGFR4 bands 969:996 faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD) 969:1091 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 7 29 theme bands 992:996 arg1 set 962:964 a set 960:964 a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD) 960:1091 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 7 30 theme migrating 976:984 arg1 bands 992:996 faster migrating FGFR4 bands 969:996 faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD) 969:1091 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 10 31 theme glycosylation 1331:1343 arg1 Inhibition 1317:1326 Inhibition 1317:1326 Inhibition of glycosylation using NGI-1, an oligosaccharyltransferase inhibitor, 1317:1396 Inhibition of glycosylation using NGI-1, an oligosaccharyltransferase inhibitor, reduced both high mannose- or hybrid- and complex-type glycan forms of FGFR4, increased processing and sensitized to apoptosis. 34981854 14 32 theme extracellular 2059:2071 arg1 protease 2073:2080 an extracellular protease 2056:2080 an extracellular protease 2056:2080 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 4 33 theme site-directed 577:589 arg1 mutagenesis 591:601 site-directed mutagenesis 577:601 site-directed mutagenesis of selected asparagine residues in FGFR4 577:642 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 0 34 theme FGFR4 17:21 arg1 Glycosylation 0:12 Glycosylation 0:12 Glycosylation of FGFR4 in cholangiocarcinoma 0:43 Glycosylation of FGFR4 in cholangiocarcinoma regulates receptor processing and cancer signaling. 34981854 10 35 theme FGFR4 1469:1473 arg1 forms 1460:1464 both high mannose- or hybrid- and complex-type glycan forms 1406:1464 both high mannose- or hybrid- and complex-type glycan forms of FGFR4 1406:1473 Inhibition of glycosylation using NGI-1, an oligosaccharyltransferase inhibitor, reduced both high mannose- or hybrid- and complex-type glycan forms of FGFR4, increased processing and sensitized to apoptosis. 34981854 1 36 theme targeted 116:123 arg1 treatment 125:133 targeted treatment 116:133 targeted treatment for cholangiocarcinoma 116:156 Recent advances in targeted treatment for cholangiocarcinoma have focused on fibroblast growth factor (FGF) signaling. 34981854 3 37 theme glycosylation 400:412 arg1 role 383:386 the role 379:386 the role of N-linked glycosylation on the processing and function of FGFR4 379:452 Here, we investigated the role of N-linked glycosylation on the processing and function of FGFR4. 34981854 4 38 theme glycosyltransferases 544:563 arg1 deglycosylation 498:512 enzymatic deglycosylation 488:512 enzymatic deglycosylation 488:512 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 4 38 theme glycosyltransferases 544:563 arg1 inhibition 530:539 small molecule inhibition 515:539 small molecule inhibition of glycosyltransferases 515:563 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 10 39 theme high 1411:1414 arg1 forms 1460:1464 both high mannose- or hybrid- and complex-type glycan forms 1406:1464 both high mannose- or hybrid- and complex-type glycan forms of FGFR4 1406:1473 Inhibition of glycosylation using NGI-1, an oligosaccharyltransferase inhibitor, reduced both high mannose- or hybrid- and complex-type glycan forms of FGFR4, increased processing and sensitized to apoptosis. 34981854 0 40 theme receptor 55:62 arg1 processing 64:73 receptor processing 55:73 receptor processing 55:73 Glycosylation of FGFR4 in cholangiocarcinoma regulates receptor processing and cancer signaling. 34981854 8 41 theme human 1139:1143 arg1 samples 1170:1176 human cholangiocarcinoma tumor samples 1139:1176 human cholangiocarcinoma tumor samples 1139:1176 These glycoforms and R4-ICD were detected in human cholangiocarcinoma tumor samples, where R4-ICD was predominant. 34981854 6 42 theme hybrid-type 889:899 arg1 form 901:904 a high mannose- or hybrid-type form 870:904 a high mannose- or hybrid-type form 870:904 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 14 43 theme glycosylation 2019:2031 arg1 function 1988:1995 the cell survival function 1970:1995 the cell survival function of FGFR4 and receptor glycosylation 1970:2031 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 14 44 dep regulate 2037:2044 arg1 reduced 1962:1968 reduced 1962:1968 reduced 1962:1968 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 2 45 theme FGF 343:345 arg1 receptor 347:354 each FGF receptor 338:354 each FGF receptor 338:354 There are four receptor tyrosine kinases that respond to FGFs, and posttranslational processing has been demonstrated for each FGF receptor. 34981854 8 46 theme tumor 1164:1168 arg1 samples 1170:1176 human cholangiocarcinoma tumor samples 1139:1176 human cholangiocarcinoma tumor samples 1139:1176 These glycoforms and R4-ICD were detected in human cholangiocarcinoma tumor samples, where R4-ICD was predominant. 34981854 6 47 theme mannose- 877:884 arg1 form 901:904 a high mannose- or hybrid-type form 870:904 a high mannose- or hybrid-type form 870:904 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 10 48 theme mannose- 1416:1423 arg1 forms 1460:1464 both high mannose- or hybrid- and complex-type glycan forms 1406:1464 both high mannose- or hybrid- and complex-type glycan forms of FGFR4 1406:1473 Inhibition of glycosylation using NGI-1, an oligosaccharyltransferase inhibitor, reduced both high mannose- or hybrid- and complex-type glycan forms of FGFR4, increased processing and sensitized to apoptosis. 34981854 13 49 theme partial 1861:1867 arg1 localization 1869:1880 a partial localization 1859:1880 a partial localization of FGFR4 to the Golgi 1859:1902 Finally, mutation of Asn-112 caused a partial localization of FGFR4 to the Golgi. 34981854 6 50 theme multiple 780:787 arg1 glycoforms 789:798 multiple glycoforms 780:798 multiple glycoforms 780:798 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 1 51 from advances 104:111 arg1 treatment 125:133 targeted treatment 116:133 targeted treatment for cholangiocarcinoma 116:156 Recent advances in targeted treatment for cholangiocarcinoma have focused on fibroblast growth factor (FGF) signaling. 34981854 4 52 theme asparagine 615:624 arg1 residues 626:633 selected asparagine residues 606:633 selected asparagine residues in FGFR4 606:642 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 11 53 theme residues 1708:1715 arg1 mutation 1670:1677 simultaneous mutation 1657:1677 simultaneous mutation of the other four asparagine residues 1657:1715 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 11 53 theme residues 1708:1715 arg1 mutation 1634:1641 mutation 1634:1641 mutation of Asn-322 1634:1652 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 6 54 theme predominant 806:816 arg1 bands 818:822 predominant bands 806:822 predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form 806:935 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 10 55 theme glycan 1453:1458 arg1 forms 1460:1464 both high mannose- or hybrid- and complex-type glycan forms 1406:1464 both high mannose- or hybrid- and complex-type glycan forms of FGFR4 1406:1473 Inhibition of glycosylation using NGI-1, an oligosaccharyltransferase inhibitor, reduced both high mannose- or hybrid- and complex-type glycan forms of FGFR4, increased processing and sensitized to apoptosis. 34981854 1 56 theme factor 192:197 arg1 signaling 205:213 fibroblast growth factor (FGF) signaling 174:213 fibroblast growth factor (FGF) signaling 174:213 Recent advances in targeted treatment for cholangiocarcinoma have focused on fibroblast growth factor (FGF) signaling. 34981854 9 57 theme enzymatic 1247:1255 arg1 deglycosylation 1257:1271 enzymatic deglycosylation 1247:1271 enzymatic deglycosylation 1247:1271 Removal of glycans in intact cells by enzymatic deglycosylation resulted in increased processing to R4-ICD. 34981854 14 58 theme cell 1974:1977 arg1 function 1988:1995 the cell survival function 1970:1995 the cell survival function of FGFR4 and receptor glycosylation 1970:2031 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 12 59 theme cells 1816:1820 arg1 migration 1796:1804 the migration 1792:1804 the migration of cancer cells 1792:1820 None of the glycomutants altered the migration of cancer cells. 34981854 9 60 theme increased 1285:1293 arg1 processing 1295:1304 increased processing 1285:1304 increased processing to R4-ICD 1285:1314 Removal of glycans in intact cells by enzymatic deglycosylation resulted in increased processing to R4-ICD. 34981854 14 61 from residues 1953:1960 arg1 glycosylation 1925:1937 glycosylation 1925:1937 glycosylation at individual residues 1925:1960 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 14 62 theme individual 1942:1951 arg1 residues 1953:1960 individual residues 1942:1960 individual residues 1942:1960 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 2 63 theme receptor 231:238 arg1 kinases 249:255 four receptor tyrosine kinases 226:255 four receptor tyrosine kinases that respond to FGFs 226:276 There are four receptor tyrosine kinases that respond to FGFs, and posttranslational processing has been demonstrated for each FGF receptor. 34981854 7 64 theme intracellular 1063:1075 arg1 R4-ICD 1085:1090 R4-ICD 1085:1090 R4-ICD 1085:1090 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 7 64 theme intracellular 1063:1075 arg1 domain 1077:1082 FGFR4 intracellular domain 1057:1082 FGFR4 intracellular domain (R4-ICD) 1057:1091 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 11 65 theme Asn-290 1556:1562 arg1 Mutation 1526:1533 Mutation 1526:1533 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine 1526:1587 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 5 66 theme FGFR4 737:741 arg1 activation 682:691 caspase activation 674:691 caspase activation 674:691 Signaling was tested through caspase activation, migration, and subcellular localization of FGFR4. 34981854 5 66 theme FGFR4 737:741 arg1 localization 721:732 subcellular localization 709:732 subcellular localization of FGFR4 709:741 Signaling was tested through caspase activation, migration, and subcellular localization of FGFR4. 34981854 5 66 theme FGFR4 737:741 arg1 migration 694:702 migration 694:702 migration 694:702 Signaling was tested through caspase activation, migration, and subcellular localization of FGFR4. 34981854 11 67 theme Asn-258 1547:1553 arg1 Mutation 1526:1533 Mutation 1526:1533 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine 1526:1587 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 0 68 theme cancer 79:84 arg1 signaling 86:94 cancer signaling 79:94 cancer signaling 79:94 Glycosylation of FGFR4 in cholangiocarcinoma regulates receptor processing and cancer signaling. 34981854 4 69 theme molecule 521:528 arg1 deglycosylation 498:512 enzymatic deglycosylation 488:512 enzymatic deglycosylation 488:512 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 4 69 theme molecule 521:528 arg1 inhibition 530:539 small molecule inhibition 515:539 small molecule inhibition of glycosyltransferases 515:563 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 7 70 theme intracellular 1021:1033 arg1 domain 1042:1047 the intracellular kinase domain 1017:1047 the intracellular kinase domain 1017:1047 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 1 71 theme fibroblast 174:183 arg1 FGF 200:202 FGF 200:202 FGF 200:202 Recent advances in targeted treatment for cholangiocarcinoma have focused on fibroblast growth factor (FGF) signaling. 34981854 1 71 theme fibroblast 174:183 arg1 factor 192:197 fibroblast growth factor 174:197 fibroblast growth factor (FGF) signaling 174:213 Recent advances in targeted treatment for cholangiocarcinoma have focused on fibroblast growth factor (FGF) signaling. 34981854 7 72 dep migrating 976:984 arg1 faster 969:974 faster 969:974 faster 969:974 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 4 73 from FGFR4 638:642 arg1 mutagenesis 591:601 site-directed mutagenesis 577:601 site-directed mutagenesis of selected asparagine residues in FGFR4 577:642 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 11 74 theme other 1686:1690 arg1 residues 1708:1715 the other four asparagine residues 1682:1715 the other four asparagine residues 1682:1715 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 4 75 theme enzymatic 488:496 arg1 deglycosylation 498:512 enzymatic deglycosylation 488:512 enzymatic deglycosylation 488:512 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 4 75 theme enzymatic 488:496 arg1 inhibition 530:539 small molecule inhibition 515:539 small molecule inhibition of glycosyltransferases 515:563 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 4 76 from residues 626:633 arg1 FGFR4 638:642 FGFR4 638:642 FGFR4 638:642 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 3 77 from role 383:386 arg1 function 436:443 function 436:443 function 436:443 Here, we investigated the role of N-linked glycosylation on the processing and function of FGFR4. 34981854 3 77 from role 383:386 arg1 processing 421:430 processing 421:430 processing 421:430 Here, we investigated the role of N-linked glycosylation on the processing and function of FGFR4. 34981854 14 78 theme proteolytic 2085:2095 arg1 susceptibility 2097:2110 proteolytic susceptibility 2085:2110 proteolytic susceptibility of FGFR4 2085:2119 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 3 79 theme FGFR4 448:452 arg1 function 436:443 function 436:443 function 436:443 Here, we investigated the role of N-linked glycosylation on the processing and function of FGFR4. 34981854 3 79 theme FGFR4 448:452 arg1 processing 421:430 processing 421:430 processing 421:430 Here, we investigated the role of N-linked glycosylation on the processing and function of FGFR4. 34981854 7 80 theme FGFR4 986:990 arg1 bands 992:996 faster migrating FGFR4 bands 969:996 faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD) 969:1091 We further identified a set of faster migrating FGFR4 bands that correspond to the intracellular kinase domain, termed FGFR4 intracellular domain (R4-ICD). 34981854 1 81 theme Recent 97:102 arg1 advances 104:111 Recent advances 97:111 Recent advances in targeted treatment for cholangiocarcinoma 97:156 Recent advances in targeted treatment for cholangiocarcinoma have focused on fibroblast growth factor (FGF) signaling. 34981854 3 82 theme N-linked 391:398 arg1 glycosylation 400:412 N-linked glycosylation 391:412 N-linked glycosylation 391:412 Here, we investigated the role of N-linked glycosylation on the processing and function of FGFR4. 34981854 3 83 dep processing 421:430 arg1 the 417:419 the 417:419 the 417:419 Here, we investigated the role of N-linked glycosylation on the processing and function of FGFR4. 34981854 11 84 theme Asn-112 1538:1544 arg1 Mutation 1526:1533 Mutation 1526:1533 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine 1526:1587 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 4 85 from mutagenesis 591:601 arg1 FGFR4 638:642 FGFR4 638:642 FGFR4 638:642 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 4 86 theme selected 606:613 arg1 residues 626:633 selected asparagine residues 606:633 selected asparagine residues in FGFR4 606:642 We altered glycosylation through enzymatic deglycosylation, small molecule inhibition of glycosyltransferases, or through site-directed mutagenesis of selected asparagine residues in FGFR4. 34981854 10 87 theme oligosaccharyltransferase 1361:1385 arg1 NGI-1 1351:1355 NGI-1 1351:1355 NGI-1 1351:1355 Inhibition of glycosylation using NGI-1, an oligosaccharyltransferase inhibitor, reduced both high mannose- or hybrid- and complex-type glycan forms of FGFR4, increased processing and sensitized to apoptosis. 34981854 10 87 theme oligosaccharyltransferase 1361:1385 arg1 inhibitor 1387:1395 an oligosaccharyltransferase inhibitor 1358:1395 an oligosaccharyltransferase inhibitor 1358:1395 Inhibition of glycosylation using NGI-1, an oligosaccharyltransferase inhibitor, reduced both high mannose- or hybrid- and complex-type glycan forms of FGFR4, increased processing and sensitized to apoptosis. 34981854 0 88 gly Glycosylation 0:12 arg1 FGFR4 17:21 FGFR4 17:21 FGFR4 17:21 Glycosylation of FGFR4 in cholangiocarcinoma regulates receptor processing and cancer signaling. 34981854 6 89 contain has 776:778 arg1 FGFR4 770:774 FGFR4 770:774 FGFR4 770:774 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 6 89 contain has 776:778 arg2 glycoforms 789:798 multiple glycoforms 780:798 multiple glycoforms 780:798 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 11 90 theme simultaneous 1657:1668 arg1 mutation 1670:1677 simultaneous mutation 1657:1677 simultaneous mutation of the other four asparagine residues 1657:1715 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 8 91 theme cholangiocarcinoma 1145:1162 arg1 samples 1170:1176 human cholangiocarcinoma tumor samples 1139:1176 human cholangiocarcinoma tumor samples 1139:1176 These glycoforms and R4-ICD were detected in human cholangiocarcinoma tumor samples, where R4-ICD was predominant. 34981854 11 92 theme Asn-322 1646:1652 arg1 mutation 1670:1677 simultaneous mutation 1657:1677 simultaneous mutation of the other four asparagine residues 1657:1715 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 11 92 theme Asn-322 1646:1652 arg1 mutation 1634:1641 mutation 1634:1641 mutation of Asn-322 1634:1652 Mutation of Asn-112, Asn-258, Asn-290, or Asn-311 to glutamine modestly reduced apoptosis resistance, while mutation of Asn-322 or simultaneous mutation of the other four asparagine residues caused a loss of cytoprotection by FGFR4. 34981854 9 93 attach Removal 1209:1215 arg2 glycans 1220:1226 glycans 1220:1226 glycans 1220:1226 Removal of glycans in intact cells by enzymatic deglycosylation resulted in increased processing to R4-ICD. 34981854 9 93 attach Removal 1209:1215 arg3 cells 1238:1242 intact cells 1231:1242 intact cells 1231:1242 Removal of glycans in intact cells by enzymatic deglycosylation resulted in increased processing to R4-ICD. 34981854 14 94 theme receptor 2010:2017 arg1 glycosylation 2019:2031 receptor glycosylation 2010:2031 receptor glycosylation 2010:2031 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 14 95 theme FGFR4 2115:2119 arg1 susceptibility 2097:2110 proteolytic susceptibility 2085:2110 proteolytic susceptibility of FGFR4 2085:2119 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 14 95 theme FGFR4 2115:2119 arg1 access 2046:2051 access 2046:2051 access to an extracellular protease 2046:2080 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 10 96 theme complex-type 1440:1451 arg1 forms 1460:1464 both high mannose- or hybrid- and complex-type glycan forms 1406:1464 both high mannose- or hybrid- and complex-type glycan forms of FGFR4 1406:1473 Inhibition of glycosylation using NGI-1, an oligosaccharyltransferase inhibitor, reduced both high mannose- or hybrid- and complex-type glycan forms of FGFR4, increased processing and sensitized to apoptosis. 34981854 6 97 theme high 872:875 arg1 form 901:904 a high mannose- or hybrid-type form 870:904 a high mannose- or hybrid-type form 870:904 Our data demonstrate that FGFR4 has multiple glycoforms, with predominant bands relating to the full-length receptor that has a high mannose- or hybrid-type form and a complex-type glycan form. 34981854 14 98 theme FGFR4 2000:2004 arg1 function 1988:1995 the cell survival function 1970:1995 the cell survival function of FGFR4 and receptor glycosylation 1970:2031 Overall, preventing glycosylation at individual residues reduced the cell survival function of FGFR4 and receptor glycosylation may regulate access to an extracellular protease or proteolytic susceptibility of FGFR4. 34981854 10 99 theme hybrid- 1428:1434 arg1 forms 1460:1464 both high mannose- or hybrid- and complex-type glycan forms 1406:1464 both high mannose- or hybrid- and complex-type glycan forms of FGFR4 1406:1473 Inhibition of glycosylation using NGI-1, an oligosaccharyltransferase inhibitor, reduced both high mannose- or hybrid- and complex-type glycan forms of FGFR4, increased processing and sensitized to apoptosis. 33883138 3 0 theme LDKO 689:692 arg1 livers 694:699 LDKO livers 689:699 LDKO livers 689:699 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 4 1 theme Golgi 862:866 arg1 apparatus 868:876 the Golgi apparatus 858:876 the Golgi apparatus 858:876 This up-regulation of N-glycosylation machinery was specific to the Golgi apparatus and not the endoplasmic reticulum. 33883138 1 2 theme small 133:137 arg1 SHP 160:162 SHP 160:162 SHP 160:162 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 2 theme small 133:137 arg1 partner 151:157 small heterodimer partner 133:157 small heterodimer partner (SHP) 133:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 2 theme small 133:137 arg1 receptors 92:100 Nuclear receptors 84:100 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) 84:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 6 3 gly glycoprotein 1155:1166 arg1 glycoprotein 1155:1166 glycoprotein diversity 1155:1176 glycoprotein diversity in the liver 1155:1189 Our findings demonstrate a role for the FXR-SHP axis in maintaining glycoprotein diversity in the liver. 33883138 3 4 gly core-fucosylated 626:641 arg1 moieties 667:674 core-fucosylated and triantennary glycan moieties 626:674 core-fucosylated and triantennary glycan moieties 626:674 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 5 5 theme triglycerides 1072:1084 arg1 secretion 1033:1041 the secretion 1029:1041 the secretion of albumin, cholesterol, and triglycerides 1029:1084 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 1 6 theme heterodimer 139:149 arg1 SHP 160:162 SHP 160:162 SHP 160:162 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 6 theme heterodimer 139:149 arg1 partner 151:157 small heterodimer partner 133:157 small heterodimer partner (SHP) 133:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 6 theme heterodimer 139:149 arg1 receptors 92:100 Nuclear receptors 84:100 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) 84:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 5 7 theme dilated 978:984 arg1 ribbons 1002:1008 dilated unstacked Golgi ribbons 978:1008 dilated unstacked Golgi ribbons 978:1008 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 2 8 link N-linked 297:304 arg1 glycosylation 306:318 protein N-linked glycosylation 289:318 protein N-linked glycosylation 289:318 Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation. 33883138 3 9 theme knockout 377:384 arg1 livers 393:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 2 10 theme hepatic 253:259 arg1 axis 269:272 the hepatic FXR-SHP axis 249:272 the hepatic FXR-SHP axis 249:272 Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation. 33883138 3 11 from analysis 335:342 arg1 livers 393:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 3 12 theme St6gal1 513:519 arg1 activation 525:534 St6gal1 FXR activation 513:534 St6gal1 FXR activation 513:534 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 5 13 from ribbons 1002:1008 arg1 secretion 1033:1041 the secretion 1029:1041 the secretion of albumin, cholesterol, and triglycerides 1029:1084 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 6 14 theme FXR-SHP 1127:1133 arg1 axis 1135:1138 the FXR-SHP axis 1123:1138 the FXR-SHP axis 1123:1138 Our findings demonstrate a role for the FXR-SHP axis in maintaining glycoprotein diversity in the liver. 33883138 3 15 dep St3gal6 581:587 arg1 seen 681:684 seen 681:684 were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes 676:791 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 5 16 theme increased 917:925 arg1 complexity 934:943 The increased glycan complexity 913:943 The increased glycan complexity in the LDKO 913:955 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 3 17 theme LDKO 387:390 arg1 livers 393:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 4 18 theme machinery 832:840 arg1 up-regulation 799:811 This up-regulation 794:811 This up-regulation of N-glycosylation machinery 794:840 This up-regulation of N-glycosylation machinery was specific to the Golgi apparatus and not the endoplasmic reticulum. 33883138 2 19 theme unknown 228:234 arg1 function 236:243 a previously unknown function 215:243 a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation 215:318 Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation. 33883138 3 20 theme genes 422:426 arg1 induction 409:417 induction 409:417 induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes 409:791 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 3 21 theme double 370:375 arg1 livers 393:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 6 22 theme glycoprotein 1155:1166 arg1 diversity 1168:1176 glycoprotein diversity 1155:1176 glycoprotein diversity in the liver 1155:1189 Our findings demonstrate a role for the FXR-SHP axis in maintaining glycoprotein diversity in the liver. 33883138 0 23 theme Nuclear 0:6 arg1 FXR 18:20 FXR 18:20 FXR 18:20 Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver. 33883138 0 23 theme Nuclear 0:6 arg1 receptors 8:16 Nuclear receptors 0:16 Nuclear receptors FXR and SHP 0:28 Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver. 33883138 0 23 theme Nuclear 0:6 arg1 SHP 26:28 SHP 26:28 SHP 26:28 Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver. 33883138 5 24 theme cholesterol 1055:1065 arg1 secretion 1033:1041 the secretion 1029:1041 the secretion of albumin, cholesterol, and triglycerides 1029:1084 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 1 25 theme Nuclear 84:90 arg1 regulators 173:182 key regulators 169:182 key regulators of metabolism 169:196 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 25 theme Nuclear 84:90 arg1 partner 151:157 small heterodimer partner 133:157 small heterodimer partner (SHP) 133:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 25 theme Nuclear 84:90 arg1 receptors 92:100 Nuclear receptors 84:100 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) 84:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 25 theme Nuclear 84:90 arg1 receptor 114:121 farnesoid X receptor 102:121 farnesoid X receptor (FXR) 102:127 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 3 26 theme liver-specific 347:360 arg1 livers 393:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 3 27 theme hyperglycoforms 725:739 arg1 " 740:740 the "hyperglycoforms" 720:740 the "hyperglycoforms" preferentially localized to exosomes and lysosomes 720:791 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 2 28 theme FXR-SHP 261:267 arg1 axis 269:272 the hepatic FXR-SHP axis 249:272 the hepatic FXR-SHP axis 249:272 Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation. 33883138 3 29 theme Fxr-Shp 362:368 arg1 livers 393:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 liver-specific Fxr-Shp double knockout (LDKO) livers 347:398 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 1 30 theme farnesoid 102:110 arg1 FXR 124:126 FXR 124:126 FXR 124:126 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 30 theme farnesoid 102:110 arg1 receptors 92:100 Nuclear receptors 84:100 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) 84:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 30 theme farnesoid 102:110 arg1 receptor 114:121 farnesoid X receptor 102:121 farnesoid X receptor (FXR) 102:127 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 5 31 from alterations 1014:1024 arg1 secretion 1033:1041 the secretion 1029:1041 the secretion of albumin, cholesterol, and triglycerides 1029:1084 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 1 32 theme key 169:171 arg1 receptors 92:100 Nuclear receptors 84:100 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) 84:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 32 theme key 169:171 arg1 regulators 173:182 key regulators 169:182 key regulators of metabolism 169:196 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 6 33 from diversity 1168:1176 arg1 liver 1185:1189 the liver 1181:1189 the liver 1181:1189 Our findings demonstrate a role for the FXR-SHP axis in maintaining glycoprotein diversity in the liver. 33883138 3 34 theme core-fucosylated 626:641 arg1 moieties 667:674 core-fucosylated and triantennary glycan moieties 626:674 core-fucosylated and triantennary glycan moieties 626:674 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 3 35 theme Shp 560:562 arg1 deletion 564:571 Shp deletion 560:571 Shp deletion 560:571 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 3 36 theme Increased 601:609 arg1 percentages 611:621 Increased percentages 601:621 Increased percentages of core-fucosylated and triantennary glycan moieties 601:674 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 3 37 theme Transcriptome 321:333 arg1 analysis 335:342 Transcriptome analysis 321:342 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers 321:398 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 0 38 theme N-glycan 47:54 arg1 modifications 56:68 protein N-glycan modifications 39:68 protein N-glycan modifications in the liver 39:81 Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver. 33883138 0 39 from modifications 56:68 arg1 liver 77:81 the liver 73:81 the liver 73:81 Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver. 33883138 4 40 theme N-glycosylation 816:830 arg1 machinery 832:840 N-glycosylation machinery 816:840 N-glycosylation machinery 816:840 This up-regulation of N-glycosylation machinery was specific to the Golgi apparatus and not the endoplasmic reticulum. 33883138 3 41 from enzymes 437:443 arg1 pathway 468:474 the N-glycosylation pathway 448:474 the N-glycosylation pathway 448:474 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 1 42 theme X 112:112 arg1 FXR 124:126 FXR 124:126 FXR 124:126 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 42 theme X 112:112 arg1 receptors 92:100 Nuclear receptors 84:100 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) 84:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 42 theme X 112:112 arg1 receptor 114:121 farnesoid X receptor 102:121 farnesoid X receptor (FXR) 102:127 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 0 43 theme protein 39:45 arg1 modifications 56:68 protein N-glycan modifications 39:68 protein N-glycan modifications in the liver 39:81 Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver. 33883138 3 44 theme glycan 660:665 arg1 moieties 667:674 core-fucosylated and triantennary glycan moieties 626:674 core-fucosylated and triantennary glycan moieties 626:674 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 5 45 theme albumin 1046:1052 arg1 secretion 1033:1041 the secretion 1029:1041 the secretion of albumin, cholesterol, and triglycerides 1029:1084 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 2 46 theme N-linked 297:304 arg1 glycosylation 306:318 protein N-linked glycosylation 289:318 protein N-linked glycosylation 289:318 Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation. 33883138 3 47 theme moieties 667:674 arg1 percentages 611:621 Increased percentages 601:621 Increased percentages of core-fucosylated and triantennary glycan moieties 601:674 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 5 48 theme unstacked 986:994 arg1 ribbons 1002:1008 dilated unstacked Golgi ribbons 978:1008 dilated unstacked Golgi ribbons 978:1008 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 2 49 theme protein 289:295 arg1 glycosylation 306:318 protein N-linked glycosylation 289:318 protein N-linked glycosylation 289:318 Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation. 33883138 3 50 theme FXR 521:523 arg1 activation 525:534 St6gal1 FXR activation 513:534 St6gal1 FXR activation 513:534 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 1 51 theme metabolism 187:196 arg1 receptors 92:100 Nuclear receptors 84:100 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) 84:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 51 theme metabolism 187:196 arg1 regulators 173:182 key regulators 169:182 key regulators of metabolism 169:196 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 4 52 theme endoplasmic 890:900 arg1 reticulum 902:910 not the endoplasmic reticulum 882:910 not the endoplasmic reticulum 882:910 This up-regulation of N-glycosylation machinery was specific to the Golgi apparatus and not the endoplasmic reticulum. 33883138 5 53 theme Golgi 996:1000 arg1 ribbons 1002:1008 dilated unstacked Golgi ribbons 978:1008 dilated unstacked Golgi ribbons 978:1008 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 5 54 theme glycan 927:932 arg1 complexity 934:943 The increased glycan complexity 913:943 The increased glycan complexity in the LDKO 913:955 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 5 55 from complexity 934:943 arg1 LDKO 952:955 the LDKO 948:955 the LDKO 948:955 The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. 33883138 3 56 theme N-glycosylation 452:466 arg1 pathway 468:474 the N-glycosylation pathway 448:474 the N-glycosylation pathway 448:474 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 3 57 theme triantennary 647:658 arg1 moieties 667:674 core-fucosylated and triantennary glycan moieties 626:674 core-fucosylated and triantennary glycan moieties 626:674 Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. 33883138 0 58 dep receptors 8:16 arg1 FXR 18:20 FXR 18:20 FXR 18:20 Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver. 33883138 0 58 dep receptors 8:16 arg1 receptors 8:16 Nuclear receptors 0:16 Nuclear receptors FXR and SHP 0:28 Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver. 33883138 0 58 dep receptors 8:16 arg1 SHP 26:28 SHP 26:28 SHP 26:28 Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver. 33883138 1 59 dep receptors 92:100 arg1 SHP 160:162 SHP 160:162 SHP 160:162 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 59 dep receptors 92:100 arg1 partner 151:157 small heterodimer partner 133:157 small heterodimer partner (SHP) 133:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 59 dep receptors 92:100 arg1 FXR 124:126 FXR 124:126 FXR 124:126 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 59 dep receptors 92:100 arg1 receptors 92:100 Nuclear receptors 84:100 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) 84:163 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 33883138 1 59 dep receptors 92:100 arg1 receptor 114:121 farnesoid X receptor 102:121 farnesoid X receptor (FXR) 102:127 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. 35931119 0 0 theme HPV 112:114 arg1 infection 116:124 HPV infection 112:124 HPV infection 112:124 O-GlcNAcylation stabilizes the autophagy-initiating kinase ULK1 by inhibiting chaperone-mediated autophagy upon HPV infection. 35931119 2 1 link O-linked 324:331 arg1 transferase 366:376 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 324:376 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 324:382 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 2 1 link O-linked 324:331 arg1 OGT 379:381 OGT 379:381 OGT 379:381 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 4 2 theme autophagy 664:672 arg1 elevation 674:682 autophagy elevation 664:682 autophagy elevation 664:682 We found that upon HPV infection, Unc-51-like kinase 1 (ULK1), an autophagy-initiating kinase, is hyper-O-GlcNAcylated, stabilized, and linked with autophagy elevation. 35931119 9 3 with association 1361:1371 arg1 STX17 1386:1390 STX17 1386:1390 STX17 1386:1390 Furthermore, ULK1-2A mutants attenuate the association of ULK1 with STX17, which is vital for the fusion between autophagosomes and lysosomes. 35931119 3 4 theme O-GlcNAcylation 476:490 arg1 effects 465:471 the effects 461:471 the effects of O-GlcNAcylation on HPV-positive HNSCCs 461:513 Here, we focus on the effects of O-GlcNAcylation on HPV-positive HNSCCs. 35931119 6 5 theme chaperone-mediated 967:984 arg1 CMA 997:999 CMA 997:999 CMA 997:999 It has been demonstrated that PKCα mediates phosphorylation of ULK1 at Ser423, which attenuates its stability by shunting ULK1 to the chaperone-mediated autophagy (CMA) pathway. 35931119 6 5 theme chaperone-mediated 967:984 arg1 autophagy 986:994 chaperone-mediated autophagy 967:994 the chaperone-mediated autophagy (CMA) pathway 963:1008 It has been demonstrated that PKCα mediates phosphorylation of ULK1 at Ser423, which attenuates its stability by shunting ULK1 to the chaperone-mediated autophagy (CMA) pathway. 35931119 6 6 theme ULK1 896:899 arg1 phosphorylation 877:891 phosphorylation 877:891 phosphorylation of ULK1 877:899 It has been demonstrated that PKCα mediates phosphorylation of ULK1 at Ser423, which attenuates its stability by shunting ULK1 to the chaperone-mediated autophagy (CMA) pathway. 35931119 12 7 theme patient 1881:1887 arg1 survival 1889:1896 HPV-positive HNSCC patient survival 1862:1896 HPV-positive HNSCC patient survival 1862:1896 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 stabilizes ULK1, which might underlie the molecular mechanism of HPV-positive HNSCC patient survival. 35931119 1 8 theme head 175:178 arg1 HNSCCs 215:220 HNSCCs 215:220 HNSCCs 215:220 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 1 8 theme head 175:178 arg1 carcinomas 203:212 head and neck squamous cell carcinomas 175:212 head and neck squamous cell carcinomas (HNSCCs) 175:221 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 4 9 theme Unc-51-like 550:560 arg1 kinase 562:567 Unc-51-like kinase 1 550:569 Unc-51-like kinase 1 (ULK1) 550:576 We found that upon HPV infection, Unc-51-like kinase 1 (ULK1), an autophagy-initiating kinase, is hyper-O-GlcNAcylated, stabilized, and linked with autophagy elevation. 35931119 4 9 theme Unc-51-like 550:560 arg1 ULK1 572:575 ULK1 572:575 ULK1 572:575 We found that upon HPV infection, Unc-51-like kinase 1 (ULK1), an autophagy-initiating kinase, is hyper-O-GlcNAcylated, stabilized, and linked with autophagy elevation. 35931119 4 9 theme Unc-51-like 550:560 arg1 kinase 603:608 an autophagy-initiating kinase 579:608 an autophagy-initiating kinase 579:608 We found that upon HPV infection, Unc-51-like kinase 1 (ULK1), an autophagy-initiating kinase, is hyper-O-GlcNAcylated, stabilized, and linked with autophagy elevation. 35931119 5 10 from Ser409 757:762 arg1 O-GlcNAcylated 739:752 O-GlcNAcylated 739:752 O-GlcNAcylated 739:752 Through mass spectrometry, we identified that ULK1 is O-GlcNAcylated at Ser409, which is distinct from the previously reported Thr635/Thr754 sites. 35931119 12 11 theme ULK1 1763:1766 arg1 O-GlcNAcylation 1744:1758 O-GlcNAcylation 1744:1758 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 1744:1795 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 stabilizes ULK1, which might underlie the molecular mechanism of HPV-positive HNSCC patient survival. 35931119 12 12 theme survival 1889:1896 arg1 mechanism 1849:1857 the molecular mechanism 1835:1857 the molecular mechanism of HPV-positive HNSCC patient survival 1835:1896 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 stabilizes ULK1, which might underlie the molecular mechanism of HPV-positive HNSCC patient survival. 35931119 2 13 theme E6/E7 278:282 arg1 transduction 284:295 E6/E7 transduction 278:295 E6/E7 transduction 278:295 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 11 14 theme environmental 1721:1733 arg1 changes 1735:1741 environmental changes 1721:1741 environmental changes 1721:1741 Overall, our work demonstrates that O-GlcNAcylation of ULK1 is altered in response to environmental changes. 35931119 8 15 theme chaperone 1265:1273 arg1 HSC70 1275:1279 the CMA chaperone HSC70 1257:1279 the CMA chaperone HSC70 (heat shock cognate 70 kDa protein) 1257:1315 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 15 theme chaperone 1265:1273 arg1 protein 1308:1314 heat shock cognate 70 kDa protein 1282:1314 heat shock cognate 70 kDa protein 1282:1314 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 7 16 theme Ser409Ser410 1062:1073 arg1 O-GlcNAcylation 1075:1089 ULK1 Ser409Ser410 O-GlcNAcylation 1057:1089 ULK1 Ser409Ser410 O-GlcNAcylation 1057:1089 Using biochemical assays, we demonstrate that ULK1 Ser409Ser410 O-GlcNAcylation antagonizes its phosphorylation at Ser423. 35931119 5 17 theme reported 803:810 arg1 sites 826:830 the previously reported Thr635/Thr754 sites 788:830 the previously reported Thr635/Thr754 sites 788:830 Through mass spectrometry, we identified that ULK1 is O-GlcNAcylated at Ser409, which is distinct from the previously reported Thr635/Thr754 sites. 35931119 12 18 from Ser410 1790:1795 arg1 O-GlcNAcylation 1744:1758 O-GlcNAcylation 1744:1758 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 1744:1795 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 stabilizes ULK1, which might underlie the molecular mechanism of HPV-positive HNSCC patient survival. 35931119 2 19 theme OGT 389:391 arg1 substrates 393:402 OGT substrates 389:402 OGT substrates affected by this increase 389:428 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 8 20 theme Ser409A 1157:1163 arg1 mutations 1144:1152 mutations 1144:1152 mutations of Ser409A and its neighboring site Ser410A (2A) 1144:1201 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 21 with interaction 1240:1250 arg1 HSC70 1275:1279 the CMA chaperone HSC70 1257:1279 the CMA chaperone HSC70 (heat shock cognate 70 kDa protein) 1257:1315 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 21 with interaction 1240:1250 arg1 protein 1308:1314 heat shock cognate 70 kDa protein 1282:1314 heat shock cognate 70 kDa protein 1282:1314 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 1 22 theme neck 184:187 arg1 HNSCCs 215:220 HNSCCs 215:220 HNSCCs 215:220 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 1 22 theme neck 184:187 arg1 carcinomas 203:212 head and neck squamous cell carcinomas 175:212 head and neck squamous cell carcinomas (HNSCCs) 175:221 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 8 23 theme neighboring 1173:1183 arg1 2A 1199:1200 2A 1199:1200 2A 1199:1200 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 23 theme neighboring 1173:1183 arg1 Ser410A 1190:1196 its neighboring site Ser410A 1169:1196 its neighboring site Ser410A (2A) 1169:1201 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 12 24 theme HNSCC 1875:1879 arg1 survival 1889:1896 HPV-positive HNSCC patient survival 1862:1896 HPV-positive HNSCC patient survival 1862:1896 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 stabilizes ULK1, which might underlie the molecular mechanism of HPV-positive HNSCC patient survival. 35931119 12 25 from Ser409 1771:1776 arg1 O-GlcNAcylation 1744:1758 O-GlcNAcylation 1744:1758 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 1744:1795 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 stabilizes ULK1, which might underlie the molecular mechanism of HPV-positive HNSCC patient survival. 35931119 10 26 theme Genome 1484:1489 arg1 database 1504:1511 The Cancer Genome Atlas (TCGA) database 1473:1511 The Cancer Genome Atlas (TCGA) database 1473:1511 Analysis of The Cancer Genome Atlas (TCGA) database reveals that ULK1 is upregulated in HPV-positive HNSCCs, and its level positively correlates with HNSCC patient survival. 35931119 1 27 theme squamous 189:196 arg1 HNSCCs 215:220 HNSCCs 215:220 HNSCCs 215:220 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 1 27 theme squamous 189:196 arg1 carcinomas 203:212 head and neck squamous cell carcinomas 175:212 head and neck squamous cell carcinomas (HNSCCs) 175:221 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 10 28 theme HPV-positive 1549:1560 arg1 HNSCCs 1562:1567 HPV-positive HNSCCs 1549:1567 HPV-positive HNSCCs 1549:1567 Analysis of The Cancer Genome Atlas (TCGA) database reveals that ULK1 is upregulated in HPV-positive HNSCCs, and its level positively correlates with HNSCC patient survival. 35931119 4 29 theme HPV 535:537 arg1 infection 539:547 HPV infection 535:547 HPV infection 535:547 We found that upon HPV infection, Unc-51-like kinase 1 (ULK1), an autophagy-initiating kinase, is hyper-O-GlcNAcylated, stabilized, and linked with autophagy elevation. 35931119 7 30 theme ULK1 1057:1060 arg1 O-GlcNAcylation 1075:1089 ULK1 Ser409Ser410 O-GlcNAcylation 1057:1089 ULK1 Ser409Ser410 O-GlcNAcylation 1057:1089 Using biochemical assays, we demonstrate that ULK1 Ser409Ser410 O-GlcNAcylation antagonizes its phosphorylation at Ser423. 35931119 3 31 from effects 465:471 arg1 HNSCCs 508:513 HPV-positive HNSCCs 495:513 HPV-positive HNSCCs 495:513 Here, we focus on the effects of O-GlcNAcylation on HPV-positive HNSCCs. 35931119 1 32 theme cell 198:201 arg1 HNSCCs 215:220 HNSCCs 215:220 HNSCCs 215:220 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 1 32 theme cell 198:201 arg1 carcinomas 203:212 head and neck squamous cell carcinomas 175:212 head and neck squamous cell carcinomas (HNSCCs) 175:221 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 0 33 theme autophagy-initiating 31:50 arg1 ULK1 59:62 the autophagy-initiating kinase ULK1 27:62 the autophagy-initiating kinase ULK1 27:62 O-GlcNAcylation stabilizes the autophagy-initiating kinase ULK1 by inhibiting chaperone-mediated autophagy upon HPV infection. 35931119 1 34 theme Human 127:131 arg1 HPVs 151:154 HPVs 151:154 HPVs 151:154 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 1 34 theme Human 127:131 arg1 papillomaviruses 133:148 Human papillomaviruses 127:148 Human papillomaviruses (HPVs) 127:155 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 1 35 theme carcinomas 203:212 arg1 subset 165:170 a subset 163:170 a subset of head and neck squamous cell carcinomas (HNSCCs) 163:221 Human papillomaviruses (HPVs) cause a subset of head and neck squamous cell carcinomas (HNSCCs). 35931119 8 36 theme site 1185:1188 arg1 2A 1199:1200 2A 1199:1200 2A 1199:1200 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 36 theme site 1185:1188 arg1 Ser410A 1190:1196 its neighboring site Ser410A 1169:1196 its neighboring site Ser410A (2A) 1169:1201 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 37 theme cognate 1293:1299 arg1 HSC70 1275:1279 the CMA chaperone HSC70 1257:1279 the CMA chaperone HSC70 (heat shock cognate 70 kDa protein) 1257:1315 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 37 theme cognate 1293:1299 arg1 protein 1308:1314 heat shock cognate 70 kDa protein 1282:1314 heat shock cognate 70 kDa protein 1282:1314 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 4 38 theme autophagy-initiating 582:601 arg1 kinase 603:608 an autophagy-initiating kinase 579:608 an autophagy-initiating kinase 579:608 We found that upon HPV infection, Unc-51-like kinase 1 (ULK1), an autophagy-initiating kinase, is hyper-O-GlcNAcylated, stabilized, and linked with autophagy elevation. 35931119 4 38 theme autophagy-initiating 582:601 arg1 kinase 562:567 Unc-51-like kinase 1 550:569 Unc-51-like kinase 1 (ULK1) 550:576 We found that upon HPV infection, Unc-51-like kinase 1 (ULK1), an autophagy-initiating kinase, is hyper-O-GlcNAcylated, stabilized, and linked with autophagy elevation. 35931119 12 39 theme molecular 1839:1847 arg1 mechanism 1849:1857 the molecular mechanism 1835:1857 the molecular mechanism of HPV-positive HNSCC patient survival 1835:1896 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 stabilizes ULK1, which might underlie the molecular mechanism of HPV-positive HNSCC patient survival. 35931119 8 40 theme shock 1287:1291 arg1 HSC70 1275:1279 the CMA chaperone HSC70 1257:1279 the CMA chaperone HSC70 (heat shock cognate 70 kDa protein) 1257:1315 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 40 theme shock 1287:1291 arg1 protein 1308:1314 heat shock cognate 70 kDa protein 1282:1314 heat shock cognate 70 kDa protein 1282:1314 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 41 theme stable 1220:1225 arg1 ULK1 1210:1213 ULK1 1210:1213 ULK1 less stable 1210:1225 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 5 42 theme Thr635/Thr754 812:824 arg1 sites 826:830 the previously reported Thr635/Thr754 sites 788:830 the previously reported Thr635/Thr754 sites 788:830 Through mass spectrometry, we identified that ULK1 is O-GlcNAcylated at Ser409, which is distinct from the previously reported Thr635/Thr754 sites. 35931119 0 43 theme kinase 52:57 arg1 ULK1 59:62 the autophagy-initiating kinase ULK1 27:62 the autophagy-initiating kinase ULK1 27:62 O-GlcNAcylation stabilizes the autophagy-initiating kinase ULK1 by inhibiting chaperone-mediated autophagy upon HPV infection. 35931119 2 44 theme transferase 366:376 arg1 abundance 311:319 the abundance 307:319 the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 307:382 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 5 45 theme mass 693:696 arg1 spectrometry 698:709 mass spectrometry 693:709 mass spectrometry 693:709 Through mass spectrometry, we identified that ULK1 is O-GlcNAcylated at Ser409, which is distinct from the previously reported Thr635/Thr754 sites. 35931119 8 46 theme Ser410A 1190:1196 arg1 mutations 1144:1152 mutations 1144:1152 mutations of Ser409A and its neighboring site Ser410A (2A) 1144:1201 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 10 47 theme patient 1617:1623 arg1 survival 1625:1632 HNSCC patient survival 1611:1632 HNSCC patient survival 1611:1632 Analysis of The Cancer Genome Atlas (TCGA) database reveals that ULK1 is upregulated in HPV-positive HNSCCs, and its level positively correlates with HNSCC patient survival. 35931119 12 48 theme HPV-positive 1862:1873 arg1 survival 1889:1896 HPV-positive HNSCC patient survival 1862:1896 HPV-positive HNSCC patient survival 1862:1896 O-GlcNAcylation of ULK1 at Ser409 and perhaps Ser410 stabilizes ULK1, which might underlie the molecular mechanism of HPV-positive HNSCC patient survival. 35931119 9 49 theme ULK1-2A 1331:1337 arg1 mutants 1339:1345 ULK1-2A mutants 1331:1345 ULK1-2A mutants 1331:1345 Furthermore, ULK1-2A mutants attenuate the association of ULK1 with STX17, which is vital for the fusion between autophagosomes and lysosomes. 35931119 10 50 theme Atlas 1491:1495 arg1 database 1504:1511 The Cancer Genome Atlas (TCGA) database 1473:1511 The Cancer Genome Atlas (TCGA) database 1473:1511 Analysis of The Cancer Genome Atlas (TCGA) database reveals that ULK1 is upregulated in HPV-positive HNSCCs, and its level positively correlates with HNSCC patient survival. 35931119 5 51 from sites 826:830 arg1 distinct 774:781 distinct 774:781 distinct 774:781 Through mass spectrometry, we identified that ULK1 is O-GlcNAcylated at Ser409, which is distinct from the previously reported Thr635/Thr754 sites. 35931119 2 52 theme O-GlcNAc 356:363 arg1 transferase 366:376 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 324:376 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 324:382 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 2 52 theme O-GlcNAc 356:363 arg1 OGT 379:381 OGT 379:381 OGT 379:381 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 7 53 theme biochemical 1017:1027 arg1 assays 1029:1034 biochemical assays 1017:1034 biochemical assays 1017:1034 Using biochemical assays, we demonstrate that ULK1 Ser409Ser410 O-GlcNAcylation antagonizes its phosphorylation at Ser423. 35931119 10 54 theme TCGA 1498:1501 arg1 database 1504:1511 The Cancer Genome Atlas (TCGA) database 1473:1511 The Cancer Genome Atlas (TCGA) database 1473:1511 Analysis of The Cancer Genome Atlas (TCGA) database reveals that ULK1 is upregulated in HPV-positive HNSCCs, and its level positively correlates with HNSCC patient survival. 35931119 8 55 theme CMA 1261:1263 arg1 HSC70 1275:1279 the CMA chaperone HSC70 1257:1279 the CMA chaperone HSC70 (heat shock cognate 70 kDa protein) 1257:1315 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 55 theme CMA 1261:1263 arg1 protein 1308:1314 heat shock cognate 70 kDa protein 1282:1314 heat shock cognate 70 kDa protein 1282:1314 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 10 56 theme Cancer 1477:1482 arg1 database 1504:1511 The Cancer Genome Atlas (TCGA) database 1473:1511 The Cancer Genome Atlas (TCGA) database 1473:1511 Analysis of The Cancer Genome Atlas (TCGA) database reveals that ULK1 is upregulated in HPV-positive HNSCCs, and its level positively correlates with HNSCC patient survival. 35931119 11 57 theme ULK1 1690:1693 arg1 O-GlcNAcylation 1671:1685 O-GlcNAcylation 1671:1685 O-GlcNAcylation of ULK1 1671:1693 Overall, our work demonstrates that O-GlcNAcylation of ULK1 is altered in response to environmental changes. 35931119 2 58 theme oncogene 263:270 arg1 E6 272:273 HPV16 oncogene E6 257:273 HPV16 oncogene E6 257:273 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 2 59 theme β-N-acetylglucosamine 333:353 arg1 transferase 366:376 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 324:376 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 324:382 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 2 59 theme β-N-acetylglucosamine 333:353 arg1 OGT 379:381 OGT 379:381 OGT 379:381 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 2 60 theme HPV16 257:261 arg1 E6 272:273 HPV16 oncogene E6 257:273 HPV16 oncogene E6 257:273 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 2 61 theme O-linked 324:331 arg1 transferase 366:376 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase 324:376 O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) 324:382 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 2 61 theme O-linked 324:331 arg1 OGT 379:381 OGT 379:381 OGT 379:381 Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), but OGT substrates affected by this increase are unclear. 35931119 8 62 theme 70 kDa 1301:1306 arg1 HSC70 1275:1279 the CMA chaperone HSC70 1257:1279 the CMA chaperone HSC70 (heat shock cognate 70 kDa protein) 1257:1315 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 62 theme 70 kDa 1301:1306 arg1 protein 1308:1314 heat shock cognate 70 kDa protein 1282:1314 heat shock cognate 70 kDa protein 1282:1314 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 11 63 gly O-GlcNAcylation 1671:1685 arg1 response 1709:1716 response 1709:1716 response to environmental changes 1709:1741 Overall, our work demonstrates that O-GlcNAcylation of ULK1 is altered in response to environmental changes. 35931119 10 64 theme database 1504:1511 arg1 Analysis 1461:1468 Analysis 1461:1468 Analysis of The Cancer Genome Atlas (TCGA) database 1461:1511 Analysis of The Cancer Genome Atlas (TCGA) database reveals that ULK1 is upregulated in HPV-positive HNSCCs, and its level positively correlates with HNSCC patient survival. 35931119 3 65 theme HPV-positive 495:506 arg1 HNSCCs 508:513 HPV-positive HNSCCs 495:513 HPV-positive HNSCCs 495:513 Here, we focus on the effects of O-GlcNAcylation on HPV-positive HNSCCs. 35931119 10 66 theme HNSCC 1611:1615 arg1 survival 1625:1632 HNSCC patient survival 1611:1632 HNSCC patient survival 1611:1632 Analysis of The Cancer Genome Atlas (TCGA) database reveals that ULK1 is upregulated in HPV-positive HNSCCs, and its level positively correlates with HNSCC patient survival. 35931119 0 67 theme chaperone-mediated 78:95 arg1 autophagy 97:105 chaperone-mediated autophagy 78:105 chaperone-mediated autophagy 78:105 O-GlcNAcylation stabilizes the autophagy-initiating kinase ULK1 by inhibiting chaperone-mediated autophagy upon HPV infection. 35931119 7 68 from Ser423 1126:1131 arg1 phosphorylation 1107:1121 its phosphorylation 1103:1121 its phosphorylation at Ser423 1103:1131 Using biochemical assays, we demonstrate that ULK1 Ser409Ser410 O-GlcNAcylation antagonizes its phosphorylation at Ser423. 35931119 9 69 theme ULK1 1376:1379 arg1 association 1361:1371 the association 1357:1371 the association of ULK1 with STX17, which is vital for the fusion between autophagosomes and lysosomes 1357:1458 Furthermore, ULK1-2A mutants attenuate the association of ULK1 with STX17, which is vital for the fusion between autophagosomes and lysosomes. 35931119 8 70 theme heat 1282:1285 arg1 HSC70 1275:1279 the CMA chaperone HSC70 1257:1279 the CMA chaperone HSC70 (heat shock cognate 70 kDa protein) 1257:1315 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 8 70 theme heat 1282:1285 arg1 protein 1308:1314 heat shock cognate 70 kDa protein 1282:1314 heat shock cognate 70 kDa protein 1282:1314 Moreover, mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone HSC70 (heat shock cognate 70 kDa protein). 35931119 6 71 theme autophagy 986:994 arg1 pathway 1002:1008 the chaperone-mediated autophagy (CMA) pathway 963:1008 the chaperone-mediated autophagy (CMA) pathway 963:1008 It has been demonstrated that PKCα mediates phosphorylation of ULK1 at Ser423, which attenuates its stability by shunting ULK1 to the chaperone-mediated autophagy (CMA) pathway. 33716169 9 0 theme histone 1638:1644 arg1 deacetylase 1646:1656 histone deacetylase 1 1638:1658 histone deacetylase 1 1638:1658 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 6 1 from culture 1232:1238 arg1 labeling 1200:1207 stable isotopic labeling 1184:1207 stable isotopic labeling of amino acids in cell culture 1184:1238 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 1 2 theme intracellular 173:185 arg1 proteins 187:194 intracellular proteins 173:194 intracellular proteins 173:194 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 6 3 theme heavy 1157:1161 arg1 lysine 1163:1168 heavy lysine 1157:1168 heavy lysine 1157:1168 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 3 4 theme proteins 571:578 arg1 glycosylation 547:559 glycosylation 547:559 glycosylation of target proteins and signaling pathways 547:601 It remains unclear how just two enzymes can be specifically controlled to affect glycosylation of target proteins and signaling pathways both basally and in response to stress. 33716169 3 5 dep both 603:606 arg1 basally 608:614 basally 608:614 basally 608:614 It remains unclear how just two enzymes can be specifically controlled to affect glycosylation of target proteins and signaling pathways both basally and in response to stress. 33716169 9 6 theme reaction 1683:1690 arg1 monitoring 1692:1701 parallel reaction monitoring 1674:1701 parallel reaction monitoring 1674:1701 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 7 7 theme hydrogen 1352:1359 arg1 peroxide 1361:1368 hydrogen peroxide 1352:1368 hydrogen peroxide stress 1352:1375 In total, more than 130 proteins were found to interact with OGT, many of which change their association upon hydrogen peroxide stress. 33716169 10 8 theme domain 1965:1970 arg1 architecture 1972:1983 varied domain architecture 1958:1983 varied domain architecture 1958:1983 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 7 9 located found 1280:1284 arg2 proteins 1266:1273 more than 130 proteins 1252:1273 more than 130 proteins 1252:1273 In total, more than 130 proteins were found to interact with OGT, many of which change their association upon hydrogen peroxide stress. 33716169 7 9 located found 1280:1284 arg1 total 1245:1249 total 1245:1249 total 1245:1249 In total, more than 130 proteins were found to interact with OGT, many of which change their association upon hydrogen peroxide stress. 33716169 11 10 theme specific 2066:2073 arg1 interactors 2075:2085 unique and specific interactors 2055:2085 unique and specific interactors 2055:2085 Together these data demonstrate that OGT interacts with unique and specific interactors in a stress-responsive manner. 33716169 8 11 theme major 1405:1409 arg1 cleavage 1415:1422 the major OGT cleavage and glycosylation substrate 1401:1450 cleavage 1415:1422 These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation after stress. 33716169 8 11 theme major 1405:1409 arg1 factor 1463:1468 host cell factor 1 1453:1470 host cell factor 1 1453:1470 These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation after stress. 33716169 6 12 theme cell 1227:1230 arg1 culture 1232:1238 cell culture 1227:1238 cell culture 1227:1238 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 10 13 contain contain 1950:1956 arg1 targets 1937:1943 previously characterized glycosylation targets 1898:1943 previously characterized glycosylation targets that contain varied domain architecture and function 1898:1996 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 13 contain contain 1950:1956 arg1 them 1889:1892 them 1889:1892 them 1889:1892 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 13 contain contain 1950:1956 arg1 % 1884:1884 64% 1882:1884 64% of them 1882:1892 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 13 contain contain 1950:1956 arg2 function 1989:1996 function 1989:1996 function 1989:1996 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 13 contain contain 1950:1956 arg2 architecture 1972:1983 varied domain architecture 1958:1983 varied domain architecture 1958:1983 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 4 14 theme Several 643:649 arg1 lines 651:655 Several lines 643:655 Several lines of evidence 643:667 Several lines of evidence suggest that protein interactors regulate these responses by affecting OGT and O-GlcNAcase activity, localization, and substrate specificity. 33716169 5 15 used used 895:898 arg2 we 887:888 we 887:888 we 887:888 To provide insight into the mechanisms by which OGT function is controlled, we have used quantitative proteomics to define OGT's basal and stress-induced interactomes. 33716169 5 16 theme OGT 859:861 arg1 function 863:870 OGT function 859:870 OGT function 859:870 To provide insight into the mechanisms by which OGT function is controlled, we have used quantitative proteomics to define OGT's basal and stress-induced interactomes. 33716169 6 17 theme acids 1218:1222 arg1 labeling 1200:1207 stable isotopic labeling 1184:1207 stable isotopic labeling of amino acids in cell culture 1184:1238 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 11 18 theme stress-responsive 2092:2108 arg1 manner 2110:2115 a stress-responsive manner 2090:2115 a stress-responsive manner 2090:2115 Together these data demonstrate that OGT interacts with unique and specific interactors in a stress-responsive manner. 33716169 3 19 theme signaling 584:592 arg1 pathways 594:601 signaling pathways 584:601 signaling pathways 584:601 It remains unclear how just two enzymes can be specifically controlled to affect glycosylation of target proteins and signaling pathways both basally and in response to stress. 33716169 9 20 theme discovery-based 1728:1742 arg1 labeling 1760:1767 our discovery-based stable isotopic labeling 1724:1767 our discovery-based stable isotopic labeling of amino acids 1724:1782 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 8 21 theme glycosylation 1428:1440 arg1 substrate 1442:1450 the major OGT cleavage and glycosylation substrate 1401:1450 substrate 1442:1450 These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation after stress. 33716169 10 22 theme proteins 1835:1842 arg1 interactors 1869:1879 novel OGT interactors 1859:1879 novel OGT interactors 1859:1879 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 22 theme proteins 1835:1842 arg1 majority 1823:1830 the majority 1819:1830 the majority of proteins identified 1819:1853 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 3 23 dep affect 540:545 arg1 both 603:606 both 603:606 both 603:606 It remains unclear how just two enzymes can be specifically controlled to affect glycosylation of target proteins and signaling pathways both basally and in response to stress. 33716169 3 23 dep affect 540:545 arg1 response 623:630 response 623:630 response to stress 623:640 It remains unclear how just two enzymes can be specifically controlled to affect glycosylation of target proteins and signaling pathways both basally and in response to stress. 33716169 6 24 theme OGT 1041:1043 arg1 lysates 1090:1096 OGT WT, null, and hydrogen peroxide-treated cell lysates 1041:1096 OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture) 1041:1239 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 9 25 theme isotopic 1751:1758 arg1 labeling 1760:1767 our discovery-based stable isotopic labeling 1724:1767 our discovery-based stable isotopic labeling of amino acids 1724:1782 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 6 26 theme isotopic 1191:1198 arg1 labeling 1200:1207 stable isotopic labeling 1184:1207 stable isotopic labeling of amino acids in cell culture 1184:1238 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 4 27 theme protein 682:688 arg1 interactors 690:700 protein interactors 682:700 protein interactors 682:700 Several lines of evidence suggest that protein interactors regulate these responses by affecting OGT and O-GlcNAcase activity, localization, and substrate specificity. 33716169 8 28 theme cell 1458:1461 arg1 cleavage 1415:1422 the major OGT cleavage and glycosylation substrate 1401:1450 cleavage 1415:1422 These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation after stress. 33716169 8 28 theme cell 1458:1461 arg1 factor 1463:1468 host cell factor 1 1453:1470 host cell factor 1 1453:1470 These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation after stress. 33716169 1 29 theme residues 161:168 arg1 modification 115:126 The dynamic modification 103:126 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) 103:242 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 9 30 theme acids 1778:1782 arg1 labeling 1760:1767 our discovery-based stable isotopic labeling 1724:1767 our discovery-based stable isotopic labeling of amino acids 1724:1782 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 1 31 link O-linked 199:206 arg1 N-acetyl-β-D-glucosamine 208:231 O-linked N-acetyl-β-D-glucosamine 199:231 O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) 199:242 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 1 31 link O-linked 199:206 arg1 O-GlcNAc 234:241 O-GlcNAc 234:241 O-GlcNAc 234:241 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 9 32 theme well-characterized 1553:1570 arg1 interactors 1572:1582 less well-characterized interactors 1548:1582 less well-characterized interactors 1548:1582 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 9 32 theme well-characterized 1553:1570 arg1 dehydrogenase 1620:1632 glyceraldehyde 3-phosphate dehydrogenase 1593:1632 glyceraldehyde 3-phosphate dehydrogenase 1593:1632 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 9 32 theme well-characterized 1553:1570 arg1 deacetylase 1646:1656 histone deacetylase 1 1638:1658 histone deacetylase 1 1638:1658 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 0 33 theme Oxidative 85:93 arg1 Stress 95:100 Oxidative Stress 85:100 Oxidative Stress 85:100 Quantitative Proteomics Reveals that the OGT Interactome Is Remodeled in Response to Oxidative Stress. 33716169 1 34 theme specific 131:138 arg1 proteins 187:194 intracellular proteins 173:194 intracellular proteins 173:194 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 1 34 theme specific 131:138 arg1 residues 161:168 specific serine and threonine residues 131:168 specific serine and threonine residues of intracellular proteins 131:194 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 9 35 theme cell 1787:1790 arg1 approach 1800:1807 cell culture approach 1787:1807 cell culture approach 1787:1807 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 7 36 theme OGT 1303:1305 arg1 many 1308:1311 many 1308:1311 many 1308:1311 In total, more than 130 proteins were found to interact with OGT, many of which change their association upon hydrogen peroxide stress. 33716169 7 36 theme OGT 1303:1305 arg1 OGT 1303:1305 OGT 1303:1305 OGT 1303:1305 In total, more than 130 proteins were found to interact with OGT, many of which change their association upon hydrogen peroxide stress. 33716169 0 37 theme Quantitative 0:11 arg1 Proteomics 13:22 Quantitative Proteomics 0:22 Quantitative Proteomics 0:22 Quantitative Proteomics Reveals that the OGT Interactome Is Remodeled in Response to Oxidative Stress. 33716169 5 38 theme basal 940:944 arg1 interactomes 965:976 OGT's basal and stress-induced interactomes 934:976 OGT's basal and stress-induced interactomes 934:976 To provide insight into the mechanisms by which OGT function is controlled, we have used quantitative proteomics to define OGT's basal and stress-induced interactomes. 33716169 1 39 theme stress 305:310 arg1 models 312:317 stress models 305:317 stress models 305:317 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 5 40 theme stress-induced 950:963 arg1 interactomes 965:976 OGT's basal and stress-induced interactomes 934:976 OGT's basal and stress-induced interactomes 934:976 To provide insight into the mechanisms by which OGT function is controlled, we have used quantitative proteomics to define OGT's basal and stress-induced interactomes. 33716169 10 41 theme OGT 1865:1867 arg1 interactors 1869:1879 novel OGT interactors 1859:1879 novel OGT interactors 1859:1879 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 41 theme OGT 1865:1867 arg1 majority 1823:1830 the majority 1819:1830 the majority of proteins identified 1819:1853 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 2 42 theme substrates 454:463 arg1 thousands 441:449 thousands 441:449 thousands of substrates 441:463 The O-GlcNAc transferase (OGT) and the O-GlcNAcase are the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates. 33716169 9 43 theme 3-phosphate 1608:1618 arg1 dehydrogenase 1620:1632 glyceraldehyde 3-phosphate dehydrogenase 1593:1632 glyceraldehyde 3-phosphate dehydrogenase 1593:1632 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 10 44 theme them 1889:1892 arg1 targets 1937:1943 previously characterized glycosylation targets 1898:1943 previously characterized glycosylation targets that contain varied domain architecture and function 1898:1996 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 44 theme them 1889:1892 arg1 them 1889:1892 them 1889:1892 them 1889:1892 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 44 theme them 1889:1892 arg1 % 1884:1884 64% 1882:1884 64% of them 1882:1892 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 11 45 theme unique 2055:2060 arg1 interactors 2075:2085 unique and specific interactors 2055:2085 unique and specific interactors 2055:2085 Together these data demonstrate that OGT interacts with unique and specific interactors in a stress-responsive manner. 33716169 10 46 theme glycosylation 1923:1935 arg1 targets 1937:1943 previously characterized glycosylation targets 1898:1943 previously characterized glycosylation targets that contain varied domain architecture and function 1898:1996 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 46 theme glycosylation 1923:1935 arg1 them 1889:1892 them 1889:1892 them 1889:1892 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 46 theme glycosylation 1923:1935 arg1 % 1884:1884 64% 1882:1884 64% of them 1882:1892 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 3 47 theme target 564:569 arg1 proteins 571:578 target proteins 564:578 target proteins 564:578 It remains unclear how just two enzymes can be specifically controlled to affect glycosylation of target proteins and signaling pathways both basally and in response to stress. 33716169 1 48 theme proteins 187:194 arg1 proteins 187:194 intracellular proteins 173:194 intracellular proteins 173:194 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 1 48 theme proteins 187:194 arg1 residues 161:168 specific serine and threonine residues 131:168 specific serine and threonine residues of intracellular proteins 131:194 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 9 49 theme parallel 1674:1681 arg1 monitoring 1692:1701 parallel reaction monitoring 1674:1701 parallel reaction monitoring 1674:1701 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 4 50 theme evidence 660:667 arg1 lines 651:655 Several lines 643:655 Several lines of evidence 643:667 Several lines of evidence suggest that protein interactors regulate these responses by affecting OGT and O-GlcNAcase activity, localization, and substrate specificity. 33716169 1 51 theme O-linked 199:206 arg1 N-acetyl-β-D-glucosamine 208:231 O-linked N-acetyl-β-D-glucosamine 199:231 O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) 199:242 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 1 51 theme O-linked 199:206 arg1 O-GlcNAc 234:241 O-GlcNAc 234:241 O-GlcNAc 234:241 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 2 52 theme O-GlcNAc 324:331 arg1 enzymes 384:390 the sole enzymes 375:390 the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates 375:463 The O-GlcNAc transferase (OGT) and the O-GlcNAcase are the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates. 33716169 2 52 theme O-GlcNAc 324:331 arg1 OGT 346:348 OGT 346:348 OGT 346:348 The O-GlcNAc transferase (OGT) and the O-GlcNAcase are the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates. 33716169 2 52 theme O-GlcNAc 324:331 arg1 O-GlcNAcase 359:369 the O-GlcNAcase 355:369 the O-GlcNAcase 355:369 The O-GlcNAc transferase (OGT) and the O-GlcNAcase are the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates. 33716169 2 52 theme O-GlcNAc 324:331 arg1 transferase 333:343 The O-GlcNAc transferase 320:343 The O-GlcNAc transferase (OGT) 320:349 The O-GlcNAc transferase (OGT) and the O-GlcNAcase are the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates. 33716169 8 53 theme OGT 1411:1413 arg1 cleavage 1415:1422 the major OGT cleavage and glycosylation substrate 1401:1450 cleavage 1415:1422 These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation after stress. 33716169 8 53 theme OGT 1411:1413 arg1 factor 1463:1468 host cell factor 1 1453:1470 host cell factor 1 1453:1470 These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation after stress. 33716169 5 54 theme quantitative 900:911 arg1 proteomics 913:922 quantitative proteomics 900:922 quantitative proteomics 900:922 To provide insight into the mechanisms by which OGT function is controlled, we have used quantitative proteomics to define OGT's basal and stress-induced interactomes. 33716169 6 55 dep lysine 1163:1168 arg1 labeling 1200:1207 stable isotopic labeling 1184:1207 stable isotopic labeling of amino acids in cell culture 1184:1238 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 10 56 theme varied 1958:1963 arg1 architecture 1972:1983 varied domain architecture 1958:1983 varied domain architecture 1958:1983 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 3 57 theme pathways 594:601 arg1 glycosylation 547:559 glycosylation 547:559 glycosylation of target proteins and signaling pathways 547:601 It remains unclear how just two enzymes can be specifically controlled to affect glycosylation of target proteins and signaling pathways both basally and in response to stress. 33716169 1 58 theme dynamic 107:113 arg1 modification 115:126 The dynamic modification 103:126 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) 103:242 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 6 59 theme amino 1212:1216 arg1 acids 1218:1222 amino acids 1212:1222 amino acids in cell culture 1212:1238 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 6 60 from acids 1218:1222 arg1 culture 1232:1238 cell culture 1227:1238 cell culture 1227:1238 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 6 61 theme WT 1045:1046 arg1 lysates 1090:1096 OGT WT, null, and hydrogen peroxide-treated cell lysates 1041:1096 OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture) 1041:1239 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 9 62 theme stable 1744:1749 arg1 labeling 1760:1767 our discovery-based stable isotopic labeling 1724:1767 our discovery-based stable isotopic labeling of amino acids 1724:1782 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 8 63 theme host 1453:1456 arg1 cleavage 1415:1422 the major OGT cleavage and glycosylation substrate 1401:1450 cleavage 1415:1422 These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation after stress. 33716169 8 63 theme host 1453:1456 arg1 factor 1463:1468 host cell factor 1 1453:1470 host cell factor 1 1453:1470 These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation after stress. 33716169 3 64 gly glycosylation 547:559 arg1 pathways 594:601 signaling pathways 584:601 signaling pathways 584:601 It remains unclear how just two enzymes can be specifically controlled to affect glycosylation of target proteins and signaling pathways both basally and in response to stress. 33716169 3 64 gly glycosylation 547:559 arg1 proteins 571:578 target proteins 564:578 target proteins 564:578 It remains unclear how just two enzymes can be specifically controlled to affect glycosylation of target proteins and signaling pathways both basally and in response to stress. 33716169 6 65 from labeling 1200:1207 arg1 culture 1232:1238 cell culture 1227:1238 cell culture 1227:1238 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 1 66 theme serine 140:145 arg1 proteins 187:194 intracellular proteins 173:194 intracellular proteins 173:194 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 1 66 theme serine 140:145 arg1 residues 161:168 specific serine and threonine residues 131:168 specific serine and threonine residues of intracellular proteins 131:194 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 6 67 theme stable 1184:1189 arg1 labeling 1200:1207 stable isotopic labeling 1184:1207 stable isotopic labeling of amino acids in cell culture 1184:1238 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 1 68 theme threonine 151:159 arg1 proteins 187:194 intracellular proteins 173:194 intracellular proteins 173:194 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 1 68 theme threonine 151:159 arg1 residues 161:168 specific serine and threonine residues 131:168 specific serine and threonine residues of intracellular proteins 131:194 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 9 69 theme amino 1772:1776 arg1 acids 1778:1782 amino acids 1772:1782 amino acids 1772:1782 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 7 70 theme peroxide 1361:1368 arg1 stress 1370:1375 hydrogen peroxide stress 1352:1375 hydrogen peroxide stress 1352:1375 In total, more than 130 proteins were found to interact with OGT, many of which change their association upon hydrogen peroxide stress. 33716169 6 71 theme interaction 991:1001 arg1 partners 1003:1010 its interaction partners 987:1010 its interaction partners 987:1010 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 9 72 theme culture 1792:1798 arg1 approach 1800:1807 cell culture approach 1787:1807 cell culture approach 1787:1807 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 8 73 theme time-dependent 1494:1507 arg1 dissociation 1509:1520 a time-dependent dissociation 1492:1520 a time-dependent dissociation 1492:1520 These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation after stress. 33716169 6 74 theme peroxide-treated 1068:1083 arg1 lysates 1090:1096 OGT WT, null, and hydrogen peroxide-treated cell lysates 1041:1096 OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture) 1041:1239 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 4 75 theme OGT 740:742 arg1 activity 760:767 OGT and O-GlcNAcase activity 740:767 OGT and O-GlcNAcase activity 740:767 Several lines of evidence suggest that protein interactors regulate these responses by affecting OGT and O-GlcNAcase activity, localization, and substrate specificity. 33716169 2 76 theme sole 379:382 arg1 O-GlcNAcase 359:369 the O-GlcNAcase 355:369 the O-GlcNAcase 355:369 The O-GlcNAc transferase (OGT) and the O-GlcNAcase are the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates. 33716169 2 76 theme sole 379:382 arg1 enzymes 384:390 the sole enzymes 375:390 the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates 375:463 The O-GlcNAc transferase (OGT) and the O-GlcNAcase are the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates. 33716169 2 76 theme sole 379:382 arg1 transferase 333:343 The O-GlcNAc transferase 320:343 The O-GlcNAc transferase (OGT) 320:349 The O-GlcNAc transferase (OGT) and the O-GlcNAcase are the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates. 33716169 4 77 theme O-GlcNAcase 748:758 arg1 activity 760:767 OGT and O-GlcNAcase activity 740:767 OGT and O-GlcNAcase activity 740:767 Several lines of evidence suggest that protein interactors regulate these responses by affecting OGT and O-GlcNAcase activity, localization, and substrate specificity. 33716169 0 78 theme OGT 41:43 arg1 Interactome 45:55 the OGT Interactome 37:55 the OGT Interactome 37:55 Quantitative Proteomics Reveals that the OGT Interactome Is Remodeled in Response to Oxidative Stress. 33716169 1 79 theme models 312:317 arg1 variety 294:300 a variety 292:300 a variety of stress models 292:317 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 1 79 theme models 312:317 arg1 models 312:317 stress models 305:317 stress models 305:317 The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. 33716169 6 80 theme null 1049:1052 arg1 lysates 1090:1096 OGT WT, null, and hydrogen peroxide-treated cell lysates 1041:1096 OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture) 1041:1239 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 10 81 theme novel 1859:1863 arg1 interactors 1869:1879 novel OGT interactors 1859:1879 novel OGT interactors 1859:1879 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 81 theme novel 1859:1863 arg1 majority 1823:1830 the majority 1819:1830 the majority of proteins identified 1819:1853 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 9 82 theme glyceraldehyde 1593:1606 arg1 dehydrogenase 1620:1632 glyceraldehyde 3-phosphate dehydrogenase 1593:1632 glyceraldehyde 3-phosphate dehydrogenase 1593:1632 To validate less well-characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based stable isotopic labeling of amino acids in cell culture approach. 33716169 4 83 theme substrate 788:796 arg1 specificity 798:808 substrate specificity 788:808 substrate specificity 788:808 Several lines of evidence suggest that protein interactors regulate these responses by affecting OGT and O-GlcNAcase activity, localization, and substrate specificity. 33716169 6 84 theme cell 1085:1088 arg1 lysates 1090:1096 OGT WT, null, and hydrogen peroxide-treated cell lysates 1041:1096 OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture) 1041:1239 OGT and its interaction partners were immunoprecipitated from OGT WT, null, and hydrogen peroxide-treated cell lysates that had been isotopically labeled with light, medium, and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture). 33716169 10 85 theme characterized 1909:1921 arg1 targets 1937:1943 previously characterized glycosylation targets 1898:1943 previously characterized glycosylation targets that contain varied domain architecture and function 1898:1996 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 85 theme characterized 1909:1921 arg1 them 1889:1892 them 1889:1892 them 1889:1892 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 33716169 10 85 theme characterized 1909:1921 arg1 % 1884:1884 64% 1882:1884 64% of them 1882:1892 Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. 37015946 9 0 theme inadequate 1506:1515 arg1 resources 1524:1532 inadequate health resources 1506:1532 inadequate health resources 1506:1532 For a continent with inadequate health resources and where social distancing is unsustainable, vaccination is the best option. 37015946 6 1 theme Uganda 1031:1036 arg1 strains 1061:1067 Uganda influenza type-A virus strains 1031:1067 Uganda influenza type-A virus strains sequenced before 2016 1031:1089 Uganda influenza type-A virus strains sequenced before 2016 clustered uniquely while later strains mixed with other Africa and global strains. 37015946 5 2 dep binding 988:994 arg1 receptor 979:986 several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites 938:1028 receptor 979:986 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 9 3 theme where social 1538:1549 arg1 distancing 1551:1560 where social distancing 1538:1560 where social distancing 1538:1560 For a continent with inadequate health resources and where social distancing is unsustainable, vaccination is the best option. 37015946 3 4 theme swabs 505:509 arg1 215/234 489:495 215/234 489:495 215/234 489:495 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 3 4 theme swabs 505:509 arg1 % 486:486 92% 484:486 92% (215/234) of the swabs 484:509 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 3 4 theme swabs 505:509 arg1 swabs 505:509 the swabs 501:509 the swabs 501:509 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 1 5 theme viruses 195:201 arg1 characterisation 153:168 Genetic characterisation 145:168 Genetic characterisation of circulating influenza viruses 145:201 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. 37015946 10 6 theme genome 1666:1671 arg1 sequencing 1673:1682 routine genome sequencing 1658:1682 routine genome sequencing 1658:1682 Hence, African stakeholders should prioritise routine genome sequencing and analysis to direct vaccine selection and virus control. 37015946 9 7 theme health 1517:1522 arg1 resources 1524:1532 inadequate health resources 1506:1532 inadequate health resources 1506:1532 For a continent with inadequate health resources and where social distancing is unsustainable, vaccination is the best option. 37015946 0 8 theme other 123:127 arg1 strains 136:142 other Africa strains 123:142 other Africa strains 123:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 2 9 theme whole 334:338 arg1 genomes 340:346 whole genomes 334:346 whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018 334:453 We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. 37015946 1 10 theme strain 226:231 arg1 selection 233:241 annual vaccine strain selection 211:241 annual vaccine strain selection 211:241 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. 37015946 5 11 theme glycosylation 1010:1022 arg1 sites 1024:1028 several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites 938:1028 sites 1024:1028 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 3 12 theme whole 540:544 arg1 genomes 546:552 whole genomes 540:552 whole genomes 540:552 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 9 13 theme best 1599:1602 arg1 option 1604:1609 the best option 1595:1609 the best option 1595:1609 For a continent with inadequate health resources and where social distancing is unsustainable, vaccination is the best option. 37015946 9 13 theme best 1599:1602 arg1 vaccination 1580:1590 vaccination 1580:1590 vaccination 1580:1590 For a continent with inadequate health resources and where social distancing is unsustainable, vaccination is the best option. 37015946 0 14 from vaccines 110:117 arg1 strains 77:83 Uganda influenza type-A strains 53:83 Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains 53:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 0 14 from vaccines 110:117 arg1 variation 40:48 a 9-year variation 31:48 a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains 31:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 6 15 theme global 1158:1163 arg1 strains 1165:1171 global strains 1158:1171 global strains 1158:1171 Uganda influenza type-A virus strains sequenced before 2016 clustered uniquely while later strains mixed with other Africa and global strains. 37015946 5 16 theme % 861:861 arg1 similarity 874:883 95.46-100% amino acid similarity 852:883 95.46-100% amino acid similarity to the 2010-2020 season vaccines 852:916 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 0 17 theme influenza 60:68 arg1 strains 77:83 Uganda influenza type-A strains 53:83 Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains 53:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 10 18 theme vaccine 1707:1713 arg1 selection 1715:1723 direct vaccine selection 1700:1723 direct vaccine selection 1700:1723 Hence, African stakeholders should prioritise routine genome sequencing and analysis to direct vaccine selection and virus control. 37015946 4 19 theme Africa 674:679 arg1 strains 681:687 other Africa strains 668:687 other Africa strains 668:687 The newly-generated sequences were genetically and phylogenetically compared to the WHO-recommended vaccines and other Africa strains sampled since 1994. 37015946 0 20 theme strains 77:83 arg1 variation 40:48 a 9-year variation 31:48 a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains 31:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 1 21 theme circulating 173:183 arg1 viruses 195:201 circulating influenza viruses 173:201 circulating influenza viruses 173:201 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. 37015946 5 22 contain had 816:818 arg2 % 831:831 95.23-99.65% 820:831 95.23-99.65% 820:831 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 22 contain had 816:818 arg2 % 845:845 95.31-99.79% 834:845 95.31-99.79% 834:845 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 22 contain had 816:818 arg1 n = 206 738:744 n = 206 738:744 n = 206 738:744 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 22 contain had 816:818 arg2 similarity 874:883 95.46-100% amino acid similarity 852:883 95.46-100% amino acid similarity to the 2010-2020 season vaccines 852:916 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 22 contain had 816:818 arg1 protein 784:790 matrix protein 777:790 matrix protein (MP, n = 213) 777:804 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 22 contain had 816:818 arg1 neuraminidase 748:760 neuraminidase (n = 207) 748:770 neuraminidase (n = 207) 748:770 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 22 contain had 816:818 arg1 hemagglutinin 723:735 Uganda strain hemagglutinin 709:735 Uganda strain hemagglutinin (n = 206) 709:745 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 22 contain had 816:818 arg2 binding 988:994 several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites 938:1028 binding 988:994 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 23 theme Uganda 709:714 arg1 n = 206 738:744 n = 206 738:744 n = 206 738:744 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 23 theme Uganda 709:714 arg1 hemagglutinin 723:735 Uganda strain hemagglutinin 709:735 Uganda strain hemagglutinin (n = 206) 709:745 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 8 24 theme influenza 1378:1386 arg1 ecology 1388:1394 the global influenza ecology 1367:1394 the global influenza ecology 1367:1394 Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. 37015946 2 25 theme positive 386:393 arg1 swabs 403:407 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs 353:407 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018 353:453 We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. 37015946 4 26 dep WHO-recommended vaccines 639:662 arg1 the 635:637 the 635:637 the 635:637 The newly-generated sequences were genetically and phylogenetically compared to the WHO-recommended vaccines and other Africa strains sampled since 1994. 37015946 0 27 theme Phylogenomic 0:11 arg1 analysis 13:20 Phylogenomic analysis 0:20 Phylogenomic analysis 0:20 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 5 28 theme acid 869:872 arg1 similarity 874:883 95.46-100% amino acid similarity 852:883 95.46-100% amino acid similarity to the 2010-2020 season vaccines 852:916 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 8 29 theme viral 1406:1410 arg1 diversity 1420:1428 high viral genetic diversity 1401:1428 high viral genetic diversity 1401:1428 Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. 37015946 0 30 theme 9-year 33:38 arg1 variation 40:48 a 9-year variation 31:48 a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains 31:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 5 31 theme mutated 946:952 arg1 binding 988:994 several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites 938:1028 binding 988:994 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 8 32 theme progressive 1431:1441 arg1 drift 1453:1457 progressive antigenic drift 1431:1457 progressive antigenic drift 1431:1457 Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. 37015946 10 33 theme virus 1729:1733 arg1 control 1735:1741 virus control 1729:1741 virus control 1729:1741 Hence, African stakeholders should prioritise routine genome sequencing and analysis to direct vaccine selection and virus control. 37015946 5 34 theme antigenic 968:976 arg1 binding 988:994 several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites 938:1028 binding 988:994 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 7 35 dep 6B.1A.5 1239:1245 arg1 b 1249:1249 b 1249:1249 b 1249:1249 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 35 dep 6B.1A.5 1239:1245 arg1 a 1247:1247 a 1247:1247 a 1247:1247 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 3 36 theme sequences 469:477 arg1 sequences 469:477 sequences 469:477 sequences 469:477 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 3 36 theme sequences 469:477 arg1 193/215 517:523 193/215 517:523 193/215 517:523 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 3 36 theme sequences 469:477 arg1 % 514:514 90% 512:514 90% (193/215) 512:524 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 2 37 from swabs 403:407 arg1 genomes 340:346 whole genomes 334:346 whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018 334:453 We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. 37015946 7 38 theme A 1207:1207 arg1 subclades 1220:1228 novel A(H1N1)pdm09 subclades 1201:1228 novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019 1201:1343 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 38 theme A 1207:1207 arg1 6B.1A.5 1239:1245 6B.1A.5 1239:1245 6B.1A.5 1239:1245 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 38 theme A 1207:1207 arg1 6B.1A.3 1230:1236 6B.1A.3 1230:1236 6B.1A.3 1230:1236 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 38 theme A 1207:1207 arg1 6B.1A.6 1257:1263 6B.1A.6 1257:1263 6B.1A.6 1257:1263 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 0 39 from strains 136:142 arg1 strains 77:83 Uganda influenza type-A strains 53:83 Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains 53:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 0 39 from strains 136:142 arg1 variation 40:48 a 9-year variation 31:48 a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains 31:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 9 40 with continent 1491:1499 arg1 resources 1524:1532 inadequate health resources 1506:1532 inadequate health resources 1506:1532 For a continent with inadequate health resources and where social distancing is unsustainable, vaccination is the best option. 37015946 9 40 with continent 1491:1499 arg1 distancing 1551:1560 where social distancing 1538:1560 where social distancing 1538:1560 For a continent with inadequate health resources and where social distancing is unsustainable, vaccination is the best option. 37015946 2 41 theme A 378:378 arg1 swabs 403:407 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs 353:407 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018 353:453 We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. 37015946 1 42 theme infection 261:269 arg1 spread 271:276 infection spread 261:276 infection spread 261:276 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. 37015946 6 43 theme influenza 1038:1046 arg1 strains 1061:1067 Uganda influenza type-A virus strains 1031:1067 Uganda influenza type-A virus strains sequenced before 2016 1031:1089 Uganda influenza type-A virus strains sequenced before 2016 clustered uniquely while later strains mixed with other Africa and global strains. 37015946 5 44 dep protein 784:790 arg1 n = 213 797:803 n = 213 797:803 n = 213 797:803 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 44 dep protein 784:790 arg1 MP 793:794 MP 793:794 MP 793:794 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 10 45 theme African 1619:1625 arg1 stakeholders 1627:1638 African stakeholders 1619:1638 African stakeholders 1619:1638 Hence, African stakeholders should prioritise routine genome sequencing and analysis to direct vaccine selection and virus control. 37015946 1 46 theme influenza 185:193 arg1 viruses 195:201 circulating influenza viruses 173:201 circulating influenza viruses 173:201 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. 37015946 6 47 theme later 1116:1120 arg1 strains 1122:1128 later strains 1116:1128 later strains mixed with other Africa and global strains 1116:1171 Uganda influenza type-A virus strains sequenced before 2016 clustered uniquely while later strains mixed with other Africa and global strains. 37015946 2 48 used used 282:285 arg2 We 279:280 We 279:280 We 279:280 We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. 37015946 0 49 theme Africa 129:134 arg1 strains 136:142 other Africa strains 123:142 other Africa strains 123:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 3 50 from % 486:486 arg1 sequences 469:477 sequences 469:477 sequences 469:477 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 3 50 from % 486:486 arg1 193/215 517:523 193/215 517:523 193/215 517:523 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 3 50 from % 486:486 arg1 % 514:514 90% 512:514 90% (193/215) 512:524 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 10 51 theme routine 1658:1664 arg1 sequencing 1673:1682 routine genome sequencing 1658:1682 routine genome sequencing 1658:1682 Hence, African stakeholders should prioritise routine genome sequencing and analysis to direct vaccine selection and virus control. 37015946 1 52 theme vaccine 218:224 arg1 selection 233:241 annual vaccine strain selection 211:241 annual vaccine strain selection 211:241 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. 37015946 5 53 theme N-linked 1001:1008 arg1 sites 1024:1028 several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites 938:1028 sites 1024:1028 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 10 54 theme direct 1700:1705 arg1 selection 1715:1723 direct vaccine selection 1700:1723 direct vaccine selection 1700:1723 Hence, African stakeholders should prioritise routine genome sequencing and analysis to direct vaccine selection and virus control. 37015946 1 55 theme annual 211:216 arg1 selection 233:241 annual vaccine strain selection 211:241 annual vaccine strain selection 211:241 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. 37015946 5 56 dep hemagglutinin 723:735 arg1 sequences 806:814 sequences 806:814 sequences 806:814 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 3 57 from % 514:514 arg1 215/234 489:495 215/234 489:495 215/234 489:495 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 3 57 from % 514:514 arg1 % 486:486 92% 484:486 92% (215/234) of the swabs 484:509 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 3 57 from % 514:514 arg1 swabs 505:509 the swabs 501:509 the swabs 501:509 We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. 37015946 2 58 theme next-generation 287:301 arg1 sequencing 303:312 next-generation sequencing 287:312 next-generation sequencing 287:312 We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. 37015946 5 59 theme 95.46-100 852:860 arg1 % 861:861 % 861:861 % 861:861 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 0 60 theme type-A 70:75 arg1 strains 77:83 Uganda influenza type-A strains 53:83 Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains 53:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 1 61 theme Genetic 145:151 arg1 characterisation 153:168 Genetic characterisation 145:168 Genetic characterisation of circulating influenza viruses 145:201 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. 37015946 8 62 theme global 1371:1376 arg1 ecology 1388:1394 the global influenza ecology 1367:1394 the global influenza ecology 1367:1394 Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. 37015946 4 63 theme other 668:672 arg1 strains 681:687 other Africa strains 668:687 other Africa strains 668:687 The newly-generated sequences were genetically and phylogenetically compared to the WHO-recommended vaccines and other Africa strains sampled since 1994. 37015946 0 64 theme WHO-recommended 94:108 arg1 vaccines 110:117 the WHO-recommended vaccines 90:117 the WHO-recommended vaccines 90:117 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 5 65 link N-linked 1001:1008 arg1 sites 1024:1028 several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites 938:1028 sites 1024:1028 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 8 66 theme ecology 1388:1394 arg1 part 1359:1362 part 1359:1362 part of the global influenza ecology 1359:1394 Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. 37015946 6 67 theme virus 1055:1059 arg1 strains 1061:1067 Uganda influenza type-A virus strains 1031:1067 Uganda influenza type-A virus strains sequenced before 2016 1031:1089 Uganda influenza type-A virus strains sequenced before 2016 clustered uniquely while later strains mixed with other Africa and global strains. 37015946 5 68 theme strain 716:721 arg1 n = 206 738:744 n = 206 738:744 n = 206 738:744 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 68 theme strain 716:721 arg1 hemagglutinin 723:735 Uganda strain hemagglutinin 709:735 Uganda strain hemagglutinin (n = 206) 709:745 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 69 theme season 902:907 arg1 vaccines 909:916 the 2010-2020 season vaccines 888:916 the 2010-2020 season vaccines 888:916 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 0 70 from variation 40:48 arg1 strains 136:142 other Africa strains 123:142 other Africa strains 123:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 0 70 from variation 40:48 arg1 vaccines 110:117 the WHO-recommended vaccines 90:117 the WHO-recommended vaccines 90:117 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 5 71 theme amino 863:867 arg1 similarity 874:883 95.46-100% amino acid similarity 852:883 95.46-100% amino acid similarity to the 2010-2020 season vaccines 852:916 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 8 72 theme genetic 1412:1418 arg1 diversity 1420:1428 high viral genetic diversity 1401:1428 high viral genetic diversity 1401:1428 Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. 37015946 5 73 theme matrix 777:782 arg1 protein 784:790 matrix protein 777:790 matrix protein (MP, n = 213) 777:804 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 5 74 theme several 938:944 arg1 binding 988:994 several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites 938:1028 binding 988:994 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 8 75 theme antigenic 1443:1451 arg1 drift 1453:1457 progressive antigenic drift 1431:1457 progressive antigenic drift 1431:1457 Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. 37015946 2 76 theme patient 395:401 arg1 swabs 403:407 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs 353:407 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018 353:453 We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. 37015946 0 77 theme Uganda 53:58 arg1 strains 77:83 Uganda influenza type-A strains 53:83 Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains 53:142 Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains. 37015946 5 78 theme hemagglutinin 954:966 arg1 binding 988:994 several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites 938:1028 binding 988:994 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 8 79 theme high 1401:1404 arg1 diversity 1420:1428 high viral genetic diversity 1401:1428 high viral genetic diversity 1401:1428 Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. 37015946 7 80 theme novel 1201:1205 arg1 subclades 1220:1228 novel A(H1N1)pdm09 subclades 1201:1228 novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019 1201:1343 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 80 theme novel 1201:1205 arg1 6B.1A.5 1239:1245 6B.1A.5 1239:1245 6B.1A.5 1239:1245 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 80 theme novel 1201:1205 arg1 6B.1A.3 1230:1236 6B.1A.3 1230:1236 6B.1A.3 1230:1236 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 80 theme novel 1201:1205 arg1 6B.1A.6 1257:1263 6B.1A.6 1257:1263 6B.1A.6 1257:1263 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 8 81 theme local 1464:1468 arg1 transmissions 1470:1482 local transmissions 1464:1482 local transmissions 1464:1482 Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. 37015946 2 82 theme A 357:357 arg1 swabs 403:407 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs 353:407 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018 353:453 We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. 37015946 7 83 dep subclades 1220:1228 arg1 subclades 1220:1228 novel A(H1N1)pdm09 subclades 1201:1228 novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019 1201:1343 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 83 dep subclades 1220:1228 arg1 6B.1A.5 1239:1245 6B.1A.5 1239:1245 6B.1A.5 1239:1245 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 83 dep subclades 1220:1228 arg1 6B.1A.3 1230:1236 6B.1A.3 1230:1236 6B.1A.3 1230:1236 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 83 dep subclades 1220:1228 arg1 ± T120A 1266:1272 ± T120A 1266:1272 ± T120A 1266:1272 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 7 83 dep subclades 1220:1228 arg1 6B.1A.6 1257:1263 6B.1A.6 1257:1263 6B.1A.6 1257:1263 We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. 37015946 6 84 theme type-A 1048:1053 arg1 strains 1061:1067 Uganda influenza type-A virus strains 1031:1067 Uganda influenza type-A virus strains sequenced before 2016 1031:1089 Uganda influenza type-A virus strains sequenced before 2016 clustered uniquely while later strains mixed with other Africa and global strains. 37015946 5 85 gly glycosylation 1010:1022 arg2 sites 1024:1028 several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites 938:1028 sites 1024:1028 Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. 37015946 4 86 theme newly-generated 559:573 arg1 sequences 575:583 The newly-generated sequences 555:583 The newly-generated sequences 555:583 The newly-generated sequences were genetically and phylogenetically compared to the WHO-recommended vaccines and other Africa strains sampled since 1994. 37015946 2 87 theme 118 374:376 arg1 H3N2 380:383 H3N2 380:383 H3N2 380:383 We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. 37015946 2 87 theme 118 374:376 arg1 A 378:378 118 A 374:378 118 A(H3N2) 374:384 We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. 37015946 1 88 theme spread 271:276 arg1 mitigation 247:256 mitigation 247:256 mitigation of infection spread 247:276 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. 37015946 1 88 theme spread 271:276 arg1 selection 233:241 annual vaccine strain selection 211:241 annual vaccine strain selection 211:241 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. 34839261 9 0 gly N-glycosylation 1266:1280 arg2 three 1232:1236 three 1232:1236 three 1232:1236 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 9 0 gly N-glycosylation 1266:1280 arg2 sites 1282:1286 three distinct SARS-CoV-2 surface N-glycosylation sites 1232:1286 three distinct SARS-CoV-2 surface N-glycosylation sites 1232:1286 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 13 1 theme INTERPRETATION 1997:2010 arg1 results 2016:2022 INTERPRETATION Our results 1997:2022 INTERPRETATION Our results 1997:2022 INTERPRETATION Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. 34839261 5 2 theme Viral 697:701 arg1 entry 703:707 Viral entry 697:707 Viral entry 697:707 Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. 34839261 6 3 theme COVID-19 877:884 arg1 severity 886:893 COVID-19 severity 877:893 COVID-19 severity 877:893 Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. 34839261 12 4 theme vaccines 1921:1928 arg1 abilities 1896:1904 the neutralizing abilities 1879:1904 the neutralizing abilities of antibodies, vaccines, or convalescent sera 1879:1950 Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. 34839261 11 5 theme inhibiting 1571:1580 arg1 STT3A 1582:1586 inhibiting STT3A 1571:1586 inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) 1571:1635 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 10 6 theme COVID-19 1538:1545 arg1 severity 1547:1554 COVID-19 severity 1538:1554 COVID-19 severity 1538:1554 STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. 34839261 2 7 theme cells 320:324 arg1 machinery 302:310 the glycosylation machinery 284:310 the glycosylation machinery of host cells 284:324 Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. 34839261 13 8 theme SARS-CoV-2 2143:2152 arg1 infectivity 2162:2172 SARS-CoV-2 variant infectivity 2143:2172 SARS-CoV-2 variant infectivity 2143:2172 INTERPRETATION Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. 34839261 15 9 theme Acknowledgements 2384:2399 arg1 section 2401:2407 the Acknowledgements section 2380:2407 the Acknowledgements section 2380:2407 FUNDING A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. 34839261 8 10 theme anti-spike 1099:1108 arg1 antibody 1110:1117 non-neutralization anti-spike antibody 1080:1117 non-neutralization anti-spike antibody 1080:1117 We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. 34839261 7 11 theme NF-κB/STT3A-regulated 896:916 arg1 N-glycosylation 918:932 NF-κB/STT3A-regulated N-glycosylation 896:932 NF-κB/STT3A-regulated N-glycosylation 896:932 NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. 34839261 12 12 theme antibodies 1909:1918 arg1 abilities 1896:1904 the neutralizing abilities 1879:1904 the neutralizing abilities of antibodies, vaccines, or convalescent sera 1879:1950 Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. 34839261 9 13 theme binding 1213:1219 arg1 domain 1221:1226 The receptor binding domain 1200:1226 The receptor binding domain 1200:1226 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 1 14 with BACKGROUND 82:91 arg1 vaccines 134:141 anti-spike vaccines 123:141 anti-spike vaccines 123:141 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 1 14 with BACKGROUND 82:91 arg1 effectiveness 148:160 the effectiveness 144:160 the effectiveness of neutralizing antibodies 144:187 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 1 14 with BACKGROUND 82:91 arg1 vaccines 193:200 vaccines 193:200 vaccines 193:200 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 5 15 theme immunofluorescence 759:776 arg1 assays 778:783 luciferase, immunoblotting, and immunofluorescence assays 727:783 luciferase, immunoblotting, and immunofluorescence assays 727:783 Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. 34839261 1 16 theme SARS-CoV-2 244:253 arg1 variants 255:262 rapidly spreading SARS-CoV-2 variants 226:262 rapidly spreading SARS-CoV-2 variants 226:262 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 4 17 with binding 638:644 arg1 ACE2 691:694 ACE2 691:694 ACE2 691:694 METHODS We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. 34839261 13 18 theme profound 2123:2130 arg1 impacts 2132:2138 profound impacts 2123:2138 profound impacts 2123:2138 INTERPRETATION Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. 34839261 2 19 theme glycosylation 288:300 arg1 machinery 302:310 the glycosylation machinery 284:310 the glycosylation machinery of host cells 284:324 Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. 34839261 12 20 theme neutralizing 1883:1894 arg1 abilities 1896:1904 the neutralizing abilities 1879:1904 the neutralizing abilities of antibodies, vaccines, or convalescent sera 1879:1950 Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. 34839261 14 21 theme deglycosylation 2208:2222 arg1 method 2224:2229 a novel deglycosylation method 2200:2229 a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro 2200:2292 Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. 34839261 1 22 theme neutralizing 165:176 arg1 antibodies 178:187 neutralizing antibodies 165:187 neutralizing antibodies 165:187 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 12 23 theme spike 1844:1848 arg1 protein 1850:1856 spike protein 1844:1856 spike protein 1844:1856 Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. 34839261 8 24 theme non-neutralization 1080:1097 arg1 antibody 1110:1117 non-neutralization anti-spike antibody 1080:1117 non-neutralization anti-spike antibody 1080:1117 We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. 34839261 12 25 gly deglycosylate 1830:1842 arg1 protein 1850:1856 spike protein 1844:1856 spike protein 1844:1856 Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. 34839261 13 26 theme evolutionarily-conserved 2048:2071 arg1 glycosylation 2088:2100 targeting evolutionarily-conserved STT3A-mediated glycosylation 2038:2100 targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC 2038:2111 INTERPRETATION Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. 34839261 3 27 theme viral 472:476 arg1 protein 484:490 viral spike protein 472:490 viral spike protein 472:490 However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. 34839261 11 28 link N-linked 1594:1601 arg1 NGI-1 1630:1634 NGI-1 1630:1634 NGI-1 1630:1634 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 11 28 link N-linked 1594:1601 arg1 inhibitor-1 1617:1627 N-linked glycosylation inhibitor-1 1594:1627 N-linked glycosylation inhibitor-1 (NGI-1) 1594:1635 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 9 29 theme receptor 1204:1211 arg1 domain 1221:1226 The receptor binding domain 1200:1226 The receptor binding domain 1200:1226 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 0 30 theme Targeting 0:8 arg1 N-glycosylation 20:34 Targeting conserved N-glycosylation 0:34 Targeting conserved N-glycosylation 0:34 Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro. 34839261 8 31 theme SARS-CoV-2-infected 1164:1182 arg1 cells 1184:1188 SARS-CoV-2-infected cells 1164:1188 SARS-CoV-2-infected cells 1164:1188 We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. 34839261 14 32 theme novel 2202:2206 arg1 method 2224:2229 a novel deglycosylation method 2200:2229 a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro 2200:2292 Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. 34839261 11 33 dep variants 1685:1692 arg1 Beta 1715:1718 Beta (B.1.351) 1715:1728 Beta (B.1.351) 1715:1728 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 11 33 dep variants 1685:1692 arg1 [Alpha 1694:1699 [Alpha (B.1.1.7) 1694:1709 [Alpha (B.1.1.7) 1694:1709 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 11 33 dep variants 1685:1692 arg1 variants 1685:1692 its variants 1681:1692 its variants [Alpha (B.1.1.7) and Beta (B.1.351)] 1681:1729 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 1 34 theme anti-spike 123:132 arg1 vaccines 134:141 anti-spike vaccines 123:141 anti-spike vaccines 123:141 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 11 35 theme SARS-CoV-2 1646:1655 arg1 infectivity 1657:1667 SARS-CoV-2 infectivity 1646:1667 SARS-CoV-2 infectivity 1646:1667 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 0 36 theme SARS-CoV-2 43:52 arg1 infection 62:70 SARS-CoV-2 variant infection 43:70 SARS-CoV-2 variant infection 43:70 Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro. 34839261 10 37 theme spike 1484:1488 arg1 glycosylation 1490:1502 spike glycosylation 1484:1502 spike glycosylation 1484:1502 STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. 34839261 4 38 dep deglycosylated 665:678 arg1 spike 680:684 spike 680:684 spike 680:684 METHODS We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. 34839261 14 39 theme variant 2267:2273 arg1 infection 2275:2283 SARS-CoV-2 variant infection 2256:2283 SARS-CoV-2 variant infection 2256:2283 Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. 34839261 9 40 theme N-glycosylation 1266:1280 arg1 sites 1282:1286 three distinct SARS-CoV-2 surface N-glycosylation sites 1232:1286 three distinct SARS-CoV-2 surface N-glycosylation sites 1232:1286 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 15 41 theme funding 2318:2324 arg1 bodies 2326:2331 funding bodies 2318:2331 funding bodies that contributed to this study 2318:2362 FUNDING A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. 34839261 6 42 theme Genome-wide 786:796 arg1 association 798:808 Genome-wide association 786:808 Genome-wide association study (GWAS) 786:821 Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. 34839261 12 43 theme SARS-CoV-2 1965:1974 arg1 infectivity 1984:1994 SARS-CoV-2 variant infectivity 1965:1994 SARS-CoV-2 variant infectivity 1965:1994 Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. 34839261 4 44 theme glycosylated 649:660 arg1 binding 638:644 binding 638:644 binding of glycosylated or deglycosylated spike with ACE2 638:694 METHODS We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. 34839261 9 45 theme spike 1301:1305 arg1 proteins 1307:1314 57,311 spike proteins 1294:1314 57,311 spike proteins retrieved from the NCBI-Virus-database 1294:1353 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 3 46 theme variants 537:544 arg1 infectivity 503:513 infectivity 503:513 infectivity of SARS-CoV-2 and its variants 503:544 However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. 34839261 4 47 theme interferometry 602:615 arg1 approaches 617:626 BioLayer interferometry approaches 593:626 BioLayer interferometry approaches 593:626 METHODS We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. 34839261 13 48 theme variant 2154:2160 arg1 infectivity 2162:2172 SARS-CoV-2 variant infectivity 2143:2172 SARS-CoV-2 variant infectivity 2143:2172 INTERPRETATION Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. 34839261 9 49 theme SARS-CoV-2 1247:1256 arg1 sites 1282:1286 three distinct SARS-CoV-2 surface N-glycosylation sites 1232:1286 three distinct SARS-CoV-2 surface N-glycosylation sites 1232:1286 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 12 50 theme convalescent 1934:1945 arg1 sera 1947:1950 convalescent sera 1934:1950 convalescent sera 1934:1950 Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. 34839261 2 51 theme host 315:318 arg1 cells 320:324 host cells 315:324 host cells 315:324 Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. 34839261 7 52 theme gene 954:957 arg1 knockdown 959:967 gene knockdown 954:967 gene knockdown 954:967 NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. 34839261 6 53 theme significant 834:844 arg1 relationship 846:857 a significant relationship 832:857 a significant relationship between STT3A and COVID-19 severity 832:893 Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. 34839261 5 54 theme immunoblotting 739:752 arg1 assays 778:783 luciferase, immunoblotting, and immunofluorescence assays 727:783 luciferase, immunoblotting, and immunofluorescence assays 727:783 Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. 34839261 4 55 theme deglycosylated 665:678 arg1 binding 638:644 binding 638:644 binding of glycosylated or deglycosylated spike with ACE2 638:694 METHODS We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. 34839261 1 56 theme spreading 234:242 arg1 variants 255:262 rapidly spreading SARS-CoV-2 variants 226:262 rapidly spreading SARS-CoV-2 variants 226:262 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 5 57 theme luciferase 727:736 arg1 assays 778:783 luciferase, immunoblotting, and immunofluorescence assays 727:783 luciferase, immunoblotting, and immunofluorescence assays 727:783 Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. 34839261 9 58 theme ACE2 1420:1423 arg1 interaction 1425:1435 ACE2 interaction 1420:1435 ACE2 interaction 1420:1435 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 1 59 theme antibodies 178:187 arg1 vaccines 134:141 anti-spike vaccines 123:141 anti-spike vaccines 123:141 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 1 59 theme antibodies 178:187 arg1 effectiveness 148:160 the effectiveness 144:160 the effectiveness of neutralizing antibodies 144:187 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 1 59 theme antibodies 178:187 arg1 vaccines 193:200 vaccines 193:200 vaccines 193:200 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 3 60 from glycosylation 455:467 arg1 protein 484:490 viral spike protein 472:490 viral spike protein 472:490 However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. 34839261 11 61 theme N-linked 1594:1601 arg1 NGI-1 1630:1634 NGI-1 1630:1634 NGI-1 1630:1634 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 11 61 theme N-linked 1594:1601 arg1 inhibitor-1 1617:1627 N-linked glycosylation inhibitor-1 1594:1627 N-linked glycosylation inhibitor-1 (NGI-1) 1594:1635 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 13 62 theme targeting 2038:2046 arg1 glycosylation 2088:2100 targeting evolutionarily-conserved STT3A-mediated glycosylation 2038:2100 targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC 2038:2111 INTERPRETATION Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. 34839261 14 63 theme suitable 2231:2238 arg1 method 2224:2229 a novel deglycosylation method 2200:2229 a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro 2200:2292 Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. 34839261 13 64 theme STT3A-mediated 2073:2086 arg1 glycosylation 2088:2100 targeting evolutionarily-conserved STT3A-mediated glycosylation 2038:2100 targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC 2038:2111 INTERPRETATION Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. 34839261 3 65 theme spike 478:482 arg1 protein 484:490 viral spike protein 472:490 viral spike protein 472:490 However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. 34839261 0 66 theme conserved 10:18 arg1 N-glycosylation 20:34 Targeting conserved N-glycosylation 0:34 Targeting conserved N-glycosylation 0:34 Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro. 34839261 1 67 theme clinical 101:108 arg1 success 110:116 clinical success 101:116 clinical success 101:116 BACKGROUND Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. 34839261 10 68 theme key 1449:1451 arg1 glycosyltransferase 1453:1471 a key glycosyltransferase 1447:1471 a key glycosyltransferase catalyzing spike glycosylation 1447:1502 STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. 34839261 10 68 theme key 1449:1451 arg1 STT3A 1438:1442 STT3A 1438:1442 STT3A 1438:1442 STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. 34839261 12 69 theme SARS-CoV-2-infected 1766:1784 arg1 cells 1786:1790 SARS-CoV-2-infected cells 1766:1790 SARS-CoV-2-infected cells 1766:1790 Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. 34839261 8 70 theme antibody-drug 1037:1049 arg1 conjugate 1051:1059 an antibody-drug conjugate 1034:1059 an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells 1034:1188 We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. 34839261 8 70 theme antibody-drug 1037:1049 arg1 ADC 1062:1064 ADC 1062:1064 ADC 1062:1064 We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. 34839261 4 71 theme BioLayer 593:600 arg1 approaches 617:626 BioLayer interferometry approaches 593:626 BioLayer interferometry approaches 593:626 METHODS We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. 34839261 0 72 theme variant 54:60 arg1 infection 62:70 SARS-CoV-2 variant infection 43:70 SARS-CoV-2 variant infection 43:70 Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro. 34839261 11 73 theme glycosylation 1603:1615 arg1 NGI-1 1630:1634 NGI-1 1630:1634 NGI-1 1630:1634 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 11 73 theme glycosylation 1603:1615 arg1 inhibitor-1 1617:1627 N-linked glycosylation inhibitor-1 1594:1627 N-linked glycosylation inhibitor-1 (NGI-1) 1594:1635 We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. 34839261 3 74 theme targeting 445:453 arg1 glycosylation 455:467 targeting glycosylation 445:467 targeting glycosylation on viral spike protein 445:490 However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. 34839261 4 75 theme flow 566:569 arg1 cytometry 571:579 flow cytometry 566:579 flow cytometry 566:579 METHODS We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. 34839261 9 76 theme distinct 1238:1245 arg1 sites 1282:1286 three distinct SARS-CoV-2 surface N-glycosylation sites 1232:1286 three distinct SARS-CoV-2 surface N-glycosylation sites 1232:1286 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 4 77 dep METHODS 547:553 arg1 adopted 558:564 adopted 558:564 adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2 558:694 METHODS We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. 34839261 15 78 theme bodies 2326:2331 arg1 list 2310:2313 FUNDING A full list 2295:2313 FUNDING A full list of funding bodies that contributed to this study 2295:2362 FUNDING A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. 34839261 12 79 theme variant 1976:1982 arg1 infectivity 1984:1994 SARS-CoV-2 variant infectivity 1965:1994 SARS-CoV-2 variant infectivity 1965:1994 Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. 34839261 9 80 theme surface 1258:1264 arg1 sites 1282:1286 three distinct SARS-CoV-2 surface N-glycosylation sites 1232:1286 three distinct SARS-CoV-2 surface N-glycosylation sites 1232:1286 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 2 81 theme immune 363:368 arg1 response 370:377 the host's immune response 352:377 the host's immune response 352:377 Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. 34839261 7 82 theme promoter 1005:1012 arg1 assay 1014:1018 promoter assay 1005:1018 promoter assay 1005:1018 NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. 34839261 9 83 dep FINDINGS 1191:1198 arg1 domain 1221:1226 The receptor binding domain 1200:1226 The receptor binding domain 1200:1226 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 14 84 theme SARS-CoV-2 2256:2265 arg1 infection 2275:2283 SARS-CoV-2 variant infection 2256:2283 SARS-CoV-2 variant infection 2256:2283 Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. 34839261 6 85 theme association 798:808 arg1 GWAS 817:820 GWAS 817:820 GWAS 817:820 Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. 34839261 6 85 theme association 798:808 arg1 study 810:814 Genome-wide association study 786:814 Genome-wide association study (GWAS) 786:821 Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. 34839261 3 86 theme SARS-CoV-2 518:527 arg1 infectivity 503:513 infectivity 503:513 infectivity of SARS-CoV-2 and its variants 503:544 However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. 34839261 15 87 located found 2371:2375 arg1 section 2401:2407 the Acknowledgements section 2380:2407 the Acknowledgements section 2380:2407 FUNDING A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. 34839261 15 87 located found 2371:2375 arg2 list 2310:2313 FUNDING A full list 2295:2313 FUNDING A full list of funding bodies that contributed to this study 2295:2362 FUNDING A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. 34839261 15 88 theme full 2305:2308 arg1 list 2310:2313 FUNDING A full list 2295:2313 FUNDING A full list of funding bodies that contributed to this study 2295:2362 FUNDING A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. 34839261 12 89 theme sera 1947:1950 arg1 abilities 1896:1904 the neutralizing abilities 1879:1904 the neutralizing abilities of antibodies, vaccines, or convalescent sera 1879:1950 Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. 34839261 9 90 dep conserved 1381:1389 arg1 % 1397:1397 99.67% 1392:1397 99.67% 1392:1397 FINDINGS The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. 34839261 3 91 gly glycosylation 455:467 arg1 protein 484:490 viral spike protein 472:490 viral spike protein 472:490 However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. 34839261 2 92 theme antibody 393:400 arg1 efficiency 402:411 antibody efficiency 393:411 antibody efficiency 393:411 Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. 34839261 7 93 theme chromatin 970:978 arg1 immunoprecipitation 980:998 chromatin immunoprecipitation 970:998 chromatin immunoprecipitation 970:998 NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. 34086870 6 0 theme potential 1270:1278 arg1 treatment 1280:1288 potential treatment 1270:1288 potential treatment of infections 1270:1302 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 3 1 theme gene 514:517 arg1 therapy 519:525 gene therapy 514:525 an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter 494:716 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 1 2 theme described 260:268 arg1 disease 101:107 XMEN disease 96:107 XMEN disease 96:107 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 1 2 theme described 260:268 arg1 immunodeficiency 278:293 a recently described primary immunodeficiency 249:293 a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells 249:351 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 6 3 theme NK 1194:1195 arg1 NKG2D 1215:1219 NKG2D 1215:1219 NKG2D 1215:1219 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 6 3 theme NK 1194:1195 arg1 D 1212:1212 NK group 2 member D 1194:1212 NK group 2 member D (NKG2D) expression 1194:1231 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 4 4 theme progenitor 852:861 arg1 cells 863:867 low engraftable gene-edited hematopoietic stem and progenitor cells 801:867 cells 863:867 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 3 5 theme promoter 709:716 arg1 regulation 680:689 the regulation 676:689 the regulation of the endogenous promoter 676:716 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 6 6 theme clinical 1422:1429 arg1 translation 1431:1441 clinical translation 1422:1441 clinical translation 1422:1441 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 1 7 theme Epstein-Barr 181:192 arg1 virus 194:198 Epstein-Barr virus 181:198 Epstein-Barr virus infection 181:208 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 6 8 theme CD8+ 1172:1175 arg1 cells 1179:1183 human NK and CD8+ T cells 1159:1183 cells 1179:1183 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 5 9 dep efficient 1035:1043 arg1 % 1049:1049 >60% 1046:1049 >60% 1046:1049 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 1 10 gly glycosylation 223:235 arg1 deficiency 137:146 "X-linked MAGT1 deficiency 121:146 "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect 121:242 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 3 11 theme adeno-associated 579:594 arg1 AAV 604:606 AAV 604:606 AAV 604:606 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 3 11 theme adeno-associated 579:594 arg1 vector 596:601 a CRISPR/Cas9 adeno-associated vector 565:601 a CRISPR/Cas9 adeno-associated vector (AAV) 565:607 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 1 12 theme N-linked 214:221 arg1 glycosylation 223:235 N-linked glycosylation 214:235 N-linked glycosylation 214:235 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 6 13 theme D 1212:1212 arg1 expression 1222:1231 NK group 2 member D (NKG2D) expression 1194:1231 NK group 2 member D (NKG2D) expression 1194:1231 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 3 14 theme therapeutic 621:631 arg1 gene 639:642 a therapeutic MAGT1 gene 619:642 a therapeutic MAGT1 gene 619:642 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 1 15 theme MAGT1 131:135 arg1 deficiency 137:146 "X-linked MAGT1 deficiency 121:146 "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect 121:242 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 5 16 theme transient 914:922 arg1 enhancement 924:934 transient enhancement 914:934 transient enhancement of homology-directed repair 914:962 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 5 17 theme GE 897:898 arg1 conditions 900:909 GE conditions 897:909 GE conditions 897:909 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 5 18 theme transplanted 1099:1110 arg1 mice 1112:1115 transplanted mice 1099:1115 transplanted mice 1099:1115 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 5 19 theme AAV-associated 982:995 arg1 damage 1001:1006 AAV-associated DNA damage 982:1006 AAV-associated DNA damage response 982:1015 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 2 20 theme stem 406:409 arg1 transplantation 416:430 a potentially curative hematopoietic stem cell transplantation 369:430 a potentially curative hematopoietic stem cell transplantation 369:430 Unfortunately, a potentially curative hematopoietic stem cell transplantation is associated with high mortality rates. 34086870 6 21 theme long-term 1332:1340 arg1 therapy 1347:1353 long-term gene therapy 1332:1353 long-term gene therapy 1332:1353 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 5 22 theme damage 1001:1006 arg1 response 1008:1015 AAV-associated DNA damage response 982:1015 AAV-associated DNA damage response 982:1015 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 4 23 theme CRISPR/Cas9 743:753 arg1 GE 782:783 GE 782:783 GE 782:783 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 4 23 theme CRISPR/Cas9 743:753 arg1 editing 773:779 CRISPR/Cas9 AAV-targeted gene editing 743:779 CRISPR/Cas9 AAV-targeted gene editing (GE) 743:784 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 2 24 theme curative 383:390 arg1 transplantation 416:430 a potentially curative hematopoietic stem cell transplantation 369:430 a potentially curative hematopoietic stem cell transplantation 369:430 Unfortunately, a potentially curative hematopoietic stem cell transplantation is associated with high mortality rates. 34086870 0 25 theme CRISPR-targeted 0:14 arg1 insertion 22:30 CRISPR-targeted MAGT1 insertion 0:30 CRISPR-targeted MAGT1 insertion 0:30 CRISPR-targeted MAGT1 insertion restores XMEN patient hematopoietic stem cells and lymphocytes. 34086870 5 26 theme homology-directed 939:955 arg1 repair 957:962 homology-directed repair 939:962 homology-directed repair 939:962 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 2 27 theme high 451:454 arg1 rates 466:470 high mortality rates 451:470 high mortality rates 451:470 Unfortunately, a potentially curative hematopoietic stem cell transplantation is associated with high mortality rates. 34086870 4 28 theme gene 768:771 arg1 GE 782:783 GE 782:783 GE 782:783 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 4 28 theme gene 768:771 arg1 editing 773:779 CRISPR/Cas9 AAV-targeted gene editing 743:779 CRISPR/Cas9 AAV-targeted gene editing (GE) 743:784 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 1 29 theme defective 305:313 arg1 cells 317:321 defective T cells 305:321 defective T cells 305:321 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 4 30 theme gene-edited 817:827 arg1 HSPCs 870:874 HSPCs 870:874 HSPCs 870:874 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 4 30 theme gene-edited 817:827 arg1 stem 843:846 low engraftable gene-edited hematopoietic stem and progenitor cells 801:867 stem 843:846 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 0 31 theme XMEN 41:44 arg1 cells 73:77 XMEN patient hematopoietic stem cells 41:77 XMEN patient hematopoietic stem cells 41:77 CRISPR-targeted MAGT1 insertion restores XMEN patient hematopoietic stem cells and lymphocytes. 34086870 3 32 with patients 540:547 arg1 XMEN 554:557 XMEN 554:557 XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter 554:716 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 1 33 link X-linked 122:129 arg1 deficiency 137:146 "X-linked MAGT1 deficiency 121:146 "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect 121:242 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 3 34 theme ex 497:498 arg1 approach 527:534 an ex vivo targeted gene therapy approach 494:534 an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter 494:716 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 6 35 theme therapeutic 1382:1392 arg1 options 1394:1400 2 efficient therapeutic options 1370:1400 2 efficient therapeutic options for XMEN poised for clinical translation 1370:1441 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 1 36 theme natural 327:333 arg1 NK 343:344 NK 343:344 NK 343:344 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 1 36 theme natural 327:333 arg1 killer 335:340 natural killer 327:340 natural killer (NK) cells 327:351 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 6 37 from function 1147:1154 arg1 cells 1179:1183 human NK and CD8+ T cells 1159:1183 cells 1179:1183 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 6 37 from function 1147:1154 arg1 NK 1165:1166 human NK and CD8+ T cells 1159:1183 NK 1165:1166 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 6 38 theme MAGT1 1127:1131 arg1 function 1147:1154 Restored MAGT1 glycosylation function 1118:1154 Restored MAGT1 glycosylation function in human NK and CD8+ T cells 1118:1183 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 4 39 theme low 801:803 arg1 HSPCs 870:874 HSPCs 870:874 HSPCs 870:874 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 4 39 theme low 801:803 arg1 stem 843:846 low engraftable gene-edited hematopoietic stem and progenitor cells 801:867 stem 843:846 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 3 40 theme therapy 519:525 arg1 approach 527:534 an ex vivo targeted gene therapy approach 494:534 an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter 494:716 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 3 41 theme endogenous 698:707 arg1 promoter 709:716 the endogenous promoter 694:716 the endogenous promoter 694:716 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 3 42 theme targeted 505:512 arg1 approach 527:534 an ex vivo targeted gene therapy approach 494:534 an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter 494:716 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 6 43 from function 1237:1244 arg1 lymphocytes 1254:1264 XMEN lymphocytes 1249:1264 XMEN lymphocytes 1249:1264 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 1 44 theme primary 270:276 arg1 disease 101:107 XMEN disease 96:107 XMEN disease 96:107 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 1 44 theme primary 270:276 arg1 immunodeficiency 278:293 a recently described primary immunodeficiency 249:293 a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells 249:351 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 6 45 theme XMEN 1249:1252 arg1 lymphocytes 1254:1264 XMEN lymphocytes 1249:1264 XMEN lymphocytes 1249:1264 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 0 46 theme hematopoietic 54:66 arg1 cells 73:77 XMEN patient hematopoietic stem cells 41:77 XMEN patient hematopoietic stem cells 41:77 CRISPR-targeted MAGT1 insertion restores XMEN patient hematopoietic stem cells and lymphocytes. 34086870 6 47 theme T 1177:1177 arg1 cells 1179:1183 human NK and CD8+ T cells 1159:1183 cells 1179:1183 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 3 48 theme CRISPR/Cas9 567:577 arg1 AAV 604:606 AAV 604:606 AAV 604:606 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 3 48 theme CRISPR/Cas9 567:577 arg1 vector 596:601 a CRISPR/Cas9 adeno-associated vector 565:601 a CRISPR/Cas9 adeno-associated vector (AAV) 565:607 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 1 49 theme virus 194:198 arg1 infection 200:208 Epstein-Barr virus infection 181:208 Epstein-Barr virus infection 181:208 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 6 50 theme human 1159:1163 arg1 NK 1165:1166 human NK and CD8+ T cells 1159:1183 NK 1165:1166 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 5 51 theme XMEN 1085:1088 arg1 HSPCs 1090:1094 XMEN HSPCs 1085:1094 XMEN HSPCs 1085:1094 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 6 52 theme infections 1293:1302 arg1 treatment 1280:1288 potential treatment 1270:1288 potential treatment of infections 1270:1302 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 5 53 theme genetic 1052:1058 arg1 correction 1060:1069 highly efficient (>60%) genetic correction 1028:1069 highly efficient (>60%) genetic correction 1028:1069 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 1 54 theme X-linked 122:129 arg1 deficiency 137:146 "X-linked MAGT1 deficiency 121:146 "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect 121:242 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 6 55 theme member 1205:1210 arg1 NKG2D 1215:1219 NKG2D 1215:1219 NKG2D 1215:1219 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 6 55 theme member 1205:1210 arg1 D 1212:1212 NK group 2 member D 1194:1212 NK group 2 member D (NKG2D) expression 1194:1231 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 4 56 theme Clinical 719:726 arg1 translation 728:738 Clinical translation 719:738 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) 719:784 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 6 57 from expression 1222:1231 arg1 lymphocytes 1254:1264 XMEN lymphocytes 1249:1264 XMEN lymphocytes 1249:1264 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 6 58 theme efficient 1372:1380 arg1 options 1394:1400 2 efficient therapeutic options 1370:1400 2 efficient therapeutic options for XMEN poised for clinical translation 1370:1441 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 6 59 theme group 1197:1201 arg1 NKG2D 1215:1219 NKG2D 1215:1219 NKG2D 1215:1219 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 6 59 theme group 1197:1201 arg1 D 1212:1212 NK group 2 member D 1194:1212 NK group 2 member D (NKG2D) expression 1194:1231 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 1 60 theme increased 153:161 arg1 susceptibility 163:176 increased susceptibility 153:176 increased susceptibility to Epstein-Barr virus infection 153:208 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 1 61 with deficiency 137:146 arg1 glycosylation 223:235 N-linked glycosylation 214:235 N-linked glycosylation 214:235 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 1 61 with deficiency 137:146 arg1 susceptibility 163:176 increased susceptibility 153:176 increased susceptibility to Epstein-Barr virus infection 153:208 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 1 62 link N-linked 214:221 arg1 glycosylation 223:235 N-linked glycosylation 214:235 N-linked glycosylation 214:235 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 4 63 theme editing 773:779 arg1 translation 728:738 Clinical translation 719:738 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) 719:784 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 6 64 theme gene 1342:1345 arg1 therapy 1347:1353 long-term gene therapy 1332:1353 long-term gene therapy 1332:1353 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 3 65 dep ex 497:498 arg1 vivo 500:503 vivo 500:503 vivo 500:503 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 2 66 theme hematopoietic 392:404 arg1 transplantation 416:430 a potentially curative hematopoietic stem cell transplantation 369:430 a potentially curative hematopoietic stem cell transplantation 369:430 Unfortunately, a potentially curative hematopoietic stem cell transplantation is associated with high mortality rates. 34086870 0 67 theme MAGT1 16:20 arg1 insertion 22:30 CRISPR-targeted MAGT1 insertion 0:30 CRISPR-targeted MAGT1 insertion 0:30 CRISPR-targeted MAGT1 insertion restores XMEN patient hematopoietic stem cells and lymphocytes. 34086870 1 68 theme XMEN 96:99 arg1 disease 101:107 XMEN disease 96:107 XMEN disease 96:107 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 1 68 theme XMEN 96:99 arg1 immunodeficiency 278:293 a recently described primary immunodeficiency 249:293 a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells 249:351 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 2 69 theme mortality 456:464 arg1 rates 466:470 high mortality rates 451:470 high mortality rates 451:470 Unfortunately, a potentially curative hematopoietic stem cell transplantation is associated with high mortality rates. 34086870 1 70 dep susceptibility 163:176 arg1 defect 237:242 defect 237:242 defect 237:242 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 5 71 theme repair 957:962 arg1 enhancement 924:934 transient enhancement 914:934 transient enhancement of homology-directed repair 914:962 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 5 72 theme DNA 997:999 arg1 damage 1001:1006 AAV-associated DNA damage 982:1006 AAV-associated DNA damage response 982:1015 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 4 73 theme AAV-targeted 755:766 arg1 GE 782:783 GE 782:783 GE 782:783 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 4 73 theme AAV-targeted 755:766 arg1 editing 773:779 CRISPR/Cas9 AAV-targeted gene editing 743:779 CRISPR/Cas9 AAV-targeted gene editing (GE) 743:784 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 0 74 theme patient 46:52 arg1 cells 73:77 XMEN patient hematopoietic stem cells 41:77 XMEN patient hematopoietic stem cells 41:77 CRISPR-targeted MAGT1 insertion restores XMEN patient hematopoietic stem cells and lymphocytes. 34086870 1 75 theme T 315:315 arg1 cells 317:321 defective T cells 305:321 defective T cells 305:321 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 5 76 theme efficient 1035:1043 arg1 correction 1060:1069 highly efficient (>60%) genetic correction 1028:1069 highly efficient (>60%) genetic correction 1028:1069 Here, we optimized GE conditions by transient enhancement of homology-directed repair while suppressing AAV-associated DNA damage response to achieve highly efficient (>60%) genetic correction in engrafting XMEN HSPCs in transplanted mice. 34086870 3 77 theme MAGT1 633:637 arg1 gene 639:642 a therapeutic MAGT1 gene 619:642 a therapeutic MAGT1 gene 619:642 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 4 78 theme engraftable 805:815 arg1 HSPCs 870:874 HSPCs 870:874 HSPCs 870:874 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 4 78 theme engraftable 805:815 arg1 stem 843:846 low engraftable gene-edited hematopoietic stem and progenitor cells 801:867 stem 843:846 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 2 79 theme cell 411:414 arg1 transplantation 416:430 a potentially curative hematopoietic stem cell transplantation 369:430 a potentially curative hematopoietic stem cell transplantation 369:430 Unfortunately, a potentially curative hematopoietic stem cell transplantation is associated with high mortality rates. 34086870 0 80 theme stem 68:71 arg1 cells 73:77 XMEN patient hematopoietic stem cells 41:77 XMEN patient hematopoietic stem cells 41:77 CRISPR-targeted MAGT1 insertion restores XMEN patient hematopoietic stem cells and lymphocytes. 34086870 4 81 theme hematopoietic 829:841 arg1 HSPCs 870:874 HSPCs 870:874 HSPCs 870:874 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 4 81 theme hematopoietic 829:841 arg1 stem 843:846 low engraftable gene-edited hematopoietic stem and progenitor cells 801:867 stem 843:846 Clinical translation of CRISPR/Cas9 AAV-targeted gene editing (GE) is hampered by low engraftable gene-edited hematopoietic stem and progenitor cells (HSPCs). 34086870 1 82 theme killer 335:340 arg1 cells 347:351 natural killer (NK) cells 327:351 natural killer (NK) cells 327:351 XMEN disease, defined as "X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect," is a recently described primary immunodeficiency marked by defective T cells and natural killer (NK) cells. 34086870 6 83 theme glycosylation 1133:1145 arg1 function 1147:1154 Restored MAGT1 glycosylation function 1118:1154 Restored MAGT1 glycosylation function in human NK and CD8+ T cells 1118:1183 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 3 84 theme constitutive 651:662 arg1 locus 664:668 the constitutive locus 647:668 the constitutive locus under the regulation of the endogenous promoter 647:716 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 34086870 6 85 theme Restored 1118:1125 arg1 function 1147:1154 Restored MAGT1 glycosylation function 1118:1154 Restored MAGT1 glycosylation function in human NK and CD8+ T cells 1118:1183 Restored MAGT1 glycosylation function in human NK and CD8+ T cells restored NK group 2 member D (NKG2D) expression and function in XMEN lymphocytes for potential treatment of infections, and it corrected HSPCs for long-term gene therapy, thus offering 2 efficient therapeutic options for XMEN poised for clinical translation. 34086870 3 86 from locus 664:668 arg1 insert 612:617 insert 612:617 insert 612:617 We sought to develop an ex vivo targeted gene therapy approach for patients with XMEN using a CRISPR/Cas9 adeno-associated vector (AAV) to insert a therapeutic MAGT1 gene at the constitutive locus under the regulation of the endogenous promoter. 37188790 5 0 theme mass 800:803 arg1 MS 819:820 MS 819:820 MS 819:820 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 5 0 theme mass 800:803 arg1 spectrometry 805:816 mass spectrometry 800:816 mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls) 800:882 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 4 1 theme expressed 530:538 arg1 glycosyltransferases 540:559 Several differentially expressed glycosyltransferases 507:559 Several differentially expressed glycosyltransferases found by RNA-seq 507:576 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 5 2 from analysis 838:845 arg1 MTC 854:856 the MTC 850:856 the MTC (n = 9 AD vs. 6 controls) 850:882 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 7 3 theme MGAT1 1048:1052 arg1 Upregulation 1032:1043 Upregulation 1032:1043 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation 1032:1130 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation, respectively, were reflected by increased concentrations of corresponding N-glycans. 37188790 5 4 theme spectrometry 805:816 arg1 analysis 838:845 mass spectrometry (MS)-based N-glycan analysis 800:845 mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls) 800:882 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 6 5 theme glycosylation-related 898:918 arg1 genes 920:924 glycosylation-related genes 898:924 glycosylation-related genes 898:924 About 80% of glycosylation-related genes were differentially expressed in at least one brain region of AD participants (adjusted p-values < 0.05). 37188790 10 6 theme N-glycosylation 1565:1579 arg1 expression 1551:1560 the expression 1547:1560 the expression of N-glycosylation and elongation genes 1547:1600 The critical transcription factors regulating the expression of N-glycosylation and elongation genes were predicted and found to include STAT1 and HSF5. 37188790 12 7 theme glycosyltransferase 1908:1926 arg1 expression 1928:1937 glycosyltransferase expression 1908:1937 glycosyltransferase expression that deserve further validation 1908:1969 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 8 8 theme polypeptide 1278:1288 arg1 N-acetylgalactosaminyltransferase 1290:1322 polypeptide N-acetylgalactosaminyltransferase 1278:1322 the polypeptide N-acetylgalactosaminyltransferase (GALNT) family 1274:1337 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 8 8 theme polypeptide 1278:1288 arg1 GALNT 1325:1329 GALNT 1325:1329 GALNT 1325:1329 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 5 9 from changes 744:750 arg1 glycosyltransferases 761:780 these glycosyltransferases 755:780 these glycosyltransferases 755:780 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 10 10 dep N-glycosylation 1565:1579 arg1 genes 1596:1600 genes 1596:1600 genes 1596:1600 The critical transcription factors regulating the expression of N-glycosylation and elongation genes were predicted and found to include STAT1 and HSF5. 37188790 4 11 theme medial 629:634 arg1 cortex 645:650 medial temporal cortex 629:650 human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls) 623:692 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 4 11 theme medial 629:634 arg1 MTC 653:655 MTC 653:655 MTC 653:655 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 12 12 theme individuals 2049:2059 arg1 brains 2027:2032 the brains 2023:2032 the brains of AD dementia individuals 2023:2059 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 8 13 theme enzymes 1427:1433 arg1 family 1417:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family 1343:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes 1343:1433 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 8 13 theme enzymes 1427:1433 arg1 expression 1260:1269 expression 1260:1269 expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family 1260:1337 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 12 14 theme dementia 2040:2047 arg1 individuals 2049:2059 AD dementia individuals 2037:2059 AD dementia individuals 2037:2059 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 4 15 theme human 623:627 arg1 samples 658:664 human medial temporal cortex (MTC) samples 623:664 human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls) 623:692 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 4 15 theme human 623:627 arg1 controls 684:691 n = 20 AD vs. 20 controls 667:691 n = 20 AD vs. 20 controls 667:691 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 3 16 theme RNA-seq 346:352 arg1 datasets 354:361 publicly available RNA-seq datasets 327:361 publicly available RNA-seq datasets covering seven brain regions 327:390 Using publicly available RNA-seq datasets covering seven brain regions and including 1724 samples, we identified glycosylation-related genes ubiquitously changed in individuals with AD. 37188790 8 17 theme alpha-N-acetylgalactosaminide 1347:1375 arg1 family 1417:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family 1343:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes 1343:1433 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 10 18 theme elongation 1585:1594 arg1 expression 1551:1560 the expression 1547:1560 the expression of N-glycosylation and elongation genes 1547:1600 The critical transcription factors regulating the expression of N-glycosylation and elongation genes were predicted and found to include STAT1 and HSF5. 37188790 12 19 theme expression 1928:1937 arg1 overview 1830:1837 an overview 1827:1837 an overview of glycosylation pathways affected by AD 1827:1878 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 12 19 theme expression 1928:1937 arg1 regulators 1894:1903 potential regulators 1884:1903 potential regulators of glycosyltransferase expression that deserve further validation 1884:1969 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 2 20 theme glycosylation-related 262:282 arg1 pathways 284:291 specific glycosylation-related pathways 253:291 specific glycosylation-related pathways 253:291 However, it is unknown which specific glycosylation-related pathways are altered in AD dementia. 37188790 7 21 link N-linked 1086:1093 arg1 formation 1102:1110 complex N-linked glycan formation 1078:1110 complex N-linked glycan formation 1078:1110 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation, respectively, were reflected by increased concentrations of corresponding N-glycans. 37188790 1 22 gly Glycosylation 121:133 arg1 brains 171:176 the brains 167:176 the brains of individuals with Alzheimer's disease (AD) 167:221 Glycosylation has been found to be altered in the brains of individuals with Alzheimer's disease (AD). 37188790 9 23 dep genes 1464:1468 arg1 PIGM 1477:1480 PIGM 1477:1480 PIGM 1477:1480 Several glycolipid-specific genes (UGT8, PIGM) were upregulated. 37188790 9 23 dep genes 1464:1468 arg1 UGT8 1471:1474 UGT8 1471:1474 UGT8 1471:1474 Several glycolipid-specific genes (UGT8, PIGM) were upregulated. 37188790 10 24 theme transcription 1514:1526 arg1 factors 1528:1534 The critical transcription factors 1501:1534 The critical transcription factors regulating the expression of N-glycosylation and elongation genes 1501:1600 The critical transcription factors regulating the expression of N-glycosylation and elongation genes were predicted and found to include STAT1 and HSF5. 37188790 2 25 theme specific 253:260 arg1 pathways 284:291 specific glycosylation-related pathways 253:291 specific glycosylation-related pathways 253:291 However, it is unknown which specific glycosylation-related pathways are altered in AD dementia. 37188790 1 26 theme individuals 181:191 arg1 brains 171:176 the brains 167:176 the brains of individuals with Alzheimer's disease (AD) 167:221 Glycosylation has been found to be altered in the brains of individuals with Alzheimer's disease (AD). 37188790 5 27 theme N-glycan 829:836 arg1 analysis 838:845 mass spectrometry (MS)-based N-glycan analysis 800:845 mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls) 800:882 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 4 28 theme Several 507:513 arg1 glycosyltransferases 540:559 Several differentially expressed glycosyltransferases 507:559 Several differentially expressed glycosyltransferases found by RNA-seq 507:576 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 7 29 theme N-linked 1086:1093 arg1 formation 1102:1110 complex N-linked glycan formation 1078:1110 complex N-linked glycan formation 1078:1110 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation, respectively, were reflected by increased concentrations of corresponding N-glycans. 37188790 10 30 theme critical 1505:1512 arg1 factors 1528:1534 The critical transcription factors 1501:1534 The critical transcription factors regulating the expression of N-glycosylation and elongation genes 1501:1600 The critical transcription factors regulating the expression of N-glycosylation and elongation genes were predicted and found to include STAT1 and HSF5. 37188790 2 31 theme dementia 311:318 arg1 AD 308:309 AD dementia 308:318 AD dementia 308:318 However, it is unknown which specific glycosylation-related pathways are altered in AD dementia. 37188790 11 32 dep N-glycosylation 1703:1717 arg1 glycosyltransferases 1734:1753 glycosyltransferases 1734:1753 glycosyltransferases 1734:1753 The miRNA predicted to be involved in regulating N-glycosylation and elongation glycosyltransferases were has-miR-1-3p and has-miR-16-5p, respectively. 37188790 5 33 theme expression 733:742 arg1 changes 744:750 expression changes 733:750 expression changes in these glycosyltransferases 733:780 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 0 34 theme Transcriptomic 0:13 arg1 analyses 28:35 Transcriptomic and glycomic analyses 0:35 Transcriptomic and glycomic analyses 0:35 Transcriptomic and glycomic analyses highlight pathway-specific glycosylation alterations unique to Alzheimer's disease. 37188790 7 35 theme glycan 1095:1100 arg1 formation 1102:1110 complex N-linked glycan formation 1078:1110 complex N-linked glycan formation 1078:1110 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation, respectively, were reflected by increased concentrations of corresponding N-glycans. 37188790 3 36 theme glycosylation-related 434:454 arg1 genes 456:460 glycosylation-related genes 434:460 glycosylation-related genes ubiquitously changed in individuals with AD 434:504 Using publicly available RNA-seq datasets covering seven brain regions and including 1724 samples, we identified glycosylation-related genes ubiquitously changed in individuals with AD. 37188790 3 37 theme brain 378:382 arg1 regions 384:390 seven brain regions 372:390 seven brain regions 372:390 Using publicly available RNA-seq datasets covering seven brain regions and including 1724 samples, we identified glycosylation-related genes ubiquitously changed in individuals with AD. 37188790 6 38 theme brain 972:976 arg1 p-values < 0.05 1014:1028 adjusted p-values < 0.05 1005:1028 adjusted p-values < 0.05 1005:1028 About 80% of glycosylation-related genes were differentially expressed in at least one brain region of AD participants (adjusted p-values < 0.05). 37188790 6 38 theme brain 972:976 arg1 region 978:983 at least one brain region 959:983 at least one brain region of AD participants (adjusted p-values < 0.05) 959:1029 About 80% of glycosylation-related genes were differentially expressed in at least one brain region of AD participants (adjusted p-values < 0.05). 37188790 12 39 theme AD 2037:2038 arg1 individuals 2049:2059 AD dementia individuals 2037:2059 AD dementia individuals 2037:2059 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 12 40 theme potential 1884:1892 arg1 regulators 1894:1903 potential regulators 1884:1903 potential regulators of glycosyltransferase expression that deserve further validation 1884:1969 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 4 41 theme samples 658:664 arg1 set 616:618 a different set 604:618 a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls) 604:692 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 4 41 theme samples 658:664 arg1 samples 658:664 human medial temporal cortex (MTC) samples 623:664 human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls) 623:692 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 4 41 theme samples 658:664 arg1 controls 684:691 n = 20 AD vs. 20 controls 667:691 n = 20 AD vs. 20 controls 667:691 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 0 42 theme glycomic 19:26 arg1 analyses 28:35 Transcriptomic and glycomic analyses 0:35 Transcriptomic and glycomic analyses 0:35 Transcriptomic and glycomic analyses highlight pathway-specific glycosylation alterations unique to Alzheimer's disease. 37188790 4 43 theme different 606:614 arg1 set 616:618 a different set 604:618 a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls) 604:692 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 4 43 theme different 606:614 arg1 samples 658:664 human medial temporal cortex (MTC) samples 623:664 human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls) 623:692 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 4 43 theme different 606:614 arg1 controls 684:691 n = 20 AD vs. 20 controls 667:691 n = 20 AD vs. 20 controls 667:691 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 7 44 theme complex 1078:1084 arg1 formation 1102:1110 complex N-linked glycan formation 1078:1110 complex N-linked glycan formation 1078:1110 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation, respectively, were reflected by increased concentrations of corresponding N-glycans. 37188790 6 45 theme genes 920:924 arg1 % 893:893 About 80% 885:893 About 80% of glycosylation-related genes 885:924 About 80% of glycosylation-related genes were differentially expressed in at least one brain region of AD participants (adjusted p-values < 0.05). 37188790 6 45 theme genes 920:924 arg1 genes 920:924 glycosylation-related genes 898:924 glycosylation-related genes 898:924 About 80% of glycosylation-related genes were differentially expressed in at least one brain region of AD participants (adjusted p-values < 0.05). 37188790 0 46 theme pathway-specific 47:62 arg1 alterations 78:88 pathway-specific glycosylation alterations 47:88 pathway-specific glycosylation alterations unique to Alzheimer's disease 47:118 Transcriptomic and glycomic analyses highlight pathway-specific glycosylation alterations unique to Alzheimer's disease. 37188790 9 47 theme glycolipid-specific 1444:1462 arg1 genes 1464:1468 Several glycolipid-specific genes 1436:1468 Several glycolipid-specific genes (UGT8, PIGM) 1436:1481 Several glycolipid-specific genes (UGT8, PIGM) were upregulated. 37188790 3 48 with individuals 486:496 arg1 AD 503:504 AD 503:504 AD 503:504 Using publicly available RNA-seq datasets covering seven brain regions and including 1724 samples, we identified glycosylation-related genes ubiquitously changed in individuals with AD. 37188790 7 49 theme N-glycans 1207:1215 arg1 concentrations 1175:1188 increased concentrations 1165:1188 increased concentrations of corresponding N-glycans 1165:1215 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation, respectively, were reflected by increased concentrations of corresponding N-glycans. 37188790 8 50 theme N-acetylgalactosaminyltransferase 1290:1322 arg1 family 1332:1337 the polypeptide N-acetylgalactosaminyltransferase (GALNT) family 1274:1337 the polypeptide N-acetylgalactosaminyltransferase (GALNT) family 1274:1337 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 5 51 theme n = 9 859:863 arg1 AD 865:866 n = 9 AD 859:866 n = 9 AD 859:866 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 7 52 theme increased 1165:1173 arg1 concentrations 1175:1188 increased concentrations 1165:1188 increased concentrations of corresponding N-glycans 1165:1215 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation, respectively, were reflected by increased concentrations of corresponding N-glycans. 37188790 6 53 theme participants 991:1002 arg1 p-values < 0.05 1014:1028 adjusted p-values < 0.05 1005:1028 adjusted p-values < 0.05 1005:1028 About 80% of glycosylation-related genes were differentially expressed in at least one brain region of AD participants (adjusted p-values < 0.05). 37188790 6 53 theme participants 991:1002 arg1 region 978:983 at least one brain region 959:983 at least one brain region of AD participants (adjusted p-values < 0.05) 959:1029 About 80% of glycosylation-related genes were differentially expressed in at least one brain region of AD participants (adjusted p-values < 0.05). 37188790 8 54 theme family 1332:1337 arg1 family 1417:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family 1343:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes 1343:1433 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 8 54 theme family 1332:1337 arg1 expression 1260:1269 expression 1260:1269 expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family 1260:1337 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 5 55 theme -based 822:827 arg1 analysis 838:845 mass spectrometry (MS)-based N-glycan analysis 800:845 mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls) 800:882 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 0 56 theme unique 90:95 arg1 alterations 78:88 pathway-specific glycosylation alterations 47:88 pathway-specific glycosylation alterations unique to Alzheimer's disease 47:118 Transcriptomic and glycomic analyses highlight pathway-specific glycosylation alterations unique to Alzheimer's disease. 37188790 8 57 theme ST6GALNAC 1406:1414 arg1 family 1417:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family 1343:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes 1343:1433 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 0 58 theme glycosylation 64:76 arg1 alterations 78:88 pathway-specific glycosylation alterations 47:88 pathway-specific glycosylation alterations unique to Alzheimer's disease 47:118 Transcriptomic and glycomic analyses highlight pathway-specific glycosylation alterations unique to Alzheimer's disease. 37188790 6 59 theme AD 988:989 arg1 participants 991:1002 AD participants 988:1002 AD participants 988:1002 About 80% of glycosylation-related genes were differentially expressed in at least one brain region of AD participants (adjusted p-values < 0.05). 37188790 12 60 theme pathways 1856:1863 arg1 overview 1830:1837 an overview 1827:1837 an overview of glycosylation pathways affected by AD 1827:1878 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 12 60 theme pathways 1856:1863 arg1 regulators 1894:1903 potential regulators 1884:1903 potential regulators of glycosyltransferase expression that deserve further validation 1884:1969 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 8 61 theme Isozyme-specific 1218:1233 arg1 changes 1235:1241 Isozyme-specific changes 1218:1241 Isozyme-specific changes 1218:1241 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 5 62 theme N-glycan-related 695:710 arg1 changes 712:718 N-glycan-related changes 695:718 N-glycan-related changes predicted by expression changes in these glycosyltransferases 695:780 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 8 63 located observed 1248:1255 arg1 family 1417:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family 1343:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes 1343:1433 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 8 63 located observed 1248:1255 arg1 expression 1260:1269 expression 1260:1269 expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family 1260:1337 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 8 63 located observed 1248:1255 arg2 changes 1235:1241 Isozyme-specific changes 1218:1241 Isozyme-specific changes 1218:1241 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 9 64 theme Several 1436:1442 arg1 genes 1464:1468 Several glycolipid-specific genes 1436:1468 Several glycolipid-specific genes (UGT8, PIGM) 1436:1481 Several glycolipid-specific genes (UGT8, PIGM) were upregulated. 37188790 12 65 theme glycosylation 1842:1854 arg1 pathways 1856:1863 glycosylation pathways 1842:1863 glycosylation pathways affected by AD 1842:1878 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 4 66 theme cortex 645:650 arg1 samples 658:664 human medial temporal cortex (MTC) samples 623:664 human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls) 623:692 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 4 66 theme cortex 645:650 arg1 controls 684:691 n = 20 AD vs. 20 controls 667:691 n = 20 AD vs. 20 controls 667:691 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 12 67 theme glycosylation 1988:2000 arg1 changes 2002:2008 glycosylation changes 1988:2008 glycosylation changes occurring in the brains of AD dementia individuals 1988:2059 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 12 68 theme further 1952:1958 arg1 validation 1960:1969 further validation 1952:1969 further validation 1952:1969 Our findings provide an overview of glycosylation pathways affected by AD and potential regulators of glycosyltransferase expression that deserve further validation and suggest that glycosylation changes occurring in the brains of AD dementia individuals are highly pathway-specific and unique to AD. 37188790 8 69 theme alpha-2,6-sialyltransferase 1377:1403 arg1 family 1417:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family 1343:1422 the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes 1343:1433 Isozyme-specific changes were observed in expression of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family and the alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) family of enzymes. 37188790 4 70 theme temporal 636:643 arg1 cortex 645:650 medial temporal cortex 629:650 human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls) 623:692 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 4 70 theme temporal 636:643 arg1 MTC 653:655 MTC 653:655 MTC 653:655 Several differentially expressed glycosyltransferases found by RNA-seq were confirmed by qPCR in a different set of human medial temporal cortex (MTC) samples (n = 20 AD vs. 20 controls). 37188790 5 71 dep MTC 854:856 arg1 AD 865:866 n = 9 AD 859:866 n = 9 AD 859:866 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 5 71 dep MTC 854:856 arg1 controls 874:881 6 controls 872:881 6 controls 872:881 N-glycan-related changes predicted by expression changes in these glycosyltransferases were confirmed by mass spectrometry (MS)-based N-glycan analysis in the MTC (n = 9 AD vs. 6 controls). 37188790 3 72 theme available 336:344 arg1 datasets 354:361 publicly available RNA-seq datasets 327:361 publicly available RNA-seq datasets covering seven brain regions 327:390 Using publicly available RNA-seq datasets covering seven brain regions and including 1724 samples, we identified glycosylation-related genes ubiquitously changed in individuals with AD. 37188790 7 73 theme B4GALT1 1058:1064 arg1 Upregulation 1032:1043 Upregulation 1032:1043 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation 1032:1130 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation, respectively, were reflected by increased concentrations of corresponding N-glycans. 37188790 7 74 theme corresponding 1193:1205 arg1 N-glycans 1207:1215 corresponding N-glycans 1193:1215 corresponding N-glycans 1193:1215 Upregulation of MGAT1 and B4GALT1 involved in complex N-linked glycan formation and galactosylation, respectively, were reflected by increased concentrations of corresponding N-glycans. 37188790 6 75 theme adjusted 1005:1012 arg1 p-values < 0.05 1014:1028 adjusted p-values < 0.05 1005:1028 adjusted p-values < 0.05 1005:1028 About 80% of glycosylation-related genes were differentially expressed in at least one brain region of AD participants (adjusted p-values < 0.05). 37188790 6 75 theme adjusted 1005:1012 arg1 region 978:983 at least one brain region 959:983 at least one brain region of AD participants (adjusted p-values < 0.05) 959:1029 About 80% of glycosylation-related genes were differentially expressed in at least one brain region of AD participants (adjusted p-values < 0.05). 35750689 0 0 theme dystroglycan 80:91 arg1 binding 93:99 dystroglycan binding 80:99 dystroglycan binding 80:99 Cell surface glycan engineering reveals that matriglycan alone can recapitulate dystroglycan binding and function. 35750689 5 1 dep dependent 897:905 arg1 dose 881:884 dose 881:884 dose 881:884 Finally, free matriglycan in a dose and length dependent manner inhibits viral infection of wildtype cells. 35750689 1 2 theme O-mannose 161:169 arg1 sites 171:175 O-mannose sites 161:175 O-mannose sites 161:175 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 5 3 from matriglycan 864:874 arg1 manner 907:912 a dose and length dependent manner 879:912 a dose and length dependent manner 879:912 Finally, free matriglycan in a dose and length dependent manner inhibits viral infection of wildtype cells. 35750689 6 4 theme ligand-binding 1210:1223 arg1 capacity 1225:1232 ligand-binding capacity 1210:1232 ligand-binding capacity 1210:1232 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 6 5 theme GP1 1068:1070 arg1 binding 1072:1078 Laminin and LASV GP1 binding 1051:1078 Laminin and LASV GP1 binding 1051:1078 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 6 6 theme Laminin 1051:1057 arg1 binding 1072:1078 Laminin and LASV GP1 binding 1051:1078 Laminin and LASV GP1 binding 1051:1078 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 6 7 theme LASV 1063:1066 arg1 binding 1072:1078 Laminin and LASV GP1 binding 1051:1078 Laminin and LASV GP1 binding 1051:1078 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 4 8 with O-mannosylation 750:764 arg1 matriglycans 771:782 matriglycans 771:782 matriglycans of sufficient length 771:803 Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length recovers infection with a Lassa-pseudovirus. 35750689 3 9 theme enzymatic 563:571 arg1 approach 585:592 an enzymatic engineering approach 560:592 an enzymatic engineering approach 560:592 Utilizing an enzymatic engineering approach, an N-linked glycoprotein was converted into a IIH6-positive Laminin-binding glycoprotein. 35750689 5 10 theme cells 951:955 arg1 infection 929:937 viral infection 923:937 viral infection of wildtype cells 923:955 Finally, free matriglycan in a dose and length dependent manner inhibits viral infection of wildtype cells. 35750689 4 11 theme deficient 721:729 arg1 cells 715:719 cells 715:719 cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length 715:803 Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length recovers infection with a Lassa-pseudovirus. 35750689 3 12 theme engineering 573:583 arg1 approach 585:592 an enzymatic engineering approach 560:592 an enzymatic engineering approach 560:592 Utilizing an enzymatic engineering approach, an N-linked glycoprotein was converted into a IIH6-positive Laminin-binding glycoprotein. 35750689 6 13 theme tunable 1150:1156 arg1 it 1142:1143 it 1142:1143 it 1142:1143 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 6 13 theme tunable 1150:1156 arg1 receptor 1158:1165 a tunable receptor 1148:1165 a tunable receptor for which increasing chain length enhances ligand-binding capacity 1148:1232 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 4 14 theme cells 715:719 arg1 surface 704:710 the surface 700:710 the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length 700:803 Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length recovers infection with a Lassa-pseudovirus. 35750689 0 15 theme surface 5:11 arg1 engineering 20:30 Cell surface glycan engineering 0:30 Cell surface glycan engineering 0:30 Cell surface glycan engineering reveals that matriglycan alone can recapitulate dystroglycan binding and function. 35750689 4 16 with α-DG 742:745 arg1 matriglycans 771:782 matriglycans 771:782 matriglycans of sufficient length 771:803 Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length recovers infection with a Lassa-pseudovirus. 35750689 3 17 gly glycoprotein 671:682 arg1 glycoprotein 671:682 a IIH6-positive Laminin-binding glycoprotein 639:682 a IIH6-positive Laminin-binding glycoprotein 639:682 Utilizing an enzymatic engineering approach, an N-linked glycoprotein was converted into a IIH6-positive Laminin-binding glycoprotein. 35750689 0 18 theme Cell 0:3 arg1 engineering 20:30 Cell surface glycan engineering 0:30 Cell surface glycan engineering 0:30 Cell surface glycan engineering reveals that matriglycan alone can recapitulate dystroglycan binding and function. 35750689 1 19 theme repeating 182:190 arg1 -Xylα1,3-GlcAβ1,3- 206:223 -Xylα1,3-GlcAβ1,3- 206:223 -Xylα1,3-GlcAβ1,3- 206:223 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 1 19 theme repeating 182:190 arg1 disaccharide 192:203 a repeating disaccharide 180:203 a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n 180:225 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 1 19 theme repeating 182:190 arg1 receptor 258:265 a receptor 256:265 a receptor for laminin-G domain-containing proteins 256:306 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 5 20 theme length 890:895 arg1 manner 907:912 a dose and length dependent manner 879:912 a dose and length dependent manner 879:912 Finally, free matriglycan in a dose and length dependent manner inhibits viral infection of wildtype cells. 35750689 1 21 theme laminin-G 271:279 arg1 proteins 299:306 laminin-G domain-containing proteins 271:306 laminin-G domain-containing proteins 271:306 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 2 22 theme length-dependent 452:467 arg1 binding 469:475 length-dependent binding 452:475 length-dependent binding to Laminin, Lassa virus GP1, and the clinically-important antibody IIH6 452:547 Using chemoenzymatically synthesized matriglycans printed as a microarray, we demonstrate length-dependent binding to Laminin, Lassa virus GP1, and the clinically-important antibody IIH6. 35750689 0 23 theme glycan 13:18 arg1 engineering 20:30 Cell surface glycan engineering 0:30 Cell surface glycan engineering 0:30 Cell surface glycan engineering reveals that matriglycan alone can recapitulate dystroglycan binding and function. 35750689 1 24 theme domain-containing 281:297 arg1 proteins 299:306 laminin-G domain-containing proteins 271:306 laminin-G domain-containing proteins 271:306 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 3 25 theme N-linked 598:605 arg1 glycoprotein 607:618 an N-linked glycoprotein 595:618 an N-linked glycoprotein 595:618 Utilizing an enzymatic engineering approach, an N-linked glycoprotein was converted into a IIH6-positive Laminin-binding glycoprotein. 35750689 5 26 theme free 859:862 arg1 matriglycan 864:874 free matriglycan 859:874 free matriglycan in a dose and length dependent manner 859:912 Finally, free matriglycan in a dose and length dependent manner inhibits viral infection of wildtype cells. 35750689 5 27 theme viral 923:927 arg1 infection 929:937 viral infection 923:937 viral infection of wildtype cells 923:955 Finally, free matriglycan in a dose and length dependent manner inhibits viral infection of wildtype cells. 35750689 1 28 mod modified 149:156 arg3 receptor 258:265 a receptor 256:265 a receptor for laminin-G domain-containing proteins 256:306 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 1 28 mod modified 149:156 arg3 disaccharide 192:203 a repeating disaccharide 180:203 a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n 180:225 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 1 28 mod modified 149:156 arg1 α-DG 131:134 α-DG 131:134 α-DG 131:134 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 1 28 mod modified 149:156 arg3 -Xylα1,3-GlcAβ1,3- 206:223 -Xylα1,3-GlcAβ1,3- 206:223 -Xylα1,3-GlcAβ1,3- 206:223 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 1 28 mod modified 149:156 arg1 α-Dystroglycan 115:128 α-Dystroglycan 115:128 α-Dystroglycan (α-DG) 115:135 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 6 29 theme IIH6 1036:1039 arg1 staining 1041:1048 IIH6 staining 1036:1048 IIH6 staining 1036:1048 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 3 30 theme IIH6-positive 641:653 arg1 glycoprotein 671:682 a IIH6-positive Laminin-binding glycoprotein 639:682 a IIH6-positive Laminin-binding glycoprotein 639:682 Utilizing an enzymatic engineering approach, an N-linked glycoprotein was converted into a IIH6-positive Laminin-binding glycoprotein. 35750689 4 31 theme surface 704:710 arg1 Engineering 685:695 Engineering 685:695 Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length 685:803 Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length recovers infection with a Lassa-pseudovirus. 35750689 2 32 theme virus 495:499 arg1 GP1 501:503 Lassa virus GP1 489:503 Lassa virus GP1 489:503 Using chemoenzymatically synthesized matriglycans printed as a microarray, we demonstrate length-dependent binding to Laminin, Lassa virus GP1, and the clinically-important antibody IIH6. 35750689 3 33 link N-linked 598:605 arg1 glycoprotein 607:618 an N-linked glycoprotein 595:618 an N-linked glycoprotein 595:618 Utilizing an enzymatic engineering approach, an N-linked glycoprotein was converted into a IIH6-positive Laminin-binding glycoprotein. 35750689 2 34 theme Lassa 489:493 arg1 GP1 501:503 Lassa virus GP1 489:503 Lassa virus GP1 489:503 Using chemoenzymatically synthesized matriglycans printed as a microarray, we demonstrate length-dependent binding to Laminin, Lassa virus GP1, and the clinically-important antibody IIH6. 35750689 4 35 with infection 814:822 arg1 Lassa-pseudovirus 831:847 a Lassa-pseudovirus 829:847 a Lassa-pseudovirus 829:847 Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length recovers infection with a Lassa-pseudovirus. 35750689 3 36 gly glycoprotein 607:618 arg1 glycoprotein 607:618 an N-linked glycoprotein 595:618 an N-linked glycoprotein 595:618 Utilizing an enzymatic engineering approach, an N-linked glycoprotein was converted into a IIH6-positive Laminin-binding glycoprotein. 35750689 1 37 theme old-world 324:332 arg1 arenaviruses 334:345 old-world arenaviruses 324:345 old-world arenaviruses 324:345 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 4 38 theme length 798:803 arg1 matriglycans 771:782 matriglycans 771:782 matriglycans of sufficient length 771:803 Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length recovers infection with a Lassa-pseudovirus. 35750689 3 39 theme Laminin-binding 655:669 arg1 glycoprotein 671:682 a IIH6-positive Laminin-binding glycoprotein 639:682 a IIH6-positive Laminin-binding glycoprotein 639:682 Utilizing an enzymatic engineering approach, an N-linked glycoprotein was converted into a IIH6-positive Laminin-binding glycoprotein. 35750689 6 40 theme increasing 1177:1186 arg1 length 1194:1199 increasing chain length 1177:1199 increasing chain length 1177:1199 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 6 41 from receptor 1158:1165 arg1 model 1127:1131 a model 1125:1131 a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity 1125:1232 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 4 42 theme sufficient 787:796 arg1 length 798:803 sufficient length 787:803 sufficient length 787:803 Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length recovers infection with a Lassa-pseudovirus. 35750689 6 43 theme chain 1188:1192 arg1 length 1194:1199 increasing chain length 1177:1199 increasing chain length 1177:1199 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 2 44 theme antibody 535:542 arg1 IIH6 544:547 the clinically-important antibody IIH6 510:547 the clinically-important antibody IIH6 510:547 Using chemoenzymatically synthesized matriglycans printed as a microarray, we demonstrate length-dependent binding to Laminin, Lassa virus GP1, and the clinically-important antibody IIH6. 35750689 1 45 dep disaccharide 192:203 arg1 n 225:225 n 225:225 a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n 180:225 α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. 35750689 5 46 theme wildtype 942:949 arg1 cells 951:955 wildtype cells 942:955 wildtype cells 942:955 Finally, free matriglycan in a dose and length dependent manner inhibits viral infection of wildtype cells. 35750689 6 47 theme Lassa-pseudovirus 1085:1101 arg1 infection 1103:1111 Lassa-pseudovirus infection 1085:1111 Lassa-pseudovirus infection 1085:1111 These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity. 35750689 2 48 theme clinically-important 514:533 arg1 IIH6 544:547 the clinically-important antibody IIH6 510:547 the clinically-important antibody IIH6 510:547 Using chemoenzymatically synthesized matriglycans printed as a microarray, we demonstrate length-dependent binding to Laminin, Lassa virus GP1, and the clinically-important antibody IIH6. 35750689 5 49 theme dependent 897:905 arg1 manner 907:912 a dose and length dependent manner 879:912 a dose and length dependent manner 879:912 Finally, free matriglycan in a dose and length dependent manner inhibits viral infection of wildtype cells. 35750689 2 50 theme synthesized 387:397 arg1 matriglycans 399:410 chemoenzymatically synthesized matriglycans 368:410 chemoenzymatically synthesized matriglycans printed as a microarray 368:434 Using chemoenzymatically synthesized matriglycans printed as a microarray, we demonstrate length-dependent binding to Laminin, Lassa virus GP1, and the clinically-important antibody IIH6. 34672530 4 0 with immunization 730:741 arg1 three 756:760 three 756:760 three 756:760 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 0 with immunization 730:741 arg1 CPMV-1209 816:824 CPMV-1209 816:824 CPMV-1209 816:824 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 0 with immunization 730:741 arg1 CPMV-988 791:798 CPMV-988 791:798 CPMV-988 791:798 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 0 with immunization 730:741 arg1 vaccines 781:788 these candidate vaccines 765:788 these candidate vaccines 765:788 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 0 with immunization 730:741 arg1 CPMV-1173 801:809 CPMV-1173 801:809 CPMV-1173 801:809 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 5 1 theme lower 1241:1245 arg1 magnitude 1247:1255 a lower magnitude 1239:1255 a lower magnitude compared to the soluble formulations 1239:1292 A pentavalent slow-release implant comprising all five peptides displayed on the CPMV elicited anti-S protein and epitope-specific antibody titers, albeit at a lower magnitude compared to the soluble formulations. 34672530 7 2 theme RNA 1434:1436 arg1 Loss 1426:1429 Loss 1426:1429 Loss of RNA 1426:1436 Loss of RNA may be a reason for the lower efficacy of the implants. 34672530 7 2 theme RNA 1434:1436 arg1 reason 1447:1452 a reason 1445:1452 a reason for the lower efficacy of the implants 1445:1491 Loss of RNA may be a reason for the lower efficacy of the implants. 34672530 4 3 dep second 1057:1062 arg1 boost 1064:1068 boost 1064:1068 boost 1064:1068 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 8 4 theme conformational 1771:1784 arg1 changes 1786:1792 conformational changes 1771:1792 conformational changes 1771:1792 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 0 5 theme Acute 106:110 arg1 Coronavirus 133:143 the Severe Acute Respiratory Syndrome Coronavirus 95:143 the Severe Acute Respiratory Syndrome Coronavirus 95:143 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus. 34672530 4 6 theme acute 885:889 arg1 coronavirus 912:922 the severe acute respiratory syndrome coronavirus 874:922 the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro 874:942 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 6 theme acute 885:889 arg1 SARS-CoV 925:932 SARS-CoV 925:932 SARS-CoV 925:932 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 3 7 theme severe 572:577 arg1 syndrome 597:604 severe acute respiratory syndrome 572:604 recovered severe acute respiratory syndrome (SARS) patients 562:620 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 3 7 theme severe 572:577 arg1 SARS 607:610 SARS 607:610 SARS 607:610 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 5 8 theme epitope-specific 1195:1210 arg1 titers 1221:1226 epitope-specific antibody titers 1195:1226 epitope-specific antibody titers 1195:1226 A pentavalent slow-release implant comprising all five peptides displayed on the CPMV elicited anti-S protein and epitope-specific antibody titers, albeit at a lower magnitude compared to the soluble formulations. 34672530 0 9 theme Severe 99:104 arg1 Coronavirus 133:143 the Severe Acute Respiratory Syndrome Coronavirus 95:143 the Severe Acute Respiratory Syndrome Coronavirus 95:143 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus. 34672530 4 10 theme severe 878:883 arg1 coronavirus 912:922 the severe acute respiratory syndrome coronavirus 874:922 the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro 874:942 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 10 theme severe 878:883 arg1 SARS-CoV 925:932 SARS-CoV 925:932 SARS-CoV 925:932 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 2 11 from epitopes 357:364 arg1 protein 375:381 the S protein 369:381 the S protein 369:381 Targeting conserved epitopes on the S protein offers the potential for pan-beta-coronavirus vaccines that could prevent future pandemics. 34672530 3 12 theme acute 579:583 arg1 syndrome 597:604 severe acute respiratory syndrome 572:604 recovered severe acute respiratory syndrome (SARS) patients 562:620 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 3 12 theme acute 579:583 arg1 SARS 607:610 SARS 607:610 SARS 607:610 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 5 13 theme antibody 1212:1219 arg1 titers 1221:1226 epitope-specific antibody titers 1195:1226 epitope-specific antibody titers 1195:1226 A pentavalent slow-release implant comprising all five peptides displayed on the CPMV elicited anti-S protein and epitope-specific antibody titers, albeit at a lower magnitude compared to the soluble formulations. 34672530 0 14 theme Syndrome 124:131 arg1 Coronavirus 133:143 the Severe Acute Respiratory Syndrome Coronavirus 95:143 the Severe Acute Respiratory Syndrome Coronavirus 95:143 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus. 34672530 4 15 theme antibody 841:848 arg1 titers 850:855 high antibody titers 836:855 high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks) 836:1078 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 8 16 theme natural 1737:1743 arg1 epitope 1745:1751 the natural epitope 1733:1751 the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans 1733:1828 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 8 17 from differences 1718:1728 arg1 epitope 1745:1751 the natural epitope 1733:1751 the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans 1733:1828 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 10 18 theme versatile 1970:1978 arg1 platform 1992:1999 a versatile vaccination platform 1968:1999 a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases 1968:2102 The technology discussed here is a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases. 34672530 10 18 theme versatile 1970:1978 arg1 technology 1939:1948 The technology 1935:1948 The technology discussed here 1935:1963 The technology discussed here is a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases. 34672530 0 19 theme Respiratory 112:122 arg1 Coronavirus 133:143 the Severe Acute Respiratory Syndrome Coronavirus 95:143 the Severe Acute Respiratory Syndrome Coronavirus 95:143 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus. 34672530 4 20 theme high 836:839 arg1 titers 850:855 high antibody titers 836:855 high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks) 836:1078 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 3 21 from epitopes 500:507 arg1 surface 630:636 the surface 626:636 the surface of the cowpea mosaic virus (CPMV) 626:670 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 3 22 theme recovered 562:570 arg1 patients 613:620 recovered severe acute respiratory syndrome (SARS) patients 562:620 recovered severe acute respiratory syndrome (SARS) patients 562:620 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 10 23 theme other 2028:2032 arg1 diseases 2034:2041 other diseases 2028:2041 other diseases 2028:2041 The technology discussed here is a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases. 34672530 4 24 theme early 958:962 arg1 profile 975:981 an early Th1-biased profile 955:981 an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks) 955:1078 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 24 theme early 958:962 arg1 weeks 988:992 2-4 weeks 984:992 2-4 weeks 984:992 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 0 25 theme Mosaic 7:12 arg1 Virus 14:18 Cowpea Mosaic Virus 0:18 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes 0:78 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus. 34672530 5 26 theme pentavalent 1083:1093 arg1 implant 1108:1114 A pentavalent slow-release implant 1081:1114 A pentavalent slow-release implant comprising all five peptides displayed on the CPMV 1081:1165 A pentavalent slow-release implant comprising all five peptides displayed on the CPMV elicited anti-S protein and epitope-specific antibody titers, albeit at a lower magnitude compared to the soluble formulations. 34672530 9 27 theme cross-protective 1839:1854 arg1 candidate 1864:1872 a cross-protective vaccine candidate 1837:1872 a cross-protective vaccine candidate 1837:1872 While a cross-protective vaccine candidate was not developed, a multivalent SARS vaccine was developed. 34672530 8 28 link N-linked 1813:1820 arg1 glycans 1822:1828 N-linked glycans 1813:1828 N-linked glycans 1813:1828 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 0 29 theme Cowpea 0:5 arg1 Virus 14:18 Cowpea Mosaic Virus 0:18 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes 0:78 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus. 34672530 4 30 theme mice 746:749 arg1 immunization 730:741 Prime-boost immunization 718:741 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, 718:825 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 8 31 dep epitopes 1522:1529 arg1 1173 1537:1540 1173 1537:1540 1173 1537:1540 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 8 31 dep epitopes 1522:1529 arg1 1209 1547:1550 1209 1547:1550 1209 1547:1550 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 0 32 theme Nanoparticle 20:31 arg1 Candidates 41:50 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates 0:50 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes 0:78 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus. 34672530 1 33 theme host-cell 275:283 arg1 receptors 285:293 host-cell receptors 275:293 host-cell receptors 275:293 The development of vaccines against coronaviruses has focused on the spike (S) protein, which is required for the recognition of host-cell receptors and thus elicits neutralizing antibodies. 34672530 8 34 theme glycans 1822:1828 arg1 changes 1786:1792 conformational changes 1771:1792 conformational changes 1771:1792 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 8 34 theme glycans 1822:1828 arg1 presence 1801:1808 the presence 1797:1808 the presence of N-linked glycans 1797:1828 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 3 35 theme respiratory 585:595 arg1 syndrome 597:604 severe acute respiratory syndrome 572:604 recovered severe acute respiratory syndrome (SARS) patients 562:620 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 3 35 theme respiratory 585:595 arg1 SARS 607:610 SARS 607:610 SARS 607:610 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 3 36 from patients 613:620 arg1 sera 552:555 the convalescent sera 535:555 the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients 535:620 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 1 37 theme spike 215:219 arg1 protein 225:231 the spike (S) protein 211:231 the spike (S) protein 211:231 The development of vaccines against coronaviruses has focused on the spike (S) protein, which is required for the recognition of host-cell receptors and thus elicits neutralizing antibodies. 34672530 0 38 theme Virus 14:18 arg1 Candidates 41:50 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates 0:50 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes 0:78 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus. 34672530 1 39 theme receptors 285:293 arg1 recognition 260:270 the recognition 256:270 the recognition of host-cell receptors 256:293 The development of vaccines against coronaviruses has focused on the spike (S) protein, which is required for the recognition of host-cell receptors and thus elicits neutralizing antibodies. 34672530 8 40 theme N-linked 1813:1820 arg1 glycans 1822:1828 N-linked glycans 1813:1828 N-linked glycans 1813:1828 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 3 41 theme virus 659:663 arg1 surface 630:636 the surface 626:636 the surface of the cowpea mosaic virus (CPMV) 626:670 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 3 42 theme syndrome 597:604 arg1 patients 613:620 recovered severe acute respiratory syndrome (SARS) patients 562:620 recovered severe acute respiratory syndrome (SARS) patients 562:620 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 9 43 theme vaccine 1856:1862 arg1 candidate 1864:1872 a cross-protective vaccine candidate 1837:1872 a cross-protective vaccine candidate 1837:1872 While a cross-protective vaccine candidate was not developed, a multivalent SARS vaccine was developed. 34672530 3 44 theme B-cell 493:498 arg1 epitopes 500:507 five B-cell epitopes 488:507 five B-cell epitopes 488:507 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 5 45 theme anti-S 1176:1181 arg1 protein 1183:1189 anti-S protein 1176:1189 anti-S protein 1176:1189 A pentavalent slow-release implant comprising all five peptides displayed on the CPMV elicited anti-S protein and epitope-specific antibody titers, albeit at a lower magnitude compared to the soluble formulations. 34672530 7 46 theme implants 1484:1491 arg1 efficacy 1468:1475 the lower efficacy 1458:1475 the lower efficacy of the implants 1458:1491 Loss of RNA may be a reason for the lower efficacy of the implants. 34672530 0 47 theme Vaccine 33:39 arg1 Candidates 41:50 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates 0:50 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes 0:78 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus. 34672530 6 48 theme RNA 1394:1396 arg1 loss 1386:1389 loss 1386:1389 loss 1386:1389 While the CPMV remained intact when released from the PLGA implants, processing results in loss of RNA, which acts as an adjuvant. 34672530 6 48 theme RNA 1394:1396 arg1 adjuvant 1416:1423 adjuvant 1416:1423 adjuvant 1416:1423 While the CPMV remained intact when released from the PLGA implants, processing results in loss of RNA, which acts as an adjuvant. 34672530 3 49 theme cowpea 645:650 arg1 virus 659:663 the cowpea mosaic virus 641:663 the cowpea mosaic virus (CPMV) 641:670 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 3 49 theme cowpea 645:650 arg1 CPMV 666:669 CPMV 666:669 CPMV 666:669 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 2 50 theme future 457:462 arg1 pandemics 464:472 future pandemics 457:472 future pandemics 457:472 Targeting conserved epitopes on the S protein offers the potential for pan-beta-coronavirus vaccines that could prevent future pandemics. 34672530 2 51 theme pan-beta-coronavirus 408:427 arg1 vaccines 429:436 pan-beta-coronavirus vaccines 408:436 pan-beta-coronavirus vaccines that could prevent future pandemics 408:472 Targeting conserved epitopes on the S protein offers the potential for pan-beta-coronavirus vaccines that could prevent future pandemics. 34672530 0 52 theme Peptide 63:69 arg1 Epitopes 71:78 Peptide Epitopes 63:78 Peptide Epitopes 63:78 Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus. 34672530 4 53 theme syndrome 903:910 arg1 coronavirus 912:922 the severe acute respiratory syndrome coronavirus 874:922 the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro 874:942 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 53 theme syndrome 903:910 arg1 SARS-CoV 925:932 SARS-CoV 925:932 SARS-CoV 925:932 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 3 54 theme mosaic 652:657 arg1 virus 659:663 the cowpea mosaic virus 641:663 the cowpea mosaic virus (CPMV) 641:670 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 3 54 theme mosaic 652:657 arg1 CPMV 666:669 CPMV 666:669 CPMV 666:669 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 10 55 theme infectious 2084:2093 arg1 diseases 2095:2102 infectious diseases 2084:2102 infectious diseases 2084:2102 The technology discussed here is a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases. 34672530 4 56 theme Prime-boost 718:728 arg1 immunization 730:741 Prime-boost immunization 718:741 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, 718:825 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 1 57 theme neutralizing 312:323 arg1 antibodies 325:334 neutralizing antibodies 312:334 neutralizing antibodies 312:334 The development of vaccines against coronaviruses has focused on the spike (S) protein, which is required for the recognition of host-cell receptors and thus elicits neutralizing antibodies. 34672530 4 58 theme respiratory 891:901 arg1 coronavirus 912:922 the severe acute respiratory syndrome coronavirus 874:922 the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro 874:942 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 58 theme respiratory 891:901 arg1 SARS-CoV 925:932 SARS-CoV 925:932 SARS-CoV 925:932 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 7 59 theme lower 1462:1466 arg1 efficacy 1468:1475 the lower efficacy 1458:1475 the lower efficacy of the implants 1458:1491 Loss of RNA may be a reason for the lower efficacy of the implants. 34672530 8 60 theme candidates 1660:1669 arg1 none 1640:1643 none 1640:1643 none of the vaccine candidates 1640:1669 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 2 61 theme conserved 347:355 arg1 epitopes 357:364 conserved epitopes 347:364 conserved epitopes on the S protein 347:381 Targeting conserved epitopes on the S protein offers the potential for pan-beta-coronavirus vaccines that could prevent future pandemics. 34672530 4 62 from coronavirus 912:922 arg1 vitro 938:942 vitro 938:942 vitro 938:942 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 8 63 theme vaccine 1652:1658 arg1 candidates 1660:1669 the vaccine candidates 1648:1669 the vaccine candidates 1648:1669 Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. 34672530 10 64 theme vaccination 1980:1990 arg1 platform 1992:1999 a versatile vaccination platform 1968:1999 a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases 1968:2102 The technology discussed here is a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases. 34672530 10 64 theme vaccination 1980:1990 arg1 technology 1939:1948 The technology 1935:1948 The technology discussed here 1935:1963 The technology discussed here is a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases. 34672530 4 65 theme vaccines 781:788 arg1 three 756:760 three 756:760 three 756:760 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 65 theme vaccines 781:788 arg1 CPMV-1209 816:824 CPMV-1209 816:824 CPMV-1209 816:824 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 65 theme vaccines 781:788 arg1 CPMV-988 791:798 CPMV-988 791:798 CPMV-988 791:798 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 65 theme vaccines 781:788 arg1 vaccines 781:788 these candidate vaccines 765:788 these candidate vaccines 765:788 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 65 theme vaccines 781:788 arg1 CPMV-1173 801:809 CPMV-1173 801:809 CPMV-1173 801:809 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 66 theme candidate 771:779 arg1 vaccines 781:788 these candidate vaccines 765:788 these candidate vaccines 765:788 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 1 67 theme vaccines 165:172 arg1 development 150:160 The development 146:160 The development of vaccines against coronaviruses 146:194 The development of vaccines against coronaviruses has focused on the spike (S) protein, which is required for the recognition of host-cell receptors and thus elicits neutralizing antibodies. 34672530 5 68 theme soluble 1273:1279 arg1 formulations 1281:1292 the soluble formulations 1269:1292 the soluble formulations 1269:1292 A pentavalent slow-release implant comprising all five peptides displayed on the CPMV elicited anti-S protein and epitope-specific antibody titers, albeit at a lower magnitude compared to the soluble formulations. 34672530 1 69 dep spike 215:219 arg1 S 222:222 S 222:222 S 222:222 The development of vaccines against coronaviruses has focused on the spike (S) protein, which is required for the recognition of host-cell receptors and thus elicits neutralizing antibodies. 34672530 9 70 theme multivalent 1895:1905 arg1 vaccine 1912:1918 a multivalent SARS vaccine 1893:1918 a multivalent SARS vaccine 1893:1918 While a cross-protective vaccine candidate was not developed, a multivalent SARS vaccine was developed. 34672530 3 71 theme convalescent 539:550 arg1 sera 552:555 the convalescent sera 535:555 the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients 535:620 We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. 34672530 4 72 theme Th1-biased 964:973 arg1 profile 975:981 an early Th1-biased profile 955:981 an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks) 955:1078 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 4 72 theme Th1-biased 964:973 arg1 weeks 988:992 2-4 weeks 984:992 2-4 weeks 984:992 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 5 73 theme slow-release 1095:1106 arg1 implant 1108:1114 A pentavalent slow-release implant 1081:1114 A pentavalent slow-release implant comprising all five peptides displayed on the CPMV 1081:1165 A pentavalent slow-release implant comprising all five peptides displayed on the CPMV elicited anti-S protein and epitope-specific antibody titers, albeit at a lower magnitude compared to the soluble formulations. 34672530 4 74 theme Th2-biased 1023:1032 arg1 profile 1034:1040 a slightly Th2-biased profile 1012:1040 a slightly Th2-biased profile just after the second boost (6 weeks) 1012:1078 Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). 34672530 9 75 theme SARS 1907:1910 arg1 vaccine 1912:1918 a multivalent SARS vaccine 1893:1918 a multivalent SARS vaccine 1893:1918 While a cross-protective vaccine candidate was not developed, a multivalent SARS vaccine was developed. 34672530 2 76 theme S 373:373 arg1 protein 375:381 the S protein 369:381 the S protein 369:381 Targeting conserved epitopes on the S protein offers the potential for pan-beta-coronavirus vaccines that could prevent future pandemics. 34672530 6 77 theme PLGA 1349:1352 arg1 implants 1354:1361 the PLGA implants 1345:1361 the PLGA implants 1345:1361 While the CPMV remained intact when released from the PLGA implants, processing results in loss of RNA, which acts as an adjuvant. 35012346 17 0 theme polarized 2209:2217 arg1 cells 2254:2258 human primary cervical epithelial cells 2220:2258 human primary cervical epithelial cells 2220:2258 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 17 0 theme polarized 2209:2217 arg1 adherence 2170:2178 HIV adherence 2166:2178 HIV adherence 2166:2178 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 11 1 theme Pex 1413:1415 arg1 monolayer 1422:1430 an intact Pex cell monolayer 1403:1430 an intact Pex cell monolayer 1403:1430 Using Pex cells in a Transwell model system, we show that, following transcytosis across an intact Pex cell monolayer, HIV-1 is able to infect TZM-bl reporter cells. 35012346 1 2 theme CD4-positive 249:260 arg1 cells 264:268 subepithelial CD4-positive T cells 235:268 subepithelial CD4-positive T cells 235:268 Transmission of HIV across the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells is not fully understood. 35012346 17 3 theme human 2220:2224 arg1 cells 2254:2258 human primary cervical epithelial cells 2220:2258 human primary cervical epithelial cells 2220:2258 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 17 3 theme human 2220:2224 arg1 adherence 2170:2178 HIV adherence 2166:2178 HIV adherence 2166:2178 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 13 4 theme efficient 1673:1681 arg1 pathway 1683:1689 an efficient pathway 1670:1689 an efficient pathway for HIV-1 transmission in women 1670:1721 These studies indicate that CR3/Pex may constitute an efficient pathway for HIV-1 transmission in women and also demonstrate strategies that may prevent transmission via this pathway. 35012346 10 5 gly glycoprotein 1139:1150 arg1 glycoprotein 1139:1150 the HIV-1 envelope glycoprotein 1120:1150 the HIV-1 envelope glycoprotein 1120:1150 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 6 6 theme alpha 736:740 arg1 subunit 742:748 the CR3 alpha subunit 728:748 the CR3 alpha subunit 728:748 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 8 7 theme HIV 937:939 arg1 N-glycans 941:949 HIV N-glycans 937:949 HIV N-glycans 937:949 Man5 pentasaccharide, representative of HIV N-glycans, could compete with HIV-1 for CR3 binding. 35012346 18 8 theme unique 2277:2282 arg1 role 2284:2287 a unique role 2275:2287 a unique role for CR3 on epithelial cells in dually facilitating HIV-1 attachment and entry 2275:2365 This suggests a unique role for CR3 on epithelial cells in dually facilitating HIV-1 attachment and entry. 35012346 10 9 theme Pex 1303:1305 arg1 cells 1307:1311 Pex cells 1303:1311 Pex cells 1303:1311 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 2 10 theme epithelial 304:313 arg1 cells 315:319 Cervical epithelial cells 295:319 Cervical epithelial cells 295:319 Cervical epithelial cells express complement receptor 3 (CR3) (integrin αMβ2 or CD11b/CD18). 35012346 1 11 theme mucosal 176:182 arg1 surface 184:190 the mucosal surface 172:190 the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells 172:268 Transmission of HIV across the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells is not fully understood. 35012346 13 12 from pathway 1683:1689 arg1 women 1717:1721 women 1717:1721 women 1717:1721 These studies indicate that CR3/Pex may constitute an efficient pathway for HIV-1 transmission in women and also demonstrate strategies that may prevent transmission via this pathway. 35012346 19 13 theme HIV-CR3 2372:2378 arg1 interaction 2380:2390 The HIV-CR3 interaction 2368:2390 The HIV-CR3 interaction 2368:2390 The HIV-CR3 interaction may constitute an efficient pathway for HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier. 35012346 1 14 theme female 199:204 arg1 tract 219:223 the female reproductive tract 195:223 the female reproductive tract 195:223 Transmission of HIV across the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells is not fully understood. 35012346 19 15 theme HIV 2432:2434 arg1 delivery 2436:2443 HIV delivery 2432:2443 HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier 2432:2546 The HIV-CR3 interaction may constitute an efficient pathway for HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier. 35012346 11 16 theme cell 1417:1420 arg1 monolayer 1422:1430 an intact Pex cell monolayer 1403:1430 an intact Pex cell monolayer 1403:1430 Using Pex cells in a Transwell model system, we show that, following transcytosis across an intact Pex cell monolayer, HIV-1 is able to infect TZM-bl reporter cells. 35012346 5 17 theme recombinant 646:656 arg1 CR3 658:660 recombinant CR3 646:660 recombinant CR3 646:660 Here, we show that HIV-1 strains bound with high affinity to recombinant CR3 in biophysical assays. 35012346 19 18 theme efficient 2410:2418 arg1 pathway 2420:2426 an efficient pathway 2407:2426 an efficient pathway for HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier 2407:2546 The HIV-CR3 interaction may constitute an efficient pathway for HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier. 35012346 10 19 theme HIV-1 1124:1128 arg1 glycoprotein 1139:1150 the HIV-1 envelope glycoprotein 1120:1150 the HIV-1 envelope glycoprotein 1120:1150 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 0 20 theme Intact 60:65 arg1 Barrier 92:98 an Intact Cervical Epithelial Cell Barrier 57:98 an Intact Cervical Epithelial Cell Barrier 57:98 Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women. 35012346 19 21 theme subepithelial 2448:2460 arg1 lymphocytes 2462:2472 subepithelial lymphocytes 2448:2472 subepithelial lymphocytes 2448:2472 The HIV-CR3 interaction may constitute an efficient pathway for HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier. 35012346 17 22 theme high 2094:2097 arg1 affinity 2099:2106 high affinity 2094:2106 high affinity 2094:2106 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 0 23 theme Epithelial 76:85 arg1 Barrier 92:98 an Intact Cervical Epithelial Cell Barrier 57:98 an Intact Cervical Epithelial Cell Barrier 57:98 Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women. 35012346 12 24 theme small-molecule 1572:1585 arg1 drugs 1587:1591 CR3-binding small-molecule drugs 1560:1591 CR3-binding small-molecule drugs 1560:1591 Targeting the HIV-CR3 interaction using antibodies, mannose-binding lectins, or CR3-binding small-molecule drugs blocked HIV transcytosis. 35012346 18 25 theme HIV-1 2340:2344 arg1 attachment 2346:2355 HIV-1 attachment 2340:2355 HIV-1 attachment 2340:2355 This suggests a unique role for CR3 on epithelial cells in dually facilitating HIV-1 attachment and entry. 35012346 19 26 theme epithelial 2529:2538 arg1 barrier 2540:2546 an intact cervical epithelial barrier 2510:2546 an intact cervical epithelial barrier 2510:2546 The HIV-CR3 interaction may constitute an efficient pathway for HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier. 35012346 17 27 dep adherence 2170:2178 arg1 to 2180:2181 to 2180:2181 to 2180:2181 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 16 28 theme Cervical 1987:1994 arg1 cells 2007:2011 Cervical epithelial cells 1987:2011 Cervical epithelial cells 1987:2011 Cervical epithelial cells have a protein called CR3 on their surface. 35012346 7 29 from glycans 824:830 arg1 surface 843:849 the HIV surface 835:849 the HIV surface 835:849 Mannosylated glycans on the HIV surface were a high-affinity ligand for the I-domain. 35012346 10 30 theme human 1192:1196 arg1 cells 1224:1228 primary human cervical epithelial (Pex) cells 1184:1228 primary human cervical epithelial (Pex) cells 1184:1228 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 0 31 theme New 101:103 arg1 Insight 105:111 New Insight 101:111 New Insight into HIV Transmission in Women 101:142 Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women. 35012346 8 32 theme CR3 981:983 arg1 binding 985:991 CR3 binding 981:991 CR3 binding 981:991 Man5 pentasaccharide, representative of HIV N-glycans, could compete with HIV-1 for CR3 binding. 35012346 15 33 theme T 1946:1946 arg1 cells 1948:1952 CD4 T cells 1942:1952 CD4 T cells 1942:1952 How HIV traverses the epithelium to infect CD4 T cells in the submucosa is ill-defined. 35012346 11 34 theme Pex 1320:1322 arg1 cells 1324:1328 Pex cells 1320:1328 Pex cells 1320:1328 Using Pex cells in a Transwell model system, we show that, following transcytosis across an intact Pex cell monolayer, HIV-1 is able to infect TZM-bl reporter cells. 35012346 0 35 theme Complement 0:9 arg1 Receptor 11:18 Complement Receptor 3 0:20 Complement Receptor 3 0:20 Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women. 35012346 14 36 theme HIV 1884:1886 arg1 infection 1888:1896 HIV infection 1884:1896 HIV infection 1884:1896 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 12 37 theme HIV-CR3 1494:1500 arg1 interaction 1502:1512 the HIV-CR3 interaction 1490:1512 the HIV-CR3 interaction using antibodies, mannose-binding lectins, or CR3-binding small-molecule drugs 1490:1591 Targeting the HIV-CR3 interaction using antibodies, mannose-binding lectins, or CR3-binding small-molecule drugs blocked HIV transcytosis. 35012346 17 38 theme epithelial 2243:2252 arg1 cells 2254:2258 human primary cervical epithelial cells 2220:2258 human primary cervical epithelial cells 2220:2258 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 17 38 theme epithelial 2243:2252 arg1 adherence 2170:2178 HIV adherence 2166:2178 HIV adherence 2166:2178 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 11 39 theme intact 1406:1411 arg1 monolayer 1422:1430 an intact Pex cell monolayer 1403:1430 an intact Pex cell monolayer 1403:1430 Using Pex cells in a Transwell model system, we show that, following transcytosis across an intact Pex cell monolayer, HIV-1 is able to infect TZM-bl reporter cells. 35012346 10 40 theme Pex 1219:1221 arg1 cells 1224:1228 primary human cervical epithelial (Pex) cells 1184:1228 primary human cervical epithelial (Pex) cells 1184:1228 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 11 41 theme Transwell 1335:1343 arg1 system 1351:1356 a Transwell model system 1333:1356 a Transwell model system 1333:1356 Using Pex cells in a Transwell model system, we show that, following transcytosis across an intact Pex cell monolayer, HIV-1 is able to infect TZM-bl reporter cells. 35012346 10 42 theme epithelial 1207:1216 arg1 cells 1224:1228 primary human cervical epithelial (Pex) cells 1184:1228 primary human cervical epithelial (Pex) cells 1184:1228 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 0 43 theme HIV-1 31:35 arg1 Transcytosis 37:48 HIV-1 Transcytosis 31:48 HIV-1 Transcytosis 31:48 Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women. 35012346 6 44 theme HIV-1 787:791 arg1 glycans 802:808 HIV-1 N-linked glycans 787:808 HIV-1 N-linked glycans 787:808 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 9 45 theme CHO 1043:1045 arg1 cells 1047:1051 CHO cells 1043:1051 CHO cells 1043:1051 Using cellular assays, we show that HIV bound to CHO cells by a CR3-dependent mechanism. 35012346 3 46 theme cervical 457:464 arg1 epithelia 466:474 the cervical epithelia 453:474 the cervical epithelia to cause cervicitis 453:494 In women, the bacterium Neisseria gonorrhoeae uses CR3 to invade the cervical epithelia to cause cervicitis. 35012346 18 47 from role 2284:2287 arg1 cells 2311:2315 epithelial cells 2300:2315 epithelial cells in dually facilitating HIV-1 attachment and entry 2300:2365 This suggests a unique role for CR3 on epithelial cells in dually facilitating HIV-1 attachment and entry. 35012346 2 48 theme complement 329:338 arg1 receptor 340:347 complement receptor 3 329:349 complement receptor 3 (CR3) (integrin αMβ2 or CD11b/CD18) 329:385 Cervical epithelial cells express complement receptor 3 (CR3) (integrin αMβ2 or CD11b/CD18). 35012346 2 48 theme complement 329:338 arg1 CR3 352:354 CR3 352:354 CR3 352:354 Cervical epithelial cells express complement receptor 3 (CR3) (integrin αMβ2 or CD11b/CD18). 35012346 1 49 theme reproductive 206:217 arg1 tract 219:223 the female reproductive tract 195:223 the female reproductive tract 195:223 Transmission of HIV across the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells is not fully understood. 35012346 6 50 theme binding 762:768 arg1 region 718:723 the I-domain region 705:723 the I-domain region of the CR3 alpha subunit, CD11b, and binding 705:768 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 14 51 theme female 1834:1839 arg1 site 1875:1878 the primary site 1863:1878 the primary site for HIV infection 1863:1896 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 14 51 theme female 1834:1839 arg1 IMPORTANCE 1803:1812 IMPORTANCE 1803:1812 IMPORTANCE In women 1803:1821 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 14 51 theme female 1834:1839 arg1 tract 1854:1858 the lower female reproductive tract 1824:1858 the lower female reproductive tract 1824:1858 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 4 52 theme cervical 565:572 arg1 epithelia 574:582 the cervical epithelia 561:582 the cervical epithelia 561:582 We hypothesized that HIV may also use CR3 to transcytose across the cervical epithelia. 35012346 13 53 theme HIV-1 1695:1699 arg1 transmission 1701:1712 HIV-1 transmission 1695:1712 HIV-1 transmission 1695:1712 These studies indicate that CR3/Pex may constitute an efficient pathway for HIV-1 transmission in women and also demonstrate strategies that may prevent transmission via this pathway. 35012346 9 54 theme CR3-dependent 1058:1070 arg1 mechanism 1072:1080 a CR3-dependent mechanism 1056:1080 a CR3-dependent mechanism 1056:1080 Using cellular assays, we show that HIV bound to CHO cells by a CR3-dependent mechanism. 35012346 7 55 theme HIV 839:841 arg1 surface 843:849 the HIV surface 835:849 the HIV surface 835:849 Mannosylated glycans on the HIV surface were a high-affinity ligand for the I-domain. 35012346 8 56 theme Man5 897:900 arg1 representative 919:932 representative 919:932 representative of HIV N-glycans 919:949 Man5 pentasaccharide, representative of HIV N-glycans, could compete with HIV-1 for CR3 binding. 35012346 8 56 theme Man5 897:900 arg1 pentasaccharide 902:916 Man5 pentasaccharide 897:916 Man5 pentasaccharide 897:916 Man5 pentasaccharide, representative of HIV N-glycans, could compete with HIV-1 for CR3 binding. 35012346 5 57 theme HIV-1 604:608 arg1 strains 610:616 HIV-1 strains 604:616 HIV-1 strains 604:616 Here, we show that HIV-1 strains bound with high affinity to recombinant CR3 in biophysical assays. 35012346 1 58 theme subepithelial 235:247 arg1 cells 264:268 subepithelial CD4-positive T cells 235:268 subepithelial CD4-positive T cells 235:268 Transmission of HIV across the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells is not fully understood. 35012346 6 59 theme CD11b 751:755 arg1 region 718:723 the I-domain region 705:723 the I-domain region of the CR3 alpha subunit, CD11b, and binding 705:768 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 7 60 theme Mannosylated 811:822 arg1 glycans 824:830 Mannosylated glycans 811:830 Mannosylated glycans on the HIV surface 811:849 Mannosylated glycans on the HIV surface were a high-affinity ligand for the I-domain. 35012346 7 60 theme Mannosylated 811:822 arg1 ligand 872:877 a high-affinity ligand 856:877 a high-affinity ligand for the I-domain 856:894 Mannosylated glycans on the HIV surface were a high-affinity ligand for the I-domain. 35012346 1 61 theme T 262:262 arg1 cells 264:268 subepithelial CD4-positive T cells 235:268 subepithelial CD4-positive T cells 235:268 Transmission of HIV across the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells is not fully understood. 35012346 6 62 theme I-domain 709:716 arg1 region 718:723 the I-domain region 705:723 the I-domain region of the CR3 alpha subunit, CD11b, and binding 705:768 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 17 63 theme primary 2226:2232 arg1 cells 2254:2258 human primary cervical epithelial cells 2220:2258 human primary cervical epithelial cells 2220:2258 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 17 63 theme primary 2226:2232 arg1 adherence 2170:2178 HIV adherence 2166:2178 HIV adherence 2166:2178 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 6 64 theme subunit 742:748 arg1 region 718:723 the I-domain region 705:723 the I-domain region of the CR3 alpha subunit, CD11b, and binding 705:768 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 14 65 from IMPORTANCE 1803:1812 arg1 women 1817:1821 women 1817:1821 women 1817:1821 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 1 66 theme HIV 161:163 arg1 Transmission 145:156 Transmission 145:156 Transmission of HIV across the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells 145:268 Transmission of HIV across the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells is not fully understood. 35012346 8 67 theme N-glycans 941:949 arg1 representative 919:932 representative 919:932 representative of HIV N-glycans 919:949 Man5 pentasaccharide, representative of HIV N-glycans, could compete with HIV-1 for CR3 binding. 35012346 8 67 theme N-glycans 941:949 arg1 pentasaccharide 902:916 Man5 pentasaccharide 897:916 Man5 pentasaccharide 897:916 Man5 pentasaccharide, representative of HIV N-glycans, could compete with HIV-1 for CR3 binding. 35012346 6 68 theme CR3 732:734 arg1 subunit 742:748 the CR3 alpha subunit 728:748 the CR3 alpha subunit 728:748 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 16 69 contain have 2013:2016 arg2 CR3 2035:2037 a protein called CR3 2018:2037 a protein called CR3 2018:2037 Cervical epithelial cells have a protein called CR3 on their surface. 35012346 16 69 contain have 2013:2016 arg1 cells 2007:2011 Cervical epithelial cells 1987:2011 Cervical epithelial cells 1987:2011 Cervical epithelial cells have a protein called CR3 on their surface. 35012346 16 70 theme called 2028:2033 arg1 CR3 2035:2037 a protein called CR3 2018:2037 a protein called CR3 2018:2037 Cervical epithelial cells have a protein called CR3 on their surface. 35012346 0 71 theme HIV 118:120 arg1 Transmission 122:133 HIV Transmission 118:133 HIV Transmission in Women 118:142 Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women. 35012346 2 72 theme Cervical 295:302 arg1 cells 315:319 Cervical epithelial cells 295:319 Cervical epithelial cells 295:319 Cervical epithelial cells express complement receptor 3 (CR3) (integrin αMβ2 or CD11b/CD18). 35012346 5 73 theme biophysical 665:675 arg1 assays 677:682 biophysical assays 665:682 biophysical assays 665:682 Here, we show that HIV-1 strains bound with high affinity to recombinant CR3 in biophysical assays. 35012346 5 74 theme high 629:632 arg1 affinity 634:641 high affinity 629:641 high affinity 629:641 Here, we show that HIV-1 strains bound with high affinity to recombinant CR3 in biophysical assays. 35012346 10 75 theme HIV-1 1284:1288 arg1 adherence 1290:1298 HIV-1 adherence 1284:1298 HIV-1 adherence to Pex cells 1284:1311 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 17 76 theme HIV 2166:2168 arg1 cells 2254:2258 human primary cervical epithelial cells 2220:2258 human primary cervical epithelial cells 2220:2258 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 17 76 theme HIV 2166:2168 arg1 adherence 2170:2178 HIV adherence 2166:2178 HIV adherence 2166:2178 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 0 77 dep Mediates 22:29 arg1 Insight 105:111 New Insight 101:111 New Insight into HIV Transmission in Women 101:142 Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women. 35012346 19 78 theme intact 2513:2518 arg1 barrier 2540:2546 an intact cervical epithelial barrier 2510:2546 an intact cervical epithelial barrier 2510:2546 The HIV-CR3 interaction may constitute an efficient pathway for HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier. 35012346 10 79 theme envelope 1130:1137 arg1 glycoprotein 1139:1150 the HIV-1 envelope glycoprotein 1120:1150 the HIV-1 envelope glycoprotein 1120:1150 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 0 80 theme Cervical 67:74 arg1 Barrier 92:98 an Intact Cervical Epithelial Cell Barrier 57:98 an Intact Cervical Epithelial Cell Barrier 57:98 Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women. 35012346 12 81 theme HIV 1601:1603 arg1 transcytosis 1605:1616 HIV transcytosis 1601:1616 HIV transcytosis 1601:1616 Targeting the HIV-CR3 interaction using antibodies, mannose-binding lectins, or CR3-binding small-molecule drugs blocked HIV transcytosis. 35012346 11 82 theme TZM-bl 1457:1462 arg1 cells 1473:1477 TZM-bl reporter cells 1457:1477 TZM-bl reporter cells 1457:1477 Using Pex cells in a Transwell model system, we show that, following transcytosis across an intact Pex cell monolayer, HIV-1 is able to infect TZM-bl reporter cells. 35012346 10 83 theme CR3 1101:1103 arg1 I-domain 1105:1112 the CR3 I-domain 1097:1112 the CR3 I-domain 1097:1112 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 10 84 theme HIV-1 1175:1179 arg1 binding 1164:1170 the binding 1160:1170 the binding of HIV-1 to primary human cervical epithelial (Pex) cells 1160:1228 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 0 85 theme Cell 87:90 arg1 Barrier 92:98 an Intact Cervical Epithelial Cell Barrier 57:98 an Intact Cervical Epithelial Cell Barrier 57:98 Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women. 35012346 19 86 theme cervical 2520:2527 arg1 barrier 2540:2546 an intact cervical epithelial barrier 2510:2546 an intact cervical epithelial barrier 2510:2546 The HIV-CR3 interaction may constitute an efficient pathway for HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier. 35012346 12 87 theme CR3-binding 1560:1570 arg1 drugs 1587:1591 CR3-binding small-molecule drugs 1560:1591 CR3-binding small-molecule drugs 1560:1591 Targeting the HIV-CR3 interaction using antibodies, mannose-binding lectins, or CR3-binding small-molecule drugs blocked HIV transcytosis. 35012346 9 88 theme cellular 1000:1007 arg1 assays 1009:1014 cellular assays 1000:1014 cellular assays 1000:1014 Using cellular assays, we show that HIV bound to CHO cells by a CR3-dependent mechanism. 35012346 10 89 theme cervical 1198:1205 arg1 cells 1224:1228 primary human cervical epithelial (Pex) cells 1184:1228 primary human cervical epithelial (Pex) cells 1184:1228 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 15 90 theme CD4 1942:1944 arg1 cells 1948:1952 CD4 T cells 1942:1952 CD4 T cells 1942:1952 How HIV traverses the epithelium to infect CD4 T cells in the submucosa is ill-defined. 35012346 0 91 from Transmission 122:133 arg1 Women 138:142 Women 138:142 Women 138:142 Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women. 35012346 10 92 theme primary 1184:1190 arg1 cells 1224:1228 primary human cervical epithelial (Pex) cells 1184:1228 primary human cervical epithelial (Pex) cells 1184:1228 Antibodies to the CR3 I-domain or to the HIV-1 envelope glycoprotein blocked the binding of HIV-1 to primary human cervical epithelial (Pex) cells, indicating that CR3 was necessary and sufficient for HIV-1 adherence to Pex cells. 35012346 19 93 theme virus 2484:2488 arg1 transmission 2490:2501 virus transmission 2484:2501 virus transmission across an intact cervical epithelial barrier 2484:2546 The HIV-CR3 interaction may constitute an efficient pathway for HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier. 35012346 12 94 theme mannose-binding 1532:1546 arg1 lectins 1548:1554 mannose-binding lectins 1532:1554 mannose-binding lectins 1532:1554 Targeting the HIV-CR3 interaction using antibodies, mannose-binding lectins, or CR3-binding small-molecule drugs blocked HIV transcytosis. 35012346 17 95 theme cervical 2234:2241 arg1 cells 2254:2258 human primary cervical epithelial cells 2220:2258 human primary cervical epithelial cells 2220:2258 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 17 95 theme cervical 2234:2241 arg1 adherence 2170:2178 HIV adherence 2166:2178 HIV adherence 2166:2178 We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. 35012346 16 96 theme epithelial 1996:2005 arg1 cells 2007:2011 Cervical epithelial cells 1987:2011 Cervical epithelial cells 1987:2011 Cervical epithelial cells have a protein called CR3 on their surface. 35012346 11 97 theme model 1345:1349 arg1 system 1351:1356 a Transwell model system 1333:1356 a Transwell model system 1333:1356 Using Pex cells in a Transwell model system, we show that, following transcytosis across an intact Pex cell monolayer, HIV-1 is able to infect TZM-bl reporter cells. 35012346 2 98 theme integrin 358:365 arg1 αMβ2 367:370 integrin αMβ2 358:370 integrin αMβ2 358:370 Cervical epithelial cells express complement receptor 3 (CR3) (integrin αMβ2 or CD11b/CD18). 35012346 7 99 theme high-affinity 858:870 arg1 ligand 872:877 a high-affinity ligand 856:877 a high-affinity ligand for the I-domain 856:894 Mannosylated glycans on the HIV surface were a high-affinity ligand for the I-domain. 35012346 7 99 theme high-affinity 858:870 arg1 glycans 824:830 Mannosylated glycans 811:830 Mannosylated glycans on the HIV surface 811:849 Mannosylated glycans on the HIV surface were a high-affinity ligand for the I-domain. 35012346 6 100 theme bound 691:695 arg1 CR3 697:699 HIV-1 bound CR3 685:699 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding 685:768 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 2 101 dep receptor 340:347 arg1 CD11b/CD18 375:384 CD11b/CD18 375:384 CD11b/CD18 375:384 Cervical epithelial cells express complement receptor 3 (CR3) (integrin αMβ2 or CD11b/CD18). 35012346 2 101 dep receptor 340:347 arg1 αMβ2 367:370 integrin αMβ2 358:370 integrin αMβ2 358:370 Cervical epithelial cells express complement receptor 3 (CR3) (integrin αMβ2 or CD11b/CD18). 35012346 16 102 dep called 2028:2033 arg1 protein 2020:2026 protein 2020:2026 protein 2020:2026 Cervical epithelial cells have a protein called CR3 on their surface. 35012346 6 103 theme N-linked 793:800 arg1 glycans 802:808 HIV-1 N-linked glycans 787:808 HIV-1 N-linked glycans 787:808 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 14 104 theme primary 1867:1873 arg1 site 1875:1878 the primary site 1863:1878 the primary site for HIV infection 1863:1896 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 14 104 theme primary 1867:1873 arg1 IMPORTANCE 1803:1812 IMPORTANCE 1803:1812 IMPORTANCE In women 1803:1821 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 14 104 theme primary 1867:1873 arg1 tract 1854:1858 the lower female reproductive tract 1824:1858 the lower female reproductive tract 1824:1858 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 14 105 theme reproductive 1841:1852 arg1 site 1875:1878 the primary site 1863:1878 the primary site for HIV infection 1863:1896 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 14 105 theme reproductive 1841:1852 arg1 IMPORTANCE 1803:1812 IMPORTANCE 1803:1812 IMPORTANCE In women 1803:1821 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 14 105 theme reproductive 1841:1852 arg1 tract 1854:1858 the lower female reproductive tract 1824:1858 the lower female reproductive tract 1824:1858 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 6 106 theme HIV-1 685:689 arg1 CR3 697:699 HIV-1 bound CR3 685:699 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding 685:768 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 18 107 theme epithelial 2300:2309 arg1 cells 2311:2315 epithelial cells 2300:2315 epithelial cells in dually facilitating HIV-1 attachment and entry 2300:2365 This suggests a unique role for CR3 on epithelial cells in dually facilitating HIV-1 attachment and entry. 35012346 6 108 link N-linked 793:800 arg1 glycans 802:808 HIV-1 N-linked glycans 787:808 HIV-1 N-linked glycans 787:808 HIV-1 bound CR3 via the I-domain region of the CR3 alpha subunit, CD11b, and binding was dependent on HIV-1 N-linked glycans. 35012346 1 109 theme tract 219:223 arg1 surface 184:190 the mucosal surface 172:190 the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells 172:268 Transmission of HIV across the mucosal surface of the female reproductive tract to engage subepithelial CD4-positive T cells is not fully understood. 35012346 14 110 theme lower 1828:1832 arg1 site 1875:1878 the primary site 1863:1878 the primary site for HIV infection 1863:1896 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 14 110 theme lower 1828:1832 arg1 IMPORTANCE 1803:1812 IMPORTANCE 1803:1812 IMPORTANCE In women 1803:1821 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 14 110 theme lower 1828:1832 arg1 tract 1854:1858 the lower female reproductive tract 1824:1858 the lower female reproductive tract 1824:1858 IMPORTANCE In women, the lower female reproductive tract is the primary site for HIV infection. 35012346 20 111 with Strategies 2549:2558 arg1 potential 2565:2573 potential 2565:2573 potential 2565:2573 Strategies with potential to prevent transmission via this pathway are presented. 35012346 11 112 theme reporter 1464:1471 arg1 cells 1473:1477 TZM-bl reporter cells 1457:1477 TZM-bl reporter cells 1457:1477 Using Pex cells in a Transwell model system, we show that, following transcytosis across an intact Pex cell monolayer, HIV-1 is able to infect TZM-bl reporter cells. 33735218 5 0 theme CD4+ 829:832 arg1 responses 845:853 antigen-specific CD4+ and CD8+ T responses 812:853 antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency 812:932 We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. 33735218 7 1 link O-linked 1079:1086 arg1 glycans 1088:1094 O-linked glycans 1079:1094 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa 1079:1148 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 3 2 theme essential 554:562 arg1 component 564:572 an essential component 551:572 an essential component of the resolution of fungal pathogens 551:610 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 3 2 theme essential 554:562 arg1 immunity 539:546 cellular immunity 530:546 cellular immunity 530:546 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 3 3 theme antibody 377:384 arg1 contribution 361:372 the contribution 357:372 the contribution of antibody to host defense 357:400 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 6 4 theme mucosal 984:990 arg1 vaccination 992:1002 successful systemic and mucosal vaccination 960:1002 successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection 960:1062 Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. 33735218 3 5 theme fungal 595:600 arg1 pathogens 602:610 fungal pathogens 595:610 fungal pathogens 595:610 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 4 6 theme potent 711:716 arg1 adjuvancy 718:726 potent adjuvancy 711:726 potent adjuvancy 711:726 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 6 7 theme systemic 971:978 arg1 vaccination 992:1002 successful systemic and mucosal vaccination 960:1002 successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection 960:1062 Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. 33735218 7 8 theme lethal 1219:1224 arg1 influenza 1226:1234 lethal influenza and fungal pulmonary challenge 1219:1265 influenza 1226:1234 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 3 9 theme pathogens 602:610 arg1 resolution 581:590 the resolution 577:590 the resolution of fungal pathogens 577:610 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 4 10 theme structural 635:644 arg1 bases 646:650 the structural bases 631:650 the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2) 631:765 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 5 11 theme developmental 789:801 arg1 steps 803:807 the developmental steps 785:807 the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency 785:932 We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. 33735218 6 12 theme successful 960:969 arg1 vaccination 992:1002 successful systemic and mucosal vaccination 960:1002 successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection 960:1062 Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. 33735218 4 13 gly glycoprotein 674:685 arg1 glycoprotein 674:685 a newly identified glycoprotein ligand 655:692 a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy 655:726 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 3 14 theme resolution 581:590 arg1 component 564:572 an essential component 551:572 an essential component of the resolution of fungal pathogens 551:610 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 3 14 theme resolution 581:590 arg1 immunity 539:546 cellular immunity 530:546 cellular immunity 530:546 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 1 15 theme non-replicating 185:199 arg1 antigens 215:222 non-replicating protein-based antigens 185:222 non-replicating protein-based antigens 185:222 The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. 33735218 7 16 theme fungal 1240:1245 arg1 challenge 1257:1265 lethal influenza and fungal pulmonary challenge 1219:1265 challenge 1257:1265 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 3 17 theme infectious 436:445 arg1 diseases 447:454 infectious diseases 436:454 infectious diseases such as fungi 436:468 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 3 17 theme infectious 436:445 arg1 fungi 464:468 fungi 464:468 fungi 464:468 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 1 18 theme protein-based 201:213 arg1 antigens 215:222 non-replicating protein-based antigens 185:222 non-replicating protein-based antigens 185:222 The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. 33735218 7 19 theme subunit- 1174:1181 arg1 immunity 1202:1209 vaccine subunit- induced protective immunity 1166:1209 vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge 1166:1265 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 1 20 theme antigens 215:222 arg1 immunogenicity 167:180 immunogenicity 167:180 immunogenicity of non-replicating protein-based antigens 167:222 The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. 33735218 0 21 theme Structural 0:9 arg1 basis 11:15 Structural basis 0:15 Structural basis of Blastomyces Endoglucanase-2 0:46 Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. 33735218 7 22 theme induced 1183:1189 arg1 immunity 1202:1209 vaccine subunit- induced protective immunity 1166:1209 vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge 1166:1265 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 7 23 theme protective 1191:1200 arg1 immunity 1202:1209 vaccine subunit- induced protective immunity 1166:1209 vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge 1166:1265 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 7 24 from glycans 1088:1094 arg1 Bl-Eng2 1099:1105 Bl-Eng2 1099:1105 Bl-Eng2 applied at the skin and respiratory mucosa 1099:1148 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 3 25 theme certain 417:423 arg1 classes 425:431 certain classes 417:431 certain classes of infectious diseases such as fungi 417:468 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 5 26 theme responses 845:853 arg1 steps 803:807 the developmental steps 785:807 the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency 785:932 We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. 33735218 4 27 theme ligand 687:692 arg1 bases 646:650 the structural bases 631:650 the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2) 631:765 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 6 28 theme A 1052:1052 arg1 infection 1054:1062 Influenza A infection 1042:1062 Influenza A infection 1042:1062 Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. 33735218 7 29 theme vaccine 1166:1172 arg1 immunity 1202:1209 vaccine subunit- induced protective immunity 1166:1209 vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge 1166:1265 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 1 30 theme safe 113:116 arg1 vaccines 126:133 safe subunit vaccines 113:133 safe subunit vaccines 113:133 The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. 33735218 4 31 theme glycoprotein 674:685 arg1 ligand 687:692 a newly identified glycoprotein ligand 655:692 a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy 655:726 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 4 31 theme glycoprotein 674:685 arg1 endoglucanase-2 741:755 Blastomyces endoglucanase-2 729:755 Blastomyces endoglucanase-2 (Bl-Eng2) 729:765 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 5 32 theme CD8+ 838:841 arg1 responses 845:853 antigen-specific CD4+ and CD8+ T responses 812:853 antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency 812:932 We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. 33735218 6 33 theme Influenza 1042:1050 arg1 infection 1054:1062 Influenza A infection 1042:1062 Influenza A infection 1042:1062 Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. 33735218 6 34 theme Dectin-2 935:942 arg1 ligation 944:951 Dectin-2 ligation 935:951 Dectin-2 ligation 935:951 Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. 33735218 2 35 theme protective 292:301 arg1 antibodies 303:312 protective antibodies 292:312 protective antibodies driven by adjuvants such as alum 292:345 Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. 33735218 4 36 theme Dectin-2 697:704 arg1 ligand 687:692 a newly identified glycoprotein ligand 655:692 a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy 655:726 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 4 36 theme Dectin-2 697:704 arg1 endoglucanase-2 741:755 Blastomyces endoglucanase-2 729:755 Blastomyces endoglucanase-2 (Bl-Eng2) 729:765 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 0 37 theme Endoglucanase-2 32:46 arg1 basis 11:15 Structural basis 0:15 Structural basis of Blastomyces Endoglucanase-2 0:46 Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. 33735218 5 38 theme T 843:843 arg1 responses 845:853 antigen-specific CD4+ and CD8+ T responses 812:853 antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency 812:932 We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. 33735218 0 39 theme Blastomyces 20:30 arg1 Endoglucanase-2 32:46 Blastomyces Endoglucanase-2 20:46 Blastomyces Endoglucanase-2 20:46 Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. 33735218 5 40 theme tissue 917:922 arg1 residency 924:932 tissue residency 917:932 tissue residency 917:932 We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. 33735218 3 41 theme clinical 498:505 arg1 observations 507:518 clinical observations 498:518 clinical observations 498:518 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 3 42 theme diseases 447:454 arg1 classes 425:431 certain classes 417:431 certain classes of infectious diseases such as fungi 417:468 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 3 43 theme host 389:392 arg1 defense 394:400 host defense 389:400 host defense 389:400 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 1 44 theme subunit 118:124 arg1 vaccines 126:133 safe subunit vaccines 113:133 safe subunit vaccines 113:133 The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. 33735218 7 45 theme pulmonary 1247:1255 arg1 challenge 1257:1265 lethal influenza and fungal pulmonary challenge 1219:1265 challenge 1257:1265 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 6 46 theme fungal 1021:1026 arg1 infection 1028:1036 invasive fungal infection 1012:1036 invasive fungal infection 1012:1036 Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. 33735218 7 47 theme respiratory 1131:1141 arg1 mucosa 1143:1148 respiratory mucosa 1131:1148 respiratory mucosa 1131:1148 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 2 48 theme infectious 250:259 arg1 diseases 261:268 infectious diseases 250:268 infectious diseases 250:268 Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. 33735218 1 49 theme vaccines 126:133 arg1 development 98:108 The development 94:108 The development of safe subunit vaccines 94:133 The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. 33735218 3 50 theme animal 479:484 arg1 studies 486:492 animal studies 479:492 animal studies 479:492 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 6 51 theme invasive 1012:1019 arg1 infection 1028:1036 invasive fungal infection 1012:1036 invasive fungal infection 1012:1036 Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. 33735218 3 52 dep limited 405:411 arg1 whereas 471:477 whereas 471:477 whereas 471:477 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 5 53 theme antigen-specific 812:827 arg1 responses 845:853 antigen-specific CD4+ and CD8+ T responses 812:853 antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency 812:932 We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. 33735218 3 54 theme cellular 530:537 arg1 component 564:572 an essential component 551:572 an essential component of the resolution of fungal pathogens 551:610 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 3 54 theme cellular 530:537 arg1 immunity 539:546 cellular immunity 530:546 cellular immunity 530:546 However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. 33735218 4 55 with ligand 687:692 arg1 adjuvancy 718:726 potent adjuvancy 711:726 potent adjuvancy 711:726 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 7 56 theme O-linked 1079:1086 arg1 glycans 1088:1094 O-linked glycans 1079:1094 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa 1079:1148 O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge. 33735218 0 57 theme -viral 77:82 arg1 immunity 84:91 anti-fungal and -viral immunity 61:91 anti-fungal and -viral immunity 61:91 Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. 33735218 2 58 theme Current 225:231 arg1 vaccines 233:240 Current vaccines 225:240 Current vaccines against infectious diseases 225:268 Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. 33735218 4 59 theme identified 663:672 arg1 ligand 687:692 a newly identified glycoprotein ligand 655:692 a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy 655:726 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 4 59 theme identified 663:672 arg1 endoglucanase-2 741:755 Blastomyces endoglucanase-2 729:755 Blastomyces endoglucanase-2 (Bl-Eng2) 729:765 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 0 60 theme anti-fungal 61:71 arg1 immunity 84:91 anti-fungal and -viral immunity 61:91 anti-fungal and -viral immunity 61:91 Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. 33735218 4 61 theme Blastomyces 729:739 arg1 Bl-Eng2 758:764 Bl-Eng2 758:764 Bl-Eng2 758:764 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 4 61 theme Blastomyces 729:739 arg1 endoglucanase-2 741:755 Blastomyces endoglucanase-2 729:755 Blastomyces endoglucanase-2 (Bl-Eng2) 729:765 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33735218 4 61 theme Blastomyces 729:739 arg1 ligand 687:692 a newly identified glycoprotein ligand 655:692 a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy 655:726 Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). 33741926 4 0 theme surface 628:634 arg1 N-glycans 644:652 surface mannose N-glycans 628:652 surface mannose N-glycans 628:652 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 2 1 theme high 302:305 arg1 Man5-9GlcNAc2 326:338 Man5-9GlcNAc2 326:338 Man5-9GlcNAc2 326:338 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 33741926 2 1 theme high 302:305 arg1 N-glycans 315:323 high mannose N-glycans 302:323 high mannose N-glycans (Man5-9GlcNAc2) 302:339 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 33741926 6 2 theme glycans 974:980 arg1 Recognition 929:939 Recognition 929:939 Recognition of surface N-linked high mannose glycans as a response to cellular stress 929:1013 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 6 2 theme glycans 974:980 arg1 mechanism 1030:1038 a molecular mechanism 1018:1038 a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait 1018:1147 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 0 3 theme cell 68:71 arg1 anaemia 73:79 sickle cell anaemia 61:79 sickle cell anaemia 61:79 Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance. 33741926 6 4 link N-linked 952:959 arg1 glycans 974:980 surface N-linked high mannose glycans 944:980 surface N-linked high mannose glycans 944:980 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 4 5 theme mannose 636:642 arg1 N-glycans 644:652 surface mannose N-glycans 628:652 surface mannose N-glycans 628:652 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 1 6 theme receptor-ligand 205:219 arg1 pairs 221:225 receptor-ligand pairs 205:225 receptor-ligand pairs mediating uptake 205:242 In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. 33741926 0 7 theme malaria 85:91 arg1 resistance 93:102 malaria resistance 85:102 malaria resistance 85:102 Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance. 33741926 4 8 theme hemoglobin 773:782 arg1 S 784:784 hemoglobin S 773:784 hemoglobin S 773:784 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 5 9 theme weight 834:839 arg1 complexes 841:849 high molecular weight complexes 819:849 high molecular weight complexes 819:849 The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. 33741926 4 10 theme Plasmodium 585:594 arg1 RBCs 616:619 Plasmodium falciparum-infected RBCs 585:619 Plasmodium falciparum-infected RBCs 585:619 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 6 11 theme high 961:964 arg1 glycans 974:980 surface N-linked high mannose glycans 944:980 surface N-linked high mannose glycans 944:980 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 5 12 theme weight 891:896 arg1 fragments 898:906 protease-resistant, lower molecular weight fragments 855:906 protease-resistant, lower molecular weight fragments containing spectrin 855:926 The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. 33741926 6 13 theme severe 1113:1118 arg1 malaria 1120:1126 severe malaria 1113:1126 severe malaria in sickle cell trait 1113:1147 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 6 14 theme cell 1138:1141 arg1 trait 1143:1147 sickle cell trait 1131:1147 sickle cell trait 1131:1147 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 4 15 theme infected 701:708 arg1 RBCs 710:713 infected RBCs 701:713 infected RBCs from sickle cell trait subjects 701:745 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 6 16 theme sickle 1075:1080 arg1 disease 1087:1093 sickle cell disease 1075:1093 sickle cell disease 1075:1093 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 4 17 theme sickle 720:725 arg1 subjects 738:745 sickle cell trait subjects 720:745 sickle cell trait subjects 720:745 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 1 18 theme red 146:148 arg1 cells 156:160 red blood cells 146:160 red blood cells (RBCs) 146:167 In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. 33741926 1 18 theme red 146:148 arg1 RBCs 163:166 RBCs 163:166 RBCs 163:166 In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. 33741926 6 19 theme N-linked 952:959 arg1 glycans 974:980 surface N-linked high mannose glycans 944:980 surface N-linked high mannose glycans 944:980 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 2 20 from receptor 407:414 arg1 phagocytes 427:436 phagocytes 427:436 phagocytes 427:436 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 33741926 1 21 theme blood 150:154 arg1 cells 156:160 red blood cells 146:160 red blood cells (RBCs) 146:167 In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. 33741926 1 21 theme blood 150:154 arg1 RBCs 163:166 RBCs 163:166 RBCs 163:166 In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. 33741926 0 22 theme blood 4:8 arg1 cell 10:13 Red blood cell 0:13 Red blood cell 0:13 Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance. 33741926 4 23 from levels 691:696 arg1 RBCs 710:713 infected RBCs 701:713 infected RBCs from sickle cell trait subjects 701:745 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 4 24 theme higher 684:689 arg1 levels 691:696 significantly higher levels 670:696 significantly higher levels on infected RBCs from sickle cell trait subjects 670:745 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 3 25 from levels 556:561 arg1 RBCs 566:569 RBCs 566:569 RBCs 566:569 We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. 33741926 0 26 theme Red 0:2 arg1 cell 10:13 Red blood cell 0:13 Red blood cell 0:13 Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance. 33741926 6 27 theme surface 944:950 arg1 glycans 974:980 surface N-linked high mannose glycans 944:980 surface N-linked high mannose glycans 944:980 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 3 28 theme sickle 500:505 arg1 disease 512:518 sickle cell disease 500:518 sickle cell disease 500:518 We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. 33741926 4 29 theme falciparum-infected 596:614 arg1 RBCs 616:619 Plasmodium falciparum-infected RBCs 585:619 Plasmodium falciparum-infected RBCs 585:619 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 2 30 theme RBC 376:378 arg1 surfaces 380:387 diseased or oxidized RBC surfaces 355:387 diseased or oxidized RBC surfaces 355:387 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 33741926 3 31 theme extravascular 473:485 arg1 hemolysis 487:495 extravascular hemolysis 473:495 extravascular hemolysis in sickle cell disease 473:518 We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. 33741926 5 32 contain containing 908:917 arg2 spectrin 919:926 spectrin 919:926 spectrin 919:926 The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. 33741926 5 32 contain containing 908:917 arg1 fragments 898:906 protease-resistant, lower molecular weight fragments 855:906 protease-resistant, lower molecular weight fragments containing spectrin 855:926 The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. 33741926 2 33 theme oxidized 367:374 arg1 surfaces 380:387 diseased or oxidized RBC surfaces 355:387 diseased or oxidized RBC surfaces 355:387 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 33741926 5 34 dep protease-resistant 855:872 arg1 molecular 881:889 molecular 881:889 molecular 881:889 The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. 33741926 6 35 from malaria 1120:1126 arg1 trait 1143:1147 sickle cell trait 1131:1147 sickle cell trait 1131:1147 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 2 36 theme diseased 355:362 arg1 surfaces 380:387 diseased or oxidized RBC surfaces 355:387 diseased or oxidized RBC surfaces 355:387 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 33741926 0 37 theme phagocytic 27:36 arg1 ligands 38:44 phagocytic ligands 27:44 phagocytic ligands mediating both sickle cell anaemia and malaria resistance 27:102 Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance. 33741926 5 38 theme high 819:822 arg1 complexes 841:849 high molecular weight complexes 819:849 high molecular weight complexes 819:849 The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. 33741926 2 39 theme mannose 399:405 arg1 CD206 417:421 CD206 417:421 CD206 417:421 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 33741926 2 39 theme mannose 399:405 arg1 receptor 407:414 the mannose receptor 395:414 the mannose receptor (CD206) on phagocytes to mediate clearance 395:457 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 33741926 6 40 theme mannose 966:972 arg1 glycans 974:980 surface N-linked high mannose glycans 944:980 surface N-linked high mannose glycans 944:980 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 6 41 theme cellular 999:1006 arg1 stress 1008:1013 cellular stress 999:1013 cellular stress 999:1013 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 5 42 theme molecular 824:832 arg1 complexes 841:849 high molecular weight complexes 819:849 high molecular weight complexes 819:849 The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. 33741926 3 43 theme cell 507:510 arg1 disease 512:518 sickle cell disease 500:518 sickle cell disease 500:518 We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. 33741926 5 44 theme protease-resistant 855:872 arg1 fragments 898:906 protease-resistant, lower molecular weight fragments 855:906 protease-resistant, lower molecular weight fragments containing spectrin 855:926 The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. 33741926 6 45 theme molecular 1020:1028 arg1 mechanism 1030:1038 a molecular mechanism 1018:1038 a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait 1018:1147 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 6 45 theme molecular 1020:1028 arg1 Recognition 929:939 Recognition 929:939 Recognition of surface N-linked high mannose glycans as a response to cellular stress 929:1013 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 6 46 theme disease 1087:1093 arg1 pathogenesis 1059:1070 the pathogenesis 1055:1070 the pathogenesis of sickle cell disease 1055:1093 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 6 46 theme disease 1087:1093 arg1 resistance 1099:1108 resistance 1099:1108 resistance to severe malaria in sickle cell trait 1099:1147 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 4 47 theme trait 732:736 arg1 subjects 738:745 sickle cell trait subjects 720:745 sickle cell trait subjects 720:745 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 3 48 theme glycan 549:554 arg1 levels 556:561 high mannose glycan levels 536:561 high mannose glycan levels on RBCs 536:569 We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. 33741926 1 49 theme sickle 113:118 arg1 disease 125:131 sickle cell disease 113:131 sickle cell disease 113:131 In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. 33741926 3 50 from hemolysis 487:495 arg1 disease 512:518 sickle cell disease 500:518 sickle cell disease 500:518 We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. 33741926 4 51 theme cell 727:730 arg1 subjects 738:745 sickle cell trait subjects 720:745 sickle cell trait subjects 720:745 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 6 52 theme sickle 1131:1136 arg1 trait 1143:1147 sickle cell trait 1131:1147 sickle cell trait 1131:1147 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 1 53 theme cell 120:123 arg1 disease 125:131 sickle cell disease 113:131 sickle cell disease 113:131 In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. 33741926 6 54 theme cell 1082:1085 arg1 disease 1087:1093 sickle cell disease 1075:1093 sickle cell disease 1075:1093 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 0 55 theme sickle 61:66 arg1 anaemia 73:79 sickle cell anaemia 61:79 sickle cell anaemia 61:79 Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance. 33741926 3 56 theme high 536:539 arg1 levels 556:561 high mannose glycan levels 536:561 high mannose glycan levels on RBCs 536:569 We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. 33741926 4 57 from subjects 738:745 arg1 RBCs 710:713 infected RBCs 701:713 infected RBCs from sickle cell trait subjects 701:745 Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. 33741926 2 58 theme N-glycans 315:323 arg1 patches 291:297 patches 291:297 patches 291:297 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 33741926 6 59 theme common 1040:1045 arg1 mechanism 1030:1038 a molecular mechanism 1018:1038 a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait 1018:1147 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 6 59 theme common 1040:1045 arg1 Recognition 929:939 Recognition 929:939 Recognition of surface N-linked high mannose glycans as a response to cellular stress 929:1013 Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. 33741926 3 60 theme mannose 541:547 arg1 levels 556:561 high mannose glycan levels 536:561 high mannose glycan levels on RBCs 536:569 We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. 33741926 2 61 theme mannose 307:313 arg1 Man5-9GlcNAc2 326:338 Man5-9GlcNAc2 326:338 Man5-9GlcNAc2 326:338 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 33741926 2 61 theme mannose 307:313 arg1 N-glycans 315:323 high mannose N-glycans 302:323 high mannose N-glycans (Man5-9GlcNAc2) 302:339 Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. 35612312 6 0 theme improved 1095:1102 arg1 switching 1126:1134 improved IgG1-to-IgG2a isotype switching 1095:1134 improved IgG1-to-IgG2a isotype switching 1095:1134 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 4 1 theme sequence 545:552 arg1 layer 533:537 the front layer 523:537 the front layer of E2 sequence 523:552 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 10 2 theme proinflammatory 1966:1980 arg1 response 1982:1989 improved proinflammatory response 1957:1989 improved proinflammatory response 1957:1989 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 1 3 theme adaptive 225:232 arg1 responses 241:249 innate and adaptive immune responses 214:249 innate and adaptive immune responses 214:249 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 35612312 7 4 theme vaccine 1530:1536 arg1 development 1538:1548 HCV vaccine development 1526:1548 HCV vaccine development 1526:1548 Further investigation of the modified E2 antigen may provide helpful information for HCV vaccine development. 35612312 11 5 theme immune 2195:2200 arg1 responses 2202:2210 robust protective immune responses 2177:2210 robust protective immune responses 2177:2210 The results clearly suggested that HCV E2 exhibits immunoregulatory activity that inhibits induction of robust protective immune responses. 35612312 7 6 theme antigen 1482:1488 arg1 investigation 1449:1461 Further investigation 1441:1461 Further investigation of the modified E2 antigen 1441:1488 Further investigation of the modified E2 antigen may provide helpful information for HCV vaccine development. 35612312 1 7 theme responses 241:249 arg1 impairment 200:209 an impairment 197:209 an impairment of innate and adaptive immune responses 197:249 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 35612312 1 8 theme C 123:123 arg1 HCV 132:134 HCV 132:134 HCV 132:134 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 35612312 1 8 theme C 123:123 arg1 virus 125:129 Hepatitis C virus 113:129 Hepatitis C virus (HCV) 113:135 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 35612312 9 9 theme soluble 1713:1719 arg1 E2 1721:1722 soluble E2 1713:1722 soluble E2 (sE2) 1713:1728 We have identified that an alteration of amino acids in the front layer of soluble E2 (sE2) disrupts CD81 interaction and alters the cytokine response. 35612312 9 9 theme soluble 1713:1719 arg1 sE2 1725:1727 sE2 1725:1727 sE2 1725:1727 We have identified that an alteration of amino acids in the front layer of soluble E2 (sE2) disrupts CD81 interaction and alters the cytokine response. 35612312 6 10 theme pseudotype 1188:1197 arg1 virus 1199:1203 HCV pseudotype virus 1184:1203 HCV pseudotype virus 1184:1203 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 4 11 theme immunogen 621:629 arg1 candidate 649:657 an HCV vaccine candidate 634:657 an HCV vaccine candidate 634:657 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 4 11 theme immunogen 621:629 arg1 potential 594:602 the potential 590:602 the potential of the resulting immunogen 590:629 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 0 12 theme Modified 0:7 arg1 Glycoprotein 12:23 Modified E2 Glycoprotein 0:23 Modified E2 Glycoprotein of Hepatitis C Virus 0:44 Modified E2 Glycoprotein of Hepatitis C Virus Enhances Proinflammatory Cytokines and Protective Immune Response. 35612312 1 13 theme high 159:162 arg1 number 164:169 a high number 157:169 a high number of chronic cases owing to an impairment of innate and adaptive immune responses 157:249 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 35612312 7 14 theme helpful 1502:1508 arg1 information 1510:1520 helpful information 1502:1520 helpful information for HCV vaccine development 1502:1548 Further investigation of the modified E2 antigen may provide helpful information for HCV vaccine development. 35612312 12 15 theme antigen 2240:2246 arg1 Selection 2213:2221 Selection 2213:2221 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations 2213:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 10 16 theme challenge 2048:2056 arg1 model 2058:2062 a surrogate HCV vaccinia challenge model 2023:2062 a surrogate HCV vaccinia challenge model 2023:2062 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 6 17 theme neutralizing 1152:1163 arg1 antibodies 1165:1174 neutralizing antibodies 1152:1174 neutralizing antibodies against HCV pseudotype virus 1152:1203 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 10 18 theme HCV 2035:2037 arg1 model 2058:2062 a surrogate HCV vaccinia challenge model 2023:2062 a surrogate HCV vaccinia challenge model 2023:2062 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 5 19 theme modified 664:671 arg1 F442NYT 686:692 F442NYT 686:692 F442NYT 686:692 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 5 19 theme modified 664:671 arg1 protein 677:683 The modified sE2 protein 660:683 The modified sE2 protein (F442NYT) 660:693 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 2 20 theme cell 264:267 arg1 surface 269:275 the cell surface 260:275 the cell surface 260:275 CD81 on the cell surface facilitates HCV entry by interacting with the E2 envelope glycoprotein. 35612312 5 21 theme higher 778:783 arg1 levels 785:790 higher levels 778:790 higher levels of proinflammatory cytokines 778:819 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 10 22 from efficacy 2006:2013 arg1 mice 2067:2070 mice 2067:2070 mice 2067:2070 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 9 23 theme CD81 1739:1742 arg1 interaction 1744:1754 CD81 interaction 1739:1754 CD81 interaction 1739:1754 We have identified that an alteration of amino acids in the front layer of soluble E2 (sE2) disrupts CD81 interaction and alters the cytokine response. 35612312 6 24 theme virus-expressing 1337:1352 arg1 model 1387:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 10 25 theme potential 1847:1855 arg1 site 1880:1883 an added potential N-linked glycosylation site 1838:1883 an added potential N-linked glycosylation site 1838:1883 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 11 26 theme HCV 2108:2110 arg1 E2 2112:2113 HCV E2 2108:2113 HCV E2 2108:2113 The results clearly suggested that HCV E2 exhibits immunoregulatory activity that inhibits induction of robust protective immune responses. 35612312 11 27 theme robust 2177:2182 arg1 responses 2202:2210 robust protective immune responses 2177:2210 robust protective immune responses 2177:2210 The results clearly suggested that HCV E2 exhibits immunoregulatory activity that inhibits induction of robust protective immune responses. 35612312 6 28 theme proliferative 1221:1233 arg1 response 1235:1242 a B and T cell proliferative response 1206:1242 response 1235:1242 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 10 29 dep sE2F442NYT 1817:1826 arg1 reduces 1889:1895 reduces 1889:1895 reduces CD81 binding activity 1889:1917 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 10 29 dep sE2F442NYT 1817:1826 arg1 includes 1829:1836 includes 1829:1836 includes an added potential N-linked glycosylation site 1829:1883 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 6 30 theme recombinant 1316:1326 arg1 model 1387:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 2 31 from CD81 252:255 arg1 surface 269:275 the cell surface 260:275 the cell surface 260:275 CD81 on the cell surface facilitates HCV entry by interacting with the E2 envelope glycoprotein. 35612312 6 32 with Immunization 970:981 arg1 vaccine 1075:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 6 33 theme T 1214:1214 arg1 response 1235:1242 a B and T cell proliferative response 1206:1242 response 1235:1242 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 5 34 theme antigen-presenting 902:919 arg1 cells 921:925 antigen-presenting cells 902:925 antigen-presenting cells 902:925 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 4 35 theme vaccine 641:647 arg1 candidate 649:657 an HCV vaccine candidate 634:657 an HCV vaccine candidate 634:657 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 4 35 theme vaccine 641:647 arg1 potential 594:602 the potential 590:602 the potential of the resulting immunogen 590:629 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 6 36 from response 1235:1242 arg1 antibodies 1165:1174 neutralizing antibodies 1152:1174 neutralizing antibodies against HCV pseudotype virus 1152:1203 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 10 37 link N-linked 1857:1864 arg1 site 1880:1883 an added potential N-linked glycosylation site 1838:1883 an added potential N-linked glycosylation site 1838:1883 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 5 38 theme unmodified 703:712 arg1 sE2 714:716 unmodified sE2 703:716 unmodified sE2 703:716 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 10 39 theme glycosylation 1866:1878 arg1 site 1880:1883 an added potential N-linked glycosylation site 1838:1883 an added potential N-linked glycosylation site 1838:1883 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 6 40 theme mice 993:996 arg1 Immunization 970:981 Immunization 970:981 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 970:1081 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 8 41 theme IMPORTANCE 1551:1560 arg1 HCV 1581:1583 HCV 1581:1583 HCV 1581:1583 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. 35612312 8 41 theme IMPORTANCE 1551:1560 arg1 virus 1574:1578 IMPORTANCE Hepatitis C virus 1551:1578 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding 1551:1600 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. 35612312 6 42 theme sE2 1419:1421 arg1 vaccine 1432:1438 E1/unmodified sE2 mRNA-LNP vaccine 1405:1438 E1/unmodified sE2 mRNA-LNP vaccine 1405:1438 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 12 43 from antigen 2240:2246 arg1 platform 2263:2270 an mRNA-LNP platform 2251:2270 an mRNA-LNP platform amenable to nucleic acid sequence alterations 2251:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 5 44 theme primary 862:868 arg1 macrophages 887:897 primary monocyte-derived macrophages 862:897 primary monocyte-derived macrophages as antigen-presenting cells 862:925 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 8 45 theme C 1572:1572 arg1 HCV 1581:1583 HCV 1581:1583 HCV 1581:1583 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. 35612312 8 45 theme C 1572:1572 arg1 virus 1574:1578 IMPORTANCE Hepatitis C virus 1551:1578 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding 1551:1600 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. 35612312 12 46 theme novel 2329:2333 arg1 approach 2335:2342 a novel approach 2327:2342 a novel approach for multigenotype HCV vaccine development 2327:2384 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 0 47 theme Immune 96:101 arg1 Response 103:110 Protective Immune Response 85:110 Protective Immune Response 85:110 Modified E2 Glycoprotein of Hepatitis C Virus Enhances Proinflammatory Cytokines and Protective Immune Response. 35612312 5 48 theme T 948:948 arg1 proliferation 955:967 CD4+ T cell proliferation 943:967 CD4+ T cell proliferation 943:967 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 12 49 theme multigenotype 2348:2360 arg1 development 2374:2384 multigenotype HCV vaccine development 2348:2384 multigenotype HCV vaccine development 2348:2384 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 12 50 from Selection 2213:2221 arg1 platform 2263:2270 an mRNA-LNP platform 2251:2270 an mRNA-LNP platform amenable to nucleic acid sequence alterations 2251:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 11 51 theme immunoregulatory 2124:2139 arg1 activity 2141:2148 immunoregulatory activity 2124:2148 immunoregulatory activity that inhibits induction of robust protective immune responses 2124:2210 The results clearly suggested that HCV E2 exhibits immunoregulatory activity that inhibits induction of robust protective immune responses. 35612312 12 52 theme vaccine 2366:2372 arg1 development 2374:2384 multigenotype HCV vaccine development 2348:2384 multigenotype HCV vaccine development 2348:2384 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 5 53 theme CD81 756:759 arg1 binding 761:767 CD81 binding 756:767 CD81 binding 756:767 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 6 54 theme mRNA-LNP 1065:1072 arg1 vaccine 1075:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 6 55 dep resulted 1083:1090 arg1 compared 1393:1400 compared 1393:1400 compared to E1/unmodified sE2 mRNA-LNP vaccine 1393:1438 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 7 56 theme modified 1470:1477 arg1 antigen 1482:1488 the modified E2 antigen 1466:1488 the modified E2 antigen 1466:1488 Further investigation of the modified E2 antigen may provide helpful information for HCV vaccine development. 35612312 1 57 theme Hepatitis 113:121 arg1 HCV 132:134 HCV 132:134 HCV 132:134 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 35612312 1 57 theme Hepatitis 113:121 arg1 virus 125:129 Hepatitis C virus 113:129 Hepatitis C virus (HCV) 113:135 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 35612312 6 58 theme nanoparticle 1051:1062 arg1 vaccine 1075:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 8 59 theme protective 1610:1619 arg1 response 1628:1635 protective immune response 1610:1635 protective immune response 1610:1635 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. 35612312 3 60 theme host 423:426 arg1 outcome 437:443 host response outcome 423:443 host response outcome to HCV infection 423:460 In addition, CD81/E2 binding on immunity-related cells may also influence host response outcome to HCV infection. 35612312 0 61 theme Hepatitis 28:36 arg1 Virus 40:44 Hepatitis C Virus 28:44 Hepatitis C Virus 28:44 Modified E2 Glycoprotein of Hepatitis C Virus Enhances Proinflammatory Cytokines and Protective Immune Response. 35612312 6 62 theme nucleoside-modified 1020:1038 arg1 vaccine 1075:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 3 63 theme CD81/E2 362:368 arg1 binding 370:376 CD81/E2 binding 362:376 CD81/E2 binding on immunity-related cells 362:402 In addition, CD81/E2 binding on immunity-related cells may also influence host response outcome to HCV infection. 35612312 4 64 theme amino 496:500 arg1 substitution 507:518 site-specific amino acid substitution 482:518 site-specific amino acid substitution 482:518 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 0 65 theme Proinflammatory 55:69 arg1 Cytokines 71:79 Proinflammatory Cytokines 55:79 Proinflammatory Cytokines 55:79 Modified E2 Glycoprotein of Hepatitis C Virus Enhances Proinflammatory Cytokines and Protective Immune Response. 35612312 12 66 theme acid 2292:2295 arg1 alterations 2306:2316 nucleic acid sequence alterations 2284:2316 nucleic acid sequence alterations 2284:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 6 67 from switching 1126:1134 arg1 antibodies 1165:1174 neutralizing antibodies 1152:1174 neutralizing antibodies against HCV pseudotype virus 1152:1203 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 0 68 theme Virus 40:44 arg1 Glycoprotein 12:23 Modified E2 Glycoprotein 0:23 Modified E2 Glycoprotein of Hepatitis C Virus 0:44 Modified E2 Glycoprotein of Hepatitis C Virus Enhances Proinflammatory Cytokines and Protective Immune Response. 35612312 3 69 theme HCV 448:450 arg1 infection 452:460 HCV infection 448:460 HCV infection 448:460 In addition, CD81/E2 binding on immunity-related cells may also influence host response outcome to HCV infection. 35612312 7 70 theme E2 1479:1480 arg1 antigen 1482:1488 the modified E2 antigen 1466:1488 the modified E2 antigen 1466:1488 Further investigation of the modified E2 antigen may provide helpful information for HCV vaccine development. 35612312 9 71 theme amino 1679:1683 arg1 acids 1685:1689 amino acids 1679:1689 amino acids 1679:1689 We have identified that an alteration of amino acids in the front layer of soluble E2 (sE2) disrupts CD81 interaction and alters the cytokine response. 35612312 4 72 theme CD81 564:567 arg1 binding 569:575 CD81 binding 564:575 CD81 binding 564:575 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 10 73 theme -mRNA-LNP 1919:1927 arg1 vaccine 1939:1945 modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine 1808:1945 modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine 1808:1945 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 5 74 theme cytokines 811:819 arg1 levels 785:790 higher levels 778:790 higher levels of proinflammatory cytokines 778:819 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 10 75 gly glycosylation 1866:1878 arg2 site 1880:1883 an added potential N-linked glycosylation site 1838:1883 an added potential N-linked glycosylation site 1838:1883 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 10 76 with Immunization 1790:1801 arg1 vaccine 1939:1945 modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine 1808:1945 modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine 1808:1945 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 6 77 theme IgG1-to-IgG2a 1104:1116 arg1 switching 1126:1134 improved IgG1-to-IgG2a isotype switching 1095:1134 improved IgG1-to-IgG2a isotype switching 1095:1134 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 6 78 theme mRNA-LNP 1423:1430 arg1 vaccine 1432:1438 E1/unmodified sE2 mRNA-LNP vaccine 1405:1438 E1/unmodified sE2 mRNA-LNP vaccine 1405:1438 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 2 79 theme E2 323:324 arg1 glycoprotein 335:346 the E2 envelope glycoprotein 319:346 the E2 envelope glycoprotein 319:346 CD81 on the cell surface facilitates HCV entry by interacting with the E2 envelope glycoprotein. 35612312 5 80 from reduction 743:751 arg1 binding 761:767 CD81 binding 756:767 CD81 binding 756:767 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 7 81 theme HCV 1526:1528 arg1 development 1538:1548 HCV vaccine development 1526:1548 HCV vaccine development 1526:1548 Further investigation of the modified E2 antigen may provide helpful information for HCV vaccine development. 35612312 9 82 theme front 1698:1702 arg1 layer 1704:1708 the front layer 1694:1708 the front layer of soluble E2 (sE2) 1694:1728 We have identified that an alteration of amino acids in the front layer of soluble E2 (sE2) disrupts CD81 interaction and alters the cytokine response. 35612312 10 83 theme CD81 1897:1900 arg1 activity 1910:1917 CD81 binding activity 1897:1917 CD81 binding activity 1897:1917 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 4 84 theme E2 542:543 arg1 sequence 545:552 E2 sequence 542:552 E2 sequence 542:552 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 1 85 theme cases 182:186 arg1 number 164:169 a high number 157:169 a high number of chronic cases owing to an impairment of innate and adaptive immune responses 157:249 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 35612312 10 86 theme improved 1957:1964 arg1 response 1982:1989 improved proinflammatory response 1957:1989 improved proinflammatory response 1957:1989 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 1 87 theme immune 234:239 arg1 responses 241:249 innate and adaptive immune responses 214:249 innate and adaptive immune responses 214:249 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 35612312 11 88 theme responses 2202:2210 arg1 induction 2164:2172 induction 2164:2172 induction of robust protective immune responses 2164:2210 The results clearly suggested that HCV E2 exhibits immunoregulatory activity that inhibits induction of robust protective immune responses. 35612312 6 89 theme improved 1261:1268 arg1 protection 1270:1279 improved protection 1261:1279 improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1261:1391 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 5 90 theme proinflammatory 795:809 arg1 cytokines 811:819 proinflammatory cytokines 795:819 proinflammatory cytokines 795:819 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 9 91 theme E2 1721:1722 arg1 layer 1704:1708 the front layer 1694:1708 the front layer of soluble E2 (sE2) 1694:1728 We have identified that an alteration of amino acids in the front layer of soluble E2 (sE2) disrupts CD81 interaction and alters the cytokine response. 35612312 6 92 theme HCV 1184:1186 arg1 virus 1199:1203 HCV pseudotype virus 1184:1203 HCV pseudotype virus 1184:1203 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 4 93 theme resulting 611:619 arg1 immunogen 621:629 the resulting immunogen 607:629 the resulting immunogen 607:629 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 10 94 theme protective 1995:2004 arg1 efficacy 2006:2013 protective efficacy 1995:2013 protective efficacy 1995:2013 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 2 95 theme HCV 289:291 arg1 entry 293:297 HCV entry 289:297 HCV entry 289:297 CD81 on the cell surface facilitates HCV entry by interacting with the E2 envelope glycoprotein. 35612312 8 96 theme virus 1574:1578 arg1 binding 1594:1600 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding 1551:1600 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding 1551:1600 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. 35612312 12 97 theme E2 2237:2238 arg1 antigen 2240:2246 engineered E2 antigen 2226:2246 engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations 2226:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 10 98 theme vaccinia 2039:2046 arg1 model 2058:2062 a surrogate HCV vaccinia challenge model 2023:2062 a surrogate HCV vaccinia challenge model 2023:2062 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 6 99 theme challenge 1377:1385 arg1 model 1387:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 10 100 theme sE2F442NYT 1817:1826 arg1 vaccine 1939:1945 modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine 1808:1945 modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine 1808:1945 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 1 101 theme chronic 174:180 arg1 cases 182:186 chronic cases 174:186 chronic cases owing to an impairment of innate and adaptive immune responses 174:249 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 35612312 10 102 from response 1982:1989 arg1 mice 2067:2070 mice 2067:2070 mice 2067:2070 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 10 103 theme surrogate 2025:2033 arg1 model 2058:2062 a surrogate HCV vaccinia challenge model 2023:2062 a surrogate HCV vaccinia challenge model 2023:2062 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 5 104 theme sE2 673:675 arg1 F442NYT 686:692 F442NYT 686:692 F442NYT 686:692 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 5 104 theme sE2 673:675 arg1 protein 677:683 The modified sE2 protein 660:683 The modified sE2 protein (F442NYT) 660:693 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 10 105 theme N-linked 1857:1864 arg1 site 1880:1883 an added potential N-linked glycosylation site 1838:1883 an added potential N-linked glycosylation site 1838:1883 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 6 106 theme vaccinia 1328:1335 arg1 model 1387:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 10 107 theme added 1841:1845 arg1 site 1880:1883 an added potential N-linked glycosylation site 1838:1883 an added potential N-linked glycosylation site 1838:1883 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 5 108 theme monocyte-derived 870:885 arg1 macrophages 887:897 primary monocyte-derived macrophages 862:897 primary monocyte-derived macrophages as antigen-presenting cells 862:925 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 11 109 theme protective 2184:2193 arg1 responses 2202:2210 robust protective immune responses 2177:2210 robust protective immune responses 2177:2210 The results clearly suggested that HCV E2 exhibits immunoregulatory activity that inhibits induction of robust protective immune responses. 35612312 6 110 theme cell 1216:1219 arg1 response 1235:1242 a B and T cell proliferative response 1206:1242 response 1235:1242 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 6 111 theme surrogate 1306:1314 arg1 model 1387:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 7 112 theme Further 1441:1447 arg1 investigation 1449:1461 Further investigation 1441:1461 Further investigation of the modified E2 antigen 1441:1488 Further investigation of the modified E2 antigen may provide helpful information for HCV vaccine development. 35612312 6 113 theme E1/sE2F442NYT 1006:1018 arg1 vaccine 1075:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 9 114 theme cytokine 1771:1778 arg1 response 1780:1787 the cytokine response 1767:1787 the cytokine response 1767:1787 We have identified that an alteration of amino acids in the front layer of soluble E2 (sE2) disrupts CD81 interaction and alters the cytokine response. 35612312 5 115 theme anti-inflammatory 832:848 arg1 response 850:857 anti-inflammatory response 832:857 anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells 832:925 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 8 116 theme Hepatitis 1562:1570 arg1 HCV 1581:1583 HCV 1581:1583 HCV 1581:1583 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. 35612312 8 116 theme Hepatitis 1562:1570 arg1 virus 1574:1578 IMPORTANCE Hepatitis C virus 1551:1578 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding 1551:1600 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. 35612312 4 117 theme HCV 637:639 arg1 candidate 649:657 an HCV vaccine candidate 634:657 an HCV vaccine candidate 634:657 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 4 117 theme HCV 637:639 arg1 potential 594:602 the potential 590:602 the potential of the resulting immunogen 590:629 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 6 118 from B 1208:1208 arg1 antibodies 1165:1174 neutralizing antibodies 1152:1174 neutralizing antibodies against HCV pseudotype virus 1152:1203 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 0 119 theme Protective 85:94 arg1 Response 103:110 Protective Immune Response 85:110 Protective Immune Response 85:110 Modified E2 Glycoprotein of Hepatitis C Virus Enhances Proinflammatory Cytokines and Protective Immune Response. 35612312 3 120 from binding 370:376 arg1 cells 398:402 immunity-related cells 381:402 immunity-related cells 381:402 In addition, CD81/E2 binding on immunity-related cells may also influence host response outcome to HCV infection. 35612312 6 121 theme BALB/c 986:991 arg1 mice 993:996 BALB/c mice 986:996 BALB/c mice 986:996 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 6 122 theme E1-E2-NS2aa134-966 1358:1375 arg1 model 1387:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 4 123 theme site-specific 482:494 arg1 substitution 507:518 site-specific amino acid substitution 482:518 site-specific amino acid substitution 482:518 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 6 124 theme E1/unmodified 1405:1417 arg1 vaccine 1432:1438 E1/unmodified sE2 mRNA-LNP vaccine 1405:1438 E1/unmodified sE2 mRNA-LNP vaccine 1405:1438 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 5 125 theme CD4+ 943:946 arg1 proliferation 955:967 CD4+ T cell proliferation 943:967 CD4+ T cell proliferation 943:967 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 10 126 theme modified 1808:1815 arg1 vaccine 1939:1945 modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine 1808:1945 modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine 1808:1945 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 12 127 theme HCV 2362:2364 arg1 development 2374:2384 multigenotype HCV vaccine development 2348:2384 multigenotype HCV vaccine development 2348:2384 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 5 128 from response 850:857 arg1 macrophages 887:897 primary monocyte-derived macrophages 862:897 primary monocyte-derived macrophages as antigen-presenting cells 862:925 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 5 129 theme cell 950:953 arg1 proliferation 955:967 CD4+ T cell proliferation 943:967 CD4+ T cell proliferation 943:967 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 8 130 theme E2-CD81 1586:1592 arg1 binding 1594:1600 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding 1551:1600 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding 1551:1600 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. 35612312 0 131 theme E2 9:10 arg1 Glycoprotein 12:23 Modified E2 Glycoprotein 0:23 Modified E2 Glycoprotein of Hepatitis C Virus 0:44 Modified E2 Glycoprotein of Hepatitis C Virus Enhances Proinflammatory Cytokines and Protective Immune Response. 35612312 6 132 theme HCV 1354:1356 arg1 model 1387:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 4 133 theme front 527:531 arg1 layer 533:537 the front layer 523:537 the front layer of E2 sequence 523:552 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 12 134 theme sequence 2297:2304 arg1 alterations 2306:2316 nucleic acid sequence alterations 2284:2316 nucleic acid sequence alterations 2284:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 9 135 from alteration 1665:1674 arg1 layer 1704:1708 the front layer 1694:1708 the front layer of soluble E2 (sE2) 1694:1728 We have identified that an alteration of amino acids in the front layer of soluble E2 (sE2) disrupts CD81 interaction and alters the cytokine response. 35612312 8 136 theme immune 1621:1626 arg1 response 1628:1635 protective immune response 1610:1635 protective immune response 1610:1635 IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. 35612312 2 137 gly glycoprotein 335:346 arg1 glycoprotein 335:346 the E2 envelope glycoprotein 319:346 the E2 envelope glycoprotein 319:346 CD81 on the cell surface facilitates HCV entry by interacting with the E2 envelope glycoprotein. 35612312 0 138 theme C 38:38 arg1 Virus 40:44 Hepatitis C Virus 28:44 Hepatitis C Virus 28:44 Modified E2 Glycoprotein of Hepatitis C Virus Enhances Proinflammatory Cytokines and Protective Immune Response. 35612312 6 139 with infection 1289:1297 arg1 model 1387:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model 1304:1391 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 6 140 theme mRNA-lipid 1040:1049 arg1 vaccine 1075:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine 1003:1081 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 3 141 theme immunity-related 381:396 arg1 cells 398:402 immunity-related cells 381:402 immunity-related cells 381:402 In addition, CD81/E2 binding on immunity-related cells may also influence host response outcome to HCV infection. 35612312 4 142 theme acid 502:505 arg1 substitution 507:518 site-specific amino acid substitution 482:518 site-specific amino acid substitution 482:518 Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. 35612312 10 143 theme binding 1902:1908 arg1 activity 1910:1917 CD81 binding activity 1897:1917 CD81 binding activity 1897:1917 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 12 144 theme amenable 2272:2279 arg1 platform 2263:2270 an mRNA-LNP platform 2251:2270 an mRNA-LNP platform amenable to nucleic acid sequence alterations 2251:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 3 145 theme response 428:435 arg1 outcome 437:443 host response outcome 423:443 host response outcome to HCV infection 423:460 In addition, CD81/E2 binding on immunity-related cells may also influence host response outcome to HCV infection. 35612312 5 146 theme significant 731:741 arg1 reduction 743:751 a significant reduction 729:751 a significant reduction in CD81 binding 729:767 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 12 147 theme nucleic 2284:2290 arg1 alterations 2306:2316 nucleic acid sequence alterations 2284:2316 nucleic acid sequence alterations 2284:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 6 148 from increase 1140:1147 arg1 antibodies 1165:1174 neutralizing antibodies 1152:1174 neutralizing antibodies against HCV pseudotype virus 1152:1203 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 5 149 link monocyte-derived 870:885 arg1 macrophages 887:897 primary monocyte-derived macrophages 862:897 primary monocyte-derived macrophages as antigen-presenting cells 862:925 The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. 35612312 10 150 theme candidate 1929:1937 arg1 vaccine 1939:1945 modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine 1808:1945 modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine 1808:1945 Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. 35612312 6 151 from protection 1270:1279 arg1 antibodies 1165:1174 neutralizing antibodies 1152:1174 neutralizing antibodies against HCV pseudotype virus 1152:1203 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 12 152 theme engineered 2226:2235 arg1 antigen 2240:2246 engineered E2 antigen 2226:2246 engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations 2226:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 9 153 theme acids 1685:1689 arg1 alteration 1665:1674 an alteration 1662:1674 an alteration of amino acids in the front layer of soluble E2 (sE2) 1662:1728 We have identified that an alteration of amino acids in the front layer of soluble E2 (sE2) disrupts CD81 interaction and alters the cytokine response. 35612312 6 154 theme isotype 1118:1124 arg1 switching 1126:1134 improved IgG1-to-IgG2a isotype switching 1095:1134 improved IgG1-to-IgG2a isotype switching 1095:1134 Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. 35612312 12 155 theme mRNA-LNP 2254:2261 arg1 platform 2263:2270 an mRNA-LNP platform 2251:2270 an mRNA-LNP platform amenable to nucleic acid sequence alterations 2251:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 2 156 theme envelope 326:333 arg1 glycoprotein 335:346 the E2 envelope glycoprotein 319:346 the E2 envelope glycoprotein 319:346 CD81 on the cell surface facilitates HCV entry by interacting with the E2 envelope glycoprotein. 35612312 12 157 from platform 2263:2270 arg1 Selection 2213:2221 Selection 2213:2221 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations 2213:2316 Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development. 35612312 1 158 theme innate 214:219 arg1 responses 241:249 innate and adaptive immune responses 214:249 innate and adaptive immune responses 214:249 Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. 34731616 5 0 theme Cryo-electron 564:576 arg1 cryo-EM 590:596 cryo-EM 590:596 cryo-EM 590:596 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 0 theme Cryo-electron 564:576 arg1 microscopy 578:587 Cryo-electron microscopy 564:587 Cryo-electron microscopy (cryo-EM) structures of these two antibodies 564:632 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 1 1 link N-linked 109:116 arg1 glycan 118:123 N-linked glycan 109:123 N-linked glycan 109:123 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 7 2 theme CD4bs 1018:1022 arg1 VRC01 1044:1048 VRC01 1044:1048 VRC01 1044:1048 By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. 34731616 7 2 theme CD4bs 1018:1022 arg1 antibodies 1024:1033 glycan276-independent CD4bs antibodies 996:1033 glycan276-independent CD4bs antibodies 996:1033 By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. 34731616 1 3 theme formidable 234:243 arg1 Recognition 94:104 Recognition 94:104 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer 94:227 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 1 3 theme formidable 234:243 arg1 challenge 245:253 a formidable challenge 232:253 a formidable challenge for many CD4bs-directed antibodies 232:288 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 6 4 theme antibodies 971:980 arg1 absence 942:948 the absence 938:948 the absence of glycan276-binding antibodies 938:980 Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. 34731616 1 5 from periphery 160:168 arg1 trimer 222:227 the HIV-envelope trimer 205:227 the HIV-envelope trimer 205:227 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 1 5 from periphery 160:168 arg1 residue 128:134 residue N276 128:139 residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer 128:227 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 1 5 from periphery 160:168 arg1 glycan276 142:150 glycan276 142:150 glycan276 142:150 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 5 6 theme HIV-envelope 723:734 arg1 trimer 736:741 HIV-envelope trimer 723:741 HIV-envelope trimer 723:741 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 7 7 theme glycan276-independent 996:1016 arg1 VRC01 1044:1048 VRC01 1044:1048 VRC01 1044:1048 By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. 34731616 7 7 theme glycan276-independent 996:1016 arg1 antibodies 1024:1033 glycan276-independent CD4bs antibodies 996:1033 glycan276-independent CD4bs antibodies 996:1033 By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. 34731616 2 8 theme glycan276-dependent 372:390 arg1 antibodies 398:407 glycan276-dependent CD4bs antibodies 372:407 glycan276-dependent CD4bs antibodies 372:407 To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. 34731616 6 9 theme glycan276-binding 953:969 arg1 antibodies 971:980 glycan276-binding antibodies 953:980 glycan276-binding antibodies 953:980 Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. 34731616 8 10 theme glycan276 1161:1169 arg1 recognition 1146:1156 antibody recognition 1137:1156 antibody recognition of glycan276 1137:1169 These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition. 34731616 1 11 theme CD4-binding 177:187 arg1 CD4bs 195:199 CD4bs 195:199 CD4bs 195:199 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 1 11 theme CD4-binding 177:187 arg1 site 189:192 the CD4-binding site 173:192 the CD4-binding site (CD4bs) on the HIV-envelope trimer 173:227 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 0 12 theme Structural 0:9 arg1 basis 11:15 Structural basis 0:15 Structural basis of glycan276-dependent recognition by HIV-1 0:59 Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies. 34731616 1 13 theme many 259:262 arg1 antibodies 279:288 many CD4bs-directed antibodies 259:288 many CD4bs-directed antibodies 259:288 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 5 14 theme antibodies 623:632 arg1 179NC75 638:644 179NC75 638:644 179NC75 638:644 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 14 theme antibodies 623:632 arg1 antibody 697:704 a previously identified glycan276-dependent CD4bs antibody 647:704 a previously identified glycan276-dependent CD4bs antibody 647:704 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 14 theme antibodies 623:632 arg1 structures 599:608 Cryo-electron microscopy (cryo-EM) structures 564:608 Cryo-electron microscopy (cryo-EM) structures of these two antibodies 564:632 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 1 15 from residue 128:134 arg1 Recognition 94:104 Recognition 94:104 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer 94:227 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 1 15 from residue 128:134 arg1 challenge 245:253 a formidable challenge 232:253 a formidable challenge for many CD4bs-directed antibodies 232:288 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 1 16 theme N-linked 109:116 arg1 glycan 118:123 N-linked glycan 109:123 N-linked glycan 109:123 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 6 17 located observed 926:933 arg1 absence 942:948 the absence 938:948 the absence of glycan276-binding antibodies 938:980 Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. 34731616 6 17 located observed 926:933 arg2 that 921:924 that 921:924 that 921:924 Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. 34731616 1 18 theme site 189:192 arg1 periphery 160:168 the periphery 156:168 the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer 156:227 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 0 19 theme glycan276-dependent 20:38 arg1 recognition 40:50 glycan276-dependent recognition 20:50 glycan276-dependent recognition 20:50 Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies. 34731616 1 20 theme CD4bs-directed 264:277 arg1 antibodies 279:288 many CD4bs-directed antibodies 259:288 many CD4bs-directed antibodies 259:288 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 8 21 theme antibody 1137:1144 arg1 recognition 1146:1156 antibody recognition 1137:1156 antibody recognition of glycan276 1137:1169 These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition. 34731616 5 22 theme microscopy 578:587 arg1 structures 599:608 Cryo-electron microscopy (cryo-EM) structures 564:608 Cryo-electron microscopy (cryo-EM) structures of these two antibodies 564:632 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 1 23 theme glycan 118:123 arg1 Recognition 94:104 Recognition 94:104 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer 94:227 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 1 23 theme glycan 118:123 arg1 challenge 245:253 a formidable challenge 232:253 a formidable challenge for many CD4bs-directed antibodies 232:288 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 8 24 theme broad 1254:1258 arg1 recognition 1266:1276 broad CD4bs recognition 1254:1276 broad CD4bs recognition 1254:1276 These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition. 34731616 6 25 theme similar 910:916 arg1 conformation 897:908 a glycan276 conformation 885:908 a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies 885:980 Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. 34731616 5 26 with complex 710:716 arg1 trimer 736:741 HIV-envelope trimer 723:741 HIV-envelope trimer 723:741 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 27 theme glycan276 783:791 arg1 recognition 793:803 glycan276 recognition 783:803 glycan276 recognition 783:803 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 2 28 theme antibodies 398:407 arg1 lineages 360:367 two lineages 356:367 two lineages of glycan276-dependent CD4bs antibodies 356:407 To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. 34731616 0 29 theme recognition 40:50 arg1 basis 11:15 Structural basis 0:15 Structural basis of glycan276-dependent recognition by HIV-1 0:59 Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies. 34731616 4 30 theme strains 508:514 arg1 panel 487:491 a panel 485:491 a panel of 208 diverse strains 485:514 clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. 34731616 3 31 theme Antibody 410:417 arg1 CH540-VRC40.01 419:432 Antibody CH540-VRC40.01 410:432 Antibody CH540-VRC40.01 ( 410:434 Antibody CH540-VRC40.01 (named for donor-lineage. 34731616 6 32 theme glycan276 887:895 arg1 conformation 897:908 a glycan276 conformation 885:908 a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies 885:980 Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. 34731616 8 33 theme CD4bs 1260:1264 arg1 recognition 1266:1276 broad CD4bs recognition 1254:1276 broad CD4bs recognition 1254:1276 These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition. 34731616 2 34 theme CD4bs 392:396 arg1 antibodies 398:407 glycan276-dependent CD4bs antibodies 372:407 glycan276-dependent CD4bs antibodies 372:407 To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. 34731616 4 35 theme diverse 500:506 arg1 strains 508:514 208 diverse strains 496:514 208 diverse strains 496:514 clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. 34731616 1 36 from trimer 222:227 arg1 periphery 160:168 the periphery 156:168 the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer 156:227 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 4 37 theme antibody 523:530 arg1 CH314-VRC33.01 532:545 antibody CH314-VRC33.01 523:545 antibody CH314-VRC33.01 523:545 clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. 34731616 5 38 theme identified 660:669 arg1 179NC75 638:644 179NC75 638:644 179NC75 638:644 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 38 theme identified 660:669 arg1 antibody 697:704 a previously identified glycan276-dependent CD4bs antibody 647:704 a previously identified glycan276-dependent CD4bs antibody 647:704 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 39 from 179NC75 638:644 arg1 complex 710:716 complex 710:716 complex with HIV-envelope trimer 710:741 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 40 theme glycan276-dependent 671:689 arg1 179NC75 638:644 179NC75 638:644 179NC75 638:644 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 40 theme glycan276-dependent 671:689 arg1 antibody 697:704 a previously identified glycan276-dependent CD4bs antibody 647:704 a previously identified glycan276-dependent CD4bs antibody 647:704 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 6 41 theme antibodies 864:873 arg1 binding 833:839 binding 833:839 binding of glycan276-dependent antibodies 833:873 Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. 34731616 5 42 theme different 764:772 arg1 modes 774:778 substantially different modes 750:778 substantially different modes of glycan276 recognition 750:803 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 43 theme CD4bs 691:695 arg1 179NC75 638:644 179NC75 638:644 179NC75 638:644 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 43 theme CD4bs 691:695 arg1 antibody 697:704 a previously identified glycan276-dependent CD4bs antibody 647:704 a previously identified glycan276-dependent CD4bs antibody 647:704 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 6 44 theme glycan276-dependent 844:862 arg1 antibodies 864:873 glycan276-dependent antibodies 844:873 glycan276-dependent antibodies 844:873 Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. 34731616 1 45 theme HIV-envelope 209:220 arg1 trimer 222:227 the HIV-envelope trimer 205:227 the HIV-envelope trimer 205:227 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 1 46 from site 189:192 arg1 trimer 222:227 the HIV-envelope trimer 205:227 the HIV-envelope trimer 205:227 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. 34731616 0 47 theme neutralizing 69:80 arg1 antibodies 82:91 neutralizing antibodies 69:91 neutralizing antibodies 69:91 Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies. 34731616 4 48 theme panel 487:491 arg1 % 480:480 81% 478:480 81% of a panel of 208 diverse strains 478:514 clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. 34731616 4 48 theme panel 487:491 arg1 panel 487:491 a panel 485:491 a panel of 208 diverse strains 485:514 clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. 34731616 5 49 theme recognition 793:803 arg1 modes 774:778 substantially different modes 750:778 substantially different modes of glycan276 recognition 750:803 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 34731616 5 50 from structures 599:608 arg1 complex 710:716 complex 710:716 complex with HIV-envelope trimer 710:741 Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. 36453881 11 0 theme immune 2174:2179 arg1 responses 2181:2189 immune responses 2174:2189 immune responses 2174:2189 However, bNAbs target diverse epitopes on the HIV-1 envelope and the virus may evolve to evade immune responses. 36453881 1 1 theme reservoir 281:289 arg1 viruses 291:297 reservoir viruses 281:297 reservoir viruses 281:297 Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies must inhibit transmitted/founder and reservoir viruses. 36453881 8 2 theme bNAbs 1716:1720 arg1 potency 1705:1711 potency 1705:1711 potency 1705:1711 The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. 36453881 8 2 theme bNAbs 1716:1720 arg1 breadth 1693:1699 breadth 1693:1699 breadth 1693:1699 The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. 36453881 14 3 from use 2831:2833 arg1 setting 2843:2849 this setting 2838:2849 this setting 2838:2849 We identify the antibodies most likely to be effective for clinical use in this setting and describe mutational patterns associated with neutralization escape from these antibodies. 36453881 7 4 gly glycosylation 1543:1555 arg2 sites 1557:1561 higher potential glycosylation sites 1526:1561 higher potential glycosylation sites 1526:1561 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 4 5 theme loop 916:919 arg1 lengths 921:927 variable loop lengths 907:927 variable loop lengths (V1 to V5) 907:938 Sequences were assessed for phylogenetic relatedness, potential N- and O-linked glycosylation, and variable loop lengths (V1 to V5). 36453881 8 6 dep breadth 1693:1699 arg1 the 1689:1691 the 1689:1691 the 1689:1691 The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. 36453881 8 7 theme circulating 1730:1740 arg1 C 1756:1756 circulating HIV-1 subtype C 1730:1756 circulating HIV-1 subtype C envelopes 1730:1766 The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. 36453881 2 8 theme Establishing 300:311 arg1 sensitivity 313:323 Establishing sensitivity 300:323 Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability 300:413 Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability may guide rational bNAbs selection for clinical development. 36453881 13 9 theme C 2700:2700 arg1 individuals 2711:2721 subtype C infected individuals 2692:2721 subtype C infected individuals 2692:2721 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 7 10 theme signature 1624:1632 arg1 " 1633:1633 known "signature" 1617:1633 known "signature" mutations 1617:1643 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 8 11 theme subtype 1748:1754 arg1 C 1756:1756 circulating HIV-1 subtype C 1730:1756 circulating HIV-1 subtype C envelopes 1730:1766 The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. 36453881 7 12 theme known 1617:1621 arg1 " 1633:1633 known "signature" 1617:1633 known "signature" mutations 1617:1643 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 10 13 theme neutralizing 1974:1985 arg1 bNAbs 1999:2003 bNAbs 1999:2003 bNAbs 1999:2003 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 10 13 theme neutralizing 1974:1985 arg1 antibodies 1987:1996 IMPORTANCE Broadly neutralizing antibodies 1955:1996 IMPORTANCE Broadly neutralizing antibodies (bNAbs) 1955:2004 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 0 14 theme HIV-1 137:141 arg1 Infection 153:161 Acute HIV-1 Subtype C Infection 131:161 Acute HIV-1 Subtype C Infection 131:161 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 3 15 theme first 634:638 arg1 detection 640:648 the first detection 630:648 the first detection of plasma viremia 630:666 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 1 16 theme prevention 214:223 arg1 strategies 233:242 HIV-1 prevention or cure strategies 208:242 HIV-1 prevention or cure strategies 208:242 Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies must inhibit transmitted/founder and reservoir viruses. 36453881 3 17 theme single 492:497 arg1 genomes 503:509 326 single env genomes 488:509 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection 488:587 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 5 18 theme gp120/gp41 1193:1202 arg1 interface 1204:1212 gp120/gp41 interface 1193:1212 gp120/gp41 interface 1193:1212 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 5 19 theme neutralization 1091:1104 arg1 profiles 1106:1113 the neutralization profiles 1087:1113 the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide 1087:1232 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 1 20 theme cure 228:231 arg1 strategies 233:242 HIV-1 prevention or cure strategies 208:242 HIV-1 prevention or cure strategies 208:242 Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies must inhibit transmitted/founder and reservoir viruses. 36453881 8 21 from variability 1674:1684 arg1 potency 1705:1711 potency 1705:1711 potency 1705:1711 The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. 36453881 8 21 from variability 1674:1684 arg1 breadth 1693:1699 breadth 1693:1699 breadth 1693:1699 The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. 36453881 3 22 theme viremia 660:666 arg1 detection 640:648 the first detection 630:648 the first detection of plasma viremia 630:666 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 5 23 theme env 955:957 arg1 amplicons 959:967 43 env amplicons 952:967 43 env amplicons (median = 3 per patient per time point) 952:1007 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 13 24 gly glycoprotein 2465:2476 arg1 glycoprotein 2465:2476 the HIV-1 Env glycoprotein 2451:2476 the HIV-1 Env glycoprotein 2451:2476 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 13 25 theme Env 2461:2463 arg1 glycoprotein 2465:2476 the HIV-1 Env glycoprotein 2451:2476 the HIV-1 Env glycoprotein 2451:2476 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 3 26 theme 1,709 days 676:685 arg1 postinfection 687:699 1,709 days postinfection 676:699 1,709 days postinfection 676:699 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 9 27 dep N6.LS 1779:1783 arg1 10-1074 1801:1807 10-1074 1801:1807 10-1074 1801:1807 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 9 27 dep N6.LS 1779:1783 arg1 PGT121 1814:1819 PGT121 1814:1819 PGT121 1814:1819 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 9 27 dep N6.LS 1779:1783 arg1 PGT151 1793:1798 PGT151 1793:1798 PGT151 1793:1798 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 9 27 dep N6.LS 1779:1783 arg1 VRC01 1786:1790 VRC01 1786:1790 VRC01 1786:1790 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 1 28 theme Broadly 164:170 arg1 bNAbs 197:201 bNAbs 197:201 bNAbs 197:201 Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies must inhibit transmitted/founder and reservoir viruses. 36453881 1 28 theme Broadly 164:170 arg1 antibodies 185:194 Broadly neutralizing antibodies 164:194 Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies 164:242 Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies must inhibit transmitted/founder and reservoir viruses. 36453881 7 29 theme longer 1581:1586 arg1 mutations 1635:1643 known "signature" mutations 1617:1643 known "signature" mutations 1617:1643 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 7 29 theme longer 1581:1586 arg1 domains 1598:1604 relatively longer V1 and V4 domains 1570:1604 relatively longer V1 and V4 domains 1570:1604 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 0 30 from Alterations 20:30 arg1 Sequence 39:46 Env Sequence 35:46 Env Sequence 35:46 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 9 31 theme broad 1829:1833 arg1 activity 1835:1842 broad activity 1829:1842 broad activity against subtype C variants 1829:1869 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 5 32 theme binding 1145:1151 arg1 site 1153:1156 the CD4 binding site 1137:1156 the CD4 binding site 1137:1156 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 6 33 theme neutralization 1251:1264 arg1 breadths 1266:1273 the neutralization breadths 1247:1273 the neutralization breadths 1247:1273 At 1 μg/mL, the neutralization breadths were as follows: VRC07-LS and N6.LS (100%), VRC01 (86%), PGT151 (81%), 10-1074 and PGT121 (80%), and less than 70% for 10E8, 3BNC117, CAP256.VRC26, 4E10, PGDM1400, and N123-VRC34.01. 36453881 5 34 dep amplicons 959:967 arg1 median = 3 970:979 median = 3 970:979 median = 3 per patient per time point 970:1006 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 0 35 theme Neutralizing 97:108 arg1 Antibodies 110:119 Broadly Neutralizing Antibodies 89:119 Broadly Neutralizing Antibodies 89:119 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 7 36 theme glycosylation 1543:1555 arg1 sites 1557:1561 higher potential glycosylation sites 1526:1561 higher potential glycosylation sites 1526:1561 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 12 37 theme genetic 2305:2311 arg1 patterns 2313:2320 the genetic patterns 2301:2320 the genetic patterns that may lead to neutralization escape 2301:2359 It is therefore important to identify antibodies with broad activity in high prevalence settings, as well as the genetic patterns that may lead to neutralization escape. 36453881 9 38 theme C 1860:1860 arg1 variants 1862:1869 subtype C variants 1852:1869 subtype C variants 1852:1869 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 2 39 theme clinical 454:461 arg1 development 463:473 clinical development 454:473 clinical development 454:473 Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability may guide rational bNAbs selection for clinical development. 36453881 5 40 theme bNAbs 1121:1125 arg1 profiles 1106:1113 the neutralization profiles 1087:1113 the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide 1087:1232 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 7 41 theme higher 1526:1531 arg1 sites 1557:1561 higher potential glycosylation sites 1526:1561 higher potential glycosylation sites 1526:1561 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 13 42 theme glycoprotein 2465:2476 arg1 epitopes 2439:2446 six epitopes 2435:2446 six epitopes of the HIV-1 Env glycoprotein 2435:2476 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 0 43 theme Subtle 0:5 arg1 Alterations 20:30 Subtle Longitudinal Alterations 0:30 Subtle Longitudinal Alterations in Env Sequence 0:46 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 4 44 link O-linked 879:886 arg1 glycosylation 888:900 O-linked glycosylation 879:900 O-linked glycosylation 879:900 Sequences were assessed for phylogenetic relatedness, potential N- and O-linked glycosylation, and variable loop lengths (V1 to V5). 36453881 9 45 theme major 1876:1880 arg1 determinants 1882:1893 major determinants 1876:1893 major determinants of sensitivity to most bNAbs 1876:1922 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 14 46 theme likely 2795:2800 arg1 antibodies 2779:2788 the antibodies 2775:2788 the antibodies most likely to be effective for clinical use in this setting 2775:2849 We identify the antibodies most likely to be effective for clinical use in this setting and describe mutational patterns associated with neutralization escape from these antibodies. 36453881 13 47 theme burden 2747:2752 arg1 country 2754:2760 a high burden country 2740:2760 a high burden country 2740:2760 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 13 47 theme burden 2747:2752 arg1 ART 2685:2687 ART 2685:2687 ART in subtype C infected individuals in South Africa 2685:2737 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 12 48 theme prevalence 2269:2278 arg1 settings 2280:2287 high prevalence settings 2264:2287 high prevalence settings 2264:2287 It is therefore important to identify antibodies with broad activity in high prevalence settings, as well as the genetic patterns that may lead to neutralization escape. 36453881 3 49 theme antiretroviral 725:738 arg1 ART 749:751 ART 749:751 ART 749:751 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 3 49 theme antiretroviral 725:738 arg1 median = 724 days 755:771 median = 724 days 755:771 median = 724 days 755:771 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 3 49 theme antiretroviral 725:738 arg1 therapy 740:746 antiretroviral therapy 725:746 antiretroviral therapy (ART) (median = 724 days) 725:772 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 0 50 theme Env 35:37 arg1 Sequence 39:46 Env Sequence 35:46 Env Sequence 35:46 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 2 51 theme neutralization 388:401 arg1 variability 403:413 neutralization variability 388:413 neutralization variability 388:413 Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability may guide rational bNAbs selection for clinical development. 36453881 3 52 theme acute 567:571 arg1 infection 579:587 acute HIV-1 infection 567:587 acute HIV-1 infection 567:587 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 13 53 theme diverse 2392:2398 arg1 properties 2412:2421 diverse biophysical properties 2392:2421 diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country 2392:2760 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 5 54 theme TZM-bl 1055:1060 arg1 assay 1062:1066 the TZM-bl assay 1051:1066 the TZM-bl assay 1051:1066 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 11 55 from epitopes 2109:2116 arg1 envelope 2131:2138 the HIV-1 envelope 2121:2138 the HIV-1 envelope 2121:2138 However, bNAbs target diverse epitopes on the HIV-1 envelope and the virus may evolve to evade immune responses. 36453881 4 56 theme potential 862:870 arg1 N- 872:873 potential N- 862:873 potential N- 862:873 Sequences were assessed for phylogenetic relatedness, potential N- and O-linked glycosylation, and variable loop lengths (V1 to V5). 36453881 13 57 with bNAbs 2381:2385 arg1 properties 2412:2421 diverse biophysical properties 2392:2421 diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country 2392:2760 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 14 58 from antibodies 2933:2942 arg1 escape 2915:2920 neutralization escape 2900:2920 neutralization escape from these antibodies 2900:2942 We identify the antibodies most likely to be effective for clinical use in this setting and describe mutational patterns associated with neutralization escape from these antibodies. 36453881 2 59 theme rational 425:432 arg1 selection 440:448 rational bNAbs selection 425:448 rational bNAbs selection for clinical development 425:473 Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability may guide rational bNAbs selection for clinical development. 36453881 13 60 theme infected 2702:2709 arg1 individuals 2711:2721 subtype C infected individuals 2692:2721 subtype C infected individuals 2692:2721 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 5 61 theme expression 1029:1038 arg1 vector 1040:1045 an expression vector 1026:1045 an expression vector 1026:1045 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 9 62 theme V1/V4 1940:1944 arg1 domains 1946:1952 the V1/V4 domains 1936:1952 the V1/V4 domains 1936:1952 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 12 63 theme neutralization 2339:2352 arg1 escape 2354:2359 neutralization escape 2339:2359 neutralization escape 2339:2359 It is therefore important to identify antibodies with broad activity in high prevalence settings, as well as the genetic patterns that may lead to neutralization escape. 36453881 2 64 theme circulating 328:338 arg1 viruses 340:346 circulating viruses 328:346 circulating viruses 328:346 Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability may guide rational bNAbs selection for clinical development. 36453881 10 65 theme potential 2011:2019 arg1 utility 2030:2036 potential clinical utility 2011:2036 potential clinical utility 2011:2036 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 7 66 theme " 1633:1633 arg1 mutations 1635:1643 known "signature" mutations 1617:1643 known "signature" mutations 1617:1643 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 11 67 theme diverse 2101:2107 arg1 epitopes 2109:2116 diverse epitopes 2101:2116 diverse epitopes on the HIV-1 envelope 2101:2138 However, bNAbs target diverse epitopes on the HIV-1 envelope and the virus may evolve to evade immune responses. 36453881 3 68 theme ART 792:794 arg1 initiation 796:805 ART initiation 792:805 ART initiation 792:805 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 8 69 theme HIV-1 1742:1746 arg1 C 1756:1756 circulating HIV-1 subtype C 1730:1756 circulating HIV-1 subtype C envelopes 1730:1766 The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. 36453881 6 70 dep were 1275:1278 arg1 % 1315:1315 100% 1312:1315 100% 1312:1315 At 1 μg/mL, the neutralization breadths were as follows: VRC07-LS and N6.LS (100%), VRC01 (86%), PGT151 (81%), 10-1074 and PGT121 (80%), and less than 70% for 10E8, 3BNC117, CAP256.VRC26, 4E10, PGDM1400, and N123-VRC34.01. 36453881 6 70 dep were 1275:1278 arg1 % 1328:1328 86% 1326:1328 86% 1326:1328 At 1 μg/mL, the neutralization breadths were as follows: VRC07-LS and N6.LS (100%), VRC01 (86%), PGT151 (81%), 10-1074 and PGT121 (80%), and less than 70% for 10E8, 3BNC117, CAP256.VRC26, 4E10, PGDM1400, and N123-VRC34.01. 36453881 6 70 dep were 1275:1278 arg1 N123-VRC34.01 1443:1455 N123-VRC34.01 1443:1455 N123-VRC34.01 1443:1455 At 1 μg/mL, the neutralization breadths were as follows: VRC07-LS and N6.LS (100%), VRC01 (86%), PGT151 (81%), 10-1074 and PGT121 (80%), and less than 70% for 10E8, 3BNC117, CAP256.VRC26, 4E10, PGDM1400, and N123-VRC34.01. 36453881 6 70 dep were 1275:1278 arg1 VRC07-LS 1292:1299 VRC07-LS 1292:1299 VRC07-LS 1292:1299 At 1 μg/mL, the neutralization breadths were as follows: VRC07-LS and N6.LS (100%), VRC01 (86%), PGT151 (81%), 10-1074 and PGT121 (80%), and less than 70% for 10E8, 3BNC117, CAP256.VRC26, 4E10, PGDM1400, and N123-VRC34.01. 36453881 6 70 dep were 1275:1278 arg1 VRC01 1319:1323 VRC01 1319:1323 VRC01 1319:1323 At 1 μg/mL, the neutralization breadths were as follows: VRC07-LS and N6.LS (100%), VRC01 (86%), PGT151 (81%), 10-1074 and PGT121 (80%), and less than 70% for 10E8, 3BNC117, CAP256.VRC26, 4E10, PGDM1400, and N123-VRC34.01. 36453881 6 70 dep were 1275:1278 arg1 N6.LS 1305:1309 N6.LS 1305:1309 N6.LS 1305:1309 At 1 μg/mL, the neutralization breadths were as follows: VRC07-LS and N6.LS (100%), VRC01 (86%), PGT151 (81%), 10-1074 and PGT121 (80%), and less than 70% for 10E8, 3BNC117, CAP256.VRC26, 4E10, PGDM1400, and N123-VRC34.01. 36453881 13 71 theme subtype 2692:2698 arg1 C 2700:2700 subtype C 2692:2700 subtype C infected individuals 2692:2721 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 4 72 theme variable 907:914 arg1 lengths 921:927 variable loop lengths 907:927 variable loop lengths (V1 to V5) 907:938 Sequences were assessed for phylogenetic relatedness, potential N- and O-linked glycosylation, and variable loop lengths (V1 to V5). 36453881 8 73 theme C 1756:1756 arg1 envelopes 1758:1766 circulating HIV-1 subtype C envelopes 1730:1766 circulating HIV-1 subtype C envelopes 1730:1766 The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. 36453881 14 74 theme neutralization 2900:2913 arg1 escape 2915:2920 neutralization escape 2900:2920 neutralization escape from these antibodies 2900:2942 We identify the antibodies most likely to be effective for clinical use in this setting and describe mutational patterns associated with neutralization escape from these antibodies. 36453881 11 75 theme HIV-1 2125:2129 arg1 envelope 2131:2138 the HIV-1 envelope 2121:2138 the HIV-1 envelope 2121:2138 However, bNAbs target diverse epitopes on the HIV-1 envelope and the virus may evolve to evade immune responses. 36453881 5 76 used used 1072:1075 arg2 assay 1062:1066 the TZM-bl assay 1051:1066 the TZM-bl assay 1051:1066 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 0 77 theme Subtype 143:149 arg1 Infection 153:161 Acute HIV-1 Subtype C Infection 131:161 Acute HIV-1 Subtype C Infection 131:161 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 1 78 theme HIV-1 208:212 arg1 prevention 214:223 HIV-1 prevention 208:223 HIV-1 prevention 208:223 Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies must inhibit transmitted/founder and reservoir viruses. 36453881 7 79 theme low 1483:1485 arg1 sensitivity 1487:1497 low sensitivity 1483:1497 low sensitivity to V1/V2 and V3 bNAbs 1483:1519 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 10 80 theme Broadly 1966:1972 arg1 bNAbs 1999:2003 bNAbs 1999:2003 bNAbs 1999:2003 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 10 80 theme Broadly 1966:1972 arg1 antibodies 1987:1996 IMPORTANCE Broadly neutralizing antibodies 1955:1996 IMPORTANCE Broadly neutralizing antibodies (bNAbs) 1955:2004 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 10 81 contain have 2006:2009 arg2 utility 2030:2036 potential clinical utility 2011:2036 potential clinical utility 2011:2036 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 10 81 contain have 2006:2009 arg1 bNAbs 1999:2003 bNAbs 1999:2003 bNAbs 1999:2003 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 10 81 contain have 2006:2009 arg1 antibodies 1987:1996 IMPORTANCE Broadly neutralizing antibodies 1955:1996 IMPORTANCE Broadly neutralizing antibodies (bNAbs) 1955:2004 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 14 82 theme mutational 2864:2873 arg1 patterns 2875:2882 mutational patterns 2864:2882 mutational patterns associated with neutralization escape from these antibodies 2864:2942 We identify the antibodies most likely to be effective for clinical use in this setting and describe mutational patterns associated with neutralization escape from these antibodies. 36453881 12 83 with patterns 2313:2320 arg1 activity 2252:2259 broad activity 2246:2259 broad activity in high prevalence settings 2246:2287 It is therefore important to identify antibodies with broad activity in high prevalence settings, as well as the genetic patterns that may lead to neutralization escape. 36453881 12 84 theme broad 2246:2250 arg1 activity 2252:2259 broad activity 2246:2259 broad activity in high prevalence settings 2246:2287 It is therefore important to identify antibodies with broad activity in high prevalence settings, as well as the genetic patterns that may lead to neutralization escape. 36453881 12 85 from activity 2252:2259 arg1 settings 2280:2287 high prevalence settings 2264:2287 high prevalence settings 2264:2287 It is therefore important to identify antibodies with broad activity in high prevalence settings, as well as the genetic patterns that may lead to neutralization escape. 36453881 3 86 theme plasma 653:658 arg1 viremia 660:666 plasma viremia 653:666 plasma viremia 653:666 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 5 87 theme amplicons 959:967 arg1 total 943:947 A total 941:947 A total of 43 env amplicons (median = 3 per patient per time point) 941:1007 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 13 88 theme HIV-1 2455:2459 arg1 glycoprotein 2465:2476 the HIV-1 Env glycoprotein 2451:2476 the HIV-1 Env glycoprotein 2451:2476 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 7 89 theme V4 1595:1596 arg1 mutations 1635:1643 known "signature" mutations 1617:1643 known "signature" mutations 1617:1643 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 7 89 theme V4 1595:1596 arg1 domains 1598:1604 relatively longer V1 and V4 domains 1570:1604 relatively longer V1 and V4 domains 1570:1604 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 10 90 theme clinical 2021:2028 arg1 utility 2030:2036 potential clinical utility 2011:2036 potential clinical utility 2011:2036 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 0 91 theme Broadly 89:95 arg1 Antibodies 110:119 Broadly Neutralizing Antibodies 89:119 Broadly Neutralizing Antibodies 89:119 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 5 92 theme CD4 1141:1143 arg1 site 1153:1156 the CD4 binding site 1137:1156 the CD4 binding site 1137:1156 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 1 93 theme neutralizing 172:183 arg1 bNAbs 197:201 bNAbs 197:201 bNAbs 197:201 Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies must inhibit transmitted/founder and reservoir viruses. 36453881 1 93 theme neutralizing 172:183 arg1 antibodies 185:194 Broadly neutralizing antibodies 164:194 Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies 164:242 Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies must inhibit transmitted/founder and reservoir viruses. 36453881 7 94 theme V1 1588:1589 arg1 mutations 1635:1643 known "signature" mutations 1617:1643 known "signature" mutations 1617:1643 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 7 94 theme V1 1588:1589 arg1 domains 1598:1604 relatively longer V1 and V4 domains 1570:1604 relatively longer V1 and V4 domains 1570:1604 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 10 95 theme cure 2062:2065 arg1 strategies 2067:2076 HIV-1 prevention and cure strategies 2041:2076 HIV-1 prevention and cure strategies 2041:2076 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 7 96 dep V1/V2 1502:1506 arg1 bNAbs 1515:1519 bNAbs 1515:1519 bNAbs 1515:1519 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 10 97 theme prevention 2047:2056 arg1 strategies 2067:2076 HIV-1 prevention and cure strategies 2041:2076 HIV-1 prevention and cure strategies 2041:2076 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 5 98 theme time 997:1000 arg1 point 1002:1006 time point 997:1006 time point 997:1006 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 2 99 theme viruses 340:346 arg1 sensitivity 313:323 Establishing sensitivity 300:323 Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability 300:413 Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability may guide rational bNAbs selection for clinical development. 36453881 0 100 from Differences 59:69 arg1 Sensitivity 74:84 Sensitivity 74:84 Sensitivity to Broadly Neutralizing Antibodies 74:119 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 9 101 theme subtype 1852:1858 arg1 variants 1862:1869 subtype C variants 1852:1869 subtype C variants 1852:1869 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 0 102 theme Acute 131:135 arg1 Infection 153:161 Acute HIV-1 Subtype C Infection 131:161 Acute HIV-1 Subtype C Infection 131:161 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 8 103 theme significant 1662:1672 arg1 variability 1674:1684 significant variability 1662:1684 significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes 1662:1766 The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. 36453881 4 104 theme phylogenetic 836:847 arg1 relatedness 849:859 phylogenetic relatedness 836:859 phylogenetic relatedness 836:859 Sequences were assessed for phylogenetic relatedness, potential N- and O-linked glycosylation, and variable loop lengths (V1 to V5). 36453881 14 105 theme clinical 2822:2829 arg1 use 2831:2833 clinical use 2822:2833 clinical use in this setting 2822:2849 We identify the antibodies most likely to be effective for clinical use in this setting and describe mutational patterns associated with neutralization escape from these antibodies. 36453881 0 106 theme Longitudinal 7:18 arg1 Alterations 20:30 Subtle Longitudinal Alterations 0:30 Subtle Longitudinal Alterations in Env Sequence 0:46 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 13 107 theme antiretroviral 2599:2612 arg1 treatment 2614:2622 antiretroviral treatment 2599:2622 antiretroviral treatment (ART) 2599:2628 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 13 107 theme antiretroviral 2599:2612 arg1 ART 2625:2627 ART 2625:2627 ART 2625:2627 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 7 108 theme potential 1533:1541 arg1 sites 1557:1561 higher potential glycosylation sites 1526:1561 higher potential glycosylation sites 1526:1561 Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. 36453881 12 109 theme high 2264:2267 arg1 settings 2280:2287 high prevalence settings 2264:2287 high prevalence settings 2264:2287 It is therefore important to identify antibodies with broad activity in high prevalence settings, as well as the genetic patterns that may lead to neutralization escape. 36453881 12 110 with antibodies 2230:2239 arg1 activity 2252:2259 broad activity 2246:2259 broad activity in high prevalence settings 2246:2287 It is therefore important to identify antibodies with broad activity in high prevalence settings, as well as the genetic patterns that may lead to neutralization escape. 36453881 2 111 theme bNAbs 434:438 arg1 selection 440:448 rational bNAbs selection 425:448 rational bNAbs selection for clinical development 425:473 Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability may guide rational bNAbs selection for clinical development. 36453881 13 112 from ART 2685:2687 arg1 individuals 2711:2721 subtype C infected individuals 2692:2721 subtype C infected individuals 2692:2721 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 13 112 from ART 2685:2687 arg1 Africa 2732:2737 Africa 2732:2737 Africa 2732:2737 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 10 113 theme HIV-1 2041:2045 arg1 prevention 2047:2056 HIV-1 prevention 2041:2056 HIV-1 prevention 2041:2056 IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. 36453881 3 114 theme env 499:501 arg1 genomes 503:509 326 single env genomes 488:509 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection 488:587 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 9 115 theme sensitivity 1898:1908 arg1 determinants 1882:1893 major determinants 1876:1893 major determinants of sensitivity to most bNAbs 1876:1922 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 4 116 theme O-linked 879:886 arg1 glycosylation 888:900 O-linked glycosylation 879:900 O-linked glycosylation 879:900 Sequences were assessed for phylogenetic relatedness, potential N- and O-linked glycosylation, and variable loop lengths (V1 to V5). 36453881 5 117 theme V1/V2 1159:1163 arg1 region 1165:1170 V1/V2 region 1159:1170 V1/V2 region 1159:1170 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 0 118 theme C 151:151 arg1 Infection 153:161 Acute HIV-1 Subtype C Infection 131:161 Acute HIV-1 Subtype C Infection 131:161 Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. 36453881 9 119 theme most 1913:1916 arg1 bNAbs 1918:1922 most bNAbs 1913:1922 most bNAbs 1913:1922 VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. 36453881 3 120 from individuals 521:531 arg1 genomes 503:509 326 single env genomes 488:509 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection 488:587 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 3 121 theme HIV-1 573:577 arg1 infection 579:587 acute HIV-1 infection 567:587 acute HIV-1 infection 567:587 We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. 36453881 2 122 theme genetic 361:367 arg1 patterns 369:376 genetic patterns 361:376 genetic patterns 361:376 Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability may guide rational bNAbs selection for clinical development. 36453881 13 123 theme chronic 2574:2580 arg1 infection 2582:2590 chronic infection 2574:2590 chronic infection before antiretroviral treatment (ART) 2574:2628 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 5 124 theme fusion 1219:1224 arg1 peptide 1226:1232 fusion peptide 1219:1232 fusion peptide 1219:1232 A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. 36453881 13 125 theme high 2742:2745 arg1 country 2754:2760 a high burden country 2740:2760 a high burden country 2740:2760 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 13 125 theme high 2742:2745 arg1 ART 2685:2687 ART 2685:2687 ART in subtype C infected individuals in South Africa 2685:2737 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 36453881 4 126 dep lengths 921:927 arg1 V1 930:931 V1 930:931 V1 930:931 Sequences were assessed for phylogenetic relatedness, potential N- and O-linked glycosylation, and variable loop lengths (V1 to V5). 36453881 13 127 theme biophysical 2400:2410 arg1 properties 2412:2421 diverse biophysical properties 2392:2421 diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country 2392:2760 We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. 35879285 11 0 theme pathologic 1744:1753 arg1 resorption 1760:1769 pathologic bone resorption 1744:1769 pathologic bone resorption 1744:1769 These findings highlight an important role of O-GlcNAcylation in osteoclastogenesis and may offer the potential to therapeutically interfere with pathologic bone resorption. 35879285 9 1 theme experimental 1455:1466 arg1 arthritis 1468:1476 experimental arthritis 1455:1476 experimental arthritis 1455:1476 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 8 2 theme O-GlcNAcylation 1139:1153 arg1 regulation 1125:1134 the dynamic regulation 1113:1134 the dynamic regulation of O-GlcNAcylation 1113:1153 TNFα fosters the dynamic regulation of O-GlcNAcylation to promote osteoclastogenesis in inflammatory arthritis. 35879285 1 3 theme osteoclast-induced 153:170 arg1 resorption 177:186 osteoclast-induced bone resorption 153:186 osteoclast-induced bone resorption 153:186 Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered bone formation. 35879285 9 4 theme Targeted 1212:1219 arg1 inhibition 1247:1256 Targeted pharmaceutical or genetic inhibition 1212:1256 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) 1212:1307 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 4 5 theme common 631:636 arg1 modifications 646:658 the most common protein modifications 622:658 the most common protein modifications 622:658 Although O-GlcNAcylation is one of the most common protein modifications, its role in bone homeostasis has not been systematically investigated. 35879285 0 6 from changes 8:14 arg1 O-GlcNAcylation 19:33 O-GlcNAcylation 19:33 O-GlcNAcylation 19:33 Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153. 35879285 11 7 theme bone 1755:1758 arg1 resorption 1760:1769 pathologic bone resorption 1744:1769 pathologic bone resorption 1744:1769 These findings highlight an important role of O-GlcNAcylation in osteoclastogenesis and may offer the potential to therapeutically interfere with pathologic bone resorption. 35879285 1 8 theme bone 172:175 arg1 resorption 177:186 osteoclast-induced bone resorption 153:186 osteoclast-induced bone resorption 153:186 Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered bone formation. 35879285 9 9 theme pharmaceutical 1221:1234 arg1 inhibition 1247:1256 Targeted pharmaceutical or genetic inhibition 1212:1256 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) 1212:1307 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 10 10 theme OGT 1550:1552 arg1 inhibition 1554:1563 OGT inhibition 1550:1563 OGT inhibition 1550:1563 Knockdown of NUP153, an O-GlcNAcylation target, has similar effects as OGT inhibition and inhibits osteoclastogenesis. 35879285 9 11 theme early 1351:1355 arg1 stages 1357:1362 early stages 1351:1362 early stages of differentiation 1351:1381 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 2 12 theme increased 299:307 arg1 differentiation 320:334 increased osteoclast differentiation 299:334 increased osteoclast differentiation 299:334 In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. 35879285 6 13 dep promotes 850:857 arg1 whereas 911:917 whereas 911:917 whereas 911:917 Increased O-GlcNAcylation promotes osteoclast differentiation during the early stages, whereas its downregulation is required for osteoclast maturation. 35879285 4 14 theme modifications 646:658 arg1 one 615:617 one 615:617 one 615:617 Although O-GlcNAcylation is one of the most common protein modifications, its role in bone homeostasis has not been systematically investigated. 35879285 4 14 theme modifications 646:658 arg1 modifications 646:658 the most common protein modifications 622:658 the most common protein modifications 622:658 Although O-GlcNAcylation is one of the most common protein modifications, its role in bone homeostasis has not been systematically investigated. 35879285 3 15 with modification 442:453 arg1 attachment 460:469 attachment 460:469 attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins 460:584 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 7 16 theme cell-cell 1082:1090 arg1 fusion 1092:1097 cell-cell fusion 1082:1097 cell-cell fusion 1082:1097 At the molecular level, O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell fusion. 35879285 2 17 theme progressive 380:390 arg1 loss 397:400 progressive bone loss 380:400 progressive bone loss 380:400 In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. 35879285 9 18 theme genetic 1239:1245 arg1 inhibition 1247:1256 Targeted pharmaceutical or genetic inhibition 1212:1256 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) 1212:1307 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 4 19 theme protein 638:644 arg1 modifications 646:658 the most common protein modifications 622:658 the most common protein modifications 622:658 Although O-GlcNAcylation is one of the most common protein modifications, its role in bone homeostasis has not been systematically investigated. 35879285 11 20 theme important 1626:1634 arg1 role 1636:1639 an important role 1623:1639 an important role of O-GlcNAcylation in osteoclastogenesis 1623:1680 These findings highlight an important role of O-GlcNAcylation in osteoclastogenesis and may offer the potential to therapeutically interfere with pathologic bone resorption. 35879285 8 21 theme dynamic 1117:1123 arg1 regulation 1125:1134 the dynamic regulation 1113:1134 the dynamic regulation of O-GlcNAcylation 1113:1153 TNFα fosters the dynamic regulation of O-GlcNAcylation to promote osteoclastogenesis in inflammatory arthritis. 35879285 3 22 theme proteins 577:584 arg1 serine 538:543 serine 538:543 serine 538:543 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 3 22 theme proteins 577:584 arg1 threonine 548:556 threonine 548:556 threonine 548:556 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 3 23 theme single 476:481 arg1 residue 527:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 6 24 theme osteoclast 954:963 arg1 maturation 965:974 osteoclast maturation 954:974 osteoclast maturation 954:974 Increased O-GlcNAcylation promotes osteoclast differentiation during the early stages, whereas its downregulation is required for osteoclast maturation. 35879285 11 25 from role 1636:1639 arg1 osteoclastogenesis 1663:1680 osteoclastogenesis 1663:1680 osteoclastogenesis 1663:1680 These findings highlight an important role of O-GlcNAcylation in osteoclastogenesis and may offer the potential to therapeutically interfere with pathologic bone resorption. 35879285 3 26 theme O-linked 483:490 arg1 residue 527:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 9 27 theme differentiation 1367:1381 arg1 stages 1357:1362 early stages 1351:1362 early stages of differentiation 1351:1381 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 8 28 theme inflammatory 1188:1199 arg1 arthritis 1201:1209 inflammatory arthritis 1188:1209 inflammatory arthritis 1188:1209 TNFα fosters the dynamic regulation of O-GlcNAcylation to promote osteoclastogenesis in inflammatory arthritis. 35879285 9 29 theme O-GlcNAc 1261:1268 arg1 OGT 1283:1285 OGT 1283:1285 OGT 1283:1285 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 9 29 theme O-GlcNAc 1261:1268 arg1 transferase 1270:1280 O-GlcNAc transferase 1261:1280 O-GlcNAc transferase (OGT) 1261:1286 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 1 30 theme osteoblast-triggered 192:211 arg1 formation 218:226 osteoblast-triggered bone formation 192:226 osteoblast-triggered bone formation 192:226 Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered bone formation. 35879285 0 31 theme Dynamic 0:6 arg1 changes 8:14 Dynamic changes 0:14 Dynamic changes in O-GlcNAcylation 0:33 Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153. 35879285 3 32 link O-linked 483:490 arg1 residue 527:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 9 33 theme transferase 1270:1280 arg1 inhibition 1247:1256 Targeted pharmaceutical or genetic inhibition 1212:1256 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) 1212:1307 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 1 34 theme bone 213:216 arg1 formation 218:226 osteoblast-triggered bone formation 192:226 osteoblast-triggered bone formation 192:226 Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered bone formation. 35879285 7 35 theme oxidative 1052:1060 arg1 phosphorylation 1062:1076 oxidative phosphorylation 1052:1076 oxidative phosphorylation 1052:1076 At the molecular level, O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell fusion. 35879285 1 36 theme Bone 106:109 arg1 mass 111:114 Bone mass 106:114 Bone mass 106:114 Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered bone formation. 35879285 10 37 theme NUP153 1492:1497 arg1 Knockdown 1479:1487 Knockdown 1479:1487 Knockdown of NUP153, an O-GlcNAcylation target, 1479:1525 Knockdown of NUP153, an O-GlcNAcylation target, has similar effects as OGT inhibition and inhibits osteoclastogenesis. 35879285 2 38 dep such 255:258 arg1 as 260:261 as 260:261 as 260:261 In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. 35879285 3 39 dep serine 538:543 arg1 residues 558:565 residues 558:565 residues 558:565 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 3 40 attach attachment 460:469 arg1 serine 538:543 serine 538:543 serine 538:543 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 3 40 attach attachment 460:469 arg2 residue 527:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 3 40 attach attachment 460:469 arg1 threonine 548:556 threonine 548:556 threonine 548:556 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 2 41 theme osteoclast 309:318 arg1 differentiation 320:334 increased osteoclast differentiation 299:334 increased osteoclast differentiation 299:334 In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. 35879285 4 42 theme bone 673:676 arg1 homeostasis 678:688 bone homeostasis 673:688 bone homeostasis 673:688 Although O-GlcNAcylation is one of the most common protein modifications, its role in bone homeostasis has not been systematically investigated. 35879285 0 43 theme osteoclast 44:53 arg1 differentiation 55:69 osteoclast differentiation 44:69 osteoclast differentiation 44:69 Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153. 35879285 2 44 theme rheumatoid 263:272 arg1 RA 285:286 RA 285:286 RA 285:286 In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. 35879285 2 44 theme rheumatoid 263:272 arg1 arthritis 274:282 rheumatoid arthritis 263:282 inflammatory arthritis such as rheumatoid arthritis (RA) 232:287 In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. 35879285 11 45 theme O-GlcNAcylation 1644:1658 arg1 role 1636:1639 an important role 1623:1639 an important role of O-GlcNAcylation in osteoclastogenesis 1623:1680 These findings highlight an important role of O-GlcNAcylation in osteoclastogenesis and may offer the potential to therapeutically interfere with pathologic bone resorption. 35879285 3 46 theme β-D-N-acetylglucosamine 492:514 arg1 residue 527:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 10 47 contain has 1527:1529 arg2 effects 1539:1545 similar effects 1531:1545 similar effects 1531:1545 Knockdown of NUP153, an O-GlcNAcylation target, has similar effects as OGT inhibition and inhibits osteoclastogenesis. 35879285 10 47 contain has 1527:1529 arg1 Knockdown 1479:1487 Knockdown 1479:1487 Knockdown of NUP153, an O-GlcNAcylation target, 1479:1525 Knockdown of NUP153, an O-GlcNAcylation target, has similar effects as OGT inhibition and inhibits osteoclastogenesis. 35879285 6 48 theme osteoclast 859:868 arg1 differentiation 870:884 osteoclast differentiation 859:884 osteoclast differentiation 859:884 Increased O-GlcNAcylation promotes osteoclast differentiation during the early stages, whereas its downregulation is required for osteoclast maturation. 35879285 3 49 theme posttranslational 424:440 arg1 modification 442:453 a posttranslational modification 422:453 a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins 422:584 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 3 49 theme posttranslational 424:440 arg1 O-GlcNAcylation 403:417 O-GlcNAcylation 403:417 O-GlcNAcylation 403:417 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 4 50 from role 665:668 arg1 homeostasis 678:688 bone homeostasis 673:688 bone homeostasis 673:688 Although O-GlcNAcylation is one of the most common protein modifications, its role in bone homeostasis has not been systematically investigated. 35879285 9 51 theme O-GlcNAcase 1291:1301 arg1 inhibition 1247:1256 Targeted pharmaceutical or genetic inhibition 1212:1256 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) 1212:1307 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 5 52 from changes 760:766 arg1 O-GlcNAcylation 771:785 O-GlcNAcylation 771:785 O-GlcNAcylation 771:785 We demonstrate that dynamic changes in O-GlcNAcylation are required for osteoclastogenesis. 35879285 2 53 theme inflammatory 232:243 arg1 arthritis 245:253 inflammatory arthritis 232:253 inflammatory arthritis such as rheumatoid arthritis (RA) 232:287 In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. 35879285 10 54 theme O-GlcNAcylation 1503:1517 arg1 target 1519:1524 an O-GlcNAcylation target 1500:1524 an O-GlcNAcylation target 1500:1524 Knockdown of NUP153, an O-GlcNAcylation target, has similar effects as OGT inhibition and inhibits osteoclastogenesis. 35879285 10 54 theme O-GlcNAcylation 1503:1517 arg1 NUP153 1492:1497 NUP153 1492:1497 NUP153 1492:1497 Knockdown of NUP153, an O-GlcNAcylation target, has similar effects as OGT inhibition and inhibits osteoclastogenesis. 35879285 7 55 theme several 1025:1031 arg1 phosphorylation 1062:1076 oxidative phosphorylation 1052:1076 oxidative phosphorylation 1052:1076 At the molecular level, O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell fusion. 35879285 7 55 theme several 1025:1031 arg1 fusion 1092:1097 cell-cell fusion 1082:1097 cell-cell fusion 1082:1097 At the molecular level, O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell fusion. 35879285 7 55 theme several 1025:1031 arg1 pathways 1033:1040 several pathways 1025:1040 several pathways including oxidative phosphorylation and cell-cell fusion 1025:1097 At the molecular level, O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell fusion. 35879285 9 56 theme later 1394:1398 arg1 maturation 1400:1409 later maturation 1394:1409 later maturation 1394:1409 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 6 57 theme early 897:901 arg1 stages 903:908 the early stages 893:908 the early stages 893:908 Increased O-GlcNAcylation promotes osteoclast differentiation during the early stages, whereas its downregulation is required for osteoclast maturation. 35879285 6 58 theme Increased 824:832 arg1 O-GlcNAcylation 834:848 Increased O-GlcNAcylation 824:848 Increased O-GlcNAcylation 824:848 Increased O-GlcNAcylation promotes osteoclast differentiation during the early stages, whereas its downregulation is required for osteoclast maturation. 35879285 3 59 theme residue 527:533 arg1 attachment 460:469 attachment 460:469 attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins 460:584 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 10 60 theme similar 1531:1537 arg1 effects 1539:1545 similar effects 1531:1545 similar effects 1531:1545 Knockdown of NUP153, an O-GlcNAcylation target, has similar effects as OGT inhibition and inhibits osteoclastogenesis. 35879285 5 61 theme dynamic 752:758 arg1 changes 760:766 dynamic changes 752:766 dynamic changes in O-GlcNAcylation 752:785 We demonstrate that dynamic changes in O-GlcNAcylation are required for osteoclastogenesis. 35879285 9 62 theme bone 1442:1445 arg1 loss 1447:1450 bone loss 1442:1450 bone loss in experimental arthritis 1442:1476 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 2 63 theme bone 392:395 arg1 loss 397:400 progressive bone loss 380:400 progressive bone loss 380:400 In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. 35879285 7 64 theme molecular 984:992 arg1 level 994:998 the molecular level 980:998 the molecular level 980:998 At the molecular level, O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell fusion. 35879285 3 65 theme O-GlcNAc 517:524 arg1 residue 527:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue 474:533 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 35879285 0 66 theme bone 75:78 arg1 loss 80:83 bone loss 75:83 bone loss 75:83 Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153. 35879285 9 67 from loss 1447:1450 arg1 arthritis 1468:1476 experimental arthritis 1455:1476 experimental arthritis 1455:1476 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 9 68 theme osteoclast 1317:1326 arg1 differentiation 1328:1342 osteoclast differentiation 1317:1342 osteoclast differentiation 1317:1342 Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. 35879285 3 69 theme target 570:575 arg1 proteins 577:584 target proteins 570:584 target proteins 570:584 O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. 36499281 6 0 theme scaffold 1263:1270 arg1 protein 1272:1278 a highly conserved cytoplasmic scaffold protein 1232:1278 a highly conserved cytoplasmic scaffold protein 1232:1278 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 6 1 theme activating 1157:1166 arg1 IQGAP1 1176:1181 the GTPase activating protein IQGAP1 1146:1181 the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1146:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 6 1 theme activating 1157:1166 arg1 protein 1222:1228 IQ motif-containing GTPase activating protein 1184:1228 IQ motif-containing GTPase activating protein 1184:1228 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 9 2 theme Lec4 1655:1658 arg1 cells 1660:1664 Lec1 and Lec4 cells 1646:1664 cells 1660:1664 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 3 3 theme proteome 716:723 arg1 analysis 725:732 proteome analysis 716:732 proteome analysis 716:732 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 6 4 theme conserved 1241:1249 arg1 protein 1272:1278 a highly conserved cytoplasmic scaffold protein 1232:1278 a highly conserved cytoplasmic scaffold protein 1232:1278 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 2 5 theme glycosylation 295:307 arg1 machinery 309:317 the glycosylation machinery 291:317 the glycosylation machinery 291:317 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 5 6 theme defective 894:902 arg1 mutants 920:926 The defective N-glycosylation mutants 890:926 The defective N-glycosylation mutants 890:926 The defective N-glycosylation mutants showed increased abundance of integrin subunits in Lec1 and Lec4 cells at the cell surface. 36499281 3 7 theme CHO 576:578 arg1 cells 580:584 Parent Pro-5 CHO cells 563:584 Parent Pro-5 CHO cells (W5 cells) 563:595 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 7 theme CHO 576:578 arg1 cells 590:594 W5 cells 587:594 W5 cells 587:594 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 1 8 theme inter- 175:180 arg1 recognition 261:271 cellular recognition 252:271 cellular recognition 252:271 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 1 8 theme inter- 175:180 arg1 development 235:245 development 235:245 development 235:245 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 1 8 theme inter- 175:180 arg1 processes 200:208 inter- and intracellular processes 175:208 inter- and intracellular processes including cell adhesion, development, and cellular recognition 175:271 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 1 8 theme inter- 175:180 arg1 adhesion 225:232 cell adhesion 220:232 cell adhesion 220:232 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 9 9 theme IGF-1 1700:1704 arg1 stimulation 1711:1721 IGF-1R ligand (IGF-1 LR3) stimulation 1685:1721 IGF-1R ligand (IGF-1 LR3) stimulation 1685:1721 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 11 10 theme IGF-1R-associated 1987:2003 arg1 IQGAP1 1954:1959 wherein IQGAP1 1946:1959 wherein IQGAP1 1946:1959 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 11 10 theme IGF-1R-associated 1987:2003 arg1 protein 2014:2020 an IGF-1R-associated scaffold protein 1984:2020 an IGF-1R-associated scaffold protein 1984:2020 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 1 11 theme intracellular 186:198 arg1 recognition 261:271 cellular recognition 252:271 cellular recognition 252:271 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 1 11 theme intracellular 186:198 arg1 development 235:245 development 235:245 development 235:245 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 1 11 theme intracellular 186:198 arg1 processes 200:208 inter- and intracellular processes 175:208 inter- and intracellular processes including cell adhesion, development, and cellular recognition 175:271 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 1 11 theme intracellular 186:198 arg1 adhesion 225:232 cell adhesion 220:232 cell adhesion 220:232 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 6 12 theme tyrosine 1125:1132 arg1 kinase 1134:1139 a receptor tyrosine kinase 1114:1139 a receptor tyrosine kinase 1114:1139 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 12 13 from partner 2166:2172 arg1 signaling 2192:2200 IQGAP1 and ERK signaling 2177:2200 signaling 2192:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 1 14 theme surface 115:121 arg1 proteins 123:130 Cell surface proteins 110:130 Cell surface proteins carrying N-glycans 110:149 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 9 15 theme IGF-1R 1685:1690 arg1 stimulation 1711:1721 IGF-1R ligand (IGF-1 LR3) stimulation 1685:1721 IGF-1R ligand (IGF-1 LR3) stimulation 1685:1721 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 7 16 theme IQ 1347:1348 arg1 IQGAP1 1360:1365 IQGAP1 1360:1365 IQGAP1 1360:1365 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 7 16 theme IQ 1347:1348 arg1 domain 1350:1355 the IQ domain 1343:1355 the IQ domain of IQGAP1 1343:1365 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 6 17 theme Lec4 1293:1296 arg1 cells 1298:1302 Lec1 and Lec4 cells 1284:1302 cells 1298:1302 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 11 18 theme ERK 1918:1920 arg1 signaling 1922:1930 IGF-1 dependent ERK signaling 1902:1930 IGF-1 dependent ERK signaling 1902:1930 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 8 19 theme GSEA 1511:1514 arg1 analysis 1516:1523 GSEA analysis 1511:1523 GSEA analysis 1511:1523 The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. 36499281 6 20 theme GTPase 1204:1209 arg1 IQGAP1 1176:1181 the GTPase activating protein IQGAP1 1146:1181 the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1146:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 6 20 theme GTPase 1204:1209 arg1 protein 1222:1228 IQ motif-containing GTPase activating protein 1184:1228 IQ motif-containing GTPase activating protein 1184:1228 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 6 21 dep IQGAP1 1176:1181 arg1 protein 1272:1278 a highly conserved cytoplasmic scaffold protein 1232:1278 a highly conserved cytoplasmic scaffold protein 1232:1278 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 6 22 theme Lec1 1284:1287 arg1 cells 1298:1302 Lec1 and Lec4 cells 1284:1302 cells 1298:1302 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 3 23 theme CHO 602:604 arg1 mutants 606:612 two CHO mutants 598:612 two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells) 598:695 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 23 theme CHO 602:604 arg1 proteins 540:547 Cell surface proteins 527:547 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells) 527:595 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 5 24 theme N-glycosylation 904:918 arg1 mutants 920:926 The defective N-glycosylation mutants 890:926 The defective N-glycosylation mutants 890:926 The defective N-glycosylation mutants showed increased abundance of integrin subunits in Lec1 and Lec4 cells at the cell surface. 36499281 9 25 from ERK2 1638:1641 arg1 cells 1660:1664 Lec1 and Lec4 cells 1646:1664 cells 1660:1664 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 9 26 theme LR3 1706:1708 arg1 stimulation 1711:1721 IGF-1R ligand (IGF-1 LR3) stimulation 1685:1721 IGF-1R ligand (IGF-1 LR3) stimulation 1685:1721 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 10 27 theme lengthened 1793:1802 arg1 analog 1804:1809 lengthened analog 1793:1809 lengthened analog of insulin-like growth factor 1 1793:1841 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 6 28 theme IQ 1184:1185 arg1 IQGAP1 1176:1181 the GTPase activating protein IQGAP1 1146:1181 the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1146:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 6 28 theme IQ 1184:1185 arg1 protein 1222:1228 IQ motif-containing GTPase activating protein 1184:1228 IQ motif-containing GTPase activating protein 1184:1228 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 11 29 from activation 1888:1897 arg1 cells 1939:1943 CHO cells 1935:1943 CHO cells 1935:1943 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 3 30 theme function 643:650 arg1 loss 619:622 loss 619:622 loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells) 619:695 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 8 31 theme insulin 1438:1444 arg1 signaling 1469:1477 insulin growth factor receptor signaling 1438:1477 insulin growth factor receptor signaling 1438:1477 The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. 36499281 6 32 theme IQGAP1 1176:1181 arg1 levels 1056:1061 significantly reduced levels 1034:1061 significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1034:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 12 33 gly glycosylation 2035:2047 arg1 partner 2166:2172 a potential binding partner 2146:2172 a potential binding partner in IQGAP1 and ERK signaling 2146:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 33 gly glycosylation 2035:2047 arg1 IGF-1R 2138:2143 cell surface receptor IGF-1R 2116:2143 cell surface receptor IGF-1R 2116:2143 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 10 34 theme synthetic 1771:1779 arg1 protein 1781:1787 a synthetic protein 1769:1787 a synthetic protein 1769:1787 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 10 34 theme synthetic 1771:1779 arg1 LR3 1730:1732 IGF-1 LR3 1724:1732 IGF-1 LR3 1724:1732 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 8 35 theme factor 1453:1458 arg1 signaling 1469:1477 insulin growth factor receptor signaling 1438:1477 insulin growth factor receptor signaling 1438:1477 The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. 36499281 12 36 theme Appropriate 2023:2033 arg1 glycosylation 2035:2047 Appropriate glycosylation 2023:2047 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 2023:2078 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 0 37 theme Insulin-like 70:81 arg1 Factor 90:95 Insulin-like Growth Factor 1 70:97 Insulin-like Growth Factor 1 Signaling 70:107 N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling. 36499281 12 38 theme pathway 2238:2244 arg1 components 2216:2225 the integral components 2203:2225 the integral components of the IGF pathway 2203:2244 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 38 theme pathway 2238:2244 arg1 partner 2166:2172 a potential binding partner 2146:2172 a potential binding partner in IQGAP1 and ERK signaling 2146:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 39 theme ERK 2188:2190 arg1 signaling 2192:2200 IQGAP1 and ERK signaling 2177:2200 signaling 2192:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 0 40 theme Factor 90:95 arg1 Signaling 99:107 Insulin-like Growth Factor 1 Signaling 70:107 Insulin-like Growth Factor 1 Signaling 70:107 N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling. 36499281 10 41 theme IGF-1 1724:1728 arg1 protein 1781:1787 a synthetic protein 1769:1787 a synthetic protein 1769:1787 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 10 41 theme IGF-1 1724:1728 arg1 LR3 1730:1732 IGF-1 LR3 1724:1732 IGF-1 LR3 1724:1732 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 2 42 theme effects 423:429 arg1 investigation 364:376 investigation 364:376 investigation of global differential cell surface proteome effects due to the loss of N-glycosylation 364:464 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 6 43 theme IGF-1R 1066:1071 arg1 levels 1056:1061 significantly reduced levels 1034:1061 significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1034:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 2 44 theme surface 406:412 arg1 effects 423:429 global differential cell surface proteome effects 381:429 global differential cell surface proteome effects due to the loss of N-glycosylation 381:464 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 0 45 theme N-Linked 0:7 arg1 Glycosylation 9:21 N-Linked Glycosylation 0:21 N-Linked Glycosylation in Chinese Hamster Ovary Cells 0:52 N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling. 36499281 2 46 theme N-glycosylation 450:464 arg1 loss 442:445 the loss 438:445 the loss of N-glycosylation 438:464 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 2 47 theme global 381:386 arg1 effects 423:429 global differential cell surface proteome effects 381:429 global differential cell surface proteome effects due to the loss of N-glycosylation 381:464 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 12 48 theme IQGAP1 2177:2182 arg1 signaling 2192:2200 IQGAP1 and ERK signaling 2177:2200 signaling 2192:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 5 49 theme integrin 958:965 arg1 subunits 967:974 integrin subunits 958:974 integrin subunits 958:974 The defective N-glycosylation mutants showed increased abundance of integrin subunits in Lec1 and Lec4 cells at the cell surface. 36499281 10 50 theme insulin-like 1814:1825 arg1 factor 1834:1839 insulin-like growth factor 1 1814:1841 insulin-like growth factor 1 1814:1841 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 0 51 theme Hamster 34:40 arg1 Cells 48:52 Chinese Hamster Ovary Cells 26:52 Chinese Hamster Ovary Cells 26:52 N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling. 36499281 11 52 dep suggests 1853:1860 arg1 functions 1971:1979 functions 1971:1979 functions as an IGF-1R-associated scaffold protein 1971:2020 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 12 53 theme potential 2148:2156 arg1 components 2216:2225 the integral components 2203:2225 the integral components of the IGF pathway 2203:2244 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 53 theme potential 2148:2156 arg1 partner 2166:2172 a potential binding partner 2146:2172 a potential binding partner in IQGAP1 and ERK signaling 2146:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 53 theme potential 2148:2156 arg1 IGF-1R 2138:2143 cell surface receptor IGF-1R 2116:2143 cell surface receptor IGF-1R 2116:2143 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 3 54 theme Cell 527:530 arg1 mutants 606:612 two CHO mutants 598:612 two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells) 598:695 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 54 theme Cell 527:530 arg1 proteins 540:547 Cell surface proteins 527:547 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells) 527:595 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 12 55 theme IGF 2234:2236 arg1 pathway 2238:2244 the IGF pathway 2230:2244 the IGF pathway 2230:2244 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 7 56 dep In 1305:1306 arg1 silico 1308:1313 silico 1308:1313 silico 1308:1313 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 3 57 attach isolated 549:556 arg1 cells 580:584 Parent Pro-5 CHO cells 563:584 Parent Pro-5 CHO cells (W5 cells) 563:595 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 57 attach isolated 549:556 arg1 cells 590:594 W5 cells 587:594 W5 cells 587:594 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 57 attach isolated 549:556 arg2 proteins 540:547 Cell surface proteins 527:547 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells) 527:595 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 57 attach isolated 549:556 arg2 mutants 606:612 two CHO mutants 598:612 two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells) 598:695 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 6 58 theme protein 1168:1174 arg1 IQGAP1 1176:1181 the GTPase activating protein IQGAP1 1146:1181 the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1146:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 6 58 theme protein 1168:1174 arg1 protein 1222:1228 IQ motif-containing GTPase activating protein 1184:1228 IQ motif-containing GTPase activating protein 1184:1228 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 3 59 theme Lec4 685:688 arg1 cells 690:694 Lec4 cells 685:694 Lec4 cells 685:694 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 12 60 theme cell 2116:2119 arg1 partner 2166:2172 a potential binding partner 2146:2172 a potential binding partner in IQGAP1 and ERK signaling 2146:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 60 theme cell 2116:2119 arg1 IGF-1R 2138:2143 cell surface receptor IGF-1R 2116:2143 cell surface receptor IGF-1R 2116:2143 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 61 dep enzymes 2056:2062 arg1 MGAT5 2074:2078 MGAT5 2074:2078 MGAT5 2074:2078 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 61 dep enzymes 2056:2062 arg1 MGAT1 2064:2068 MGAT1 2064:2068 MGAT1 2064:2068 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 61 dep enzymes 2056:2062 arg1 enzymes 2056:2062 the enzymes MGAT1 and MGAT5 2052:2078 the enzymes MGAT1 and MGAT5 2052:2078 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 11 62 theme wherein 1946:1952 arg1 IQGAP1 1954:1959 wherein IQGAP1 1946:1959 wherein IQGAP1 1946:1959 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 11 62 theme wherein 1946:1952 arg1 protein 2014:2020 an IGF-1R-associated scaffold protein 1984:2020 an IGF-1R-associated scaffold protein 1984:2020 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 9 63 theme phosphorylation 1610:1624 arg1 reductions 1596:1605 Significant reductions 1584:1605 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells 1584:1664 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 8 64 theme proteins 1574:1581 arg1 analysis 1516:1523 GSEA analysis 1511:1523 GSEA analysis 1511:1523 The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. 36499281 8 64 theme proteins 1574:1581 arg1 analysis 1537:1544 pathway analysis 1529:1544 pathway analysis 1529:1544 The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. 36499281 10 65 theme factor 1834:1839 arg1 protein 1781:1787 a synthetic protein 1769:1787 a synthetic protein 1769:1787 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 10 65 theme factor 1834:1839 arg1 analog 1804:1809 lengthened analog 1793:1809 lengthened analog of insulin-like growth factor 1 1793:1841 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 10 65 theme factor 1834:1839 arg1 LR3 1730:1732 IGF-1 LR3 1724:1732 IGF-1 LR3 1724:1732 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 4 66 theme membrane 809:816 arg1 proteins 818:825 44 and 43 differentially expressed membrane proteins 774:825 44 and 43 differentially expressed membrane proteins 774:825 We identified 44 and 43 differentially expressed membrane proteins in Lec1 and Lec4 cells, respectively, as compared to W5 cells. 36499281 2 67 theme differential 388:399 arg1 effects 423:429 global differential cell surface proteome effects 381:429 global differential cell surface proteome effects due to the loss of N-glycosylation 381:464 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 5 68 from abundance 945:953 arg1 cells 993:997 Lec1 and Lec4 cells 979:997 cells 993:997 The defective N-glycosylation mutants showed increased abundance of integrin subunits in Lec1 and Lec4 cells at the cell surface. 36499281 3 69 dep Pro-5 665:669 arg1 CHO 671:673 CHO 671:673 Pro-5 CHO (Lec1 and Lec4 cells) 665:695 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 9 70 theme ERK1 1629:1632 arg1 phosphorylation 1610:1624 phosphorylation 1610:1624 phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells 1610:1664 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 6 71 theme growth 1087:1092 arg1 receptor 1103:1110 growth factor-1 receptor 1087:1110 growth factor-1 receptor 1087:1110 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 1 72 theme cellular 252:259 arg1 recognition 261:271 cellular recognition 252:271 cellular recognition 252:271 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 9 73 theme ERK2 1638:1641 arg1 phosphorylation 1610:1624 phosphorylation 1610:1624 phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells 1610:1664 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 6 74 theme cytoplasmic 1251:1261 arg1 protein 1272:1278 a highly conserved cytoplasmic scaffold protein 1232:1278 a highly conserved cytoplasmic scaffold protein 1232:1278 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 11 75 theme novel 1864:1868 arg1 mechanism 1870:1878 a novel mechanism 1862:1878 a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells 1862:1943 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 2 76 theme machinery 309:317 arg1 Dysregulation 274:286 Dysregulation 274:286 Dysregulation of the glycosylation machinery 274:317 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 9 77 theme Lec1 1646:1649 arg1 cells 1660:1664 Lec1 and Lec4 cells 1646:1664 cells 1660:1664 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 6 78 theme GTPase 1150:1155 arg1 IQGAP1 1176:1181 the GTPase activating protein IQGAP1 1146:1181 the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1146:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 6 78 theme GTPase 1150:1155 arg1 protein 1222:1228 IQ motif-containing GTPase activating protein 1184:1228 IQ motif-containing GTPase activating protein 1184:1228 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 3 79 theme Pro-5 570:574 arg1 cells 580:584 Parent Pro-5 CHO cells 563:584 Parent Pro-5 CHO cells (W5 cells) 563:595 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 79 theme Pro-5 570:574 arg1 cells 590:594 W5 cells 587:594 W5 cells 587:594 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 7 80 theme IGF-1R 1403:1408 arg1 IGF-1R 1403:1408 IGF-1R 1403:1408 IGF-1R 1403:1408 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 7 80 theme IGF-1R 1403:1408 arg1 domain 1393:1398 the kinase domain 1382:1398 the kinase domain of IGF-1R 1382:1408 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 4 81 theme Lec4 839:842 arg1 cells 844:848 Lec1 and Lec4 cells 830:848 cells 844:848 We identified 44 and 43 differentially expressed membrane proteins in Lec1 and Lec4 cells, respectively, as compared to W5 cells. 36499281 7 82 theme kinase 1386:1391 arg1 IGF-1R 1403:1408 IGF-1R 1403:1408 IGF-1R 1403:1408 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 7 82 theme kinase 1386:1391 arg1 domain 1393:1398 the kinase domain 1382:1398 the kinase domain of IGF-1R 1382:1408 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 10 83 theme Long 1744:1747 arg1 arginine3-IGF-1 1749:1763 Long arginine3-IGF-1 1744:1763 Long arginine3-IGF-1 1744:1763 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 9 84 from cells 1660:1664 arg1 phosphorylation 1610:1624 phosphorylation 1610:1624 phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells 1610:1664 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 6 85 theme kinase 1134:1139 arg1 levels 1056:1061 significantly reduced levels 1034:1061 significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1034:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 3 86 theme W5 587:588 arg1 cells 580:584 Parent Pro-5 CHO cells 563:584 Parent Pro-5 CHO cells (W5 cells) 563:595 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 86 theme W5 587:588 arg1 cells 590:594 W5 cells 587:594 W5 cells 587:594 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 6 87 theme receptor 1116:1123 arg1 kinase 1134:1139 a receptor tyrosine kinase 1114:1139 a receptor tyrosine kinase 1114:1139 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 3 88 theme high-resolution 738:752 arg1 LCMS 754:757 high-resolution LCMS 738:757 high-resolution LCMS 738:757 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 11 89 theme dependent 1908:1916 arg1 signaling 1922:1930 IGF-1 dependent ERK signaling 1902:1930 IGF-1 dependent ERK signaling 1902:1930 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 1 90 theme cell 220:223 arg1 adhesion 225:232 cell adhesion 220:232 cell adhesion 220:232 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 9 91 theme ligand 1692:1697 arg1 stimulation 1711:1721 IGF-1R ligand (IGF-1 LR3) stimulation 1685:1721 IGF-1R ligand (IGF-1 LR3) stimulation 1685:1721 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 8 92 theme integrin 1415:1422 arg1 signaling 1424:1432 The integrin signaling 1411:1432 The integrin signaling 1411:1432 The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. 36499281 6 93 theme activating 1211:1220 arg1 IQGAP1 1176:1181 the GTPase activating protein IQGAP1 1146:1181 the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1146:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 6 93 theme activating 1211:1220 arg1 protein 1222:1228 IQ motif-containing GTPase activating protein 1184:1228 IQ motif-containing GTPase activating protein 1184:1228 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 11 94 theme CHO 1935:1937 arg1 cells 1939:1943 CHO cells 1935:1943 CHO cells 1935:1943 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 1 95 theme Cell 110:113 arg1 proteins 123:130 Cell surface proteins 110:130 Cell surface proteins carrying N-glycans 110:149 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 3 96 attach derived 652:658 arg2 function 643:650 N-glycosylation function 627:650 N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells) 627:695 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 96 attach derived 652:658 arg1 Pro-5 665:669 Pro-5 CHO (Lec1 and Lec4 cells) 665:695 Pro-5 CHO (Lec1 and Lec4 cells) 665:695 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 4 97 theme W5 880:881 arg1 cells 883:887 W5 cells 880:887 W5 cells 880:887 We identified 44 and 43 differentially expressed membrane proteins in Lec1 and Lec4 cells, respectively, as compared to W5 cells. 36499281 6 98 theme motif-containing 1187:1202 arg1 IQGAP1 1176:1181 the GTPase activating protein IQGAP1 1146:1181 the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1146:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 6 98 theme motif-containing 1187:1202 arg1 protein 1222:1228 IQ motif-containing GTPase activating protein 1184:1228 IQ motif-containing GTPase activating protein 1184:1228 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 3 99 theme N-glycosylation 627:641 arg1 function 643:650 N-glycosylation function 627:650 N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells) 627:695 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 8 100 theme growth 1446:1451 arg1 signaling 1469:1477 insulin growth factor receptor signaling 1438:1477 insulin growth factor receptor signaling 1438:1477 The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. 36499281 11 101 theme signaling 1922:1930 arg1 activation 1888:1897 the activation 1884:1897 the activation of IGF-1 dependent ERK signaling in CHO cells 1884:1943 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 8 102 theme receptor 1460:1467 arg1 signaling 1469:1477 insulin growth factor receptor signaling 1438:1477 insulin growth factor receptor signaling 1438:1477 The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. 36499281 7 103 theme docking 1315:1321 arg1 studies 1323:1329 In silico docking studies 1305:1329 In silico docking studies 1305:1329 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 0 104 theme Growth 83:88 arg1 Factor 90:95 Insulin-like Growth Factor 1 70:97 Insulin-like Growth Factor 1 Signaling 70:107 N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling. 36499281 1 105 theme important 156:164 arg1 roles 166:170 important roles 156:170 important roles 156:170 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 0 106 from Glycosylation 9:21 arg1 Cells 48:52 Chinese Hamster Ovary Cells 26:52 Chinese Hamster Ovary Cells 26:52 N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling. 36499281 5 107 theme subunits 967:974 arg1 abundance 945:953 increased abundance 935:953 increased abundance of integrin subunits in Lec1 and Lec4 cells 935:997 The defective N-glycosylation mutants showed increased abundance of integrin subunits in Lec1 and Lec4 cells at the cell surface. 36499281 7 108 theme IQGAP1 1360:1365 arg1 IQGAP1 1360:1365 IQGAP1 1360:1365 IQGAP1 1360:1365 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 7 108 theme IQGAP1 1360:1365 arg1 domain 1350:1355 the IQ domain 1343:1355 the IQ domain of IQGAP1 1343:1365 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 12 109 theme integral 2207:2214 arg1 components 2216:2225 the integral components 2203:2225 the integral components of the IGF pathway 2203:2244 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 109 theme integral 2207:2214 arg1 partner 2166:2172 a potential binding partner 2146:2172 a potential binding partner in IQGAP1 and ERK signaling 2146:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 3 110 with mutants 606:612 arg1 loss 619:622 loss 619:622 loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells) 619:695 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 5 111 theme Lec1 979:982 arg1 cells 993:997 Lec1 and Lec4 cells 979:997 cells 993:997 The defective N-glycosylation mutants showed increased abundance of integrin subunits in Lec1 and Lec4 cells at the cell surface. 36499281 9 112 from ERK1 1629:1632 arg1 cells 1660:1664 Lec1 and Lec4 cells 1646:1664 cells 1660:1664 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 2 113 theme proteome 414:421 arg1 effects 423:429 global differential cell surface proteome effects 381:429 global differential cell surface proteome effects due to the loss of N-glycosylation 381:464 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 5 114 theme increased 935:943 arg1 abundance 945:953 increased abundance 935:953 increased abundance of integrin subunits in Lec1 and Lec4 cells 935:997 The defective N-glycosylation mutants showed increased abundance of integrin subunits in Lec1 and Lec4 cells at the cell surface. 36499281 9 115 from phosphorylation 1610:1624 arg1 cells 1660:1664 Lec1 and Lec4 cells 1646:1664 cells 1660:1664 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 11 116 theme scaffold 2005:2012 arg1 IQGAP1 1954:1959 wherein IQGAP1 1946:1959 wherein IQGAP1 1946:1959 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 11 116 theme scaffold 2005:2012 arg1 protein 2014:2020 an IGF-1R-associated scaffold protein 1984:2020 an IGF-1R-associated scaffold protein 1984:2020 The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. 36499281 12 117 theme binding 2158:2164 arg1 components 2216:2225 the integral components 2203:2225 the integral components of the IGF pathway 2203:2244 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 117 theme binding 2158:2164 arg1 partner 2166:2172 a potential binding partner 2146:2172 a potential binding partner in IQGAP1 and ERK signaling 2146:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 117 theme binding 2158:2164 arg1 IGF-1R 2138:2143 cell surface receptor IGF-1R 2116:2143 cell surface receptor IGF-1R 2116:2143 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 2 118 theme cell 401:404 arg1 effects 423:429 global differential cell surface proteome effects 381:429 global differential cell surface proteome effects due to the loss of N-glycosylation 381:464 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 0 119 theme Chinese 26:32 arg1 Cells 48:52 Chinese Hamster Ovary Cells 26:52 Chinese Hamster Ovary Cells 26:52 N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling. 36499281 12 120 theme receptor 2129:2136 arg1 partner 2166:2172 a potential binding partner 2146:2172 a potential binding partner in IQGAP1 and ERK signaling 2146:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 120 theme receptor 2129:2136 arg1 IGF-1R 2138:2143 cell surface receptor IGF-1R 2116:2143 cell surface receptor IGF-1R 2116:2143 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 6 121 theme reduced 1048:1054 arg1 levels 1056:1061 significantly reduced levels 1034:1061 significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) 1034:1279 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 8 122 theme pathway 1529:1535 arg1 analysis 1537:1544 pathway analysis 1529:1544 pathway analysis 1529:1544 The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. 36499281 10 123 theme growth 1827:1832 arg1 factor 1834:1839 insulin-like growth factor 1 1814:1841 insulin-like growth factor 1 1814:1841 IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. 36499281 6 124 dep IGF-1R 1066:1071 arg1 Insulin 1074:1080 Insulin 1074:1080 Insulin like growth factor-1 receptor 1074:1110 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 0 125 theme Ovary 42:46 arg1 Cells 48:52 Chinese Hamster Ovary Cells 26:52 Chinese Hamster Ovary Cells 26:52 N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling. 36499281 5 126 theme cell 1006:1009 arg1 surface 1011:1017 the cell surface 1002:1017 the cell surface 1002:1017 The defective N-glycosylation mutants showed increased abundance of integrin subunits in Lec1 and Lec4 cells at the cell surface. 36499281 12 127 theme IGF-1R 2138:2143 arg1 processing 2102:2111 processing 2102:2111 processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway 2102:2244 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 2 128 theme due 431:433 arg1 effects 423:429 global differential cell surface proteome effects 381:429 global differential cell surface proteome effects due to the loss of N-glycosylation 381:464 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 9 129 theme Significant 1584:1594 arg1 reductions 1596:1605 Significant reductions 1584:1605 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells 1584:1664 Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. 36499281 2 130 theme comprehensive 479:491 arg1 insights 493:500 comprehensive insights 479:500 comprehensive insights into their pathogenesis 479:524 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 8 131 theme expressed 1564:1572 arg1 proteins 1574:1581 differentially expressed proteins 1549:1581 differentially expressed proteins 1549:1581 The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. 36499281 4 132 theme Lec1 830:833 arg1 cells 844:848 Lec1 and Lec4 cells 830:848 cells 844:848 We identified 44 and 43 differentially expressed membrane proteins in Lec1 and Lec4 cells, respectively, as compared to W5 cells. 36499281 3 133 theme surface 532:538 arg1 mutants 606:612 two CHO mutants 598:612 two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells) 598:695 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 133 theme surface 532:538 arg1 proteins 540:547 Cell surface proteins 527:547 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells) 527:595 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 12 134 theme surface 2121:2127 arg1 partner 2166:2172 a potential binding partner 2146:2172 a potential binding partner in IQGAP1 and ERK signaling 2146:2200 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 12 134 theme surface 2121:2127 arg1 IGF-1R 2138:2143 cell surface receptor IGF-1R 2116:2143 cell surface receptor IGF-1R 2116:2143 Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway. 36499281 5 135 theme Lec4 988:991 arg1 cells 993:997 Lec1 and Lec4 cells 979:997 cells 993:997 The defective N-glycosylation mutants showed increased abundance of integrin subunits in Lec1 and Lec4 cells at the cell surface. 36499281 2 136 theme various 342:348 arg1 diseases 350:357 various diseases 342:357 various diseases 342:357 Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. 36499281 6 137 theme factor-1 1094:1101 arg1 receptor 1103:1110 growth factor-1 receptor 1087:1110 growth factor-1 receptor 1087:1110 We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. 36499281 7 138 theme In 1305:1306 arg1 studies 1323:1329 In silico docking studies 1305:1329 In silico docking studies 1305:1329 In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. 36499281 1 139 contain carrying 132:139 arg1 proteins 123:130 Cell surface proteins 110:130 Cell surface proteins carrying N-glycans 110:149 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 1 139 contain carrying 132:139 arg2 N-glycans 141:149 N-glycans 141:149 N-glycans 141:149 Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. 36499281 4 140 theme expressed 799:807 arg1 proteins 818:825 44 and 43 differentially expressed membrane proteins 774:825 44 and 43 differentially expressed membrane proteins 774:825 We identified 44 and 43 differentially expressed membrane proteins in Lec1 and Lec4 cells, respectively, as compared to W5 cells. 36499281 3 141 theme Parent 563:568 arg1 cells 580:584 Parent Pro-5 CHO cells 563:584 Parent Pro-5 CHO cells (W5 cells) 563:595 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 141 theme Parent 563:568 arg1 cells 590:594 W5 cells 587:594 W5 cells 587:594 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 142 dep CHO 671:673 arg1 Lec1 676:679 Lec1 676:679 Lec1 676:679 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36499281 3 142 dep CHO 671:673 arg1 cells 690:694 Lec4 cells 685:694 Lec4 cells 685:694 Cell surface proteins isolated from Parent Pro-5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro-5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. 36395347 6 0 theme different 904:912 arg1 clades 914:919 different clades 904:919 different clades 904:919 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 9 1 theme NAbs 1611:1614 arg1 combinations 1578:1589 combinations 1578:1589 combinations of moderately broad NAbs 1578:1614 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 4 2 theme HIV-1 494:498 arg1 Env 524:526 Env 524:526 Env 524:526 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 4 2 theme HIV-1 494:498 arg1 glycoproteins 509:521 HIV-1 envelope glycoproteins 494:521 HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells 494:549 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 6 3 theme strains 891:897 arg1 set 878:880 a diverse set 868:880 a diverse set of HIV-1 strains from different clades 868:919 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 3 theme strains 891:897 arg1 strains 891:897 HIV-1 strains 885:897 HIV-1 strains from different clades 885:919 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 4 4 attach isolated 556:563 arg2 Env 524:526 Env 524:526 Env 524:526 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 4 4 attach isolated 556:563 arg2 glycoproteins 509:521 HIV-1 envelope glycoproteins 494:521 HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells 494:549 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 4 4 attach isolated 556:563 arg1 neutralizer 632:642 an HIV-1 infected elite neutralizer 608:642 an HIV-1 infected elite neutralizer 608:642 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 4 5 gly glycoproteins 509:521 arg1 Env 524:526 Env 524:526 Env 524:526 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 4 5 gly glycoproteins 509:521 arg1 glycoproteins 509:521 HIV-1 envelope glycoproteins 494:521 HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells 494:549 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 9 6 theme viable 1627:1632 arg1 induction 1565:1573 the induction 1561:1573 the induction of combinations of moderately broad NAbs 1561:1614 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 9 6 theme viable 1627:1632 arg1 strategy 1642:1649 a viable vaccine strategy 1625:1649 a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses 1625:1710 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 7 7 theme cryo-electron 1090:1102 arg1 microscopy 1104:1113 High-resolution cryo-electron microscopy 1074:1113 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual 1074:1221 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 0 8 theme Complementary 0:12 arg1 lineages 23:30 Complementary antibody lineages 0:30 Complementary antibody lineages 0:30 Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer. 36395347 1 9 theme most 187:190 arg1 subtypes 198:205 most HIV-1 subtypes 187:205 most HIV-1 subtypes 187:205 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 6 10 theme diverse 870:876 arg1 set 878:880 a diverse set 868:880 a diverse set of HIV-1 strains from different clades 868:919 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 10 theme diverse 870:876 arg1 strains 891:897 HIV-1 strains 885:897 HIV-1 strains from different clades 885:919 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 11 theme serum 962:966 arg1 result 1008:1013 the result 1004:1013 the result of a polyclonal mixture rather than a single bNAb lineage 1004:1071 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 11 theme serum 962:966 arg1 potency 980:986 potency 980:986 potency 980:986 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 11 theme serum 962:966 arg1 breadth 968:974 the patient's remarkable serum breadth 937:974 the patient's remarkable serum breadth 937:974 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 7 12 with complex 1161:1167 arg1 trimer 1181:1186 an Env trimer 1174:1186 an Env trimer generated from the same individual 1174:1221 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 7 13 theme N-linked 1353:1360 arg1 glycans 1362:1368 HIV-1 Env N-linked glycans 1343:1368 HIV-1 Env N-linked glycans 1343:1368 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 7 14 theme HIV-1 1343:1347 arg1 glycans 1362:1368 HIV-1 Env N-linked glycans 1343:1368 HIV-1 Env N-linked glycans 1343:1368 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 8 15 from response 1514:1521 arg1 individuals 1541:1551 HIV-1 infected individuals 1526:1551 HIV-1 infected individuals 1526:1551 These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. 36395347 9 16 theme circulating 1686:1696 arg1 viruses 1704:1710 circulating HIV-1 viruses 1686:1710 circulating HIV-1 viruses 1686:1710 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 5 17 theme antibody 693:700 arg1 lineages 702:709 Multiple antibody lineages 684:709 Multiple antibody lineages 684:709 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 9 18 theme viruses 1704:1710 arg1 range 1677:1681 a wide range 1670:1681 a wide range of circulating HIV-1 viruses 1670:1710 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 0 19 theme HIV-1 69:73 arg1 neutralizer 90:100 an HIV-1 infected elite neutralizer 66:100 an HIV-1 infected elite neutralizer 66:100 Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer. 36395347 4 20 theme various 568:574 arg1 points 581:586 various time points 568:586 various time points post infection 568:601 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 0 21 theme elite 84:88 arg1 neutralizer 90:100 an HIV-1 infected elite neutralizer 66:100 an HIV-1 infected elite neutralizer 66:100 Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer. 36395347 3 22 theme developmental 343:355 arg1 pathways 357:364 the developmental pathways 339:364 the developmental pathways towards neutralization breadth 339:395 Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. 36395347 8 23 theme broad 1478:1482 arg1 response 1514:1521 a broad and potent neutralizing serum response 1476:1521 a broad and potent neutralizing serum response in HIV-1 infected individuals 1476:1551 These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. 36395347 3 24 theme protective 446:455 arg1 responses 462:470 protective bNAb responses 446:470 protective bNAb responses 446:470 Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. 36395347 7 25 theme Env 1177:1179 arg1 trimer 1181:1186 an Env trimer 1174:1186 an Env trimer generated from the same individual 1174:1221 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 6 26 theme single 1053:1058 arg1 lineage 1065:1071 a single bNAb lineage 1051:1071 a polyclonal mixture rather than a single bNAb lineage 1018:1071 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 8 27 theme potent 1488:1493 arg1 response 1514:1521 a broad and potent neutralizing serum response 1476:1521 a broad and potent neutralizing serum response in HIV-1 infected individuals 1476:1551 These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. 36395347 0 28 theme infected 75:82 arg1 neutralizer 90:100 an HIV-1 infected elite neutralizer 66:100 an HIV-1 infected elite neutralizer 66:100 Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer. 36395347 5 29 theme silent 815:820 arg1 interface 786:794 the gp120-gp41 interface 771:794 the gp120-gp41 interface 771:794 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 5 29 theme silent 815:820 arg1 face 822:825 silent face 815:825 silent face 815:825 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 5 29 theme silent 815:820 arg1 epitopes 744:751 distinct epitopes 735:751 distinct epitopes 735:751 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 8 30 theme serum 1508:1512 arg1 response 1514:1521 a broad and potent neutralizing serum response 1476:1521 a broad and potent neutralizing serum response in HIV-1 infected individuals 1476:1551 These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. 36395347 6 31 theme mixture 1031:1037 arg1 result 1008:1013 the result 1004:1013 the result of a polyclonal mixture rather than a single bNAb lineage 1004:1071 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 31 theme mixture 1031:1037 arg1 potency 980:986 potency 980:986 potency 980:986 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 31 theme mixture 1031:1037 arg1 breadth 968:974 the patient's remarkable serum breadth 937:974 the patient's remarkable serum breadth 937:974 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 0 32 theme neutralization 40:53 arg1 breadth 55:61 neutralization breadth 40:61 neutralization breadth 40:61 Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer. 36395347 7 33 link N-linked 1353:1360 arg1 glycans 1362:1368 HIV-1 Env N-linked glycans 1343:1368 HIV-1 Env N-linked glycans 1343:1368 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 8 34 theme infected 1532:1539 arg1 individuals 1541:1551 HIV-1 infected individuals 1526:1551 HIV-1 infected individuals 1526:1551 These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. 36395347 7 35 theme mAbs 1146:1149 arg1 structures 1115:1124 High-resolution cryo-electron microscopy structures 1074:1124 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual 1074:1221 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 6 36 dep mAbs 846:849 arg1 each 851:854 each 851:854 each 851:854 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 4 37 theme B 543:543 arg1 cells 545:549 -specific IgG+ B cells 528:549 HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells 494:549 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 7 38 theme multiple 1251:1258 arg1 strategies 1260:1269 multiple strategies 1251:1269 multiple strategies 1251:1269 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 5 39 theme CD4-binding 797:807 arg1 interface 786:794 the gp120-gp41 interface 771:794 the gp120-gp41 interface 771:794 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 5 39 theme CD4-binding 797:807 arg1 site 809:812 CD4-binding site 797:812 CD4-binding site 797:812 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 5 39 theme CD4-binding 797:807 arg1 epitopes 744:751 distinct epitopes 735:751 distinct epitopes 735:751 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 9 40 theme broad 1605:1609 arg1 NAbs 1611:1614 moderately broad NAbs 1594:1614 moderately broad NAbs 1594:1614 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 7 41 from structures 1115:1124 arg1 complex 1161:1167 complex 1161:1167 complex with an Env trimer generated from the same individual 1161:1221 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 6 42 from clades 914:919 arg1 set 878:880 a diverse set 868:880 a diverse set of HIV-1 strains from different clades 868:919 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 42 from clades 914:919 arg1 strains 891:897 HIV-1 strains 885:897 HIV-1 strains from different clades 885:919 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 1 43 theme animal 250:255 arg1 models 257:262 animal models 250:262 animal models 250:262 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 6 44 theme lineage 1065:1071 arg1 result 1008:1013 the result 1004:1013 the result of a polyclonal mixture rather than a single bNAb lineage 1004:1071 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 44 theme lineage 1065:1071 arg1 potency 980:986 potency 980:986 potency 980:986 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 44 theme lineage 1065:1071 arg1 breadth 968:974 the patient's remarkable serum breadth 937:974 the patient's remarkable serum breadth 937:974 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 4 45 theme time 576:579 arg1 points 581:586 various time points 568:586 various time points post infection 568:601 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 6 46 from set 878:880 arg1 clades 914:919 different clades 904:919 different clades 904:919 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 7 47 theme microscopy 1104:1113 arg1 structures 1115:1124 High-resolution cryo-electron microscopy structures 1074:1124 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual 1074:1221 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 6 48 theme HIV-1 885:889 arg1 strains 891:897 HIV-1 strains 885:897 HIV-1 strains from different clades 885:919 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 7 49 theme High-resolution 1074:1088 arg1 microscopy 1104:1113 High-resolution cryo-electron microscopy 1074:1113 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual 1074:1221 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 9 50 theme vaccine 1634:1640 arg1 induction 1565:1573 the induction 1561:1573 the induction of combinations of moderately broad NAbs 1561:1614 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 9 50 theme vaccine 1634:1640 arg1 strategy 1642:1649 a viable vaccine strategy 1625:1649 a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses 1625:1710 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 7 51 theme trimer 1394:1399 arg1 binding 1332:1338 binding 1332:1338 binding to HIV-1 Env N-linked glycans 1332:1368 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 7 51 theme trimer 1394:1399 arg1 disassembly 1375:1385 disassembly 1375:1385 disassembly of the trimer 1375:1399 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 7 51 theme trimer 1394:1399 arg1 site 1326:1329 the receptor binding site 1305:1329 the receptor binding site 1305:1329 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 7 51 theme trimer 1394:1399 arg1 trimer 1394:1399 the trimer 1390:1399 the trimer 1390:1399 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 4 52 theme monoclonal 654:663 arg1 antibodies 665:674 monoclonal antibodies 654:674 monoclonal antibodies (mAbs) 654:681 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 4 52 theme monoclonal 654:663 arg1 mAbs 677:680 mAbs 677:680 mAbs 677:680 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 1 53 theme HIV-1 192:196 arg1 subtypes 198:205 most HIV-1 subtypes 187:205 most HIV-1 subtypes 187:205 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 5 54 theme V3 831:832 arg1 interface 786:794 the gp120-gp41 interface 771:794 the gp120-gp41 interface 771:794 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 5 54 theme V3 831:832 arg1 region 834:839 V3 region 831:839 V3 region 831:839 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 5 54 theme V3 831:832 arg1 epitopes 744:751 distinct epitopes 735:751 distinct epitopes 735:751 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 6 55 theme remarkable 951:960 arg1 result 1008:1013 the result 1004:1013 the result of a polyclonal mixture rather than a single bNAb lineage 1004:1071 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 55 theme remarkable 951:960 arg1 potency 980:986 potency 980:986 potency 980:986 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 6 55 theme remarkable 951:960 arg1 breadth 968:974 the patient's remarkable serum breadth 937:974 the patient's remarkable serum breadth 937:974 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 4 56 theme elite 626:630 arg1 neutralizer 632:642 an HIV-1 infected elite neutralizer 608:642 an HIV-1 infected elite neutralizer 608:642 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 9 57 theme wide 1672:1675 arg1 range 1677:1681 a wide range 1670:1681 a wide range of circulating HIV-1 viruses 1670:1710 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 8 58 theme diverse 1426:1432 arg1 NAbs 1434:1437 diverse NAbs 1426:1437 diverse NAbs 1426:1437 These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. 36395347 1 59 from infection 237:245 arg1 models 257:262 animal models 250:262 animal models 250:262 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 5 60 from epitopes 744:751 arg1 Env 756:758 Env 756:758 Env 756:758 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 7 61 theme Env 1349:1351 arg1 glycans 1362:1368 HIV-1 Env N-linked glycans 1343:1368 HIV-1 Env N-linked glycans 1343:1368 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 5 62 theme Multiple 684:691 arg1 lineages 702:709 Multiple antibody lineages 684:709 Multiple antibody lineages 684:709 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 9 63 theme HIV-1 1698:1702 arg1 viruses 1704:1710 circulating HIV-1 viruses 1686:1710 circulating HIV-1 viruses 1686:1710 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 7 64 theme same 1207:1210 arg1 individual 1212:1221 the same individual 1203:1221 the same individual 1203:1221 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 1 65 theme remarkable 148:157 arg1 breadth 159:165 remarkable breadth 148:165 remarkable breadth 148:165 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 5 66 theme distinct 735:742 arg1 interface 786:794 the gp120-gp41 interface 771:794 the gp120-gp41 interface 771:794 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 5 66 theme distinct 735:742 arg1 site 809:812 CD4-binding site 797:812 CD4-binding site 797:812 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 5 66 theme distinct 735:742 arg1 face 822:825 silent face 815:825 silent face 815:825 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 5 66 theme distinct 735:742 arg1 epitopes 744:751 distinct epitopes 735:751 distinct epitopes 735:751 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 5 66 theme distinct 735:742 arg1 region 834:839 V3 region 831:839 V3 region 831:839 Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. 36395347 7 67 theme receptor 1309:1316 arg1 trimer 1394:1399 the trimer 1390:1399 the trimer 1390:1399 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 7 67 theme receptor 1309:1316 arg1 site 1326:1329 the receptor binding site 1305:1329 the receptor binding site 1305:1329 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 3 68 theme neutralization 374:387 arg1 breadth 389:395 neutralization breadth 374:395 neutralization breadth 374:395 Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. 36395347 6 69 theme bNAb 1060:1063 arg1 lineage 1065:1071 a single bNAb lineage 1051:1071 a polyclonal mixture rather than a single bNAb lineage 1018:1071 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 4 70 theme envelope 500:507 arg1 Env 524:526 Env 524:526 Env 524:526 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 4 70 theme envelope 500:507 arg1 glycoproteins 509:521 HIV-1 envelope glycoproteins 494:521 HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells 494:549 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 3 71 theme bNAb 457:460 arg1 responses 462:470 protective bNAb responses 446:470 protective bNAb responses 446:470 Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. 36395347 0 72 theme antibody 14:21 arg1 lineages 23:30 Complementary antibody lineages 0:30 Complementary antibody lineages 0:30 Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer. 36395347 1 73 theme neutralizing 111:122 arg1 bNAbs 136:140 bNAbs 136:140 bNAbs 136:140 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 1 73 theme neutralizing 111:122 arg1 antibodies 124:133 Broadly neutralizing antibodies 103:133 Broadly neutralizing antibodies (bNAbs) 103:141 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 8 74 theme HIV-1 1526:1530 arg1 individuals 1541:1551 HIV-1 infected individuals 1526:1551 HIV-1 infected individuals 1526:1551 These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. 36395347 6 75 theme polyclonal 1020:1029 arg1 mixture 1031:1037 a polyclonal mixture 1018:1037 a polyclonal mixture rather than a single bNAb lineage 1018:1071 The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. 36395347 3 76 theme strategies 425:434 arg1 design 415:420 the design 411:420 the design of strategies to elicit protective bNAb responses by vaccination 411:485 Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. 36395347 4 77 theme IgG+ 538:541 arg1 cells 545:549 -specific IgG+ B cells 528:549 HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells 494:549 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 7 78 used used 1246:1249 arg2 NAbs 1241:1244 the NAbs 1237:1244 the NAbs 1237:1244 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 7 79 theme neutralizing 1133:1144 arg1 NAbs 1152:1155 NAbs 1152:1155 NAbs 1152:1155 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 7 79 theme neutralizing 1133:1144 arg1 mAbs 1146:1149 the neutralizing mAbs 1129:1149 the neutralizing mAbs (NAbs) 1129:1156 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 8 80 theme neutralizing 1495:1506 arg1 response 1514:1521 a broad and potent neutralizing serum response 1476:1521 a broad and potent neutralizing serum response in HIV-1 infected individuals 1476:1551 These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. 36395347 4 81 dep glycoproteins 509:521 arg1 cells 545:549 -specific IgG+ B cells 528:549 HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells 494:549 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 9 82 theme combinations 1578:1589 arg1 induction 1565:1573 the induction 1561:1573 the induction of combinations of moderately broad NAbs 1561:1614 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 9 82 theme combinations 1578:1589 arg1 strategy 1642:1649 a viable vaccine strategy 1625:1649 a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses 1625:1710 Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. 36395347 1 83 theme HIV-1 231:235 arg1 infection 237:245 HIV-1 infection 231:245 HIV-1 infection in animal models 231:262 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 4 84 theme -specific 528:536 arg1 cells 545:549 -specific IgG+ B cells 528:549 HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells 494:549 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 7 85 theme binding 1318:1324 arg1 trimer 1394:1399 the trimer 1390:1399 the trimer 1390:1399 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 7 85 theme binding 1318:1324 arg1 site 1326:1329 the receptor binding site 1305:1329 the receptor binding site 1305:1329 High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. 36395347 4 86 theme infected 617:624 arg1 neutralizer 632:642 an HIV-1 infected elite neutralizer 608:642 an HIV-1 infected elite neutralizer 608:642 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36395347 1 87 contain have 143:146 arg2 potency 171:177 potency 171:177 potency 171:177 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 1 87 contain have 143:146 arg2 breadth 159:165 remarkable breadth 148:165 remarkable breadth 148:165 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 1 87 contain have 143:146 arg1 bNAbs 136:140 bNAbs 136:140 bNAbs 136:140 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 1 87 contain have 143:146 arg1 antibodies 124:133 Broadly neutralizing antibodies 103:133 Broadly neutralizing antibodies (bNAbs) 103:141 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. 36395347 4 88 theme HIV-1 611:615 arg1 neutralizer 632:642 an HIV-1 infected elite neutralizer 608:642 an HIV-1 infected elite neutralizer 608:642 Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). 36066083 2 0 theme DNA 631:633 arg1 adducts 635:641 mutation-inducing DNA adducts 613:641 mutation-inducing DNA adducts in the colorectum 613:659 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 6 1 theme paraffin-embedded 1354:1370 arg1 tissues 1379:1385 fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues 1322:1385 fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues 1322:1385 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 7 2 theme AP 1566:1567 arg1 sites 1570:1574 apurinic/apyrimidinic (AP) sites 1543:1574 apurinic/apyrimidinic (AP) sites 1543:1574 Some NOCs form O6-carboxymethyl-2'-deoxyguanosine, O6-methyl-2'-deoxyguanosine, and unstable quaternary N-linked purine/pyrimidine adducts, which generate apurinic/apyrimidinic (AP) sites. 36066083 3 3 theme NOC 738:740 arg1 formation 742:750 endogenous NOC formation 727:750 endogenous NOC formation 727:750 Heme iron in red meat may contribute to oxidative DNA damage and endogenous NOC formation. 36066083 13 4 theme 6-oxo-M1dG 2264:2273 arg1 levels 2282:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. 36066083 7 5 theme apurinic/apyrimidinic 1543:1563 arg1 sites 1570:1574 apurinic/apyrimidinic (AP) sites 1543:1574 apurinic/apyrimidinic (AP) sites 1543:1574 Some NOCs form O6-carboxymethyl-2'-deoxyguanosine, O6-methyl-2'-deoxyguanosine, and unstable quaternary N-linked purine/pyrimidine adducts, which generate apurinic/apyrimidinic (AP) sites. 36066083 1 6 theme mechanistic 208:218 arg1 studies 220:226 Epidemiological and mechanistic studies 188:226 Epidemiological and mechanistic studies 188:226 Epidemiological and mechanistic studies suggest that processed and red meat consumption and tobacco smoking are associated with colorectal cancer (CRC) risk. 36066083 6 7 theme carcinogen-treated 1288:1305 arg1 rats 1307:1310 carcinogen-treated rats 1288:1310 carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues 1288:1385 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 2 8 from compounds 398:406 arg1 HAAs 468:471 HAAs 468:471 HAAs 468:471 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 8 from compounds 398:406 arg1 amines 460:465 heterocyclic aromatic amines 438:465 heterocyclic aromatic amines (HAAs) 438:472 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 8 from compounds 398:406 arg1 meats 428:432 processed meats 418:432 processed meats 418:432 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 6 9 theme tobacco-associated 1190:1207 arg1 carcinogens 1209:1219 tobacco-associated carcinogens 1190:1219 tobacco-associated carcinogens 1190:1219 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 10 10 theme DNA 1910:1912 arg1 μg 1904:1905 3 μg 1902:1905 3 μg of DNA 1902:1912 Limits of quantitation ranged from 0.1 to 1.1 adducts per 108 bases using 3 μg of DNA. 36066083 1 11 theme processed 241:249 arg1 consumption 264:274 processed and red meat consumption 241:274 processed and red meat consumption 241:274 Epidemiological and mechanistic studies suggest that processed and red meat consumption and tobacco smoking are associated with colorectal cancer (CRC) risk. 36066083 7 12 theme N-linked 1492:1499 arg1 adducts 1519:1525 unstable quaternary N-linked purine/pyrimidine adducts 1472:1525 unstable quaternary N-linked purine/pyrimidine adducts 1472:1525 Some NOCs form O6-carboxymethyl-2'-deoxyguanosine, O6-methyl-2'-deoxyguanosine, and unstable quaternary N-linked purine/pyrimidine adducts, which generate apurinic/apyrimidinic (AP) sites. 36066083 0 13 theme Biomonitoring 151:163 arg1 Damage 180:185 Biomonitoring Colorectal DNA Damage 151:185 Biomonitoring Colorectal DNA Damage 151:185 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 13 14 theme -one 2248:2251 arg1 levels 2282:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. 36066083 1 15 theme red 255:257 arg1 consumption 264:274 processed and red meat consumption 241:274 processed and red meat consumption 241:274 Epidemiological and mechanistic studies suggest that processed and red meat consumption and tobacco smoking are associated with colorectal cancer (CRC) risk. 36066083 8 16 theme AP 1577:1578 arg1 sites 1580:1584 AP sites 1577:1584 AP sites 1577:1584 AP sites were quantitated following derivatization with O-(pyridin-3-yl-methyl)hydroxylamine. 36066083 7 17 theme unstable 1472:1479 arg1 adducts 1519:1525 unstable quaternary N-linked purine/pyrimidine adducts 1472:1525 unstable quaternary N-linked purine/pyrimidine adducts 1472:1525 Some NOCs form O6-carboxymethyl-2'-deoxyguanosine, O6-methyl-2'-deoxyguanosine, and unstable quaternary N-linked purine/pyrimidine adducts, which generate apurinic/apyrimidinic (AP) sites. 36066083 0 18 theme DNA 176:178 arg1 Damage 180:185 Biomonitoring Colorectal DNA Damage 151:185 Biomonitoring Colorectal DNA Damage 151:185 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 2 19 theme reactive 576:583 arg1 intermediates 585:597 reactive intermediates 576:597 reactive intermediates that may form mutation-inducing DNA adducts in the colorectum 576:659 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 6 20 theme chromatography/high-resolution 1051:1080 arg1 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 20 theme chromatography/high-resolution 1051:1080 arg1 spectrometry 1117:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry 1032:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods 1032:1148 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 11 21 theme fresh-frozen 2019:2030 arg1 specimens 2041:2049 fresh-frozen and FFPE specimens 2019:2049 fresh-frozen and FFPE specimens for most adducts 2019:2066 Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. 36066083 6 22 theme robust 1032:1037 arg1 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 22 theme robust 1032:1037 arg1 spectrometry 1117:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry 1032:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods 1032:1148 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 2 23 from amines 460:465 arg1 meats 529:533 grilled meats 521:533 grilled meats 521:533 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 23 from amines 460:465 arg1 smoke 547:551 tobacco smoke 539:551 tobacco smoke 539:551 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 14 24 theme DNA 2423:2425 arg1 adducts 2427:2433 DNA adducts 2423:2433 DNA adducts 2423:2433 Human biomonitoring studies can implement LC/HRAMS2 assays for DNA adducts and AP sites outlined in this work to advance our understanding of CRC etiology. 36066083 11 25 theme Adduct 1915:1920 arg1 formation 1922:1930 Adduct formation 1915:1930 Adduct formation in animals 1915:1941 Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. 36066083 0 26 theme Chromatography/High-Resolution 69:98 arg1 Spectrometry 121:132 Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry 57:132 Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry 57:132 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 1 27 theme Epidemiological 188:202 arg1 studies 220:226 Epidemiological and mechanistic studies 188:226 Epidemiological and mechanistic studies 188:226 Epidemiological and mechanistic studies suggest that processed and red meat consumption and tobacco smoking are associated with colorectal cancer (CRC) risk. 36066083 2 28 theme tobacco 539:545 arg1 smoke 547:551 tobacco smoke 539:551 tobacco smoke 539:551 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 0 29 theme Tandem 109:114 arg1 Spectrometry 121:132 Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry 57:132 Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry 57:132 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 10 30 theme quantitation 1838:1849 arg1 Limits 1828:1833 Limits 1828:1833 Limits of quantitation 1828:1849 Limits of quantitation ranged from 0.1 to 1.1 adducts per 108 bases using 3 μg of DNA. 36066083 4 31 theme colorectal 788:797 arg1 damage 803:808 colorectal DNA damage 788:808 colorectal DNA damage 788:808 However, the chemicals involved in colorectal DNA damage and the paradigms of CRC etiology remain unproven. 36066083 13 32 link peroxide-derived 2166:2181 arg1 levels 2282:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. 36066083 2 33 theme processed 418:426 arg1 meats 428:432 processed meats 418:432 processed meats 418:432 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 13 34 theme lipid 2160:2164 arg1 levels 2282:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. 36066083 5 35 theme human 999:1003 arg1 colorectum 1005:1014 the human colorectum 995:1014 the human colorectum 995:1014 There is a critical need to establish physicochemical methods for identifying and quantitating DNA damage induced by genotoxicants in the human colorectum. 36066083 6 36 from products 1244:1251 arg1 colon 1267:1271 colon 1267:1271 colon 1267:1271 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 36 from products 1244:1251 arg1 rectum 1278:1283 rectum 1278:1283 rectum 1278:1283 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 36 from products 1244:1251 arg1 liver 1260:1264 the liver 1256:1264 the liver 1256:1264 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 0 37 theme Multi-DNA 0:8 arg1 Adduct 10:15 Multi-DNA Adduct 0:15 Multi-DNA Adduct 0:15 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 1 38 theme colorectal 316:325 arg1 CRC 335:337 CRC 335:337 CRC 335:337 Epidemiological and mechanistic studies suggest that processed and red meat consumption and tobacco smoking are associated with colorectal cancer (CRC) risk. 36066083 1 38 theme colorectal 316:325 arg1 cancer 327:332 colorectal cancer 316:332 colorectal cancer (CRC) risk 316:343 Epidemiological and mechanistic studies suggest that processed and red meat consumption and tobacco smoking are associated with colorectal cancer (CRC) risk. 36066083 9 39 theme stable 1714:1719 arg1 standards 1746:1754 stable isotope-labeled internal standards 1714:1754 stable isotope-labeled internal standards 1714:1754 DNA adduct quantitation was conducted with stable isotope-labeled internal standards, and method performance was validated for accuracy and reproducibility. 36066083 6 40 theme spectrometry 1117:1128 arg1 methods 1142:1148 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods 1032:1148 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods 1032:1148 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 12 41 dep colorectum 2113:2122 arg1 the 2109:2111 the 2109:2111 the 2109:2111 AP sites increased by 25- to 75-fold in the colorectum and liver, respectively. 36066083 10 42 dep 1.1 1870:1872 arg1 to 1867:1868 to 1867:1868 to 1867:1868 Limits of quantitation ranged from 0.1 to 1.1 adducts per 108 bases using 3 μg of DNA. 36066083 14 43 theme Human 2360:2364 arg1 studies 2380:2386 Human biomonitoring studies 2360:2386 Human biomonitoring studies 2360:2386 Human biomonitoring studies can implement LC/HRAMS2 assays for DNA adducts and AP sites outlined in this work to advance our understanding of CRC etiology. 36066083 2 44 theme aromatic 451:458 arg1 HAAs 468:471 HAAs 468:471 HAAs 468:471 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 44 theme aromatic 451:458 arg1 amines 460:465 heterocyclic aromatic amines 438:465 heterocyclic aromatic amines (HAAs) 438:472 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 6 45 theme peroxidation 1231:1242 arg1 products 1244:1251 lipid peroxidation products 1225:1251 lipid peroxidation products 1225:1251 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 9 46 theme internal 1737:1744 arg1 standards 1746:1754 stable isotope-labeled internal standards 1714:1754 stable isotope-labeled internal standards 1714:1754 DNA adduct quantitation was conducted with stable isotope-labeled internal standards, and method performance was validated for accuracy and reproducibility. 36066083 6 47 theme tandem 1105:1110 arg1 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 47 theme tandem 1105:1110 arg1 spectrometry 1117:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry 1032:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods 1032:1148 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 48 from carcinogens 1209:1219 arg1 colon 1267:1271 colon 1267:1271 colon 1267:1271 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 48 from carcinogens 1209:1219 arg1 rectum 1278:1283 rectum 1278:1283 rectum 1278:1283 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 48 from carcinogens 1209:1219 arg1 liver 1260:1264 the liver 1256:1264 the liver 1256:1264 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 11 49 theme FFPE 2036:2039 arg1 specimens 2041:2049 fresh-frozen and FFPE specimens 2019:2049 fresh-frozen and FFPE specimens for most adducts 2019:2066 Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. 36066083 0 50 theme Site 28:31 arg1 Quantitation 33:44 Abasic Site Quantitation 21:44 Abasic Site Quantitation 21:44 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 0 51 dep In 46:47 arg1 Vivo 49:52 Vivo 49:52 Vivo 49:52 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 6 52 theme mass 1091:1094 arg1 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 52 theme mass 1091:1094 arg1 spectrometry 1117:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry 1032:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods 1032:1148 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 2 53 theme polycyclic 478:487 arg1 PAHs 512:515 PAHs 512:515 PAHs 512:515 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 53 theme polycyclic 478:487 arg1 hydrocarbons 498:509 polycyclic aromatic hydrocarbons 478:509 polycyclic aromatic hydrocarbons (PAHs) 478:516 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 54 from adducts 635:641 arg1 colorectum 650:659 the colorectum 646:659 the colorectum 646:659 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 3 55 theme Heme 662:665 arg1 iron 667:670 Heme iron 662:670 Heme iron in red meat 662:682 Heme iron in red meat may contribute to oxidative DNA damage and endogenous NOC formation. 36066083 4 56 theme etiology 835:842 arg1 paradigms 818:826 the paradigms 814:826 the paradigms of CRC etiology 814:842 However, the chemicals involved in colorectal DNA damage and the paradigms of CRC etiology remain unproven. 36066083 4 56 theme etiology 835:842 arg1 chemicals 766:774 the chemicals 762:774 the chemicals involved in colorectal DNA damage 762:808 However, the chemicals involved in colorectal DNA damage and the paradigms of CRC etiology remain unproven. 36066083 6 57 from adducts 1165:1171 arg1 colon 1267:1271 colon 1267:1271 colon 1267:1271 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 57 from adducts 1165:1171 arg1 rectum 1278:1283 rectum 1278:1283 rectum 1278:1283 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 57 from adducts 1165:1171 arg1 liver 1260:1264 the liver 1256:1264 the liver 1256:1264 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 0 58 theme In 46:47 arg1 Adduct 10:15 Multi-DNA Adduct 0:15 Multi-DNA Adduct 0:15 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 13 59 theme carcinogen 2311:2320 arg1 dosing 2322:2327 carcinogen dosing 2311:2327 carcinogen dosing 2311:2327 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. 36066083 9 60 theme method 1761:1766 arg1 performance 1768:1778 method performance 1761:1778 method performance 1761:1778 DNA adduct quantitation was conducted with stable isotope-labeled internal standards, and method performance was validated for accuracy and reproducibility. 36066083 1 61 theme meat 259:262 arg1 consumption 264:274 processed and red meat consumption 241:274 processed and red meat consumption 241:274 Epidemiological and mechanistic studies suggest that processed and red meat consumption and tobacco smoking are associated with colorectal cancer (CRC) risk. 36066083 8 62 with derivatization 1613:1626 arg1 hydroxylamine 1656:1668 O-(pyridin-3-yl-methyl)hydroxylamine 1633:1668 O-(pyridin-3-yl-methyl)hydroxylamine 1633:1668 AP sites were quantitated following derivatization with O-(pyridin-3-yl-methyl)hydroxylamine. 36066083 7 63 link N-linked 1492:1499 arg1 adducts 1519:1525 unstable quaternary N-linked purine/pyrimidine adducts 1472:1525 unstable quaternary N-linked purine/pyrimidine adducts 1472:1525 Some NOCs form O6-carboxymethyl-2'-deoxyguanosine, O6-methyl-2'-deoxyguanosine, and unstable quaternary N-linked purine/pyrimidine adducts, which generate apurinic/apyrimidinic (AP) sites. 36066083 14 64 theme CRC 2502:2504 arg1 etiology 2506:2513 CRC etiology 2502:2513 CRC etiology 2502:2513 Human biomonitoring studies can implement LC/HRAMS2 assays for DNA adducts and AP sites outlined in this work to advance our understanding of CRC etiology. 36066083 2 65 theme N-nitroso 388:396 arg1 NOCs 409:412 NOCs 409:412 NOCs 409:412 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 65 theme N-nitroso 388:396 arg1 compounds 398:406 N-nitroso compounds 388:406 N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke 388:551 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 66 theme mutation-inducing 613:629 arg1 adducts 635:641 mutation-inducing DNA adducts 613:641 mutation-inducing DNA adducts in the colorectum 613:659 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 3 67 theme oxidative 702:710 arg1 damage 716:721 oxidative DNA damage 702:721 oxidative DNA damage 702:721 Heme iron in red meat may contribute to oxidative DNA damage and endogenous NOC formation. 36066083 6 68 theme formalin-fixed 1339:1352 arg1 tissues 1379:1385 fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues 1322:1385 fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues 1322:1385 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 3 69 from iron 667:670 arg1 meat 679:682 red meat 675:682 red meat 675:682 Heme iron in red meat may contribute to oxidative DNA damage and endogenous NOC formation. 36066083 6 70 theme fresh-frozen 1322:1333 arg1 tissues 1379:1385 fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues 1322:1385 fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues 1322:1385 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 71 dep paraffin-embedded 1354:1370 arg1 FFPE 1373:1376 FFPE 1373:1376 FFPE 1373:1376 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 72 theme lipid 1225:1229 arg1 products 1244:1251 lipid peroxidation products 1225:1251 lipid peroxidation products 1225:1251 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 3 73 theme endogenous 727:736 arg1 formation 742:750 endogenous NOC formation 727:750 endogenous NOC formation 727:750 Heme iron in red meat may contribute to oxidative DNA damage and endogenous NOC formation. 36066083 6 74 theme rats 1307:1310 arg1 colon 1267:1271 colon 1267:1271 colon 1267:1271 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 74 theme rats 1307:1310 arg1 rectum 1278:1283 rectum 1278:1283 rectum 1278:1283 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 74 theme rats 1307:1310 arg1 liver 1260:1264 the liver 1256:1264 the liver 1256:1264 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 2 75 theme Several 346:352 arg1 classes 354:360 Several classes 346:360 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, 346:552 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 5 76 theme critical 872:879 arg1 need 881:884 a critical need 870:884 a critical need to establish physicochemical methods for identifying and quantitating DNA damage induced by genotoxicants in the human colorectum 870:1014 There is a critical need to establish physicochemical methods for identifying and quantitating DNA damage induced by genotoxicants in the human colorectum. 36066083 9 77 theme DNA 1671:1673 arg1 quantitation 1682:1693 DNA adduct quantitation 1671:1693 DNA adduct quantitation 1671:1693 DNA adduct quantitation was conducted with stable isotope-labeled internal standards, and method performance was validated for accuracy and reproducibility. 36066083 0 78 theme Colorectal 165:174 arg1 Damage 180:185 Biomonitoring Colorectal DNA Damage 151:185 Biomonitoring Colorectal DNA Damage 151:185 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 11 79 from formation 1922:1930 arg1 animals 1935:1941 animals 1935:1941 animals 1935:1941 Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. 36066083 7 80 theme purine/pyrimidine 1501:1517 arg1 adducts 1519:1525 unstable quaternary N-linked purine/pyrimidine adducts 1472:1525 unstable quaternary N-linked purine/pyrimidine adducts 1472:1525 Some NOCs form O6-carboxymethyl-2'-deoxyguanosine, O6-methyl-2'-deoxyguanosine, and unstable quaternary N-linked purine/pyrimidine adducts, which generate apurinic/apyrimidinic (AP) sites. 36066083 12 81 theme AP 2069:2070 arg1 sites 2072:2076 AP sites 2069:2076 AP sites 2069:2076 AP sites increased by 25- to 75-fold in the colorectum and liver, respectively. 36066083 7 82 theme quaternary 1481:1490 arg1 adducts 1519:1525 unstable quaternary N-linked purine/pyrimidine adducts 1472:1525 unstable quaternary N-linked purine/pyrimidine adducts 1472:1525 Some NOCs form O6-carboxymethyl-2'-deoxyguanosine, O6-methyl-2'-deoxyguanosine, and unstable quaternary N-linked purine/pyrimidine adducts, which generate apurinic/apyrimidinic (AP) sites. 36066083 6 83 theme accurate 1082:1089 arg1 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 83 theme accurate 1082:1089 arg1 spectrometry 1117:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry 1032:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods 1032:1148 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 11 84 dep ∼1 1968:1969 arg1 to 1965:1966 to 1965:1966 to 1965:1966 Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. 36066083 11 85 from levels 2009:2014 arg1 specimens 2041:2049 fresh-frozen and FFPE specimens 2019:2049 fresh-frozen and FFPE specimens for most adducts 2019:2066 Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. 36066083 14 86 theme AP 2439:2440 arg1 sites 2442:2446 AP sites 2439:2446 AP sites 2439:2446 Human biomonitoring studies can implement LC/HRAMS2 assays for DNA adducts and AP sites outlined in this work to advance our understanding of CRC etiology. 36066083 0 87 theme Nano-Liquid 57:67 arg1 Spectrometry 121:132 Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry 57:132 Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry 57:132 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 6 88 theme nano-liquid 1039:1049 arg1 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 88 theme nano-liquid 1039:1049 arg1 spectrometry 1117:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry 1032:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods 1032:1148 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 8 89 theme O- 1633:1634 arg1 hydroxylamine 1656:1668 O-(pyridin-3-yl-methyl)hydroxylamine 1633:1668 O-(pyridin-3-yl-methyl)hydroxylamine 1633:1668 AP sites were quantitated following derivatization with O-(pyridin-3-yl-methyl)hydroxylamine. 36066083 13 90 theme adduct 2275:2280 arg1 levels 2282:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. 36066083 0 91 theme Orbitrap 100:107 arg1 Spectrometry 121:132 Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry 57:132 Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry 57:132 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 5 92 theme physicochemical 899:913 arg1 methods 915:921 physicochemical methods 899:921 physicochemical methods for identifying and quantitating DNA damage induced by genotoxicants in the human colorectum 899:1014 There is a critical need to establish physicochemical methods for identifying and quantitating DNA damage induced by genotoxicants in the human colorectum. 36066083 8 93 theme pyridin-3-yl-methyl 1636:1654 arg1 hydroxylamine 1656:1668 O-(pyridin-3-yl-methyl)hydroxylamine 1633:1668 O-(pyridin-3-yl-methyl)hydroxylamine 1633:1668 AP sites were quantitated following derivatization with O-(pyridin-3-yl-methyl)hydroxylamine. 36066083 0 94 theme Mass 116:119 arg1 Spectrometry 121:132 Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry 57:132 Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry 57:132 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 9 95 theme adduct 1675:1680 arg1 quantitation 1682:1693 DNA adduct quantitation 1671:1693 DNA adduct quantitation 1671:1693 DNA adduct quantitation was conducted with stable isotope-labeled internal standards, and method performance was validated for accuracy and reproducibility. 36066083 14 96 theme LC/HRAMS2 2402:2410 arg1 assays 2412:2417 LC/HRAMS2 assays 2402:2417 LC/HRAMS2 assays for DNA adducts and AP sites outlined in this work to advance our understanding of CRC etiology 2402:2513 Human biomonitoring studies can implement LC/HRAMS2 assays for DNA adducts and AP sites outlined in this work to advance our understanding of CRC etiology. 36066083 13 97 theme Endogenous 2149:2158 arg1 levels 2282:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. 36066083 2 98 theme grilled 521:527 arg1 meats 529:533 grilled meats 521:533 grilled meats 521:533 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 99 from hydrocarbons 498:509 arg1 meats 529:533 grilled meats 521:533 grilled meats 521:533 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 99 from hydrocarbons 498:509 arg1 smoke 547:551 tobacco smoke 539:551 tobacco smoke 539:551 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 12 100 dep 25- 2091:2093 arg1 to 2095:2096 to 2095:2096 to 2095:2096 AP sites increased by 25- to 75-fold in the colorectum and liver, respectively. 36066083 11 101 from ∼1 1968:1969 arg1 bases 1978:1982 105 bases 1974:1982 105 bases 1974:1982 Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. 36066083 13 102 theme peroxide-derived 2166:2181 arg1 levels 2282:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels 2149:2287 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. 36066083 5 103 theme DNA 956:958 arg1 damage 960:965 DNA damage 956:965 DNA damage induced by genotoxicants in the human colorectum 956:1014 There is a critical need to establish physicochemical methods for identifying and quantitating DNA damage induced by genotoxicants in the human colorectum. 36066083 14 104 theme biomonitoring 2366:2378 arg1 studies 2380:2386 Human biomonitoring studies 2360:2386 Human biomonitoring studies 2360:2386 Human biomonitoring studies can implement LC/HRAMS2 assays for DNA adducts and AP sites outlined in this work to advance our understanding of CRC etiology. 36066083 0 105 theme Abasic 21:26 arg1 Quantitation 33:44 Abasic Site Quantitation 21:44 Abasic Site Quantitation 21:44 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 1 106 theme cancer 327:332 arg1 risk 340:343 colorectal cancer (CRC) risk 316:343 colorectal cancer (CRC) risk 316:343 Epidemiological and mechanistic studies suggest that processed and red meat consumption and tobacco smoking are associated with colorectal cancer (CRC) risk. 36066083 9 107 theme isotope-labeled 1721:1735 arg1 standards 1746:1754 stable isotope-labeled internal standards 1714:1754 stable isotope-labeled internal standards 1714:1754 DNA adduct quantitation was conducted with stable isotope-labeled internal standards, and method performance was validated for accuracy and reproducibility. 36066083 6 108 theme mass 1112:1115 arg1 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 108 theme mass 1112:1115 arg1 spectrometry 1117:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry 1032:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods 1032:1148 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 2 109 theme heterocyclic 438:449 arg1 HAAs 468:471 HAAs 468:471 HAAs 468:471 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 109 theme heterocyclic 438:449 arg1 amines 460:465 heterocyclic aromatic amines 438:465 heterocyclic aromatic amines (HAAs) 438:472 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 13 110 theme FFPE 2346:2349 arg1 tissues 2351:2357 FFPE tissues 2346:2357 FFPE tissues 2346:2357 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. 36066083 12 111 from 25- 2091:2093 arg1 liver 2128:2132 liver 2128:2132 liver 2128:2132 AP sites increased by 25- to 75-fold in the colorectum and liver, respectively. 36066083 12 111 from 25- 2091:2093 arg1 colorectum 2113:2122 colorectum 2113:2122 colorectum 2113:2122 AP sites increased by 25- to 75-fold in the colorectum and liver, respectively. 36066083 6 112 theme Orbitrap 1096:1103 arg1 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 LC/HRAMS2 1131:1139 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 112 theme Orbitrap 1096:1103 arg1 spectrometry 1117:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry 1032:1128 robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods 1032:1148 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 2 113 theme aromatic 489:496 arg1 PAHs 512:515 PAHs 512:515 PAHs 512:515 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 113 theme aromatic 489:496 arg1 hydrocarbons 498:509 polycyclic aromatic hydrocarbons 478:509 polycyclic aromatic hydrocarbons (PAHs) 478:516 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 11 114 theme most 2055:2058 arg1 adducts 2060:2066 most adducts 2055:2066 most adducts 2055:2066 Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. 36066083 6 115 theme meat 1181:1184 arg1 carcinogens 1209:1219 tobacco-associated carcinogens 1190:1219 tobacco-associated carcinogens 1190:1219 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 115 theme meat 1181:1184 arg1 products 1244:1251 lipid peroxidation products 1225:1251 lipid peroxidation products 1225:1251 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 6 115 theme meat 1181:1184 arg1 adducts 1165:1171 DNA adducts 1161:1171 DNA adducts of nine meat 1161:1184 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 4 116 theme CRC 831:833 arg1 etiology 835:842 CRC etiology 831:842 CRC etiology 831:842 However, the chemicals involved in colorectal DNA damage and the paradigms of CRC etiology remain unproven. 36066083 2 117 theme carcinogens 365:375 arg1 classes 354:360 Several classes 346:360 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, 346:552 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 13 118 dep -one 2248:2251 arg1 M1dG 2254:2257 M1dG 2254:2257 M1dG 2254:2257 Endogenous lipid peroxide-derived 3-(2-deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and 6-oxo-M1dG adduct levels were not increased by carcinogen dosing but increased in FFPE tissues. 36066083 11 119 dep bases 1978:1982 arg1 occurring 1985:1993 occurring 1985:1993 occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts 1985:2066 Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. 36066083 3 120 theme red 675:677 arg1 meat 679:682 red meat 675:682 red meat 675:682 Heme iron in red meat may contribute to oxidative DNA damage and endogenous NOC formation. 36066083 4 121 theme DNA 799:801 arg1 damage 803:808 colorectal DNA damage 788:808 colorectal DNA damage 788:808 However, the chemicals involved in colorectal DNA damage and the paradigms of CRC etiology remain unproven. 36066083 0 122 dep Adduct 10:15 arg1 Methodology 135:145 Methodology 135:145 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 0:186 Multi-DNA Adduct and Abasic Site Quantitation In Vivo by Nano-Liquid Chromatography/High-Resolution Orbitrap Tandem Mass Spectrometry: Methodology for Biomonitoring Colorectal DNA Damage. 36066083 2 123 from meats 428:432 arg1 meats 529:533 grilled meats 521:533 grilled meats 521:533 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 2 123 from meats 428:432 arg1 smoke 547:551 tobacco smoke 539:551 tobacco smoke 539:551 Several classes of carcinogens, including N-nitroso compounds (NOCs) in processed meats and heterocyclic aromatic amines (HAAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled meats and tobacco smoke, undergo metabolism to reactive intermediates that may form mutation-inducing DNA adducts in the colorectum. 36066083 6 124 theme DNA 1161:1163 arg1 adducts 1165:1171 DNA adducts 1161:1171 DNA adducts of nine meat 1161:1184 We established robust nano-liquid chromatography/high-resolution accurate mass Orbitrap tandem mass spectrometry (LC/HRAMS2) methods to measure DNA adducts of nine meat and tobacco-associated carcinogens and lipid peroxidation products in the liver, colon, and rectum of carcinogen-treated rats employing fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues. 36066083 3 125 theme DNA 712:714 arg1 damage 716:721 oxidative DNA damage 702:721 oxidative DNA damage 702:721 Heme iron in red meat may contribute to oxidative DNA damage and endogenous NOC formation. 36066083 14 126 theme etiology 2506:2513 arg1 understanding 2485:2497 our understanding 2481:2497 our understanding of CRC etiology 2481:2513 Human biomonitoring studies can implement LC/HRAMS2 assays for DNA adducts and AP sites outlined in this work to advance our understanding of CRC etiology. 36066083 11 127 theme comparable 1998:2007 arg1 levels 2009:2014 comparable levels 1998:2014 comparable levels in fresh-frozen and FFPE specimens for most adducts 1998:2066 Adduct formation in animals ranged from ∼1 in 108 to ∼1 in 105 bases, occurring at comparable levels in fresh-frozen and FFPE specimens for most adducts. 36066083 1 128 theme tobacco 280:286 arg1 smoking 288:294 tobacco smoking 280:294 tobacco smoking 280:294 Epidemiological and mechanistic studies suggest that processed and red meat consumption and tobacco smoking are associated with colorectal cancer (CRC) risk. 35233578 9 0 theme targets 1376:1382 arg1 catalog 1343:1349 a catalog 1341:1349 a catalog of potential therapeutic targets 1341:1382 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35233578 5 1 theme SARS-CoV-2 673:682 arg1 proteins 684:691 SARS-CoV-2 proteins 673:691 SARS-CoV-2 proteins expressed in human lung epithelial cells 673:732 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35233578 4 2 theme separate 606:613 arg1 roles 615:619 their shared and separate roles 589:619 their shared and separate roles in replication, transcription, and viral packaging 589:670 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 3 3 theme SARS-CoV-2 349:358 arg1 interactions 368:379 SARS-CoV-2 protein interactions 349:379 SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells 349:438 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35233578 4 4 theme RNA 548:550 arg1 genome 558:563 the RNA viral genome 544:563 the RNA viral genome 544:563 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 7 5 theme different 1134:1142 arg1 variants 1155:1162 different SARS-CoV-2 variants 1134:1162 different SARS-CoV-2 variants 1134:1162 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 7 6 theme host 1114:1117 arg1 targets 1119:1125 potential antiviral host targets 1094:1125 potential antiviral host targets across different SARS-CoV-2 variants 1094:1162 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 9 7 theme viral 1302:1306 arg1 interactome 1320:1330 Our viral protein-RNA interactome 1298:1330 Our viral protein-RNA interactome 1298:1330 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35233578 5 8 theme host 754:757 arg1 RNAs 766:769 4773 unique host coding RNAs 742:769 4773 unique host coding RNAs 742:769 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35233578 6 9 theme ER 943:944 arg1 processing 946:955 ER processing 943:955 ER processing 943:955 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 7 10 theme host 1018:1021 arg1 genes 1023:1027 host genes 1018:1027 host genes targeted by viral proteins in human lung organoid cells 1018:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 3 11 theme host 396:399 arg1 RNAs 401:404 viral and host RNAs 386:404 viral and host RNAs 386:404 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35233578 9 12 dep a 1436:1436 arg1 safeguard 1438:1446 safeguard 1438:1446 safeguard against future pandemics 1438:1471 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35233578 4 13 from regions 533:539 arg1 genome 558:563 the RNA viral genome 544:563 the RNA viral genome 544:563 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 7 14 theme siRNA 999:1003 arg1 knockdown 1005:1013 siRNA knockdown 999:1013 siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells 999:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 8 15 theme cytokine 1248:1255 arg1 productions 1257:1267 cytokine productions 1248:1267 cytokine productions 1248:1267 Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. 35233578 8 15 theme cytokine 1248:1255 arg1 interleukin-1α/β 1280:1295 interleukin-1α/β 1280:1295 interleukin-1α/β 1280:1295 Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. 35233578 4 16 theme distinct 500:507 arg1 preferences 509:519 distinct preferences 500:519 distinct preferences 500:519 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 4 17 theme SARS-CoV-2 441:450 arg1 NSP12 468:472 NSP12 468:472 NSP12 468:472 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 4 17 theme SARS-CoV-2 441:450 arg1 nucleocapsid 479:490 nucleocapsid 479:490 nucleocapsid 479:490 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 4 17 theme SARS-CoV-2 441:450 arg1 NSP8 462:465 NSP8 462:465 NSP8 462:465 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 4 17 theme SARS-CoV-2 441:450 arg1 proteins 452:459 SARS-CoV-2 proteins 441:459 SARS-CoV-2 proteins 441:459 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 1 18 theme COVID-19 83:90 arg1 pandemic 92:99 The COVID-19 pandemic 79:99 The COVID-19 pandemic 79:99 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35233578 3 19 theme viral 386:390 arg1 RNAs 401:404 viral and host RNAs 386:404 viral and host RNAs 386:404 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35233578 4 20 theme specific 524:531 arg1 regions 533:539 specific regions 524:539 specific regions in the RNA viral genome 524:563 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 9 21 theme potential 1354:1362 arg1 targets 1376:1382 potential therapeutic targets 1354:1382 potential therapeutic targets 1354:1382 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35233578 2 22 contain has 195:197 arg1 betacoronvirus 180:193 The betacoronvirus 176:193 The betacoronvirus 176:193 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35233578 2 22 contain has 195:197 arg2 genome 220:225 a positive sense RNA genome 199:225 a positive sense RNA genome which encodes for several RNA binding proteins 199:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35233578 3 23 theme authentic 409:417 arg1 cells 434:438 authentic virus-infected cells 409:438 authentic virus-infected cells 409:438 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35233578 7 24 from proteins 1047:1054 arg1 cells 1079:1083 human lung organoid cells 1059:1083 human lung organoid cells 1059:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 7 25 theme potential 1094:1102 arg1 targets 1119:1125 potential antiviral host targets 1094:1125 potential antiviral host targets across different SARS-CoV-2 variants 1094:1162 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 8 26 theme gene 1196:1199 arg1 expression 1201:1210 host gene expression 1191:1210 host gene expression 1191:1210 Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. 35233578 6 27 theme N-linked 920:927 arg1 glycosylation 929:941 protein N-linked glycosylation ER processing and mitochondrial processes 912:983 glycosylation 929:941 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 3 28 theme virus-infected 419:432 arg1 cells 434:438 authentic virus-infected cells 409:438 authentic virus-infected cells 409:438 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35233578 3 29 from interactions 368:379 arg1 cells 434:438 authentic virus-infected cells 409:438 authentic virus-infected cells 409:438 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35233578 6 30 theme gene 815:818 arg1 expression 820:829 target gene expression 808:829 target gene expression 808:829 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 6 31 from pathways 900:907 arg1 processes 975:983 mitochondrial processes 961:983 mitochondrial processes 961:983 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 6 31 from pathways 900:907 arg1 glycosylation 929:941 protein N-linked glycosylation ER processing and mitochondrial processes 912:983 glycosylation 929:941 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 9 32 theme COVID-19 1424:1431 arg1 etiology 1412:1419 the etiology 1408:1419 the etiology of COVID-19 1408:1431 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35233578 6 33 theme target 808:813 arg1 expression 820:829 target gene expression 808:829 target gene expression 808:829 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 4 34 theme viral 656:660 arg1 packaging 662:670 viral packaging 656:670 viral packaging 656:670 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 0 35 theme functional 14:23 arg1 interrogation 25:37 functional interrogation 14:37 functional interrogation 14:37 Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. 35233578 4 36 theme shared 595:600 arg1 roles 615:619 their shared and separate roles 589:619 their shared and separate roles in replication, transcription, and viral packaging 589:670 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 3 37 theme enhanced 288:295 arg1 crosslinking 297:308 crosslinking 297:308 crosslinking 297:308 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35233578 2 38 theme positive 201:208 arg1 genome 220:225 a positive sense RNA genome 199:225 a positive sense RNA genome which encodes for several RNA binding proteins 199:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35233578 1 39 theme severe 114:119 arg1 syndrome-coronavirus-2 139:160 severe acute respiratory syndrome-coronavirus-2 114:160 severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) 114:173 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35233578 1 39 theme severe 114:119 arg1 SARS-CoV-2 163:172 SARS-CoV-2 163:172 SARS-CoV-2 163:172 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35233578 9 40 theme therapeutic 1364:1374 arg1 targets 1376:1382 potential therapeutic targets 1354:1382 potential therapeutic targets 1354:1382 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35233578 0 41 theme SARS-CoV-2 42:51 arg1 interactions 65:76 SARS-CoV-2 protein-RNA interactions 42:76 SARS-CoV-2 protein-RNA interactions 42:76 Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. 35233578 7 42 theme antiviral 1104:1112 arg1 targets 1119:1125 potential antiviral host targets 1094:1125 potential antiviral host targets across different SARS-CoV-2 variants 1094:1162 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 9 43 theme protein-RNA 1308:1318 arg1 interactome 1320:1330 Our viral protein-RNA interactome 1298:1330 Our viral protein-RNA interactome 1298:1330 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35233578 2 44 theme RNA 253:255 arg1 proteins 265:272 several RNA binding proteins 245:272 several RNA binding proteins 245:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35233578 5 45 theme unique 747:752 arg1 RNAs 766:769 4773 unique host coding RNAs 742:769 4773 unique host coding RNAs 742:769 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35233578 5 46 theme coding 759:764 arg1 RNAs 766:769 4773 unique host coding RNAs 742:769 4773 unique host coding RNAs 742:769 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35233578 2 47 theme several 245:251 arg1 proteins 265:272 several RNA binding proteins 245:272 several RNA binding proteins 245:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35233578 7 48 theme human 1059:1063 arg1 cells 1079:1083 human lung organoid cells 1059:1083 human lung organoid cells 1059:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 6 49 link N-linked 920:927 arg1 glycosylation 929:941 protein N-linked glycosylation ER processing and mitochondrial processes 912:983 glycosylation 929:941 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 0 50 theme interactions 65:76 arg1 Discovery 0:8 Discovery 0:8 Discovery 0:8 Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. 35233578 0 50 theme interactions 65:76 arg1 interrogation 25:37 functional interrogation 14:37 functional interrogation 14:37 Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. 35233578 4 51 theme viral 552:556 arg1 genome 558:563 the RNA viral genome 544:563 the RNA viral genome 544:563 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 5 52 theme human 706:710 arg1 cells 728:732 human lung epithelial cells 706:732 human lung epithelial cells 706:732 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35233578 6 53 theme protein 912:918 arg1 glycosylation 929:941 protein N-linked glycosylation ER processing and mitochondrial processes 912:983 glycosylation 929:941 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 1 54 theme acute 121:125 arg1 syndrome-coronavirus-2 139:160 severe acute respiratory syndrome-coronavirus-2 114:160 severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) 114:173 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35233578 1 54 theme acute 121:125 arg1 SARS-CoV-2 163:172 SARS-CoV-2 163:172 SARS-CoV-2 163:172 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35233578 0 55 theme protein-RNA 53:63 arg1 interactions 65:76 SARS-CoV-2 protein-RNA interactions 42:76 SARS-CoV-2 protein-RNA interactions 42:76 Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. 35233578 9 56 theme future 1456:1461 arg1 pandemics 1463:1471 future pandemics 1456:1471 future pandemics 1456:1471 Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics. 35233578 5 57 theme lung 712:715 arg1 cells 728:732 human lung epithelial cells 706:732 human lung epithelial cells 706:732 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35233578 6 58 theme SARS-CoV-2 777:786 arg1 proteins 788:795 Nine SARS-CoV-2 proteins 772:795 Nine SARS-CoV-2 proteins 772:795 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 1 59 theme respiratory 127:137 arg1 syndrome-coronavirus-2 139:160 severe acute respiratory syndrome-coronavirus-2 114:160 severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) 114:173 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35233578 1 59 theme respiratory 127:137 arg1 SARS-CoV-2 163:172 SARS-CoV-2 163:172 SARS-CoV-2 163:172 The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). 35233578 3 60 with interactions 368:379 arg1 RNAs 401:404 viral and host RNAs 386:404 viral and host RNAs 386:404 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35233578 5 61 theme epithelial 717:726 arg1 cells 728:732 human lung epithelial cells 706:732 human lung epithelial cells 706:732 SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. 35233578 6 62 theme RNA 865:867 arg1 substrates 869:878 RNA substrates 865:878 RNA substrates 865:878 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 8 63 theme mRNA 1224:1227 arg1 export 1229:1234 mRNA export 1224:1234 mRNA export 1224:1234 Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. 35233578 2 64 theme RNA 216:218 arg1 genome 220:225 a positive sense RNA genome 199:225 a positive sense RNA genome which encodes for several RNA binding proteins 199:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35233578 7 65 theme lung 1065:1068 arg1 cells 1079:1083 human lung organoid cells 1059:1083 human lung organoid cells 1059:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 7 66 theme SARS-CoV-2 1144:1153 arg1 variants 1155:1162 different SARS-CoV-2 variants 1134:1162 different SARS-CoV-2 variants 1134:1162 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 3 67 theme protein 360:366 arg1 interactions 368:379 SARS-CoV-2 protein interactions 349:379 SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells 349:438 Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. 35233578 2 68 theme sense 210:214 arg1 genome 220:225 a positive sense RNA genome 199:225 a positive sense RNA genome which encodes for several RNA binding proteins 199:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35233578 7 69 theme viral 1041:1045 arg1 proteins 1047:1054 viral proteins 1041:1054 viral proteins in human lung organoid cells 1041:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 6 70 dep glycosylation 929:941 arg1 processing 946:955 ER processing 943:955 ER processing 943:955 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 8 71 theme host 1191:1194 arg1 expression 1201:1210 host gene expression 1191:1210 host gene expression 1191:1210 Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. 35233578 6 72 theme mitochondrial 961:973 arg1 processes 975:983 mitochondrial processes 961:983 mitochondrial processes 961:983 Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. 35233578 2 73 theme binding 257:263 arg1 proteins 265:272 several RNA binding proteins 245:272 several RNA binding proteins 245:272 The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. 35233578 7 74 theme genes 1023:1027 arg1 knockdown 1005:1013 siRNA knockdown 999:1013 siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells 999:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 7 75 theme organoid 1070:1077 arg1 cells 1079:1083 human lung organoid cells 1059:1083 human lung organoid cells 1059:1083 Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. 35233578 4 76 from roles 615:619 arg1 packaging 662:670 viral packaging 656:670 viral packaging 656:670 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 4 76 from roles 615:619 arg1 transcription 637:649 transcription 637:649 transcription 637:649 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 35233578 4 76 from roles 615:619 arg1 replication 624:634 replication 624:634 replication 624:634 SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. 34998171 6 0 theme combinatorial 901:913 arg1 library 946:952 a combinatorial in vivo/in vitro phage display library 899:952 a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions 899:1004 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 9 1 theme galactosylated 1656:1669 arg1 glycans 1671:1677 the receptor terminal N-linked galactosylated glycans 1625:1677 the receptor terminal N-linked galactosylated glycans 1625:1677 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 7 2 theme AAV9 1113:1116 arg1 virions 1118:1124 AAV9 virions 1113:1124 AAV9 virions 1113:1124 The PB5-3 peptide specifically bound to AAV9 virions and enhanced widespread transduction of AAV9 in mouse brains, especially in neuronal cells, after systemic administration. 34998171 2 3 theme systemic 346:353 arg1 delivery 355:362 the noninvasive systemic delivery 330:362 the noninvasive systemic delivery of rAAV to the central nervous system 330:400 However, the noninvasive systemic delivery of rAAV to the central nervous system is severely hampered by the blood-brain barrier (BBB). 34998171 8 4 from correction 1381:1390 arg1 brains 1399:1404 the brains 1395:1404 the brains of MPS I mice 1395:1418 Further study demonstrated that systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 increased the phenotypic correction in the brains of MPS I mice. 34998171 12 5 theme new 2014:2016 arg1 avenues 2039:2045 new combined therapeutic avenues 2014:2045 new combined therapeutic avenues 2014:2045 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 11 6 theme targeted 1953:1960 arg1 transduction 1966:1977 enhanced and targeted AAV transduction 1940:1977 enhanced and targeted AAV transduction 1940:1977 This study highlights, for the first time, the potential of this combinatorial approach for the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction. 34998171 6 7 dep in 915:916 arg1 vitro 926:930 vitro 926:930 vitro 926:930 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 1 8 theme diseases 259:266 arg1 treatment 236:244 the treatment 232:244 the treatment of inherited diseases in clinical trials, including neurological diseases 232:318 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 12 9 theme therapeutic 2027:2037 arg1 avenues 2039:2045 new combined therapeutic avenues 2014:2045 new combined therapeutic avenues 2014:2045 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 12 10 theme future 2143:2148 arg1 trials 2159:2164 future clinical trials 2143:2164 future clinical trials with AAV vector-mediated gene delivery 2143:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 3 11 theme brain 518:522 arg1 transduction 524:535 AAV vector brain transduction 507:535 AAV vector brain transduction 507:535 Several approaches have been exploited to enhance AAV vector brain transduction after systemic administration, including genetic modification of AAV capsids and physical methods. 34998171 5 12 theme brain 853:857 arg1 transduction 859:870 enhanced brain transduction 844:870 enhanced brain transduction 844:870 It is imperative to explore novel strategies to increase the ability of AAV9 to cross the BBB for enhanced brain transduction. 34998171 12 13 theme promising 1985:1993 arg1 approach 1995:2002 This promising approach 1980:2002 This promising approach 1980:2002 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 7 14 theme AAV9 1166:1169 arg1 transduction 1150:1161 widespread transduction 1139:1161 widespread transduction of AAV9 in mouse brains, especially in neuronal cells 1139:1215 The PB5-3 peptide specifically bound to AAV9 virions and enhanced widespread transduction of AAV9 in mouse brains, especially in neuronal cells, after systemic administration. 34998171 9 15 theme PB5-3 1459:1463 arg1 peptide 1465:1471 the PB5-3 peptide 1455:1471 the PB5-3 peptide 1455:1471 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 10 16 from blood 1746:1750 arg1 clearance 1723:1731 the clearance 1719:1731 the clearance of AAV9 from blood 1719:1750 Additionally, the PB5-3 peptide slowed the clearance of AAV9 from blood without hepatic toxicity. 34998171 1 17 from diseases 259:266 arg1 trials 280:285 clinical trials 271:285 clinical trials 271:285 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 10 18 theme AAV9 1736:1739 arg1 clearance 1723:1731 the clearance 1719:1731 the clearance of AAV9 from blood 1719:1750 Additionally, the PB5-3 peptide slowed the clearance of AAV9 from blood without hepatic toxicity. 34998171 7 19 from brains 1180:1185 arg1 cells 1211:1215 neuronal cells 1202:1215 neuronal cells 1202:1215 The PB5-3 peptide specifically bound to AAV9 virions and enhanced widespread transduction of AAV9 in mouse brains, especially in neuronal cells, after systemic administration. 34998171 12 20 theme diseases 2131:2138 arg1 treatment 2112:2120 the treatment 2108:2120 the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery 2108:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 3 21 theme AAV 602:604 arg1 capsids 606:612 AAV capsids 602:612 AAV capsids 602:612 Several approaches have been exploited to enhance AAV vector brain transduction after systemic administration, including genetic modification of AAV capsids and physical methods. 34998171 1 22 theme favored 202:208 arg1 vehicles 219:226 favored delivery vehicles 202:226 favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases 202:318 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 1 22 theme favored 202:208 arg1 vectors 169:175 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 6 23 theme phage 932:936 arg1 library 946:952 a combinatorial in vivo/in vitro phage display library 899:952 a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions 899:1004 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 1 24 used used 194:197 arg2 vehicles 219:226 favored delivery vehicles 202:226 favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases 202:318 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 1 24 used used 194:197 arg2 vectors 169:175 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 12 25 theme peptides 2095:2102 arg1 applications 2079:2090 the potential applications 2065:2090 the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery 2065:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 11 26 theme AAV 1962:1964 arg1 transduction 1966:1977 enhanced and targeted AAV transduction 1940:1977 enhanced and targeted AAV transduction 1940:1977 This study highlights, for the first time, the potential of this combinatorial approach for the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction. 34998171 0 27 from transduction 100:111 arg1 brain 120:124 the brain 116:124 the brain 116:124 Customized blood-brain barrier shuttle peptide to increase AAV9 vector crossing the BBB and augment transduction in the brain. 34998171 8 28 theme AAV9 1308:1311 arg1 vectors 1313:1319 AAV9 vectors 1308:1319 AAV9 vectors encoding IDUA complexed with PB5-3 1308:1354 Further study demonstrated that systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 increased the phenotypic correction in the brains of MPS I mice. 34998171 3 29 theme methods 627:633 arg1 modification 586:597 genetic modification 578:597 genetic modification of AAV capsids and physical methods 578:633 Several approaches have been exploited to enhance AAV vector brain transduction after systemic administration, including genetic modification of AAV capsids and physical methods. 34998171 1 30 theme Recombinant 127:137 arg1 vectors 169:175 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 1 30 theme Recombinant 127:137 arg1 vehicles 219:226 favored delivery vehicles 202:226 favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases 202:318 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 9 31 theme Mechanistic 1421:1431 arg1 studies 1433:1439 Mechanistic studies 1421:1439 Mechanistic studies 1421:1439 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 1 32 theme virus 156:160 arg1 vectors 169:175 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 1 32 theme virus 156:160 arg1 vehicles 219:226 favored delivery vehicles 202:226 favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases 202:318 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 4 33 theme outcomes 701:708 arg1 predictive 677:686 predictive 677:686 predictive 677:686 However, these approaches are not always predictive of desirable outcomes in humans and induce complications. 34998171 5 34 theme novel 774:778 arg1 strategies 780:789 novel strategies 774:789 novel strategies 774:789 It is imperative to explore novel strategies to increase the ability of AAV9 to cross the BBB for enhanced brain transduction. 34998171 12 35 from trials 2159:2164 arg1 treatment 2112:2120 the treatment 2108:2120 the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery 2108:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 9 36 theme BBB 1553:1555 arg1 line 1577:1580 the human BBB model hCMEC/D3 cell line 1543:1580 the human BBB model hCMEC/D3 cell line 1543:1580 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 6 37 theme purified 984:991 arg1 virions 998:1004 purified AAV9 virions 984:1004 purified AAV9 virions 984:1004 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 9 38 theme hCMEC/D3 1563:1570 arg1 line 1577:1580 the human BBB model hCMEC/D3 cell line 1543:1580 the human BBB model hCMEC/D3 cell line 1543:1580 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 2 39 theme nervous 387:393 arg1 system 395:400 the central nervous system 375:400 the central nervous system 375:400 However, the noninvasive systemic delivery of rAAV to the central nervous system is severely hampered by the blood-brain barrier (BBB). 34998171 12 40 from diseases 2131:2138 arg1 trials 2159:2164 future clinical trials 2143:2164 future clinical trials with AAV vector-mediated gene delivery 2143:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 0 41 theme Customized 0:9 arg1 barrier 23:29 Customized blood-brain barrier 0:29 Customized blood-brain barrier 0:29 Customized blood-brain barrier shuttle peptide to increase AAV9 vector crossing the BBB and augment transduction in the brain. 34998171 7 42 theme PB5-3 1077:1081 arg1 peptide 1083:1089 The PB5-3 peptide 1073:1089 The PB5-3 peptide 1073:1089 The PB5-3 peptide specifically bound to AAV9 virions and enhanced widespread transduction of AAV9 in mouse brains, especially in neuronal cells, after systemic administration. 34998171 11 43 theme enhanced 1940:1947 arg1 transduction 1966:1977 enhanced and targeted AAV transduction 1940:1977 enhanced and targeted AAV transduction 1940:1977 This study highlights, for the first time, the potential of this combinatorial approach for the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction. 34998171 6 44 theme shuttle 1035:1041 arg1 peptide 1043:1049 a customized BBB shuttle peptide 1018:1049 a customized BBB shuttle peptide 1018:1049 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 7 45 theme widespread 1139:1148 arg1 transduction 1150:1161 widespread transduction 1139:1161 widespread transduction of AAV9 in mouse brains, especially in neuronal cells 1139:1215 The PB5-3 peptide specifically bound to AAV9 virions and enhanced widespread transduction of AAV9 in mouse brains, especially in neuronal cells, after systemic administration. 34998171 9 46 theme AAV9 1609:1612 arg1 binding 1614:1620 AAV9 binding 1609:1620 AAV9 binding to the receptor terminal N-linked galactosylated glycans 1609:1677 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 6 47 theme customized 1020:1029 arg1 peptide 1043:1049 a customized BBB shuttle peptide 1018:1049 a customized BBB shuttle peptide 1018:1049 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 8 48 theme I 1413:1413 arg1 mice 1415:1418 MPS I mice 1409:1418 MPS I mice 1409:1418 Further study demonstrated that systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 increased the phenotypic correction in the brains of MPS I mice. 34998171 2 49 theme noninvasive 334:344 arg1 delivery 355:362 the noninvasive systemic delivery 330:362 the noninvasive systemic delivery of rAAV to the central nervous system 330:400 However, the noninvasive systemic delivery of rAAV to the central nervous system is severely hampered by the blood-brain barrier (BBB). 34998171 12 50 theme AAV 2171:2173 arg1 delivery 2196:2203 AAV vector-mediated gene delivery 2171:2203 AAV vector-mediated gene delivery 2171:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 3 51 theme Several 457:463 arg1 approaches 465:474 Several approaches 457:474 Several approaches 457:474 Several approaches have been exploited to enhance AAV vector brain transduction after systemic administration, including genetic modification of AAV capsids and physical methods. 34998171 1 52 theme delivery 210:217 arg1 vehicles 219:226 favored delivery vehicles 202:226 favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases 202:318 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 1 52 theme delivery 210:217 arg1 vectors 169:175 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 10 53 theme hepatic 1760:1766 arg1 toxicity 1768:1775 hepatic toxicity 1760:1775 hepatic toxicity 1760:1775 Additionally, the PB5-3 peptide slowed the clearance of AAV9 from blood without hepatic toxicity. 34998171 9 54 theme receptor 1629:1636 arg1 glycans 1671:1677 the receptor terminal N-linked galactosylated glycans 1625:1677 the receptor terminal N-linked galactosylated glycans 1625:1677 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 12 55 theme gene 2191:2194 arg1 delivery 2196:2203 AAV vector-mediated gene delivery 2171:2203 AAV vector-mediated gene delivery 2171:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 2 56 theme rAAV 367:370 arg1 delivery 355:362 the noninvasive systemic delivery 330:362 the noninvasive systemic delivery of rAAV to the central nervous system 330:400 However, the noninvasive systemic delivery of rAAV to the central nervous system is severely hampered by the blood-brain barrier (BBB). 34998171 6 57 theme in 915:916 arg1 library 946:952 a combinatorial in vivo/in vitro phage display library 899:952 a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions 899:1004 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 9 58 theme N-linked 1647:1654 arg1 glycans 1671:1677 the receptor terminal N-linked galactosylated glycans 1625:1677 the receptor terminal N-linked galactosylated glycans 1625:1677 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 7 59 theme systemic 1224:1231 arg1 administration 1233:1246 systemic administration 1224:1246 systemic administration 1224:1246 The PB5-3 peptide specifically bound to AAV9 virions and enhanced widespread transduction of AAV9 in mouse brains, especially in neuronal cells, after systemic administration. 34998171 1 60 theme inherited 249:257 arg1 diseases 311:318 neurological diseases 298:318 neurological diseases 298:318 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 1 60 theme inherited 249:257 arg1 diseases 259:266 inherited diseases 249:266 inherited diseases 249:266 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 1 61 from trials 280:285 arg1 treatment 236:244 the treatment 232:244 the treatment of inherited diseases in clinical trials, including neurological diseases 232:318 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 3 62 theme vector 511:516 arg1 transduction 524:535 AAV vector brain transduction 507:535 AAV vector brain transduction 507:535 Several approaches have been exploited to enhance AAV vector brain transduction after systemic administration, including genetic modification of AAV capsids and physical methods. 34998171 5 63 theme enhanced 844:851 arg1 transduction 859:870 enhanced brain transduction 844:870 enhanced brain transduction 844:870 It is imperative to explore novel strategies to increase the ability of AAV9 to cross the BBB for enhanced brain transduction. 34998171 12 64 theme combined 2018:2025 arg1 avenues 2039:2045 new combined therapeutic avenues 2014:2045 new combined therapeutic avenues 2014:2045 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 7 65 theme neuronal 1202:1209 arg1 cells 1211:1215 neuronal cells 1202:1215 neuronal cells 1202:1215 The PB5-3 peptide specifically bound to AAV9 virions and enhanced widespread transduction of AAV9 in mouse brains, especially in neuronal cells, after systemic administration. 34998171 9 66 link N-linked 1647:1654 arg1 glycans 1671:1677 the receptor terminal N-linked galactosylated glycans 1625:1677 the receptor terminal N-linked galactosylated glycans 1625:1677 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 6 67 theme mouse 967:971 arg1 brains 973:978 mouse brains 967:978 mouse brains 967:978 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 12 68 theme clinical 2150:2157 arg1 trials 2159:2164 future clinical trials 2143:2164 future clinical trials with AAV vector-mediated gene delivery 2143:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 3 69 theme systemic 543:550 arg1 administration 552:565 systemic administration 543:565 systemic administration 543:565 Several approaches have been exploited to enhance AAV vector brain transduction after systemic administration, including genetic modification of AAV capsids and physical methods. 34998171 12 70 theme potential 2069:2077 arg1 applications 2079:2090 the potential applications 2065:2090 the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery 2065:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 8 71 theme Further 1249:1255 arg1 study 1257:1261 Further study 1249:1261 Further study 1249:1261 Further study demonstrated that systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 increased the phenotypic correction in the brains of MPS I mice. 34998171 11 72 theme first 1809:1813 arg1 time 1815:1818 the first time 1805:1818 the first time 1805:1818 This study highlights, for the first time, the potential of this combinatorial approach for the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction. 34998171 1 73 from treatment 236:244 arg1 trials 280:285 clinical trials 271:285 clinical trials 271:285 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 6 74 theme display 938:944 arg1 library 946:952 a combinatorial in vivo/in vitro phage display library 899:952 a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions 899:1004 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 12 75 theme human 2125:2129 arg1 diseases 2131:2138 human diseases 2125:2138 human diseases in future clinical trials with AAV vector-mediated gene delivery 2125:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 3 76 theme genetic 578:584 arg1 modification 586:597 genetic modification 578:597 genetic modification of AAV capsids and physical methods 578:633 Several approaches have been exploited to enhance AAV vector brain transduction after systemic administration, including genetic modification of AAV capsids and physical methods. 34998171 8 77 theme systemic 1281:1288 arg1 administration 1290:1303 systemic administration 1281:1303 systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 1281:1354 Further study demonstrated that systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 increased the phenotypic correction in the brains of MPS I mice. 34998171 3 78 theme physical 618:625 arg1 methods 627:633 physical methods 618:633 physical methods 618:633 Several approaches have been exploited to enhance AAV vector brain transduction after systemic administration, including genetic modification of AAV capsids and physical methods. 34998171 9 79 theme transcytosis 1516:1527 arg1 efficiency 1529:1538 transcytosis efficiency 1516:1538 transcytosis efficiency 1516:1538 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 11 80 theme combinatorial 1843:1855 arg1 approach 1857:1864 this combinatorial approach 1838:1864 this combinatorial approach 1838:1864 This study highlights, for the first time, the potential of this combinatorial approach for the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction. 34998171 3 81 theme capsids 606:612 arg1 modification 586:597 genetic modification 578:597 genetic modification of AAV capsids and physical methods 578:633 Several approaches have been exploited to enhance AAV vector brain transduction after systemic administration, including genetic modification of AAV capsids and physical methods. 34998171 1 82 theme adeno-associated 139:154 arg1 virus 156:160 adeno-associated virus 139:160 Recombinant adeno-associated virus (rAAV) vectors 127:175 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 1 82 theme adeno-associated 139:154 arg1 rAAV 163:166 rAAV 163:166 rAAV 163:166 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 8 83 theme vectors 1313:1319 arg1 administration 1290:1303 systemic administration 1281:1303 systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 1281:1354 Further study demonstrated that systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 increased the phenotypic correction in the brains of MPS I mice. 34998171 9 84 theme human 1547:1551 arg1 line 1577:1580 the human BBB model hCMEC/D3 cell line 1543:1580 the human BBB model hCMEC/D3 cell line 1543:1580 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 6 85 theme AAV9 993:996 arg1 virions 998:1004 purified AAV9 virions 984:1004 purified AAV9 virions 984:1004 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 4 86 theme desirable 691:699 arg1 outcomes 701:708 desirable outcomes 691:708 desirable outcomes in humans 691:718 However, these approaches are not always predictive of desirable outcomes in humans and induce complications. 34998171 9 87 theme model 1557:1561 arg1 line 1577:1580 the human BBB model hCMEC/D3 cell line 1543:1580 the human BBB model hCMEC/D3 cell line 1543:1580 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 7 88 from transduction 1150:1161 arg1 brains 1180:1185 mouse brains 1174:1185 mouse brains 1174:1185 The PB5-3 peptide specifically bound to AAV9 virions and enhanced widespread transduction of AAV9 in mouse brains, especially in neuronal cells, after systemic administration. 34998171 7 89 theme mouse 1174:1178 arg1 brains 1180:1185 mouse brains 1174:1185 mouse brains 1174:1185 The PB5-3 peptide specifically bound to AAV9 virions and enhanced widespread transduction of AAV9 in mouse brains, especially in neuronal cells, after systemic administration. 34998171 9 90 theme cell 1572:1575 arg1 line 1577:1580 the human BBB model hCMEC/D3 cell line 1543:1580 the human BBB model hCMEC/D3 cell line 1543:1580 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 2 91 theme central 379:385 arg1 system 395:400 the central nervous system 375:400 the central nervous system 375:400 However, the noninvasive systemic delivery of rAAV to the central nervous system is severely hampered by the blood-brain barrier (BBB). 34998171 0 92 theme blood-brain 11:21 arg1 barrier 23:29 Customized blood-brain barrier 0:29 Customized blood-brain barrier 0:29 Customized blood-brain barrier shuttle peptide to increase AAV9 vector crossing the BBB and augment transduction in the brain. 34998171 2 93 theme blood-brain 430:440 arg1 BBB 451:453 BBB 451:453 BBB 451:453 However, the noninvasive systemic delivery of rAAV to the central nervous system is severely hampered by the blood-brain barrier (BBB). 34998171 2 93 theme blood-brain 430:440 arg1 barrier 442:448 the blood-brain barrier 426:448 the blood-brain barrier (BBB) 426:454 However, the noninvasive systemic delivery of rAAV to the central nervous system is severely hampered by the blood-brain barrier (BBB). 34998171 8 94 theme phenotypic 1370:1379 arg1 correction 1381:1390 the phenotypic correction 1366:1390 the phenotypic correction in the brains of MPS I mice 1366:1418 Further study demonstrated that systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 increased the phenotypic correction in the brains of MPS I mice. 34998171 5 95 theme AAV9 818:821 arg1 ability 807:813 the ability 803:813 the ability of AAV9 to cross the BBB for enhanced brain transduction 803:870 It is imperative to explore novel strategies to increase the ability of AAV9 to cross the BBB for enhanced brain transduction. 34998171 1 96 theme clinical 271:278 arg1 trials 280:285 clinical trials 271:285 clinical trials 271:285 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 12 97 from treatment 2112:2120 arg1 trials 2159:2164 future clinical trials 2143:2164 future clinical trials with AAV vector-mediated gene delivery 2143:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 10 98 theme PB5-3 1698:1702 arg1 peptide 1704:1710 the PB5-3 peptide 1694:1710 the PB5-3 peptide 1694:1710 Additionally, the PB5-3 peptide slowed the clearance of AAV9 from blood without hepatic toxicity. 34998171 6 99 theme BBB 1031:1033 arg1 peptide 1043:1049 a customized BBB shuttle peptide 1018:1049 a customized BBB shuttle peptide 1018:1049 Herein, we have conducted a combinatorial in vivo/in vitro phage display library screening in mouse brains and purified AAV9 virions to identify a customized BBB shuttle peptide, designated as PB5-3. 34998171 11 100 theme specific 1915:1922 arg1 vectors 1928:1934 specific AAV vectors 1915:1934 specific AAV vectors for enhanced and targeted AAV transduction 1915:1977 This study highlights, for the first time, the potential of this combinatorial approach for the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction. 34998171 12 101 with trials 2159:2164 arg1 delivery 2196:2203 AAV vector-mediated gene delivery 2171:2203 AAV vector-mediated gene delivery 2171:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 0 102 theme AAV9 59:62 arg1 vector 64:69 AAV9 vector 59:69 AAV9 vector crossing the BBB 59:86 Customized blood-brain barrier shuttle peptide to increase AAV9 vector crossing the BBB and augment transduction in the brain. 34998171 1 103 theme neurological 298:309 arg1 diseases 311:318 neurological diseases 298:318 neurological diseases 298:318 Recombinant adeno-associated virus (rAAV) vectors have been widely used as favored delivery vehicles for the treatment of inherited diseases in clinical trials, including neurological diseases. 34998171 11 104 theme peptides 1887:1894 arg1 isolation 1874:1882 the isolation 1870:1882 the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction 1870:1977 This study highlights, for the first time, the potential of this combinatorial approach for the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction. 34998171 8 105 theme MPS 1409:1411 arg1 mice 1415:1418 MPS I mice 1409:1418 MPS I mice 1409:1418 Further study demonstrated that systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 increased the phenotypic correction in the brains of MPS I mice. 34998171 8 106 theme mice 1415:1418 arg1 brains 1399:1404 the brains 1395:1404 the brains of MPS I mice 1395:1418 Further study demonstrated that systemic administration of AAV9 vectors encoding IDUA complexed with PB5-3 increased the phenotypic correction in the brains of MPS I mice. 34998171 11 107 theme approach 1857:1864 arg1 potential 1825:1833 the potential 1821:1833 the potential of this combinatorial approach for the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction 1821:1977 This study highlights, for the first time, the potential of this combinatorial approach for the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction. 34998171 9 108 theme AAV9 1495:1498 arg1 trafficking 1500:1510 AAV9 trafficking 1495:1510 AAV9 trafficking 1495:1510 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 9 109 theme terminal 1638:1645 arg1 glycans 1671:1677 the receptor terminal N-linked galactosylated glycans 1625:1677 the receptor terminal N-linked galactosylated glycans 1625:1677 Mechanistic studies revealed that the PB5-3 peptide effectively increased AAV9 trafficking and transcytosis efficiency in the human BBB model hCMEC/D3 cell line but did not interfere with AAV9 binding to the receptor terminal N-linked galactosylated glycans. 34998171 11 110 theme AAV 1924:1926 arg1 vectors 1928:1934 specific AAV vectors 1915:1934 specific AAV vectors for enhanced and targeted AAV transduction 1915:1977 This study highlights, for the first time, the potential of this combinatorial approach for the isolation of peptides that interact with specific AAV vectors for enhanced and targeted AAV transduction. 34998171 12 111 theme vector-mediated 2175:2189 arg1 delivery 2196:2203 AAV vector-mediated gene delivery 2171:2203 AAV vector-mediated gene delivery 2171:2203 This promising approach will open new combined therapeutic avenues and shed light on the potential applications of peptides for the treatment of human diseases in future clinical trials with AAV vector-mediated gene delivery. 34998171 3 112 theme AAV 507:509 arg1 transduction 524:535 AAV vector brain transduction 507:535 AAV vector brain transduction 507:535 Several approaches have been exploited to enhance AAV vector brain transduction after systemic administration, including genetic modification of AAV capsids and physical methods. 34998171 4 113 from outcomes 701:708 arg1 humans 713:718 humans 713:718 humans 713:718 However, these approaches are not always predictive of desirable outcomes in humans and induce complications. 36651831 3 0 from abnormalities 580:592 arg1 histology 605:613 hepatic histology 597:613 hepatic histology 597:613 We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. 36651831 2 1 theme clinical 307:314 arg1 updates 316:322 clinical updates 307:322 clinical updates 307:322 Here, we present eleven new patients and clinical updates with biochemical characterization on one previously reported patient. 36651831 8 2 from tool 1648:1651 arg1 diagnosis 1656:1664 diagnosis 1656:1664 diagnosis 1656:1664 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 8 2 from tool 1648:1651 arg1 monitoring 1678:1687 disease monitoring 1670:1687 disease monitoring 1670:1687 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 6 3 link N-linked 923:930 arg1 glycosylation 932:944 The aberrant N-linked glycosylation 910:944 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions 910:1012 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 6 4 theme hepatic 1045:1051 arg1 transplant 1053:1062 hepatic transplant 1045:1062 hepatic transplant 1045:1062 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 5 5 theme fractionated 726:737 arg1 proteins 746:753 fractionated plasma proteins 726:753 fractionated plasma proteins 726:753 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 6 6 theme N-linked 923:930 arg1 glycosylation 932:944 The aberrant N-linked glycosylation 910:944 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions 910:1012 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 6 7 gly glycosylation 932:944 arg1 fractions 1004:1012 purified transferrin and remaining plasma glycoprotein fractions 949:1012 fractions 1004:1012 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 6 7 gly glycosylation 932:944 arg1 transferrin 958:968 purified transferrin and remaining plasma glycoprotein fractions 949:1012 transferrin 958:968 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 5 8 theme proteins 746:753 arg1 profiling 703:711 N-glycan profiling 694:711 N-glycan profiling of total and fractionated plasma proteins for six patients 694:770 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 1 9 theme abnormal 214:221 arg1 pattern 257:263 an abnormal type II transferrin glycosylation pattern 211:263 an abnormal type II transferrin glycosylation pattern 211:263 ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern. 36651831 8 10 theme diverse 1416:1422 arg1 presentations 1459:1471 the diverse and often tissue specific clinical presentations 1412:1471 the diverse and often tissue specific clinical presentations 1412:1471 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 8 11 theme management 1498:1507 arg1 presentations 1459:1471 the diverse and often tissue specific clinical presentations 1412:1471 the diverse and often tissue specific clinical presentations 1412:1471 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 8 11 theme management 1498:1507 arg1 need 1481:1484 the need 1477:1484 the need of clinical management post hepatic transplant in ATP6AP1-CDG patients 1477:1555 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 5 12 theme potential 833:841 arg1 value 869:873 potential diagnostic and prognostic value 833:873 potential diagnostic and prognostic value of fractionated N-glycan profiles 833:907 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 1 13 theme glycosylation 243:255 arg1 pattern 257:263 an abnormal type II transferrin glycosylation pattern 211:263 an abnormal type II transferrin glycosylation pattern 211:263 ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern. 36651831 8 14 theme specific 1441:1448 arg1 presentations 1459:1471 the diverse and often tissue specific clinical presentations 1412:1471 the diverse and often tissue specific clinical presentations 1412:1471 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 8 15 theme hepatic 1514:1520 arg1 transplant 1522:1531 hepatic transplant 1514:1531 hepatic transplant in ATP6AP1-CDG patients 1514:1555 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 1 16 theme X-linked 132:139 arg1 disorder 141:148 an X-linked disorder 129:148 an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern 129:263 ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern. 36651831 1 16 theme X-linked 132:139 arg1 ATP6AP1-CDG 114:124 ATP6AP1-CDG 114:124 ATP6AP1-CDG 114:124 ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern. 36651831 5 17 theme varying 799:805 arg1 phenotypes 807:816 varying phenotypes 799:816 varying phenotypes 799:816 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 2 18 with patients 294:301 arg1 characterization 341:356 biochemical characterization 329:356 biochemical characterization on one previously reported patient 329:391 Here, we present eleven new patients and clinical updates with biochemical characterization on one previously reported patient. 36651831 5 19 theme fractionated 878:889 arg1 profiles 900:907 fractionated N-glycan profiles 878:907 fractionated N-glycan profiles 878:907 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 7 20 theme plasma 1375:1380 arg1 fractions 1395:1403 the remaining plasma glycoprotein fractions 1361:1403 the remaining plasma glycoprotein fractions 1361:1403 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 7 21 theme immune 1206:1211 arg1 phenotype 1224:1232 isolated immune deficiency phenotype 1197:1232 isolated immune deficiency phenotype 1197:1232 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 5 22 theme profiles 900:907 arg1 value 869:873 potential diagnostic and prognostic value 833:873 potential diagnostic and prognostic value of fractionated N-glycan profiles 833:907 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 5 23 theme N-glycan 694:701 arg1 profiling 703:711 N-glycan profiling 694:711 N-glycan profiling of total and fractionated plasma proteins for six patients 694:770 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 8 24 theme fractionated 1589:1600 arg1 tool 1648:1651 a valuable tool 1637:1651 a valuable tool in diagnosis and disease monitoring 1637:1687 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 8 24 theme fractionated 1589:1600 arg1 profiling 1618:1626 fractionated plasma N-glycan profiling 1589:1626 fractionated plasma N-glycan profiling 1589:1626 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 6 25 gly glycoprotein 991:1002 arg1 glycoprotein 991:1002 purified transferrin and remaining plasma glycoprotein fractions 949:1012 glycoprotein 991:1002 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 6 26 from glycosylation 932:944 arg1 fractions 1004:1012 purified transferrin and remaining plasma glycoprotein fractions 949:1012 fractions 1004:1012 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 6 26 from glycosylation 932:944 arg1 transferrin 958:968 purified transferrin and remaining plasma glycoprotein fractions 949:1012 transferrin 958:968 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 7 27 from fractions 1395:1403 arg1 transferrin 1346:1356 transferrin 1346:1356 transferrin 1346:1356 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 8 28 theme N-glycan 1609:1616 arg1 tool 1648:1651 a valuable tool 1637:1651 a valuable tool in diagnosis and disease monitoring 1637:1687 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 8 28 theme N-glycan 1609:1616 arg1 profiling 1618:1626 fractionated plasma N-glycan profiling 1589:1626 fractionated plasma N-glycan profiling 1589:1626 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 0 29 theme Fractionated 0:11 arg1 profiling 29:37 Fractionated plasma N-glycan profiling 0:37 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects 0:77 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association. 36651831 5 30 with associations 781:792 arg1 phenotypes 807:816 varying phenotypes 799:816 varying phenotypes 799:816 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 3 31 theme intrafamilial 411:423 arg1 variability 436:446 intrafamilial phenotypic variability 411:446 intrafamilial phenotypic variability 411:446 We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. 36651831 4 32 theme subjects 629:636 arg1 Three 616:620 Three 616:620 Three 616:620 Three of our subjects received successful liver transplantation. 36651831 4 32 theme subjects 629:636 arg1 subjects 629:636 our subjects 625:636 our subjects 625:636 Three of our subjects received successful liver transplantation. 36651831 0 33 theme N-glycan 20:27 arg1 profiling 29:37 Fractionated plasma N-glycan profiling 0:37 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects 0:77 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association. 36651831 4 34 theme successful 647:656 arg1 transplantation 664:678 successful liver transplantation 647:678 successful liver transplantation 647:678 Three of our subjects received successful liver transplantation. 36651831 3 35 theme atypical 452:459 arg1 presentations 461:473 atypical presentations 452:473 atypical presentations 452:473 We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. 36651831 0 36 theme ATP6AP1-CDG 58:68 arg1 subjects 70:77 ATP6AP1-CDG subjects 58:77 ATP6AP1-CDG subjects 58:77 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association. 36651831 0 37 theme cohort 48:53 arg1 profiling 29:37 Fractionated plasma N-glycan profiling 0:37 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects 0:77 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association. 36651831 6 38 theme glycoprotein 991:1002 arg1 fractions 1004:1012 purified transferrin and remaining plasma glycoprotein fractions 949:1012 fractions 1004:1012 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 7 39 theme purified 1282:1289 arg1 immunoglobulins 1291:1305 purified immunoglobulins 1282:1305 purified immunoglobulins without glycosylation abnormalities on transferrin 1282:1356 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 3 40 theme hepatocellular 541:554 arg1 carcinoma 556:564 hepatocellular carcinoma 541:564 hepatocellular carcinoma 541:564 We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. 36651831 6 41 theme remaining 974:982 arg1 fractions 1004:1012 purified transferrin and remaining plasma glycoprotein fractions 949:1012 fractions 1004:1012 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 8 42 theme disease 1670:1676 arg1 monitoring 1678:1687 disease monitoring 1670:1687 disease monitoring 1670:1687 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 3 43 theme hepatic 597:603 arg1 histology 605:613 hepatic histology 597:613 hepatic histology 597:613 We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. 36651831 6 44 from increases 1075:1083 arg1 immunoglobulins 1128:1142 purified immunoglobulins 1119:1142 purified immunoglobulins 1119:1142 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 5 45 theme N-glycan 891:898 arg1 profiles 900:907 fractionated N-glycan profiles 878:907 fractionated N-glycan profiles 878:907 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 7 46 theme glycosylation 1315:1327 arg1 abnormalities 1329:1341 glycosylation abnormalities 1315:1341 glycosylation abnormalities 1315:1341 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 3 47 from carcinoma 556:564 arg1 histology 605:613 hepatic histology 597:613 hepatic histology 597:613 We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. 36651831 6 48 theme purified 949:956 arg1 transferrin 958:968 purified transferrin and remaining plasma glycoprotein fractions 949:1012 transferrin 958:968 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 8 49 theme clinical 1450:1457 arg1 presentations 1459:1471 the diverse and often tissue specific clinical presentations 1412:1471 the diverse and often tissue specific clinical presentations 1412:1471 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 5 50 theme plasma 739:744 arg1 proteins 746:753 fractionated plasma proteins 726:753 fractionated plasma proteins 726:753 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 6 51 theme aberrant 914:921 arg1 glycosylation 932:944 The aberrant N-linked glycosylation 910:944 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions 910:1012 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 7 52 theme high-mannose 1244:1255 arg1 glycans 1257:1263 elevated high-mannose glycans 1235:1263 elevated high-mannose glycans 1235:1263 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 2 53 theme biochemical 329:339 arg1 characterization 341:356 biochemical characterization 329:356 biochemical characterization on one previously reported patient 329:391 Here, we present eleven new patients and clinical updates with biochemical characterization on one previously reported patient. 36651831 1 54 theme type 223:226 arg1 pattern 257:263 an abnormal type II transferrin glycosylation pattern 211:263 an abnormal type II transferrin glycosylation pattern 211:263 ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern. 36651831 6 55 theme purified 1119:1126 arg1 immunoglobulins 1128:1142 purified immunoglobulins 1119:1142 purified immunoglobulins 1119:1142 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 2 56 theme reported 376:383 arg1 patient 385:391 one previously reported patient 361:391 one previously reported patient 361:391 Here, we present eleven new patients and clinical updates with biochemical characterization on one previously reported patient. 36651831 1 57 theme transferrin 231:241 arg1 pattern 257:263 an abnormal type II transferrin glycosylation pattern 211:263 an abnormal type II transferrin glycosylation pattern 211:263 ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern. 36651831 6 58 theme Man5GlcNAc2 1104:1114 arg1 increases 1075:1083 the increases 1071:1083 the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins 1071:1142 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 8 59 theme clinical 1489:1496 arg1 management 1498:1507 clinical management 1489:1507 clinical management 1489:1507 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 7 60 theme deficiency 1213:1222 arg1 phenotype 1224:1232 isolated immune deficiency phenotype 1197:1232 isolated immune deficiency phenotype 1197:1232 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 6 61 theme Man4GlcNAc2 1088:1098 arg1 increases 1075:1083 the increases 1071:1083 the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins 1071:1142 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 7 62 theme isolated 1197:1204 arg1 phenotype 1224:1232 isolated immune deficiency phenotype 1197:1232 isolated immune deficiency phenotype 1197:1232 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 2 63 theme new 290:292 arg1 patients 294:301 eleven new patients 283:301 eleven new patients 283:301 Here, we present eleven new patients and clinical updates with biochemical characterization on one previously reported patient. 36651831 7 64 theme single 1177:1182 arg1 patient 1184:1190 the single patient 1173:1190 the single patient with isolated immune deficiency phenotype 1173:1232 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 7 65 located detected 1270:1277 arg2 glycans 1257:1263 elevated high-mannose glycans 1235:1263 elevated high-mannose glycans 1235:1263 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 7 65 located detected 1270:1277 arg1 patient 1184:1190 the single patient 1173:1190 the single patient with isolated immune deficiency phenotype 1173:1232 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 7 65 located detected 1270:1277 arg1 immunoglobulins 1291:1305 purified immunoglobulins 1282:1305 purified immunoglobulins without glycosylation abnormalities on transferrin 1282:1356 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 7 65 located detected 1270:1277 arg1 fractions 1395:1403 the remaining plasma glycoprotein fractions 1361:1403 the remaining plasma glycoprotein fractions 1361:1403 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 0 66 theme subjects 70:77 arg1 cohort 48:53 novel cohort 42:53 novel cohort of ATP6AP1-CDG subjects 42:77 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association. 36651831 2 67 with updates 316:322 arg1 characterization 341:356 biochemical characterization 329:356 biochemical characterization on one previously reported patient 329:391 Here, we present eleven new patients and clinical updates with biochemical characterization on one previously reported patient. 36651831 8 68 theme ATP6AP1-CDG 1536:1546 arg1 patients 1548:1555 ATP6AP1-CDG patients 1536:1555 ATP6AP1-CDG patients 1536:1555 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 0 69 theme phenotypic 90:99 arg1 association 101:111 phenotypic association 90:111 phenotypic association 90:111 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association. 36651831 5 70 theme diagnostic 843:852 arg1 value 869:873 potential diagnostic and prognostic value 833:873 potential diagnostic and prognostic value of fractionated N-glycan profiles 833:907 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 8 71 from transplant 1522:1531 arg1 patients 1548:1555 ATP6AP1-CDG patients 1536:1555 ATP6AP1-CDG patients 1536:1555 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 2 72 from characterization 341:356 arg1 patient 385:391 one previously reported patient 361:391 one previously reported patient 361:391 Here, we present eleven new patients and clinical updates with biochemical characterization on one previously reported patient. 36651831 7 73 with patient 1184:1190 arg1 phenotype 1224:1232 isolated immune deficiency phenotype 1197:1232 isolated immune deficiency phenotype 1197:1232 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 5 74 theme prognostic 858:867 arg1 value 869:873 potential diagnostic and prognostic value 833:873 potential diagnostic and prognostic value of fractionated N-glycan profiles 833:907 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 5 75 theme total 716:720 arg1 profiling 703:711 N-glycan profiling 694:711 N-glycan profiling of total and fractionated plasma proteins for six patients 694:770 We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. 36651831 3 76 theme ATP6AP1-CDG 508:518 arg1 symptomatology 490:503 the symptomatology 486:503 the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology 486:613 We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. 36651831 0 77 theme plasma 13:18 arg1 profiling 29:37 Fractionated plasma N-glycan profiling 0:37 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects 0:77 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association. 36651831 8 78 theme plasma 1602:1607 arg1 tool 1648:1651 a valuable tool 1637:1651 a valuable tool in diagnosis and disease monitoring 1637:1687 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 8 78 theme plasma 1602:1607 arg1 profiling 1618:1626 fractionated plasma N-glycan profiling 1589:1626 fractionated plasma N-glycan profiling 1589:1626 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 7 79 theme remaining 1365:1373 arg1 fractions 1395:1403 the remaining plasma glycoprotein fractions 1361:1403 the remaining plasma glycoprotein fractions 1361:1403 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 3 80 theme phenotypic 425:434 arg1 variability 436:446 intrafamilial phenotypic variability 411:446 intrafamilial phenotypic variability 411:446 We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. 36651831 4 81 theme liver 658:662 arg1 transplantation 664:678 successful liver transplantation 647:678 successful liver transplantation 647:678 Three of our subjects received successful liver transplantation. 36651831 0 82 theme novel 42:46 arg1 cohort 48:53 novel cohort 42:53 novel cohort of ATP6AP1-CDG subjects 42:77 Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association. 36651831 7 83 from immunoglobulins 1291:1305 arg1 transferrin 1346:1356 transferrin 1346:1356 transferrin 1346:1356 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 7 84 theme elevated 1235:1242 arg1 glycans 1257:1263 elevated high-mannose glycans 1235:1263 elevated high-mannose glycans 1235:1263 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 8 85 theme valuable 1639:1646 arg1 tool 1648:1651 a valuable tool 1637:1651 a valuable tool in diagnosis and disease monitoring 1637:1687 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 8 85 theme valuable 1639:1646 arg1 profiling 1618:1626 fractionated plasma N-glycan profiling 1589:1626 fractionated plasma N-glycan profiling 1589:1626 Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring. 36651831 3 86 from dystonia 531:538 arg1 histology 605:613 hepatic histology 597:613 hepatic histology 597:613 We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. 36651831 3 87 theme lysosomal 570:578 arg1 abnormalities 580:592 lysosomal abnormalities 570:592 lysosomal abnormalities 570:592 We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. 36651831 6 88 theme plasma 984:989 arg1 fractions 1004:1012 purified transferrin and remaining plasma glycoprotein fractions 949:1012 fractions 1004:1012 The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. 36651831 1 89 link X-linked 132:139 arg1 disorder 141:148 an X-linked disorder 129:148 an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern 129:263 ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern. 36651831 1 89 link X-linked 132:139 arg1 ATP6AP1-CDG 114:124 ATP6AP1-CDG 114:124 ATP6AP1-CDG 114:124 ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern. 36651831 7 90 gly glycoprotein 1382:1393 arg1 glycoprotein 1382:1393 the remaining plasma glycoprotein fractions 1361:1403 the remaining plasma glycoprotein fractions 1361:1403 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 36651831 7 91 theme glycoprotein 1382:1393 arg1 fractions 1395:1403 the remaining plasma glycoprotein fractions 1361:1403 the remaining plasma glycoprotein fractions 1361:1403 Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. 33827945 6 0 theme recall 915:920 arg1 responses 922:930 recall responses 915:930 recall responses 915:930 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 8 1 theme influenza 1533:1541 arg1 antigen 1549:1555 the same influenza virus antigen 1524:1555 the same influenza virus antigen 1524:1555 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 6 2 theme improved 1078:1085 arg1 outcomes 1096:1103 improved clinical outcomes 1078:1103 improved clinical outcomes 1078:1103 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 5 3 theme memory 659:664 arg1 cells 669:673 these NKp46+ NKG2A+ memory NK cells 639:673 these NKp46+ NKG2A+ memory NK cells 639:673 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 7 4 theme long-lived 1111:1120 arg1 memory 1125:1130 This long-lived NK memory 1106:1130 This long-lived NK memory 1106:1130 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 2 5 theme immunity 276:283 arg1 roles 260:264 the roles 256:264 the roles of innate immunity in recall responses 256:303 In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. 33827945 9 6 theme immune 1661:1666 arg1 responses 1688:1696 the innate immune and adaptive immune responses 1650:1696 the innate immune and adaptive immune responses 1650:1696 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 5 7 theme protein 868:874 arg1 pifithrin-μ 838:848 pifithrin-μ 838:848 pifithrin-μ 838:848 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 5 7 theme protein 868:874 arg1 inhibitor 897:905 a p53-heat shock protein 70 (HSP70) signaling inhibitor 851:905 a p53-heat shock protein 70 (HSP70) signaling inhibitor 851:905 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 9 8 theme adaptive 1672:1679 arg1 responses 1688:1696 the innate immune and adaptive immune responses 1650:1696 the innate immune and adaptive immune responses 1650:1696 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 5 9 theme NKp46+ 645:650 arg1 cells 669:673 these NKp46+ NKG2A+ memory NK cells 639:673 these NKp46+ NKG2A+ memory NK cells 639:673 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 1 10 theme pathogens 208:216 arg1 transmission 181:192 transmission 181:192 transmission 181:192 Immune memory represents the most efficient defense against invasion and transmission of infectious pathogens. 33827945 1 10 theme pathogens 208:216 arg1 invasion 168:175 invasion 168:175 invasion 168:175 Immune memory represents the most efficient defense against invasion and transmission of infectious pathogens. 33827945 7 11 theme virus 1385:1389 arg1 infection 1391:1399 influenza A virus infection 1373:1399 influenza A virus infection 1373:1399 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 2 12 dep T 241:241 arg1 contrast 222:229 contrast 222:229 contrast 222:229 In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. 33827945 2 13 theme recall 288:293 arg1 responses 295:303 recall responses 288:303 recall responses 288:303 In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. 33827945 6 14 theme NK 955:956 arg1 cells 958:962 splenic NKp46+ NKG2A+ NK cells 933:962 splenic NKp46+ NKG2A+ NK cells 933:962 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 9 15 theme influenza 1705:1713 arg1 infection 1721:1729 influenza virus infection 1705:1729 influenza virus infection 1705:1729 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 8 16 theme virus-specific 1429:1442 arg1 cytotoxicity 1454:1465 virus-specific decreased cytotoxicity 1429:1465 virus-specific decreased cytotoxicity 1429:1465 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 7 17 theme influenza 1373:1381 arg1 virus 1385:1389 influenza A virus 1373:1389 influenza A virus infection 1373:1399 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 5 18 theme p53-heat 853:860 arg1 protein 868:874 p53-heat shock protein 70 853:877 a p53-heat shock protein 70 (HSP70) signaling inhibitor 851:905 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 5 18 theme p53-heat 853:860 arg1 HSP70 880:884 HSP70 880:884 HSP70 880:884 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 7 19 theme NK 1122:1123 arg1 memory 1125:1130 This long-lived NK memory 1106:1130 This long-lived NK memory 1106:1130 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 6 20 theme NKp46+ 941:946 arg1 cells 958:962 splenic NKp46+ NKG2A+ NK cells 933:962 splenic NKp46+ NKG2A+ NK cells 933:962 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 5 21 theme HA-specific 685:695 arg1 silence 697:703 HA-specific silence 685:703 HA-specific silence of cytotoxicity 685:719 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 2 22 theme memory 234:239 arg1 T 241:241 memory T and B cells 234:253 T 241:241 In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. 33827945 8 23 theme increased 1471:1479 arg1 IFN-γ 1499:1503 IFN-γ 1499:1503 IFN-γ 1499:1503 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 8 23 theme increased 1471:1479 arg1 interferon 1487:1496 increased gamma interferon 1471:1496 increased gamma interferon (IFN-γ) 1471:1504 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 7 24 theme cell 1350:1353 arg1 subset 1355:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset 1297:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection 1297:1399 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 4 25 gly glycosylation 521:533 arg2 sites 535:539 N-linked glycosylation sites 512:539 N-linked glycosylation sites on influenza hemagglutinin (HA) protein 512:579 These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. 33827945 1 26 theme efficient 142:150 arg1 defense 152:158 the most efficient defense 133:158 the most efficient defense against invasion and transmission of infectious pathogens 133:216 Immune memory represents the most efficient defense against invasion and transmission of infectious pathogens. 33827945 7 27 theme NKG2A+ 1340:1345 arg1 subset 1355:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset 1297:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection 1297:1399 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 5 28 theme response 762:769 arg1 increase 725:732 increase 725:732 increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor 725:905 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 0 29 theme Functional 15:24 arg1 Characteristics 26:40 Phenotypic and Functional Characteristics 0:40 Phenotypic and Functional Characteristics of a Novel Influenza Virus 0:67 Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell. 33827945 0 30 theme Memory 92:97 arg1 Cell 102:105 Hemagglutinin-Specific Memory NK Cell 69:105 Hemagglutinin-Specific Memory NK Cell 69:105 Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell. 33827945 5 31 theme memory-like 597:607 arg1 cells 612:616 memory-like NK cells 597:616 memory-like NK cells reported previously 597:636 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 5 32 theme interferon 743:752 arg1 response 762:769 gamma interferon (IFN-γ) response 737:769 gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor 737:905 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 5 33 theme virus-infected 789:802 arg1 cells 804:808 influenza virus-infected cells 779:808 influenza virus-infected cells 779:808 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 0 34 dep Cell 102:105 arg1 Characteristics 26:40 Phenotypic and Functional Characteristics 0:40 Phenotypic and Functional Characteristics of a Novel Influenza Virus 0:67 Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell. 33827945 7 35 theme NKp46+ 1333:1338 arg1 subset 1355:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset 1297:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection 1297:1399 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 3 36 theme spleen 369:374 arg1 subset 384:389 a novel mouse spleen NK cell subset 355:389 a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection 355:464 In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. 33827945 4 37 theme memory 473:478 arg1 cells 483:487 These memory NK cells 467:487 These memory NK cells 467:487 These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. 33827945 0 38 theme Hemagglutinin-Specific 69:90 arg1 Cell 102:105 Hemagglutinin-Specific Memory NK Cell 69:105 Hemagglutinin-Specific Memory NK Cell 69:105 Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell. 33827945 0 39 theme Phenotypic 0:9 arg1 Characteristics 26:40 Phenotypic and Functional Characteristics 0:40 Phenotypic and Functional Characteristics of a Novel Influenza Virus 0:67 Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell. 33827945 6 40 theme cell 1046:1049 arg1 clearance 1016:1024 viral clearance 1010:1024 viral clearance of virus and CD8+ T cell distribution 1010:1062 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 3 41 theme novel 357:361 arg1 subset 384:389 a novel mouse spleen NK cell subset 355:389 a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection 355:464 In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. 33827945 4 42 theme hemagglutinin 554:566 arg1 protein 573:579 influenza hemagglutinin (HA) protein 544:579 influenza hemagglutinin (HA) protein 544:579 These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. 33827945 3 43 theme virus 450:454 arg1 infection 456:464 intranasal influenza virus infection 429:464 intranasal influenza virus infection 429:464 In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. 33827945 7 44 theme immune 1160:1165 arg1 response 1174:1181 innate and adaptive immune memory response 1140:1181 innate and adaptive immune memory response 1140:1181 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 9 45 theme host 1585:1588 arg1 responses 1597:1605 host recall responses 1585:1605 host recall responses 1585:1605 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 2 46 from roles 260:264 arg1 responses 295:303 recall responses 288:303 recall responses 288:303 In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. 33827945 6 47 theme CD8+ 1039:1042 arg1 cell 1046:1049 CD8+ T cell 1039:1049 CD8+ T cell 1039:1049 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 3 48 theme intranasal 429:438 arg1 infection 456:464 intranasal influenza virus infection 429:464 intranasal influenza virus infection 429:464 In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. 33827945 7 49 theme novel 1299:1303 arg1 subset 1355:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset 1297:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection 1297:1399 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 3 50 theme cell 379:382 arg1 subset 384:389 a novel mouse spleen NK cell subset 355:389 a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection 355:464 In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. 33827945 4 51 theme glycosylation 521:533 arg1 sites 535:539 N-linked glycosylation sites 512:539 N-linked glycosylation sites on influenza hemagglutinin (HA) protein 512:579 These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. 33827945 0 52 theme Virus 63:67 arg1 Characteristics 26:40 Phenotypic and Functional Characteristics 0:40 Phenotypic and Functional Characteristics of a Novel Influenza Virus 0:67 Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell. 33827945 0 53 theme Novel 47:51 arg1 Virus 63:67 a Novel Influenza Virus 45:67 a Novel Influenza Virus 45:67 Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell. 33827945 9 54 theme CD8 1611:1613 arg1 distribution 1622:1633 CD8 T cell distribution 1611:1633 CD8 T cell distribution 1611:1633 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 8 55 theme NK 1415:1416 arg1 cells 1418:1422 These memory NK cells 1402:1422 These memory NK cells 1402:1422 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 9 56 theme cell 1617:1620 arg1 distribution 1622:1633 CD8 T cell distribution 1611:1633 CD8 T cell distribution 1611:1633 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 6 57 theme virus 1029:1033 arg1 clearance 1016:1024 viral clearance 1010:1024 viral clearance of virus and CD8+ T cell distribution 1010:1062 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 0 58 theme Influenza 53:61 arg1 Virus 63:67 a Novel Influenza Virus 45:67 a Novel Influenza Virus 45:67 Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell. 33827945 6 59 theme clinical 1087:1094 arg1 outcomes 1096:1103 improved clinical outcomes 1078:1103 improved clinical outcomes 1078:1103 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 5 60 theme NKG2A+ 652:657 arg1 cells 669:673 these NKp46+ NKG2A+ memory NK cells 639:673 these NKp46+ NKG2A+ memory NK cells 639:673 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 5 61 theme NK 666:667 arg1 cells 669:673 these NKp46+ NKG2A+ memory NK cells 639:673 these NKp46+ NKG2A+ memory NK cells 639:673 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 9 62 theme innate 1654:1659 arg1 responses 1688:1696 the innate immune and adaptive immune responses 1650:1696 the innate immune and adaptive immune responses 1650:1696 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 2 63 theme innate 269:274 arg1 immunity 276:283 innate immunity 269:283 innate immunity 269:283 In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. 33827945 5 64 theme shock 862:866 arg1 protein 868:874 p53-heat shock protein 70 853:877 a p53-heat shock protein 70 (HSP70) signaling inhibitor 851:905 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 5 64 theme shock 862:866 arg1 HSP70 880:884 HSP70 880:884 HSP70 880:884 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 5 65 theme influenza 779:787 arg1 cells 804:808 influenza virus-infected cells 779:808 influenza virus-infected cells 779:808 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 7 66 theme local 1215:1219 arg1 environment 1221:1231 local environment 1215:1231 local environment 1215:1231 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 1 67 theme infectious 197:206 arg1 pathogens 208:216 infectious pathogens 197:216 infectious pathogens 197:216 Immune memory represents the most efficient defense against invasion and transmission of infectious pathogens. 33827945 4 68 link N-linked 512:519 arg1 sites 535:539 N-linked glycosylation sites 512:539 N-linked glycosylation sites on influenza hemagglutinin (HA) protein 512:579 These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. 33827945 9 69 theme immune 1681:1686 arg1 responses 1688:1696 the innate immune and adaptive immune responses 1650:1696 the innate immune and adaptive immune responses 1650:1696 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 5 70 theme cytotoxicity 708:719 arg1 silence 697:703 HA-specific silence 685:703 HA-specific silence of cytotoxicity 685:719 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 8 71 theme decreased 1444:1452 arg1 cytotoxicity 1454:1465 virus-specific decreased cytotoxicity 1429:1465 virus-specific decreased cytotoxicity 1429:1465 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 2 72 theme B 247:247 arg1 cells 249:253 memory T and B cells 234:253 cells 249:253 In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. 33827945 6 73 theme NKG2A+ 948:953 arg1 cells 958:962 splenic NKp46+ NKG2A+ NK cells 933:962 splenic NKp46+ NKG2A+ NK cells 933:962 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 9 74 theme virus 1715:1719 arg1 infection 1721:1729 influenza virus infection 1705:1729 influenza virus infection 1705:1729 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 7 75 theme A 1383:1383 arg1 virus 1385:1389 influenza A virus 1373:1389 influenza A virus infection 1373:1399 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 6 76 theme splenic 933:939 arg1 cells 958:962 splenic NKp46+ NKG2A+ NK cells 933:962 splenic NKp46+ NKG2A+ NK cells 933:962 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 8 77 theme gamma 1481:1485 arg1 IFN-γ 1499:1503 IFN-γ 1499:1503 IFN-γ 1499:1503 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 8 77 theme gamma 1481:1485 arg1 interferon 1487:1496 increased gamma interferon 1471:1496 increased gamma interferon (IFN-γ) 1471:1504 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 7 78 theme environment 1221:1231 arg1 homeostasis 1200:1210 the homeostasis 1196:1210 the homeostasis of local environment 1196:1231 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 5 79 from cells 612:616 arg1 Different 582:590 Different 582:590 Different 582:590 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 6 80 theme viral 1010:1014 arg1 clearance 1016:1024 viral clearance 1010:1024 viral clearance of virus and CD8+ T cell distribution 1010:1062 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 7 81 theme NK 1347:1348 arg1 subset 1355:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset 1297:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection 1297:1399 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 0 82 theme NK 99:100 arg1 Cell 102:105 Hemagglutinin-Specific Memory NK Cell 69:105 Hemagglutinin-Specific Memory NK Cell 69:105 Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell. 33827945 5 83 theme signaling 887:895 arg1 pifithrin-μ 838:848 pifithrin-μ 838:848 pifithrin-μ 838:848 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 5 83 theme signaling 887:895 arg1 inhibitor 897:905 a p53-heat shock protein 70 (HSP70) signaling inhibitor 851:905 a p53-heat shock protein 70 (HSP70) signaling inhibitor 851:905 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 4 84 theme N-linked 512:519 arg1 sites 535:539 N-linked glycosylation sites 512:539 N-linked glycosylation sites on influenza hemagglutinin (HA) protein 512:579 These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. 33827945 5 85 theme gamma 737:741 arg1 IFN-γ 755:759 IFN-γ 755:759 IFN-γ 755:759 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 5 85 theme gamma 737:741 arg1 interferon 743:752 gamma interferon 737:752 gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor 737:905 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 5 86 theme NK 609:610 arg1 cells 612:616 memory-like NK cells 597:616 memory-like NK cells reported previously 597:636 Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-μ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. 33827945 6 87 theme infected 982:989 arg1 lung 991:994 infected lung 982:994 infected lung 982:994 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 8 88 theme same 1528:1531 arg1 antigen 1549:1555 the same influenza virus antigen 1524:1555 the same influenza virus antigen 1524:1555 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 6 89 dep virus 1029:1033 arg1 distribution 1051:1062 distribution 1051:1062 distribution 1051:1062 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 7 90 theme -specific 1323:1331 arg1 subset 1355:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset 1297:1360 a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection 1297:1399 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 4 91 theme NK 480:481 arg1 cells 483:487 These memory NK cells 467:487 These memory NK cells 467:487 These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. 33827945 7 92 theme memory 1167:1172 arg1 response 1174:1181 innate and adaptive immune memory response 1140:1181 innate and adaptive immune memory response 1140:1181 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 3 93 theme NK 376:377 arg1 subset 384:389 a novel mouse spleen NK cell subset 355:389 a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection 355:464 In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. 33827945 7 94 theme adaptive 1151:1158 arg1 response 1174:1181 innate and adaptive immune memory response 1140:1181 innate and adaptive immune memory response 1140:1181 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 1 95 theme Immune 108:113 arg1 memory 115:120 Immune memory 108:120 Immune memory 108:120 Immune memory represents the most efficient defense against invasion and transmission of infectious pathogens. 33827945 6 96 theme T 1044:1044 arg1 cell 1046:1049 CD8+ T cell 1039:1049 CD8+ T cell 1039:1049 During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. 33827945 3 97 theme mouse 363:367 arg1 subset 384:389 a novel mouse spleen NK cell subset 355:389 a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection 355:464 In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. 33827945 7 98 theme innate 1140:1145 arg1 response 1174:1181 innate and adaptive immune memory response 1140:1181 innate and adaptive immune memory response 1140:1181 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33827945 9 99 theme recall 1590:1595 arg1 responses 1597:1605 host recall responses 1585:1605 host recall responses 1585:1605 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 3 100 theme influenza 440:448 arg1 infection 456:464 intranasal influenza virus infection 429:464 intranasal influenza virus infection 429:464 In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. 33827945 4 101 from sites 535:539 arg1 protein 573:579 influenza hemagglutinin (HA) protein 544:579 influenza hemagglutinin (HA) protein 544:579 These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. 33827945 8 102 theme virus 1543:1547 arg1 antigen 1549:1555 the same influenza virus antigen 1524:1555 the same influenza virus antigen 1524:1555 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 4 103 theme influenza 544:552 arg1 HA 569:570 HA 569:570 HA 569:570 These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. 33827945 4 103 theme influenza 544:552 arg1 hemagglutinin 554:566 influenza hemagglutinin 544:566 influenza hemagglutinin (HA) protein 544:579 These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. 33827945 9 104 theme T 1615:1615 arg1 distribution 1622:1633 CD8 T cell distribution 1611:1633 CD8 T cell distribution 1611:1633 In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection. 33827945 8 105 theme memory 1408:1413 arg1 cells 1418:1422 These memory NK cells 1402:1422 These memory NK cells 1402:1422 These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. 33827945 7 106 theme recall 1240:1245 arg1 response.IMPORTANCE 1247:1265 recall response.IMPORTANCE 1240:1265 recall response.IMPORTANCE 1240:1265 This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. 33734437 7 0 theme N-linked 1269:1276 arg1 glycosylation 1286:1298 N-linked protein glycosylation 1269:1298 N-linked protein glycosylation in both female and male subjects 1269:1331 We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear. 33734437 3 1 theme glycans 766:772 arg1 glycans 766:772 the total plasma glycans 749:772 the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant 749:843 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 1 theme glycans 766:772 arg1 % 744:744 <0.3% 740:744 <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant 740:843 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 2 theme sensitive 528:536 arg1 assay 663:667 a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay 519:667 assay 663:667 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 3 dep 0.5 798:800 arg1 to 795:796 to 795:796 to 795:796 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 7 4 from glycosylation 1286:1298 arg1 subjects 1324:1331 both female and male subjects 1303:1331 both female and male subjects 1303:1331 We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear. 33734437 3 5 with females 806:812 arg1 variant 837:843 the p.(Asn107Ser) variant 819:843 the p.(Asn107Ser) variant 819:843 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 6 6 theme clinical 1133:1140 arg1 data 1142:1145 the molecular, biochemical, and clinical data 1101:1145 the molecular, biochemical, and clinical data for the 53 previously reported ALG13-CDG individuals 1101:1198 We also summarize the molecular, biochemical, and clinical data for the 53 previously reported ALG13-CDG individuals. 33734437 1 7 theme variable 274:281 arg1 phenotypes 292:301 variable clinical phenotypes 274:301 variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy 274:407 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 3 8 theme total 753:757 arg1 glycans 766:772 the total plasma glycans 749:772 the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant 749:843 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 4 9 theme abnormal 905:912 arg1 glycosylation 932:944 abnormal serum transferrin glycosylation 905:944 abnormal serum transferrin glycosylation 905:944 Among our 11 unrelated ALG13-CDG individuals, one male had abnormal serum transferrin glycosylation. 33734437 3 10 theme time-of-flight 607:620 arg1 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 10 theme time-of-flight 607:620 arg1 spectrometry 627:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry 539:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) 539:652 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 5 11 from variants 1018:1025 arg1 ALG13 1030:1034 ALG13 1030:1034 ALG13 1030:1034 We describe seven previously unreported subjects including three novel variants in ALG13 and report a milder neurodevelopmental course. 33734437 1 12 theme clinical 283:290 arg1 phenotypes 292:301 variable clinical phenotypes 274:301 variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy 274:407 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 0 13 theme expanded 82:89 arg1 phenotypes 91:100 expanded phenotypes 82:100 expanded phenotypes 82:100 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 33734437 1 14 theme epileptic 384:392 arg1 encephalopathy 394:407 epileptic encephalopathy 384:407 epileptic encephalopathy 384:407 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 0 15 link X-linked 6:13 arg1 disability 28:37 ALG13 X-linked intellectual disability 0:37 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 0:101 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 33734437 3 16 theme mass 622:625 arg1 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 16 theme mass 622:625 arg1 spectrometry 627:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry 539:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) 539:652 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 1 17 link X-linked 193:200 arg1 disorder 213:220 an X-linked congenital disorder 190:220 an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy 190:407 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 3 18 theme injection-electrospray 562:583 arg1 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 18 theme injection-electrospray 562:583 arg1 spectrometry 627:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry 539:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) 539:652 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 6 19 theme biochemical 1116:1126 arg1 data 1142:1145 the molecular, biochemical, and clinical data 1101:1145 the molecular, biochemical, and clinical data for the 53 previously reported ALG13-CDG individuals 1101:1198 We also summarize the molecular, biochemical, and clinical data for the 53 previously reported ALG13-CDG individuals. 33734437 2 20 theme de 433:434 arg1 c.3013C>T 441:449 a recurrent de novo c.3013C>T 421:449 a recurrent de novo c.3013C>T; p.(Asn107Ser) variant 421:472 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 4 21 theme unrelated 859:867 arg1 individuals 879:889 11 unrelated ALG13-CDG individuals 856:889 our 11 unrelated ALG13-CDG individuals 852:889 Among our 11 unrelated ALG13-CDG individuals, one male had abnormal serum transferrin glycosylation. 33734437 2 22 contain have 474:477 arg2 glycosylation 498:510 normal transferrin glycosylation 479:510 normal transferrin glycosylation 479:510 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 2 22 contain have 474:477 arg1 Girls 410:414 Girls 410:414 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant 410:472 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 3 23 theme ionization-quadrupole 585:605 arg1 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 23 theme ionization-quadrupole 585:605 arg1 spectrometry 627:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry 539:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) 539:652 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 24 from abnormalities 687:699 arg1 N-glycans 704:712 N-glycans 704:712 N-glycans 704:712 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 2 25 theme recurrent 423:431 arg1 c.3013C>T 441:449 a recurrent de novo c.3013C>T 421:449 a recurrent de novo c.3013C>T; p.(Asn107Ser) variant 421:472 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 0 26 theme X-linked 6:13 arg1 disability 28:37 ALG13 X-linked intellectual disability 0:37 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 0:101 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 33734437 7 27 theme protein 1278:1284 arg1 glycosylation 1286:1298 N-linked protein glycosylation 1269:1298 N-linked protein glycosylation in both female and male subjects 1269:1331 We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear. 33734437 7 28 theme underlying 1342:1351 arg1 mechanism 1353:1361 the underlying mechanism 1338:1361 the underlying mechanism 1338:1361 We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear. 33734437 7 29 theme male 1319:1322 arg1 subjects 1324:1331 both female and male subjects 1303:1331 both female and male subjects 1303:1331 We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear. 33734437 5 30 theme unreported 976:985 arg1 variants 1018:1025 three novel variants 1006:1025 three novel variants in ALG13 1006:1034 We describe seven previously unreported subjects including three novel variants in ALG13 and report a milder neurodevelopmental course. 33734437 5 30 theme unreported 976:985 arg1 subjects 987:994 seven previously unreported subjects 959:994 seven previously unreported subjects including three novel variants in ALG13 959:1034 We describe seven previously unreported subjects including three novel variants in ALG13 and report a milder neurodevelopmental course. 33734437 4 31 theme serum 914:918 arg1 glycosylation 932:944 abnormal serum transferrin glycosylation 905:944 abnormal serum transferrin glycosylation 905:944 Among our 11 unrelated ALG13-CDG individuals, one male had abnormal serum transferrin glycosylation. 33734437 1 32 theme X-linked 193:200 arg1 disorder 213:220 an X-linked congenital disorder 190:220 an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy 190:407 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 0 33 theme ALG13 0:4 arg1 disability 28:37 ALG13 X-linked intellectual disability 0:37 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 0:101 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 33734437 1 34 from variants 114:121 arg1 ALG13 126:130 ALG13 126:130 ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) 126:182 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 1 34 from variants 114:121 arg1 subunit 175:181 ALG13 UDP-N-acetylglucosaminyltransferase subunit 133:181 ALG13 UDP-N-acetylglucosaminyltransferase subunit 133:181 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 4 35 theme ALG13-CDG 869:877 arg1 individuals 879:889 11 unrelated ALG13-CDG individuals 856:889 our 11 unrelated ALG13-CDG individuals 852:889 Among our 11 unrelated ALG13-CDG individuals, one male had abnormal serum transferrin glycosylation. 33734437 3 36 theme p. 823:824 arg1 variant 837:843 the p.(Asn107Ser) variant 819:843 the p.(Asn107Ser) variant 819:843 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 1 37 theme congenital 202:211 arg1 disorder 213:220 an X-linked congenital disorder 190:220 an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy 190:407 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 2 38 theme Asn107Ser 455:463 arg1 variant 466:472 p.(Asn107Ser) variant 452:472 a recurrent de novo c.3013C>T; p.(Asn107Ser) variant 421:472 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 5 39 theme neurodevelopmental 1056:1073 arg1 course 1075:1080 a milder neurodevelopmental course 1047:1080 a milder neurodevelopmental course 1047:1080 We describe seven previously unreported subjects including three novel variants in ALG13 and report a milder neurodevelopmental course. 33734437 2 40 theme p. 452:453 arg1 variant 466:472 p.(Asn107Ser) variant 452:472 a recurrent de novo c.3013C>T; p.(Asn107Ser) variant 421:472 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 0 41 theme intellectual 15:26 arg1 disability 28:37 ALG13 X-linked intellectual disability 0:37 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 0:101 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 33734437 1 42 theme developmental 316:328 arg1 delay 330:334 developmental delay 316:334 developmental delay 316:334 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 1 43 theme Pathogenic 103:112 arg1 variants 114:121 Pathogenic variants 103:121 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) 103:182 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 3 44 theme semi-quantitative 539:555 arg1 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 44 theme semi-quantitative 539:555 arg1 spectrometry 627:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry 539:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) 539:652 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 0 45 theme New 40:42 arg1 variants 44:51 New variants 40:51 New variants 40:51 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 33734437 5 46 theme milder 1049:1054 arg1 course 1075:1080 a milder neurodevelopmental course 1047:1080 a milder neurodevelopmental course 1047:1080 We describe seven previously unreported subjects including three novel variants in ALG13 and report a milder neurodevelopmental course. 33734437 7 47 theme pathogenic 1232:1241 arg1 variants 1243:1250 ALG13 pathogenic variants 1226:1250 ALG13 pathogenic variants 1226:1250 We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear. 33734437 2 48 dep c.3013C>T 441:449 arg1 variant 466:472 p.(Asn107Ser) variant 452:472 a recurrent de novo c.3013C>T; p.(Asn107Ser) variant 421:472 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 1 49 theme glycosylation 225:237 arg1 disorder 213:220 an X-linked congenital disorder 190:220 an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy 190:407 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 2 50 theme transferrin 486:496 arg1 glycosylation 498:510 normal transferrin glycosylation 479:510 normal transferrin glycosylation 479:510 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 7 51 link N-linked 1269:1276 arg1 glycosylation 1286:1298 N-linked protein glycosylation 1269:1298 N-linked protein glycosylation in both female and male subjects 1269:1331 We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear. 33734437 2 52 theme normal 479:484 arg1 glycosylation 498:510 normal transferrin glycosylation 479:510 normal transferrin glycosylation 479:510 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 1 53 theme intellectual 337:348 arg1 disability 350:359 intellectual disability 337:359 intellectual disability 337:359 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 4 54 theme transferrin 920:930 arg1 glycosylation 932:944 abnormal serum transferrin glycosylation 905:944 abnormal serum transferrin glycosylation 905:944 Among our 11 unrelated ALG13-CDG individuals, one male had abnormal serum transferrin glycosylation. 33734437 3 55 theme N-glycan 654:661 arg1 assay 663:667 a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay 519:667 assay 663:667 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 6 56 theme ALG13-CDG 1178:1186 arg1 individuals 1188:1198 the 53 previously reported ALG13-CDG individuals 1151:1198 the 53 previously reported ALG13-CDG individuals 1151:1198 We also summarize the molecular, biochemical, and clinical data for the 53 previously reported ALG13-CDG individuals. 33734437 3 57 theme plasma 759:764 arg1 glycans 766:772 the total plasma glycans 749:772 the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant 749:843 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 7 58 theme female 1308:1313 arg1 subjects 1324:1331 both female and male subjects 1303:1331 both female and male subjects 1303:1331 We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear. 33734437 7 59 gly glycosylation 1286:1298 arg1 subjects 1324:1331 both female and male subjects 1303:1331 both female and male subjects 1303:1331 We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear. 33734437 6 60 theme reported 1169:1176 arg1 individuals 1188:1198 the 53 previously reported ALG13-CDG individuals 1151:1198 the 53 previously reported ALG13-CDG individuals 1151:1198 We also summarize the molecular, biochemical, and clinical data for the 53 previously reported ALG13-CDG individuals. 33734437 3 61 theme subtle 680:685 arg1 abnormalities 687:699 subtle abnormalities 680:699 subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant 680:843 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 0 62 dep disability 28:37 arg1 phenotypes 91:100 expanded phenotypes 82:100 expanded phenotypes 82:100 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 33734437 0 62 dep disability 28:37 arg1 variants 44:51 New variants 40:51 New variants 40:51 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 33734437 0 62 dep disability 28:37 arg1 analysis 68:75 glycosylation analysis 54:75 glycosylation analysis 54:75 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 33734437 2 63 with Girls 410:414 arg1 c.3013C>T 441:449 a recurrent de novo c.3013C>T 421:449 a recurrent de novo c.3013C>T; p.(Asn107Ser) variant 421:472 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 5 64 theme novel 1012:1016 arg1 variants 1018:1025 three novel variants 1006:1025 three novel variants in ALG13 1006:1034 We describe seven previously unreported subjects including three novel variants in ALG13 and report a milder neurodevelopmental course. 33734437 3 65 theme flow 557:560 arg1 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 65 theme flow 557:560 arg1 spectrometry 627:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry 539:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) 539:652 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 2 66 dep de 433:434 arg1 novo 436:439 novo 436:439 novo 436:439 Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. 33734437 6 67 theme molecular 1105:1113 arg1 data 1142:1145 the molecular, biochemical, and clinical data 1101:1145 the molecular, biochemical, and clinical data for the 53 previously reported ALG13-CDG individuals 1101:1198 We also summarize the molecular, biochemical, and clinical data for the 53 previously reported ALG13-CDG individuals. 33734437 1 68 theme ALG13 133:137 arg1 ALG13 126:130 ALG13 126:130 ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) 126:182 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 1 68 theme ALG13 133:137 arg1 subunit 175:181 ALG13 UDP-N-acetylglucosaminyltransferase subunit 133:181 ALG13 UDP-N-acetylglucosaminyltransferase subunit 133:181 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 3 69 dep assay 663:667 arg1 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 ESI-QTOF/MS 641:651 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 3 69 dep assay 663:667 arg1 spectrometry 627:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry 539:638 semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) 539:652 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33734437 0 70 theme glycosylation 54:66 arg1 analysis 68:75 glycosylation analysis 54:75 glycosylation analysis 54:75 ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. 33734437 1 71 theme infantile 362:370 arg1 spasms 372:377 infantile spasms 362:377 infantile spasms 362:377 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 1 72 contain have 269:272 arg2 phenotypes 292:301 variable clinical phenotypes 274:301 variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy 274:407 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 1 72 contain have 269:272 arg1 individuals 257:267 individuals 257:267 individuals 257:267 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 1 73 theme UDP-N-acetylglucosaminyltransferase 139:173 arg1 ALG13 126:130 ALG13 126:130 ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) 126:182 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 1 73 theme UDP-N-acetylglucosaminyltransferase 139:173 arg1 subunit 175:181 ALG13 UDP-N-acetylglucosaminyltransferase subunit 133:181 ALG13 UDP-N-acetylglucosaminyltransferase subunit 133:181 Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. 33734437 4 74 contain had 901:903 arg1 male 896:899 one male 892:899 one male 892:899 Among our 11 unrelated ALG13-CDG individuals, one male had abnormal serum transferrin glycosylation. 33734437 4 74 contain had 901:903 arg2 glycosylation 932:944 abnormal serum transferrin glycosylation 905:944 abnormal serum transferrin glycosylation 905:944 Among our 11 unrelated ALG13-CDG individuals, one male had abnormal serum transferrin glycosylation. 33734437 3 75 theme Asn107Ser 826:834 arg1 variant 837:843 the p.(Asn107Ser) variant 819:843 the p.(Asn107Ser) variant 819:843 Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. 33705408 6 0 theme fibrosis 1005:1012 arg1 likelihood 985:994 an increased likelihood 972:994 an increased likelihood of liver fibrosis 972:1012 Seven variants were associated with an increased likelihood of liver fibrosis. 33705408 2 1 theme pharmacological 309:323 arg1 intervention 325:336 pharmacological intervention 309:336 pharmacological intervention in coinfected patients 309:359 Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. 33705408 0 2 theme fibrosis 62:69 arg1 risk 71:74 increased liver fibrosis risk 46:74 increased liver fibrosis risk in HIV/HCV coinfected women 46:102 A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. 33705408 7 3 theme liver 1077:1081 arg1 fibrosis 1083:1090 liver fibrosis 1077:1090 liver fibrosis in HIV/HCV coinfected patients 1077:1121 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 3 4 from Study 458:462 arg1 data 398:401 clinical data 389:401 clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) 389:469 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 1 5 theme rapid 145:149 arg1 progression 166:176 more rapid liver fibrosis progression 140:176 more rapid liver fibrosis progression in hepatitis C (HCV) infection 140:207 HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. 33705408 7 6 theme rare 1155:1158 arg1 allele 1162:1167 the rare C allele 1151:1167 the rare C allele 1151:1167 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 7 7 dep 0.875 1217:1221 arg1 to 1214:1215 to 1214:1215 to 1214:1215 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 3 8 theme risk 487:490 arg1 factors 492:498 risk factors 487:498 risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis 487:589 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 4 9 theme non-synonymous 608:621 arg1 nsSNV 651:655 nsSNV 651:655 nsSNV 651:655 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 4 9 theme non-synonymous 608:621 arg1 variants 641:648 887 non-synonymous single nucleotide variants 604:648 887 non-synonymous single nucleotide variants (nsSNV) 604:656 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 4 10 theme coinfected 677:686 arg1 participants 688:699 661 coinfected participants 673:699 661 coinfected participants for genetic associations with changes in liver fibrosis risk 673:760 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 5 11 theme glycosylation 911:923 arg1 processes 925:933 glycosylation processes 911:933 glycosylation processes 911:933 The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. 33705408 4 12 theme genetic 705:711 arg1 associations 713:724 genetic associations 705:724 genetic associations with changes in liver fibrosis risk 705:760 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 5 13 theme amino 794:798 arg1 substitutions 805:817 amino acid substitutions 794:817 amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes 794:933 The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. 33705408 7 14 dep 1.144 1258:1262 arg1 to 1255:1256 to 1255:1256 to 1255:1256 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 1 15 theme liver 151:155 arg1 progression 166:176 more rapid liver fibrosis progression 140:176 more rapid liver fibrosis progression in hepatitis C (HCV) infection 140:207 HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. 33705408 0 16 theme coinfected 87:96 arg1 women 98:102 HIV/HCV coinfected women 79:102 HIV/HCV coinfected women 79:102 A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. 33705408 5 17 theme related 900:906 arg1 gene 895:898 a gene 893:898 a gene related to glycosylation processes 893:933 The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. 33705408 7 18 dep CI 1204:1205 arg1 0.875 1217:1221 0.334 to 0.875 1208:1221 0.334 to 0.875 1208:1221 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 1 19 theme fibrosis 157:164 arg1 progression 166:176 more rapid liver fibrosis progression 140:176 more rapid liver fibrosis progression in hepatitis C (HCV) infection 140:207 HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. 33705408 0 20 theme genomic 2:8 arg1 variant 10:16 A genomic variant 0:16 A genomic variant of ALPK2 0:25 A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. 33705408 8 21 theme disease 1437:1443 arg1 progression 1445:1455 liver disease progression 1431:1455 liver disease progression 1431:1455 Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression. 33705408 7 22 theme elevated 1179:1186 arg1 CI 1204:1205 0.61, 95% CI 1194:1205 CI 1204:1205 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 7 22 theme elevated 1179:1186 arg1 APRI 1188:1191 elevated APRI 1179:1191 elevated APRI (0.61, 95% CI, 0.334 to 0.875) 1179:1222 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 2 23 theme disease 273:279 arg1 outcomes 255:262 outcomes 255:262 outcomes of liver disease 255:279 Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. 33705408 4 24 theme nucleotide 630:639 arg1 nsSNV 651:655 nsSNV 651:655 nsSNV 651:655 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 4 24 theme nucleotide 630:639 arg1 variants 641:648 887 non-synonymous single nucleotide variants 604:648 887 non-synonymous single nucleotide variants (nsSNV) 604:656 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 7 25 theme homozygous 1136:1145 arg1 individuals 1124:1134 individuals 1124:1134 individuals homozygous for the rare C allele 1124:1167 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 8 26 theme liver 1431:1435 arg1 progression 1445:1455 liver disease progression 1431:1455 liver disease progression 1431:1455 Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression. 33705408 7 27 theme ALPK2 1040:1044 arg1 rs3809973 1046:1054 ALPK2 rs3809973 1040:1054 ALPK2 rs3809973 1040:1054 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 7 27 theme ALPK2 1040:1044 arg1 variant 1031:1037 The most common variant 1015:1037 The most common variant 1015:1037 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 2 28 theme liver 267:271 arg1 disease 273:279 liver disease 267:279 liver disease 267:279 Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. 33705408 2 29 theme coinfected 341:350 arg1 patients 352:359 coinfected patients 341:359 coinfected patients 341:359 Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. 33705408 3 30 theme surrogate 546:554 arg1 measurements 556:567 FIB-4 surrogate measurements 540:567 FIB-4 surrogate measurements 540:567 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 7 31 theme common 1024:1029 arg1 rs3809973 1046:1054 ALPK2 rs3809973 1040:1054 ALPK2 rs3809973 1040:1054 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 7 31 theme common 1024:1029 arg1 variant 1031:1037 The most common variant 1015:1037 The most common variant 1015:1037 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 2 32 from intervention 325:336 arg1 patients 352:359 coinfected patients 341:359 coinfected patients 341:359 Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. 33705408 6 33 theme liver 999:1003 arg1 fibrosis 1005:1012 liver fibrosis 999:1012 liver fibrosis 999:1012 Seven variants were associated with an increased likelihood of liver fibrosis. 33705408 4 34 from changes 731:737 arg1 risk 757:760 liver fibrosis risk 742:760 liver fibrosis risk 742:760 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 1 35 theme hepatitis 181:189 arg1 infection 199:207 hepatitis C (HCV) infection 181:207 hepatitis C (HCV) infection 181:207 HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. 33705408 7 36 theme coinfected 1283:1292 arg1 women 1294:1298 those coinfected women 1277:1298 those coinfected women without the variant 1277:1318 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 4 37 with associations 713:724 arg1 changes 731:737 changes 731:737 changes in liver fibrosis risk 731:760 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 0 38 from risk 71:74 arg1 women 98:102 HIV/HCV coinfected women 79:102 HIV/HCV coinfected women 79:102 A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. 33705408 4 39 theme participants 688:699 arg1 subset 663:668 a subset 661:668 a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk 661:760 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 1 40 theme C 191:191 arg1 infection 199:207 hepatitis C (HCV) infection 181:207 hepatitis C (HCV) infection 181:207 HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. 33705408 3 41 theme HIV 454:456 arg1 WIHS 465:468 WIHS 465:468 WIHS 465:468 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 3 41 theme HIV 454:456 arg1 Study 458:462 the Women's Interagency HIV Study 430:462 the Women's Interagency HIV Study (WIHS) 430:469 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 5 42 link N-linked 842:849 arg1 NxS/T 866:870 NxS/T 866:870 NxS/T 866:870 The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. 33705408 5 42 link N-linked 842:849 arg1 glycosylation 851:863 N-linked glycosylation 842:863 an N-linked glycosylation (NxS/T) sequon 839:878 The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. 33705408 5 43 theme acid 800:803 arg1 substitutions 805:817 amino acid substitutions 794:817 amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes 794:933 The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. 33705408 3 44 theme clinical 389:396 arg1 data 398:401 clinical data 389:401 clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) 389:469 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 3 45 theme 1,858 406:410 arg1 participants 412:423 1,858 participants 406:423 1,858 participants 406:423 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 0 46 theme ALPK2 21:25 arg1 variant 10:16 A genomic variant 0:16 A genomic variant of ALPK2 0:25 A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. 33705408 7 47 theme coinfected 1103:1112 arg1 patients 1114:1121 HIV/HCV coinfected patients 1095:1121 HIV/HCV coinfected patients 1095:1121 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 3 48 theme FIB-4 540:544 arg1 measurements 556:567 FIB-4 surrogate measurements 540:567 FIB-4 surrogate measurements 540:567 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 1 49 theme HCV 194:196 arg1 infection 199:207 hepatitis C (HCV) infection 181:207 hepatitis C (HCV) infection 181:207 HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. 33705408 5 50 gly glycosylation 851:863 arg2 sequon 873:878 an N-linked glycosylation (NxS/T) sequon 839:878 an N-linked glycosylation (NxS/T) sequon 839:878 The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. 33705408 7 51 dep 0.74 1235:1238 arg1 1.144 1258:1262 1.144 1258:1262 1.144 1258:1262 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 7 51 dep 0.74 1235:1238 arg1 % 1243:1243 95% CI 1241:1246 95% CI 1241:1246 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 3 52 theme Interagency 442:452 arg1 WIHS 465:468 WIHS 465:468 WIHS 465:468 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 3 52 theme Interagency 442:452 arg1 Study 458:462 the Women's Interagency HIV Study 430:462 the Women's Interagency HIV Study (WIHS) 430:469 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 8 53 theme ALPK2 1354:1358 arg1 rs3809973 1360:1368 ALPK2 rs3809973 1354:1368 ALPK2 rs3809973 1354:1368 Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression. 33705408 1 54 theme HIV 105:107 arg1 coinfection 109:119 HIV coinfection 105:119 HIV coinfection 105:119 HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. 33705408 4 55 theme single 623:628 arg1 nsSNV 651:655 nsSNV 651:655 nsSNV 651:655 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 4 55 theme single 623:628 arg1 variants 641:648 887 non-synonymous single nucleotide variants 604:648 887 non-synonymous single nucleotide variants (nsSNV) 604:656 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 4 56 theme liver 742:746 arg1 risk 757:760 liver fibrosis risk 742:760 liver fibrosis risk 742:760 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 7 57 theme % 1202:1202 arg1 CI 1204:1205 0.61, 95% CI 1194:1205 CI 1204:1205 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 7 57 theme % 1202:1202 arg1 APRI 1188:1191 elevated APRI 1179:1191 elevated APRI (0.61, 95% CI, 0.334 to 0.875) 1179:1222 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 7 58 theme 0.334 1208:1212 arg1 0.875 1217:1221 0.334 to 0.875 1208:1221 0.334 to 0.875 1208:1221 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 3 59 theme advanced 573:580 arg1 fibrosis 582:589 advanced fibrosis 573:589 advanced fibrosis 573:589 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 1 60 from progression 166:176 arg1 infection 199:207 hepatitis C (HCV) infection 181:207 hepatitis C (HCV) infection 181:207 HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. 33705408 3 61 from changes 516:522 arg1 measurements 556:567 FIB-4 surrogate measurements 540:567 FIB-4 surrogate measurements 540:567 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 3 61 from changes 516:522 arg1 APRI 531:534 APRI 531:534 APRI 531:534 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 6 62 theme increased 975:983 arg1 likelihood 985:994 an increased likelihood 972:994 an increased likelihood of liver fibrosis 972:1012 Seven variants were associated with an increased likelihood of liver fibrosis. 33705408 0 63 theme liver 56:60 arg1 risk 71:74 increased liver fibrosis risk 46:74 increased liver fibrosis risk in HIV/HCV coinfected women 46:102 A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. 33705408 3 64 theme participants 412:423 arg1 data 398:401 clinical data 389:401 clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) 389:469 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 2 65 theme much 220:223 arg1 work 225:228 much work 220:228 much work 220:228 Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. 33705408 8 66 theme increased 1412:1420 arg1 risk 1422:1425 increased risk 1412:1425 increased risk for liver disease progression 1412:1455 Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression. 33705408 5 67 theme N-linked 842:849 arg1 NxS/T 866:870 NxS/T 866:870 NxS/T 866:870 The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. 33705408 5 67 theme N-linked 842:849 arg1 glycosylation 851:863 N-linked glycosylation 842:863 an N-linked glycosylation (NxS/T) sequon 839:878 The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. 33705408 3 68 dep APRI 531:534 arg1 the 527:529 the 527:529 the 527:529 In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. 33705408 0 69 theme increased 46:54 arg1 risk 71:74 increased liver fibrosis risk 46:74 increased liver fibrosis risk in HIV/HCV coinfected women 46:102 A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. 33705408 7 70 from fibrosis 1083:1090 arg1 patients 1114:1121 HIV/HCV coinfected patients 1095:1121 HIV/HCV coinfected patients 1095:1121 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 33705408 4 71 theme fibrosis 748:755 arg1 risk 757:760 liver fibrosis risk 742:760 liver fibrosis risk 742:760 We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. 33705408 5 72 theme glycosylation 851:863 arg1 sequon 873:878 an N-linked glycosylation (NxS/T) sequon 839:878 an N-linked glycosylation (NxS/T) sequon 839:878 The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. 33705408 7 73 theme C 1160:1160 arg1 allele 1162:1167 the rare C allele 1151:1167 the rare C allele 1151:1167 The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. 35676476 1 0 from pathogens 198:206 arg1 environment 229:239 the extracellular environment 211:239 the extracellular environment 211:239 Adaptive immune components are thought to exert non-overlapping roles in antimicrobial host defence, with antibodies targeting pathogens in the extracellular environment and T cells eliminating infection inside cells1,2. 35676476 6 1 theme B 1287:1287 arg1 cells 1289:1293 B cells 1287:1293 B cells leading to antibody-mediated protection 1287:1333 Deacetylated L. monocytogenes-specific IgG protected neonates through the sialic acid receptor CD226,7, which suppressed IL-10 production by B cells leading to antibody-mediated protection. 35676476 4 2 theme monocytogenes-specific 718:739 arg1 IgG 741:743 L. monocytogenes-specific IgG 715:743 L. monocytogenes-specific IgG 715:743 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 5 3 theme variable-region 1112:1126 arg1 glycans 1137:1143 IgG variable-region N-linked glycans 1108:1143 IgG variable-region N-linked glycans 1108:1143 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 4 4 from mice 823:826 arg1 transfer 762:769 passive transfer 754:769 passive transfer of antibodies from primed pregnant, but not virgin, mice 754:826 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 4 5 theme L. 715:716 arg1 IgG 741:743 L. monocytogenes-specific IgG 715:743 L. monocytogenes-specific IgG 715:743 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 2 6 theme transferred 330:340 arg1 immunity 342:349 vertically transferred immunity 319:349 vertically transferred immunity from mothers to babies 319:372 Reliance on antibodies for vertically transferred immunity from mothers to babies may explain neonatal susceptibility to intracellular infections3,4. 35676476 2 7 from mothers 356:362 arg1 immunity 342:349 vertically transferred immunity 319:349 vertically transferred immunity from mothers to babies 319:372 Reliance on antibodies for vertically transferred immunity from mothers to babies may explain neonatal susceptibility to intracellular infections3,4. 35676476 6 8 theme monocytogenes-specific 1162:1183 arg1 IgG 1185:1187 Deacetylated L. monocytogenes-specific IgG 1146:1187 Deacetylated L. monocytogenes-specific IgG 1146:1187 Deacetylated L. monocytogenes-specific IgG protected neonates through the sialic acid receptor CD226,7, which suppressed IL-10 production by B cells leading to antibody-mediated protection. 35676476 7 9 theme protective 1416:1425 arg1 roles 1427:1431 protective roles 1416:1431 protective roles for antibodies against intracellular infection and fine-tuned adaptations 1416:1505 Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life. 35676476 1 10 theme immune 80:85 arg1 components 87:96 Adaptive immune components 71:96 Adaptive immune components 71:96 Adaptive immune components are thought to exert non-overlapping roles in antimicrobial host defence, with antibodies targeting pathogens in the extracellular environment and T cells eliminating infection inside cells1,2. 35676476 5 11 theme acetyl 1043:1048 arg1 esterase5 1050:1058 sialic acid acetyl esterase5 1031:1058 sialic acid acetyl esterase5 1031:1058 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 5 12 theme acid 1091:1094 arg1 residues 1096:1103 terminal sialic acid residues 1075:1103 terminal sialic acid residues on IgG variable-region N-linked glycans 1075:1143 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 5 13 link N-linked 1128:1135 arg1 glycans 1137:1143 IgG variable-region N-linked glycans 1108:1143 IgG variable-region N-linked glycans 1108:1143 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 5 14 theme protective 987:996 arg1 function 998:1005 protective function 987:1005 protective function 987:1005 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 4 15 theme antibodies 774:783 arg1 transfer 762:769 passive transfer 754:769 passive transfer of antibodies from primed pregnant, but not virgin, mice 754:826 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 6 16 theme sialic 1220:1225 arg1 receptor 1232:1239 the sialic acid receptor CD226,7 1216:1247 the sialic acid receptor CD226,7 1216:1247 Deacetylated L. monocytogenes-specific IgG protected neonates through the sialic acid receptor CD226,7, which suppressed IL-10 production by B cells leading to antibody-mediated protection. 35676476 5 17 theme sialic 1084:1089 arg1 residues 1096:1103 terminal sialic acid residues 1075:1103 terminal sialic acid residues on IgG variable-region N-linked glycans 1075:1143 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 6 18 theme L. 1159:1160 arg1 IgG 1185:1187 Deacetylated L. monocytogenes-specific IgG 1146:1187 Deacetylated L. monocytogenes-specific IgG 1146:1187 Deacetylated L. monocytogenes-specific IgG protected neonates through the sialic acid receptor CD226,7, which suppressed IL-10 production by B cells leading to antibody-mediated protection. 35676476 4 19 theme Infection 610:618 arg1 susceptibility 620:633 Infection susceptibility 610:633 Infection susceptibility 610:633 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 0 20 theme intracellular 46:58 arg1 infection 60:68 intracellular infection 46:68 intracellular infection 46:68 Pregnancy enables antibody protection against intracellular infection. 35676476 6 21 theme IL-10 1267:1271 arg1 production 1273:1282 IL-10 production 1267:1282 IL-10 production 1267:1282 Deacetylated L. monocytogenes-specific IgG protected neonates through the sialic acid receptor CD226,7, which suppressed IL-10 production by B cells leading to antibody-mediated protection. 35676476 5 22 theme transferred 913:923 arg1 protection 925:934 vertically transferred protection 902:934 vertically transferred protection 902:934 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 6 23 theme Deacetylated 1146:1157 arg1 IgG 1185:1187 Deacetylated L. monocytogenes-specific IgG 1146:1187 Deacetylated L. monocytogenes-specific IgG 1146:1187 Deacetylated L. monocytogenes-specific IgG protected neonates through the sialic acid receptor CD226,7, which suppressed IL-10 production by B cells leading to antibody-mediated protection. 35676476 4 24 theme virgin 815:820 arg1 mice 823:826 primed pregnant, but not virgin, mice 790:826 primed pregnant, but not virgin, mice 790:826 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 7 25 theme joined 1382:1387 arg1 unit 1403:1406 a joined immunological unit 1380:1406 a joined immunological unit 1380:1406 Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life. 35676476 4 26 theme primed 689:694 arg1 mothers 696:702 preconceptually primed mothers 673:702 preconceptually primed mothers possessing L. monocytogenes-specific IgG 673:743 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 4 27 contain possessing 704:713 arg1 mothers 696:702 preconceptually primed mothers 673:702 preconceptually primed mothers possessing L. monocytogenes-specific IgG 673:743 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 4 27 contain possessing 704:713 arg2 IgG 741:743 L. monocytogenes-specific IgG 715:743 L. monocytogenes-specific IgG 715:743 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 5 28 theme sialic 1031:1036 arg1 acid 1038:1041 sialic acid 1031:1041 sialic acid acetyl esterase5 1031:1058 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 5 29 theme antibody 963:970 arg1 acquisition 972:982 antibody acquisition 963:982 antibody acquisition 963:982 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 5 30 theme maternal 838:845 arg1 cells 849:853 maternal B cells 838:853 maternal B cells 838:853 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 5 31 theme IgG 1108:1110 arg1 glycans 1137:1143 IgG variable-region N-linked glycans 1108:1143 IgG variable-region N-linked glycans 1108:1143 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 3 32 theme intracellular 563:575 arg1 monocytogenes 595:607 the prototypical intracellular pathogen Listeria monocytogenes 546:607 the prototypical intracellular pathogen Listeria monocytogenes 546:607 Here we show that pregnancy-induced post-translational antibody modification enables protection against the prototypical intracellular pathogen Listeria monocytogenes. 35676476 0 33 theme antibody 18:25 arg1 protection 27:36 antibody protection 18:36 antibody protection against intracellular infection 18:68 Pregnancy enables antibody protection against intracellular infection. 35676476 5 34 theme B 847:847 arg1 cells 849:853 maternal B cells 838:853 maternal B cells 838:853 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 1 35 theme non-overlapping 119:133 arg1 roles 135:139 non-overlapping roles 119:139 non-overlapping roles 119:139 Adaptive immune components are thought to exert non-overlapping roles in antimicrobial host defence, with antibodies targeting pathogens in the extracellular environment and T cells eliminating infection inside cells1,2. 35676476 3 36 theme pathogen 577:584 arg1 monocytogenes 595:607 the prototypical intracellular pathogen Listeria monocytogenes 546:607 the prototypical intracellular pathogen Listeria monocytogenes 546:607 Here we show that pregnancy-induced post-translational antibody modification enables protection against the prototypical intracellular pathogen Listeria monocytogenes. 35676476 3 37 theme post-translational 478:495 arg1 modification 506:517 pregnancy-induced post-translational antibody modification 460:517 pregnancy-induced post-translational antibody modification 460:517 Here we show that pregnancy-induced post-translational antibody modification enables protection against the prototypical intracellular pathogen Listeria monocytogenes. 35676476 5 38 theme N-linked 1128:1135 arg1 glycans 1137:1143 IgG variable-region N-linked glycans 1108:1143 IgG variable-region N-linked glycans 1108:1143 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 5 39 theme function 998:1005 arg1 acquisition 972:982 antibody acquisition 963:982 antibody acquisition 963:982 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 4 40 theme primed 790:795 arg1 mice 823:826 primed pregnant, but not virgin, mice 790:826 primed pregnant, but not virgin, mice 790:826 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 2 41 from Reliance 292:299 arg1 antibodies 304:313 antibodies 304:313 antibodies 304:313 Reliance on antibodies for vertically transferred immunity from mothers to babies may explain neonatal susceptibility to intracellular infections3,4. 35676476 4 42 theme pregnant 797:804 arg1 mice 823:826 primed pregnant, but not virgin, mice 790:826 primed pregnant, but not virgin, mice 790:826 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 3 43 theme antibody 497:504 arg1 modification 506:517 pregnancy-induced post-translational antibody modification 460:517 pregnancy-induced post-translational antibody modification 460:517 Here we show that pregnancy-induced post-translational antibody modification enables protection against the prototypical intracellular pathogen Listeria monocytogenes. 35676476 7 44 theme maternal-fetal 1357:1370 arg1 dyad 1372:1375 the maternal-fetal dyad 1353:1375 the maternal-fetal dyad 1353:1375 Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life. 35676476 7 45 theme early 1552:1556 arg1 life 1558:1561 early life 1552:1561 early life 1552:1561 Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life. 35676476 7 46 theme dyad 1372:1375 arg1 Consideration 1336:1348 Consideration 1336:1348 Consideration of the maternal-fetal dyad as a joined immunological unit 1336:1406 Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life. 35676476 3 47 theme prototypical 550:561 arg1 monocytogenes 595:607 the prototypical intracellular pathogen Listeria monocytogenes 546:607 the prototypical intracellular pathogen Listeria monocytogenes 546:607 Here we show that pregnancy-induced post-translational antibody modification enables protection against the prototypical intracellular pathogen Listeria monocytogenes. 35676476 4 48 theme neonatal 651:658 arg1 mice 660:663 neonatal mice 651:663 neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG 651:743 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 6 49 theme acid 1227:1230 arg1 receptor 1232:1239 the sialic acid receptor CD226,7 1216:1247 the sialic acid receptor CD226,7 1216:1247 Deacetylated L. monocytogenes-specific IgG protected neonates through the sialic acid receptor CD226,7, which suppressed IL-10 production by B cells leading to antibody-mediated protection. 35676476 6 50 theme antibody-mediated 1306:1322 arg1 protection 1324:1333 antibody-mediated protection 1306:1333 antibody-mediated protection 1306:1333 Deacetylated L. monocytogenes-specific IgG protected neonates through the sialic acid receptor CD226,7, which suppressed IL-10 production by B cells leading to antibody-mediated protection. 35676476 2 51 theme neonatal 386:393 arg1 susceptibility 395:408 neonatal susceptibility 386:408 neonatal susceptibility to intracellular infections3,4 386:439 Reliance on antibodies for vertically transferred immunity from mothers to babies may explain neonatal susceptibility to intracellular infections3,4. 35676476 3 52 theme pregnancy-induced 460:476 arg1 modification 506:517 pregnancy-induced post-translational antibody modification 460:517 pregnancy-induced post-translational antibody modification 460:517 Here we show that pregnancy-induced post-translational antibody modification enables protection against the prototypical intracellular pathogen Listeria monocytogenes. 35676476 5 53 theme terminal 1075:1082 arg1 residues 1096:1103 terminal sialic acid residues 1075:1103 terminal sialic acid residues on IgG variable-region N-linked glycans 1075:1143 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 7 54 theme fine-tuned 1484:1493 arg1 adaptations 1495:1505 fine-tuned adaptations 1484:1505 fine-tuned adaptations 1484:1505 Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life. 35676476 1 55 theme antimicrobial 144:156 arg1 defence 163:169 antimicrobial host defence 144:169 antimicrobial host defence 144:169 Adaptive immune components are thought to exert non-overlapping roles in antimicrobial host defence, with antibodies targeting pathogens in the extracellular environment and T cells eliminating infection inside cells1,2. 35676476 4 56 theme passive 754:760 arg1 transfer 762:769 passive transfer 754:769 passive transfer of antibodies from primed pregnant, but not virgin, mice 754:826 Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. 35676476 1 57 theme Adaptive 71:78 arg1 components 87:96 Adaptive immune components 71:96 Adaptive immune components 71:96 Adaptive immune components are thought to exert non-overlapping roles in antimicrobial host defence, with antibodies targeting pathogens in the extracellular environment and T cells eliminating infection inside cells1,2. 35676476 1 58 theme host 158:161 arg1 defence 163:169 antimicrobial host defence 144:169 antimicrobial host defence 144:169 Adaptive immune components are thought to exert non-overlapping roles in antimicrobial host defence, with antibodies targeting pathogens in the extracellular environment and T cells eliminating infection inside cells1,2. 35676476 5 59 from residues 1096:1103 arg1 glycans 1137:1143 IgG variable-region N-linked glycans 1108:1143 IgG variable-region N-linked glycans 1108:1143 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 3 60 theme Listeria 586:593 arg1 monocytogenes 595:607 the prototypical intracellular pathogen Listeria monocytogenes 546:607 the prototypical intracellular pathogen Listeria monocytogenes 546:607 Here we show that pregnancy-induced post-translational antibody modification enables protection against the prototypical intracellular pathogen Listeria monocytogenes. 35676476 1 61 theme T 245:245 arg1 cells 247:251 T cells 245:251 T cells eliminating infection 245:273 Adaptive immune components are thought to exert non-overlapping roles in antimicrobial host defence, with antibodies targeting pathogens in the extracellular environment and T cells eliminating infection inside cells1,2. 35676476 1 62 theme extracellular 215:227 arg1 environment 229:239 the extracellular environment 211:239 the extracellular environment 211:239 Adaptive immune components are thought to exert non-overlapping roles in antimicrobial host defence, with antibodies targeting pathogens in the extracellular environment and T cells eliminating infection inside cells1,2. 35676476 5 63 theme acid 1038:1041 arg1 esterase5 1050:1058 sialic acid acetyl esterase5 1031:1058 sialic acid acetyl esterase5 1031:1058 Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. 35676476 7 64 theme immunological 1389:1401 arg1 unit 1403:1406 a joined immunological unit 1380:1406 a joined immunological unit 1380:1406 Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life. 35676476 7 65 theme host 1518:1521 arg1 defence 1523:1529 host defence 1518:1529 host defence 1518:1529 Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life. 35676476 2 66 theme intracellular 413:425 arg1 infections3,4 427:439 intracellular infections3,4 413:439 intracellular infections3,4 413:439 Reliance on antibodies for vertically transferred immunity from mothers to babies may explain neonatal susceptibility to intracellular infections3,4. 35676476 7 67 theme intracellular 1456:1468 arg1 infection 1470:1478 intracellular infection 1456:1478 intracellular infection 1456:1478 Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life. 8404898 7 0 theme human 1021:1025 arg1 lipase 1058:1063 the human pancreatic bile-salt-dependent lipase 1017:1063 the human pancreatic bile-salt-dependent lipase 1017:1063 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 1 1 theme bile-salt-dependent 168:186 arg1 lipase 188:193 bile-salt-dependent lipase 168:193 bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor 168:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 6 2 theme N-acetyllactosamine 921:939 arg1 repeats 941:947 no linear N-acetyllactosamine repeats 911:947 no linear N-acetyllactosamine repeats 911:947 Most of these structures have no linear N-acetyllactosamine repeats. 8404898 0 3 link N-linked 17:24 arg1 oligosaccharides 26:41 N-linked oligosaccharides 17:41 N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase 17:88 The structure of N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase. 8404898 1 4 theme lipase 188:193 arg1 chains 158:163 the N-linked oligosaccharide chains 129:163 the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor 129:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 4 5 theme Fucose 627:632 arg1 residues 634:641 Fucose residues 627:641 Fucose residues 627:641 Fucose residues were identified for some trimannosyl core structures and were alpha(1-6) or alpha(1-2) linked to the innermost GlcNAc residue and a terminal Gal residue, respectively. 8404898 7 6 contain possess 1065:1071 arg1 chains 1007:1012 the sugar chains 997:1012 the sugar chains of the human pancreatic bile-salt-dependent lipase 997:1063 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 7 6 contain possess 1065:1071 arg2 determinant 1105:1115 a blood-group-related antigenic determinant 1073:1115 a blood-group-related antigenic determinant 1073:1115 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 2 7 theme acidic 312:317 arg1 chains 319:324 acidic chains 312:324 acidic chains 312:324 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 3 8 theme complex 613:619 arg1 type 621:624 the biantennary complex type 597:624 the biantennary complex type 597:624 Structural analysis was performed by means of sequential glycosidase digestion and revealed that the neutral sugar chains are mainly of the biantennary complex type. 8404898 2 9 with filtration 449:458 arg1 lectins 425:431 immobilized lectins 413:431 immobilized lectins 413:431 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 4 10 theme terminal 775:782 arg1 residue 788:794 a terminal Gal residue 773:794 a terminal Gal residue 773:794 Fucose residues were identified for some trimannosyl core structures and were alpha(1-6) or alpha(1-2) linked to the innermost GlcNAc residue and a terminal Gal residue, respectively. 8404898 2 11 theme column 386:391 arg1 chromatography 393:406 serial column chromatography 379:406 serial column chromatography with immobilized lectins 379:431 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 6 12 theme linear 914:919 arg1 repeats 941:947 no linear N-acetyllactosamine repeats 911:947 no linear N-acetyllactosamine repeats 911:947 Most of these structures have no linear N-acetyllactosamine repeats. 8404898 5 13 theme oligosaccharide 853:867 arg1 structures 869:878 the oligosaccharide structures 849:878 the oligosaccharide structures 849:878 Sialyl residues were also involved in the oligosaccharide structures. 8404898 3 14 theme glycosidase 518:528 arg1 digestion 530:538 sequential glycosidase digestion 507:538 sequential glycosidase digestion 507:538 Structural analysis was performed by means of sequential glycosidase digestion and revealed that the neutral sugar chains are mainly of the biantennary complex type. 8404898 2 15 theme Bio-Gel 437:443 arg1 filtration 449:458 Bio-Gel P-4 filtration 437:458 Bio-Gel P-4 filtration 437:458 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 7 16 theme bile-salt-dependent 1038:1056 arg1 lipase 1058:1063 the human pancreatic bile-salt-dependent lipase 1017:1063 the human pancreatic bile-salt-dependent lipase 1017:1063 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 2 17 with chromatography 393:406 arg1 lectins 425:431 immobilized lectins 413:431 immobilized lectins 413:431 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 7 18 theme several 964:970 arg1 approaches 972:981 several approaches 964:981 several approaches 964:981 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 2 19 theme paper 329:333 arg1 electrophoresis 335:349 paper electrophoresis 329:349 paper electrophoresis 329:349 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 4 20 theme Gal 784:786 arg1 residue 788:794 a terminal Gal residue 773:794 a terminal Gal residue 773:794 Fucose residues were identified for some trimannosyl core structures and were alpha(1-6) or alpha(1-2) linked to the innermost GlcNAc residue and a terminal Gal residue, respectively. 8404898 1 21 theme pancreatic 213:222 arg1 juice 224:228 the pancreatic juice 209:228 the pancreatic juice of a normal donor 209:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 0 22 theme N-linked 17:24 arg1 oligosaccharides 26:41 N-linked oligosaccharides 17:41 N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase 17:88 The structure of N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase. 8404898 7 23 theme sugar 1001:1005 arg1 chains 1007:1012 the sugar chains 997:1012 the sugar chains of the human pancreatic bile-salt-dependent lipase 997:1063 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 3 24 theme biantennary 601:611 arg1 type 621:624 the biantennary complex type 597:624 the biantennary complex type 597:624 Structural analysis was performed by means of sequential glycosidase digestion and revealed that the neutral sugar chains are mainly of the biantennary complex type. 8404898 3 25 theme sequential 507:516 arg1 digestion 530:538 sequential glycosidase digestion 507:538 sequential glycosidase digestion 507:538 Structural analysis was performed by means of sequential glycosidase digestion and revealed that the neutral sugar chains are mainly of the biantennary complex type. 8404898 4 26 theme GlcNAc 754:759 arg1 residue 761:767 the innermost GlcNAc residue 740:767 the innermost GlcNAc residue 740:767 Fucose residues were identified for some trimannosyl core structures and were alpha(1-6) or alpha(1-2) linked to the innermost GlcNAc residue and a terminal Gal residue, respectively. 8404898 7 27 theme lipase 1058:1063 arg1 chains 1007:1012 the sugar chains 997:1012 the sugar chains of the human pancreatic bile-salt-dependent lipase 997:1063 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 2 28 theme serial 379:384 arg1 chromatography 393:406 serial column chromatography 379:406 serial column chromatography with immobilized lectins 379:431 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 3 29 theme sugar 570:574 arg1 chains 576:581 the neutral sugar chains 558:581 the neutral sugar chains 558:581 Structural analysis was performed by means of sequential glycosidase digestion and revealed that the neutral sugar chains are mainly of the biantennary complex type. 8404898 1 30 attach isolated 195:202 arg2 lipase 188:193 bile-salt-dependent lipase 168:193 bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor 168:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 1 30 attach isolated 195:202 arg1 juice 224:228 the pancreatic juice 209:228 the pancreatic juice of a normal donor 209:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 2 31 theme immobilized 413:423 arg1 lectins 425:431 immobilized lectins 413:431 immobilized lectins 413:431 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 0 32 theme oligosaccharides 26:41 arg1 structure 4:12 The structure 0:12 The structure of N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase 0:88 The structure of N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase. 8404898 3 33 theme Structural 461:470 arg1 analysis 472:479 Structural analysis 461:479 Structural analysis 461:479 Structural analysis was performed by means of sequential glycosidase digestion and revealed that the neutral sugar chains are mainly of the biantennary complex type. 8404898 1 34 theme normal 235:240 arg1 donor 242:246 a normal donor 233:246 a normal donor 233:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 0 35 theme pancreatic 52:61 arg1 lipase 83:88 human pancreatic bile-salt-dependent lipase 46:88 human pancreatic bile-salt-dependent lipase 46:88 The structure of N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase. 8404898 1 36 link N-linked 133:140 arg1 chains 158:163 the N-linked oligosaccharide chains 129:163 the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor 129:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 7 37 theme blood-group-related 1075:1093 arg1 determinant 1105:1115 a blood-group-related antigenic determinant 1073:1115 a blood-group-related antigenic determinant 1073:1115 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 0 38 theme human 46:50 arg1 lipase 83:88 human pancreatic bile-salt-dependent lipase 46:88 human pancreatic bile-salt-dependent lipase 46:88 The structure of N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase. 8404898 3 39 theme neutral 562:568 arg1 chains 576:581 the neutral sugar chains 558:581 the neutral sugar chains 558:581 Structural analysis was performed by means of sequential glycosidase digestion and revealed that the neutral sugar chains are mainly of the biantennary complex type. 8404898 7 40 from approaches 972:981 arg1 Evidence 950:957 Evidence 950:957 Evidence from several approaches 950:981 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 7 41 theme antigenic 1095:1103 arg1 determinant 1105:1115 a blood-group-related antigenic determinant 1073:1115 a blood-group-related antigenic determinant 1073:1115 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 5 42 theme Sialyl 811:816 arg1 residues 818:825 Sialyl residues 811:825 Sialyl residues 811:825 Sialyl residues were also involved in the oligosaccharide structures. 8404898 1 43 theme N-linked 133:140 arg1 chains 158:163 the N-linked oligosaccharide chains 129:163 the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor 129:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 1 44 theme donor 242:246 arg1 juice 224:228 the pancreatic juice 209:228 the pancreatic juice of a normal donor 209:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 2 45 theme sugar 279:283 arg1 chains 285:290 neutral sugar chains 271:290 neutral sugar chains 271:290 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 7 46 theme pancreatic 1027:1036 arg1 lipase 1058:1063 the human pancreatic bile-salt-dependent lipase 1017:1063 the human pancreatic bile-salt-dependent lipase 1017:1063 Evidence from several approaches suggests that the sugar chains of the human pancreatic bile-salt-dependent lipase possess a blood-group-related antigenic determinant. 8404898 1 47 theme oligosaccharide 142:156 arg1 chains 158:163 the N-linked oligosaccharide chains 129:163 the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor 129:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 4 48 theme innermost 744:752 arg1 residue 761:767 the innermost GlcNAc residue 740:767 the innermost GlcNAc residue 740:767 Fucose residues were identified for some trimannosyl core structures and were alpha(1-6) or alpha(1-2) linked to the innermost GlcNAc residue and a terminal Gal residue, respectively. 8404898 0 49 theme lipase 83:88 arg1 oligosaccharides 26:41 N-linked oligosaccharides 17:41 N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase 17:88 The structure of N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase. 8404898 2 50 theme P-4 445:447 arg1 filtration 449:458 Bio-Gel P-4 filtration 437:458 Bio-Gel P-4 filtration 437:458 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 2 51 theme neutral 271:277 arg1 chains 285:290 neutral sugar chains 271:290 neutral sugar chains 271:290 After hydrazinolysis, neutral sugar chains were separated from acidic chains by paper electrophoresis and were fractionated using serial column chromatography with immobilized lectins and Bio-Gel P-4 filtration. 8404898 6 52 contain have 906:909 arg2 repeats 941:947 no linear N-acetyllactosamine repeats 911:947 no linear N-acetyllactosamine repeats 911:947 Most of these structures have no linear N-acetyllactosamine repeats. 8404898 6 52 contain have 906:909 arg1 Most 881:884 Most 881:884 Most 881:884 Most of these structures have no linear N-acetyllactosamine repeats. 8404898 6 52 contain have 906:909 arg1 structures 895:904 these structures 889:904 these structures 889:904 Most of these structures have no linear N-acetyllactosamine repeats. 8404898 1 53 theme chains 158:163 arg1 structure 116:124 the structure 112:124 the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor 112:246 This study describes the structure of the N-linked oligosaccharide chains of bile-salt-dependent lipase isolated from the pancreatic juice of a normal donor. 8404898 4 54 theme core 680:683 arg1 structures 685:694 some trimannosyl core structures 663:694 some trimannosyl core structures 663:694 Fucose residues were identified for some trimannosyl core structures and were alpha(1-6) or alpha(1-2) linked to the innermost GlcNAc residue and a terminal Gal residue, respectively. 8404898 0 55 theme bile-salt-dependent 63:81 arg1 lipase 83:88 human pancreatic bile-salt-dependent lipase 46:88 human pancreatic bile-salt-dependent lipase 46:88 The structure of N-linked oligosaccharides of human pancreatic bile-salt-dependent lipase. 8404898 4 56 attach linked 730:735 arg1 residue 788:794 a terminal Gal residue 773:794 a terminal Gal residue 773:794 Fucose residues were identified for some trimannosyl core structures and were alpha(1-6) or alpha(1-2) linked to the innermost GlcNAc residue and a terminal Gal residue, respectively. 8404898 4 56 attach linked 730:735 arg2 alpha 705:709 alpha(1-6) 705:714 alpha(1-6) 705:714 Fucose residues were identified for some trimannosyl core structures and were alpha(1-6) or alpha(1-2) linked to the innermost GlcNAc residue and a terminal Gal residue, respectively. 8404898 4 56 attach linked 730:735 arg1 residue 761:767 the innermost GlcNAc residue 740:767 the innermost GlcNAc residue 740:767 Fucose residues were identified for some trimannosyl core structures and were alpha(1-6) or alpha(1-2) linked to the innermost GlcNAc residue and a terminal Gal residue, respectively. 8404898 4 57 theme trimannosyl 668:678 arg1 structures 685:694 some trimannosyl core structures 663:694 some trimannosyl core structures 663:694 Fucose residues were identified for some trimannosyl core structures and were alpha(1-6) or alpha(1-2) linked to the innermost GlcNAc residue and a terminal Gal residue, respectively. 1904026 5 0 theme Gal 787:789 arg1 1-6Gal 796:801 a terminal disaccharide Gal beta 1-6Gal 763:801 a terminal disaccharide Gal beta 1-6Gal 763:801 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 4 1 theme classical 591:599 arg1 glycan 639:644 a classical triantennary N-acetyllactosamine-type glycan 589:644 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 5 2 dep unusual 750:756 arg1 unusual 750:756 unusual 750:756 unusual 750:756 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 2 dep unusual 750:756 arg1 1-4GlcNAc 943:951 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 2 dep unusual 750:756 arg1 second 740:745 second 740:745 second 740:745 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 4 3 theme beta 720:723 arg1 1-4GlcNAc 725:733 Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 647:733 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 4 theme N-acetyllactosamine-type 614:637 arg1 glycan 639:644 a classical triantennary N-acetyllactosamine-type glycan 589:644 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 0 5 theme beta 69:72 arg1 GlcNAc 78:83 chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc 36:83 chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 36:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 4 6 theme 1-3Man 713:718 arg1 1-4GlcNAc 725:733 Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 647:733 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 7 theme triantennary 601:612 arg1 glycan 639:644 a classical triantennary N-acetyllactosamine-type glycan 589:644 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 0 8 theme GlcNAc 78:83 arg1 type 28:31 a novel type 20:31 a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 20:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 3 9 theme primary 543:549 arg1 structures 551:560 two primary structures 539:560 two primary structures 539:560 Structural analysis was by chemical analysis, chemical-ionization mass spectrometry and 400-MHz 1H-NMR spectroscopy, leading to two primary structures. 1904026 4 10 attach derived 576:582 arg1 glycan 639:644 a classical triantennary N-acetyllactosamine-type glycan 589:644 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 10 attach derived 576:582 arg2 first 567:571 first 567:571 first 567:571 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 3 11 theme Structural 411:420 arg1 analysis 422:429 Structural analysis 411:429 Structural analysis 411:429 Structural analysis was by chemical analysis, chemical-ionization mass spectrometry and 400-MHz 1H-NMR spectroscopy, leading to two primary structures. 1904026 5 12 theme beta 938:941 arg1 unusual 750:756 unusual 750:756 unusual 750:756 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 12 theme beta 938:941 arg1 1-4GlcNAc 943:951 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 12 theme beta 938:941 arg1 second 740:745 second 740:745 second 740:745 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 13 theme beta 898:901 arg1 beta 938:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 882:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 14 theme 1-6Man 931:936 arg1 beta 938:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 882:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 15 theme beta 791:794 arg1 1-6Gal 796:801 a terminal disaccharide Gal beta 1-6Gal 763:801 a terminal disaccharide Gal beta 1-6Gal 763:801 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 16 theme beta 913:916 arg1 beta 938:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 882:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 3 17 theme chemical 438:445 arg1 analysis 447:454 chemical analysis 438:454 chemical analysis 438:454 Structural analysis was by chemical analysis, chemical-ionization mass spectrometry and 400-MHz 1H-NMR spectroscopy, leading to two primary structures. 1904026 5 18 theme N-acetyllactosamine 856:874 arg1 type 876:879 the N-acetyllactosamine type 852:879 the N-acetyllactosamine type 852:879 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 0 19 theme patients 180:187 arg1 urine 171:175 the urine 167:175 the urine of patients with gangliosidosis 167:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 1 20 with patient 269:275 arg1 gangliosidosis 286:299 GM1 gangliosidosis 282:299 GM1 gangliosidosis 282:299 Two new oligosaccharides were isolated from the urine of a patient with GM1 gangliosidosis. 1904026 4 21 theme Gal 647:649 arg1 beta 694:697 Gal beta 1-4GlcNAc beta 1-2 675:701 Gal beta 1-4GlcNAc beta 1-2 675:701 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 21 theme Gal 647:649 arg1 beta 666:669 Gal beta 1-4GlcNAc beta 1-4 647:673 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 3 22 theme chemical-ionization 457:475 arg1 spectrometry 482:493 chemical-ionization mass spectrometry 457:493 chemical-ionization mass spectrometry 457:493 Structural analysis was by chemical analysis, chemical-ionization mass spectrometry and 400-MHz 1H-NMR spectroscopy, leading to two primary structures. 1904026 0 23 from type 28:31 arg1 oligosaccharide 91:105 an oligosaccharide 88:105 an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 88:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 5 24 theme terminal 765:772 arg1 1-6Gal 796:801 a terminal disaccharide Gal beta 1-6Gal 763:801 a terminal disaccharide Gal beta 1-6Gal 763:801 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 2 25 theme Final 302:306 arg1 purification 308:319 Final purification 302:319 Final purification of the oligosaccharides 302:343 Final purification of the oligosaccharides was accomplished by capillary supercritical fluid chromatography. 1904026 2 26 theme fluid 389:393 arg1 chromatography 395:408 capillary supercritical fluid chromatography 365:408 capillary supercritical fluid chromatography 365:408 Final purification of the oligosaccharides was accomplished by capillary supercritical fluid chromatography. 1904026 5 27 theme type 876:879 arg1 glycans 841:847 glycans 841:847 glycans of the N-acetyllactosamine type 841:879 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 28 theme alpha 925:929 arg1 beta 938:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 882:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 2 29 theme supercritical 375:387 arg1 chromatography 395:408 capillary supercritical fluid chromatography 365:408 capillary supercritical fluid chromatography 365:408 Final purification of the oligosaccharides was accomplished by capillary supercritical fluid chromatography. 1904026 0 30 theme novel 22:26 arg1 type 28:31 a novel type 20:31 a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 20:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 0 31 theme related 107:113 arg1 oligosaccharide 91:105 an oligosaccharide 88:105 an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 88:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 1 32 theme patient 269:275 arg1 urine 258:262 the urine 254:262 the urine of a patient with GM1 gangliosidosis 254:299 Two new oligosaccharides were isolated from the urine of a patient with GM1 gangliosidosis. 1904026 5 33 theme 1-4GlcNAc 903:911 arg1 beta 938:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 882:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 3 34 theme 400-MHz 499:505 arg1 spectroscopy 514:525 400-MHz 1H-NMR spectroscopy 499:525 400-MHz 1H-NMR spectroscopy 499:525 Structural analysis was by chemical analysis, chemical-ionization mass spectrometry and 400-MHz 1H-NMR spectroscopy, leading to two primary structures. 1904026 0 35 from GM1 163:165 arg1 urine 171:175 the urine 167:175 the urine of patients with gangliosidosis 167:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 0 36 theme N-glycosylated 118:131 arg1 glycans 141:147 N-glycosylated protein glycans 118:147 N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 118:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 4 37 theme beta 679:682 arg1 beta 694:697 Gal beta 1-4GlcNAc beta 1-2 675:701 Gal beta 1-4GlcNAc beta 1-2 675:701 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 37 theme beta 679:682 arg1 beta 666:669 Gal beta 1-4GlcNAc beta 1-4 647:673 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 0 38 with patients 180:187 arg1 gangliosidosis 194:207 gangliosidosis 194:207 gangliosidosis 194:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 3 39 theme mass 477:480 arg1 spectrometry 482:493 chemical-ionization mass spectrometry 457:493 chemical-ionization mass spectrometry 457:493 Structural analysis was by chemical analysis, chemical-ionization mass spectrometry and 400-MHz 1H-NMR spectroscopy, leading to two primary structures. 1904026 0 40 theme type 28:31 arg1 Characterization 0:15 Characterization 0:15 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 0:208 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 1 41 theme GM1 282:284 arg1 gangliosidosis 286:299 GM1 gangliosidosis 282:299 GM1 gangliosidosis 282:299 Two new oligosaccharides were isolated from the urine of a patient with GM1 gangliosidosis. 1904026 4 42 theme Gal 675:677 arg1 beta 694:697 Gal beta 1-4GlcNAc beta 1-2 675:701 Gal beta 1-4GlcNAc beta 1-2 675:701 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 42 theme Gal 675:677 arg1 beta 666:669 Gal beta 1-4GlcNAc beta 1-4 647:673 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 0 43 theme Gal 53:55 arg1 GlcNAc 78:83 chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc 36:83 chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 36:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 5 44 theme beta 886:889 arg1 beta 938:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 882:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 45 theme disaccharide 774:785 arg1 1-6Gal 796:801 a terminal disaccharide Gal beta 1-6Gal 763:801 a terminal disaccharide Gal beta 1-6Gal 763:801 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 2 46 theme oligosaccharides 328:343 arg1 purification 308:319 Final purification 302:319 Final purification of the oligosaccharides 302:343 Final purification of the oligosaccharides was accomplished by capillary supercritical fluid chromatography. 1904026 0 47 theme chain-terminator 36:51 arg1 GlcNAc 78:83 chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc 36:83 chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 36:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 0 48 theme protein 133:139 arg1 glycans 141:147 N-glycosylated protein glycans 118:147 N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 118:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 5 49 with unusual 750:756 arg1 1-6Gal 796:801 a terminal disaccharide Gal beta 1-6Gal 763:801 a terminal disaccharide Gal beta 1-6Gal 763:801 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 5 50 theme 1-2Man 918:923 arg1 beta 938:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 882:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 3 51 theme 1H-NMR 507:512 arg1 spectroscopy 514:525 400-MHz 1H-NMR spectroscopy 499:525 400-MHz 1H-NMR spectroscopy 499:525 Structural analysis was by chemical analysis, chemical-ionization mass spectrometry and 400-MHz 1H-NMR spectroscopy, leading to two primary structures. 1904026 5 52 theme Gal 882:884 arg1 beta 938:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 882:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 4 53 theme beta 651:654 arg1 beta 694:697 Gal beta 1-4GlcNAc beta 1-2 675:701 Gal beta 1-4GlcNAc beta 1-2 675:701 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 53 theme beta 651:654 arg1 beta 666:669 Gal beta 1-4GlcNAc beta 1-4 647:673 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 54 dep glycan 639:644 arg1 1-4GlcNAc 725:733 Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 647:733 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 0 55 from GlcNAc 78:83 arg1 oligosaccharide 91:105 an oligosaccharide 88:105 an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 88:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 1 56 attach isolated 240:247 arg1 urine 258:262 the urine 254:262 the urine of a patient with GM1 gangliosidosis 254:299 Two new oligosaccharides were isolated from the urine of a patient with GM1 gangliosidosis. 1904026 1 56 attach isolated 240:247 arg2 oligosaccharides 218:233 Two new oligosaccharides 210:233 Two new oligosaccharides 210:233 Two new oligosaccharides were isolated from the urine of a patient with GM1 gangliosidosis. 1904026 0 57 gly N-glycosylated 118:131 arg1 glycans 141:147 N-glycosylated protein glycans 118:147 N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 118:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 1 58 theme new 214:216 arg1 oligosaccharides 218:233 Two new oligosaccharides 210:233 Two new oligosaccharides 210:233 Two new oligosaccharides were isolated from the urine of a patient with GM1 gangliosidosis. 1904026 0 59 theme 1-6Gal 62:67 arg1 GlcNAc 78:83 chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc 36:83 chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 36:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 2 60 theme capillary 365:373 arg1 chromatography 395:408 capillary supercritical fluid chromatography 365:408 capillary supercritical fluid chromatography 365:408 Final purification of the oligosaccharides was accomplished by capillary supercritical fluid chromatography. 1904026 4 61 theme 1-4GlcNAc 684:692 arg1 beta 694:697 Gal beta 1-4GlcNAc beta 1-2 675:701 Gal beta 1-4GlcNAc beta 1-2 675:701 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 61 theme 1-4GlcNAc 684:692 arg1 beta 666:669 Gal beta 1-4GlcNAc beta 1-4 647:673 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 62 theme beta 666:669 arg1 1-4GlcNAc 725:733 Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 647:733 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 0 63 theme beta 57:60 arg1 GlcNAc 78:83 chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc 36:83 chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 36:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 1904026 4 64 theme 1-4GlcNAc 656:664 arg1 beta 694:697 Gal beta 1-4GlcNAc beta 1-2 675:701 Gal beta 1-4GlcNAc beta 1-2 675:701 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 4 64 theme 1-4GlcNAc 656:664 arg1 beta 666:669 Gal beta 1-4GlcNAc beta 1-4 647:673 a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc 589:733 The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. 1904026 5 65 theme 1-6Gal 891:896 arg1 beta 938:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 882:941 Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc 882:951 The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. 1904026 0 66 from oligosaccharide 91:105 arg1 type 28:31 a novel type 20:31 a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis 20:207 Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1-4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. 3179269 3 0 theme ODS 753:755 arg1 column 764:769 an ODS silica column 750:769 an ODS silica column 750:769 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 3 1 theme oligosaccharide 520:534 arg1 chains 536:541 the oligosaccharide chains 516:541 the oligosaccharide chains thus obtained 516:555 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 5 2 theme HPLC 1066:1069 arg1 digestion 1036:1044 sequential exoglycosidase digestion 1010:1044 sequential exoglycosidase digestion 1010:1044 The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. 3179269 5 2 theme HPLC 1066:1069 arg1 kind 1058:1061 another kind 1050:1061 another kind of HPLC 1050:1069 The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. 3179269 0 3 theme erythropoietins 85:99 arg1 oligosaccharides 41:56 N-linked oligosaccharides 32:56 N-linked oligosaccharides of urinary and recombinant erythropoietins 32:99 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins. 3179269 6 4 theme proton 1129:1134 arg1 resonance 1153:1161 proton nuclear magnetic resonance 1129:1161 high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy 1113:1183 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 6 4 theme proton 1129:1134 arg1 NMR 1167:1169 1H NMR 1164:1169 1H NMR 1164:1169 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 3 5 theme chains 536:541 arg1 ends 508:511 The reducing ends 495:511 The reducing ends of the oligosaccharide chains thus obtained 495:555 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 3 5 theme chains 536:541 arg1 aminated 562:569 aminated 562:569 aminated 562:569 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 5 6 with kind 1058:1061 arg1 column 1092:1097 an amide-silica column 1076:1097 an amide-silica column 1076:1097 The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. 3179269 3 7 theme silica 757:762 arg1 column 764:769 an ODS silica column 750:769 an ODS silica column 750:769 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 6 8 theme high-resolution 1113:1127 arg1 spectroscopy 1172:1183 high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy 1113:1183 high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy 1113:1183 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 1 9 theme recombinant 278:288 arg1 r-EPO 306:310 r-EPO 306:310 r-EPO 306:310 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 1 9 theme recombinant 278:288 arg1 erythropoietin 290:303 recombinant erythropoietin 278:303 recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells 278:357 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 5 10 with digestion 1036:1044 arg1 column 1092:1097 an amide-silica column 1076:1097 an amide-silica column 1076:1097 The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. 3179269 6 11 theme 1H 1164:1165 arg1 resonance 1153:1161 proton nuclear magnetic resonance 1129:1161 high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy 1113:1183 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 6 11 theme 1H 1164:1165 arg1 NMR 1167:1169 1H NMR 1164:1169 1H NMR 1164:1169 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 5 12 theme oligosaccharide 947:961 arg1 structure 929:937 The structure 925:937 The structure of each oligosaccharide thus isolated 925:975 The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. 3179269 6 13 theme methylation 1189:1199 arg1 analyses 1201:1208 methylation analyses 1189:1208 methylation analyses 1189:1208 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 0 14 theme structural 12:21 arg1 study 23:27 Comparative structural study 0:27 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins 0:99 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins. 3179269 2 15 link Asparagine-linked 360:376 arg1 oligosaccharides 386:401 Asparagine-linked neutral oligosaccharides 360:401 Asparagine-linked neutral oligosaccharides 360:401 Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. 3179269 0 16 theme Comparative 0:10 arg1 study 23:27 Comparative structural study 0:27 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins 0:99 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins. 3179269 3 17 theme liquid 718:723 arg1 HPLC 741:744 HPLC 741:744 HPLC 741:744 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 3 17 theme liquid 718:723 arg1 chromatography 725:738 high-performance liquid chromatography 701:738 high-performance liquid chromatography (HPLC) on an ODS silica column 701:769 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 2 18 theme glycopeptidase 460:473 arg1 digestion 484:492 N-oligosaccharide glycopeptidase (almond) digestion 442:492 N-oligosaccharide glycopeptidase (almond) digestion 442:492 Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. 3179269 0 19 link N-linked 32:39 arg1 oligosaccharides 41:56 N-linked oligosaccharides 32:56 N-linked oligosaccharides of urinary and recombinant erythropoietins 32:99 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins. 3179269 3 20 theme fluorescent 578:588 arg1 reagent 590:596 a fluorescent reagent 576:596 a fluorescent reagent 576:596 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 3 20 theme fluorescent 578:588 arg1 2-aminopyridine 599:613 2-aminopyridine 599:613 2-aminopyridine 599:613 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 2 21 theme N-oligosaccharide 442:458 arg1 almond 476:481 almond 476:481 almond 476:481 Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. 3179269 2 21 theme N-oligosaccharide 442:458 arg1 glycopeptidase 460:473 N-oligosaccharide glycopeptidase 442:473 N-oligosaccharide glycopeptidase (almond) digestion 442:492 Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. 3179269 2 22 theme neutral 378:384 arg1 oligosaccharides 386:401 Asparagine-linked neutral oligosaccharides 360:401 Asparagine-linked neutral oligosaccharides 360:401 Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. 3179269 5 23 theme amide-silica 1079:1090 arg1 column 1092:1097 an amide-silica column 1076:1097 an amide-silica column 1076:1097 The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. 3179269 1 24 theme aplastic 211:218 arg1 patients 227:234 aplastic anemic patients 211:234 aplastic anemic patients 211:234 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 0 25 theme oligosaccharides 41:56 arg1 study 23:27 Comparative structural study 0:27 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins 0:99 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins. 3179269 5 26 theme exoglycosidase 1021:1034 arg1 digestion 1036:1044 sequential exoglycosidase digestion 1010:1044 sequential exoglycosidase digestion 1010:1044 The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. 3179269 3 27 from chromatography 725:738 arg1 column 764:769 an ODS silica column 750:769 an ODS silica column 750:769 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 2 28 theme EPO 427:429 arg1 protein 431:437 each EPO protein 422:437 each EPO protein 422:437 Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. 3179269 5 29 theme digestion 1036:1044 arg1 combination 995:1005 a combination 993:1005 a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column 993:1097 The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. 3179269 1 30 theme anemic 220:225 arg1 patients 227:234 aplastic anemic patients 211:234 aplastic anemic patients 211:234 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 0 31 theme N-linked 32:39 arg1 oligosaccharides 41:56 N-linked oligosaccharides 32:56 N-linked oligosaccharides of urinary and recombinant erythropoietins 32:99 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins. 3179269 3 32 with aminated 562:569 arg1 reagent 590:596 a fluorescent reagent 576:596 a fluorescent reagent 576:596 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 3 32 with aminated 562:569 arg1 2-aminopyridine 599:613 2-aminopyridine 599:613 2-aminopyridine 599:613 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 1 33 theme patients 227:234 arg1 urine 202:206 urine 202:206 urine of aplastic anemic patients 202:234 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 0 34 theme urinary 61:67 arg1 erythropoietins 85:99 urinary and recombinant erythropoietins 61:99 urinary and recombinant erythropoietins 61:99 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins. 3179269 4 35 theme one-step 900:907 arg1 procedure 914:922 the one-step HPLC procedure 896:922 the one-step HPLC procedure 896:922 More than 8 and 13 kinds of oligosaccharide fractions for u-EPO and r-EPO (BHK), respectively, were completely separated by the one-step HPLC procedure. 3179269 3 36 theme oligosaccharides 667:682 arg1 derivatives 648:658 pyridylamino derivatives 635:658 pyridylamino derivatives of the oligosaccharides 635:682 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 6 37 theme r-EPO 1242:1246 arg1 case 1234:1237 the case 1230:1237 the case of r-EPO (BHK) 1230:1252 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 6 38 theme nuclear 1136:1142 arg1 resonance 1153:1161 proton nuclear magnetic resonance 1129:1161 high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy 1113:1183 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 6 38 theme nuclear 1136:1142 arg1 NMR 1167:1169 1H NMR 1164:1169 1H NMR 1164:1169 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 1 39 theme N-linked 124:131 arg1 oligosaccharides 133:148 the N-linked oligosaccharides 120:148 the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients 120:234 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 1 40 theme baby 327:330 arg1 BHK 348:350 BHK 348:350 BHK 348:350 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 1 40 theme baby 327:330 arg1 kidney 340:345 baby hamster kidney 327:345 baby hamster kidney (BHK) cells 327:357 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 2 41 attach released 408:415 arg2 oligosaccharides 386:401 Asparagine-linked neutral oligosaccharides 360:401 Asparagine-linked neutral oligosaccharides 360:401 Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. 3179269 2 41 attach released 408:415 arg1 protein 431:437 each EPO protein 422:437 each EPO protein 422:437 Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. 3179269 5 42 theme kind 1058:1061 arg1 combination 995:1005 a combination 993:1005 a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column 993:1097 The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. 3179269 1 43 theme oligosaccharides 133:148 arg1 structures 106:115 The structures 102:115 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients 102:234 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 1 44 theme hamster 332:338 arg1 BHK 348:350 BHK 348:350 BHK 348:350 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 1 44 theme hamster 332:338 arg1 kidney 340:345 baby hamster kidney 327:345 baby hamster kidney (BHK) cells 327:357 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 1 45 link N-linked 124:131 arg1 oligosaccharides 133:148 the N-linked oligosaccharides 120:148 the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients 120:234 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 4 46 theme fractions 816:824 arg1 kinds 791:795 More than 8 and 13 kinds 772:795 More than 8 and 13 kinds of oligosaccharide fractions for u-EPO and r-EPO (BHK) 772:850 More than 8 and 13 kinds of oligosaccharide fractions for u-EPO and r-EPO (BHK), respectively, were completely separated by the one-step HPLC procedure. 3179269 3 47 theme derivatives 648:658 arg1 mixture 624:630 the mixture 620:630 the mixture of pyridylamino derivatives of the oligosaccharides 620:682 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 3 48 theme reducing 499:506 arg1 ends 508:511 The reducing ends 495:511 The reducing ends of the oligosaccharide chains thus obtained 495:555 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 3 48 theme reducing 499:506 arg1 aminated 562:569 aminated 562:569 aminated 562:569 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 6 49 theme magnetic 1144:1151 arg1 resonance 1153:1161 proton nuclear magnetic resonance 1129:1161 high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy 1113:1183 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 6 49 theme magnetic 1144:1151 arg1 NMR 1167:1169 1H NMR 1164:1169 1H NMR 1164:1169 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 4 50 theme HPLC 909:912 arg1 procedure 914:922 the one-step HPLC procedure 896:922 the one-step HPLC procedure 896:922 More than 8 and 13 kinds of oligosaccharide fractions for u-EPO and r-EPO (BHK), respectively, were completely separated by the one-step HPLC procedure. 3179269 4 51 theme oligosaccharide 800:814 arg1 fractions 816:824 oligosaccharide fractions 800:824 oligosaccharide fractions 800:824 More than 8 and 13 kinds of oligosaccharide fractions for u-EPO and r-EPO (BHK), respectively, were completely separated by the one-step HPLC procedure. 3179269 2 52 theme Asparagine-linked 360:376 arg1 oligosaccharides 386:401 Asparagine-linked neutral oligosaccharides 360:401 Asparagine-linked neutral oligosaccharides 360:401 Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. 3179269 6 53 theme resonance 1153:1161 arg1 spectroscopy 1172:1183 high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy 1113:1183 high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy 1113:1183 Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK). 3179269 0 54 theme recombinant 73:83 arg1 erythropoietins 85:99 urinary and recombinant erythropoietins 61:99 urinary and recombinant erythropoietins 61:99 Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins. 3179269 3 55 theme high-performance 701:716 arg1 HPLC 741:744 HPLC 741:744 HPLC 741:744 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 3 55 theme high-performance 701:716 arg1 chromatography 725:738 high-performance liquid chromatography 701:738 high-performance liquid chromatography (HPLC) on an ODS silica column 701:769 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 5 56 theme sequential 1010:1019 arg1 digestion 1036:1044 sequential exoglycosidase digestion 1010:1044 sequential exoglycosidase digestion 1010:1044 The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. 3179269 1 57 theme urinary 157:163 arg1 erythropoietin 165:178 the urinary erythropoietin 153:178 the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients 153:234 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 1 57 theme urinary 157:163 arg1 u-EPO 181:185 u-EPO 181:185 u-EPO 181:185 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 1 58 theme kidney 340:345 arg1 cells 353:357 baby hamster kidney (BHK) cells 327:357 baby hamster kidney (BHK) cells 327:357 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3179269 3 59 theme pyridylamino 635:646 arg1 derivatives 648:658 pyridylamino derivatives 635:658 pyridylamino derivatives of the oligosaccharides 635:682 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. 3179269 1 60 theme erythropoietin 165:178 arg1 oligosaccharides 133:148 the N-linked oligosaccharides 120:148 the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients 120:234 The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. 3346214 4 0 theme 2----6Gal 930:938 arg1 linkage 940:946 the NeuAc alpha 2----6Gal linkage 914:946 the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage 914:994 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 1 1 theme affinity 415:422 arg1 chromatography 424:437 lectin affinity chromatography 408:437 lectin affinity chromatography 408:437 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 6 2 theme glycoprotein 1340:1351 arg1 hormone 1353:1359 glycoprotein hormone 1340:1359 glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one 1340:1444 This paper proved, for the first time, that recombinant technique can produce glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one. 3346214 2 3 contain had 500:502 arg2 chains 534:539 three asparagine-linked sugar chains 504:539 three asparagine-linked sugar chains 504:539 Both erythropoietins had three asparagine-linked sugar chains in one molecule, all of which were acidic complex type. 3346214 2 3 contain had 500:502 arg1 erythropoietins 484:498 Both erythropoietins 479:498 Both erythropoietins 479:498 Both erythropoietins had three asparagine-linked sugar chains in one molecule, all of which were acidic complex type. 3346214 3 4 theme Structural 597:606 arg1 analysis 608:615 Structural analysis 597:615 Structural analysis of them 597:623 Structural analysis of them revealed that the sugar chains from both erythropoietins are quite similar except for sialyl linkage. 3346214 1 5 theme asparagine-linked 172:188 arg1 chains 196:201 The asparagine-linked sugar chains 168:201 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin 168:330 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 4 6 theme NeuAc 918:922 arg1 linkage 940:946 the NeuAc alpha 2----6Gal linkage 914:946 the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage 914:994 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 6 7 theme recombinant 1306:1316 arg1 technique 1318:1326 recombinant technique 1306:1326 recombinant technique 1306:1326 This paper proved, for the first time, that recombinant technique can produce glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one. 3346214 5 8 from units 1115:1119 arg1 moieties 1142:1149 their outer chain moieties 1124:1149 their outer chain moieties in common 1124:1159 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 0 9 link asparagine-linked 25:41 arg1 chains 49:54 the asparagine-linked sugar chains 21:54 the asparagine-linked sugar chains of human erythropoietins 21:79 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 6 10 theme sugar 1415:1419 arg1 chains 1421:1426 the major sugar chains 1405:1426 the major sugar chains of the native one 1405:1444 This paper proved, for the first time, that recombinant technique can produce glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one. 3346214 1 11 theme human 206:210 arg1 erythropoietin 212:225 human erythropoietin 206:225 human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin 206:330 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 0 12 theme recombinant 127:137 arg1 cells 161:165 recombinant Chinese hamster ovary cells 127:165 recombinant Chinese hamster ovary cells 127:165 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 0 13 theme hamster 147:153 arg1 cells 161:165 recombinant Chinese hamster ovary cells 127:165 recombinant Chinese hamster ovary cells 127:165 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 1 14 theme P-4 452:454 arg1 chromatography 463:476 Bio-Gel P-4 column chromatography 444:476 Bio-Gel P-4 column chromatography 444:476 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 1 15 theme column 456:461 arg1 chromatography 463:476 Bio-Gel P-4 column chromatography 444:476 Bio-Gel P-4 column chromatography 444:476 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 4 16 theme alpha 972:976 arg1 linkage 988:994 the NeuAc alpha 2----3Gal linkage 962:994 the NeuAc alpha 2----3Gal linkage 962:994 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 4 17 theme Chinese 786:792 arg1 cells 808:812 recombinant Chinese hamster ovary cells 774:812 recombinant Chinese hamster ovary cells 774:812 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 0 18 theme cells 161:165 arg1 medium 117:122 the culture medium 105:122 the culture medium of recombinant Chinese hamster ovary cells 105:165 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 0 18 theme cells 161:165 arg1 urine 95:99 urine 95:99 urine 95:99 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 5 19 theme chain 1136:1140 arg1 moieties 1142:1149 their outer chain moieties 1124:1149 their outer chain moieties in common 1124:1159 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 20 gly fucosylated 1028:1038 arg1 type 1063:1066 fucosylated tetraantennary complex type 1028:1066 fucosylated tetraantennary complex type 1028:1066 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 21 from moieties 1142:1149 arg1 common 1154:1159 common 1154:1159 common 1154:1159 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 4 22 theme erythropoietin 747:760 arg1 chains 737:742 All sugar chains 727:742 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells 727:812 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 5 23 theme triantennary 1205:1216 arg1 chains 1240:1245 2,4- and 2,6-branched triantennary and biantennary sugar chains 1183:1245 chains 1240:1245 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 23 theme triantennary 1205:1216 arg1 triantennary 1205:1216 2,4- and 2,6-branched triantennary and biantennary sugar chains 1183:1245 triantennary 1205:1216 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 23 theme triantennary 1205:1216 arg1 amounts 1172:1178 small amounts 1166:1178 small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains 1166:1245 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 2 24 theme acidic 576:581 arg1 type 591:594 acidic complex type 576:594 acidic complex type 576:594 Both erythropoietins had three asparagine-linked sugar chains in one molecule, all of which were acidic complex type. 3346214 6 25 theme native 1435:1440 arg1 one 1442:1444 the native one 1431:1444 the native one 1431:1444 This paper proved, for the first time, that recombinant technique can produce glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one. 3346214 5 26 theme small 1166:1170 arg1 chains 1240:1245 2,4- and 2,6-branched triantennary and biantennary sugar chains 1183:1245 chains 1240:1245 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 26 theme small 1166:1170 arg1 triantennary 1205:1216 2,4- and 2,6-branched triantennary and biantennary sugar chains 1183:1245 triantennary 1205:1216 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 26 theme small 1166:1170 arg1 amounts 1172:1178 small amounts 1166:1178 small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains 1166:1245 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 27 theme fucosylated 1028:1038 arg1 type 1063:1066 fucosylated tetraantennary complex type 1028:1066 fucosylated tetraantennary complex type 1028:1066 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 4 28 theme alpha 837:841 arg1 linkage 853:859 only the NeuAc alpha 2----3Gal linkage 822:859 only the NeuAc alpha 2----3Gal linkage 822:859 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 1 29 theme lectin 408:413 arg1 chromatography 424:437 lectin affinity chromatography 408:437 lectin affinity chromatography 408:437 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 5 30 theme complex 1055:1061 arg1 type 1063:1066 fucosylated tetraantennary complex type 1028:1066 fucosylated tetraantennary complex type 1028:1066 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 2 31 from chains 534:539 arg1 molecule 548:555 one molecule 544:555 one molecule 544:555 Both erythropoietins had three asparagine-linked sugar chains in one molecule, all of which were acidic complex type. 3346214 2 32 link asparagine-linked 510:526 arg1 chains 534:539 three asparagine-linked sugar chains 504:539 three asparagine-linked sugar chains 504:539 Both erythropoietins had three asparagine-linked sugar chains in one molecule, all of which were acidic complex type. 3346214 4 33 theme ovary 802:806 arg1 cells 808:812 recombinant Chinese hamster ovary cells 774:812 recombinant Chinese hamster ovary cells 774:812 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 0 34 theme Comparative 0:10 arg1 study 12:16 Comparative study 0:16 Comparative study of the asparagine-linked sugar chains of human erythropoietins 0:79 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 1 35 theme occurring 293:301 arg1 erythropoietin 317:330 naturally occurring human urinary erythropoietin 283:330 naturally occurring human urinary erythropoietin 283:330 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 5 36 theme sugar 1007:1011 arg1 chains 1013:1018 The major sugar chains 997:1018 The major sugar chains 997:1018 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 1 37 theme urinary 309:315 arg1 erythropoietin 317:330 naturally occurring human urinary erythropoietin 283:330 naturally occurring human urinary erythropoietin 283:330 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 0 38 theme asparagine-linked 25:41 arg1 chains 49:54 the asparagine-linked sugar chains 21:54 the asparagine-linked sugar chains of human erythropoietins 21:79 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 5 39 theme biantennary 1222:1232 arg1 chains 1240:1245 2,4- and 2,6-branched triantennary and biantennary sugar chains 1183:1245 chains 1240:1245 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 40 theme repeating 1105:1113 arg1 units 1115:1119 N-acetyllactosamine repeating units 1085:1119 N-acetyllactosamine repeating units in their outer chain moieties in common 1085:1159 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 2 41 theme sugar 528:532 arg1 chains 534:539 three asparagine-linked sugar chains 504:539 three asparagine-linked sugar chains 504:539 Both erythropoietins had three asparagine-linked sugar chains in one molecule, all of which were acidic complex type. 3346214 0 42 theme human 59:63 arg1 erythropoietins 65:79 human erythropoietins 59:79 human erythropoietins 59:79 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 4 43 theme urinary 883:889 arg1 erythropoietin 891:904 human urinary erythropoietin 877:904 human urinary erythropoietin 877:904 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 0 44 theme chains 49:54 arg1 study 12:16 Comparative study 0:16 Comparative study of the asparagine-linked sugar chains of human erythropoietins 0:79 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 5 45 theme chains 1240:1245 arg1 chains 1240:1245 2,4- and 2,6-branched triantennary and biantennary sugar chains 1183:1245 chains 1240:1245 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 45 theme chains 1240:1245 arg1 triantennary 1205:1216 2,4- and 2,6-branched triantennary and biantennary sugar chains 1183:1245 triantennary 1205:1216 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 45 theme chains 1240:1245 arg1 amounts 1172:1178 small amounts 1166:1178 small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains 1166:1245 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 1 46 theme Chinese 251:257 arg1 cells 273:277 recombinant Chinese hamster ovary cells 239:277 recombinant Chinese hamster ovary cells 239:277 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 6 47 theme carbohydrate 1367:1378 arg1 structures 1380:1389 structures 1380:1389 structures 1380:1389 This paper proved, for the first time, that recombinant technique can produce glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one. 3346214 1 48 theme ovary 267:271 arg1 cells 273:277 recombinant Chinese hamster ovary cells 239:277 recombinant Chinese hamster ovary cells 239:277 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 4 49 theme alpha 924:928 arg1 linkage 940:946 the NeuAc alpha 2----6Gal linkage 914:946 the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage 914:994 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 3 50 theme them 620:623 arg1 analysis 608:615 Structural analysis 597:615 Structural analysis of them 597:623 Structural analysis of them revealed that the sugar chains from both erythropoietins are quite similar except for sialyl linkage. 3346214 1 51 theme sugar 190:194 arg1 chains 196:201 The asparagine-linked sugar chains 168:201 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin 168:330 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 4 52 contain contain 814:820 arg1 chains 737:742 All sugar chains 727:742 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells 727:812 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 4 52 contain contain 814:820 arg2 linkage 853:859 only the NeuAc alpha 2----3Gal linkage 822:859 only the NeuAc alpha 2----3Gal linkage 822:859 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 4 53 theme 2----3Gal 978:986 arg1 linkage 988:994 the NeuAc alpha 2----3Gal linkage 962:994 the NeuAc alpha 2----3Gal linkage 962:994 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 0 54 theme Chinese 139:145 arg1 cells 161:165 recombinant Chinese hamster ovary cells 127:165 recombinant Chinese hamster ovary cells 127:165 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 3 55 theme sugar 643:647 arg1 chains 649:654 the sugar chains 639:654 the sugar chains from both erythropoietins 639:680 Structural analysis of them revealed that the sugar chains from both erythropoietins are quite similar except for sialyl linkage. 3346214 3 55 theme sugar 643:647 arg1 similar 692:698 similar 692:698 similar 692:698 Structural analysis of them revealed that the sugar chains from both erythropoietins are quite similar except for sialyl linkage. 3346214 1 56 theme erythropoietin 212:225 arg1 chains 196:201 The asparagine-linked sugar chains 168:201 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin 168:330 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 2 57 theme complex 583:589 arg1 type 591:594 acidic complex type 576:594 acidic complex type 576:594 Both erythropoietins had three asparagine-linked sugar chains in one molecule, all of which were acidic complex type. 3346214 0 58 theme ovary 155:159 arg1 cells 161:165 recombinant Chinese hamster ovary cells 127:165 recombinant Chinese hamster ovary cells 127:165 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 1 59 theme Bio-Gel 444:450 arg1 chromatography 463:476 Bio-Gel P-4 column chromatography 444:476 Bio-Gel P-4 column chromatography 444:476 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 6 60 theme first 1289:1293 arg1 time 1295:1298 the first time 1285:1298 the first time 1285:1298 This paper proved, for the first time, that recombinant technique can produce glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one. 3346214 5 61 theme outer 1130:1134 arg1 moieties 1142:1149 their outer chain moieties 1124:1149 their outer chain moieties in common 1124:1159 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 4 62 theme NeuAc 966:970 arg1 linkage 988:994 the NeuAc alpha 2----3Gal linkage 962:994 the NeuAc alpha 2----3Gal linkage 962:994 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 4 63 theme recombinant 774:784 arg1 cells 808:812 recombinant Chinese hamster ovary cells 774:812 recombinant Chinese hamster ovary cells 774:812 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 0 64 theme erythropoietins 65:79 arg1 chains 49:54 the asparagine-linked sugar chains 21:54 the asparagine-linked sugar chains of human erythropoietins 21:79 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 4 65 contain contain 906:912 arg2 linkage 940:946 the NeuAc alpha 2----6Gal linkage 914:946 the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage 914:994 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 4 65 contain contain 906:912 arg1 those 868:872 those 868:872 those 868:872 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 4 66 theme sugar 731:735 arg1 chains 737:742 All sugar chains 727:742 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells 727:812 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 5 67 theme 2,6-branched 1192:1203 arg1 triantennary 1205:1216 2,4- and 2,6-branched triantennary and biantennary sugar chains 1183:1245 triantennary 1205:1216 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 6 68 gly glycoprotein 1340:1351 arg1 glycoprotein 1340:1351 glycoprotein hormone 1340:1359 glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one 1340:1444 This paper proved, for the first time, that recombinant technique can produce glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one. 3346214 6 69 theme one 1442:1444 arg1 chains 1421:1426 the major sugar chains 1405:1426 the major sugar chains of the native one 1405:1444 This paper proved, for the first time, that recombinant technique can produce glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one. 3346214 1 70 theme paper 385:389 arg1 electrophoresis 391:405 paper electrophoresis 385:405 paper electrophoresis 385:405 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 0 71 theme culture 109:115 arg1 medium 117:122 the culture medium 105:122 the culture medium of recombinant Chinese hamster ovary cells 105:165 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 5 72 theme tetraantennary 1040:1053 arg1 type 1063:1066 fucosylated tetraantennary complex type 1028:1066 fucosylated tetraantennary complex type 1028:1066 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 4 73 theme NeuAc 831:835 arg1 linkage 853:859 only the NeuAc alpha 2----3Gal linkage 822:859 only the NeuAc alpha 2----3Gal linkage 822:859 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 3 74 from erythropoietins 666:680 arg1 chains 649:654 the sugar chains 639:654 the sugar chains from both erythropoietins 639:680 Structural analysis of them revealed that the sugar chains from both erythropoietins are quite similar except for sialyl linkage. 3346214 3 74 from erythropoietins 666:680 arg1 similar 692:698 similar 692:698 similar 692:698 Structural analysis of them revealed that the sugar chains from both erythropoietins are quite similar except for sialyl linkage. 3346214 5 75 theme 2,4- 1183:1186 arg1 triantennary 1205:1216 2,4- and 2,6-branched triantennary and biantennary sugar chains 1183:1245 triantennary 1205:1216 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 76 theme major 1001:1005 arg1 chains 1013:1018 The major sugar chains 997:1018 The major sugar chains 997:1018 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 6 77 theme major 1409:1413 arg1 chains 1421:1426 the major sugar chains 1405:1426 the major sugar chains of the native one 1405:1444 This paper proved, for the first time, that recombinant technique can produce glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one. 3346214 1 78 link asparagine-linked 172:188 arg1 chains 196:201 The asparagine-linked sugar chains 168:201 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin 168:330 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 4 79 theme hamster 794:800 arg1 cells 808:812 recombinant Chinese hamster ovary cells 774:812 recombinant Chinese hamster ovary cells 774:812 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 1 80 theme human 303:307 arg1 erythropoietin 317:330 naturally occurring human urinary erythropoietin 283:330 naturally occurring human urinary erythropoietin 283:330 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 0 81 theme sugar 43:47 arg1 chains 49:54 the asparagine-linked sugar chains 21:54 the asparagine-linked sugar chains of human erythropoietins 21:79 Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. 3346214 5 82 theme N-acetyllactosamine 1085:1103 arg1 units 1115:1119 N-acetyllactosamine repeating units 1085:1119 N-acetyllactosamine repeating units in their outer chain moieties in common 1085:1159 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 5 83 theme sugar 1234:1238 arg1 chains 1240:1245 2,4- and 2,6-branched triantennary and biantennary sugar chains 1183:1245 chains 1240:1245 The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4- and 2,6-branched triantennary and biantennary sugar chains were detected. 3346214 2 84 theme asparagine-linked 510:526 arg1 chains 534:539 three asparagine-linked sugar chains 504:539 three asparagine-linked sugar chains 504:539 Both erythropoietins had three asparagine-linked sugar chains in one molecule, all of which were acidic complex type. 3346214 4 85 theme human 877:881 arg1 erythropoietin 891:904 human urinary erythropoietin 877:904 human urinary erythropoietin 877:904 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 3 86 theme sialyl 711:716 arg1 linkage 718:724 sialyl linkage 711:724 sialyl linkage 711:724 Structural analysis of them revealed that the sugar chains from both erythropoietins are quite similar except for sialyl linkage. 3346214 4 87 theme 2----3Gal 843:851 arg1 linkage 853:859 only the NeuAc alpha 2----3Gal linkage 822:859 only the NeuAc alpha 2----3Gal linkage 822:859 All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. 3346214 1 88 theme recombinant 239:249 arg1 cells 273:277 recombinant Chinese hamster ovary cells 239:277 recombinant Chinese hamster ovary cells 239:277 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 3346214 1 89 theme hamster 259:265 arg1 cells 273:277 recombinant Chinese hamster ovary cells 239:277 recombinant Chinese hamster ovary cells 239:277 The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. 8981093 0 0 theme Q 106:106 arg1 chromatography 115:128 Mono Q column chromatography 101:128 Mono Q column chromatography 101:128 Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase. 8981093 1 1 theme recombinant 341:351 arg1 EPO 359:361 cell-derived recombinant human EPO 328:361 baby hamster kidney cell-derived recombinant human EPO 308:361 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 2 2 theme asialo 597:602 arg1 oligosaccharides 613:628 asialo N-linked oligosaccharides 597:628 asialo N-linked oligosaccharides of each fraction 597:645 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 3 3 theme sialic 719:724 arg1 content 731:737 the sialic acid content 715:737 the sialic acid content of the fractionated samples 715:765 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 2 4 link N-linked 604:611 arg1 oligosaccharides 613:628 asialo N-linked oligosaccharides 597:628 asialo N-linked oligosaccharides of each fraction 597:645 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 5 5 theme alpha 1134:1138 arg1 2,6-sialyltransferase 1140:1160 alpha 2,6-sialyltransferase 1134:1160 alpha 2,6-sialyltransferase 1134:1160 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 0 6 theme Mono 101:104 arg1 chromatography 115:128 Mono Q column chromatography 101:128 Mono Q column chromatography 101:128 Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase. 8981093 1 7 theme human 353:357 arg1 EPO 359:361 cell-derived recombinant human EPO 328:361 baby hamster kidney cell-derived recombinant human EPO 308:361 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 3 8 theme linear 659:664 arg1 relationship 666:677 a linear relationship 657:677 a linear relationship between the in vivo bioactivity 657:709 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 5 9 theme other 1198:1202 arg1 fractions 1204:1212 the other fractions 1194:1212 the other fractions with high sialic acid contents 1194:1243 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 1 10 theme mol 271:273 arg1 mol-1 275:279 9.5 to 13.8 mol mol-1 259:279 9.5 to 13.8 mol mol-1 of EPO 259:286 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 5 11 theme in 1031:1032 arg1 bioactivity 1039:1049 the in vivo bioactivity 1027:1049 the in vivo bioactivity of some fractions with low sialic acid contents 1027:1097 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 5 12 theme low 1074:1076 arg1 contents 1090:1097 low sialic acid contents 1074:1097 low sialic acid contents 1074:1097 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 5 13 theme fractions 1204:1212 arg1 bioactivity 1179:1189 the in vivo bioactivity 1167:1189 the in vivo bioactivity of the other fractions with high sialic acid contents 1167:1243 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 4 14 theme inverse 907:913 arg1 relationship 915:926 an inverse relationship 904:926 an inverse relationship between the in vitro bioactivity 904:959 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 0 15 theme column 108:113 arg1 chromatography 115:128 Mono Q column chromatography 101:128 Mono Q column chromatography 101:128 Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase. 8981093 3 16 theme acid 726:729 arg1 content 731:737 the sialic acid content 715:737 the sialic acid content of the fractionated samples 715:765 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 3 17 dep in 691:692 arg1 vivo 694:697 vivo 694:697 vivo 694:697 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 3 18 theme EPO 880:882 arg1 mol-1 871:875 12.4 mol mol-1 862:875 12.4 mol mol-1 of EPO 862:882 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 2 19 from change 567:572 arg1 constitution 581:592 the constitution 577:592 the constitution of asialo N-linked oligosaccharides of each fraction 577:645 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 1 20 theme Mono 366:369 arg1 chromatography 380:393 Mono Q column chromatography 366:393 Mono Q column chromatography 366:393 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 4 21 located observed 996:1003 arg2 relationship 915:926 an inverse relationship 904:926 an inverse relationship between the in vitro bioactivity 904:959 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 4 21 located observed 996:1003 arg2 content 977:983 sialic acid content 965:983 sialic acid content of EPO 965:990 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 4 21 located observed 996:1003 arg1 hand 898:901 the other hand 888:901 the other hand 888:901 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 2 22 theme fraction 638:645 arg1 oligosaccharides 613:628 asialo N-linked oligosaccharides 597:628 asialo N-linked oligosaccharides of each fraction 597:645 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 5 23 with fractions 1204:1212 arg1 contents 1236:1243 high sialic acid contents 1219:1243 high sialic acid contents 1219:1243 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 5 24 theme sialic 1224:1229 arg1 contents 1236:1243 high sialic acid contents 1219:1243 high sialic acid contents 1219:1243 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 2 25 theme mean 400:403 arg1 values 408:413 The mean pI values 396:413 The mean pI values of the EPO fractions 396:434 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 2 26 theme IEF-gel 450:456 arg1 electrophoresis 458:472 IEF-gel electrophoresis 450:472 IEF-gel electrophoresis systematically shifted from 4.11 to 3.31 450:513 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 1 27 theme Q 371:371 arg1 chromatography 380:393 Mono Q column chromatography 366:393 Mono Q column chromatography 366:393 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 5 28 theme fractions 1059:1067 arg1 bioactivity 1039:1049 the in vivo bioactivity 1027:1049 the in vivo bioactivity of some fractions with low sialic acid contents 1027:1097 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 5 29 with treatment 1119:1127 arg1 2,6-sialyltransferase 1140:1160 alpha 2,6-sialyltransferase 1134:1160 alpha 2,6-sialyltransferase 1134:1160 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 5 30 theme in 1171:1172 arg1 bioactivity 1179:1189 the in vivo bioactivity 1167:1189 the in vivo bioactivity of the other fractions with high sialic acid contents 1167:1243 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 5 31 dep in 1031:1032 arg1 vivo 1034:1037 vivo 1034:1037 vivo 1034:1037 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 1 32 theme column 373:378 arg1 chromatography 380:393 Mono Q column chromatography 366:393 Mono Q column chromatography 366:393 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 2 33 theme oligosaccharides 613:628 arg1 constitution 581:592 the constitution 577:592 the constitution of asialo N-linked oligosaccharides of each fraction 577:645 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 3 34 theme fractionated 746:757 arg1 samples 759:765 the fractionated samples 742:765 the fractionated samples 742:765 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 1 35 dep kidney 321:326 arg1 EPO 359:361 cell-derived recombinant human EPO 328:361 baby hamster kidney cell-derived recombinant human EPO 308:361 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 0 36 theme Biological 0:9 arg1 characterization 31:46 Biological and physicochemical characterization 0:46 Biological and physicochemical characterization of recombinant human erythropoietins 0:83 Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase. 8981093 1 37 theme EPO 284:286 arg1 mol-1 275:279 9.5 to 13.8 mol mol-1 259:279 9.5 to 13.8 mol mol-1 of EPO 259:286 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 2 38 theme N-linked 604:611 arg1 oligosaccharides 613:628 asialo N-linked oligosaccharides 597:628 asialo N-linked oligosaccharides of each fraction 597:645 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 0 39 with chromatography 115:128 arg1 sialyltransferase 158:174 sialyltransferase 158:174 sialyltransferase 158:174 Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase. 8981093 3 40 from increase 830:837 arg1 activity 848:855 their activity 842:855 their activity 842:855 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 2 41 theme fractions 426:434 arg1 values 408:413 The mean pI values 396:413 The mean pI values of the EPO fractions 396:434 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 3 42 theme samples 759:765 arg1 relationship 666:677 a linear relationship 657:677 a linear relationship between the in vivo bioactivity 657:709 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 3 42 theme samples 759:765 arg1 content 731:737 the sialic acid content 715:737 the sialic acid content of the fractionated samples 715:765 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 1 43 theme sialic 225:230 arg1 acid 232:235 sialic acid 225:235 sialic acid content 225:243 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 0 44 theme physicochemical 15:29 arg1 characterization 31:46 Biological and physicochemical characterization 0:46 Biological and physicochemical characterization of recombinant human erythropoietins 0:83 Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase. 8981093 4 45 theme sialic 965:970 arg1 content 977:983 sialic acid content 965:983 sialic acid content of EPO 965:990 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 4 46 theme other 892:896 arg1 hand 898:901 the other hand 888:901 the other hand 888:901 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 1 47 link cell-derived 328:339 arg1 EPO 359:361 cell-derived recombinant human EPO 328:361 baby hamster kidney cell-derived recombinant human EPO 308:361 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 1 48 theme acid 232:235 arg1 content 237:243 sialic acid content 225:243 sialic acid content 225:243 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 0 49 theme recombinant 51:61 arg1 erythropoietins 69:83 recombinant human erythropoietins 51:83 recombinant human erythropoietins 51:83 Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase. 8981093 2 50 theme acid 543:546 arg1 content 548:554 the sialic acid content 532:554 the sialic acid content 532:554 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 5 51 theme acid 1231:1234 arg1 contents 1236:1243 high sialic acid contents 1219:1243 high sialic acid contents 1219:1243 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 4 52 theme in 940:941 arg1 bioactivity 949:959 the in vitro bioactivity 936:959 the in vitro bioactivity 936:959 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 2 53 theme sialic 536:541 arg1 content 548:554 the sialic acid content 532:554 the sialic acid content 532:554 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 2 54 theme pI 405:406 arg1 values 408:413 The mean pI values 396:413 The mean pI values of the EPO fractions 396:434 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 0 55 theme erythropoietins 69:83 arg1 characterization 31:46 Biological and physicochemical characterization 0:46 Biological and physicochemical characterization of recombinant human erythropoietins 0:83 Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase. 8981093 1 56 theme baby 308:311 arg1 kidney 321:326 baby hamster kidney cell-derived recombinant human EPO 308:361 baby hamster kidney cell-derived recombinant human EPO 308:361 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 5 57 dep in 1171:1172 arg1 vivo 1174:1177 vivo 1174:1177 vivo 1174:1177 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 0 58 theme human 63:67 arg1 erythropoietins 69:83 recombinant human erythropoietins 51:83 recombinant human erythropoietins 51:83 Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase. 8981093 1 59 theme hamster 313:319 arg1 kidney 321:326 baby hamster kidney cell-derived recombinant human EPO 308:361 baby hamster kidney cell-derived recombinant human EPO 308:361 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 4 60 dep in 940:941 arg1 vitro 943:947 vitro 943:947 vitro 943:947 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 5 61 theme sialic 1078:1083 arg1 contents 1090:1097 low sialic acid contents 1074:1097 low sialic acid contents 1074:1097 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 3 62 theme in 691:692 arg1 bioactivity 699:709 the in vivo bioactivity 687:709 the in vivo bioactivity 687:709 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 4 63 theme EPO 988:990 arg1 relationship 915:926 an inverse relationship 904:926 an inverse relationship between the in vitro bioactivity 904:959 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 4 63 theme EPO 988:990 arg1 content 977:983 sialic acid content 965:983 sialic acid content of EPO 965:990 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 3 64 theme mol 867:869 arg1 mol-1 871:875 12.4 mol mol-1 862:875 12.4 mol mol-1 of EPO 862:882 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 5 65 theme high 1219:1222 arg1 contents 1236:1243 high sialic acid contents 1219:1243 high sialic acid contents 1219:1243 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 1 66 dep 13.8 266:269 arg1 to 263:264 to 263:264 to 263:264 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 3 67 theme further 822:828 arg1 increase 830:837 no further increase 819:837 no further increase in their activity 819:855 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 3 68 theme EPO 804:806 arg1 mol-1 795:799 12.1 mol mol-1 786:799 12.1 mol mol-1 of EPO 786:806 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 5 69 with fractions 1059:1067 arg1 contents 1090:1097 low sialic acid contents 1074:1097 low sialic acid contents 1074:1097 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 8981093 0 70 with modification 140:151 arg1 sialyltransferase 158:174 sialyltransferase 158:174 sialyltransferase 158:174 Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase. 8981093 3 71 theme mol 791:793 arg1 mol-1 795:799 12.1 mol mol-1 786:799 12.1 mol mol-1 of EPO 786:806 Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. 8981093 4 72 theme acid 972:975 arg1 content 977:983 sialic acid content 965:983 sialic acid content of EPO 965:990 On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. 8981093 1 73 theme cell-derived 328:339 arg1 EPO 359:361 cell-derived recombinant human EPO 328:361 baby hamster kidney cell-derived recombinant human EPO 308:361 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 2 74 theme EPO 422:424 arg1 fractions 426:434 the EPO fractions 418:434 the EPO fractions 418:434 The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. 8981093 1 75 theme erythropoietin 181:194 arg1 fractions 202:210 Ten erythropoietin (EPO) fractions 177:210 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, 177:287 Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. 8981093 5 76 theme acid 1085:1088 arg1 contents 1090:1097 low sialic acid contents 1074:1097 low sialic acid contents 1074:1097 Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected. 34623376 0 0 theme SARS-related 103:114 arg1 viruses 116:122 SARS-related viruses 103:122 SARS-related viruses 103:122 Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses. 34623376 4 1 theme germinal 711:718 arg1 GC 728:729 GC 728:729 GC 728:729 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 4 1 theme germinal 711:718 arg1 center 720:725 the core-RBD-specific germinal center 689:725 the core-RBD-specific germinal center (GC) B cells 689:738 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 5 2 contain have 880:883 arg2 implications 885:896 implications 885:896 implications for the design of SARS-like virus vaccines 885:939 These results have implications for the design of SARS-like virus vaccines. 34623376 5 2 contain have 880:883 arg1 results 872:878 These results 866:878 These results 866:878 These results have implications for the design of SARS-like virus vaccines. 34623376 1 3 theme future 203:208 arg1 outbreaks 210:218 future outbreaks 203:218 future outbreaks 203:218 Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. 34623376 3 4 theme RBD 578:580 arg1 surfaces 551:558 RBM surfaces 547:558 RBM surfaces of the SARS-CoV-2 RBD 547:580 Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. 34623376 4 5 theme responses 753:761 arg1 proportions 674:684 higher proportions 667:684 higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses 667:761 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 4 6 theme core-RBD-specific 693:709 arg1 GC 728:729 GC 728:729 GC 728:729 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 4 6 theme core-RBD-specific 693:709 arg1 center 720:725 the core-RBD-specific germinal center 689:725 the core-RBD-specific germinal center (GC) B cells 689:738 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 3 7 theme RBM 547:549 arg1 surfaces 551:558 RBM surfaces 547:558 RBM surfaces of the SARS-CoV-2 RBD 547:580 Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. 34623376 5 8 theme virus 926:930 arg1 vaccines 932:939 SARS-like virus vaccines 916:939 SARS-like virus vaccines 916:939 These results have implications for the design of SARS-like virus vaccines. 34623376 3 9 theme humoral 461:467 arg1 responses 469:477 humoral responses 461:477 humoral responses to the more conserved core-RBD 461:508 Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. 34623376 4 10 theme cells 734:738 arg1 proportions 674:684 higher proportions 667:684 higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses 667:761 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 0 11 theme Glycan 0:5 arg1 engineering 7:17 Glycan engineering 0:17 Glycan engineering of the SARS-CoV-2 receptor-binding domain 0:59 Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses. 34623376 4 12 theme bat 852:854 arg1 WIV1-CoV 856:863 the bat WIV1-CoV 848:863 the bat WIV1-CoV 848:863 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 4 13 theme B 732:732 arg1 cells 734:738 the core-RBD-specific germinal center (GC) B cells 689:738 the core-RBD-specific germinal center (GC) B cells 689:738 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 4 14 theme higher 667:672 arg1 proportions 674:684 higher proportions 667:684 higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses 667:761 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 2 15 theme receptor-binding 336:351 arg1 RBM 360:362 RBM 360:362 RBM 360:362 The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. 34623376 2 15 theme receptor-binding 336:351 arg1 motif 353:357 the receptor-binding motif 332:357 the receptor-binding motif (RBM) 332:363 The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. 34623376 2 15 theme receptor-binding 336:351 arg1 regions 306:312 two regions 302:312 two regions 302:312 The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. 34623376 3 16 link N-linked 525:532 arg1 glycans 534:540 N-linked glycans 525:540 N-linked glycans 525:540 Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. 34623376 1 17 theme protective 133:142 arg1 vaccines 144:151 Broadly protective vaccines 125:151 Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks 125:218 Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. 34623376 3 18 from immunogens 599:608 arg1 model 621:625 a mouse model 613:625 a mouse model 613:625 Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. 34623376 0 19 theme receptor-binding 37:52 arg1 domain 54:59 the SARS-CoV-2 receptor-binding domain 22:59 the SARS-CoV-2 receptor-binding domain 22:59 Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses. 34623376 5 20 theme SARS-like 916:924 arg1 vaccines 932:939 SARS-like virus vaccines 916:939 SARS-like virus vaccines 916:939 These results have implications for the design of SARS-like virus vaccines. 34623376 4 21 theme glycan 642:647 arg1 addition 649:656 glycan addition 642:656 glycan addition 642:656 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 1 22 theme Broadly 125:131 arg1 vaccines 144:151 Broadly protective vaccines 125:151 Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks 125:218 Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. 34623376 3 23 used used 586:589 arg2 we 511:512 we 511:512 we 511:512 Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. 34623376 0 24 theme SARS-CoV-2 26:35 arg1 domain 54:59 the SARS-CoV-2 receptor-binding domain 22:59 the SARS-CoV-2 receptor-binding domain 22:59 Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses. 34623376 4 25 theme antibody 744:751 arg1 responses 753:761 antibody responses 744:761 antibody responses 744:761 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 0 26 theme domain 54:59 arg1 engineering 7:17 Glycan engineering 0:17 Glycan engineering of the SARS-CoV-2 receptor-binding domain 0:59 Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses. 34623376 2 27 theme spike 256:260 arg1 RBD 287:289 RBD 287:289 RBD 287:289 The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. 34623376 2 27 theme spike 256:260 arg1 domain 279:284 The SARS-CoV-2 spike receptor-binding domain 241:284 The SARS-CoV-2 spike receptor-binding domain (RBD) 241:290 The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. 34623376 2 28 theme receptor-binding 262:277 arg1 RBD 287:289 RBD 287:289 RBD 287:289 The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. 34623376 2 28 theme receptor-binding 262:277 arg1 domain 279:284 The SARS-CoV-2 spike receptor-binding domain 241:284 The SARS-CoV-2 spike receptor-binding domain (RBD) 241:290 The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. 34623376 3 29 theme N-linked 525:532 arg1 glycans 534:540 N-linked glycans 525:540 N-linked glycans 525:540 Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. 34623376 4 30 theme center 720:725 arg1 cells 734:738 the core-RBD-specific germinal center (GC) B cells 689:738 the core-RBD-specific germinal center (GC) B cells 689:738 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 2 31 theme SARS-CoV-2 245:254 arg1 RBD 287:289 RBD 287:289 RBD 287:289 The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. 34623376 2 31 theme SARS-CoV-2 245:254 arg1 domain 279:284 The SARS-CoV-2 spike receptor-binding domain 241:284 The SARS-CoV-2 spike receptor-binding domain (RBD) 241:290 The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. 34623376 4 32 theme neutralizing 796:807 arg1 activity 809:816 significant neutralizing activity 784:816 significant neutralizing activity 784:816 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 1 33 theme SARS-related 161:172 arg1 coronaviruses 174:186 SARS-related coronaviruses 161:186 SARS-related coronaviruses that may cause future outbreaks 161:218 Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. 34623376 3 34 theme SARS-CoV-2 567:576 arg1 RBD 578:580 the SARS-CoV-2 RBD 563:580 the SARS-CoV-2 RBD 563:580 Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. 34623376 4 35 theme significant 784:794 arg1 activity 809:816 significant neutralizing activity 784:816 significant neutralizing activity 784:816 We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. 34623376 5 36 theme vaccines 932:939 arg1 design 906:911 the design 902:911 the design of SARS-like virus vaccines 902:939 These results have implications for the design of SARS-like virus vaccines. 34623376 3 37 theme conserved 491:499 arg1 core-RBD 501:508 the more conserved core-RBD 482:508 the more conserved core-RBD 482:508 Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. 34623376 0 38 theme cross-neutralizing 69:86 arg1 antibodies 88:97 cross-neutralizing antibodies 69:97 cross-neutralizing antibodies for SARS-related viruses 69:122 Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses. 34623376 3 39 theme mouse 615:619 arg1 model 621:625 a mouse model 613:625 a mouse model 613:625 Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. 34133718 2 0 theme tumor 465:469 arg1 PCs 471:473 tumor PCs 465:473 tumor PCs 465:473 Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. 34133718 4 1 theme normal 867:872 arg1 PCs 874:876 normal PCs 867:876 normal PCs 867:876 Based on bulk and single-cell RNA sequencing, we observed 13 TPs during transition of normal PCs throughout SLOs, PB, and BM. 34133718 2 2 theme such 367:370 arg1 differences 372:382 such differences 367:382 such differences were unsuccessful 367:400 Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. 34133718 0 3 from cells 6:10 arg1 myeloma 43:49 myeloma 43:49 myeloma 43:49 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. 34133718 0 3 from cells 6:10 arg1 amyloidosis 27:37 light-chain amyloidosis 15:37 light-chain amyloidosis 15:37 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. 34133718 5 4 theme protein 1270:1276 arg1 TPs 1309:1311 protein N-linked glycosylation-related TPs 1270:1311 protein N-linked glycosylation-related TPs 1270:1311 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 3 5 theme monoclonal 722:731 arg1 MGUS 774:777 MGUS 774:777 MGUS 774:777 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 5 theme monoclonal 722:731 arg1 gammopathy 733:742 monoclonal gammopathy 722:742 monoclonal gammopathy of undetermined significance (MGUS) 722:778 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 0 6 theme plasma 100:105 arg1 development 112:122 normal plasma cell development 93:122 normal plasma cell development 93:122 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. 34133718 6 7 theme gammopathies 1480:1491 arg1 development 1402:1412 normal PC development 1392:1412 normal PC development 1392:1412 Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies. 34133718 6 7 theme gammopathies 1480:1491 arg1 reorganization 1438:1451 the transcriptional reorganization 1418:1451 the transcriptional reorganization of AL and other monoclonal gammopathies 1418:1491 Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies. 34133718 5 8 theme N-linked 1278:1285 arg1 TPs 1309:1311 protein N-linked glycosylation-related TPs 1270:1311 protein N-linked glycosylation-related TPs 1270:1311 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 5 9 theme PC 1065:1066 arg1 differentiation 1068:1082 normal PC differentiation 1058:1082 normal PC differentiation 1058:1082 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 0 10 theme normal 93:98 arg1 development 112:122 normal plasma cell development 93:122 normal plasma cell development 93:122 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. 34133718 3 11 with gammopathy 733:742 arg1 programs 679:686 the transcriptional programs 659:686 the transcriptional programs (TPs) of tumor PCs in AL 659:711 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 11 with gammopathy 733:742 arg1 TPs 689:691 TPs 689:691 TPs 689:691 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 6 12 theme AL 1456:1457 arg1 development 1402:1412 normal PC development 1392:1412 normal PC development 1392:1412 Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies. 34133718 6 12 theme AL 1456:1457 arg1 reorganization 1438:1451 the transcriptional reorganization 1418:1451 the transcriptional reorganization of AL and other monoclonal gammopathies 1418:1491 Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies. 34133718 5 13 theme glycosylation-related 1287:1307 arg1 TPs 1309:1311 protein N-linked glycosylation-related TPs 1270:1311 protein N-linked glycosylation-related TPs 1270:1311 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 1 14 dep amyloidosis 146:156 arg1 AL 159:160 AL 159:160 AL 159:160 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 6 15 theme PC 1399:1400 arg1 development 1402:1412 normal PC development 1392:1412 normal PC development 1392:1412 Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies. 34133718 5 16 link N-linked 1278:1285 arg1 TPs 1309:1311 protein N-linked glycosylation-related TPs 1270:1311 protein N-linked glycosylation-related TPs 1270:1311 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 0 17 theme development 112:122 arg1 rewiring 81:88 distinct transcriptional rewiring 56:88 distinct transcriptional rewiring of normal plasma cell development 56:122 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. 34133718 5 18 theme differentiation 1068:1082 arg1 TPs 1051:1053 the most advantageous TPs 1029:1053 the most advantageous TPs of normal PC differentiation 1029:1082 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 6 19 theme normal 1392:1397 arg1 development 1402:1412 normal PC development 1392:1412 normal PC development 1392:1412 Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies. 34133718 1 20 theme multiple 167:174 arg1 MM 185:186 MM 185:186 MM 185:186 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 1 20 theme multiple 167:174 arg1 myeloma 176:182 multiple myeloma 167:182 multiple myeloma (MM) 167:187 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 0 21 theme cell 107:110 arg1 development 112:122 normal plasma cell development 93:122 normal plasma cell development 93:122 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. 34133718 2 22 from stage 456:460 arg1 patients 478:485 patients 478:485 patients with AL and MM 478:500 Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. 34133718 5 23 theme inferior 1247:1254 arg1 survival 1256:1263 inferior survival 1247:1263 inferior survival 1247:1263 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 3 24 from programs 679:686 arg1 AL 710:711 AL 710:711 AL 710:711 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 2 25 with patients 478:485 arg1 MM 499:500 MM 499:500 MM 499:500 Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. 34133718 2 25 with patients 478:485 arg1 AL 492:493 AL 492:493 AL 492:493 Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. 34133718 5 26 dep following 928:936 arg1 outperforms 944:954 outperforms 944:954 outperforms CD19 to discriminate newborn from long-lived BM-PCs 944:1006 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 5 26 dep following 928:936 arg1 expressed 1019:1027 expressed 1019:1027 expressed the most advantageous TPs of normal PC differentiation 1019:1082 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 5 26 dep following 928:936 arg1 shares 1088:1093 shares 1088:1093 shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs 1088:1191 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 5 26 dep following 928:936 arg1 upregulated 1317:1327 upregulated 1317:1327 are upregulated in AL 1313:1333 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 5 26 dep following 928:936 arg1 had 1243:1245 had 1243:1245 had inferior survival 1243:1263 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 0 27 theme Tumor 0:4 arg1 cells 6:10 Tumor cells 0:10 Tumor cells in light-chain amyloidosis and myeloma 0:49 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. 34133718 1 28 theme bone 246:249 arg1 BM 259:260 BM 259:260 BM 259:260 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 1 28 theme bone 246:249 arg1 marrow 251:256 bone marrow 246:256 bone marrow (BM) 246:261 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 6 29 theme monoclonal 1469:1478 arg1 gammopathies 1480:1491 other monoclonal gammopathies 1463:1491 other monoclonal gammopathies 1463:1491 Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies. 34133718 3 30 theme transcriptional 525:539 arg1 atlas 541:545 a transcriptional atlas 523:545 a transcriptional atlas of normal PC development 523:570 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 5 31 theme long-lived 990:999 arg1 BM-PCs 1001:1006 long-lived BM-PCs 990:1006 long-lived BM-PCs 990:1006 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 2 32 theme pathogenic 338:347 arg1 mechanisms 349:358 unique pathogenic mechanisms 331:358 unique pathogenic mechanisms behind such differences were unsuccessful 331:400 Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. 34133718 0 33 theme light-chain 15:25 arg1 amyloidosis 27:37 light-chain amyloidosis 15:37 light-chain amyloidosis 15:37 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. 34133718 3 34 theme PCs 703:705 arg1 programs 679:686 the transcriptional programs 659:686 the transcriptional programs (TPs) of tumor PCs in AL 659:711 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 34 theme PCs 703:705 arg1 TPs 689:691 TPs 689:691 TPs 689:691 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 1 35 from expansion 233:241 arg1 BM 259:260 BM 259:260 BM 259:260 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 1 35 from expansion 233:241 arg1 marrow 251:256 bone marrow 246:256 bone marrow (BM) 246:261 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 6 36 theme other 1463:1467 arg1 gammopathies 1480:1491 other monoclonal gammopathies 1463:1491 other monoclonal gammopathies 1463:1491 Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies. 34133718 6 37 theme novel 1363:1367 arg1 resource 1369:1376 a novel resource 1361:1376 a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies 1361:1491 Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies. 34133718 5 38 theme advantageous 1038:1049 arg1 TPs 1051:1053 the most advantageous TPs 1029:1053 the most advantageous TPs of normal PC differentiation 1029:1082 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 4 39 theme single-cell 799:809 arg1 sequencing 815:824 single-cell RNA sequencing 799:824 single-cell RNA sequencing 799:824 Based on bulk and single-cell RNA sequencing, we observed 13 TPs during transition of normal PCs throughout SLOs, PB, and BM. 34133718 3 40 theme transcriptional 663:677 arg1 programs 679:686 the transcriptional programs 659:686 the transcriptional programs (TPs) of tumor PCs in AL 659:711 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 40 theme transcriptional 663:677 arg1 TPs 689:691 TPs 689:691 TPs 689:691 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 41 theme normal 550:555 arg1 development 560:570 normal PC development 550:570 normal PC development 550:570 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 5 42 theme newborn 1178:1184 arg1 BM-PCs 1186:1191 newborn BM-PCs 1178:1191 newborn BM-PCs 1178:1191 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 5 43 theme normal 1058:1063 arg1 differentiation 1068:1082 normal PC differentiation 1058:1082 normal PC differentiation 1058:1082 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 2 44 theme differentiation 440:454 arg1 stage 456:460 the differentiation stage 436:460 the differentiation stage of tumor PCs in patients with AL and MM 436:500 Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. 34133718 4 45 theme PCs 874:876 arg1 transition 853:862 transition 853:862 transition of normal PCs throughout SLOs, PB, and BM 853:904 Based on bulk and single-cell RNA sequencing, we observed 13 TPs during transition of normal PCs throughout SLOs, PB, and BM. 34133718 3 46 theme PC 557:558 arg1 development 560:570 normal PC development 550:570 normal PC development 550:570 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 47 with MM 714:715 arg1 programs 679:686 the transcriptional programs 659:686 the transcriptional programs (TPs) of tumor PCs in AL 659:711 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 47 with MM 714:715 arg1 TPs 689:691 TPs 689:691 TPs 689:691 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 48 theme tumor 697:701 arg1 PCs 703:705 tumor PCs 697:705 tumor PCs in AL 697:711 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 49 from PCs 703:705 arg1 AL 710:711 AL 710:711 AL 710:711 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 2 50 theme PCs 471:473 arg1 stage 456:460 the differentiation stage 436:460 the differentiation stage of tumor PCs in patients with AL and MM 436:500 Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. 34133718 5 51 theme immature 1230:1237 arg1 TPs 1239:1241 immature TPs 1230:1241 immature TPs 1230:1241 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 5 52 contain had 1243:1245 arg1 patients 1194:1201 patients 1194:1201 patients with AL and MM enriched in immature TPs 1194:1241 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 5 52 contain had 1243:1245 arg2 survival 1256:1263 inferior survival 1247:1263 inferior survival 1247:1263 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 4 53 theme RNA 811:813 arg1 sequencing 815:824 single-cell RNA sequencing 799:824 single-cell RNA sequencing 799:824 Based on bulk and single-cell RNA sequencing, we observed 13 TPs during transition of normal PCs throughout SLOs, PB, and BM. 34133718 5 54 with patients 1194:1201 arg1 MM 1215:1216 MM 1215:1216 MM enriched in immature TPs 1215:1241 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 5 54 with patients 1194:1201 arg1 AL 1208:1209 AL 1208:1209 AL 1208:1209 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 3 55 theme undetermined 747:758 arg1 significance 760:771 undetermined significance 747:771 undetermined significance 747:771 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 1 56 theme clinical 270:277 arg1 presentation 279:290 their clinical presentation 264:290 their clinical presentation 264:290 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 3 57 from AL 710:711 arg1 programs 679:686 the transcriptional programs 659:686 the transcriptional programs (TPs) of tumor PCs in AL 659:711 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 57 from AL 710:711 arg1 TPs 689:691 TPs 689:691 TPs 689:691 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 58 theme secondary 575:583 arg1 SLOs 602:605 SLOs 602:605 SLOs 602:605 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 58 theme secondary 575:583 arg1 organs 594:599 secondary lymphoid organs 575:599 secondary lymphoid organs (SLOs) 575:606 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 1 59 theme light-chain 134:144 arg1 amyloidosis 146:156 light-chain amyloidosis 134:156 light-chain amyloidosis (AL) 134:161 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 3 60 theme significance 760:771 arg1 MGUS 774:777 MGUS 774:777 MGUS 774:777 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 60 theme significance 760:771 arg1 gammopathy 733:742 monoclonal gammopathy 722:742 monoclonal gammopathy of undetermined significance (MGUS) 722:778 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 60 theme significance 760:771 arg1 comparison 643:652 comparison 643:652 comparison with the transcriptional programs (TPs) of tumor PCs in AL 643:711 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 60 theme significance 760:771 arg1 MM 714:715 MM 714:715 MM 714:715 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 1 61 theme tumor 210:214 arg1 cell 223:226 tumor plasma cell 210:226 tumor plasma cell (PC) expansion in bone marrow (BM) 210:261 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 1 61 theme tumor 210:214 arg1 PC 229:230 PC 229:230 PC 229:230 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 3 62 theme lymphoid 585:592 arg1 SLOs 602:605 SLOs 602:605 SLOs 602:605 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 62 theme lymphoid 585:592 arg1 organs 594:599 secondary lymphoid organs 575:599 secondary lymphoid organs (SLOs) 575:606 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 6 63 theme transcriptional 1422:1436 arg1 reorganization 1438:1451 the transcriptional reorganization 1418:1451 the transcriptional reorganization of AL and other monoclonal gammopathies 1418:1491 Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies. 34133718 3 64 with comparison 643:652 arg1 programs 679:686 the transcriptional programs 659:686 the transcriptional programs (TPs) of tumor PCs in AL 659:711 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 64 with comparison 643:652 arg1 TPs 689:691 TPs 689:691 TPs 689:691 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 1 65 theme plasma 216:221 arg1 cell 223:226 tumor plasma cell 210:226 tumor plasma cell (PC) expansion in bone marrow (BM) 210:261 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 1 65 theme plasma 216:221 arg1 PC 229:230 PC 229:230 PC 229:230 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 0 66 theme transcriptional 65:79 arg1 rewiring 81:88 distinct transcriptional rewiring 56:88 distinct transcriptional rewiring of normal plasma cell development 56:122 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. 34133718 3 67 theme peripheral 609:618 arg1 PB 627:628 PB 627:628 PB 627:628 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 67 theme peripheral 609:618 arg1 blood 620:624 peripheral blood 609:624 peripheral blood (PB) 609:629 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 3 68 theme development 560:570 arg1 atlas 541:545 a transcriptional atlas 523:545 a transcriptional atlas of normal PC development 523:570 We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). 34133718 2 69 theme unique 331:336 arg1 mechanisms 349:358 unique pathogenic mechanisms 331:358 unique pathogenic mechanisms behind such differences were unsuccessful 331:400 Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. 34133718 1 70 theme cell 223:226 arg1 expansion 233:241 tumor plasma cell (PC) expansion 210:241 tumor plasma cell (PC) expansion in bone marrow (BM) 210:261 Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. 34133718 0 71 theme distinct 56:63 arg1 rewiring 81:88 distinct transcriptional rewiring 56:88 distinct transcriptional rewiring of normal plasma cell development 56:122 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. 34133718 5 72 theme greater 1095:1101 arg1 similarity 1103:1112 greater similarity 1095:1112 greater similarity to SLO-PCs 1095:1123 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34133718 5 73 theme tumor 1009:1013 arg1 PCs 1015:1017 tumor PCs 1009:1017 tumor PCs 1009:1017 We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation-related TPs are upregulated in AL. 34855508 1 0 theme respiratory 145:155 arg1 coronavirus 166:176 severe acute respiratory syndrome coronavirus 2 132:178 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants 132:200 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 1 0 theme respiratory 145:155 arg1 SARS-CoV-2 181:190 SARS-CoV-2 181:190 SARS-CoV-2 181:190 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 0 1 theme binding 75:81 arg1 domain 83:88 the SARS-CoV-2 receptor binding domain 51:88 the SARS-CoV-2 receptor binding domain 51:88 Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain. 34855508 1 2 theme syndrome 157:164 arg1 coronavirus 166:176 severe acute respiratory syndrome coronavirus 2 132:178 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants 132:200 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 1 2 theme syndrome 157:164 arg1 SARS-CoV-2 181:190 SARS-CoV-2 181:190 SARS-CoV-2 181:190 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 3 3 contain containing 520:529 arg1 pseudotypes 508:518 pseudotypes 508:518 pseudotypes 508:518 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 3 contain containing 520:529 arg2 mutations 543:551 up to seven mutations 531:551 up to seven mutations 531:551 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 1 4 theme dominant 259:266 arg1 strains 268:274 dominant strains 259:274 dominant strains 259:274 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 3 5 theme vaccine 712:718 arg1 recipients 720:729 vaccine recipients 712:729 vaccine recipients 712:729 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 5 6 theme escape 953:958 arg1 variants 960:967 escape variants 953:967 escape variants 953:967 Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans. 34855508 3 7 theme mutations 484:492 arg1 numbers 444:450 large numbers 438:450 large numbers of simultaneous antibody escape mutations 438:492 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 4 8 link N-linked 867:874 arg1 glycan 876:881 an N-linked glycan 864:881 an N-linked glycan to escape neutralization 864:906 We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. 34855508 3 9 theme antibody 468:475 arg1 mutations 484:492 simultaneous antibody escape mutations 455:492 simultaneous antibody escape mutations 455:492 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 5 10 theme variants 960:967 arg1 emergence 940:948 continued emergence 930:948 continued emergence of escape variants 930:967 Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans. 34855508 5 10 theme variants 960:967 arg1 adapts 983:988 SARS-CoV-2 adapts 972:988 SARS-CoV-2 adapts to humans 972:998 Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans. 34855508 1 11 theme coronavirus 166:176 arg1 variants 193:200 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants 132:200 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants 132:200 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 1 12 from impact 122:127 arg1 activity 227:234 neutralizing antibody activity 205:234 neutralizing antibody activity 205:234 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 3 13 theme receptor 395:402 arg1 domain 412:417 the SARS-CoV-2 receptor binding domain 380:417 the SARS-CoV-2 receptor binding domain (RBD) 380:423 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 13 theme receptor 395:402 arg1 RBD 420:422 RBD 420:422 RBD 420:422 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 14 theme large 438:442 arg1 numbers 444:450 large numbers 438:450 large numbers of simultaneous antibody escape mutations 438:492 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 15 theme SARS-CoV-2 384:393 arg1 domain 412:417 the SARS-CoV-2 receptor binding domain 380:417 the SARS-CoV-2 receptor binding domain (RBD) 380:423 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 15 theme SARS-CoV-2 384:393 arg1 RBD 420:422 RBD 420:422 RBD 420:422 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 16 dep three 579:583 arg1 to 576:577 to 576:577 to 576:577 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 0 17 theme Structural 0:9 arg1 basis 11:15 Structural basis 0:15 Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain 0:88 Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain. 34855508 1 18 theme Many 91:94 arg1 studies 96:102 Many studies 91:102 Many studies 91:102 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 0 19 theme continued 21:29 arg1 evasion 40:46 continued antibody evasion 21:46 continued antibody evasion by the SARS-CoV-2 receptor binding domain 21:88 Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain. 34855508 5 20 theme continued 930:938 arg1 emergence 940:948 continued emergence 930:948 continued emergence of escape variants 930:967 Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans. 34855508 5 20 theme continued 930:938 arg1 adapts 983:988 SARS-CoV-2 adapts 972:988 SARS-CoV-2 adapts to humans 972:998 Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans. 34855508 3 21 theme simultaneous 455:466 arg1 mutations 484:492 simultaneous antibody escape mutations 455:492 simultaneous antibody escape mutations 455:492 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 22 from recipients 720:729 arg1 antibodies 686:695 therapeutic antibodies 674:695 therapeutic antibodies 674:695 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 22 from recipients 720:729 arg1 serum 701:705 serum 701:705 serum from vaccine recipients 701:729 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 1 23 theme variants 193:200 arg1 impact 122:127 the impact 118:127 the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity 118:234 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 3 24 dep seven 537:541 arg1 to 534:535 to 534:535 to 534:535 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 0 25 theme antibody 31:38 arg1 evasion 40:46 continued antibody evasion 21:46 continued antibody evasion by the SARS-CoV-2 receptor binding domain 21:88 Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain. 34855508 1 26 theme neutralizing 205:216 arg1 activity 227:234 neutralizing antibody activity 205:234 neutralizing antibody activity 205:234 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 3 27 theme binding 404:410 arg1 domain 412:417 the SARS-CoV-2 receptor binding domain 380:417 the SARS-CoV-2 receptor binding domain (RBD) 380:423 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 27 theme binding 404:410 arg1 RBD 420:422 RBD 420:422 RBD 420:422 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 4 28 theme N-linked 867:874 arg1 glycan 876:881 an N-linked glycan 864:881 an N-linked glycan to escape neutralization 864:906 We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. 34855508 3 29 theme concern 625:631 arg1 variants 613:620 previously studied variants 594:620 previously studied variants of concern 594:631 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 4 30 theme tested 814:819 arg1 variants 821:828 all tested variants 810:828 all tested variants 810:828 We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. 34855508 3 31 theme therapeutic 674:684 arg1 antibodies 686:695 therapeutic antibodies 674:695 therapeutic antibodies 674:695 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 32 dep pseudotypes 508:518 arg1 opposed 557:563 opposed 557:563 opposed to the one to three found in previously studied variants of concern 557:631 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 2 33 theme evolution 329:337 arg1 consequences 299:310 the consequences 295:310 the consequences of further viral evolution 295:337 Here, we evaluate the consequences of further viral evolution. 34855508 5 34 theme SARS-CoV-2 972:981 arg1 emergence 940:948 continued emergence 930:948 continued emergence of escape variants 930:967 Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans. 34855508 5 34 theme SARS-CoV-2 972:981 arg1 adapts 983:988 SARS-CoV-2 adapts 972:988 SARS-CoV-2 adapts to humans 972:998 Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans. 34855508 3 35 theme studied 605:611 arg1 variants 613:620 previously studied variants 594:620 previously studied variants of concern 594:631 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 2 36 theme viral 323:327 arg1 evolution 329:337 further viral evolution 315:337 further viral evolution 315:337 Here, we evaluate the consequences of further viral evolution. 34855508 1 37 theme antibody 218:225 arg1 activity 227:234 neutralizing antibody activity 205:234 neutralizing antibody activity 205:234 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 4 38 theme RBD 771:773 arg1 core 775:778 the RBD core 767:778 the RBD core 767:778 We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. 34855508 2 39 theme further 315:321 arg1 evolution 329:337 further viral evolution 315:337 further viral evolution 315:337 Here, we evaluate the consequences of further viral evolution. 34855508 3 40 theme escape 477:482 arg1 mutations 484:492 simultaneous antibody escape mutations 455:492 simultaneous antibody escape mutations 455:492 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 0 41 theme receptor 66:73 arg1 domain 83:88 the SARS-CoV-2 receptor binding domain 51:88 the SARS-CoV-2 receptor binding domain 51:88 Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain. 34855508 1 42 theme severe 132:137 arg1 coronavirus 166:176 severe acute respiratory syndrome coronavirus 2 132:178 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants 132:200 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 1 42 theme severe 132:137 arg1 SARS-CoV-2 181:190 SARS-CoV-2 181:190 SARS-CoV-2 181:190 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 0 43 theme SARS-CoV-2 55:64 arg1 domain 83:88 the SARS-CoV-2 receptor binding domain 51:88 the SARS-CoV-2 receptor binding domain 51:88 Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain. 34855508 1 44 theme acute 139:143 arg1 coronavirus 166:176 severe acute respiratory syndrome coronavirus 2 132:178 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants 132:200 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 1 44 theme acute 139:143 arg1 SARS-CoV-2 181:190 SARS-CoV-2 181:190 SARS-CoV-2 181:190 Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. 34855508 3 45 located found 585:589 arg2 three 579:583 three 579:583 three 579:583 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 34855508 3 45 located found 585:589 arg1 variants 613:620 previously studied variants 594:620 previously studied variants of concern 594:631 We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. 36356299 3 0 theme patient 474:480 arg1 levels 492:497 patient plasma at levels 474:497 patient plasma at levels up to 160ng/mL 474:512 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 4 1 theme Plasma 542:547 arg1 CALR 556:559 Plasma mutant CALR 542:559 Plasma mutant CALR 542:559 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 1 2 theme neoplasms 276:284 arg1 development 242:252 the development 238:252 the development of myeloproliferative neoplasms (MPNs) 238:291 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 10 3 theme mutant 1486:1491 arg1 proteins 1498:1505 secreted mutant CALR proteins 1477:1505 secreted mutant CALR proteins 1477:1505 Thus, secreted mutant CALR proteins will act more specifically on the MPN clone. 36356299 1 4 theme exon 176:179 arg1 mutation 155:162 a -1/+2 frameshifting mutation 133:162 a -1/+2 frameshifting mutation of the CALR exon 9 133:181 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 5 5 theme CALR-mutated 813:824 arg1 patients 826:833 CALR-mutated patients 813:833 CALR-mutated patients where they drive Tpo-independent colony formation 813:883 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 8 6 contain carry 1265:1269 arg2 TpoR 1271:1274 TpoR 1271:1274 TpoR 1271:1274 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 8 6 contain carry 1265:1269 arg1 cells 1249:1253 cells 1249:1253 cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma 1249:1356 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 8 7 theme CALR 1211:1214 arg1 proteins 1223:1230 exogenous CALR mutant proteins 1201:1230 exogenous CALR mutant proteins 1201:1230 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 2 8 theme Mutant 294:299 arg1 CALRs 301:305 Mutant CALRs 294:305 Mutant CALRs 294:305 Mutant CALRs were shown to interact with and activate the thrombopoietin receptor (TpoR/MPL) in the same cell. 36356299 9 9 theme mutated 1388:1394 arg1 cells 1396:1400 CALR mutated cells 1383:1400 CALR mutated cells exposing at the cell-surface TpoR carrying immature N-linked sugars 1383:1468 This is consistent with CALR mutated cells exposing at the cell-surface TpoR carrying immature N-linked sugars. 36356299 4 10 theme soluble 586:592 arg1 Receptor 606:613 soluble Transferrin Receptor 1 586:615 soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life 586:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 10 theme soluble 586:592 arg1 sTFRC 618:622 sTFRC 618:622 sTFRC 618:622 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 10 theme soluble 586:592 arg1 half-life 682:690 CALR mutant half-life 670:690 CALR mutant half-life 670:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 10 theme soluble 586:592 arg1 protein 648:654 a carrier protein 638:654 a carrier protein 638:654 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 7 11 theme mutant 1027:1032 arg1 proteins 1039:1046 mutant CALR proteins 1027:1046 mutant CALR proteins produced in one cell 1027:1067 By bioluminescence resonance energy transfer assay, we show that mutant CALR proteins produced in one cell can specifically interact in trans with the TpoR on a target cell. 36356299 7 12 theme energy 991:996 arg1 transfer 998:1005 bioluminescence resonance energy transfer 965:1005 bioluminescence resonance energy transfer assay 965:1011 By bioluminescence resonance energy transfer assay, we show that mutant CALR proteins produced in one cell can specifically interact in trans with the TpoR on a target cell. 36356299 1 13 theme amino-acid 208:217 arg1 sequence 219:226 a novel C-terminal amino-acid sequence 189:226 a novel C-terminal amino-acid sequence 189:226 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 8 14 theme mutant 1167:1172 arg1 CALR 1174:1177 mutant CALR 1167:1177 mutant CALR 1167:1177 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 3 15 theme 25.64ng/mL 530:539 arg1 mean 522:525 a mean 520:525 a mean of 25.64ng/mL 520:539 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 7 16 theme bioluminescence 965:979 arg1 transfer 998:1005 bioluminescence resonance energy transfer 965:1005 bioluminescence resonance energy transfer assay 965:1011 By bioluminescence resonance energy transfer assay, we show that mutant CALR proteins produced in one cell can specifically interact in trans with the TpoR on a target cell. 36356299 5 17 theme colony 868:873 arg1 formation 875:883 Tpo-independent colony formation 852:883 Tpo-independent colony formation 852:883 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 8 18 theme mutant 1307:1312 arg1 proteins 1314:1321 CALR mutant proteins 1302:1321 CALR mutant proteins similar to those in patient plasma 1302:1356 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 8 19 contain carry 1147:1151 arg2 CALR 1174:1177 mutant CALR 1167:1177 mutant CALR 1167:1177 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 8 19 contain carry 1147:1151 arg2 TpoR 1158:1161 TpoR 1158:1161 TpoR 1158:1161 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 8 19 contain carry 1147:1151 arg1 Cells 1136:1140 Cells 1136:1140 Cells that carry both TpoR and mutant CALR 1136:1177 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 3 20 located found 465:469 arg1 levels 492:497 patient plasma at levels 474:497 patient plasma at levels up to 160ng/mL 474:512 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 3 20 located found 465:469 arg2 proteins 432:439 mutant CALR proteins 420:439 mutant CALR proteins 420:439 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 3 21 dep 160ng/mL 505:512 arg1 up 499:500 up 499:500 up 499:500 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 9 22 theme immature 1445:1452 arg1 sugars 1463:1468 immature N-linked sugars 1445:1468 immature N-linked sugars 1445:1468 This is consistent with CALR mutated cells exposing at the cell-surface TpoR carrying immature N-linked sugars. 36356299 5 23 theme mutant 705:710 arg1 proteins 717:724 Recombinant mutant CALR proteins 693:724 Recombinant mutant CALR proteins 693:724 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 7 24 from TpoR 1113:1116 arg1 cell 1130:1133 a target cell 1121:1133 a target cell 1121:1133 By bioluminescence resonance energy transfer assay, we show that mutant CALR proteins produced in one cell can specifically interact in trans with the TpoR on a target cell. 36356299 4 25 theme CALR 670:673 arg1 Receptor 606:613 soluble Transferrin Receptor 1 586:615 soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life 586:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 25 theme CALR 670:673 arg1 half-life 682:690 CALR mutant half-life 670:690 CALR mutant half-life 670:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 25 theme CALR 670:673 arg1 protein 648:654 a carrier protein 638:654 a carrier protein 638:654 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 11 26 theme gene 1658:1661 arg1 mutation 1633:1640 somatic mutation 1625:1640 somatic mutation of its encoding gene 1625:1661 In conclusion, a chaperone, CALR, can turn into a rogue cytokine through somatic mutation of its encoding gene. 36356299 5 27 from TpoR 750:753 arg1 progenitors 796:806 primary megakaryocytic progenitors 773:806 primary megakaryocytic progenitors 773:806 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 5 27 from TpoR 750:753 arg1 lines 763:767 cell lines 758:767 cell lines 758:767 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 5 28 from patients 826:833 arg1 progenitors 796:806 primary megakaryocytic progenitors 773:806 primary megakaryocytic progenitors 773:806 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 5 28 from patients 826:833 arg1 lines 763:767 cell lines 758:767 cell lines 758:767 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 6 29 theme TpoR 945:948 arg1 activation 950:959 TpoR activation 945:959 TpoR activation 945:959 Importantly, the CALR-sTFRC complex remains functional for TpoR activation. 36356299 1 30 theme calreticulin 89:100 arg1 proteins 109:116 Mutant calreticulin (CALR) proteins 82:116 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 82:181 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 1 31 theme -1/+2 135:139 arg1 mutation 155:162 a -1/+2 frameshifting mutation 133:162 a -1/+2 frameshifting mutation of the CALR exon 9 133:181 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 4 32 theme mutant 675:680 arg1 Receptor 606:613 soluble Transferrin Receptor 1 586:615 soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life 586:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 32 theme mutant 675:680 arg1 half-life 682:690 CALR mutant half-life 670:690 CALR mutant half-life 670:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 32 theme mutant 675:680 arg1 protein 648:654 a carrier protein 638:654 a carrier protein 638:654 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 3 33 theme at 489:490 arg1 levels 492:497 patient plasma at levels 474:497 patient plasma at levels up to 160ng/mL 474:512 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 3 34 theme CALR 427:430 arg1 proteins 432:439 mutant CALR proteins 420:439 mutant CALR proteins 420:439 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 8 35 theme similar 1323:1329 arg1 proteins 1314:1321 CALR mutant proteins 1302:1321 CALR mutant proteins similar to those in patient plasma 1302:1356 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 2 36 theme same 394:397 arg1 cell 399:402 the same cell 390:402 the same cell 390:402 Mutant CALRs were shown to interact with and activate the thrombopoietin receptor (TpoR/MPL) in the same cell. 36356299 5 37 theme megakaryocytic 781:794 arg1 progenitors 796:806 primary megakaryocytic progenitors 773:806 primary megakaryocytic progenitors 773:806 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 0 38 theme Rogue 33:37 arg1 Calreticulins 16:28 Mutant Calreticulins 9:28 Mutant Calreticulins 9:28 Secreted Mutant Calreticulins As Rogue Cytokines in Myeloproliferative Neoplasms. 36356299 0 38 theme Rogue 33:37 arg1 Cytokines 39:47 Rogue Cytokines 33:47 Rogue Cytokines in Myeloproliferative Neoplasms 33:79 Secreted Mutant Calreticulins As Rogue Cytokines in Myeloproliferative Neoplasms. 36356299 9 39 with consistent 1367:1376 arg1 cells 1396:1400 CALR mutated cells 1383:1400 CALR mutated cells exposing at the cell-surface TpoR carrying immature N-linked sugars 1383:1468 This is consistent with CALR mutated cells exposing at the cell-surface TpoR carrying immature N-linked sugars. 36356299 11 40 theme somatic 1625:1631 arg1 mutation 1633:1640 somatic mutation 1625:1640 somatic mutation of its encoding gene 1625:1661 In conclusion, a chaperone, CALR, can turn into a rogue cytokine through somatic mutation of its encoding gene. 36356299 8 41 theme patient 1343:1349 arg1 plasma 1351:1356 patient plasma 1343:1356 patient plasma 1343:1356 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 4 42 theme mutant 549:554 arg1 CALR 556:559 Plasma mutant CALR 542:559 Plasma mutant CALR 542:559 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 10 43 theme secreted 1477:1484 arg1 proteins 1498:1505 secreted mutant CALR proteins 1477:1505 secreted mutant CALR proteins 1477:1505 Thus, secreted mutant CALR proteins will act more specifically on the MPN clone. 36356299 3 44 theme plasma 482:487 arg1 levels 492:497 patient plasma at levels 474:497 patient plasma at levels up to 160ng/mL 474:512 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 1 45 theme myeloproliferative 257:274 arg1 MPNs 287:290 MPNs 287:290 MPNs 287:290 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 1 45 theme myeloproliferative 257:274 arg1 neoplasms 276:284 myeloproliferative neoplasms 257:284 myeloproliferative neoplasms (MPNs) 257:291 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 10 46 theme CALR 1493:1496 arg1 proteins 1498:1505 secreted mutant CALR proteins 1477:1505 secreted mutant CALR proteins 1477:1505 Thus, secreted mutant CALR proteins will act more specifically on the MPN clone. 36356299 1 47 theme CALR 171:174 arg1 exon 176:179 the CALR exon 9 167:181 the CALR exon 9 167:181 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 4 48 theme Transferrin 594:604 arg1 Receptor 606:613 soluble Transferrin Receptor 1 586:615 soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life 586:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 48 theme Transferrin 594:604 arg1 sTFRC 618:622 sTFRC 618:622 sTFRC 618:622 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 48 theme Transferrin 594:604 arg1 half-life 682:690 CALR mutant half-life 670:690 CALR mutant half-life 670:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 48 theme Transferrin 594:604 arg1 protein 648:654 a carrier protein 638:654 a carrier protein 638:654 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 2 49 from receptor 367:374 arg1 cell 399:402 the same cell 390:402 the same cell 390:402 Mutant CALRs were shown to interact with and activate the thrombopoietin receptor (TpoR/MPL) in the same cell. 36356299 7 50 theme CALR 1034:1037 arg1 proteins 1039:1046 mutant CALR proteins 1027:1046 mutant CALR proteins produced in one cell 1027:1067 By bioluminescence resonance energy transfer assay, we show that mutant CALR proteins produced in one cell can specifically interact in trans with the TpoR on a target cell. 36356299 5 51 theme cell 758:761 arg1 lines 763:767 cell lines 758:767 cell lines 758:767 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 8 52 theme exogenous 1201:1209 arg1 proteins 1223:1230 exogenous CALR mutant proteins 1201:1230 exogenous CALR mutant proteins 1201:1230 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 1 53 theme C-terminal 197:206 arg1 sequence 219:226 a novel C-terminal amino-acid sequence 189:226 a novel C-terminal amino-acid sequence 189:226 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 6 54 theme CALR-sTFRC 903:912 arg1 complex 914:920 the CALR-sTFRC complex 899:920 the CALR-sTFRC complex 899:920 Importantly, the CALR-sTFRC complex remains functional for TpoR activation. 36356299 8 55 theme mutant 1216:1221 arg1 proteins 1223:1230 exogenous CALR mutant proteins 1201:1230 exogenous CALR mutant proteins 1201:1230 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 10 56 theme MPN 1541:1543 arg1 clone 1545:1549 the MPN clone 1537:1549 the MPN clone 1537:1549 Thus, secreted mutant CALR proteins will act more specifically on the MPN clone. 36356299 7 57 theme transfer 998:1005 arg1 assay 1007:1011 bioluminescence resonance energy transfer assay 965:1011 bioluminescence resonance energy transfer assay 965:1011 By bioluminescence resonance energy transfer assay, we show that mutant CALR proteins produced in one cell can specifically interact in trans with the TpoR on a target cell. 36356299 5 58 theme Tpo-independent 852:866 arg1 formation 875:883 Tpo-independent colony formation 852:883 Tpo-independent colony formation 852:883 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 7 59 theme resonance 981:989 arg1 transfer 998:1005 bioluminescence resonance energy transfer 965:1005 bioluminescence resonance energy transfer assay 965:1011 By bioluminescence resonance energy transfer assay, we show that mutant CALR proteins produced in one cell can specifically interact in trans with the TpoR on a target cell. 36356299 9 60 theme cell-surface 1418:1429 arg1 TpoR 1431:1434 the cell-surface TpoR 1414:1434 the cell-surface TpoR carrying immature N-linked sugars 1414:1468 This is consistent with CALR mutated cells exposing at the cell-surface TpoR carrying immature N-linked sugars. 36356299 4 61 theme carrier 640:646 arg1 Receptor 606:613 soluble Transferrin Receptor 1 586:615 soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life 586:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 61 theme carrier 640:646 arg1 half-life 682:690 CALR mutant half-life 670:690 CALR mutant half-life 670:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 61 theme carrier 640:646 arg1 protein 648:654 a carrier protein 638:654 a carrier protein 638:654 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 11 62 theme encoding 1649:1656 arg1 gene 1658:1661 its encoding gene 1645:1661 its encoding gene 1645:1661 In conclusion, a chaperone, CALR, can turn into a rogue cytokine through somatic mutation of its encoding gene. 36356299 1 63 theme frameshifting 141:153 arg1 mutation 155:162 a -1/+2 frameshifting mutation 133:162 a -1/+2 frameshifting mutation of the CALR exon 9 133:181 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 3 64 from levels 492:497 arg1 patient 474:480 patient plasma at levels 474:497 patient plasma at levels up to 160ng/mL 474:512 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 3 64 from levels 492:497 arg1 plasma 482:487 patient plasma at levels 474:497 patient plasma at levels up to 160ng/mL 474:512 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 3 64 from levels 492:497 arg1 at 489:490 patient plasma at levels 474:497 patient plasma at levels up to 160ng/mL 474:512 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 5 65 theme Recombinant 693:703 arg1 proteins 717:724 Recombinant mutant CALR proteins 693:724 Recombinant mutant CALR proteins 693:724 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 9 66 theme N-linked 1454:1461 arg1 sugars 1463:1468 immature N-linked sugars 1445:1468 immature N-linked sugars 1445:1468 This is consistent with CALR mutated cells exposing at the cell-surface TpoR carrying immature N-linked sugars. 36356299 4 67 with complex 573:579 arg1 Receptor 606:613 soluble Transferrin Receptor 1 586:615 soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life 586:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 67 with complex 573:579 arg1 sTFRC 618:622 sTFRC 618:622 sTFRC 618:622 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 67 with complex 573:579 arg1 half-life 682:690 CALR mutant half-life 670:690 CALR mutant half-life 670:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 67 with complex 573:579 arg1 protein 648:654 a carrier protein 638:654 a carrier protein 638:654 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 11 68 from turn 1590:1593 arg1 conclusion 1555:1564 conclusion 1555:1564 conclusion 1555:1564 In conclusion, a chaperone, CALR, can turn into a rogue cytokine through somatic mutation of its encoding gene. 36356299 1 69 theme novel 191:195 arg1 sequence 219:226 a novel C-terminal amino-acid sequence 189:226 a novel C-terminal amino-acid sequence 189:226 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 1 70 theme Mutant 82:87 arg1 proteins 109:116 Mutant calreticulin (CALR) proteins 82:116 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 82:181 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 0 71 from Cytokines 39:47 arg1 Neoplasms 71:79 Myeloproliferative Neoplasms 52:79 Myeloproliferative Neoplasms 52:79 Secreted Mutant Calreticulins As Rogue Cytokines in Myeloproliferative Neoplasms. 36356299 3 72 theme mutant 420:425 arg1 proteins 432:439 mutant CALR proteins 420:439 mutant CALR proteins 420:439 We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160ng/mL, with a mean of 25.64ng/mL. 36356299 0 73 theme Mutant 9:14 arg1 Calreticulins 16:28 Mutant Calreticulins 9:28 Mutant Calreticulins 9:28 Secreted Mutant Calreticulins As Rogue Cytokines in Myeloproliferative Neoplasms. 36356299 0 73 theme Mutant 9:14 arg1 Cytokines 39:47 Rogue Cytokines 33:47 Rogue Cytokines in Myeloproliferative Neoplasms 33:79 Secreted Mutant Calreticulins As Rogue Cytokines in Myeloproliferative Neoplasms. 36356299 9 74 link N-linked 1454:1461 arg1 sugars 1463:1468 immature N-linked sugars 1445:1468 immature N-linked sugars 1445:1468 This is consistent with CALR mutated cells exposing at the cell-surface TpoR carrying immature N-linked sugars. 36356299 1 75 contain carry 183:187 arg2 sequence 219:226 a novel C-terminal amino-acid sequence 189:226 a novel C-terminal amino-acid sequence 189:226 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 1 75 contain carry 183:187 arg1 proteins 109:116 Mutant calreticulin (CALR) proteins 82:116 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 82:181 Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino-acid sequence and drive the development of myeloproliferative neoplasms (MPNs). 36356299 8 76 theme CALR 1302:1305 arg1 proteins 1314:1321 CALR mutant proteins 1302:1321 CALR mutant proteins similar to those in patient plasma 1302:1356 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 5 77 theme CALR 712:715 arg1 proteins 717:724 Recombinant mutant CALR proteins 693:724 Recombinant mutant CALR proteins 693:724 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 8 78 theme proteins 1314:1321 arg1 levels 1292:1297 levels 1292:1297 levels of CALR mutant proteins similar to those in patient plasma 1292:1356 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 0 79 theme Myeloproliferative 52:69 arg1 Neoplasms 71:79 Myeloproliferative Neoplasms 52:79 Myeloproliferative Neoplasms 52:79 Secreted Mutant Calreticulins As Rogue Cytokines in Myeloproliferative Neoplasms. 36356299 4 80 located found 564:568 arg2 CALR 556:559 Plasma mutant CALR 542:559 Plasma mutant CALR 542:559 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 4 80 located found 564:568 arg1 complex 573:579 complex 573:579 complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life 573:690 Plasma mutant CALR is found in complex with soluble Transferrin Receptor 1 (sTFRC) that acts as a carrier protein and increases CALR mutant half-life. 36356299 8 81 dep cells 1249:1253 arg1 comparison 1235:1244 comparison 1235:1244 comparison 1235:1244 Cells that carry both TpoR and mutant CALR are hypersensitive to exogenous CALR mutant proteins in comparison to cells that only carry TpoR, and respond to levels of CALR mutant proteins similar to those in patient plasma. 36356299 9 82 contain carrying 1436:1443 arg2 sugars 1463:1468 immature N-linked sugars 1445:1468 immature N-linked sugars 1445:1468 This is consistent with CALR mutated cells exposing at the cell-surface TpoR carrying immature N-linked sugars. 36356299 9 82 contain carrying 1436:1443 arg1 TpoR 1431:1434 the cell-surface TpoR 1414:1434 the cell-surface TpoR carrying immature N-linked sugars 1414:1468 This is consistent with CALR mutated cells exposing at the cell-surface TpoR carrying immature N-linked sugars. 36356299 11 83 theme rogue 1602:1606 arg1 cytokine 1608:1615 a rogue cytokine 1600:1615 a rogue cytokine through somatic mutation of its encoding gene 1600:1661 In conclusion, a chaperone, CALR, can turn into a rogue cytokine through somatic mutation of its encoding gene. 36356299 2 84 theme thrombopoietin 352:365 arg1 TpoR/MPL 377:384 TpoR/MPL 377:384 TpoR/MPL 377:384 Mutant CALRs were shown to interact with and activate the thrombopoietin receptor (TpoR/MPL) in the same cell. 36356299 2 84 theme thrombopoietin 352:365 arg1 receptor 367:374 the thrombopoietin receptor 348:374 the thrombopoietin receptor (TpoR/MPL) in the same cell 348:402 Mutant CALRs were shown to interact with and activate the thrombopoietin receptor (TpoR/MPL) in the same cell. 36356299 5 85 theme primary 773:779 arg1 progenitors 796:806 primary megakaryocytic progenitors 773:806 primary megakaryocytic progenitors 773:806 Recombinant mutant CALR proteins bound and activated the TpoR on cell lines and primary megakaryocytic progenitors from CALR-mutated patients where they drive Tpo-independent colony formation. 36356299 7 86 theme target 1123:1128 arg1 cell 1130:1133 a target cell 1121:1133 a target cell 1121:1133 By bioluminescence resonance energy transfer assay, we show that mutant CALR proteins produced in one cell can specifically interact in trans with the TpoR on a target cell. 34855475 0 0 theme lower 71:75 arg1 LDL 77:79 lower LDL 71:79 lower LDL 71:79 Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen. 34855475 1 1 theme cholesterol 147:157 arg1 levels 113:118 Increased blood levels 97:118 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen 97:180 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 1 1 theme cholesterol 147:157 arg1 factors 203:209 independent risk factors 186:209 independent risk factors for cardiovascular disease 186:236 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 3 2 dep disease 631:637 arg1 = 661:661 = 661:661 = 661:661 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 3 3 with association 588:598 arg1 disease 631:637 decreased coronary artery disease 605:637 decreased coronary artery disease (odds ratio = 0.64, P = 0.006) 605:668 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 3 4 theme = 651:651 arg1 ratio 645:649 odds ratio 640:649 odds ratio = 0.64 640:656 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 7 5 theme protein 1092:1098 arg1 galactosylation 1100:1114 protein galactosylation 1092:1114 protein galactosylation 1092:1114 Our findings suggest that targeted modulation of protein galactosylation may represent a therapeutic approach to decreasing cardiovascular disease. 34855475 2 6 theme beta-1,4-galactosyltransferase 349:378 arg1 domain 339:344 a functional domain 326:344 a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5) 326:527 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 6 theme beta-1,4-galactosyltransferase 349:378 arg1 milligrams 401:410 13.9 milligrams 396:410 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5) 396:527 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 6 theme beta-1,4-galactosyltransferase 349:378 arg1 beta-1,4-galactosyltransferase 349:378 beta-1,4-galactosyltransferase 1 349:380 beta-1,4-galactosyltransferase 1 (B4GALT1) 349:390 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 5 7 theme immunoglobulin 937:950 arg1 G 952:952 immunoglobulin G 937:952 immunoglobulin G 937:952 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 2 8 dep = 515:515 arg1 10–5 523:526 1.3 × 10–5 517:526 1.3 × 10–5 517:526 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 7 9 theme targeted 1069:1076 arg1 modulation 1078:1087 targeted modulation 1069:1087 targeted modulation of protein galactosylation 1069:1114 Our findings suggest that targeted modulation of protein galactosylation may represent a therapeutic approach to decreasing cardiovascular disease. 34855475 3 10 theme gene–based 538:547 arg1 analysis 549:556 B4GALT1 gene–based analysis 530:556 B4GALT1 gene–based analysis in 544,955 subjects 530:576 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 5 11 gly sialylation 889:899 arg1 fibrinogen 925:934 fibrinogen 925:934 fibrinogen 925:934 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 5 11 gly sialylation 889:899 arg1 G 952:952 immunoglobulin G 937:952 immunoglobulin G 937:952 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 5 11 gly sialylation 889:899 arg1 B100 919:922 apolipoprotein B100 904:922 apolipoprotein B100 904:922 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 5 11 gly sialylation 889:899 arg1 transferrin 959:969 transferrin 959:969 transferrin 959:969 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 0 12 from variant 49:55 arg1 B4GALT1 60:66 B4GALT1 60:66 B4GALT1 60:66 Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen. 34855475 5 13 theme fibrinogen 925:934 arg1 sialylation 889:899 sialylation 889:899 sialylation 889:899 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 5 13 theme fibrinogen 925:934 arg1 galactosylation 869:883 galactosylation 869:883 galactosylation 869:883 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 2 14 theme missense 292:299 arg1 p.Asn352Ser 310:320 p.Asn352Ser 310:320 p.Asn352Ser 310:320 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 14 theme missense 292:299 arg1 variant 301:307 an Amish-enriched missense variant 274:307 an Amish-enriched missense variant (p.Asn352Ser) 274:321 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 15 theme plasma 494:499 arg1 fibrinogen 501:510 plasma fibrinogen 494:510 deciliter lower plasma fibrinogen (P = 1.3 × 10–5) 478:527 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 16 theme lower 426:430 arg1 LDL-C 432:436 deciliter lower LDL-C 416:436 deciliter lower LDL-C (P = 4.1 × 10–19) 416:454 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 17 theme Amish-enriched 277:290 arg1 p.Asn352Ser 310:320 p.Asn352Ser 310:320 p.Asn352Ser 310:320 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 17 theme Amish-enriched 277:290 arg1 variant 301:307 an Amish-enriched missense variant 274:307 an Amish-enriched missense variant (p.Asn352Ser) 274:321 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 18 theme milligrams 401:410 arg1 domain 339:344 a functional domain 326:344 a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5) 326:527 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 18 theme milligrams 401:410 arg1 milligrams 401:410 13.9 milligrams 396:410 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5) 396:527 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 18 theme milligrams 401:410 arg1 beta-1,4-galactosyltransferase 349:378 beta-1,4-galactosyltransferase 1 349:380 beta-1,4-galactosyltransferase 1 (B4GALT1) 349:390 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 19 theme lower 488:492 arg1 fibrinogen 501:510 plasma fibrinogen 494:510 deciliter lower plasma fibrinogen (P = 1.3 × 10–5) 478:527 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 0 20 attach links 32:36 arg1 fibrinogen 85:94 fibrinogen 85:94 fibrinogen 85:94 Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen. 34855475 0 20 attach links 32:36 arg2 evidence 23:30 Genetic and functional evidence 0:30 Genetic and functional evidence 0:30 Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen. 34855475 0 20 attach links 32:36 arg1 LDL 77:79 lower LDL 71:79 lower LDL 71:79 Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen. 34855475 0 21 theme Genetic 0:6 arg1 evidence 23:30 Genetic and functional evidence 0:30 Genetic and functional evidence 0:30 Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen. 34855475 7 22 theme cardiovascular 1167:1180 arg1 disease 1182:1188 cardiovascular disease 1167:1188 cardiovascular disease 1167:1188 Our findings suggest that targeted modulation of protein galactosylation may represent a therapeutic approach to decreasing cardiovascular disease. 34855475 4 23 theme mutant 675:680 arg1 protein 682:688 The mutant protein 671:688 The mutant protein 671:688 The mutant protein had 50% lower galactosyltransferase activity compared with the wild-type protein. 34855475 5 24 theme serine 819:824 arg1 allele 830:835 serine 352 allele 819:835 serine 352 allele 819:835 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 2 25 theme = 441:441 arg1 P 439:439 P 439:439 P = 4.1 × 10–19 439:453 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 3 26 dep = 651:651 arg1 0.64 653:656 0.64 653:656 0.64 653:656 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 2 27 dep = 441:441 arg1 × 447:447 4.1 × 10–19 443:453 4.1 × 10–19 443:453 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 3 28 theme B4GALT1 530:536 arg1 analysis 549:556 B4GALT1 gene–based analysis 530:556 B4GALT1 gene–based analysis in 544,955 subjects 530:576 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 1 29 theme fibrinogen 171:180 arg1 levels 113:118 Increased blood levels 97:118 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen 97:180 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 1 29 theme fibrinogen 171:180 arg1 factors 203:209 independent risk factors 186:209 independent risk factors for cardiovascular disease 186:236 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 7 30 theme therapeutic 1132:1142 arg1 approach 1144:1151 a therapeutic approach 1130:1151 a therapeutic approach to decreasing cardiovascular disease 1130:1188 Our findings suggest that targeted modulation of protein galactosylation may represent a therapeutic approach to decreasing cardiovascular disease. 34855475 4 31 contain had 690:692 arg1 protein 682:688 The mutant protein 671:688 The mutant protein 671:688 The mutant protein had 50% lower galactosyltransferase activity compared with the wild-type protein. 34855475 4 31 contain had 690:692 arg2 activity 726:733 50% lower galactosyltransferase activity 694:733 50% lower galactosyltransferase activity 694:733 The mutant protein had 50% lower galactosyltransferase activity compared with the wild-type protein. 34855475 6 32 from decreases 1008:1016 arg1 fibrinogen 1031:1040 fibrinogen 1031:1040 fibrinogen 1031:1040 B4galt1 353Ser knock-in mice showed decreases in LDL-C and fibrinogen. 34855475 6 32 from decreases 1008:1016 arg1 LDL-C 1021:1025 LDL-C 1021:1025 LDL-C 1021:1025 B4galt1 353Ser knock-in mice showed decreases in LDL-C and fibrinogen. 34855475 5 33 theme apolipoprotein 904:917 arg1 B100 919:922 apolipoprotein B100 904:922 apolipoprotein B100 904:922 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 3 34 from analysis 549:556 arg1 subjects 569:576 544,955 subjects 561:576 544,955 subjects 561:576 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 5 35 theme glycan 781:786 arg1 profiling 788:796 N-linked glycan profiling 772:796 N-linked glycan profiling of human serum 772:811 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 0 36 theme functional 12:21 arg1 evidence 23:30 Genetic and functional evidence 0:30 Genetic and functional evidence 0:30 Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen. 34855475 4 37 theme galactosyltransferase 704:724 arg1 activity 726:733 50% lower galactosyltransferase activity 694:733 50% lower galactosyltransferase activity 694:733 The mutant protein had 50% lower galactosyltransferase activity compared with the wild-type protein. 34855475 3 38 theme coronary 615:622 arg1 disease 631:637 decreased coronary artery disease 605:637 decreased coronary artery disease (odds ratio = 0.64, P = 0.006) 605:668 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 5 39 theme B100 919:922 arg1 sialylation 889:899 sialylation 889:899 sialylation 889:899 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 5 39 theme B100 919:922 arg1 galactosylation 869:883 galactosylation 869:883 galactosylation 869:883 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 1 40 theme independent 186:196 arg1 levels 113:118 Increased blood levels 97:118 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen 97:180 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 1 40 theme independent 186:196 arg1 factors 203:209 independent risk factors 186:209 independent risk factors for cardiovascular disease 186:236 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 5 41 theme decreased 859:867 arg1 galactosylation 869:883 galactosylation 869:883 galactosylation 869:883 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 2 42 theme = 515:515 arg1 P 513:513 P 513:513 P = 1.3 × 10–5 513:526 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 3 43 theme artery 624:629 arg1 disease 631:637 decreased coronary artery disease 605:637 decreased coronary artery disease (odds ratio = 0.64, P = 0.006) 605:668 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 1 44 theme risk 198:201 arg1 levels 113:118 Increased blood levels 97:118 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen 97:180 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 1 44 theme risk 198:201 arg1 factors 203:209 independent risk factors 186:209 independent risk factors for cardiovascular disease 186:236 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 5 45 theme serum 807:811 arg1 profiling 788:796 N-linked glycan profiling 772:796 N-linked glycan profiling of human serum 772:811 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 3 46 dep = 661:661 arg1 ratio 645:649 odds ratio 640:649 odds ratio = 0.64 640:656 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 2 47 dep fibrinogen 501:510 arg1 P 513:513 P 513:513 P = 1.3 × 10–5 513:526 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 4 48 theme wild-type 753:761 arg1 protein 763:769 the wild-type protein 749:769 the wild-type protein 749:769 The mutant protein had 50% lower galactosyltransferase activity compared with the wild-type protein. 34855475 5 49 theme human 801:805 arg1 serum 807:811 human serum 801:811 human serum 801:811 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 7 50 theme galactosylation 1100:1114 arg1 modulation 1078:1087 targeted modulation 1069:1087 targeted modulation of protein galactosylation 1069:1114 Our findings suggest that targeted modulation of protein galactosylation may represent a therapeutic approach to decreasing cardiovascular disease. 34855475 5 51 theme N-linked 772:779 arg1 profiling 788:796 N-linked glycan profiling 772:796 N-linked glycan profiling of human serum 772:811 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 3 52 theme decreased 605:613 arg1 disease 631:637 decreased coronary artery disease 605:637 decreased coronary artery disease (odds ratio = 0.64, P = 0.006) 605:668 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 2 53 dep LDL-C 432:436 arg1 P 439:439 P 439:439 P = 4.1 × 10–19 439:453 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 1 54 theme Increased 97:105 arg1 levels 113:118 Increased blood levels 97:118 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen 97:180 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 1 54 theme Increased 97:105 arg1 factors 203:209 independent risk factors 186:209 independent risk factors for cardiovascular disease 186:236 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 0 55 theme missense 40:47 arg1 variant 49:55 a missense variant 38:55 a missense variant in B4GALT1 38:66 Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen. 34855475 3 56 theme odds 640:643 arg1 ratio 645:649 odds ratio 640:649 odds ratio = 0.64 640:656 B4GALT1 gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). 34855475 1 57 theme blood 107:111 arg1 levels 113:118 Increased blood levels 97:118 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen 97:180 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 1 57 theme blood 107:111 arg1 factors 203:209 independent risk factors 186:209 independent risk factors for cardiovascular disease 186:236 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 5 58 theme G 952:952 arg1 sialylation 889:899 sialylation 889:899 sialylation 889:899 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 5 58 theme G 952:952 arg1 galactosylation 869:883 galactosylation 869:883 galactosylation 869:883 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 6 59 theme 353Ser 980:985 arg1 mice 996:999 B4galt1 353Ser knock-in mice 972:999 B4galt1 353Ser knock-in mice 972:999 B4galt1 353Ser knock-in mice showed decreases in LDL-C and fibrinogen. 34855475 2 60 theme functional 328:337 arg1 domain 339:344 a functional domain 326:344 a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5) 326:527 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 60 theme functional 328:337 arg1 milligrams 401:410 13.9 milligrams 396:410 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5) 396:527 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 2 60 theme functional 328:337 arg1 beta-1,4-galactosyltransferase 349:378 beta-1,4-galactosyltransferase 1 349:380 beta-1,4-galactosyltransferase 1 (B4GALT1) 349:390 We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 10–5). 34855475 6 61 theme knock-in 987:994 arg1 mice 996:999 B4galt1 353Ser knock-in mice 972:999 B4galt1 353Ser knock-in mice 972:999 B4galt1 353Ser knock-in mice showed decreases in LDL-C and fibrinogen. 34855475 4 62 theme lower 698:702 arg1 activity 726:733 50% lower galactosyltransferase activity 694:733 50% lower galactosyltransferase activity 694:733 The mutant protein had 50% lower galactosyltransferase activity compared with the wild-type protein. 34855475 5 63 link N-linked 772:779 arg1 profiling 788:796 N-linked glycan profiling 772:796 N-linked glycan profiling of human serum 772:811 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 1 64 theme cardiovascular 215:228 arg1 disease 230:236 cardiovascular disease 215:236 cardiovascular disease 215:236 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 1 65 theme low-density 123:133 arg1 LDL-C 160:164 LDL-C 160:164 LDL-C 160:164 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 1 65 theme low-density 123:133 arg1 cholesterol 147:157 low-density lipoprotein cholesterol 123:157 low-density lipoprotein cholesterol (LDL-C) 123:165 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 6 66 theme B4galt1 972:978 arg1 mice 996:999 B4galt1 353Ser knock-in mice 972:999 B4galt1 353Ser knock-in mice 972:999 B4galt1 353Ser knock-in mice showed decreases in LDL-C and fibrinogen. 34855475 5 67 theme transferrin 959:969 arg1 sialylation 889:899 sialylation 889:899 sialylation 889:899 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 5 67 theme transferrin 959:969 arg1 galactosylation 869:883 galactosylation 869:883 galactosylation 869:883 N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. 34855475 1 68 theme lipoprotein 135:145 arg1 LDL-C 160:164 LDL-C 160:164 LDL-C 160:164 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 34855475 1 68 theme lipoprotein 135:145 arg1 cholesterol 147:157 low-density lipoprotein cholesterol 123:157 low-density lipoprotein cholesterol (LDL-C) 123:165 Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. 33771926 6 0 theme glycosylation 1026:1038 arg1 sites 1040:1044 N-linked glycosylation sites 1017:1044 N-linked glycosylation sites 1017:1044 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 10 1 theme specific 1657:1664 arg1 mechanisms 1666:1675 specific mechanisms 1657:1675 specific mechanisms 1657:1675 Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome. 33771926 9 2 theme CD4 1373:1375 arg1 protein 1377:1383 the primate CD4 protein 1361:1383 the primate CD4 protein 1361:1383 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 5 3 theme SIV 827:829 arg1 entry 849:853 SIV Env-mediated cell entry 827:853 SIV Env-mediated cell entry 827:853 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 4 4 theme protein 606:612 arg1 protein 606:612 the CD4 protein 598:612 the CD4 protein 598:612 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 4 4 theme protein 606:612 arg1 domain 588:593 the outermost (D1) domain 569:593 the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes 569:641 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 1 5 gly glycoprotein 202:213 arg1 Env 216:218 Env 216:218 Env 216:218 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 1 5 gly glycoprotein 202:213 arg1 glycoprotein 202:213 the viral envelope glycoprotein 183:213 the viral envelope glycoprotein (Env) 183:219 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 10 6 theme disease 1686:1692 arg1 progression 1694:1704 disease progression 1686:1704 disease progression 1686:1704 Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome. 33771926 4 7 theme single 768:773 arg1 species 775:781 a single species 766:781 a single species 766:781 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 3 8 theme African 529:535 arg1 species 545:551 many African primate species 524:551 many African primate species 524:551 Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. 33771926 1 9 theme envelope 193:200 arg1 Env 216:218 Env 216:218 Env 216:218 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 1 9 theme envelope 193:200 arg1 glycoprotein 202:213 the viral envelope glycoprotein 183:213 the viral envelope glycoprotein (Env) 183:219 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 1 10 with Infection 96:104 arg1 viruses 145:151 human and simian immunodeficiency viruses 111:151 human and simian immunodeficiency viruses (HIV/SIV) 111:161 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 1 10 with Infection 96:104 arg1 HIV/SIV 154:160 HIV/SIV 154:160 HIV/SIV 154:160 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 4 11 from domain 588:593 arg1 apes 638:641 apes 638:641 apes 638:641 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 4 11 from domain 588:593 arg1 monkeys 626:632 over 500 monkeys 617:632 over 500 monkeys 617:632 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 1 12 theme immunodeficiency 128:143 arg1 viruses 145:151 human and simian immunodeficiency viruses 111:151 human and simian immunodeficiency viruses (HIV/SIV) 111:161 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 1 12 theme immunodeficiency 128:143 arg1 HIV/SIV 154:160 HIV/SIV 154:160 HIV/SIV 154:160 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 8 13 theme multiple 1213:1220 arg1 variants 1241:1248 multiple distinct D1 domain variants 1213:1248 multiple distinct D1 domain variants 1213:1248 shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. 33771926 8 14 theme D1 1231:1232 arg1 variants 1241:1248 multiple distinct D1 domain variants 1213:1248 multiple distinct D1 domain variants 1213:1248 shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. 33771926 5 15 theme Env-mediated 831:842 arg1 entry 849:853 SIV Env-mediated cell entry 827:853 SIV Env-mediated cell entry 827:853 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 4 16 theme polymorphic 653:663 arg1 residues 665:672 polymorphic residues 653:672 polymorphic residues in 24 of 29 primate species 653:700 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 5 17 theme single-round 860:871 arg1 assay 883:887 a single-round infection assay 858:887 a single-round infection assay 858:887 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 6 18 located found 1052:1056 arg1 species 1069:1075 primate species 1061:1075 primate species from different genera 1061:1097 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 6 18 located found 1052:1056 arg2 addition 1005:1012 the addition 1001:1012 the addition of N-linked glycosylation sites 1001:1044 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 6 18 located found 1052:1056 arg2 polymorphisms 976:988 Several identical CD4 polymorphisms 954:988 Several identical CD4 polymorphisms 954:988 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 6 19 theme parallel 1131:1138 arg1 evolution 1140:1148 parallel evolution 1131:1148 parallel evolution 1131:1148 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 10 20 theme long-term 1613:1621 arg1 species 1636:1642 long-term SIV-infected species 1613:1642 long-term SIV-infected species 1613:1642 Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome. 33771926 7 21 theme different 1167:1175 arg1 guenons 1177:1183 seven different guenons 1161:1183 seven different guenons (Cercopithecus spp.) 1161:1204 Moreover, seven different guenons (Cercopithecus spp.) 33771926 5 22 theme acid 800:803 arg1 replacements 805:816 D1 domain amino acid replacements 784:816 D1 domain amino acid replacements 784:816 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 2 23 from invariant 286:294 arg1 humans 299:304 humans 299:304 humans 299:304 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 8 24 theme long-term 1263:1271 arg1 polymorphism 1288:1299 long-term trans-specific polymorphism 1263:1299 long-term trans-specific polymorphism 1263:1299 shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. 33771926 2 25 from humans 299:304 arg1 invariant 286:294 invariant 286:294 invariant 286:294 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 4 26 theme primate 686:692 arg1 species 694:700 24 of 29 primate species 677:700 24 of 29 primate species 677:700 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 2 27 theme wild 416:419 arg1 populations 421:431 wild populations 416:431 wild populations 416:431 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 0 28 theme CD4 0:2 arg1 diversity 13:21 CD4 receptor diversity 0:21 CD4 receptor diversity 0:21 CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses. 33771926 2 29 theme coding 385:390 arg1 variants 392:399 nine coding variants 380:399 nine coding variants circulating in wild populations 380:431 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 1 30 theme cells 270:274 arg1 surface 252:258 the surface 248:258 the surface of immune cells 248:274 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 5 31 theme infection 873:881 arg1 assay 883:887 a single-round infection assay 858:887 a single-round infection assay 858:887 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 4 32 theme different 722:730 arg1 variants 739:746 as many as 11 different coding variants 708:746 as many as 11 different coding variants identified within a single species 708:781 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 9 33 theme years 1529:1533 arg1 millions 1517:1524 millions 1517:1524 millions of years 1517:1533 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 6 34 theme identical 962:970 arg1 polymorphisms 976:988 Several identical CD4 polymorphisms 954:988 Several identical CD4 polymorphisms 954:988 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 6 34 theme identical 962:970 arg1 addition 1005:1012 the addition 1001:1012 the addition of N-linked glycosylation sites 1001:1044 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 2 35 theme binding 315:321 arg1 CD4 348:350 the chimpanzee CD4 333:350 the chimpanzee CD4 333:350 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 2 35 theme binding 315:321 arg1 polymorphic 362:372 polymorphic 362:372 polymorphic 362:372 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 2 35 theme binding 315:321 arg1 domain 323:328 the Env binding domain 307:328 the Env binding domain of the chimpanzee CD4 307:350 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 0 36 theme protection 45:54 arg1 mechanism 56:64 an ancient protection mechanism 34:64 an ancient protection mechanism against primate lentiviruses 34:93 CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses. 33771926 6 37 link N-linked 1017:1024 arg1 sites 1040:1044 N-linked glycosylation sites 1017:1044 N-linked glycosylation sites 1017:1044 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 9 38 theme HIV/SIV 1331:1337 arg1 variable 1395:1402 variable 1395:1402 variable 1395:1402 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 9 38 theme HIV/SIV 1331:1337 arg1 region 1351:1356 the HIV/SIV Env binding region 1327:1356 the HIV/SIV Env binding region of the primate CD4 protein 1327:1383 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 2 39 theme chimpanzee 337:346 arg1 CD4 348:350 the chimpanzee CD4 333:350 the chimpanzee CD4 333:350 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 9 40 theme binding 1343:1349 arg1 variable 1395:1402 variable 1395:1402 variable 1395:1402 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 9 40 theme binding 1343:1349 arg1 region 1351:1356 the HIV/SIV Env binding region 1327:1356 the HIV/SIV Env binding region of the primate CD4 protein 1327:1383 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 6 41 theme sites 1040:1044 arg1 addition 1005:1012 the addition 1001:1012 the addition of N-linked glycosylation sites 1001:1044 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 3 42 theme CD4 468:470 arg1 diversity 472:480 within-species CD4 diversity 453:480 within-species CD4 diversity 453:480 Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. 33771926 2 43 with polymorphic 362:372 arg1 variants 392:399 nine coding variants 380:399 nine coding variants circulating in wild populations 380:431 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 6 44 theme N-linked 1017:1024 arg1 sites 1040:1044 N-linked glycosylation sites 1017:1044 N-linked glycosylation sites 1017:1044 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 10 45 theme primate 1707:1713 arg1 lentiviruses 1715:1726 primate lentiviruses 1707:1726 primate lentiviruses 1707:1726 Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome. 33771926 9 46 theme primate 1365:1371 arg1 protein 1377:1383 the primate CD4 protein 1361:1383 the primate CD4 protein 1361:1383 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 9 47 theme primate 1582:1588 arg1 lentiviruses 1590:1601 primate lentiviruses 1582:1601 primate lentiviruses 1582:1601 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 6 48 theme striking 1110:1117 arg1 examples 1119:1126 striking examples 1110:1126 striking examples of parallel evolution 1110:1148 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 1 49 theme viral 187:191 arg1 Env 216:218 Env 216:218 Env 216:218 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 1 49 theme viral 187:191 arg1 glycoprotein 202:213 the viral envelope glycoprotein 183:213 the viral envelope glycoprotein (Env) 183:219 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 9 50 theme protein 1377:1383 arg1 variable 1395:1402 variable 1395:1402 variable 1395:1402 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 9 50 theme protein 1377:1383 arg1 region 1351:1356 the HIV/SIV Env binding region 1327:1356 the HIV/SIV Env binding region of the primate CD4 protein 1327:1383 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 4 51 theme CD4 602:604 arg1 protein 606:612 the CD4 protein 598:612 the CD4 protein 598:612 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 3 52 theme many 524:527 arg1 species 545:551 many African primate species 524:551 many African primate species 524:551 Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. 33771926 5 53 theme D1 784:785 arg1 replacements 805:816 D1 domain amino acid replacements 784:816 D1 domain amino acid replacements 784:816 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 6 54 theme different 1082:1090 arg1 genera 1092:1097 different genera 1082:1097 different genera 1082:1097 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 1 55 theme glycoprotein 202:213 arg1 binding 172:178 binding 172:178 binding of the viral envelope glycoprotein (Env) to the host protein CD4 172:243 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 2 56 theme Env 311:313 arg1 CD4 348:350 the chimpanzee CD4 333:350 the chimpanzee CD4 333:350 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 2 56 theme Env 311:313 arg1 polymorphic 362:372 polymorphic 362:372 polymorphic 362:372 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 2 56 theme Env 311:313 arg1 domain 323:328 the Env binding domain 307:328 the Env binding domain of the chimpanzee CD4 307:350 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 5 57 theme domain 787:792 arg1 replacements 805:816 D1 domain amino acid replacements 784:816 D1 domain amino acid replacements 784:816 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 10 58 dep left 1766:1769 arg1 mark 1777:1780 mark 1777:1780 mark 1777:1780 Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome. 33771926 3 59 theme primate 537:543 arg1 species 545:551 many African primate species 524:551 many African primate species 524:551 Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. 33771926 1 60 theme simian 121:126 arg1 viruses 145:151 human and simian immunodeficiency viruses 111:151 human and simian immunodeficiency viruses (HIV/SIV) 111:161 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 1 60 theme simian 121:126 arg1 HIV/SIV 154:160 HIV/SIV 154:160 HIV/SIV 154:160 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 8 61 theme distinct 1222:1229 arg1 variants 1241:1248 multiple distinct D1 domain variants 1213:1248 multiple distinct D1 domain variants 1213:1248 shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. 33771926 10 62 theme host 1789:1792 arg1 genome 1794:1799 the host genome 1785:1799 the host genome 1785:1799 Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome. 33771926 5 63 theme cell 844:847 arg1 entry 849:853 SIV Env-mediated cell entry 827:853 SIV Env-mediated cell entry 827:853 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 6 64 theme Several 954:960 arg1 polymorphisms 976:988 Several identical CD4 polymorphisms 954:988 Several identical CD4 polymorphisms 954:988 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 6 64 theme Several 954:960 arg1 addition 1005:1012 the addition 1001:1012 the addition of N-linked glycosylation sites 1001:1044 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 6 65 theme evolution 1140:1148 arg1 examples 1119:1126 striking examples 1110:1126 striking examples of parallel evolution 1110:1148 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 8 66 theme domain 1234:1239 arg1 variants 1241:1248 multiple distinct D1 domain variants 1213:1248 multiple distinct D1 domain variants 1213:1248 shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. 33771926 0 67 theme primate 74:80 arg1 lentiviruses 82:93 primate lentiviruses 74:93 primate lentiviruses 74:93 CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses. 33771926 5 68 theme amino 794:798 arg1 replacements 805:816 D1 domain amino acid replacements 784:816 D1 domain amino acid replacements 784:816 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 6 69 gly glycosylation 1026:1038 arg2 sites 1040:1044 N-linked glycosylation sites 1017:1044 N-linked glycosylation sites 1017:1044 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 8 70 theme trans-specific 1273:1286 arg1 polymorphism 1288:1299 long-term trans-specific polymorphism 1263:1299 long-term trans-specific polymorphism 1263:1299 shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. 33771926 0 71 theme receptor 4:11 arg1 diversity 13:21 CD4 receptor diversity 0:21 CD4 receptor diversity 0:21 CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses. 33771926 7 72 dep guenons 1177:1183 arg1 spp 1200:1202 Cercopithecus spp 1186:1202 Cercopithecus spp. 1186:1203 Moreover, seven different guenons (Cercopithecus spp.) 33771926 10 73 contain have 1761:1764 arg1 lentiviruses 1715:1726 primate lentiviruses 1707:1726 primate lentiviruses 1707:1726 Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome. 33771926 10 73 contain have 1761:1764 arg2 left 1766:1769 left 1766:1769 left 1766:1769 Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome. 33771926 2 74 theme CD4 348:350 arg1 CD4 348:350 the chimpanzee CD4 333:350 the chimpanzee CD4 333:350 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 2 74 theme CD4 348:350 arg1 polymorphic 362:372 polymorphic 362:372 polymorphic 362:372 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 2 74 theme CD4 348:350 arg1 domain 323:328 the Env binding domain 307:328 the Env binding domain of the chimpanzee CD4 307:350 Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. 33771926 1 75 theme immune 263:268 arg1 cells 270:274 immune cells 263:274 immune cells 263:274 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 4 76 from residues 665:672 arg1 species 694:700 24 of 29 primate species 677:700 24 of 29 primate species 677:700 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 1 77 theme human 111:115 arg1 viruses 145:151 human and simian immunodeficiency viruses 111:151 human and simian immunodeficiency viruses (HIV/SIV) 111:161 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 1 77 theme human 111:115 arg1 HIV/SIV 154:160 HIV/SIV 154:160 HIV/SIV 154:160 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 6 78 from genera 1092:1097 arg1 species 1069:1075 primate species 1061:1075 primate species from different genera 1061:1097 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 0 79 theme ancient 37:43 arg1 mechanism 56:64 an ancient protection mechanism 34:64 an ancient protection mechanism against primate lentiviruses 34:93 CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses. 33771926 5 80 theme allele-specific 929:943 arg1 fashion 945:951 a strain- and allele-specific fashion 915:951 a strain- and allele-specific fashion 915:951 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 6 81 theme CD4 972:974 arg1 polymorphisms 976:988 Several identical CD4 polymorphisms 954:988 Several identical CD4 polymorphisms 954:988 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 6 81 theme CD4 972:974 arg1 addition 1005:1012 the addition 1001:1012 the addition of N-linked glycosylation sites 1001:1044 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 1 82 theme host 228:231 arg1 CD4 241:243 the host protein CD4 224:243 the host protein CD4 224:243 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 33771926 6 83 theme primate 1061:1067 arg1 species 1069:1075 primate species 1061:1075 primate species from different genera 1061:1097 Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. 33771926 4 84 theme coding 732:737 arg1 variants 739:746 as many as 11 different coding variants 708:746 as many as 11 different coding variants identified within a single species 708:781 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 3 85 theme within-species 453:466 arg1 diversity 472:480 within-species CD4 diversity 453:480 within-species CD4 diversity 453:480 Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. 33771926 4 86 theme outermost 573:581 arg1 protein 606:612 the CD4 protein 598:612 the CD4 protein 598:612 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 4 86 theme outermost 573:581 arg1 domain 588:593 the outermost (D1) domain 569:593 the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes 569:641 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 10 87 theme SIV-infected 1623:1634 arg1 species 1636:1642 long-term SIV-infected species 1613:1642 long-term SIV-infected species 1613:1642 Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome. 33771926 9 88 theme Env 1339:1341 arg1 variable 1395:1402 variable 1395:1402 variable 1395:1402 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 9 88 theme Env 1339:1341 arg1 region 1351:1356 the HIV/SIV Env binding region 1327:1356 the HIV/SIV Env binding region of the primate CD4 protein 1327:1383 These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. 33771926 5 89 theme strain- 917:923 arg1 fashion 945:951 a strain- and allele-specific fashion 915:951 a strain- and allele-specific fashion 915:951 D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. 33771926 7 90 theme Cercopithecus 1186:1198 arg1 spp 1200:1202 Cercopithecus spp 1186:1202 Cercopithecus spp. 1186:1203 Moreover, seven different guenons (Cercopithecus spp.) 33771926 4 91 theme D1 584:585 arg1 protein 606:612 the CD4 protein 598:612 the CD4 protein 598:612 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 4 91 theme D1 584:585 arg1 domain 588:593 the outermost (D1) domain 569:593 the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes 569:641 Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. 33771926 1 92 theme protein 233:239 arg1 CD4 241:243 the host protein CD4 224:243 the host protein CD4 224:243 Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. 35737812 7 0 from analyses 976:983 arg1 cohorts 1011:1017 early pandemic patient cohorts 988:1017 early pandemic patient cohorts 988:1017 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 2 1 theme precise 139:145 arg1 analyses 147:154 precise analyses 139:154 precise analyses of glycan ligands binding with heavily modified pathogen proteins 139:220 However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. 35737812 5 2 theme microscopy 736:745 arg1 structure 747:755 a high-resolution cryo-electron microscopy structure 704:755 a high-resolution cryo-electron microscopy structure 704:755 uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. 35737812 7 3 theme tetraantennary 1088:1101 arg1 glycoproteins 1112:1124 tetraantennary N-linked glycoproteins 1088:1124 tetraantennary N-linked glycoproteins deep in the human lung 1088:1147 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 7 4 theme early 988:992 arg1 cohorts 1011:1017 early pandemic patient cohorts 988:1017 early pandemic patient cohorts 988:1017 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 4 5 theme syndrome 584:591 arg1 coronavirus 593:603 B-origin-lineage severe acute respiratory syndrome coronavirus 2 542:605 B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 542:618 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 4 5 theme syndrome 584:591 arg1 SARS-CoV-2 608:617 SARS-CoV-2 608:617 SARS-CoV-2 608:617 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 7 6 theme variance 967:974 arg1 analyses 976:983 genetic variance analyses 959:983 genetic variance analyses in early pandemic patient cohorts 959:1017 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 4 7 dep early-pandemic 526:539 arg1 spike 620:624 spike 620:624 spike 620:624 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 3 8 theme magnetic 397:404 arg1 resonance 406:414 nuclear magnetic resonance 389:414 nuclear magnetic resonance spectroscopy 389:427 Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. 35737812 6 9 theme sugar 896:900 arg1 binding 902:908 sugar binding 896:908 sugar binding in SARS-CoV-2 variants of concern 896:942 This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. 35737812 4 10 theme " 669:669 arg1 manner 671:676 an "end-on" manner 659:676 an "end-on" manner 659:676 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 3 11 theme resonance 406:414 arg1 spectroscopy 416:427 nuclear magnetic resonance spectroscopy 389:427 nuclear magnetic resonance spectroscopy 389:427 Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. 35737812 4 12 theme severe 559:564 arg1 coronavirus 593:603 B-origin-lineage severe acute respiratory syndrome coronavirus 2 542:605 B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 542:618 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 4 12 theme severe 559:564 arg1 SARS-CoV-2 608:617 SARS-CoV-2 608:617 SARS-CoV-2 608:617 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 7 13 theme human 1138:1142 arg1 lung 1144:1147 the human lung 1134:1147 the human lung 1134:1147 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 5 14 theme uSTA-guided 679:689 arg1 modeling 691:698 uSTA-guided modeling 679:698 uSTA-guided modeling 679:698 uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. 35737812 1 15 theme Many 80:83 arg1 pathogens 85:93 Many pathogens 80:93 Many pathogens 80:93 Many pathogens exploit host cell-surface glycans. 35737812 4 16 theme end-on 663:668 arg1 manner 671:676 an "end-on" manner 659:676 an "end-on" manner 659:676 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 2 17 theme ligands 166:172 arg1 analyses 147:154 precise analyses 139:154 precise analyses of glycan ligands binding with heavily modified pathogen proteins 139:220 However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. 35737812 7 18 theme polylactosamine 1057:1071 arg1 motif 1073:1077 a sialylated polylactosamine motif 1044:1077 a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung 1044:1147 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 7 19 theme genetic 959:965 arg1 analyses 976:983 genetic variance analyses 959:983 genetic variance analyses in early pandemic patient cohorts 959:1017 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 3 20 theme nuclear 389:395 arg1 resonance 406:414 nuclear magnetic resonance 389:414 nuclear magnetic resonance spectroscopy 389:427 Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. 35737812 2 21 theme glycan 159:164 arg1 ligands 166:172 glycan ligands 159:172 glycan ligands binding with heavily modified pathogen proteins 159:220 However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. 35737812 7 22 located found 1079:1083 arg1 glycoproteins 1112:1124 tetraantennary N-linked glycoproteins 1088:1124 tetraantennary N-linked glycoproteins deep in the human lung 1088:1147 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 7 22 located found 1079:1083 arg2 motif 1073:1077 a sialylated polylactosamine motif 1044:1077 a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung 1044:1147 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 2 23 theme experimental 298:309 arg1 constraints 311:321 known experimental constraints 292:321 known experimental constraints 292:321 However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. 35737812 7 24 theme sialylated 1046:1055 arg1 motif 1073:1077 a sialylated polylactosamine motif 1044:1077 a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung 1044:1147 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 4 25 theme acute 566:570 arg1 coronavirus 593:603 B-origin-lineage severe acute respiratory syndrome coronavirus 2 542:605 B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 542:618 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 4 25 theme acute 566:570 arg1 SARS-CoV-2 608:617 SARS-CoV-2 608:617 SARS-CoV-2 608:617 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 5 26 theme high-resolution 706:720 arg1 microscopy 736:745 a high-resolution cryo-electron microscopy 704:745 a high-resolution cryo-electron microscopy structure 704:755 uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. 35737812 6 27 theme mutations 873:881 arg1 effect 859:864 the effect 855:864 the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern 855:942 This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. 35737812 1 28 theme host 103:106 arg1 glycans 121:127 host cell-surface glycans 103:127 host cell-surface glycans 103:127 Many pathogens exploit host cell-surface glycans. 35737812 4 29 theme B-origin-lineage 542:557 arg1 coronavirus 593:603 B-origin-lineage severe acute respiratory syndrome coronavirus 2 542:605 B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 542:618 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 4 29 theme B-origin-lineage 542:557 arg1 SARS-CoV-2 608:617 SARS-CoV-2 608:617 SARS-CoV-2 608:617 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 3 30 theme protein-ligand 479:492 arg1 interactions 494:505 protein-ligand interactions 479:505 protein-ligand interactions 479:505 Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. 35737812 0 31 theme Pathogen-sugar 0:13 arg1 interactions 15:26 Pathogen-sugar interactions 0:26 Pathogen-sugar interactions 0:26 Pathogen-sugar interactions revealed by universal saturation transfer analysis. 35737812 4 32 theme sialoside 639:647 arg1 sugars 649:654 sialoside sugars 639:654 sialoside sugars 639:654 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 5 33 theme cryo-electron 722:734 arg1 microscopy 736:745 a high-resolution cryo-electron microscopy 704:745 a high-resolution cryo-electron microscopy structure 704:755 uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. 35737812 6 34 theme NTD 869:871 arg1 mutations 873:881 NTD mutations 869:881 NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern 869:942 This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. 35737812 1 35 theme cell-surface 108:119 arg1 glycans 121:127 host cell-surface glycans 103:127 host cell-surface glycans 103:127 Many pathogens exploit host cell-surface glycans. 35737812 6 36 from binding 902:908 arg1 variants 924:931 SARS-CoV-2 variants 913:931 SARS-CoV-2 variants of concern 913:942 This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. 35737812 7 37 gly sialylated 1046:1055 arg1 motif 1073:1077 a sialylated polylactosamine motif 1044:1077 a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung 1044:1147 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 7 38 link N-linked 1103:1110 arg1 glycoproteins 1112:1124 tetraantennary N-linked glycoproteins 1088:1124 tetraantennary N-linked glycoproteins deep in the human lung 1088:1147 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 3 39 theme Universal 324:332 arg1 transfer 345:352 Universal saturation transfer 324:352 Universal saturation transfer analysis (uSTA) 324:368 Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. 35737812 2 40 theme pathogen 204:211 arg1 proteins 213:220 heavily modified pathogen proteins 187:220 heavily modified pathogen proteins 187:220 However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. 35737812 0 41 theme saturation 50:59 arg1 analysis 70:77 universal saturation transfer analysis 40:77 universal saturation transfer analysis 40:77 Pathogen-sugar interactions revealed by universal saturation transfer analysis. 35737812 2 42 theme modified 195:202 arg1 proteins 213:220 heavily modified pathogen proteins 187:220 heavily modified pathogen proteins 187:220 However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. 35737812 0 43 theme universal 40:48 arg1 analysis 70:77 universal saturation transfer analysis 40:77 universal saturation transfer analysis 40:77 Pathogen-sugar interactions revealed by universal saturation transfer analysis. 35737812 2 44 theme sugar 255:259 arg1 signals 261:267 overlapping sugar signals 243:267 overlapping sugar signals 243:267 However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. 35737812 3 45 theme automated 443:451 arg1 workflow 453:460 an automated workflow 440:460 an automated workflow for quantitating protein-ligand interactions 440:505 Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. 35737812 5 46 theme end-on 813:818 arg1 binding 820:826 end-on binding 813:826 end-on binding 813:826 uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. 35737812 5 47 theme spike 771:775 arg1 domain 788:793 the spike N-terminal domain 767:793 the spike N-terminal domain (NTD) 767:799 uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. 35737812 5 47 theme spike 771:775 arg1 NTD 796:798 NTD 796:798 NTD 796:798 uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. 35737812 4 48 theme early-pandemic 526:539 arg1 trimer 626:631 early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer 526:631 early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer 526:631 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 2 49 theme overlapping 243:253 arg1 signals 261:267 overlapping sugar signals 243:267 overlapping sugar signals 243:267 However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. 35737812 4 50 theme respiratory 572:582 arg1 coronavirus 593:603 B-origin-lineage severe acute respiratory syndrome coronavirus 2 542:605 B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 542:618 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 4 50 theme respiratory 572:582 arg1 SARS-CoV-2 608:617 SARS-CoV-2 608:617 SARS-CoV-2 608:617 uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. 35737812 0 51 theme transfer 61:68 arg1 analysis 70:77 universal saturation transfer analysis 40:77 universal saturation transfer analysis 40:77 Pathogen-sugar interactions revealed by universal saturation transfer analysis. 35737812 5 52 theme N-terminal 777:786 arg1 domain 788:793 the spike N-terminal domain 767:793 the spike N-terminal domain (NTD) 767:799 uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. 35737812 5 52 theme N-terminal 777:786 arg1 NTD 796:798 NTD 796:798 NTD 796:798 uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. 35737812 6 53 theme concern 936:942 arg1 variants 924:931 SARS-CoV-2 variants 913:931 SARS-CoV-2 variants of concern 913:942 This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. 35737812 3 54 theme saturation 334:343 arg1 transfer 345:352 Universal saturation transfer 324:352 Universal saturation transfer analysis (uSTA) 324:368 Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. 35737812 2 55 theme known 292:296 arg1 constraints 311:321 known experimental constraints 292:321 known experimental constraints 292:321 However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. 35737812 3 56 theme transfer 345:352 arg1 uSTA 364:367 uSTA 364:367 uSTA 364:367 Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. 35737812 3 56 theme transfer 345:352 arg1 analysis 354:361 Universal saturation transfer analysis 324:361 Universal saturation transfer analysis (uSTA) 324:368 Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. 35737812 7 57 theme N-linked 1103:1110 arg1 glycoproteins 1112:1124 tetraantennary N-linked glycoproteins 1088:1124 tetraantennary N-linked glycoproteins deep in the human lung 1088:1147 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 7 58 theme pandemic 994:1001 arg1 cohorts 1011:1017 early pandemic patient cohorts 988:1017 early pandemic patient cohorts 988:1017 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 6 59 theme SARS-CoV-2 913:922 arg1 variants 924:931 SARS-CoV-2 variants 913:931 SARS-CoV-2 variants of concern 913:942 This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. 35737812 7 60 gly glycoproteins 1112:1124 arg1 glycoproteins 1112:1124 tetraantennary N-linked glycoproteins 1088:1124 tetraantennary N-linked glycoproteins deep in the human lung 1088:1147 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 35737812 7 61 theme patient 1003:1009 arg1 cohorts 1011:1017 early pandemic patient cohorts 988:1017 early pandemic patient cohorts 988:1017 Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. 1502687 6 0 theme molecular 736:744 arg1 oligosaccharides 760:775 high molecular weight sialyl oligosaccharides 731:775 high molecular weight sialyl oligosaccharides with repeating structures 731:801 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 4 1 theme sialyl 591:596 arg1 oligosaccharides 598:613 sialyl oligosaccharides 591:613 sialyl oligosaccharides 591:613 The oligosaccharides in the urine and the ascites were composed almost entirely of sialyl oligosaccharides. 1502687 4 2 from oligosaccharides 512:527 arg1 urine 536:540 the urine 532:540 the urine 532:540 The oligosaccharides in the urine and the ascites were composed almost entirely of sialyl oligosaccharides. 1502687 4 2 from oligosaccharides 512:527 arg1 ascites 550:556 the ascites 546:556 the ascites 546:556 The oligosaccharides in the urine and the ascites were composed almost entirely of sialyl oligosaccharides. 1502687 0 3 theme abdominal 101:109 arg1 ascites 111:117 the abdominal ascites 97:117 the abdominal ascites 97:117 Severe infantile sialidosis--the characteristics of oligosaccharides isolated from the urine and the abdominal ascites. 1502687 3 4 dep excreted 420:427 arg1 oligosaccharides 403:418 urinary oligosaccharides 395:418 urinary oligosaccharides excreted (nmol/mg creatinine) 395:448 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. 1502687 3 4 dep excreted 420:427 arg1 creatinine 438:447 nmol/mg creatinine 430:447 nmol/mg creatinine 430:447 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. 1502687 2 5 theme abdominal 296:304 arg1 ascites 306:312 the abdominal ascites 292:312 the abdominal ascites of this patient 292:328 Oligosaccharides in the urine and the abdominal ascites of this patient were investigated by Bio-Gel column chromatography. 1502687 6 6 theme high 731:734 arg1 oligosaccharides 760:775 high molecular weight sialyl oligosaccharides 731:775 high molecular weight sialyl oligosaccharides with repeating structures 731:801 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 6 7 with oligosaccharides 760:775 arg1 structures 792:801 repeating structures 782:801 repeating structures 782:801 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 1 8 theme female 122:127 arg1 infant 129:134 A female infant 120:134 A female infant presenting congenital ascites, hepatosplenomegaly, coarse face, and delayed mental and physical development 120:242 A female infant presenting congenital ascites, hepatosplenomegaly, coarse face, and delayed mental and physical development is described. 1502687 5 9 theme oligosaccharides 642:657 arg1 structures 620:629 The structures 616:629 The structures of urinary oligosaccharides 616:657 The structures of urinary oligosaccharides were the same as those of oligosaccharides in the ascites. 1502687 5 9 theme oligosaccharides 642:657 arg1 same 668:671 same 668:671 same 668:671 The structures of urinary oligosaccharides were the same as those of oligosaccharides in the ascites. 1502687 5 10 theme urinary 634:640 arg1 oligosaccharides 642:657 urinary oligosaccharides 634:657 urinary oligosaccharides 634:657 The structures of urinary oligosaccharides were the same as those of oligosaccharides in the ascites. 1502687 1 11 theme coarse 187:192 arg1 face 194:197 coarse face 187:197 coarse face 187:197 A female infant presenting congenital ascites, hepatosplenomegaly, coarse face, and delayed mental and physical development is described. 1502687 6 12 theme sialyl 827:832 arg1 oligosaccharides 834:849 sialyl oligosaccharides 827:849 low molecular weight sialyl oligosaccharides 806:849 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 3 13 theme oligosaccharides 403:418 arg1 times 474:478 25.8 times 469:478 25.8 times the levels of the controls 469:505 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. 1502687 3 13 theme oligosaccharides 403:418 arg1 level 386:390 The level 382:390 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient 382:463 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. 1502687 6 14 dep weight 820:825 arg1 oligosaccharides 834:849 sialyl oligosaccharides 827:849 low molecular weight sialyl oligosaccharides 806:849 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 0 15 theme Severe 0:5 arg1 characteristics 33:47 Severe infantile sialidosis--the characteristics 0:47 Severe infantile sialidosis--the characteristics of oligosaccharides 0:67 Severe infantile sialidosis--the characteristics of oligosaccharides isolated from the urine and the abdominal ascites. 1502687 6 16 theme molecular 810:818 arg1 weight 820:825 low molecular weight 806:825 low molecular weight sialyl oligosaccharides 806:849 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 2 17 theme patient 322:328 arg1 ascites 306:312 the abdominal ascites 292:312 the abdominal ascites of this patient 292:328 Oligosaccharides in the urine and the abdominal ascites of this patient were investigated by Bio-Gel column chromatography. 1502687 2 17 theme patient 322:328 arg1 Oligosaccharides 258:273 Oligosaccharides 258:273 Oligosaccharides in the urine 258:286 Oligosaccharides in the urine and the abdominal ascites of this patient were investigated by Bio-Gel column chromatography. 1502687 6 18 theme low 806:808 arg1 weight 820:825 low molecular weight 806:825 low molecular weight sialyl oligosaccharides 806:849 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 2 19 from Oligosaccharides 258:273 arg1 urine 282:286 the urine 278:286 the urine 278:286 Oligosaccharides in the urine and the abdominal ascites of this patient were investigated by Bio-Gel column chromatography. 1502687 1 20 theme delayed 204:210 arg1 development 232:242 delayed mental and physical development 204:242 delayed mental and physical development 204:242 A female infant presenting congenital ascites, hepatosplenomegaly, coarse face, and delayed mental and physical development is described. 1502687 3 21 theme urinary 395:401 arg1 oligosaccharides 403:418 urinary oligosaccharides 395:418 urinary oligosaccharides excreted (nmol/mg creatinine) 395:448 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. 1502687 3 21 theme urinary 395:401 arg1 creatinine 438:447 nmol/mg creatinine 430:447 nmol/mg creatinine 430:447 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. 1502687 1 22 theme mental 212:217 arg1 development 232:242 delayed mental and physical development 204:242 delayed mental and physical development 204:242 A female infant presenting congenital ascites, hepatosplenomegaly, coarse face, and delayed mental and physical development is described. 1502687 0 23 theme oligosaccharides 52:67 arg1 characteristics 33:47 Severe infantile sialidosis--the characteristics 0:47 Severe infantile sialidosis--the characteristics of oligosaccharides 0:67 Severe infantile sialidosis--the characteristics of oligosaccharides isolated from the urine and the abdominal ascites. 1502687 0 24 theme sialidosis--the 17:31 arg1 characteristics 33:47 Severe infantile sialidosis--the characteristics 0:47 Severe infantile sialidosis--the characteristics of oligosaccharides 0:67 Severe infantile sialidosis--the characteristics of oligosaccharides isolated from the urine and the abdominal ascites. 1502687 1 25 theme physical 223:230 arg1 development 232:242 delayed mental and physical development 204:242 delayed mental and physical development 204:242 A female infant presenting congenital ascites, hepatosplenomegaly, coarse face, and delayed mental and physical development is described. 1502687 5 26 from oligosaccharides 685:700 arg1 ascites 709:715 the ascites 705:715 the ascites 705:715 The structures of urinary oligosaccharides were the same as those of oligosaccharides in the ascites. 1502687 2 27 theme column 359:364 arg1 chromatography 366:379 Bio-Gel column chromatography 351:379 Bio-Gel column chromatography 351:379 Oligosaccharides in the urine and the abdominal ascites of this patient were investigated by Bio-Gel column chromatography. 1502687 3 28 theme controls 498:505 arg1 levels 484:489 the levels 480:489 25.8 times the levels of the controls 469:505 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. 1502687 3 29 theme nmol/mg 430:436 arg1 oligosaccharides 403:418 urinary oligosaccharides 395:418 urinary oligosaccharides excreted (nmol/mg creatinine) 395:448 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. 1502687 3 29 theme nmol/mg 430:436 arg1 creatinine 438:447 nmol/mg creatinine 430:447 nmol/mg creatinine 430:447 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. 1502687 6 30 theme repeating 782:790 arg1 structures 792:801 repeating structures 782:801 repeating structures 782:801 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 2 31 theme Bio-Gel 351:357 arg1 chromatography 366:379 Bio-Gel column chromatography 351:379 Bio-Gel column chromatography 351:379 Oligosaccharides in the urine and the abdominal ascites of this patient were investigated by Bio-Gel column chromatography. 1502687 3 32 dep times 474:478 arg1 levels 484:489 the levels 480:489 25.8 times the levels of the controls 469:505 The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. 1502687 6 33 theme oligosaccharides 760:775 arg1 ratio 722:726 The ratio 718:726 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides 718:849 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 6 33 theme oligosaccharides 760:775 arg1 higher 855:860 higher 855:860 higher 855:860 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 1 34 theme congenital 147:156 arg1 ascites 158:164 congenital ascites 147:164 congenital ascites 147:164 A female infant presenting congenital ascites, hepatosplenomegaly, coarse face, and delayed mental and physical development is described. 1502687 2 35 from ascites 306:312 arg1 urine 282:286 the urine 278:286 the urine 278:286 Oligosaccharides in the urine and the abdominal ascites of this patient were investigated by Bio-Gel column chromatography. 1502687 6 36 theme sialyl 753:758 arg1 oligosaccharides 760:775 high molecular weight sialyl oligosaccharides 731:775 high molecular weight sialyl oligosaccharides with repeating structures 731:801 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 1502687 0 37 dep Severe 0:5 arg1 infantile 7:15 infantile 7:15 infantile 7:15 Severe infantile sialidosis--the characteristics of oligosaccharides isolated from the urine and the abdominal ascites. 1502687 6 38 theme weight 746:751 arg1 oligosaccharides 760:775 high molecular weight sialyl oligosaccharides 731:775 high molecular weight sialyl oligosaccharides with repeating structures 731:801 The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine. 11425797 6 0 theme milk 948:951 arg1 fucosyloligosaccharides 953:975 milk fucosyloligosaccharides 948:975 milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype 948:1145 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 7 1 theme remaining 1173:1181 arg1 donors 1186:1191 the remaining 11 donors 1169:1191 the remaining 11 donors 1169:1191 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 6 2 theme donors 932:937 arg1 One 918:920 One 918:920 One 918:920 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 6 2 theme donors 932:937 arg1 donors 932:937 the 12 donors 925:937 the 12 donors 925:937 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 6 3 link alpha1,4-linked 1056:1070 arg1 fucose 1072:1077 alpha1,4-linked fucose 1056:1077 alpha1,4-linked fucose 1056:1077 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 6 3 link alpha1,4-linked 1056:1070 arg1 linkages 1018:1025 alpha1,2 linkages 1009:1025 alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) 1009:1078 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 7 4 theme milk 1151:1154 arg1 samples 1156:1162 milk samples 1151:1162 milk samples from the remaining 11 donors 1151:1191 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 5 5 theme weeks 900:904 arg1 postpartum 906:915 the first few weeks postpartum 886:915 the first few weeks postpartum 886:915 The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. 11425797 2 6 theme milk 339:342 arg1 samples 344:350 84 milk samples 336:350 84 milk samples 336:350 To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. 11425797 1 7 theme specific 210:217 arg1 pathogens 229:237 specific microbial pathogens 210:237 specific microbial pathogens 210:237 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 8 8 link alpha1,2-linked 1463:1477 arg1 fucose 1479:1484 alpha1,2-linked fucose 1463:1484 alpha1,2-linked fucose 1463:1484 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 11 9 theme milk 1962:1965 arg1 activities 1942:1951 the protective activities 1927:1951 the protective activities of human milk 1927:1965 This variation in individual oligosaccharide concentrations suggests that the protective activities of human milk could also vary among individuals and during lactation. 11425797 8 10 dep 1:1 1541:1543 arg1 to 1538:1539 to 1538:1539 to 1538:1539 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 1 11 gly fucosylated 148:158 arg1 oligosaccharides 168:183 especially fucosylated neutral oligosaccharides 137:183 especially fucosylated neutral oligosaccharides 137:183 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 1 11 gly fucosylated 148:158 arg1 oligosaccharides 119:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 9 12 theme individual 1607:1616 arg1 oligosaccharides 1618:1633 individual oligosaccharides 1607:1633 individual oligosaccharides 1607:1633 Furthermore, the absolute and the relative concentrations of individual oligosaccharides varied substantially, both between individual donors and over the course of lactation for each individual. 11425797 8 13 theme alpha1,2-linked 1386:1400 arg1 concentrations 1418:1431 alpha1,2-linked oligosaccharide concentrations 1386:1431 alpha1,2-linked oligosaccharide concentrations 1386:1431 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 5 14 theme total 747:751 arg1 concentration 753:765 The total concentration 743:765 The total concentration of oligosaccharides 743:785 The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. 11425797 7 15 link alpha1,2-linked 1229:1243 arg1 fucose 1245:1250 alpha1,2-linked fucose 1229:1250 alpha1,2-linked fucose 1229:1250 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 11 16 from variation 1858:1866 arg1 concentrations 1898:1911 individual oligosaccharide concentrations 1871:1911 individual oligosaccharide concentrations 1871:1911 This variation in individual oligosaccharide concentrations suggests that the protective activities of human milk could also vary among individuals and during lactation. 11425797 6 17 dep linkages 1018:1025 arg1 alpha1,3- 1042:1050 contained alpha1,3- 1032:1050 contained alpha1,3- 1032:1050 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 6 17 dep linkages 1018:1025 arg1 fucose 1072:1077 alpha1,4-linked fucose 1056:1077 alpha1,4-linked fucose 1056:1077 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 6 17 dep linkages 1018:1025 arg1 linkages 1018:1025 alpha1,2 linkages 1009:1025 alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) 1009:1078 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 8 18 theme concentrations 1418:1431 arg1 ratio 1377:1381 The ratio 1373:1381 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose 1373:1484 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 0 19 theme milk 18:21 arg1 oligosaccharides 23:38 Fucosylated human milk oligosaccharides 0:38 Fucosylated human milk oligosaccharides 0:38 Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. 11425797 1 20 theme neutral 160:166 arg1 oligosaccharides 168:183 especially fucosylated neutral oligosaccharides 137:183 especially fucosylated neutral oligosaccharides 137:183 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 1 20 theme neutral 160:166 arg1 oligosaccharides 119:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 6 21 theme alpha1,4-linked 1056:1070 arg1 fucose 1072:1077 alpha1,4-linked fucose 1056:1077 alpha1,4-linked fucose 1056:1077 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 6 21 theme alpha1,4-linked 1056:1070 arg1 linkages 1018:1025 alpha1,2 linkages 1009:1025 alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) 1009:1078 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 7 22 from donors 1186:1191 arg1 samples 1156:1162 milk samples 1151:1162 milk samples from the remaining 11 donors 1151:1191 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 5 23 theme mean 830:833 arg1 less 863:866 less 863:866 less 863:866 The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. 11425797 5 23 theme mean 830:833 arg1 concentration 835:847 the mean concentration 826:847 the mean concentration at 1 year 826:857 The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. 11425797 2 24 theme oligosaccharides 290:305 arg1 concentrations 253:266 the concentrations 249:266 the concentrations of individual neutral oligosaccharides 249:305 To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. 11425797 1 25 theme human 108:112 arg1 oligosaccharides 168:183 especially fucosylated neutral oligosaccharides 137:183 especially fucosylated neutral oligosaccharides 137:183 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 1 25 theme human 108:112 arg1 oligosaccharides 119:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 11 26 theme protective 1931:1940 arg1 activities 1942:1951 the protective activities 1927:1951 the protective activities of human milk 1927:1965 This variation in individual oligosaccharide concentrations suggests that the protective activities of human milk could also vary among individuals and during lactation. 11425797 0 27 theme lactation 88:96 arg1 course 78:83 the course 74:83 the course of lactation 74:96 Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. 11425797 8 28 theme fucose 1479:1484 arg1 devoid 1453:1458 devoid 1453:1458 devoid 1453:1458 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 0 29 theme Fucosylated 0:10 arg1 oligosaccharides 23:38 Fucosylated human milk oligosaccharides 0:38 Fucosylated human milk oligosaccharides 0:38 Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. 11425797 4 30 theme resultant 592:600 arg1 peaks 618:622 The resultant oligosaccharide peaks 588:622 The resultant oligosaccharide peaks 588:622 The resultant oligosaccharide peaks, identified by co-elution with authentic standards and mass spectrometry, ranged in size from tri- to octasaccharides. 11425797 8 31 theme first 1505:1509 arg1 year 1511:1514 the first year 1501:1514 the first year of lactation from 5:1 to 1:1 1501:1543 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 10 32 theme many 1823:1826 arg1 subpopulations 1837:1850 many genotype subpopulations 1823:1850 many genotype subpopulations 1823:1850 The patterns of milk oligosaccharides among individuals suggest the existence of many genotype subpopulations. 11425797 7 33 theme alpha1,2-linked 1229:1243 arg1 fucose 1245:1250 alpha1,2-linked fucose 1229:1250 alpha1,2-linked fucose 1229:1250 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 9 34 theme lactation 1711:1719 arg1 course 1701:1706 the course 1697:1706 the course of lactation for each individual 1697:1739 Furthermore, the absolute and the relative concentrations of individual oligosaccharides varied substantially, both between individual donors and over the course of lactation for each individual. 11425797 2 35 theme individual 271:280 arg1 oligosaccharides 290:305 individual neutral oligosaccharides 271:305 individual neutral oligosaccharides 271:305 To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. 11425797 11 36 theme oligosaccharide 1882:1896 arg1 concentrations 1898:1911 individual oligosaccharide concentrations 1871:1911 individual oligosaccharide concentrations 1871:1911 This variation in individual oligosaccharide concentrations suggests that the protective activities of human milk could also vary among individuals and during lactation. 11425797 10 37 theme subpopulations 1837:1850 arg1 existence 1810:1818 the existence 1806:1818 the existence of many genotype subpopulations 1806:1850 The patterns of milk oligosaccharides among individuals suggest the existence of many genotype subpopulations. 11425797 7 38 theme alpha1,2-linked 1349:1363 arg1 fucose 1365:1370 alpha1,2-linked fucose 1349:1370 alpha1,2-linked fucose 1349:1370 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 4 39 theme authentic 655:663 arg1 standards 665:673 authentic standards 655:673 authentic standards 655:673 The resultant oligosaccharide peaks, identified by co-elution with authentic standards and mass spectrometry, ranged in size from tri- to octasaccharides. 11425797 3 40 theme reversed-phase 533:546 arg1 chromatography 572:585 reversed-phase high-performance liquid chromatography 533:585 reversed-phase high-performance liquid chromatography 533:585 The neutral oligosaccharides from each sample were isolated, perbenzoylated, resolved, and quantified by reversed-phase high-performance liquid chromatography. 11425797 8 41 link alpha1,2-linked 1386:1400 arg1 concentrations 1418:1431 alpha1,2-linked oligosaccharide concentrations 1386:1431 alpha1,2-linked oligosaccharide concentrations 1386:1431 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 7 42 theme devoid 1339:1344 arg1 fucosyloligosaccharides 1315:1337 fucosyloligosaccharides 1315:1337 fucosyloligosaccharides devoid of alpha1,2-linked fucose 1315:1370 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 3 43 from sample 467:472 arg1 oligosaccharides 440:455 The neutral oligosaccharides 428:455 The neutral oligosaccharides from each sample 428:472 The neutral oligosaccharides from each sample were isolated, perbenzoylated, resolved, and quantified by reversed-phase high-performance liquid chromatography. 11425797 7 44 from those 1306:1310 arg1 distinct 1292:1299 distinct 1292:1299 distinct 1292:1299 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 7 45 contain containing 1218:1227 arg2 fucose 1245:1250 alpha1,2-linked fucose 1229:1250 alpha1,2-linked fucose 1229:1250 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 7 45 contain containing 1218:1227 arg1 fucosyloligosaccharides 1194:1216 fucosyloligosaccharides 1194:1216 fucosyloligosaccharides containing alpha1,2-linked fucose 1194:1250 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 3 46 theme liquid 565:570 arg1 chromatography 572:585 reversed-phase high-performance liquid chromatography 533:585 reversed-phase high-performance liquid chromatography 533:585 The neutral oligosaccharides from each sample were isolated, perbenzoylated, resolved, and quantified by reversed-phase high-performance liquid chromatography. 11425797 5 47 theme few 896:898 arg1 postpartum 906:915 the first few weeks postpartum 886:915 the first few weeks postpartum 886:915 The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. 11425797 6 48 from late 1086:1089 arg1 lactation 1094:1102 lactation 1094:1102 lactation 1094:1102 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 2 49 theme samples 344:350 arg1 total 327:331 a total 325:331 a total of 84 milk samples 325:350 To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. 11425797 6 50 from lactation 1094:1102 arg1 late 1086:1089 late 1086:1089 late 1086:1089 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 8 51 from 1:1 1541:1543 arg1 year 1511:1514 the first year 1501:1514 the first year of lactation from 5:1 to 1:1 1501:1543 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 1 52 theme microbial 219:227 arg1 pathogens 229:237 specific microbial pathogens 210:237 specific microbial pathogens 210:237 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 6 53 theme alpha1,2 1009:1016 arg1 alpha1,3- 1042:1050 contained alpha1,3- 1032:1050 contained alpha1,3- 1032:1050 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 6 53 theme alpha1,2 1009:1016 arg1 fucose 1072:1077 alpha1,4-linked fucose 1056:1077 alpha1,4-linked fucose 1056:1077 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 6 53 theme alpha1,2 1009:1016 arg1 linkages 1018:1025 alpha1,2 linkages 1009:1025 alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) 1009:1078 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 7 54 from prevalent 1257:1265 arg1 samples 1156:1162 milk samples 1151:1162 milk samples from the remaining 11 donors 1151:1191 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 10 55 theme milk 1758:1761 arg1 oligosaccharides 1763:1778 milk oligosaccharides 1758:1778 milk oligosaccharides 1758:1778 The patterns of milk oligosaccharides among individuals suggest the existence of many genotype subpopulations. 11425797 5 56 theme oligosaccharides 770:785 arg1 concentration 753:765 The total concentration 743:765 The total concentration of oligosaccharides 743:785 The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. 11425797 9 57 theme relative 1580:1587 arg1 concentrations 1589:1602 the relative concentrations 1576:1602 the relative concentrations of individual oligosaccharides 1576:1633 Furthermore, the absolute and the relative concentrations of individual oligosaccharides varied substantially, both between individual donors and over the course of lactation for each individual. 11425797 6 58 theme linkages 1018:1025 arg1 devoid 999:1004 devoid 999:1004 devoid 999:1004 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 1 59 theme milk 114:117 arg1 oligosaccharides 168:183 especially fucosylated neutral oligosaccharides 137:183 especially fucosylated neutral oligosaccharides 137:183 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 1 59 theme milk 114:117 arg1 oligosaccharides 119:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 7 60 link alpha1,2-linked 1349:1363 arg1 fucose 1365:1370 alpha1,2-linked fucose 1349:1370 alpha1,2-linked fucose 1349:1370 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 9 61 theme oligosaccharides 1618:1633 arg1 concentrations 1589:1602 the relative concentrations 1576:1602 the relative concentrations of individual oligosaccharides 1576:1633 Furthermore, the absolute and the relative concentrations of individual oligosaccharides varied substantially, both between individual donors and over the course of lactation for each individual. 11425797 5 62 theme lactation 815:823 arg1 course 805:810 the course 801:810 the course of lactation 801:823 The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. 11425797 2 63 theme neutral 282:288 arg1 oligosaccharides 290:305 individual neutral oligosaccharides 271:305 individual neutral oligosaccharides 271:305 To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. 11425797 1 64 theme fucosylated 148:158 arg1 oligosaccharides 168:183 especially fucosylated neutral oligosaccharides 137:183 especially fucosylated neutral oligosaccharides 137:183 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 1 64 theme fucosylated 148:158 arg1 oligosaccharides 119:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 8 65 theme oligosaccharide 1402:1416 arg1 concentrations 1418:1431 alpha1,2-linked oligosaccharide concentrations 1386:1431 alpha1,2-linked oligosaccharide concentrations 1386:1431 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 5 66 from year 854:857 arg1 less 863:866 less 863:866 less 863:866 The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. 11425797 5 66 from year 854:857 arg1 concentration 835:847 the mean concentration 826:847 the mean concentration at 1 year 826:857 The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. 11425797 11 67 theme human 1956:1960 arg1 milk 1962:1965 human milk 1956:1965 human milk 1956:1965 This variation in individual oligosaccharide concentrations suggests that the protective activities of human milk could also vary among individuals and during lactation. 11425797 9 68 theme individual 1670:1679 arg1 donors 1681:1686 individual donors 1670:1686 individual donors 1670:1686 Furthermore, the absolute and the relative concentrations of individual oligosaccharides varied substantially, both between individual donors and over the course of lactation for each individual. 11425797 6 69 theme contained 1032:1040 arg1 alpha1,3- 1042:1050 contained alpha1,3- 1032:1050 contained alpha1,3- 1032:1050 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 6 69 theme contained 1032:1040 arg1 linkages 1018:1025 alpha1,2 linkages 1009:1025 alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) 1009:1078 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 8 70 theme devoid 1453:1458 arg1 oligosaccharides 1436:1451 oligosaccharides 1436:1451 oligosaccharides devoid of alpha1,2-linked fucose 1436:1484 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 6 71 theme nonsecretor 1125:1135 arg1 phenotype 1137:1145 the nonsecretor phenotype 1121:1145 the nonsecretor phenotype 1121:1145 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 8 72 theme alpha1,2-linked 1463:1477 arg1 fucose 1479:1484 alpha1,2-linked fucose 1463:1484 alpha1,2-linked fucose 1463:1484 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 2 73 theme weeks 405:409 arg1 postpartum 416:425 weeks 1-49 postpartum 405:425 weeks 1-49 postpartum 405:425 To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. 11425797 0 74 theme human 12:16 arg1 oligosaccharides 23:38 Fucosylated human milk oligosaccharides 0:38 Fucosylated human milk oligosaccharides 0:38 Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. 11425797 4 75 theme oligosaccharide 602:616 arg1 peaks 618:622 The resultant oligosaccharide peaks 588:622 The resultant oligosaccharide peaks 588:622 The resultant oligosaccharide peaks, identified by co-elution with authentic standards and mass spectrometry, ranged in size from tri- to octasaccharides. 11425797 10 76 theme oligosaccharides 1763:1778 arg1 patterns 1746:1753 The patterns 1742:1753 The patterns of milk oligosaccharides among individuals 1742:1796 The patterns of milk oligosaccharides among individuals suggest the existence of many genotype subpopulations. 11425797 1 77 theme Specific 99:106 arg1 oligosaccharides 168:183 especially fucosylated neutral oligosaccharides 137:183 especially fucosylated neutral oligosaccharides 137:183 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 1 77 theme Specific 99:106 arg1 oligosaccharides 119:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides 99:134 Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. 11425797 2 78 theme time 385:388 arg1 periods 390:396 7 time periods 383:396 7 time periods 383:396 To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. 11425797 6 79 with consistent 1105:1114 arg1 phenotype 1137:1145 the nonsecretor phenotype 1121:1145 the nonsecretor phenotype 1121:1145 One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. 11425797 3 80 theme neutral 432:438 arg1 oligosaccharides 440:455 The neutral oligosaccharides 428:455 The neutral oligosaccharides from each sample 428:472 The neutral oligosaccharides from each sample were isolated, perbenzoylated, resolved, and quantified by reversed-phase high-performance liquid chromatography. 11425797 7 81 from samples 1156:1162 arg1 prevalent 1257:1265 prevalent 1257:1265 prevalent 1257:1265 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 2 82 from periods 390:396 arg1 women 374:378 12 women 371:378 12 women at 7 time periods 371:396 To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. 11425797 7 83 theme fucose 1365:1370 arg1 devoid 1339:1344 devoid 1339:1344 devoid 1339:1344 In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. 11425797 11 84 theme individual 1871:1880 arg1 concentrations 1898:1911 individual oligosaccharide concentrations 1871:1911 individual oligosaccharide concentrations 1871:1911 This variation in individual oligosaccharide concentrations suggests that the protective activities of human milk could also vary among individuals and during lactation. 11425797 8 85 theme lactation 1519:1527 arg1 year 1511:1514 the first year 1501:1514 the first year of lactation from 5:1 to 1:1 1501:1543 The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. 11425797 10 86 theme genotype 1828:1835 arg1 subpopulations 1837:1850 many genotype subpopulations 1823:1850 many genotype subpopulations 1823:1850 The patterns of milk oligosaccharides among individuals suggest the existence of many genotype subpopulations. 11425797 4 87 theme mass 679:682 arg1 spectrometry 684:695 mass spectrometry 679:695 mass spectrometry 679:695 The resultant oligosaccharide peaks, identified by co-elution with authentic standards and mass spectrometry, ranged in size from tri- to octasaccharides. 11425797 3 88 theme high-performance 548:563 arg1 chromatography 572:585 reversed-phase high-performance liquid chromatography 533:585 reversed-phase high-performance liquid chromatography 533:585 The neutral oligosaccharides from each sample were isolated, perbenzoylated, resolved, and quantified by reversed-phase high-performance liquid chromatography. 11787698 13 0 gly fucosylated 1899:1909 arg1 oligosaccharides 1911:1926 neutral fucosylated oligosaccharides 1891:1926 neutral fucosylated oligosaccharides 1891:1926 This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. 11787698 12 1 theme milk 1683:1686 arg1 specimens 1688:1696 milk specimens 1683:1696 milk specimens from the other species studied 1683:1727 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 10 2 theme oligosaccharides 1428:1443 arg1 many 1446:1449 many 1446:1449 many 1446:1449 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 10 2 theme oligosaccharides 1428:1443 arg1 oligosaccharides 1428:1443 oligosaccharides 1428:1443 oligosaccharides 1428:1443 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 10 2 theme oligosaccharides 1428:1443 arg1 range 1419:1423 a wide range 1412:1423 a wide range of oligosaccharides, many of which had novel, fucosylated structures 1412:1492 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 9 3 contain had 1295:1297 arg2 oligosaccharides 1303:1318 few oligosaccharides 1299:1318 few oligosaccharides in their milk other than 2'-fucosyllactose 1299:1361 Marine mammals generally had few oligosaccharides in their milk other than 2'-fucosyllactose. 11787698 9 3 contain had 1295:1297 arg1 mammals 1277:1283 Marine mammals 1270:1283 Marine mammals 1270:1283 Marine mammals generally had few oligosaccharides in their milk other than 2'-fucosyllactose. 11787698 11 4 dep complex 1588:1594 arg1 neutral 1597:1603 neutral 1597:1603 neutral 1597:1603 Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. 11787698 7 5 from types 988:992 arg1 specimens 1022:1030 milk specimens 1017:1030 milk specimens from the primates 1017:1048 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 3 6 from variety 587:593 arg1 apes 627:630 the great apes 617:630 the great apes 617:630 Toward this end, a comparison was made of the major individual oligosaccharides in milk specimens from a variety of species, including the great apes. 11787698 3 6 from variety 587:593 arg1 specimens 570:578 milk specimens 565:578 milk specimens 565:578 Toward this end, a comparison was made of the major individual oligosaccharides in milk specimens from a variety of species, including the great apes. 11787698 11 7 theme greatest 1553:1560 arg1 quantity 1562:1569 the greatest quantity 1549:1569 the greatest quantity of, and the most complex, neutral oligosaccharides 1549:1620 Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. 11787698 1 8 gly fucosylated 165:175 arg1 most 147:150 most 147:150 most 147:150 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 1 8 gly fucosylated 165:175 arg1 amounts 113:119 large amounts 107:119 large amounts 107:119 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 1 8 gly fucosylated 165:175 arg1 oligosaccharides 129:144 many oligosaccharides 124:144 many oligosaccharides 124:144 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 13 9 theme milk 1857:1860 arg1 specimens 1862:1870 animal milk specimens 1850:1870 animal milk specimens 1850:1870 This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. 11787698 5 10 theme Ambiguous 829:837 arg1 structures 839:848 Ambiguous structures 829:848 Ambiguous structures 829:848 Ambiguous structures were determined by mass spectrometry. 11787698 4 11 theme liquid 776:781 arg1 chromatography 783:796 high performance liquid chromatography 759:796 high performance liquid chromatography (HPLC) 759:803 The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. 11787698 4 11 theme liquid 776:781 arg1 HPLC 799:802 HPLC 799:802 HPLC 799:802 The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. 11787698 12 12 theme more 1653:1656 arg1 oligosaccharide 1658:1672 more oligosaccharide 1653:1672 more oligosaccharide 1653:1672 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 9 13 theme other 1334:1338 arg1 milk 1329:1332 their milk 1323:1332 their milk other than 2'-fucosyllactose 1323:1361 Marine mammals generally had few oligosaccharides in their milk other than 2'-fucosyllactose. 11787698 6 14 from milk 978:981 arg1 low 953:955 low 953:955 low 953:955 All milk specimens contained lactose, although levels were quite low in bear and kangaroo milk. 11787698 1 15 theme Human 87:91 arg1 milk 93:96 Human milk 87:96 Human milk 87:96 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 5 16 theme mass 869:872 arg1 spectrometry 874:885 mass spectrometry 869:885 mass spectrometry 869:885 Ambiguous structures were determined by mass spectrometry. 11787698 2 17 theme bovine 274:279 arg1 milk 281:284 bovine milk 274:284 bovine milk 274:284 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 8 18 theme oligosaccharides 1179:1194 arg1 amounts 1168:1174 The relative amounts 1155:1174 The relative amounts of oligosaccharides in the bonobo 1155:1208 The relative amounts of oligosaccharides in the bonobo changed over the course of lactation, as they do in humans. 11787698 8 18 theme oligosaccharides 1179:1194 arg1 oligosaccharides 1179:1194 oligosaccharides 1179:1194 oligosaccharides 1179:1194 The relative amounts of oligosaccharides in the bonobo changed over the course of lactation, as they do in humans. 11787698 1 19 contain contains 98:105 arg1 milk 93:96 Human milk 87:96 Human milk 87:96 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 1 19 contain contains 98:105 arg2 oligosaccharides 129:144 many oligosaccharides 124:144 many oligosaccharides 124:144 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 1 19 contain contains 98:105 arg2 amounts 113:119 large amounts 107:119 large amounts 107:119 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 10 20 dep novel 1464:1468 arg1 fucosylated 1471:1481 fucosylated 1471:1481 fucosylated 1471:1481 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 13 21 from pathogens 1962:1970 arg1 protection 1946:1955 protection 1946:1955 protection from pathogens 1946:1970 This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. 11787698 3 22 theme major 528:532 arg1 oligosaccharides 545:560 the major individual oligosaccharides 524:560 the major individual oligosaccharides 524:560 Toward this end, a comparison was made of the major individual oligosaccharides in milk specimens from a variety of species, including the great apes. 11787698 13 23 theme immune 1999:2004 arg1 systems 2006:2012 immature immune systems 1990:2012 immature immune systems 1990:2012 This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. 11787698 10 24 contain contained 1402:1410 arg1 specimens 1392:1400 Grizzly and black bear milk specimens 1364:1400 Grizzly and black bear milk specimens 1364:1400 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 10 24 contain contained 1402:1410 arg2 range 1419:1423 a wide range 1412:1423 a wide range of oligosaccharides, many of which had novel, fucosylated structures 1412:1492 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 11 25 theme oligosaccharides 1605:1620 arg1 quantity 1562:1569 the greatest quantity 1549:1569 the greatest quantity of, and the most complex, neutral oligosaccharides 1549:1620 Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. 11787698 3 26 theme milk 565:568 arg1 apes 627:630 the great apes 617:630 the great apes 617:630 Toward this end, a comparison was made of the major individual oligosaccharides in milk specimens from a variety of species, including the great apes. 11787698 3 26 theme milk 565:568 arg1 specimens 570:578 milk specimens 565:578 milk specimens 565:578 Toward this end, a comparison was made of the major individual oligosaccharides in milk specimens from a variety of species, including the great apes. 11787698 8 27 from amounts 1168:1174 arg1 bonobo 1203:1208 the bonobo 1199:1208 the bonobo 1199:1208 The relative amounts of oligosaccharides in the bonobo changed over the course of lactation, as they do in humans. 11787698 10 28 theme novel 1464:1468 arg1 structures 1483:1492 novel, fucosylated structures 1464:1492 novel, fucosylated structures 1464:1492 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 4 29 theme neutral 637:643 arg1 compounds 645:653 The neutral compounds 633:653 The neutral compounds 633:653 The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. 11787698 0 30 theme other 72:76 arg1 species 78:84 twelve other species 65:84 twelve other species 65:84 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 11787698 0 31 from Comparison 0:9 arg1 specimens 39:47 milk specimens 34:47 milk specimens from humans and twelve other species 34:84 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 11787698 0 31 from Comparison 0:9 arg1 species 78:84 twelve other species 65:84 twelve other species 65:84 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 11787698 0 31 from Comparison 0:9 arg1 humans 54:59 humans 54:59 humans 54:59 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 11787698 2 32 dep many 317:320 arg1 fewer 322:326 fewer 322:326 fewer 322:326 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 1 33 theme many 124:127 arg1 oligosaccharides 129:144 many oligosaccharides 124:144 many oligosaccharides 124:144 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 10 34 theme black 1376:1380 arg1 specimens 1392:1400 Grizzly and black bear milk specimens 1364:1400 Grizzly and black bear milk specimens 1364:1400 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 12 35 theme complex 1769:1775 arg1 oligosaccharides 1777:1792 complex oligosaccharides 1769:1792 complex oligosaccharides 1769:1792 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 10 36 theme Grizzly 1364:1370 arg1 specimens 1392:1400 Grizzly and black bear milk specimens 1364:1400 Grizzly and black bear milk specimens 1364:1400 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 2 37 theme oligosaccharides 337:352 arg1 types 328:332 much less and many fewer types 303:332 much less and many fewer types of oligosaccharides 303:352 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 2 38 dep amount 404:409 arg1 the 400:402 the 400:402 the 400:402 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 4 39 from bulk 676:679 arg1 milk 710:713 human milk 704:713 human milk 704:713 The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. 11787698 10 40 contain had 1460:1462 arg1 many 1446:1449 many 1446:1449 many 1446:1449 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 10 40 contain had 1460:1462 arg1 oligosaccharides 1428:1443 oligosaccharides 1428:1443 oligosaccharides 1428:1443 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 10 40 contain had 1460:1462 arg2 structures 1483:1492 novel, fucosylated structures 1464:1492 novel, fucosylated structures 1464:1492 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 4 41 theme oligosaccharides 684:699 arg1 bulk 676:679 the bulk 672:679 the bulk of oligosaccharides in human milk 672:713 The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. 11787698 0 42 theme oligosaccharides 14:29 arg1 Comparison 0:9 Comparison 0:9 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 0:85 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 11787698 2 43 theme milk 434:437 arg1 oligosaccharides 439:454 human milk oligosaccharides 428:454 human milk oligosaccharides 428:454 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 7 44 from specimens 1022:1030 arg1 types 988:992 The types 984:992 The types of oligosaccharides in milk specimens from the primates 984:1048 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 10 45 theme milk 1387:1390 arg1 specimens 1392:1400 Grizzly and black bear milk specimens 1364:1400 Grizzly and black bear milk specimens 1364:1400 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 3 46 theme species 598:604 arg1 species 598:604 species 598:604 species 598:604 Toward this end, a comparison was made of the major individual oligosaccharides in milk specimens from a variety of species, including the great apes. 11787698 3 46 theme species 598:604 arg1 variety 587:593 a variety 585:593 a variety of species 585:604 Toward this end, a comparison was made of the major individual oligosaccharides in milk specimens from a variety of species, including the great apes. 11787698 0 47 theme milk 34:37 arg1 specimens 39:47 milk specimens 34:47 milk specimens from humans and twelve other species 34:84 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 11787698 12 48 theme amounts 1758:1764 arg1 presence 1734:1741 the presence 1730:1741 the presence of appreciable amounts of complex oligosaccharides 1730:1792 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 12 48 theme amounts 1758:1764 arg1 unique 1802:1807 unique 1802:1807 unique 1802:1807 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 4 49 theme high 759:762 arg1 chromatography 783:796 high performance liquid chromatography 759:796 high performance liquid chromatography (HPLC) 759:803 The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. 11787698 4 49 theme high 759:762 arg1 HPLC 799:802 HPLC 799:802 HPLC 799:802 The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. 11787698 11 50 theme Milk 1495:1498 arg1 specimens 1500:1508 Milk specimens 1495:1508 Milk specimens from humans, bears, and marsupials 1495:1543 Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. 11787698 2 51 theme less 308:311 arg1 types 328:332 much less and many fewer types 303:332 much less and many fewer types of oligosaccharides 303:352 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 9 52 from oligosaccharides 1303:1318 arg1 milk 1329:1332 their milk 1323:1332 their milk other than 2'-fucosyllactose 1323:1361 Marine mammals generally had few oligosaccharides in their milk other than 2'-fucosyllactose. 11787698 10 53 theme wide 1414:1417 arg1 range 1419:1423 a wide range 1412:1423 a wide range of oligosaccharides, many of which had novel, fucosylated structures 1412:1492 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 3 54 theme great 621:625 arg1 apes 627:630 the great apes 617:630 the great apes 617:630 Toward this end, a comparison was made of the major individual oligosaccharides in milk specimens from a variety of species, including the great apes. 11787698 13 55 theme fucosylated 1899:1909 arg1 oligosaccharides 1911:1926 neutral fucosylated oligosaccharides 1891:1926 neutral fucosylated oligosaccharides 1891:1926 This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. 11787698 9 56 theme Marine 1270:1275 arg1 mammals 1277:1283 Marine mammals 1270:1283 Marine mammals 1270:1283 Marine mammals generally had few oligosaccharides in their milk other than 2'-fucosyllactose. 11787698 11 57 theme complex 1588:1594 arg1 oligosaccharides 1605:1620 and the most complex, neutral oligosaccharides 1575:1620 oligosaccharides 1605:1620 Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. 11787698 13 58 theme human 1879:1883 arg1 milk 1885:1888 human milk 1879:1888 human milk 1879:1888 This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. 11787698 2 59 theme many 317:320 arg1 types 328:332 much less and many fewer types 303:332 much less and many fewer types of oligosaccharides 303:352 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 9 60 theme few 1299:1301 arg1 oligosaccharides 1303:1318 few oligosaccharides 1299:1318 few oligosaccharides in their milk other than 2'-fucosyllactose 1299:1361 Marine mammals generally had few oligosaccharides in their milk other than 2'-fucosyllactose. 11787698 13 61 theme animal 1850:1855 arg1 specimens 1862:1870 animal milk specimens 1850:1870 animal milk specimens 1850:1870 This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. 11787698 7 62 theme milk 1017:1020 arg1 specimens 1022:1030 milk specimens 1017:1030 milk specimens from the primates 1017:1048 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 4 63 theme performance 764:774 arg1 chromatography 783:796 high performance liquid chromatography 759:796 high performance liquid chromatography (HPLC) 759:803 The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. 11787698 4 63 theme performance 764:774 arg1 HPLC 799:802 HPLC 799:802 HPLC 799:802 The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. 11787698 7 64 theme molecules 1123:1131 arg1 molecules 1123:1131 the larger molecules 1112:1131 the larger molecules 1112:1131 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 7 64 theme molecules 1123:1131 arg1 lower 1148:1152 lower 1148:1152 lower 1148:1152 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 7 64 theme molecules 1123:1131 arg1 amounts 1089:1095 the amounts 1085:1095 the amounts 1085:1095 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 7 65 theme oligosaccharides 997:1012 arg1 types 988:992 The types 984:992 The types of oligosaccharides in milk specimens from the primates 984:1048 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 6 66 from bear 960:963 arg1 low 953:955 low 953:955 low 953:955 All milk specimens contained lactose, although levels were quite low in bear and kangaroo milk. 11787698 11 67 from humans 1515:1520 arg1 specimens 1500:1508 Milk specimens 1495:1508 Milk specimens from humans, bears, and marsupials 1495:1543 Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. 11787698 12 68 theme human 1632:1636 arg1 milk 1638:1641 human milk 1632:1641 human milk 1632:1641 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 6 69 theme milk 892:895 arg1 specimens 897:905 All milk specimens 888:905 All milk specimens 888:905 All milk specimens contained lactose, although levels were quite low in bear and kangaroo milk. 11787698 0 70 from species 78:84 arg1 specimens 39:47 milk specimens 34:47 milk specimens from humans and twelve other species 34:84 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 11787698 0 70 from species 78:84 arg1 Comparison 0:9 Comparison 0:9 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 0:85 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 11787698 8 71 theme relative 1159:1166 arg1 amounts 1168:1174 The relative amounts 1155:1174 The relative amounts of oligosaccharides in the bonobo 1155:1208 The relative amounts of oligosaccharides in the bonobo changed over the course of lactation, as they do in humans. 11787698 8 71 theme relative 1159:1166 arg1 oligosaccharides 1179:1194 oligosaccharides 1179:1194 oligosaccharides 1179:1194 The relative amounts of oligosaccharides in the bonobo changed over the course of lactation, as they do in humans. 11787698 3 72 theme individual 534:543 arg1 oligosaccharides 545:560 the major individual oligosaccharides 524:560 the major individual oligosaccharides 524:560 Toward this end, a comparison was made of the major individual oligosaccharides in milk specimens from a variety of species, including the great apes. 11787698 1 73 theme pathogenic 194:203 arg1 bacteria 205:212 pathogenic bacteria 194:212 pathogenic bacteria 194:212 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 1 74 theme large 107:111 arg1 amounts 113:119 large amounts 107:119 large amounts 107:119 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 1 74 theme large 107:111 arg1 oligosaccharides 129:144 many oligosaccharides 124:144 many oligosaccharides 124:144 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 13 75 theme immature 1990:1997 arg1 systems 2006:2012 immature immune systems 1990:2012 immature immune systems 1990:2012 This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. 11787698 4 76 theme human 704:708 arg1 milk 710:713 human milk 704:713 human milk 704:713 The neutral compounds, which represent the bulk of oligosaccharides in human milk, were isolated, perbenzoylated, resolved by high performance liquid chromatography (HPLC), and detected at 229nm. 11787698 1 77 theme oligosaccharides 129:144 arg1 amounts 113:119 large amounts 107:119 large amounts 107:119 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 1 77 theme oligosaccharides 129:144 arg1 oligosaccharides 129:144 many oligosaccharides 124:144 many oligosaccharides 124:144 Human milk contains large amounts of many oligosaccharides, most of which are fucosylated; several inhibit pathogenic bacteria, viruses, and toxins that cause disease in humans. 11787698 7 78 theme larger 1116:1121 arg1 molecules 1123:1131 the larger molecules 1112:1131 the larger molecules 1112:1131 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 2 79 contain have 298:301 arg2 types 328:332 much less and many fewer types 303:332 much less and many fewer types of oligosaccharides 303:352 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 2 79 contain have 298:301 arg1 milk 281:284 bovine milk 274:284 bovine milk 274:284 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 13 80 with offspring 1975:1983 arg1 systems 2006:2012 immature immune systems 1990:2012 immature immune systems 1990:2012 This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. 11787698 2 81 theme oligosaccharides 439:454 arg1 amount 404:409 amount 404:409 amount 404:409 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 2 81 theme oligosaccharides 439:454 arg1 oligosaccharides 439:454 human milk oligosaccharides 428:454 human milk oligosaccharides 428:454 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 2 81 theme oligosaccharides 439:454 arg1 complexity 414:423 complexity 414:423 complexity 414:423 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 0 82 from humans 54:59 arg1 specimens 39:47 milk specimens 34:47 milk specimens from humans and twelve other species 34:84 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 11787698 0 82 from humans 54:59 arg1 Comparison 0:9 Comparison 0:9 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 0:85 Comparison of oligosaccharides in milk specimens from humans and twelve other species. 11787698 6 83 from low 953:955 arg1 bear 960:963 bear 960:963 bear 960:963 All milk specimens contained lactose, although levels were quite low in bear and kangaroo milk. 11787698 6 83 from low 953:955 arg1 milk 978:981 milk 978:981 milk 978:981 All milk specimens contained lactose, although levels were quite low in bear and kangaroo milk. 11787698 8 84 theme lactation 1237:1245 arg1 course 1227:1232 the course 1223:1232 the course of lactation 1223:1245 The relative amounts of oligosaccharides in the bonobo changed over the course of lactation, as they do in humans. 11787698 12 85 contain contained 1643:1651 arg2 oligosaccharide 1658:1672 more oligosaccharide 1653:1672 more oligosaccharide 1653:1672 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 12 85 contain contained 1643:1651 arg1 milk 1638:1641 human milk 1632:1641 human milk 1632:1641 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 12 86 theme oligosaccharides 1777:1792 arg1 amounts 1758:1764 appreciable amounts 1746:1764 appreciable amounts of complex oligosaccharides 1746:1792 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 12 86 theme oligosaccharides 1777:1792 arg1 oligosaccharides 1777:1792 complex oligosaccharides 1769:1792 complex oligosaccharides 1769:1792 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 11 87 contain had 1545:1547 arg2 quantity 1562:1569 the greatest quantity 1549:1569 the greatest quantity of, and the most complex, neutral oligosaccharides 1549:1620 Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. 11787698 11 87 contain had 1545:1547 arg1 specimens 1500:1508 Milk specimens 1495:1508 Milk specimens from humans, bears, and marsupials 1495:1543 Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. 11787698 12 88 dep did 1679:1681 arg1 than 1674:1677 than 1674:1677 than 1674:1677 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 11 89 from bears 1523:1527 arg1 specimens 1500:1508 Milk specimens 1495:1508 Milk specimens from humans, bears, and marsupials 1495:1543 Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. 11787698 7 90 from oligosaccharides 997:1012 arg1 specimens 1022:1030 milk specimens 1017:1030 milk specimens from the primates 1017:1048 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 7 90 from oligosaccharides 997:1012 arg1 primates 1041:1048 the primates 1037:1048 the primates 1037:1048 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 12 91 theme appreciable 1746:1756 arg1 amounts 1758:1764 appreciable amounts 1746:1764 appreciable amounts of complex oligosaccharides 1746:1792 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 12 91 theme appreciable 1746:1756 arg1 oligosaccharides 1777:1792 complex oligosaccharides 1769:1792 complex oligosaccharides 1769:1792 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 7 92 theme human 1069:1073 arg1 milk 1075:1078 human milk 1069:1078 human milk 1069:1078 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 2 93 theme human 428:432 arg1 oligosaccharides 439:454 human milk oligosaccharides 428:454 human milk oligosaccharides 428:454 Although bovine milk is known to have much less and many fewer types of oligosaccharides, no studies heretofore have indicated whether the amount or complexity of human milk oligosaccharides is unique to our species. 11787698 10 94 theme bear 1382:1385 arg1 specimens 1392:1400 Grizzly and black bear milk specimens 1364:1400 Grizzly and black bear milk specimens 1364:1400 Grizzly and black bear milk specimens contained a wide range of oligosaccharides, many of which had novel, fucosylated structures. 11787698 12 95 from species 1713:1719 arg1 specimens 1688:1696 milk specimens 1683:1696 milk specimens from the other species studied 1683:1727 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 11787698 11 96 from marsupials 1534:1543 arg1 specimens 1500:1508 Milk specimens 1495:1508 Milk specimens from humans, bears, and marsupials 1495:1543 Milk specimens from humans, bears, and marsupials had the greatest quantity of, and the most complex, neutral oligosaccharides. 11787698 7 97 from primates 1041:1048 arg1 oligosaccharides 997:1012 oligosaccharides 997:1012 oligosaccharides in milk specimens from the primates 997:1048 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 7 97 from primates 1041:1048 arg1 specimens 1022:1030 milk specimens 1017:1030 milk specimens from the primates 1017:1048 The types of oligosaccharides in milk specimens from the primates resembled those of human milk, but the amounts, especially of the larger molecules, were markedly lower. 11787698 6 98 contain contained 907:915 arg2 lactose 917:923 lactose 917:923 lactose 917:923 All milk specimens contained lactose, although levels were quite low in bear and kangaroo milk. 11787698 6 98 contain contained 907:915 arg1 specimens 897:905 All milk specimens 888:905 All milk specimens 888:905 All milk specimens contained lactose, although levels were quite low in bear and kangaroo milk. 11787698 13 99 theme neutral 1891:1897 arg1 oligosaccharides 1911:1926 neutral fucosylated oligosaccharides 1891:1926 neutral fucosylated oligosaccharides 1891:1926 This finding suggests that in animal milk specimens, as in human milk, neutral fucosylated oligosaccharides potentially offer protection from pathogens to offspring with immature immune systems. 11787698 12 100 theme other 1707:1711 arg1 species 1713:1719 the other species 1703:1719 the other species studied 1703:1727 Although human milk contained more oligosaccharide than did milk specimens from the other species studied, the presence of appreciable amounts of complex oligosaccharides was not unique to humans. 26613816 3 0 theme pure 633:636 arg1 forms 638:642 their pure forms 627:642 their pure forms 627:642 This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. 26613816 7 1 theme HMOS-based 1383:1392 arg1 prebiotics 1411:1420 HMOS-based or HMOS-inspired prebiotics 1383:1420 HMOS-based or HMOS-inspired prebiotics 1383:1420 Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics. 26613816 5 2 theme desired 1030:1036 arg1 functions 1038:1046 desired functions 1030:1046 desired functions 1030:1046 This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. 26613816 4 3 theme chemoenzymatic 695:708 arg1 systems 739:745 enzymatic, chemoenzymatic, whole-cell, and living-cell systems 684:745 enzymatic, chemoenzymatic, whole-cell, and living-cell systems 684:745 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 2 4 theme antiadhesive 415:426 arg1 antimicrobials 428:441 antiadhesive antimicrobials 415:441 antiadhesive antimicrobials 415:441 Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. 26613816 3 5 theme HMOS 619:622 arg1 amounts 597:603 large amounts 591:603 large amounts of individual HMOS 591:622 This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. 26613816 3 5 theme HMOS 619:622 arg1 HMOS 619:622 individual HMOS 608:622 individual HMOS 608:622 This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. 26613816 4 6 theme number 785:790 arg1 production 761:770 the production 757:770 the production of a growing number of HMOS in increasing amounts 757:820 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 5 7 theme HMOS 901:904 arg1 roles 892:896 the important roles 878:896 the important roles of HMOS 878:904 This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. 26613816 4 8 theme whole-cell 711:720 arg1 systems 739:745 enzymatic, chemoenzymatic, whole-cell, and living-cell systems 684:745 enzymatic, chemoenzymatic, whole-cell, and living-cell systems 684:745 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 7 9 theme HMOS 1289:1292 arg1 structures 1262:1271 the structures 1258:1271 the structures of more complex HMOS 1258:1292 Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics. 26613816 6 10 theme enzyme-catalyzed 1080:1095 arg1 synthesis 1097:1105 enzyme-catalyzed synthesis 1080:1105 enzyme-catalyzed synthesis 1080:1105 The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. 26613816 5 11 theme important 882:890 arg1 roles 892:896 the important roles 878:896 the important roles of HMOS 878:904 This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. 26613816 6 12 from progress 1183:1190 arg1 aspects 1201:1207 these aspects 1195:1207 these aspects 1195:1207 The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. 26613816 0 13 theme Enzyme-Catalyzed 61:76 arg1 Oligosaccharides 11:26 Human Milk Oligosaccharides 0:26 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 0:87 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 13 theme Enzyme-Catalyzed 61:76 arg1 Synthesis 78:86 Enzyme-Catalyzed Synthesis 61:86 Enzyme-Catalyzed Synthesis 61:86 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 5 14 theme defined 1006:1012 arg1 structures 1014:1023 defined structures 1006:1023 defined structures with desired functions 1006:1046 This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. 26613816 4 15 theme HMOS 795:798 arg1 number 785:790 a growing number 775:790 a growing number of HMOS 775:798 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 4 16 theme enzymatic 684:692 arg1 systems 739:745 enzymatic, chemoenzymatic, whole-cell, and living-cell systems 684:745 enzymatic, chemoenzymatic, whole-cell, and living-cell systems 684:745 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 1 17 theme breast-fed 213:222 arg1 infants 224:230 breast-fed infants 213:230 breast-fed infants 213:230 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 3 18 from accessibility 574:586 arg1 forms 638:642 their pure forms 627:642 their pure forms 627:642 This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. 26613816 1 19 theme different 302:310 arg1 HMOS 312:315 more than 100 different HMOS 288:315 more than 100 different HMOS 288:315 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 1 20 theme HMOS 312:315 arg1 structures 274:283 the structures 270:283 the structures of more than 100 different HMOS 270:315 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 6 21 theme current 1175:1181 arg1 progress 1183:1190 the current progress 1171:1190 the current progress on these aspects 1171:1207 The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. 26613816 0 22 theme Human 0:4 arg1 Oligosaccharides 11:26 Human Milk Oligosaccharides 0:26 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 0:87 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 22 theme Human 0:4 arg1 Synthesis 78:86 Enzyme-Catalyzed Synthesis 61:86 Enzyme-Catalyzed Synthesis 61:86 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 22 theme Human 0:4 arg1 Function 47:54 Function 47:54 Function 47:54 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 22 theme Human 0:4 arg1 HMOS 29:32 HMOS 29:32 HMOS 29:32 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 22 theme Human 0:4 arg1 Structure 36:44 Structure 36:44 Structure 36:44 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 5 23 theme structures 1014:1023 arg1 mixtures 994:1001 mixtures 994:1001 mixtures of defined structures with desired functions 994:1046 This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. 26613816 0 24 theme Milk 6:9 arg1 Oligosaccharides 11:26 Human Milk Oligosaccharides 0:26 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 0:87 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 24 theme Milk 6:9 arg1 Synthesis 78:86 Enzyme-Catalyzed Synthesis 61:86 Enzyme-Catalyzed Synthesis 61:86 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 24 theme Milk 6:9 arg1 Function 47:54 Function 47:54 Function 47:54 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 24 theme Milk 6:9 arg1 HMOS 29:32 HMOS 29:32 HMOS 29:32 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 24 theme Milk 6:9 arg1 Structure 36:44 Structure 36:44 Structure 36:44 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 4 25 from production 761:770 arg1 amounts 814:820 increasing amounts 803:820 increasing amounts 803:820 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 4 26 theme growing 777:783 arg1 number 785:790 a growing number 775:790 a growing number of HMOS 775:798 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 7 27 theme branched 1347:1354 arg1 structures 1356:1365 branched structures 1347:1365 branched structures 1347:1365 Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics. 26613816 4 28 theme increasing 803:812 arg1 amounts 814:820 increasing amounts 803:820 increasing amounts 803:820 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 2 29 theme functions 382:390 arg1 recognition 355:365 the recognition 351:365 the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators 351:463 Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. 26613816 1 30 theme infants 224:230 arg1 health 203:208 the health 199:208 the health of breast-fed infants 199:230 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 7 31 theme complex 1281:1287 arg1 HMOS 1289:1292 more complex HMOS 1276:1292 more complex HMOS 1276:1292 Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics. 26613816 2 32 theme various 374:380 arg1 functions 382:390 the various functions 370:390 the various functions of HMOS 370:398 Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. 26613816 6 33 dep structures 1053:1062 arg1 The 1049:1051 The 1049:1051 The 1049:1051 The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. 26613816 7 34 theme complex 1313:1319 arg1 those 1336:1340 those 1336:1340 those 1336:1340 Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics. 26613816 7 34 theme complex 1313:1319 arg1 HMOS 1321:1324 more complex HMOS 1308:1324 more complex HMOS including those with branched structures 1308:1365 Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics. 26613816 1 35 theme third 159:163 arg1 oligosaccharides 130:145 human milk oligosaccharides 119:145 human milk oligosaccharides (HMOS) 119:152 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 1 35 theme third 159:163 arg1 component 171:179 the third major component 155:179 the third major component of human milk 155:193 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 6 36 theme HMOS 1110:1113 arg1 synthesis 1097:1105 enzyme-catalyzed synthesis 1080:1105 enzyme-catalyzed synthesis 1080:1105 The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. 26613816 6 36 theme HMOS 1110:1113 arg1 functions 1065:1073 functions 1065:1073 functions 1065:1073 The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. 26613816 6 36 theme HMOS 1110:1113 arg1 structures 1053:1062 structures 1053:1062 structures 1053:1062 The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. 26613816 1 37 theme major 165:169 arg1 oligosaccharides 130:145 human milk oligosaccharides 119:145 human milk oligosaccharides (HMOS) 119:152 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 1 37 theme major 165:169 arg1 component 171:179 the third major component 155:179 the third major component of human milk 155:193 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 7 38 theme Future 1210:1215 arg1 efforts 1217:1223 Future efforts 1210:1223 Future efforts 1210:1223 Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics. 26613816 7 39 theme HMOS-inspired 1397:1409 arg1 prebiotics 1411:1420 HMOS-based or HMOS-inspired prebiotics 1383:1420 HMOS-based or HMOS-inspired prebiotics 1383:1420 Future efforts should be devoted to elucidating the structures of more complex HMOS, synthesizing more complex HMOS including those with branched structures, and developing HMOS-based or HMOS-inspired prebiotics, additives, and therapeutics. 26613816 4 40 theme systems 739:745 arg1 development 669:679 the development 665:679 the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems 665:745 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 3 41 theme limited 566:572 arg1 accessibility 574:586 the limited accessibility 562:586 the limited accessibility to large amounts of individual HMOS in their pure forms 562:642 This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. 26613816 5 42 theme roles 892:896 arg1 elucidation 863:873 the elucidation 859:873 the elucidation of the important roles of HMOS 859:904 This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. 26613816 1 43 theme important 93:101 arg1 roles 103:107 The important roles 89:107 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants 89:230 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 2 44 theme HMOS 395:398 arg1 functions 382:390 the various functions 370:390 the various functions of HMOS 370:398 Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. 26613816 2 45 theme species 516:522 arg1 applications 484:495 the applications 480:495 the applications 480:495 Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. 26613816 2 45 theme species 516:522 arg1 clear 533:537 clear 533:537 clear 533:537 Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. 26613816 2 45 theme species 516:522 arg1 roles 470:474 the roles 466:474 the roles 466:474 Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. 26613816 5 46 theme HMOS 953:956 arg1 applications 937:948 the applications 933:948 the applications of HMOS 933:956 This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. 26613816 4 47 from advances 653:660 arg1 development 669:679 the development 665:679 the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems 665:745 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 2 48 theme HMOS 511:514 arg1 species 516:522 individual HMOS species 500:522 individual HMOS species 500:522 Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. 26613816 3 49 theme individual 608:617 arg1 HMOS 619:622 individual HMOS 608:622 individual HMOS 608:622 This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. 26613816 6 50 theme general 1149:1155 arg1 picture 1157:1163 a general picture 1147:1163 a general picture about the current progress on these aspects 1147:1207 The structures, functions, and enzyme-catalyzed synthesis of HMOS are briefly surveyed to provide a general picture about the current progress on these aspects. 26613816 1 51 theme human 184:188 arg1 milk 190:193 human milk 184:193 human milk 184:193 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 2 52 theme individual 500:509 arg1 species 516:522 individual HMOS species 500:522 individual HMOS species 500:522 Despite the recognition of the various functions of HMOS as prebiotics, antiadhesive antimicrobials, and immunomodulators, the roles and the applications of individual HMOS species are less clear. 26613816 3 53 theme large 591:595 arg1 amounts 597:603 large amounts 591:603 large amounts of individual HMOS 591:622 This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. 26613816 3 53 theme large 591:595 arg1 HMOS 619:622 individual HMOS 608:622 individual HMOS 608:622 This is mainly due to the limited accessibility to large amounts of individual HMOS in their pure forms. 26613816 0 54 dep Oligosaccharides 11:26 arg1 Oligosaccharides 11:26 Human Milk Oligosaccharides 0:26 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 0:87 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 54 dep Oligosaccharides 11:26 arg1 Synthesis 78:86 Enzyme-Catalyzed Synthesis 61:86 Enzyme-Catalyzed Synthesis 61:86 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 54 dep Oligosaccharides 11:26 arg1 Function 47:54 Function 47:54 Function 47:54 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 0 54 dep Oligosaccharides 11:26 arg1 Structure 36:44 Structure 36:44 Structure 36:44 Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. 26613816 4 55 theme Current 645:651 arg1 advances 653:660 Current advances 645:660 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems 645:745 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 5 56 theme individual 966:975 arg1 exploration 916:926 exploration 916:926 exploration 916:926 This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. 26613816 5 56 theme individual 966:975 arg1 compounds 977:985 individual compounds 966:985 individual compounds 966:985 This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. 26613816 1 57 theme milk 190:193 arg1 oligosaccharides 130:145 human milk oligosaccharides 119:145 human milk oligosaccharides (HMOS) 119:152 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 1 57 theme milk 190:193 arg1 component 171:179 the third major component 155:179 the third major component of human milk 155:193 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 4 58 theme living-cell 727:737 arg1 systems 739:745 enzymatic, chemoenzymatic, whole-cell, and living-cell systems 684:745 enzymatic, chemoenzymatic, whole-cell, and living-cell systems 684:745 Current advances in the development of enzymatic, chemoenzymatic, whole-cell, and living-cell systems allow for the production of a growing number of HMOS in increasing amounts. 26613816 1 59 theme human 119:123 arg1 component 171:179 the third major component 155:179 the third major component of human milk 155:193 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 1 59 theme human 119:123 arg1 HMOS 148:151 HMOS 148:151 HMOS 148:151 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 1 59 theme human 119:123 arg1 oligosaccharides 130:145 human milk oligosaccharides 119:145 human milk oligosaccharides (HMOS) 119:152 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 5 60 with structures 1014:1023 arg1 functions 1038:1046 desired functions 1030:1046 desired functions 1030:1046 This effort will greatly facilitate the elucidation of the important roles of HMOS and allow exploration into the applications of HMOS both as individual compounds and as mixtures of defined structures with desired functions. 26613816 1 61 theme milk 125:128 arg1 component 171:179 the third major component 155:179 the third major component of human milk 155:193 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 1 61 theme milk 125:128 arg1 HMOS 148:151 HMOS 148:151 HMOS 148:151 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 26613816 1 61 theme milk 125:128 arg1 oligosaccharides 130:145 human milk oligosaccharides 119:145 human milk oligosaccharides (HMOS) 119:152 The important roles played by human milk oligosaccharides (HMOS), the third major component of human milk, in the health of breast-fed infants have been increasingly recognized, as the structures of more than 100 different HMOS have now been elucidated. 1779619 5 0 theme relative 836:843 arg1 sialyloligosaccharides 868:889 the various sialyloligosaccharides 856:889 the various sialyloligosaccharides 856:889 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 0 theme relative 836:843 arg1 amounts 845:851 the relative amounts 832:851 the relative amounts of the various sialyloligosaccharides 832:889 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 1 1 attach isolated 142:149 arg2 carbohydrates 123:135 Sialic acid-containing carbohydrates 100:135 Sialic acid-containing carbohydrates 100:135 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 1 1 attach isolated 142:149 arg1 urine 167:171 sialidosis urine 156:171 sialidosis urine 156:171 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 7 2 theme defective 1264:1272 arg1 catabolism 1274:1283 the defective catabolism 1260:1283 the defective catabolism of glycoproteins in both sialidosis and galactosialidosis 1260:1341 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 7 3 theme beta-galactosidase 1099:1116 arg1 deficiency 1118:1127 the additional beta-galactosidase deficiency 1084:1127 the additional beta-galactosidase deficiency in galactosialidosis 1084:1148 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 5 4 from present 799:805 arg1 urines 815:820 both urines 810:820 both urines 810:820 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 5 theme galactosialidosis 720:736 arg1 urine 738:742 galactosialidosis urine 720:742 galactosialidosis urine 720:742 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 1 6 from combination 178:188 arg1 P-6 219:221 Bio-Gel P-6 and medium-pressure anion-exchange chromatography 211:271 P-6 219:221 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 1 6 from combination 178:188 arg1 chromatography 258:271 Bio-Gel P-6 and medium-pressure anion-exchange chromatography 211:271 chromatography 258:271 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 7 7 theme material 1195:1202 arg1 nature 1172:1177 the nature 1168:1177 the nature of the excreted material 1168:1202 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 6 8 link linked 986:991 arg1 acid 1000:1003 relatively more alpha 2-6 linked sialic acid 960:1003 relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine 960:1054 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 2 9 from analysis 358:365 arg1 Lichrosorb-NH2 390:403 Lichrosorb-NH2 390:403 Lichrosorb-NH2 390:403 The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. 1779619 2 10 theme 500-MHz 323:329 arg1 spectroscopy 338:349 500-MHz 1H-NMR spectroscopy 323:349 500-MHz 1H-NMR spectroscopy 323:349 The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. 1779619 2 11 theme sugar 352:356 arg1 analysis 358:365 sugar analysis 352:365 sugar analysis 352:365 The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. 1779619 2 12 from HPLC 382:385 arg1 Lichrosorb-NH2 390:403 Lichrosorb-NH2 390:403 Lichrosorb-NH2 390:403 The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. 1779619 4 13 theme tri- 649:652 arg1 compounds 674:682 tri- and tetra-antennary compounds 649:682 tri- and tetra-antennary compounds 649:682 Among the structures were fully and partially sialylated mono-, di-, tri- and tetra-antennary compounds. 1779619 4 13 theme tri- 649:652 arg1 mono- 637:641 mono- 637:641 mono- 637:641 Among the structures were fully and partially sialylated mono-, di-, tri- and tetra-antennary compounds. 1779619 6 14 theme sialic 993:998 arg1 acid 1000:1003 relatively more alpha 2-6 linked sialic acid 960:1003 relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine 960:1054 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 3 15 theme sialyloligosaccharides 479:500 arg1 presence 434:441 the presence 430:441 the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types 430:577 These methods indicated the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. 1779619 1 16 theme gel-filtration 193:206 arg1 combination 178:188 a combination 176:188 a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q 176:281 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 5 17 theme sialyloligosaccharides 868:889 arg1 sialyloligosaccharides 868:889 the various sialyloligosaccharides 856:889 the various sialyloligosaccharides 856:889 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 17 theme sialyloligosaccharides 868:889 arg1 amounts 845:851 the relative amounts 832:851 the relative amounts of the various sialyloligosaccharides 832:889 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 6 18 theme linked 986:991 arg1 acid 1000:1003 relatively more alpha 2-6 linked sialic acid 960:1003 relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine 960:1054 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 4 19 theme tetra-antennary 658:672 arg1 compounds 674:682 tri- and tetra-antennary compounds 649:682 tri- and tetra-antennary compounds 649:682 Among the structures were fully and partially sialylated mono-, di-, tri- and tetra-antennary compounds. 1779619 4 19 theme tetra-antennary 658:672 arg1 mono- 637:641 mono- 637:641 mono- 637:641 Among the structures were fully and partially sialylated mono-, di-, tri- and tetra-antennary compounds. 1779619 0 20 theme comparative 2:12 arg1 study 14:18 A comparative study 0:18 A comparative study of sialyloligosaccharides 0:44 A comparative study of sialyloligosaccharides isolated from sialidosis and galactosialidosis urine. 1779619 1 21 theme Sialic 100:105 arg1 carbohydrates 123:135 Sialic acid-containing carbohydrates 100:135 Sialic acid-containing carbohydrates 100:135 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 5 22 attach present 799:805 arg2 present 799:805 present 799:805 present 799:805 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 22 attach present 799:805 arg2 carbohydrates 780:792 essentially the same carbohydrates 759:792 essentially the same carbohydrates 759:792 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 22 attach present 799:805 arg1 urines 815:820 both urines 810:820 both urines 810:820 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 1 23 theme Bio-Gel 211:217 arg1 P-6 219:221 Bio-Gel P-6 and medium-pressure anion-exchange chromatography 211:271 P-6 219:221 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 7 24 theme sialidase 1217:1225 arg1 deficiency 1227:1236 the sialidase deficiency 1213:1236 the sialidase deficiency 1213:1236 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 1 25 theme acid-containing 107:121 arg1 carbohydrates 123:135 Sialic acid-containing carbohydrates 100:135 Sialic acid-containing carbohydrates 100:135 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 3 26 theme branching 531:539 arg1 pattern 541:547 branching pattern 531:547 branching pattern 531:547 These methods indicated the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. 1779619 6 27 theme alpha 976:980 arg1 acid 1000:1003 relatively more alpha 2-6 linked sialic acid 960:1003 relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine 960:1054 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 2 28 theme 1H-NMR 331:336 arg1 spectroscopy 338:349 500-MHz 1H-NMR spectroscopy 323:349 500-MHz 1H-NMR spectroscopy 323:349 The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. 1779619 1 29 theme medium-pressure 227:241 arg1 chromatography 258:271 Bio-Gel P-6 and medium-pressure anion-exchange chromatography 211:271 chromatography 258:271 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 3 30 theme N-acetyllactosamine 454:472 arg1 sialyloligosaccharides 479:500 various N-acetyllactosamine type sialyloligosaccharides 446:500 various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types 446:577 These methods indicated the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. 1779619 3 31 theme linkage 565:571 arg1 types 573:577 linkage types 565:577 linkage types 565:577 These methods indicated the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. 1779619 7 32 theme excreted 1186:1193 arg1 material 1195:1202 the excreted material 1182:1202 the excreted material 1182:1202 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 6 33 theme more 971:974 arg1 acid 1000:1003 relatively more alpha 2-6 linked sialic acid 960:1003 relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine 960:1054 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 0 34 dep sialidosis 60:69 arg1 urine 93:97 urine 93:97 urine 93:97 A comparative study of sialyloligosaccharides isolated from sialidosis and galactosialidosis urine. 1779619 1 35 theme anion-exchange 243:256 arg1 chromatography 258:271 Bio-Gel P-6 and medium-pressure anion-exchange chromatography 211:271 chromatography 258:271 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 0 36 theme sialyloligosaccharides 23:44 arg1 study 14:18 A comparative study 0:18 A comparative study of sialyloligosaccharides 0:44 A comparative study of sialyloligosaccharides isolated from sialidosis and galactosialidosis urine. 1779619 5 37 from urine 738:742 arg1 results 707:713 the results 703:713 the results from galactosialidosis urine 703:742 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 3 38 theme type 474:477 arg1 sialyloligosaccharides 479:500 various N-acetyllactosamine type sialyloligosaccharides 446:500 various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types 446:577 These methods indicated the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. 1779619 5 39 located present 799:805 arg2 present 799:805 present 799:805 present 799:805 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 39 located present 799:805 arg1 urines 815:820 both urines 810:820 both urines 810:820 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 39 located present 799:805 arg2 carbohydrates 780:792 essentially the same carbohydrates 759:792 essentially the same carbohydrates 759:792 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 40 theme various 860:866 arg1 sialyloligosaccharides 868:889 the various sialyloligosaccharides 856:889 the various sialyloligosaccharides 856:889 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 41 from urines 815:820 arg1 present 799:805 present 799:805 present 799:805 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 41 from urines 815:820 arg1 carbohydrates 780:792 essentially the same carbohydrates 759:792 essentially the same carbohydrates 759:792 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 7 42 gly glycoproteins 1288:1300 arg1 glycoproteins 1288:1300 glycoproteins 1288:1300 glycoproteins 1288:1300 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 1 43 from chromatography 258:271 arg1 Q 281:281 Mono Q 276:281 Mono Q 276:281 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 1 43 from chromatography 258:271 arg1 combination 178:188 a combination 176:188 a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q 176:281 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 6 44 contain contained 950:958 arg1 oligosaccharides 933:948 Sialidosis urinary oligosaccharides 914:948 Sialidosis urinary oligosaccharides 914:948 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 6 44 contain contained 950:958 arg2 acid 1000:1003 relatively more alpha 2-6 linked sialic acid 960:1003 relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine 960:1054 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 3 45 theme various 446:452 arg1 sialyloligosaccharides 479:500 various N-acetyllactosamine type sialyloligosaccharides 446:500 various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types 446:577 These methods indicated the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. 1779619 6 46 from urine 1050:1054 arg1 oligosaccharides 1010:1025 oligosaccharides 1010:1025 oligosaccharides from galactosialidosis urine 1010:1054 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 6 47 theme urinary 925:931 arg1 oligosaccharides 933:948 Sialidosis urinary oligosaccharides 914:948 Sialidosis urinary oligosaccharides 914:948 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 2 48 theme analytical 371:380 arg1 HPLC 382:385 analytical HPLC 371:385 analytical HPLC 371:385 The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. 1779619 7 49 from catabolism 1274:1283 arg1 galactosialidosis 1325:1341 galactosialidosis 1325:1341 galactosialidosis 1325:1341 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 7 49 from catabolism 1274:1283 arg1 sialidosis 1310:1319 sialidosis 1310:1319 sialidosis 1310:1319 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 5 50 with comparison 687:696 arg1 results 707:713 the results 703:713 the results from galactosialidosis urine 703:742 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 7 51 theme glycoproteins 1288:1300 arg1 catabolism 1274:1283 the defective catabolism 1260:1283 the defective catabolism of glycoproteins in both sialidosis and galactosialidosis 1260:1341 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 1 52 theme sialidosis 156:165 arg1 urine 167:171 sialidosis urine 156:171 sialidosis urine 156:171 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 7 53 theme additional 1088:1097 arg1 deficiency 1118:1127 the additional beta-galactosidase deficiency 1084:1127 the additional beta-galactosidase deficiency in galactosialidosis 1084:1148 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 5 54 theme same 775:778 arg1 present 799:805 present 799:805 present 799:805 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 5 54 theme same 775:778 arg1 carbohydrates 780:792 essentially the same carbohydrates 759:792 essentially the same carbohydrates 759:792 A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. 1779619 6 55 theme Sialidosis 914:923 arg1 oligosaccharides 933:948 Sialidosis urinary oligosaccharides 914:948 Sialidosis urinary oligosaccharides 914:948 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 2 56 theme Q 293:293 arg1 fractions 295:303 The Mono Q fractions 284:303 The Mono Q fractions 284:303 The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. 1779619 3 57 theme sialic 553:558 arg1 acid 560:563 sialic acid 553:563 sialic acid 553:563 These methods indicated the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. 1779619 1 58 theme Mono 276:279 arg1 Q 281:281 Mono Q 276:281 Mono Q 276:281 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 2 59 theme Mono 288:291 arg1 fractions 295:303 The Mono Q fractions 284:303 The Mono Q fractions 284:303 The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. 1779619 1 60 from P-6 219:221 arg1 Q 281:281 Mono Q 276:281 Mono Q 276:281 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 1 60 from P-6 219:221 arg1 combination 178:188 a combination 176:188 a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q 176:281 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 7 61 from deficiency 1118:1127 arg1 galactosialidosis 1132:1148 galactosialidosis 1132:1148 galactosialidosis 1132:1148 It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis. 1779619 6 62 theme galactosialidosis 1032:1048 arg1 urine 1050:1054 galactosialidosis urine 1032:1054 galactosialidosis urine 1032:1054 Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. 1779619 3 63 dep pattern 541:547 arg1 types 573:577 linkage types 565:577 linkage types 565:577 These methods indicated the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. 1779619 1 64 from gel-filtration 193:206 arg1 P-6 219:221 Bio-Gel P-6 and medium-pressure anion-exchange chromatography 211:271 P-6 219:221 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 1 64 from gel-filtration 193:206 arg1 chromatography 258:271 Bio-Gel P-6 and medium-pressure anion-exchange chromatography 211:271 chromatography 258:271 Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. 1779619 2 65 from spectroscopy 338:349 arg1 Lichrosorb-NH2 390:403 Lichrosorb-NH2 390:403 Lichrosorb-NH2 390:403 The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. 3997819 13 0 theme branched-chain 1795:1808 arg1 compounds 1810:1818 the branched-chain compounds 1791:1818 the branched-chain compounds 1791:1818 The proposed structures for the branched-chain compounds are as follows. 3997819 7 1 theme visceral 1236:1243 arg1 tissues 1245:1251 visceral tissues 1236:1251 visceral tissues 1236:1251 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 5 2 theme human 995:999 arg1 tissues 1001:1007 human tissues 995:1007 human tissues 995:1007 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 8 3 dep S 1428:1428 arg1 Biol 1441:1444 Biol 1441:1444 Biol 1441:1444 These results suggest that the biosynthetic enzymes, GlcNAc transferase III (Narasimham, S. (1982) J. Biol. 3997819 0 4 theme disease 111:117 arg1 tissue 119:124 Sandhoff disease tissue 102:124 Sandhoff disease tissue 102:124 Characterization and analysis of branched-chain N-acetylglucosaminyl oligosaccharides accumulating in Sandhoff disease tissue. 3997819 12 5 contain have 1608:1611 arg1 258 1534:1536 258 1534:1536 258 1534:1536 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 12 5 contain have 1608:1611 arg2 distribution 1627:1638 a generalized distribution 1613:1638 a generalized distribution 1613:1638 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 7 6 from levels 1322:1327 arg1 brain 1332:1336 brain 1332:1336 brain 1332:1336 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 1 7 theme abundant 211:218 arg1 Evidence 127:134 Evidence 127:134 Evidence that biantennary bisected oligosaccharide side chains of glycoproteins 127:205 Evidence that biantennary bisected oligosaccharide side chains of glycoproteins are abundant substrates for lysosomes. 3997819 1 7 theme abundant 211:218 arg1 substrates 220:229 abundant substrates 211:229 abundant substrates for lysosomes 211:243 Evidence that biantennary bisected oligosaccharide side chains of glycoproteins are abundant substrates for lysosomes. 3997819 10 8 dep Biol 1522:1525 arg1 257 1453:1455 257 1453:1455 257 1453:1455 257, 10235-10242) and IV (Gleeson, P.A., and Schachter, H. (1983) J. Biol. 3997819 10 8 dep Biol 1522:1525 arg1 P.A. 1488:1491 P.A. 1488:1491 P.A. 1488:1491 257, 10235-10242) and IV (Gleeson, P.A., and Schachter, H. (1983) J. Biol. 3997819 10 8 dep Biol 1522:1525 arg1 Schachter 1498:1506 Schachter 1498:1506 Schachter 1498:1506 257, 10235-10242) and IV (Gleeson, P.A., and Schachter, H. (1983) J. Biol. 3997819 10 8 dep Biol 1522:1525 arg1 Gleeson 1479:1485 Gleeson 1479:1485 Gleeson 1479:1485 257, 10235-10242) and IV (Gleeson, P.A., and Schachter, H. (1983) J. Biol. 3997819 10 8 dep Biol 1522:1525 arg1 IV 1475:1476 IV 1475:1476 IV 1475:1476 257, 10235-10242) and IV (Gleeson, P.A., and Schachter, H. (1983) J. Biol. 3997819 3 9 theme Detailed 456:463 arg1 analysis 476:483 Detailed structural analysis 456:483 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, 456:551 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, was carried out using 360 MHz proton magnetic resonance spectroscopy. 3997819 10 10 dep Gleeson 1479:1485 arg1 1983 1513:1516 1983 1513:1516 1983 1513:1516 257, 10235-10242) and IV (Gleeson, P.A., and Schachter, H. (1983) J. Biol. 3997819 10 11 dep 257 1453:1455 arg1 10235-10242 1458:1468 10235-10242 1458:1468 10235-10242 1458:1468 257, 10235-10242) and IV (Gleeson, P.A., and Schachter, H. (1983) J. Biol. 3997819 3 12 theme structural 465:474 arg1 analysis 476:483 Detailed structural analysis 456:483 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, 456:551 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, was carried out using 360 MHz proton magnetic resonance spectroscopy. 3997819 13 13 theme proposed 1767:1774 arg1 structures 1776:1785 The proposed structures 1763:1785 The proposed structures for the branched-chain compounds 1763:1818 The proposed structures for the branched-chain compounds are as follows. 3997819 12 14 from levels 1653:1658 arg1 viscera 1683:1689 human viscera 1677:1689 human viscera 1677:1689 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 5 15 from lysosomes 982:990 arg1 tissues 1001:1007 human tissues 995:1007 human tissues 995:1007 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 2 16 theme Sandhoff 364:371 arg1 disease 373:379 Sandhoff disease 364:379 Sandhoff disease 364:379 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 12 17 theme varying 1645:1651 arg1 levels 1653:1658 varying levels 1645:1658 varying levels of expression in human viscera 1645:1689 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 8 18 theme GlcNAc 1392:1397 arg1 enzymes 1383:1389 the biosynthetic enzymes 1366:1389 the biosynthetic enzymes 1366:1389 These results suggest that the biosynthetic enzymes, GlcNAc transferase III (Narasimham, S. (1982) J. Biol. 3997819 8 18 theme GlcNAc 1392:1397 arg1 transferase 1399:1409 GlcNAc transferase III 1392:1413 GlcNAc transferase III (Narasimham, S. (1982) J. Biol 1392:1444 These results suggest that the biosynthetic enzymes, GlcNAc transferase III (Narasimham, S. (1982) J. Biol. 3997819 12 19 theme human 1677:1681 arg1 viscera 1683:1689 human viscera 1677:1689 human viscera 1677:1689 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 1 20 theme bisected 153:160 arg1 chains 183:188 bisected oligosaccharide side chains 153:188 bisected oligosaccharide side chains of glycoproteins 153:205 Evidence that biantennary bisected oligosaccharide side chains of glycoproteins are abundant substrates for lysosomes. 3997819 7 21 theme storage 1274:1280 arg1 product 1282:1288 the major storage product 1264:1288 the major storage product 1264:1288 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 7 21 theme storage 1274:1280 arg1 it 1257:1258 it 1257:1258 it 1257:1258 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 5 22 theme oligosaccharide 926:940 arg1 chains 947:952 biantennary bisected oligosaccharide side chains 905:952 biantennary bisected oligosaccharide side chains 905:952 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 3 23 theme resonance 599:607 arg1 spectroscopy 609:620 360 MHz proton magnetic resonance spectroscopy 575:620 360 MHz proton magnetic resonance spectroscopy 575:620 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, was carried out using 360 MHz proton magnetic resonance spectroscopy. 3997819 4 24 theme oligosaccharides 749:764 arg1 component 725:733 a major component 717:733 a major component of the stored oligosaccharides 717:764 The biantennary bisected heptasaccharide, oligosaccharide 6, was ubiquitously distributed and a major component of the stored oligosaccharides in all tissues analyzed including, liver, spleen, kidney, lung, pancreas, and brain. 3997819 3 25 theme abundant 503:510 arg1 oligosaccharides 523:538 oligosaccharides 4, 5, and 6 523:550 oligosaccharides 4, 5, and 6 523:550 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, was carried out using 360 MHz proton magnetic resonance spectroscopy. 3997819 3 25 theme abundant 503:510 arg1 fractions 512:520 the three most abundant fractions 488:520 the three most abundant fractions 488:520 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, was carried out using 360 MHz proton magnetic resonance spectroscopy. 3997819 7 26 from product 1282:1288 arg1 pancreas 1293:1300 pancreas 1293:1300 pancreas 1293:1300 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 3 27 theme fractions 512:520 arg1 analysis 476:483 Detailed structural analysis 456:483 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, 456:551 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, was carried out using 360 MHz proton magnetic resonance spectroscopy. 3997819 2 28 theme patients 350:357 arg1 tissues 335:341 visceral and neural tissues 315:341 visceral and neural tissues of two patients with Sandhoff disease 315:379 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 4 29 theme stored 742:747 arg1 oligosaccharides 749:764 the stored oligosaccharides 738:764 the stored oligosaccharides 738:764 The biantennary bisected heptasaccharide, oligosaccharide 6, was ubiquitously distributed and a major component of the stored oligosaccharides in all tissues analyzed including, liver, spleen, kidney, lung, pancreas, and brain. 3997819 12 30 theme structures 1596:1605 arg1 synthesis 1577:1585 synthesis 1577:1585 synthesis of these structures 1577:1605 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 6 31 theme storage 1058:1064 arg1 product 1066:1072 the predominant storage product 1042:1072 the predominant storage product 1042:1072 Moreover, oligosaccharide 6 was the predominant storage product in brain comprising 70% of the total accumulating water-soluble glycoconjugates. 3997819 6 31 theme storage 1058:1064 arg1 oligosaccharide 1020:1034 oligosaccharide 6 1020:1036 oligosaccharide 6 1020:1036 Moreover, oligosaccharide 6 was the predominant storage product in brain comprising 70% of the total accumulating water-soluble glycoconjugates. 3997819 7 32 theme low 1318:1320 arg1 levels 1322:1327 very low levels 1313:1327 very low levels 1313:1327 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 12 33 from viscera 1683:1689 arg1 levels 1653:1658 varying levels 1645:1658 varying levels of expression in human viscera 1645:1689 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 2 34 with patients 350:357 arg1 disease 373:379 Sandhoff disease 364:379 Sandhoff disease 364:379 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 7 35 theme major 1268:1272 arg1 product 1282:1288 the major storage product 1264:1288 the major storage product 1264:1288 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 7 35 theme major 1268:1272 arg1 it 1257:1258 it 1257:1258 it 1257:1258 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 6 36 from product 1066:1072 arg1 brain 1077:1081 brain 1077:1081 brain comprising 70% of the total accumulating water-soluble glycoconjugates 1077:1152 Moreover, oligosaccharide 6 was the predominant storage product in brain comprising 70% of the total accumulating water-soluble glycoconjugates. 3997819 12 37 theme neural 1748:1753 arg1 tissue 1755:1760 neural tissue 1748:1760 neural tissue 1748:1760 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 5 38 theme bisected 917:924 arg1 chains 947:952 biantennary bisected oligosaccharide side chains 905:952 biantennary bisected oligosaccharide side chains 905:952 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 5 39 theme biantennary 905:915 arg1 chains 947:952 biantennary bisected oligosaccharide side chains 905:952 biantennary bisected oligosaccharide side chains 905:952 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 3 40 theme MHz 579:581 arg1 resonance 599:607 360 MHz proton magnetic resonance 575:607 360 MHz proton magnetic resonance spectroscopy 575:620 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, was carried out using 360 MHz proton magnetic resonance spectroscopy. 3997819 4 41 theme major 719:723 arg1 component 725:733 a major component 717:733 a major component of the stored oligosaccharides 717:764 The biantennary bisected heptasaccharide, oligosaccharide 6, was ubiquitously distributed and a major component of the stored oligosaccharides in all tissues analyzed including, liver, spleen, kidney, lung, pancreas, and brain. 3997819 0 42 theme N-acetylglucosaminyl 48:67 arg1 oligosaccharides 69:84 branched-chain N-acetylglucosaminyl oligosaccharides 33:84 branched-chain N-acetylglucosaminyl oligosaccharides 33:84 Characterization and analysis of branched-chain N-acetylglucosaminyl oligosaccharides accumulating in Sandhoff disease tissue. 3997819 2 43 theme performance 421:431 arg1 chromatography 440:453 high performance liquid chromatography 416:453 high performance liquid chromatography 416:453 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 5 44 contain containing 894:903 arg1 substrates 967:976 abundant substrates 958:976 abundant substrates for lysosomes in human tissues 958:1007 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 5 44 contain containing 894:903 arg1 glycoproteins 880:892 glycoproteins 880:892 glycoproteins containing biantennary bisected oligosaccharide side chains 880:952 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 5 44 contain containing 894:903 arg2 chains 947:952 biantennary bisected oligosaccharide side chains 905:952 biantennary bisected oligosaccharide side chains 905:952 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 5 45 gly glycoproteins 880:892 arg1 glycoproteins 880:892 glycoproteins 880:892 glycoproteins containing biantennary bisected oligosaccharide side chains 880:952 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 5 45 gly glycoproteins 880:892 arg1 substrates 967:976 abundant substrates 958:976 abundant substrates for lysosomes in human tissues 958:1007 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 12 46 theme generalized 1615:1625 arg1 distribution 1627:1638 a generalized distribution 1613:1638 a generalized distribution 1613:1638 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 5 47 theme side 942:945 arg1 chains 947:952 biantennary bisected oligosaccharide side chains 905:952 biantennary bisected oligosaccharide side chains 905:952 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 0 48 theme branched-chain 33:46 arg1 oligosaccharides 69:84 branched-chain N-acetylglucosaminyl oligosaccharides 33:84 branched-chain N-acetylglucosaminyl oligosaccharides 33:84 Characterization and analysis of branched-chain N-acetylglucosaminyl oligosaccharides accumulating in Sandhoff disease tissue. 3997819 6 49 theme predominant 1046:1056 arg1 product 1066:1072 the predominant storage product 1042:1072 the predominant storage product 1042:1072 Moreover, oligosaccharide 6 was the predominant storage product in brain comprising 70% of the total accumulating water-soluble glycoconjugates. 3997819 6 49 theme predominant 1046:1056 arg1 oligosaccharide 1020:1034 oligosaccharide 6 1020:1036 oligosaccharide 6 1020:1036 Moreover, oligosaccharide 6 was the predominant storage product in brain comprising 70% of the total accumulating water-soluble glycoconjugates. 3997819 8 50 theme biosynthetic 1370:1381 arg1 enzymes 1383:1389 the biosynthetic enzymes 1366:1389 the biosynthetic enzymes 1366:1389 These results suggest that the biosynthetic enzymes, GlcNAc transferase III (Narasimham, S. (1982) J. Biol. 3997819 8 50 theme biosynthetic 1370:1381 arg1 transferase 1399:1409 GlcNAc transferase III 1392:1413 GlcNAc transferase III (Narasimham, S. (1982) J. Biol 1392:1444 These results suggest that the biosynthetic enzymes, GlcNAc transferase III (Narasimham, S. (1982) J. Biol. 3997819 2 51 theme visceral 315:322 arg1 tissues 335:341 visceral and neural tissues 315:341 visceral and neural tissues of two patients with Sandhoff disease 315:379 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 6 52 theme glycoconjugates 1138:1152 arg1 % 1096:1096 70% 1094:1096 70% of the total accumulating water-soluble glycoconjugates 1094:1152 Moreover, oligosaccharide 6 was the predominant storage product in brain comprising 70% of the total accumulating water-soluble glycoconjugates. 3997819 6 52 theme glycoconjugates 1138:1152 arg1 glycoconjugates 1138:1152 the total accumulating water-soluble glycoconjugates 1101:1152 the total accumulating water-soluble glycoconjugates 1101:1152 Moreover, oligosaccharide 6 was the predominant storage product in brain comprising 70% of the total accumulating water-soluble glycoconjugates. 3997819 1 53 gly glycoproteins 193:205 arg1 glycoproteins 193:205 glycoproteins 193:205 glycoproteins 193:205 Evidence that biantennary bisected oligosaccharide side chains of glycoproteins are abundant substrates for lysosomes. 3997819 2 54 theme liquid 433:438 arg1 chromatography 440:453 high performance liquid chromatography 416:453 high performance liquid chromatography 416:453 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 0 55 theme oligosaccharides 69:84 arg1 analysis 21:28 analysis 21:28 analysis 21:28 Characterization and analysis of branched-chain N-acetylglucosaminyl oligosaccharides accumulating in Sandhoff disease tissue. 3997819 0 55 theme oligosaccharides 69:84 arg1 Characterization 0:15 Characterization 0:15 Characterization 0:15 Characterization and analysis of branched-chain N-acetylglucosaminyl oligosaccharides accumulating in Sandhoff disease tissue. 3997819 12 56 from expression 1734:1743 arg1 tissue 1755:1760 neural tissue 1748:1760 neural tissue 1748:1760 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 7 57 theme similar 1212:1218 arg1 distribution 1220:1231 a similar distribution 1210:1231 a similar distribution 1210:1231 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 1 58 theme oligosaccharide 162:176 arg1 chains 183:188 bisected oligosaccharide side chains 153:188 bisected oligosaccharide side chains of glycoproteins 153:205 Evidence that biantennary bisected oligosaccharide side chains of glycoproteins are abundant substrates for lysosomes. 3997819 7 59 contain had 1206:1208 arg1 Oligosaccharide 1155:1169 Oligosaccharide 5 1155:1171 Oligosaccharide 5 1155:1171 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 7 59 contain had 1206:1208 arg2 distribution 1220:1231 a similar distribution 1210:1231 a similar distribution 1210:1231 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 7 59 contain had 1206:1208 arg1 heptasaccharide 1189:1203 heptasaccharide 1189:1203 heptasaccharide 1189:1203 Oligosaccharide 5, a triantennary heptasaccharide, had a similar distribution in visceral tissues and it was the major storage product in pancreas but was at very low levels in brain. 3997819 12 60 from expression 1663:1672 arg1 viscera 1683:1689 human viscera 1677:1689 human viscera 1677:1689 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 2 61 theme N-acetylglucosaminyl 261:280 arg1 oligosaccharides 282:297 Branched chain N-acetylglucosaminyl oligosaccharides 246:297 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease 246:379 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 8 62 dep transferase 1399:1409 arg1 S 1428:1428 S 1428:1428 S 1428:1428 These results suggest that the biosynthetic enzymes, GlcNAc transferase III (Narasimham, S. (1982) J. Biol. 3997819 8 62 dep transferase 1399:1409 arg1 1982 1432:1435 1982 1432:1435 1982 1432:1435 These results suggest that the biosynthetic enzymes, GlcNAc transferase III (Narasimham, S. (1982) J. Biol. 3997819 6 63 theme accumulating 1111:1122 arg1 glycoconjugates 1138:1152 the total accumulating water-soluble glycoconjugates 1101:1152 the total accumulating water-soluble glycoconjugates 1101:1152 Moreover, oligosaccharide 6 was the predominant storage product in brain comprising 70% of the total accumulating water-soluble glycoconjugates. 3997819 1 64 theme side 178:181 arg1 chains 183:188 bisected oligosaccharide side chains 153:188 bisected oligosaccharide side chains of glycoproteins 153:205 Evidence that biantennary bisected oligosaccharide side chains of glycoproteins are abundant substrates for lysosomes. 3997819 6 65 theme water-soluble 1124:1136 arg1 glycoconjugates 1138:1152 the total accumulating water-soluble glycoconjugates 1101:1152 the total accumulating water-soluble glycoconjugates 1101:1152 Moreover, oligosaccharide 6 was the predominant storage product in brain comprising 70% of the total accumulating water-soluble glycoconjugates. 3997819 8 66 dep suggest 1353:1359 arg1 enzymes 1383:1389 the biosynthetic enzymes 1366:1389 the biosynthetic enzymes 1366:1389 These results suggest that the biosynthetic enzymes, GlcNAc transferase III (Narasimham, S. (1982) J. Biol. 3997819 8 66 dep suggest 1353:1359 arg1 transferase 1399:1409 GlcNAc transferase III 1392:1413 GlcNAc transferase III (Narasimham, S. (1982) J. Biol 1392:1444 These results suggest that the biosynthetic enzymes, GlcNAc transferase III (Narasimham, S. (1982) J. Biol. 3997819 2 67 theme chain 255:259 arg1 oligosaccharides 282:297 Branched chain N-acetylglucosaminyl oligosaccharides 246:297 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease 246:379 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 12 68 dep 258 1534:1536 arg1 6162-6173 1539:1547 6162-6173 1539:1547 6162-6173 1539:1547 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 3 69 theme magnetic 590:597 arg1 resonance 599:607 360 MHz proton magnetic resonance 575:607 360 MHz proton magnetic resonance spectroscopy 575:620 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, was carried out using 360 MHz proton magnetic resonance spectroscopy. 3997819 12 70 theme transferase 1702:1712 arg1 IV 1714:1715 transferase IV 1702:1715 transferase IV 1702:1715 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 3997819 2 71 theme high 416:419 arg1 chromatography 440:453 high performance liquid chromatography 416:453 high performance liquid chromatography 416:453 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 0 72 theme Sandhoff 102:109 arg1 tissue 119:124 Sandhoff disease tissue 102:124 Sandhoff disease tissue 102:124 Characterization and analysis of branched-chain N-acetylglucosaminyl oligosaccharides accumulating in Sandhoff disease tissue. 3997819 2 73 theme Branched 246:253 arg1 oligosaccharides 282:297 Branched chain N-acetylglucosaminyl oligosaccharides 246:297 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease 246:379 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 3 74 theme proton 583:588 arg1 resonance 599:607 360 MHz proton magnetic resonance 575:607 360 MHz proton magnetic resonance spectroscopy 575:620 Detailed structural analysis of the three most abundant fractions, oligosaccharides 4, 5, and 6, was carried out using 360 MHz proton magnetic resonance spectroscopy. 3997819 5 75 theme abundant 958:965 arg1 glycoproteins 880:892 glycoproteins 880:892 glycoproteins containing biantennary bisected oligosaccharide side chains 880:952 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 5 75 theme abundant 958:965 arg1 substrates 967:976 abundant substrates 958:976 abundant substrates for lysosomes in human tissues 958:1007 This analysis indicates that glycoproteins containing biantennary bisected oligosaccharide side chains are abundant substrates for lysosomes in human tissues. 3997819 6 76 theme total 1105:1109 arg1 glycoconjugates 1138:1152 the total accumulating water-soluble glycoconjugates 1101:1152 the total accumulating water-soluble glycoconjugates 1101:1152 Moreover, oligosaccharide 6 was the predominant storage product in brain comprising 70% of the total accumulating water-soluble glycoconjugates. 3997819 2 77 theme neural 328:333 arg1 tissues 335:341 visceral and neural tissues 315:341 visceral and neural tissues of two patients with Sandhoff disease 315:379 Branched chain N-acetylglucosaminyl oligosaccharides accumulating in visceral and neural tissues of two patients with Sandhoff disease were isolated and quantified using high performance liquid chromatography. 3997819 1 78 theme glycoproteins 193:205 arg1 chains 183:188 bisected oligosaccharide side chains 153:188 bisected oligosaccharide side chains of glycoproteins 153:205 Evidence that biantennary bisected oligosaccharide side chains of glycoproteins are abundant substrates for lysosomes. 3997819 12 79 theme expression 1663:1672 arg1 levels 1653:1658 varying levels 1645:1658 varying levels of expression in human viscera 1645:1689 258, 6162-6173), which are responsible for synthesis of these structures, have a generalized distribution with varying levels of expression in human viscera, moreover, transferase IV may have limited expression in neural tissue. 2246252 0 0 theme patients 95:102 arg1 urine 86:90 urine 86:90 urine of patients with beta-mannosidosis 86:125 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine, a novel compound occurring in urine of patients with beta-mannosidosis. 2246252 3 1 theme 2-6Man 743:748 arg1 beta 750:753 NeuAc alpha 2-6Man beta 731:753 NeuAc alpha 2-6Man beta 1-4GlcNAc 731:763 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 1 2 theme permeation 182:191 arg1 chromatography 193:206 gel permeation chromatography 178:206 gel permeation chromatography on Bio-Gel P-2 178:221 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 2246252 4 3 theme linear 771:776 arg1 trisaccharide 778:790 This linear trisaccharide 766:790 This linear trisaccharide 766:790 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 4 3 theme linear 771:776 arg1 result 817:822 the result 813:822 the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc 813:905 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 0 4 with patients 95:102 arg1 beta-mannosidosis 109:125 beta-mannosidosis 109:125 beta-mannosidosis 109:125 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine, a novel compound occurring in urine of patients with beta-mannosidosis. 2246252 3 5 theme reduced 526:532 arg1 analogue 534:541 its reduced analogue 522:541 its reduced analogue 522:541 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 3 6 theme Structural 464:473 arg1 characterization 475:490 Structural characterization 464:490 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy 464:671 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 3 7 theme NeuAc 731:735 arg1 beta 750:753 NeuAc alpha 2-6Man beta 731:753 NeuAc alpha 2-6Man beta 1-4GlcNAc 731:763 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 1 8 from chromatography 193:206 arg1 P-2 219:221 Bio-Gel P-2 211:221 Bio-Gel P-2 211:221 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 2246252 4 9 theme accumulating 865:876 arg1 compound 878:885 the major accumulating compound 855:885 the major accumulating compound 855:885 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 4 9 theme accumulating 865:876 arg1 1-4GlcNAc 897:905 Man beta 1-4GlcNAc 888:905 Man beta 1-4GlcNAc 888:905 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 2 10 dep detected 395:402 arg1 compared 424:431 compared 424:431 compared to that of Man beta 1-4GlcNAc 424:461 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 5 11 theme sialidase 1000:1008 arg1 digestion 1010:1018 sialidase digestion 1000:1018 sialidase digestion 1000:1018 The hitherto unknown linkage between sialic acid and mannose was shown to be susceptible to sialidase digestion. 2246252 2 12 theme beta 318:321 arg1 1-4GlcNAc 323:331 the disaccharide Man beta 1-4GlcNAc 297:331 the disaccharide Man beta 1-4GlcNAc as the major component 297:354 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 2 13 theme acid-containing 366:380 arg1 compound 382:389 a sialic acid-containing compound 357:389 a sialic acid-containing compound 357:389 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 2 14 theme Man 314:316 arg1 1-4GlcNAc 323:331 the disaccharide Man beta 1-4GlcNAc 297:331 the disaccharide Man beta 1-4GlcNAc as the major component 297:354 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 3 15 theme beta 750:753 arg1 1-4GlcNAc 755:763 NeuAc alpha 2-6Man beta 1-4GlcNAc 731:763 NeuAc alpha 2-6Man beta 1-4GlcNAc 731:763 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 4 16 theme compound 878:885 arg1 2-6-sialylation 836:850 an alpha 2-6-sialylation 827:850 an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc 827:905 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 0 17 theme Sialyl-alpha 0:11 arg1 1-4-N-acetylglucosamine 31:53 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine 0:53 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine 0:53 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine, a novel compound occurring in urine of patients with beta-mannosidosis. 2246252 0 17 theme Sialyl-alpha 0:11 arg1 compound 64:71 a novel compound 56:71 a novel compound 56:71 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine, a novel compound occurring in urine of patients with beta-mannosidosis. 2246252 1 18 theme Bio-Gel 211:217 arg1 P-2 219:221 Bio-Gel P-2 211:221 Bio-Gel P-2 211:221 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 2246252 0 19 theme 2-6-mannosyl-beta 13:29 arg1 1-4-N-acetylglucosamine 31:53 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine 0:53 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine 0:53 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine, a novel compound occurring in urine of patients with beta-mannosidosis. 2246252 0 19 theme 2-6-mannosyl-beta 13:29 arg1 compound 64:71 a novel compound 56:71 a novel compound 56:71 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine, a novel compound occurring in urine of patients with beta-mannosidosis. 2246252 4 20 theme beta 892:895 arg1 compound 878:885 the major accumulating compound 855:885 the major accumulating compound 855:885 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 4 20 theme beta 892:895 arg1 1-4GlcNAc 897:905 Man beta 1-4GlcNAc 888:905 Man beta 1-4GlcNAc 888:905 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 2 21 theme beta 448:451 arg1 1-4GlcNAc 453:461 Man beta 1-4GlcNAc 444:461 Man beta 1-4GlcNAc 444:461 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 3 22 theme novel 704:708 arg1 constituent 718:728 a novel urinary constituent 702:728 a novel urinary constituent 702:728 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 2 23 theme major 340:344 arg1 component 346:354 the major component 336:354 the major component 336:354 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 5 24 theme sialic 945:950 arg1 acid 952:955 sialic acid 945:955 sialic acid 945:955 The hitherto unknown linkage between sialic acid and mannose was shown to be susceptible to sialidase digestion. 2246252 2 25 theme Man 444:446 arg1 1-4GlcNAc 453:461 Man beta 1-4GlcNAc 444:461 Man beta 1-4GlcNAc 444:461 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 4 26 theme 2-6-sialylation 836:850 arg1 trisaccharide 778:790 This linear trisaccharide 766:790 This linear trisaccharide 766:790 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 4 26 theme 2-6-sialylation 836:850 arg1 result 817:822 the result 813:822 the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc 813:905 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 3 27 theme methylation 574:584 arg1 analysis 586:593 methylation analysis 574:593 methylation analysis 574:593 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 3 28 theme gas-liquid 596:605 arg1 spectrometry 627:638 gas-liquid chromatography-mass spectrometry 596:638 gas-liquid chromatography-mass spectrometry 596:638 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 3 29 theme sugar 546:550 arg1 analysis 564:571 sugar composition analysis 546:571 sugar composition analysis 546:571 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 1 30 theme Human 128:132 arg1 urine 152:156 Human beta-mannosidosis urine 128:156 Human beta-mannosidosis urine 128:156 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 2246252 1 31 theme high 230:233 arg1 chromatography 254:267 high performance liquid chromatography 230:267 high performance liquid chromatography on Partisil 10 SAX 230:286 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 2246252 0 32 theme novel 58:62 arg1 1-4-N-acetylglucosamine 31:53 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine 0:53 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine 0:53 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine, a novel compound occurring in urine of patients with beta-mannosidosis. 2246252 0 32 theme novel 58:62 arg1 compound 64:71 a novel compound 56:71 a novel compound 56:71 Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine, a novel compound occurring in urine of patients with beta-mannosidosis. 2246252 3 33 theme composition 552:562 arg1 analysis 564:571 sugar composition analysis 546:571 sugar composition analysis 546:571 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 1 34 theme performance 235:245 arg1 chromatography 254:267 high performance liquid chromatography 230:267 high performance liquid chromatography on Partisil 10 SAX 230:286 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 2246252 1 35 theme liquid 247:252 arg1 chromatography 254:267 high performance liquid chromatography 230:267 high performance liquid chromatography on Partisil 10 SAX 230:286 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 2246252 5 36 theme unknown 921:927 arg1 susceptible 985:995 susceptible 985:995 susceptible 985:995 The hitherto unknown linkage between sialic acid and mannose was shown to be susceptible to sialidase digestion. 2246252 5 36 theme unknown 921:927 arg1 linkage 929:935 The hitherto unknown linkage 908:935 The hitherto unknown linkage between sialic acid and mannose 908:967 The hitherto unknown linkage between sialic acid and mannose was shown to be susceptible to sialidase digestion. 2246252 3 37 theme conclusive 678:687 arg1 evidence 689:696 conclusive evidence 678:696 conclusive evidence for a novel urinary constituent 678:728 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 3 38 theme chromatography-mass 607:625 arg1 spectrometry 627:638 gas-liquid chromatography-mass spectrometry 596:638 gas-liquid chromatography-mass spectrometry 596:638 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 4 39 theme Man 888:890 arg1 compound 878:885 the major accumulating compound 855:885 the major accumulating compound 855:885 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 4 39 theme Man 888:890 arg1 1-4GlcNAc 897:905 Man beta 1-4GlcNAc 888:905 Man beta 1-4GlcNAc 888:905 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 1 40 theme beta-mannosidosis 134:150 arg1 urine 152:156 Human beta-mannosidosis urine 128:156 Human beta-mannosidosis urine 128:156 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 2246252 4 41 gly 2-6-sialylation 836:850 arg1 compound 878:885 the major accumulating compound 855:885 the major accumulating compound 855:885 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 4 41 gly 2-6-sialylation 836:850 arg1 1-4GlcNAc 897:905 Man beta 1-4GlcNAc 888:905 Man beta 1-4GlcNAc 888:905 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 3 42 theme alpha 737:741 arg1 beta 750:753 NeuAc alpha 2-6Man beta 731:753 NeuAc alpha 2-6Man beta 1-4GlcNAc 731:763 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 3 43 theme urinary 710:716 arg1 constituent 718:728 a novel urinary constituent 702:728 a novel urinary constituent 702:728 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 4 44 theme major 859:863 arg1 compound 878:885 the major accumulating compound 855:885 the major accumulating compound 855:885 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 4 44 theme major 859:863 arg1 1-4GlcNAc 897:905 Man beta 1-4GlcNAc 888:905 Man beta 1-4GlcNAc 888:905 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 2 45 theme sialic 359:364 arg1 compound 382:389 a sialic acid-containing compound 357:389 a sialic acid-containing compound 357:389 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 4 46 theme alpha 830:834 arg1 2-6-sialylation 836:850 an alpha 2-6-sialylation 827:850 an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc 827:905 This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. 2246252 1 47 from chromatography 254:267 arg1 SAX 284:286 Partisil 10 SAX 272:286 Partisil 10 SAX 272:286 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 2246252 3 48 theme NMR 656:658 arg1 spectroscopy 660:671 500-MHz 1H NMR spectroscopy 645:671 500-MHz 1H NMR spectroscopy 645:671 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 3 49 dep gave 673:676 arg1 1-4GlcNAc 755:763 NeuAc alpha 2-6Man beta 1-4GlcNAc 731:763 NeuAc alpha 2-6Man beta 1-4GlcNAc 731:763 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 2 50 theme disaccharide 301:312 arg1 1-4GlcNAc 323:331 the disaccharide Man beta 1-4GlcNAc 297:331 the disaccharide Man beta 1-4GlcNAc as the major component 297:354 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 3 51 theme oligosaccharide 499:513 arg1 characterization 475:490 Structural characterization 464:490 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy 464:671 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 2 52 theme % 422:422 arg1 amount 410:415 an amount 407:415 an amount of 10% 407:422 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 2 52 theme % 422:422 arg1 % 422:422 10% 420:422 10% 420:422 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 3 53 theme 500-MHz 645:651 arg1 spectroscopy 660:671 500-MHz 1H NMR spectroscopy 645:671 500-MHz 1H NMR spectroscopy 645:671 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 3 54 theme analogue 534:541 arg1 characterization 475:490 Structural characterization 464:490 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy 464:671 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 1 55 theme Partisil 272:279 arg1 SAX 284:286 Partisil 10 SAX 272:286 Partisil 10 SAX 272:286 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 2246252 2 56 located detected 395:402 arg1 amount 410:415 an amount 407:415 an amount of 10% 407:422 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 2 56 located detected 395:402 arg1 % 422:422 10% 420:422 10% 420:422 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 2 56 located detected 395:402 arg2 compound 382:389 a sialic acid-containing compound 357:389 a sialic acid-containing compound 357:389 Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid-containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. 2246252 3 57 theme 1H 653:654 arg1 spectroscopy 660:671 500-MHz 1H NMR spectroscopy 645:671 500-MHz 1H NMR spectroscopy 645:671 Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. 2246252 1 58 theme gel 178:180 arg1 chromatography 193:206 gel permeation chromatography 178:206 gel permeation chromatography on Bio-Gel P-2 178:221 Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. 12063266 4 0 theme oligosaccharides 675:690 arg1 concentration 653:665 the concentration 649:665 : (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) 643:799 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 5 1 theme fucose 1364:1369 arg1 effect 1349:1354 The agonistic effect 1335:1354 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro 1335:1437 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 1 2 theme peptides 135:142 arg1 mixture 99:105 a complex mixture 89:105 a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract 89:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 1 2 theme peptides 135:142 arg1 plasma 79:84 Human seminal plasma 65:84 Human seminal plasma 65:84 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 4 3 theme Significant 585:595 arg1 findings 597:604 Significant findings 585:604 Significant findings of our analyses 585:620 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 4 theme Lewis 874:878 arg1 epitopes 899:906 Lewis(x) and/or Lewis(y) epitopes 874:906 Lewis(x) and/or Lewis(y) epitopes 874:906 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 0 5 from expression 4:13 arg1 plasma 57:62 human seminal plasma 43:62 human seminal plasma 43:62 The expression of free oligosaccharides in human seminal plasma. 12063266 1 6 gly glycopeptides 145:157 arg2 glycopeptides 145:157 glycopeptides 145:157 glycopeptides 145:157 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 4 7 theme following 634:642 arg1 oligosaccharides 1051:1066 the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides 630:1066 the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides 630:1332 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 2 8 theme agonistic 319:327 arg1 effects 329:335 agonistic effects 319:335 agonistic effects on sperm-egg binding 319:356 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 2 9 from suppression 287:297 arg1 binding 350:356 sperm-egg binding 340:356 sperm-egg binding 340:356 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 2 10 theme immune 302:307 arg1 response 309:316 immune response 302:316 immune response 302:316 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 4 11 theme Lewis 890:894 arg1 epitopes 899:906 Lewis(x) and/or Lewis(y) epitopes 874:906 Lewis(x) and/or Lewis(y) epitopes 874:906 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 12 dep concentration 653:665 arg1 forms 739:743 difucosylated forms 725:743 difucosylated forms of the disaccharide lactose 725:771 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 12 dep concentration 653:665 arg1 components 783:792 major components 777:792 major components 777:792 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 12 dep concentration 653:665 arg1 i 646:646 i 646:646 i 646:646 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 12 dep concentration 653:665 arg1 mg/ml 703:707 0.3-0.4 mg/ml 695:707 0.3-0.4 mg/ml 695:707 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 12 dep concentration 653:665 arg1 mono- 715:719 (ii) mono- 710:719 (ii) mono- 710:719 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 5 13 theme fucosylated 1375:1385 arg1 glycoconjugates 1387:1401 fucosylated glycoconjugates 1375:1401 fucosylated glycoconjugates 1375:1401 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 4 14 theme end 968:970 arg1 GlcNAcbeta1-3/4Glc 982:999 GlcNAcbeta1-3/4Glc 982:999 GlcNAcbeta1-3/4Glc 982:999 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 14 theme end 968:970 arg1 sequence 972:979 the reducing end sequence 955:979 the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides 955:1044 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 15 theme human 1306:1310 arg1 oligosaccharides 1317:1332 human milk oligosaccharides 1306:1332 human milk oligosaccharides 1306:1332 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 16 theme milk 1206:1209 arg1 glycans 1211:1217 human milk glycans 1200:1217 human milk glycans 1200:1217 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 5 17 theme glycoconjugates 1387:1401 arg1 effect 1349:1354 The agonistic effect 1335:1354 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro 1335:1437 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 4 18 theme type 1144:1147 arg1 Galbeta1-3GlcNAc 1162:1177 Galbeta1-3GlcNAc 1162:1177 Galbeta1-3GlcNAc 1162:1177 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 18 theme type 1144:1147 arg1 sequences 1151:1159 the type 1 sequences 1140:1159 type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides 1106:1332 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 3 19 theme total 540:544 arg1 glycoconjugates 546:560 the total glycoconjugates 536:560 the total glycoconjugates within seminal plasma 536:582 Fractionation followed by biophysical analyses revealed that free oligosaccharides constitute a major component of the total glycoconjugates within seminal plasma. 12063266 4 20 theme human 1200:1204 arg1 glycans 1211:1217 human milk glycans 1200:1217 human milk glycans 1200:1217 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 5 21 theme agonistic 1339:1347 arg1 effect 1349:1354 The agonistic effect 1335:1354 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro 1335:1437 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 3 22 theme biophysical 447:457 arg1 analyses 459:466 biophysical analyses 447:466 biophysical analyses 447:466 Fractionation followed by biophysical analyses revealed that free oligosaccharides constitute a major component of the total glycoconjugates within seminal plasma. 12063266 1 23 theme Human 65:69 arg1 mixture 99:105 a complex mixture 89:105 a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract 89:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 1 23 theme Human 65:69 arg1 plasma 79:84 Human seminal plasma 65:84 Human seminal plasma 65:84 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 4 24 contain carry 868:872 arg1 subset 916:921 a subset 914:921 a subset 914:921 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 24 contain carry 868:872 arg1 v 1048:1048 v 1048:1048 v 1048:1048 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 24 contain carry 868:872 arg1 of 923:924 of 923:924 of 923:924 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 24 contain carry 868:872 arg2 epitopes 899:906 Lewis(x) and/or Lewis(y) epitopes 874:906 Lewis(x) and/or Lewis(y) epitopes 874:906 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 24 contain carry 868:872 arg1 oligosaccharides 823:838 the remaining oligosaccharides 809:838 the remaining oligosaccharides 809:838 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 24 contain carry 868:872 arg1 express 947:953 express 947:953 express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides 947:1044 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 24 contain carry 868:872 arg1 iv 910:911 iv 910:911 iv 910:911 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 24 contain carry 868:872 arg1 rich 849:852 rich 849:852 rich 849:852 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 1 25 theme glycopeptides 145:157 arg1 mixture 99:105 a complex mixture 89:105 a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract 89:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 1 25 theme glycopeptides 145:157 arg1 plasma 79:84 Human seminal plasma 65:84 Human seminal plasma 65:84 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 4 26 gly difucosylated 725:737 arg1 lactose 765:771 the disaccharide lactose 748:771 the disaccharide lactose 748:771 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 26 gly difucosylated 725:737 arg1 components 783:792 major components 777:792 major components 777:792 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 26 gly difucosylated 725:737 arg1 mono- 715:719 (ii) mono- 710:719 (ii) mono- 710:719 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 26 gly difucosylated 725:737 arg1 forms 739:743 difucosylated forms 725:743 difucosylated forms of the disaccharide lactose 725:771 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 5 27 theme female 1520:1525 arg1 tract 1540:1544 the female reproductive tract 1516:1544 the female reproductive tract 1516:1544 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 4 28 theme many 801:804 arg1 oligosaccharides 1051:1066 the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides 630:1066 the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides 630:1332 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 2 29 from effects 329:335 arg1 binding 350:356 sperm-egg binding 340:356 sperm-egg binding 340:356 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 1 30 theme seminal 71:77 arg1 mixture 99:105 a complex mixture 89:105 a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract 89:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 1 30 theme seminal 71:77 arg1 plasma 79:84 Human seminal plasma 65:84 Human seminal plasma 65:84 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 4 31 dep oligosaccharides 1051:1066 arg1 express 1098:1104 express 1098:1104 express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides 1098:1332 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 32 theme oligosaccharides 1272:1287 arg1 glycans 1211:1217 human milk glycans 1200:1217 human milk glycans 1200:1217 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 32 theme oligosaccharides 1272:1287 arg1 diversity 1244:1252 the structural diversity 1229:1252 (vi) the structural diversity of seminal plasma oligosaccharides 1224:1287 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 32 theme oligosaccharides 1272:1287 arg1 less 1296:1299 less 1296:1299 less 1296:1299 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 33 theme remaining 813:821 arg1 subset 916:921 a subset 914:921 a subset 914:921 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 33 theme remaining 813:821 arg1 v 1048:1048 v 1048:1048 v 1048:1048 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 33 theme remaining 813:821 arg1 of 923:924 of 923:924 of 923:924 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 33 theme remaining 813:821 arg1 oligosaccharides 823:838 the remaining oligosaccharides 809:838 the remaining oligosaccharides 809:838 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 33 theme remaining 813:821 arg1 express 947:953 express 947:953 express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides 947:1044 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 33 theme remaining 813:821 arg1 iv 910:911 iv 910:911 iv 910:911 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 33 theme remaining 813:821 arg1 rich 849:852 rich 849:852 rich 849:852 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 3 34 theme seminal 569:575 arg1 plasma 577:582 seminal plasma 569:582 seminal plasma 569:582 Fractionation followed by biophysical analyses revealed that free oligosaccharides constitute a major component of the total glycoconjugates within seminal plasma. 12063266 5 35 theme human 1406:1410 arg1 binding 1422:1428 human sperm-egg binding 1406:1428 human sperm-egg binding in vitro 1406:1437 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 2 36 theme embryo 413:418 arg1 implantation 387:398 successful implantation 376:398 successful implantation of the human embryo 376:418 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 4 37 theme plasma 1265:1270 arg1 oligosaccharides 1272:1287 seminal plasma oligosaccharides 1257:1287 seminal plasma oligosaccharides 1257:1287 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 38 dep mono- 715:719 arg1 ii 711:712 ii 711:712 ii 711:712 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 5 39 gly fucosylated 1453:1463 arg1 oligosaccharides 1465:1480 fucosylated oligosaccharides 1453:1480 fucosylated oligosaccharides 1453:1480 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 1 40 theme prostaglandins 164:177 arg1 mixture 99:105 a complex mixture 89:105 a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract 89:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 1 40 theme prostaglandins 164:177 arg1 plasma 79:84 Human seminal plasma 65:84 Human seminal plasma 65:84 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 0 41 theme free 18:21 arg1 oligosaccharides 23:38 free oligosaccharides 18:38 free oligosaccharides 18:38 The expression of free oligosaccharides in human seminal plasma. 12063266 4 42 theme seminal 1257:1263 arg1 oligosaccharides 1272:1287 seminal plasma oligosaccharides 1257:1287 seminal plasma oligosaccharides 1257:1287 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 3 43 theme glycoconjugates 546:560 arg1 component 523:531 a major component 515:531 a major component of the total glycoconjugates within seminal plasma 515:582 Fractionation followed by biophysical analyses revealed that free oligosaccharides constitute a major component of the total glycoconjugates within seminal plasma. 12063266 4 44 theme milk 1312:1315 arg1 oligosaccharides 1317:1332 human milk oligosaccharides 1306:1332 human milk oligosaccharides 1306:1332 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 2 45 theme fluid 253:257 arg1 components 234:243 The components 230:243 The components of this fluid 230:257 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 1 46 theme complex 91:97 arg1 mixture 99:105 a complex mixture 89:105 a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract 89:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 1 46 theme complex 91:97 arg1 plasma 79:84 Human seminal plasma 65:84 Human seminal plasma 65:84 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 4 47 theme milk 1024:1027 arg1 oligosaccharides 1029:1044 human milk oligosaccharides 1018:1044 human milk oligosaccharides 1018:1044 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 2 48 theme implantation 387:398 arg1 effects 329:335 agonistic effects 319:335 agonistic effects on sperm-egg binding 319:356 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 2 48 theme implantation 387:398 arg1 promotion 363:371 promotion 363:371 promotion of successful implantation of the human embryo 363:418 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 2 48 theme implantation 387:398 arg1 suppression 287:297 the suppression 283:297 the suppression of immune response 283:316 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 4 49 dep rich 849:852 arg1 subset 916:921 a subset 914:921 a subset 914:921 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 49 dep rich 849:852 arg1 v 1048:1048 v 1048:1048 v 1048:1048 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 49 dep rich 849:852 arg1 of 923:924 of 923:924 of 923:924 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 49 dep rich 849:852 arg1 oligosaccharides 930:945 the oligosaccharides 926:945 the oligosaccharides 926:945 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 49 dep rich 849:852 arg1 oligosaccharides 823:838 the remaining oligosaccharides 809:838 the remaining oligosaccharides 809:838 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 49 dep rich 849:852 arg1 express 947:953 express 947:953 express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides 947:1044 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 49 dep rich 849:852 arg1 iv 910:911 iv 910:911 iv 910:911 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 49 dep rich 849:852 arg1 rich 849:852 rich 849:852 rich 849:852 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 3 50 theme free 482:485 arg1 oligosaccharides 487:502 free oligosaccharides 482:502 free oligosaccharides 482:502 Fractionation followed by biophysical analyses revealed that free oligosaccharides constitute a major component of the total glycoconjugates within seminal plasma. 12063266 5 51 from effect 1349:1354 arg1 binding 1422:1428 human sperm-egg binding 1406:1428 human sperm-egg binding in vitro 1406:1437 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 4 52 theme human 1018:1022 arg1 oligosaccharides 1029:1044 human milk oligosaccharides 1018:1044 human milk oligosaccharides 1018:1044 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 2 53 theme successful 376:385 arg1 implantation 387:398 successful implantation 376:398 successful implantation of the human embryo 376:418 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 0 54 theme oligosaccharides 23:38 arg1 expression 4:13 The expression 0:13 The expression of free oligosaccharides in human seminal plasma 0:62 The expression of free oligosaccharides in human seminal plasma. 12063266 4 55 theme structural 1233:1242 arg1 diversity 1244:1252 the structural diversity 1229:1252 (vi) the structural diversity of seminal plasma oligosaccharides 1224:1287 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 55 theme structural 1233:1242 arg1 less 1296:1299 less 1296:1299 less 1296:1299 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 5 56 theme reproductive 1527:1538 arg1 tract 1540:1544 the female reproductive tract 1516:1544 the female reproductive tract 1516:1544 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 2 57 theme human 407:411 arg1 embryo 413:418 the human embryo 403:418 the human embryo 403:418 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 5 58 theme fucosylated 1453:1463 arg1 oligosaccharides 1465:1480 fucosylated oligosaccharides 1453:1480 fucosylated oligosaccharides 1453:1480 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 0 59 theme seminal 49:55 arg1 plasma 57:62 human seminal plasma 43:62 human seminal plasma 43:62 The expression of free oligosaccharides in human seminal plasma. 12063266 5 60 gly fucosylated 1375:1385 arg1 glycoconjugates 1387:1401 fucosylated glycoconjugates 1375:1401 fucosylated glycoconjugates 1375:1401 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 5 61 theme sperm-egg 1412:1420 arg1 binding 1422:1428 human sperm-egg binding 1406:1428 human sperm-egg binding in vitro 1406:1437 The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract. 12063266 0 62 theme human 43:47 arg1 plasma 57:62 human seminal plasma 43:62 human seminal plasma 43:62 The expression of free oligosaccharides in human seminal plasma. 12063266 1 63 gly glycoproteins 120:132 arg1 glycoproteins 120:132 glycoproteins 120:132 glycoproteins 120:132 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 2 64 from promotion 363:371 arg1 binding 350:356 sperm-egg binding 340:356 sperm-egg binding 340:356 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 2 65 theme response 309:316 arg1 effects 329:335 agonistic effects 319:335 agonistic effects on sperm-egg binding 319:356 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 2 65 theme response 309:316 arg1 promotion 363:371 promotion 363:371 promotion of successful implantation of the human embryo 363:418 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 2 65 theme response 309:316 arg1 suppression 287:297 the suppression 283:297 the suppression of immune response 283:316 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 4 66 dep diversity 1244:1252 arg1 vi 1225:1226 vi 1225:1226 vi 1225:1226 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 1 67 theme glycoproteins 120:132 arg1 mixture 99:105 a complex mixture 89:105 a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract 89:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 1 67 theme glycoproteins 120:132 arg1 plasma 79:84 Human seminal plasma 65:84 Human seminal plasma 65:84 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 1 68 theme proteins 110:117 arg1 mixture 99:105 a complex mixture 89:105 a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract 89:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 1 68 theme proteins 110:117 arg1 plasma 79:84 Human seminal plasma 65:84 Human seminal plasma 65:84 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 4 69 theme difucosylated 725:737 arg1 components 783:792 major components 777:792 major components 777:792 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 69 theme difucosylated 725:737 arg1 mono- 715:719 (ii) mono- 710:719 (ii) mono- 710:719 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 69 theme difucosylated 725:737 arg1 forms 739:743 difucosylated forms 725:743 difucosylated forms of the disaccharide lactose 725:771 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 70 theme analyses 613:620 arg1 findings 597:604 Significant findings 585:604 Significant findings of our analyses 585:620 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 71 theme disaccharide 752:763 arg1 lactose 765:771 the disaccharide lactose 748:771 the disaccharide lactose 748:771 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 72 from fucose 857:862 arg1 subset 916:921 a subset 914:921 a subset 914:921 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 72 from fucose 857:862 arg1 v 1048:1048 v 1048:1048 v 1048:1048 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 72 from fucose 857:862 arg1 of 923:924 of 923:924 of 923:924 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 72 from fucose 857:862 arg1 oligosaccharides 823:838 the remaining oligosaccharides 809:838 the remaining oligosaccharides 809:838 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 72 from fucose 857:862 arg1 express 947:953 express 947:953 express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides 947:1044 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 72 from fucose 857:862 arg1 iv 910:911 iv 910:911 iv 910:911 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 72 from fucose 857:862 arg1 rich 849:852 rich 849:852 rich 849:852 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 73 theme lactose 765:771 arg1 components 783:792 major components 777:792 major components 777:792 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 73 theme lactose 765:771 arg1 mono- 715:719 (ii) mono- 710:719 (ii) mono- 710:719 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 73 theme lactose 765:771 arg1 forms 739:743 difucosylated forms 725:743 difucosylated forms of the disaccharide lactose 725:771 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 74 theme free 670:673 arg1 oligosaccharides 675:690 free oligosaccharides 670:690 free oligosaccharides 670:690 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 1 75 theme male 205:208 arg1 tract 223:227 the male reproductive tract 201:227 the male reproductive tract 201:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 4 76 from oligosaccharides 1051:1066 arg1 plasma 1079:1084 seminal plasma 1071:1084 seminal plasma 1071:1084 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 2 77 theme sperm-egg 340:348 arg1 binding 350:356 sperm-egg binding 340:356 sperm-egg binding 340:356 The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. 12063266 1 78 theme reproductive 210:221 arg1 tract 223:227 the male reproductive tract 201:227 the male reproductive tract 201:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 12063266 4 79 from rich 849:852 arg1 fucose 857:862 fucose 857:862 fucose 857:862 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 80 theme major 777:781 arg1 components 783:792 major components 777:792 major components 777:792 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 80 theme major 777:781 arg1 mono- 715:719 (ii) mono- 710:719 (ii) mono- 710:719 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 80 theme major 777:781 arg1 forms 739:743 difucosylated forms 725:743 difucosylated forms of the disaccharide lactose 725:771 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 81 theme seminal 1071:1077 arg1 plasma 1079:1084 seminal plasma 1071:1084 seminal plasma 1071:1084 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 3 82 theme major 517:521 arg1 component 523:531 a major component 515:531 a major component of the total glycoconjugates within seminal plasma 515:582 Fractionation followed by biophysical analyses revealed that free oligosaccharides constitute a major component of the total glycoconjugates within seminal plasma. 12063266 4 83 theme reducing 959:966 arg1 GlcNAcbeta1-3/4Glc 982:999 GlcNAcbeta1-3/4Glc 982:999 GlcNAcbeta1-3/4Glc 982:999 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 4 83 theme reducing 959:966 arg1 sequence 972:979 the reducing end sequence 955:979 the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides 955:1044 Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y) epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc) but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. 12063266 1 84 theme tract 223:227 arg1 organs 191:196 organs 191:196 organs of the male reproductive tract 191:227 Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. 10460833 7 0 theme inconsistent 1325:1336 arg1 one 1338:1340 a scattered inconsistent one 1313:1340 a scattered inconsistent one 1313:1340 Sialidase treatment of whole cells caused a change of VE-cadherin immunofluorescence from a continuous and netlike superstructural organization to a scattered inconsistent one. 10460833 6 1 theme Ca 985:986 arg1 -depletion 991:1000 Ca(2+)-depletion 985:1000 Ca(2+)-depletion 985:1000 Ca(2+)-depletion, performed on cultured endothelial cells, resulted in a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions. 10460833 1 2 theme cultured 159:166 arg1 cells 206:210 cultured human umbilical cord vein endothelial cells 159:210 cultured human umbilical cord vein endothelial cells 159:210 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 6 3 theme VE-cadherin 1095:1105 arg1 disappearance 1078:1090 a reversible complete disappearance 1056:1090 a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions 1056:1163 Ca(2+)-depletion, performed on cultured endothelial cells, resulted in a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions. 10460833 2 4 theme N. 396:397 arg1 Oligosaccharides 399:414 endoproteinase Asp N. Oligosaccharides 377:414 endoproteinase Asp N. Oligosaccharides 377:414 VE-cadherin was metabolically radiolabeled with d-[6-(3)H]glucosamine, isolated by immunoprecipitation, purified by SDS-PAGE and in-gel digested with endoproteinase Asp N. Oligosaccharides were sequentially released from resulting glycopeptides and analyzed by chromatographic profiling. 10460833 5 5 from junctions 881:889 arg1 cells 906:910 endothelial cells 894:910 endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers 894:982 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 1 6 theme human 168:172 arg1 cells 206:210 cultured human umbilical cord vein endothelial cells 159:210 cultured human umbilical cord vein endothelial cells 159:210 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 5 7 theme sialic 817:822 arg1 acids 824:828 sialic acids 817:828 sialic acids 817:828 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 3 8 contain carries 553:559 arg1 VE-cadherin 541:551 VE-cadherin 541:551 VE-cadherin 541:551 The results revealed that VE-cadherin carries predominantly sialylated diantennary and hybrid-type glycans in addition to some triantennary and high mannose-type species. 10460833 3 8 contain carries 553:559 arg2 glycans 614:620 predominantly sialylated diantennary and hybrid-type glycans 561:620 glycans 614:620 The results revealed that VE-cadherin carries predominantly sialylated diantennary and hybrid-type glycans in addition to some triantennary and high mannose-type species. 10460833 3 8 contain carries 553:559 arg2 diantennary 586:596 diantennary 586:596 diantennary 586:596 The results revealed that VE-cadherin carries predominantly sialylated diantennary and hybrid-type glycans in addition to some triantennary and high mannose-type species. 10460833 5 9 theme acids 824:828 arg1 labeling 789:796 Immunohistochemical labeling 769:796 Immunohistochemical labeling of VE-cadherin and sialic acids 769:828 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 4 10 located found 740:744 arg1 amounts 755:761 trace amounts 749:761 trace amounts 749:761 Highly branched, tetraantennary oligosaccharides were found in trace amounts only. 10460833 4 10 located found 740:744 arg2 oligosaccharides 718:733 Highly branched, tetraantennary oligosaccharides 686:733 Highly branched, tetraantennary oligosaccharides 686:733 Highly branched, tetraantennary oligosaccharides were found in trace amounts only. 10460833 3 11 theme hybrid-type 602:612 arg1 glycans 614:620 predominantly sialylated diantennary and hybrid-type glycans 561:620 glycans 614:620 The results revealed that VE-cadherin carries predominantly sialylated diantennary and hybrid-type glycans in addition to some triantennary and high mannose-type species. 10460833 1 12 theme glycosylation 69:81 arg1 pattern 83:89 The glycosylation pattern 65:89 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, 65:211 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 5 13 theme cultured 952:959 arg1 monolayers 973:982 cultured endothelial monolayers 952:982 cultured endothelial monolayers 952:982 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 5 14 theme veins 941:945 arg1 cells 906:910 endothelial cells 894:910 endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers 894:982 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 4 15 theme branched 693:700 arg1 oligosaccharides 718:733 Highly branched, tetraantennary oligosaccharides 686:733 Highly branched, tetraantennary oligosaccharides 686:733 Highly branched, tetraantennary oligosaccharides were found in trace amounts only. 10460833 1 16 theme vein 189:192 arg1 cells 206:210 cultured human umbilical cord vein endothelial cells 159:210 cultured human umbilical cord vein endothelial cells 159:210 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 1 17 theme umbilical 174:182 arg1 cells 206:210 cultured human umbilical cord vein endothelial cells 159:210 cultured human umbilical cord vein endothelial cells 159:210 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 6 18 theme complete 1069:1076 arg1 disappearance 1078:1090 a reversible complete disappearance 1056:1090 a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions 1056:1163 Ca(2+)-depletion, performed on cultured endothelial cells, resulted in a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions. 10460833 7 19 theme cells 1195:1199 arg1 treatment 1176:1184 Sialidase treatment 1166:1184 Sialidase treatment of whole cells 1166:1199 Sialidase treatment of whole cells caused a change of VE-cadherin immunofluorescence from a continuous and netlike superstructural organization to a scattered inconsistent one. 10460833 7 20 theme superstructural 1281:1295 arg1 organization 1297:1308 a continuous and netlike superstructural organization 1256:1308 a continuous and netlike superstructural organization 1256:1308 Sialidase treatment of whole cells caused a change of VE-cadherin immunofluorescence from a continuous and netlike superstructural organization to a scattered inconsistent one. 10460833 1 21 theme cord 184:187 arg1 cells 206:210 cultured human umbilical cord vein endothelial cells 159:210 cultured human umbilical cord vein endothelial cells 159:210 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 7 22 theme netlike 1273:1279 arg1 organization 1297:1308 a continuous and netlike superstructural organization 1256:1308 a continuous and netlike superstructural organization 1256:1308 Sialidase treatment of whole cells caused a change of VE-cadherin immunofluorescence from a continuous and netlike superstructural organization to a scattered inconsistent one. 10460833 5 23 theme intercellular 867:879 arg1 junctions 881:889 the intercellular junctions 863:889 the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers 863:982 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 2 24 dep H 283:283 arg1 3 281:281 3 281:281 3 281:281 VE-cadherin was metabolically radiolabeled with d-[6-(3)H]glucosamine, isolated by immunoprecipitation, purified by SDS-PAGE and in-gel digested with endoproteinase Asp N. Oligosaccharides were sequentially released from resulting glycopeptides and analyzed by chromatographic profiling. 10460833 1 25 theme human 94:98 arg1 VE-cadherin 131:141 VE-cadherin 131:141 VE-cadherin 131:141 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 1 25 theme human 94:98 arg1 cadherin 121:128 human vascular endothelial cadherin 94:128 human vascular endothelial cadherin (VE-cadherin) 94:142 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 2 26 theme endoproteinase 377:390 arg1 Oligosaccharides 399:414 endoproteinase Asp N. Oligosaccharides 377:414 endoproteinase Asp N. Oligosaccharides 377:414 VE-cadherin was metabolically radiolabeled with d-[6-(3)H]glucosamine, isolated by immunoprecipitation, purified by SDS-PAGE and in-gel digested with endoproteinase Asp N. Oligosaccharides were sequentially released from resulting glycopeptides and analyzed by chromatographic profiling. 10460833 5 27 theme human 915:919 arg1 arteries 931:938 human umbilical arteries 915:938 human umbilical arteries 915:938 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 6 28 theme reversible 1058:1067 arg1 disappearance 1078:1090 a reversible complete disappearance 1056:1090 a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions 1056:1163 Ca(2+)-depletion, performed on cultured endothelial cells, resulted in a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions. 10460833 8 29 theme cell 1350:1353 arg1 acids 1370:1374 cell surface sialic acids 1350:1374 cell surface sialic acids 1350:1374 Hence, cell surface sialic acids might play a role in VE-cadherin organization. 10460833 1 30 theme vascular 100:107 arg1 VE-cadherin 131:141 VE-cadherin 131:141 VE-cadherin 131:141 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 1 30 theme vascular 100:107 arg1 cadherin 121:128 human vascular endothelial cadherin 94:128 human vascular endothelial cadherin (VE-cadherin) 94:142 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 1 31 theme endothelial 194:204 arg1 cells 206:210 cultured human umbilical cord vein endothelial cells 159:210 cultured human umbilical cord vein endothelial cells 159:210 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 0 32 theme vascular 26:33 arg1 glycans 56:62 human vascular endothelial cadherin glycans 20:62 human vascular endothelial cadherin glycans 20:62 Characterization of human vascular endothelial cadherin glycans. 10460833 4 33 dep branched 693:700 arg1 tetraantennary 703:716 tetraantennary 703:716 tetraantennary 703:716 Highly branched, tetraantennary oligosaccharides were found in trace amounts only. 10460833 1 34 theme endothelial 109:119 arg1 VE-cadherin 131:141 VE-cadherin 131:141 VE-cadherin 131:141 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 1 34 theme endothelial 109:119 arg1 cadherin 121:128 human vascular endothelial cadherin 94:128 human vascular endothelial cadherin (VE-cadherin) 94:142 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 0 35 theme human 20:24 arg1 glycans 56:62 human vascular endothelial cadherin glycans 20:62 human vascular endothelial cadherin glycans 20:62 Characterization of human vascular endothelial cadherin glycans. 10460833 7 36 theme Sialidase 1166:1174 arg1 treatment 1176:1184 Sialidase treatment 1166:1184 Sialidase treatment of whole cells 1166:1199 Sialidase treatment of whole cells caused a change of VE-cadherin immunofluorescence from a continuous and netlike superstructural organization to a scattered inconsistent one. 10460833 1 37 theme cadherin 121:128 arg1 pattern 83:89 The glycosylation pattern 65:89 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, 65:211 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 3 38 dep species 677:683 arg1 addition 625:632 addition 625:632 addition 625:632 The results revealed that VE-cadherin carries predominantly sialylated diantennary and hybrid-type glycans in addition to some triantennary and high mannose-type species. 10460833 0 39 theme cadherin 47:54 arg1 glycans 56:62 human vascular endothelial cadherin glycans 20:62 human vascular endothelial cadherin glycans 20:62 Characterization of human vascular endothelial cadherin glycans. 10460833 4 40 theme trace 749:753 arg1 amounts 755:761 trace amounts 749:761 trace amounts 749:761 Highly branched, tetraantennary oligosaccharides were found in trace amounts only. 10460833 5 41 theme VE-cadherin 801:811 arg1 labeling 789:796 Immunohistochemical labeling 769:796 Immunohistochemical labeling of VE-cadherin and sialic acids 769:828 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 2 42 attach released 434:441 arg1 glycopeptides 458:470 resulting glycopeptides 448:470 resulting glycopeptides 448:470 VE-cadherin was metabolically radiolabeled with d-[6-(3)H]glucosamine, isolated by immunoprecipitation, purified by SDS-PAGE and in-gel digested with endoproteinase Asp N. Oligosaccharides were sequentially released from resulting glycopeptides and analyzed by chromatographic profiling. 10460833 2 42 attach released 434:441 arg2 Oligosaccharides 399:414 endoproteinase Asp N. Oligosaccharides 377:414 endoproteinase Asp N. Oligosaccharides 377:414 VE-cadherin was metabolically radiolabeled with d-[6-(3)H]glucosamine, isolated by immunoprecipitation, purified by SDS-PAGE and in-gel digested with endoproteinase Asp N. Oligosaccharides were sequentially released from resulting glycopeptides and analyzed by chromatographic profiling. 10460833 8 43 theme surface 1355:1361 arg1 acids 1370:1374 cell surface sialic acids 1350:1374 cell surface sialic acids 1350:1374 Hence, cell surface sialic acids might play a role in VE-cadherin organization. 10460833 6 44 theme acid 1132:1135 arg1 disappearance 1078:1090 a reversible complete disappearance 1056:1090 a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions 1056:1163 Ca(2+)-depletion, performed on cultured endothelial cells, resulted in a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions. 10460833 0 45 theme endothelial 35:45 arg1 glycans 56:62 human vascular endothelial cadherin glycans 20:62 human vascular endothelial cadherin glycans 20:62 Characterization of human vascular endothelial cadherin glycans. 10460833 5 46 theme endothelial 961:971 arg1 monolayers 973:982 cultured endothelial monolayers 952:982 cultured endothelial monolayers 952:982 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 2 47 theme chromatographic 488:502 arg1 profiling 504:512 chromatographic profiling 488:512 chromatographic profiling 488:512 VE-cadherin was metabolically radiolabeled with d-[6-(3)H]glucosamine, isolated by immunoprecipitation, purified by SDS-PAGE and in-gel digested with endoproteinase Asp N. Oligosaccharides were sequentially released from resulting glycopeptides and analyzed by chromatographic profiling. 10460833 2 48 theme resulting 448:456 arg1 glycopeptides 458:470 resulting glycopeptides 448:470 resulting glycopeptides 448:470 VE-cadherin was metabolically radiolabeled with d-[6-(3)H]glucosamine, isolated by immunoprecipitation, purified by SDS-PAGE and in-gel digested with endoproteinase Asp N. Oligosaccharides were sequentially released from resulting glycopeptides and analyzed by chromatographic profiling. 10460833 5 49 theme umbilical 921:929 arg1 arteries 931:938 human umbilical arteries 915:938 human umbilical arteries 915:938 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 5 50 theme endothelial 894:904 arg1 cells 906:910 endothelial cells 894:910 endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers 894:982 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 5 51 theme monolayers 973:982 arg1 cells 906:910 endothelial cells 894:910 endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers 894:982 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 0 52 theme glycans 56:62 arg1 Characterization 0:15 Characterization 0:15 Characterization of human vascular endothelial cadherin glycans. 0:63 Characterization of human vascular endothelial cadherin glycans. 10460833 6 53 theme endothelial 1025:1035 arg1 cells 1037:1041 cultured endothelial cells 1016:1041 cultured endothelial cells 1016:1041 Ca(2+)-depletion, performed on cultured endothelial cells, resulted in a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions. 10460833 3 54 theme triantennary 642:653 arg1 species 677:683 some triantennary and high mannose-type species 637:683 some triantennary and high mannose-type species 637:683 The results revealed that VE-cadherin carries predominantly sialylated diantennary and hybrid-type glycans in addition to some triantennary and high mannose-type species. 10460833 8 55 theme sialic 1363:1368 arg1 acids 1370:1374 cell surface sialic acids 1350:1374 cell surface sialic acids 1350:1374 Hence, cell surface sialic acids might play a role in VE-cadherin organization. 10460833 3 56 dep diantennary 586:596 arg1 sialylated 575:584 sialylated 575:584 sialylated 575:584 The results revealed that VE-cadherin carries predominantly sialylated diantennary and hybrid-type glycans in addition to some triantennary and high mannose-type species. 10460833 6 57 theme cultured 1016:1023 arg1 cells 1037:1041 cultured endothelial cells 1016:1041 cultured endothelial cells 1016:1041 Ca(2+)-depletion, performed on cultured endothelial cells, resulted in a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions. 10460833 7 58 theme immunofluorescence 1232:1249 arg1 change 1210:1215 a change 1208:1215 a change of VE-cadherin immunofluorescence 1208:1249 Sialidase treatment of whole cells caused a change of VE-cadherin immunofluorescence from a continuous and netlike superstructural organization to a scattered inconsistent one. 10460833 2 59 gly glycopeptides 458:470 arg2 glycopeptides 458:470 resulting glycopeptides 448:470 resulting glycopeptides 448:470 VE-cadherin was metabolically radiolabeled with d-[6-(3)H]glucosamine, isolated by immunoprecipitation, purified by SDS-PAGE and in-gel digested with endoproteinase Asp N. Oligosaccharides were sequentially released from resulting glycopeptides and analyzed by chromatographic profiling. 10460833 3 60 theme high 659:662 arg1 species 677:683 some triantennary and high mannose-type species 637:683 some triantennary and high mannose-type species 637:683 The results revealed that VE-cadherin carries predominantly sialylated diantennary and hybrid-type glycans in addition to some triantennary and high mannose-type species. 10460833 6 61 theme all 1121:1123 arg1 acid 1132:1135 almost all sialic acid 1114:1135 almost all sialic acid staining from the junctions 1114:1163 Ca(2+)-depletion, performed on cultured endothelial cells, resulted in a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions. 10460833 5 62 theme Immunohistochemical 769:787 arg1 labeling 789:796 Immunohistochemical labeling 769:796 Immunohistochemical labeling of VE-cadherin and sialic acids 769:828 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 2 63 theme d-[6- 275:279 arg1 glucosamine 285:295 d-[6-(3)H]glucosamine 275:295 d-[6-(3)H]glucosamine 275:295 VE-cadherin was metabolically radiolabeled with d-[6-(3)H]glucosamine, isolated by immunoprecipitation, purified by SDS-PAGE and in-gel digested with endoproteinase Asp N. Oligosaccharides were sequentially released from resulting glycopeptides and analyzed by chromatographic profiling. 10460833 8 64 theme VE-cadherin 1397:1407 arg1 organization 1409:1420 VE-cadherin organization 1397:1420 VE-cadherin organization 1397:1420 Hence, cell surface sialic acids might play a role in VE-cadherin organization. 10460833 7 65 theme continuous 1258:1267 arg1 organization 1297:1308 a continuous and netlike superstructural organization 1256:1308 a continuous and netlike superstructural organization 1256:1308 Sialidase treatment of whole cells caused a change of VE-cadherin immunofluorescence from a continuous and netlike superstructural organization to a scattered inconsistent one. 10460833 1 66 gly glycosylation 69:81 arg1 VE-cadherin 131:141 VE-cadherin 131:141 VE-cadherin 131:141 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 1 66 gly glycosylation 69:81 arg1 cadherin 121:128 human vascular endothelial cadherin 94:128 human vascular endothelial cadherin (VE-cadherin) 94:142 The glycosylation pattern of human vascular endothelial cadherin (VE-cadherin), purified from cultured human umbilical cord vein endothelial cells, was analyzed. 10460833 6 67 theme sialic 1125:1130 arg1 acid 1132:1135 almost all sialic acid 1114:1135 almost all sialic acid staining from the junctions 1114:1163 Ca(2+)-depletion, performed on cultured endothelial cells, resulted in a reversible complete disappearance of VE-cadherin and of almost all sialic acid staining from the junctions. 10460833 3 68 theme mannose-type 664:675 arg1 species 677:683 some triantennary and high mannose-type species 637:683 some triantennary and high mannose-type species 637:683 The results revealed that VE-cadherin carries predominantly sialylated diantennary and hybrid-type glycans in addition to some triantennary and high mannose-type species. 10460833 2 69 theme Asp 392:394 arg1 Oligosaccharides 399:414 endoproteinase Asp N. Oligosaccharides 377:414 endoproteinase Asp N. Oligosaccharides 377:414 VE-cadherin was metabolically radiolabeled with d-[6-(3)H]glucosamine, isolated by immunoprecipitation, purified by SDS-PAGE and in-gel digested with endoproteinase Asp N. Oligosaccharides were sequentially released from resulting glycopeptides and analyzed by chromatographic profiling. 10460833 7 70 theme VE-cadherin 1220:1230 arg1 immunofluorescence 1232:1249 VE-cadherin immunofluorescence 1220:1249 VE-cadherin immunofluorescence 1220:1249 Sialidase treatment of whole cells caused a change of VE-cadherin immunofluorescence from a continuous and netlike superstructural organization to a scattered inconsistent one. 10460833 5 71 theme arteries 931:938 arg1 cells 906:910 endothelial cells 894:910 endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers 894:982 Immunohistochemical labeling of VE-cadherin and sialic acids displayed a codistribution along the intercellular junctions in endothelial cells of human umbilical arteries, veins, and cultured endothelial monolayers. 10460833 7 72 theme whole 1189:1193 arg1 cells 1195:1199 whole cells 1189:1199 whole cells 1189:1199 Sialidase treatment of whole cells caused a change of VE-cadherin immunofluorescence from a continuous and netlike superstructural organization to a scattered inconsistent one. 10460833 7 73 theme scattered 1315:1323 arg1 one 1338:1340 a scattered inconsistent one 1313:1340 a scattered inconsistent one 1313:1340 Sialidase treatment of whole cells caused a change of VE-cadherin immunofluorescence from a continuous and netlike superstructural organization to a scattered inconsistent one. 21133381 1 0 theme milk 159:162 arg1 oligosaccharides 164:179 human milk oligosaccharides 153:179 human milk oligosaccharides 153:179 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 8 1 theme accurate 1099:1106 arg1 masses 1108:1113 accurate masses 1099:1113 accurate masses 1099:1113 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. 21133381 5 2 theme excellent 744:752 arg1 separation 761:770 excellent isomer separation 744:770 excellent isomer separation 744:770 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 5 3 theme isomer 754:759 arg1 separation 761:770 excellent isomer separation 744:770 excellent isomer separation 744:770 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 1 4 theme oligosaccharides 164:179 arg1 oligosaccharides 100:115 Sialylated human milk oligosaccharides 78:115 Sialylated human milk oligosaccharides (SHMOs) 78:123 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 1 4 theme oligosaccharides 164:179 arg1 components 139:148 important components 129:148 important components of human milk oligosaccharides 129:179 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 5 5 theme graphitized 708:718 arg1 PGC 728:730 PGC 728:730 PGC 728:730 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 5 5 theme graphitized 708:718 arg1 carbon 720:725 porous graphitized carbon 701:725 porous graphitized carbon (PGC) 701:731 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 4 6 theme immune 493:498 arg1 response 500:507 the immune response 489:507 the immune response 489:507 It has also been shown that sialic acids are involved in regulating the immune response and aid in brain development. 21133381 3 7 theme hydrophilic 353:363 arg1 nature 365:370 hydrophilic nature 353:370 hydrophilic nature 353:370 Due to their negative charge and hydrophilic nature, they also help modulate cell-cell interactions. 21133381 7 8 theme characteristic 1010:1023 arg1 patterns 1039:1046 characteristic fragmentation patterns 1010:1046 characteristic fragmentation patterns 1010:1046 By applying the proper collision energy, isomers can be readily differentiated by diagnostic peaks and characteristic fragmentation patterns. 21133381 5 9 theme pooled 578:583 arg1 sample 590:595 pooled milk sample 578:595 pooled milk sample 578:595 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 5 10 with SHMOs 776:780 arg1 time 817:820 highly reproducible retention time 787:820 highly reproducible retention time 787:820 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 3 11 theme negative 333:340 arg1 charge 342:347 negative charge 333:347 negative charge 333:347 Due to their negative charge and hydrophilic nature, they also help modulate cell-cell interactions. 21133381 9 12 theme high-throughput 1300:1314 arg1 identification 1342:1355 high-throughput oligosaccharide structure identification 1300:1355 high-throughput oligosaccharide structure identification 1300:1355 When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification. 21133381 5 13 theme milk 585:588 arg1 sample 590:595 pooled milk sample 578:595 pooled milk sample 578:595 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 1 14 theme Sialylated 78:87 arg1 oligosaccharides 100:115 Sialylated human milk oligosaccharides 78:115 Sialylated human milk oligosaccharides (SHMOs) 78:123 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 1 14 theme Sialylated 78:87 arg1 components 139:148 important components 129:148 important components of human milk oligosaccharides 129:179 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 1 14 theme Sialylated 78:87 arg1 SHMOs 118:122 SHMOs 118:122 SHMOs 118:122 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 6 15 theme collision-induced 869:885 arg1 dissociation 887:898 collision-induced dissociation 869:898 collision-induced dissociation (CID) 869:904 The precursor ions were further examined with collision-induced dissociation (CID). 21133381 6 15 theme collision-induced 869:885 arg1 CID 901:903 CID 901:903 CID 901:903 The precursor ions were further examined with collision-induced dissociation (CID). 21133381 0 16 theme sialylated 38:47 arg1 oligosaccharides 60:75 sialylated human milk oligosaccharides 38:75 sialylated human milk oligosaccharides 38:75 Annotation and structural analysis of sialylated human milk oligosaccharides. 21133381 7 17 theme proper 923:928 arg1 energy 940:945 the proper collision energy 919:945 the proper collision energy 919:945 By applying the proper collision energy, isomers can be readily differentiated by diagnostic peaks and characteristic fragmentation patterns. 21133381 1 18 theme human 89:93 arg1 oligosaccharides 100:115 Sialylated human milk oligosaccharides 78:115 Sialylated human milk oligosaccharides (SHMOs) 78:123 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 1 18 theme human 89:93 arg1 components 139:148 important components 129:148 important components of human milk oligosaccharides 129:179 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 1 18 theme human 89:93 arg1 SHMOs 118:122 SHMOs 118:122 SHMOs 118:122 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 8 19 theme HMO 1171:1173 arg1 library 1175:1181 an HMO library 1168:1181 an HMO library 1168:1181 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. 21133381 9 20 theme structure 1332:1340 arg1 identification 1342:1355 high-throughput oligosaccharide structure identification 1300:1355 high-throughput oligosaccharide structure identification 1300:1355 When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification. 21133381 8 21 theme SHMO 1061:1064 arg1 structures 1066:1075 30 SHMO structures 1058:1075 30 SHMO structures with retention times, accurate masses, and MS/MS spectra 1058:1132 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. 21133381 7 22 theme collision 930:938 arg1 energy 940:945 the proper collision energy 919:945 the proper collision energy 919:945 By applying the proper collision energy, isomers can be readily differentiated by diagnostic peaks and characteristic fragmentation patterns. 21133381 1 23 theme milk 95:98 arg1 oligosaccharides 100:115 Sialylated human milk oligosaccharides 78:115 Sialylated human milk oligosaccharides (SHMOs) 78:123 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 1 23 theme milk 95:98 arg1 components 139:148 important components 129:148 important components of human milk oligosaccharides 129:179 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 1 23 theme milk 95:98 arg1 SHMOs 118:122 SHMOs 118:122 SHMOs 118:122 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 9 24 with library 1247:1253 arg1 structures 1268:1277 over 70 structures 1260:1277 over 70 structures 1260:1277 When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification. 21133381 2 25 theme brain 301:305 arg1 development 307:317 neonates' brain development 291:317 neonates' brain development 291:317 Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates' brain development. 21133381 2 26 located found 209:213 arg1 end 234:236 the nonreducing end 218:236 the nonreducing end 218:236 Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates' brain development. 21133381 2 26 located found 209:213 arg2 acids 189:193 Sialic acids 182:193 Sialic acids 182:193 Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates' brain development. 21133381 5 27 theme reproducible 794:805 arg1 time 817:820 highly reproducible retention time 787:820 highly reproducible retention time 787:820 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 5 28 theme enriched 558:565 arg1 SHMOs 567:571 the enriched SHMOs 554:571 the enriched SHMOs from pooled milk sample 554:595 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 0 29 theme structural 15:24 arg1 analysis 26:33 structural analysis 15:33 structural analysis 15:33 Annotation and structural analysis of sialylated human milk oligosaccharides. 21133381 5 30 from sample 590:595 arg1 SHMOs 567:571 the enriched SHMOs 554:571 the enriched SHMOs from pooled milk sample 554:595 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 8 31 theme structures 1066:1075 arg1 structures 1066:1075 30 SHMO structures 1058:1075 30 SHMO structures with retention times, accurate masses, and MS/MS spectra 1058:1132 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. 21133381 8 31 theme structures 1066:1075 arg1 set 1051:1053 A set 1049:1053 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra 1049:1132 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. 21133381 9 32 theme determined 1214:1223 arg1 components 1233:1242 previously determined neutral components 1203:1242 previously determined neutral components 1203:1242 When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification. 21133381 3 33 theme cell-cell 397:405 arg1 interactions 407:418 cell-cell interactions 397:418 cell-cell interactions 397:418 Due to their negative charge and hydrophilic nature, they also help modulate cell-cell interactions. 21133381 9 34 theme neutral 1225:1231 arg1 components 1233:1242 previously determined neutral components 1203:1242 previously determined neutral components 1203:1242 When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification. 21133381 5 35 theme porous 701:706 arg1 PGC 728:730 PGC 728:730 PGC 728:730 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 5 35 theme porous 701:706 arg1 carbon 720:725 porous graphitized carbon 701:725 porous graphitized carbon (PGC) 701:731 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 2 36 theme Sialic 182:187 arg1 acids 189:193 Sialic acids 182:193 Sialic acids 182:193 Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates' brain development. 21133381 0 37 theme milk 55:58 arg1 oligosaccharides 60:75 sialylated human milk oligosaccharides 38:75 sialylated human milk oligosaccharides 38:75 Annotation and structural analysis of sialylated human milk oligosaccharides. 21133381 5 38 theme retention 807:815 arg1 time 817:820 highly reproducible retention time 787:820 highly reproducible retention time 787:820 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 7 39 theme fragmentation 1025:1037 arg1 patterns 1039:1046 characteristic fragmentation patterns 1010:1046 characteristic fragmentation patterns 1010:1046 By applying the proper collision energy, isomers can be readily differentiated by diagnostic peaks and characteristic fragmentation patterns. 21133381 0 40 theme human 49:53 arg1 oligosaccharides 60:75 sialylated human milk oligosaccharides 38:75 sialylated human milk oligosaccharides 38:75 Annotation and structural analysis of sialylated human milk oligosaccharides. 21133381 4 41 theme brain 520:524 arg1 development 526:536 brain development 520:536 brain development 520:536 It has also been shown that sialic acids are involved in regulating the immune response and aid in brain development. 21133381 6 42 theme precursor 827:835 arg1 ions 837:840 The precursor ions 823:840 The precursor ions 823:840 The precursor ions were further examined with collision-induced dissociation (CID). 21133381 2 43 theme nonreducing 222:232 arg1 end 234:236 the nonreducing end 218:236 the nonreducing end 218:236 Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates' brain development. 21133381 7 44 theme diagnostic 989:998 arg1 peaks 1000:1004 diagnostic peaks 989:1004 diagnostic peaks 989:1004 By applying the proper collision energy, isomers can be readily differentiated by diagnostic peaks and characteristic fragmentation patterns. 21133381 4 45 theme sialic 449:454 arg1 acids 456:460 sialic acids 449:460 sialic acids 449:460 It has also been shown that sialic acids are involved in regulating the immune response and aid in brain development. 21133381 9 46 theme oligosaccharide 1316:1330 arg1 identification 1342:1355 high-throughput oligosaccharide structure identification 1300:1355 high-throughput oligosaccharide structure identification 1300:1355 When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification. 21133381 5 47 theme microchip-based 658:672 arg1 column 682:687 a microchip-based nano-LC column 656:687 a microchip-based nano-LC column packed with porous graphitized carbon (PGC) 656:731 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 1 48 theme important 129:137 arg1 oligosaccharides 100:115 Sialylated human milk oligosaccharides 78:115 Sialylated human milk oligosaccharides (SHMOs) 78:123 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 1 48 theme important 129:137 arg1 components 139:148 important components 129:148 important components of human milk oligosaccharides 129:179 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 5 49 theme nano-LC 674:680 arg1 column 682:687 a microchip-based nano-LC column 656:687 a microchip-based nano-LC column packed with porous graphitized carbon (PGC) 656:731 In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. 21133381 0 50 gly sialylated 38:47 arg1 oligosaccharides 60:75 sialylated human milk oligosaccharides 38:75 sialylated human milk oligosaccharides 38:75 Annotation and structural analysis of sialylated human milk oligosaccharides. 21133381 8 51 theme MS/MS 1120:1124 arg1 spectra 1126:1132 MS/MS spectra 1120:1132 MS/MS spectra 1120:1132 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. 21133381 2 52 theme binding 252:258 arg1 sites 260:264 known binding sites 246:264 known binding sites for pathogens 246:278 Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates' brain development. 21133381 8 53 with structures 1066:1075 arg1 spectra 1126:1132 MS/MS spectra 1120:1132 MS/MS spectra 1120:1132 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. 21133381 8 53 with structures 1066:1075 arg1 times 1092:1096 retention times 1082:1096 retention times 1082:1096 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. 21133381 8 53 with structures 1066:1075 arg1 masses 1108:1113 accurate masses 1099:1113 accurate masses 1099:1113 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. 21133381 0 54 theme oligosaccharides 60:75 arg1 Annotation 0:9 Annotation 0:9 Annotation 0:9 Annotation and structural analysis of sialylated human milk oligosaccharides. 21133381 0 54 theme oligosaccharides 60:75 arg1 analysis 26:33 structural analysis 15:33 structural analysis 15:33 Annotation and structural analysis of sialylated human milk oligosaccharides. 21133381 2 55 theme known 246:250 arg1 sites 260:264 known binding sites 246:264 known binding sites for pathogens 246:278 Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates' brain development. 21133381 1 56 theme human 153:157 arg1 oligosaccharides 164:179 human milk oligosaccharides 153:179 human milk oligosaccharides 153:179 Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. 21133381 8 57 theme retention 1082:1090 arg1 times 1092:1096 retention times 1082:1096 retention times 1082:1096 A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. 2318868 5 0 theme monoclonal 875:884 arg1 NS-19-9 896:902 NS-19-9 896:902 NS-19-9 896:902 These two oligosaccharides bound MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but to another sialyl-Le(a) structure-directed monoclonal antibody, NS-19-9, only weakly. 2318868 5 0 theme monoclonal 875:884 arg1 antibody 886:893 another sialyl-Le(a) structure-directed monoclonal antibody 835:893 another sialyl-Le(a) structure-directed monoclonal antibody 835:893 These two oligosaccharides bound MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but to another sialyl-Le(a) structure-directed monoclonal antibody, NS-19-9, only weakly. 2318868 1 1 theme human 137:141 arg1 milk 143:146 human milk 137:146 human milk 137:146 The occurrence of two novel oligosaccharides in human milk was investigated. 2318868 5 2 theme structure-directed 856:873 arg1 NS-19-9 896:902 NS-19-9 896:902 NS-19-9 896:902 These two oligosaccharides bound MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but to another sialyl-Le(a) structure-directed monoclonal antibody, NS-19-9, only weakly. 2318868 5 2 theme structure-directed 856:873 arg1 antibody 886:893 another sialyl-Le(a) structure-directed monoclonal antibody 835:893 another sialyl-Le(a) structure-directed monoclonal antibody 835:893 These two oligosaccharides bound MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but to another sialyl-Le(a) structure-directed monoclonal antibody, NS-19-9, only weakly. 2318868 0 3 theme human 77:81 arg1 milk 83:86 human milk 77:86 human milk 77:86 Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. 2318868 3 4 theme alpha 512:516 arg1 alpha 544:548 Fuc alpha 1----4 540:555 Fuc alpha 1----4 540:555 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 4 theme alpha 512:516 arg1 beta 528:531 NeuAc alpha 2----3Gal beta 1----3 506:538 NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) 506:556 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 4 5 theme oligosaccharides 714:729 arg1 oligosaccharides 714:729 human milk oligosaccharides 703:729 human milk oligosaccharides 703:729 This constitutes the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. 2318868 4 5 theme oligosaccharides 714:729 arg1 residue 692:698 the reducing-end residue 675:698 the reducing-end residue of human milk oligosaccharides 675:729 This constitutes the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. 2318868 2 6 theme antibody 271:278 arg1 column 235:240 a column 233:240 a column of an immobilized monoclonal antibody, MSW 113 233:287 These oligosaccharides were purified by affinity chromatography on a column of an immobilized monoclonal antibody, MSW 113. 2318868 3 7 theme 2----3Gal 518:526 arg1 alpha 544:548 Fuc alpha 1----4 540:555 Fuc alpha 1----4 540:555 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 7 theme 2----3Gal 518:526 arg1 beta 528:531 NeuAc alpha 2----3Gal beta 1----3 506:538 NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) 506:556 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 8 theme 1H 328:329 arg1 spectroscopy 335:346 500-MHz 1H NMR spectroscopy 320:346 500-MHz 1H NMR spectroscopy 320:346 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 2 9 theme monoclonal 260:269 arg1 antibody 271:278 an immobilized monoclonal antibody 245:278 an immobilized monoclonal antibody 245:278 These oligosaccharides were purified by affinity chromatography on a column of an immobilized monoclonal antibody, MSW 113. 2318868 2 9 theme monoclonal 260:269 arg1 MSW 281:283 MSW 113 281:287 MSW 113 281:287 These oligosaccharides were purified by affinity chromatography on a column of an immobilized monoclonal antibody, MSW 113. 2318868 3 10 theme compounds 427:435 arg1 structures 407:416 the structures 403:416 the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal 403:578 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 11 theme NMR 331:333 arg1 spectroscopy 335:346 500-MHz 1H NMR spectroscopy 320:346 500-MHz 1H NMR spectroscopy 320:346 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 2 12 theme immobilized 248:258 arg1 antibody 271:278 an immobilized monoclonal antibody 245:278 an immobilized monoclonal antibody 245:278 These oligosaccharides were purified by affinity chromatography on a column of an immobilized monoclonal antibody, MSW 113. 2318868 2 12 theme immobilized 248:258 arg1 MSW 281:283 MSW 113 281:287 MSW 113 281:287 These oligosaccharides were purified by affinity chromatography on a column of an immobilized monoclonal antibody, MSW 113. 2318868 3 13 theme bombardment-mass 362:377 arg1 spectrometry 379:390 fast atom bombardment-mass spectrometry 352:390 fast atom bombardment-mass spectrometry 352:390 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 4 14 theme milk 709:712 arg1 oligosaccharides 714:729 human milk oligosaccharides 703:729 human milk oligosaccharides 703:729 This constitutes the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. 2318868 2 15 from chromatography 215:228 arg1 column 235:240 a column 233:240 a column of an immobilized monoclonal antibody, MSW 113 233:287 These oligosaccharides were purified by affinity chromatography on a column of an immobilized monoclonal antibody, MSW 113. 2318868 5 16 theme same 787:790 arg1 extent 792:797 nearly the same extent 776:797 nearly the same extent as sialyl-Lea hexasaccharide 776:826 These two oligosaccharides bound MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but to another sialyl-Le(a) structure-directed monoclonal antibody, NS-19-9, only weakly. 2318868 3 17 theme Fuc 540:542 arg1 alpha 544:548 Fuc alpha 1----4 540:555 Fuc alpha 1----4 540:555 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 17 theme Fuc 540:542 arg1 beta 528:531 NeuAc alpha 2----3Gal beta 1----3 506:538 NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) 506:556 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 18 theme fast 352:355 arg1 spectrometry 379:390 fast atom bombardment-mass spectrometry 352:390 fast atom bombardment-mass spectrometry 352:390 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 4 19 theme human 703:707 arg1 oligosaccharides 714:729 human milk oligosaccharides 703:729 human milk oligosaccharides 703:729 This constitutes the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. 2318868 1 20 from occurrence 93:102 arg1 milk 143:146 human milk 137:146 human milk 137:146 The occurrence of two novel oligosaccharides in human milk was investigated. 2318868 5 21 theme sialyl-Lea 802:811 arg1 hexasaccharide 813:826 sialyl-Lea hexasaccharide 802:826 sialyl-Lea hexasaccharide 802:826 These two oligosaccharides bound MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but to another sialyl-Le(a) structure-directed monoclonal antibody, NS-19-9, only weakly. 2318868 0 22 theme tetra- 14:19 arg1 Occurrence 0:9 Occurrence 0:9 Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. 0:87 Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. 2318868 0 23 from structure 64:72 arg1 milk 83:86 human milk 77:86 human milk 77:86 Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. 2318868 4 24 theme galactose 662:670 arg1 occurrence 625:634 the occurrence 621:634 the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides 621:729 This constitutes the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. 2318868 3 25 theme 2----3Gal 455:463 arg1 beta 465:468 2----3Gal beta 1----3 455:475 NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc 443:500 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 0 26 theme pentasaccharides 25:40 arg1 Occurrence 0:9 Occurrence 0:9 Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. 0:87 Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. 2318868 3 27 theme GlcNac 558:563 arg1 beta 565:568 GlcNac beta 558:568 GlcNac beta 558:568 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 28 theme NeuAc 443:447 arg1 alpha 449:453 NeuAc alpha 443:453 NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc 443:500 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 28 theme NeuAc 443:447 arg1 alpha 481:485 Fuc alpha 1----4 477:492 Fuc alpha 1----4 477:492 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 0 29 theme sialyl-Le 51:59 arg1 structure 64:72 the sialyl-Le(a) structure 47:72 the sialyl-Le(a) structure in human milk 47:86 Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. 2318868 0 29 theme sialyl-Le 51:59 arg1 a 61:61 a 61:61 a 61:61 Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. 2318868 2 30 theme affinity 206:213 arg1 chromatography 215:228 affinity chromatography 206:228 affinity chromatography on a column of an immobilized monoclonal antibody, MSW 113 206:287 These oligosaccharides were purified by affinity chromatography on a column of an immobilized monoclonal antibody, MSW 113. 2318868 4 31 theme reducing-end 679:690 arg1 oligosaccharides 714:729 human milk oligosaccharides 703:729 human milk oligosaccharides 703:729 This constitutes the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. 2318868 4 31 theme reducing-end 679:690 arg1 residue 692:698 the reducing-end residue 675:698 the reducing-end residue of human milk oligosaccharides 675:729 This constitutes the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. 2318868 3 32 theme Structural 290:299 arg1 studies 301:307 Structural studies 290:307 Structural studies 290:307 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 33 theme Fuc 477:479 arg1 alpha 449:453 NeuAc alpha 443:453 NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc 443:500 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 33 theme Fuc 477:479 arg1 alpha 481:485 Fuc alpha 1----4 477:492 Fuc alpha 1----4 477:492 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 0 34 with Occurrence 0:9 arg1 structure 64:72 the sialyl-Le(a) structure 47:72 the sialyl-Le(a) structure in human milk 47:86 Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. 2318868 0 34 with Occurrence 0:9 arg1 a 61:61 a 61:61 a 61:61 Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. 2318868 3 35 theme NeuAc 506:510 arg1 alpha 544:548 Fuc alpha 1----4 540:555 Fuc alpha 1----4 540:555 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 35 theme NeuAc 506:510 arg1 beta 528:531 NeuAc alpha 2----3Gal beta 1----3 506:538 NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) 506:556 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 4 36 theme N-acetylglucosamine 639:657 arg1 occurrence 625:634 the occurrence 621:634 the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides 621:729 This constitutes the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. 2318868 4 37 theme first 602:606 arg1 evidence 608:615 the first evidence 598:615 the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides 598:729 This constitutes the first evidence for the occurrence of N-acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. 2318868 3 38 dep alpha 449:453 arg1 beta 465:468 2----3Gal beta 1----3 455:475 NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc 443:500 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 38 dep alpha 449:453 arg1 beta 565:568 GlcNac beta 558:568 GlcNac beta 558:568 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 38 dep alpha 449:453 arg1 GlcNAc 495:500 GlcNAc 495:500 NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc 443:500 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 1 39 theme novel 111:115 arg1 oligosaccharides 117:132 two novel oligosaccharides 107:132 two novel oligosaccharides 107:132 The occurrence of two novel oligosaccharides in human milk was investigated. 2318868 3 40 theme 500-MHz 320:326 arg1 spectroscopy 335:346 500-MHz 1H NMR spectroscopy 320:346 500-MHz 1H NMR spectroscopy 320:346 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 3 41 theme atom 357:360 arg1 spectrometry 379:390 fast atom bombardment-mass spectrometry 352:390 fast atom bombardment-mass spectrometry 352:390 Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. 2318868 1 42 theme oligosaccharides 117:132 arg1 occurrence 93:102 The occurrence 89:102 The occurrence of two novel oligosaccharides in human milk 89:146 The occurrence of two novel oligosaccharides in human milk was investigated. 6703714 0 0 theme anti-oligosaccharide 82:101 arg1 antibodies 103:112 anti-oligosaccharide antibodies 82:112 anti-oligosaccharide antibodies 82:112 A new sialyloligosaccharide from human milk: isolation and characterization using anti-oligosaccharide antibodies. 6703714 2 1 theme H 518:518 arg1 substances 532:541 H blood group substances 518:541 H blood group substances 518:541 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 2 theme Se 612:613 arg1 gene 626:629 the Se (Secretor) gene 608:629 the Se (Secretor) gene 608:629 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 3 theme sequence 423:430 arg1 studies 261:267 Structural studies 250:267 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera 250:375 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 3 theme sequence 423:430 arg1 text 435:438 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 4 dep A 509:509 arg1 consistent 552:561 consistent 552:561 consistent 552:561 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 5 with oligosaccharides 662:677 arg1 1-2Gal 694:699 Fuc alpha 1-2Gal 684:699 Fuc alpha 1-2Gal 684:699 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 6 theme anti-oligosaccharide 351:370 arg1 sera 372:375 specific anti-oligosaccharide sera 342:375 specific anti-oligosaccharide sera 342:375 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 7 theme copy 600:603 arg1 requirement 572:582 the requirement 568:582 the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal 568:699 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 1 8 theme human 185:189 arg1 milk 191:194 human milk 185:194 human milk 185:194 A previously undescribed sialyloligosaccharide has been isolated from human milk using a specific anti-sialyloligosaccharide antibody. 6703714 2 9 with consistent 381:390 arg1 structure 411:419 the following structure 397:419 the following structure 397:419 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 1 10 attach isolated 171:178 arg2 sialyloligosaccharide 140:160 A previously undescribed sialyloligosaccharide 115:160 A previously undescribed sialyloligosaccharide 115:160 A previously undescribed sialyloligosaccharide has been isolated from human milk using a specific anti-sialyloligosaccharide antibody. 6703714 1 10 attach isolated 171:178 arg1 milk 191:194 human milk 185:194 human milk 185:194 A previously undescribed sialyloligosaccharide has been isolated from human milk using a specific anti-sialyloligosaccharide antibody. 6703714 2 11 dep text 435:438 arg1 oligosaccharide 445:459 The oligosaccharide 441:459 The oligosaccharide 441:459 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 11 dep text 435:438 arg1 linkages 707:714 linkages 707:714 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 11 dep text 435:438 arg1 present 464:470 present 464:470 present 464:470 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 0 12 from milk 39:42 arg1 sialyloligosaccharide 6:26 A new sialyloligosaccharide 0:26 A new sialyloligosaccharide from human milk: isolation and characterization using anti-oligosaccharide antibodies. 0:113 A new sialyloligosaccharide from human milk: isolation and characterization using anti-oligosaccharide antibodies. 6703714 2 13 theme Fuc 684:686 arg1 1-2Gal 694:699 Fuc alpha 1-2Gal 684:699 Fuc alpha 1-2Gal 684:699 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 0 14 theme new 2:4 arg1 sialyloligosaccharide 6:26 A new sialyloligosaccharide 0:26 A new sialyloligosaccharide from human milk: isolation and characterization using anti-oligosaccharide antibodies. 0:113 A new sialyloligosaccharide from human milk: isolation and characterization using anti-oligosaccharide antibodies. 6703714 2 15 theme Secretor 616:623 arg1 gene 626:629 the Se (Secretor) gene 608:629 the Se (Secretor) gene 608:629 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 1 16 theme specific 204:211 arg1 antibody 240:247 a specific anti-sialyloligosaccharide antibody 202:247 a specific anti-sialyloligosaccharide antibody 202:247 A previously undescribed sialyloligosaccharide has been isolated from human milk using a specific anti-sialyloligosaccharide antibody. 6703714 2 17 theme oligosaccharides 662:677 arg1 synthesis 649:657 the synthesis 645:657 the synthesis of oligosaccharides with Fuc alpha 1-2Gal 645:699 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 1 18 theme anti-sialyloligosaccharide 213:238 arg1 antibody 240:247 a specific anti-sialyloligosaccharide antibody 202:247 a specific anti-sialyloligosaccharide antibody 202:247 A previously undescribed sialyloligosaccharide has been isolated from human milk using a specific anti-sialyloligosaccharide antibody. 6703714 2 19 theme specific 342:349 arg1 sera 372:375 specific anti-oligosaccharide sera 342:375 specific anti-oligosaccharide sera 342:375 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 20 theme oligosaccharide 289:303 arg1 text 435:438 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 20 theme oligosaccharide 289:303 arg1 studies 261:267 Structural studies 250:267 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera 250:375 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 0 21 theme human 33:37 arg1 milk 39:42 human milk 33:42 human milk 33:42 A new sialyloligosaccharide from human milk: isolation and characterization using anti-oligosaccharide antibodies. 6703714 2 22 attach present 464:470 arg1 milk 480:483 milk 480:483 milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . 480:703 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 22 attach present 464:470 arg2 present 464:470 present 464:470 present 464:470 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 22 attach present 464:470 arg2 oligosaccharide 445:459 The oligosaccharide 441:459 The oligosaccharide 441:459 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 23 theme radiolabeled 276:287 arg1 oligosaccharide 289:303 the radiolabeled oligosaccharide 272:303 the radiolabeled oligosaccharide 272:303 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 1 24 theme undescribed 128:138 arg1 sialyloligosaccharide 140:160 A previously undescribed sialyloligosaccharide 115:160 A previously undescribed sialyloligosaccharide 115:160 A previously undescribed sialyloligosaccharide has been isolated from human milk using a specific anti-sialyloligosaccharide antibody. 6703714 2 25 located present 464:470 arg2 oligosaccharide 445:459 The oligosaccharide 441:459 The oligosaccharide 441:459 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 25 located present 464:470 arg2 present 464:470 present 464:470 present 464:470 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 25 located present 464:470 arg1 milk 480:483 milk 480:483 milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . 480:703 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 26 theme Structural 250:259 arg1 text 435:438 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 26 theme Structural 250:259 arg1 studies 261:267 Structural studies 250:267 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera 250:375 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 27 theme alpha 688:692 arg1 1-2Gal 694:699 Fuc alpha 1-2Gal 684:699 Fuc alpha 1-2Gal 684:699 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 28 theme following 401:409 arg1 structure 411:419 the following structure 397:419 the following structure 397:419 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 29 with consistent 552:561 arg1 requirement 572:582 the requirement 568:582 the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal 568:699 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 0 30 dep sialyloligosaccharide 6:26 arg1 characterization 59:74 characterization 59:74 characterization 59:74 A new sialyloligosaccharide from human milk: isolation and characterization using anti-oligosaccharide antibodies. 6703714 0 30 dep sialyloligosaccharide 6:26 arg1 isolation 45:53 isolation 45:53 isolation 45:53 A new sialyloligosaccharide from human milk: isolation and characterization using anti-oligosaccharide antibodies. 6703714 2 31 dep consistent 381:390 arg1 studies 261:267 Structural studies 250:267 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera 250:375 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 31 dep consistent 381:390 arg1 text 435:438 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 32 theme group 526:530 arg1 substances 532:541 H blood group substances 518:541 H blood group substances 518:541 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 33 theme enzyme 308:313 arg1 degradation 315:325 enzyme degradation 308:325 enzyme degradation 308:325 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 34 from present 464:470 arg1 milk 480:483 milk 480:483 milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . 480:703 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 35 theme blood 520:524 arg1 substances 532:541 H blood group substances 518:541 H blood group substances 518:541 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 36 from donors 490:495 arg1 milk 480:483 milk 480:483 milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . 480:703 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 37 from milk 480:483 arg1 oligosaccharide 445:459 The oligosaccharide 441:459 The oligosaccharide 441:459 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 37 from milk 480:483 arg1 present 464:470 present 464:470 present 464:470 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 38 theme in 432:433 arg1 studies 261:267 Structural studies 250:267 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera 250:375 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 6703714 2 38 theme in 432:433 arg1 text 435:438 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages 422:714 Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages. 4043085 10 0 with reduction 1929:1937 arg1 NaBH4 1944:1948 NaBH4 1944:1948 NaBH4 1944:1948 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H were isolated with high-pressure liquid chromatography after reduction with NaBH4, and subjected to methylation analysis with gas-liquid chromatography--mass spectrometry. 4043085 7 1 theme mannose 1425:1431 arg1 residues 1433:1440 the mannose residues 1421:1440 the mannose residues 1421:1440 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 4 2 theme apolipoprotein-B 644:659 arg1 monosaccharides 625:639 the total monosaccharides 615:639 the total monosaccharides of apolipoprotein-B 615:659 The results indicated that high-mannose glycopeptides interacting strongly with the lectin comprise about 37% of the total monosaccharides of apolipoprotein-B. 4043085 5 3 from serum 926:930 arg1 oligosaccharides 906:921 the total high-mannose oligosaccharides 883:921 the total high-mannose oligosaccharides in serum 883:930 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 5 3 from serum 926:930 arg1 % 878:878 about 10% 870:878 about 10% of the total high-mannose oligosaccharides in serum 870:930 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 2 4 theme only 305:308 arg1 component 318:326 the only protein component 301:326 the only protein component 301:326 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 2 4 theme only 305:308 arg1 apolipoprotein-B 223:238 apolipoprotein-B 223:238 apolipoprotein-B 223:238 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 10 5 theme high-pressure 1887:1899 arg1 chromatography 1908:1921 high-pressure liquid chromatography 1887:1921 high-pressure liquid chromatography 1887:1921 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H were isolated with high-pressure liquid chromatography after reduction with NaBH4, and subjected to methylation analysis with gas-liquid chromatography--mass spectrometry. 4043085 5 6 theme total 687:691 arg1 glycoproteins 699:711 the total serum glycoproteins 683:711 the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides 683:782 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 7 7 contain contains 1345:1352 arg2 structures 1385:1394 five different oligomannosidic structures 1354:1394 five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc 1354:1470 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 7 7 contain contains 1345:1352 arg1 apolipoprotein-B 1328:1343 apolipoprotein-B 1328:1343 apolipoprotein-B 1328:1343 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 7 8 theme different 1359:1367 arg1 structures 1385:1394 five different oligomannosidic structures 1354:1394 five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc 1354:1470 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 8 9 theme polymeric 1596:1604 arg1 structures 1606:1615 the same polymeric structures 1587:1615 the same polymeric structures 1587:1615 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. 4043085 11 10 theme treatment 2100:2108 arg1 results 2074:2080 the results 2070:2080 the results of exoglycosidase treatment 2070:2108 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 11 10 theme treatment 2100:2108 arg1 data 2044:2047 The data 2040:2047 The data of these studies 2040:2064 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 4 11 gly glycopeptides 542:554 arg2 glycopeptides 542:554 high-mannose glycopeptides 529:554 high-mannose glycopeptides interacting strongly with the lectin 529:591 The results indicated that high-mannose glycopeptides interacting strongly with the lectin comprise about 37% of the total monosaccharides of apolipoprotein-B. 4043085 9 12 theme low-density 1689:1699 arg1 lipoproteins 1701:1712 low-density lipoproteins 1689:1712 low-density lipoproteins 1689:1712 Apolipoprotein-B in low-density lipoproteins was calculated to contain five high-mannose chains in total. 4043085 5 13 gly glycoproteins 699:711 arg1 glycoproteins 699:711 the total serum glycoproteins 683:711 the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides 683:782 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 5 14 theme low-density 785:795 arg1 lipoproteins 797:808 low-density lipoproteins 785:808 low-density lipoproteins 785:808 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 6 15 theme biantennary 1018:1028 arg1 rest 937:940 The rest 933:940 The rest of the carbohydrates in low-density lipoproteins 933:989 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 6 15 theme biantennary 1018:1028 arg1 oligosaccharides 1037:1052 mainly biantennary acidic oligosaccharides 1011:1052 mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A 1011:1091 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 5 16 theme monosaccharides 738:752 arg1 monosaccharides 738:752 their monosaccharides 732:752 their monosaccharides 732:752 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 5 16 theme monosaccharides 738:752 arg1 % 727:727 about 5% 720:727 about 5% of their monosaccharides 720:752 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 5 17 gly glycopeptides 770:782 arg2 glycopeptides 770:782 high-mannose glycopeptides 757:782 high-mannose glycopeptides 757:782 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 7 18 dep H. 1251:1252 arg1 indicated 1313:1321 indicated 1313:1321 indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc 1313:1470 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 7 19 theme isolated 1162:1169 arg1 glycopeptides 1171:1183 isolated glycopeptides 1162:1183 isolated glycopeptides 1162:1183 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 5 20 from structures 843:852 arg1 enriched 825:832 enriched 825:832 enriched 825:832 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 7 21 theme oligomannosidic 1098:1112 arg1 chains 1114:1119 The oligomannosidic chains 1094:1119 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides 1094:1183 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 8 22 dep Man9 1648:1651 arg1 Man5 1640:1643 Man5 1640:1643 Man5 1640:1643 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. 4043085 8 23 theme high-mannose 1509:1520 arg1 oligosaccharides 1522:1537 the per-O-benzoylated high-mannose oligosaccharides 1487:1537 the per-O-benzoylated high-mannose oligosaccharides 1487:1537 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. 4043085 11 24 theme studies 2058:2064 arg1 results 2074:2080 the results 2070:2080 the results of exoglycosidase treatment 2070:2108 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 11 24 theme studies 2058:2064 arg1 data 2044:2047 The data 2040:2047 The data of these studies 2040:2064 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 2 25 theme gel 278:280 arg1 electrophoresis 282:296 polyacrylamide gel electrophoresis 263:296 polyacrylamide gel electrophoresis 263:296 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 11 26 dep four 2317:2320 arg1 to 2314:2315 to 2314:2315 to 2314:2315 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 3 27 attach liberated 384:392 arg2 Glycopeptides 370:382 Glycopeptides 370:382 Glycopeptides liberated from apolipoprotein-B by pronase 370:425 Glycopeptides liberated from apolipoprotein-B by pronase were fractionated by affinity chromatography on concanavalin-A--Sepharose. 4043085 3 27 attach liberated 384:392 arg1 apolipoprotein-B 399:414 apolipoprotein-B 399:414 apolipoprotein-B 399:414 Glycopeptides liberated from apolipoprotein-B by pronase were fractionated by affinity chromatography on concanavalin-A--Sepharose. 4043085 0 28 theme human 76:80 arg1 plasma 82:87 human plasma 76:87 human plasma 76:87 High-mannose structure of apolipoprotein-B from low-density lipoproteins of human plasma. 4043085 1 29 theme gel 167:169 arg1 filtration 171:180 gel filtration 167:180 gel filtration 167:180 Human plasma low-density lipoproteins were purified by flotation followed by gel filtration. 4043085 8 30 theme liquid 1556:1561 arg1 chromatography 1563:1576 high-pressure liquid chromatography 1542:1576 high-pressure liquid chromatography 1542:1576 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. 4043085 6 31 theme concanavalin 1078:1089 arg1 A 1091:1091 concanavalin A 1078:1091 concanavalin A 1078:1091 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 0 32 from lipoproteins 60:71 arg1 structure 13:21 High-mannose structure 0:21 High-mannose structure of apolipoprotein-B from low-density lipoproteins of human plasma. 0:88 High-mannose structure of apolipoprotein-B from low-density lipoproteins of human plasma. 4043085 8 33 theme same 1591:1594 arg1 structures 1606:1615 the same polymeric structures 1587:1615 the same polymeric structures 1587:1615 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. 4043085 11 34 theme higher 2209:2214 arg1 structures 2226:2235 (formula: see text) The higher polymeric structures 2185:2235 (formula: see text) The higher polymeric structures 2185:2235 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 5 35 from % 878:878 arg1 serum 926:930 serum 926:930 serum 926:930 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 1 36 theme Human 90:94 arg1 lipoproteins 115:126 Human plasma low-density lipoproteins 90:126 Human plasma low-density lipoproteins 90:126 Human plasma low-density lipoproteins were purified by flotation followed by gel filtration. 4043085 3 37 theme affinity 448:455 arg1 chromatography 457:470 affinity chromatography 448:470 affinity chromatography on concanavalin-A--Sepharose 448:499 Glycopeptides liberated from apolipoprotein-B by pronase were fractionated by affinity chromatography on concanavalin-A--Sepharose. 4043085 0 38 theme High-mannose 0:11 arg1 structure 13:21 High-mannose structure 0:21 High-mannose structure of apolipoprotein-B from low-density lipoproteins of human plasma. 0:88 High-mannose structure of apolipoprotein-B from low-density lipoproteins of human plasma. 4043085 1 39 theme low-density 103:113 arg1 lipoproteins 115:126 Human plasma low-density lipoproteins 90:126 Human plasma low-density lipoproteins 90:126 Human plasma low-density lipoproteins were purified by flotation followed by gel filtration. 4043085 11 40 theme Man5GlcNAc 2273:2282 arg1 structure 2284:2292 the Man5GlcNAc structure 2269:2292 the Man5GlcNAc structure 2269:2292 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 10 41 theme methylation 1968:1978 arg1 analysis 1980:1987 methylation analysis 1968:1987 methylation analysis 1968:1987 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H were isolated with high-pressure liquid chromatography after reduction with NaBH4, and subjected to methylation analysis with gas-liquid chromatography--mass spectrometry. 4043085 5 42 theme total 887:891 arg1 oligosaccharides 906:921 the total high-mannose oligosaccharides 883:921 the total high-mannose oligosaccharides in serum 883:930 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 4 43 theme total 619:623 arg1 monosaccharides 625:639 the total monosaccharides 615:639 the total monosaccharides of apolipoprotein-B 615:659 The results indicated that high-mannose glycopeptides interacting strongly with the lectin comprise about 37% of the total monosaccharides of apolipoprotein-B. 4043085 10 44 theme chromatography--mass 2005:2024 arg1 spectrometry 2026:2037 gas-liquid chromatography--mass spectrometry 1994:2037 gas-liquid chromatography--mass spectrometry 1994:2037 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H were isolated with high-pressure liquid chromatography after reduction with NaBH4, and subjected to methylation analysis with gas-liquid chromatography--mass spectrometry. 4043085 7 45 theme oligosaccharides 1296:1311 arg1 chromatography 1265:1278 Thin-layer chromatography 1254:1278 Thin-layer chromatography of the released oligosaccharides 1254:1311 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 2 46 contain contained 329:337 arg1 moiety 195:200 The protein moiety 183:200 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, 183:327 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 2 46 contain contained 329:337 arg2 % 342:342 4.4% 339:342 4.4% (by weight) carbohydrate 339:367 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 11 47 theme high-mannose 2155:2166 arg1 oligosaccharide 2168:2182 the main high-mannose oligosaccharide 2146:2182 the main high-mannose oligosaccharide 2146:2182 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 7 48 from lipoproteins 1145:1156 arg1 chains 1114:1119 The oligomannosidic chains 1094:1119 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides 1094:1183 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 10 49 theme high-mannose 1789:1800 arg1 oligosaccharides 1802:1817 The different high-mannose oligosaccharides 1775:1817 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H 1775:1866 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H were isolated with high-pressure liquid chromatography after reduction with NaBH4, and subjected to methylation analysis with gas-liquid chromatography--mass spectrometry. 4043085 3 50 from chromatography 457:470 arg1 concanavalin-A--Sepharose 475:499 concanavalin-A--Sepharose 475:499 concanavalin-A--Sepharose 475:499 Glycopeptides liberated from apolipoprotein-B by pronase were fractionated by affinity chromatography on concanavalin-A--Sepharose. 4043085 5 51 contain having 713:718 arg2 % 727:727 about 5% 720:727 about 5% of their monosaccharides 720:752 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 5 51 contain having 713:718 arg1 glycoproteins 699:711 the total serum glycoproteins 683:711 the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides 683:782 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 5 51 contain having 713:718 arg2 monosaccharides 738:752 their monosaccharides 732:752 their monosaccharides 732:752 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 7 52 theme residues 1433:1440 arg1 number 1411:1416 the number 1407:1416 the number of the mannose residues 1407:1440 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 6 53 from carbohydrates 949:961 arg1 lipoproteins 978:989 low-density lipoproteins 966:989 low-density lipoproteins 966:989 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 7 54 theme Thin-layer 1254:1263 arg1 chromatography 1265:1278 Thin-layer chromatography 1254:1278 Thin-layer chromatography of the released oligosaccharides 1254:1311 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 2 55 theme protein 310:316 arg1 component 318:326 the only protein component 301:326 the only protein component 301:326 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 2 55 theme protein 310:316 arg1 apolipoprotein-B 223:238 apolipoprotein-B 223:238 apolipoprotein-B 223:238 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 6 56 theme low-density 966:976 arg1 lipoproteins 978:989 low-density lipoproteins 966:989 low-density lipoproteins 966:989 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 6 57 theme carbohydrates 949:961 arg1 rest 937:940 The rest 933:940 The rest of the carbohydrates in low-density lipoproteins 933:989 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 6 57 theme carbohydrates 949:961 arg1 oligosaccharides 1037:1052 mainly biantennary acidic oligosaccharides 1011:1052 mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A 1011:1091 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 5 58 theme serum 693:697 arg1 glycoproteins 699:711 the total serum glycoproteins 683:711 the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides 683:782 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 11 59 theme alpha 2326:2330 arg1 residues 2337:2344 one to four Man(alpha 1-2) residues 2310:2344 one to four Man(alpha 1-2) residues 2310:2344 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 7 60 from glycopeptides 1171:1183 arg1 chains 1114:1119 The oligomannosidic chains 1094:1119 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides 1094:1183 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 11 61 theme following 2122:2130 arg1 structure 2132:2140 the following structure 2118:2140 the following structure for the main high-mannose oligosaccharide 2118:2182 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 5 62 theme high-mannose 757:768 arg1 glycopeptides 770:782 high-mannose glycopeptides 757:782 high-mannose glycopeptides 757:782 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 11 63 theme Man 2322:2324 arg1 residues 2337:2344 one to four Man(alpha 1-2) residues 2310:2344 one to four Man(alpha 1-2) residues 2310:2344 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 5 64 theme high-mannose 893:904 arg1 oligosaccharides 906:921 the total high-mannose oligosaccharides 883:921 the total high-mannose oligosaccharides in serum 883:930 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 8 65 theme 10:2:3:2:3 1657:1666 arg1 ratio 1628:1632 a molar ratio 1620:1632 a molar ratio (from Man5 to Man9) of 10:2:3:2:3 1620:1666 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. 4043085 8 66 theme high-pressure 1542:1554 arg1 chromatography 1563:1576 high-pressure liquid chromatography 1542:1576 high-pressure liquid chromatography 1542:1576 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. 4043085 5 67 from enriched 825:832 arg1 structures 843:852 these structures 837:852 these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum 837:930 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 6 68 theme acidic 1030:1035 arg1 rest 937:940 The rest 933:940 The rest of the carbohydrates in low-density lipoproteins 933:989 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 6 68 theme acidic 1030:1035 arg1 oligosaccharides 1037:1052 mainly biantennary acidic oligosaccharides 1011:1052 mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A 1011:1091 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 10 69 theme liquid 1901:1906 arg1 chromatography 1908:1921 high-pressure liquid chromatography 1887:1921 high-pressure liquid chromatography 1887:1921 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H were isolated with high-pressure liquid chromatography after reduction with NaBH4, and subjected to methylation analysis with gas-liquid chromatography--mass spectrometry. 4043085 11 70 theme main 2150:2153 arg1 oligosaccharide 2168:2182 the main high-mannose oligosaccharide 2146:2182 the main high-mannose oligosaccharide 2146:2182 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 7 71 theme native 1126:1131 arg1 lipoproteins 1145:1156 native low-density lipoproteins 1126:1156 native low-density lipoproteins 1126:1156 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 7 72 theme low-density 1133:1143 arg1 lipoproteins 1145:1156 native low-density lipoproteins 1126:1156 native low-density lipoproteins 1126:1156 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 5 73 from oligosaccharides 906:921 arg1 serum 926:930 serum 926:930 serum 926:930 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 8 74 theme per-O-benzoylated 1491:1507 arg1 oligosaccharides 1522:1537 the per-O-benzoylated high-mannose oligosaccharides 1487:1537 the per-O-benzoylated high-mannose oligosaccharides 1487:1537 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. 4043085 0 75 theme plasma 82:87 arg1 lipoproteins 60:71 low-density lipoproteins 48:71 low-density lipoproteins of human plasma 48:87 High-mannose structure of apolipoprotein-B from low-density lipoproteins of human plasma. 4043085 2 76 theme polyacrylamide 263:276 arg1 electrophoresis 282:296 polyacrylamide gel electrophoresis 263:296 polyacrylamide gel electrophoresis 263:296 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 9 77 theme high-mannose 1745:1756 arg1 chains 1758:1763 five high-mannose chains 1740:1763 five high-mannose chains 1740:1763 Apolipoprotein-B in low-density lipoproteins was calculated to contain five high-mannose chains in total. 4043085 6 78 from rest 937:940 arg1 lipoproteins 978:989 low-density lipoproteins 966:989 low-density lipoproteins 966:989 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 8 79 theme oligosaccharides 1522:1537 arg1 Separation 1473:1482 Separation 1473:1482 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography 1473:1576 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. 4043085 7 80 gly glycopeptides 1171:1183 arg2 glycopeptides 1171:1183 isolated glycopeptides 1162:1183 isolated glycopeptides 1162:1183 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 11 81 theme exoglycosidase 2085:2098 arg1 treatment 2100:2108 exoglycosidase treatment 2085:2108 exoglycosidase treatment 2085:2108 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 4 82 theme high-mannose 529:540 arg1 glycopeptides 542:554 high-mannose glycopeptides 529:554 high-mannose glycopeptides interacting strongly with the lectin 529:591 The results indicated that high-mannose glycopeptides interacting strongly with the lectin comprise about 37% of the total monosaccharides of apolipoprotein-B. 4043085 7 83 theme oligomannosidic 1369:1383 arg1 structures 1385:1394 five different oligomannosidic structures 1354:1394 five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc 1354:1470 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 5 84 theme oligosaccharides 906:921 arg1 oligosaccharides 906:921 the total high-mannose oligosaccharides 883:921 the total high-mannose oligosaccharides in serum 883:930 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 5 84 theme oligosaccharides 906:921 arg1 % 878:878 about 10% 870:878 about 10% of the total high-mannose oligosaccharides in serum 870:930 Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. 4043085 11 85 theme polymeric 2216:2224 arg1 structures 2226:2235 (formula: see text) The higher polymeric structures 2185:2235 (formula: see text) The higher polymeric structures 2185:2235 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 1 86 theme plasma 96:101 arg1 lipoproteins 115:126 Human plasma low-density lipoproteins 90:126 Human plasma low-density lipoproteins 90:126 Human plasma low-density lipoproteins were purified by flotation followed by gel filtration. 4043085 2 87 dep % 342:342 arg1 carbohydrate 356:367 carbohydrate 356:367 4.4% (by weight) carbohydrate 339:367 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 0 88 theme apolipoprotein-B 26:41 arg1 structure 13:21 High-mannose structure 0:21 High-mannose structure of apolipoprotein-B from low-density lipoproteins of human plasma. 0:88 High-mannose structure of apolipoprotein-B from low-density lipoproteins of human plasma. 4043085 11 89 dep see 2195:2197 arg1 formula 2186:2192 formula 2186:2192 formula 2186:2192 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 4 90 theme monosaccharides 625:639 arg1 % 610:610 about 37% 602:610 about 37% of the total monosaccharides of apolipoprotein-B 602:659 The results indicated that high-mannose glycopeptides interacting strongly with the lectin comprise about 37% of the total monosaccharides of apolipoprotein-B. 4043085 4 90 theme monosaccharides 625:639 arg1 monosaccharides 625:639 the total monosaccharides 615:639 the total monosaccharides of apolipoprotein-B 615:659 The results indicated that high-mannose glycopeptides interacting strongly with the lectin comprise about 37% of the total monosaccharides of apolipoprotein-B. 4043085 9 91 contain contain 1732:1738 arg2 chains 1758:1763 five high-mannose chains 1740:1763 five high-mannose chains 1740:1763 Apolipoprotein-B in low-density lipoproteins was calculated to contain five high-mannose chains in total. 4043085 9 91 contain contain 1732:1738 arg1 Apolipoprotein-B 1669:1684 Apolipoprotein-B 1669:1684 Apolipoprotein-B in low-density lipoproteins 1669:1712 Apolipoprotein-B in low-density lipoproteins was calculated to contain five high-mannose chains in total. 4043085 9 91 contain contain 1732:1738 arg2 Apolipoprotein-B 1669:1684 Apolipoprotein-B 1669:1684 Apolipoprotein-B in low-density lipoproteins 1669:1712 Apolipoprotein-B in low-density lipoproteins was calculated to contain five high-mannose chains in total. 4043085 9 91 contain contain 1732:1738 arg1 total 1768:1772 total 1768:1772 total 1768:1772 Apolipoprotein-B in low-density lipoproteins was calculated to contain five high-mannose chains in total. 4043085 0 92 theme low-density 48:58 arg1 lipoproteins 60:71 low-density lipoproteins 48:71 low-density lipoproteins of human plasma 48:87 High-mannose structure of apolipoprotein-B from low-density lipoproteins of human plasma. 4043085 2 93 theme protein 187:193 arg1 moiety 195:200 The protein moiety 183:200 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, 183:327 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 8 94 theme molar 1622:1626 arg1 ratio 1628:1632 a molar ratio 1620:1632 a molar ratio (from Man5 to Man9) of 10:2:3:2:3 1620:1666 Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. 4043085 7 95 theme released 1287:1294 arg1 oligosaccharides 1296:1311 the released oligosaccharides 1283:1311 the released oligosaccharides 1283:1311 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 10 96 theme endo-beta-N-acetylglucosaminidase 1832:1864 arg1 H 1866:1866 endo-beta-N-acetylglucosaminidase H 1832:1866 endo-beta-N-acetylglucosaminidase H 1832:1866 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H were isolated with high-pressure liquid chromatography after reduction with NaBH4, and subjected to methylation analysis with gas-liquid chromatography--mass spectrometry. 4043085 10 97 theme different 1779:1787 arg1 oligosaccharides 1802:1817 The different high-mannose oligosaccharides 1775:1817 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H 1775:1866 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H were isolated with high-pressure liquid chromatography after reduction with NaBH4, and subjected to methylation analysis with gas-liquid chromatography--mass spectrometry. 4043085 7 98 with digestion 1202:1210 arg1 H. 1251:1252 H. 1251:1252 H. 1251:1252 The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N-acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. 4043085 10 99 theme gas-liquid 1994:2003 arg1 spectrometry 2026:2037 gas-liquid chromatography--mass spectrometry 1994:2037 gas-liquid chromatography--mass spectrometry 1994:2037 The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H were isolated with high-pressure liquid chromatography after reduction with NaBH4, and subjected to methylation analysis with gas-liquid chromatography--mass spectrometry. 4043085 11 100 dep structures 2226:2235 arg1 see 2195:2197 see 2195:2197 see text 2195:2202 The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. 4043085 2 101 theme lipoproteins 209:220 arg1 moiety 195:200 The protein moiety 183:200 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, 183:327 The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. 4043085 9 102 from Apolipoprotein-B 1669:1684 arg1 lipoproteins 1701:1712 low-density lipoproteins 1689:1712 low-density lipoproteins 1689:1712 Apolipoprotein-B in low-density lipoproteins was calculated to contain five high-mannose chains in total. 4043085 6 103 from lipoproteins 978:989 arg1 rest 937:940 The rest 933:940 The rest of the carbohydrates in low-density lipoproteins 933:989 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 4043085 6 103 from lipoproteins 978:989 arg1 oligosaccharides 1037:1052 mainly biantennary acidic oligosaccharides 1011:1052 mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A 1011:1091 The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. 81832 3 0 theme column 336:341 arg1 chromatographies 343:358 P-4 column chromatographies 332:358 P-4 column chromatographies 332:358 Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. 81832 3 1 theme chromatographies 343:358 arg1 combination 301:311 a combination 299:311 a combination of Bio-Gel P-2 and P-4 column chromatographies 299:358 Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. 81832 3 1 theme chromatographies 343:358 arg1 chromatography 370:383 paper chromatography 364:383 paper chromatography 364:383 Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. 81832 1 2 from occurrence 57:66 arg1 chains 115:120 serum-type sugar chains 98:120 serum-type sugar chains of glycoproteins 98:137 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 81832 1 3 theme occurrence 57:66 arg1 Evidence 41:48 Evidence 41:48 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 41:138 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 81832 2 4 theme patient 163:169 arg1 Urine 140:144 Urine 140:144 Urine of a fucosidosis patient 140:169 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 5 theme fucosidosis 151:161 arg1 patient 163:169 a fucosidosis patient 149:169 a fucosidosis patient 149:169 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 1 6 theme X-antigenic 71:81 arg1 determinant 83:93 X-antigenic determinant 71:93 X-antigenic determinant 71:93 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 81832 2 7 contain contained 171:179 arg2 oligosaccharides 207:222 fucosyl oligosaccharides 199:222 fucosyl oligosaccharides 199:222 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 7 contain contained 171:179 arg1 Urine 140:144 Urine 140:144 Urine of a fucosidosis patient 140:169 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 7 contain contained 171:179 arg2 amount 189:194 a large amount 181:194 a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides 181:252 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 7 contain contained 171:179 arg2 glycopeptides 240:252 fucose-rich glycopeptides 228:252 fucose-rich glycopeptides 228:252 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 1 8 theme determinant 83:93 arg1 occurrence 57:66 the occurrence 53:66 the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins 53:137 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 81832 3 9 theme major 259:263 arg1 oligosaccharides 265:280 Six major oligosaccharides 255:280 Six major oligosaccharides 255:280 Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. 81832 1 10 from Evidence 41:48 arg1 chains 115:120 serum-type sugar chains 98:120 serum-type sugar chains of glycoproteins 98:137 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 81832 0 11 theme Urinary 0:6 arg1 oligosaccharides 8:23 Urinary oligosaccharides 0:23 Urinary oligosaccharides of fucosidosis. 0:39 Urinary oligosaccharides of fucosidosis. 81832 1 12 theme serum-type 98:107 arg1 chains 115:120 serum-type sugar chains 98:120 serum-type sugar chains of glycoproteins 98:137 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 81832 0 13 theme fucosidosis 28:38 arg1 oligosaccharides 8:23 Urinary oligosaccharides 0:23 Urinary oligosaccharides of fucosidosis. 0:39 Urinary oligosaccharides of fucosidosis. 81832 1 14 gly glycoproteins 125:137 arg1 glycoproteins 125:137 glycoproteins 125:137 glycoproteins 125:137 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 81832 1 15 theme sugar 109:113 arg1 chains 115:120 serum-type sugar chains 98:120 serum-type sugar chains of glycoproteins 98:137 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 81832 2 16 theme large 183:187 arg1 amount 189:194 a large amount 181:194 a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides 181:252 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 16 theme large 183:187 arg1 oligosaccharides 207:222 fucosyl oligosaccharides 199:222 fucosyl oligosaccharides 199:222 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 16 theme large 183:187 arg1 glycopeptides 240:252 fucose-rich glycopeptides 228:252 fucose-rich glycopeptides 228:252 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 17 theme glycopeptides 240:252 arg1 amount 189:194 a large amount 181:194 a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides 181:252 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 17 theme glycopeptides 240:252 arg1 oligosaccharides 207:222 fucosyl oligosaccharides 199:222 fucosyl oligosaccharides 199:222 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 17 theme glycopeptides 240:252 arg1 glycopeptides 240:252 fucose-rich glycopeptides 228:252 fucose-rich glycopeptides 228:252 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 18 gly glycopeptides 240:252 arg2 glycopeptides 240:252 fucose-rich glycopeptides 228:252 fucose-rich glycopeptides 228:252 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 3 19 theme P-4 332:334 arg1 chromatographies 343:358 P-4 column chromatographies 332:358 P-4 column chromatographies 332:358 Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. 81832 2 20 theme fucose-rich 228:238 arg1 glycopeptides 240:252 fucose-rich glycopeptides 228:252 fucose-rich glycopeptides 228:252 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 1 21 theme glycoproteins 125:137 arg1 chains 115:120 serum-type sugar chains 98:120 serum-type sugar chains of glycoproteins 98:137 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 81832 3 22 theme Bio-Gel 316:322 arg1 P-2 324:326 Bio-Gel P-2 316:326 Bio-Gel P-2 316:326 Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. 81832 2 23 theme oligosaccharides 207:222 arg1 amount 189:194 a large amount 181:194 a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides 181:252 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 23 theme oligosaccharides 207:222 arg1 oligosaccharides 207:222 fucosyl oligosaccharides 199:222 fucosyl oligosaccharides 199:222 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 2 23 theme oligosaccharides 207:222 arg1 glycopeptides 240:252 fucose-rich glycopeptides 228:252 fucose-rich glycopeptides 228:252 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 1 24 from chains 115:120 arg1 Evidence 41:48 Evidence 41:48 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 41:138 Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. 81832 3 25 theme P-2 324:326 arg1 combination 301:311 a combination 299:311 a combination of Bio-Gel P-2 and P-4 column chromatographies 299:358 Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. 81832 3 25 theme P-2 324:326 arg1 chromatography 370:383 paper chromatography 364:383 paper chromatography 364:383 Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. 81832 2 26 theme fucosyl 199:205 arg1 oligosaccharides 207:222 fucosyl oligosaccharides 199:222 fucosyl oligosaccharides 199:222 Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. 81832 3 27 theme paper 364:368 arg1 chromatography 370:383 paper chromatography 364:383 paper chromatography 364:383 Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. 1577715 8 0 theme H 1491:1491 arg1 O 1493:1493 these contained blood group H(O) 1463:1494 these contained blood group H(O) 1463:1494 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 7 1 dep mono- 1091:1095 arg1 % 1101:1101 0.4% 1098:1101 0.4% of the total oligosaccharides 1098:1131 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 1 dep mono- 1091:1095 arg1 oligosaccharides 1200:1215 complex type oligosaccharides 1187:1215 complex type oligosaccharides 1187:1215 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 1 dep mono- 1091:1095 arg1 oligosaccharides 1116:1131 the total oligosaccharides 1106:1131 the total oligosaccharides 1106:1131 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 6 2 theme noteworthy 865:874 arg1 finding 876:882 Another noteworthy finding 857:882 Another noteworthy finding which had not been reported previously 857:921 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 6 2 theme noteworthy 865:874 arg1 occurrence 931:940 the occurrence 927:940 the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures 927:1027 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 6 3 theme oligosaccharide 963:977 arg1 chains 979:984 asparagine-linked oligosaccharide chains 945:984 asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures 945:1027 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 9 4 theme blood 1733:1737 arg1 O 1747:1747 O 1747:1747 O 1747:1747 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 9 4 theme blood 1733:1737 arg1 H 1745:1745 blood group H 1733:1745 the blood group H(O) structure 1729:1758 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 8 5 theme O 1493:1493 arg1 % 1458:1458 0.4% 1455:1458 0.4% 1455:1458 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 5 theme O 1493:1493 arg1 % 1442:1442 approximately 13.2% 1424:1442 approximately 13.2% 1424:1442 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 5 theme O 1493:1493 arg1 O 1493:1493 these contained blood group H(O) 1463:1494 these contained blood group H(O) 1463:1494 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 5 theme O 1493:1493 arg1 B 1504:1504 B 1504:1504 B 1504:1504 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 5 theme O 1493:1493 arg1 % 1448:1448 2.2% 1445:1448 2.2% 1445:1448 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 5 theme O 1493:1493 arg1 residue 1412:1418 a bisecting GlcNAc residue 1393:1418 a bisecting GlcNAc residue 1393:1418 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 7 6 theme total 1110:1114 arg1 oligosaccharides 1116:1131 the total oligosaccharides 1106:1131 the total oligosaccharides 1106:1131 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 9 7 theme H 1745:1745 arg1 structure 1750:1758 the blood group H(O) structure 1729:1758 the blood group H(O) structure 1729:1758 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 3 8 theme communis 561:568 arg1 agglutinin 570:579 Ricinus communis agglutinin 120 553:583 Ricinus communis agglutinin 120 553:583 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 1 9 theme structures 132:141 arg1 Occurrence 91:100 Occurrence 91:100 Occurrence of blood group A, B, and H(O) structures 91:141 Occurrence of blood group A, B, and H(O) structures. 1577715 4 10 theme exoglycosidase 696:709 arg1 digestion 711:719 sequential exoglycosidase digestion 685:719 sequential exoglycosidase digestion 685:719 Their structures were investigated by sequential exoglycosidase digestion in conjunction with methylation analysis. 1577715 10 11 theme oligosaccharides 1799:1814 arg1 Occurrence 1761:1770 Occurrence 1761:1770 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures 1761:1850 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 6 12 theme H 1013:1013 arg1 structures 1018:1027 blood group A, B, and H(O) structures 991:1027 blood group A, B, and H(O) structures 991:1027 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 2 13 attach liberated 274:282 arg2 chains 182:187 The asparagine-linked oligosaccharide chains 144:187 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma 144:252 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 2 13 attach liberated 274:282 arg1 moiety 305:310 the polypeptide moiety 289:310 the polypeptide moiety 289:310 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 10 14 theme A 1833:1833 arg1 structures 1841:1850 blood group A and B structures 1821:1850 blood group A and B structures 1821:1850 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 2 15 theme Willebrand 202:211 arg1 vWF 221:223 vWF 221:223 vWF 221:223 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 2 15 theme Willebrand 202:211 arg1 factor 213:218 human von Willebrand factor 192:218 human von Willebrand factor (vWF) purified from pooled plasma 192:252 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 7 16 theme present 1037:1043 arg1 study 1045:1049 the present study 1033:1049 the present study 1033:1049 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 10 17 with oligosaccharides 1799:1814 arg1 structures 1841:1850 blood group A and B structures 1821:1850 blood group A and B structures 1821:1850 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 10 18 from that 2045:2048 arg1 group 2034:2038 a different blood group 2016:2038 a different blood group from that of the patient 2016:2063 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 10 19 theme blood 1821:1825 arg1 A 1833:1833 blood group A 1821:1833 blood group A 1821:1833 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 2 20 theme human 192:196 arg1 vWF 221:223 vWF 221:223 vWF 221:223 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 2 20 theme human 192:196 arg1 factor 213:218 human von Willebrand factor 192:218 human von Willebrand factor (vWF) purified from pooled plasma 192:252 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 6 21 theme group 997:1001 arg1 O 1015:1015 O 1015:1015 O 1015:1015 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 6 21 theme group 997:1001 arg1 A 1003:1003 blood group A 991:1003 blood group A 991:1003 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 9 22 theme complex 1560:1566 arg1 those 1585:1589 those 1585:1589 those 1585:1589 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 9 22 theme complex 1560:1566 arg1 chains 1573:1578 The tri- and tetraantennary complex type chains 1532:1578 The tri- and tetraantennary complex type chains 1532:1578 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 8 23 theme without 1377:1383 arg1 structures 1506:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 23 theme without 1377:1383 arg1 % 1390:1390 70.0% 1386:1390 70.0% 1386:1390 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 10 24 theme antibodies 1988:1997 arg1 production 1974:1983 the production 1970:1983 the production of antibodies against vWF with a different blood group from that of the patient 1970:2063 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 3 25 dep agglutinin 541:550 arg1 agglutinin 605:614 agglutinin I 605:616 agglutinin I 605:616 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 10 26 theme concentrate 1908:1918 arg1 use 1878:1880 the repeated use 1865:1880 the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs 1865:1952 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 10 27 theme blood 2028:2032 arg1 group 2034:2038 a different blood group 2016:2038 a different blood group from that of the patient 2016:2063 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 10 28 theme B 1839:1839 arg1 structures 1841:1850 blood group A and B structures 1821:1850 blood group A and B structures 1821:1850 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 0 29 theme von 68:70 arg1 factor 83:88 human von Willebrand factor 62:88 human von Willebrand factor 62:88 Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. 1577715 3 30 theme Bio-Gel 627:633 arg1 column 639:644 a Bio-Gel P-4 column 625:644 a Bio-Gel P-4 column 625:644 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 1 31 theme H 127:127 arg1 structures 132:141 blood group A, B, and H(O) structures 105:141 blood group A, B, and H(O) structures 105:141 Occurrence of blood group A, B, and H(O) structures. 1577715 0 32 theme factor 83:88 arg1 chains 52:57 the asparagine-linked oligosaccharide chains 14:57 the asparagine-linked oligosaccharide chains of human von Willebrand factor 14:88 Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. 1577715 8 33 theme bisecting 1395:1403 arg1 residue 1412:1418 a bisecting GlcNAc residue 1393:1418 a bisecting GlcNAc residue 1393:1418 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 33 theme bisecting 1395:1403 arg1 O 1493:1493 these contained blood group H(O) 1463:1494 these contained blood group H(O) 1463:1494 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 9 34 theme N-acetyllactosamine 1608:1626 arg1 repeats 1628:1634 N-acetyllactosamine repeats 1608:1634 N-acetyllactosamine repeats 1608:1634 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 8 35 theme residue 1412:1418 arg1 structures 1506:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 35 theme residue 1412:1418 arg1 % 1390:1390 70.0% 1386:1390 70.0% 1386:1390 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 3 36 theme lectin-affinity 434:448 arg1 columns 450:456 lectin-affinity columns 434:456 lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I 434:616 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 0 37 theme chains 52:57 arg1 Structures 0:9 Structures 0:9 Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor 0:88 Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. 1577715 7 38 theme oligosaccharides 1262:1277 arg1 series 1234:1239 a series 1232:1239 a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%) 1232:1299 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 39 theme mannose 1249:1255 arg1 Man6-9GlcNAc2 1280:1292 Man6-9GlcNAc2 1280:1292 Man6-9GlcNAc2 (0.8%) 1280:1299 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 39 theme mannose 1249:1255 arg1 oligosaccharides 1262:1277 high mannose type oligosaccharides 1244:1277 high mannose type oligosaccharides 1244:1277 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 8 40 theme % 1442:1442 arg1 structures 1506:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 40 theme % 1442:1442 arg1 % 1390:1390 70.0% 1386:1390 70.0% 1386:1390 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 41 theme Biantennary 1302:1312 arg1 chains 1343:1348 Biantennary complex type oligosaccharide chains 1302:1348 Biantennary complex type oligosaccharide chains 1302:1348 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 3 42 theme A 474:474 arg1 columns 450:456 lectin-affinity columns 434:456 lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I 434:616 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 10 43 with vWF 2007:2009 arg1 group 2034:2038 a different blood group 2016:2038 a different blood group from that of the patient 2016:2063 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 3 44 theme Ricinus 553:559 arg1 agglutinin 570:579 Ricinus communis agglutinin 120 553:583 Ricinus communis agglutinin 120 553:583 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 1 45 theme group 111:115 arg1 A 117:117 blood group A 105:117 blood group A 105:117 Occurrence of blood group A, B, and H(O) structures. 1577715 8 46 theme type 1322:1325 arg1 chains 1343:1348 Biantennary complex type oligosaccharide chains 1302:1348 Biantennary complex type oligosaccharide chains 1302:1348 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 7 47 contain contain 1083:1089 arg2 tetraantennary 1165:1178 tetraantennary 1165:1178 tetraantennary (2.3%) 1165:1185 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 47 contain contain 1083:1089 arg2 bi- 1135:1137 bi- 1135:1137 bi-(78.2%) 1135:1144 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 47 contain contain 1083:1089 arg1 glycoprotein 1057:1068 this glycoprotein 1052:1068 this glycoprotein 1052:1068 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 47 contain contain 1083:1089 arg2 mono- 1091:1095 mono- 1091:1095 mono- (0.4% of the total oligosaccharides) 1091:1132 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 47 contain contain 1083:1089 arg2 % 1143:1143 78.2% 1139:1143 78.2% 1139:1143 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 47 contain contain 1083:1089 arg2 % 1184:1184 2.3% 1181:1184 2.3% 1181:1184 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 47 contain contain 1083:1089 arg2 % 1157:1157 12.3% 1153:1157 12.3% 1153:1157 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 47 contain contain 1083:1089 arg2 tri- 1147:1150 tri- 1147:1150 tri- (12.3%) 1147:1158 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 6 48 link asparagine-linked 945:961 arg1 chains 979:984 asparagine-linked oligosaccharide chains 945:984 asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures 945:1027 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 0 49 theme oligosaccharide 36:50 arg1 chains 52:57 the asparagine-linked oligosaccharide chains 14:57 the asparagine-linked oligosaccharide chains of human von Willebrand factor 14:88 Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. 1577715 3 50 theme paper 379:383 arg1 electrophoresis 385:399 paper electrophoresis 379:399 paper electrophoresis 379:399 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 5 51 theme oligosaccharide 829:843 arg1 structures 845:854 oligosaccharide structures 829:854 oligosaccharide structures 829:854 The glycoprotein was shown to be unique in its great diversity of oligosaccharide structures. 1577715 8 52 dep % 1370:1370 arg1 structures 1506:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 52 dep % 1370:1370 arg1 % 1390:1390 70.0% 1386:1390 70.0% 1386:1390 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 9 53 theme chains 1673:1678 arg1 chains 1673:1678 the triantennary chains 1656:1678 the triantennary chains without the N-acetyllactosamine repeat 1656:1717 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 9 53 theme chains 1673:1678 arg1 % 1651:1651 about 13.0% 1641:1651 about 13.0% of the triantennary chains without the N-acetyllactosamine repeat 1641:1717 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 3 54 theme Phaseolus 477:485 arg1 erythrophytohemagglutinin 496:520 Phaseolus vulgaris erythrophytohemagglutinin 477:520 Phaseolus vulgaris erythrophytohemagglutinin 477:520 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 3 54 theme Phaseolus 477:485 arg1 A 474:474 concanavalin A 461:474 concanavalin A 461:474 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 10 55 link asparagine-linked 1781:1797 arg1 oligosaccharides 1799:1814 these asparagine-linked oligosaccharides 1775:1814 these asparagine-linked oligosaccharides with blood group A and B structures 1775:1850 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 10 56 theme factor 1885:1890 arg1 concentrate 1908:1918 factor VIII/vWF pooled concentrate 1885:1918 factor VIII/vWF pooled concentrate for the treatment of hemophiliacs 1885:1952 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 2 57 theme asparagine-linked 148:164 arg1 chains 182:187 The asparagine-linked oligosaccharide chains 144:187 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma 144:252 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 8 58 theme A 1497:1497 arg1 structures 1506:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 58 theme A 1497:1497 arg1 % 1390:1390 70.0% 1386:1390 70.0% 1386:1390 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 6 59 theme blood 991:995 arg1 O 1015:1015 O 1015:1015 O 1015:1015 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 6 59 theme blood 991:995 arg1 A 1003:1003 blood group A 991:1003 blood group A 991:1003 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 7 60 theme complex 1187:1193 arg1 oligosaccharides 1200:1215 complex type oligosaccharides 1187:1215 complex type oligosaccharides 1187:1215 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 8 61 theme contained 1469:1477 arg1 O 1493:1493 these contained blood group H(O) 1463:1494 these contained blood group H(O) 1463:1494 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 7 62 theme oligosaccharides 1116:1131 arg1 % 1101:1101 0.4% 1098:1101 0.4% of the total oligosaccharides 1098:1131 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 62 theme oligosaccharides 1116:1131 arg1 oligosaccharides 1116:1131 the total oligosaccharides 1106:1131 the total oligosaccharides 1106:1131 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 6 63 theme chains 979:984 arg1 finding 876:882 Another noteworthy finding 857:882 Another noteworthy finding which had not been reported previously 857:921 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 6 63 theme chains 979:984 arg1 occurrence 931:940 the occurrence 927:940 the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures 927:1027 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 0 64 link asparagine-linked 18:34 arg1 chains 52:57 the asparagine-linked oligosaccharide chains 14:57 the asparagine-linked oligosaccharide chains of human von Willebrand factor 14:88 Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. 1577715 8 65 theme group 1485:1489 arg1 O 1493:1493 these contained blood group H(O) 1463:1494 these contained blood group H(O) 1463:1494 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 6 66 theme asparagine-linked 945:961 arg1 chains 979:984 asparagine-linked oligosaccharide chains 945:984 asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures 945:1027 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 9 67 theme group 1739:1743 arg1 O 1747:1747 O 1747:1747 O 1747:1747 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 9 67 theme group 1739:1743 arg1 H 1745:1745 blood group H 1733:1745 the blood group H(O) structure 1729:1758 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 4 68 with conjunction 724:734 arg1 analysis 753:760 methylation analysis 741:760 methylation analysis 741:760 Their structures were investigated by sequential exoglycosidase digestion in conjunction with methylation analysis. 1577715 2 69 theme pooled 240:245 arg1 plasma 247:252 pooled plasma 240:252 pooled plasma 240:252 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 10 70 theme hemophiliacs 1941:1952 arg1 treatment 1928:1936 the treatment 1924:1936 the treatment of hemophiliacs 1924:1952 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 3 71 theme Ulex 590:593 arg1 europaeus 595:603 Ulex europaeus 590:603 Ulex europaeus 590:603 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 4 72 theme sequential 685:694 arg1 digestion 711:719 sequential exoglycosidase digestion 685:719 sequential exoglycosidase digestion 685:719 Their structures were investigated by sequential exoglycosidase digestion in conjunction with methylation analysis. 1577715 10 73 theme asparagine-linked 1781:1797 arg1 oligosaccharides 1799:1814 these asparagine-linked oligosaccharides 1775:1814 these asparagine-linked oligosaccharides with blood group A and B structures 1775:1850 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 2 74 theme factor 213:218 arg1 chains 182:187 The asparagine-linked oligosaccharide chains 144:187 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma 144:252 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 10 75 theme pooled 1901:1906 arg1 concentrate 1908:1918 factor VIII/vWF pooled concentrate 1885:1918 factor VIII/vWF pooled concentrate for the treatment of hemophiliacs 1885:1952 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 6 76 theme B 1006:1006 arg1 structures 1018:1027 blood group A, B, and H(O) structures 991:1027 blood group A, B, and H(O) structures 991:1027 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 9 77 theme tri- 1536:1539 arg1 those 1585:1589 those 1585:1589 those 1585:1589 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 9 77 theme tri- 1536:1539 arg1 chains 1573:1578 The tri- and tetraantennary complex type chains 1532:1578 The tri- and tetraantennary complex type chains 1532:1578 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 10 78 theme group 1827:1831 arg1 A 1833:1833 blood group A 1821:1833 blood group A 1821:1833 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 2 79 theme von 198:200 arg1 vWF 221:223 vWF 221:223 vWF 221:223 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 2 79 theme von 198:200 arg1 factor 213:218 human von Willebrand factor 192:218 human von Willebrand factor (vWF) purified from pooled plasma 192:252 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 1 80 theme A 117:117 arg1 structures 132:141 blood group A, B, and H(O) structures 105:141 blood group A, B, and H(O) structures 105:141 Occurrence of blood group A, B, and H(O) structures. 1577715 6 81 theme A 1003:1003 arg1 structures 1018:1027 blood group A, B, and H(O) structures 991:1027 blood group A, B, and H(O) structures 991:1027 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 9 82 theme tetraantennary 1545:1558 arg1 those 1585:1589 those 1585:1589 those 1585:1589 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 9 82 theme tetraantennary 1545:1558 arg1 chains 1573:1578 The tri- and tetraantennary complex type chains 1532:1578 The tri- and tetraantennary complex type chains 1532:1578 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 7 83 gly glycoprotein 1057:1068 arg1 glycoprotein 1057:1068 this glycoprotein 1052:1068 this glycoprotein 1052:1068 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 3 84 theme P-4 635:637 arg1 column 639:644 a Bio-Gel P-4 column 625:644 a Bio-Gel P-4 column 625:644 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 1 85 theme B 120:120 arg1 structures 132:141 blood group A, B, and H(O) structures 105:141 blood group A, B, and H(O) structures 105:141 Occurrence of blood group A, B, and H(O) structures. 1577715 9 86 theme type 1568:1571 arg1 those 1585:1589 those 1585:1589 those 1585:1589 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 9 86 theme type 1568:1571 arg1 chains 1573:1578 The tri- and tetraantennary complex type chains 1532:1578 The tri- and tetraantennary complex type chains 1532:1578 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 0 87 theme Willebrand 72:81 arg1 factor 83:88 human von Willebrand factor 62:88 human von Willebrand factor 62:88 Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. 1577715 5 88 from unique 796:801 arg1 diversity 816:824 its great diversity 806:824 its great diversity of oligosaccharide structures 806:854 The glycoprotein was shown to be unique in its great diversity of oligosaccharide structures. 1577715 10 89 theme different 2018:2026 arg1 group 2034:2038 a different blood group 2016:2038 a different blood group from that of the patient 2016:2063 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 8 90 theme GlcNAc 1405:1410 arg1 residue 1412:1418 a bisecting GlcNAc residue 1393:1418 a bisecting GlcNAc residue 1393:1418 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 90 theme GlcNAc 1405:1410 arg1 O 1493:1493 these contained blood group H(O) 1463:1494 these contained blood group H(O) 1463:1494 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 9 91 contain contained 1719:1727 arg2 structure 1750:1758 the blood group H(O) structure 1729:1758 the blood group H(O) structure 1729:1758 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 9 91 contain contained 1719:1727 arg1 chains 1673:1678 the triantennary chains 1656:1678 the triantennary chains without the N-acetyllactosamine repeat 1656:1717 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 9 91 contain contained 1719:1727 arg1 % 1651:1651 about 13.0% 1641:1651 about 13.0% of the triantennary chains without the N-acetyllactosamine repeat 1641:1717 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 10 92 theme repeated 1869:1876 arg1 use 1878:1880 the repeated use 1865:1880 the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs 1865:1952 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 5 93 from diversity 816:824 arg1 unique 796:801 unique 796:801 unique 796:801 The glycoprotein was shown to be unique in its great diversity of oligosaccharide structures. 1577715 5 93 from diversity 816:824 arg1 glycoprotein 767:778 The glycoprotein 763:778 The glycoprotein 763:778 The glycoprotein was shown to be unique in its great diversity of oligosaccharide structures. 1577715 2 94 theme polypeptide 293:303 arg1 moiety 305:310 the polypeptide moiety 289:310 the polypeptide moiety 289:310 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 7 95 theme type 1257:1260 arg1 Man6-9GlcNAc2 1280:1292 Man6-9GlcNAc2 1280:1292 Man6-9GlcNAc2 (0.8%) 1280:1299 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 95 theme type 1257:1260 arg1 oligosaccharides 1262:1277 high mannose type oligosaccharides 1244:1277 high mannose type oligosaccharides 1244:1277 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 5 96 theme structures 845:854 arg1 diversity 816:824 its great diversity 806:824 its great diversity of oligosaccharide structures 806:854 The glycoprotein was shown to be unique in its great diversity of oligosaccharide structures. 1577715 3 97 dep Datura 523:528 arg1 agglutinin 570:579 Ricinus communis agglutinin 120 553:583 Ricinus communis agglutinin 120 553:583 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 3 97 dep Datura 523:528 arg1 stramonium 530:539 Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I 523:616 Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I 523:616 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 3 97 dep Datura 523:528 arg1 agglutinin 541:550 agglutinin 541:550 agglutinin 541:550 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 3 97 dep Datura 523:528 arg1 europaeus 595:603 Ulex europaeus 590:603 Ulex europaeus 590:603 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 7 98 theme high 1244:1247 arg1 Man6-9GlcNAc2 1280:1292 Man6-9GlcNAc2 1280:1292 Man6-9GlcNAc2 (0.8%) 1280:1299 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 7 98 theme high 1244:1247 arg1 oligosaccharides 1262:1277 high mannose type oligosaccharides 1244:1277 high mannose type oligosaccharides 1244:1277 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 5 99 gly glycoprotein 767:778 arg1 unique 796:801 unique 796:801 unique 796:801 The glycoprotein was shown to be unique in its great diversity of oligosaccharide structures. 1577715 5 99 gly glycoprotein 767:778 arg1 glycoprotein 767:778 The glycoprotein 763:778 The glycoprotein 763:778 The glycoprotein was shown to be unique in its great diversity of oligosaccharide structures. 1577715 0 100 theme asparagine-linked 18:34 arg1 chains 52:57 the asparagine-linked oligosaccharide chains 14:57 the asparagine-linked oligosaccharide chains of human von Willebrand factor 14:88 Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. 1577715 1 101 theme blood 105:109 arg1 A 117:117 blood group A 105:117 blood group A 105:117 Occurrence of blood group A, B, and H(O) structures. 1577715 2 102 link asparagine-linked 148:164 arg1 chains 182:187 The asparagine-linked oligosaccharide chains 144:187 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma 144:252 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 5 103 theme great 810:814 arg1 diversity 816:824 its great diversity 806:824 its great diversity of oligosaccharide structures 806:854 The glycoprotein was shown to be unique in its great diversity of oligosaccharide structures. 1577715 3 104 theme sequential 405:414 arg1 chromatography 416:429 sequential chromatography 405:429 sequential chromatography 405:429 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 8 105 theme complex 1314:1320 arg1 chains 1343:1348 Biantennary complex type oligosaccharide chains 1302:1348 Biantennary complex type oligosaccharide chains 1302:1348 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 3 106 theme concanavalin 461:472 arg1 erythrophytohemagglutinin 496:520 Phaseolus vulgaris erythrophytohemagglutinin 477:520 Phaseolus vulgaris erythrophytohemagglutinin 477:520 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 3 106 theme concanavalin 461:472 arg1 A 474:474 concanavalin A 461:474 concanavalin A 461:474 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 3 106 theme concanavalin 461:472 arg1 Datura 523:528 Datura 523:528 Datura 523:528 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 0 107 theme human 62:66 arg1 factor 83:88 human von Willebrand factor 62:88 human von Willebrand factor 62:88 Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. 1577715 6 108 with chains 979:984 arg1 structures 1018:1027 blood group A, B, and H(O) structures 991:1027 blood group A, B, and H(O) structures 991:1027 Another noteworthy finding which had not been reported previously was the occurrence of asparagine-linked oligosaccharide chains with blood group A, B, and H(O) structures. 1577715 9 109 theme triantennary 1660:1671 arg1 chains 1673:1678 the triantennary chains 1656:1678 the triantennary chains without the N-acetyllactosamine repeat 1656:1717 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 8 110 theme oligosaccharide 1327:1341 arg1 chains 1343:1348 Biantennary complex type oligosaccharide chains 1302:1348 Biantennary complex type oligosaccharide chains 1302:1348 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 7 111 theme type 1195:1198 arg1 oligosaccharides 1200:1215 complex type oligosaccharides 1187:1215 complex type oligosaccharides 1187:1215 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 10 112 theme VIII/vWF 1892:1899 arg1 concentrate 1908:1918 factor VIII/vWF pooled concentrate 1885:1918 factor VIII/vWF pooled concentrate for the treatment of hemophiliacs 1885:1952 Occurrence of these asparagine-linked oligosaccharides with blood group A and B structures suggest that the repeated use of factor VIII/vWF pooled concentrate for the treatment of hemophiliacs could result in the production of antibodies against vWF with a different blood group from that of the patient, and this development may be pathogenic. 1577715 2 113 theme oligosaccharide 166:180 arg1 chains 182:187 The asparagine-linked oligosaccharide chains 144:187 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma 144:252 The asparagine-linked oligosaccharide chains of human von Willebrand factor (vWF) purified from pooled plasma were quantitatively liberated from the polypeptide moiety by hydrazinolysis. 1577715 3 114 theme vulgaris 487:494 arg1 erythrophytohemagglutinin 496:520 Phaseolus vulgaris erythrophytohemagglutinin 477:520 Phaseolus vulgaris erythrophytohemagglutinin 477:520 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 3 114 theme vulgaris 487:494 arg1 A 474:474 concanavalin A 461:474 concanavalin A 461:474 After N-acetylation, these were fractionated by paper electrophoresis and sequential chromatography on lectin-affinity columns of concanavalin A, Phaseolus vulgaris erythrophytohemagglutinin, Datura stramonium agglutinin, Ricinus communis agglutinin 120, and Ulex europaeus agglutinin I and on a Bio-Gel P-4 column. 1577715 7 115 dep series 1234:1239 arg1 addition 1220:1227 addition 1220:1227 addition 1220:1227 In the present study, this glycoprotein was shown to contain mono- (0.4% of the total oligosaccharides), bi-(78.2%), tri- (12.3%), and tetraantennary (2.3%) complex type oligosaccharides in addition to a series of high mannose type oligosaccharides, Man6-9GlcNAc2 (0.8%). 1577715 9 116 theme N-acetyllactosamine 1692:1710 arg1 repeat 1712:1717 the N-acetyllactosamine repeat 1688:1717 the N-acetyllactosamine repeat 1688:1717 The tri- and tetraantennary complex type chains were those with and without N-acetyllactosamine repeats, and about 13.0% of the triantennary chains without the N-acetyllactosamine repeat contained the blood group H(O) structure. 1577715 8 117 theme blood 1479:1483 arg1 O 1493:1493 these contained blood group H(O) 1463:1494 these contained blood group H(O) 1463:1494 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 118 theme B 1504:1504 arg1 structures 1506:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures 1377:1515 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 8 118 theme B 1504:1504 arg1 % 1390:1390 70.0% 1386:1390 70.0% 1386:1390 Biantennary complex type oligosaccharide chains were those with (8.2%) and without (70.0%) a bisecting GlcNAc residue and approximately 13.2%, 2.2%, and 0.4% of these contained blood group H(O), A, and B structures, respectively. 1577715 4 119 theme methylation 741:751 arg1 analysis 753:760 methylation analysis 741:760 methylation analysis 741:760 Their structures were investigated by sequential exoglycosidase digestion in conjunction with methylation analysis. 29053807 5 0 theme oligosaccharide 664:678 arg1 concentrations 680:693 oligosaccharide concentrations 664:693 oligosaccharide concentrations in human milk 664:707 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 8 1 theme strict 969:974 arg1 criteria 986:993 strict inclusion criteria 969:993 strict inclusion criteria 969:993 The application of strict inclusion criteria resulted in 21 articles selected. 29053807 4 2 theme mean 593:596 arg1 concentrations 598:611 representative and reliable mean concentrations 565:611 representative and reliable mean concentrations 565:611 OBJECTIVE The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. 29053807 9 3 theme mothers 1191:1197 arg1 age 1167:1169 gestational age 1155:1169 gestational age 1155:1169 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 9 3 theme mothers 1191:1197 arg1 status 1181:1186 secretor status 1172:1186 secretor status of mothers 1172:1197 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 9 3 theme mothers 1191:1197 arg1 periods 1222:1228 defined lactation periods 1204:1228 defined lactation periods 1204:1228 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 3 4 from structures 293:302 arg1 milk 347:350 human milk 341:350 human milk 341:350 The structures of more than 100 oligosaccharides in human milk have been elucidated so far. 29053807 8 5 theme criteria 986:993 arg1 application 954:964 The application 950:964 The application of strict inclusion criteria 950:993 The application of strict inclusion criteria resulted in 21 articles selected. 29053807 5 6 theme comprehensive 629:641 arg1 search 654:659 A comprehensive literature search 627:659 A comprehensive literature search on oligosaccharide concentrations in human milk 627:707 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 13 7 theme Worldwide 1632:1640 arg1 analyses 1671:1678 CONCLUSIONS Worldwide interlaboratory quantitative analyses 1620:1678 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples 1620:1704 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 9 8 theme lactation 1212:1220 arg1 periods 1222:1228 defined lactation periods 1204:1228 defined lactation periods 1204:1228 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 14 9 from milk 1953:1956 arg1 quantities 1913:1922 quantities 1913:1922 quantities 1913:1922 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 14 9 from milk 1953:1956 arg1 composition 1897:1907 composition 1897:1907 composition 1897:1907 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 2 10 contain have 192:195 arg2 functions 217:225 numerous beneficial functions 197:225 numerous beneficial functions 197:225 These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. 29053807 2 10 contain have 192:195 arg2 protection 249:258 protection 249:258 protection against infectious diseases 249:286 These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. 29053807 2 10 contain have 192:195 arg1 compounds 167:175 These diverse compounds 153:175 These diverse compounds 153:175 These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. 29053807 9 11 theme DATA 1029:1032 arg1 concentrations 1061:1074 DATA EXTRACTION Oligosaccharide concentrations 1029:1074 DATA EXTRACTION Oligosaccharide concentrations 1029:1074 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 5 12 dep Contents 766:773 arg1 Titles 798:803 Lancet Titles 791:803 Lancet Titles 791:803 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 12 dep Contents 766:773 arg1 Contents 766:773 Current Contents 758:773 Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed 758:823 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 12 dep Contents 766:773 arg1 Search 775:780 Search 775:780 Search 775:780 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 12 dep Contents 766:773 arg1 MEDLINE 806:812 MEDLINE 806:812 MEDLINE 806:812 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 12 dep Contents 766:773 arg1 Embase 783:788 Embase 783:788 Embase 783:788 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 12 dep Contents 766:773 arg1 PubMed 818:823 PubMed 818:823 PubMed 818:823 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 4 13 theme main 434:437 arg1 factors 439:445 the main factors 430:445 the main factors that affect the concentrations of oligosaccharides in human milk 430:510 OBJECTIVE The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. 29053807 12 14 located observed 1610:1617 arg2 variations 1582:1591 large interlaboratory variations 1560:1591 large interlaboratory variations in the data 1560:1603 In addition, large interlaboratory variations in the data were observed. 29053807 12 14 located observed 1610:1617 arg1 addition 1550:1557 addition 1550:1557 addition 1550:1557 In addition, large interlaboratory variations in the data were observed. 29053807 14 15 theme oligosaccharides 1927:1942 arg1 quantities 1913:1922 quantities 1913:1922 quantities 1913:1922 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 14 15 theme oligosaccharides 1927:1942 arg1 composition 1897:1907 composition 1897:1907 composition 1897:1907 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 1 16 theme solid 122:126 arg1 component 128:136 the third largest solid component 104:136 the third largest solid component in human milk 104:150 CONTEXT Oligosaccharides are the third largest solid component in human milk. 29053807 1 16 theme solid 122:126 arg1 Oligosaccharides 83:98 CONTEXT Oligosaccharides 75:98 CONTEXT Oligosaccharides 75:98 CONTEXT Oligosaccharides are the third largest solid component in human milk. 29053807 10 17 theme Mean 1239:1242 arg1 concentrations 1244:1257 Mean concentrations 1239:1257 Mean concentrations 1239:1257 RESULTS Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. 29053807 10 17 theme Mean 1239:1242 arg1 limits 1281:1286 confidence limits 1270:1286 confidence limits 1270:1286 RESULTS Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. 29053807 3 18 theme human 341:345 arg1 milk 347:350 human milk 341:350 human milk 341:350 The structures of more than 100 oligosaccharides in human milk have been elucidated so far. 29053807 11 19 theme lactation 1493:1501 arg1 period 1503:1508 the lactation period 1489:1508 the lactation period 1489:1508 Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. 29053807 0 20 theme human 63:67 arg1 milk 69:72 human milk 63:72 human milk 63:72 Systematic review of the concentrations of oligosaccharides in human milk. 29053807 11 21 from Concentrations 1361:1374 arg1 milk 1405:1408 human milk 1399:1408 human milk 1399:1408 Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. 29053807 12 22 theme interlaboratory 1566:1580 arg1 variations 1582:1591 large interlaboratory variations 1560:1591 large interlaboratory variations in the data 1560:1603 In addition, large interlaboratory variations in the data were observed. 29053807 3 23 theme oligosaccharides 321:336 arg1 structures 293:302 The structures 289:302 The structures of more than 100 oligosaccharides in human milk 289:350 The structures of more than 100 oligosaccharides in human milk have been elucidated so far. 29053807 10 24 theme confidence 1270:1279 arg1 limits 1281:1286 confidence limits 1270:1286 confidence limits 1270:1286 RESULTS Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. 29053807 11 25 from oligosaccharides 1379:1394 arg1 milk 1405:1408 human milk 1399:1408 human milk 1399:1408 Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. 29053807 14 26 theme current 1869:1875 arg1 knowledge 1877:1885 the current knowledge 1865:1885 the current knowledge about the composition and quantities of oligosaccharides in human milk 1865:1956 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 13 27 theme reliable 1745:1752 arg1 methods 1754:1760 the most reliable methods 1736:1760 the most reliable methods of determining concentrations of oligosaccharides in human milk 1736:1824 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 11 28 theme variance 1537:1544 arg1 analyses 1525:1532 analyses 1525:1532 analyses of variance 1525:1544 Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. 29053807 9 29 theme mean 1082:1085 arg1 values 1087:1092 mean values 1082:1092 mean values 1082:1092 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 5 30 theme DATA 614:617 arg1 SOURCES 619:625 DATA SOURCES 614:625 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 614:824 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 31 theme Current 758:764 arg1 Contents 766:773 Current Contents 758:773 Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed 758:823 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 31 theme Current 758:764 arg1 databases 739:747 6 electronic databases 726:747 6 electronic databases 726:747 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 31 theme Current 758:764 arg1 Search 775:780 Search 775:780 Search 775:780 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 31 theme Current 758:764 arg1 MEDLINE 806:812 MEDLINE 806:812 MEDLINE 806:812 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 31 theme Current 758:764 arg1 Embase 783:788 Embase 783:788 Embase 783:788 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 31 theme Current 758:764 arg1 PubMed 818:823 PubMed 818:823 PubMed 818:823 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 13 32 from oligosaccharides 1795:1810 arg1 milk 1821:1824 human milk 1815:1824 human milk 1815:1824 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 1 33 from component 128:136 arg1 milk 147:150 human milk 141:150 human milk 141:150 CONTEXT Oligosaccharides are the third largest solid component in human milk. 29053807 1 34 theme CONTEXT 75:81 arg1 component 128:136 the third largest solid component 104:136 the third largest solid component in human milk 104:150 CONTEXT Oligosaccharides are the third largest solid component in human milk. 29053807 1 34 theme CONTEXT 75:81 arg1 Oligosaccharides 83:98 CONTEXT Oligosaccharides 75:98 CONTEXT Oligosaccharides 75:98 CONTEXT Oligosaccharides are the third largest solid component in human milk. 29053807 0 35 theme Systematic 0:9 arg1 review 11:16 Systematic review 0:16 Systematic review of the concentrations of 0:41 Systematic review of the concentrations of oligosaccharides in human milk. 29053807 13 36 theme identical 1683:1691 arg1 samples 1698:1704 identical milk samples 1683:1704 identical milk samples 1683:1704 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 10 37 theme oligosaccharides 1314:1329 arg1 concentrations 1244:1257 Mean concentrations 1239:1257 Mean concentrations 1239:1257 RESULTS Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. 29053807 10 37 theme oligosaccharides 1314:1329 arg1 limits 1281:1286 confidence limits 1270:1286 confidence limits 1270:1286 RESULTS Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. 29053807 1 38 theme third 108:112 arg1 component 128:136 the third largest solid component 104:136 the third largest solid component in human milk 104:150 CONTEXT Oligosaccharides are the third largest solid component in human milk. 29053807 1 38 theme third 108:112 arg1 Oligosaccharides 83:98 CONTEXT Oligosaccharides 75:98 CONTEXT Oligosaccharides 75:98 CONTEXT Oligosaccharides are the third largest solid component in human milk. 29053807 13 39 theme samples 1698:1704 arg1 analyses 1671:1678 CONCLUSIONS Worldwide interlaboratory quantitative analyses 1620:1678 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples 1620:1704 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 9 40 theme Oligosaccharide 1045:1059 arg1 concentrations 1061:1074 DATA EXTRACTION Oligosaccharide concentrations 1029:1074 DATA EXTRACTION Oligosaccharide concentrations 1029:1074 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 0 41 theme concentrations 25:38 arg1 review 11:16 Systematic review 0:16 Systematic review of the concentrations of 0:41 Systematic review of the concentrations of oligosaccharides in human milk. 29053807 5 42 from concentrations 680:693 arg1 milk 704:707 human milk 698:707 human milk 698:707 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 43 theme Lancet 791:796 arg1 Titles 798:803 Lancet Titles 791:803 Lancet Titles 791:803 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 13 44 theme interlaboratory 1642:1656 arg1 analyses 1671:1678 CONCLUSIONS Worldwide interlaboratory quantitative analyses 1620:1678 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples 1620:1704 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 2 45 theme diverse 159:165 arg1 compounds 167:175 These diverse compounds 153:175 These diverse compounds 153:175 These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. 29053807 13 46 from concentrations 1777:1790 arg1 milk 1821:1824 human milk 1815:1824 human milk 1815:1824 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 6 47 theme initial 846:852 arg1 search 854:859 The initial search 842:859 The initial search 842:859 STUDY SELECTION The initial search resulted in 1363 hits. 29053807 14 48 theme functions 2013:2021 arg1 understanding 1981:1993 greater understanding 1973:1993 greater understanding of the biological functions of these compounds 1973:2040 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 2 49 theme numerous 197:204 arg1 protection 249:258 protection 249:258 protection against infectious diseases 249:286 These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. 29053807 2 49 theme numerous 197:204 arg1 functions 217:225 numerous beneficial functions 197:225 numerous beneficial functions 197:225 These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. 29053807 14 50 from composition 1897:1907 arg1 milk 1953:1956 human milk 1947:1956 human milk 1947:1956 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 14 51 from quantities 1913:1922 arg1 milk 1953:1956 human milk 1947:1956 human milk 1947:1956 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 11 52 theme human 1399:1403 arg1 milk 1405:1408 human milk 1399:1408 human milk 1399:1408 Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. 29053807 9 53 theme secretor 1172:1179 arg1 status 1181:1186 secretor status 1172:1186 secretor status of mothers 1172:1197 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 8 54 theme inclusion 976:984 arg1 criteria 986:993 strict inclusion criteria 969:993 strict inclusion criteria 969:993 The application of strict inclusion criteria resulted in 21 articles selected. 29053807 4 55 theme representative 565:578 arg1 concentrations 598:611 representative and reliable mean concentrations 565:611 representative and reliable mean concentrations 565:611 OBJECTIVE The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. 29053807 4 56 theme review 407:412 arg1 aim 395:397 The aim 391:397 The aim of this review 391:412 OBJECTIVE The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. 29053807 4 57 theme reliable 584:591 arg1 concentrations 598:611 representative and reliable mean concentrations 565:611 representative and reliable mean concentrations 565:611 OBJECTIVE The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. 29053807 13 58 theme CONCLUSIONS 1620:1630 arg1 analyses 1671:1678 CONCLUSIONS Worldwide interlaboratory quantitative analyses 1620:1678 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples 1620:1704 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 14 59 theme greater 1973:1979 arg1 understanding 1981:1993 greater understanding 1973:1993 greater understanding of the biological functions of these compounds 1973:2040 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 13 60 theme oligosaccharides 1795:1810 arg1 concentrations 1777:1790 concentrations 1777:1790 concentrations of oligosaccharides in human milk 1777:1824 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 5 61 theme literature 643:652 arg1 search 654:659 A comprehensive literature search 627:659 A comprehensive literature search on oligosaccharide concentrations in human milk 627:707 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 9 62 theme defined 1204:1210 arg1 periods 1222:1228 defined lactation periods 1204:1228 defined lactation periods 1204:1228 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 9 63 dep concentrations 1061:1074 arg1 both 1077:1080 both 1077:1080 both 1077:1080 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 13 64 theme human 1815:1819 arg1 milk 1821:1824 human milk 1815:1824 human milk 1815:1824 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 14 65 from oligosaccharides 1927:1942 arg1 milk 1953:1956 human milk 1947:1956 human milk 1947:1956 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 11 66 theme oligosaccharides 1379:1394 arg1 Concentrations 1361:1374 Concentrations 1361:1374 Concentrations of oligosaccharides in human milk 1361:1408 Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. 29053807 5 67 theme electronic 728:737 arg1 Contents 766:773 Current Contents 758:773 Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed 758:823 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 67 theme electronic 728:737 arg1 databases 739:747 6 electronic databases 726:747 6 electronic databases 726:747 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 5 68 theme human 698:702 arg1 milk 704:707 human milk 698:707 human milk 698:707 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 1 69 theme largest 114:120 arg1 component 128:136 the third largest solid component 104:136 the third largest solid component in human milk 104:150 CONTEXT Oligosaccharides are the third largest solid component in human milk. 29053807 1 69 theme largest 114:120 arg1 Oligosaccharides 83:98 CONTEXT Oligosaccharides 75:98 CONTEXT Oligosaccharides 75:98 CONTEXT Oligosaccharides are the third largest solid component in human milk. 29053807 11 70 from milk 1405:1408 arg1 Concentrations 1361:1374 Concentrations 1361:1374 Concentrations of oligosaccharides in human milk 1361:1408 Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. 29053807 2 71 theme infectious 268:277 arg1 diseases 279:286 infectious diseases 268:286 infectious diseases 268:286 These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. 29053807 12 72 theme large 1560:1564 arg1 variations 1582:1591 large interlaboratory variations 1560:1591 large interlaboratory variations in the data 1560:1603 In addition, large interlaboratory variations in the data were observed. 29053807 9 73 theme EXTRACTION 1034:1043 arg1 concentrations 1061:1074 DATA EXTRACTION Oligosaccharide concentrations 1029:1074 DATA EXTRACTION Oligosaccharide concentrations 1029:1074 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 1 74 theme human 141:145 arg1 milk 147:150 human milk 141:150 human milk 141:150 CONTEXT Oligosaccharides are the third largest solid component in human milk. 29053807 5 75 dep databases 739:747 arg1 BIOSIS 750:755 BIOSIS 750:755 BIOSIS 750:755 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 4 76 theme human 501:505 arg1 milk 507:510 human milk 501:510 human milk 501:510 OBJECTIVE The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. 29053807 12 77 from variations 1582:1591 arg1 data 1600:1603 the data 1596:1603 the data 1596:1603 In addition, large interlaboratory variations in the data were observed. 29053807 10 78 theme neutral 1295:1301 arg1 oligosaccharides 1314:1329 33 neutral and acidic oligosaccharides 1292:1329 33 neutral and acidic oligosaccharides reported 1292:1338 RESULTS Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. 29053807 11 79 theme secretor 1457:1464 arg1 type 1466:1469 the secretor type 1453:1469 the secretor type of the mother 1453:1483 Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. 29053807 14 80 theme human 1947:1951 arg1 milk 1953:1956 human milk 1947:1956 human milk 1947:1956 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 2 81 from functions 217:225 arg1 infants 230:236 infants 230:236 infants 230:236 These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. 29053807 4 82 theme oligosaccharides 481:496 arg1 concentrations 463:476 the concentrations 459:476 the concentrations of oligosaccharides 459:496 OBJECTIVE The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. 29053807 9 83 theme single 1098:1103 arg1 values 1105:1110 single values 1098:1110 single values 1098:1110 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 13 84 from milk 1821:1824 arg1 concentrations 1777:1790 concentrations 1777:1790 concentrations of oligosaccharides in human milk 1777:1824 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 11 85 theme mother 1478:1483 arg1 period 1503:1508 the lactation period 1489:1508 the lactation period 1489:1508 Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. 29053807 11 85 theme mother 1478:1483 arg1 type 1466:1469 the secretor type 1453:1469 the secretor type of the mother 1453:1483 Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. 29053807 5 86 from search 654:659 arg1 concentrations 680:693 oligosaccharide concentrations 664:693 oligosaccharide concentrations in human milk 664:707 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 13 87 theme milk 1693:1696 arg1 samples 1698:1704 identical milk samples 1683:1704 identical milk samples 1683:1704 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 10 88 theme acidic 1307:1312 arg1 oligosaccharides 1314:1329 33 neutral and acidic oligosaccharides 1292:1329 33 neutral and acidic oligosaccharides reported 1292:1338 RESULTS Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. 29053807 14 89 theme compounds 2032:2040 arg1 functions 2013:2021 the biological functions 1998:2021 the biological functions of these compounds 1998:2040 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 6 90 dep resulted 861:868 arg1 SELECTION 832:840 STUDY SELECTION 826:840 STUDY SELECTION 826:840 STUDY SELECTION The initial search resulted in 1363 hits. 29053807 13 91 theme quantitative 1658:1669 arg1 analyses 1671:1678 CONCLUSIONS Worldwide interlaboratory quantitative analyses 1620:1678 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples 1620:1704 CONCLUSIONS Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. 29053807 2 92 theme beneficial 206:215 arg1 protection 249:258 protection 249:258 protection against infectious diseases 249:286 These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. 29053807 2 92 theme beneficial 206:215 arg1 functions 217:225 numerous beneficial functions 197:225 numerous beneficial functions 197:225 These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. 29053807 7 93 theme duplicates 909:918 arg1 elimination 894:904 the elimination 890:904 the elimination of duplicates 890:918 After the elimination of duplicates, the literature was screened. 29053807 10 94 dep RESULTS 1231:1237 arg1 calculated 1349:1358 calculated 1349:1358 could be calculated 1340:1358 RESULTS Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. 29053807 14 95 theme biological 2002:2011 arg1 functions 2013:2021 the biological functions 1998:2021 the biological functions of these compounds 1998:2040 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29053807 4 96 dep OBJECTIVE 381:389 arg1 was 414:416 was 414:416 was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations 414:611 OBJECTIVE The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. 29053807 5 97 dep SOURCES 619:625 arg1 performed 713:721 performed 713:721 was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed 709:823 DATA SOURCES A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. 29053807 9 98 theme gestational 1155:1165 arg1 age 1167:1169 gestational age 1155:1169 gestational age 1155:1169 DATA EXTRACTION Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. 29053807 6 99 theme STUDY 826:830 arg1 SELECTION 832:840 STUDY SELECTION 826:840 STUDY SELECTION 826:840 STUDY SELECTION The initial search resulted in 1363 hits. 29053807 14 100 dep composition 1897:1907 arg1 the 1893:1895 the 1893:1895 the 1893:1895 The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. 29969231 8 0 theme similar 1760:1766 arg1 compounds 1768:1776 similar compounds 1760:1776 similar compounds 1760:1776 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 6 1 theme fragmentation 1316:1328 arg1 techniques 1330:1339 higher energy dissociation (HCD) fragmentation techniques 1283:1339 higher energy dissociation (HCD) fragmentation techniques 1283:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 3 2 theme breastfeeding 521:533 arg1 mothers 535:541 100 breastfeeding mothers 517:541 100 breastfeeding mothers 517:541 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 8 3 theme fluid 1819:1823 arg1 types 1787:1791 other types 1781:1791 other types of milk or any biological fluid containing milk oligosaccharides 1781:1856 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 7 4 theme oligosaccharides 1569:1584 arg1 identification 1548:1561 the identification 1544:1561 the identification of 74 oligosaccharides in the reference material 1544:1610 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 4 5 theme hybrid 854:859 arg1 algorithm 868:876 the newly developed hybrid search algorithm 834:876 the newly developed hybrid search algorithm to elucidate unknown oligosaccharides 834:914 Consensus reference spectra were generated, incorporated into a searchable library, and matched using the newly developed hybrid search algorithm to elucidate unknown oligosaccharides. 29969231 3 6 theme MS 720:721 arg1 Library 723:729 the NIST 17 Tandem MS Library 701:729 the NIST 17 Tandem MS Library 701:729 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 6 7 theme HCD 1311:1313 arg1 techniques 1330:1339 higher energy dissociation (HCD) fragmentation techniques 1283:1339 higher energy dissociation (HCD) fragmentation techniques 1283:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 3 8 from SRM 471:473 arg1 Oligosaccharides 411:426 Oligosaccharides 411:426 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, 411:542 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 2 9 theme consensus 259:267 arg1 spectra 269:275 consensus spectra 259:275 consensus spectra of compounds annotated through various data analysis methods 259:336 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 2 9 theme consensus 259:267 arg1 concept 341:347 a concept 339:347 a concept that can be extended to other varieties of biological fluids 339:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 8 10 theme milk 1836:1839 arg1 oligosaccharides 1841:1856 milk oligosaccharides 1836:1856 milk oligosaccharides 1836:1856 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 7 11 from identification 1548:1561 arg1 material 1603:1610 the reference material 1589:1610 the reference material 1589:1610 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 6 12 theme oligosaccharide 1212:1226 arg1 precursors 1228:1237 various oligosaccharide precursors 1204:1237 various oligosaccharide precursors 1204:1237 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 6 13 theme dissociation 1297:1308 arg1 techniques 1330:1339 higher energy dissociation (HCD) fragmentation techniques 1283:1339 higher energy dissociation (HCD) fragmentation techniques 1283:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 2 14 theme various 308:314 arg1 methods 330:336 various data analysis methods 308:336 various data analysis methods 308:336 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 1 15 theme human 183:187 arg1 milk 189:192 human milk 183:192 human milk 183:192 We report the development and availability of a mass spectral reference library for oligosaccharides in human milk. 29969231 6 16 theme underivatized 1386:1398 arg1 spectra 1446:1452 multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra 1368:1452 multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra 1368:1452 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 6 17 theme energy 1290:1295 arg1 techniques 1330:1339 higher energy dissociation (HCD) fragmentation techniques 1283:1339 higher energy dissociation (HCD) fragmentation techniques 1283:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 6 18 theme free 1377:1380 arg1 spectra 1446:1452 multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra 1368:1452 multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra 1368:1452 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 8 19 dep MS 1693:1694 arg1 reference 1683:1691 reference 1683:1691 reference 1683:1691 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 3 20 theme hydrophilic 584:594 arg1 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 3 20 theme hydrophilic 584:594 arg1 spectrometry 666:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry 584:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) 584:695 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 6 21 with intensities 1189:1199 arg1 Fourier 1244:1250 Fourier 1244:1250 Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques 1244:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 7 22 theme Neutral 1455:1461 arg1 oligosaccharides 1487:1502 Neutral and sialylated isomeric oligosaccharides 1455:1502 Neutral and sialylated isomeric oligosaccharides 1455:1502 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 4 23 theme Consensus 732:740 arg1 spectra 752:758 Consensus reference spectra 732:758 Consensus reference spectra 732:758 Consensus reference spectra were generated, incorporated into a searchable library, and matched using the newly developed hybrid search algorithm to elucidate unknown oligosaccharides. 29969231 3 24 theme electrospray 630:641 arg1 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 3 24 theme electrospray 630:641 arg1 spectrometry 666:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry 584:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) 584:695 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 6 25 theme High 1082:1085 arg1 measurement 1101:1111 High accuracy mass measurement 1082:1111 High accuracy mass measurement for precursor and product ions 1082:1142 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 3 26 theme liquid 608:613 arg1 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 3 26 theme liquid 608:613 arg1 spectrometry 666:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry 584:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) 584:695 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 1 27 theme spectral 132:139 arg1 library 151:157 a mass spectral reference library 125:157 a mass spectral reference library 125:157 We report the development and availability of a mass spectral reference library for oligosaccharides in human milk. 29969231 1 28 theme library 151:157 arg1 availability 109:120 availability 109:120 availability 109:120 We report the development and availability of a mass spectral reference library for oligosaccharides in human milk. 29969231 1 28 theme library 151:157 arg1 development 93:103 development 93:103 development 93:103 We report the development and availability of a mass spectral reference library for oligosaccharides in human milk. 29969231 6 29 theme spectra 1446:1452 arg1 assignment 1354:1363 the assignment 1350:1363 the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra 1350:1452 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 8 30 contain containing 1825:1834 arg1 fluid 1819:1823 any biological fluid 1804:1823 any biological fluid containing milk oligosaccharides 1804:1856 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 8 30 contain containing 1825:1834 arg2 oligosaccharides 1841:1856 milk oligosaccharides 1836:1856 milk oligosaccharides 1836:1856 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 6 31 dep precursor 1117:1125 arg1 ions 1139:1142 ions 1139:1142 ions 1139:1142 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 5 32 theme reference 1030:1038 arg1 standards 1040:1048 reference standards 1030:1048 reference standards 1030:1048 The NIST hybrid search program facilitates the structural assignment of complex oligosaccharides especially when reference standards are not commercially available. 29969231 8 33 theme spectra 1652:1658 arg1 collection 1618:1627 This collection 1613:1627 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides 1613:1732 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 7 34 contain have 1504:1507 arg1 oligosaccharides 1487:1502 Neutral and sialylated isomeric oligosaccharides 1455:1502 Neutral and sialylated isomeric oligosaccharides 1455:1502 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 7 34 contain have 1504:1507 arg2 times 1528:1532 distinct retention times 1509:1532 distinct retention times 1509:1532 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 2 35 theme library 237:243 arg1 variety 217:223 a new variety 211:223 a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids 211:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 2 35 theme library 237:243 arg1 library 237:243 spectral library 228:243 spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids 228:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 3 36 theme Material 461:468 arg1 SRM 471:473 the NIST Standard Reference Material (SRM) 1953 433:479 the NIST Standard Reference Material (SRM) 1953 433:479 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 0 37 theme Mass 11:14 arg1 Library 35:41 a Mass Spectral Reference Library 9:41 a Mass Spectral Reference Library for Oligosaccharides in Human Milk 9:76 Creating a Mass Spectral Reference Library for Oligosaccharides in Human Milk. 29969231 5 38 theme complex 989:995 arg1 oligosaccharides 997:1012 complex oligosaccharides 989:1012 complex oligosaccharides 989:1012 The NIST hybrid search program facilitates the structural assignment of complex oligosaccharides especially when reference standards are not commercially available. 29969231 8 39 theme searchable 1671:1680 arg1 library 1696:1702 a searchable, reference MS library 1669:1702 a searchable, reference MS library of annotated oligosaccharides 1669:1732 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 2 40 theme biological 392:401 arg1 fluids 403:408 biological fluids 392:408 biological fluids 392:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 3 41 theme Standard 442:449 arg1 SRM 471:473 the NIST Standard Reference Material (SRM) 1953 433:479 the NIST Standard Reference Material (SRM) 1953 433:479 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 0 42 theme Reference 25:33 arg1 Library 35:41 a Mass Spectral Reference Library 9:41 a Mass Spectral Reference Library for Oligosaccharides in Human Milk 9:76 Creating a Mass Spectral Reference Library for Oligosaccharides in Human Milk. 29969231 6 43 theme mass 1096:1099 arg1 measurement 1101:1111 High accuracy mass measurement 1082:1111 High accuracy mass measurement for precursor and product ions 1082:1142 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 3 44 theme tandem 654:659 arg1 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 3 44 theme tandem 654:659 arg1 spectrometry 666:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry 584:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) 584:695 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 6 45 with measurement 1101:1111 arg1 Fourier 1244:1250 Fourier 1244:1250 Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques 1244:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 6 46 theme MS/MS 1176:1180 arg1 intensities 1189:1199 the relatively high MS/MS signal intensities 1156:1199 the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques 1156:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 2 47 theme spectral 228:235 arg1 library 237:243 spectral library 228:243 spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids 228:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 8 48 theme annotated 1707:1715 arg1 oligosaccharides 1717:1732 annotated oligosaccharides 1707:1732 annotated oligosaccharides 1707:1732 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 3 49 theme human 494:498 arg1 milk 500:503 human milk pooled 494:510 human milk pooled from 100 breastfeeding mothers 494:541 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 8 50 theme other 1781:1785 arg1 types 1787:1791 other types 1781:1791 other types of milk or any biological fluid containing milk oligosaccharides 1781:1856 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 7 51 theme reference 1593:1601 arg1 material 1603:1610 the reference material 1589:1610 the reference material 1589:1610 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 3 52 theme Tandem 713:718 arg1 Library 723:729 the NIST 17 Tandem MS Library 701:729 the NIST 17 Tandem MS Library 701:729 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 3 53 theme NIST 705:708 arg1 Library 723:729 the NIST 17 Tandem MS Library 701:729 the NIST 17 Tandem MS Library 701:729 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 2 54 theme compounds 280:288 arg1 spectra 269:275 consensus spectra 259:275 consensus spectra of compounds annotated through various data analysis methods 259:336 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 2 54 theme compounds 280:288 arg1 concept 341:347 a concept 339:347 a concept that can be extended to other varieties of biological fluids 339:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 7 55 theme distinct 1509:1516 arg1 times 1528:1532 distinct retention times 1509:1532 distinct retention times 1509:1532 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 4 56 theme unknown 891:897 arg1 oligosaccharides 899:914 unknown oligosaccharides 891:914 unknown oligosaccharides 891:914 Consensus reference spectra were generated, incorporated into a searchable library, and matched using the newly developed hybrid search algorithm to elucidate unknown oligosaccharides. 29969231 5 57 theme NIST 921:924 arg1 program 940:946 The NIST hybrid search program 917:946 The NIST hybrid search program 917:946 The NIST hybrid search program facilitates the structural assignment of complex oligosaccharides especially when reference standards are not commercially available. 29969231 3 58 theme pooled 505:510 arg1 milk 500:503 human milk pooled 494:510 human milk pooled from 100 breastfeeding mothers 494:541 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 8 59 theme biological 1808:1817 arg1 fluid 1819:1823 any biological fluid 1804:1823 any biological fluid containing milk oligosaccharides 1804:1856 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 4 60 theme developed 844:852 arg1 algorithm 868:876 the newly developed hybrid search algorithm 834:876 the newly developed hybrid search algorithm to elucidate unknown oligosaccharides 834:914 Consensus reference spectra were generated, incorporated into a searchable library, and matched using the newly developed hybrid search algorithm to elucidate unknown oligosaccharides. 29969231 6 61 theme precursors 1228:1237 arg1 intensities 1189:1199 the relatively high MS/MS signal intensities 1156:1199 the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques 1156:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 6 61 theme precursors 1228:1237 arg1 measurement 1101:1111 High accuracy mass measurement 1082:1111 High accuracy mass measurement for precursor and product ions 1082:1142 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 2 62 theme data 316:319 arg1 methods 330:336 various data analysis methods 308:336 various data analysis methods 308:336 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 4 63 theme search 861:866 arg1 algorithm 868:876 the newly developed hybrid search algorithm 834:876 the newly developed hybrid search algorithm to elucidate unknown oligosaccharides 834:914 Consensus reference spectra were generated, incorporated into a searchable library, and matched using the newly developed hybrid search algorithm to elucidate unknown oligosaccharides. 29969231 7 64 theme retention 1518:1526 arg1 times 1528:1532 distinct retention times 1509:1532 distinct retention times 1509:1532 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 6 65 theme fucosyllacto- 1400:1412 arg1 spectra 1446:1452 multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra 1368:1452 multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra 1368:1452 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 6 66 theme various 1204:1210 arg1 precursors 1228:1237 various oligosaccharide precursors 1204:1237 various oligosaccharide precursors 1204:1237 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 5 67 theme hybrid 926:931 arg1 program 940:946 The NIST hybrid search program 917:946 The NIST hybrid search program 917:946 The NIST hybrid search program facilitates the structural assignment of complex oligosaccharides especially when reference standards are not commercially available. 29969231 7 68 gly sialylated 1467:1476 arg1 oligosaccharides 1487:1502 Neutral and sialylated isomeric oligosaccharides 1455:1502 Neutral and sialylated isomeric oligosaccharides 1455:1502 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 6 69 theme higher 1283:1288 arg1 techniques 1330:1339 higher energy dissociation (HCD) fragmentation techniques 1283:1339 higher energy dissociation (HCD) fragmentation techniques 1283:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 6 70 dep Fourier 1244:1250 arg1 transform 1252:1260 transform 1252:1260 transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques 1252:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 2 71 theme new 213:215 arg1 variety 217:223 a new variety 211:223 a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids 211:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 2 71 theme new 213:215 arg1 library 237:243 spectral library 228:243 spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids 228:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 5 72 theme search 933:938 arg1 program 940:946 The NIST hybrid search program 917:946 The NIST hybrid search program 917:946 The NIST hybrid search program facilitates the structural assignment of complex oligosaccharides especially when reference standards are not commercially available. 29969231 3 73 from mothers 535:541 arg1 milk 500:503 human milk pooled 494:510 human milk pooled from 100 breastfeeding mothers 494:541 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 8 74 dep searchable 1671:1680 arg1 MS 1693:1694 MS 1693:1694 MS 1693:1694 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 3 75 theme chromatography 615:628 arg1 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 3 75 theme chromatography 615:628 arg1 spectrometry 666:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry 584:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) 584:695 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 6 76 theme accuracy 1087:1094 arg1 measurement 1101:1111 High accuracy mass measurement 1082:1111 High accuracy mass measurement for precursor and product ions 1082:1142 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 0 77 theme Human 67:71 arg1 Milk 73:76 Human Milk 67:76 Human Milk 67:76 Creating a Mass Spectral Reference Library for Oligosaccharides in Human Milk. 29969231 3 78 theme interaction 596:606 arg1 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 3 78 theme interaction 596:606 arg1 spectrometry 666:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry 584:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) 584:695 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 1 79 theme mass 127:130 arg1 library 151:157 a mass spectral reference library 125:157 a mass spectral reference library 125:157 We report the development and availability of a mass spectral reference library for oligosaccharides in human milk. 29969231 6 80 theme ion 1262:1264 arg1 FT-IT 1272:1276 FT-IT 1272:1276 FT-IT 1272:1276 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 6 80 theme ion 1262:1264 arg1 trap 1266:1269 ion trap 1262:1269 ion trap (FT-IT) 1262:1277 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 1 81 dep development 93:103 arg1 the 89:91 the 89:91 the 89:91 We report the development and availability of a mass spectral reference library for oligosaccharides in human milk. 29969231 1 82 from oligosaccharides 163:178 arg1 milk 189:192 human milk 183:192 human milk 183:192 We report the development and availability of a mass spectral reference library for oligosaccharides in human milk. 29969231 1 83 theme reference 141:149 arg1 library 151:157 a mass spectral reference library 125:157 a mass spectral reference library 125:157 We report the development and availability of a mass spectral reference library for oligosaccharides in human milk. 29969231 8 84 theme characterized 1638:1650 arg1 spectra 1652:1658 newly characterized spectra 1632:1658 newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides 1632:1732 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 5 85 theme oligosaccharides 997:1012 arg1 assignment 975:984 the structural assignment 960:984 the structural assignment of complex oligosaccharides 960:1012 The NIST hybrid search program facilitates the structural assignment of complex oligosaccharides especially when reference standards are not commercially available. 29969231 0 86 from Oligosaccharides 47:62 arg1 Milk 73:76 Human Milk 67:76 Human Milk 67:76 Creating a Mass Spectral Reference Library for Oligosaccharides in Human Milk. 29969231 6 87 theme sialyllacto-oligosaccharide 1418:1444 arg1 spectra 1446:1452 multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra 1368:1452 multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra 1368:1452 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 2 88 theme other 373:377 arg1 varieties 379:387 other varieties 373:387 other varieties of biological fluids 373:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 2 88 theme other 373:377 arg1 fluids 403:408 biological fluids 392:408 biological fluids 392:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 5 89 theme structural 964:973 arg1 assignment 975:984 the structural assignment 960:984 the structural assignment of complex oligosaccharides 960:1012 The NIST hybrid search program facilitates the structural assignment of complex oligosaccharides especially when reference standards are not commercially available. 29969231 4 90 theme reference 742:750 arg1 spectra 752:758 Consensus reference spectra 732:758 Consensus reference spectra 732:758 Consensus reference spectra were generated, incorporated into a searchable library, and matched using the newly developed hybrid search algorithm to elucidate unknown oligosaccharides. 29969231 0 91 theme Spectral 16:23 arg1 Library 35:41 a Mass Spectral Reference Library 9:41 a Mass Spectral Reference Library for Oligosaccharides in Human Milk 9:76 Creating a Mass Spectral Reference Library for Oligosaccharides in Human Milk. 29969231 7 92 theme sialylated 1467:1476 arg1 oligosaccharides 1487:1502 Neutral and sialylated isomeric oligosaccharides 1455:1502 Neutral and sialylated isomeric oligosaccharides 1455:1502 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 3 93 theme mass 661:664 arg1 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 3 93 theme mass 661:664 arg1 spectrometry 666:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry 584:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) 584:695 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 2 94 theme fluids 403:408 arg1 varieties 379:387 other varieties 373:387 other varieties of biological fluids 373:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 2 94 theme fluids 403:408 arg1 fluids 403:408 biological fluids 392:408 biological fluids 392:408 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 3 95 theme ionization 643:652 arg1 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 HILIC-ESI-MS/MS 680:694 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 3 95 theme ionization 643:652 arg1 spectrometry 666:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry 584:677 hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) 584:695 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 3 96 theme Reference 451:459 arg1 SRM 471:473 the NIST Standard Reference Material (SRM) 1953 433:479 the NIST Standard Reference Material (SRM) 1953 433:479 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 6 97 theme signal 1182:1187 arg1 intensities 1189:1199 the relatively high MS/MS signal intensities 1156:1199 the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques 1156:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 7 98 theme isomeric 1478:1485 arg1 oligosaccharides 1487:1502 Neutral and sialylated isomeric oligosaccharides 1455:1502 Neutral and sialylated isomeric oligosaccharides 1455:1502 Neutral and sialylated isomeric oligosaccharides have distinct retention times, allowing the identification of 74 oligosaccharides in the reference material. 29969231 6 99 theme high 1171:1174 arg1 intensities 1189:1199 the relatively high MS/MS signal intensities 1156:1199 the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques 1156:1339 High accuracy mass measurement for precursor and product ions, as well as the relatively high MS/MS signal intensities of various oligosaccharide precursors with Fourier transform ion trap (FT-IT) and higher energy dissociation (HCD) fragmentation techniques, enabled the assignment of multiple free and underivatized fucosyllacto- and sialyllacto-oligosaccharide spectra. 29969231 8 100 theme oligosaccharides 1717:1732 arg1 library 1696:1702 a searchable, reference MS library 1669:1702 a searchable, reference MS library of annotated oligosaccharides 1669:1732 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 29969231 4 101 theme searchable 796:805 arg1 library 807:813 a searchable library 794:813 a searchable library 794:813 Consensus reference spectra were generated, incorporated into a searchable library, and matched using the newly developed hybrid search algorithm to elucidate unknown oligosaccharides. 29969231 2 102 theme analysis 321:328 arg1 methods 330:336 various data analysis methods 308:336 various data analysis methods 308:336 This represents a new variety of spectral library that includes consensus spectra of compounds annotated through various data analysis methods, a concept that can be extended to other varieties of biological fluids. 29969231 3 103 theme NIST 437:440 arg1 SRM 471:473 the NIST Standard Reference Material (SRM) 1953 433:479 the NIST Standard Reference Material (SRM) 1953 433:479 Oligosaccharides from the NIST Standard Reference Material (SRM) 1953, composed of human milk pooled from 100 breastfeeding mothers, were identified and characterized using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS) and the NIST 17 Tandem MS Library. 29969231 8 104 theme milk 1796:1799 arg1 types 1787:1791 other types 1781:1791 other types of milk or any biological fluid containing milk oligosaccharides 1781:1856 This collection of newly characterized spectra based on a searchable, reference MS library of annotated oligosaccharides can be applied to analyze similar compounds in other types of milk or any biological fluid containing milk oligosaccharides. 20578730 1 0 theme postnatal 318:326 arg1 development 334:344 postnatal brain development 318:344 postnatal brain development 318:344 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 4 1 theme structural 698:707 arg1 diversity 709:717 the large structural diversity 688:717 the large structural diversity 688:717 Oligosaccharides are produced by competing enzymes that provide the large structural diversity and heterogeneity that characterizes this class of compounds. 20578730 1 2 theme receptor 235:242 arg1 analogues 244:252 receptor analogues 235:252 receptor analogues 235:252 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 6 3 from annotation 931:940 arg1 milk 982:985 milk 982:985 milk 982:985 In this research, annotation of the neutral free oligosaccharides in milk is performed to develop a database for the rapid identification of oligosaccharide structures. 20578730 1 4 theme brain 328:332 arg1 development 334:344 postnatal brain development 318:344 postnatal brain development 318:344 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 9 5 used used 1354:1357 arg2 mass 1342:1345 accurate mass 1333:1345 accurate mass 1333:1345 The reproducible retention time and accurate mass can be used to rapidly identify the OS structures in HMO samples. 20578730 9 5 used used 1354:1357 arg2 time 1324:1327 The reproducible retention time 1297:1327 The reproducible retention time 1297:1327 The reproducible retention time and accurate mass can be used to rapidly identify the OS structures in HMO samples. 20578730 3 6 theme oligosaccharides 497:512 arg1 absorption 446:455 absorption 446:455 absorption 446:455 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 3 6 theme oligosaccharides 497:512 arg1 function 485:492 biological function 474:492 biological function 474:492 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 3 6 theme oligosaccharides 497:512 arg1 catabolism 458:467 catabolism 458:467 catabolism 458:467 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 9 7 from structures 1386:1395 arg1 samples 1404:1410 HMO samples 1400:1410 HMO samples 1400:1410 The reproducible retention time and accurate mass can be used to rapidly identify the OS structures in HMO samples. 20578730 3 8 theme strong 524:529 arg1 correlations 531:542 strong correlations 524:542 strong correlations with their structures 524:564 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 8 9 theme HPLC-Chip/TOF 1213:1225 arg1 MS 1227:1228 HPLC-Chip/TOF MS 1213:1228 HPLC-Chip/TOF MS 1213:1228 HPLC-Chip/TOF MS provides a sensitive and quantitative method for sample profiling. 20578730 7 10 theme mass 1160:1163 arg1 spectrometry 1165:1176 mass spectrometry 1160:1176 mass spectrometry 1160:1176 Our strategy incorporates high performance nanoflow liquid chromatography and mass spectrometry for characterizing HMO structures. 20578730 10 11 theme OS 1439:1440 arg1 structures 1442:1451 45 neutral OS structures 1428:1451 45 neutral OS structures 1428:1451 A library with 45 neutral OS structures has been constructed. 20578730 4 12 theme compounds 770:778 arg1 class 761:765 this class 756:765 this class of compounds 756:778 Oligosaccharides are produced by competing enzymes that provide the large structural diversity and heterogeneity that characterizes this class of compounds. 20578730 7 13 theme liquid 1134:1139 arg1 chromatography 1141:1154 high performance nanoflow liquid chromatography 1108:1154 high performance nanoflow liquid chromatography 1108:1154 Our strategy incorporates high performance nanoflow liquid chromatography and mass spectrometry for characterizing HMO structures. 20578730 10 14 theme neutral 1431:1437 arg1 structures 1442:1451 45 neutral OS structures 1428:1451 45 neutral OS structures 1428:1451 A library with 45 neutral OS structures has been constructed. 20578730 3 15 with correlations 531:542 arg1 structures 555:564 their structures 549:564 their structures 549:564 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 9 16 theme OS 1383:1384 arg1 structures 1386:1395 the OS structures 1379:1395 the OS structures in HMO samples 1379:1410 The reproducible retention time and accurate mass can be used to rapidly identify the OS structures in HMO samples. 20578730 10 17 with library 1415:1421 arg1 structures 1442:1451 45 neutral OS structures 1428:1451 45 neutral OS structures 1428:1451 A library with 45 neutral OS structures has been constructed. 20578730 1 18 theme Human 76:80 arg1 oligosaccharides 87:102 Human milk oligosaccharides 76:102 Human milk oligosaccharides (HMOs) 76:109 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 1 18 theme Human 76:80 arg1 HMOs 105:108 HMOs 105:108 HMOs 105:108 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 7 19 theme performance 1113:1123 arg1 chromatography 1141:1154 high performance nanoflow liquid chromatography 1108:1154 high performance nanoflow liquid chromatography 1108:1154 Our strategy incorporates high performance nanoflow liquid chromatography and mass spectrometry for characterizing HMO structures. 20578730 1 20 theme milk 82:85 arg1 oligosaccharides 87:102 Human milk oligosaccharides 76:102 Human milk oligosaccharides (HMOs) 76:109 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 1 20 theme milk 82:85 arg1 HMOs 105:108 HMOs 105:108 HMOs 105:108 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 8 21 theme sensitive 1241:1249 arg1 method 1268:1273 a sensitive and quantitative method 1239:1273 a sensitive and quantitative method for sample profiling 1239:1294 HPLC-Chip/TOF MS provides a sensitive and quantitative method for sample profiling. 20578730 7 22 theme nanoflow 1125:1132 arg1 chromatography 1141:1154 high performance nanoflow liquid chromatography 1108:1154 high performance nanoflow liquid chromatography 1108:1154 Our strategy incorporates high performance nanoflow liquid chromatography and mass spectrometry for characterizing HMO structures. 20578730 5 23 theme oligosaccharide 885:899 arg1 structures 901:910 oligosaccharide structures 885:910 oligosaccharide structures 885:910 Unlike the proteome, there is no template for oligosaccharides, making it difficult to rapidly identify oligosaccharide structures. 20578730 0 24 theme annotated 18:26 arg1 library 28:34 an annotated library 15:34 an annotated library of neutral human milk oligosaccharides 15:73 Development of an annotated library of neutral human milk oligosaccharides. 20578730 9 25 theme HMO 1400:1402 arg1 samples 1404:1410 HMO samples 1400:1410 HMO samples 1400:1410 The reproducible retention time and accurate mass can be used to rapidly identify the OS structures in HMO samples. 20578730 11 26 theme secretor 1590:1597 arg1 status 1599:1604 the secretor status 1586:1604 the secretor status 1586:1604 The structures include information regarding the epitopes such as Lewis type, as well as information regarding the secretor status. 20578730 2 27 theme human 413:417 arg1 system 426:431 the human immune system 409:431 the human immune system 409:431 There is further evidence that HMOs participate in modulating the human immune system. 20578730 2 28 theme immune 419:424 arg1 system 426:431 the human immune system 409:431 the human immune system 409:431 There is further evidence that HMOs participate in modulating the human immune system. 20578730 1 29 theme pathogens 276:284 arg1 binding 265:271 binding 265:271 binding of pathogens 265:284 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 7 30 theme high 1108:1111 arg1 chromatography 1141:1154 high performance nanoflow liquid chromatography 1108:1154 high performance nanoflow liquid chromatography 1108:1154 Our strategy incorporates high performance nanoflow liquid chromatography and mass spectrometry for characterizing HMO structures. 20578730 4 31 theme large 692:696 arg1 diversity 709:717 the large structural diversity 688:717 the large structural diversity 688:717 Oligosaccharides are produced by competing enzymes that provide the large structural diversity and heterogeneity that characterizes this class of compounds. 20578730 6 32 theme structures 1070:1079 arg1 identification 1036:1049 the rapid identification 1026:1049 the rapid identification of oligosaccharide structures 1026:1079 In this research, annotation of the neutral free oligosaccharides in milk is performed to develop a database for the rapid identification of oligosaccharide structures. 20578730 8 33 theme sample 1279:1284 arg1 profiling 1286:1294 sample profiling 1279:1294 sample profiling 1279:1294 HPLC-Chip/TOF MS provides a sensitive and quantitative method for sample profiling. 20578730 9 34 theme reproducible 1301:1312 arg1 time 1324:1327 The reproducible retention time 1297:1327 The reproducible retention time 1297:1327 The reproducible retention time and accurate mass can be used to rapidly identify the OS structures in HMO samples. 20578730 6 35 theme oligosaccharide 1054:1068 arg1 structures 1070:1079 oligosaccharide structures 1054:1079 oligosaccharide structures 1054:1079 In this research, annotation of the neutral free oligosaccharides in milk is performed to develop a database for the rapid identification of oligosaccharide structures. 20578730 0 36 theme library 28:34 arg1 Development 0:10 Development 0:10 Development of an annotated library of neutral human milk oligosaccharides. 0:74 Development of an annotated library of neutral human milk oligosaccharides. 20578730 3 37 contain have 519:522 arg1 absorption 446:455 absorption 446:455 absorption 446:455 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 3 37 contain have 519:522 arg1 function 485:492 biological function 474:492 biological function 474:492 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 3 37 contain have 519:522 arg2 correlations 531:542 strong correlations 524:542 strong correlations with their structures 524:564 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 3 37 contain have 519:522 arg1 catabolism 458:467 catabolism 458:467 catabolism 458:467 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 9 38 theme retention 1314:1322 arg1 time 1324:1327 The reproducible retention time 1297:1327 The reproducible retention time 1297:1327 The reproducible retention time and accurate mass can be used to rapidly identify the OS structures in HMO samples. 20578730 1 39 theme beneficial 200:209 arg1 bacteria 222:229 beneficial intestinal bacteria 200:229 beneficial intestinal bacteria 200:229 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 0 40 theme human 47:51 arg1 oligosaccharides 58:73 neutral human milk oligosaccharides 39:73 neutral human milk oligosaccharides 39:73 Development of an annotated library of neutral human milk oligosaccharides. 20578730 6 41 theme oligosaccharides 962:977 arg1 annotation 931:940 annotation 931:940 annotation of the neutral free oligosaccharides in milk 931:985 In this research, annotation of the neutral free oligosaccharides in milk is performed to develop a database for the rapid identification of oligosaccharide structures. 20578730 3 42 theme structure 567:575 arg1 elucidation 577:587 structure elucidation 567:587 structure elucidation 567:587 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 3 43 theme biological 474:483 arg1 function 485:492 biological function 474:492 biological function 474:492 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 0 44 theme neutral 39:45 arg1 oligosaccharides 58:73 neutral human milk oligosaccharides 39:73 neutral human milk oligosaccharides 39:73 Development of an annotated library of neutral human milk oligosaccharides. 20578730 6 45 theme neutral 949:955 arg1 oligosaccharides 962:977 the neutral free oligosaccharides 945:977 the neutral free oligosaccharides 945:977 In this research, annotation of the neutral free oligosaccharides in milk is performed to develop a database for the rapid identification of oligosaccharide structures. 20578730 9 46 theme accurate 1333:1340 arg1 mass 1342:1345 accurate mass 1333:1345 accurate mass 1333:1345 The reproducible retention time and accurate mass can be used to rapidly identify the OS structures in HMO samples. 20578730 7 47 theme HMO 1197:1199 arg1 structures 1201:1210 HMO structures 1197:1210 HMO structures 1197:1210 Our strategy incorporates high performance nanoflow liquid chromatography and mass spectrometry for characterizing HMO structures. 20578730 6 48 theme rapid 1030:1034 arg1 identification 1036:1049 the rapid identification 1026:1049 the rapid identification of oligosaccharide structures 1026:1079 In this research, annotation of the neutral free oligosaccharides in milk is performed to develop a database for the rapid identification of oligosaccharide structures. 20578730 1 49 theme intestinal 211:220 arg1 bacteria 222:229 beneficial intestinal bacteria 200:229 beneficial intestinal bacteria 200:229 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 3 50 dep absorption 446:455 arg1 the 442:444 the 442:444 the 442:444 Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. 20578730 11 51 theme Lewis 1541:1545 arg1 type 1547:1550 Lewis type 1541:1550 Lewis type 1541:1550 The structures include information regarding the epitopes such as Lewis type, as well as information regarding the secretor status. 20578730 1 52 theme bacteria 222:229 arg1 growth 190:195 the growth 186:195 the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development 186:344 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 0 53 theme oligosaccharides 58:73 arg1 library 28:34 an annotated library 15:34 an annotated library of neutral human milk oligosaccharides 15:73 Development of an annotated library of neutral human milk oligosaccharides. 20578730 2 54 theme further 356:362 arg1 evidence 364:371 further evidence that HMOs participate in modulating the human immune system 356:431 further evidence that HMOs participate in modulating the human immune system 356:431 There is further evidence that HMOs participate in modulating the human immune system. 20578730 0 55 theme milk 53:56 arg1 oligosaccharides 58:73 neutral human milk oligosaccharides 39:73 neutral human milk oligosaccharides 39:73 Development of an annotated library of neutral human milk oligosaccharides. 20578730 8 56 theme quantitative 1255:1266 arg1 method 1268:1273 a sensitive and quantitative method 1239:1273 a sensitive and quantitative method for sample profiling 1239:1294 HPLC-Chip/TOF MS provides a sensitive and quantitative method for sample profiling. 20578730 1 57 theme functions 131:139 arg1 number 121:126 a number 119:126 a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development 119:344 Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. 20578730 6 58 theme free 957:960 arg1 oligosaccharides 962:977 the neutral free oligosaccharides 945:977 the neutral free oligosaccharides 945:977 In this research, annotation of the neutral free oligosaccharides in milk is performed to develop a database for the rapid identification of oligosaccharide structures. 9740055 7 0 from glycoprotein 1474:1485 arg1 analysis 1428:1435 the analysis 1424:1435 the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog 1424:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 7 0 from glycoprotein 1474:1485 arg1 glycans 1449:1455 N-linked glycans 1440:1455 N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog 1440:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 10 1 theme sugars 1872:1877 arg1 glycans 1821:1827 more triantennary glycans 1803:1827 more triantennary glycans 1803:1827 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 10 1 theme sugars 1872:1877 arg1 amount 1847:1852 a substantial amount 1833:1852 a substantial amount of tetraantennary sugars 1833:1877 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 10 1 theme sugars 1872:1877 arg1 sugars 1872:1877 tetraantennary sugars 1857:1877 tetraantennary sugars 1857:1877 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 1 2 theme N-linked 343:350 arg1 carbohydrates 352:364 N-linked carbohydrates 343:364 N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) 343:533 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 0 3 theme glycoprotein 273:284 arg1 glycosylation 244:256 species-specific glycosylation 227:256 species-specific glycosylation of alpha1-acid glycoprotein 227:284 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 2 4 contain containing 556:565 arg1 bands 550:554 The separated bands 536:554 The separated bands containing the glycoproteins 536:583 The separated bands containing the glycoproteins were cut from the gel, destained, reduced and alkylated. 9740055 2 4 contain containing 556:565 arg2 glycoproteins 571:583 the glycoproteins 567:583 the glycoproteins 567:583 The separated bands containing the glycoproteins were cut from the gel, destained, reduced and alkylated. 9740055 8 5 from differences 1540:1550 arg1 glycosylation 1555:1567 glycosylation 1555:1567 glycosylation 1555:1567 Major species-specific differences in glycosylation were found. 9740055 4 6 theme resins 965:970 arg1 column 942:947 a mixed-bed column 930:947 a mixed-bed column of ion-exchange resins 930:970 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 10 7 theme Biantennary 1709:1719 arg1 glycans 1721:1727 Biantennary glycans 1709:1727 Biantennary glycans 1709:1727 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 10 7 theme Biantennary 1709:1719 arg1 carbohydrates 1750:1762 the predominant carbohydrates 1734:1762 the predominant carbohydrates in cow, sheep and dog 1734:1784 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 3 8 theme N-linked 642:649 arg1 glycans 651:657 N-linked glycans 642:657 N-linked glycans 642:657 N-linked glycans were then released by in-gel incubation with peptide N-glycosidase-F (PNGase-F) and extracted with water and acetonitrile. 9740055 6 9 theme tryptic 1290:1296 arg1 peptides 1298:1305 the tryptic peptides 1286:1305 the tryptic peptides 1286:1305 Following glycan release and extraction, the protein could be digested within the gel with trypsin, and the masses of the tryptic peptides could be compared with those generated from a sequence database for protein identification. 9740055 4 10 theme acid-containing 789:803 arg1 glycans 805:811 Sialic acid-containing glycans 782:811 Sialic acid-containing glycans 782:811 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 11 11 theme cow 1945:1947 arg1 glycans 1959:1965 both cow and sheep glycans 1940:1965 both cow and sheep glycans 1940:1965 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 6 12 theme protein 1375:1381 arg1 identification 1383:1396 protein identification 1375:1396 protein identification 1375:1396 Following glycan release and extraction, the protein could be digested within the gel with trypsin, and the masses of the tryptic peptides could be compared with those generated from a sequence database for protein identification. 9740055 3 13 theme in-gel 681:686 arg1 incubation 688:697 in-gel incubation 681:697 in-gel incubation with peptide N-glycosidase-F (PNGase-F) 681:737 N-linked glycans were then released by in-gel incubation with peptide N-glycosidase-F (PNGase-F) and extracted with water and acetonitrile. 9740055 9 14 used used 1676:1679 arg2 sheep 1657:1661 sheep 1657:1661 sheep 1657:1661 Thus, although all four species used N-acetyl-neuraminic acid, only cow and sheep additionally used N-glycolyl-neuraminic acid. 9740055 9 14 used used 1676:1679 arg2 cow 1649:1651 cow 1649:1651 cow 1649:1651 Thus, although all four species used N-acetyl-neuraminic acid, only cow and sheep additionally used N-glycolyl-neuraminic acid. 9740055 0 15 dep following 116:124 arg1 application 212:222 application 212:222 application to species-specific glycosylation of alpha1-acid glycoprotein 212:284 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 0 16 theme sulphate-polyacrylamide 166:188 arg1 gels 206:209 sodium dodecyl sulphate-polyacrylamide electrophoresis gels 151:209 sodium dodecyl sulphate-polyacrylamide electrophoresis gels 151:209 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 1 17 theme sulphate-polyacrylamide 480:502 arg1 electrophoresis 508:522 sodium dodecyl sulphate-polyacrylamide gel electrophoresis 465:522 sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) 465:533 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 1 17 theme sulphate-polyacrylamide 480:502 arg1 SDS-PAGE 525:532 SDS-PAGE 525:532 SDS-PAGE 525:532 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 11 18 gly Fucosylation 1880:1891 arg1 glycans 1911:1917 glycans 1911:1917 glycans from man and cow 1911:1934 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 19 link beta1-4-linked 2007:2020 arg1 beta1-3- 1986:1993 beta1-3- 1986:1993 beta1-3- 1986:1993 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 19 link beta1-4-linked 2007:2020 arg1 residues 2032:2039 beta1-4-linked galactose residues 2007:2039 beta1-4-linked galactose residues in the antennae 2007:2055 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 19 link beta1-4-linked 2007:2020 arg1 well 1999:2002 well 1999:2002 well 1999:2002 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 4 20 theme laser 1021:1025 arg1 spectrometry 1062:1073 matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry 1005:1073 matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry 1005:1073 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 6 21 theme sequence 1353:1360 arg1 database 1362:1369 a sequence database 1351:1369 a sequence database for protein identification 1351:1396 Following glycan release and extraction, the protein could be digested within the gel with trypsin, and the masses of the tryptic peptides could be compared with those generated from a sequence database for protein identification. 9740055 11 22 theme sheep 1953:1957 arg1 glycans 1959:1965 both cow and sheep glycans 1940:1965 both cow and sheep glycans 1940:1965 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 0 23 theme species-specific 227:242 arg1 glycosylation 244:256 species-specific glycosylation 227:256 species-specific glycosylation of alpha1-acid glycoprotein 227:284 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 6 24 theme glycan 1178:1183 arg1 release 1185:1191 glycan release 1178:1191 glycan release 1178:1191 Following glycan release and extraction, the protein could be digested within the gel with trypsin, and the masses of the tryptic peptides could be compared with those generated from a sequence database for protein identification. 9740055 0 25 theme desorption/ionization-mass 76:101 arg1 spectrometry 103:114 matrix-assisted laser desorption/ionization-mass spectrometry 54:114 matrix-assisted laser desorption/ionization-mass spectrometry 54:114 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 1 26 theme glycoproteins 433:445 arg1 separation 419:428 separation 419:428 separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) 419:533 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 0 27 gly glycosylation 244:256 arg1 glycoprotein 273:284 alpha1-acid glycoprotein 261:284 alpha1-acid glycoprotein 261:284 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 5 28 theme released 1108:1115 arg1 glycans 1117:1123 the released glycans 1104:1123 the released glycans 1104:1123 Structural determination of the released glycans was performed by exoglycosidase digestion. 9740055 9 29 used used 1613:1616 arg2 species 1605:1611 all four species 1596:1611 all four species 1596:1611 Thus, although all four species used N-acetyl-neuraminic acid, only cow and sheep additionally used N-glycolyl-neuraminic acid. 9740055 10 30 theme more 1803:1806 arg1 glycans 1821:1827 more triantennary glycans 1803:1827 more triantennary glycans 1803:1827 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 0 31 theme sodium 151:156 arg1 gels 206:209 sodium dodecyl sulphate-polyacrylamide electrophoresis gels 151:209 sodium dodecyl sulphate-polyacrylamide electrophoresis gels 151:209 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 1 32 theme sodium 465:470 arg1 electrophoresis 508:522 sodium dodecyl sulphate-polyacrylamide gel electrophoresis 465:522 sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) 465:533 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 1 32 theme sodium 465:470 arg1 SDS-PAGE 525:532 SDS-PAGE 525:532 SDS-PAGE 525:532 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 4 33 theme methyl 864:869 arg1 iodide 871:876 methyl iodide 864:876 methyl iodide 864:876 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 0 34 theme Structural 0:9 arg1 determination 11:23 Structural determination 0:23 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry 0:114 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 5 35 theme Structural 1076:1085 arg1 determination 1087:1099 Structural determination 1076:1099 Structural determination of the released glycans 1076:1123 Structural determination of the released glycans was performed by exoglycosidase digestion. 9740055 4 36 theme mixed-bed 932:940 arg1 column 942:947 a mixed-bed column 930:947 a mixed-bed column of ion-exchange resins 930:970 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 7 37 theme N-linked 1440:1447 arg1 glycans 1449:1455 N-linked glycans 1440:1455 N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog 1440:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 8 38 theme Major 1517:1521 arg1 differences 1540:1550 Major species-specific differences 1517:1550 Major species-specific differences in glycosylation 1517:1567 Major species-specific differences in glycosylation were found. 9740055 0 39 theme carbohydrates 37:49 arg1 determination 11:23 Structural determination 0:23 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry 0:114 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 10 40 theme tetraantennary 1857:1870 arg1 sugars 1872:1877 tetraantennary sugars 1857:1877 tetraantennary sugars 1857:1877 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 0 41 theme matrix-assisted 54:68 arg1 spectrometry 103:114 matrix-assisted laser desorption/ionization-mass spectrometry 54:114 matrix-assisted laser desorption/ionization-mass spectrometry 54:114 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 1 42 theme sensitive 310:318 arg1 method 320:325 a sensitive method 308:325 a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) 308:533 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 11 43 theme beta1-4-linked 2007:2020 arg1 beta1-3- 1986:1993 beta1-3- 1986:1993 beta1-3- 1986:1993 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 43 theme beta1-4-linked 2007:2020 arg1 residues 2032:2039 beta1-4-linked galactose residues 2007:2039 beta1-4-linked galactose residues in the antennae 2007:2055 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 43 theme beta1-4-linked 2007:2020 arg1 well 1999:2002 well 1999:2002 well 1999:2002 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 10 44 from carbohydrates 1750:1762 arg1 sheep 1772:1776 sheep 1772:1776 sheep 1772:1776 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 10 44 from carbohydrates 1750:1762 arg1 cow 1767:1769 cow 1767:1769 cow 1767:1769 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 10 44 from carbohydrates 1750:1762 arg1 dog 1782:1784 dog 1782:1784 dog 1782:1784 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 0 45 theme alpha1-acid 261:271 arg1 glycoprotein 273:284 alpha1-acid glycoprotein 261:284 alpha1-acid glycoprotein 261:284 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 0 46 link N-linked 28:35 arg1 carbohydrates 37:49 N-linked carbohydrates 28:49 N-linked carbohydrates 28:49 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 1 47 theme carbohydrates 352:364 arg1 analysis 331:338 analysis 331:338 analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) 331:533 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 7 48 link N-linked 1440:1447 arg1 glycans 1449:1455 N-linked glycans 1440:1455 N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog 1440:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 1 49 link N-linked 343:350 arg1 carbohydrates 352:364 N-linked carbohydrates 343:364 N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) 343:533 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 1 50 gly glycoproteins 433:445 arg1 glycoproteins 433:445 glycoproteins 433:445 glycoproteins (50-100 pmols) 433:460 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 1 50 gly glycoproteins 433:445 arg1 pmols 455:459 50-100 pmols 448:459 50-100 pmols 448:459 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 4 51 theme ion-exchange 952:963 arg1 resins 965:970 ion-exchange resins 952:970 ion-exchange resins 952:970 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 6 52 theme peptides 1298:1305 arg1 masses 1276:1281 the masses 1272:1281 the masses of the tryptic peptides 1272:1305 Following glycan release and extraction, the protein could be digested within the gel with trypsin, and the masses of the tryptic peptides could be compared with those generated from a sequence database for protein identification. 9740055 0 53 gly glycoprotein 273:284 arg1 glycoprotein 273:284 alpha1-acid glycoprotein 261:284 alpha1-acid glycoprotein 261:284 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 4 54 theme Sialic 782:787 arg1 glycans 805:811 Sialic acid-containing glycans 782:811 Sialic acid-containing glycans 782:811 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 0 55 theme electrophoresis 190:204 arg1 gels 206:209 sodium dodecyl sulphate-polyacrylamide electrophoresis gels 151:209 sodium dodecyl sulphate-polyacrylamide electrophoresis gels 151:209 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 4 56 theme MALDI 1050:1054 arg1 spectrometry 1062:1073 matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry 1005:1073 matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry 1005:1073 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 1 57 theme gel 504:506 arg1 electrophoresis 508:522 sodium dodecyl sulphate-polyacrylamide gel electrophoresis 465:522 sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) 465:533 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 1 57 theme gel 504:506 arg1 SDS-PAGE 525:532 SDS-PAGE 525:532 SDS-PAGE 525:532 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 3 58 theme peptide 704:710 arg1 PNGase-F 729:736 PNGase-F 729:736 PNGase-F 729:736 N-linked glycans were then released by in-gel incubation with peptide N-glycosidase-F (PNGase-F) and extracted with water and acetonitrile. 9740055 3 58 theme peptide 704:710 arg1 N-glycosidase-F 712:726 peptide N-glycosidase-F 704:726 peptide N-glycosidase-F (PNGase-F) 704:737 N-linked glycans were then released by in-gel incubation with peptide N-glycosidase-F (PNGase-F) and extracted with water and acetonitrile. 9740055 4 59 theme -mass 1056:1060 arg1 spectrometry 1062:1073 matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry 1005:1073 matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry 1005:1073 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 9 60 theme N-acetyl-neuraminic 1618:1636 arg1 acid 1638:1641 N-acetyl-neuraminic acid 1618:1641 N-acetyl-neuraminic acid 1618:1641 Thus, although all four species used N-acetyl-neuraminic acid, only cow and sheep additionally used N-glycolyl-neuraminic acid. 9740055 4 61 theme matrix-assisted 1005:1019 arg1 spectrometry 1062:1073 matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry 1005:1073 matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry 1005:1073 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 4 62 theme methyl 833:838 arg1 esters 840:845 methyl esters 833:845 methyl esters 833:845 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 4 63 theme desorption/ionization 1027:1047 arg1 spectrometry 1062:1073 matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry 1005:1073 matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry 1005:1073 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 11 64 from residues 2032:2039 arg1 antennae 2048:2055 the antennae 2044:2055 the antennae 2044:2055 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 10 65 theme predominant 1738:1748 arg1 glycans 1721:1727 Biantennary glycans 1709:1727 Biantennary glycans 1709:1727 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 10 65 theme predominant 1738:1748 arg1 carbohydrates 1750:1762 the predominant carbohydrates 1734:1762 the predominant carbohydrates in cow, sheep and dog 1734:1784 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 0 66 theme enzymatic 126:134 arg1 release 136:142 enzymatic release 126:142 enzymatic release 126:142 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 11 67 from man 1924:1926 arg1 glycans 1911:1917 glycans 1911:1917 glycans from man and cow 1911:1934 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 3 68 with incubation 688:697 arg1 PNGase-F 729:736 PNGase-F 729:736 PNGase-F 729:736 N-linked glycans were then released by in-gel incubation with peptide N-glycosidase-F (PNGase-F) and extracted with water and acetonitrile. 9740055 3 68 with incubation 688:697 arg1 N-glycosidase-F 712:726 peptide N-glycosidase-F 704:726 peptide N-glycosidase-F (PNGase-F) 704:737 N-linked glycans were then released by in-gel incubation with peptide N-glycosidase-F (PNGase-F) and extracted with water and acetonitrile. 9740055 3 69 link N-linked 642:649 arg1 glycans 651:657 N-linked glycans 642:657 N-linked glycans 642:657 N-linked glycans were then released by in-gel incubation with peptide N-glycosidase-F (PNGase-F) and extracted with water and acetonitrile. 9740055 9 70 theme N-glycolyl-neuraminic 1681:1701 arg1 acid 1703:1706 N-glycolyl-neuraminic acid 1681:1706 N-glycolyl-neuraminic acid 1681:1706 Thus, although all four species used N-acetyl-neuraminic acid, only cow and sheep additionally used N-glycolyl-neuraminic acid. 9740055 0 71 theme dodecyl 158:164 arg1 gels 206:209 sodium dodecyl sulphate-polyacrylamide electrophoresis gels 151:209 sodium dodecyl sulphate-polyacrylamide electrophoresis gels 151:209 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 7 72 gly glycoprotein 1474:1485 arg1 glycoprotein 1474:1485 alpha1-acid glycoprotein 1462:1485 alpha1-acid glycoprotein from man, cow, sheep and dog 1462:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 5 73 theme glycans 1117:1123 arg1 determination 1087:1099 Structural determination 1076:1099 Structural determination of the released glycans 1076:1123 Structural determination of the released glycans was performed by exoglycosidase digestion. 9740055 7 74 from man 1492:1494 arg1 glycoprotein 1474:1485 alpha1-acid glycoprotein 1462:1485 alpha1-acid glycoprotein from man, cow, sheep and dog 1462:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 7 75 theme alpha1-acid 1462:1472 arg1 glycoprotein 1474:1485 alpha1-acid glycoprotein 1462:1485 alpha1-acid glycoprotein from man, cow, sheep and dog 1462:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 1 76 theme dodecyl 472:478 arg1 electrophoresis 508:522 sodium dodecyl sulphate-polyacrylamide gel electrophoresis 465:522 sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) 465:533 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 1 76 theme dodecyl 472:478 arg1 SDS-PAGE 525:532 SDS-PAGE 525:532 SDS-PAGE 525:532 This paper describes a sensitive method for analysis of N-linked carbohydrates released enzymatically from within the gel following separation of glycoproteins (50-100 pmols) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 9740055 7 77 from cow 1497:1499 arg1 glycoprotein 1474:1485 alpha1-acid glycoprotein 1462:1485 alpha1-acid glycoprotein from man, cow, sheep and dog 1462:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 7 78 theme glycans 1449:1455 arg1 analysis 1428:1435 the analysis 1424:1435 the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog 1424:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 0 79 theme N-linked 28:35 arg1 carbohydrates 37:49 N-linked carbohydrates 28:49 N-linked carbohydrates 28:49 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 7 80 from sheep 1502:1506 arg1 glycoprotein 1474:1485 alpha1-acid glycoprotein 1462:1485 alpha1-acid glycoprotein from man, cow, sheep and dog 1462:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 2 81 theme separated 540:548 arg1 bands 550:554 The separated bands 536:554 The separated bands containing the glycoproteins 536:583 The separated bands containing the glycoproteins were cut from the gel, destained, reduced and alkylated. 9740055 7 82 from dog 1512:1514 arg1 glycoprotein 1474:1485 alpha1-acid glycoprotein 1462:1485 alpha1-acid glycoprotein from man, cow, sheep and dog 1462:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 10 83 theme triantennary 1808:1819 arg1 glycans 1821:1827 more triantennary glycans 1803:1827 more triantennary glycans 1803:1827 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 0 84 theme laser 70:74 arg1 spectrometry 103:114 matrix-assisted laser desorption/ionization-mass spectrometry 54:114 matrix-assisted laser desorption/ionization-mass spectrometry 54:114 Structural determination of N-linked carbohydrates by matrix-assisted laser desorption/ionization-mass spectrometry following enzymatic release within sodium dodecyl sulphate-polyacrylamide electrophoresis gels: application to species-specific glycosylation of alpha1-acid glycoprotein. 9740055 11 85 contain have 1981:1984 arg1 glycans 1959:1965 both cow and sheep glycans 1940:1965 both cow and sheep glycans 1940:1965 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 85 contain have 1981:1984 arg2 well 1999:2002 well 1999:2002 well 1999:2002 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 85 contain have 1981:1984 arg2 residues 2032:2039 beta1-4-linked galactose residues 2007:2039 beta1-4-linked galactose residues in the antennae 2007:2055 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 85 contain have 1981:1984 arg2 beta1-3- 1986:1993 beta1-3- 1986:1993 beta1-3- 1986:1993 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 2 86 gly glycoproteins 571:583 arg1 glycoproteins 571:583 the glycoproteins 567:583 the glycoproteins 567:583 The separated bands containing the glycoproteins were cut from the gel, destained, reduced and alkylated. 9740055 7 87 from analysis 1428:1435 arg1 glycoprotein 1474:1485 alpha1-acid glycoprotein 1462:1485 alpha1-acid glycoprotein from man, cow, sheep and dog 1462:1514 The method is applied to the analysis of N-linked glycans from alpha1-acid glycoprotein from man, cow, sheep and dog. 9740055 11 88 from cow 1932:1934 arg1 glycans 1911:1917 glycans 1911:1917 glycans from man and cow 1911:1934 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 8 89 theme species-specific 1523:1538 arg1 differences 1540:1550 Major species-specific differences 1517:1550 Major species-specific differences in glycosylation 1517:1567 Major species-specific differences in glycosylation were found. 9740055 10 90 theme substantial 1835:1845 arg1 amount 1847:1852 a substantial amount 1833:1852 a substantial amount of tetraantennary sugars 1833:1877 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 10 90 theme substantial 1835:1845 arg1 sugars 1872:1877 tetraantennary sugars 1857:1877 tetraantennary sugars 1857:1877 Biantennary glycans were the predominant carbohydrates in cow, sheep and dog but man produced more triantennary glycans and a substantial amount of tetraantennary sugars. 9740055 5 91 theme exoglycosidase 1142:1155 arg1 digestion 1157:1165 exoglycosidase digestion 1142:1165 exoglycosidase digestion 1142:1165 Structural determination of the released glycans was performed by exoglycosidase digestion. 9740055 4 92 with reaction 850:857 arg1 iodide 871:876 methyl iodide 864:876 methyl iodide 864:876 Sialic acid-containing glycans were converted into methyl esters by reaction with methyl iodide, salts and reagents were removed by passage through a mixed-bed column of ion-exchange resins and the glycans were examined by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. 9740055 11 93 located found 1902:1906 arg1 glycans 1911:1917 glycans 1911:1917 glycans from man and cow 1911:1934 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 93 located found 1902:1906 arg2 Fucosylation 1880:1891 Fucosylation 1880:1891 Fucosylation 1880:1891 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 94 theme galactose 2022:2030 arg1 beta1-3- 1986:1993 beta1-3- 1986:1993 beta1-3- 1986:1993 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 94 theme galactose 2022:2030 arg1 residues 2032:2039 beta1-4-linked galactose residues 2007:2039 beta1-4-linked galactose residues in the antennae 2007:2055 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 9740055 11 94 theme galactose 2022:2030 arg1 well 1999:2002 well 1999:2002 well 1999:2002 Fucosylation was only found in glycans from man and cow and both cow and sheep glycans were found to have beta1-3- and well as beta1-4-linked galactose residues in the antennae. 7117239 3 0 theme following 523:531 arg1 structure 533:541 the following structure 519:541 the following structure 519:541 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 0 1 theme A 91:91 arg1 sialoglycans 49:60 sialoglycans 49:60 sialoglycans of secretory immunoglobulins A from human milk 49:107 Primary structure of the N-glycosidically linked sialoglycans of secretory immunoglobulins A from human milk. 7117239 4 2 theme alpha 777:781 arg1 1-6 783:785 alpha 1-6 777:785 alpha 1-6 777:785 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 4 2 theme alpha 777:781 arg1 Gal 738:740 Gal 738:740 Gal(beta 1-3) (glycopeptide D) 738:767 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 1 3 theme human 183:187 arg1 milk 189:192 human milk 183:192 human milk 183:192 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 3 4 dep see 569:571 arg1 formula 560:566 formula 560:566 formula 560:566 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 4 5 theme glycopeptide 789:800 arg1 E 802:802 glycopeptide E 789:802 glycopeptide E 789:802 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 4 5 theme glycopeptide 789:800 arg1 Gal 738:740 Gal 738:740 Gal(beta 1-3) (glycopeptide D) 738:767 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 0 6 theme human 98:102 arg1 milk 104:107 human milk 98:107 human milk 98:107 Primary structure of the N-glycosidically linked sialoglycans of secretory immunoglobulins A from human milk. 7117239 5 7 theme alpha 858:862 arg1 linkage 869:875 (alpha 1-3) linkage 857:875 (alpha 1-3) linkage 857:875 Furthermore, in glycopeptide C a fucose residue in (alpha 1-3) linkage to GlcNAc-5' could be traced. 7117239 2 8 theme them 360:363 arg1 them 360:363 them 360:363 them 360:363 The structures of five of them have been determined on the basis of the results obtained by methylation analysis, mass spectrometry and 360 MHz 1H-NMR spectroscopy. 7117239 2 8 theme them 360:363 arg1 five 352:355 five 352:355 five 352:355 The structures of five of them have been determined on the basis of the results obtained by methylation analysis, mass spectrometry and 360 MHz 1H-NMR spectroscopy. 7117239 0 9 from sialoglycans 49:60 arg1 milk 104:107 human milk 98:107 human milk 98:107 Primary structure of the N-glycosidically linked sialoglycans of secretory immunoglobulins A from human milk. 7117239 3 10 dep glycopeptides 589:601 arg1 see 569:571 see 569:571 see text 569:576 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 4 11 theme following 658:666 arg1 extensions 668:677 The following extensions 654:677 The following extensions to Gal-6' 654:687 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 4 12 gly glycopeptide 721:732 arg2 glycopeptide 721:732 glycopeptide A 721:734 glycopeptide A 721:734 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 2 13 theme 360 470:472 arg1 spectroscopy 485:496 360 MHz 1H-NMR spectroscopy 470:496 360 MHz 1H-NMR spectroscopy 470:496 The structures of five of them have been determined on the basis of the results obtained by methylation analysis, mass spectrometry and 360 MHz 1H-NMR spectroscopy. 7117239 4 14 gly glycopeptide 753:764 arg2 glycopeptide 753:764 glycopeptide D 753:766 glycopeptide D 753:766 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 2 15 theme MHz 474:476 arg1 spectroscopy 485:496 360 MHz 1H-NMR spectroscopy 470:496 360 MHz 1H-NMR spectroscopy 470:496 The structures of five of them have been determined on the basis of the results obtained by methylation analysis, mass spectrometry and 360 MHz 1H-NMR spectroscopy. 7117239 1 16 gly glycopeptides 237:249 arg2 glycopeptides 237:249 the alkali-labile glycopeptides 219:249 the alkali-labile glycopeptides 219:249 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 2 17 theme results 406:412 arg1 basis 393:397 the basis 389:397 the basis of the results obtained by methylation analysis, mass spectrometry and 360 MHz 1H-NMR spectroscopy 389:496 The structures of five of them have been determined on the basis of the results obtained by methylation analysis, mass spectrometry and 360 MHz 1H-NMR spectroscopy. 7117239 0 18 theme Primary 0:6 arg1 structure 8:16 Primary structure 0:16 Primary structure of the N-glycosidically 0:40 Primary structure of the N-glycosidically linked sialoglycans of secretory immunoglobulins A from human milk. 7117239 1 19 theme ion-exchange 305:316 arg1 chromatography 318:331 ion-exchange chromatography 305:331 ion-exchange chromatography 305:331 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 2 20 theme five 352:355 arg1 structures 338:347 The structures 334:347 The structures of five of them 334:363 The structures of five of them have been determined on the basis of the results obtained by methylation analysis, mass spectrometry and 360 MHz 1H-NMR spectroscopy. 7117239 4 21 gly glycopeptide 789:800 arg2 glycopeptide 789:800 glycopeptide E 789:802 glycopeptide E 789:802 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 1 22 gly sialoglycopeptides 128:145 arg1 A 176:176 secretory immunoglobulins A 150:176 secretory immunoglobulins A from human milk 150:192 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 1 22 gly sialoglycopeptides 128:145 arg2 sialoglycopeptides 128:145 The alkali-stable sialoglycopeptides 110:145 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk 110:192 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 1 23 from sialoglycopeptides 128:145 arg1 milk 189:192 human milk 183:192 human milk 183:192 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 4 24 theme glycopeptide 721:732 arg1 NeuAc 703:707 NeuAc 703:707 NeuAc(alpha 2-6) (glycopeptide A) 703:735 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 4 24 theme glycopeptide 721:732 arg1 A 734:734 glycopeptide A 721:734 glycopeptide A 721:734 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 2 25 theme mass 448:451 arg1 spectrometry 453:464 mass spectrometry 448:464 mass spectrometry 448:464 The structures of five of them have been determined on the basis of the results obtained by methylation analysis, mass spectrometry and 360 MHz 1H-NMR spectroscopy. 7117239 5 26 theme fucose 839:844 arg1 residue 846:852 a fucose residue 837:852 a fucose residue in (alpha 1-3) linkage to GlcNAc-5' 837:888 Furthermore, in glycopeptide C a fucose residue in (alpha 1-3) linkage to GlcNAc-5' could be traced. 7117239 3 27 theme structure 643:651 arg1 glycopeptides 589:601 The other glycopeptides 579:601 (formula; see text) The other glycopeptides 559:601 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 3 27 theme structure 643:651 arg1 extensions 624:633 extensions 624:633 extensions of this structure 624:651 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 3 28 gly glycopeptide 503:514 arg2 glycopeptide 503:514 glycopeptide B 503:516 glycopeptide B 503:516 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 3 29 gly glycopeptides 589:601 arg2 extensions 624:633 extensions 624:633 extensions of this structure 624:651 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 3 29 gly glycopeptides 589:601 arg2 glycopeptides 589:601 The other glycopeptides 579:601 (formula; see text) The other glycopeptides 559:601 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 4 30 theme glycopeptide 753:764 arg1 D 766:766 glycopeptide D 753:766 glycopeptide D 753:766 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 4 30 theme glycopeptide 753:764 arg1 Gal 738:740 Gal 738:740 Gal(beta 1-3) (glycopeptide D) 738:767 The following extensions to Gal-6' are proposed: NeuAc(alpha 2-6) (glycopeptide A), Gal(beta 1-3) (glycopeptide D) and Fuc(alpha 1-6) (glycopeptide E). 7117239 1 31 theme alkali-labile 223:235 arg1 glycopeptides 237:249 the alkali-labile glycopeptides 219:249 the alkali-labile glycopeptides 219:249 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 0 32 theme N-glycosidically 25:40 arg1 structure 8:16 Primary structure 0:16 Primary structure of the N-glycosidically 0:40 Primary structure of the N-glycosidically linked sialoglycans of secretory immunoglobulins A from human milk. 7117239 5 33 gly glycopeptide 822:833 arg2 glycopeptide 822:833 glycopeptide C 822:835 glycopeptide C 822:835 Furthermore, in glycopeptide C a fucose residue in (alpha 1-3) linkage to GlcNAc-5' could be traced. 7117239 2 34 theme methylation 426:436 arg1 analysis 438:445 methylation analysis 426:445 methylation analysis 426:445 The structures of five of them have been determined on the basis of the results obtained by methylation analysis, mass spectrometry and 360 MHz 1H-NMR spectroscopy. 7117239 1 35 theme alkali-stable 114:126 arg1 sialoglycopeptides 128:145 The alkali-stable sialoglycopeptides 110:145 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk 110:192 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 2 36 theme 1H-NMR 478:483 arg1 spectroscopy 485:496 360 MHz 1H-NMR spectroscopy 470:496 360 MHz 1H-NMR spectroscopy 470:496 The structures of five of them have been determined on the basis of the results obtained by methylation analysis, mass spectrometry and 360 MHz 1H-NMR spectroscopy. 7117239 3 37 theme other 583:587 arg1 glycopeptides 589:601 The other glycopeptides 579:601 (formula; see text) The other glycopeptides 559:601 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 3 37 theme other 583:587 arg1 extensions 624:633 extensions 624:633 extensions of this structure 624:651 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 5 38 theme glycopeptide 822:833 arg1 C 835:835 glycopeptide C 822:835 glycopeptide C 822:835 Furthermore, in glycopeptide C a fucose residue in (alpha 1-3) linkage to GlcNAc-5' could be traced. 7117239 5 39 from residue 846:852 arg1 linkage 869:875 (alpha 1-3) linkage 857:875 (alpha 1-3) linkage 857:875 Furthermore, in glycopeptide C a fucose residue in (alpha 1-3) linkage to GlcNAc-5' could be traced. 7117239 1 40 gly asialoglycopeptides 282:300 arg2 asialoglycopeptides 282:300 the asialoglycopeptides 278:300 the asialoglycopeptides 278:300 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 3 41 theme glycopeptide 503:514 arg1 B 516:516 glycopeptide B 503:516 glycopeptide B 503:516 For glycopeptide B, the following structure has been found: (formula; see text) The other glycopeptides can be considered as extensions of this structure. 7117239 0 42 from milk 104:107 arg1 A 91:91 secretory immunoglobulins A 65:91 secretory immunoglobulins A from human milk 65:107 Primary structure of the N-glycosidically linked sialoglycans of secretory immunoglobulins A from human milk. 7117239 0 42 from milk 104:107 arg1 sialoglycans 49:60 sialoglycans 49:60 sialoglycans of secretory immunoglobulins A from human milk 49:107 Primary structure of the N-glycosidically linked sialoglycans of secretory immunoglobulins A from human milk. 7117239 1 43 theme secretory 150:158 arg1 A 176:176 secretory immunoglobulins A 150:176 secretory immunoglobulins A from human milk 150:192 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 1 44 theme gel 254:256 arg1 filtration 258:267 gel filtration 254:267 gel filtration 254:267 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 0 45 theme immunoglobulins 75:89 arg1 A 91:91 secretory immunoglobulins A 65:91 secretory immunoglobulins A from human milk 65:107 Primary structure of the N-glycosidically linked sialoglycans of secretory immunoglobulins A from human milk. 7117239 1 46 theme immunoglobulins 160:174 arg1 A 176:176 secretory immunoglobulins A 150:176 secretory immunoglobulins A from human milk 150:192 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 0 47 theme secretory 65:73 arg1 A 91:91 secretory immunoglobulins A 65:91 secretory immunoglobulins A from human milk 65:107 Primary structure of the N-glycosidically linked sialoglycans of secretory immunoglobulins A from human milk. 7117239 1 48 from milk 189:192 arg1 A 176:176 secretory immunoglobulins A 150:176 secretory immunoglobulins A from human milk 150:192 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 1 48 from milk 189:192 arg1 sialoglycopeptides 128:145 The alkali-stable sialoglycopeptides 110:145 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk 110:192 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 7117239 1 49 theme A 176:176 arg1 sialoglycopeptides 128:145 The alkali-stable sialoglycopeptides 110:145 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk 110:192 The alkali-stable sialoglycopeptides of secretory immunoglobulins A from human milk have been separated from the alkali-labile glycopeptides by gel filtration and from the asialoglycopeptides by ion-exchange chromatography. 24698316 6 0 theme mutational 1018:1027 arg1 analysis 1029:1036 mutational analysis 1018:1036 mutational analysis 1018:1036 METHODS After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. 24698316 6 1 from Tunisia 1009:1015 arg1 HIES 999:1002 HIES 999:1002 HIES from Tunisia 999:1015 METHODS After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. 24698316 2 2 theme genetic 268:274 arg1 causes 276:281 Known genetic causes 262:281 Known genetic causes for HIES 262:290 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 2 theme genetic 268:274 arg1 mutations 296:304 mutations 296:304 mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways 296:457 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 15 3 theme development 2173:2183 arg1 error 2164:2168 a novel primary (inborn) error 2139:2168 a novel primary (inborn) error of development and immunity 2139:2196 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 14 4 contain had 2028:2030 arg1 patients 2019:2026 Most patients 2014:2026 Most patients 2014:2026 Most patients had developmental delay, and many had psychomotor retardation. 24698316 14 4 contain had 2028:2030 arg2 delay 2046:2050 developmental delay 2032:2050 developmental delay 2032:2050 Most patients had developmental delay, and many had psychomotor retardation. 24698316 0 5 theme Hypomorphic 0:10 arg1 mutations 23:31 Hypomorphic homozygous mutations 0:31 Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) 0:62 Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. 24698316 15 6 theme biallelic 2206:2214 arg1 mutations 2228:2236 biallelic hypomorphic mutations 2206:2236 biallelic hypomorphic mutations 2206:2236 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 1 7 theme increased 177:185 arg1 levels 197:202 increased serum IgE levels 177:202 increased serum IgE levels 177:202 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 24698316 10 8 theme third 1540:1544 arg1 mutation 1557:1564 A third homozygous mutation 1538:1564 A third homozygous mutation (p.Asp502Tyr) 1538:1578 A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. 24698316 10 8 theme third 1540:1544 arg1 p.Asp502Tyr 1567:1577 p.Asp502Tyr 1567:1577 p.Asp502Tyr 1567:1577 A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. 24698316 11 9 theme diphosphate 1758:1768 arg1 N-acetylglucosamine 1770:1788 uridine diphosphate N-acetylglucosamine 1750:1788 uridine diphosphate N-acetylglucosamine 1750:1788 These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. 24698316 1 10 theme IgE 193:195 arg1 levels 197:202 increased serum IgE levels 177:202 increased serum IgE levels 177:202 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 24698316 8 11 theme Mutational 1230:1239 arg1 analysis 1241:1248 Mutational analysis 1230:1248 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families 1222:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 5 12 theme genetic 796:802 arg1 cause 804:808 the genetic cause 792:808 the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8 792:875 OBJECTIVE We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. 24698316 8 13 theme disease 1408:1414 arg1 status 1416:1421 disease status 1408:1421 disease status 1408:1421 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 1 14 theme BACKGROUND 111:120 arg1 infections 153:162 BACKGROUND Recurrent bacterial and fungal infections 111:162 BACKGROUND Recurrent bacterial and fungal infections 111:162 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 24698316 5 15 contain carry 843:847 arg2 mutations 849:857 mutations 849:857 mutations in STAT3 or DOCK8 849:875 OBJECTIVE We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. 24698316 5 15 contain carry 843:847 arg1 patients 813:820 patients 813:820 patients with HIES who do not carry mutations in STAT3 or DOCK8 813:875 OBJECTIVE We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. 24698316 9 16 dep PGM3 1503:1506 arg1 p.Glu340del 1509:1519 p.Glu340del 1509:1519 p.Glu340del 1509:1519 The mutations predict amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser). 24698316 9 16 dep PGM3 1503:1506 arg1 p.Leu83Ser 1525:1534 p.Leu83Ser 1525:1534 p.Leu83Ser 1525:1534 The mutations predict amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser). 24698316 1 17 theme bacterial 132:140 arg1 infections 153:162 BACKGROUND Recurrent bacterial and fungal infections 111:162 BACKGROUND Recurrent bacterial and fungal infections 111:162 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 24698316 11 18 contain have 1695:1698 arg1 mutations 1685:1693 These hypomorphic mutations 1667:1693 These hypomorphic mutations 1667:1693 These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. 24698316 11 18 contain have 1695:1698 arg2 effect 1703:1708 an effect 1700:1708 an effect 1700:1708 These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. 24698316 8 19 theme genes 1263:1267 arg1 analysis 1241:1248 Mutational analysis 1230:1248 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families 1222:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 8 20 theme recessive 1436:1444 arg1 inheritance 1446:1456 recessive inheritance 1436:1456 recessive inheritance 1436:1456 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 13 21 theme T-cell 1946:1951 arg1 proliferation 1953:1965 T-cell proliferation 1946:1965 T-cell proliferation 1946:1965 T-cell proliferation and differentiation were impaired in patients. 24698316 5 22 from cause 804:808 arg1 patients 813:820 patients 813:820 patients with HIES who do not carry mutations in STAT3 or DOCK8 813:875 OBJECTIVE We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. 24698316 9 23 theme acid 1487:1490 arg1 changes 1492:1498 amino acid changes 1481:1498 amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser) 1481:1535 The mutations predict amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser). 24698316 6 24 theme SNPchip 936:942 arg1 genotyping 944:953 SNPchip genotyping 936:953 SNPchip genotyping 936:953 METHODS After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. 24698316 2 25 theme transduction 437:448 arg1 pathways 450:457 signal transduction pathways 430:457 signal transduction pathways 430:457 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 0 26 from mutations 23:31 arg1 phosphoglucomutase 36:53 phosphoglucomutase 3 36:55 phosphoglucomutase 3 (PGM3) 36:62 Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. 24698316 0 26 from mutations 23:31 arg1 PGM3 58:61 PGM3 58:61 PGM3 58:61 Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. 24698316 8 27 theme linkage 1283:1289 arg1 region 1291:1296 an 11.9-Mb linkage region 1272:1296 an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families 1272:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 12 28 theme tetra-antennary 1919:1933 arg1 N-glycans 1935:1943 tri-antennary and tetra-antennary N-glycans 1901:1943 tri-antennary and tetra-antennary N-glycans 1901:1943 Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. 24698316 8 29 from genes 1263:1267 arg1 chromosome 1301:1310 chromosome 6 1301:1312 chromosome 6 1301:1312 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 8 29 from genes 1263:1267 arg1 region 1291:1296 an 11.9-Mb linkage region 1272:1296 an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families 1272:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 2 30 from mutations 296:304 arg1 transducer 316:325 signal transducer 309:325 signal transducer 309:325 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 30 from mutations 296:304 arg1 DOCK8 400:404 DOCK8 400:404 DOCK8 400:404 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 30 from mutations 296:304 arg1 activator 331:339 activator 331:339 activator 331:339 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 30 from mutations 296:304 arg1 dedicator 372:380 dedicator 372:380 dedicator of cytokinesis 8 372:397 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 30 from mutations 296:304 arg1 STAT3 361:365 STAT3 361:365 STAT3 361:365 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 11 31 theme biosynthetic 1717:1728 arg1 reactions 1730:1738 the biosynthetic reactions 1713:1738 the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine 1713:1788 These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. 24698316 8 32 dep RESULTS 1222:1228 arg1 analysis 1241:1248 Mutational analysis 1230:1248 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families 1222:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 15 33 theme impaired 2258:2265 arg1 glycosylation 2267:2279 impaired glycosylation 2258:2279 impaired glycosylation 2258:2279 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 10 34 theme other 1628:1632 arg1 families 1643:1650 2 other affected families 1626:1650 2 other affected families 1626:1650 A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. 24698316 0 35 theme IgE 99:101 arg1 levels 103:108 serum IgE levels 93:108 serum IgE levels 93:108 Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. 24698316 4 36 theme diphosphate 673:683 arg1 N-acetylglucosamine 685:703 uridine diphosphate N-acetylglucosamine 665:703 uridine diphosphate N-acetylglucosamine 665:703 One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. 24698316 3 37 with patients 518:525 arg1 HIES 532:535 HIES 532:535 HIES 532:535 However, glycosylation defects have not been described in patients with HIES. 24698316 12 38 theme tri-antennary 1901:1913 arg1 N-glycans 1935:1943 tri-antennary and tetra-antennary N-glycans 1901:1943 tri-antennary and tetra-antennary N-glycans 1901:1943 Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. 24698316 8 39 theme multiplex 1326:1334 arg1 families 1336:1343 2 multiplex families 1324:1343 2 multiplex families 1324:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 10 40 theme affected 1634:1641 arg1 families 1643:1650 2 other affected families 1626:1650 2 other affected families 1626:1650 A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. 24698316 14 41 theme Most 2014:2017 arg1 patients 2019:2026 Most patients 2014:2026 Most patients 2014:2026 Most patients had developmental delay, and many had psychomotor retardation. 24698316 7 42 theme Protein 1101:1107 arg1 expression 1109:1118 Protein expression 1101:1118 Protein expression 1101:1118 Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. 24698316 15 43 theme inborn 2156:2161 arg1 error 2164:2168 a novel primary (inborn) error 2139:2168 a novel primary (inborn) error of development and immunity 2139:2196 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 5 44 with patients 813:820 arg1 HIES 827:830 HIES 827:830 HIES 827:830 OBJECTIVE We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. 24698316 8 45 theme homozygous 1358:1367 arg1 mutations 1369:1377 2 homozygous mutations 1356:1377 2 homozygous mutations in PGM3 that segregated with disease status 1356:1421 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 12 46 theme glycosylation 1830:1842 arg1 pattern 1844:1850 an aberrant glycosylation pattern 1818:1850 an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans 1818:1943 Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. 24698316 15 47 theme primary 2147:2153 arg1 error 2164:2168 a novel primary (inborn) error 2139:2168 a novel primary (inborn) error of development and immunity 2139:2196 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 12 48 theme aberrant 1821:1828 arg1 pattern 1844:1850 an aberrant glycosylation pattern 1818:1850 an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans 1818:1943 Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. 24698316 6 49 theme selector-based 1057:1070 arg1 sequencing 1089:1098 selector-based, high-throughput sequencing 1057:1098 selector-based, high-throughput sequencing 1057:1098 METHODS After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. 24698316 14 50 theme psychomotor 2066:2076 arg1 retardation 2078:2088 psychomotor retardation 2066:2088 psychomotor retardation 2066:2088 Most patients had developmental delay, and many had psychomotor retardation. 24698316 2 51 theme signal 309:314 arg1 transducer 316:325 signal transducer 309:325 signal transducer 309:325 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 51 theme signal 309:314 arg1 STAT3 361:365 STAT3 361:365 STAT3 361:365 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 51 theme signal 309:314 arg1 DOCK8 400:404 DOCK8 400:404 DOCK8 400:404 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 8 52 from chromosome 1301:1310 arg1 genes 1263:1267 candidate genes 1253:1267 candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families 1253:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 6 53 with families 985:992 arg1 HIES 999:1002 HIES 999:1002 HIES from Tunisia 999:1015 METHODS After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. 24698316 1 54 theme fungal 146:151 arg1 infections 153:162 BACKGROUND Recurrent bacterial and fungal infections 111:162 BACKGROUND Recurrent bacterial and fungal infections 111:162 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 24698316 11 55 theme hypomorphic 1673:1683 arg1 mutations 1685:1693 These hypomorphic mutations 1667:1693 These hypomorphic mutations 1667:1693 These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. 24698316 4 56 theme N-glycans 748:756 arg1 biosynthesis 732:743 the biosynthesis 728:743 the biosynthesis of N-glycans 728:756 One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. 24698316 3 57 theme glycosylation 469:481 arg1 defects 483:489 glycosylation defects 469:489 glycosylation defects 469:489 However, glycosylation defects have not been described in patients with HIES. 24698316 8 58 from region 1291:1296 arg1 chromosome 1301:1310 chromosome 6 1301:1312 chromosome 6 1301:1312 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 8 58 from region 1291:1296 arg1 analysis 1241:1248 Mutational analysis 1230:1248 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families 1222:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 1 59 with patients 217:224 arg1 HIES 255:258 HIES 255:258 HIES 255:258 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 24698316 1 59 with patients 217:224 arg1 syndrome 245:252 the hyper-IgE syndrome 231:252 the hyper-IgE syndrome (HIES) 231:259 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 24698316 7 60 theme mass 1203:1206 arg1 spectrometry 1208:1219 mass spectrometry 1203:1219 mass spectrometry 1203:1219 Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. 24698316 4 61 theme glycosylation 564:576 arg1 pathway 578:584 the glycosylation pathway 560:584 the glycosylation pathway 560:584 One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. 24698316 9 62 from changes 1492:1498 arg1 PGM3 1503:1506 PGM3 1503:1506 PGM3 (p.Glu340del and p.Leu83Ser) 1503:1535 The mutations predict amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser). 24698316 5 63 dep OBJECTIVE 759:767 arg1 sought 772:777 sought 772:777 sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8 772:875 OBJECTIVE We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. 24698316 4 64 theme crucial 542:548 arg1 enzyme 550:555 One crucial enzyme 538:555 One crucial enzyme in the glycosylation pathway 538:584 One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. 24698316 2 65 theme Known 262:266 arg1 causes 276:281 Known genetic causes 262:281 Known genetic causes for HIES 262:290 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 65 theme Known 262:266 arg1 mutations 296:304 mutations 296:304 mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways 296:457 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 15 66 theme immunity 2189:2196 arg1 error 2164:2168 a novel primary (inborn) error 2139:2168 a novel primary (inborn) error of development and immunity 2139:2196 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 6 67 theme linkage 907:913 arg1 interval 915:922 a linkage interval 905:922 a linkage interval 905:922 METHODS After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. 24698316 10 68 theme homozygous 1546:1555 arg1 mutation 1557:1564 A third homozygous mutation 1538:1564 A third homozygous mutation (p.Asp502Tyr) 1538:1578 A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. 24698316 10 68 theme homozygous 1546:1555 arg1 p.Asp502Tyr 1567:1577 p.Asp502Tyr 1567:1577 p.Asp502Tyr 1567:1577 A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. 24698316 1 69 theme serum 187:191 arg1 levels 197:202 increased serum IgE levels 177:202 increased serum IgE levels 177:202 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 24698316 8 70 theme 11.9-Mb 1275:1281 arg1 region 1291:1296 an 11.9-Mb linkage region 1272:1296 an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families 1272:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 8 71 from mutations 1369:1377 arg1 PGM3 1382:1385 PGM3 1382:1385 PGM3 1382:1385 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 6 72 dep METHODS 878:884 arg1 performed 1042:1050 performed 1042:1050 was performed with selector-based, high-throughput sequencing 1038:1098 METHODS After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. 24698316 7 73 theme Western 1145:1151 arg1 blotting 1153:1160 Western blotting 1145:1160 Western blotting 1145:1160 Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. 24698316 12 74 from pattern 1844:1850 arg1 leukocytes 1855:1864 leukocytes 1855:1864 leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans 1855:1943 Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. 24698316 1 75 theme Recurrent 122:130 arg1 infections 153:162 BACKGROUND Recurrent bacterial and fungal infections 111:162 BACKGROUND Recurrent bacterial and fungal infections 111:162 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 24698316 6 76 theme homozygosity 959:970 arg1 mapping 972:978 homozygosity mapping 959:978 homozygosity mapping 959:978 METHODS After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. 24698316 14 77 contain had 2062:2064 arg2 retardation 2078:2088 psychomotor retardation 2066:2088 psychomotor retardation 2066:2088 Most patients had developmental delay, and many had psychomotor retardation. 24698316 14 77 contain had 2062:2064 arg1 many 2057:2060 many 2057:2060 many 2057:2060 Most patients had developmental delay, and many had psychomotor retardation. 24698316 8 78 theme candidate 1253:1261 arg1 genes 1263:1267 candidate genes 1253:1267 candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families 1253:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 9 79 theme amino 1481:1485 arg1 changes 1492:1498 amino acid changes 1481:1498 amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser) 1481:1535 The mutations predict amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser). 24698316 12 80 theme N-glycans 1935:1943 arg1 level 1892:1896 a reduced level 1882:1896 a reduced level of tri-antennary and tetra-antennary N-glycans 1882:1943 Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. 24698316 15 81 theme hypomorphic 2216:2226 arg1 mutations 2228:2236 biallelic hypomorphic mutations 2206:2236 biallelic hypomorphic mutations 2206:2236 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 2 82 theme signal 430:435 arg1 pathways 450:457 signal transduction pathways 430:457 signal transduction pathways 430:457 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 4 83 theme key 636:638 arg1 step 640:643 a key step 634:643 a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans 634:756 One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. 24698316 11 84 theme uridine 1750:1756 arg1 N-acetylglucosamine 1770:1788 uridine diphosphate N-acetylglucosamine 1750:1788 uridine diphosphate N-acetylglucosamine 1750:1788 These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. 24698316 0 85 theme serum 93:97 arg1 levels 103:108 serum IgE levels 93:108 serum IgE levels 93:108 Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. 24698316 15 86 theme PGM3 2116:2119 arg1 function 2121:2128 PGM3 function 2116:2128 PGM3 function 2116:2128 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 8 87 from analysis 1241:1248 arg1 region 1291:1296 an 11.9-Mb linkage region 1272:1296 an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families 1272:1343 RESULTS Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. 24698316 15 88 theme CONCLUSION 2091:2100 arg1 Impairment 2102:2111 CONCLUSION Impairment 2091:2111 CONCLUSION Impairment of PGM3 function 2091:2128 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 0 89 theme homozygous 12:21 arg1 mutations 23:31 Hypomorphic homozygous mutations 0:31 Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) 0:62 Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. 24698316 14 90 theme developmental 2032:2044 arg1 delay 2046:2050 developmental delay 2032:2050 developmental delay 2032:2050 Most patients had developmental delay, and many had psychomotor retardation. 24698316 4 91 theme uridine 665:671 arg1 N-acetylglucosamine 685:703 uridine diphosphate N-acetylglucosamine 665:703 uridine diphosphate N-acetylglucosamine 665:703 One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. 24698316 4 92 from enzyme 550:555 arg1 pathway 578:584 the glycosylation pathway 560:584 the glycosylation pathway 560:584 One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. 24698316 10 93 theme p.Leu83Ser 1588:1597 arg1 variant 1599:1605 the p.Leu83Ser variant 1584:1605 the p.Leu83Ser variant 1584:1605 A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. 24698316 5 94 from mutations 849:857 arg1 DOCK8 871:875 DOCK8 871:875 DOCK8 871:875 OBJECTIVE We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. 24698316 5 94 from mutations 849:857 arg1 STAT3 862:866 STAT3 862:866 STAT3 862:866 OBJECTIVE We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. 24698316 4 95 theme N-acetylglucosamine 685:703 arg1 synthesis 652:660 the synthesis 648:660 the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans 648:756 One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. 24698316 2 96 theme cytokinesis 385:395 arg1 transducer 316:325 signal transducer 309:325 signal transducer 309:325 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 96 theme cytokinesis 385:395 arg1 DOCK8 400:404 DOCK8 400:404 DOCK8 400:404 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 96 theme cytokinesis 385:395 arg1 dedicator 372:380 dedicator 372:380 dedicator of cytokinesis 8 372:397 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 96 theme cytokinesis 385:395 arg1 activator 331:339 activator 331:339 activator 331:339 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 96 theme cytokinesis 385:395 arg1 STAT3 361:365 STAT3 361:365 STAT3 361:365 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 12 97 theme reduced 1884:1890 arg1 level 1892:1896 a reduced level 1882:1896 a reduced level of tri-antennary and tetra-antennary N-glycans 1882:1943 Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. 24698316 15 98 theme novel 2141:2145 arg1 error 2164:2168 a novel primary (inborn) error 2139:2168 a novel primary (inborn) error of development and immunity 2139:2196 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 15 99 theme hyper-IgE-like 2287:2300 arg1 phenotype 2302:2310 a hyper-IgE-like phenotype 2285:2310 a hyper-IgE-like phenotype 2285:2310 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 12 100 theme Glycomic 1791:1798 arg1 analysis 1800:1807 Glycomic analysis 1791:1807 Glycomic analysis 1791:1807 Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. 24698316 15 101 theme function 2121:2128 arg1 Impairment 2102:2111 CONCLUSION Impairment 2091:2111 CONCLUSION Impairment of PGM3 function 2091:2128 CONCLUSION Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. 24698316 6 102 dep selector-based 1057:1070 arg1 high-throughput 1073:1087 high-throughput 1073:1087 high-throughput 1073:1087 METHODS After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. 24698316 2 103 theme transcription 344:356 arg1 transducer 316:325 signal transducer 309:325 signal transducer 309:325 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 103 theme transcription 344:356 arg1 DOCK8 400:404 DOCK8 400:404 DOCK8 400:404 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 103 theme transcription 344:356 arg1 dedicator 372:380 dedicator 372:380 dedicator of cytokinesis 8 372:397 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 103 theme transcription 344:356 arg1 activator 331:339 activator 331:339 activator 331:339 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 2 103 theme transcription 344:356 arg1 STAT3 361:365 STAT3 361:365 STAT3 361:365 Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. 24698316 4 104 from step 640:643 arg1 synthesis 652:660 the synthesis 648:660 the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans 648:756 One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. 24698316 1 105 theme hyper-IgE 235:243 arg1 HIES 255:258 HIES 255:258 HIES 255:258 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 24698316 1 105 theme hyper-IgE 235:243 arg1 syndrome 245:252 the hyper-IgE syndrome 231:252 the hyper-IgE syndrome (HIES) 231:259 BACKGROUND Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). 6714239 1 0 attach isolated 164:171 arg2 sialyloligosaccharides 136:157 Three phosphate-containing sialyloligosaccharides 109:157 Three phosphate-containing sialyloligosaccharides 109:157 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 1 0 attach isolated 164:171 arg1 urine 191:195 normal human urine 178:195 normal human urine 178:195 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 4 1 theme sialyloligosaccharide 871:891 arg1 glycolipids 925:935 glycolipids 925:935 glycolipids 925:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 1 theme sialyloligosaccharide 871:891 arg1 glycoproteins 907:919 glycoproteins 907:919 glycoproteins 907:919 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 1 theme sialyloligosaccharide 871:891 arg1 groups 897:902 the common sialyloligosaccharide end groups 860:902 the common sialyloligosaccharide end groups of glycoproteins and glycolipids 860:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 1 2 theme charcoal 203:210 arg1 chromatography 239:252 charcoal adsorption, gel-filtration chromatography 203:252 chromatography 239:252 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 1 2 theme charcoal 203:210 arg1 chromatography 268:281 ion-exchange chromatography 255:281 ion-exchange chromatography 255:281 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 1 2 theme charcoal 203:210 arg1 chromatography 293:306 paper chromatography 287:306 paper chromatography 287:306 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 2 3 theme Gal 604:606 arg1 -P 630:631 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P 588:631 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 5 4 from excretion 942:950 arg1 urine 987:991 normal human urine 974:991 normal human urine 974:991 The excretion of these compounds in normal human urine may indicate the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates. 6714239 2 5 theme beta 654:657 arg1 -P 676:677 NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P 634:677 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 6 theme NeuAc 680:684 arg1 -P 722:723 NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 680:723 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 1 7 theme adsorption 212:221 arg1 chromatography 239:252 charcoal adsorption, gel-filtration chromatography 203:252 chromatography 239:252 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 1 7 theme adsorption 212:221 arg1 chromatography 268:281 ion-exchange chromatography 255:281 ion-exchange chromatography 255:281 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 1 7 theme adsorption 212:221 arg1 chromatography 293:306 paper chromatography 287:306 paper chromatography 287:306 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 4 8 with identical 845:853 arg1 glycolipids 925:935 glycolipids 925:935 glycolipids 925:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 8 with identical 845:853 arg1 glycoproteins 907:919 glycoproteins 907:919 glycoproteins 907:919 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 8 with identical 845:853 arg1 groups 897:902 the common sialyloligosaccharide end groups 860:902 the common sialyloligosaccharide end groups of glycoproteins and glycolipids 860:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 2 9 theme alpha 624:628 arg1 -P 630:631 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P 588:631 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 5 10 theme novel 1025:1029 arg1 pathway 1050:1056 a novel, as yet unrevealed pathway 1023:1056 a novel, as yet unrevealed pathway 1023:1056 The excretion of these compounds in normal human urine may indicate the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates. 6714239 4 11 theme glycolipids 925:935 arg1 glycolipids 925:935 glycolipids 925:935 glycolipids 925:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 11 theme glycolipids 925:935 arg1 glycoproteins 907:919 glycoproteins 907:919 glycoproteins 907:919 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 11 theme glycolipids 925:935 arg1 groups 897:902 the common sialyloligosaccharide end groups 860:902 the common sialyloligosaccharide end groups of glycoproteins and glycolipids 860:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 5 12 theme human 981:985 arg1 urine 987:991 normal human urine 974:991 normal human urine 974:991 The excretion of these compounds in normal human urine may indicate the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates. 6714239 5 13 theme carbohydrates 1087:1099 arg1 metabolism 1065:1074 the metabolism 1061:1074 the metabolism of complex carbohydrates 1061:1099 The excretion of these compounds in normal human urine may indicate the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates. 6714239 4 14 theme common 864:869 arg1 glycolipids 925:935 glycolipids 925:935 glycolipids 925:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 14 theme common 864:869 arg1 glycoproteins 907:919 glycoproteins 907:919 glycoproteins 907:919 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 14 theme common 864:869 arg1 groups 897:902 the common sialyloligosaccharide end groups 860:902 the common sialyloligosaccharide end groups of glycoproteins and glycolipids 860:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 2 15 theme Gal 650:652 arg1 -P 676:677 NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P 634:677 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 16 theme glycosidase 480:490 arg1 treatments 508:517 glycosidase and phosphatase treatments 480:517 treatments 508:517 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 17 theme determination 433:445 arg1 chromatography 338:351 gas-liquid chromatography 327:351 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments 327:517 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 18 theme GlcNAc 617:622 arg1 -P 630:631 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P 588:631 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 19 theme alpha 670:674 arg1 -P 676:677 NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P 634:677 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 20 theme disaccharide 375:386 arg1 derivatives 388:398 disaccharide derivatives 375:398 disaccharide derivatives 375:398 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 21 theme following 533:541 arg1 structures 549:558 the following three structures 529:558 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 5 22 theme normal 974:979 arg1 urine 987:991 normal human urine 974:991 normal human urine 974:991 The excretion of these compounds in normal human urine may indicate the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates. 6714239 2 23 theme NeuAc 588:592 arg1 -P 630:631 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P 588:631 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 24 theme GlcNAc 663:668 arg1 -P 676:677 NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P 634:677 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 25 theme 2-3 692:694 arg1 -P 722:723 NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 680:723 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 26 theme phosphate 423:431 arg1 determination 433:445 phosphate determination 423:445 phosphate determination 423:445 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 5 27 from existence 1010:1018 arg1 metabolism 1065:1074 the metabolism 1061:1074 the metabolism of complex carbohydrates 1061:1099 The excretion of these compounds in normal human urine may indicate the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates. 6714239 5 28 dep novel 1025:1029 arg1 unrevealed 1039:1048 unrevealed 1039:1048 unrevealed 1039:1048 The excretion of these compounds in normal human urine may indicate the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates. 6714239 2 29 theme alpha 686:690 arg1 -P 722:723 NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 680:723 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 1 30 theme phosphate-containing 115:134 arg1 sialyloligosaccharides 136:157 Three phosphate-containing sialyloligosaccharides 109:157 Three phosphate-containing sialyloligosaccharides 109:157 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 2 31 theme treatments 508:517 arg1 chromatography 338:351 gas-liquid chromatography 327:351 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments 327:517 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 32 theme NeuAc 634:638 arg1 -P 676:677 NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P 634:677 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 33 theme analysis 413:420 arg1 chromatography 338:351 gas-liquid chromatography 327:351 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments 327:517 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 34 dep structures 549:558 arg1 -P 630:631 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P 588:631 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 34 dep structures 549:558 arg1 -P 722:723 NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 680:723 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 1 35 theme ion-exchange 255:266 arg1 chromatography 239:252 charcoal adsorption, gel-filtration chromatography 203:252 chromatography 239:252 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 1 35 theme ion-exchange 255:266 arg1 chromatography 268:281 ion-exchange chromatography 255:281 ion-exchange chromatography 255:281 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 5 36 theme compounds 961:969 arg1 excretion 942:950 The excretion 938:950 The excretion of these compounds in normal human urine 938:991 The excretion of these compounds in normal human urine may indicate the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates. 6714239 2 37 theme methylation 401:411 arg1 analysis 413:420 methylation analysis 401:420 methylation analysis 401:420 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 38 theme derivatives 388:398 arg1 chromatography 338:351 gas-liquid chromatography 327:351 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments 327:517 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 0 39 theme phosphate-containing 40:59 arg1 characterization 14:29 characterization 14:29 characterization 14:29 Isolation and characterization of novel phosphate-containing sialyloligosaccharides from normal human urine. 6714239 0 39 theme phosphate-containing 40:59 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and characterization of novel phosphate-containing sialyloligosaccharides from normal human urine. 6714239 1 40 dep chromatography 239:252 arg1 gel-filtration 224:237 charcoal adsorption, gel-filtration chromatography 203:252 gel-filtration 224:237 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 0 41 theme novel 34:38 arg1 phosphate-containing 40:59 novel phosphate-containing 34:59 novel phosphate-containing 34:59 Isolation and characterization of novel phosphate-containing sialyloligosaccharides from normal human urine. 6714239 5 42 theme complex 1079:1085 arg1 carbohydrates 1087:1099 complex carbohydrates 1079:1099 complex carbohydrates 1079:1099 The excretion of these compounds in normal human urine may indicate the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates. 6714239 1 43 theme paper 287:291 arg1 chromatography 239:252 charcoal adsorption, gel-filtration chromatography 203:252 chromatography 239:252 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 1 43 theme paper 287:291 arg1 chromatography 293:306 paper chromatography 287:306 paper chromatography 287:306 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 2 44 theme alpha 594:598 arg1 -P 630:631 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P 588:631 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 45 dep -P 630:631 arg1 -P 676:677 NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P 634:677 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 4 46 theme glycoproteins 907:919 arg1 glycolipids 925:935 glycolipids 925:935 glycolipids 925:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 46 theme glycoproteins 907:919 arg1 glycoproteins 907:919 glycoproteins 907:919 glycoproteins 907:919 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 46 theme glycoproteins 907:919 arg1 groups 897:902 the common sialyloligosaccharide end groups 860:902 the common sialyloligosaccharide end groups of glycoproteins and glycolipids 860:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 2 47 theme beta 608:611 arg1 -P 630:631 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P 588:631 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 48 theme beta 700:703 arg1 -P 722:723 NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 680:723 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 49 theme chromatography 461:474 arg1 chromatography 338:351 gas-liquid chromatography 327:351 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments 327:517 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 3 50 theme sialyloligosaccharide 732:752 arg1 1-phosphates 754:765 These sialyloligosaccharide 1-phosphates 726:765 These sialyloligosaccharide 1-phosphates 726:765 These sialyloligosaccharide 1-phosphates represent a novel class of oligosaccharides. 6714239 2 51 theme 2-3 646:648 arg1 -P 676:677 NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P 634:677 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 4 52 theme oligosaccharide 818:832 arg1 chains 834:839 Their oligosaccharide chains 812:839 Their oligosaccharide chains 812:839 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 2 53 theme ion-exchange 448:459 arg1 chromatography 461:474 ion-exchange chromatography 448:474 ion-exchange chromatography 448:474 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 54 theme alpha 640:644 arg1 -P 676:677 NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P 634:677 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 5 55 theme pathway 1050:1056 arg1 existence 1010:1018 the existence 1006:1018 the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates 1006:1099 The excretion of these compounds in normal human urine may indicate the existence of a novel, as yet unrevealed pathway in the metabolism of complex carbohydrates. 6714239 2 56 theme monosaccharide 356:369 arg1 chromatography 338:351 gas-liquid chromatography 327:351 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments 327:517 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 57 theme Gal 696:698 arg1 -P 722:723 NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 680:723 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 1 58 theme normal 178:183 arg1 urine 191:195 normal human urine 178:195 normal human urine 178:195 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 2 59 theme alpha 716:720 arg1 -P 722:723 NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 680:723 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 1 60 theme human 185:189 arg1 urine 191:195 normal human urine 178:195 normal human urine 178:195 Three phosphate-containing sialyloligosaccharides were isolated from normal human urine using charcoal adsorption, gel-filtration chromatography, ion-exchange chromatography and paper chromatography. 6714239 4 61 theme end 893:895 arg1 glycolipids 925:935 glycolipids 925:935 glycolipids 925:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 61 theme end 893:895 arg1 glycoproteins 907:919 glycoproteins 907:919 glycoproteins 907:919 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 4 61 theme end 893:895 arg1 groups 897:902 the common sialyloligosaccharide end groups 860:902 the common sialyloligosaccharide end groups of glycoproteins and glycolipids 860:935 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 6714239 3 62 theme oligosaccharides 794:809 arg1 class 785:789 a novel class 777:789 a novel class of oligosaccharides 777:809 These sialyloligosaccharide 1-phosphates represent a novel class of oligosaccharides. 6714239 0 63 theme human 96:100 arg1 urine 102:106 normal human urine 89:106 normal human urine 89:106 Isolation and characterization of novel phosphate-containing sialyloligosaccharides from normal human urine. 6714239 2 64 theme phosphatase 496:506 arg1 treatments 508:517 glycosidase and phosphatase treatments 480:517 treatments 508:517 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 3 65 theme novel 779:783 arg1 class 785:789 a novel class 777:789 a novel class of oligosaccharides 777:809 These sialyloligosaccharide 1-phosphates represent a novel class of oligosaccharides. 6714239 0 66 theme normal 89:94 arg1 urine 102:106 normal human urine 89:106 normal human urine 89:106 Isolation and characterization of novel phosphate-containing sialyloligosaccharides from normal human urine. 6714239 2 67 theme gas-liquid 327:336 arg1 chromatography 338:351 gas-liquid chromatography 327:351 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments 327:517 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 2 68 theme GalNAc 709:714 arg1 -P 722:723 NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 680:723 the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P 529:723 Studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, phosphate determination, ion-exchange chromatography and glycosidase and phosphatase treatments indicated the following three structures for the compounds isolated: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(alpha)-P; NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc(alpha)-P. 6714239 4 69 gly glycoproteins 907:919 arg1 glycoproteins 907:919 glycoproteins 907:919 glycoproteins 907:919 Their oligosaccharide chains are identical with the common sialyloligosaccharide end groups of glycoproteins and glycolipids. 10918037 6 0 theme recombinant 1024:1034 arg1 L-selectin 1050:1059 recombinant soluble human L-selectin 1024:1059 recombinant soluble human L-selectin 1024:1059 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 6 1 gly fucosylated 1123:1133 arg1 tri- 1074:1077 tri- 1074:1077 tri- 1074:1077 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 6 1 gly fucosylated 1123:1133 arg1 bi- 1069:1071 bi- 1069:1071 bi- 1069:1071 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 6 1 gly fucosylated 1123:1133 arg1 chains 1105:1110 tetra-antennary sugar chains 1083:1110 tetra-antennary sugar chains 1083:1110 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 6 2 theme sugar 1099:1103 arg1 chains 1105:1110 tetra-antennary sugar chains 1083:1110 tetra-antennary sugar chains 1083:1110 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 0 3 theme kidney 92:97 arg1 cells 99:103 baby-hamster kidney cells 79:103 baby-hamster kidney cells 79:103 Carbohydrate structures of soluble human L-selectin recombinantly expressed in baby-hamster kidney cells. 10918037 4 4 theme N-glycans 563:571 arg1 Sialylation 544:554 Sialylation 544:554 Sialylation of the N-glycans 544:571 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 7 5 theme sialic 1198:1203 arg1 residues 1210:1217 sialic acid residues 1198:1217 sialic acid residues linked to these glycans 1198:1241 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 2 6 theme L-selectin 364:373 arg1 structures 336:345 the oligosaccharide structures 316:345 the oligosaccharide structures of soluble human L-selectin, recombinantly expressed in baby-hamster kidney cells, 316:428 In the present study the oligosaccharide structures of soluble human L-selectin, recombinantly expressed in baby-hamster kidney cells, were determined. 10918037 10 7 gly O-Glycosylation 1554:1568 arg1 L-selectin 1643:1652 recombinant soluble human L-selectin 1617:1652 recombinant soluble human L-selectin 1617:1652 O-Glycosylation of mucin-type sugar chains was not detected in recombinant soluble human L-selectin. 10918037 10 7 gly O-Glycosylation 1554:1568 arg1 chains 1590:1595 mucin-type sugar chains 1573:1595 mucin-type sugar chains 1573:1595 O-Glycosylation of mucin-type sugar chains was not detected in recombinant soluble human L-selectin. 10918037 4 8 from fractions 665:673 arg1 HPLC 690:693 amino-phase HPLC 678:693 amino-phase HPLC after release of the sialic acid residues 678:735 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 1 9 theme leucocyte 263:271 arg1 adhesion 285:292 leucocyte endothelium adhesion 263:292 leucocyte endothelium adhesion 263:292 A soluble form of L-selectin was recombinantly produced, which might be an effective therapeutic agent in inflammatory disorders, acting as an inhibitor for leucocyte endothelium adhesion. 10918037 7 10 theme tetrasialylated 1281:1295 arg1 oligosaccharides 1297:1312 tetrasialylated oligosaccharides 1281:1312 tetrasialylated oligosaccharides 1281:1312 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 7 10 theme tetrasialylated 1281:1295 arg1 4 1278:1278 4 1278:1278 4 1278:1278 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 5 11 theme Desialylated 738:749 arg1 oligosaccharides 751:766 Desialylated oligosaccharides 738:766 Desialylated oligosaccharides 738:766 Desialylated oligosaccharides were separated using two-dimensional HPLC and characterized by digestion with exoglycosidases and MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein were determined. 10918037 7 12 dep 0 1255:1255 arg1 oligosaccharides 1297:1312 tetrasialylated oligosaccharides 1281:1312 tetrasialylated oligosaccharides 1281:1312 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 7 12 dep 0 1255:1255 arg1 to 1275:1276 to 1275:1276 to 1275:1276 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 7 12 dep 0 1255:1255 arg1 4 1278:1278 4 1278:1278 4 1278:1278 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 9 13 theme blood-group 1508:1518 arg1 determinant 1520:1530 blood-group determinant 1508:1530 blood-group determinant 1508:1530 In addition to the main glycans, different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant were also identified. 10918037 1 14 theme endothelium 273:283 arg1 adhesion 285:292 leucocyte endothelium adhesion 263:292 leucocyte endothelium adhesion 263:292 A soluble form of L-selectin was recombinantly produced, which might be an effective therapeutic agent in inflammatory disorders, acting as an inhibitor for leucocyte endothelium adhesion. 10918037 5 15 theme overall 943:949 arg1 glycosylation 951:963 the overall glycosylation 939:963 the overall glycosylation of this protein 939:979 Desialylated oligosaccharides were separated using two-dimensional HPLC and characterized by digestion with exoglycosidases and MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein were determined. 10918037 9 16 dep N-acetylgalactosamine 1472:1492 arg1 determinant 1520:1530 blood-group determinant 1508:1530 blood-group determinant 1508:1530 In addition to the main glycans, different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant were also identified. 10918037 7 17 theme residues 1210:1217 arg1 number 1188:1193 The number 1184:1193 The number of sialic acid residues linked to these glycans 1184:1241 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 7 18 gly tetrasialylated 1281:1295 arg1 oligosaccharides 1297:1312 tetrasialylated oligosaccharides 1281:1312 tetrasialylated oligosaccharides 1281:1312 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 7 18 gly tetrasialylated 1281:1295 arg1 4 1278:1278 4 1278:1278 4 1278:1278 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 1 19 theme effective 181:189 arg1 which 163:167 which 163:167 which 163:167 A soluble form of L-selectin was recombinantly produced, which might be an effective therapeutic agent in inflammatory disorders, acting as an inhibitor for leucocyte endothelium adhesion. 10918037 1 19 theme effective 181:189 arg1 agent 203:207 an effective therapeutic agent 178:207 an effective therapeutic agent in inflammatory disorders 178:233 A soluble form of L-selectin was recombinantly produced, which might be an effective therapeutic agent in inflammatory disorders, acting as an inhibitor for leucocyte endothelium adhesion. 10918037 4 20 theme residues 728:735 arg1 release 701:707 release 701:707 release of the sialic acid residues 701:735 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 4 21 theme resulting 655:663 arg1 fractions 665:673 the resulting fractions 651:673 the resulting fractions on amino-phase HPLC after release of the sialic acid residues 651:735 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 3 22 link N-linked 451:458 arg1 glycans 460:466 The N-linked glycans 447:466 The N-linked glycans 447:466 The N-linked glycans were enzymically released and fluorescently labelled with 2-aminobenzamide. 10918037 10 23 theme sugar 1584:1588 arg1 chains 1590:1595 mucin-type sugar chains 1573:1595 mucin-type sugar chains 1573:1595 O-Glycosylation of mucin-type sugar chains was not detected in recombinant soluble human L-selectin. 10918037 5 24 gly Desialylated 738:749 arg1 oligosaccharides 751:766 Desialylated oligosaccharides 738:766 Desialylated oligosaccharides 738:766 Desialylated oligosaccharides were separated using two-dimensional HPLC and characterized by digestion with exoglycosidases and MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein were determined. 10918037 2 25 theme kidney 416:421 arg1 cells 423:427 baby-hamster kidney cells 403:427 baby-hamster kidney cells 403:427 In the present study the oligosaccharide structures of soluble human L-selectin, recombinantly expressed in baby-hamster kidney cells, were determined. 10918037 4 26 from rechromatography 631:646 arg1 HPLC 690:693 amino-phase HPLC 678:693 amino-phase HPLC after release of the sialic acid residues 678:735 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 9 27 theme minor 1435:1439 arg1 structures 1441:1450 different minor structures 1425:1450 different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant 1425:1530 In addition to the main glycans, different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant were also identified. 10918037 5 28 gly glycosylation 951:963 arg1 protein 973:979 this protein 968:979 this protein 968:979 Desialylated oligosaccharides were separated using two-dimensional HPLC and characterized by digestion with exoglycosidases and MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein were determined. 10918037 2 29 theme oligosaccharide 320:334 arg1 structures 336:345 the oligosaccharide structures 316:345 the oligosaccharide structures of soluble human L-selectin, recombinantly expressed in baby-hamster kidney cells, 316:428 In the present study the oligosaccharide structures of soluble human L-selectin, recombinantly expressed in baby-hamster kidney cells, were determined. 10918037 2 30 theme baby-hamster 403:414 arg1 cells 423:427 baby-hamster kidney cells 403:427 baby-hamster kidney cells 403:427 In the present study the oligosaccharide structures of soluble human L-selectin, recombinantly expressed in baby-hamster kidney cells, were determined. 10918037 0 31 theme Carbohydrate 0:11 arg1 structures 13:22 Carbohydrate structures 0:22 Carbohydrate structures of soluble human L-selectin 0:50 Carbohydrate structures of soluble human L-selectin recombinantly expressed in baby-hamster kidney cells. 10918037 6 32 theme tetra-antennary 1083:1097 arg1 chains 1105:1110 tetra-antennary sugar chains 1083:1110 tetra-antennary sugar chains 1083:1110 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 7 33 theme acid 1205:1208 arg1 residues 1210:1217 sialic acid residues 1198:1217 sialic acid residues linked to these glycans 1198:1241 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 9 34 theme terminal 1463:1470 arg1 N-acetylgalactosamine 1472:1492 terminal N-acetylgalactosamine 1463:1492 terminal N-acetylgalactosamine 1463:1492 In addition to the main glycans, different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant were also identified. 10918037 10 35 theme mucin-type 1573:1582 arg1 chains 1590:1595 mucin-type sugar chains 1573:1595 mucin-type sugar chains 1573:1595 O-Glycosylation of mucin-type sugar chains was not detected in recombinant soluble human L-selectin. 10918037 1 36 theme therapeutic 191:201 arg1 which 163:167 which 163:167 which 163:167 A soluble form of L-selectin was recombinantly produced, which might be an effective therapeutic agent in inflammatory disorders, acting as an inhibitor for leucocyte endothelium adhesion. 10918037 1 36 theme therapeutic 191:201 arg1 agent 203:207 an effective therapeutic agent 178:207 an effective therapeutic agent in inflammatory disorders 178:233 A soluble form of L-selectin was recombinantly produced, which might be an effective therapeutic agent in inflammatory disorders, acting as an inhibitor for leucocyte endothelium adhesion. 10918037 0 37 theme soluble 27:33 arg1 L-selectin 41:50 soluble human L-selectin 27:50 soluble human L-selectin 27:50 Carbohydrate structures of soluble human L-selectin recombinantly expressed in baby-hamster kidney cells. 10918037 5 38 theme two-dimensional 789:803 arg1 HPLC 805:808 two-dimensional HPLC 789:808 two-dimensional HPLC 789:808 Desialylated oligosaccharides were separated using two-dimensional HPLC and characterized by digestion with exoglycosidases and MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein were determined. 10918037 1 39 theme soluble 108:114 arg1 form 116:119 A soluble form 106:119 A soluble form of L-selectin 106:133 A soluble form of L-selectin was recombinantly produced, which might be an effective therapeutic agent in inflammatory disorders, acting as an inhibitor for leucocyte endothelium adhesion. 10918037 6 40 theme N-acetylglucosamine 1163:1181 arg1 N-acetylglucosamine 1163:1181 N-acetylglucosamine 1163:1181 N-acetylglucosamine 1163:1181 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 6 40 theme N-acetylglucosamine 1163:1181 arg1 residue 1152:1158 the innermost residue 1138:1158 the innermost residue of N-acetylglucosamine 1138:1181 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 9 41 theme different 1425:1433 arg1 structures 1441:1450 different minor structures 1425:1450 different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant 1425:1530 In addition to the main glycans, different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant were also identified. 10918037 2 42 theme present 302:308 arg1 study 310:314 the present study 298:314 the present study 298:314 In the present study the oligosaccharide structures of soluble human L-selectin, recombinantly expressed in baby-hamster kidney cells, were determined. 10918037 7 43 theme neutral 1258:1264 arg1 0 1255:1255 0 1255:1255 0 1255:1255 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 7 43 theme neutral 1258:1264 arg1 glycans 1266:1272 neutral glycans 1258:1272 neutral glycans 1258:1272 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 0 44 theme L-selectin 41:50 arg1 structures 13:22 Carbohydrate structures 0:22 Carbohydrate structures of soluble human L-selectin 0:50 Carbohydrate structures of soluble human L-selectin recombinantly expressed in baby-hamster kidney cells. 10918037 2 45 theme soluble 350:356 arg1 L-selectin 364:373 soluble human L-selectin 350:373 soluble human L-selectin 350:373 In the present study the oligosaccharide structures of soluble human L-selectin, recombinantly expressed in baby-hamster kidney cells, were determined. 10918037 10 46 theme chains 1590:1595 arg1 O-Glycosylation 1554:1568 O-Glycosylation 1554:1568 O-Glycosylation of mucin-type sugar chains 1554:1595 O-Glycosylation of mucin-type sugar chains was not detected in recombinant soluble human L-selectin. 10918037 4 47 theme sialic 716:721 arg1 residues 728:735 the sialic acid residues 712:735 the sialic acid residues 712:735 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 3 48 theme N-linked 451:458 arg1 glycans 460:466 The N-linked glycans 447:466 The N-linked glycans 447:466 The N-linked glycans were enzymically released and fluorescently labelled with 2-aminobenzamide. 10918037 1 49 theme inflammatory 212:223 arg1 disorders 225:233 inflammatory disorders 212:233 inflammatory disorders 212:233 A soluble form of L-selectin was recombinantly produced, which might be an effective therapeutic agent in inflammatory disorders, acting as an inhibitor for leucocyte endothelium adhesion. 10918037 0 50 theme human 35:39 arg1 L-selectin 41:50 soluble human L-selectin 27:50 soluble human L-selectin 27:50 Carbohydrate structures of soluble human L-selectin recombinantly expressed in baby-hamster kidney cells. 10918037 5 51 theme oligosaccharide 883:897 arg1 structures 899:908 More than 30 oligosaccharide structures 870:908 MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein 866:979 Desialylated oligosaccharides were separated using two-dimensional HPLC and characterized by digestion with exoglycosidases and MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein were determined. 10918037 5 52 theme glycosylation 951:963 arg1 structures 899:908 More than 30 oligosaccharide structures 870:908 MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein 866:979 Desialylated oligosaccharides were separated using two-dimensional HPLC and characterized by digestion with exoglycosidases and MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein were determined. 10918037 5 53 theme protein 973:979 arg1 glycosylation 951:963 the overall glycosylation 939:963 the overall glycosylation of this protein 939:979 Desialylated oligosaccharides were separated using two-dimensional HPLC and characterized by digestion with exoglycosidases and MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein were determined. 10918037 10 54 theme soluble 1629:1635 arg1 L-selectin 1643:1652 recombinant soluble human L-selectin 1617:1652 recombinant soluble human L-selectin 1617:1652 O-Glycosylation of mucin-type sugar chains was not detected in recombinant soluble human L-selectin. 10918037 4 55 from HPLC 690:693 arg1 rechromatography 631:646 rechromatography 631:646 rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues 631:735 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 2 56 theme human 358:362 arg1 L-selectin 364:373 soluble human L-selectin 350:373 soluble human L-selectin 350:373 In the present study the oligosaccharide structures of soluble human L-selectin, recombinantly expressed in baby-hamster kidney cells, were determined. 10918037 8 57 theme sialic 1320:1325 arg1 acid 1327:1330 The sialic acid 1316:1330 The sialic acid 1316:1330 The sialic acid is found exclusively in the alpha 2-3 linkage to galactose. 10918037 4 58 theme anion-exchange 589:602 arg1 chromatography 604:617 anion-exchange chromatography 589:617 anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues 589:735 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 10 59 theme recombinant 1617:1627 arg1 L-selectin 1643:1652 recombinant soluble human L-selectin 1617:1652 recombinant soluble human L-selectin 1617:1652 O-Glycosylation of mucin-type sugar chains was not detected in recombinant soluble human L-selectin. 10918037 5 60 with digestion 831:839 arg1 exoglycosidases 846:860 exoglycosidases 846:860 exoglycosidases 846:860 Desialylated oligosaccharides were separated using two-dimensional HPLC and characterized by digestion with exoglycosidases and MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein were determined. 10918037 1 61 from agent 203:207 arg1 disorders 225:233 inflammatory disorders 212:233 inflammatory disorders 212:233 A soluble form of L-selectin was recombinantly produced, which might be an effective therapeutic agent in inflammatory disorders, acting as an inhibitor for leucocyte endothelium adhesion. 10918037 1 62 theme L-selectin 124:133 arg1 form 116:119 A soluble form 106:119 A soluble form of L-selectin 106:133 A soluble form of L-selectin was recombinantly produced, which might be an effective therapeutic agent in inflammatory disorders, acting as an inhibitor for leucocyte endothelium adhesion. 10918037 7 63 attach linked 1219:1224 arg1 glycans 1235:1241 these glycans 1229:1241 these glycans 1229:1241 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 7 63 attach linked 1219:1224 arg2 residues 1210:1217 sialic acid residues 1198:1217 sialic acid residues linked to these glycans 1198:1241 The number of sialic acid residues linked to these glycans ranges from 0 (neutral glycans) to 4 (tetrasialylated oligosaccharides). 10918037 6 64 theme human 1044:1048 arg1 L-selectin 1050:1059 recombinant soluble human L-selectin 1024:1059 recombinant soluble human L-selectin 1024:1059 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 5 65 theme MS. 866:868 arg1 structures 899:908 More than 30 oligosaccharide structures 870:908 MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein 866:979 Desialylated oligosaccharides were separated using two-dimensional HPLC and characterized by digestion with exoglycosidases and MS. More than 30 oligosaccharide structures representing at least 95% of the overall glycosylation of this protein were determined. 10918037 10 66 located detected 1605:1612 arg2 O-Glycosylation 1554:1568 O-Glycosylation 1554:1568 O-Glycosylation of mucin-type sugar chains 1554:1595 O-Glycosylation of mucin-type sugar chains was not detected in recombinant soluble human L-selectin. 10918037 10 66 located detected 1605:1612 arg1 L-selectin 1643:1652 recombinant soluble human L-selectin 1617:1652 recombinant soluble human L-selectin 1617:1652 O-Glycosylation of mucin-type sugar chains was not detected in recombinant soluble human L-selectin. 10918037 8 67 theme 2-3 1366:1368 arg1 linkage 1370:1376 the alpha 2-3 linkage 1356:1376 the alpha 2-3 linkage to galactose 1356:1389 The sialic acid is found exclusively in the alpha 2-3 linkage to galactose. 10918037 4 68 theme amino-phase 678:688 arg1 HPLC 690:693 amino-phase HPLC 678:693 amino-phase HPLC after release of the sialic acid residues 678:735 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 0 69 theme baby-hamster 79:90 arg1 cells 99:103 baby-hamster kidney cells 79:103 baby-hamster kidney cells 79:103 Carbohydrate structures of soluble human L-selectin recombinantly expressed in baby-hamster kidney cells. 10918037 6 70 theme innermost 1142:1150 arg1 N-acetylglucosamine 1163:1181 N-acetylglucosamine 1163:1181 N-acetylglucosamine 1163:1181 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 6 70 theme innermost 1142:1150 arg1 residue 1152:1158 the innermost residue 1138:1158 the innermost residue of N-acetylglucosamine 1138:1181 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 6 71 contain carries 1061:1067 arg2 tri- 1074:1077 tri- 1074:1077 tri- 1074:1077 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 6 71 contain carries 1061:1067 arg2 bi- 1069:1071 bi- 1069:1071 bi- 1069:1071 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 6 71 contain carries 1061:1067 arg1 L-selectin 1050:1059 recombinant soluble human L-selectin 1024:1059 recombinant soluble human L-selectin 1024:1059 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 6 71 contain carries 1061:1067 arg2 chains 1105:1110 tetra-antennary sugar chains 1083:1110 tetra-antennary sugar chains 1083:1110 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 8 72 theme alpha 1360:1364 arg1 linkage 1370:1376 the alpha 2-3 linkage 1356:1376 the alpha 2-3 linkage to galactose 1356:1389 The sialic acid is found exclusively in the alpha 2-3 linkage to galactose. 10918037 10 73 theme human 1637:1641 arg1 L-selectin 1643:1652 recombinant soluble human L-selectin 1617:1652 recombinant soluble human L-selectin 1617:1652 O-Glycosylation of mucin-type sugar chains was not detected in recombinant soluble human L-selectin. 10918037 4 74 theme acid 723:726 arg1 residues 728:735 the sialic acid residues 712:735 the sialic acid residues 712:735 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 8 75 located found 1335:1339 arg2 acid 1327:1330 The sialic acid 1316:1330 The sialic acid 1316:1330 The sialic acid is found exclusively in the alpha 2-3 linkage to galactose. 10918037 8 75 located found 1335:1339 arg1 linkage 1370:1376 the alpha 2-3 linkage 1356:1376 the alpha 2-3 linkage to galactose 1356:1389 The sialic acid is found exclusively in the alpha 2-3 linkage to galactose. 10918037 4 76 theme fractions 665:673 arg1 rechromatography 631:646 rechromatography 631:646 rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues 631:735 Sialylation of the N-glycans was analysed by anion-exchange chromatography followed by rechromatography of the resulting fractions on amino-phase HPLC after release of the sialic acid residues. 10918037 6 77 theme soluble 1036:1042 arg1 L-selectin 1050:1059 recombinant soluble human L-selectin 1024:1059 recombinant soluble human L-selectin 1024:1059 The results revealed that recombinant soluble human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are fucosylated on the innermost residue of N-acetylglucosamine. 10918037 9 78 contain containing 1452:1461 arg2 N-acetylgalactosamine 1472:1492 terminal N-acetylgalactosamine 1463:1492 terminal N-acetylgalactosamine 1463:1492 In addition to the main glycans, different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant were also identified. 10918037 9 78 contain containing 1452:1461 arg2 O 1505:1505 O 1505:1505 O 1505:1505 In addition to the main glycans, different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant were also identified. 10918037 9 78 contain containing 1452:1461 arg2 H 1502:1502 the H 1498:1502 the H (O) 1498:1506 In addition to the main glycans, different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant were also identified. 10918037 9 78 contain containing 1452:1461 arg1 structures 1441:1450 different minor structures 1425:1450 different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant 1425:1530 In addition to the main glycans, different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant were also identified. 10918037 9 79 theme main 1411:1414 arg1 glycans 1416:1422 the main glycans 1407:1422 the main glycans 1407:1422 In addition to the main glycans, different minor structures containing terminal N-acetylgalactosamine, or the H (O) blood-group determinant were also identified. 2605230 0 0 from oligosaccharides 12:27 arg1 milk 68:71 human milk 62:71 human milk 62:71 Three novel oligosaccharides with the sialyl-Lea structure in human milk: isolation by immunoaffinity chromatography. 2605230 2 1 theme high-performance 370:385 arg1 chromatography 394:407 high-performance liquid chromatography 370:407 high-performance liquid chromatography 370:407 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2605230 1 2 theme novel 161:165 arg1 oligosaccharides 167:182 three novel oligosaccharides 155:182 three novel oligosaccharides isolated from human milk 155:207 We have determined the structures of three novel oligosaccharides isolated from human milk using the monoclonal antibody MSW 113. 2605230 0 3 theme immunoaffinity 87:100 arg1 chromatography 102:115 immunoaffinity chromatography 87:115 immunoaffinity chromatography 87:115 Three novel oligosaccharides with the sialyl-Lea structure in human milk: isolation by immunoaffinity chromatography. 2605230 3 4 theme sialyl-Lea 628:637 arg1 hexasaccharide 639:652 sialyl-Lea hexasaccharide 628:652 sialyl-Lea hexasaccharide 628:652 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 2 5 theme affinity 288:295 arg1 chromatography 297:310 affinity chromatography 288:310 affinity chromatography 288:310 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2605230 1 6 theme oligosaccharides 167:182 arg1 structures 141:150 the structures 137:150 the structures of three novel oligosaccharides isolated from human milk 137:207 We have determined the structures of three novel oligosaccharides isolated from human milk using the monoclonal antibody MSW 113. 2605230 3 7 theme 1H 438:439 arg1 spectroscopy 445:456 500-MHz 1H NMR spectroscopy 430:456 500-MHz 1H NMR spectroscopy 430:456 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 8 theme atom 467:470 arg1 spectrometry 489:500 fast atom bombardment-mass spectrometry 462:500 fast atom bombardment-mass spectrometry 462:500 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 0 9 theme novel 6:10 arg1 oligosaccharides 12:27 Three novel oligosaccharides 0:27 Three novel oligosaccharides with the sialyl-Lea structure in human milk: isolation by immunoaffinity chromatography. 0:116 Three novel oligosaccharides with the sialyl-Lea structure in human milk: isolation by immunoaffinity chromatography. 2605230 3 10 theme spectroscopy 445:456 arg1 results 419:425 the results 415:425 the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry 415:500 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 1 11 theme human 198:202 arg1 milk 204:207 human milk 198:207 human milk 198:207 We have determined the structures of three novel oligosaccharides isolated from human milk using the monoclonal antibody MSW 113. 2605230 1 12 attach isolated 184:191 arg2 oligosaccharides 167:182 three novel oligosaccharides 155:182 three novel oligosaccharides isolated from human milk 155:207 We have determined the structures of three novel oligosaccharides isolated from human milk using the monoclonal antibody MSW 113. 2605230 1 12 attach isolated 184:191 arg1 milk 204:207 human milk 198:207 human milk 198:207 We have determined the structures of three novel oligosaccharides isolated from human milk using the monoclonal antibody MSW 113. 2605230 0 13 theme sialyl-Lea 38:47 arg1 structure 49:57 the sialyl-Lea structure 34:57 the sialyl-Lea structure 34:57 Three novel oligosaccharides with the sialyl-Lea structure in human milk: isolation by immunoaffinity chromatography. 2605230 3 14 theme bombardment-mass 472:487 arg1 spectrometry 489:500 fast atom bombardment-mass spectrometry 462:500 fast atom bombardment-mass spectrometry 462:500 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 15 theme NMR 441:443 arg1 spectroscopy 445:456 500-MHz 1H NMR spectroscopy 430:456 500-MHz 1H NMR spectroscopy 430:456 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 16 theme spectrometry 489:500 arg1 results 419:425 the results 415:425 the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry 415:500 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 1 17 theme monoclonal 219:228 arg1 antibody 230:237 the monoclonal antibody 215:237 the monoclonal antibody MSW 113 215:245 We have determined the structures of three novel oligosaccharides isolated from human milk using the monoclonal antibody MSW 113. 2605230 1 18 dep MSW 239:241 arg1 113 243:245 113 243:245 113 243:245 We have determined the structures of three novel oligosaccharides isolated from human milk using the monoclonal antibody MSW 113. 2605230 0 19 with oligosaccharides 12:27 arg1 structure 49:57 the sialyl-Lea structure 34:57 the sialyl-Lea structure 34:57 Three novel oligosaccharides with the sialyl-Lea structure in human milk: isolation by immunoaffinity chromatography. 2605230 3 20 dep see 549:551 arg1 formula 540:546 formula 540:546 formula 540:546 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 21 theme 500-MHz 430:436 arg1 spectroscopy 445:456 500-MHz 1H NMR spectroscopy 430:456 500-MHz 1H NMR spectroscopy 430:456 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 22 theme structure-directed 686:703 arg1 antibody 716:723 another sialyl-Lea structure-directed monoclonal antibody 667:723 another sialyl-Lea structure-directed monoclonal antibody 667:723 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 22 theme structure-directed 686:703 arg1 19-9 729:732 NS 19-9 726:732 NS 19-9 726:732 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 2 23 theme antibody 354:361 arg1 column 317:322 a column 315:322 a column of the immobilized monoclonal antibody 315:361 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2605230 3 24 theme fast 462:465 arg1 spectrometry 489:500 fast atom bombardment-mass spectrometry 462:500 fast atom bombardment-mass spectrometry 462:500 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 25 theme monoclonal 705:714 arg1 antibody 716:723 another sialyl-Lea structure-directed monoclonal antibody 667:723 another sialyl-Lea structure-directed monoclonal antibody 667:723 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 25 theme monoclonal 705:714 arg1 19-9 729:732 NS 19-9 726:732 NS 19-9 726:732 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 2 26 theme monoclonal 343:352 arg1 antibody 354:361 the immobilized monoclonal antibody 327:361 the immobilized monoclonal antibody 327:361 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2605230 0 27 dep oligosaccharides 12:27 arg1 isolation 74:82 isolation 74:82 Three novel oligosaccharides with the sialyl-Lea structure in human milk: isolation by immunoaffinity chromatography. 0:116 Three novel oligosaccharides with the sialyl-Lea structure in human milk: isolation by immunoaffinity chromatography. 2605230 2 28 theme immobilized 331:341 arg1 antibody 354:361 the immobilized monoclonal antibody 327:361 the immobilized monoclonal antibody 327:361 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2605230 1 29 theme MSW 239:241 arg1 antibody 230:237 the monoclonal antibody 215:237 the monoclonal antibody MSW 113 215:245 We have determined the structures of three novel oligosaccharides isolated from human milk using the monoclonal antibody MSW 113. 2605230 3 30 theme sialyl-Lea 675:684 arg1 antibody 716:723 another sialyl-Lea structure-directed monoclonal antibody 667:723 another sialyl-Lea structure-directed monoclonal antibody 667:723 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 30 theme sialyl-Lea 675:684 arg1 19-9 729:732 NS 19-9 726:732 NS 19-9 726:732 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 31 theme same 613:616 arg1 extent 618:623 nearly the same extent 602:623 nearly the same extent as sialyl-Lea hexasaccharide 602:652 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 32 dep oligosaccharides 565:580 arg1 bound 658:662 bound 658:662 bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly 658:745 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 32 dep oligosaccharides 565:580 arg1 bound 582:586 bound 582:586 bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide 582:652 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 0 33 theme human 62:66 arg1 milk 68:71 human milk 62:71 human milk 62:71 Three novel oligosaccharides with the sialyl-Lea structure in human milk: isolation by immunoaffinity chromatography. 2605230 3 34 theme NS 726:727 arg1 antibody 716:723 another sialyl-Lea structure-directed monoclonal antibody 667:723 another sialyl-Lea structure-directed monoclonal antibody 667:723 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 3 34 theme NS 726:727 arg1 19-9 729:732 NS 19-9 726:732 NS 19-9 726:732 From the results of 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, their structures were deduced to be (formula; see text) These oligosaccharides bound to MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but bound to another sialyl-Lea structure-directed monoclonal antibody, NS 19-9, only weakly. 2605230 2 35 theme liquid 387:392 arg1 chromatography 394:407 high-performance liquid chromatography 370:407 high-performance liquid chromatography 370:407 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2007125 1 0 from milk 154:157 arg1 structure 133:141 the sialyl-Lea structure 118:141 the sialyl-Lea structure from human milk 118:157 We have isolated four novel oligosaccharides with the sialyl-Lea structure from human milk using a monoclonal antibody, MSW 113. 2007125 2 1 theme immobilized 280:290 arg1 antibody 303:310 the immobilized monoclonal antibody 276:310 the immobilized monoclonal antibody 276:310 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2007125 3 2 theme structural 374:383 arg1 analyses 385:392 structural analyses 374:392 structural analyses 374:392 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 3 3 with consistent 528:537 arg1 structures 558:567 the following structures 544:567 the following structures 544:567 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 3 4 theme atom 435:438 arg1 spectrometry 457:468 fast atom bombardment mass spectrometry 430:468 fast atom bombardment mass spectrometry 430:468 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 0 5 from structure 43:51 arg1 milk 62:65 human milk 56:65 human milk 56:65 Novel oligosaccharides with the sialyl-Lea structure in human milk. 2007125 0 6 theme Novel 0:4 arg1 oligosaccharides 6:21 Novel oligosaccharides 0:21 Novel oligosaccharides with the sialyl-Lea structure in human milk 0:65 Novel oligosaccharides with the sialyl-Lea structure in human milk. 2007125 1 7 theme monoclonal 167:176 arg1 antibody 178:185 a monoclonal antibody 165:185 a monoclonal antibody 165:185 We have isolated four novel oligosaccharides with the sialyl-Lea structure from human milk using a monoclonal antibody, MSW 113. 2007125 1 7 theme monoclonal 167:176 arg1 MSW 188:190 MSW 113 188:194 MSW 113 188:194 We have isolated four novel oligosaccharides with the sialyl-Lea structure from human milk using a monoclonal antibody, MSW 113. 2007125 1 8 with oligosaccharides 96:111 arg1 structure 133:141 the sialyl-Lea structure 118:141 the sialyl-Lea structure from human milk 118:157 We have isolated four novel oligosaccharides with the sialyl-Lea structure from human milk using a monoclonal antibody, MSW 113. 2007125 3 9 dep spectroscopy 416:427 arg1 i.e. 395:398 i.e. 395:398 i.e. 395:398 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 3 10 theme fast 430:433 arg1 spectrometry 457:468 fast atom bombardment mass spectrometry 430:468 fast atom bombardment mass spectrometry 430:468 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 3 11 theme analyses 385:392 arg1 results 363:369 The results 359:369 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, 359:522 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 3 11 theme analyses 385:392 arg1 consistent 528:537 consistent 528:537 consistent 528:537 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 2 12 theme antibody 303:310 arg1 column 266:271 a column 264:271 a column of the immobilized monoclonal antibody 264:310 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2007125 2 13 theme monoclonal 292:301 arg1 antibody 303:310 the immobilized monoclonal antibody 276:310 the immobilized monoclonal antibody 276:310 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2007125 3 14 theme NMR 412:414 arg1 spectroscopy 416:427 500-MHz 1H NMR spectroscopy 401:427 500-MHz 1H NMR spectroscopy 401:427 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 3 15 theme mass 452:455 arg1 spectrometry 457:468 fast atom bombardment mass spectrometry 430:468 fast atom bombardment mass spectrometry 430:468 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 0 16 theme sialyl-Lea 32:41 arg1 structure 43:51 the sialyl-Lea structure 28:51 the sialyl-Lea structure in human milk 28:65 Novel oligosaccharides with the sialyl-Lea structure in human milk. 2007125 0 17 theme human 56:60 arg1 milk 62:65 human milk 56:65 human milk 56:65 Novel oligosaccharides with the sialyl-Lea structure in human milk. 2007125 3 18 theme specific 486:493 arg1 antibodies 512:521 specific anticarbohydrate antibodies 486:521 specific anticarbohydrate antibodies 486:521 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 3 19 theme 1H 409:410 arg1 spectroscopy 416:427 500-MHz 1H NMR spectroscopy 401:427 500-MHz 1H NMR spectroscopy 401:427 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 0 20 with oligosaccharides 6:21 arg1 structure 43:51 the sialyl-Lea structure 28:51 the sialyl-Lea structure in human milk 28:65 Novel oligosaccharides with the sialyl-Lea structure in human milk. 2007125 3 21 theme anticarbohydrate 495:510 arg1 antibodies 512:521 specific anticarbohydrate antibodies 486:521 specific anticarbohydrate antibodies 486:521 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 1 22 theme sialyl-Lea 122:131 arg1 structure 133:141 the sialyl-Lea structure 118:141 the sialyl-Lea structure from human milk 118:157 We have isolated four novel oligosaccharides with the sialyl-Lea structure from human milk using a monoclonal antibody, MSW 113. 2007125 1 23 theme novel 90:94 arg1 oligosaccharides 96:111 four novel oligosaccharides 85:111 four novel oligosaccharides with the sialyl-Lea structure from human milk 85:157 We have isolated four novel oligosaccharides with the sialyl-Lea structure from human milk using a monoclonal antibody, MSW 113. 2007125 3 24 theme following 548:556 arg1 structures 558:567 the following structures 544:567 the following structures 544:567 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 2 25 theme high-performance 319:334 arg1 chromatography 343:356 high-performance liquid chromatography 319:356 high-performance liquid chromatography 319:356 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2007125 2 26 theme liquid 336:341 arg1 chromatography 343:356 high-performance liquid chromatography 319:356 high-performance liquid chromatography 319:356 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2007125 3 27 theme bombardment 440:450 arg1 spectrometry 457:468 fast atom bombardment mass spectrometry 430:468 fast atom bombardment mass spectrometry 430:468 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 3 28 theme 500-MHz 401:407 arg1 spectroscopy 416:427 500-MHz 1H NMR spectroscopy 401:427 500-MHz 1H NMR spectroscopy 401:427 The results of structural analyses, i.e., 500-MHz 1H NMR spectroscopy, fast atom bombardment mass spectrometry, and binding to specific anticarbohydrate antibodies, are consistent with the following structures. 2007125 2 29 theme affinity 237:244 arg1 chromatography 246:259 affinity chromatography 237:259 affinity chromatography 237:259 These oligosaccharides were purified by affinity chromatography on a column of the immobilized monoclonal antibody and by high-performance liquid chromatography. 2007125 1 30 theme human 148:152 arg1 milk 154:157 human milk 148:157 human milk 148:157 We have isolated four novel oligosaccharides with the sialyl-Lea structure from human milk using a monoclonal antibody, MSW 113. 2059624 3 0 theme N289-linked 559:569 arg1 r-HPg 595:599 N289-linked glycosylation of [R561E]r-HPg 559:599 N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells 559:655 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 9 1 with consequence 2062:2072 arg1 construct 2141:2149 the recombinant baculovirus/HPg-cDNA construct 2104:2149 the recombinant baculovirus/HPg-cDNA construct 2104:2149 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 8 2 from dependency 1872:1881 arg1 r-HPg 1935:1939 r-HPg 1935:1939 r-HPg 1935:1939 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 2 3 link N-linked 419:426 arg1 oligosaccharides 441:456 N-linked complex-type oligosaccharides 419:456 N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg) 419:507 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 6 4 theme various 1459:1465 arg1 levels 1467:1472 various levels 1459:1472 various levels of branching and outer arm completion 1459:1510 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 0 5 link Asparagine-linked 0:16 arg1 processing 34:43 Asparagine-linked oligosaccharide processing 0:43 Asparagine-linked oligosaccharide processing in lepidopteran insect cells 0:72 Asparagine-linked oligosaccharide processing in lepidopteran insect cells. 2059624 1 6 theme baculovirus 206:216 arg1 vector 218:223 baculovirus vector 206:223 baculovirus vector 206:223 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 4 7 contain containing 1039:1048 arg1 structures 1027:1036 such structures 1022:1036 such structures 1022:1036 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 4 7 contain containing 1039:1048 arg2 units 1062:1066 3-9 mannose units 1050:1066 3-9 mannose units 1050:1066 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 9 8 theme recombinant 2108:2118 arg1 construct 2141:2149 the recombinant baculovirus/HPg-cDNA construct 2104:2149 the recombinant baculovirus/HPg-cDNA construct 2104:2149 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 1 9 theme infected 225:232 arg1 cells 271:275 baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells 206:275 baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells 206:275 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 6 10 with glycans 1445:1451 arg1 levels 1467:1472 various levels 1459:1472 various levels of branching and outer arm completion 1459:1510 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 2 11 theme insect 351:356 arg1 cells 358:362 lepidopteran insect cells 338:362 lepidopteran insect cells 338:362 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 1 12 theme frugiperda 245:254 arg1 cells 271:275 baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells 206:275 baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells 206:275 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 4 13 theme r-HPg 947:951 arg1 N289 925:928 N289 925:928 N289 of the expressed r-HPg 925:951 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 5 14 theme time 1074:1077 arg1 window 1079:1084 a time window 1072:1084 a time window of 60-96 h, p.i. 1072:1101 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 6 15 theme glycans 1590:1596 arg1 % 1581:1581 approximately 23% 1565:1581 approximately 23% of the glycans 1565:1596 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 15 theme glycans 1590:1596 arg1 glycans 1590:1596 the glycans 1586:1596 the glycans 1586:1596 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 8 16 theme time 1867:1870 arg1 dependency 1872:1881 The time dependency 1863:1881 The time dependency of the assembly of complex-type oligosaccharides on r-HPg 1863:1939 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 6 17 theme arm 1497:1499 arg1 completion 1501:1510 outer arm completion 1491:1510 outer arm completion 1491:1510 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 4 18 theme earliest 780:787 arg1 p.i. 804:807 p.i. 804:807 p.i. 804:807 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 4 18 theme earliest 780:787 arg1 postinfection 789:801 the earliest postinfection 776:801 the earliest postinfection (p.i.) time period studied 776:828 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 9 19 theme glycosylation 2174:2186 arg1 characteristics 2188:2202 the normal glycosylation characteristics 2163:2202 the normal glycosylation characteristics of insect cells 2163:2218 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 3 20 theme r-HPg 595:599 arg1 nature 549:554 the nature 545:554 the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells 545:655 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 3 20 theme r-HPg 595:599 arg1 dependent 660:668 dependent 660:668 dependent 660:668 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 4 21 attach released 889:896 arg2 oligosaccharides 872:887 the oligosaccharides 868:887 the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg 868:951 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 4 21 attach released 889:896 arg1 N289 925:928 N289 925:928 N289 of the expressed r-HPg 925:951 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 3 22 theme present 517:523 arg1 paper 525:529 the present paper 513:529 the present paper 513:529 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 5 23 theme tetraantennary 1232:1245 arg1 classes 1255:1261 the biantennary, triantennary, and tetraantennary complex classes 1197:1261 the biantennary, triantennary, and tetraantennary complex classes 1197:1261 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 6 24 theme time 1329:1332 arg1 window 1341:1346 an intermediate time period window 1313:1346 an intermediate time period window 1313:1346 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 24 theme time 1329:1332 arg1 p.i. 1361:1364 p.i. 1361:1364 p.i. 1361:1364 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 7 25 used utilized 1829:1836 arg2 transferases 1812:1823 these transferases 1806:1823 these transferases 1806:1823 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 1 26 theme human 176:180 arg1 plasminogen 182:192 recombinant human plasminogen 164:192 recombinant human plasminogen 164:192 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 0 27 from processing 34:43 arg1 cells 68:72 lepidopteran insect cells 48:72 lepidopteran insect cells 48:72 Asparagine-linked oligosaccharide processing in lepidopteran insect cells. 2059624 9 28 theme infective 2081:2089 arg1 process 2091:2097 the infective process 2077:2097 the infective process 2077:2097 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 9 29 theme cells 2214:2218 arg1 characteristics 2188:2202 the normal glycosylation characteristics 2163:2202 the normal glycosylation characteristics of insect cells 2163:2218 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 8 30 theme complex-type 1902:1913 arg1 oligosaccharides 1915:1930 complex-type oligosaccharides 1902:1930 complex-type oligosaccharides 1902:1930 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 6 31 theme r-HPg 1628:1632 arg1 N289 1616:1619 N289 1616:1619 N289 of the r-HPg produced 1616:1641 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 5 32 from window 1079:1084 arg1 classes 1255:1261 the biantennary, triantennary, and tetraantennary complex classes 1197:1261 the biantennary, triantennary, and tetraantennary complex classes 1197:1261 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 4 33 from period 815:820 arg1 type 978:981 the high-mannose type 961:981 the high-mannose type 961:981 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 4 34 theme high-mannose 965:976 arg1 type 978:981 the high-mannose type 961:981 the high-mannose type 961:981 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 2 35 theme recombinant 471:481 arg1 r-HPg 502:506 recombinant human plasminogen (r-HPg) 471:507 recombinant human plasminogen (r-HPg) 471:507 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 5 36 theme h 1095:1095 arg1 window 1079:1084 a time window 1072:1084 a time window of 60-96 h, p.i. 1072:1101 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 8 37 theme glycosyl 1989:1996 arg1 transferases 1998:2009 the appropriate glycosyl transferases 1973:2009 the appropriate glycosyl transferases 1973:2009 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 8 38 theme transferase 2018:2028 arg1 genes 2030:2034 transferase genes 2018:2034 transferase genes 2018:2034 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 4 39 theme structures 1027:1036 arg1 range 1013:1017 nearly the full range 997:1017 nearly the full range of such structures, containing 3-9 mannose units 997:1066 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 5 40 theme outer 1288:1292 arg1 completion 1298:1307 outer arm completion 1288:1307 outer arm completion 1288:1307 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 0 41 theme Asparagine-linked 0:16 arg1 processing 34:43 Asparagine-linked oligosaccharide processing 0:43 Asparagine-linked oligosaccharide processing in lepidopteran insect cells 0:72 Asparagine-linked oligosaccharide processing in lepidopteran insect cells. 2059624 6 42 theme high-mannose 1517:1528 arg1 type 1530:1533 high-mannose type 1517:1533 high-mannose type of oligosaccharides 1517:1553 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 2 43 theme r-HPg 502:506 arg1 Asn289 461:466 Asn289 461:466 Asn289 of recombinant human plasminogen (r-HPg) 461:507 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 6 44 theme h 1358:1358 arg1 window 1341:1346 an intermediate time period window 1313:1346 an intermediate time period window 1313:1346 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 44 theme h 1358:1358 arg1 p.i. 1361:1364 p.i. 1361:1364 p.i. 1361:1364 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 1 45 theme oligosaccharides 116:131 arg1 nature 102:107 the nature 98:107 the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen 98:192 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 2 46 from laboratory 305:314 arg1 studies 287:293 Previous studies 278:293 Previous studies from this laboratory 278:314 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 4 47 theme full 1008:1011 arg1 range 1013:1017 nearly the full range 997:1017 nearly the full range of such structures, containing 3-9 mannose units 997:1066 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 3 48 theme infection 697:705 arg1 time 689:692 time 689:692 time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct 689:770 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 2 49 theme plasminogen 489:499 arg1 r-HPg 502:506 recombinant human plasminogen (r-HPg) 471:507 recombinant human plasminogen (r-HPg) 471:507 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 0 50 theme lepidopteran 48:59 arg1 cells 68:72 lepidopteran insect cells 48:72 lepidopteran insect cells 48:72 Asparagine-linked oligosaccharide processing in lepidopteran insect cells. 2059624 8 51 theme appropriate 1977:1987 arg1 transferases 1998:2009 the appropriate glycosyl transferases 1973:2009 the appropriate glycosyl transferases 1973:2009 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 7 52 theme N-linked 1764:1771 arg1 oligosaccharide 1781:1795 N-linked complex oligosaccharide 1764:1795 N-linked complex oligosaccharide 1764:1795 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 3 53 theme time 689:692 arg1 length 679:684 the length 675:684 the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct 675:770 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 8 54 theme transferases 1998:2009 arg1 activation 1959:1968 an activation 1956:1968 an activation of the appropriate glycosyl transferases and/or transferase genes 1956:2034 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 2 55 contain possess 364:370 arg1 cells 358:362 lepidopteran insect cells 338:362 lepidopteran insect cells 338:362 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 2 55 contain possess 364:370 arg2 machinery 390:398 the glycosylation machinery 372:398 the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg) 372:507 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 5 56 theme completion 1298:1307 arg1 extents 1277:1283 varying extents 1269:1283 varying extents of outer arm completion 1269:1307 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 3 57 theme glycosylation 571:583 arg1 r-HPg 595:599 N289-linked glycosylation of [R561E]r-HPg 559:599 N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells 559:655 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 6 58 theme oligosaccharides 1393:1408 arg1 mixture 1369:1375 a mixture 1367:1375 a mixture 1367:1375 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 5 59 theme rHPg 1184:1187 arg1 N289 1176:1179 N289 1176:1179 N289 of rHPg 1176:1187 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 7 60 theme glycosyltransferase 1713:1731 arg1 genes 1733:1737 the glycosyltransferase genes 1709:1737 the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide 1709:1795 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 4 61 theme mannose 1054:1060 arg1 units 1062:1066 3-9 mannose units 1050:1066 3-9 mannose units 1050:1066 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 8 62 theme oligosaccharides 1915:1930 arg1 assembly 1890:1897 the assembly 1886:1897 the assembly of complex-type oligosaccharides on r-HPg 1886:1939 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 2 63 theme N-linked 419:426 arg1 oligosaccharides 441:456 N-linked complex-type oligosaccharides 419:456 N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg) 419:507 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 5 64 theme total 1156:1160 arg1 % 1147:1147 92% 1145:1147 92% of the total 1145:1160 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 5 64 theme total 1156:1160 arg1 total 1156:1160 total 1156:1160 total 1156:1160 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 8 65 from assembly 1890:1897 arg1 r-HPg 1935:1939 r-HPg 1935:1939 r-HPg 1935:1939 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 3 66 theme recombinant 729:739 arg1 construct 762:770 the recombinant baculovirus/HPg-cDNA construct 725:770 the recombinant baculovirus/HPg-cDNA construct 725:770 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 2 67 theme lepidopteran 338:349 arg1 cells 358:362 lepidopteran insect cells 338:362 lepidopteran insect cells 338:362 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 7 68 theme insect 1688:1693 arg1 cells 1695:1699 lepidopteran insect cells 1675:1699 lepidopteran insect cells 1675:1699 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 9 69 theme process 2091:2097 arg1 consequence 2062:2072 one consequence 2058:2072 one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct 2058:2149 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 3 70 theme [R561E 588:593 arg1 r-HPg 595:599 N289-linked glycosylation of [R561E]r-HPg 559:599 N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells 559:655 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 4 71 dep h 842:842 arg1 i.e. 831:834 i.e. 831:834 i.e. 831:834 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 7 72 link N-linked 1764:1771 arg1 oligosaccharide 1781:1795 N-linked complex oligosaccharide 1764:1795 N-linked complex oligosaccharide 1764:1795 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 3 73 theme frugiperda 625:634 arg1 cells 651:655 Spodoptera frugiperda (IPLB-SF-21AE) cells 614:655 Spodoptera frugiperda (IPLB-SF-21AE) cells 614:655 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 6 74 theme glycans 1445:1451 arg1 type 1530:1533 high-mannose type 1517:1533 high-mannose type of oligosaccharides 1517:1553 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 74 theme glycans 1445:1451 arg1 oligosaccharides 1538:1553 oligosaccharides 1538:1553 oligosaccharides 1538:1553 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 74 theme glycans 1445:1451 arg1 % 1436:1436 approximately 77% 1420:1436 approximately 77% of the glycans, with various levels of branching and outer arm completion, 1420:1511 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 74 theme glycans 1445:1451 arg1 glycans 1445:1451 the glycans 1441:1451 the glycans 1441:1451 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 2 75 from oligosaccharides 441:456 arg1 Asn289 461:466 Asn289 461:466 Asn289 of recombinant human plasminogen (r-HPg) 461:507 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 8 76 theme assembly 1890:1897 arg1 dependency 1872:1881 The time dependency 1863:1881 The time dependency of the assembly of complex-type oligosaccharides on r-HPg 1863:1939 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 9 77 theme baculovirus/HPg-cDNA 2120:2139 arg1 construct 2141:2149 the recombinant baculovirus/HPg-cDNA construct 2104:2149 the recombinant baculovirus/HPg-cDNA construct 2104:2149 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 1 78 theme Spodoptera 234:243 arg1 frugiperda 245:254 Spodoptera frugiperda 234:254 baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells 206:275 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 1 78 theme Spodoptera 234:243 arg1 IPLB-SF-21AE 257:268 IPLB-SF-21AE 257:268 IPLB-SF-21AE 257:268 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 3 79 link N289-linked 559:569 arg1 r-HPg 595:599 N289-linked glycosylation of [R561E]r-HPg 559:599 N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells 559:655 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 2 80 theme Previous 278:285 arg1 studies 287:293 Previous studies 278:293 Previous studies from this laboratory 278:314 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 3 81 with infection 697:705 arg1 construct 762:770 the recombinant baculovirus/HPg-cDNA construct 725:770 the recombinant baculovirus/HPg-cDNA construct 725:770 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 4 82 theme expressed 937:945 arg1 r-HPg 947:951 the expressed r-HPg 933:951 the expressed r-HPg 933:951 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 5 83 with classes 1255:1261 arg1 extents 1277:1283 varying extents 1269:1283 varying extents of outer arm completion 1269:1307 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 6 84 theme completion 1501:1510 arg1 levels 1467:1472 various levels 1459:1472 various levels of branching and outer arm completion 1459:1510 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 4 85 theme glycopeptidase 903:916 arg1 F 918:918 glycopeptidase F 903:918 glycopeptidase F 903:918 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 5 86 theme triantennary 1214:1225 arg1 classes 1255:1261 the biantennary, triantennary, and tetraantennary complex classes 1197:1261 the biantennary, triantennary, and tetraantennary complex classes 1197:1261 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 9 87 theme normal 2167:2172 arg1 characteristics 2188:2202 the normal glycosylation characteristics 2163:2202 the normal glycosylation characteristics of insect cells 2163:2218 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 6 88 theme outer 1491:1495 arg1 completion 1501:1510 outer arm completion 1491:1510 outer arm completion 1491:1510 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 8 89 from r-HPg 1935:1939 arg1 dependency 1872:1881 The time dependency 1863:1881 The time dependency of the assembly of complex-type oligosaccharides on r-HPg 1863:1939 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 6 90 theme period 1334:1339 arg1 window 1341:1346 an intermediate time period window 1313:1346 an intermediate time period window 1313:1346 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 90 theme period 1334:1339 arg1 p.i. 1361:1364 p.i. 1361:1364 p.i. 1361:1364 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 91 theme branching 1477:1485 arg1 levels 1467:1472 various levels 1459:1472 various levels of branching and outer arm completion 1459:1510 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 1 92 theme recombinant 164:174 arg1 plasminogen 182:192 recombinant human plasminogen 164:192 recombinant human plasminogen 164:192 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 9 93 theme insect 2207:2212 arg1 cells 2214:2218 insect cells 2207:2218 insect cells 2207:2218 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 6 94 theme intermediate 1316:1327 arg1 window 1341:1346 an intermediate time period window 1313:1346 an intermediate time period window 1313:1346 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 94 theme intermediate 1316:1327 arg1 p.i. 1361:1364 p.i. 1361:1364 p.i. 1361:1364 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 1 95 theme plasminogen 182:192 arg1 asparagine-289 146:159 asparagine-289 146:159 asparagine-289 of recombinant human plasminogen 146:192 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 5 96 theme biantennary 1201:1211 arg1 classes 1255:1261 the biantennary, triantennary, and tetraantennary complex classes 1197:1261 the biantennary, triantennary, and tetraantennary complex classes 1197:1261 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 1 97 theme Temporal 75:82 arg1 dependence 84:93 Temporal dependence 75:93 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen 75:192 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 3 98 theme Spodoptera 614:623 arg1 IPLB-SF-21AE 637:648 IPLB-SF-21AE 637:648 IPLB-SF-21AE 637:648 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 3 98 theme Spodoptera 614:623 arg1 frugiperda 625:634 Spodoptera frugiperda 614:634 Spodoptera frugiperda (IPLB-SF-21AE) cells 614:655 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 5 99 dep oligosaccharides 1127:1142 arg1 % 1147:1147 92% 1145:1147 92% of the total 1145:1160 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 5 99 dep oligosaccharides 1127:1142 arg1 total 1156:1160 total 1156:1160 total 1156:1160 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 4 100 theme time 810:813 arg1 period 815:820 the earliest postinfection (p.i.) time period 776:820 the earliest postinfection (p.i.) time period studied 776:828 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 5 101 theme varying 1269:1275 arg1 extents 1277:1283 varying extents 1269:1283 varying extents of outer arm completion 1269:1307 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 2 102 theme glycosylation 376:388 arg1 machinery 390:398 the glycosylation machinery 372:398 the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg) 372:507 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 6 103 theme oligosaccharides 1538:1553 arg1 type 1530:1533 high-mannose type 1517:1533 high-mannose type of oligosaccharides 1517:1553 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 103 theme oligosaccharides 1538:1553 arg1 oligosaccharides 1538:1553 oligosaccharides 1538:1553 oligosaccharides 1538:1553 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 103 theme oligosaccharides 1538:1553 arg1 % 1436:1436 approximately 77% 1420:1436 approximately 77% of the glycans, with various levels of branching and outer arm completion, 1420:1511 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 6 103 theme oligosaccharides 1538:1553 arg1 glycans 1445:1451 the glycans 1441:1451 the glycans 1441:1451 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2059624 8 104 theme genes 2030:2034 arg1 activation 1959:1968 an activation 1956:1968 an activation of the appropriate glycosyl transferases and/or transferase genes 1956:2034 The time dependency of the assembly of complex-type oligosaccharides on r-HPg indicates that an activation of the appropriate glycosyl transferases and/or transferase genes can take place. 2059624 9 105 theme oligosaccharide 2246:2260 arg1 processing 2262:2271 complex-type oligosaccharide processing 2233:2271 complex-type oligosaccharide processing 2233:2271 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 0 106 theme oligosaccharide 18:32 arg1 processing 34:43 Asparagine-linked oligosaccharide processing 0:43 Asparagine-linked oligosaccharide processing in lepidopteran insect cells 0:72 Asparagine-linked oligosaccharide processing in lepidopteran insect cells. 2059624 7 107 theme proper 1844:1849 arg1 conditions 1851:1860 proper conditions 1844:1860 proper conditions 1844:1860 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 1 108 theme nature 102:107 arg1 dependence 84:93 Temporal dependence 75:93 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen 75:192 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 4 109 theme such 1022:1025 arg1 structures 1027:1036 such structures 1022:1036 such structures 1022:1036 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 4 110 theme postinfection 789:801 arg1 period 815:820 the earliest postinfection (p.i.) time period 776:820 the earliest postinfection (p.i.) time period studied 776:828 At the earliest postinfection (p.i.) time period studied, i.e., 0-20 h, virtually all (96%) of the oligosaccharides released with glycopeptidase F from N289 of the expressed r-HPg were of the high-mannose type and comprised nearly the full range of such structures, containing 3-9 mannose units. 2059624 5 111 theme complex 1247:1253 arg1 classes 1255:1261 the biantennary, triantennary, and tetraantennary complex classes 1197:1261 the biantennary, triantennary, and tetraantennary complex classes 1197:1261 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 7 112 theme lepidopteran 1675:1686 arg1 cells 1695:1699 lepidopteran insect cells 1675:1699 lepidopteran insect cells 1675:1699 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 0 113 theme insect 61:66 arg1 cells 68:72 lepidopteran insect cells 48:72 lepidopteran insect cells 48:72 Asparagine-linked oligosaccharide processing in lepidopteran insect cells. 2059624 9 114 theme complex-type 2233:2244 arg1 processing 2262:2271 complex-type oligosaccharide processing 2233:2271 complex-type oligosaccharide processing 2233:2271 Thus, one consequence of the infective process with the recombinant baculovirus/HPg-cDNA construct is to alter the normal glycosylation characteristics of insect cells and to allow complex-type oligosaccharide processing to occur. 2059624 1 115 dep infected 225:232 arg1 vector 218:223 baculovirus vector 206:223 baculovirus vector 206:223 Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells. 2059624 2 116 theme human 483:487 arg1 r-HPg 502:506 recombinant human plasminogen (r-HPg) 471:507 recombinant human plasminogen (r-HPg) 471:507 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 7 117 theme complex 1773:1779 arg1 oligosaccharide 1781:1795 N-linked complex oligosaccharide 1764:1795 N-linked complex oligosaccharide 1764:1795 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 7 118 contain contain 1701:1707 arg1 cells 1695:1699 lepidopteran insect cells 1675:1699 lepidopteran insect cells 1675:1699 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 7 118 contain contain 1701:1707 arg2 genes 1733:1737 the glycosyltransferase genes 1709:1737 the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide 1709:1795 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 3 119 theme cells 714:718 arg1 infection 697:705 infection 697:705 infection of the cells with the recombinant baculovirus/HPg-cDNA construct 697:770 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 7 120 theme oligosaccharide 1781:1795 arg1 assembly 1752:1759 assembly 1752:1759 assembly of N-linked complex oligosaccharide 1752:1795 These studies demonstrate that lepidopteran insect cells contain the glycosyltransferase genes required for assembly of N-linked complex oligosaccharide and that these transferases are utilized under proper conditions. 2059624 5 121 theme arm 1294:1296 arg1 completion 1298:1307 outer arm completion 1288:1307 outer arm completion 1288:1307 At a time window of 60-96 h, p.i., essentially all of the oligosaccharides (92% of the total) assembled on N289 of rHPg were of the biantennary, triantennary, and tetraantennary complex classes, with varying extents of outer arm completion. 2059624 2 122 theme complex-type 428:439 arg1 oligosaccharides 441:456 N-linked complex-type oligosaccharides 419:456 N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg) 419:507 Previous studies from this laboratory have established that lepidopteran insect cells possess the glycosylation machinery needed to assemble N-linked complex-type oligosaccharides on Asn289 of recombinant human plasminogen (r-HPg). 2059624 3 123 theme baculovirus/HPg-cDNA 741:760 arg1 construct 762:770 the recombinant baculovirus/HPg-cDNA construct 725:770 the recombinant baculovirus/HPg-cDNA construct 725:770 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 3 124 theme of 585:586 arg1 r-HPg 595:599 N289-linked glycosylation of [R561E]r-HPg 559:599 N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells 559:655 In the present paper, we show that the nature of N289-linked glycosylation of [R561E]r-HPg expressed in Spodoptera frugiperda (IPLB-SF-21AE) cells is dependent upon the length of time of infection of the cells with the recombinant baculovirus/HPg-cDNA construct. 2059624 6 125 theme complex-type 1380:1391 arg1 oligosaccharides 1393:1408 complex-type oligosaccharides 1380:1408 complex-type oligosaccharides 1380:1408 At an intermediate time period window, of 20-60 h, p.i., a mixture of complex-type oligosaccharides, totaling approximately 77% of the glycans, with various levels of branching and outer arm completion, and high-mannose type of oligosaccharides, totaling approximately 23% of the glycans, was assembled on N289 of the r-HPg produced. 2386787 5 0 from carbohydrate 1405:1416 arg1 proteins 1421:1428 proteins 1421:1428 proteins produced in insect cells 1421:1453 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 7 1 theme oligosaccharide 1974:1988 arg1 events 2001:2006 oligosaccharide processing events 1974:2006 oligosaccharide processing events 1974:2006 From these observations, we conclude that amino acid sequences and/or protein conformational properties can control oligosaccharide processing events. 2386787 2 2 theme earlier 848:854 arg1 work 856:859 earlier work 848:859 earlier work published by this laboratory 848:888 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 1 3 theme Asn289-linked 164:176 arg1 structures 194:203 the Asn289-linked oligosaccharide structures 160:203 the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, 160:332 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 2 4 theme compositional 669:681 arg1 analysis 683:690 monosaccharide compositional analysis 654:690 monosaccharide compositional analysis 654:690 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 6 5 theme oligosaccharides 1701:1716 arg1 trimming 1676:1683 trimming 1676:1683 trimming 1676:1683 Our data indicate that both normal and alternate pathways exist in these cells for incorporation and trimming of high-mannose oligosaccharides and that mannosidases, as well as galactosyl-, hexosaminidasyl-, and sialyltransferases are present, and/or can be induced, in these cells. 2386787 6 5 theme oligosaccharides 1701:1716 arg1 incorporation 1658:1670 incorporation 1658:1670 incorporation 1658:1670 Our data indicate that both normal and alternate pathways exist in these cells for incorporation and trimming of high-mannose oligosaccharides and that mannosidases, as well as galactosyl-, hexosaminidasyl-, and sialyltransferases are present, and/or can be induced, in these cells. 2386787 2 6 theme elution 583:589 arg1 positions 591:599 elution positions 583:599 elution positions of standard oligosaccharide structures 583:638 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 7 7 theme conformational 1936:1949 arg1 properties 1951:1960 protein conformational properties 1928:1960 protein conformational properties 1928:1960 From these observations, we conclude that amino acid sequences and/or protein conformational properties can control oligosaccharide processing events. 2386787 5 8 from proteins 1421:1428 arg1 This 1354:1357 This 1354:1357 This 1354:1357 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 5 8 from proteins 1421:1428 arg1 identification 1379:1392 the first direct identification 1362:1392 the first direct identification of complex carbohydrate in proteins produced in insect cells 1362:1453 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 2 9 theme bisialo-biantennary 746:764 arg1 carbohydrate 779:790 only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate 741:834 carbohydrate 779:790 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 1 10 theme human 208:212 arg1 plasminogen 221:231 human plasma plasminogen 208:231 human plasma plasminogen 208:231 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 1 11 theme plasminogen 221:231 arg1 structures 194:203 the Asn289-linked oligosaccharide structures 160:203 the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, 160:332 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 2 12 theme oligosaccharide 613:627 arg1 structures 629:638 standard oligosaccharide structures 604:638 standard oligosaccharide structures 604:638 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 2 13 theme complex-type 766:777 arg1 carbohydrate 779:790 only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate 741:834 carbohydrate 779:790 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 2 14 contain contained 731:739 arg2 carbohydrate 823:834 only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate 741:834 carbohydrate 823:834 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 2 14 contain contained 731:739 arg2 carbohydrate 779:790 only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate 741:834 carbohydrate 779:790 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 2 14 contain contained 731:739 arg1 protein 723:729 the human plasma protein 706:729 the human plasma protein 706:729 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 5 15 from identification 1379:1392 arg1 proteins 1421:1428 proteins 1421:1428 proteins produced in insect cells 1421:1453 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 1 16 theme human 418:422 arg1 cDNA 436:439 the entire human plasminogen cDNA 407:439 the entire human plasminogen cDNA 407:439 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 3 17 theme human 958:962 arg1 plasminogen 964:974 the insect cell expressed recombinant human plasminogen 920:974 the insect cell expressed recombinant human plasminogen 920:974 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 3 18 gly glycosylation 895:907 arg1 plasminogen 964:974 the insect cell expressed recombinant human plasminogen 920:974 the insect cell expressed recombinant human plasminogen 920:974 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 4 19 theme human 1332:1336 arg1 protein 1345:1351 the human plasma protein 1328:1351 the human plasma protein 1328:1351 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 3 20 theme glycosylation 895:907 arg1 pattern 909:915 The glycosylation pattern 891:915 The glycosylation pattern of the insect cell expressed recombinant human plasminogen 891:974 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 3 21 theme expressed 936:944 arg1 plasminogen 964:974 the insect cell expressed recombinant human plasminogen 920:974 the insect cell expressed recombinant human plasminogen 920:974 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 2 22 theme complex 815:821 arg1 carbohydrate 823:834 only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate 741:834 carbohydrate 823:834 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 5 23 theme insect 1442:1447 arg1 cells 1449:1453 insect cells 1442:1453 insect cells 1442:1453 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 0 24 theme cDNA 66:69 arg1 expression 34:43 the expression 30:43 the expression of human plasminogen cDNA 30:69 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 2386787 5 25 theme complex 1397:1403 arg1 carbohydrate 1405:1416 complex carbohydrate 1397:1416 complex carbohydrate in proteins produced in insect cells 1397:1453 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 3 26 theme insect 924:929 arg1 plasminogen 964:974 the insect cell expressed recombinant human plasminogen 920:974 the insect cell expressed recombinant human plasminogen 920:974 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 0 27 theme lepidopteran 74:85 arg1 insect 87:92 lepidopteran insect 74:92 lepidopteran insect (Spodoptera frugiperda) cells 74:122 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 2386787 0 27 theme lepidopteran 74:85 arg1 frugiperda 106:115 Spodoptera frugiperda 95:115 Spodoptera frugiperda 95:115 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 2386787 1 28 theme cells 359:363 arg1 infection 340:348 infection 340:348 infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA 340:439 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 3 29 theme high-mannose 1034:1045 arg1 Man9GlcNAc2 1061:1071 identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide 1021:1115 Man9GlcNAc2 1061:1071 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 7 30 theme amino 1900:1904 arg1 sequences 1911:1919 amino acid sequences 1900:1919 amino acid sequences 1900:1919 From these observations, we conclude that amino acid sequences and/or protein conformational properties can control oligosaccharide processing events. 2386787 4 31 theme major 1165:1169 arg1 importance 1171:1180 major importance 1165:1180 major importance 1165:1180 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 1 32 contain containing 396:405 arg1 baculovirus 384:394 a recombinant baculovirus 370:394 a recombinant baculovirus containing the entire human plasminogen cDNA 370:439 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 1 32 contain containing 396:405 arg2 cDNA 436:439 the entire human plasminogen cDNA 407:439 the entire human plasminogen cDNA 407:439 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 0 33 theme Oligosaccharide 0:14 arg1 processing 16:25 Oligosaccharide processing 0:25 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 0:123 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 2386787 1 34 theme lepidopteran 283:294 arg1 insect 296:301 lepidopteran insect 283:301 lepidopteran insect (Spodoptera frugiperda) cells 283:331 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 1 34 theme lepidopteran 283:294 arg1 frugiperda 315:324 Spodoptera frugiperda 304:324 Spodoptera frugiperda 304:324 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 2 35 theme anion-exchange 448:461 arg1 chromatography 470:483 anion-exchange liquid chromatography mapping 448:491 anion-exchange liquid chromatography mapping 448:491 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 2 36 theme human 710:714 arg1 protein 723:729 the human plasma protein 706:729 the human plasma protein 706:729 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 2 37 theme oligosaccharide 500:514 arg1 units 516:520 the oligosaccharide units 496:520 the oligosaccharide units cleaved from the proteins by glycopeptidase F 496:566 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 7 38 theme acid 1906:1909 arg1 sequences 1911:1919 amino acid sequences 1900:1919 amino acid sequences 1900:1919 From these observations, we conclude that amino acid sequences and/or protein conformational properties can control oligosaccharide processing events. 2386787 0 39 theme human 48:52 arg1 cDNA 66:69 human plasminogen cDNA 48:69 human plasminogen cDNA 48:69 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 2386787 3 40 theme truncated 1078:1086 arg1 oligosaccharide 1101:1115 identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide 1021:1115 oligosaccharide 1101:1115 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 4 41 theme oligosaccharide 1208:1222 arg1 population 1224:1233 the oligosaccharide population 1204:1233 the oligosaccharide population 1204:1233 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 5 42 theme carbohydrate 1517:1528 arg1 oligosaccharide 1548:1562 high-mannose carbohydrate into complex-type oligosaccharide 1504:1562 high-mannose carbohydrate into complex-type oligosaccharide 1504:1562 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 1 43 theme recombinant 239:249 arg1 plasminogen 257:267 a recombinant human plasminogen 237:267 a recombinant human plasminogen 237:267 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 5 44 theme complex-type 1535:1546 arg1 oligosaccharide 1548:1562 high-mannose carbohydrate into complex-type oligosaccharide 1504:1562 high-mannose carbohydrate into complex-type oligosaccharide 1504:1562 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 1 45 theme plasminogen 257:267 arg1 structures 194:203 the Asn289-linked oligosaccharide structures 160:203 the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, 160:332 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 7 46 theme processing 1990:1999 arg1 events 2001:2006 oligosaccharide processing events 1974:2006 oligosaccharide processing events 1974:2006 From these observations, we conclude that amino acid sequences and/or protein conformational properties can control oligosaccharide processing events. 2386787 2 47 theme structures 629:638 arg1 positions 591:599 elution positions 583:599 elution positions of standard oligosaccharide structures 583:638 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 4 48 from identical 1292:1300 arg1 structure 1305:1313 structure 1305:1313 structure 1305:1313 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 1 49 theme oligosaccharide 178:192 arg1 structures 194:203 the Asn289-linked oligosaccharide structures 160:203 the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, 160:332 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 2 50 theme monosaccharide 654:667 arg1 analysis 683:690 monosaccharide compositional analysis 654:690 monosaccharide compositional analysis 654:690 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 7 51 theme protein 1928:1934 arg1 properties 1951:1960 protein conformational properties 1928:1960 protein conformational properties 1928:1960 From these observations, we conclude that amino acid sequences and/or protein conformational properties can control oligosaccharide processing events. 2386787 4 52 theme complex 1248:1254 arg1 carbohydrate 1256:1267 complex carbohydrate 1248:1267 complex carbohydrate (bisialo-biantennary) 1248:1289 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 4 52 theme complex 1248:1254 arg1 bisialo-biantennary 1270:1288 bisialo-biantennary 1270:1288 bisialo-biantennary 1270:1288 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 6 53 theme high-mannose 1688:1699 arg1 oligosaccharides 1701:1716 high-mannose oligosaccharides 1688:1716 high-mannose oligosaccharides 1688:1716 Our data indicate that both normal and alternate pathways exist in these cells for incorporation and trimming of high-mannose oligosaccharides and that mannosidases, as well as galactosyl-, hexosaminidasyl-, and sialyltransferases are present, and/or can be induced, in these cells. 2386787 1 54 theme plasma 214:219 arg1 plasminogen 221:231 human plasma plasminogen 208:231 human plasma plasminogen 208:231 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 1 55 theme entire 411:416 arg1 cDNA 436:439 the entire human plasminogen cDNA 407:439 the entire human plasminogen cDNA 407:439 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 2 56 theme standard 604:611 arg1 structures 629:638 standard oligosaccharide structures 604:638 standard oligosaccharide structures 604:638 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 4 57 theme plasma 1338:1343 arg1 protein 1345:1351 the human plasma protein 1328:1351 the human plasma protein 1328:1351 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 1 58 theme plasminogen 424:434 arg1 cDNA 436:439 the entire human plasminogen cDNA 407:439 the entire human plasminogen cDNA 407:439 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 3 59 theme plasminogen 964:974 arg1 pattern 909:915 The glycosylation pattern 891:915 The glycosylation pattern of the insect cell expressed recombinant human plasminogen 891:974 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 3 60 theme considerable 983:994 arg1 microheterogeneity 996:1013 considerable microheterogeneity 983:1013 considerable microheterogeneity 983:1013 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 3 61 dep Man9GlcNAc2 1061:1071 arg1 Man4GlcNAc2 1131:1141 Man4GlcNAc2 1131:1141 Man4GlcNAc2 1131:1141 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 3 61 dep Man9GlcNAc2 1061:1071 arg1 Man3GlcNAc2 1148:1158 Man3GlcNAc2 1148:1158 Man3GlcNAc2 1148:1158 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 3 61 dep Man9GlcNAc2 1061:1071 arg1 Man5GlcNAc2 1118:1128 Man5GlcNAc2 1118:1128 Man5GlcNAc2 1118:1128 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 3 62 theme recombinant 946:956 arg1 plasminogen 964:974 the insect cell expressed recombinant human plasminogen 920:974 the insect cell expressed recombinant human plasminogen 920:974 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 2 63 theme asialo-biantennary 796:813 arg1 carbohydrate 823:834 only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate 741:834 carbohydrate 823:834 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 0 64 theme insect 87:92 arg1 cells 118:122 lepidopteran insect (Spodoptera frugiperda) cells 74:122 lepidopteran insect (Spodoptera frugiperda) cells 74:122 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 2386787 2 65 theme units 516:520 arg1 chromatography 470:483 anion-exchange liquid chromatography mapping 448:491 anion-exchange liquid chromatography mapping 448:491 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 0 66 from processing 16:25 arg1 expression 34:43 the expression 30:43 the expression of human plasminogen cDNA 30:69 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 2386787 5 67 theme carbohydrate 1405:1416 arg1 This 1354:1357 This 1354:1357 This 1354:1357 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 5 67 theme carbohydrate 1405:1416 arg1 identification 1379:1392 the first direct identification 1362:1392 the first direct identification of complex carbohydrate in proteins produced in insect cells 1362:1453 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 3 68 theme cell 931:934 arg1 plasminogen 964:974 the insect cell expressed recombinant human plasminogen 920:974 the insect cell expressed recombinant human plasminogen 920:974 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 0 69 theme Spodoptera 95:104 arg1 insect 87:92 lepidopteran insect 74:92 lepidopteran insect (Spodoptera frugiperda) cells 74:122 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 2386787 0 69 theme Spodoptera 95:104 arg1 frugiperda 106:115 Spodoptera frugiperda 95:115 Spodoptera frugiperda 95:115 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 2386787 1 70 with infection 340:348 arg1 baculovirus 384:394 a recombinant baculovirus 370:394 a recombinant baculovirus containing the entire human plasminogen cDNA 370:439 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 2 71 theme glycopeptidase 551:564 arg1 F 566:566 glycopeptidase F 551:566 glycopeptidase F 551:566 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 3 72 theme carbohydrate 1047:1058 arg1 Man9GlcNAc2 1061:1071 identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide 1021:1115 Man9GlcNAc2 1061:1071 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 6 73 theme alternate 1614:1622 arg1 pathways 1624:1631 both normal and alternate pathways 1598:1631 both normal and alternate pathways 1598:1631 Our data indicate that both normal and alternate pathways exist in these cells for incorporation and trimming of high-mannose oligosaccharides and that mannosidases, as well as galactosyl-, hexosaminidasyl-, and sialyltransferases are present, and/or can be induced, in these cells. 2386787 1 74 theme recombinant 372:382 arg1 baculovirus 384:394 a recombinant baculovirus 370:394 a recombinant baculovirus containing the entire human plasminogen cDNA 370:439 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 3 75 theme identifiable 1021:1032 arg1 Man9GlcNAc2 1061:1071 identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide 1021:1115 Man9GlcNAc2 1061:1071 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 2 76 theme liquid 463:468 arg1 chromatography 470:483 anion-exchange liquid chromatography mapping 448:491 anion-exchange liquid chromatography mapping 448:491 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 1 77 link Asn289-linked 164:176 arg1 structures 194:203 the Asn289-linked oligosaccharide structures 160:203 the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, 160:332 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 2 78 theme plasma 716:721 arg1 protein 723:729 the human plasma protein 706:729 the human plasma protein 706:729 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 6 79 theme normal 1603:1608 arg1 pathways 1624:1631 both normal and alternate pathways 1598:1631 both normal and alternate pathways 1598:1631 Our data indicate that both normal and alternate pathways exist in these cells for incorporation and trimming of high-mannose oligosaccharides and that mannosidases, as well as galactosyl-, hexosaminidasyl-, and sialyltransferases are present, and/or can be induced, in these cells. 2386787 1 80 theme insect 296:301 arg1 cells 327:331 lepidopteran insect (Spodoptera frugiperda) cells 283:331 lepidopteran insect (Spodoptera frugiperda) cells 283:331 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 4 81 with identical 1292:1300 arg1 that 1320:1323 that 1320:1323 that 1320:1323 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 1 82 theme Spodoptera 304:313 arg1 insect 296:301 lepidopteran insect 283:301 lepidopteran insect (Spodoptera frugiperda) cells 283:331 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 1 82 theme Spodoptera 304:313 arg1 frugiperda 315:324 Spodoptera frugiperda 304:324 Spodoptera frugiperda 304:324 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2386787 5 83 theme direct 1372:1377 arg1 This 1354:1357 This 1354:1357 This 1354:1357 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 5 83 theme direct 1372:1377 arg1 identification 1379:1392 the first direct identification 1362:1392 the first direct identification of complex carbohydrate in proteins produced in insect cells 1362:1453 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 5 84 theme oligosaccharide 1548:1562 arg1 processing 1490:1499 processing 1490:1499 processing 1490:1499 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 5 84 theme oligosaccharide 1548:1562 arg1 trimming 1477:1484 trimming 1477:1484 trimming 1477:1484 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 0 85 theme plasminogen 54:64 arg1 cDNA 66:69 human plasminogen cDNA 48:69 human plasminogen cDNA 48:69 Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. 2386787 2 86 theme mapping 485:491 arg1 chromatography 470:483 anion-exchange liquid chromatography mapping 448:491 anion-exchange liquid chromatography mapping 448:491 Using anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the proteins by glycopeptidase F, compared with elution positions of standard oligosaccharide structures, coupled with monosaccharide compositional analysis, we find that the human plasma protein contained only bisialo-biantennary complex-type carbohydrate and asialo-biantennary complex carbohydrate, confirming earlier work published by this laboratory. 2386787 3 87 theme high-mannose 1088:1099 arg1 oligosaccharide 1101:1115 identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide 1021:1115 oligosaccharide 1101:1115 The glycosylation pattern of the insect cell expressed recombinant human plasminogen showed considerable microheterogeneity, with identifiable high-mannose carbohydrate (Man9GlcNAc2) and truncated high-mannose oligosaccharide (Man5GlcNAc2, Man4GlcNAc2, and Man3GlcNAc2). 2386787 5 88 theme high-mannose 1504:1515 arg1 oligosaccharide 1548:1562 high-mannose carbohydrate into complex-type oligosaccharide 1504:1562 high-mannose carbohydrate into complex-type oligosaccharide 1504:1562 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 5 89 theme first 1366:1370 arg1 This 1354:1357 This 1354:1357 This 1354:1357 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 5 89 theme first 1366:1370 arg1 identification 1379:1392 the first direct identification 1362:1392 the first direct identification of complex carbohydrate in proteins produced in insect cells 1362:1453 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 4 90 from structure 1305:1313 arg1 identical 1292:1300 identical 1292:1300 identical 1292:1300 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 4 91 theme population 1224:1233 arg1 % 1199:1199 approximately 40% 1183:1199 approximately 40% of the oligosaccharide population 1183:1233 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 4 91 theme population 1224:1233 arg1 population 1224:1233 the oligosaccharide population 1204:1233 the oligosaccharide population 1204:1233 Of major importance, approximately 40% of the oligosaccharide population consisted of complex carbohydrate (bisialo-biantennary), identical in structure with that of the human plasma protein. 2386787 5 92 theme into 1530:1533 arg1 oligosaccharide 1548:1562 high-mannose carbohydrate into complex-type oligosaccharide 1504:1562 high-mannose carbohydrate into complex-type oligosaccharide 1504:1562 This is the first direct identification of complex carbohydrate in proteins produced in insect cells and demonstrates that trimming and processing of high-mannose carbohydrate into complex-type oligosaccharide can occur. 2386787 1 93 theme human 251:255 arg1 plasminogen 257:267 a recombinant human plasminogen 237:267 a recombinant human plasminogen 237:267 A comparison has been made between the Asn289-linked oligosaccharide structures of human plasma plasminogen and a recombinant human plasminogen, expressed in lepidopteran insect (Spodoptera frugiperda) cells, after infection of these cells with a recombinant baculovirus containing the entire human plasminogen cDNA. 2065054 1 0 theme baculovirus 617:627 arg1 vector 629:634 a baculovirus vector 615:634 a baculovirus vector 615:634 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 3 1 theme N-linked 1230:1237 arg1 oligosaccharides 1239:1254 the total N-linked oligosaccharides 1220:1254 the total N-linked oligosaccharides 1220:1254 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 0 2 link asparagine-289-linked 18:38 arg1 oligosaccharides 40:55 the asparagine-289-linked oligosaccharides 14:55 the asparagine-289-linked oligosaccharides 14:55 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 2 3 theme Mamestra 900:907 arg1 cells 932:936 Mamestra brassicae (IZD-MBO503) cells 900:936 Mamestra brassicae (IZD-MBO503) cells for 48 h 900:945 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 4 theme complex 735:741 arg1 oligosaccharide 743:757 complex oligosaccharide 735:757 complex oligosaccharide 735:757 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 0 5 theme Mamestra 115:122 arg1 IZD-MBO503 145:154 IZD-MBO503 145:154 IZD-MBO503 145:154 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 0 5 theme Mamestra 115:122 arg1 line 139:142 Mamestra brassicae cell line 115:142 a Mamestra brassicae cell line (IZD-MBO503) 113:155 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 4 6 theme high-mannose 1543:1554 arg1 type 1556:1559 the high-mannose type 1539:1559 the high-mannose type 1539:1559 The remainder of the oligosaccharides were of the high-mannose type, with (mannose)9(N-acetylglucosamine)2 (22%), (mannose)5(N-acetylglucosamine)2 (13%), and (mannose)3(N-acetylglucosamine)2 (2%) representing the major oligosaccharides observed. 2065054 1 7 from report 166:171 arg1 fortified 182:190 fortified 182:190 fortified 182:190 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 3 8 theme oligosaccharides 1239:1254 arg1 oligosaccharides 1239:1254 the total N-linked oligosaccharides 1220:1254 the total N-linked oligosaccharides 1220:1254 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 8 theme oligosaccharides 1239:1254 arg1 % 1215:1215 approximately 63% 1199:1215 approximately 63% of the total N-linked oligosaccharides 1199:1254 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 2 9 theme chemical 788:795 arg1 nature 797:802 the chemical nature 784:802 the chemical nature of the types of oligosaccharides that such insect cells were able to assemble 784:880 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 3 10 with type 1276:1279 arg1 % 1374:1374 25% 1372:1374 25% 1372:1374 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 10 with type 1276:1279 arg1 % 1310:1310 28% 1308:1310 28% 1308:1310 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 10 with type 1276:1279 arg1 % 1415:1415 3% 1414:1415 3% 1414:1415 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 10 with type 1276:1279 arg1 asialo-biantennary 1314:1331 asialo-biantennary 1314:1331 asialo-biantennary 1314:1331 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 10 with type 1276:1279 arg1 oligosaccharides 1418:1433 fucosylated asialo-biantennary (3%) oligosaccharides 1382:1433 fucosylated asialo-biantennary (3%) oligosaccharides 1382:1433 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 10 with type 1276:1279 arg1 bisialo-biantennary 1351:1369 bisialo-biantennary 1351:1369 bisialo-biantennary 1351:1369 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 10 with type 1276:1279 arg1 bisialo-biantennary 1287:1305 bisialo-biantennary 1287:1305 bisialo-biantennary 1287:1305 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 10 with type 1276:1279 arg1 % 1335:1335 7% 1334:1335 7% 1334:1335 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 11 theme total 1224:1228 arg1 oligosaccharides 1239:1254 the total N-linked oligosaccharides 1220:1254 the total N-linked oligosaccharides 1220:1254 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 1 12 theme lepidopteran 367:378 arg1 insect 380:385 lepidopteran insect 367:385 lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) 367:430 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 12 theme lepidopteran 367:378 arg1 frugiperda 399:408 Spodoptera frugiperda 388:408 Spodoptera frugiperda 388:408 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 2 13 theme [R561E 997:1002 arg1 plasminogen 1010:1020 the [R561E]human plasminogen 993:1020 the [R561E]human plasminogen (HPg) cDNA 993:1031 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 13 theme [R561E 997:1002 arg1 HPg 1023:1025 HPg 1023:1025 HPg 1023:1025 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 1 14 theme N-linked 459:466 arg1 oligosaccharide 476:490 N-linked complex oligosaccharide 459:490 N-linked complex oligosaccharide 459:490 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 0 15 theme cell 134:137 arg1 IZD-MBO503 145:154 IZD-MBO503 145:154 IZD-MBO503 145:154 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 0 15 theme cell 134:137 arg1 line 139:142 Mamestra brassicae cell line 115:142 a Mamestra brassicae cell line (IZD-MBO503) 113:155 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 1 16 dep J 280:280 arg1 Biochemistry 290:301 Biochemistry 290:301 Biochemistry 290:301 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 17 theme insect 380:385 arg1 IPLB-SF-21AE 418:429 IPLB-SF-21AE 418:429 IPLB-SF-21AE 418:429 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 17 theme insect 380:385 arg1 cells 411:415 lepidopteran insect (Spodoptera frugiperda) cells 367:415 lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) 367:430 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 18 theme complex 468:474 arg1 oligosaccharide 476:490 N-linked complex oligosaccharide 459:490 N-linked complex oligosaccharide 459:490 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 2 19 theme GF 1087:1088 arg1 oligosaccharides 1109:1124 the glycopeptidase F (GF) released N-linked oligosaccharides 1065:1124 the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells 1065:1182 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 0 20 theme brassicae 124:132 arg1 IZD-MBO503 145:154 IZD-MBO503 145:154 IZD-MBO503 145:154 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 0 20 theme brassicae 124:132 arg1 line 139:142 Mamestra brassicae cell line 115:142 a Mamestra brassicae cell line (IZD-MBO503) 113:155 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 1 21 link N-linked 459:466 arg1 oligosaccharide 476:490 N-linked complex oligosaccharide 459:490 N-linked complex oligosaccharide 459:490 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 4 22 theme mannose 1608:1614 arg1 % 1643:1643 13% 1641:1643 13% 1641:1643 The remainder of the oligosaccharides were of the high-mannose type, with (mannose)9(N-acetylglucosamine)2 (22%), (mannose)5(N-acetylglucosamine)2 (13%), and (mannose)3(N-acetylglucosamine)2 (2%) representing the major oligosaccharides observed. 2065054 4 22 theme mannose 1608:1614 arg1 N-acetylglucosamine 1618:1636 (mannose)5(N-acetylglucosamine)2 1607:1638 (mannose)5(N-acetylglucosamine)2 (13%) 1607:1644 The remainder of the oligosaccharides were of the high-mannose type, with (mannose)9(N-acetylglucosamine)2 (22%), (mannose)5(N-acetylglucosamine)2 (13%), and (mannose)3(N-acetylglucosamine)2 (2%) representing the major oligosaccharides observed. 2065054 2 23 dep order 640:644 arg1 identify 775:782 identify 775:782 to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble 772:880 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 23 dep order 640:644 arg1 investigate 649:659 investigate 649:659 to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed 646:765 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 24 theme such 842:845 arg1 cells 854:858 such insect cells 842:858 such insect cells 842:858 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 4 25 theme oligosaccharides 1514:1529 arg1 remainder 1497:1505 The remainder 1493:1505 The remainder of the oligosaccharides 1493:1529 The remainder of the oligosaccharides were of the high-mannose type, with (mannose)9(N-acetylglucosamine)2 (22%), (mannose)5(N-acetylglucosamine)2 (13%), and (mannose)3(N-acetylglucosamine)2 (2%) representing the major oligosaccharides observed. 2065054 1 26 theme Spodoptera 388:397 arg1 insect 380:385 lepidopteran insect 367:385 lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) 367:430 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 26 theme Spodoptera 388:397 arg1 frugiperda 399:408 Spodoptera frugiperda 388:408 Spodoptera frugiperda 388:408 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 2 27 theme F 1084:1084 arg1 oligosaccharides 1109:1124 the glycopeptidase F (GF) released N-linked oligosaccharides 1065:1124 the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells 1065:1182 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 28 contain containing 982:991 arg1 r 967:967 r 967:967 r 967:967 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 28 contain containing 982:991 arg2 cDNA 1028:1031 the [R561E]human plasminogen (HPg) cDNA 993:1031 the [R561E]human plasminogen (HPg) cDNA 993:1031 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 28 contain containing 982:991 arg1 baculovirus 970:980 a recombinant (r) baculovirus 952:980 a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA 952:1031 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 29 link N-linked 1100:1107 arg1 oligosaccharides 1109:1124 the glycopeptidase F (GF) released N-linked oligosaccharides 1065:1124 the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells 1065:1182 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 30 theme glycopeptidase 1069:1082 arg1 oligosaccharides 1109:1124 the glycopeptidase F (GF) released N-linked oligosaccharides 1065:1124 the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells 1065:1182 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 0 31 theme asparagine-289-linked 18:38 arg1 oligosaccharides 40:55 the asparagine-289-linked oligosaccharides 14:55 the asparagine-289-linked oligosaccharides 14:55 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 2 32 theme plasminogen 1010:1020 arg1 cDNA 1028:1031 the [R561E]human plasminogen (HPg) cDNA 993:1031 the [R561E]human plasminogen (HPg) cDNA 993:1031 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 1 33 theme human 497:501 arg1 plasminogen 512:522 plasminogen 512:522 plasminogen 512:522 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 33 theme human 497:501 arg1 protein 503:509 a human protein 495:509 a human protein (plasminogen) 495:523 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 2 34 theme oligosaccharides 1109:1124 arg1 nature 1055:1060 the nature 1051:1060 the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells 1051:1182 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 35 theme types 811:815 arg1 nature 797:802 the chemical nature 784:802 the chemical nature of the types of oligosaccharides that such insect cells were able to assemble 784:880 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 4 36 theme mannose 1568:1574 arg1 % 1603:1603 22% 1601:1603 22% 1601:1603 The remainder of the oligosaccharides were of the high-mannose type, with (mannose)9(N-acetylglucosamine)2 (22%), (mannose)5(N-acetylglucosamine)2 (13%), and (mannose)3(N-acetylglucosamine)2 (2%) representing the major oligosaccharides observed. 2065054 4 36 theme mannose 1568:1574 arg1 N-acetylglucosamine 1578:1596 (mannose)9(N-acetylglucosamine)2 1567:1598 (mannose)9(N-acetylglucosamine)2 (22%) 1567:1604 The remainder of the oligosaccharides were of the high-mannose type, with (mannose)9(N-acetylglucosamine)2 (22%), (mannose)5(N-acetylglucosamine)2 (13%), and (mannose)3(N-acetylglucosamine)2 (2%) representing the major oligosaccharides observed. 2065054 2 37 theme IZD-MBO503 920:929 arg1 cells 932:936 Mamestra brassicae (IZD-MBO503) cells 900:936 Mamestra brassicae (IZD-MBO503) cells for 48 h 900:945 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 38 theme human 1004:1008 arg1 plasminogen 1010:1020 the [R561E]human plasminogen 993:1020 the [R561E]human plasminogen (HPg) cDNA 993:1031 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 38 theme human 1004:1008 arg1 HPg 1023:1025 HPg 1023:1025 HPg 1023:1025 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 1 39 theme protein 503:509 arg1 cDNA 530:533 the cDNA 526:533 the cDNA 526:533 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 2 40 theme N-linked 1100:1107 arg1 oligosaccharides 1109:1124 the glycopeptidase F (GF) released N-linked oligosaccharides 1065:1124 the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells 1065:1182 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 41 contain contained 1126:1134 arg1 Asn289 1139:1144 Asn289 1139:1144 Asn289 of the r-HPg expressed by these cells 1139:1182 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 41 contain contained 1126:1134 arg2 oligosaccharides 1109:1124 the glycopeptidase F (GF) released N-linked oligosaccharides 1065:1124 the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells 1065:1182 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 3 42 theme fucosylated 1382:1392 arg1 % 1415:1415 3% 1414:1415 3% 1414:1415 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 42 theme fucosylated 1382:1392 arg1 oligosaccharides 1418:1433 fucosylated asialo-biantennary (3%) oligosaccharides 1382:1433 fucosylated asialo-biantennary (3%) oligosaccharides 1382:1433 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 2 43 theme recombinant 954:964 arg1 r 967:967 r 967:967 r 967:967 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 43 theme recombinant 954:964 arg1 baculovirus 970:980 a recombinant (r) baculovirus 952:980 a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA 952:1031 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 44 theme released 1091:1098 arg1 oligosaccharides 1109:1124 the glycopeptidase F (GF) released N-linked oligosaccharides 1065:1124 the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells 1065:1182 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 0 45 theme oligosaccharides 40:55 arg1 Structures 0:9 Structures 0:9 Structures of the asparagine-289-linked oligosaccharides 0:55 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 3 46 theme carbohydrate 1471:1482 arg1 species 1484:1490 the major complex-type carbohydrate species 1448:1490 the major complex-type carbohydrate species 1448:1490 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 47 theme asialo-biantennary 1394:1411 arg1 % 1415:1415 3% 1414:1415 3% 1414:1415 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 47 theme asialo-biantennary 1394:1411 arg1 oligosaccharides 1418:1433 fucosylated asialo-biantennary (3%) oligosaccharides 1382:1433 fucosylated asialo-biantennary (3%) oligosaccharides 1382:1433 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 2 48 theme brassicae 909:917 arg1 cells 932:936 Mamestra brassicae (IZD-MBO503) cells 900:936 Mamestra brassicae (IZD-MBO503) cells for 48 h 900:945 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 1 49 theme previous 207:214 arg1 [Davidson 230:238 a previous investigation [Davidson 205:238 a previous investigation [Davidson 205:238 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 49 theme previous 207:214 arg1 J 280:280 J 280:280 J 280:280 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 50 theme recombinant 583:593 arg1 technology 599:608 recombinant DNA technology 583:608 recombinant DNA technology with a baculovirus vector 583:634 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 2 51 theme insect 847:852 arg1 cells 854:858 such insect cells 842:858 such insect cells 842:858 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 0 52 theme human 82:86 arg1 plasminogen 88:98 recombinant human plasminogen 70:98 recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503) 70:155 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 4 53 theme mannose 1652:1658 arg1 % 1686:1686 2% 1685:1686 2% 1685:1686 The remainder of the oligosaccharides were of the high-mannose type, with (mannose)9(N-acetylglucosamine)2 (22%), (mannose)5(N-acetylglucosamine)2 (13%), and (mannose)3(N-acetylglucosamine)2 (2%) representing the major oligosaccharides observed. 2065054 4 53 theme mannose 1652:1658 arg1 N-acetylglucosamine 1662:1680 (mannose)3(N-acetylglucosamine)2 1651:1682 (mannose)3(N-acetylglucosamine)2 (2%) 1651:1687 The remainder of the oligosaccharides were of the high-mannose type, with (mannose)9(N-acetylglucosamine)2 (22%), (mannose)5(N-acetylglucosamine)2 (13%), and (mannose)3(N-acetylglucosamine)2 (2%) representing the major oligosaccharides observed. 2065054 3 54 gly fucosylated 1382:1392 arg1 % 1415:1415 3% 1414:1415 3% 1414:1415 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 54 gly fucosylated 1382:1392 arg1 oligosaccharides 1418:1433 fucosylated asialo-biantennary (3%) oligosaccharides 1382:1433 fucosylated asialo-biantennary (3%) oligosaccharides 1382:1433 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 1 55 theme DNA 595:597 arg1 technology 599:608 recombinant DNA technology 583:608 recombinant DNA technology with a baculovirus vector 583:634 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 56 dep Biochemistry 290:301 arg1 demonstrated 330:341 demonstrated 330:341 demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector 330:634 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 3 57 theme complex 1268:1274 arg1 type 1276:1279 the complex type 1264:1279 the complex type 1264:1279 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 2 58 theme r-HPg 1153:1157 arg1 Asn289 1139:1144 Asn289 1139:1144 Asn289 of the r-HPg expressed by these cells 1139:1182 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 59 theme general 676:682 arg1 capability 684:693 a more general capability 669:693 a more general capability of lepidopteran insect cells to produce complex oligosaccharide 669:757 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 2 60 theme cells 718:722 arg1 capability 684:693 a more general capability 669:693 a more general capability of lepidopteran insect cells to produce complex oligosaccharide 669:757 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 1 61 theme investigation 216:228 arg1 [Davidson 230:238 a previous investigation [Davidson 205:238 a previous investigation [Davidson 205:238 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 61 theme investigation 216:228 arg1 J 280:280 J 280:280 J 280:280 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 2 62 theme insect 711:716 arg1 cells 718:722 lepidopteran insect cells 698:722 lepidopteran insect cells 698:722 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 3 63 theme complex-type 1458:1469 arg1 species 1484:1490 the major complex-type carbohydrate species 1448:1490 the major complex-type carbohydrate species 1448:1490 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 3 64 link N-linked 1230:1237 arg1 oligosaccharides 1239:1254 the total N-linked oligosaccharides 1220:1254 the total N-linked oligosaccharides 1220:1254 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 1 65 theme first 351:355 arg1 time 357:360 the first time 347:360 the first time 347:360 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 66 with technology 599:608 arg1 vector 629:634 a baculovirus vector 615:634 a baculovirus vector 615:634 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 1 67 from fortified 182:190 arg1 report 166:171 this report 161:171 this report 161:171 In this report, we have fortified and extended a previous investigation [Davidson, D. J., Fraser, M. J., & Castellino, F. J. (1990) Biochemistry 29, 5584-5590] in which we demonstrated for the first time that lepidopteran insect (Spodoptera frugiperda) cells (IPLB-SF-21AE) were capable of assembling N-linked complex oligosaccharide on a human protein (plasminogen), the cDNA of which had been inserted into these cells via recombinant DNA technology with a baculovirus vector. 2065054 2 68 theme lepidopteran 698:709 arg1 cells 718:722 lepidopteran insect cells 698:722 lepidopteran insect cells 698:722 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 2065054 0 69 theme recombinant 70:80 arg1 plasminogen 88:98 recombinant human plasminogen 70:98 recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503) 70:155 Structures of the asparagine-289-linked oligosaccharides assembled on recombinant human plasminogen expressed in a Mamestra brassicae cell line (IZD-MBO503). 2065054 4 70 theme major 1706:1710 arg1 oligosaccharides 1712:1727 the major oligosaccharides 1702:1727 the major oligosaccharides observed 1702:1736 The remainder of the oligosaccharides were of the high-mannose type, with (mannose)9(N-acetylglucosamine)2 (22%), (mannose)5(N-acetylglucosamine)2 (13%), and (mannose)3(N-acetylglucosamine)2 (2%) representing the major oligosaccharides observed. 2065054 3 71 theme major 1452:1456 arg1 species 1484:1490 the major complex-type carbohydrate species 1448:1490 the major complex-type carbohydrate species 1448:1490 We found that approximately 63% of the total N-linked oligosaccharides were of the complex type, with bisialo-biantennary (28%), asialo-biantennary (7%), fucosylated bisialo-biantennary (25%), and fucosylated asialo-biantennary (3%) oligosaccharides representing the major complex-type carbohydrate species. 2065054 2 72 theme oligosaccharides 820:835 arg1 types 811:815 the types 807:815 the types of oligosaccharides that such insect cells were able to assemble 807:880 In order to investigate whether a more general capability of lepidopteran insect cells to produce complex oligosaccharide existed, and to identify the chemical nature of the types of oligosaccharides that such insect cells were able to assemble, we have infected Mamestra brassicae (IZD-MBO503) cells for 48 h with a recombinant (r) baculovirus containing the [R561E]human plasminogen (HPg) cDNA and characterized the nature of the glycopeptidase F (GF) released N-linked oligosaccharides contained on Asn289 of the r-HPg expressed by these cells. 10920251 0 0 theme IX 76:77 arg1 chains 38:43 N-linked sugar chains 23:43 N-linked sugar chains of human blood clotting factor IX 23:77 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 10920251 5 1 link N-linked 486:493 arg1 chains 501:506 the N-linked sugar chains 482:506 the N-linked sugar chains of human factor IX 482:525 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 1 2 theme IX 139:140 arg1 N-glycans 98:106 N-glycans 98:106 N-glycans of human blood clotting factor IX 98:140 The structures of N-glycans of human blood clotting factor IX were studied. 10920251 6 3 theme sialylated 639:648 arg1 chains 656:661 These highly sialylated sugar chains 626:661 These highly sialylated sugar chains 626:661 These highly sialylated sugar chains are located on the activation peptide of the protein. 10920251 0 4 theme factor 69:74 arg1 IX 76:77 human blood clotting factor IX 48:77 human blood clotting factor IX 48:77 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 10920251 0 5 link N-linked 23:30 arg1 chains 38:43 N-linked sugar chains 23:43 N-linked sugar chains of human blood clotting factor IX 23:77 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 10920251 5 6 theme fucose 609:614 arg1 residues 616:623 fucose residues 609:623 fucose residues 609:623 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 4 7 theme sugar 407:411 arg1 mapping 413:419 two-dimensional sugar mapping 391:419 two-dimensional sugar mapping combined with glycosidase digestion 391:455 Each PA-sugar chain was analyzed by two-dimensional sugar mapping combined with glycosidase digestion. 10920251 5 8 theme sugar 495:499 arg1 chains 501:506 the N-linked sugar chains 482:506 the N-linked sugar chains of human factor IX 482:525 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 4 9 theme two-dimensional 391:405 arg1 mapping 413:419 two-dimensional sugar mapping 391:419 two-dimensional sugar mapping combined with glycosidase digestion 391:455 Each PA-sugar chain was analyzed by two-dimensional sugar mapping combined with glycosidase digestion. 10920251 5 10 theme chains 501:506 arg1 structures 468:477 The major structures 458:477 The major structures of the N-linked sugar chains of human factor IX 458:525 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 5 10 theme chains 501:506 arg1 sialotetraantennary 544:562 sialotetraantennary 544:562 sialotetraantennary 544:562 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 4 11 theme PA-sugar 360:367 arg1 chain 369:373 Each PA-sugar chain 355:373 Each PA-sugar chain 355:373 Each PA-sugar chain was analyzed by two-dimensional sugar mapping combined with glycosidase digestion. 10920251 6 12 theme protein 708:714 arg1 peptide 693:699 the activation peptide 678:699 the activation peptide of the protein 678:714 These highly sialylated sugar chains are located on the activation peptide of the protein. 10920251 5 13 theme human 511:515 arg1 IX 524:525 human factor IX 511:525 human factor IX 511:525 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 0 14 theme Structural 0:9 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 0:78 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 10920251 0 15 theme N-linked 23:30 arg1 chains 38:43 N-linked sugar chains 23:43 N-linked sugar chains of human blood clotting factor IX 23:77 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 10920251 3 16 theme pyridylamino 286:297 arg1 chains 311:316 The pyridylamino (PA-) sugar chains 282:316 The pyridylamino (PA-) sugar chains thus obtained 282:330 The pyridylamino (PA-) sugar chains thus obtained were purified by HPLC. 10920251 6 17 theme activation 682:691 arg1 peptide 693:699 the activation peptide 678:699 the activation peptide of the protein 678:714 These highly sialylated sugar chains are located on the activation peptide of the protein. 10920251 0 18 theme chains 38:43 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 0:78 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 10920251 2 19 theme sugar 233:237 arg1 residues 239:246 the reducing-end sugar residues 216:246 the reducing-end sugar residues 216:246 N-Glycans liberated by hydrazinolysis were N-acetylated and the reducing-end sugar residues were tagged with 2-aminopyridine. 10920251 5 20 theme N-linked 486:493 arg1 chains 501:506 the N-linked sugar chains 482:506 the N-linked sugar chains of human factor IX 482:525 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 0 21 theme sugar 32:36 arg1 chains 38:43 N-linked sugar chains 23:43 N-linked sugar chains of human blood clotting factor IX 23:77 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 10920251 2 22 theme reducing-end 220:231 arg1 residues 239:246 the reducing-end sugar residues 216:246 the reducing-end sugar residues 216:246 N-Glycans liberated by hydrazinolysis were N-acetylated and the reducing-end sugar residues were tagged with 2-aminopyridine. 10920251 0 23 theme human 48:52 arg1 IX 76:77 human blood clotting factor IX 48:77 human blood clotting factor IX 48:77 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 10920251 6 24 located located 667:673 arg1 peptide 693:699 the activation peptide 678:699 the activation peptide of the protein 678:714 These highly sialylated sugar chains are located on the activation peptide of the protein. 10920251 6 24 located located 667:673 arg2 chains 656:661 These highly sialylated sugar chains 626:661 These highly sialylated sugar chains 626:661 These highly sialylated sugar chains are located on the activation peptide of the protein. 10920251 1 25 theme N-glycans 98:106 arg1 structures 84:93 The structures 80:93 The structures of N-glycans of human blood clotting factor IX 80:140 The structures of N-glycans of human blood clotting factor IX were studied. 10920251 3 26 theme sugar 305:309 arg1 chains 311:316 The pyridylamino (PA-) sugar chains 282:316 The pyridylamino (PA-) sugar chains thus obtained 282:330 The pyridylamino (PA-) sugar chains thus obtained were purified by HPLC. 10920251 5 27 theme sialotriantennary 568:584 arg1 chains 586:591 sialotriantennary chains 568:591 sialotriantennary chains with or without fucose residues 568:623 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 1 28 theme human 111:115 arg1 IX 139:140 human blood clotting factor IX 111:140 human blood clotting factor IX 111:140 The structures of N-glycans of human blood clotting factor IX were studied. 10920251 3 29 theme PA- 300:302 arg1 chains 311:316 The pyridylamino (PA-) sugar chains 282:316 The pyridylamino (PA-) sugar chains thus obtained 282:330 The pyridylamino (PA-) sugar chains thus obtained were purified by HPLC. 10920251 4 30 theme glycosidase 435:445 arg1 digestion 447:455 glycosidase digestion 435:455 glycosidase digestion 435:455 Each PA-sugar chain was analyzed by two-dimensional sugar mapping combined with glycosidase digestion. 10920251 5 31 theme factor 517:522 arg1 IX 524:525 human factor IX 511:525 human factor IX 511:525 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 1 32 theme blood 117:121 arg1 IX 139:140 human blood clotting factor IX 111:140 human blood clotting factor IX 111:140 The structures of N-glycans of human blood clotting factor IX were studied. 10920251 0 33 theme clotting 60:67 arg1 IX 76:77 human blood clotting factor IX 48:77 human blood clotting factor IX 48:77 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 10920251 5 34 theme IX 524:525 arg1 chains 501:506 the N-linked sugar chains 482:506 the N-linked sugar chains of human factor IX 482:525 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 1 35 theme clotting 123:130 arg1 IX 139:140 human blood clotting factor IX 111:140 human blood clotting factor IX 111:140 The structures of N-glycans of human blood clotting factor IX were studied. 10920251 5 36 theme major 462:466 arg1 structures 468:477 The major structures 458:477 The major structures of the N-linked sugar chains of human factor IX 458:525 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 5 36 theme major 462:466 arg1 sialotetraantennary 544:562 sialotetraantennary 544:562 sialotetraantennary 544:562 The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. 10920251 0 37 theme blood 54:58 arg1 IX 76:77 human blood clotting factor IX 48:77 human blood clotting factor IX 48:77 Structural analysis of N-linked sugar chains of human blood clotting factor IX. 10920251 6 38 gly sialylated 639:648 arg1 chains 656:661 These highly sialylated sugar chains 626:661 These highly sialylated sugar chains 626:661 These highly sialylated sugar chains are located on the activation peptide of the protein. 10920251 1 39 theme factor 132:137 arg1 IX 139:140 human blood clotting factor IX 111:140 human blood clotting factor IX 111:140 The structures of N-glycans of human blood clotting factor IX were studied. 10920251 6 40 theme sugar 650:654 arg1 chains 656:661 These highly sialylated sugar chains 626:661 These highly sialylated sugar chains 626:661 These highly sialylated sugar chains are located on the activation peptide of the protein. 10814696 4 0 theme MALDI 1072:1076 arg1 spectrometry 1058:1069 matrix-assisted laser desorption/ionization mass spectrometry 1009:1069 matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) 1009:1080 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 4 0 theme MALDI 1072:1076 arg1 MS 1078:1079 MALDI MS 1072:1079 MALDI MS 1072:1079 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 1 1 theme tumor 410:414 arg1 tissues 416:422 tumor tissues 410:422 tumor tissues 410:422 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 5 2 theme resulting 1229:1237 arg1 masses 1239:1244 the resulting masses 1225:1244 the resulting masses 1225:1244 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 2 3 theme A 594:594 arg1 glycosylation 563:575 the glycosylation 559:575 the glycosylation of arylsulfatase A in cancer 559:604 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 7 4 theme arylsulfatase 1460:1472 arg1 A 1474:1474 human placental arylsulfatase A 1444:1474 human placental arylsulfatase A 1444:1474 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 3 5 theme present 700:706 arg1 study 708:712 the present study 696:712 the present study 696:712 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 0 6 theme glycans 185:191 arg1 structure 168:176 the structure 164:176 the structure of its glycans 164:191 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 7 7 theme oligosaccharides 1509:1524 arg1 half 1543:1546 almost half 1536:1546 almost half 1536:1546 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 7 7 theme oligosaccharides 1509:1524 arg1 fucosylated 1557:1567 core fucosylated 1552:1567 core fucosylated 1552:1567 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 7 8 theme human 1444:1448 arg1 A 1474:1474 human placental arylsulfatase A 1444:1474 human placental arylsulfatase A 1444:1474 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 1 9 theme increased 456:464 arg1 sialylation 466:476 increased sialylation 456:476 increased sialylation 456:476 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 2 10 theme changes 548:554 arg1 significance 528:539 the significance 524:539 the significance of any changes in the glycosylation of arylsulfatase A in cancer 524:604 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 5 11 with MS 1193:1194 arg1 those 1251:1255 those 1251:1255 those 1251:1255 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 0 12 theme numerous 127:134 arg1 studies 136:142 numerous studies 127:142 numerous studies on arylsulfatase A 127:161 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 5 13 attach derived 1257:1263 arg2 those 1251:1255 those 1251:1255 those 1251:1255 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 5 13 attach derived 1257:1263 arg1 database 1281:1288 a sequence database 1270:1288 a sequence database 1270:1288 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 3 14 theme human 756:760 arg1 A 786:786 human placental arylsylfatase A 756:786 human placental arylsylfatase A 756:786 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 1 15 theme component 366:374 arg1 concentration 244:256 the concentration 240:256 the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells 240:444 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 6 16 theme arylsulfatase 1321:1333 arg1 A 1335:1335 arylsulfatase A 1321:1335 arylsulfatase A 1321:1335 Fifty picomoles (6 microg) of arylsulfatase A applied to the gel were sufficient to characterize its oligosaccharide content. 10814696 1 17 theme arylsulfatase 379:391 arg1 A 393:393 arylsulfatase A 379:393 arylsulfatase A 379:393 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 7 18 contain possesses 1476:1484 arg2 oligosaccharides 1509:1524 only high-mannose-type oligosaccharides 1486:1524 only high-mannose-type oligosaccharides 1486:1524 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 7 18 contain possesses 1476:1484 arg1 A 1474:1474 human placental arylsulfatase A 1444:1474 human placental arylsulfatase A 1444:1474 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 7 19 gly fucosylated 1557:1567 arg1 half 1543:1546 almost half 1536:1546 almost half 1536:1546 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 7 19 gly fucosylated 1557:1567 arg1 fucosylated 1557:1567 core fucosylated 1552:1567 core fucosylated 1552:1567 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 2 20 from structure 635:643 arg1 tissue 685:690 normal tissue 678:690 normal tissue 678:690 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 3 21 theme arylsylfatase 772:784 arg1 A 786:786 human placental arylsylfatase A 756:786 human placental arylsylfatase A 756:786 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 0 22 theme core 76:79 arg1 fucosylated 81:91 core fucosylated 76:91 core fucosylated 76:91 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 0 22 theme core 76:79 arg1 oligosaccharides 18:33 High-mannose-type oligosaccharides 0:33 High-mannose-type oligosaccharides from human placental arylsulfatase A 0:70 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 5 23 theme digestion 1151:1159 arg1 products 1161:1168 digestion products 1151:1168 digestion products 1151:1168 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 1 24 theme increases 277:285 arg1 concentration 244:256 the concentration 240:256 the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells 240:444 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 2 25 from component 665:673 arg1 tissue 685:690 normal tissue 678:690 normal tissue 678:690 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 3 26 theme gel 832:834 arg1 SDS-PAGE 853:860 SDS-PAGE 853:860 SDS-PAGE 853:860 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 3 26 theme gel 832:834 arg1 electrophoresis 836:850 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 794:850 sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release 794:967 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 1 27 with patients 309:316 arg1 forms 328:332 some forms 323:332 some forms of cancer 323:342 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 5 28 theme specific 1121:1128 arg1 exoglycosidases 1130:1144 specific exoglycosidases 1121:1144 specific exoglycosidases 1121:1144 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 0 29 gly fucosylated 81:91 arg1 oligosaccharides 18:33 High-mannose-type oligosaccharides 0:33 High-mannose-type oligosaccharides from human placental arylsulfatase A 0:70 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 0 29 gly fucosylated 81:91 arg1 fucosylated 81:91 core fucosylated 76:91 core fucosylated 76:91 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 0 30 from A 70:70 arg1 oligosaccharides 18:33 High-mannose-type oligosaccharides 0:33 High-mannose-type oligosaccharides from human placental arylsulfatase A 0:70 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 0 30 from A 70:70 arg1 fucosylated 81:91 core fucosylated 76:91 core fucosylated 76:91 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 2 31 from glycosylation 563:575 arg1 significance 528:539 the significance 524:539 the significance of any changes in the glycosylation of arylsulfatase A in cancer 524:604 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 2 31 from glycosylation 563:575 arg1 cancer 599:604 cancer 599:604 cancer 599:604 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 3 32 theme Immobilon 895:903 arg1 P 905:905 Immobilon P and on-blot deglycosylation 895:933 P 905:905 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 4 33 theme mass 1053:1056 arg1 spectrometry 1058:1069 matrix-assisted laser desorption/ionization mass spectrometry 1009:1069 matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) 1009:1080 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 4 33 theme mass 1053:1056 arg1 MS 1078:1079 MALDI MS 1072:1079 MALDI MS 1072:1079 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 2 34 theme carbohydrate 652:663 arg1 component 665:673 its carbohydrate component 648:673 its carbohydrate component in normal tissue 648:690 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 0 35 theme High-mannose-type 0:16 arg1 oligosaccharides 18:33 High-mannose-type oligosaccharides 0:33 High-mannose-type oligosaccharides from human placental arylsulfatase A 0:70 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 0 35 theme High-mannose-type 0:16 arg1 fucosylated 81:91 core fucosylated 76:91 core fucosylated 76:91 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 1 36 theme arylsulfatase 261:273 arg1 increases 277:285 arylsulfatase A increases 261:285 arylsulfatase A increases 261:285 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 3 37 theme PNGase 941:946 arg1 F 948:948 PNGase F 941:948 PNGase F for glycan release 941:967 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 5 38 theme matching 1213:1220 arg1 computer 1204:1211 the computer matching 1200:1220 the computer matching of the resulting masses with those derived from a sequence database 1200:1288 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 3 39 from blotting 883:890 arg1 P 905:905 Immobilon P and on-blot deglycosylation 895:933 P 905:905 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 3 39 from blotting 883:890 arg1 deglycosylation 919:933 Immobilon P and on-blot deglycosylation 895:933 deglycosylation 919:933 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 0 40 theme placental 46:54 arg1 A 70:70 human placental arylsulfatase A 40:70 human placental arylsulfatase A 40:70 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 4 41 theme laser 1025:1029 arg1 spectrometry 1058:1069 matrix-assisted laser desorption/ionization mass spectrometry 1009:1069 matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) 1009:1080 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 4 41 theme laser 1025:1029 arg1 MS 1078:1079 MALDI MS 1072:1079 MALDI MS 1072:1079 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 1 42 theme patients 309:316 arg1 fluids 299:304 the body fluids 290:304 the body fluids of patients with some forms of cancer 290:342 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 7 43 theme core 1552:1555 arg1 half 1543:1546 almost half 1536:1546 almost half 1536:1546 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 7 43 theme core 1552:1555 arg1 fucosylated 1557:1567 core fucosylated 1552:1567 core fucosylated 1552:1567 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 8 44 theme high-mannose-type 1612:1628 arg1 glycan 1630:1635 high-mannose-type glycan 1612:1635 high-mannose-type glycan bearing six mannose residues with a core fucose 1612:1683 In addition, there was a minor species of high-mannose-type glycan bearing six mannose residues with a core fucose. 10814696 2 45 from significance 528:539 arg1 glycosylation 563:575 the glycosylation 559:575 the glycosylation of arylsulfatase A in cancer 559:604 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 5 46 theme MALDI 1187:1191 arg1 MS 1193:1194 MALDI MS 1187:1194 MALDI MS 1187:1194 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 1 47 from fluids 299:304 arg1 concentration 244:256 the concentration 240:256 the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells 240:444 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 5 48 theme masses 1239:1244 arg1 MS 1193:1194 MALDI MS 1187:1194 MALDI MS 1187:1194 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 5 48 theme masses 1239:1244 arg1 computer 1204:1211 the computer matching 1200:1220 the computer matching of the resulting masses with those derived from a sequence database 1200:1288 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 7 49 theme high-mannose-type 1491:1507 arg1 oligosaccharides 1509:1524 only high-mannose-type oligosaccharides 1486:1524 only high-mannose-type oligosaccharides 1486:1524 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 2 50 theme arylsulfatase 580:592 arg1 A 594:594 arylsulfatase A 580:594 arylsulfatase A 580:594 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 8 51 theme core 1673:1676 arg1 fucose 1678:1683 a core fucose 1671:1683 a core fucose 1671:1683 In addition, there was a minor species of high-mannose-type glycan bearing six mannose residues with a core fucose. 10814696 1 52 from increases 277:285 arg1 fluids 299:304 the body fluids 290:304 the body fluids of patients with some forms of cancer 290:342 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 1 53 theme transformed 428:438 arg1 cells 440:444 transformed cells 428:444 transformed cells 428:444 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 7 54 theme placental 1450:1458 arg1 A 1474:1474 human placental arylsulfatase A 1444:1474 human placental arylsulfatase A 1444:1474 The results indicated that human placental arylsulfatase A possesses only high-mannose-type oligosaccharides, of which almost half are core fucosylated. 10814696 9 55 theme high-mannose-type 1724:1740 arg1 oligosaccharides 1742:1757 high-mannose-type oligosaccharides 1724:1757 high-mannose-type oligosaccharides 1724:1757 This structure was not expected since high-mannose-type oligosaccharides basically have not been recognized as a substrate for the alpha1,6-fucosyltransferase. 10814696 9 55 theme high-mannose-type 1724:1740 arg1 substrate 1799:1807 a substrate 1797:1807 a substrate for the alpha1,6-fucosyltransferase 1797:1843 This structure was not expected since high-mannose-type oligosaccharides basically have not been recognized as a substrate for the alpha1,6-fucosyltransferase. 10814696 2 56 from tissue 685:690 arg1 structure 635:643 the structure 631:643 the structure of its carbohydrate component in normal tissue 631:690 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 3 57 theme carbohydrate 731:742 arg1 moieties 744:751 carbohydrate moieties 731:751 carbohydrate moieties of human placental arylsylfatase A 731:786 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 1 58 from concentration 244:256 arg1 fluids 299:304 the body fluids 290:304 the body fluids of patients with some forms of cancer 290:342 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 5 59 with computer 1204:1211 arg1 those 1251:1255 those 1251:1255 those 1251:1255 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 0 60 theme arylsulfatase 147:159 arg1 A 161:161 arylsulfatase A 147:161 arylsulfatase A 147:161 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 1 61 theme carbohydrate 353:364 arg1 component 366:374 the carbohydrate component 349:374 the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells 349:444 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 3 62 theme placental 762:770 arg1 A 786:786 human placental arylsylfatase A 756:786 human placental arylsylfatase A 756:786 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 6 63 theme A 1335:1335 arg1 picomoles 1297:1305 Fifty picomoles 1291:1305 Fifty picomoles (6 microg) of arylsulfatase A applied to the gel 1291:1354 Fifty picomoles (6 microg) of arylsulfatase A applied to the gel were sufficient to characterize its oligosaccharide content. 10814696 6 63 theme A 1335:1335 arg1 microg 1310:1315 6 microg 1308:1315 6 microg 1308:1315 Fifty picomoles (6 microg) of arylsulfatase A applied to the gel were sufficient to characterize its oligosaccharide content. 10814696 2 64 gly glycosylation 563:575 arg1 cancer 599:604 cancer 599:604 cancer 599:604 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 2 64 gly glycosylation 563:575 arg1 A 594:594 arylsulfatase A 580:594 arylsulfatase A 580:594 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 2 65 theme normal 678:683 arg1 tissue 685:690 normal tissue 678:690 normal tissue 678:690 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 1 66 theme A 393:393 arg1 increases 277:285 arylsulfatase A increases 261:285 arylsulfatase A increases 261:285 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 1 66 theme A 393:393 arg1 component 366:374 the carbohydrate component 349:374 the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells 349:444 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 5 67 theme sequence 1272:1279 arg1 database 1281:1288 a sequence database 1270:1288 a sequence database 1270:1288 Oligosaccharides were sequenced using specific exoglycosidases, and digestion products were analyzed by MALDI MS and the computer matching of the resulting masses with those derived from a sequence database. 10814696 3 68 theme A 786:786 arg1 moieties 744:751 carbohydrate moieties 731:751 carbohydrate moieties of human placental arylsylfatase A 731:786 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 6 69 theme oligosaccharide 1392:1406 arg1 content 1408:1414 its oligosaccharide content 1388:1414 its oligosaccharide content 1388:1414 Fifty picomoles (6 microg) of arylsulfatase A applied to the gel were sufficient to characterize its oligosaccharide content. 10814696 4 70 theme N-glycans 982:990 arg1 Profiles 970:977 Profiles 970:977 Profiles of N-glycans 970:990 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 1 71 from component 366:374 arg1 fluids 299:304 the body fluids 290:304 the body fluids of patients with some forms of cancer 290:342 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 3 72 theme Western 875:881 arg1 blotting 883:890 Western blotting 875:890 Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release 875:967 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 1 73 gly sialylation 466:476 arg1 concentration 244:256 the concentration 240:256 the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells 240:444 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 3 74 theme sulfate-polyacrylamide 809:830 arg1 SDS-PAGE 853:860 SDS-PAGE 853:860 SDS-PAGE 853:860 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 3 74 theme sulfate-polyacrylamide 809:830 arg1 electrophoresis 836:850 sodium dodecyl sulfate-polyacrylamide gel electrophoresis 794:850 sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release 794:967 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 1 75 theme cancer 337:342 arg1 forms 328:332 some forms 323:332 some forms of cancer 323:342 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 3 76 theme on-blot 911:917 arg1 deglycosylation 919:933 Immobilon P and on-blot deglycosylation 895:933 deglycosylation 919:933 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 2 77 theme component 665:673 arg1 structure 635:643 the structure 631:643 the structure of its carbohydrate component in normal tissue 631:690 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 4 78 theme desorption/ionization 1031:1051 arg1 spectrometry 1058:1069 matrix-assisted laser desorption/ionization mass spectrometry 1009:1069 matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) 1009:1080 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 4 78 theme desorption/ionization 1031:1051 arg1 MS 1078:1079 MALDI MS 1072:1079 MALDI MS 1072:1079 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 0 79 theme human 40:44 arg1 A 70:70 human placental arylsulfatase A 40:70 human placental arylsulfatase A 40:70 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 1 80 theme A 275:275 arg1 increases 277:285 arylsulfatase A increases 261:285 arylsulfatase A increases 261:285 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 8 81 theme minor 1595:1599 arg1 species 1601:1607 a minor species 1593:1607 a minor species of high-mannose-type glycan bearing six mannose residues with a core fucose 1593:1683 In addition, there was a minor species of high-mannose-type glycan bearing six mannose residues with a core fucose. 10814696 0 82 theme arylsulfatase 56:68 arg1 A 70:70 human placental arylsulfatase A 40:70 human placental arylsulfatase A 40:70 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 0 83 from studies 136:142 arg1 A 161:161 arylsulfatase A 147:161 arylsulfatase A 147:161 High-mannose-type oligosaccharides from human placental arylsulfatase A are core fucosylated as confirmed by MALDI MS. Despite numerous studies on arylsulfatase A, the structure of its glycans is not well understood. 10814696 1 84 theme body 294:297 arg1 fluids 299:304 the body fluids 290:304 the body fluids of patients with some forms of cancer 290:342 It has been shown that the concentration of arylsulfatase A increases in the body fluids of patients with some forms of cancer, and the carbohydrate component of arylsulfatase A synthesized in tumor tissues and transformed cells undergoes increased sialylation, phosphorylation and sulfation. 10814696 4 85 theme matrix-assisted 1009:1023 arg1 spectrometry 1058:1069 matrix-assisted laser desorption/ionization mass spectrometry 1009:1069 matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) 1009:1080 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 4 85 theme matrix-assisted 1009:1023 arg1 MS 1078:1079 MALDI MS 1072:1079 MALDI MS 1072:1079 Profiles of N-glycans were obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). 10814696 8 86 theme glycan 1630:1635 arg1 species 1601:1607 a minor species 1593:1607 a minor species of high-mannose-type glycan bearing six mannose residues with a core fucose 1593:1683 In addition, there was a minor species of high-mannose-type glycan bearing six mannose residues with a core fucose. 10814696 3 87 theme glycan 954:959 arg1 release 961:967 glycan release 954:967 glycan release 954:967 In the present study we have analyzed carbohydrate moieties of human placental arylsylfatase A using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting on Immobilon P and on-blot deglycosylation using PNGase F for glycan release. 10814696 2 88 from changes 548:554 arg1 glycosylation 563:575 the glycosylation 559:575 the glycosylation of arylsulfatase A in cancer 559:604 To understand the significance of any changes in the glycosylation of arylsulfatase A in cancer, it is important to know the structure of its carbohydrate component in normal tissue. 10814696 8 89 theme mannose 1649:1655 arg1 residues 1657:1664 six mannose residues 1645:1664 six mannose residues 1645:1664 In addition, there was a minor species of high-mannose-type glycan bearing six mannose residues with a core fucose. 3342257 3 0 with analysis 567:574 arg1 spectrometry 612:623 gas-liquid chromatography-mass spectrometry 581:623 gas-liquid chromatography-mass spectrometry 581:623 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 1 1 attach linked 113:118 arg2 chains 106:111 The carbohydrate chains 89:111 The carbohydrate chains linked to human kappa-casein from mature milk 89:157 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 1 1 attach linked 113:118 arg2 oligosaccharides 218:233 reduced oligosaccharides 210:233 reduced oligosaccharides 210:233 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 1 1 attach linked 113:118 arg1 kappa-casein 129:140 human kappa-casein 123:140 human kappa-casein from mature milk 123:157 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 0 2 theme milk 70:73 arg1 kappa-casein 75:86 human mature milk kappa-casein 57:86 human mature milk kappa-casein 57:86 Chemical structure of neutral sugar chains isolated from human mature milk kappa-casein. 3342257 3 3 theme 13C 653:655 arg1 resonance 674:682 13C nuclear magnetic resonance 653:682 13C nuclear magnetic resonance 653:682 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 1 4 from milk 154:157 arg1 kappa-casein 129:140 human kappa-casein 123:140 human kappa-casein from mature milk 123:157 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 3 5 theme neutral 391:397 arg1 % 506:506 10.9% 502:506 10.9% 502:506 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 3 5 theme neutral 391:397 arg1 oligosaccharides 399:414 Seven neutral oligosaccharides 385:414 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] 385:507 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 3 6 theme nuclear 657:663 arg1 resonance 674:682 13C nuclear magnetic resonance 653:682 13C nuclear magnetic resonance 653:682 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 4 7 theme novel 1327:1331 arg1 alditols 1299:1306 Five oligosaccharide alditols 1278:1306 Five oligosaccharide alditols (III-VII) 1278:1316 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 4 7 theme novel 1327:1331 arg1 chains 1346:1351 the novel carbohydrate chains 1323:1351 the novel carbohydrate chains of kappa-casein from mammalian milk 1323:1387 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 4 8 theme oligosaccharide 1283:1297 arg1 chains 1346:1351 the novel carbohydrate chains 1323:1351 the novel carbohydrate chains of kappa-casein from mammalian milk 1323:1387 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 4 8 theme oligosaccharide 1283:1297 arg1 III-VII 1309:1315 III-VII 1309:1315 III-VII 1309:1315 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 4 8 theme oligosaccharide 1283:1297 arg1 alditols 1299:1306 Five oligosaccharide alditols 1278:1306 Five oligosaccharide alditols (III-VII) 1278:1316 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 4 9 theme carbohydrate 1333:1344 arg1 alditols 1299:1306 Five oligosaccharide alditols 1278:1306 Five oligosaccharide alditols (III-VII) 1278:1316 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 4 9 theme carbohydrate 1333:1344 arg1 chains 1346:1351 the novel carbohydrate chains 1323:1351 the novel carbohydrate chains of kappa-casein from mammalian milk 1323:1387 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 3 10 with analysis 639:646 arg1 resonance 674:682 13C nuclear magnetic resonance 653:682 13C nuclear magnetic resonance 653:682 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 1 11 theme alkaline 176:183 arg1 treatment 197:205 alkaline borohydride treatment 176:205 alkaline borohydride treatment 176:205 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 0 12 theme Chemical 0:7 arg1 structure 9:17 Chemical structure 0:17 Chemical structure of neutral sugar chains 0:41 Chemical structure of neutral sugar chains isolated from human mature milk kappa-casein. 3342257 1 13 theme borohydride 185:195 arg1 treatment 197:205 alkaline borohydride treatment 176:205 alkaline borohydride treatment 176:205 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 0 14 theme neutral 22:28 arg1 chains 36:41 neutral sugar chains 22:41 neutral sugar chains 22:41 Chemical structure of neutral sugar chains isolated from human mature milk kappa-casein. 3342257 4 15 theme mammalian 1374:1382 arg1 milk 1384:1387 mammalian milk 1374:1387 mammalian milk 1374:1387 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 2 16 theme gel 325:327 arg1 filtration 329:338 gel filtration 325:338 gel filtration 325:338 The neutral oligosaccharides of lower molecular weight were fractionated and purified by gel filtration and preparative thin layer chromatographies. 3342257 0 17 theme chains 36:41 arg1 structure 9:17 Chemical structure 0:17 Chemical structure of neutral sugar chains 0:41 Chemical structure of neutral sugar chains isolated from human mature milk kappa-casein. 3342257 1 18 theme reduced 210:216 arg1 chains 106:111 The carbohydrate chains 89:111 The carbohydrate chains linked to human kappa-casein from mature milk 89:157 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 1 18 theme reduced 210:216 arg1 oligosaccharides 218:233 reduced oligosaccharides 210:233 reduced oligosaccharides 210:233 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 0 19 theme sugar 30:34 arg1 chains 36:41 neutral sugar chains 22:41 neutral sugar chains 22:41 Chemical structure of neutral sugar chains isolated from human mature milk kappa-casein. 3342257 3 20 theme gas-liquid 581:590 arg1 spectrometry 612:623 gas-liquid chromatography-mass spectrometry 581:623 gas-liquid chromatography-mass spectrometry 581:623 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 2 21 theme neutral 240:246 arg1 oligosaccharides 248:263 The neutral oligosaccharides 236:263 The neutral oligosaccharides of lower molecular weight 236:289 The neutral oligosaccharides of lower molecular weight were fractionated and purified by gel filtration and preparative thin layer chromatographies. 3342257 3 22 theme chromatography-mass 592:610 arg1 spectrometry 612:623 gas-liquid chromatography-mass spectrometry 581:623 gas-liquid chromatography-mass spectrometry 581:623 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 2 23 theme layer 361:365 arg1 chromatographies 367:382 preparative thin layer chromatographies 344:382 preparative thin layer chromatographies 344:382 The neutral oligosaccharides of lower molecular weight were fractionated and purified by gel filtration and preparative thin layer chromatographies. 3342257 4 24 from milk 1384:1387 arg1 alditols 1299:1306 Five oligosaccharide alditols 1278:1306 Five oligosaccharide alditols (III-VII) 1278:1316 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 4 24 from milk 1384:1387 arg1 chains 1346:1351 the novel carbohydrate chains 1323:1351 the novel carbohydrate chains of kappa-casein from mammalian milk 1323:1387 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 4 25 theme kappa-casein 1356:1367 arg1 alditols 1299:1306 Five oligosaccharide alditols 1278:1306 Five oligosaccharide alditols (III-VII) 1278:1316 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 4 25 theme kappa-casein 1356:1367 arg1 chains 1346:1351 the novel carbohydrate chains 1323:1351 the novel carbohydrate chains of kappa-casein from mammalian milk 1323:1387 Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. 3342257 2 26 theme weight 284:289 arg1 oligosaccharides 248:263 The neutral oligosaccharides 236:263 The neutral oligosaccharides of lower molecular weight 236:289 The neutral oligosaccharides of lower molecular weight were fractionated and purified by gel filtration and preparative thin layer chromatographies. 3342257 3 27 dep tetra- 435:440 arg1 alditols 492:499 alditols 492:499 alditols 492:499 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 1 28 theme human 123:127 arg1 kappa-casein 129:140 human kappa-casein 123:140 human kappa-casein from mature milk 123:157 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 1 29 theme carbohydrate 93:104 arg1 oligosaccharides 218:233 reduced oligosaccharides 210:233 reduced oligosaccharides 210:233 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 1 29 theme carbohydrate 93:104 arg1 chains 106:111 The carbohydrate chains 89:111 The carbohydrate chains linked to human kappa-casein from mature milk 89:157 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 3342257 3 30 dep oligosaccharides 399:414 arg1 di- 419:421 a di- 417:421 a di- (0.5%) 417:428 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 3 30 dep oligosaccharides 399:414 arg1 % 427:427 0.5% 424:427 0.5% 424:427 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 3 30 dep oligosaccharides 399:414 arg1 penta- 455:460 penta- 455:460 penta- 455:460 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 3 30 dep oligosaccharides 399:414 arg1 tetra- 435:440 tetra- 435:440 tetra- 435:440 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 3 30 dep oligosaccharides 399:414 arg1 hexasaccharide 477:490 two hexasaccharide 473:490 two hexasaccharide 473:490 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 2 31 theme molecular 274:282 arg1 weight 284:289 lower molecular weight 268:289 lower molecular weight 268:289 The neutral oligosaccharides of lower molecular weight were fractionated and purified by gel filtration and preparative thin layer chromatographies. 3342257 2 32 theme preparative 344:354 arg1 chromatographies 367:382 preparative thin layer chromatographies 344:382 preparative thin layer chromatographies 344:382 The neutral oligosaccharides of lower molecular weight were fractionated and purified by gel filtration and preparative thin layer chromatographies. 3342257 2 33 theme thin 356:359 arg1 chromatographies 367:382 preparative thin layer chromatographies 344:382 preparative thin layer chromatographies 344:382 The neutral oligosaccharides of lower molecular weight were fractionated and purified by gel filtration and preparative thin layer chromatographies. 3342257 0 34 theme mature 63:68 arg1 kappa-casein 75:86 human mature milk kappa-casein 57:86 human mature milk kappa-casein 57:86 Chemical structure of neutral sugar chains isolated from human mature milk kappa-casein. 3342257 3 35 theme anomer 632:637 arg1 analysis 639:646 anomer analysis 632:646 anomer analysis with 13C nuclear magnetic resonance 632:682 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 2 36 theme lower 268:272 arg1 weight 284:289 lower molecular weight 268:289 lower molecular weight 268:289 The neutral oligosaccharides of lower molecular weight were fractionated and purified by gel filtration and preparative thin layer chromatographies. 3342257 0 37 theme human 57:61 arg1 kappa-casein 75:86 human mature milk kappa-casein 57:86 human mature milk kappa-casein 57:86 Chemical structure of neutral sugar chains isolated from human mature milk kappa-casein. 3342257 3 38 theme magnetic 665:672 arg1 resonance 674:682 13C nuclear magnetic resonance 653:682 13C nuclear magnetic resonance 653:682 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 3 39 theme methylation 555:565 arg1 analysis 567:574 methylation analysis 555:574 methylation analysis with gas-liquid chromatography-mass spectrometry 555:623 Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. 3342257 1 40 theme mature 147:152 arg1 milk 154:157 mature milk 147:157 mature milk 147:157 The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. 6155378 2 0 from carbohydrate 237:248 arg1 free 227:230 free 227:230 free 227:230 Isoenzymes in family B were free from carbohydrate, while those in family A were all glycoproteins. 6155378 5 1 theme radioactive 606:616 arg1 oligosaccharides 618:633 The radioactive oligosaccharides 602:633 The radioactive oligosaccharides 602:633 The radioactive oligosaccharides were fractionated into one acidic and two neutral oligosaccharide fractions by paper electrophoresis and paper chromatography. 6155378 4 2 theme A 522:522 arg1 isoenzymes 524:533 family A isoenzymes 515:533 family A isoenzymes 515:533 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 0 3 theme Structural 0:9 arg1 studies 11:17 Structural studies 0:17 Structural studies of the sugar chains of human parotid alpha-amylase 0:68 Structural studies of the sugar chains of human parotid alpha-amylase. 6155378 5 4 theme paper 714:718 arg1 electrophoresis 720:734 paper electrophoresis 714:734 paper electrophoresis 714:734 The radioactive oligosaccharides were fractionated into one acidic and two neutral oligosaccharide fractions by paper electrophoresis and paper chromatography. 6155378 3 5 theme polypeptide 373:383 arg1 portions 385:392 their polypeptide portions 367:392 their polypeptide portions 367:392 The carbohydrate moieties of family A isoenzymes were released from their polypeptide portions by hydrazinolysis and labeled by reduction with NaB[3H]4. 6155378 1 6 theme Human 71:75 arg1 amylase 85:91 Human parotid amylase 71:91 Human parotid amylase 71:91 Human parotid amylase can be separated into three families of isoenzymes (A', A, and B) by Sephadex G-75 column chromatography. 6155378 1 7 theme parotid 77:83 arg1 amylase 85:91 Human parotid amylase 71:91 Human parotid amylase 71:91 Human parotid amylase can be separated into three families of isoenzymes (A', A, and B) by Sephadex G-75 column chromatography. 6155378 3 8 theme family 328:333 arg1 isoenzymes 337:346 family A isoenzymes 328:346 family A isoenzymes 328:346 The carbohydrate moieties of family A isoenzymes were released from their polypeptide portions by hydrazinolysis and labeled by reduction with NaB[3H]4. 6155378 2 9 from Isoenzymes 199:208 arg1 B 220:220 family B 213:220 family B 213:220 Isoenzymes in family B were free from carbohydrate, while those in family A were all glycoproteins. 6155378 3 10 theme carbohydrate 303:314 arg1 moieties 316:323 The carbohydrate moieties 299:323 The carbohydrate moieties of family A isoenzymes 299:346 The carbohydrate moieties of family A isoenzymes were released from their polypeptide portions by hydrazinolysis and labeled by reduction with NaB[3H]4. 6155378 4 11 theme oligosaccharides 483:498 arg1 yield 456:460 The yield 452:460 The yield of total radioactive oligosaccharides 452:498 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 4 12 theme family 515:520 arg1 isoenzymes 524:533 family A isoenzymes 515:533 family A isoenzymes 515:533 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 4 13 theme asparagine-linked 554:570 arg1 chains 578:583 single asparagine-linked sugar chains 547:583 single asparagine-linked sugar chains 547:583 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 3 14 attach released 353:360 arg1 portions 385:392 their polypeptide portions 367:392 their polypeptide portions 367:392 The carbohydrate moieties of family A isoenzymes were released from their polypeptide portions by hydrazinolysis and labeled by reduction with NaB[3H]4. 6155378 3 14 attach released 353:360 arg2 moieties 316:323 The carbohydrate moieties 299:323 The carbohydrate moieties of family A isoenzymes 299:346 The carbohydrate moieties of family A isoenzymes were released from their polypeptide portions by hydrazinolysis and labeled by reduction with NaB[3H]4. 6155378 1 15 dep isoenzymes 133:142 arg1 A 149:149 A 149:149 A 149:149 Human parotid amylase can be separated into three families of isoenzymes (A', A, and B) by Sephadex G-75 column chromatography. 6155378 1 15 dep isoenzymes 133:142 arg1 B 156:156 B 156:156 B 156:156 Human parotid amylase can be separated into three families of isoenzymes (A', A, and B) by Sephadex G-75 column chromatography. 6155378 1 15 dep isoenzymes 133:142 arg1 isoenzymes 133:142 isoenzymes 133:142 isoenzymes (A', A, and B) 133:157 Human parotid amylase can be separated into three families of isoenzymes (A', A, and B) by Sephadex G-75 column chromatography. 6155378 1 15 dep isoenzymes 133:142 arg1 A 145:145 A' 145:146 A' 145:146 Human parotid amylase can be separated into three families of isoenzymes (A', A, and B) by Sephadex G-75 column chromatography. 6155378 0 16 theme chains 32:37 arg1 studies 11:17 Structural studies 0:17 Structural studies of the sugar chains of human parotid alpha-amylase 0:68 Structural studies of the sugar chains of human parotid alpha-amylase. 6155378 5 17 theme neutral 677:683 arg1 fractions 701:709 two neutral oligosaccharide fractions 673:709 two neutral oligosaccharide fractions 673:709 The radioactive oligosaccharides were fractionated into one acidic and two neutral oligosaccharide fractions by paper electrophoresis and paper chromatography. 6155378 5 18 theme oligosaccharide 685:699 arg1 fractions 701:709 two neutral oligosaccharide fractions 673:709 two neutral oligosaccharide fractions 673:709 The radioactive oligosaccharides were fractionated into one acidic and two neutral oligosaccharide fractions by paper electrophoresis and paper chromatography. 6155378 0 19 theme sugar 26:30 arg1 chains 32:37 the sugar chains 22:37 the sugar chains of human parotid alpha-amylase 22:68 Structural studies of the sugar chains of human parotid alpha-amylase. 6155378 2 20 gly glycoproteins 284:296 arg1 glycoproteins 284:296 all glycoproteins 280:296 all glycoproteins 280:296 Isoenzymes in family B were free from carbohydrate, while those in family A were all glycoproteins. 6155378 4 21 link asparagine-linked 554:570 arg1 chains 578:583 single asparagine-linked sugar chains 547:583 single asparagine-linked sugar chains 547:583 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 4 22 contain contain 539:545 arg2 chains 578:583 single asparagine-linked sugar chains 547:583 single asparagine-linked sugar chains 547:583 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 4 22 contain contain 539:545 arg1 molecule 592:599 one molecule 588:599 one molecule 588:599 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 4 22 contain contain 539:545 arg1 isoenzymes 524:533 family A isoenzymes 515:533 family A isoenzymes 515:533 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 4 22 contain contain 539:545 arg2 isoenzymes 524:533 family A isoenzymes 515:533 family A isoenzymes 515:533 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 3 23 theme A 335:335 arg1 isoenzymes 337:346 family A isoenzymes 328:346 family A isoenzymes 328:346 The carbohydrate moieties of family A isoenzymes were released from their polypeptide portions by hydrazinolysis and labeled by reduction with NaB[3H]4. 6155378 0 24 theme parotid 48:54 arg1 alpha-amylase 56:68 human parotid alpha-amylase 42:68 human parotid alpha-amylase 42:68 Structural studies of the sugar chains of human parotid alpha-amylase. 6155378 3 25 theme isoenzymes 337:346 arg1 moieties 316:323 The carbohydrate moieties 299:323 The carbohydrate moieties of family A isoenzymes 299:346 The carbohydrate moieties of family A isoenzymes were released from their polypeptide portions by hydrazinolysis and labeled by reduction with NaB[3H]4. 6155378 4 26 theme radioactive 471:481 arg1 oligosaccharides 483:498 total radioactive oligosaccharides 465:498 total radioactive oligosaccharides 465:498 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 4 27 theme total 465:469 arg1 oligosaccharides 483:498 total radioactive oligosaccharides 465:498 total radioactive oligosaccharides 465:498 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 2 28 theme family 213:218 arg1 B 220:220 family B 213:220 family B 213:220 Isoenzymes in family B were free from carbohydrate, while those in family A were all glycoproteins. 6155378 5 29 theme paper 740:744 arg1 chromatography 746:759 paper chromatography 740:759 paper chromatography 740:759 The radioactive oligosaccharides were fractionated into one acidic and two neutral oligosaccharide fractions by paper electrophoresis and paper chromatography. 6155378 2 30 theme family 266:271 arg1 A 273:273 family A 266:273 family A 266:273 Isoenzymes in family B were free from carbohydrate, while those in family A were all glycoproteins. 6155378 1 31 theme Sephadex 162:169 arg1 chromatography 183:196 Sephadex G-75 column chromatography 162:196 Sephadex G-75 column chromatography 162:196 Human parotid amylase can be separated into three families of isoenzymes (A', A, and B) by Sephadex G-75 column chromatography. 6155378 1 32 theme G-75 171:174 arg1 chromatography 183:196 Sephadex G-75 column chromatography 162:196 Sephadex G-75 column chromatography 162:196 Human parotid amylase can be separated into three families of isoenzymes (A', A, and B) by Sephadex G-75 column chromatography. 6155378 0 33 theme alpha-amylase 56:68 arg1 chains 32:37 the sugar chains 22:37 the sugar chains of human parotid alpha-amylase 22:68 Structural studies of the sugar chains of human parotid alpha-amylase. 6155378 1 34 theme column 176:181 arg1 chromatography 183:196 Sephadex G-75 column chromatography 162:196 Sephadex G-75 column chromatography 162:196 Human parotid amylase can be separated into three families of isoenzymes (A', A, and B) by Sephadex G-75 column chromatography. 6155378 0 35 theme human 42:46 arg1 alpha-amylase 56:68 human parotid alpha-amylase 42:68 human parotid alpha-amylase 42:68 Structural studies of the sugar chains of human parotid alpha-amylase. 6155378 4 36 theme single 547:552 arg1 chains 578:583 single asparagine-linked sugar chains 547:583 single asparagine-linked sugar chains 547:583 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 6155378 1 37 theme isoenzymes 133:142 arg1 families 121:128 three families 115:128 three families of isoenzymes (A', A, and B) 115:157 Human parotid amylase can be separated into three families of isoenzymes (A', A, and B) by Sephadex G-75 column chromatography. 6155378 4 38 theme sugar 572:576 arg1 chains 578:583 single asparagine-linked sugar chains 547:583 single asparagine-linked sugar chains 547:583 The yield of total radioactive oligosaccharides indicated that family A isoenzymes all contain single asparagine-linked sugar chains in one molecule. 2015821 4 0 theme triantennary 917:928 arg1 oligosaccharide 930:944 disialylated triantennary oligosaccharide 904:944 disialylated triantennary oligosaccharide 904:944 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 1 1 theme human 187:191 arg1 serum 193:197 normal human serum 180:197 normal human serum 180:197 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 1 2 theme concanavalin-A-Sepharose 282:305 arg1 column 307:312 a concanavalin-A-Sepharose column 280:312 a concanavalin-A-Sepharose column 280:312 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 0 3 theme 1H-NMR 85:90 arg1 spectroscopy 92:103 1H-NMR spectroscopy 85:103 1H-NMR spectroscopy 85:103 Structure determination of the glycans of human-serum alpha 1-antichymotrypsin using 1H-NMR spectroscopy and deglycosylation by N-glycanase. 2015821 4 4 theme disialylated 904:915 arg1 oligosaccharide 930:944 disialylated triantennary oligosaccharide 904:944 disialylated triantennary oligosaccharide 904:944 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 4 5 theme oligosaccharide 930:944 arg1 traces 894:899 traces 894:899 traces of disialylated triantennary oligosaccharide 894:944 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 3 6 theme high-resolution 710:724 arg1 spectroscopy 733:744 high-resolution 1H-NMR spectroscopy 710:744 high-resolution 1H-NMR spectroscopy 710:744 The complete primary structure of the glycans was determined by high-resolution 1H-NMR spectroscopy. 2015821 8 7 contain carrying 1680:1687 arg1 molecules 1670:1678 molecules 1670:1678 molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans 1670:1799 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 8 7 contain carrying 1680:1687 arg2 glycans 1793:1799 three diantennary glycans 1775:1799 three diantennary glycans 1775:1799 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 8 7 contain carrying 1680:1687 arg2 others 1738:1743 others 1738:1743 others carrying one triantennary 1738:1769 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 8 7 contain carrying 1680:1687 arg2 glycans 1726:1732 two diantennary glycans 1710:1732 two diantennary glycans 1710:1732 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 5 8 link N-linked 1074:1081 arg1 chains 1117:1122 the N-linked complex-type oligosaccharide side chains 1070:1122 the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin 1070:1150 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 5 9 theme detergents 1183:1192 arg1 presence 1171:1178 the presence 1167:1178 the presence of detergents 1167:1192 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 2 10 theme affinity 584:591 arg1 chromatography 593:606 affinity chromatography 584:606 affinity chromatography on a concanavalin-A-Sepharose column 584:643 For each form the asparagine-linked carbohydrate chains were liberated as oligosaccharides by hydrazinolysis, submitted to reduction with NaBH4 after re-N-acetylation and further separated by affinity chromatography on a concanavalin-A-Sepharose column. 2015821 2 11 link asparagine-linked 410:426 arg1 chains 441:446 the asparagine-linked carbohydrate chains 406:446 the asparagine-linked carbohydrate chains 406:446 For each form the asparagine-linked carbohydrate chains were liberated as oligosaccharides by hydrazinolysis, submitted to reduction with NaBH4 after re-N-acetylation and further separated by affinity chromatography on a concanavalin-A-Sepharose column. 2015821 4 12 theme diantennary 794:804 arg1 presence 773:780 the presence 769:780 the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures 769:859 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 6 13 contain carries 1264:1270 arg1 1-antichymotrypsin 1245:1262 alpha 1-antichymotrypsin 1239:1262 alpha 1-antichymotrypsin 1239:1262 From these experiments it is concluded that alpha 1-antichymotrypsin carries four oligosaccharide side chains. 2015821 6 13 contain carries 1264:1270 arg2 chains 1298:1303 four oligosaccharide side chains 1272:1303 four oligosaccharide side chains 1272:1303 From these experiments it is concluded that alpha 1-antichymotrypsin carries four oligosaccharide side chains. 2015821 7 14 contain possess 1470:1476 arg1 peaks 1458:1462 the bound peaks 3 + 4 1448:1468 the bound peaks 3 + 4 1448:1468 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 7 14 contain possess 1470:1476 arg2 triantennary 1501:1512 about one triantennary 1491:1512 about one triantennary 1491:1512 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 7 14 contain possess 1470:1476 arg2 glycans 1536:1542 three diantennary glycans 1518:1542 three diantennary glycans per molecule 1518:1555 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 4 15 theme trisialyl 813:821 arg1 structures 850:859 trisialyl triantennary type glycanic structures 813:859 trisialyl triantennary type glycanic structures 813:859 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 4 16 gly disialylated 904:915 arg1 oligosaccharide 930:944 disialylated triantennary oligosaccharide 904:944 disialylated triantennary oligosaccharide 904:944 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 0 17 theme human-serum 42:52 arg1 1-antichymotrypsin 60:77 human-serum alpha 1-antichymotrypsin 42:77 human-serum alpha 1-antichymotrypsin 42:77 Structure determination of the glycans of human-serum alpha 1-antichymotrypsin using 1H-NMR spectroscopy and deglycosylation by N-glycanase. 2015821 1 18 theme bound 366:370 arg1 peaks 378:382 peaks 3 + 4 378:388 peaks 3 + 4 378:388 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 1 18 theme bound 366:370 arg1 form 372:375 a bound form 364:375 a bound form (peaks 3 + 4) 364:389 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 6 19 theme alpha 1239:1243 arg1 1-antichymotrypsin 1245:1262 alpha 1-antichymotrypsin 1239:1262 alpha 1-antichymotrypsin 1239:1262 From these experiments it is concluded that alpha 1-antichymotrypsin carries four oligosaccharide side chains. 2015821 8 20 contain contains 1590:1597 arg2 glycans 1618:1624 diantennary glycans 1606:1624 diantennary glycans 1606:1624 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 8 20 contain contains 1590:1597 arg1 4 1588:1588 4 1588:1588 4 1588:1588 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 2 21 theme asparagine-linked 410:426 arg1 chains 441:446 the asparagine-linked carbohydrate chains 406:446 the asparagine-linked carbohydrate chains 406:446 For each form the asparagine-linked carbohydrate chains were liberated as oligosaccharides by hydrazinolysis, submitted to reduction with NaBH4 after re-N-acetylation and further separated by affinity chromatography on a concanavalin-A-Sepharose column. 2015821 8 22 theme diantennary 1606:1616 arg1 glycans 1618:1624 diantennary glycans 1606:1624 diantennary glycans 1606:1624 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 8 23 theme diantennary 1781:1791 arg1 glycans 1793:1799 three diantennary glycans 1775:1799 three diantennary glycans 1775:1799 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 0 24 theme Structure 0:8 arg1 determination 10:22 Structure determination 0:22 Structure determination of the glycans of human-serum alpha 1-antichymotrypsin 0:77 Structure determination of the glycans of human-serum alpha 1-antichymotrypsin using 1H-NMR spectroscopy and deglycosylation by N-glycanase. 2015821 2 25 from chromatography 593:606 arg1 column 638:643 a concanavalin-A-Sepharose column 611:643 a concanavalin-A-Sepharose column 611:643 For each form the asparagine-linked carbohydrate chains were liberated as oligosaccharides by hydrazinolysis, submitted to reduction with NaBH4 after re-N-acetylation and further separated by affinity chromatography on a concanavalin-A-Sepharose column. 2015821 2 26 theme concanavalin-A-Sepharose 613:636 arg1 column 638:643 a concanavalin-A-Sepharose column 611:643 a concanavalin-A-Sepharose column 611:643 For each form the asparagine-linked carbohydrate chains were liberated as oligosaccharides by hydrazinolysis, submitted to reduction with NaBH4 after re-N-acetylation and further separated by affinity chromatography on a concanavalin-A-Sepharose column. 2015821 2 27 with reduction 515:523 arg1 NaBH4 530:534 NaBH4 530:534 NaBH4 530:534 For each form the asparagine-linked carbohydrate chains were liberated as oligosaccharides by hydrazinolysis, submitted to reduction with NaBH4 after re-N-acetylation and further separated by affinity chromatography on a concanavalin-A-Sepharose column. 2015821 5 28 theme unfractionated 1003:1016 arg1 1-antichymotrypsin 1024:1041 the unfractionated alpha 1-antichymotrypsin 999:1041 the unfractionated alpha 1-antichymotrypsin 999:1041 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 8 29 contain carrying 1745:1752 arg2 triantennary 1758:1769 one triantennary 1754:1769 one triantennary 1754:1769 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 8 29 contain carrying 1745:1752 arg1 others 1738:1743 others 1738:1743 others carrying one triantennary 1738:1769 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 1 30 theme affinity 216:223 arg1 chromatography 225:238 affinity chromatography 216:238 affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column 216:312 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 5 31 theme N-linked 1074:1081 arg1 chains 1117:1122 the N-linked complex-type oligosaccharide side chains 1070:1122 the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin 1070:1150 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 7 32 theme bound 1452:1456 arg1 peaks 1458:1462 the bound peaks 3 + 4 1448:1468 the bound peaks 3 + 4 1448:1468 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 4 33 theme disialyl 785:792 arg1 diantennary 794:804 disialyl diantennary 785:804 disialyl diantennary 785:804 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 5 34 theme oligosaccharide 1096:1110 arg1 chains 1117:1122 the N-linked complex-type oligosaccharide side chains 1070:1122 the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin 1070:1150 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 5 35 theme successive 1048:1057 arg1 removal 1059:1065 the successive removal 1044:1065 the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin 1044:1150 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 5 36 theme 1-antichymotrypsin 1024:1041 arg1 deglycosylation 980:994 the deglycosylation 976:994 the deglycosylation of the unfractionated alpha 1-antichymotrypsin 976:1041 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 7 37 theme peak 1388:1391 arg1 triantennary 1401:1412 the peak 2 three triantennary 1384:1412 the peak 2 three triantennary 1384:1412 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 7 38 dep peaks 1458:1462 arg1 4 1468:1468 4 1468:1468 4 1468:1468 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 7 38 dep peaks 1458:1462 arg1 3 1464:1464 3 1464:1464 3 1464:1464 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 5 39 used used 967:970 arg2 N-glycanase 951:961 The N-glycanase 947:961 The N-glycanase 947:961 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 7 40 theme diantennary 1422:1432 arg1 glycans 1434:1440 one diantennary glycans 1418:1440 one diantennary glycans 1418:1440 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 1 41 theme th 245:246 arg1 forms 271:275 th ree microheterogeneous forms 245:275 th ree microheterogeneous forms 245:275 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 0 42 theme glycans 31:37 arg1 determination 10:22 Structure determination 0:22 Structure determination of the glycans of human-serum alpha 1-antichymotrypsin 0:77 Structure determination of the glycans of human-serum alpha 1-antichymotrypsin using 1H-NMR spectroscopy and deglycosylation by N-glycanase. 2015821 5 43 gly deglycosylation 980:994 arg1 1-antichymotrypsin 1024:1041 the unfractionated alpha 1-antichymotrypsin 999:1041 the unfractionated alpha 1-antichymotrypsin 999:1041 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 3 44 theme complete 650:657 arg1 structure 667:675 The complete primary structure 646:675 The complete primary structure of the glycans 646:690 The complete primary structure of the glycans was determined by high-resolution 1H-NMR spectroscopy. 2015821 5 45 theme side 1112:1115 arg1 chains 1117:1122 the N-linked complex-type oligosaccharide side chains 1070:1122 the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin 1070:1150 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 0 46 theme alpha 54:58 arg1 1-antichymotrypsin 60:77 human-serum alpha 1-antichymotrypsin 42:77 human-serum alpha 1-antichymotrypsin 42:77 Structure determination of the glycans of human-serum alpha 1-antichymotrypsin using 1H-NMR spectroscopy and deglycosylation by N-glycanase. 2015821 2 47 dep oligosaccharides 466:481 arg1 submitted 502:510 submitted 502:510 submitted to reduction with NaBH4 after re-N-acetylation 502:557 For each form the asparagine-linked carbohydrate chains were liberated as oligosaccharides by hydrazinolysis, submitted to reduction with NaBH4 after re-N-acetylation and further separated by affinity chromatography on a concanavalin-A-Sepharose column. 2015821 2 47 dep oligosaccharides 466:481 arg1 separated 571:579 separated 571:579 further separated by affinity chromatography on a concanavalin-A-Sepharose column 563:643 For each form the asparagine-linked carbohydrate chains were liberated as oligosaccharides by hydrazinolysis, submitted to reduction with NaBH4 after re-N-acetylation and further separated by affinity chromatography on a concanavalin-A-Sepharose column. 2015821 3 48 theme primary 659:665 arg1 structure 667:675 The complete primary structure 646:675 The complete primary structure of the glycans 646:690 The complete primary structure of the glycans was determined by high-resolution 1H-NMR spectroscopy. 2015821 5 49 theme chains 1117:1122 arg1 removal 1059:1065 the successive removal 1044:1065 the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin 1044:1150 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 7 50 theme diantennary 1524:1534 arg1 glycans 1536:1542 three diantennary glycans 1518:1542 three diantennary glycans per molecule 1518:1555 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 2 51 theme carbohydrate 428:439 arg1 chains 441:446 the asparagine-linked carbohydrate chains 406:446 the asparagine-linked carbohydrate chains 406:446 For each form the asparagine-linked carbohydrate chains were liberated as oligosaccharides by hydrazinolysis, submitted to reduction with NaBH4 after re-N-acetylation and further separated by affinity chromatography on a concanavalin-A-Sepharose column. 2015821 6 52 theme side 1293:1296 arg1 chains 1298:1303 four oligosaccharide side chains 1272:1303 four oligosaccharide side chains 1272:1303 From these experiments it is concluded that alpha 1-antichymotrypsin carries four oligosaccharide side chains. 2015821 7 53 contain contains 1348:1355 arg1 1 1346:1346 1 1346:1346 1 1346:1346 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 7 53 contain contains 1348:1355 arg2 glycans 1434:1440 one diantennary glycans 1418:1440 one diantennary glycans 1418:1440 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 7 53 contain contains 1348:1355 arg2 glycans 1375:1381 four triantennary glycans 1357:1381 four triantennary glycans 1357:1381 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 7 53 contain contains 1348:1355 arg2 triantennary 1401:1412 the peak 2 three triantennary 1384:1412 the peak 2 three triantennary 1384:1412 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 5 54 theme alpha 1127:1131 arg1 1-antichymotrypsin 1133:1150 alpha 1-antichymotrypsin 1127:1150 alpha 1-antichymotrypsin 1127:1150 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 1 55 dep separated 203:211 arg1 retarded 342:349 retarded 342:349 retarded 342:349 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 1 55 dep separated 203:211 arg1 pass-through 317:328 pass-through 317:328 pass-through 317:328 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 1 55 dep separated 203:211 arg1 form 372:375 a bound form 364:375 a bound form (peaks 3 + 4) 364:389 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 1 55 dep separated 203:211 arg1 peak 331:334 peak 1 331:336 peak 1 331:336 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 1 55 dep separated 203:211 arg1 peak 352:355 peak 2 352:357 peak 2 352:357 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 1 55 dep separated 203:211 arg1 peaks 378:382 peaks 3 + 4 378:388 peaks 3 + 4 378:388 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 1 56 from chromatography 225:238 arg1 column 307:312 a concanavalin-A-Sepharose column 280:312 a concanavalin-A-Sepharose column 280:312 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 1 57 theme alpha 141:145 arg1 1-Antichymotrypsin 147:164 alpha 1-Antichymotrypsin 141:164 alpha 1-Antichymotrypsin purified from normal human serum 141:197 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 8 58 theme diantennary 1714:1724 arg1 glycans 1726:1732 two diantennary glycans 1710:1732 two diantennary glycans 1710:1732 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 5 59 theme complex-type 1083:1094 arg1 chains 1117:1122 the N-linked complex-type oligosaccharide side chains 1070:1122 the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin 1070:1150 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 5 60 theme 1-antichymotrypsin 1133:1150 arg1 chains 1117:1122 the N-linked complex-type oligosaccharide side chains 1070:1122 the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin 1070:1150 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 4 61 theme type 836:839 arg1 structures 850:859 trisialyl triantennary type glycanic structures 813:859 trisialyl triantennary type glycanic structures 813:859 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 8 62 theme triantennary 1693:1704 arg1 glycans 1726:1732 two diantennary glycans 1710:1732 two diantennary glycans 1710:1732 Since we showed that the peak 4 contains mostly diantennary glycans, it can be deduced that in peak 3 there are molecules carrying two triantennary and two diantennary glycans and others carrying one triantennary and three diantennary glycans. 2015821 5 63 theme alpha 1018:1022 arg1 1-antichymotrypsin 1024:1041 the unfractionated alpha 1-antichymotrypsin 999:1041 the unfractionated alpha 1-antichymotrypsin 999:1041 The N-glycanase was used for the deglycosylation of the unfractionated alpha 1-antichymotrypsin; the successive removal of the N-linked complex-type oligosaccharide side chains of alpha 1-antichymotrypsin was studied in the presence of detergents. 2015821 1 64 theme microheterogeneous 252:269 arg1 forms 271:275 th ree microheterogeneous forms 245:275 th ree microheterogeneous forms 245:275 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 2015821 4 65 theme triantennary 823:834 arg1 structures 850:859 trisialyl triantennary type glycanic structures 813:859 trisialyl triantennary type glycanic structures 813:859 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 7 66 theme triantennary 1362:1373 arg1 glycans 1375:1381 four triantennary glycans 1357:1381 four triantennary glycans 1357:1381 Moreover our results show that the peak 1 contains four triantennary glycans, the peak 2 three triantennary and one diantennary glycans while the bound peaks 3 + 4 possess, on average, about one triantennary and three diantennary glycans per molecule. 2015821 3 67 theme glycans 684:690 arg1 structure 667:675 The complete primary structure 646:675 The complete primary structure of the glycans 646:690 The complete primary structure of the glycans was determined by high-resolution 1H-NMR spectroscopy. 2015821 4 68 theme structures 850:859 arg1 presence 773:780 the presence 769:780 the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures 769:859 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 6 69 theme oligosaccharide 1277:1291 arg1 chains 1298:1303 four oligosaccharide side chains 1272:1303 four oligosaccharide side chains 1272:1303 From these experiments it is concluded that alpha 1-antichymotrypsin carries four oligosaccharide side chains. 2015821 0 70 theme 1-antichymotrypsin 60:77 arg1 glycans 31:37 the glycans 27:37 the glycans of human-serum alpha 1-antichymotrypsin 27:77 Structure determination of the glycans of human-serum alpha 1-antichymotrypsin using 1H-NMR spectroscopy and deglycosylation by N-glycanase. 2015821 3 71 theme 1H-NMR 726:731 arg1 spectroscopy 733:744 high-resolution 1H-NMR spectroscopy 710:744 high-resolution 1H-NMR spectroscopy 710:744 The complete primary structure of the glycans was determined by high-resolution 1H-NMR spectroscopy. 2015821 4 72 theme glycanic 841:848 arg1 structures 850:859 trisialyl triantennary type glycanic structures 813:859 trisialyl triantennary type glycanic structures 813:859 The results indicated the presence of disialyl diantennary and of trisialyl triantennary type glycanic structures, the latter being accompanied by traces of disialylated triantennary oligosaccharide. 2015821 1 73 theme normal 180:185 arg1 serum 193:197 normal human serum 180:197 normal human serum 180:197 alpha 1-Antichymotrypsin purified from normal human serum was separated by affinity chromatography into th ree microheterogeneous forms on a concanavalin-A-Sepharose column: a pass-through (peak 1), a retarded (peak 2) and a bound form (peaks 3 + 4). 8969451 6 0 theme resulting 1025:1033 arg1 patterns 1039:1046 The resulting gel patterns 1021:1046 The resulting gel patterns 1021:1046 The resulting gel patterns were interpreted, based on band mobility shifts, to obtain the sequence structure of the oligosaccharides. 8969451 10 1 link CHO-cell-derived 1805:1820 arg1 protein 1822:1828 the CHO-cell-derived protein 1801:1828 the CHO-cell-derived protein 1801:1828 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 11 2 theme luminance 1964:1972 arg1 data 1974:1977 percentage lane luminance data 1948:1977 percentage lane luminance data 1948:1977 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 1 3 theme Chinese-hamster 289:303 arg1 cells 317:321 Chinese-hamster ovary (CHO) cells 289:321 Chinese-hamster ovary (CHO) cells 289:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 8 4 link CHO-cell-derived 1365:1380 arg1 rFVIII 1382:1387 CHO-cell-derived rFVIII 1365:1387 CHO-cell-derived rFVIII 1365:1387 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 0 5 link N-linked 15:22 arg1 structures 40:49 N-linked oligosaccharide structures 15:49 N-linked oligosaccharide structures of recombinant human factor VIII 15:82 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII using fluorophore-assisted carbohydrate electrophoresis. 8969451 11 6 theme lane 1959:1962 arg1 data 1974:1977 percentage lane luminance data 1948:1977 percentage lane luminance data 1948:1977 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 4 7 theme fluorophore-assisted 764:783 arg1 FACE 815:818 FACE 815:818 FACE 815:818 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 4 7 theme fluorophore-assisted 764:783 arg1 electrophoresis 798:812 fluorophore-assisted carbohydrate electrophoresis 764:812 fluorophore-assisted carbohydrate electrophoresis (FACE) 764:819 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 7 8 theme structures 1194:1203 arg1 total 1157:1161 A total 1155:1161 A total of eight acidic and 12 neutral structures 1155:1203 A total of eight acidic and 12 neutral structures were identified, and the majority of the oligosaccharides (approximately 92%) were found to be sialylated. 8969451 3 9 theme N-linked 533:540 arg1 oligosaccharides 542:557 the N-linked oligosaccharides 529:557 the N-linked oligosaccharides 529:557 While N-linked and O-linked oligosaccharides are found in this protein, the current study focuses on the N-linked oligosaccharides. 8969451 1 10 theme manufacturing 210:222 arg1 consistency 232:242 manufacturing process consistency 210:242 manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells 210:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 4 11 theme fluorophore 696:706 arg1 8-aminonaphthalene-1,3,6-trisulphonate 708:745 the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate 692:745 the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate 692:745 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 5 12 theme exoglycosidases 957:971 arg1 pools 948:952 defined pools 940:952 defined pools of exoglycosidases 940:971 The electrophoretically resolved oligosaccharide bands were isolated and individual bands subjected to digestion with defined pools of exoglycosidases and re-electrophoresed on FACE sequencing gels. 8969451 1 13 theme consistency 232:242 arg1 Characterization 141:156 Characterization 141:156 Characterization of the carbohydrate moiety 141:183 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 1 13 theme consistency 232:242 arg1 measure 199:205 a critical measure 188:205 a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells 188:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 6 14 theme band 1075:1078 arg1 shifts 1089:1094 band mobility shifts 1075:1094 band mobility shifts 1075:1094 The resulting gel patterns were interpreted, based on band mobility shifts, to obtain the sequence structure of the oligosaccharides. 8969451 4 15 theme endoglycosidase 656:670 arg1 H 672:672 endoglycosidase H 656:672 endoglycosidase H 656:672 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 11 16 theme rFVIII 1896:1901 arg1 [coefficient 1903:1914 rFVIII [coefficient 1896:1914 rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides 1896:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 7 17 theme acidic 1172:1177 arg1 total 1157:1161 A total 1155:1161 A total of eight acidic and 12 neutral structures 1155:1203 A total of eight acidic and 12 neutral structures were identified, and the majority of the oligosaccharides (approximately 92%) were found to be sialylated. 8969451 1 18 theme recombinant 247:257 arg1 rFVIII 278:283 rFVIII 278:283 rFVIII 278:283 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 1 18 theme recombinant 247:257 arg1 VIII 272:275 recombinant human Factor VIII 247:275 recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells 247:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 11 19 from lots 1888:1891 arg1 consistent 1863:1872 consistent 1863:1872 consistent 1863:1872 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 11 19 from lots 1888:1891 arg1 patterns 1849:1856 The glycosylation patterns 1831:1856 The glycosylation patterns 1831:1856 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 7 20 theme oligosaccharides 1246:1261 arg1 majority 1230:1237 the majority 1226:1237 the majority of the oligosaccharides (approximately 92%) 1226:1281 A total of eight acidic and 12 neutral structures were identified, and the majority of the oligosaccharides (approximately 92%) were found to be sialylated. 8969451 1 21 theme Factor 265:270 arg1 rFVIII 278:283 rFVIII 278:283 rFVIII 278:283 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 1 21 theme Factor 265:270 arg1 VIII 272:275 recombinant human Factor VIII 247:275 recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells 247:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 10 22 located found 1792:1796 arg2 structures 1706:1715 The Gal alpha 1-3Gal structures 1685:1715 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII 1685:1781 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 10 22 located found 1792:1796 arg1 protein 1822:1828 the CHO-cell-derived protein 1801:1828 the CHO-cell-derived protein 1801:1828 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 9 23 dep structures 1648:1657 arg1 each 1660:1663 each 1660:1663 each 1660:1663 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 10 24 theme alpha 1693:1697 arg1 structures 1706:1715 The Gal alpha 1-3Gal structures 1685:1715 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII 1685:1781 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 11 25 theme oligosaccharides 2046:2061 arg1 % 2019:2019 approximately 98% 2003:2019 approximately 98% of all asparagine-linked oligosaccharides 2003:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 11 25 theme oligosaccharides 2046:2061 arg1 oligosaccharides 2046:2061 all asparagine-linked oligosaccharides 2024:2061 all asparagine-linked oligosaccharides 2024:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 11 26 from consistent 1863:1872 arg1 lots 1888:1891 six random lots 1877:1891 six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides 1877:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 11 26 from consistent 1863:1872 arg1 [coefficient 1903:1914 rFVIII [coefficient 1896:1914 rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides 1896:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 2 27 dep large 333:337 arg1 kDa 344:346 300 kDa 340:346 300 kDa 340:346 FVIII, a large (300 kDa) glycoprotein, is employed therapeutically for the correction of haemophilia A. 8969451 1 28 theme moiety 178:183 arg1 measure 199:205 a critical measure 188:205 a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells 188:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 1 28 theme moiety 178:183 arg1 Characterization 141:156 Characterization 141:156 Characterization of the carbohydrate moiety 141:183 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 0 29 theme factor 72:77 arg1 VIII 79:82 recombinant human factor VIII 54:82 recombinant human factor VIII 54:82 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII using fluorophore-assisted carbohydrate electrophoresis. 8969451 5 30 theme FACE 999:1002 arg1 gels 1015:1018 FACE sequencing gels 999:1018 FACE sequencing gels 999:1018 The electrophoretically resolved oligosaccharide bands were isolated and individual bands subjected to digestion with defined pools of exoglycosidases and re-electrophoresed on FACE sequencing gels. 8969451 9 31 dep each 1660:1663 arg1 % 1681:1681 % 1681:1681 % 1681:1681 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 5 32 theme oligosaccharide 855:869 arg1 bands 871:875 The electrophoretically resolved oligosaccharide bands 822:875 The electrophoretically resolved oligosaccharide bands 822:875 The electrophoretically resolved oligosaccharide bands were isolated and individual bands subjected to digestion with defined pools of exoglycosidases and re-electrophoresed on FACE sequencing gels. 8969451 0 33 theme carbohydrate 111:122 arg1 electrophoresis 124:138 fluorophore-assisted carbohydrate electrophoresis 90:138 fluorophore-assisted carbohydrate electrophoresis 90:138 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII using fluorophore-assisted carbohydrate electrophoresis. 8969451 4 34 from rFVIII 595:600 arg1 oligosaccharides 573:588 The N-linked oligosaccharides 560:588 The N-linked oligosaccharides from rFVIII 560:600 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 0 35 theme VIII 79:82 arg1 structures 40:49 N-linked oligosaccharide structures 15:49 N-linked oligosaccharide structures of recombinant human factor VIII 15:82 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII using fluorophore-assisted carbohydrate electrophoresis. 8969451 11 36 theme bands 1982:1986 arg1 [coefficient 1903:1914 rFVIII [coefficient 1896:1914 rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides 1896:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 2 37 gly glycoprotein 349:360 arg1 FVIII 324:328 FVIII 324:328 FVIII 324:328 FVIII, a large (300 kDa) glycoprotein, is employed therapeutically for the correction of haemophilia A. 8969451 2 37 gly glycoprotein 349:360 arg1 glycoprotein 349:360 a large (300 kDa) glycoprotein 331:360 a large (300 kDa) glycoprotein 331:360 FVIII, a large (300 kDa) glycoprotein, is employed therapeutically for the correction of haemophilia A. 8969451 1 38 theme CHO 312:314 arg1 cells 317:321 Chinese-hamster ovary (CHO) cells 289:321 Chinese-hamster ovary (CHO) cells 289:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 7 39 theme neutral 1186:1192 arg1 structures 1194:1203 12 neutral structures 1183:1203 12 neutral structures 1183:1203 A total of eight acidic and 12 neutral structures were identified, and the majority of the oligosaccharides (approximately 92%) were found to be sialylated. 8969451 0 40 theme N-linked 15:22 arg1 structures 40:49 N-linked oligosaccharide structures 15:49 N-linked oligosaccharide structures of recombinant human factor VIII 15:82 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII using fluorophore-assisted carbohydrate electrophoresis. 8969451 11 41 link asparagine-linked 2028:2044 arg1 oligosaccharides 2046:2061 all asparagine-linked oligosaccharides 2024:2061 all asparagine-linked oligosaccharides 2024:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 5 42 with digestion 925:933 arg1 pools 948:952 defined pools 940:952 defined pools of exoglycosidases 940:971 The electrophoretically resolved oligosaccharide bands were isolated and individual bands subjected to digestion with defined pools of exoglycosidases and re-electrophoresed on FACE sequencing gels. 8969451 2 43 theme haemophilia 413:423 arg1 A 425:425 haemophilia A 413:425 haemophilia A 413:425 FVIII, a large (300 kDa) glycoprotein, is employed therapeutically for the correction of haemophilia A. 8969451 0 44 theme structures 40:49 arg1 Elucidation 0:10 Elucidation 0:10 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII 0:82 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII using fluorophore-assisted carbohydrate electrophoresis. 8969451 10 45 theme CHO-cell-derived 1805:1820 arg1 protein 1822:1828 the CHO-cell-derived protein 1801:1828 the CHO-cell-derived protein 1801:1828 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 0 46 theme recombinant 54:64 arg1 VIII 79:82 recombinant human factor VIII 54:82 recombinant human factor VIII 54:82 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII using fluorophore-assisted carbohydrate electrophoresis. 8969451 10 47 link baby-hamster-kidney-cell-derived 1743:1774 arg1 rFVIII 1776:1781 baby-hamster-kidney-cell-derived rFVIII 1743:1781 baby-hamster-kidney-cell-derived rFVIII 1743:1781 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 1 48 theme VIII 272:275 arg1 consistency 232:242 manufacturing process consistency 210:242 manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells 210:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 10 49 from rFVIII 1776:1781 arg1 present 1732:1738 present 1732:1738 present 1732:1738 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 8 50 from present 1419:1425 arg1 FVIII 1445:1449 plasma-derived FVIII 1430:1449 plasma-derived FVIII 1430:1449 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 6 51 theme gel 1035:1037 arg1 patterns 1039:1046 The resulting gel patterns 1021:1046 The resulting gel patterns 1021:1046 The resulting gel patterns were interpreted, based on band mobility shifts, to obtain the sequence structure of the oligosaccharides. 8969451 4 52 theme N-glycosidase 637:649 arg1 F 651:651 peptide N-glycosidase F 629:651 peptide N-glycosidase F 629:651 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 5 53 theme resolved 846:853 arg1 bands 871:875 The electrophoretically resolved oligosaccharide bands 822:875 The electrophoretically resolved oligosaccharide bands 822:875 The electrophoretically resolved oligosaccharide bands were isolated and individual bands subjected to digestion with defined pools of exoglycosidases and re-electrophoresed on FACE sequencing gels. 8969451 3 54 theme current 504:510 arg1 study 512:516 the current study 500:516 the current study 500:516 While N-linked and O-linked oligosaccharides are found in this protein, the current study focuses on the N-linked oligosaccharides. 8969451 4 55 link N-linked 564:571 arg1 oligosaccharides 573:588 The N-linked oligosaccharides 560:588 The N-linked oligosaccharides from rFVIII 560:600 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 1 56 theme ovary 305:309 arg1 cells 317:321 Chinese-hamster ovary (CHO) cells 289:321 Chinese-hamster ovary (CHO) cells 289:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 5 57 theme sequencing 1004:1013 arg1 gels 1015:1018 FACE sequencing gels 999:1018 FACE sequencing gels 999:1018 The electrophoretically resolved oligosaccharide bands were isolated and individual bands subjected to digestion with defined pools of exoglycosidases and re-electrophoresed on FACE sequencing gels. 8969451 1 58 from cells 317:321 arg1 consistency 232:242 manufacturing process consistency 210:242 manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells 210:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 8 59 theme major 1323:1327 arg1 structures 1345:1354 the major oligosaccharide structures 1319:1354 the major oligosaccharide structures found in CHO-cell-derived rFVIII 1319:1387 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 3 60 link N-linked 434:441 arg1 oligosaccharides 456:471 N-linked and O-linked oligosaccharides 434:471 N-linked and O-linked oligosaccharides 434:471 While N-linked and O-linked oligosaccharides are found in this protein, the current study focuses on the N-linked oligosaccharides. 8969451 10 61 theme Gal 1689:1691 arg1 structures 1706:1715 The Gal alpha 1-3Gal structures 1685:1715 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII 1685:1781 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 2 62 theme large 333:337 arg1 FVIII 324:328 FVIII 324:328 FVIII 324:328 FVIII, a large (300 kDa) glycoprotein, is employed therapeutically for the correction of haemophilia A. 8969451 2 62 theme large 333:337 arg1 glycoprotein 349:360 a large (300 kDa) glycoprotein 331:360 a large (300 kDa) glycoprotein 331:360 FVIII, a large (300 kDa) glycoprotein, is employed therapeutically for the correction of haemophilia A. 8969451 1 63 theme process 224:230 arg1 consistency 232:242 manufacturing process consistency 210:242 manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells 210:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 6 64 theme mobility 1080:1087 arg1 shifts 1089:1094 band mobility shifts 1075:1094 band mobility shifts 1075:1094 The resulting gel patterns were interpreted, based on band mobility shifts, to obtain the sequence structure of the oligosaccharides. 8969451 3 65 link O-linked 447:454 arg1 oligosaccharides 456:471 N-linked and O-linked oligosaccharides 434:471 N-linked and O-linked oligosaccharides 434:471 While N-linked and O-linked oligosaccharides are found in this protein, the current study focuses on the N-linked oligosaccharides. 8969451 11 66 theme variation 1919:1927 arg1 [coefficient 1903:1914 rFVIII [coefficient 1896:1914 rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides 1896:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 9 67 dep disialylated 1480:1491 arg1 followed 1545:1552 followed 1545:1552 followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%) 1545:1682 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 9 67 dep disialylated 1480:1491 arg1 core-fucosylated 1507:1522 core-fucosylated 1507:1522 core-fucosylated 1507:1522 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 9 67 dep disialylated 1480:1491 arg1 biantennary 1494:1504 biantennary 1494:1504 biantennary 1494:1504 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 8 68 theme oligosaccharide 1329:1343 arg1 structures 1345:1354 the major oligosaccharide structures 1319:1354 the major oligosaccharide structures found in CHO-cell-derived rFVIII 1319:1387 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 11 69 theme [coefficient 1903:1914 arg1 lots 1888:1891 six random lots 1877:1891 six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides 1877:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 11 69 theme [coefficient 1903:1914 arg1 [coefficient 1903:1914 rFVIII [coefficient 1896:1914 rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides 1896:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 5 70 theme defined 940:946 arg1 pools 948:952 defined pools 940:952 defined pools of exoglycosidases 940:971 The electrophoretically resolved oligosaccharide bands were isolated and individual bands subjected to digestion with defined pools of exoglycosidases and re-electrophoresed on FACE sequencing gels. 8969451 10 71 theme 1-3Gal 1699:1704 arg1 structures 1706:1715 The Gal alpha 1-3Gal structures 1685:1715 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII 1685:1781 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 8 72 link plasma-derived 1430:1443 arg1 FVIII 1445:1449 plasma-derived FVIII 1430:1449 plasma-derived FVIII 1430:1449 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 11 73 theme asparagine-linked 2028:2044 arg1 oligosaccharides 2046:2061 all asparagine-linked oligosaccharides 2024:2061 all asparagine-linked oligosaccharides 2024:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 9 74 dep core-fucosylated 1507:1522 arg1 % 1541:1541 approximately 40% 1525:1541 approximately 40% 1525:1541 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 11 75 theme glycosylation 1835:1847 arg1 consistent 1863:1872 consistent 1863:1872 consistent 1863:1872 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 11 75 theme glycosylation 1835:1847 arg1 patterns 1849:1856 The glycosylation patterns 1831:1856 The glycosylation patterns 1831:1856 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 8 76 theme CHO-cell-derived 1365:1380 arg1 rFVIII 1382:1387 CHO-cell-derived rFVIII 1365:1387 CHO-cell-derived rFVIII 1365:1387 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 1 77 from VIII 272:275 arg1 cells 317:321 Chinese-hamster ovary (CHO) cells 289:321 Chinese-hamster ovary (CHO) cells 289:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 1 78 theme carbohydrate 165:176 arg1 moiety 178:183 the carbohydrate moiety 161:183 the carbohydrate moiety 161:183 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 9 79 gly trisialylated 1557:1569 arg1 structures 1648:1657 trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures 1557:1657 trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%) 1557:1682 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 4 80 theme carbohydrate 785:796 arg1 FACE 815:818 FACE 815:818 FACE 815:818 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 4 80 theme carbohydrate 785:796 arg1 electrophoresis 798:812 fluorophore-assisted carbohydrate electrophoresis 764:812 fluorophore-assisted carbohydrate electrophoresis (FACE) 764:819 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 8 81 attach present 1419:1425 arg2 All 1312:1314 All 1312:1314 All 1312:1314 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 8 81 attach present 1419:1425 arg2 structures 1345:1354 the major oligosaccharide structures 1319:1354 the major oligosaccharide structures found in CHO-cell-derived rFVIII 1319:1387 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 8 81 attach present 1419:1425 arg1 FVIII 1445:1449 plasma-derived FVIII 1430:1449 plasma-derived FVIII 1430:1449 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 1 82 from consistency 232:242 arg1 cells 317:321 Chinese-hamster ovary (CHO) cells 289:321 Chinese-hamster ovary (CHO) cells 289:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 6 83 theme sequence 1111:1118 arg1 structure 1120:1128 the sequence structure 1107:1128 the sequence structure of the oligosaccharides 1107:1152 The resulting gel patterns were interpreted, based on band mobility shifts, to obtain the sequence structure of the oligosaccharides. 8969451 9 84 dep % 1681:1681 arg1 18 1679:1680 18 1679:1680 18 1679:1680 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 0 85 theme fluorophore-assisted 90:109 arg1 electrophoresis 124:138 fluorophore-assisted carbohydrate electrophoresis 90:138 fluorophore-assisted carbohydrate electrophoresis 90:138 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII using fluorophore-assisted carbohydrate electrophoresis. 8969451 1 86 theme critical 190:197 arg1 Characterization 141:156 Characterization 141:156 Characterization of the carbohydrate moiety 141:183 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 1 86 theme critical 190:197 arg1 measure 199:205 a critical measure 188:205 a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells 188:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 3 87 located found 477:481 arg1 protein 491:497 this protein 486:497 this protein 486:497 While N-linked and O-linked oligosaccharides are found in this protein, the current study focuses on the N-linked oligosaccharides. 8969451 3 87 located found 477:481 arg2 oligosaccharides 456:471 N-linked and O-linked oligosaccharides 434:471 N-linked and O-linked oligosaccharides 434:471 While N-linked and O-linked oligosaccharides are found in this protein, the current study focuses on the N-linked oligosaccharides. 8969451 3 88 link N-linked 533:540 arg1 oligosaccharides 542:557 the N-linked oligosaccharides 529:557 the N-linked oligosaccharides 529:557 While N-linked and O-linked oligosaccharides are found in this protein, the current study focuses on the N-linked oligosaccharides. 8969451 11 89 theme random 1881:1886 arg1 lots 1888:1891 six random lots 1877:1891 six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides 1877:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 11 89 theme random 1881:1886 arg1 [coefficient 1903:1914 rFVIII [coefficient 1896:1914 rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides 1896:2061 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 11 90 dep % 1930:1930 arg1 3-14 1933:1936 3-14 1933:1936 3-14 1933:1936 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 8 91 theme plasma-derived 1430:1443 arg1 FVIII 1445:1449 plasma-derived FVIII 1430:1449 plasma-derived FVIII 1430:1449 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 3 92 theme O-linked 447:454 arg1 oligosaccharides 456:471 N-linked and O-linked oligosaccharides 434:471 N-linked and O-linked oligosaccharides 434:471 While N-linked and O-linked oligosaccharides are found in this protein, the current study focuses on the N-linked oligosaccharides. 8969451 5 93 theme individual 895:904 arg1 bands 906:910 individual bands 895:910 individual bands 895:910 The electrophoretically resolved oligosaccharide bands were isolated and individual bands subjected to digestion with defined pools of exoglycosidases and re-electrophoresed on FACE sequencing gels. 8969451 8 94 located found 1356:1360 arg2 structures 1345:1354 the major oligosaccharide structures 1319:1354 the major oligosaccharide structures found in CHO-cell-derived rFVIII 1319:1387 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 8 94 located found 1356:1360 arg1 rFVIII 1382:1387 CHO-cell-derived rFVIII 1365:1387 CHO-cell-derived rFVIII 1365:1387 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 4 95 theme N-linked 564:571 arg1 oligosaccharides 573:588 The N-linked oligosaccharides 560:588 The N-linked oligosaccharides from rFVIII 560:600 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 7 96 gly sialylated 1300:1309 arg1 majority 1230:1237 the majority 1226:1237 the majority of the oligosaccharides (approximately 92%) 1226:1281 A total of eight acidic and 12 neutral structures were identified, and the majority of the oligosaccharides (approximately 92%) were found to be sialylated. 8969451 3 97 theme N-linked 434:441 arg1 oligosaccharides 456:471 N-linked and O-linked oligosaccharides 434:471 N-linked and O-linked oligosaccharides 434:471 While N-linked and O-linked oligosaccharides are found in this protein, the current study focuses on the N-linked oligosaccharides. 8969451 0 98 theme oligosaccharide 24:38 arg1 structures 40:49 N-linked oligosaccharide structures 15:49 N-linked oligosaccharide structures of recombinant human factor VIII 15:82 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII using fluorophore-assisted carbohydrate electrophoresis. 8969451 2 99 theme A 425:425 arg1 correction 399:408 the correction 395:408 the correction of haemophilia A 395:425 FVIII, a large (300 kDa) glycoprotein, is employed therapeutically for the correction of haemophilia A. 8969451 1 100 theme human 259:263 arg1 rFVIII 278:283 rFVIII 278:283 rFVIII 278:283 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 1 100 theme human 259:263 arg1 VIII 272:275 recombinant human Factor VIII 247:275 recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells 247:321 Characterization of the carbohydrate moiety is a critical measure of manufacturing process consistency of recombinant human Factor VIII (rFVIII) in Chinese-hamster ovary (CHO) cells. 8969451 6 101 theme oligosaccharides 1137:1152 arg1 structure 1120:1128 the sequence structure 1107:1128 the sequence structure of the oligosaccharides 1107:1152 The resulting gel patterns were interpreted, based on band mobility shifts, to obtain the sequence structure of the oligosaccharides. 8969451 10 102 theme baby-hamster-kidney-cell-derived 1743:1774 arg1 rFVIII 1776:1781 baby-hamster-kidney-cell-derived rFVIII 1743:1781 baby-hamster-kidney-cell-derived rFVIII 1743:1781 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 0 103 theme human 66:70 arg1 VIII 79:82 recombinant human factor VIII 54:82 recombinant human factor VIII 54:82 Elucidation of N-linked oligosaccharide structures of recombinant human factor VIII using fluorophore-assisted carbohydrate electrophoresis. 8969451 11 104 theme percentage 1948:1957 arg1 data 1974:1977 percentage lane luminance data 1948:1977 percentage lane luminance data 1948:1977 The glycosylation patterns were consistent in six random lots of rFVIII [coefficient of variation (%) 3-14] based on percentage lane luminance data of bands that represent approximately 98% of all asparagine-linked oligosaccharides. 8969451 8 105 from FVIII 1445:1449 arg1 present 1419:1425 present 1419:1425 present 1419:1425 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 10 106 from present 1732:1738 arg1 rFVIII 1776:1781 baby-hamster-kidney-cell-derived rFVIII 1743:1781 baby-hamster-kidney-cell-derived rFVIII 1743:1781 The Gal alpha 1-3Gal structures reported to be present in baby-hamster-kidney-cell-derived rFVIII were not found in the CHO-cell-derived protein. 8969451 4 107 theme peptide 629:635 arg1 F 651:651 peptide N-glycosidase F 629:651 peptide N-glycosidase F 629:651 The N-linked oligosaccharides from rFVIII were released using either peptide N-glycosidase F or endoglycosidase H, derivatized with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonate, and analysed by fluorophore-assisted carbohydrate electrophoresis (FACE). 8969451 9 108 dep trisialylated 1557:1569 arg1 core-fucosylated 1631:1646 core-fucosylated 1631:1646 core-fucosylated 1631:1646 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 9 108 dep trisialylated 1557:1569 arg1 monosialo 1607:1615 monosialo 1607:1615 monosialo 1607:1615 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 9 108 dep trisialylated 1557:1569 arg1 core-fucosylated 1586:1601 core-fucosylated 1586:1601 core-fucosylated 1586:1601 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 9 108 dep trisialylated 1557:1569 arg1 triantennary 1572:1583 triantennary 1572:1583 triantennary 1572:1583 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 9 108 dep trisialylated 1557:1569 arg1 biantennary 1618:1628 biantennary 1618:1628 biantennary 1618:1628 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 8969451 8 109 located present 1419:1425 arg2 All 1312:1314 All 1312:1314 All 1312:1314 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 8 109 located present 1419:1425 arg2 structures 1345:1354 the major oligosaccharide structures 1319:1354 the major oligosaccharide structures found in CHO-cell-derived rFVIII 1319:1387 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 8 109 located present 1419:1425 arg1 FVIII 1445:1449 plasma-derived FVIII 1430:1449 plasma-derived FVIII 1430:1449 All of the major oligosaccharide structures found in CHO-cell-derived rFVIII have also been reported to be present in plasma-derived FVIII. 8969451 9 110 theme trisialylated 1557:1569 arg1 structures 1648:1657 trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures 1557:1657 trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%) 1557:1682 Among the most abundant are disialylated, biantennary, core-fucosylated (approximately 40%), followed by trisialylated, triantennary, core-fucosylated and monosialo, biantennary, core-fucosylated structures (each approximately 18%). 1175622 0 0 theme patient 96:102 arg1 urine 85:89 the urine 81:89 the urine of a patient with sialuria 81:116 Isolation and identification of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid from the urine of a patient with sialuria. 1175622 4 1 theme acid/thiobarbituric 546:564 arg1 tests 571:575 the periodic acid/thiobarbituric acid tests 533:575 the periodic acid/thiobarbituric acid tests 533:575 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 1 2 with patient 176:182 arg1 sialuria 189:196 sialuria 189:196 sialuria 189:196 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 0 3 with patient 96:102 arg1 sialuria 109:116 sialuria 109:116 sialuria 109:116 Isolation and identification of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid from the urine of a patient with sialuria. 1175622 1 4 theme patient 176:182 arg1 urine 165:169 the urine 161:169 the urine of a patient with sialuria 161:196 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 1 5 from urine 165:169 arg1 preparations 143:154 N-Acetylneuraminic acid preparations 119:154 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria 119:196 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 3 6 theme mass 383:386 arg1 spectrometry 388:399 mass spectrometry 383:399 mass spectrometry 383:399 The structure has been elucidated by mass spectrometry and confirmed by comparison with the synthetic compound. 1175622 5 7 theme acylneuraminate 670:684 arg1 pyruvatelyase 686:698 acylneuraminate pyruvatelyase 670:698 acylneuraminate pyruvatelyase 670:698 It does not react with acylneuraminate pyruvatelyase. 1175622 4 8 theme periodic 537:544 arg1 tests 571:575 the periodic acid/thiobarbituric acid tests 533:575 the periodic acid/thiobarbituric acid tests 533:575 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 4 9 from chromatography 617:630 arg1 properties 462:471 The properties 458:471 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography 458:630 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 4 10 theme gas-liquid 606:615 arg1 chromatography 617:630 thin-layer and gas-liquid chromatography 591:630 chromatography 617:630 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 4 11 from orcinol/Fe3+/HCl 512:527 arg1 properties 462:471 The properties 458:471 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography 458:630 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 3 12 with comparison 418:427 arg1 compound 448:455 the synthetic compound 434:455 the synthetic compound 434:455 The structure has been elucidated by mass spectrometry and confirmed by comparison with the synthetic compound. 1175622 1 13 theme 1--2 206:209 arg1 % 210:210 1--2% 206:210 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 206:257 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 1 13 theme 1--2 206:209 arg1 acid 254:257 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 215:257 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 215:257 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 4 14 theme acid 500:503 arg1 properties 462:471 The properties 458:471 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography 458:630 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 1 15 theme N-Acetylneuraminic 119:136 arg1 preparations 143:154 N-Acetylneuraminic acid preparations 119:154 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria 119:196 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 6 16 theme acid 737:740 arg1 origin 705:710 The origin 701:710 The origin of this new human sialic acid 701:740 The origin of this new human sialic acid is discussed. 1175622 0 17 theme acid 71:74 arg1 identification 14:27 identification 14:27 identification 14:27 Isolation and identification of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid from the urine of a patient with sialuria. 1175622 0 17 theme acid 71:74 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and identification of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid from the urine of a patient with sialuria. 1175622 4 18 from acid 500:503 arg1 orcinol/Fe3+/HCl 512:527 the orcinol/Fe3+/HCl 508:527 the orcinol/Fe3+/HCl 508:527 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 4 18 from acid 500:503 arg1 chromatography 617:630 thin-layer and gas-liquid chromatography 591:630 chromatography 617:630 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 1 19 contain contain 198:204 arg2 acid 254:257 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 215:257 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 215:257 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 1 19 contain contain 198:204 arg1 preparations 143:154 N-Acetylneuraminic acid preparations 119:154 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria 119:196 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 1 19 contain contain 198:204 arg2 % 210:210 1--2% 206:210 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 206:257 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 2 20 theme human 269:273 arg1 acid 282:285 This new human sialic acid 260:285 This new human sialic acid 260:285 This new human sialic acid was isolated by ion-exchange and partition chromatography. 1175622 6 21 theme sialic 730:735 arg1 acid 737:740 this new human sialic acid 715:740 this new human sialic acid 715:740 The origin of this new human sialic acid is discussed. 1175622 1 22 theme 2-deoxy-2,3-dehydro-N-acetylneuraminic 215:252 arg1 acid 254:257 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 215:257 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 215:257 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 0 23 theme 2-deoxy-2,3-dehydro-N-acetylneuraminic 32:69 arg1 acid 71:74 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 32:74 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 32:74 Isolation and identification of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid from the urine of a patient with sialuria. 1175622 2 24 theme new 265:267 arg1 acid 282:285 This new human sialic acid 260:285 This new human sialic acid 260:285 This new human sialic acid was isolated by ion-exchange and partition chromatography. 1175622 1 25 theme acid 254:257 arg1 % 210:210 1--2% 206:210 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 206:257 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 1 25 theme acid 254:257 arg1 acid 254:257 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 215:257 2-deoxy-2,3-dehydro-N-acetylneuraminic acid 215:257 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 3 26 theme synthetic 438:446 arg1 compound 448:455 the synthetic compound 434:455 the synthetic compound 434:455 The structure has been elucidated by mass spectrometry and confirmed by comparison with the synthetic compound. 1175622 0 27 from urine 85:89 arg1 identification 14:27 identification 14:27 identification 14:27 Isolation and identification of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid from the urine of a patient with sialuria. 1175622 0 27 from urine 85:89 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and identification of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid from the urine of a patient with sialuria. 1175622 1 28 theme acid 138:141 arg1 preparations 143:154 N-Acetylneuraminic acid preparations 119:154 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria 119:196 N-Acetylneuraminic acid preparations from the urine of a patient with sialuria contain 1--2% of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. 1175622 4 29 theme thin-layer 591:600 arg1 chromatography 617:630 thin-layer and gas-liquid chromatography 591:630 chromatography 617:630 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 6 30 theme human 724:728 arg1 acid 737:740 this new human sialic acid 715:740 this new human sialic acid 715:740 The origin of this new human sialic acid is discussed. 1175622 4 31 theme sialic 493:498 arg1 acid 500:503 this unsaturated sialic acid 476:503 this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography 476:630 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 6 32 theme new 720:722 arg1 acid 737:740 this new human sialic acid 715:740 this new human sialic acid 715:740 The origin of this new human sialic acid is discussed. 1175622 4 33 from properties 462:471 arg1 orcinol/Fe3+/HCl 512:527 the orcinol/Fe3+/HCl 508:527 the orcinol/Fe3+/HCl 508:527 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 4 33 from properties 462:471 arg1 chromatography 617:630 thin-layer and gas-liquid chromatography 591:630 chromatography 617:630 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 4 34 theme unsaturated 481:491 arg1 acid 500:503 this unsaturated sialic acid 476:503 this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography 476:630 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 2 35 dep ion-exchange 303:314 arg1 chromatography 330:343 chromatography 330:343 chromatography 330:343 This new human sialic acid was isolated by ion-exchange and partition chromatography. 1175622 4 36 theme acid 566:569 arg1 tests 571:575 the periodic acid/thiobarbituric acid tests 533:575 the periodic acid/thiobarbituric acid tests 533:575 The properties of this unsaturated sialic acid in the orcinol/Fe3+/HCl and the periodic acid/thiobarbituric acid tests as well as in thin-layer and gas-liquid chromatography are described. 1175622 2 37 theme sialic 275:280 arg1 acid 282:285 This new human sialic acid 260:285 This new human sialic acid 260:285 This new human sialic acid was isolated by ion-exchange and partition chromatography. 1473102 6 0 theme sulfated 1564:1571 arg1 sialyl-oligosaccharides 1573:1595 linear unbranched sulfated sialyl-oligosaccharides 1546:1595 linear unbranched sulfated sialyl-oligosaccharides 1546:1595 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 1 1 theme P-2 504:506 arg1 chromatography 523:536 Bio-Gel P-2 size-exclusion chromatography 496:536 Bio-Gel P-2 size-exclusion chromatography 496:536 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 2 2 theme periodate 742:750 arg1 oxidation 752:760 periodate oxidation 742:760 periodate oxidation 742:760 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 2 3 theme fast-atom-bombardment 871:891 arg1 spectrometry 898:909 positive-ion fast-atom-bombardment mass spectrometry 858:909 positive-ion fast-atom-bombardment mass spectrometry (FABMS) 858:917 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 2 3 theme fast-atom-bombardment 871:891 arg1 FABMS 912:916 FABMS 912:916 FABMS 912:916 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 1 4 theme sialic 205:210 arg1 residue 217:223 a sialic acid residue 203:223 a sialic acid residue 203:223 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 4 5 theme 2-->6 1233:1237 arg1 -alpha 1239:1244 (2-->3)-alpha or (2-->6)-alpha 1215:1244 (2-->3)-alpha or (2-->6)-alpha 1215:1244 The sialic acid residues were found to be either bound (2-->6)-alpha to 2-acetamido-2-deoxy-D-galactitol or (2-->3)-alpha or (2-->6)-alpha to a D-galactose residue occupying a nonreducing terminus. 1473102 1 6 theme lectin 415:420 arg1 chromatography 431:444 immobilized Limulus polyphemus lectin affinity chromatography 384:444 immobilized Limulus polyphemus lectin affinity chromatography 384:444 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 2 7 theme Proposed 610:617 arg1 structures 619:628 Proposed structures 610:628 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides 610:688 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 1 8 attach isolated 231:238 arg2 each 162:165 each 162:165 each 162:165 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 8 attach isolated 231:238 arg1 glycoproteins 269:281 tracheobronchial mucous glycoproteins 245:281 tracheobronchial mucous glycoproteins 245:281 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 8 attach isolated 231:238 arg2 oligosaccharides 144:159 Thirteen novel oligosaccharides 129:159 Thirteen novel oligosaccharides 129:159 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 8 attach isolated 231:238 arg1 patient 290:296 a patient 288:296 a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC) 288:607 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 2 9 theme sulfated 657:664 arg1 sialyl-oligosaccharides 666:688 the resulting purified sulfated sialyl-oligosaccharides 634:688 the resulting purified sulfated sialyl-oligosaccharides 634:688 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 2 10 theme products 832:839 arg1 analyses 732:739 carbohydrate/permethylation analyses 704:739 carbohydrate/permethylation analyses 704:739 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 2 10 theme products 832:839 arg1 oxidation 752:760 periodate oxidation 742:760 periodate oxidation 742:760 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 2 10 theme products 832:839 arg1 analysis 809:816 analysis 809:816 analysis of desulfated products 809:839 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 2 10 theme products 832:839 arg1 digestion 798:806 complete sequential exoglycosidase digestion 763:806 complete sequential exoglycosidase digestion 763:806 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 2 10 theme products 832:839 arg1 analysis 846:853 analysis 846:853 analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS) 846:917 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 1 11 theme SynChroprep 447:457 arg1 chromatography 480:493 SynChroprep AX300 anion-exchange chromatography 447:493 SynChroprep AX300 anion-exchange chromatography 447:493 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 2 12 theme resulting 638:646 arg1 sialyl-oligosaccharides 666:688 the resulting purified sulfated sialyl-oligosaccharides 634:688 the resulting purified sulfated sialyl-oligosaccharides 634:688 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 1 13 theme anion-exchange 465:478 arg1 chromatography 480:493 SynChroprep AX300 anion-exchange chromatography 447:493 SynChroprep AX300 anion-exchange chromatography 447:493 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 7 14 theme sulfate 1861:1867 arg1 ester 1869:1873 a sulfate ester 1859:1873 a sulfate ester 1859:1873 These results demonstrate that it is possible for sialic acid and a sulfate ester to exist on the same oligosaccharide and that this oligosaccharide can be as small as a trisaccharide. 1473102 1 15 theme sulfate 185:191 arg1 ester 193:197 a sulfate ester 183:197 a sulfate ester 183:197 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 7 16 theme sialic 1843:1848 arg1 acid 1850:1853 sialic acid 1843:1853 sialic acid 1843:1853 These results demonstrate that it is possible for sialic acid and a sulfate ester to exist on the same oligosaccharide and that this oligosaccharide can be as small as a trisaccharide. 1473102 2 17 theme complete 763:770 arg1 digestion 798:806 complete sequential exoglycosidase digestion 763:806 complete sequential exoglycosidase digestion 763:806 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 0 18 theme cystic 112:117 arg1 fibrosis 119:126 cystic fibrosis 112:126 cystic fibrosis 112:126 Sulfated sialyl-oligosaccharides derived from tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis. 1473102 6 19 theme 2-acetamido-2-deoxy-D-glucose 1754:1782 arg1 residue 1784:1790 a 2-acetamido-2-deoxy-D-glucose residue 1752:1790 a 2-acetamido-2-deoxy-D-glucose residue 1752:1790 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 3 20 theme C-4 1068:1070 arg1 C-6 979:981 C-6 979:981 C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue 979:1104 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 4 21 theme acid 1118:1121 arg1 residues 1123:1130 The sialic acid residues 1107:1130 The sialic acid residues 1107:1130 The sialic acid residues were found to be either bound (2-->6)-alpha to 2-acetamido-2-deoxy-D-galactitol or (2-->3)-alpha or (2-->6)-alpha to a D-galactose residue occupying a nonreducing terminus. 1473102 5 22 theme sulfate 1443:1449 arg1 ester 1451:1455 a sulfate ester 1441:1455 a sulfate ester 1441:1455 For this group of oligosaccharides, ranging in size from tri- to hepta-saccharides, it was also observed that a sialic acid residue and a sulfate ester did not residue on the same oligosaccharide branch when more than one branch existed. 1473102 1 23 theme Limulus 396:402 arg1 polyphemus 404:413 immobilized Limulus polyphemus 384:413 immobilized Limulus polyphemus lectin affinity chromatography 384:444 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 3 24 theme residue 1057:1063 arg1 C-6 979:981 C-6 979:981 C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue 979:1104 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 0 25 theme Sulfated 0:7 arg1 sialyl-oligosaccharides 9:31 Sulfated sialyl-oligosaccharides 0:31 Sulfated sialyl-oligosaccharides 0:31 Sulfated sialyl-oligosaccharides derived from tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis. 1473102 6 26 theme internal 1728:1735 arg1 D-galactose 1737:1747 an internal D-galactose 1725:1747 an internal D-galactose 1725:1747 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 3 27 theme D-galactose 1086:1096 arg1 residue 1098:1104 a terminal D-galactose residue 1075:1104 a terminal D-galactose residue 1075:1104 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 2 28 theme exoglycosidase 783:796 arg1 digestion 798:806 complete sequential exoglycosidase digestion 763:806 complete sequential exoglycosidase digestion 763:806 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 5 29 theme acid 1424:1427 arg1 residue 1429:1435 a sialic acid residue 1415:1435 a sialic acid residue 1415:1435 For this group of oligosaccharides, ranging in size from tri- to hepta-saccharides, it was also observed that a sialic acid residue and a sulfate ester did not residue on the same oligosaccharide branch when more than one branch existed. 1473102 0 30 theme tracheobronchial 46:61 arg1 glycoproteins 70:82 tracheobronchial mucous glycoproteins 46:82 tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis 46:126 Sulfated sialyl-oligosaccharides derived from tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis. 1473102 3 31 from esters 928:933 arg1 sialyl-oligosaccharides 944:966 these sialyl-oligosaccharides 938:966 these sialyl-oligosaccharides 938:966 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 5 32 theme oligosaccharide 1485:1499 arg1 branch 1501:1506 the same oligosaccharide branch 1476:1506 the same oligosaccharide branch 1476:1506 For this group of oligosaccharides, ranging in size from tri- to hepta-saccharides, it was also observed that a sialic acid residue and a sulfate ester did not residue on the same oligosaccharide branch when more than one branch existed. 1473102 1 33 theme alkaline 335:342 arg1 borohydride 344:354 alkaline borohydride 335:354 alkaline borohydride treatment 335:364 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 4 34 theme -alpha 1222:1227 arg1 -alpha 1239:1244 (2-->3)-alpha or (2-->6)-alpha 1215:1244 (2-->3)-alpha or (2-->6)-alpha 1215:1244 The sialic acid residues were found to be either bound (2-->6)-alpha to 2-acetamido-2-deoxy-D-galactitol or (2-->3)-alpha or (2-->6)-alpha to a D-galactose residue occupying a nonreducing terminus. 1473102 1 35 theme liquid 580:585 arg1 HPLC 603:606 HPLC 603:606 HPLC 603:606 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 35 theme liquid 580:585 arg1 chromatography 587:600 Hypersil 120A APS-2 high-performance liquid chromatography 543:600 Hypersil 120A APS-2 high-performance liquid chromatography (HPLC) 543:607 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 6 36 theme acid 1609:1612 arg1 residue 1614:1620 the sialic acid residue 1598:1620 the sialic acid residue 1598:1620 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 5 37 theme same 1480:1483 arg1 branch 1501:1506 the same oligosaccharide branch 1476:1506 the same oligosaccharide branch 1476:1506 For this group of oligosaccharides, ranging in size from tri- to hepta-saccharides, it was also observed that a sialic acid residue and a sulfate ester did not residue on the same oligosaccharide branch when more than one branch existed. 1473102 4 38 theme nonreducing 1283:1293 arg1 terminus 1295:1302 a nonreducing terminus 1281:1302 a nonreducing terminus 1281:1302 The sialic acid residues were found to be either bound (2-->6)-alpha to 2-acetamido-2-deoxy-D-galactitol or (2-->3)-alpha or (2-->6)-alpha to a D-galactose residue occupying a nonreducing terminus. 1473102 1 39 theme tracheobronchial 245:260 arg1 glycoproteins 269:281 tracheobronchial mucous glycoproteins 245:281 tracheobronchial mucous glycoproteins 245:281 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 5 40 theme oligosaccharides 1323:1338 arg1 oligosaccharides 1323:1338 oligosaccharides 1323:1338 oligosaccharides 1323:1338 For this group of oligosaccharides, ranging in size from tri- to hepta-saccharides, it was also observed that a sialic acid residue and a sulfate ester did not residue on the same oligosaccharide branch when more than one branch existed. 1473102 5 40 theme oligosaccharides 1323:1338 arg1 group 1314:1318 this group 1309:1318 this group of oligosaccharides, ranging in size from tri- to hepta-saccharides 1309:1386 For this group of oligosaccharides, ranging in size from tri- to hepta-saccharides, it was also observed that a sialic acid residue and a sulfate ester did not residue on the same oligosaccharide branch when more than one branch existed. 1473102 1 41 theme Bio-Gel 496:502 arg1 chromatography 523:536 Bio-Gel P-2 size-exclusion chromatography 496:536 Bio-Gel P-2 size-exclusion chromatography 496:536 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 6 42 theme unbranched 1553:1562 arg1 sialyl-oligosaccharides 1573:1595 linear unbranched sulfated sialyl-oligosaccharides 1546:1595 linear unbranched sulfated sialyl-oligosaccharides 1546:1595 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 1 43 theme APS-2 557:561 arg1 HPLC 603:606 HPLC 603:606 HPLC 603:606 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 43 theme APS-2 557:561 arg1 chromatography 587:600 Hypersil 120A APS-2 high-performance liquid chromatography 543:600 Hypersil 120A APS-2 high-performance liquid chromatography (HPLC) 543:607 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 4 44 theme D-galactose 1251:1261 arg1 residue 1263:1269 a D-galactose residue 1249:1269 a D-galactose residue occupying a nonreducing terminus 1249:1302 The sialic acid residues were found to be either bound (2-->6)-alpha to 2-acetamido-2-deoxy-D-galactitol or (2-->3)-alpha or (2-->6)-alpha to a D-galactose residue occupying a nonreducing terminus. 1473102 1 45 theme size-exclusion 508:521 arg1 chromatography 523:536 Bio-Gel P-2 size-exclusion chromatography 496:536 Bio-Gel P-2 size-exclusion chromatography 496:536 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 7 46 theme same 1891:1894 arg1 oligosaccharide 1896:1910 the same oligosaccharide 1887:1910 the same oligosaccharide 1887:1910 These results demonstrate that it is possible for sialic acid and a sulfate ester to exist on the same oligosaccharide and that this oligosaccharide can be as small as a trisaccharide. 1473102 2 47 theme mass 893:896 arg1 spectrometry 898:909 positive-ion fast-atom-bombardment mass spectrometry 858:909 positive-ion fast-atom-bombardment mass spectrometry (FABMS) 858:917 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 2 47 theme mass 893:896 arg1 FABMS 912:916 FABMS 912:916 FABMS 912:916 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 1 48 contain possessing 167:176 arg2 ester 193:197 a sulfate ester 183:197 a sulfate ester 183:197 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 48 contain possessing 167:176 arg2 residue 217:223 a sialic acid residue 203:223 a sialic acid residue 203:223 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 48 contain possessing 167:176 arg1 each 162:165 each 162:165 each 162:165 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 48 contain possessing 167:176 arg1 oligosaccharides 144:159 Thirteen novel oligosaccharides 129:159 Thirteen novel oligosaccharides 129:159 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 6 49 theme D-galactose 1637:1647 arg1 residue 1649:1655 a D-galactose residue 1635:1655 a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose 1635:1747 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 2 50 theme carbohydrate/permethylation 704:730 arg1 analyses 732:739 carbohydrate/permethylation analyses 704:739 carbohydrate/permethylation analyses 704:739 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 1 51 theme Hypersil 543:550 arg1 HPLC 603:606 HPLC 603:606 HPLC 603:606 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 51 theme Hypersil 543:550 arg1 chromatography 587:600 Hypersil 120A APS-2 high-performance liquid chromatography 543:600 Hypersil 120A APS-2 high-performance liquid chromatography (HPLC) 543:607 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 52 theme acid 212:215 arg1 residue 217:223 a sialic acid residue 203:223 a sialic acid residue 203:223 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 3 53 theme internal 1003:1010 arg1 D-galactose 1012:1022 an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue 1000:1063 D-galactose 1012:1022 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 3 54 theme Sulfate 920:926 arg1 esters 928:933 Sulfate esters 920:933 Sulfate esters on these sialyl-oligosaccharides 920:966 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 1 55 theme novel 138:142 arg1 each 162:165 each 162:165 each 162:165 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 55 theme novel 138:142 arg1 oligosaccharides 144:159 Thirteen novel oligosaccharides 129:159 Thirteen novel oligosaccharides 129:159 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 2 56 theme purified 648:655 arg1 sialyl-oligosaccharides 666:688 the resulting purified sulfated sialyl-oligosaccharides 634:688 the resulting purified sulfated sialyl-oligosaccharides 634:688 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 2 57 theme desulfated 821:830 arg1 products 832:839 desulfated products 821:839 desulfated products 821:839 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 1 58 theme AX300 459:463 arg1 chromatography 480:493 SynChroprep AX300 anion-exchange chromatography 447:493 SynChroprep AX300 anion-exchange chromatography 447:493 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 6 59 theme sulfate 1699:1705 arg1 ester 1707:1711 the sulfate ester 1695:1711 the sulfate ester residing on an internal D-galactose 1695:1747 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 2 60 theme positive-ion 858:869 arg1 spectrometry 898:909 positive-ion fast-atom-bombardment mass spectrometry 858:909 positive-ion fast-atom-bombardment mass spectrometry (FABMS) 858:917 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 2 60 theme positive-ion 858:869 arg1 FABMS 912:916 FABMS 912:916 FABMS 912:916 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 0 61 theme patient 89:95 arg1 glycoproteins 70:82 tracheobronchial mucous glycoproteins 46:82 tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis 46:126 Sulfated sialyl-oligosaccharides derived from tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis. 1473102 3 62 theme terminal 988:995 arg1 D-galactose 1012:1022 an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue 1000:1063 D-galactose 1012:1022 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 6 63 theme nonreducing 1669:1679 arg1 terminus 1681:1688 a nonreducing terminus 1667:1688 a nonreducing terminus with the sulfate ester residing on an internal D-galactose 1667:1747 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 3 64 theme 2-acetamido-2-deoxy-D-glucose 1027:1055 arg1 residue 1057:1063 an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue 1000:1063 residue 1057:1063 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 3 64 theme 2-acetamido-2-deoxy-D-glucose 1027:1055 arg1 residue 1098:1104 a terminal D-galactose residue 1075:1104 a terminal D-galactose residue 1075:1104 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 2 65 theme sequential 772:781 arg1 digestion 798:806 complete sequential exoglycosidase digestion 763:806 complete sequential exoglycosidase digestion 763:806 Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). 1473102 6 66 with terminus 1681:1688 arg1 ester 1707:1711 the sulfate ester 1695:1711 the sulfate ester residing on an internal D-galactose 1695:1747 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 3 67 theme D-galactose 1012:1022 arg1 C-6 979:981 C-6 979:981 C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue 979:1104 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 1 68 theme immobilized 384:394 arg1 polyphemus 404:413 immobilized Limulus polyphemus 384:413 immobilized Limulus polyphemus lectin affinity chromatography 384:444 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 4 69 theme sialic 1111:1116 arg1 residues 1123:1130 The sialic acid residues 1107:1130 The sialic acid residues 1107:1130 The sialic acid residues were found to be either bound (2-->6)-alpha to 2-acetamido-2-deoxy-D-galactitol or (2-->3)-alpha or (2-->6)-alpha to a D-galactose residue occupying a nonreducing terminus. 1473102 6 70 theme linear 1546:1551 arg1 sialyl-oligosaccharides 1573:1595 linear unbranched sulfated sialyl-oligosaccharides 1546:1595 linear unbranched sulfated sialyl-oligosaccharides 1546:1595 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 1 71 theme polyphemus 404:413 arg1 chromatography 431:444 immobilized Limulus polyphemus lectin affinity chromatography 384:444 immobilized Limulus polyphemus lectin affinity chromatography 384:444 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 72 gly glycoproteins 269:281 arg1 glycoproteins 269:281 tracheobronchial mucous glycoproteins 245:281 tracheobronchial mucous glycoproteins 245:281 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 4 73 theme 2-->6 1163:1167 arg1 -alpha 1169:1174 (2-->6)-alpha 1162:1174 (2-->6)-alpha to 2-acetamido-2-deoxy-D-galactitol or (2-->3)-alpha or (2-->6)-alpha 1162:1244 The sialic acid residues were found to be either bound (2-->6)-alpha to 2-acetamido-2-deoxy-D-galactitol or (2-->3)-alpha or (2-->6)-alpha to a D-galactose residue occupying a nonreducing terminus. 1473102 5 74 theme sialic 1417:1422 arg1 residue 1429:1435 a sialic acid residue 1415:1435 a sialic acid residue 1415:1435 For this group of oligosaccharides, ranging in size from tri- to hepta-saccharides, it was also observed that a sialic acid residue and a sulfate ester did not residue on the same oligosaccharide branch when more than one branch existed. 1473102 1 75 theme affinity 422:429 arg1 chromatography 431:444 immobilized Limulus polyphemus lectin affinity chromatography 384:444 immobilized Limulus polyphemus lectin affinity chromatography 384:444 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 76 theme cystic 303:308 arg1 fibrosis 310:317 cystic fibrosis 303:317 cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC) 303:607 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 3 77 theme residue 1098:1104 arg1 C-4 1068:1070 C-4 1068:1070 C-4 1068:1070 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 3 77 theme residue 1098:1104 arg1 D-galactose 1012:1022 an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue 1000:1063 D-galactose 1012:1022 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 3 77 theme residue 1098:1104 arg1 residue 1057:1063 an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue 1000:1063 residue 1057:1063 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 3 77 theme residue 1098:1104 arg1 residue 1098:1104 a terminal D-galactose residue 1075:1104 a terminal D-galactose residue 1075:1104 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 0 78 theme mucous 63:68 arg1 glycoproteins 70:82 tracheobronchial mucous glycoproteins 46:82 tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis 46:126 Sulfated sialyl-oligosaccharides derived from tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis. 1473102 3 79 theme terminal 1077:1084 arg1 residue 1098:1104 a terminal D-galactose residue 1075:1104 a terminal D-galactose residue 1075:1104 Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. 1473102 1 80 theme 120A 552:555 arg1 HPLC 603:606 HPLC 603:606 HPLC 603:606 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 80 theme 120A 552:555 arg1 chromatography 587:600 Hypersil 120A APS-2 high-performance liquid chromatography 543:600 Hypersil 120A APS-2 high-performance liquid chromatography (HPLC) 543:607 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 81 with patient 290:296 arg1 fibrosis 310:317 cystic fibrosis 303:317 cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC) 303:607 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 82 theme high-performance 563:578 arg1 HPLC 603:606 HPLC 603:606 HPLC 603:606 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 82 theme high-performance 563:578 arg1 chromatography 587:600 Hypersil 120A APS-2 high-performance liquid chromatography 543:600 Hypersil 120A APS-2 high-performance liquid chromatography (HPLC) 543:607 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 1 83 theme borohydride 344:354 arg1 treatment 356:364 alkaline borohydride treatment 335:364 alkaline borohydride treatment 335:364 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1473102 6 84 theme sialic 1602:1607 arg1 residue 1614:1620 the sialic acid residue 1598:1620 the sialic acid residue 1598:1620 On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. 1473102 0 85 gly glycoproteins 70:82 arg1 glycoproteins 70:82 tracheobronchial mucous glycoproteins 46:82 tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis 46:126 Sulfated sialyl-oligosaccharides derived from tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis. 1473102 4 86 theme or 1229:1230 arg1 -alpha 1239:1244 (2-->3)-alpha or (2-->6)-alpha 1215:1244 (2-->3)-alpha or (2-->6)-alpha 1215:1244 The sialic acid residues were found to be either bound (2-->6)-alpha to 2-acetamido-2-deoxy-D-galactitol or (2-->3)-alpha or (2-->6)-alpha to a D-galactose residue occupying a nonreducing terminus. 1473102 1 87 theme mucous 262:267 arg1 glycoproteins 269:281 tracheobronchial mucous glycoproteins 245:281 tracheobronchial mucous glycoproteins 245:281 Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). 1694115 7 0 theme single 1120:1125 arg1 oligosaccharide 1179:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 7 1 contain contains 1109:1116 arg2 oligosaccharide 1179:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 7 1 contain contains 1109:1116 arg1 product 1101:1107 our product 1097:1107 our product 1097:1107 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 0 2 theme cell 83:86 arg1 line 88:91 human hepatoma cell line 68:91 human hepatoma cell line 68:91 Unique structure of glycopeptide from alpha-fetoprotein produced in human hepatoma cell line, as determined by 1H-nuclear magnetic resonance spectroscopy. 1694115 7 3 theme N-linked 1127:1134 arg1 oligosaccharide 1179:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 1 4 theme alpha-fetoprotein 172:188 arg1 Determination 155:167 Determination 155:167 Determination of alpha-fetoprotein 155:188 Determination of alpha-fetoprotein is used in diagnosis of tumors and neural tube defects. 1694115 6 5 theme alpha-fetoprotein 995:1011 arg1 glycosylation 978:990 glycosylation 978:990 glycosylation of alpha-fetoprotein 978:1011 However, because the presence of different glycoforms has been reported in alpha-fetoprotein preparations, both from human sources and from other species, it was important to establish the type and extent of glycosylation of alpha-fetoprotein prepared by our method. 1694115 7 6 theme hepatomas 1213:1221 arg1 typical 1196:1202 typical 1196:1202 typical 1196:1202 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 4 7 theme alpha-fetoprotein 575:591 arg1 g 570:570 40 g 567:570 40 g of alpha-fetoprotein from culture supernatant liquid 567:623 This method, which is suitable for scaling up, allowed us to produce 40 g of alpha-fetoprotein from culture supernatant liquid through a simple purification procedure. 1694115 7 8 theme human 1207:1211 arg1 hepatomas 1213:1221 human hepatomas 1207:1221 human hepatomas 1207:1221 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 6 9 theme other 910:914 arg1 species 916:922 other species 910:922 other species 910:922 However, because the presence of different glycoforms has been reported in alpha-fetoprotein preparations, both from human sources and from other species, it was important to establish the type and extent of glycosylation of alpha-fetoprotein prepared by our method. 1694115 6 10 theme glycoforms 813:822 arg1 presence 791:798 the presence 787:798 the presence of different glycoforms 787:822 However, because the presence of different glycoforms has been reported in alpha-fetoprotein preparations, both from human sources and from other species, it was important to establish the type and extent of glycosylation of alpha-fetoprotein prepared by our method. 1694115 6 11 theme glycosylation 978:990 arg1 extent 968:973 extent 968:973 extent 968:973 However, because the presence of different glycoforms has been reported in alpha-fetoprotein preparations, both from human sources and from other species, it was important to establish the type and extent of glycosylation of alpha-fetoprotein prepared by our method. 1694115 6 11 theme glycosylation 978:990 arg1 type 959:962 type 959:962 type 959:962 However, because the presence of different glycoforms has been reported in alpha-fetoprotein preparations, both from human sources and from other species, it was important to establish the type and extent of glycosylation of alpha-fetoprotein prepared by our method. 1694115 7 12 dep biantennary 1136:1146 arg1 sialylated 1155:1164 sialylated 1155:1164 sialylated 1155:1164 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 3 13 theme cell 487:490 arg1 line 492:495 a human hepatoma cell line 470:495 a human hepatoma cell line 470:495 We have recently developed a method for the production of alpha-fetoprotein from a human hepatoma cell line. 1694115 3 14 theme alpha-fetoprotein 447:463 arg1 production 433:442 the production 429:442 the production of alpha-fetoprotein from a human hepatoma cell line 429:495 We have recently developed a method for the production of alpha-fetoprotein from a human hepatoma cell line. 1694115 5 15 theme other 755:759 arg1 sources 761:767 other sources 755:767 other sources 755:767 We have previously shown this protein to be identical to alpha-fetoprotein produced from other sources. 1694115 0 16 from alpha-fetoprotein 38:54 arg1 structure 7:15 Unique structure 0:15 Unique structure of glycopeptide from alpha-fetoprotein 0:54 Unique structure of glycopeptide from alpha-fetoprotein produced in human hepatoma cell line, as determined by 1H-nuclear magnetic resonance spectroscopy. 1694115 3 17 from line 492:495 arg1 production 433:442 the production 429:442 the production of alpha-fetoprotein from a human hepatoma cell line 429:495 We have recently developed a method for the production of alpha-fetoprotein from a human hepatoma cell line. 1694115 2 18 theme alpha-fetoprotein 272:288 arg1 advantage 310:318 an obvious advantage 299:318 an obvious advantage to the preparation of diagnostic reagents and their standardization 299:386 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 2 18 theme alpha-fetoprotein 272:288 arg1 source 262:267 A good reliable source 246:267 A good reliable source of alpha-fetoprotein 246:288 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 4 19 theme culture 598:604 arg1 supernatant 606:616 culture supernatant liquid 598:623 culture supernatant liquid 598:623 This method, which is suitable for scaling up, allowed us to produce 40 g of alpha-fetoprotein from culture supernatant liquid through a simple purification procedure. 1694115 0 20 theme Unique 0:5 arg1 structure 7:15 Unique structure 0:15 Unique structure of glycopeptide from alpha-fetoprotein 0:54 Unique structure of glycopeptide from alpha-fetoprotein produced in human hepatoma cell line, as determined by 1H-nuclear magnetic resonance spectroscopy. 1694115 0 21 theme glycopeptide 20:31 arg1 structure 7:15 Unique structure 0:15 Unique structure of glycopeptide from alpha-fetoprotein 0:54 Unique structure of glycopeptide from alpha-fetoprotein produced in human hepatoma cell line, as determined by 1H-nuclear magnetic resonance spectroscopy. 1694115 2 22 theme reliable 253:260 arg1 advantage 310:318 an obvious advantage 299:318 an obvious advantage to the preparation of diagnostic reagents and their standardization 299:386 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 2 22 theme reliable 253:260 arg1 source 262:267 A good reliable source 246:267 A good reliable source of alpha-fetoprotein 246:288 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 0 23 theme magnetic 122:129 arg1 resonance 131:139 1H-nuclear magnetic resonance 111:139 1H-nuclear magnetic resonance spectroscopy 111:152 Unique structure of glycopeptide from alpha-fetoprotein produced in human hepatoma cell line, as determined by 1H-nuclear magnetic resonance spectroscopy. 1694115 6 24 theme different 803:811 arg1 glycoforms 813:822 different glycoforms 803:822 different glycoforms 803:822 However, because the presence of different glycoforms has been reported in alpha-fetoprotein preparations, both from human sources and from other species, it was important to establish the type and extent of glycosylation of alpha-fetoprotein prepared by our method. 1694115 3 25 theme hepatoma 478:485 arg1 line 492:495 a human hepatoma cell line 470:495 a human hepatoma cell line 470:495 We have recently developed a method for the production of alpha-fetoprotein from a human hepatoma cell line. 1694115 0 26 theme 1H-nuclear 111:120 arg1 resonance 131:139 1H-nuclear magnetic resonance 111:139 1H-nuclear magnetic resonance spectroscopy 111:152 Unique structure of glycopeptide from alpha-fetoprotein produced in human hepatoma cell line, as determined by 1H-nuclear magnetic resonance spectroscopy. 1694115 6 27 theme human 887:891 arg1 sources 893:899 human sources 887:899 human sources 887:899 However, because the presence of different glycoforms has been reported in alpha-fetoprotein preparations, both from human sources and from other species, it was important to establish the type and extent of glycosylation of alpha-fetoprotein prepared by our method. 1694115 2 28 theme obvious 302:308 arg1 advantage 310:318 an obvious advantage 299:318 an obvious advantage to the preparation of diagnostic reagents and their standardization 299:386 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 2 28 theme obvious 302:308 arg1 source 262:267 A good reliable source 246:267 A good reliable source of alpha-fetoprotein 246:288 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 1 29 theme tumors 214:219 arg1 diagnosis 201:209 diagnosis 201:209 diagnosis of tumors and neural tube defects 201:243 Determination of alpha-fetoprotein is used in diagnosis of tumors and neural tube defects. 1694115 7 30 theme typical 1196:1202 arg1 oligosaccharide 1179:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 4 31 theme simple 635:640 arg1 procedure 655:663 a simple purification procedure 633:663 a simple purification procedure 633:663 This method, which is suitable for scaling up, allowed us to produce 40 g of alpha-fetoprotein from culture supernatant liquid through a simple purification procedure. 1694115 4 32 theme purification 642:653 arg1 procedure 655:663 a simple purification procedure 633:663 a simple purification procedure 633:663 This method, which is suitable for scaling up, allowed us to produce 40 g of alpha-fetoprotein from culture supernatant liquid through a simple purification procedure. 1694115 0 33 theme resonance 131:139 arg1 spectroscopy 141:152 1H-nuclear magnetic resonance spectroscopy 111:152 1H-nuclear magnetic resonance spectroscopy 111:152 Unique structure of glycopeptide from alpha-fetoprotein produced in human hepatoma cell line, as determined by 1H-nuclear magnetic resonance spectroscopy. 1694115 7 34 theme complex-type 1166:1177 arg1 oligosaccharide 1179:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 1 35 theme neural 225:230 arg1 defects 237:243 neural tube defects 225:243 neural tube defects 225:243 Determination of alpha-fetoprotein is used in diagnosis of tumors and neural tube defects. 1694115 7 36 theme biantennary 1136:1146 arg1 oligosaccharide 1179:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 7 37 theme 1H-NMR 1046:1051 arg1 spectroscopy 1053:1064 1H-NMR spectroscopy 1046:1064 1H-NMR spectroscopy 1046:1064 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 1694115 4 38 from supernatant 606:616 arg1 g 570:570 40 g 567:570 40 g of alpha-fetoprotein from culture supernatant liquid 567:623 This method, which is suitable for scaling up, allowed us to produce 40 g of alpha-fetoprotein from culture supernatant liquid through a simple purification procedure. 1694115 2 39 theme reagents 353:360 arg1 preparation 327:337 the preparation 323:337 the preparation of diagnostic reagents and their standardization 323:386 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 0 40 gly glycopeptide 20:31 arg2 glycopeptide 20:31 glycopeptide 20:31 glycopeptide 20:31 Unique structure of glycopeptide from alpha-fetoprotein produced in human hepatoma cell line, as determined by 1H-nuclear magnetic resonance spectroscopy. 1694115 6 41 gly glycosylation 978:990 arg1 alpha-fetoprotein 995:1011 alpha-fetoprotein 995:1011 alpha-fetoprotein 995:1011 However, because the presence of different glycoforms has been reported in alpha-fetoprotein preparations, both from human sources and from other species, it was important to establish the type and extent of glycosylation of alpha-fetoprotein prepared by our method. 1694115 2 42 theme diagnostic 342:351 arg1 reagents 353:360 diagnostic reagents 342:360 diagnostic reagents 342:360 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 6 43 theme alpha-fetoprotein 845:861 arg1 preparations 863:874 alpha-fetoprotein preparations 845:874 alpha-fetoprotein preparations 845:874 However, because the presence of different glycoforms has been reported in alpha-fetoprotein preparations, both from human sources and from other species, it was important to establish the type and extent of glycosylation of alpha-fetoprotein prepared by our method. 1694115 1 44 theme tube 232:235 arg1 defects 237:243 neural tube defects 225:243 neural tube defects 225:243 Determination of alpha-fetoprotein is used in diagnosis of tumors and neural tube defects. 1694115 1 45 theme defects 237:243 arg1 diagnosis 201:209 diagnosis 201:209 diagnosis of tumors and neural tube defects 201:243 Determination of alpha-fetoprotein is used in diagnosis of tumors and neural tube defects. 1694115 0 46 theme hepatoma 74:81 arg1 line 88:91 human hepatoma cell line 68:91 human hepatoma cell line 68:91 Unique structure of glycopeptide from alpha-fetoprotein produced in human hepatoma cell line, as determined by 1H-nuclear magnetic resonance spectroscopy. 1694115 3 47 theme human 472:476 arg1 line 492:495 a human hepatoma cell line 470:495 a human hepatoma cell line 470:495 We have recently developed a method for the production of alpha-fetoprotein from a human hepatoma cell line. 1694115 1 48 used used 193:196 arg2 Determination 155:167 Determination 155:167 Determination of alpha-fetoprotein 155:188 Determination of alpha-fetoprotein is used in diagnosis of tumors and neural tube defects. 1694115 4 49 theme liquid 618:623 arg1 supernatant 606:616 culture supernatant liquid 598:623 culture supernatant liquid 598:623 This method, which is suitable for scaling up, allowed us to produce 40 g of alpha-fetoprotein from culture supernatant liquid through a simple purification procedure. 1694115 0 50 theme human 68:72 arg1 line 88:91 human hepatoma cell line 68:91 human hepatoma cell line 68:91 Unique structure of glycopeptide from alpha-fetoprotein produced in human hepatoma cell line, as determined by 1H-nuclear magnetic resonance spectroscopy. 1694115 2 51 theme good 248:251 arg1 advantage 310:318 an obvious advantage 299:318 an obvious advantage to the preparation of diagnostic reagents and their standardization 299:386 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 2 51 theme good 248:251 arg1 source 262:267 A good reliable source 246:267 A good reliable source of alpha-fetoprotein 246:288 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 2 52 theme standardization 372:386 arg1 preparation 327:337 the preparation 323:337 the preparation of diagnostic reagents and their standardization 323:386 A good reliable source of alpha-fetoprotein would be an obvious advantage to the preparation of diagnostic reagents and their standardization. 1694115 7 53 link N-linked 1127:1134 arg1 oligosaccharide 1179:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 a single N-linked biantennary, fully sialylated complex-type oligosaccharide 1118:1193 By using 1H-NMR spectroscopy we were able to establish that our product contains a single N-linked biantennary, fully sialylated complex-type oligosaccharide, typical of human hepatomas. 8252542 7 0 from cells 1579:1583 arg1 subsequent 1585:1594 subsequent 1585:1594 subsequent 1585:1594 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 7 1 theme baby 1559:1562 arg1 kidney 1572:1577 baby hamster kidney 1559:1577 baby hamster kidney 1559:1577 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 8 2 theme pentamannose 1713:1724 arg1 presence 1699:1706 the presence 1695:1706 the presence of a pentamannose 1695:1724 Methylation analysis of free oligosaccharides obtained from MNL revealed the presence of a pentamannose. 8252542 2 3 theme suboptimal 427:436 arg1 doses 438:442 suboptimal doses 427:442 suboptimal doses of interleukin-2 427:459 Swainsonine augments lymphokine-activated, killer-cell induction at suboptimal doses of interleukin-2; the amount needed to increase LAK activity is 100-1000 fold higher than required to completely inhibit mannosidase II. 8252542 7 4 theme melanoma 1546:1553 arg1 cells 1579:1583 mouse B16F10 melanoma and baby hamster kidney cells 1533:1583 mouse B16F10 melanoma and baby hamster kidney cells 1533:1583 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 6 5 theme endoglycosidase 1262:1276 arg1 H 1278:1278 endoglycosidase H 1262:1278 endoglycosidase H 1262:1278 This oligosaccharide fraction was resistant to hydrolysis by endoglycosidase H, endoglycosidase F, O and N-glycanase, but was susceptible to cleavage by Jack bean alpha-mannosidase and was bound > 90% to concanavalin A-Sepharose. 8252542 3 6 from increase 712:719 arg1 incorporation 738:750 D-[3H]mannose incorporation 724:750 D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells 724:808 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 1 7 theme oligosaccharide-containing 298:323 arg1 glycoproteins 325:337 hybrid-type oligosaccharide-containing glycoproteins 286:337 hybrid-type oligosaccharide-containing glycoproteins 286:337 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 7 8 theme mouse 1533:1537 arg1 melanoma 1546:1553 mouse B16F10 melanoma 1533:1553 mouse B16F10 melanoma 1533:1553 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 4 9 theme cell 919:922 arg1 fractions 902:910 the soluble fractions 890:910 the soluble fractions of the cell 890:922 Analysis indicated accumulation of high-mannose type, free oligosaccharides in the soluble fractions of the cell. 8252542 9 10 theme free 1772:1775 arg1 oligosaccharide 1790:1804 a free high-mannose oligosaccharide 1770:1804 a free high-mannose oligosaccharide rather than expected hybrid-type structure 1770:1847 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 1 11 link asparagine-linked 230:246 arg1 glycoproteins 248:260 asparagine-linked glycoproteins 230:260 asparagine-linked glycoproteins 230:260 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 9 12 theme oligosaccharide 1790:1804 arg1 accumulation 1754:1765 the accumulation 1750:1765 the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine 1750:1920 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 3 13 theme cells 804:808 arg1 glycans 783:789 glycans 783:789 glycans of untreated cells 783:808 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 0 14 theme glycoprotein 120:131 arg1 processing 133:142 glycoprotein processing 120:142 glycoprotein processing 120:142 Accumulation of pentamannose oligosaccharides in human mononuclear leukocytes by action of swainsonine, an inhibitor of glycoprotein processing. 8252542 5 15 theme total 1128:1132 arg1 radioactivity 1134:1146 the total radioactivity 1124:1146 the total radioactivity incorporated into the glycan (oligosaccharide pool) 1124:1198 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 3 16 theme high 647:650 arg1 concentrations 664:677 these relatively high (58 microM) concentrations 630:677 these relatively high (58 microM) concentrations of swainsonine 630:692 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 7 17 theme chromatographic 1441:1455 arg1 profile 1465:1471 A similar chromatographic elution profile 1431:1471 A similar chromatographic elution profile 1431:1471 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 5 18 theme Chromatographic 925:939 arg1 analysis 941:948 Chromatographic analysis 925:948 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes 925:1028 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 9 19 from accumulation 1754:1765 arg1 treatment 1852:1860 treatment 1852:1860 treatment of cells with relatively high concentrations of swainsonine 1852:1920 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 9 20 theme hybrid-type 1827:1837 arg1 structure 1839:1847 expected hybrid-type structure 1818:1847 a free high-mannose oligosaccharide rather than expected hybrid-type structure 1770:1847 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 2 21 dep lymphokine-activated 380:399 arg1 killer-cell 402:412 killer-cell 402:412 killer-cell 402:412 Swainsonine augments lymphokine-activated, killer-cell induction at suboptimal doses of interleukin-2; the amount needed to increase LAK activity is 100-1000 fold higher than required to completely inhibit mannosidase II. 8252542 6 22 theme bean 1359:1362 arg1 alpha-mannosidase 1364:1380 Jack bean alpha-mannosidase 1354:1380 Jack bean alpha-mannosidase 1354:1380 This oligosaccharide fraction was resistant to hydrolysis by endoglycosidase H, endoglycosidase F, O and N-glycanase, but was susceptible to cleavage by Jack bean alpha-mannosidase and was bound > 90% to concanavalin A-Sepharose. 8252542 3 23 theme 3-4 703:705 arg1 increase 712:719 a 3-4 fold increase 701:719 a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells 701:808 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 5 24 theme mononuclear 1006:1016 arg1 lymphocytes 1018:1028 human mononuclear lymphocytes 1000:1028 human mononuclear lymphocytes 1000:1028 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 5 25 theme D-[2-3H 972:978 arg1 labeling 988:995 D-[2-3H]mannose labeling 972:995 D-[2-3H]mannose labeling of human mononuclear lymphocytes 972:1028 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 1 26 gly glycoproteins 248:260 arg1 glycoproteins 248:260 asparagine-linked glycoproteins 230:260 asparagine-linked glycoproteins 230:260 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 5 27 theme mannose 980:986 arg1 labeling 988:995 D-[2-3H]mannose labeling 972:995 D-[2-3H]mannose labeling of human mononuclear lymphocytes 972:1028 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 9 28 theme high 1887:1890 arg1 concentrations 1892:1905 relatively high concentrations 1876:1905 relatively high concentrations of swainsonine 1876:1920 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 5 29 theme new 1052:1054 arg1 oligosaccharide 1056:1070 a new oligosaccharide 1050:1070 a new oligosaccharide 1050:1070 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 4 30 theme type 859:862 arg1 oligosaccharides 870:885 high-mannose type, free oligosaccharides 846:885 oligosaccharides 870:885 Analysis indicated accumulation of high-mannose type, free oligosaccharides in the soluble fractions of the cell. 8252542 1 31 theme glycoproteins 325:337 arg1 accumulation 270:281 accumulation 270:281 accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells 270:356 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 8 32 theme Methylation 1622:1632 arg1 analysis 1634:1641 Methylation analysis 1622:1641 Methylation analysis of free oligosaccharides obtained from MNL 1622:1684 Methylation analysis of free oligosaccharides obtained from MNL revealed the presence of a pentamannose. 8252542 0 33 theme pentamannose 16:27 arg1 Accumulation 0:11 Accumulation 0:11 Accumulation of pentamannose 0:27 Accumulation of pentamannose oligosaccharides in human mononuclear leukocytes by action of swainsonine, an inhibitor of glycoprotein processing. 8252542 1 34 theme mammalian 342:350 arg1 cells 352:356 mammalian cells 342:356 mammalian cells 342:356 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 4 35 theme soluble 894:900 arg1 fractions 902:910 the soluble fractions 890:910 the soluble fractions of the cell 890:922 Analysis indicated accumulation of high-mannose type, free oligosaccharides in the soluble fractions of the cell. 8252542 8 36 theme oligosaccharides 1651:1666 arg1 analysis 1634:1641 Methylation analysis 1622:1641 Methylation analysis of free oligosaccharides obtained from MNL 1622:1684 Methylation analysis of free oligosaccharides obtained from MNL revealed the presence of a pentamannose. 8252542 0 37 theme mononuclear 55:65 arg1 leukocytes 67:76 human mononuclear leukocytes 49:76 human mononuclear leukocytes 49:76 Accumulation of pentamannose oligosaccharides in human mononuclear leukocytes by action of swainsonine, an inhibitor of glycoprotein processing. 8252542 5 38 contain contained 1107:1115 arg2 radioactivity 1134:1146 the total radioactivity 1124:1146 the total radioactivity incorporated into the glycan (oligosaccharide pool) 1124:1198 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 5 38 contain contained 1107:1115 arg2 % 1119:1119 36% 1117:1119 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool) 1117:1198 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 5 38 contain contained 1107:1115 arg1 swainsonine 1089:1099 swainsonine 1089:1099 swainsonine 1089:1099 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 4 39 theme free 865:868 arg1 oligosaccharides 870:885 high-mannose type, free oligosaccharides 846:885 oligosaccharides 870:885 Analysis indicated accumulation of high-mannose type, free oligosaccharides in the soluble fractions of the cell. 8252542 1 40 theme asparagine-linked 230:246 arg1 glycoproteins 248:260 asparagine-linked glycoproteins 230:260 asparagine-linked glycoproteins 230:260 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 7 41 theme hamster 1564:1570 arg1 kidney 1572:1577 baby hamster kidney 1559:1577 baby hamster kidney 1559:1577 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 3 42 dep high 647:650 arg1 microM 656:661 58 microM 653:661 58 microM 653:661 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 3 43 theme mannose 730:736 arg1 incorporation 738:750 D-[3H]mannose incorporation 724:750 D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells 724:808 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 2 44 theme interleukin-2 447:459 arg1 doses 438:442 suboptimal doses 427:442 suboptimal doses of interleukin-2 427:459 Swainsonine augments lymphokine-activated, killer-cell induction at suboptimal doses of interleukin-2; the amount needed to increase LAK activity is 100-1000 fold higher than required to completely inhibit mannosidase II. 8252542 6 45 theme Jack 1354:1357 arg1 alpha-mannosidase 1364:1380 Jack bean alpha-mannosidase 1354:1380 Jack bean alpha-mannosidase 1354:1380 This oligosaccharide fraction was resistant to hydrolysis by endoglycosidase H, endoglycosidase F, O and N-glycanase, but was susceptible to cleavage by Jack bean alpha-mannosidase and was bound > 90% to concanavalin A-Sepharose. 8252542 3 46 theme Human 581:585 arg1 lymphocytes 599:609 Human mononuclear lymphocytes 581:609 Human mononuclear lymphocytes 581:609 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 7 47 theme B16F10 1539:1544 arg1 melanoma 1546:1553 mouse B16F10 melanoma 1533:1553 mouse B16F10 melanoma 1533:1553 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 1 48 theme hybrid-type 286:296 arg1 glycoproteins 325:337 hybrid-type oligosaccharide-containing glycoproteins 286:337 hybrid-type oligosaccharide-containing glycoproteins 286:337 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 3 49 theme untreated 794:802 arg1 cells 804:808 untreated cells 794:808 untreated cells 794:808 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 1 50 theme alpha-mannosidase 183:199 arg1 Swainsonine 145:155 Swainsonine 145:155 Swainsonine 145:155 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 1 50 theme alpha-mannosidase 183:199 arg1 inhibitor 166:174 a known inhibitor 158:174 a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins 158:260 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 2 51 theme lymphokine-activated 380:399 arg1 induction 414:422 lymphokine-activated, killer-cell induction 380:422 lymphokine-activated, killer-cell induction 380:422 Swainsonine augments lymphokine-activated, killer-cell induction at suboptimal doses of interleukin-2; the amount needed to increase LAK activity is 100-1000 fold higher than required to completely inhibit mannosidase II. 8252542 5 52 theme glycan 953:958 arg1 analysis 941:948 Chromatographic analysis 925:948 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes 925:1028 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 9 53 theme high-mannose 1777:1788 arg1 oligosaccharide 1790:1804 a free high-mannose oligosaccharide 1770:1804 a free high-mannose oligosaccharide rather than expected hybrid-type structure 1770:1847 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 0 54 theme processing 133:142 arg1 swainsonine 91:101 swainsonine 91:101 swainsonine 91:101 Accumulation of pentamannose oligosaccharides in human mononuclear leukocytes by action of swainsonine, an inhibitor of glycoprotein processing. 8252542 0 54 theme processing 133:142 arg1 inhibitor 107:115 an inhibitor 104:115 an inhibitor of glycoprotein processing 104:142 Accumulation of pentamannose oligosaccharides in human mononuclear leukocytes by action of swainsonine, an inhibitor of glycoprotein processing. 8252542 6 55 theme oligosaccharide 1206:1220 arg1 fraction 1222:1229 This oligosaccharide fraction 1201:1229 This oligosaccharide fraction 1201:1229 This oligosaccharide fraction was resistant to hydrolysis by endoglycosidase H, endoglycosidase F, O and N-glycanase, but was susceptible to cleavage by Jack bean alpha-mannosidase and was bound > 90% to concanavalin A-Sepharose. 8252542 1 56 from accumulation 270:281 arg1 cells 352:356 mammalian cells 342:356 mammalian cells 342:356 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 5 57 theme radioactivity 1134:1146 arg1 radioactivity 1134:1146 the total radioactivity 1124:1146 the total radioactivity incorporated into the glycan (oligosaccharide pool) 1124:1198 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 5 57 theme radioactivity 1134:1146 arg1 % 1119:1119 36% 1117:1119 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool) 1117:1198 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 9 58 theme expected 1818:1825 arg1 structure 1839:1847 expected hybrid-type structure 1818:1847 a free high-mannose oligosaccharide rather than expected hybrid-type structure 1770:1847 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 7 59 theme elution 1457:1463 arg1 profile 1465:1471 A similar chromatographic elution profile 1431:1471 A similar chromatographic elution profile 1431:1471 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 1 60 gly glycoproteins 325:337 arg1 glycoproteins 325:337 hybrid-type oligosaccharide-containing glycoproteins 286:337 hybrid-type oligosaccharide-containing glycoproteins 286:337 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 0 61 gly glycoprotein 120:131 arg1 glycoprotein 120:131 glycoprotein processing 120:142 glycoprotein processing 120:142 Accumulation of pentamannose oligosaccharides in human mononuclear leukocytes by action of swainsonine, an inhibitor of glycoprotein processing. 8252542 9 62 theme structure 1839:1847 arg1 accumulation 1754:1765 the accumulation 1750:1765 the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine 1750:1920 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 7 63 theme similar 1433:1439 arg1 profile 1465:1471 A similar chromatographic elution profile 1431:1471 A similar chromatographic elution profile 1431:1471 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 5 64 theme human 1000:1004 arg1 lymphocytes 1018:1028 human mononuclear lymphocytes 1000:1028 human mononuclear lymphocytes 1000:1028 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 6 65 theme endoglycosidase 1281:1295 arg1 F 1297:1297 endoglycosidase F 1281:1297 endoglycosidase F 1281:1297 This oligosaccharide fraction was resistant to hydrolysis by endoglycosidase H, endoglycosidase F, O and N-glycanase, but was susceptible to cleavage by Jack bean alpha-mannosidase and was bound > 90% to concanavalin A-Sepharose. 8252542 3 66 theme swainsonine 682:692 arg1 concentrations 664:677 these relatively high (58 microM) concentrations 630:677 these relatively high (58 microM) concentrations of swainsonine 630:692 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 9 67 theme cells 1865:1869 arg1 treatment 1852:1860 treatment 1852:1860 treatment of cells with relatively high concentrations of swainsonine 1852:1920 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 0 68 theme swainsonine 91:101 arg1 action 81:86 action 81:86 action of swainsonine, an inhibitor of glycoprotein processing 81:142 Accumulation of pentamannose oligosaccharides in human mononuclear leukocytes by action of swainsonine, an inhibitor of glycoprotein processing. 8252542 1 69 theme known 160:164 arg1 Swainsonine 145:155 Swainsonine 145:155 Swainsonine 145:155 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 1 69 theme known 160:164 arg1 inhibitor 166:174 a known inhibitor 158:174 a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins 158:260 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 6 70 theme concanavalin 1405:1416 arg1 A-Sepharose 1418:1428 concanavalin A-Sepharose 1405:1428 concanavalin A-Sepharose 1405:1428 This oligosaccharide fraction was resistant to hydrolysis by endoglycosidase H, endoglycosidase F, O and N-glycanase, but was susceptible to cleavage by Jack bean alpha-mannosidase and was bound > 90% to concanavalin A-Sepharose. 8252542 5 71 theme glycan 1170:1175 arg1 pool 1194:1197 the glycan (oligosaccharide pool) 1166:1198 the glycan (oligosaccharide pool) 1166:1198 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 4 72 from accumulation 830:841 arg1 fractions 902:910 the soluble fractions 890:910 the soluble fractions of the cell 890:922 Analysis indicated accumulation of high-mannose type, free oligosaccharides in the soluble fractions of the cell. 8252542 5 73 theme oligosaccharide 1056:1070 arg1 synthesis 1037:1045 synthesis 1037:1045 synthesis of a new oligosaccharide 1037:1070 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 9 74 theme swainsonine 1910:1920 arg1 concentrations 1892:1905 relatively high concentrations 1876:1905 relatively high concentrations of swainsonine 1876:1920 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 4 75 theme high-mannose 846:857 arg1 oligosaccharides 870:885 high-mannose type, free oligosaccharides 846:885 oligosaccharides 870:885 Analysis indicated accumulation of high-mannose type, free oligosaccharides in the soluble fractions of the cell. 8252542 9 76 with treatment 1852:1860 arg1 concentrations 1892:1905 relatively high concentrations 1876:1905 relatively high concentrations of swainsonine 1876:1920 These results indicate the accumulation of a free high-mannose oligosaccharide rather than expected hybrid-type structure on treatment of cells with relatively high concentrations of swainsonine. 8252542 5 77 theme oligosaccharide 1178:1192 arg1 pool 1194:1197 the glycan (oligosaccharide pool) 1166:1198 the glycan (oligosaccharide pool) 1166:1198 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 5 78 theme lymphocytes 1018:1028 arg1 labeling 988:995 D-[2-3H]mannose labeling 972:995 D-[2-3H]mannose labeling of human mononuclear lymphocytes 972:1028 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 8 79 theme free 1646:1649 arg1 oligosaccharides 1651:1666 free oligosaccharides 1646:1666 free oligosaccharides obtained from MNL 1646:1684 Methylation analysis of free oligosaccharides obtained from MNL revealed the presence of a pentamannose. 8252542 2 80 theme LAK 492:494 arg1 activity 496:503 LAK activity 492:503 LAK activity 492:503 Swainsonine augments lymphokine-activated, killer-cell induction at suboptimal doses of interleukin-2; the amount needed to increase LAK activity is 100-1000 fold higher than required to completely inhibit mannosidase II. 8252542 0 81 theme human 49:53 arg1 leukocytes 67:76 human mononuclear leukocytes 49:76 human mononuclear leukocytes 49:76 Accumulation of pentamannose oligosaccharides in human mononuclear leukocytes by action of swainsonine, an inhibitor of glycoprotein processing. 8252542 5 82 theme swainsonine 1089:1099 arg1 microM 1079:1084 58 microM 1076:1084 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool) 1076:1198 Chromatographic analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of swainsonine, that contained 36% of the total radioactivity incorporated into the glycan (oligosaccharide pool). 8252542 3 83 theme fold 707:710 arg1 increase 712:719 a 3-4 fold increase 701:719 a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells 701:808 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 3 84 theme mononuclear 587:597 arg1 lymphocytes 599:609 Human mononuclear lymphocytes 581:609 Human mononuclear lymphocytes 581:609 Human mononuclear lymphocytes, when treated with these relatively high (58 microM) concentrations of swainsonine showed a 3-4 fold increase in D-[3H]mannose incorporation into the glycan as compared to glycans of untreated cells. 8252542 7 85 theme subsequent 1585:1594 arg1 treatment 1611:1619 D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment 1512:1619 D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment 1512:1619 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 1 86 theme glycoproteins 248:260 arg1 processing 216:225 processing 216:225 processing of asparagine-linked glycoproteins 216:260 Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing of asparagine-linked glycoproteins, causes accumulation of hybrid-type oligosaccharide-containing glycoproteins in mammalian cells. 8252542 7 87 theme kidney 1572:1577 arg1 cells 1579:1583 mouse B16F10 melanoma and baby hamster kidney cells 1533:1583 mouse B16F10 melanoma and baby hamster kidney cells 1533:1583 A similar chromatographic elution profile was obtained from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby hamster kidney cells subsequent to swainsonine treatment. 8252542 4 88 theme oligosaccharides 870:885 arg1 accumulation 830:841 accumulation 830:841 accumulation of high-mannose type, free oligosaccharides in the soluble fractions of the cell 830:922 Analysis indicated accumulation of high-mannose type, free oligosaccharides in the soluble fractions of the cell. 8038170 9 0 theme lysosomal 1751:1759 arg1 enzymes 1761:1767 lysosomal enzymes 1751:1767 lysosomal enzymes 1751:1767 Taken together, the data suggest that Sf9 cells do not synthesize high-mannose-type oligosaccharides containing mannose 6-phosphate, and consequently it appears unlikely that these cells utilize the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes. 8038170 4 1 theme oligosaccharides 570:585 arg1 type 679:682 a truncated (trimannosyl) high-mannose type 640:682 a truncated (trimannosyl) high-mannose type 640:682 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 4 1 theme oligosaccharides 570:585 arg1 two-thirds 699:708 two-thirds 699:708 two-thirds 699:708 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 4 1 theme oligosaccharides 570:585 arg1 oligosaccharides 570:585 the N-linked oligosaccharides 557:585 the N-linked oligosaccharides isolated from the Sf9-produced prorenin 557:625 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 3 2 theme ion-exchange 492:503 arg1 combination 469:479 a combination 467:479 a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography 467:551 The oligosaccharide structures on the resulting glycopeptides were analyzed by a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography. 8038170 3 3 theme liquid 531:536 arg1 chromatography 538:551 high-pressure liquid chromatography 517:551 high-pressure liquid chromatography 517:551 The oligosaccharide structures on the resulting glycopeptides were analyzed by a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography. 8038170 4 4 theme truncated 642:650 arg1 type 679:682 a truncated (trimannosyl) high-mannose type 640:682 a truncated (trimannosyl) high-mannose type 640:682 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 8 5 theme lysates 1308:1314 arg1 Blotting 1287:1294 Blotting 1287:1294 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor 1287:1404 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 4 6 attach linked 746:751 arg1 N-acetylglucosamine 769:787 the reducing N-acetylglucosamine 756:787 the reducing N-acetylglucosamine 756:787 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 4 6 attach linked 746:751 arg2 residue 738:744 a fucose residue 729:744 a fucose residue linked to the reducing N-acetylglucosamine 729:787 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 9 7 theme Sf9 1527:1529 arg1 cells 1531:1535 Sf9 cells 1527:1535 Sf9 cells 1527:1535 Taken together, the data suggest that Sf9 cells do not synthesize high-mannose-type oligosaccharides containing mannose 6-phosphate, and consequently it appears unlikely that these cells utilize the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes. 8038170 0 8 theme 6-phosphate 109:119 arg1 signal 133:138 the mannose 6-phosphate recognition signal 97:138 the mannose 6-phosphate recognition signal 97:138 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 5 9 theme structures 850:859 arg1 mixture 821:827 a mixture 819:827 a mixture of high-mannose-type structures containing six, seven, or eight mannose residues 819:908 The remaining 2% constituted a mixture of high-mannose-type structures containing six, seven, or eight mannose residues; none of these structures were core-fucosylated. 8038170 2 10 dep In 276:277 arg1 vivo 279:282 vivo 279:282 vivo 279:282 In vivo labeled prorenin was isolated by immunoprecipitation from the culture medium and digested with Pronase. 8038170 9 11 theme mannose 1601:1607 arg1 6-phosphate 1609:1619 mannose 6-phosphate 1601:1619 mannose 6-phosphate 1601:1619 Taken together, the data suggest that Sf9 cells do not synthesize high-mannose-type oligosaccharides containing mannose 6-phosphate, and consequently it appears unlikely that these cells utilize the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes. 8038170 4 12 theme high-mannose 666:677 arg1 type 679:682 a truncated (trimannosyl) high-mannose type 640:682 a truncated (trimannosyl) high-mannose type 640:682 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 6 13 theme recombinant 1013:1023 arg1 prorenin 1025:1032 recombinant prorenin 1013:1032 recombinant prorenin synthesized by Sf9 cells 1013:1057 None of the oligosaccharide structures recovered from recombinant prorenin synthesized by Sf9 cells were phosphorylated or contained any other form of charge. 8038170 8 14 theme receptor 1397:1404 arg1 form 1346:1349 an 125I-labeled, soluble form 1321:1349 form 1346:1349 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 0 15 theme cell 66:69 arg1 line 71:74 the insect cell line 55:74 the insect cell line Sf9 55:78 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 5 16 theme mannose 893:899 arg1 residues 901:908 six, seven, or eight mannose residues 872:908 six, seven, or eight mannose residues 872:908 The remaining 2% constituted a mixture of high-mannose-type structures containing six, seven, or eight mannose residues; none of these structures were core-fucosylated. 8038170 0 17 from Glycosylation 0:12 arg1 cells 48:52 insect cells 41:52 insect cells 41:52 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 6 18 theme oligosaccharide 971:985 arg1 structures 987:996 the oligosaccharide structures 967:996 the oligosaccharide structures recovered from recombinant prorenin synthesized by Sf9 cells 967:1057 None of the oligosaccharide structures recovered from recombinant prorenin synthesized by Sf9 cells were phosphorylated or contained any other form of charge. 8038170 5 19 gly core-fucosylated 941:956 arg1 none 911:914 none 911:914 none of these structures 911:934 The remaining 2% constituted a mixture of high-mannose-type structures containing six, seven, or eight mannose residues; none of these structures were core-fucosylated. 8038170 0 20 from cells 48:52 arg1 Glycosylation 0:12 Glycosylation 0:12 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 0:139 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 5 21 contain containing 861:870 arg1 structures 850:859 high-mannose-type structures 832:859 high-mannose-type structures containing six, seven, or eight mannose residues 832:908 The remaining 2% constituted a mixture of high-mannose-type structures containing six, seven, or eight mannose residues; none of these structures were core-fucosylated. 8038170 5 21 contain containing 861:870 arg2 residues 901:908 six, seven, or eight mannose residues 872:908 six, seven, or eight mannose residues 872:908 The remaining 2% constituted a mixture of high-mannose-type structures containing six, seven, or eight mannose residues; none of these structures were core-fucosylated. 8038170 4 22 theme reducing 760:767 arg1 N-acetylglucosamine 769:787 the reducing N-acetylglucosamine 756:787 the reducing N-acetylglucosamine 756:787 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 7 23 from background 1240:1249 arg1 lysates 1254:1260 lysates 1254:1260 lysates prepared from Sf9 cells 1254:1284 Furthermore, assays for UDP-GlcNAc-lysosomal-enzyme N-acetylglucosamine phosphotransferase demonstrated no activity above background in lysates prepared from Sf9 cells. 8038170 5 24 theme structures 925:934 arg1 none 911:914 none 911:914 none of these structures 911:934 The remaining 2% constituted a mixture of high-mannose-type structures containing six, seven, or eight mannose residues; none of these structures were core-fucosylated. 8038170 8 25 theme mannose 1449:1455 arg1 signal 1481:1486 the mannose 6-phosphate recognition signal 1445:1486 the mannose 6-phosphate recognition signal 1445:1486 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 9 26 theme mannose 1688:1694 arg1 receptor 1708:1715 mannose 6-phosphate receptor 1688:1715 mannose 6-phosphate receptor 1688:1715 Taken together, the data suggest that Sf9 cells do not synthesize high-mannose-type oligosaccharides containing mannose 6-phosphate, and consequently it appears unlikely that these cells utilize the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes. 8038170 0 27 theme recombinant 17:27 arg1 prorenin 29:36 recombinant prorenin 17:36 recombinant prorenin in insect cells 17:52 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 8 28 theme mannose 1377:1383 arg1 receptor 1397:1404 the cation-independent mannose 6-phosphate receptor 1354:1404 the cation-independent mannose 6-phosphate receptor 1354:1404 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 8 29 theme recognition 1469:1479 arg1 signal 1481:1486 the mannose 6-phosphate recognition signal 1445:1486 the mannose 6-phosphate recognition signal 1445:1486 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 8 30 theme Sf9 1299:1301 arg1 lysates 1308:1314 Sf9 cell lysates 1299:1314 Sf9 cell lysates 1299:1314 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 9 31 theme 6-phosphate 1696:1706 arg1 receptor 1708:1715 mannose 6-phosphate receptor 1688:1715 mannose 6-phosphate receptor 1688:1715 Taken together, the data suggest that Sf9 cells do not synthesize high-mannose-type oligosaccharides containing mannose 6-phosphate, and consequently it appears unlikely that these cells utilize the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes. 8038170 6 32 theme Sf9 1049:1051 arg1 cells 1053:1057 Sf9 cells 1049:1057 Sf9 cells 1049:1057 None of the oligosaccharide structures recovered from recombinant prorenin synthesized by Sf9 cells were phosphorylated or contained any other form of charge. 8038170 7 33 theme N-acetylglucosamine 1170:1188 arg1 phosphotransferase 1190:1207 UDP-GlcNAc-lysosomal-enzyme N-acetylglucosamine phosphotransferase 1142:1207 UDP-GlcNAc-lysosomal-enzyme N-acetylglucosamine phosphotransferase 1142:1207 Furthermore, assays for UDP-GlcNAc-lysosomal-enzyme N-acetylglucosamine phosphotransferase demonstrated no activity above background in lysates prepared from Sf9 cells. 8038170 9 34 theme mediated 1717:1724 arg1 pathway 1726:1732 the mannose 6-phosphate receptor mediated pathway 1684:1732 the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes 1684:1767 Taken together, the data suggest that Sf9 cells do not synthesize high-mannose-type oligosaccharides containing mannose 6-phosphate, and consequently it appears unlikely that these cells utilize the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes. 8038170 2 35 theme culture 346:352 arg1 medium 354:359 the culture medium 342:359 the culture medium 342:359 In vivo labeled prorenin was isolated by immunoprecipitation from the culture medium and digested with Pronase. 8038170 0 36 dep Glycosylation 0:12 arg1 express 89:95 express 89:95 does not express the mannose 6-phosphate recognition signal 80:138 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 6 37 theme charge 1110:1115 arg1 form 1102:1105 any other form 1092:1105 any other form of charge 1092:1115 None of the oligosaccharide structures recovered from recombinant prorenin synthesized by Sf9 cells were phosphorylated or contained any other form of charge. 8038170 9 38 theme enzymes 1761:1767 arg1 targeting 1738:1746 targeting 1738:1746 targeting of lysosomal enzymes 1738:1767 Taken together, the data suggest that Sf9 cells do not synthesize high-mannose-type oligosaccharides containing mannose 6-phosphate, and consequently it appears unlikely that these cells utilize the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes. 8038170 4 39 theme N-linked 561:568 arg1 oligosaccharides 570:585 the N-linked oligosaccharides 557:585 the N-linked oligosaccharides isolated from the Sf9-produced prorenin 557:625 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 3 40 theme high-pressure 517:529 arg1 chromatography 538:551 high-pressure liquid chromatography 517:551 high-pressure liquid chromatography 517:551 The oligosaccharide structures on the resulting glycopeptides were analyzed by a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography. 8038170 2 41 attach isolated 305:312 arg2 prorenin 292:299 In vivo labeled prorenin 276:299 In vivo labeled prorenin 276:299 In vivo labeled prorenin was isolated by immunoprecipitation from the culture medium and digested with Pronase. 8038170 2 41 attach isolated 305:312 arg1 medium 354:359 the culture medium 342:359 the culture medium 342:359 In vivo labeled prorenin was isolated by immunoprecipitation from the culture medium and digested with Pronase. 8038170 5 42 theme remaining 794:802 arg1 % 805:805 The remaining 2% 790:805 The remaining 2% 790:805 The remaining 2% constituted a mixture of high-mannose-type structures containing six, seven, or eight mannose residues; none of these structures were core-fucosylated. 8038170 2 43 theme labeled 284:290 arg1 prorenin 292:299 In vivo labeled prorenin 276:299 In vivo labeled prorenin 276:299 In vivo labeled prorenin was isolated by immunoprecipitation from the culture medium and digested with Pronase. 8038170 8 44 theme cell 1303:1306 arg1 lysates 1308:1314 Sf9 cell lysates 1299:1314 Sf9 cell lysates 1299:1314 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 0 45 theme mannose 101:107 arg1 signal 133:138 the mannose 6-phosphate recognition signal 97:138 the mannose 6-phosphate recognition signal 97:138 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 2 46 theme In 276:277 arg1 prorenin 292:299 In vivo labeled prorenin 276:299 In vivo labeled prorenin 276:299 In vivo labeled prorenin was isolated by immunoprecipitation from the culture medium and digested with Pronase. 8038170 8 47 theme 6-phosphate 1385:1395 arg1 receptor 1397:1404 the cation-independent mannose 6-phosphate receptor 1354:1404 the cation-independent mannose 6-phosphate receptor 1354:1404 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 0 48 theme recognition 121:131 arg1 signal 133:138 the mannose 6-phosphate recognition signal 97:138 the mannose 6-phosphate recognition signal 97:138 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 1 49 theme recombinant 167:177 arg1 baculovirus 179:189 a recombinant baculovirus 165:189 a recombinant baculovirus containing the gene for human prorenin 165:228 Sf9 cells infected with a recombinant baculovirus containing the gene for human prorenin were cultured in the presence of [3H]mannose. 8038170 5 50 theme high-mannose-type 832:848 arg1 structures 850:859 high-mannose-type structures 832:859 high-mannose-type structures containing six, seven, or eight mannose residues 832:908 The remaining 2% constituted a mixture of high-mannose-type structures containing six, seven, or eight mannose residues; none of these structures were core-fucosylated. 8038170 8 51 theme 125I-labeled 1324:1335 arg1 form 1346:1349 an 125I-labeled, soluble form 1321:1349 form 1346:1349 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 9 52 theme high-mannose-type 1555:1571 arg1 oligosaccharides 1573:1588 high-mannose-type oligosaccharides 1555:1588 high-mannose-type oligosaccharides containing mannose 6-phosphate 1555:1619 Taken together, the data suggest that Sf9 cells do not synthesize high-mannose-type oligosaccharides containing mannose 6-phosphate, and consequently it appears unlikely that these cells utilize the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes. 8038170 8 53 theme soluble 1338:1344 arg1 form 1346:1349 an 125I-labeled, soluble form 1321:1349 form 1346:1349 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 3 54 theme chromatography 538:551 arg1 combination 469:479 a combination 467:479 a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography 467:551 The oligosaccharide structures on the resulting glycopeptides were analyzed by a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography. 8038170 8 55 with Blotting 1287:1294 arg1 form 1346:1349 an 125I-labeled, soluble form 1321:1349 form 1346:1349 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 0 56 theme insect 59:64 arg1 line 71:74 the insect cell line 55:74 the insect cell line Sf9 55:78 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 4 57 attach isolated 587:594 arg1 prorenin 618:625 the Sf9-produced prorenin 601:625 the Sf9-produced prorenin 601:625 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 4 57 attach isolated 587:594 arg2 oligosaccharides 570:585 the N-linked oligosaccharides 557:585 the N-linked oligosaccharides isolated from the Sf9-produced prorenin 557:625 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 0 58 from prorenin 29:36 arg1 cells 48:52 insect cells 41:52 insect cells 41:52 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 8 59 theme cation-independent 1358:1375 arg1 receptor 1397:1404 the cation-independent mannose 6-phosphate receptor 1354:1404 the cation-independent mannose 6-phosphate receptor 1354:1404 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 7 60 theme Sf9 1276:1278 arg1 cells 1280:1284 Sf9 cells 1276:1284 Sf9 cells 1276:1284 Furthermore, assays for UDP-GlcNAc-lysosomal-enzyme N-acetylglucosamine phosphotransferase demonstrated no activity above background in lysates prepared from Sf9 cells. 8038170 1 61 theme Sf9 141:143 arg1 cells 145:149 Sf9 cells 141:149 Sf9 cells infected with a recombinant baculovirus containing the gene for human prorenin 141:228 Sf9 cells infected with a recombinant baculovirus containing the gene for human prorenin were cultured in the presence of [3H]mannose. 8038170 8 62 contain carrying 1436:1443 arg1 proteins 1427:1434 any proteins 1423:1434 any proteins carrying the mannose 6-phosphate recognition signal 1423:1486 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 8 62 contain carrying 1436:1443 arg2 signal 1481:1486 the mannose 6-phosphate recognition signal 1445:1486 the mannose 6-phosphate recognition signal 1445:1486 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 4 63 theme type 679:682 arg1 type 679:682 a truncated (trimannosyl) high-mannose type 640:682 a truncated (trimannosyl) high-mannose type 640:682 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 4 63 theme type 679:682 arg1 two-thirds 699:708 two-thirds 699:708 two-thirds 699:708 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 4 63 theme type 679:682 arg1 oligosaccharides 570:585 the N-linked oligosaccharides 557:585 the N-linked oligosaccharides isolated from the Sf9-produced prorenin 557:625 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 6 64 theme structures 987:996 arg1 None 959:962 None 959:962 None of the oligosaccharide structures recovered from recombinant prorenin synthesized by Sf9 cells 959:1057 None of the oligosaccharide structures recovered from recombinant prorenin synthesized by Sf9 cells were phosphorylated or contained any other form of charge. 8038170 6 65 theme other 1096:1100 arg1 form 1102:1105 any other form 1092:1105 any other form of charge 1092:1115 None of the oligosaccharide structures recovered from recombinant prorenin synthesized by Sf9 cells were phosphorylated or contained any other form of charge. 8038170 3 66 theme resulting 426:434 arg1 glycopeptides 436:448 the resulting glycopeptides 422:448 the resulting glycopeptides 422:448 The oligosaccharide structures on the resulting glycopeptides were analyzed by a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography. 8038170 0 67 dep line 71:74 arg1 Sf9 76:78 Sf9 76:78 the insect cell line Sf9 55:78 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 0 68 theme prorenin 29:36 arg1 Glycosylation 0:12 Glycosylation 0:12 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 0:139 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 9 69 contain containing 1590:1599 arg1 oligosaccharides 1573:1588 high-mannose-type oligosaccharides 1555:1588 high-mannose-type oligosaccharides containing mannose 6-phosphate 1555:1619 Taken together, the data suggest that Sf9 cells do not synthesize high-mannose-type oligosaccharides containing mannose 6-phosphate, and consequently it appears unlikely that these cells utilize the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes. 8038170 9 69 contain containing 1590:1599 arg2 6-phosphate 1609:1619 mannose 6-phosphate 1601:1619 mannose 6-phosphate 1601:1619 Taken together, the data suggest that Sf9 cells do not synthesize high-mannose-type oligosaccharides containing mannose 6-phosphate, and consequently it appears unlikely that these cells utilize the mannose 6-phosphate receptor mediated pathway for targeting of lysosomal enzymes. 8038170 4 70 theme fucose 731:736 arg1 residue 738:744 a fucose residue 729:744 a fucose residue linked to the reducing N-acetylglucosamine 729:787 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 0 71 theme insect 41:46 arg1 cells 48:52 insect cells 41:52 insect cells 41:52 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 1 72 theme mannose 267:273 arg1 presence 251:258 the presence 247:258 the presence of [3H]mannose 247:273 Sf9 cells infected with a recombinant baculovirus containing the gene for human prorenin were cultured in the presence of [3H]mannose. 8038170 0 73 gly Glycosylation 0:12 arg1 prorenin 29:36 recombinant prorenin 17:36 recombinant prorenin in insect cells 17:52 Glycosylation of recombinant prorenin in insect cells: the insect cell line Sf9 does not express the mannose 6-phosphate recognition signal. 8038170 3 74 theme oligosaccharide 392:406 arg1 structures 408:417 The oligosaccharide structures 388:417 The oligosaccharide structures on the resulting glycopeptides 388:448 The oligosaccharide structures on the resulting glycopeptides were analyzed by a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography. 8038170 8 75 theme 6-phosphate 1457:1467 arg1 signal 1481:1486 the mannose 6-phosphate recognition signal 1445:1486 the mannose 6-phosphate recognition signal 1445:1486 Blotting of Sf9 cell lysates with an 125I-labeled, soluble form of the cation-independent mannose 6-phosphate receptor failed to detect any proteins carrying the mannose 6-phosphate recognition signal. 8038170 7 76 theme UDP-GlcNAc-lysosomal-enzyme 1142:1168 arg1 phosphotransferase 1190:1207 UDP-GlcNAc-lysosomal-enzyme N-acetylglucosamine phosphotransferase 1142:1207 UDP-GlcNAc-lysosomal-enzyme N-acetylglucosamine phosphotransferase 1142:1207 Furthermore, assays for UDP-GlcNAc-lysosomal-enzyme N-acetylglucosamine phosphotransferase demonstrated no activity above background in lysates prepared from Sf9 cells. 8038170 3 77 gly glycopeptides 436:448 arg2 glycopeptides 436:448 the resulting glycopeptides 422:448 the resulting glycopeptides 422:448 The oligosaccharide structures on the resulting glycopeptides were analyzed by a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography. 8038170 3 78 theme lectin 484:489 arg1 combination 469:479 a combination 467:479 a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography 467:551 The oligosaccharide structures on the resulting glycopeptides were analyzed by a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography. 8038170 4 79 theme Sf9-produced 605:616 arg1 prorenin 618:625 the Sf9-produced prorenin 601:625 the Sf9-produced prorenin 601:625 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 1 80 contain containing 191:200 arg2 gene 206:209 the gene 202:209 the gene for human prorenin 202:228 Sf9 cells infected with a recombinant baculovirus containing the gene for human prorenin were cultured in the presence of [3H]mannose. 8038170 1 80 contain containing 191:200 arg1 baculovirus 179:189 a recombinant baculovirus 165:189 a recombinant baculovirus containing the gene for human prorenin 165:228 Sf9 cells infected with a recombinant baculovirus containing the gene for human prorenin were cultured in the presence of [3H]mannose. 8038170 3 81 from structures 408:417 arg1 glycopeptides 436:448 the resulting glycopeptides 422:448 the resulting glycopeptides 422:448 The oligosaccharide structures on the resulting glycopeptides were analyzed by a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography. 8038170 1 82 theme human 215:219 arg1 prorenin 221:228 human prorenin 215:228 human prorenin 215:228 Sf9 cells infected with a recombinant baculovirus containing the gene for human prorenin were cultured in the presence of [3H]mannose. 8038170 4 83 link N-linked 561:568 arg1 oligosaccharides 570:585 the N-linked oligosaccharides 557:585 the N-linked oligosaccharides isolated from the Sf9-produced prorenin 557:625 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 4 84 dep truncated 642:650 arg1 trimannosyl 653:663 trimannosyl 653:663 trimannosyl 653:663 Of the N-linked oligosaccharides isolated from the Sf9-produced prorenin, 98% were of a truncated (trimannosyl) high-mannose type, approximately two-thirds of which contained a fucose residue linked to the reducing N-acetylglucosamine. 8038170 3 85 theme paper 506:510 arg1 combination 469:479 a combination 467:479 a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography 467:551 The oligosaccharide structures on the resulting glycopeptides were analyzed by a combination of lectin, ion-exchange, paper, and high-pressure liquid chromatography. 10929010 8 0 theme galactose 1423:1431 arg1 attachment 1433:1442 galactose attachment 1423:1442 galactose attachment 1423:1442 Furthermore, the presence of the galactosyltransferase appeared to reduce the number of paucimannosidic structures, which suggests that galactose attachment inhibits the ability of hexosaminidase activity to remove the terminal N-acetylglucosamine. 10929010 1 1 theme transferrin 154:164 arg1 N-glycans 129:137 The N-glycans 125:137 The N-glycans of human serum transferrin produced in Trichopulsia ni cells 125:198 The N-glycans of human serum transferrin produced in Trichopulsia ni cells were analyzed to examine N-linked oligosaccharide processing in insect cells. 10929010 1 2 theme insect 264:269 arg1 cells 271:275 insect cells 264:275 insect cells 264:275 The N-glycans of human serum transferrin produced in Trichopulsia ni cells were analyzed to examine N-linked oligosaccharide processing in insect cells. 10929010 2 3 theme multiple 377:384 arg1 glycoforms 398:407 multiple transferrin glycoforms 377:407 multiple transferrin glycoforms 377:407 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 4 4 theme attached 646:653 arg1 oligosaccharides 655:670 The attached oligosaccharides 642:670 The attached oligosaccharides 642:670 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 8 5 theme terminal 1506:1513 arg1 N-acetylglucosamine 1515:1533 the terminal N-acetylglucosamine 1502:1533 the terminal N-acetylglucosamine 1502:1533 Furthermore, the presence of the galactosyltransferase appeared to reduce the number of paucimannosidic structures, which suggests that galactose attachment inhibits the ability of hexosaminidase activity to remove the terminal N-acetylglucosamine. 10929010 4 6 theme Asn-linked 863:872 arg1 N-acetylglucosamine 874:892 the Asn-linked N-acetylglucosamine 859:892 the Asn-linked N-acetylglucosamine 859:892 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 7 7 theme residues 1277:1284 arg1 presence 1231:1238 the presence 1227:1238 the presence of zero, one, or two attached fucose residues 1227:1284 The galactose attachments were exclusive to the alpha(1, 3)-mannose branch and the structures varied by the presence of zero, one, or two attached fucose residues. 10929010 2 8 theme intra- 309:314 arg1 fractions 342:350 the intra- and extracellular protein fractions 305:350 the intra- and extracellular protein fractions 305:350 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 4 9 theme high 681:684 arg1 mannose 686:692 high mannose 681:692 high mannose 681:692 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 9 10 theme paucimannosidic 1586:1600 arg1 N-glycans 1602:1610 paucimannosidic N-glycans 1586:1610 paucimannosidic N-glycans 1586:1610 The ability to promote galactosylation and reduce paucimannosidic N-glycans suggests that the oligosaccharide processing pathway in insect cells may be manipulated to mimic more closely that of mammalian cells. 10929010 3 11 theme performance 607:617 arg1 chromatography 626:639 three-dimensional high performance liquid chromatography 584:639 three-dimensional high performance liquid chromatography 584:639 Consequently, the N-glycan structures of transferrin in the culture medium were determined using three-dimensional high performance liquid chromatography. 10929010 2 12 theme transferrin 386:396 arg1 glycoforms 398:407 multiple transferrin glycoforms 377:407 multiple transferrin glycoforms 377:407 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 3 13 theme transferrin 528:538 arg1 structures 514:523 the N-glycan structures 501:523 the N-glycan structures of transferrin in the culture medium 501:560 Consequently, the N-glycan structures of transferrin in the culture medium were determined using three-dimensional high performance liquid chromatography. 10929010 0 14 theme galactosyltransferase 102:122 arg1 effects 81:87 effects 81:87 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 0:123 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 10929010 6 15 theme -galactosyltransferase 1023:1044 arg1 oligosaccharides 1091:1106 -galactosyltransferase three additional galactose-containing hybrid oligosaccharides 1023:1106 -galactosyltransferase three additional galactose-containing hybrid oligosaccharides 1023:1106 However, when transferrin was coexpressed with beta(1,4)-galactosyltransferase three additional galactose-containing hybrid oligosaccharides were obtained. 10929010 6 16 theme galactose-containing 1063:1082 arg1 oligosaccharides 1091:1106 -galactosyltransferase three additional galactose-containing hybrid oligosaccharides 1023:1106 -galactosyltransferase three additional galactose-containing hybrid oligosaccharides 1023:1106 However, when transferrin was coexpressed with beta(1,4)-galactosyltransferase three additional galactose-containing hybrid oligosaccharides were obtained. 10929010 0 17 theme mammalian 92:100 arg1 galactosyltransferase 102:122 mammalian galactosyltransferase 92:122 mammalian galactosyltransferase 92:122 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 10929010 7 18 theme alpha 1171:1175 arg1 branch 1191:1196 the alpha(1, 3)-mannose branch 1167:1196 branch 1191:1196 The galactose attachments were exclusive to the alpha(1, 3)-mannose branch and the structures varied by the presence of zero, one, or two attached fucose residues. 10929010 3 19 theme three-dimensional 584:600 arg1 chromatography 626:639 three-dimensional high performance liquid chromatography 584:639 three-dimensional high performance liquid chromatography 584:639 Consequently, the N-glycan structures of transferrin in the culture medium were determined using three-dimensional high performance liquid chromatography. 10929010 1 20 theme Trichopulsia 178:189 arg1 cells 194:198 Trichopulsia ni cells 178:198 Trichopulsia ni cells 178:198 The N-glycans of human serum transferrin produced in Trichopulsia ni cells were analyzed to examine N-linked oligosaccharide processing in insect cells. 10929010 4 21 link Asn-linked 863:872 arg1 N-acetylglucosamine 874:892 the Asn-linked N-acetylglucosamine 859:892 the Asn-linked N-acetylglucosamine 859:892 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 2 22 theme fractions 342:350 arg1 radiolabeling 288:300 Metabolic radiolabeling 278:300 Metabolic radiolabeling of the intra- and extracellular protein fractions 278:350 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 1 23 theme ni 191:192 arg1 cells 194:198 Trichopulsia ni cells 178:198 Trichopulsia ni cells 178:198 The N-glycans of human serum transferrin produced in Trichopulsia ni cells were analyzed to examine N-linked oligosaccharide processing in insect cells. 10929010 0 24 theme N-glycan 0:7 arg1 patterns 9:16 N-glycan patterns 0:16 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 0:123 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 10929010 9 25 theme insect 1668:1673 arg1 cells 1675:1679 insect cells 1668:1679 insect cells 1668:1679 The ability to promote galactosylation and reduce paucimannosidic N-glycans suggests that the oligosaccharide processing pathway in insect cells may be manipulated to mimic more closely that of mammalian cells. 10929010 1 26 link N-linked 225:232 arg1 processing 250:259 N-linked oligosaccharide processing 225:259 N-linked oligosaccharide processing in insect cells 225:275 The N-glycans of human serum transferrin produced in Trichopulsia ni cells were analyzed to examine N-linked oligosaccharide processing in insect cells. 10929010 2 27 theme protein 334:340 arg1 fractions 342:350 the intra- and extracellular protein fractions 305:350 the intra- and extracellular protein fractions 305:350 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 2 28 theme molecular 414:422 arg1 weights 424:430 molecular weights 414:430 molecular weights lower than that observed for native human transferrin 414:484 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 0 29 theme human 21:25 arg1 transferrin 27:37 human transferrin 21:37 human transferrin produced in Trichoplusia ni insect cells 21:78 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 10929010 6 30 theme hybrid 1084:1089 arg1 oligosaccharides 1091:1106 -galactosyltransferase three additional galactose-containing hybrid oligosaccharides 1023:1106 -galactosyltransferase three additional galactose-containing hybrid oligosaccharides 1023:1106 However, when transferrin was coexpressed with beta(1,4)-galactosyltransferase three additional galactose-containing hybrid oligosaccharides were obtained. 10929010 2 31 gly glycoforms 398:407 arg1 transferrin 386:396 multiple transferrin glycoforms 377:407 multiple transferrin glycoforms 377:407 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 2 32 theme extracellular 320:332 arg1 fractions 342:350 the intra- and extracellular protein fractions 305:350 the intra- and extracellular protein fractions 305:350 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 8 33 theme paucimannosidic 1375:1389 arg1 structures 1391:1400 paucimannosidic structures 1375:1400 paucimannosidic structures 1375:1400 Furthermore, the presence of the galactosyltransferase appeared to reduce the number of paucimannosidic structures, which suggests that galactose attachment inhibits the ability of hexosaminidase activity to remove the terminal N-acetylglucosamine. 10929010 2 34 theme native 461:466 arg1 transferrin 474:484 native human transferrin 461:484 native human transferrin 461:484 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 2 35 theme human 468:472 arg1 transferrin 474:484 native human transferrin 461:484 native human transferrin 461:484 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 5 36 theme sialic 903:908 arg1 acid 910:913 sialic acid 903:913 sialic acid 903:913 Neither sialic acid nor galactose was detected on any of the N-glycans. 10929010 4 37 theme structures 757:766 arg1 % 746:746 over 50% 739:746 over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine 739:892 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 4 37 theme structures 757:766 arg1 structures 757:766 these structures 751:766 these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine 751:892 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 3 38 theme culture 547:553 arg1 medium 555:560 the culture medium 543:560 the culture medium 543:560 Consequently, the N-glycan structures of transferrin in the culture medium were determined using three-dimensional high performance liquid chromatography. 10929010 7 39 theme -mannose 1182:1189 arg1 branch 1191:1196 the alpha(1, 3)-mannose branch 1167:1196 branch 1191:1196 The galactose attachments were exclusive to the alpha(1, 3)-mannose branch and the structures varied by the presence of zero, one, or two attached fucose residues. 10929010 6 40 dep obtained 1113:1120 arg1 1,4 1019:1021 1,4 1019:1021 1,4 1019:1021 However, when transferrin was coexpressed with beta(1,4)-galactosyltransferase three additional galactose-containing hybrid oligosaccharides were obtained. 10929010 6 41 theme additional 1052:1061 arg1 oligosaccharides 1091:1106 -galactosyltransferase three additional galactose-containing hybrid oligosaccharides 1023:1106 -galactosyltransferase three additional galactose-containing hybrid oligosaccharides 1023:1106 However, when transferrin was coexpressed with beta(1,4)-galactosyltransferase three additional galactose-containing hybrid oligosaccharides were obtained. 10929010 7 42 theme attached 1261:1268 arg1 residues 1277:1284 zero, one, or two attached fucose residues 1243:1284 zero, one, or two attached fucose residues 1243:1284 The galactose attachments were exclusive to the alpha(1, 3)-mannose branch and the structures varied by the presence of zero, one, or two attached fucose residues. 10929010 0 43 theme transferrin 27:37 arg1 patterns 9:16 N-glycan patterns 0:16 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 0:123 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 10929010 9 44 theme oligosaccharide 1630:1644 arg1 pathway 1657:1663 the oligosaccharide processing pathway 1626:1663 the oligosaccharide processing pathway in insect cells 1626:1679 The ability to promote galactosylation and reduce paucimannosidic N-glycans suggests that the oligosaccharide processing pathway in insect cells may be manipulated to mimic more closely that of mammalian cells. 10929010 7 45 theme fucose 1270:1275 arg1 residues 1277:1284 zero, one, or two attached fucose residues 1243:1284 zero, one, or two attached fucose residues 1243:1284 The galactose attachments were exclusive to the alpha(1, 3)-mannose branch and the structures varied by the presence of zero, one, or two attached fucose residues. 10929010 0 46 theme Trichoplusia 51:62 arg1 cells 74:78 Trichoplusia ni insect cells 51:78 Trichoplusia ni insect cells 51:78 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 10929010 5 47 located detected 933:940 arg1 any 945:947 any 945:947 any 945:947 Neither sialic acid nor galactose was detected on any of the N-glycans. 10929010 5 47 located detected 933:940 arg2 galactose 919:927 galactose 919:927 galactose 919:927 Neither sialic acid nor galactose was detected on any of the N-glycans. 10929010 5 47 located detected 933:940 arg2 acid 910:913 sialic acid 903:913 sialic acid 903:913 Neither sialic acid nor galactose was detected on any of the N-glycans. 10929010 1 48 from processing 250:259 arg1 cells 271:275 insect cells 264:275 insect cells 264:275 The N-glycans of human serum transferrin produced in Trichopulsia ni cells were analyzed to examine N-linked oligosaccharide processing in insect cells. 10929010 2 49 with presence 365:372 arg1 weights 424:430 molecular weights 414:430 molecular weights lower than that observed for native human transferrin 414:484 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 9 50 theme processing 1646:1655 arg1 pathway 1657:1663 the oligosaccharide processing pathway 1626:1663 the oligosaccharide processing pathway in insect cells 1626:1679 The ability to promote galactosylation and reduce paucimannosidic N-glycans suggests that the oligosaccharide processing pathway in insect cells may be manipulated to mimic more closely that of mammalian cells. 10929010 9 51 from pathway 1657:1663 arg1 cells 1675:1679 insect cells 1668:1679 insect cells 1668:1679 The ability to promote galactosylation and reduce paucimannosidic N-glycans suggests that the oligosaccharide processing pathway in insect cells may be manipulated to mimic more closely that of mammalian cells. 10929010 9 52 theme mammalian 1730:1738 arg1 cells 1740:1744 mammalian cells 1730:1744 mammalian cells 1730:1744 The ability to promote galactosylation and reduce paucimannosidic N-glycans suggests that the oligosaccharide processing pathway in insect cells may be manipulated to mimic more closely that of mammalian cells. 10929010 8 53 theme hexosaminidase 1468:1481 arg1 activity 1483:1490 hexosaminidase activity 1468:1490 hexosaminidase activity 1468:1490 Furthermore, the presence of the galactosyltransferase appeared to reduce the number of paucimannosidic structures, which suggests that galactose attachment inhibits the ability of hexosaminidase activity to remove the terminal N-acetylglucosamine. 10929010 8 54 theme structures 1391:1400 arg1 number 1365:1370 the number 1361:1370 the number of paucimannosidic structures 1361:1400 Furthermore, the presence of the galactosyltransferase appeared to reduce the number of paucimannosidic structures, which suggests that galactose attachment inhibits the ability of hexosaminidase activity to remove the terminal N-acetylglucosamine. 10929010 7 55 theme galactose 1127:1135 arg1 attachments 1137:1147 The galactose attachments 1123:1147 The galactose attachments 1123:1147 The galactose attachments were exclusive to the alpha(1, 3)-mannose branch and the structures varied by the presence of zero, one, or two attached fucose residues. 10929010 7 55 theme galactose 1127:1135 arg1 exclusive 1154:1162 exclusive 1154:1162 exclusive 1154:1162 The galactose attachments were exclusive to the alpha(1, 3)-mannose branch and the structures varied by the presence of zero, one, or two attached fucose residues. 10929010 4 56 attach linked 849:854 arg1 N-acetylglucosamine 874:892 the Asn-linked N-acetylglucosamine 859:892 the Asn-linked N-acetylglucosamine 859:892 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 4 56 attach linked 849:854 arg2 fucose 783:788 one fucose 779:788 one fucose 779:788 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 2 57 theme Metabolic 278:286 arg1 radiolabeling 288:300 Metabolic radiolabeling 278:300 Metabolic radiolabeling of the intra- and extracellular protein fractions 278:350 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 3 58 from structures 514:523 arg1 medium 555:560 the culture medium 543:560 the culture medium 543:560 Consequently, the N-glycan structures of transferrin in the culture medium were determined using three-dimensional high performance liquid chromatography. 10929010 3 59 theme liquid 619:624 arg1 chromatography 626:639 three-dimensional high performance liquid chromatography 584:639 three-dimensional high performance liquid chromatography 584:639 Consequently, the N-glycan structures of transferrin in the culture medium were determined using three-dimensional high performance liquid chromatography. 10929010 1 60 theme N-linked 225:232 arg1 processing 250:259 N-linked oligosaccharide processing 225:259 N-linked oligosaccharide processing in insect cells 225:275 The N-glycans of human serum transferrin produced in Trichopulsia ni cells were analyzed to examine N-linked oligosaccharide processing in insect cells. 10929010 8 61 theme galactosyltransferase 1320:1340 arg1 presence 1304:1311 the presence 1300:1311 the presence of the galactosyltransferase 1300:1340 Furthermore, the presence of the galactosyltransferase appeared to reduce the number of paucimannosidic structures, which suggests that galactose attachment inhibits the ability of hexosaminidase activity to remove the terminal N-acetylglucosamine. 10929010 3 62 theme high 602:605 arg1 chromatography 626:639 three-dimensional high performance liquid chromatography 584:639 three-dimensional high performance liquid chromatography 584:639 Consequently, the N-glycan structures of transferrin in the culture medium were determined using three-dimensional high performance liquid chromatography. 10929010 2 63 theme glycoforms 398:407 arg1 presence 365:372 the presence 361:372 the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin 361:484 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 1 64 theme oligosaccharide 234:248 arg1 processing 250:259 N-linked oligosaccharide processing 225:259 N-linked oligosaccharide processing in insect cells 225:275 The N-glycans of human serum transferrin produced in Trichopulsia ni cells were analyzed to examine N-linked oligosaccharide processing in insect cells. 10929010 0 65 theme insect 67:72 arg1 cells 74:78 Trichoplusia ni insect cells 51:78 Trichoplusia ni insect cells 51:78 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 10929010 8 66 theme activity 1483:1490 arg1 ability 1457:1463 the ability 1453:1463 the ability of hexosaminidase activity to remove the terminal N-acetylglucosamine 1453:1533 Furthermore, the presence of the galactosyltransferase appeared to reduce the number of paucimannosidic structures, which suggests that galactose attachment inhibits the ability of hexosaminidase activity to remove the terminal N-acetylglucosamine. 10929010 0 67 dep patterns 9:16 arg1 effects 81:87 effects 81:87 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 0:123 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 10929010 3 68 theme N-glycan 505:512 arg1 structures 514:523 the N-glycan structures 501:523 the N-glycan structures of transferrin in the culture medium 501:560 Consequently, the N-glycan structures of transferrin in the culture medium were determined using three-dimensional high performance liquid chromatography. 10929010 1 69 theme human 142:146 arg1 transferrin 154:164 human serum transferrin 142:164 human serum transferrin produced in Trichopulsia ni cells 142:198 The N-glycans of human serum transferrin produced in Trichopulsia ni cells were analyzed to examine N-linked oligosaccharide processing in insect cells. 10929010 2 70 theme lower 432:436 arg1 weights 424:430 molecular weights 414:430 molecular weights lower than that observed for native human transferrin 414:484 Metabolic radiolabeling of the intra- and extracellular protein fractions revealed the presence of multiple transferrin glycoforms with molecular weights lower than that observed for native human transferrin. 10929010 0 71 theme ni 64:65 arg1 cells 74:78 Trichoplusia ni insect cells 51:78 Trichoplusia ni insect cells 51:78 N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells: effects of mammalian galactosyltransferase. 10929010 4 72 contain containing 768:777 arg2 alpha 836:840 alpha 836:840 alpha(1,3)- 836:846 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 4 72 contain containing 768:777 arg1 structures 757:766 these structures 751:766 these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine 751:892 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 4 72 contain containing 768:777 arg2 fucose 783:788 one fucose 779:788 one fucose 779:788 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 4 72 contain containing 768:777 arg2 alpha 820:824 alpha(1,6)- 820:830 alpha(1,6)- 820:830 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 4 72 contain containing 768:777 arg2 alpha 791:795 alpha(1,6)- 791:801 alpha(1,6)- 791:801 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 4 72 contain containing 768:777 arg2 1,3 842:844 1,3 842:844 1,3 842:844 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 4 72 contain containing 768:777 arg2 fucoses 811:817 two fucoses 807:817 two fucoses 807:817 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 4 73 theme hybrid 716:721 arg1 structures 723:732 hybrid structures 716:732 hybrid structures 716:732 The attached oligosaccharides included high mannose, paucimannosidic, and hybrid structures with over 50% of these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)- and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. 10929010 1 74 theme serum 148:152 arg1 transferrin 154:164 human serum transferrin 142:164 human serum transferrin produced in Trichopulsia ni cells 142:198 The N-glycans of human serum transferrin produced in Trichopulsia ni cells were analyzed to examine N-linked oligosaccharide processing in insect cells. 10683228 8 0 theme oligosaccharides 1300:1315 arg1 oligosaccharides 1300:1315 authentic standard oligosaccharides 1281:1315 authentic standard oligosaccharides 1281:1315 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 8 0 theme oligosaccharides 1300:1315 arg1 amounts 1270:1276 increasing amounts 1259:1276 increasing amounts of authentic standard oligosaccharides 1259:1315 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 10 1 theme structural 1748:1757 arg1 isomers 1759:1765 the structural isomers 1744:1765 the structural isomers of sialyllacto-N-tetraose 1744:1791 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 8 2 from increments 1348:1357 arg1 values 1371:1376 detected values 1362:1376 detected values 1362:1376 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 4 3 theme underivatized 418:430 arg1 oligosaccharides 439:454 underivatized acidic oligosaccharides 418:454 underivatized acidic oligosaccharides 418:454 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm proved to be sensitive to the femtomole level. 10683228 5 4 dep 3'-sialyllactose 615:630 arg1 6'-sialyllactose 633:648 6'-sialyllactose 633:648 6'-sialyllactose 633:648 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 5 4 dep 3'-sialyllactose 615:630 arg1 disialomonofucosyllacto-N-neohexaose 852:887 disialomonofucosyllacto-N-neohexaose 852:887 disialomonofucosyllacto-N-neohexaose 852:887 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 5 4 dep 3'-sialyllactose 615:630 arg1 disialyltetraose 695:710 disialyltetraose 695:710 disialyltetraose 695:710 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 5 4 dep 3'-sialyllactose 615:630 arg1 3'-sialyl-3-fucosyllactose 713:738 3'-sialyl-3-fucosyllactose 713:738 3'-sialyl-3-fucosyllactose 713:738 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 5 4 dep 3'-sialyllactose 615:630 arg1 sialyllacto-N-neotetraose-c 793:819 sialyllacto-N-neotetraose-c 793:819 sialyllacto-N-neotetraose-c 793:819 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 5 4 dep 3'-sialyllactose 615:630 arg1 3'-sialyllactosamine 651:670 3'-sialyllactosamine 651:670 3'-sialyllactosamine 651:670 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 5 4 dep 3'-sialyllactose 615:630 arg1 disialyllacto-N-tetraose 822:845 disialyllacto-N-tetraose 822:845 disialyllacto-N-tetraose 822:845 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 5 4 dep 3'-sialyllactose 615:630 arg1 6'-sialyllactosamine 673:692 6'-sialyllactosamine 673:692 6'-sialyllactosamine 673:692 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 5 4 dep 3'-sialyllactose 615:630 arg1 sialyllacto-N-tetraose-a 741:764 sialyllacto-N-tetraose-a 741:764 sialyllacto-N-tetraose-a 741:764 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 5 4 dep 3'-sialyllactose 615:630 arg1 sialyllacto-N-tetraose-b 767:790 sialyllacto-N-tetraose-b 767:790 sialyllacto-N-tetraose-b 767:790 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 2 5 theme Neutral 168:174 arg1 oligosaccharides 181:196 Neutral milk oligosaccharides 168:196 Neutral milk oligosaccharides 168:196 Neutral milk oligosaccharides vary among individuals and over the course of lactation. 10683228 8 6 theme positive 1339:1346 arg1 increments 1348:1357 the expected positive increments 1326:1357 the expected positive increments in detected values 1326:1376 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 3 7 theme such 264:267 arg1 variation 269:277 such variation 264:277 such variation in the acidic milk oligosaccharides 264:313 To study such variation in the acidic milk oligosaccharides, a sensitive, convenient, quantitative method is needed. 10683228 4 8 theme oligosaccharides 439:454 arg1 electrophoresis 399:413 High-performance capillary electrophoresis 372:413 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm 372:496 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm proved to be sensitive to the femtomole level. 10683228 5 9 dep nonasaccharide 599:612 arg1 3'-sialyllactose 615:630 3'-sialyllactose 615:630 3'-sialyllactose 615:630 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 3 10 dep sensitive 318:326 arg1 quantitative 341:352 quantitative 341:352 quantitative 341:352 To study such variation in the acidic milk oligosaccharides, a sensitive, convenient, quantitative method is needed. 10683228 3 10 dep sensitive 318:326 arg1 convenient 329:338 convenient 329:338 convenient 329:338 To study such variation in the acidic milk oligosaccharides, a sensitive, convenient, quantitative method is needed. 10683228 11 11 theme sensitive 1799:1807 arg1 method 1830:1835 This sensitive, highly reproducible method 1794:1835 This sensitive, highly reproducible method 1794:1835 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 0 12 theme High-performance 0:15 arg1 electrophoresis 27:41 High-performance capillary electrophoresis 0:41 High-performance capillary electrophoresis of sialylated oligosaccharides of human milk 0:86 High-performance capillary electrophoresis of sialylated oligosaccharides of human milk. 10683228 4 13 theme High-performance 372:387 arg1 electrophoresis 399:413 High-performance capillary electrophoresis 372:413 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm 372:496 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm proved to be sensitive to the femtomole level. 10683228 8 14 theme other 1436:1440 arg1 components 1447:1456 other milk components 1436:1456 other milk components 1436:1456 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 3 15 theme acidic 286:291 arg1 oligosaccharides 298:313 the acidic milk oligosaccharides 282:313 the acidic milk oligosaccharides 282:313 To study such variation in the acidic milk oligosaccharides, a sensitive, convenient, quantitative method is needed. 10683228 4 16 from nm 495:496 arg1 detection 461:469 detection 461:469 detection by UV absorbance at 205 nm 461:496 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm proved to be sensitive to the femtomole level. 10683228 10 17 from profiles 1653:1660 arg1 donors 1693:1698 different donors 1683:1698 different donors 1683:1698 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 2 18 theme lactation 244:252 arg1 course 234:239 the course 230:239 the course of lactation 230:252 Neutral milk oligosaccharides vary among individuals and over the course of lactation. 10683228 7 19 theme interference 1161:1172 arg1 evidence 1136:1143 no evidence 1133:1143 no evidence of quantitative interference of one oligosaccharide with another 1133:1208 There was no evidence of quantitative interference of one oligosaccharide with another. 10683228 7 20 theme oligosaccharide 1181:1195 arg1 interference 1161:1172 quantitative interference 1148:1172 quantitative interference of one oligosaccharide with another 1148:1208 There was no evidence of quantitative interference of one oligosaccharide with another. 10683228 10 21 from donors 1693:1698 arg1 profiles 1653:1660 oligosaccharide profiles 1637:1660 oligosaccharide profiles of milk samples from different donors 1637:1698 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 10 21 from donors 1693:1698 arg1 samples 1670:1676 milk samples 1665:1676 milk samples from different donors 1665:1698 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 4 22 theme UV 474:475 arg1 absorbance 477:486 UV absorbance 474:486 UV absorbance 474:486 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm proved to be sensitive to the femtomole level. 10683228 0 23 theme milk 83:86 arg1 oligosaccharides 57:72 sialylated oligosaccharides 46:72 sialylated oligosaccharides of human milk 46:86 High-performance capillary electrophoresis of sialylated oligosaccharides of human milk. 10683228 10 24 theme oligosaccharide 1637:1651 arg1 profiles 1653:1660 oligosaccharide profiles 1637:1660 oligosaccharide profiles of milk samples from different donors 1637:1698 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 9 25 theme sialylated 1487:1496 arg1 oligosaccharides 1505:1520 the major sialylated acidic oligosaccharides 1477:1520 the major sialylated acidic oligosaccharides of pooled human milk 1477:1541 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 10 26 theme different 1683:1691 arg1 donors 1693:1698 different donors 1683:1698 different donors 1683:1698 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 5 27 theme baseline 905:912 arg1 resolutions 914:924 baseline resolutions 905:924 baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers 905:992 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 9 28 theme oligosaccharides 1505:1520 arg1 identities 1463:1472 The identities 1459:1472 The identities of the major sialylated acidic oligosaccharides of pooled human milk 1459:1541 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 0 29 theme oligosaccharides 57:72 arg1 electrophoresis 27:41 High-performance capillary electrophoresis 0:41 High-performance capillary electrophoresis of sialylated oligosaccharides of human milk 0:86 High-performance capillary electrophoresis of sialylated oligosaccharides of human milk. 10683228 10 30 theme samples 1670:1676 arg1 profiles 1653:1660 oligosaccharide profiles 1637:1660 oligosaccharide profiles of milk samples from different donors 1637:1698 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 5 31 theme isomers 986:992 arg1 resolutions 914:924 baseline resolutions 905:924 baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers 905:992 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 9 32 theme pooled 1525:1530 arg1 milk 1538:1541 pooled human milk 1525:1541 pooled human milk 1525:1541 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 9 33 theme milk 1538:1541 arg1 oligosaccharides 1505:1520 the major sialylated acidic oligosaccharides 1477:1520 the major sialylated acidic oligosaccharides of pooled human milk 1477:1541 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 8 34 theme pooled 1228:1233 arg1 milk 1241:1244 pooled human milk 1228:1244 pooled human milk 1228:1244 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 1 35 theme enteric 128:134 arg1 pathogens 136:144 enteric pathogens 128:144 enteric pathogens 128:144 Oligosaccharides in human milk inhibit enteric pathogens in vitro and in vivo. 10683228 0 36 theme sialylated 46:55 arg1 oligosaccharides 57:72 sialylated oligosaccharides 46:72 sialylated oligosaccharides of human milk 46:86 High-performance capillary electrophoresis of sialylated oligosaccharides of human milk. 10683228 2 37 theme milk 176:179 arg1 oligosaccharides 181:196 Neutral milk oligosaccharides 168:196 Neutral milk oligosaccharides 168:196 Neutral milk oligosaccharides vary among individuals and over the course of lactation. 10683228 5 38 theme other 969:973 arg1 isomers 986:992 other structural isomers 969:992 other structural isomers 969:992 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 6 39 with reproducible 1060:1071 arg1 coefficient 1080:1090 a coefficient 1078:1090 a coefficient of variation between 4 and 9% 1078:1120 Peak areas were linear from 30 to 2000 pg and were reproducible with a coefficient of variation between 4 and 9%. 10683228 9 40 theme previous 1570:1577 arg1 studies 1579:1585 previous studies 1570:1585 previous studies employing other analytical methods 1570:1620 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 8 41 theme increasing 1259:1268 arg1 oligosaccharides 1300:1315 authentic standard oligosaccharides 1281:1315 authentic standard oligosaccharides 1281:1315 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 8 41 theme increasing 1259:1268 arg1 amounts 1270:1276 increasing amounts 1259:1276 increasing amounts of authentic standard oligosaccharides 1259:1315 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 6 42 theme Peak 1009:1012 arg1 areas 1014:1018 Peak areas 1009:1018 Peak areas 1009:1018 Peak areas were linear from 30 to 2000 pg and were reproducible with a coefficient of variation between 4 and 9%. 10683228 6 43 dep 2000 1043:1046 arg1 to 1040:1041 to 1040:1041 to 1040:1041 Peak areas were linear from 30 to 2000 pg and were reproducible with a coefficient of variation between 4 and 9%. 10683228 10 44 theme sialyllacto-N-tetraose 1770:1791 arg1 isomers 1759:1765 the structural isomers 1744:1765 the structural isomers of sialyllacto-N-tetraose 1744:1791 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 11 45 theme simple 1851:1856 arg1 workup 1865:1870 only simple sample workup 1846:1870 only simple sample workup 1846:1870 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 9 46 theme analytical 1603:1612 arg1 methods 1614:1620 other analytical methods 1597:1620 other analytical methods 1597:1620 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 8 47 theme standard 1291:1298 arg1 oligosaccharides 1300:1315 authentic standard oligosaccharides 1281:1315 authentic standard oligosaccharides 1281:1315 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 4 48 theme acidic 432:437 arg1 oligosaccharides 439:454 underivatized acidic oligosaccharides 418:454 underivatized acidic oligosaccharides 418:454 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm proved to be sensitive to the femtomole level. 10683228 11 49 theme acidic 1923:1928 arg1 oligosaccharides 1930:1945 human milk acidic oligosaccharides 1912:1945 human milk acidic oligosaccharides 1912:1945 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 11 50 dep sensitive 1799:1807 arg1 reproducible 1817:1828 reproducible 1817:1828 reproducible 1817:1828 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 6 51 from pg 1048:1049 arg1 linear 1025:1030 linear 1025:1030 linear 1025:1030 Peak areas were linear from 30 to 2000 pg and were reproducible with a coefficient of variation between 4 and 9%. 10683228 11 52 theme human 1912:1916 arg1 oligosaccharides 1930:1945 human milk acidic oligosaccharides 1912:1945 human milk acidic oligosaccharides 1912:1945 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 8 53 theme expected 1330:1337 arg1 increments 1348:1357 the expected positive increments 1326:1357 the expected positive increments in detected values 1326:1376 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 4 54 theme capillary 389:397 arg1 electrophoresis 399:413 High-performance capillary electrophoresis 372:413 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm 372:496 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm proved to be sensitive to the femtomole level. 10683228 11 55 with relationship 1980:1991 arg1 diseases 1998:2005 diseases 1998:2005 diseases of infants 1998:2016 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 8 56 theme detected 1362:1369 arg1 values 1371:1376 detected values 1362:1376 detected values 1362:1376 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 3 57 theme milk 293:296 arg1 oligosaccharides 298:313 the acidic milk oligosaccharides 282:313 the acidic milk oligosaccharides 282:313 To study such variation in the acidic milk oligosaccharides, a sensitive, convenient, quantitative method is needed. 10683228 8 58 theme milk 1442:1445 arg1 components 1447:1456 other milk components 1436:1456 other milk components 1436:1456 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 8 59 theme quantitative 1390:1401 arg1 recovery 1403:1410 quantitative recovery 1390:1410 quantitative recovery 1390:1410 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 6 60 theme variation 1095:1103 arg1 coefficient 1080:1090 a coefficient 1078:1090 a coefficient of variation between 4 and 9% 1078:1120 Peak areas were linear from 30 to 2000 pg and were reproducible with a coefficient of variation between 4 and 9%. 10683228 3 61 theme sensitive 318:326 arg1 method 354:359 a sensitive, convenient, quantitative method 316:359 a sensitive, convenient, quantitative method 316:359 To study such variation in the acidic milk oligosaccharides, a sensitive, convenient, quantitative method is needed. 10683228 7 62 theme quantitative 1148:1159 arg1 interference 1161:1172 quantitative interference 1148:1172 quantitative interference of one oligosaccharide with another 1148:1208 There was no evidence of quantitative interference of one oligosaccharide with another. 10683228 11 63 theme infants 2010:2016 arg1 diseases 1998:2005 diseases 1998:2005 diseases of infants 1998:2016 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 5 64 theme standard 552:559 arg1 oligosaccharides 561:576 Eleven standard oligosaccharides 545:576 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) 545:888 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 4 65 theme femtomole 528:536 arg1 level 538:542 the femtomole level 524:542 the femtomole level 524:542 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm proved to be sensitive to the femtomole level. 10683228 9 66 gly sialylated 1487:1496 arg1 oligosaccharides 1505:1520 the major sialylated acidic oligosaccharides 1477:1520 the major sialylated acidic oligosaccharides of pooled human milk 1477:1541 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 5 67 theme 3'-sialyllactose 929:944 arg1 resolutions 914:924 baseline resolutions 905:924 baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers 905:992 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 10 68 theme profiles 1653:1660 arg1 Comparison 1623:1632 Comparison 1623:1632 Comparison of oligosaccharide profiles of milk samples from different donors 1623:1698 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 9 69 theme major 1481:1485 arg1 oligosaccharides 1505:1520 the major sialylated acidic oligosaccharides 1477:1520 the major sialylated acidic oligosaccharides of pooled human milk 1477:1541 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 7 70 with interference 1161:1172 arg1 another 1202:1208 another 1202:1208 another 1202:1208 There was no evidence of quantitative interference of one oligosaccharide with another. 10683228 9 71 theme acidic 1498:1503 arg1 oligosaccharides 1505:1520 the major sialylated acidic oligosaccharides 1477:1520 the major sialylated acidic oligosaccharides of pooled human milk 1477:1541 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 0 72 theme capillary 17:25 arg1 electrophoresis 27:41 High-performance capillary electrophoresis 0:41 High-performance capillary electrophoresis of sialylated oligosaccharides of human milk 0:86 High-performance capillary electrophoresis of sialylated oligosaccharides of human milk. 10683228 1 73 theme human 109:113 arg1 milk 115:118 human milk 109:118 human milk 109:118 Oligosaccharides in human milk inhibit enteric pathogens in vitro and in vivo. 10683228 11 74 from variations 1898:1907 arg1 oligosaccharides 1930:1945 human milk acidic oligosaccharides 1912:1945 human milk acidic oligosaccharides 1912:1945 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 10 75 theme milk 1665:1668 arg1 samples 1670:1676 milk samples 1665:1676 milk samples from different donors 1665:1698 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 9 76 theme human 1532:1536 arg1 milk 1538:1541 pooled human milk 1525:1541 pooled human milk 1525:1541 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 8 77 theme human 1235:1239 arg1 milk 1241:1244 pooled human milk 1228:1244 pooled human milk 1228:1244 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 10 78 theme extensive 1709:1717 arg1 variation 1719:1727 extensive variation 1709:1727 extensive variation 1709:1727 Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. 10683228 5 79 theme 6'-sialyllactose 947:962 arg1 resolutions 914:924 baseline resolutions 905:924 baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers 905:992 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 3 80 from variation 269:277 arg1 oligosaccharides 298:313 the acidic milk oligosaccharides 282:313 the acidic milk oligosaccharides 282:313 To study such variation in the acidic milk oligosaccharides, a sensitive, convenient, quantitative method is needed. 10683228 4 81 with electrophoresis 399:413 arg1 detection 461:469 detection 461:469 detection by UV absorbance at 205 nm 461:496 High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm proved to be sensitive to the femtomole level. 10683228 11 82 theme milk 1918:1921 arg1 oligosaccharides 1930:1945 human milk acidic oligosaccharides 1912:1945 human milk acidic oligosaccharides 1912:1945 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 0 83 theme human 77:81 arg1 milk 83:86 human milk 77:86 human milk 77:86 High-performance capillary electrophoresis of sialylated oligosaccharides of human milk. 10683228 11 84 theme possible 1971:1978 arg1 relationship 1980:1991 their possible relationship 1965:1991 their possible relationship with diseases of infants 1965:2016 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 8 85 theme amounts 1270:1276 arg1 addition 1247:1254 addition 1247:1254 addition of increasing amounts of authentic standard oligosaccharides 1247:1315 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 0 86 gly sialylated 46:55 arg1 oligosaccharides 57:72 sialylated oligosaccharides 46:72 sialylated oligosaccharides of human milk 46:86 High-performance capillary electrophoresis of sialylated oligosaccharides of human milk. 10683228 11 87 theme sample 1858:1863 arg1 workup 1865:1870 only simple sample workup 1846:1870 only simple sample workup 1846:1870 This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. 10683228 9 88 theme studies 1579:1585 arg1 results 1559:1565 the results 1555:1565 the results of previous studies employing other analytical methods 1555:1620 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 10683228 8 89 theme authentic 1281:1289 arg1 oligosaccharides 1300:1315 authentic standard oligosaccharides 1281:1315 authentic standard oligosaccharides 1281:1315 In studies using pooled human milk, addition of increasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. 10683228 5 90 theme structural 975:984 arg1 isomers 986:992 other structural isomers 969:992 other structural isomers 969:992 Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. 10683228 1 91 from Oligosaccharides 89:104 arg1 milk 115:118 human milk 109:118 human milk 109:118 Oligosaccharides in human milk inhibit enteric pathogens in vitro and in vivo. 10683228 9 92 theme other 1597:1601 arg1 methods 1614:1620 other analytical methods 1597:1620 other analytical methods 1597:1620 The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. 6628386 2 0 theme NeuAc 551:555 arg1 Glc 580:582 NeuAc(alpha 2-6)Gal(beta 1-4)Glc 551:582 NeuAc(alpha 2-6)Gal(beta 1-4)Glc 551:582 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 1 theme beta 648:651 arg1 Glc 657:659 NeuAc(alpha 2-3)Gal(beta 1-4)Glc 628:659 NeuAc(alpha 2-3)Gal(beta 1-4)Glc 628:659 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 5 2 from sialyloligosaccharides 1132:1153 arg1 urine 1158:1162 urine 1158:1162 urine 1158:1162 The predominating sialyloligosaccharides in urine were compounds 3 and 4. 6628386 2 3 theme NeuAc 588:592 arg1 GlcNAc 617:622 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc 588:622 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc 588:622 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 1 4 theme ion-exchange 271:282 arg1 chromatography 284:297 ion-exchange chromatography 271:297 ion-exchange chromatography 271:297 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 1 4 theme ion-exchange 271:282 arg1 adsorption 243:252 charcoal adsorption 234:252 charcoal adsorption 234:252 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 6 5 theme binding 1351:1357 arg1 specificity 1359:1369 binding specificity 1351:1369 binding specificity for sialyl(alpha 2-3)galactosides 1351:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 6 6 theme sialyl 1375:1380 arg1 galactosides 1392:1403 sialyl(alpha 2-3)galactosides 1375:1403 sialyl(alpha 2-3)galactosides 1375:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 2 7 theme derivatives 416:426 arg1 chromatography 366:379 gas-liquid chromatography 355:379 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation 355:492 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 8 theme Gal 722:724 arg1 alpha 744:748 alpha 2-6 744:752 alpha 2-6 744:752 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 8 theme Gal 722:724 arg1 [Neu-Ac 736:742 NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac 706:742 NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6) 706:753 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 0 9 theme human 116:120 arg1 urine 122:126 normal human urine 109:126 normal human urine 109:126 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 4 10 theme catabolic 1003:1011 arg1 pathway 1013:1019 a catabolic pathway 1001:1019 a catabolic pathway involving cleavage of the carbohydrate-peptide linkage by an endo-N-acetylgalactosaminidase 1001:1111 The presence of compound 5 in urine may suggest that it derives from glycoproteins through a catabolic pathway involving cleavage of the carbohydrate-peptide linkage by an endo-N-acetylgalactosaminidase. 6628386 2 11 theme alpha 594:598 arg1 GlcNAc 617:622 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc 588:622 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc 588:622 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 12 theme Structural 326:335 arg1 studies 337:343 Structural studies 326:343 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation 326:492 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 0 13 theme normal 109:114 arg1 urine 122:126 normal human urine 109:126 normal human urine 109:126 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 6 14 theme Escherichia 1321:1331 arg1 strains 1338:1344 uropathogenic Escherichia coli strains 1307:1344 uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides 1307:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 6 15 theme compounds 1212:1220 arg1 predominance 1192:1203 The predominance 1188:1203 The predominance of the compounds with the sialyl(alpha 2-3) linkage 1188:1255 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 2 16 theme NeuAc 665:669 arg1 GlcNAc 695:700 NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc 665:700 NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc 665:700 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 17 dep Glc 580:582 arg1 alpha 744:748 alpha 2-6 744:752 alpha 2-6 744:752 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 17 dep Glc 580:582 arg1 GlcNAc 617:622 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc 588:622 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc 588:622 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 17 dep Glc 580:582 arg1 Glc 657:659 NeuAc(alpha 2-3)Gal(beta 1-4)Glc 628:659 NeuAc(alpha 2-3)Gal(beta 1-4)Glc 628:659 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 17 dep Glc 580:582 arg1 2 585:585 2 585:585 2 585:585 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 17 dep Glc 580:582 arg1 3 625:625 3 625:625 3 625:625 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 17 dep Glc 580:582 arg1 GlcNAc 695:700 NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc 665:700 NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc 665:700 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 17 dep Glc 580:582 arg1 [Neu-Ac 736:742 NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac 706:742 NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6) 706:753 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 17 dep Glc 580:582 arg1 4 662:662 4 662:662 4 662:662 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 17 dep Glc 580:582 arg1 5 703:703 5 703:703 5 703:703 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 6 18 theme 2-3 1244:1246 arg1 linkage 1249:1255 the sialyl(alpha 2-3) linkage 1227:1255 the sialyl(alpha 2-3) linkage 1227:1255 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 2 19 dep [NeuAc 800:805 arg1 NeuAc 770:774 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc 767:805 NeuAc 770:774 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 0 20 gly sialylglycopeptide 85:102 arg1 sialyloligosaccharides 56:77 five major sialyloligosaccharides 45:77 five major sialyloligosaccharides 45:77 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 0 20 gly sialylglycopeptide 85:102 arg1 urine 122:126 normal human urine 109:126 normal human urine 109:126 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 0 20 gly sialylglycopeptide 85:102 arg2 sialylglycopeptide 85:102 a sialylglycopeptide 83:102 a sialylglycopeptide from normal human urine 83:126 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 2 21 theme glycosidase 451:461 arg1 treatments 463:472 glycosidase treatments 451:472 glycosidase treatments 451:472 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 6 22 theme recent 1287:1292 arg1 discovery 1294:1302 the recent discovery 1283:1302 the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides 1283:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 2 23 theme CrO3 479:482 arg1 oxidation 484:492 CrO3 oxidation 479:492 CrO3 oxidation 479:492 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 24 theme beta 608:611 arg1 GlcNAc 617:622 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc 588:622 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc 588:622 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 25 theme alpha 634:638 arg1 Glc 657:659 NeuAc(alpha 2-3)Gal(beta 1-4)Glc 628:659 NeuAc(alpha 2-3)Gal(beta 1-4)Glc 628:659 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 26 theme treatments 463:472 arg1 chromatography 366:379 gas-liquid chromatography 355:379 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation 355:492 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 3 27 theme free 892:895 arg1 form 897:900 a free form 890:900 a free form 890:900 Compounds 4, 5, and 6 have not been described in a free form before. 6628386 4 28 theme linkage 1068:1074 arg1 cleavage 1031:1038 cleavage 1031:1038 cleavage of the carbohydrate-peptide linkage by an endo-N-acetylgalactosaminidase 1031:1111 The presence of compound 5 in urine may suggest that it derives from glycoproteins through a catabolic pathway involving cleavage of the carbohydrate-peptide linkage by an endo-N-acetylgalactosaminidase. 6628386 6 29 theme sialyl 1231:1236 arg1 linkage 1249:1255 the sialyl(alpha 2-3) linkage 1227:1255 the sialyl(alpha 2-3) linkage 1227:1255 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 1 30 theme normal 212:217 arg1 urine 225:229 normal human urine 212:229 normal human urine 212:229 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 1 31 theme paper 304:308 arg1 chromatography 310:323 paper chromatography 304:323 paper chromatography 304:323 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 1 31 theme paper 304:308 arg1 adsorption 243:252 charcoal adsorption 234:252 charcoal adsorption 234:252 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 2 32 theme Gal 604:606 arg1 GlcNAc 617:622 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc 588:622 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc 588:622 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 33 theme NeuAc 628:632 arg1 Glc 657:659 NeuAc(alpha 2-3)Gal(beta 1-4)Glc 628:659 NeuAc(alpha 2-3)Gal(beta 1-4)Glc 628:659 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 34 theme gas-liquid 355:364 arg1 chromatography 366:379 gas-liquid chromatography 355:379 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation 355:492 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 6 35 dep Escherichia 1321:1331 arg1 coli 1333:1336 coli 1333:1336 coli 1333:1336 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 1 36 theme human 219:223 arg1 urine 225:229 normal human urine 212:229 normal human urine 212:229 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 2 37 theme following 508:516 arg1 structures 518:527 the following structures 504:527 the following structures for the compounds 504:545 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 4 38 theme carbohydrate-peptide 1047:1066 arg1 linkage 1068:1074 the carbohydrate-peptide linkage 1043:1074 the carbohydrate-peptide linkage 1043:1074 The presence of compound 5 in urine may suggest that it derives from glycoproteins through a catabolic pathway involving cleavage of the carbohydrate-peptide linkage by an endo-N-acetylgalactosaminidase. 6628386 5 39 theme predominating 1118:1130 arg1 compounds 1169:1177 compounds 3 and 4 1169:1185 compounds 3 and 4 1169:1185 The predominating sialyloligosaccharides in urine were compounds 3 and 4. 6628386 5 39 theme predominating 1118:1130 arg1 sialyloligosaccharides 1132:1153 The predominating sialyloligosaccharides 1114:1153 The predominating sialyloligosaccharides in urine 1114:1162 The predominating sialyloligosaccharides in urine were compounds 3 and 4. 6628386 6 40 theme 2-3 1388:1390 arg1 galactosides 1392:1403 sialyl(alpha 2-3)galactosides 1375:1403 sialyl(alpha 2-3)galactosides 1375:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 6 41 theme strains 1338:1344 arg1 discovery 1294:1302 the recent discovery 1283:1302 the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides 1283:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 0 42 theme structural 14:23 arg1 characterization 25:40 structural characterization 14:40 structural characterization 14:40 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 2 43 theme Gal 786:788 arg1 alpha 807:811 alpha 2-6 807:815 alpha 2-6 807:815 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 43 theme Gal 786:788 arg1 [NeuAc 800:805 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc 767:805 [NeuAc 800:805 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 44 theme alpha 671:675 arg1 GlcNAc 695:700 NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc 665:700 NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc 665:700 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 45 theme oxidation 484:492 arg1 chromatography 366:379 gas-liquid chromatography 355:379 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation 355:492 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 46 theme beta 726:729 arg1 alpha 744:748 alpha 2-6 744:752 alpha 2-6 744:752 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 46 theme beta 726:729 arg1 [Neu-Ac 736:742 NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac 706:742 NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6) 706:753 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 6 47 theme discovery 1294:1302 arg1 view 1275:1278 view 1275:1278 view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides 1275:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 1 48 attach isolated 198:205 arg2 sialylglycopeptide 169:186 a sialylglycopeptide 167:186 a sialylglycopeptide 167:186 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 1 48 attach isolated 198:205 arg1 urine 225:229 normal human urine 212:229 normal human urine 212:229 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 1 48 attach isolated 198:205 arg2 sialyloligosaccharides 140:161 Five major sialyloligosaccharides 129:161 Five major sialyloligosaccharides 129:161 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 4 49 gly glycoproteins 979:991 arg1 glycoproteins 979:991 glycoproteins 979:991 glycoproteins 979:991 The presence of compound 5 in urine may suggest that it derives from glycoproteins through a catabolic pathway involving cleavage of the carbohydrate-peptide linkage by an endo-N-acetylgalactosaminidase. 6628386 1 50 theme charcoal 234:241 arg1 filtration 259:268 gel filtration 255:268 gel filtration 255:268 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 1 50 theme charcoal 234:241 arg1 chromatography 284:297 ion-exchange chromatography 271:297 ion-exchange chromatography 271:297 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 1 50 theme charcoal 234:241 arg1 chromatography 310:323 paper chromatography 304:323 paper chromatography 304:323 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 1 50 theme charcoal 234:241 arg1 adsorption 243:252 charcoal adsorption 234:252 charcoal adsorption 234:252 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 2 51 dep GalNAc 755:760 arg1 Glc 580:582 NeuAc(alpha 2-6)Gal(beta 1-4)Glc 551:582 NeuAc(alpha 2-6)Gal(beta 1-4)Glc 551:582 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 52 theme beta 571:574 arg1 Glc 580:582 NeuAc(alpha 2-6)Gal(beta 1-4)Glc 551:582 NeuAc(alpha 2-6)Gal(beta 1-4)Glc 551:582 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 6 53 theme alpha 1382:1386 arg1 galactosides 1392:1403 sialyl(alpha 2-3)galactosides 1375:1403 sialyl(alpha 2-3)galactosides 1375:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 6 54 with strains 1338:1344 arg1 specificity 1359:1369 binding specificity 1351:1369 binding specificity for sialyl(alpha 2-3)galactosides 1351:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 6 55 theme alpha 1238:1242 arg1 linkage 1249:1255 the sialyl(alpha 2-3) linkage 1227:1255 the sialyl(alpha 2-3) linkage 1227:1255 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 0 56 theme sialyloligosaccharides 56:77 arg1 sialylglycopeptide 85:102 a sialylglycopeptide 83:102 a sialylglycopeptide from normal human urine 83:126 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 0 56 theme sialyloligosaccharides 56:77 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 0 56 theme sialyloligosaccharides 56:77 arg1 characterization 25:40 structural characterization 14:40 structural characterization 14:40 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 1 57 gly sialylglycopeptide 169:186 arg2 sialylglycopeptide 169:186 a sialylglycopeptide 167:186 a sialylglycopeptide 167:186 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 2 58 theme alpha 776:780 arg1 alpha 807:811 alpha 2-6 807:815 alpha 2-6 807:815 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 58 theme alpha 776:780 arg1 [NeuAc 800:805 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc 767:805 [NeuAc 800:805 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 59 theme Gal 644:646 arg1 Glc 657:659 NeuAc(alpha 2-3)Gal(beta 1-4)Glc 628:659 NeuAc(alpha 2-3)Gal(beta 1-4)Glc 628:659 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 60 theme disaccharide 403:414 arg1 derivatives 416:426 disaccharide derivatives 403:426 disaccharide derivatives 403:426 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 0 61 theme major 50:54 arg1 sialyloligosaccharides 56:77 five major sialyloligosaccharides 45:77 five major sialyloligosaccharides 45:77 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 4 62 theme compound 926:933 arg1 presence 914:921 The presence 910:921 The presence of compound 5 in urine 910:944 The presence of compound 5 in urine may suggest that it derives from glycoproteins through a catabolic pathway involving cleavage of the carbohydrate-peptide linkage by an endo-N-acetylgalactosaminidase. 6628386 1 63 theme major 134:138 arg1 sialyloligosaccharides 140:161 Five major sialyloligosaccharides 129:161 Five major sialyloligosaccharides 129:161 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 6 64 with compounds 1212:1220 arg1 linkage 1249:1255 the sialyl(alpha 2-3) linkage 1227:1255 the sialyl(alpha 2-3) linkage 1227:1255 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 0 65 from urine 122:126 arg1 sialylglycopeptide 85:102 a sialylglycopeptide 83:102 a sialylglycopeptide from normal human urine 83:126 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 0 65 from urine 122:126 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 0 65 from urine 122:126 arg1 characterization 25:40 structural characterization 14:40 structural characterization 14:40 Isolation and structural characterization of five major sialyloligosaccharides and a sialylglycopeptide from normal human urine. 6628386 6 66 from interest 1263:1270 arg1 view 1275:1278 view 1275:1278 view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides 1275:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 2 67 theme monosaccharide 384:397 arg1 chromatography 366:379 gas-liquid chromatography 355:379 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation 355:492 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 68 theme beta 685:688 arg1 GlcNAc 695:700 NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc 665:700 NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc 665:700 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 69 theme alpha 712:716 arg1 alpha 744:748 alpha 2-6 744:752 alpha 2-6 744:752 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 69 theme alpha 712:716 arg1 [Neu-Ac 736:742 NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac 706:742 NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6) 706:753 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 70 theme beta 790:793 arg1 alpha 807:811 alpha 2-6 807:815 alpha 2-6 807:815 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 70 theme beta 790:793 arg1 [NeuAc 800:805 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc 767:805 [NeuAc 800:805 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 4 71 from presence 914:921 arg1 urine 940:944 urine 940:944 urine 940:944 The presence of compound 5 in urine may suggest that it derives from glycoproteins through a catabolic pathway involving cleavage of the carbohydrate-peptide linkage by an endo-N-acetylgalactosaminidase. 6628386 1 72 theme gel 255:257 arg1 filtration 259:268 gel filtration 255:268 gel filtration 255:268 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 1 72 theme gel 255:257 arg1 adsorption 243:252 charcoal adsorption 234:252 charcoal adsorption 234:252 Five major sialyloligosaccharides and a sialylglycopeptide have been isolated from normal human urine by charcoal adsorption, gel filtration, ion-exchange chromatography, and paper chromatography. 6628386 2 73 theme alpha 557:561 arg1 Glc 580:582 NeuAc(alpha 2-6)Gal(beta 1-4)Glc 551:582 NeuAc(alpha 2-6)Gal(beta 1-4)Glc 551:582 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 6 74 theme uropathogenic 1307:1319 arg1 strains 1338:1344 uropathogenic Escherichia coli strains 1307:1344 uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides 1307:1403 The predominance of the compounds with the sialyl(alpha 2-3) linkage is of interest in view of the recent discovery of uropathogenic Escherichia coli strains with binding specificity for sialyl(alpha 2-3)galactosides. 6628386 2 75 theme analysis 441:448 arg1 chromatography 366:379 gas-liquid chromatography 355:379 gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation 355:492 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 76 theme Gal 681:683 arg1 GlcNAc 695:700 NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc 665:700 NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc 665:700 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 77 theme NeuAc 706:710 arg1 alpha 744:748 alpha 2-6 744:752 alpha 2-6 744:752 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 77 theme NeuAc 706:710 arg1 [Neu-Ac 736:742 NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac 706:742 NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6) 706:753 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 4 78 attach presence 914:921 arg1 urine 940:944 urine 940:944 urine 940:944 The presence of compound 5 in urine may suggest that it derives from glycoproteins through a catabolic pathway involving cleavage of the carbohydrate-peptide linkage by an endo-N-acetylgalactosaminidase. 6628386 4 78 attach presence 914:921 arg2 compound 926:933 compound 5 926:935 compound 5 926:935 The presence of compound 5 in urine may suggest that it derives from glycoproteins through a catabolic pathway involving cleavage of the carbohydrate-peptide linkage by an endo-N-acetylgalactosaminidase. 6628386 2 79 theme methylation 429:439 arg1 analysis 441:448 methylation analysis 429:448 methylation analysis 429:448 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 80 dep structures 518:527 arg1 1-O 832:834 1-O 832:834 1-O 832:834 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 6628386 2 81 theme Gal 567:569 arg1 Glc 580:582 NeuAc(alpha 2-6)Gal(beta 1-4)Glc 551:582 NeuAc(alpha 2-6)Gal(beta 1-4)Glc 551:582 Structural studies including gas-liquid chromatography of monosaccharide and disaccharide derivatives, methylation analysis, glycosidase treatments, and CrO3 oxidation indicated the following structures for the compounds: 1, NeuAc(alpha 2-6)Gal(beta 1-4)Glc; 2, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc; 3, NeuAc(alpha 2-3)Gal(beta 1-4)Glc; 4, NeuAc(alpha 2-3)Gal(beta 1-4) GlcNAc; 5, NeuAc(alpha 2-3)Gal(beta 1-3) [Neu-Ac(alpha 2-6)]GalNAc; and 6, NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]GalNAc (alpha 1-O)Ser. 3345750 0 0 theme patient 96:102 arg1 glycoproteins 77:89 respiratory-mucus glycoproteins 59:89 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 59:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 0 1 theme sugar 209:213 arg1 analysis 215:222 quantitative sugar analysis 196:222 quantitative sugar analysis 196:222 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 3 2 theme respiratory 443:453 arg1 mucins 455:460 respiratory mucins 443:460 respiratory mucins of a patient suffering from bronchiectasis 443:503 A pool of neutral carbohydrate chains was prepared from respiratory mucins of a patient suffering from bronchiectasis. 3345750 10 3 theme Fuc 1548:1550 arg1 alpha 1552:1556 Fuc alpha 1548:1556 Fuc alpha(1----3) 1548:1564 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 10 3 theme Fuc 1548:1550 arg1 1----3 1558:1563 1----3 1558:1563 1----3 1558:1563 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 0 4 theme quantitative 196:207 arg1 analysis 215:222 quantitative sugar analysis 196:222 quantitative sugar analysis 196:222 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 10 5 dep backbone-type 1444:1456 arg1 see 1508:1510 see 1508:1510 see text 1508:1515 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 10 6 theme Y 1388:1388 arg1 determinant 1390:1400 the Y determinant 1384:1400 the Y determinant 1384:1400 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 6 7 from J.F.G. 1143:1148 arg1 present 1001:1007 present 1001:1007 present 1001:1007 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 10 8 theme structures 1478:1487 arg1 determinant 1422:1432 the H determinant 1416:1432 the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b 1416:1524 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 0 9 gly glycoproteins 77:89 arg1 glycoproteins 77:89 respiratory-mucus glycoproteins 59:89 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 59:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 9 10 theme new 1211:1213 arg1 ten 1203:1205 ten 1203:1205 ten 1203:1205 The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. 3345750 9 10 theme new 1211:1213 arg1 structures 1215:1224 new structures 1211:1224 new structures isolated from bronchial mucins 1211:1255 The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. 3345750 4 11 theme smaller-size 538:549 arg1 oligosaccharide-alditols 551:574 35 smaller-size oligosaccharide-alditols 535:574 35 smaller-size oligosaccharide-alditols 535:574 Fractionation by HPLC led to 35 smaller-size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). 3345750 9 12 attach isolated 1226:1233 arg2 ten 1203:1205 ten 1203:1205 ten 1203:1205 The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. 3345750 9 12 attach isolated 1226:1233 arg2 structures 1215:1224 new structures 1211:1224 new structures isolated from bronchial mucins 1211:1255 The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. 3345750 9 12 attach isolated 1226:1233 arg1 mucins 1250:1255 bronchial mucins 1240:1255 bronchial mucins 1240:1255 The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. 3345750 0 13 theme analysis 215:222 arg1 combination 149:159 combination 149:159 combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis 149:222 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 10 14 theme backbone-type 1444:1456 arg1 determinant 1422:1432 the H determinant 1416:1432 the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b 1416:1524 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 2 15 theme GalNAc-ol 291:299 arg1 core 301:304 the GlcNAc beta(1----3)GalNAc-ol core 268:304 the GlcNAc beta(1----3)GalNAc-ol core (type 3) 268:313 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 15 theme GalNAc-ol 291:299 arg1 type 307:310 type 3 307:312 type 3 307:312 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 10 16 dep see 1508:1510 arg1 Formula 1499:1505 Formula 1499:1505 Formula 1499:1505 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 4 17 theme core 627:630 arg1 type 632:635 core type 1 627:637 core type 1 627:637 Fractionation by HPLC led to 35 smaller-size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). 3345750 9 18 theme oligosaccharides 1310:1325 arg1 they 1258:1261 they 1258:1261 they 1258:1261 The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. 3345750 9 18 theme oligosaccharides 1310:1325 arg1 extensions 1271:1280 all extensions 1267:1280 all extensions of the above-mentioned nine oligosaccharides 1267:1325 The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. 3345750 0 19 attach derived 46:52 arg1 glycoproteins 77:89 respiratory-mucus glycoproteins 59:89 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 59:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 0 19 attach derived 46:52 arg2 oligosaccharides 29:44 neutral oligosaccharides 21:44 neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 21:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 6 20 theme structures 913:922 arg1 10b 937:939 1, 5, 9, 6, 10b, 13, 19, 15b and 18.1 925:961 10b 937:939 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 20 theme structures 913:922 arg1 Nine 901:904 Nine 901:904 Nine 901:904 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 20 theme structures 913:922 arg1 15b 950:952 15b 950:952 15b 950:952 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 20 theme structures 913:922 arg1 18.1 958:961 18.1 958:961 18.1 958:961 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 20 theme structures 913:922 arg1 13 942:943 13 942:943 13 942:943 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 20 theme structures 913:922 arg1 structures 913:922 the structures 909:922 the structures 909:922 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 20 theme structures 913:922 arg1 19 946:947 19 946:947 19 946:947 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 0 21 theme Primary 0:6 arg1 structure 8:16 Primary structure 0:16 Primary structure 0:16 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 10 22 contain containing 1373:1382 arg1 octassaccharide-alditols 1348:1371 octassaccharide-alditols 1348:1371 octassaccharide-alditols containing the Y determinant 1348:1400 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 10 22 contain containing 1373:1382 arg1 compounds 1334:1342 These compounds 1328:1342 These compounds 1328:1342 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 10 22 contain containing 1373:1382 arg2 determinant 1390:1400 the Y determinant 1384:1400 the Y determinant 1384:1400 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 4 23 theme A. 678:679 arg1 paper 783:787 Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper 671:787 Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal 671:803 Fractionation by HPLC led to 35 smaller-size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). 3345750 5 24 dep types 886:890 arg1 4 898:898 4 898:898 4 898:898 In this second part, we identified 19 oligosaccharide-alditols possessing core types 3 and 4. 3345750 5 24 dep types 886:890 arg1 3 892:892 3 892:892 3 892:892 In this second part, we identified 19 oligosaccharide-alditols possessing core types 3 and 4. 3345750 0 25 theme neutral 21:27 arg1 oligosaccharides 29:44 neutral oligosaccharides 21:44 neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 21:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 10 26 dep octassaccharide-alditols 1348:1371 arg1 23c 1536:1538 23c 1536:1538 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch 1536:1667 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 9 27 theme bronchial 1240:1248 arg1 mucins 1250:1255 bronchial mucins 1240:1255 bronchial mucins 1240:1255 The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. 3345750 5 28 theme core 881:884 arg1 types 886:890 core types 3 and 4 881:898 core types 3 and 4 881:898 In this second part, we identified 19 oligosaccharide-alditols possessing core types 3 and 4. 3345750 3 29 theme neutral 397:403 arg1 chains 418:423 neutral carbohydrate chains 397:423 neutral carbohydrate chains 397:423 A pool of neutral carbohydrate chains was prepared from respiratory mucins of a patient suffering from bronchiectasis. 3345750 3 30 theme patient 467:473 arg1 mucins 455:460 respiratory mucins 443:460 respiratory mucins of a patient suffering from bronchiectasis 443:503 A pool of neutral carbohydrate chains was prepared from respiratory mucins of a patient suffering from bronchiectasis. 3345750 10 31 theme 21b 1522:1524 arg1 determinant 1422:1432 the H determinant 1416:1432 the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b 1416:1524 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 4 32 dep established 658:668 arg1 paper 783:787 Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper 671:787 Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal 671:803 Fractionation by HPLC led to 35 smaller-size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). 3345750 3 33 theme carbohydrate 405:416 arg1 chains 418:423 neutral carbohydrate chains 397:423 neutral carbohydrate chains 397:423 A pool of neutral carbohydrate chains was prepared from respiratory mucins of a patient suffering from bronchiectasis. 3345750 4 34 with structure 581:589 arg1 type 632:635 core type 1 627:637 core type 1 627:637 Fractionation by HPLC led to 35 smaller-size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). 3345750 4 34 with structure 581:589 arg1 type 642:645 type 2 642:647 type 2 642:647 Fractionation by HPLC led to 35 smaller-size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). 3345750 0 35 theme oligosaccharides 29:44 arg1 structure 8:16 Primary structure 0:16 Primary structure 0:16 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 10 36 from 23c 1637:1639 arg1 3-branch 1660:1667 the 3-branch 1656:1667 the 3-branch 1656:1667 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 2 37 theme GalNAc-ol 362:370 arg1 core 372:375 the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core 318:375 the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4) 318:384 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 37 theme GalNAc-ol 362:370 arg1 type 378:381 type 4 378:383 type 4 378:383 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 0 38 theme respiratory-mucus 59:75 arg1 glycoproteins 77:89 respiratory-mucus glycoproteins 59:89 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 59:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 6 39 attach present 1001:1007 arg1 A. 1058:1059 A. 1058:1059 A. 1058:1059 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 J.F.G. 1143:1148 J.F.G. 1143:1148 J.F.G. 1143:1148 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 M. 1073:1074 M. 1073:1074 M. 1073:1074 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 Mutsaers 1090:1097 Mutsaers 1090:1097 Mutsaers 1090:1097 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg2 13 942:943 13 942:943 13 942:943 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 J.G.H. 1100:1105 J.G.H. 1100:1105 J.G.H. 1100:1105 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 Boersma 1049:1055 Boersma 1049:1055 Boersma 1049:1055 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg2 19 946:947 19 946:947 19 946:947 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg2 structures 913:922 the structures 909:922 the structures 909:922 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 Roussel 1077:1083 Roussel 1077:1083 Roussel 1077:1083 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg2 10b 937:939 1, 5, 9, 6, 10b, 13, 19, 15b and 18.1 925:961 10b 937:939 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 P. 1086:1087 P. 1086:1087 P. 1086:1087 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg2 15b 950:952 15b 950:952 15b 950:952 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 H. 1124:1125 H. 1124:1125 H. 1124:1125 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 Eur 1157:1159 Eur 1157:1159 Eur 1157:1159 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg2 18.1 958:961 18.1 958:961 18.1 958:961 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 Van 1111:1113 Van 1111:1113 Van 1111:1113 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg1 Lhermitte 1062:1070 Lhermitte 1062:1070 Lhermitte 1062:1070 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 39 attach present 1001:1007 arg2 Nine 901:904 Nine 901:904 Nine 901:904 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 0 40 theme 1H-NMR 172:177 arg1 spectroscopy 179:190 500-MHz 1H-NMR spectroscopy 164:190 500-MHz 1H-NMR spectroscopy 164:190 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 4 41 from paper 783:787 arg1 journal 797:803 this journal 792:803 this journal 792:803 Fractionation by HPLC led to 35 smaller-size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). 3345750 2 42 theme oligosaccharides 244:259 arg1 Structure 228:236 Structure 228:236 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 228:385 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 6 43 dep J.F.G. 1143:1148 arg1 G. 1045:1046 G. 1045:1046 G. 1045:1046 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 0 44 theme 500-MHz 164:170 arg1 spectroscopy 179:190 500-MHz 1H-NMR spectroscopy 164:190 500-MHz 1H-NMR spectroscopy 164:190 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 10 45 theme partial 1470:1476 arg1 structures 1478:1487 partial structures 1470:1487 partial structures thereof 1470:1495 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 2 46 theme beta 329:332 arg1 core 372:375 the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core 318:375 the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4) 318:384 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 46 theme beta 329:332 arg1 type 378:381 type 4 378:383 type 4 378:383 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 9 47 theme above-mentioned 1289:1303 arg1 oligosaccharides 1310:1325 the above-mentioned nine oligosaccharides 1285:1325 the above-mentioned nine oligosaccharides 1285:1325 The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. 3345750 4 48 theme preceding 773:781 arg1 paper 783:787 Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper 671:787 Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal 671:803 Fractionation by HPLC led to 35 smaller-size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). 3345750 2 49 theme GlcNAc 322:327 arg1 beta 329:332 GlcNAc beta 322:332 the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4) 318:384 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 49 theme GlcNAc 322:327 arg1 beta 349:352 1----3)[GlcNAc beta(1----6) 334:360 1----3)[GlcNAc beta(1----6) 334:360 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 10 50 theme 2 1463:1463 arg1 determinant 1422:1432 the H determinant 1416:1432 the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b 1416:1524 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 0 51 theme spectroscopy 179:190 arg1 combination 149:159 combination 149:159 combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis 149:222 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345750 5 52 theme second 815:820 arg1 part 822:825 this second part 810:825 this second part 810:825 In this second part, we identified 19 oligosaccharide-alditols possessing core types 3 and 4. 3345750 10 53 theme H 1420:1420 arg1 determinant 1422:1432 the H determinant 1416:1432 the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b 1416:1524 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 6 54 from present 1001:1007 arg1 J.F.G. 1143:1148 J.F.G. 1143:1148 J.F.G. 1143:1148 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 M. 1073:1074 M. 1073:1074 M. 1073:1074 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 Mutsaers 1090:1097 Mutsaers 1090:1097 Mutsaers 1090:1097 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 Boersma 1049:1055 Boersma 1049:1055 Boersma 1049:1055 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 J.G.H. 1100:1105 J.G.H. 1100:1105 J.G.H. 1100:1105 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 H. 1124:1125 H. 1124:1125 H. 1124:1125 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 A. 1058:1059 A. 1058:1059 A. 1058:1059 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 Roussel 1077:1083 Roussel 1077:1083 Roussel 1077:1083 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 Eur 1157:1159 Eur 1157:1159 Eur 1157:1159 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 P. 1086:1087 P. 1086:1087 P. 1086:1087 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 Van 1111:1113 Van 1111:1113 Van 1111:1113 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 54 from present 1001:1007 arg1 Lhermitte 1062:1070 Lhermitte 1062:1070 Lhermitte 1062:1070 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 3 55 theme chains 418:423 arg1 pool 389:392 A pool 387:392 A pool of neutral carbohydrate chains 387:423 A pool of neutral carbohydrate chains was prepared from respiratory mucins of a patient suffering from bronchiectasis. 3345750 4 56 theme oligosaccharide-alditols 597:620 arg1 structure 581:589 the structure 577:589 the structure of 16 oligosaccharide-alditols with core type 1 or type 2 577:647 Fractionation by HPLC led to 35 smaller-size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). 3345750 2 57 theme beta 279:282 arg1 core 301:304 the GlcNAc beta(1----3)GalNAc-ol core 268:304 the GlcNAc beta(1----3)GalNAc-ol core (type 3) 268:313 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 57 theme beta 279:282 arg1 type 307:310 type 3 307:312 type 3 307:312 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 10 58 from Fuc 1598:1600 arg1 6-branch 1609:1616 the 6-branch 1605:1616 the 6-branch 1605:1616 These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. 3345750 2 59 contain having 261:266 arg2 type 378:381 type 4 378:383 type 4 378:383 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 59 contain having 261:266 arg2 core 372:375 the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core 318:375 the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4) 318:384 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 59 contain having 261:266 arg2 type 307:310 type 3 307:312 type 3 307:312 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 59 contain having 261:266 arg1 oligosaccharides 244:259 19 oligosaccharides 241:259 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4) 241:384 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 59 contain having 261:266 arg2 core 301:304 the GlcNAc beta(1----3)GalNAc-ol core 268:304 the GlcNAc beta(1----3)GalNAc-ol core (type 3) 268:313 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 60 theme GlcNAc 272:277 arg1 beta 279:282 GlcNAc beta 272:282 the GlcNAc beta(1----3)GalNAc-ol core (type 3) 268:313 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 60 theme GlcNAc 272:277 arg1 1----3 284:289 1----3 284:289 1----3 284:289 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 61 theme [GlcNAc 341:347 arg1 beta 329:332 GlcNAc beta 322:332 the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4) 318:384 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 2 61 theme [GlcNAc 341:347 arg1 beta 349:352 1----3)[GlcNAc beta(1----6) 334:360 1----3)[GlcNAc beta(1----6) 334:360 Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). 3345750 5 62 contain possessing 870:879 arg1 oligosaccharide-alditols 845:868 19 oligosaccharide-alditols 842:868 19 oligosaccharide-alditols possessing core types 3 and 4 842:898 In this second part, we identified 19 oligosaccharide-alditols possessing core types 3 and 4. 3345750 5 62 contain possessing 870:879 arg2 types 886:890 core types 3 and 4 881:898 core types 3 and 4 881:898 In this second part, we identified 19 oligosaccharide-alditols possessing core types 3 and 4. 3345750 6 63 located present 1001:1007 arg1 A. 1058:1059 A. 1058:1059 A. 1058:1059 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 J.F.G. 1143:1148 J.F.G. 1143:1148 J.F.G. 1143:1148 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 M. 1073:1074 M. 1073:1074 M. 1073:1074 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 Mutsaers 1090:1097 Mutsaers 1090:1097 Mutsaers 1090:1097 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg2 13 942:943 13 942:943 13 942:943 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 J.G.H. 1100:1105 J.G.H. 1100:1105 J.G.H. 1100:1105 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 Boersma 1049:1055 Boersma 1049:1055 Boersma 1049:1055 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg2 19 946:947 19 946:947 19 946:947 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg2 structures 913:922 the structures 909:922 the structures 909:922 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 Roussel 1077:1083 Roussel 1077:1083 Roussel 1077:1083 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg2 10b 937:939 1, 5, 9, 6, 10b, 13, 19, 15b and 18.1 925:961 10b 937:939 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 P. 1086:1087 P. 1086:1087 P. 1086:1087 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg2 15b 950:952 15b 950:952 15b 950:952 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 H. 1124:1125 H. 1124:1125 H. 1124:1125 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 Eur 1157:1159 Eur 1157:1159 Eur 1157:1159 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg2 18.1 958:961 18.1 958:961 18.1 958:961 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 Van 1111:1113 Van 1111:1113 Van 1111:1113 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg1 Lhermitte 1062:1070 Lhermitte 1062:1070 Lhermitte 1062:1070 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 3345750 6 63 located present 1001:1007 arg2 Nine 901:904 Nine 901:904 Nine 901:904 Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. 7679920 5 0 contain contained 1122:1130 arg2 chain 1165:1169 a fucosylated triantennary sugar chain 1132:1169 a fucosylated triantennary sugar chain 1132:1169 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 0 contain contained 1122:1130 arg2 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 0 contain contained 1122:1130 arg2 component 1182:1190 a major component 1174:1190 a major component 1174:1190 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 0 contain contained 1122:1130 arg1 species 1114:1120 The Con A-nonreactive and LCA-nonreactive species 1072:1120 The Con A-nonreactive and LCA-nonreactive species 1072:1120 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 1 1 theme exoglycosidase 409:422 arg1 digestion 424:432 stepwise exoglycosidase digestion 400:432 stepwise exoglycosidase digestion 400:432 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 3 2 with one 772:774 arg1 residue 790:796 a fucose residue 781:796 a fucose residue at the innermost N-acetylglucosamine residue 781:841 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 1 3 theme Concanavalin 277:288 arg1 A 290:290 Concanavalin A 277:290 Concanavalin A (Con A) 277:298 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 1 3 theme Concanavalin 277:288 arg1 A 297:297 Con A 293:297 Con A 293:297 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 4 4 theme trimannosyl 984:994 arg1 core 996:999 the trimannosyl core 980:999 the trimannosyl core 980:999 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 6 5 gly fucosylated 1356:1366 arg1 chains 1407:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 Thus, the fucosylated and non-fucosylated triantennary sugar chains were newly identified in human AFP. 7679920 6 6 theme triantennary 1388:1399 arg1 chains 1407:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 Thus, the fucosylated and non-fucosylated triantennary sugar chains were newly identified in human AFP. 7679920 5 7 gly fucosylated 1134:1144 arg1 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 7 gly fucosylated 1134:1144 arg1 component 1182:1190 a major component 1174:1190 a major component 1174:1190 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 7 gly fucosylated 1134:1144 arg1 chain 1165:1169 a fucosylated triantennary sugar chain 1132:1169 a fucosylated triantennary sugar chain 1132:1169 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 4 8 theme bisecting-N-acetylglucosamine 939:967 arg1 residue 969:975 a bisecting-N-acetylglucosamine residue 937:975 a bisecting-N-acetylglucosamine residue at the trimannosyl core 937:999 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 3 9 contain had 754:756 arg1 species 746:752 the Con A-reactive and LCA-reactive species 710:752 the Con A-reactive and LCA-reactive species 710:752 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 3 9 contain had 754:756 arg2 one 772:774 a biantennary one 758:774 a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue 758:841 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 3 10 theme N-acetylglucosamine 815:833 arg1 residue 835:841 the innermost N-acetylglucosamine residue 801:841 the innermost N-acetylglucosamine residue 801:841 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 8 11 from chains 1720:1725 arg1 patients 1739:1746 patients 1739:1746 patients with neoplastic diseases of the liver 1739:1784 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 8 12 with patients 1739:1746 arg1 diseases 1764:1771 neoplastic diseases 1753:1771 neoplastic diseases of the liver 1753:1784 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 1 13 theme human 211:215 arg1 AFP 236:238 AFP 236:238 AFP 236:238 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 1 13 theme human 211:215 arg1 alpha-fetoprotein 217:233 human alpha-fetoprotein 211:233 various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) 203:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 0 14 theme triantennary 138:149 arg1 glycans 151:157 fucosylated and non-fucosylated triantennary glycans 106:157 fucosylated and non-fucosylated triantennary glycans 106:157 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 1 15 theme oligosaccharides 379:394 arg1 pyridylamination 353:368 pyridylamination 353:368 pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion 353:432 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 6 16 theme fucosylated 1356:1366 arg1 chains 1407:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 Thus, the fucosylated and non-fucosylated triantennary sugar chains were newly identified in human AFP. 7679920 5 17 theme trimannosyl 1328:1338 arg1 core 1340:1343 the trimannosyl core 1324:1343 the trimannosyl core 1324:1343 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 1 18 theme stepwise 400:407 arg1 digestion 424:432 stepwise exoglycosidase digestion 400:432 stepwise exoglycosidase digestion 400:432 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 3 19 with patients 630:637 arg1 carcinoma 659:667 hepatocellular carcinoma 644:667 hepatocellular carcinoma 644:667 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 1 20 theme digestion 424:432 arg1 pyridylamination 353:368 pyridylamination 353:368 pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion 353:432 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 8 21 from patients 1739:1746 arg1 AFP 1730:1732 AFP 1730:1732 AFP from patients with neoplastic diseases of the liver 1730:1784 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 8 21 from patients 1739:1746 arg1 chains 1720:1725 the carbohydrate chains 1703:1725 the carbohydrate chains of AFP from patients with neoplastic diseases of the liver 1703:1784 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 5 22 theme major 1176:1180 arg1 component 1182:1190 a major component 1174:1190 a major component 1174:1190 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 22 theme major 1176:1180 arg1 chain 1165:1169 a fucosylated triantennary sugar chain 1132:1169 a fucosylated triantennary sugar chain 1132:1169 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 1 23 theme Chemical 160:167 arg1 structures 169:178 Chemical structures 160:178 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) 160:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 0 24 theme hepatocellular 68:81 arg1 carcinoma 83:91 hepatocellular carcinoma 68:91 hepatocellular carcinoma 68:91 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 5 25 theme sugar 1234:1238 arg1 chain 1240:1244 a triantennary sugar chain 1219:1244 a triantennary sugar chain 1219:1244 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 25 theme sugar 1234:1238 arg1 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 3 26 theme sugar 693:697 arg1 chain 699:703 a biantennary sugar chain 679:703 a biantennary sugar chain 679:703 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 1 27 theme sugar 187:191 arg1 chains 193:198 the sugar chains 183:198 the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) 183:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 4 28 theme N-acetylglucosamine 1043:1061 arg1 residue 1063:1069 the innermost N-acetylglucosamine residue 1029:1069 the innermost N-acetylglucosamine residue 1029:1069 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 0 29 gly non-fucosylated 122:136 arg1 glycans 151:157 fucosylated and non-fucosylated triantennary glycans 106:157 fucosylated and non-fucosylated triantennary glycans 106:157 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 7 30 with patient 1511:1517 arg1 carcinoma 1536:1544 gallbladder carcinoma 1524:1544 gallbladder carcinoma which metastasizes to the liver 1524:1576 Essentially identical results were obtained for AFP from the patient with gallbladder carcinoma which metastasizes to the liver. 7679920 6 31 gly non-fucosylated 1372:1386 arg1 chains 1407:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 Thus, the fucosylated and non-fucosylated triantennary sugar chains were newly identified in human AFP. 7679920 4 32 theme A-nonreactive 852:864 arg1 species 883:889 The Con A-nonreactive and LCA-reactive species 844:889 The Con A-nonreactive and LCA-reactive species 844:889 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 8 33 theme liver 1780:1784 arg1 diseases 1764:1771 neoplastic diseases 1753:1771 neoplastic diseases of the liver 1753:1784 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 2 34 theme performance 484:494 arg1 chromatography 503:516 high performance liquid chromatography 479:516 high performance liquid chromatography 479:516 Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. 7679920 0 35 theme Carbohydrate 0:11 arg1 structures 13:22 Carbohydrate structures 0:22 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 0:158 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 1 36 theme Con 293:295 arg1 A 290:290 Concanavalin A 277:290 Concanavalin A (Con A) 277:298 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 1 36 theme Con 293:295 arg1 A 297:297 Con A 293:297 Con A 293:297 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 0 37 gly fucosylated 106:116 arg1 glycans 151:157 fucosylated and non-fucosylated triantennary glycans 106:157 fucosylated and non-fucosylated triantennary glycans 106:157 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 7 38 theme identical 1462:1470 arg1 results 1472:1478 Essentially identical results 1450:1478 Essentially identical results 1450:1478 Essentially identical results were obtained for AFP from the patient with gallbladder carcinoma which metastasizes to the liver. 7679920 2 39 theme size-fractionation 460:477 arg1 systems 518:524 reversed-phase and size-fractionation high performance liquid chromatography systems 441:524 reversed-phase and size-fractionation high performance liquid chromatography systems 441:524 Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. 7679920 2 40 theme reversed-phase 441:454 arg1 systems 518:524 reversed-phase and size-fractionation high performance liquid chromatography systems 441:524 reversed-phase and size-fractionation high performance liquid chromatography systems 441:524 Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. 7679920 3 41 dep A-reactive 579:588 arg1 The 571:573 The 571:573 The 571:573 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 3 42 theme A-reactive 718:727 arg1 species 746:752 the Con A-reactive and LCA-reactive species 710:752 the Con A-reactive and LCA-reactive species 710:752 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 4 43 theme biantennary 903:913 arg1 chain 921:925 a biantennary sugar chain 901:925 a biantennary sugar chain 901:925 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 4 44 from residue 1063:1069 arg1 residue 1018:1024 a focus residue 1010:1024 a focus residue at the innermost N-acetylglucosamine residue 1010:1069 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 0 45 theme alpha-fetoprotein 33:49 arg1 structures 13:22 Carbohydrate structures 0:22 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 0:158 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 1 46 theme Lens 304:307 arg1 LCA 331:333 LCA 331:333 LCA 331:333 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 1 46 theme Lens 304:307 arg1 agglutinin 319:328 Lens culinaris agglutinin 304:328 Lens culinaris agglutinin (LCA) 304:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 5 47 theme triantennary 1146:1157 arg1 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 47 theme triantennary 1146:1157 arg1 component 1182:1190 a major component 1174:1190 a major component 1174:1190 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 47 theme triantennary 1146:1157 arg1 chain 1165:1169 a fucosylated triantennary sugar chain 1132:1169 a fucosylated triantennary sugar chain 1132:1169 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 48 theme biantennary 1252:1262 arg1 chain 1270:1274 a biantennary sugar chain 1250:1274 a biantennary sugar chain 1250:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 48 theme biantennary 1252:1262 arg1 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 2 49 dep reversed-phase 441:454 arg1 chromatography 503:516 high performance liquid chromatography 479:516 high performance liquid chromatography 479:516 Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. 7679920 0 50 theme patients 54:61 arg1 alpha-fetoprotein 33:49 human alpha-fetoprotein 27:49 human alpha-fetoprotein of patients with hepatocellular carcinoma 27:91 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 2 51 dep identified 529:538 arg1 Using 435:439 Using 435:439 Using reversed-phase and size-fractionation high performance liquid chromatography systems 435:524 Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. 7679920 8 52 theme AFP 1730:1732 arg1 chains 1720:1725 the carbohydrate chains 1703:1725 the carbohydrate chains of AFP from patients with neoplastic diseases of the liver 1703:1784 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 4 53 theme LCA-reactive 870:881 arg1 species 883:889 The Con A-nonreactive and LCA-reactive species 844:889 The Con A-nonreactive and LCA-reactive species 844:889 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 1 54 theme species 241:247 arg1 chains 193:198 the sugar chains 183:198 the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) 183:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 3 55 theme LCA-nonreactive 594:608 arg1 species 610:616 LCA-nonreactive species 594:616 LCA-nonreactive species 594:616 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 3 56 theme LCA-reactive 733:744 arg1 species 746:752 the Con A-reactive and LCA-reactive species 710:752 the Con A-reactive and LCA-reactive species 710:752 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 0 57 with patients 54:61 arg1 carcinoma 83:91 hepatocellular carcinoma 68:91 hepatocellular carcinoma 68:91 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 3 58 theme Con 575:577 arg1 A-reactive 579:588 Con A-reactive 575:588 Con A-reactive 575:588 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 1 59 theme different 254:262 arg1 affinity 264:271 different affinity 254:271 different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) 254:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 1 60 with species 241:247 arg1 affinity 264:271 different affinity 254:271 different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) 254:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 5 61 theme sugar 1264:1268 arg1 chain 1270:1274 a biantennary sugar chain 1250:1274 a biantennary sugar chain 1250:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 61 theme sugar 1264:1268 arg1 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 3 62 theme biantennary 760:770 arg1 one 772:774 a biantennary one 758:774 a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue 758:841 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 8 63 theme chains 1720:1725 arg1 feature 1692:1698 a characteristic feature 1675:1698 a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver 1675:1784 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 8 63 theme chains 1720:1725 arg1 increment 1611:1619 the increment 1607:1619 the increment in fucosylation and branching to form new antennae 1607:1670 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 3 64 contain contained 669:677 arg1 species 610:616 LCA-nonreactive species 594:616 LCA-nonreactive species 594:616 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 3 64 contain contained 669:677 arg2 chain 699:703 a biantennary sugar chain 679:703 a biantennary sugar chain 679:703 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 3 64 contain contained 669:677 arg1 A-reactive 579:588 Con A-reactive 575:588 Con A-reactive 575:588 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 6 65 theme sugar 1401:1405 arg1 chains 1407:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 Thus, the fucosylated and non-fucosylated triantennary sugar chains were newly identified in human AFP. 7679920 3 66 from A-reactive 579:588 arg1 patients 630:637 patients 630:637 patients with hepatocellular carcinoma 630:667 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 1 67 theme chains 193:198 arg1 structures 169:178 Chemical structures 160:178 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) 160:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 3 68 theme fucose 783:788 arg1 residue 790:796 a fucose residue 781:796 a fucose residue at the innermost N-acetylglucosamine residue 781:841 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 6 69 theme non-fucosylated 1372:1386 arg1 chains 1407:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 the fucosylated and non-fucosylated triantennary sugar chains 1352:1412 Thus, the fucosylated and non-fucosylated triantennary sugar chains were newly identified in human AFP. 7679920 1 70 theme various 203:209 arg1 species 241:247 various human alpha-fetoprotein (AFP) species 203:247 various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) 203:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 0 71 theme glycans 151:157 arg1 presence 94:101 presence 94:101 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 0:158 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 3 72 theme AFP 621:623 arg1 species 610:616 LCA-nonreactive species 594:616 LCA-nonreactive species 594:616 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 3 72 theme AFP 621:623 arg1 A-reactive 579:588 Con A-reactive 575:588 Con A-reactive 575:588 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 1 73 theme alpha-fetoprotein 217:233 arg1 species 241:247 various human alpha-fetoprotein (AFP) species 203:247 various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) 203:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 4 74 theme focus 1012:1016 arg1 residue 1018:1024 a focus residue 1010:1024 a focus residue at the innermost N-acetylglucosamine residue 1010:1069 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 3 75 theme innermost 805:813 arg1 residue 835:841 the innermost N-acetylglucosamine residue 801:841 the innermost N-acetylglucosamine residue 801:841 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 7 76 theme gallbladder 1524:1534 arg1 carcinoma 1536:1544 gallbladder carcinoma 1524:1544 gallbladder carcinoma which metastasizes to the liver 1524:1576 Essentially identical results were obtained for AFP from the patient with gallbladder carcinoma which metastasizes to the liver. 7679920 5 77 theme minor 1201:1205 arg1 chain 1270:1274 a biantennary sugar chain 1250:1274 a biantennary sugar chain 1250:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 77 theme minor 1201:1205 arg1 chain 1240:1244 a triantennary sugar chain 1219:1244 a triantennary sugar chain 1219:1244 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 77 theme minor 1201:1205 arg1 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 77 theme minor 1201:1205 arg1 chain 1165:1169 a fucosylated triantennary sugar chain 1132:1169 a fucosylated triantennary sugar chain 1132:1169 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 3 78 theme hepatocellular 644:657 arg1 carcinoma 659:667 hepatocellular carcinoma 644:667 hepatocellular carcinoma 644:667 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 5 79 from core 1340:1343 arg1 residue 1313:1319 a bisecting-N-acetylglucosamine residue 1281:1319 a bisecting-N-acetylglucosamine residue at the trimannosyl core 1281:1343 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 6 80 theme human 1439:1443 arg1 AFP 1445:1447 human AFP 1439:1447 human AFP 1439:1447 Thus, the fucosylated and non-fucosylated triantennary sugar chains were newly identified in human AFP. 7679920 3 81 from patients 630:637 arg1 species 610:616 LCA-nonreactive species 594:616 LCA-nonreactive species 594:616 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 3 81 from patients 630:637 arg1 AFP 621:623 AFP 621:623 AFP from patients with hepatocellular carcinoma 621:667 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 3 81 from patients 630:637 arg1 A-reactive 579:588 Con A-reactive 575:588 Con A-reactive 575:588 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 4 82 contain contained 891:899 arg1 species 883:889 The Con A-nonreactive and LCA-reactive species 844:889 The Con A-nonreactive and LCA-reactive species 844:889 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 4 82 contain contained 891:899 arg2 chain 921:925 a biantennary sugar chain 901:925 a biantennary sugar chain 901:925 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 4 83 from core 996:999 arg1 residue 969:975 a bisecting-N-acetylglucosamine residue 937:975 a bisecting-N-acetylglucosamine residue at the trimannosyl core 937:999 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 3 84 theme biantennary 681:691 arg1 chain 699:703 a biantennary sugar chain 679:703 a biantennary sugar chain 679:703 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 2 85 theme pyridylamino-sugar 544:561 arg1 chains 563:568 six pyridylamino-sugar chains 540:568 six pyridylamino-sugar chains 540:568 Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. 7679920 8 86 theme new 1659:1661 arg1 antennae 1663:1670 new antennae 1659:1670 new antennae 1659:1670 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 3 87 from species 610:616 arg1 patients 630:637 patients 630:637 patients with hepatocellular carcinoma 630:667 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 0 88 theme fucosylated 106:116 arg1 glycans 151:157 fucosylated and non-fucosylated triantennary glycans 106:157 fucosylated and non-fucosylated triantennary glycans 106:157 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 4 89 theme innermost 1033:1041 arg1 residue 1063:1069 the innermost N-acetylglucosamine residue 1029:1069 the innermost N-acetylglucosamine residue 1029:1069 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 0 90 theme non-fucosylated 122:136 arg1 glycans 151:157 fucosylated and non-fucosylated triantennary glycans 106:157 fucosylated and non-fucosylated triantennary glycans 106:157 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 5 91 theme A-nonreactive 1080:1092 arg1 species 1114:1120 The Con A-nonreactive and LCA-nonreactive species 1072:1120 The Con A-nonreactive and LCA-nonreactive species 1072:1120 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 8 92 theme characteristic 1677:1690 arg1 feature 1692:1698 a characteristic feature 1675:1698 a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver 1675:1784 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 8 92 theme characteristic 1677:1690 arg1 increment 1611:1619 the increment 1607:1619 the increment in fucosylation and branching to form new antennae 1607:1670 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 4 93 theme Con 848:850 arg1 species 883:889 The Con A-nonreactive and LCA-reactive species 844:889 The Con A-nonreactive and LCA-reactive species 844:889 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 5 94 theme triantennary 1221:1232 arg1 chain 1240:1244 a triantennary sugar chain 1219:1244 a triantennary sugar chain 1219:1244 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 94 theme triantennary 1221:1232 arg1 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 2 95 theme high 479:482 arg1 chromatography 503:516 high performance liquid chromatography 479:516 high performance liquid chromatography 479:516 Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. 7679920 3 96 from residue 835:841 arg1 residue 790:796 a fucose residue 781:796 a fucose residue at the innermost N-acetylglucosamine residue 781:841 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 0 97 theme human 27:31 arg1 alpha-fetoprotein 33:49 human alpha-fetoprotein 27:49 human alpha-fetoprotein of patients with hepatocellular carcinoma 27:91 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 5 98 theme bisecting-N-acetylglucosamine 1283:1311 arg1 residue 1313:1319 a bisecting-N-acetylglucosamine residue 1281:1319 a bisecting-N-acetylglucosamine residue at the trimannosyl core 1281:1343 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 8 99 theme carbohydrate 1707:1718 arg1 chains 1720:1725 the carbohydrate chains 1703:1725 the carbohydrate chains of AFP from patients with neoplastic diseases of the liver 1703:1784 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 3 100 theme Con 714:716 arg1 species 746:752 the Con A-reactive and LCA-reactive species 710:752 the Con A-reactive and LCA-reactive species 710:752 The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. 7679920 5 101 theme fucosylated 1134:1144 arg1 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 101 theme fucosylated 1134:1144 arg1 component 1182:1190 a major component 1174:1190 a major component 1174:1190 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 101 theme fucosylated 1134:1144 arg1 chain 1165:1169 a fucosylated triantennary sugar chain 1132:1169 a fucosylated triantennary sugar chain 1132:1169 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 8 102 from increment 1611:1619 arg1 branching 1641:1649 branching 1641:1649 branching 1641:1649 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 8 102 from increment 1611:1619 arg1 fucosylation 1624:1635 fucosylation 1624:1635 fucosylation 1624:1635 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 7679920 1 103 theme culinaris 309:317 arg1 LCA 331:333 LCA 331:333 LCA 331:333 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 1 103 theme culinaris 309:317 arg1 agglutinin 319:328 Lens culinaris agglutinin 304:328 Lens culinaris agglutinin (LCA) 304:334 Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. 7679920 5 104 theme sugar 1159:1163 arg1 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 104 theme sugar 1159:1163 arg1 component 1182:1190 a major component 1174:1190 a major component 1174:1190 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 104 theme sugar 1159:1163 arg1 chain 1165:1169 a fucosylated triantennary sugar chain 1132:1169 a fucosylated triantennary sugar chain 1132:1169 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 2 105 theme liquid 496:501 arg1 chromatography 503:516 high performance liquid chromatography 479:516 high performance liquid chromatography 479:516 Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. 7679920 5 106 dep components 1207:1216 arg1 chain 1270:1274 a biantennary sugar chain 1250:1274 a biantennary sugar chain 1250:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 106 dep components 1207:1216 arg1 chain 1240:1244 a triantennary sugar chain 1219:1244 a triantennary sugar chain 1219:1244 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 5 106 dep components 1207:1216 arg1 components 1207:1216 two minor components 1197:1216 two minor components: a triantennary sugar chain and a biantennary sugar chain 1197:1274 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 4 107 theme sugar 915:919 arg1 chain 921:925 a biantennary sugar chain 901:925 a biantennary sugar chain 901:925 The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. 7679920 5 108 theme LCA-nonreactive 1098:1112 arg1 species 1114:1120 The Con A-nonreactive and LCA-nonreactive species 1072:1120 The Con A-nonreactive and LCA-nonreactive species 1072:1120 The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. 7679920 0 109 dep structures 13:22 arg1 presence 94:101 presence 94:101 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 0:158 Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. 7679920 8 110 theme neoplastic 1753:1762 arg1 diseases 1764:1771 neoplastic diseases 1753:1771 neoplastic diseases of the liver 1753:1784 These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver. 15316280 4 0 theme biantennary 651:661 arg1 structure 675:683 the abnormal biantennary sugar chain structure 638:683 the abnormal biantennary sugar chain structure 638:683 We hypothesized that the formation mechanism of the abnormal biantennary sugar chain structure is mainly caused by high GnT-IV activity. 15316280 3 1 theme much 452:455 arg1 research 457:464 much research 452:464 much research 452:464 In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. 15316280 1 2 theme cell 302:305 arg1 lines 307:311 cell lines 302:311 cell lines 302:311 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 5 3 theme cell 856:859 arg1 lines 861:865 three choriocarcinoma cell lines 834:865 three choriocarcinoma cell lines 834:865 To confirm this, we measured the N-acetylglucosaminyltransferase (GnT)-IV activity and hCG productivity in three choriocarcinoma cell lines, and selected JEG-3 cells. 15316280 4 4 theme abnormal 642:649 arg1 structure 675:683 the abnormal biantennary sugar chain structure 638:683 the abnormal biantennary sugar chain structure 638:683 We hypothesized that the formation mechanism of the abnormal biantennary sugar chain structure is mainly caused by high GnT-IV activity. 15316280 1 5 theme healthy 230:236 arg1 people 238:243 healthy people 230:243 healthy people 230:243 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 0 6 theme choriocarcinoma 96:110 arg1 JEG-3 123:127 JEG-3 123:127 JEG-3 123:127 Abnormal biantennary sugar chains are expressed in human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3. 15316280 0 6 theme choriocarcinoma 96:110 arg1 line 117:120 the choriocarcinoma cell line 92:120 the choriocarcinoma cell line 92:120 Abnormal biantennary sugar chains are expressed in human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3. 15316280 1 7 theme lines 307:311 arg1 types 293:297 some types 288:297 some types of cell lines 288:311 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 1 7 theme lines 307:311 arg1 structures 169:178 sugar chain structures 157:178 sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people 157:243 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 1 7 theme lines 307:311 arg1 types 252:256 three types 246:256 three types of trophoblastic disease 246:281 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 3 8 theme abnormal 479:486 arg1 structure 500:508 an abnormal biantennary structure 476:508 an abnormal biantennary structure 476:508 In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. 15316280 7 9 theme patients 1161:1168 arg1 samples 1134:1140 the urine samples 1124:1140 the urine samples of choriocarcinoma patients 1124:1168 We detected an abnormal biantennary structure, and the proportions were different from those previously reported in the urine samples of choriocarcinoma patients. 15316280 3 10 with hCG 467:469 arg1 structure 500:508 an abnormal biantennary structure 476:508 an abnormal biantennary structure 476:508 In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. 15316280 3 11 theme biantennary 488:498 arg1 structure 500:508 an abnormal biantennary structure 476:508 an abnormal biantennary structure 476:508 In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. 15316280 3 12 located detected 518:525 arg1 urine 534:538 the urine 530:538 the urine of choriocarcinoma or pregnant diabetic patients 530:587 In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. 15316280 3 12 located detected 518:525 arg2 hCG 467:469 hCG 467:469 hCG with an abnormal biantennary structure 467:508 In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. 15316280 5 13 theme -IV 797:799 arg1 activity 801:808 the N-acetylglucosaminyltransferase (GnT)-IV activity 756:808 the N-acetylglucosaminyltransferase (GnT)-IV activity 756:808 To confirm this, we measured the N-acetylglucosaminyltransferase (GnT)-IV activity and hCG productivity in three choriocarcinoma cell lines, and selected JEG-3 cells. 15316280 8 14 theme cells 1244:1248 arg1 usefulness 1224:1233 the usefulness 1220:1233 the usefulness of JEG-3 cells for further analyses of abnormal biantennary structure formation 1220:1313 These findings proved our hypothesis and suggest the usefulness of JEG-3 cells for further analyses of abnormal biantennary structure formation. 15316280 2 15 theme abnormal 337:344 arg1 structure 358:366 The abnormal biantennary structure 333:366 The abnormal biantennary structure of hCG 333:373 The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. 15316280 2 15 theme abnormal 337:344 arg1 marker 385:390 a good marker 378:390 a good marker for the diagnosis of malignant choriocarcinoma 378:437 The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. 15316280 8 16 theme structure 1295:1303 arg1 formation 1305:1313 abnormal biantennary structure formation 1274:1313 abnormal biantennary structure formation 1274:1313 These findings proved our hypothesis and suggest the usefulness of JEG-3 cells for further analyses of abnormal biantennary structure formation. 15316280 0 17 theme cell 112:115 arg1 JEG-3 123:127 JEG-3 123:127 JEG-3 123:127 Abnormal biantennary sugar chains are expressed in human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3. 15316280 0 17 theme cell 112:115 arg1 line 117:120 the choriocarcinoma cell line 92:120 the choriocarcinoma cell line 92:120 Abnormal biantennary sugar chains are expressed in human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3. 15316280 7 18 theme choriocarcinoma 1145:1159 arg1 patients 1161:1168 choriocarcinoma patients 1145:1168 choriocarcinoma patients 1145:1168 We detected an abnormal biantennary structure, and the proportions were different from those previously reported in the urine samples of choriocarcinoma patients. 15316280 7 19 theme urine 1128:1132 arg1 samples 1134:1140 the urine samples 1124:1140 the urine samples of choriocarcinoma patients 1124:1168 We detected an abnormal biantennary structure, and the proportions were different from those previously reported in the urine samples of choriocarcinoma patients. 15316280 1 20 theme sugar 157:161 arg1 structures 169:178 sugar chain structures 157:178 sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people 157:243 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 0 21 theme biantennary 9:19 arg1 chains 27:32 Abnormal biantennary sugar chains 0:32 Abnormal biantennary sugar chains 0:32 Abnormal biantennary sugar chains are expressed in human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3. 15316280 7 22 theme abnormal 1023:1030 arg1 structure 1044:1052 an abnormal biantennary structure 1020:1052 an abnormal biantennary structure 1020:1052 We detected an abnormal biantennary structure, and the proportions were different from those previously reported in the urine samples of choriocarcinoma patients. 15316280 1 23 theme chain 163:167 arg1 structures 169:178 sugar chain structures 157:178 sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people 157:243 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 0 24 theme Abnormal 0:7 arg1 chains 27:32 Abnormal biantennary sugar chains 0:32 Abnormal biantennary sugar chains 0:32 Abnormal biantennary sugar chains are expressed in human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3. 15316280 7 25 theme biantennary 1032:1042 arg1 structure 1044:1052 an abnormal biantennary structure 1020:1052 an abnormal biantennary structure 1020:1052 We detected an abnormal biantennary structure, and the proportions were different from those previously reported in the urine samples of choriocarcinoma patients. 15316280 5 26 theme hCG 814:816 arg1 productivity 818:829 hCG productivity 814:829 hCG productivity in three choriocarcinoma cell lines 814:865 To confirm this, we measured the N-acetylglucosaminyltransferase (GnT)-IV activity and hCG productivity in three choriocarcinoma cell lines, and selected JEG-3 cells. 15316280 4 27 theme formation 615:623 arg1 mechanism 625:633 the formation mechanism 611:633 the formation mechanism of the abnormal biantennary sugar chain structure 611:683 We hypothesized that the formation mechanism of the abnormal biantennary sugar chain structure is mainly caused by high GnT-IV activity. 15316280 5 28 theme N-acetylglucosaminyltransferase 760:790 arg1 activity 801:808 the N-acetylglucosaminyltransferase (GnT)-IV activity 756:808 the N-acetylglucosaminyltransferase (GnT)-IV activity 756:808 To confirm this, we measured the N-acetylglucosaminyltransferase (GnT)-IV activity and hCG productivity in three choriocarcinoma cell lines, and selected JEG-3 cells. 15316280 8 29 theme further 1254:1260 arg1 analyses 1262:1269 further analyses 1254:1269 further analyses of abnormal biantennary structure formation 1254:1313 These findings proved our hypothesis and suggest the usefulness of JEG-3 cells for further analyses of abnormal biantennary structure formation. 15316280 5 30 theme JEG-3 881:885 arg1 cells 887:891 JEG-3 cells 881:891 JEG-3 cells 881:891 To confirm this, we measured the N-acetylglucosaminyltransferase (GnT)-IV activity and hCG productivity in three choriocarcinoma cell lines, and selected JEG-3 cells. 15316280 4 31 theme high 705:708 arg1 activity 717:724 high GnT-IV activity 705:724 high GnT-IV activity 705:724 We hypothesized that the formation mechanism of the abnormal biantennary sugar chain structure is mainly caused by high GnT-IV activity. 15316280 2 32 theme good 380:383 arg1 structure 358:366 The abnormal biantennary structure 333:366 The abnormal biantennary structure of hCG 333:373 The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. 15316280 2 32 theme good 380:383 arg1 marker 385:390 a good marker 378:390 a good marker for the diagnosis of malignant choriocarcinoma 378:437 The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. 15316280 8 33 theme biantennary 1283:1293 arg1 formation 1305:1313 abnormal biantennary structure formation 1274:1313 abnormal biantennary structure formation 1274:1313 These findings proved our hypothesis and suggest the usefulness of JEG-3 cells for further analyses of abnormal biantennary structure formation. 15316280 1 34 theme human 183:187 arg1 hCG 213:215 hCG 213:215 hCG 213:215 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 1 34 theme human 183:187 arg1 gonadotropin 199:210 human chorionic gonadotropin 183:210 human chorionic gonadotropin (hCG) produced in healthy people 183:243 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 2 35 theme choriocarcinoma 423:437 arg1 diagnosis 400:408 the diagnosis 396:408 the diagnosis of malignant choriocarcinoma 396:437 The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. 15316280 1 36 theme trophoblastic 261:273 arg1 disease 275:281 trophoblastic disease 261:281 trophoblastic disease 261:281 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 1 37 theme chorionic 189:197 arg1 hCG 213:215 hCG 213:215 hCG 213:215 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 1 37 theme chorionic 189:197 arg1 gonadotropin 199:210 human chorionic gonadotropin 183:210 human chorionic gonadotropin (hCG) produced in healthy people 183:243 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 8 38 theme abnormal 1274:1281 arg1 formation 1305:1313 abnormal biantennary structure formation 1274:1313 abnormal biantennary structure formation 1274:1313 These findings proved our hypothesis and suggest the usefulness of JEG-3 cells for further analyses of abnormal biantennary structure formation. 15316280 2 39 theme hCG 371:373 arg1 structure 358:366 The abnormal biantennary structure 333:366 The abnormal biantennary structure of hCG 333:373 The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. 15316280 2 39 theme hCG 371:373 arg1 marker 385:390 a good marker 378:390 a good marker for the diagnosis of malignant choriocarcinoma 378:437 The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. 15316280 2 40 theme malignant 413:421 arg1 choriocarcinoma 423:437 malignant choriocarcinoma 413:437 malignant choriocarcinoma 413:437 The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. 15316280 1 41 theme disease 275:281 arg1 types 293:297 some types 288:297 some types of cell lines 288:311 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 1 41 theme disease 275:281 arg1 structures 169:178 sugar chain structures 157:178 sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people 157:243 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 1 41 theme disease 275:281 arg1 types 252:256 three types 246:256 three types of trophoblastic disease 246:281 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 6 42 theme JEG-3 947:951 arg1 cells 953:957 JEG-3 cells 947:957 JEG-3 cells 947:957 hCG samples were purified from medium conditioned by JEG-3 cells, and their sugar chain structures were analyzed. 15316280 3 43 theme patients 580:587 arg1 urine 534:538 the urine 530:538 the urine of choriocarcinoma or pregnant diabetic patients 530:587 In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. 15316280 1 44 theme gonadotropin 199:210 arg1 types 293:297 some types 288:297 some types of cell lines 288:311 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 1 44 theme gonadotropin 199:210 arg1 structures 169:178 sugar chain structures 157:178 sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people 157:243 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 1 44 theme gonadotropin 199:210 arg1 types 252:256 three types 246:256 three types of trophoblastic disease 246:281 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 15316280 0 45 theme human 51:55 arg1 gonadotropin 67:78 human chorionic gonadotropin 51:78 human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3 51:127 Abnormal biantennary sugar chains are expressed in human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3. 15316280 6 46 theme hCG 894:896 arg1 samples 898:904 hCG samples 894:904 hCG samples 894:904 hCG samples were purified from medium conditioned by JEG-3 cells, and their sugar chain structures were analyzed. 15316280 4 47 theme GnT-IV 710:715 arg1 activity 717:724 high GnT-IV activity 705:724 high GnT-IV activity 705:724 We hypothesized that the formation mechanism of the abnormal biantennary sugar chain structure is mainly caused by high GnT-IV activity. 15316280 5 48 from activity 801:808 arg1 lines 861:865 three choriocarcinoma cell lines 834:865 three choriocarcinoma cell lines 834:865 To confirm this, we measured the N-acetylglucosaminyltransferase (GnT)-IV activity and hCG productivity in three choriocarcinoma cell lines, and selected JEG-3 cells. 15316280 4 49 theme chain 669:673 arg1 structure 675:683 the abnormal biantennary sugar chain structure 638:683 the abnormal biantennary sugar chain structure 638:683 We hypothesized that the formation mechanism of the abnormal biantennary sugar chain structure is mainly caused by high GnT-IV activity. 15316280 7 50 from those 1095:1099 arg1 different 1080:1088 different 1080:1088 different 1080:1088 We detected an abnormal biantennary structure, and the proportions were different from those previously reported in the urine samples of choriocarcinoma patients. 15316280 7 50 from those 1095:1099 arg1 proportions 1063:1073 the proportions 1059:1073 the proportions 1059:1073 We detected an abnormal biantennary structure, and the proportions were different from those previously reported in the urine samples of choriocarcinoma patients. 15316280 4 51 theme sugar 663:667 arg1 structure 675:683 the abnormal biantennary sugar chain structure 638:683 the abnormal biantennary sugar chain structure 638:683 We hypothesized that the formation mechanism of the abnormal biantennary sugar chain structure is mainly caused by high GnT-IV activity. 15316280 8 52 theme JEG-3 1238:1242 arg1 cells 1244:1248 JEG-3 cells 1238:1248 JEG-3 cells 1238:1248 These findings proved our hypothesis and suggest the usefulness of JEG-3 cells for further analyses of abnormal biantennary structure formation. 15316280 3 53 theme pregnant 562:569 arg1 patients 580:587 pregnant diabetic patients 562:587 pregnant diabetic patients 562:587 In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. 15316280 6 54 theme sugar 970:974 arg1 structures 982:991 their sugar chain structures 964:991 their sugar chain structures 964:991 hCG samples were purified from medium conditioned by JEG-3 cells, and their sugar chain structures were analyzed. 15316280 3 55 theme diabetic 571:578 arg1 patients 580:587 pregnant diabetic patients 562:587 pregnant diabetic patients 562:587 In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. 15316280 5 56 from productivity 818:829 arg1 lines 861:865 three choriocarcinoma cell lines 834:865 three choriocarcinoma cell lines 834:865 To confirm this, we measured the N-acetylglucosaminyltransferase (GnT)-IV activity and hCG productivity in three choriocarcinoma cell lines, and selected JEG-3 cells. 15316280 4 57 theme structure 675:683 arg1 mechanism 625:633 the formation mechanism 611:633 the formation mechanism of the abnormal biantennary sugar chain structure 611:683 We hypothesized that the formation mechanism of the abnormal biantennary sugar chain structure is mainly caused by high GnT-IV activity. 15316280 8 58 theme formation 1305:1313 arg1 analyses 1262:1269 further analyses 1254:1269 further analyses of abnormal biantennary structure formation 1254:1313 These findings proved our hypothesis and suggest the usefulness of JEG-3 cells for further analyses of abnormal biantennary structure formation. 15316280 6 59 theme chain 976:980 arg1 structures 982:991 their sugar chain structures 964:991 their sugar chain structures 964:991 hCG samples were purified from medium conditioned by JEG-3 cells, and their sugar chain structures were analyzed. 15316280 3 60 theme choriocarcinoma 543:557 arg1 urine 534:538 the urine 530:538 the urine of choriocarcinoma or pregnant diabetic patients 530:587 In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. 15316280 5 61 theme choriocarcinoma 840:854 arg1 lines 861:865 three choriocarcinoma cell lines 834:865 three choriocarcinoma cell lines 834:865 To confirm this, we measured the N-acetylglucosaminyltransferase (GnT)-IV activity and hCG productivity in three choriocarcinoma cell lines, and selected JEG-3 cells. 15316280 2 62 theme biantennary 346:356 arg1 structure 358:366 The abnormal biantennary structure 333:366 The abnormal biantennary structure of hCG 333:373 The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. 15316280 2 62 theme biantennary 346:356 arg1 marker 385:390 a good marker 378:390 a good marker for the diagnosis of malignant choriocarcinoma 378:437 The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. 15316280 0 63 theme chorionic 57:65 arg1 gonadotropin 67:78 human chorionic gonadotropin 51:78 human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3 51:127 Abnormal biantennary sugar chains are expressed in human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3. 15316280 0 64 theme sugar 21:25 arg1 chains 27:32 Abnormal biantennary sugar chains 0:32 Abnormal biantennary sugar chains 0:32 Abnormal biantennary sugar chains are expressed in human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3. 15316280 1 65 theme past 139:142 arg1 decades 148:154 the past two decades 135:154 the past two decades 135:154 Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. 2297756 3 0 with bi- 652:654 arg1 chains 756:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 1 theme beta 721:724 arg1 beta 739:742 the Gal beta 1----4GlcNAc beta 1---- 713:748 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 6 2 theme outer 1188:1192 arg1 chain 1194:1198 a tetrasaccharide outer chain 1170:1198 a tetrasaccharide outer chain 1170:1198 However, it is of interest that the core portion of monoantennary oligosaccharide was not fucosylated and that of the tetraantennary oligosaccharide with a tetrasaccharide outer chain was completely fucosylated. 2297756 0 3 theme kasahara 81:88 arg1 phosphatase 68:78 an alkaline phosphatase 56:78 an alkaline phosphatase 56:78 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. 2297756 0 3 theme kasahara 81:88 arg1 isozyme 90:96 kasahara isozyme 81:96 kasahara isozyme 81:96 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. 2297756 4 4 from chain 893:897 arg1 arm 925:927 their Man alpha 1----6 arm 902:927 their Man alpha 1----6 arm 902:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 4 5 theme outer 887:891 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 0 6 link asparagine-linked 18:34 arg1 oligosaccharides 36:51 the asparagine-linked oligosaccharides 14:51 the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, 14:97 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. 2297756 2 7 theme acidic 347:352 arg1 components 354:363 acidic components 347:363 acidic components 347:363 Almost all of the oligosaccharides (98%) were acidic components, all of which can be converted to neutral oligosaccharides upon sialidase digestion. 2297756 5 8 theme sugar 1002:1006 arg1 chains 1008:1013 the sugar chains 998:1013 the sugar chains 998:1013 Both fucosylated and nonfucosylated trimannosyl cores were found in the sugar chains. 2297756 3 9 with combination 536:546 arg1 analysis 565:572 methylation analysis 553:572 methylation analysis 553:572 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 4 10 theme 1----3Gal 848:856 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 4 11 theme tetraantennary 776:789 arg1 chains 797:802 the tetraantennary sugar chains 772:802 the tetraantennary sugar chains 772:802 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 1 12 theme FL 284:285 arg1 cells 294:298 FL amnion cells 284:298 FL amnion cells 284:298 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 5 13 gly nonfucosylated 951:964 arg1 cores 978:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores were found in the sugar chains. 2297756 6 14 gly fucosylated 1106:1116 arg1 portion 1057:1063 the core portion 1048:1063 the core portion of monoantennary oligosaccharide 1048:1096 However, it is of interest that the core portion of monoantennary oligosaccharide was not fucosylated and that of the tetraantennary oligosaccharide with a tetrasaccharide outer chain was completely fucosylated. 2297756 3 15 contain contains 625:632 arg2 tetraantennary 667:680 tetraantennary 667:680 tetraantennary 667:680 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 15 contain contains 625:632 arg2 bi- 652:654 bi- 652:654 bi- 652:654 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 15 contain contains 625:632 arg1 phosphatase 601:611 the alkaline phosphatase 588:611 the alkaline phosphatase of FL cells 588:623 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 15 contain contains 625:632 arg2 mono- 645:649 mono- 645:649 mono- 645:649 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 15 contain contains 625:632 arg2 tri- 657:660 tri- 657:660 tri- 657:660 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 0 16 theme FL 113:114 arg1 cells 123:127 FL amnion cells 113:127 FL amnion cells 113:127 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. 2297756 3 17 theme outer 750:754 arg1 chains 756:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 4 18 theme 1----4GlcNAc 863:874 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 6 19 theme core 1052:1055 arg1 portion 1057:1063 the core portion 1048:1063 the core portion of monoantennary oligosaccharide 1048:1096 However, it is of interest that the core portion of monoantennary oligosaccharide was not fucosylated and that of the tetraantennary oligosaccharide with a tetrasaccharide outer chain was completely fucosylated. 2297756 3 20 theme methylation 553:563 arg1 analysis 565:572 methylation analysis 553:572 methylation analysis 553:572 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 4 21 theme beta 825:828 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 1 22 theme amnion 287:292 arg1 cells 294:298 FL amnion cells 284:298 FL amnion cells 284:298 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 1 23 attach released 185:192 arg1 phosphatase 229:239 an alkaline phosphatase 217:239 an alkaline phosphatase 217:239 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 1 23 attach released 185:192 arg1 isozyme 251:257 Kasahara isozyme 242:257 Kasahara isozyme 242:257 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 1 23 attach released 185:192 arg2 oligosaccharides 148:163 Asparagine-linked oligosaccharides 130:163 Asparagine-linked oligosaccharides 130:163 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 4 24 theme beta 858:861 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 4 25 theme sugar 791:795 arg1 chains 797:802 the tetraantennary sugar chains 772:802 the tetraantennary sugar chains 772:802 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 6 26 theme oligosaccharide 1082:1096 arg1 portion 1057:1063 the core portion 1048:1063 the core portion of monoantennary oligosaccharide 1048:1096 However, it is of interest that the core portion of monoantennary oligosaccharide was not fucosylated and that of the tetraantennary oligosaccharide with a tetrasaccharide outer chain was completely fucosylated. 2297756 3 27 theme beta 739:742 arg1 chains 756:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 4 28 theme 1---- 881:885 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 5 29 theme nonfucosylated 951:964 arg1 cores 978:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores were found in the sugar chains. 2297756 4 30 theme Man 908:910 arg1 arm 925:927 their Man alpha 1----6 arm 902:927 their Man alpha 1----6 arm 902:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 6 31 theme monoantennary 1068:1080 arg1 oligosaccharide 1082:1096 monoantennary oligosaccharide 1068:1096 monoantennary oligosaccharide 1068:1096 However, it is of interest that the core portion of monoantennary oligosaccharide was not fucosylated and that of the tetraantennary oligosaccharide with a tetrasaccharide outer chain was completely fucosylated. 2297756 6 32 with oligosaccharide 1149:1163 arg1 chain 1194:1198 a tetrasaccharide outer chain 1170:1198 a tetrasaccharide outer chain 1170:1198 However, it is of interest that the core portion of monoantennary oligosaccharide was not fucosylated and that of the tetraantennary oligosaccharide with a tetrasaccharide outer chain was completely fucosylated. 2297756 4 33 theme beta 876:879 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 5 34 theme trimannosyl 966:976 arg1 cores 978:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores were found in the sugar chains. 2297756 3 35 with tri- 657:660 arg1 chains 756:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 2 36 theme sialidase 429:437 arg1 digestion 439:447 sialidase digestion 429:447 sialidase digestion 429:447 Almost all of the oligosaccharides (98%) were acidic components, all of which can be converted to neutral oligosaccharides upon sialidase digestion. 2297756 5 37 located found 989:993 arg1 chains 1008:1013 the sugar chains 998:1013 the sugar chains 998:1013 Both fucosylated and nonfucosylated trimannosyl cores were found in the sugar chains. 2297756 5 37 located found 989:993 arg2 cores 978:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores were found in the sugar chains. 2297756 4 38 theme beta 843:846 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 3 39 from digestion 523:531 arg1 combination 536:546 combination 536:546 combination with methylation analysis 536:572 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 40 gly sialylated 634:643 arg1 mono- 645:649 mono- 645:649 mono- 645:649 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 6 41 theme tetrasaccharide 1172:1186 arg1 chain 1194:1198 a tetrasaccharide outer chain 1170:1198 a tetrasaccharide outer chain 1170:1198 However, it is of interest that the core portion of monoantennary oligosaccharide was not fucosylated and that of the tetraantennary oligosaccharide with a tetrasaccharide outer chain was completely fucosylated. 2297756 0 42 theme amnion 116:121 arg1 cells 123:127 FL amnion cells 113:127 FL amnion cells 113:127 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. 2297756 3 43 theme alkaline 592:599 arg1 phosphatase 601:611 the alkaline phosphatase 588:611 the alkaline phosphatase of FL cells 588:623 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 2 44 theme neutral 399:405 arg1 oligosaccharides 407:422 neutral oligosaccharides 399:422 neutral oligosaccharides 399:422 Almost all of the oligosaccharides (98%) were acidic components, all of which can be converted to neutral oligosaccharides upon sialidase digestion. 2297756 3 45 dep mono- 645:649 arg1 chains 701:706 complex type sugar chains 682:706 complex type sugar chains 682:706 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 6 46 theme tetraantennary 1134:1147 arg1 oligosaccharide 1149:1163 the tetraantennary oligosaccharide 1130:1163 the tetraantennary oligosaccharide with a tetrasaccharide outer chain 1130:1198 However, it is of interest that the core portion of monoantennary oligosaccharide was not fucosylated and that of the tetraantennary oligosaccharide with a tetrasaccharide outer chain was completely fucosylated. 2297756 4 47 theme 1----4GlcNAc 830:841 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 3 48 with tetraantennary 667:680 arg1 chains 756:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 49 theme Structural 450:459 arg1 analysis 461:468 Structural analysis 450:468 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis 450:572 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 0 50 theme oligosaccharides 36:51 arg1 Structures 0:9 Structures 0:9 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, 0:97 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. 2297756 5 51 gly fucosylated 935:945 arg1 cores 978:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores were found in the sugar chains. 2297756 0 52 theme asparagine-linked 18:34 arg1 oligosaccharides 36:51 the asparagine-linked oligosaccharides 14:51 the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, 14:97 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. 2297756 1 53 theme Kasahara 242:249 arg1 phosphatase 229:239 an alkaline phosphatase 217:239 an alkaline phosphatase 217:239 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 1 53 theme Kasahara 242:249 arg1 isozyme 251:257 Kasahara isozyme 242:257 Kasahara isozyme 242:257 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 0 54 theme alkaline 59:66 arg1 phosphatase 68:78 an alkaline phosphatase 56:78 an alkaline phosphatase 56:78 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. 2297756 0 54 theme alkaline 59:66 arg1 isozyme 90:96 kasahara isozyme 81:96 kasahara isozyme 81:96 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. 2297756 4 55 theme alpha 912:916 arg1 arm 925:927 their Man alpha 1----6 arm 902:927 their Man alpha 1----6 arm 902:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 3 56 theme FL 616:617 arg1 cells 619:623 FL cells 616:623 FL cells 616:623 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 57 theme 1----4GlcNAc 726:737 arg1 beta 739:742 the Gal beta 1----4GlcNAc beta 1---- 713:748 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 58 theme sequential 497:506 arg1 digestion 523:531 sequential exoglycosidase digestion 497:531 sequential exoglycosidase digestion in combination with methylation analysis 497:572 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 1 59 link Asparagine-linked 130:146 arg1 oligosaccharides 148:163 Asparagine-linked oligosaccharides 130:163 Asparagine-linked oligosaccharides 130:163 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 3 60 theme sugar 695:699 arg1 chains 701:706 complex type sugar chains 682:706 complex type sugar chains 682:706 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 61 theme cells 619:623 arg1 phosphatase 601:611 the alkaline phosphatase 588:611 the alkaline phosphatase of FL cells 588:623 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 62 theme exoglycosidase 508:521 arg1 digestion 523:531 sequential exoglycosidase digestion 497:531 sequential exoglycosidase digestion in combination with methylation analysis 497:572 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 63 theme sialylated 634:643 arg1 mono- 645:649 mono- 645:649 mono- 645:649 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 64 theme oligosaccharides 477:492 arg1 analysis 461:468 Structural analysis 450:468 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis 450:572 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 4 65 theme 1----6 918:923 arg1 arm 925:927 their Man alpha 1----6 arm 902:927 their Man alpha 1----6 arm 902:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 3 66 theme complex 682:688 arg1 chains 701:706 complex type sugar chains 682:706 complex type sugar chains 682:706 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 6 67 gly fucosylated 1215:1225 arg1 that 1122:1125 that 1122:1125 that 1122:1125 However, it is of interest that the core portion of monoantennary oligosaccharide was not fucosylated and that of the tetraantennary oligosaccharide with a tetrasaccharide outer chain was completely fucosylated. 2297756 1 68 theme Asparagine-linked 130:146 arg1 oligosaccharides 148:163 Asparagine-linked oligosaccharides 130:163 Asparagine-linked oligosaccharides 130:163 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 5 69 theme fucosylated 935:945 arg1 cores 978:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores 930:982 Both fucosylated and nonfucosylated trimannosyl cores were found in the sugar chains. 2297756 3 70 with mono- 645:649 arg1 chains 756:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 3 71 theme type 690:693 arg1 chains 701:706 complex type sugar chains 682:706 complex type sugar chains 682:706 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 4 72 theme Gal 821:823 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 1 73 theme alkaline 220:227 arg1 phosphatase 229:239 an alkaline phosphatase 217:239 an alkaline phosphatase 217:239 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 1 73 theme alkaline 220:227 arg1 isozyme 251:257 Kasahara isozyme 242:257 Kasahara isozyme 242:257 Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. 2297756 4 74 contain contain 804:810 arg1 Some 764:767 Some 764:767 Some 764:767 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 4 74 contain contain 804:810 arg2 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 4 74 contain contain 804:810 arg1 chains 797:802 the tetraantennary sugar chains 772:802 the tetraantennary sugar chains 772:802 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 2297756 0 75 theme phosphatase 68:78 arg1 oligosaccharides 36:51 the asparagine-linked oligosaccharides 14:51 the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, 14:97 Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells. 2297756 3 76 theme Gal 717:719 arg1 beta 739:742 the Gal beta 1----4GlcNAc beta 1---- 713:748 the Gal beta 1----4GlcNAc beta 1---- outer chains 713:761 Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. 2297756 4 77 theme single 814:819 arg1 chain 893:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain 812:897 a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm 812:927 Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. 30237853 6 0 theme hydrophilic 1115:1125 arg1 HILIC 1162:1166 HILIC 1162:1166 HILIC 1162:1166 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 6 0 theme hydrophilic 1115:1125 arg1 chromatography 1146:1159 hydrophilic interaction liquid chromatography 1115:1159 hydrophilic interaction liquid chromatography (HILIC) 1115:1167 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 4 1 theme deep 617:620 arg1 mapping 635:641 deep quantitative mapping 617:641 deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 617:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 10 2 theme PCa 1768:1770 arg1 detection 1772:1780 PCa detection 1768:1780 PCa detection 1768:1780 This study has generated a panel of intact glycopeptides that has a potential for PCa detection. 30237853 6 3 theme endo-/exoglycosidase 1212:1231 arg1 treatment 1233:1241 endo-/exoglycosidase treatment 1212:1241 endo-/exoglycosidase treatment 1212:1241 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 8 4 gly O-glycopeptides 1518:1532 arg2 O-glycopeptides 1518:1532 O-glycopeptides 1518:1532 O-glycopeptides 1518:1532 We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. 30237853 2 5 theme dynamic 377:383 arg1 glycosylation 407:419 their dynamic and cancer-associated glycosylation 371:419 their dynamic and cancer-associated glycosylation 371:419 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 9 6 dep = 1680:1680 arg1 ROC 1671:1673 ROC 1671:1673 ROC 1671:1673 Importantly, a panel of 56 intact N-glycopeptides perfectly discriminated PCa and BPH (ROC: AUC = 1). 30237853 2 7 theme great 268:272 arg1 potential 274:282 a great potential 266:282 a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation 266:419 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 6 8 theme SPE 1190:1192 arg1 HILIC 1162:1166 HILIC 1162:1166 HILIC 1162:1166 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 6 8 theme SPE 1190:1192 arg1 chromatography 1146:1159 hydrophilic interaction liquid chromatography 1115:1159 hydrophilic interaction liquid chromatography (HILIC) 1115:1167 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 6 9 dep SPE 1190:1192 arg1 enrichment 1200:1209 based enrichment 1194:1209 based enrichment 1194:1209 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 2 10 theme tumor 310:314 arg1 biomarkers 316:325 specific and sensitive tumor biomarkers 287:325 specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation 287:419 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 1 11 theme diagnostic 169:178 arg1 programs 190:197 prostate cancer (PCa) diagnostic screening programs 147:197 prostate cancer (PCa) diagnostic screening programs 147:197 Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. 30237853 10 12 contain has 1748:1750 arg1 panel 1713:1717 a panel 1711:1717 a panel of intact glycopeptides that has a potential for PCa detection 1711:1780 This study has generated a panel of intact glycopeptides that has a potential for PCa detection. 30237853 10 12 contain has 1748:1750 arg2 potential 1754:1762 a potential 1752:1762 a potential for PCa detection 1752:1780 This study has generated a panel of intact glycopeptides that has a potential for PCa detection. 30237853 6 13 theme titanium 1173:1180 arg1 dioxide 1182:1188 titanium dioxide 1173:1188 titanium dioxide 1173:1188 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 10 14 gly glycopeptides 1729:1741 arg2 glycopeptides 1729:1741 intact glycopeptides 1722:1741 intact glycopeptides 1722:1741 This study has generated a panel of intact glycopeptides that has a potential for PCa detection. 30237853 4 15 from urine 672:676 arg1 mapping 635:641 deep quantitative mapping 617:641 deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 617:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 5 16 theme Total 869:873 arg1 extracts 883:890 Total protein extracts 869:890 Total protein extracts 869:890 Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. 30237853 5 17 theme patients 955:962 arg1 urine 938:942 urine 938:942 urine of six PCa patients (Gleason score 7) and six BPH patients 938:1001 Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. 30237853 8 18 theme disease 1564:1570 arg1 conditions 1572:1581 the two disease conditions 1556:1581 the two disease conditions 1556:1581 We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. 30237853 2 19 theme untapped 243:250 arg1 resource 252:259 a hitherto largely untapped resource 224:259 a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation 224:419 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 6 20 theme peptide 1018:1024 arg1 mixtures 1026:1033 The resulting peptide mixtures 1004:1033 The resulting peptide mixtures 1004:1033 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 6 20 theme peptide 1018:1024 arg1 TMT-labeled 1040:1050 TMT-labeled 1040:1050 TMT-labeled 1040:1050 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 9 21 theme intact 1611:1616 arg1 N-glycopeptides 1618:1632 56 intact N-glycopeptides 1608:1632 56 intact N-glycopeptides 1608:1632 Importantly, a panel of 56 intact N-glycopeptides perfectly discriminated PCa and BPH (ROC: AUC = 1). 30237853 2 22 gly glycosylation 407:419 arg1 fluids 360:365 bodily fluids 353:365 bodily fluids 353:365 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 1 23 theme Novel 70:74 arg1 biomarkers 76:85 Novel biomarkers 70:85 Novel biomarkers 70:85 Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. 30237853 10 24 theme glycopeptides 1729:1741 arg1 panel 1713:1717 a panel 1711:1717 a panel of intact glycopeptides that has a potential for PCa detection 1711:1780 This study has generated a panel of intact glycopeptides that has a potential for PCa detection. 30237853 8 25 theme unique 1443:1448 arg1 sites 1466:1470 1,310 unique N-glycosylation sites 1437:1470 1,310 unique N-glycosylation sites 1437:1470 We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. 30237853 2 26 theme cancer-associated 389:405 arg1 glycosylation 407:419 their dynamic and cancer-associated glycosylation 371:419 their dynamic and cancer-associated glycosylation 371:419 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 4 27 from hyperplasia 789:799 arg1 PCa 763:765 PCa 763:765 PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 763:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 5 28 theme BPH 990:992 arg1 patients 994:1001 six BPH patients 986:1001 six BPH patients 986:1001 Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. 30237853 6 29 theme sample 1087:1092 arg1 processing 1094:1103 a multi-faceted sample processing 1071:1103 a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation 1071:1274 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 4 30 from O-glycoproteins 653:667 arg1 urine 672:676 urine 672:676 urine 672:676 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 4 31 theme benign 772:777 arg1 BPH 802:804 BPH 802:804 BPH 802:804 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 4 31 theme benign 772:777 arg1 hyperplasia 789:799 benign prostatic hyperplasia 772:799 benign prostatic hyperplasia (BPH) 772:805 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 4 31 theme benign 772:777 arg1 conditions 812:821 two conditions 808:821 two conditions that remain difficult to clinically stratify 808:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 3 32 theme quantitative 431:442 arg1 strategies 460:469 quantitative glycoproteomics strategies 431:469 quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen 431:542 However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. 30237853 0 33 theme Distinct 0:7 arg1 signatures 30:39 Distinct urinary glycoprotein signatures 0:39 Distinct urinary glycoprotein signatures in prostate cancer patients 0:67 Distinct urinary glycoprotein signatures in prostate cancer patients. 30237853 8 34 gly N-glycoproteins 1412:1426 arg1 N-glycoproteins 1412:1426 729 N-glycoproteins 1408:1426 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites 1408:1470 We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. 30237853 5 35 theme Gleason 965:971 arg1 score 973:977 Gleason score 7 965:979 Gleason score 7 965:979 Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. 30237853 5 35 theme Gleason 965:971 arg1 patients 955:962 six PCa patients 947:962 six PCa patients (Gleason score 7) 947:980 Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. 30237853 9 36 gly N-glycopeptides 1618:1632 arg2 N-glycopeptides 1618:1632 56 intact N-glycopeptides 1608:1632 56 intact N-glycopeptides 1608:1632 Importantly, a panel of 56 intact N-glycopeptides perfectly discriminated PCa and BPH (ROC: AUC = 1). 30237853 3 37 theme glycoprotein 491:502 arg1 markers 511:517 potential glycoprotein cancer markers 481:517 potential glycoprotein cancer markers 481:517 However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. 30237853 0 38 theme glycoprotein 17:28 arg1 signatures 30:39 Distinct urinary glycoprotein signatures 0:39 Distinct urinary glycoprotein signatures in prostate cancer patients 0:67 Distinct urinary glycoprotein signatures in prostate cancer patients. 30237853 1 39 theme prostate 112:119 arg1 PSA 139:141 PSA 139:141 PSA 139:141 Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. 30237853 1 39 theme prostate 112:119 arg1 antigen 130:136 prostate specific antigen 112:136 prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs 112:197 Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. 30237853 4 40 theme glycoproteomics 588:602 arg1 strategy 604:611 a glycoproteomics strategy 586:611 a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 586:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 10 41 theme intact 1722:1727 arg1 glycopeptides 1729:1741 intact glycopeptides 1722:1741 intact glycopeptides 1722:1741 This study has generated a panel of intact glycopeptides that has a potential for PCa detection. 30237853 8 42 gly N-glycosylation 1450:1464 arg2 sites 1466:1470 1,310 unique N-glycosylation sites 1437:1470 1,310 unique N-glycosylation sites 1437:1470 We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. 30237853 8 42 gly N-glycosylation 1450:1464 arg2 1,310 1437:1441 1,310 1437:1441 1,310 1437:1441 We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. 30237853 7 43 theme mass 1364:1367 arg1 spectrometry 1369:1380 high resolution mass spectrometry 1348:1380 high resolution mass spectrometry 1348:1380 The isolated N- and O-glycopeptides were detected and quantified using high resolution mass spectrometry. 30237853 8 44 theme unique 1497:1502 arg1 N- 1511:1512 954 and 965 unique intact N- 1485:1512 954 and 965 unique intact N- 1485:1512 We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. 30237853 3 45 theme complex 524:530 arg1 biospecimen 532:542 complex biospecimen 524:542 complex biospecimen 524:542 However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. 30237853 0 46 theme cancer 53:58 arg1 patients 60:67 prostate cancer patients 44:67 prostate cancer patients 44:67 Distinct urinary glycoprotein signatures in prostate cancer patients. 30237853 7 47 theme high 1348:1351 arg1 spectrometry 1369:1380 high resolution mass spectrometry 1348:1380 high resolution mass spectrometry 1348:1380 The isolated N- and O-glycopeptides were detected and quantified using high resolution mass spectrometry. 30237853 3 48 gly glycoprotein 491:502 arg1 glycoprotein 491:502 potential glycoprotein cancer markers 481:517 potential glycoprotein cancer markers 481:517 However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. 30237853 6 49 theme interaction 1127:1137 arg1 HILIC 1162:1166 HILIC 1162:1166 HILIC 1162:1166 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 6 49 theme interaction 1127:1137 arg1 chromatography 1146:1159 hydrophilic interaction liquid chromatography 1115:1159 hydrophilic interaction liquid chromatography (HILIC) 1115:1167 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 2 50 theme bodily 353:358 arg1 fluids 360:365 bodily fluids 353:365 bodily fluids 353:365 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 0 51 gly glycoprotein 17:28 arg1 glycoprotein 17:28 Distinct urinary glycoprotein signatures 0:39 Distinct urinary glycoprotein signatures in prostate cancer patients 0:67 Distinct urinary glycoprotein signatures in prostate cancer patients. 30237853 2 52 theme specific 287:294 arg1 biomarkers 316:325 specific and sensitive tumor biomarkers 287:325 specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation 287:419 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 2 53 from abundance 340:348 arg1 fluids 360:365 bodily fluids 353:365 bodily fluids 353:365 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 4 54 theme quantitative 622:633 arg1 mapping 635:641 deep quantitative mapping 617:641 deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 617:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 6 55 theme based 1194:1198 arg1 enrichment 1200:1209 based enrichment 1194:1209 based enrichment 1194:1209 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 2 56 theme sensitive 300:308 arg1 biomarkers 316:325 specific and sensitive tumor biomarkers 287:325 specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation 287:419 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 1 57 theme screening 180:188 arg1 programs 190:197 prostate cancer (PCa) diagnostic screening programs 147:197 prostate cancer (PCa) diagnostic screening programs 147:197 Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. 30237853 5 58 theme protein 875:881 arg1 extracts 883:890 Total protein extracts 869:890 Total protein extracts 869:890 Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. 30237853 2 59 with resource 252:259 arg1 potential 274:282 a great potential 266:282 a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation 266:419 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 1 60 theme specific 121:128 arg1 PSA 139:141 PSA 139:141 PSA 139:141 Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. 30237853 1 60 theme specific 121:128 arg1 antigen 130:136 prostate specific antigen 112:136 prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs 112:197 Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. 30237853 4 61 theme glycoproteome 733:745 arg1 value 720:724 the diagnostic value 705:724 the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 705:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 4 62 with mapping 635:641 arg1 view 685:688 a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 683:866 a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 683:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 5 63 theme PCa 951:953 arg1 score 973:977 Gleason score 7 965:979 Gleason score 7 965:979 Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. 30237853 5 63 theme PCa 951:953 arg1 patients 955:962 six PCa patients 947:962 six PCa patients (Gleason score 7) 947:980 Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. 30237853 6 64 theme HILIC-HPLC 1247:1256 arg1 pre-fractionation 1258:1274 HILIC-HPLC pre-fractionation 1247:1274 HILIC-HPLC pre-fractionation 1247:1274 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 7 65 theme isolated 1281:1288 arg1 N- 1290:1291 N- 1290:1291 N- 1290:1291 The isolated N- and O-glycopeptides were detected and quantified using high resolution mass spectrometry. 30237853 0 66 from signatures 30:39 arg1 patients 60:67 prostate cancer patients 44:67 prostate cancer patients 44:67 Distinct urinary glycoprotein signatures in prostate cancer patients. 30237853 4 67 theme diagnostic 709:718 arg1 value 720:724 the diagnostic value 705:724 the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 705:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 4 68 from N- 646:647 arg1 urine 672:676 urine 672:676 urine 672:676 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 1 69 theme prostate 147:154 arg1 cancer 156:161 prostate cancer 147:161 prostate cancer 147:161 Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. 30237853 6 70 theme resulting 1008:1016 arg1 mixtures 1026:1033 The resulting peptide mixtures 1004:1033 The resulting peptide mixtures 1004:1033 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 6 70 theme resulting 1008:1016 arg1 TMT-labeled 1040:1050 TMT-labeled 1040:1050 TMT-labeled 1040:1050 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 4 71 from mapping 635:641 arg1 urine 672:676 urine 672:676 urine 672:676 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 9 72 theme N-glycopeptides 1618:1632 arg1 panel 1599:1603 a panel 1597:1603 a panel of 56 intact N-glycopeptides 1597:1632 Importantly, a panel of 56 intact N-glycopeptides perfectly discriminated PCa and BPH (ROC: AUC = 1). 30237853 4 73 gly O-glycoproteins 653:667 arg1 O-glycoproteins 653:667 O-glycoproteins 653:667 O-glycoproteins 653:667 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 0 74 theme urinary 9:15 arg1 signatures 30:39 Distinct urinary glycoprotein signatures 0:39 Distinct urinary glycoprotein signatures in prostate cancer patients 0:67 Distinct urinary glycoprotein signatures in prostate cancer patients. 30237853 6 75 theme multi-faceted 1073:1085 arg1 processing 1094:1103 a multi-faceted sample processing 1071:1103 a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation 1071:1274 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 8 76 theme N-glycosylation 1450:1464 arg1 sites 1466:1470 1,310 unique N-glycosylation sites 1437:1470 1,310 unique N-glycosylation sites 1437:1470 We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. 30237853 3 77 theme glycoproteomics 444:458 arg1 strategies 460:469 quantitative glycoproteomics strategies 431:469 quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen 431:542 However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. 30237853 1 78 from antigen 130:136 arg1 programs 190:197 prostate cancer (PCa) diagnostic screening programs 147:197 prostate cancer (PCa) diagnostic screening programs 147:197 Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. 30237853 4 79 theme prostatic 779:787 arg1 BPH 802:804 BPH 802:804 BPH 802:804 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 4 79 theme prostatic 779:787 arg1 hyperplasia 789:799 benign prostatic hyperplasia 772:799 benign prostatic hyperplasia (BPH) 772:805 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 4 79 theme prostatic 779:787 arg1 conditions 812:821 two conditions 808:821 two conditions that remain difficult to clinically stratify 808:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 3 80 theme cancer 504:509 arg1 markers 511:517 potential glycoprotein cancer markers 481:517 potential glycoprotein cancer markers 481:517 However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. 30237853 0 81 theme prostate 44:51 arg1 patients 60:67 prostate cancer patients 44:67 prostate cancer patients 44:67 Distinct urinary glycoprotein signatures in prostate cancer patients. 30237853 7 82 gly O-glycopeptides 1297:1311 arg2 O-glycopeptides 1297:1311 O-glycopeptides 1297:1311 O-glycopeptides 1297:1311 The isolated N- and O-glycopeptides were detected and quantified using high resolution mass spectrometry. 30237853 7 83 theme resolution 1353:1362 arg1 spectrometry 1369:1380 high resolution mass spectrometry 1348:1380 high resolution mass spectrometry 1348:1380 The isolated N- and O-glycopeptides were detected and quantified using high resolution mass spectrometry. 30237853 1 84 dep diagnostic 169:178 arg1 cancer 156:161 prostate cancer 147:161 prostate cancer 147:161 Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. 30237853 3 85 theme potential 481:489 arg1 markers 511:517 potential glycoprotein cancer markers 481:517 potential glycoprotein cancer markers 481:517 However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. 30237853 3 86 dep strategies 460:469 arg1 detect 474:479 detect 474:479 to detect potential glycoprotein cancer markers from complex biospecimen 471:542 However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. 30237853 5 87 theme patients 994:1001 arg1 urine 938:942 urine 938:942 urine of six PCa patients (Gleason score 7) and six BPH patients 938:1001 Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. 30237853 4 88 theme N- 646:647 arg1 mapping 635:641 deep quantitative mapping 617:641 deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 617:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 30237853 8 89 theme intact 1504:1509 arg1 N- 1511:1512 954 and 965 unique intact N- 1485:1512 954 and 965 unique intact N- 1485:1512 We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. 30237853 2 90 theme due 327:329 arg1 biomarkers 316:325 specific and sensitive tumor biomarkers 287:325 specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation 287:419 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 2 91 from glycosylation 407:419 arg1 fluids 360:365 bodily fluids 353:365 bodily fluids 353:365 Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. 30237853 6 92 theme liquid 1139:1144 arg1 HILIC 1162:1166 HILIC 1162:1166 HILIC 1162:1166 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 6 92 theme liquid 1139:1144 arg1 chromatography 1146:1159 hydrophilic interaction liquid chromatography 1115:1159 hydrophilic interaction liquid chromatography (HILIC) 1115:1167 The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. 30237853 4 93 theme O-glycoproteins 653:667 arg1 mapping 635:641 deep quantitative mapping 617:641 deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify 617:866 Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. 8358150 2 0 theme enzymes 116:122 arg1 N-glycans 74:82 the N-glycans 70:82 the N-glycans of the kidney, liver and spleen enzymes 70:122 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 8358150 4 1 theme M 444:444 arg1 C 471:471 4 degrees C 461:471 4 degrees C 461:471 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 4 1 theme M 444:444 arg1 H2SO4 446:450 0.25 M H2SO4 439:450 0.25 M H2SO4 439:450 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 4 1 theme M 444:444 arg1 min 456:458 45 min 453:458 45 min 453:458 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 2 2 theme electrospray 148:159 arg1 spectrometry 166:177 electrospray mass spectrometry 148:177 electrospray mass spectrometry 148:177 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 8358150 6 3 theme hexasaccharide 857:870 arg1 trisaccharide 822:834 the trisaccharide 818:834 the trisaccharide 818:834 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 3 theme hexasaccharide 857:870 arg1 hexasaccharide 857:870 hexasaccharide 857:870 hexasaccharide 857:870 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 3 theme hexasaccharide 857:870 arg1 pentasaccharide 837:851 pentasaccharide 837:851 pentasaccharide 837:851 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 3 theme hexasaccharide 857:870 arg1 amounts 807:813 The relative amounts 794:813 The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide 794:870 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 2 4 theme spleen 109:114 arg1 enzymes 116:122 the kidney, liver and spleen enzymes 87:122 the kidney, liver and spleen enzymes 87:122 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 8358150 2 5 theme mass 161:164 arg1 spectrometry 166:177 electrospray mass spectrometry 148:177 electrospray mass spectrometry 148:177 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 8358150 2 6 theme Structural 39:48 arg1 characterization 50:65 Structural characterization 39:65 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 39:178 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 8358150 7 7 theme spleen 1105:1110 arg1 RNases 1126:1131 spleen non-secretory RNases 1105:1131 spleen non-secretory RNases 1105:1131 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 6 8 theme pentasaccharide 837:851 arg1 trisaccharide 822:834 the trisaccharide 818:834 the trisaccharide 818:834 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 8 theme pentasaccharide 837:851 arg1 hexasaccharide 857:870 hexasaccharide 857:870 hexasaccharide 857:870 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 8 theme pentasaccharide 837:851 arg1 pentasaccharide 837:851 pentasaccharide 837:851 pentasaccharide 837:851 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 8 theme pentasaccharide 837:851 arg1 amounts 807:813 The relative amounts 794:813 The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide 794:870 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 7 9 theme non-secretory 1036:1048 arg1 RNases 1050:1055 non-secretory RNases 1036:1055 non-secretory RNases 1036:1055 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 6 10 theme tissue 915:920 arg1 RNases 922:927 the different tissue RNases 901:927 the different tissue RNases 901:927 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 4 11 theme 0.25 439:442 arg1 M 444:444 M 444:444 M 444:444 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 3 12 theme peptide-N-glycosidase 215:235 arg1 F 237:237 peptide-N-glycosidase F 215:237 peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen 215:327 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 3 12 theme peptide-N-glycosidase 215:235 arg1 F 247:247 PNGase F 240:247 PNGase F 240:247 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 6 13 theme following 752:760 arg1 structures 762:771 the following structures 748:771 the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases 748:927 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 3 14 from RNases 284:289 arg1 F 237:237 peptide-N-glycosidase F 215:237 peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen 215:327 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 3 14 from RNases 284:289 arg1 F 247:247 PNGase F 240:247 PNGase F 240:247 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 5 15 theme electrospray 664:675 arg1 spectrometry 682:693 electrospray mass spectrometry 664:693 electrospray mass spectrometry 664:693 The N-glycans of the RNases were fractionated by Bio-Gel P-4 chromatography and analysed by 600 MHz 1H-NMR spectroscopy and electrospray mass spectrometry. 8358150 6 16 theme trisaccharide 822:834 arg1 trisaccharide 822:834 the trisaccharide 818:834 the trisaccharide 818:834 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 16 theme trisaccharide 822:834 arg1 hexasaccharide 857:870 hexasaccharide 857:870 hexasaccharide 857:870 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 16 theme trisaccharide 822:834 arg1 pentasaccharide 837:851 pentasaccharide 837:851 pentasaccharide 837:851 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 16 theme trisaccharide 822:834 arg1 amounts 807:813 The relative amounts 794:813 The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide 794:870 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 7 17 dep one 1172:1174 arg1 another 1176:1182 another 1176:1182 another 1176:1182 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 5 18 theme mass 677:680 arg1 spectrometry 682:693 electrospray mass spectrometry 664:693 electrospray mass spectrometry 664:693 The N-glycans of the RNases were fractionated by Bio-Gel P-4 chromatography and analysed by 600 MHz 1H-NMR spectroscopy and electrospray mass spectrometry. 8358150 7 19 from kidney 1087:1092 arg1 identical 1158:1166 identical 1158:1166 identical 1158:1166 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 19 from kidney 1087:1092 arg1 if 1151:1152 if 1151:1152 if 1151:1152 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 19 from kidney 1087:1092 arg1 N-glycans 1072:1080 the N-glycans 1068:1080 the N-glycans from kidney, liver and spleen non-secretory RNases 1068:1131 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 19 from kidney 1087:1092 arg1 similar 1142:1148 similar 1142:1148 similar 1142:1148 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 4 20 dep include 400:406 arg1 C 471:471 4 degrees C 461:471 4 degrees C 461:471 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 4 20 dep include 400:406 arg1 H2SO4 446:450 0.25 M H2SO4 439:450 0.25 M H2SO4 439:450 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 4 20 dep include 400:406 arg1 min 456:458 45 min 453:458 45 min 453:458 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 0 21 theme non-secretory 6:18 arg1 ribonucleases 20:32 Human non-secretory ribonucleases 0:32 Human non-secretory ribonucleases. 0:33 Human non-secretory ribonucleases. 8358150 2 22 theme NMR 127:129 arg1 spectroscopy 131:142 NMR spectroscopy 127:142 NMR spectroscopy 127:142 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 8358150 3 23 theme PNGase 240:245 arg1 F 237:237 peptide-N-glycosidase F 215:237 peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen 215:327 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 3 23 theme PNGase 240:245 arg1 F 247:247 PNGase F 240:247 PNGase F 240:247 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 6 24 dep see 784:786 arg1 [formula 774:781 [formula 774:781 [formula 774:781 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 5 25 theme MHz 636:638 arg1 spectroscopy 647:658 600 MHz 1H-NMR spectroscopy 632:658 600 MHz 1H-NMR spectroscopy 632:658 The N-glycans of the RNases were fractionated by Bio-Gel P-4 chromatography and analysed by 600 MHz 1H-NMR spectroscopy and electrospray mass spectrometry. 8358150 0 26 theme Human 0:4 arg1 ribonucleases 20:32 Human non-secretory ribonucleases 0:32 Human non-secretory ribonucleases. 0:33 Human non-secretory ribonucleases. 8358150 5 27 theme RNases 561:566 arg1 N-glycans 544:552 The N-glycans 540:552 The N-glycans of the RNases 540:566 The N-glycans of the RNases were fractionated by Bio-Gel P-4 chromatography and analysed by 600 MHz 1H-NMR spectroscopy and electrospray mass spectrometry. 8358150 4 28 theme procedures 367:376 arg1 one 379:381 one 379:381 one 379:381 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 4 28 theme procedures 367:376 arg1 procedures 367:376 two procedures 363:376 two procedures 363:376 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 7 29 dep similar 1142:1148 arg1 identical 1158:1166 identical 1158:1166 identical 1158:1166 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 29 dep similar 1142:1148 arg1 if 1151:1152 if 1151:1152 if 1151:1152 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 29 dep similar 1142:1148 arg1 N-glycans 1072:1080 the N-glycans 1068:1080 the N-glycans from kidney, liver and spleen non-secretory RNases 1068:1131 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 29 dep similar 1142:1148 arg1 similar 1142:1148 similar 1142:1148 similar 1142:1148 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 6 30 theme relative 798:805 arg1 trisaccharide 822:834 the trisaccharide 818:834 the trisaccharide 818:834 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 30 theme relative 798:805 arg1 hexasaccharide 857:870 hexasaccharide 857:870 hexasaccharide 857:870 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 30 theme relative 798:805 arg1 pentasaccharide 837:851 pentasaccharide 837:851 pentasaccharide 837:851 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 30 theme relative 798:805 arg1 amounts 807:813 The relative amounts 794:813 The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide 794:870 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 2 31 theme N-glycans 74:82 arg1 characterization 50:65 Structural characterization 39:65 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 39:178 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 8358150 3 32 theme non-secretory 270:282 arg1 RNases 284:289 purified human non-secretory RNases 255:289 purified human non-secretory RNases derived from kidney, liver and spleen 255:327 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 6 33 theme non-secretory 705:717 arg1 preparations 725:736 All four non-secretory RNase preparations 696:736 All four non-secretory RNase preparations 696:736 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 34 theme RNase 719:723 arg1 preparations 725:736 All four non-secretory RNase preparations 696:736 All four non-secretory RNase preparations 696:736 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 35 theme different 905:913 arg1 RNases 922:927 the different tissue RNases 901:927 the different tissue RNases 901:927 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 5 36 theme 600 632:634 arg1 MHz 636:638 MHz 636:638 MHz 636:638 The N-glycans of the RNases were fractionated by Bio-Gel P-4 chromatography and analysed by 600 MHz 1H-NMR spectroscopy and electrospray mass spectrometry. 8358150 4 37 theme acid 418:421 arg1 treatment 423:431 the usual acid treatment 408:431 the usual acid treatment step 408:436 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 4 38 theme acid 491:494 arg1 treatment 496:504 acid treatment 491:504 acid treatment 491:504 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 7 39 dep alter 1013:1017 arg1 identical 1158:1166 identical 1158:1166 identical 1158:1166 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 39 dep alter 1013:1017 arg1 if 1151:1152 if 1151:1152 if 1151:1152 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 39 dep alter 1013:1017 arg1 N-glycans 1072:1080 the N-glycans 1068:1080 the N-glycans from kidney, liver and spleen non-secretory RNases 1068:1131 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 39 dep alter 1013:1017 arg1 i 961:961 i 961:961 i 961:961 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 39 dep alter 1013:1017 arg1 different 1189:1197 different 1189:1197 different 1189:1197 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 39 dep alter 1013:1017 arg1 ii 1059:1060 ii 1059:1060 ii 1059:1060 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 39 dep alter 1013:1017 arg1 similar 1142:1148 similar 1142:1148 similar 1142:1148 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 39 dep alter 1013:1017 arg1 that 1063:1066 that 1063:1066 that 1063:1066 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 3 40 attach derived 291:297 arg1 spleen 322:327 spleen 322:327 spleen 322:327 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 3 40 attach derived 291:297 arg1 kidney 304:309 kidney 304:309 kidney 304:309 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 3 40 attach derived 291:297 arg1 liver 312:316 liver 312:316 liver 312:316 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 3 40 attach derived 291:297 arg2 RNases 284:289 purified human non-secretory RNases 255:289 purified human non-secretory RNases derived from kidney, liver and spleen 255:327 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 3 41 theme purified 255:262 arg1 RNases 284:289 purified human non-secretory RNases 255:289 purified human non-secretory RNases derived from kidney, liver and spleen 255:327 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 4 42 theme usual 412:416 arg1 treatment 423:431 the usual acid treatment 408:431 the usual acid treatment step 408:436 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 6 43 dep structures 762:771 arg1 see 784:786 see 784:786 see text 784:791 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 43 dep structures 762:771 arg1 appeared 872:879 appeared 872:879 appeared to vary slightly in the different tissue RNases 872:927 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 2 44 theme liver 99:103 arg1 enzymes 116:122 the kidney, liver and spleen enzymes 87:122 the kidney, liver and spleen enzymes 87:122 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 8358150 3 45 theme human 264:268 arg1 RNases 284:289 purified human non-secretory RNases 255:289 purified human non-secretory RNases derived from kidney, liver and spleen 255:327 The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. 8358150 4 46 theme spleen 334:339 arg1 RNase 341:345 The spleen RNase 330:345 The spleen RNase 330:345 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 6 47 contain contained 738:746 arg1 preparations 725:736 All four non-secretory RNase preparations 696:736 All four non-secretory RNase preparations 696:736 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 6 47 contain contained 738:746 arg2 structures 762:771 the following structures 748:771 the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases 748:927 All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. 8358150 4 48 theme degrees 463:469 arg1 C 471:471 4 degrees C 461:471 4 degrees C 461:471 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 4 48 theme degrees 463:469 arg1 H2SO4 446:450 0.25 M H2SO4 439:450 0.25 M H2SO4 439:450 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 5 49 theme P-4 597:599 arg1 chromatography 601:614 Bio-Gel P-4 chromatography 589:614 Bio-Gel P-4 chromatography 589:614 The N-glycans of the RNases were fractionated by Bio-Gel P-4 chromatography and analysed by 600 MHz 1H-NMR spectroscopy and electrospray mass spectrometry. 8358150 4 50 theme treatment 423:431 arg1 step 433:436 the usual acid treatment step 408:436 the usual acid treatment step 408:436 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 5 51 theme 1H-NMR 640:645 arg1 spectroscopy 647:658 600 MHz 1H-NMR spectroscopy 632:658 600 MHz 1H-NMR spectroscopy 632:658 The N-glycans of the RNases were fractionated by Bio-Gel P-4 chromatography and analysed by 600 MHz 1H-NMR spectroscopy and electrospray mass spectrometry. 8358150 2 52 theme kidney 91:96 arg1 enzymes 116:122 the kidney, liver and spleen enzymes 87:122 the kidney, liver and spleen enzymes 87:122 Structural characterization of the N-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. 8358150 7 53 theme N-glycan 1208:1215 arg1 structures 1217:1226 the N-glycan structures 1204:1226 the N-glycan structures reported for secretory RNase 1204:1255 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 54 from RNases 1126:1131 arg1 identical 1158:1166 identical 1158:1166 identical 1158:1166 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 54 from RNases 1126:1131 arg1 if 1151:1152 if 1151:1152 if 1151:1152 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 54 from RNases 1126:1131 arg1 N-glycans 1072:1080 the N-glycans 1068:1080 the N-glycans from kidney, liver and spleen non-secretory RNases 1068:1131 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 54 from RNases 1126:1131 arg1 similar 1142:1148 similar 1142:1148 similar 1142:1148 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 55 theme non-secretory 1112:1124 arg1 RNases 1126:1131 spleen non-secretory RNases 1105:1131 spleen non-secretory RNases 1105:1131 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 56 from structures 1217:1226 arg1 different 1189:1197 different 1189:1197 different 1189:1197 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 57 theme overall 934:940 arg1 results 942:948 The overall results 930:948 The overall results 930:948 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 4 58 theme carbohydrate 517:528 arg1 moieties 530:537 the carbohydrate moieties 513:537 the carbohydrate moieties 513:537 The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. 8358150 7 59 theme acid 969:972 arg1 treatment 974:982 acid treatment 969:982 acid treatment during purification 969:1002 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 5 60 theme Bio-Gel 589:595 arg1 chromatography 601:614 Bio-Gel P-4 chromatography 589:614 Bio-Gel P-4 chromatography 589:614 The N-glycans of the RNases were fractionated by Bio-Gel P-4 chromatography and analysed by 600 MHz 1H-NMR spectroscopy and electrospray mass spectrometry. 8358150 7 61 theme secretory 1241:1249 arg1 RNase 1251:1255 secretory RNase 1241:1255 secretory RNase 1241:1255 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 62 from liver 1095:1099 arg1 identical 1158:1166 identical 1158:1166 identical 1158:1166 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 62 from liver 1095:1099 arg1 if 1151:1152 if 1151:1152 if 1151:1152 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 62 from liver 1095:1099 arg1 N-glycans 1072:1080 the N-glycans 1068:1080 the N-glycans from kidney, liver and spleen non-secretory RNases 1068:1131 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 62 from liver 1095:1099 arg1 similar 1142:1148 similar 1142:1148 similar 1142:1148 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 8358150 7 63 theme RNases 1050:1055 arg1 N-glycans 1023:1031 the N-glycans 1019:1031 the N-glycans of non-secretory RNases 1019:1055 The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. 11588155 0 0 theme normal 96:101 arg1 plasma 122:127 normal and hyperlipidemic plasma 96:127 normal and hyperlipidemic plasma 96:127 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 5 1 theme hypercholesterolemic 1182:1201 arg1 subjects 1203:1210 normolipidemic or hypercholesterolemic subjects 1164:1210 normolipidemic or hypercholesterolemic subjects 1164:1210 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 7 2 from deficiency 1415:1424 arg1 LDL 1441:1443 small dense LDL 1429:1443 small dense LDL 1429:1443 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and in the most buoyant subpopulation. 11588155 7 2 from deficiency 1415:1424 arg1 subpopulation 1469:1481 the most buoyant subpopulation 1452:1481 the most buoyant subpopulation 1452:1481 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and in the most buoyant subpopulation. 11588155 5 3 theme d 1034:1034 arg1 1.018-1.023 1038:1048 d = 1.018-1.023 1034:1048 d = 1.018-1.023 1034:1048 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 1 4 theme low-density 373:383 arg1 LDL 398:400 LDL 398:400 LDL 398:400 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 1 4 theme low-density 373:383 arg1 lipoprotein 385:395 low-density lipoprotein 373:395 low-density lipoprotein (LDL) 373:401 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 0 5 theme LDL 211:213 arg1 particles 215:223 small dense LDL particles 199:223 small dense LDL particles 199:223 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 3 6 theme matrix-assisted 580:594 arg1 spectrometry 629:640 matrix-assisted laser desorption/ionization mass spectrometry 580:640 matrix-assisted laser desorption/ionization mass spectrometry 580:640 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 8 7 theme dense 1575:1579 arg1 LDL 1581:1583 small dense LDL 1569:1583 small dense LDL 1569:1583 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 0 8 theme hyperlipidemic 107:120 arg1 plasma 122:127 normal and hyperlipidemic plasma 96:127 normal and hyperlipidemic plasma 96:127 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 1 9 theme lipoprotein 385:395 arg1 properties 359:368 the atherogenic properties 343:368 the atherogenic properties of low-density lipoprotein (LDL) 343:401 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 8 10 theme acid 1561:1564 arg1 deficiency 1540:1549 the apparent deficiency 1527:1549 the apparent deficiency of sialic acid in small dense LDL 1527:1583 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 4 11 theme glycans 894:900 arg1 diversity 869:877 diversity 869:877 diversity 869:877 The distribution and diversity of the apoB100 glycans isolated from all individuals was highly conserved. 11588155 4 11 theme glycans 894:900 arg1 distribution 852:863 distribution 852:863 distribution 852:863 The distribution and diversity of the apoB100 glycans isolated from all individuals was highly conserved. 11588155 5 12 theme apoB100 982:988 arg1 composition 967:977 The N-glycan composition 954:977 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) 954:1146 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 3 13 theme mass 624:627 arg1 spectrometry 629:640 matrix-assisted laser desorption/ionization mass spectrometry 580:640 matrix-assisted laser desorption/ionization mass spectrometry 580:640 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 2 14 theme apoB100 420:426 arg1 glycans 428:434 LDL apoB100 glycans 416:434 LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 416:528 We analyzed LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects. 11588155 8 15 theme sialic 1554:1559 arg1 acid 1561:1564 sialic acid 1554:1564 sialic acid 1554:1564 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 5 16 theme = 1036:1036 arg1 1.018-1.023 1038:1048 d = 1.018-1.023 1034:1048 d = 1.018-1.023 1034:1048 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 8 17 from deficiency 1540:1549 arg1 LDL 1581:1583 small dense LDL 1569:1583 small dense LDL 1569:1583 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 5 18 theme = 1082:1082 arg1 d 1080:1080 d = 1.030-1.040 1080:1094 d = 1.030-1.040 1080:1094 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 8 19 theme apoB100 1614:1620 arg1 invariable 1646:1655 invariable 1646:1655 invariable 1646:1655 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 8 19 theme apoB100 1614:1620 arg1 composition 1631:1641 the global apoB100 N-glycan composition 1603:1641 the global apoB100 N-glycan composition 1603:1641 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 2 20 theme LDL 416:418 arg1 glycans 428:434 LDL apoB100 glycans 416:434 LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 416:528 We analyzed LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects. 11588155 5 21 theme normolipidemic 1164:1177 arg1 subjects 1203:1210 normolipidemic or hypercholesterolemic subjects 1164:1210 normolipidemic or hypercholesterolemic subjects 1164:1210 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 8 22 from invariable 1646:1655 arg1 groups 1672:1677 the patient groups 1660:1677 the patient groups studied 1660:1685 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 4 23 attach isolated 902:909 arg1 individuals 920:930 all individuals 916:930 all individuals 916:930 The distribution and diversity of the apoB100 glycans isolated from all individuals was highly conserved. 11588155 4 23 attach isolated 902:909 arg2 glycans 894:900 the apoB100 glycans 882:900 the apoB100 glycans isolated from all individuals 882:930 The distribution and diversity of the apoB100 glycans isolated from all individuals was highly conserved. 11588155 6 24 theme " 1264:1264 arg1 glycans 1274:1280 "desialylated" apoB100 glycans 1251:1280 "desialylated" apoB100 glycans 1251:1280 Furthermore, we found no evidence for "desialylated" apoB100 glycans in any of the samples analyzed. 11588155 5 25 theme = 1128:1128 arg1 g/ml 1142:1145 d = 1.051-1.065 g/ml 1126:1145 d = 1.051-1.065 g/ml 1126:1145 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 26 attach derived 990:996 arg2 LDL1 1028:1031 LDL1 1028:1031 LDL1 1028:1031 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 26 attach derived 990:996 arg1 subpopulations 1012:1025 five LDL subpopulations 1003:1025 five LDL subpopulations 1003:1025 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 26 attach derived 990:996 arg2 apoB100 982:988 apoB100 982:988 apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) 982:1146 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 27 theme = 1059:1059 arg1 d 1057:1057 d = 1.023-1.030 1057:1071 d = 1.023-1.030 1057:1071 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 0 28 theme apolipoprotein 26:39 arg1 B100 41:44 human apolipoprotein B100 20:44 human apolipoprotein B100 20:44 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 1 29 theme sialylation 312:322 arg1 B100 279:282 apolipoprotein (apo) B100 258:282 apolipoprotein (apo) B100 258:282 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 1 29 theme sialylation 312:322 arg1 degree 302:307 particularly its degree 285:307 particularly its degree of sialylation 285:322 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 7 30 theme small 1429:1433 arg1 LDL 1441:1443 small dense LDL 1429:1443 small dense LDL 1429:1443 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and in the most buoyant subpopulation. 11588155 5 31 dep LDL1 1028:1031 arg1 LDL4 1097:1100 LDL4 1097:1100 LDL4 1097:1100 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 31 dep LDL1 1028:1031 arg1 LDL5 1120:1123 LDL5 1120:1123 LDL5 1120:1123 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 31 dep LDL1 1028:1031 arg1 LDL2 1051:1054 LDL2 1051:1054 LDL2 1051:1054 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 31 dep LDL1 1028:1031 arg1 LDL3 1074:1077 LDL3 1074:1077 LDL3 1074:1077 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 31 dep LDL1 1028:1031 arg1 d 1080:1080 d = 1.030-1.040 1080:1094 d = 1.030-1.040 1080:1094 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 31 dep LDL1 1028:1031 arg1 d 1103:1103 d = 1.040-1.051 1103:1117 d = 1.040-1.051 1103:1117 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 31 dep LDL1 1028:1031 arg1 d 1057:1057 d = 1.023-1.030 1057:1071 d = 1.023-1.030 1057:1071 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 31 dep LDL1 1028:1031 arg1 g/ml 1142:1145 d = 1.051-1.065 g/ml 1126:1145 d = 1.051-1.065 g/ml 1126:1145 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 31 dep LDL1 1028:1031 arg1 1.018-1.023 1038:1048 d = 1.018-1.023 1034:1048 d = 1.018-1.023 1034:1048 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 1 32 theme carbohydrate 230:241 arg1 composition 243:253 The carbohydrate composition 226:253 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, 226:323 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 0 33 theme human 20:24 arg1 B100 41:44 human apolipoprotein B100 20:44 human apolipoprotein B100 20:44 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 8 34 theme novel 1505:1509 arg1 explanation 1511:1521 a novel explanation 1503:1521 a novel explanation for the apparent deficiency of sialic acid in small dense LDL 1503:1583 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 5 35 theme 1.051-1.065 1130:1140 arg1 g/ml 1142:1145 d = 1.051-1.065 g/ml 1126:1145 d = 1.051-1.065 g/ml 1126:1145 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 3 36 theme labeled 667:673 arg1 oligosaccharides 675:690 fluorescently labeled oligosaccharides 653:690 fluorescently labeled oligosaccharides 653:690 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 5 37 theme N-glycan 958:965 arg1 composition 967:977 The N-glycan composition 954:977 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) 954:1146 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 7 38 theme ganglioside 1348:1358 arg1 Analysis 1314:1321 Analysis 1314:1321 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, 1314:1402 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and in the most buoyant subpopulation. 11588155 8 39 theme N-glycan 1622:1629 arg1 invariable 1646:1655 invariable 1646:1655 invariable 1646:1655 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 8 39 theme N-glycan 1622:1629 arg1 composition 1631:1641 the global apoB100 N-glycan composition 1603:1641 the global apoB100 N-glycan composition 1603:1641 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 8 40 from groups 1672:1677 arg1 invariable 1646:1655 invariable 1646:1655 invariable 1646:1655 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 8 40 from groups 1672:1677 arg1 composition 1631:1641 the global apoB100 N-glycan composition 1603:1641 the global apoB100 N-glycan composition 1603:1641 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 8 41 theme global 1607:1612 arg1 invariable 1646:1655 invariable 1646:1655 invariable 1646:1655 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 8 41 theme global 1607:1612 arg1 composition 1631:1641 the global apoB100 N-glycan composition 1603:1641 the global apoB100 N-glycan composition 1603:1641 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 6 42 theme desialylated 1252:1263 arg1 glycans 1274:1280 "desialylated" apoB100 glycans 1251:1280 "desialylated" apoB100 glycans 1251:1280 Furthermore, we found no evidence for "desialylated" apoB100 glycans in any of the samples analyzed. 11588155 7 43 theme LDL 1344:1346 arg1 alpha-N-acetylneuraminyllactosyl-ceramide 1361:1401 alpha-N-acetylneuraminyllactosyl-ceramide 1361:1401 alpha-N-acetylneuraminyllactosyl-ceramide 1361:1401 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and in the most buoyant subpopulation. 11588155 7 43 theme LDL 1344:1346 arg1 ganglioside 1348:1358 the most abundant LDL ganglioside 1326:1358 the most abundant LDL ganglioside 1326:1358 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and in the most buoyant subpopulation. 11588155 0 44 theme B100 41:44 arg1 Characterization 0:15 Characterization 0:15 Characterization of human apolipoprotein B100 0:44 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 6 45 gly desialylated 1252:1263 arg1 glycans 1274:1280 "desialylated" apoB100 glycans 1251:1280 "desialylated" apoB100 glycans 1251:1280 Furthermore, we found no evidence for "desialylated" apoB100 glycans in any of the samples analyzed. 11588155 0 46 theme alpha-N-acetylneuraminyllactosyl-ceramide 144:184 arg1 deficiency 130:139 deficiency 130:139 deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles 130:223 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 8 47 theme apparent 1531:1538 arg1 deficiency 1540:1549 the apparent deficiency 1527:1549 the apparent deficiency of sialic acid in small dense LDL 1527:1583 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 2 48 theme hypercholesterolemic 465:484 arg1 subjects 521:528 normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 449:528 normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 449:528 We analyzed LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects. 11588155 1 49 theme apolipoprotein 258:271 arg1 B100 279:282 apolipoprotein (apo) B100 258:282 apolipoprotein (apo) B100 258:282 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 1 49 theme apolipoprotein 258:271 arg1 degree 302:307 particularly its degree 285:307 particularly its degree of sialylation 285:322 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 0 50 theme LDL 66:68 arg1 subfractions 70:81 LDL subfractions 66:81 LDL subfractions derived from normal and hyperlipidemic plasma 66:127 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 8 51 theme patient 1664:1670 arg1 groups 1672:1677 the patient groups 1660:1677 the patient groups studied 1660:1685 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 7 52 theme dense 1435:1439 arg1 LDL 1441:1443 small dense LDL 1429:1443 small dense LDL 1429:1443 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and in the most buoyant subpopulation. 11588155 2 53 attach derived 436:442 arg1 subjects 521:528 normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 449:528 normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 449:528 We analyzed LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects. 11588155 2 53 attach derived 436:442 arg2 glycans 428:434 LDL apoB100 glycans 416:434 LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 416:528 We analyzed LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects. 11588155 0 54 dep oligosaccharides 46:61 arg1 deficiency 130:139 deficiency 130:139 deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles 130:223 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 0 55 attach derived 83:89 arg2 subfractions 70:81 LDL subfractions 66:81 LDL subfractions derived from normal and hyperlipidemic plasma 66:127 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 0 55 attach derived 83:89 arg1 plasma 122:127 normal and hyperlipidemic plasma 96:127 normal and hyperlipidemic plasma 96:127 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 3 56 theme carbohydrate 552:563 arg1 sequencing 565:574 exoglycosidase carbohydrate sequencing 537:574 exoglycosidase carbohydrate sequencing 537:574 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 2 57 theme hypertriglyceridemic 491:510 arg1 subjects 521:528 normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 449:528 normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 449:528 We analyzed LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects. 11588155 8 58 theme small 1569:1573 arg1 LDL 1581:1583 small dense LDL 1569:1583 small dense LDL 1569:1583 These data provide a novel explanation for the apparent deficiency of sialic acid in small dense LDL and indicate that the global apoB100 N-glycan composition is invariable in the patient groups studied. 11588155 3 59 theme complex 796:802 arg1 N-glycans 816:824 truncated complex biantennary N-glycans 786:824 truncated complex biantennary N-glycans 786:824 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 7 60 theme abundant 1335:1342 arg1 alpha-N-acetylneuraminyllactosyl-ceramide 1361:1401 alpha-N-acetylneuraminyllactosyl-ceramide 1361:1401 alpha-N-acetylneuraminyllactosyl-ceramide 1361:1401 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and in the most buoyant subpopulation. 11588155 7 60 theme abundant 1335:1342 arg1 ganglioside 1348:1358 the most abundant LDL ganglioside 1326:1358 the most abundant LDL ganglioside 1326:1358 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and in the most buoyant subpopulation. 11588155 1 61 theme atherogenic 347:357 arg1 properties 359:368 the atherogenic properties 343:368 the atherogenic properties of low-density lipoprotein (LDL) 343:401 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 0 62 theme dense 205:209 arg1 particles 215:223 small dense LDL particles 199:223 small dense LDL particles 199:223 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 3 63 theme biantennary 804:814 arg1 N-glycans 816:824 truncated complex biantennary N-glycans 786:824 truncated complex biantennary N-glycans 786:824 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 5 64 dep derived 990:996 arg1 LDL1 1028:1031 LDL1 1028:1031 LDL1 1028:1031 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 64 dep derived 990:996 arg1 apoB100 982:988 apoB100 982:988 apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) 982:1146 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 5 65 theme = 1105:1105 arg1 d 1103:1103 d = 1.040-1.051 1103:1117 d = 1.040-1.051 1103:1117 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 7 66 theme buoyant 1461:1467 arg1 subpopulation 1469:1481 the most buoyant subpopulation 1452:1481 the most buoyant subpopulation 1452:1481 Analysis of the most abundant LDL ganglioside, alpha-N-acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and in the most buoyant subpopulation. 11588155 0 67 theme small 199:203 arg1 particles 215:223 small dense LDL particles 199:223 small dense LDL particles 199:223 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 5 68 theme d 1126:1126 arg1 g/ml 1142:1145 d = 1.051-1.065 g/ml 1126:1145 d = 1.051-1.065 g/ml 1126:1145 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 6 69 theme apoB100 1266:1272 arg1 glycans 1274:1280 "desialylated" apoB100 glycans 1251:1280 "desialylated" apoB100 glycans 1251:1280 Furthermore, we found no evidence for "desialylated" apoB100 glycans in any of the samples analyzed. 11588155 3 70 theme exoglycosidase 537:550 arg1 sequencing 565:574 exoglycosidase carbohydrate sequencing 537:574 exoglycosidase carbohydrate sequencing 537:574 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 1 71 theme apo 274:276 arg1 B100 279:282 apolipoprotein (apo) B100 258:282 apolipoprotein (apo) B100 258:282 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 1 71 theme apo 274:276 arg1 degree 302:307 particularly its degree 285:307 particularly its degree of sialylation 285:322 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 3 72 theme truncated 786:794 arg1 N-glycans 816:824 truncated complex biantennary N-glycans 786:824 truncated complex biantennary N-glycans 786:824 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 3 73 theme several 716:722 arg1 carbohydrates 724:736 several carbohydrates 716:736 several carbohydrates 716:736 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 3 73 theme several 716:722 arg1 N-glycans 816:824 truncated complex biantennary N-glycans 786:824 truncated complex biantennary N-glycans 786:824 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 3 73 theme several 716:722 arg1 N-glycans 837:845 hybrid N-glycans 830:845 hybrid N-glycans 830:845 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 2 74 theme normolipidemic 449:462 arg1 subjects 521:528 normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 449:528 normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 449:528 We analyzed LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects. 11588155 3 75 theme laser 596:600 arg1 spectrometry 629:640 matrix-assisted laser desorption/ionization mass spectrometry 580:640 matrix-assisted laser desorption/ionization mass spectrometry 580:640 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 5 76 theme LDL 1008:1010 arg1 subpopulations 1012:1025 five LDL subpopulations 1003:1025 five LDL subpopulations 1003:1025 The N-glycan composition of apoB100 derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023-1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml) did not vary in normolipidemic or hypercholesterolemic subjects. 11588155 2 77 theme diabetic 512:519 arg1 subjects 521:528 normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 449:528 normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects 449:528 We analyzed LDL apoB100 glycans derived from normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects. 11588155 3 78 theme hybrid 830:835 arg1 N-glycans 837:845 hybrid N-glycans 830:845 hybrid N-glycans 830:845 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 1 79 theme B100 279:282 arg1 composition 243:253 The carbohydrate composition 226:253 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, 226:323 The carbohydrate composition of apolipoprotein (apo) B100, particularly its degree of sialylation, may contribute to the atherogenic properties of low-density lipoprotein (LDL). 11588155 3 80 theme desorption/ionization 602:622 arg1 spectrometry 629:640 matrix-assisted laser desorption/ionization mass spectrometry 580:640 matrix-assisted laser desorption/ionization mass spectrometry 580:640 Using exoglycosidase carbohydrate sequencing and matrix-assisted laser desorption/ionization mass spectrometry to analyze fluorescently labeled oligosaccharides, we report evidence for several carbohydrates not previously identified on apoB100, including truncated complex biantennary N-glycans and hybrid N-glycans. 11588155 0 81 from deficiency 130:139 arg1 particles 215:223 small dense LDL particles 199:223 small dense LDL particles 199:223 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 11588155 0 81 from deficiency 130:139 arg1 light 189:193 light 189:193 light 189:193 Characterization of human apolipoprotein B100 oligosaccharides in LDL subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N-acetylneuraminyllactosyl-ceramide in light and small dense LDL particles. 9760189 3 0 theme intact 289:294 arg1 chains 309:314 The intact carbohydrate chains 285:314 The intact carbohydrate chains 285:314 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 3 1 from Q 380:380 arg1 LiChrosorb-NH2 391:404 LiChrosorb-NH2 391:404 LiChrosorb-NH2 391:404 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 3 1 from Q 380:380 arg1 PA-1 461:464 CarboPac PA-1 452:464 CarboPac PA-1 452:464 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 5 2 theme trisulfated 653:663 arg1 N-glycans 665:673 trisulfated N-glycans 653:673 trisulfated N-glycans 653:673 The type of characterized N-glycans ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). 9760189 1 3 theme tetraantennary 137:150 arg1 N-glycans 152:160 32 sulfated di-, tri- and tetraantennary N-glycans 111:160 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) 111:202 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 3 4 theme carbohydrate 296:307 arg1 chains 309:314 The intact carbohydrate chains 285:314 The intact carbohydrate chains 285:314 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 4 5 theme 500-MHz 506:512 arg1 spectroscopy 533:544 500-MHz and 600-MHz 1H-NMR spectroscopy 506:544 spectroscopy 533:544 Characterizations were performed using 500-MHz and 600-MHz 1H-NMR spectroscopy, in combination with sialidase treatments. 9760189 6 6 theme structures 813:822 arg1 compilation 782:792 A compilation 780:792 A compilation of the established structures 780:822 A compilation of the established structures is shown below. 9760189 1 7 theme N-glycans 152:160 arg1 structures 97:106 The primary structures 85:106 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) 85:202 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 4 8 theme sialidase 567:575 arg1 treatments 577:586 sialidase treatments 567:586 sialidase treatments 567:586 Characterizations were performed using 500-MHz and 600-MHz 1H-NMR spectroscopy, in combination with sialidase treatments. 9760189 3 9 from HPLC 383:386 arg1 LiChrosorb-NH2 391:404 LiChrosorb-NH2 391:404 LiChrosorb-NH2 391:404 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 3 9 from HPLC 383:386 arg1 PA-1 461:464 CarboPac PA-1 452:464 CarboPac PA-1 452:464 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 1 10 gly glycoprotein 185:196 arg1 THP 199:201 THP 199:201 THP 199:201 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 1 10 gly glycoprotein 185:196 arg1 glycoprotein 185:196 human Tamm-Horsfall glycoprotein 165:196 human Tamm-Horsfall glycoprotein (THP) 165:202 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 6 11 theme established 801:811 arg1 structures 813:822 the established structures 797:822 the established structures 797:822 A compilation of the established structures is shown below. 9760189 2 12 theme healthy 265:271 arg1 donor 278:282 one healthy male donor 261:282 one healthy male donor 261:282 THP was isolated from the urine of one healthy male donor. 9760189 5 13 theme characterized 601:613 arg1 N-glycans 615:623 characterized N-glycans 601:623 characterized N-glycans 601:623 The type of characterized N-glycans ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). 9760189 4 14 with combination 550:560 arg1 treatments 577:586 sialidase treatments 567:586 sialidase treatments 567:586 Characterizations were performed using 500-MHz and 600-MHz 1H-NMR spectroscopy, in combination with sialidase treatments. 9760189 0 15 from N-glycans 38:46 arg1 glycoprotein 71:82 human Tamm-Horsfall glycoprotein 51:82 human Tamm-Horsfall glycoprotein 51:82 Sulfated di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein. 9760189 5 16 theme N-glycans 615:623 arg1 type 593:596 The type 589:596 The type of characterized N-glycans 589:623 The type of characterized N-glycans ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). 9760189 0 17 gly glycoprotein 71:82 arg1 glycoprotein 71:82 human Tamm-Horsfall glycoprotein 51:82 human Tamm-Horsfall glycoprotein 51:82 Sulfated di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein. 9760189 1 18 theme human 165:169 arg1 THP 199:201 THP 199:201 THP 199:201 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 1 18 theme human 165:169 arg1 glycoprotein 185:196 human Tamm-Horsfall glycoprotein 165:196 human Tamm-Horsfall glycoprotein (THP) 165:202 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 0 19 theme di- 9:11 arg1 N-glycans 38:46 di-, tri- and tetraantennary N-glycans 9:46 di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein 9:82 Sulfated di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein. 9760189 5 20 theme 4-O-sulfated 748:759 arg1 GalNAc 761:766 4-O-sulfated GalNAc 748:766 4-O-sulfated GalNAc (GalNAc4S) 748:777 The type of characterized N-glycans ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). 9760189 5 20 theme 4-O-sulfated 748:759 arg1 GalNAc4S 769:776 GalNAc4S 769:776 GalNAc4S 769:776 The type of characterized N-glycans ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). 9760189 1 21 theme Tamm-Horsfall 171:183 arg1 THP 199:201 THP 199:201 THP 199:201 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 1 21 theme Tamm-Horsfall 171:183 arg1 glycoprotein 185:196 human Tamm-Horsfall glycoprotein 165:196 human Tamm-Horsfall glycoprotein (THP) 165:202 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 1 22 theme primary 89:95 arg1 structures 97:106 The primary structures 85:106 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) 85:202 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 1 23 theme glycoprotein 185:196 arg1 N-glycans 152:160 32 sulfated di-, tri- and tetraantennary N-glycans 111:160 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) 111:202 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 0 24 theme tri- 14:17 arg1 N-glycans 38:46 di-, tri- and tetraantennary N-glycans 9:46 di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein 9:82 Sulfated di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein. 9760189 2 25 theme donor 278:282 arg1 urine 252:256 the urine 248:256 the urine of one healthy male donor 248:282 THP was isolated from the urine of one healthy male donor. 9760189 2 26 theme male 273:276 arg1 donor 278:282 one healthy male donor 261:282 one healthy male donor 261:282 THP was isolated from the urine of one healthy male donor. 9760189 0 27 theme tetraantennary 23:36 arg1 N-glycans 38:46 di-, tri- and tetraantennary N-glycans 9:46 di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein 9:82 Sulfated di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein. 9760189 5 28 theme 3-O-sulfated 719:730 arg1 Gal3S 737:741 Gal3S 737:741 Gal3S 737:741 The type of characterized N-glycans ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). 9760189 5 28 theme 3-O-sulfated 719:730 arg1 Gal 732:734 3-O-sulfated Gal 719:734 3-O-sulfated Gal (Gal3S) 719:742 The type of characterized N-glycans ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). 9760189 3 29 theme high-pH 411:417 arg1 chromatography 434:447 high-pH anion-exchange chromatography 411:447 high-pH anion-exchange chromatography on CarboPac PA-1 411:464 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 4 30 theme 600-MHz 518:524 arg1 spectroscopy 533:544 500-MHz and 600-MHz 1H-NMR spectroscopy 506:544 spectroscopy 533:544 Characterizations were performed using 500-MHz and 600-MHz 1H-NMR spectroscopy, in combination with sialidase treatments. 9760189 3 31 theme anion-exchange 419:432 arg1 chromatography 434:447 high-pH anion-exchange chromatography 411:447 high-pH anion-exchange chromatography on CarboPac PA-1 411:464 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 3 32 theme Resource 371:378 arg1 Q 380:380 Resource Q 371:380 Resource Q 371:380 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 5 33 theme sulfate 688:694 arg1 groups 696:701 the sulfate groups 684:701 the sulfate groups 684:701 The type of characterized N-glycans ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). 9760189 5 33 theme sulfate 688:694 arg1 present 708:714 present 708:714 present 708:714 The type of characterized N-glycans ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). 9760189 3 34 from chromatography 434:447 arg1 LiChrosorb-NH2 391:404 LiChrosorb-NH2 391:404 LiChrosorb-NH2 391:404 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 3 34 from chromatography 434:447 arg1 PA-1 461:464 CarboPac PA-1 452:464 CarboPac PA-1 452:464 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 1 35 theme sulfated 114:121 arg1 N-glycans 152:160 32 sulfated di-, tri- and tetraantennary N-glycans 111:160 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) 111:202 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 4 36 theme 1H-NMR 526:531 arg1 spectroscopy 533:544 500-MHz and 600-MHz 1H-NMR spectroscopy 506:544 spectroscopy 533:544 Characterizations were performed using 500-MHz and 600-MHz 1H-NMR spectroscopy, in combination with sialidase treatments. 9760189 7 37 from [structure 840:849 arg1 text 854:857 text 854:857 text 854:857 [structure in text] 9760189 1 38 theme di- 123:125 arg1 N-glycans 152:160 32 sulfated di-, tri- and tetraantennary N-glycans 111:160 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) 111:202 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 3 39 theme CarboPac 452:459 arg1 PA-1 461:464 CarboPac PA-1 452:464 CarboPac PA-1 452:464 The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. 9760189 0 40 theme Tamm-Horsfall 57:69 arg1 glycoprotein 71:82 human Tamm-Horsfall glycoprotein 51:82 human Tamm-Horsfall glycoprotein 51:82 Sulfated di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein. 9760189 1 41 theme tri- 128:131 arg1 N-glycans 152:160 32 sulfated di-, tri- and tetraantennary N-glycans 111:160 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) 111:202 The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. 9760189 0 42 theme human 51:55 arg1 glycoprotein 71:82 human Tamm-Horsfall glycoprotein 51:82 human Tamm-Horsfall glycoprotein 51:82 Sulfated di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein. 9760189 2 43 attach isolated 234:241 arg1 urine 252:256 the urine 248:256 the urine of one healthy male donor 248:282 THP was isolated from the urine of one healthy male donor. 9760189 2 43 attach isolated 234:241 arg2 THP 226:228 THP 226:228 THP 226:228 THP was isolated from the urine of one healthy male donor. 8026573 0 0 theme carbohydrate 66:77 arg1 chains 79:84 the carbohydrate chains 62:84 the carbohydrate chains of an intact glycoprotein 62:110 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein. 8026573 4 1 theme pulsed 522:527 arg1 gradients 535:543 pulsed field gradients 522:543 pulsed field gradients 522:543 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 5 2 theme alpha 808:812 arg1 region 814:819 the protein C alpha-H alpha region 786:819 the protein C alpha-H alpha region 786:819 Most carbohydrate 1H-13C correlations appear in a distinct region between the aromatic region and the protein C alpha-H alpha region. 8026573 1 3 theme abundance 154:162 arg1 Application 113:123 Application 113:123 Application of gradient-enhanced natural abundance 113:162 Application of gradient-enhanced natural abundance 1H-13C HSQC and HSQC-TOCSY to the alpha-subunit of human chorionic gonadotropin. 8026573 5 4 theme protein 790:796 arg1 region 814:819 the protein C alpha-H alpha region 786:819 the protein C alpha-H alpha region 786:819 Most carbohydrate 1H-13C correlations appear in a distinct region between the aromatic region and the protein C alpha-H alpha region. 8026573 5 5 theme carbohydrate 693:704 arg1 correlations 713:724 Most carbohydrate 1H-13C correlations 688:724 Most carbohydrate 1H-13C correlations 688:724 Most carbohydrate 1H-13C correlations appear in a distinct region between the aromatic region and the protein C alpha-H alpha region. 8026573 2 6 theme resonances 365:374 arg1 assignment 330:339 an extensive assignment 317:339 an extensive assignment of the carbohydrate NMR resonances 317:374 The structure assessment of an intact glycoprotein in solution requires an extensive assignment of the carbohydrate NMR resonances. 8026573 5 7 theme Most 688:691 arg1 correlations 713:724 Most carbohydrate 1H-13C correlations 688:724 Most carbohydrate 1H-13C correlations 688:724 Most carbohydrate 1H-13C correlations appear in a distinct region between the aromatic region and the protein C alpha-H alpha region. 8026573 4 8 theme gradients 535:543 arg1 Application 507:517 Application 507:517 Application of pulsed field gradients 507:543 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 5 9 theme 1H-13C 706:711 arg1 correlations 713:724 Most carbohydrate 1H-13C correlations 688:724 Most carbohydrate 1H-13C correlations 688:724 Most carbohydrate 1H-13C correlations appear in a distinct region between the aromatic region and the protein C alpha-H alpha region. 8026573 3 10 theme spectra 412:418 arg1 assignment 386:395 assignment 386:395 assignment of homonuclear spectra 386:418 However, assignment of homonuclear spectra is very complicated because of the severe overlap of protein and carbohydrate signals. 8026573 0 11 theme chains 79:84 arg1 assignment 48:57 the NMR resonance assignment 30:57 the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein 30:110 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein. 8026573 0 12 theme intact 92:97 arg1 glycoprotein 99:110 an intact glycoprotein 89:110 an intact glycoprotein 89:110 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein. 8026573 0 13 gly glycoprotein 99:110 arg1 glycoprotein 99:110 an intact glycoprotein 89:110 an intact glycoprotein 89:110 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein. 8026573 4 14 theme human 658:662 arg1 gonadotropin 674:685 human chorionic gonadotropin 658:685 human chorionic gonadotropin 658:685 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 2 15 theme glycoprotein 283:294 arg1 assessment 259:268 The structure assessment 245:268 The structure assessment of an intact glycoprotein in solution 245:306 The structure assessment of an intact glycoprotein in solution requires an extensive assignment of the carbohydrate NMR resonances. 8026573 2 16 gly glycoprotein 283:294 arg1 glycoprotein 283:294 an intact glycoprotein 273:294 an intact glycoprotein 273:294 The structure assessment of an intact glycoprotein in solution requires an extensive assignment of the carbohydrate NMR resonances. 8026573 2 17 theme intact 276:281 arg1 glycoprotein 283:294 an intact glycoprotein 273:294 an intact glycoprotein 273:294 The structure assessment of an intact glycoprotein in solution requires an extensive assignment of the carbohydrate NMR resonances. 8026573 3 18 theme homonuclear 400:410 arg1 spectra 412:418 homonuclear spectra 400:418 homonuclear spectra 400:418 However, assignment of homonuclear spectra is very complicated because of the severe overlap of protein and carbohydrate signals. 8026573 6 19 theme correlations 918:929 arg1 assignment 884:893 fast and unambiguous assignment 863:893 fast and unambiguous assignment of the anomeric 1H-13C correlations 863:929 The enormous reduction in overlap led to fast and unambiguous assignment of the anomeric 1H-13C correlations. 8026573 6 20 theme enormous 826:833 arg1 reduction 835:843 The enormous reduction 822:843 The enormous reduction in overlap 822:854 The enormous reduction in overlap led to fast and unambiguous assignment of the anomeric 1H-13C correlations. 8026573 0 21 theme Rapid 0:4 arg1 approach 17:24 Rapid and simple approach 0:24 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein 0:110 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein. 8026573 6 22 theme fast 863:866 arg1 assignment 884:893 fast and unambiguous assignment 863:893 fast and unambiguous assignment of the anomeric 1H-13C correlations 863:929 The enormous reduction in overlap led to fast and unambiguous assignment of the anomeric 1H-13C correlations. 8026573 7 23 theme skeleton 981:988 arg1 atoms 990:994 the monosaccharide skeleton atoms 962:994 the monosaccharide skeleton atoms 962:994 Subsequently, correlations of the monosaccharide skeleton atoms were readily assigned in the HSQC-TOCSY spectrum. 8026573 2 24 theme extensive 320:328 arg1 assignment 330:339 an extensive assignment 317:339 an extensive assignment of the carbohydrate NMR resonances 317:374 The structure assessment of an intact glycoprotein in solution requires an extensive assignment of the carbohydrate NMR resonances. 8026573 2 25 from assessment 259:268 arg1 solution 299:306 solution 299:306 solution 299:306 The structure assessment of an intact glycoprotein in solution requires an extensive assignment of the carbohydrate NMR resonances. 8026573 4 26 theme 1H-13C 584:589 arg1 HSQC 591:594 high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra 553:617 HSQC 591:594 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 7 27 theme atoms 990:994 arg1 correlations 946:957 correlations 946:957 correlations of the monosaccharide skeleton atoms 946:994 Subsequently, correlations of the monosaccharide skeleton atoms were readily assigned in the HSQC-TOCSY spectrum. 8026573 4 28 theme chorionic 664:672 arg1 gonadotropin 674:685 human chorionic gonadotropin 658:685 human chorionic gonadotropin 658:685 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 0 29 theme simple 10:15 arg1 approach 17:24 Rapid and simple approach 0:24 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein 0:110 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein. 8026573 4 30 theme HSQC-TOCSY 600:609 arg1 spectra 611:617 high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra 553:617 spectra 611:617 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 0 31 theme glycoprotein 99:110 arg1 chains 79:84 the carbohydrate chains 62:84 the carbohydrate chains of an intact glycoprotein 62:110 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein. 8026573 6 32 theme 1H-13C 911:916 arg1 correlations 918:929 the anomeric 1H-13C correlations 898:929 the anomeric 1H-13C correlations 898:929 The enormous reduction in overlap led to fast and unambiguous assignment of the anomeric 1H-13C correlations. 8026573 3 33 theme carbohydrate 485:496 arg1 severe 455:460 severe 455:460 severe 455:460 However, assignment of homonuclear spectra is very complicated because of the severe overlap of protein and carbohydrate signals. 8026573 6 34 theme anomeric 902:909 arg1 correlations 918:929 the anomeric 1H-13C correlations 898:929 the anomeric 1H-13C correlations 898:929 The enormous reduction in overlap led to fast and unambiguous assignment of the anomeric 1H-13C correlations. 8026573 4 35 theme gonadotropin 674:685 arg1 alpha-subunit 641:653 the alpha-subunit 637:653 the alpha-subunit of human chorionic gonadotropin 637:685 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 6 36 from reduction 835:843 arg1 overlap 848:854 overlap 848:854 overlap 848:854 The enormous reduction in overlap led to fast and unambiguous assignment of the anomeric 1H-13C correlations. 8026573 4 37 theme quality 558:564 arg1 HSQC 591:594 high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra 553:617 HSQC 591:594 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 5 38 theme aromatic 766:773 arg1 region 775:780 the aromatic region 762:780 the aromatic region 762:780 Most carbohydrate 1H-13C correlations appear in a distinct region between the aromatic region and the protein C alpha-H alpha region. 8026573 1 39 theme human 215:219 arg1 gonadotropin 231:242 human chorionic gonadotropin 215:242 human chorionic gonadotropin 215:242 Application of gradient-enhanced natural abundance 1H-13C HSQC and HSQC-TOCSY to the alpha-subunit of human chorionic gonadotropin. 8026573 0 40 theme resonance 38:46 arg1 assignment 48:57 the NMR resonance assignment 30:57 the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein 30:110 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein. 8026573 4 41 theme high 553:556 arg1 HSQC 591:594 high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra 553:617 HSQC 591:594 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 3 42 dep severe 455:460 arg1 overlap 462:468 overlap 462:468 overlap 462:468 However, assignment of homonuclear spectra is very complicated because of the severe overlap of protein and carbohydrate signals. 8026573 2 43 theme NMR 361:363 arg1 resonances 365:374 the carbohydrate NMR resonances 344:374 the carbohydrate NMR resonances 344:374 The structure assessment of an intact glycoprotein in solution requires an extensive assignment of the carbohydrate NMR resonances. 8026573 0 44 theme NMR 34:36 arg1 assignment 48:57 the NMR resonance assignment 30:57 the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein 30:110 Rapid and simple approach for the NMR resonance assignment of the carbohydrate chains of an intact glycoprotein. 8026573 4 45 theme abundance 574:582 arg1 HSQC 591:594 high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra 553:617 HSQC 591:594 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 2 46 theme carbohydrate 348:359 arg1 resonances 365:374 the carbohydrate NMR resonances 344:374 the carbohydrate NMR resonances 344:374 The structure assessment of an intact glycoprotein in solution requires an extensive assignment of the carbohydrate NMR resonances. 8026573 4 47 theme natural 566:572 arg1 HSQC 591:594 high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra 553:617 HSQC 591:594 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 6 48 theme unambiguous 872:882 arg1 assignment 884:893 fast and unambiguous assignment 863:893 fast and unambiguous assignment of the anomeric 1H-13C correlations 863:929 The enormous reduction in overlap led to fast and unambiguous assignment of the anomeric 1H-13C correlations. 8026573 7 49 theme HSQC-TOCSY 1025:1034 arg1 spectrum 1036:1043 the HSQC-TOCSY spectrum 1021:1043 the HSQC-TOCSY spectrum 1021:1043 Subsequently, correlations of the monosaccharide skeleton atoms were readily assigned in the HSQC-TOCSY spectrum. 8026573 7 50 theme monosaccharide 966:979 arg1 atoms 990:994 the monosaccharide skeleton atoms 962:994 the monosaccharide skeleton atoms 962:994 Subsequently, correlations of the monosaccharide skeleton atoms were readily assigned in the HSQC-TOCSY spectrum. 8026573 1 51 theme chorionic 221:229 arg1 gonadotropin 231:242 human chorionic gonadotropin 215:242 human chorionic gonadotropin 215:242 Application of gradient-enhanced natural abundance 1H-13C HSQC and HSQC-TOCSY to the alpha-subunit of human chorionic gonadotropin. 8026573 5 52 theme distinct 738:745 arg1 region 747:752 a distinct region 736:752 a distinct region between the aromatic region and the protein C alpha-H alpha region 736:819 Most carbohydrate 1H-13C correlations appear in a distinct region between the aromatic region and the protein C alpha-H alpha region. 8026573 3 53 dep protein 473:479 arg1 signals 498:504 signals 498:504 signals 498:504 However, assignment of homonuclear spectra is very complicated because of the severe overlap of protein and carbohydrate signals. 8026573 1 54 theme gonadotropin 231:242 arg1 alpha-subunit 198:210 the alpha-subunit 194:210 the alpha-subunit of human chorionic gonadotropin 194:242 Application of gradient-enhanced natural abundance 1H-13C HSQC and HSQC-TOCSY to the alpha-subunit of human chorionic gonadotropin. 8026573 5 55 theme C 798:798 arg1 region 814:819 the protein C alpha-H alpha region 786:819 the protein C alpha-H alpha region 786:819 Most carbohydrate 1H-13C correlations appear in a distinct region between the aromatic region and the protein C alpha-H alpha region. 8026573 3 56 theme protein 473:479 arg1 severe 455:460 severe 455:460 severe 455:460 However, assignment of homonuclear spectra is very complicated because of the severe overlap of protein and carbohydrate signals. 8026573 1 57 theme gradient-enhanced 128:144 arg1 abundance 154:162 gradient-enhanced natural abundance 128:162 gradient-enhanced natural abundance 128:162 Application of gradient-enhanced natural abundance 1H-13C HSQC and HSQC-TOCSY to the alpha-subunit of human chorionic gonadotropin. 8026573 5 58 theme alpha-H 800:806 arg1 region 814:819 the protein C alpha-H alpha region 786:819 the protein C alpha-H alpha region 786:819 Most carbohydrate 1H-13C correlations appear in a distinct region between the aromatic region and the protein C alpha-H alpha region. 8026573 4 59 theme field 529:533 arg1 gradients 535:543 pulsed field gradients 522:543 pulsed field gradients 522:543 Application of pulsed field gradients allowed high quality natural abundance 1H-13C HSQC and HSQC-TOCSY spectra to be recorded of the alpha-subunit of human chorionic gonadotropin. 8026573 2 60 theme structure 249:257 arg1 assessment 259:268 The structure assessment 245:268 The structure assessment of an intact glycoprotein in solution 245:306 The structure assessment of an intact glycoprotein in solution requires an extensive assignment of the carbohydrate NMR resonances. 8026573 1 61 theme natural 146:152 arg1 abundance 154:162 gradient-enhanced natural abundance 128:162 gradient-enhanced natural abundance 128:162 Application of gradient-enhanced natural abundance 1H-13C HSQC and HSQC-TOCSY to the alpha-subunit of human chorionic gonadotropin. 8251489 5 0 with digestion 646:654 arg1 sialidase 661:669 sialidase 661:669 sialidase 661:669 All of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. 8251489 8 1 theme tetraantennary 1233:1246 arg1 chains 1267:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 2 2 from CD45 319:322 arg1 oligosaccharides 288:303 oligosaccharides 288:303 oligosaccharides from purified CD45 288:322 The asparagine-linked sugar chains were released as oligosaccharides from purified CD45 by hydrazinolysis. 8251489 2 2 from CD45 319:322 arg1 chains 264:269 The asparagine-linked sugar chains 236:269 The asparagine-linked sugar chains 236:269 The asparagine-linked sugar chains were released as oligosaccharides from purified CD45 by hydrazinolysis. 8251489 11 3 theme small 1613:1617 arg1 chains 1669:1674 hybrid-type sugar chains 1651:1674 hybrid-type sugar chains 1651:1674 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 11 3 theme small 1613:1617 arg1 amount 1619:1624 a small amount 1611:1624 a small amount of high mannose-type and hybrid-type sugar chains 1611:1674 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 11 3 theme small 1613:1617 arg1 mannose-type 1634:1645 high mannose-type 1629:1645 high mannose-type 1629:1645 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 8 4 theme sugar 1261:1265 arg1 chains 1267:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 5 5 theme neutral 630:636 arg1 ones 638:641 neutral ones 630:641 neutral ones 630:641 All of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. 8251489 6 6 theme methylation 796:806 arg1 analysis 808:815 methylation analysis 796:815 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis 717:815 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 2 7 theme sugar 258:262 arg1 oligosaccharides 288:303 oligosaccharides 288:303 oligosaccharides from purified CD45 288:322 The asparagine-linked sugar chains were released as oligosaccharides from purified CD45 by hydrazinolysis. 8251489 2 7 theme sugar 258:262 arg1 chains 264:269 The asparagine-linked sugar chains 236:269 The asparagine-linked sugar chains 236:269 The asparagine-linked sugar chains were released as oligosaccharides from purified CD45 by hydrazinolysis. 8251489 8 8 theme Structural 1063:1072 arg1 studies 1074:1080 Structural studies 1063:1080 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis 1063:1181 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 11 9 theme mannose-type 1634:1645 arg1 chains 1669:1674 hybrid-type sugar chains 1651:1674 hybrid-type sugar chains 1651:1674 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 11 9 theme mannose-type 1634:1645 arg1 amount 1619:1624 a small amount 1611:1624 a small amount of high mannose-type and hybrid-type sugar chains 1611:1674 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 11 9 theme mannose-type 1634:1645 arg1 mannose-type 1634:1645 high mannose-type 1629:1645 high mannose-type 1629:1645 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 9 10 theme complex-type 1307:1318 arg1 chains 1326:1331 the tetraantennary complex-type sugar chains 1288:1331 the tetraantennary complex-type sugar chains 1288:1331 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 9 11 theme chains 1326:1331 arg1 chains 1326:1331 the tetraantennary complex-type sugar chains 1288:1331 the tetraantennary complex-type sugar chains 1288:1331 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 9 11 theme chains 1326:1331 arg1 % 1283:1283 About 46% 1275:1283 About 46% of the tetraantennary complex-type sugar chains 1275:1331 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 1 12 theme glycoprotein 104:115 arg1 CD45 117:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 1 12 theme glycoprotein 104:115 arg1 phosphatase 144:154 a protein tyrosine phosphatase 125:154 a protein tyrosine phosphatase 125:154 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 0 13 theme leukocyte 46:54 arg1 CD45 71:74 human leukocyte common antigen CD45 40:74 human leukocyte common antigen CD45 40:74 Structural study of the sugar chains of human leukocyte common antigen CD45. 8251489 7 14 theme P-4 1036:1038 arg1 chromatography 1047:1060 Bio-Gel P-4 column chromatography 1028:1060 Bio-Gel P-4 column chromatography 1028:1060 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 8251489 1 15 theme protein 127:133 arg1 CD45 117:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 1 15 theme protein 127:133 arg1 phosphatase 144:154 a protein tyrosine phosphatase 125:154 a protein tyrosine phosphatase 125:154 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 10 16 theme sugar 1548:1552 arg1 chains 1554:1559 the bi- and 2,4-branched triantennary complex-type sugar chains 1497:1559 the bi- and 2,4-branched triantennary complex-type sugar chains 1497:1559 A portion of the bi- and 2,4-branched triantennary complex-type sugar chains were bisected. 8251489 0 17 theme antigen 63:69 arg1 CD45 71:74 human leukocyte common antigen CD45 40:74 human leukocyte common antigen CD45 40:74 Structural study of the sugar chains of human leukocyte common antigen CD45. 8251489 8 18 theme oligosaccharide 1090:1104 arg1 studies 1074:1080 Structural studies 1063:1080 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis 1063:1181 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 5 19 theme acidic 588:593 arg1 oligosaccharides 595:610 the acidic oligosaccharides 584:610 the acidic oligosaccharides 584:610 All of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. 8251489 10 20 theme triantennary 1522:1533 arg1 chains 1554:1559 the bi- and 2,4-branched triantennary complex-type sugar chains 1497:1559 the bi- and 2,4-branched triantennary complex-type sugar chains 1497:1559 A portion of the bi- and 2,4-branched triantennary complex-type sugar chains were bisected. 8251489 2 21 link asparagine-linked 240:256 arg1 oligosaccharides 288:303 oligosaccharides 288:303 oligosaccharides from purified CD45 288:322 The asparagine-linked sugar chains were released as oligosaccharides from purified CD45 by hydrazinolysis. 8251489 2 21 link asparagine-linked 240:256 arg1 chains 264:269 The asparagine-linked sugar chains 236:269 The asparagine-linked sugar chains 236:269 The asparagine-linked sugar chains were released as oligosaccharides from purified CD45 by hydrazinolysis. 8251489 8 22 theme sequential 1109:1118 arg1 exo- 1120:1123 sequential exo- 1109:1123 sequential exo- 1109:1123 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 4 23 theme radioactive 449:459 arg1 oligosaccharides 461:476 radioactive oligosaccharides 449:476 radioactive oligosaccharides 449:476 These sugar chains were converted to radioactive oligosaccharides by reduction with NaB3H4 and separated into neutral and acidic fractions by paper electrophoresis. 8251489 7 24 theme lectin 987:992 arg1 chromatography 1001:1014 serial lectin column chromatography 980:1014 serial lectin column chromatography followed by Bio-Gel P-4 column chromatography 980:1060 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 8251489 3 25 theme CD45 406:409 arg1 mol 399:401 1 mol 397:401 1 mol of CD45 397:409 Approximately 6 mol of sugar chains was released from 1 mol of CD45. 8251489 0 26 theme Structural 0:9 arg1 study 11:15 Structural study 0:15 Structural study of the sugar chains of human leukocyte common antigen CD45. 0:75 Structural study of the sugar chains of human leukocyte common antigen CD45. 8251489 9 27 theme triantennary 1402:1413 arg1 chains 1434:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 3 28 theme sugar 366:370 arg1 chains 372:377 sugar chains 366:377 sugar chains 366:377 Approximately 6 mol of sugar chains was released from 1 mol of CD45. 8251489 9 29 theme sugar 1428:1432 arg1 chains 1434:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 1 30 theme cell 91:94 arg1 CD45 117:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 1 30 theme cell 91:94 arg1 phosphatase 144:154 a protein tyrosine phosphatase 125:154 a protein tyrosine phosphatase 125:154 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 4 31 theme paper 554:558 arg1 electrophoresis 560:574 paper electrophoresis 554:574 paper electrophoresis 554:574 These sugar chains were converted to radioactive oligosaccharides by reduction with NaB3H4 and separated into neutral and acidic fractions by paper electrophoresis. 8251489 0 32 theme sugar 24:28 arg1 chains 30:35 the sugar chains 20:35 the sugar chains of human leukocyte common antigen CD45 20:74 Structural study of the sugar chains of human leukocyte common antigen CD45. 8251489 6 33 theme acid 886:889 arg1 residues 891:898 only alpha-2,6-linked sialic acid residues 857:898 only alpha-2,6-linked sialic acid residues 857:898 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 6 34 theme SNA-agarose 766:776 arg1 column 778:783 an SNA-agarose column 763:783 an SNA-agarose column 763:783 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 8 35 contain contains 1202:1209 arg1 CD45 1197:1200 CD45 1197:1200 CD45 1197:1200 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 8 35 contain contains 1202:1209 arg2 chains 1267:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 9 36 theme fucosyl 1449:1455 arg1 group 1477:1481 the fucosyl N-acetyllactosamine group 1445:1481 the fucosyl N-acetyllactosamine group 1445:1481 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 6 37 theme alpha-2,6-linked 862:877 arg1 residues 891:898 only alpha-2,6-linked sialic acid residues 857:898 only alpha-2,6-linked sialic acid residues 857:898 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 11 38 theme hybrid-type 1651:1661 arg1 chains 1669:1674 hybrid-type sugar chains 1651:1674 hybrid-type sugar chains 1651:1674 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 6 39 theme sialylated 732:741 arg1 oligosaccharides 743:758 the sialylated oligosaccharides 728:758 the sialylated oligosaccharides 728:758 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 4 40 with reduction 481:489 arg1 NaB3H4 496:501 NaB3H4 496:501 NaB3H4 496:501 These sugar chains were converted to radioactive oligosaccharides by reduction with NaB3H4 and separated into neutral and acidic fractions by paper electrophoresis. 8251489 1 41 theme cell 213:216 arg1 receptor 226:233 the T cell antigen receptor 207:233 the T cell antigen receptor 207:233 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 8 42 theme bi- 1218:1220 arg1 chains 1267:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 9 43 contain had 1441:1443 arg2 group 1477:1481 the fucosyl N-acetyllactosamine group 1445:1481 the fucosyl N-acetyllactosamine group 1445:1481 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 9 43 contain had 1441:1443 arg1 chains 1434:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 9 43 contain had 1441:1443 arg1 % 1380:1380 18% 1378:1380 18% of the 2,4-branched triantennary complex-type sugar chains 1378:1439 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 6 44 link alpha-2,6-linked 862:877 arg1 residues 891:898 only alpha-2,6-linked sialic acid residues 857:898 only alpha-2,6-linked sialic acid residues 857:898 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 7 45 theme sialidase-treated 917:933 arg1 oligosaccharides 942:957 The neutral and sialidase-treated acidic oligosaccharides 901:957 The neutral and sialidase-treated acidic oligosaccharides 901:957 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 8251489 8 46 theme tri- 1223:1226 arg1 chains 1267:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 11 47 theme sugar 1663:1667 arg1 chains 1669:1674 hybrid-type sugar chains 1651:1674 hybrid-type sugar chains 1651:1674 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 11 48 theme high 1629:1632 arg1 mannose-type 1634:1645 high mannose-type 1629:1645 high mannose-type 1629:1645 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 7 49 theme neutral 905:911 arg1 oligosaccharides 942:957 The neutral and sialidase-treated acidic oligosaccharides 901:957 The neutral and sialidase-treated acidic oligosaccharides 901:957 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 8251489 8 50 theme complex-type 1248:1259 arg1 chains 1267:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 bi-, tri-, and tetraantennary complex-type sugar chains 1218:1272 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 10 51 theme bi- 1501:1503 arg1 chains 1554:1559 the bi- and 2,4-branched triantennary complex-type sugar chains 1497:1559 the bi- and 2,4-branched triantennary complex-type sugar chains 1497:1559 A portion of the bi- and 2,4-branched triantennary complex-type sugar chains were bisected. 8251489 2 52 theme purified 310:317 arg1 CD45 319:322 purified CD45 310:322 purified CD45 310:322 The asparagine-linked sugar chains were released as oligosaccharides from purified CD45 by hydrazinolysis. 8251489 1 53 gly glycoprotein 104:115 arg1 glycoprotein 104:115 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 9 54 theme tetraantennary 1292:1305 arg1 chains 1326:1331 the tetraantennary complex-type sugar chains 1288:1331 the tetraantennary complex-type sugar chains 1288:1331 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 1 55 theme signal 175:180 arg1 transduction 182:193 signal transduction 175:193 signal transduction mediated by the T cell antigen receptor 175:233 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 9 56 theme sugar 1320:1324 arg1 chains 1326:1331 the tetraantennary complex-type sugar chains 1288:1331 the tetraantennary complex-type sugar chains 1288:1331 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 1 57 theme surface 96:102 arg1 CD45 117:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 1 57 theme surface 96:102 arg1 phosphatase 144:154 a protein tyrosine phosphatase 125:154 a protein tyrosine phosphatase 125:154 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 5 58 theme sialyl 697:702 arg1 they 688:691 they 688:691 they 688:691 All of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. 8251489 5 58 theme sialyl 697:702 arg1 derivatives 704:714 sialyl derivatives 697:714 sialyl derivatives 697:714 All of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. 8251489 3 59 attach released 383:390 arg2 mol 359:361 Approximately 6 mol 343:361 Approximately 6 mol of sugar chains 343:377 Approximately 6 mol of sugar chains was released from 1 mol of CD45. 8251489 3 59 attach released 383:390 arg1 mol 399:401 1 mol 397:401 1 mol of CD45 397:409 Approximately 6 mol of sugar chains was released from 1 mol of CD45. 8251489 9 60 contain had 1333:1335 arg1 chains 1326:1331 the tetraantennary complex-type sugar chains 1288:1331 the tetraantennary complex-type sugar chains 1288:1331 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 9 60 contain had 1333:1335 arg2 groups 1367:1372 the poly(N-acetyllactosamine) groups 1337:1372 the poly(N-acetyllactosamine) groups 1337:1372 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 9 60 contain had 1333:1335 arg1 % 1283:1283 About 46% 1275:1283 About 46% of the tetraantennary complex-type sugar chains 1275:1331 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 9 61 theme poly 1341:1344 arg1 groups 1367:1372 the poly(N-acetyllactosamine) groups 1337:1372 the poly(N-acetyllactosamine) groups 1337:1372 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 2 62 theme asparagine-linked 240:256 arg1 oligosaccharides 288:303 oligosaccharides 288:303 oligosaccharides from purified CD45 288:322 The asparagine-linked sugar chains were released as oligosaccharides from purified CD45 by hydrazinolysis. 8251489 2 62 theme asparagine-linked 240:256 arg1 chains 264:269 The asparagine-linked sugar chains 236:269 The asparagine-linked sugar chains 236:269 The asparagine-linked sugar chains were released as oligosaccharides from purified CD45 by hydrazinolysis. 8251489 6 63 gly sialylated 732:741 arg1 oligosaccharides 743:758 the sialylated oligosaccharides 728:758 the sialylated oligosaccharides 728:758 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 4 64 theme sugar 418:422 arg1 chains 424:429 These sugar chains 412:429 These sugar chains 412:429 These sugar chains were converted to radioactive oligosaccharides by reduction with NaB3H4 and separated into neutral and acidic fractions by paper electrophoresis. 8251489 0 65 theme common 56:61 arg1 CD45 71:74 human leukocyte common antigen CD45 40:74 human leukocyte common antigen CD45 40:74 Structural study of the sugar chains of human leukocyte common antigen CD45. 8251489 9 66 theme N-acetyllactosamine 1346:1364 arg1 groups 1367:1372 the poly(N-acetyllactosamine) groups 1337:1372 the poly(N-acetyllactosamine) groups 1337:1372 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 6 67 contain have 852:855 arg1 oligosaccharides 835:850 the oligosaccharides 831:850 the oligosaccharides 831:850 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 6 67 contain have 852:855 arg2 residues 891:898 only alpha-2,6-linked sialic acid residues 857:898 only alpha-2,6-linked sialic acid residues 857:898 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 0 68 theme CD45 71:74 arg1 chains 30:35 the sugar chains 20:35 the sugar chains of human leukocyte common antigen CD45 20:74 Structural study of the sugar chains of human leukocyte common antigen CD45. 8251489 7 69 theme column 1040:1045 arg1 chromatography 1047:1060 Bio-Gel P-4 column chromatography 1028:1060 Bio-Gel P-4 column chromatography 1028:1060 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 8251489 1 70 theme tyrosine 135:142 arg1 CD45 117:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 1 70 theme tyrosine 135:142 arg1 phosphatase 144:154 a protein tyrosine phosphatase 125:154 a protein tyrosine phosphatase 125:154 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 10 71 theme complex-type 1535:1546 arg1 chains 1554:1559 the bi- and 2,4-branched triantennary complex-type sugar chains 1497:1559 the bi- and 2,4-branched triantennary complex-type sugar chains 1497:1559 A portion of the bi- and 2,4-branched triantennary complex-type sugar chains were bisected. 8251489 11 72 theme sugar 1597:1601 arg1 chains 1603:1608 these sugar chains 1591:1608 these sugar chains 1591:1608 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 7 73 theme Bio-Gel 1028:1034 arg1 chromatography 1047:1060 Bio-Gel P-4 column chromatography 1028:1060 Bio-Gel P-4 column chromatography 1028:1060 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 8251489 10 74 theme 2,4-branched 1509:1520 arg1 triantennary 1522:1533 2,4-branched triantennary 1509:1533 2,4-branched triantennary 1509:1533 A portion of the bi- and 2,4-branched triantennary complex-type sugar chains were bisected. 8251489 8 75 theme endoglycosidase 1129:1143 arg1 digestion 1145:1153 endoglycosidase digestion 1129:1153 endoglycosidase digestion 1129:1153 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 9 76 theme 2,4-branched 1389:1400 arg1 chains 1434:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 7 77 theme column 994:999 arg1 chromatography 1001:1014 serial lectin column chromatography 980:1014 serial lectin column chromatography followed by Bio-Gel P-4 column chromatography 980:1060 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 8251489 10 78 theme chains 1554:1559 arg1 portion 1486:1492 A portion 1484:1492 A portion of the bi- and 2,4-branched triantennary complex-type sugar chains 1484:1559 A portion of the bi- and 2,4-branched triantennary complex-type sugar chains were bisected. 8251489 9 79 theme complex-type 1415:1426 arg1 chains 1434:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 8 80 theme methylation 1162:1172 arg1 analysis 1174:1181 methylation analysis 1162:1181 methylation analysis 1162:1181 Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. 8251489 7 81 theme serial 980:985 arg1 chromatography 1001:1014 serial lectin column chromatography 980:1014 serial lectin column chromatography followed by Bio-Gel P-4 column chromatography 980:1060 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 8251489 1 82 theme leukocyte 81:89 arg1 CD45 117:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 77:120 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 1 82 theme leukocyte 81:89 arg1 phosphatase 144:154 a protein tyrosine phosphatase 125:154 a protein tyrosine phosphatase 125:154 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 3 83 theme chains 372:377 arg1 mol 359:361 Approximately 6 mol 343:361 Approximately 6 mol of sugar chains 343:377 Approximately 6 mol of sugar chains was released from 1 mol of CD45. 8251489 0 84 theme chains 30:35 arg1 study 11:15 Structural study 0:15 Structural study of the sugar chains of human leukocyte common antigen CD45. 0:75 Structural study of the sugar chains of human leukocyte common antigen CD45. 8251489 9 85 theme chains 1434:1439 arg1 chains 1434:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 the 2,4-branched triantennary complex-type sugar chains 1385:1439 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 9 85 theme chains 1434:1439 arg1 % 1380:1380 18% 1378:1380 18% of the 2,4-branched triantennary complex-type sugar chains 1378:1439 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 4 86 theme neutral 522:528 arg1 fractions 541:549 neutral and acidic fractions 522:549 neutral and acidic fractions 522:549 These sugar chains were converted to radioactive oligosaccharides by reduction with NaB3H4 and separated into neutral and acidic fractions by paper electrophoresis. 8251489 0 87 theme human 40:44 arg1 CD45 71:74 human leukocyte common antigen CD45 40:74 human leukocyte common antigen CD45 40:74 Structural study of the sugar chains of human leukocyte common antigen CD45. 8251489 6 88 theme sialic 879:884 arg1 residues 891:898 only alpha-2,6-linked sialic acid residues 857:898 only alpha-2,6-linked sialic acid residues 857:898 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 4 89 theme acidic 534:539 arg1 fractions 541:549 neutral and acidic fractions 522:549 neutral and acidic fractions 522:549 These sugar chains were converted to radioactive oligosaccharides by reduction with NaB3H4 and separated into neutral and acidic fractions by paper electrophoresis. 8251489 11 90 theme chains 1669:1674 arg1 chains 1669:1674 hybrid-type sugar chains 1651:1674 hybrid-type sugar chains 1651:1674 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 11 90 theme chains 1669:1674 arg1 amount 1619:1624 a small amount 1611:1624 a small amount of high mannose-type and hybrid-type sugar chains 1611:1674 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 11 90 theme chains 1669:1674 arg1 mannose-type 1634:1645 high mannose-type 1629:1645 high mannose-type 1629:1645 In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected. 8251489 9 91 theme N-acetyllactosamine 1457:1475 arg1 group 1477:1481 the fucosyl N-acetyllactosamine group 1445:1481 the fucosyl N-acetyllactosamine group 1445:1481 About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. 8251489 6 92 theme only 857:860 arg1 residues 891:898 only alpha-2,6-linked sialic acid residues 857:898 only alpha-2,6-linked sialic acid residues 857:898 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 6 93 theme oligosaccharides 743:758 arg1 analysis 808:815 methylation analysis 796:815 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis 717:815 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 6 93 theme oligosaccharides 743:758 arg1 Binding 717:723 Binding 717:723 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis 717:815 Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. 8251489 7 94 theme acidic 935:940 arg1 oligosaccharides 942:957 The neutral and sialidase-treated acidic oligosaccharides 901:957 The neutral and sialidase-treated acidic oligosaccharides 901:957 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 8251489 1 95 theme T 211:211 arg1 receptor 226:233 the T cell antigen receptor 207:233 the T cell antigen receptor 207:233 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 8251489 1 96 theme antigen 218:224 arg1 receptor 226:233 the T cell antigen receptor 207:233 the T cell antigen receptor 207:233 The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. 1637829 9 0 theme preparation 1585:1595 arg1 analysis 1560:1567 Compositional analysis 1546:1567 Compositional analysis of an unlabeled preparation of the protein 1546:1610 Compositional analysis of an unlabeled preparation of the protein suggested the presence of approximately 1.4 oligosaccharide units per molecule. 1637829 3 1 theme 2,6-branched 716:727 arg1 triantennary 729:740 2,6-branched triantennary 716:740 2,6-branched triantennary (13%) 716:746 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 3 1 theme 2,6-branched 716:727 arg1 % 745:745 13% 743:745 13% 743:745 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 8 2 theme high 1390:1393 arg1 structures 1408:1417 the high mannose type structures 1386:1417 the high mannose type structures 1386:1417 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 6 3 theme % 1173:1173 arg1 structures 1187:1196 4% hybrid-type structures 1172:1196 4% hybrid-type structures 1172:1196 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 4 4 theme type 843:846 arg1 structures 848:857 all complex type structures 831:857 all complex type structures 831:857 The majority of all complex type structures are core-fucosylated. 1637829 7 5 theme mannose 1348:1354 arg1 residues 1356:1363 5, 6, or 7 mannose residues 1337:1363 5, 6, or 7 mannose residues 1337:1363 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 6 6 theme acid 1236:1239 arg1 residue 1241:1247 a terminal sialic acid residue 1218:1247 a terminal sialic acid residue 1218:1247 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 1 7 theme hamster 203:209 arg1 cells 217:221 Chinese hamster ovary cells 195:221 Chinese hamster ovary cells transfected with a human prorenin cDNA 195:260 Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. 1637829 6 8 theme Recombinant 1142:1152 arg1 prorenin 1154:1161 Recombinant prorenin 1142:1161 Recombinant prorenin 1142:1161 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 3 9 theme triantennary 762:773 arg1 form 687:690 the form 683:690 the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures 683:812 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 1 10 theme cells 217:221 arg1 medium 185:190 the culture medium 173:190 the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA 173:260 Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. 1637829 9 11 theme oligosaccharide 1656:1670 arg1 units 1672:1676 approximately 1.4 oligosaccharide units 1638:1676 approximately 1.4 oligosaccharide units 1638:1676 Compositional analysis of an unlabeled preparation of the protein suggested the presence of approximately 1.4 oligosaccharide units per molecule. 1637829 6 12 theme sialic 1229:1234 arg1 residue 1241:1247 a terminal sialic acid residue 1218:1247 a terminal sialic acid residue 1218:1247 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 3 13 theme complex 666:672 arg1 % 620:620 Approximately 61% 604:620 Approximately 61% of the oligosaccharides on the molecule 604:660 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 3 13 theme complex 666:672 arg1 oligosaccharides 629:644 the oligosaccharides 625:644 the oligosaccharides on the molecule 625:660 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 3 13 theme complex 666:672 arg1 type 674:677 complex type 666:677 complex type 666:677 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 0 14 from prorenin 72:79 arg1 Characterization 0:15 Characterization 0:15 Characterization of the oligosaccharide structures on recombinant human prorenin 0:79 Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. 1637829 3 15 theme triantennary 729:740 arg1 form 687:690 the form 683:690 the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures 683:812 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 8 16 theme type 1403:1406 arg1 structures 1408:1417 the high mannose type structures 1386:1417 the high mannose type structures 1386:1417 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 2 17 theme N-linked 267:274 arg1 structures 292:301 The N-linked oligosaccharide structures 263:301 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein 263:354 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 18 theme specific 556:563 arg1 glycosidases 565:576 specific glycosidases 556:576 specific glycosidases 556:576 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 19 dep in 310:311 arg1 vivo 313:316 vivo 313:316 vivo 313:316 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 5 20 theme acid 1127:1130 arg1 residues 1132:1139 more than three sialic acid residues 1104:1139 more than three sialic acid residues 1104:1139 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 2 21 with treatment 541:549 arg1 glycosidases 565:576 specific glycosidases 556:576 specific glycosidases 556:576 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 21 with treatment 541:549 arg1 analysis 594:601 methylation analysis 582:601 methylation analysis 582:601 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 1 22 theme culture 177:183 arg1 medium 185:190 the culture medium 173:190 the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA 173:260 Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. 1637829 0 23 from Characterization 0:15 arg1 prorenin 72:79 recombinant human prorenin 54:79 recombinant human prorenin 54:79 Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. 1637829 3 24 from % 620:620 arg1 molecule 653:660 the molecule 649:660 the molecule 649:660 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 3 25 theme structures 803:812 arg1 form 687:690 the form 683:690 the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures 683:812 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 0 26 theme hamster 102:108 arg1 cells 116:120 Chinese hamster ovary cells 94:120 Chinese hamster ovary cells 94:120 Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. 1637829 5 27 contain contains 1095:1102 arg2 residues 1132:1139 more than three sialic acid residues 1104:1139 more than three sialic acid residues 1104:1139 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 5 27 contain contains 1095:1102 arg1 structure 1085:1093 no tetraatennary structure 1068:1093 no tetraatennary structure 1068:1093 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 8 28 theme structures 1441:1450 arg1 structures 1408:1417 the high mannose type structures 1386:1417 the high mannose type structures 1386:1417 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 8 28 theme structures 1441:1450 arg1 % 1425:1425 10% 1423:1425 10% of the hybrid structures 1423:1450 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 8 28 theme structures 1441:1450 arg1 structures 1441:1450 the hybrid structures 1430:1450 the hybrid structures 1430:1450 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 8 28 theme structures 1441:1450 arg1 % 1381:1381 Approximately 6% 1366:1381 Approximately 6% of the high mannose type structures 1366:1417 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 2 29 theme affinity 412:419 arg1 chromatography 421:434 serial lectin affinity chromatography 398:434 serial lectin affinity chromatography 398:434 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 7 30 theme mannose 1311:1317 arg1 type 1319:1322 high mannose type 1306:1322 high mannose type 1306:1322 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 7 30 theme mannose 1311:1317 arg1 % 1266:1266 The remaining 35% 1250:1266 The remaining 35% of the structures on the molecule 1250:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 7 30 theme mannose 1311:1317 arg1 structures 1275:1284 the structures 1271:1284 the structures on the molecule 1271:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 2 31 theme chromatography 487:500 arg1 treatment 541:549 treatment 541:549 treatment with specific glycosidases and methylation analysis 541:601 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 31 theme chromatography 487:500 arg1 combination 383:393 a combination 381:393 a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography 381:535 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 0 32 from structures 40:49 arg1 prorenin 72:79 recombinant human prorenin 54:79 recombinant human prorenin 54:79 Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. 1637829 2 33 theme serial 398:403 arg1 chromatography 421:434 serial lectin affinity chromatography 398:434 serial lectin affinity chromatography 398:434 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 5 34 theme terminal 928:935 arg1 galactose 937:945 terminal galactose 928:945 terminal galactose 928:945 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 3 35 from molecule 653:660 arg1 % 620:620 Approximately 61% 604:620 Approximately 61% of the oligosaccharides on the molecule 604:660 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 3 35 from molecule 653:660 arg1 oligosaccharides 629:644 the oligosaccharides 625:644 the oligosaccharides on the molecule 625:660 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 3 35 from molecule 653:660 arg1 type 674:677 complex type 666:677 complex type 666:677 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 2 36 theme liquid 451:456 arg1 chromatography 458:471 high-pressure liquid chromatography 437:471 high-pressure liquid chromatography 437:471 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 37 theme chromatography 522:535 arg1 treatment 541:549 treatment 541:549 treatment with specific glycosidases and methylation analysis 541:601 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 37 theme chromatography 522:535 arg1 combination 383:393 a combination 381:393 a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography 381:535 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 0 38 theme structures 40:49 arg1 Characterization 0:15 Characterization 0:15 Characterization of the oligosaccharide structures on recombinant human prorenin 0:79 Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. 1637829 2 39 theme size-exclusion 507:520 arg1 chromatography 522:535 size-exclusion chromatography 507:535 size-exclusion chromatography 507:535 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 5 40 theme triantennary 993:1004 arg1 structures 1006:1015 the bi- and triantennary structures 981:1015 the bi- and triantennary structures 981:1015 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 7 41 theme structures 1275:1284 arg1 type 1319:1322 high mannose type 1306:1322 high mannose type 1306:1322 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 7 41 theme structures 1275:1284 arg1 % 1266:1266 The remaining 35% 1250:1266 The remaining 35% of the structures on the molecule 1250:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 7 41 theme structures 1275:1284 arg1 structures 1275:1284 the structures 1271:1284 the structures on the molecule 1271:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 0 42 theme recombinant 54:64 arg1 prorenin 72:79 recombinant human prorenin 54:79 recombinant human prorenin 54:79 Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. 1637829 9 43 theme Compositional 1546:1558 arg1 analysis 1560:1567 Compositional analysis 1546:1567 Compositional analysis of an unlabeled preparation of the protein 1546:1610 Compositional analysis of an unlabeled preparation of the protein suggested the presence of approximately 1.4 oligosaccharide units per molecule. 1637829 2 44 theme purified 339:346 arg1 protein 348:354 the in vivo [3H]mannose-labeled, purified protein 306:354 protein 348:354 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 45 with combination 383:393 arg1 glycosidases 565:576 specific glycosidases 556:576 specific glycosidases 556:576 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 45 with combination 383:393 arg1 analysis 594:601 methylation analysis 582:601 methylation analysis 582:601 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 7 46 from molecule 1293:1300 arg1 type 1319:1322 high mannose type 1306:1322 high mannose type 1306:1322 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 7 46 from molecule 1293:1300 arg1 % 1266:1266 The remaining 35% 1250:1266 The remaining 35% of the structures on the molecule 1250:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 7 46 from molecule 1293:1300 arg1 structures 1275:1284 the structures 1271:1284 the structures on the molecule 1271:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 8 47 theme alkaline 1524:1531 arg1 phosphatase 1533:1543 alkaline phosphatase 1524:1543 alkaline phosphatase 1524:1543 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 1 48 theme prorenin 248:255 arg1 cDNA 257:260 a human prorenin cDNA 240:260 a human prorenin cDNA 240:260 Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. 1637829 5 49 theme bi- 985:987 arg1 structures 1006:1015 the bi- and triantennary structures 981:1015 the bi- and triantennary structures 981:1015 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 4 50 theme structures 848:857 arg1 core-fucosylated 863:878 core-fucosylated 863:878 core-fucosylated 863:878 The majority of all complex type structures are core-fucosylated. 1637829 4 50 theme structures 848:857 arg1 majority 819:826 The majority 815:826 The majority of all complex type structures 815:857 The majority of all complex type structures are core-fucosylated. 1637829 1 51 attach isolated 136:143 arg2 Prorenin 123:130 Prorenin 123:130 Prorenin 123:130 Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. 1637829 1 51 attach isolated 136:143 arg1 medium 185:190 the culture medium 173:190 the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA 173:260 Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. 1637829 2 52 theme in 310:311 arg1 [3H 318:320 the in vivo [3H 306:320 the in vivo [3H 306:320 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 3 53 theme oligosaccharides 629:644 arg1 % 620:620 Approximately 61% 604:620 Approximately 61% of the oligosaccharides on the molecule 604:660 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 3 53 theme oligosaccharides 629:644 arg1 oligosaccharides 629:644 the oligosaccharides 625:644 the oligosaccharides on the molecule 625:660 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 3 53 theme oligosaccharides 629:644 arg1 type 674:677 complex type 666:677 complex type 666:677 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 9 54 theme protein 1604:1610 arg1 preparation 1585:1595 an unlabeled preparation 1572:1595 an unlabeled preparation of the protein 1572:1610 Compositional analysis of an unlabeled preparation of the protein suggested the presence of approximately 1.4 oligosaccharide units per molecule. 1637829 6 55 theme hybrid-type 1175:1185 arg1 structures 1187:1196 4% hybrid-type structures 1172:1196 4% hybrid-type structures 1172:1196 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 6 56 contain contains 1163:1170 arg1 prorenin 1154:1161 Recombinant prorenin 1142:1161 Recombinant prorenin 1142:1161 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 6 56 contain contains 1163:1170 arg2 structures 1187:1196 4% hybrid-type structures 1172:1196 4% hybrid-type structures 1172:1196 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 3 57 theme 2,4-branched 749:760 arg1 triantennary 762:773 2,4-branched triantennary 749:773 2,4-branched triantennary (3%) 749:778 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 3 57 theme 2,4-branched 749:760 arg1 % 777:777 3% 776:777 3% 776:777 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 1 58 theme Chinese 195:201 arg1 cells 217:221 Chinese hamster ovary cells 195:221 Chinese hamster ovary cells transfected with a human prorenin cDNA 195:260 Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. 1637829 5 59 attach linked 898:903 arg3 position 916:923 the C-3 position 908:923 the C-3 position of terminal galactose 908:945 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 5 59 attach linked 898:903 arg2 acids 888:892 Sialic acids 881:892 Sialic acids 881:892 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 6 60 theme 4 1172:1172 arg1 % 1173:1173 % 1173:1173 % 1173:1173 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 2 61 theme mannose-labeled 322:336 arg1 protein 348:354 the in vivo [3H]mannose-labeled, purified protein 306:354 protein 348:354 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 4 62 gly core-fucosylated 863:878 arg1 core-fucosylated 863:878 core-fucosylated 863:878 core-fucosylated 863:878 The majority of all complex type structures are core-fucosylated. 1637829 4 62 gly core-fucosylated 863:878 arg1 majority 819:826 The majority 815:826 The majority of all complex type structures 815:857 The majority of all complex type structures are core-fucosylated. 1637829 4 63 theme complex 835:841 arg1 structures 848:857 all complex type structures 831:857 all complex type structures 831:857 The majority of all complex type structures are core-fucosylated. 1637829 7 64 from % 1266:1266 arg1 molecule 1293:1300 the molecule 1289:1300 the molecule 1289:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 2 65 theme [3H 318:320 arg1 protein 348:354 the in vivo [3H]mannose-labeled, purified protein 306:354 protein 348:354 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 1 66 theme ovary 211:215 arg1 cells 217:221 Chinese hamster ovary cells 195:221 Chinese hamster ovary cells transfected with a human prorenin cDNA 195:260 Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. 1637829 5 67 dep bi- 985:987 arg1 the 981:983 the 981:983 the 981:983 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 9 68 theme units 1672:1676 arg1 presence 1626:1633 the presence 1622:1633 the presence of approximately 1.4 oligosaccharide units per molecule 1622:1689 Compositional analysis of an unlabeled preparation of the protein suggested the presence of approximately 1.4 oligosaccharide units per molecule. 1637829 8 69 theme mannose 1395:1401 arg1 structures 1408:1417 the high mannose type structures 1386:1417 the high mannose type structures 1386:1417 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 6 70 theme terminal 1220:1227 arg1 residue 1241:1247 a terminal sialic acid residue 1218:1247 a terminal sialic acid residue 1218:1247 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 3 71 theme biantennary 785:795 arg1 % 800:800 43% 798:800 43% 798:800 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 3 71 theme biantennary 785:795 arg1 structures 803:812 biantennary (43%) structures 785:812 biantennary (43%) structures 785:812 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 5 72 theme tetraatennary 1071:1083 arg1 structure 1085:1093 no tetraatennary structure 1068:1093 no tetraatennary structure 1068:1093 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 8 73 theme structures 1408:1417 arg1 structures 1408:1417 the high mannose type structures 1386:1417 the high mannose type structures 1386:1417 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 8 73 theme structures 1408:1417 arg1 % 1425:1425 10% 1423:1425 10% of the hybrid structures 1423:1450 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 8 73 theme structures 1408:1417 arg1 structures 1441:1450 the hybrid structures 1430:1450 the hybrid structures 1430:1450 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 8 73 theme structures 1408:1417 arg1 % 1381:1381 Approximately 6% 1366:1381 Approximately 6% of the high mannose type structures 1366:1417 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 2 74 theme oligosaccharide 276:290 arg1 structures 292:301 The N-linked oligosaccharide structures 263:301 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein 263:354 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 5 75 theme C-3 912:914 arg1 position 916:923 the C-3 position 908:923 the C-3 position of terminal galactose 908:945 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 2 76 from structures 292:301 arg1 protein 348:354 the in vivo [3H]mannose-labeled, purified protein 306:354 protein 348:354 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 3 77 from oligosaccharides 629:644 arg1 molecule 653:660 the molecule 649:660 the molecule 649:660 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 5 78 theme Sialic 881:886 arg1 acids 888:892 Sialic acids 881:892 Sialic acids 881:892 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 8 79 with treatment 1509:1517 arg1 phosphatase 1533:1543 alkaline phosphatase 1524:1543 alkaline phosphatase 1524:1543 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 0 80 theme Chinese 94:100 arg1 cells 116:120 Chinese hamster ovary cells 94:120 Chinese hamster ovary cells 94:120 Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. 1637829 5 81 theme sialic 1120:1125 arg1 residues 1132:1139 more than three sialic acid residues 1104:1139 more than three sialic acid residues 1104:1139 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 8 82 theme hybrid 1434:1439 arg1 structures 1441:1450 the hybrid structures 1430:1450 the hybrid structures 1430:1450 Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. 1637829 0 83 theme ovary 110:114 arg1 cells 116:120 Chinese hamster ovary cells 94:120 Chinese hamster ovary cells 94:120 Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. 1637829 2 84 theme methylation 582:592 arg1 analysis 594:601 methylation analysis 582:601 methylation analysis 582:601 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 3 85 from type 674:677 arg1 form 687:690 the form 683:690 the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures 683:812 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 2 86 link N-linked 267:274 arg1 structures 292:301 The N-linked oligosaccharide structures 263:301 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein 263:354 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 7 87 theme high 1306:1309 arg1 type 1319:1322 high mannose type 1306:1322 high mannose type 1306:1322 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 7 87 theme high 1306:1309 arg1 % 1266:1266 The remaining 35% 1250:1266 The remaining 35% of the structures on the molecule 1250:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 7 87 theme high 1306:1309 arg1 structures 1275:1284 the structures 1271:1284 the structures on the molecule 1271:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 2 88 theme lectin 405:410 arg1 chromatography 421:434 serial lectin affinity chromatography 398:434 serial lectin affinity chromatography 398:434 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 89 theme ion-exchange 474:485 arg1 chromatography 487:500 ion-exchange chromatography 474:500 ion-exchange chromatography 474:500 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 6 90 contain carry 1212:1216 arg1 all 1199:1201 all 1199:1201 all 1199:1201 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 6 90 contain carry 1212:1216 arg2 residue 1241:1247 a terminal sialic acid residue 1218:1247 a terminal sialic acid residue 1218:1247 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 6 90 contain carry 1212:1216 arg1 structures 1187:1196 4% hybrid-type structures 1172:1196 4% hybrid-type structures 1172:1196 Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. 1637829 0 91 theme oligosaccharide 24:38 arg1 structures 40:49 the oligosaccharide structures 20:49 the oligosaccharide structures on recombinant human prorenin 20:79 Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. 1637829 5 92 theme galactose 937:945 arg1 position 916:923 the C-3 position 908:923 the C-3 position of terminal galactose 908:945 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 2 93 theme chromatography 458:471 arg1 treatment 541:549 treatment 541:549 treatment with specific glycosidases and methylation analysis 541:601 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 93 theme chromatography 458:471 arg1 combination 383:393 a combination 381:393 a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography 381:535 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 3 94 theme tetraantennary 695:708 arg1 form 687:690 the form 683:690 the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures 683:812 Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. 1637829 2 95 theme high-pressure 437:449 arg1 chromatography 458:471 high-pressure liquid chromatography 437:471 high-pressure liquid chromatography 437:471 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 5 96 gly sialylation 966:976 arg1 structures 1006:1015 the bi- and triantennary structures 981:1015 the bi- and triantennary structures 981:1015 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 2 97 theme chromatography 421:434 arg1 treatment 541:549 treatment 541:549 treatment with specific glycosidases and methylation analysis 541:601 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 2 97 theme chromatography 421:434 arg1 combination 383:393 a combination 381:393 a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography 381:535 The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. 1637829 0 98 theme human 66:70 arg1 prorenin 72:79 recombinant human prorenin 54:79 recombinant human prorenin 54:79 Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. 1637829 5 99 theme structures 1006:1015 arg1 sialylation 966:976 sialylation 966:976 sialylation of the bi- and triantennary structures 966:1015 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 7 100 from structures 1275:1284 arg1 molecule 1293:1300 the molecule 1289:1300 the molecule 1289:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 9 101 theme unlabeled 1575:1583 arg1 preparation 1585:1595 an unlabeled preparation 1572:1595 an unlabeled preparation of the protein 1572:1610 Compositional analysis of an unlabeled preparation of the protein suggested the presence of approximately 1.4 oligosaccharide units per molecule. 1637829 5 102 theme sialylation 966:976 arg1 degree 956:961 the degree 952:961 the degree of sialylation of the bi- and triantennary structures 952:1015 Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. 1637829 7 103 theme remaining 1254:1262 arg1 type 1319:1322 high mannose type 1306:1322 high mannose type 1306:1322 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 7 103 theme remaining 1254:1262 arg1 % 1266:1266 The remaining 35% 1250:1266 The remaining 35% of the structures on the molecule 1250:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 7 103 theme remaining 1254:1262 arg1 structures 1275:1284 the structures 1271:1284 the structures on the molecule 1271:1300 The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. 1637829 1 104 theme human 242:246 arg1 cDNA 257:260 a human prorenin cDNA 240:260 a human prorenin cDNA 240:260 Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. 7881178 6 0 theme bovine 1000:1005 arg1 rhodopsin 1007:1015 bovine rhodopsin 1000:1015 bovine rhodopsin 1000:1015 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 5 1 theme oligosaccharide 660:674 arg1 digestion 748:756 sequential exoglycosidase digestion 722:756 sequential exoglycosidase digestion in combination with methylation analysis 722:797 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 5 1 theme oligosaccharide 660:674 arg1 studies 644:650 Structural studies 633:650 Structural studies of each oligosaccharide by lectin affinity column chromatography 633:715 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 3 2 with reduction 440:448 arg1 NaB3H4 455:460 NaB3H4 455:460 NaB3H4 455:460 The sugar moieties, quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis, were converted to radioactive oligosaccharides by reduction with NaB3H4 after N-acetylation. 7881178 2 3 link N-linked 239:246 arg1 chains 254:259 their N-linked sugar chains 233:259 their N-linked sugar chains 233:259 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 5 4 with combination 761:771 arg1 analysis 790:797 methylation analysis 778:797 methylation analysis 778:797 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 7 5 theme sugar 1182:1186 arg1 chains 1188:1193 the sugar chains 1178:1193 the sugar chains of rhodopsin 1178:1206 These results suggest that species-specific processing of the sugar chains of rhodopsin occurs. 7881178 2 6 dep isolation 150:158 arg1 the 146:148 the 146:148 the 146:148 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 1 7 contain containing 102:111 arg2 chains 132:137 two N-linked sugar chains 113:137 two N-linked sugar chains 113:137 Human rhodopsin is a glycoprotein containing two N-linked sugar chains. 7881178 1 7 contain containing 102:111 arg1 rhodopsin 74:82 Human rhodopsin 68:82 Human rhodopsin 68:82 Human rhodopsin is a glycoprotein containing two N-linked sugar chains. 7881178 1 7 contain containing 102:111 arg1 glycoprotein 89:100 a glycoprotein 87:100 a glycoprotein containing two N-linked sugar chains 87:137 Human rhodopsin is a glycoprotein containing two N-linked sugar chains. 7881178 5 8 theme lectin 679:684 arg1 chromatography 702:715 lectin affinity column chromatography 679:715 lectin affinity column chromatography 679:715 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 4 9 gly sialylated 609:618 arg1 derivatives 620:630 sialylated derivatives 609:630 sialylated derivatives 609:630 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 6 10 theme rhodopsin 1007:1015 arg1 chains 990:995 the sugar chains 980:995 the sugar chains of bovine rhodopsin 980:1015 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 4 11 theme high-voltage 499:510 arg1 electrophoresis 518:532 high-voltage paper electrophoresis 499:532 high-voltage paper electrophoresis 499:532 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 5 12 theme affinity 686:693 arg1 chromatography 702:715 lectin affinity column chromatography 679:715 lectin affinity column chromatography 679:715 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 7 13 theme rhodopsin 1198:1206 arg1 chains 1188:1193 the sugar chains 1178:1193 the sugar chains of rhodopsin 1178:1206 These results suggest that species-specific processing of the sugar chains of rhodopsin occurs. 7881178 6 14 theme human 1018:1022 arg1 rhodopsin 1024:1032 human rhodopsin 1018:1032 human rhodopsin 1018:1032 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 2 15 from retinas 202:208 arg1 purification 164:175 purification 164:175 purification 164:175 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 2 15 from retinas 202:208 arg1 isolation 150:158 isolation 150:158 isolation 150:158 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 6 16 theme rhodopsin 940:948 arg1 species 912:918 the major oligosaccharide species 886:918 the major oligosaccharide species of bovine and human rhodopsin 886:948 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 16 theme rhodopsin 940:948 arg1 identical 954:962 identical 954:962 identical 954:962 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 5 17 theme Structural 633:642 arg1 studies 644:650 Structural studies 633:650 Structural studies of each oligosaccharide by lectin affinity column chromatography 633:715 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 3 18 theme polypeptide 350:360 arg1 backbone 362:369 the polypeptide backbone 346:369 the polypeptide backbone 346:369 The sugar moieties, quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis, were converted to radioactive oligosaccharides by reduction with NaB3H4 after N-acetylation. 7881178 6 19 theme human 934:938 arg1 rhodopsin 940:948 bovine and human rhodopsin 923:948 bovine and human rhodopsin 923:948 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 5 20 from digestion 748:756 arg1 combination 761:771 combination 761:771 combination with methylation analysis 761:797 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 1 21 theme Human 68:72 arg1 rhodopsin 74:82 Human rhodopsin 68:82 Human rhodopsin 68:82 Human rhodopsin is a glycoprotein containing two N-linked sugar chains. 7881178 1 21 theme Human 68:72 arg1 glycoprotein 89:100 a glycoprotein 87:100 a glycoprotein containing two N-linked sugar chains 87:137 Human rhodopsin is a glycoprotein containing two N-linked sugar chains. 7881178 1 22 gly glycoprotein 89:100 arg1 rhodopsin 74:82 Human rhodopsin 68:82 Human rhodopsin 68:82 Human rhodopsin is a glycoprotein containing two N-linked sugar chains. 7881178 1 22 gly glycoprotein 89:100 arg1 glycoprotein 89:100 a glycoprotein 87:100 a glycoprotein containing two N-linked sugar chains 87:137 Human rhodopsin is a glycoprotein containing two N-linked sugar chains. 7881178 4 23 theme paper 512:516 arg1 electrophoresis 518:532 high-voltage paper electrophoresis 499:532 high-voltage paper electrophoresis 499:532 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 3 24 theme radioactive 408:418 arg1 oligosaccharides 420:435 radioactive oligosaccharides 408:435 radioactive oligosaccharides 408:435 The sugar moieties, quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis, were converted to radioactive oligosaccharides by reduction with NaB3H4 after N-acetylation. 7881178 6 25 theme isomer 1112:1117 arg1 isomers 1059:1065 sialylated isomers 1048:1065 sialylated isomers 1048:1065 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 25 theme isomer 1112:1117 arg1 concentration 1078:1090 a high concentration 1071:1090 a high concentration of a galactosylated isomer 1071:1117 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 0 26 theme Structural 0:9 arg1 studies 11:17 Structural studies 0:17 Structural studies of the N-linked sugar chains of human rhodopsin 0:65 Structural studies of the N-linked sugar chains of human rhodopsin. 7881178 6 27 theme galactosylated 1097:1110 arg1 isomer 1112:1117 a galactosylated isomer 1095:1117 a galactosylated isomer 1095:1117 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 5 28 theme sugar 866:870 arg1 chains 872:877 hybrid-type sugar chains 854:877 hybrid-type sugar chains 854:877 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 5 29 theme hybrid-type 854:864 arg1 chains 872:877 hybrid-type sugar chains 854:877 hybrid-type sugar chains 854:877 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 5 30 theme sequential 722:731 arg1 digestion 748:756 sequential exoglycosidase digestion 722:756 sequential exoglycosidase digestion in combination with methylation analysis 722:797 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 0 31 link N-linked 26:33 arg1 chains 41:46 the N-linked sugar chains 22:46 the N-linked sugar chains of human rhodopsin 22:65 Structural studies of the N-linked sugar chains of human rhodopsin. 7881178 7 32 theme species-specific 1147:1162 arg1 processing 1164:1173 species-specific processing 1147:1173 species-specific processing of the sugar chains of rhodopsin 1147:1206 These results suggest that species-specific processing of the sugar chains of rhodopsin occurs. 7881178 4 33 theme sialic 574:579 arg1 acid 581:584 sialic acid 574:584 sialic acid 574:584 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 5 34 theme exoglycosidase 733:746 arg1 digestion 748:756 sequential exoglycosidase digestion 722:756 sequential exoglycosidase digestion in combination with methylation analysis 722:797 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 6 35 theme bovine 923:928 arg1 rhodopsin 940:948 bovine and human rhodopsin 923:948 bovine and human rhodopsin 923:948 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 36 contain contains 1039:1046 arg2 isomers 1059:1065 sialylated isomers 1048:1065 sialylated isomers 1048:1065 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 36 contain contains 1039:1046 arg1 rhodopsin 1024:1032 human rhodopsin 1018:1032 human rhodopsin 1018:1032 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 36 contain contains 1039:1046 arg2 concentration 1078:1090 a high concentration 1071:1090 a high concentration of a galactosylated isomer 1071:1117 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 0 37 theme sugar 35:39 arg1 chains 41:46 the N-linked sugar chains 22:46 the N-linked sugar chains of human rhodopsin 22:65 Structural studies of the N-linked sugar chains of human rhodopsin. 7881178 5 38 from studies 644:650 arg1 combination 761:771 combination 761:771 combination with methylation analysis 761:797 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 6 39 from identical 954:962 arg1 chains 990:995 the sugar chains 980:995 the sugar chains of bovine rhodopsin 980:1015 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 0 40 theme N-linked 26:33 arg1 chains 41:46 the N-linked sugar chains 22:46 the N-linked sugar chains of human rhodopsin 22:65 Structural studies of the N-linked sugar chains of human rhodopsin. 7881178 4 41 theme acid 581:584 arg1 free 566:569 free 566:569 free 566:569 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 3 42 from backbone 362:369 arg1 oligosaccharides 324:339 oligosaccharides 324:339 oligosaccharides from the polypeptide backbone 324:369 The sugar moieties, quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis, were converted to radioactive oligosaccharides by reduction with NaB3H4 after N-acetylation. 7881178 5 43 theme column 695:700 arg1 chromatography 702:715 lectin affinity column chromatography 679:715 lectin affinity column chromatography 679:715 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 7881178 7 44 theme chains 1188:1193 arg1 processing 1164:1173 species-specific processing 1147:1173 species-specific processing of the sugar chains of rhodopsin 1147:1206 These results suggest that species-specific processing of the sugar chains of rhodopsin occurs. 7881178 6 45 theme sugar 984:988 arg1 chains 990:995 the sugar chains 980:995 the sugar chains of bovine rhodopsin 980:1015 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 1 46 link N-linked 117:124 arg1 chains 132:137 two N-linked sugar chains 113:137 two N-linked sugar chains 113:137 Human rhodopsin is a glycoprotein containing two N-linked sugar chains. 7881178 6 47 theme oligosaccharide 896:910 arg1 species 912:918 the major oligosaccharide species 886:918 the major oligosaccharide species of bovine and human rhodopsin 886:948 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 47 theme oligosaccharide 896:910 arg1 identical 954:962 identical 954:962 identical 954:962 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 2 48 theme structural 211:220 arg1 studies 222:228 structural studies 211:228 structural studies of their N-linked sugar chains 211:259 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 6 49 from chains 990:995 arg1 species 912:918 the major oligosaccharide species 886:918 the major oligosaccharide species of bovine and human rhodopsin 886:948 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 49 from chains 990:995 arg1 identical 954:962 identical 954:962 identical 954:962 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 0 50 theme chains 41:46 arg1 studies 11:17 Structural studies 0:17 Structural studies of the N-linked sugar chains of human rhodopsin 0:65 Structural studies of the N-linked sugar chains of human rhodopsin. 7881178 4 51 theme chains 554:559 arg1 chains 554:559 the sugar chains 544:559 the sugar chains 544:559 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 4 51 theme chains 554:559 arg1 % 539:539 > 96% 535:539 > 96% of the sugar chains 535:559 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 6 52 theme major 890:894 arg1 species 912:918 the major oligosaccharide species 886:918 the major oligosaccharide species of bovine and human rhodopsin 886:948 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 52 theme major 890:894 arg1 identical 954:962 identical 954:962 identical 954:962 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 53 theme high 1073:1076 arg1 concentration 1078:1090 a high concentration 1071:1090 a high concentration of a galactosylated isomer 1071:1117 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 54 dep chains 990:995 arg1 contrast 968:975 contrast 968:975 contrast 968:975 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 4 55 theme sugar 548:552 arg1 chains 554:559 the sugar chains 544:559 the sugar chains 544:559 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 3 56 theme sugar 281:285 arg1 moieties 287:294 The sugar moieties 277:294 The sugar moieties 277:294 The sugar moieties, quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis, were converted to radioactive oligosaccharides by reduction with NaB3H4 after N-acetylation. 7881178 2 57 theme human 196:200 arg1 retinas 202:208 human retinas 196:208 human retinas 196:208 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 2 58 theme chains 254:259 arg1 studies 222:228 structural studies 211:228 structural studies of their N-linked sugar chains 211:259 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 1 59 theme N-linked 117:124 arg1 chains 132:137 two N-linked sugar chains 113:137 two N-linked sugar chains 113:137 Human rhodopsin is a glycoprotein containing two N-linked sugar chains. 7881178 4 60 theme sialylated 609:618 arg1 derivatives 620:630 sialylated derivatives 609:630 sialylated derivatives 609:630 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 2 61 theme sugar 248:252 arg1 chains 254:259 their N-linked sugar chains 233:259 their N-linked sugar chains 233:259 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 1 62 theme sugar 126:130 arg1 chains 132:137 two N-linked sugar chains 113:137 two N-linked sugar chains 113:137 Human rhodopsin is a glycoprotein containing two N-linked sugar chains. 7881178 0 63 theme rhodopsin 57:65 arg1 chains 41:46 the N-linked sugar chains 22:46 the N-linked sugar chains of human rhodopsin 22:65 Structural studies of the N-linked sugar chains of human rhodopsin. 7881178 2 64 theme rhodopsins 180:189 arg1 purification 164:175 purification 164:175 purification 164:175 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 2 64 theme rhodopsins 180:189 arg1 isolation 150:158 isolation 150:158 isolation 150:158 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 2 65 theme N-linked 239:246 arg1 chains 254:259 their N-linked sugar chains 233:259 their N-linked sugar chains 233:259 After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. 7881178 0 66 theme human 51:55 arg1 rhodopsin 57:65 human rhodopsin 51:65 human rhodopsin 51:65 Structural studies of the N-linked sugar chains of human rhodopsin. 7881178 4 67 theme > 535:535 arg1 chains 554:559 the sugar chains 544:559 the sugar chains 544:559 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 4 67 theme > 535:535 arg1 % 539:539 > 96% 535:539 > 96% of the sugar chains 535:559 As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. 7881178 6 68 theme sialylated 1048:1057 arg1 isomers 1059:1065 sialylated isomers 1048:1065 sialylated isomers 1048:1065 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 6 69 gly sialylated 1048:1057 arg1 isomers 1059:1065 sialylated isomers 1048:1065 sialylated isomers 1048:1065 While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. 7881178 5 70 theme methylation 778:788 arg1 analysis 790:797 methylation analysis 778:797 methylation analysis 778:797 Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. 1555586 6 0 from placenta 1087:1094 arg1 receptor 1073:1080 human transferrin receptor 1055:1080 human transferrin receptor from placenta 1055:1094 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 7 1 theme Distinct 1322:1329 arg1 differences 1331:1341 Distinct differences 1322:1341 Distinct differences 1322:1341 Distinct differences were noted in the glycosylation pattern of the receptor from different individuals. 1555586 2 2 theme anion-exchange 417:430 arg1 chromatography 456:469 anion-exchange high-performance liquid chromatography 417:469 anion-exchange high-performance liquid chromatography 417:469 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 4 3 theme transferrin 716:726 arg1 receptor 728:735 placental transferrin receptor 706:735 placental transferrin receptor 706:735 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 3 4 theme liquid 651:656 arg1 spectrometry 677:688 liquid secondary-ion mass spectrometry 651:688 liquid secondary-ion mass spectrometry 651:688 Glycans from placental transferrin receptor were further characterized, after desialylation, by methylation analysis and, in part, by liquid secondary-ion mass spectrometry. 1555586 6 5 theme human 1055:1059 arg1 receptor 1073:1080 human transferrin receptor 1055:1080 human transferrin receptor from placenta 1055:1094 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 10 6 contain contained 1949:1957 arg2 amounts 1966:1972 larger amounts 1959:1972 larger amounts of oligomannosidic glycans with six to nine mannose residues 1959:2033 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 10 6 contain contained 1949:1957 arg2 glycans 1993:1999 oligomannosidic glycans 1977:1999 oligomannosidic glycans with six to nine mannose residues 1977:2033 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 10 6 contain contained 1949:1957 arg1 receptor 1922:1929 the receptor 1918:1929 the receptor from Hep G2 cells 1918:1947 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 2 7 link Asparagine-linked 179:195 arg1 oligosaccharides 197:212 Asparagine-linked oligosaccharides 179:212 Asparagine-linked oligosaccharides 179:212 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 8 8 theme donor 1453:1457 arg1 A 1459:1459 donor A 1453:1459 donor A 1453:1459 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 2 9 theme peptide-N4- 310:320 arg1 amidase 360:366 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase 310:366 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase 310:366 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 9 10 theme Placental 1680:1688 arg1 receptor 1702:1709 Placental transferrin receptor 1680:1709 Placental transferrin receptor from donor B 1680:1722 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 10 11 theme placental 1886:1894 arg1 receptor 1908:1915 placental transferrin receptor 1886:1915 placental transferrin receptor 1886:1915 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 2 12 theme F. 368:369 arg1 alditols 387:394 F. Oligosaccharide alditols 368:394 F. Oligosaccharide alditols 368:394 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 4 13 theme affinity 760:767 arg1 blotting 769:776 lectin affinity blotting 753:776 lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin 753:840 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 5 14 from differences 887:897 arg1 N-glycosylation 902:916 N-glycosylation 902:916 N-glycosylation of the receptor 902:932 In order to trace possible inter-individual differences in N-glycosylation of the receptor, two preparations of placental transferrin receptor purified from two donors were compared. 1555586 3 15 theme mass 672:675 arg1 spectrometry 677:688 liquid secondary-ion mass spectrometry 651:688 liquid secondary-ion mass spectrometry 651:688 Glycans from placental transferrin receptor were further characterized, after desialylation, by methylation analysis and, in part, by liquid secondary-ion mass spectrometry. 1555586 9 16 theme donor 1716:1720 arg1 B 1722:1722 donor B 1716:1722 donor B 1716:1722 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 6 17 theme N-acetyllactosaminic 1147:1166 arg1 glycans 1168:1174 diantennary and triantennary N-acetyllactosaminic glycans 1118:1174 glycans 1168:1174 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 2 18 dep glycopeptides 252:264 arg1 fractionated 401:412 fractionated 401:412 were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography 396:514 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 2 19 gly glycopeptides 252:264 arg2 glycopeptides 252:264 tryptic glycopeptides 244:264 tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography 244:514 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 2 20 theme tryptic 244:250 arg1 glycopeptides 252:264 tryptic glycopeptides 244:264 tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography 244:514 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 5 21 theme receptor 977:984 arg1 preparations 939:950 two preparations 935:950 two preparations of placental transferrin receptor purified from two donors 935:1009 In order to trace possible inter-individual differences in N-glycosylation of the receptor, two preparations of placental transferrin receptor purified from two donors were compared. 1555586 1 22 attach isolated 109:116 arg2 receptor 96:103 Human transferrin receptor 78:103 Human transferrin receptor 78:103 Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. 1555586 1 22 attach isolated 109:116 arg1 placenta 123:130 placenta 123:130 placenta 123:130 Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. 1555586 1 22 attach isolated 109:116 arg1 line 166:169 hepatocarcinoma cell line 145:169 the hepatocarcinoma cell line Hep G2 141:176 Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. 1555586 9 23 theme triantennary 1746:1757 arg1 glycans 1780:1786 triantennary N-acetyllactosaminic glycans 1746:1786 triantennary N-acetyllactosaminic glycans without fucose 1746:1801 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 4 24 theme amurensis 821:829 arg1 agglutinin 831:840 Maackia amurensis agglutinin 813:840 Maackia amurensis agglutinin 813:840 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 0 25 theme transferrin 56:66 arg1 receptor 68:75 the human transferrin receptor 46:75 the human transferrin receptor 46:75 Structure of the N-linked oligosaccharides of the human transferrin receptor. 1555586 1 26 theme hepatocarcinoma 145:159 arg1 line 166:169 hepatocarcinoma cell line 145:169 the hepatocarcinoma cell line Hep G2 141:176 Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. 1555586 5 27 theme receptor 925:932 arg1 N-glycosylation 902:916 N-glycosylation 902:916 N-glycosylation of the receptor 902:932 In order to trace possible inter-individual differences in N-glycosylation of the receptor, two preparations of placental transferrin receptor purified from two donors were compared. 1555586 8 28 dep amounts 1621:1627 arg1 addition 1603:1610 addition 1603:1610 addition 1603:1610 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 29 theme N-acetylglucosamine 1571:1589 arg1 residue 1591:1597 the innermost N-acetylglucosamine residue 1557:1597 the innermost N-acetylglucosamine residue 1557:1597 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 7 30 theme different 1404:1412 arg1 individuals 1414:1424 different individuals 1404:1424 different individuals 1404:1424 Distinct differences were noted in the glycosylation pattern of the receptor from different individuals. 1555586 2 31 theme N-acetyl-beta-glucosaminyl 322:347 arg1 amidase 360:366 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase 310:366 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase 310:366 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 2 32 theme anion-exchange 486:499 arg1 chromatography 501:514 high-pH anion-exchange chromatography 478:514 high-pH anion-exchange chromatography 478:514 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 7 33 theme receptor 1390:1397 arg1 pattern 1375:1381 the glycosylation pattern 1357:1381 the glycosylation pattern of the receptor from different individuals 1357:1424 Distinct differences were noted in the glycosylation pattern of the receptor from different individuals. 1555586 1 34 theme Human 78:82 arg1 receptor 96:103 Human transferrin receptor 78:103 Human transferrin receptor 78:103 Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. 1555586 10 35 from receptor 1908:1915 arg1 Distinct 1872:1879 Distinct 1872:1879 Distinct 1872:1879 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 3 36 theme placental 530:538 arg1 receptor 552:559 placental transferrin receptor 530:559 placental transferrin receptor 530:559 Glycans from placental transferrin receptor were further characterized, after desialylation, by methylation analysis and, in part, by liquid secondary-ion mass spectrometry. 1555586 5 37 theme transferrin 965:975 arg1 receptor 977:984 placental transferrin receptor 955:984 placental transferrin receptor purified from two donors 955:1009 In order to trace possible inter-individual differences in N-glycosylation of the receptor, two preparations of placental transferrin receptor purified from two donors were compared. 1555586 9 38 theme mannose 1854:1860 arg1 residues 1862:1869 four or five mannose residues 1841:1869 four or five mannose residues 1841:1869 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 10 39 theme Hep 1936:1938 arg1 cells 1943:1947 Hep G2 cells 1936:1947 Hep G2 cells 1936:1947 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 8 40 theme small 1615:1619 arg1 bisected 1632:1639 bisected 1632:1639 bisected 1632:1639 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 40 theme small 1615:1619 arg1 amounts 1621:1627 small amounts 1615:1627 small amounts of bisected and of incomplete diantennary species 1615:1677 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 40 theme small 1615:1619 arg1 species 1671:1677 incomplete diantennary species 1648:1677 incomplete diantennary species 1648:1677 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 7 41 theme glycosylation 1361:1373 arg1 pattern 1375:1381 the glycosylation pattern 1357:1381 the glycosylation pattern of the receptor from different individuals 1357:1424 Distinct differences were noted in the glycosylation pattern of the receptor from different individuals. 1555586 10 42 with glycans 1993:1999 arg1 residues 2026:2033 six to nine mannose residues 2006:2033 six to nine mannose residues 2006:2033 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 10 43 theme larger 1959:1964 arg1 amounts 1966:1972 larger amounts 1959:1972 larger amounts of oligomannosidic glycans with six to nine mannose residues 1959:2033 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 10 43 theme larger 1959:1964 arg1 glycans 1993:1999 oligomannosidic glycans 1977:1999 oligomannosidic glycans with six to nine mannose residues 1977:2033 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 4 44 theme nigra 792:796 arg1 agglutinin 798:807 Sambucus nigra agglutinin 783:807 Sambucus nigra agglutinin 783:807 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 0 45 theme oligosaccharides 26:41 arg1 Structure 0:8 Structure 0:8 Structure of the N-linked oligosaccharides of the human transferrin receptor 0:75 Structure of the N-linked oligosaccharides of the human transferrin receptor. 1555586 9 46 from B 1722:1722 arg1 receptor 1702:1709 Placental transferrin receptor 1680:1709 Placental transferrin receptor from donor B 1680:1722 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 10 47 from cells 1943:1947 arg1 receptor 1922:1929 the receptor 1918:1929 the receptor from Hep G2 cells 1918:1947 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 4 48 with blotting 769:776 arg1 agglutinin 831:840 Maackia amurensis agglutinin 813:840 Maackia amurensis agglutinin 813:840 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 4 48 with blotting 769:776 arg1 agglutinin 798:807 Sambucus nigra agglutinin 783:807 Sambucus nigra agglutinin 783:807 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 6 49 contain carries 1110:1116 arg2 glycans 1168:1174 diantennary and triantennary N-acetyllactosaminic glycans 1118:1174 glycans 1168:1174 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 6 49 contain carries 1110:1116 arg2 residues 1222:1229 the galactose residues 1208:1229 the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues 1208:1319 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 6 49 contain carries 1110:1116 arg1 receptor 1073:1080 human transferrin receptor 1055:1080 human transferrin receptor from placenta 1055:1094 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 6 49 contain carries 1110:1116 arg2 species 1199:1205 hybrid-type species 1187:1205 hybrid-type species 1187:1205 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 10 50 theme glycans 1993:1999 arg1 amounts 1966:1972 larger amounts 1959:1972 larger amounts of oligomannosidic glycans with six to nine mannose residues 1959:2033 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 10 50 theme glycans 1993:1999 arg1 glycans 1993:1999 oligomannosidic glycans 1977:1999 oligomannosidic glycans with six to nine mannose residues 1977:2033 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 6 51 theme acid 1307:1310 arg1 residues 1312:1319 (alpha 2-3)-linked sialic acid residues 1281:1319 (alpha 2-3)-linked sialic acid residues 1281:1319 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 4 52 theme receptor 728:735 arg1 Sialylation 691:701 Sialylation 691:701 Sialylation of placental transferrin receptor 691:735 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 6 53 link -linked 1292:1298 arg1 residues 1312:1319 (alpha 2-3)-linked sialic acid residues 1281:1319 (alpha 2-3)-linked sialic acid residues 1281:1319 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 8 54 theme species 1671:1677 arg1 bisected 1632:1639 bisected 1632:1639 bisected 1632:1639 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 54 theme species 1671:1677 arg1 amounts 1621:1627 small amounts 1615:1627 small amounts of bisected and of incomplete diantennary species 1615:1677 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 54 theme species 1671:1677 arg1 species 1671:1677 incomplete diantennary species 1648:1677 incomplete diantennary species 1648:1677 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 6 55 theme -linked 1292:1298 arg1 residues 1312:1319 (alpha 2-3)-linked sialic acid residues 1281:1319 (alpha 2-3)-linked sialic acid residues 1281:1319 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 2 56 theme high-performance 432:447 arg1 chromatography 456:469 anion-exchange high-performance liquid chromatography 417:469 anion-exchange high-performance liquid chromatography 417:469 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 10 57 gly trisialylated 2111:2123 arg1 species 2125:2131 trisialylated species 2111:2131 trisialylated species 2111:2131 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 0 58 link N-linked 17:24 arg1 oligosaccharides 26:41 the N-linked oligosaccharides 13:41 the N-linked oligosaccharides of the human transferrin receptor 13:75 Structure of the N-linked oligosaccharides of the human transferrin receptor. 1555586 6 59 theme transferrin 1061:1071 arg1 receptor 1073:1080 human transferrin receptor 1055:1080 human transferrin receptor from placenta 1055:1094 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 4 60 theme placental 706:714 arg1 receptor 728:735 placental transferrin receptor 706:735 placental transferrin receptor 706:735 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 1 61 theme Hep 171:173 arg1 G2 175:176 Hep G2 171:176 the hepatocarcinoma cell line Hep G2 141:176 Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. 1555586 8 62 contain carried 1461:1467 arg3 part 1537:1540 part 1537:1540 part fucosylated at the innermost N-acetylglucosamine residue 1537:1597 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 62 contain carried 1461:1467 arg2 glycans 1525:1531 diantennary and triantennary complex-type glycans 1483:1531 glycans 1525:1531 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 62 contain carried 1461:1467 arg1 receptor 1439:1446 Transferrin receptor 1427:1446 Transferrin receptor from donor A 1427:1459 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 4 63 theme Sambucus 783:790 arg1 agglutinin 798:807 Sambucus nigra agglutinin 783:807 Sambucus nigra agglutinin 783:807 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 10 64 theme transferrin 1896:1906 arg1 receptor 1908:1915 placental transferrin receptor 1886:1915 placental transferrin receptor 1886:1915 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 2 65 theme Oligosaccharide 371:385 arg1 alditols 387:394 F. Oligosaccharide alditols 368:394 F. Oligosaccharide alditols 368:394 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 9 66 theme transferrin 1690:1700 arg1 receptor 1702:1709 Placental transferrin receptor 1680:1709 Placental transferrin receptor from donor B 1680:1722 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 8 67 theme bisected 1632:1639 arg1 bisected 1632:1639 bisected 1632:1639 bisected 1632:1639 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 67 theme bisected 1632:1639 arg1 amounts 1621:1627 small amounts 1615:1627 small amounts of bisected and of incomplete diantennary species 1615:1677 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 67 theme bisected 1632:1639 arg1 species 1671:1677 incomplete diantennary species 1648:1677 incomplete diantennary species 1648:1677 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 3 68 theme secondary-ion 658:670 arg1 spectrometry 677:688 liquid secondary-ion mass spectrometry 651:688 liquid secondary-ion mass spectrometry 651:688 Glycans from placental transferrin receptor were further characterized, after desialylation, by methylation analysis and, in part, by liquid secondary-ion mass spectrometry. 1555586 2 69 with glycopeptides 252:264 arg1 amidase 360:366 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase 310:366 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase 310:366 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 2 69 with glycopeptides 252:264 arg1 H 305:305 endo-beta-N-acetylglucosaminidase H 271:305 endo-beta-N-acetylglucosaminidase H 271:305 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 9 70 theme hybrid-type 1807:1817 arg1 oligosaccharides 1819:1834 hybrid-type oligosaccharides 1807:1834 hybrid-type oligosaccharides with four or five mannose residues 1807:1869 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 4 71 theme lectin 753:758 arg1 blotting 769:776 lectin affinity blotting 753:776 lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin 753:840 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 2 72 theme glycopeptides 252:264 arg1 treatment 231:239 treatment 231:239 treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography 231:514 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 6 73 theme triantennary 1134:1145 arg1 glycans 1168:1174 diantennary and triantennary N-acetyllactosaminic glycans 1118:1174 glycans 1168:1174 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 9 74 with oligosaccharides 1819:1834 arg1 residues 1862:1869 four or five mannose residues 1841:1869 four or five mannose residues 1841:1869 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 8 75 from A 1459:1459 arg1 receptor 1439:1446 Transferrin receptor 1427:1446 Transferrin receptor from donor A 1427:1459 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 76 theme Transferrin 1427:1437 arg1 receptor 1439:1446 Transferrin receptor 1427:1446 Transferrin receptor from donor A 1427:1459 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 6 77 theme diantennary 1118:1128 arg1 glycans 1168:1174 diantennary and triantennary N-acetyllactosaminic glycans 1118:1174 glycans 1168:1174 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 7 78 from individuals 1414:1424 arg1 pattern 1375:1381 the glycosylation pattern 1357:1381 the glycosylation pattern of the receptor from different individuals 1357:1424 Distinct differences were noted in the glycosylation pattern of the receptor from different individuals. 1555586 8 79 theme complex-type 1512:1523 arg1 glycans 1525:1531 diantennary and triantennary complex-type glycans 1483:1531 glycans 1525:1531 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 80 theme incomplete 1648:1657 arg1 species 1671:1677 incomplete diantennary species 1648:1677 incomplete diantennary species 1648:1677 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 9 81 theme N-acetyllactosaminic 1759:1778 arg1 glycans 1780:1786 triantennary N-acetyllactosaminic glycans 1746:1786 triantennary N-acetyllactosaminic glycans without fucose 1746:1801 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 10 82 dep nine 2013:2016 arg1 to 2010:2011 to 2010:2011 to 2010:2011 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 0 83 theme receptor 68:75 arg1 oligosaccharides 26:41 the N-linked oligosaccharides 13:41 the N-linked oligosaccharides of the human transferrin receptor 13:75 Structure of the N-linked oligosaccharides of the human transferrin receptor. 1555586 2 84 theme endo-beta-N-acetylglucosaminidase 271:303 arg1 H 305:305 endo-beta-N-acetylglucosaminidase H 271:305 endo-beta-N-acetylglucosaminidase H 271:305 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 8 85 theme diantennary 1483:1493 arg1 glycans 1525:1531 diantennary and triantennary complex-type glycans 1483:1531 glycans 1525:1531 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 6 86 theme galactose 1212:1220 arg1 species 1199:1205 hybrid-type species 1187:1205 hybrid-type species 1187:1205 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 6 86 theme galactose 1212:1220 arg1 residues 1222:1229 the galactose residues 1208:1229 the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues 1208:1319 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 4 87 theme Maackia 813:819 arg1 agglutinin 831:840 Maackia amurensis agglutinin 813:840 Maackia amurensis agglutinin 813:840 Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. 1555586 5 88 theme inter-individual 870:885 arg1 differences 887:897 possible inter-individual differences 861:897 possible inter-individual differences in N-glycosylation of the receptor 861:932 In order to trace possible inter-individual differences in N-glycosylation of the receptor, two preparations of placental transferrin receptor purified from two donors were compared. 1555586 1 89 theme cell 161:164 arg1 line 166:169 hepatocarcinoma cell line 145:169 the hepatocarcinoma cell line Hep G2 141:176 Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. 1555586 5 90 theme possible 861:868 arg1 differences 887:897 possible inter-individual differences 861:897 possible inter-individual differences in N-glycosylation of the receptor 861:932 In order to trace possible inter-individual differences in N-glycosylation of the receptor, two preparations of placental transferrin receptor purified from two donors were compared. 1555586 2 91 theme asparagine 349:358 arg1 amidase 360:366 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase 310:366 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase 310:366 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 6 92 theme hybrid-type 1187:1197 arg1 species 1199:1205 hybrid-type species 1187:1205 hybrid-type species 1187:1205 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 6 92 theme hybrid-type 1187:1197 arg1 residues 1222:1229 the galactose residues 1208:1229 the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues 1208:1319 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 8 93 theme innermost 1561:1569 arg1 residue 1591:1597 the innermost N-acetylglucosamine residue 1557:1597 the innermost N-acetylglucosamine residue 1557:1597 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 5 94 gly N-glycosylation 902:916 arg1 receptor 925:932 the receptor 921:932 the receptor 921:932 In order to trace possible inter-individual differences in N-glycosylation of the receptor, two preparations of placental transferrin receptor purified from two donors were compared. 1555586 10 95 theme oligomannosidic 1977:1991 arg1 glycans 1993:1999 oligomannosidic glycans 1977:1999 oligomannosidic glycans with six to nine mannose residues 1977:2033 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 8 96 gly fucosylated 1542:1552 arg1 part 1537:1540 part 1537:1540 part fucosylated at the innermost N-acetylglucosamine residue 1537:1597 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 8 96 gly fucosylated 1542:1552 arg2 residue 1591:1597 the innermost N-acetylglucosamine residue 1557:1597 the innermost N-acetylglucosamine residue 1557:1597 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 6 97 theme alpha 1282:1286 arg1 2-3 1288:1290 alpha 2-3 1282:1290 alpha 2-3 1282:1290 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 9 98 with glycans 1780:1786 arg1 residues 1862:1869 four or five mannose residues 1841:1869 four or five mannose residues 1841:1869 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 2 99 theme high-pH 478:484 arg1 chromatography 501:514 high-pH anion-exchange chromatography 478:514 high-pH anion-exchange chromatography 478:514 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 5 100 theme placental 955:963 arg1 receptor 977:984 placental transferrin receptor 955:984 placental transferrin receptor purified from two donors 955:1009 In order to trace possible inter-individual differences in N-glycosylation of the receptor, two preparations of placental transferrin receptor purified from two donors were compared. 1555586 1 101 theme transferrin 84:94 arg1 receptor 96:103 Human transferrin receptor 78:103 Human transferrin receptor 78:103 Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. 1555586 1 102 dep line 166:169 arg1 G2 175:176 Hep G2 171:176 the hepatocarcinoma cell line Hep G2 141:176 Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. 1555586 3 103 theme transferrin 540:550 arg1 receptor 552:559 placental transferrin receptor 530:559 placental transferrin receptor 530:559 Glycans from placental transferrin receptor were further characterized, after desialylation, by methylation analysis and, in part, by liquid secondary-ion mass spectrometry. 1555586 0 104 theme N-linked 17:24 arg1 oligosaccharides 26:41 the N-linked oligosaccharides 13:41 the N-linked oligosaccharides of the human transferrin receptor 13:75 Structure of the N-linked oligosaccharides of the human transferrin receptor. 1555586 7 105 gly glycosylation 1361:1373 arg1 receptor 1390:1397 the receptor 1386:1397 the receptor 1386:1397 Distinct differences were noted in the glycosylation pattern of the receptor from different individuals. 1555586 2 106 theme Asparagine-linked 179:195 arg1 oligosaccharides 197:212 Asparagine-linked oligosaccharides 179:212 Asparagine-linked oligosaccharides 179:212 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 1555586 10 107 theme complex-type 2055:2066 arg1 oligosaccharides 2068:2083 complex-type oligosaccharides 2055:2083 complex-type oligosaccharides apart from mono-, di- and trisialylated species 2055:2131 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 8 108 theme triantennary 1499:1510 arg1 glycans 1525:1531 diantennary and triantennary complex-type glycans 1483:1531 glycans 1525:1531 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 9 109 contain carried 1738:1744 arg2 oligosaccharides 1819:1834 hybrid-type oligosaccharides 1807:1834 hybrid-type oligosaccharides with four or five mannose residues 1807:1869 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 9 109 contain carried 1738:1744 arg1 receptor 1702:1709 Placental transferrin receptor 1680:1709 Placental transferrin receptor from donor B 1680:1722 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 9 109 contain carried 1738:1744 arg2 glycans 1780:1786 triantennary N-acetyllactosaminic glycans 1746:1786 triantennary N-acetyllactosaminic glycans without fucose 1746:1801 Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. 1555586 0 110 theme human 50:54 arg1 receptor 68:75 the human transferrin receptor 46:75 the human transferrin receptor 46:75 Structure of the N-linked oligosaccharides of the human transferrin receptor. 1555586 6 111 dep -linked 1292:1298 arg1 2-3 1288:1290 alpha 2-3 1282:1290 alpha 2-3 1282:1290 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 3 112 theme methylation 613:623 arg1 analysis 625:632 methylation analysis 613:632 methylation analysis 613:632 Glycans from placental transferrin receptor were further characterized, after desialylation, by methylation analysis and, in part, by liquid secondary-ion mass spectrometry. 1555586 10 113 gly tetrasialylated 2039:2053 arg1 oligosaccharides 2068:2083 complex-type oligosaccharides 2055:2083 complex-type oligosaccharides apart from mono-, di- and trisialylated species 2055:2131 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 10 114 theme trisialylated 2111:2123 arg1 species 2125:2131 trisialylated species 2111:2131 trisialylated species 2111:2131 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 10 115 theme mannose 2018:2024 arg1 residues 2026:2033 six to nine mannose residues 2006:2033 six to nine mannose residues 2006:2033 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 6 116 theme sialic 1300:1305 arg1 residues 1312:1319 (alpha 2-3)-linked sialic acid residues 1281:1319 (alpha 2-3)-linked sialic acid residues 1281:1319 The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. 1555586 10 117 theme G2 1940:1941 arg1 cells 1943:1947 Hep G2 cells 1936:1947 Hep G2 cells 1936:1947 Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species. 1555586 8 118 theme diantennary 1659:1669 arg1 species 1671:1677 incomplete diantennary species 1648:1677 incomplete diantennary species 1648:1677 Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. 1555586 3 119 from receptor 552:559 arg1 Glycans 517:523 Glycans 517:523 Glycans from placental transferrin receptor 517:559 Glycans from placental transferrin receptor were further characterized, after desialylation, by methylation analysis and, in part, by liquid secondary-ion mass spectrometry. 1555586 2 120 theme liquid 449:454 arg1 chromatography 456:469 anion-exchange high-performance liquid chromatography 417:469 anion-exchange high-performance liquid chromatography 417:469 Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. 6698998 5 0 from data 734:737 arg1 Leb-anti-Leb 752:763 Leb-anti-Leb 752:763 Leb-anti-Leb 752:763 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 5 0 from data 734:737 arg1 H-anti-H 742:749 H-anti-H 742:749 H-anti-H 742:749 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 5 0 from data 734:737 arg1 systems 779:785 I-anti-I systems 770:785 I-anti-I systems 770:785 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 3 1 theme neutral 476:482 arg1 fraction 500:507 the neutral oligosaccharide fraction 472:507 the neutral oligosaccharide fraction 472:507 Ten oligosaccharides (I-X), representing 80.3% of the neutral oligosaccharide fraction, have been purified to homogeneity and their structures determined. 6698998 2 2 theme borohydride 292:302 arg1 treatment 304:312 alkaline borohydride treatment 283:312 alkaline borohydride treatment 283:312 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 2 3 dep neutral 348:354 arg1 % 361:361 72.1% 357:361 72.1% 357:361 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 2 4 theme alkaline 283:290 arg1 treatment 304:312 alkaline borohydride treatment 283:312 alkaline borohydride treatment 283:312 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 5 5 theme hemagglutination 706:721 arg1 data 734:737 hemagglutination inhibition data 706:737 hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems 706:785 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 5 6 theme inhibition 723:732 arg1 data 734:737 hemagglutination inhibition data 706:737 hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems 706:785 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 5 7 dep proposed 831:838 arg1 see 903:905 see 903:905 see text 903:910 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 4 8 theme sugar 630:634 arg1 units 636:640 4 to 12 sugar units 622:640 4 to 12 sugar units 622:640 These oligosaccharides ranged in length from 4 to 12 sugar units and contained mono-, bi-, and triantennary structures. 6698998 2 9 theme heterogeneous 320:332 arg1 population 334:343 a heterogeneous population 318:343 a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols 318:406 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 0 10 theme Structural 0:9 arg1 characterization 11:26 Structural characterization 0:26 Structural characterization of neutral oligosaccharides of human H+Leb+ gastric mucin. 0:85 Structural characterization of neutral oligosaccharides of human H+Leb+ gastric mucin. 6698998 2 11 with secretors 232:240 arg1 H+Leb 259:263 blood group H+Leb 247:263 blood group H+Leb 247:263 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 2 12 theme acidic 368:373 arg1 alditols 399:406 neutral (72.1%) and acidic (27.9%) oligosaccharide alditols 348:406 neutral (72.1%) and acidic (27.9%) oligosaccharide alditols 348:406 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 0 13 theme neutral 31:37 arg1 oligosaccharides 39:54 neutral oligosaccharides 31:54 neutral oligosaccharides of human H+Leb+ gastric mucin 31:84 Structural characterization of neutral oligosaccharides of human H+Leb+ gastric mucin. 6698998 1 14 theme carbohydrate 104:115 arg1 chains 117:122 carbohydrate chains 104:122 carbohydrate chains of human gastric mucin 104:145 The structure of carbohydrate chains of human gastric mucin was investigated. 6698998 4 15 dep 12 627:628 arg1 to 624:625 to 624:625 to 624:625 These oligosaccharides ranged in length from 4 to 12 sugar units and contained mono-, bi-, and triantennary structures. 6698998 1 16 theme chains 117:122 arg1 structure 91:99 The structure 87:99 The structure of carbohydrate chains of human gastric mucin 87:145 The structure of carbohydrate chains of human gastric mucin was investigated. 6698998 2 17 theme alditols 399:406 arg1 population 334:343 a heterogeneous population 318:343 a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols 318:406 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 2 18 theme neutral 348:354 arg1 alditols 399:406 neutral (72.1%) and acidic (27.9%) oligosaccharide alditols 348:406 neutral (72.1%) and acidic (27.9%) oligosaccharide alditols 348:406 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 5 19 theme structural 807:816 arg1 analyses 818:825 structural analyses 807:825 structural analyses 807:825 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 2 20 theme blood 247:251 arg1 H+Leb 259:263 blood group H+Leb 247:263 blood group H+Leb 247:263 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 2 21 theme oligosaccharide 383:397 arg1 alditols 399:406 neutral (72.1%) and acidic (27.9%) oligosaccharide alditols 348:406 neutral (72.1%) and acidic (27.9%) oligosaccharide alditols 348:406 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 0 22 theme oligosaccharides 39:54 arg1 characterization 11:26 Structural characterization 0:26 Structural characterization of neutral oligosaccharides of human H+Leb+ gastric mucin. 0:85 Structural characterization of neutral oligosaccharides of human H+Leb+ gastric mucin. 6698998 5 23 theme analyses 818:825 arg1 results 796:802 the results 792:802 the results of structural analyses 792:825 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 5 23 theme analyses 818:825 arg1 data 734:737 hemagglutination inhibition data 706:737 hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems 706:785 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 0 24 theme H+Leb+ 65:70 arg1 mucin 80:84 human H+Leb+ gastric mucin 59:84 human H+Leb+ gastric mucin 59:84 Structural characterization of neutral oligosaccharides of human H+Leb+ gastric mucin. 6698998 5 25 theme following 844:852 arg1 structures 854:863 the following structures 840:863 the following structures for these oligosaccharides 840:890 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 5 26 theme I-anti-I 770:777 arg1 systems 779:785 I-anti-I systems 770:785 I-anti-I systems 770:785 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 2 27 theme secretors 232:240 arg1 aspirates 215:223 pronase-degraded gastric aspirates 190:223 pronase-degraded gastric aspirates of the secretors with blood group H+Leb 190:263 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 4 28 theme triantennary 672:683 arg1 structures 685:694 triantennary structures 672:694 triantennary structures 672:694 These oligosaccharides ranged in length from 4 to 12 sugar units and contained mono-, bi-, and triantennary structures. 6698998 0 29 theme human 59:63 arg1 mucin 80:84 human H+Leb+ gastric mucin 59:84 human H+Leb+ gastric mucin 59:84 Structural characterization of neutral oligosaccharides of human H+Leb+ gastric mucin. 6698998 5 30 dep see 903:905 arg1 formula 894:900 formula 894:900 formula 894:900 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 5 31 from results 796:802 arg1 Leb-anti-Leb 752:763 Leb-anti-Leb 752:763 Leb-anti-Leb 752:763 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 5 31 from results 796:802 arg1 H-anti-H 742:749 H-anti-H 742:749 H-anti-H 742:749 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 5 31 from results 796:802 arg1 systems 779:785 I-anti-I systems 770:785 I-anti-I systems 770:785 Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text) 6698998 1 32 theme human 127:131 arg1 mucin 141:145 human gastric mucin 127:145 human gastric mucin 127:145 The structure of carbohydrate chains of human gastric mucin was investigated. 6698998 4 33 contain contained 646:654 arg2 mono- 656:660 mono- 656:660 mono- 656:660 These oligosaccharides ranged in length from 4 to 12 sugar units and contained mono-, bi-, and triantennary structures. 6698998 4 33 contain contained 646:654 arg2 structures 685:694 triantennary structures 672:694 triantennary structures 672:694 These oligosaccharides ranged in length from 4 to 12 sugar units and contained mono-, bi-, and triantennary structures. 6698998 4 33 contain contained 646:654 arg1 oligosaccharides 583:598 These oligosaccharides 577:598 These oligosaccharides 577:598 These oligosaccharides ranged in length from 4 to 12 sugar units and contained mono-, bi-, and triantennary structures. 6698998 4 33 contain contained 646:654 arg2 bi- 663:665 bi- 663:665 bi- 663:665 These oligosaccharides ranged in length from 4 to 12 sugar units and contained mono-, bi-, and triantennary structures. 6698998 1 34 theme gastric 133:139 arg1 mucin 141:145 human gastric mucin 127:145 human gastric mucin 127:145 The structure of carbohydrate chains of human gastric mucin was investigated. 6698998 2 35 theme gastric 207:213 arg1 aspirates 215:223 pronase-degraded gastric aspirates 190:223 pronase-degraded gastric aspirates of the secretors with blood group H+Leb 190:263 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 2 36 dep acidic 368:373 arg1 % 380:380 27.9% 376:380 27.9% 376:380 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 1 37 theme mucin 141:145 arg1 chains 117:122 carbohydrate chains 104:122 carbohydrate chains of human gastric mucin 104:145 The structure of carbohydrate chains of human gastric mucin was investigated. 6698998 0 38 theme mucin 80:84 arg1 oligosaccharides 39:54 neutral oligosaccharides 31:54 neutral oligosaccharides of human H+Leb+ gastric mucin 31:84 Structural characterization of neutral oligosaccharides of human H+Leb+ gastric mucin. 6698998 2 39 theme pronase-degraded 190:205 arg1 aspirates 215:223 pronase-degraded gastric aspirates 190:223 pronase-degraded gastric aspirates of the secretors with blood group H+Leb 190:263 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 3 40 theme oligosaccharide 484:498 arg1 fraction 500:507 the neutral oligosaccharide fraction 472:507 the neutral oligosaccharide fraction 472:507 Ten oligosaccharides (I-X), representing 80.3% of the neutral oligosaccharide fraction, have been purified to homogeneity and their structures determined. 6698998 0 41 theme gastric 72:78 arg1 mucin 80:84 human H+Leb+ gastric mucin 59:84 human H+Leb+ gastric mucin 59:84 Structural characterization of neutral oligosaccharides of human H+Leb+ gastric mucin. 6698998 2 42 theme group 253:257 arg1 H+Leb 259:263 blood group H+Leb 247:263 blood group H+Leb 247:263 The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. 6698998 3 43 theme fraction 500:507 arg1 % 467:467 80.3% 463:467 80.3% of the neutral oligosaccharide fraction 463:507 Ten oligosaccharides (I-X), representing 80.3% of the neutral oligosaccharide fraction, have been purified to homogeneity and their structures determined. 6698998 3 43 theme fraction 500:507 arg1 fraction 500:507 the neutral oligosaccharide fraction 472:507 the neutral oligosaccharide fraction 472:507 Ten oligosaccharides (I-X), representing 80.3% of the neutral oligosaccharide fraction, have been purified to homogeneity and their structures determined. 9666724 2 0 from end 479:481 arg1 2-6Gal 433:438 2-6Gal 433:438 2-6Gal 433:438 These separation methods are complementary and allow distinction between isomeric mono- and disialylated oligosaccharides, which terminate with Sia alpha 2-6Gal or Sia alpha 2-3Gal at the nonreducing end. 9666724 3 1 theme desorption/ionization 573:593 arg1 spectrometry 615:626 matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 551:626 matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 551:626 Collected fractions of 2-AMAC-derivatized glycans were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, before and after desialylation. 9666724 3 2 theme time-of-flight 595:608 arg1 spectrometry 615:626 matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 551:626 matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 551:626 Collected fractions of 2-AMAC-derivatized glycans were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, before and after desialylation. 9666724 3 3 theme Collected 484:492 arg1 fractions 494:502 Collected fractions 484:502 Collected fractions of 2-AMAC-derivatized glycans 484:532 Collected fractions of 2-AMAC-derivatized glycans were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, before and after desialylation. 9666724 0 4 from analysis 38:45 arg1 transferrin 71:81 transferrin 71:81 transferrin 71:81 Two-dimensional chromatography in the analysis of complex glycans from transferrin. 9666724 0 5 theme Two-dimensional 0:14 arg1 chromatography 16:29 Two-dimensional chromatography 0:29 Two-dimensional chromatography 0:29 Two-dimensional chromatography in the analysis of complex glycans from transferrin. 9666724 2 6 theme mono- 361:365 arg1 oligosaccharides 384:399 isomeric mono- and disialylated oligosaccharides 352:399 isomeric mono- and disialylated oligosaccharides 352:399 These separation methods are complementary and allow distinction between isomeric mono- and disialylated oligosaccharides, which terminate with Sia alpha 2-6Gal or Sia alpha 2-3Gal at the nonreducing end. 9666724 0 7 dep chromatography 16:29 arg1 analysis 38:45 the analysis 34:45 the analysis of complex glycans from transferrin 34:81 Two-dimensional chromatography in the analysis of complex glycans from transferrin. 9666724 2 8 theme isomeric 352:359 arg1 oligosaccharides 384:399 isomeric mono- and disialylated oligosaccharides 352:399 isomeric mono- and disialylated oligosaccharides 352:399 These separation methods are complementary and allow distinction between isomeric mono- and disialylated oligosaccharides, which terminate with Sia alpha 2-6Gal or Sia alpha 2-3Gal at the nonreducing end. 9666724 2 9 theme nonreducing 467:477 arg1 end 479:481 the nonreducing end 463:481 the nonreducing end 463:481 These separation methods are complementary and allow distinction between isomeric mono- and disialylated oligosaccharides, which terminate with Sia alpha 2-6Gal or Sia alpha 2-3Gal at the nonreducing end. 9666724 1 10 theme reversed- 213:221 arg1 chromatography 263:276 either reversed- or normal-phase high-performance liquid chromatography 206:276 either reversed- or normal-phase high-performance liquid chromatography 206:276 Oligosaccharides released from human transferrin have been derivatized with 2-aminoacridone (2-AMAC) prior to analysis by either reversed- or normal-phase high-performance liquid chromatography. 9666724 0 11 from transferrin 71:81 arg1 analysis 38:45 the analysis 34:45 the analysis of complex glycans from transferrin 34:81 Two-dimensional chromatography in the analysis of complex glycans from transferrin. 9666724 0 11 from transferrin 71:81 arg1 glycans 58:64 complex glycans 50:64 complex glycans from transferrin 50:81 Two-dimensional chromatography in the analysis of complex glycans from transferrin. 9666724 1 12 theme normal-phase 226:237 arg1 chromatography 263:276 either reversed- or normal-phase high-performance liquid chromatography 206:276 either reversed- or normal-phase high-performance liquid chromatography 206:276 Oligosaccharides released from human transferrin have been derivatized with 2-aminoacridone (2-AMAC) prior to analysis by either reversed- or normal-phase high-performance liquid chromatography. 9666724 0 13 theme glycans 58:64 arg1 analysis 38:45 the analysis 34:45 the analysis of complex glycans from transferrin 34:81 Two-dimensional chromatography in the analysis of complex glycans from transferrin. 9666724 1 14 attach released 101:108 arg2 Oligosaccharides 84:99 Oligosaccharides 84:99 Oligosaccharides released from human transferrin 84:131 Oligosaccharides released from human transferrin have been derivatized with 2-aminoacridone (2-AMAC) prior to analysis by either reversed- or normal-phase high-performance liquid chromatography. 9666724 1 14 attach released 101:108 arg1 transferrin 121:131 human transferrin 115:131 human transferrin 115:131 Oligosaccharides released from human transferrin have been derivatized with 2-aminoacridone (2-AMAC) prior to analysis by either reversed- or normal-phase high-performance liquid chromatography. 9666724 3 15 theme matrix-assisted 551:565 arg1 spectrometry 615:626 matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 551:626 matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 551:626 Collected fractions of 2-AMAC-derivatized glycans were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, before and after desialylation. 9666724 0 16 theme complex 50:56 arg1 glycans 58:64 complex glycans 50:64 complex glycans from transferrin 50:81 Two-dimensional chromatography in the analysis of complex glycans from transferrin. 9666724 3 17 theme laser 567:571 arg1 spectrometry 615:626 matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 551:626 matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 551:626 Collected fractions of 2-AMAC-derivatized glycans were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, before and after desialylation. 9666724 2 18 gly disialylated 371:382 arg1 oligosaccharides 384:399 isomeric mono- and disialylated oligosaccharides 352:399 isomeric mono- and disialylated oligosaccharides 352:399 These separation methods are complementary and allow distinction between isomeric mono- and disialylated oligosaccharides, which terminate with Sia alpha 2-6Gal or Sia alpha 2-3Gal at the nonreducing end. 9666724 1 19 theme human 115:119 arg1 transferrin 121:131 human transferrin 115:131 human transferrin 115:131 Oligosaccharides released from human transferrin have been derivatized with 2-aminoacridone (2-AMAC) prior to analysis by either reversed- or normal-phase high-performance liquid chromatography. 9666724 1 20 theme high-performance 239:254 arg1 chromatography 263:276 either reversed- or normal-phase high-performance liquid chromatography 206:276 either reversed- or normal-phase high-performance liquid chromatography 206:276 Oligosaccharides released from human transferrin have been derivatized with 2-aminoacridone (2-AMAC) prior to analysis by either reversed- or normal-phase high-performance liquid chromatography. 9666724 2 21 theme disialylated 371:382 arg1 oligosaccharides 384:399 isomeric mono- and disialylated oligosaccharides 352:399 isomeric mono- and disialylated oligosaccharides 352:399 These separation methods are complementary and allow distinction between isomeric mono- and disialylated oligosaccharides, which terminate with Sia alpha 2-6Gal or Sia alpha 2-3Gal at the nonreducing end. 9666724 1 22 theme liquid 256:261 arg1 chromatography 263:276 either reversed- or normal-phase high-performance liquid chromatography 206:276 either reversed- or normal-phase high-performance liquid chromatography 206:276 Oligosaccharides released from human transferrin have been derivatized with 2-aminoacridone (2-AMAC) prior to analysis by either reversed- or normal-phase high-performance liquid chromatography. 9666724 3 23 theme 2-AMAC-derivatized 507:524 arg1 glycans 526:532 2-AMAC-derivatized glycans 507:532 2-AMAC-derivatized glycans 507:532 Collected fractions of 2-AMAC-derivatized glycans were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, before and after desialylation. 9666724 2 24 theme separation 285:294 arg1 methods 296:302 These separation methods 279:302 These separation methods 279:302 These separation methods are complementary and allow distinction between isomeric mono- and disialylated oligosaccharides, which terminate with Sia alpha 2-6Gal or Sia alpha 2-3Gal at the nonreducing end. 9666724 3 25 theme glycans 526:532 arg1 fractions 494:502 Collected fractions 484:502 Collected fractions of 2-AMAC-derivatized glycans 484:532 Collected fractions of 2-AMAC-derivatized glycans were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, before and after desialylation. 9666724 3 26 theme mass 610:613 arg1 spectrometry 615:626 matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 551:626 matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 551:626 Collected fractions of 2-AMAC-derivatized glycans were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, before and after desialylation. 1627559 0 0 theme salivary 82:89 arg1 mucins 91:96 human salivary mucins 76:96 human salivary mucins 76:96 The broad diversity of neutral and sialylated oligosaccharides derived from human salivary mucins. 1627559 4 1 theme atom 559:562 arg1 spectrometry 581:592 fast atom bombardment mass spectrometry 554:592 fast atom bombardment mass spectrometry 554:592 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 7 2 dep 31 948:949 arg1 described 976:984 described 976:984 have not been previously described in human saliva 951:1000 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 4 3 with combination 537:547 arg1 analysis 610:617 methylation analysis 598:617 methylation analysis 598:617 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 4 3 with combination 537:547 arg1 spectrometry 581:592 fast atom bombardment mass spectrometry 554:592 fast atom bombardment mass spectrometry 554:592 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 0 4 theme human 76:80 arg1 mucins 91:96 human salivary mucins 76:96 human salivary mucins 76:96 The broad diversity of neutral and sialylated oligosaccharides derived from human salivary mucins. 1627559 7 5 dep structures 1030:1039 arg1 see 1052:1054 see 1052:1054 see text 1052:1059 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 4 6 theme mass 576:579 arg1 spectrometry 581:592 fast atom bombardment mass spectrometry 554:592 fast atom bombardment mass spectrometry 554:592 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 3 7 theme gel 406:408 arg1 filtration 410:419 gel filtration 406:419 gel filtration 406:419 Neutral and monosialylated oligosaccharide-alditols were purified by ion-exchange chromatography, gel filtration, and HPLC. 1627559 1 8 with mucins 151:156 arg1 O 196:196 blood group O 184:196 blood group O 184:196 Mucin glycopeptides were prepared from the salivary mucins of 20 healthy donors with blood group O. 1627559 2 9 theme borohydride 285:295 arg1 treatment 297:305 alkaline borohydride treatment 276:305 alkaline borohydride treatment 276:305 The carbohydrate chains of the high-molecular-weight mucins were released by alkaline borohydride treatment. 1627559 3 10 theme ion-exchange 377:388 arg1 chromatography 390:403 ion-exchange chromatography 377:403 ion-exchange chromatography 377:403 Neutral and monosialylated oligosaccharide-alditols were purified by ion-exchange chromatography, gel filtration, and HPLC. 1627559 5 11 theme mucins 730:735 arg1 chains 750:755 the salivary mucins carbohydrate chains 717:755 the salivary mucins carbohydrate chains 717:755 Thirty-seven oligosaccharide-alditols were characterized and illustrate the extreme diversity of the salivary mucins carbohydrate chains. 1627559 5 12 theme salivary 721:728 arg1 chains 750:755 the salivary mucins carbohydrate chains 717:755 the salivary mucins carbohydrate chains 717:755 Thirty-seven oligosaccharide-alditols were characterized and illustrate the extreme diversity of the salivary mucins carbohydrate chains. 1627559 2 13 theme alkaline 276:283 arg1 treatment 297:305 alkaline borohydride treatment 276:305 alkaline borohydride treatment 276:305 The carbohydrate chains of the high-molecular-weight mucins were released by alkaline borohydride treatment. 1627559 7 14 dep see 1052:1054 arg1 [formula 1042:1049 [formula 1042:1049 [formula 1042:1049 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 1 15 theme healthy 164:170 arg1 donors 172:177 20 healthy donors 161:177 20 healthy donors 161:177 Mucin glycopeptides were prepared from the salivary mucins of 20 healthy donors with blood group O. 1627559 4 16 theme fast 554:557 arg1 spectrometry 581:592 fast atom bombardment mass spectrometry 554:592 fast atom bombardment mass spectrometry 554:592 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 5 17 theme carbohydrate 737:748 arg1 chains 750:755 the salivary mucins carbohydrate chains 717:755 the salivary mucins carbohydrate chains 717:755 Thirty-seven oligosaccharide-alditols were characterized and illustrate the extreme diversity of the salivary mucins carbohydrate chains. 1627559 6 18 theme oral 894:897 arg1 cavity 899:904 the oral cavity 890:904 the oral cavity 890:904 This diversity might represent a mosaic of bacterial adhesion sites and be involved in the early events of the nonimmune defense of the oral cavity. 1627559 6 19 theme sites 820:824 arg1 mosaic 791:796 a mosaic 789:796 a mosaic of bacterial adhesion sites 789:824 This diversity might represent a mosaic of bacterial adhesion sites and be involved in the early events of the nonimmune defense of the oral cavity. 1627559 1 20 theme donors 172:177 arg1 mucins 151:156 the salivary mucins 138:156 the salivary mucins of 20 healthy donors with blood group O 138:196 Mucin glycopeptides were prepared from the salivary mucins of 20 healthy donors with blood group O. 1627559 0 21 theme broad 4:8 arg1 diversity 10:18 The broad diversity 0:18 The broad diversity of neutral and sialylated oligosaccharides 0:61 The broad diversity of neutral and sialylated oligosaccharides derived from human salivary mucins. 1627559 5 22 theme chains 750:755 arg1 diversity 704:712 the extreme diversity 692:712 the extreme diversity of the salivary mucins carbohydrate chains 692:755 Thirty-seven oligosaccharide-alditols were characterized and illustrate the extreme diversity of the salivary mucins carbohydrate chains. 1627559 7 23 theme novel 1024:1028 arg1 structures 1030:1039 novel structures 1024:1039 novel structures 1024:1039 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 7 23 theme novel 1024:1028 arg1 five 1006:1009 five 1006:1009 five 1006:1009 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 7 23 theme novel 1024:1028 arg1 31 948:949 31 948:949 31 948:949 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 7 23 theme novel 1024:1028 arg1 these 1014:1018 these 1014:1018 these 1014:1018 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 6 24 theme adhesion 811:818 arg1 sites 820:824 bacterial adhesion sites 801:824 bacterial adhesion sites 801:824 This diversity might represent a mosaic of bacterial adhesion sites and be involved in the early events of the nonimmune defense of the oral cavity. 1627559 6 25 theme bacterial 801:809 arg1 sites 820:824 bacterial adhesion sites 801:824 bacterial adhesion sites 801:824 This diversity might represent a mosaic of bacterial adhesion sites and be involved in the early events of the nonimmune defense of the oral cavity. 1627559 1 26 theme blood 184:188 arg1 O 196:196 blood group O 184:196 blood group O 184:196 Mucin glycopeptides were prepared from the salivary mucins of 20 healthy donors with blood group O. 1627559 0 27 gly sialylated 35:44 arg1 oligosaccharides 46:61 neutral and sialylated oligosaccharides 23:61 neutral and sialylated oligosaccharides 23:61 The broad diversity of neutral and sialylated oligosaccharides derived from human salivary mucins. 1627559 4 28 from spectroscopy 521:532 arg1 combination 537:547 combination 537:547 combination with fast atom bombardment mass spectrometry and methylation analysis 537:617 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 5 29 theme extreme 696:702 arg1 diversity 704:712 the extreme diversity 692:712 the extreme diversity of the salivary mucins carbohydrate chains 692:755 Thirty-seven oligosaccharide-alditols were characterized and illustrate the extreme diversity of the salivary mucins carbohydrate chains. 1627559 1 30 theme Mucin 99:103 arg1 glycopeptides 105:117 Mucin glycopeptides 99:117 Mucin glycopeptides 99:117 Mucin glycopeptides were prepared from the salivary mucins of 20 healthy donors with blood group O. 1627559 1 31 theme group 190:194 arg1 O 196:196 blood group O 184:196 blood group O 184:196 Mucin glycopeptides were prepared from the salivary mucins of 20 healthy donors with blood group O. 1627559 4 32 theme high-resolution 498:512 arg1 spectroscopy 521:532 high-resolution 1H-NMR spectroscopy 498:532 high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis 498:617 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 0 33 theme neutral 23:29 arg1 oligosaccharides 46:61 neutral and sialylated oligosaccharides 23:61 neutral and sialylated oligosaccharides 23:61 The broad diversity of neutral and sialylated oligosaccharides derived from human salivary mucins. 1627559 4 34 theme methylation 598:608 arg1 analysis 610:617 methylation analysis 598:617 methylation analysis 598:617 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 5 35 theme Thirty-seven 620:631 arg1 oligosaccharide-alditols 633:656 Thirty-seven oligosaccharide-alditols 620:656 Thirty-seven oligosaccharide-alditols 620:656 Thirty-seven oligosaccharide-alditols were characterized and illustrate the extreme diversity of the salivary mucins carbohydrate chains. 1627559 0 36 theme oligosaccharides 46:61 arg1 diversity 10:18 The broad diversity 0:18 The broad diversity of neutral and sialylated oligosaccharides 0:61 The broad diversity of neutral and sialylated oligosaccharides derived from human salivary mucins. 1627559 4 37 theme 1H-NMR 514:519 arg1 spectroscopy 521:532 high-resolution 1H-NMR spectroscopy 498:532 high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis 498:617 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 1 38 gly glycopeptides 105:117 arg2 glycopeptides 105:117 Mucin glycopeptides 99:117 Mucin glycopeptides 99:117 Mucin glycopeptides were prepared from the salivary mucins of 20 healthy donors with blood group O. 1627559 0 39 theme sialylated 35:44 arg1 oligosaccharides 46:61 neutral and sialylated oligosaccharides 23:61 neutral and sialylated oligosaccharides 23:61 The broad diversity of neutral and sialylated oligosaccharides derived from human salivary mucins. 1627559 3 40 theme monosialylated 320:333 arg1 oligosaccharide-alditols 335:358 Neutral and monosialylated oligosaccharide-alditols 308:358 Neutral and monosialylated oligosaccharide-alditols 308:358 Neutral and monosialylated oligosaccharide-alditols were purified by ion-exchange chromatography, gel filtration, and HPLC. 1627559 4 41 theme oligosaccharide-alditols 454:477 arg1 structures 436:445 The structures 432:445 The structures of the oligosaccharide-alditols 432:477 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 2 42 theme carbohydrate 203:214 arg1 chains 216:221 The carbohydrate chains 199:221 The carbohydrate chains of the high-molecular-weight mucins 199:257 The carbohydrate chains of the high-molecular-weight mucins were released by alkaline borohydride treatment. 1627559 6 43 theme defense 879:885 arg1 events 855:860 the early events 845:860 the early events of the nonimmune defense of the oral cavity 845:904 This diversity might represent a mosaic of bacterial adhesion sites and be involved in the early events of the nonimmune defense of the oral cavity. 1627559 7 44 theme these 1014:1018 arg1 structures 1030:1039 novel structures 1024:1039 novel structures 1024:1039 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 7 44 theme these 1014:1018 arg1 five 1006:1009 five 1006:1009 five 1006:1009 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 7 44 theme these 1014:1018 arg1 31 948:949 31 948:949 31 948:949 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 7 44 theme these 1014:1018 arg1 these 1014:1018 these 1014:1018 these 1014:1018 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 1627559 3 45 theme Neutral 308:314 arg1 oligosaccharide-alditols 335:358 Neutral and monosialylated oligosaccharide-alditols 308:358 Neutral and monosialylated oligosaccharide-alditols 308:358 Neutral and monosialylated oligosaccharide-alditols were purified by ion-exchange chromatography, gel filtration, and HPLC. 1627559 6 46 theme nonimmune 869:877 arg1 defense 879:885 the nonimmune defense 865:885 the nonimmune defense of the oral cavity 865:904 This diversity might represent a mosaic of bacterial adhesion sites and be involved in the early events of the nonimmune defense of the oral cavity. 1627559 6 47 theme early 849:853 arg1 events 855:860 the early events 845:860 the early events of the nonimmune defense of the oral cavity 845:904 This diversity might represent a mosaic of bacterial adhesion sites and be involved in the early events of the nonimmune defense of the oral cavity. 1627559 6 48 theme cavity 899:904 arg1 defense 879:885 the nonimmune defense 865:885 the nonimmune defense of the oral cavity 865:904 This diversity might represent a mosaic of bacterial adhesion sites and be involved in the early events of the nonimmune defense of the oral cavity. 1627559 3 49 gly monosialylated 320:333 arg1 oligosaccharide-alditols 335:358 Neutral and monosialylated oligosaccharide-alditols 308:358 Neutral and monosialylated oligosaccharide-alditols 308:358 Neutral and monosialylated oligosaccharide-alditols were purified by ion-exchange chromatography, gel filtration, and HPLC. 1627559 2 50 theme mucins 252:257 arg1 chains 216:221 The carbohydrate chains 199:221 The carbohydrate chains of the high-molecular-weight mucins 199:257 The carbohydrate chains of the high-molecular-weight mucins were released by alkaline borohydride treatment. 1627559 1 51 theme salivary 142:149 arg1 mucins 151:156 the salivary mucins 138:156 the salivary mucins of 20 healthy donors with blood group O 138:196 Mucin glycopeptides were prepared from the salivary mucins of 20 healthy donors with blood group O. 1627559 4 52 theme bombardment 564:574 arg1 spectrometry 581:592 fast atom bombardment mass spectrometry 554:592 fast atom bombardment mass spectrometry 554:592 The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. 1627559 2 53 theme high-molecular-weight 230:250 arg1 mucins 252:257 the high-molecular-weight mucins 226:257 the high-molecular-weight mucins 226:257 The carbohydrate chains of the high-molecular-weight mucins were released by alkaline borohydride treatment. 1627559 7 54 theme human 989:993 arg1 saliva 995:1000 human saliva 989:1000 human saliva 989:1000 Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] 12000758 5 0 theme high 742:745 arg1 density 747:753 a high density 740:753 a high density glycosylation 740:767 Except for a general reduction in the O-glycan chain lengths and a high density glycosylation, no common structural pattern was revealed. 12000758 4 1 theme 2-aminobenzamide-labeled 641:664 arg1 glycans 666:672 2-aminobenzamide-labeled glycans 641:672 2-aminobenzamide-labeled glycans 641:672 Comparative analyses of the O-glycan profiles were performed after hydrazinolysis and normal phase chromatography of 2-aminobenzamide-labeled glycans. 12000758 6 2 theme core 882:885 arg1 expression 889:898 core 1 expression 882:898 core 1 expression 882:898 T47D fusion protein exhibits an almost complete shift from core 2 to core 1 expression with a preponderance of sialylated glycans. 12000758 9 3 theme core 1723:1726 arg1 6-N-acetylglucosaminyltransferases 1743:1776 core 2-forming beta 6-N-acetylglucosaminyltransferases 1723:1776 core 2-forming beta 6-N-acetylglucosaminyltransferases 1723:1776 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 8 4 theme cell 1212:1215 arg1 supernatants 1217:1228 cell supernatants 1212:1228 cell supernatants 1212:1228 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 9 5 theme beta 1738:1741 arg1 6-N-acetylglucosaminyltransferases 1743:1776 core 2-forming beta 6-N-acetylglucosaminyltransferases 1723:1776 core 2-forming beta 6-N-acetylglucosaminyltransferases 1723:1776 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 8 6 theme respective 1299:1308 arg1 probes 1322:1327 the respective recombinant probes 1295:1327 the respective recombinant probes 1295:1327 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 7 7 theme 2/3-linked 1149:1158 arg1 MCF-7 1168:1172 MCF-7 1168:1172 MCF-7 1168:1172 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 7 7 theme 2/3-linked 1149:1158 arg1 fucose 1160:1165 alpha 2/3-linked fucose 1143:1165 alpha 2/3-linked fucose (MCF-7) 1143:1173 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 9 8 theme biosynthetic 1504:1515 arg1 models 1517:1522 biosynthetic models 1504:1522 biosynthetic models of MUC1 O-glycosylation in breast cancer 1504:1563 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 5 9 theme O-glycan 713:720 arg1 lengths 728:734 the O-glycan chain lengths 709:734 the O-glycan chain lengths 709:734 Except for a general reduction in the O-glycan chain lengths and a high density glycosylation, no common structural pattern was revealed. 12000758 6 10 theme complete 852:859 arg1 shift 861:865 an almost complete shift 842:865 an almost complete shift from core 2 to core 1 expression 842:898 T47D fusion protein exhibits an almost complete shift from core 2 to core 1 expression with a preponderance of sialylated glycans. 12000758 8 11 theme identical 1246:1254 arg1 profiles 1272:1279 almost identical O-glycosylation profiles 1239:1279 almost identical O-glycosylation profiles 1239:1279 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 3 12 theme structural 314:323 arg1 information 325:335 structural information 314:335 structural information 314:335 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 12000758 5 13 theme common 773:778 arg1 pattern 791:797 no common structural pattern 770:797 no common structural pattern 770:797 Except for a general reduction in the O-glycan chain lengths and a high density glycosylation, no common structural pattern was revealed. 12000758 9 14 theme O-glycosylation 1532:1546 arg1 models 1517:1522 biosynthetic models 1504:1522 biosynthetic models of MUC1 O-glycosylation in breast cancer 1504:1563 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 9 15 theme competitive 1806:1816 arg1 sialyltransferase 1827:1843 competitive alpha 3- sialyltransferase 1806:1843 competitive alpha 3- sialyltransferase 1806:1843 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 7 16 link 2/3-linked 1149:1158 arg1 MCF-7 1168:1172 MCF-7 1168:1172 MCF-7 1168:1172 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 7 16 link 2/3-linked 1149:1158 arg1 fucose 1160:1165 alpha 2/3-linked fucose 1143:1165 alpha 2/3-linked fucose (MCF-7) 1143:1173 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 9 17 theme breast 1551:1556 arg1 cancer 1558:1563 breast cancer 1551:1563 breast cancer 1551:1563 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 5 18 theme density 747:753 arg1 glycosylation 755:767 a high density glycosylation 740:767 a high density glycosylation 740:767 Except for a general reduction in the O-glycan chain lengths and a high density glycosylation, no common structural pattern was revealed. 12000758 1 19 theme prevalent 137:145 arg1 glycosylation 160:172 prevalent core 2-based glycosylation 137:172 prevalent core 2-based glycosylation 137:172 High density and prevalent core 2-based glycosylation. 12000758 7 20 theme ZR75-1 979:984 arg1 cells 986:990 MCF-7, MDA-MB231, and ZR75-1 cells 957:990 MCF-7, MDA-MB231, and ZR75-1 cells 957:990 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 9 21 theme short 1651:1655 arg1 glycans 1681:1687 short sialylated core 1-based glycans 1651:1687 short sialylated core 1-based glycans 1651:1687 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 7 22 theme 3-linked 1099:1106 arg1 MDA-MB231 1121:1129 MDA-MB231 1121:1129 MDA-MB231 1121:1129 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 7 22 theme 3-linked 1099:1106 arg1 acid 1115:1118 alpha 3-linked sialic acid 1093:1118 alpha 3-linked sialic acid (MDA-MB231, ZR75-1) 1093:1138 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 7 23 theme core 1048:1051 arg1 glycans 1061:1067 core 2-based glycans 1048:1067 core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7) 1048:1173 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 1 24 theme 2-based 152:158 arg1 glycosylation 160:172 prevalent core 2-based glycosylation 137:172 prevalent core 2-based glycosylation 137:172 High density and prevalent core 2-based glycosylation. 12000758 8 25 theme O-glycan 1390:1397 arg1 profiles 1399:1406 the authentic O-glycan profiles 1376:1406 the authentic O-glycan profiles of the cells 1376:1419 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 0 26 theme breast 99:104 arg1 mucin 113:117 endogenous breast cancer mucin 88:117 endogenous breast cancer mucin 88:117 Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. 12000758 7 27 theme repeat 1013:1018 arg1 peptide 1020:1026 the MUC1 repeat peptide 1004:1026 the MUC1 repeat peptide 1004:1026 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 4 28 theme O-glycan 552:559 arg1 profiles 561:568 the O-glycan profiles 548:568 the O-glycan profiles 548:568 Comparative analyses of the O-glycan profiles were performed after hydrazinolysis and normal phase chromatography of 2-aminobenzamide-labeled glycans. 12000758 8 29 theme cells 1415:1419 arg1 profiles 1399:1406 the authentic O-glycan profiles 1376:1406 the authentic O-glycan profiles of the cells 1376:1419 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 0 30 theme mucin 113:117 arg1 profiles 76:83 cell-specific O-glycosylation profiles 46:83 cell-specific O-glycosylation profiles of endogenous breast cancer mucin 46:117 Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. 12000758 9 31 from patterns 1437:1444 arg1 majority 1453:1460 the majority 1449:1460 the majority of cells under study 1449:1481 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 9 32 theme core 1608:1611 arg1 structures 1637:1646 normal core 2-based polylactosamine structures 1601:1646 normal core 2-based polylactosamine structures 1601:1646 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 3 33 theme endogenous 384:393 arg1 mucin 395:399 endogenous mucin 384:399 endogenous mucin 384:399 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 12000758 2 34 link O-linked 195:202 arg1 chains 211:216 the O-linked glycan chains 191:216 the O-linked glycan chains of tumor-associated MUC1 191:241 Knowledge about the O-linked glycan chains of tumor-associated MUC1 is primarily based on enzymatic and immunochemical evidence. 12000758 9 35 theme polylactosamine 1621:1635 arg1 structures 1637:1646 normal core 2-based polylactosamine structures 1601:1646 normal core 2-based polylactosamine structures 1601:1646 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 6 36 from core 872:875 arg1 shift 861:865 an almost complete shift 842:865 an almost complete shift from core 2 to core 1 expression 842:898 T47D fusion protein exhibits an almost complete shift from core 2 to core 1 expression with a preponderance of sialylated glycans. 12000758 3 37 theme recombinant 417:427 arg1 probe 443:447 a recombinant glycosylation probe 415:447 a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines 415:521 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 12000758 4 38 theme Comparative 524:534 arg1 analyses 536:543 Comparative analyses 524:543 Comparative analyses of the O-glycan profiles 524:568 Comparative analyses of the O-glycan profiles were performed after hydrazinolysis and normal phase chromatography of 2-aminobenzamide-labeled glycans. 12000758 3 39 theme MUC1 470:473 arg1 repeats 482:488 six MUC1 tandem repeats 466:488 six MUC1 tandem repeats in four breast cancer cell lines 466:521 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 12000758 0 40 theme Recombinant 0:10 arg1 authentically 23:35 Recombinant MUC1 probe authentically 0:35 Recombinant MUC1 probe authentically 0:35 Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. 12000758 3 41 theme cancer 505:510 arg1 lines 517:521 four breast cancer cell lines 493:521 four breast cancer cell lines 493:521 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 12000758 0 42 theme probe 17:21 arg1 authentically 23:35 Recombinant MUC1 probe authentically 0:35 Recombinant MUC1 probe authentically 0:35 Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. 12000758 5 43 from reduction 696:704 arg1 lengths 728:734 the O-glycan chain lengths 709:734 the O-glycan chain lengths 709:734 Except for a general reduction in the O-glycan chain lengths and a high density glycosylation, no common structural pattern was revealed. 12000758 6 44 theme glycans 935:941 arg1 preponderance 907:919 a preponderance 905:919 a preponderance of sialylated glycans 905:941 T47D fusion protein exhibits an almost complete shift from core 2 to core 1 expression with a preponderance of sialylated glycans. 12000758 9 45 theme sialylated 1657:1666 arg1 glycans 1681:1687 short sialylated core 1-based glycans 1651:1687 short sialylated core 1-based glycans 1651:1687 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 4 46 theme phase 617:621 arg1 chromatography 623:636 normal phase chromatography 610:636 normal phase chromatography 610:636 Comparative analyses of the O-glycan profiles were performed after hydrazinolysis and normal phase chromatography of 2-aminobenzamide-labeled glycans. 12000758 2 47 theme glycan 204:209 arg1 chains 211:216 the O-linked glycan chains 191:216 the O-linked glycan chains of tumor-associated MUC1 191:241 Knowledge about the O-linked glycan chains of tumor-associated MUC1 is primarily based on enzymatic and immunochemical evidence. 12000758 9 48 theme structural 1426:1435 arg1 patterns 1437:1444 The structural patterns 1422:1444 The structural patterns in the majority of cells under study 1422:1481 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 9 49 theme 1-based 1673:1679 arg1 glycans 1681:1687 short sialylated core 1-based glycans 1651:1687 short sialylated core 1-based glycans 1651:1687 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 9 50 with conflict 1490:1497 arg1 models 1517:1522 biosynthetic models 1504:1522 biosynthetic models of MUC1 O-glycosylation in breast cancer 1504:1563 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 0 51 theme O-glycosylation 60:74 arg1 profiles 76:83 cell-specific O-glycosylation profiles 46:83 cell-specific O-glycosylation profiles of endogenous breast cancer mucin 46:117 Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. 12000758 2 52 theme MUC1 238:241 arg1 chains 211:216 the O-linked glycan chains 191:216 the O-linked glycan chains of tumor-associated MUC1 191:241 Knowledge about the O-linked glycan chains of tumor-associated MUC1 is primarily based on enzymatic and immunochemical evidence. 12000758 6 53 theme fusion 818:823 arg1 protein 825:831 T47D fusion protein 813:831 T47D fusion protein 813:831 T47D fusion protein exhibits an almost complete shift from core 2 to core 1 expression with a preponderance of sialylated glycans. 12000758 5 54 from glycosylation 755:767 arg1 lengths 728:734 the O-glycan chain lengths 709:734 the O-glycan chain lengths 709:734 Except for a general reduction in the O-glycan chain lengths and a high density glycosylation, no common structural pattern was revealed. 12000758 9 55 from models 1517:1522 arg1 cancer 1558:1563 breast cancer 1551:1563 breast cancer 1551:1563 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 9 56 theme cells 1465:1469 arg1 majority 1453:1460 the majority 1449:1460 the majority of cells under study 1449:1481 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 9 57 theme reduced 1703:1709 arg1 activity 1711:1718 the reduced activity 1699:1718 the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases 1699:1776 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 5 58 theme chain 722:726 arg1 lengths 728:734 the O-glycan chain lengths 709:734 the O-glycan chain lengths 709:734 Except for a general reduction in the O-glycan chain lengths and a high density glycosylation, no common structural pattern was revealed. 12000758 9 59 theme 2-forming 1728:1736 arg1 6-N-acetylglucosaminyltransferases 1743:1776 core 2-forming beta 6-N-acetylglucosaminyltransferases 1723:1776 core 2-forming beta 6-N-acetylglucosaminyltransferases 1723:1776 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 4 60 theme glycans 666:672 arg1 hydrazinolysis 591:604 hydrazinolysis 591:604 hydrazinolysis 591:604 Comparative analyses of the O-glycan profiles were performed after hydrazinolysis and normal phase chromatography of 2-aminobenzamide-labeled glycans. 12000758 4 60 theme glycans 666:672 arg1 chromatography 623:636 normal phase chromatography 610:636 normal phase chromatography 610:636 Comparative analyses of the O-glycan profiles were performed after hydrazinolysis and normal phase chromatography of 2-aminobenzamide-labeled glycans. 12000758 7 61 theme alpha 1143:1147 arg1 MCF-7 1168:1172 MCF-7 1168:1172 MCF-7 1168:1172 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 7 61 theme alpha 1143:1147 arg1 fucose 1160:1165 alpha 2/3-linked fucose 1143:1165 alpha 2/3-linked fucose (MCF-7) 1143:1173 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 9 62 theme 6-N-acetylglucosaminyltransferases 1743:1776 arg1 activity 1711:1718 the reduced activity 1699:1718 the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases 1699:1776 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 9 63 from cancer 1558:1563 arg1 models 1517:1522 biosynthetic models 1504:1522 biosynthetic models of MUC1 O-glycosylation in breast cancer 1504:1563 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 8 64 theme recombinant 1310:1320 arg1 probes 1322:1327 the respective recombinant probes 1295:1327 the respective recombinant probes 1295:1327 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 9 65 theme MUC1 1527:1530 arg1 O-glycosylation 1532:1546 MUC1 O-glycosylation 1527:1546 MUC1 O-glycosylation in breast cancer 1527:1563 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 5 66 theme structural 780:789 arg1 pattern 791:797 no common structural pattern 770:797 no common structural pattern 770:797 Except for a general reduction in the O-glycan chain lengths and a high density glycosylation, no common structural pattern was revealed. 12000758 2 67 theme enzymatic 265:273 arg1 evidence 294:301 enzymatic and immunochemical evidence 265:301 enzymatic and immunochemical evidence 265:301 Knowledge about the O-linked glycan chains of tumor-associated MUC1 is primarily based on enzymatic and immunochemical evidence. 12000758 8 68 theme O-glycosylation 1256:1270 arg1 profiles 1272:1279 almost identical O-glycosylation profiles 1239:1279 almost identical O-glycosylation profiles 1239:1279 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 9 69 theme alpha 1818:1822 arg1 sialyltransferase 1827:1843 competitive alpha 3- sialyltransferase 1806:1843 competitive alpha 3- sialyltransferase 1806:1843 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 7 70 theme sialic 1108:1113 arg1 MDA-MB231 1121:1129 MDA-MB231 1121:1129 MDA-MB231 1121:1129 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 7 70 theme sialic 1108:1113 arg1 acid 1115:1118 alpha 3-linked sialic acid 1093:1118 alpha 3-linked sialic acid (MDA-MB231, ZR75-1) 1093:1138 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 9 71 theme sialyltransferase 1827:1843 arg1 overexpression 1788:1801 overexpression 1788:1801 overexpression of competitive alpha 3- sialyltransferase 1788:1843 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 9 72 gly O-glycosylation 1532:1546 arg1 cancer 1558:1563 breast cancer 1551:1563 breast cancer 1551:1563 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 8 73 theme fusion 1350:1355 arg1 proteins 1357:1364 the fusion proteins 1346:1364 the fusion proteins 1346:1364 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 7 74 theme alpha 1093:1097 arg1 MDA-MB231 1121:1129 MDA-MB231 1121:1129 MDA-MB231 1121:1129 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 7 74 theme alpha 1093:1097 arg1 acid 1115:1118 alpha 3-linked sialic acid 1093:1118 alpha 3-linked sialic acid (MDA-MB231, ZR75-1) 1093:1138 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 1 75 theme core 147:150 arg1 glycosylation 160:172 prevalent core 2-based glycosylation 137:172 prevalent core 2-based glycosylation 137:172 High density and prevalent core 2-based glycosylation. 12000758 0 76 theme endogenous 88:97 arg1 mucin 113:117 endogenous breast cancer mucin 88:117 endogenous breast cancer mucin 88:117 Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. 12000758 2 77 theme immunochemical 279:292 arg1 evidence 294:301 enzymatic and immunochemical evidence 265:301 enzymatic and immunochemical evidence 265:301 Knowledge about the O-linked glycan chains of tumor-associated MUC1 is primarily based on enzymatic and immunochemical evidence. 12000758 7 78 theme 2-based 1053:1059 arg1 glycans 1061:1067 core 2-based glycans 1048:1067 core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7) 1048:1173 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 8 79 theme authentic 1380:1388 arg1 profiles 1399:1406 the authentic O-glycan profiles 1376:1406 the authentic O-glycan profiles of the cells 1376:1419 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 0 80 theme cancer 106:111 arg1 mucin 113:117 endogenous breast cancer mucin 88:117 endogenous breast cancer mucin 88:117 Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. 12000758 4 81 theme profiles 561:568 arg1 analyses 536:543 Comparative analyses 524:543 Comparative analyses of the O-glycan profiles 524:568 Comparative analyses of the O-glycan profiles were performed after hydrazinolysis and normal phase chromatography of 2-aminobenzamide-labeled glycans. 12000758 5 82 gly glycosylation 755:767 arg1 lengths 728:734 the O-glycan chain lengths 709:734 the O-glycan chain lengths 709:734 Except for a general reduction in the O-glycan chain lengths and a high density glycosylation, no common structural pattern was revealed. 12000758 9 83 theme normal 1601:1606 arg1 structures 1637:1646 normal core 2-based polylactosamine structures 1601:1646 normal core 2-based polylactosamine structures 1601:1646 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 8 84 dep T47D 1197:1200 arg1 supernatants 1217:1228 cell supernatants 1212:1228 cell supernatants 1212:1228 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 5 85 theme general 688:694 arg1 reduction 696:704 a general reduction 686:704 a general reduction in the O-glycan chain lengths 686:734 Except for a general reduction in the O-glycan chain lengths and a high density glycosylation, no common structural pattern was revealed. 12000758 9 86 theme 2-based 1613:1619 arg1 structures 1637:1646 normal core 2-based polylactosamine structures 1601:1646 normal core 2-based polylactosamine structures 1601:1646 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 3 87 theme mucin 395:399 arg1 scarcity 372:379 the scarcity 368:379 the scarcity of endogenous mucin 368:399 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 12000758 0 88 theme MUC1 12:15 arg1 authentically 23:35 Recombinant MUC1 probe authentically 0:35 Recombinant MUC1 probe authentically 0:35 Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. 12000758 9 89 theme structures 1637:1646 arg1 truncation 1587:1596 the truncation 1583:1596 the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans 1583:1687 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 9 89 theme structures 1637:1646 arg1 due 1692:1694 due 1692:1694 due 1692:1694 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 3 90 theme glycosylation 429:441 arg1 probe 443:447 a recombinant glycosylation probe 415:447 a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines 415:521 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 12000758 4 91 theme normal 610:615 arg1 chromatography 623:636 normal phase chromatography 610:636 normal phase chromatography 610:636 Comparative analyses of the O-glycan profiles were performed after hydrazinolysis and normal phase chromatography of 2-aminobenzamide-labeled glycans. 12000758 6 92 gly sialylated 924:933 arg1 glycans 935:941 sialylated glycans 924:941 sialylated glycans 924:941 T47D fusion protein exhibits an almost complete shift from core 2 to core 1 expression with a preponderance of sialylated glycans. 12000758 3 93 theme tandem 475:480 arg1 repeats 482:488 six MUC1 tandem repeats 466:488 six MUC1 tandem repeats in four breast cancer cell lines 466:521 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 12000758 7 94 theme MUC1 1008:1011 arg1 peptide 1020:1026 the MUC1 repeat peptide 1004:1026 the MUC1 repeat peptide 1004:1026 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 1 95 theme High 120:123 arg1 density 125:131 High density 120:131 High density 120:131 High density and prevalent core 2-based glycosylation. 12000758 3 96 theme cell 512:515 arg1 lines 517:521 four breast cancer cell lines 493:521 four breast cancer cell lines 493:521 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 12000758 0 97 theme cell-specific 46:58 arg1 profiles 76:83 cell-specific O-glycosylation profiles 46:83 cell-specific O-glycosylation profiles of endogenous breast cancer mucin 46:117 Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. 12000758 6 98 theme sialylated 924:933 arg1 glycans 935:941 sialylated glycans 924:941 sialylated glycans 924:941 T47D fusion protein exhibits an almost complete shift from core 2 to core 1 expression with a preponderance of sialylated glycans. 12000758 9 99 theme core 1668:1671 arg1 glycans 1681:1687 short sialylated core 1-based glycans 1651:1687 short sialylated core 1-based glycans 1651:1687 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 2 100 theme O-linked 195:202 arg1 chains 211:216 the O-linked glycan chains 191:216 the O-linked glycan chains of tumor-associated MUC1 191:241 Knowledge about the O-linked glycan chains of tumor-associated MUC1 is primarily based on enzymatic and immunochemical evidence. 12000758 3 101 theme breast 498:503 arg1 lines 517:521 four breast cancer cell lines 493:521 four breast cancer cell lines 493:521 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 12000758 9 102 gly sialylated 1657:1666 arg1 glycans 1681:1687 short sialylated core 1-based glycans 1651:1687 short sialylated core 1-based glycans 1651:1687 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 7 103 link 3-linked 1099:1106 arg1 MDA-MB231 1121:1129 MDA-MB231 1121:1129 MDA-MB231 1121:1129 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 7 103 link 3-linked 1099:1106 arg1 acid 1115:1118 alpha 3-linked sialic acid 1093:1118 alpha 3-linked sialic acid (MDA-MB231, ZR75-1) 1093:1138 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 7 104 theme MDA-MB231 964:972 arg1 cells 986:990 MCF-7, MDA-MB231, and ZR75-1 cells 957:990 MCF-7, MDA-MB231, and ZR75-1 cells 957:990 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 8 105 from MCF-7 1206:1210 arg1 MUC1 1187:1190 Endogenous MUC1 1176:1190 Endogenous MUC1 from T47D and MCF-7 cell supernatants 1176:1228 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 9 106 from O-glycosylation 1532:1546 arg1 cancer 1558:1563 breast cancer 1551:1563 breast cancer 1551:1563 The structural patterns in the majority of cells under study are in conflict with biosynthetic models of MUC1 O-glycosylation in breast cancer, which claim that the truncation of normal core 2-based polylactosamine structures to short sialylated core 1-based glycans is due to the reduced activity of core 2-forming beta 6-N-acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3- sialyltransferase. 12000758 7 107 gly glycosylate 992:1002 arg1 peptide 1020:1026 the MUC1 repeat peptide 1004:1026 the MUC1 repeat peptide 1004:1026 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 2 108 theme tumor-associated 221:236 arg1 MUC1 238:241 tumor-associated MUC1 221:241 tumor-associated MUC1 221:241 Knowledge about the O-linked glycan chains of tumor-associated MUC1 is primarily based on enzymatic and immunochemical evidence. 12000758 6 109 theme T47D 813:816 arg1 protein 825:831 T47D fusion protein 813:831 T47D fusion protein 813:831 T47D fusion protein exhibits an almost complete shift from core 2 to core 1 expression with a preponderance of sialylated glycans. 12000758 7 110 theme MCF-7 957:961 arg1 cells 986:990 MCF-7, MDA-MB231, and ZR75-1 cells 957:990 MCF-7, MDA-MB231, and ZR75-1 cells 957:990 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 8 111 theme Endogenous 1176:1185 arg1 MUC1 1187:1190 Endogenous MUC1 1176:1190 Endogenous MUC1 from T47D and MCF-7 cell supernatants 1176:1228 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 8 112 from T47D 1197:1200 arg1 MUC1 1187:1190 Endogenous MUC1 1176:1190 Endogenous MUC1 from T47D and MCF-7 cell supernatants 1176:1228 Endogenous MUC1 from T47D and MCF-7 cell supernatants revealed almost identical O-glycosylation profiles compared with the respective recombinant probes, indicating that the fusion proteins reflected the authentic O-glycan profiles of the cells. 12000758 0 113 gly O-glycosylation 60:74 arg1 mucin 113:117 endogenous breast cancer mucin 88:117 endogenous breast cancer mucin 88:117 Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. 12000758 7 114 dep MDA-MB231 1121:1129 arg1 ZR75-1 1132:1137 ZR75-1 1132:1137 ZR75-1 1132:1137 By contrast, MCF-7, MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA-MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). 12000758 3 115 from repeats 482:488 arg1 lines 517:521 four breast cancer cell lines 493:521 four breast cancer cell lines 493:521 To obtain structural information and to overcome limitations by the scarcity of endogenous mucin, we expressed a recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four breast cancer cell lines. 3345749 6 0 dep 2 1202:1202 arg1 11a 1220:1222 11a 1220:1222 11a 1220:1222 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 0 dep 2 1202:1202 arg1 15a 1225:1227 15a 1225:1227 15a 1225:1227 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 0 dep 2 1202:1202 arg1 16c 1242:1244 16c 1242:1244 16c 1242:1244 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 0 dep 2 1202:1202 arg1 14 1213:1214 14 1213:1214 14 1213:1214 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 0 dep 2 1202:1202 arg1 7 1217:1217 7 1217:1217 7 1217:1217 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 0 dep 2 1202:1202 arg1 16a 1230:1232 16a 1230:1232 16a 1230:1232 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 0 dep 2 1202:1202 arg1 3 1205:1205 3 1205:1205 3 1205:1205 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 0 dep 2 1202:1202 arg1 12 1235:1236 12 1235:1236 12 1235:1236 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 0 dep 2 1202:1202 arg1 10a 1208:1210 10a 1208:1210 10a 1208:1210 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 4 1 theme 1H-NMR 859:864 arg1 spectroscopy 866:877 500-MHz 1H-NMR spectroscopy 851:877 500-MHz 1H-NMR spectroscopy 851:877 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 0 2 theme quantitative 196:207 arg1 analysis 215:222 quantitative sugar analysis 196:222 quantitative sugar analysis 196:222 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 3 3 theme group 458:462 arg1 patient 443:449 a patient 441:449 a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome 441:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 3 3 theme group 458:462 arg1 O 464:464 blood group O 452:464 blood group O 452:464 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 11 4 theme 1H-NMR 1772:1777 arg1 spectroscopy 1779:1790 High-resolution 1H-NMR spectroscopy 1756:1790 High-resolution 1H-NMR spectroscopy 1756:1790 High-resolution 1H-NMR spectroscopy is able to distinguish whether the Y determinant is beta(1----3) or beta(1----6) linked in such oligosaccharide-alditols. 3345749 0 5 theme analysis 215:222 arg1 combination 149:159 combination 149:159 combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis 149:222 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 0 6 attach derived 46:52 arg1 glycoproteins 77:89 respiratory-mucus glycoproteins 59:89 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 59:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 0 6 attach derived 46:52 arg2 oligosaccharides 29:44 neutral oligosaccharides 21:44 neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 21:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 3 7 from patient 443:449 arg1 chains 394:399 Carbohydrate chains 381:399 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome 381:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 3 7 from patient 443:449 arg1 glycopeptides 422:434 respiratory-mucus glycopeptides 404:434 respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome 404:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 10 8 dep beta 1743:1746 arg1 i.e. 1678:1681 i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1678:1753 i.e. 1678:1681 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 9 theme Fuc 1684:1686 arg1 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 9 theme Fuc 1684:1686 arg1 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 9 theme Fuc 1684:1686 arg1 1----3 1728:1733 1----3 1728:1733 1----3 1728:1733 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 9 theme Fuc 1684:1686 arg1 1---- 1748:1752 1---- 1748:1752 1---- 1748:1752 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 11 10 theme Y 1827:1827 arg1 beta 1844:1847 beta(1----3) 1844:1855 beta(1----3) 1844:1855 High-resolution 1H-NMR spectroscopy is able to distinguish whether the Y determinant is beta(1----3) or beta(1----6) linked in such oligosaccharide-alditols. 3345749 11 10 theme Y 1827:1827 arg1 determinant 1829:1839 the Y determinant 1823:1839 the Y determinant 1823:1839 High-resolution 1H-NMR spectroscopy is able to distinguish whether the Y determinant is beta(1----3) or beta(1----6) linked in such oligosaccharide-alditols. 3345749 4 11 theme liquid 612:617 arg1 chromatography 619:632 high-performance liquid chromatography 595:632 high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, 595:743 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 10 12 theme beta 1705:1708 arg1 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 12 theme beta 1705:1708 arg1 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 12 theme beta 1705:1708 arg1 1----3 1728:1733 1----3 1728:1733 1----3 1728:1733 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 12 theme beta 1705:1708 arg1 1---- 1748:1752 1---- 1748:1752 1---- 1748:1752 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 6 13 theme bronchial 1288:1296 arg1 mucins 1298:1303 human bronchial mucins 1282:1303 human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur 1282:1473 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 0 14 theme 500-MHz 164:170 arg1 spectroscopy 179:190 500-MHz 1H-NMR spectroscopy 164:190 500-MHz 1H-NMR spectroscopy 164:190 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 10 15 theme [Fuc 1717:1720 arg1 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 15 theme [Fuc 1717:1720 arg1 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 15 theme [Fuc 1717:1720 arg1 1----3 1728:1733 1----3 1728:1733 1----3 1728:1733 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 15 theme [Fuc 1717:1720 arg1 1---- 1748:1752 1---- 1748:1752 1---- 1748:1752 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 0 16 theme spectroscopy 179:190 arg1 combination 149:159 combination 149:159 combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis 149:222 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 6 17 with oligosaccharide-alditols 1150:1173 arg1 types 1186:1190 these types 1180:1190 these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) 1180:1245 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 9 18 theme remaining 1510:1518 arg1 compounds 1524:1532 the remaining six compounds 1506:1532 the remaining six compounds 1506:1532 Of the remaining six compounds, one is a partial structure of oligosaccharides previously described: (Formula: see text). 3345749 10 19 theme 1----4 1710:1715 arg1 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 19 theme 1----4 1710:1715 arg1 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 19 theme 1----4 1710:1715 arg1 1----3 1728:1733 1----3 1728:1733 1----3 1728:1733 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 19 theme 1----4 1710:1715 arg1 1---- 1748:1752 1---- 1748:1752 1---- 1748:1752 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 3 20 theme borohydride 557:567 arg1 treatment 569:577 alkaline borohydride treatment 548:577 alkaline borohydride treatment 548:577 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 9 21 theme compounds 1524:1532 arg1 structure 1552:1560 a partial structure 1542:1560 a partial structure of oligosaccharides previously described: (Formula: see text) 1542:1622 Of the remaining six compounds, one is a partial structure of oligosaccharides previously described: (Formula: see text). 3345749 9 21 theme compounds 1524:1532 arg1 one 1535:1537 one 1535:1537 one 1535:1537 Of the remaining six compounds, one is a partial structure of oligosaccharides previously described: (Formula: see text). 3345749 11 22 theme such 1883:1886 arg1 oligosaccharide-alditols 1888:1911 such oligosaccharide-alditols 1883:1911 such oligosaccharide-alditols 1883:1911 High-resolution 1H-NMR spectroscopy is able to distinguish whether the Y determinant is beta(1----3) or beta(1----6) linked in such oligosaccharide-alditols. 3345749 5 23 theme GalNAc 1072:1077 arg1 residue 1079:1085 the GalNAc residue 1068:1085 the GalNAc residue (core type 2 or core type 1, respectively) 1068:1128 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 0 24 theme Primary 0:6 arg1 structure 8:16 Primary structure 0:16 Primary structure 0:16 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 9 25 theme oligosaccharides 1565:1580 arg1 structure 1552:1560 a partial structure 1542:1560 a partial structure of oligosaccharides previously described: (Formula: see text) 1542:1622 Of the remaining six compounds, one is a partial structure of oligosaccharides previously described: (Formula: see text). 3345749 9 25 theme oligosaccharides 1565:1580 arg1 one 1535:1537 one 1535:1537 one 1535:1537 Of the remaining six compounds, one is a partial structure of oligosaccharides previously described: (Formula: see text). 3345749 2 26 theme beta 276:279 arg1 core 298:301 the Gal beta(1----3)GalNAc-ol core 268:301 the Gal beta(1----3)GalNAc-ol core (type 1) 268:310 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 26 theme beta 276:279 arg1 type 304:307 type 1 304:309 type 1 304:309 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 3 27 gly glycopeptides 422:434 arg2 glycopeptides 422:434 respiratory-mucus glycopeptides 404:434 respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome 404:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 3 27 gly glycopeptides 422:434 arg1 patient 443:449 a patient 441:449 a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome 441:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 3 27 gly glycopeptides 422:434 arg1 O 464:464 blood group O 452:464 blood group O 452:464 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 3 28 theme respiratory-mucus 404:420 arg1 glycopeptides 422:434 respiratory-mucus glycopeptides 404:434 respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome 404:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 6 29 theme human 1282:1286 arg1 mucins 1298:1303 human bronchial mucins 1282:1303 human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur 1282:1473 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 4 30 theme oligosaccharide-alditol 779:801 arg1 structures 803:812 35 oligosaccharide-alditol structures 776:812 35 oligosaccharide-alditol structures 776:812 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 0 31 theme oligosaccharides 29:44 arg1 structure 8:16 Primary structure 0:16 Primary structure 0:16 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 5 32 dep residue 1079:1085 arg1 type 1108:1111 core type 1 1103:1113 core type 1 1103:1113 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 5 32 dep residue 1079:1085 arg1 type 1093:1096 core type 2 1088:1098 core type 2 1088:1098 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 2 33 theme Gal 272:274 arg1 core 298:301 the Gal beta(1----3)GalNAc-ol core 268:301 the Gal beta(1----3)GalNAc-ol core (type 1) 268:310 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 33 theme Gal 272:274 arg1 type 304:307 type 1 304:309 type 1 304:309 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 4 34 theme neutral 757:763 arg1 fractions 765:773 39 neutral fractions 754:773 39 neutral fractions 754:773 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 2 35 theme Gal 319:321 arg1 beta 323:326 Gal beta 319:326 the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2) 315:378 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 35 theme Gal 319:321 arg1 beta 343:346 1----3)[GlcNAc beta(1----6) 328:354 1----3)[GlcNAc beta(1----6) 328:354 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 5 36 theme beta 988:991 arg1 GalNAc-ol 1000:1008 Gal beta(1----3)GalNAc-ol 984:1008 Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively) 984:1128 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 10 37 theme GlcNAc 1736:1741 arg1 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 37 theme GlcNAc 1736:1741 arg1 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 37 theme GlcNAc 1736:1741 arg1 1----3 1728:1733 1----3 1728:1733 1----3 1728:1733 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 37 theme GlcNAc 1736:1741 arg1 1---- 1748:1752 1---- 1748:1752 1---- 1748:1752 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 6 38 theme fibrosis 1339:1346 arg1 [Lamblin 1348:1355 cystic fibrosis [Lamblin 1332:1355 cystic fibrosis [Lamblin 1332:1355 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 38 theme fibrosis 1339:1346 arg1 J.F.G. 1457:1462 J.F.G. 1457:1462 J.F.G. 1457:1462 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 38 theme fibrosis 1339:1346 arg1 H. 1436:1437 H. 1436:1437 H. 1436:1437 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 2 39 contain having 261:266 arg2 type 372:375 type 2 372:377 type 2 372:377 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 39 contain having 261:266 arg2 core 366:369 the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core 315:369 the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2) 315:378 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 39 contain having 261:266 arg2 type 304:307 type 1 304:309 type 1 304:309 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 39 contain having 261:266 arg1 oligosaccharides 244:259 16 oligosaccharides 241:259 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2) 241:378 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 39 contain having 261:266 arg2 core 298:301 the Gal beta(1----3)GalNAc-ol core 268:301 the Gal beta(1----3)GalNAc-ol core (type 1) 268:310 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 3 40 with bronchiectasis 482:495 arg1 syndrome 517:524 a Kartagener's syndrome 502:524 a Kartagener's syndrome 502:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 10 41 dep structures 1629:1638 arg1 20 1648:1649 20 1648:1649 20 1648:1649 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 41 dep structures 1629:1638 arg1 17a 1640:1642 17a 1640:1642 17a 1640:1642 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 0 42 theme sugar 209:213 arg1 analysis 215:222 quantitative sugar analysis 196:222 quantitative sugar analysis 196:222 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 3 43 theme blood 452:456 arg1 patient 443:449 a patient 441:449 a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome 441:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 3 43 theme blood 452:456 arg1 O 464:464 blood group O 452:464 blood group O 452:464 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 4 44 theme 500-MHz 851:857 arg1 spectroscopy 866:877 500-MHz 1H-NMR spectroscopy 851:877 500-MHz 1H-NMR spectroscopy 851:877 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 9 45 dep structure 1552:1560 arg1 see 1614:1616 see 1614:1616 see text 1614:1621 Of the remaining six compounds, one is a partial structure of oligosaccharides previously described: (Formula: see text). 3345749 6 46 theme patients 1308:1315 arg1 mucins 1298:1303 human bronchial mucins 1282:1303 human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur 1282:1473 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 2 47 theme GalNAc-ol 288:296 arg1 core 298:301 the Gal beta(1----3)GalNAc-ol core 268:301 the Gal beta(1----3)GalNAc-ol core (type 1) 268:310 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 47 theme GalNAc-ol 288:296 arg1 type 304:307 type 1 304:309 type 1 304:309 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 10 48 contain contain 1651:1657 arg2 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 48 contain contain 1651:1657 arg1 structures 1629:1638 The structures 17a and 20 1625:1649 The structures 17a and 20 1625:1649 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 48 contain contain 1651:1657 arg2 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 4 49 theme chromatography 619:632 arg1 Application 580:590 Application 580:590 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, 580:743 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 10 50 theme Y 1663:1663 arg1 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 50 theme Y 1663:1663 arg1 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 6 51 theme cores 1195:1199 arg1 types 1186:1190 these types 1180:1190 these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) 1180:1245 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 5 52 contain possessing 952:961 arg2 core 965:968 a core 963:968 a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively) 963:1128 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 5 52 contain possessing 952:961 arg1 structures 940:949 16 oligosaccharide structures 921:949 16 oligosaccharide structures 921:949 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 10 53 theme alpha 1688:1692 arg1 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 53 theme alpha 1688:1692 arg1 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 53 theme alpha 1688:1692 arg1 1----3 1728:1733 1----3 1728:1733 1----3 1728:1733 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 53 theme alpha 1688:1692 arg1 1---- 1748:1752 1---- 1748:1752 1---- 1748:1752 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 4 54 theme high-performance 595:610 arg1 chromatography 619:632 high-performance liquid chromatography 595:632 high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, 595:743 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 10 55 theme Gal 1701:1703 arg1 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 55 theme Gal 1701:1703 arg1 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 55 theme Gal 1701:1703 arg1 1----3 1728:1733 1----3 1728:1733 1----3 1728:1733 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 55 theme Gal 1701:1703 arg1 1---- 1748:1752 1---- 1748:1752 1---- 1748:1752 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 0 56 theme 1H-NMR 172:177 arg1 spectroscopy 179:190 500-MHz 1H-NMR spectroscopy 164:190 500-MHz 1H-NMR spectroscopy 164:190 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 2 57 theme oligosaccharides 244:259 arg1 Structure 228:236 Structure 228:236 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 228:379 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 11 58 theme High-resolution 1756:1770 arg1 spectroscopy 1779:1790 High-resolution 1H-NMR spectroscopy 1756:1790 High-resolution 1H-NMR spectroscopy 1756:1790 High-resolution 1H-NMR spectroscopy is able to distinguish whether the Y determinant is beta(1----3) or beta(1----6) linked in such oligosaccharide-alditols. 3345749 11 59 attach linked 1873:1878 arg3 oligosaccharide-alditols 1888:1911 such oligosaccharide-alditols 1883:1911 such oligosaccharide-alditols 1883:1911 High-resolution 1H-NMR spectroscopy is able to distinguish whether the Y determinant is beta(1----3) or beta(1----6) linked in such oligosaccharide-alditols. 3345749 11 59 attach linked 1873:1878 arg2 beta 1844:1847 beta(1----3) 1844:1855 beta(1----3) 1844:1855 High-resolution 1H-NMR spectroscopy is able to distinguish whether the Y determinant is beta(1----3) or beta(1----6) linked in such oligosaccharide-alditols. 3345749 11 59 attach linked 1873:1878 arg2 determinant 1829:1839 the Y determinant 1823:1839 the Y determinant 1823:1839 High-resolution 1H-NMR spectroscopy is able to distinguish whether the Y determinant is beta(1----3) or beta(1----6) linked in such oligosaccharide-alditols. 3345749 10 60 theme 1----2 1694:1699 arg1 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 60 theme 1----2 1694:1699 arg1 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 60 theme 1----2 1694:1699 arg1 1----3 1728:1733 1----3 1728:1733 1----3 1728:1733 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 60 theme 1----2 1694:1699 arg1 1---- 1748:1752 1---- 1748:1752 1---- 1748:1752 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 5 61 theme GlcNAc 1030:1035 arg1 residue 1037:1043 a GlcNAc residue 1028:1043 a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively) 1028:1128 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 2 62 theme 1----3 281:286 arg1 core 298:301 the Gal beta(1----3)GalNAc-ol core 268:301 the Gal beta(1----3)GalNAc-ol core (type 1) 268:310 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 62 theme 1----3 281:286 arg1 type 304:307 type 1 304:309 type 1 304:309 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 4 63 theme sugar 899:903 arg1 analysis 905:912 sugar analysis 899:912 sugar analysis 899:912 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 4 64 theme aminopropyl 689:699 arg1 groups 701:706 aminopropyl groups 689:706 aminopropyl groups 689:706 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 3 65 theme alkaline 548:555 arg1 treatment 569:577 alkaline borohydride treatment 548:577 alkaline borohydride treatment 548:577 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 4 66 theme silica 657:662 arg1 other 716:720 other 716:720 other 716:720 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 4 66 theme silica 657:662 arg1 one 673:675 one 673:675 one 673:675 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 4 66 theme silica 657:662 arg1 columns 664:670 two silica columns 653:670 two silica columns 653:670 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 0 67 theme patient 96:102 arg1 glycoproteins 77:89 respiratory-mucus glycoproteins 59:89 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 59:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 5 68 theme core 1088:1091 arg1 type 1093:1096 core type 2 1088:1098 core type 2 1088:1098 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 0 69 gly glycoproteins 77:89 arg1 glycoproteins 77:89 respiratory-mucus glycoproteins 59:89 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 59:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 4 70 theme octadecyl 727:735 arg1 groups 737:742 octadecyl groups 727:742 octadecyl groups 727:742 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 10 71 theme alpha 1722:1726 arg1 beta 1743:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta 1684:1746 Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----) 1684:1753 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 71 theme alpha 1722:1726 arg1 determinant 1665:1675 the Y determinant 1659:1675 the Y determinant 1659:1675 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 71 theme alpha 1722:1726 arg1 1----3 1728:1733 1----3 1728:1733 1----3 1728:1733 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 10 71 theme alpha 1722:1726 arg1 1---- 1748:1752 1---- 1748:1752 1---- 1748:1752 The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). 3345749 9 72 dep see 1614:1616 arg1 Formula 1605:1611 Formula 1605:1611 Formula 1605:1611 Of the remaining six compounds, one is a partial structure of oligosaccharides previously described: (Formula: see text). 3345749 9 73 theme partial 1544:1550 arg1 structure 1552:1560 a partial structure 1542:1560 a partial structure of oligosaccharides previously described: (Formula: see text) 1542:1622 Of the remaining six compounds, one is a partial structure of oligosaccharides previously described: (Formula: see text). 3345749 9 73 theme partial 1544:1550 arg1 one 1535:1537 one 1535:1537 one 1535:1537 Of the remaining six compounds, one is a partial structure of oligosaccharides previously described: (Formula: see text). 3345749 3 74 theme Carbohydrate 381:392 arg1 chains 394:399 Carbohydrate chains 381:399 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome 381:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 5 75 theme oligosaccharide 924:938 arg1 structures 940:949 16 oligosaccharide structures 921:949 16 oligosaccharide structures 921:949 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 0 76 theme neutral 21:27 arg1 oligosaccharides 29:44 neutral oligosaccharides 21:44 neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 21:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 3 77 theme glycopeptides 422:434 arg1 chains 394:399 Carbohydrate chains 381:399 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome 381:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 4 78 with conjunction 882:892 arg1 analysis 905:912 sugar analysis 899:912 sugar analysis 899:912 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 3345749 5 79 attach linked 1045:1050 arg1 residue 1079:1085 the GalNAc residue 1068:1085 the GalNAc residue (core type 2 or core type 1, respectively) 1068:1128 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 5 79 attach linked 1045:1050 arg2 residue 1037:1043 a GlcNAc residue 1028:1043 a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively) 1028:1128 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 3 80 from chains 394:399 arg1 patient 443:449 a patient 441:449 a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome 441:524 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 3 80 from chains 394:399 arg1 O 464:464 blood group O 452:464 blood group O 452:464 Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. 3345749 2 81 theme GalNac-ol 356:364 arg1 core 366:369 the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core 315:369 the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2) 315:378 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 81 theme GalNac-ol 356:364 arg1 type 372:375 type 2 372:377 type 2 372:377 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 0 82 theme respiratory-mucus 59:75 arg1 glycoproteins 77:89 respiratory-mucus glycoproteins 59:89 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 59:132 Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 3345749 5 83 theme core 1103:1106 arg1 type 1108:1111 core type 1 1103:1113 core type 1 1103:1113 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 2 84 theme beta 323:326 arg1 core 366:369 the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core 315:369 the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2) 315:378 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 84 theme beta 323:326 arg1 type 372:375 type 2 372:377 type 2 372:377 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 5 85 theme Gal 984:986 arg1 1----3 993:998 1----3 993:998 1----3 993:998 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 5 85 theme Gal 984:986 arg1 beta 988:991 Gal beta 984:991 Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively) 984:1128 Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1----3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. 3345749 6 86 dep cores 1195:1199 arg1 2 1202:1202 2 1202:1202 2 1202:1202 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 2 87 theme [GlcNAc 335:341 arg1 beta 323:326 Gal beta 319:326 the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2) 315:378 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 2 87 theme [GlcNAc 335:341 arg1 beta 343:346 1----3)[GlcNAc beta(1----6) 328:354 1----3)[GlcNAc beta(1----6) 328:354 Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). 3345749 6 88 theme cystic 1332:1337 arg1 [Lamblin 1348:1355 cystic fibrosis [Lamblin 1332:1355 cystic fibrosis [Lamblin 1332:1355 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 88 theme cystic 1332:1337 arg1 J.F.G. 1457:1462 J.F.G. 1457:1462 J.F.G. 1457:1462 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 6 88 theme cystic 1332:1337 arg1 H. 1436:1437 H. 1436:1437 H. 1436:1437 Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. 3345749 4 89 with other 716:720 arg1 groups 737:742 octadecyl groups 727:742 octadecyl groups 727:742 Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 11479274 7 0 from alterations 1585:1595 arg1 glycosylation 1600:1612 glycosylation 1600:1612 glycosylation 1600:1612 Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases. 11479274 6 1 theme chains 1384:1389 arg1 number 1358:1363 the number 1354:1363 the number of oligosaccharide chains 1354:1389 However, no decrease in the number of oligosaccharide chains was indicated. 11479274 5 2 theme pathway 1264:1270 arg1 neutralization 1232:1245 neutralization 1232:1245 neutralization of the secretory pathway 1232:1270 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 1 3 theme weak 152:155 arg1 NH4Cl 181:185 NH4Cl 181:185 NH4Cl 181:185 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 1 3 theme weak 152:155 arg1 chloride 171:178 the weak base ammonium chloride 148:178 the weak base ammonium chloride (NH4Cl) 148:186 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 7 4 theme altered 1564:1570 arg1 pH 1572:1573 altered pH 1564:1573 altered pH 1564:1573 Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases. 11479274 6 5 from decrease 1342:1349 arg1 number 1358:1363 the number 1354:1363 the number of oligosaccharide chains 1354:1389 However, no decrease in the number of oligosaccharide chains was indicated. 11479274 0 6 theme glycosyltransferases 69:88 arg1 redistribution 51:64 redistribution 51:64 redistribution of glycosyltransferases and changes 51:100 Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins. 11479274 1 7 theme secretory 314:322 arg1 pathway 324:330 the secretory pathway 310:330 the secretory pathway 310:330 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 4 8 theme general 925:931 arg1 morphology 933:942 The general morphology 921:942 The general morphology of the endoplasmic reticulum and Golgi apparatus 921:991 The general morphology of the endoplasmic reticulum and Golgi apparatus was retained as judged from immunofluorescence and electron microscopy studies. 11479274 1 9 theme base 157:160 arg1 NH4Cl 181:185 NH4Cl 181:185 NH4Cl 181:185 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 1 9 theme base 157:160 arg1 chloride 171:178 the weak base ammonium chloride 148:178 the weak base ammonium chloride (NH4Cl) 148:186 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 1 10 theme cultured 235:242 arg1 cells 261:265 cultured HeLa and LS 174T cells 235:265 cultured HeLa and LS 174T cells 235:265 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 2 11 theme Golgi 551:555 arg1 stack 557:561 the Golgi stack 547:561 the Golgi stack 547:561 This resulted in relocalization of the three studied glycosyltransferases, N-acetylgalactosaminyltransferase 2, beta1,2 N-acetylglucosaminyltransferase I, and beta1,4 galactosyltransferase 1, normally localized to the Golgi stack, the medial/trans-Golgi and the trans-Golgi/TGN, respectively. 11479274 0 12 from Neutralization 0:13 arg1 apparatus 34:42 the Golgi apparatus 24:42 the Golgi apparatus 24:42 Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins. 11479274 7 13 theme contributing 1449:1460 arg1 factor 1462:1467 a contributing factor 1447:1467 a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus 1447:1553 Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases. 11479274 7 13 theme contributing 1449:1460 arg1 pH 1441:1442 pH 1441:1442 pH 1441:1442 Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases. 11479274 7 14 theme Golgi 1539:1543 arg1 apparatus 1545:1553 the Golgi apparatus 1535:1553 the Golgi apparatus 1535:1553 Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases. 11479274 1 15 theme HeLa 244:247 arg1 cells 261:265 cultured HeLa and LS 174T cells 235:265 cultured HeLa and LS 174T cells 235:265 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 0 16 theme changes 94:100 arg1 redistribution 51:64 redistribution 51:64 redistribution of glycosyltransferases and changes 51:100 Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins. 11479274 3 17 theme native 740:745 arg1 glycosyltransferases 747:766 the tagged or native glycosyltransferases 726:766 the tagged or native glycosyltransferases 726:766 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 5 18 from O-glycans 1082:1090 arg1 mucins 1142:1147 the guanidinium chloride insoluble gel-forming mucins 1095:1147 the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells 1095:1170 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 5 19 from cells 1166:1170 arg1 mucins 1142:1147 the guanidinium chloride insoluble gel-forming mucins 1095:1147 the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells 1095:1170 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 7 20 theme proper 1473:1478 arg1 distribution 1493:1504 proper steady-state distribution 1473:1504 proper steady-state distribution of glycosyltransferases over the Golgi apparatus 1473:1553 Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases. 11479274 7 21 theme glycosyltransferases 1509:1528 arg1 distribution 1493:1504 proper steady-state distribution 1473:1504 proper steady-state distribution of glycosyltransferases over the Golgi apparatus 1473:1553 Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases. 11479274 1 22 theme ammonium 162:169 arg1 NH4Cl 181:185 NH4Cl 181:185 NH4Cl 181:185 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 1 22 theme ammonium 162:169 arg1 chloride 171:178 the weak base ammonium chloride 148:178 the weak base ammonium chloride (NH4Cl) 148:186 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 5 23 theme gas 1189:1191 arg1 spectrometry 1213:1224 gas chromatography-mass spectrometry 1189:1224 gas chromatography-mass spectrometry 1189:1224 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 2 24 theme beta1,4 492:498 arg1 galactosyltransferase 500:520 beta1,4 galactosyltransferase 1 492:522 beta1,4 galactosyltransferase 1 492:522 This resulted in relocalization of the three studied glycosyltransferases, N-acetylgalactosaminyltransferase 2, beta1,2 N-acetylglucosaminyltransferase I, and beta1,4 galactosyltransferase 1, normally localized to the Golgi stack, the medial/trans-Golgi and the trans-Golgi/TGN, respectively. 11479274 3 25 theme bafilomycin 871:881 arg1 A1 883:884 bafilomycin A1 871:884 bafilomycin A1 871:884 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 1 26 theme chloride 171:178 arg1 Addition 136:143 Addition 136:143 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells 136:265 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 5 27 theme chromatography-mass 1193:1211 arg1 spectrometry 1213:1224 gas chromatography-mass spectrometry 1189:1224 gas chromatography-mass spectrometry 1189:1224 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 3 28 theme enzymes 817:823 arg1 relocalization 795:808 a relocalization 793:808 a relocalization of the enzymes mainly to vesicles of endosomal type 793:860 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 3 29 theme glycosyltransferases 747:766 arg1 fractionation 709:721 subcellular fractionation 697:721 subcellular fractionation 697:721 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 3 29 theme glycosyltransferases 747:766 arg1 microscopy 654:663 Indirect immunofluorescence microscopy 626:663 Indirect immunofluorescence microscopy 626:663 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 3 29 theme glycosyltransferases 747:766 arg1 microscopy 681:690 immunoelectron microscopy 666:690 immunoelectron microscopy 666:690 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 2 30 theme beta1,2 445:451 arg1 N-acetylglucosaminyltransferase 453:483 beta1,2 N-acetylglucosaminyltransferase I 445:485 beta1,2 N-acetylglucosaminyltransferase I 445:485 This resulted in relocalization of the three studied glycosyltransferases, N-acetylgalactosaminyltransferase 2, beta1,2 N-acetylglucosaminyltransferase I, and beta1,4 galactosyltransferase 1, normally localized to the Golgi stack, the medial/trans-Golgi and the trans-Golgi/TGN, respectively. 11479274 1 31 theme LS 253:254 arg1 cells 261:265 cultured HeLa and LS 174T cells 235:265 cultured HeLa and LS 174T cells 235:265 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 5 32 theme gel-forming 1130:1140 arg1 mucins 1142:1147 the guanidinium chloride insoluble gel-forming mucins 1095:1147 the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells 1095:1170 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 6 33 theme oligosaccharide 1368:1382 arg1 chains 1384:1389 oligosaccharide chains 1368:1389 oligosaccharide chains 1368:1389 However, no decrease in the number of oligosaccharide chains was indicated. 11479274 1 34 theme 174T 256:259 arg1 cells 261:265 cultured HeLa and LS 174T cells 235:265 cultured HeLa and LS 174T cells 235:265 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 0 35 theme mucins 128:133 arg1 O-glycosylation 109:123 the O-glycosylation 105:123 the O-glycosylation of mucins 105:133 Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins. 11479274 7 36 theme steady-state 1480:1491 arg1 distribution 1493:1504 proper steady-state distribution 1473:1504 proper steady-state distribution of glycosyltransferases over the Golgi apparatus 1473:1553 Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases. 11479274 0 37 theme pH 18:19 arg1 Neutralization 0:13 Neutralization 0:13 Neutralization of pH in the Golgi apparatus 0:42 Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins. 11479274 4 38 theme apparatus 983:991 arg1 morphology 933:942 The general morphology 921:942 The general morphology of the endoplasmic reticulum and Golgi apparatus 921:991 The general morphology of the endoplasmic reticulum and Golgi apparatus was retained as judged from immunofluorescence and electron microscopy studies. 11479274 3 39 theme subcellular 697:707 arg1 fractionation 709:721 subcellular fractionation 697:721 subcellular fractionation 697:721 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 0 40 gly O-glycosylation 109:123 arg1 mucins 128:133 mucins 128:133 mucins 128:133 Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins. 11479274 0 41 theme Golgi 28:32 arg1 apparatus 34:42 the Golgi apparatus 24:42 the Golgi apparatus 24:42 Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins. 11479274 5 42 theme 174T 1161:1164 arg1 cells 1166:1170 the LS 174T cells 1154:1170 the LS 174T cells 1154:1170 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 3 43 theme Indirect 626:633 arg1 microscopy 654:663 Indirect immunofluorescence microscopy 626:663 Indirect immunofluorescence microscopy 626:663 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 2 44 theme glycosyltransferases 386:405 arg1 relocalization 350:363 relocalization 350:363 relocalization of the three studied glycosyltransferases 350:405 This resulted in relocalization of the three studied glycosyltransferases, N-acetylgalactosaminyltransferase 2, beta1,2 N-acetylglucosaminyltransferase I, and beta1,4 galactosyltransferase 1, normally localized to the Golgi stack, the medial/trans-Golgi and the trans-Golgi/TGN, respectively. 11479274 2 44 theme glycosyltransferases 386:405 arg1 N-acetylglucosaminyltransferase 453:483 beta1,2 N-acetylglucosaminyltransferase I 445:485 beta1,2 N-acetylglucosaminyltransferase I 445:485 This resulted in relocalization of the three studied glycosyltransferases, N-acetylgalactosaminyltransferase 2, beta1,2 N-acetylglucosaminyltransferase I, and beta1,4 galactosyltransferase 1, normally localized to the Golgi stack, the medial/trans-Golgi and the trans-Golgi/TGN, respectively. 11479274 2 44 theme glycosyltransferases 386:405 arg1 galactosyltransferase 500:520 beta1,4 galactosyltransferase 1 492:522 beta1,4 galactosyltransferase 1 492:522 This resulted in relocalization of the three studied glycosyltransferases, N-acetylgalactosaminyltransferase 2, beta1,2 N-acetylglucosaminyltransferase I, and beta1,4 galactosyltransferase 1, normally localized to the Golgi stack, the medial/trans-Golgi and the trans-Golgi/TGN, respectively. 11479274 2 44 theme glycosyltransferases 386:405 arg1 N-acetylgalactosaminyltransferase 408:440 N-acetylgalactosaminyltransferase 2 408:442 N-acetylgalactosaminyltransferase 2 408:442 This resulted in relocalization of the three studied glycosyltransferases, N-acetylgalactosaminyltransferase 2, beta1,2 N-acetylglucosaminyltransferase I, and beta1,4 galactosyltransferase 1, normally localized to the Golgi stack, the medial/trans-Golgi and the trans-Golgi/TGN, respectively. 11479274 3 45 theme cell 898:901 arg1 staining 911:918 cell surface staining 898:918 cell surface staining 898:918 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 5 46 theme shorter 1297:1303 arg1 O-glycans 1305:1313 10 days shorter O-glycans 1289:1313 10 days shorter O-glycans 1289:1313 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 3 47 theme immunofluorescence 635:652 arg1 microscopy 654:663 Indirect immunofluorescence microscopy 626:663 Indirect immunofluorescence microscopy 626:663 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 1 48 theme proton 195:200 arg1 A1 229:230 the proton pump inhibitor bafilomycin A1 191:230 the proton pump inhibitor bafilomycin A1 191:230 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 5 49 theme LS 1158:1159 arg1 cells 1166:1170 the LS 174T cells 1154:1170 the LS 174T cells 1154:1170 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 3 50 theme endosomal 847:855 arg1 type 857:860 endosomal type 847:860 endosomal type 847:860 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 4 51 theme reticulum 963:971 arg1 morphology 933:942 The general morphology 921:942 The general morphology of the endoplasmic reticulum and Golgi apparatus 921:991 The general morphology of the endoplasmic reticulum and Golgi apparatus was retained as judged from immunofluorescence and electron microscopy studies. 11479274 5 52 theme chloride 1111:1118 arg1 mucins 1142:1147 the guanidinium chloride insoluble gel-forming mucins 1095:1147 the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells 1095:1170 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 1 53 theme pathway 324:330 arg1 gradient 298:305 the pH gradient 291:305 the pH gradient of the secretory pathway 291:330 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 1 54 theme pH 295:296 arg1 gradient 298:305 the pH gradient 291:305 the pH gradient of the secretory pathway 291:330 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 4 55 theme endoplasmic 951:961 arg1 reticulum 963:971 the endoplasmic reticulum 947:971 the endoplasmic reticulum 947:971 The general morphology of the endoplasmic reticulum and Golgi apparatus was retained as judged from immunofluorescence and electron microscopy studies. 11479274 3 56 theme tagged 730:735 arg1 glycosyltransferases 747:766 the tagged or native glycosyltransferases 726:766 the tagged or native glycosyltransferases 726:766 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 5 57 theme insoluble 1120:1128 arg1 mucins 1142:1147 the guanidinium chloride insoluble gel-forming mucins 1095:1147 the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells 1095:1170 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 7 58 theme glycosyltransferases 1650:1669 arg1 relocalization 1632:1645 a relocalization 1630:1645 a relocalization of glycosyltransferases 1630:1669 Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases. 11479274 4 59 theme Golgi 977:981 arg1 apparatus 983:991 Golgi apparatus 977:991 Golgi apparatus 977:991 The general morphology of the endoplasmic reticulum and Golgi apparatus was retained as judged from immunofluorescence and electron microscopy studies. 11479274 3 60 theme immunoelectron 666:679 arg1 microscopy 681:690 immunoelectron microscopy 666:690 immunoelectron microscopy 666:690 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 5 61 theme guanidinium 1099:1109 arg1 mucins 1142:1147 the guanidinium chloride insoluble gel-forming mucins 1095:1147 the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells 1095:1170 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 1 62 theme pump 202:205 arg1 A1 229:230 the proton pump inhibitor bafilomycin A1 191:230 the proton pump inhibitor bafilomycin A1 191:230 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 3 63 theme surface 903:909 arg1 staining 911:918 cell surface staining 898:918 cell surface staining 898:918 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 1 64 theme inhibitor 207:215 arg1 A1 229:230 the proton pump inhibitor bafilomycin A1 191:230 the proton pump inhibitor bafilomycin A1 191:230 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 2 65 theme studied 378:384 arg1 glycosyltransferases 386:405 the three studied glycosyltransferases 368:405 the three studied glycosyltransferases 368:405 This resulted in relocalization of the three studied glycosyltransferases, N-acetylgalactosaminyltransferase 2, beta1,2 N-acetylglucosaminyltransferase I, and beta1,4 galactosyltransferase 1, normally localized to the Golgi stack, the medial/trans-Golgi and the trans-Golgi/TGN, respectively. 11479274 4 66 dep immunofluorescence 1021:1038 arg1 studies 1064:1070 studies 1064:1070 studies 1064:1070 The general morphology of the endoplasmic reticulum and Golgi apparatus was retained as judged from immunofluorescence and electron microscopy studies. 11479274 3 67 theme type 857:860 arg1 vesicles 835:842 vesicles 835:842 vesicles of endosomal type 835:860 Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. 11479274 1 68 theme bafilomycin 217:227 arg1 A1 229:230 the proton pump inhibitor bafilomycin A1 191:230 the proton pump inhibitor bafilomycin A1 191:230 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 11479274 4 69 theme electron 1044:1051 arg1 microscopy 1053:1062 electron microscopy 1044:1062 electron microscopy 1044:1062 The general morphology of the endoplasmic reticulum and Golgi apparatus was retained as judged from immunofluorescence and electron microscopy studies. 11479274 5 70 theme secretory 1254:1262 arg1 pathway 1264:1270 the secretory pathway 1250:1270 the secretory pathway 1250:1270 When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. 11479274 1 71 theme A1 229:230 arg1 Addition 136:143 Addition 136:143 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells 136:265 Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. 14673092 0 0 theme identical 66:74 arg1 O-glycans 76:84 identical O-glycans 66:84 identical O-glycans 66:84 Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans. 14673092 7 1 theme beta-linked 1037:1047 arg1 N-acetylhexosamine 1049:1066 beta-linked N-acetylhexosamine 1037:1066 beta-linked N-acetylhexosamine 1037:1066 Core type 1 O-glycans are also present and are generally unmodified, although some are terminated with sialic acid, beta-linked N-acetylhexosamine, or NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4. 14673092 9 2 theme huZP3-associated 1305:1320 arg1 O-glycans 1322:1330 huZP3-associated O-glycans 1305:1330 huZP3-associated O-glycans 1305:1330 Sequencing of huZP3-associated O-glycans confirms that this implication is correct. 14673092 4 3 theme glycoproteins 520:532 arg1 O-glycosylation 482:496 the O-glycosylation 478:496 the O-glycosylation of the individual mZP glycoproteins 478:532 In this study, we analyzed the O-glycosylation of the individual mZP glycoproteins by using ultrasensitive MS methods. 14673092 4 4 theme mZP 516:518 arg1 glycoproteins 520:532 the individual mZP glycoproteins 501:532 the individual mZP glycoproteins 501:532 In this study, we analyzed the O-glycosylation of the individual mZP glycoproteins by using ultrasensitive MS methods. 14673092 10 5 theme initial 1499:1505 arg1 binding 1524:1530 initial murine sperm-egg binding 1499:1530 initial murine sperm-egg binding 1499:1530 The data obtained in this investigation may prove to be very useful for studies to determine the precise molecular basis of initial murine sperm-egg binding. 14673092 8 6 gly glycoprotein 1144:1155 arg1 glycoprotein 1144:1155 human ZP (huZP) glycoprotein huZP3 1128:1161 human ZP (huZP) glycoprotein huZP3 1128:1161 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 10 7 theme precise 1472:1478 arg1 basis 1490:1494 the precise molecular basis 1468:1494 the precise molecular basis of initial murine sperm-egg binding 1468:1530 The data obtained in this investigation may prove to be very useful for studies to determine the precise molecular basis of initial murine sperm-egg binding. 14673092 8 8 theme same 1260:1263 arg1 O-glycans 1265:1273 the same O-glycans 1256:1273 the same O-glycans 1256:1273 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 10 9 theme binding 1524:1530 arg1 basis 1490:1494 the precise molecular basis 1468:1494 the precise molecular basis of initial murine sperm-egg binding 1468:1530 The data obtained in this investigation may prove to be very useful for studies to determine the precise molecular basis of initial murine sperm-egg binding. 14673092 5 10 theme O-glycans 604:612 arg1 sequences 654:662 core type 2 sequences 642:662 core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen) 642:824 We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). 14673092 5 10 theme O-glycans 604:612 arg1 majority 588:595 the majority 584:595 the majority of the O-glycans that are linked to mZP3 584:636 We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). 14673092 8 11 attach derived 1164:1170 arg2 huZP3 1157:1161 human ZP (huZP) glycoprotein huZP3 1128:1161 human ZP (huZP) glycoprotein huZP3 1128:1161 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 8 11 attach derived 1164:1170 arg1 mice 1188:1191 transgenic mice 1177:1191 transgenic mice 1177:1191 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 8 12 theme human 1214:1218 arg1 sperm 1220:1224 murine but not human sperm 1199:1224 murine but not human sperm 1199:1224 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 2 13 theme plasma 362:367 arg1 membrane 369:376 the sperm plasma membrane 352:376 the sperm plasma membrane 352:376 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 2 14 theme egg-binding 323:333 arg1 proteins 335:342 egg-binding proteins 323:342 egg-binding proteins coating the sperm plasma membrane 323:376 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 3 15 theme precise 383:389 arg1 basis 401:405 The precise molecular basis 379:405 The precise molecular basis of this interaction 379:425 The precise molecular basis of this interaction remains to be resolved. 14673092 10 16 theme molecular 1480:1488 arg1 basis 1490:1494 the precise molecular basis 1468:1494 the precise molecular basis of initial murine sperm-egg binding 1468:1530 The data obtained in this investigation may prove to be very useful for studies to determine the precise molecular basis of initial murine sperm-egg binding. 14673092 7 17 theme sialic 1024:1029 arg1 acid 1031:1034 sialic acid 1024:1034 sialic acid 1024:1034 Core type 1 O-glycans are also present and are generally unmodified, although some are terminated with sialic acid, beta-linked N-acetylhexosamine, or NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4. 14673092 8 18 theme human 1128:1132 arg1 huZP 1138:1141 huZP 1138:1141 huZP 1138:1141 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 8 18 theme human 1128:1132 arg1 ZP 1134:1135 human ZP 1128:1135 human ZP (huZP) glycoprotein huZP3 1128:1161 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 3 19 theme molecular 391:399 arg1 basis 401:405 The precise molecular basis 379:405 The precise molecular basis of this interaction 379:425 The precise molecular basis of this interaction remains to be resolved. 14673092 8 20 theme ZP 1134:1135 arg1 huZP3 1157:1161 human ZP (huZP) glycoprotein huZP3 1128:1161 human ZP (huZP) glycoprotein huZP3 1128:1161 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 4 21 gly glycoproteins 520:532 arg1 glycoproteins 520:532 the individual mZP glycoproteins 501:532 the individual mZP glycoproteins 501:532 In this study, we analyzed the O-glycosylation of the individual mZP glycoproteins by using ultrasensitive MS methods. 14673092 1 22 theme egg 163:165 arg1 outer 141:145 outer 141:145 outer 141:145 Murine sperm initiate fertilization by binding to the outer covering of the egg known as the murine zona pellucida (mZP). 14673092 0 23 theme Murine 0:5 arg1 pellucida 22:30 Murine and human zona pellucida 3 0:32 Murine and human zona pellucida 3 derived from mouse eggs 0:56 Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans. 14673092 5 24 theme core 642:645 arg1 type 647:650 core type 2 642:652 core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen) 642:824 We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). 14673092 0 25 attach derived 34:40 arg2 pellucida 22:30 Murine and human zona pellucida 3 0:32 Murine and human zona pellucida 3 derived from mouse eggs 0:56 Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans. 14673092 0 25 attach derived 34:40 arg1 eggs 53:56 mouse eggs 47:56 mouse eggs 47:56 Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans. 14673092 2 26 theme O-glycans 263:271 arg1 interaction 248:258 the interaction 244:258 the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane 244:376 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 8 27 theme transgenic 1177:1186 arg1 mice 1188:1191 transgenic mice 1177:1191 transgenic mice 1177:1191 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 0 28 theme zona 17:20 arg1 pellucida 22:30 Murine and human zona pellucida 3 0:32 Murine and human zona pellucida 3 derived from mouse eggs 0:56 Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans. 14673092 2 29 attach linked 273:278 arg2 O-glycans 263:271 O-glycans 263:271 O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane 263:376 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 2 29 attach linked 273:278 arg1 mZP3 312:315 mZP3 312:315 mZP3 312:315 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 2 29 attach linked 273:278 arg1 glycoprotein 298:309 a specific mZP glycoprotein 283:309 a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane 283:376 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 1 30 theme Murine 87:92 arg1 sperm 94:98 Murine sperm 87:98 Murine sperm 87:98 Murine sperm initiate fertilization by binding to the outer covering of the egg known as the murine zona pellucida (mZP). 14673092 0 31 theme human 11:15 arg1 pellucida 22:30 Murine and human zona pellucida 3 0:32 Murine and human zona pellucida 3 derived from mouse eggs 0:56 Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans. 14673092 4 32 theme individual 505:514 arg1 glycoproteins 520:532 the individual mZP glycoproteins 501:532 the individual mZP glycoproteins 501:532 In this study, we analyzed the O-glycosylation of the individual mZP glycoproteins by using ultrasensitive MS methods. 14673092 3 33 theme interaction 415:425 arg1 basis 401:405 The precise molecular basis 379:405 The precise molecular basis of this interaction 379:425 The precise molecular basis of this interaction remains to be resolved. 14673092 8 34 theme glycoprotein 1144:1155 arg1 huZP3 1157:1161 human ZP (huZP) glycoprotein huZP3 1128:1161 human ZP (huZP) glycoprotein huZP3 1128:1161 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 2 35 gly glycoprotein 298:309 arg1 mZP3 312:315 mZP3 312:315 mZP3 312:315 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 2 35 gly glycoprotein 298:309 arg1 glycoprotein 298:309 a specific mZP glycoprotein 283:309 a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane 283:376 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 1 36 theme murine 180:185 arg1 mZP 203:205 mZP 203:205 mZP 203:205 Murine sperm initiate fertilization by binding to the outer covering of the egg known as the murine zona pellucida (mZP). 14673092 1 36 theme murine 180:185 arg1 pellucida 192:200 the murine zona pellucida 176:200 the murine zona pellucida (mZP) 176:206 Murine sperm initiate fertilization by binding to the outer covering of the egg known as the murine zona pellucida (mZP). 14673092 5 37 attach linked 623:628 arg2 O-glycans 604:612 the O-glycans 600:612 the O-glycans that are linked to mZP3 600:636 We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). 14673092 5 37 attach linked 623:628 arg1 mZP3 633:636 mZP3 633:636 mZP3 633:636 We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). 14673092 2 38 theme sperm 356:360 arg1 membrane 369:376 the sperm plasma membrane 352:376 the sperm plasma membrane 352:376 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 10 39 theme murine 1507:1512 arg1 binding 1524:1530 initial murine sperm-egg binding 1499:1530 initial murine sperm-egg binding 1499:1530 The data obtained in this investigation may prove to be very useful for studies to determine the precise molecular basis of initial murine sperm-egg binding. 14673092 5 40 theme type 647:650 arg1 sequences 654:662 core type 2 sequences 642:662 core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen) 642:824 We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). 14673092 5 40 theme type 647:650 arg1 majority 588:595 the majority 584:595 the majority of the O-glycans that are linked to mZP3 584:636 We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). 14673092 10 41 theme sperm-egg 1514:1522 arg1 binding 1524:1530 initial murine sperm-egg binding 1499:1530 initial murine sperm-egg binding 1499:1530 The data obtained in this investigation may prove to be very useful for studies to determine the precise molecular basis of initial murine sperm-egg binding. 14673092 4 42 gly O-glycosylation 482:496 arg1 glycoproteins 520:532 the individual mZP glycoproteins 501:532 the individual mZP glycoproteins 501:532 In this study, we analyzed the O-glycosylation of the individual mZP glycoproteins by using ultrasensitive MS methods. 14673092 4 42 gly O-glycosylation 482:496 arg1 study 459:463 this study 454:463 this study 454:463 In this study, we analyzed the O-glycosylation of the individual mZP glycoproteins by using ultrasensitive MS methods. 14673092 1 43 theme zona 187:190 arg1 mZP 203:205 mZP 203:205 mZP 203:205 Murine sperm initiate fertilization by binding to the outer covering of the egg known as the murine zona pellucida (mZP). 14673092 1 43 theme zona 187:190 arg1 pellucida 192:200 the murine zona pellucida 176:200 the murine zona pellucida (mZP) 176:206 Murine sperm initiate fertilization by binding to the outer covering of the egg known as the murine zona pellucida (mZP). 14673092 6 44 theme murine 895:900 arg1 binding 912:918 murine sperm-egg binding 895:918 murine sperm-egg binding 895:918 Many of these terminal sequences have been implicated previously in murine sperm-egg binding. 14673092 8 45 theme native 1278:1283 arg1 mZP3 1285:1288 native mZP3 1278:1288 native mZP3 1278:1288 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 2 46 theme mZP 294:296 arg1 mZP3 312:315 mZP3 312:315 mZP3 312:315 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 2 46 theme mZP 294:296 arg1 glycoprotein 298:309 a specific mZP glycoprotein 283:309 a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane 283:376 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 2 47 theme specific 285:292 arg1 mZP3 312:315 mZP3 312:315 mZP3 312:315 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 2 47 theme specific 285:292 arg1 glycoprotein 298:309 a specific mZP glycoprotein 283:309 a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane 283:376 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 6 48 theme sequences 850:858 arg1 sequences 850:858 these terminal sequences 835:858 these terminal sequences 835:858 Many of these terminal sequences have been implicated previously in murine sperm-egg binding. 14673092 6 48 theme sequences 850:858 arg1 Many 827:830 Many 827:830 Many 827:830 Many of these terminal sequences have been implicated previously in murine sperm-egg binding. 14673092 7 49 link beta-linked 1037:1047 arg1 N-acetylhexosamine 1049:1066 beta-linked N-acetylhexosamine 1037:1066 beta-linked N-acetylhexosamine 1037:1066 Core type 1 O-glycans are also present and are generally unmodified, although some are terminated with sialic acid, beta-linked N-acetylhexosamine, or NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4. 14673092 2 50 with glycoprotein 298:309 arg1 proteins 335:342 egg-binding proteins 323:342 egg-binding proteins coating the sperm plasma membrane 323:376 This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. 14673092 4 51 theme MS 558:559 arg1 methods 561:567 ultrasensitive MS methods 543:567 ultrasensitive MS methods 543:567 In this study, we analyzed the O-glycosylation of the individual mZP glycoproteins by using ultrasensitive MS methods. 14673092 7 52 theme Core 921:924 arg1 type 926:929 Core type 1 921:931 Core type 1 O-glycans 921:941 Core type 1 O-glycans are also present and are generally unmodified, although some are terminated with sialic acid, beta-linked N-acetylhexosamine, or NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4. 14673092 4 53 theme ultrasensitive 543:556 arg1 methods 561:567 ultrasensitive MS methods 543:567 ultrasensitive MS methods 543:567 In this study, we analyzed the O-glycosylation of the individual mZP glycoproteins by using ultrasensitive MS methods. 14673092 5 54 theme sialic 680:685 arg1 acid 687:690 sialic acid 680:690 sialic acid 680:690 We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). 14673092 8 55 theme murine 1199:1204 arg1 sperm 1220:1224 murine but not human sperm 1199:1224 murine but not human sperm 1199:1224 Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. 14673092 7 56 theme type 926:929 arg1 O-glycans 933:941 Core type 1 O-glycans 921:941 Core type 1 O-glycans 921:941 Core type 1 O-glycans are also present and are generally unmodified, although some are terminated with sialic acid, beta-linked N-acetylhexosamine, or NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4. 14673092 5 57 theme Sda 813:815 arg1 Galbeta1-4 801:810 NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 773:810 NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen) 773:824 We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). 14673092 5 57 theme Sda 813:815 arg1 antigen 817:823 Sda antigen 813:823 Sda antigen 813:823 We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). 14673092 9 58 theme O-glycans 1322:1330 arg1 Sequencing 1291:1300 Sequencing 1291:1300 Sequencing of huZP3-associated O-glycans 1291:1330 Sequencing of huZP3-associated O-glycans confirms that this implication is correct. 14673092 0 59 theme mouse 47:51 arg1 eggs 53:56 mouse eggs 47:56 mouse eggs 47:56 Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans. 14673092 6 60 theme terminal 841:848 arg1 sequences 850:858 these terminal sequences 835:858 these terminal sequences 835:858 Many of these terminal sequences have been implicated previously in murine sperm-egg binding. 14673092 6 61 theme sperm-egg 902:910 arg1 binding 912:918 murine sperm-egg binding 895:918 murine sperm-egg binding 895:918 Many of these terminal sequences have been implicated previously in murine sperm-egg binding. 8620897 10 0 theme High-mannose-type 1098:1114 arg1 oligosaccharides 1116:1131 High-mannose-type oligosaccharides 1098:1131 High-mannose-type oligosaccharides 1098:1131 High-mannose-type oligosaccharides accounted for only 1.5% of the total. 8620897 5 1 theme HPLC 672:675 arg1 columns 677:683 HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 672:765 HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 672:765 The pyridylamino-oligosaccharides were separated and these structures were identified by a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. 8620897 3 2 from almond 432:437 arg1 digestion 396:404 digestion 396:404 digestion with glycoamidase A (from almond) 396:438 N-linked oligosaccharides were released from the glycopeptides by digestion with glycoamidase A (from almond). 8620897 9 3 theme neutral 965:971 arg1 oligosaccharides 1026:1041 neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 965:1041 neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 965:1041 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides was 20.8%, 24.8%, 27.7%, 18.1% and 8.6%, respectively. 8620897 5 4 theme columns 677:683 arg1 kinds 663:667 three kinds 657:667 three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 657:765 The pyridylamino-oligosaccharides were separated and these structures were identified by a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. 8620897 5 5 theme three-dimensional 613:629 arg1 technique 644:652 a three-dimensional HPLC mapping technique 611:652 a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 611:765 The pyridylamino-oligosaccharides were separated and these structures were identified by a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. 8620897 1 6 theme human 174:178 arg1 beta 197:200 human integrin alpha 5 beta 1 174:202 human integrin alpha 5 beta 1 174:202 Structures of N-linked oligosaccharides obtained from human integrin alpha 5 beta 1 are described. 8620897 0 7 theme three-dimensional 83:99 arg1 technique 109:117 a three-dimensional mapping technique 81:117 a three-dimensional mapping technique 81:117 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 analyzed by a three-dimensional mapping technique. 8620897 5 8 theme HPLC 631:634 arg1 technique 644:652 a three-dimensional HPLC mapping technique 611:652 a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 611:765 The pyridylamino-oligosaccharides were separated and these structures were identified by a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. 8620897 9 9 theme mono-sialyl 974:984 arg1 oligosaccharides 1026:1041 neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 965:1041 neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 965:1041 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides was 20.8%, 24.8%, 27.7%, 18.1% and 8.6%, respectively. 8620897 13 10 theme reducing 1457:1464 arg1 end 1466:1468 the reducing end 1453:1468 the reducing end 1453:1468 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 3 11 with digestion 396:404 arg1 A 424:424 glycoamidase A 411:424 glycoamidase A 411:424 N-linked oligosaccharides were released from the glycopeptides by digestion with glycoamidase A (from almond). 8620897 5 12 theme mapping 636:642 arg1 technique 644:652 a three-dimensional HPLC mapping technique 611:652 a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 611:765 The pyridylamino-oligosaccharides were separated and these structures were identified by a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. 8620897 3 13 link N-linked 330:337 arg1 oligosaccharides 339:354 N-linked oligosaccharides 330:354 N-linked oligosaccharides 330:354 N-linked oligosaccharides were released from the glycopeptides by digestion with glycoamidase A (from almond). 8620897 8 14 theme different 804:812 arg1 structures 830:839 35 different oligosaccharide structures 801:839 35 different oligosaccharide structures 801:839 Finally, 35 different oligosaccharide structures were identified, 10 of which were neutral, 6 mono-sialyl, 10 di-sialyl, 7 tri-sialyl and 2 tetra-sialyl. 8620897 9 15 theme tri-sialyl 998:1007 arg1 oligosaccharides 1026:1041 neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 965:1041 neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 965:1041 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides was 20.8%, 24.8%, 27.7%, 18.1% and 8.6%, respectively. 8620897 3 16 gly glycopeptides 379:391 arg2 glycopeptides 379:391 the glycopeptides 375:391 the glycopeptides 375:391 N-linked oligosaccharides were released from the glycopeptides by digestion with glycoamidase A (from almond). 8620897 12 17 theme -sialyl 1290:1296 arg1 fucosyl 1298:1304 the diantennary di-alpha-(2,3)-sialyl fucosyl 1260:1304 the diantennary di-alpha-(2,3)-sialyl fucosyl 1260:1304 The most predominant structure was the diantennary di-alpha-(2,3)-sialyl fucosyl. 8620897 12 17 theme -sialyl 1290:1296 arg1 structure 1246:1254 The most predominant structure 1225:1254 The most predominant structure 1225:1254 The most predominant structure was the diantennary di-alpha-(2,3)-sialyl fucosyl. 8620897 9 18 theme di-sialyl 987:995 arg1 oligosaccharides 1026:1041 neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 965:1041 neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 965:1041 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides was 20.8%, 24.8%, 27.7%, 18.1% and 8.6%, respectively. 8620897 1 19 theme integrin 180:187 arg1 beta 197:200 human integrin alpha 5 beta 1 174:202 human integrin alpha 5 beta 1 174:202 Structures of N-linked oligosaccharides obtained from human integrin alpha 5 beta 1 are described. 8620897 0 20 theme mapping 101:107 arg1 technique 109:117 a three-dimensional mapping technique 81:117 a three-dimensional mapping technique 81:117 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 analyzed by a three-dimensional mapping technique. 8620897 4 21 theme oligosaccharides 466:481 arg1 ends 454:457 The reducing ends 441:457 The reducing ends of the oligosaccharides 441:481 The reducing ends of the oligosaccharides were derivatized with 2-aminopyridine. 8620897 1 22 theme alpha 189:193 arg1 beta 197:200 human integrin alpha 5 beta 1 174:202 human integrin alpha 5 beta 1 174:202 Structures of N-linked oligosaccharides obtained from human integrin alpha 5 beta 1 are described. 8620897 0 23 theme oligosaccharide 9:23 arg1 structures 25:34 Detailed oligosaccharide structures 0:34 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 0:67 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 analyzed by a three-dimensional mapping technique. 8620897 8 24 theme oligosaccharide 814:828 arg1 structures 830:839 35 different oligosaccharide structures 801:839 35 different oligosaccharide structures 801:839 Finally, 35 different oligosaccharide structures were identified, 10 of which were neutral, 6 mono-sialyl, 10 di-sialyl, 7 tri-sialyl and 2 tetra-sialyl. 8620897 0 25 theme Detailed 0:7 arg1 structures 25:34 Detailed oligosaccharide structures 0:34 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 0:67 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 analyzed by a three-dimensional mapping technique. 8620897 11 26 theme remaining 1175:1183 arg1 type 1219:1222 all complex type 1207:1222 all complex type 1207:1222 The remaining oligosaccharides were all complex type. 8620897 11 26 theme remaining 1175:1183 arg1 oligosaccharides 1185:1200 The remaining oligosaccharides 1171:1200 The remaining oligosaccharides 1171:1200 The remaining oligosaccharides were all complex type. 8620897 13 27 theme N-acetylglucosamine 1422:1440 arg1 residue 1442:1448 the N-acetylglucosamine residue 1418:1448 the N-acetylglucosamine residue of the reducing end 1418:1468 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 13 27 theme N-acetylglucosamine 1422:1440 arg1 end 1466:1468 the reducing end 1453:1468 the reducing end 1453:1468 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 5 28 theme H. 711:712 arg1 Anal 762:765 N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 697:765 N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 697:765 The pyridylamino-oligosaccharides were separated and these structures were identified by a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. 8620897 5 28 theme H. 711:712 arg1 [Takahashi 685:694 [Takahashi 685:694 [Takahashi 685:694 The pyridylamino-oligosaccharides were separated and these structures were identified by a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. 8620897 12 29 theme predominant 1234:1244 arg1 fucosyl 1298:1304 the diantennary di-alpha-(2,3)-sialyl fucosyl 1260:1304 the diantennary di-alpha-(2,3)-sialyl fucosyl 1260:1304 The most predominant structure was the diantennary di-alpha-(2,3)-sialyl fucosyl. 8620897 12 29 theme predominant 1234:1244 arg1 structure 1246:1254 The most predominant structure 1225:1254 The most predominant structure 1225:1254 The most predominant structure was the diantennary di-alpha-(2,3)-sialyl fucosyl. 8620897 9 30 theme tetra-sialyl 1013:1024 arg1 oligosaccharides 1026:1041 neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 965:1041 neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 965:1041 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides was 20.8%, 24.8%, 27.7%, 18.1% and 8.6%, respectively. 8620897 5 31 dep columns 677:683 arg1 Anal 762:765 N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 697:765 N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 697:765 The pyridylamino-oligosaccharides were separated and these structures were identified by a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. 8620897 5 31 dep columns 677:683 arg1 [Takahashi 685:694 [Takahashi 685:694 [Takahashi 685:694 The pyridylamino-oligosaccharides were separated and these structures were identified by a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. 8620897 13 32 theme end 1466:1468 arg1 residue 1442:1448 the N-acetylglucosamine residue 1418:1448 the N-acetylglucosamine residue of the reducing end 1418:1468 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 13 32 theme end 1466:1468 arg1 end 1466:1468 the reducing end 1453:1468 the reducing end 1453:1468 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 2 33 theme human 270:274 arg1 placenta 276:283 human placenta 270:283 human placenta 270:283 Integrin alpha 5 beta 1 (4.5 mg) was purified from human placenta and digested using trypsin and chymotrypsin. 8620897 9 34 theme oligosaccharides 1026:1041 arg1 ratio 956:960 The molar ratio 946:960 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 946:1041 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides was 20.8%, 24.8%, 27.7%, 18.1% and 8.6%, respectively. 8620897 9 34 theme oligosaccharides 1026:1041 arg1 % 1051:1051 20.8% 1047:1051 20.8% 1047:1051 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides was 20.8%, 24.8%, 27.7%, 18.1% and 8.6%, respectively. 8620897 0 35 theme integrin 45:52 arg1 beta 62:65 human integrin alpha 5 beta 1 39:67 human integrin alpha 5 beta 1 39:67 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 analyzed by a three-dimensional mapping technique. 8620897 10 36 theme total 1164:1168 arg1 total 1164:1168 total 1164:1168 total 1164:1168 High-mannose-type oligosaccharides accounted for only 1.5% of the total. 8620897 10 36 theme total 1164:1168 arg1 % 1155:1155 only 1.5% 1147:1155 only 1.5% of the total 1147:1168 High-mannose-type oligosaccharides accounted for only 1.5% of the total. 8620897 13 37 theme oligosaccharides 1381:1396 arg1 % 1372:1372 over 50% 1365:1372 over 50% of all oligosaccharides 1365:1396 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 13 37 theme oligosaccharides 1381:1396 arg1 oligosaccharides 1381:1396 all oligosaccharides 1377:1396 all oligosaccharides 1377:1396 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 0 38 theme human 39:43 arg1 beta 62:65 human integrin alpha 5 beta 1 39:67 human integrin alpha 5 beta 1 39:67 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 analyzed by a three-dimensional mapping technique. 8620897 3 39 theme glycoamidase 411:422 arg1 A 424:424 glycoamidase A 411:424 glycoamidase A 411:424 N-linked oligosaccharides were released from the glycopeptides by digestion with glycoamidase A (from almond). 8620897 4 40 theme reducing 445:452 arg1 ends 454:457 The reducing ends 441:457 The reducing ends of the oligosaccharides 441:481 The reducing ends of the oligosaccharides were derivatized with 2-aminopyridine. 8620897 8 41 theme which 864:868 arg1 which 864:868 which 864:868 which 864:868 Finally, 35 different oligosaccharide structures were identified, 10 of which were neutral, 6 mono-sialyl, 10 di-sialyl, 7 tri-sialyl and 2 tetra-sialyl. 8620897 8 41 theme which 864:868 arg1 10 858:859 10 858:859 10 858:859 Finally, 35 different oligosaccharide structures were identified, 10 of which were neutral, 6 mono-sialyl, 10 di-sialyl, 7 tri-sialyl and 2 tetra-sialyl. 8620897 3 42 theme N-linked 330:337 arg1 oligosaccharides 339:354 N-linked oligosaccharides 330:354 N-linked oligosaccharides 330:354 N-linked oligosaccharides were released from the glycopeptides by digestion with glycoamidase A (from almond). 8620897 2 43 theme alpha 228:232 arg1 beta 236:239 Integrin alpha 5 beta 1 219:241 Integrin alpha 5 beta 1 (4.5 mg) 219:250 Integrin alpha 5 beta 1 (4.5 mg) was purified from human placenta and digested using trypsin and chymotrypsin. 8620897 2 43 theme alpha 228:232 arg1 mg 248:249 4.5 mg 244:249 4.5 mg 244:249 Integrin alpha 5 beta 1 (4.5 mg) was purified from human placenta and digested using trypsin and chymotrypsin. 8620897 0 44 theme alpha 54:58 arg1 beta 62:65 human integrin alpha 5 beta 1 39:67 human integrin alpha 5 beta 1 39:67 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 analyzed by a three-dimensional mapping technique. 8620897 1 45 link N-linked 134:141 arg1 oligosaccharides 143:158 N-linked oligosaccharides 134:158 N-linked oligosaccharides obtained from human integrin alpha 5 beta 1 134:202 Structures of N-linked oligosaccharides obtained from human integrin alpha 5 beta 1 are described. 8620897 2 46 theme Integrin 219:226 arg1 beta 236:239 Integrin alpha 5 beta 1 219:241 Integrin alpha 5 beta 1 (4.5 mg) 219:250 Integrin alpha 5 beta 1 (4.5 mg) was purified from human placenta and digested using trypsin and chymotrypsin. 8620897 2 46 theme Integrin 219:226 arg1 mg 248:249 4.5 mg 244:249 4.5 mg 244:249 Integrin alpha 5 beta 1 (4.5 mg) was purified from human placenta and digested using trypsin and chymotrypsin. 8620897 13 47 theme sialic 1324:1329 arg1 acid 1331:1334 sialic acid 1324:1334 sialic acid 1324:1334 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 13 48 theme acid 1331:1334 arg1 Major 1307:1311 Major 1307:1311 Major 1307:1311 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 1 49 theme N-linked 134:141 arg1 oligosaccharides 143:158 N-linked oligosaccharides 134:158 N-linked oligosaccharides obtained from human integrin alpha 5 beta 1 134:202 Structures of N-linked oligosaccharides obtained from human integrin alpha 5 beta 1 are described. 8620897 9 50 theme molar 950:954 arg1 ratio 956:960 The molar ratio 946:960 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides 946:1041 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides was 20.8%, 24.8%, 27.7%, 18.1% and 8.6%, respectively. 8620897 9 50 theme molar 950:954 arg1 % 1051:1051 20.8% 1047:1051 20.8% 1047:1051 The molar ratio of neutral, mono-sialyl, di-sialyl, tri-sialyl and tetra-sialyl oligosaccharides was 20.8%, 24.8%, 27.7%, 18.1% and 8.6%, respectively. 8620897 3 51 attach released 361:368 arg2 oligosaccharides 339:354 N-linked oligosaccharides 330:354 N-linked oligosaccharides 330:354 N-linked oligosaccharides were released from the glycopeptides by digestion with glycoamidase A (from almond). 8620897 3 51 attach released 361:368 arg1 glycopeptides 379:391 the glycopeptides 375:391 the glycopeptides 375:391 N-linked oligosaccharides were released from the glycopeptides by digestion with glycoamidase A (from almond). 8620897 1 52 theme oligosaccharides 143:158 arg1 Structures 120:129 Structures 120:129 Structures of N-linked oligosaccharides obtained from human integrin alpha 5 beta 1 120:202 Structures of N-linked oligosaccharides obtained from human integrin alpha 5 beta 1 are described. 8620897 0 53 theme beta 62:65 arg1 structures 25:34 Detailed oligosaccharide structures 0:34 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 0:67 Detailed oligosaccharide structures of human integrin alpha 5 beta 1 analyzed by a three-dimensional mapping technique. 8620897 11 54 theme complex 1211:1217 arg1 type 1219:1222 all complex type 1207:1222 all complex type 1207:1222 The remaining oligosaccharides were all complex type. 8620897 11 54 theme complex 1211:1217 arg1 oligosaccharides 1185:1200 The remaining oligosaccharides 1171:1200 The remaining oligosaccharides 1171:1200 The remaining oligosaccharides were all complex type. 8620897 5 55 from technique 644:652 arg1 kinds 663:667 three kinds 657:667 three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal 657:765 The pyridylamino-oligosaccharides were separated and these structures were identified by a three-dimensional HPLC mapping technique on three kinds of HPLC columns [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. 8620897 13 56 gly fucosylated 1403:1413 arg2 end 1466:1468 the reducing end 1453:1468 the reducing end 1453:1468 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 13 56 gly fucosylated 1403:1413 arg1 % 1372:1372 over 50% 1365:1372 over 50% of all oligosaccharides 1365:1396 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 13 56 gly fucosylated 1403:1413 arg1 oligosaccharides 1381:1396 all oligosaccharides 1377:1396 all oligosaccharides 1377:1396 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 8620897 13 56 gly fucosylated 1403:1413 arg2 residue 1442:1448 the N-acetylglucosamine residue 1418:1448 the N-acetylglucosamine residue of the reducing end 1418:1468 Major linking of sialic acid was alpha-(2,3)-linkage, and over 50% of all oligosaccharides were fucosylated at the N-acetylglucosamine residue of the reducing end. 3813552 10 0 theme native 2211:2216 arg1 molecule 2218:2225 the native molecule 2207:2225 the native molecule 2207:2225 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 11 1 contain had 2299:2301 arg1 glycans 2241:2247 These latter glycans 2228:2247 These latter glycans 2228:2247 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 1 contain had 2299:2301 arg2 structure 2317:2325 the following structure 2303:2325 the following structure 2303:2325 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 1 contain had 2299:2301 arg1 alditols 2289:2296 oligosaccharide alditols 2273:2296 oligosaccharide alditols 2273:2296 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 1 2 theme dissociative 234:245 arg1 conditions 247:256 dissociative conditions 234:256 dissociative conditions 234:256 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3813552 10 3 theme chondroitinase 2175:2188 arg1 ABC 2190:2192 chondroitinase ABC 2175:2192 chondroitinase ABC treatment of the native molecule 2175:2225 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 6 4 theme carbohydrate 1269:1280 arg1 chains 1282:1287 The N-glycosidic carbohydrate chains 1252:1287 The N-glycosidic carbohydrate chains 1252:1287 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 4 theme carbohydrate 1269:1280 arg1 glycans 1349:1355 all biantennary glycans 1333:1355 all biantennary glycans containing NeuAc and Fuc 1333:1380 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 4 theme carbohydrate 1269:1280 arg1 glycopeptides 1313:1325 glycopeptides 1313:1325 glycopeptides 1313:1325 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 9 5 gly glycopeptides 1688:1700 arg2 glycopeptides 1688:1700 glycopeptides 1688:1700 glycopeptides 1688:1700 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 5 gly glycopeptides 1688:1700 arg2 They 1666:1669 They 1666:1669 They 1666:1669 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 4 6 theme cartilage 884:892 arg1 proteoglycan 894:905 bovine cartilage proteoglycan 877:905 bovine cartilage proteoglycan 877:905 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 7 7 theme overall 1511:1517 arg1 structure 1519:1527 the following overall structure 1497:1527 the following overall structure 1497:1527 The N-glycosidic glycans have the following overall structure: (Formula: see text). 3813552 9 8 theme NeuAc 1890:1894 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 8 theme NeuAc 1890:1894 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 6 9 theme biantennary 1337:1347 arg1 chains 1282:1287 The N-glycosidic carbohydrate chains 1252:1287 The N-glycosidic carbohydrate chains 1252:1287 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 9 theme biantennary 1337:1347 arg1 glycans 1349:1355 all biantennary glycans 1333:1355 all biantennary glycans containing NeuAc and Fuc 1333:1380 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 1 10 theme chondroitin 151:161 arg1 proteoglycan 171:182 A large Mr chondroitin sulfate proteoglycan 140:182 A large Mr chondroitin sulfate proteoglycan 140:182 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3813552 9 11 theme 2----3 1784:1789 arg1 beta 1795:1798 NeuAc alpha(2----3)Gal beta(1----3) 1772:1806 NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol 1772:1815 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 4 12 contain possessed 779:787 arg1 core 744:747 the isolated proteoglycan core 718:747 the isolated proteoglycan core 718:747 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 4 12 contain possessed 779:787 arg2 epitopes 789:796 epitopes 789:796 epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera 789:983 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 4 12 contain possessed 779:787 arg1 free 753:756 free 753:756 free 753:756 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 10 13 theme isolated 2062:2069 arg1 proteoglycan 2071:2082 the isolated proteoglycan 2058:2082 the isolated proteoglycan 2058:2082 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 3 14 theme heparan 609:615 arg1 proteoglycan 625:636 a residual heparan sulfate proteoglycan 598:636 a residual heparan sulfate proteoglycan 598:636 After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. 3813552 4 15 theme sulfate 968:974 arg1 antisera 976:983 anti-keratan sulfate antisera 955:983 anti-keratan sulfate antisera 955:983 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 11 16 theme latter 2234:2239 arg1 glycans 2241:2247 These latter glycans 2228:2247 These latter glycans 2228:2247 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 16 theme latter 2234:2239 arg1 alditols 2289:2296 oligosaccharide alditols 2273:2296 oligosaccharide alditols 2273:2296 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 9 17 theme NeuAc 1772:1776 arg1 beta 1795:1798 NeuAc alpha(2----3)Gal beta(1----3) 1772:1806 NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol 1772:1815 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 18 theme beta 1915:1918 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 18 theme beta 1915:1918 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 10 19 theme O-glycosidic 2016:2027 arg1 chains 2042:2047 the O-glycosidic carbohydrate chains 2012:2047 the O-glycosidic carbohydrate chains bound to the isolated proteoglycan 2012:2082 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 6 20 theme NeuAc----Gal 1409:1420 arg1 linkage 1422:1428 the NeuAc----Gal linkage 1405:1428 the NeuAc----Gal linkage 1405:1428 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 5 21 theme primary 1139:1145 arg1 structure 1147:1155 their primary structure 1133:1155 their primary structure 1133:1155 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 11 22 theme Gal 2487:2489 arg1 1----4 2496:2501 1----4 2496:2501 1----4 2496:2501 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 22 theme Gal 2487:2489 arg1 beta 2491:2494 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta 2407:2494 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 9 23 theme 1----3 1920:1925 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 23 theme 1----3 1920:1925 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 0 24 theme aorta 133:137 arg1 media 114:118 the media 110:118 the media of the human aorta 110:137 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 5 25 theme Sephadex 1099:1106 arg1 chromatography 1113:1126 Sephadex G-50 chromatography 1099:1126 Sephadex G-50 chromatography 1099:1126 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 9 26 theme [NeuAc 1927:1932 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 26 theme [NeuAc 1927:1932 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 4 27 theme protein 766:772 arg1 core 744:747 the isolated proteoglycan core 718:747 the isolated proteoglycan core 718:747 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 4 27 theme protein 766:772 arg1 free 753:756 free 753:756 free 753:756 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 3 28 theme chromatography 664:677 arg1 step 679:682 a third gel filtration chromatography step 641:682 a third gel filtration chromatography step 641:682 After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. 3813552 9 29 theme beta 1795:1798 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 29 theme beta 1795:1798 arg1 GalNAc-ol 1807:1815 NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol 1772:1815 NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol 1772:1815 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 11 30 theme beta 2441:2444 arg1 1----4 2496:2501 1----4 2496:2501 1----4 2496:2501 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 30 theme beta 2441:2444 arg1 beta 2491:2494 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta 2407:2494 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 4 31 theme proteoglycan 731:742 arg1 core 744:747 the isolated proteoglycan core 718:747 the isolated proteoglycan core 718:747 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 4 31 theme proteoglycan 731:742 arg1 free 753:756 free 753:756 free 753:756 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 11 32 theme 1----3 2464:2469 arg1 1----4 2496:2501 1----4 2496:2501 1----4 2496:2501 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 32 theme 1----3 2464:2469 arg1 beta 2491:2494 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta 2407:2494 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 5 33 theme NMR 1185:1187 arg1 spectroscopy 1189:1200 500-MHz1H NMR spectroscopy 1175:1200 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis 1175:1249 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 3 34 theme gel 649:651 arg1 chromatography 664:677 a third gel filtration chromatography 641:677 a third gel filtration chromatography step 641:682 After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. 3813552 11 35 theme C-6 2401:2403 arg1 Xyl-ol 2503:2508 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 10 36 theme link 2108:2111 arg1 regions 2113:2119 the hexasaccharide link regions 2089:2119 the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule 2089:2225 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 10 36 theme link 2108:2111 arg1 remainder 1999:2007 The remainder 1995:2007 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan 1995:2082 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 5 37 with combination 1205:1215 arg1 analysis 1242:1249 compositional sugar analysis 1222:1249 compositional sugar analysis 1222:1249 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 0 38 theme chondroitin 63:73 arg1 proteoglycan 83:94 a chondroitin sulfate proteoglycan 61:94 a chondroitin sulfate proteoglycan isolated from the media of the human aorta 61:137 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 1 39 theme filtration 344:353 arg1 chromatography 355:368 gel filtration chromatography 340:368 gel filtration chromatography 340:368 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3813552 1 40 theme large 142:146 arg1 proteoglycan 171:182 A large Mr chondroitin sulfate proteoglycan 140:182 A large Mr chondroitin sulfate proteoglycan 140:182 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3813552 8 41 theme O-glycosidic 1571:1582 arg1 chains 1597:1602 the O-glycosidic carbohydrate chains 1567:1602 the O-glycosidic carbohydrate chains bound to the protein core 1567:1628 The majority of the O-glycosidic carbohydrate chains bound to the protein core were found to be of the mucin type. 3813552 9 42 theme beta 1951:1954 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 42 theme beta 1951:1954 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 0 43 theme proteoglycan 83:94 arg1 N- 18:19 N- 18:19 N- 18:19 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 0 43 theme proteoglycan 83:94 arg1 chains 51:56 O-glycosidic carbohydrate chains 25:56 O-glycosidic carbohydrate chains 25:56 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 5 44 theme core 1028:1031 arg1 beta-elimination 996:1011 beta-elimination 996:1011 beta-elimination of the protein core 996:1031 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 6 45 contain containing 1357:1366 arg2 Fuc 1378:1380 Fuc 1378:1380 Fuc 1378:1380 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 45 contain containing 1357:1366 arg2 NeuAc 1368:1372 NeuAc 1368:1372 NeuAc 1368:1372 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 45 contain containing 1357:1366 arg1 glycans 1349:1355 all biantennary glycans 1333:1355 all biantennary glycans containing NeuAc and Fuc 1333:1380 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 45 contain containing 1357:1366 arg1 chains 1282:1287 The N-glycosidic carbohydrate chains 1252:1287 The N-glycosidic carbohydrate chains 1252:1287 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 9 46 theme [NeuAc 1818:1823 arg1 alpha 1861:1865 2----3)Gal beta(1----3)[NeuAc alpha(2----6) 1831:1873 2----3)Gal beta(1----3)[NeuAc alpha(2----6) 1831:1873 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 46 theme [NeuAc 1818:1823 arg1 alpha 1825:1829 [NeuAc alpha 1818:1829 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 8 47 theme chains 1597:1602 arg1 majority 1555:1562 The majority 1551:1562 The majority of the O-glycosidic carbohydrate chains bound to the protein core 1551:1628 The majority of the O-glycosidic carbohydrate chains bound to the protein core were found to be of the mucin type. 3813552 10 48 theme chondroitin 2128:2138 arg1 chains 2148:2153 the chondroitin sulfate chains 2124:2153 the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule 2124:2225 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 2 49 theme proteoglycan 415:426 arg1 Removal 371:377 Removal 371:377 Removal of a contaminating dermatan sulfate proteoglycan 371:426 Removal of a contaminating dermatan sulfate proteoglycan was accomplished by reduction, alkylation and rechromatography on the gel filtration column. 3813552 9 50 theme beta 1842:1845 arg1 alpha 1861:1865 2----3)Gal beta(1----3)[NeuAc alpha(2----6) 1831:1873 2----3)Gal beta(1----3)[NeuAc alpha(2----6) 1831:1873 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 50 theme beta 1842:1845 arg1 alpha 1825:1829 [NeuAc alpha 1818:1829 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 11 51 theme 1----3 2480:2485 arg1 1----4 2496:2501 1----4 2496:2501 1----4 2496:2501 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 51 theme 1----3 2480:2485 arg1 beta 2491:2494 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta 2407:2494 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 9 52 theme GlcNAc 1963:1968 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 52 theme GlcNAc 1963:1968 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 2 53 theme dermatan 398:405 arg1 proteoglycan 415:426 a contaminating dermatan sulfate proteoglycan 382:426 a contaminating dermatan sulfate proteoglycan 382:426 Removal of a contaminating dermatan sulfate proteoglycan was accomplished by reduction, alkylation and rechromatography on the gel filtration column. 3813552 7 54 contain have 1492:1495 arg1 glycans 1484:1490 The N-glycosidic glycans 1467:1490 The N-glycosidic glycans 1467:1490 The N-glycosidic glycans have the following overall structure: (Formula: see text). 3813552 7 54 contain have 1492:1495 arg2 structure 1519:1527 the following overall structure 1497:1527 the following overall structure 1497:1527 The N-glycosidic glycans have the following overall structure: (Formula: see text). 3813552 8 55 theme protein 1617:1623 arg1 core 1625:1628 the protein core 1613:1628 the protein core 1613:1628 The majority of the O-glycosidic carbohydrate chains bound to the protein core were found to be of the mucin type. 3813552 1 56 theme density-gradient 274:289 arg1 centrifugation 291:304 density-gradient centrifugation 274:304 density-gradient centrifugation 274:304 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3813552 2 57 theme filtration 502:511 arg1 column 513:518 the gel filtration column 494:518 the gel filtration column 494:518 Removal of a contaminating dermatan sulfate proteoglycan was accomplished by reduction, alkylation and rechromatography on the gel filtration column. 3813552 10 58 theme carbohydrate 2029:2040 arg1 chains 2042:2047 the O-glycosidic carbohydrate chains 2012:2047 the O-glycosidic carbohydrate chains bound to the isolated proteoglycan 2012:2082 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 4 59 theme binding 859:865 arg1 region 867:872 the hyaluronic acid binding region 839:872 the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera 839:983 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 6 60 from microheterogeneity 1383:1400 arg1 linkage 1422:1428 the NeuAc----Gal linkage 1405:1428 the NeuAc----Gal linkage 1405:1428 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 9 61 theme 1----3 1847:1852 arg1 alpha 1861:1865 2----3)Gal beta(1----3)[NeuAc alpha(2----6) 1831:1873 2----3)Gal beta(1----3)[NeuAc alpha(2----6) 1831:1873 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 61 theme 1----3 1847:1852 arg1 alpha 1825:1829 [NeuAc alpha 1818:1829 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 11 62 theme following 2307:2315 arg1 structure 2317:2325 the following structure 2303:2325 the following structure 2303:2325 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 5 63 from spectroscopy 1189:1200 arg1 combination 1205:1215 combination 1205:1215 combination with compositional sugar analysis 1205:1249 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 5 64 theme sugar 1236:1240 arg1 analysis 1242:1249 compositional sugar analysis 1222:1249 compositional sugar analysis 1222:1249 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 9 65 theme [NeuAc 1854:1859 arg1 alpha 1861:1865 2----3)Gal beta(1----3)[NeuAc alpha(2----6) 1831:1873 2----3)Gal beta(1----3)[NeuAc alpha(2----6) 1831:1873 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 65 theme [NeuAc 1854:1859 arg1 alpha 1825:1829 [NeuAc alpha 1818:1829 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 11 66 theme containing 2359:2368 arg1 sulfate 2370:2376 containing sulfate 2359:2376 containing sulfate 2359:2376 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 5 67 theme low 1048:1050 arg1 oligosaccharides 1055:1070 the liberated low Mr oligosaccharides 1034:1070 the liberated low Mr oligosaccharides 1034:1070 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 8 68 theme mucin 1654:1658 arg1 type 1660:1663 the mucin type 1650:1663 the mucin type 1650:1663 The majority of the O-glycosidic carbohydrate chains bound to the protein core were found to be of the mucin type. 3813552 4 69 theme hyaluronic 843:852 arg1 region 867:872 the hyaluronic acid binding region 839:872 the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera 839:983 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 1 70 theme human 216:220 arg1 aorta 222:226 human aorta 216:226 human aorta 216:226 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3813552 2 71 from reduction 448:456 arg1 column 513:518 the gel filtration column 494:518 the gel filtration column 494:518 Removal of a contaminating dermatan sulfate proteoglycan was accomplished by reduction, alkylation and rechromatography on the gel filtration column. 3813552 11 72 theme oligosaccharide 2273:2287 arg1 glycans 2241:2247 These latter glycans 2228:2247 These latter glycans 2228:2247 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 72 theme oligosaccharide 2273:2287 arg1 alditols 2289:2296 oligosaccharide alditols 2273:2296 oligosaccharide alditols 2273:2296 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 5 73 theme compositional 1222:1234 arg1 analysis 1242:1249 compositional sugar analysis 1222:1249 compositional sugar analysis 1222:1249 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 9 74 dep structures 1760:1769 arg1 GalNAc-ol 1875:1883 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 74 dep structures 1760:1769 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 74 dep structures 1760:1769 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 74 dep structures 1760:1769 arg1 GalNAc-ol 1807:1815 NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol 1772:1815 NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol 1772:1815 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 3 75 theme ABC 542:544 arg1 treatment 546:554 chondroitinase ABC treatment 527:554 chondroitinase ABC treatment 527:554 After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. 3813552 9 76 theme oligosaccharide 1706:1720 arg1 alditols 1722:1729 oligosaccharide alditols 1706:1729 oligosaccharide alditols 1706:1729 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 76 theme oligosaccharide 1706:1720 arg1 They 1666:1669 They 1666:1669 They 1666:1669 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 11 77 theme beta 2475:2478 arg1 1----4 2496:2501 1----4 2496:2501 1----4 2496:2501 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 77 theme beta 2475:2478 arg1 beta 2491:2494 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta 2407:2494 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 6 78 gly glycopeptides 1313:1325 arg2 chains 1282:1287 The N-glycosidic carbohydrate chains 1252:1287 The N-glycosidic carbohydrate chains 1252:1287 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 78 gly glycopeptides 1313:1325 arg2 glycopeptides 1313:1325 glycopeptides 1313:1325 glycopeptides 1313:1325 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 11 79 theme sulfate 2370:2376 arg1 free 2340:2343 free 2340:2343 free 2340:2343 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 6 80 theme N-glycosidic 1256:1267 arg1 chains 1282:1287 The N-glycosidic carbohydrate chains 1252:1287 The N-glycosidic carbohydrate chains 1252:1287 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 80 theme N-glycosidic 1256:1267 arg1 glycans 1349:1355 all biantennary glycans 1333:1355 all biantennary glycans containing NeuAc and Fuc 1333:1380 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 80 theme N-glycosidic 1256:1267 arg1 glycopeptides 1313:1325 glycopeptides 1313:1325 glycopeptides 1313:1325 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 10 81 theme chains 2042:2047 arg1 regions 2113:2119 the hexasaccharide link regions 2089:2119 the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule 2089:2225 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 10 81 theme chains 2042:2047 arg1 remainder 1999:2007 The remainder 1995:2007 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan 1995:2082 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 3 82 theme proteoglycan 561:572 arg1 core 574:577 the proteoglycan core 557:577 the proteoglycan core 557:577 After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. 3813552 1 83 theme Mr 148:149 arg1 proteoglycan 171:182 A large Mr chondroitin sulfate proteoglycan 140:182 A large Mr chondroitin sulfate proteoglycan 140:182 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3813552 0 84 theme carbohydrate 38:49 arg1 chains 51:56 O-glycosidic carbohydrate chains 25:56 O-glycosidic carbohydrate chains 25:56 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 4 85 theme bovine 877:882 arg1 proteoglycan 894:905 bovine cartilage proteoglycan 877:905 bovine cartilage proteoglycan 877:905 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 9 86 theme alpha- 1896:1901 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 86 theme alpha- 1896:1901 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 7 87 dep see 1540:1542 arg1 Formula 1531:1537 Formula 1531:1537 Formula 1531:1537 The N-glycosidic glycans have the following overall structure: (Formula: see text). 3813552 11 88 theme Gal 2471:2473 arg1 1----4 2496:2501 1----4 2496:2501 1----4 2496:2501 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 88 theme Gal 2471:2473 arg1 beta 2491:2494 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta 2407:2494 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 6 89 theme branches 1457:1464 arg1 one 1446:1448 one 1446:1448 one 1446:1448 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 89 theme branches 1457:1464 arg1 branches 1457:1464 the branches 1453:1464 the branches 1453:1464 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 3 90 theme residual 600:607 arg1 proteoglycan 625:636 a residual heparan sulfate proteoglycan 598:636 a residual heparan sulfate proteoglycan 598:636 After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. 3813552 1 91 theme sulfate 163:169 arg1 proteoglycan 171:182 A large Mr chondroitin sulfate proteoglycan 140:182 A large Mr chondroitin sulfate proteoglycan 140:182 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3813552 8 92 theme carbohydrate 1584:1595 arg1 chains 1597:1602 the O-glycosidic carbohydrate chains 1567:1602 the O-glycosidic carbohydrate chains bound to the protein core 1567:1628 The majority of the O-glycosidic carbohydrate chains bound to the protein core were found to be of the mucin type. 3813552 4 93 theme proteoglycan 894:905 arg1 region 867:872 the hyaluronic acid binding region 839:872 the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera 839:983 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 7 94 theme following 1501:1509 arg1 structure 1519:1527 the following overall structure 1497:1527 the following overall structure 1497:1527 The N-glycosidic glycans have the following overall structure: (Formula: see text). 3813552 9 95 theme 2----3 1903:1908 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 95 theme 2----3 1903:1908 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 4 96 theme anti-keratan 955:966 arg1 antisera 976:983 anti-keratan sulfate antisera 955:983 anti-keratan sulfate antisera 955:983 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 11 97 theme 1----3 2427:2432 arg1 beta 2441:2444 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4) 2407:2452 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 9 98 theme Gal 1911:1913 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 98 theme Gal 1911:1913 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 99 dep glycopeptides 1688:1700 arg1 possessed 1736:1744 possessed 1736:1744 possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1736:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 0 100 theme human 127:131 arg1 aorta 133:137 the human aorta 123:137 the human aorta 123:137 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 9 101 theme following 1750:1758 arg1 GalNAc-ol 1875:1883 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 101 theme following 1750:1758 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 101 theme following 1750:1758 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 101 theme following 1750:1758 arg1 GalNAc-ol 1807:1815 NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol 1772:1815 NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol 1772:1815 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 102 theme alpha 1778:1782 arg1 beta 1795:1798 NeuAc alpha(2----3)Gal beta(1----3) 1772:1806 NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol 1772:1815 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 11 103 theme beta 2422:2425 arg1 beta 2441:2444 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4) 2407:2452 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 7 104 theme N-glycosidic 1471:1482 arg1 glycans 1484:1490 The N-glycosidic glycans 1467:1490 The N-glycosidic glycans 1467:1490 The N-glycosidic glycans have the following overall structure: (Formula: see text). 3813552 10 105 theme hexasaccharide 2093:2106 arg1 regions 2113:2119 the hexasaccharide link regions 2089:2119 the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule 2089:2225 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 10 105 theme hexasaccharide 2093:2106 arg1 remainder 1999:2007 The remainder 1995:2007 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan 1995:2082 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 3 106 theme sulfate 617:623 arg1 proteoglycan 625:636 a residual heparan sulfate proteoglycan 598:636 a residual heparan sulfate proteoglycan 598:636 After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. 3813552 9 107 theme structures 1760:1769 arg1 GalNAc-ol 1984:1992 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 11 108 theme free 2340:2343 arg1 GalNAc 2333:2338 GalNAc 2333:2338 GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2333:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 5 109 theme G-50 1108:1111 arg1 chromatography 1113:1126 Sephadex G-50 chromatography 1099:1126 Sephadex G-50 chromatography 1099:1126 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 3 110 theme filtration 653:662 arg1 chromatography 664:677 a third gel filtration chromatography 641:677 a third gel filtration chromatography step 641:682 After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. 3813552 10 111 theme chains 2148:2153 arg1 regions 2113:2119 the hexasaccharide link regions 2089:2119 the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule 2089:2225 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 10 111 theme chains 2148:2153 arg1 remainder 1999:2007 The remainder 1995:2007 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan 1995:2082 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 9 112 theme Gal 1791:1793 arg1 beta 1795:1798 NeuAc alpha(2----3)Gal beta(1----3) 1772:1806 NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol 1772:1815 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 11 113 theme GalNAc 2434:2439 arg1 beta 2441:2444 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4) 2407:2452 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 9 114 theme alpha 1934:1938 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 114 theme alpha 1934:1938 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 4 115 theme link 761:764 arg1 protein 766:772 link protein 761:772 link protein 761:772 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 3 116 theme third 643:647 arg1 chromatography 664:677 a third gel filtration chromatography 641:677 a third gel filtration chromatography step 641:682 After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. 3813552 2 117 from alkylation 459:468 arg1 column 513:518 the gel filtration column 494:518 the gel filtration column 494:518 Removal of a contaminating dermatan sulfate proteoglycan was accomplished by reduction, alkylation and rechromatography on the gel filtration column. 3813552 9 118 theme 2----3 1940:1945 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 118 theme 2----3 1940:1945 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 4 119 theme isolated 722:729 arg1 core 744:747 the isolated proteoglycan core 718:747 the isolated proteoglycan core 718:747 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 4 119 theme isolated 722:729 arg1 free 753:756 free 753:756 free 753:756 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 0 120 theme sulfate 75:81 arg1 proteoglycan 83:94 a chondroitin sulfate proteoglycan 61:94 a chondroitin sulfate proteoglycan isolated from the media of the human aorta 61:137 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 1 121 theme gel 340:342 arg1 chromatography 355:368 gel filtration chromatography 340:368 gel filtration chromatography 340:368 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3813552 6 122 located detected 1434:1441 arg1 branches 1457:1464 the branches 1453:1464 the branches 1453:1464 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 122 located detected 1434:1441 arg1 one 1446:1448 one 1446:1448 one 1446:1448 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 6 122 located detected 1434:1441 arg2 microheterogeneity 1383:1400 microheterogeneity 1383:1400 microheterogeneity in the NeuAc----Gal linkage 1383:1428 The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. 3813552 2 123 from rechromatography 474:489 arg1 column 513:518 the gel filtration column 494:518 the gel filtration column 494:518 Removal of a contaminating dermatan sulfate proteoglycan was accomplished by reduction, alkylation and rechromatography on the gel filtration column. 3813552 9 124 theme Gal 1947:1949 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 124 theme Gal 1947:1949 arg1 beta 1970:1973 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6) 1890:1981 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 5 125 theme protein 1020:1026 arg1 core 1028:1031 the protein core 1016:1031 the protein core 1016:1031 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 11 126 theme delta 2407:2411 arg1 beta 2441:2444 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4) 2407:2452 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 10 127 theme sulfate 2140:2146 arg1 chains 2148:2153 the chondroitin sulfate chains 2124:2153 the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule 2124:2225 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 9 128 theme alpha 1825:1829 arg1 structures 1760:1769 the following structures 1746:1769 the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol 1746:1992 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 128 theme alpha 1825:1829 arg1 GalNAc-ol 1875:1883 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 10 129 theme ABC 2190:2192 arg1 treatment 2194:2202 chondroitinase ABC treatment 2175:2202 chondroitinase ABC treatment of the native molecule 2175:2225 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 2 130 theme sulfate 407:413 arg1 proteoglycan 415:426 a contaminating dermatan sulfate proteoglycan 382:426 a contaminating dermatan sulfate proteoglycan 382:426 Removal of a contaminating dermatan sulfate proteoglycan was accomplished by reduction, alkylation and rechromatography on the gel filtration column. 3813552 5 131 theme 500-MHz1H 1175:1183 arg1 spectroscopy 1189:1200 500-MHz1H NMR spectroscopy 1175:1200 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis 1175:1249 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 11 132 theme 4,5GlcUA 2413:2420 arg1 beta 2441:2444 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4) 2407:2452 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 2 133 theme contaminating 384:396 arg1 proteoglycan 415:426 a contaminating dermatan sulfate proteoglycan 382:426 a contaminating dermatan sulfate proteoglycan 382:426 Removal of a contaminating dermatan sulfate proteoglycan was accomplished by reduction, alkylation and rechromatography on the gel filtration column. 3813552 0 134 theme N- 18:19 arg1 structures 4:13 The structures 0:13 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 0:138 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 9 135 theme Gal 1838:1840 arg1 alpha 1861:1865 2----3)Gal beta(1----3)[NeuAc alpha(2----6) 1831:1873 2----3)Gal beta(1----3)[NeuAc alpha(2----6) 1831:1873 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 9 135 theme Gal 1838:1840 arg1 alpha 1825:1829 [NeuAc alpha 1818:1829 [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol 1818:1883 They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. 3813552 0 136 theme O-glycosidic 25:36 arg1 chains 51:56 O-glycosidic carbohydrate chains 25:56 O-glycosidic carbohydrate chains 25:56 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 2 137 theme gel 498:500 arg1 column 513:518 the gel filtration column 494:518 the gel filtration column 494:518 Removal of a contaminating dermatan sulfate proteoglycan was accomplished by reduction, alkylation and rechromatography on the gel filtration column. 3813552 4 138 theme acid 854:857 arg1 region 867:872 the hyaluronic acid binding region 839:872 the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera 839:983 As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. 3813552 0 139 theme chains 51:56 arg1 structures 4:13 The structures 0:13 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 0:138 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 1 140 theme ion-exchange 307:318 arg1 chromatography 320:333 ion-exchange chromatography 307:333 ion-exchange chromatography 307:333 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3813552 11 141 theme beta 2491:2494 arg1 Xyl-ol 2503:2508 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 3 142 theme chondroitinase 527:540 arg1 ABC 542:544 chondroitinase ABC 527:544 chondroitinase ABC treatment 527:554 After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. 3813552 5 143 theme liberated 1038:1046 arg1 oligosaccharides 1055:1070 the liberated low Mr oligosaccharides 1034:1070 the liberated low Mr oligosaccharides 1034:1070 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 10 144 theme molecule 2218:2225 arg1 treatment 2194:2202 chondroitinase ABC treatment 2175:2202 chondroitinase ABC treatment of the native molecule 2175:2225 The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. 3813552 11 145 theme beta 2459:2462 arg1 1----4 2496:2501 1----4 2496:2501 1----4 2496:2501 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 145 theme beta 2459:2462 arg1 beta 2491:2494 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta 2407:2494 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 146 theme sulfate 2348:2354 arg1 free 2340:2343 free 2340:2343 free 2340:2343 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 5 147 theme Mr 1052:1053 arg1 oligosaccharides 1055:1070 the liberated low Mr oligosaccharides 1034:1070 the liberated low Mr oligosaccharides 1034:1070 Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. 3813552 0 148 attach isolated 96:103 arg1 media 114:118 the media 110:118 the media of the human aorta 110:137 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 0 148 attach isolated 96:103 arg2 proteoglycan 83:94 a chondroitin sulfate proteoglycan 61:94 a chondroitin sulfate proteoglycan isolated from the media of the human aorta 61:137 The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta. 3813552 11 149 theme GlcUA 2453:2457 arg1 1----4 2496:2501 1----4 2496:2501 1----4 2496:2501 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 11 149 theme GlcUA 2453:2457 arg1 beta 2491:2494 delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta 2407:2494 C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol 2401:2508 These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol. 3813552 1 150 theme aorta 222:226 arg1 media 207:211 the media 203:211 the media of human aorta 203:226 A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. 3335536 0 0 theme present 81:87 arg1 gonadotropin 68:79 human chorionic gonadotropin 52:79 human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women 52:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 1 1 theme mucin-type 335:344 arg1 chains 352:357 approximately four mucin-type sugar chains 316:357 approximately four mucin-type sugar chains in one molecule 316:373 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 1 2 from chains 352:357 arg1 molecule 366:373 one molecule 362:373 one molecule 362:373 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 4 3 theme sugar 907:911 arg1 chains 913:918 the total mucin-type sugar chains 886:918 the total mucin-type sugar chains 886:918 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 4 4 theme mucin-type 896:905 arg1 chains 913:918 the total mucin-type sugar chains 886:918 the total mucin-type sugar chains 886:918 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 4 5 contain containing 822:831 arg1 oligosaccharides 805:820 oligosaccharides 805:820 oligosaccharides containing the tetrasaccharide core 805:856 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 4 5 contain containing 822:831 arg2 core 853:856 the tetrasaccharide core 833:856 the tetrasaccharide core 833:856 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 0 6 theme gonadotropin 68:79 arg1 chains 42:47 the mucin-type sugar chains 21:47 the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women 21:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 1 7 theme sugar 346:350 arg1 chains 352:357 approximately four mucin-type sugar chains 316:357 approximately four mucin-type sugar chains in one molecule 316:373 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 2 8 theme mucin-type 482:491 arg1 chains 499:504 mucin-type sugar chains 482:504 mucin-type sugar chains 482:504 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 2 8 theme mucin-type 482:491 arg1 oligosaccharides 536:551 radioactive oligosaccharides 524:551 radioactive oligosaccharides from a small amount of glycoproteins 524:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 3 9 theme nonsialylated 654:666 arg1 GalNAc 744:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 1 10 theme patients 241:248 arg1 urine 232:236 the urine 228:236 the urine of patients with trophoblastic diseases and of healthy pregnant women 228:306 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 3 11 theme beta 716:719 arg1 GalNAc 744:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 3 12 theme Gal 668:670 arg1 beta 732:735 Gal beta 1----3 728:742 Gal beta 1----3 728:742 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 3 12 theme Gal 668:670 arg1 1----3GalNAc 677:688 Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6 668:726 1----3GalNAc 677:688 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 6 13 theme hCG 1156:1158 arg1 proportion 1126:1135 the proportion 1122:1135 the proportion of choriocarcinoma hCG 1122:1158 The proportion in invasive mole hCG was also increased, but less than the proportion of choriocarcinoma hCG. 3335536 3 14 gly nonsialylated 654:666 arg1 GalNAc 744:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 2 15 theme radioactive 524:534 arg1 chains 499:504 mucin-type sugar chains 482:504 mucin-type sugar chains 482:504 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 2 15 theme radioactive 524:534 arg1 oligosaccharides 536:551 radioactive oligosaccharides 524:551 radioactive oligosaccharides from a small amount of glycoproteins 524:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 3 16 theme 1----4GlcNAc 703:714 arg1 beta 716:719 Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6 668:726 beta 716:719 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 1 17 with patients 241:248 arg1 diseases 269:276 trophoblastic diseases 255:276 trophoblastic diseases 255:276 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 1 18 theme trophoblastic 255:267 arg1 diseases 269:276 trophoblastic diseases 255:276 trophoblastic diseases 255:276 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 2 19 theme small 560:564 arg1 glycoproteins 576:588 glycoproteins 576:588 glycoproteins 576:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 2 19 theme small 560:564 arg1 amount 566:571 a small amount 558:571 a small amount of glycoproteins 558:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 4 20 theme hCG 774:776 arg1 case 759:762 the case 755:762 the case of normal hCG and hydatidiform mole hCG 755:802 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 3 21 gly sialylated 639:648 arg1 GalNAc 744:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 2 22 theme new 451:453 arg1 method 465:470 a new sensitive method 449:470 a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins 449:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 3 23 theme Gal 728:730 arg1 beta 732:735 Gal beta 1----3 728:742 Gal beta 1----3 728:742 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 3 23 theme Gal 728:730 arg1 1----3GalNAc 677:688 Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6 668:726 1----3GalNAc 677:688 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 4 24 theme tetrasaccharide 837:851 arg1 core 853:856 the tetrasaccharide core 833:856 the tetrasaccharide core 833:856 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 4 25 theme normal 767:772 arg1 hCG 774:776 normal hCG 767:776 normal hCG 767:776 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 1 26 theme Human 170:174 arg1 hCGs 201:204 hCGs 201:204 hCGs 201:204 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 1 26 theme Human 170:174 arg1 gonadotropins 186:198 Human chorionic gonadotropins 170:198 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women 170:306 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 6 27 from proportion 1056:1065 arg1 mole 1079:1082 invasive mole hCG 1070:1086 invasive mole hCG 1070:1086 The proportion in invasive mole hCG was also increased, but less than the proportion of choriocarcinoma hCG. 3335536 1 28 theme chorionic 176:184 arg1 hCGs 201:204 hCGs 201:204 hCGs 201:204 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 1 28 theme chorionic 176:184 arg1 gonadotropins 186:198 Human chorionic gonadotropins 170:198 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women 170:306 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 0 29 theme Comparative 0:10 arg1 study 12:16 Comparative study 0:16 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 0:168 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 1 30 contain contain 308:314 arg1 hCGs 201:204 hCGs 201:204 hCGs 201:204 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 1 30 contain contain 308:314 arg1 gonadotropins 186:198 Human chorionic gonadotropins 170:198 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women 170:306 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 1 30 contain contain 308:314 arg2 chains 352:357 approximately four mucin-type sugar chains 316:357 approximately four mucin-type sugar chains in one molecule 316:373 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 3 31 theme sugar 606:610 arg1 chains 612:617 The mucin-type sugar chains 591:617 The mucin-type sugar chains of all hCGs 591:629 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 5 32 theme containing 954:963 arg1 oligosaccharides 965:980 the tetrasaccharide containing oligosaccharides 934:980 the tetrasaccharide containing oligosaccharides 934:980 The ratio of the tetrasaccharide containing oligosaccharides is increased prominently to approximately 60% in choriocarcinoma hCG. 3335536 5 33 theme tetrasaccharide 938:952 arg1 oligosaccharides 965:980 the tetrasaccharide containing oligosaccharides 934:980 the tetrasaccharide containing oligosaccharides 934:980 The ratio of the tetrasaccharide containing oligosaccharides is increased prominently to approximately 60% in choriocarcinoma hCG. 3335536 0 34 theme patients 105:112 arg1 urine 96:100 the urine 92:100 the urine of patients with trophoblastic diseases and healthy pregnant women 92:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 0 35 from present 81:87 arg1 urine 96:100 the urine 92:100 the urine of patients with trophoblastic diseases and healthy pregnant women 92:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 5 36 theme oligosaccharides 965:980 arg1 ratio 925:929 The ratio 921:929 The ratio of the tetrasaccharide containing oligosaccharides 921:980 The ratio of the tetrasaccharide containing oligosaccharides is increased prominently to approximately 60% in choriocarcinoma hCG. 3335536 6 37 theme invasive 1070:1077 arg1 mole 1079:1082 invasive mole hCG 1070:1086 invasive mole hCG 1070:1086 The proportion in invasive mole hCG was also increased, but less than the proportion of choriocarcinoma hCG. 3335536 0 38 theme sugar 36:40 arg1 chains 42:47 the mucin-type sugar chains 21:47 the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women 21:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 1 39 theme healthy 285:291 arg1 women 302:306 healthy pregnant women 285:306 healthy pregnant women 285:306 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 3 40 theme beta 672:675 arg1 beta 732:735 Gal beta 1----3 728:742 Gal beta 1----3 728:742 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 3 40 theme beta 672:675 arg1 1----3GalNAc 677:688 Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6 668:726 1----3GalNAc 677:688 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 5 41 theme choriocarcinoma 1031:1045 arg1 hCG 1047:1049 choriocarcinoma hCG 1031:1049 choriocarcinoma hCG 1031:1049 The ratio of the tetrasaccharide containing oligosaccharides is increased prominently to approximately 60% in choriocarcinoma hCG. 3335536 2 42 theme chains 406:411 arg1 structures 380:389 The structures 376:389 The structures of these sugar chains 376:411 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 0 43 theme mucin-type 25:34 arg1 chains 42:47 the mucin-type sugar chains 21:47 the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women 21:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 1 44 theme pregnant 293:300 arg1 women 302:306 healthy pregnant women 285:306 healthy pregnant women 285:306 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 0 45 theme trophoblastic 119:131 arg1 diseases 133:140 trophoblastic diseases 119:140 trophoblastic diseases 119:140 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 2 46 theme sugar 400:404 arg1 chains 406:411 these sugar chains 394:411 these sugar chains 394:411 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 2 47 theme sensitive 455:463 arg1 method 465:470 a new sensitive method 449:470 a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins 449:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 1 48 theme women 302:306 arg1 patients 241:248 patients 241:248 patients with trophoblastic diseases and of healthy pregnant women 241:306 Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. 3335536 0 49 theme healthy 146:152 arg1 women 163:167 healthy pregnant women 146:167 healthy pregnant women 146:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 2 50 theme sugar 493:497 arg1 chains 499:504 mucin-type sugar chains 482:504 mucin-type sugar chains 482:504 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 2 50 theme sugar 493:497 arg1 oligosaccharides 536:551 radioactive oligosaccharides 524:551 radioactive oligosaccharides from a small amount of glycoproteins 524:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 3 51 theme mucin-type 595:604 arg1 chains 612:617 The mucin-type sugar chains 591:617 The mucin-type sugar chains of all hCGs 591:629 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 4 52 theme chains 913:918 arg1 % 881:881 approximately 10% 865:881 approximately 10% of the total mucin-type sugar chains 865:918 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 4 52 theme chains 913:918 arg1 chains 913:918 the total mucin-type sugar chains 886:918 the total mucin-type sugar chains 886:918 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 6 53 theme choriocarcinoma 1140:1154 arg1 hCG 1156:1158 choriocarcinoma hCG 1140:1158 choriocarcinoma hCG 1140:1158 The proportion in invasive mole hCG was also increased, but less than the proportion of choriocarcinoma hCG. 3335536 0 54 theme chains 42:47 arg1 study 12:16 Comparative study 0:16 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 0:168 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 4 55 theme total 890:894 arg1 chains 913:918 the total mucin-type sugar chains 886:918 the total mucin-type sugar chains 886:918 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 3 56 theme Gal 694:696 arg1 beta 716:719 Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6 668:726 beta 716:719 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 3 57 theme beta 698:701 arg1 beta 716:719 Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6 668:726 beta 716:719 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 4 58 theme mole 795:798 arg1 case 759:762 the case 755:762 the case of normal hCG and hydatidiform mole hCG 755:802 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 2 59 theme glycoproteins 576:588 arg1 glycoproteins 576:588 glycoproteins 576:588 glycoproteins 576:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 2 59 theme glycoproteins 576:588 arg1 amount 566:571 a small amount 558:571 a small amount of glycoproteins 558:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 0 60 from urine 96:100 arg1 present 81:87 present 81:87 present 81:87 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 4 61 theme hydatidiform 782:793 arg1 mole 795:798 hydatidiform mole 782:798 hydatidiform mole 782:798 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 0 62 attach present 81:87 arg1 urine 96:100 the urine 92:100 the urine of patients with trophoblastic diseases and healthy pregnant women 92:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 0 62 attach present 81:87 arg2 gonadotropin 68:79 human chorionic gonadotropin 52:79 human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women 52:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 0 63 theme pregnant 154:161 arg1 women 163:167 healthy pregnant women 146:167 healthy pregnant women 146:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 3 64 theme 1----3GalNAc 677:688 arg1 GalNAc 744:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 3 65 theme sialylated 639:648 arg1 GalNAc 744:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc 639:749 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 3335536 2 66 gly glycoproteins 576:588 arg1 glycoproteins 576:588 glycoproteins 576:588 glycoproteins 576:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 0 67 theme chorionic 58:66 arg1 gonadotropin 68:79 human chorionic gonadotropin 52:79 human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women 52:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 4 68 dep hCG 774:776 arg1 hCG 800:802 hCG 800:802 hCG 800:802 In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. 3335536 0 69 with patients 105:112 arg1 diseases 133:140 trophoblastic diseases 119:140 trophoblastic diseases 119:140 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 0 69 with patients 105:112 arg1 women 163:167 healthy pregnant women 146:167 healthy pregnant women 146:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 2 70 from amount 566:571 arg1 chains 499:504 mucin-type sugar chains 482:504 mucin-type sugar chains 482:504 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 2 70 from amount 566:571 arg1 oligosaccharides 536:551 radioactive oligosaccharides 524:551 radioactive oligosaccharides from a small amount of glycoproteins 524:588 The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin-type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. 3335536 0 71 theme human 52:56 arg1 gonadotropin 68:79 human chorionic gonadotropin 52:79 human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women 52:167 Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. 3335536 3 72 theme hCGs 626:629 arg1 chains 612:617 The mucin-type sugar chains 591:617 The mucin-type sugar chains of all hCGs 591:629 The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 10574203 3 0 theme laser 575:579 arg1 time-of-flight 603:616 matrix-assisted laser desorption ionization time-of-flight 559:616 matrix-assisted laser desorption ionization time-of-flight 559:616 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 0 1 theme glycans 86:92 arg1 characterisation 66:81 characterisation 66:81 characterisation 66:81 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 0 1 theme glycans 86:92 arg1 glycoprotein 49:60 glycoprotein 49:60 glycoprotein 49:60 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 2 2 theme F 362:362 arg1 digestion 364:372 PNGase F digestion 355:372 PNGase F digestion 355:372 Glycans released from the tryptic peptide mixture by PNGase F digestion were then derivatised with 2-aminoacridone. 10574203 0 3 theme liquid 114:119 arg1 chromatography 121:134 high-performance liquid chromatography 97:134 high-performance liquid chromatography 97:134 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 3 4 theme mass 635:638 arg1 analysis 654:661 electrospray mass spectrometric analysis 622:661 electrospray mass spectrometric analysis 622:661 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 0 5 theme high-performance 97:112 arg1 chromatography 121:134 high-performance liquid chromatography 97:134 high-performance liquid chromatography 97:134 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 3 6 theme spectrometric 640:652 arg1 analysis 654:661 electrospray mass spectrometric analysis 622:661 electrospray mass spectrometric analysis 622:661 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 1 7 theme microg 178:183 arg1 Samples 159:165 Samples 159:165 Samples of 5 to 20 microg of human IgG 159:196 Samples of 5 to 20 microg of human IgG were subjected to dithiothreitol treatment to reduce disulphide bridges, followed by tryptic digestion. 10574203 3 8 theme electrospray 622:633 arg1 analysis 654:661 electrospray mass spectrometric analysis 622:661 electrospray mass spectrometric analysis 622:661 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 3 9 theme liquid 492:497 arg1 chromatography 499:512 normal-phase high-performance liquid chromatography 462:512 normal-phase high-performance liquid chromatography 462:512 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 0 10 from quantities 35:44 arg1 release 13:19 Carbohydrate release 0:19 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 0:157 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 2 11 theme tryptic 328:334 arg1 mixture 344:350 the tryptic peptide mixture 324:350 the tryptic peptide mixture 324:350 Glycans released from the tryptic peptide mixture by PNGase F digestion were then derivatised with 2-aminoacridone. 10574203 1 12 theme human 188:192 arg1 IgG 194:196 human IgG 188:196 human IgG 188:196 Samples of 5 to 20 microg of human IgG were subjected to dithiothreitol treatment to reduce disulphide bridges, followed by tryptic digestion. 10574203 0 13 theme Carbohydrate 0:11 arg1 release 13:19 Carbohydrate release 0:19 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 0:157 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 1 14 theme tryptic 283:289 arg1 digestion 291:299 tryptic digestion 283:299 tryptic digestion 283:299 Samples of 5 to 20 microg of human IgG were subjected to dithiothreitol treatment to reduce disulphide bridges, followed by tryptic digestion. 10574203 1 15 dep 20 175:176 arg1 to 172:173 to 172:173 to 172:173 Samples of 5 to 20 microg of human IgG were subjected to dithiothreitol treatment to reduce disulphide bridges, followed by tryptic digestion. 10574203 1 16 theme IgG 194:196 arg1 microg 178:183 5 to 20 microg 170:183 5 to 20 microg of human IgG 170:196 Samples of 5 to 20 microg of human IgG were subjected to dithiothreitol treatment to reduce disulphide bridges, followed by tryptic digestion. 10574203 0 17 theme picomole 26:33 arg1 quantities 35:44 picomole quantities 26:44 picomole quantities of glycoprotein and characterisation of glycans 26:92 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 3 18 theme individual 518:527 arg1 components 529:538 individual components 518:538 individual components 518:538 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 2 19 attach released 310:317 arg2 Glycans 302:308 Glycans 302:308 Glycans released from the tryptic peptide mixture by PNGase F digestion 302:372 Glycans released from the tryptic peptide mixture by PNGase F digestion were then derivatised with 2-aminoacridone. 10574203 2 19 attach released 310:317 arg1 mixture 344:350 the tryptic peptide mixture 324:350 the tryptic peptide mixture 324:350 Glycans released from the tryptic peptide mixture by PNGase F digestion were then derivatised with 2-aminoacridone. 10574203 0 20 theme mass 140:143 arg1 spectrometry 145:156 mass spectrometry 140:156 mass spectrometry 140:156 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 3 21 theme desorption 581:590 arg1 time-of-flight 603:616 matrix-assisted laser desorption ionization time-of-flight 559:616 matrix-assisted laser desorption ionization time-of-flight 559:616 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 3 22 theme normal-phase 462:473 arg1 chromatography 499:512 normal-phase high-performance liquid chromatography 462:512 normal-phase high-performance liquid chromatography 462:512 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 3 23 theme high-performance 475:490 arg1 chromatography 499:512 normal-phase high-performance liquid chromatography 462:512 normal-phase high-performance liquid chromatography 462:512 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 1 24 theme dithiothreitol 216:229 arg1 treatment 231:239 dithiothreitol treatment 216:239 dithiothreitol treatment 216:239 Samples of 5 to 20 microg of human IgG were subjected to dithiothreitol treatment to reduce disulphide bridges, followed by tryptic digestion. 10574203 3 25 theme Labelled 418:425 arg1 oligosaccharides 427:442 Labelled oligosaccharides 418:442 Labelled oligosaccharides 418:442 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 2 26 theme PNGase 355:360 arg1 digestion 364:372 PNGase F digestion 355:372 PNGase F digestion 355:372 Glycans released from the tryptic peptide mixture by PNGase F digestion were then derivatised with 2-aminoacridone. 10574203 0 27 theme glycoprotein 49:60 arg1 quantities 35:44 picomole quantities 26:44 picomole quantities of glycoprotein and characterisation of glycans 26:92 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 3 28 theme matrix-assisted 559:573 arg1 time-of-flight 603:616 matrix-assisted laser desorption ionization time-of-flight 559:616 matrix-assisted laser desorption ionization time-of-flight 559:616 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 2 29 theme peptide 336:342 arg1 mixture 344:350 the tryptic peptide mixture 324:350 the tryptic peptide mixture 324:350 Glycans released from the tryptic peptide mixture by PNGase F digestion were then derivatised with 2-aminoacridone. 10574203 0 30 gly glycoprotein 49:60 arg1 glycoprotein 49:60 glycoprotein 49:60 glycoprotein 49:60 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 3 31 theme ionization 592:601 arg1 time-of-flight 603:616 matrix-assisted laser desorption ionization time-of-flight 559:616 matrix-assisted laser desorption ionization time-of-flight 559:616 Labelled oligosaccharides were separated by normal-phase high-performance liquid chromatography and individual components were collected for matrix-assisted laser desorption ionization time-of-flight and electrospray mass spectrometric analysis. 10574203 0 32 theme characterisation 66:81 arg1 quantities 35:44 picomole quantities 26:44 picomole quantities of glycoprotein and characterisation of glycans 26:92 Carbohydrate release from picomole quantities of glycoprotein and characterisation of glycans by high-performance liquid chromatography and mass spectrometry. 10574203 1 33 theme disulphide 251:260 arg1 bridges 262:268 disulphide bridges 251:268 disulphide bridges 251:268 Samples of 5 to 20 microg of human IgG were subjected to dithiothreitol treatment to reduce disulphide bridges, followed by tryptic digestion. 2124546 0 0 theme ovary 95:99 arg1 cells 101:105 Chinese hamster ovary cells 79:105 Chinese hamster ovary cells 79:105 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 1 1 theme hamster 360:366 arg1 cells 374:378 Chinese hamster ovary cells 352:378 Chinese hamster ovary cells 352:378 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 2 2 theme erythropoietin 657:670 arg1 chains 609:614 the enzymatically released N-linked carbohydrate chains 560:614 the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin 560:670 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 2 3 theme chains 609:614 arg1 analysis 517:524 Structural analysis 506:524 Structural analysis 506:524 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 1 4 theme sialic 169:174 arg1 acids 176:180 sialic acids 169:180 sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, 169:379 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 5 theme plasminogen 271:281 arg1 activator 283:291 human chimeric plasminogen activator 256:291 human chimeric plasminogen activator 256:291 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 0 6 theme hamster 87:93 arg1 cells 101:105 Chinese hamster ovary cells 79:105 Chinese hamster ovary cells 79:105 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 1 7 theme ovary 368:372 arg1 cells 374:378 Chinese hamster ovary cells 352:378 Chinese hamster ovary cells 352:378 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 8 theme acid 481:484 arg1 presence 420:427 the presence 416:427 the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3 416:503 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 9 theme acids 176:180 arg1 analysis 157:164 HPLC analysis 152:164 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, 152:379 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 10 theme activator 283:291 arg1 variants 208:215 recombinant variants 196:215 recombinant variants 196:215 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 11 from presence 420:427 arg1 ratio 491:495 a ratio 489:495 a ratio of 97:3 489:503 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 2 12 theme N-glycolylneuraminic 702:721 arg1 acid 723:726 alpha 2-3 linked N-glycolylneuraminic acid 685:726 alpha 2-3 linked N-glycolylneuraminic acid 685:726 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 2 13 theme activator 640:648 arg1 chains 609:614 the enzymatically released N-linked carbohydrate chains 560:614 the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin 560:670 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 2 14 theme linked 695:700 arg1 acid 723:726 alpha 2-3 linked N-glycolylneuraminic acid 685:726 alpha 2-3 linked N-glycolylneuraminic acid 685:726 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 1 15 theme human 294:298 arg1 erythropoietin 300:313 human erythropoietin 294:313 human erythropoietin 294:313 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 2 16 theme alpha 685:689 arg1 acid 723:726 alpha 2-3 linked N-glycolylneuraminic acid 685:726 alpha 2-3 linked N-glycolylneuraminic acid 685:726 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 2 17 theme 2-3 691:693 arg1 acid 723:726 alpha 2-3 linked N-glycolylneuraminic acid 685:726 alpha 2-3 linked N-glycolylneuraminic acid 685:726 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 2 18 theme Structural 506:515 arg1 analysis 517:524 Structural analysis 506:524 Structural analysis 506:524 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 2 19 theme different 741:749 arg1 structures 786:795 different N-acetyllactosamine type antennary structures 741:795 different N-acetyllactosamine type antennary structures 741:795 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 0 20 theme carbohydrate 11:22 arg1 chains 24:29 Sialylated carbohydrate chains 0:29 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells 0:105 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 1 21 theme 97:3 500:503 arg1 ratio 491:495 a ratio 489:495 a ratio of 97:3 489:503 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 2 22 link N-linked 587:594 arg1 chains 609:614 the enzymatically released N-linked carbohydrate chains 560:614 the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin 560:670 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 1 23 theme recombinant 196:206 arg1 variants 208:215 recombinant variants 196:215 recombinant variants 196:215 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 0 24 theme Sialylated 0:9 arg1 chains 24:29 Sialylated carbohydrate chains 0:29 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells 0:105 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 1 25 theme erythropoietin 300:313 arg1 variants 208:215 recombinant variants 196:215 recombinant variants 196:215 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 26 attach presence 420:427 arg2 acid 481:484 N-glycolylneuraminic acid 460:484 N-glycolylneuraminic acid 460:484 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 26 attach presence 420:427 arg2 acid 451:454 N-acetylneuraminic acid 432:454 N-acetylneuraminic acid 432:454 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 26 attach presence 420:427 arg1 ratio 491:495 a ratio 489:495 a ratio of 97:3 489:503 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 0 27 theme acid 146:149 arg1 traces 115:120 traces 115:120 traces of N-glycolylneuraminic acid 115:149 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 0 28 theme N-glycolylneuraminic 125:144 arg1 acid 146:149 N-glycolylneuraminic acid 125:149 N-glycolylneuraminic acid 125:149 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 2 29 theme chimeric 619:626 arg1 activator 640:648 chimeric plasminogen activator 619:648 chimeric plasminogen activator 619:648 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 1 30 theme human 220:224 arg1 activator 245:253 human tissue plasminogen activator 220:253 human tissue plasminogen activator 220:253 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 0 31 theme human 46:50 arg1 glycoproteins 52:64 recombinant human glycoproteins 34:64 recombinant human glycoproteins expressed in Chinese hamster ovary cells 34:105 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 1 32 theme human 320:324 arg1 follitropin 326:336 human follitropin 320:336 human follitropin 320:336 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 2 33 theme released 578:585 arg1 chains 609:614 the enzymatically released N-linked carbohydrate chains 560:614 the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin 560:670 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 1 34 attach released 182:189 arg2 acids 176:180 sialic acids 169:180 sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, 169:379 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 34 attach released 182:189 arg1 variants 208:215 recombinant variants 196:215 recombinant variants 196:215 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 35 theme tissue 226:231 arg1 activator 245:253 human tissue plasminogen activator 220:253 human tissue plasminogen activator 220:253 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 0 36 theme recombinant 34:44 arg1 glycoproteins 52:64 recombinant human glycoproteins 34:64 recombinant human glycoproteins expressed in Chinese hamster ovary cells 34:105 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 1 37 theme follitropin 326:336 arg1 variants 208:215 recombinant variants 196:215 recombinant variants 196:215 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 38 theme plasminogen 233:243 arg1 activator 245:253 human tissue plasminogen activator 220:253 human tissue plasminogen activator 220:253 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 2 39 theme MHz1H-NMR 533:541 arg1 spectroscopy 543:554 500 MHz1H-NMR spectroscopy 529:554 500 MHz1H-NMR spectroscopy 529:554 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 2 40 theme plasminogen 628:638 arg1 activator 640:648 chimeric plasminogen activator 619:648 chimeric plasminogen activator 619:648 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 2 41 theme antennary 776:784 arg1 structures 786:795 different N-acetyllactosamine type antennary structures 741:795 different N-acetyllactosamine type antennary structures 741:795 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 0 42 theme glycoproteins 52:64 arg1 chains 24:29 Sialylated carbohydrate chains 0:29 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells 0:105 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 2 43 theme carbohydrate 596:607 arg1 chains 609:614 the enzymatically released N-linked carbohydrate chains 560:614 the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin 560:670 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 1 44 theme N-acetylneuraminic 432:449 arg1 acid 451:454 N-acetylneuraminic acid 432:454 N-acetylneuraminic acid 432:454 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 2 45 theme type 771:774 arg1 structures 786:795 different N-acetyllactosamine type antennary structures 741:795 different N-acetyllactosamine type antennary structures 741:795 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 1 46 theme acid 451:454 arg1 presence 420:427 the presence 416:427 the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3 416:503 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 0 47 contain contain 107:113 arg1 chains 24:29 Sialylated carbohydrate chains 0:29 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells 0:105 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 0 47 contain contain 107:113 arg2 traces 115:120 traces 115:120 traces of N-glycolylneuraminic acid 115:149 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 1 48 gly glycoprotein 403:414 arg1 glycoprotein 403:414 each glycoprotein 398:414 each glycoprotein 398:414 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 49 theme activator 245:253 arg1 variants 208:215 recombinant variants 196:215 recombinant variants 196:215 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 2 50 theme N-acetyllactosamine 751:769 arg1 structures 786:795 different N-acetyllactosamine type antennary structures 741:795 different N-acetyllactosamine type antennary structures 741:795 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 1 51 theme HPLC 152:155 arg1 analysis 157:164 HPLC analysis 152:164 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, 152:379 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 0 52 theme Chinese 79:85 arg1 cells 101:105 Chinese hamster ovary cells 79:105 Chinese hamster ovary cells 79:105 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 1 53 theme N-glycolylneuraminic 460:479 arg1 acid 481:484 N-glycolylneuraminic acid 460:484 N-glycolylneuraminic acid 460:484 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 0 54 gly glycoproteins 52:64 arg1 glycoproteins 52:64 recombinant human glycoproteins 34:64 recombinant human glycoproteins expressed in Chinese hamster ovary cells 34:105 Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. 2124546 2 55 theme N-linked 587:594 arg1 chains 609:614 the enzymatically released N-linked carbohydrate chains 560:614 the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin 560:670 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 1 56 theme human 256:260 arg1 activator 283:291 human chimeric plasminogen activator 256:291 human chimeric plasminogen activator 256:291 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 1 57 theme Chinese 352:358 arg1 cells 374:378 Chinese hamster ovary cells 352:378 Chinese hamster ovary cells 352:378 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 2124546 2 58 link linked 695:700 arg1 acid 723:726 alpha 2-3 linked N-glycolylneuraminic acid 685:726 alpha 2-3 linked N-glycolylneuraminic acid 685:726 Structural analysis by 500 MHz1H-NMR spectroscopy, of the enzymatically released N-linked carbohydrate chains of chimeric plasminogen activator and of erythropoietin, showed that alpha 2-3 linked N-glycolylneuraminic acid can occur in different N-acetyllactosamine type antennary structures. 2124546 1 59 theme chimeric 262:269 arg1 activator 283:291 human chimeric plasminogen activator 256:291 human chimeric plasminogen activator 256:291 HPLC analysis of sialic acids released from recombinant variants of human tissue plasminogen activator, human chimeric plasminogen activator, human erythropoietin, and human follitropin, expressed in Chinese hamster ovary cells, demonstrates for each glycoprotein the presence of N-acetylneuraminic acid and N-glycolylneuraminic acid in a ratio of 97:3. 7263664 0 0 theme alpha 71:75 arg1 glycoproteins 84:96 human plasma alpha 1-acid glycoproteins 58:96 human plasma alpha 1-acid glycoproteins 58:96 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 7263664 6 1 theme sugar 1012:1016 arg1 chains 1018:1023 the five sugar chains 1003:1023 the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214) 1003:1196 In addition to the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214), the structures of three new sugar chains of human alpha 1-acid glycoprotein were elucidated. 7263664 6 2 gly glycoprotein 1262:1273 arg1 glycoprotein 1262:1273 human alpha 1-acid glycoprotein 1243:1273 human alpha 1-acid glycoprotein 1243:1273 In addition to the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214), the structures of three new sugar chains of human alpha 1-acid glycoprotein were elucidated. 7263664 5 3 dep GlcNAc 980:985 arg1 leads 969:973 leads 969:973 leads to 6 969:978 In the original acidic oligosaccharides, sialic acids occur as three type linkages: NeuAc alpha 2 leads to 3Gal, NeuAc alpha 2 leads to 6Gal, and Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc. 7263664 0 4 theme plasma 64:69 arg1 glycoproteins 84:96 human plasma alpha 1-acid glycoproteins 58:96 human plasma alpha 1-acid glycoproteins 58:96 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 7263664 5 5 theme acidic 803:808 arg1 oligosaccharides 810:825 the original acidic oligosaccharides 790:825 the original acidic oligosaccharides 790:825 In the original acidic oligosaccharides, sialic acids occur as three type linkages: NeuAc alpha 2 leads to 3Gal, NeuAc alpha 2 leads to 6Gal, and Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc. 7263664 6 6 theme chains 1233:1238 arg1 structures 1203:1212 the structures 1199:1212 the structures of three new sugar chains of human alpha 1-acid glycoprotein 1199:1273 In addition to the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214), the structures of three new sugar chains of human alpha 1-acid glycoprotein were elucidated. 7263664 0 7 theme glycoproteins 84:96 arg1 moieties 38:45 the carbohydrate moieties 21:45 the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins 21:96 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 7263664 4 8 theme oligosaccharides 545:560 arg1 digestion 521:529 Sialidase digestion 511:529 Sialidase digestion of the acidic oligosaccharides from rat sample 511:576 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 5 9 theme Gal 933:935 arg1 beta 937:940 Gal beta 1 933:942 Gal beta 1 933:942 In the original acidic oligosaccharides, sialic acids occur as three type linkages: NeuAc alpha 2 leads to 3Gal, NeuAc alpha 2 leads to 6Gal, and Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc. 7263664 2 10 theme sequential 276:285 arg1 digestion 302:310 sequential exoglycosidase digestion 276:310 sequential exoglycosidase digestion 276:310 The structures of these sugar chains were studied by sequential exoglycosidase digestion in combination with methylation analysis after being released from the polypeptide back bone by hydrazinolysis. 7263664 4 11 theme triantennary 641:652 arg1 chains 673:678 three triantennary complex type sugar chains 635:678 three triantennary complex type sugar chains 635:678 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 0 12 theme 1-acid 77:82 arg1 glycoproteins 84:96 human plasma alpha 1-acid glycoproteins 58:96 human plasma alpha 1-acid glycoproteins 58:96 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 7263664 4 13 theme Sialidase 511:519 arg1 digestion 521:529 Sialidase digestion 511:529 Sialidase digestion of the acidic oligosaccharides from rat sample 511:576 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 6 14 dep Biochemistry 1170:1181 arg1 1978 1164:1167 1978 1164:1167 1978 1164:1167 In addition to the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214), the structures of three new sugar chains of human alpha 1-acid glycoprotein were elucidated. 7263664 1 15 link asparagine-linked 163:179 arg1 chains 187:192 5 and 6 acidic asparagine-linked sugar chains 148:192 5 and 6 acidic asparagine-linked sugar chains 148:192 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 1 16 contain contain 140:146 arg2 glycoproteins 126:138 Rat and human alpha 1-acid glycoproteins 99:138 Rat and human alpha 1-acid glycoproteins 99:138 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 1 16 contain contain 140:146 arg2 chains 187:192 5 and 6 acidic asparagine-linked sugar chains 148:192 5 and 6 acidic asparagine-linked sugar chains 148:192 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 1 16 contain contain 140:146 arg1 glycoproteins 126:138 Rat and human alpha 1-acid glycoproteins 99:138 Rat and human alpha 1-acid glycoproteins 99:138 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 1 16 contain contain 140:146 arg1 molecule 199:206 1 molecule 197:206 1 molecule 197:206 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 4 17 from digestion 521:529 arg1 sample 571:576 rat sample 567:576 rat sample 567:576 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 2 18 theme chains 253:258 arg1 structures 227:236 The structures 223:236 The structures of these sugar chains 223:258 The structures of these sugar chains were studied by sequential exoglycosidase digestion in combination with methylation analysis after being released from the polypeptide back bone by hydrazinolysis. 7263664 1 19 theme acidic 156:161 arg1 chains 187:192 5 and 6 acidic asparagine-linked sugar chains 148:192 5 and 6 acidic asparagine-linked sugar chains 148:192 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 6 20 theme new 1223:1225 arg1 chains 1233:1238 three new sugar chains 1217:1238 three new sugar chains of human alpha 1-acid glycoprotein 1217:1273 In addition to the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214), the structures of three new sugar chains of human alpha 1-acid glycoprotein were elucidated. 7263664 4 21 theme type 613:616 arg1 chains 624:629 three biantennary complex type sugar chains 587:629 three biantennary complex type sugar chains 587:629 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 4 21 theme type 613:616 arg1 chains 691:696 the outer chains 681:696 the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc 681:784 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 1 22 theme asparagine-linked 163:179 arg1 chains 187:192 5 and 6 acidic asparagine-linked sugar chains 148:192 5 and 6 acidic asparagine-linked sugar chains 148:192 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 0 23 theme Comparative 0:10 arg1 study 12:16 Comparative study 0:16 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 0:97 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 7263664 4 24 theme complex 605:611 arg1 chains 624:629 three biantennary complex type sugar chains 587:629 three biantennary complex type sugar chains 587:629 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 4 24 theme complex 605:611 arg1 chains 691:696 the outer chains 681:696 the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc 681:784 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 0 25 gly glycoproteins 84:96 arg1 glycoproteins 84:96 human plasma alpha 1-acid glycoproteins 58:96 human plasma alpha 1-acid glycoproteins 58:96 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 7263664 1 26 theme sugar 181:185 arg1 chains 187:192 5 and 6 acidic asparagine-linked sugar chains 148:192 5 and 6 acidic asparagine-linked sugar chains 148:192 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 4 27 theme biantennary 593:603 arg1 chains 624:629 three biantennary complex type sugar chains 587:629 three biantennary complex type sugar chains 587:629 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 4 27 theme biantennary 593:603 arg1 chains 691:696 the outer chains 681:696 the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc 681:784 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 2 28 theme exoglycosidase 287:300 arg1 digestion 302:310 sequential exoglycosidase digestion 276:310 sequential exoglycosidase digestion 276:310 The structures of these sugar chains were studied by sequential exoglycosidase digestion in combination with methylation analysis after being released from the polypeptide back bone by hydrazinolysis. 7263664 3 29 theme N-acetylneuraminic 486:503 arg1 acid 505:508 N-acetylneuraminic acid 486:508 N-acetylneuraminic acid 486:508 All oligosaccharides obtained from both glycoproteins contain N-acetylneuraminic acid. 7263664 4 30 theme Gal 758:760 arg1 beta 762:765 Gal beta 1 758:767 Gal beta 1 758:767 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 4 31 theme sugar 618:622 arg1 chains 624:629 three biantennary complex type sugar chains 587:629 three biantennary complex type sugar chains 587:629 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 4 31 theme sugar 618:622 arg1 chains 691:696 the outer chains 681:696 the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc 681:784 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 3 32 contain contain 478:484 arg2 acid 505:508 N-acetylneuraminic acid 486:508 N-acetylneuraminic acid 486:508 All oligosaccharides obtained from both glycoproteins contain N-acetylneuraminic acid. 7263664 3 32 contain contain 478:484 arg1 oligosaccharides 428:443 All oligosaccharides 424:443 All oligosaccharides obtained from both glycoproteins 424:476 All oligosaccharides obtained from both glycoproteins contain N-acetylneuraminic acid. 7263664 1 33 theme Rat 99:101 arg1 glycoproteins 126:138 Rat and human alpha 1-acid glycoproteins 99:138 Rat and human alpha 1-acid glycoproteins 99:138 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 0 34 theme moieties 38:45 arg1 study 12:16 Comparative study 0:16 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 0:97 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 7263664 2 35 theme methylation 332:342 arg1 analysis 344:351 methylation analysis 332:351 methylation analysis 332:351 The structures of these sugar chains were studied by sequential exoglycosidase digestion in combination with methylation analysis after being released from the polypeptide back bone by hydrazinolysis. 7263664 2 36 with combination 315:325 arg1 analysis 344:351 methylation analysis 332:351 methylation analysis 332:351 The structures of these sugar chains were studied by sequential exoglycosidase digestion in combination with methylation analysis after being released from the polypeptide back bone by hydrazinolysis. 7263664 6 37 theme alpha 1249:1253 arg1 glycoprotein 1262:1273 human alpha 1-acid glycoprotein 1243:1273 human alpha 1-acid glycoprotein 1243:1273 In addition to the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214), the structures of three new sugar chains of human alpha 1-acid glycoprotein were elucidated. 7263664 5 38 theme type 856:859 arg1 linkages 861:868 three type linkages 850:868 three type linkages 850:868 In the original acidic oligosaccharides, sialic acids occur as three type linkages: NeuAc alpha 2 leads to 3Gal, NeuAc alpha 2 leads to 6Gal, and Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc. 7263664 0 39 theme carbohydrate 25:36 arg1 moieties 38:45 the carbohydrate moieties 21:45 the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins 21:96 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 7263664 5 40 theme original 794:801 arg1 oligosaccharides 810:825 the original acidic oligosaccharides 790:825 the original acidic oligosaccharides 790:825 In the original acidic oligosaccharides, sialic acids occur as three type linkages: NeuAc alpha 2 leads to 3Gal, NeuAc alpha 2 leads to 6Gal, and Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc. 7263664 4 41 theme outer 685:689 arg1 chains 624:629 three biantennary complex type sugar chains 587:629 three biantennary complex type sugar chains 587:629 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 4 41 theme outer 685:689 arg1 chains 691:696 the outer chains 681:696 the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc 681:784 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 0 42 theme rat 50:52 arg1 moieties 38:45 the carbohydrate moieties 21:45 the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins 21:96 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 7263664 4 43 theme rat 567:569 arg1 sample 571:576 rat sample 567:576 rat sample 567:576 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 5 44 theme NeuAc 900:904 arg1 alpha 906:910 NeuAc alpha 2 900:912 NeuAc alpha 2 900:912 In the original acidic oligosaccharides, sialic acids occur as three type linkages: NeuAc alpha 2 leads to 3Gal, NeuAc alpha 2 leads to 6Gal, and Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc. 7263664 1 45 gly glycoproteins 126:138 arg1 glycoproteins 126:138 Rat and human alpha 1-acid glycoproteins 99:138 Rat and human alpha 1-acid glycoproteins 99:138 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 3 46 gly glycoproteins 464:476 arg1 glycoproteins 464:476 both glycoproteins 459:476 both glycoproteins 459:476 All oligosaccharides obtained from both glycoproteins contain N-acetylneuraminic acid. 7263664 1 47 theme human 107:111 arg1 1-acid 119:124 human alpha 1-acid 107:124 human alpha 1-acid 107:124 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 2 48 dep polypeptide 383:393 arg1 bone 400:403 bone 400:403 bone 400:403 The structures of these sugar chains were studied by sequential exoglycosidase digestion in combination with methylation analysis after being released from the polypeptide back bone by hydrazinolysis. 7263664 2 49 theme sugar 247:251 arg1 chains 253:258 these sugar chains 241:258 these sugar chains 241:258 The structures of these sugar chains were studied by sequential exoglycosidase digestion in combination with methylation analysis after being released from the polypeptide back bone by hydrazinolysis. 7263664 1 50 theme alpha 113:117 arg1 1-acid 119:124 human alpha 1-acid 107:124 human alpha 1-acid 107:124 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 6 51 theme glycoprotein 1262:1273 arg1 chains 1233:1238 three new sugar chains 1217:1238 three new sugar chains of human alpha 1-acid glycoprotein 1217:1273 In addition to the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214), the structures of three new sugar chains of human alpha 1-acid glycoprotein were elucidated. 7263664 4 52 theme type 662:665 arg1 chains 673:678 three triantennary complex type sugar chains 635:678 three triantennary complex type sugar chains 635:678 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 1 53 theme 1-acid 119:124 arg1 glycoproteins 126:138 Rat and human alpha 1-acid glycoproteins 99:138 Rat and human alpha 1-acid glycoproteins 99:138 Rat and human alpha 1-acid glycoproteins contain 5 and 6 acidic asparagine-linked sugar chains in 1 molecule, respectively. 7263664 6 54 theme 1-acid 1255:1260 arg1 glycoprotein 1262:1273 human alpha 1-acid glycoprotein 1243:1273 human alpha 1-acid glycoprotein 1243:1273 In addition to the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214), the structures of three new sugar chains of human alpha 1-acid glycoprotein were elucidated. 7263664 4 55 theme complex 654:660 arg1 chains 673:678 three triantennary complex type sugar chains 635:678 three triantennary complex type sugar chains 635:678 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 0 56 theme human 58:62 arg1 glycoproteins 84:96 human plasma alpha 1-acid glycoproteins 58:96 human plasma alpha 1-acid glycoproteins 58:96 Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. 7263664 6 57 theme sugar 1227:1231 arg1 chains 1233:1238 three new sugar chains 1217:1238 three new sugar chains of human alpha 1-acid glycoprotein 1217:1273 In addition to the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214), the structures of three new sugar chains of human alpha 1-acid glycoprotein were elucidated. 7263664 4 58 theme Gal 723:725 arg1 beta 727:730 Gal beta 1 723:732 Gal beta 1 723:732 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 5 59 theme NeuAc 871:875 arg1 alpha 877:881 NeuAc alpha 2 871:883 NeuAc alpha 2 871:883 In the original acidic oligosaccharides, sialic acids occur as three type linkages: NeuAc alpha 2 leads to 3Gal, NeuAc alpha 2 leads to 6Gal, and Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc. 7263664 5 60 theme sialic 828:833 arg1 acids 835:839 sialic acids 828:839 sialic acids 828:839 In the original acidic oligosaccharides, sialic acids occur as three type linkages: NeuAc alpha 2 leads to 3Gal, NeuAc alpha 2 leads to 6Gal, and Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc. 7263664 4 61 from sample 571:576 arg1 digestion 521:529 Sialidase digestion 511:529 Sialidase digestion of the acidic oligosaccharides from rat sample 511:576 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 4 61 from sample 571:576 arg1 oligosaccharides 545:560 the acidic oligosaccharides 534:560 the acidic oligosaccharides from rat sample 534:576 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 4 62 theme acidic 538:543 arg1 oligosaccharides 545:560 the acidic oligosaccharides 534:560 the acidic oligosaccharides from rat sample 534:576 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 7263664 5 63 theme NeuAc 955:959 arg1 alpha 961:965 NeuAc alpha 2 955:967 NeuAc alpha 2 955:967 In the original acidic oligosaccharides, sialic acids occur as three type linkages: NeuAc alpha 2 leads to 3Gal, NeuAc alpha 2 leads to 6Gal, and Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GlcNAc. 7263664 6 64 theme human 1243:1247 arg1 glycoprotein 1262:1273 human alpha 1-acid glycoprotein 1243:1273 human alpha 1-acid glycoprotein 1243:1273 In addition to the five sugar chains reported by Fournet, B., Montreuil, J., Strecker, G., Dorland, L., Haverkamp, J., Vilegenthart, J. F. G., Binette, J. P., and Schmid, K. ((1978) Biochemistry 17, 5206-5214), the structures of three new sugar chains of human alpha 1-acid glycoprotein were elucidated. 7263664 4 65 theme sugar 667:671 arg1 chains 673:678 three triantennary complex type sugar chains 635:678 three triantennary complex type sugar chains 635:678 Sialidase digestion of the acidic oligosaccharides from rat sample released three biantennary complex type sugar chains and three triantennary complex type sugar chains, the outer chains of which are composed of Gal beta 1 leads to 3GlcNAc and/or Gal beta 1 leads to 4GlcNAc. 11179968 7 0 theme ICAM-3 1273:1278 arg1 nonintegrin 1289:1299 the dendritic cell-specific ICAM-3 grabbing nonintegrin 1245:1299 the dendritic cell-specific ICAM-3 grabbing nonintegrin 1245:1299 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 5 1 theme Bio-Gel 683:689 arg1 chromatography 702:715 Bio-Gel P-4 column chromatography 683:715 Bio-Gel P-4 column chromatography 683:715 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 11179968 1 2 theme intercellular 161:173 arg1 ICAM 194:197 purified human intercellular adhesion molecule (ICAM)-3 146:200 purified human intercellular adhesion molecule (ICAM)-3 146:200 The N-linked oligosaccharides were released from purified human intercellular adhesion molecule (ICAM)-3 by hydrazinolysis. 11179968 7 3 theme grabbing 1280:1287 arg1 nonintegrin 1289:1299 the dendritic cell-specific ICAM-3 grabbing nonintegrin 1245:1299 the dendritic cell-specific ICAM-3 grabbing nonintegrin 1245:1299 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 7 4 located detected 1306:1313 arg2 amount 1132:1137 a small amount 1124:1137 a small amount 1124:1137 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 7 4 located detected 1306:1313 arg2 ligand 1234:1239 a ligand 1232:1239 a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin 1232:1299 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 7 4 located detected 1306:1313 arg1 addition 1114:1121 addition 1114:1121 addition 1114:1121 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 7 4 located detected 1306:1313 arg2 oligosaccharide 1164:1178 the high mannose-type oligosaccharide 1142:1178 the high mannose-type oligosaccharide with six alpha-mannose residues 1142:1210 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 5 5 theme P-4 691:693 arg1 chromatography 702:715 Bio-Gel P-4 column chromatography 683:715 Bio-Gel P-4 column chromatography 683:715 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 11179968 0 6 link N-linked 20:27 arg1 oligosaccharides 29:44 N-linked oligosaccharides 20:44 N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50) 20:94 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 1 7 theme adhesion 175:182 arg1 ICAM 194:197 purified human intercellular adhesion molecule (ICAM)-3 146:200 purified human intercellular adhesion molecule (ICAM)-3 146:200 The N-linked oligosaccharides were released from purified human intercellular adhesion molecule (ICAM)-3 by hydrazinolysis. 11179968 7 8 theme dendritic 1249:1257 arg1 nonintegrin 1289:1299 the dendritic cell-specific ICAM-3 grabbing nonintegrin 1245:1299 the dendritic cell-specific ICAM-3 grabbing nonintegrin 1245:1299 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 1 9 attach released 132:139 arg1 ICAM 194:197 purified human intercellular adhesion molecule (ICAM)-3 146:200 purified human intercellular adhesion molecule (ICAM)-3 146:200 The N-linked oligosaccharides were released from purified human intercellular adhesion molecule (ICAM)-3 by hydrazinolysis. 11179968 1 9 attach released 132:139 arg2 oligosaccharides 110:125 The N-linked oligosaccharides 97:125 The N-linked oligosaccharides 97:125 The N-linked oligosaccharides were released from purified human intercellular adhesion molecule (ICAM)-3 by hydrazinolysis. 11179968 5 10 theme column 695:700 arg1 chromatography 702:715 Bio-Gel P-4 column chromatography 683:715 Bio-Gel P-4 column chromatography 683:715 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 11179968 6 11 theme ICAM-3 882:887 arg1 oligosaccharides 862:877 N-linked oligosaccharides 853:877 N-linked oligosaccharides of ICAM-3 853:887 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 2 12 theme ICAM-3 289:294 arg1 mol 282:284 1 mol 280:284 1 mol of ICAM-3 280:294 Approximately 6 mol of oligosaccharides were released from 1 mol of ICAM-3. 11179968 3 13 theme neutral 360:366 arg1 fractions 379:387 neutral and acidic fractions 360:387 neutral and acidic fractions 360:387 The oligosaccharides reduced with NaB[3H]4 were separated into neutral and acidic fractions by paper electrophoresis. 11179968 5 14 theme serial 635:640 arg1 chromatography 656:669 serial lectin column chromatography 635:669 serial lectin column chromatography followed by Bio-Gel P-4 column chromatography 635:715 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 11179968 7 15 theme cell-specific 1259:1271 arg1 nonintegrin 1289:1299 the dendritic cell-specific ICAM-3 grabbing nonintegrin 1245:1299 the dendritic cell-specific ICAM-3 grabbing nonintegrin 1245:1299 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 6 16 theme sequential 764:773 arg1 exo- 775:778 sequential exo- 764:778 sequential exo- 764:778 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 6 17 dep three 976:980 arg1 to 973:974 to 973:974 to 973:974 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 5 18 theme column 649:654 arg1 chromatography 656:669 serial lectin column chromatography 635:669 serial lectin column chromatography followed by Bio-Gel P-4 column chromatography 635:715 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 11179968 5 19 theme lectin 642:647 arg1 chromatography 656:669 serial lectin column chromatography 635:669 serial lectin column chromatography followed by Bio-Gel P-4 column chromatography 635:715 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 11179968 1 20 theme molecule 184:191 arg1 ICAM 194:197 purified human intercellular adhesion molecule (ICAM)-3 146:200 purified human intercellular adhesion molecule (ICAM)-3 146:200 The N-linked oligosaccharides were released from purified human intercellular adhesion molecule (ICAM)-3 by hydrazinolysis. 11179968 6 21 link N-linked 853:860 arg1 oligosaccharides 862:877 N-linked oligosaccharides 853:877 N-linked oligosaccharides of ICAM-3 853:887 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 6 22 theme N-linked 853:860 arg1 oligosaccharides 862:877 N-linked oligosaccharides 853:877 N-linked oligosaccharides of ICAM-3 853:887 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 5 23 theme sialidase-treated 572:588 arg1 oligosaccharides 597:612 The neutral and sialidase-treated acidic oligosaccharides 556:612 The neutral and sialidase-treated acidic oligosaccharides 556:612 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 11179968 6 24 theme oligosaccharide 745:759 arg1 studies 729:735 Structural studies 718:735 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis 718:837 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 5 25 theme acidic 590:595 arg1 oligosaccharides 597:612 The neutral and sialidase-treated acidic oligosaccharides 556:612 The neutral and sialidase-treated acidic oligosaccharides 556:612 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 11179968 0 26 theme Structural 0:9 arg1 study 11:15 Structural study 0:15 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 0:95 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 6 27 theme complex-type 928:939 arg1 % 950:950 about 60% 942:950 about 60% 942:950 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 6 27 theme complex-type 928:939 arg1 complex-type 928:939 tri- and tetra-antennary complex-type 903:939 tri- and tetra-antennary complex-type 903:939 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 6 28 theme N-acetyllactosamine 987:1005 arg1 chains 1007:1012 two to three poly N-acetyllactosamine chains 969:1012 two to three poly N-acetyllactosamine chains terminated with the type 1 structure 969:1049 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 7 29 theme high 1146:1149 arg1 oligosaccharide 1164:1178 the high mannose-type oligosaccharide 1142:1178 the high mannose-type oligosaccharide with six alpha-mannose residues 1142:1210 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 7 30 theme alpha-mannose 1189:1201 arg1 residues 1203:1210 six alpha-mannose residues 1185:1210 six alpha-mannose residues 1185:1210 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 0 31 theme N-linked 20:27 arg1 oligosaccharides 29:44 N-linked oligosaccharides 20:44 N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50) 20:94 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 7 32 theme small 1126:1130 arg1 ligand 1234:1239 a ligand 1232:1239 a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin 1232:1299 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 7 32 theme small 1126:1130 arg1 oligosaccharide 1164:1178 the high mannose-type oligosaccharide 1142:1178 the high mannose-type oligosaccharide with six alpha-mannose residues 1142:1210 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 7 32 theme small 1126:1130 arg1 amount 1132:1137 a small amount 1124:1137 a small amount 1124:1137 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 3 33 theme acidic 372:377 arg1 fractions 379:387 neutral and acidic fractions 360:387 neutral and acidic fractions 360:387 The oligosaccharides reduced with NaB[3H]4 were separated into neutral and acidic fractions by paper electrophoresis. 11179968 6 34 theme type 1034:1037 arg1 structure 1041:1049 the type 1 structure 1030:1049 the type 1 structure 1030:1049 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 1 35 theme N-linked 101:108 arg1 oligosaccharides 110:125 The N-linked oligosaccharides 97:125 The N-linked oligosaccharides 97:125 The N-linked oligosaccharides were released from purified human intercellular adhesion molecule (ICAM)-3 by hydrazinolysis. 11179968 6 36 theme Structural 718:727 arg1 studies 729:735 Structural studies 718:735 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis 718:837 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 7 37 with oligosaccharide 1164:1178 arg1 residues 1203:1210 six alpha-mannose residues 1185:1210 six alpha-mannose residues 1185:1210 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 0 38 theme adhesion 69:76 arg1 CD50 90:93 CD50 90:93 CD50 90:93 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 0 38 theme adhesion 69:76 arg1 molecule-3 78:87 human intercellular adhesion molecule-3 49:87 human intercellular adhesion molecule-3 (CD50) 49:94 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 0 39 theme oligosaccharides 29:44 arg1 study 11:15 Structural study 0:15 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 0:95 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 4 40 theme neutral 469:475 arg1 ones 477:480 neutral ones 469:480 neutral ones 469:480 Most of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. 11179968 6 41 contain contain 961:967 arg1 % 950:950 about 60% 942:950 about 60% 942:950 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 6 41 contain contain 961:967 arg1 complex-type 928:939 tri- and tetra-antennary complex-type 903:939 tri- and tetra-antennary complex-type 903:939 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 6 41 contain contain 961:967 arg2 chains 1007:1012 two to three poly N-acetyllactosamine chains 969:1012 two to three poly N-acetyllactosamine chains terminated with the type 1 structure 969:1049 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 6 41 contain contain 961:967 arg2 those 1055:1059 those 1055:1059 those 1055:1059 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 3 42 theme paper 392:396 arg1 electrophoresis 398:412 paper electrophoresis 392:412 paper electrophoresis 392:412 The oligosaccharides reduced with NaB[3H]4 were separated into neutral and acidic fractions by paper electrophoresis. 11179968 1 43 link N-linked 101:108 arg1 oligosaccharides 110:125 The N-linked oligosaccharides 97:125 The N-linked oligosaccharides 97:125 The N-linked oligosaccharides were released from purified human intercellular adhesion molecule (ICAM)-3 by hydrazinolysis. 11179968 6 44 theme methylation 818:828 arg1 analysis 830:837 methylation analysis 818:837 methylation analysis 818:837 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 0 45 theme human 49:53 arg1 CD50 90:93 CD50 90:93 CD50 90:93 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 0 45 theme human 49:53 arg1 molecule-3 78:87 human intercellular adhesion molecule-3 49:87 human intercellular adhesion molecule-3 (CD50) 49:94 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 6 46 theme tetra-antennary 912:926 arg1 complex-type 928:939 tri- and tetra-antennary complex-type 903:939 tri- and tetra-antennary complex-type 903:939 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 7 47 theme mannose-type 1151:1162 arg1 oligosaccharide 1164:1178 the high mannose-type oligosaccharide 1142:1178 the high mannose-type oligosaccharide with six alpha-mannose residues 1142:1210 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 5 48 theme neutral 560:566 arg1 oligosaccharides 597:612 The neutral and sialidase-treated acidic oligosaccharides 556:612 The neutral and sialidase-treated acidic oligosaccharides 556:612 The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. 11179968 7 49 theme oligosaccharide 1164:1178 arg1 ligand 1234:1239 a ligand 1232:1239 a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin 1232:1299 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 7 49 theme oligosaccharide 1164:1178 arg1 oligosaccharide 1164:1178 the high mannose-type oligosaccharide 1142:1178 the high mannose-type oligosaccharide with six alpha-mannose residues 1142:1210 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 7 49 theme oligosaccharide 1164:1178 arg1 amount 1132:1137 a small amount 1124:1137 a small amount 1124:1137 In addition, a small amount of the high mannose-type oligosaccharide with six alpha-mannose residues, which could act as a ligand for the dendritic cell-specific ICAM-3 grabbing nonintegrin, was detected. 11179968 4 50 theme sialyl 536:541 arg1 they 527:530 they 527:530 they 527:530 Most of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. 11179968 4 50 theme sialyl 536:541 arg1 derivatives 543:553 sialyl derivatives 536:553 sialyl derivatives 536:553 Most of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. 11179968 2 51 attach released 266:273 arg1 mol 282:284 1 mol 280:284 1 mol of ICAM-3 280:294 Approximately 6 mol of oligosaccharides were released from 1 mol of ICAM-3. 11179968 2 51 attach released 266:273 arg2 mol 237:239 Approximately 6 mol 221:239 Approximately 6 mol of oligosaccharides 221:259 Approximately 6 mol of oligosaccharides were released from 1 mol of ICAM-3. 11179968 6 52 theme tri- 903:906 arg1 complex-type 928:939 tri- and tetra-antennary complex-type 903:939 tri- and tetra-antennary complex-type 903:939 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 4 53 with digestion 485:493 arg1 sialidase 500:508 sialidase 500:508 sialidase 500:508 Most of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. 11179968 0 54 theme molecule-3 78:87 arg1 oligosaccharides 29:44 N-linked oligosaccharides 20:44 N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50) 20:94 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 4 55 theme acidic 427:432 arg1 oligosaccharides 434:449 the acidic oligosaccharides 423:449 the acidic oligosaccharides 423:449 Most of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. 11179968 6 56 theme endo-glycosidase 784:799 arg1 digestion 801:809 endo-glycosidase digestion 784:809 endo-glycosidase digestion 784:809 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 1 57 theme purified 146:153 arg1 ICAM 194:197 purified human intercellular adhesion molecule (ICAM)-3 146:200 purified human intercellular adhesion molecule (ICAM)-3 146:200 The N-linked oligosaccharides were released from purified human intercellular adhesion molecule (ICAM)-3 by hydrazinolysis. 11179968 0 58 theme intercellular 55:67 arg1 CD50 90:93 CD50 90:93 CD50 90:93 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 0 58 theme intercellular 55:67 arg1 molecule-3 78:87 human intercellular adhesion molecule-3 49:87 human intercellular adhesion molecule-3 (CD50) 49:94 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). 11179968 6 59 theme poly 982:985 arg1 chains 1007:1012 two to three poly N-acetyllactosamine chains 969:1012 two to three poly N-acetyllactosamine chains terminated with the type 1 structure 969:1049 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 11179968 2 60 theme oligosaccharides 244:259 arg1 mol 237:239 Approximately 6 mol 221:239 Approximately 6 mol of oligosaccharides 221:259 Approximately 6 mol of oligosaccharides were released from 1 mol of ICAM-3. 11179968 1 61 theme human 155:159 arg1 ICAM 194:197 purified human intercellular adhesion molecule (ICAM)-3 146:200 purified human intercellular adhesion molecule (ICAM)-3 146:200 The N-linked oligosaccharides were released from purified human intercellular adhesion molecule (ICAM)-3 by hydrazinolysis. 11179968 6 62 theme type 1073:1076 arg1 structure 1080:1088 the type 1 structure 1069:1088 the type 1 structure 1069:1088 Structural studies of each oligosaccharide by sequential exo- and endo-glycosidase digestion and by methylation analysis revealed that N-linked oligosaccharides of ICAM-3 are mainly of tri- and tetra-antennary complex-type, about 60% of which contain two to three poly N-acetyllactosamine chains terminated with the type 1 structure and those without the type 1 structure per oligosaccharide. 6950933 0 0 theme leukaemic 83:91 arg1 cells 93:97 K-562 human leukaemic cells 71:97 K-562 human leukaemic cells 71:97 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 2 1 theme high 516:519 arg1 type 529:532 the high mannose type 512:532 the high mannose type 512:532 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 3 2 link asparagine-linked 853:869 arg1 chains 877:882 the asparagine-linked sugar chains 849:882 the asparagine-linked sugar chains of human erythrocytes 849:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 1 3 theme paper 149:153 arg1 pattern 171:177 The paper electrophoretic pattern 145:177 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis 145:269 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 1 3 theme paper 149:153 arg1 different 281:289 different 281:289 different 281:289 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 3 4 theme asparagine-linked 853:869 arg1 chains 877:882 the asparagine-linked sugar chains 849:882 the asparagine-linked sugar chains of human erythrocytes 849:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 0 5 theme human 77:81 arg1 cells 93:97 K-562 human leukaemic cells 71:97 K-562 human leukaemic cells 71:97 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 3 6 theme beta-N-acetylglucosamine 711:734 arg1 residue 736:742 the beta-N-acetylglucosamine residue 707:742 the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes 707:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 1 7 theme electrophoretic 155:169 arg1 pattern 171:177 The paper electrophoretic pattern 145:177 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis 145:269 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 1 7 theme electrophoretic 155:169 arg1 different 281:289 different 281:289 different 281:289 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 3 8 theme sugar 871:875 arg1 chains 877:882 the asparagine-linked sugar chains 849:882 the asparagine-linked sugar chains of human erythrocytes 849:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 3 9 theme core 819:822 arg1 residue 792:798 the beta-mannosyl residue 774:798 the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes 774:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 3 9 theme core 819:822 arg1 core 819:822 the trimannosyl core 803:822 the trimannosyl core 803:822 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 2 10 from chromatography 352:365 arg1 combination 370:380 combination 370:380 combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions 370:462 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 0 11 theme cells 93:97 arg1 glycoproteins 54:66 plasma membrane glycoproteins 38:66 plasma membrane glycoproteins of K-562 human leukaemic cells 38:97 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 4 12 theme K-562 1046:1050 arg1 cells 1052:1056 K-562 cells 1046:1056 K-562 cells 1046:1056 This indicates that the glucosaminyltransferase that forms the GlcNAc beta 1 leads to 4Man beta 1 leads to group has not been expressed in K-562 cells. 6950933 0 13 link asparagine-linked 4:20 arg1 chains 28:33 The asparagine-linked sugar chains 0:33 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 0:143 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 0 14 theme comparative 102:112 arg1 study 114:118 a comparative study 100:118 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 0:143 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 1 15 from that 296:299 arg1 different 281:289 different 281:289 different 281:289 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 1 15 from that 296:299 arg1 pattern 171:177 The paper electrophoretic pattern 145:177 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis 145:269 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 2 16 theme K-562 493:497 arg1 cells 499:503 K-562 cells 493:503 K-562 cells 493:503 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 3 17 attach linked 744:749 arg2 residue 736:742 the beta-N-acetylglucosamine residue 707:742 the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes 707:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 3 17 attach linked 744:749 arg3 position 762:769 the C-4 position 754:769 the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes 754:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 0 18 theme asparagine-linked 4:20 arg1 chains 28:33 The asparagine-linked sugar chains 0:33 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 0:143 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 3 19 theme C-4 758:760 arg1 position 762:769 the C-4 position 754:769 the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes 754:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 3 20 contain contained 697:705 arg2 residue 736:742 the beta-N-acetylglucosamine residue 707:742 the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes 707:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 3 20 contain contained 697:705 arg1 none 657:660 none 657:660 none of those obtained from K-562 cells 657:695 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 3 21 theme residue 792:798 arg1 position 762:769 the C-4 position 754:769 the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes 754:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 1 22 theme oligosaccharides 186:201 arg1 pattern 171:177 The paper electrophoretic pattern 145:177 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis 145:269 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 1 22 theme oligosaccharides 186:201 arg1 different 281:289 different 281:289 different 281:289 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 2 23 theme large 572:576 arg1 structures 591:600 large complex type structures 572:600 large complex type structures 572:600 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 0 24 theme sugar 22:26 arg1 chains 28:33 The asparagine-linked sugar chains 0:33 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 0:143 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 2 25 theme fractions 454:462 arg1 digestion 413:421 sequential exoglycosidase digestion 387:421 sequential exoglycosidase digestion of the neutral oligosaccharide fractions 387:462 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 0 26 theme plasma 38:43 arg1 glycoproteins 54:66 plasma membrane glycoproteins 38:66 plasma membrane glycoproteins of K-562 human leukaemic cells 38:97 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 3 27 theme beta-mannosyl 778:790 arg1 residue 792:798 the beta-mannosyl residue 774:798 the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes 774:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 3 27 theme beta-mannosyl 778:790 arg1 core 819:822 the trimannosyl core 803:822 the trimannosyl core 803:822 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 2 28 theme exoglycosidase 398:411 arg1 digestion 413:421 sequential exoglycosidase digestion 387:421 sequential exoglycosidase digestion of the neutral oligosaccharide fractions 387:462 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 2 29 theme oligosaccharide 438:452 arg1 fractions 454:462 the neutral oligosaccharide fractions 426:462 the neutral oligosaccharide fractions 426:462 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 1 30 theme human 304:308 arg1 membranes 322:330 human erythrocyte membranes 304:330 human erythrocyte membranes 304:330 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 0 31 theme human 125:129 arg1 erythrocytes 131:142 human erythrocytes 125:142 human erythrocytes 125:142 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 3 32 theme acidic 618:623 arg1 oligosaccharides 625:640 the acidic oligosaccharides 614:640 the acidic oligosaccharides 614:640 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 1 33 theme plasma 221:226 arg1 membranes 228:236 the plasma membranes 217:236 the plasma membranes of K-562 cells 217:251 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 0 34 theme glycoproteins 54:66 arg1 chains 28:33 The asparagine-linked sugar chains 0:33 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 0:143 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 1 35 theme erythrocyte 310:320 arg1 membranes 322:330 human erythrocyte membranes 304:330 human erythrocyte membranes 304:330 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 4 36 dep group 1014:1018 arg1 expressed 1033:1041 expressed 1033:1041 has not been expressed in K-562 cells 1020:1056 This indicates that the glucosaminyltransferase that forms the GlcNAc beta 1 leads to 4Man beta 1 leads to group has not been expressed in K-562 cells. 6950933 3 37 theme those 665:669 arg1 none 657:660 none 657:660 none of those obtained from K-562 cells 657:695 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 0 38 theme membrane 45:52 arg1 glycoproteins 54:66 plasma membrane glycoproteins 38:66 plasma membrane glycoproteins of K-562 human leukaemic cells 38:97 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 4 39 theme GlcNAc 970:975 arg1 beta 977:980 the GlcNAc beta 1 966:982 the GlcNAc beta 1 966:982 This indicates that the glucosaminyltransferase that forms the GlcNAc beta 1 leads to 4Man beta 1 leads to group has not been expressed in K-562 cells. 6950933 2 40 with combination 370:380 arg1 digestion 413:421 sequential exoglycosidase digestion 387:421 sequential exoglycosidase digestion of the neutral oligosaccharide fractions 387:462 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 2 41 theme column 345:350 arg1 chromatography 352:365 Bio-Gel P-4 column chromatography 333:365 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions 333:462 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 3 42 theme human 887:891 arg1 erythrocytes 893:904 human erythrocytes 887:904 human erythrocytes 887:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 3 43 theme trimannosyl 807:817 arg1 core 819:822 the trimannosyl core 803:822 the trimannosyl core 803:822 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 2 44 theme type 586:589 arg1 structures 591:600 large complex type structures 572:600 large complex type structures 572:600 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 1 45 attach released 203:210 arg1 membranes 228:236 the plasma membranes 217:236 the plasma membranes of K-562 cells 217:251 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 1 45 attach released 203:210 arg2 oligosaccharides 186:201 the oligosaccharides 182:201 the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis 182:269 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 0 46 dep chains 28:33 arg1 study 114:118 a comparative study 100:118 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 0:143 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 2 47 theme P-4 341:343 arg1 chromatography 352:365 Bio-Gel P-4 column chromatography 333:365 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions 333:462 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 3 48 theme erythrocytes 893:904 arg1 chains 877:882 the asparagine-linked sugar chains 849:882 the asparagine-linked sugar chains of human erythrocytes 849:904 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 2 49 theme complex 578:584 arg1 structures 591:600 large complex type structures 572:600 large complex type structures 572:600 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 3 50 theme K-562 685:689 arg1 cells 691:695 K-562 cells 685:695 K-562 cells 685:695 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 2 51 theme Bio-Gel 333:339 arg1 chromatography 352:365 Bio-Gel P-4 column chromatography 333:365 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions 333:462 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 0 52 theme K-562 71:75 arg1 cells 93:97 K-562 human leukaemic cells 71:97 K-562 human leukaemic cells 71:97 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 2 53 theme neutral 430:436 arg1 fractions 454:462 the neutral oligosaccharide fractions 426:462 the neutral oligosaccharide fractions 426:462 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 3 54 theme oligosaccharides 625:640 arg1 Studies 603:609 Studies 603:609 Studies of the acidic oligosaccharides 603:640 Studies of the acidic oligosaccharides indicated that none of those obtained from K-562 cells contained the beta-N-acetylglucosamine residue linked at the C-4 position of the beta-mannosyl residue of the trimannosyl core, which occurs in most of the asparagine-linked sugar chains of human erythrocytes. 6950933 2 55 theme sequential 387:396 arg1 digestion 413:421 sequential exoglycosidase digestion 387:421 sequential exoglycosidase digestion of the neutral oligosaccharide fractions 387:462 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 0 56 with study 114:118 arg1 erythrocytes 131:142 human erythrocytes 125:142 human erythrocytes 125:142 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 1 57 theme K-562 241:245 arg1 cells 247:251 K-562 cells 241:251 K-562 cells 241:251 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 6950933 2 58 theme mannose 521:527 arg1 type 529:532 the high mannose type 512:532 the high mannose type 512:532 Bio-Gel P-4 column chromatography in combination with sequential exoglycosidase digestion of the neutral oligosaccharide fractions revealed that all those from K-562 cells are of the high mannose type, while those from erythrocytes are of large complex type structures. 6950933 0 59 gly glycoproteins 54:66 arg1 glycoproteins 54:66 plasma membrane glycoproteins 38:66 plasma membrane glycoproteins of K-562 human leukaemic cells 38:97 The asparagine-linked sugar chains of plasma membrane glycoproteins of K-562 human leukaemic cells: a comparative study with human erythrocytes. 6950933 4 60 theme 4Man 993:996 arg1 beta 998:1001 4Man beta 1 993:1003 4Man beta 1 993:1003 This indicates that the glucosaminyltransferase that forms the GlcNAc beta 1 leads to 4Man beta 1 leads to group has not been expressed in K-562 cells. 6950933 1 61 theme cells 247:251 arg1 membranes 228:236 the plasma membranes 217:236 the plasma membranes of K-562 cells 217:251 The paper electrophoretic pattern of the oligosaccharides released from the plasma membranes of K-562 cells by hydrazinolysis was quite different from that of human erythrocyte membranes. 8344278 2 0 theme single 414:419 arg1 precursor 421:429 a single precursor 412:429 a single precursor 412:429 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 2 0 theme single 414:419 arg1 prosaposin 432:441 prosaposin 432:441 prosaposin 432:441 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 3 1 theme fucosylated 619:629 arg1 structure 648:656 a fucosylated trimannosyl core structure 617:656 a fucosylated trimannosyl core structure 617:656 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 4 2 contain having 934:939 arg2 residues 971:978 bisecting N-acetylglucosamine residues 941:978 bisecting N-acetylglucosamine residues (found only in this saposin) 941:1007 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 4 2 contain having 934:939 arg1 oligosaccharides 917:932 four different oligosaccharides 902:932 four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin) 902:1007 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 3 3 theme structure 648:656 arg1 predominance 601:612 the predominance 597:612 (a) the predominance of a fucosylated trimannosyl core structure 593:656 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 3 3 theme structure 648:656 arg1 features 535:542 The characteristic features 516:542 The characteristic features of the oligosaccharide moieties of saposin A 516:587 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 3 3 theme structure 648:656 arg1 occurrence 670:679 the occurrence 666:679 (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides 662:764 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 1 4 theme moieties 222:229 arg1 structures 188:197 the structures 184:197 the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease 184:310 We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. 8344278 4 5 theme bisecting 941:949 arg1 residues 971:978 bisecting N-acetylglucosamine residues 941:978 bisecting N-acetylglucosamine residues (found only in this saposin) 941:1007 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 1 6 theme patient 283:289 arg1 spleen 271:276 the spleen 267:276 the spleen of a patient with Gaucher disease 267:310 We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. 8344278 0 7 theme patient 143:149 arg1 spleen 123:128 the spleen 119:128 the spleen of a Gaucher patient 119:149 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 3 8 theme saposin 579:585 arg1 A 587:587 saposin A 579:587 saposin A 579:587 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 4 9 contain contains 777:784 arg2 presence 890:897 the presence 886:897 (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin) 882:1007 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 4 9 contain contains 777:784 arg1 C 775:775 Saposin C 767:775 Saposin C 767:775 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 4 9 contain contains 777:784 arg2 predominance 792:803 a predominance 790:803 (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides 786:876 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 4 10 theme oligosaccharides 826:841 arg1 presence 890:897 the presence 886:897 (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin) 882:1007 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 4 10 theme oligosaccharides 826:841 arg1 predominance 792:803 a predominance 790:803 (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides 786:876 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 6 11 theme possible 1155:1162 arg1 reasons 1164:1170 The possible reasons 1151:1170 The possible reasons for the unique glycosylation of each saposin 1151:1215 The possible reasons for the unique glycosylation of each saposin is discussed. 8344278 1 12 theme saposin 234:240 arg1 A 242:242 saposin A 234:242 saposin A 234:242 We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. 8344278 1 13 theme Gaucher 296:302 arg1 disease 304:310 Gaucher disease 296:310 Gaucher disease 296:310 We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. 8344278 3 14 dep occurrence 670:679 arg1 b 663:663 b 663:663 b 663:663 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 1 15 theme A 242:242 arg1 moieties 222:229 the oligosaccharide moieties 202:229 the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease 202:310 We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. 8344278 4 16 theme different 907:915 arg1 oligosaccharides 917:932 four different oligosaccharides 902:932 four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin) 902:1007 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 5 17 theme oligomannose-type 1058:1074 arg1 oligosaccharides 1076:1091 oligomannose-type oligosaccharides 1058:1091 oligomannose-type oligosaccharides 1058:1091 Saposin D is distinguished by the occurrence of oligomannose-type oligosaccharides, which comprise nearly 90% of its total oligosaccharides. 8344278 3 18 theme trimannosyl 631:641 arg1 structure 648:656 a fucosylated trimannosyl core structure 617:656 a fucosylated trimannosyl core structure 617:656 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 6 19 gly glycosylation 1187:1199 arg1 saposin 1209:1215 each saposin 1204:1215 each saposin 1204:1215 The possible reasons for the unique glycosylation of each saposin is discussed. 8344278 3 20 theme core 643:646 arg1 structure 648:656 a fucosylated trimannosyl core structure 617:656 a fucosylated trimannosyl core structure 617:656 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 2 21 attach derived 379:385 arg1 precursor 421:429 a single precursor 412:429 a single precursor 412:429 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 2 21 attach derived 379:385 arg2 saposins 319:326 These saposins 313:326 These saposins 313:326 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 2 21 attach derived 379:385 arg1 domains 401:407 separate domains 392:407 separate domains of a single precursor, prosaposin, 392:442 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 2 21 attach derived 379:385 arg2 glycoproteins 364:376 small glycoproteins 358:376 small glycoproteins 358:376 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 0 22 dep saposins 85:92 arg1 D 103:103 D 103:103 D 103:103 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 0 22 dep saposins 85:92 arg1 saposins 85:92 saposins A, C and D 85:103 saposins A, C and D 85:103 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 0 22 dep saposins 85:92 arg1 C 97:97 C 97:97 C 97:97 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 0 22 dep saposins 85:92 arg1 A 94:94 A 94:94 A 94:94 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 0 23 theme Structural 0:9 arg1 study 11:15 Structural study 0:15 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 0:150 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 3 24 dep predominance 601:612 arg1 a 594:594 a 594:594 a 594:594 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 4 25 located found 981:985 arg2 residues 971:978 bisecting N-acetylglucosamine residues 941:978 bisecting N-acetylglucosamine residues (found only in this saposin) 941:1007 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 4 25 located found 981:985 arg1 saposin 1000:1006 this saposin 995:1006 this saposin 995:1006 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 3 26 theme different 692:700 arg1 oligosaccharides 749:764 several different oligomannose-type and N-acetyllactosamine-type oligosaccharides 684:764 several different oligomannose-type and N-acetyllactosamine-type oligosaccharides 684:764 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 1 27 theme C 245:245 arg1 moieties 222:229 the oligosaccharide moieties 202:229 the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease 202:310 We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. 8344278 2 28 theme lysosomal 469:477 arg1 hydrolysis 479:488 the lysosomal hydrolysis 465:488 the lysosomal hydrolysis of various sphingolipids 465:513 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 4 29 theme Saposin 767:773 arg1 C 775:775 Saposin C 767:775 Saposin C 767:775 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 2 30 theme small 358:362 arg1 saposins 319:326 These saposins 313:326 These saposins 313:326 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 2 30 theme small 358:362 arg1 glycoproteins 364:376 small glycoproteins 358:376 small glycoproteins 358:376 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 3 31 theme A 587:587 arg1 moieties 567:574 the oligosaccharide moieties 547:574 the oligosaccharide moieties of saposin A 547:587 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 2 32 theme separate 392:399 arg1 precursor 421:429 a single precursor 412:429 a single precursor 412:429 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 2 32 theme separate 392:399 arg1 domains 401:407 separate domains 392:407 separate domains of a single precursor, prosaposin, 392:442 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 0 33 theme moieties 40:47 arg1 study 11:15 Structural study 0:15 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 0:150 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 1 34 theme D 251:251 arg1 moieties 222:229 the oligosaccharide moieties 202:229 the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease 202:310 We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. 8344278 3 35 theme characteristic 520:533 arg1 predominance 601:612 the predominance 597:612 (a) the predominance of a fucosylated trimannosyl core structure 593:656 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 3 35 theme characteristic 520:533 arg1 features 535:542 The characteristic features 516:542 The characteristic features of the oligosaccharide moieties of saposin A 516:587 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 6 36 theme saposin 1209:1215 arg1 glycosylation 1187:1199 the unique glycosylation 1176:1199 the unique glycosylation of each saposin 1176:1215 The possible reasons for the unique glycosylation of each saposin is discussed. 8344278 0 37 theme oligosaccharide 24:38 arg1 moieties 40:47 the oligosaccharide moieties 20:47 the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient 20:149 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 3 38 gly fucosylated 619:629 arg1 structure 648:656 a fucosylated trimannosyl core structure 617:656 a fucosylated trimannosyl core structure 617:656 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 4 39 dep presence 890:897 arg1 b 883:883 b 883:883 b 883:883 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 2 40 theme saposin 343:349 arg1 B 351:351 saposin B 343:351 saposin B 343:351 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 0 41 theme sphingolipid 52:63 arg1 saposins 85:92 saposins A, C and D 85:103 saposins A, C and D 85:103 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 0 41 theme sphingolipid 52:63 arg1 proteins 75:82 sphingolipid activator proteins 52:82 sphingolipid activator proteins 52:82 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 3 42 theme several 684:690 arg1 oligosaccharides 749:764 several different oligomannose-type and N-acetyllactosamine-type oligosaccharides 684:764 several different oligomannose-type and N-acetyllactosamine-type oligosaccharides 684:764 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 2 43 theme sphingolipids 501:513 arg1 hydrolysis 479:488 the lysosomal hydrolysis 465:488 the lysosomal hydrolysis of various sphingolipids 465:513 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 2 44 theme precursor 421:429 arg1 precursor 421:429 a single precursor 412:429 a single precursor 412:429 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 2 44 theme precursor 421:429 arg1 domains 401:407 separate domains 392:407 separate domains of a single precursor, prosaposin, 392:442 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 5 45 theme oligosaccharides 1076:1091 arg1 occurrence 1044:1053 the occurrence 1040:1053 the occurrence of oligomannose-type oligosaccharides, which comprise nearly 90% of its total oligosaccharides 1040:1148 Saposin D is distinguished by the occurrence of oligomannose-type oligosaccharides, which comprise nearly 90% of its total oligosaccharides. 8344278 4 46 dep predominance 792:803 arg1 a 787:787 a 787:787 a 787:787 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 4 47 theme monoantennary 847:859 arg1 oligosaccharides 861:876 monoantennary oligosaccharides 847:876 monoantennary oligosaccharides 847:876 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 2 48 theme various 493:499 arg1 sphingolipids 501:513 various sphingolipids 493:513 various sphingolipids 493:513 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 4 49 theme oligosaccharides 917:932 arg1 presence 890:897 the presence 886:897 (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin) 882:1007 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 4 49 theme oligosaccharides 917:932 arg1 predominance 792:803 a predominance 790:803 (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides 786:876 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 5 50 theme total 1127:1131 arg1 oligosaccharides 1133:1148 its total oligosaccharides 1123:1148 its total oligosaccharides 1123:1148 Saposin D is distinguished by the occurrence of oligomannose-type oligosaccharides, which comprise nearly 90% of its total oligosaccharides. 8344278 0 51 theme Gaucher 135:141 arg1 patient 143:149 a Gaucher patient 133:149 a Gaucher patient 133:149 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 5 52 theme Saposin 1010:1016 arg1 D 1018:1018 Saposin D 1010:1018 Saposin D 1010:1018 Saposin D is distinguished by the occurrence of oligomannose-type oligosaccharides, which comprise nearly 90% of its total oligosaccharides. 8344278 3 53 theme oligosaccharide 551:565 arg1 moieties 567:574 the oligosaccharide moieties 547:574 the oligosaccharide moieties of saposin A 547:587 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 3 54 theme N-acetyllactosamine-type 724:747 arg1 oligosaccharides 749:764 several different oligomannose-type and N-acetyllactosamine-type oligosaccharides 684:764 several different oligomannose-type and N-acetyllactosamine-type oligosaccharides 684:764 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 4 55 theme oligosaccharides 861:876 arg1 presence 890:897 the presence 886:897 (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin) 882:1007 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 4 55 theme oligosaccharides 861:876 arg1 predominance 792:803 a predominance 790:803 (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides 786:876 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 3 56 theme moieties 567:574 arg1 predominance 601:612 the predominance 597:612 (a) the predominance of a fucosylated trimannosyl core structure 593:656 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 3 56 theme moieties 567:574 arg1 features 535:542 The characteristic features 516:542 The characteristic features of the oligosaccharide moieties of saposin A 516:587 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 4 57 theme oligomannose-type 808:824 arg1 oligosaccharides 826:841 oligomannose-type oligosaccharides 808:841 oligomannose-type oligosaccharides 808:841 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 3 58 theme oligosaccharides 749:764 arg1 predominance 601:612 the predominance 597:612 (a) the predominance of a fucosylated trimannosyl core structure 593:656 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 3 58 theme oligosaccharides 749:764 arg1 features 535:542 The characteristic features 516:542 The characteristic features of the oligosaccharide moieties of saposin A 516:587 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 3 58 theme oligosaccharides 749:764 arg1 occurrence 670:679 the occurrence 666:679 (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides 662:764 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 0 59 theme proteins 75:82 arg1 moieties 40:47 the oligosaccharide moieties 20:47 the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient 20:149 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 5 60 theme oligosaccharides 1133:1148 arg1 % 1118:1118 nearly 90% 1109:1118 nearly 90% of its total oligosaccharides 1109:1148 Saposin D is distinguished by the occurrence of oligomannose-type oligosaccharides, which comprise nearly 90% of its total oligosaccharides. 8344278 5 60 theme oligosaccharides 1133:1148 arg1 oligosaccharides 1133:1148 its total oligosaccharides 1123:1148 its total oligosaccharides 1123:1148 Saposin D is distinguished by the occurrence of oligomannose-type oligosaccharides, which comprise nearly 90% of its total oligosaccharides. 8344278 3 61 theme oligomannose-type 702:718 arg1 oligosaccharides 749:764 several different oligomannose-type and N-acetyllactosamine-type oligosaccharides 684:764 several different oligomannose-type and N-acetyllactosamine-type oligosaccharides 684:764 The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. 8344278 0 62 theme activator 65:73 arg1 saposins 85:92 saposins A, C and D 85:103 saposins A, C and D 85:103 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 0 62 theme activator 65:73 arg1 proteins 75:82 sphingolipid activator proteins 52:82 sphingolipid activator proteins 52:82 Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. 8344278 4 63 theme N-acetylglucosamine 951:969 arg1 residues 971:978 bisecting N-acetylglucosamine residues 941:978 bisecting N-acetylglucosamine residues (found only in this saposin) 941:1007 Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). 8344278 2 64 gly glycoproteins 364:376 arg1 saposins 319:326 These saposins 313:326 These saposins 313:326 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 2 64 gly glycoproteins 364:376 arg1 glycoproteins 364:376 small glycoproteins 358:376 small glycoproteins 358:376 These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. 8344278 6 65 theme unique 1180:1185 arg1 glycosylation 1187:1199 the unique glycosylation 1176:1199 the unique glycosylation of each saposin 1176:1215 The possible reasons for the unique glycosylation of each saposin is discussed. 8344278 1 66 with patient 283:289 arg1 disease 304:310 Gaucher disease 296:310 Gaucher disease 296:310 We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. 8344278 1 67 theme oligosaccharide 206:220 arg1 moieties 222:229 the oligosaccharide moieties 202:229 the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease 202:310 We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. 2110822 5 0 theme Fuc 1585:1587 arg1 alpha 1589:1593 Fuc alpha 1----6 1585:1600 Fuc alpha 1----6 1585:1600 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 0 theme Fuc 1585:1587 arg1 beta 1573:1576 Man beta 1----4GlcNAc beta 1----4 1551:1583 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 3 1 theme different 701:709 arg1 specificities 732:744 different carbohydrate-binding specificities 701:744 different carbohydrate-binding specificities 701:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 5 2 theme beta 1469:1472 arg1 GlcNAcOT 1498:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 2 theme beta 1469:1472 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 1 3 theme normal 247:252 arg1 liver 260:264 normal human liver 247:264 normal human liver 247:264 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 2 4 attach released 354:361 arg1 samples 382:388 the two SAP-1 samples 368:388 the two SAP-1 samples 368:388 Oligosaccharides released from the two SAP-1 samples by hydrazinolysis were fractionated by paper electrophoresis and by Aleuria aurantia lectin-Sepharose and Bio-Gel P-4 (under 400 mesh) column chromatography. 2110822 2 4 attach released 354:361 arg2 Oligosaccharides 337:352 Oligosaccharides 337:352 Oligosaccharides released from the two SAP-1 samples by hydrazinolysis 337:406 Oligosaccharides released from the two SAP-1 samples by hydrazinolysis were fractionated by paper electrophoresis and by Aleuria aurantia lectin-Sepharose and Bio-Gel P-4 (under 400 mesh) column chromatography. 2110822 4 5 theme gangliosidosis 930:943 arg1 liver 954:958 GM1 gangliosidosis (type 1) liver 926:958 GM1 gangliosidosis (type 1) liver 926:958 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 0 6 link asparagine-linked 19:35 arg1 chains 43:48 asparagine-linked sugar chains 19:48 asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver 19:155 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 5 7 theme Man 1551:1553 arg1 alpha 1589:1593 Fuc alpha 1----6 1585:1600 Fuc alpha 1----6 1585:1600 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 7 theme Man 1551:1553 arg1 beta 1573:1576 Man beta 1----4GlcNAc beta 1----4 1551:1583 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 3 8 theme sequential 758:767 arg1 digestion 769:777 sequential digestion 758:777 sequential digestion by exoglycosidases with different aglycon specificities 758:833 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 5 9 theme alpha 1435:1439 arg1 beta 1469:1472 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4 1431:1479 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 9 theme alpha 1435:1439 arg1 alpha 1485:1489 Fuc alpha 1----6 1481:1496 Fuc alpha 1----6 1481:1496 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 10 theme Man 1234:1236 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 10 theme Man 1234:1236 arg1 GlcNAcOT 1602:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 10 theme Man 1234:1236 arg1 beta 1530:1533 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 10 theme Man 1234:1236 arg1 alpha 1281:1285 Man alpha 1----6 1277:1292 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 10 theme Man 1234:1236 arg1 GlcNAcOT 1498:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 10 theme Man 1234:1236 arg1 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 10 theme Man 1234:1236 arg1 beta 1619:1622 GlcNAc beta 1----4GlcNAcOT 1612:1637 GlcNAc beta 1----4GlcNAcOT 1612:1637 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 10 theme Man 1234:1236 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 10 theme Man 1234:1236 arg1 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 4 11 theme normal 898:903 arg1 liver 911:915 normal human liver 898:915 normal human liver 898:915 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 5 12 theme 1----4GlcNAc 1560:1571 arg1 alpha 1589:1593 Fuc alpha 1----6 1585:1600 Fuc alpha 1----6 1585:1600 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 12 theme 1----4GlcNAc 1560:1571 arg1 beta 1573:1576 Man beta 1----4GlcNAc beta 1----4 1551:1583 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 13 theme beta 1392:1395 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 13 theme beta 1392:1395 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 3 14 with columns 688:694 arg1 specificities 732:744 different carbohydrate-binding specificities 701:744 different carbohydrate-binding specificities 701:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 1 15 theme sugar 176:180 arg1 chains 182:187 Asparagine-linked sugar chains 158:187 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver 158:302 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 6 16 theme beta-galactosidase 1854:1871 arg1 activity 1873:1880 acid beta-galactosidase activity 1849:1880 acid beta-galactosidase activity 1849:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 5 17 theme GlcNAc 1612:1617 arg1 beta 1619:1622 GlcNAc beta 1----4GlcNAcOT 1612:1637 GlcNAc beta 1----4GlcNAcOT 1612:1637 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 17 theme GlcNAc 1612:1617 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 18 theme 1----4GlcNAcOT 1624:1637 arg1 beta 1619:1622 GlcNAc beta 1----4GlcNAcOT 1612:1637 GlcNAc beta 1----4GlcNAcOT 1612:1637 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 18 theme 1----4GlcNAcOT 1624:1637 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 0 19 theme GM1 123:125 arg1 type 143:146 type 1 143:148 type 1 143:148 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 0 19 theme GM1 123:125 arg1 gangliosidosis 127:140 GM1 gangliosidosis 123:140 GM1 gangliosidosis (type 1) 123:149 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 1 20 theme activator 205:213 arg1 protein 215:221 sphingolipid activator protein 1 192:223 sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver 192:302 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 1 20 theme activator 205:213 arg1 SAP-1 226:230 SAP-1 226:230 SAP-1 226:230 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 6 21 theme metabolic 1829:1837 arg1 defect 1839:1844 a metabolic defect 1827:1844 a metabolic defect in acid beta-galactosidase activity 1827:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 5 22 theme following 1099:1107 arg1 chains 1069:1074 The sugar chains 1059:1074 The sugar chains of the former 1059:1088 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 22 theme following 1099:1107 arg1 products 1127:1134 the following eight degradation products 1095:1134 the following eight degradation products from complex-type sugar chains 1095:1165 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 4 23 theme type 946:949 arg1 liver 954:958 GM1 gangliosidosis (type 1) liver 926:958 GM1 gangliosidosis (type 1) liver 926:958 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 6 24 theme complex-type 1765:1776 arg1 chains 1784:1789 tetraantennary complex-type sugar chains 1750:1789 tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity 1750:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 3 25 theme aglycon 813:819 arg1 specificities 821:833 different aglycon specificities 803:833 different aglycon specificities 803:833 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 1 26 dep liver 260:264 arg1 liver 298:302 liver 298:302 liver 298:302 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 5 27 theme Man 1294:1296 arg1 alpha 1281:1285 Man alpha 1----6 1277:1292 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 27 theme Man 1294:1296 arg1 alpha 1298:1302 Man alpha 1----3 1294:1309 Man alpha 1----3 1294:1309 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 3 28 theme molecular 640:648 arg1 sizes 650:654 their effective molecular sizes 624:654 their effective molecular sizes 624:654 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 29 from fraction 587:594 arg1 Structures 548:557 Structures 548:557 Structures of oligosaccharides in each fraction 548:594 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 30 theme methylation 840:850 arg1 analysis 852:859 methylation analysis 840:859 methylation analysis 840:859 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 4 31 from other 985:989 arg1 different 965:973 different 965:973 different 965:973 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 5 32 theme sugar 1154:1158 arg1 chains 1160:1165 complex-type sugar chains 1141:1165 complex-type sugar chains 1141:1165 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 2 33 theme P-4 504:506 arg1 chromatography 532:545 Bio-Gel P-4 (under 400 mesh) column chromatography 496:545 Bio-Gel P-4 (under 400 mesh) column chromatography 496:545 Oligosaccharides released from the two SAP-1 samples by hydrazinolysis were fractionated by paper electrophoresis and by Aleuria aurantia lectin-Sepharose and Bio-Gel P-4 (under 400 mesh) column chromatography. 2110822 6 34 theme latter 1700:1705 arg1 chains 1686:1691 the sugar chains 1676:1691 the sugar chains of the latter 1676:1705 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 6 34 theme latter 1700:1705 arg1 mono- 1741:1745 sialylated and nonsialylated mono- 1712:1745 sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity 1712:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 5 35 theme Man 1277:1279 arg1 alpha 1281:1285 Man alpha 1----6 1277:1292 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 35 theme Man 1277:1279 arg1 alpha 1349:1353 Fuc alpha 1----6 1345:1360 Fuc alpha 1----6 1345:1360 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 35 theme Man 1277:1279 arg1 alpha 1298:1302 Man alpha 1----3 1294:1309 Man alpha 1----3 1294:1309 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 35 theme Man 1277:1279 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 2 36 theme column 525:530 arg1 chromatography 532:545 Bio-Gel P-4 (under 400 mesh) column chromatography 496:545 Bio-Gel P-4 (under 400 mesh) column chromatography 496:545 Oligosaccharides released from the two SAP-1 samples by hydrazinolysis were fractionated by paper electrophoresis and by Aleuria aurantia lectin-Sepharose and Bio-Gel P-4 (under 400 mesh) column chromatography. 2110822 0 37 theme normal 100:105 arg1 liver 113:117 normal human liver 100:117 normal human liver 100:117 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 5 38 theme degradation 1115:1125 arg1 chains 1069:1074 The sugar chains 1059:1074 The sugar chains of the former 1059:1088 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 38 theme degradation 1115:1125 arg1 products 1127:1134 the following eight degradation products 1095:1134 the following eight degradation products from complex-type sugar chains 1095:1165 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 0 39 dep liver 113:117 arg1 liver 151:155 liver 151:155 liver 151:155 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 6 40 theme sugar 1680:1684 arg1 chains 1686:1691 the sugar chains 1676:1691 the sugar chains of the latter 1676:1705 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 6 40 theme sugar 1680:1684 arg1 mono- 1741:1745 sialylated and nonsialylated mono- 1712:1745 sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity 1712:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 5 41 theme beta 1451:1454 arg1 beta 1469:1472 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4 1431:1479 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 41 theme beta 1451:1454 arg1 alpha 1485:1489 Fuc alpha 1----6 1481:1496 Fuc alpha 1----6 1481:1496 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 3 42 from behavior 657:664 arg1 columns 688:694 immobilized lectin columns 669:694 immobilized lectin columns with different carbohydrate-binding specificities 669:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 1 43 link Asparagine-linked 158:174 arg1 chains 182:187 Asparagine-linked sugar chains 158:187 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver 158:302 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 5 44 theme Fuc 1345:1347 arg1 alpha 1281:1285 Man alpha 1----6 1277:1292 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 44 theme Fuc 1345:1347 arg1 alpha 1349:1353 Fuc alpha 1----6 1345:1360 Fuc alpha 1----6 1345:1360 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 2 45 theme SAP-1 376:380 arg1 samples 382:388 the two SAP-1 samples 368:388 the two SAP-1 samples 368:388 Oligosaccharides released from the two SAP-1 samples by hydrazinolysis were fractionated by paper electrophoresis and by Aleuria aurantia lectin-Sepharose and Bio-Gel P-4 (under 400 mesh) column chromatography. 2110822 5 46 theme alpha 1204:1208 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 46 theme alpha 1204:1208 arg1 GlcNAcOT 1602:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 46 theme alpha 1204:1208 arg1 beta 1530:1533 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 46 theme alpha 1204:1208 arg1 alpha 1281:1285 Man alpha 1----6 1277:1292 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 46 theme alpha 1204:1208 arg1 GlcNAcOT 1498:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 46 theme alpha 1204:1208 arg1 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 46 theme alpha 1204:1208 arg1 beta 1619:1622 GlcNAc beta 1----4GlcNAcOT 1612:1637 GlcNAc beta 1----4GlcNAcOT 1612:1637 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 46 theme alpha 1204:1208 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 46 theme alpha 1204:1208 arg1 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 47 dep exoglycosidases 1170:1184 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 47 dep exoglycosidases 1170:1184 arg1 GlcNAcOT 1602:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 47 dep exoglycosidases 1170:1184 arg1 beta 1530:1533 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 47 dep exoglycosidases 1170:1184 arg1 alpha 1281:1285 Man alpha 1----6 1277:1292 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 47 dep exoglycosidases 1170:1184 arg1 GlcNAcOT 1498:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 47 dep exoglycosidases 1170:1184 arg1 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 47 dep exoglycosidases 1170:1184 arg1 beta 1619:1622 GlcNAc beta 1----4GlcNAcOT 1612:1637 GlcNAc beta 1----4GlcNAcOT 1612:1637 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 47 dep exoglycosidases 1170:1184 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 47 dep exoglycosidases 1170:1184 arg1 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 48 theme beta 1512:1515 arg1 beta 1530:1533 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 48 theme beta 1512:1515 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 6 49 from defect 1839:1844 arg1 activity 1873:1880 acid beta-galactosidase activity 1849:1880 acid beta-galactosidase activity 1849:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 5 50 theme Man 1311:1313 arg1 beta 1333:1336 Man beta 1----4GlcNAc beta 1----4 1311:1343 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 0 51 theme asparagine-linked 19:35 arg1 chains 43:48 asparagine-linked sugar chains 19:48 asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver 19:155 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 5 52 theme 1----4GlcNAc 1320:1331 arg1 beta 1333:1336 Man beta 1----4GlcNAc beta 1----4 1311:1343 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 3 53 from data 616:619 arg1 behavior 657:664 behavior 657:664 behavior on immobilized lectin columns with different carbohydrate-binding specificities 657:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 53 from data 616:619 arg1 sizes 650:654 their effective molecular sizes 624:654 their effective molecular sizes 624:654 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 53 from data 616:619 arg1 analysis 852:859 methylation analysis 840:859 methylation analysis 840:859 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 53 from data 616:619 arg1 results 747:753 results 747:753 results of sequential digestion by exoglycosidases with different aglycon specificities 747:833 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 0 54 theme chains 43:48 arg1 Characteristics 0:14 Characteristics 0:14 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 0:156 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 5 55 from exoglycosidases 1170:1184 arg1 lysosomes 1189:1197 lysosomes 1189:1197 lysosomes 1189:1197 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 4 56 theme sugar 1045:1049 arg1 chains 1051:1056 complex-type sugar chains 1032:1056 complex-type sugar chains 1032:1056 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 6 57 theme nonsialylated 1727:1739 arg1 mono- 1741:1745 sialylated and nonsialylated mono- 1712:1745 sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity 1712:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 6 57 theme nonsialylated 1727:1739 arg1 chains 1686:1691 the sugar chains 1676:1691 the sugar chains of the latter 1676:1705 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 0 58 theme protein 76:82 arg1 chains 43:48 asparagine-linked sugar chains 19:48 asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver 19:155 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 5 59 theme Man 1372:1374 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 59 theme Man 1372:1374 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 0 60 theme sphingolipid 53:64 arg1 protein 76:82 sphingolipid activator protein 1 53:84 sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver 53:155 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 5 61 theme sugar 1063:1067 arg1 chains 1069:1074 The sugar chains 1059:1074 The sugar chains of the former 1059:1088 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 61 theme sugar 1063:1067 arg1 products 1127:1134 the following eight degradation products 1095:1134 the following eight degradation products from complex-type sugar chains 1095:1165 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 6 62 theme sialylated 1712:1721 arg1 mono- 1741:1745 sialylated and nonsialylated mono- 1712:1745 sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity 1712:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 6 62 theme sialylated 1712:1721 arg1 chains 1686:1691 the sugar chains 1676:1691 the sugar chains of the latter 1676:1705 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 5 63 dep alpha 1281:1285 arg1 beta 1333:1336 Man beta 1----4GlcNAc beta 1----4 1311:1343 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 64 theme 1----6Man 1382:1390 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 64 theme 1----6Man 1382:1390 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 65 theme beta 1238:1241 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 65 theme beta 1238:1241 arg1 GlcNAcOT 1602:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 65 theme beta 1238:1241 arg1 beta 1530:1533 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 65 theme beta 1238:1241 arg1 alpha 1281:1285 Man alpha 1----6 1277:1292 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 65 theme beta 1238:1241 arg1 GlcNAcOT 1498:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 65 theme beta 1238:1241 arg1 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 65 theme beta 1238:1241 arg1 beta 1619:1622 GlcNAc beta 1----4GlcNAcOT 1612:1637 GlcNAc beta 1----4GlcNAcOT 1612:1637 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 65 theme beta 1238:1241 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 65 theme beta 1238:1241 arg1 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 66 theme beta 1573:1576 arg1 GlcNAcOT 1602:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 66 theme beta 1573:1576 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 3 67 theme lectin 681:686 arg1 columns 688:694 immobilized lectin columns 669:694 immobilized lectin columns with different carbohydrate-binding specificities 669:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 4 68 theme Sugar 862:866 arg1 chains 868:873 Sugar chains 862:873 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver 862:958 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 5 69 theme beta 1256:1259 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 69 theme beta 1256:1259 arg1 GlcNAcOT 1602:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 69 theme beta 1256:1259 arg1 beta 1530:1533 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 69 theme beta 1256:1259 arg1 alpha 1281:1285 Man alpha 1----6 1277:1292 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 69 theme beta 1256:1259 arg1 GlcNAcOT 1498:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 69 theme beta 1256:1259 arg1 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 69 theme beta 1256:1259 arg1 beta 1619:1622 GlcNAc beta 1----4GlcNAcOT 1612:1637 GlcNAc beta 1----4GlcNAcOT 1612:1637 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 69 theme beta 1256:1259 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 69 theme beta 1256:1259 arg1 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 2 70 theme aurantia 466:473 arg1 lectin-Sepharose 475:490 Aleuria aurantia lectin-Sepharose 458:490 Aleuria aurantia lectin-Sepharose 458:490 Oligosaccharides released from the two SAP-1 samples by hydrazinolysis were fractionated by paper electrophoresis and by Aleuria aurantia lectin-Sepharose and Bio-Gel P-4 (under 400 mesh) column chromatography. 2110822 3 71 from sizes 650:654 arg1 columns 688:694 immobilized lectin columns 669:694 immobilized lectin columns with different carbohydrate-binding specificities 669:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 72 theme carbohydrate-binding 711:730 arg1 specificities 732:744 different carbohydrate-binding specificities 701:744 different carbohydrate-binding specificities 701:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 5 73 theme Man 1431:1433 arg1 beta 1469:1472 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4 1431:1479 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 73 theme Man 1431:1433 arg1 alpha 1485:1489 Fuc alpha 1----6 1481:1496 Fuc alpha 1----6 1481:1496 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 1 74 theme human 254:258 arg1 liver 260:264 normal human liver 247:264 normal human liver 247:264 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 4 75 theme GM1 926:928 arg1 liver 954:958 GM1 gangliosidosis (type 1) liver 926:958 GM1 gangliosidosis (type 1) liver 926:958 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 5 76 theme beta 1555:1558 arg1 alpha 1589:1593 Fuc alpha 1----6 1585:1600 Fuc alpha 1----6 1585:1600 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 76 theme beta 1555:1558 arg1 beta 1573:1576 Man beta 1----4GlcNAc beta 1----4 1551:1583 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 3 77 theme digestion 769:777 arg1 behavior 657:664 behavior 657:664 behavior on immobilized lectin columns with different carbohydrate-binding specificities 657:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 77 theme digestion 769:777 arg1 sizes 650:654 their effective molecular sizes 624:654 their effective molecular sizes 624:654 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 77 theme digestion 769:777 arg1 analysis 852:859 methylation analysis 840:859 methylation analysis 840:859 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 77 theme digestion 769:777 arg1 results 747:753 results 747:753 results of sequential digestion by exoglycosidases with different aglycon specificities 747:833 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 5 78 theme 1----6Man 1441:1449 arg1 beta 1469:1472 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4 1431:1479 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 78 theme 1----6Man 1441:1449 arg1 alpha 1485:1489 Fuc alpha 1----6 1481:1496 Fuc alpha 1----6 1481:1496 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 1 79 theme Asparagine-linked 158:174 arg1 chains 182:187 Asparagine-linked sugar chains 158:187 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver 158:302 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 5 80 from chains 1160:1165 arg1 chains 1069:1074 The sugar chains 1059:1074 The sugar chains of the former 1059:1088 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 80 from chains 1160:1165 arg1 products 1127:1134 the following eight degradation products 1095:1134 the following eight degradation products from complex-type sugar chains 1095:1165 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 4 81 attach derived 1019:1025 arg2 them 1009:1012 them 1009:1012 them 1009:1012 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 4 81 attach derived 1019:1025 arg2 both 1001:1004 both 1001:1004 both 1001:1004 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 4 81 attach derived 1019:1025 arg1 chains 1051:1056 complex-type sugar chains 1032:1056 complex-type sugar chains 1032:1056 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 3 82 from results 747:753 arg1 columns 688:694 immobilized lectin columns 669:694 immobilized lectin columns with different carbohydrate-binding specificities 669:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 5 83 theme 1----4GlcNAc 1397:1408 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 83 theme 1----4GlcNAc 1397:1408 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 4 84 theme human 905:909 arg1 liver 911:915 normal human liver 898:915 normal human liver 898:915 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 6 85 theme acid 1849:1852 arg1 activity 1873:1880 acid beta-galactosidase activity 1849:1880 acid beta-galactosidase activity 1849:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 3 86 theme different 803:811 arg1 specificities 821:833 different aglycon specificities 803:833 different aglycon specificities 803:833 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 87 theme oligosaccharides 562:577 arg1 Structures 548:557 Structures 548:557 Structures of oligosaccharides in each fraction 548:594 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 1 88 theme sphingolipid 192:203 arg1 protein 215:221 sphingolipid activator protein 1 192:223 sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver 192:302 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 1 88 theme sphingolipid 192:203 arg1 SAP-1 226:230 SAP-1 226:230 SAP-1 226:230 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 1 89 theme protein 215:221 arg1 chains 182:187 Asparagine-linked sugar chains 158:187 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver 158:302 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 6 90 dep these 1669:1673 arg1 contrast 1657:1664 contrast 1657:1664 contrast 1657:1664 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 3 91 from oligosaccharides 562:577 arg1 fraction 587:594 each fraction 582:594 each fraction 582:594 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 3 92 theme effective 630:638 arg1 sizes 650:654 their effective molecular sizes 624:654 their effective molecular sizes 624:654 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 5 93 theme former 1083:1088 arg1 chains 1069:1074 The sugar chains 1059:1074 The sugar chains of the former 1059:1088 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 93 theme former 1083:1088 arg1 products 1127:1134 the following eight degradation products 1095:1134 the following eight degradation products from complex-type sugar chains 1095:1165 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 2 94 theme Bio-Gel 496:502 arg1 chromatography 532:545 Bio-Gel P-4 (under 400 mesh) column chromatography 496:545 Bio-Gel P-4 (under 400 mesh) column chromatography 496:545 Oligosaccharides released from the two SAP-1 samples by hydrazinolysis were fractionated by paper electrophoresis and by Aleuria aurantia lectin-Sepharose and Bio-Gel P-4 (under 400 mesh) column chromatography. 2110822 5 95 theme Fuc 1481:1483 arg1 beta 1469:1472 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4 1431:1479 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 95 theme Fuc 1481:1483 arg1 alpha 1485:1489 Fuc alpha 1----6 1481:1496 Fuc alpha 1----6 1481:1496 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 6 96 gly nonsialylated 1727:1739 arg1 mono- 1741:1745 sialylated and nonsialylated mono- 1712:1745 sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity 1712:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 6 96 gly nonsialylated 1727:1739 arg1 chains 1686:1691 the sugar chains 1676:1691 the sugar chains of the latter 1676:1705 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 3 97 from Structures 548:557 arg1 fraction 587:594 each fraction 582:594 each fraction 582:594 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 0 98 theme human 107:111 arg1 liver 113:117 normal human liver 100:117 normal human liver 100:117 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 6 99 gly sialylated 1712:1721 arg1 mono- 1741:1745 sialylated and nonsialylated mono- 1712:1745 sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity 1712:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 6 99 gly sialylated 1712:1721 arg1 chains 1686:1691 the sugar chains 1676:1691 the sugar chains of the latter 1676:1705 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 5 100 theme 1----4GlcNAc 1456:1467 arg1 beta 1469:1472 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4 1431:1479 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 100 theme 1----4GlcNAc 1456:1467 arg1 alpha 1485:1489 Fuc alpha 1----6 1481:1496 Fuc alpha 1----6 1481:1496 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 101 theme complex-type 1141:1152 arg1 chains 1160:1165 complex-type sugar chains 1141:1165 complex-type sugar chains 1141:1165 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 3 102 with exoglycosidases 782:796 arg1 specificities 821:833 different aglycon specificities 803:833 different aglycon specificities 803:833 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 6 103 theme sugar 1778:1782 arg1 chains 1784:1789 tetraantennary complex-type sugar chains 1750:1789 tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity 1750:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 0 104 theme sugar 37:41 arg1 chains 43:48 asparagine-linked sugar chains 19:48 asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver 19:155 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 1 105 theme GM1 270:272 arg1 gangliosidosis 274:287 GM1 gangliosidosis 270:287 GM1 gangliosidosis (type 1) 270:296 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 1 105 theme GM1 270:272 arg1 type 290:293 type 1 290:295 type 1 290:295 Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. 2110822 2 106 theme paper 429:433 arg1 electrophoresis 435:449 paper electrophoresis 429:449 paper electrophoresis 429:449 Oligosaccharides released from the two SAP-1 samples by hydrazinolysis were fractionated by paper electrophoresis and by Aleuria aurantia lectin-Sepharose and Bio-Gel P-4 (under 400 mesh) column chromatography. 2110822 6 107 theme tetraantennary 1750:1763 arg1 chains 1784:1789 tetraantennary complex-type sugar chains 1750:1789 tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity 1750:1880 In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. 2110822 5 108 theme 1----4GlcNAc 1517:1528 arg1 beta 1530:1533 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 108 theme 1----4GlcNAc 1517:1528 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 109 theme beta 1315:1318 arg1 beta 1333:1336 Man beta 1----4GlcNAc beta 1----4 1311:1343 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 110 theme Man 1217:1219 arg1 alpha 1221:1225 Man alpha 1----3 1217:1232 Man alpha 1----3 1217:1232 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 110 theme Man 1217:1219 arg1 alpha 1204:1208 Man alpha 1----6 1200:1215 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 0 111 theme activator 66:74 arg1 protein 76:82 sphingolipid activator protein 1 53:84 sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver 53:155 Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. 2110822 4 112 theme complex-type 1032:1043 arg1 chains 1051:1056 complex-type sugar chains 1032:1056 complex-type sugar chains 1032:1056 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 3 113 from analysis 852:859 arg1 columns 688:694 immobilized lectin columns 669:694 immobilized lectin columns with different carbohydrate-binding specificities 669:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 4 114 theme SAP-1 878:882 arg1 chains 868:873 Sugar chains 862:873 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver 862:958 Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. 2110822 5 115 theme alpha 1376:1380 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 115 theme alpha 1376:1380 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 116 theme Man 1200:1202 arg1 alpha 1221:1225 Man alpha 1----3 1217:1232 Man alpha 1----3 1217:1232 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 116 theme Man 1200:1202 arg1 alpha 1204:1208 Man alpha 1----6 1200:1215 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 117 theme Man 1508:1510 arg1 beta 1530:1533 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 117 theme Man 1508:1510 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 3 118 theme immobilized 669:679 arg1 columns 688:694 immobilized lectin columns 669:694 immobilized lectin columns with different carbohydrate-binding specificities 669:744 Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. 2110822 5 119 theme 1----4GlcNAc 1243:1254 arg1 beta 1410:1413 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1372:1428 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 119 theme 1----4GlcNAc 1243:1254 arg1 GlcNAcOT 1602:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1551:1609 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 119 theme 1----4GlcNAc 1243:1254 arg1 beta 1530:1533 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1508:1548 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 119 theme 1----4GlcNAc 1243:1254 arg1 alpha 1281:1285 Man alpha 1----6 1277:1292 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4 1277:1343 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 119 theme 1----4GlcNAc 1243:1254 arg1 GlcNAcOT 1498:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT 1431:1505 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 119 theme 1----4GlcNAc 1243:1254 arg1 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 GlcNAcOT 1644:1651 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 119 theme 1----4GlcNAc 1243:1254 arg1 beta 1619:1622 GlcNAc beta 1----4GlcNAcOT 1612:1637 GlcNAc beta 1----4GlcNAcOT 1612:1637 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 119 theme 1----4GlcNAc 1243:1254 arg1 1----4GlcNAcOT 1261:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT 1200:1274 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 2110822 5 119 theme 1----4GlcNAc 1243:1254 arg1 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 GlcNAcOT 1362:1369 The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. 3462190 0 0 theme leukemia 95:102 arg1 cells 104:108 chronic myelogenous leukemia cells 75:108 chronic myelogenous leukemia cells 75:108 Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. 3462190 2 1 theme column 407:412 arg1 chromatography 414:427 QAE-Sephadex column chromatography 394:427 QAE-Sephadex column chromatography 394:427 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 1 2 theme leukemia 273:280 arg1 cells 282:286 acute myelogenous leukemia cells 255:286 acute myelogenous leukemia cells 255:286 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 0 3 theme myelogenous 83:93 arg1 leukemia 95:102 chronic myelogenous leukemia 75:102 chronic myelogenous leukemia cells 75:108 Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. 3462190 6 4 theme cell 1368:1371 arg1 lineage 1373:1379 the same cell lineage 1359:1379 the same cell lineage 1359:1379 (formula: see text) These results suggest that structures of O-linked oligosaccharides vary in the different maturation stages along the same cell lineage. 3462190 2 5 theme QAE-Sephadex 394:405 arg1 chromatography 414:427 QAE-Sephadex column chromatography 394:427 QAE-Sephadex column chromatography 394:427 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 3 6 contain contain 686:692 arg1 granulocytes 634:645 normal granulocytes 627:645 normal granulocytes 627:645 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 3 6 contain contain 686:692 arg1 cells 680:684 chronic myelogenous leukemia cells 651:684 chronic myelogenous leukemia cells 651:684 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 3 6 contain contain 686:692 arg2 series 696:701 a series 694:701 a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 694:816 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 4 7 theme polylactosaminyl 934:949 arg1 oligosaccharides 951:966 these polylactosaminyl oligosaccharides 928:966 these polylactosaminyl oligosaccharides 928:966 However, these polylactosaminyl oligosaccharides were barely detectable in chronic myelogenous leukemia cells. 3462190 0 8 link O-linked 14:21 arg1 oligosaccharides 23:38 O-linked oligosaccharides 14:38 O-linked oligosaccharides 14:38 Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. 3462190 5 9 theme other 1037:1041 arg1 hand 1043:1046 the other hand 1033:1046 the other hand 1033:1046 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 3 10 theme polylactosaminyl 852:867 arg1 oligosaccharides 869:884 polylactosaminyl oligosaccharides 852:884 polylactosaminyl oligosaccharides 852:884 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 3 11 theme leukemia 671:678 arg1 cells 680:684 chronic myelogenous leukemia cells 651:684 chronic myelogenous leukemia cells 651:684 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 3 12 from = 814:814 arg1 granulocytes 799:810 normal granulocytes 792:810 normal granulocytes 792:810 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 1 13 theme alkaline 291:298 arg1 treatment 312:320 alkaline borohydride treatment 291:320 alkaline borohydride treatment 291:320 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 0 14 theme acute 115:119 arg1 leukemia 133:140 acute myelogenous leukemia 115:140 acute myelogenous leukemia cells 115:146 Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. 3462190 5 15 theme 2----6-linked 1188:1200 arg1 acid 1209:1212 2----6-linked sialic acid 1188:1212 2----6-linked sialic acid 1188:1212 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 3 16 dep see 772:774 arg1 formula 763:769 formula 763:769 formula 763:769 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 2 17 theme fast 470:473 arg1 spectrometry 497:508 fast atom bombardment-mass spectrometry 470:508 fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments 470:606 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 3 18 dep contain 686:692 arg1 major 821:825 major 821:825 major 821:825 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 4 19 from cells 1023:1027 arg1 detectable 980:989 detectable 980:989 detectable 980:989 However, these polylactosaminyl oligosaccharides were barely detectable in chronic myelogenous leukemia cells. 3462190 1 20 attach isolated 180:187 arg1 granulocytes 201:212 normal granulocytes 194:212 normal granulocytes 194:212 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 1 20 attach isolated 180:187 arg1 cells 282:286 acute myelogenous leukemia cells 255:286 acute myelogenous leukemia cells 255:286 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 1 20 attach isolated 180:187 arg2 oligosaccharides 158:173 O-Linked oligosaccharides 149:173 O-Linked oligosaccharides 149:173 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 1 20 attach isolated 180:187 arg1 cells 244:248 chronic myelogenous leukemia cells 215:248 chronic myelogenous leukemia cells 215:248 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 3 21 theme normal 627:632 arg1 granulocytes 634:645 normal granulocytes 627:645 normal granulocytes 627:645 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 1 22 theme normal 194:199 arg1 granulocytes 201:212 normal granulocytes 194:212 normal granulocytes 194:212 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 3 23 link O-linked 706:713 arg1 oligosaccharides 715:730 O-linked oligosaccharides 706:730 O-linked oligosaccharides with the following structure, (formula: see text) 706:780 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 6 24 theme maturation 1335:1344 arg1 stages 1346:1351 the different maturation stages 1321:1351 the different maturation stages along the same cell lineage 1321:1379 (formula: see text) These results suggest that structures of O-linked oligosaccharides vary in the different maturation stages along the same cell lineage. 3462190 2 25 theme exoglycosidase 582:595 arg1 treatments 597:606 specific exoglycosidase treatments 573:606 specific exoglycosidase treatments 573:606 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 2 26 theme Sephadex 361:368 arg1 G-50 370:373 Sephadex G-50 361:373 Sephadex G-50 gel filtration 361:388 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 5 27 link 2----6-linked 1188:1200 arg1 acid 1209:1212 2----6-linked sialic acid 1188:1212 2----6-linked sialic acid 1188:1212 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 3 28 dep series 696:701 arg1 = 814:814 = 814:814 = 814:814 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 3 29 from granulocytes 799:810 arg1 = 814:814 = 814:814 = 814:814 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 1 30 theme borohydride 300:310 arg1 treatment 312:320 alkaline borohydride treatment 291:320 alkaline borohydride treatment 291:320 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 6 31 theme different 1325:1333 arg1 stages 1346:1351 the different maturation stages 1321:1351 the different maturation stages along the same cell lineage 1321:1379 (formula: see text) These results suggest that structures of O-linked oligosaccharides vary in the different maturation stages along the same cell lineage. 3462190 5 32 theme myeloid 1121:1127 arg1 cells 1129:1133 poorly differentiated myeloid cells 1099:1133 poorly differentiated myeloid cells 1099:1133 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 6 33 dep see 1236:1238 arg1 formula 1227:1233 formula 1227:1233 formula 1227:1233 (formula: see text) These results suggest that structures of O-linked oligosaccharides vary in the different maturation stages along the same cell lineage. 3462190 0 34 theme oligosaccharides 23:38 arg1 Structures 0:9 Structures 0:9 Structures of O-linked oligosaccharides 0:38 Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. 3462190 0 35 theme leukemia 133:140 arg1 cells 142:146 acute myelogenous leukemia cells 115:146 acute myelogenous leukemia cells 115:146 Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. 3462190 6 36 theme oligosaccharides 1296:1311 arg1 structures 1273:1282 structures 1273:1282 structures of O-linked oligosaccharides 1273:1311 (formula: see text) These results suggest that structures of O-linked oligosaccharides vary in the different maturation stages along the same cell lineage. 3462190 3 37 theme chronic 651:657 arg1 cells 680:684 chronic myelogenous leukemia cells 651:684 chronic myelogenous leukemia cells 651:684 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 5 38 with oligosaccharides 1166:1181 arg1 acid 1209:1212 2----6-linked sialic acid 1188:1212 2----6-linked sialic acid 1188:1212 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 1 39 theme chronic 215:221 arg1 leukemia 235:242 chronic myelogenous leukemia 215:242 chronic myelogenous leukemia cells 215:248 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 0 40 theme O-linked 14:21 arg1 oligosaccharides 23:38 O-linked oligosaccharides 14:38 O-linked oligosaccharides 14:38 Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. 3462190 0 41 theme myelogenous 121:131 arg1 leukemia 133:140 acute myelogenous leukemia 115:140 acute myelogenous leukemia cells 115:146 Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. 3462190 3 42 theme myelogenous 659:669 arg1 cells 680:684 chronic myelogenous leukemia cells 651:684 chronic myelogenous leukemia cells 651:684 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 1 43 theme myelogenous 223:233 arg1 leukemia 235:242 chronic myelogenous leukemia 215:242 chronic myelogenous leukemia cells 215:248 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 4 44 theme leukemia 1014:1021 arg1 cells 1023:1027 chronic myelogenous leukemia cells 994:1027 chronic myelogenous leukemia cells 994:1027 However, these polylactosaminyl oligosaccharides were barely detectable in chronic myelogenous leukemia cells. 3462190 5 45 theme short 1151:1155 arg1 oligosaccharides 1166:1181 short O-linked oligosaccharides 1151:1181 short O-linked oligosaccharides with 2----6-linked sialic acid 1151:1212 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 6 46 theme same 1363:1366 arg1 lineage 1373:1379 the same cell lineage 1359:1379 the same cell lineage 1359:1379 (formula: see text) These results suggest that structures of O-linked oligosaccharides vary in the different maturation stages along the same cell lineage. 3462190 1 47 theme leukemia 235:242 arg1 cells 244:248 chronic myelogenous leukemia cells 215:248 chronic myelogenous leukemia cells 215:248 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 5 48 contain contain 1143:1149 arg1 cells 1076:1080 acute myelogenous leukemia cells 1049:1080 acute myelogenous leukemia cells 1049:1080 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 5 48 contain contain 1143:1149 arg2 oligosaccharides 1166:1181 short O-linked oligosaccharides 1151:1181 short O-linked oligosaccharides with 2----6-linked sialic acid 1151:1212 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 5 48 contain contain 1143:1149 arg2 cells 1076:1080 acute myelogenous leukemia cells 1049:1080 acute myelogenous leukemia cells 1049:1080 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 5 48 contain contain 1143:1149 arg1 hand 1043:1046 the other hand 1033:1046 the other hand 1033:1046 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 4 49 theme myelogenous 1002:1012 arg1 leukemia 1014:1021 chronic myelogenous leukemia 994:1021 chronic myelogenous leukemia cells 994:1027 However, these polylactosaminyl oligosaccharides were barely detectable in chronic myelogenous leukemia cells. 3462190 3 50 theme following 741:749 arg1 structure 751:759 the following structure 737:759 the following structure, (formula: see text) 737:780 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 6 51 dep results 1252:1258 arg1 see 1236:1238 see 1236:1238 see text 1236:1243 (formula: see text) These results suggest that structures of O-linked oligosaccharides vary in the different maturation stages along the same cell lineage. 3462190 2 52 theme methylation 535:545 arg1 analysis 547:554 methylation analysis 535:554 methylation analysis 535:554 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 3 53 with oligosaccharides 715:730 arg1 structure 751:759 the following structure 737:759 the following structure, (formula: see text) 737:780 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 3 54 theme normal 792:797 arg1 granulocytes 799:810 normal granulocytes 792:810 normal granulocytes 792:810 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 0 55 theme normal 54:59 arg1 granulocytes 61:72 normal granulocytes 54:72 normal granulocytes 54:72 Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. 3462190 6 56 link O-linked 1287:1294 arg1 oligosaccharides 1296:1311 O-linked oligosaccharides 1287:1311 O-linked oligosaccharides 1287:1311 (formula: see text) These results suggest that structures of O-linked oligosaccharides vary in the different maturation stages along the same cell lineage. 3462190 4 57 theme chronic 994:1000 arg1 leukemia 1014:1021 chronic myelogenous leukemia 994:1021 chronic myelogenous leukemia cells 994:1027 However, these polylactosaminyl oligosaccharides were barely detectable in chronic myelogenous leukemia cells. 3462190 4 58 from detectable 980:989 arg1 cells 1023:1027 chronic myelogenous leukemia cells 994:1027 chronic myelogenous leukemia cells 994:1027 However, these polylactosaminyl oligosaccharides were barely detectable in chronic myelogenous leukemia cells. 3462190 5 59 theme differentiated 1106:1119 arg1 cells 1129:1133 poorly differentiated myeloid cells 1099:1133 poorly differentiated myeloid cells 1099:1133 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 5 60 theme O-linked 1157:1164 arg1 oligosaccharides 1166:1181 short O-linked oligosaccharides 1151:1181 short O-linked oligosaccharides with 2----6-linked sialic acid 1151:1212 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 3 61 theme oligosaccharides 715:730 arg1 series 696:701 a series 694:701 a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 694:816 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 6 62 theme O-linked 1287:1294 arg1 oligosaccharides 1296:1311 O-linked oligosaccharides 1287:1311 O-linked oligosaccharides 1287:1311 (formula: see text) These results suggest that structures of O-linked oligosaccharides vary in the different maturation stages along the same cell lineage. 3462190 5 63 theme myelogenous 1055:1065 arg1 leukemia 1067:1074 acute myelogenous leukemia 1049:1074 acute myelogenous leukemia cells 1049:1080 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 2 64 theme gel 375:377 arg1 filtration 379:388 Sephadex G-50 gel filtration 361:388 Sephadex G-50 gel filtration 361:388 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 5 65 theme acute 1049:1053 arg1 leukemia 1067:1074 acute myelogenous leukemia 1049:1074 acute myelogenous leukemia cells 1049:1080 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 5 66 theme leukemia 1067:1074 arg1 cells 1076:1080 acute myelogenous leukemia cells 1049:1080 acute myelogenous leukemia cells 1049:1080 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 2 67 theme G-50 370:373 arg1 filtration 379:388 Sephadex G-50 gel filtration 361:388 Sephadex G-50 gel filtration 361:388 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 3 68 dep structure 751:759 arg1 see 772:774 see 772:774 see text 772:779 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 0 69 theme chronic 75:81 arg1 leukemia 95:102 chronic myelogenous leukemia 75:102 chronic myelogenous leukemia cells 75:108 Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. 3462190 3 70 theme O-linked 706:713 arg1 oligosaccharides 715:730 O-linked oligosaccharides 706:730 O-linked oligosaccharides with the following structure, (formula: see text) 706:780 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 2 71 theme atom 475:478 arg1 spectrometry 497:508 fast atom bombardment-mass spectrometry 470:508 fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments 470:606 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 1 72 theme O-Linked 149:156 arg1 oligosaccharides 158:173 O-Linked oligosaccharides 149:173 O-Linked oligosaccharides 149:173 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 3 73 theme minor 901:905 arg1 components 907:916 minor components 901:916 minor components 901:916 Results show that normal granulocytes and chronic myelogenous leukemia cells contain a series of O-linked oligosaccharides with the following structure, (formula: see text) where, in normal granulocytes n = 0 is major and n = 1 or 2, and thus polylactosaminyl oligosaccharides are present as minor components. 3462190 1 74 theme acute 255:259 arg1 leukemia 273:280 acute myelogenous leukemia 255:280 acute myelogenous leukemia cells 255:286 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 3462190 2 75 theme specific 573:580 arg1 treatments 597:606 specific exoglycosidase treatments 573:606 specific exoglycosidase treatments 573:606 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 2 76 theme bombardment-mass 480:495 arg1 spectrometry 497:508 fast atom bombardment-mass spectrometry 470:508 fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments 470:606 Oligosaccharides were fractionated by Sephadex G-50 gel filtration and QAE-Sephadex column chromatography, and their structures were elucidated by fast atom bombardment-mass spectrometry after permethylation and methylation analysis before and after specific exoglycosidase treatments. 3462190 5 77 theme sialic 1202:1207 arg1 acid 1209:1212 2----6-linked sialic acid 1188:1212 2----6-linked sialic acid 1188:1212 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 5 78 link O-linked 1157:1164 arg1 oligosaccharides 1166:1181 short O-linked oligosaccharides 1151:1181 short O-linked oligosaccharides with 2----6-linked sialic acid 1151:1212 On the other hand, acute myelogenous leukemia cells, which represent poorly differentiated myeloid cells, mainly contain short O-linked oligosaccharides with 2----6-linked sialic acid as follows. 3462190 1 79 theme myelogenous 261:271 arg1 leukemia 273:280 acute myelogenous leukemia 255:280 acute myelogenous leukemia cells 255:286 O-Linked oligosaccharides were isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells by alkaline borohydride treatment. 7140761 0 0 theme patients 115:122 arg1 glycoproteins 98:110 bronchial-mucus glycoproteins 82:110 bronchial-mucus glycoproteins of patients suffering from cystic fibrosis 82:153 Primary-structure determination of fourteen neutral oligosaccharides derived from bronchial-mucus glycoproteins of patients suffering from cystic fibrosis, employing 500-MHz 1H-NMR spectroscopy. 7140761 8 1 theme GlcNAc 1106:1111 arg1 element 1087:1093 common structural element 1069:1093 common structural element 1069:1093 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 8 1 theme GlcNAc 1106:1111 arg1 beta 1113:1116 the other GlcNAc(beta 1 1096:1118 the other GlcNAc(beta 1 leads to 3)GalNAc-ol 1096:1139 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 7 2 theme core 996:999 arg1 disaccharide 1001:1012 the core disaccharide 992:1012 the core disaccharide 992:1012 The structures can be divided into two groups depending on the core disaccharide. 7140761 8 3 theme other 1100:1104 arg1 element 1087:1093 common structural element 1069:1093 common structural element 1069:1093 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 8 3 theme other 1100:1104 arg1 beta 1113:1116 the other GlcNAc(beta 1 1096:1118 the other GlcNAc(beta 1 leads to 3)GalNAc-ol 1096:1139 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 8 4 dep Gal 1034:1036 arg1 leads 1045:1049 leads 1045:1049 leads to 3 1045:1054 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 10 5 theme glycoproteins 1494:1506 arg1 chains 1473:1478 oligosaccharide chains 1457:1478 oligosaccharide chains of mucin-type glycoproteins 1457:1506 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 8 6 dep beta 1113:1116 arg1 leads 1120:1124 leads 1120:1124 leads to 3)GalNAc-ol 1120:1139 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 8 7 theme structural 1076:1085 arg1 element 1087:1093 common structural element 1069:1093 common structural element 1069:1093 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 8 7 theme structural 1076:1085 arg1 beta 1113:1116 the other GlcNAc(beta 1 1096:1118 the other GlcNAc(beta 1 leads to 3)GalNAc-ol 1096:1139 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 6 8 theme oligosaccharide-alditols 907:930 arg1 mixtures 895:902 mixtures 895:902 mixtures of oligosaccharide-alditols 895:930 500-MHz 1H-NMR spectroscopy was found to be effective in detecting heterogeneity and to be invaluable for the determination of structures in mixtures of oligosaccharide-alditols. 7140761 1 9 theme 500-MHz 323:329 arg1 spectroscopy 338:349 500-MHz 1H-NMR spectroscopy 323:349 500-MHz 1H-NMR spectroscopy 323:349 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients was investigated by 500-MHz 1H-NMR spectroscopy and methylation analysis. 7140761 10 10 dep see 1312:1314 arg1 formula 1303:1309 formula 1303:1309 formula 1303:1309 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 8 11 theme common 1069:1074 arg1 element 1087:1093 common structural element 1069:1093 common structural element 1069:1093 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 8 11 theme common 1069:1074 arg1 beta 1113:1116 the other GlcNAc(beta 1 1096:1118 the other GlcNAc(beta 1 leads to 3)GalNAc-ol 1096:1139 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 0 12 gly glycoproteins 98:110 arg1 glycoproteins 98:110 bronchial-mucus glycoproteins 82:110 bronchial-mucus glycoproteins of patients suffering from cystic fibrosis 82:153 Primary-structure determination of fourteen neutral oligosaccharides derived from bronchial-mucus glycoproteins of patients suffering from cystic fibrosis, employing 500-MHz 1H-NMR spectroscopy. 7140761 1 13 theme 1H-NMR 331:336 arg1 spectroscopy 338:349 500-MHz 1H-NMR spectroscopy 323:349 500-MHz 1H-NMR spectroscopy 323:349 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients was investigated by 500-MHz 1H-NMR spectroscopy and methylation analysis. 7140761 1 14 gly glycoproteins 250:262 arg1 glycoproteins 250:262 bronchial-mucus glycoproteins 234:262 bronchial-mucus glycoproteins obtained from cystic fibrosis patients 234:301 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients was investigated by 500-MHz 1H-NMR spectroscopy and methylation analysis. 7140761 6 15 from determination 864:876 arg1 mixtures 895:902 mixtures 895:902 mixtures of oligosaccharide-alditols 895:930 500-MHz 1H-NMR spectroscopy was found to be effective in detecting heterogeneity and to be invaluable for the determination of structures in mixtures of oligosaccharide-alditols. 7140761 0 16 theme cystic 139:144 arg1 fibrosis 146:153 cystic fibrosis 139:153 cystic fibrosis 139:153 Primary-structure determination of fourteen neutral oligosaccharides derived from bronchial-mucus glycoproteins of patients suffering from cystic fibrosis, employing 500-MHz 1H-NMR spectroscopy. 7140761 5 17 theme primary 715:721 arg1 structure 723:731 the primary structure 711:731 the primary structure 711:731 For all 14 compounds the primary structure could be elucidated. 7140761 10 18 theme oligosaccharide 1457:1471 arg1 chains 1473:1478 oligosaccharide chains 1457:1478 oligosaccharide chains of mucin-type glycoproteins 1457:1506 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 10 19 theme groups 1290:1295 arg1 representatives 1263:1277 The most complex representatives 1246:1277 The most complex representatives of the two groups 1246:1295 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 1 20 theme carbohydrate 212:223 arg1 units 225:229 carbohydrate units 212:229 carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients 212:301 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients was investigated by 500-MHz 1H-NMR spectroscopy and methylation analysis. 7140761 3 21 theme Neutral 455:461 arg1 oligosaccharide-alditols 463:486 Neutral oligosaccharide-alditols 455:486 Neutral oligosaccharide-alditols 455:486 Neutral oligosaccharide-alditols, ranging in size from disaccharides to pentasaccharides, were isolated. 7140761 6 22 theme structures 881:890 arg1 determination 864:876 the determination 860:876 the determination of structures in mixtures of oligosaccharide-alditols 860:930 500-MHz 1H-NMR spectroscopy was found to be effective in detecting heterogeneity and to be invaluable for the determination of structures in mixtures of oligosaccharide-alditols. 7140761 1 23 theme units 225:229 arg1 structure 199:207 The structure 195:207 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients 195:301 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients was investigated by 500-MHz 1H-NMR spectroscopy and methylation analysis. 7140761 0 24 theme Primary-structure 0:16 arg1 determination 18:30 Primary-structure determination 0:30 Primary-structure determination of fourteen neutral oligosaccharides 0:67 Primary-structure determination of fourteen neutral oligosaccharides derived from bronchial-mucus glycoproteins of patients suffering from cystic fibrosis, employing 500-MHz 1H-NMR spectroscopy. 7140761 10 25 theme mucin-type 1483:1492 arg1 glycoproteins 1494:1506 mucin-type glycoproteins 1483:1506 mucin-type glycoproteins 1483:1506 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 10 26 theme blood-group-H 1407:1419 arg1 determinant 1421:1431 the type-1 blood-group-H determinant 1396:1431 the type-1 blood-group-H determinant 1396:1431 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 10 27 theme structural 1337:1346 arg1 sequences 1444:1452 novel sequences 1438:1452 novel sequences in oligosaccharide chains of mucin-type glycoproteins 1438:1506 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 10 27 theme structural 1337:1346 arg1 elements 1348:1355 The italicized structural elements 1322:1355 The italicized structural elements 1322:1355 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 1 28 theme bronchial-mucus 234:248 arg1 glycoproteins 250:262 bronchial-mucus glycoproteins 234:262 bronchial-mucus glycoproteins obtained from cystic fibrosis patients 234:301 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients was investigated by 500-MHz 1H-NMR spectroscopy and methylation analysis. 7140761 1 29 theme methylation 355:365 arg1 analysis 367:374 methylation analysis 355:374 methylation analysis 355:374 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients was investigated by 500-MHz 1H-NMR spectroscopy and methylation analysis. 7140761 10 30 theme italicized 1326:1335 arg1 sequences 1444:1452 novel sequences 1438:1452 novel sequences in oligosaccharide chains of mucin-type glycoproteins 1438:1506 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 10 30 theme italicized 1326:1335 arg1 elements 1348:1355 The italicized structural elements 1322:1355 The italicized structural elements 1322:1355 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 1 31 theme glycoproteins 250:262 arg1 units 225:229 carbohydrate units 212:229 carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients 212:301 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients was investigated by 500-MHz 1H-NMR spectroscopy and methylation analysis. 7140761 0 32 theme oligosaccharides 52:67 arg1 determination 18:30 Primary-structure determination 0:30 Primary-structure determination of fourteen neutral oligosaccharides 0:67 Primary-structure determination of fourteen neutral oligosaccharides derived from bronchial-mucus glycoproteins of patients suffering from cystic fibrosis, employing 500-MHz 1H-NMR spectroscopy. 7140761 0 33 theme 1H-NMR 174:179 arg1 spectroscopy 181:192 500-MHz 1H-NMR spectroscopy 166:192 500-MHz 1H-NMR spectroscopy 166:192 Primary-structure determination of fourteen neutral oligosaccharides derived from bronchial-mucus glycoproteins of patients suffering from cystic fibrosis, employing 500-MHz 1H-NMR spectroscopy. 7140761 10 34 theme complex 1255:1261 arg1 representatives 1263:1277 The most complex representatives 1246:1277 The most complex representatives of the two groups 1246:1295 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 6 35 theme 1H-NMR 762:767 arg1 spectroscopy 769:780 500-MHz 1H-NMR spectroscopy 754:780 500-MHz 1H-NMR spectroscopy 754:780 500-MHz 1H-NMR spectroscopy was found to be effective in detecting heterogeneity and to be invaluable for the determination of structures in mixtures of oligosaccharide-alditols. 7140761 10 36 gly glycoproteins 1494:1506 arg1 glycoproteins 1494:1506 mucin-type glycoproteins 1483:1506 mucin-type glycoproteins 1483:1506 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 0 37 theme neutral 44:50 arg1 oligosaccharides 52:67 fourteen neutral oligosaccharides 35:67 fourteen neutral oligosaccharides 35:67 Primary-structure determination of fourteen neutral oligosaccharides derived from bronchial-mucus glycoproteins of patients suffering from cystic fibrosis, employing 500-MHz 1H-NMR spectroscopy. 7140761 0 38 theme 500-MHz 166:172 arg1 spectroscopy 181:192 500-MHz 1H-NMR spectroscopy 166:192 500-MHz 1H-NMR spectroscopy 166:192 Primary-structure determination of fourteen neutral oligosaccharides derived from bronchial-mucus glycoproteins of patients suffering from cystic fibrosis, employing 500-MHz 1H-NMR spectroscopy. 7140761 8 39 theme Gal 1034:1036 arg1 GalNAc-ol 1056:1064 Gal(beta 1 leads to 3)GalNAc-ol 1034:1064 Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol 1034:1139 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 8 40 dep GalNAc-ol 1131:1139 arg1 3 1129:1129 3 1129:1129 3 1129:1129 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 8 41 contain contains 1025:1032 arg2 GalNAc-ol 1056:1064 Gal(beta 1 leads to 3)GalNAc-ol 1034:1064 Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol 1034:1139 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 8 41 contain contains 1025:1032 arg1 group 1019:1023 One group 1015:1023 One group 1015:1023 One group contains Gal(beta 1 leads to 3)GalNAc-ol as common structural element, the other GlcNAc(beta 1 leads to 3)GalNAc-ol. 7140761 6 42 theme 500-MHz 754:760 arg1 spectroscopy 769:780 500-MHz 1H-NMR spectroscopy 754:780 500-MHz 1H-NMR spectroscopy 754:780 500-MHz 1H-NMR spectroscopy was found to be effective in detecting heterogeneity and to be invaluable for the determination of structures in mixtures of oligosaccharide-alditols. 7140761 10 43 theme novel 1438:1442 arg1 sequences 1444:1452 novel sequences 1438:1452 novel sequences in oligosaccharide chains of mucin-type glycoproteins 1438:1506 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 10 43 theme novel 1438:1442 arg1 elements 1348:1355 The italicized structural elements 1322:1355 The italicized structural elements 1322:1355 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 9 44 theme other 1190:1194 arg1 extensions 1226:1235 extensions 1226:1235 extensions thereof 1226:1243 Both disaccharides were identified as such; the other compounds can be conceived as extensions thereof. 7140761 9 44 theme other 1190:1194 arg1 compounds 1196:1204 the other compounds 1186:1204 the other compounds 1186:1204 Both disaccharides were identified as such; the other compounds can be conceived as extensions thereof. 7140761 10 45 from sequences 1444:1452 arg1 chains 1473:1478 oligosaccharide chains 1457:1478 oligosaccharide chains of mucin-type glycoproteins 1457:1506 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 1 46 theme cystic 278:283 arg1 fibrosis 285:292 cystic fibrosis 278:292 cystic fibrosis patients 278:301 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients was investigated by 500-MHz 1H-NMR spectroscopy and methylation analysis. 7140761 10 47 theme SSEA-1 1373:1378 arg1 determinant 1380:1390 the SSEA-1 determinant 1369:1390 the SSEA-1 determinant 1369:1390 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 10 48 theme type-1 1400:1405 arg1 determinant 1421:1431 the type-1 blood-group-H determinant 1396:1431 the type-1 blood-group-H determinant 1396:1431 The most complex representatives of the two groups are: (formula; see text) The italicized structural elements, comprising the SSEA-1 determinant and the type-1 blood-group-H determinant, are novel sequences in oligosaccharide chains of mucin-type glycoproteins. 7140761 1 49 theme fibrosis 285:292 arg1 patients 294:301 cystic fibrosis patients 278:301 cystic fibrosis patients 278:301 The structure of carbohydrate units of bronchial-mucus glycoproteins obtained from cystic fibrosis patients was investigated by 500-MHz 1H-NMR spectroscopy and methylation analysis. 7140761 2 50 theme borohydride 430:440 arg1 degradation 442:452 alkaline borohydride degradation 421:452 alkaline borohydride degradation 421:452 To that purpose, the mucin was subjected to alkaline borohydride degradation. 7140761 0 51 theme bronchial-mucus 82:96 arg1 glycoproteins 98:110 bronchial-mucus glycoproteins 82:110 bronchial-mucus glycoproteins of patients suffering from cystic fibrosis 82:153 Primary-structure determination of fourteen neutral oligosaccharides derived from bronchial-mucus glycoproteins of patients suffering from cystic fibrosis, employing 500-MHz 1H-NMR spectroscopy. 7140761 2 52 theme alkaline 421:428 arg1 degradation 442:452 alkaline borohydride degradation 421:452 alkaline borohydride degradation 421:452 To that purpose, the mucin was subjected to alkaline borohydride degradation. 1488058 5 0 dep 22 901:902 arg1 to 898:899 to 898:899 to 898:899 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues were found. 1488058 12 1 theme 2-linked 2388:2395 arg1 fucose 2397:2402 alpha 2-linked fucose 2382:2402 alpha 2-linked fucose 2382:2402 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 10 2 from chains 1897:1902 arg1 present 1858:1864 present 1858:1864 present 1858:1864 Increasing numbers of the repeating sequence shown in the oligosaccharide below is present in the higher molecular weight chains. 1488058 9 3 theme molecular 1641:1649 arg1 chains 1674:1679 even higher molecular weight oligosaccharide chains 1629:1679 even higher molecular weight oligosaccharide chains with analogous branched structures 1629:1714 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 12 4 theme structure 2329:2337 arg1 variations 2292:2301 variations 2292:2301 variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point 2292:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 11 5 theme chains 2032:2037 arg1 branching 1997:2005 the extensive branching 1983:2005 the extensive branching of these oligosaccharide chains 1983:2037 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 11 6 theme oligosaccharide 2016:2030 arg1 chains 2032:2037 these oligosaccharide chains 2010:2037 these oligosaccharide chains 2010:2037 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 9 7 theme oligosaccharide 1658:1672 arg1 chains 1674:1679 even higher molecular weight oligosaccharide chains 1629:1679 even higher molecular weight oligosaccharide chains with analogous branched structures 1629:1714 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 8 8 link 6-linked 1388:1395 arg1 residue 1404:1410 the beta 6-linked G1cNAc residue 1379:1410 the beta 6-linked G1cNAc residue 1379:1410 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 8 9 link 3-linked 1337:1344 arg1 G1cNAc 1346:1351 the beta 3-linked G1cNAc 1328:1351 the beta 3-linked G1cNAc 1328:1351 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 11 10 theme respiratory 2141:2151 arg1 glycoproteins 2159:2171 human and swine respiratory mucin glycoproteins 2125:2171 human and swine respiratory mucin glycoproteins 2125:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 8 11 theme oligosaccharide 1273:1287 arg1 chains 1289:1294 oligosaccharide chains 1273:1294 oligosaccharide chains 1273:1294 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 3 12 theme oligosaccharides 634:649 arg1 structures 607:616 The structures 603:616 The structures of the purified oligosaccharides 603:649 The structures of the purified oligosaccharides were determined by methylation analysis, sequential glycosidase digestion and 'H-NMR spectroscopy. 1488058 11 13 theme swine 2135:2139 arg1 glycoproteins 2159:2171 human and swine respiratory mucin glycoproteins 2125:2171 human and swine respiratory mucin glycoproteins 2125:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 9 14 theme branched 1696:1703 arg1 structures 1705:1714 analogous branched structures 1686:1714 analogous branched structures 1686:1714 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 12 15 theme chain 2240:2244 arg1 concentrations 2201:2214 the relative concentrations 2188:2214 the relative concentrations of each oligosaccharide chain 2188:2244 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 7 16 theme group 1141:1145 arg1 A 1147:1147 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A 1085:1147 A 1147:1147 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 2 17 attach isolated 307:314 arg1 mucin 321:325 mucin 321:325 mucin obtained from a patient with A blood group determinant 321:380 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 2 17 attach isolated 307:314 arg2 fraction 294:301 A neutral oligosaccharide alditol fraction 260:301 A neutral oligosaccharide alditol fraction 260:301 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 8 18 theme alpha 1458:1462 arg1 structure 1507:1515 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 11 19 from observations 1967:1978 arg1 branching 1997:2005 the extensive branching 1983:2005 the extensive branching of these oligosaccharide chains 1983:2037 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 11 20 with conjunction 1938:1948 arg1 observations 1967:1978 our earlier observations 1955:1978 our earlier observations on the extensive branching of these oligosaccharide chains 1955:2037 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 3 21 theme methylation 670:680 arg1 analysis 682:689 methylation analysis 670:689 methylation analysis 670:689 The structures of the purified oligosaccharides were determined by methylation analysis, sequential glycosidase digestion and 'H-NMR spectroscopy. 1488058 2 22 with filtration 482:491 arg1 systems 594:600 isocratic solvent systems 576:600 isocratic solvent systems 576:600 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 2 22 with filtration 482:491 arg1 gradient 563:570 gradient 563:570 gradient 563:570 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 1 23 theme alkaline 238:245 arg1 borohydride 247:257 alkaline borohydride 238:257 alkaline borohydride 238:257 Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. 1488058 11 24 theme structures 2105:2114 arg1 range 2080:2084 the enormous range 2067:2084 the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins 2067:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 2 25 from chromatography 543:556 arg1 columns 507:513 BioGel P-6 columns 496:513 BioGel P-6 columns 496:513 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 11 26 from data 1930:1933 arg1 conjunction 1938:1948 conjunction 1938:1948 conjunction with our earlier observations on the extensive branching of these oligosaccharide chains 1938:2037 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 7 27 dep alpha 1154:1158 arg1 beta 1183:1186 Ga1 beta 4 1179:1188 Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4 1150:1188 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 12 28 from point 2460:2464 arg1 residue 2437:2443 the beta 3/4 linked galactose residue 2407:2443 the beta 3/4 linked galactose residue at each branch point 2407:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 10 29 theme sequence 1811:1818 arg1 numbers 1786:1792 Increasing numbers 1775:1792 Increasing numbers of the repeating sequence 1775:1818 Increasing numbers of the repeating sequence shown in the oligosaccharide below is present in the higher molecular weight chains. 1488058 7 30 theme group 1100:1104 arg1 beta 1124:1127 Fuc alpha 2Ga1 beta 4 1109:1129 Fuc alpha 2Ga1 beta 4 1109:1129 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 7 30 theme group 1100:1104 arg1 H 1106:1106 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A 1085:1147 H 1106:1106 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 6 31 theme larger 1003:1008 arg1 chains 1010:1015 larger chains 1003:1015 larger chains 1003:1015 Many of the oligosaccharides are related and appear to be precursors of larger chains. 1488058 9 32 theme human 1736:1740 arg1 glycoproteins 1760:1772 some human respiratory mucin glycoproteins 1731:1772 some human respiratory mucin glycoproteins 1731:1772 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 5 33 contain contain 883:889 arg2 residues 910:917 from 3 to 22 sugar residues 891:917 from 3 to 22 sugar residues 891:917 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues were found. 1488058 5 33 contain contain 883:889 arg1 structures 867:876 discrete branched oligosaccharide structures 833:876 discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues 833:917 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues were found. 1488058 8 34 theme beta 1332:1335 arg1 G1cNAc 1346:1351 the beta 3-linked G1cNAc 1328:1351 the beta 3-linked G1cNAc 1328:1351 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 7 35 theme 2Ga1 1119:1122 arg1 beta 1124:1127 Fuc alpha 2Ga1 beta 4 1109:1129 Fuc alpha 2Ga1 beta 4 1109:1129 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 7 35 theme 2Ga1 1119:1122 arg1 H 1106:1106 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A 1085:1147 H 1106:1106 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 3 36 theme glycosidase 703:713 arg1 digestion 715:723 sequential glycosidase digestion 692:723 sequential glycosidase digestion 692:723 The structures of the purified oligosaccharides were determined by methylation analysis, sequential glycosidase digestion and 'H-NMR spectroscopy. 1488058 7 37 theme terminal 1085:1092 arg1 beta 1124:1127 Fuc alpha 2Ga1 beta 4 1109:1129 Fuc alpha 2Ga1 beta 4 1109:1129 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 7 37 theme terminal 1085:1092 arg1 H 1106:1106 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A 1085:1147 H 1106:1106 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 1 38 theme cystic 149:154 arg1 fibrosis 156:163 cystic fibrosis 149:163 cystic fibrosis 149:163 Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. 1488058 9 39 theme mucin 1754:1758 arg1 glycoproteins 1760:1772 some human respiratory mucin glycoproteins 1731:1772 some human respiratory mucin glycoproteins 1731:1772 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 5 40 theme discrete 833:840 arg1 structures 867:876 discrete branched oligosaccharide structures 833:876 discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues 833:917 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues were found. 1488058 2 41 theme oligosaccharide 270:284 arg1 fraction 294:301 A neutral oligosaccharide alditol fraction 260:301 A neutral oligosaccharide alditol fraction 260:301 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 2 42 theme liquid 536:541 arg1 chromatography 543:556 high performance liquid chromatography 519:556 high performance liquid chromatography with gradient and isocratic solvent systems 519:600 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 0 43 from structures 17:26 arg1 glycoproteins 77:89 human trachea mucin glycoproteins 57:89 human trachea mucin glycoproteins 57:89 Quantitation and structures of oligosaccharide chains in human trachea mucin glycoproteins. 1488058 11 44 theme oligosaccharide 2089:2103 arg1 structures 2105:2114 oligosaccharide structures 2089:2114 oligosaccharide structures found in human and swine respiratory mucin glycoproteins 2089:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 8 45 theme branch 1356:1361 arg1 points 1363:1368 branch points 1356:1368 branch points 1356:1368 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 7 46 theme chain 1237:1241 arg1 elongation 1243:1252 chain elongation 1237:1252 chain elongation 1237:1252 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 11 47 theme human 2125:2129 arg1 glycoproteins 2159:2171 human and swine respiratory mucin glycoproteins 2125:2171 human and swine respiratory mucin glycoproteins 2125:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 9 48 from present 1720:1726 arg1 glycoproteins 1760:1772 some human respiratory mucin glycoproteins 1731:1772 some human respiratory mucin glycoproteins 1731:1772 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 2 49 theme solvent 586:592 arg1 systems 594:600 isocratic solvent systems 576:600 isocratic solvent systems 576:600 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 8 50 theme G1cNAc 1493:1498 arg1 structure 1507:1515 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 7 51 theme predominant 1022:1032 arg1 oligosaccharides 1043:1058 The predominant branched oligosaccharides 1018:1058 The predominant branched oligosaccharides which accumulate 1018:1075 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 2 52 with patient 343:349 arg1 determinant 370:380 A blood group determinant 356:380 A blood group determinant 356:380 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 7 53 dep H 1106:1106 arg1 alpha 1154:1158 Fuc alpha 2 1150:1160 Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4 1150:1188 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 7 53 dep H 1106:1106 arg1 alpha 1169:1173 Ga1NAc alpha 3 1162:1175 Ga1NAc alpha 3 1162:1175 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 13 54 theme respiratory 2544:2554 arg1 mucins 2556:2561 these respiratory mucins 2538:2561 these respiratory mucins 2538:2561 These chains accumulate and are found in the highest concentrations in these respiratory mucins. 1488058 0 55 theme chains 47:52 arg1 structures 17:26 structures 17:26 structures 17:26 Quantitation and structures of oligosaccharide chains in human trachea mucin glycoproteins. 1488058 0 55 theme chains 47:52 arg1 Quantitation 0:11 Quantitation 0:11 Quantitation 0:11 Quantitation and structures of oligosaccharide chains in human trachea mucin glycoproteins. 1488058 2 56 theme BioGel 496:501 arg1 columns 507:513 BioGel P-6 columns 496:513 BioGel P-6 columns 496:513 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 12 57 theme branched 2315:2322 arg1 structure 2329:2337 a common branched core structure 2306:2337 a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point 2306:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 8 58 theme 6-linked 1388:1395 arg1 residue 1404:1410 the beta 6-linked G1cNAc residue 1379:1410 the beta 6-linked G1cNAc residue 1379:1410 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 2 59 theme individual 422:431 arg1 chains 449:454 individual oligosaccharide chains 422:454 individual oligosaccharide chains 422:454 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 1 60 with patients 135:142 arg1 fibrosis 156:163 cystic fibrosis 149:163 cystic fibrosis 149:163 Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. 1488058 1 61 theme respiratory 98:108 arg1 glycoproteins 116:128 Human respiratory mucin glycoproteins 92:128 Human respiratory mucin glycoproteins from patients with cystic fibrosis 92:163 Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. 1488058 10 62 theme higher 1873:1878 arg1 chains 1897:1902 the higher molecular weight chains 1869:1902 the higher molecular weight chains 1869:1902 Increasing numbers of the repeating sequence shown in the oligosaccharide below is present in the higher molecular weight chains. 1488058 8 63 with individuals 1520:1530 arg1 determinant 1551:1561 A blood group determinant 1537:1561 A blood group determinant 1537:1561 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 5 64 theme sugar 904:908 arg1 residues 910:917 from 3 to 22 sugar residues 891:917 from 3 to 22 sugar residues 891:917 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues were found. 1488058 6 65 theme oligosaccharides 943:958 arg1 Many 931:934 Many 931:934 Many 931:934 Many of the oligosaccharides are related and appear to be precursors of larger chains. 1488058 6 65 theme oligosaccharides 943:958 arg1 oligosaccharides 943:958 the oligosaccharides 939:958 the oligosaccharides 939:958 Many of the oligosaccharides are related and appear to be precursors of larger chains. 1488058 11 66 dep [formula 1905:1912 arg1 see 1915:1917 see 1915:1917 see text 1915:1922 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 11 66 dep [formula 1905:1912 arg1 helps 2039:2043 helps 2039:2043 helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins 2039:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 10 67 from present 1858:1864 arg1 chains 1897:1902 the higher molecular weight chains 1869:1902 the higher molecular weight chains 1869:1902 Increasing numbers of the repeating sequence shown in the oligosaccharide below is present in the higher molecular weight chains. 1488058 2 68 theme high 519:522 arg1 chromatography 543:556 high performance liquid chromatography 519:556 high performance liquid chromatography with gradient and isocratic solvent systems 519:600 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 8 69 theme blood 1539:1543 arg1 determinant 1551:1561 A blood group determinant 1537:1561 A blood group determinant 1537:1561 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 3 70 theme H-NMR 730:734 arg1 spectroscopy 736:747 'H-NMR spectroscopy 729:747 'H-NMR spectroscopy 729:747 The structures of the purified oligosaccharides were determined by methylation analysis, sequential glycosidase digestion and 'H-NMR spectroscopy. 1488058 7 71 theme Ga1 1179:1181 arg1 beta 1183:1186 Ga1 beta 4 1179:1188 Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4 1150:1188 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 0 72 theme oligosaccharide 31:45 arg1 chains 47:52 oligosaccharide chains 31:52 oligosaccharide chains 31:52 Quantitation and structures of oligosaccharide chains in human trachea mucin glycoproteins. 1488058 0 73 theme trachea 63:69 arg1 glycoproteins 77:89 human trachea mucin glycoproteins 57:89 human trachea mucin glycoproteins 57:89 Quantitation and structures of oligosaccharide chains in human trachea mucin glycoproteins. 1488058 8 74 theme side 1435:1438 arg1 chains 1440:1445 short side chains 1429:1445 short side chains 1429:1445 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 11 75 theme mucin 2153:2157 arg1 glycoproteins 2159:2171 human and swine respiratory mucin glycoproteins 2125:2171 human and swine respiratory mucin glycoproteins 2125:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 1 76 with treatment 223:231 arg1 borohydride 247:257 alkaline borohydride 238:257 alkaline borohydride 238:257 Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. 1488058 9 77 theme current 1592:1598 arg1 studies 1600:1606 the current studies 1588:1606 the current studies 1588:1606 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 12 78 link 2-linked 2388:2395 arg1 fucose 2397:2402 alpha 2-linked fucose 2382:2402 alpha 2-linked fucose 2382:2402 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 2 79 theme blood 358:362 arg1 determinant 370:380 A blood group determinant 356:380 A blood group determinant 356:380 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 12 80 theme linked 2420:2425 arg1 residue 2437:2443 the beta 3/4 linked galactose residue 2407:2443 the beta 3/4 linked galactose residue at each branch point 2407:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 7 81 contain contain 1077:1083 arg2 determinants 1191:1202 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants 1085:1202 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation 1085:1252 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 7 81 contain contain 1077:1083 arg1 oligosaccharides 1043:1058 The predominant branched oligosaccharides 1018:1058 The predominant branched oligosaccharides which accumulate 1018:1075 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 10 82 theme weight 1890:1895 arg1 chains 1897:1902 the higher molecular weight chains 1869:1902 the higher molecular weight chains 1869:1902 Increasing numbers of the repeating sequence shown in the oligosaccharide below is present in the higher molecular weight chains. 1488058 8 83 theme Fuc 1454:1456 arg1 alpha 1458:1462 Fuc alpha 2 1454:1464 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 8 83 theme Fuc 1454:1456 arg1 alpha 1473:1477 Ga1NAc alpha 3 1466:1479 Ga1NAc alpha 3 1466:1479 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 8 84 dep occurs 1318:1323 arg1 whereas 1371:1377 whereas 1371:1377 whereas 1371:1377 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 7 85 theme Ga1NAc 1162:1167 arg1 alpha 1154:1158 Fuc alpha 2 1150:1160 Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4 1150:1188 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 7 85 theme Ga1NAc 1162:1167 arg1 alpha 1169:1173 Ga1NAc alpha 3 1162:1175 Ga1NAc alpha 3 1162:1175 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 8 86 theme beta 1486:1489 arg1 structure 1507:1515 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 9 87 theme higher 1634:1639 arg1 chains 1674:1679 even higher molecular weight oligosaccharide chains 1629:1679 even higher molecular weight oligosaccharide chains with analogous branched structures 1629:1714 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 13 88 theme highest 2512:2518 arg1 concentrations 2520:2533 the highest concentrations 2508:2533 the highest concentrations in these respiratory mucins 2508:2561 These chains accumulate and are found in the highest concentrations in these respiratory mucins. 1488058 12 89 theme oligosaccharide 2224:2238 arg1 chain 2240:2244 each oligosaccharide chain 2219:2244 each oligosaccharide chain 2219:2244 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 10 90 theme Increasing 1775:1784 arg1 numbers 1786:1792 Increasing numbers 1775:1792 Increasing numbers of the repeating sequence 1775:1818 Increasing numbers of the repeating sequence shown in the oligosaccharide below is present in the higher molecular weight chains. 1488058 10 91 theme repeating 1801:1809 arg1 sequence 1811:1818 the repeating sequence 1797:1818 the repeating sequence 1797:1818 Increasing numbers of the repeating sequence shown in the oligosaccharide below is present in the higher molecular weight chains. 1488058 9 92 theme weight 1651:1656 arg1 chains 1674:1679 even higher molecular weight oligosaccharide chains 1629:1679 even higher molecular weight oligosaccharide chains with analogous branched structures 1629:1714 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 12 93 theme beta 2411:2414 arg1 residue 2437:2443 the beta 3/4 linked galactose residue 2407:2443 the beta 3/4 linked galactose residue at each branch point 2407:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 7 94 theme Fuc 1150:1152 arg1 alpha 1154:1158 Fuc alpha 2 1150:1160 Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4 1150:1188 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 7 94 theme Fuc 1150:1152 arg1 alpha 1169:1173 Ga1NAc alpha 3 1162:1175 Ga1NAc alpha 3 1162:1175 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 12 95 theme galactose 2427:2435 arg1 residue 2437:2443 the beta 3/4 linked galactose residue 2407:2443 the beta 3/4 linked galactose residue at each branch point 2407:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 1 96 theme oligosaccharide 183:197 arg1 chains 199:204 oligosaccharide chains 183:204 oligosaccharide chains 183:204 Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. 1488058 2 97 from chromatography 385:398 arg1 DEAE-cellulose 403:416 DEAE-cellulose 403:416 DEAE-cellulose 403:416 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 12 98 link linked 2420:2425 arg1 residue 2437:2443 the beta 3/4 linked galactose residue 2407:2443 the beta 3/4 linked galactose residue at each branch point 2407:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 5 99 theme oligosaccharide 851:865 arg1 structures 867:876 discrete branched oligosaccharide structures 833:876 discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues 833:917 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues were found. 1488058 7 100 theme A 1147:1147 arg1 determinants 1191:1202 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants 1085:1202 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation 1085:1252 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 3 101 theme purified 625:632 arg1 oligosaccharides 634:649 the purified oligosaccharides 621:649 the purified oligosaccharides 621:649 The structures of the purified oligosaccharides were determined by methylation analysis, sequential glycosidase digestion and 'H-NMR spectroscopy. 1488058 9 102 theme analogous 1686:1694 arg1 structures 1705:1714 analogous branched structures 1686:1714 analogous branched structures 1686:1714 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 7 103 theme blood 1135:1139 arg1 A 1147:1147 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A 1085:1147 A 1147:1147 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 12 104 theme alpha 2382:2386 arg1 fucose 2397:2402 alpha 2-linked fucose 2382:2402 alpha 2-linked fucose 2382:2402 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 7 105 theme branched 1034:1041 arg1 oligosaccharides 1043:1058 The predominant branched oligosaccharides 1018:1058 The predominant branched oligosaccharides which accumulate 1018:1075 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 8 106 theme chains 1289:1294 arg1 elongation 1259:1268 The elongation 1255:1268 The elongation of oligosaccharide chains in respiratory mucins 1255:1316 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 2 107 theme neutral 262:268 arg1 fraction 294:301 A neutral oligosaccharide alditol fraction 260:301 A neutral oligosaccharide alditol fraction 260:301 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 8 108 theme Ga1NAc 1466:1471 arg1 alpha 1458:1462 Fuc alpha 2 1454:1464 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 8 108 theme Ga1NAc 1466:1471 arg1 alpha 1473:1477 Ga1NAc alpha 3 1466:1479 Ga1NAc alpha 3 1466:1479 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 8 109 theme respiratory 1299:1309 arg1 mucins 1311:1316 respiratory mucins 1299:1316 respiratory mucins 1299:1316 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 11 110 theme extensive 1987:1995 arg1 branching 1997:2005 the extensive branching 1983:2005 the extensive branching of these oligosaccharide chains 1983:2037 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 7 111 theme Fuc 1109:1111 arg1 beta 1124:1127 Fuc alpha 2Ga1 beta 4 1109:1129 Fuc alpha 2Ga1 beta 4 1109:1129 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 7 111 theme Fuc 1109:1111 arg1 H 1106:1106 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A 1085:1147 H 1106:1106 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 0 112 from Quantitation 0:11 arg1 glycoproteins 77:89 human trachea mucin glycoproteins 57:89 human trachea mucin glycoproteins 57:89 Quantitation and structures of oligosaccharide chains in human trachea mucin glycoproteins. 1488058 6 113 theme chains 1010:1015 arg1 precursors 989:998 precursors 989:998 precursors of larger chains 989:1015 Many of the oligosaccharides are related and appear to be precursors of larger chains. 1488058 11 114 theme enormous 2071:2078 arg1 range 2080:2084 the enormous range 2067:2084 the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins 2067:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 7 115 theme alpha 1113:1117 arg1 beta 1124:1127 Fuc alpha 2Ga1 beta 4 1109:1129 Fuc alpha 2Ga1 beta 4 1109:1129 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 7 115 theme alpha 1113:1117 arg1 H 1106:1106 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A 1085:1147 H 1106:1106 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 3 116 theme sequential 692:701 arg1 digestion 715:723 sequential glycosidase digestion 692:723 sequential glycosidase digestion 692:723 The structures of the purified oligosaccharides were determined by methylation analysis, sequential glycosidase digestion and 'H-NMR spectroscopy. 1488058 7 117 theme H 1106:1106 arg1 determinants 1191:1202 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants 1085:1202 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation 1085:1252 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 9 118 located present 1720:1726 arg2 chains 1674:1679 even higher molecular weight oligosaccharide chains 1629:1679 even higher molecular weight oligosaccharide chains with analogous branched structures 1629:1714 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 9 118 located present 1720:1726 arg1 glycoproteins 1760:1772 some human respiratory mucin glycoproteins 1731:1772 some human respiratory mucin glycoproteins 1731:1772 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 9 119 theme respiratory 1742:1752 arg1 glycoproteins 1760:1772 some human respiratory mucin glycoproteins 1731:1772 some human respiratory mucin glycoproteins 1731:1772 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 8 120 theme Ga1 1482:1484 arg1 structure 1507:1515 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 4 121 theme compositional 793:805 arg1 analysis 807:814 compositional analysis 793:814 compositional analysis 793:814 The amount of each chain was determined by compositional analysis. 1488058 9 122 attach present 1720:1726 arg2 chains 1674:1679 even higher molecular weight oligosaccharide chains 1629:1679 even higher molecular weight oligosaccharide chains with analogous branched structures 1629:1714 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 9 122 attach present 1720:1726 arg1 glycoproteins 1760:1772 some human respiratory mucin glycoproteins 1731:1772 some human respiratory mucin glycoproteins 1731:1772 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 0 123 theme mucin 71:75 arg1 glycoproteins 77:89 human trachea mucin glycoproteins 57:89 human trachea mucin glycoproteins 57:89 Quantitation and structures of oligosaccharide chains in human trachea mucin glycoproteins. 1488058 2 124 theme alditol 286:292 arg1 fraction 294:301 A neutral oligosaccharide alditol fraction 260:301 A neutral oligosaccharide alditol fraction 260:301 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 7 125 theme blood 1094:1098 arg1 beta 1124:1127 Fuc alpha 2Ga1 beta 4 1109:1129 Fuc alpha 2Ga1 beta 4 1109:1129 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 7 125 theme blood 1094:1098 arg1 H 1106:1106 terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A 1085:1147 H 1106:1106 The predominant branched oligosaccharides which accumulate contain terminal blood group H (Fuc alpha 2Ga1 beta 4) or blood group A (Fuc alpha 2(Ga1NAc alpha 3) (Ga1 beta 4) determinants which stop further branching and chain elongation. 1488058 13 126 located found 2499:2503 arg1 concentrations 2520:2533 the highest concentrations 2508:2533 the highest concentrations in these respiratory mucins 2508:2561 These chains accumulate and are found in the highest concentrations in these respiratory mucins. 1488058 13 126 located found 2499:2503 arg2 chains 2473:2478 These chains 2467:2478 These chains 2467:2478 These chains accumulate and are found in the highest concentrations in these respiratory mucins. 1488058 2 127 from filtration 482:491 arg1 columns 507:513 BioGel P-6 columns 496:513 BioGel P-6 columns 496:513 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 8 128 theme 3-linked 1337:1344 arg1 G1cNAc 1346:1351 the beta 3-linked G1cNAc 1328:1351 the beta 3-linked G1cNAc 1328:1351 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 5 129 theme branched 842:849 arg1 structures 867:876 discrete branched oligosaccharide structures 833:876 discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues 833:917 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues were found. 1488058 2 130 theme performance 524:534 arg1 chromatography 543:556 high performance liquid chromatography 519:556 high performance liquid chromatography with gradient and isocratic solvent systems 519:600 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 8 131 theme beta 1500:1503 arg1 structure 1507:1515 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure 1452:1515 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 4 132 theme chain 769:773 arg1 chain 769:773 each chain 764:773 each chain 764:773 The amount of each chain was determined by compositional analysis. 1488058 4 132 theme chain 769:773 arg1 amount 754:759 The amount 750:759 The amount of each chain 750:773 The amount of each chain was determined by compositional analysis. 1488058 2 133 theme isocratic 576:584 arg1 systems 594:600 isocratic solvent systems 576:600 isocratic solvent systems 576:600 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 12 134 theme common 2308:2313 arg1 structure 2329:2337 a common branched core structure 2306:2337 a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point 2306:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 1 135 gly glycoproteins 116:128 arg1 glycoproteins 116:128 Human respiratory mucin glycoproteins 92:128 Human respiratory mucin glycoproteins from patients with cystic fibrosis 92:163 Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. 1488058 2 136 with chromatography 543:556 arg1 systems 594:600 isocratic solvent systems 576:600 isocratic solvent systems 576:600 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 2 136 with chromatography 543:556 arg1 gradient 563:570 gradient 563:570 gradient 563:570 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 0 137 gly glycoproteins 77:89 arg1 glycoproteins 77:89 human trachea mucin glycoproteins 57:89 human trachea mucin glycoproteins 57:89 Quantitation and structures of oligosaccharide chains in human trachea mucin glycoproteins. 1488058 11 138 gly glycoproteins 2159:2171 arg1 glycoproteins 2159:2171 human and swine respiratory mucin glycoproteins 2125:2171 human and swine respiratory mucin glycoproteins 2125:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 13 139 from concentrations 2520:2533 arg1 mucins 2556:2561 these respiratory mucins 2538:2561 these respiratory mucins 2538:2561 These chains accumulate and are found in the highest concentrations in these respiratory mucins. 1488058 12 140 theme core 2324:2327 arg1 structure 2329:2337 a common branched core structure 2306:2337 a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point 2306:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 2 141 theme oligosaccharide 433:447 arg1 chains 449:454 individual oligosaccharide chains 422:454 individual oligosaccharide chains 422:454 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 1 142 theme Human 92:96 arg1 glycoproteins 116:128 Human respiratory mucin glycoproteins 92:128 Human respiratory mucin glycoproteins from patients with cystic fibrosis 92:163 Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. 1488058 8 143 theme beta 1383:1386 arg1 residue 1404:1410 the beta 6-linked G1cNAc residue 1379:1410 the beta 6-linked G1cNAc residue 1379:1410 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 12 144 theme relative 2192:2199 arg1 concentrations 2201:2214 the relative concentrations 2188:2214 the relative concentrations of each oligosaccharide chain 2188:2244 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 1 145 from patients 135:142 arg1 glycoproteins 116:128 Human respiratory mucin glycoproteins 92:128 Human respiratory mucin glycoproteins from patients with cystic fibrosis 92:163 Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. 1488058 1 146 theme mucin 110:114 arg1 glycoproteins 116:128 Human respiratory mucin glycoproteins 92:128 Human respiratory mucin glycoproteins from patients with cystic fibrosis 92:163 Human respiratory mucin glycoproteins from patients with cystic fibrosis were purified and oligosaccharide chains were released by treatment with alkaline borohydride. 1488058 11 147 theme earlier 1959:1965 arg1 observations 1967:1978 our earlier observations 1955:1978 our earlier observations on the extensive branching of these oligosaccharide chains 1955:2037 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 2 148 theme gel 478:480 arg1 filtration 482:491 gel filtration 478:491 gel filtration on BioGel P-6 columns 478:513 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 8 149 theme group 1545:1549 arg1 determinant 1551:1561 A blood group determinant 1537:1561 A blood group determinant 1537:1561 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 10 150 theme molecular 1880:1888 arg1 chains 1897:1902 the higher molecular weight chains 1869:1902 the higher molecular weight chains 1869:1902 Increasing numbers of the repeating sequence shown in the oligosaccharide below is present in the higher molecular weight chains. 1488058 8 151 theme G1cNAc 1397:1402 arg1 residue 1404:1410 the beta 6-linked G1cNAc residue 1379:1410 the beta 6-linked G1cNAc residue 1379:1410 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 5 152 theme structures 867:876 arg1 array 824:828 A wide array 817:828 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues 817:917 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues were found. 1488058 12 153 theme branch 2453:2458 arg1 point 2460:2464 each branch point 2448:2464 each branch point 2448:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 12 154 theme concentrations 2201:2214 arg1 Comparison 2174:2183 Comparison 2174:2183 Comparison of the relative concentrations of each oligosaccharide chain 2174:2244 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 0 155 theme human 57:61 arg1 glycoproteins 77:89 human trachea mucin glycoproteins 57:89 human trachea mucin glycoproteins 57:89 Quantitation and structures of oligosaccharide chains in human trachea mucin glycoproteins. 1488058 2 156 theme P-6 503:505 arg1 columns 507:513 BioGel P-6 columns 496:513 BioGel P-6 columns 496:513 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 8 157 theme short 1429:1433 arg1 chains 1440:1445 short side chains 1429:1445 short side chains 1429:1445 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 12 158 theme fucose 2397:2402 arg1 addition 2370:2377 the addition 2366:2377 the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point 2366:2464 Comparison of the relative concentrations of each oligosaccharide chain suggest that these oligosaccharides represent variations of a common branched core structure which may be terminated by the addition of alpha 2-linked fucose to the beta 3/4 linked galactose residue at each branch point. 1488058 2 159 theme group 364:368 arg1 determinant 370:380 A blood group determinant 356:380 A blood group determinant 356:380 A neutral oligosaccharide alditol fraction was isolated from mucin obtained from a patient with A blood group determinant by chromatography on DEAE-cellulose and individual oligosaccharide chains were then isolated by gel filtration on BioGel P-6 columns and high performance liquid chromatography with gradient and isocratic solvent systems. 1488058 8 160 from elongation 1259:1268 arg1 mucins 1311:1316 respiratory mucins 1299:1316 respiratory mucins 1299:1316 The elongation of oligosaccharide chains in respiratory mucins occurs on the beta 3-linked G1cNAc at branch points, whereas the beta 6-linked G1cNAc residue ultimately forms short side chains with a Fuc alpha 2(Ga1NAc alpha 3) Ga1 beta 4 G1cNAc beta 6 structure in individuals with A blood group determinant. 1488058 5 161 theme wide 819:822 arg1 array 824:828 A wide array 817:828 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues 817:917 A wide array of discrete branched oligosaccharide structures that contain from 3 to 22 sugar residues were found. 1488058 11 162 located found 2116:2120 arg2 structures 2105:2114 oligosaccharide structures 2089:2114 oligosaccharide structures found in human and swine respiratory mucin glycoproteins 2089:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 11 162 located found 2116:2120 arg1 glycoproteins 2159:2171 human and swine respiratory mucin glycoproteins 2125:2171 human and swine respiratory mucin glycoproteins 2125:2171 [formula: see text] This data in conjunction with our earlier observations on the extensive branching of these oligosaccharide chains helps to define and explain the enormous range of oligosaccharide structures found in human and swine respiratory mucin glycoproteins. 1488058 9 163 gly glycoproteins 1760:1772 arg1 glycoproteins 1760:1772 some human respiratory mucin glycoproteins 1731:1772 some human respiratory mucin glycoproteins 1731:1772 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 9 164 with chains 1674:1679 arg1 structures 1705:1714 analogous branched structures 1686:1714 analogous branched structures 1686:1714 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 1488058 9 165 from glycoproteins 1760:1772 arg1 present 1720:1726 present 1720:1726 present 1720:1726 The results obtained in the current studies further suggest that even higher molecular weight oligosaccharide chains with analogous branched structures are present in some human respiratory mucin glycoproteins. 32639750 4 0 theme classes 998:1004 arg1 construction 976:987 library construction 968:987 library construction of other classes of compounds 968:1017 The general approach appears applicable to library construction of other classes of compounds. 32639750 1 1 theme milk 327:330 arg1 oligosaccharides 332:347 74 human milk oligosaccharides 318:347 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 318:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 1 1 theme milk 327:330 arg1 HMOs 350:353 HMOs 350:353 HMOs 350:353 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 2 2 theme distinguishable 722:736 arg1 glycans 738:744 all distinguishable glycans 718:744 all distinguishable glycans in milk 718:752 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 6 3 theme milk 1308:1311 arg1 reanalysis 1288:1297 reanalysis 1288:1297 reanalysis of human milk 1288:1311 This new method led to the identification of another 145 oligosaccharides, including an additional 80 HMOs from reanalysis of human milk. 32639750 3 4 theme NIST 898:901 arg1 Library 916:922 the NIST 17 Tandem MS Library 894:922 the NIST 17 Tandem MS Library 894:922 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 0 5 theme Oligosaccharides 59:74 arg1 Library 43:49 a Mass Spectral Library 27:49 a Mass Spectral Library of Milk Oligosaccharides 27:74 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 1 6 theme oligosaccharides 332:347 arg1 library 307:313 a previously reported tandem mass spectral library 264:313 a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 264:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 2 7 theme oligosaccharides 590:605 arg1 coverage 573:580 the coverage 569:580 the coverage of milk oligosaccharides 569:605 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 1 8 theme analysis 439:446 arg1 results 369:375 results 369:375 results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 369:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 1 9 attach derived 356:362 arg1 results 369:375 results 369:375 results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 369:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 1 9 attach derived 356:362 arg2 HMOs 350:353 HMOs 350:353 HMOs 350:353 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 1 9 attach derived 356:362 arg2 oligosaccharides 332:347 74 human milk oligosaccharides 318:347 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 318:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 3 10 theme spectra 883:889 arg1 search 857:862 the hybrid search 846:862 the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library 846:922 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 0 11 theme Hybrid-Search-Based 84:102 arg1 Method 118:123 a Hybrid-Search-Based Bootstrapping Method 82:123 a Hybrid-Search-Based Bootstrapping Method 82:123 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 8 12 from limitations 1489:1499 arg1 interpretation 1521:1534 the interpretation 1517:1534 the interpretation of spectra of unknown oligosaccharides 1517:1573 We also provide suggestions to overcome several limitations and pitfalls in the interpretation of spectra of unknown oligosaccharides. 32639750 2 13 theme milk 585:588 arg1 oligosaccharides 590:605 milk oligosaccharides 585:605 milk oligosaccharides 585:605 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 6 14 theme new 1181:1183 arg1 method 1185:1190 This new method 1176:1190 This new method 1176:1190 This new method led to the identification of another 145 oligosaccharides, including an additional 80 HMOs from reanalysis of human milk. 32639750 2 15 theme " 504:504 arg1 method 521:526 a hybrid search "bootstrap" identification method 478:526 a hybrid search "bootstrap" identification method 478:526 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 5 16 theme mammals 1110:1116 arg1 buffalo 1143:1149 Asian buffalo 1137:1149 Asian buffalo 1137:1149 The coverage of oligosaccharides was significantly extended using milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat. 32639750 5 16 theme mammals 1110:1116 arg1 goat 1170:1173 goat 1170:1173 goat 1170:1173 The coverage of oligosaccharides was significantly extended using milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat. 32639750 5 16 theme mammals 1110:1116 arg1 mammals 1110:1116 mammals 1110:1116 mammals 1110:1116 The coverage of oligosaccharides was significantly extended using milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat. 32639750 5 16 theme mammals 1110:1116 arg1 bovine 1129:1134 bovine 1129:1134 bovine 1129:1134 The coverage of oligosaccharides was significantly extended using milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat. 32639750 5 16 theme mammals 1110:1116 arg1 lion 1160:1163 African lion 1152:1163 African lion 1152:1163 The coverage of oligosaccharides was significantly extended using milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat. 32639750 5 16 theme mammals 1110:1116 arg1 variety 1099:1105 a variety 1097:1105 a variety 1097:1105 The coverage of oligosaccharides was significantly extended using milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat. 32639750 6 17 theme additional 1264:1273 arg1 HMOs 1278:1281 an additional 80 HMOs 1261:1281 an additional 80 HMOs from reanalysis of human milk 1261:1311 This new method led to the identification of another 145 oligosaccharides, including an additional 80 HMOs from reanalysis of human milk. 32639750 1 18 theme HMOs 451:454 arg1 analysis 439:446 comprehensive structural analysis 414:446 comprehensive structural analysis of HMOs 414:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 1 18 theme HMOs 451:454 arg1 experiments 398:408 combined LC-MS/MS experiments 380:408 combined LC-MS/MS experiments 380:408 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 3 19 theme MS 913:914 arg1 Library 916:922 the NIST 17 Tandem MS Library 894:922 the NIST 17 Tandem MS Library 894:922 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 2 20 theme bootstrap 495:503 arg1 method 521:526 a hybrid search "bootstrap" identification method 478:526 a hybrid search "bootstrap" identification method 478:526 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 6 21 theme human 1302:1306 arg1 milk 1308:1311 human milk 1302:1311 human milk 1302:1311 This new method led to the identification of another 145 oligosaccharides, including an additional 80 HMOs from reanalysis of human milk. 32639750 7 22 theme 219 1414:1416 arg1 oligosaccharides 1423:1438 219 milk oligosaccharides 1414:1438 219 milk oligosaccharides 1414:1438 The newly identified compounds were added to a freely available mass spectral reference database of 219 milk oligosaccharides. 32639750 2 23 from identification 700:713 arg1 milk 749:752 milk 749:752 milk 749:752 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 0 24 theme Bootstrapping 104:116 arg1 Method 118:123 a Hybrid-Search-Based Bootstrapping Method 82:123 a Hybrid-Search-Based Bootstrapping Method 82:123 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 2 25 theme utility 629:635 arg1 use 637:639 utility use 629:639 utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk 629:752 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 2 26 theme rapid 684:688 arg1 identification 700:713 the rapid tentative identification 680:713 the rapid tentative identification of all distinguishable glycans in milk 680:752 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 7 27 theme milk 1418:1421 arg1 oligosaccharides 1423:1438 219 milk oligosaccharides 1414:1438 219 milk oligosaccharides 1414:1438 The newly identified compounds were added to a freely available mass spectral reference database of 219 milk oligosaccharides. 32639750 4 28 theme library 968:974 arg1 construction 976:987 library construction 968:987 library construction of other classes of compounds 968:1017 The general approach appears applicable to library construction of other classes of compounds. 32639750 4 29 theme other 992:996 arg1 classes 998:1004 other classes 992:1004 other classes of compounds 992:1017 The general approach appears applicable to library construction of other classes of compounds. 32639750 2 30 theme search 487:492 arg1 method 521:526 a hybrid search "bootstrap" identification method 478:526 a hybrid search "bootstrap" identification method 478:526 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 3 31 theme Tandem 906:911 arg1 Library 916:922 the NIST 17 Tandem MS Library 894:922 the NIST 17 Tandem MS Library 894:922 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 8 32 theme oligosaccharides 1558:1573 arg1 spectra 1539:1545 spectra 1539:1545 spectra of unknown oligosaccharides 1539:1573 We also provide suggestions to overcome several limitations and pitfalls in the interpretation of spectra of unknown oligosaccharides. 32639750 6 33 theme oligosaccharides 1233:1248 arg1 identification 1203:1216 the identification 1199:1216 the identification of another 145 oligosaccharides, including an additional 80 HMOs from reanalysis of human milk 1199:1311 This new method led to the identification of another 145 oligosaccharides, including an additional 80 HMOs from reanalysis of human milk. 32639750 3 34 from search 857:862 arg1 Library 916:922 the NIST 17 Tandem MS Library 894:922 the NIST 17 Tandem MS Library 894:922 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 3 35 theme previous 793:800 arg1 library 802:808 the previous library 789:808 the previous library 789:808 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 8 36 from pitfalls 1505:1512 arg1 interpretation 1521:1534 the interpretation 1517:1534 the interpretation of spectra of unknown oligosaccharides 1517:1573 We also provide suggestions to overcome several limitations and pitfalls in the interpretation of spectra of unknown oligosaccharides. 32639750 1 37 theme reported 277:284 arg1 library 307:313 a previously reported tandem mass spectral library 264:313 a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 264:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 2 38 theme method 669:674 arg1 use 637:639 utility use 629:639 utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk 629:752 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 7 39 theme spectral 1383:1390 arg1 database 1402:1409 a freely available mass spectral reference database 1359:1409 a freely available mass spectral reference database of 219 milk oligosaccharides 1359:1438 The newly identified compounds were added to a freely available mass spectral reference database of 219 milk oligosaccharides. 32639750 2 40 theme library-based 655:667 arg1 method 669:674 a spectrum library-based method 644:674 a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk 644:752 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 2 41 theme identification 506:519 arg1 method 521:526 a hybrid search "bootstrap" identification method 478:526 a hybrid search "bootstrap" identification method 478:526 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 1 42 theme tandem 286:291 arg1 library 307:313 a previously reported tandem mass spectral library 264:313 a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 264:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 7 43 theme reference 1392:1400 arg1 database 1402:1409 a freely available mass spectral reference database 1359:1409 a freely available mass spectral reference database of 219 milk oligosaccharides 1359:1438 The newly identified compounds were added to a freely available mass spectral reference database of 219 milk oligosaccharides. 32639750 8 44 theme spectra 1539:1545 arg1 interpretation 1521:1534 the interpretation 1517:1534 the interpretation of spectra of unknown oligosaccharides 1517:1573 We also provide suggestions to overcome several limitations and pitfalls in the interpretation of spectra of unknown oligosaccharides. 32639750 0 45 theme Mass 29:32 arg1 Library 43:49 a Mass Spectral Library 27:49 a Mass Spectral Library of Milk Oligosaccharides 27:74 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 1 46 theme mass 293:296 arg1 library 307:313 a previously reported tandem mass spectral library 264:313 a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 264:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 8 47 theme several 1481:1487 arg1 limitations 1489:1499 several limitations 1481:1499 several limitations 1481:1499 We also provide suggestions to overcome several limitations and pitfalls in the interpretation of spectra of unknown oligosaccharides. 32639750 7 48 theme available 1368:1376 arg1 database 1402:1409 a freely available mass spectral reference database 1359:1409 a freely available mass spectral reference database of 219 milk oligosaccharides 1359:1438 The newly identified compounds were added to a freely available mass spectral reference database of 219 milk oligosaccharides. 32639750 2 49 from milk 749:752 arg1 identification 700:713 the rapid tentative identification 680:713 the rapid tentative identification of all distinguishable glycans in milk 680:752 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 2 50 theme present 464:470 arg1 work 472:475 the present work 460:475 the present work 460:475 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 1 51 theme spectral 298:305 arg1 library 307:313 a previously reported tandem mass spectral library 264:313 a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 264:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 4 52 theme general 929:935 arg1 approach 937:944 The general approach 925:944 The general approach 925:944 The general approach appears applicable to library construction of other classes of compounds. 32639750 1 53 theme combined 380:387 arg1 experiments 398:408 combined LC-MS/MS experiments 380:408 combined LC-MS/MS experiments 380:408 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 7 54 theme mass 1378:1381 arg1 database 1402:1409 a freely available mass spectral reference database 1359:1409 a freely available mass spectral reference database of 219 milk oligosaccharides 1359:1438 The newly identified compounds were added to a freely available mass spectral reference database of 219 milk oligosaccharides. 32639750 0 55 theme Library 43:49 arg1 Coverage 15:22 the Coverage 11:22 the Coverage of a Mass Spectral Library of Milk Oligosaccharides 11:74 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 1 56 theme library 307:313 arg1 construction 248:259 construction 248:259 construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 248:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 5 57 from variety 1099:1105 arg1 milks 1086:1090 milks 1086:1090 milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat 1086:1173 The coverage of oligosaccharides was significantly extended using milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat. 32639750 1 58 theme LC-MS/MS 389:396 arg1 experiments 398:408 combined LC-MS/MS experiments 380:408 combined LC-MS/MS experiments 380:408 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 5 59 theme oligosaccharides 1036:1051 arg1 coverage 1024:1031 The coverage 1020:1031 The coverage of oligosaccharides 1020:1051 The coverage of oligosaccharides was significantly extended using milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat. 32639750 3 60 theme hybrid 769:774 arg1 searching 776:784 hybrid searching 769:784 hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library 769:922 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 0 61 theme Spectral 34:41 arg1 Library 43:49 a Mass Spectral Library 27:49 a Mass Spectral Library of Milk Oligosaccharides 27:74 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 0 62 theme Wide 142:145 arg1 Variety 147:153 a Wide Variety 140:153 a Wide Variety of Mammals 140:164 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 0 62 theme Wide 142:145 arg1 Mammals 158:164 Mammals 158:164 Mammals 158:164 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 1 63 theme experiments 398:408 arg1 results 369:375 results 369:375 results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 369:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 5 64 theme African 1152:1158 arg1 lion 1160:1163 African lion 1152:1163 African lion 1152:1163 The coverage of oligosaccharides was significantly extended using milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat. 32639750 6 65 from reanalysis 1288:1297 arg1 HMOs 1278:1281 an additional 80 HMOs 1261:1281 an additional 80 HMOs from reanalysis of human milk 1261:1311 This new method led to the identification of another 145 oligosaccharides, including an additional 80 HMOs from reanalysis of human milk. 32639750 0 66 theme Mammals 158:164 arg1 Variety 147:153 a Wide Variety 140:153 a Wide Variety of Mammals 140:164 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 0 66 theme Mammals 158:164 arg1 Mammals 158:164 Mammals 158:164 Mammals 158:164 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 3 67 dep constructed 828:838 arg1 itself 821:826 itself 821:826 itself 821:826 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 2 68 theme tentative 690:698 arg1 identification 700:713 the rapid tentative identification 680:713 the rapid tentative identification of all distinguishable glycans in milk 680:752 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 3 69 theme oligosaccharide 867:881 arg1 spectra 883:889 oligosaccharide spectra 867:889 oligosaccharide spectra 867:889 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 4 70 theme compounds 1009:1017 arg1 classes 998:1004 other classes 992:1004 other classes of compounds 992:1017 The general approach appears applicable to library construction of other classes of compounds. 32639750 1 71 theme comprehensive 414:426 arg1 analysis 439:446 comprehensive structural analysis 414:446 comprehensive structural analysis of HMOs 414:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 7 72 theme oligosaccharides 1423:1438 arg1 database 1402:1409 a freely available mass spectral reference database 1359:1409 a freely available mass spectral reference database of 219 milk oligosaccharides 1359:1438 The newly identified compounds were added to a freely available mass spectral reference database of 219 milk oligosaccharides. 32639750 3 73 theme hybrid 850:855 arg1 search 857:862 the hybrid search 846:862 the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library 846:922 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 8 74 theme unknown 1550:1556 arg1 oligosaccharides 1558:1573 unknown oligosaccharides 1550:1573 unknown oligosaccharides 1550:1573 We also provide suggestions to overcome several limitations and pitfalls in the interpretation of spectra of unknown oligosaccharides. 32639750 0 75 theme Milk 54:57 arg1 Oligosaccharides 59:74 Milk Oligosaccharides 54:74 Milk Oligosaccharides 54:74 Increasing the Coverage of a Mass Spectral Library of Milk Oligosaccharides Using a Hybrid-Search-Based Bootstrapping Method and Milks from a Wide Variety of Mammals. 32639750 1 76 theme structural 428:437 arg1 analysis 439:446 comprehensive structural analysis 414:446 comprehensive structural analysis of HMOs 414:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 2 77 from glycans 738:744 arg1 milk 749:752 milk 749:752 milk 749:752 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 5 78 theme Asian 1137:1141 arg1 buffalo 1143:1149 Asian buffalo 1137:1149 Asian buffalo 1137:1149 The coverage of oligosaccharides was significantly extended using milks from a variety of mammals, including bovine, Asian buffalo, African lion, and goat. 32639750 7 79 theme identified 1324:1333 arg1 compounds 1335:1343 The newly identified compounds 1314:1343 The newly identified compounds 1314:1343 The newly identified compounds were added to a freely available mass spectral reference database of 219 milk oligosaccharides. 32639750 3 80 theme library 802:808 arg1 searching 776:784 hybrid searching 769:784 hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library 769:922 This involved hybrid searching of the previous library, which was itself constructed using the hybrid search of oligosaccharide spectra in the NIST 17 Tandem MS Library. 32639750 2 81 theme hybrid 480:485 arg1 method 521:526 a hybrid search "bootstrap" identification method 478:526 a hybrid search "bootstrap" identification method 478:526 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 1 82 theme human 321:325 arg1 oligosaccharides 332:347 74 human milk oligosaccharides 318:347 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 318:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 1 82 theme human 321:325 arg1 HMOs 350:353 HMOs 350:353 HMOs 350:353 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 2 83 theme glycans 738:744 arg1 identification 700:713 the rapid tentative identification 680:713 the rapid tentative identification of all distinguishable glycans in milk 680:752 In the present work, a hybrid search "bootstrap" identification method was employed that substantially broadens the coverage of milk oligosaccharides and thereby increases utility use of a spectrum library-based method for the rapid tentative identification of all distinguishable glycans in milk. 32639750 1 84 theme identification 229:242 arg1 method 219:224 method 219:224 method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs 219:454 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 32639750 1 84 theme identification 229:242 arg1 scope 209:213 the scope 205:213 the scope 205:213 This study significantly expands both the scope and method of identification for construction of a previously reported tandem mass spectral library of 74 human milk oligosaccharides (HMOs) derived from results of combined LC-MS/MS experiments and comprehensive structural analysis of HMOs. 6643471 10 0 theme chains 1768:1773 arg1 hCG 1725:1727 normal hCG 1718:1727 normal hCG 1718:1727 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 10 0 theme chains 1768:1773 arg1 sum 1737:1739 the sum total 1733:1745 the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue 1733:1890 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 5 1 theme urinary 717:723 arg1 chains 700:705 the sugar chains 690:705 the sugar chains of normal urinary and placental hCG reported previously 690:761 As compared with the sugar chains of normal urinary and placental hCG reported previously, they include several prominent structural differences. 6643471 8 2 theme alpha-mannosyl 1194:1207 arg1 core 1236:1239 the trimannosyl core 1220:1239 the trimannosyl core 1220:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 8 2 theme alpha-mannosyl 1194:1207 arg1 residue 1209:1215 the same alpha-mannosyl residue 1185:1215 the same alpha-mannosyl residue of the trimannosyl core 1185:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 4 3 theme analysis 663:670 arg1 combination 577:587 the combination 573:587 the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis 573:670 The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. 6643471 5 4 theme placental 729:737 arg1 hCG 739:741 normal urinary and placental hCG 710:741 hCG 739:741 As compared with the sugar chains of normal urinary and placental hCG reported previously, they include several prominent structural differences. 6643471 6 5 theme hCG 872:874 arg1 chains 846:851 the sugar chains 836:851 the sugar chains of choriocarcinoma hCG 836:874 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 2 6 theme asparagine-linked 299:315 arg1 chains 323:328 four asparagine-linked sugar chains 294:328 four asparagine-linked sugar chains 294:328 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 9 7 theme sugar 1434:1438 arg1 chains 1440:1445 the sugar chains 1430:1445 the sugar chains of choriocarcinoma hCG 1430:1468 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 6 8 theme hCG 936:938 arg1 chains 919:924 the sugar chains 909:924 the sugar chains of normal hCG 909:938 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 10 9 theme Gal 1545:1547 arg1 beta 1549:1552 Gal beta 1 1545:1554 Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3 1545:1611 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 5 10 theme sugar 694:698 arg1 chains 700:705 the sugar chains 690:705 the sugar chains of normal urinary and placental hCG reported previously 690:761 As compared with the sugar chains of normal urinary and placental hCG reported previously, they include several prominent structural differences. 6643471 10 11 gly fucosylated 1750:1760 arg1 chains 1768:1773 fucosylated sugar chains 1750:1773 fucosylated sugar chains 1750:1773 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 8 12 theme trimannosyl 1224:1234 arg1 core 1236:1239 the trimannosyl core 1220:1239 the trimannosyl core 1220:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 6 13 theme sugar 840:844 arg1 chains 846:851 the sugar chains 836:851 the sugar chains of choriocarcinoma hCG 836:874 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 9 14 theme hCG 1466:1468 arg1 chains 1440:1445 the sugar chains 1430:1445 the sugar chains of choriocarcinoma hCG 1430:1468 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 10 15 dep Asn 1698:1700 arg1 found 1709:1713 found 1709:1713 is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue 1702:1890 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 10 16 theme 2Man 1589:1592 arg1 alpha 1594:1598 2Man alpha 1 1589:1600 2Man alpha 1 1589:1600 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 5 17 theme prominent 785:793 arg1 differences 806:816 several prominent structural differences 777:816 several prominent structural differences 777:816 As compared with the sugar chains of normal urinary and placental hCG reported previously, they include several prominent structural differences. 6643471 6 18 from acid 897:900 arg1 free 880:883 free 880:883 free 880:883 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 9 19 theme sugar 1293:1297 arg1 chains 1299:1304 any triantennary sugar chains 1276:1304 any triantennary sugar chains 1276:1304 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 1 20 theme sugar 137:141 arg1 chains 143:148 triantennary sugar chains 124:148 triantennary sugar chains 124:148 Appearance of triantennary sugar chains and unique biantennary sugar chains. 6643471 7 21 theme sugar 1091:1095 arg1 chains 1097:1102 regular tri-, bi-, and monoantennary sugar chains 1054:1102 regular tri-, bi-, and monoantennary sugar chains 1054:1102 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 7 22 theme regular 1054:1060 arg1 chains 1097:1102 regular tri-, bi-, and monoantennary sugar chains 1054:1102 regular tri-, bi-, and monoantennary sugar chains 1054:1102 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 3 23 theme sugar 351:355 arg1 chains 357:362 The sugar chains 347:362 The sugar chains 347:362 The sugar chains were quantitatively liberated as radioactive oligosaccharides from polypeptide portion by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. 6643471 0 24 theme chorionic 58:66 arg1 gonadotropin 68:79 human chorionic gonadotropin 52:79 human chorionic gonadotropin 52:79 Structures of the asparagine-linked sugar chains of human chorionic gonadotropin produced in choriocarcinoma. 6643471 3 25 from portion 443:449 arg1 oligosaccharides 409:424 radioactive oligosaccharides 397:424 radioactive oligosaccharides from polypeptide portion 397:449 The sugar chains were quantitatively liberated as radioactive oligosaccharides from polypeptide portion by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. 6643471 1 26 theme biantennary 161:171 arg1 chains 179:184 unique biantennary sugar chains 154:184 unique biantennary sugar chains 154:184 Appearance of triantennary sugar chains and unique biantennary sugar chains. 6643471 9 27 theme beta 1325:1328 arg1 occurrence 1307:1316 occurrence 1307:1316 occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 1307:1376 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 1 28 theme chains 179:184 arg1 Appearance 110:119 Appearance 110:119 Appearance of triantennary sugar chains and unique biantennary sugar chains. 110:185 Appearance of triantennary sugar chains and unique biantennary sugar chains. 6643471 10 29 dep leads 1648:1652 arg1 leads 1689:1693 leads 1689:1693 leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue 1689:1890 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 6 30 gly sialylated 952:961 arg1 chains 919:924 the sugar chains 909:924 the sugar chains of normal hCG 909:938 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 7 31 theme complex-type 1013:1024 arg1 chains 1032:1037 unusual biantennary complex-type sugar chains 993:1037 unusual biantennary complex-type sugar chains 993:1037 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 9 32 theme 4GlcNAc 1341:1347 arg1 beta 1349:1352 4GlcNAc beta 1 1341:1354 4GlcNAc beta 1 leads to 4Man alpha 1 1341:1376 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 7 33 theme unusual 993:999 arg1 chains 1032:1037 unusual biantennary complex-type sugar chains 993:1037 unusual biantennary complex-type sugar chains 993:1037 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 4 34 theme sugar 541:545 arg1 chains 547:552 these sugar chains 535:552 these sugar chains 535:552 The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. 6643471 2 35 contain contains 285:292 arg1 gonadotropin 203:214 Human chorionic gonadotropin 187:214 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma 187:283 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 2 35 contain contains 285:292 arg1 molecule 337:344 one molecule 333:344 one molecule 333:344 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 2 35 contain contains 285:292 arg2 chains 323:328 four asparagine-linked sugar chains 294:328 four asparagine-linked sugar chains 294:328 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 2 35 contain contains 285:292 arg1 hCG 217:219 hCG 217:219 hCG 217:219 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 2 35 contain contains 285:292 arg2 gonadotropin 203:214 Human chorionic gonadotropin 187:214 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma 187:283 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 2 35 contain contains 285:292 arg2 hCG 217:219 hCG 217:219 hCG 217:219 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 3 36 theme radioactive 397:407 arg1 oligosaccharides 409:424 radioactive oligosaccharides 397:424 radioactive oligosaccharides from polypeptide portion 397:449 The sugar chains were quantitatively liberated as radioactive oligosaccharides from polypeptide portion by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. 6643471 4 37 theme digestion 615:623 arg1 combination 577:587 the combination 573:587 the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis 573:670 The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. 6643471 4 38 theme periodate 626:634 arg1 oxidation 636:644 periodate oxidation 626:644 periodate oxidation 626:644 The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. 6643471 10 39 theme monoantennary 1493:1505 arg1 chain 1513:1517 the monoantennary sugar chain 1489:1517 the monoantennary sugar chain of Man alpha 1 1489:1532 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 2 40 theme chorionic 193:201 arg1 hCG 217:219 hCG 217:219 hCG 217:219 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 2 40 theme chorionic 193:201 arg1 gonadotropin 203:214 Human chorionic gonadotropin 187:214 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma 187:283 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 10 41 theme Man 1613:1615 arg1 beta 1617:1620 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 1543:1622 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 1543:1622 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 0 42 theme sugar 36:40 arg1 chains 42:47 the asparagine-linked sugar chains 14:47 the asparagine-linked sugar chains of human chorionic gonadotropin 14:79 Structures of the asparagine-linked sugar chains of human chorionic gonadotropin produced in choriocarcinoma. 6643471 3 43 dep N-acetylation 481:493 arg1 reduction 506:514 reduction 506:514 reduction 506:514 The sugar chains were quantitatively liberated as radioactive oligosaccharides from polypeptide portion by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. 6643471 9 44 dep beta 1349:1352 arg1 leads 1356:1360 leads 1356:1360 leads to 4Man alpha 1 1356:1376 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 10 45 theme normal 1718:1723 arg1 hCG 1725:1727 normal hCG 1718:1727 normal hCG 1718:1727 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 10 46 theme sugar 1762:1766 arg1 chains 1768:1773 fucosylated sugar chains 1750:1773 fucosylated sugar chains 1750:1773 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 4 47 theme sequential 592:601 arg1 digestion 615:623 sequential glycosidase digestion 592:623 sequential glycosidase digestion 592:623 The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. 6643471 10 48 theme Man 1522:1524 arg1 alpha 1526:1530 Man alpha 1 1522:1532 Man alpha 1 1522:1532 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 7 49 theme Choriocarcinoma 964:978 arg1 hCG 980:982 Choriocarcinoma hCG 964:982 Choriocarcinoma hCG 964:982 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 8 50 theme C-2 1160:1162 arg1 positions 1172:1180 the C-2 and C-4 positions 1156:1180 the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core 1156:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 6 51 theme sialic 890:895 arg1 acid 897:900 sialic acid 890:900 sialic acid 890:900 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 8 52 attach linked 1146:1151 arg3 positions 1172:1180 the C-2 and C-4 positions 1156:1180 the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core 1156:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 8 52 attach linked 1146:1151 arg2 chains 1139:1144 two outer chains 1129:1144 two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core 1129:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 10 53 dep sum 1737:1739 arg1 % 1780:1780 50% 1778:1780 50% 1778:1780 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 8 54 theme C-4 1168:1170 arg1 positions 1172:1180 the C-2 and C-4 positions 1156:1180 the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core 1156:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 10 55 gly fucosylation 1836:1847 arg1 tissue 1885:1890 choriocarcinoma tissue 1869:1890 choriocarcinoma tissue 1869:1890 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 0 56 link asparagine-linked 18:34 arg1 chains 42:47 the asparagine-linked sugar chains 14:47 the asparagine-linked sugar chains of human chorionic gonadotropin 14:79 Structures of the asparagine-linked sugar chains of human chorionic gonadotropin produced in choriocarcinoma. 6643471 9 57 dep occurrence 1307:1316 arg1 leads 1332:1336 leads 1332:1336 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 1332:1376 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 9 58 theme normal 1248:1253 arg1 hCG 1255:1257 normal hCG 1248:1257 normal hCG 1248:1257 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 2 59 theme sugar 317:321 arg1 chains 323:328 four asparagine-linked sugar chains 294:328 four asparagine-linked sugar chains 294:328 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 8 60 theme same 1189:1192 arg1 core 1236:1239 the trimannosyl core 1220:1239 the trimannosyl core 1220:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 8 60 theme same 1189:1192 arg1 residue 1209:1215 the same alpha-mannosyl residue 1185:1215 the same alpha-mannosyl residue of the trimannosyl core 1185:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 4 61 theme methylation 651:661 arg1 analysis 663:670 methylation analysis 651:670 methylation analysis 651:670 The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. 6643471 6 62 theme choriocarcinoma 856:870 arg1 hCG 872:874 choriocarcinoma hCG 856:874 choriocarcinoma hCG 856:874 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 10 63 theme Fuc 1659:1661 arg1 alpha 1663:1667 Fuc alpha 1 1659:1669 Fuc alpha 1 1659:1669 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 9 64 theme chains 1440:1445 arg1 feature 1419:1425 another characteristic feature 1396:1425 another characteristic feature of the sugar chains of choriocarcinoma hCG 1396:1468 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 8 65 theme residue 1209:1215 arg1 positions 1172:1180 the C-2 and C-4 positions 1156:1180 the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core 1156:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 6 66 theme normal 929:934 arg1 hCG 936:938 normal hCG 929:938 normal hCG 929:938 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 7 67 contain contains 984:991 arg1 hCG 980:982 Choriocarcinoma hCG 964:982 Choriocarcinoma hCG 964:982 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 7 67 contain contains 984:991 arg2 chains 1032:1037 unusual biantennary complex-type sugar chains 993:1037 unusual biantennary complex-type sugar chains 993:1037 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 6 68 theme chains 846:851 arg1 chains 846:851 the sugar chains 836:851 the sugar chains of choriocarcinoma hCG 836:874 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 6 68 theme chains 846:851 arg1 % 831:831 More than 97% 819:831 More than 97% of the sugar chains of choriocarcinoma hCG 819:874 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 9 69 theme choriocarcinoma 1450:1464 arg1 hCG 1466:1468 choriocarcinoma hCG 1450:1468 choriocarcinoma hCG 1450:1468 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 10 70 theme 4GlcNAc 1565:1571 arg1 beta 1573:1576 4GlcNAc beta 1 1565:1578 4GlcNAc beta 1 1565:1578 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 10 71 dep beta 1549:1552 arg1 leads 1602:1606 leads 1602:1606 leads to 3 1602:1611 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 10 71 dep beta 1549:1552 arg1 leads 1580:1584 leads 1580:1584 leads to 2Man alpha 1 1580:1600 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 10 71 dep beta 1549:1552 arg1 leads 1556:1560 leads 1556:1560 leads to 4GlcNAc beta 1 1556:1578 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 8 72 theme core 1236:1239 arg1 core 1236:1239 the trimannosyl core 1220:1239 the trimannosyl core 1220:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 8 72 theme core 1236:1239 arg1 residue 1209:1215 the same alpha-mannosyl residue 1185:1215 the same alpha-mannosyl residue of the trimannosyl core 1185:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 10 73 dep GlcNAc 1682:1687 arg1 leads 1671:1675 leads 1671:1675 leads to 6 1671:1680 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 2 74 link asparagine-linked 299:315 arg1 chains 323:328 four asparagine-linked sugar chains 294:328 four asparagine-linked sugar chains 294:328 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 5 75 theme several 777:783 arg1 differences 806:816 several prominent structural differences 777:816 several prominent structural differences 777:816 As compared with the sugar chains of normal urinary and placental hCG reported previously, they include several prominent structural differences. 6643471 2 76 with patient 256:262 arg1 choriocarcinoma 269:283 choriocarcinoma 269:283 choriocarcinoma 269:283 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 5 77 theme hCG 739:741 arg1 chains 700:705 the sugar chains 690:705 the sugar chains of normal urinary and placental hCG reported previously 690:761 As compared with the sugar chains of normal urinary and placental hCG reported previously, they include several prominent structural differences. 6643471 9 78 theme triantennary 1280:1291 arg1 chains 1299:1304 any triantennary sugar chains 1276:1304 any triantennary sugar chains 1276:1304 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 1 79 theme triantennary 124:135 arg1 chains 143:148 triantennary sugar chains 124:148 triantennary sugar chains 124:148 Appearance of triantennary sugar chains and unique biantennary sugar chains. 6643471 10 80 theme normal 1809:1814 arg1 hCG 1816:1818 normal hCG 1809:1818 normal hCG 1809:1818 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 7 81 theme monoantennary 1077:1089 arg1 chains 1097:1102 regular tri-, bi-, and monoantennary sugar chains 1054:1102 regular tri-, bi-, and monoantennary sugar chains 1054:1102 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 7 82 theme bi- 1068:1070 arg1 chains 1097:1102 regular tri-, bi-, and monoantennary sugar chains 1054:1102 regular tri-, bi-, and monoantennary sugar chains 1054:1102 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 1 83 theme chains 143:148 arg1 Appearance 110:119 Appearance 110:119 Appearance of triantennary sugar chains and unique biantennary sugar chains. 110:185 Appearance of triantennary sugar chains and unique biantennary sugar chains. 6643471 9 84 contain contain 1268:1274 arg2 chains 1299:1304 any triantennary sugar chains 1276:1304 any triantennary sugar chains 1276:1304 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 9 84 contain contain 1268:1274 arg1 hCG 1255:1257 normal hCG 1248:1257 normal hCG 1248:1257 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 0 85 theme gonadotropin 68:79 arg1 chains 42:47 the asparagine-linked sugar chains 14:47 the asparagine-linked sugar chains of human chorionic gonadotropin 14:79 Structures of the asparagine-linked sugar chains of human chorionic gonadotropin produced in choriocarcinoma. 6643471 2 86 theme patient 256:262 arg1 urine 243:247 urine 243:247 urine of the patient with choriocarcinoma 243:283 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 7 87 theme tri- 1062:1065 arg1 chains 1097:1102 regular tri-, bi-, and monoantennary sugar chains 1054:1102 regular tri-, bi-, and monoantennary sugar chains 1054:1102 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 1 88 theme unique 154:159 arg1 chains 179:184 unique biantennary sugar chains 154:184 unique biantennary sugar chains 154:184 Appearance of triantennary sugar chains and unique biantennary sugar chains. 6643471 9 89 theme Gal 1321:1323 arg1 beta 1325:1328 Gal beta 1 1321:1330 Gal beta 1 1321:1330 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 1 90 theme sugar 173:177 arg1 chains 179:184 unique biantennary sugar chains 154:184 unique biantennary sugar chains 154:184 Appearance of triantennary sugar chains and unique biantennary sugar chains. 6643471 10 91 theme choriocarcinoma 1869:1883 arg1 tissue 1885:1890 choriocarcinoma tissue 1869:1890 choriocarcinoma tissue 1869:1890 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 5 92 theme structural 795:804 arg1 differences 806:816 several prominent structural differences 777:816 several prominent structural differences 777:816 As compared with the sugar chains of normal urinary and placental hCG reported previously, they include several prominent structural differences. 6643471 9 93 dep leads 1378:1382 arg1 feature 1419:1425 another characteristic feature 1396:1425 another characteristic feature of the sugar chains of choriocarcinoma hCG 1396:1468 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 8 94 theme sugar 1111:1115 arg1 chains 1117:1122 These sugar chains 1105:1122 These sugar chains 1105:1122 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 7 95 theme sugar 1026:1030 arg1 chains 1032:1037 unusual biantennary complex-type sugar chains 993:1037 unusual biantennary complex-type sugar chains 993:1037 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 4 96 theme chains 547:552 arg1 structures 521:530 The structures 517:530 The structures of these sugar chains 517:552 The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. 6643471 8 97 contain have 1124:1127 arg1 chains 1117:1122 These sugar chains 1105:1122 These sugar chains 1105:1122 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 8 97 contain have 1124:1127 arg2 chains 1139:1144 two outer chains 1129:1144 two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core 1129:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 7 98 theme biantennary 1001:1011 arg1 chains 1032:1037 unusual biantennary complex-type sugar chains 993:1037 unusual biantennary complex-type sugar chains 993:1037 Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. 6643471 3 99 theme polypeptide 431:441 arg1 portion 443:449 polypeptide portion 431:449 polypeptide portion 431:449 The sugar chains were quantitatively liberated as radioactive oligosaccharides from polypeptide portion by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. 6643471 0 100 theme asparagine-linked 18:34 arg1 chains 42:47 the asparagine-linked sugar chains 14:47 the asparagine-linked sugar chains of human chorionic gonadotropin 14:79 Structures of the asparagine-linked sugar chains of human chorionic gonadotropin produced in choriocarcinoma. 6643471 8 101 theme outer 1133:1137 arg1 chains 1139:1144 two outer chains 1129:1144 two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core 1129:1239 These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. 6643471 4 102 theme oxidation 636:644 arg1 combination 577:587 the combination 573:587 the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis 573:670 The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. 6643471 10 103 theme sugar 1507:1511 arg1 chain 1513:1517 the monoantennary sugar chain 1489:1517 the monoantennary sugar chain of Man alpha 1 1489:1532 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 0 104 theme chains 42:47 arg1 Structures 0:9 Structures 0:9 Structures of the asparagine-linked sugar chains of human chorionic gonadotropin 0:79 Structures of the asparagine-linked sugar chains of human chorionic gonadotropin produced in choriocarcinoma. 6643471 9 105 theme 4Man 1365:1368 arg1 alpha 1370:1374 4Man alpha 1 1365:1376 4Man alpha 1 1365:1376 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 6643471 6 106 theme sugar 913:917 arg1 chains 919:924 the sugar chains 909:924 the sugar chains of normal hCG 909:938 More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. 6643471 2 107 theme Human 187:191 arg1 hCG 217:219 hCG 217:219 hCG 217:219 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 2 107 theme Human 187:191 arg1 gonadotropin 203:214 Human chorionic gonadotropin 187:214 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma 187:283 Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. 6643471 0 108 theme human 52:56 arg1 gonadotropin 68:79 human chorionic gonadotropin 52:79 human chorionic gonadotropin 52:79 Structures of the asparagine-linked sugar chains of human chorionic gonadotropin produced in choriocarcinoma. 6643471 4 109 theme glycosidase 603:613 arg1 digestion 615:623 sequential glycosidase digestion 592:623 sequential glycosidase digestion 592:623 The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. 6643471 10 110 theme alpha 1526:1530 arg1 chain 1513:1517 the monoantennary sugar chain 1489:1517 the monoantennary sugar chain of Man alpha 1 1489:1532 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 10 111 theme fucosylated 1750:1760 arg1 chains 1768:1773 fucosylated sugar chains 1750:1773 fucosylated sugar chains 1750:1773 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 10 112 dep beta 1617:1620 arg1 beta 1549:1552 Gal beta 1 1545:1554 Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3 1545:1611 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 10 113 theme 4GlcNAc 1633:1639 arg1 beta 1641:1644 4GlcNAc beta 1 1633:1646 4GlcNAc beta 1 1633:1646 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 10 114 theme total 1741:1745 arg1 sum 1737:1739 the sum total 1733:1745 the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue 1733:1890 The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue. 6643471 9 115 theme characteristic 1404:1417 arg1 feature 1419:1425 another characteristic feature 1396:1425 another characteristic feature of the sugar chains of choriocarcinoma hCG 1396:1468 Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. 25685702 4 0 theme false 461:465 arg1 FDR 483:485 FDR 483:485 FDR 483:485 Statistically significant false discovery rate (FDR)-adjusted p-values were observed for 18 glycans, eight that differed significantly between NAG and GC, three that distinguished NAG from DU, and eight that differed between DU and GC. 25685702 4 0 theme false 461:465 arg1 rate 477:480 Statistically significant false discovery rate 435:480 Statistically significant false discovery rate (FDR) 435:486 Statistically significant false discovery rate (FDR)-adjusted p-values were observed for 18 glycans, eight that differed significantly between NAG and GC, three that distinguished NAG from DU, and eight that differed between DU and GC. 25685702 1 1 from stage 138:142 arg1 detection 96:104 detection 96:104 detection of gastric cancer at an earlier stage 96:142 Biomarkers may facilitate detection of gastric cancer at an earlier stage and reduce mortality. 25685702 1 2 theme cancer 117:122 arg1 detection 96:104 detection 96:104 detection of gastric cancer at an earlier stage 96:142 Biomarkers may facilitate detection of gastric cancer at an earlier stage and reduce mortality. 25685702 4 3 theme significant 449:459 arg1 FDR 483:485 FDR 483:485 FDR 483:485 Statistically significant false discovery rate (FDR)-adjusted p-values were observed for 18 glycans, eight that differed significantly between NAG and GC, three that distinguished NAG from DU, and eight that differed between DU and GC. 25685702 4 3 theme significant 449:459 arg1 rate 477:480 Statistically significant false discovery rate 435:480 Statistically significant false discovery rate (FDR) 435:486 Statistically significant false discovery rate (FDR)-adjusted p-values were observed for 18 glycans, eight that differed significantly between NAG and GC, three that distinguished NAG from DU, and eight that differed between DU and GC. 25685702 0 4 theme Serum 4:8 arg1 Signature 41:49 The Serum Immunoglobulin G Glycosylation Signature 0:49 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 0:68 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 25685702 2 5 theme gastric 341:347 arg1 cancer 349:354 gastric cancer 341:354 gastric cancer (GC) 341:359 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 5 theme gastric 341:347 arg1 GC 357:358 GC 357:358 GC 357:358 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 0 6 theme G 25:25 arg1 Signature 41:49 The Serum Immunoglobulin G Glycosylation Signature 0:49 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 0:68 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 25685702 2 7 theme non-atrophic 287:298 arg1 NAG 311:313 NAG 311:313 NAG 311:313 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 7 theme non-atrophic 287:298 arg1 gastritis 300:308 non-atrophic gastritis 287:308 non-atrophic gastritis (NAG) 287:314 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 3 8 theme nano-LC-TOF 404:414 arg1 spectrometry 421:432 nano-LC-TOF mass spectrometry 404:432 nano-LC-TOF mass spectrometry 404:432 Serum IgG was released and analyzed using nano-LC-TOF mass spectrometry. 25685702 0 9 theme Immunoglobulin 10:23 arg1 Signature 41:49 The Serum Immunoglobulin G Glycosylation Signature 0:49 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 0:68 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 25685702 1 10 theme gastric 109:115 arg1 cancer 117:122 gastric cancer 109:122 gastric cancer 109:122 Biomarkers may facilitate detection of gastric cancer at an earlier stage and reduce mortality. 25685702 3 11 theme mass 416:419 arg1 spectrometry 421:432 nano-LC-TOF mass spectrometry 404:432 nano-LC-TOF mass spectrometry 404:432 Serum IgG was released and analyzed using nano-LC-TOF mass spectrometry. 25685702 2 12 theme serum 226:230 arg1 G 247:247 serum immunoglobulin G 226:247 serum immunoglobulin G (IgG) 226:253 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 12 theme serum 226:230 arg1 IgG 250:252 IgG 250:252 IgG 250:252 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 0 13 theme Glycosylation 27:39 arg1 Signature 41:49 The Serum Immunoglobulin G Glycosylation Signature 0:49 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 0:68 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 25685702 3 14 theme Serum 362:366 arg1 IgG 368:370 Serum IgG 362:370 Serum IgG 362:370 Serum IgG was released and analyzed using nano-LC-TOF mass spectrometry. 25685702 0 15 theme Gastric 54:60 arg1 Cancer 62:67 Gastric Cancer 54:67 Gastric Cancer 54:67 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 25685702 5 16 theme glycosylation 679:691 arg1 signature 693:701 The IgG glycosylation signature 671:701 The IgG glycosylation signature 671:701 The IgG glycosylation signature may be useful as a predictive marker for gastric cancer. 25685702 5 16 theme glycosylation 679:691 arg1 useful 710:715 useful 710:715 useful 710:715 The IgG glycosylation signature may be useful as a predictive marker for gastric cancer. 25685702 2 17 theme duodenal 317:324 arg1 DU 333:334 DU 333:334 DU 333:334 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 17 theme duodenal 317:324 arg1 ulcer 326:330 duodenal ulcer 317:330 duodenal ulcer (DU) 317:335 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 18 theme glycosylation 201:213 arg1 profile 215:221 the glycosylation profile 197:221 the glycosylation profile of serum immunoglobulin G (IgG) 197:253 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 19 gly glycosylation 201:213 arg1 G 247:247 serum immunoglobulin G 226:247 serum immunoglobulin G (IgG) 226:253 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 19 gly glycosylation 201:213 arg1 IgG 250:252 IgG 250:252 IgG 250:252 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 5 20 theme gastric 744:750 arg1 cancer 752:757 gastric cancer 744:757 gastric cancer 744:757 The IgG glycosylation signature may be useful as a predictive marker for gastric cancer. 25685702 1 21 theme earlier 130:136 arg1 stage 138:142 an earlier stage 127:142 an earlier stage 127:142 Biomarkers may facilitate detection of gastric cancer at an earlier stage and reduce mortality. 25685702 5 22 theme IgG 675:677 arg1 signature 693:701 The IgG glycosylation signature 671:701 The IgG glycosylation signature 671:701 The IgG glycosylation signature may be useful as a predictive marker for gastric cancer. 25685702 5 22 theme IgG 675:677 arg1 useful 710:715 useful 710:715 useful 710:715 The IgG glycosylation signature may be useful as a predictive marker for gastric cancer. 25685702 2 23 theme G 247:247 arg1 profile 215:221 the glycosylation profile 197:221 the glycosylation profile of serum immunoglobulin G (IgG) 197:253 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 24 with patients 273:280 arg1 cancer 349:354 gastric cancer 341:354 gastric cancer (GC) 341:359 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 24 with patients 273:280 arg1 gastritis 300:308 non-atrophic gastritis 287:308 non-atrophic gastritis (NAG) 287:314 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 24 with patients 273:280 arg1 ulcer 326:330 duodenal ulcer 317:330 duodenal ulcer (DU) 317:335 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 24 with patients 273:280 arg1 DU 333:334 DU 333:334 DU 333:334 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 24 with patients 273:280 arg1 GC 357:358 GC 357:358 GC 357:358 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 24 with patients 273:280 arg1 NAG 311:313 NAG 311:313 NAG 311:313 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 0 25 theme Cancer 62:67 arg1 Signature 41:49 The Serum Immunoglobulin G Glycosylation Signature 0:49 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 0:68 The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer. 25685702 4 26 theme discovery 467:475 arg1 FDR 483:485 FDR 483:485 FDR 483:485 Statistically significant false discovery rate (FDR)-adjusted p-values were observed for 18 glycans, eight that differed significantly between NAG and GC, three that distinguished NAG from DU, and eight that differed between DU and GC. 25685702 4 26 theme discovery 467:475 arg1 rate 477:480 Statistically significant false discovery rate 435:480 Statistically significant false discovery rate (FDR) 435:486 Statistically significant false discovery rate (FDR)-adjusted p-values were observed for 18 glycans, eight that differed significantly between NAG and GC, three that distinguished NAG from DU, and eight that differed between DU and GC. 25685702 2 27 theme immunoglobulin 232:245 arg1 G 247:247 serum immunoglobulin G 226:247 serum immunoglobulin G (IgG) 226:253 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 2 27 theme immunoglobulin 232:245 arg1 IgG 250:252 IgG 250:252 IgG 250:252 Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). 25685702 5 28 theme predictive 722:731 arg1 marker 733:738 a predictive marker 720:738 a predictive marker for gastric cancer 720:757 The IgG glycosylation signature may be useful as a predictive marker for gastric cancer. 34725484 0 0 theme serum 109:113 arg1 analysis 128:135 serum glycopeptide analysis 109:135 serum glycopeptide analysis 109:135 Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis. 34725484 4 1 theme mass 581:584 arg1 datasets 620:627 The same mass spectrometrybased glycoproteomics datasets 572:627 The same mass spectrometrybased glycoproteomics datasets from human serum 572:644 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 7 2 theme future 1324:1329 arg1 developments 1340:1351 future software developments 1324:1351 future software developments 1324:1351 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 1 3 theme research 197:204 arg1 Glycoproteomics 138:152 Glycoproteomics 138:152 Glycoproteomics 138:152 Glycoproteomics is a powerful yet analytically challenging research tool. 34725484 1 3 theme research 197:204 arg1 tool 206:209 a powerful yet analytically challenging research tool 157:209 a powerful yet analytically challenging research tool 157:209 Glycoproteomics is a powerful yet analytically challenging research tool. 34725484 7 4 from decision-making 1376:1390 arg1 glycoproteomics 1395:1409 glycoproteomics 1395:1409 glycoproteomics 1395:1409 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 4 5 theme relative 684:691 arg1 performance 698:708 the relative team performance 680:708 the relative team performance for N- and O-glycopeptide data analysis 680:749 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 3 6 theme HUPO 386:389 arg1 Initiative 413:422 the HUPO Human Glycoproteomics Initiative 382:422 the HUPO Human Glycoproteomics Initiative 382:422 Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. 34725484 6 7 theme high-accuracy 1074:1086 arg1 solutions 1112:1120 improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions 1044:1120 improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions 1044:1120 Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. 34725484 7 8 theme software 1331:1338 arg1 developments 1340:1351 future software developments 1324:1351 future software developments 1324:1351 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 6 9 theme performance-associated 972:993 arg1 parameters 1002:1011 key performance-associated search parameters 968:1011 key performance-associated search parameters 968:1011 Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. 34725484 5 10 theme several 852:858 arg1 strategies 905:914 several high-performance glycoproteomics informatics strategies 852:914 several high-performance glycoproteomics informatics strategies 852:914 Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. 34725484 4 11 theme glycoproteomics 604:618 arg1 datasets 620:627 The same mass spectrometrybased glycoproteomics datasets 572:627 The same mass spectrometrybased glycoproteomics datasets from human serum 572:644 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 7 12 theme diverse 1149:1155 arg1 packages 1166:1173 diverse software packages 1149:1173 diverse software packages for comprehensive glycopeptide data analysis 1149:1218 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 6 13 theme key 968:970 arg1 parameters 1002:1011 key performance-associated search parameters 968:1011 key performance-associated search parameters 968:1011 Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. 34725484 0 14 theme glycopeptide 115:126 arg1 analysis 128:135 serum glycopeptide analysis 109:135 serum glycopeptide analysis 109:135 Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis. 34725484 4 15 theme data 737:740 arg1 analysis 742:749 O-glycopeptide data analysis 722:749 O-glycopeptide data analysis 722:749 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 6 16 theme Deep 933:936 arg1 analysis 938:945 Deep analysis 933:945 Deep analysis of the data 933:957 Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. 34725484 4 17 theme team 693:696 arg1 performance 698:708 the relative team performance 680:708 the relative team performance for N- and O-glycopeptide data analysis 680:749 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 5 18 theme glycoproteomics 877:891 arg1 strategies 905:914 several high-performance glycoproteomics informatics strategies 852:914 several high-performance glycoproteomics informatics strategies 852:914 Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. 34725484 4 19 gly O-glycopeptide 722:735 arg2 O-glycopeptide 722:735 O-glycopeptide data analysis 722:749 O-glycopeptide data analysis 722:749 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 2 20 theme relative 325:332 arg1 performance 334:344 their relative performance 319:344 their relative performance 319:344 Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. 34725484 4 21 theme performance 797:807 arg1 tests 809:813 orthogonal performance tests 786:813 orthogonal performance tests 786:813 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 5 22 theme informatics 893:903 arg1 strategies 905:914 several high-performance glycoproteomics informatics strategies 852:914 several high-performance glycoproteomics informatics strategies 852:914 Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. 34725484 4 23 theme same 576:579 arg1 datasets 620:627 The same mass spectrometrybased glycoproteomics datasets 572:627 The same mass spectrometrybased glycoproteomics datasets from human serum 572:644 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 0 24 gly glycopeptide 115:126 arg2 glycopeptide 115:126 serum glycopeptide analysis 109:135 serum glycopeptide analysis 109:135 Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis. 34725484 7 25 theme several 1237:1243 arg1 strategies 1269:1278 several high-performance search strategies 1237:1278 several high-performance search strategies 1237:1278 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 3 26 theme glycoproteomics 487:501 arg1 software 503:510 glycoproteomics software 487:510 glycoproteomics software 487:510 Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. 34725484 0 27 theme Community 0:8 arg1 evaluation 10:19 Community evaluation 0:19 Community evaluation of glycoproteomics informatics solutions 0:60 Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis. 34725484 7 28 theme informatics 1364:1374 arg1 decision-making 1376:1390 informatics decision-making 1364:1390 informatics decision-making in glycoproteomics 1364:1409 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 7 29 theme key 1294:1296 arg1 variables 1298:1306 key variables 1294:1306 key variables that will guide future software developments and assist informatics decision-making in glycoproteomics 1294:1409 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 3 30 theme software 503:510 arg1 users 478:482 users 478:482 users 478:482 Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. 34725484 3 30 theme software 503:510 arg1 developers 463:472 developers 463:472 developers 463:472 Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. 34725484 0 31 theme glycoproteomics 24:38 arg1 solutions 52:60 glycoproteomics informatics solutions 24:60 glycoproteomics informatics solutions 24:60 Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis. 34725484 6 32 theme data 954:957 arg1 analysis 938:945 Deep analysis 933:945 Deep analysis of the data 933:957 Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. 34725484 3 33 gly glycopeptide 549:560 arg2 glycopeptide 549:560 system-wide glycopeptide analysis 537:569 system-wide glycopeptide analysis 537:569 Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. 34725484 3 34 theme system-wide 537:547 arg1 analysis 562:569 system-wide glycopeptide analysis 537:569 system-wide glycopeptide analysis 537:569 Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. 34725484 6 35 theme improved 1044:1051 arg1 solutions 1112:1120 improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions 1044:1120 improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions 1044:1120 Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. 34725484 3 36 theme glycopeptide 549:560 arg1 analysis 562:569 system-wide glycopeptide analysis 537:569 system-wide glycopeptide analysis 537:569 Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. 34725484 0 37 theme solutions 52:60 arg1 evaluation 10:19 Community evaluation 0:19 Community evaluation of glycoproteomics informatics solutions 0:60 Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis. 34725484 7 38 theme high-performance 1245:1260 arg1 strategies 1269:1278 several high-performance search strategies 1237:1278 several high-performance search strategies 1237:1278 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 2 39 theme spectra 292:298 arg1 interpretation 241:254 the interpretation 237:254 the interpretation of complex glycopeptide tandem mass spectra 237:298 Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. 34725484 4 40 theme orthogonal 786:795 arg1 tests 809:813 orthogonal performance tests 786:813 orthogonal performance tests 786:813 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 0 41 theme informatics 40:50 arg1 solutions 52:60 glycoproteomics informatics solutions 24:60 glycoproteomics informatics solutions 24:60 Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis. 34725484 4 42 theme human 634:638 arg1 serum 640:644 human serum 634:644 human serum 634:644 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 4 43 from serum 640:644 arg1 datasets 620:627 The same mass spectrometrybased glycoproteomics datasets 572:627 The same mass spectrometrybased glycoproteomics datasets from human serum 572:644 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 2 44 theme Software 212:219 arg1 packages 221:228 Software packages 212:228 Software packages aiding the interpretation of complex glycopeptide tandem mass spectra 212:298 Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. 34725484 2 45 theme mass 287:290 arg1 spectra 292:298 complex glycopeptide tandem mass spectra 259:298 complex glycopeptide tandem mass spectra 259:298 Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. 34725484 7 46 gly glycopeptide 1193:1204 arg2 glycopeptide 1193:1204 comprehensive glycopeptide data analysis 1179:1218 comprehensive glycopeptide data analysis 1179:1218 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 0 47 theme high-performance 70:85 arg1 strategies 94:103 high-performance search strategies 70:103 high-performance search strategies for serum glycopeptide analysis 70:135 Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis. 34725484 3 48 theme Glycoproteomics 397:411 arg1 Initiative 413:422 the HUPO Human Glycoproteomics Initiative 382:422 the HUPO Human Glycoproteomics Initiative 382:422 Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. 34725484 2 49 theme tandem 280:285 arg1 spectra 292:298 complex glycopeptide tandem mass spectra 259:298 complex glycopeptide tandem mass spectra 259:298 Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. 34725484 6 50 theme high-coverage 1054:1066 arg1 solutions 1112:1120 improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions 1044:1120 improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions 1044:1120 Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. 34725484 7 51 theme search 1262:1267 arg1 strategies 1269:1278 several high-performance search strategies 1237:1278 several high-performance search strategies 1237:1278 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 6 52 theme glycoproteomics 1089:1103 arg1 solutions 1112:1120 improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions 1044:1120 improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions 1044:1120 Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. 34725484 2 53 theme complex 259:265 arg1 spectra 292:298 complex glycopeptide tandem mass spectra 259:298 complex glycopeptide tandem mass spectra 259:298 Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. 34725484 2 54 theme glycopeptide 267:278 arg1 spectra 292:298 complex glycopeptide tandem mass spectra 259:298 complex glycopeptide tandem mass spectra 259:298 Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. 34725484 7 55 theme glycopeptide 1193:1204 arg1 analysis 1211:1218 comprehensive glycopeptide data analysis 1179:1218 comprehensive glycopeptide data analysis 1179:1218 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 6 56 theme search 1105:1110 arg1 solutions 1112:1120 improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions 1044:1120 improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions 1044:1120 Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. 34725484 7 57 theme data 1206:1209 arg1 analysis 1211:1218 comprehensive glycopeptide data analysis 1179:1218 comprehensive glycopeptide data analysis 1179:1218 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 1 58 theme powerful 159:166 arg1 Glycoproteomics 138:152 Glycoproteomics 138:152 Glycoproteomics 138:152 Glycoproteomics is a powerful yet analytically challenging research tool. 34725484 1 58 theme powerful 159:166 arg1 tool 206:209 a powerful yet analytically challenging research tool 157:209 a powerful yet analytically challenging research tool 157:209 Glycoproteomics is a powerful yet analytically challenging research tool. 34725484 5 59 theme high-performance 860:875 arg1 strategies 905:914 several high-performance glycoproteomics informatics strategies 852:914 several high-performance glycoproteomics informatics strategies 852:914 Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. 34725484 3 60 theme Human 391:395 arg1 Initiative 413:422 the HUPO Human Glycoproteomics Initiative 382:422 the HUPO Human Glycoproteomics Initiative 382:422 Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. 34725484 6 61 theme search 995:1000 arg1 parameters 1002:1011 key performance-associated search parameters 968:1011 key performance-associated search parameters 968:1011 Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. 34725484 7 62 theme comprehensive 1179:1191 arg1 analysis 1211:1218 comprehensive glycopeptide data analysis 1179:1218 comprehensive glycopeptide data analysis 1179:1218 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 4 63 theme O-glycopeptide 722:735 arg1 analysis 742:749 O-glycopeptide data analysis 722:749 O-glycopeptide data analysis 722:749 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 0 64 theme search 87:92 arg1 strategies 94:103 high-performance search strategies 70:103 high-performance search strategies for serum glycopeptide analysis 70:135 Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis. 34725484 4 65 theme spectrometrybased 586:602 arg1 datasets 620:627 The same mass spectrometrybased glycoproteomics datasets 572:627 The same mass spectrometrybased glycoproteomics datasets from human serum 572:644 The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. 34725484 2 66 gly glycopeptide 267:278 arg2 glycopeptide 267:278 complex glycopeptide tandem mass spectra 259:298 complex glycopeptide tandem mass spectra 259:298 Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. 34725484 7 67 theme software 1157:1164 arg1 packages 1166:1173 diverse software packages 1149:1173 diverse software packages for comprehensive glycopeptide data analysis 1149:1218 This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. 34725484 1 68 theme challenging 185:195 arg1 Glycoproteomics 138:152 Glycoproteomics 138:152 Glycoproteomics 138:152 Glycoproteomics is a powerful yet analytically challenging research tool. 34725484 1 68 theme challenging 185:195 arg1 tool 206:209 a powerful yet analytically challenging research tool 157:209 a powerful yet analytically challenging research tool 157:209 Glycoproteomics is a powerful yet analytically challenging research tool. 34725484 3 69 theme community 430:438 arg1 study 440:444 this community study 425:444 this community study 425:444 Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. 4054112 0 0 theme mucus 99:103 arg1 glycoproteins 105:117 mucus glycoproteins 99:117 mucus glycoproteins of human seminal plasma 99:141 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 5 1 theme Lewis 1142:1146 arg1 type 1154:1157 the Lewis blood type 1138:1157 the Lewis blood type of the respective donor 1138:1181 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 4 2 theme sialylated 872:881 arg1 saccharides 883:893 neutral and sialylated saccharides 860:893 neutral and sialylated saccharides related to the Lewis system 860:921 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 3 3 theme 1----2 670:675 arg1 [NeuAc 688:693 Fuc(1----2)Gal(1----4)[NeuAc(2----6) 666:701 Fuc(1----2)Gal(1----4)[NeuAc(2----6) 666:701 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 1 4 gly sialylated 181:190 arg1 alditols 203:210 four major sialylated saccharide alditols 170:210 four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma 170:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 3 5 from A6 553:554 arg1 isomers 518:524 isomers 518:524 isomers 518:524 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 1 6 theme major 175:179 arg1 alditols 203:210 four major sialylated saccharide alditols 170:210 four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma 170:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 5 7 theme Ca 1203:1204 arg1 19-9 1206:1209 Ca 19-9 1203:1209 Ca 19-9 activity of its seminal plasma 1203:1240 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 8 theme blood 1148:1152 arg1 type 1154:1157 the Lewis blood type 1138:1157 the Lewis blood type of the respective donor 1138:1181 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 4 9 theme Lewis 910:914 arg1 system 916:921 the Lewis system 906:921 the Lewis system 906:921 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 4 10 theme biosynthetic 834:845 arg1 pathways 847:854 the biosynthetic pathways 830:854 the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system 830:921 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 0 11 gly sialylated 71:80 arg1 saccharides 82:92 major sialylated saccharides 65:92 major sialylated saccharides 65:92 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 5 12 theme 19-9 1206:1209 arg1 activity 1211:1218 Ca 19-9 activity 1203:1218 Ca 19-9 activity of its seminal plasma 1203:1240 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 1 13 theme fast-atom-bombardment 289:309 arg1 spectrometry 316:327 fast-atom-bombardment mass spectrometry 289:327 fast-atom-bombardment mass spectrometry 289:327 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 3 14 theme terminal 593:600 arg1 sequences 602:610 terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1---- 593:714 terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1---- 593:714 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 1 15 theme mass 311:314 arg1 spectrometry 316:327 fast-atom-bombardment mass spectrometry 289:327 fast-atom-bombardment mass spectrometry 289:327 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 0 16 theme seminal 128:134 arg1 plasma 136:141 human seminal plasma 122:141 human seminal plasma 122:141 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 3 17 dep see 477:479 arg1 Formula 468:474 Formula 468:474 Formula 468:474 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 18 theme major 533:537 arg1 saccharide 539:548 the major saccharide 529:548 the major saccharide in A6 529:554 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 2 19 theme CrO3 451:454 arg1 oxidation 456:464 CrO3 oxidation 451:464 CrO3 oxidation 451:464 Anomeric configurations of the glycosidic bonds were determined by exoglycosidase digestion and CrO3 oxidation. 4054112 1 20 theme sialylated 181:190 arg1 alditols 203:210 four major sialylated saccharide alditols 170:210 four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma 170:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 0 21 theme human 122:126 arg1 plasma 136:141 human seminal plasma 122:141 human seminal plasma 122:141 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 5 22 theme respective 1166:1175 arg1 donor 1177:1181 the respective donor 1162:1181 the respective donor 1162:1181 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 1 23 theme saccharide 192:201 arg1 alditols 203:210 four major sialylated saccharide alditols 170:210 four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma 170:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 4 24 from chromatography 784:797 arg1 data 753:756 quantitative data 740:756 quantitative data from high-pressure liquid chromatography 740:797 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 4 25 theme structural 806:815 arg1 information 817:827 structural information 806:827 structural information 806:827 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 0 26 gly glycoproteins 105:117 arg1 glycoproteins 105:117 mucus glycoproteins 99:117 mucus glycoproteins of human seminal plasma 99:141 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 1 27 theme alditols 203:210 arg1 structures 156:165 The primary structures 144:165 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma 144:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 0 28 theme Primary 0:6 arg1 structures 8:17 Primary structures 0:17 Primary structures 0:17 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 1 29 gly glycoproteins 231:243 arg1 glycoproteins 231:243 mucus glycoproteins 225:243 mucus glycoproteins of human seminal plasma 225:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 3 30 from saccharide 539:548 arg1 A6 553:554 A6 553:554 A6 553:554 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 31 theme 2----3 618:623 arg1 [Fuc 636:639 NeuAc(2----3)Gal(1----4)[Fuc 612:639 terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1---- 593:714 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 31 theme 2----3 618:623 arg1 1----3 641:646 1----3 641:646 1----3 641:646 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 5 32 theme plasma 1235:1240 arg1 activity 1211:1218 Ca 19-9 activity 1203:1218 Ca 19-9 activity of its seminal plasma 1203:1240 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 0 33 theme Lewis 23:27 arg1 expression 51:60 Lewis blood-group-dependent expression 23:60 Lewis blood-group-dependent expression 23:60 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 5 34 theme antigenic 1036:1044 arg1 Ley 1070:1072 Ley 1070:1072 Ley 1070:1072 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 34 theme antigenic 1036:1044 arg1 determinants 1046:1057 antigenic determinants 1036:1057 antigenic determinants H, Lex and Ley 1036:1072 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 34 theme antigenic 1036:1044 arg1 Lex 1062:1064 Lex 1062:1064 Lex 1062:1064 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 34 theme antigenic 1036:1044 arg1 H 1059:1059 H 1059:1059 H 1059:1059 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 4 35 theme high-pressure 763:775 arg1 chromatography 784:797 high-pressure liquid chromatography 763:797 high-pressure liquid chromatography 763:797 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 2 36 theme Anomeric 355:362 arg1 configurations 364:377 Anomeric configurations 355:377 Anomeric configurations of the glycosidic bonds 355:401 Anomeric configurations of the glycosidic bonds were determined by exoglycosidase digestion and CrO3 oxidation. 4054112 1 37 theme methylation 333:343 arg1 analysis 345:352 methylation analysis 333:352 methylation analysis 333:352 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 0 38 theme plasma 136:141 arg1 glycoproteins 105:117 mucus glycoproteins 99:117 mucus glycoproteins of human seminal plasma 99:141 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 3 39 theme GlcNAc 649:654 arg1 GlcNAc 703:708 NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc 612:708 terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1---- 593:714 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 40 theme NeuAc 612:616 arg1 [Fuc 636:639 NeuAc(2----3)Gal(1----4)[Fuc 612:639 terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1---- 593:714 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 40 theme NeuAc 612:616 arg1 1----3 641:646 1----3 641:646 1----3 641:646 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 1 41 theme mucus 225:229 arg1 glycoproteins 231:243 mucus glycoproteins 225:243 mucus glycoproteins of human seminal plasma 225:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 5 42 theme donor 1177:1181 arg1 type 1154:1157 the Lewis blood type 1138:1157 the Lewis blood type of the respective donor 1138:1181 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 43 theme asialo 988:993 arg1 counterparts 995:1006 their asialo counterparts 982:1006 their asialo counterparts 982:1006 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 44 theme seminal 1227:1233 arg1 plasma 1235:1240 its seminal plasma 1223:1240 its seminal plasma 1223:1240 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 45 dep saccharides 952:962 arg1 A8 975:976 A8 975:976 A8 975:976 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 45 dep saccharides 952:962 arg1 saccharides 952:962 saccharides A6, A7 and A8 and their asialo counterparts 952:1006 saccharides 952:962 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 45 dep saccharides 952:962 arg1 A7 968:969 A7 968:969 A7 968:969 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 0 46 theme blood-group-dependent 29:49 arg1 expression 51:60 Lewis blood-group-dependent expression 23:60 Lewis blood-group-dependent expression 23:60 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 3 47 dep GlcNAc 649:654 arg1 [NeuAc 688:693 Fuc(1----2)Gal(1----4)[NeuAc(2----6) 666:701 Fuc(1----2)Gal(1----4)[NeuAc(2----6) 666:701 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 47 dep GlcNAc 649:654 arg1 1---- 656:660 1---- 656:660 1---- 656:660 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 4 48 theme related 895:901 arg1 saccharides 883:893 neutral and sialylated saccharides 860:893 neutral and sialylated saccharides related to the Lewis system 860:921 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 1 49 attach derived 212:218 arg1 glycoproteins 231:243 mucus glycoproteins 225:243 mucus glycoproteins of human seminal plasma 225:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 1 49 attach derived 212:218 arg2 alditols 203:210 four major sialylated saccharide alditols 170:210 four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma 170:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 3 50 theme 1----4 629:634 arg1 [Fuc 636:639 NeuAc(2----3)Gal(1----4)[Fuc 612:639 terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1---- 593:714 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 50 theme 1----4 629:634 arg1 1----3 641:646 1----3 641:646 1----3 641:646 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 0 51 theme major 65:69 arg1 saccharides 82:92 major sialylated saccharides 65:92 major sialylated saccharides 65:92 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 5 52 theme counterparts 995:1006 arg1 Expression 938:947 Expression 938:947 Expression 938:947 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 4 53 theme liquid 777:782 arg1 chromatography 784:797 high-pressure liquid chromatography 763:797 high-pressure liquid chromatography 763:797 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 3 54 theme saccharide 539:548 arg1 isomers 518:524 isomers 518:524 isomers 518:524 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 4 55 gly sialylated 872:881 arg1 saccharides 883:893 neutral and sialylated saccharides 860:893 neutral and sialylated saccharides related to the Lewis system 860:921 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 3 56 theme Fuc 666:668 arg1 [NeuAc 688:693 Fuc(1----2)Gal(1----4)[NeuAc(2----6) 666:701 Fuc(1----2)Gal(1----4)[NeuAc(2----6) 666:701 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 57 theme Gal 625:627 arg1 [Fuc 636:639 NeuAc(2----3)Gal(1----4)[Fuc 612:639 terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1---- 593:714 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 57 theme Gal 625:627 arg1 1----3 641:646 1----3 641:646 1----3 641:646 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 58 from isomers 518:524 arg1 A6 553:554 A6 553:554 A6 553:554 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 2 59 theme bonds 397:401 arg1 configurations 364:377 Anomeric configurations 355:377 Anomeric configurations of the glycosidic bonds 355:401 Anomeric configurations of the glycosidic bonds were determined by exoglycosidase digestion and CrO3 oxidation. 4054112 5 60 theme saccharides 952:962 arg1 Expression 938:947 Expression 938:947 Expression 938:947 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 3 61 dep components 497:506 arg1 see 477:479 see 477:479 see text 477:484 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 2 62 theme glycosidic 386:395 arg1 bonds 397:401 the glycosidic bonds 382:401 the glycosidic bonds 382:401 Anomeric configurations of the glycosidic bonds were determined by exoglycosidase digestion and CrO3 oxidation. 4054112 1 63 theme human 248:252 arg1 plasma 262:267 human seminal plasma 248:267 human seminal plasma 248:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 4 64 theme neutral 860:866 arg1 saccharides 883:893 neutral and sialylated saccharides 860:893 neutral and sialylated saccharides related to the Lewis system 860:921 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 5 65 dep determinants 1046:1057 arg1 Ley 1070:1072 Ley 1070:1072 Ley 1070:1072 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 65 dep determinants 1046:1057 arg1 determinants 1046:1057 antigenic determinants 1036:1057 antigenic determinants H, Lex and Ley 1036:1072 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 65 dep determinants 1046:1057 arg1 Lex 1062:1064 Lex 1062:1064 Lex 1062:1064 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 5 65 dep determinants 1046:1057 arg1 H 1059:1059 H 1059:1059 H 1059:1059 Expression of saccharides A6, A7 and A8 and their asialo counterparts, which are characterized by antigenic determinants H, Lex and Ley, respectively, is qualitatively and quantitatively dependent on the Lewis blood type of the respective donor and correlates with Ca 19-9 activity of its seminal plasma. 4054112 1 66 theme primary 148:154 arg1 structures 156:165 The primary structures 144:165 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma 144:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 1 67 theme seminal 254:260 arg1 plasma 262:267 human seminal plasma 248:267 human seminal plasma 248:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 0 68 theme saccharides 82:92 arg1 expression 51:60 Lewis blood-group-dependent expression 23:60 Lewis blood-group-dependent expression 23:60 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 0 68 theme saccharides 82:92 arg1 structures 8:17 Primary structures 0:17 Primary structures 0:17 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 0 69 from glycoproteins 105:117 arg1 expression 51:60 Lewis blood-group-dependent expression 23:60 Lewis blood-group-dependent expression 23:60 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 0 69 from glycoproteins 105:117 arg1 structures 8:17 Primary structures 0:17 Primary structures 0:17 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 4 70 theme quantitative 740:751 arg1 data 753:756 quantitative data 740:756 quantitative data from high-pressure liquid chromatography 740:797 Based on quantitative data from high-pressure liquid chromatography and on structural information, the biosynthetic pathways for neutral and sialylated saccharides related to the Lewis system were proposed. 4054112 3 71 dep sequences 602:610 arg1 GlcNAc 703:708 NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc 612:708 terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1---- 593:714 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 72 theme minor 491:495 arg1 components 497:506 Two minor components 487:506 (Formula: see text) Two minor components 467:506 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 1 73 theme plasma 262:267 arg1 glycoproteins 231:243 mucus glycoproteins 225:243 mucus glycoproteins of human seminal plasma 225:267 The primary structures of four major sialylated saccharide alditols derived from mucus glycoproteins of human seminal plasma were established by fast-atom-bombardment mass spectrometry and methylation analysis. 4054112 0 74 theme sialylated 71:80 arg1 saccharides 82:92 major sialylated saccharides 65:92 major sialylated saccharides 65:92 Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. 4054112 3 75 theme Gal 677:679 arg1 [NeuAc 688:693 Fuc(1----2)Gal(1----4)[NeuAc(2----6) 666:701 Fuc(1----2)Gal(1----4)[NeuAc(2----6) 666:701 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 3 76 theme [Fuc 636:639 arg1 GlcNAc 649:654 NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc 612:654 terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1---- 593:714 (Formula: see text) Two minor components represent isomers of the major saccharide in A6, which are probably characterized by terminal sequences NeuAc(2----3)Gal(1----4)[Fuc(1----3)]GlcNAc(1---- and Fuc(1----2)Gal(1----4)[NeuAc(2----6)]GlcNAc(1----, respectively. 4054112 2 77 theme exoglycosidase 422:435 arg1 digestion 437:445 exoglycosidase digestion 422:445 exoglycosidase digestion 422:445 Anomeric configurations of the glycosidic bonds were determined by exoglycosidase digestion and CrO3 oxidation. 3191924 1 0 gly glycoproteins 230:242 arg1 glycoproteins 230:242 the respiratory-mucus glycoproteins 208:242 the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome 208:314 The carbohydrate chains of the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome were released by alkaline borohydride treatment. 3191924 0 1 theme respiratory-mucus 105:121 arg1 glycoproteins 123:135 respiratory-mucus glycoproteins 105:135 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 105:178 Isolation and structural characterization of low-molecular-mass monosialyl oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis. 3191924 10 2 theme acid 1285:1288 arg1 residue 1290:1296 The sialic acid residue 1274:1296 The sialic acid residue 1274:1296 The sialic acid residue was found to occur either in alpha (2----3)- or alpha (2----6)-linkage to a galactosyl residue or in alpha (2----6)-linkage to GalNAc-ol. 3191924 5 3 theme A. 1172:1173 arg1 mucus 1142:1146 the bronchial mucus 1128:1146 the bronchial mucus of this patient [Klein, A. et al. (1988) Eur 1128:1191 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 5 4 dep see 987:989 arg1 formula 978:984 formula 978:984 formula 978:984 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 3 5 theme oligosaccharidealditols 693:715 arg1 structures 675:684 The structures 671:684 The structures of the oligosaccharidealditols 671:715 The structures of the oligosaccharidealditols were determined by 500-MHz 1H-NMR spectroscopy in combination with sugar composition analysis. 3191924 10 6 theme sialic 1278:1283 arg1 residue 1290:1296 The sialic acid residue 1274:1296 The sialic acid residue 1274:1296 The sialic acid residue was found to occur either in alpha (2----3)- or alpha (2----6)-linkage to a galactosyl residue or in alpha (2----6)-linkage to GalNAc-ol. 3191924 8 7 theme J 1248:1248 arg1 Biochem 1250:1256 J Biochem 1248:1256 J Biochem. 1248:1257 J Biochem. 3191924 10 8 theme 2----6 1406:1411 arg1 -linkage 1413:1420 alpha (2----6)-linkage 1399:1420 alpha (2----6)-linkage to GalNAc-ol 1399:1433 The sialic acid residue was found to occur either in alpha (2----3)- or alpha (2----6)-linkage to a galactosyl residue or in alpha (2----6)-linkage to GalNAc-ol. 3191924 4 9 from range 842:846 arg1 size 851:854 size 851:854 size 851:854 The 24 structures established range in size from disaccharides to heptasaccharides. 3191924 5 10 theme oligosaccharides 1021:1036 arg1 oligosaccharides 1021:1036 the 24 monosialyl oligosaccharides 1003:1036 the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur 1003:1191 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 5 10 theme oligosaccharides 1021:1036 arg1 23 997:998 23 997:998 23 997:998 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 1 11 theme respiratory-mucus 212:228 arg1 glycoproteins 230:242 the respiratory-mucus glycoproteins 208:242 the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome 208:314 The carbohydrate chains of the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome were released by alkaline borohydride treatment. 3191924 0 12 theme patient 142:148 arg1 glycoproteins 123:135 respiratory-mucus glycoproteins 105:135 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 105:178 Isolation and structural characterization of low-molecular-mass monosialyl oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis. 3191924 0 13 theme low-molecular-mass 45:62 arg1 monosialyl 64:73 low-molecular-mass monosialyl 45:73 low-molecular-mass monosialyl 45:73 Isolation and structural characterization of low-molecular-mass monosialyl oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis. 3191924 0 14 gly glycoproteins 123:135 arg1 glycoproteins 123:135 respiratory-mucus glycoproteins 105:135 respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 105:178 Isolation and structural characterization of low-molecular-mass monosialyl oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis. 3191924 1 15 theme glycoproteins 230:242 arg1 chains 198:203 The carbohydrate chains 181:203 The carbohydrate chains of the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome 181:314 The carbohydrate chains of the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome were released by alkaline borohydride treatment. 3191924 2 16 theme alkylamine 579:588 arg1 column 590:595 a silica-based alkylamine column 564:595 a silica-based alkylamine column 564:595 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 7 17 dep 631-642 1211:1217 arg1 Eur 1243:1245 Eur 1243:1245 Eur 1243:1245 171, 631-642; Breg, J. et al. (1988) Eur. 3191924 7 17 dep 631-642 1211:1217 arg1 1988 1237:1240 1988 1237:1240 1988 1237:1240 171, 631-642; Breg, J. et al. (1988) Eur. 3191924 7 17 dep 631-642 1211:1217 arg1 J. 1226:1227 J. 1226:1227 J. 1226:1227 171, 631-642; Breg, J. et al. (1988) Eur. 3191924 5 18 theme bronchiectasis 937:950 arg1 glycoproteins 958:970 the bronchiectasis mucus glycoproteins 933:970 the bronchiectasis mucus glycoproteins 933:970 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 2 19 theme straight-phase 500:513 arg1 HPLC 555:558 HPLC 555:558 HPLC 555:558 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 2 19 theme straight-phase 500:513 arg1 chromatography 539:552 consecutive straight-phase high-performance liquid chromatography 488:552 consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column 488:595 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 2 20 theme silica-based 566:577 arg1 column 590:595 a silica-based alkylamine column 564:595 a silica-based alkylamine column 564:595 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 1 21 theme alkaline 333:340 arg1 treatment 354:362 alkaline borohydride treatment 333:362 alkaline borohydride treatment 333:362 The carbohydrate chains of the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome were released by alkaline borohydride treatment. 3191924 2 22 theme consecutive 488:498 arg1 HPLC 555:558 HPLC 555:558 HPLC 555:558 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 2 22 theme consecutive 488:498 arg1 chromatography 539:552 consecutive straight-phase high-performance liquid chromatography 488:552 consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column 488:595 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 1 23 theme borohydride 342:352 arg1 treatment 354:362 alkaline borohydride treatment 333:362 alkaline borohydride treatment 333:362 The carbohydrate chains of the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome were released by alkaline borohydride treatment. 3191924 5 24 theme bronchial 1132:1140 arg1 mucus 1142:1146 the bronchial mucus 1128:1146 the bronchial mucus of this patient [Klein, A. et al. (1988) Eur 1128:1191 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 3 25 theme 1H-NMR 744:749 arg1 spectroscopy 751:762 500-MHz 1H-NMR spectroscopy 736:762 500-MHz 1H-NMR spectroscopy 736:762 The structures of the oligosaccharidealditols were determined by 500-MHz 1H-NMR spectroscopy in combination with sugar composition analysis. 3191924 1 26 theme patient 249:255 arg1 glycoproteins 230:242 the respiratory-mucus glycoproteins 208:242 the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome 208:314 The carbohydrate chains of the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome were released by alkaline borohydride treatment. 3191924 0 27 theme structural 14:23 arg1 characterization 25:40 structural characterization 14:40 structural characterization 14:40 Isolation and structural characterization of low-molecular-mass monosialyl oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis. 3191924 7 28 dep J. 1226:1227 arg1 al 1232:1233 et al 1229:1233 631-642; Breg, J. et al. (1988) Eur 1211:1245 171, 631-642; Breg, J. et al. (1988) Eur. 3191924 2 29 theme Low-molecular-mass 365:382 arg1 oligosaccharide-alditols 396:419 Low-molecular-mass, monosialyl oligosaccharide-alditols 365:419 Low-molecular-mass, monosialyl oligosaccharide-alditols 365:419 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 2 30 theme reverse-phase 602:614 arg1 HPLC 616:619 reverse-phase HPLC 602:619 reverse-phase HPLC 602:619 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 2 31 from HPLC 616:619 arg1 column 590:595 a silica-based alkylamine column 564:595 a silica-based alkylamine column 564:595 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 0 32 dep oligosaccharides 75:90 arg1 derived 92:98 derived 92:98 oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis 75:178 Isolation and structural characterization of low-molecular-mass monosialyl oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis. 3191924 2 33 theme liquid 532:537 arg1 HPLC 555:558 HPLC 555:558 HPLC 555:558 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 2 33 theme liquid 532:537 arg1 chromatography 539:552 consecutive straight-phase high-performance liquid chromatography 488:552 consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column 488:595 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 5 34 theme Novel 896:900 arg1 oligosaccharides 902:917 Novel oligosaccharides 896:917 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins 896:970 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 3 35 theme composition 790:800 arg1 analysis 802:809 sugar composition analysis 784:809 sugar composition analysis 784:809 The structures of the oligosaccharidealditols were determined by 500-MHz 1H-NMR spectroscopy in combination with sugar composition analysis. 3191924 10 36 theme galactosyl 1374:1383 arg1 residue 1385:1391 a galactosyl residue 1372:1391 a galactosyl residue 1372:1391 The sialic acid residue was found to occur either in alpha (2----3)- or alpha (2----6)-linkage to a galactosyl residue or in alpha (2----6)-linkage to GalNAc-ol. 3191924 2 37 theme octadecyl 639:647 arg1 column 649:654 a silica-based octadecyl column 624:654 a silica-based octadecyl column 624:654 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 5 38 theme mucus 952:956 arg1 glycoproteins 958:970 the bronchiectasis mucus glycoproteins 933:970 the bronchiectasis mucus glycoproteins 933:970 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 2 39 theme anion-exchange 438:451 arg1 chromatography 453:466 anion-exchange chromatography 438:466 anion-exchange chromatography 438:466 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 0 40 theme monosialyl 64:73 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and structural characterization of low-molecular-mass monosialyl oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis. 3191924 0 40 theme monosialyl 64:73 arg1 characterization 25:40 structural characterization 14:40 structural characterization 14:40 Isolation and structural characterization of low-molecular-mass monosialyl oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis. 3191924 3 41 theme 500-MHz 736:742 arg1 spectroscopy 751:762 500-MHz 1H-NMR spectroscopy 736:762 500-MHz 1H-NMR spectroscopy 736:762 The structures of the oligosaccharidealditols were determined by 500-MHz 1H-NMR spectroscopy in combination with sugar composition analysis. 3191924 5 42 theme neutral 1089:1095 arg1 oligosaccharides 1097:1112 neutral oligosaccharides 1089:1112 neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur 1089:1191 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 10 43 theme -linkage 1360:1367 arg1 alpha 1327:1331 alpha (2----3)- 1327:1341 alpha (2----3)- 1327:1341 The sialic acid residue was found to occur either in alpha (2----3)- or alpha (2----6)-linkage to a galactosyl residue or in alpha (2----6)-linkage to GalNAc-ol. 3191924 5 44 theme oligosaccharides 1097:1112 arg1 extensions 1075:1084 extensions 1075:1084 extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur 1075:1191 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 5 45 dep A. 1172:1173 arg1 al 1178:1179 this patient [Klein, A. et al 1151:1179 al 1178:1179 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 5 46 gly glycoproteins 958:970 arg1 glycoproteins 958:970 the bronchiectasis mucus glycoproteins 933:970 the bronchiectasis mucus glycoproteins 933:970 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 3 47 theme sugar 784:788 arg1 analysis 802:809 sugar composition analysis 784:809 sugar composition analysis 784:809 The structures of the oligosaccharidealditols were determined by 500-MHz 1H-NMR spectroscopy in combination with sugar composition analysis. 3191924 10 48 theme alpha 1399:1403 arg1 -linkage 1413:1420 alpha (2----6)-linkage 1399:1420 alpha (2----6)-linkage to GalNAc-ol 1399:1433 The sialic acid residue was found to occur either in alpha (2----3)- or alpha (2----6)-linkage to a galactosyl residue or in alpha (2----6)-linkage to GalNAc-ol. 3191924 2 49 theme silica-based 626:637 arg1 column 649:654 a silica-based octadecyl column 624:654 a silica-based octadecyl column 624:654 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 5 50 theme monosialyl 1010:1019 arg1 oligosaccharides 1021:1036 the 24 monosialyl oligosaccharides 1003:1036 the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur 1003:1191 Novel oligosaccharides obtained from the bronchiectasis mucus glycoproteins are: (formula; see text) 23 of the 24 monosialyl oligosaccharides characterized can be conceived of as extensions of neutral oligosaccharides purified from the bronchial mucus of this patient [Klein, A. et al. (1988) Eur. 3191924 2 51 from chromatography 539:552 arg1 column 590:595 a silica-based alkylamine column 564:595 a silica-based alkylamine column 564:595 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 1 52 theme carbohydrate 185:196 arg1 chains 198:203 The carbohydrate chains 181:203 The carbohydrate chains of the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome 181:314 The carbohydrate chains of the respiratory-mucus glycoproteins of a patient suffering from bronchiectasis due to Kartagener's syndrome were released by alkaline borohydride treatment. 3191924 2 53 theme high-performance 515:530 arg1 HPLC 555:558 HPLC 555:558 HPLC 555:558 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 2 53 theme high-performance 515:530 arg1 chromatography 539:552 consecutive straight-phase high-performance liquid chromatography 488:552 consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column 488:595 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by consecutive straight-phase high-performance liquid chromatography (HPLC) on a silica-based alkylamine column, and reverse-phase HPLC on a silica-based octadecyl column, respectively. 3191924 3 54 with combination 767:777 arg1 analysis 802:809 sugar composition analysis 784:809 sugar composition analysis 784:809 The structures of the oligosaccharidealditols were determined by 500-MHz 1H-NMR spectroscopy in combination with sugar composition analysis. 3855417 2 0 theme acid-containing 394:408 arg1 chains 410:415 neutral and sialic acid-containing chains 375:415 neutral and sialic acid-containing chains 375:415 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 1 1 theme normal 275:280 arg1 individual 282:291 a normal individual 273:291 a normal individual with that from one with cystic fibrosis 273:331 Studies were begun to compare the oligosaccharide structures of the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis. 3855417 5 2 theme GalB1,3 801:807 arg1 GalNAc 809:814 GlcNAcB1,6(GalB1,3)GalNAc 790:814 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc 755:814 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 0 3 from structures 16:25 arg1 individual 84:93 a normal individual 75:93 a normal individual 75:93 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual and one with cystic fibrosis. 3855417 1 4 theme oligosaccharide 159:173 arg1 structures 175:184 the oligosaccharide structures 155:184 the oligosaccharide structures of the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis 155:331 Studies were begun to compare the oligosaccharide structures of the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis. 3855417 1 5 theme individual 282:291 arg1 saliva 263:268 the submandibular-sublingual saliva 234:268 the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis 234:331 Studies were begun to compare the oligosaccharide structures of the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis. 3855417 5 6 dep GalB1,4 881:887 arg1 alpha 920:924 NeuAc alpha 2,3GalB1,3 914:935 NeuAc alpha 2,3GalB1,3 914:935 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 6 dep GalB1,4 881:887 arg1 GalNAc 937:942 GalNAc 937:942 GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc 881:942 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 6 dep GalB1,4 881:887 arg1 GlcNAcB1,6 903:912 GlcNAcB1,6 903:912 GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc 881:942 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 7 theme Fuc 776:778 arg1 1,3 786:788 Fuc alpha 1,3 776:788 Fuc alpha 1,3 776:788 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 7 theme Fuc 776:778 arg1 alpha 759:763 Fuc alpha 1,2GalB1,4 755:774 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc 755:814 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 6 8 theme sialic 1093:1098 arg1 units 1116:1120 the neutral and sialic acid-containing units 1077:1120 the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples 1077:1174 There were no apparent qualitative differences in the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples. 3855417 5 9 theme alpha 780:784 arg1 1,3 786:788 Fuc alpha 1,3 776:788 Fuc alpha 1,3 776:788 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 9 theme alpha 780:784 arg1 alpha 759:763 Fuc alpha 1,2GalB1,4 755:774 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc 755:814 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 0 10 theme cystic 108:113 arg1 fibrosis 115:122 cystic fibrosis 108:122 cystic fibrosis 108:122 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual and one with cystic fibrosis. 3855417 5 11 theme Fuc 889:891 arg1 1,3 899:901 Fuc alpha 1,3 889:901 Fuc alpha 1,3 889:901 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 11 theme Fuc 889:891 arg1 GalB1,4 881:887 GalB1,4 881:887 GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc 881:942 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 12 theme Fuc 827:829 arg1 alpha 759:763 Fuc alpha 1,2GalB1,4 755:774 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc 755:814 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 12 theme Fuc 827:829 arg1 1,3 837:839 Fuc alpha 1,3 827:839 Fuc alpha 1,3 827:839 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 4 13 theme alpha 704:708 arg1 2,3GalB1 710:717 NeuAc alpha 2,3GalB1 698:717 NeuAc alpha 2,3GalB1 698:717 Approximately 80% of the oligosaccharides were GalB1, 3GalNAc; Fuc alpha 1,2GalB1,3GalNAc; and NeuAc alpha 2,3GalB1, 3GalNAc. 3855417 5 14 theme alpha 974:978 arg1 1,3 980:982 Fuc alpha 1,3 970:982 Fuc alpha 1,3 970:982 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 14 theme alpha 974:978 arg1 alpha 953:957 Fuc alpha 1,2GalB1,4 949:968 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3) 949:1018 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 6 15 theme acid-containing 1100:1114 arg1 units 1116:1120 the neutral and sialic acid-containing units 1077:1120 the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples 1077:1174 There were no apparent qualitative differences in the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples. 3855417 5 16 dep alpha 759:763 arg1 GAlNAc 873:878 GAlNAc 873:878 GAlNAc 873:878 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 16 dep alpha 759:763 arg1 GalNAc 1019:1024 GalNAc 1019:1024 GalNAc 1019:1024 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 16 dep alpha 759:763 arg1 GalNAc 809:814 GlcNAcB1,6(GalB1,3)GalNAc 790:814 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc 755:814 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 16 dep alpha 759:763 arg1 GlcNAcB1,6 841:850 GlcNAcB1,6 841:850 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3) 755:872 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 2 17 theme alkaline/borotritide 344:363 arg1 cleavage 365:372 alkaline/borotritide cleavage 344:372 alkaline/borotritide cleavage 344:372 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 4 18 theme NeuAc 698:702 arg1 2,3GalB1 710:717 NeuAc alpha 2,3GalB1 698:717 NeuAc alpha 2,3GalB1 698:717 Approximately 80% of the oligosaccharides were GalB1, 3GalNAc; Fuc alpha 1,2GalB1,3GalNAc; and NeuAc alpha 2,3GalB1, 3GalNAc. 3855417 0 19 theme Oligosaccharide 0:14 arg1 structures 16:25 Oligosaccharide structures 0:25 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual 0:93 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual and one with cystic fibrosis. 3855417 5 20 theme NeuAc 914:918 arg1 alpha 920:924 NeuAc alpha 2,3GalB1,3 914:935 NeuAc alpha 2,3GalB1,3 914:935 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 20 theme NeuAc 914:918 arg1 GlcNAcB1,6 903:912 GlcNAcB1,6 903:912 GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc 881:942 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 1 21 theme low-molecular-weight 193:212 arg1 mucin 214:218 the low-molecular-weight mucin 189:218 the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis 189:331 Studies were begun to compare the oligosaccharide structures of the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis. 3855417 2 22 theme chromatography 473:486 arg1 combination 436:446 a combination 434:446 a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis 434:526 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 6 23 dep normal 1141:1146 arg1 samples 1168:1174 samples 1168:1174 samples 1168:1174 There were no apparent qualitative differences in the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples. 3855417 1 24 theme mucin 214:218 arg1 structures 175:184 the oligosaccharide structures 155:184 the oligosaccharide structures of the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis 155:331 Studies were begun to compare the oligosaccharide structures of the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis. 3855417 2 25 theme paper 467:471 arg1 chromatography 473:486 paper chromatography 467:486 paper chromatography 467:486 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 5 26 theme Fuc 755:757 arg1 structures 739:748 The other structures 729:748 The other structures 729:748 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 26 theme Fuc 755:757 arg1 alpha 759:763 Fuc alpha 1,2GalB1,4 755:774 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc 755:814 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 26 theme Fuc 755:757 arg1 alpha 856:860 Fuc alpha 1,2GalB1,3 852:871 Fuc alpha 1,2GalB1,3 852:871 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 26 theme Fuc 755:757 arg1 1,3 786:788 Fuc alpha 1,3 776:788 Fuc alpha 1,3 776:788 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 26 theme Fuc 755:757 arg1 1,3 837:839 Fuc alpha 1,3 827:839 Fuc alpha 1,3 827:839 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 2 27 theme sialic 387:392 arg1 chains 410:415 neutral and sialic acid-containing chains 375:415 neutral and sialic acid-containing chains 375:415 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 4 28 theme oligosaccharides 628:643 arg1 % 619:619 Approximately 80% 603:619 Approximately 80% of the oligosaccharides 603:643 Approximately 80% of the oligosaccharides were GalB1, 3GalNAc; Fuc alpha 1,2GalB1,3GalNAc; and NeuAc alpha 2,3GalB1, 3GalNAc. 3855417 4 28 theme oligosaccharides 628:643 arg1 oligosaccharides 628:643 the oligosaccharides 624:643 the oligosaccharides 624:643 Approximately 80% of the oligosaccharides were GalB1, 3GalNAc; Fuc alpha 1,2GalB1,3GalNAc; and NeuAc alpha 2,3GalB1, 3GalNAc. 3855417 2 29 theme filtration 455:464 arg1 combination 436:446 a combination 434:446 a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis 434:526 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 0 30 theme salivary 55:62 arg1 mucin 64:68 the low-molecular-weight salivary mucin 30:68 the low-molecular-weight salivary mucin from a normal individual 30:93 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual and one with cystic fibrosis. 3855417 1 31 theme cystic 317:322 arg1 fibrosis 324:331 cystic fibrosis 317:331 cystic fibrosis 317:331 Studies were begun to compare the oligosaccharide structures of the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis. 3855417 0 32 from individual 84:93 arg1 mucin 64:68 the low-molecular-weight salivary mucin 30:68 the low-molecular-weight salivary mucin from a normal individual 30:93 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual and one with cystic fibrosis. 3855417 0 32 from individual 84:93 arg1 structures 16:25 Oligosaccharide structures 0:25 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual 0:93 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual and one with cystic fibrosis. 3855417 5 33 theme Fuc 970:972 arg1 1,3 980:982 Fuc alpha 1,3 970:982 Fuc alpha 1,3 970:982 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 33 theme Fuc 970:972 arg1 alpha 953:957 Fuc alpha 1,2GalB1,4 949:968 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3) 949:1018 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 2 34 theme gel 451:453 arg1 filtration 455:464 gel filtration 451:464 gel filtration 451:464 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 0 35 theme low-molecular-weight 34:53 arg1 mucin 64:68 the low-molecular-weight salivary mucin 30:68 the low-molecular-weight salivary mucin from a normal individual 30:93 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual and one with cystic fibrosis. 3855417 2 36 theme electrophoresis 512:526 arg1 combination 436:446 a combination 434:446 a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis 434:526 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 5 37 theme alpha 831:835 arg1 alpha 759:763 Fuc alpha 1,2GalB1,4 755:774 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc 755:814 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 37 theme alpha 831:835 arg1 1,3 837:839 Fuc alpha 1,3 827:839 Fuc alpha 1,3 827:839 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 6 38 from differences 1062:1072 arg1 units 1116:1120 the neutral and sialic acid-containing units 1077:1120 the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples 1077:1174 There were no apparent qualitative differences in the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples. 3855417 5 39 theme Fuc 852:854 arg1 alpha 759:763 Fuc alpha 1,2GalB1,4 755:774 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc 755:814 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 39 theme Fuc 852:854 arg1 alpha 856:860 Fuc alpha 1,2GalB1,3 852:871 Fuc alpha 1,2GalB1,3 852:871 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 2 40 theme paper 506:510 arg1 electrophoresis 512:526 high-voltage paper electrophoresis 493:526 high-voltage paper electrophoresis 493:526 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 5 41 theme alpha 893:897 arg1 1,3 899:901 Fuc alpha 1,3 889:901 Fuc alpha 1,3 889:901 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 41 theme alpha 893:897 arg1 GalB1,4 881:887 GalB1,4 881:887 GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc 881:942 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 0 42 theme mucin 64:68 arg1 structures 16:25 Oligosaccharide structures 0:25 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual 0:93 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual and one with cystic fibrosis. 3855417 2 43 theme high-voltage 493:504 arg1 electrophoresis 512:526 high-voltage paper electrophoresis 493:526 high-voltage paper electrophoresis 493:526 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 2 44 theme neutral 375:381 arg1 chains 410:415 neutral and sialic acid-containing chains 375:415 neutral and sialic acid-containing chains 375:415 Following alkaline/borotritide cleavage, neutral and sialic acid-containing chains were purified by a combination of gel filtration, paper chromatography, and high-voltage paper electrophoresis. 3855417 5 45 theme other 733:737 arg1 structures 739:748 The other structures 729:748 The other structures 729:748 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 45 theme other 733:737 arg1 alpha 759:763 Fuc alpha 1,2GalB1,4 755:774 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc 755:814 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 46 theme Fuc 949:951 arg1 alpha 1002:1006 NeuAc alpha 2,3GalB1,3 996:1017 NeuAc alpha 2,3GalB1,3 996:1017 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 46 theme Fuc 949:951 arg1 1,3 980:982 Fuc alpha 1,3 970:982 Fuc alpha 1,3 970:982 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 46 theme Fuc 949:951 arg1 alpha 953:957 Fuc alpha 1,2GalB1,4 949:968 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3) 949:1018 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 1 47 with individual 282:291 arg1 that 298:301 that 298:301 that 298:301 Studies were begun to compare the oligosaccharide structures of the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis. 3855417 1 48 theme submandibular-sublingual 238:261 arg1 saliva 263:268 the submandibular-sublingual saliva 234:268 the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis 234:331 Studies were begun to compare the oligosaccharide structures of the low-molecular-weight mucin purified from the submandibular-sublingual saliva of a normal individual with that from one with cystic fibrosis. 3855417 5 49 theme NeuAc 996:1000 arg1 alpha 1002:1006 NeuAc alpha 2,3GalB1,3 996:1017 NeuAc alpha 2,3GalB1,3 996:1017 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 5 49 theme NeuAc 996:1000 arg1 alpha 953:957 Fuc alpha 1,2GalB1,4 949:968 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3) 949:1018 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 6 50 theme cystic 1152:1157 arg1 fibrosis 1159:1166 cystic fibrosis 1152:1166 cystic fibrosis 1152:1166 There were no apparent qualitative differences in the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples. 3855417 6 51 theme qualitative 1050:1060 arg1 differences 1062:1072 no apparent qualitative differences 1038:1072 no apparent qualitative differences in the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples 1038:1174 There were no apparent qualitative differences in the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples. 3855417 0 52 theme normal 77:82 arg1 individual 84:93 a normal individual 75:93 a normal individual 75:93 Oligosaccharide structures of the low-molecular-weight salivary mucin from a normal individual and one with cystic fibrosis. 3855417 5 53 dep alpha 953:957 arg1 GlcNAcB1,6 984:993 GlcNAcB1,6 984:993 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3) 949:1018 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 6 54 theme apparent 1041:1048 arg1 differences 1062:1072 no apparent qualitative differences 1038:1072 no apparent qualitative differences in the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples 1038:1174 There were no apparent qualitative differences in the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples. 3855417 4 55 theme alpha 670:674 arg1 1,2GalB1,3GalNAc 676:691 Fuc alpha 1,2GalB1,3GalNAc 666:691 Fuc alpha 1,2GalB1,3GalNAc 666:691 Approximately 80% of the oligosaccharides were GalB1, 3GalNAc; Fuc alpha 1,2GalB1,3GalNAc; and NeuAc alpha 2,3GalB1, 3GalNAc. 3855417 5 56 theme GlcNAcB1,6 790:799 arg1 GalNAc 809:814 GlcNAcB1,6(GalB1,3)GalNAc 790:814 Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc 755:814 The other structures were Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(GalB1,3)GalNAc or GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(Fuc alpha 1,2GalB1,3)GAlNAc; GalB1,4(Fuc alpha 1,3)GlcNAcB1,6(NeuAc alpha 2,3GalB1,3)GalNAc; and Fuc alpha 1,2GalB1,4(Fuc alpha 1,3)GlcNAcB1,6 (NeuAc alpha 2,3GalB1,3)GalNAc. 3855417 6 57 theme neutral 1081:1087 arg1 units 1116:1120 the neutral and sialic acid-containing units 1077:1120 the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples 1077:1174 There were no apparent qualitative differences in the neutral and sialic acid-containing units recovered from the normal and cystic fibrosis samples. 3855417 4 58 theme Fuc 666:668 arg1 1,2GalB1,3GalNAc 676:691 Fuc alpha 1,2GalB1,3GalNAc 666:691 Fuc alpha 1,2GalB1,3GalNAc 666:691 Approximately 80% of the oligosaccharides were GalB1, 3GalNAc; Fuc alpha 1,2GalB1,3GalNAc; and NeuAc alpha 2,3GalB1, 3GalNAc. 11294842 2 0 theme apo 382:384 arg1 concentrations 364:377 Elevated plasma concentrations 348:377 Elevated plasma concentrations of apo(a) and its fragments 348:405 Elevated plasma concentrations of apo(a) and its fragments may promote atherosclerosis, but the underlying mechanisms are incompletely understood. 11294842 7 1 from present 982:988 arg1 state 1024:1028 either a mono- or disialylated state 993:1028 state 1024:1028 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 4 2 theme -linked 646:652 arg1 oligosaccharides 677:692 the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides 635:692 the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a) 635:708 Here we have used exoglycosidase digestion and mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a). 11294842 8 3 theme non-sialylated 1193:1206 arg1 O-glycans 1208:1216 disialylated and non-sialylated O-glycans 1176:1216 disialylated and non-sialylated O-glycans 1176:1216 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 9 4 theme apo 1244:1246 arg1 O-glycans 1251:1259 apo(a) O-glycans 1244:1259 apo(a) O-glycans 1244:1259 Removal of apo(a) O-glycans by sialidase and O-glycosidase treatment dramatically increased the sensitivity of the polypeptide to thermolysin digestion. 11294842 2 5 theme fragments 397:405 arg1 concentrations 364:377 Elevated plasma concentrations 348:377 Elevated plasma concentrations of apo(a) and its fragments 348:405 Elevated plasma concentrations of apo(a) and its fragments may promote atherosclerosis, but the underlying mechanisms are incompletely understood. 11294842 4 6 used used 571:574 arg2 we 563:564 we 563:564 we 563:564 Here we have used exoglycosidase digestion and mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a). 11294842 8 7 theme smaller 1157:1163 arg1 amounts 1165:1171 smaller amounts 1157:1171 smaller amounts of disialylated and non-sialylated O-glycans 1157:1216 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 8 7 theme smaller 1157:1163 arg1 O-glycans 1208:1216 disialylated and non-sialylated O-glycans 1176:1216 disialylated and non-sialylated O-glycans 1176:1216 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 5 8 theme polypeptide 818:828 arg1 regions 803:809 thermolysin-sensitive regions 781:809 thermolysin-sensitive regions of the polypeptide 781:828 We also assessed the potential role of apo(a) O-glycans in protecting thermolysin-sensitive regions of the polypeptide. 11294842 10 9 theme first 1412:1416 arg1 data 1436:1439 the first direct sequencing data 1408:1439 the first direct sequencing data for apo(a) glycans 1408:1458 These studies provide the first direct sequencing data for apo(a) glycans and indicate a novel function for apo(a) O-glycans that is potentially related to the atherogenicity of Lp(a). 11294842 1 10 theme lipoprotein 286:296 arg1 particle 309:316 the lipoprotein(a) (Lp(a)) particle 282:316 the lipoprotein(a) (Lp(a)) particle 282:316 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 7 11 gly disialylated 1011:1022 arg1 state 1024:1028 either a mono- or disialylated state 993:1028 state 1024:1028 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 1 12 theme proteolytic 325:335 arg1 fragments 337:345 proteolytic fragments 325:345 proteolytic fragments 325:345 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 5 13 theme thermolysin-sensitive 781:801 arg1 regions 803:809 thermolysin-sensitive regions 781:809 thermolysin-sensitive regions of the polypeptide 781:828 We also assessed the potential role of apo(a) O-glycans in protecting thermolysin-sensitive regions of the polypeptide. 11294842 8 14 theme type 1102:1105 arg1 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 8 14 theme type 1102:1105 arg1 structure 1109:1117 the monosialylated core type 1 structure 1078:1117 the monosialylated core type 1 structure 1078:1117 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 7 15 theme mono- 1002:1006 arg1 state 1024:1028 either a mono- or disialylated state 993:1028 state 1024:1028 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 4 16 theme human 697:701 arg1 apo 703:705 human apo 697:705 human apo(a) 697:708 Here we have used exoglycosidase digestion and mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a). 11294842 4 16 theme human 697:701 arg1 a 707:707 a 707:707 a 707:707 Here we have used exoglycosidase digestion and mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a). 11294842 10 17 theme apo 1494:1496 arg1 O-glycans 1501:1509 apo(a) O-glycans 1494:1509 apo(a) O-glycans that is potentially related to the atherogenicity of Lp(a) 1494:1568 These studies provide the first direct sequencing data for apo(a) glycans and indicate a novel function for apo(a) O-glycans that is potentially related to the atherogenicity of Lp(a). 11294842 8 18 dep represented 1063:1073 arg1 % 1060:1060 80% 1058:1060 80% 1058:1060 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 10 19 theme novel 1475:1479 arg1 function 1481:1488 a novel function 1473:1488 a novel function for apo(a) O-glycans that is potentially related to the atherogenicity of Lp(a) 1473:1568 These studies provide the first direct sequencing data for apo(a) glycans and indicate a novel function for apo(a) O-glycans that is potentially related to the atherogenicity of Lp(a). 11294842 7 20 theme complex 951:957 arg1 structures 971:980 complex biantennary structures 951:980 complex biantennary structures present in either a mono- or disialylated state 951:1028 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 7 20 theme complex 951:957 arg1 N-glycans 936:944 The N-glycans 932:944 The N-glycans 932:944 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 7 21 theme disialylated 1011:1022 arg1 state 1024:1028 either a mono- or disialylated state 993:1028 state 1024:1028 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 6 22 contain contained 838:846 arg1 a 835:835 a 835:835 a 835:835 Apo(a) contained two major N-glycans that accounted for 17% of the total oligosaccharide structures. 11294842 6 22 contain contained 838:846 arg1 Apo 831:833 Apo 831:833 Apo(a) 831:836 Apo(a) contained two major N-glycans that accounted for 17% of the total oligosaccharide structures. 11294842 6 22 contain contained 838:846 arg2 N-glycans 858:866 two major N-glycans 848:866 two major N-glycans that accounted for 17% of the total oligosaccharide structures 848:929 Apo(a) contained two major N-glycans that accounted for 17% of the total oligosaccharide structures. 11294842 1 23 theme density 253:259 arg1 lipoprotein 261:271 low density lipoprotein 249:271 low density lipoprotein 249:271 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 10 24 theme apo 1445:1447 arg1 glycans 1452:1458 apo(a) glycans 1445:1458 apo(a) glycans 1445:1458 These studies provide the first direct sequencing data for apo(a) glycans and indicate a novel function for apo(a) O-glycans that is potentially related to the atherogenicity of Lp(a). 11294842 1 25 gly glycoprotein 180:191 arg1 Apolipoprotein 128:141 Apolipoprotein 128:141 Apolipoprotein(a) (apo(a)) 128:153 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 1 25 gly glycoprotein 180:191 arg1 glycoprotein 180:191 a multikringle domain glycoprotein 158:191 a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments 158:345 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 1 26 dep Apolipoprotein 128:141 arg1 a 151:151 a 151:151 a 151:151 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 1 26 dep Apolipoprotein 128:141 arg1 apo 147:149 apo 147:149 apo(a) 147:152 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 0 27 theme Structural 0:9 arg1 elucidation 11:21 Structural elucidation 0:21 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 0:126 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 4 28 theme apo 703:705 arg1 oligosaccharides 677:692 the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides 635:692 the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a) 635:708 Here we have used exoglycosidase digestion and mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a). 11294842 8 29 theme disialylated 1176:1187 arg1 O-glycans 1208:1216 disialylated and non-sialylated O-glycans 1176:1216 disialylated and non-sialylated O-glycans 1176:1216 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 9 30 theme polypeptide 1348:1358 arg1 sensitivity 1329:1339 the sensitivity 1325:1339 the sensitivity of the polypeptide to thermolysin digestion 1325:1383 Removal of apo(a) O-glycans by sialidase and O-glycosidase treatment dramatically increased the sensitivity of the polypeptide to thermolysin digestion. 11294842 7 31 theme present 982:988 arg1 structures 971:980 complex biantennary structures 951:980 complex biantennary structures present in either a mono- or disialylated state 951:1028 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 7 31 theme present 982:988 arg1 N-glycans 936:944 The N-glycans 932:944 The N-glycans 932:944 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 10 32 theme Lp 1564:1565 arg1 atherogenicity 1546:1559 the atherogenicity 1542:1559 the atherogenicity of Lp(a) 1542:1568 These studies provide the first direct sequencing data for apo(a) glycans and indicate a novel function for apo(a) O-glycans that is potentially related to the atherogenicity of Lp(a). 11294842 4 33 theme -linked 669:675 arg1 oligosaccharides 677:692 the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides 635:692 the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a) 635:708 Here we have used exoglycosidase digestion and mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a). 11294842 5 34 theme O-glycans 757:765 arg1 role 742:745 the potential role 728:745 the potential role of apo(a) O-glycans in protecting thermolysin-sensitive regions of the polypeptide 728:828 We also assessed the potential role of apo(a) O-glycans in protecting thermolysin-sensitive regions of the polypeptide. 11294842 10 35 theme sequencing 1425:1434 arg1 data 1436:1439 the first direct sequencing data 1408:1439 the first direct sequencing data for apo(a) glycans 1408:1458 These studies provide the first direct sequencing data for apo(a) glycans and indicate a novel function for apo(a) O-glycans that is potentially related to the atherogenicity of Lp(a). 11294842 1 36 theme apolipoprotein 226:239 arg1 B100 241:244 apolipoprotein B100 226:244 apolipoprotein B100 of low density lipoprotein 226:271 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 0 37 theme o-glycans 83:91 arg1 role 75:78 role 75:78 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 0:126 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 5 38 theme potential 732:740 arg1 role 742:745 the potential role 728:745 the potential role of apo(a) O-glycans in protecting thermolysin-sensitive regions of the polypeptide 728:828 We also assessed the potential role of apo(a) O-glycans in protecting thermolysin-sensitive regions of the polypeptide. 11294842 9 39 theme thermolysin 1363:1373 arg1 digestion 1375:1383 thermolysin digestion 1363:1383 thermolysin digestion 1363:1383 Removal of apo(a) O-glycans by sialidase and O-glycosidase treatment dramatically increased the sensitivity of the polypeptide to thermolysin digestion. 11294842 7 40 attach present 982:988 arg2 N-glycans 936:944 The N-glycans 932:944 The N-glycans 932:944 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 7 40 attach present 982:988 arg1 state 1024:1028 either a mono- or disialylated state 993:1028 state 1024:1028 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 7 40 attach present 982:988 arg2 structures 971:980 complex biantennary structures 951:980 complex biantennary structures present in either a mono- or disialylated state 951:1028 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 7 41 theme biantennary 959:969 arg1 structures 971:980 complex biantennary structures 951:980 complex biantennary structures present in either a mono- or disialylated state 951:1028 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 7 41 theme biantennary 959:969 arg1 N-glycans 936:944 The N-glycans 932:944 The N-glycans 932:944 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 8 42 theme monosialylated 1082:1095 arg1 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 8 42 theme monosialylated 1082:1095 arg1 structure 1109:1117 the monosialylated core type 1 structure 1078:1117 the monosialylated core type 1 structure 1078:1117 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 0 43 theme protease 107:114 arg1 resistance 116:125 protease resistance 107:125 protease resistance 107:125 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 6 44 theme major 852:856 arg1 N-glycans 858:866 two major N-glycans 848:866 two major N-glycans that accounted for 17% of the total oligosaccharide structures 848:929 Apo(a) contained two major N-glycans that accounted for 17% of the total oligosaccharide structures. 11294842 2 45 theme plasma 357:362 arg1 concentrations 364:377 Elevated plasma concentrations 348:377 Elevated plasma concentrations of apo(a) and its fragments 348:405 Elevated plasma concentrations of apo(a) and its fragments may promote atherosclerosis, but the underlying mechanisms are incompletely understood. 11294842 8 46 gly disialylated 1176:1187 arg1 O-glycans 1208:1216 disialylated and non-sialylated O-glycans 1176:1216 disialylated and non-sialylated O-glycans 1176:1216 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 0 47 theme N- 30:31 arg1 elucidation 11:21 Structural elucidation 0:21 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 0:126 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 9 48 dep sialidase 1264:1272 arg1 treatment 1292:1300 treatment 1292:1300 treatment 1292:1300 Removal of apo(a) O-glycans by sialidase and O-glycosidase treatment dramatically increased the sensitivity of the polypeptide to thermolysin digestion. 11294842 4 49 link -linked 646:652 arg1 oligosaccharides 677:692 the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides 635:692 the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a) 635:708 Here we have used exoglycosidase digestion and mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a). 11294842 2 50 theme Elevated 348:355 arg1 concentrations 364:377 Elevated plasma concentrations 348:377 Elevated plasma concentrations of apo(a) and its fragments 348:405 Elevated plasma concentrations of apo(a) and its fragments may promote atherosclerosis, but the underlying mechanisms are incompletely understood. 11294842 1 51 theme low 249:251 arg1 lipoprotein 261:271 low density lipoprotein 249:271 low density lipoprotein 249:271 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 10 52 theme direct 1418:1423 arg1 data 1436:1439 the first direct sequencing data 1408:1439 the first direct sequencing data for apo(a) glycans 1408:1458 These studies provide the first direct sequencing data for apo(a) glycans and indicate a novel function for apo(a) O-glycans that is potentially related to the atherogenicity of Lp(a). 11294842 7 53 from state 1024:1028 arg1 present 982:988 present 982:988 present 982:988 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 8 54 theme core 1097:1100 arg1 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 8 54 theme core 1097:1100 arg1 structure 1109:1117 the monosialylated core type 1 structure 1078:1117 the monosialylated core type 1 structure 1078:1117 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 0 55 theme O-glycans 37:45 arg1 elucidation 11:21 Structural elucidation 0:21 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 0:126 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 1 56 dep lipoprotein 286:296 arg1 a 305:305 a 305:305 a 305:305 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 1 56 dep lipoprotein 286:296 arg1 Lp 302:303 Lp 302:303 Lp(a) 302:306 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 2 57 theme underlying 444:453 arg1 mechanisms 455:464 the underlying mechanisms 440:464 the underlying mechanisms 440:464 Elevated plasma concentrations of apo(a) and its fragments may promote atherosclerosis, but the underlying mechanisms are incompletely understood. 11294842 1 58 dep exists 198:203 arg1 linked 216:221 linked 216:221 linked 216:221 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 0 59 dep N- 30:31 arg1 the 26:28 the 26:28 the 26:28 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 4 60 theme exoglycosidase 576:589 arg1 digestion 591:599 exoglycosidase digestion 576:599 exoglycosidase digestion 576:599 Here we have used exoglycosidase digestion and mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a). 11294842 1 61 theme lipoprotein 261:271 arg1 B100 241:244 apolipoprotein B100 226:244 apolipoprotein B100 of low density lipoprotein 226:271 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 8 62 gly non-sialylated 1193:1206 arg1 O-glycans 1208:1216 disialylated and non-sialylated O-glycans 1176:1216 disialylated and non-sialylated O-glycans 1176:1216 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 4 63 theme mass 605:608 arg1 spectrometry 610:621 mass spectrometry 605:621 mass spectrometry 605:621 Here we have used exoglycosidase digestion and mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a). 11294842 8 64 theme O-glycans 1208:1216 arg1 amounts 1165:1171 smaller amounts 1157:1171 smaller amounts of disialylated and non-sialylated O-glycans 1157:1216 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 8 64 theme O-glycans 1208:1216 arg1 O-glycans 1208:1216 disialylated and non-sialylated O-glycans 1176:1216 disialylated and non-sialylated O-glycans 1176:1216 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 9 65 theme O-glycans 1251:1259 arg1 Removal 1233:1239 Removal 1233:1239 Removal of apo(a) O-glycans by sialidase and O-glycosidase treatment 1233:1300 Removal of apo(a) O-glycans by sialidase and O-glycosidase treatment dramatically increased the sensitivity of the polypeptide to thermolysin digestion. 11294842 7 66 dep state 1024:1028 arg1 either 993:998 either 993:998 either 993:998 The N-glycans were complex biantennary structures present in either a mono- or disialylated state. 11294842 3 67 theme apo 519:521 arg1 proteolysis 526:536 apo(a) proteolysis 519:536 apo(a) proteolysis 519:536 The factors influencing apo(a) proteolysis are also uncertain. 11294842 6 68 theme structures 920:929 arg1 structures 920:929 the total oligosaccharide structures 894:929 the total oligosaccharide structures 894:929 Apo(a) contained two major N-glycans that accounted for 17% of the total oligosaccharide structures. 11294842 6 68 theme structures 920:929 arg1 % 889:889 17% 887:889 17% of the total oligosaccharide structures 887:929 Apo(a) contained two major N-glycans that accounted for 17% of the total oligosaccharide structures. 11294842 5 69 theme apo 750:752 arg1 O-glycans 757:765 apo(a) O-glycans 750:765 apo(a) O-glycans 750:765 We also assessed the potential role of apo(a) O-glycans in protecting thermolysin-sensitive regions of the polypeptide. 11294842 0 70 theme apolipoprotein 56:69 arg1 O-glycans 37:45 O-glycans 37:45 O-glycans 37:45 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 0 70 theme apolipoprotein 56:69 arg1 N- 30:31 N- 30:31 N- 30:31 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 0 71 dep elucidation 11:21 arg1 role 75:78 role 75:78 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 0:126 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 6 72 theme oligosaccharide 904:918 arg1 structures 920:929 the total oligosaccharide structures 894:929 the total oligosaccharide structures 894:929 Apo(a) contained two major N-glycans that accounted for 17% of the total oligosaccharide structures. 11294842 4 73 link -linked 669:675 arg1 oligosaccharides 677:692 the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides 635:692 the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a) 635:708 Here we have used exoglycosidase digestion and mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked oligosaccharides of human apo(a). 11294842 1 74 theme multikringle 160:171 arg1 Apolipoprotein 128:141 Apolipoprotein 128:141 Apolipoprotein(a) (apo(a)) 128:153 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 1 74 theme multikringle 160:171 arg1 glycoprotein 180:191 a multikringle domain glycoprotein 158:191 a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments 158:345 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 0 75 theme human 50:54 arg1 a 71:71 a 71:71 a 71:71 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 0 75 theme human 50:54 arg1 apolipoprotein 56:69 human apolipoprotein 50:69 human apolipoprotein(a) 50:72 Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. 11294842 8 76 gly monosialylated 1082:1095 arg1 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 NeuNAcalpha2-3Galbeta1-3GalNAc 1120:1149 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 8 76 gly monosialylated 1082:1095 arg1 structure 1109:1117 the monosialylated core type 1 structure 1078:1117 the monosialylated core type 1 structure 1078:1117 The O-glycans were mostly (80%) represented by the monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated and non-sialylated O-glycans also detected. 11294842 6 77 theme total 898:902 arg1 structures 920:929 the total oligosaccharide structures 894:929 the total oligosaccharide structures 894:929 Apo(a) contained two major N-glycans that accounted for 17% of the total oligosaccharide structures. 11294842 1 78 theme domain 173:178 arg1 Apolipoprotein 128:141 Apolipoprotein 128:141 Apolipoprotein(a) (apo(a)) 128:153 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 11294842 1 78 theme domain 173:178 arg1 glycoprotein 180:191 a multikringle domain glycoprotein 158:191 a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments 158:345 Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists covalently linked to apolipoprotein B100 of low density lipoprotein, to form the lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. 25456591 11 0 theme O-glycosylation 1884:1898 arg1 characterization 1850:1865 in-depth characterization 1841:1865 in-depth characterization of site-specific O-glycosylation of a simple mixture such as protein-based therapeutics 1841:1953 Thus, our approach is useful for in-depth characterization of site-specific O-glycosylation of a simple mixture such as protein-based therapeutics. 25456591 4 1 theme glycan-specific 974:988 arg1 fragments 990:998 glycan-specific fragments 974:998 glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR) 974:1080 Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). 25456591 6 2 theme ΔRt 1246:1248 arg1 filtering 1250:1258 ΔRt filtering 1246:1258 ΔRt filtering 1246:1258 This considerably reduced to 0% FDR by ΔRt filtering. 25456591 3 3 gly O-glycopeptides 738:752 arg2 O-glycopeptides 738:752 the corresponding intact O-glycopeptides 713:752 the corresponding intact O-glycopeptides 713:752 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 10 4 theme kappa-casein 1749:1760 arg1 T170 1741:1744 T170 1741:1744 T170 of kappa-casein 1741:1760 Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. 25456591 10 4 theme kappa-casein 1749:1760 arg1 T159 1719:1722 T159 1719:1722 T159 of Factor IX 1719:1735 Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. 25456591 3 5 theme glycan 815:820 arg1 database 822:829 an in-house glycan database 803:829 an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt) 803:909 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 1 6 theme improved 193:200 arg1 approach 216:223 an improved combinatorial approach 190:223 an improved combinatorial approach for identifying site-specific O-glycosylation using both glycan cleaved and non-cleaved methods 190:319 We reported an improved combinatorial approach for identifying site-specific O-glycosylation using both glycan cleaved and non-cleaved methods. 25456591 6 7 theme 0 1236:1236 arg1 % 1237:1237 % 1237:1237 % 1237:1237 This considerably reduced to 0% FDR by ΔRt filtering. 25456591 2 8 theme β-elimination 355:367 arg1 kit 369:371 a non-reducing β-elimination kit 340:371 a non-reducing β-elimination kit coupled with non-specific enzymes 340:405 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 5 9 gly glycopeptides 1177:1189 arg2 glycopeptides 1177:1189 multiple intact glycopeptides 1161:1189 multiple intact glycopeptides with a 31% FDR 1161:1204 Using fetuin as a model, all identified S/T elimination sites were matched to multiple intact glycopeptides with a 31% FDR. 25456591 11 10 theme mixture 1912:1918 arg1 O-glycosylation 1884:1898 site-specific O-glycosylation 1870:1898 site-specific O-glycosylation of a simple mixture such as protein-based therapeutics 1870:1953 Thus, our approach is useful for in-depth characterization of site-specific O-glycosylation of a simple mixture such as protein-based therapeutics. 25456591 0 11 theme retention 156:164 arg1 shift 171:175 retention time shift 156:175 retention time shift 156:175 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 5 12 theme multiple 1161:1168 arg1 glycopeptides 1177:1189 multiple intact glycopeptides 1161:1189 multiple intact glycopeptides with a 31% FDR 1161:1204 Using fetuin as a model, all identified S/T elimination sites were matched to multiple intact glycopeptides with a 31% FDR. 25456591 5 13 theme S/T 1123:1125 arg1 sites 1139:1143 all identified S/T elimination sites 1108:1143 all identified S/T elimination sites 1108:1143 Using fetuin as a model, all identified S/T elimination sites were matched to multiple intact glycopeptides with a 31% FDR. 25456591 3 14 theme corresponding 717:729 arg1 O-glycopeptides 738:752 the corresponding intact O-glycopeptides 713:752 the corresponding intact O-glycopeptides 713:752 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 2 15 theme cleaved 574:580 arg1 O-glycosylation 582:596 the cleaved O-glycosylation 570:596 the cleaved O-glycosylation 570:596 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 10 16 theme same 1701:1704 arg1 site 1706:1709 the same site 1697:1709 the same site 1697:1709 Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. 25456591 3 17 theme retention-time 884:897 arg1 ΔRt 906:908 ΔRt 906:908 ΔRt 906:908 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 3 17 theme retention-time 884:897 arg1 shift 899:903 the retention-time shift 880:903 the retention-time shift (ΔRt) 880:909 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 5 18 theme % 1200:1200 arg1 FDR 1202:1204 a 31% FDR 1196:1204 a 31% FDR 1196:1204 Using fetuin as a model, all identified S/T elimination sites were matched to multiple intact glycopeptides with a 31% FDR. 25456591 4 19 gly glycopeptide 917:928 arg2 glycopeptide 917:928 glycopeptide 917:928 glycopeptide 917:928 Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). 25456591 9 20 theme 3.3 1540:1542 arg1 % 1535:1535 % 1535:1535 % 1535:1535 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 9 21 theme same 1618:1621 arg1 sites 1637:1641 the same glycosylation sites 1614:1641 the same glycosylation sites 1614:1641 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 0 22 theme chromatography-tandem 86:106 arg1 spectrometry 113:124 liquid chromatography-tandem mass spectrometry 79:124 liquid chromatography-tandem mass spectrometry 79:124 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 4 23 theme False 1055:1059 arg1 FDR 1077:1079 FDR 1077:1079 FDR 1077:1079 Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). 25456591 4 23 theme False 1055:1059 arg1 Rate 1071:1074 False Discovery Rate 1055:1074 False Discovery Rate (FDR) 1055:1080 Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). 25456591 11 24 theme simple 1905:1910 arg1 mixture 1912:1918 a simple mixture 1903:1918 a simple mixture such as protein-based therapeutics 1903:1953 Thus, our approach is useful for in-depth characterization of site-specific O-glycosylation of a simple mixture such as protein-based therapeutics. 25456591 9 25 theme repeated 1579:1586 arg1 tags 1596:1599 repeated peptide tags 1579:1599 repeated peptide tags that covered the same glycosylation sites 1579:1641 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 8 26 theme glycosylation 1411:1423 arg1 sites 1425:1429 26 glycosylation sites 1408:1429 26 glycosylation sites each of which corresponds to 1-4 glycans 1408:1470 A total of 26 glycosylation sites each of which corresponds to 1-4 glycans were positively mapped and confirmed. 25456591 2 27 theme significant 495:505 arg1 reactions 512:520 significant side reactions 495:520 significant side reactions 495:520 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 0 28 theme protein 18:24 arg1 site 42:45 protein O-glycosylation site 18:45 protein O-glycosylation site 18:45 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 9 29 theme tags 1596:1599 arg1 exclusion 1566:1574 exclusion 1566:1574 exclusion 1566:1574 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 9 29 theme tags 1596:1599 arg1 filtering 1552:1560 ΔRt filtering 1548:1560 ΔRt filtering 1548:1560 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 2 30 theme database 550:557 arg1 search 559:564 an automatic database search 537:564 an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites 537:644 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 11 31 theme protein-based 1928:1940 arg1 therapeutics 1942:1953 protein-based therapeutics 1928:1953 protein-based therapeutics 1928:1953 Thus, our approach is useful for in-depth characterization of site-specific O-glycosylation of a simple mixture such as protein-based therapeutics. 25456591 0 32 theme site 42:45 arg1 Identification 0:13 Identification 0:13 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 0:176 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 4 33 theme glycopeptide 917:928 arg1 assignment 930:939 Each glycopeptide assignment 912:939 Each glycopeptide assignment 912:939 Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). 25456591 0 34 theme corresponding 51:63 arg1 glycans 65:71 corresponding glycans 51:71 corresponding glycans 51:71 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 5 35 theme identified 1112:1121 arg1 sites 1139:1143 all identified S/T elimination sites 1108:1143 all identified S/T elimination sites 1108:1143 Using fetuin as a model, all identified S/T elimination sites were matched to multiple intact glycopeptides with a 31% FDR. 25456591 3 36 theme ion 788:790 arg1 mass 792:795 accurate precursor ion mass 769:795 accurate precursor ion mass 769:795 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 11 37 theme site-specific 1870:1882 arg1 O-glycosylation 1884:1898 site-specific O-glycosylation 1870:1898 site-specific O-glycosylation of a simple mixture such as protein-based therapeutics 1870:1953 Thus, our approach is useful for in-depth characterization of site-specific O-glycosylation of a simple mixture such as protein-based therapeutics. 25456591 7 38 theme therapeutic 1325:1335 arg1 IX 1344:1345 therapeutic Factor IX 1325:1345 therapeutic Factor IX 1325:1345 This approach was then applied to a protein mixture composed of therapeutic Factor IX and Enbrel(®) mixed with fetuin and kappa-casein. 25456591 3 39 theme accurate 769:776 arg1 mass 792:795 accurate precursor ion mass 769:795 accurate precursor ion mass 769:795 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 1 40 theme glycan 282:287 arg1 methods 313:319 both glycan cleaved and non-cleaved methods 277:319 both glycan cleaved and non-cleaved methods 277:319 We reported an improved combinatorial approach for identifying site-specific O-glycosylation using both glycan cleaved and non-cleaved methods. 25456591 3 41 theme in-house 806:813 arg1 database 822:829 an in-house glycan database 803:829 an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt) 803:909 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 2 42 theme efficient 417:425 arg1 digestion 427:435 efficient digestion 417:435 efficient digestion 417:435 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 7 43 theme protein 1297:1303 arg1 mixture 1305:1311 a protein mixture 1295:1311 a protein mixture composed of therapeutic Factor IX and Enbrel(®) mixed with fetuin and kappa-casein 1295:1394 This approach was then applied to a protein mixture composed of therapeutic Factor IX and Enbrel(®) mixed with fetuin and kappa-casein. 25456591 9 44 gly glycosylation 1623:1635 arg2 sites 1637:1641 the same glycosylation sites 1614:1641 the same glycosylation sites 1614:1641 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 6 45 theme % 1237:1237 arg1 FDR 1239:1241 0% FDR 1236:1241 0% FDR 1236:1241 This considerably reduced to 0% FDR by ΔRt filtering. 25456591 1 46 theme combinatorial 202:214 arg1 approach 216:223 an improved combinatorial approach 190:223 an improved combinatorial approach for identifying site-specific O-glycosylation using both glycan cleaved and non-cleaved methods 190:319 We reported an improved combinatorial approach for identifying site-specific O-glycosylation using both glycan cleaved and non-cleaved methods. 25456591 3 47 theme mucin-type 859:868 arg1 core 871:874 GalNAc (mucin-type) core 851:874 GalNAc (mucin-type) core 851:874 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 0 48 gly O-glycosylation 26:40 arg2 site 42:45 protein O-glycosylation site 18:45 protein O-glycosylation site 18:45 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 2 49 theme non-reducing 342:353 arg1 kit 369:371 a non-reducing β-elimination kit 340:371 a non-reducing β-elimination kit coupled with non-specific enzymes 340:405 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 3 50 theme same 656:659 arg1 sample 661:666 the same sample 652:666 the same sample concurrently prepared without β-elimination 652:710 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 2 51 theme phosphorylation 624:638 arg1 sites 640:644 serine/threonine (S/T) phosphorylation sites 601:644 serine/threonine (S/T) phosphorylation sites 601:644 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 3 52 theme GalNAc 851:856 arg1 core 871:874 GalNAc (mucin-type) core 851:874 GalNAc (mucin-type) core 851:874 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 0 53 theme time 166:169 arg1 shift 171:175 retention time shift 156:175 retention time shift 156:175 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 1 54 theme site-specific 241:253 arg1 O-glycosylation 255:269 site-specific O-glycosylation 241:269 site-specific O-glycosylation using both glycan cleaved and non-cleaved methods 241:319 We reported an improved combinatorial approach for identifying site-specific O-glycosylation using both glycan cleaved and non-cleaved methods. 25456591 2 55 theme S/T 619:621 arg1 sites 640:644 serine/threonine (S/T) phosphorylation sites 601:644 serine/threonine (S/T) phosphorylation sites 601:644 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 11 56 gly O-glycosylation 1884:1898 arg1 mixture 1912:1918 a simple mixture 1903:1918 a simple mixture such as protein-based therapeutics 1903:1953 Thus, our approach is useful for in-depth characterization of site-specific O-glycosylation of a simple mixture such as protein-based therapeutics. 25456591 5 57 theme intact 1170:1175 arg1 glycopeptides 1177:1189 multiple intact glycopeptides 1161:1189 multiple intact glycopeptides with a 31% FDR 1161:1204 Using fetuin as a model, all identified S/T elimination sites were matched to multiple intact glycopeptides with a 31% FDR. 25456591 4 58 theme fragments 990:998 arg1 detection 961:969 the detection 957:969 the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR) 957:1080 Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). 25456591 1 59 dep methods 313:319 arg1 non-cleaved 301:311 non-cleaved 301:311 non-cleaved 301:311 We reported an improved combinatorial approach for identifying site-specific O-glycosylation using both glycan cleaved and non-cleaved methods. 25456591 1 59 dep methods 313:319 arg1 cleaved 289:295 cleaved 289:295 cleaved 289:295 We reported an improved combinatorial approach for identifying site-specific O-glycosylation using both glycan cleaved and non-cleaved methods. 25456591 5 60 theme elimination 1127:1137 arg1 sites 1139:1143 all identified S/T elimination sites 1108:1143 all identified S/T elimination sites 1108:1143 Using fetuin as a model, all identified S/T elimination sites were matched to multiple intact glycopeptides with a 31% FDR. 25456591 9 61 theme 33 1533:1534 arg1 % 1535:1535 % 1535:1535 % 1535:1535 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 4 62 theme collision-induced 1006:1022 arg1 CID 1038:1040 CID 1038:1040 CID 1038:1040 Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). 25456591 4 62 theme collision-induced 1006:1022 arg1 dissociation 1024:1035 collision-induced dissociation 1006:1035 collision-induced dissociation (CID) 1006:1041 Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). 25456591 5 63 with glycopeptides 1177:1189 arg1 FDR 1202:1204 a 31% FDR 1196:1204 a 31% FDR 1196:1204 Using fetuin as a model, all identified S/T elimination sites were matched to multiple intact glycopeptides with a 31% FDR. 25456591 0 64 theme liquid 79:84 arg1 spectrometry 113:124 liquid chromatography-tandem mass spectrometry 79:124 liquid chromatography-tandem mass spectrometry 79:124 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 2 65 theme non-specific 386:397 arg1 enzymes 399:405 non-specific enzymes 386:405 non-specific enzymes 386:405 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 0 66 theme mass 108:111 arg1 spectrometry 113:124 liquid chromatography-tandem mass spectrometry 79:124 liquid chromatography-tandem mass spectrometry 79:124 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 9 67 theme ΔRt 1548:1550 arg1 filtering 1552:1560 ΔRt filtering 1548:1560 ΔRt filtering 1548:1560 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 2 68 theme serine/threonine 601:616 arg1 sites 640:644 serine/threonine (S/T) phosphorylation sites 601:644 serine/threonine (S/T) phosphorylation sites 601:644 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 9 69 dep % 1535:1535 arg1 to 1537:1538 to 1537:1538 to 1537:1538 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 0 70 theme accurate 138:145 arg1 mass 147:150 accurate mass 138:150 accurate mass 138:150 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 4 71 theme Discovery 1061:1069 arg1 FDR 1077:1079 FDR 1077:1079 FDR 1077:1079 Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). 25456591 4 71 theme Discovery 1061:1069 arg1 Rate 1071:1074 False Discovery Rate 1055:1074 False Discovery Rate (FDR) 1055:1080 Each glycopeptide assignment was verified by the detection of glycan-specific fragments using collision-induced dissociation (CID) to estimate False Discovery Rate (FDR). 25456591 5 72 theme 31 1198:1199 arg1 % 1200:1200 % 1200:1200 % 1200:1200 Using fetuin as a model, all identified S/T elimination sites were matched to multiple intact glycopeptides with a 31% FDR. 25456591 2 73 theme O-glycan 438:445 arg1 cleavage 447:454 O-glycan cleavage 438:454 O-glycan cleavage 438:454 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 0 74 theme O-glycosylation 26:40 arg1 site 42:45 protein O-glycosylation site 18:45 protein O-glycosylation site 18:45 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 9 75 theme peptide 1588:1594 arg1 tags 1596:1599 repeated peptide tags 1579:1599 repeated peptide tags that covered the same glycosylation sites 1579:1641 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 2 76 theme side 507:510 arg1 reactions 512:520 significant side reactions 495:520 significant side reactions 495:520 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 2 77 theme automatic 540:548 arg1 search 559:564 an automatic database search 537:564 an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites 537:644 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 3 78 theme intact 731:736 arg1 O-glycopeptides 738:752 the corresponding intact O-glycopeptides 713:752 the corresponding intact O-glycopeptides 713:752 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 8 79 theme sites 1425:1429 arg1 total 1399:1403 A total 1397:1403 A total of 26 glycosylation sites each of which corresponds to 1-4 glycans 1397:1470 A total of 26 glycosylation sites each of which corresponds to 1-4 glycans were positively mapped and confirmed. 25456591 2 80 theme partial 461:467 arg1 dephosphorylation 469:485 partial dephosphorylation 461:485 partial dephosphorylation 461:485 In this approach, a non-reducing β-elimination kit coupled with non-specific enzymes performed efficient digestion, O-glycan cleavage, and partial dephosphorylation without significant side reactions, thus enabling an automatic database search for the cleaved O-glycosylation or serine/threonine (S/T) phosphorylation sites. 25456591 0 81 theme glycans 65:71 arg1 Identification 0:13 Identification 0:13 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 0:176 Identification of protein O-glycosylation site and corresponding glycans using liquid chromatography-tandem mass spectrometry via mapping accurate mass and retention time shift. 25456591 7 82 theme Factor 1337:1342 arg1 IX 1344:1345 therapeutic Factor IX 1325:1345 therapeutic Factor IX 1325:1345 This approach was then applied to a protein mixture composed of therapeutic Factor IX and Enbrel(®) mixed with fetuin and kappa-casein. 25456591 3 83 theme precursor 778:786 arg1 mass 792:795 accurate precursor ion mass 769:795 accurate precursor ion mass 769:795 From the same sample concurrently prepared without β-elimination, the corresponding intact O-glycopeptides were mapped by accurate precursor ion mass using an in-house glycan database majorly composed of GalNAc (mucin-type) core and the retention-time shift (ΔRt). 25456591 10 84 gly O-glycosylation 1678:1692 arg1 site 1706:1709 the same site 1697:1709 the same site 1697:1709 Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. 25456591 8 85 gly glycosylation 1411:1423 arg2 sites 1425:1429 26 glycosylation sites 1408:1429 26 glycosylation sites each of which corresponds to 1-4 glycans 1408:1470 A total of 26 glycosylation sites each of which corresponds to 1-4 glycans were positively mapped and confirmed. 25456591 8 85 gly glycosylation 1411:1423 arg2 26 1408:1409 26 1408:1409 26 1408:1409 A total of 26 glycosylation sites each of which corresponds to 1-4 glycans were positively mapped and confirmed. 25456591 9 86 theme glycosylation 1623:1635 arg1 sites 1637:1641 the same glycosylation sites 1614:1641 the same glycosylation sites 1614:1641 The FDR decreased from 33% to 3.3% by ΔRt filtering and exclusion of repeated peptide tags that covered the same glycosylation sites. 25456591 10 87 from phosphorylation 1658:1672 arg1 site 1706:1709 the same site 1697:1709 the same site 1697:1709 Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. 25456591 11 88 theme in-depth 1841:1848 arg1 characterization 1850:1865 in-depth characterization 1841:1865 in-depth characterization of site-specific O-glycosylation of a simple mixture such as protein-based therapeutics 1841:1953 Thus, our approach is useful for in-depth characterization of site-specific O-glycosylation of a simple mixture such as protein-based therapeutics. 25456591 10 89 from O-glycosylation 1678:1692 arg1 site 1706:1709 the same site 1697:1709 the same site 1697:1709 Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. 25456591 10 90 theme Factor 1727:1732 arg1 IX 1734:1735 Factor IX 1727:1735 Factor IX 1727:1735 Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. 25456591 10 91 dep phosphorylation 1658:1672 arg1 the 1654:1656 the 1654:1656 the 1654:1656 Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. 25456591 10 92 theme IX 1734:1735 arg1 T170 1741:1744 T170 1741:1744 T170 of kappa-casein 1741:1760 Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. 25456591 10 92 theme IX 1734:1735 arg1 T159 1719:1722 T159 1719:1722 T159 of Factor IX 1719:1735 Moreover, the phosphorylation and O-glycosylation on the same site such as T159 of Factor IX and T170 of kappa-casein were able to be unambiguously differentiated. 9492296 0 0 theme phosphatase 74:84 arg1 CD45 86:89 human leukocyte tyrosine phosphatase CD45 49:89 human leukocyte tyrosine phosphatase CD45 49:89 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45. 9492296 4 1 theme cell 859:862 arg1 residues 884:891 cell surface sialic acid residues 859:891 cell surface sialic acid residues 859:891 CD45 consists of several isoforms which were isolated after cell surface sialic acid residues were labeled by periodate/NaB3H4 treatment. 9492296 1 2 theme cell 141:144 arg1 CD45 167:170 the human leukocyte cell surface glycoprotein CD45 121:170 the human leukocyte cell surface glycoprotein CD45 121:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 3 3 mod modified 726:733 arg1 % 711:711 15% 709:711 15% 709:711 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 3 3 mod modified 726:733 arg1 which 716:720 which 716:720 which 716:720 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 3 3 mod modified 726:733 arg3 chains 767:772 poly (N-acetyllactosamine) chains 740:772 poly (N-acetyllactosamine) chains in different extensions 740:796 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 0 4 theme tyrosine 65:72 arg1 CD45 86:89 human leukocyte tyrosine phosphatase CD45 49:89 human leukocyte tyrosine phosphatase CD45 49:89 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45. 9492296 1 5 gly glycoprotein 154:165 arg1 glycoprotein 154:165 the human leukocyte cell surface glycoprotein CD45 121:170 the human leukocyte cell surface glycoprotein CD45 121:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 1 6 theme surface 146:152 arg1 CD45 167:170 the human leukocyte cell surface glycoprotein CD45 121:170 the human leukocyte cell surface glycoprotein CD45 121:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 1 7 theme NaB3H4 261:266 arg1 presence 249:256 the presence 245:256 the presence of NaB3H4 245:266 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 5 8 theme Bio-Gel 937:943 arg1 chromatography 956:969 Bio-Gel P-6 column chromatography 937:969 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment 937:1113 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 4 9 theme sialic 872:877 arg1 residues 884:891 cell surface sialic acid residues 859:891 cell surface sialic acid residues 859:891 CD45 consists of several isoforms which were isolated after cell surface sialic acid residues were labeled by periodate/NaB3H4 treatment. 9492296 4 10 theme several 816:822 arg1 isoforms 824:831 several isoforms 816:831 several isoforms which were isolated after cell surface sialic acid residues were labeled by periodate/NaB3H4 treatment 816:934 CD45 consists of several isoforms which were isolated after cell surface sialic acid residues were labeled by periodate/NaB3H4 treatment. 9492296 2 11 dep acidic 344:349 arg1 % 354:354 36% 352:354 36% 352:354 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 3 12 theme Bio-Gel 536:542 arg1 column 548:553 a Bio-Gel P-4 column 534:553 a Bio-Gel P-4 column 534:553 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 0 13 theme CD45 86:89 arg1 chains 39:44 the O-linked sugar chains 20:44 the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45 20:89 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45. 9492296 2 14 dep Arthrobacter 429:440 arg1 ureafaciens 442:452 ureafaciens 442:452 ureafaciens 442:452 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 2 15 theme acidic 344:349 arg1 oligosaccharides 357:372 neutral (64%) and acidic (36%) oligosaccharides 326:372 neutral (64%) and acidic (36%) oligosaccharides 326:372 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 3 16 theme which 716:720 arg1 % 711:711 15% 709:711 15% 709:711 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 3 16 theme which 716:720 arg1 which 716:720 which 716:720 which 716:720 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 2 17 theme column 276:281 arg1 chromatography 283:296 Mono Q column chromatography 269:296 Mono Q column chromatography 269:296 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 1 18 theme glycoprotein 154:165 arg1 CD45 167:170 the human leukocyte cell surface glycoprotein CD45 121:170 the human leukocyte cell surface glycoprotein CD45 121:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 3 19 from chains 767:772 arg1 extensions 787:796 different extensions 777:796 different extensions 777:796 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 2 20 theme Q 274:274 arg1 chromatography 283:296 Mono Q column chromatography 269:296 Mono Q column chromatography 269:296 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 1 21 theme CD45 167:170 arg1 oligosaccharides 205:220 tritium-labeled oligosaccharides 189:220 tritium-labeled oligosaccharides 189:220 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 1 21 theme CD45 167:170 arg1 chains 111:116 The O-linked sugar chains 92:116 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 92:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 2 22 theme neutral 413:419 arg1 ones 421:424 neutral ones 413:424 neutral ones 413:424 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 2 23 theme sialidase 454:462 arg1 treatment 464:472 Arthrobacter ureafaciens sialidase treatment 429:472 Arthrobacter ureafaciens sialidase treatment 429:472 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 5 24 theme glycopeptide/oligosaccharides 1007:1035 arg1 mixture 976:982 a mixture 974:982 a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment 974:1113 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 2 25 theme neutral 326:332 arg1 oligosaccharides 357:372 neutral (64%) and acidic (36%) oligosaccharides 326:372 neutral (64%) and acidic (36%) oligosaccharides 326:372 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 5 26 theme sialylated 1147:1156 arg1 oligosaccharides 1165:1180 the sialylated core 2 oligosaccharides 1143:1180 the sialylated core 2 oligosaccharides 1143:1180 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 0 27 theme Structural 0:9 arg1 study 11:15 Structural study 0:15 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45 0:89 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45. 9492296 3 28 theme sequential 558:567 arg1 digestion 584:592 sequential exoglycosidase digestion 558:592 sequential exoglycosidase digestion 558:592 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 5 29 gly sialylated 1147:1156 arg1 oligosaccharides 1165:1180 the sialylated core 2 oligosaccharides 1143:1180 the sialylated core 2 oligosaccharides 1143:1180 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 3 30 theme poly 740:743 arg1 chains 767:772 poly (N-acetyllactosamine) chains 740:772 poly (N-acetyllactosamine) chains in different extensions 740:796 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 4 31 theme periodate/NaB3H4 909:924 arg1 treatment 926:934 periodate/NaB3H4 treatment 909:934 periodate/NaB3H4 treatment 909:934 CD45 consists of several isoforms which were isolated after cell surface sialic acid residues were labeled by periodate/NaB3H4 treatment. 9492296 0 32 link O-linked 24:31 arg1 chains 39:44 the O-linked sugar chains 20:44 the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45 20:89 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45. 9492296 3 33 theme P-4 544:546 arg1 column 548:553 a Bio-Gel P-4 column 534:553 a Bio-Gel P-4 column 534:553 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 5 34 theme P-6 945:947 arg1 chromatography 956:969 Bio-Gel P-6 column chromatography 937:969 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment 937:1113 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 5 35 theme mixture 976:982 arg1 chromatography 956:969 Bio-Gel P-6 column chromatography 937:969 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment 937:1113 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 1 36 theme O-linked 96:103 arg1 oligosaccharides 205:220 tritium-labeled oligosaccharides 189:220 tritium-labeled oligosaccharides 189:220 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 1 36 theme O-linked 96:103 arg1 chains 111:116 The O-linked sugar chains 92:116 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 92:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 1 37 theme tritium-labeled 189:203 arg1 oligosaccharides 205:220 tritium-labeled oligosaccharides 189:220 tritium-labeled oligosaccharides 189:220 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 1 37 theme tritium-labeled 189:203 arg1 chains 111:116 The O-linked sugar chains 92:116 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 92:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 0 38 theme sugar 33:37 arg1 chains 39:44 the O-linked sugar chains 20:44 the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45 20:89 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45. 9492296 5 39 theme mild 1079:1082 arg1 treatment 1105:1113 mild alkaline borohydride treatment 1079:1113 mild alkaline borohydride treatment 1079:1113 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 3 40 contain contains 657:664 arg1 CD45 652:655 human leukocyte CD45 636:655 human leukocyte CD45 636:655 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 3 40 contain contains 657:664 arg2 core 684:687 core 2 684:689 core 2 684:689 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 3 40 contain contains 657:664 arg2 core 673:676 core 1 673:678 core 1 673:678 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 0 41 theme O-linked 24:31 arg1 chains 39:44 the O-linked sugar chains 20:44 the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45 20:89 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45. 9492296 5 42 theme CD45 1201:1204 arg1 isoforms 1206:1213 CD45 isoforms 1201:1213 CD45 isoforms 1201:1213 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 2 43 theme Arthrobacter 429:440 arg1 treatment 464:472 Arthrobacter ureafaciens sialidase treatment 429:472 Arthrobacter ureafaciens sialidase treatment 429:472 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 3 44 theme human 636:640 arg1 CD45 652:655 human leukocyte CD45 636:655 human leukocyte CD45 636:655 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 0 45 theme human 49:53 arg1 CD45 86:89 human leukocyte tyrosine phosphatase CD45 49:89 human leukocyte tyrosine phosphatase CD45 49:89 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45. 9492296 3 46 theme exoglycosidase 569:582 arg1 digestion 584:592 sequential exoglycosidase digestion 558:592 sequential exoglycosidase digestion 558:592 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 5 47 theme core 1158:1161 arg1 oligosaccharides 1165:1180 the sialylated core 2 oligosaccharides 1143:1180 the sialylated core 2 oligosaccharides 1143:1180 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 1 48 theme sugar 105:109 arg1 oligosaccharides 205:220 tritium-labeled oligosaccharides 189:220 tritium-labeled oligosaccharides 189:220 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 1 48 theme sugar 105:109 arg1 chains 111:116 The O-linked sugar chains 92:116 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 92:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 0 49 theme chains 39:44 arg1 study 11:15 Structural study 0:15 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45 0:89 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45. 9492296 4 50 theme acid 879:882 arg1 residues 884:891 cell surface sialic acid residues 859:891 cell surface sialic acid residues 859:891 CD45 consists of several isoforms which were isolated after cell surface sialic acid residues were labeled by periodate/NaB3H4 treatment. 9492296 3 51 theme leukocyte 642:650 arg1 CD45 652:655 human leukocyte CD45 636:655 human leukocyte CD45 636:655 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 3 52 theme Structural 475:484 arg1 studies 486:492 Structural studies 475:492 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis 475:620 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 3 53 theme N-acetyllactosamine 746:764 arg1 chains 767:772 poly (N-acetyllactosamine) chains 740:772 poly (N-acetyllactosamine) chains in different extensions 740:796 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 1 54 from beta-elimination 225:240 arg1 presence 249:256 the presence 245:256 the presence of NaB3H4 245:266 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 5 55 theme alkaline 1084:1091 arg1 treatment 1105:1113 mild alkaline borohydride treatment 1079:1113 mild alkaline borohydride treatment 1079:1113 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 2 56 theme Mono 269:272 arg1 chromatography 283:296 Mono Q column chromatography 269:296 Mono Q column chromatography 269:296 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 2 57 dep neutral 326:332 arg1 % 337:337 64% 335:337 64% 335:337 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 5 58 theme column 949:954 arg1 chromatography 956:969 Bio-Gel P-6 column chromatography 937:969 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment 937:1113 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 3 59 dep core 673:676 arg1 oligosaccharides 691:706 oligosaccharides 691:706 oligosaccharides 691:706 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 5 60 theme tritium-labeled 991:1005 arg1 glycopeptide/oligosaccharides 1007:1035 the tritium-labeled glycopeptide/oligosaccharides 987:1035 the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment 987:1113 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 3 61 theme oligosaccharide 502:516 arg1 studies 486:492 Structural studies 475:492 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis 475:620 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 4 62 theme surface 864:870 arg1 residues 884:891 cell surface sialic acid residues 859:891 cell surface sialic acid residues 859:891 CD45 consists of several isoforms which were isolated after cell surface sialic acid residues were labeled by periodate/NaB3H4 treatment. 9492296 5 63 theme borohydride 1093:1103 arg1 treatment 1105:1113 mild alkaline borohydride treatment 1079:1113 mild alkaline borohydride treatment 1079:1113 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 0 64 theme leukocyte 55:63 arg1 CD45 86:89 human leukocyte tyrosine phosphatase CD45 49:89 human leukocyte tyrosine phosphatase CD45 49:89 Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45. 9492296 3 65 theme methylation 601:611 arg1 analysis 613:620 methylation analysis 601:620 methylation analysis 601:620 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 1 66 theme human 125:129 arg1 CD45 167:170 the human leukocyte cell surface glycoprotein CD45 121:170 the human leukocyte cell surface glycoprotein CD45 121:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 2 67 theme oligosaccharides 357:372 arg1 latter 379:384 latter 379:384 latter 379:384 Mono Q column chromatography revealed that they comprise neutral (64%) and acidic (36%) oligosaccharides, the latter of which were converted to neutral ones by Arthrobacter ureafaciens sialidase treatment. 9492296 1 68 link O-linked 96:103 arg1 oligosaccharides 205:220 tritium-labeled oligosaccharides 189:220 tritium-labeled oligosaccharides 189:220 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 1 68 link O-linked 96:103 arg1 chains 111:116 The O-linked sugar chains 92:116 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 92:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 5 69 theme oligosaccharides 1165:1180 arg1 distribution 1127:1138 distribution 1127:1138 distribution of the sialylated core 2 oligosaccharides 1127:1180 Bio-Gel P-6 column chromatography of a mixture of the tritium-labeled glycopeptide/oligosaccharides obtained by pronase-digestion followed by mild alkaline borohydride treatment showed that distribution of the sialylated core 2 oligosaccharides is different among CD45 isoforms. 9492296 3 70 dep contains 657:664 arg1 modified 726:733 modified 726:733 are modified with poly (N-acetyllactosamine) chains in different extensions 722:796 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 9492296 1 71 theme leukocyte 131:139 arg1 CD45 167:170 the human leukocyte cell surface glycoprotein CD45 121:170 the human leukocyte cell surface glycoprotein CD45 121:170 The O-linked sugar chains of the human leukocyte cell surface glycoprotein CD45 were released as tritium-labeled oligosaccharides by beta-elimination in the presence of NaB3H4. 9492296 3 72 theme different 777:785 arg1 extensions 787:796 different extensions 777:796 different extensions 777:796 Structural studies of each oligosaccharide fractionated on a Bio-Gel P-4 column by sequential exoglycosidase digestion and by methylation analysis revealed that human leukocyte CD45 contains mainly core 1 and core 2 oligosaccharides, 15% of which are modified with poly (N-acetyllactosamine) chains in different extensions. 2737211 0 0 theme analysis 201:208 arg1 combination 171:181 a combination 169:181 a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy 169:240 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 5 1 theme structures 1105:1114 arg1 structures 1105:1114 the described oligosaccharide structures 1075:1114 the described oligosaccharide structures 1075:1114 Sixteen of the described oligosaccharide structures are original. 2737211 5 1 theme structures 1105:1114 arg1 Sixteen 1064:1070 Sixteen 1064:1070 Sixteen 1064:1070 Sixteen of the described oligosaccharide structures are original. 2737211 2 2 theme spectrometry 598:609 arg1 combination 550:560 a combination 548:560 a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy 548:641 Their primary structures were completely resolved by applying a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy. 2737211 3 3 dep beta 797:800 arg1 [GlcNAc 806:812 [GlcNAc 806:812 [GlcNAc(beta 1-6) 806:822 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 3 3 dep beta 797:800 arg1 1-6 819:821 beta 1-6 814:821 beta 1-6 814:821 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 0 4 theme permethylation 186:199 arg1 analysis 201:208 permethylation analysis 186:208 permethylation analysis 186:208 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 4 5 theme core 858:861 arg1 elongation 839:848 The elongation 835:848 The elongation of this core 835:861 The elongation of this core arises by chain lengthening only on the GlcNAc(beta 1-6) branch for the sialylated compounds, leading to a dodecasaccharide, and on both branches for the neutral compounds leading to a nonasaccharide. 2737211 0 6 theme human 109:113 arg1 region 148:153 the human secretory immunoglobulin A hinge region 105:153 the human secretory immunoglobulin A hinge region 105:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 3 7 theme oligosaccharide 680:694 arg1 alditols 696:703 twenty three oligosaccharide alditols 667:703 twenty three oligosaccharide alditols 667:703 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 0 8 theme 400-MHz 214:220 arg1 spectroscopy 229:240 400-MHz 1H-NMR spectroscopy 214:240 400-MHz 1H-NMR spectroscopy 214:240 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 2 9 theme analysis 571:578 arg1 combination 550:560 a combination 548:560 a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy 548:641 Their primary structures were completely resolved by applying a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy. 2737211 6 10 theme X 1214:1214 arg1 determinants 1228:1239 X blood group determinants 1214:1239 X blood group determinants 1214:1239 Moreover, some of the fucosylated structures were found to support Le(a), Le(b) and X blood group determinants. 2737211 1 11 theme human 317:321 arg1 region 361:366 the human milk secretory immunoglobulin A hinge region 313:366 the human milk secretory immunoglobulin A hinge region 313:366 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 0 12 theme immunoglobulin 125:138 arg1 region 148:153 the human secretory immunoglobulin A hinge region 105:153 the human secretory immunoglobulin A hinge region 105:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 5 13 theme described 1079:1087 arg1 structures 1105:1114 the described oligosaccharide structures 1075:1114 the described oligosaccharide structures 1075:1114 Sixteen of the described oligosaccharide structures are original. 2737211 0 14 theme spectroscopy 229:240 arg1 combination 171:181 a combination 169:181 a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy 169:240 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 3 15 contain possess 727:733 arg2 core 746:749 a type two core 735:749 a type two core consisting of the branched trisaccharide 735:790 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 3 15 contain possess 727:733 arg1 all 723:725 all 723:725 all 723:725 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 0 16 theme secretory 115:123 arg1 region 148:153 the human secretory immunoglobulin A hinge region 105:153 the human secretory immunoglobulin A hinge region 105:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 5 17 theme oligosaccharide 1089:1103 arg1 structures 1105:1114 the described oligosaccharide structures 1075:1114 the described oligosaccharide structures 1075:1114 Sixteen of the described oligosaccharide structures are original. 2737211 0 18 theme 1H-NMR 222:227 arg1 spectroscopy 229:240 400-MHz 1H-NMR spectroscopy 214:240 400-MHz 1H-NMR spectroscopy 214:240 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 6 19 gly fucosylated 1152:1162 arg1 structures 1164:1173 the fucosylated structures 1148:1173 the fucosylated structures 1148:1173 Moreover, some of the fucosylated structures were found to support Le(a), Le(b) and X blood group determinants. 2737211 6 20 theme fucosylated 1152:1162 arg1 structures 1164:1173 the fucosylated structures 1148:1173 the fucosylated structures 1148:1173 Moreover, some of the fucosylated structures were found to support Le(a), Le(b) and X blood group determinants. 2737211 2 21 theme sugar 565:569 arg1 analysis 571:578 sugar analysis 565:578 sugar analysis 565:578 Their primary structures were completely resolved by applying a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy. 2737211 2 22 theme primary 492:498 arg1 structures 500:509 Their primary structures 486:509 Their primary structures 486:509 Their primary structures were completely resolved by applying a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy. 2737211 3 23 theme branched 769:776 arg1 trisaccharide 778:790 the branched trisaccharide 765:790 the branched trisaccharide 765:790 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 4 24 theme sialylated 935:944 arg1 compounds 946:954 the sialylated compounds 931:954 the sialylated compounds 931:954 The elongation of this core arises by chain lengthening only on the GlcNAc(beta 1-6) branch for the sialylated compounds, leading to a dodecasaccharide, and on both branches for the neutral compounds leading to a nonasaccharide. 2737211 0 25 theme Primary 0:6 arg1 structure 8:16 Primary structure 0:16 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region 0:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 1 26 theme milk 323:326 arg1 region 361:366 the human milk secretory immunoglobulin A hinge region 313:366 the human milk secretory immunoglobulin A hinge region 313:366 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 4 27 gly sialylated 935:944 arg1 compounds 946:954 the sialylated compounds 931:954 the sialylated compounds 931:954 The elongation of this core arises by chain lengthening only on the GlcNAc(beta 1-6) branch for the sialylated compounds, leading to a dodecasaccharide, and on both branches for the neutral compounds leading to a nonasaccharide. 2737211 4 28 theme chain 873:877 arg1 lengthening 879:889 chain lengthening 873:889 chain lengthening 873:889 The elongation of this core arises by chain lengthening only on the GlcNAc(beta 1-6) branch for the sialylated compounds, leading to a dodecasaccharide, and on both branches for the neutral compounds leading to a nonasaccharide. 2737211 4 29 theme neutral 1017:1023 arg1 compounds 1025:1033 the neutral compounds 1013:1033 the neutral compounds leading to a nonasaccharide 1013:1061 The elongation of this core arises by chain lengthening only on the GlcNAc(beta 1-6) branch for the sialylated compounds, leading to a dodecasaccharide, and on both branches for the neutral compounds leading to a nonasaccharide. 2737211 1 30 theme secretory 328:336 arg1 region 361:366 the human milk secretory immunoglobulin A hinge region 313:366 the human milk secretory immunoglobulin A hinge region 313:366 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 0 31 theme hinge 142:146 arg1 region 148:153 the human secretory immunoglobulin A hinge region 105:153 the human secretory immunoglobulin A hinge region 105:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 6 32 theme group 1222:1226 arg1 determinants 1228:1239 X blood group determinants 1214:1239 X blood group determinants 1214:1239 Moreover, some of the fucosylated structures were found to support Le(a), Le(b) and X blood group determinants. 2737211 1 33 theme immunoglobulin 338:351 arg1 region 361:366 the human milk secretory immunoglobulin A hinge region 313:366 the human milk secretory immunoglobulin A hinge region 313:366 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 0 34 theme A 140:140 arg1 region 148:153 the human secretory immunoglobulin A hinge region 105:153 the human secretory immunoglobulin A hinge region 105:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 0 35 theme neutral 34:40 arg1 oligosaccharides 61:76 twenty three neutral and monosialylated oligosaccharides 21:76 twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region 21:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 1 36 theme A 353:353 arg1 region 361:366 the human milk secretory immunoglobulin A hinge region 313:366 the human milk secretory immunoglobulin A hinge region 313:366 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 2 37 theme mass 593:596 arg1 spectrometry 598:609 methylation mass spectrometry 581:609 methylation mass spectrometry 581:609 Their primary structures were completely resolved by applying a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy. 2737211 1 38 theme amino-bonded 420:431 arg1 column 440:445 an amino-bonded silica column 417:445 an amino-bonded silica column 417:445 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 3 39 theme present 651:657 arg1 report 659:664 the present report 647:664 the present report 647:664 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 1 40 theme hinge 355:359 arg1 region 361:366 the human milk secretory immunoglobulin A hinge region 313:366 the human milk secretory immunoglobulin A hinge region 313:366 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 2 41 theme methylation 581:591 arg1 spectrometry 598:609 methylation mass spectrometry 581:609 methylation mass spectrometry 581:609 Their primary structures were completely resolved by applying a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy. 2737211 1 42 theme silica 433:438 arg1 column 440:445 an amino-bonded silica column 417:445 an amino-bonded silica column 417:445 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 1 43 theme Sialooligosaccharide 243:262 arg1 alditols 290:297 Sialooligosaccharide and asialooligosaccharide alditols 243:297 Sialooligosaccharide and asialooligosaccharide alditols 243:297 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 0 44 theme monosialylated 46:59 arg1 oligosaccharides 61:76 twenty three neutral and monosialylated oligosaccharides 21:76 twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region 21:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 3 45 theme beta 814:817 arg1 [GlcNAc 806:812 [GlcNAc 806:812 [GlcNAc(beta 1-6) 806:822 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 3 45 theme beta 814:817 arg1 1-6 819:821 beta 1-6 814:821 beta 1-6 814:821 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 4 46 theme GlcNAc 903:908 arg1 branch 920:925 the GlcNAc(beta 1-6) branch 899:925 the GlcNAc(beta 1-6) branch 899:925 The elongation of this core arises by chain lengthening only on the GlcNAc(beta 1-6) branch for the sialylated compounds, leading to a dodecasaccharide, and on both branches for the neutral compounds leading to a nonasaccharide. 2737211 4 46 theme GlcNAc 903:908 arg1 1-6 915:917 beta 1-6 910:917 beta 1-6 910:917 The elongation of this core arises by chain lengthening only on the GlcNAc(beta 1-6) branch for the sialylated compounds, leading to a dodecasaccharide, and on both branches for the neutral compounds leading to a nonasaccharide. 2737211 4 47 theme beta 910:913 arg1 branch 920:925 the GlcNAc(beta 1-6) branch 899:925 the GlcNAc(beta 1-6) branch 899:925 The elongation of this core arises by chain lengthening only on the GlcNAc(beta 1-6) branch for the sialylated compounds, leading to a dodecasaccharide, and on both branches for the neutral compounds leading to a nonasaccharide. 2737211 4 47 theme beta 910:913 arg1 1-6 915:917 beta 1-6 910:917 beta 1-6 910:917 The elongation of this core arises by chain lengthening only on the GlcNAc(beta 1-6) branch for the sialylated compounds, leading to a dodecasaccharide, and on both branches for the neutral compounds leading to a nonasaccharide. 2737211 2 48 theme spectroscopy 630:641 arg1 combination 550:560 a combination 548:560 a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy 548:641 Their primary structures were completely resolved by applying a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy. 2737211 0 49 attach linked 95:100 arg1 region 148:153 the human secretory immunoglobulin A hinge region 105:153 the human secretory immunoglobulin A hinge region 105:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 0 49 attach linked 95:100 arg2 oligosaccharides 61:76 twenty three neutral and monosialylated oligosaccharides 21:76 twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region 21:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 6 50 theme blood 1216:1220 arg1 determinants 1228:1239 X blood group determinants 1214:1239 X blood group determinants 1214:1239 Moreover, some of the fucosylated structures were found to support Le(a), Le(b) and X blood group determinants. 2737211 2 51 theme 1H-NMR 623:628 arg1 spectroscopy 630:641 400-MHz 1H-NMR spectroscopy 615:641 400-MHz 1H-NMR spectroscopy 615:641 Their primary structures were completely resolved by applying a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy. 2737211 3 52 theme type 737:740 arg1 core 746:749 a type two core 735:749 a type two core consisting of the branched trisaccharide 735:790 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 2 53 theme 400-MHz 615:621 arg1 spectroscopy 630:641 400-MHz 1H-NMR spectroscopy 615:641 400-MHz 1H-NMR spectroscopy 615:641 Their primary structures were completely resolved by applying a combination of sugar analysis, methylation mass spectrometry and 400-MHz 1H-NMR spectroscopy. 2737211 1 54 theme octadecyl-bonded 454:469 arg1 column 478:483 an octadecyl-bonded silica column 451:483 an octadecyl-bonded silica column 451:483 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 1 55 attach derived 300:306 arg1 region 361:366 the human milk secretory immunoglobulin A hinge region 313:366 the human milk secretory immunoglobulin A hinge region 313:366 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 1 55 attach derived 300:306 arg2 alditols 290:297 Sialooligosaccharide and asialooligosaccharide alditols 243:297 Sialooligosaccharide and asialooligosaccharide alditols 243:297 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 1 56 theme asialooligosaccharide 268:288 arg1 alditols 290:297 Sialooligosaccharide and asialooligosaccharide alditols 243:297 Sialooligosaccharide and asialooligosaccharide alditols 243:297 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 1 57 theme silica 471:476 arg1 column 478:483 an octadecyl-bonded silica column 451:483 an octadecyl-bonded silica column 451:483 Sialooligosaccharide and asialooligosaccharide alditols, derived from the human milk secretory immunoglobulin A hinge region, have been purified by HPLC using, successively, an amino-bonded silica column and an octadecyl-bonded silica column. 2737211 3 58 dep described 709:717 arg1 beta 797:800 beta 1-3 797:804 beta 1-3 797:804 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 3 58 dep described 709:717 arg1 Gal 793:795 Gal 793:795 Gal 793:795 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 3 58 dep described 709:717 arg1 GalNAc-ol 824:832 GalNAc-ol 824:832 GalNAc-ol 824:832 In the present report, twenty three oligosaccharide alditols are described and all possess a type two core consisting of the branched trisaccharide: Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc-ol. 2737211 0 59 theme oligosaccharides 61:76 arg1 structure 8:16 Primary structure 0:16 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region 0:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 2737211 0 60 gly monosialylated 46:59 arg1 oligosaccharides 61:76 twenty three neutral and monosialylated oligosaccharides 21:76 twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region 21:153 Primary structure of twenty three neutral and monosialylated oligosaccharides O-glycosidically linked to the human secretory immunoglobulin A hinge region determined by a combination of permethylation analysis and 400-MHz 1H-NMR spectroscopy. 6966283 3 0 theme protein 232:238 arg1 protein 232:238 the protein 228:238 the protein 228:238 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 3 0 theme protein 232:238 arg1 residues 216:223 3 separate asparaginyl residues 193:223 3 separate asparaginyl residues of the protein 193:238 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 4 1 theme oligosaccharide 328:342 arg1 chains 344:349 the A-type oligosaccharide chains 317:349 the A-type oligosaccharide chains which consist of Man3, Gal2 317:377 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 4 1 theme oligosaccharide 328:342 arg1 NeuAc 395:399 (NeuAc)2 394:401 (NeuAc)2 394:401 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 4 1 theme oligosaccharide 328:342 arg1 GlcNAc 381:386 (GlcNAc)4 380:388 (GlcNAc)4 380:388 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 10 2 theme chains 1044:1049 arg1 position 1025:1032 the (a) and/or (b) position 1006:1032 position 1025:1032 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 5 3 attach attaches 447:454 arg2 One 404:406 One 404:406 One 404:406 One of the three asparaginyl residues also attaches to a B-type oligosaccharide chain, which consists of Man3, Gal3, (GlcNAc)5, and (NeuAc)3. 6966283 5 3 attach attaches 447:454 arg1 chain 484:488 a B-type oligosaccharide chain 459:488 a B-type oligosaccharide chain 459:488 One of the three asparaginyl residues also attaches to a B-type oligosaccharide chain, which consists of Man3, Gal3, (GlcNAc)5, and (NeuAc)3. 6966283 5 3 attach attaches 447:454 arg2 residues 433:440 the three asparaginyl residues 411:440 the three asparaginyl residues 411:440 One of the three asparaginyl residues also attaches to a B-type oligosaccharide chain, which consists of Man3, Gal3, (GlcNAc)5, and (NeuAc)3. 6966283 10 4 theme Gal 954:956 arg1 beta 960:963 3 Gal 1 beta 952:963 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage 952:1080 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 10 5 theme A-type 1037:1042 arg1 chains 1044:1049 A-type chains 1037:1049 A-type chains 1037:1049 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 0 6 from Studies 0:6 arg1 chains 31:36 the oligosaccharide chains 11:36 the oligosaccharide chains of human alpha 11:51 Studies on the oligosaccharide chains of human alpha 1-protease inhibitor. 6966283 5 7 theme oligosaccharide 468:482 arg1 chain 484:488 a B-type oligosaccharide chain 459:488 a B-type oligosaccharide chain 459:488 One of the three asparaginyl residues also attaches to a B-type oligosaccharide chain, which consists of Man3, Gal3, (GlcNAc)5, and (NeuAc)3. 6966283 3 8 theme side 169:172 arg1 chains 174:179 three oligosaccharide side chains 147:179 three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages 147:261 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 5 9 theme residues 433:440 arg1 residues 433:440 the three asparaginyl residues 411:440 the three asparaginyl residues 411:440 One of the three asparaginyl residues also attaches to a B-type oligosaccharide chain, which consists of Man3, Gal3, (GlcNAc)5, and (NeuAc)3. 6966283 5 9 theme residues 433:440 arg1 One 404:406 One 404:406 One 404:406 One of the three asparaginyl residues also attaches to a B-type oligosaccharide chain, which consists of Man3, Gal3, (GlcNAc)5, and (NeuAc)3. 6966283 11 10 theme alpha 1108:1112 arg1 inhibitor 1125:1133 human alpha 1-protease inhibitor 1102:1133 human alpha 1-protease inhibitor 1102:1133 The sialic acid of human alpha 1-protease inhibitor was determined to be N-acetylneuraminic acid. 6966283 11 11 theme inhibitor 1125:1133 arg1 acid 1094:1097 The sialic acid 1083:1097 The sialic acid of human alpha 1-protease inhibitor 1083:1133 The sialic acid of human alpha 1-protease inhibitor was determined to be N-acetylneuraminic acid. 6966283 11 11 theme inhibitor 1125:1133 arg1 acid 1175:1178 N-acetylneuraminic acid 1156:1178 N-acetylneuraminic acid 1156:1178 The sialic acid of human alpha 1-protease inhibitor was determined to be N-acetylneuraminic acid. 6966283 4 12 theme residues 293:300 arg1 residues 293:300 the three asparaginyl residues 271:300 the three asparaginyl residues 271:300 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 4 12 theme residues 293:300 arg1 Two 264:266 Two 264:266 Two 264:266 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 11 13 theme N-acetylneuraminic 1156:1173 arg1 acid 1094:1097 The sialic acid 1083:1097 The sialic acid of human alpha 1-protease inhibitor 1083:1133 The sialic acid of human alpha 1-protease inhibitor was determined to be N-acetylneuraminic acid. 6966283 11 13 theme N-acetylneuraminic 1156:1173 arg1 acid 1175:1178 N-acetylneuraminic acid 1156:1178 N-acetylneuraminic acid 1156:1178 The sialic acid of human alpha 1-protease inhibitor was determined to be N-acetylneuraminic acid. 6966283 11 14 theme 1-protease 1114:1123 arg1 inhibitor 1125:1133 human alpha 1-protease inhibitor 1102:1133 human alpha 1-protease inhibitor 1102:1133 The sialic acid of human alpha 1-protease inhibitor was determined to be N-acetylneuraminic acid. 6966283 3 15 theme asparaginyl 204:214 arg1 protein 232:238 the protein 228:238 the protein 228:238 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 3 15 theme asparaginyl 204:214 arg1 residues 216:223 3 separate asparaginyl residues 193:223 3 separate asparaginyl residues of the protein 193:238 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 6 16 theme particular 586:595 arg1 position 597:604 this particular position 581:604 this particular position 581:604 The ratio of A-chain to B-chain in this particular position is about 2:1. 6966283 10 17 dep beta 960:963 arg1 leads 965:969 leads 965:969 leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage 965:1080 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 3 18 theme N-glycosyl 243:252 arg1 linkages 254:261 N-glycosyl linkages 243:261 N-glycosyl linkages 243:261 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 5 19 theme B-type 461:466 arg1 chain 484:488 a B-type oligosaccharide chain 459:488 a B-type oligosaccharide chain 459:488 One of the three asparaginyl residues also attaches to a B-type oligosaccharide chain, which consists of Man3, Gal3, (GlcNAc)5, and (NeuAc)3. 6966283 11 20 theme human 1102:1106 arg1 inhibitor 1125:1133 human alpha 1-protease inhibitor 1102:1133 human alpha 1-protease inhibitor 1102:1133 The sialic acid of human alpha 1-protease inhibitor was determined to be N-acetylneuraminic acid. 6966283 7 21 theme sequential 712:721 arg1 digestion 735:743 sequential glycosidase digestion 712:743 sequential glycosidase digestion 712:743 The structures of A- and B-chains of the glycoprotein were examined by periodate oxidation, sequential glycosidase digestion, and permethylation. 6966283 0 22 theme oligosaccharide 15:29 arg1 chains 31:36 the oligosaccharide chains 11:36 the oligosaccharide chains of human alpha 11:51 Studies on the oligosaccharide chains of human alpha 1-protease inhibitor. 6966283 7 23 theme periodate 691:699 arg1 oxidation 701:709 periodate oxidation 691:709 periodate oxidation 691:709 The structures of A- and B-chains of the glycoprotein were examined by periodate oxidation, sequential glycosidase digestion, and permethylation. 6966283 3 24 theme separate 195:202 arg1 protein 232:238 the protein 228:238 the protein 228:238 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 3 24 theme separate 195:202 arg1 residues 216:223 3 separate asparaginyl residues 193:223 3 separate asparaginyl residues of the protein 193:238 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 5 25 theme asparaginyl 421:431 arg1 residues 433:440 the three asparaginyl residues 411:440 the three asparaginyl residues 411:440 One of the three asparaginyl residues also attaches to a B-type oligosaccharide chain, which consists of Man3, Gal3, (GlcNAc)5, and (NeuAc)3. 6966283 4 26 attach link 302:305 arg2 Two 264:266 Two 264:266 Two 264:266 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 4 26 attach link 302:305 arg1 chains 344:349 the A-type oligosaccharide chains 317:349 the A-type oligosaccharide chains which consist of Man3, Gal2 317:377 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 4 26 attach link 302:305 arg2 residues 293:300 the three asparaginyl residues 271:300 the three asparaginyl residues 271:300 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 4 26 attach link 302:305 arg1 GlcNAc 381:386 (GlcNAc)4 380:388 (GlcNAc)4 380:388 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 4 26 attach link 302:305 arg1 NeuAc 395:399 (NeuAc)2 394:401 (NeuAc)2 394:401 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 10 27 theme NeuAc 929:933 arg1 alpha 937:941 NeuAc 2 alpha 929:941 NeuAc 2 alpha 929:941 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 8 28 theme following 805:813 arg1 structure 815:823 the following structure 801:823 the following structure for A-chains 801:836 The results unequivocally revealed the following structure for A-chains. 6966283 4 29 theme asparaginyl 281:291 arg1 residues 293:300 the three asparaginyl residues 271:300 the three asparaginyl residues 271:300 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 3 30 attach attached 181:188 arg1 protein 232:238 the protein 228:238 the protein 228:238 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 3 30 attach attached 181:188 arg2 chains 174:179 three oligosaccharide side chains 147:179 three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages 147:261 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 3 30 attach attached 181:188 arg1 residues 216:223 3 separate asparaginyl residues 193:223 3 separate asparaginyl residues of the protein 193:238 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 10 31 theme oligosaccharide 867:881 arg1 chains 883:888 B-type oligosaccharide chains 860:888 B-type oligosaccharide chains 860:888 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 6 32 theme A-chain 559:565 arg1 ratio 550:554 The ratio 546:554 The ratio of A-chain to B-chain in this particular position 546:604 The ratio of A-chain to B-chain in this particular position is about 2:1. 6966283 10 33 contain have 890:893 arg2 trisaccharide 909:921 an additional trisaccharide 895:921 an additional trisaccharide 895:921 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 10 33 contain have 890:893 arg1 chains 883:888 B-type oligosaccharide chains 860:888 B-type oligosaccharide chains 860:888 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 2 34 theme oligosaccharides 92:107 arg1 Structure 79:87 Structure 79:87 Structure of oligosaccharides. 79:108 Structure of oligosaccharides. 6966283 10 35 theme B-type 860:865 arg1 chains 883:888 B-type oligosaccharide chains 860:888 B-type oligosaccharide chains 860:888 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 3 36 theme alpha 116:120 arg1 inhibitor 133:141 Human alpha 1-protease inhibitor 110:141 Human alpha 1-protease inhibitor 110:141 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 0 37 theme alpha 47:51 arg1 chains 31:36 the oligosaccharide chains 11:36 the oligosaccharide chains of human alpha 11:51 Studies on the oligosaccharide chains of human alpha 1-protease inhibitor. 6966283 7 38 theme glycoprotein 661:672 arg1 B-chains 645:652 B-chains 645:652 B-chains 645:652 The structures of A- and B-chains of the glycoprotein were examined by periodate oxidation, sequential glycosidase digestion, and permethylation. 6966283 7 38 theme glycoprotein 661:672 arg1 A- 638:639 A- 638:639 A- 638:639 The structures of A- and B-chains of the glycoprotein were examined by periodate oxidation, sequential glycosidase digestion, and permethylation. 6966283 3 39 theme 1-protease 122:131 arg1 inhibitor 133:141 Human alpha 1-protease inhibitor 110:141 Human alpha 1-protease inhibitor 110:141 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 0 40 theme human 41:45 arg1 alpha 47:51 human alpha 41:51 human alpha 41:51 Studies on the oligosaccharide chains of human alpha 1-protease inhibitor. 6966283 7 41 theme B-chains 645:652 arg1 structures 624:633 The structures 620:633 The structures of A- and B-chains of the glycoprotein 620:672 The structures of A- and B-chains of the glycoprotein were examined by periodate oxidation, sequential glycosidase digestion, and permethylation. 6966283 10 42 from position 1025:1032 arg1 mannose 995:1001 mannose 995:1001 mannose at the (a) and/or (b) position of A-type chains 995:1049 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 6 43 from ratio 550:554 arg1 position 597:604 this particular position 581:604 this particular position 581:604 The ratio of A-chain to B-chain in this particular position is about 2:1. 6966283 10 44 theme additional 898:907 arg1 trisaccharide 909:921 an additional trisaccharide 895:921 an additional trisaccharide 895:921 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 3 45 theme Human 110:114 arg1 inhibitor 133:141 Human alpha 1-protease inhibitor 110:141 Human alpha 1-protease inhibitor 110:141 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 7 46 theme A- 638:639 arg1 structures 624:633 The structures 620:633 The structures of A- and B-chains of the glycoprotein 620:672 The structures of A- and B-chains of the glycoprotein were examined by periodate oxidation, sequential glycosidase digestion, and permethylation. 6966283 7 47 gly glycoprotein 661:672 arg1 glycoprotein 661:672 the glycoprotein 657:672 the glycoprotein 657:672 The structures of A- and B-chains of the glycoprotein were examined by periodate oxidation, sequential glycosidase digestion, and permethylation. 6966283 4 48 theme A-type 321:326 arg1 chains 344:349 the A-type oligosaccharide chains 317:349 the A-type oligosaccharide chains which consist of Man3, Gal2 317:377 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 4 48 theme A-type 321:326 arg1 NeuAc 395:399 (NeuAc)2 394:401 (NeuAc)2 394:401 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 4 48 theme A-type 321:326 arg1 GlcNAc 381:386 (GlcNAc)4 380:388 (GlcNAc)4 380:388 Two of the three asparaginyl residues link mostly to the A-type oligosaccharide chains which consist of Man3, Gal2, (GlcNAc)4 and (NeuAc)2. 6966283 7 49 theme glycosidase 723:733 arg1 digestion 735:743 sequential glycosidase digestion 712:743 sequential glycosidase digestion 712:743 The structures of A- and B-chains of the glycoprotein were examined by periodate oxidation, sequential glycosidase digestion, and permethylation. 6966283 10 50 theme a 1054:1054 arg1 beta 1056:1059 a beta 1 1054:1061 a beta 1 1054:1061 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 10 51 theme b 1022:1022 arg1 position 1025:1032 the (a) and/or (b) position 1006:1032 position 1025:1032 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 3 52 contain has 143:145 arg2 chains 174:179 three oligosaccharide side chains 147:179 three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages 147:261 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 3 52 contain has 143:145 arg1 inhibitor 133:141 Human alpha 1-protease inhibitor 110:141 Human alpha 1-protease inhibitor 110:141 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 3 53 theme oligosaccharide 153:167 arg1 chains 174:179 three oligosaccharide side chains 147:179 three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages 147:261 Human alpha 1-protease inhibitor has three oligosaccharide side chains attached to 3 separate asparaginyl residues of the protein by N-glycosyl linkages. 6966283 11 54 theme sialic 1087:1092 arg1 acid 1094:1097 The sialic acid 1083:1097 The sialic acid of human alpha 1-protease inhibitor 1083:1133 The sialic acid of human alpha 1-protease inhibitor was determined to be N-acetylneuraminic acid. 6966283 11 54 theme sialic 1087:1092 arg1 acid 1175:1178 N-acetylneuraminic acid 1156:1178 N-acetylneuraminic acid 1156:1178 The sialic acid of human alpha 1-protease inhibitor was determined to be N-acetylneuraminic acid. 6966283 10 55 attach attached 983:990 arg2 GlcNAc 976:981 4 GlcNAc 974:981 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage 974:1080 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 10 55 attach attached 983:990 arg1 mannose 995:1001 mannose 995:1001 mannose at the (a) and/or (b) position of A-type chains 995:1049 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 10 56 dep alpha 937:941 arg1 i.e. 924:927 i.e. 924:927 i.e. 924:927 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 6966283 10 57 theme a 1011:1011 arg1 position 1025:1032 the (a) and/or (b) position 1006:1032 position 1025:1032 B-type oligosaccharide chains have an additional trisaccharide, i.e. NeuAc 2 alpha leads to 3 Gal 1 beta leads to 4 GlcNAc attached to mannose at the (a) and/or (b) position of A-type chains by a beta 1 leads to 4 linkage. 7451505 1 0 theme glycoproteins 166:178 arg1 chains 143:148 the triantennary complex type sugar chains 107:148 the triantennary complex type sugar chains of human plasma glycoproteins 107:178 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins. 7451505 0 1 link asparagine-linked 22:38 arg1 chains 46:51 asparagine-linked sugar chains 22:51 asparagine-linked sugar chains of human ceruloplasmin 22:74 Structural studies of asparagine-linked sugar chains of human ceruloplasmin. 7451505 4 2 theme N-acetylneuraminic 610:627 arg1 galactose 640:648 galactose 640:648 galactose 640:648 (Formula see text) The abbreviations used are: NeuAc, N-acetylneuraminic acid; Gal, galactose; GlcNAc, N-acetylglucosamine; Man, mannose. 7451505 4 2 theme N-acetylneuraminic 610:627 arg1 NeuAc 603:607 NeuAc 603:607 NeuAc 603:607 (Formula see text) The abbreviations used are: NeuAc, N-acetylneuraminic acid; Gal, galactose; GlcNAc, N-acetylglucosamine; Man, mannose. 7451505 4 2 theme N-acetylneuraminic 610:627 arg1 acid 629:632 N-acetylneuraminic acid 610:632 N-acetylneuraminic acid 610:632 (Formula see text) The abbreviations used are: NeuAc, N-acetylneuraminic acid; Gal, galactose; GlcNAc, N-acetylglucosamine; Man, mannose. 7451505 4 2 theme N-acetylneuraminic 610:627 arg1 mannose 685:691 mannose 685:691 mannose 685:691 (Formula see text) The abbreviations used are: NeuAc, N-acetylneuraminic acid; Gal, galactose; GlcNAc, N-acetylglucosamine; Man, mannose. 7451505 4 2 theme N-acetylneuraminic 610:627 arg1 N-acetylglucosamine 659:677 N-acetylglucosamine 659:677 N-acetylglucosamine 659:677 (Formula see text) The abbreviations used are: NeuAc, N-acetylneuraminic acid; Gal, galactose; GlcNAc, N-acetylglucosamine; Man, mannose. 7451505 2 3 theme methylation 344:354 arg1 analysis 356:363 methylation analysis 344:363 methylation analysis 344:363 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis were studied by sequential exoglycosidase digestion in combination with methylation analysis and periodate oxidation. 7451505 3 4 theme oligosaccharides 452:467 arg1 structures 519:528 the structures 515:528 the structures 515:528 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 5 dep oligosaccharides 452:467 arg1 A-2 510:512 one triantennary oligosaccharide A-2 477:512 one triantennary oligosaccharide A-2 477:512 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 5 dep oligosaccharides 452:467 arg1 A-1 469:471 A-1 469:471 A-1 469:471 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 5 dep oligosaccharides 452:467 arg1 oligosaccharides 452:467 two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2 436:512 two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2 436:512 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 1 6 theme Structural 77:86 arg1 characteristics 88:102 Structural characteristics 77:102 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins 77:178 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins. 7451505 3 7 theme ceruloplasmin 404:416 arg1 molecule 392:399 A molecule 390:399 A molecule of ceruloplasmin 390:416 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 8 contain have 431:434 arg2 A-1 469:471 A-1 469:471 A-1 469:471 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 8 contain have 431:434 arg1 molecule 392:399 A molecule 390:399 A molecule of ceruloplasmin 390:416 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 8 contain have 431:434 arg2 oligosaccharides 452:467 two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2 436:512 two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2 436:512 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 8 contain have 431:434 arg2 A-2 510:512 one triantennary oligosaccharide A-2 477:512 one triantennary oligosaccharide A-2 477:512 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 9 theme biantennary 440:450 arg1 A-2 510:512 one triantennary oligosaccharide A-2 477:512 one triantennary oligosaccharide A-2 477:512 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 9 theme biantennary 440:450 arg1 A-1 469:471 A-1 469:471 A-1 469:471 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 9 theme biantennary 440:450 arg1 oligosaccharides 452:467 two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2 436:512 two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2 436:512 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 2 10 theme periodate 369:377 arg1 oxidation 379:387 periodate oxidation 369:387 periodate oxidation 369:387 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis were studied by sequential exoglycosidase digestion in combination with methylation analysis and periodate oxidation. 7451505 3 11 theme triantennary 481:492 arg1 A-2 510:512 one triantennary oligosaccharide A-2 477:512 one triantennary oligosaccharide A-2 477:512 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 11 theme triantennary 481:492 arg1 oligosaccharides 452:467 two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2 436:512 two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2 436:512 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 0 12 theme Structural 0:9 arg1 studies 11:17 Structural studies 0:17 Structural studies of asparagine-linked sugar chains of human ceruloplasmin 0:74 Structural studies of asparagine-linked sugar chains of human ceruloplasmin. 7451505 2 13 attach released 220:227 arg1 ceruloplasmin 240:252 human ceruloplasmin 234:252 human ceruloplasmin 234:252 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis were studied by sequential exoglycosidase digestion in combination with methylation analysis and periodate oxidation. 7451505 2 13 attach released 220:227 arg2 oligosaccharides 203:218 the oligosaccharides 199:218 the oligosaccharides released from human ceruloplasmin by hydrazinolysis 199:270 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis were studied by sequential exoglycosidase digestion in combination with methylation analysis and periodate oxidation. 7451505 0 14 theme asparagine-linked 22:38 arg1 chains 46:51 asparagine-linked sugar chains 22:51 asparagine-linked sugar chains of human ceruloplasmin 22:74 Structural studies of asparagine-linked sugar chains of human ceruloplasmin. 7451505 1 15 theme triantennary 111:122 arg1 chains 143:148 the triantennary complex type sugar chains 107:148 the triantennary complex type sugar chains of human plasma glycoproteins 107:178 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins. 7451505 1 16 theme complex 124:130 arg1 chains 143:148 the triantennary complex type sugar chains 107:148 the triantennary complex type sugar chains of human plasma glycoproteins 107:178 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins. 7451505 0 17 theme chains 46:51 arg1 studies 11:17 Structural studies 0:17 Structural studies of asparagine-linked sugar chains of human ceruloplasmin 0:74 Structural studies of asparagine-linked sugar chains of human ceruloplasmin. 7451505 3 18 theme oligosaccharide 494:508 arg1 A-2 510:512 one triantennary oligosaccharide A-2 477:512 one triantennary oligosaccharide A-2 477:512 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 3 18 theme oligosaccharide 494:508 arg1 oligosaccharides 452:467 two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2 436:512 two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2 436:512 A molecule of ceruloplasmin was shown to have two biantennary oligosaccharides A-1 and one triantennary oligosaccharide A-2, the structures of which are shown below. 7451505 0 19 theme sugar 40:44 arg1 chains 46:51 asparagine-linked sugar chains 22:51 asparagine-linked sugar chains of human ceruloplasmin 22:74 Structural studies of asparagine-linked sugar chains of human ceruloplasmin. 7451505 4 20 dep acid 629:632 arg1 Gal 635:637 Gal 635:637 Gal 635:637 (Formula see text) The abbreviations used are: NeuAc, N-acetylneuraminic acid; Gal, galactose; GlcNAc, N-acetylglucosamine; Man, mannose. 7451505 4 20 dep acid 629:632 arg1 Man 680:682 Man 680:682 Man 680:682 (Formula see text) The abbreviations used are: NeuAc, N-acetylneuraminic acid; Gal, galactose; GlcNAc, N-acetylglucosamine; Man, mannose. 7451505 4 20 dep acid 629:632 arg1 GlcNAc 651:656 GlcNAc 651:656 GlcNAc 651:656 (Formula see text) The abbreviations used are: NeuAc, N-acetylneuraminic acid; Gal, galactose; GlcNAc, N-acetylglucosamine; Man, mannose. 7451505 0 21 theme human 56:60 arg1 ceruloplasmin 62:74 human ceruloplasmin 56:74 human ceruloplasmin 56:74 Structural studies of asparagine-linked sugar chains of human ceruloplasmin. 7451505 1 22 theme type 132:135 arg1 chains 143:148 the triantennary complex type sugar chains 107:148 the triantennary complex type sugar chains of human plasma glycoproteins 107:178 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins. 7451505 2 23 theme human 234:238 arg1 ceruloplasmin 240:252 human ceruloplasmin 234:252 human ceruloplasmin 234:252 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis were studied by sequential exoglycosidase digestion in combination with methylation analysis and periodate oxidation. 7451505 1 24 theme sugar 137:141 arg1 chains 143:148 the triantennary complex type sugar chains 107:148 the triantennary complex type sugar chains of human plasma glycoproteins 107:178 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins. 7451505 2 25 theme exoglycosidase 299:312 arg1 digestion 314:322 sequential exoglycosidase digestion 288:322 sequential exoglycosidase digestion 288:322 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis were studied by sequential exoglycosidase digestion in combination with methylation analysis and periodate oxidation. 7451505 1 26 theme chains 143:148 arg1 characteristics 88:102 Structural characteristics 77:102 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins 77:178 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins. 7451505 1 27 gly glycoproteins 166:178 arg1 glycoproteins 166:178 human plasma glycoproteins 153:178 human plasma glycoproteins 153:178 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins. 7451505 2 28 theme sequential 288:297 arg1 digestion 314:322 sequential exoglycosidase digestion 288:322 sequential exoglycosidase digestion 288:322 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis were studied by sequential exoglycosidase digestion in combination with methylation analysis and periodate oxidation. 7451505 2 29 theme oligosaccharides 203:218 arg1 structures 185:194 The structures 181:194 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis 181:270 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis were studied by sequential exoglycosidase digestion in combination with methylation analysis and periodate oxidation. 7451505 1 30 theme human 153:157 arg1 glycoproteins 166:178 human plasma glycoproteins 153:178 human plasma glycoproteins 153:178 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins. 7451505 0 31 theme ceruloplasmin 62:74 arg1 chains 46:51 asparagine-linked sugar chains 22:51 asparagine-linked sugar chains of human ceruloplasmin 22:74 Structural studies of asparagine-linked sugar chains of human ceruloplasmin. 7451505 1 32 theme plasma 159:164 arg1 glycoproteins 166:178 human plasma glycoproteins 153:178 human plasma glycoproteins 153:178 Structural characteristics of the triantennary complex type sugar chains of human plasma glycoproteins. 7451505 2 33 with combination 327:337 arg1 analysis 356:363 methylation analysis 344:363 methylation analysis 344:363 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis were studied by sequential exoglycosidase digestion in combination with methylation analysis and periodate oxidation. 7451505 2 33 with combination 327:337 arg1 oxidation 379:387 periodate oxidation 369:387 periodate oxidation 369:387 The structures of the oligosaccharides released from human ceruloplasmin by hydrazinolysis were studied by sequential exoglycosidase digestion in combination with methylation analysis and periodate oxidation. 1374031 9 0 theme normal 1640:1645 arg1 hCG 1655:1657 normal urinary hCG 1640:1657 normal urinary hCG 1640:1657 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 1 theme tetrasaccharide 1442:1456 arg1 alpha 1494:1498 Neu5Ac alpha 2-6 1487:1502 Neu5Ac alpha 2-6 1487:1502 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 1 theme tetrasaccharide 1442:1456 arg1 beta 1478:1481 tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3 1442:1485 the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol 1438:1512 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 2 theme Neu5Ac 1581:1586 arg1 beta 1572:1575 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6 1518:1579 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3) 1518:1609 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 2 theme Neu5Ac 1581:1586 arg1 beta 1601:1604 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 3 3 theme carbohydrate 596:607 arg1 chains 609:614 The carbohydrate chains 592:614 The carbohydrate chains 592:614 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 9 4 theme alpha 1465:1469 arg1 alpha 1494:1498 Neu5Ac alpha 2-6 1487:1502 Neu5Ac alpha 2-6 1487:1502 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 4 theme alpha 1465:1469 arg1 beta 1478:1481 tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3 1442:1485 the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol 1438:1512 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 4 5 theme N-linked 933:940 arg1 oligosaccharides 942:957 the following sialylated diantennary and triantennary N-linked oligosaccharides 879:957 oligosaccharides 942:957 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 8 6 theme GlcNAc 1268:1273 arg1 presence 1244:1251 The presence 1240:1251 The presence of a bisecting GlcNAc 1240:1273 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 8 6 theme GlcNAc 1268:1273 arg1 features 1361:1368 new features 1357:1368 new features for hCG-beta 1357:1381 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 8 6 theme GlcNAc 1268:1273 arg1 occurrence 1283:1292 the occurrence 1279:1292 the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans 1279:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 9 7 theme beta 1478:1481 arg1 GalNAc-ol 1504:1512 the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol 1438:1512 the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol 1438:1512 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 6 8 theme triantennary 1056:1067 arg1 chains 1082:1087 triantennary carbohydrate chains 1056:1087 triantennary carbohydrate chains 1056:1087 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 9 9 theme 2-3Gal 1471:1476 arg1 alpha 1494:1498 Neu5Ac alpha 2-6 1487:1502 Neu5Ac alpha 2-6 1487:1502 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 9 theme 2-3Gal 1471:1476 arg1 beta 1478:1481 tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3 1442:1485 the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol 1438:1512 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 7 10 gly 1-6-fucosylation 1178:1193 arg1 GlcNAc 1219:1224 the asparagine-bound GlcNAc 1198:1224 the asparagine-bound GlcNAc (95% vs 42%) 1198:1237 The same holds for the alpha 1-6-fucosylation of the asparagine-bound GlcNAc (95% vs 42%). 1374031 4 11 dep diantennary 904:914 arg1 sialylated 893:902 sialylated 893:902 sialylated 893:902 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 4 11 dep diantennary 904:914 arg1 following 883:891 following 883:891 following 883:891 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 8 12 theme 2-6-linked 1303:1312 arg1 Neu5Ac 1314:1319 alpha 2-6-linked Neu5Ac 1297:1319 alpha 2-6-linked Neu5Ac in the most abundant N-glycans 1297:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 2 13 theme subunit 246:252 arg1 chains 227:232 The N-linked carbohydrate chains 201:232 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo 201:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 3 14 from chromatography 763:776 arg1 Q 709:709 Mono Q 704:709 Mono Q 704:709 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 3 14 from chromatography 763:776 arg1 PA1 790:792 CarboPac PA1 781:792 CarboPac PA1 781:792 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 3 14 from chromatography 763:776 arg1 Lichrosorb-NH2 720:733 Lichrosorb-NH2 720:733 Lichrosorb-NH2 720:733 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 3 15 theme intact 639:644 arg1 forms 657:661 their intact sialylated forms 633:661 their intact sialylated forms 633:661 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 10 16 dep characterized 1698:1710 arg1 [formula 1713:1720 [formula 1713:1720 [formula: see text] 1713:1731 In addition, two novel O-glycans were characterized: [formula: see text] 1374031 2 17 theme gonadotropin 273:284 arg1 subunit 246:252 the beta subunit 237:252 the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo 237:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 9 18 theme hexasaccharide 1522:1535 arg1 beta 1572:1575 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6 1518:1579 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3) 1518:1609 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 18 theme hexasaccharide 1522:1535 arg1 beta 1601:1604 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 6 19 theme normal 1112:1117 arg1 hCG-beta 1127:1134 normal urinary hCG-beta 1112:1134 normal urinary hCG-beta (26% vs 2%) 1112:1146 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 0 20 theme human 47:51 arg1 gonadotropin 63:74 human chorionic gonadotropin 47:74 human chorionic gonadotropin 47:74 The carbohydrate chains of the beta subunit of human chorionic gonadotropin produced by the choriocarcinoma cell line BeWo. 1374031 3 21 theme FPLC 666:669 arg1 chromatography 686:699 FPLC anion-exchange chromatography 666:699 FPLC anion-exchange chromatography on Mono Q 666:709 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 9 22 theme alpha 1544:1548 arg1 beta 1572:1575 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6 1518:1579 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3) 1518:1609 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 22 theme alpha 1544:1548 arg1 beta 1601:1604 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 0 23 theme gonadotropin 63:74 arg1 subunit 36:42 the beta subunit 27:42 the beta subunit of human chorionic gonadotropin 27:74 The carbohydrate chains of the beta subunit of human chorionic gonadotropin produced by the choriocarcinoma cell line BeWo. 1374031 0 24 dep line 113:116 arg1 BeWo 118:121 BeWo 118:121 the choriocarcinoma cell line BeWo 88:121 The carbohydrate chains of the beta subunit of human chorionic gonadotropin produced by the choriocarcinoma cell line BeWo. 1374031 2 25 theme borohydride 569:579 arg1 treatment 581:589 mild alkaline borohydride treatment 555:589 mild alkaline borohydride treatment 555:589 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 4 26 theme major 832:836 arg1 fractions 838:846 the major fractions 828:846 the major fractions 828:846 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 6 27 theme chains 1082:1087 arg1 higher 1097:1102 higher 1097:1102 higher 1097:1102 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 6 27 theme chains 1082:1087 arg1 incidence 1043:1051 The incidence 1039:1051 The incidence of triantennary carbohydrate chains 1039:1087 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 2 28 theme mild 555:558 arg1 treatment 581:589 mild alkaline borohydride treatment 555:589 mild alkaline borohydride treatment 555:589 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 2 29 theme N-acetyl-beta-glucosaminyl 410:435 arg1 amidase 448:454 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 398:457 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 398:457 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 0 30 theme choriocarcinoma 92:106 arg1 line 113:116 choriocarcinoma cell line 92:116 the choriocarcinoma cell line BeWo 88:121 The carbohydrate chains of the beta subunit of human chorionic gonadotropin produced by the choriocarcinoma cell line BeWo. 1374031 0 31 theme beta 31:34 arg1 subunit 36:42 the beta subunit 27:42 the beta subunit of human chorionic gonadotropin 27:74 The carbohydrate chains of the beta subunit of human chorionic gonadotropin produced by the choriocarcinoma cell line BeWo. 1374031 2 32 theme O-linked 477:484 arg1 split 508:512 split 508:512 split 508:512 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 2 32 theme O-linked 477:484 arg1 oligosaccharides 486:501 the O-linked oligosaccharides 473:501 the O-linked oligosaccharides 473:501 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 1 33 link N-linked 177:184 arg1 carbohydrates 186:198 Novel O-linked and novel bisecting-GlcNAc-containing N-linked carbohydrates 124:198 carbohydrates 186:198 Novel O-linked and novel bisecting-GlcNAc-containing N-linked carbohydrates. 1374031 4 34 theme spectroscopic 802:814 arg1 analysis 816:823 1H-NMR spectroscopic analysis 795:823 1H-NMR spectroscopic analysis of the major fractions 795:846 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 3 35 from chromatography 686:699 arg1 Q 709:709 Mono Q 704:709 Mono Q 704:709 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 3 35 from chromatography 686:699 arg1 PA1 790:792 CarboPac PA1 781:792 CarboPac PA1 781:792 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 3 35 from chromatography 686:699 arg1 Lichrosorb-NH2 720:733 Lichrosorb-NH2 720:733 Lichrosorb-NH2 720:733 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 2 36 theme peptide-N4- 398:408 arg1 amidase 448:454 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 398:457 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 398:457 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 8 37 from N-glycans 1342:1350 arg1 presence 1244:1251 The presence 1240:1251 The presence of a bisecting GlcNAc 1240:1273 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 8 37 from N-glycans 1342:1350 arg1 features 1361:1368 new features 1357:1368 new features for hCG-beta 1357:1381 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 8 37 from N-glycans 1342:1350 arg1 occurrence 1283:1292 the occurrence 1279:1292 the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans 1279:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 9 38 theme alpha 1588:1592 arg1 beta 1572:1575 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6 1518:1579 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3) 1518:1609 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 38 theme alpha 1588:1592 arg1 beta 1601:1604 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 2 39 dep line 357:360 arg1 BeWo 362:365 BeWo 362:365 the choriocarcinoma cell line BeWo 332:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 9 40 theme Neu5Ac 1537:1542 arg1 beta 1572:1575 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6 1518:1579 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3) 1518:1609 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 40 theme Neu5Ac 1537:1542 arg1 beta 1601:1604 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 2 41 theme asparagine 437:446 arg1 amidase 448:454 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 398:457 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 398:457 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 7 42 theme GlcNAc 1219:1224 arg1 1-6-fucosylation 1178:1193 the alpha 1-6-fucosylation 1168:1193 the alpha 1-6-fucosylation of the asparagine-bound GlcNAc (95% vs 42%) 1168:1237 The same holds for the alpha 1-6-fucosylation of the asparagine-bound GlcNAc (95% vs 42%). 1374031 3 43 theme Mono 704:707 arg1 Q 709:709 Mono Q 704:709 Mono Q 704:709 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 2 44 theme line 357:360 arg1 fluid 323:327 the culture fluid 311:327 the culture fluid of the choriocarcinoma cell line BeWo 311:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 0 45 theme subunit 36:42 arg1 chains 17:22 The carbohydrate chains 0:22 The carbohydrate chains of the beta subunit of human chorionic gonadotropin 0:74 The carbohydrate chains of the beta subunit of human chorionic gonadotropin produced by the choriocarcinoma cell line BeWo. 1374031 9 46 theme major 1388:1392 arg1 chains 1416:1421 The major O-linked carbohydrate chains 1384:1421 The major O-linked carbohydrate chains identified 1384:1432 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 8 47 link 2-6-linked 1303:1312 arg1 Neu5Ac 1314:1319 alpha 2-6-linked Neu5Ac 1297:1319 alpha 2-6-linked Neu5Ac in the most abundant N-glycans 1297:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 2 48 theme human 257:261 arg1 hCG-beta 287:294 hCG-beta 287:294 hCG-beta 287:294 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 2 48 theme human 257:261 arg1 gonadotropin 273:284 human chorionic gonadotropin 257:284 human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo 257:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 2 49 theme choriocarcinoma 336:350 arg1 line 357:360 the choriocarcinoma cell line 332:360 the choriocarcinoma cell line BeWo 332:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 9 50 theme carbohydrate 1403:1414 arg1 chains 1416:1421 The major O-linked carbohydrate chains 1384:1421 The major O-linked carbohydrate chains identified 1384:1432 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 3 51 from HPLC 712:715 arg1 Q 709:709 Mono Q 704:709 Mono Q 704:709 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 3 51 from HPLC 712:715 arg1 PA1 790:792 CarboPac PA1 781:792 CarboPac PA1 781:792 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 3 51 from HPLC 712:715 arg1 Lichrosorb-NH2 720:733 Lichrosorb-NH2 720:733 Lichrosorb-NH2 720:733 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 2 52 theme N-linked 205:212 arg1 chains 227:232 The N-linked carbohydrate chains 201:232 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo 201:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 7 53 theme alpha 1172:1176 arg1 1-6-fucosylation 1178:1193 the alpha 1-6-fucosylation 1168:1193 the alpha 1-6-fucosylation of the asparagine-bound GlcNAc (95% vs 42%) 1168:1237 The same holds for the alpha 1-6-fucosylation of the asparagine-bound GlcNAc (95% vs 42%). 1374031 9 54 theme urinary 1647:1653 arg1 hCG 1655:1657 normal urinary hCG 1640:1657 normal urinary hCG 1640:1657 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 3 55 theme high-pH 740:746 arg1 chromatography 763:776 high-pH anion-exchange chromatography 740:776 high-pH anion-exchange chromatography on CarboPac PA1 740:792 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 9 56 theme Neu5Ac 1458:1463 arg1 alpha 1494:1498 Neu5Ac alpha 2-6 1487:1502 Neu5Ac alpha 2-6 1487:1502 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 56 theme Neu5Ac 1458:1463 arg1 beta 1478:1481 tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3 1442:1485 the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol 1438:1512 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 57 theme 2-3Gal 1550:1555 arg1 beta 1572:1575 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6 1518:1579 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3) 1518:1609 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 57 theme 2-3Gal 1550:1555 arg1 beta 1601:1604 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 6 58 dep [formula 1019:1026 arg1 see 1029:1031 see 1029:1031 see text 1029:1036 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 6 58 dep [formula 1019:1026 arg1 higher 1097:1102 higher 1097:1102 higher 1097:1102 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 6 58 dep [formula 1019:1026 arg1 incidence 1043:1051 The incidence 1039:1051 The incidence of triantennary carbohydrate chains 1039:1087 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 1 59 theme N-linked 177:184 arg1 carbohydrates 186:198 Novel O-linked and novel bisecting-GlcNAc-containing N-linked carbohydrates 124:198 carbohydrates 186:198 Novel O-linked and novel bisecting-GlcNAc-containing N-linked carbohydrates. 1374031 8 60 from presence 1244:1251 arg1 N-glycans 1342:1350 the most abundant N-glycans 1324:1350 the most abundant N-glycans 1324:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 4 61 theme triantennary 920:931 arg1 oligosaccharides 942:957 the following sialylated diantennary and triantennary N-linked oligosaccharides 879:957 oligosaccharides 942:957 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 8 62 theme bisecting 1258:1266 arg1 GlcNAc 1268:1273 a bisecting GlcNAc 1256:1273 a bisecting GlcNAc 1256:1273 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 3 63 theme CarboPac 781:788 arg1 PA1 790:792 CarboPac PA1 781:792 CarboPac PA1 781:792 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 6 64 theme carbohydrate 1069:1080 arg1 chains 1082:1087 triantennary carbohydrate chains 1056:1087 triantennary carbohydrate chains 1056:1087 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 4 65 theme oligosaccharides 942:957 arg1 occurrence 865:874 the occurrence 861:874 the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides 861:957 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 2 66 dep amidase 448:454 arg1 F. 456:457 F. 456:457 F. 456:457 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 2 67 theme culture 315:321 arg1 fluid 323:327 the culture fluid 311:327 the culture fluid of the choriocarcinoma cell line BeWo 311:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 9 68 theme Neu5Ac 1487:1492 arg1 alpha 1494:1498 Neu5Ac alpha 2-6 1487:1502 Neu5Ac alpha 2-6 1487:1502 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 68 theme Neu5Ac 1487:1492 arg1 beta 1478:1481 tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3 1442:1485 the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol 1438:1512 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 1 69 theme bisecting-GlcNAc-containing 149:175 arg1 carbohydrates 186:198 Novel O-linked and novel bisecting-GlcNAc-containing N-linked carbohydrates 124:198 carbohydrates 186:198 Novel O-linked and novel bisecting-GlcNAc-containing N-linked carbohydrates. 1374031 9 70 theme beta 1557:1560 arg1 beta 1572:1575 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6 1518:1579 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3) 1518:1609 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 70 theme beta 1557:1560 arg1 beta 1601:1604 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 3 71 gly sialylated 646:655 arg1 forms 657:661 their intact sialylated forms 633:661 their intact sialylated forms 633:661 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 3 72 theme sialylated 646:655 arg1 forms 657:661 their intact sialylated forms 633:661 their intact sialylated forms 633:661 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 2 73 attach isolated 297:304 arg2 hCG-beta 287:294 hCG-beta 287:294 hCG-beta 287:294 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 2 73 attach isolated 297:304 arg2 gonadotropin 273:284 human chorionic gonadotropin 257:284 human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo 257:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 2 73 attach isolated 297:304 arg1 fluid 323:327 the culture fluid 311:327 the culture fluid of the choriocarcinoma cell line BeWo 311:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 8 74 theme alpha 1297:1301 arg1 Neu5Ac 1314:1319 alpha 2-6-linked Neu5Ac 1297:1319 alpha 2-6-linked Neu5Ac in the most abundant N-glycans 1297:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 4 75 link N-linked 933:940 arg1 oligosaccharides 942:957 the following sialylated diantennary and triantennary N-linked oligosaccharides 879:957 oligosaccharides 942:957 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 2 76 theme beta 241:244 arg1 subunit 246:252 the beta subunit 237:252 the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo 237:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 8 77 theme Neu5Ac 1314:1319 arg1 presence 1244:1251 The presence 1240:1251 The presence of a bisecting GlcNAc 1240:1273 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 8 77 theme Neu5Ac 1314:1319 arg1 features 1361:1368 new features 1357:1368 new features for hCG-beta 1357:1381 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 8 77 theme Neu5Ac 1314:1319 arg1 occurrence 1283:1292 the occurrence 1279:1292 the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans 1279:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 3 78 theme anion-exchange 671:684 arg1 chromatography 686:699 FPLC anion-exchange chromatography 666:699 FPLC anion-exchange chromatography on Mono Q 666:709 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1374031 6 79 theme urinary 1119:1125 arg1 hCG-beta 1127:1134 normal urinary hCG-beta 1112:1134 normal urinary hCG-beta (26% vs 2%) 1112:1146 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 10 80 dep [formula 1713:1720 arg1 see 1723:1725 see 1723:1725 see text 1723:1730 In addition, two novel O-glycans were characterized: [formula: see text] 1374031 0 81 theme chorionic 53:61 arg1 gonadotropin 63:74 human chorionic gonadotropin 47:74 human chorionic gonadotropin 47:74 The carbohydrate chains of the beta subunit of human chorionic gonadotropin produced by the choriocarcinoma cell line BeWo. 1374031 2 82 theme chorionic 263:271 arg1 hCG-beta 287:294 hCG-beta 287:294 hCG-beta 287:294 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 2 82 theme chorionic 263:271 arg1 gonadotropin 273:284 human chorionic gonadotropin 257:284 human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo 257:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 9 83 dep found 1631:1635 arg1 both 1621:1624 both 1621:1624 both 1621:1624 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 5 84 theme bold 984:987 arg1 letters 989:995 bold letters 984:995 bold letters 984:995 Residues not written in bold letters are variably present. 1374031 2 85 theme N-deglycosylated 527:542 arg1 protein 544:550 the N-deglycosylated protein 523:550 the N-deglycosylated protein 523:550 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 8 86 theme abundant 1333:1340 arg1 N-glycans 1342:1350 the most abundant N-glycans 1324:1350 the most abundant N-glycans 1324:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 8 87 from occurrence 1283:1292 arg1 N-glycans 1342:1350 the most abundant N-glycans 1324:1350 the most abundant N-glycans 1324:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 1 88 theme novel 143:147 arg1 carbohydrates 186:198 Novel O-linked and novel bisecting-GlcNAc-containing N-linked carbohydrates 124:198 carbohydrates 186:198 Novel O-linked and novel bisecting-GlcNAc-containing N-linked carbohydrates. 1374031 9 89 theme 1-4GlcNAc 1562:1570 arg1 beta 1572:1575 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6 1518:1579 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3) 1518:1609 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 89 theme 1-4GlcNAc 1562:1570 arg1 beta 1601:1604 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 2 90 theme alkaline 560:567 arg1 treatment 581:589 mild alkaline borohydride treatment 555:589 mild alkaline borohydride treatment 555:589 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 8 91 theme new 1357:1359 arg1 presence 1244:1251 The presence 1240:1251 The presence of a bisecting GlcNAc 1240:1273 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 8 91 theme new 1357:1359 arg1 features 1361:1368 new features 1357:1368 new features for hCG-beta 1357:1381 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 8 91 theme new 1357:1359 arg1 occurrence 1283:1292 the occurrence 1279:1292 the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans 1279:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 2 92 link O-linked 477:484 arg1 split 508:512 split 508:512 split 508:512 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 2 92 link O-linked 477:484 arg1 oligosaccharides 486:501 the O-linked oligosaccharides 473:501 the O-linked oligosaccharides 473:501 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 6 93 dep hCG-beta 1127:1134 arg1 % 1139:1139 26% 1137:1139 26% 1137:1139 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 6 93 dep hCG-beta 1127:1134 arg1 % 1145:1145 2% 1144:1145 2% 1144:1145 [formula: see text] The incidence of triantennary carbohydrate chains is much higher than in normal urinary hCG-beta (26% vs 2%). 1374031 0 94 theme cell 108:111 arg1 line 113:116 choriocarcinoma cell line 92:116 the choriocarcinoma cell line BeWo 88:121 The carbohydrate chains of the beta subunit of human chorionic gonadotropin produced by the choriocarcinoma cell line BeWo. 1374031 8 95 from Neu5Ac 1314:1319 arg1 N-glycans 1342:1350 the most abundant N-glycans 1324:1350 the most abundant N-glycans 1324:1350 The presence of a bisecting GlcNAc and the occurrence of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for hCG-beta. 1374031 4 96 theme fractions 838:846 arg1 analysis 816:823 1H-NMR spectroscopic analysis 795:823 1H-NMR spectroscopic analysis of the major fractions 795:846 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 0 97 theme carbohydrate 4:15 arg1 chains 17:22 The carbohydrate chains 0:22 The carbohydrate chains of the beta subunit of human chorionic gonadotropin 0:74 The carbohydrate chains of the beta subunit of human chorionic gonadotropin produced by the choriocarcinoma cell line BeWo. 1374031 2 98 gly N-deglycosylated 527:542 arg1 protein 544:550 the N-deglycosylated protein 523:550 the N-deglycosylated protein 523:550 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 7 99 dep GlcNAc 1219:1224 arg1 % 1229:1229 95% 1227:1229 95% 1227:1229 The same holds for the alpha 1-6-fucosylation of the asparagine-bound GlcNAc (95% vs 42%). 1374031 7 99 dep GlcNAc 1219:1224 arg1 % 1236:1236 42% 1234:1236 42% 1234:1236 The same holds for the alpha 1-6-fucosylation of the asparagine-bound GlcNAc (95% vs 42%). 1374031 4 100 theme 1H-NMR 795:800 arg1 analysis 816:823 1H-NMR spectroscopic analysis 795:823 1H-NMR spectroscopic analysis of the major fractions 795:846 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 9 101 theme 2-3Gal 1594:1599 arg1 beta 1572:1575 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6 1518:1579 the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3) 1518:1609 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 101 theme 2-3Gal 1594:1599 arg1 beta 1601:1604 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 Neu5Ac alpha 2-3Gal beta 1-3 1581:1608 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 2 102 link N-linked 205:212 arg1 chains 227:232 The N-linked carbohydrate chains 201:232 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo 201:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 7 103 theme asparagine-bound 1202:1217 arg1 GlcNAc 1219:1224 the asparagine-bound GlcNAc 1198:1224 the asparagine-bound GlcNAc (95% vs 42%) 1198:1237 The same holds for the alpha 1-6-fucosylation of the asparagine-bound GlcNAc (95% vs 42%). 1374031 9 104 link O-linked 1394:1401 arg1 chains 1416:1421 The major O-linked carbohydrate chains 1384:1421 The major O-linked carbohydrate chains identified 1384:1432 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 105 located found 1631:1635 arg1 hCG 1655:1657 normal urinary hCG 1640:1657 normal urinary hCG 1640:1657 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 9 105 located found 1631:1635 arg2 chains 1416:1421 The major O-linked carbohydrate chains 1384:1421 The major O-linked carbohydrate chains identified 1384:1432 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 4 106 theme diantennary 904:914 arg1 occurrence 865:874 the occurrence 861:874 the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides 861:957 1H-NMR spectroscopic analysis of the major fractions demonstrates the occurrence of the following sialylated diantennary and triantennary N-linked oligosaccharides. 1374031 2 107 theme cell 352:355 arg1 line 357:360 the choriocarcinoma cell line 332:360 the choriocarcinoma cell line BeWo 332:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 9 108 theme O-linked 1394:1401 arg1 chains 1416:1421 The major O-linked carbohydrate chains 1384:1421 The major O-linked carbohydrate chains identified 1384:1432 The major O-linked carbohydrate chains identified are the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal beta 1-3)GalNAc-ol, both also found in normal urinary hCG. 1374031 2 109 dep protein 544:550 arg1 off 514:516 off 514:516 off 514:516 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 2 110 theme carbohydrate 214:225 arg1 chains 227:232 The N-linked carbohydrate chains 201:232 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo 201:365 The N-linked carbohydrate chains of the beta subunit of human chorionic gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides were split off from the N-deglycosylated protein by mild alkaline borohydride treatment. 1374031 10 111 theme novel 1677:1681 arg1 O-glycans 1683:1691 two novel O-glycans 1673:1691 two novel O-glycans 1673:1691 In addition, two novel O-glycans were characterized: [formula: see text] 1374031 3 112 theme anion-exchange 748:761 arg1 chromatography 763:776 high-pH anion-exchange chromatography 740:776 high-pH anion-exchange chromatography on CarboPac PA1 740:792 The carbohydrate chains were purified in their intact sialylated forms by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1935941 5 0 dep residues 756:763 arg1 to 743:744 to 743:744 to 743:744 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 1 theme X 715:715 arg1 residues 705:712 GlcNAc residues 698:712 GlcNAc residues (X determinant) 698:728 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 1 theme X 715:715 arg1 determinant 717:727 X determinant 715:727 X determinant 715:727 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 6 2 theme N-glycosidically 895:910 arg1 glycans 919:925 N-glycosidically linked glycans 895:925 N-glycosidically linked glycans of the N-acetyllactosamine type 895:957 The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. 1935941 3 3 theme incomplete 396:405 arg1 catabolism 407:416 the incomplete catabolism 392:416 the incomplete catabolism of N-glycosidically linked glycans 392:451 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 0 4 from Characterization 0:15 arg1 fucosidosis 84:94 fucosidosis 84:94 fucosidosis 84:94 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 1 5 with patient 153:159 arg1 fucosidosis 166:176 fucosidosis 166:176 fucosidosis 166:176 Fucosyl glycoasparagines accumulating in the urine of a patient with fucosidosis were isolated using reverse-phase HPLC. 1935941 2 6 theme 1H-NMR 319:324 arg1 spectroscopy 326:337 400-MHz 1H-NMR spectroscopy 311:337 400-MHz 1H-NMR spectroscopy 311:337 Structural analysis of 25 glycoasparagines was carried out by combination of methylation and 400-MHz 1H-NMR spectroscopy analyses. 1935941 4 7 attach attached 599:606 arg1 asparagine 611:620 asparagine 611:620 asparagine 611:620 All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. 1935941 4 7 attach attached 599:606 arg2 residue 591:597 the GlcNAc 1 residue 578:597 the GlcNAc 1 residue attached to asparagine 578:620 All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. 1935941 6 8 theme precise 807:813 arg1 assignments 815:825 precise assignments 807:825 precise assignments of the NMR parameters 807:847 The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. 1935941 2 9 theme 400-MHz 311:317 arg1 spectroscopy 326:337 400-MHz 1H-NMR spectroscopy 311:337 400-MHz 1H-NMR spectroscopy 311:337 Structural analysis of 25 glycoasparagines was carried out by combination of methylation and 400-MHz 1H-NMR spectroscopy analyses. 1935941 6 10 theme type 954:957 arg1 glycans 919:925 N-glycosidically linked glycans 895:925 N-glycosidically linked glycans of the N-acetyllactosamine type 895:957 The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. 1935941 3 11 theme alpha-L-fucosidase 474:491 arg1 deficiency 493:502 an alpha-L-fucosidase deficiency 471:502 an alpha-L-fucosidase deficiency 471:502 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 4 12 theme fucose 543:548 arg1 residue 550:556 a fucose residue 541:556 a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine 541:620 All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. 1935941 6 13 theme parameters 838:847 arg1 assignments 815:825 precise assignments 807:825 precise assignments of the NMR parameters 807:847 The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. 1935941 2 14 theme methylation 295:305 arg1 combination 280:290 combination 280:290 combination of methylation and 400-MHz 1H-NMR spectroscopy analyses 280:346 Structural analysis of 25 glycoasparagines was carried out by combination of methylation and 400-MHz 1H-NMR spectroscopy analyses. 1935941 3 15 theme deficiency 493:502 arg1 steps 383:387 different steps 373:387 different steps in the incomplete catabolism of N-glycosidically linked glycans 373:451 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 3 15 theme deficiency 493:502 arg1 result 461:466 the result 457:466 the result of an alpha-L-fucosidase deficiency 457:502 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 3 16 theme linked 438:443 arg1 glycans 445:451 N-glycosidically linked glycans 421:451 N-glycosidically linked glycans 421:451 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 0 17 from analysis 36:43 arg1 fucosidosis 84:94 fucosidosis 84:94 fucosidosis 84:94 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 5 18 theme GlcNAc 698:703 arg1 residues 705:712 GlcNAc residues 698:712 GlcNAc residues (X determinant) 698:728 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 18 theme GlcNAc 698:703 arg1 determinant 717:727 X determinant 715:727 X determinant 715:727 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 6 19 theme NMR 834:836 arg1 parameters 838:847 the NMR parameters 830:847 the NMR parameters 830:847 The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. 1935941 1 20 theme Fucosyl 97:103 arg1 glycoasparagines 105:120 Fucosyl glycoasparagines 97:120 Fucosyl glycoasparagines accumulating in the urine of a patient with fucosidosis 97:176 Fucosyl glycoasparagines accumulating in the urine of a patient with fucosidosis were isolated using reverse-phase HPLC. 1935941 1 21 theme reverse-phase 198:210 arg1 HPLC 212:215 reverse-phase HPLC 198:215 reverse-phase HPLC 198:215 Fucosyl glycoasparagines accumulating in the urine of a patient with fucosidosis were isolated using reverse-phase HPLC. 1935941 3 22 theme glycans 445:451 arg1 catabolism 407:416 the incomplete catabolism 392:416 the incomplete catabolism of N-glycosidically linked glycans 392:451 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 6 23 theme fucosyl 865:871 arg1 linkages 873:880 the fucosyl linkages 861:880 the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type 861:957 The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. 1935941 0 24 theme 1H-NMR 29:34 arg1 analysis 36:43 400-MHz 1H-NMR analysis 21:43 400-MHz 1H-NMR analysis 21:43 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 5 25 attach linked 671:676 arg2 residues 630:637 Fucose residues 623:637 Fucose residues on the peripheral branches 623:664 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 25 attach linked 671:676 arg1 residues 705:712 GlcNAc residues 698:712 GlcNAc residues (X determinant) 698:728 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 25 attach linked 671:676 arg1 determinant 717:727 X determinant 715:727 X determinant 715:727 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 25 attach linked 671:676 arg1 residues 756:763 alpha-1,2 to galactose residues 733:763 alpha-1,2 to galactose residues (H determinant) 733:779 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 25 attach linked 671:676 arg1 determinant 768:778 H determinant 766:778 H determinant 766:778 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 26 theme peripheral 646:655 arg1 branches 657:664 the peripheral branches 642:664 the peripheral branches 642:664 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 0 27 theme 400-MHz 21:27 arg1 analysis 36:43 400-MHz 1H-NMR analysis 21:43 400-MHz 1H-NMR analysis 21:43 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 4 28 link alpha-1,6-linked 558:573 arg1 residue 550:556 a fucose residue 541:556 a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine 541:620 All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. 1935941 2 29 theme spectroscopy 326:337 arg1 combination 280:290 combination 280:290 combination of methylation and 400-MHz 1H-NMR spectroscopy analyses 280:346 Structural analysis of 25 glycoasparagines was carried out by combination of methylation and 400-MHz 1H-NMR spectroscopy analyses. 1935941 5 30 theme H 766:766 arg1 residues 756:763 alpha-1,2 to galactose residues 733:763 alpha-1,2 to galactose residues (H determinant) 733:779 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 30 theme H 766:766 arg1 determinant 768:778 H determinant 766:778 H determinant 766:778 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 0 31 from fucosidosis 84:94 arg1 Characterization 0:15 Characterization 0:15 Characterization 0:15 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 0 31 from fucosidosis 84:94 arg1 analysis 36:43 400-MHz 1H-NMR analysis 21:43 400-MHz 1H-NMR analysis 21:43 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 5 32 dep residues 705:712 arg1 either 678:683 either 678:683 either 678:683 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 6 33 theme linked 912:917 arg1 glycans 919:925 N-glycosidically linked glycans 895:925 N-glycosidically linked glycans of the N-acetyllactosamine type 895:957 The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. 1935941 0 34 theme fucosyl 56:62 arg1 glycoasparagines 64:79 urinary fucosyl glycoasparagines 48:79 urinary fucosyl glycoasparagines in fucosidosis 48:94 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 4 35 theme GlcNAc 582:587 arg1 residue 591:597 the GlcNAc 1 residue 578:597 the GlcNAc 1 residue attached to asparagine 578:620 All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. 1935941 0 36 from glycoasparagines 64:79 arg1 fucosidosis 84:94 fucosidosis 84:94 fucosidosis 84:94 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 2 37 theme glycoasparagines 244:259 arg1 analysis 229:236 Structural analysis 218:236 Structural analysis of 25 glycoasparagines 218:259 Structural analysis of 25 glycoasparagines was carried out by combination of methylation and 400-MHz 1H-NMR spectroscopy analyses. 1935941 6 38 theme N-acetyllactosamine 934:952 arg1 type 954:957 the N-acetyllactosamine type 930:957 the N-acetyllactosamine type 930:957 The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. 1935941 6 39 link linked 912:917 arg1 glycans 919:925 N-glycosidically linked glycans 895:925 N-glycosidically linked glycans of the N-acetyllactosamine type 895:957 The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. 1935941 0 40 theme urinary 48:54 arg1 glycoasparagines 64:79 urinary fucosyl glycoasparagines 48:79 urinary fucosyl glycoasparagines in fucosidosis 48:94 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 5 41 theme alpha-1,2 733:741 arg1 residues 756:763 alpha-1,2 to galactose residues 733:763 alpha-1,2 to galactose residues (H determinant) 733:779 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 41 theme alpha-1,2 733:741 arg1 determinant 768:778 H determinant 766:778 H determinant 766:778 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 42 theme Fucose 623:628 arg1 residues 630:637 Fucose residues 623:637 Fucose residues on the peripheral branches 623:664 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 43 from residues 630:637 arg1 branches 657:664 the peripheral branches 642:664 the peripheral branches 642:664 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 44 theme galactose 746:754 arg1 residues 756:763 alpha-1,2 to galactose residues 733:763 alpha-1,2 to galactose residues (H determinant) 733:779 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 5 44 theme galactose 746:754 arg1 determinant 768:778 H determinant 766:778 H determinant 766:778 Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). 1935941 2 45 theme Structural 218:227 arg1 analysis 229:236 Structural analysis 218:236 Structural analysis of 25 glycoasparagines 218:259 Structural analysis of 25 glycoasparagines was carried out by combination of methylation and 400-MHz 1H-NMR spectroscopy analyses. 1935941 6 46 theme present 786:792 arg1 study 794:798 The present study 782:798 The present study 782:798 The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. 1935941 4 47 contain possess 533:539 arg1 All 505:507 All 505:507 All 505:507 All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. 1935941 4 47 contain possess 533:539 arg1 glycoasparagines 516:531 the glycoasparagines 512:531 the glycoasparagines 512:531 All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. 1935941 4 47 contain possess 533:539 arg2 residue 550:556 a fucose residue 541:556 a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine 541:620 All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. 1935941 3 48 theme different 373:381 arg1 steps 383:387 different steps 373:387 different steps in the incomplete catabolism of N-glycosidically linked glycans 373:451 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 3 48 theme different 373:381 arg1 result 461:466 the result 457:466 the result of an alpha-L-fucosidase deficiency 457:502 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 3 49 from steps 383:387 arg1 catabolism 407:416 the incomplete catabolism 392:416 the incomplete catabolism of N-glycosidically linked glycans 392:451 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 3 50 link linked 438:443 arg1 glycans 445:451 N-glycosidically linked glycans 421:451 N-glycosidically linked glycans 421:451 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 1 51 theme patient 153:159 arg1 urine 142:146 the urine 138:146 the urine of a patient with fucosidosis 138:176 Fucosyl glycoasparagines accumulating in the urine of a patient with fucosidosis were isolated using reverse-phase HPLC. 1935941 0 52 theme glycoasparagines 64:79 arg1 Characterization 0:15 Characterization 0:15 Characterization 0:15 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 0 52 theme glycoasparagines 64:79 arg1 analysis 36:43 400-MHz 1H-NMR analysis 21:43 400-MHz 1H-NMR analysis 21:43 Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. 1935941 4 53 theme alpha-1,6-linked 558:573 arg1 residue 550:556 a fucose residue 541:556 a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine 541:620 All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. 1935941 3 54 theme N-glycosidically 421:436 arg1 glycans 445:451 N-glycosidically linked glycans 421:451 N-glycosidically linked glycans 421:451 The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. 1935941 2 55 dep methylation 295:305 arg1 analyses 339:346 analyses 339:346 analyses 339:346 Structural analysis of 25 glycoasparagines was carried out by combination of methylation and 400-MHz 1H-NMR spectroscopy analyses. 7737204 6 0 theme N-glycolylneuraminic 1219:1238 arg1 acid 1240:1243 N-glycolylneuraminic acid 1219:1243 N-glycolylneuraminic acid (2%) 1219:1248 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 0 theme N-glycolylneuraminic 1219:1238 arg1 % 1247:1247 2% 1246:1247 2% 1246:1247 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 0 theme N-glycolylneuraminic 1219:1238 arg1 types 1128:1132 Three different types 1112:1132 Three different types of alpha 2-3-linked sialic acids 1112:1165 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 8 1 from present 1547:1553 arg1 oligosaccharides 1624:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 2 2 theme amidase 407:413 arg1 F 415:415 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 357:415 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 357:415 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 8 3 located located 1470:1476 arg2 units 1445:1449 One or two extra N-acetyllactosamine units 1408:1449 One or two extra N-acetyllactosamine units 1408:1449 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 8 3 located located 1470:1476 arg1 branches 1485:1492 the branches 1481:1492 the branches attached to the alpha 1-6-linked Man residue 1481:1537 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 9 4 theme same 1814:1817 arg1 conditions 1819:1828 the same conditions 1810:1828 the same conditions 1810:1828 Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). 7737204 10 5 theme antennary 1953:1961 arg1 oligosaccharides 1963:1978 these tri'antennary oligosaccharides 1943:1978 these tri'antennary oligosaccharides 1943:1978 Using endo-beta-galactosidase from Escherichia freundii, these tri'antennary oligosaccharides could be digested more extensively (> 75%). 7737204 11 6 theme alkaline 2098:2105 arg1 borohydride 2107:2117 alkaline borohydride 2098:2117 alkaline borohydride treatment 2098:2127 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 10 7 dep digested 1989:1996 arg1 % 2020:2020 > 75% 2016:2020 > 75% 2016:2020 Using endo-beta-galactosidase from Escherichia freundii, these tri'antennary oligosaccharides could be digested more extensively (> 75%). 7737204 11 8 theme Mono 2155:2158 arg1 Q 2160:2160 Mono Q 2155:2160 Mono Q 2155:2160 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 9 9 theme antennary 1835:1843 arg1 oligosaccharides 1845:1860 tri' antennary oligosaccharides 1830:1860 tri' antennary oligosaccharides 1830:1860 Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). 7737204 12 10 theme 2-3Gal 2279:2284 arg1 beta 2286:2289 Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3 2224:2293 beta 2286:2289 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 1 11 theme dimeric 196:202 arg1 units 224:228 dimeric N-acetyllactosamine units 196:228 dimeric N-acetyllactosamine units 196:228 Sialylation patterns and branch location of dimeric N-acetyllactosamine units. 7737204 6 12 theme different 1118:1126 arg1 acid 1240:1243 N-glycolylneuraminic acid 1219:1243 N-glycolylneuraminic acid (2%) 1219:1248 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 12 theme different 1118:1126 arg1 acid 1207:1210 N-acetylneuraminic acid 1188:1210 N-acetylneuraminic acid (95%) 1188:1216 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 12 theme different 1118:1126 arg1 acid 1284:1287 N-acetyl-9-O-acetylneuraminic acid 1254:1287 N-acetyl-9-O-acetylneuraminic acid (3%) 1254:1292 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 12 theme different 1118:1126 arg1 types 1128:1132 Three different types 1112:1132 Three different types of alpha 2-3-linked sialic acids 1112:1165 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 11 13 theme borohydride 2107:2117 arg1 treatment 2119:2127 alkaline borohydride treatment 2098:2127 alkaline borohydride treatment 2098:2127 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 12 14 theme 2-3Gal 2237:2242 arg1 1-3GalNAc-ol 2249:2260 Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3 2224:2293 1-3GalNAc-ol 2249:2260 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 12 14 theme 2-3Gal 2237:2242 arg1 alpha 2302:2306 Neu5Ac alpha 2-6 2295:2310 Neu5Ac alpha 2-6 2295:2310 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 0 15 theme Chinese 123:129 arg1 cells 145:149 Chinese hamster ovary cells 123:149 Chinese hamster ovary cells 123:149 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 6 16 link 2-3-linked 1143:1152 arg1 acids 1161:1165 alpha 2-3-linked sialic acids 1137:1165 alpha 2-3-linked sialic acids 1137:1165 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 1 17 theme units 224:228 arg1 patterns 164:171 Sialylation patterns 152:171 Sialylation patterns 152:171 Sialylation patterns and branch location of dimeric N-acetyllactosamine units. 7737204 1 17 theme units 224:228 arg1 location 184:191 branch location 177:191 branch location 177:191 Sialylation patterns and branch location of dimeric N-acetyllactosamine units. 7737204 2 18 theme CarboPac 614:621 arg1 PA1 623:625 CarboPac PA1 614:625 CarboPac PA1 614:625 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 0 19 theme ovary 139:143 arg1 cells 145:149 Chinese hamster ovary cells 123:149 Chinese hamster ovary cells 123:149 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 7 20 located observed 1398:1405 arg2 distribution 1344:1355 a non-random distribution 1331:1355 a non-random distribution of the sialic acids over the branches 1331:1393 In the case of partial sialylation, a non-random distribution of the sialic acids over the branches is observed. 7737204 7 20 located observed 1398:1405 arg1 case 1302:1305 the case 1298:1305 the case of partial sialylation 1298:1328 In the case of partial sialylation, a non-random distribution of the sialic acids over the branches is observed. 7737204 3 21 theme one-dimensional 686:700 arg1 spectroscopy 737:748 one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy 686:748 one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy 686:748 The purified sialylated oligosaccharides were analyzed by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. 7737204 8 22 gly sialylated 1582:1591 arg1 oligosaccharides 1624:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 9 23 with oligosaccharides 1657:1672 arg1 repeats 1699:1705 N-acetyllactosamine repeats 1679:1705 N-acetyllactosamine repeats 1679:1705 Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). 7737204 2 24 theme N-linked 235:242 arg1 chains 257:262 The N-linked carbohydrate chains 231:262 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells 231:321 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 12 25 theme Neu5Ac 2224:2229 arg1 1-3GalNAc-ol 2249:2260 Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3 2224:2293 1-3GalNAc-ol 2249:2260 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 12 25 theme Neu5Ac 2224:2229 arg1 alpha 2302:2306 Neu5Ac alpha 2-6 2295:2310 Neu5Ac alpha 2-6 2295:2310 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 3 26 theme 1H-NMR 730:735 arg1 spectroscopy 737:748 one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy 686:748 one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy 686:748 The purified sialylated oligosaccharides were analyzed by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. 7737204 8 27 located present 1547:1553 arg2 units 1445:1449 One or two extra N-acetyllactosamine units 1408:1449 One or two extra N-acetyllactosamine units 1408:1449 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 8 27 located present 1547:1553 arg1 oligosaccharides 1624:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 7 28 theme non-random 1333:1342 arg1 distribution 1344:1355 a non-random distribution 1331:1355 a non-random distribution of the sialic acids over the branches 1331:1393 In the case of partial sialylation, a non-random distribution of the sialic acids over the branches is observed. 7737204 3 29 theme two-dimensional 706:720 arg1 spectroscopy 737:748 one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy 686:748 one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy 686:748 The purified sialylated oligosaccharides were analyzed by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. 7737204 1 30 theme Sialylation 152:162 arg1 patterns 164:171 Sialylation patterns 152:171 Sialylation patterns 152:171 Sialylation patterns and branch location of dimeric N-acetyllactosamine units. 7737204 6 31 theme acids 1161:1165 arg1 acid 1240:1243 N-glycolylneuraminic acid 1219:1243 N-glycolylneuraminic acid (2%) 1219:1248 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 31 theme acids 1161:1165 arg1 acid 1207:1210 N-acetylneuraminic acid 1188:1210 N-acetylneuraminic acid (95%) 1188:1216 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 31 theme acids 1161:1165 arg1 acid 1284:1287 N-acetyl-9-O-acetylneuraminic acid 1254:1287 N-acetyl-9-O-acetylneuraminic acid (3%) 1254:1292 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 31 theme acids 1161:1165 arg1 types 1128:1132 Three different types 1112:1132 Three different types of alpha 2-3-linked sialic acids 1112:1165 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 8 32 theme di- 1593:1595 arg1 oligosaccharides 1624:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 8 33 theme N-acetyllactosamine 1425:1443 arg1 units 1445:1449 One or two extra N-acetyllactosamine units 1408:1449 One or two extra N-acetyllactosamine units 1408:1449 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 9 34 dep reacted 1869:1875 arg1 % 1882:1882 < 15% 1878:1882 < 15% 1878:1882 Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). 7737204 2 35 from chromatography 596:609 arg1 PA1 623:625 CarboPac PA1 614:625 CarboPac PA1 614:625 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 6 36 theme 2-3-linked 1143:1152 arg1 acids 1161:1165 alpha 2-3-linked sialic acids 1137:1165 alpha 2-3-linked sialic acids 1137:1165 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 8 37 theme tri'- 1598:1602 arg1 oligosaccharides 1624:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 4 38 theme products 908:915 arg1 analysis 881:888 1H-NMR analysis 874:888 1H-NMR analysis of the incubation products 874:915 When necessary, oligosaccharides were treated with endo-beta-galactosidase (and N-acetyl-beta-glucosaminidase) followed by 1H-NMR analysis of the incubation products, to obtain additional structural information. 7737204 0 39 theme human 89:93 arg1 erythropoietin 95:108 recombinant human erythropoietin 77:108 recombinant human erythropoietin 77:108 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 0 40 gly sialylated 27:36 arg1 N- 38:39 the sialylated N- 23:39 the sialylated N- 23:39 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 8 41 link 1-6-linked 1516:1525 arg1 residue 1531:1537 the alpha 1-6-linked Man residue 1506:1537 the alpha 1-6-linked Man residue 1506:1537 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 2 42 theme high-pH 573:579 arg1 chromatography 596:609 high-pH anion-exchange chromatography 573:609 high-pH anion-exchange chromatography on CarboPac PA1 573:625 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 9 43 theme N-acetyllactosamine 1679:1697 arg1 repeats 1699:1705 N-acetyllactosamine repeats 1679:1705 N-acetyllactosamine repeats 1679:1705 Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). 7737204 6 44 dep present 1171:1177 arg1 % 1247:1247 2% 1246:1247 2% 1246:1247 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 44 dep present 1171:1177 arg1 % 1291:1291 3% 1290:1291 3% 1290:1291 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 44 dep present 1171:1177 arg1 acid 1207:1210 N-acetylneuraminic acid 1188:1210 N-acetylneuraminic acid (95%) 1188:1216 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 44 dep present 1171:1177 arg1 types 1128:1132 Three different types 1112:1132 Three different types of alpha 2-3-linked sialic acids 1112:1165 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 44 dep present 1171:1177 arg1 acid 1240:1243 N-glycolylneuraminic acid 1219:1243 N-glycolylneuraminic acid (2%) 1219:1248 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 44 dep present 1171:1177 arg1 acid 1284:1287 N-acetyl-9-O-acetylneuraminic acid 1254:1287 N-acetyl-9-O-acetylneuraminic acid (3%) 1254:1292 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 44 dep present 1171:1177 arg1 % 1215:1215 95% 1213:1215 95% 1213:1215 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 0 45 theme chains 67:72 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin 0:108 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 11 46 theme carbohydrate 2037:2048 arg1 chains 2050:2055 The O-linked carbohydrate chains 2024:2055 The O-linked carbohydrate chains 2024:2055 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 0 47 theme Structural 0:9 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin 0:108 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 6 48 theme N-acetylneuraminic 1188:1205 arg1 acid 1207:1210 N-acetylneuraminic acid 1188:1210 N-acetylneuraminic acid (95%) 1188:1216 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 48 theme N-acetylneuraminic 1188:1205 arg1 % 1215:1215 95% 1213:1215 95% 1213:1215 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 48 theme N-acetylneuraminic 1188:1205 arg1 types 1128:1132 Three different types 1112:1132 Three different types of alpha 2-3-linked sialic acids 1112:1165 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 2 49 theme gel-permeation 465:478 arg1 chromatography 480:493 gel-permeation chromatography 465:493 gel-permeation chromatography 465:493 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 1 50 theme branch 177:182 arg1 location 184:191 branch location 177:191 branch location 177:191 Sialylation patterns and branch location of dimeric N-acetyllactosamine units. 7737204 0 51 theme sialylated 27:36 arg1 N- 38:39 the sialylated N- 23:39 the sialylated N- 23:39 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 0 52 theme carbohydrate 54:65 arg1 chains 67:72 O-linked carbohydrate chains 45:72 O-linked carbohydrate chains 45:72 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 8 53 theme alpha 1510:1514 arg1 residue 1531:1537 the alpha 1-6-linked Man residue 1506:1537 the alpha 1-6-linked Man residue 1506:1537 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 2 54 theme asparagine 396:405 arg1 F 415:415 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 357:415 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 357:415 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 11 55 from HPLC 2166:2169 arg1 Lichrosorb-NH2 2174:2187 Lichrosorb-NH2 2174:2187 Lichrosorb-NH2 2174:2187 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 2 56 theme recombinant 267:277 arg1 erythropoietin 285:298 recombinant human erythropoietin 267:298 recombinant human erythropoietin expressed in CHO cells 267:321 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 4 57 theme additional 928:937 arg1 information 950:960 additional structural information 928:960 additional structural information 928:960 When necessary, oligosaccharides were treated with endo-beta-galactosidase (and N-acetyl-beta-glucosaminidase) followed by 1H-NMR analysis of the incubation products, to obtain additional structural information. 7737204 2 58 theme N-acetyl-beta-glucosaminyl 369:394 arg1 F 415:415 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 357:415 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 357:415 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 12 59 theme Neu5Ac 2295:2300 arg1 1-3GalNAc-ol 2249:2260 Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3 2224:2293 1-3GalNAc-ol 2249:2260 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 12 59 theme Neu5Ac 2295:2300 arg1 alpha 2302:2306 Neu5Ac alpha 2-6 2295:2310 Neu5Ac alpha 2-6 2295:2310 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 7 60 theme sialic 1364:1369 arg1 acids 1371:1375 the sialic acids 1360:1375 the sialic acids 1360:1375 In the case of partial sialylation, a non-random distribution of the sialic acids over the branches is observed. 7737204 7 61 theme sialylation 1318:1328 arg1 case 1302:1305 the case 1298:1305 the case of partial sialylation 1298:1328 In the case of partial sialylation, a non-random distribution of the sialic acids over the branches is observed. 7737204 11 62 gly O-glycoprotein 2080:2093 arg1 O-glycoprotein 2080:2093 the O-glycoprotein 2076:2093 the O-glycoprotein 2076:2093 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 11 63 from Q 2160:2160 arg1 Lichrosorb-NH2 2174:2187 Lichrosorb-NH2 2174:2187 Lichrosorb-NH2 2174:2187 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 8 64 from located 1470:1476 arg1 branches 1485:1492 the branches 1481:1492 the branches attached to the alpha 1-6-linked Man residue 1481:1537 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 3 65 theme sialylated 641:650 arg1 oligosaccharides 652:667 The purified sialylated oligosaccharides 628:667 The purified sialylated oligosaccharides 628:667 The purified sialylated oligosaccharides were analyzed by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. 7737204 5 66 dep Di- 963:965 arg1 oligosaccharides 1024:1039 N-acetyllactosamine-type oligosaccharides 999:1039 N-acetyllactosamine-type oligosaccharides 999:1039 Di-, tri-, tri'- and tetraantennary N-acetyllactosamine-type oligosaccharides occur which can be completely (major) or partially (minor) sialylated. 7737204 9 67 theme Bacteroides 1774:1784 arg1 fragilis 1786:1793 Bacteroides fragilis 1774:1793 Bacteroides fragilis 1774:1793 Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). 7737204 2 68 theme CHO 313:315 arg1 cells 317:321 CHO cells 313:321 CHO cells 313:321 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 5 69 theme N-acetyllactosamine-type 999:1022 arg1 oligosaccharides 1024:1039 N-acetyllactosamine-type oligosaccharides 999:1039 N-acetyllactosamine-type oligosaccharides 999:1039 Di-, tri-, tri'- and tetraantennary N-acetyllactosamine-type oligosaccharides occur which can be completely (major) or partially (minor) sialylated. 7737204 0 70 link O-linked 45:52 arg1 chains 67:72 O-linked carbohydrate chains 45:72 O-linked carbohydrate chains 45:72 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 2 71 theme peptide-N4- 357:367 arg1 F 415:415 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 357:415 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 357:415 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 12 72 theme alpha 2273:2277 arg1 beta 2286:2289 Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3 2224:2293 beta 2286:2289 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 0 73 theme hamster 131:137 arg1 cells 145:149 Chinese hamster ovary cells 123:149 Chinese hamster ovary cells 123:149 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 1 74 theme N-acetyllactosamine 204:222 arg1 units 224:228 dimeric N-acetyllactosamine units 196:228 dimeric N-acetyllactosamine units 196:228 Sialylation patterns and branch location of dimeric N-acetyllactosamine units. 7737204 8 75 from oligosaccharides 1624:1639 arg1 present 1547:1553 present 1547:1553 present 1547:1553 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 6 76 theme N-acetyl-9-O-acetylneuraminic 1254:1282 arg1 acid 1284:1287 N-acetyl-9-O-acetylneuraminic acid 1254:1287 N-acetyl-9-O-acetylneuraminic acid (3%) 1254:1292 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 76 theme N-acetyl-9-O-acetylneuraminic 1254:1282 arg1 % 1291:1291 3% 1290:1291 3% 1290:1291 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 6 76 theme N-acetyl-9-O-acetylneuraminic 1254:1282 arg1 types 1128:1132 Three different types 1112:1132 Three different types of alpha 2-3-linked sialic acids 1112:1165 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 12 77 theme alpha 2231:2235 arg1 1-3GalNAc-ol 2249:2260 Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3 2224:2293 1-3GalNAc-ol 2249:2260 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 12 77 theme alpha 2231:2235 arg1 alpha 2302:2306 Neu5Ac alpha 2-6 2295:2310 Neu5Ac alpha 2-6 2295:2310 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 9 78 theme < 1878:1878 arg1 % 1882:1882 < 15% 1878:1882 < 15% 1878:1882 Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). 7737204 2 79 from Lichrosorb-NH2 554:567 arg1 PA1 623:625 CarboPac PA1 614:625 CarboPac PA1 614:625 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 12 80 theme beta 2244:2247 arg1 1-3GalNAc-ol 2249:2260 Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3 2224:2293 1-3GalNAc-ol 2249:2260 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 12 80 theme beta 2244:2247 arg1 alpha 2302:2306 Neu5Ac alpha 2-6 2295:2310 Neu5Ac alpha 2-6 2295:2310 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 11 81 attach released 2062:2069 arg1 O-glycoprotein 2080:2093 the O-glycoprotein 2076:2093 the O-glycoprotein 2076:2093 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 11 81 attach released 2062:2069 arg2 chains 2050:2055 The O-linked carbohydrate chains 2024:2055 The O-linked carbohydrate chains 2024:2055 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 2 82 theme carbohydrate 244:255 arg1 chains 257:262 The N-linked carbohydrate chains 231:262 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells 231:321 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 3 83 gly sialylated 641:650 arg1 oligosaccharides 652:667 The purified sialylated oligosaccharides 628:667 The purified sialylated oligosaccharides 628:667 The purified sialylated oligosaccharides were analyzed by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. 7737204 8 84 theme Man 1527:1529 arg1 residue 1531:1537 the alpha 1-6-linked Man residue 1506:1537 the alpha 1-6-linked Man residue 1506:1537 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 3 85 theme 500-MHz 722:728 arg1 spectroscopy 737:748 one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy 686:748 one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy 686:748 The purified sialylated oligosaccharides were analyzed by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. 7737204 8 86 theme sialylated 1582:1591 arg1 oligosaccharides 1624:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 5 87 dep or 1079:1080 arg1 minor 1093:1097 minor 1093:1097 minor 1093:1097 Di-, tri-, tri'- and tetraantennary N-acetyllactosamine-type oligosaccharides occur which can be completely (major) or partially (minor) sialylated. 7737204 5 87 dep or 1079:1080 arg1 major 1072:1076 major 1072:1076 major 1072:1076 Di-, tri-, tri'- and tetraantennary N-acetyllactosamine-type oligosaccharides occur which can be completely (major) or partially (minor) sialylated. 7737204 2 88 link N-linked 235:242 arg1 chains 257:262 The N-linked carbohydrate chains 231:262 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells 231:321 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 5 89 gly sialylated 1100:1109 arg1 which 1047:1051 which 1047:1051 which 1047:1051 Di-, tri-, tri'- and tetraantennary N-acetyllactosamine-type oligosaccharides occur which can be completely (major) or partially (minor) sialylated. 7737204 2 90 theme human 279:283 arg1 erythropoietin 285:298 recombinant human erythropoietin 267:298 recombinant human erythropoietin expressed in CHO cells 267:321 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 12 91 dep GalNAc-ol 2312:2320 arg1 beta 2286:2289 Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3 2224:2293 beta 2286:2289 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 12 91 dep GalNAc-ol 2312:2320 arg1 1-3GalNAc-ol 2249:2260 Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3 2224:2293 1-3GalNAc-ol 2249:2260 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 12 91 dep GalNAc-ol 2312:2320 arg1 alpha 2302:2306 Neu5Ac alpha 2-6 2295:2310 Neu5Ac alpha 2-6 2295:2310 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 9 92 dep digested 1716:1723 arg1 whereas 1796:1802 whereas 1796:1802 whereas 1796:1802 Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). 7737204 7 93 theme partial 1310:1316 arg1 sialylation 1318:1328 partial sialylation 1310:1328 partial sialylation 1310:1328 In the case of partial sialylation, a non-random distribution of the sialic acids over the branches is observed. 7737204 0 94 theme recombinant 77:87 arg1 erythropoietin 95:108 recombinant human erythropoietin 77:108 recombinant human erythropoietin 77:108 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 6 95 theme sialic 1154:1159 arg1 acids 1161:1165 alpha 2-3-linked sialic acids 1137:1165 alpha 2-3-linked sialic acids 1137:1165 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 8 96 theme extra 1419:1423 arg1 units 1445:1449 One or two extra N-acetyllactosamine units 1408:1449 One or two extra N-acetyllactosamine units 1408:1449 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 0 97 theme erythropoietin 95:108 arg1 N- 38:39 the sialylated N- 23:39 the sialylated N- 23:39 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 0 97 theme erythropoietin 95:108 arg1 chains 67:72 O-linked carbohydrate chains 45:72 O-linked carbohydrate chains 45:72 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 9 98 theme Tetraantennary 1642:1655 arg1 oligosaccharides 1657:1672 Tetraantennary oligosaccharides 1642:1672 Tetraantennary oligosaccharides with N-acetyllactosamine repeats 1642:1705 Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). 7737204 3 99 theme purified 632:639 arg1 oligosaccharides 652:667 The purified sialylated oligosaccharides 628:667 The purified sialylated oligosaccharides 628:667 The purified sialylated oligosaccharides were analyzed by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. 7737204 6 100 theme alpha 1137:1141 arg1 acids 1161:1165 alpha 2-3-linked sialic acids 1137:1165 alpha 2-3-linked sialic acids 1137:1165 Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). 7737204 2 101 theme anion-exchange 581:594 arg1 chromatography 596:609 high-pH anion-exchange chromatography 573:609 high-pH anion-exchange chromatography on CarboPac PA1 573:625 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 8 102 theme tetraantennary 1609:1622 arg1 oligosaccharides 1624:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 4 103 theme incubation 897:906 arg1 products 908:915 the incubation products 893:915 the incubation products 893:915 When necessary, oligosaccharides were treated with endo-beta-galactosidase (and N-acetyl-beta-glucosaminidase) followed by 1H-NMR analysis of the incubation products, to obtain additional structural information. 7737204 2 104 from Q 543:543 arg1 Lichrosorb-NH2 554:567 Lichrosorb-NH2 554:567 Lichrosorb-NH2 554:567 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 2 104 from Q 543:543 arg1 chromatography 596:609 high-pH anion-exchange chromatography 573:609 high-pH anion-exchange chromatography on CarboPac PA1 573:625 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 2 105 gly O-glycoprotein 447:460 arg1 O-glycoprotein 447:460 the remaining O-glycoprotein 433:460 the remaining O-glycoprotein 433:460 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 2 106 theme remaining 437:445 arg1 O-glycoprotein 447:460 the remaining O-glycoprotein 433:460 the remaining O-glycoprotein 433:460 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 8 107 attach attached 1494:1501 arg2 branches 1485:1492 the branches 1481:1492 the branches attached to the alpha 1-6-linked Man residue 1481:1537 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 8 107 attach attached 1494:1501 arg1 residue 1531:1537 the alpha 1-6-linked Man residue 1506:1537 the alpha 1-6-linked Man residue 1506:1537 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 9 108 from fragilis 1786:1793 arg1 endo-beta-galactosidase 1745:1767 endo-beta-galactosidase 1745:1767 endo-beta-galactosidase from Bacteroides fragilis 1745:1793 Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). 7737204 4 109 theme 1H-NMR 874:879 arg1 analysis 881:888 1H-NMR analysis 874:888 1H-NMR analysis of the incubation products 874:915 When necessary, oligosaccharides were treated with endo-beta-galactosidase (and N-acetyl-beta-glucosaminidase) followed by 1H-NMR analysis of the incubation products, to obtain additional structural information. 7737204 0 110 theme N- 38:39 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin 0:108 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 2 111 theme Mono 538:541 arg1 HPLC 546:549 HPLC 546:549 HPLC 546:549 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 2 111 theme Mono 538:541 arg1 Q 543:543 Mono Q 538:543 Mono Q 538:543 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 10 112 theme > 2016:2016 arg1 % 2020:2020 > 75% 2016:2020 > 75% 2016:2020 Using endo-beta-galactosidase from Escherichia freundii, these tri'antennary oligosaccharides could be digested more extensively (> 75%). 7737204 2 113 theme erythropoietin 285:298 arg1 chains 257:262 The N-linked carbohydrate chains 231:262 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells 231:321 The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. 7737204 0 114 theme O-linked 45:52 arg1 chains 67:72 O-linked carbohydrate chains 45:72 O-linked carbohydrate chains 45:72 Structural analysis of the sialylated N- and O-linked carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. 7737204 11 115 link O-linked 2028:2035 arg1 chains 2050:2055 The O-linked carbohydrate chains 2024:2055 The O-linked carbohydrate chains 2024:2055 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 4 116 dep treated 789:795 arg1 followed 862:869 followed 862:869 followed 862:869 When necessary, oligosaccharides were treated with endo-beta-galactosidase (and N-acetyl-beta-glucosaminidase) followed by 1H-NMR analysis of the incubation products, to obtain additional structural information. 7737204 7 117 theme acids 1371:1375 arg1 distribution 1344:1355 a non-random distribution 1331:1355 a non-random distribution of the sialic acids over the branches 1331:1393 In the case of partial sialylation, a non-random distribution of the sialic acids over the branches is observed. 7737204 8 118 theme 1-6-linked 1516:1525 arg1 residue 1531:1537 the alpha 1-6-linked Man residue 1506:1537 the alpha 1-6-linked Man residue 1506:1537 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 8 119 attach present 1547:1553 arg2 units 1445:1449 One or two extra N-acetyllactosamine units 1408:1449 One or two extra N-acetyllactosamine units 1408:1449 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 8 119 attach present 1547:1553 arg1 oligosaccharides 1624:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides 1558:1639 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 7737204 12 120 theme Neu5Ac 2266:2271 arg1 beta 2286:2289 Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3 2224:2293 beta 2286:2289 Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol. 7737204 4 121 theme structural 939:948 arg1 information 950:960 additional structural information 928:960 additional structural information 928:960 When necessary, oligosaccharides were treated with endo-beta-galactosidase (and N-acetyl-beta-glucosaminidase) followed by 1H-NMR analysis of the incubation products, to obtain additional structural information. 7737204 11 122 theme O-linked 2028:2035 arg1 chains 2050:2055 The O-linked carbohydrate chains 2024:2055 The O-linked carbohydrate chains 2024:2055 The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. 7737204 8 123 from branches 1485:1492 arg1 located 1470:1476 located 1470:1476 located 1470:1476 One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. 1425697 5 0 contain contained 850:858 arg1 some 830:833 some 830:833 some 830:833 In total, more than 150 carbohydrate-containing fractions were obtained, some of which still contained mixtures of oligosaccharides. 1425697 5 0 contain contained 850:858 arg2 mixtures 860:867 mixtures 860:867 mixtures of oligosaccharides 860:887 In total, more than 150 carbohydrate-containing fractions were obtained, some of which still contained mixtures of oligosaccharides. 1425697 5 0 contain contained 850:858 arg1 which 838:842 which 838:842 which 838:842 In total, more than 150 carbohydrate-containing fractions were obtained, some of which still contained mixtures of oligosaccharides. 1425697 7 1 theme terminal 1237:1244 arg1 elements 1257:1264 the following terminal structural elements 1223:1264 the following terminal structural elements 1223:1264 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 7 2 theme compounds 1066:1074 arg1 types 1057:1061 The types 1053:1061 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1053:1285 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 0 3 theme male 78:81 arg1 glycoprotein 58:69 human Tamm-Horsfall glycoprotein 38:69 human Tamm-Horsfall glycoprotein of one male 38:81 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. 1425697 6 4 theme 1H-NMR 1010:1015 arg1 spectroscopy 1017:1028 one- and two-dimensional 1H-NMR spectroscopy 985:1028 one- and two-dimensional 1H-NMR spectroscopy 985:1028 The primary structure of 30 N-glycans, including 10 novel oligosaccharides, were determined by one- and two-dimensional 1H-NMR spectroscopy at 500 MHz or 600 MHz. 1425697 3 5 theme Asn-linked 255:264 arg1 chains 279:284 The Asn-linked carbohydrate chains 251:284 The Asn-linked carbohydrate chains 251:284 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 6 6 theme novel 942:946 arg1 oligosaccharides 948:963 10 novel oligosaccharides 939:963 10 novel oligosaccharides 939:963 The primary structure of 30 N-glycans, including 10 novel oligosaccharides, were determined by one- and two-dimensional 1H-NMR spectroscopy at 500 MHz or 600 MHz. 1425697 3 7 theme remaining 399:407 arg1 protein 409:415 the remaining protein 395:415 the remaining protein 395:415 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 6 8 theme two-dimensional 994:1008 arg1 spectroscopy 1017:1028 one- and two-dimensional 1H-NMR spectroscopy 985:1028 one- and two-dimensional 1H-NMR spectroscopy 985:1028 The primary structure of 30 N-glycans, including 10 novel oligosaccharides, were determined by one- and two-dimensional 1H-NMR spectroscopy at 500 MHz or 600 MHz. 1425697 7 9 contain possessing 1212:1221 arg2 elements 1257:1264 the following terminal structural elements 1223:1264 the following terminal structural elements 1223:1264 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 7 9 contain possessing 1212:1221 arg1 chains 1204:1209 non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains 1098:1209 non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains 1098:1209 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 7 10 theme following 1227:1235 arg1 elements 1257:1264 the following terminal structural elements 1223:1264 the following terminal structural elements 1223:1264 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 0 11 link Asn-linked 4:13 arg1 chains 28:33 The Asn-linked carbohydrate chains 0:33 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male 0:81 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. 1425697 4 12 theme amine-adsorption 656:671 arg1 HPLC 673:676 amine-adsorption HPLC 656:676 amine-adsorption HPLC on Lichrospher-NH2 656:695 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 12 theme amine-adsorption 656:671 arg1 techniques 600:609 three liquid-chromatographic techniques 571:609 three liquid-chromatographic techniques 571:609 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 2 13 theme Tamm-Horsfall 178:190 arg1 glycoprotein 192:203 Human Tamm-Horsfall glycoprotein 172:203 Human Tamm-Horsfall glycoprotein 172:203 Human Tamm-Horsfall glycoprotein has been purified from the urine of one male. 1425697 4 14 theme high-pH 702:708 arg1 chromatography 725:738 high-pH anion-exchange chromatography 702:738 high-pH anion-exchange chromatography on CarboPac PA1 702:754 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 14 theme high-pH 702:708 arg1 techniques 600:609 three liquid-chromatographic techniques 571:609 three liquid-chromatographic techniques 571:609 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 2 15 gly glycoprotein 192:203 arg1 glycoprotein 192:203 Human Tamm-Horsfall glycoprotein 172:203 Human Tamm-Horsfall glycoprotein 172:203 Human Tamm-Horsfall glycoprotein has been purified from the urine of one male. 1425697 2 16 theme Human 172:176 arg1 glycoprotein 192:203 Human Tamm-Horsfall glycoprotein 172:203 Human Tamm-Horsfall glycoprotein 172:203 Human Tamm-Horsfall glycoprotein has been purified from the urine of one male. 1425697 4 17 theme CarboPac 743:750 arg1 PA1 752:754 CarboPac PA1 743:754 CarboPac PA1 743:754 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 0 18 theme Asn-linked 4:13 arg1 chains 28:33 The Asn-linked carbohydrate chains 0:33 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male 0:81 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. 1425697 3 19 theme carbohydrate 266:277 arg1 chains 279:284 The Asn-linked carbohydrate chains 251:284 The Asn-linked carbohydrate chains 251:284 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 1 20 theme Novel 84:88 arg1 chains 164:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains. 1425697 4 21 theme chains 531:536 arg1 Fractionation 468:480 Fractionation 468:480 Fractionation of the intact (sulfated) sialylated carbohydrate chains 468:536 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 22 from FPLC 635:638 arg1 PA1 752:754 CarboPac PA1 743:754 CarboPac PA1 743:754 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 22 from FPLC 635:638 arg1 Q-Sepharose 643:653 Q-Sepharose 643:653 Q-Sepharose 643:653 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 22 from FPLC 635:638 arg1 Lichrospher-NH2 681:695 Lichrospher-NH2 681:695 Lichrospher-NH2 681:695 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 23 theme anion-exchange 620:633 arg1 FPLC 635:638 anion-exchange FPLC 620:638 anion-exchange FPLC on Q-Sepharose 620:653 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 23 theme anion-exchange 620:633 arg1 techniques 600:609 three liquid-chromatographic techniques 571:609 three liquid-chromatographic techniques 571:609 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 6 24 theme N-glycans 918:926 arg1 structure 902:910 The primary structure 890:910 The primary structure 890:910 The primary structure of 30 N-glycans, including 10 novel oligosaccharides, were determined by one- and two-dimensional 1H-NMR spectroscopy at 500 MHz or 600 MHz. 1425697 1 25 theme sulfated 90:97 arg1 chains 164:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains. 1425697 4 26 from HPLC 673:676 arg1 PA1 752:754 CarboPac PA1 743:754 CarboPac PA1 743:754 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 26 from HPLC 673:676 arg1 Q-Sepharose 643:653 Q-Sepharose 643:653 Q-Sepharose 643:653 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 26 from HPLC 673:676 arg1 Lichrospher-NH2 681:695 Lichrospher-NH2 681:695 Lichrospher-NH2 681:695 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 7 27 theme structural 1246:1255 arg1 elements 1257:1264 the following terminal structural elements 1223:1264 the following terminal structural elements 1223:1264 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 3 28 theme peptide-N4- 315:325 arg1 F 373:373 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 315:373 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 315:373 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 6 29 theme primary 894:900 arg1 structure 902:910 The primary structure 890:910 The primary structure 890:910 The primary structure of 30 N-glycans, including 10 novel oligosaccharides, were determined by one- and two-dimensional 1H-NMR spectroscopy at 500 MHz or 600 MHz. 1425697 4 30 from chromatography 725:738 arg1 PA1 752:754 CarboPac PA1 743:754 CarboPac PA1 743:754 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 30 from chromatography 725:738 arg1 Q-Sepharose 643:653 Q-Sepharose 643:653 Q-Sepharose 643:653 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 30 from chromatography 725:738 arg1 Lichrospher-NH2 681:695 Lichrospher-NH2 681:695 Lichrospher-NH2 681:695 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 31 theme anion-exchange 710:723 arg1 chromatography 725:738 high-pH anion-exchange chromatography 702:738 high-pH anion-exchange chromatography on CarboPac PA1 702:754 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 31 theme anion-exchange 710:723 arg1 techniques 600:609 three liquid-chromatographic techniques 571:609 three liquid-chromatographic techniques 571:609 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 0 32 theme carbohydrate 15:26 arg1 chains 28:33 The Asn-linked carbohydrate chains 0:33 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male 0:81 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. 1425697 5 33 theme carbohydrate-containing 781:803 arg1 fractions 805:813 more than 150 carbohydrate-containing fractions 767:813 more than 150 carbohydrate-containing fractions 767:813 In total, more than 150 carbohydrate-containing fractions were obtained, some of which still contained mixtures of oligosaccharides. 1425697 1 34 theme novel 103:107 arg1 chains 164:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains. 1425697 3 35 theme gel-permeation 420:433 arg1 chromatography 435:448 gel-permeation chromatography 420:448 gel-permeation chromatography on Bio-Gel P-100 420:465 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 0 36 theme human 38:42 arg1 glycoprotein 58:69 human Tamm-Horsfall glycoprotein 38:69 human Tamm-Horsfall glycoprotein of one male 38:81 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. 1425697 7 37 dep non-fucosylated 1098:1112 arg1 tetrasialylated 1159:1173 tetrasialylated 1159:1173 tetrasialylated 1159:1173 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 7 37 dep non-fucosylated 1098:1112 arg1 monosialylated 1115:1128 monosialylated 1115:1128 monosialylated 1115:1128 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 7 37 dep non-fucosylated 1098:1112 arg1 diantennary 1131:1141 diantennary 1131:1141 diantennary 1131:1141 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 7 37 dep non-fucosylated 1098:1112 arg1 tetraantennary 1176:1189 tetraantennary 1176:1189 tetraantennary 1176:1189 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 7 38 dep [formula 1267:1274 arg1 see 1277:1279 see 1277:1279 see text 1277:1284 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 4 39 theme sulfated 497:504 arg1 chains 531:536 the intact (sulfated) sialylated carbohydrate chains 485:536 the intact (sulfated) sialylated carbohydrate chains 485:536 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 5 40 theme oligosaccharides 872:887 arg1 mixtures 860:867 mixtures 860:867 mixtures of oligosaccharides 860:887 In total, more than 150 carbohydrate-containing fractions were obtained, some of which still contained mixtures of oligosaccharides. 1425697 4 41 theme techniques 600:609 arg1 combination 556:566 a combination 554:566 a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1 554:754 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 42 theme carbohydrate 518:529 arg1 chains 531:536 the intact (sulfated) sialylated carbohydrate chains 485:536 the intact (sulfated) sialylated carbohydrate chains 485:536 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 3 43 link Asn-linked 255:264 arg1 chains 279:284 The Asn-linked carbohydrate chains 251:284 The Asn-linked carbohydrate chains 251:284 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 0 44 theme glycoprotein 58:69 arg1 chains 28:33 The Asn-linked carbohydrate chains 0:33 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male 0:81 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. 1425697 4 45 theme liquid-chromatographic 577:598 arg1 chromatography 725:738 high-pH anion-exchange chromatography 702:738 high-pH anion-exchange chromatography on CarboPac PA1 702:754 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 45 theme liquid-chromatographic 577:598 arg1 HPLC 673:676 amine-adsorption HPLC 656:676 amine-adsorption HPLC on Lichrospher-NH2 656:695 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 45 theme liquid-chromatographic 577:598 arg1 FPLC 635:638 anion-exchange FPLC 620:638 anion-exchange FPLC on Q-Sepharose 620:653 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 45 theme liquid-chromatographic 577:598 arg1 techniques 600:609 three liquid-chromatographic techniques 571:609 three liquid-chromatographic techniques 571:609 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 3 46 theme asparagine 354:363 arg1 F 373:373 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 315:373 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 315:373 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 4 47 theme sialylated 507:516 arg1 chains 531:536 the intact (sulfated) sialylated carbohydrate chains 485:536 the intact (sulfated) sialylated carbohydrate chains 485:536 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 3 48 from chromatography 435:448 arg1 P-100 461:465 Bio-Gel P-100 453:465 Bio-Gel P-100 453:465 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 1 49 theme N-acetylgalactosamine-containing 109:140 arg1 chains 164:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains. 1425697 0 50 theme Tamm-Horsfall 44:56 arg1 glycoprotein 58:69 human Tamm-Horsfall glycoprotein 38:69 human Tamm-Horsfall glycoprotein of one male 38:81 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. 1425697 7 51 gly non-fucosylated 1098:1112 arg1 chains 1204:1209 non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains 1098:1209 non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains 1098:1209 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 3 52 theme amidase 365:371 arg1 F 373:373 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 315:373 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 315:373 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 7 53 theme carbohydrate 1191:1202 arg1 chains 1204:1209 non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains 1098:1209 non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains 1098:1209 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 2 54 theme male 245:248 arg1 urine 232:236 the urine 228:236 the urine of one male 228:248 Human Tamm-Horsfall glycoprotein has been purified from the urine of one male. 1425697 1 55 theme N-linked 142:149 arg1 chains 164:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains. 1425697 3 56 theme N-acetyl-beta-glucosaminyl 327:352 arg1 F 373:373 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 315:373 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 315:373 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 7 57 theme non-fucosylated 1098:1112 arg1 chains 1204:1209 non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains 1098:1209 non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains 1098:1209 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 1 58 theme carbohydrate 151:162 arg1 chains 164:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains. 1425697 1 59 link N-linked 142:149 arg1 chains 164:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains 84:169 Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains. 1425697 4 60 gly sialylated 507:516 arg1 chains 531:536 the intact (sulfated) sialylated carbohydrate chains 485:536 the intact (sulfated) sialylated carbohydrate chains 485:536 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 4 61 theme intact 489:494 arg1 chains 531:536 the intact (sulfated) sialylated carbohydrate chains 485:536 the intact (sulfated) sialylated carbohydrate chains 485:536 Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. 1425697 6 62 theme one- 985:988 arg1 spectroscopy 1017:1028 one- and two-dimensional 1H-NMR spectroscopy 985:1028 one- and two-dimensional 1H-NMR spectroscopy 985:1028 The primary structure of 30 N-glycans, including 10 novel oligosaccharides, were determined by one- and two-dimensional 1H-NMR spectroscopy at 500 MHz or 600 MHz. 1425697 7 63 dep types 1057:1061 arg1 [formula 1267:1274 [formula 1267:1274 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1053:1285 The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] 1425697 3 64 theme Bio-Gel 453:459 arg1 P-100 461:465 Bio-Gel P-100 453:465 Bio-Gel P-100 453:465 The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. 1425697 0 65 gly glycoprotein 58:69 arg1 glycoprotein 58:69 human Tamm-Horsfall glycoprotein 38:69 human Tamm-Horsfall glycoprotein of one male 38:81 The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. 8404899 8 0 from oligosaccharides 1077:1092 arg1 juice 1129:1133 the pancreatic juice 1114:1133 the pancreatic juice of a normal donor 1114:1151 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 9 1 theme process 1261:1267 arg1 Alteration 1232:1241 Alteration 1232:1241 Alteration of the maturation process 1232:1267 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 3 2 theme pancreatic 515:524 arg1 juice 526:530 human pancreatic juice 509:530 human pancreatic juice 509:530 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 9 3 from patient 1333:1339 arg1 variant 1318:1324 a bile-salt-dependent-lipase variant 1289:1324 a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis 1289:1375 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 11 4 theme oligosaccharide 1758:1772 arg1 structure 1774:1782 the O-linked oligosaccharide structure 1745:1782 the O-linked oligosaccharide structure 1745:1782 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 8 5 theme N-linked 1068:1075 arg1 oligosaccharides 1077:1092 the N-linked oligosaccharides 1064:1092 the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor 1064:1151 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 3 6 from protein 498:504 arg1 juice 526:530 human pancreatic juice 509:530 human pancreatic juice 509:530 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 2 7 gly glycoprotein 276:287 arg1 glycoprotein 276:287 only a 100-kDa glycoprotein 261:287 only a 100-kDa glycoprotein 261:287 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 4 8 theme pancreatic 675:684 arg1 juice 686:690 human pancreatic juice 669:690 human pancreatic juice 669:690 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 3 9 theme bile-salt-dependent 598:616 arg1 lipase 618:623 the bile-salt-dependent lipase 594:623 the bile-salt-dependent lipase 594:623 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 3 9 theme bile-salt-dependent 598:616 arg1 protein 471:477 This protein 466:477 This protein 466:477 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 8 10 from juice 1129:1133 arg1 oligosaccharides 1077:1092 the N-linked oligosaccharides 1064:1092 the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor 1064:1151 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 8 10 from juice 1129:1133 arg1 variant 1101:1107 the variant 1097:1107 the variant from the pancreatic juice of a normal donor 1097:1151 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 10 11 theme sugar 1506:1510 arg1 sugar 1506:1510 sugar 1506:1510 sugar 1506:1510 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 10 11 theme sugar 1506:1510 arg1 amount 1496:1501 The amount 1492:1501 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity 1492:1587 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 6 12 contain have 881:884 arg2 composition 929:939 amino-acid composition 918:939 amino-acid composition 918:939 The purified variants have an identical molecular mass and amino-acid composition. 8404899 6 12 contain have 881:884 arg2 mass 909:912 an identical molecular mass 886:912 an identical molecular mass 886:912 The purified variants have an identical molecular mass and amino-acid composition. 8404899 6 12 contain have 881:884 arg1 variants 872:879 The purified variants 859:879 The purified variants 859:879 The purified variants have an identical molecular mass and amino-acid composition. 8404899 9 13 with compatible 1416:1425 arg1 predominance 1436:1447 the predominance 1432:1447 the predominance of hybrid or high-mannose-type structures 1432:1489 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 0 14 theme lipase 71:76 arg1 glycosylation 17:29 the glycosylation 13:29 the glycosylation of human pancreatic bile-salt-dependent lipase 13:76 Variation of the glycosylation of human pancreatic bile-salt-dependent lipase. 8404899 2 15 theme 100-kDa 268:274 arg1 glycoprotein 276:287 only a 100-kDa glycoprotein 261:287 only a 100-kDa glycoprotein 261:287 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 10 16 gly sialylated 1685:1694 arg1 structures 1664:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures 1614:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated 1614:1710 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 4 17 theme lipase 739:744 arg1 glycosylation 702:714 only the glycosylation 693:714 only the glycosylation of bile-salt-dependent lipase 693:744 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 9 18 theme carbohydrate 1388:1399 arg1 compatible 1416:1425 compatible 1416:1425 compatible 1416:1425 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 9 18 theme carbohydrate 1388:1399 arg1 composition 1401:1411 the carbohydrate composition 1384:1411 the carbohydrate composition 1384:1411 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 8 19 theme variant 1101:1107 arg1 oligosaccharides 1077:1092 the N-linked oligosaccharides 1064:1092 the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor 1064:1151 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 10 20 theme peanut 1560:1565 arg1 agglutinin 1567:1576 the peanut agglutinin 1556:1576 the peanut agglutinin reactivity 1556:1587 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 4 21 gly glycosylated 636:647 arg1 proteins 649:656 the glycosylated proteins 632:656 the glycosylated proteins present in human pancreatic juice 632:690 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 0 22 theme human 34:38 arg1 lipase 71:76 human pancreatic bile-salt-dependent lipase 34:76 human pancreatic bile-salt-dependent lipase 34:76 Variation of the glycosylation of human pancreatic bile-salt-dependent lipase. 8404899 2 23 theme pancreatic 397:406 arg1 juice 408:412 the pancreatic juice 393:412 the pancreatic juice from a patient suffering from chronic pancreatitis 393:463 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 11 24 link O-linked 1749:1756 arg1 structure 1774:1782 the O-linked oligosaccharide structure 1745:1782 the O-linked oligosaccharide structure 1745:1782 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 1 25 theme pancreatic 102:111 arg1 juice 113:117 human pancreatic juice 96:117 human pancreatic juice 96:117 Glycoproteins of human pancreatic juice were characterized by means of lectins after electrophoresis and electrotransfer to nitrocellulose membranes. 8404899 10 26 theme beta 1632:1635 arg1 structures 1664:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures 1614:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated 1614:1710 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 9 27 theme hybrid 1452:1457 arg1 predominance 1436:1447 the predominance 1432:1447 the predominance of hybrid or high-mannose-type structures 1432:1489 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 8 28 theme donor 1147:1151 arg1 juice 1129:1133 the pancreatic juice 1114:1133 the pancreatic juice of a normal donor 1114:1151 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 10 29 theme minimal 1620:1626 arg1 structures 1664:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures 1614:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated 1614:1710 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 5 30 theme human 834:838 arg1 juices 851:856 normal or pathological human pancreatic juices 811:856 normal or pathological human pancreatic juices 811:856 The enzyme was isolated either from normal or pathological human pancreatic juices. 8404899 9 31 theme high-mannose-type 1462:1478 arg1 structures 1480:1489 high-mannose-type structures 1462:1489 high-mannose-type structures 1462:1489 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 11 32 from unchanged 1798:1806 arg1 variants 1815:1822 the variants 1811:1822 the variants isolated from the pathological pancreatic juice 1811:1870 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 11 33 theme pathological 1842:1853 arg1 juice 1866:1870 the pathological pancreatic juice 1838:1870 the pathological pancreatic juice 1838:1870 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 2 34 theme pancreatic 360:369 arg1 disorder 371:378 any pancreatic disorder 356:378 any pancreatic disorder 356:378 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 8 35 link N-linked 1068:1075 arg1 oligosaccharides 1077:1092 the N-linked oligosaccharides 1064:1092 the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor 1064:1151 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 6 36 theme molecular 899:907 arg1 mass 909:912 an identical molecular mass 886:912 an identical molecular mass 886:912 The purified variants have an identical molecular mass and amino-acid composition. 8404899 0 37 gly glycosylation 17:29 arg1 lipase 71:76 human pancreatic bile-salt-dependent lipase 34:76 human pancreatic bile-salt-dependent lipase 34:76 Variation of the glycosylation of human pancreatic bile-salt-dependent lipase. 8404899 10 38 theme O-glycan 1655:1662 arg1 structures 1664:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures 1614:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated 1614:1710 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 11 39 attach isolated 1824:1831 arg2 variants 1815:1822 the variants 1811:1822 the variants isolated from the pathological pancreatic juice 1811:1870 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 11 39 attach isolated 1824:1831 arg1 juice 1866:1870 the pathological pancreatic juice 1838:1870 the pathological pancreatic juice 1838:1870 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 2 40 from patient 421:427 arg1 juice 408:412 the pancreatic juice 393:412 the pancreatic juice from a patient suffering from chronic pancreatitis 393:463 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 7 41 theme affinity 967:974 arg1 studies 976:982 lectin affinity studies 960:982 lectin affinity studies 960:982 As suspected from lectin affinity studies, the oligosaccharide composition differs between the variants. 8404899 0 42 theme bile-salt-dependent 51:69 arg1 lipase 71:76 human pancreatic bile-salt-dependent lipase 34:76 human pancreatic bile-salt-dependent lipase 34:76 Variation of the glycosylation of human pancreatic bile-salt-dependent lipase. 8404899 4 43 theme glycosylated 636:647 arg1 proteins 649:656 the glycosylated proteins 632:656 the glycosylated proteins present in human pancreatic juice 632:690 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 9 44 theme maturation 1250:1259 arg1 process 1261:1267 the maturation process 1246:1267 the maturation process 1246:1267 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 3 45 theme human 509:513 arg1 juice 526:530 human pancreatic juice 509:530 human pancreatic juice 509:530 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 8 46 theme N-glycan 1222:1229 arg1 maturation 1193:1202 maturation 1193:1202 maturation 1193:1202 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 8 46 theme N-glycan 1222:1229 arg1 processing 1178:1187 complete processing 1169:1187 complete processing 1169:1187 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 6 47 theme purified 863:870 arg1 variants 872:879 The purified variants 859:879 The purified variants 859:879 The purified variants have an identical molecular mass and amino-acid composition. 8404899 3 48 gly O-glycosylated 541:554 arg1 protein 498:504 the only protein 489:504 the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated 489:573 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 3 48 gly O-glycosylated 541:554 arg1 O-glycosylated 541:554 O-glycosylated 541:554 O-glycosylated 541:554 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 3 48 gly O-glycosylated 541:554 arg1 protein 471:477 This protein 466:477 This protein 466:477 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 2 49 theme pancreatic 303:312 arg1 juice 314:318 the pancreatic juice 299:318 the pancreatic juice from a normal patient 299:340 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 0 50 theme pancreatic 40:49 arg1 lipase 71:76 human pancreatic bile-salt-dependent lipase 34:76 human pancreatic bile-salt-dependent lipase 34:76 Variation of the glycosylation of human pancreatic bile-salt-dependent lipase. 8404899 5 51 dep juices 851:856 arg1 either 799:804 either 799:804 either 799:804 The enzyme was isolated either from normal or pathological human pancreatic juices. 8404899 8 52 theme oligosaccharides 1077:1092 arg1 structure 1051:1059 The structure 1047:1059 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor 1047:1151 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 4 53 from juice 686:690 arg1 present 658:664 present 658:664 present 658:664 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 1 54 theme nitrocellulose 203:216 arg1 membranes 218:226 nitrocellulose membranes 203:226 nitrocellulose membranes 203:226 Glycoproteins of human pancreatic juice were characterized by means of lectins after electrophoresis and electrotransfer to nitrocellulose membranes. 8404899 2 55 theme detected 237:244 arg1 glycoproteins 246:258 the detected glycoproteins 233:258 the detected glycoproteins 233:258 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 2 56 dep varied 289:294 arg1 i.e. 343:346 i.e. 343:346 i.e. 343:346 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 9 57 theme bile-salt-dependent-lipase 1291:1316 arg1 variant 1318:1324 a bile-salt-dependent-lipase variant 1289:1324 a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis 1289:1375 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 2 58 theme normal 327:332 arg1 patient 334:340 a normal patient 325:340 a normal patient 325:340 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 4 59 theme present 658:664 arg1 proteins 649:656 the glycosylated proteins 632:656 the glycosylated proteins present in human pancreatic juice 632:690 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 4 60 from present 658:664 arg1 juice 686:690 human pancreatic juice 669:690 human pancreatic juice 669:690 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 4 61 theme human 669:673 arg1 juice 686:690 human pancreatic juice 669:690 human pancreatic juice 669:690 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 2 62 gly glycoproteins 246:258 arg1 glycoproteins 246:258 the detected glycoproteins 233:258 the detected glycoproteins 233:258 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 4 63 gly glycosylation 702:714 arg1 lipase 739:744 bile-salt-dependent lipase 719:744 bile-salt-dependent lipase 719:744 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 9 64 theme chronic 1356:1362 arg1 pancreatitis 1364:1375 chronic pancreatitis 1356:1375 chronic pancreatitis 1356:1375 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 5 65 theme normal 811:816 arg1 juices 851:856 normal or pathological human pancreatic juices 811:856 normal or pathological human pancreatic juices 811:856 The enzyme was isolated either from normal or pathological human pancreatic juices. 8404899 10 66 theme agglutinin 1567:1576 arg1 reactivity 1578:1587 the peanut agglutinin reactivity 1556:1587 the peanut agglutinin reactivity 1556:1587 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 4 67 theme bile-salt-dependent 719:737 arg1 lipase 739:744 bile-salt-dependent lipase 719:744 bile-salt-dependent lipase 719:744 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 8 68 theme pancreatic 1118:1127 arg1 juice 1129:1133 the pancreatic juice 1114:1133 the pancreatic juice of a normal donor 1114:1151 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 2 69 from patient 334:340 arg1 juice 314:318 the pancreatic juice 299:318 the pancreatic juice from a normal patient 299:340 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 8 70 theme normal 1140:1145 arg1 donor 1147:1151 a normal donor 1138:1151 a normal donor 1138:1151 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 1 71 theme human 96:100 arg1 juice 113:117 human pancreatic juice 96:117 human pancreatic juice 96:117 Glycoproteins of human pancreatic juice were characterized by means of lectins after electrophoresis and electrotransfer to nitrocellulose membranes. 8404899 11 72 from variants 1815:1822 arg1 unchanged 1798:1806 unchanged 1798:1806 unchanged 1798:1806 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 11 72 from variants 1815:1822 arg1 sugar 1727:1731 sugar 1727:1731 sugar 1727:1731 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 11 72 from variants 1815:1822 arg1 amount 1717:1722 The amount 1713:1722 The amount of sugar involved in the O-linked oligosaccharide structure 1713:1782 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 0 73 theme glycosylation 17:29 arg1 Variation 0:8 Variation 0:8 Variation of the glycosylation of human pancreatic bile-salt-dependent lipase 0:76 Variation of the glycosylation of human pancreatic bile-salt-dependent lipase. 8404899 7 74 theme oligosaccharide 989:1003 arg1 composition 1005:1015 the oligosaccharide composition 985:1015 the oligosaccharide composition 985:1015 As suspected from lectin affinity studies, the oligosaccharide composition differs between the variants. 8404899 1 75 theme juice 113:117 arg1 Glycoproteins 79:91 Glycoproteins 79:91 Glycoproteins of human pancreatic juice 79:117 Glycoproteins of human pancreatic juice were characterized by means of lectins after electrophoresis and electrotransfer to nitrocellulose membranes. 8404899 2 76 theme chronic 444:450 arg1 pancreatitis 452:463 chronic pancreatitis 444:463 chronic pancreatitis 444:463 For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. 8404899 10 77 theme Gal 1628:1630 arg1 structures 1664:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures 1614:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated 1614:1710 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 11 78 theme pancreatic 1855:1864 arg1 juice 1866:1870 the pathological pancreatic juice 1838:1870 the pathological pancreatic juice 1838:1870 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 5 79 theme pathological 821:832 arg1 juices 851:856 normal or pathological human pancreatic juices 811:856 normal or pathological human pancreatic juices 811:856 The enzyme was isolated either from normal or pathological human pancreatic juices. 8404899 8 80 theme complete 1169:1176 arg1 processing 1178:1187 complete processing 1169:1187 complete processing 1169:1187 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 6 81 theme amino-acid 918:927 arg1 composition 929:939 amino-acid composition 918:939 amino-acid composition 918:939 The purified variants have an identical molecular mass and amino-acid composition. 8404899 5 82 theme pancreatic 840:849 arg1 juices 851:856 normal or pathological human pancreatic juices 811:856 normal or pathological human pancreatic juices 811:856 The enzyme was isolated either from normal or pathological human pancreatic juices. 8404899 9 83 theme structures 1480:1489 arg1 predominance 1436:1447 the predominance 1432:1447 the predominance of hybrid or high-mannose-type structures 1432:1489 Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. 8404899 10 84 theme structures 1664:1673 arg1 presence 1602:1609 the presence 1598:1609 the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated 1598:1710 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 4 85 attach present 658:664 arg2 proteins 649:656 the glycosylated proteins 632:656 the glycosylated proteins present in human pancreatic juice 632:690 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 4 85 attach present 658:664 arg1 juice 686:690 human pancreatic juice 669:690 human pancreatic juice 669:690 Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. 8404899 11 86 theme sugar 1727:1731 arg1 unchanged 1798:1806 unchanged 1798:1806 unchanged 1798:1806 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 11 86 theme sugar 1727:1731 arg1 sugar 1727:1731 sugar 1727:1731 sugar 1727:1731 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 11 86 theme sugar 1727:1731 arg1 amount 1717:1722 The amount 1713:1722 The amount of sugar involved in the O-linked oligosaccharide structure 1713:1782 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 6 87 theme identical 889:897 arg1 mass 909:912 an identical molecular mass 886:912 an identical molecular mass 886:912 The purified variants have an identical molecular mass and amino-acid composition. 8404899 11 88 theme O-linked 1749:1756 arg1 structure 1774:1782 the O-linked oligosaccharide structure 1745:1782 the O-linked oligosaccharide structure 1745:1782 The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice. 8404899 10 89 theme 1-->3GalNac-->T/S 1637:1653 arg1 structures 1664:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures 1614:1673 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated 1614:1710 The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. 8404899 3 90 theme only 493:496 arg1 protein 498:504 the only protein 489:504 the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated 489:573 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 3 90 theme only 493:496 arg1 O-glycosylated 541:554 O-glycosylated 541:554 O-glycosylated 541:554 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 3 90 theme only 493:496 arg1 protein 471:477 This protein 466:477 This protein 466:477 This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. 8404899 7 91 theme lectin 960:965 arg1 studies 976:982 lectin affinity studies 960:982 lectin affinity studies 960:982 As suspected from lectin affinity studies, the oligosaccharide composition differs between the variants. 8404899 8 92 theme complex-type 1209:1220 arg1 N-glycan 1222:1229 a complex-type N-glycan 1207:1229 a complex-type N-glycan 1207:1229 The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. 8404899 5 93 attach isolated 790:797 arg1 juices 851:856 normal or pathological human pancreatic juices 811:856 normal or pathological human pancreatic juices 811:856 The enzyme was isolated either from normal or pathological human pancreatic juices. 8404899 5 93 attach isolated 790:797 arg2 enzyme 779:784 The enzyme 775:784 The enzyme 775:784 The enzyme was isolated either from normal or pathological human pancreatic juices. 8687384 5 0 with consistent 1066:1075 arg1 expression 1086:1095 its expression 1082:1095 its expression in a cell line of neuroectodermal origin 1082:1136 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 1 1 theme chromatography 343:356 arg1 methods 309:315 methods 309:315 methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing 309:441 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 4 2 theme anti-carbohydrate 930:946 arg1 antibodies 968:977 anti-carbohydrate L2/HNK-1 monoclonal antibodies 930:977 anti-carbohydrate L2/HNK-1 monoclonal antibodies 930:977 Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies. 8687384 2 3 theme sole 606:609 arg1 group 619:623 their sole charged group 600:623 their sole charged group 600:623 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 4 4 contain containing 881:890 arg1 acid/sulphate 867:879 glucuronic acid/sulphate 856:879 glucuronic acid/sulphate containing N-linked glycans 856:907 Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies. 8687384 4 4 contain containing 881:890 arg2 glycans 901:907 N-linked glycans 892:907 N-linked glycans 892:907 Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies. 8687384 5 5 theme Bowes 996:1000 arg1 t-PA 1002:1005 Bowes t-PA 996:1005 Bowes t-PA 996:1005 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 2 6 theme charged 611:617 arg1 group 619:623 their sole charged group 600:623 their sole charged group 600:623 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 1 7 theme Bowes 262:266 arg1 line 282:285 the Bowes melanoma cell line 258:285 the Bowes melanoma cell line 258:285 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 2 8 theme Bowes 563:567 arg1 t-PA 569:572 Bowes t-PA 563:572 Bowes t-PA that carry sialic acid as their sole charged group 563:623 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 2 9 from discrepancy 476:486 arg1 literature 495:504 the literature 491:504 the literature 491:504 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 4 10 theme monoclonal 957:966 arg1 antibodies 968:977 anti-carbohydrate L2/HNK-1 monoclonal antibodies 930:977 anti-carbohydrate L2/HNK-1 monoclonal antibodies 930:977 Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies. 8687384 0 11 with mapping 73:79 arg1 antibodies 110:119 anti-L2/HNK-1 antibodies 96:119 anti-L2/HNK-1 antibodies 96:119 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 1 12 theme melanoma 268:275 arg1 line 282:285 the Bowes melanoma cell line 258:285 the Bowes melanoma cell line 258:285 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 1 13 theme Bio-Gel 371:377 arg1 chromatography 398:411 Bio-Gel P-4 gel filtration chromatography 371:411 Bio-Gel P-4 gel filtration chromatography 371:411 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 1 14 gly glycosylation 191:203 arg1 t-PA 238:241 t-PA 238:241 t-PA 238:241 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 1 14 gly glycosylation 191:203 arg1 activator 227:235 tissue plasminogen activator 208:235 tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line 208:285 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 2 15 theme terminal 666:673 arg1 residues 697:704 terminal N-acetylgalactosamine residues 666:704 terminal N-acetylgalactosamine residues 666:704 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 5 16 theme nervous 1048:1054 arg1 system 1056:1061 the nervous system 1044:1061 the nervous system 1044:1061 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 2 17 theme earlier 468:474 arg1 discrepancy 476:486 an earlier discrepancy 465:486 an earlier discrepancy in the literature 465:504 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 1 18 theme cell 277:280 arg1 line 282:285 the Bowes melanoma cell line 258:285 the Bowes melanoma cell line 258:285 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 1 19 theme P-4 379:381 arg1 chromatography 398:411 Bio-Gel P-4 gel filtration chromatography 371:411 Bio-Gel P-4 gel filtration chromatography 371:411 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 5 20 from presence 984:991 arg1 t-PA 1002:1005 Bowes t-PA 996:1005 Bowes t-PA 996:1005 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 5 21 from expression 1086:1095 arg1 line 1107:1110 a cell line 1100:1110 a cell line of neuroectodermal origin 1100:1136 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 4 22 link N-linked 892:899 arg1 glycans 901:907 N-linked glycans 892:907 N-linked glycans 892:907 Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies. 8687384 0 23 theme anti-L2/HNK-1 96:108 arg1 antibodies 110:119 anti-L2/HNK-1 antibodies 96:119 anti-L2/HNK-1 antibodies 96:119 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 1 24 theme gel 383:385 arg1 chromatography 398:411 Bio-Gel P-4 gel filtration chromatography 371:411 Bio-Gel P-4 gel filtration chromatography 371:411 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 2 25 contain carry 579:583 arg1 t-PA 569:572 Bowes t-PA 563:572 Bowes t-PA that carry sialic acid as their sole charged group 563:623 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 2 25 contain carry 579:583 arg2 acid 592:595 sialic acid 585:595 sialic acid 585:595 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 1 26 theme filtration 387:396 arg1 chromatography 398:411 Bio-Gel P-4 gel filtration chromatography 371:411 Bio-Gel P-4 gel filtration chromatography 371:411 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 2 27 theme core 643:646 arg1 fucosylated 648:658 core fucosylated 643:658 core fucosylated 643:658 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 2 28 theme complex 535:541 arg1 glycans 552:558 the major complex N-linked glycans 525:558 the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group 525:623 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 2 28 theme complex 535:541 arg1 bi-antennary 629:640 bi-antennary 629:640 bi-antennary 629:640 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 5 29 theme glycans 1010:1016 arg1 consistent 1066:1075 consistent 1066:1075 consistent 1066:1075 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 5 29 theme glycans 1010:1016 arg1 presence 984:991 The presence 980:991 The presence on Bowes t-PA of glycans associated primarily with the nervous system 980:1061 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 3 30 gly sialylated 794:803 arg1 glycans 805:811 related and previously unidentified sialylated glycans 758:811 related and previously unidentified sialylated glycans 758:811 We also report the characterization of a series of related and previously unidentified sialylated glycans. 8687384 3 31 theme sialylated 794:803 arg1 glycans 805:811 related and previously unidentified sialylated glycans 758:811 related and previously unidentified sialylated glycans 758:811 We also report the characterization of a series of related and previously unidentified sialylated glycans. 8687384 0 32 theme Bowes 21:25 arg1 activator 55:63 Bowes melanoma tissue plasminogen activator 21:63 Bowes melanoma tissue plasminogen activator 21:63 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 3 33 theme glycans 805:811 arg1 series 748:753 a series 746:753 a series of related and previously unidentified sialylated glycans 746:811 We also report the characterization of a series of related and previously unidentified sialylated glycans. 8687384 2 34 theme sialic 585:590 arg1 acid 592:595 sialic acid 585:595 sialic acid 585:595 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 0 35 with reaction 82:89 arg1 antibodies 110:119 anti-L2/HNK-1 antibodies 96:119 anti-L2/HNK-1 antibodies 96:119 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 1 36 theme tissue 208:213 arg1 t-PA 238:241 t-PA 238:241 t-PA 238:241 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 1 36 theme tissue 208:213 arg1 activator 227:235 tissue plasminogen activator 208:235 tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line 208:285 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 5 37 theme cell 1102:1105 arg1 line 1107:1110 a cell line 1100:1110 a cell line of neuroectodermal origin 1100:1136 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 1 38 theme plasminogen 215:225 arg1 t-PA 238:241 t-PA 238:241 t-PA 238:241 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 1 38 theme plasminogen 215:225 arg1 activator 227:235 tissue plasminogen activator 208:235 tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line 208:285 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 0 39 theme tissue 36:41 arg1 activator 55:63 Bowes melanoma tissue plasminogen activator 21:63 Bowes melanoma tissue plasminogen activator 21:63 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 3 40 theme unidentified 781:792 arg1 glycans 805:811 related and previously unidentified sialylated glycans 758:811 related and previously unidentified sialylated glycans 758:811 We also report the characterization of a series of related and previously unidentified sialylated glycans. 8687384 3 41 theme related 758:764 arg1 glycans 805:811 related and previously unidentified sialylated glycans 758:811 related and previously unidentified sialylated glycans 758:811 We also report the characterization of a series of related and previously unidentified sialylated glycans. 8687384 1 42 theme activator 227:235 arg1 glycosylation 191:203 The glycosylation 187:203 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line 187:285 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 0 43 theme melanoma 27:34 arg1 activator 55:63 Bowes melanoma tissue plasminogen activator 21:63 Bowes melanoma tissue plasminogen activator 21:63 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 1 44 theme exoglycosidase 417:430 arg1 sequencing 432:441 exoglycosidase sequencing 417:441 exoglycosidase sequencing 417:441 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 0 45 gly glycosylation 4:16 arg1 activator 55:63 Bowes melanoma tissue plasminogen activator 21:63 Bowes melanoma tissue plasminogen activator 21:63 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 2 46 theme N-linked 543:550 arg1 glycans 552:558 the major complex N-linked glycans 525:558 the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group 525:623 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 2 46 theme N-linked 543:550 arg1 bi-antennary 629:640 bi-antennary 629:640 bi-antennary 629:640 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 0 47 theme activator 55:63 arg1 glycosylation 4:16 The glycosylation 0:16 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 0:185 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 0 48 theme acid 162:165 arg1 glycans 178:184 sulphated/glucuronic acid containing glycans 141:184 sulphated/glucuronic acid containing glycans 141:184 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 5 49 attach presence 984:991 arg2 glycans 1010:1016 glycans 1010:1016 glycans associated primarily with the nervous system 1010:1061 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 5 49 attach presence 984:991 arg1 t-PA 1002:1005 Bowes t-PA 996:1005 Bowes t-PA 996:1005 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 4 50 theme N-linked 892:899 arg1 glycans 901:907 N-linked glycans 892:907 N-linked glycans 892:907 Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies. 8687384 3 51 theme series 748:753 arg1 characterization 726:741 the characterization 722:741 the characterization of a series of related and previously unidentified sialylated glycans 722:811 We also report the characterization of a series of related and previously unidentified sialylated glycans. 8687384 0 52 theme plasminogen 43:53 arg1 activator 55:63 Bowes melanoma tissue plasminogen activator 21:63 Bowes melanoma tissue plasminogen activator 21:63 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 1 53 theme serial 320:325 arg1 chromatography 343:356 serial lectin affinity chromatography 320:356 serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing 320:441 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 0 54 theme sulphated/glucuronic 141:160 arg1 glycans 178:184 sulphated/glucuronic acid containing glycans 141:184 sulphated/glucuronic acid containing glycans 141:184 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 2 55 from glycans 552:558 arg1 t-PA 569:572 Bowes t-PA 563:572 Bowes t-PA that carry sialic acid as their sole charged group 563:623 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 4 56 theme glucuronic 856:865 arg1 acid/sulphate 867:879 glucuronic acid/sulphate 856:879 glucuronic acid/sulphate containing N-linked glycans 856:907 Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies. 8687384 1 57 theme lectin 327:332 arg1 chromatography 343:356 serial lectin affinity chromatography 320:356 serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing 320:441 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 8687384 0 58 theme glycans 178:184 arg1 mapping 73:79 lectin mapping 66:79 lectin mapping 66:79 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 0 58 theme glycans 178:184 arg1 presence 129:136 the presence 125:136 the presence of sulphated/glucuronic acid containing glycans 125:184 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 0 58 theme glycans 178:184 arg1 reaction 82:89 reaction 82:89 reaction with anti-L2/HNK-1 antibodies 82:119 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 5 59 theme neuroectodermal 1115:1129 arg1 origin 1131:1136 neuroectodermal origin 1115:1136 neuroectodermal origin 1115:1136 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 4 60 theme Bowes 835:839 arg1 t-PA 841:844 Bowes t-PA 835:844 Bowes t-PA 835:844 Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies. 8687384 2 61 theme N-acetylgalactosamine 675:695 arg1 residues 697:704 terminal N-acetylgalactosamine residues 666:704 terminal N-acetylgalactosamine residues 666:704 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 0 62 with presence 129:136 arg1 antibodies 110:119 anti-L2/HNK-1 antibodies 96:119 anti-L2/HNK-1 antibodies 96:119 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 0 63 theme containing 167:176 arg1 glycans 178:184 sulphated/glucuronic acid containing glycans 141:184 sulphated/glucuronic acid containing glycans 141:184 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 5 64 theme origin 1131:1136 arg1 line 1107:1110 a cell line 1100:1110 a cell line of neuroectodermal origin 1100:1136 The presence on Bowes t-PA of glycans associated primarily with the nervous system is consistent with its expression in a cell line of neuroectodermal origin. 8687384 4 65 theme L2/HNK-1 948:955 arg1 antibodies 968:977 anti-carbohydrate L2/HNK-1 monoclonal antibodies 930:977 anti-carbohydrate L2/HNK-1 monoclonal antibodies 930:977 Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies. 8687384 2 66 with bi-antennary 629:640 arg1 residues 697:704 terminal N-acetylgalactosamine residues 666:704 terminal N-acetylgalactosamine residues 666:704 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 0 67 theme lectin 66:71 arg1 mapping 73:79 lectin mapping 66:79 lectin mapping 66:79 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 0 68 dep glycosylation 4:16 arg1 presence 129:136 the presence 125:136 the presence of sulphated/glucuronic acid containing glycans 125:184 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 0 68 dep glycosylation 4:16 arg1 mapping 73:79 lectin mapping 66:79 lectin mapping 66:79 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 0 68 dep glycosylation 4:16 arg1 reaction 82:89 reaction 82:89 reaction with anti-L2/HNK-1 antibodies 82:119 The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. 8687384 2 69 link N-linked 543:550 arg1 glycans 552:558 the major complex N-linked glycans 525:558 the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group 525:623 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 2 69 link N-linked 543:550 arg1 bi-antennary 629:640 bi-antennary 629:640 bi-antennary 629:640 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 2 70 theme major 529:533 arg1 glycans 552:558 the major complex N-linked glycans 525:558 the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group 525:623 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 2 70 theme major 529:533 arg1 bi-antennary 629:640 bi-antennary 629:640 bi-antennary 629:640 This study clarified an earlier discrepancy in the literature and confirmed that the major complex N-linked glycans on Bowes t-PA that carry sialic acid as their sole charged group are bi-antennary, core fucosylated, with terminal N-acetylgalactosamine residues. 8687384 1 71 theme affinity 334:341 arg1 chromatography 343:356 serial lectin affinity chromatography 320:356 serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing 320:441 The glycosylation of tissue plasminogen activator (t-PA) obtained from the Bowes melanoma cell line was re-examined using methods of serial lectin affinity chromatography coupled with Bio-Gel P-4 gel filtration chromatography and exoglycosidase sequencing. 3007481 0 0 theme mammary 87:93 arg1 cells 106:110 human mammary epithelial cells 81:110 human mammary epithelial cells 81:110 Structures of O-linked oligosaccharides present in the proteoglycans secreted by human mammary epithelial cells. 3007481 1 1 theme epithelial 339:348 arg1 line 355:358 human mammary epithelial cell line 325:358 human mammary epithelial cell line 325:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 1 2 from sulfate 195:201 arg1 present 172:178 present 172:178 present 172:178 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 8 3 from structure 1300:1308 arg1 mixture 1340:1346 the mixture 1336:1346 the mixture 1336:1346 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 6 4 theme high 907:910 arg1 electrophoresis 926:940 high voltage paper electrophoresis 907:940 high voltage paper electrophoresis 907:940 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 0 5 theme human 81:85 arg1 cells 106:110 human mammary epithelial cells 81:110 human mammary epithelial cells 81:110 Structures of O-linked oligosaccharides present in the proteoglycans secreted by human mammary epithelial cells. 3007481 1 6 theme cell 350:353 arg1 line 355:358 human mammary epithelial cell line 325:358 human mammary epithelial cell line 325:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 2 7 contain contain 430:436 arg1 types 400:404 Both proteoglycan types 382:404 Both proteoglycan types from the two cell lines 382:428 Both proteoglycan types from the two cell lines contain a series of O-linked oligosaccharides ranging in size from di- to hexasaccharide. 3007481 2 7 contain contain 430:436 arg2 series 440:445 a series 438:445 a series of O-linked oligosaccharides ranging in size from di- to hexasaccharide 438:517 Both proteoglycan types from the two cell lines contain a series of O-linked oligosaccharides ranging in size from di- to hexasaccharide. 3007481 1 8 theme normal 279:284 arg1 medium 267:272 the culture medium 255:272 the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line 255:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 0 9 link O-linked 14:21 arg1 oligosaccharides 23:38 O-linked oligosaccharides 14:38 O-linked oligosaccharides 14:38 Structures of O-linked oligosaccharides present in the proteoglycans secreted by human mammary epithelial cells. 3007481 8 10 theme valuable 1266:1273 arg1 tool 1275:1278 a valuable tool 1264:1278 a valuable tool 1264:1278 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 8 10 theme valuable 1266:1273 arg1 oxidation 1161:1169 Periodate oxidation 1151:1169 Periodate oxidation 1151:1169 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 6 11 theme filtration 892:901 arg1 combination 873:883 a combination 871:883 a combination of gel filtration and high voltage paper electrophoresis 871:940 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 0 12 theme epithelial 95:104 arg1 cells 106:110 human mammary epithelial cells 81:110 human mammary epithelial cells 81:110 Structures of O-linked oligosaccharides present in the proteoglycans secreted by human mammary epithelial cells. 3007481 1 13 attach present 172:178 arg1 proteoglycans 227:239 the heparan sulfate and chondroitin sulfate proteoglycans 183:239 proteoglycans 227:239 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 1 13 attach present 172:178 arg2 oligosaccharides 155:170 O-glycosidically linked oligosaccharides 131:170 O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line 131:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 1 13 attach present 172:178 arg1 sulfate 195:201 the heparan sulfate and chondroitin sulfate proteoglycans 183:239 sulfate 195:201 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 7 14 theme sugar 1033:1037 arg1 composition 1039:1049 sugar composition 1033:1049 sugar composition 1033:1049 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 9 15 dep see 1424:1426 arg1 Formula 1415:1421 Formula 1415:1421 Formula 1415:1421 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 3 16 dep described 650:658 arg1 1986 716:719 1986 716:719 1986 716:719 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 3 16 dep described 650:658 arg1 A 712:712 A 712:712 A 712:712 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 3 16 dep described 650:658 arg1 V. 688:689 V. 688:689 V. 688:689 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 3 16 dep described 650:658 arg1 D. 668:669 D. 668:669 D. 668:669 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 3 16 dep described 650:658 arg1 P. 691:692 P. 691:692 P. 691:692 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 3 16 dep described 650:658 arg1 C. 671:672 C. 671:672 C. 671:672 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 1 17 from present 172:178 arg1 proteoglycans 227:239 the heparan sulfate and chondroitin sulfate proteoglycans 183:239 proteoglycans 227:239 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 1 17 from present 172:178 arg1 sulfate 195:201 the heparan sulfate and chondroitin sulfate proteoglycans 183:239 sulfate 195:201 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 9 18 theme sialic 1470:1475 arg1 acid 1477:1480 sialic acid 1470:1480 sialic acid 1470:1480 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 9 19 theme oligosaccharides 1371:1386 arg1 follows 1405:1411 follows 1405:1411 follows 1405:1411 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 9 19 theme oligosaccharides 1371:1386 arg1 structures 1353:1362 The structures 1349:1362 The structures of the oligosaccharides 1349:1386 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 1 20 theme heparan 187:193 arg1 sulfate 195:201 the heparan sulfate and chondroitin sulfate proteoglycans 183:239 sulfate 195:201 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 6 21 theme gel 888:890 arg1 filtration 892:901 gel filtration 888:901 gel filtration 888:901 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 0 22 attach present 40:46 arg2 Structures 0:9 Structures 0:9 Structures of O-linked oligosaccharides 0:38 Structures of O-linked oligosaccharides present in the proteoglycans secreted by human mammary epithelial cells. 3007481 0 22 attach present 40:46 arg1 proteoglycans 55:67 the proteoglycans 51:67 the proteoglycans secreted by human mammary epithelial cells 51:110 Structures of O-linked oligosaccharides present in the proteoglycans secreted by human mammary epithelial cells. 3007481 6 23 theme electrophoresis 926:940 arg1 combination 873:883 a combination 871:883 a combination of gel filtration and high voltage paper electrophoresis 871:940 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 8 24 from components 1322:1331 arg1 mixture 1340:1346 the mixture 1336:1346 the mixture 1336:1346 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 6 25 theme alkaline 824:831 arg1 treatment 845:853 alkaline borohydride treatment 824:853 alkaline borohydride treatment 824:853 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 7 26 theme sequential 1088:1097 arg1 treatment 1114:1122 sequential exoglycosidase treatment 1088:1122 sequential exoglycosidase treatment 1088:1122 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 3 27 dep A 712:712 arg1 E. 709:710 E. 709:710 E. 709:710 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 7 28 theme oligosaccharides 990:1005 arg1 structures 947:956 The structures 943:956 The structures of two neutral and seven acidic oligosaccharides 943:1005 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 2 29 link O-linked 450:457 arg1 oligosaccharides 459:474 O-linked oligosaccharides 450:474 O-linked oligosaccharides ranging in size from di- to hexasaccharide 450:517 Both proteoglycan types from the two cell lines contain a series of O-linked oligosaccharides ranging in size from di- to hexasaccharide. 3007481 2 30 theme proteoglycan 387:398 arg1 types 400:404 Both proteoglycan types 382:404 Both proteoglycan types from the two cell lines 382:428 Both proteoglycan types from the two cell lines contain a series of O-linked oligosaccharides ranging in size from di- to hexasaccharide. 3007481 7 31 theme exoglycosidase 1099:1112 arg1 treatment 1114:1122 sequential exoglycosidase treatment 1088:1122 sequential exoglycosidase treatment 1088:1122 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 1 32 dep normal 279:284 arg1 line 355:358 human mammary epithelial cell line 325:358 human mammary epithelial cell line 325:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 9 33 theme ester 1486:1490 arg1 sulfate 1492:1498 ester sulfate 1486:1498 ester sulfate 1486:1498 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 8 34 theme tritium 1192:1198 arg1 advantage 1179:1187 advantage 1179:1187 advantage of tritium label 1179:1204 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 1 35 theme chondroitin 207:217 arg1 proteoglycans 227:239 the heparan sulfate and chondroitin sulfate proteoglycans 183:239 proteoglycans 227:239 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 0 36 theme oligosaccharides 23:38 arg1 Structures 0:9 Structures 0:9 Structures of O-linked oligosaccharides 0:38 Structures of O-linked oligosaccharides present in the proteoglycans secreted by human mammary epithelial cells. 3007481 8 37 theme sugars 1243:1248 arg1 positions 1218:1226 specific positions 1209:1226 specific positions of constituent sugars 1209:1248 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 8 38 theme constituent 1231:1241 arg1 sugars 1243:1248 constituent sugars 1231:1248 constituent sugars 1231:1248 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 1 39 theme sulfate 219:225 arg1 proteoglycans 227:239 the heparan sulfate and chondroitin sulfate proteoglycans 183:239 proteoglycans 227:239 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 0 40 theme O-linked 14:21 arg1 oligosaccharides 23:38 O-linked oligosaccharides 14:38 O-linked oligosaccharides 14:38 Structures of O-linked oligosaccharides present in the proteoglycans secreted by human mammary epithelial cells. 3007481 8 41 theme isomeric 1313:1320 arg1 components 1322:1331 isomeric components 1313:1331 isomeric components in the mixture 1313:1346 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 7 42 theme acidic 983:988 arg1 oligosaccharides 990:1005 two neutral and seven acidic oligosaccharides 961:1005 two neutral and seven acidic oligosaccharides 961:1005 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 6 43 theme O-linked 758:765 arg1 oligosaccharides 767:782 The O-linked oligosaccharides 754:782 The O-linked oligosaccharides 754:782 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 2 44 theme cell 419:422 arg1 lines 424:428 the two cell lines 411:428 the two cell lines 411:428 Both proteoglycan types from the two cell lines contain a series of O-linked oligosaccharides ranging in size from di- to hexasaccharide. 3007481 1 45 theme malignant 302:310 arg1 medium 267:272 the culture medium 255:272 the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line 255:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 7 46 theme neutral 965:971 arg1 oligosaccharides 990:1005 two neutral and seven acidic oligosaccharides 961:1005 two neutral and seven acidic oligosaccharides 961:1005 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 8 47 theme components 1322:1331 arg1 structure 1300:1308 the structure 1296:1308 the structure of isomeric components in the mixture 1296:1346 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 8 48 from mixture 1340:1346 arg1 structure 1300:1308 the structure 1296:1308 the structure of isomeric components in the mixture 1296:1346 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 8 49 theme specific 1209:1216 arg1 positions 1218:1226 specific positions 1209:1226 specific positions of constituent sugars 1209:1248 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 6 50 attach released 789:796 arg2 oligosaccharides 767:782 The O-linked oligosaccharides 754:782 The O-linked oligosaccharides 754:782 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 6 50 attach released 789:796 arg1 proteoglycans 807:819 the proteoglycans 803:819 the proteoglycans 803:819 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 3 51 dep C. 671:672 arg1 Biol 725:728 Biol 725:728 Biol 725:728 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 7 52 theme periodate 1067:1075 arg1 oxidation 1077:1085 periodate oxidation 1067:1085 periodate oxidation 1067:1085 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 7 53 theme oxidation 1077:1085 arg1 treatment 1114:1122 sequential exoglycosidase treatment 1088:1122 sequential exoglycosidase treatment 1088:1122 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 7 53 theme oxidation 1077:1085 arg1 composition 1039:1049 sugar composition 1033:1049 sugar composition 1033:1049 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 7 53 theme oxidation 1077:1085 arg1 results 1056:1062 the results 1052:1062 the results of periodate oxidation 1052:1085 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 7 53 theme oxidation 1077:1085 arg1 analysis 1141:1148 methylation analysis 1129:1148 methylation analysis 1129:1148 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 6 54 theme borohydride 833:843 arg1 treatment 845:853 alkaline borohydride treatment 824:853 alkaline borohydride treatment 824:853 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 2 55 theme oligosaccharides 459:474 arg1 series 440:445 a series 438:445 a series of O-linked oligosaccharides ranging in size from di- to hexasaccharide 438:517 Both proteoglycan types from the two cell lines contain a series of O-linked oligosaccharides ranging in size from di- to hexasaccharide. 3007481 3 56 theme glucosamine 567:577 arg1 presence 544:551 the presence 540:551 the presence of either [3H]glucosamine or [3H]galactose 540:594 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 3 56 theme glucosamine 567:577 arg1 35SO4 604:608 Na2 35SO4 600:608 Na2 35SO4 600:608 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 9 57 contain containing 1454:1463 arg1 novel 1503:1507 novel 1503:1507 novel 1503:1507 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 9 57 contain containing 1454:1463 arg2 sulfate 1492:1498 ester sulfate 1486:1498 ester sulfate 1486:1498 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 9 57 contain containing 1454:1463 arg2 acid 1477:1480 sialic acid 1470:1480 sialic acid 1470:1480 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 9 57 contain containing 1454:1463 arg1 oligosaccharide 1438:1452 The oligosaccharide 1434:1452 The oligosaccharide containing both sialic acid and ester sulfate 1434:1498 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 2 58 theme O-linked 450:457 arg1 oligosaccharides 459:474 O-linked oligosaccharides 450:474 O-linked oligosaccharides ranging in size from di- to hexasaccharide 450:517 Both proteoglycan types from the two cell lines contain a series of O-linked oligosaccharides ranging in size from di- to hexasaccharide. 3007481 1 59 link linked 148:153 arg1 oligosaccharides 155:170 O-glycosidically linked oligosaccharides 131:170 O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line 131:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 7 60 theme methylation 1129:1139 arg1 analysis 1141:1148 methylation analysis 1129:1148 methylation analysis 1129:1148 The structures of two neutral and seven acidic oligosaccharides were established based on sugar composition, the results of periodate oxidation, sequential exoglycosidase treatment, and methylation analysis. 3007481 1 61 theme human 325:329 arg1 line 355:358 human mammary epithelial cell line 325:358 human mammary epithelial cell line 325:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 9 62 dep follows 1405:1411 arg1 reported 1526:1533 reported 1526:1533 has not been reported previously 1513:1544 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 9 62 dep follows 1405:1411 arg1 novel 1503:1507 novel 1503:1507 novel 1503:1507 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 9 62 dep follows 1405:1411 arg1 see 1424:1426 see 1424:1426 see text 1424:1431 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 9 62 dep follows 1405:1411 arg1 oligosaccharide 1438:1452 The oligosaccharide 1434:1452 The oligosaccharide containing both sialic acid and ester sulfate 1434:1498 The structures of the oligosaccharides were assigned as follows: (Formula: see text) The oligosaccharide containing both sialic acid and ester sulfate is novel and has not been reported previously. 3007481 3 63 theme Na2 600:602 arg1 35SO4 604:608 Na2 35SO4 600:608 Na2 35SO4 600:608 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 1 64 from proteoglycans 227:239 arg1 present 172:178 present 172:178 present 172:178 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 6 65 link O-linked 758:765 arg1 oligosaccharides 767:782 The O-linked oligosaccharides 754:782 The O-linked oligosaccharides 754:782 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 8 66 dep tritium 1192:1198 arg1 label 1200:1204 label 1200:1204 label 1200:1204 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 8 67 theme Periodate 1151:1159 arg1 tool 1275:1278 a valuable tool 1264:1278 a valuable tool 1264:1278 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 8 67 theme Periodate 1151:1159 arg1 oxidation 1161:1169 Periodate oxidation 1151:1169 Periodate oxidation 1151:1169 Periodate oxidation, taking advantage of tritium label at specific positions of constituent sugars, proved to be a valuable tool in establishing the structure of isomeric components in the mixture. 3007481 1 68 theme linked 148:153 arg1 oligosaccharides 155:170 O-glycosidically linked oligosaccharides 131:170 O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line 131:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 1 69 theme culture 259:265 arg1 medium 267:272 the culture medium 255:272 the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line 255:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 1 70 attach isolated 241:248 arg1 medium 267:272 the culture medium 255:272 the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line 255:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 1 70 attach isolated 241:248 arg2 sulfate 195:201 the heparan sulfate and chondroitin sulfate proteoglycans 183:239 sulfate 195:201 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 3 71 theme galactose 586:594 arg1 presence 544:551 the presence 540:551 the presence of either [3H]glucosamine or [3H]galactose 540:594 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 3 71 theme galactose 586:594 arg1 35SO4 604:608 Na2 35SO4 600:608 Na2 35SO4 600:608 Cells were grown in the presence of either [3H]glucosamine or [3H]galactose and Na2 35SO4, and the proteoglycans were isolated as described (Gowda, D. C., Bhavanandan, V. P., and Davidson, E. A. (1986) J. Biol. 3007481 1 72 theme oligosaccharides 155:170 arg1 structures 117:126 The structures 113:126 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line 113:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 6 73 theme paper 920:924 arg1 electrophoresis 926:940 high voltage paper electrophoresis 907:940 high voltage paper electrophoresis 907:940 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 3007481 1 74 theme mammary 331:337 arg1 line 355:358 human mammary epithelial cell line 325:358 human mammary epithelial cell line 325:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 5 75 dep 261 737:739 arg1 4926-4934 742:750 4926-4934 742:750 4926-4934 742:750 261, 4926-4934). 3007481 2 76 from lines 424:428 arg1 types 400:404 Both proteoglycan types 382:404 Both proteoglycan types from the two cell lines 382:428 Both proteoglycan types from the two cell lines contain a series of O-linked oligosaccharides ranging in size from di- to hexasaccharide. 3007481 1 77 theme present 172:178 arg1 oligosaccharides 155:170 O-glycosidically linked oligosaccharides 131:170 O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line 131:358 The structures of O-glycosidically linked oligosaccharides present in the heparan sulfate and chondroitin sulfate proteoglycans isolated from the culture medium of a normal (HBL-100) and a malignant (MDA-MB-231) human mammary epithelial cell line have been determined. 3007481 6 78 theme voltage 912:918 arg1 electrophoresis 926:940 high voltage paper electrophoresis 907:940 high voltage paper electrophoresis 907:940 The O-linked oligosaccharides were released from the proteoglycans by alkaline borohydride treatment and purified by a combination of gel filtration and high voltage paper electrophoresis. 7763244 3 0 from terminus 624:631 arg1 truncation 597:606 extensive truncation 587:606 extensive truncation at the carboxyl terminus 587:631 The antibody against the N-terminal half of amyloid beta-protein showed no immunoreactivity with S-APPs, suggesting extensive truncation at the carboxyl terminus. 7763244 4 1 theme trimannosyl 809:819 arg1 core 821:824 a fucosylated trimannosyl core 795:824 a fucosylated trimannosyl core 795:824 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 0 2 link N-linked 0:7 arg1 oligosaccharide 9:23 N-linked oligosaccharide 0:23 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 0:137 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 6 3 theme beta 1084:1087 arg1 structures 1089:1098 Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures 1037:1098 Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures 1037:1098 However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. 7763244 6 4 theme alpha 1069:1073 arg1 beta 1084:1087 Sia alpha 2-->6Gal beta 1065:1087 Sia alpha 2-->6Gal beta 1065:1087 However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. 7763244 5 5 contain have 893:896 arg1 L-APPs 871:876 L-APPs 871:876 L-APPs 871:876 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 5 5 contain have 893:896 arg2 structures 972:981 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures 898:981 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures 898:981 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 5 6 dep beta 939:942 arg1 Fuc 920:922 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta 898:942 Fuc 920:922 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 1 7 theme oligosaccharide 165:179 arg1 structure 181:189 the N-linked oligosaccharide structure 152:189 the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP) 152:234 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 0 8 theme regulatory 99:108 arg1 role 110:113 putative regulatory role 90:113 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 0:137 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 1 9 theme C6 345:346 arg1 cells 355:359 cDNA-transfected C6 glioma cells 328:359 cDNA-transfected C6 glioma cells 328:359 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 1 10 theme precursor 207:215 arg1 protein 217:223 beta-amyloid precursor protein 194:223 beta-amyloid precursor protein (beta APP) 194:234 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 1 10 theme precursor 207:215 arg1 APP 231:233 beta APP 226:233 beta APP 226:233 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 7 11 theme chains 1268:1273 arg1 structure 1245:1253 the fine structure 1236:1253 the fine structure of its sugar chains 1236:1273 The present results suggest that the processing of beta APP may be regulated via the heterogeneity in the fine structure of its sugar chains. 7763244 0 12 theme APP 123:125 arg1 processing 127:136 beta APP processing 118:136 beta APP processing 118:136 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 5 13 theme 2-->6Gal 958:965 arg1 beta 967:970 Sia alpha 2-->6Gal beta 948:970 Sia alpha 2-->6Gal beta 948:970 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 3 14 theme amyloid 515:521 arg1 beta-protein 523:534 amyloid beta-protein 515:534 amyloid beta-protein 515:534 The antibody against the N-terminal half of amyloid beta-protein showed no immunoreactivity with S-APPs, suggesting extensive truncation at the carboxyl terminus. 7763244 4 15 theme bisecting 832:840 arg1 residue 849:855 a bisecting GlcNAc residue 830:855 a bisecting GlcNAc residue 830:855 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 4 16 theme main 665:668 arg1 structure 670:678 the main structure 661:678 the main structure of the N-linked oligosaccharide shared by L- and S-APPs 661:734 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 4 17 with bi- 757:759 arg1 residue 849:855 a bisecting GlcNAc residue 830:855 a bisecting GlcNAc residue 830:855 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 4 17 with bi- 757:759 arg1 core 821:824 a fucosylated trimannosyl core 795:824 a fucosylated trimannosyl core 795:824 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 4 18 theme blot 646:649 arg1 analysis 651:658 lectin blot analysis 639:658 lectin blot analysis 639:658 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 1 19 theme conditioned 297:307 arg1 medium 309:314 the conditioned medium 293:314 the conditioned medium of beta APP cDNA-transfected C6 glioma cells 293:359 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 4 20 with triantennary 764:775 arg1 residue 849:855 a bisecting GlcNAc residue 830:855 a bisecting GlcNAc residue 830:855 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 4 20 with triantennary 764:775 arg1 core 821:824 a fucosylated trimannosyl core 795:824 a fucosylated trimannosyl core 795:824 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 0 21 theme glioma 76:81 arg1 cells 83:87 C6 glioma cells 73:87 C6 glioma cells 73:87 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 2 22 dep APPs 420:423 arg1 S-APPs 448:453 S-APPs 448:453 S-APPs 448:453 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 2 22 dep APPs 420:423 arg1 L-APPs 426:431 L-APPs 426:431 L-APPs 426:431 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 2 22 dep APPs 420:423 arg1 APPs 442:445 smaller APPs 434:445 smaller APPs 434:445 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 5 23 theme Gal 898:900 arg1 beta 939:942 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta 898:942 beta 939:942 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 1 24 link N-linked 156:163 arg1 structure 181:189 the N-linked oligosaccharide structure 152:189 the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP) 152:234 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 5 25 theme 1-->4GlcNAc 907:917 arg1 beta 939:942 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta 898:942 beta 939:942 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 7 26 theme fine 1240:1243 arg1 structure 1245:1253 the fine structure 1236:1253 the fine structure of its sugar chains 1236:1273 The present results suggest that the processing of beta APP may be regulated via the heterogeneity in the fine structure of its sugar chains. 7763244 0 27 theme N-linked 0:7 arg1 oligosaccharide 9:23 N-linked oligosaccharide 0:23 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 0:137 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 2 28 theme different 385:393 arg1 weight 405:410 different molecular weight 385:410 different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) 385:454 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 2 28 theme different 385:393 arg1 APPs 420:423 larger APPs 413:423 larger APPs 413:423 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 4 29 theme N-linked 687:694 arg1 oligosaccharide 696:710 the N-linked oligosaccharide 683:710 the N-linked oligosaccharide shared by L- and S-APPs 683:734 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 0 30 dep oligosaccharide 9:23 arg1 role 110:113 putative regulatory role 90:113 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 0:137 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 2 31 theme APPs 375:378 arg1 types 366:370 Two types 362:370 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) 362:454 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 1 32 theme APP 264:266 arg1 derivative 245:254 soluble derivative 237:254 soluble derivative of beta APP (APPs) 237:273 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 0 33 theme precursor 41:49 arg1 protein 51:57 beta-amyloid precursor protein 28:57 beta-amyloid precursor protein (beta APP) of C6 glioma cells 28:87 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 0 33 theme precursor 41:49 arg1 APP 65:67 beta APP 60:67 beta APP 60:67 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 2 34 theme larger 413:418 arg1 weight 405:410 different molecular weight 385:410 different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) 385:454 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 2 34 theme larger 413:418 arg1 APPs 420:423 larger APPs 413:423 larger APPs 413:423 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 5 35 theme alpha 952:956 arg1 beta 967:970 Sia alpha 2-->6Gal beta 948:970 Sia alpha 2-->6Gal beta 948:970 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 6 36 theme alpha 1041:1045 arg1 beta 1056:1059 Fuc alpha 1-->2Gal beta 1037:1059 Fuc alpha 1-->2Gal beta 1037:1059 However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. 7763244 1 37 theme protein 217:223 arg1 structure 181:189 the N-linked oligosaccharide structure 152:189 the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP) 152:234 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 7 38 from heterogeneity 1219:1231 arg1 structure 1245:1253 the fine structure 1236:1253 the fine structure of its sugar chains 1236:1273 The present results suggest that the processing of beta APP may be regulated via the heterogeneity in the fine structure of its sugar chains. 7763244 7 39 theme beta 1185:1188 arg1 APP 1190:1192 beta APP 1185:1192 beta APP 1185:1192 The present results suggest that the processing of beta APP may be regulated via the heterogeneity in the fine structure of its sugar chains. 7763244 1 40 theme beta 226:229 arg1 protein 217:223 beta-amyloid precursor protein 194:223 beta-amyloid precursor protein (beta APP) 194:234 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 1 40 theme beta 226:229 arg1 APP 231:233 beta APP 226:233 beta APP 226:233 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 5 41 theme 1-->2Gal 930:937 arg1 beta 939:942 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta 898:942 beta 939:942 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 1 42 theme soluble 237:243 arg1 derivative 245:254 soluble derivative 237:254 soluble derivative of beta APP (APPs) 237:273 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 4 43 theme fucosylated 797:807 arg1 core 821:824 a fucosylated trimannosyl core 795:824 a fucosylated trimannosyl core 795:824 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 7 44 theme APP 1190:1192 arg1 processing 1171:1180 the processing 1167:1180 the processing of beta APP 1167:1192 The present results suggest that the processing of beta APP may be regulated via the heterogeneity in the fine structure of its sugar chains. 7763244 1 45 theme N-linked 156:163 arg1 structure 181:189 the N-linked oligosaccharide structure 152:189 the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP) 152:234 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 2 46 with APPs 375:378 arg1 weight 405:410 different molecular weight 385:410 different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) 385:454 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 2 46 with APPs 375:378 arg1 APPs 420:423 larger APPs 413:423 larger APPs 413:423 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 6 47 theme 2-->6Gal 1075:1082 arg1 beta 1084:1087 Sia alpha 2-->6Gal beta 1065:1087 Sia alpha 2-->6Gal beta 1065:1087 However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. 7763244 3 48 theme N-terminal 496:505 arg1 half 507:510 the N-terminal half 492:510 the N-terminal half of amyloid beta-protein 492:534 The antibody against the N-terminal half of amyloid beta-protein showed no immunoreactivity with S-APPs, suggesting extensive truncation at the carboxyl terminus. 7763244 4 49 gly fucosylated 797:807 arg1 core 821:824 a fucosylated trimannosyl core 795:824 a fucosylated trimannosyl core 795:824 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 4 50 theme complex 777:783 arg1 type 785:788 complex type 777:788 complex type 777:788 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 6 51 theme Sia 1065:1067 arg1 beta 1084:1087 Sia alpha 2-->6Gal beta 1065:1087 Sia alpha 2-->6Gal beta 1065:1087 However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. 7763244 4 52 dep bi- 757:759 arg1 type 785:788 complex type 777:788 complex type 777:788 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 4 53 theme GlcNAc 842:847 arg1 residue 849:855 a bisecting GlcNAc residue 830:855 a bisecting GlcNAc residue 830:855 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 6 54 theme beta 1056:1059 arg1 structures 1089:1098 Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures 1037:1098 Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures 1037:1098 However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. 7763244 0 55 theme beta 118:121 arg1 processing 127:136 beta APP processing 118:136 beta APP processing 118:136 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 1 56 theme glioma 348:353 arg1 cells 355:359 cDNA-transfected C6 glioma cells 328:359 cDNA-transfected C6 glioma cells 328:359 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 3 57 theme beta-protein 523:534 arg1 half 507:510 the N-terminal half 492:510 the N-terminal half of amyloid beta-protein 492:534 The antibody against the N-terminal half of amyloid beta-protein showed no immunoreactivity with S-APPs, suggesting extensive truncation at the carboxyl terminus. 7763244 1 58 theme beta-amyloid 194:205 arg1 protein 217:223 beta-amyloid precursor protein 194:223 beta-amyloid precursor protein (beta APP) 194:234 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 1 58 theme beta-amyloid 194:205 arg1 APP 231:233 beta APP 226:233 beta APP 226:233 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 5 59 theme beta 967:970 arg1 structures 972:981 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures 898:981 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures 898:981 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 7 60 theme sugar 1262:1266 arg1 chains 1268:1273 its sugar chains 1258:1273 its sugar chains 1258:1273 The present results suggest that the processing of beta APP may be regulated via the heterogeneity in the fine structure of its sugar chains. 7763244 7 61 theme present 1138:1144 arg1 results 1146:1152 The present results 1134:1152 The present results 1134:1152 The present results suggest that the processing of beta APP may be regulated via the heterogeneity in the fine structure of its sugar chains. 7763244 2 62 theme smaller 434:440 arg1 APPs 442:445 smaller APPs 434:445 smaller APPs 434:445 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 0 63 theme C6 73:74 arg1 cells 83:87 C6 glioma cells 73:87 C6 glioma cells 73:87 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 6 64 with reactivity 1110:1119 arg1 S-APPs 1126:1131 S-APPs 1126:1131 S-APPs 1126:1131 However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. 7763244 4 65 theme lectin 639:644 arg1 analysis 651:658 lectin blot analysis 639:658 lectin blot analysis 639:658 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 0 66 theme cells 83:87 arg1 protein 51:57 beta-amyloid precursor protein 28:57 beta-amyloid precursor protein (beta APP) of C6 glioma cells 28:87 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 0 66 theme cells 83:87 arg1 APP 65:67 beta APP 60:67 beta APP 60:67 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 4 67 theme oligosaccharide 696:710 arg1 structure 670:678 the main structure 661:678 the main structure of the N-linked oligosaccharide shared by L- and S-APPs 661:734 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 0 68 theme putative 90:97 arg1 role 110:113 putative regulatory role 90:113 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 0:137 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 1 69 theme beta 319:322 arg1 medium 309:314 the conditioned medium 293:314 the conditioned medium of beta APP cDNA-transfected C6 glioma cells 293:359 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 5 70 theme beta 902:905 arg1 beta 939:942 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta 898:942 beta 939:942 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 1 71 theme cDNA-transfected 328:343 arg1 cells 355:359 cDNA-transfected C6 glioma cells 328:359 cDNA-transfected C6 glioma cells 328:359 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 2 72 theme molecular 395:403 arg1 weight 405:410 different molecular weight 385:410 different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) 385:454 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 2 72 theme molecular 395:403 arg1 APPs 420:423 larger APPs 413:423 larger APPs 413:423 Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. 7763244 5 73 theme outer 990:994 arg1 chains 996:1001 its outer chains 986:1001 its outer chains 986:1001 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 0 74 theme beta-amyloid 28:39 arg1 protein 51:57 beta-amyloid precursor protein 28:57 beta-amyloid precursor protein (beta APP) of C6 glioma cells 28:87 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 0 74 theme beta-amyloid 28:39 arg1 APP 65:67 beta APP 60:67 beta APP 60:67 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 1 75 theme beta 259:262 arg1 APP 264:266 beta APP 259:266 beta APP (APPs) 259:273 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 1 75 theme beta 259:262 arg1 APPs 269:272 APPs 269:272 APPs 269:272 To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. 7763244 3 76 theme extensive 587:595 arg1 truncation 597:606 extensive truncation 587:606 extensive truncation at the carboxyl terminus 587:631 The antibody against the N-terminal half of amyloid beta-protein showed no immunoreactivity with S-APPs, suggesting extensive truncation at the carboxyl terminus. 7763244 0 77 theme protein 51:57 arg1 oligosaccharide 9:23 N-linked oligosaccharide 0:23 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 0:137 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 5 78 theme beta 939:942 arg1 structures 972:981 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures 898:981 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures 898:981 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 0 79 theme beta 60:63 arg1 protein 51:57 beta-amyloid precursor protein 28:57 beta-amyloid precursor protein (beta APP) of C6 glioma cells 28:87 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 0 79 theme beta 60:63 arg1 APP 65:67 beta APP 60:67 beta APP 60:67 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 7763244 5 80 theme Sia 948:950 arg1 beta 967:970 Sia alpha 2-->6Gal beta 948:970 Sia alpha 2-->6Gal beta 948:970 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 6 81 theme 1-->2Gal 1047:1054 arg1 beta 1056:1059 Fuc alpha 1-->2Gal beta 1037:1059 Fuc alpha 1-->2Gal beta 1037:1059 However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. 7763244 3 82 theme carboxyl 615:622 arg1 terminus 624:631 the carboxyl terminus 611:631 the carboxyl terminus 611:631 The antibody against the N-terminal half of amyloid beta-protein showed no immunoreactivity with S-APPs, suggesting extensive truncation at the carboxyl terminus. 7763244 6 83 theme Fuc 1037:1039 arg1 beta 1056:1059 Fuc alpha 1-->2Gal beta 1037:1059 Fuc alpha 1-->2Gal beta 1037:1059 However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. 7763244 5 84 theme alpha 924:928 arg1 beta 939:942 Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta 898:942 beta 939:942 Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. 7763244 4 85 link N-linked 687:694 arg1 oligosaccharide 696:710 the N-linked oligosaccharide 683:710 the N-linked oligosaccharide shared by L- and S-APPs 683:734 From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. 7763244 0 86 from role 110:113 arg1 processing 127:136 beta APP processing 118:136 beta APP processing 118:136 N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 8107688 10 0 from fraction 1791:1798 arg1 mucin 1815:1819 respiratory mucin 1803:1819 respiratory mucin 1803:1819 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 10 1 theme side 2066:2069 arg1 chains 2071:2076 the side chains 2062:2076 the side chains 2062:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 5 2 from weight 1049:1054 arg1 fractions 1091:1099 these fractions 1085:1099 these fractions 1085:1099 The average molecular weight of oligosaccharide chains in these fractions was between 27,000 and 40,000 daltons. 8107688 3 3 theme methylation 770:780 arg1 analysis 782:789 methylation analysis 770:789 methylation analysis 770:789 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 2 4 from chromatography 371:384 arg1 DEAE-Agarose 389:400 DEAE-Agarose 389:400 DEAE-Agarose 389:400 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 6 5 theme repeating 1240:1248 arg1 unit 1250:1253 the repeating unit 1236:1253 the repeating unit shown in the following oligosaccharide 1236:1292 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 3 6 theme sequential 816:825 arg1 digestion 839:847 sequential glycosidase digestion 816:847 sequential glycosidase digestion 816:847 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 10 7 theme weight 1902:1907 arg1 chains 1918:1923 high molecular weight branched chains 1887:1923 high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains 1887:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 1 8 theme patient 190:196 arg1 sputum 178:183 the sputum 174:183 the sputum of a patient with cystic fibrosis and blood group H determinant 174:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 9 9 theme sulfated 1672:1679 arg1 oligosaccharides 1681:1696 sulfated oligosaccharides 1672:1696 the high molecular weight sulfated oligosaccharides 1646:1696 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 10 10 theme high 1887:1890 arg1 weight 1902:1907 high molecular weight 1887:1907 high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains 1887:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 1 11 theme cystic 203:208 arg1 fibrosis 210:217 cystic fibrosis 203:217 cystic fibrosis 203:217 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 8 12 theme Several 1364:1370 arg1 chains 1380:1385 Several shorter chains 1364:1385 Several shorter chains which contain 2 to 3 sulfate esters 1364:1421 Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. 8107688 2 13 contain containing 417:426 arg1 fraction 408:415 a fraction 406:415 a fraction containing multisulfated chains 406:447 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 2 13 contain containing 417:426 arg2 chains 442:447 multisulfated chains 428:447 multisulfated chains 428:447 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 3 14 theme sugar 651:655 arg1 residues 657:664 160 to 200 sugar residues 640:664 160 to 200 sugar residues 640:664 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 4 15 theme residue 981:987 arg1 ratio 934:938 a ratio 932:938 a ratio of 1:2:2.1 and only one galactosaminitol residue for every 160- to 200 sugar residues 932:1024 Carbohydrate analysis yielded Fuc, Gal and GldNAc in a ratio of 1:2:2.1 and only one galactosaminitol residue for every 160- to 200 sugar residues. 8107688 1 16 theme oligosaccharide 127:141 arg1 chains 143:148 high molecular weight sulfated oligosaccharide chains 96:148 high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant 96:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 9 17 located found 1637:1641 arg2 those 1631:1635 those 1631:1635 those 1631:1635 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 9 17 located found 1637:1641 arg1 weight 1665:1670 the high molecular weight 1646:1670 the high molecular weight sulfated oligosaccharides 1646:1696 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 10 18 theme oligosaccharide 1953:1967 arg1 sequence 1969:1976 a repeating oligosaccharide sequence 1941:1976 a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains 1941:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 9 19 theme general 1610:1616 arg1 structure 1618:1626 the same general structure 1601:1626 the same general structure 1601:1626 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 9 20 theme same 1605:1608 arg1 structure 1618:1626 the same general structure 1601:1626 the same general structure 1601:1626 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 2 21 theme chains 553:558 arg1 amounts 531:537 small amounts 525:537 small amounts of sialylated chains 525:558 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 2 21 theme chains 553:558 arg1 chains 553:558 sialylated chains 542:558 sialylated chains 542:558 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 8 22 theme sulfate 1408:1414 arg1 esters 1416:1421 2 to 3 sulfate esters 1401:1421 2 to 3 sulfate esters 1401:1421 Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. 8107688 8 23 attach isolated 1433:1440 arg1 fraction 1482:1489 this multisulfated oligosaccharide fraction 1447:1489 this multisulfated oligosaccharide fraction 1447:1489 Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. 8107688 8 23 attach isolated 1433:1440 arg2 chains 1380:1385 Several shorter chains 1364:1385 Several shorter chains which contain 2 to 3 sulfate esters 1364:1421 Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. 8107688 7 24 contain contained 1338:1346 arg2 esters 1356:1361 sulfate esters 1348:1361 sulfate esters 1348:1361 Only one in about every 10 repeating units contained sulfate esters. 8107688 7 24 contain contained 1338:1346 arg1 one 1300:1302 one 1300:1302 one 1300:1302 Only one in about every 10 repeating units contained sulfate esters. 8107688 10 25 from chains 2071:2076 arg1 positions 2007:2015 the 6 positions 2001:2015 the 6 positions of galactose and possibly GlcNAc residues in the side chains 2001:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 4 26 theme sugar 1011:1015 arg1 residues 1017:1024 200 sugar residues 1007:1024 200 sugar residues 1007:1024 Carbohydrate analysis yielded Fuc, Gal and GldNAc in a ratio of 1:2:2.1 and only one galactosaminitol residue for every 160- to 200 sugar residues. 8107688 0 27 from Structures 0:9 arg1 trachea 49:55 human trachea 43:55 human trachea 43:55 Structures of sulfated oligosaccharides in human trachea mucin glycoproteins. 8107688 1 28 from mucins 153:158 arg1 structures 82:91 The structures 78:91 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant 78:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 5 29 theme average 1031:1037 arg1 weight 1049:1054 The average molecular weight 1027:1054 The average molecular weight of oligosaccharide chains in these fractions 1027:1099 The average molecular weight of oligosaccharide chains in these fractions was between 27,000 and 40,000 daltons. 8107688 2 30 theme multisulfated 428:440 arg1 chains 442:447 multisulfated chains 428:447 multisulfated chains 428:447 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 1 31 from chains 143:148 arg1 mucins 153:158 mucins 153:158 mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant 153:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 9 32 theme molecular 1655:1663 arg1 weight 1665:1670 the high molecular weight 1646:1670 the high molecular weight sulfated oligosaccharides 1646:1696 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 1 33 theme high 96:99 arg1 weight 111:116 high molecular weight 96:116 high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant 96:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 2 34 theme lectin 473:478 arg1 chromatography 489:502 lectin affinity chromatography 473:502 lectin affinity chromatography 473:502 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 10 35 theme repeating 1943:1951 arg1 sequence 1969:1976 a repeating oligosaccharide sequence 1941:1976 a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains 1941:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 8 36 theme oligosaccharide 1466:1480 arg1 fraction 1482:1489 this multisulfated oligosaccharide fraction 1447:1489 this multisulfated oligosaccharide fraction 1447:1489 Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. 8107688 0 37 theme sulfated 14:21 arg1 oligosaccharides 23:38 sulfated oligosaccharides 14:38 sulfated oligosaccharides 14:38 Structures of sulfated oligosaccharides in human trachea mucin glycoproteins. 8107688 10 38 theme cystic 1862:1867 arg1 fibrosis 1869:1876 cystic fibrosis 1862:1876 cystic fibrosis 1862:1876 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 1 39 theme weight 111:116 arg1 chains 143:148 high molecular weight sulfated oligosaccharide chains 96:148 high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant 96:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 2 40 theme small 525:529 arg1 amounts 531:537 small amounts 525:537 small amounts of sialylated chains 525:558 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 2 40 theme small 525:529 arg1 chains 553:558 sialylated chains 542:558 sialylated chains 542:558 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 3 41 theme BioGel 700:705 arg1 columns 712:718 BioGel P-10 columns 700:718 BioGel P-10 columns 700:718 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 10 42 theme oligosaccharide 1775:1789 arg1 fraction 1791:1798 a major sulfated oligosaccharide fraction 1758:1798 a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis 1758:1876 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 8 43 dep 3 1406:1406 arg1 to 1403:1404 to 1403:1404 to 1403:1404 Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. 8107688 2 44 theme exchange 362:369 arg1 chromatography 371:384 ion exchange chromatography 358:384 ion exchange chromatography on DEAE-Agarose 358:400 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 1 45 with patient 190:196 arg1 determinant 237:247 blood group H determinant 223:247 blood group H determinant 223:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 1 45 with patient 190:196 arg1 fibrosis 210:217 cystic fibrosis 203:217 cystic fibrosis 203:217 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 3 46 contain containing 603:612 arg2 chains 614:619 chains 614:619 chains 614:619 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 3 46 contain containing 603:612 arg1 fraction 594:601 A major sulfated oligosaccharide fraction 561:601 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues 561:664 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 3 47 theme individual 724:733 arg1 subfractions 735:746 individual subfractions 724:746 individual subfractions 724:746 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 1 48 theme blood 223:227 arg1 determinant 237:247 blood group H determinant 223:247 blood group H determinant 223:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 10 49 with patients 1848:1855 arg1 fibrosis 1869:1876 cystic fibrosis 1862:1876 cystic fibrosis 1862:1876 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 5 50 theme oligosaccharide 1059:1073 arg1 chains 1075:1080 oligosaccharide chains 1059:1080 oligosaccharide chains 1059:1080 The average molecular weight of oligosaccharide chains in these fractions was between 27,000 and 40,000 daltons. 8107688 6 51 theme weight 1193:1198 arg1 chains 1200:1205 these high molecular weight chains 1172:1205 these high molecular weight chains 1172:1205 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 3 52 theme major 563:567 arg1 fraction 594:601 A major sulfated oligosaccharide fraction 561:601 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues 561:664 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 1 53 theme H 235:235 arg1 determinant 237:247 blood group H determinant 223:247 blood group H determinant 223:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 6 54 theme high 1178:1181 arg1 weight 1193:1198 high molecular weight 1178:1198 these high molecular weight chains 1172:1205 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 1 55 from structures 82:91 arg1 mucins 153:158 mucins 153:158 mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant 153:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 7 56 theme repeating 1322:1330 arg1 units 1332:1336 about every 10 repeating units 1307:1336 about every 10 repeating units 1307:1336 Only one in about every 10 repeating units contained sulfate esters. 8107688 10 57 theme galactose 2020:2028 arg1 positions 2007:2015 the 6 positions 2001:2015 the 6 positions of galactose and possibly GlcNAc residues in the side chains 2001:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 4 58 theme 1:2:2.1 943:949 arg1 ratio 934:938 a ratio 932:938 a ratio of 1:2:2.1 and only one galactosaminitol residue for every 160- to 200 sugar residues 932:1024 Carbohydrate analysis yielded Fuc, Gal and GldNAc in a ratio of 1:2:2.1 and only one galactosaminitol residue for every 160- to 200 sugar residues. 8107688 9 59 dep weight 1665:1670 arg1 oligosaccharides 1681:1696 sulfated oligosaccharides 1672:1696 the high molecular weight sulfated oligosaccharides 1646:1696 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 3 60 theme periodate 792:800 arg1 oxidation 802:810 periodate oxidation 792:810 periodate oxidation 792:810 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 3 61 theme oligosaccharide 578:592 arg1 fraction 594:601 A major sulfated oligosaccharide fraction 561:601 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues 561:664 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 10 62 from positions 2007:2015 arg1 chains 2071:2076 the side chains 2062:2076 the side chains 2062:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 6 63 theme unit 1250:1253 arg1 amounts 1225:1231 varying amounts 1217:1231 varying amounts of the repeating unit shown in the following oligosaccharide 1217:1292 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 6 63 theme unit 1250:1253 arg1 unit 1250:1253 the repeating unit 1236:1253 the repeating unit shown in the following oligosaccharide 1236:1292 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 10 64 theme residues 2050:2057 arg1 positions 2007:2015 the 6 positions 2001:2015 the 6 positions of galactose and possibly GlcNAc residues in the side chains 2001:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 10 65 theme branched 1909:1916 arg1 chains 1918:1923 high molecular weight branched chains 1887:1923 high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains 1887:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 3 66 dep 200 647:649 arg1 to 644:645 to 644:645 to 644:645 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 10 67 from galactose 2020:2028 arg1 chains 2071:2076 the side chains 2062:2076 the side chains 2062:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 3 68 theme glycosidase 827:837 arg1 digestion 839:847 sequential glycosidase digestion 816:847 sequential glycosidase digestion 816:847 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 2 69 theme alkaline 319:326 arg1 borohydride 328:338 alkaline borohydride 319:338 alkaline borohydride 319:338 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 9 70 theme lower 1566:1570 arg1 they 1557:1560 they 1557:1560 they 1557:1560 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 9 70 theme lower 1566:1570 arg1 chains 1589:1594 lower molecular weight chains 1566:1594 lower molecular weight chains with the same general structure 1566:1626 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 10 71 theme studies 1740:1746 arg1 results 1723:1729 the results 1719:1729 the results of these studies 1719:1746 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 9 72 theme weight 1582:1587 arg1 they 1557:1560 they 1557:1560 they 1557:1560 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 9 72 theme weight 1582:1587 arg1 chains 1589:1594 lower molecular weight chains 1566:1594 lower molecular weight chains with the same general structure 1566:1626 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 10 73 from residues 2050:2057 arg1 chains 2071:2076 the side chains 2062:2076 the side chains 2062:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 6 74 contain contained 1207:1215 arg1 chains 1200:1205 these high molecular weight chains 1172:1205 these high molecular weight chains 1172:1205 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 6 74 contain contained 1207:1215 arg2 unit 1250:1253 the repeating unit 1236:1253 the repeating unit shown in the following oligosaccharide 1236:1292 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 6 74 contain contained 1207:1215 arg2 amounts 1225:1231 varying amounts 1217:1231 varying amounts of the repeating unit shown in the following oligosaccharide 1217:1292 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 1 75 theme sulfated 118:125 arg1 chains 143:148 high molecular weight sulfated oligosaccharide chains 96:148 high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant 96:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 10 76 with sequence 1969:1976 arg1 sulfate 1983:1989 sulfate 1983:1989 sulfate 1983:1989 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 8 77 contain contain 1393:1399 arg2 esters 1416:1421 2 to 3 sulfate esters 1401:1421 2 to 3 sulfate esters 1401:1421 Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. 8107688 8 77 contain contain 1393:1399 arg1 chains 1380:1385 Several shorter chains 1364:1385 Several shorter chains which contain 2 to 3 sulfate esters 1364:1421 Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. 8107688 7 78 from one 1300:1302 arg1 units 1332:1336 about every 10 repeating units 1307:1336 about every 10 repeating units 1307:1336 Only one in about every 10 repeating units contained sulfate esters. 8107688 2 79 theme Reduced 267:273 arg1 oligosaccharides 275:290 Reduced oligosaccharides 267:290 Reduced oligosaccharides released by treatment with alkaline borohydride 267:338 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 1 80 theme chains 143:148 arg1 structures 82:91 The structures 78:91 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant 78:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 10 81 theme molecular 1892:1900 arg1 weight 1902:1907 high molecular weight 1887:1907 high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains 1887:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 4 82 theme galactosaminitol 964:979 arg1 residue 981:987 only one galactosaminitol residue 955:987 only one galactosaminitol residue for every 160- 955:1002 Carbohydrate analysis yielded Fuc, Gal and GldNAc in a ratio of 1:2:2.1 and only one galactosaminitol residue for every 160- to 200 sugar residues. 8107688 8 83 dep Several 1364:1370 arg1 shorter 1372:1378 shorter 1372:1378 shorter 1372:1378 Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. 8107688 3 84 theme residues 657:664 arg1 average 629:635 an average 626:635 an average of 160 to 200 sugar residues 626:664 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 2 85 with treatment 304:312 arg1 borohydride 328:338 alkaline borohydride 319:338 alkaline borohydride 319:338 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 2 86 theme sialylated 542:551 arg1 chains 553:558 sialylated chains 542:558 sialylated chains 542:558 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 6 87 theme following 1268:1276 arg1 oligosaccharide 1278:1292 the following oligosaccharide 1264:1292 the following oligosaccharide 1264:1292 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 10 88 attach linked 1991:1996 arg2 sequence 1969:1976 a repeating oligosaccharide sequence 1941:1976 a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains 1941:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 10 88 attach linked 1991:1996 arg1 positions 2007:2015 the 6 positions 2001:2015 the 6 positions of galactose and possibly GlcNAc residues in the side chains 2001:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 10 89 contain contains 1878:1885 arg2 chains 1918:1923 high molecular weight branched chains 1887:1923 high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains 1887:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 10 89 contain contains 1878:1885 arg1 fraction 1791:1798 a major sulfated oligosaccharide fraction 1758:1798 a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis 1758:1876 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 0 90 gly glycoproteins 63:75 arg1 glycoproteins 63:75 glycoproteins 63:75 glycoproteins 63:75 Structures of sulfated oligosaccharides in human trachea mucin glycoproteins. 8107688 9 91 theme molecular 1572:1580 arg1 they 1557:1560 they 1557:1560 they 1557:1560 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 9 91 theme molecular 1572:1580 arg1 chains 1589:1594 lower molecular weight chains 1566:1594 lower molecular weight chains with the same general structure 1566:1626 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 9 92 theme high 1650:1653 arg1 weight 1665:1670 the high molecular weight 1646:1670 the high molecular weight sulfated oligosaccharides 1646:1696 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 2 93 gly sialylated 542:551 arg1 chains 553:558 sialylated chains 542:558 sialylated chains 542:558 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 6 94 theme Structural 1140:1149 arg1 analysis 1151:1158 Structural analysis 1140:1158 Structural analysis 1140:1158 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 2 95 theme affinity 480:487 arg1 chromatography 489:502 lectin affinity chromatography 473:502 lectin affinity chromatography 473:502 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 0 96 theme oligosaccharides 23:38 arg1 Structures 0:9 Structures 0:9 Structures of sulfated oligosaccharides in human trachea 0:55 Structures of sulfated oligosaccharides in human trachea mucin glycoproteins. 8107688 1 97 theme molecular 101:109 arg1 weight 111:116 high molecular weight 96:116 high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant 96:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 5 98 theme molecular 1039:1047 arg1 weight 1049:1054 The average molecular weight 1027:1054 The average molecular weight of oligosaccharide chains in these fractions 1027:1099 The average molecular weight of oligosaccharide chains in these fractions was between 27,000 and 40,000 daltons. 8107688 8 99 theme multisulfated 1452:1464 arg1 fraction 1482:1489 this multisulfated oligosaccharide fraction 1447:1489 this multisulfated oligosaccharide fraction 1447:1489 Several shorter chains which contain 2 to 3 sulfate esters were also isolated from this multisulfated oligosaccharide fraction. 8107688 10 100 theme patients 1848:1855 arg1 mucus 1839:1843 the mucus 1835:1843 the mucus of patients with cystic fibrosis 1835:1876 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 0 101 theme human 43:47 arg1 trachea 49:55 human trachea 43:55 human trachea 43:55 Structures of sulfated oligosaccharides in human trachea mucin glycoproteins. 8107688 10 102 theme major 1760:1764 arg1 fraction 1791:1798 a major sulfated oligosaccharide fraction 1758:1798 a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis 1758:1876 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 3 103 theme gel 682:684 arg1 filtration 686:695 gel filtration 682:695 gel filtration 682:695 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 10 104 theme sulfated 1766:1773 arg1 fraction 1791:1798 a major sulfated oligosaccharide fraction 1758:1798 a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis 1758:1876 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 6 105 theme varying 1217:1223 arg1 amounts 1225:1231 varying amounts 1217:1231 varying amounts of the repeating unit shown in the following oligosaccharide 1217:1292 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 6 105 theme varying 1217:1223 arg1 unit 1250:1253 the repeating unit 1236:1253 the repeating unit shown in the following oligosaccharide 1236:1292 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 9 106 with chains 1589:1594 arg1 structure 1618:1626 the same general structure 1601:1626 the same general structure 1601:1626 The structures proposed for these oligosaccharides indicate that they are lower molecular weight chains with the same general structure as those found in the high molecular weight sulfated oligosaccharides. 8107688 2 107 theme ion 358:360 arg1 chromatography 371:384 ion exchange chromatography 358:384 ion exchange chromatography on DEAE-Agarose 358:400 Reduced oligosaccharides released by treatment with alkaline borohydride were separated by ion exchange chromatography on DEAE-Agarose and a fraction containing multisulfated chains was further purified by lectin affinity chromatography to completely remove small amounts of sialylated chains. 8107688 7 108 theme sulfate 1348:1354 arg1 esters 1356:1361 sulfate esters 1348:1361 sulfate esters 1348:1361 Only one in about every 10 repeating units contained sulfate esters. 8107688 3 109 theme P-10 707:710 arg1 columns 712:718 BioGel P-10 columns 700:718 BioGel P-10 columns 700:718 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 8107688 10 110 theme respiratory 1803:1813 arg1 mucin 1815:1819 respiratory mucin 1803:1819 respiratory mucin 1803:1819 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 1 111 theme group 229:233 arg1 determinant 237:247 blood group H determinant 223:247 blood group H determinant 223:247 The structures of high molecular weight sulfated oligosaccharide chains in mucins purified from the sputum of a patient with cystic fibrosis and blood group H determinant were established. 8107688 5 112 theme chains 1075:1080 arg1 weight 1049:1054 The average molecular weight 1027:1054 The average molecular weight of oligosaccharide chains in these fractions 1027:1099 The average molecular weight of oligosaccharide chains in these fractions was between 27,000 and 40,000 daltons. 8107688 6 113 theme molecular 1183:1191 arg1 weight 1193:1198 high molecular weight 1178:1198 these high molecular weight chains 1172:1205 Structural analysis showed that these high molecular weight chains contained varying amounts of the repeating unit shown in the following oligosaccharide. 8107688 10 114 theme GlcNAc 2043:2048 arg1 residues 2050:2057 GlcNAc residues 2043:2057 GlcNAc residues in the side chains 2043:2076 Taken collectively, the results of these studies show that a major sulfated oligosaccharide fraction in respiratory mucin purified from the mucus of patients with cystic fibrosis contains high molecular weight branched chains that consist of a repeating oligosaccharide sequence with sulfate linked to the 6 positions of galactose and possibly GlcNAc residues in the side chains. 8107688 4 115 theme Carbohydrate 879:890 arg1 analysis 892:899 Carbohydrate analysis 879:899 Carbohydrate analysis 879:899 Carbohydrate analysis yielded Fuc, Gal and GldNAc in a ratio of 1:2:2.1 and only one galactosaminitol residue for every 160- to 200 sugar residues. 8107688 3 116 theme sulfated 569:576 arg1 fraction 594:601 A major sulfated oligosaccharide fraction 561:601 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues 561:664 A major sulfated oligosaccharide fraction containing chains with an average of 160 to 200 sugar residues was isolated by gel filtration on BioGel P-10 columns and individual subfractions were characterized by methylation analysis, periodate oxidation and sequential glycosidase digestion before and after desulfation. 7785764 4 0 from chromatography 677:690 arg1 column 715:720 a diethylaminoethyl column 695:720 a diethylaminoethyl column according to the sialic acid content 695:757 The mixture of PA-oligosaccharides was separated by high-performance liquid chromatography on a diethylaminoethyl column according to the sialic acid content. 7785764 8 1 theme unique 1138:1143 arg1 coordinates 1152:1162 coordinates 1152:1162 coordinates 1152:1162 The elution volumes from these two columns (ODS and amide) provide a unique set of coordinates. 7785764 8 1 theme unique 1138:1143 arg1 set 1145:1147 a unique set 1136:1147 a unique set of coordinates 1136:1162 The elution volumes from these two columns (ODS and amide) provide a unique set of coordinates. 7785764 7 2 theme elution 1008:1014 arg1 volume 1016:1021 Each peak's elution volume 996:1021 Each peak's elution volume 996:1021 Each peak's elution volume was recorded as a glucose unit on the Y-axis. 7785764 7 2 theme elution 1008:1014 arg1 unit 1049:1052 a glucose unit 1039:1052 a glucose unit on the Y-axis 1039:1066 Each peak's elution volume was recorded as a glucose unit on the Y-axis. 7785764 0 3 theme serum 84:88 arg1 glycoproteins 90:102 human serum glycoproteins 78:102 human serum glycoproteins using three kinds of high-performance liquid chromatography 78:162 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 6 4 theme separated 936:944 arg1 oligosaccharides 946:961 the separated oligosaccharides 932:961 the separated oligosaccharides 932:961 Then, each of the separated oligosaccharides was applied to the amide column. 7785764 9 5 theme fraction 1210:1217 arg1 structure 1169:1177 The structure 1165:1177 The structure of each sialyl oligosaccharide fraction 1165:1217 The structure of each sialyl oligosaccharide fraction was analyzed by the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides. 7785764 10 6 theme exoglycosidase 1361:1374 arg1 digestion 1376:1384 exoglycosidase digestion 1361:1384 exoglycosidase digestion 1361:1384 This was combined with exoglycosidase digestion and high-resolution proton NMR measurement. 7785764 1 7 theme neutral 185:191 arg1 oligosaccharides 213:228 neutral and sialyl N-linked oligosaccharides 185:228 oligosaccharides 213:228 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 9 8 theme neutral 1312:1318 arg1 oligosaccharides 1320:1335 neutral oligosaccharides 1312:1335 neutral oligosaccharides 1312:1335 The structure of each sialyl oligosaccharide fraction was analyzed by the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides. 7785764 3 9 theme reagent 571:577 arg1 PA 596:597 PA 596:597 PA 596:597 The reducing ends of the oligosaccharides were derivatized with the fluorescent reagent 2-aminopyridine (PA). 7785764 3 9 theme reagent 571:577 arg1 2-aminopyridine 579:593 the fluorescent reagent 2-aminopyridine 555:593 the fluorescent reagent 2-aminopyridine (PA) 555:598 The reducing ends of the oligosaccharides were derivatized with the fluorescent reagent 2-aminopyridine (PA). 7785764 4 10 theme high-performance 653:668 arg1 chromatography 677:690 high-performance liquid chromatography 653:690 high-performance liquid chromatography on a diethylaminoethyl column according to the sialic acid content 653:757 The mixture of PA-oligosaccharides was separated by high-performance liquid chromatography on a diethylaminoethyl column according to the sialic acid content. 7785764 5 11 theme octadecylsilyl 807:820 arg1 column 828:833 an octadecylsilyl (ODS) column 804:833 an octadecylsilyl (ODS) column 804:833 Each fraction separated was then applied on an octadecylsilyl (ODS) column, and the elution volume of each peak was recorded as a glucose unit on the X-axis. 7785764 4 12 theme diethylaminoethyl 697:713 arg1 column 715:720 a diethylaminoethyl column 695:720 a diethylaminoethyl column according to the sialic acid content 695:757 The mixture of PA-oligosaccharides was separated by high-performance liquid chromatography on a diethylaminoethyl column according to the sialic acid content. 7785764 5 13 from unit 898:901 arg1 X-axis 910:915 the X-axis 906:915 the X-axis 906:915 Each fraction separated was then applied on an octadecylsilyl (ODS) column, and the elution volume of each peak was recorded as a glucose unit on the X-axis. 7785764 11 14 dep neutral 1439:1445 arg1 oligosaccharides 1502:1517 oligosaccharides 1502:1517 oligosaccharides 1502:1517 Fourteen neutral, eight mon-sialyl, four di-sialyl, and five tri-sialyl oligosaccharides were isolated from human serum and their structures were characterized. 7785764 1 15 theme HPLC 299:302 arg1 columns 304:310 HPLC columns 299:310 HPLC columns 299:310 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 2 16 gly glycopeptides 412:424 arg2 glycopeptides 412:424 chymotrypsin- and trypsin-digested glycopeptides 377:424 chymotrypsin- and trypsin-digested glycopeptides of human serum 377:439 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 2 16 gly glycopeptides 412:424 arg1 serum 435:439 human serum 429:439 human serum 429:439 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 1 17 link N-linked 204:211 arg1 oligosaccharides 213:228 neutral and sialyl N-linked oligosaccharides 185:228 oligosaccharides 213:228 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 1 18 from distribution 169:180 arg1 glycoproteins 247:259 human serum glycoproteins 235:259 human serum glycoproteins 235:259 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 4 19 theme sialic 739:744 arg1 content 751:757 the sialic acid content 735:757 the sialic acid content 735:757 The mixture of PA-oligosaccharides was separated by high-performance liquid chromatography on a diethylaminoethyl column according to the sialic acid content. 7785764 5 20 theme ODS 823:825 arg1 column 828:833 an octadecylsilyl (ODS) column 804:833 an octadecylsilyl (ODS) column 804:833 Each fraction separated was then applied on an octadecylsilyl (ODS) column, and the elution volume of each peak was recorded as a glucose unit on the X-axis. 7785764 2 21 attach released 363:370 arg1 glycopeptides 412:424 chymotrypsin- and trypsin-digested glycopeptides 377:424 chymotrypsin- and trypsin-digested glycopeptides of human serum 377:439 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 2 21 attach released 363:370 arg2 oligosaccharides 341:356 N-linked oligosaccharides 332:356 N-linked oligosaccharides 332:356 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 8 22 dep columns 1104:1110 arg1 ODS 1113:1115 ODS 1113:1115 ODS 1113:1115 The elution volumes from these two columns (ODS and amide) provide a unique set of coordinates. 7785764 8 22 dep columns 1104:1110 arg1 columns 1104:1110 these two columns 1094:1110 these two columns (ODS and amide) 1094:1126 The elution volumes from these two columns (ODS and amide) provide a unique set of coordinates. 7785764 8 22 dep columns 1104:1110 arg1 amide 1121:1125 amide 1121:1125 amide 1121:1125 The elution volumes from these two columns (ODS and amide) provide a unique set of coordinates. 7785764 9 23 theme sialyl 1187:1192 arg1 fraction 1210:1217 each sialyl oligosaccharide fraction 1182:1217 each sialyl oligosaccharide fraction 1182:1217 The structure of each sialyl oligosaccharide fraction was analyzed by the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides. 7785764 0 24 gly glycoproteins 90:102 arg1 glycoproteins 90:102 human serum glycoproteins 78:102 human serum glycoproteins using three kinds of high-performance liquid chromatography 78:162 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 1 25 theme sialyl 197:202 arg1 oligosaccharides 213:228 neutral and sialyl N-linked oligosaccharides 185:228 oligosaccharides 213:228 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 11 26 attach isolated 1524:1531 arg2 mon-sialyl 1454:1463 mon-sialyl 1454:1463 mon-sialyl 1454:1463 Fourteen neutral, eight mon-sialyl, four di-sialyl, and five tri-sialyl oligosaccharides were isolated from human serum and their structures were characterized. 7785764 11 26 attach isolated 1524:1531 arg1 serum 1544:1548 human serum 1538:1548 human serum 1538:1548 Fourteen neutral, eight mon-sialyl, four di-sialyl, and five tri-sialyl oligosaccharides were isolated from human serum and their structures were characterized. 7785764 11 26 attach isolated 1524:1531 arg2 neutral 1439:1445 neutral 1439:1445 neutral 1439:1445 Fourteen neutral, eight mon-sialyl, four di-sialyl, and five tri-sialyl oligosaccharides were isolated from human serum and their structures were characterized. 7785764 11 26 attach isolated 1524:1531 arg2 tri-sialyl 1491:1500 tri-sialyl 1491:1500 tri-sialyl 1491:1500 Fourteen neutral, eight mon-sialyl, four di-sialyl, and five tri-sialyl oligosaccharides were isolated from human serum and their structures were characterized. 7785764 11 26 attach isolated 1524:1531 arg2 di-sialyl 1471:1479 di-sialyl 1471:1479 di-sialyl 1471:1479 Fourteen neutral, eight mon-sialyl, four di-sialyl, and five tri-sialyl oligosaccharides were isolated from human serum and their structures were characterized. 7785764 1 27 gly glycoproteins 247:259 arg1 glycoproteins 247:259 human serum glycoproteins 235:259 human serum glycoproteins 235:259 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 9 28 theme oligosaccharide 1194:1208 arg1 fraction 1210:1217 each sialyl oligosaccharide fraction 1182:1217 each sialyl oligosaccharide fraction 1182:1217 The structure of each sialyl oligosaccharide fraction was analyzed by the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides. 7785764 1 29 theme N-linked 204:211 arg1 oligosaccharides 213:228 neutral and sialyl N-linked oligosaccharides 185:228 oligosaccharides 213:228 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 5 30 theme peak 867:870 arg1 volume 852:857 the elution volume 840:857 the elution volume of each peak 840:870 Each fraction separated was then applied on an octadecylsilyl (ODS) column, and the elution volume of each peak was recorded as a glucose unit on the X-axis. 7785764 5 30 theme peak 867:870 arg1 unit 898:901 a glucose unit 888:901 a glucose unit on the X-axis 888:915 Each fraction separated was then applied on an octadecylsilyl (ODS) column, and the elution volume of each peak was recorded as a glucose unit on the X-axis. 7785764 1 31 theme columns 304:310 arg1 kinds 290:294 three kinds 284:294 three kinds of HPLC columns as described below 284:329 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 8 32 theme elution 1073:1079 arg1 volumes 1081:1087 The elution volumes 1069:1087 The elution volumes from these two columns (ODS and amide) 1069:1126 The elution volumes from these two columns (ODS and amide) provide a unique set of coordinates. 7785764 0 33 link N-linked 37:44 arg1 structures 62:71 neutral and sialyl N-linked oligosaccharide structures 18:71 neutral and sialyl N-linked oligosaccharide structures 18:71 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 2 34 dep digestion 480:488 arg1 means 444:448 means 444:448 means 444:448 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 1 35 theme oligosaccharides 213:228 arg1 distribution 169:180 The distribution 165:180 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins 165:259 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 5 36 theme glucose 890:896 arg1 volume 852:857 the elution volume 840:857 the elution volume of each peak 840:870 Each fraction separated was then applied on an octadecylsilyl (ODS) column, and the elution volume of each peak was recorded as a glucose unit on the X-axis. 7785764 5 36 theme glucose 890:896 arg1 unit 898:901 a glucose unit 888:901 a glucose unit on the X-axis 888:915 Each fraction separated was then applied on an octadecylsilyl (ODS) column, and the elution volume of each peak was recorded as a glucose unit on the X-axis. 7785764 8 37 theme coordinates 1152:1162 arg1 coordinates 1152:1162 coordinates 1152:1162 coordinates 1152:1162 The elution volumes from these two columns (ODS and amide) provide a unique set of coordinates. 7785764 8 37 theme coordinates 1152:1162 arg1 set 1145:1147 a unique set 1136:1147 a unique set of coordinates 1136:1162 The elution volumes from these two columns (ODS and amide) provide a unique set of coordinates. 7785764 0 38 theme liquid 142:147 arg1 chromatography 149:162 high-performance liquid chromatography 125:162 high-performance liquid chromatography 125:162 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 2 39 theme N-linked 332:339 arg1 oligosaccharides 341:356 N-linked oligosaccharides 332:356 N-linked oligosaccharides 332:356 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 7 40 theme glucose 1041:1047 arg1 volume 1016:1021 Each peak's elution volume 996:1021 Each peak's elution volume 996:1021 Each peak's elution volume was recorded as a glucose unit on the Y-axis. 7785764 7 40 theme glucose 1041:1047 arg1 unit 1049:1052 a glucose unit 1039:1052 a glucose unit on the Y-axis 1039:1066 Each peak's elution volume was recorded as a glucose unit on the Y-axis. 7785764 0 41 theme neutral 18:24 arg1 structures 62:71 neutral and sialyl N-linked oligosaccharide structures 18:71 neutral and sialyl N-linked oligosaccharide structures 18:71 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 4 42 theme PA-oligosaccharides 616:634 arg1 mixture 605:611 The mixture 601:611 The mixture of PA-oligosaccharides 601:634 The mixture of PA-oligosaccharides was separated by high-performance liquid chromatography on a diethylaminoethyl column according to the sialic acid content. 7785764 0 43 theme high-performance 125:140 arg1 chromatography 149:162 high-performance liquid chromatography 125:162 high-performance liquid chromatography 125:162 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 0 44 from glycoproteins 90:102 arg1 Identification 0:13 Identification 0:13 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 0:163 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 2 45 theme trypsin-digested 395:410 arg1 glycopeptides 412:424 chymotrypsin- and trypsin-digested glycopeptides 377:424 chymotrypsin- and trypsin-digested glycopeptides of human serum 377:439 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 1 46 theme human 235:239 arg1 glycoproteins 247:259 human serum glycoproteins 235:259 human serum glycoproteins 235:259 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 0 47 theme N-linked 37:44 arg1 structures 62:71 neutral and sialyl N-linked oligosaccharide structures 18:71 neutral and sialyl N-linked oligosaccharide structures 18:71 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 3 48 theme reducing 495:502 arg1 ends 504:507 The reducing ends 491:507 The reducing ends of the oligosaccharides 491:531 The reducing ends of the oligosaccharides were derivatized with the fluorescent reagent 2-aminopyridine (PA). 7785764 2 49 theme serum 435:439 arg1 glycopeptides 412:424 chymotrypsin- and trypsin-digested glycopeptides 377:424 chymotrypsin- and trypsin-digested glycopeptides of human serum 377:439 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 1 50 theme serum 241:245 arg1 glycoproteins 247:259 human serum glycoproteins 235:259 human serum glycoproteins 235:259 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 0 51 theme sialyl 30:35 arg1 structures 62:71 neutral and sialyl N-linked oligosaccharide structures 18:71 neutral and sialyl N-linked oligosaccharide structures 18:71 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 2 52 link N-linked 332:339 arg1 oligosaccharides 341:356 N-linked oligosaccharides 332:356 N-linked oligosaccharides 332:356 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 0 53 theme chromatography 149:162 arg1 kinds 116:120 three kinds 110:120 three kinds of high-performance liquid chromatography 110:162 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 2 54 theme glycoamidase 453:464 arg1 digestion 480:488 glycoamidase (from almond) digestion 453:488 glycoamidase (from almond) digestion 453:488 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 0 55 theme structures 62:71 arg1 Identification 0:13 Identification 0:13 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 0:163 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 6 56 theme amide 982:986 arg1 column 988:993 the amide column 978:993 the amide column 978:993 Then, each of the separated oligosaccharides was applied to the amide column. 7785764 9 57 theme same 1239:1242 arg1 technique 1274:1282 the same two-dimensional sugar-mapping technique 1235:1282 the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides 1235:1335 The structure of each sialyl oligosaccharide fraction was analyzed by the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides. 7785764 1 58 from glycoproteins 247:259 arg1 distribution 169:180 The distribution 165:180 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins 165:259 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 1 58 from glycoproteins 247:259 arg1 oligosaccharides 213:228 neutral and sialyl N-linked oligosaccharides 185:228 oligosaccharides 213:228 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 0 59 theme oligosaccharide 46:60 arg1 structures 62:71 neutral and sialyl N-linked oligosaccharide structures 18:71 neutral and sialyl N-linked oligosaccharide structures 18:71 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 9 60 theme two-dimensional 1244:1258 arg1 technique 1274:1282 the same two-dimensional sugar-mapping technique 1235:1282 the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides 1235:1335 The structure of each sialyl oligosaccharide fraction was analyzed by the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides. 7785764 9 61 theme sugar-mapping 1260:1272 arg1 technique 1274:1282 the same two-dimensional sugar-mapping technique 1235:1282 the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides 1235:1335 The structure of each sialyl oligosaccharide fraction was analyzed by the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides. 7785764 3 62 theme fluorescent 559:569 arg1 PA 596:597 PA 596:597 PA 596:597 The reducing ends of the oligosaccharides were derivatized with the fluorescent reagent 2-aminopyridine (PA). 7785764 3 62 theme fluorescent 559:569 arg1 2-aminopyridine 579:593 the fluorescent reagent 2-aminopyridine 555:593 the fluorescent reagent 2-aminopyridine (PA) 555:598 The reducing ends of the oligosaccharides were derivatized with the fluorescent reagent 2-aminopyridine (PA). 7785764 2 63 theme chymotrypsin- 377:389 arg1 glycopeptides 412:424 chymotrypsin- and trypsin-digested glycopeptides 377:424 chymotrypsin- and trypsin-digested glycopeptides of human serum 377:439 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 11 64 theme human 1538:1542 arg1 serum 1544:1548 human serum 1538:1548 human serum 1538:1548 Fourteen neutral, eight mon-sialyl, four di-sialyl, and five tri-sialyl oligosaccharides were isolated from human serum and their structures were characterized. 7785764 4 65 theme acid 746:749 arg1 content 751:757 the sialic acid content 735:757 the sialic acid content 735:757 The mixture of PA-oligosaccharides was separated by high-performance liquid chromatography on a diethylaminoethyl column according to the sialic acid content. 7785764 3 66 theme oligosaccharides 516:531 arg1 ends 504:507 The reducing ends 491:507 The reducing ends of the oligosaccharides 491:531 The reducing ends of the oligosaccharides were derivatized with the fluorescent reagent 2-aminopyridine (PA). 7785764 10 67 theme high-resolution 1390:1404 arg1 measurement 1417:1427 high-resolution proton NMR measurement 1390:1427 high-resolution proton NMR measurement 1390:1427 This was combined with exoglycosidase digestion and high-resolution proton NMR measurement. 7785764 7 68 from unit 1049:1052 arg1 Y-axis 1061:1066 the Y-axis 1057:1066 the Y-axis 1057:1066 Each peak's elution volume was recorded as a glucose unit on the Y-axis. 7785764 10 69 theme NMR 1413:1415 arg1 measurement 1417:1427 high-resolution proton NMR measurement 1390:1427 high-resolution proton NMR measurement 1390:1427 This was combined with exoglycosidase digestion and high-resolution proton NMR measurement. 7785764 4 70 theme liquid 670:675 arg1 chromatography 677:690 high-performance liquid chromatography 653:690 high-performance liquid chromatography on a diethylaminoethyl column according to the sialic acid content 653:757 The mixture of PA-oligosaccharides was separated by high-performance liquid chromatography on a diethylaminoethyl column according to the sialic acid content. 7785764 0 71 theme human 78:82 arg1 glycoproteins 90:102 human serum glycoproteins 78:102 human serum glycoproteins using three kinds of high-performance liquid chromatography 78:162 Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. 7785764 1 72 dep kinds 290:294 arg1 described 315:323 described 315:323 described below 315:329 The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. 7785764 10 73 theme proton 1406:1411 arg1 measurement 1417:1427 high-resolution proton NMR measurement 1390:1427 high-resolution proton NMR measurement 1390:1427 This was combined with exoglycosidase digestion and high-resolution proton NMR measurement. 7785764 2 74 theme human 429:433 arg1 serum 435:439 human serum 429:439 human serum 429:439 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 5 75 theme elution 844:850 arg1 volume 852:857 the elution volume 840:857 the elution volume of each peak 840:870 Each fraction separated was then applied on an octadecylsilyl (ODS) column, and the elution volume of each peak was recorded as a glucose unit on the X-axis. 7785764 5 75 theme elution 844:850 arg1 unit 898:901 a glucose unit 888:901 a glucose unit on the X-axis 888:915 Each fraction separated was then applied on an octadecylsilyl (ODS) column, and the elution volume of each peak was recorded as a glucose unit on the X-axis. 7785764 2 76 from almond 472:477 arg1 glycoamidase 453:464 glycoamidase 453:464 glycoamidase (from almond) digestion 453:488 N-linked oligosaccharides were released from chymotrypsin- and trypsin-digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. 7785764 8 77 from columns 1104:1110 arg1 volumes 1081:1087 The elution volumes 1069:1087 The elution volumes from these two columns (ODS and amide) 1069:1126 The elution volumes from these two columns (ODS and amide) provide a unique set of coordinates. 3665919 0 0 theme blood 94:98 arg1 O 106:106 blood group O 94:106 blood group O 94:106 Structure of sialyl-oligosaccharides isolated from bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis. 3665919 0 0 theme blood 94:98 arg1 patients 84:91 patients 84:91 patients (blood group O) suffering from cystic fibrosis 84:138 Structure of sialyl-oligosaccharides isolated from bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis. 3665919 5 1 theme neutral 695:701 arg1 oligosaccharides 703:718 neutral oligosaccharides 695:718 neutral oligosaccharides 695:718 They are all sialyl analogs of neutral oligosaccharides that were characterized previously [Lamblin G., Boersma A., Lhermitte M., Roussel P., Mutsaers J. H. G. M., Van Halbeek H. & Vliegenthart J. F. G. (1984) Eur. 3665919 8 2 dep either 943:948 arg1 -linkage 967:974 alpha (2----3)-linkage 953:974 alpha (2----3)-linkage to Gal 953:981 The NeuAc residue was found to occur either in alpha (2----3)-linkage to Gal, or in alpha (2----6)-linkage to GalNAc-ol or Gal. 3665919 4 3 from range 614:618 arg1 size 623:626 size 623:626 size 623:626 The established structures range in size from tetra- up to heptasaccharides. 3665919 5 4 theme oligosaccharides 703:718 arg1 analogs 684:690 all sialyl analogs 673:690 all sialyl analogs of neutral oligosaccharides that were characterized previously [Lamblin G., Boersma A., Lhermitte M., Roussel P., Mutsaers J. H. G. M., Van Halbeek H. & Vliegenthart J. F. G. (1984) Eur 673:876 They are all sialyl analogs of neutral oligosaccharides that were characterized previously [Lamblin G., Boersma A., Lhermitte M., Roussel P., Mutsaers J. H. G. M., Van Halbeek H. & Vliegenthart J. F. G. (1984) Eur. 3665919 5 4 theme oligosaccharides 703:718 arg1 They 664:667 They 664:667 They 664:667 They are all sialyl analogs of neutral oligosaccharides that were characterized previously [Lamblin G., Boersma A., Lhermitte M., Roussel P., Mutsaers J. H. G. M., Van Halbeek H. & Vliegenthart J. F. G. (1984) Eur. 3665919 8 5 dep occur 937:941 arg1 either 943:948 either 943:948 either 943:948 The NeuAc residue was found to occur either in alpha (2----3)-linkage to Gal, or in alpha (2----6)-linkage to GalNAc-ol or Gal. 3665919 8 5 dep occur 937:941 arg1 -linkage 1004:1011 alpha (2----6)-linkage 990:1011 alpha (2----6)-linkage to GalNAc-ol or Gal 990:1031 The NeuAc residue was found to occur either in alpha (2----3)-linkage to Gal, or in alpha (2----6)-linkage to GalNAc-ol or Gal. 3665919 0 6 theme group 100:104 arg1 O 106:106 blood group O 94:106 blood group O 94:106 Structure of sialyl-oligosaccharides isolated from bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis. 3665919 0 6 theme group 100:104 arg1 patients 84:91 patients 84:91 patients (blood group O) suffering from cystic fibrosis 84:138 Structure of sialyl-oligosaccharides isolated from bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis. 3665919 1 7 gly glycoproteins 188:200 arg1 glycoproteins 188:200 the bronchial-mucus glycoproteins 168:200 the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O 168:251 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 1 8 theme alkaline 270:277 arg1 treatment 291:299 alkaline borohydride treatment 270:299 alkaline borohydride treatment 270:299 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 5 9 dep F. 861:862 arg1 G 864:864 G 864:864 G., Boersma A., Lhermitte M., Roussel P., Mutsaers J. H. G. M., Van Halbeek H. & Vliegenthart J. F. G. (1984) Eur 764:876 They are all sialyl analogs of neutral oligosaccharides that were characterized previously [Lamblin G., Boersma A., Lhermitte M., Roussel P., Mutsaers J. H. G. M., Van Halbeek H. & Vliegenthart J. F. G. (1984) Eur. 3665919 3 10 theme sugar 571:575 arg1 analysis 577:584 quantitative sugar analysis 558:584 quantitative sugar analysis 558:584 Structural characterization was performed by 500-MHz 1H-NMR spectroscopy in combination with quantitative sugar analysis. 3665919 3 11 theme 500-MHz 510:516 arg1 spectroscopy 525:536 500-MHz 1H-NMR spectroscopy 510:536 500-MHz 1H-NMR spectroscopy 510:536 Structural characterization was performed by 500-MHz 1H-NMR spectroscopy in combination with quantitative sugar analysis. 3665919 4 12 theme established 591:601 arg1 structures 603:612 The established structures 587:612 The established structures 587:612 The established structures range in size from tetra- up to heptasaccharides. 3665919 8 13 theme alpha 990:994 arg1 -linkage 1004:1011 alpha (2----6)-linkage 990:1011 alpha (2----6)-linkage to GalNAc-ol or Gal 990:1031 The NeuAc residue was found to occur either in alpha (2----3)-linkage to Gal, or in alpha (2----6)-linkage to GalNAc-ol or Gal. 3665919 8 14 theme NeuAc 910:914 arg1 residue 916:922 The NeuAc residue 906:922 The NeuAc residue 906:922 The NeuAc residue was found to occur either in alpha (2----3)-linkage to Gal, or in alpha (2----6)-linkage to GalNAc-ol or Gal. 3665919 1 15 theme bronchial-mucus 172:186 arg1 glycoproteins 188:200 the bronchial-mucus glycoproteins 168:200 the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O 168:251 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 5 16 theme sialyl 677:682 arg1 analogs 684:690 all sialyl analogs 673:690 all sialyl analogs of neutral oligosaccharides that were characterized previously [Lamblin G., Boersma A., Lhermitte M., Roussel P., Mutsaers J. H. G. M., Van Halbeek H. & Vliegenthart J. F. G. (1984) Eur 673:876 They are all sialyl analogs of neutral oligosaccharides that were characterized previously [Lamblin G., Boersma A., Lhermitte M., Roussel P., Mutsaers J. H. G. M., Van Halbeek H. & Vliegenthart J. F. G. (1984) Eur. 3665919 5 16 theme sialyl 677:682 arg1 They 664:667 They 664:667 They 664:667 They are all sialyl analogs of neutral oligosaccharides that were characterized previously [Lamblin G., Boersma A., Lhermitte M., Roussel P., Mutsaers J. H. G. M., Van Halbeek H. & Vliegenthart J. F. G. (1984) Eur. 3665919 1 17 theme glycoproteins 188:200 arg1 chains 158:163 The carbohydrate chains 141:163 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O 141:251 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 3 18 theme Structural 465:474 arg1 characterization 476:491 Structural characterization 465:491 Structural characterization 465:491 Structural characterization was performed by 500-MHz 1H-NMR spectroscopy in combination with quantitative sugar analysis. 3665919 1 19 theme borohydride 279:289 arg1 treatment 291:299 alkaline borohydride treatment 270:299 alkaline borohydride treatment 270:299 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 8 20 theme 2----6 997:1002 arg1 -linkage 1004:1011 alpha (2----6)-linkage 990:1011 alpha (2----6)-linkage to GalNAc-ol or Gal 990:1031 The NeuAc residue was found to occur either in alpha (2----3)-linkage to Gal, or in alpha (2----6)-linkage to GalNAc-ol or Gal. 3665919 2 21 theme liquid 442:447 arg1 chromatography 449:462 high-performance liquid chromatography 425:462 high-performance liquid chromatography 425:462 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by high-performance liquid chromatography. 3665919 0 22 theme cystic 124:129 arg1 fibrosis 131:138 cystic fibrosis 124:138 cystic fibrosis 124:138 Structure of sialyl-oligosaccharides isolated from bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis. 3665919 2 23 theme monosialyl 322:331 arg1 oligosaccharide-alditols 333:356 monosialyl oligosaccharide-alditols 322:356 monosialyl oligosaccharide-alditols 322:356 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by high-performance liquid chromatography. 3665919 3 24 theme quantitative 558:569 arg1 analysis 577:584 quantitative sugar analysis 558:584 quantitative sugar analysis 558:584 Structural characterization was performed by 500-MHz 1H-NMR spectroscopy in combination with quantitative sugar analysis. 3665919 0 25 theme sialyl-oligosaccharides 13:35 arg1 Structure 0:8 Structure 0:8 Structure of sialyl-oligosaccharides 0:35 Structure of sialyl-oligosaccharides isolated from bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis. 3665919 1 26 with patients 225:232 arg1 O 251:251 blood group O 239:251 blood group O 239:251 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 1 27 theme cystic 209:214 arg1 fibrosis 216:223 cystic fibrosis 209:223 six cystic fibrosis patients with blood group O 205:251 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 0 28 theme bronchial 51:59 arg1 glycoproteins 67:79 bronchial mucus glycoproteins 51:79 bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis 51:138 Structure of sialyl-oligosaccharides isolated from bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis. 3665919 3 29 theme 1H-NMR 518:523 arg1 spectroscopy 525:536 500-MHz 1H-NMR spectroscopy 510:536 500-MHz 1H-NMR spectroscopy 510:536 Structural characterization was performed by 500-MHz 1H-NMR spectroscopy in combination with quantitative sugar analysis. 3665919 1 30 theme fibrosis 216:223 arg1 patients 225:232 six cystic fibrosis patients 205:232 six cystic fibrosis patients with blood group O 205:251 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 1 31 theme patients 225:232 arg1 glycoproteins 188:200 the bronchial-mucus glycoproteins 168:200 the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O 168:251 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 4 32 from tetra- 633:638 arg1 range 614:618 range 614:618 range 614:618 The established structures range in size from tetra- up to heptasaccharides. 3665919 0 33 theme mucus 61:65 arg1 glycoproteins 67:79 bronchial mucus glycoproteins 51:79 bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis 51:138 Structure of sialyl-oligosaccharides isolated from bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis. 3665919 3 34 with combination 541:551 arg1 analysis 577:584 quantitative sugar analysis 558:584 quantitative sugar analysis 558:584 Structural characterization was performed by 500-MHz 1H-NMR spectroscopy in combination with quantitative sugar analysis. 3665919 8 35 theme alpha 953:957 arg1 -linkage 967:974 alpha (2----3)-linkage 953:974 alpha (2----3)-linkage to Gal 953:981 The NeuAc residue was found to occur either in alpha (2----3)-linkage to Gal, or in alpha (2----6)-linkage to GalNAc-ol or Gal. 3665919 2 36 theme anion-exchange 375:388 arg1 chromatography 390:403 anion-exchange chromatography 375:403 anion-exchange chromatography 375:403 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by high-performance liquid chromatography. 3665919 8 37 theme 2----3 960:965 arg1 -linkage 967:974 alpha (2----3)-linkage 953:974 alpha (2----3)-linkage to Gal 953:981 The NeuAc residue was found to occur either in alpha (2----3)-linkage to Gal, or in alpha (2----6)-linkage to GalNAc-ol or Gal. 3665919 1 38 theme blood 239:243 arg1 O 251:251 blood group O 239:251 blood group O 239:251 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 0 39 theme patients 84:91 arg1 glycoproteins 67:79 bronchial mucus glycoproteins 51:79 bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis 51:138 Structure of sialyl-oligosaccharides isolated from bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis. 3665919 2 40 theme high-performance 425:440 arg1 chromatography 449:462 high-performance liquid chromatography 425:462 high-performance liquid chromatography 425:462 Low-molecular-mass, monosialyl oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by high-performance liquid chromatography. 3665919 1 41 theme group 245:249 arg1 O 251:251 blood group O 239:251 blood group O 239:251 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 3665919 0 42 gly glycoproteins 67:79 arg1 glycoproteins 67:79 bronchial mucus glycoproteins 51:79 bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis 51:138 Structure of sialyl-oligosaccharides isolated from bronchial mucus glycoproteins of patients (blood group O) suffering from cystic fibrosis. 3665919 1 43 theme carbohydrate 145:156 arg1 chains 158:163 The carbohydrate chains 141:163 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O 141:251 The carbohydrate chains of the bronchial-mucus glycoproteins of six cystic fibrosis patients with blood group O were released by alkaline borohydride treatment. 7540366 4 0 theme standard 661:668 arg1 oligosaccharides 677:692 The other 22 standard sialyl oligosaccharides 648:692 The other 22 standard sialyl oligosaccharides 648:692 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 9 1 theme map 1604:1606 arg1 layers 1586:1591 the layers 1582:1591 the layers of the 2-D map lined up on the Z-axis 1582:1629 By repeating the whole process for each group of different sialylation, the layers of the 2-D map lined up on the Z-axis form a 3-D map. 7540366 2 2 gly tetra-sialylated 492:507 arg1 oligosaccharides 391:406 42 different sialyl oligosaccharides 371:406 42 different sialyl oligosaccharides 371:406 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 2 gly tetra-sialylated 492:507 arg1 oligosaccharides 509:524 tetra-sialylated oligosaccharides 492:524 tetra-sialylated oligosaccharides 492:524 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 2 gly tetra-sialylated 492:507 arg1 2 477:477 2 477:477 2 477:477 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 2 gly tetra-sialylated 492:507 arg1 7 432:432 7 432:432 7 432:432 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 1 3 theme oligosaccharides 275:290 arg1 technique 150:158 a three-dimensional (3-D) sugar-mapping technique 110:158 a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides 110:219 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 1 3 theme oligosaccharides 275:290 arg1 characterization 246:261 a powerful structural characterization 224:261 a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples 224:322 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 6 4 theme amide-silica 1318:1329 arg1 columns 1340:1346 amide-silica (Y-axis) columns 1318:1346 amide-silica (Y-axis) columns 1318:1346 Then, neutral, mono-, di-, tri-, and tetra-sialyl oligosaccharides are individually separated on the octadecylsilyl (ODS)-silica (X-axis) and amide-silica (Y-axis) columns. 7540366 7 5 theme two-dimensional 1397:1411 arg1 map 1419:1421 a two-dimensional (2-D) map 1395:1421 a two-dimensional (2-D) map 1395:1421 The fourth step is to plot the coordinates on a two-dimensional (2-D) map. 7540366 9 6 theme whole 1527:1531 arg1 process 1533:1539 the whole process 1523:1539 the whole process for each group of different sialylation 1523:1579 By repeating the whole process for each group of different sialylation, the layers of the 2-D map lined up on the Z-axis form a 3-D map. 7540366 4 7 theme sialyl 670:675 arg1 oligosaccharides 677:692 The other 22 standard sialyl oligosaccharides 648:692 The other 22 standard sialyl oligosaccharides 648:692 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 3 8 attach released 572:579 arg2 oligosaccharides 550:565 The 20 standard sialyl oligosaccharides 527:565 The 20 standard sialyl oligosaccharides 527:565 The 20 standard sialyl oligosaccharides were released from human serum and calf fetuin by digestion with glycoamidase A. 7540366 3 8 attach released 572:579 arg1 serum 592:596 human serum 586:596 human serum 586:596 The 20 standard sialyl oligosaccharides were released from human serum and calf fetuin by digestion with glycoamidase A. 7540366 3 8 attach released 572:579 arg1 fetuin 607:612 calf fetuin 602:612 calf fetuin 602:612 The 20 standard sialyl oligosaccharides were released from human serum and calf fetuin by digestion with glycoamidase A. 7540366 2 9 from oligosaccharides 391:406 arg1 data 361:364 the elution data 349:364 the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides 349:524 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 4 10 theme sialyl 748:753 arg1 oligosaccharides 755:770 the above 20 sialyl oligosaccharides 735:770 the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase 735:877 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 2 11 theme new 329:331 arg1 map 333:335 The new map 325:335 The new map 325:335 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 1 12 theme only 298:301 arg1 picomoles 303:311 only picomoles 298:311 only picomoles of samples 298:322 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 5 13 theme PA-oligosaccharide 974:991 arg1 mixture 993:999 a neutral and sialyl PA-oligosaccharide mixture 953:999 a neutral and sialyl PA-oligosaccharide mixture 953:999 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 6 14 theme tetra-sialyl 1213:1224 arg1 oligosaccharides 1226:1241 tetra-sialyl oligosaccharides 1213:1241 tetra-sialyl oligosaccharides 1213:1241 Then, neutral, mono-, di-, tri-, and tetra-sialyl oligosaccharides are individually separated on the octadecylsilyl (ODS)-silica (X-axis) and amide-silica (Y-axis) columns. 7540366 6 14 theme tetra-sialyl 1213:1224 arg1 neutral 1182:1188 neutral 1182:1188 neutral 1182:1188 Then, neutral, mono-, di-, tri-, and tetra-sialyl oligosaccharides are individually separated on the octadecylsilyl (ODS)-silica (X-axis) and amide-silica (Y-axis) columns. 7540366 2 15 theme different 374:382 arg1 oligosaccharides 391:406 42 different sialyl oligosaccharides 371:406 42 different sialyl oligosaccharides 371:406 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 4 16 theme specific 860:867 arg1 sialidase 869:877 alpha 2-->3 specific sialidase 848:877 alpha 2-->3 specific sialidase 848:877 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 5 17 theme 3-D 892:894 arg1 method 904:909 The present 3-D mapping method 880:909 The present 3-D mapping method 880:909 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 2 18 theme 2 477:477 arg1 di- 447:449 di- 447:449 di- 447:449 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 5 19 theme following 924:932 arg1 steps 939:943 the following four steps 920:943 the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis) 920:1173 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 4 20 theme 2-->3 854:858 arg1 sialidase 869:877 alpha 2-->3 specific sialidase 848:877 alpha 2-->3 specific sialidase 848:877 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 4 21 theme oligosaccharides 755:770 arg1 digestion 722:730 subsequent digestion 711:730 subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase 711:877 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 5 22 theme present 884:890 arg1 method 904:909 The present 3-D mapping method 880:909 The present 3-D mapping method 880:909 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 0 23 theme elution 18:24 arg1 mapping 26:32 Three-dimensional elution mapping 0:32 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides 0:96 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides. 7540366 5 24 theme elution 1107:1113 arg1 one 1138:1140 one 1138:1140 one 1138:1140 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 5 24 theme elution 1107:1113 arg1 dimensions 1155:1164 the three dimensions 1145:1164 the three dimensions (Z-axis) 1145:1173 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 5 24 theme elution 1107:1113 arg1 data 1115:1118 the elution data 1103:1118 the elution data 1103:1118 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 1 25 link N-linked 266:273 arg1 oligosaccharides 275:290 N-linked oligosaccharides 266:290 N-linked oligosaccharides using only picomoles of samples 266:322 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 3 26 theme sialyl 543:548 arg1 oligosaccharides 550:565 The 20 standard sialyl oligosaccharides 527:565 The 20 standard sialyl oligosaccharides 527:565 The 20 standard sialyl oligosaccharides were released from human serum and calf fetuin by digestion with glycoamidase A. 7540366 4 27 theme other 652:656 arg1 oligosaccharides 677:692 The other 22 standard sialyl oligosaccharides 648:692 The other 22 standard sialyl oligosaccharides 648:692 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 0 28 theme Three-dimensional 0:16 arg1 mapping 26:32 Three-dimensional elution mapping 0:32 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides 0:96 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides. 7540366 3 29 theme standard 534:541 arg1 oligosaccharides 550:565 The 20 standard sialyl oligosaccharides 527:565 The 20 standard sialyl oligosaccharides 527:565 The 20 standard sialyl oligosaccharides were released from human serum and calf fetuin by digestion with glycoamidase A. 7540366 9 30 theme different 1559:1567 arg1 sialylation 1569:1579 different sialylation 1559:1579 different sialylation 1559:1579 By repeating the whole process for each group of different sialylation, the layers of the 2-D map lined up on the Z-axis form a 3-D map. 7540366 0 31 link N-linked 53:60 arg1 oligosaccharides 81:96 pyridylaminated N-linked neutral and sialyl oligosaccharides 37:96 pyridylaminated N-linked neutral and sialyl oligosaccharides 37:96 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides. 7540366 7 32 theme fourth 1353:1358 arg1 step 1360:1363 The fourth step 1349:1363 The fourth step 1349:1363 The fourth step is to plot the coordinates on a two-dimensional (2-D) map. 7540366 1 33 theme sialyl 197:202 arg1 oligosaccharides 204:219 sialyl oligosaccharides 197:219 sialyl oligosaccharides 197:219 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 1 34 theme samples 316:322 arg1 picomoles 303:311 only picomoles 298:311 only picomoles of samples 298:322 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 9 35 theme sialylation 1569:1579 arg1 process 1533:1539 the whole process 1523:1539 the whole process for each group of different sialylation 1523:1579 By repeating the whole process for each group of different sialylation, the layers of the 2-D map lined up on the Z-axis form a 3-D map. 7540366 1 36 theme three-dimensional 112:128 arg1 technique 150:158 a three-dimensional (3-D) sugar-mapping technique 110:158 a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides 110:219 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 1 36 theme three-dimensional 112:128 arg1 characterization 246:261 a powerful structural characterization 224:261 a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples 224:322 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 3 37 with digestion 617:625 arg1 A 645:645 glycoamidase A 632:645 glycoamidase A 632:645 The 20 standard sialyl oligosaccharides were released from human serum and calf fetuin by digestion with glycoamidase A. 7540366 2 38 theme 7 432:432 arg1 di- 447:449 di- 447:449 di- 447:449 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 5 39 theme neutral 955:961 arg1 mixture 993:999 a neutral and sialyl PA-oligosaccharide mixture 953:999 a neutral and sialyl PA-oligosaccharide mixture 953:999 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 1 40 dep pyridylaminated 164:178 arg1 PA 181:182 PA 181:182 PA 181:182 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 2 41 theme oligosaccharides 391:406 arg1 di- 447:449 di- 447:449 di- 447:449 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 41 theme oligosaccharides 391:406 arg1 oligosaccharides 391:406 42 different sialyl oligosaccharides 371:406 42 different sialyl oligosaccharides 371:406 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 41 theme oligosaccharides 391:406 arg1 oligosaccharides 509:524 tetra-sialylated oligosaccharides 492:524 tetra-sialylated oligosaccharides 492:524 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 41 theme oligosaccharides 391:406 arg1 7 432:432 7 432:432 7 432:432 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 41 theme oligosaccharides 391:406 arg1 26 409:410 26 409:410 26 409:410 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 41 theme oligosaccharides 391:406 arg1 2 477:477 2 477:477 2 477:477 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 0 42 theme N-linked 53:60 arg1 oligosaccharides 81:96 pyridylaminated N-linked neutral and sialyl oligosaccharides 37:96 pyridylaminated N-linked neutral and sialyl oligosaccharides 37:96 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides. 7540366 7 43 dep two-dimensional 1397:1411 arg1 2-D 1414:1416 2-D 1414:1416 2-D 1414:1416 The fourth step is to plot the coordinates on a two-dimensional (2-D) map. 7540366 6 44 theme ODS 1293:1295 arg1 X-axis 1306:1311 X-axis 1306:1311 X-axis 1306:1311 Then, neutral, mono-, di-, tri-, and tetra-sialyl oligosaccharides are individually separated on the octadecylsilyl (ODS)-silica (X-axis) and amide-silica (Y-axis) columns. 7540366 6 44 theme ODS 1293:1295 arg1 -silica 1297:1303 the octadecylsilyl (ODS)-silica 1273:1303 the octadecylsilyl (ODS)-silica (X-axis) 1273:1312 Then, neutral, mono-, di-, tri-, and tetra-sialyl oligosaccharides are individually separated on the octadecylsilyl (ODS)-silica (X-axis) and amide-silica (Y-axis) columns. 7540366 3 45 theme glycoamidase 632:643 arg1 A 645:645 glycoamidase A 632:645 glycoamidase A 632:645 The 20 standard sialyl oligosaccharides were released from human serum and calf fetuin by digestion with glycoamidase A. 7540366 5 46 theme mapping 896:902 arg1 method 904:909 The present 3-D mapping method 880:909 The present 3-D mapping method 880:909 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 0 47 theme pyridylaminated 37:51 arg1 oligosaccharides 81:96 pyridylaminated N-linked neutral and sialyl oligosaccharides 37:96 pyridylaminated N-linked neutral and sialyl oligosaccharides 37:96 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides. 7540366 6 48 theme Y-axis 1332:1337 arg1 columns 1340:1346 amide-silica (Y-axis) columns 1318:1346 amide-silica (Y-axis) columns 1318:1346 Then, neutral, mono-, di-, tri-, and tetra-sialyl oligosaccharides are individually separated on the octadecylsilyl (ODS)-silica (X-axis) and amide-silica (Y-axis) columns. 7540366 2 49 theme tetra-sialylated 492:507 arg1 oligosaccharides 391:406 42 different sialyl oligosaccharides 371:406 42 different sialyl oligosaccharides 371:406 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 49 theme tetra-sialylated 492:507 arg1 oligosaccharides 509:524 tetra-sialylated oligosaccharides 492:524 tetra-sialylated oligosaccharides 492:524 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 49 theme tetra-sialylated 492:507 arg1 2 477:477 2 477:477 2 477:477 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 49 theme tetra-sialylated 492:507 arg1 7 432:432 7 432:432 7 432:432 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 5 50 theme acid 1085:1088 arg1 content 1090:1096 the sialic acid content 1074:1096 the sialic acid content 1074:1096 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 3 51 theme human 586:590 arg1 serum 592:596 human serum 586:596 human serum 586:596 The 20 standard sialyl oligosaccharides were released from human serum and calf fetuin by digestion with glycoamidase A. 7540366 1 52 theme powerful 226:233 arg1 technique 150:158 a three-dimensional (3-D) sugar-mapping technique 110:158 a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides 110:219 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 1 52 theme powerful 226:233 arg1 characterization 246:261 a powerful structural characterization 224:261 a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples 224:322 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 2 53 theme 7 452:452 arg1 di- 447:449 di- 447:449 di- 447:449 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 2 53 theme 7 452:452 arg1 tri- 467:470 tri- 467:470 tri- 467:470 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 8 54 theme DEAE 1470:1473 arg1 column 1475:1480 the DEAE column 1466:1480 the DEAE column 1466:1480 Thus, for each of the groups separated on the DEAE column, a 2-D map can be achieved. 7540366 6 55 theme octadecylsilyl 1277:1290 arg1 X-axis 1306:1311 X-axis 1306:1311 X-axis 1306:1311 Then, neutral, mono-, di-, tri-, and tetra-sialyl oligosaccharides are individually separated on the octadecylsilyl (ODS)-silica (X-axis) and amide-silica (Y-axis) columns. 7540366 6 55 theme octadecylsilyl 1277:1290 arg1 -silica 1297:1303 the octadecylsilyl (ODS)-silica 1273:1303 the octadecylsilyl (ODS)-silica (X-axis) 1273:1312 Then, neutral, mono-, di-, tri-, and tetra-sialyl oligosaccharides are individually separated on the octadecylsilyl (ODS)-silica (X-axis) and amide-silica (Y-axis) columns. 7540366 4 56 with oligosaccharides 755:770 arg1 beta-N-acetylhexosaminidase 797:823 beta-N-acetylhexosaminidase 797:823 beta-N-acetylhexosaminidase 797:823 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 4 56 with oligosaccharides 755:770 arg1 sialidase 869:877 alpha 2-->3 specific sialidase 848:877 alpha 2-->3 specific sialidase 848:877 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 4 56 with oligosaccharides 755:770 arg1 beta-galactosidase 777:794 beta-galactosidase 777:794 beta-galactosidase 777:794 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 4 56 with oligosaccharides 755:770 arg1 alpha-fucosidase 826:841 alpha-fucosidase 826:841 alpha-fucosidase 826:841 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 4 57 theme alpha 848:852 arg1 sialidase 869:877 alpha 2-->3 specific sialidase 848:877 alpha 2-->3 specific sialidase 848:877 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 0 58 theme neutral 62:68 arg1 oligosaccharides 81:96 pyridylaminated N-linked neutral and sialyl oligosaccharides 37:96 pyridylaminated N-linked neutral and sialyl oligosaccharides 37:96 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides. 7540366 5 59 theme DEAE 1048:1051 arg1 column 1054:1059 the diethylaminoethyl (DEAE) column 1025:1059 the diethylaminoethyl (DEAE) column according to the sialic acid content 1025:1096 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 9 60 theme 3-D 1638:1640 arg1 map 1642:1644 a 3-D map 1636:1644 a 3-D map 1636:1644 By repeating the whole process for each group of different sialylation, the layers of the 2-D map lined up on the Z-axis form a 3-D map. 7540366 4 61 theme subsequent 711:720 arg1 digestion 722:730 subsequent digestion 711:730 subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase 711:877 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 9 62 theme 2-D 1600:1602 arg1 map 1604:1606 the 2-D map 1596:1606 the 2-D map lined up on the Z-axis 1596:1629 By repeating the whole process for each group of different sialylation, the layers of the 2-D map lined up on the Z-axis form a 3-D map. 7540366 3 63 theme calf 602:605 arg1 fetuin 607:612 calf fetuin 602:612 calf fetuin 602:612 The 20 standard sialyl oligosaccharides were released from human serum and calf fetuin by digestion with glycoamidase A. 7540366 5 64 theme diethylaminoethyl 1029:1045 arg1 column 1054:1059 the diethylaminoethyl (DEAE) column 1025:1059 the diethylaminoethyl (DEAE) column according to the sialic acid content 1025:1096 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 1 65 theme sugar-mapping 136:148 arg1 technique 150:158 a three-dimensional (3-D) sugar-mapping technique 110:158 a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides 110:219 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 1 65 theme sugar-mapping 136:148 arg1 characterization 246:261 a powerful structural characterization 224:261 a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples 224:322 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 4 66 theme above 739:743 arg1 oligosaccharides 755:770 the above 20 sialyl oligosaccharides 735:770 the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase 735:877 The other 22 standard sialyl oligosaccharides were obtained by subsequent digestion of the above 20 sialyl oligosaccharides with beta-galactosidase, beta-N-acetylhexosaminidase, alpha-fucosidase, and alpha 2-->3 specific sialidase. 7540366 1 67 theme structural 235:244 arg1 technique 150:158 a three-dimensional (3-D) sugar-mapping technique 110:158 a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides 110:219 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 1 67 theme structural 235:244 arg1 characterization 246:261 a powerful structural characterization 224:261 a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples 224:322 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 5 68 dep steps 939:943 arg1 separated 1004:1012 separated 1004:1012 is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content 1001:1096 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 5 68 dep steps 939:943 arg1 considered 1124:1133 considered 1124:1133 are considered as one of the three dimensions (Z-axis) 1120:1173 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 5 69 theme sialyl 967:972 arg1 mixture 993:999 a neutral and sialyl PA-oligosaccharide mixture 953:999 a neutral and sialyl PA-oligosaccharide mixture 953:999 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 5 70 theme sialic 1078:1083 arg1 content 1090:1096 the sialic acid content 1074:1096 the sialic acid content 1074:1096 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 2 71 theme elution 353:359 arg1 data 361:364 the elution data 349:364 the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides 349:524 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 0 72 theme oligosaccharides 81:96 arg1 mapping 26:32 Three-dimensional elution mapping 0:32 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides 0:96 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides. 7540366 7 73 from plot 1371:1374 arg1 map 1419:1421 a two-dimensional (2-D) map 1395:1421 a two-dimensional (2-D) map 1395:1421 The fourth step is to plot the coordinates on a two-dimensional (2-D) map. 7540366 1 74 dep three-dimensional 112:128 arg1 3-D 131:133 3-D 131:133 3-D 131:133 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7540366 5 75 theme dimensions 1155:1164 arg1 one 1138:1140 one 1138:1140 one 1138:1140 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 5 75 theme dimensions 1155:1164 arg1 Z-axis 1167:1172 Z-axis 1167:1172 Z-axis 1167:1172 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 5 75 theme dimensions 1155:1164 arg1 data 1115:1118 the elution data 1103:1118 the elution data 1103:1118 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 5 75 theme dimensions 1155:1164 arg1 dimensions 1155:1164 the three dimensions 1145:1164 the three dimensions (Z-axis) 1145:1173 The present 3-D mapping method involves the following four steps: First, a neutral and sialyl PA-oligosaccharide mixture is separated by HPLC on the diethylaminoethyl (DEAE) column according to the sialic acid content, and the elution data are considered as one of the three dimensions (Z-axis). 7540366 0 76 theme sialyl 74:79 arg1 oligosaccharides 81:96 pyridylaminated N-linked neutral and sialyl oligosaccharides 37:96 pyridylaminated N-linked neutral and sialyl oligosaccharides 37:96 Three-dimensional elution mapping of pyridylaminated N-linked neutral and sialyl oligosaccharides. 7540366 8 77 theme 2-D 1485:1487 arg1 map 1489:1491 a 2-D map 1483:1491 a 2-D map 1483:1491 Thus, for each of the groups separated on the DEAE column, a 2-D map can be achieved. 7540366 2 78 theme sialyl 384:389 arg1 oligosaccharides 391:406 42 different sialyl oligosaccharides 371:406 42 different sialyl oligosaccharides 371:406 The new map consists of the elution data from 42 different sialyl oligosaccharides, 26 of which are mono-, 7 of which are di-, 7 of which are tri-, and 2 of which are tetra-sialylated oligosaccharides. 7540366 1 79 theme N-linked 266:273 arg1 oligosaccharides 275:290 N-linked oligosaccharides 266:290 N-linked oligosaccharides using only picomoles of samples 266:322 We propose a three-dimensional (3-D) sugar-mapping technique for pyridylaminated (PA) neutral and sialyl oligosaccharides as a powerful structural characterization of N-linked oligosaccharides using only picomoles of samples. 7060557 4 0 theme GlcNAc 1164:1169 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 1 theme cleavage 543:550 arg1 beta 849:852 beta 1-2 849:856 beta 1-2 849:856 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 1 theme cleavage 543:550 arg1 GlcNAc 842:847 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc 461:847 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 461:995 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 5 2 theme other 1188:1192 arg1 glycopeptides 1194:1206 Two other glycopeptides 1184:1206 Two other glycopeptides 1184:1206 Two other glycopeptides were obtained in very low amount and possess more complex structures. 7060557 4 3 theme [Fuc 1148:1151 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 4 theme [NeuAc 670:675 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 5 theme beta 877:880 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 6 theme Glycopeptide 796:807 arg1 C 809:809 Glycopeptide C 796:809 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal 579:831 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 7 theme Man 918:920 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 8 theme alpha 1153:1157 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 1 9 attach linked 165:170 arg1 sites 138:142 two glycoslyation sites 120:142 two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous 120:270 The polypeptide chain of human lactotransferrin possesses two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous. 7060557 1 9 attach linked 165:170 arg2 glycans 153:159 glycans 153:159 glycans 153:159 The polypeptide chain of human lactotransferrin possesses two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous. 7060557 4 10 theme [Gal 1073:1076 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 11 theme alpha 677:681 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 12 theme alpha 922:926 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 13 theme beta 1171:1174 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 1 14 contain possesses 110:118 arg1 chain 78:82 The polypeptide chain 62:82 The polypeptide chain of human lactotransferrin 62:108 The polypeptide chain of human lactotransferrin possesses two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous. 7060557 1 14 contain possesses 110:118 arg2 sites 138:142 two glycoslyation sites 120:142 two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous 120:270 The polypeptide chain of human lactotransferrin possesses two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous. 7060557 3 15 theme beta 937:940 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 1 16 theme glycoslyation 124:136 arg1 sites 138:142 two glycoslyation sites 120:142 two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous 120:270 The polypeptide chain of human lactotransferrin possesses two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous. 7060557 3 17 theme Man 933:935 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 18 theme beta 707:710 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 19 theme Gal 627:629 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 20 dep MHz 583:585 arg1 C 809:809 Glycopeptide C 796:809 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal 579:831 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 20 dep MHz 583:585 arg1 Glycopeptides 588:600 Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 588:793 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal 579:831 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 20 dep MHz 583:585 arg1 Gal 829:831 Gal 829:831 Gal 829:831 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 20 dep MHz 583:585 arg1 alpha 818:822 alpha 2-6 818:826 alpha 2-6 818:826 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 20 dep MHz 583:585 arg1 NeuAc 812:816 NeuAc 812:816 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal 579:831 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 21 theme Glycopeptide 998:1009 arg1 D 1011:1011 Glycopeptide D 998:1011 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 22 dep Glycopeptides 588:600 arg1 Asn 791:793 A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 602:793 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal 579:831 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 2 23 with glycopeptides 315:327 arg1 structures 356:365 five different glycan structures 334:365 five different glycan structures 334:365 After chymotryptic or pronase digestions, glycopeptides with five different glycan structures could be isolated. 7060557 4 24 theme beta 1078:1081 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 25 from MHz 583:585 arg1 cleavage 543:550 enzymatic cleavage 533:550 enzymatic cleavage 533:550 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 25 from MHz 583:585 arg1 methanolysis 461:472 methanolysis 461:472 methanolysis 461:472 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 25 from MHz 583:585 arg1 deamination 520:530 hydrazinolysis/nitrous deamination 497:530 hydrazinolysis/nitrous deamination 497:530 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 25 from MHz 583:585 arg1 spectroscopy 563:574 1H-NMR spectroscopy 556:574 1H-NMR spectroscopy 556:574 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 25 from MHz 583:585 arg1 beta 833:836 beta 1-4 833:840 beta 1-4 833:840 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 25 from MHz 583:585 arg1 analysis 487:494 methylation analysis 475:494 methylation analysis 475:494 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 26 theme GlcNAc 842:847 arg1 alpha 862:866 alpha 1-3 862:870 alpha 1-3 862:870 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 26 theme GlcNAc 842:847 arg1 Man 858:860 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man 461:860 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 461:995 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 2 27 theme glycan 349:354 arg1 structures 356:365 five different glycan structures 334:365 five different glycan structures 334:365 After chymotryptic or pronase digestions, glycopeptides with five different glycan structures could be isolated. 7060557 3 28 theme GlcNAc 744:749 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 29 theme Gal 1030:1032 arg1 alpha 1063:1067 alpha 1-3 1063:1071 alpha 1-3 1063:1071 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 29 theme Gal 1030:1032 arg1 Man 1059:1061 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man 1014:1061 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 0 30 theme Primary 0:6 arg1 structure 8:16 Primary structure 0:16 Primary structure of the glycans from human lactotransferrin 0:59 Primary structure of the glycans from human lactotransferrin. 7060557 1 31 theme human 87:91 arg1 lactotransferrin 93:108 human lactotransferrin 87:108 human lactotransferrin 87:108 The polypeptide chain of human lactotransferrin possesses two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous. 7060557 4 32 theme GlcNAc 1087:1092 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 33 theme beta 1139:1142 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 34 theme methylation 475:485 arg1 analysis 487:494 methylation analysis 475:494 methylation analysis 475:494 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 2 35 theme pronase 295:301 arg1 digestions 303:312 chymotryptic or pronase digestions 279:312 chymotryptic or pronase digestions 279:312 After chymotryptic or pronase digestions, glycopeptides with five different glycan structures could be isolated. 7060557 3 36 theme beta 985:988 arg1 Asn 993:995 GlcNAc(beta 1-)Asn 978:995 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 461:995 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 37 theme methanolysis 461:472 arg1 beta 849:852 beta 1-2 849:856 beta 1-2 849:856 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 37 theme methanolysis 461:472 arg1 GlcNAc 842:847 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc 461:847 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 461:995 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 0 38 theme glycans 25:31 arg1 structure 8:16 Primary structure 0:16 Primary structure of the glycans from human lactotransferrin 0:59 Primary structure of the glycans from human lactotransferrin. 7060557 3 39 theme GlcNAc 700:705 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 40 theme GlcNAc 776:781 arg1 Asn 791:793 A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 602:793 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal 579:831 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 41 theme beta 631:634 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 42 theme GlcNAc 978:983 arg1 Asn 993:995 GlcNAc(beta 1-)Asn 978:995 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 461:995 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 43 theme deamination 520:530 arg1 beta 849:852 beta 1-2 849:856 beta 1-2 849:856 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 43 theme deamination 520:530 arg1 GlcNAc 842:847 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc 461:847 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 461:995 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 0 44 theme human 38:42 arg1 lactotransferrin 44:59 human lactotransferrin 38:59 human lactotransferrin 38:59 Primary structure of the glycans from human lactotransferrin. 7060557 4 45 theme Glc-NAc 1131:1137 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 46 theme beta 1034:1037 arg1 alpha 1063:1067 alpha 1-3 1063:1071 alpha 1-3 1063:1071 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 46 theme beta 1034:1037 arg1 Man 1059:1061 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man 1014:1061 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 2 47 gly glycopeptides 315:327 arg2 glycopeptides 315:327 glycopeptides 315:327 glycopeptides with five different glycan structures 315:365 After chymotryptic or pronase digestions, glycopeptides with five different glycan structures could be isolated. 7060557 3 48 theme alpha 660:664 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 49 theme enzymatic 533:541 arg1 cleavage 543:550 enzymatic cleavage 533:550 enzymatic cleavage 533:550 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 50 theme Man 656:658 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 51 theme [Fuc 886:889 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 5 52 theme complex 1258:1264 arg1 structures 1266:1275 more complex structures 1253:1275 more complex structures 1253:1275 Two other glycopeptides were obtained in very low amount and possess more complex structures. 7060557 3 53 theme spectroscopy 563:574 arg1 beta 849:852 beta 1-2 849:856 beta 1-2 849:856 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 53 theme spectroscopy 563:574 arg1 GlcNAc 842:847 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc 461:847 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 461:995 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 54 dep B 608:608 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 5 55 contain possess 1245:1251 arg2 structures 1266:1275 more complex structures 1253:1275 more complex structures 1253:1275 Two other glycopeptides were obtained in very low amount and possess more complex structures. 7060557 5 55 contain possess 1245:1251 arg1 glycopeptides 1194:1206 Two other glycopeptides 1184:1206 Two other glycopeptides 1184:1206 Two other glycopeptides were obtained in very low amount and possess more complex structures. 7060557 2 56 theme different 339:347 arg1 structures 356:365 five different glycan structures 334:365 five different glycan structures 334:365 After chymotryptic or pronase digestions, glycopeptides with five different glycan structures could be isolated. 7060557 5 57 gly glycopeptides 1194:1206 arg2 glycopeptides 1194:1206 Two other glycopeptides 1184:1206 Two other glycopeptides 1184:1206 Two other glycopeptides were obtained in very low amount and possess more complex structures. 7060557 3 58 theme Gal 687:689 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 59 theme alpha 891:895 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 60 theme NeuAc 611:615 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 1 61 theme -N-acetylglucosaminylamine 200:225 arg1 heterogenous 259:270 heterogenous 259:270 heterogenous 259:270 The polypeptide chain of human lactotransferrin possesses two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous. 7060557 1 61 theme -N-acetylglucosaminylamine 200:225 arg1 bond 227:230 an N-(beta-aspartyl)-N-acetylglucosaminylamine bond 180:230 an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous 180:270 The polypeptide chain of human lactotransferrin possesses two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous. 7060557 3 62 theme beta 909:912 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 63 theme B 608:608 arg1 GlcNAc 776:781 and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc 604:781 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal 579:831 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 63 theme B 608:608 arg1 beta 783:786 beta 1- 783:789 beta 1- 783:789 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 64 theme GlcNAc 902:907 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 65 dep D 1011:1011 arg1 alpha 1063:1067 alpha 1-3 1063:1071 alpha 1-3 1063:1071 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 65 dep D 1011:1011 arg1 Man 1059:1061 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man 1014:1061 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 66 theme beta 691:694 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 2 67 theme chymotryptic 279:290 arg1 digestions 303:312 chymotryptic or pronase digestions 279:312 chymotryptic or pronase digestions 279:312 After chymotryptic or pronase digestions, glycopeptides with five different glycan structures could be isolated. 7060557 3 68 theme Man 731:733 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 69 dep Man 1059:1061 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 70 theme alpha 617:621 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 71 theme hydrazinolysis/nitrous 497:518 arg1 deamination 520:530 hydrazinolysis/nitrous deamination 497:530 hydrazinolysis/nitrous deamination 497:530 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 72 theme beta 953:956 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 0 73 from structure 8:16 arg1 lactotransferrin 44:59 human lactotransferrin 38:59 human lactotransferrin 38:59 Primary structure of the glycans from human lactotransferrin. 7060557 3 74 theme GlcNAc 946:951 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 75 theme alpha 720:724 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 76 dep Man 858:860 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 76 dep Man 858:860 arg1 Asn 993:995 GlcNAc(beta 1-)Asn 978:995 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 461:995 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 77 theme beta 735:738 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 0 78 from lactotransferrin 44:59 arg1 structure 8:16 Primary structure 0:16 Primary structure of the glycans from human lactotransferrin 0:59 Primary structure of the glycans from human lactotransferrin. 7060557 0 78 from lactotransferrin 44:59 arg1 glycans 25:31 the glycans 21:31 the glycans from human lactotransferrin 21:59 Primary structure of the glycans from human lactotransferrin. 7060557 4 79 theme Man 1118:1120 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 80 theme Man 716:718 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 1 81 theme polypeptide 66:76 arg1 chain 78:82 The polypeptide chain 62:82 The polypeptide chain of human lactotransferrin 62:108 The polypeptide chain of human lactotransferrin possesses two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous. 7060557 4 82 theme Man 1103:1105 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 83 theme alpha 1020:1024 arg1 alpha 1063:1067 alpha 1-3 1063:1071 alpha 1-3 1063:1071 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 83 theme alpha 1020:1024 arg1 Man 1059:1061 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man 1014:1061 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 84 theme alpha 1107:1111 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 1 85 theme lactotransferrin 93:108 arg1 chain 78:82 The polypeptide chain 62:82 The polypeptide chain of human lactotransferrin 62:108 The polypeptide chain of human lactotransferrin possesses two glycoslyation sites to which glycans are linked through an N-(beta-aspartyl)-N-acetylglucosaminylamine bond and which are structurally heterogenous. 7060557 4 86 theme beta 1094:1097 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 87 theme them 399:402 arg1 them 399:402 them 399:402 them 399:402 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 87 theme them 399:402 arg1 three 390:394 three 390:394 three 390:394 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 5 88 theme low 1230:1232 arg1 amount 1234:1239 very low amount 1225:1239 very low amount 1225:1239 Two other glycopeptides were obtained in very low amount and possess more complex structures. 7060557 3 89 theme analysis 487:494 arg1 beta 849:852 beta 1-2 849:856 beta 1-2 849:856 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 89 theme analysis 487:494 arg1 GlcNAc 842:847 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc 461:847 methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 461:995 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 90 theme NeuAc 1014:1018 arg1 alpha 1063:1067 alpha 1-3 1063:1071 alpha 1-3 1063:1071 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 90 theme NeuAc 1014:1018 arg1 Man 1059:1061 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man 1014:1061 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 91 theme beta 1122:1125 arg1 Asn 1179:1181 [Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 1073:1181 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 92 theme beta 647:650 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 93 theme GlcNAc 1043:1048 arg1 alpha 1063:1067 alpha 1-3 1063:1071 alpha 1-3 1063:1071 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 93 theme GlcNAc 1043:1048 arg1 Man 1059:1061 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man 1014:1061 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 94 theme Man 858:860 arg1 application 446:456 the application 442:456 the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn 442:995 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 95 dep [Fuc 962:965 arg1 alpha 967:971 alpha 1-6 967:975 alpha 1-6 967:975 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 96 theme GlcNAc 640:645 arg1 [Fuc 760:763 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc 611:763 B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6) 608:774 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 97 theme beta 1050:1053 arg1 alpha 1063:1067 alpha 1-3 1063:1071 alpha 1-3 1063:1071 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 4 97 theme beta 1050:1053 arg1 Man 1059:1061 NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man 1014:1061 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 998:1182 Glycopeptide D: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)Glc-NAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 98 theme Gal 873:875 arg1 [Fuc 962:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc 873:965 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 7060557 3 99 theme 1H-NMR 556:561 arg1 spectroscopy 563:574 1H-NMR spectroscopy 556:574 1H-NMR spectroscopy 556:574 For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 1H-NMR spectroscopy at 360 MHz: Glycopeptides A and B: NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)[NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta-1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn; Glycopeptide C: NeuAc(alpha 2-6)(Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1-3)(Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-2)Man(alpha 1-6))Man(beta 1-4)GlcNAc(beta 1-4)[Fuc(alpha 1-6)]GlcNAc(beta 1-)Asn. 6684483 2 0 gly glycopeptides 432:444 arg2 glycopeptides 432:444 its glycopeptides 428:444 its glycopeptides prepared using pronase digestion 428:477 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 1 1 theme N-linked 155:162 arg1 chains 180:185 two biantennary N-linked oligosaccharide chains 139:185 two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type 139:217 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 0 2 theme globulin 68:75 arg1 moiety 26:31 the carbohydrate moiety 9:31 the carbohydrate moiety of human serum sex hormone-binding globulin 9:75 Study of the carbohydrate moiety of human serum sex hormone-binding globulin. 6684483 1 3 link O-linked 227:234 arg1 oligosaccharide 236:250 one O-linked oligosaccharide 223:250 one O-linked oligosaccharide per one molecule of the glycoprotein 223:287 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 1 4 theme oligosaccharide 164:178 arg1 chains 180:185 two biantennary N-linked oligosaccharide chains 139:185 two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type 139:217 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 1 5 theme glycoprotein 276:287 arg1 molecule 260:267 one molecule 256:267 one molecule of the glycoprotein 256:287 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 2 6 theme whole 370:374 arg1 glycoprotein 376:387 whole glycoprotein 370:387 whole glycoprotein 370:387 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 2 7 theme structures 414:423 arg1 investigation 393:405 investigation 393:405 investigation 393:405 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 2 7 theme structures 414:423 arg1 glycoprotein 376:387 whole glycoprotein 370:387 whole glycoprotein 370:387 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 1 8 from serum 124:128 arg1 globulin 98:105 Sex hormone-binding globulin 78:105 Sex hormone-binding globulin from human blood serum 78:128 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 2 9 dep glycoprotein 376:387 arg1 the 366:368 the 366:368 the 366:368 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 1 10 theme Sex 78:80 arg1 globulin 98:105 Sex hormone-binding globulin 78:105 Sex hormone-binding globulin from human blood serum 78:128 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 1 11 theme hormone-binding 82:96 arg1 globulin 98:105 Sex hormone-binding globulin 78:105 Sex hormone-binding globulin from human blood serum 78:128 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 1 12 theme N-acetyllactosamine 194:212 arg1 type 214:217 the N-acetyllactosamine type 190:217 the N-acetyllactosamine type 190:217 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 0 13 theme carbohydrate 13:24 arg1 moiety 26:31 the carbohydrate moiety 9:31 the carbohydrate moiety of human serum sex hormone-binding globulin 9:75 Study of the carbohydrate moiety of human serum sex hormone-binding globulin. 6684483 1 14 link N-linked 155:162 arg1 chains 180:185 two biantennary N-linked oligosaccharide chains 139:185 two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type 139:217 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 1 15 gly glycoprotein 276:287 arg1 glycoprotein 276:287 the glycoprotein 272:287 the glycoprotein 272:287 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 1 16 theme type 214:217 arg1 chains 180:185 two biantennary N-linked oligosaccharide chains 139:185 two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type 139:217 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 1 16 theme type 214:217 arg1 oligosaccharide 236:250 one O-linked oligosaccharide 223:250 one O-linked oligosaccharide per one molecule of the glycoprotein 223:287 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 2 17 theme glycopeptides 432:444 arg1 structures 414:423 the structures 410:423 the structures of its glycopeptides prepared using pronase digestion 410:477 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 2 18 theme analysis 354:361 arg1 results 331:337 the results 327:337 the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion 327:477 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 2 19 theme investigation 393:405 arg1 analysis 354:361 methylation analysis 342:361 methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion 342:477 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 0 20 theme moiety 26:31 arg1 Study 0:4 Study 0:4 Study of the carbohydrate moiety of human serum sex hormone-binding globulin. 0:76 Study of the carbohydrate moiety of human serum sex hormone-binding globulin. 6684483 2 21 theme pronase 461:467 arg1 digestion 469:477 pronase digestion 461:477 pronase digestion 461:477 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 1 22 theme O-linked 227:234 arg1 oligosaccharide 236:250 one O-linked oligosaccharide 223:250 one O-linked oligosaccharide per one molecule of the glycoprotein 223:287 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 0 23 theme serum 42:46 arg1 globulin 68:75 human serum sex hormone-binding globulin 36:75 human serum sex hormone-binding globulin 36:75 Study of the carbohydrate moiety of human serum sex hormone-binding globulin. 6684483 1 24 theme human 112:116 arg1 serum 124:128 human blood serum 112:128 human blood serum 112:128 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 0 25 theme human 36:40 arg1 globulin 68:75 human serum sex hormone-binding globulin 36:75 human serum sex hormone-binding globulin 36:75 Study of the carbohydrate moiety of human serum sex hormone-binding globulin. 6684483 2 26 gly glycoprotein 376:387 arg1 glycoprotein 376:387 whole glycoprotein 370:387 whole glycoprotein 370:387 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 1 27 theme blood 118:122 arg1 serum 124:128 human blood serum 112:128 human blood serum 112:128 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 2 28 theme methylation 342:352 arg1 analysis 354:361 methylation analysis 342:361 methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion 342:477 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 2 29 theme glycoprotein 376:387 arg1 analysis 354:361 methylation analysis 342:361 methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion 342:477 These conclusions have been based on the results of methylation analysis of the whole glycoprotein and investigation of the structures of its glycopeptides prepared using pronase digestion. 6684483 0 30 theme hormone-binding 52:66 arg1 globulin 68:75 human serum sex hormone-binding globulin 36:75 human serum sex hormone-binding globulin 36:75 Study of the carbohydrate moiety of human serum sex hormone-binding globulin. 6684483 0 31 theme sex 48:50 arg1 globulin 68:75 human serum sex hormone-binding globulin 36:75 human serum sex hormone-binding globulin 36:75 Study of the carbohydrate moiety of human serum sex hormone-binding globulin. 6684483 1 32 contain contains 130:137 arg2 oligosaccharide 236:250 one O-linked oligosaccharide 223:250 one O-linked oligosaccharide per one molecule of the glycoprotein 223:287 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 1 32 contain contains 130:137 arg1 globulin 98:105 Sex hormone-binding globulin 78:105 Sex hormone-binding globulin from human blood serum 78:128 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 1 32 contain contains 130:137 arg2 chains 180:185 two biantennary N-linked oligosaccharide chains 139:185 two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type 139:217 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 6684483 1 33 theme biantennary 143:153 arg1 chains 180:185 two biantennary N-linked oligosaccharide chains 139:185 two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type 139:217 Sex hormone-binding globulin from human blood serum contains two biantennary N-linked oligosaccharide chains of the N-acetyllactosamine type and one O-linked oligosaccharide per one molecule of the glycoprotein. 7541354 5 0 theme sugar 629:633 arg1 mapping 635:641 two-dimensional sugar mapping 613:641 two-dimensional sugar mapping 613:641 The asialo forms were then analyzed by two-dimensional sugar mapping, component sugar analysis and 400-MHz 1H-NMR spectroscopy. 7541354 6 1 theme human 732:736 arg1 vitronectin 738:748 human vitronectin 732:748 human vitronectin 732:748 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 1 2 link N-linked 91:98 arg1 oligosaccharides 100:115 N-linked oligosaccharides 91:115 N-linked oligosaccharides present on human plasma vitronectin 91:151 The structures of N-linked oligosaccharides present on human plasma vitronectin were elucidated. 7541354 6 3 theme 2-3 981:983 arg1 linkages 985:992 alpha 2-3 linkages 975:992 alpha 2-3 linkages 975:992 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 7 4 theme human 1195:1199 arg1 vitronectin 1201:1211 human vitronectin 1195:1211 human vitronectin revealed here 1195:1225 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 0 5 link N-linked 18:25 arg1 oligosaccharides 27:42 the N-linked oligosaccharides 14:42 the N-linked oligosaccharides 14:42 Structures of the N-linked oligosaccharides on human plasma vitronectin. 7541354 0 6 from Structures 0:9 arg1 vitronectin 60:70 human plasma vitronectin 47:70 human plasma vitronectin 47:70 Structures of the N-linked oligosaccharides on human plasma vitronectin. 7541354 7 7 theme binding 1042:1048 arg1 activities 1050:1059 several binding activities 1034:1059 several binding activities of vitronectin 1034:1074 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 4 8 theme sialic 468:473 arg1 residues 480:487 sialic acid residues 468:487 sialic acid residues 468:487 The linkages and locations of sialic acid residues were determined by desialylation with Salmonella sialidase in combination with acid. 7541354 1 9 theme present 117:123 arg1 oligosaccharides 100:115 N-linked oligosaccharides 91:115 N-linked oligosaccharides present on human plasma vitronectin 91:151 The structures of N-linked oligosaccharides present on human plasma vitronectin were elucidated. 7541354 7 10 theme oligosaccharides 1175:1190 arg1 features 1150:1157 the specific features 1137:1157 the specific features of the N-linked oligosaccharides on human vitronectin revealed here 1137:1225 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 5 11 theme asialo 578:583 arg1 forms 585:589 The asialo forms 574:589 The asialo forms 574:589 The asialo forms were then analyzed by two-dimensional sugar mapping, component sugar analysis and 400-MHz 1H-NMR spectroscopy. 7541354 4 12 theme residues 480:487 arg1 locations 455:463 locations 455:463 locations 455:463 The linkages and locations of sialic acid residues were determined by desialylation with Salmonella sialidase in combination with acid. 7541354 4 12 theme residues 480:487 arg1 linkages 442:449 linkages 442:449 linkages 442:449 The linkages and locations of sialic acid residues were determined by desialylation with Salmonella sialidase in combination with acid. 7541354 4 13 with combination 551:561 arg1 acid 568:571 acid 568:571 acid 568:571 The linkages and locations of sialic acid residues were determined by desialylation with Salmonella sialidase in combination with acid. 7541354 6 14 theme lesser 807:812 arg1 amount 814:819 a lesser amount 805:819 a lesser amount of the tri- 805:831 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 14 theme lesser 807:812 arg1 tri- 828:831 the tri- 824:831 the tri- 824:831 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 14 theme lesser 807:812 arg1 type 874:877 the mono-antennary type 855:877 the mono-antennary type 855:877 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 15 theme major 706:710 arg1 oligosaccharides 712:727 The major oligosaccharides 702:727 The major oligosaccharides of human vitronectin 702:748 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 7 16 theme specific 1141:1148 arg1 features 1150:1157 the specific features 1137:1157 the specific features of the N-linked oligosaccharides on human vitronectin revealed here 1137:1225 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 6 17 theme mol 893:895 arg1 residues 909:916 1-3 mol sialic acid residues 889:916 1-3 mol sialic acid residues 889:916 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 5 18 theme 400-MHz 673:679 arg1 spectroscopy 688:699 400-MHz 1H-NMR spectroscopy 673:699 400-MHz 1H-NMR spectroscopy 673:699 The asialo forms were then analyzed by two-dimensional sugar mapping, component sugar analysis and 400-MHz 1H-NMR spectroscopy. 7541354 1 19 theme N-linked 91:98 arg1 oligosaccharides 100:115 N-linked oligosaccharides 91:115 N-linked oligosaccharides present on human plasma vitronectin 91:151 The structures of N-linked oligosaccharides present on human plasma vitronectin were elucidated. 7541354 0 20 theme N-linked 18:25 arg1 oligosaccharides 27:42 the N-linked oligosaccharides 14:42 the N-linked oligosaccharides 14:42 Structures of the N-linked oligosaccharides on human plasma vitronectin. 7541354 6 21 theme type 874:877 arg1 amount 845:850 a small amount 837:850 a small amount 837:850 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 21 theme type 874:877 arg1 amount 814:819 a lesser amount 805:819 a lesser amount of the tri- 805:831 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 21 theme type 874:877 arg1 tri- 828:831 the tri- 824:831 the tri- 824:831 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 21 theme type 874:877 arg1 type 874:877 the mono-antennary type 855:877 the mono-antennary type 855:877 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 5 22 theme 1H-NMR 681:686 arg1 spectroscopy 688:699 400-MHz 1H-NMR spectroscopy 673:699 400-MHz 1H-NMR spectroscopy 673:699 The asialo forms were then analyzed by two-dimensional sugar mapping, component sugar analysis and 400-MHz 1H-NMR spectroscopy. 7541354 1 23 theme oligosaccharides 100:115 arg1 structures 77:86 The structures 73:86 The structures of N-linked oligosaccharides present on human plasma vitronectin 73:151 The structures of N-linked oligosaccharides present on human plasma vitronectin were elucidated. 7541354 4 24 theme acid 475:478 arg1 residues 480:487 sialic acid residues 468:487 sialic acid residues 468:487 The linkages and locations of sialic acid residues were determined by desialylation with Salmonella sialidase in combination with acid. 7541354 7 25 link N-linked 1166:1173 arg1 oligosaccharides 1175:1190 the N-linked oligosaccharides 1162:1190 the N-linked oligosaccharides on human vitronectin revealed here 1162:1225 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 2 26 theme reverse-phase 363:375 arg1 HPLC 377:380 anion-exchange and reverse-phase HPLC 344:380 HPLC 377:380 Oligosaccharides were released from the vitronectin by N-glycosidase F digestion and tagged with 2-aminopyridine; the pyridylamino-oligosaccharides were then fractionated by anion-exchange and reverse-phase HPLC. 7541354 6 27 theme alpha 946:950 arg1 linkages 956:963 alpha 2-6 linkages 946:963 alpha 2-6 linkages 946:963 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 2 28 theme anion-exchange 344:357 arg1 HPLC 377:380 anion-exchange and reverse-phase HPLC 344:380 HPLC 377:380 Oligosaccharides were released from the vitronectin by N-glycosidase F digestion and tagged with 2-aminopyridine; the pyridylamino-oligosaccharides were then fractionated by anion-exchange and reverse-phase HPLC. 7541354 6 29 attach linked 923:928 arg1 amount 845:850 a small amount 837:850 a small amount 837:850 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 29 attach linked 923:928 arg1 tri- 828:831 the tri- 824:831 the tri- 824:831 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 29 attach linked 923:928 arg2 residues 909:916 1-3 mol sialic acid residues 889:916 1-3 mol sialic acid residues 889:916 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 29 attach linked 923:928 arg1 type 874:877 the mono-antennary type 855:877 the mono-antennary type 855:877 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 4 30 from sialidase 538:546 arg1 combination 551:561 combination 551:561 combination with acid 551:571 The linkages and locations of sialic acid residues were determined by desialylation with Salmonella sialidase in combination with acid. 7541354 4 31 theme Salmonella 527:536 arg1 sialidase 538:546 Salmonella sialidase 527:546 Salmonella sialidase in combination with acid 527:571 The linkages and locations of sialic acid residues were determined by desialylation with Salmonella sialidase in combination with acid. 7541354 6 32 theme N-acetyllactosamine 774:792 arg1 type 794:797 the diantennary N-acetyllactosamine type 758:797 the diantennary N-acetyllactosamine type 758:797 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 0 33 theme oligosaccharides 27:42 arg1 Structures 0:9 Structures 0:9 Structures of the N-linked oligosaccharides on human plasma vitronectin 0:70 Structures of the N-linked oligosaccharides on human plasma vitronectin. 7541354 2 34 attach released 192:199 arg2 Oligosaccharides 170:185 Oligosaccharides 170:185 Oligosaccharides 170:185 Oligosaccharides were released from the vitronectin by N-glycosidase F digestion and tagged with 2-aminopyridine; the pyridylamino-oligosaccharides were then fractionated by anion-exchange and reverse-phase HPLC. 7541354 2 34 attach released 192:199 arg1 vitronectin 210:220 the vitronectin 206:220 the vitronectin 206:220 Oligosaccharides were released from the vitronectin by N-glycosidase F digestion and tagged with 2-aminopyridine; the pyridylamino-oligosaccharides were then fractionated by anion-exchange and reverse-phase HPLC. 7541354 0 35 theme plasma 53:58 arg1 vitronectin 60:70 human plasma vitronectin 47:70 human plasma vitronectin 47:70 Structures of the N-linked oligosaccharides on human plasma vitronectin. 7541354 7 36 from oligosaccharides 1175:1190 arg1 vitronectin 1201:1211 human vitronectin 1195:1211 human vitronectin revealed here 1195:1225 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 6 37 with type 794:797 arg1 amount 845:850 a small amount 837:850 a small amount 837:850 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 37 with type 794:797 arg1 amount 814:819 a lesser amount 805:819 a lesser amount of the tri- 805:831 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 37 with type 794:797 arg1 tri- 828:831 the tri- 824:831 the tri- 824:831 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 37 with type 794:797 arg1 type 874:877 the mono-antennary type 855:877 the mono-antennary type 855:877 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 7 38 from features 1150:1157 arg1 vitronectin 1201:1211 human vitronectin 1195:1211 human vitronectin revealed here 1195:1225 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 0 39 theme human 47:51 arg1 vitronectin 60:70 human plasma vitronectin 47:70 human plasma vitronectin 47:70 Structures of the N-linked oligosaccharides on human plasma vitronectin. 7541354 1 40 attach present 117:123 arg2 oligosaccharides 100:115 N-linked oligosaccharides 91:115 N-linked oligosaccharides present on human plasma vitronectin 91:151 The structures of N-linked oligosaccharides present on human plasma vitronectin were elucidated. 7541354 1 40 attach present 117:123 arg1 vitronectin 141:151 human plasma vitronectin 128:151 human plasma vitronectin 128:151 The structures of N-linked oligosaccharides present on human plasma vitronectin were elucidated. 7541354 2 41 theme F 239:239 arg1 digestion 241:249 N-glycosidase F digestion 225:249 N-glycosidase F digestion 225:249 Oligosaccharides were released from the vitronectin by N-glycosidase F digestion and tagged with 2-aminopyridine; the pyridylamino-oligosaccharides were then fractionated by anion-exchange and reverse-phase HPLC. 7541354 5 42 theme component 644:652 arg1 analysis 660:667 component sugar analysis 644:667 component sugar analysis 644:667 The asialo forms were then analyzed by two-dimensional sugar mapping, component sugar analysis and 400-MHz 1H-NMR spectroscopy. 7541354 1 43 theme human 128:132 arg1 vitronectin 141:151 human plasma vitronectin 128:151 human plasma vitronectin 128:151 The structures of N-linked oligosaccharides present on human plasma vitronectin were elucidated. 7541354 6 44 theme diantennary 762:772 arg1 type 794:797 the diantennary N-acetyllactosamine type 758:797 the diantennary N-acetyllactosamine type 758:797 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 45 theme mono-antennary 859:872 arg1 type 874:877 the mono-antennary type 855:877 the mono-antennary type 855:877 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 7 46 theme glycan 1099:1104 arg1 moiety 1106:1111 its glycan moiety 1095:1111 its glycan moiety 1095:1111 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 2 47 theme N-glycosidase 225:237 arg1 digestion 241:249 N-glycosidase F digestion 225:249 N-glycosidase F digestion 225:249 Oligosaccharides were released from the vitronectin by N-glycosidase F digestion and tagged with 2-aminopyridine; the pyridylamino-oligosaccharides were then fractionated by anion-exchange and reverse-phase HPLC. 7541354 6 48 theme sialic 897:902 arg1 residues 909:916 1-3 mol sialic acid residues 889:916 1-3 mol sialic acid residues 889:916 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 5 49 theme sugar 654:658 arg1 analysis 660:667 component sugar analysis 644:667 component sugar analysis 644:667 The asialo forms were then analyzed by two-dimensional sugar mapping, component sugar analysis and 400-MHz 1H-NMR spectroscopy. 7541354 1 50 theme plasma 134:139 arg1 vitronectin 141:151 human plasma vitronectin 128:151 human plasma vitronectin 128:151 The structures of N-linked oligosaccharides present on human plasma vitronectin were elucidated. 7541354 6 51 theme tri- 828:831 arg1 amount 845:850 a small amount 837:850 a small amount 837:850 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 51 theme tri- 828:831 arg1 amount 814:819 a lesser amount 805:819 a lesser amount of the tri- 805:831 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 51 theme tri- 828:831 arg1 tri- 828:831 the tri- 824:831 the tri- 824:831 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 51 theme tri- 828:831 arg1 type 874:877 the mono-antennary type 855:877 the mono-antennary type 855:877 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 52 theme small 839:843 arg1 amount 845:850 a small amount 837:850 a small amount 837:850 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 52 theme small 839:843 arg1 tri- 828:831 the tri- 824:831 the tri- 824:831 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 6 52 theme small 839:843 arg1 type 874:877 the mono-antennary type 855:877 the mono-antennary type 855:877 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 7 53 theme vitronectin 1064:1074 arg1 activities 1050:1059 several binding activities 1034:1059 several binding activities of vitronectin 1034:1074 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 7 54 theme N-linked 1166:1173 arg1 oligosaccharides 1175:1190 the N-linked oligosaccharides 1162:1190 the N-linked oligosaccharides on human vitronectin revealed here 1162:1225 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 3 55 theme major 387:391 arg1 pyridylamino-oligosaccharides 393:421 Ten major pyridylamino-oligosaccharides 383:421 Ten major pyridylamino-oligosaccharides 383:421 Ten major pyridylamino-oligosaccharides were isolated. 7541354 6 56 theme acid 904:907 arg1 residues 909:916 1-3 mol sialic acid residues 889:916 1-3 mol sialic acid residues 889:916 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 7 57 theme several 1034:1040 arg1 activities 1050:1059 several binding activities 1034:1059 several binding activities of vitronectin 1034:1074 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 4 58 dep linkages 442:449 arg1 The 438:440 The 438:440 The 438:440 The linkages and locations of sialic acid residues were determined by desialylation with Salmonella sialidase in combination with acid. 7541354 6 59 theme alpha 975:979 arg1 linkages 985:992 alpha 2-3 linkages 975:992 alpha 2-3 linkages 975:992 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7541354 7 60 from vitronectin 1201:1211 arg1 features 1150:1157 the specific features 1137:1157 the specific features of the N-linked oligosaccharides on human vitronectin revealed here 1137:1225 The possibility that several binding activities of vitronectin can be ascribed to its glycan moiety was discussed, based on the specific features of the N-linked oligosaccharides on human vitronectin revealed here. 7541354 5 61 theme two-dimensional 613:627 arg1 mapping 635:641 two-dimensional sugar mapping 613:641 two-dimensional sugar mapping 613:641 The asialo forms were then analyzed by two-dimensional sugar mapping, component sugar analysis and 400-MHz 1H-NMR spectroscopy. 7541354 6 62 theme vitronectin 738:748 arg1 oligosaccharides 712:727 The major oligosaccharides 702:727 The major oligosaccharides of human vitronectin 702:748 The major oligosaccharides of human vitronectin were of the diantennary N-acetyllactosamine type, with a lesser amount of the tri- and a small amount of the mono-antennary type, to which 1-3 mol sialic acid residues were linked, mostly through alpha 2-6 linkages, although alpha 2-3 linkages were also present. 7514386 4 0 theme CD59 519:522 arg1 U-CD59 534:539 U-CD59 534:539 U-CD59 534:539 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 4 0 theme CD59 519:522 arg1 form 511:514 a soluble form 501:514 a soluble form of CD59 in urine 501:531 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 12 1 theme detailed 1684:1691 arg1 analysis 1693:1700 the first detailed analysis 1674:1700 the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein 1674:1776 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 10 2 theme sugar 1330:1334 arg1 chains 1336:1341 the asparagine-linked sugar chains 1308:1341 the asparagine-linked sugar chains of U-CD59 1308:1351 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 7 3 contain containing 912:921 arg1 peptide 904:910 the peptide 900:910 the peptide containing a glycan portion of the GPI anchor 900:956 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 7 3 contain containing 912:921 arg2 portion 932:938 a glycan portion 923:938 a glycan portion of the GPI anchor 923:956 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 10 4 theme complex 1370:1376 arg1 structures 1294:1303 The structures 1290:1303 The structures of the asparagine-linked sugar chains of U-CD59 1290:1351 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 10 4 theme complex 1370:1376 arg1 type 1378:1381 biantennary complex type 1358:1381 biantennary complex type 1358:1381 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 10 4 theme complex 1370:1376 arg1 % 1392:1392 only 4.2% 1384:1392 only 4.2% of which are monosialylated 1384:1420 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 8 5 theme anchor 1076:1081 arg1 portion 1057:1063 the glycan portion 1046:1063 the glycan portion of the GPI anchor 1046:1081 The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. 7514386 8 5 theme anchor 1076:1081 arg1 chains 1035:1040 The asparagine-linked sugar chains 1007:1040 The asparagine-linked sugar chains 1007:1040 The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. 7514386 12 6 theme anchor 1663:1668 arg1 analysis 1693:1700 the first detailed analysis 1674:1700 the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein 1674:1776 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 12 6 theme anchor 1663:1668 arg1 analysis 1637:1644 the first detailed structural analysis 1607:1644 the first detailed structural analysis of the human GPI anchor 1607:1668 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 12 6 theme anchor 1663:1668 arg1 This 1599:1602 This 1599:1602 This 1599:1602 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 10 7 link asparagine-linked 1312:1328 arg1 chains 1336:1341 the asparagine-linked sugar chains 1308:1341 the asparagine-linked sugar chains of U-CD59 1308:1351 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 7 8 link asparagine-linked 866:882 arg1 chain 890:894 an asparagine-linked sugar chain 863:894 an asparagine-linked sugar chain 863:894 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 7 9 theme trypsin 978:984 arg1 digestion 986:994 trypsin digestion 978:994 trypsin digestion of U-CD59 978:1004 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 8 10 link asparagine-linked 1011:1027 arg1 chains 1035:1040 The asparagine-linked sugar chains 1007:1040 The asparagine-linked sugar chains 1007:1040 The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. 7514386 11 11 from variations 1560:1569 arg1 moieties 1589:1596 its side-chain moieties 1574:1596 its side-chain moieties 1574:1596 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 0 12 theme CD59 120:123 arg1 form 112:115 a soluble form 102:115 a soluble form of CD59 102:123 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 1 13 theme human 192:196 arg1 cells 198:202 human cells 192:202 human cells 192:202 CD59 is an 18-kDa glycoprotein widely expressed on human cells. 7514386 0 14 from chain 93:97 arg1 urine 134:138 human urine 128:138 human urine 128:138 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 0 15 theme human 128:132 arg1 urine 134:138 human urine 128:138 human urine 128:138 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 2 16 theme structural 218:227 arg1 attachment 252:261 its attachment 248:261 its attachment to the cell surface 248:281 An important structural feature of CD59 is its attachment to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor. 7514386 2 16 theme structural 218:227 arg1 feature 229:235 An important structural feature 205:235 An important structural feature of CD59 205:243 An important structural feature of CD59 is its attachment to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor. 7514386 6 17 theme U-CD59 832:837 arg1 terminus 820:827 the carboxy terminus 808:827 the carboxy terminus of U-CD59 808:837 This indicates that a GPI anchor, which ended with inositol, is linked at the carboxy terminus of U-CD59. 7514386 7 18 contain containing 852:861 arg1 peptide 844:850 The peptide 840:850 The peptide containing an asparagine-linked sugar chain 840:894 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 7 18 contain containing 852:861 arg2 chain 890:894 an asparagine-linked sugar chain 863:894 an asparagine-linked sugar chain 863:894 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 11 19 theme backbone 1427:1434 arg1 similar 1468:1474 similar 1468:1474 similar 1468:1474 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 11 19 theme backbone 1427:1434 arg1 structure 1436:1444 The backbone structure 1423:1444 The backbone structure of the GPI anchor 1423:1462 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 12 20 theme GPI 1659:1661 arg1 anchor 1663:1668 the human GPI anchor 1649:1668 the human GPI anchor 1649:1668 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 0 21 theme asparagine-linked 69:85 arg1 chain 93:97 the asparagine-linked sugar chain 65:97 the asparagine-linked sugar chain 65:97 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 13 22 theme glycan-phosphatidylinositol-specific 1993:2028 arg1 D 2044:2044 glycan-phosphatidylinositol-specific phospholipase D 1993:2044 glycan-phosphatidylinositol-specific phospholipase D 1993:2044 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 7 23 theme asparagine-linked 866:882 arg1 chain 890:894 an asparagine-linked sugar chain 863:894 an asparagine-linked sugar chain 863:894 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 12 24 theme detailed 1617:1624 arg1 This 1599:1602 This 1599:1602 This 1599:1602 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 12 24 theme detailed 1617:1624 arg1 analysis 1637:1644 the first detailed structural analysis 1607:1644 the first detailed structural analysis of the human GPI anchor 1607:1668 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 11 25 theme GPI 1453:1455 arg1 anchor 1457:1462 the GPI anchor 1449:1462 the GPI anchor 1449:1462 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 5 26 theme inositol 689:696 arg1 present 698:704 inositol present 689:704 inositol present 689:704 Purified U-CD59 released 1 mol of inositol per mole of protein by nitrous acid deamination, which cleaved between glucosamine and inositol present commonly in the GPI anchor. 7514386 13 27 theme D 2044:2044 arg1 action 1983:1988 the action 1979:1988 the action of glycan-phosphatidylinositol-specific phospholipase D 1979:2044 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 4 28 theme anchor 453:458 arg1 structures 431:440 The structures 427:440 The structures of the GPI anchor 427:458 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 4 28 theme anchor 453:458 arg1 chain 492:496 the asparagine-linked sugar chain 464:496 the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, 464:540 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 11 29 theme anchor 1457:1462 arg1 similar 1468:1474 similar 1468:1474 similar 1468:1474 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 11 29 theme anchor 1457:1462 arg1 structure 1436:1444 The backbone structure 1423:1444 The backbone structure of the GPI anchor 1423:1462 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 13 30 theme backbone 1809:1816 arg1 structure 1818:1826 the backbone structure 1805:1826 the backbone structure of the GPI anchor 1805:1844 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 0 31 theme form 112:115 arg1 chain 93:97 the asparagine-linked sugar chain 65:97 the asparagine-linked sugar chain 65:97 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 0 31 theme form 112:115 arg1 anchor 54:59 the glycosyl-phosphatidylinositol anchor 20:59 the glycosyl-phosphatidylinositol anchor 20:59 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 9 32 theme exoglycosidase 1239:1252 arg1 digestion 1254:1262 sequential exoglycosidase digestion 1228:1262 sequential exoglycosidase digestion 1228:1262 Their structures were analyzed by sequential exoglycosidase digestion and methylation analyses. 7514386 0 33 theme Structural 0:9 arg1 study 11:15 Structural study 0:15 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 0:139 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 3 34 theme many 344:347 arg1 proteins 362:369 many GPI-anchored proteins 344:369 many GPI-anchored proteins 344:369 CD59, like many GPI-anchored proteins, has been found in urine, serum, and other body fluids. 7514386 3 35 theme body 414:417 arg1 fluids 419:424 other body fluids 408:424 other body fluids 408:424 CD59, like many GPI-anchored proteins, has been found in urine, serum, and other body fluids. 7514386 4 36 theme soluble 503:509 arg1 U-CD59 534:539 U-CD59 534:539 U-CD59 534:539 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 4 36 theme soluble 503:509 arg1 form 511:514 a soluble form 501:514 a soluble form of CD59 in urine 501:531 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 6 37 attach linked 798:803 arg3 terminus 820:827 the carboxy terminus 808:827 the carboxy terminus of U-CD59 808:837 This indicates that a GPI anchor, which ended with inositol, is linked at the carboxy terminus of U-CD59. 7514386 6 37 attach linked 798:803 arg2 anchor 760:765 a GPI anchor 754:765 a GPI anchor 754:765 This indicates that a GPI anchor, which ended with inositol, is linked at the carboxy terminus of U-CD59. 7514386 11 38 gly glycoprotein 1523:1534 arg1 glycoprotein 1523:1534 Try-panosoma brucei variant surface glycoprotein 1487:1534 Try-panosoma brucei variant surface glycoprotein 1487:1534 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 0 39 theme glycosyl-phosphatidylinositol 24:52 arg1 anchor 54:59 the glycosyl-phosphatidylinositol anchor 20:59 the glycosyl-phosphatidylinositol anchor 20:59 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 12 40 theme GPI-anchored 1757:1768 arg1 protein 1770:1776 the soluble-form GPI-anchored protein 1740:1776 the soluble-form GPI-anchored protein 1740:1776 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 6 41 theme GPI 756:758 arg1 anchor 760:765 a GPI anchor 754:765 a GPI anchor 754:765 This indicates that a GPI anchor, which ended with inositol, is linked at the carboxy terminus of U-CD59. 7514386 4 42 theme sugar 486:490 arg1 chain 492:496 the asparagine-linked sugar chain 464:496 the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, 464:540 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 11 43 theme Try-panosoma 1487:1498 arg1 glycoprotein 1523:1534 Try-panosoma brucei variant surface glycoprotein 1487:1534 Try-panosoma brucei variant surface glycoprotein 1487:1534 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 11 44 theme surface 1515:1521 arg1 glycoprotein 1523:1534 Try-panosoma brucei variant surface glycoprotein 1487:1534 Try-panosoma brucei variant surface glycoprotein 1487:1534 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 2 45 theme GPI 320:322 arg1 anchor 325:330 a glycosyl-phosphatidylinositol (GPI) anchor 287:330 a glycosyl-phosphatidylinositol (GPI) anchor 287:330 An important structural feature of CD59 is its attachment to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor. 7514386 12 46 theme structure 1727:1735 arg1 analysis 1693:1700 the first detailed analysis 1674:1700 the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein 1674:1776 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 12 46 theme structure 1727:1735 arg1 analysis 1637:1644 the first detailed structural analysis 1607:1644 the first detailed structural analysis of the human GPI anchor 1607:1668 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 12 46 theme structure 1727:1735 arg1 This 1599:1602 This 1599:1602 This 1599:1602 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 13 47 theme soluble-form 1915:1926 arg1 protein 1941:1947 the soluble-form GPI-anchored protein 1911:1947 the soluble-form GPI-anchored protein 1911:1947 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 8 48 theme sugar 1029:1033 arg1 chains 1035:1040 The asparagine-linked sugar chains 1007:1040 The asparagine-linked sugar chains 1007:1040 The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. 7514386 6 49 theme carboxy 812:818 arg1 terminus 820:827 the carboxy terminus 808:827 the carboxy terminus of U-CD59 808:837 This indicates that a GPI anchor, which ended with inositol, is linked at the carboxy terminus of U-CD59. 7514386 13 50 contain has 1949:1951 arg2 structure 1957:1965 the structure 1953:1965 the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D 1953:2044 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 13 50 contain has 1949:1951 arg1 part 1903:1906 a part 1901:1906 at least a part of the soluble-form GPI-anchored protein 1892:1947 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 1 51 gly glycoprotein 159:170 arg1 CD59 141:144 CD59 141:144 CD59 141:144 CD59 is an 18-kDa glycoprotein widely expressed on human cells. 7514386 1 51 gly glycoprotein 159:170 arg1 glycoprotein 159:170 an 18-kDa glycoprotein 149:170 an 18-kDa glycoprotein widely expressed on human cells 149:202 CD59 is an 18-kDa glycoprotein widely expressed on human cells. 7514386 13 52 theme protein 1941:1947 arg1 part 1903:1906 a part 1901:1906 at least a part of the soluble-form GPI-anchored protein 1892:1947 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 11 53 theme brucei 1500:1505 arg1 glycoprotein 1523:1534 Try-panosoma brucei variant surface glycoprotein 1487:1534 Try-panosoma brucei variant surface glycoprotein 1487:1534 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 7 54 theme U-CD59 999:1004 arg1 digestion 986:994 trypsin digestion 978:994 trypsin digestion of U-CD59 978:1004 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 10 55 theme chains 1336:1341 arg1 structures 1294:1303 The structures 1290:1303 The structures of the asparagine-linked sugar chains of U-CD59 1290:1351 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 10 55 theme chains 1336:1341 arg1 type 1378:1381 biantennary complex type 1358:1381 biantennary complex type 1358:1381 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 2 56 theme cell 270:273 arg1 surface 275:281 the cell surface 266:281 the cell surface 266:281 An important structural feature of CD59 is its attachment to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor. 7514386 8 57 theme glycan 1050:1055 arg1 portion 1057:1063 the glycan portion 1046:1063 the glycan portion of the GPI anchor 1046:1081 The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. 7514386 10 58 theme asparagine-linked 1312:1328 arg1 chains 1336:1341 the asparagine-linked sugar chains 1308:1341 the asparagine-linked sugar chains of U-CD59 1308:1351 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 1 59 theme 18-kDa 152:157 arg1 CD59 141:144 CD59 141:144 CD59 141:144 CD59 is an 18-kDa glycoprotein widely expressed on human cells. 7514386 1 59 theme 18-kDa 152:157 arg1 glycoprotein 159:170 an 18-kDa glycoprotein 149:170 an 18-kDa glycoprotein widely expressed on human cells 149:202 CD59 is an 18-kDa glycoprotein widely expressed on human cells. 7514386 4 60 link asparagine-linked 468:484 arg1 chain 492:496 the asparagine-linked sugar chain 464:496 the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, 464:540 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 5 61 theme Purified 559:566 arg1 U-CD59 568:573 Purified U-CD59 559:573 Purified U-CD59 559:573 Purified U-CD59 released 1 mol of inositol per mole of protein by nitrous acid deamination, which cleaved between glucosamine and inositol present commonly in the GPI anchor. 7514386 10 62 theme biantennary 1358:1368 arg1 structures 1294:1303 The structures 1290:1303 The structures of the asparagine-linked sugar chains of U-CD59 1290:1351 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 10 62 theme biantennary 1358:1368 arg1 type 1378:1381 biantennary complex type 1358:1381 biantennary complex type 1358:1381 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 10 62 theme biantennary 1358:1368 arg1 % 1392:1392 only 4.2% 1384:1392 only 4.2% of which are monosialylated 1384:1420 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 2 63 theme glycosyl-phosphatidylinositol 289:317 arg1 anchor 325:330 a glycosyl-phosphatidylinositol (GPI) anchor 287:330 a glycosyl-phosphatidylinositol (GPI) anchor 287:330 An important structural feature of CD59 is its attachment to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor. 7514386 8 64 theme GPI 1072:1074 arg1 anchor 1076:1081 the GPI anchor 1068:1081 the GPI anchor 1068:1081 The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. 7514386 12 65 theme first 1678:1682 arg1 analysis 1693:1700 the first detailed analysis 1674:1700 the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein 1674:1776 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 5 66 theme protein 614:620 arg1 mole 606:609 mole 606:609 mole of protein 606:620 Purified U-CD59 released 1 mol of inositol per mole of protein by nitrous acid deamination, which cleaved between glucosamine and inositol present commonly in the GPI anchor. 7514386 10 67 theme U-CD59 1346:1351 arg1 chains 1336:1341 the asparagine-linked sugar chains 1308:1341 the asparagine-linked sugar chains of U-CD59 1308:1351 The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. 7514386 5 68 theme nitrous 625:631 arg1 deamination 638:648 nitrous acid deamination 625:648 nitrous acid deamination 625:648 Purified U-CD59 released 1 mol of inositol per mole of protein by nitrous acid deamination, which cleaved between glucosamine and inositol present commonly in the GPI anchor. 7514386 5 69 theme acid 633:636 arg1 deamination 638:648 nitrous acid deamination 625:648 nitrous acid deamination 625:648 Purified U-CD59 released 1 mol of inositol per mole of protein by nitrous acid deamination, which cleaved between glucosamine and inositol present commonly in the GPI anchor. 7514386 4 70 from urine 527:531 arg1 U-CD59 534:539 U-CD59 534:539 U-CD59 534:539 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 4 70 from urine 527:531 arg1 form 511:514 a soluble form 501:514 a soluble form of CD59 in urine 501:531 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 5 71 theme inositol 593:600 arg1 mol 586:588 1 mol 584:588 1 mol of inositol per mole of protein 584:620 Purified U-CD59 released 1 mol of inositol per mole of protein by nitrous acid deamination, which cleaved between glucosamine and inositol present commonly in the GPI anchor. 7514386 2 72 theme important 208:216 arg1 attachment 252:261 its attachment 248:261 its attachment to the cell surface 248:281 An important structural feature of CD59 is its attachment to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor. 7514386 2 72 theme important 208:216 arg1 feature 229:235 An important structural feature 205:235 An important structural feature of CD59 205:243 An important structural feature of CD59 is its attachment to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor. 7514386 8 73 attach isolated 1088:1095 arg2 portion 1057:1063 the glycan portion 1046:1063 the glycan portion of the GPI anchor 1046:1081 The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. 7514386 8 73 attach isolated 1088:1095 arg1 peptides 1108:1115 these peptides 1102:1115 these peptides 1102:1115 The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. 7514386 8 73 attach isolated 1088:1095 arg2 chains 1035:1040 The asparagine-linked sugar chains 1007:1040 The asparagine-linked sugar chains 1007:1040 The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. 7514386 7 74 theme glycan 925:930 arg1 portion 932:938 a glycan portion 923:938 a glycan portion of the GPI anchor 923:956 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 12 75 theme protein 1770:1776 arg1 structure 1727:1735 the carboxyl-terminal structure 1705:1735 the carboxyl-terminal structure of the soluble-form GPI-anchored protein 1705:1776 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 0 76 theme sugar 87:91 arg1 chain 93:97 the asparagine-linked sugar chain 65:97 the asparagine-linked sugar chain 65:97 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 2 77 theme CD59 240:243 arg1 attachment 252:261 its attachment 248:261 its attachment to the cell surface 248:281 An important structural feature of CD59 is its attachment to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor. 7514386 2 77 theme CD59 240:243 arg1 feature 229:235 An important structural feature 205:235 An important structural feature of CD59 205:243 An important structural feature of CD59 is its attachment to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor. 7514386 12 78 theme human 1653:1657 arg1 anchor 1663:1668 the human GPI anchor 1649:1668 the human GPI anchor 1649:1668 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 4 79 theme GPI 449:451 arg1 anchor 453:458 the GPI anchor 445:458 the GPI anchor 445:458 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 13 80 theme phospholipase 2030:2042 arg1 D 2044:2044 glycan-phosphatidylinositol-specific phospholipase D 1993:2044 glycan-phosphatidylinositol-specific phospholipase D 1993:2044 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 7 81 theme sugar 884:888 arg1 chain 890:894 an asparagine-linked sugar chain 863:894 an asparagine-linked sugar chain 863:894 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 12 82 theme first 1611:1615 arg1 This 1599:1602 This 1599:1602 This 1599:1602 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 12 82 theme first 1611:1615 arg1 analysis 1637:1644 the first detailed structural analysis 1607:1644 the first detailed structural analysis of the human GPI anchor 1607:1668 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 0 83 from study 11:15 arg1 chain 93:97 the asparagine-linked sugar chain 65:97 the asparagine-linked sugar chain 65:97 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 0 83 from study 11:15 arg1 anchor 54:59 the glycosyl-phosphatidylinositol anchor 20:59 the glycosyl-phosphatidylinositol anchor 20:59 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 13 84 theme anchor 1839:1844 arg1 structure 1818:1826 the backbone structure 1805:1826 the backbone structure of the GPI anchor 1805:1844 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 0 85 theme soluble 104:110 arg1 form 112:115 a soluble form 102:115 a soluble form of CD59 102:123 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 12 86 theme structural 1626:1635 arg1 This 1599:1602 This 1599:1602 This 1599:1602 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 12 86 theme structural 1626:1635 arg1 analysis 1637:1644 the first detailed structural analysis 1607:1644 the first detailed structural analysis of the human GPI anchor 1607:1668 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 4 87 from CD59 519:522 arg1 urine 527:531 urine 527:531 urine 527:531 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 9 88 theme sequential 1228:1237 arg1 digestion 1254:1262 sequential exoglycosidase digestion 1228:1262 sequential exoglycosidase digestion 1228:1262 Their structures were analyzed by sequential exoglycosidase digestion and methylation analyses. 7514386 13 89 theme GPI 1835:1837 arg1 anchor 1839:1844 the GPI anchor 1831:1844 the GPI anchor 1831:1844 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 0 90 from anchor 54:59 arg1 urine 134:138 human urine 128:138 human urine 128:138 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 4 91 from form 511:514 arg1 urine 527:531 urine 527:531 urine 527:531 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 7 92 theme GPI 947:949 arg1 anchor 951:956 the GPI anchor 943:956 the GPI anchor 943:956 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 9 93 theme methylation 1268:1278 arg1 analyses 1280:1287 methylation analyses 1268:1287 methylation analyses 1268:1287 Their structures were analyzed by sequential exoglycosidase digestion and methylation analyses. 7514386 3 94 theme GPI-anchored 349:360 arg1 proteins 362:369 many GPI-anchored proteins 344:369 many GPI-anchored proteins 344:369 CD59, like many GPI-anchored proteins, has been found in urine, serum, and other body fluids. 7514386 4 95 theme form 511:514 arg1 structures 431:440 The structures 427:440 The structures of the GPI anchor 427:458 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 4 95 theme form 511:514 arg1 chain 492:496 the asparagine-linked sugar chain 464:496 the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, 464:540 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 3 96 located found 381:385 arg1 serum 397:401 serum 397:401 serum 397:401 CD59, like many GPI-anchored proteins, has been found in urine, serum, and other body fluids. 7514386 3 96 located found 381:385 arg2 CD59 333:336 CD59 333:336 CD59 333:336 CD59, like many GPI-anchored proteins, has been found in urine, serum, and other body fluids. 7514386 3 96 located found 381:385 arg1 urine 390:394 urine 390:394 urine 390:394 CD59, like many GPI-anchored proteins, has been found in urine, serum, and other body fluids. 7514386 3 96 located found 381:385 arg1 fluids 419:424 other body fluids 408:424 other body fluids 408:424 CD59, like many GPI-anchored proteins, has been found in urine, serum, and other body fluids. 7514386 4 97 theme asparagine-linked 468:484 arg1 chain 492:496 the asparagine-linked sugar chain 464:496 the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, 464:540 The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. 7514386 3 98 theme other 408:412 arg1 fluids 419:424 other body fluids 408:424 other body fluids 408:424 CD59, like many GPI-anchored proteins, has been found in urine, serum, and other body fluids. 7514386 12 99 theme soluble-form 1744:1755 arg1 protein 1770:1776 the soluble-form GPI-anchored protein 1740:1776 the soluble-form GPI-anchored protein 1740:1776 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 7 100 theme anchor 951:956 arg1 portion 932:938 a glycan portion 923:938 a glycan portion of the GPI anchor 923:956 The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. 7514386 11 101 theme variant 1507:1513 arg1 glycoprotein 1523:1534 Try-panosoma brucei variant surface glycoprotein 1487:1534 Try-panosoma brucei variant surface glycoprotein 1487:1534 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 8 102 theme asparagine-linked 1011:1027 arg1 chains 1035:1040 The asparagine-linked sugar chains 1007:1040 The asparagine-linked sugar chains 1007:1040 The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. 7514386 0 103 link asparagine-linked 69:85 arg1 chain 93:97 the asparagine-linked sugar chain 65:97 the asparagine-linked sugar chain 65:97 Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 7514386 11 104 theme significant 1548:1558 arg1 variations 1560:1569 significant variations 1548:1569 significant variations in its side-chain moieties 1548:1596 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 12 105 theme carboxyl-terminal 1709:1725 arg1 structure 1727:1735 the carboxyl-terminal structure 1705:1735 the carboxyl-terminal structure of the soluble-form GPI-anchored protein 1705:1776 This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. 7514386 11 106 theme side-chain 1578:1587 arg1 moieties 1589:1596 its side-chain moieties 1574:1596 its side-chain moieties 1574:1596 The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. 7514386 13 107 theme GPI-anchored 1928:1939 arg1 protein 1941:1947 the soluble-form GPI-anchored protein 1911:1947 the soluble-form GPI-anchored protein 1911:1947 The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D. 7514386 5 108 theme GPI 722:724 arg1 anchor 726:731 the GPI anchor 718:731 the GPI anchor 718:731 Purified U-CD59 released 1 mol of inositol per mole of protein by nitrous acid deamination, which cleaved between glucosamine and inositol present commonly in the GPI anchor. 8462541 5 0 theme B 1285:1285 arg1 chain 1287:1291 the A or B chain 1276:1291 the A or B chain of K2tu-PA 1276:1302 In addition, glycopeptide fragments corresponding with the A or B chain of K2tu-PA were analysed. 8462541 8 1 theme different 1593:1601 arg1 batches 1622:1628 different K2tu-PA production batches 1593:1628 different K2tu-PA production batches 1593:1628 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 3 2 gly tetrasialylated 899:913 arg1 % 934:934 18% 932:934 18% 932:934 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 3 2 gly tetrasialylated 899:913 arg1 structures 937:946 tetrasialylated tetra-antennary (18%) structures 899:946 tetrasialylated tetra-antennary (18%) structures 899:946 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 4 3 theme N-acetyl-9-O-acetylneuraminic 1180:1208 arg1 acid 1210:1213 N-acetyl-9-O-acetylneuraminic acid 1180:1213 N-acetyl-9-O-acetylneuraminic acid (3%) 1180:1218 Sialic acid occurred exclusively in alpha(2-3)-linkage to galactose, and consisted of N-acetylneuraminic acid (94%), N-glycolylneuraminic acid (3%), and N-acetyl-9-O-acetylneuraminic acid (3%). 8462541 4 3 theme N-acetyl-9-O-acetylneuraminic 1180:1208 arg1 % 1217:1217 3% 1216:1217 3% 1216:1217 Sialic acid occurred exclusively in alpha(2-3)-linkage to galactose, and consisted of N-acetylneuraminic acid (94%), N-glycolylneuraminic acid (3%), and N-acetyl-9-O-acetylneuraminic acid (3%). 8462541 8 4 theme glycoprotein 1792:1803 arg1 procedure 1766:1774 the applied isolation procedure 1744:1774 the applied isolation procedure of the chimeric glycoprotein 1744:1803 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 8 5 theme production 1611:1620 arg1 batches 1622:1628 different K2tu-PA production batches 1593:1628 different K2tu-PA production batches 1593:1628 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 1 6 theme hybrid 184:189 arg1 K2tu-PA 199:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 5 7 gly glycopeptide 1234:1245 arg2 glycopeptide 1234:1245 glycopeptide 1234:1245 glycopeptide 1234:1245 In addition, glycopeptide fragments corresponding with the A or B chain of K2tu-PA were analysed. 8462541 5 8 theme A 1280:1280 arg1 chain 1287:1291 the A or B chain 1276:1291 the A or B chain of K2tu-PA 1276:1302 In addition, glycopeptide fragments corresponding with the A or B chain of K2tu-PA were analysed. 8462541 7 9 theme different 1511:1519 arg1 sources 1532:1538 different biological sources 1511:1538 different biological sources 1511:1538 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 7 10 gly glycosylation 1426:1438 arg1 K2tu-PA 1451:1457 K2tu-PA 1451:1457 K2tu-PA 1451:1457 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 0 11 theme hamster 121:127 arg1 cells 135:139 Chinese hamster ovary cells 113:139 Chinese hamster ovary cells 113:139 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 1 12 theme Chinese 221:227 arg1 cells 243:247 Chinese hamster ovary cells 221:247 Chinese hamster ovary cells 221:247 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 7 13 theme tissue-type 1472:1482 arg1 activator 1496:1504 tissue-type plasminogen activator 1472:1504 tissue-type plasminogen activator from different biological sources 1472:1538 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 3 14 gly disialylated 775:786 arg1 diantennary 788:798 disialylated diantennary 775:798 disialylated diantennary (45%) 775:804 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 3 14 gly disialylated 775:786 arg1 % 803:803 45% 801:803 45% 801:803 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 2 15 theme 500-MHz 669:675 arg1 spectroscopy 684:695 500-MHz 1H-NMR spectroscopy 669:695 500-MHz 1H-NMR spectroscopy 669:695 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 8 16 theme oligosaccharides 1675:1690 arg1 identical 1697:1705 identical 1697:1705 identical 1697:1705 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 8 16 theme oligosaccharides 1675:1690 arg1 structures 1652:1661 the structures 1648:1661 the structures of N-linked oligosaccharides 1648:1690 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 8 17 theme applied 1748:1754 arg1 procedure 1766:1774 the applied isolation procedure 1744:1774 the applied isolation procedure of the chimeric glycoprotein 1744:1803 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 2 18 theme gel 549:551 arg1 chromatography 564:577 gel permeation chromatography 549:577 gel permeation chromatography 549:577 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 3 19 gly trisialylated 850:862 arg1 tri- 864:867 trisialylated tri- 850:867 trisialylated tri- 850:867 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 2 20 from HPLC 629:632 arg1 Lichrosorb-NH2 637:650 Lichrosorb-NH2 637:650 Lichrosorb-NH2 637:650 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 7 21 theme K2tu-PA 1451:1457 arg1 pattern 1440:1446 the glycosylation pattern 1422:1446 the glycosylation pattern of K2tu-PA 1422:1457 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 0 22 theme human 55:59 arg1 activator 82:90 a human chimeric plasminogen activator 53:90 a human chimeric plasminogen activator K2tu-PA 53:98 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 1 23 theme recombinant 144:154 arg1 K2tu-PA 199:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 7 24 theme pattern 1440:1446 arg1 Comparison 1408:1417 Comparison 1408:1417 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources 1408:1538 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 2 25 theme asparagine 471:480 arg1 F 490:490 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 432:490 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 432:490 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 0 26 theme plasminogen 70:80 arg1 activator 82:90 a human chimeric plasminogen activator 53:90 a human chimeric plasminogen activator K2tu-PA 53:98 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 8 27 theme relative 1717:1724 arg1 amounts 1726:1732 relative amounts 1717:1732 relative amounts 1717:1732 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 1 28 theme plasminogen 162:172 arg1 K2tu-PA 199:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 4 29 theme N-acetylneuraminic 1113:1130 arg1 acid 1132:1135 N-acetylneuraminic acid 1113:1135 N-acetylneuraminic acid (94%) 1113:1141 Sialic acid occurred exclusively in alpha(2-3)-linkage to galactose, and consisted of N-acetylneuraminic acid (94%), N-glycolylneuraminic acid (3%), and N-acetyl-9-O-acetylneuraminic acid (3%). 8462541 4 29 theme N-acetylneuraminic 1113:1130 arg1 % 1140:1140 94% 1138:1140 94% 1138:1140 Sialic acid occurred exclusively in alpha(2-3)-linkage to galactose, and consisted of N-acetylneuraminic acid (94%), N-glycolylneuraminic acid (3%), and N-acetyl-9-O-acetylneuraminic acid (3%). 8462541 3 30 theme disialylated 775:786 arg1 diantennary 788:798 disialylated diantennary 775:798 disialylated diantennary (45%) 775:804 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 3 30 theme disialylated 775:786 arg1 % 803:803 45% 801:803 45% 801:803 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 0 31 theme K2tu-PA 92:98 arg1 chains 43:48 N-linked carbohydrate chains 21:48 N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA 21:98 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 3 32 theme trisialylated 850:862 arg1 tri- 864:867 trisialylated tri- 850:867 trisialylated tri- 850:867 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 1 33 theme B 352:352 arg1 domain 370:375 protease domain 361:375 protease domain 361:375 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 1 33 theme B 352:352 arg1 chain 354:358 B chain 352:358 B chain 352:358 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 2 34 theme chains 422:427 arg1 release 385:391 release 385:391 release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 385:490 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 8 35 from studies 1582:1588 arg1 batches 1622:1628 different K2tu-PA production batches 1593:1628 different K2tu-PA production batches 1593:1628 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 0 36 theme Primary 0:6 arg1 structure 8:16 Primary structure 0:16 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA 0:98 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 8 37 theme isolation 1756:1764 arg1 procedure 1766:1774 the applied isolation procedure 1744:1774 the applied isolation procedure of the chimeric glycoprotein 1744:1803 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 2 38 theme N-linked 400:407 arg1 chains 422:427 the N-linked carbohydrate chains 396:427 the N-linked carbohydrate chains 396:427 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 7 39 theme biological 1521:1530 arg1 sources 1532:1538 different biological sources 1511:1538 different biological sources 1511:1538 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 2 40 theme N-acetyl-beta-glucosaminyl 444:469 arg1 F 490:490 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 432:490 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 432:490 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 4 41 theme Sialic 1027:1032 arg1 acid 1034:1037 Sialic acid 1027:1037 Sialic acid 1027:1037 Sialic acid occurred exclusively in alpha(2-3)-linkage to galactose, and consisted of N-acetylneuraminic acid (94%), N-glycolylneuraminic acid (3%), and N-acetyl-9-O-acetylneuraminic acid (3%). 8462541 0 42 theme carbohydrate 30:41 arg1 chains 43:48 N-linked carbohydrate chains 21:48 N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA 21:98 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 3 43 theme Asn-bound 996:1004 arg1 N-acetylglucosamine 1006:1024 the Asn-bound N-acetylglucosamine 992:1024 the Asn-bound N-acetylglucosamine 992:1024 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 2 44 theme peptide-N4- 432:442 arg1 F 490:490 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 432:490 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 432:490 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 5 45 theme glycopeptide 1234:1245 arg1 fragments 1247:1255 glycopeptide fragments 1234:1255 glycopeptide fragments corresponding with the A or B chain of K2tu-PA 1234:1302 In addition, glycopeptide fragments corresponding with the A or B chain of K2tu-PA were analysed. 8462541 1 46 theme hamster 229:235 arg1 cells 243:247 Chinese hamster ovary cells 221:247 Chinese hamster ovary cells 221:247 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 3 47 theme tetrasialylated 899:913 arg1 % 934:934 18% 932:934 18% 932:934 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 3 47 theme tetrasialylated 899:913 arg1 structures 937:946 tetrasialylated tetra-antennary (18%) structures 899:946 tetrasialylated tetra-antennary (18%) structures 899:946 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 8 48 link N-linked 1666:1673 arg1 oligosaccharides 1675:1690 N-linked oligosaccharides 1666:1690 N-linked oligosaccharides 1666:1690 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 8 49 gly glycoprotein 1792:1803 arg1 glycoprotein 1792:1803 the chimeric glycoprotein 1779:1803 the chimeric glycoprotein 1779:1803 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 0 50 link N-linked 21:28 arg1 chains 43:48 N-linked carbohydrate chains 21:48 N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA 21:98 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 8 51 theme chimeric 1783:1790 arg1 glycoprotein 1792:1803 the chimeric glycoprotein 1779:1803 the chimeric glycoprotein 1779:1803 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 8 52 theme Profiling 1572:1580 arg1 studies 1582:1588 Profiling studies 1572:1588 Profiling studies on different K2tu-PA production batches 1572:1628 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 8 53 theme K2tu-PA 1603:1609 arg1 batches 1622:1628 different K2tu-PA production batches 1593:1628 different K2tu-PA production batches 1593:1628 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 3 54 theme following 702:710 arg1 types 712:716 The following types 698:716 The following types of carbohydrates 698:733 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 5 55 theme K2tu-PA 1296:1302 arg1 chain 1287:1291 the A or B chain 1276:1291 the A or B chain of K2tu-PA 1276:1302 In addition, glycopeptide fragments corresponding with the A or B chain of K2tu-PA were analysed. 8462541 1 56 theme activator 174:182 arg1 K2tu-PA 199:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 2 57 theme Mono 609:612 arg1 Q 614:614 Mono Q 609:614 Mono Q 609:614 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 3 58 theme carbohydrates 721:733 arg1 types 712:716 The following types 698:716 The following types of carbohydrates 698:733 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 1 59 gly glycosylated 328:339 arg1 K2tu-PA 199:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 1 59 gly glycosylated 328:339 arg2 Asn247 344:349 Asn247 344:349 Asn247 (B chain, protease domain) 344:376 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 1 60 theme variant 191:197 arg1 K2tu-PA 199:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 3 61 gly monosialylated 742:755 arg1 diantennary 757:767 monosialylated diantennary 742:767 monosialylated diantennary (8%) 742:772 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 3 61 gly monosialylated 742:755 arg1 % 771:771 8% 770:771 8% 770:771 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 6 62 attach attached 1388:1395 arg2 those 1382:1386 those 1382:1386 those 1382:1386 The oligosaccharides attached to Asn12 are less processed than those attached to Asn247. 8462541 6 62 attach attached 1388:1395 arg1 Asn247 1400:1405 Asn247 1400:1405 Asn247 1400:1405 The oligosaccharides attached to Asn12 are less processed than those attached to Asn247. 8462541 0 63 theme ovary 129:133 arg1 cells 135:139 Chinese hamster ovary cells 113:139 Chinese hamster ovary cells 113:139 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 7 64 theme plasminogen 1484:1494 arg1 activator 1496:1504 tissue-type plasminogen activator 1472:1504 tissue-type plasminogen activator from different biological sources 1472:1538 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 1 65 theme protease 361:368 arg1 domain 370:375 protease domain 361:375 protease domain 361:375 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 1 65 theme protease 361:368 arg1 chain 354:358 B chain 352:358 B chain 352:358 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 7 66 from sources 1532:1538 arg1 activator 1496:1504 tissue-type plasminogen activator 1472:1504 tissue-type plasminogen activator from different biological sources 1472:1538 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 2 67 theme 1H-NMR 677:682 arg1 spectroscopy 684:695 500-MHz 1H-NMR spectroscopy 669:695 500-MHz 1H-NMR spectroscopy 669:695 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 7 68 with Comparison 1408:1417 arg1 that 1464:1467 that 1464:1467 that 1464:1467 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 2 69 theme permeation 553:562 arg1 chromatography 564:577 gel permeation chromatography 549:577 gel permeation chromatography 549:577 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 3 70 theme monosialylated 742:755 arg1 diantennary 757:767 monosialylated diantennary 742:767 monosialylated diantennary (8%) 742:772 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 3 70 theme monosialylated 742:755 arg1 % 771:771 8% 770:771 8% 770:771 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 8 71 theme N-linked 1666:1673 arg1 oligosaccharides 1675:1690 N-linked oligosaccharides 1666:1690 N-linked oligosaccharides 1666:1690 Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. 8462541 3 72 theme disialylated 807:818 arg1 % 846:846 1% 845:846 1% 845:846 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 3 72 theme disialylated 807:818 arg1 tri- 820:823 disialylated tri- 807:823 disialylated tri- 807:823 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 6 73 attach attached 1340:1347 arg2 oligosaccharides 1323:1338 The oligosaccharides 1319:1338 The oligosaccharides attached to Asn12 1319:1356 The oligosaccharides attached to Asn12 are less processed than those attached to Asn247. 8462541 6 73 attach attached 1340:1347 arg1 Asn12 1352:1356 Asn12 1352:1356 Asn12 1352:1356 The oligosaccharides attached to Asn12 are less processed than those attached to Asn247. 8462541 4 74 theme alpha 1063:1067 arg1 -linkage 1073:1080 alpha(2-3)-linkage 1063:1080 alpha(2-3)-linkage to galactose 1063:1093 Sialic acid occurred exclusively in alpha(2-3)-linkage to galactose, and consisted of N-acetylneuraminic acid (94%), N-glycolylneuraminic acid (3%), and N-acetyl-9-O-acetylneuraminic acid (3%). 8462541 0 75 theme chimeric 61:68 arg1 activator 82:90 a human chimeric plasminogen activator 53:90 a human chimeric plasminogen activator K2tu-PA 53:98 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 7 76 theme glycosylation 1426:1438 arg1 pattern 1440:1446 the glycosylation pattern 1422:1446 the glycosylation pattern of K2tu-PA 1422:1457 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 2 77 theme amidase 482:488 arg1 F 490:490 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 432:490 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 432:490 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 4 78 theme 2-3 1069:1071 arg1 -linkage 1073:1080 alpha(2-3)-linkage 1063:1080 alpha(2-3)-linkage to galactose 1063:1093 Sialic acid occurred exclusively in alpha(2-3)-linkage to galactose, and consisted of N-acetylneuraminic acid (94%), N-glycolylneuraminic acid (3%), and N-acetyl-9-O-acetylneuraminic acid (3%). 8462541 0 79 theme activator 82:90 arg1 K2tu-PA 92:98 a human chimeric plasminogen activator K2tu-PA 53:98 a human chimeric plasminogen activator K2tu-PA 53:98 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 3 80 theme alpha 970:974 arg1 -linkage 980:987 alpha(1-6)-linkage 970:987 alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine 970:1024 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 1 81 theme human 156:160 arg1 K2tu-PA 199:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 1 82 dep Asn12 279:283 arg1 chain 288:292 A chain 286:292 A chain 286:292 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 1 82 dep Asn12 279:283 arg1 domain 305:310 kringle-2 domain 295:310 kringle-2 domain 295:310 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 2 83 link N-linked 400:407 arg1 chains 422:427 the N-linked carbohydrate chains 396:427 the N-linked carbohydrate chains 396:427 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 3 84 from N-acetylglucosamine 1006:1024 arg1 -linkage 980:987 alpha(1-6)-linkage 970:987 alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine 970:1024 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 0 85 theme Chinese 113:119 arg1 cells 135:139 Chinese hamster ovary cells 113:139 Chinese hamster ovary cells 113:139 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 3 86 gly disialylated 807:818 arg1 % 846:846 1% 845:846 1% 845:846 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 3 86 gly disialylated 807:818 arg1 tri- 820:823 disialylated tri- 807:823 disialylated tri- 807:823 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 2 87 theme carbohydrate 409:420 arg1 chains 422:427 the N-linked carbohydrate chains 396:427 the N-linked carbohydrate chains 396:427 After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. 8462541 0 88 theme N-linked 21:28 arg1 chains 43:48 N-linked carbohydrate chains 21:48 N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA 21:98 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 1 89 gly glycosylated 263:274 arg2 Asn12 279:283 Asn12 279:283 Asn12 (A chain, kringle-2 domain) 279:311 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 1 89 gly glycosylated 263:274 arg1 K2tu-PA 199:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA 142:205 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 7 90 theme significant 1547:1557 arg1 differences 1559:1569 significant differences 1547:1569 significant differences 1547:1569 Comparison of the glycosylation pattern of K2tu-PA with that of tissue-type plasminogen activator from different biological sources showed significant differences. 8462541 0 91 theme chains 43:48 arg1 structure 8:16 Primary structure 0:16 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA 0:98 Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. 8462541 1 92 theme kringle-2 295:303 arg1 chain 288:292 A chain 286:292 A chain 286:292 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 1 92 theme kringle-2 295:303 arg1 domain 305:310 kringle-2 domain 295:310 kringle-2 domain 295:310 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 1 93 dep Asn247 344:349 arg1 domain 370:375 protease domain 361:375 protease domain 361:375 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 1 93 dep Asn247 344:349 arg1 chain 354:358 B chain 352:358 B chain 352:358 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 4 94 theme N-glycolylneuraminic 1144:1163 arg1 acid 1165:1168 N-glycolylneuraminic acid 1144:1168 N-glycolylneuraminic acid (3%) 1144:1173 Sialic acid occurred exclusively in alpha(2-3)-linkage to galactose, and consisted of N-acetylneuraminic acid (94%), N-glycolylneuraminic acid (3%), and N-acetyl-9-O-acetylneuraminic acid (3%). 8462541 4 94 theme N-glycolylneuraminic 1144:1163 arg1 % 1172:1172 3% 1171:1172 3% 1171:1172 Sialic acid occurred exclusively in alpha(2-3)-linkage to galactose, and consisted of N-acetylneuraminic acid (94%), N-glycolylneuraminic acid (3%), and N-acetyl-9-O-acetylneuraminic acid (3%). 8462541 1 95 theme ovary 237:241 arg1 cells 243:247 Chinese hamster ovary cells 221:247 Chinese hamster ovary cells 221:247 A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle-2 domain) and completely glycosylated at Asn247 (B chain, protease domain). 8462541 3 96 theme tetra-antennary 915:929 arg1 % 934:934 18% 932:934 18% 932:934 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 8462541 3 96 theme tetra-antennary 915:929 arg1 structures 937:946 tetrasialylated tetra-antennary (18%) structures 899:946 tetrasialylated tetra-antennary (18%) structures 899:946 The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N-acetylglucosamine. 6501316 1 0 theme oligosaccharide 287:301 arg1 alditols 303:310 neutral (79.7%) and acidic (20.3%) oligosaccharide alditols 252:310 neutral (79.7%) and acidic (20.3%) oligosaccharide alditols 252:310 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 1 1 theme gastric 155:161 arg1 aspirates 163:171 gastric aspirates 155:171 gastric aspirates of the secretors with blood group A 155:207 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 2 2 theme oligosaccharide 413:427 arg1 fraction 429:436 the neutral oligosaccharide fraction 401:436 the neutral oligosaccharide fraction 401:436 Nine oligosaccharides (I-IX), ranging from 6 to 15 sugar units, have been purified from the neutral oligosaccharide fraction. 6501316 1 3 theme alditols 303:310 arg1 population 238:247 a heterogeneous population 222:247 a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols 222:310 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 1 4 theme neutral 252:258 arg1 alditols 303:310 neutral (79.7%) and acidic (20.3%) oligosaccharide alditols 252:310 neutral (79.7%) and acidic (20.3%) oligosaccharide alditols 252:310 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 3 5 theme degradation 504:514 arg1 results 452:458 the results 448:458 the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses 448:570 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 3 6 theme sugar 485:489 arg1 composition 491:501 sugar composition 485:501 sugar composition 485:501 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 3 7 theme immunological 463:475 arg1 assays 477:482 immunological assays 463:482 immunological assays 463:482 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 1 8 dep acidic 272:277 arg1 % 284:284 20.3% 280:284 20.3% 280:284 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 3 9 theme assays 477:482 arg1 results 452:458 the results 448:458 the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses 448:570 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 3 10 with composition 491:501 arg1 exoglycosidases 530:544 specific exoglycosidases 521:544 specific exoglycosidases 521:544 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 1 11 theme Alkaline 87:94 arg1 cleavage 118:125 Alkaline borohydride reductive cleavage 87:125 Alkaline borohydride reductive cleavage 87:125 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 1 12 theme secretors 180:188 arg1 aspirates 163:171 gastric aspirates 155:171 gastric aspirates of the secretors with blood group A 155:207 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 3 13 with assays 477:482 arg1 exoglycosidases 530:544 specific exoglycosidases 521:544 specific exoglycosidases 521:544 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 1 14 theme borohydride 96:106 arg1 cleavage 118:125 Alkaline borohydride reductive cleavage 87:125 Alkaline borohydride reductive cleavage 87:125 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 0 15 theme neutral 18:24 arg1 oligosaccharides 26:41 the neutral oligosaccharides 14:41 the neutral oligosaccharides 14:41 Structures of the neutral oligosaccharides isolated from A-active human gastric mucin. 6501316 1 16 theme reductive 108:116 arg1 cleavage 118:125 Alkaline borohydride reductive cleavage 87:125 Alkaline borohydride reductive cleavage 87:125 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 1 17 theme blood 195:199 arg1 A 207:207 blood group A 195:207 blood group A 195:207 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 3 18 theme following 588:596 arg1 structures 598:607 the following structures 584:607 the following structures for these oligosaccharides 584:634 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 1 19 theme group 201:205 arg1 A 207:207 blood group A 195:207 blood group A 195:207 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 2 20 theme neutral 405:411 arg1 fraction 429:436 the neutral oligosaccharide fraction 401:436 the neutral oligosaccharide fraction 401:436 Nine oligosaccharides (I-IX), ranging from 6 to 15 sugar units, have been purified from the neutral oligosaccharide fraction. 6501316 0 21 theme oligosaccharides 26:41 arg1 Structures 0:9 Structures 0:9 Structures of the neutral oligosaccharides 0:41 Structures of the neutral oligosaccharides isolated from A-active human gastric mucin. 6501316 1 22 theme acidic 272:277 arg1 alditols 303:310 neutral (79.7%) and acidic (20.3%) oligosaccharide alditols 252:310 neutral (79.7%) and acidic (20.3%) oligosaccharide alditols 252:310 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 3 23 from sequence 638:645 arg1 text 650:653 text 650:653 text 650:653 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 3 24 with degradation 504:514 arg1 exoglycosidases 530:544 specific exoglycosidases 521:544 specific exoglycosidases 521:544 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 0 25 theme A-active 57:64 arg1 mucin 80:84 A-active human gastric mucin 57:84 A-active human gastric mucin 57:84 Structures of the neutral oligosaccharides isolated from A-active human gastric mucin. 6501316 1 26 with secretors 180:188 arg1 A 207:207 blood group A 195:207 blood group A 195:207 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 3 27 with analyses 563:570 arg1 exoglycosidases 530:544 specific exoglycosidases 521:544 specific exoglycosidases 521:544 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 3 28 theme specific 521:528 arg1 exoglycosidases 530:544 specific exoglycosidases 521:544 specific exoglycosidases 521:544 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 1 29 dep neutral 252:258 arg1 % 265:265 79.7% 261:265 79.7% 261:265 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 2 30 dep 15 361:362 arg1 to 358:359 to 358:359 to 358:359 Nine oligosaccharides (I-IX), ranging from 6 to 15 sugar units, have been purified from the neutral oligosaccharide fraction. 6501316 1 31 theme mucin 134:138 arg1 cleavage 118:125 Alkaline borohydride reductive cleavage 87:125 Alkaline borohydride reductive cleavage 87:125 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 6501316 3 32 theme composition 491:501 arg1 results 452:458 the results 448:458 the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses 448:570 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 0 33 theme gastric 72:78 arg1 mucin 80:84 A-active human gastric mucin 57:84 A-active human gastric mucin 57:84 Structures of the neutral oligosaccharides isolated from A-active human gastric mucin. 6501316 3 34 theme methylation 551:561 arg1 analyses 563:570 methylation analyses 551:570 methylation analyses 551:570 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 2 35 theme sugar 364:368 arg1 units 370:374 6 to 15 sugar units 356:374 6 to 15 sugar units 356:374 Nine oligosaccharides (I-IX), ranging from 6 to 15 sugar units, have been purified from the neutral oligosaccharide fraction. 6501316 0 36 theme human 66:70 arg1 mucin 80:84 A-active human gastric mucin 57:84 A-active human gastric mucin 57:84 Structures of the neutral oligosaccharides isolated from A-active human gastric mucin. 6501316 3 37 theme analyses 563:570 arg1 results 452:458 the results 448:458 the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses 448:570 Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text) 6501316 1 38 theme heterogeneous 224:236 arg1 population 238:247 a heterogeneous population 222:247 a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols 222:310 Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. 8390218 2 0 theme biantennary 634:644 arg1 chain 652:656 the biantennary sugar chain 630:656 the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, 630:859 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 1 with patients 216:223 arg1 HCC 256:258 HCC 256:258 HCC 256:258 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 1 with patients 216:223 arg1 carcinoma 245:253 hepatocellular carcinoma 230:253 hepatocellular carcinoma (HCC) 230:259 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 2 2 theme Fuc 836:838 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 2 theme Fuc 836:838 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 3 from patients 599:606 arg1 species 579:585 the LCA-reactive species 562:585 the LCA-reactive species of AAT from patients with HCC 562:615 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 4 4 from patients 1363:1370 arg1 chains 1344:1349 the carbohydrate chains 1327:1349 the carbohydrate chains of AAT from patients with HCC 1327:1379 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 4 4 from patients 1363:1370 arg1 increment 1387:1395 an increment 1384:1395 an increment in fucosylation 1384:1411 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 4 4 from patients 1363:1370 arg1 feature 1316:1322 a characteristic feature 1299:1322 a characteristic feature of the carbohydrate chains of AAT from patients with HCC 1299:1379 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 1 5 theme exoglycosidase 425:438 arg1 digestion 440:448 stepwise exoglycosidase digestion 416:448 stepwise exoglycosidase digestion 416:448 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 3 6 theme 1-4GlcNAc 1142:1150 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 6 theme 1-4GlcNAc 1142:1150 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 7 theme Gal 1133:1135 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 7 theme Gal 1133:1135 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 8 theme 1-4GlcNAc 776:784 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 8 theme 1-4GlcNAc 776:784 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 9 from individuals 278:288 arg1 structures 151:160 Chemical structures 142:160 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) 142:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 9 from individuals 278:288 arg1 chains 175:180 the sugar chains 165:180 the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) 165:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 10 theme chains 175:180 arg1 structures 151:160 Chemical structures 142:160 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) 142:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 3 11 theme 1-6 1170:1172 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 11 theme 1-6 1170:1172 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 1 12 with individuals 278:288 arg1 affinity 307:314 a different affinity 295:314 a different affinity for Lens culinaris agglutinin (LCA) 295:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 2 13 theme Gal 767:769 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 13 theme Gal 767:769 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 3 14 theme 1-2Man 1198:1203 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 14 theme 1-2Man 1198:1203 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 15 with chain 652:656 arg1 residue 672:678 a fucose residue 663:678 a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, 663:859 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 16 theme alpha 185:189 arg1 AAT 206:208 AAT 206:208 AAT 206:208 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 16 theme alpha 185:189 arg1 1-antitrypsin 191:203 alpha 1-antitrypsin 185:203 alpha 1-antitrypsin (AAT) 185:209 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 3 17 theme 1-2Man 1157:1162 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 17 theme 1-2Man 1157:1162 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 18 theme AAT 590:592 arg1 species 579:585 the LCA-reactive species 562:585 the LCA-reactive species of AAT from patients with HCC 562:615 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 3 19 theme 1-4GlcNAc 1224:1232 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 19 theme 1-4GlcNAc 1224:1232 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 4 20 from feature 1316:1322 arg1 patients 1363:1370 patients 1363:1370 patients with HCC 1363:1379 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 4 21 theme carbohydrate 1331:1342 arg1 chains 1344:1349 the carbohydrate chains 1327:1349 the carbohydrate chains of AAT from patients with HCC 1327:1379 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 3 22 theme 1-4GlcNAc 1183:1191 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 22 theme 1-4GlcNAc 1183:1191 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 23 theme 1-2Man 791:796 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 23 theme 1-2Man 791:796 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 3 24 theme Man 1215:1217 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 24 theme Man 1215:1217 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 25 theme Gal 1174:1176 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 25 theme Gal 1174:1176 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 26 theme beta 973:976 arg1 alpha 985:989 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 26 theme beta 973:976 arg1 alpha 944:948 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6 913:952 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 27 theme 1-4GlcNAc 735:743 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 27 theme 1-4GlcNAc 735:743 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 27 theme 1-4GlcNAc 735:743 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 4 28 theme characteristic 1301:1314 arg1 increment 1387:1395 an increment 1384:1395 an increment in fucosylation 1384:1411 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 4 28 theme characteristic 1301:1314 arg1 feature 1316:1322 a characteristic feature 1299:1322 a characteristic feature of the carbohydrate chains of AAT from patients with HCC 1299:1379 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 2 29 theme beta 999:1002 arg1 residue 904:910 a fucose residue 895:910 a fucose residue 895:910 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 29 theme beta 999:1002 arg1 1-4GlcNAc-PA 1019:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 30 theme Gal 726:728 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 30 theme Gal 726:728 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 30 theme Gal 726:728 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 31 from patients 216:223 arg1 structures 151:160 Chemical structures 142:160 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) 142:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 31 from patients 216:223 arg1 chains 175:180 the sugar chains 165:180 the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) 165:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 2 32 theme 1-6 763:765 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 32 theme 1-6 763:765 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 32 theme 1-6 763:765 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 0 33 theme alpha 49:53 arg1 1-antitrypsin 55:67 human alpha 1-antitrypsin 43:67 human alpha 1-antitrypsin 43:67 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 2 34 theme alpha 944:948 arg1 residue 904:910 a fucose residue 895:910 a fucose residue 895:910 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 34 theme alpha 944:948 arg1 1-4GlcNAc-PA 1019:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 35 theme 1-2Man 750:755 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 35 theme 1-2Man 750:755 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 35 theme 1-2Man 750:755 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 36 theme culinaris 325:333 arg1 LCA 347:349 LCA 347:349 LCA 347:349 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 36 theme culinaris 325:333 arg1 agglutinin 335:344 Lens culinaris agglutinin 320:344 Lens culinaris agglutinin (LCA) 320:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 2 37 theme beta 932:935 arg1 alpha 944:948 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6 913:952 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 37 theme beta 932:935 arg1 alpha 985:989 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 38 theme beta 958:961 arg1 alpha 985:989 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 38 theme beta 958:961 arg1 alpha 944:948 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6 913:952 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 39 theme fucose 665:670 arg1 residue 672:678 a fucose residue 663:678 a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, 663:859 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 0 40 theme biantennary 94:104 arg1 glycan 106:111 fucosylated biantennary glycan 82:111 fucosylated biantennary glycan 82:111 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 0 41 theme Structural 0:9 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis on the sugar chains of human alpha 1-antitrypsin 0:67 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 0 42 gly fucosylated 82:92 arg1 glycan 106:111 fucosylated biantennary glycan 82:111 fucosylated biantennary glycan 82:111 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 2 43 theme fucose 897:902 arg1 residue 904:910 a fucose residue 895:910 a fucose residue 895:910 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 43 theme fucose 897:902 arg1 1-4GlcNAc-PA 1019:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 44 theme innermost 687:695 arg1 GlcNAc-PA 850:858 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 44 theme innermost 687:695 arg1 residue 717:723 the innermost N-acetylglucosamine residue 683:723 the innermost N-acetylglucosamine residue 683:723 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 45 theme healthy 270:276 arg1 individuals 278:288 healthy individuals 270:288 healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) 270:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 3 46 theme LCA-nonreactive 1064:1078 arg1 species 1080:1086 The LCA-nonreactive species 1060:1086 The LCA-nonreactive species of AAT 1060:1093 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 0 47 theme sugar 27:31 arg1 chains 33:38 the sugar chains 23:38 the sugar chains of human alpha 1-antitrypsin 23:67 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 2 48 theme beta 917:920 arg1 beta 932:935 Gal beta 1-4GlcNAc beta 913:935 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 49 theme liquid 525:530 arg1 chromatography 532:545 high-performance liquid chromatography 508:545 high-performance liquid chromatography 508:545 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 50 theme different 297:305 arg1 affinity 307:314 a different affinity 295:314 a different affinity for Lens culinaris agglutinin (LCA) 295:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 2 51 theme beta 827:830 arg1 GlcNAc-PA 850:858 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 51 theme beta 827:830 arg1 residue 717:723 the innermost N-acetylglucosamine residue 683:723 the innermost N-acetylglucosamine residue 683:723 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 52 theme beta 812:815 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 52 theme beta 812:815 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 52 theme beta 812:815 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 3 53 contain contained 1095:1103 arg2 1-4GlcNAc 1239:1247 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 53 contain contained 1095:1103 arg2 component 1260:1268 a major component 1252:1268 a major component 1252:1268 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 53 contain contained 1095:1103 arg1 species 1080:1086 The LCA-nonreactive species 1060:1086 The LCA-nonreactive species of AAT 1060:1093 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 54 theme chain 1127:1131 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 54 theme chain 1127:1131 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 1 55 with combination 453:463 arg1 reversed-phase 470:483 reversed-phase 470:483 reversed-phase 470:483 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 55 with combination 453:463 arg1 size-fractionation 489:506 size-fractionation 489:506 size-fractionation 489:506 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 3 56 theme biantennary 1109:1119 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 56 theme biantennary 1109:1119 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 57 theme biantennary 869:879 arg1 chain 881:885 the biantennary chain 865:885 the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6 865:1057 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 58 theme digestion 440:448 arg1 pyridylamination 369:384 pyridylamination 369:384 pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion 369:448 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 3 59 theme beta 1152:1155 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 59 theme beta 1152:1155 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 60 theme beta 786:789 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 60 theme beta 786:789 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 61 theme sugar 169:173 arg1 chains 175:180 the sugar chains 165:180 the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) 165:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 3 62 theme beta 1137:1140 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 62 theme beta 1137:1140 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 63 theme beta 771:774 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 63 theme beta 771:774 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 64 theme 1-2Man 937:942 arg1 alpha 944:948 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6 913:952 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 64 theme 1-2Man 937:942 arg1 alpha 985:989 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 65 theme sugar 646:650 arg1 chain 652:656 the biantennary sugar chain 630:656 the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, 630:859 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 66 from ratio 1038:1042 arg1 residue 904:910 a fucose residue 895:910 a fucose residue 895:910 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 66 from ratio 1038:1042 arg1 1-4GlcNAc-PA 1019:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 0 67 theme hepatocellular 116:129 arg1 carcinoma 131:139 hepatocellular carcinoma 116:139 hepatocellular carcinoma 116:139 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 4 68 with patients 1363:1370 arg1 HCC 1377:1379 HCC 1377:1379 HCC 1377:1379 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 1 69 theme 1-antitrypsin 191:203 arg1 chains 175:180 the sugar chains 165:180 the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) 165:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 3 70 theme alpha 1164:1168 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 70 theme alpha 1164:1168 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 0 71 from presence 70:77 arg1 carcinoma 131:139 hepatocellular carcinoma 116:139 hepatocellular carcinoma 116:139 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 3 72 theme beta 1234:1237 arg1 1-4GlcNAc 1239:1247 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 72 theme beta 1234:1237 arg1 component 1260:1268 a major component 1252:1268 a major component 1252:1268 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 73 theme beta 1193:1196 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 73 theme beta 1193:1196 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 74 theme LCA-reactive 566:577 arg1 species 579:585 the LCA-reactive species 562:585 the LCA-reactive species of AAT from patients with HCC 562:615 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 75 theme 1-2Man 978:983 arg1 alpha 985:989 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 75 theme 1-2Man 978:983 arg1 alpha 944:948 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6 913:952 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 76 theme beta 745:748 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 76 theme beta 745:748 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 76 theme beta 745:748 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 3 77 theme beta 1219:1222 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 77 theme beta 1219:1222 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 78 theme beta 1178:1181 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 78 theme beta 1178:1181 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 79 theme 1-4GlcNAc 1004:1012 arg1 residue 904:910 a fucose residue 895:910 a fucose residue 895:910 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 79 theme 1-4GlcNAc 1004:1012 arg1 1-4GlcNAc-PA 1019:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 80 theme beta 730:733 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 80 theme beta 730:733 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 80 theme beta 730:733 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 3 81 theme major 1254:1258 arg1 1-4GlcNAc 1239:1247 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 81 theme major 1254:1258 arg1 component 1260:1268 a major component 1252:1268 a major component 1252:1268 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 82 contain carried 617:623 arg2 chain 881:885 the biantennary chain 865:885 the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6 865:1057 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 82 contain carried 617:623 arg2 chain 652:656 the biantennary sugar chain 630:656 the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, 630:859 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 82 contain carried 617:623 arg1 species 579:585 the LCA-reactive species 562:585 the LCA-reactive species of AAT from patients with HCC 562:615 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 83 theme oligosaccharides 395:410 arg1 pyridylamination 369:384 pyridylamination 369:384 pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion 369:448 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 2 84 theme Man 995:997 arg1 residue 904:910 a fucose residue 895:910 a fucose residue 895:910 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 84 theme Man 995:997 arg1 1-4GlcNAc-PA 1019:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 0 85 theme 1-antitrypsin 55:67 arg1 chains 33:38 the sugar chains 23:38 the sugar chains of human alpha 1-antitrypsin 23:67 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 1 86 theme stepwise 416:423 arg1 digestion 440:448 stepwise exoglycosidase digestion 416:448 stepwise exoglycosidase digestion 416:448 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 87 theme Chemical 142:149 arg1 structures 151:160 Chemical structures 142:160 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) 142:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 2 88 theme alpha 757:761 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 88 theme alpha 757:761 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 88 theme alpha 757:761 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 89 theme Lens 320:323 arg1 LCA 347:349 LCA 347:349 LCA 347:349 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 89 theme Lens 320:323 arg1 agglutinin 335:344 Lens culinaris agglutinin 320:344 Lens culinaris agglutinin (LCA) 320:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 0 90 from analysis 11:18 arg1 chains 33:38 the sugar chains 23:38 the sugar chains of human alpha 1-antitrypsin 23:67 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 2 91 from residue 717:723 arg1 residue 672:678 a fucose residue 663:678 a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, 663:859 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 4 92 theme chains 1344:1349 arg1 increment 1387:1395 an increment 1384:1395 an increment in fucosylation 1384:1411 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 4 92 theme chains 1344:1349 arg1 feature 1316:1322 a characteristic feature 1299:1322 a characteristic feature of the carbohydrate chains of AAT from patients with HCC 1299:1379 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 0 93 theme fucosylated 82:92 arg1 glycan 106:111 fucosylated biantennary glycan 82:111 fucosylated biantennary glycan 82:111 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 1 94 dep reversed-phase 470:483 arg1 chromatography 532:545 high-performance liquid chromatography 508:545 high-performance liquid chromatography 508:545 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 2 95 theme 1-4GlcNAc 963:971 arg1 alpha 985:989 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 95 theme 1-4GlcNAc 963:971 arg1 alpha 944:948 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6 913:952 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 4 96 theme AAT 1354:1356 arg1 chains 1344:1349 the carbohydrate chains 1327:1349 the carbohydrate chains of AAT from patients with HCC 1327:1379 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 0 97 theme glycan 106:111 arg1 presence 70:77 presence 70:77 presence of fucosylated biantennary glycan in hepatocellular carcinoma 70:139 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 1 98 from structures 151:160 arg1 individuals 278:288 healthy individuals 270:288 healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) 270:350 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 98 from structures 151:160 arg1 patients 216:223 patients 216:223 patients with hepatocellular carcinoma (HCC) 216:259 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 2 99 theme Gal 954:956 arg1 alpha 985:989 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 954:993 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 99 theme Gal 954:956 arg1 alpha 944:948 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6 913:952 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 100 theme 1:0.6 1053:1057 arg1 ratio 1038:1042 a ratio 1036:1042 a ratio of about 1:0.6 1036:1057 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 0 101 dep presence 70:77 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis on the sugar chains of human alpha 1-antitrypsin 0:67 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 2 102 theme N-acetylglucosamine 697:715 arg1 GlcNAc-PA 850:858 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 102 theme N-acetylglucosamine 697:715 arg1 residue 717:723 the innermost N-acetylglucosamine residue 683:723 the innermost N-acetylglucosamine residue 683:723 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 103 with chain 881:885 arg1 residue 672:678 a fucose residue 663:678 a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, 663:859 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 4 104 from increment 1387:1395 arg1 fucosylation 1400:1411 fucosylation 1400:1411 fucosylation 1400:1411 These results indicate that a characteristic feature of the carbohydrate chains of AAT from patients with HCC is an increment in fucosylation. 8390218 2 105 theme 1-4GlcNAc 922:930 arg1 beta 932:935 Gal beta 1-4GlcNAc beta 913:935 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 106 theme high-performance 508:523 arg1 chromatography 532:545 high-performance liquid chromatography 508:545 high-performance liquid chromatography 508:545 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 0 107 theme human 43:47 arg1 1-antitrypsin 55:67 human alpha 1-antitrypsin 43:67 human alpha 1-antitrypsin 43:67 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 3 108 theme AAT 1091:1093 arg1 species 1080:1086 The LCA-nonreactive species 1060:1086 The LCA-nonreactive species of AAT 1060:1093 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 109 theme Gal 913:915 arg1 beta 932:935 Gal beta 1-4GlcNAc beta 913:935 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 110 theme beta 1014:1017 arg1 residue 904:910 a fucose residue 895:910 a fucose residue 895:910 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 110 theme beta 1014:1017 arg1 1-4GlcNAc-PA 1019:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA 913:1030 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 0 111 attach presence 70:77 arg2 glycan 106:111 fucosylated biantennary glycan 82:111 fucosylated biantennary glycan 82:111 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 0 111 attach presence 70:77 arg1 carcinoma 131:139 hepatocellular carcinoma 116:139 hepatocellular carcinoma 116:139 Structural analysis on the sugar chains of human alpha 1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. 8390218 2 112 theme 1-4GlcNAc 817:825 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 112 theme 1-4GlcNAc 817:825 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 112 theme 1-4GlcNAc 817:825 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 3 113 theme sugar 1121:1125 arg1 alpha 1205:1209 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 1174:1213 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 3 113 theme sugar 1121:1125 arg1 beta 1234:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1105:1237 the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc 1105:1247 The LCA-nonreactive species of AAT contained the biantennary sugar chain Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc as a major component. 8390218 2 114 theme Man 808:810 arg1 alpha 798:802 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3 767:806 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 114 theme Man 808:810 arg1 beta 827:830 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4 726:834 Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA 726:858 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 114 theme Man 808:810 arg1 alpha 840:844 Fuc alpha 1-6 836:848 Fuc alpha 1-6 836:848 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 2 115 with patients 599:606 arg1 HCC 613:615 HCC 613:615 HCC 613:615 We found that the LCA-reactive species of AAT from patients with HCC carried both the biantennary sugar chain with a fucose residue at the innermost N-acetylglucosamine residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc-PA, and the biantennary chain without a fucose residue, Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc-PA, at a ratio of about 1:0.6. 8390218 1 116 theme hepatocellular 230:243 arg1 HCC 256:258 HCC 256:258 HCC 256:258 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 8390218 1 116 theme hepatocellular 230:243 arg1 carcinoma 245:253 hepatocellular carcinoma 230:253 hepatocellular carcinoma (HCC) 230:259 Chemical structures of the sugar chains of alpha 1-antitrypsin (AAT) from patients with hepatocellular carcinoma (HCC) and from healthy individuals with a different affinity for Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion in combination with reversed-phase and size-fractionation high-performance liquid chromatography. 2121479 8 0 from GlcNAc 1482:1487 arg1 residue 1450:1456 an alpha 1-6-linked Fuc residue 1426:1456 an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc 1426:1487 Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. 2121479 2 1 theme asparagine 402:411 arg1 F 421:421 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 363:421 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 363:421 The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 2121479 4 2 theme chains 660:665 arg1 structures 629:638 The structures 625:638 The structures of the carbohydrate chains 625:665 The structures of the carbohydrate chains were determined by 500- or 600-MHz 1H-NMR spectroscopy. 2121479 2 3 theme glycoprotein 311:322 arg1 hormone 324:330 the recombinant glycoprotein hormone 295:330 the recombinant glycoprotein hormone 295:330 The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 2121479 5 4 gly trisialylated 866:878 arg1 tri-antennary 880:892 trisialylated tri-antennary 866:892 trisialylated tri-antennary (13%) 866:898 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 4 gly trisialylated 866:878 arg1 % 897:897 13% 895:897 13% 895:897 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 6 5 theme tetra-antennary 1168:1182 arg1 oligosaccharides 1184:1199 tetra-antennary oligosaccharides 1168:1199 tetra-antennary oligosaccharides containing alpha 2-3- 1168:1221 Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing alpha 2-3- as well as alpha 2-6-linked Neu5Ac residues were reported. 2121479 1 6 theme human 199:203 arg1 follitropin 205:215 Biologically active recombinant human follitropin 167:215 Biologically active recombinant human follitropin 167:215 Biologically active recombinant human follitropin has been expressed in Chinese hamster ovary cells. 2121479 5 7 gly trisialylated 901:913 arg1 tri'-antennary 915:928 trisialylated tri'-antennary 901:928 trisialylated tri'-antennary (8%) 901:933 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 7 gly trisialylated 901:913 arg1 % 932:932 8% 931:932 8% 931:932 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 4 8 theme 600-MHz 694:700 arg1 spectroscopy 709:720 500- or 600-MHz 1H-NMR spectroscopy 686:720 500- or 600-MHz 1H-NMR spectroscopy 686:720 The structures of the carbohydrate chains were determined by 500- or 600-MHz 1H-NMR spectroscopy. 2121479 3 9 theme FPLC 582:585 arg1 combination 567:577 a combination 565:577 a combination of FPLC 565:585 The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH2. 2121479 5 10 theme trisialylated 866:878 arg1 tri-antennary 880:892 trisialylated tri-antennary 866:892 trisialylated tri-antennary (13%) 866:898 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 10 theme trisialylated 866:878 arg1 % 897:897 13% 895:897 13% 895:897 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 9 11 theme additional 1697:1706 arg1 units 1728:1732 one or more additional N-acetyllactosamine units 1685:1732 one or more additional N-acetyllactosamine units 1685:1732 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 6 12 theme Neu5Ac 1251:1256 arg1 residues 1258:1265 2-6-linked Neu5Ac residues 1240:1265 2-6-linked Neu5Ac residues 1240:1265 Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing alpha 2-3- as well as alpha 2-6-linked Neu5Ac residues were reported. 2121479 0 13 theme hamster 146:152 arg1 cells 160:164 Chinese hamster ovary cells 138:164 Chinese hamster ovary cells 138:164 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 1 14 theme Chinese 239:245 arg1 cells 261:265 Chinese hamster ovary cells 239:265 Chinese hamster ovary cells 239:265 Biologically active recombinant human follitropin has been expressed in Chinese hamster ovary cells. 2121479 5 15 theme carbohydrates 746:758 arg1 types 737:741 The following types 723:741 The following types of carbohydrates 723:758 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 16 theme 2-3-linked 1056:1065 arg1 acid 1086:1089 alpha 2-3-linked N-acetylneuraminic acid 1050:1089 alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac) 1050:1098 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 16 theme 2-3-linked 1056:1065 arg1 Neu5Ac 1092:1097 Neu5Ac 1092:1097 Neu5Ac 1092:1097 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 17 theme N-acetylneuraminic 1067:1084 arg1 acid 1086:1089 alpha 2-3-linked N-acetylneuraminic acid 1050:1089 alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac) 1050:1098 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 17 theme N-acetylneuraminic 1067:1084 arg1 Neu5Ac 1092:1097 Neu5Ac 1092:1097 Neu5Ac 1092:1097 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 18 link 2-3-linked 1056:1065 arg1 acid 1086:1089 alpha 2-3-linked N-acetylneuraminic acid 1050:1089 alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac) 1050:1098 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 18 link 2-3-linked 1056:1065 arg1 Neu5Ac 1092:1097 Neu5Ac 1092:1097 Neu5Ac 1092:1097 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 0 19 theme N-linked 63:70 arg1 chains 85:90 the intact sialylated N-linked carbohydrate chains 41:90 the intact sialylated N-linked carbohydrate chains of recombinant human follitropin 41:123 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 0 20 theme chains 85:90 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 0 20 theme chains 85:90 arg1 determination 24:36 structure determination 14:36 structure determination 14:36 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 3 21 gly N-deglycosylated 469:484 arg1 protein 486:492 the N-deglycosylated protein 465:492 the N-deglycosylated protein 465:492 The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH2. 2121479 1 22 theme active 180:185 arg1 follitropin 205:215 Biologically active recombinant human follitropin 167:215 Biologically active recombinant human follitropin 167:215 Biologically active recombinant human follitropin has been expressed in Chinese hamster ovary cells. 2121479 0 23 theme recombinant 95:105 arg1 follitropin 113:123 recombinant human follitropin 95:123 recombinant human follitropin 95:123 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 8 24 link 1-6-linked 1435:1444 arg1 residue 1450:1456 an alpha 1-6-linked Fuc residue 1426:1456 an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc 1426:1487 Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. 2121479 8 25 theme pituitary 1526:1534 arg1 follitropin 1536:1546 pituitary follitropin 1526:1546 pituitary follitropin 1526:1546 Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. 2121479 5 26 theme disialylated 801:812 arg1 diantennary 814:824 disialylated diantennary 801:824 disialylated diantennary (43%) 801:830 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 26 theme disialylated 801:812 arg1 % 829:829 43% 827:829 43% 827:829 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 8 27 from % 1521:1521 arg1 follitropin 1536:1546 pituitary follitropin 1526:1546 pituitary follitropin 1526:1546 Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. 2121479 9 28 theme tri'- 1570:1574 arg1 % 1648:1648 less than 5% 1637:1648 less than 5% 1637:1648 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 28 theme tri'- 1570:1574 arg1 amounts 1628:1634 tri'- and tetra-antennary oligosaccharide fractions small amounts 1570:1634 tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds 1570:1662 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 28 theme tri'- 1570:1574 arg1 compounds 1654:1662 compounds 1654:1662 compounds 1654:1662 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 5 29 gly disialylated 801:812 arg1 diantennary 814:824 disialylated diantennary 801:824 disialylated diantennary (43%) 801:830 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 29 gly disialylated 801:812 arg1 % 829:829 43% 827:829 43% 827:829 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 0 30 theme structure 14:22 arg1 determination 24:36 structure determination 14:36 structure determination 14:36 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 9 31 theme tetra-antennary 1580:1594 arg1 fractions 1612:1620 tetra-antennary oligosaccharide fractions 1580:1620 tetra-antennary oligosaccharide fractions 1580:1620 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 3 32 theme N-deglycosylated 469:484 arg1 protein 486:492 the N-deglycosylated protein 465:492 the N-deglycosylated protein 465:492 The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH2. 2121479 3 33 theme Bio-Gel 530:536 arg1 P-100 538:542 Bio-Gel P-100 530:542 Bio-Gel P-100 530:542 The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH2. 2121479 9 34 theme fractions 1612:1620 arg1 % 1648:1648 less than 5% 1637:1648 less than 5% 1637:1648 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 34 theme fractions 1612:1620 arg1 amounts 1628:1634 tri'- and tetra-antennary oligosaccharide fractions small amounts 1570:1634 tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds 1570:1662 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 34 theme fractions 1612:1620 arg1 compounds 1654:1662 compounds 1654:1662 compounds 1654:1662 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 7 35 from present 1312:1318 arg1 follitropin 1330:1340 native follitropin 1323:1340 native follitropin 1323:1340 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 7 36 attach present 1312:1318 arg2 residues 1303:1310 The bisecting GlcNAc residues 1282:1310 The bisecting GlcNAc residues present in native follitropin 1282:1340 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 7 36 attach present 1312:1318 arg1 follitropin 1330:1340 native follitropin 1323:1340 native follitropin 1323:1340 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 8 37 theme alpha 1429:1433 arg1 residue 1450:1456 an alpha 1-6-linked Fuc residue 1426:1456 an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc 1426:1487 Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. 2121479 0 38 theme intact 45:50 arg1 chains 85:90 the intact sialylated N-linked carbohydrate chains 41:90 the intact sialylated N-linked carbohydrate chains of recombinant human follitropin 41:123 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 5 39 theme alpha 1050:1054 arg1 acid 1086:1089 alpha 2-3-linked N-acetylneuraminic acid 1050:1089 alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac) 1050:1098 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 39 theme alpha 1050:1054 arg1 Neu5Ac 1092:1097 Neu5Ac 1092:1097 Neu5Ac 1092:1097 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 6 40 theme alpha 1212:1216 arg1 2-3- 1218:1221 alpha 2-3- 1212:1221 alpha 2-3- 1212:1221 Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing alpha 2-3- as well as alpha 2-6-linked Neu5Ac residues were reported. 2121479 8 41 theme Fuc 1446:1448 arg1 residue 1450:1456 an alpha 1-6-linked Fuc residue 1426:1456 an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc 1426:1487 Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. 2121479 1 42 theme hamster 247:253 arg1 cells 261:265 Chinese hamster ovary cells 239:265 Chinese hamster ovary cells 239:265 Biologically active recombinant human follitropin has been expressed in Chinese hamster ovary cells. 2121479 5 43 theme carbohydrate 1005:1016 arg1 chains 1018:1023 carbohydrate chains 1005:1023 carbohydrate chains 1005:1023 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 43 theme carbohydrate 1005:1016 arg1 all 1026:1028 all 1026:1028 all 1026:1028 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 7 44 theme bisecting 1286:1294 arg1 residues 1303:1310 The bisecting GlcNAc residues 1282:1310 The bisecting GlcNAc residues present in native follitropin 1282:1340 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 5 45 theme disialylated 833:844 arg1 tri-antennary 846:858 disialylated tri-antennary 833:858 disialylated tri-antennary (5%) 833:863 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 45 theme disialylated 833:844 arg1 % 862:862 5% 861:862 5% 861:862 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 0 46 gly sialylated 52:61 arg1 chains 85:90 the intact sialylated N-linked carbohydrate chains 41:90 the intact sialylated N-linked carbohydrate chains of recombinant human follitropin 41:123 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 6 47 theme pituitary 1117:1125 arg1 mono- 1139:1143 pituitary follitropin mono- 1117:1143 pituitary follitropin mono- 1117:1143 Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing alpha 2-3- as well as alpha 2-6-linked Neu5Ac residues were reported. 2121479 6 48 contain containing 1201:1210 arg1 oligosaccharides 1184:1199 tetra-antennary oligosaccharides 1168:1199 tetra-antennary oligosaccharides containing alpha 2-3- 1168:1221 Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing alpha 2-3- as well as alpha 2-6-linked Neu5Ac residues were reported. 2121479 6 48 contain containing 1201:1210 arg2 2-3- 1218:1221 alpha 2-3- 1212:1221 alpha 2-3- 1212:1221 Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing alpha 2-3- as well as alpha 2-6-linked Neu5Ac residues were reported. 2121479 2 49 theme amidase 413:419 arg1 F 421:421 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 363:421 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 363:421 The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 2121479 2 50 gly glycoprotein 311:322 arg1 glycoprotein 311:322 the recombinant glycoprotein hormone 295:330 the recombinant glycoprotein hormone 295:330 The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 2121479 5 51 theme following 727:735 arg1 types 737:741 The following types 723:741 The following types of carbohydrates 723:758 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 2 52 theme hormone 324:330 arg1 chains 285:290 The carbohydrate chains 268:290 The carbohydrate chains of the recombinant glycoprotein hormone 268:330 The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 2121479 9 53 theme compounds 1654:1662 arg1 % 1648:1648 less than 5% 1637:1648 less than 5% 1637:1648 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 53 theme compounds 1654:1662 arg1 amounts 1628:1634 tri'- and tetra-antennary oligosaccharide fractions small amounts 1570:1634 tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds 1570:1662 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 53 theme compounds 1654:1662 arg1 compounds 1654:1662 compounds 1654:1662 compounds 1654:1662 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 4 54 theme carbohydrate 647:658 arg1 chains 660:665 the carbohydrate chains 643:665 the carbohydrate chains 643:665 The structures of the carbohydrate chains were determined by 500- or 600-MHz 1H-NMR spectroscopy. 2121479 2 55 theme recombinant 299:309 arg1 hormone 324:330 the recombinant glycoprotein hormone 295:330 the recombinant glycoprotein hormone 295:330 The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 2121479 1 56 theme recombinant 187:197 arg1 follitropin 205:215 Biologically active recombinant human follitropin 167:215 Biologically active recombinant human follitropin 167:215 Biologically active recombinant human follitropin has been expressed in Chinese hamster ovary cells. 2121479 7 57 gly glycoprotein 1379:1390 arg1 glycoprotein 1379:1390 the recombinant glycoprotein 1363:1390 the recombinant glycoprotein 1363:1390 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 5 58 theme monosialylated 767:780 arg1 diantennary 782:792 monosialylated diantennary 767:792 monosialylated diantennary (10%) 767:798 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 58 theme monosialylated 767:780 arg1 % 797:797 10% 795:797 10% 795:797 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 9 59 located detected 1669:1676 arg2 compounds 1654:1662 compounds 1654:1662 compounds 1654:1662 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 59 located detected 1669:1676 arg1 some 1552:1555 some 1552:1555 some 1552:1555 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 59 located detected 1669:1676 arg1 tri- 1564:1567 the tri- 1560:1567 the tri- 1560:1567 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 59 located detected 1669:1676 arg2 amounts 1628:1634 tri'- and tetra-antennary oligosaccharide fractions small amounts 1570:1634 tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds 1570:1662 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 59 located detected 1669:1676 arg2 % 1648:1648 less than 5% 1637:1648 less than 5% 1637:1648 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 8 60 theme asparagine-bound 1465:1480 arg1 GlcNAc 1482:1487 the asparagine-bound GlcNAc 1461:1487 the asparagine-bound GlcNAc 1461:1487 Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. 2121479 6 61 link 2-6-linked 1240:1249 arg1 residues 1258:1265 2-6-linked Neu5Ac residues 1240:1265 2-6-linked Neu5Ac residues 1240:1265 Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing alpha 2-3- as well as alpha 2-6-linked Neu5Ac residues were reported. 2121479 0 62 theme ovary 154:158 arg1 cells 160:164 Chinese hamster ovary cells 138:164 Chinese hamster ovary cells 138:164 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 9 63 theme N-acetyllactosamine 1708:1726 arg1 units 1728:1732 one or more additional N-acetyllactosamine units 1685:1732 one or more additional N-acetyllactosamine units 1685:1732 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 6 64 theme 2-6-linked 1240:1249 arg1 residues 1258:1265 2-6-linked Neu5Ac residues 1240:1265 2-6-linked Neu5Ac residues 1240:1265 Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing alpha 2-3- as well as alpha 2-6-linked Neu5Ac residues were reported. 2121479 4 65 theme 1H-NMR 702:707 arg1 spectroscopy 709:720 500- or 600-MHz 1H-NMR spectroscopy 686:720 500- or 600-MHz 1H-NMR spectroscopy 686:720 The structures of the carbohydrate chains were determined by 500- or 600-MHz 1H-NMR spectroscopy. 2121479 0 66 theme Chinese 138:144 arg1 cells 160:164 Chinese hamster ovary cells 138:164 Chinese hamster ovary cells 138:164 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 5 67 gly monosialylated 767:780 arg1 diantennary 782:792 monosialylated diantennary 767:792 monosialylated diantennary (10%) 767:798 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 67 gly monosialylated 767:780 arg1 % 797:797 10% 795:797 10% 795:797 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 7 68 located detected 1351:1358 arg1 glycoprotein 1379:1390 the recombinant glycoprotein 1363:1390 the recombinant glycoprotein 1363:1390 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 7 68 located detected 1351:1358 arg2 residues 1303:1310 The bisecting GlcNAc residues 1282:1310 The bisecting GlcNAc residues present in native follitropin 1282:1340 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 7 69 from follitropin 1330:1340 arg1 present 1312:1318 present 1312:1318 present 1312:1318 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 0 70 theme carbohydrate 72:83 arg1 chains 85:90 the intact sialylated N-linked carbohydrate chains 41:90 the intact sialylated N-linked carbohydrate chains of recombinant human follitropin 41:123 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 2 71 theme carbohydrate 272:283 arg1 chains 285:290 The carbohydrate chains 268:290 The carbohydrate chains of the recombinant glycoprotein hormone 268:330 The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 2121479 5 72 theme trisialylated 901:913 arg1 tri'-antennary 915:928 trisialylated tri'-antennary 901:928 trisialylated tri'-antennary (8%) 901:933 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 72 theme trisialylated 901:913 arg1 % 932:932 8% 931:932 8% 931:932 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 7 73 theme recombinant 1367:1377 arg1 glycoprotein 1379:1390 the recombinant glycoprotein 1363:1390 the recombinant glycoprotein 1363:1390 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 3 74 from Q 595:595 arg1 Lichrosorb-NH2 609:622 Lichrosorb-NH2 609:622 Lichrosorb-NH2 609:622 The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH2. 2121479 5 75 dep diantennary 782:792 arg1 type 997:1000 N-acetyllactosamine type 977:1000 N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac) 977:1098 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 3 76 from HPLC 601:604 arg1 Lichrosorb-NH2 609:622 Lichrosorb-NH2 609:622 Lichrosorb-NH2 609:622 The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH2. 2121479 0 77 theme human 107:111 arg1 follitropin 113:123 recombinant human follitropin 95:123 recombinant human follitropin 95:123 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 5 78 gly tetrasialylated 940:954 arg1 tetraantennary 956:969 tetrasialylated tetraantennary 940:969 tetrasialylated tetraantennary (12%) 940:975 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 78 gly tetrasialylated 940:954 arg1 % 974:974 12% 972:974 12% 972:974 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 79 theme N-acetyllactosamine 977:995 arg1 type 997:1000 N-acetyllactosamine type 977:1000 N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac) 977:1098 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 80 theme tetrasialylated 940:954 arg1 tetraantennary 956:969 tetrasialylated tetraantennary 940:969 tetrasialylated tetraantennary (12%) 940:975 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 80 theme tetrasialylated 940:954 arg1 % 974:974 12% 972:974 12% 972:974 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 3 81 theme gel-permeation 497:510 arg1 chromatography 512:525 gel-permeation chromatography 497:525 gel-permeation chromatography on Bio-Gel P-100 497:542 The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH2. 2121479 7 82 theme native 1323:1328 arg1 follitropin 1330:1340 native follitropin 1323:1340 native follitropin 1323:1340 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 9 83 theme oligosaccharide 1596:1610 arg1 fractions 1612:1620 tetra-antennary oligosaccharide fractions 1580:1620 tetra-antennary oligosaccharide fractions 1580:1620 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 7 84 theme present 1312:1318 arg1 residues 1303:1310 The bisecting GlcNAc residues 1282:1310 The bisecting GlcNAc residues present in native follitropin 1282:1340 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 0 85 theme follitropin 113:123 arg1 chains 85:90 the intact sialylated N-linked carbohydrate chains 41:90 the intact sialylated N-linked carbohydrate chains of recombinant human follitropin 41:123 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 0 86 theme sialylated 52:61 arg1 chains 85:90 the intact sialylated N-linked carbohydrate chains 41:90 the intact sialylated N-linked carbohydrate chains of recombinant human follitropin 41:123 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 9 87 theme small 1622:1626 arg1 % 1648:1648 less than 5% 1637:1648 less than 5% 1637:1648 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 87 theme small 1622:1626 arg1 amounts 1628:1634 tri'- and tetra-antennary oligosaccharide fractions small amounts 1570:1634 tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds 1570:1662 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 9 87 theme small 1622:1626 arg1 compounds 1654:1662 compounds 1654:1662 compounds 1654:1662 In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units. 2121479 7 88 theme GlcNAc 1296:1301 arg1 residues 1303:1310 The bisecting GlcNAc residues 1282:1310 The bisecting GlcNAc residues present in native follitropin 1282:1340 The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. 2121479 8 89 contain have 1421:1424 arg1 % 1419:1419 29% 1417:1419 29% 1417:1419 Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. 2121479 8 89 contain have 1421:1424 arg2 residue 1450:1456 an alpha 1-6-linked Fuc residue 1426:1456 an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc 1426:1487 Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. 2121479 2 90 theme N-acetyl-beta-glucosaminyl 375:400 arg1 F 421:421 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 363:421 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 363:421 The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 2121479 0 91 link N-linked 63:70 arg1 chains 85:90 the intact sialylated N-linked carbohydrate chains 41:90 the intact sialylated N-linked carbohydrate chains of recombinant human follitropin 41:123 Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells. 2121479 8 92 theme 1-6-linked 1435:1444 arg1 residue 1450:1456 an alpha 1-6-linked Fuc residue 1426:1456 an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc 1426:1487 Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. 2121479 2 93 theme peptide-N4- 363:373 arg1 F 421:421 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 363:421 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F 363:421 The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. 2121479 1 94 theme ovary 255:259 arg1 cells 261:265 Chinese hamster ovary cells 239:265 Chinese hamster ovary cells 239:265 Biologically active recombinant human follitropin has been expressed in Chinese hamster ovary cells. 2121479 5 95 theme chains 1018:1023 arg1 type 997:1000 N-acetyllactosamine type 977:1000 N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac) 977:1098 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 6 96 theme follitropin 1127:1137 arg1 mono- 1139:1143 pituitary follitropin mono- 1117:1143 pituitary follitropin mono- 1117:1143 Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing alpha 2-3- as well as alpha 2-6-linked Neu5Ac residues were reported. 2121479 4 97 theme 500- 686:689 arg1 spectroscopy 709:720 500- or 600-MHz 1H-NMR spectroscopy 686:720 500- or 600-MHz 1H-NMR spectroscopy 686:720 The structures of the carbohydrate chains were determined by 500- or 600-MHz 1H-NMR spectroscopy. 2121479 5 98 gly disialylated 833:844 arg1 tri-antennary 846:858 disialylated tri-antennary 833:858 disialylated tri-antennary (5%) 833:863 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 5 98 gly disialylated 833:844 arg1 % 862:862 5% 861:862 5% 861:862 The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). 2121479 3 99 from chromatography 512:525 arg1 P-100 538:542 Bio-Gel P-100 530:542 Bio-Gel P-100 530:542 The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH2. 2121479 3 100 theme Mono 590:593 arg1 Q 595:595 Mono Q 590:595 Mono Q 590:595 The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH2. 8011069 5 0 theme primary 752:758 arg1 structure 760:768 the primary structure 748:768 the primary structure of the major N-linked oligosaccharide component 748:816 By 600-MHz 1H-NMR spectroscopy, the primary structure of the major N-linked oligosaccharide component was established to be: [formula: see text] 8011069 1 1 theme structural 144:153 arg1 properties 155:164 structural properties 144:164 structural properties 144:164 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 0 2 from structure 8:16 arg1 transferrin 57:67 human seminal transferrin 43:67 human seminal transferrin 43:67 Primary structure of the major glycan from human seminal transferrin. 8011069 5 3 dep established 822:832 arg1 [formula 841:848 [formula 841:848 [formula: see text] 841:859 By 600-MHz 1H-NMR spectroscopy, the primary structure of the major N-linked oligosaccharide component was established to be: [formula: see text] 8011069 4 4 theme ethanol 564:570 arg1 precipitation 572:584 ethanol precipitation 564:584 ethanol precipitation 564:584 After ethanol precipitation and fractionation on Bio-Gel P-6 and Bio-Gel P-2, the oligosaccharide was further purified on Mono-Q and desalted on Bio-Gel P-2. 8011069 4 5 from fractionation 590:602 arg1 P-6 615:617 Bio-Gel P-6 607:617 Bio-Gel P-6 607:617 After ethanol precipitation and fractionation on Bio-Gel P-6 and Bio-Gel P-2, the oligosaccharide was further purified on Mono-Q and desalted on Bio-Gel P-2. 8011069 4 5 from fractionation 590:602 arg1 P-2 631:633 Bio-Gel P-2 623:633 Bio-Gel P-2 623:633 After ethanol precipitation and fractionation on Bio-Gel P-6 and Bio-Gel P-2, the oligosaccharide was further purified on Mono-Q and desalted on Bio-Gel P-2. 8011069 2 6 theme monosaccharide 279:292 arg1 analysis 294:301 monosaccharide analysis 279:301 monosaccharide analysis 279:301 The carbohydrate content of the purified glycoprotein amount to 6.1%, and monosaccharide analysis revealed the major oligosaccharide moiety to be of the N-glycoside type. 8011069 2 7 theme major 316:320 arg1 moiety 338:343 the major oligosaccharide moiety 312:343 the major oligosaccharide moiety to be of the N-glycoside type 312:373 The carbohydrate content of the purified glycoprotein amount to 6.1%, and monosaccharide analysis revealed the major oligosaccharide moiety to be of the N-glycoside type. 8011069 2 8 theme oligosaccharide 322:336 arg1 moiety 338:343 the major oligosaccharide moiety 312:343 the major oligosaccharide moiety to be of the N-glycoside type 312:373 The carbohydrate content of the purified glycoprotein amount to 6.1%, and monosaccharide analysis revealed the major oligosaccharide moiety to be of the N-glycoside type. 8011069 4 9 from precipitation 572:584 arg1 P-6 615:617 Bio-Gel P-6 607:617 Bio-Gel P-6 607:617 After ethanol precipitation and fractionation on Bio-Gel P-6 and Bio-Gel P-2, the oligosaccharide was further purified on Mono-Q and desalted on Bio-Gel P-2. 8011069 4 9 from precipitation 572:584 arg1 P-2 631:633 Bio-Gel P-2 623:633 Bio-Gel P-2 623:633 After ethanol precipitation and fractionation on Bio-Gel P-6 and Bio-Gel P-2, the oligosaccharide was further purified on Mono-Q and desalted on Bio-Gel P-2. 8011069 5 10 theme oligosaccharide 792:806 arg1 component 808:816 the major N-linked oligosaccharide component 773:816 the major N-linked oligosaccharide component 773:816 By 600-MHz 1H-NMR spectroscopy, the primary structure of the major N-linked oligosaccharide component was established to be: [formula: see text] 8011069 3 11 theme detergents 510:519 arg1 presence 498:505 the presence 494:505 the presence of detergents such as SDS and beta-octylglucoside 494:555 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 1 12 theme Human 70:74 arg1 transferrin 84:94 Human seminal transferrin 70:94 Human seminal transferrin (HSmT) 70:101 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 1 12 theme Human 70:74 arg1 glycoprotein 125:136 an iron-containing glycoprotein 106:136 an iron-containing glycoprotein whose structural properties have not been adequately investigated 106:202 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 1 12 theme Human 70:74 arg1 HSmT 97:100 HSmT 97:100 HSmT 97:100 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 5 13 theme 1H-NMR 727:732 arg1 spectroscopy 734:745 600-MHz 1H-NMR spectroscopy 719:745 600-MHz 1H-NMR spectroscopy 719:745 By 600-MHz 1H-NMR spectroscopy, the primary structure of the major N-linked oligosaccharide component was established to be: [formula: see text] 8011069 3 14 theme carbohydrate 380:391 arg1 chains 393:398 The carbohydrate chains 376:398 The carbohydrate chains 376:398 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 1 15 theme seminal 76:82 arg1 transferrin 84:94 Human seminal transferrin 70:94 Human seminal transferrin (HSmT) 70:101 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 1 15 theme seminal 76:82 arg1 glycoprotein 125:136 an iron-containing glycoprotein 106:136 an iron-containing glycoprotein whose structural properties have not been adequately investigated 106:202 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 1 15 theme seminal 76:82 arg1 HSmT 97:100 HSmT 97:100 HSmT 97:100 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 3 16 theme iron-free 423:431 arg1 form 433:436 the iron-free form 419:436 the iron-free form 419:436 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 0 17 theme Primary 0:6 arg1 structure 8:16 Primary structure 0:16 Primary structure of the major glycan from human seminal transferrin 0:67 Primary structure of the major glycan from human seminal transferrin. 8011069 2 18 gly glycoprotein 246:257 arg1 glycoprotein 246:257 the purified glycoprotein 233:257 the purified glycoprotein 233:257 The carbohydrate content of the purified glycoprotein amount to 6.1%, and monosaccharide analysis revealed the major oligosaccharide moiety to be of the N-glycoside type. 8011069 5 19 theme component 808:816 arg1 structure 760:768 the primary structure 748:768 the primary structure of the major N-linked oligosaccharide component 748:816 By 600-MHz 1H-NMR spectroscopy, the primary structure of the major N-linked oligosaccharide component was established to be: [formula: see text] 8011069 5 20 theme major 777:781 arg1 component 808:816 the major N-linked oligosaccharide component 773:816 the major N-linked oligosaccharide component 773:816 By 600-MHz 1H-NMR spectroscopy, the primary structure of the major N-linked oligosaccharide component was established to be: [formula: see text] 8011069 3 21 theme N-glycosidase 464:476 arg1 F 488:488 PNGase F 481:488 PNGase F 481:488 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 3 21 theme N-glycosidase 464:476 arg1 F 478:478 peptide N-glycosidase F 456:478 peptide N-glycosidase F (PNGase F) 456:489 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 4 22 theme Bio-Gel 623:629 arg1 P-2 631:633 Bio-Gel P-2 623:633 Bio-Gel P-2 623:633 After ethanol precipitation and fractionation on Bio-Gel P-6 and Bio-Gel P-2, the oligosaccharide was further purified on Mono-Q and desalted on Bio-Gel P-2. 8011069 0 23 theme glycan 31:36 arg1 structure 8:16 Primary structure 0:16 Primary structure of the major glycan from human seminal transferrin 0:67 Primary structure of the major glycan from human seminal transferrin. 8011069 2 24 theme purified 237:244 arg1 glycoprotein 246:257 the purified glycoprotein 233:257 the purified glycoprotein 233:257 The carbohydrate content of the purified glycoprotein amount to 6.1%, and monosaccharide analysis revealed the major oligosaccharide moiety to be of the N-glycoside type. 8011069 0 25 theme major 25:29 arg1 glycan 31:36 the major glycan 21:36 the major glycan from human seminal transferrin 21:67 Primary structure of the major glycan from human seminal transferrin. 8011069 3 26 attach released 405:412 arg2 chains 393:398 The carbohydrate chains 376:398 The carbohydrate chains 376:398 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 3 26 attach released 405:412 arg1 form 433:436 the iron-free form 419:436 the iron-free form 419:436 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 5 27 link N-linked 783:790 arg1 component 808:816 the major N-linked oligosaccharide component 773:816 the major N-linked oligosaccharide component 773:816 By 600-MHz 1H-NMR spectroscopy, the primary structure of the major N-linked oligosaccharide component was established to be: [formula: see text] 8011069 3 28 theme peptide 456:462 arg1 F 488:488 PNGase F 481:488 PNGase F 481:488 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 3 28 theme peptide 456:462 arg1 F 478:478 peptide N-glycosidase F 456:478 peptide N-glycosidase F (PNGase F) 456:489 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 0 29 theme human 43:47 arg1 transferrin 57:67 human seminal transferrin 43:67 human seminal transferrin 43:67 Primary structure of the major glycan from human seminal transferrin. 8011069 4 30 theme Bio-Gel 703:709 arg1 P-2 711:713 Bio-Gel P-2 703:713 Bio-Gel P-2 703:713 After ethanol precipitation and fractionation on Bio-Gel P-6 and Bio-Gel P-2, the oligosaccharide was further purified on Mono-Q and desalted on Bio-Gel P-2. 8011069 5 31 theme N-linked 783:790 arg1 component 808:816 the major N-linked oligosaccharide component 773:816 the major N-linked oligosaccharide component 773:816 By 600-MHz 1H-NMR spectroscopy, the primary structure of the major N-linked oligosaccharide component was established to be: [formula: see text] 8011069 1 32 gly glycoprotein 125:136 arg1 transferrin 84:94 Human seminal transferrin 70:94 Human seminal transferrin (HSmT) 70:101 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 1 32 gly glycoprotein 125:136 arg1 glycoprotein 125:136 an iron-containing glycoprotein 106:136 an iron-containing glycoprotein whose structural properties have not been adequately investigated 106:202 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 2 33 theme carbohydrate 209:220 arg1 content 222:228 The carbohydrate content 205:228 The carbohydrate content of the purified glycoprotein 205:257 The carbohydrate content of the purified glycoprotein amount to 6.1%, and monosaccharide analysis revealed the major oligosaccharide moiety to be of the N-glycoside type. 8011069 0 34 from transferrin 57:67 arg1 glycan 31:36 the major glycan 21:36 the major glycan from human seminal transferrin 21:67 Primary structure of the major glycan from human seminal transferrin. 8011069 0 34 from transferrin 57:67 arg1 structure 8:16 Primary structure 0:16 Primary structure of the major glycan from human seminal transferrin 0:67 Primary structure of the major glycan from human seminal transferrin. 8011069 4 35 theme Bio-Gel 607:613 arg1 P-6 615:617 Bio-Gel P-6 607:617 Bio-Gel P-6 607:617 After ethanol precipitation and fractionation on Bio-Gel P-6 and Bio-Gel P-2, the oligosaccharide was further purified on Mono-Q and desalted on Bio-Gel P-2. 8011069 3 36 with digestion 441:449 arg1 F 488:488 PNGase F 481:488 PNGase F 481:488 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 3 36 with digestion 441:449 arg1 F 478:478 peptide N-glycosidase F 456:478 peptide N-glycosidase F (PNGase F) 456:489 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 5 37 dep [formula 841:848 arg1 see 851:853 see 851:853 see text 851:858 By 600-MHz 1H-NMR spectroscopy, the primary structure of the major N-linked oligosaccharide component was established to be: [formula: see text] 8011069 1 38 theme iron-containing 109:123 arg1 transferrin 84:94 Human seminal transferrin 70:94 Human seminal transferrin (HSmT) 70:101 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 1 38 theme iron-containing 109:123 arg1 glycoprotein 125:136 an iron-containing glycoprotein 106:136 an iron-containing glycoprotein whose structural properties have not been adequately investigated 106:202 Human seminal transferrin (HSmT) is an iron-containing glycoprotein whose structural properties have not been adequately investigated. 8011069 3 39 theme PNGase 481:486 arg1 F 488:488 PNGase F 481:488 PNGase F 481:488 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 3 39 theme PNGase 481:486 arg1 F 478:478 peptide N-glycosidase F 456:478 peptide N-glycosidase F (PNGase F) 456:489 The carbohydrate chains were released from the iron-free form by digestion with peptide N-glycosidase F (PNGase F) in the presence of detergents such as SDS and beta-octylglucoside. 8011069 0 40 theme seminal 49:55 arg1 transferrin 57:67 human seminal transferrin 43:67 human seminal transferrin 43:67 Primary structure of the major glycan from human seminal transferrin. 8011069 2 41 theme glycoprotein 246:257 arg1 content 222:228 The carbohydrate content 205:228 The carbohydrate content of the purified glycoprotein 205:257 The carbohydrate content of the purified glycoprotein amount to 6.1%, and monosaccharide analysis revealed the major oligosaccharide moiety to be of the N-glycoside type. 8011069 2 42 theme N-glycoside 358:368 arg1 type 370:373 the N-glycoside type 354:373 the N-glycoside type 354:373 The carbohydrate content of the purified glycoprotein amount to 6.1%, and monosaccharide analysis revealed the major oligosaccharide moiety to be of the N-glycoside type. 8011069 5 43 theme 600-MHz 719:725 arg1 spectroscopy 734:745 600-MHz 1H-NMR spectroscopy 719:745 600-MHz 1H-NMR spectroscopy 719:745 By 600-MHz 1H-NMR spectroscopy, the primary structure of the major N-linked oligosaccharide component was established to be: [formula: see text] 9751792 4 0 theme N- 720:721 arg1 elucidation 702:712 Structure elucidation 692:712 Structure elucidation of 14 N- and 2 O-glycans 692:737 Structure elucidation of 14 N- and 2 O-glycans was performed by 500 or 600 MHz1H-NMR spectroscopy. 9751792 0 1 theme O-glycans 53:61 arg1 Expression 0:9 Expression 0:9 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 0:142 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 0 2 theme carbohydrate 70:81 arg1 moiety 83:88 the carbohydrate moiety 66:88 the carbohydrate moiety of human amniotic fluid transferrin during pregnancy 66:141 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 0 3 from Expression 0:9 arg1 moiety 83:88 the carbohydrate moiety 66:88 the carbohydrate moiety of human amniotic fluid transferrin during pregnancy 66:141 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 0 4 link N-linked 14:21 arg1 x 33:33 x 33:33 x 33:33 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 0 4 link N-linked 14:21 arg1 Le 30:31 N-linked sialyl Le 14:31 N-linked sialyl Le(x) 14:34 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 3 5 theme alkaline 538:545 arg1 treatment 559:567 alkaline borohydride treatment 538:567 alkaline borohydride treatment of native hAFT 538:582 After alkaline borohydride treatment of native hAFT, the released O-glycans were isolated by gel filtration and fractionated by anion-exchange chroma-tography. 9751792 1 6 theme amniotic 233:240 arg1 fluid 242:246 amniotic fluid 233:246 amniotic fluid of a hydramniospatient 233:269 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 2 7 theme anion-exchange 501:514 arg1 chromatography 516:529 (high-pH) anion-exchange chromatography 491:529 (high-pH) anion-exchange chromatography 491:529 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 1 8 gly glycoprotein 159:170 arg1 glycoprotein 159:170 a glycoprotein 157:170 a glycoprotein involved in iron transport in body fluids 157:212 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 1 8 gly glycoprotein 159:170 arg1 Transferrin 144:154 Transferrin 144:154 Transferrin 144:154 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 3 9 theme borohydride 547:557 arg1 treatment 559:567 alkaline borohydride treatment 538:567 alkaline borohydride treatment of native hAFT 538:582 After alkaline borohydride treatment of native hAFT, the released O-glycans were isolated by gel filtration and fractionated by anion-exchange chroma-tography. 9751792 5 10 theme sialyl 939:944 arg1 x 949:949 x 949:949 x 949:949 Besides conventional N-glycans established earlier for human serum transferrin (hST), new (alpha1-3)-fucosylated N-glycans were found, representing sialyl Le(x) elements. 9751792 5 10 theme sialyl 939:944 arg1 Le 946:947 sialyl Le 939:947 sialyl Le(x) elements 939:959 Besides conventional N-glycans established earlier for human serum transferrin (hST), new (alpha1-3)-fucosylated N-glycans were found, representing sialyl Le(x) elements. 9751792 6 11 theme alpha1-6 1015:1022 arg1 -fucosylation 1024:1036 (alpha1-6)-fucosylation 1014:1036 (alpha1-6)-fucosylation 1014:1036 Furthermore, as compared to hST, a higher degree of (alpha1-6)-fucosylation and an increase in branching from di- to triantennary compounds has been detected. 9751792 4 12 theme Structure 692:700 arg1 elucidation 702:712 Structure elucidation 692:712 Structure elucidation of 14 N- and 2 O-glycans 692:737 Structure elucidation of 14 N- and 2 O-glycans was performed by 500 or 600 MHz1H-NMR spectroscopy. 9751792 5 13 theme conventional 799:810 arg1 N-glycans 812:820 conventional N-glycans 799:820 conventional N-glycans established earlier for human serum transferrin (hST) 799:874 Besides conventional N-glycans established earlier for human serum transferrin (hST), new (alpha1-3)-fucosylated N-glycans were found, representing sialyl Le(x) elements. 9751792 2 14 theme high-pH 492:498 arg1 chromatography 516:529 (high-pH) anion-exchange chromatography 491:529 (high-pH) anion-exchange chromatography 491:529 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 5 15 theme Le 946:947 arg1 elements 952:959 sialyl Le(x) elements 939:959 sialyl Le(x) elements 939:959 Besides conventional N-glycans established earlier for human serum transferrin (hST), new (alpha1-3)-fucosylated N-glycans were found, representing sialyl Le(x) elements. 9751792 2 16 theme gel 456:458 arg1 filtration 460:469 gel filtration 456:469 gel filtration 456:469 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 3 17 theme native 572:577 arg1 hAFT 579:582 native hAFT 572:582 native hAFT 572:582 After alkaline borohydride treatment of native hAFT, the released O-glycans were isolated by gel filtration and fractionated by anion-exchange chroma-tography. 9751792 7 18 theme O-glycans 1137:1145 arg1 presence 1125:1132 The presence 1121:1132 The presence of O-glycans 1121:1145 The presence of O-glycans is demonstrated for the first time in transferrin. 9751792 2 19 theme transferrin 373:383 arg1 N-glycans 339:347 The N-glycans 335:347 The N-glycans of human amniotic fluid transferrin (hAFT) 335:390 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 2 20 dep digestion 433:441 arg1 fractionated 475:486 fractionated 475:486 fractionated by (high-pH) anion-exchange chromatography 475:529 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 2 20 dep digestion 433:441 arg1 isolated 444:451 isolated 444:451 isolated by gel filtration 444:469 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 3 21 theme hAFT 579:582 arg1 treatment 559:567 alkaline borohydride treatment 538:567 alkaline borohydride treatment of native hAFT 538:582 After alkaline borohydride treatment of native hAFT, the released O-glycans were isolated by gel filtration and fractionated by anion-exchange chroma-tography. 9751792 4 22 theme MHz1H-NMR 767:775 arg1 spectroscopy 777:788 500 or 600 MHz1H-NMR spectroscopy 756:788 500 or 600 MHz1H-NMR spectroscopy 756:788 Structure elucidation of 14 N- and 2 O-glycans was performed by 500 or 600 MHz1H-NMR spectroscopy. 9751792 2 23 theme fluid 367:371 arg1 hAFT 386:389 hAFT 386:389 hAFT 386:389 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 2 23 theme fluid 367:371 arg1 transferrin 373:383 human amniotic fluid transferrin 352:383 human amniotic fluid transferrin (hAFT) 352:390 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 0 24 theme sialyl 23:28 arg1 x 33:33 x 33:33 x 33:33 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 0 24 theme sialyl 23:28 arg1 Le 30:31 N-linked sialyl Le 14:31 N-linked sialyl Le(x) 14:34 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 0 25 theme amniotic 99:106 arg1 transferrin 114:124 human amniotic fluid transferrin 93:124 human amniotic fluid transferrin 93:124 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 0 26 theme N-linked 14:21 arg1 x 33:33 x 33:33 x 33:33 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 0 26 theme N-linked 14:21 arg1 Le 30:31 N-linked sialyl Le 14:31 N-linked sialyl Le(x) 14:34 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 1 27 theme hydramniospatient 253:269 arg1 fluid 242:246 amniotic fluid 233:246 amniotic fluid of a hydramniospatient 233:269 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 0 28 theme human 93:97 arg1 transferrin 114:124 human amniotic fluid transferrin 93:124 human amniotic fluid transferrin 93:124 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 1 29 theme iron 184:187 arg1 transport 189:197 iron transport 184:197 iron transport in body fluids 184:212 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 0 30 theme transferrin 114:124 arg1 moiety 83:88 the carbohydrate moiety 66:88 the carbohydrate moiety of human amniotic fluid transferrin during pregnancy 66:141 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 3 31 theme released 589:596 arg1 O-glycans 598:606 the released O-glycans 585:606 the released O-glycans 585:606 After alkaline borohydride treatment of native hAFT, the released O-glycans were isolated by gel filtration and fractionated by anion-exchange chroma-tography. 9751792 6 32 theme -fucosylation 1024:1036 arg1 increase 1045:1052 an increase 1042:1052 an increase in branching from di- to triantennary compounds 1042:1100 Furthermore, as compared to hST, a higher degree of (alpha1-6)-fucosylation and an increase in branching from di- to triantennary compounds has been detected. 9751792 6 32 theme -fucosylation 1024:1036 arg1 degree 1004:1009 a higher degree 995:1009 a higher degree of (alpha1-6)-fucosylation 995:1036 Furthermore, as compared to hST, a higher degree of (alpha1-6)-fucosylation and an increase in branching from di- to triantennary compounds has been detected. 9751792 0 33 theme Le 30:31 arg1 Expression 0:9 Expression 0:9 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 0:142 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 1 34 theme sequential 274:283 arg1 chromatography 300:313 sequential anion-exchange chromatography 274:313 sequential anion-exchange chromatography 274:313 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 0 35 theme fluid 108:112 arg1 transferrin 114:124 human amniotic fluid transferrin 93:124 human amniotic fluid transferrin 93:124 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 2 36 theme PNGase-F 424:431 arg1 digestion 433:441 PNGase-F digestion 424:441 PNGase-F digestion 424:441 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 1 37 from transport 189:197 arg1 fluids 207:212 body fluids 202:212 body fluids 202:212 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 5 38 theme human 846:850 arg1 hST 871:873 hST 871:873 hST 871:873 Besides conventional N-glycans established earlier for human serum transferrin (hST), new (alpha1-3)-fucosylated N-glycans were found, representing sialyl Le(x) elements. 9751792 5 38 theme human 846:850 arg1 transferrin 858:868 human serum transferrin 846:868 human serum transferrin (hST) 846:874 Besides conventional N-glycans established earlier for human serum transferrin (hST), new (alpha1-3)-fucosylated N-glycans were found, representing sialyl Le(x) elements. 9751792 1 39 theme anion-exchange 285:298 arg1 chromatography 300:313 sequential anion-exchange chromatography 274:313 sequential anion-exchange chromatography 274:313 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 5 40 gly -fucosylated 891:902 arg1 N-glycans 904:912 new (alpha1-3)-fucosylated N-glycans 877:912 new (alpha1-3)-fucosylated N-glycans 877:912 Besides conventional N-glycans established earlier for human serum transferrin (hST), new (alpha1-3)-fucosylated N-glycans were found, representing sialyl Le(x) elements. 9751792 3 41 theme gel 625:627 arg1 filtration 629:638 gel filtration 625:638 gel filtration 625:638 After alkaline borohydride treatment of native hAFT, the released O-glycans were isolated by gel filtration and fractionated by anion-exchange chroma-tography. 9751792 7 42 from time 1177:1180 arg1 transferrin 1185:1195 transferrin 1185:1195 transferrin 1185:1195 The presence of O-glycans is demonstrated for the first time in transferrin. 9751792 0 43 dep Le 30:31 arg1 determinants 36:47 determinants 36:47 determinants 36:47 Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy. 9751792 6 44 theme triantennary 1079:1090 arg1 compounds 1092:1100 triantennary compounds 1079:1100 triantennary compounds 1079:1100 Furthermore, as compared to hST, a higher degree of (alpha1-6)-fucosylation and an increase in branching from di- to triantennary compounds has been detected. 9751792 1 45 theme body 202:205 arg1 fluids 207:212 body fluids 202:212 body fluids 202:212 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 3 46 theme anion-exchange 660:673 arg1 chroma-tography 675:689 anion-exchange chroma-tography 660:689 anion-exchange chroma-tography 660:689 After alkaline borohydride treatment of native hAFT, the released O-glycans were isolated by gel filtration and fractionated by anion-exchange chroma-tography. 9751792 1 47 attach isolated 219:226 arg2 Transferrin 144:154 Transferrin 144:154 Transferrin 144:154 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 1 47 attach isolated 219:226 arg2 glycoprotein 159:170 a glycoprotein 157:170 a glycoprotein involved in iron transport in body fluids 157:212 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 1 47 attach isolated 219:226 arg1 fluid 242:246 amniotic fluid 233:246 amniotic fluid of a hydramniospatient 233:269 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 4 48 theme O-glycans 729:737 arg1 elucidation 702:712 Structure elucidation 692:712 Structure elucidation of 14 N- and 2 O-glycans 692:737 Structure elucidation of 14 N- and 2 O-glycans was performed by 500 or 600 MHz1H-NMR spectroscopy. 9751792 6 49 theme higher 997:1002 arg1 degree 1004:1009 a higher degree 995:1009 a higher degree of (alpha1-6)-fucosylation 995:1036 Furthermore, as compared to hST, a higher degree of (alpha1-6)-fucosylation and an increase in branching from di- to triantennary compounds has been detected. 9751792 5 50 theme -fucosylated 891:902 arg1 N-glycans 904:912 new (alpha1-3)-fucosylated N-glycans 877:912 new (alpha1-3)-fucosylated N-glycans 877:912 Besides conventional N-glycans established earlier for human serum transferrin (hST), new (alpha1-3)-fucosylated N-glycans were found, representing sialyl Le(x) elements. 9751792 2 51 theme amniotic 358:365 arg1 hAFT 386:389 hAFT 386:389 hAFT 386:389 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 2 51 theme amniotic 358:365 arg1 transferrin 373:383 human amniotic fluid transferrin 352:383 human amniotic fluid transferrin (hAFT) 352:390 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 1 52 theme gel 319:321 arg1 filtration 323:332 gel filtration 319:332 gel filtration 319:332 Transferrin, a glycoprotein involved in iron transport in body fluids, was isolated from amniotic fluid of a hydramniospatient by sequential anion-exchange chromatography and gel filtration. 9751792 5 53 theme serum 852:856 arg1 hST 871:873 hST 871:873 hST 871:873 Besides conventional N-glycans established earlier for human serum transferrin (hST), new (alpha1-3)-fucosylated N-glycans were found, representing sialyl Le(x) elements. 9751792 5 53 theme serum 852:856 arg1 transferrin 858:868 human serum transferrin 846:868 human serum transferrin (hST) 846:874 Besides conventional N-glycans established earlier for human serum transferrin (hST), new (alpha1-3)-fucosylated N-glycans were found, representing sialyl Le(x) elements. 9751792 2 54 theme human 352:356 arg1 hAFT 386:389 hAFT 386:389 hAFT 386:389 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 2 54 theme human 352:356 arg1 transferrin 373:383 human amniotic fluid transferrin 352:383 human amniotic fluid transferrin (hAFT) 352:390 The N-glycans of human amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F digestion, isolated by gel filtration and fractionated by (high-pH) anion-exchange chromatography. 9751792 7 55 theme first 1171:1175 arg1 time 1177:1180 the first time 1167:1180 the first time in transferrin 1167:1195 The presence of O-glycans is demonstrated for the first time in transferrin. 10816579 3 0 theme parental 746:753 arg1 cells 755:759 the parental cells 742:759 the parental cells 742:759 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 6 1 theme bisecting 1094:1102 arg1 GlcNAc 1104:1109 bisecting GlcNAc 1094:1109 bisecting GlcNAc addition to the sugar chains of IgM 1094:1145 The extent of bisecting GlcNAc addition to the sugar chains of IgM was significantly correlated with the level of intracellular beta-1,4-GalT activity relative to that of GnT-III. 10816579 1 2 theme GlcNAc 136:141 arg1 formation 113:121 the formation 109:121 the formation of bisecting GlcNAc 109:141 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 3 3 from half 729:732 arg1 cells 755:759 the parental cells 742:759 the parental cells 742:759 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 1 4 dep GnT-III 275:281 arg1 UDP-N-acetylglucosamine 284:306 UDP-N-acetylglucosamine 284:306 UDP-N-acetylglucosamine 284:306 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 1 4 dep GnT-III 275:281 arg1 4-N-acetylglucosaminyltransferase 333:365 4-N-acetylglucosaminyltransferase 333:365 4-N-acetylglucosaminyltransferase 333:365 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 3 5 theme beta-1,4-GalT-I-single 558:579 arg1 cells 590:594 the beta-1,4-GalT-I-single knockout cells 554:594 the beta-1,4-GalT-I-single knockout cells 554:594 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 3 6 theme GlcNAc 621:626 arg1 addition 628:635 bisecting GlcNAc addition 611:635 bisecting GlcNAc addition to the sugar chains of IgM 611:662 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 3 7 theme addition 628:635 arg1 extent 601:606 the extent 597:606 the extent of bisecting GlcNAc addition to the sugar chains of IgM 597:662 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 6 8 theme intracellular 1194:1206 arg1 activity 1222:1229 intracellular beta-1,4-GalT activity 1194:1229 intracellular beta-1,4-GalT activity relative to that of GnT-III 1194:1257 The extent of bisecting GlcNAc addition to the sugar chains of IgM was significantly correlated with the level of intracellular beta-1,4-GalT activity relative to that of GnT-III. 10816579 3 9 dep half 729:732 arg1 that 734:737 that 734:737 that 734:737 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 3 10 theme GnT-III 766:772 arg1 activity 774:781 GnT-III activity 766:781 GnT-III activity 766:781 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 6 11 theme sugar 1127:1131 arg1 chains 1133:1138 the sugar chains 1123:1138 the sugar chains of IgM 1123:1145 The extent of bisecting GlcNAc addition to the sugar chains of IgM was significantly correlated with the level of intracellular beta-1,4-GalT activity relative to that of GnT-III. 10816579 6 12 theme relative 1231:1238 arg1 activity 1222:1229 intracellular beta-1,4-GalT activity 1194:1229 intracellular beta-1,4-GalT activity relative to that of GnT-III 1194:1257 The extent of bisecting GlcNAc addition to the sugar chains of IgM was significantly correlated with the level of intracellular beta-1,4-GalT activity relative to that of GnT-III. 10816579 2 13 theme B 434:434 arg1 clone 441:445 a beta-1,4-GalT-I single knockout human B cell clone 394:445 a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III 394:548 We isolated a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III. 10816579 5 14 theme GnT-III 952:958 arg1 transfectants 960:972 the GnT-III transfectants 948:972 the GnT-III transfectants 948:972 In the GnT-III transfectants, the extent of bisecting GlcNAc addition increased along with the increase in levels of GnT-III activity. 10816579 5 15 theme addition 1006:1013 arg1 extent 979:984 the extent 975:984 the extent of bisecting GlcNAc addition 975:1013 In the GnT-III transfectants, the extent of bisecting GlcNAc addition increased along with the increase in levels of GnT-III activity. 10816579 4 16 theme beta-1,4-GalT-I 805:819 arg1 transfectants 821:833 the beta-1,4-GalT-I transfectants 801:833 the beta-1,4-GalT-I transfectants 801:833 In the beta-1,4-GalT-I transfectants, the extent of bisecting GlcNAc addition was reduced although GnT-III activity was not altered significantly. 10816579 5 17 from increase 1040:1047 arg1 levels 1052:1057 levels 1052:1057 levels of GnT-III activity 1052:1077 In the GnT-III transfectants, the extent of bisecting GlcNAc addition increased along with the increase in levels of GnT-III activity. 10816579 2 18 theme human 428:432 arg1 clone 441:445 a beta-1,4-GalT-I single knockout human B cell clone 394:445 a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III 394:548 We isolated a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III. 10816579 2 19 theme transfectant 484:495 arg1 clones 497:502 several transfectant clones 476:502 several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III 476:548 We isolated a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III. 10816579 6 20 theme beta-1,4-GalT 1208:1220 arg1 activity 1222:1229 intracellular beta-1,4-GalT activity 1194:1229 intracellular beta-1,4-GalT activity relative to that of GnT-III 1194:1257 The extent of bisecting GlcNAc addition to the sugar chains of IgM was significantly correlated with the level of intracellular beta-1,4-GalT activity relative to that of GnT-III. 10816579 0 21 link N-linked 40:47 arg1 chains 55:60 N-linked sugar chains 40:60 N-linked sugar chains 40:60 Control of bisecting GlcNAc addition to N-linked sugar chains. 10816579 1 22 theme present 70:76 arg1 study 78:82 the present study 66:82 the present study 66:82 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 2 23 theme knockout 419:426 arg1 clone 441:445 a beta-1,4-GalT-I single knockout human B cell clone 394:445 a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III 394:548 We isolated a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III. 10816579 2 24 theme several 476:482 arg1 clones 497:502 several transfectant clones 476:502 several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III 476:548 We isolated a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III. 10816579 4 25 theme GnT-III 897:903 arg1 activity 905:912 GnT-III activity 897:912 GnT-III activity 897:912 In the beta-1,4-GalT-I transfectants, the extent of bisecting GlcNAc addition was reduced although GnT-III activity was not altered significantly. 10816579 5 26 theme bisecting 989:997 arg1 addition 1006:1013 bisecting GlcNAc addition 989:1013 bisecting GlcNAc addition 989:1013 In the GnT-III transfectants, the extent of bisecting GlcNAc addition increased along with the increase in levels of GnT-III activity. 10816579 2 27 theme single 412:417 arg1 clone 441:445 a beta-1,4-GalT-I single knockout human B cell clone 394:445 a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III 394:548 We isolated a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III. 10816579 0 28 theme GlcNAc 21:26 arg1 addition 28:35 bisecting GlcNAc addition 11:35 bisecting GlcNAc addition 11:35 Control of bisecting GlcNAc addition to N-linked sugar chains. 10816579 4 29 theme addition 867:874 arg1 extent 840:845 the extent 836:845 the extent of bisecting GlcNAc addition 836:874 In the beta-1,4-GalT-I transfectants, the extent of bisecting GlcNAc addition was reduced although GnT-III activity was not altered significantly. 10816579 3 30 theme bisecting 611:619 arg1 addition 628:635 bisecting GlcNAc addition 611:635 bisecting GlcNAc addition to the sugar chains of IgM 611:662 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 5 31 theme GnT-III 1062:1068 arg1 activity 1070:1077 GnT-III activity 1062:1077 GnT-III activity 1062:1077 In the GnT-III transfectants, the extent of bisecting GlcNAc addition increased along with the increase in levels of GnT-III activity. 10816579 2 32 theme monoclonal 457:466 arg1 IgM 468:470 monoclonal IgM 457:470 monoclonal IgM 457:470 We isolated a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III. 10816579 0 33 theme bisecting 11:19 arg1 addition 28:35 bisecting GlcNAc addition 11:35 bisecting GlcNAc addition 11:35 Control of bisecting GlcNAc addition to N-linked sugar chains. 10816579 1 34 theme experimental 85:96 arg1 control 98:104 experimental control 85:104 experimental control of the formation of bisecting GlcNAc 85:141 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 3 35 theme knockout 581:588 arg1 cells 590:594 the beta-1,4-GalT-I-single knockout cells 554:594 the beta-1,4-GalT-I-single knockout cells 554:594 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 4 36 theme GlcNAc 860:865 arg1 addition 867:874 bisecting GlcNAc addition 850:874 bisecting GlcNAc addition 850:874 In the beta-1,4-GalT-I transfectants, the extent of bisecting GlcNAc addition was reduced although GnT-III activity was not altered significantly. 10816579 6 37 theme addition 1111:1118 arg1 extent 1084:1089 The extent 1080:1089 The extent of bisecting GlcNAc addition to the sugar chains of IgM 1080:1145 The extent of bisecting GlcNAc addition to the sugar chains of IgM was significantly correlated with the level of intracellular beta-1,4-GalT activity relative to that of GnT-III. 10816579 0 38 theme addition 28:35 arg1 Control 0:6 Control 0:6 Control of bisecting GlcNAc addition to N-linked sugar chains. 0:61 Control of bisecting GlcNAc addition to N-linked sugar chains. 10816579 1 39 theme beta-d-mannoside 308:323 arg1 beta-1 325:330 beta-d-mannoside beta-1 308:330 beta-d-mannoside beta-1 308:330 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 1 40 dep UDP-galactose 204:216 arg1 beta-1 238:243 N-acetylglucosamine beta-1 218:243 N-acetylglucosamine beta-1 218:243 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 4 41 theme bisecting 850:858 arg1 addition 867:874 bisecting GlcNAc addition 850:874 bisecting GlcNAc addition 850:874 In the beta-1,4-GalT-I transfectants, the extent of bisecting GlcNAc addition was reduced although GnT-III activity was not altered significantly. 10816579 2 42 theme cell 436:439 arg1 clone 441:445 a beta-1,4-GalT-I single knockout human B cell clone 394:445 a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III 394:548 We isolated a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III. 10816579 0 43 theme sugar 49:53 arg1 chains 55:60 N-linked sugar chains 40:60 N-linked sugar chains 40:60 Control of bisecting GlcNAc addition to N-linked sugar chains. 10816579 3 44 theme beta-1,4-GalT 685:697 arg1 activity 699:706 beta-1,4-GalT activity 685:706 beta-1,4-GalT activity 685:706 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 7 45 from substrate 1351:1359 arg1 cells 1368:1372 the cells 1364:1372 the cells 1364:1372 These results were interpreted as indicating that beta-1, 4-GalT competes with GnT-III for substrate in the cells. 10816579 0 46 theme N-linked 40:47 arg1 chains 55:60 N-linked sugar chains 40:60 N-linked sugar chains 40:60 Control of bisecting GlcNAc addition to N-linked sugar chains. 10816579 3 47 theme sugar 644:648 arg1 chains 650:655 the sugar chains 640:655 the sugar chains of IgM 640:662 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 1 48 dep beta-1,4-GalT 189:201 arg1 4-galactosyltransferase 246:268 4-galactosyltransferase 246:268 4-galactosyltransferase 246:268 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 1 48 dep beta-1,4-GalT 189:201 arg1 UDP-galactose 204:216 UDP-galactose 204:216 UDP-galactose 204:216 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 5 49 theme activity 1070:1077 arg1 levels 1052:1057 levels 1052:1057 levels of GnT-III activity 1052:1077 In the GnT-III transfectants, the extent of bisecting GlcNAc addition increased along with the increase in levels of GnT-III activity. 10816579 5 50 theme GlcNAc 999:1004 arg1 addition 1006:1013 bisecting GlcNAc addition 989:1013 bisecting GlcNAc addition 989:1013 In the GnT-III transfectants, the extent of bisecting GlcNAc addition increased along with the increase in levels of GnT-III activity. 10816579 6 51 theme activity 1222:1229 arg1 level 1185:1189 the level 1181:1189 the level of intracellular beta-1,4-GalT activity relative to that of GnT-III 1181:1257 The extent of bisecting GlcNAc addition to the sugar chains of IgM was significantly correlated with the level of intracellular beta-1,4-GalT activity relative to that of GnT-III. 10816579 1 52 theme formation 113:121 arg1 control 98:104 experimental control 85:104 experimental control of the formation of bisecting GlcNAc 85:141 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 6 53 theme IgM 1143:1145 arg1 chains 1133:1138 the sugar chains 1123:1138 the sugar chains of IgM 1123:1145 The extent of bisecting GlcNAc addition to the sugar chains of IgM was significantly correlated with the level of intracellular beta-1,4-GalT activity relative to that of GnT-III. 10816579 3 54 theme IgM 660:662 arg1 chains 650:655 the sugar chains 640:655 the sugar chains of IgM 640:662 In the beta-1,4-GalT-I-single knockout cells, the extent of bisecting GlcNAc addition to the sugar chains of IgM was increased, where beta-1,4-GalT activity was reduced to about half that in the parental cells, and GnT-III activity was unaltered. 10816579 6 55 theme GlcNAc 1104:1109 arg1 addition 1111:1118 bisecting GlcNAc addition 1094:1118 bisecting GlcNAc addition to the sugar chains of IgM 1094:1145 The extent of bisecting GlcNAc addition to the sugar chains of IgM was significantly correlated with the level of intracellular beta-1,4-GalT activity relative to that of GnT-III. 10816579 2 56 theme beta-1,4-GalT-I 396:410 arg1 clone 441:445 a beta-1,4-GalT-I single knockout human B cell clone 394:445 a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III 394:548 We isolated a beta-1,4-GalT-I single knockout human B cell clone producing monoclonal IgM and several transfectant clones that overexpressed beta-1,4-GalT-I or GnT-III. 10816579 1 57 theme N-acetylglucosamine 218:236 arg1 beta-1 238:243 N-acetylglucosamine beta-1 218:243 N-acetylglucosamine beta-1 218:243 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 1 58 dep UDP-N-acetylglucosamine 284:306 arg1 beta-1 325:330 beta-d-mannoside beta-1 308:330 beta-d-mannoside beta-1 308:330 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 10816579 1 59 theme bisecting 126:134 arg1 GlcNAc 136:141 bisecting GlcNAc 126:141 bisecting GlcNAc 126:141 In the present study, experimental control of the formation of bisecting GlcNAc was investigated, and the competition between beta-1,4-GalT (UDP-galactose:N-acetylglucosamine beta-1, 4-galactosyltransferase) and GnT-III (UDP-N-acetylglucosamine:beta-d-mannoside beta-1, 4-N-acetylglucosaminyltransferase) was examined. 9654101 6 0 theme type-2 1305:1310 arg1 monosialylpentasaccharides 1312:1337 core type-2 monosialylpentasaccharides 1300:1337 20% core type-2 monosialylpentasaccharides 1296:1337 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 2 1 theme blood 643:647 arg1 leukocytes 649:658 Sendai-virus-induced human peripheral blood leukocytes 605:658 Sendai-virus-induced human peripheral blood leukocytes 605:658 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 4 2 theme ionisation 953:962 arg1 spectrometry 984:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 4 3 link O-linked 760:767 arg1 chains 769:774 the O-linked chains 756:774 the O-linked chains of IFN-alpha2b 756:789 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 4 4 theme of 969:970 arg1 spectrometry 984:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 2 5 theme peripheral 632:641 arg1 leukocytes 649:658 Sendai-virus-induced human peripheral blood leukocytes 605:658 Sendai-virus-induced human peripheral blood leukocytes 605:658 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 0 6 link N-linked 31:38 arg1 oligosaccharides 53:68 N-linked and O-linked oligosaccharides 31:68 N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c 31:124 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 5 7 theme alpha1,3-linked 1123:1137 arg1 unit 1146:1149 an additional alpha1,3-linked fucose unit 1109:1149 an additional alpha1,3-linked fucose unit 1109:1149 The IFN-alpha14c N-glycans were shown to exhibit core-fucosylated biantennary glycans, with about 10% carrying an additional alpha1,3-linked fucose unit at the antennae. 9654101 1 8 theme preparation 315:325 arg1 components 254:263 the components 250:263 the components of a highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus-induced human peripheral blood leukocytes 250:392 We have previously isolated and partially characterised the components of a highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 6 9 theme type-1 1260:1265 arg1 monosialyltrisaccharides 1267:1290 core type-1 monosialyltrisaccharides 1255:1290 30% core type-1 monosialyltrisaccharides 1251:1290 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 2 10 gly glycosylated 469:480 arg1 two 439:441 two 439:441 two 439:441 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 2 10 gly glycosylated 469:480 arg1 these 446:450 these 446:450 these 446:450 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 6 11 theme type-1 1218:1223 arg1 disialyltetrasaccharides 1225:1248 core type-1 disialyltetrasaccharides 1213:1248 about 50% core type-1 disialyltetrasaccharides 1203:1248 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 4 12 link N-linked 710:717 arg1 oligosaccharides 719:734 the N-linked oligosaccharides 706:734 the N-linked oligosaccharides of IFN-alpha14c 706:750 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 2 13 theme Sendai-virus-induced 605:624 arg1 leukocytes 649:658 Sendai-virus-induced human peripheral blood leukocytes 605:658 Sendai-virus-induced human peripheral blood leukocytes 605:658 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 4 14 theme IFN-alpha2b 779:789 arg1 chains 769:774 the O-linked chains 756:774 the O-linked chains of IFN-alpha2b 756:789 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 4 14 theme IFN-alpha2b 779:789 arg1 oligosaccharides 719:734 the N-linked oligosaccharides 706:734 the N-linked oligosaccharides of IFN-alpha14c 706:750 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 0 15 theme human 159:163 arg1 leukocytes 182:191 Sendai-virus-induced human peripheral blood leukocytes 138:191 Sendai-virus-induced human peripheral blood leukocytes 138:191 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 4 16 theme O-linked 760:767 arg1 chains 769:774 the O-linked chains 756:774 the O-linked chains of IFN-alpha2b 756:789 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 0 17 theme Sendai-virus-induced 138:157 arg1 leukocytes 182:191 Sendai-virus-induced human peripheral blood leukocytes 138:191 Sendai-virus-induced human peripheral blood leukocytes 138:191 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 4 18 theme matrix-assisted 920:934 arg1 spectrometry 984:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 4 19 theme N-linked 710:717 arg1 oligosaccharides 719:734 the N-linked oligosaccharides 706:734 the N-linked oligosaccharides of IFN-alpha14c 706:750 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 6 20 theme core 1213:1216 arg1 disialyltetrasaccharides 1225:1248 core type-1 disialyltetrasaccharides 1213:1248 about 50% core type-1 disialyltetrasaccharides 1203:1248 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 4 21 theme glycosidase 884:894 arg1 digestions 896:905 specific glycosidase digestions 875:905 specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry 875:995 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 2 22 theme IFN-alpha 400:408 arg1 species 410:416 Nine IFN-alpha species 395:416 Nine IFN-alpha species 395:416 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 0 23 theme Structural 0:9 arg1 characterisation 11:26 Structural characterisation 0:26 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c 0:124 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 1 24 theme Sendai-virus-induced 339:358 arg1 leukocytes 383:392 Sendai-virus-induced human peripheral blood leukocytes 339:392 Sendai-virus-induced human peripheral blood leukocytes 339:392 We have previously isolated and partially characterised the components of a highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 4 25 theme specific 875:882 arg1 digestions 896:905 specific glycosidase digestions 875:905 specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry 875:995 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 0 26 link O-linked 44:51 arg1 oligosaccharides 53:68 N-linked and O-linked oligosaccharides 31:68 N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c 31:124 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 6 27 dep % 1211:1211 arg1 disialyltetrasaccharides 1225:1248 core type-1 disialyltetrasaccharides 1213:1248 about 50% core type-1 disialyltetrasaccharides 1203:1248 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 0 28 theme N-linked 31:38 arg1 oligosaccharides 53:68 N-linked and O-linked oligosaccharides 31:68 N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c 31:124 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 1 29 theme human 360:364 arg1 leukocytes 383:392 Sendai-virus-induced human peripheral blood leukocytes 339:392 Sendai-virus-induced human peripheral blood leukocytes 339:392 We have previously isolated and partially characterised the components of a highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 0 30 theme blood 176:180 arg1 leukocytes 182:191 Sendai-virus-induced human peripheral blood leukocytes 138:191 Sendai-virus-induced human peripheral blood leukocytes 138:191 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 0 31 attach derived 70:76 arg2 oligosaccharides 53:68 N-linked and O-linked oligosaccharides 31:68 N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c 31:124 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 0 31 attach derived 70:76 arg1 interferon-alpha2b 83:100 interferon-alpha2b 83:100 interferon-alpha2b 83:100 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 0 31 attach derived 70:76 arg1 interferon-alpha14c 106:124 interferon-alpha14c 106:124 interferon-alpha14c 106:124 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 5 32 theme IFN-alpha14c 1002:1013 arg1 N-glycans 1015:1023 The IFN-alpha14c N-glycans 998:1023 The IFN-alpha14c N-glycans 998:1023 The IFN-alpha14c N-glycans were shown to exhibit core-fucosylated biantennary glycans, with about 10% carrying an additional alpha1,3-linked fucose unit at the antennae. 9654101 6 33 theme core 1300:1303 arg1 monosialylpentasaccharides 1312:1337 core type-2 monosialylpentasaccharides 1300:1337 20% core type-2 monosialylpentasaccharides 1296:1337 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 2 34 theme A. 493:494 arg1 Biochem 661:667 Biochem 661:667 Biochem 661:667 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 2 34 theme A. 493:494 arg1 Identification 544:557 [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification 482:557 [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes 482:658 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 1 35 theme peripheral 366:375 arg1 leukocytes 383:392 Sendai-virus-induced human peripheral blood leukocytes 339:392 Sendai-virus-induced human peripheral blood leukocytes 339:392 We have previously isolated and partially characterised the components of a highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 0 36 theme peripheral 165:174 arg1 leukocytes 182:191 Sendai-virus-induced human peripheral blood leukocytes 138:191 Sendai-virus-induced human peripheral blood leukocytes 138:191 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 5 37 theme fucose 1139:1144 arg1 unit 1146:1149 an additional alpha1,3-linked fucose unit 1109:1149 an additional alpha1,3-linked fucose unit 1109:1149 The IFN-alpha14c N-glycans were shown to exhibit core-fucosylated biantennary glycans, with about 10% carrying an additional alpha1,3-linked fucose unit at the antennae. 9654101 6 38 dep % 1298:1298 arg1 monosialylpentasaccharides 1312:1337 core type-2 monosialylpentasaccharides 1300:1337 20% core type-2 monosialylpentasaccharides 1296:1337 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 0 39 theme O-linked 44:51 arg1 oligosaccharides 53:68 N-linked and O-linked oligosaccharides 31:68 N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c 31:124 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 1 40 theme blood 377:381 arg1 leukocytes 383:392 Sendai-virus-induced human peripheral blood leukocytes 339:392 Sendai-virus-induced human peripheral blood leukocytes 339:392 We have previously isolated and partially characterised the components of a highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 4 41 theme tandem 843:848 arg1 spectrometry 855:866 electrospray tandem mass spectrometry 830:866 electrospray tandem mass spectrometry 830:866 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 5 42 gly core-fucosylated 1047:1062 arg1 glycans 1076:1082 core-fucosylated biantennary glycans 1047:1082 core-fucosylated biantennary glycans 1047:1082 The IFN-alpha14c N-glycans were shown to exhibit core-fucosylated biantennary glycans, with about 10% carrying an additional alpha1,3-linked fucose unit at the antennae. 9654101 4 43 theme mass 979:982 arg1 spectrometry 984:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 4 44 theme electrospray 830:841 arg1 spectrometry 855:866 electrospray tandem mass spectrometry 830:866 electrospray tandem mass spectrometry 830:866 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 4 45 theme desorption 942:951 arg1 spectrometry 984:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 6 46 contain carry 1197:1201 arg2 % 1253:1253 30% 1251:1253 30% core type-1 monosialyltrisaccharides 1251:1290 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 6 46 contain carry 1197:1201 arg2 % 1298:1298 20% 1296:1298 20% core type-2 monosialylpentasaccharides 1296:1337 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 6 46 contain carry 1197:1201 arg1 IFN-alpha2b 1172:1182 The IFN-alpha2b 1168:1182 The IFN-alpha2b 1168:1182 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 6 46 contain carry 1197:1201 arg2 % 1211:1211 about 50% 1203:1211 about 50% core type-1 disialyltetrasaccharides 1203:1248 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 4 47 theme time 964:967 arg1 spectrometry 984:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 0 48 theme oligosaccharides 53:68 arg1 characterisation 11:26 Structural characterisation 0:26 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c 0:124 Structural characterisation of N-linked and O-linked oligosaccharides derived from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 4 49 theme laser 936:940 arg1 spectrometry 984:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 5 50 contain carrying 1100:1107 arg2 unit 1146:1149 an additional alpha1,3-linked fucose unit 1109:1149 an additional alpha1,3-linked fucose unit 1109:1149 The IFN-alpha14c N-glycans were shown to exhibit core-fucosylated biantennary glycans, with about 10% carrying an additional alpha1,3-linked fucose unit at the antennae. 9654101 5 50 contain carrying 1100:1107 arg1 % 1098:1098 about 10% 1090:1098 about 10% carrying an additional alpha1,3-linked fucose unit at the antennae 1090:1165 The IFN-alpha14c N-glycans were shown to exhibit core-fucosylated biantennary glycans, with about 10% carrying an additional alpha1,3-linked fucose unit at the antennae. 9654101 4 51 theme mass 850:853 arg1 spectrometry 855:866 electrospray tandem mass spectrometry 830:866 electrospray tandem mass spectrometry 830:866 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 2 52 theme human 626:630 arg1 leukocytes 649:658 Sendai-virus-induced human peripheral blood leukocytes 605:658 Sendai-virus-induced human peripheral blood leukocytes 605:658 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 2 53 theme subtypes 584:591 arg1 Biochem 661:667 Biochem 661:667 Biochem 661:667 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 2 53 theme subtypes 584:591 arg1 Identification 544:557 [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification 482:557 [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes 482:658 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 5 54 theme core-fucosylated 1047:1062 arg1 glycans 1076:1082 core-fucosylated biantennary glycans 1047:1082 core-fucosylated biantennary glycans 1047:1082 The IFN-alpha14c N-glycans were shown to exhibit core-fucosylated biantennary glycans, with about 10% carrying an additional alpha1,3-linked fucose unit at the antennae. 9654101 5 55 link alpha1,3-linked 1123:1137 arg1 unit 1146:1149 an additional alpha1,3-linked fucose unit 1109:1149 an additional alpha1,3-linked fucose unit 1109:1149 The IFN-alpha14c N-glycans were shown to exhibit core-fucosylated biantennary glycans, with about 10% carrying an additional alpha1,3-linked fucose unit at the antennae. 9654101 1 56 theme purified 277:284 arg1 preparation 315:325 a highly purified interferon-alpha (IFN-alpha) preparation 268:325 a highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus-induced human peripheral blood leukocytes 268:392 We have previously isolated and partially characterised the components of a highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 2 57 theme interferon-alpha 567:582 arg1 subtypes 584:591 nine interferon-alpha subtypes 562:591 nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes 562:658 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 5 58 theme additional 1112:1121 arg1 unit 1146:1149 an additional alpha1,3-linked fucose unit 1109:1149 an additional alpha1,3-linked fucose unit 1109:1149 The IFN-alpha14c N-glycans were shown to exhibit core-fucosylated biantennary glycans, with about 10% carrying an additional alpha1,3-linked fucose unit at the antennae. 9654101 5 59 theme biantennary 1064:1074 arg1 glycans 1076:1082 core-fucosylated biantennary glycans 1047:1082 core-fucosylated biantennary glycans 1047:1082 The IFN-alpha14c N-glycans were shown to exhibit core-fucosylated biantennary glycans, with about 10% carrying an additional alpha1,3-linked fucose unit at the antennae. 9654101 4 60 theme IFN-alpha14c 739:750 arg1 chains 769:774 the O-linked chains 756:774 the O-linked chains of IFN-alpha2b 756:789 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 4 60 theme IFN-alpha14c 739:750 arg1 oligosaccharides 719:734 the N-linked oligosaccharides 706:734 the N-linked oligosaccharides of IFN-alpha14c 706:750 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 1 61 theme interferon-alpha 286:301 arg1 preparation 315:325 a highly purified interferon-alpha (IFN-alpha) preparation 268:325 a highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus-induced human peripheral blood leukocytes 268:392 We have previously isolated and partially characterised the components of a highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus-induced human peripheral blood leukocytes. 9654101 4 62 theme flight 972:977 arg1 spectrometry 984:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 matrix-assisted laser desorption ionisation time of flight mass spectrometry 920:995 Here, we isolated the N-linked oligosaccharides of IFN-alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were characterised by electrospray tandem mass spectrometry and by specific glycosidase digestions monitored by matrix-assisted laser desorption ionisation time of flight mass spectrometry. 9654101 6 63 theme core 1255:1258 arg1 monosialyltrisaccharides 1267:1290 core type-1 monosialyltrisaccharides 1255:1290 30% core type-1 monosialyltrisaccharides 1251:1290 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 9654101 2 64 theme these 446:450 arg1 two 439:441 two 439:441 two 439:441 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 2 64 theme these 446:450 arg1 these 446:450 these 446:450 these 446:450 Nine IFN-alpha species were identified, and two of these were found to be glycosylated [Nyman, T. A., Tölö, H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha subtypes produced by Sendai-virus-induced human peripheral blood leukocytes, Biochem. 9654101 6 65 dep % 1253:1253 arg1 monosialyltrisaccharides 1267:1290 core type-1 monosialyltrisaccharides 1255:1290 30% core type-1 monosialyltrisaccharides 1251:1290 The IFN-alpha2b was shown to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1 monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides. 7068558 4 0 theme oligosaccharides 517:532 arg1 study 504:508 A structural study 491:508 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis 491:642 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 2 1 attach released 225:232 arg1 samples 293:299 two lactoferrin samples 277:299 two lactoferrin samples of different races 277:318 These sugar chains were released as oligosaccharides by hydrazinolysis from two lactoferrin samples of different races. 7068558 2 1 attach released 225:232 arg2 chains 213:218 These sugar chains 201:218 These sugar chains 201:218 These sugar chains were released as oligosaccharides by hydrazinolysis from two lactoferrin samples of different races. 7068558 2 1 attach released 225:232 arg2 oligosaccharides 237:252 oligosaccharides 237:252 oligosaccharides 237:252 These sugar chains were released as oligosaccharides by hydrazinolysis from two lactoferrin samples of different races. 7068558 1 2 link asparagine-linked 155:171 arg1 chains 179:184 2 asparagine-linked sugar chains 153:184 2 asparagine-linked sugar chains 153:184 Human lactoferrin contains 2 asparagine-linked sugar chains in 1 molecule. 7068558 4 3 from digestion 593:601 arg1 combination 606:616 combination 606:616 combination with methylation analysis 606:642 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 1 4 theme asparagine-linked 155:171 arg1 chains 179:184 2 asparagine-linked sugar chains 153:184 2 asparagine-linked sugar chains 153:184 Human lactoferrin contains 2 asparagine-linked sugar chains in 1 molecule. 7068558 0 5 theme novel 75:79 arg1 chains 118:123 four novel complex-type asparagine-linked sugar chains 70:123 four novel complex-type asparagine-linked sugar chains 70:123 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 3 6 theme fractionation 377:389 arg1 pattern 391:397 exactly the same fractionation pattern 360:397 exactly the same fractionation pattern 360:397 The two oligosaccharide fractions gave exactly the same fractionation pattern upon paper electrophoresis and Bio-Gel P-4 column chromatography after sialidase digestion. 7068558 4 7 theme structural 493:502 arg1 study 504:508 A structural study 491:508 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis 491:642 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 4 8 theme moiety 765:770 arg1 quantity 737:744 quantity 737:744 quantity 737:744 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 4 8 theme moiety 765:770 arg1 quality 725:731 quality 725:731 quality 725:731 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 0 9 theme asparagine-linked 94:110 arg1 chains 118:123 four novel complex-type asparagine-linked sugar chains 70:123 four novel complex-type asparagine-linked sugar chains 70:123 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 2 10 theme lactoferrin 281:291 arg1 samples 293:299 two lactoferrin samples 277:299 two lactoferrin samples of different races 277:318 These sugar chains were released as oligosaccharides by hydrazinolysis from two lactoferrin samples of different races. 7068558 1 11 theme sugar 173:177 arg1 chains 179:184 2 asparagine-linked sugar chains 153:184 2 asparagine-linked sugar chains 153:184 Human lactoferrin contains 2 asparagine-linked sugar chains in 1 molecule. 7068558 0 12 theme complex-type 81:92 arg1 chains 118:123 four novel complex-type asparagine-linked sugar chains 70:123 four novel complex-type asparagine-linked sugar chains 70:123 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 1 13 contain contains 144:151 arg1 molecule 191:198 1 molecule 189:198 1 molecule 189:198 Human lactoferrin contains 2 asparagine-linked sugar chains in 1 molecule. 7068558 1 13 contain contains 144:151 arg2 chains 179:184 2 asparagine-linked sugar chains 153:184 2 asparagine-linked sugar chains 153:184 Human lactoferrin contains 2 asparagine-linked sugar chains in 1 molecule. 7068558 1 13 contain contains 144:151 arg1 lactoferrin 132:142 Human lactoferrin 126:142 Human lactoferrin 126:142 Human lactoferrin contains 2 asparagine-linked sugar chains in 1 molecule. 7068558 1 13 contain contains 144:151 arg2 lactoferrin 132:142 Human lactoferrin 126:142 Human lactoferrin 126:142 Human lactoferrin contains 2 asparagine-linked sugar chains in 1 molecule. 7068558 3 14 theme P-4 438:440 arg1 chromatography 449:462 Bio-Gel P-4 column chromatography 430:462 Bio-Gel P-4 column chromatography 430:462 The two oligosaccharide fractions gave exactly the same fractionation pattern upon paper electrophoresis and Bio-Gel P-4 column chromatography after sialidase digestion. 7068558 3 15 theme paper 404:408 arg1 electrophoresis 410:424 paper electrophoresis 404:424 paper electrophoresis 404:424 The two oligosaccharide fractions gave exactly the same fractionation pattern upon paper electrophoresis and Bio-Gel P-4 column chromatography after sialidase digestion. 7068558 3 16 theme oligosaccharide 329:343 arg1 fractions 345:353 The two oligosaccharide fractions 321:353 The two oligosaccharide fractions 321:353 The two oligosaccharide fractions gave exactly the same fractionation pattern upon paper electrophoresis and Bio-Gel P-4 column chromatography after sialidase digestion. 7068558 4 17 from difference 706:715 arg1 quantity 737:744 quantity 737:744 quantity 737:744 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 4 17 from difference 706:715 arg1 quality 725:731 quality 725:731 quality 725:731 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 0 18 theme Structural 0:9 arg1 study 11:15 Structural study 0:15 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 0:124 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 4 19 theme lactoferrin 775:785 arg1 moiety 765:770 the sugar chain moiety 749:770 the sugar chain moiety of lactoferrin 749:785 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 0 20 theme chains 118:123 arg1 finding 59:65 finding 59:65 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 0:124 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 2 21 theme races 314:318 arg1 samples 293:299 two lactoferrin samples 277:299 two lactoferrin samples of different races 277:318 These sugar chains were released as oligosaccharides by hydrazinolysis from two lactoferrin samples of different races. 7068558 4 22 with combination 606:616 arg1 analysis 635:642 methylation analysis 623:642 methylation analysis 623:642 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 4 23 theme methylation 623:633 arg1 analysis 635:642 methylation analysis 623:642 methylation analysis 623:642 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 0 24 theme sugar 112:116 arg1 chains 118:123 four novel complex-type asparagine-linked sugar chains 70:123 four novel complex-type asparagine-linked sugar chains 70:123 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 2 25 theme different 304:312 arg1 races 314:318 different races 304:318 different races 304:318 These sugar chains were released as oligosaccharides by hydrazinolysis from two lactoferrin samples of different races. 7068558 0 26 theme chains 30:35 arg1 study 11:15 Structural study 0:15 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 0:124 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 4 27 theme racial 699:704 arg1 difference 706:715 no racial difference 696:715 no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin 696:785 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 0 28 theme sugar 24:28 arg1 chains 30:35 the sugar chains 20:35 the sugar chains of human lactoferrin 20:56 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 4 29 theme sequential 567:576 arg1 digestion 593:601 sequential exoglycosidase digestion 567:601 sequential exoglycosidase digestion in combination with methylation analysis 567:642 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 3 30 theme column 442:447 arg1 chromatography 449:462 Bio-Gel P-4 column chromatography 430:462 Bio-Gel P-4 column chromatography 430:462 The two oligosaccharide fractions gave exactly the same fractionation pattern upon paper electrophoresis and Bio-Gel P-4 column chromatography after sialidase digestion. 7068558 0 31 theme human 40:44 arg1 lactoferrin 46:56 human lactoferrin 40:56 human lactoferrin 40:56 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 3 32 theme same 372:375 arg1 pattern 391:397 exactly the same fractionation pattern 360:397 exactly the same fractionation pattern 360:397 The two oligosaccharide fractions gave exactly the same fractionation pattern upon paper electrophoresis and Bio-Gel P-4 column chromatography after sialidase digestion. 7068558 3 33 theme sialidase 470:478 arg1 digestion 480:488 sialidase digestion 470:488 sialidase digestion 470:488 The two oligosaccharide fractions gave exactly the same fractionation pattern upon paper electrophoresis and Bio-Gel P-4 column chromatography after sialidase digestion. 7068558 4 34 theme chain 759:763 arg1 moiety 765:770 the sugar chain moiety 749:770 the sugar chain moiety of lactoferrin 749:785 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 3 35 theme Bio-Gel 430:436 arg1 chromatography 449:462 Bio-Gel P-4 column chromatography 430:462 Bio-Gel P-4 column chromatography 430:462 The two oligosaccharide fractions gave exactly the same fractionation pattern upon paper electrophoresis and Bio-Gel P-4 column chromatography after sialidase digestion. 7068558 2 36 theme sugar 207:211 arg1 chains 213:218 These sugar chains 201:218 These sugar chains 201:218 These sugar chains were released as oligosaccharides by hydrazinolysis from two lactoferrin samples of different races. 7068558 2 36 theme sugar 207:211 arg1 oligosaccharides 237:252 oligosaccharides 237:252 oligosaccharides 237:252 These sugar chains were released as oligosaccharides by hydrazinolysis from two lactoferrin samples of different races. 7068558 4 37 theme sugar 753:757 arg1 moiety 765:770 the sugar chain moiety 749:770 the sugar chain moiety of lactoferrin 749:785 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 4 38 theme exoglycosidase 578:591 arg1 digestion 593:601 sequential exoglycosidase digestion 567:601 sequential exoglycosidase digestion in combination with methylation analysis 567:642 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 4 39 dep quality 725:731 arg1 both 717:720 both 717:720 both 717:720 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 0 40 link asparagine-linked 94:110 arg1 chains 118:123 four novel complex-type asparagine-linked sugar chains 70:123 four novel complex-type asparagine-linked sugar chains 70:123 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 1 41 theme Human 126:130 arg1 lactoferrin 132:142 Human lactoferrin 126:142 Human lactoferrin 126:142 Human lactoferrin contains 2 asparagine-linked sugar chains in 1 molecule. 7068558 4 42 theme same 658:661 arg1 results 663:669 the same results 654:669 the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin 654:785 A structural study of the oligosaccharides obtained from the two samples by sequential exoglycosidase digestion in combination with methylation analysis also gave the same results indicating that there is no racial difference both in quality and quantity of the sugar chain moiety of lactoferrin. 7068558 0 43 dep study 11:15 arg1 finding 59:65 finding 59:65 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 0:124 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 7068558 0 44 theme lactoferrin 46:56 arg1 chains 30:35 the sugar chains 20:35 the sugar chains of human lactoferrin 20:56 Structural study of the sugar chains of human lactoferrin: finding of four novel complex-type asparagine-linked sugar chains. 32125861 0 0 theme Single 80:85 arg1 Donor 87:91 a Single Donor 78:91 a Single Donor 78:91 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 2 1 theme human 497:501 arg1 N-glycoproteome 508:522 the human milk N-glycoproteome 493:522 the human milk N-glycoproteome 493:522 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 5 2 gly glycoproteins 1104:1116 arg1 glycoproteins 1104:1116 50 glycoproteins 1101:1116 50 glycoproteins 1101:1116 We next quantified 287 of these glycopeptides originating from 50 glycoproteins using a targeted proteomics approach. 32125861 1 3 gly N-glycosylation 175:189 arg1 proteins 205:212 human milk proteins 194:212 human milk proteins 194:212 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 1 4 theme Protein 167:173 arg1 N-glycosylation 175:189 Protein N-glycosylation 167:189 Protein N-glycosylation on human milk proteins 167:212 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 8 5 theme observed 1532:1539 arg1 microheterogeneity 1555:1572 the observed glycosylation microheterogeneity 1528:1572 the observed glycosylation microheterogeneity 1528:1572 Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants. 32125861 3 6 theme proteome-wide 759:771 arg1 monitoring 773:782 the proteome-wide monitoring 755:782 the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein 755:861 Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein. 32125861 3 7 theme breast 843:848 arg1 protein 855:861 breast milk protein 843:861 breast milk protein 843:861 Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein. 32125861 8 8 theme glycoproteomics 1424:1438 arg1 approach 1440:1447 the improved glycoproteomics approach 1411:1447 the improved glycoproteomics approach outlined above 1411:1462 Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants. 32125861 8 9 theme future 1465:1470 arg1 studies 1472:1478 future studies 1465:1478 future studies 1465:1478 Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants. 32125861 2 10 theme personalized 546:557 arg1 approaches 559:568 longitudinal personalized approaches 533:568 longitudinal personalized approaches 533:568 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 6 11 gly glycoprotein 1170:1181 arg1 glycoprotein 1170:1181 each glycoprotein 1165:1181 each glycoprotein 1165:1181 Although each glycoprotein, N-glycosylation site, and attached glycan revealed distinct dynamic changes, we did observe a few general trends. 32125861 8 12 theme improved 1415:1422 arg1 approach 1440:1447 the improved glycoproteomics approach 1411:1447 the improved glycoproteomics approach outlined above 1411:1462 Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants. 32125861 2 13 theme longitudinal 533:544 arg1 approaches 559:568 longitudinal personalized approaches 533:568 longitudinal personalized approaches 533:568 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 4 14 gly glycoproteins 919:931 arg1 glycoproteins 919:931 110 glycoproteins 915:931 110 glycoproteins covering 191 glycosites 915:955 We were able to map around 1700 glycopeptides from 110 glycoproteins covering 191 glycosites, of which 43 sites have not been previously reported with experimental evidence. 32125861 8 15 theme healthy 1581:1587 arg1 development 1589:1599 the healthy development 1577:1599 the healthy development of infants 1577:1610 Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants. 32125861 0 16 from N-Glycoproteome 43:57 arg1 Donor 87:91 a Single Donor 78:91 a Single Donor 78:91 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 5 17 gly glycopeptides 1070:1082 arg2 glycopeptides 1070:1082 these glycopeptides 1064:1082 these glycopeptides originating from 50 glycoproteins 1064:1116 We next quantified 287 of these glycopeptides originating from 50 glycoproteins using a targeted proteomics approach. 32125861 2 18 theme milk 400:403 arg1 uniqueness 372:381 the individual uniqueness 357:381 the individual uniqueness of each mother's milk 357:403 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 2 18 theme milk 400:403 arg1 complexity 421:430 the overall complexity 409:430 the overall complexity 409:430 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 2 18 theme milk 400:403 arg1 changes 445:451 temporal changes 436:451 temporal changes 436:451 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 2 19 theme protein 456:462 arg1 N-glycosylation 464:478 protein N-glycosylation 456:478 protein N-glycosylation 456:478 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 3 20 theme N-glycopeptides 794:808 arg1 monitoring 773:782 the proteome-wide monitoring 755:782 the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein 755:861 Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein. 32125861 6 21 theme dynamic 1244:1250 arg1 changes 1252:1258 distinct dynamic changes 1235:1258 distinct dynamic changes 1235:1258 Although each glycoprotein, N-glycosylation site, and attached glycan revealed distinct dynamic changes, we did observe a few general trends. 32125861 1 22 theme human 194:198 arg1 proteins 205:212 human milk proteins 194:212 human milk proteins 194:212 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 0 23 theme Quantitative 0:11 arg1 Inventory 26:34 Quantitative Longitudinal Inventory 0:34 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor 0:91 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 5 24 theme targeted 1126:1133 arg1 approach 1146:1153 a targeted proteomics approach 1124:1153 a targeted proteomics approach 1124:1153 We next quantified 287 of these glycopeptides originating from 50 glycoproteins using a targeted proteomics approach. 32125861 3 25 theme -based 728:733 arg1 cartridges 735:744 hydrophilic-interaction chromatography (HILIC)-based cartridges 682:744 hydrophilic-interaction chromatography (HILIC)-based cartridges 682:744 Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein. 32125861 6 26 theme distinct 1235:1242 arg1 changes 1252:1258 distinct dynamic changes 1235:1258 distinct dynamic changes 1235:1258 Although each glycoprotein, N-glycosylation site, and attached glycan revealed distinct dynamic changes, we did observe a few general trends. 32125861 1 27 theme milk 200:203 arg1 proteins 205:212 human milk proteins 194:212 human milk proteins 194:212 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 1 28 theme competitive 285:295 arg1 inhibitors 297:306 competitive inhibitors 285:306 competitive inhibitors of pathogen binding and immunomodulators 285:347 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 1 28 theme competitive 285:295 arg1 functions 259:267 functions 259:267 functions 259:267 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 1 28 theme competitive 285:295 arg1 health 248:253 an infant's health 236:253 an infant's health 236:253 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 8 29 theme glycosylation 1541:1553 arg1 microheterogeneity 1555:1572 the observed glycosylation microheterogeneity 1528:1572 the observed glycosylation microheterogeneity 1528:1572 Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants. 32125861 8 30 from impact 1518:1523 arg1 development 1589:1599 the healthy development 1577:1599 the healthy development of infants 1577:1610 Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants. 32125861 7 31 theme lactation 1381:1389 arg1 period 1391:1396 the lactation period 1377:1396 the lactation period 1377:1396 For instance, fucosylation, especially terminal fucosylation, increased across the lactation period. 32125861 2 32 theme temporal 436:443 arg1 changes 445:451 temporal changes 436:451 temporal changes 436:451 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 3 33 gly N-glycopeptides 794:808 arg2 N-glycopeptides 794:808 intact N-glycopeptides 787:808 intact N-glycopeptides using just a digest of 150 μg of breast milk protein 787:861 Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein. 32125861 0 34 theme Variable 112:119 arg1 Repertoire 121:130 the Highly Variable Repertoire 101:130 the Highly Variable Repertoire 101:130 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 5 35 theme proteomics 1135:1144 arg1 approach 1146:1153 a targeted proteomics approach 1124:1153 a targeted proteomics approach 1124:1153 We next quantified 287 of these glycopeptides originating from 50 glycoproteins using a targeted proteomics approach. 32125861 2 36 theme individual 361:370 arg1 uniqueness 372:381 the individual uniqueness 357:381 the individual uniqueness of each mother's milk 357:403 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 4 37 gly glycopeptides 896:908 arg1 glycoproteins 919:931 110 glycoproteins 915:931 110 glycoproteins covering 191 glycosites 915:955 We were able to map around 1700 glycopeptides from 110 glycoproteins covering 191 glycosites, of which 43 sites have not been previously reported with experimental evidence. 32125861 4 37 gly glycopeptides 896:908 arg2 glycopeptides 896:908 1700 glycopeptides 891:908 1700 glycopeptides 891:908 We were able to map around 1700 glycopeptides from 110 glycoproteins covering 191 glycosites, of which 43 sites have not been previously reported with experimental evidence. 32125861 0 38 theme N-Glycoproteome 43:57 arg1 Inventory 26:34 Quantitative Longitudinal Inventory 0:34 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor 0:91 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 0 39 theme Dynamic 136:142 arg1 Changes 158:164 Dynamic Site-Specific Changes 136:164 Dynamic Site-Specific Changes 136:164 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 5 40 theme glycopeptides 1070:1082 arg1 287 1057:1059 287 1057:1059 287 of these glycopeptides originating from 50 glycoproteins 1057:1116 We next quantified 287 of these glycopeptides originating from 50 glycoproteins using a targeted proteomics approach. 32125861 4 41 gly glycosites 946:955 arg2 glycosites 946:955 191 glycosites 942:955 191 glycosites 942:955 We were able to map around 1700 glycopeptides from 110 glycoproteins covering 191 glycosites, of which 43 sites have not been previously reported with experimental evidence. 32125861 2 42 theme overall 413:419 arg1 complexity 421:430 the overall complexity 409:430 the overall complexity 409:430 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 1 43 theme pathogen 311:318 arg1 binding 320:326 pathogen binding 311:326 pathogen binding 311:326 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 8 44 theme microheterogeneity 1555:1572 arg1 impact 1518:1523 the potential impact 1504:1523 the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants 1504:1610 Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants. 32125861 0 45 theme Human 62:66 arg1 Milk 68:71 Human Milk 62:71 Human Milk from a Single Donor 62:91 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 1 46 theme binding 320:326 arg1 inhibitors 297:306 competitive inhibitors 285:306 competitive inhibitors of pathogen binding and immunomodulators 285:347 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 1 46 theme binding 320:326 arg1 functions 259:267 functions 259:267 functions 259:267 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 1 46 theme binding 320:326 arg1 health 248:253 an infant's health 236:253 an infant's health 236:253 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 0 47 theme Milk 68:71 arg1 N-Glycoproteome 43:57 the N-Glycoproteome 39:57 the N-Glycoproteome of Human Milk from a Single Donor 39:91 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 3 48 theme intact 787:792 arg1 N-glycopeptides 794:808 intact N-glycopeptides 787:808 intact N-glycopeptides using just a digest of 150 μg of breast milk protein 787:861 Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein. 32125861 6 49 theme attached 1210:1217 arg1 glycan 1219:1224 attached glycan 1210:1224 attached glycan 1210:1224 Although each glycoprotein, N-glycosylation site, and attached glycan revealed distinct dynamic changes, we did observe a few general trends. 32125861 2 50 theme N-glycosylation 464:478 arg1 uniqueness 372:381 the individual uniqueness 357:381 the individual uniqueness of each mother's milk 357:403 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 2 50 theme N-glycosylation 464:478 arg1 complexity 421:430 the overall complexity 409:430 the overall complexity 409:430 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 2 50 theme N-glycosylation 464:478 arg1 changes 445:451 temporal changes 436:451 temporal changes 436:451 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 3 51 theme μg 837:838 arg1 digest 823:828 a digest 821:828 a digest of 150 μg of breast milk protein 821:861 Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein. 32125861 0 52 theme Site-Specific 144:156 arg1 Changes 158:164 Dynamic Site-Specific Changes 136:164 Dynamic Site-Specific Changes 136:164 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 4 53 theme experimental 1015:1026 arg1 evidence 1028:1035 experimental evidence 1015:1035 experimental evidence 1015:1035 We were able to map around 1700 glycopeptides from 110 glycoproteins covering 191 glycosites, of which 43 sites have not been previously reported with experimental evidence. 32125861 1 54 theme immunomodulators 332:347 arg1 inhibitors 297:306 competitive inhibitors 285:306 competitive inhibitors of pathogen binding and immunomodulators 285:347 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 1 54 theme immunomodulators 332:347 arg1 functions 259:267 functions 259:267 functions 259:267 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 1 54 theme immunomodulators 332:347 arg1 health 248:253 an infant's health 236:253 an infant's health 236:253 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 2 55 theme quantitative 610:621 arg1 information 623:633 N-site-specific quantitative information 594:633 N-site-specific quantitative information 594:633 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 8 56 theme potential 1508:1516 arg1 impact 1518:1523 the potential impact 1504:1523 the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants 1504:1610 Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants. 32125861 6 57 theme general 1282:1288 arg1 trends 1290:1295 a few general trends 1276:1295 a few general trends 1276:1295 Although each glycoprotein, N-glycosylation site, and attached glycan revealed distinct dynamic changes, we did observe a few general trends. 32125861 6 58 gly N-glycosylation 1184:1198 arg2 site 1200:1203 N-glycosylation site 1184:1203 N-glycosylation site 1184:1203 Although each glycoprotein, N-glycosylation site, and attached glycan revealed distinct dynamic changes, we did observe a few general trends. 32125861 7 59 theme terminal 1337:1344 arg1 fucosylation 1346:1357 terminal fucosylation 1337:1357 especially terminal fucosylation 1326:1357 For instance, fucosylation, especially terminal fucosylation, increased across the lactation period. 32125861 7 59 theme terminal 1337:1344 arg1 fucosylation 1312:1323 fucosylation 1312:1323 fucosylation 1312:1323 For instance, fucosylation, especially terminal fucosylation, increased across the lactation period. 32125861 2 60 theme N-site-specific 594:608 arg1 information 623:633 N-site-specific quantitative information 594:633 N-site-specific quantitative information 594:633 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 6 61 theme few 1278:1280 arg1 trends 1290:1295 a few general trends 1276:1295 a few general trends 1276:1295 Although each glycoprotein, N-glycosylation site, and attached glycan revealed distinct dynamic changes, we did observe a few general trends. 32125861 2 62 theme N-glycoproteome 508:522 arg1 analysis 481:488 analysis 481:488 analysis of the human milk N-glycoproteome 481:522 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 0 63 from Donor 87:91 arg1 N-Glycoproteome 43:57 the N-Glycoproteome 39:57 the N-Glycoproteome of Human Milk from a Single Donor 39:91 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 0 63 from Donor 87:91 arg1 Milk 68:71 Human Milk 62:71 Human Milk from a Single Donor 62:91 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 4 64 from glycoproteins 919:931 arg1 glycopeptides 896:908 1700 glycopeptides 891:908 1700 glycopeptides 891:908 We were able to map around 1700 glycopeptides from 110 glycoproteins covering 191 glycosites, of which 43 sites have not been previously reported with experimental evidence. 32125861 6 65 theme N-glycosylation 1184:1198 arg1 site 1200:1203 N-glycosylation site 1184:1203 N-glycosylation site 1184:1203 Although each glycoprotein, N-glycosylation site, and attached glycan revealed distinct dynamic changes, we did observe a few general trends. 32125861 3 66 theme protein 855:861 arg1 μg 837:838 150 μg 833:838 150 μg of breast milk protein 833:861 Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein. 32125861 2 67 theme milk 503:506 arg1 N-glycoproteome 508:522 the human milk N-glycoproteome 493:522 the human milk N-glycoproteome 493:522 Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. 32125861 8 68 theme infants 1604:1610 arg1 development 1589:1599 the healthy development 1577:1599 the healthy development of infants 1577:1610 Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants. 32125861 3 69 theme automated 657:665 arg1 platform 667:674 an automated platform 654:674 an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges 654:744 Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein. 32125861 1 70 from N-glycosylation 175:189 arg1 proteins 205:212 human milk proteins 194:212 human milk proteins 194:212 Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. 32125861 0 71 theme Longitudinal 13:24 arg1 Inventory 26:34 Quantitative Longitudinal Inventory 0:34 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor 0:91 Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes. 32125861 3 72 theme milk 850:853 arg1 protein 855:861 breast milk protein 843:861 breast milk protein 843:861 Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 μg of breast milk protein. 7372597 3 0 theme shortest 363:370 arg1 oligosaccharides 380:395 The shortest neutral oligosaccharides 359:395 The shortest neutral oligosaccharides 359:395 The shortest neutral oligosaccharides were subsequently fractionated by DAX4 anion exchange chromatography into 12 fractions. 7372597 6 1 dep galactose 788:796 arg1 beta 804:807 beta 1 804:809 galactose (Gal) beta 1 788:809 Two oligosaccharides and three trisaccharides were characterized as galactose (Gal) beta 1 leads to 3 N-acetylgalactosaminitol (GalNActitol), N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 leads to 3 GalNActitol, GlcNAc 1 leads to 3 Gal 1 leads to 3 GalNActitol and fucose alpha 1 leads to 2 Gal beta 1 leads to 3 GalNActitol. 7372597 3 2 theme neutral 372:378 arg1 oligosaccharides 380:395 The shortest neutral oligosaccharides 359:395 The shortest neutral oligosaccharides 359:395 The shortest neutral oligosaccharides were subsequently fractionated by DAX4 anion exchange chromatography into 12 fractions. 7372597 4 3 theme preparative 530:540 arg1 chromatography 548:561 preparative paper chromatography 530:561 preparative paper chromatography 530:561 Five major oligosaccharides were purified by preparative paper chromatography. 7372597 2 4 theme glycopeptides 331:343 arg1 mixture 291:297 a heterogeneous mixture 275:297 a heterogeneous mixture of reduced oligosaccharides and glycopeptides 275:343 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 3 5 theme DAX4 431:434 arg1 chromatography 451:464 DAX4 anion exchange chromatography 431:464 DAX4 anion exchange chromatography 431:464 The shortest neutral oligosaccharides were subsequently fractionated by DAX4 anion exchange chromatography into 12 fractions. 7372597 6 6 theme GlcNAc 883:888 arg1 beta 891:894 N-acetylglucosamine (GlcNAc) beta 1 862:896 N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 862:946 Two oligosaccharides and three trisaccharides were characterized as galactose (Gal) beta 1 leads to 3 N-acetylgalactosaminitol (GalNActitol), N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 leads to 3 GalNActitol, GlcNAc 1 leads to 3 Gal 1 leads to 3 GalNActitol and fucose alpha 1 leads to 2 Gal beta 1 leads to 3 GalNActitol. 7372597 5 7 theme periodic 606:613 arg1 oxidation 615:623 periodic oxidation 606:623 periodic oxidation 606:623 Their structures were determined by using periodic oxidation, methylation analysis, gas liquid chromatography-mass spectrometry, and enzymatic degradation. 7372597 2 8 theme oligosaccharides 310:325 arg1 mixture 291:297 a heterogeneous mixture 275:297 a heterogeneous mixture of reduced oligosaccharides and glycopeptides 275:343 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 6 9 dep beta 891:894 arg1 leads 898:902 leads 898:902 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 898:946 Two oligosaccharides and three trisaccharides were characterized as galactose (Gal) beta 1 leads to 3 N-acetylgalactosaminitol (GalNActitol), N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 leads to 3 GalNActitol, GlcNAc 1 leads to 3 Gal 1 leads to 3 GalNActitol and fucose alpha 1 leads to 2 Gal beta 1 leads to 3 GalNActitol. 7372597 2 10 theme reduced 302:308 arg1 oligosaccharides 310:325 reduced oligosaccharides 302:325 reduced oligosaccharides 302:325 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 2 11 theme bronchial 147:155 arg1 glycoproteins 157:169 Human bronchial glycoproteins 141:169 Human bronchial glycoproteins from a patient suffering from chronic bronchitis 141:218 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 2 12 gly glycoproteins 157:169 arg1 glycoproteins 157:169 Human bronchial glycoproteins 141:169 Human bronchial glycoproteins from a patient suffering from chronic bronchitis 141:218 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 6 13 theme fucose 1025:1030 arg1 alpha 1032:1036 fucose alpha 1 1025:1038 fucose alpha 1 1025:1038 Two oligosaccharides and three trisaccharides were characterized as galactose (Gal) beta 1 leads to 3 N-acetylgalactosaminitol (GalNActitol), N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 leads to 3 GalNActitol, GlcNAc 1 leads to 3 Gal 1 leads to 3 GalNActitol and fucose alpha 1 leads to 2 Gal beta 1 leads to 3 GalNActitol. 7372597 3 14 theme anion 436:440 arg1 chromatography 451:464 DAX4 anion exchange chromatography 431:464 DAX4 anion exchange chromatography 431:464 The shortest neutral oligosaccharides were subsequently fractionated by DAX4 anion exchange chromatography into 12 fractions. 7372597 5 15 theme enzymatic 697:705 arg1 degradation 707:717 enzymatic degradation 697:717 enzymatic degradation 697:717 Their structures were determined by using periodic oxidation, methylation analysis, gas liquid chromatography-mass spectrometry, and enzymatic degradation. 7372597 3 16 theme exchange 442:449 arg1 chromatography 451:464 DAX4 anion exchange chromatography 431:464 DAX4 anion exchange chromatography 431:464 The shortest neutral oligosaccharides were subsequently fractionated by DAX4 anion exchange chromatography into 12 fractions. 7372597 2 17 theme chronic 201:207 arg1 bronchitis 209:218 chronic bronchitis 201:218 chronic bronchitis 201:218 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 6 18 dep Gal 922:924 arg1 leads 928:932 leads 928:932 leads to 4 GlcNAc 1 928:946 Two oligosaccharides and three trisaccharides were characterized as galactose (Gal) beta 1 leads to 3 N-acetylgalactosaminitol (GalNActitol), N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 leads to 3 GalNActitol, GlcNAc 1 leads to 3 Gal 1 leads to 3 GalNActitol and fucose alpha 1 leads to 2 Gal beta 1 leads to 3 GalNActitol. 7372597 6 19 dep beta 1055:1058 arg1 leads 1062:1066 leads 1062:1066 leads to 3 GalNActitol 1062:1083 Two oligosaccharides and three trisaccharides were characterized as galactose (Gal) beta 1 leads to 3 N-acetylgalactosaminitol (GalNActitol), N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 leads to 3 GalNActitol, GlcNAc 1 leads to 3 Gal 1 leads to 3 GalNActitol and fucose alpha 1 leads to 2 Gal beta 1 leads to 3 GalNActitol. 7372597 6 20 dep Gal 992:994 arg1 leads 998:1002 leads 998:1002 leads to 3 GalNActitol 998:1019 Two oligosaccharides and three trisaccharides were characterized as galactose (Gal) beta 1 leads to 3 N-acetylgalactosaminitol (GalNActitol), N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 leads to 3 GalNActitol, GlcNAc 1 leads to 3 Gal 1 leads to 3 GalNActitol and fucose alpha 1 leads to 2 Gal beta 1 leads to 3 GalNActitol. 7372597 0 21 theme glycoproteins 36:48 arg1 Oligosaccharides 0:15 Oligosaccharides 0:15 Oligosaccharides of human bronchial glycoproteins 0:48 Oligosaccharides of human bronchial glycoproteins. 7372597 0 22 theme bronchial 26:34 arg1 glycoproteins 36:48 human bronchial glycoproteins 20:48 human bronchial glycoproteins 20:48 Oligosaccharides of human bronchial glycoproteins. 7372597 4 23 theme paper 542:546 arg1 chromatography 548:561 preparative paper chromatography 530:561 preparative paper chromatography 530:561 Five major oligosaccharides were purified by preparative paper chromatography. 7372597 2 24 theme borohydride 247:257 arg1 degradation 259:269 alkaline borohydride degradation 238:269 alkaline borohydride degradation 238:269 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 5 25 theme gas 648:650 arg1 spectrometry 679:690 gas liquid chromatography-mass spectrometry 648:690 gas liquid chromatography-mass spectrometry 648:690 Their structures were determined by using periodic oxidation, methylation analysis, gas liquid chromatography-mass spectrometry, and enzymatic degradation. 7372597 1 26 theme chronic 121:127 arg1 bronchitis 129:138 chronic bronchitis 121:138 chronic bronchitis 121:138 Neutral di- and trisaccharides isolated from a patient suffering from chronic bronchitis. 7372597 2 27 theme alkaline 238:245 arg1 degradation 259:269 alkaline borohydride degradation 238:269 alkaline borohydride degradation 238:269 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 5 28 theme liquid 652:657 arg1 spectrometry 679:690 gas liquid chromatography-mass spectrometry 648:690 gas liquid chromatography-mass spectrometry 648:690 Their structures were determined by using periodic oxidation, methylation analysis, gas liquid chromatography-mass spectrometry, and enzymatic degradation. 7372597 4 29 theme major 490:494 arg1 oligosaccharides 496:511 Five major oligosaccharides 485:511 Five major oligosaccharides 485:511 Five major oligosaccharides were purified by preparative paper chromatography. 7372597 0 30 gly glycoproteins 36:48 arg1 glycoproteins 36:48 human bronchial glycoproteins 20:48 human bronchial glycoproteins 20:48 Oligosaccharides of human bronchial glycoproteins. 7372597 5 31 theme chromatography-mass 659:677 arg1 spectrometry 679:690 gas liquid chromatography-mass spectrometry 648:690 gas liquid chromatography-mass spectrometry 648:690 Their structures were determined by using periodic oxidation, methylation analysis, gas liquid chromatography-mass spectrometry, and enzymatic degradation. 7372597 6 32 theme N-acetylglucosamine 862:880 arg1 beta 891:894 N-acetylglucosamine (GlcNAc) beta 1 862:896 N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 862:946 Two oligosaccharides and three trisaccharides were characterized as galactose (Gal) beta 1 leads to 3 N-acetylgalactosaminitol (GalNActitol), N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 leads to 3 GalNActitol, GlcNAc 1 leads to 3 Gal 1 leads to 3 GalNActitol and fucose alpha 1 leads to 2 Gal beta 1 leads to 3 GalNActitol. 7372597 2 33 theme heterogeneous 277:289 arg1 mixture 291:297 a heterogeneous mixture 275:297 a heterogeneous mixture of reduced oligosaccharides and glycopeptides 275:343 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 6 34 theme Gal 1051:1053 arg1 beta 1055:1058 2 Gal beta 1 1049:1060 2 Gal beta 1 leads to 3 GalNActitol 1049:1083 Two oligosaccharides and three trisaccharides were characterized as galactose (Gal) beta 1 leads to 3 N-acetylgalactosaminitol (GalNActitol), N-acetylglucosamine (GlcNAc) beta 1 leads to 3 GalNActitol, Gal 1 leads to 4 GlcNAc 1 leads to 3 GalNActitol, GlcNAc 1 leads to 3 Gal 1 leads to 3 GalNActitol and fucose alpha 1 leads to 2 Gal beta 1 leads to 3 GalNActitol. 7372597 2 35 from patient 178:184 arg1 glycoproteins 157:169 Human bronchial glycoproteins 141:169 Human bronchial glycoproteins from a patient suffering from chronic bronchitis 141:218 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 2 36 theme Human 141:145 arg1 glycoproteins 157:169 Human bronchial glycoproteins 141:169 Human bronchial glycoproteins from a patient suffering from chronic bronchitis 141:218 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 7372597 0 37 theme human 20:24 arg1 glycoproteins 36:48 human bronchial glycoproteins 20:48 human bronchial glycoproteins 20:48 Oligosaccharides of human bronchial glycoproteins. 7372597 5 38 theme methylation 626:636 arg1 analysis 638:645 methylation analysis 626:645 methylation analysis 626:645 Their structures were determined by using periodic oxidation, methylation analysis, gas liquid chromatography-mass spectrometry, and enzymatic degradation. 7372597 2 39 gly glycopeptides 331:343 arg2 glycopeptides 331:343 glycopeptides 331:343 glycopeptides 331:343 Human bronchial glycoproteins from a patient suffering from chronic bronchitis were subjected to alkaline borohydride degradation and a heterogeneous mixture of reduced oligosaccharides and glycopeptides was obtained. 2136351 3 0 theme major 993:997 arg1 Gal 988:990 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta 954:1013 Gal 988:990 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 0 theme major 993:997 arg1 1-6 1015:1017 1-6 1015:1017 1-6 1015:1017 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 1 1 theme high-molecular 156:169 arg1 glycopeptides 178:190 mucin-derived high-molecular weight glycopeptides 142:190 mucin-derived high-molecular weight glycopeptides 142:190 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 3 2 from species 605:611 arg1 fraction 627:634 the acidic fraction 616:634 the acidic fraction 616:634 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 2 3 theme spectroscopy 543:554 arg1 combination 424:434 a combination 422:434 a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy 422:554 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 3 4 with type 914:917 arg1 preponderance 937:949 a particular preponderance 924:949 a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor) 924:1035 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 1 5 gly glycopeptides 178:190 arg2 glycopeptides 178:190 mucin-derived high-molecular weight glycopeptides 142:190 mucin-derived high-molecular weight glycopeptides 142:190 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 0 6 link O-linked 21:28 arg1 polylactosaminoglycans 30:51 acidic O-linked polylactosaminoglycans 14:51 acidic O-linked polylactosaminoglycans 14:51 Structures of acidic O-linked polylactosaminoglycans on human skim milk mucins. 2136351 1 7 theme weight 171:176 arg1 glycopeptides 178:190 mucin-derived high-molecular weight glycopeptides 142:190 mucin-derived high-molecular weight glycopeptides 142:190 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 3 8 dep units 1023:1027 arg1 minor 1030:1034 minor 1030:1034 minor 1030:1034 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 0 9 from Structures 0:9 arg1 mucins 72:77 human skim milk mucins 56:77 human skim milk mucins 56:77 Structures of acidic O-linked polylactosaminoglycans on human skim milk mucins. 2136351 3 10 theme Gal 1019:1021 arg1 units 1023:1027 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units 954:1027 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor) 954:1035 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 1 11 dep milk 127:130 arg1 mucins 132:137 mucins 132:137 mucins 132:137 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 3 12 theme poly-N-acetyllactosamine 889:912 arg1 type 914:917 the poly-N-acetyllactosamine type 885:917 the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor) 885:1035 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 13 theme GlcNAc 1003:1008 arg1 beta 1010:1013 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta 954:1013 beta 1010:1013 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 2 14 theme acidic 316:321 arg1 fraction 323:330 the acidic fraction 312:330 the acidic fraction 312:330 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 3 15 from mucins 728:733 arg1 oligosaccharides 690:705 the neutral oligosaccharides 678:705 the neutral oligosaccharides from human skim milk mucins 678:733 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 2 16 theme spectrometry 466:477 arg1 combination 424:434 a combination 422:434 a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy 422:554 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 3 17 theme major 599:603 arg1 species 605:611 these major species 593:611 these major species in the acidic fraction 593:634 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 2 18 theme atom 444:447 arg1 spectrometry 466:477 fast atom bombardment mass spectrometry 439:477 fast atom bombardment mass spectrometry 439:477 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 2 19 theme MHz 509:511 arg1 resonance 533:541 500 MHz 1H-nuclear magnetic resonance 505:541 500 MHz 1H-nuclear magnetic resonance spectroscopy 505:554 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 3 20 theme units 1023:1027 arg1 preponderance 937:949 a particular preponderance 924:949 a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor) 924:1035 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 1 21 theme O-Linked 80:87 arg1 glycans 89:95 O-Linked glycans 80:95 O-Linked glycans 80:95 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 3 22 dep type 844:847 arg1 2 801:801 2 801:801 2 801:801 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 2 23 theme fast 439:442 arg1 spectrometry 466:477 fast atom bombardment mass spectrometry 439:477 fast atom bombardment mass spectrometry 439:477 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 2 24 theme magnetic 524:531 arg1 resonance 533:541 500 MHz 1H-nuclear magnetic resonance 505:541 500 MHz 1H-nuclear magnetic resonance spectroscopy 505:554 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 2 25 theme high 349:352 arg1 chromatography 373:386 high performance liquid chromatography 349:386 high performance liquid chromatography 349:386 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 3 26 theme particular 926:935 arg1 preponderance 937:949 a particular preponderance 924:949 a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor) 924:1035 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 27 dep type 914:917 arg1 3 852:852 3 852:852 3 852:852 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 28 theme GlcNAc 972:977 arg1 Gal 988:990 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta 954:1013 Gal 988:990 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 28 theme GlcNAc 972:977 arg1 1-6 1015:1017 1-6 1015:1017 1-6 1015:1017 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 0 29 theme O-linked 21:28 arg1 polylactosaminoglycans 30:51 acidic O-linked polylactosaminoglycans 14:51 acidic O-linked polylactosaminoglycans 14:51 Structures of acidic O-linked polylactosaminoglycans on human skim milk mucins. 2136351 3 30 theme neutral 682:688 arg1 oligosaccharides 690:705 the neutral oligosaccharides 678:705 the neutral oligosaccharides from human skim milk mucins 678:733 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 31 theme beta 1010:1013 arg1 units 1023:1027 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units 954:1027 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor) 954:1035 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 32 theme acidic 620:625 arg1 fraction 627:634 the acidic fraction 616:634 the acidic fraction 616:634 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 33 theme beta 979:982 arg1 Gal 988:990 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta 954:1013 Gal 988:990 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 33 theme beta 979:982 arg1 1-6 1015:1017 1-6 1015:1017 1-6 1015:1017 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 1 34 theme anion 212:216 arg1 chromatography 227:240 anion exchange chromatography 212:240 anion exchange chromatography into neutral and acidic alditols 212:273 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 0 35 theme acidic 14:19 arg1 polylactosaminoglycans 30:51 acidic O-linked polylactosaminoglycans 14:51 acidic O-linked polylactosaminoglycans 14:51 Structures of acidic O-linked polylactosaminoglycans on human skim milk mucins. 2136351 2 36 theme 1H-nuclear 513:522 arg1 resonance 533:541 500 MHz 1H-nuclear magnetic resonance 505:541 500 MHz 1H-nuclear magnetic resonance spectroscopy 505:554 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 1 37 theme exchange 218:225 arg1 chromatography 227:240 anion exchange chromatography 212:240 anion exchange chromatography into neutral and acidic alditols 212:273 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 2 38 theme resonance 533:541 arg1 spectroscopy 543:554 500 MHz 1H-nuclear magnetic resonance spectroscopy 505:554 500 MHz 1H-nuclear magnetic resonance spectroscopy 505:554 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 3 39 theme structural 561:570 arg1 aspects 572:578 The structural aspects 557:578 The structural aspects 557:578 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 40 theme extended 963:970 arg1 Gal 988:990 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta 954:1013 Gal 988:990 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 40 theme extended 963:970 arg1 1-6 1015:1017 1-6 1015:1017 1-6 1015:1017 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 2 41 theme mass 461:464 arg1 spectrometry 466:477 fast atom bombardment mass spectrometry 439:477 fast atom bombardment mass spectrometry 439:477 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 0 42 theme polylactosaminoglycans 30:51 arg1 Structures 0:9 Structures 0:9 Structures of acidic O-linked polylactosaminoglycans on human skim milk mucins. 0:78 Structures of acidic O-linked polylactosaminoglycans on human skim milk mucins. 2136351 1 43 link mucin-derived 142:154 arg1 glycopeptides 178:190 mucin-derived high-molecular weight glycopeptides 142:190 mucin-derived high-molecular weight glycopeptides 142:190 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 3 44 theme skim 718:721 arg1 mucins 728:733 human skim milk mucins 712:733 human skim milk mucins 712:733 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 2 45 theme analysis 492:499 arg1 combination 424:434 a combination 422:434 a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy 422:554 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 2 46 theme bombardment 449:459 arg1 spectrometry 466:477 fast atom bombardment mass spectrometry 439:477 fast atom bombardment mass spectrometry 439:477 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 0 47 theme skim 62:65 arg1 mucins 72:77 human skim milk mucins 56:77 human skim milk mucins 56:77 Structures of acidic O-linked polylactosaminoglycans on human skim milk mucins. 2136351 3 48 theme milk 723:726 arg1 mucins 728:733 human skim milk mucins 712:733 human skim milk mucins 712:733 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 49 theme Gal 988:990 arg1 units 1023:1027 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units 954:1027 linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor) 954:1035 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 1 50 theme human 116:120 arg1 milk 127:130 human skim milk mucins or mucin-derived high-molecular weight glycopeptides 116:190 milk 127:130 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 0 51 theme human 56:60 arg1 mucins 72:77 human skim milk mucins 56:77 human skim milk mucins 56:77 Structures of acidic O-linked polylactosaminoglycans on human skim milk mucins. 2136351 3 52 theme core 808:811 arg1 structure 813:821 the core structure 804:821 the core structure 804:821 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 53 dep resemble 636:643 arg1 1 736:736 1 736:736 1 736:736 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 3 53 dep resemble 636:643 arg1 those 645:649 those 645:649 those 645:649 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 1 54 theme skim 122:125 arg1 milk 127:130 human skim milk mucins or mucin-derived high-molecular weight glycopeptides 116:190 milk 127:130 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 1 55 attach isolated 102:109 arg1 milk 127:130 human skim milk mucins or mucin-derived high-molecular weight glycopeptides 116:190 milk 127:130 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 1 55 attach isolated 102:109 arg1 glycopeptides 178:190 mucin-derived high-molecular weight glycopeptides 142:190 mucin-derived high-molecular weight glycopeptides 142:190 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 1 55 attach isolated 102:109 arg2 glycans 89:95 O-Linked glycans 80:95 O-Linked glycans 80:95 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 2 56 theme liquid 366:371 arg1 chromatography 373:386 high performance liquid chromatography 349:386 high performance liquid chromatography 349:386 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 1 57 theme neutral 247:253 arg1 alditols 266:273 neutral and acidic alditols 247:273 neutral and acidic alditols 247:273 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 3 58 theme human 712:716 arg1 mucins 728:733 human skim milk mucins 712:733 human skim milk mucins 712:733 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 2 59 theme performance 354:364 arg1 chromatography 373:386 high performance liquid chromatography 349:386 high performance liquid chromatography 349:386 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 3 60 theme backbone 859:866 arg1 sequences 868:876 the backbone sequences 855:876 the backbone sequences 855:876 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 2 61 theme Major 276:280 arg1 oligosaccharides 282:297 Major oligosaccharides 276:297 Major oligosaccharides contained in the acidic fraction 276:330 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 1 62 theme acidic 259:264 arg1 alditols 266:273 neutral and acidic alditols 247:273 neutral and acidic alditols 247:273 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 0 63 theme milk 67:70 arg1 mucins 72:77 human skim milk mucins 56:77 human skim milk mucins 56:77 Structures of acidic O-linked polylactosaminoglycans on human skim milk mucins. 2136351 3 64 theme alditols 755:762 arg1 size 743:746 the size 739:746 the size of the alditols 739:762 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2136351 2 65 theme methylation 480:490 arg1 analysis 492:499 methylation analysis 480:499 methylation analysis 480:499 Major oligosaccharides contained in the acidic fraction were purified by high performance liquid chromatography and structurally characterized by a combination of fast atom bombardment mass spectrometry, methylation analysis and 500 MHz 1H-nuclear magnetic resonance spectroscopy. 2136351 1 66 theme mucin-derived 142:154 arg1 glycopeptides 178:190 mucin-derived high-molecular weight glycopeptides 142:190 mucin-derived high-molecular weight glycopeptides 142:190 O-Linked glycans were isolated from human skim milk mucins or mucin-derived high-molecular weight glycopeptides and fractionated by anion exchange chromatography into neutral and acidic alditols. 2136351 3 67 theme ubiquitous 833:842 arg1 type 844:847 the ubiquitous type 2 829:849 the ubiquitous type 2 829:849 The structural aspects exhibited by these major species in the acidic fraction resemble those established previously for the neutral oligosaccharides from human skim milk mucins: 1) the size of the alditols varies from tri- to decasaccharides, 2) the core structure is of the ubiquitous type 2, 3) the backbone sequences are of the poly-N-acetyllactosamine type with a particular preponderance of linearly extended GlcNAc beta(1-3)Gal (major) or GlcNAc beta(1-6)Gal units (minor). 2580706 0 0 theme glycoproteins 98:110 arg1 oligosaccharides 63:78 the O-glycosidically linked core-region oligosaccharides 23:78 the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens 23:144 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. 2580706 3 1 theme permeation 761:770 arg1 chromatography 772:785 gel permeation chromatography 757:785 gel permeation chromatography 757:785 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 3 2 from chromatography 829:842 arg1 octadecylsilyl 847:860 octadecylsilyl 847:860 octadecylsilyl 847:860 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 3 2 from chromatography 829:842 arg1 columns 883:889 aminopropylsilyl columns 866:889 aminopropylsilyl columns 866:889 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 4 3 theme electron 967:974 arg1 spectrometry 988:999 electron impact mass spectrometry 967:999 electron impact mass spectrometry 967:999 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 0 4 theme meconium 89:96 arg1 glycoproteins 98:110 human meconium glycoproteins 83:110 human meconium glycoproteins which express oncofoetal antigens 83:144 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. 2580706 2 5 theme fucose 625:630 arg1 residues 632:639 sialic acid and fucose residues 609:639 residues 632:639 The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. 2580706 1 6 theme 67 285:286 arg1 % 287:287 % 287:287 % 287:287 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 4 7 theme NMR 1074:1076 arg1 spectroscopy 1078:1089 500-MHz proton NMR spectroscopy 1059:1089 500-MHz proton NMR spectroscopy 1059:1089 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 1 8 theme affinity 370:377 arg1 chromatography 379:392 affinity chromatography 370:392 affinity chromatography 370:392 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 4 9 theme mass 983:986 arg1 spectrometry 988:999 electron impact mass spectrometry 967:999 electron impact mass spectrometry 967:999 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 5 10 from structures 1098:1107 arg1 order 1113:1117 order 1113:1117 order of abundance 1113:1130 Their structures, in order of abundance, were: (Formula: see text). 2580706 1 11 theme % 287:287 arg1 ethanol 297:303 67% aqueous ethanol 285:303 67% aqueous ethanol 285:303 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 4 12 theme proton 1067:1072 arg1 spectroscopy 1078:1089 500-MHz proton NMR spectroscopy 1059:1089 500-MHz proton NMR spectroscopy 1059:1089 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 3 13 theme Bio-Gel 790:796 arg1 P4 798:799 Bio-Gel P4 and high performance liquid chromatography 790:842 P4 798:799 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 4 14 theme impact 976:981 arg1 spectrometry 988:999 electron impact mass spectrometry 967:999 electron impact mass spectrometry 967:999 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 5 15 dep see 1149:1151 arg1 Formula 1140:1146 Formula 1140:1146 Formula 1140:1146 Their structures, in order of abundance, were: (Formula: see text). 2580706 1 16 theme aqueous 289:295 arg1 ethanol 297:303 67% aqueous ethanol 285:303 67% aqueous ethanol 285:303 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 4 17 theme fast 941:944 arg1 bombardment 951:961 fast atom bombardment 941:961 fast atom bombardment 941:961 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 1 18 theme group 201:205 arg1 neonates 209:216 group O neonates 201:216 group O neonates of secretor type 201:233 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 0 19 theme oncofoetal 126:135 arg1 antigens 137:144 oncofoetal antigens 126:144 oncofoetal antigens 126:144 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. 2580706 2 20 theme hybridoma 513:521 arg1 FC 532:533 the hybridoma antibody FC 10.2 509:538 the hybridoma antibody FC 10.2 509:538 The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. 2580706 0 21 gly glycoproteins 98:110 arg1 glycoproteins 98:110 human meconium glycoproteins 83:110 human meconium glycoproteins which express oncofoetal antigens 83:144 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. 2580706 1 22 theme O 207:207 arg1 neonates 209:216 group O neonates 201:216 group O neonates of secretor type 201:233 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 2 23 theme mouse 494:498 arg1 sera 500:503 mouse sera 494:503 mouse sera 494:503 The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. 2580706 2 24 theme antibody 523:530 arg1 FC 532:533 the hybridoma antibody FC 10.2 509:538 the hybridoma antibody FC 10.2 509:538 The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. 2580706 1 25 theme neonates 209:216 arg1 samples 190:196 meconium samples 181:196 meconium samples of group O neonates of secretor type 181:233 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 0 26 theme Structural 0:9 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens 0:144 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. 2580706 3 27 theme performance 810:820 arg1 chromatography 829:842 Bio-Gel P4 and high performance liquid chromatography 790:842 chromatography 829:842 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 3 28 theme base-borohydride 712:727 arg1 degradation 729:739 base-borohydride degradation 712:739 base-borohydride degradation 712:739 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 0 29 link linked 44:49 arg1 oligosaccharides 63:78 the O-glycosidically linked core-region oligosaccharides 23:78 the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens 23:144 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. 2580706 3 30 theme liquid 822:827 arg1 chromatography 829:842 Bio-Gel P4 and high performance liquid chromatography 790:842 chromatography 829:842 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 2 31 theme acid 583:586 arg1 hydrolysis 588:597 mild acid hydrolysis 578:597 mild acid hydrolysis 578:597 The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. 2580706 1 32 theme secretor 221:228 arg1 type 230:233 secretor type 221:233 secretor type 221:233 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 2 33 theme natural 472:478 arg1 antibodies 480:489 natural antibodies 472:489 natural antibodies 472:489 The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. 2580706 2 34 theme mild 578:581 arg1 hydrolysis 588:597 mild acid hydrolysis 578:597 mild acid hydrolysis 578:597 The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. 2580706 3 35 theme mild-acid-treated 682:698 arg1 fraction 700:707 the mild-acid-treated fraction 678:707 the mild-acid-treated fraction 678:707 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 1 36 theme type 230:233 arg1 neonates 209:216 group O neonates 201:216 group O neonates of secretor type 201:233 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 0 37 theme linked 44:49 arg1 oligosaccharides 63:78 the O-glycosidically linked core-region oligosaccharides 23:78 the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens 23:144 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. 2580706 3 38 theme high 805:808 arg1 chromatography 829:842 Bio-Gel P4 and high performance liquid chromatography 790:842 chromatography 829:842 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 4 39 theme 500-MHz 1059:1065 arg1 spectroscopy 1078:1089 500-MHz proton NMR spectroscopy 1059:1089 500-MHz proton NMR spectroscopy 1059:1089 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 4 40 theme major 896:900 arg1 oligosaccharides 902:917 The major oligosaccharides 892:917 The major oligosaccharides 892:917 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 1 41 theme pronase 238:244 arg1 digestion 246:254 pronase digestion 238:254 pronase digestion followed by precipitation in 67% aqueous ethanol 238:303 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 0 42 theme oligosaccharides 63:78 arg1 analysis 11:18 Structural analysis 0:18 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens 0:144 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. 2580706 2 43 theme sialic 609:614 arg1 acid 616:619 sialic acid and fucose residues 609:639 acid 616:619 The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. 2580706 4 44 theme atom 946:949 arg1 bombardment 951:961 fast atom bombardment 941:961 fast atom bombardment 941:961 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 0 45 theme core-region 51:61 arg1 oligosaccharides 63:78 the O-glycosidically linked core-region oligosaccharides 23:78 the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens 23:144 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. 2580706 1 46 theme enriched 335:342 arg1 fractions 357:365 Ii antigen enriched and depleted fractions 324:365 Ii antigen enriched and depleted fractions 324:365 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 1 47 from precipitation 268:280 arg1 ethanol 297:303 67% aqueous ethanol 285:303 67% aqueous ethanol 285:303 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 3 48 theme gel 757:759 arg1 chromatography 772:785 gel permeation chromatography 757:785 gel permeation chromatography 757:785 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 3 49 attach released 664:671 arg2 Oligosaccharides 642:657 Oligosaccharides 642:657 Oligosaccharides 642:657 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 3 49 attach released 664:671 arg1 fraction 700:707 the mild-acid-treated fraction 678:707 the mild-acid-treated fraction 678:707 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 4 50 theme gas-liquid 1011:1020 arg1 spectrometry 1042:1053 combined gas-liquid chromatography/mass spectrometry 1002:1053 combined gas-liquid chromatography/mass spectrometry 1002:1053 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 4 51 theme combined 1002:1009 arg1 spectrometry 1042:1053 combined gas-liquid chromatography/mass spectrometry 1002:1053 combined gas-liquid chromatography/mass spectrometry 1002:1053 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 4 52 theme chromatography/mass 1022:1040 arg1 spectrometry 1042:1053 combined gas-liquid chromatography/mass spectrometry 1002:1053 combined gas-liquid chromatography/mass spectrometry 1002:1053 The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. 2580706 0 53 theme human 83:87 arg1 glycoproteins 98:110 human meconium glycoproteins 83:110 human meconium glycoproteins which express oncofoetal antigens 83:144 Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens. 2580706 2 54 theme oncofoetal 438:447 arg1 antigens 449:456 the oncofoetal antigens 434:456 the oncofoetal antigens recognised by natural antibodies 434:489 The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. 2580706 5 55 theme abundance 1122:1130 arg1 order 1113:1117 order 1113:1117 order of abundance 1113:1130 Their structures, in order of abundance, were: (Formula: see text). 2580706 2 56 theme latter 399:404 arg1 fraction 406:413 The latter fraction 395:413 The latter fraction 395:413 The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. 2580706 3 57 theme aminopropylsilyl 866:881 arg1 columns 883:889 aminopropylsilyl columns 866:889 aminopropylsilyl columns 866:889 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 1 58 theme depleted 348:355 arg1 fractions 357:365 Ii antigen enriched and depleted fractions 324:365 Ii antigen enriched and depleted fractions 324:365 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 2580706 3 59 from P4 798:799 arg1 octadecylsilyl 847:860 octadecylsilyl 847:860 octadecylsilyl 847:860 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 3 59 from P4 798:799 arg1 columns 883:889 aminopropylsilyl columns 866:889 aminopropylsilyl columns 866:889 Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. 2580706 1 60 theme meconium 181:188 arg1 samples 190:196 meconium samples 181:196 meconium samples of group O neonates of secretor type 181:233 Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. 8054719 0 0 theme non-secretor 84:95 arg1 patient 109:115 a non-secretor (O, Lea+b-) patient 82:115 a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis 82:149 Structures of monosialyl oligosaccharides isolated from the respiratory mucins of a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis. 8054719 10 1 theme patient 1389:1395 arg1 mucins 1362:1367 the mucins 1358:1367 the mucins of the non-secretor patient 1358:1395 Eight structures isolated from the mucins of the non-secretor patient had not been found previously in the respiratory mucins of secretor individuals; they are listed below. 8054719 10 2 theme individuals 1465:1475 arg1 mucins 1446:1451 the respiratory mucins 1430:1451 the respiratory mucins of secretor individuals 1430:1475 Eight structures isolated from the mucins of the non-secretor patient had not been found previously in the respiratory mucins of secretor individuals; they are listed below. 8054719 0 3 dep patient 109:115 arg1 O 98:98 O 98:98 O 98:98 Structures of monosialyl oligosaccharides isolated from the respiratory mucins of a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis. 8054719 0 3 dep patient 109:115 arg1 Lea+b- 101:106 Lea+b- 101:106 Lea+b- 101:106 Structures of monosialyl oligosaccharides isolated from the respiratory mucins of a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis. 8054719 4 4 theme 1H-NMR 619:624 arg1 spectroscopy 626:637 500-MHz 1H-NMR spectroscopy 611:637 500-MHz 1H-NMR spectroscopy 611:637 Structural studies employed 500-MHz 1H-NMR spectroscopy and fast atom bombardment-mass spectrometry. 8054719 8 5 theme alpha 1106:1110 arg1 linkage 1118:1124 alpha(-->3) linkage 1106:1124 alpha(-->3) linkage 1106:1124 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 7 6 theme non-secretor 957:968 arg1 status 970:975 the non-secretor status 953:975 the non-secretor status of the patient 953:990 In keeping with the non-secretor status of the patient, no structures with an alpha(-->2)-linked fucose residue were found. 8054719 3 7 theme liquid 523:528 arg1 chromatography 530:543 high-performance liquid chromatography 506:543 high-performance liquid chromatography 506:543 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 4 8 theme 500-MHz 611:617 arg1 spectroscopy 626:637 500-MHz 1H-NMR spectroscopy 611:637 500-MHz 1H-NMR spectroscopy 611:637 Structural studies employed 500-MHz 1H-NMR spectroscopy and fast atom bombardment-mass spectrometry. 8054719 9 9 link -linked 1293:1299 arg1 fucose 1273:1278 fucose 1273:1278 fucose alpha (1-->4)-linked in the Le(a) determinant 1273:1324 Only one oligosaccharide (structure 3b) was seen with fucose alpha (1-->4)-linked in the Le(a) determinant. 8054719 3 10 theme alkylamine 564:573 arg1 column 575:580 a silica-bonded alkylamine column 548:580 a silica-bonded alkylamine column 548:580 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 8 11 from determinant 1182:1192 arg1 present 1095:1101 present 1095:1101 present 1095:1101 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 12 from determinant 1147:1157 arg1 present 1095:1101 present 1095:1101 present 1095:1101 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 3 13 from chromatography 530:543 arg1 column 575:580 a silica-bonded alkylamine column 548:580 a silica-bonded alkylamine column 548:580 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 2 14 dep O 347:347 arg1 +b- 355:357 +b- 355:357 +b- 355:357 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 3 15 theme size-exclusion 472:485 arg1 chromatography 487:500 size-exclusion chromatography 472:500 size-exclusion chromatography 472:500 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 8 16 contain had 1084:1086 arg1 Nine 1061:1064 Nine 1061:1064 Nine 1061:1064 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 16 contain had 1084:1086 arg2 fucose 1088:1093 fucose 1088:1093 fucose 1088:1093 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 16 contain had 1084:1086 arg1 structures 1073:1082 the structures 1069:1082 the structures 1069:1082 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 16 contain had 1084:1086 arg2 structure 1204:1212 structure 11 1204:1215 structure 11 1204:1215 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 16 contain had 1084:1086 arg2 both 1198:1201 both 1198:1201 both 1198:1201 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 17 theme sialyl-Le 1169:1177 arg1 determinant 1182:1192 the sialyl-Le(x) determinant 1165:1192 the sialyl-Le(x) determinant 1165:1192 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 9 18 theme -linked 1293:1299 arg1 fucose 1273:1278 fucose 1273:1278 fucose alpha (1-->4)-linked in the Le(a) determinant 1273:1324 Only one oligosaccharide (structure 3b) was seen with fucose alpha (1-->4)-linked in the Le(a) determinant. 8054719 3 19 theme alkaline 394:401 arg1 treatment 415:423 alkaline borohydride treatment 394:423 alkaline borohydride treatment 394:423 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 9 20 theme a 1311:1311 arg1 determinant 1314:1324 the Le(a) determinant 1304:1324 the Le(a) determinant 1304:1324 Only one oligosaccharide (structure 3b) was seen with fucose alpha (1-->4)-linked in the Le(a) determinant. 8054719 5 21 theme Twenty-six 684:693 arg1 oligosaccharides 706:721 Twenty-six monosialyl oligosaccharides 684:721 Twenty-six monosialyl oligosaccharides 684:721 Twenty-six monosialyl oligosaccharides, ranging in size from di- to octasaccharide, were fully characterized in this study. 8054719 2 22 theme respiratory 266:276 arg1 mucus 278:282 the respiratory mucus 262:282 the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b- 262:357 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 10 23 theme non-secretor 1376:1387 arg1 patient 1389:1395 the non-secretor patient 1372:1395 the non-secretor patient 1372:1395 Eight structures isolated from the mucins of the non-secretor patient had not been found previously in the respiratory mucins of secretor individuals; they are listed below. 8054719 5 24 theme monosialyl 695:704 arg1 oligosaccharides 706:721 Twenty-six monosialyl oligosaccharides 684:721 Twenty-six monosialyl oligosaccharides 684:721 Twenty-six monosialyl oligosaccharides, ranging in size from di- to octasaccharide, were fully characterized in this study. 8054719 2 25 theme bronchitis 311:320 arg1 patient 322:328 a non-secretor, chronic bronchitis patient 287:328 a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b- 287:357 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 10 26 theme respiratory 1434:1444 arg1 mucins 1446:1451 the respiratory mucins 1430:1451 the respiratory mucins of secretor individuals 1430:1475 Eight structures isolated from the mucins of the non-secretor patient had not been found previously in the respiratory mucins of secretor individuals; they are listed below. 8054719 1 27 theme novel 174:178 arg1 type 180:183 a novel type 172:183 a novel type of mucin carbohydrate core structure 172:220 Characterization of a novel type of mucin carbohydrate core structure. 8054719 11 28 theme structure 1514:1522 arg1 alpha 1526:1530 structure 4 alpha 1514:1530 structure 4 alpha 1514:1530 Among these, structure 4 alpha represents a novel type of mucin carbohydrate core structure. 8054719 4 29 theme Structural 583:592 arg1 studies 594:600 Structural studies 583:600 Structural studies 583:600 Structural studies employed 500-MHz 1H-NMR spectroscopy and fast atom bombardment-mass spectrometry. 8054719 3 30 from chromatography 487:500 arg1 column 575:580 a silica-bonded alkylamine column 548:580 a silica-bonded alkylamine column 548:580 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 1 31 theme type 180:183 arg1 Characterization 152:167 Characterization 152:167 Characterization of a novel type of mucin carbohydrate core structure. 152:221 Characterization of a novel type of mucin carbohydrate core structure. 8054719 0 32 theme oligosaccharides 25:40 arg1 Structures 0:9 Structures 0:9 Structures of monosialyl oligosaccharides 0:40 Structures of monosialyl oligosaccharides isolated from the respiratory mucins of a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis. 8054719 9 33 attach -linked 1293:1299 arg3 determinant 1314:1324 the Le(a) determinant 1304:1324 the Le(a) determinant 1304:1324 Only one oligosaccharide (structure 3b) was seen with fucose alpha (1-->4)-linked in the Le(a) determinant. 8054719 0 34 theme patient 109:115 arg1 mucins 72:77 the respiratory mucins 56:77 the respiratory mucins of a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis 56:149 Structures of monosialyl oligosaccharides isolated from the respiratory mucins of a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis. 8054719 8 35 theme Le 1141:1142 arg1 determinant 1147:1157 the Le(x) determinant 1137:1157 the Le(x) determinant 1137:1157 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 36 theme x 1144:1144 arg1 determinant 1147:1157 the Le(x) determinant 1137:1157 the Le(x) determinant 1137:1157 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 3 37 theme anion-exchange 441:454 arg1 chromatography 456:469 anion-exchange chromatography 441:469 anion-exchange chromatography 441:469 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 0 38 theme monosialyl 14:23 arg1 oligosaccharides 25:40 monosialyl oligosaccharides 14:40 monosialyl oligosaccharides 14:40 Structures of monosialyl oligosaccharides isolated from the respiratory mucins of a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis. 8054719 9 39 from -linked 1293:1299 arg1 determinant 1314:1324 the Le(a) determinant 1304:1324 the Le(a) determinant 1304:1324 Only one oligosaccharide (structure 3b) was seen with fucose alpha (1-->4)-linked in the Le(a) determinant. 8054719 2 40 theme non-secretor 289:300 arg1 patient 322:328 a non-secretor, chronic bronchitis patient 287:328 a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b- 287:357 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 1 41 theme mucin 188:192 arg1 structure 212:220 mucin carbohydrate core structure 188:220 mucin carbohydrate core structure 188:220 Characterization of a novel type of mucin carbohydrate core structure. 8054719 3 42 theme high-performance 506:521 arg1 chromatography 530:543 high-performance liquid chromatography 506:543 high-performance liquid chromatography 506:543 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 2 43 dep non-secretor 289:300 arg1 chronic 303:309 chronic 303:309 chronic 303:309 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 7 44 theme -linked 1026:1032 arg1 residue 1041:1047 an alpha(-->2)-linked fucose residue 1012:1047 an alpha(-->2)-linked fucose residue 1012:1047 In keeping with the non-secretor status of the patient, no structures with an alpha(-->2)-linked fucose residue were found. 8054719 2 45 with patient 322:328 arg1 Le 350:351 Le 350:351 Le(a) 350:354 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 2 45 with patient 322:328 arg1 O 347:347 blood group O 335:347 blood group O 335:347 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 3 46 theme borohydride 403:413 arg1 treatment 415:423 alkaline borohydride treatment 394:423 alkaline borohydride treatment 394:423 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 1 47 theme carbohydrate 194:205 arg1 structure 212:220 mucin carbohydrate core structure 188:220 mucin carbohydrate core structure 188:220 Characterization of a novel type of mucin carbohydrate core structure. 8054719 2 48 gly glycopeptides 229:241 arg2 glycopeptides 229:241 Mucin glycopeptides 223:241 Mucin glycopeptides 223:241 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 9 49 theme structure 1245:1253 arg1 oligosaccharide 1228:1242 Only one oligosaccharide 1219:1242 Only one oligosaccharide (structure 3b) 1219:1257 Only one oligosaccharide (structure 3b) was seen with fucose alpha (1-->4)-linked in the Le(a) determinant. 8054719 9 49 theme structure 1245:1253 arg1 3b 1255:1256 structure 3b 1245:1256 structure 3b 1245:1256 Only one oligosaccharide (structure 3b) was seen with fucose alpha (1-->4)-linked in the Le(a) determinant. 8054719 7 50 theme fucose 1034:1039 arg1 residue 1041:1047 an alpha(-->2)-linked fucose residue 1012:1047 an alpha(-->2)-linked fucose residue 1012:1047 In keeping with the non-secretor status of the patient, no structures with an alpha(-->2)-linked fucose residue were found. 8054719 7 51 with structures 996:1005 arg1 residue 1041:1047 an alpha(-->2)-linked fucose residue 1012:1047 an alpha(-->2)-linked fucose residue 1012:1047 In keeping with the non-secretor status of the patient, no structures with an alpha(-->2)-linked fucose residue were found. 8054719 2 52 theme Mucin 223:227 arg1 glycopeptides 229:241 Mucin glycopeptides 223:241 Mucin glycopeptides 223:241 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 9 53 from determinant 1314:1324 arg1 -linked 1293:1299 -linked 1293:1299 -linked 1293:1299 Only one oligosaccharide (structure 3b) was seen with fucose alpha (1-->4)-linked in the Le(a) determinant. 8054719 1 54 theme core 207:210 arg1 structure 212:220 mucin carbohydrate core structure 188:220 mucin carbohydrate core structure 188:220 Characterization of a novel type of mucin carbohydrate core structure. 8054719 0 55 theme respiratory 60:70 arg1 mucins 72:77 the respiratory mucins 56:77 the respiratory mucins of a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis 56:149 Structures of monosialyl oligosaccharides isolated from the respiratory mucins of a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis. 8054719 8 56 theme structures 1073:1082 arg1 Nine 1061:1064 Nine 1061:1064 Nine 1061:1064 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 56 theme structures 1073:1082 arg1 structures 1073:1082 the structures 1069:1082 the structures 1069:1082 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 57 from present 1095:1101 arg1 determinant 1147:1157 the Le(x) determinant 1137:1157 the Le(x) determinant 1137:1157 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 57 from present 1095:1101 arg1 linkage 1118:1124 alpha(-->3) linkage 1106:1124 alpha(-->3) linkage 1106:1124 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 57 from present 1095:1101 arg1 determinant 1182:1192 the sialyl-Le(x) determinant 1165:1192 the sialyl-Le(x) determinant 1165:1192 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 2 58 theme group 341:345 arg1 Le 350:351 Le 350:351 Le(a) 350:354 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 2 58 theme group 341:345 arg1 O 347:347 blood group O 335:347 blood group O 335:347 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 10 59 theme secretor 1456:1463 arg1 individuals 1465:1475 secretor individuals 1456:1475 secretor individuals 1456:1475 Eight structures isolated from the mucins of the non-secretor patient had not been found previously in the respiratory mucins of secretor individuals; they are listed below. 8054719 0 60 theme chronic 132:138 arg1 bronchitis 140:149 chronic bronchitis 132:149 chronic bronchitis 132:149 Structures of monosialyl oligosaccharides isolated from the respiratory mucins of a non-secretor (O, Lea+b-) patient suffering from chronic bronchitis. 8054719 11 61 theme mucin 1559:1563 arg1 structure 1583:1591 mucin carbohydrate core structure 1559:1591 mucin carbohydrate core structure 1559:1591 Among these, structure 4 alpha represents a novel type of mucin carbohydrate core structure. 8054719 6 62 theme sialic 812:817 arg1 acid 819:822 The sialic acid 808:822 The sialic acid 808:822 The sialic acid occurs either alpha(2-->3)- or alpha(2-->6)-linked to a galactosyl residue, or alpha(2-->6)-linked to GalNAc-ol. 8054719 2 63 theme blood 335:339 arg1 Le 350:351 Le 350:351 Le(a) 350:354 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 2 63 theme blood 335:339 arg1 O 347:347 blood group O 335:347 blood group O 335:347 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 10 64 located found 1410:1414 arg1 mucins 1446:1451 the respiratory mucins 1430:1451 the respiratory mucins of secretor individuals 1430:1475 Eight structures isolated from the mucins of the non-secretor patient had not been found previously in the respiratory mucins of secretor individuals; they are listed below. 8054719 10 64 located found 1410:1414 arg2 structures 1333:1342 Eight structures 1327:1342 Eight structures isolated from the mucins of the non-secretor patient 1327:1395 Eight structures isolated from the mucins of the non-secretor patient had not been found previously in the respiratory mucins of secretor individuals; they are listed below. 8054719 8 65 from linkage 1118:1124 arg1 present 1095:1101 present 1095:1101 present 1095:1101 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 3 66 from chromatography 456:469 arg1 column 575:580 a silica-bonded alkylamine column 548:580 a silica-bonded alkylamine column 548:580 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 1 67 theme structure 212:220 arg1 type 180:183 a novel type 172:183 a novel type of mucin carbohydrate core structure 172:220 Characterization of a novel type of mucin carbohydrate core structure. 8054719 3 68 theme silica-bonded 550:562 arg1 column 575:580 a silica-bonded alkylamine column 548:580 a silica-bonded alkylamine column 548:580 Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high-performance liquid chromatography on a silica-bonded alkylamine column. 8054719 11 69 theme novel 1545:1549 arg1 type 1551:1554 a novel type 1543:1554 a novel type of mucin carbohydrate core structure 1543:1591 Among these, structure 4 alpha represents a novel type of mucin carbohydrate core structure. 8054719 8 70 attach present 1095:1101 arg2 fucose 1088:1093 fucose 1088:1093 fucose 1088:1093 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 70 attach present 1095:1101 arg1 determinant 1147:1157 the Le(x) determinant 1137:1157 the Le(x) determinant 1137:1157 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 70 attach present 1095:1101 arg1 linkage 1118:1124 alpha(-->3) linkage 1106:1124 alpha(-->3) linkage 1106:1124 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 8 70 attach present 1095:1101 arg1 determinant 1182:1192 the sialyl-Le(x) determinant 1165:1192 the sialyl-Le(x) determinant 1165:1192 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 7 71 theme patient 984:990 arg1 status 970:975 the non-secretor status 953:975 the non-secretor status of the patient 953:990 In keeping with the non-secretor status of the patient, no structures with an alpha(-->2)-linked fucose residue were found. 8054719 2 72 theme patient 322:328 arg1 mucus 278:282 the respiratory mucus 262:282 the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b- 262:357 Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a)+b-. 8054719 4 73 theme fast 643:646 arg1 spectrometry 670:681 fast atom bombardment-mass spectrometry 643:681 fast atom bombardment-mass spectrometry 643:681 Structural studies employed 500-MHz 1H-NMR spectroscopy and fast atom bombardment-mass spectrometry. 8054719 6 74 theme galactosyl 880:889 arg1 residue 891:897 a galactosyl residue 878:897 a galactosyl residue 878:897 The sialic acid occurs either alpha(2-->3)- or alpha(2-->6)-linked to a galactosyl residue, or alpha(2-->6)-linked to GalNAc-ol. 8054719 11 75 theme structure 1583:1591 arg1 type 1551:1554 a novel type 1543:1554 a novel type of mucin carbohydrate core structure 1543:1591 Among these, structure 4 alpha represents a novel type of mucin carbohydrate core structure. 8054719 10 76 attach isolated 1344:1351 arg1 mucins 1362:1367 the mucins 1358:1367 the mucins of the non-secretor patient 1358:1395 Eight structures isolated from the mucins of the non-secretor patient had not been found previously in the respiratory mucins of secretor individuals; they are listed below. 8054719 10 76 attach isolated 1344:1351 arg2 structures 1333:1342 Eight structures 1327:1342 Eight structures isolated from the mucins of the non-secretor patient 1327:1395 Eight structures isolated from the mucins of the non-secretor patient had not been found previously in the respiratory mucins of secretor individuals; they are listed below. 8054719 8 77 theme x 1179:1179 arg1 determinant 1182:1192 the sialyl-Le(x) determinant 1165:1192 the sialyl-Le(x) determinant 1165:1192 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 7 78 link -linked 1026:1032 arg1 residue 1041:1047 an alpha(-->2)-linked fucose residue 1012:1047 an alpha(-->2)-linked fucose residue 1012:1047 In keeping with the non-secretor status of the patient, no structures with an alpha(-->2)-linked fucose residue were found. 8054719 11 79 theme carbohydrate 1565:1576 arg1 structure 1583:1591 mucin carbohydrate core structure 1559:1591 mucin carbohydrate core structure 1559:1591 Among these, structure 4 alpha represents a novel type of mucin carbohydrate core structure. 8054719 8 80 theme present 1095:1101 arg1 fucose 1088:1093 fucose 1088:1093 fucose 1088:1093 Nine of the structures had fucose present in alpha(-->3) linkage, either in the Le(x) determinant or in the sialyl-Le(x) determinant, or both (structure 11). 8054719 9 81 theme Le 1308:1309 arg1 determinant 1314:1324 the Le(a) determinant 1304:1324 the Le(a) determinant 1304:1324 Only one oligosaccharide (structure 3b) was seen with fucose alpha (1-->4)-linked in the Le(a) determinant. 8054719 11 82 theme core 1578:1581 arg1 structure 1583:1591 mucin carbohydrate core structure 1559:1591 mucin carbohydrate core structure 1559:1591 Among these, structure 4 alpha represents a novel type of mucin carbohydrate core structure. 8054719 4 83 theme atom 648:651 arg1 spectrometry 670:681 fast atom bombardment-mass spectrometry 643:681 fast atom bombardment-mass spectrometry 643:681 Structural studies employed 500-MHz 1H-NMR spectroscopy and fast atom bombardment-mass spectrometry. 8054719 4 84 theme bombardment-mass 653:668 arg1 spectrometry 670:681 fast atom bombardment-mass spectrometry 643:681 fast atom bombardment-mass spectrometry 643:681 Structural studies employed 500-MHz 1H-NMR spectroscopy and fast atom bombardment-mass spectrometry. 8416919 0 0 theme urinary 94:100 arg1 kallidinogenase 102:116 human urinary kallidinogenase 88:116 human urinary kallidinogenase 88:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 4 1 theme reducing 542:549 arg1 ends 551:554 The reducing ends 538:554 The reducing ends of the oligosaccharide chains 538:584 The reducing ends of the oligosaccharide chains were aminated with a fluorescent reagent, 2-aminopyridine. 8416919 4 1 theme reducing 542:549 arg1 aminated 591:598 aminated 591:598 aminated 591:598 The reducing ends of the oligosaccharide chains were aminated with a fluorescent reagent, 2-aminopyridine. 8416919 1 2 from kallidinogenase 223:237 arg1 oligosaccharides 187:202 terminal GalNAc-containing N-linked oligosaccharides 151:202 terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 151:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 8416919 1 2 from kallidinogenase 223:237 arg1 structures 137:146 Fifteen different structures 119:146 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 119:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 8416919 6 3 theme resolution 965:974 arg1 resonance 1000:1008 high resolution proton nuclear magnetic resonance 960:1008 high resolution proton nuclear magnetic resonance 960:1008 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 0 4 theme human 88:92 arg1 kallidinogenase 102:116 human urinary kallidinogenase 88:116 human urinary kallidinogenase 88:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 5 5 theme resulting 649:657 arg1 mixture 659:665 The resulting mixture 645:665 The resulting mixture of pyridylamino derivatives of the oligosaccharides 645:717 The resulting mixture of pyridylamino derivatives of the oligosaccharides were separated by high performance liquid chromatography on an ODS-silica column, and 15 oligosaccharides were isolated. 8416919 1 6 theme human 209:213 arg1 kallidinogenase 223:237 human urinary kallidinogenase 209:237 human urinary kallidinogenase 209:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 8416919 7 7 contain contains 1130:1137 arg2 oligosaccharide 1068:1082 each N-linked oligosaccharide 1054:1082 each N-linked oligosaccharide associated with human urinary kallidinogenase 1054:1128 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 7 7 contain contains 1130:1137 arg2 residues 1160:1167 unsubstituted GalNAc residues 1139:1167 unsubstituted GalNAc residues 1139:1167 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 7 7 contain contains 1130:1137 arg1 terminal 1188:1195 the nonreducing terminal 1172:1195 the nonreducing terminal 1172:1195 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 7 7 contain contains 1130:1137 arg1 oligosaccharide 1068:1082 each N-linked oligosaccharide 1054:1082 each N-linked oligosaccharide associated with human urinary kallidinogenase 1054:1128 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 6 8 theme sugar 919:923 arg1 mapping 925:931 two-dimensional sugar mapping 903:931 two-dimensional sugar mapping 903:931 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 7 9 link N-linked 1059:1066 arg1 oligosaccharide 1068:1082 each N-linked oligosaccharide 1054:1082 each N-linked oligosaccharide associated with human urinary kallidinogenase 1054:1128 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 4 10 with aminated 591:598 arg1 2-aminopyridine 628:642 2-aminopyridine 628:642 2-aminopyridine 628:642 The reducing ends of the oligosaccharide chains were aminated with a fluorescent reagent, 2-aminopyridine. 8416919 4 10 with aminated 591:598 arg1 reagent 619:625 a fluorescent reagent 605:625 a fluorescent reagent 605:625 The reducing ends of the oligosaccharide chains were aminated with a fluorescent reagent, 2-aminopyridine. 8416919 6 11 theme magnetic 991:998 arg1 resonance 1000:1008 high resolution proton nuclear magnetic resonance 960:1008 high resolution proton nuclear magnetic resonance 960:1008 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 5 12 theme high 737:740 arg1 chromatography 761:774 high performance liquid chromatography 737:774 high performance liquid chromatography on an ODS-silica column 737:798 The resulting mixture of pyridylamino derivatives of the oligosaccharides were separated by high performance liquid chromatography on an ODS-silica column, and 15 oligosaccharides were isolated. 8416919 7 13 theme N-linked 1059:1066 arg1 oligosaccharide 1068:1082 each N-linked oligosaccharide 1054:1082 each N-linked oligosaccharide associated with human urinary kallidinogenase 1054:1128 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 2 14 theme acid/mol 376:383 arg1 mol 362:364 0.13 mol 357:364 0.13 mol of sialic acid/mol of sugar chain 357:398 These N-linked oligosaccharides were mostly neutral, because sialic acid content was lower than 0.13 mol of sialic acid/mol of sugar chain, and sulfate was not detected. 8416919 6 15 theme nuclear 983:989 arg1 resonance 1000:1008 high resolution proton nuclear magnetic resonance 960:1008 high resolution proton nuclear magnetic resonance 960:1008 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 5 16 theme derivatives 683:693 arg1 mixture 659:665 The resulting mixture 645:665 The resulting mixture of pyridylamino derivatives of the oligosaccharides 645:717 The resulting mixture of pyridylamino derivatives of the oligosaccharides were separated by high performance liquid chromatography on an ODS-silica column, and 15 oligosaccharides were isolated. 8416919 5 17 theme pyridylamino 670:681 arg1 derivatives 683:693 pyridylamino derivatives 670:693 pyridylamino derivatives of the oligosaccharides 670:717 The resulting mixture of pyridylamino derivatives of the oligosaccharides were separated by high performance liquid chromatography on an ODS-silica column, and 15 oligosaccharides were isolated. 8416919 1 18 theme urinary 215:221 arg1 kallidinogenase 223:237 human urinary kallidinogenase 209:237 human urinary kallidinogenase 209:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 8416919 6 19 theme proton 976:981 arg1 resonance 1000:1008 high resolution proton nuclear magnetic resonance 960:1008 high resolution proton nuclear magnetic resonance 960:1008 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 0 20 link N-linked 57:64 arg1 oligosaccharides 66:81 GalNAc-containing N-linked oligosaccharides 39:81 GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 39:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 3 21 theme glycoamidase 498:509 arg1 A 511:511 glycoamidase A 498:511 glycoamidase A (from almond) digestion 498:535 The oligosaccharides were released from pepsin-digested protein by glycoamidase A (from almond) digestion. 8416919 0 22 from variety 28:34 arg1 kallidinogenase 102:116 human urinary kallidinogenase 88:116 human urinary kallidinogenase 88:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 6 23 theme oligosaccharide 862:876 arg1 fraction 878:885 each oligosaccharide fraction 857:885 each oligosaccharide fraction 857:885 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 2 24 theme sialic 369:374 arg1 acid/mol 376:383 sialic acid/mol 369:383 sialic acid/mol of sugar chain 369:398 These N-linked oligosaccharides were mostly neutral, because sialic acid content was lower than 0.13 mol of sialic acid/mol of sugar chain, and sulfate was not detected. 8416919 7 25 theme nonreducing 1176:1186 arg1 terminal 1188:1195 the nonreducing terminal 1172:1195 the nonreducing terminal 1172:1195 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 3 26 theme pepsin-digested 471:485 arg1 protein 487:493 pepsin-digested protein 471:493 pepsin-digested protein 471:493 The oligosaccharides were released from pepsin-digested protein by glycoamidase A (from almond) digestion. 8416919 0 27 theme Structural 0:9 arg1 elucidation 11:21 Structural elucidation 0:21 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 0:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 5 28 theme oligosaccharides 702:717 arg1 derivatives 683:693 pyridylamino derivatives 670:693 pyridylamino derivatives of the oligosaccharides 670:717 The resulting mixture of pyridylamino derivatives of the oligosaccharides were separated by high performance liquid chromatography on an ODS-silica column, and 15 oligosaccharides were isolated. 8416919 1 29 from structures 137:146 arg1 kallidinogenase 223:237 human urinary kallidinogenase 209:237 human urinary kallidinogenase 209:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 8416919 6 30 theme component 934:942 arg1 analysis 950:957 component sugar analysis 934:957 component sugar analysis 934:957 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 6 31 theme two-dimensional 903:917 arg1 mapping 925:931 two-dimensional sugar mapping 903:931 two-dimensional sugar mapping 903:931 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 5 32 theme ODS-silica 782:791 arg1 column 793:798 an ODS-silica column 779:798 an ODS-silica column 779:798 The resulting mixture of pyridylamino derivatives of the oligosaccharides were separated by high performance liquid chromatography on an ODS-silica column, and 15 oligosaccharides were isolated. 8416919 6 33 theme high 960:963 arg1 resonance 1000:1008 high resolution proton nuclear magnetic resonance 960:1008 high resolution proton nuclear magnetic resonance 960:1008 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 1 34 theme different 127:135 arg1 structures 137:146 Fifteen different structures 119:146 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 119:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 8416919 6 35 theme methylation 1014:1024 arg1 analysis 1026:1033 methylation analysis 1014:1033 methylation analysis 1014:1033 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 4 36 theme fluorescent 607:617 arg1 2-aminopyridine 628:642 2-aminopyridine 628:642 2-aminopyridine 628:642 The reducing ends of the oligosaccharide chains were aminated with a fluorescent reagent, 2-aminopyridine. 8416919 4 36 theme fluorescent 607:617 arg1 reagent 619:625 a fluorescent reagent 605:625 a fluorescent reagent 605:625 The reducing ends of the oligosaccharide chains were aminated with a fluorescent reagent, 2-aminopyridine. 8416919 1 37 link N-linked 178:185 arg1 oligosaccharides 187:202 terminal GalNAc-containing N-linked oligosaccharides 151:202 terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 151:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 8416919 3 38 attach released 457:464 arg2 oligosaccharides 435:450 The oligosaccharides 431:450 The oligosaccharides 431:450 The oligosaccharides were released from pepsin-digested protein by glycoamidase A (from almond) digestion. 8416919 3 38 attach released 457:464 arg1 protein 487:493 pepsin-digested protein 471:493 pepsin-digested protein 471:493 The oligosaccharides were released from pepsin-digested protein by glycoamidase A (from almond) digestion. 8416919 2 39 link N-linked 267:274 arg1 oligosaccharides 276:291 These N-linked oligosaccharides 261:291 These N-linked oligosaccharides 261:291 These N-linked oligosaccharides were mostly neutral, because sialic acid content was lower than 0.13 mol of sialic acid/mol of sugar chain, and sulfate was not detected. 8416919 0 40 theme variety 28:34 arg1 elucidation 11:21 Structural elucidation 0:21 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 0:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 4 41 theme chains 579:584 arg1 ends 551:554 The reducing ends 538:554 The reducing ends of the oligosaccharide chains 538:584 The reducing ends of the oligosaccharide chains were aminated with a fluorescent reagent, 2-aminopyridine. 8416919 4 41 theme chains 579:584 arg1 aminated 591:598 aminated 591:598 aminated 591:598 The reducing ends of the oligosaccharide chains were aminated with a fluorescent reagent, 2-aminopyridine. 8416919 8 42 theme tetraantennary 1269:1282 arg1 oligosaccharides 1284:1299 3 tetraantennary oligosaccharides 1267:1299 3 tetraantennary oligosaccharides 1267:1299 These 15 oligosaccharides include 5 biantennary, 7 triantennary, and 3 tetraantennary oligosaccharides. 8416919 7 43 theme unsubstituted 1139:1151 arg1 residues 1160:1167 unsubstituted GalNAc residues 1139:1167 unsubstituted GalNAc residues 1139:1167 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 0 44 theme N-linked 57:64 arg1 oligosaccharides 66:81 GalNAc-containing N-linked oligosaccharides 39:81 GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 39:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 4 45 theme oligosaccharide 563:577 arg1 chains 579:584 the oligosaccharide chains 559:584 the oligosaccharide chains 559:584 The reducing ends of the oligosaccharide chains were aminated with a fluorescent reagent, 2-aminopyridine. 8416919 5 46 theme performance 742:752 arg1 chromatography 761:774 high performance liquid chromatography 737:774 high performance liquid chromatography on an ODS-silica column 737:798 The resulting mixture of pyridylamino derivatives of the oligosaccharides were separated by high performance liquid chromatography on an ODS-silica column, and 15 oligosaccharides were isolated. 8416919 6 47 theme sugar 944:948 arg1 analysis 950:957 component sugar analysis 934:957 component sugar analysis 934:957 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 7 48 theme GalNAc 1153:1158 arg1 residues 1160:1167 unsubstituted GalNAc residues 1139:1167 unsubstituted GalNAc residues 1139:1167 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 2 49 theme chain 394:398 arg1 acid/mol 376:383 sialic acid/mol 369:383 sialic acid/mol of sugar chain 369:398 These N-linked oligosaccharides were mostly neutral, because sialic acid content was lower than 0.13 mol of sialic acid/mol of sugar chain, and sulfate was not detected. 8416919 0 50 theme GalNAc-containing 39:55 arg1 oligosaccharides 66:81 GalNAc-containing N-linked oligosaccharides 39:81 GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 39:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 5 51 theme liquid 754:759 arg1 chromatography 761:774 high performance liquid chromatography 737:774 high performance liquid chromatography on an ODS-silica column 737:798 The resulting mixture of pyridylamino derivatives of the oligosaccharides were separated by high performance liquid chromatography on an ODS-silica column, and 15 oligosaccharides were isolated. 8416919 2 52 theme N-linked 267:274 arg1 oligosaccharides 276:291 These N-linked oligosaccharides 261:291 These N-linked oligosaccharides 261:291 These N-linked oligosaccharides were mostly neutral, because sialic acid content was lower than 0.13 mol of sialic acid/mol of sugar chain, and sulfate was not detected. 8416919 2 53 theme sugar 388:392 arg1 chain 394:398 sugar chain 388:398 sugar chain 388:398 These N-linked oligosaccharides were mostly neutral, because sialic acid content was lower than 0.13 mol of sialic acid/mol of sugar chain, and sulfate was not detected. 8416919 6 54 theme fraction 878:885 arg1 structure 844:852 The structure 840:852 The structure of each oligosaccharide fraction 840:885 The structure of each oligosaccharide fraction was analyzed by two-dimensional sugar mapping, component sugar analysis, high resolution proton nuclear magnetic resonance and methylation analysis. 8416919 2 55 theme acid 329:332 arg1 content 334:340 sialic acid content 322:340 sialic acid content 322:340 These N-linked oligosaccharides were mostly neutral, because sialic acid content was lower than 0.13 mol of sialic acid/mol of sugar chain, and sulfate was not detected. 8416919 3 56 from almond 519:524 arg1 A 511:511 glycoamidase A 498:511 glycoamidase A (from almond) digestion 498:535 The oligosaccharides were released from pepsin-digested protein by glycoamidase A (from almond) digestion. 8416919 1 57 theme terminal 151:158 arg1 oligosaccharides 187:202 terminal GalNAc-containing N-linked oligosaccharides 151:202 terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 151:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 8416919 5 58 from chromatography 761:774 arg1 column 793:798 an ODS-silica column 779:798 an ODS-silica column 779:798 The resulting mixture of pyridylamino derivatives of the oligosaccharides were separated by high performance liquid chromatography on an ODS-silica column, and 15 oligosaccharides were isolated. 8416919 2 59 theme sialic 322:327 arg1 acid 329:332 sialic acid 322:332 sialic acid content 322:340 These N-linked oligosaccharides were mostly neutral, because sialic acid content was lower than 0.13 mol of sialic acid/mol of sugar chain, and sulfate was not detected. 8416919 7 60 theme human 1100:1104 arg1 kallidinogenase 1114:1128 human urinary kallidinogenase 1100:1128 human urinary kallidinogenase 1100:1128 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 1 61 theme GalNAc-containing 160:176 arg1 oligosaccharides 187:202 terminal GalNAc-containing N-linked oligosaccharides 151:202 terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 151:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 8416919 0 62 from kallidinogenase 102:116 arg1 oligosaccharides 66:81 GalNAc-containing N-linked oligosaccharides 39:81 GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 39:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 0 62 from kallidinogenase 102:116 arg1 variety 28:34 a variety 26:34 a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 26:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 3 63 theme A 511:511 arg1 digestion 527:535 glycoamidase A (from almond) digestion 498:535 glycoamidase A (from almond) digestion 498:535 The oligosaccharides were released from pepsin-digested protein by glycoamidase A (from almond) digestion. 8416919 7 64 theme urinary 1106:1112 arg1 kallidinogenase 1114:1128 human urinary kallidinogenase 1100:1128 human urinary kallidinogenase 1100:1128 It was found that each N-linked oligosaccharide associated with human urinary kallidinogenase contains unsubstituted GalNAc residues at the nonreducing terminal. 8416919 1 65 theme N-linked 178:185 arg1 oligosaccharides 187:202 terminal GalNAc-containing N-linked oligosaccharides 151:202 terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 151:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 8416919 0 66 theme oligosaccharides 66:81 arg1 oligosaccharides 66:81 GalNAc-containing N-linked oligosaccharides 39:81 GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 39:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 0 66 theme oligosaccharides 66:81 arg1 variety 28:34 a variety 26:34 a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 26:116 Structural elucidation of a variety of GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase. 8416919 1 67 theme oligosaccharides 187:202 arg1 structures 137:146 Fifteen different structures 119:146 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase 119:237 Fifteen different structures of terminal GalNAc-containing N-linked oligosaccharides from human urinary kallidinogenase have been identified. 3442327 4 0 theme oligomannose-type 625:641 arg1 chains 649:654 oligomannose-type sugar chains 625:654 oligomannose-type sugar chains of human C3, the third component of human complement 625:707 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 0 1 theme processing 78:87 arg1 intermediates 89:101 processing intermediates 78:101 processing intermediates of glycoproteins 78:118 Identification method for twelve oligomannose-type sugar chains thought to be processing intermediates of glycoproteins. 3442327 1 2 theme derivatives 156:166 arg1 mixture 123:129 A mixture 121:129 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains 121:203 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 1 3 theme mannose9N-acetylglucosamine2-PA 289:319 arg1 mannose5N-acetylglucosamine2-PA 243:273 mannose5N-acetylglucosamine2-PA 243:273 mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA 243:319 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 0 4 theme glycoproteins 106:118 arg1 intermediates 89:101 processing intermediates 78:101 processing intermediates of glycoproteins 78:118 Identification method for twelve oligomannose-type sugar chains thought to be processing intermediates of glycoproteins. 3442327 4 5 theme chains 649:654 arg1 structures 611:620 the structures 607:620 the structures of oligomannose-type sugar chains of human C3, the third component of human complement 607:707 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 4 6 theme sugar 643:647 arg1 chains 649:654 oligomannose-type sugar chains 625:654 oligomannose-type sugar chains of human C3, the third component of human complement 625:707 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 4 7 theme complement 698:707 arg1 component 679:687 the third component 669:687 the third component of human complement 669:707 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 4 7 theme complement 698:707 arg1 C3 665:666 human C3 659:666 human C3 659:666 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 4 8 used used 590:593 arg2 method 579:584 The method 575:584 The method 575:584 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 4 9 theme human 692:696 arg1 complement 698:707 human complement 692:707 human complement 692:707 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 1 10 theme oligomannose-type 174:190 arg1 chains 198:203 12 oligomannose-type sugar chains 171:203 12 oligomannose-type sugar chains 171:203 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 0 11 theme Identification 0:13 arg1 method 15:20 Identification method 0:20 Identification method for twelve oligomannose-type sugar chains 0:62 Identification method for twelve oligomannose-type sugar chains thought to be processing intermediates of glycoproteins. 3442327 1 12 theme size-fractionation 325:342 arg1 HPLC 344:347 size-fractionation HPLC 325:347 size-fractionation HPLC with a MicroPak AX-5 column 325:375 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 0 13 gly glycoproteins 106:118 arg1 glycoproteins 106:118 glycoproteins 106:118 glycoproteins 106:118 Identification method for twelve oligomannose-type sugar chains thought to be processing intermediates of glycoproteins. 3442327 2 14 theme reversed-phase 427:440 arg1 HPLC 442:445 reversed-phase HPLC 427:445 reversed-phase HPLC 427:445 Each fraction thus obtained was then analyzed by reversed-phase HPLC with a Cosmosil 5C18-P column. 3442327 1 15 with HPLC 344:347 arg1 column 370:375 a MicroPak AX-5 column 354:375 a MicroPak AX-5 column 354:375 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 3 16 theme PA-oligomannose-type 498:517 arg1 chains 525:530 the 12 PA-oligomannose-type sugar chains 491:530 the 12 PA-oligomannose-type sugar chains 491:530 In this way, the 12 PA-oligomannose-type sugar chains were completely separated from each other. 3442327 3 17 theme sugar 519:523 arg1 chains 525:530 the 12 PA-oligomannose-type sugar chains 491:530 the 12 PA-oligomannose-type sugar chains 491:530 In this way, the 12 PA-oligomannose-type sugar chains were completely separated from each other. 3442327 0 18 theme sugar 51:55 arg1 chains 57:62 twelve oligomannose-type sugar chains 26:62 twelve oligomannose-type sugar chains 26:62 Identification method for twelve oligomannose-type sugar chains thought to be processing intermediates of glycoproteins. 3442327 1 19 theme sugar 192:196 arg1 chains 198:203 12 oligomannose-type sugar chains 171:203 12 oligomannose-type sugar chains 171:203 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 2 20 theme 5C18-P 463:468 arg1 column 470:475 a Cosmosil 5C18-P column 452:475 a Cosmosil 5C18-P column 452:475 Each fraction thus obtained was then analyzed by reversed-phase HPLC with a Cosmosil 5C18-P column. 3442327 0 21 theme oligomannose-type 33:49 arg1 chains 57:62 twelve oligomannose-type sugar chains 26:62 twelve oligomannose-type sugar chains 26:62 Identification method for twelve oligomannose-type sugar chains thought to be processing intermediates of glycoproteins. 3442327 1 22 theme MicroPak 356:363 arg1 column 370:375 a MicroPak AX-5 column 354:375 a MicroPak AX-5 column 354:375 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 2 23 theme Cosmosil 454:461 arg1 column 470:475 a Cosmosil 5C18-P column 452:475 a Cosmosil 5C18-P column 452:475 Each fraction thus obtained was then analyzed by reversed-phase HPLC with a Cosmosil 5C18-P column. 3442327 1 24 theme AX-5 365:368 arg1 column 370:375 a MicroPak AX-5 column 354:375 a MicroPak AX-5 column 354:375 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 1 25 dep fractions 232:240 arg1 mannose5N-acetylglucosamine2-PA 243:273 mannose5N-acetylglucosamine2-PA 243:273 mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA 243:319 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 4 26 theme human 659:663 arg1 component 679:687 the third component 669:687 the third component of human complement 669:707 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 4 26 theme human 659:663 arg1 C3 665:666 human C3 659:666 human C3 659:666 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 1 27 theme pyridylamino 138:149 arg1 derivatives 156:166 the pyridylamino (PA) derivatives 134:166 the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains 134:203 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 1 28 theme chains 198:203 arg1 derivatives 156:166 the pyridylamino (PA) derivatives 134:166 the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains 134:203 A mixture of the pyridylamino (PA) derivatives of 12 oligomannose-type sugar chains was fractionated into five fractions (mannose5N-acetylglucosamine2-PA approximately mannose9N-acetylglucosamine2-PA) by size-fractionation HPLC with a MicroPak AX-5 column. 3442327 4 29 theme third 673:677 arg1 component 679:687 the third component 669:687 the third component of human complement 669:707 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 4 29 theme third 673:677 arg1 C3 665:666 human C3 659:666 human C3 659:666 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 3442327 4 30 theme C3 665:666 arg1 chains 649:654 oligomannose-type sugar chains 625:654 oligomannose-type sugar chains of human C3, the third component of human complement 625:707 The method was used to identify the structures of oligomannose-type sugar chains of human C3, the third component of human complement. 11469797 2 0 theme various 588:594 arg1 levels 596:601 various levels 588:601 various levels of beta 1,4-GalT 588:618 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 2 1 theme ovary 486:490 arg1 cells 498:502 Chinese hamster ovary (CHO) cells 470:502 Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) 470:559 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 4 2 from branching 797:805 arg1 hIFN-gamma 826:835 hIFN-gamma 826:835 hIFN-gamma 826:835 The branching of sugar chains on hIFN-gamma was suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs. 11469797 2 3 theme human 514:518 arg1 -gamma 537:542 human interferon (hIFN)-gamma 514:542 human interferon (hIFN)-gamma (IM4/V/IV cells) 514:559 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 2 3 theme human 514:518 arg1 cells 554:558 IM4/V/IV cells 545:558 IM4/V/IV cells 545:558 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 2 4 theme hamster 478:484 arg1 cells 498:502 Chinese hamster ovary (CHO) cells 470:502 Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) 470:559 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 4 5 theme 1,4-GalT-enhanced 864:880 arg1 clones 882:887 the beta 1,4-GalT-enhanced clones 855:887 the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs 855:976 The branching of sugar chains on hIFN-gamma was suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs. 11469797 6 6 theme beta 1103:1106 arg1 1,4-GalT 1108:1115 beta 1,4-GalT 1103:1115 beta 1,4-GalT 1103:1115 The results showed that beta 1,4-GalT widely affects N-glycan processing by competing with GnT-IV, GnT-V, and alpha-mannosidase II in cells and also by some other mechanisms that suppress the conversion of high-mannose-type sugar chains to the hybrid type. 11469797 3 7 theme parental 662:669 arg1 cells 680:684 parental IM4/V/IV cells 662:684 parental IM4/V/IV cells 662:684 As we previously reported, parental IM4/V/IV cells express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily tetraantennary sugar chains. 11469797 6 8 theme high-mannose-type 1285:1301 arg1 chains 1309:1314 high-mannose-type sugar chains 1285:1314 high-mannose-type sugar chains 1285:1314 The results showed that beta 1,4-GalT widely affects N-glycan processing by competing with GnT-IV, GnT-V, and alpha-mannosidase II in cells and also by some other mechanisms that suppress the conversion of high-mannose-type sugar chains to the hybrid type. 11469797 4 9 theme beta 859:862 arg1 clones 882:887 the beta 1,4-GalT-enhanced clones 855:887 the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs 855:976 The branching of sugar chains on hIFN-gamma was suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs. 11469797 1 10 theme alpha1,6-d-mannoside 361:380 arg1 1,6-N-acetylglucosaminyltransferase 387:421 alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase 361:421 UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase 336:421 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 2 11 theme 1,4-GalT 611:618 arg1 levels 596:601 various levels 588:601 various levels of beta 1,4-GalT 588:618 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 4 12 theme chains 816:821 arg1 branching 797:805 The branching 793:805 The branching of sugar chains on hIFN-gamma 793:835 The branching of sugar chains on hIFN-gamma was suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs. 11469797 4 13 theme 1,4-GalT 952:959 arg1 activity 935:942 the intracellular activity 917:942 the intracellular activity of beta 1,4-GalT relative to GnTs 917:976 The branching of sugar chains on hIFN-gamma was suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs. 11469797 1 14 theme intracellular 199:211 arg1 competition 213:223 intracellular competition 199:223 intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase) 199:422 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 2 15 theme beta 606:609 arg1 1,4-GalT 611:618 beta 1,4-GalT 606:618 beta 1,4-GalT 606:618 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 4 16 theme beta 947:950 arg1 1,4-GalT 952:959 beta 1,4-GalT 947:959 beta 1,4-GalT relative to GnTs 947:976 The branching of sugar chains on hIFN-gamma was suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs. 11469797 1 17 theme competition 213:223 arg1 terms 190:194 terms 190:194 terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase) 190:422 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 0 18 theme widespread 4:13 arg1 effect 15:20 The widespread effect 0:20 The widespread effect of beta 0:28 The widespread effect of beta 1,4-galactosyltransferase on N-glycan processing. 11469797 1 19 theme beta 96:99 arg1 1,4-GalT 101:108 beta 1,4-GalT 96:108 beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase) 96:422 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 1 19 theme beta 96:99 arg1 UDP-galactose 111:123 UDP-galactose 111:123 UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase 111:184 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 2 20 theme IM4/V/IV 545:552 arg1 -gamma 537:542 human interferon (hIFN)-gamma 514:542 human interferon (hIFN)-gamma (IM4/V/IV cells) 514:559 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 2 20 theme IM4/V/IV 545:552 arg1 cells 554:558 IM4/V/IV cells 545:558 IM4/V/IV cells 545:558 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 1 21 theme beta 382:385 arg1 1,6-N-acetylglucosaminyltransferase 387:421 alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase 361:421 UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase 336:421 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 1 22 dep UDP-N-acetylglucosamine 336:358 arg1 1,6-N-acetylglucosaminyltransferase 387:421 alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase 361:421 UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase 336:421 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 2 23 theme 1,4-GalT-I 434:443 arg1 gene 445:448 The beta 1,4-GalT-I gene 425:448 The beta 1,4-GalT-I gene 425:448 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 2 24 theme beta 429:432 arg1 gene 445:448 The beta 1,4-GalT-I gene 425:448 The beta 1,4-GalT-I gene 425:448 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 4 25 theme intracellular 921:933 arg1 activity 935:942 the intracellular activity 917:942 the intracellular activity of beta 1,4-GalT relative to GnTs 917:976 The branching of sugar chains on hIFN-gamma was suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs. 11469797 3 26 theme IM4/V/IV 671:678 arg1 cells 680:684 parental IM4/V/IV cells 662:684 parental IM4/V/IV cells 662:684 As we previously reported, parental IM4/V/IV cells express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily tetraantennary sugar chains. 11469797 6 27 theme sugar 1303:1307 arg1 chains 1309:1314 high-mannose-type sugar chains 1285:1314 high-mannose-type sugar chains 1285:1314 The results showed that beta 1,4-GalT widely affects N-glycan processing by competing with GnT-IV, GnT-V, and alpha-mannosidase II in cells and also by some other mechanisms that suppress the conversion of high-mannose-type sugar chains to the hybrid type. 11469797 5 28 theme hybrid-type 1005:1015 arg1 chains 1045:1050 hybrid-type and high-mannose-type sugar chains 1005:1050 hybrid-type and high-mannose-type sugar chains 1005:1050 Moreover, the contents of hybrid-type and high-mannose-type sugar chains increased in these clones. 11469797 2 29 theme hIFN 532:535 arg1 -gamma 537:542 human interferon (hIFN)-gamma 514:542 human interferon (hIFN)-gamma (IM4/V/IV cells) 514:559 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 2 29 theme hIFN 532:535 arg1 cells 554:558 IM4/V/IV cells 545:558 IM4/V/IV cells 545:558 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 3 30 theme tetraantennary 764:777 arg1 chains 785:790 tetraantennary sugar chains 764:790 tetraantennary sugar chains 764:790 As we previously reported, parental IM4/V/IV cells express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily tetraantennary sugar chains. 11469797 3 31 theme high 694:697 arg1 levels 699:704 high levels 694:704 high levels of GnT-IVa and -V 694:722 As we previously reported, parental IM4/V/IV cells express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily tetraantennary sugar chains. 11469797 6 32 theme chains 1309:1314 arg1 conversion 1271:1280 the conversion 1267:1280 the conversion of high-mannose-type sugar chains to the hybrid type 1267:1333 The results showed that beta 1,4-GalT widely affects N-glycan processing by competing with GnT-IV, GnT-V, and alpha-mannosidase II in cells and also by some other mechanisms that suppress the conversion of high-mannose-type sugar chains to the hybrid type. 11469797 3 33 contain having 747:752 arg1 hIFN-gamma 736:745 hIFN-gamma 736:745 hIFN-gamma having primarily tetraantennary sugar chains 736:790 As we previously reported, parental IM4/V/IV cells express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily tetraantennary sugar chains. 11469797 3 33 contain having 747:752 arg2 chains 785:790 tetraantennary sugar chains 764:790 tetraantennary sugar chains 764:790 As we previously reported, parental IM4/V/IV cells express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily tetraantennary sugar chains. 11469797 0 34 theme beta 25:28 arg1 effect 15:20 The widespread effect 0:20 The widespread effect of beta 0:28 The widespread effect of beta 1,4-galactosyltransferase on N-glycan processing. 11469797 5 35 theme high-mannose-type 1021:1037 arg1 chains 1045:1050 hybrid-type and high-mannose-type sugar chains 1005:1050 hybrid-type and high-mannose-type sugar chains 1005:1050 Moreover, the contents of hybrid-type and high-mannose-type sugar chains increased in these clones. 11469797 1 36 theme alpha1,3-d-mannoside 263:282 arg1 beta1,4-N-acetylglucosaminyltransferase 284:322 alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase 263:322 UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase 238:322 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 0 37 theme N-glycan 59:66 arg1 processing 68:77 N-glycan processing 59:77 N-glycan processing 59:77 The widespread effect of beta 1,4-galactosyltransferase on N-glycan processing. 11469797 4 38 theme relative 961:968 arg1 1,4-GalT 952:959 beta 1,4-GalT 947:959 beta 1,4-GalT relative to GnTs 947:976 The branching of sugar chains on hIFN-gamma was suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs. 11469797 2 39 theme Chinese 470:476 arg1 cells 498:502 Chinese hamster ovary (CHO) cells 470:502 Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) 470:559 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 3 40 theme sugar 779:783 arg1 chains 785:790 tetraantennary sugar chains 764:790 tetraantennary sugar chains 764:790 As we previously reported, parental IM4/V/IV cells express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily tetraantennary sugar chains. 11469797 1 41 theme beta-d-N-acetylglucosaminide 126:153 arg1 1,4-galactosyltransferase 160:184 beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase 126:184 UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase 111:184 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 3 42 theme GnT-IVa 709:715 arg1 levels 699:704 high levels 694:704 high levels of GnT-IVa and -V 694:722 As we previously reported, parental IM4/V/IV cells express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily tetraantennary sugar chains. 11469797 6 43 theme hybrid 1323:1328 arg1 type 1330:1333 the hybrid type 1319:1333 the hybrid type 1319:1333 The results showed that beta 1,4-GalT widely affects N-glycan processing by competing with GnT-IV, GnT-V, and alpha-mannosidase II in cells and also by some other mechanisms that suppress the conversion of high-mannose-type sugar chains to the hybrid type. 11469797 1 44 theme beta 155:158 arg1 1,4-galactosyltransferase 160:184 beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase 126:184 UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase 111:184 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 1 45 with competition 213:223 arg1 UDP-N-acetylglucosamine 238:260 UDP-N-acetylglucosamine 238:260 UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase 238:322 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 1 45 with competition 213:223 arg1 GnT-IV 230:235 GnT-IV 230:235 GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) 230:323 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 1 45 with competition 213:223 arg1 GnT-V 329:333 GnT-V 329:333 GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase) 329:422 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 1 45 with competition 213:223 arg1 UDP-N-acetylglucosamine 336:358 UDP-N-acetylglucosamine 336:358 UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase 336:421 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 3 46 theme -V 721:722 arg1 levels 699:704 high levels 694:704 high levels of GnT-IVa and -V 694:722 As we previously reported, parental IM4/V/IV cells express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily tetraantennary sugar chains. 11469797 5 47 theme chains 1045:1050 arg1 contents 993:1000 the contents 989:1000 the contents of hybrid-type and high-mannose-type sugar chains 989:1050 Moreover, the contents of hybrid-type and high-mannose-type sugar chains increased in these clones. 11469797 6 48 theme other 1236:1240 arg1 mechanisms 1242:1251 some other mechanisms 1231:1251 some other mechanisms that suppress the conversion of high-mannose-type sugar chains to the hybrid type 1231:1333 The results showed that beta 1,4-GalT widely affects N-glycan processing by competing with GnT-IV, GnT-V, and alpha-mannosidase II in cells and also by some other mechanisms that suppress the conversion of high-mannose-type sugar chains to the hybrid type. 11469797 5 49 theme sugar 1039:1043 arg1 chains 1045:1050 hybrid-type and high-mannose-type sugar chains 1005:1050 hybrid-type and high-mannose-type sugar chains 1005:1050 Moreover, the contents of hybrid-type and high-mannose-type sugar chains increased in these clones. 11469797 2 50 theme interferon 520:529 arg1 -gamma 537:542 human interferon (hIFN)-gamma 514:542 human interferon (hIFN)-gamma (IM4/V/IV cells) 514:559 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 2 50 theme interferon 520:529 arg1 cells 554:558 IM4/V/IV cells 545:558 IM4/V/IV cells 545:558 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 2 51 theme CHO 493:495 arg1 cells 498:502 Chinese hamster ovary (CHO) cells 470:502 Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) 470:559 The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. 11469797 1 52 from 1,4-GalT 101:108 arg1 terms 190:194 terms 190:194 terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase) 190:422 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 6 53 theme N-glycan 1132:1139 arg1 processing 1141:1150 N-glycan processing 1132:1150 N-glycan processing 1132:1150 The results showed that beta 1,4-GalT widely affects N-glycan processing by competing with GnT-IV, GnT-V, and alpha-mannosidase II in cells and also by some other mechanisms that suppress the conversion of high-mannose-type sugar chains to the hybrid type. 11469797 1 54 dep UDP-N-acetylglucosamine 238:260 arg1 beta1,4-N-acetylglucosaminyltransferase 284:322 alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase 263:322 UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase 238:322 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 1 55 dep UDP-galactose 111:123 arg1 1,4-galactosyltransferase 160:184 beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase 126:184 UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase 111:184 We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). 11469797 4 56 theme sugar 810:814 arg1 chains 816:821 sugar chains 810:821 sugar chains 810:821 The branching of sugar chains on hIFN-gamma was suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs. 1527047 16 0 theme gastric 2068:2074 arg1 type 2076:2079 gastric type 2068:2079 gastric type 2068:2079 Collectively our findings suggest that Cl.16E colon cancer cells are able to synthesize mucin oligosaccharides of gastric type whose elongation is truncated by premature sialylation. 1527047 0 1 theme cancer 163:168 arg1 line 175:178 human colonic cancer cell line 149:178 the human colonic cancer cell line HT29 145:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 3 2 theme P-6 543:545 arg1 column 547:552 a Bio-gel P-6 column 533:552 a Bio-gel P-6 column 533:552 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 9 3 theme oligosaccharide 1421:1435 arg1 chains 1437:1442 oligosaccharide chains 1421:1442 oligosaccharide chains 1421:1442 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 4 4 theme oligosaccharides 892:907 arg1 weight 873:878 weight 873:878 weight of released oligosaccharides and four acidic fractions 873:933 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 10 5 theme predominant 1559:1569 arg1 hexasaccharide 1587:1600 a hexasaccharide 1585:1600 a hexasaccharide (fraction FII-4) 1585:1617 The predominant structure was a hexasaccharide (fraction FII-4). 1527047 10 5 theme predominant 1559:1569 arg1 structure 1571:1579 The predominant structure 1555:1579 The predominant structure 1555:1579 The predominant structure was a hexasaccharide (fraction FII-4). 1527047 0 6 theme line 175:178 arg1 derivative 131:140 a stably differentiated clonal derivative 100:140 a stably differentiated clonal derivative of the human colonic cancer cell line HT29 100:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 6 theme line 175:178 arg1 line 79:82 the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, 49:184 line 79:82 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 3 7 theme GalNAc 569:574 arg1 residues 576:583 GalNAc residues 569:583 GalNAc residues 569:583 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 6 8 theme NMR 1190:1192 arg1 spectroscopy 1194:1205 1H NMR spectroscopy 1187:1205 1H NMR spectroscopy 1187:1205 Structural determinations were carried out using methylation analysis, 1H NMR spectroscopy, and fast atom bombardment-mass spectrometry. 1527047 2 9 theme side 382:385 arg1 chains 387:392 Oligosaccharide side chains 366:392 Oligosaccharide side chains 366:392 Oligosaccharide side chains were isolated after beta-elimination. 1527047 11 10 theme colonic 1647:1653 arg1 mucins 1655:1660 normal colonic mucins 1640:1660 normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol 1640:1873 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 16 11 theme colon 2000:2004 arg1 cells 2013:2017 Cl.16E colon cancer cells 1993:2017 Cl.16E colon cancer cells 1993:2017 Collectively our findings suggest that Cl.16E colon cancer cells are able to synthesize mucin oligosaccharides of gastric type whose elongation is truncated by premature sialylation. 1527047 9 12 from linkage 1499:1505 arg1 addition 1462:1469 addition 1462:1469 addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues 1462:1552 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 6 13 theme methylation 1165:1175 arg1 analysis 1177:1184 methylation analysis 1165:1184 methylation analysis 1165:1184 Structural determinations were carried out using methylation analysis, 1H NMR spectroscopy, and fast atom bombardment-mass spectrometry. 1527047 5 14 theme alditols 1082:1089 arg1 % 1055:1055 78% 1053:1055 78% of total oligosaccharide alditols 1053:1089 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 5 14 theme alditols 1082:1089 arg1 alditols 1082:1089 total oligosaccharide alditols 1060:1089 total oligosaccharide alditols 1060:1089 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 9 15 theme acid 1481:1484 arg1 addition 1462:1469 addition 1462:1469 addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues 1462:1552 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 3 16 from preparation 685:695 arg1 absent 669:674 absent 669:674 absent 669:674 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 11 17 theme beta 1793:1796 arg1 1-3R 1798:1801 Gal beta 1-3R 1789:1801 Gal beta 1-3R 1789:1801 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 0 18 theme clonal 124:129 arg1 derivative 131:140 a stably differentiated clonal derivative 100:140 a stably differentiated clonal derivative of the human colonic cancer cell line HT29 100:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 18 theme clonal 124:129 arg1 line 79:82 the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, 49:184 line 79:82 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 1 19 from centrifugation 342:355 arg1 CsCl 360:363 CsCl 360:363 CsCl 360:363 Secretory mucins were purified by equilibrium density gradient centrifugation in CsCl. 1527047 0 20 theme colonic 263:269 arg1 cancer 271:276 colonic cancer 263:276 colonic cancer 263:276 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 9 21 theme alpha 1489:1493 arg1 linkage 1499:1505 alpha 2-3 linkage 1489:1505 alpha 2-3 linkage 1489:1505 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 10 22 theme fraction 1603:1610 arg1 hexasaccharide 1587:1600 a hexasaccharide 1585:1600 a hexasaccharide (fraction FII-4) 1585:1617 The predominant structure was a hexasaccharide (fraction FII-4). 1527047 10 22 theme fraction 1603:1610 arg1 FII-4 1612:1616 fraction FII-4 1603:1616 fraction FII-4 1603:1616 The predominant structure was a hexasaccharide (fraction FII-4). 1527047 13 23 dep 260 1882:1884 arg1 D.K. 1908:1911 D.K. 1908:1911 D.K. 1908:1911 260, 8262-8271; Podolsky, D.K. (1985) J. Biol. 1527047 4 24 theme fractions 925:933 arg1 weight 873:878 weight 873:878 weight of released oligosaccharides and four acidic fractions 873:933 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 6 25 theme bombardment-mass 1222:1237 arg1 spectrometry 1239:1250 fast atom bombardment-mass spectrometry 1212:1250 fast atom bombardment-mass spectrometry 1212:1250 Structural determinations were carried out using methylation analysis, 1H NMR spectroscopy, and fast atom bombardment-mass spectrometry. 1527047 4 26 theme high 741:744 arg1 chromatography 765:778 high performance liquid chromatography 741:778 high performance liquid chromatography (HPLC) 741:785 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 4 26 theme high 741:744 arg1 HPLC 781:784 HPLC 781:784 HPLC 781:784 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 0 27 theme human 149:153 arg1 line 175:178 human colonic cancer cell line 149:178 the human colonic cancer cell line HT29 145:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 5 28 theme total 1060:1064 arg1 alditols 1082:1089 total oligosaccharide alditols 1060:1089 total oligosaccharide alditols 1060:1089 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 9 29 theme Gal 1510:1512 arg1 1-3R 1519:1522 Gal beta 1-3R 1510:1522 Gal beta 1-3R 1510:1522 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 6 30 theme fast 1212:1215 arg1 spectrometry 1239:1250 fast atom bombardment-mass spectrometry 1212:1250 fast atom bombardment-mass spectrometry 1212:1250 Structural determinations were carried out using methylation analysis, 1H NMR spectroscopy, and fast atom bombardment-mass spectrometry. 1527047 5 31 dep FI 965:966 arg1 encompassing 976:987 encompassing 976:987 encompassing mono- and disialylated structures, respectively 976:1035 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 5 31 dep FI 965:966 arg1 containing 1042:1051 containing 1042:1051 containing 78% of total oligosaccharide alditols 1042:1089 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 3 32 dep absent 669:674 arg1 2 650:650 2 650:650 2 650:650 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 0 33 from chains 243:248 arg1 cancer 271:276 colonic cancer 263:276 colonic cancer 263:276 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 34 theme cell 74:77 arg1 line 79:82 the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, 49:184 line 79:82 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 34 theme cell 74:77 arg1 derivative 131:140 a stably differentiated clonal derivative 100:140 a stably differentiated clonal derivative of the human colonic cancer cell line HT29 100:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 1 35 theme density 325:331 arg1 centrifugation 342:355 equilibrium density gradient centrifugation 313:355 equilibrium density gradient centrifugation in CsCl 313:363 Secretory mucins were purified by equilibrium density gradient centrifugation in CsCl. 1527047 11 36 theme sialic 1750:1755 arg1 acids 1757:1761 sialic acids 1750:1761 sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R 1750:1842 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 9 37 theme beta 1535:1538 arg1 residues 1545:1552 Gal beta 1-4R residues 1531:1552 Gal beta 1-4R residues 1531:1552 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 4 38 theme quaternary 790:799 arg1 packings 807:814 quaternary amine packings 790:814 quaternary amine packings 790:814 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 0 39 theme chains 243:248 arg1 structure 214:222 the structure 210:222 the structure of oligosaccharide chains of mucins in colonic cancer 210:276 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 16 40 theme Cl.16E 1993:1998 arg1 cells 2013:2017 Cl.16E colon cancer cells 1993:2017 Cl.16E colon cancer cells 1993:2017 Collectively our findings suggest that Cl.16E colon cancer cells are able to synthesize mucin oligosaccharides of gastric type whose elongation is truncated by premature sialylation. 1527047 4 41 theme liquid 758:763 arg1 chromatography 765:778 high performance liquid chromatography 741:778 high performance liquid chromatography (HPLC) 741:785 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 4 41 theme liquid 758:763 arg1 HPLC 781:784 HPLC 781:784 HPLC 781:784 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 3 42 theme Compositional 432:444 arg1 analysis 446:453 Compositional analysis 432:453 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column 432:552 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 0 43 theme Oligosaccharide 0:14 arg1 structures 16:25 Oligosaccharide structures 0:25 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, 0:184 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 44 theme mucins 253:258 arg1 chains 243:248 oligosaccharide chains 227:248 oligosaccharide chains of mucins in colonic cancer 227:276 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 3 45 dep showed 554:559 arg1 absent 669:674 absent 669:674 absent 669:674 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 3 45 dep showed 554:559 arg1 located 590:596 located 590:596 located 590:596 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 0 46 from mucins 253:258 arg1 cancer 271:276 colonic cancer 263:276 colonic cancer 263:276 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 47 theme colonic 59:65 arg1 line 79:82 the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, 49:184 line 79:82 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 47 theme colonic 59:65 arg1 derivative 131:140 a stably differentiated clonal derivative 100:140 a stably differentiated clonal derivative of the human colonic cancer cell line HT29 100:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 4 48 theme neutral 829:835 arg1 fraction 837:844 a minor neutral fraction 821:844 a minor neutral fraction representing about 6.5% 821:868 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 3 49 from ends 626:629 arg1 located 590:596 located 590:596 located 590:596 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 0 50 used used 190:193 arg2 structures 16:25 Oligosaccharide structures 0:25 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, 0:184 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 1 51 theme Secretory 279:287 arg1 mucins 289:294 Secretory mucins 279:294 Secretory mucins 279:294 Secretory mucins were purified by equilibrium density gradient centrifugation in CsCl. 1527047 7 52 theme oligosaccharide 1260:1274 arg1 structures 1276:1285 Twelve oligosaccharide structures 1253:1285 Twelve oligosaccharide structures 1253:1285 Twelve oligosaccharide structures were determined which ranged in size from 3 to 8 residues. 1527047 11 53 theme Gal 1807:1809 arg1 1-4R 1816:1819 Gal beta 1-4R 1807:1819 Gal beta 1-4R 1807:1819 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 15 54 dep 260 1935:1937 arg1 15510-15515 1940:1950 15510-15515 1940:1950 15510-15515 1940:1950 260, 15510-15515). 1527047 13 55 dep Biol 1923:1926 arg1 1985 1914:1917 1985 1914:1917 1985 1914:1917 260, 8262-8271; Podolsky, D.K. (1985) J. Biol. 1527047 13 55 dep Biol 1923:1926 arg1 260 1882:1884 260 1882:1884 260 1882:1884 260, 8262-8271; Podolsky, D.K. (1985) J. Biol. 1527047 11 56 theme core 1722:1725 arg1 structures 1729:1738 core 3 structures 1722:1738 core 3 structures 1722:1738 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 3 57 theme gel 515:517 arg1 filtration 519:528 gel filtration 515:528 gel filtration on a Bio-gel P-6 column 515:552 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 11 58 dep D.K. 1855:1858 arg1 Biol 1870:1873 Biol 1870:1873 Biol 1870:1873 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 9 59 from addition 1462:1469 arg1 linkage 1499:1505 alpha 2-3 linkage 1489:1505 alpha 2-3 linkage 1489:1505 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 11 60 dep found 1701:1705 arg1 D.K. 1855:1858 D.K. 1855:1858 D.K. 1855:1858 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 11 60 dep found 1701:1705 arg1 1985 1861:1864 1985 1861:1864 1985 1861:1864 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 16 61 theme type 2076:2079 arg1 oligosaccharides 2048:2063 mucin oligosaccharides 2042:2063 mucin oligosaccharides of gastric type whose elongation is truncated by premature sialylation 2042:2134 Collectively our findings suggest that Cl.16E colon cancer cells are able to synthesize mucin oligosaccharides of gastric type whose elongation is truncated by premature sialylation. 1527047 11 62 theme normal 1640:1645 arg1 mucins 1655:1660 normal colonic mucins 1640:1660 normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol 1640:1873 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 0 63 theme cell 170:173 arg1 line 175:178 human colonic cancer cell line 149:178 the human colonic cancer cell line HT29 145:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 3 64 theme Bio-gel 535:541 arg1 column 547:552 a Bio-gel P-6 column 533:552 a Bio-gel P-6 column 533:552 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 9 65 theme chains 1437:1442 arg1 Elongation 1407:1416 Elongation 1407:1416 Elongation of oligosaccharide chains 1407:1442 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 4 66 theme released 883:890 arg1 oligosaccharides 892:907 released oligosaccharides 883:907 released oligosaccharides 883:907 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 6 67 theme 1H 1187:1188 arg1 spectroscopy 1194:1205 1H NMR spectroscopy 1187:1205 1H NMR spectroscopy 1187:1205 Structural determinations were carried out using methylation analysis, 1H NMR spectroscopy, and fast atom bombardment-mass spectrometry. 1527047 0 68 from cancer 271:276 arg1 chains 243:248 oligosaccharide chains 227:248 oligosaccharide chains of mucins in colonic cancer 227:276 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 16 69 theme cancer 2006:2011 arg1 cells 2013:2017 Cl.16E colon cancer cells 1993:2017 Cl.16E colon cancer cells 1993:2017 Collectively our findings suggest that Cl.16E colon cancer cells are able to synthesize mucin oligosaccharides of gastric type whose elongation is truncated by premature sialylation. 1527047 3 70 from filtration 519:528 arg1 column 547:552 a Bio-gel P-6 column 533:552 a Bio-gel P-6 column 533:552 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 11 71 contain carry 1744:1748 arg2 acids 1757:1761 sialic acids 1750:1761 sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R 1750:1842 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 11 71 contain carry 1744:1748 arg1 oligosaccharides 1668:1683 oligosaccharides 1668:1683 oligosaccharides 1668:1683 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 0 72 theme differentiated 109:122 arg1 derivative 131:140 a stably differentiated clonal derivative 100:140 a stably differentiated clonal derivative of the human colonic cancer cell line HT29 100:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 72 theme differentiated 109:122 arg1 line 79:82 the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, 49:184 line 79:82 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 9 73 theme sialic 1474:1479 arg1 acid 1481:1484 sialic acid 1474:1484 sialic acid in alpha 2-3 linkage 1474:1505 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 11 74 from acids 1757:1761 arg1 linkage 1778:1784 alpha (2-6) linkage 1766:1784 alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R 1766:1842 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 3 75 theme reducing 617:624 arg1 ends 626:629 the reducing ends 613:629 the reducing ends of the chains 613:643 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 16 76 theme mucin 2042:2046 arg1 oligosaccharides 2048:2063 mucin oligosaccharides 2042:2063 mucin oligosaccharides of gastric type whose elongation is truncated by premature sialylation 2042:2134 Collectively our findings suggest that Cl.16E colon cancer cells are able to synthesize mucin oligosaccharides of gastric type whose elongation is truncated by premature sialylation. 1527047 9 77 theme 2-3 1495:1497 arg1 linkage 1499:1505 alpha 2-3 linkage 1489:1505 alpha 2-3 linkage 1489:1505 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 11 78 theme Gal 1789:1791 arg1 1-3R 1798:1801 Gal beta 1-3R 1789:1801 Gal beta 1-3R 1789:1801 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 0 79 theme colonic 155:161 arg1 line 175:178 human colonic cancer cell line 149:178 the human colonic cancer cell line HT29 145:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 3 80 theme chains 638:643 arg1 ends 626:629 the reducing ends 613:629 the reducing ends of the chains 613:643 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 5 81 theme acidic 940:945 arg1 FI 965:966 FI 965:966 FI 965:966 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 5 81 theme acidic 940:945 arg1 FII 972:974 FII 972:974 FII 972:974 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 5 81 theme acidic 940:945 arg1 fractions 947:955 Two acidic fractions 936:955 Two acidic fractions 936:955 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 4 82 theme acidic 918:923 arg1 fractions 925:933 four acidic fractions 913:933 four acidic fractions 913:933 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 6 83 theme atom 1217:1220 arg1 spectrometry 1239:1250 fast atom bombardment-mass spectrometry 1212:1250 fast atom bombardment-mass spectrometry 1212:1250 Structural determinations were carried out using methylation analysis, 1H NMR spectroscopy, and fast atom bombardment-mass spectrometry. 1527047 0 84 theme cancer 67:72 arg1 line 79:82 the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, 49:184 line 79:82 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 84 theme cancer 67:72 arg1 derivative 131:140 a stably differentiated clonal derivative 100:140 a stably differentiated clonal derivative of the human colonic cancer cell line HT29 100:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 5 85 theme oligosaccharide 1066:1080 arg1 alditols 1082:1089 total oligosaccharide alditols 1060:1089 total oligosaccharide alditols 1060:1089 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 9 86 theme beta 1514:1517 arg1 1-3R 1519:1522 Gal beta 1-3R 1510:1522 Gal beta 1-3R 1510:1522 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 1 87 theme equilibrium 313:323 arg1 centrifugation 342:355 equilibrium density gradient centrifugation 313:355 equilibrium density gradient centrifugation in CsCl 313:363 Secretory mucins were purified by equilibrium density gradient centrifugation in CsCl. 1527047 3 88 dep located 590:596 arg1 1 561:561 1 561:561 1 561:561 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 11 89 theme alpha 1766:1770 arg1 linkage 1778:1784 alpha (2-6) linkage 1766:1784 alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R 1766:1842 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 1 90 theme gradient 333:340 arg1 centrifugation 342:355 equilibrium density gradient centrifugation 313:355 equilibrium density gradient centrifugation in CsCl 313:363 Secretory mucins were purified by equilibrium density gradient centrifugation in CsCl. 1527047 9 91 theme Gal 1531:1533 arg1 residues 1545:1552 Gal beta 1-4R residues 1531:1552 Gal beta 1-4R residues 1531:1552 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 16 92 theme premature 2114:2122 arg1 sialylation 2124:2134 premature sialylation 2114:2134 premature sialylation 2114:2134 Collectively our findings suggest that Cl.16E colon cancer cells are able to synthesize mucin oligosaccharides of gastric type whose elongation is truncated by premature sialylation. 1527047 0 93 dep line 175:178 arg1 HT29 180:183 HT29 180:183 the human colonic cancer cell line HT29 145:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 9 94 theme 1-4R 1540:1543 arg1 residues 1545:1552 Gal beta 1-4R residues 1531:1552 Gal beta 1-4R residues 1531:1552 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 8 95 theme core 1383:1386 arg1 types 1388:1392 core types 1383:1392 core types 1, 2, and 4 1383:1404 These oligosaccharides were based on core types 1, 2, and 4. 1527047 3 96 theme oligosaccharide-alditols 458:481 arg1 analysis 446:453 Compositional analysis 432:453 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column 432:552 Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. 1527047 11 97 theme GalNAc 1829:1834 arg1 alpha-R 1836:1842 GalNAc alpha-R 1829:1842 GalNAc alpha-R 1829:1842 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 0 98 theme oligosaccharide 227:241 arg1 chains 243:248 oligosaccharide chains 227:248 oligosaccharide chains of mucins in colonic cancer 227:276 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 99 dep line 79:82 arg1 Cl.16E 92:97 Cl.16E 92:97 Cl.16E 92:97 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 4 100 theme performance 746:756 arg1 chromatography 765:778 high performance liquid chromatography 741:778 high performance liquid chromatography (HPLC) 741:785 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 4 100 theme performance 746:756 arg1 HPLC 781:784 HPLC 781:784 HPLC 781:784 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 2 101 theme Oligosaccharide 366:380 arg1 chains 387:392 Oligosaccharide side chains 366:392 Oligosaccharide side chains 366:392 Oligosaccharide side chains were isolated after beta-elimination. 1527047 0 102 theme mucins 30:35 arg1 structures 16:25 Oligosaccharide structures 0:25 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, 0:184 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 5 103 theme mono- 989:993 arg1 structures 1012:1021 mono- and disialylated structures 989:1021 mono- and disialylated structures 989:1021 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 5 104 gly disialylated 999:1010 arg1 structures 1012:1021 mono- and disialylated structures 989:1021 mono- and disialylated structures 989:1021 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 4 105 theme minor 823:827 arg1 fraction 837:844 a minor neutral fraction 821:844 a minor neutral fraction representing about 6.5% 821:868 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 0 106 theme human 53:57 arg1 line 79:82 the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, 49:184 line 79:82 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 0 106 theme human 53:57 arg1 derivative 131:140 a stably differentiated clonal derivative 100:140 a stably differentiated clonal derivative of the human colonic cancer cell line HT29 100:183 Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. 1527047 11 107 theme beta 1811:1814 arg1 1-4R 1816:1819 Gal beta 1-4R 1807:1819 Gal beta 1-4R 1807:1819 This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. 1527047 5 108 theme disialylated 999:1010 arg1 structures 1012:1021 mono- and disialylated structures 989:1021 mono- and disialylated structures 989:1021 Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. 1527047 9 109 from acid 1481:1484 arg1 linkage 1499:1505 alpha 2-3 linkage 1489:1505 alpha 2-3 linkage 1489:1505 Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. 1527047 4 110 theme amine 801:805 arg1 packings 807:814 quaternary amine packings 790:814 quaternary amine packings 790:814 Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. 1527047 7 111 dep 8 1334:1334 arg1 to 1331:1332 to 1331:1332 to 1331:1332 Twelve oligosaccharide structures were determined which ranged in size from 3 to 8 residues. 1527047 6 112 theme Structural 1116:1125 arg1 determinations 1127:1140 Structural determinations 1116:1140 Structural determinations 1116:1140 Structural determinations were carried out using methylation analysis, 1H NMR spectroscopy, and fast atom bombardment-mass spectrometry. 7774715 4 0 theme identified 473:482 arg1 structures 484:493 The identified structures 469:493 The identified structures 469:493 The identified structures corresponded to N-acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. 7774715 5 1 gly alpha-1,6-fucosylated 673:693 arg2 residue 709:715 the GlcNAc residue 698:715 the GlcNAc residue linked to asparagine 698:736 Moreover, 70% of total glycans were alpha-1,6-fucosylated at the GlcNAc residue linked to asparagine. 7774715 5 1 gly alpha-1,6-fucosylated 673:693 arg1 % 649:649 70% 647:649 70% of total glycans 647:666 Moreover, 70% of total glycans were alpha-1,6-fucosylated at the GlcNAc residue linked to asparagine. 7774715 5 1 gly alpha-1,6-fucosylated 673:693 arg1 glycans 660:666 total glycans 654:666 total glycans 654:666 Moreover, 70% of total glycans were alpha-1,6-fucosylated at the GlcNAc residue linked to asparagine. 7774715 6 2 dep in 951:952 arg1 vitro 954:958 vitro 954:958 vitro 954:958 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 4 3 gly alpha-2,3-monosialylated 599:622 arg1 forms 630:634 alpha-2,3-monosialylated (20%) forms 599:634 alpha-2,3-monosialylated (20%) forms 599:634 The identified structures corresponded to N-acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. 7774715 1 4 theme BHK 252:254 arg1 cells 256:260 BHK cells 252:260 BHK cells 252:260 A full-length cDNA coding for human lactoferrin was isolated from a mammary gland library and the recombinant protein was expressed in BHK cells as described by Stowell K. M. et al. [1991, Biochem. 7774715 0 5 theme BHK 106:108 arg1 cells 110:114 BHK cells 106:114 BHK cells 106:114 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin expressed in BHK cells. 7774715 3 6 from lactoferrin 380:390 arg1 glycans 346:352 Two N-linked glycans 333:352 Two N-linked glycans from purified recombinant lactoferrin 333:390 Two N-linked glycans from purified recombinant lactoferrin were released by hydrazinolysis and analyzed by 400-MHz 1H-NMR spectroscopy. 7774715 6 7 theme biological 960:969 arg1 studies 971:977 in vivo and in vitro biological studies 939:977 in vivo and in vitro biological studies 939:977 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 8 theme glycan 756:761 arg1 moiety 763:768 its glycan moiety 752:768 its glycan moiety 752:768 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 9 theme structural 875:884 arg1 features 886:893 specific structural features 866:893 specific structural features which should be taken into account prior to in vivo and in vitro biological studies 866:977 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 10 theme recombinant 775:785 arg1 lactoferrins 819:830 native lactoferrins 812:830 native lactoferrins from milk or leucocytes 812:854 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 10 theme recombinant 775:785 arg1 glycoprotein 787:798 the recombinant glycoprotein 771:798 the recombinant glycoprotein 771:798 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 11 from lactoferrins 819:830 arg1 regard 742:747 regard 742:747 regard to its glycan moiety 742:768 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 1 12 dep M. 289:290 arg1 [1991 299:303 [1991 299:303 [1991 299:303 A full-length cDNA coding for human lactoferrin was isolated from a mammary gland library and the recombinant protein was expressed in BHK cells as described by Stowell K. M. et al. [1991, Biochem. 7774715 3 13 theme recombinant 368:378 arg1 lactoferrin 380:390 purified recombinant lactoferrin 359:390 purified recombinant lactoferrin 359:390 Two N-linked glycans from purified recombinant lactoferrin were released by hydrazinolysis and analyzed by 400-MHz 1H-NMR spectroscopy. 7774715 6 14 from milk 837:840 arg1 lactoferrins 819:830 native lactoferrins 812:830 native lactoferrins from milk or leucocytes 812:854 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 14 from milk 837:840 arg1 glycoprotein 787:798 the recombinant glycoprotein 771:798 the recombinant glycoprotein 771:798 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 3 15 theme N-linked 337:344 arg1 glycans 346:352 Two N-linked glycans 333:352 Two N-linked glycans from purified recombinant lactoferrin 333:390 Two N-linked glycans from purified recombinant lactoferrin were released by hydrazinolysis and analyzed by 400-MHz 1H-NMR spectroscopy. 7774715 6 16 theme in 939:940 arg1 studies 971:977 in vivo and in vitro biological studies 939:977 in vivo and in vitro biological studies 939:977 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 17 theme in 951:952 arg1 studies 971:977 in vivo and in vitro biological studies 939:977 in vivo and in vitro biological studies 939:977 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 0 18 theme Structural 0:9 arg1 determination 11:23 Structural determination 0:23 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin 0:91 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin expressed in BHK cells. 7774715 4 19 theme alpha-2,3-disialylated 561:582 arg1 forms 584:588 alpha-2,3-disialylated forms 561:588 alpha-2,3-disialylated forms (80%) 561:594 The identified structures corresponded to N-acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. 7774715 4 19 theme alpha-2,3-disialylated 561:582 arg1 % 593:593 80% 591:593 80% 591:593 The identified structures corresponded to N-acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. 7774715 0 20 attach isolated 49:56 arg1 lactoferrin 81:91 recombinant human lactoferrin 63:91 recombinant human lactoferrin 63:91 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin expressed in BHK cells. 7774715 0 20 attach isolated 49:56 arg2 glycans 41:47 two N-linked glycans 28:47 two N-linked glycans isolated from recombinant human lactoferrin 28:91 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin expressed in BHK cells. 7774715 1 21 theme mammary 185:191 arg1 library 199:205 a mammary gland library 183:205 a mammary gland library 183:205 A full-length cDNA coding for human lactoferrin was isolated from a mammary gland library and the recombinant protein was expressed in BHK cells as described by Stowell K. M. et al. [1991, Biochem. 7774715 0 22 link N-linked 32:39 arg1 glycans 41:47 two N-linked glycans 28:47 two N-linked glycans isolated from recombinant human lactoferrin 28:91 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin expressed in BHK cells. 7774715 1 23 theme gland 193:197 arg1 library 199:205 a mammary gland library 183:205 a mammary gland library 183:205 A full-length cDNA coding for human lactoferrin was isolated from a mammary gland library and the recombinant protein was expressed in BHK cells as described by Stowell K. M. et al. [1991, Biochem. 7774715 6 24 from leucocytes 845:854 arg1 lactoferrins 819:830 native lactoferrins 812:830 native lactoferrins from milk or leucocytes 812:854 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 24 from leucocytes 845:854 arg1 glycoprotein 787:798 the recombinant glycoprotein 771:798 the recombinant glycoprotein 771:798 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 3 25 theme 400-MHz 440:446 arg1 spectroscopy 455:466 400-MHz 1H-NMR spectroscopy 440:466 400-MHz 1H-NMR spectroscopy 440:466 Two N-linked glycans from purified recombinant lactoferrin were released by hydrazinolysis and analyzed by 400-MHz 1H-NMR spectroscopy. 7774715 0 26 theme glycans 41:47 arg1 determination 11:23 Structural determination 0:23 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin 0:91 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin expressed in BHK cells. 7774715 6 27 theme specific 866:873 arg1 features 886:893 specific structural features 866:893 specific structural features which should be taken into account prior to in vivo and in vitro biological studies 866:977 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 5 28 theme GlcNAc 702:707 arg1 residue 709:715 the GlcNAc residue 698:715 the GlcNAc residue linked to asparagine 698:736 Moreover, 70% of total glycans were alpha-1,6-fucosylated at the GlcNAc residue linked to asparagine. 7774715 1 29 attach isolated 169:176 arg1 library 199:205 a mammary gland library 183:205 a mammary gland library 183:205 A full-length cDNA coding for human lactoferrin was isolated from a mammary gland library and the recombinant protein was expressed in BHK cells as described by Stowell K. M. et al. [1991, Biochem. 7774715 1 29 attach isolated 169:176 arg2 cDNA 131:134 A full-length cDNA 117:134 A full-length cDNA coding for human lactoferrin 117:163 A full-length cDNA coding for human lactoferrin was isolated from a mammary gland library and the recombinant protein was expressed in BHK cells as described by Stowell K. M. et al. [1991, Biochem. 7774715 0 30 theme N-linked 32:39 arg1 glycans 41:47 two N-linked glycans 28:47 two N-linked glycans isolated from recombinant human lactoferrin 28:91 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin expressed in BHK cells. 7774715 4 31 theme biantennary 532:542 arg1 glycans 544:550 N-acetyllactosaminic biantennary glycans 511:550 N-acetyllactosaminic biantennary glycans 511:550 The identified structures corresponded to N-acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. 7774715 4 32 theme N-acetyllactosaminic 511:530 arg1 glycans 544:550 N-acetyllactosaminic biantennary glycans 511:550 N-acetyllactosaminic biantennary glycans 511:550 The identified structures corresponded to N-acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. 7774715 5 33 theme total 654:658 arg1 glycans 660:666 total glycans 654:666 total glycans 654:666 Moreover, 70% of total glycans were alpha-1,6-fucosylated at the GlcNAc residue linked to asparagine. 7774715 4 34 gly alpha-2,3-disialylated 561:582 arg1 forms 584:588 alpha-2,3-disialylated forms 561:588 alpha-2,3-disialylated forms (80%) 561:594 The identified structures corresponded to N-acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. 7774715 4 34 gly alpha-2,3-disialylated 561:582 arg1 % 593:593 80% 591:593 80% 591:593 The identified structures corresponded to N-acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. 7774715 3 35 theme purified 359:366 arg1 lactoferrin 380:390 purified recombinant lactoferrin 359:390 purified recombinant lactoferrin 359:390 Two N-linked glycans from purified recombinant lactoferrin were released by hydrazinolysis and analyzed by 400-MHz 1H-NMR spectroscopy. 7774715 5 36 theme glycans 660:666 arg1 % 649:649 70% 647:649 70% of total glycans 647:666 Moreover, 70% of total glycans were alpha-1,6-fucosylated at the GlcNAc residue linked to asparagine. 7774715 5 36 theme glycans 660:666 arg1 glycans 660:666 total glycans 654:666 total glycans 654:666 Moreover, 70% of total glycans were alpha-1,6-fucosylated at the GlcNAc residue linked to asparagine. 7774715 1 37 theme full-length 119:129 arg1 cDNA 131:134 A full-length cDNA 117:134 A full-length cDNA coding for human lactoferrin 117:163 A full-length cDNA coding for human lactoferrin was isolated from a mammary gland library and the recombinant protein was expressed in BHK cells as described by Stowell K. M. et al. [1991, Biochem. 7774715 6 38 gly glycoprotein 787:798 arg1 lactoferrins 819:830 native lactoferrins 812:830 native lactoferrins from milk or leucocytes 812:854 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 38 gly glycoprotein 787:798 arg1 glycoprotein 787:798 the recombinant glycoprotein 771:798 the recombinant glycoprotein 771:798 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 39 dep in 939:940 arg1 vivo 942:945 vivo 942:945 vivo 942:945 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 3 40 theme 1H-NMR 448:453 arg1 spectroscopy 455:466 400-MHz 1H-NMR spectroscopy 440:466 400-MHz 1H-NMR spectroscopy 440:466 Two N-linked glycans from purified recombinant lactoferrin were released by hydrazinolysis and analyzed by 400-MHz 1H-NMR spectroscopy. 7774715 1 41 theme recombinant 215:225 arg1 protein 227:233 the recombinant protein 211:233 the recombinant protein 211:233 A full-length cDNA coding for human lactoferrin was isolated from a mammary gland library and the recombinant protein was expressed in BHK cells as described by Stowell K. M. et al. [1991, Biochem. 7774715 6 42 theme native 812:817 arg1 lactoferrins 819:830 native lactoferrins 812:830 native lactoferrins from milk or leucocytes 812:854 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 6 42 theme native 812:817 arg1 glycoprotein 787:798 the recombinant glycoprotein 771:798 the recombinant glycoprotein 771:798 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 7774715 4 43 theme alpha-2,3-monosialylated 599:622 arg1 forms 630:634 alpha-2,3-monosialylated (20%) forms 599:634 alpha-2,3-monosialylated (20%) forms 599:634 The identified structures corresponded to N-acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. 7774715 0 44 theme human 75:79 arg1 lactoferrin 81:91 recombinant human lactoferrin 63:91 recombinant human lactoferrin 63:91 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin expressed in BHK cells. 7774715 4 45 dep alpha-2,3-monosialylated 599:622 arg1 % 627:627 20% 625:627 20% 625:627 The identified structures corresponded to N-acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. 7774715 3 46 link N-linked 337:344 arg1 glycans 346:352 Two N-linked glycans 333:352 Two N-linked glycans from purified recombinant lactoferrin 333:390 Two N-linked glycans from purified recombinant lactoferrin were released by hydrazinolysis and analyzed by 400-MHz 1H-NMR spectroscopy. 7774715 5 47 attach linked 717:722 arg2 residue 709:715 the GlcNAc residue 698:715 the GlcNAc residue linked to asparagine 698:736 Moreover, 70% of total glycans were alpha-1,6-fucosylated at the GlcNAc residue linked to asparagine. 7774715 5 47 attach linked 717:722 arg1 asparagine 727:736 asparagine 727:736 asparagine 727:736 Moreover, 70% of total glycans were alpha-1,6-fucosylated at the GlcNAc residue linked to asparagine. 7774715 0 48 theme recombinant 63:73 arg1 lactoferrin 81:91 recombinant human lactoferrin 63:91 recombinant human lactoferrin 63:91 Structural determination of two N-linked glycans isolated from recombinant human lactoferrin expressed in BHK cells. 7774715 1 49 theme human 147:151 arg1 lactoferrin 153:163 human lactoferrin 147:163 human lactoferrin 147:163 A full-length cDNA coding for human lactoferrin was isolated from a mammary gland library and the recombinant protein was expressed in BHK cells as described by Stowell K. M. et al. [1991, Biochem. 7774715 6 50 theme prior 930:934 arg1 account 922:928 account 922:928 account prior to in vivo and in vitro biological studies 922:977 In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. 2136357 0 0 theme Tamm-Horsfall 94:106 arg1 uromodulin 82:91 human and bovine uromodulin 65:91 human and bovine uromodulin (Tamm-Horsfall glycoprotein) 65:120 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 0 0 theme Tamm-Horsfall 94:106 arg1 glycoprotein 108:119 Tamm-Horsfall glycoprotein 94:119 Tamm-Horsfall glycoprotein 94:119 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 5 1 dep species 1486:1492 arg1 human 1495:1499 human 1495:1499 human 1495:1499 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 2 2 theme antigen-specific 575:590 arg1 proliferation 599:611 antigen-specific T cell proliferation 575:611 antigen-specific T cell proliferation 575:611 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 5 3 theme nonpregnant 1456:1466 arg1 samples 1468:1474 pregnant vs. nonpregnant samples 1443:1474 pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1443:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 0 4 from changes 21:27 arg1 oligosaccharides 45:60 oligomannose oligosaccharides 32:60 oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein) 32:120 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 3 5 theme oligomannose 995:1006 arg1 profile 1008:1014 the oligomannose profile 991:1014 the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) 991:1058 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 2 6 theme 0.2-2 623:627 arg1 microM 629:634 0.2-2 microM 623:634 0.2-2 microM 623:634 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 5 7 theme chains 1433:1438 arg1 proportion 1396:1405 a significantly greater proportion 1372:1405 a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1372:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 5 8 theme pregnant 1443:1450 arg1 samples 1468:1474 pregnant vs. nonpregnant samples 1443:1474 pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1443:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 4 9 theme pregnancy-associated 1165:1184 arg1 decrease 1186:1193 a pregnancy-associated decrease 1163:1193 a pregnancy-associated decrease in the total content of oligomannose chains 1163:1237 Surprisingly, there was a pregnancy-associated decrease in the total content of oligomannose chains due predominantly to a reduction in Man5GlcNAc2-R and Man6GlcNAc2-R. 2136357 2 10 theme inhibitory 786:795 arg1 Biol 843:846 Biol 843:846 Biol 843:846 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 2 10 theme inhibitory 786:795 arg1 Man9GlcNAc2-R 763:775 Man9GlcNAc2-R 763:775 Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al. 763:828 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 1 11 dep Science 407:413 arg1 1987 458:461 1987 458:461 1987 458:461 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 11 dep Science 407:413 arg1 Decker 450:455 Decker 450:455 Decker 450:455 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 11 dep Science 407:413 arg1 Shifrin 438:444 Shifrin 438:444 Shifrin 438:444 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 3 12 theme bovine 1123:1128 arg1 sources 1130:1136 both human and bovine sources 1108:1136 both human and bovine sources 1108:1136 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 4 13 from reduction 1262:1270 arg1 Man6GlcNAc2-R 1293:1305 Man6GlcNAc2-R 1293:1305 Man6GlcNAc2-R 1293:1305 Surprisingly, there was a pregnancy-associated decrease in the total content of oligomannose chains due predominantly to a reduction in Man5GlcNAc2-R and Man6GlcNAc2-R. 2136357 4 13 from reduction 1262:1270 arg1 Man5GlcNAc2-R 1275:1287 Man5GlcNAc2-R 1275:1287 Man5GlcNAc2-R 1275:1287 Surprisingly, there was a pregnancy-associated decrease in the total content of oligomannose chains due predominantly to a reduction in Man5GlcNAc2-R and Man6GlcNAc2-R. 2136357 3 14 theme inhibitory 932:941 arg1 activity 943:950 pregnancy-associated inhibitory activity 911:950 pregnancy-associated inhibitory activity 911:950 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 3 15 dep uromodulin 1073:1082 arg1 pregnant 1085:1092 pregnant 1085:1092 pregnant 1085:1092 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 1 16 dep 1985 358:361 arg1 Science 364:370 Science 364:370 Science 364:370 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 16 dep 1985 358:361 arg1 Science 407:413 Science 407:413 Science 407:413 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 3 17 theme Tamm-Horsfall 1019:1031 arg1 glycoprotein 1033:1044 Tamm-Horsfall glycoprotein 1019:1044 Tamm-Horsfall glycoprotein (nonpregnant) 1019:1058 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 3 18 theme activity 943:950 arg1 observation 896:906 the observation 892:906 the observation of pregnancy-associated inhibitory activity to a second species 892:970 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 5 19 from chains 1433:1438 arg1 samples 1468:1474 pregnant vs. nonpregnant samples 1443:1474 pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1443:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 5 19 from chains 1433:1438 arg1 species 1486:1492 both species 1481:1492 both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1481:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 2 20 attach derived 543:549 arg2 glycopeptides 529:541 the Man6(7)GlcNAc2-R glycopeptides 508:541 the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin 508:565 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 2 20 attach derived 543:549 arg1 uromodulin 556:565 uromodulin 556:565 uromodulin 556:565 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 3 21 theme human 1113:1117 arg1 sources 1130:1136 both human and bovine sources 1108:1136 both human and bovine sources 1108:1136 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 2 22 gly glycopeptides 704:716 arg2 glycopeptides 704:716 oligomannose glycopeptides 691:716 oligomannose glycopeptides from other sources 691:735 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 2 22 gly glycopeptides 704:716 arg1 sources 729:735 other sources 723:735 other sources 723:735 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 3 23 theme glycoprotein 1033:1044 arg1 profile 1008:1014 the oligomannose profile 991:1014 the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) 991:1058 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 2 24 theme further 641:647 arg1 studies 649:655 further studies 641:655 further studies 641:655 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 1 25 theme pregnancy-associated 199:218 arg1 ability 220:226 a pregnancy-associated ability 197:226 a pregnancy-associated ability to inhibit antigen-specific T cell proliferation 197:275 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 3 26 gly glycoprotein 1033:1044 arg1 glycoprotein 1033:1044 Tamm-Horsfall glycoprotein 1019:1044 Tamm-Horsfall glycoprotein (nonpregnant) 1019:1058 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 2 27 theme cell 594:597 arg1 proliferation 599:611 antigen-specific T cell proliferation 575:611 antigen-specific T cell proliferation 575:611 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 5 28 dep human 1495:1499 arg1 % 1540:1540 7.2% 1537:1540 7.2% 1537:1540 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 5 28 dep human 1495:1499 arg1 bovine 1519:1524 bovine 1519:1524 bovine 1519:1524 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 5 28 dep human 1495:1499 arg1 % 1506:1506 34.6% 1502:1506 34.6% 1502:1506 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 5 28 dep human 1495:1499 arg1 % 1516:1516 25.9% 1512:1516 25.9% 1512:1516 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 5 28 dep human 1495:1499 arg1 % 1531:1531 14.4% 1527:1531 14.4% 1527:1531 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 0 29 gly glycoprotein 108:119 arg1 uromodulin 82:91 human and bovine uromodulin 65:91 human and bovine uromodulin (Tamm-Horsfall glycoprotein) 65:120 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 0 29 gly glycoprotein 108:119 arg1 glycoprotein 108:119 Tamm-Horsfall glycoprotein 94:119 Tamm-Horsfall glycoprotein 94:119 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 3 30 attach derived 1095:1101 arg1 sources 1130:1136 both human and bovine sources 1108:1136 both human and bovine sources 1108:1136 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 3 30 attach derived 1095:1101 arg2 uromodulin 1073:1082 uromodulin 1073:1082 uromodulin (pregnant) derived from both human and bovine sources 1073:1136 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 0 31 theme Pregnancy-associated 0:19 arg1 changes 21:27 Pregnancy-associated changes 0:27 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 0:121 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 2 32 theme T 592:592 arg1 proliferation 599:611 antigen-specific T cell proliferation 575:611 antigen-specific T cell proliferation 575:611 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 3 33 theme second 957:962 arg1 species 964:970 a second species 955:970 a second species 955:970 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 5 34 theme greater 1388:1394 arg1 proportion 1396:1405 a significantly greater proportion 1372:1405 a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1372:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 0 35 theme oligomannose 32:43 arg1 oligosaccharides 45:60 oligomannose oligosaccharides 32:60 oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein) 32:120 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 1 36 theme carbohydrate 316:327 arg1 moiety 329:334 a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53] 314:485 moiety 329:334 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 37 gly glycoprotein 135:146 arg1 glycoprotein 135:146 The urinary glycoprotein uromodulin 123:157 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) 123:186 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 3 38 theme pregnancy-associated 911:930 arg1 activity 943:950 pregnancy-associated inhibitory activity 911:950 pregnancy-associated inhibitory activity 911:950 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 1 39 theme antigen-specific 239:254 arg1 proliferation 263:275 antigen-specific T cell proliferation 239:275 antigen-specific T cell proliferation 239:275 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 40 dep Science 364:370 arg1 Hession 384:390 Hession 384:390 Hession 384:390 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 2 41 theme Man6 512:515 arg1 glycopeptides 529:541 the Man6(7)GlcNAc2-R glycopeptides 508:541 the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin 508:565 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 1 42 dep ability 220:226 arg1 inhibit 231:237 inhibit 231:237 to inhibit antigen-specific T cell proliferation 228:275 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 43 theme T 256:256 arg1 proliferation 263:275 antigen-specific T cell proliferation 239:275 antigen-specific T cell proliferation 239:275 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 4 44 theme chains 1232:1237 arg1 content 1208:1214 the total content 1198:1214 the total content of oligomannose chains 1198:1237 Surprisingly, there was a pregnancy-associated decrease in the total content of oligomannose chains due predominantly to a reduction in Man5GlcNAc2-R and Man6GlcNAc2-R. 2136357 2 45 with inhibitory 746:755 arg1 Biol 843:846 Biol 843:846 Biol 843:846 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 2 45 with inhibitory 746:755 arg1 Man9GlcNAc2-R 763:775 Man9GlcNAc2-R 763:775 Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al. 763:828 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 1 46 theme cell 258:261 arg1 proliferation 263:275 antigen-specific T cell proliferation 239:275 antigen-specific T cell proliferation 239:275 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 47 gly glycoprotein 174:185 arg1 uromodulin 148:157 The urinary glycoprotein uromodulin 123:157 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) 123:186 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 47 gly glycoprotein 174:185 arg1 glycoprotein 174:185 Tamm-Horsfall glycoprotein 160:185 Tamm-Horsfall glycoprotein 160:185 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 4 48 theme oligomannose 1219:1230 arg1 chains 1232:1237 oligomannose chains 1219:1237 oligomannose chains 1219:1237 Surprisingly, there was a pregnancy-associated decrease in the total content of oligomannose chains due predominantly to a reduction in Man5GlcNAc2-R and Man6GlcNAc2-R. 2136357 2 49 from sources 729:735 arg1 glycopeptides 704:716 oligomannose glycopeptides 691:716 oligomannose glycopeptides from other sources 691:735 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 1 50 theme urinary 127:133 arg1 uromodulin 148:157 The urinary glycoprotein uromodulin 123:157 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) 123:186 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 50 theme urinary 127:133 arg1 glycoprotein 174:185 Tamm-Horsfall glycoprotein 160:185 Tamm-Horsfall glycoprotein 160:185 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 0 51 theme human 65:69 arg1 uromodulin 82:91 human and bovine uromodulin 65:91 human and bovine uromodulin (Tamm-Horsfall glycoprotein) 65:120 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 0 51 theme human 65:69 arg1 glycoprotein 108:119 Tamm-Horsfall glycoprotein 94:119 Tamm-Horsfall glycoprotein 94:119 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 1 52 dep Hession 384:390 arg1 al 395:396 Hession et al 384:396 Science 229:479-81; Hession et al. 364:397 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 3 53 dep glycoprotein 1033:1044 arg1 nonpregnant 1047:1057 nonpregnant 1047:1057 nonpregnant 1047:1057 In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. 2136357 1 54 theme glycoprotein 135:146 arg1 uromodulin 148:157 The urinary glycoprotein uromodulin 123:157 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) 123:186 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 54 theme glycoprotein 135:146 arg1 glycoprotein 174:185 Tamm-Horsfall glycoprotein 160:185 Tamm-Horsfall glycoprotein 160:185 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 5 55 theme total 1414:1418 arg1 chains 1433:1438 the total oligomannose chains 1410:1438 the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1410:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 2 56 theme GlcNAc2-R 519:527 arg1 glycopeptides 529:541 the Man6(7)GlcNAc2-R glycopeptides 508:541 the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin 508:565 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 2 57 theme other 723:727 arg1 sources 729:735 other sources 723:735 other sources 723:735 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 5 58 theme oligomannose 1420:1431 arg1 chains 1433:1438 the total oligomannose chains 1410:1438 the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1410:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 5 59 from species 1486:1492 arg1 samples 1468:1474 pregnant vs. nonpregnant samples 1443:1474 pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1443:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 5 59 from species 1486:1492 arg1 chains 1433:1438 the total oligomannose chains 1410:1438 the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1410:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 4 60 from decrease 1186:1193 arg1 content 1208:1214 the total content 1198:1214 the total content of oligomannose chains 1198:1237 Surprisingly, there was a pregnancy-associated decrease in the total content of oligomannose chains due predominantly to a reduction in Man5GlcNAc2-R and Man6GlcNAc2-R. 2136357 4 61 theme total 1202:1206 arg1 content 1208:1214 the total content 1198:1214 the total content of oligomannose chains 1198:1237 Surprisingly, there was a pregnancy-associated decrease in the total content of oligomannose chains due predominantly to a reduction in Man5GlcNAc2-R and Man6GlcNAc2-R. 2136357 2 62 theme oligomannose 691:702 arg1 glycopeptides 704:716 oligomannose glycopeptides 691:716 oligomannose glycopeptides from other sources 691:735 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 5 63 from proportion 1396:1405 arg1 samples 1468:1474 pregnant vs. nonpregnant samples 1443:1474 pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1443:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 0 64 theme uromodulin 82:91 arg1 oligosaccharides 45:60 oligomannose oligosaccharides 32:60 oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein) 32:120 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 2 65 theme tested 806:811 arg1 [Muchmore 813:821 those tested [Muchmore 800:821 those tested [Muchmore 800:821 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 1 66 theme Tamm-Horsfall 160:172 arg1 uromodulin 148:157 The urinary glycoprotein uromodulin 123:157 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) 123:186 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 66 theme Tamm-Horsfall 160:172 arg1 glycoprotein 174:185 Tamm-Horsfall glycoprotein 160:185 Tamm-Horsfall glycoprotein 160:185 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 1 67 dep Shifrin 438:444 arg1 Immunol 466:472 Immunol 466:472 Immunol 466:472 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 0 68 theme bovine 75:80 arg1 uromodulin 82:91 human and bovine uromodulin 65:91 human and bovine uromodulin (Tamm-Horsfall glycoprotein) 65:120 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 0 68 theme bovine 75:80 arg1 glycoprotein 108:119 Tamm-Horsfall glycoprotein 94:119 Tamm-Horsfall glycoprotein 94:119 Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein). 2136357 1 69 dep moiety 329:334 arg1 [Muchmore 336:344 [Muchmore 336:344 [Muchmore 336:344 The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. 2136357 5 70 from samples 1468:1474 arg1 proportion 1396:1405 a significantly greater proportion 1372:1405 a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%) 1372:1541 Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%). 2136357 2 71 from microM 629:634 arg1 % 618:618 50% 616:618 50% at 0.2-2 microM 616:634 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 2 72 gly glycopeptides 529:541 arg2 glycopeptides 529:541 the Man6(7)GlcNAc2-R glycopeptides 508:541 the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin 508:565 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 2136357 2 73 theme [Muchmore 813:821 arg1 inhibitory 786:795 inhibitory 786:795 inhibitory 786:795 We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. 8384526 0 0 theme oligosaccharides 63:78 arg1 structure 44:52 the structure 40:52 the structure of small oligosaccharides of glycoproteins 40:95 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 3 1 theme intact 754:759 arg1 fractions 761:769 the intact fractions 750:769 the intact fractions 750:769 The anomeric configuration was determined by 1H NMR spectroscopy of the intact fractions. 8384526 0 2 theme gel 329:331 arg1 filtration 333:342 gel filtration 329:342 gel filtration 329:342 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 2 3 theme monosaccharide 586:599 arg1 sequence 601:608 the monosaccharide sequence and linkage positions 582:630 sequence 601:608 The resulting data allowed the monosaccharide sequence and linkage positions to be assigned to each component of the mixtures. 8384526 0 4 theme small 57:61 arg1 oligosaccharides 63:78 small oligosaccharides 57:78 small oligosaccharides of glycoproteins 57:95 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 2 5 theme linkage 614:620 arg1 positions 622:630 the monosaccharide sequence and linkage positions 582:630 positions 622:630 The resulting data allowed the monosaccharide sequence and linkage positions to be assigned to each component of the mixtures. 8384526 4 6 theme other 866:870 arg1 products 878:885 five other minor products 861:885 five other minor products 861:885 The structures of a desialylated tetrasaccharide, two monosialylated trisaccharides, and five other minor products were defined. 8384526 0 7 theme glycoproteins 83:95 arg1 oligosaccharides 63:78 small oligosaccharides 57:78 small oligosaccharides of glycoproteins 57:95 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 8 theme human 191:195 arg1 A 209:209 purified human glycophorin A 182:209 purified human glycophorin A 182:209 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 9 dep cleaved 237:243 arg1 approach 12:19 An improved approach 0:19 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins 0:95 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 10 theme purified 182:189 arg1 A 209:209 purified human glycophorin A 182:209 purified human glycophorin A 182:209 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 11 theme oligosaccharide 249:263 arg1 chains 270:275 the oligosaccharide side chains 245:275 the oligosaccharide side chains 245:275 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 12 theme A 209:209 arg1 Treatment 169:177 human glycophorin A. Treatment 148:177 human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride 148:235 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 13 link O-linked 117:124 arg1 oligosaccharides 126:141 the O-linked oligosaccharides 113:141 the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride 113:235 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 3 14 theme 1H 727:728 arg1 spectroscopy 734:745 1H NMR spectroscopy 727:745 1H NMR spectroscopy of the intact fractions 727:769 The anomeric configuration was determined by 1H NMR spectroscopy of the intact fractions. 8384526 0 15 theme glycophorin 197:207 arg1 A 209:209 purified human glycophorin A 182:209 purified human glycophorin A 182:209 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 16 theme improved 3:10 arg1 approach 12:19 An improved approach 0:19 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins 0:95 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 3 17 theme NMR 730:732 arg1 spectroscopy 734:745 1H NMR spectroscopy 727:745 1H NMR spectroscopy of the intact fractions 727:769 The anomeric configuration was determined by 1H NMR spectroscopy of the intact fractions. 8384526 0 18 theme alkaline 216:223 arg1 borohydride 225:235 alkaline borohydride 216:235 alkaline borohydride 216:235 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 19 theme side 265:268 arg1 chains 270:275 the oligosaccharide side chains 245:275 the oligosaccharide side chains 245:275 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 20 with Treatment 169:177 arg1 borohydride 225:235 alkaline borohydride 216:235 alkaline borohydride 216:235 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 3 21 theme fractions 761:769 arg1 spectroscopy 734:745 1H NMR spectroscopy 727:745 1H NMR spectroscopy of the intact fractions 727:769 The anomeric configuration was determined by 1H NMR spectroscopy of the intact fractions. 8384526 4 22 theme minor 872:876 arg1 products 878:885 five other minor products 861:885 five other minor products 861:885 The structures of a desialylated tetrasaccharide, two monosialylated trisaccharides, and five other minor products were defined. 8384526 0 23 gly glycoproteins 83:95 arg1 glycoproteins 83:95 glycoproteins 83:95 glycoproteins 83:95 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 24 theme molecular 371:379 arg1 compounds 388:396 low molecular weight compounds 367:396 low molecular weight compounds 367:396 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 2 25 theme resulting 559:567 arg1 data 569:572 The resulting data 555:572 The resulting data 555:572 The resulting data allowed the monosaccharide sequence and linkage positions to be assigned to each component of the mixtures. 8384526 2 26 theme mixtures 672:679 arg1 component 655:663 each component 650:663 each component of the mixtures 650:679 The resulting data allowed the monosaccharide sequence and linkage positions to be assigned to each component of the mixtures. 8384526 0 27 theme low 367:369 arg1 compounds 388:396 low molecular weight compounds 367:396 low molecular weight compounds 367:396 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 28 theme compounds 388:396 arg1 mixtures 355:362 three mixtures 349:362 three mixtures of low molecular weight compounds 349:396 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 4 29 gly desialylated 792:803 arg1 tetrasaccharide 805:819 a desialylated tetrasaccharide 790:819 a desialylated tetrasaccharide 790:819 The structures of a desialylated tetrasaccharide, two monosialylated trisaccharides, and five other minor products were defined. 8384526 0 30 from Treatment 169:177 arg1 oligosaccharides 126:141 the O-linked oligosaccharides 113:141 the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride 113:235 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 31 theme weight 381:386 arg1 compounds 388:396 low molecular weight compounds 367:396 low molecular weight compounds 367:396 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 32 theme O-linked 117:124 arg1 oligosaccharides 126:141 the O-linked oligosaccharides 113:141 the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride 113:235 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 4 33 theme monosialylated 826:839 arg1 trisaccharides 841:854 two monosialylated trisaccharides 822:854 two monosialylated trisaccharides 822:854 The structures of a desialylated tetrasaccharide, two monosialylated trisaccharides, and five other minor products were defined. 8384526 0 34 theme human 148:152 arg1 glycophorin 154:164 human glycophorin 148:164 human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride 148:235 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 35 theme alditol 286:292 arg1 derivatives 294:304 alditol derivatives 286:304 alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds 286:396 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 0 36 theme A. 166:167 arg1 Treatment 169:177 human glycophorin A. Treatment 148:177 human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride 148:235 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 3 37 theme anomeric 686:693 arg1 configuration 695:707 The anomeric configuration 682:707 The anomeric configuration 682:707 The anomeric configuration was determined by 1H NMR spectroscopy of the intact fractions. 8384526 4 38 theme tetrasaccharide 805:819 arg1 structures 776:785 The structures 772:785 The structures of a desialylated tetrasaccharide 772:819 The structures of a desialylated tetrasaccharide, two monosialylated trisaccharides, and five other minor products were defined. 8384526 4 38 theme tetrasaccharide 805:819 arg1 products 878:885 five other minor products 861:885 five other minor products 861:885 The structures of a desialylated tetrasaccharide, two monosialylated trisaccharides, and five other minor products were defined. 8384526 4 38 theme tetrasaccharide 805:819 arg1 trisaccharides 841:854 two monosialylated trisaccharides 822:854 two monosialylated trisaccharides 822:854 The structures of a desialylated tetrasaccharide, two monosialylated trisaccharides, and five other minor products were defined. 8384526 0 39 theme glycophorin 154:164 arg1 Treatment 169:177 human glycophorin A. Treatment 148:177 human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride 148:235 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 4 40 theme desialylated 792:803 arg1 tetrasaccharide 805:819 a desialylated tetrasaccharide 790:819 a desialylated tetrasaccharide 790:819 The structures of a desialylated tetrasaccharide, two monosialylated trisaccharides, and five other minor products were defined. 8384526 0 41 theme structure 44:52 arg1 analysis 28:35 the analysis 24:35 the analysis of the structure of small oligosaccharides of glycoproteins 24:95 An improved approach to the analysis of the structure of small oligosaccharides of glycoproteins: application to the O-linked oligosaccharides from human glycophorin A. Treatment of purified human glycophorin A with alkaline borohydride cleaved the oligosaccharide side chains to yield alditol derivatives that were separated by gel filtration into three mixtures of low molecular weight compounds. 8384526 4 42 gly monosialylated 826:839 arg1 trisaccharides 841:854 two monosialylated trisaccharides 822:854 two monosialylated trisaccharides 822:854 The structures of a desialylated tetrasaccharide, two monosialylated trisaccharides, and five other minor products were defined. 681341 2 0 theme O 442:442 arg1 individuals 444:454 blood type O individuals 431:454 blood type O individuals 431:454 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 4 1 theme blood 856:860 arg1 erythrocyte 869:879 blood type O erythrocyte 856:879 blood type O erythrocyte 856:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 2 2 dep 3 603:603 arg1 leads 617:621 leads 617:621 leads to 6 617:626 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 2 3 theme type 437:440 arg1 individuals 444:454 blood type O individuals 431:454 blood type O individuals 431:454 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 4 4 theme sugar 1037:1041 arg1 patterns 1062:1069 the same radioactive sugar chain distribution patterns 1016:1069 the same radioactive sugar chain distribution patterns 1016:1069 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 0 5 theme erythrocyte 87:97 arg1 membrane 99:106 human erythrocyte membrane 81:106 human erythrocyte membrane 81:106 The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. 681341 4 6 theme glycoproteins 828:840 arg1 acceptors 896:904 acceptors 896:904 acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals 896:1003 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 6 theme glycoproteins 828:840 arg1 chains 809:814 Both large and small neutral sugar chains 774:814 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte 774:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 7 theme radioactive 1025:1035 arg1 patterns 1062:1069 the same radioactive sugar chain distribution patterns 1016:1069 the same radioactive sugar chain distribution patterns 1016:1069 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 5 8 theme enzymes 1167:1173 arg1 chain 1098:1102 the acidic sugar chain 1081:1102 the acidic sugar chain with the H determinant 1081:1125 However, the acidic sugar chain with the H determinant could not serve as an acceptor of these enzymes. 681341 5 8 theme enzymes 1167:1173 arg1 acceptor 1149:1156 an acceptor 1146:1156 an acceptor of these enzymes 1146:1173 However, the acidic sugar chain with the H determinant could not serve as an acceptor of these enzymes. 681341 0 9 theme human 81:85 arg1 membrane 99:106 human erythrocyte membrane 81:106 human erythrocyte membrane 81:106 The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. 681341 4 10 theme membrane 819:826 arg1 glycoproteins 828:840 membrane glycoproteins 819:840 membrane glycoproteins obtained from blood type O erythrocyte 819:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 0 11 gly glycoproteins 53:65 arg1 glycoproteins 53:65 ABO blood group active glycoproteins 30:65 ABO blood group active glycoproteins 30:65 The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. 681341 4 12 theme alpha-N-acetylgalactosaminyltransferases 909:948 arg1 acceptors 896:904 acceptors 896:904 acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals 896:1003 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 12 theme alpha-N-acetylgalactosaminyltransferases 909:948 arg1 chains 809:814 Both large and small neutral sugar chains 774:814 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte 774:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 1 13 contain have 157:160 arg2 groups 166:171 two groups 162:171 two groups of sugar chains 162:187 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 1 13 contain have 157:160 arg2 chains 182:187 sugar chains 176:187 sugar chains 176:187 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 1 13 contain have 157:160 arg1 glycoproteins 113:125 The glycoproteins 109:125 The glycoproteins of human erythrocyte membrane 109:155 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 4 14 theme small 789:793 arg1 acceptors 896:904 acceptors 896:904 acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals 896:1003 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 14 theme small 789:793 arg1 chains 809:814 Both large and small neutral sugar chains 774:814 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte 774:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 2 15 theme 3 603:603 arg1 N-acetylgalactosaminitol 628:651 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol 603:651 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol 603:651 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 2 16 theme small 343:347 arg1 group 354:358 the small size group 339:358 the small size group 339:358 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 2 17 dep Fucalpha1 565:573 arg1 leads 575:579 leads 575:579 leads to 2Galbeta1 575:592 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 3 18 theme molecular 672:680 arg1 more 758:761 more 758:761 more 758:761 The molecular weight of the large sugar chains with ABH determinants were estimated to be more than 4000. 681341 3 18 theme molecular 672:680 arg1 weight 682:687 The molecular weight 668:687 The molecular weight of the large sugar chains with ABH determinants 668:735 The molecular weight of the large sugar chains with ABH determinants were estimated to be more than 4000. 681341 2 19 theme blood 431:435 arg1 individuals 444:454 blood type O individuals 431:454 blood type O individuals 431:454 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 2 20 theme size 349:352 arg1 group 354:358 the small size group 339:358 the small size group 339:358 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 0 21 theme sugar 4:8 arg1 structures 16:25 The sugar chain structures 0:25 The sugar chain structures of ABO blood group active glycoproteins 0:65 The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. 681341 5 22 theme acidic 1085:1090 arg1 chain 1098:1102 the acidic sugar chain 1081:1102 the acidic sugar chain with the H determinant 1081:1125 However, the acidic sugar chain with the H determinant could not serve as an acceptor of these enzymes. 681341 5 22 theme acidic 1085:1090 arg1 acceptor 1149:1156 an acceptor 1146:1156 an acceptor of these enzymes 1146:1173 However, the acidic sugar chain with the H determinant could not serve as an acceptor of these enzymes. 681341 4 23 theme sugar 803:807 arg1 acceptors 896:904 acceptors 896:904 acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals 896:1003 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 23 theme sugar 803:807 arg1 chains 809:814 Both large and small neutral sugar chains 774:814 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte 774:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 3 24 theme chains 708:713 arg1 more 758:761 more 758:761 more 758:761 The molecular weight of the large sugar chains with ABH determinants were estimated to be more than 4000. 681341 3 24 theme chains 708:713 arg1 weight 682:687 The molecular weight 668:687 The molecular weight of the large sugar chains with ABH determinants 668:735 The molecular weight of the large sugar chains with ABH determinants were estimated to be more than 4000. 681341 1 25 theme sugar 176:180 arg1 chains 182:187 sugar chains 176:187 sugar chains 176:187 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 4 26 theme A2 990:991 arg1 individuals 993:1003 blood type A1 and A2 individuals 972:1003 blood type A1 and A2 individuals 972:1003 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 1 27 theme molecular 257:265 arg1 sizes 267:271 their molecular sizes 251:271 their molecular sizes 251:271 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 1 28 from sizes 267:271 arg1 distinct 239:246 distinct 239:246 distinct 239:246 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 3 29 with chains 708:713 arg1 determinants 724:735 ABH determinants 720:735 ABH determinants 720:735 The molecular weight of the large sugar chains with ABH determinants were estimated to be more than 4000. 681341 1 30 theme chains 182:187 arg1 groups 166:171 two groups 162:171 two groups of sugar chains 162:187 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 1 30 theme chains 182:187 arg1 chains 182:187 sugar chains 176:187 sugar chains 176:187 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 1 31 gly glycoproteins 113:125 arg1 glycoproteins 113:125 The glycoproteins 109:125 The glycoproteins of human erythrocyte membrane 109:155 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 2 32 theme sugar 284:288 arg1 chain 290:294 A neutral sugar chain 274:294 A neutral sugar chain 274:294 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 0 33 theme chain 10:14 arg1 structures 16:25 The sugar chain structures 0:25 The sugar chain structures of ABO blood group active glycoproteins 0:65 The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. 681341 3 34 theme large 696:700 arg1 chains 708:713 the large sugar chains 692:713 the large sugar chains with ABH determinants 692:735 The molecular weight of the large sugar chains with ABH determinants were estimated to be more than 4000. 681341 4 35 theme O 867:867 arg1 erythrocyte 869:879 blood type O erythrocyte 856:879 blood type O erythrocyte 856:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 2 36 attach isolated 366:373 arg2 chain 290:294 A neutral sugar chain 274:294 A neutral sugar chain 274:294 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 2 36 attach isolated 366:373 arg2 chain 316:320 an acidic sugar chain 300:320 an acidic sugar chain 300:320 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 2 36 attach isolated 366:373 arg1 glycoproteins 384:396 the glycoproteins 380:396 the glycoproteins obtained from the erythrocyte of blood type O individuals 380:454 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 2 37 theme neutral 276:282 arg1 chain 290:294 A neutral sugar chain 274:294 A neutral sugar chain 274:294 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 1 38 theme blood 194:198 arg1 determinants 209:220 blood type ABH determinants 194:220 blood type ABH determinants 194:220 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 0 39 theme ABO 30:32 arg1 glycoproteins 53:65 ABO blood group active glycoproteins 30:65 ABO blood group active glycoproteins 30:65 The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. 681341 3 40 theme sugar 702:706 arg1 chains 708:713 the large sugar chains 692:713 the large sugar chains with ABH determinants 692:735 The molecular weight of the large sugar chains with ABH determinants were estimated to be more than 4000. 681341 4 41 gly glycoproteins 828:840 arg1 glycoproteins 828:840 membrane glycoproteins 819:840 membrane glycoproteins obtained from blood type O erythrocyte 819:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 1 42 theme type 200:203 arg1 determinants 209:220 blood type ABH determinants 194:220 blood type ABH determinants 194:220 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 4 43 theme blood 972:976 arg1 A1 983:984 blood type A1 972:984 blood type A1 972:984 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 44 theme A1 983:984 arg1 individuals 993:1003 blood type A1 and A2 individuals 972:1003 blood type A1 and A2 individuals 972:1003 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 1 45 from distinct 239:246 arg1 sizes 267:271 their molecular sizes 251:271 their molecular sizes 251:271 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 1 46 theme ABH 205:207 arg1 determinants 209:220 blood type ABH determinants 194:220 blood type ABH determinants 194:220 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 0 47 theme group 40:44 arg1 glycoproteins 53:65 ABO blood group active glycoproteins 30:65 ABO blood group active glycoproteins 30:65 The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. 681341 5 48 theme H 1113:1113 arg1 determinant 1115:1125 the H determinant 1109:1125 the H determinant 1109:1125 However, the acidic sugar chain with the H determinant could not serve as an acceptor of these enzymes. 681341 2 49 theme individuals 444:454 arg1 erythrocyte 416:426 the erythrocyte 412:426 the erythrocyte of blood type O individuals 412:454 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 4 50 theme large 779:783 arg1 acceptors 896:904 acceptors 896:904 acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals 896:1003 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 50 theme large 779:783 arg1 chains 809:814 Both large and small neutral sugar chains 774:814 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte 774:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 51 theme neutral 795:801 arg1 acceptors 896:904 acceptors 896:904 acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals 896:1003 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 51 theme neutral 795:801 arg1 chains 809:814 Both large and small neutral sugar chains 774:814 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte 774:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 0 52 theme blood 34:38 arg1 glycoproteins 53:65 ABO blood group active glycoproteins 30:65 ABO blood group active glycoproteins 30:65 The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. 681341 3 53 theme ABH 720:722 arg1 determinants 724:735 ABH determinants 720:735 ABH determinants 720:735 The molecular weight of the large sugar chains with ABH determinants were estimated to be more than 4000. 681341 2 54 theme sugar 310:314 arg1 chain 316:320 an acidic sugar chain 300:320 an acidic sugar chain 300:320 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 4 55 theme distribution 1049:1060 arg1 patterns 1062:1069 the same radioactive sugar chain distribution patterns 1016:1069 the same radioactive sugar chain distribution patterns 1016:1069 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 56 theme type 862:865 arg1 erythrocyte 869:879 blood type O erythrocyte 856:879 blood type O erythrocyte 856:879 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 2 57 theme acidic 303:308 arg1 chain 316:320 an acidic sugar chain 300:320 an acidic sugar chain 300:320 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 4 58 theme chain 1043:1047 arg1 patterns 1062:1069 the same radioactive sugar chain distribution patterns 1016:1069 the same radioactive sugar chain distribution patterns 1016:1069 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 4 59 theme type 978:981 arg1 A1 983:984 blood type A1 972:984 blood type A1 972:984 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 1 60 theme human 130:134 arg1 membrane 148:155 human erythrocyte membrane 130:155 human erythrocyte membrane 130:155 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 0 61 theme glycoproteins 53:65 arg1 structures 16:25 The sugar chain structures 0:25 The sugar chain structures of ABO blood group active glycoproteins 0:65 The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. 681341 5 62 with chain 1098:1102 arg1 determinant 1115:1125 the H determinant 1109:1125 the H determinant 1109:1125 However, the acidic sugar chain with the H determinant could not serve as an acceptor of these enzymes. 681341 1 63 theme erythrocyte 136:146 arg1 membrane 148:155 human erythrocyte membrane 130:155 human erythrocyte membrane 130:155 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 4 64 theme individuals 993:1003 arg1 milk 964:967 milk 964:967 milk of blood type A1 and A2 individuals 964:1003 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 681341 0 65 theme active 46:51 arg1 glycoproteins 53:65 ABO blood group active glycoproteins 30:65 ABO blood group active glycoproteins 30:65 The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. 681341 5 66 theme sugar 1092:1096 arg1 chain 1098:1102 the acidic sugar chain 1081:1102 the acidic sugar chain with the H determinant 1081:1125 However, the acidic sugar chain with the H determinant could not serve as an acceptor of these enzymes. 681341 5 66 theme sugar 1092:1096 arg1 acceptor 1149:1156 an acceptor 1146:1156 an acceptor of these enzymes 1146:1173 However, the acidic sugar chain with the H determinant could not serve as an acceptor of these enzymes. 681341 2 67 gly glycoproteins 384:396 arg1 glycoproteins 384:396 the glycoproteins 380:396 the glycoproteins obtained from the erythrocyte of blood type O individuals 380:454 A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. 681341 1 68 theme membrane 148:155 arg1 glycoproteins 113:125 The glycoproteins 109:125 The glycoproteins of human erythrocyte membrane 109:155 The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. 681341 4 69 theme same 1020:1023 arg1 patterns 1062:1069 the same radioactive sugar chain distribution patterns 1016:1069 the same radioactive sugar chain distribution patterns 1016:1069 Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. 2731547 6 0 theme rich 1053:1056 arg1 mucins 1040:1045 These mucins 1034:1045 These mucins 1034:1045 These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. 2731547 6 0 theme rich 1053:1056 arg1 source 1058:1063 a rich source 1051:1063 a rich source of carbohydrate structures which express multiple blood group activities 1051:1136 These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. 2731547 14 1 theme 1H-NMR 2481:2486 arg1 spectroscopy 2488:2499 1H-NMR spectroscopy 2481:2499 1H-NMR spectroscopy 2481:2499 Using methylation analysis, 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry (FAB-MS), we propose the primary structure for 19 major oligosaccharides. 2731547 11 2 theme anion-exchange 2086:2099 arg1 column 2101:2106 an anion-exchange column 2083:2106 an anion-exchange column 2083:2106 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 1 3 gly glycoproteins 215:227 arg1 glycoproteins 215:227 human meconium glycoproteins 200:227 human meconium glycoproteins 200:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 9 4 theme further 1587:1593 arg1 studies 1595:1601 further studies 1587:1601 further studies 1587:1601 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 8 5 theme same 1387:1390 arg1 group 1392:1396 the same group 1383:1396 the same group 1383:1396 In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. 2731547 1 6 theme meconium 206:213 arg1 glycoproteins 215:227 human meconium glycoproteins 200:227 human meconium glycoproteins 200:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 13 7 theme different 2349:2357 arg1 size 2359:2362 different size 2349:2362 different size 2349:2362 Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. 2731547 5 8 theme mucin 1022:1026 arg1 type 1028:1031 the mucin type 1018:1031 the mucin type 1018:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 6 9 theme blood 1115:1119 arg1 activities 1127:1136 multiple blood group activities 1106:1136 multiple blood group activities 1106:1136 These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. 2731547 5 10 dep glycoproteins 898:910 arg1 see 873:875 see 873:875 see text 873:880 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 4 11 theme 400-MHz 774:780 arg1 spectroscopy 789:800 400-MHz 1H-NMR spectroscopy 774:800 400-MHz 1H-NMR spectroscopy 774:800 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 11 12 theme borohydride 1996:2006 arg1 degradation 2008:2018 alkaline borohydride degradation 1987:2018 alkaline borohydride degradation of human meconium glycoproteins 1987:2050 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 7 13 theme previous 1225:1232 arg1 study 1234:1238 A previous study [5] 1223:1242 A previous study [5] 1223:1242 A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. 2731547 12 14 theme reversed-phase 2171:2184 arg1 chromatography 2186:2199 normal-phase and reversed-phase chromatography 2154:2199 chromatography 2186:2199 The neutral fraction was further purified by normal-phase and reversed-phase chromatography while acidic fractions were fractionated only by normal-phase chromatography. 2731547 9 15 theme monosaccharides 1648:1662 arg1 structures 1623:1632 the structures 1619:1632 the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors 1619:1794 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 4 16 theme primary 514:520 arg1 analysis 533:540 the primary structural analysis 510:540 the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy 510:800 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 5 17 theme molecular 956:964 arg1 compounds 971:979 high molecular mass compounds 951:979 high molecular mass compounds with numerous carbohydrate chains of the mucin type 951:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 5 17 theme molecular 956:964 arg1 glycoproteins 898:910 The intestinal glycoproteins 883:910 (formula; see text) The intestinal glycoproteins of human meconium 863:928 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 5 18 theme carbohydrate 995:1006 arg1 chains 1008:1013 numerous carbohydrate chains 986:1013 numerous carbohydrate chains of the mucin type 986:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 6 19 theme structures 1081:1090 arg1 mucins 1040:1045 These mucins 1034:1045 These mucins 1034:1045 These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. 2731547 6 19 theme structures 1081:1090 arg1 source 1058:1063 a rich source 1051:1063 a rich source of carbohydrate structures which express multiple blood group activities 1051:1136 These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. 2731547 11 20 theme meconium 2029:2036 arg1 glycoproteins 2038:2050 human meconium glycoproteins 2023:2050 human meconium glycoproteins 2023:2050 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 10 21 gly glycopeptides 1847:1859 arg2 glycopeptides 1847:1859 meconium glycopeptides 1838:1859 meconium glycopeptides which had been depleted of I- and i-antigen activities 1838:1914 These oligosaccharides were derived from meconium glycopeptides which had been depleted of I- and i-antigen activities. 2731547 2 22 theme acidic 259:264 arg1 oligosaccharides 266:281 Neutral and acidic oligosaccharides 247:281 Neutral and acidic oligosaccharides 247:281 Neutral and acidic oligosaccharides were released by alkaline borohydride treatment, purified by Biogel P-6 and fractionated by high-performance liquid chromatography. 2731547 4 23 gly disialylated 671:682 arg1 oligosaccharides 558:573 five neutral oligosaccharides 545:573 five neutral oligosaccharides 545:573 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 4 23 gly disialylated 671:682 arg1 oligosaccharides 684:699 three disialylated oligosaccharides 665:699 three disialylated oligosaccharides 665:699 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 1 24 theme linked 143:148 arg1 oligosaccharides 169:184 the major O-glycosidically linked neutral and acidic oligosaccharides 116:184 the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins 116:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 4 25 theme present 488:494 arg1 study 496:500 The present study 484:500 The present study 484:500 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 2 26 theme borohydride 309:319 arg1 treatment 321:329 alkaline borohydride treatment 300:329 alkaline borohydride treatment 300:329 Neutral and acidic oligosaccharides were released by alkaline borohydride treatment, purified by Biogel P-6 and fractionated by high-performance liquid chromatography. 2731547 5 27 theme intestinal 887:896 arg1 compounds 971:979 high molecular mass compounds 951:979 high molecular mass compounds with numerous carbohydrate chains of the mucin type 951:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 5 27 theme intestinal 887:896 arg1 glycoproteins 898:910 The intestinal glycoproteins 883:910 (formula; see text) The intestinal glycoproteins of human meconium 863:928 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 13 28 theme molecular 2314:2322 arg1 mass 2324:2327 low molecular mass 2310:2327 several low molecular mass oligosaccharides of different size and composition 2302:2378 Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. 2731547 1 29 theme oligosaccharides 169:184 arg1 structure 103:111 The structure 99:111 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins 99:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 6 30 theme membrane-associated 1151:1169 arg1 antigens 1171:1178 membrane-associated antigens 1151:1178 membrane-associated antigens 1151:1178 These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. 2731547 9 31 theme acid 1704:1707 arg1 hydrolysis 1709:1718 mild acid hydrolysis 1699:1718 mild acid hydrolysis 1699:1718 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 7 32 attach derived 1301:1307 arg1 catabolism 1314:1323 catabolism 1314:1323 catabolism of O- and N-glycans accumulating in new born meconium 1314:1377 A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. 2731547 7 32 attach derived 1301:1307 arg2 oligosaccharides 1284:1299 fifteen free oligosaccharides 1271:1299 fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium 1271:1377 A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. 2731547 7 33 theme new 1361:1363 arg1 meconium 1370:1377 new born meconium 1361:1377 new born meconium 1361:1377 A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. 2731547 0 34 gly glycoproteins 84:96 arg1 glycoproteins 84:96 human meconium glycoproteins 69:96 human meconium glycoproteins 69:96 Structures of O-glycosidically linked oligosaccharides isolated from human meconium glycoproteins. 2731547 13 35 theme several 2302:2308 arg1 oligosaccharides 2329:2344 several low molecular mass oligosaccharides 2302:2344 several low molecular mass oligosaccharides of different size and composition 2302:2378 Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. 2731547 4 36 theme oligosaccharides 558:573 arg1 analysis 533:540 the primary structural analysis 510:540 the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy 510:800 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 8 37 theme resolution 1502:1511 arg1 spectroscopy 1520:1531 high resolution 1H-NMR spectroscopy 1497:1531 high resolution 1H-NMR spectroscopy analysis 1497:1540 In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. 2731547 10 38 theme meconium 1838:1845 arg1 glycopeptides 1847:1859 meconium glycopeptides 1838:1859 meconium glycopeptides which had been depleted of I- and i-antigen activities 1838:1914 These oligosaccharides were derived from meconium glycopeptides which had been depleted of I- and i-antigen activities. 2731547 5 39 theme high 951:954 arg1 compounds 971:979 high molecular mass compounds 951:979 high molecular mass compounds with numerous carbohydrate chains of the mucin type 951:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 5 39 theme high 951:954 arg1 glycoproteins 898:910 The intestinal glycoproteins 883:910 (formula; see text) The intestinal glycoproteins of human meconium 863:928 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 9 40 theme meconium 1758:1765 arg1 samples 1767:1773 meconium samples 1758:1773 meconium samples of group O secretors 1758:1794 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 8 41 theme spectroscopy 1520:1531 arg1 analysis 1533:1540 high resolution 1H-NMR spectroscopy analysis 1497:1540 high resolution 1H-NMR spectroscopy analysis 1497:1540 In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. 2731547 5 42 theme mass 966:969 arg1 compounds 971:979 high molecular mass compounds 951:979 high molecular mass compounds with numerous carbohydrate chains of the mucin type 951:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 5 42 theme mass 966:969 arg1 glycoproteins 898:910 The intestinal glycoproteins 883:910 (formula; see text) The intestinal glycoproteins of human meconium 863:928 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 1 43 theme major 120:124 arg1 oligosaccharides 169:184 the major O-glycosidically linked neutral and acidic oligosaccharides 116:184 the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins 116:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 1 44 theme acidic 162:167 arg1 oligosaccharides 169:184 the major O-glycosidically linked neutral and acidic oligosaccharides 116:184 the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins 116:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 4 45 theme disialylated 671:682 arg1 oligosaccharides 558:573 five neutral oligosaccharides 545:573 five neutral oligosaccharides 545:573 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 4 45 theme disialylated 671:682 arg1 oligosaccharides 684:699 three disialylated oligosaccharides 665:699 three disialylated oligosaccharides 665:699 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 5 46 with compounds 971:979 arg1 chains 1008:1013 numerous carbohydrate chains 986:1013 numerous carbohydrate chains of the mucin type 986:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 14 47 theme mass 2527:2530 arg1 FAB-MS 2546:2551 FAB-MS 2546:2551 FAB-MS 2546:2551 Using methylation analysis, 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry (FAB-MS), we propose the primary structure for 19 major oligosaccharides. 2731547 14 47 theme mass 2527:2530 arg1 spectrometry 2532:2543 fast-atom-bombardment mass spectrometry 2505:2543 fast-atom-bombardment mass spectrometry (FAB-MS) 2505:2552 Using methylation analysis, 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry (FAB-MS), we propose the primary structure for 19 major oligosaccharides. 2731547 0 48 theme oligosaccharides 38:53 arg1 Structures 0:9 Structures 0:9 Structures of O-glycosidically linked oligosaccharides 0:53 Structures of O-glycosidically linked oligosaccharides isolated from human meconium glycoproteins. 2731547 5 49 theme meconium 921:928 arg1 compounds 971:979 high molecular mass compounds 951:979 high molecular mass compounds with numerous carbohydrate chains of the mucin type 951:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 5 49 theme meconium 921:928 arg1 glycoproteins 898:910 The intestinal glycoproteins 883:910 (formula; see text) The intestinal glycoproteins of human meconium 863:928 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 9 50 theme O 1784:1784 arg1 secretors 1786:1794 group O secretors 1778:1794 group O secretors 1778:1794 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 3 51 theme acidic 459:464 arg1 oligosaccharides 466:481 30 acidic oligosaccharides 456:481 30 acidic oligosaccharides 456:481 This approach resulted in 50 neutral and 30 acidic oligosaccharides. 2731547 0 52 theme meconium 75:82 arg1 glycoproteins 84:96 human meconium glycoproteins 69:96 human meconium glycoproteins 69:96 Structures of O-glycosidically linked oligosaccharides isolated from human meconium glycoproteins. 2731547 11 53 gly glycoproteins 2038:2050 arg1 glycoproteins 2038:2050 human meconium glycoproteins 2023:2050 human meconium glycoproteins 2023:2050 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 7 54 theme oligosaccharides 1284:1299 arg1 structure 1258:1266 the structure 1254:1266 the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium 1254:1377 A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. 2731547 4 55 theme monosulfated 632:643 arg1 oligosaccharides 558:573 five neutral oligosaccharides 545:573 five neutral oligosaccharides 545:573 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 4 55 theme monosulfated 632:643 arg1 oligosaccharide 645:659 one monosialylated monosulfated oligosaccharide 613:659 one monosialylated monosulfated oligosaccharide 613:659 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 2 56 theme Neutral 247:253 arg1 oligosaccharides 266:281 Neutral and acidic oligosaccharides 247:281 Neutral and acidic oligosaccharides 247:281 Neutral and acidic oligosaccharides were released by alkaline borohydride treatment, purified by Biogel P-6 and fractionated by high-performance liquid chromatography. 2731547 9 57 gly glycoproteins 1572:1584 arg1 glycoproteins 1572:1584 O-glycosidically linked glycoproteins 1548:1584 O-glycosidically linked glycoproteins 1548:1584 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 2 58 theme liquid 392:397 arg1 chromatography 399:412 high-performance liquid chromatography 375:412 high-performance liquid chromatography 375:412 Neutral and acidic oligosaccharides were released by alkaline borohydride treatment, purified by Biogel P-6 and fractionated by high-performance liquid chromatography. 2731547 4 59 theme fast-atom-bombardment 721:741 arg1 analysis 761:768 fast-atom-bombardment mass spectrometry analysis 721:768 fast-atom-bombardment mass spectrometry analysis 721:768 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 14 60 theme fast-atom-bombardment 2505:2525 arg1 FAB-MS 2546:2551 FAB-MS 2546:2551 FAB-MS 2546:2551 Using methylation analysis, 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry (FAB-MS), we propose the primary structure for 19 major oligosaccharides. 2731547 14 60 theme fast-atom-bombardment 2505:2525 arg1 spectrometry 2532:2543 fast-atom-bombardment mass spectrometry 2505:2543 fast-atom-bombardment mass spectrometry (FAB-MS) 2505:2552 Using methylation analysis, 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry (FAB-MS), we propose the primary structure for 19 major oligosaccharides. 2731547 0 61 theme human 69:73 arg1 glycoproteins 84:96 human meconium glycoproteins 69:96 human meconium glycoproteins 69:96 Structures of O-glycosidically linked oligosaccharides isolated from human meconium glycoproteins. 2731547 4 62 theme spectrometry 748:759 arg1 analysis 761:768 fast-atom-bombardment mass spectrometry analysis 721:768 fast-atom-bombardment mass spectrometry analysis 721:768 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 9 63 theme linked 1565:1570 arg1 glycoproteins 1572:1584 O-glycosidically linked glycoproteins 1548:1584 O-glycosidically linked glycoproteins 1548:1584 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 0 64 link linked 31:36 arg1 oligosaccharides 38:53 O-glycosidically linked oligosaccharides 14:53 O-glycosidically linked oligosaccharides 14:53 Structures of O-glycosidically linked oligosaccharides isolated from human meconium glycoproteins. 2731547 5 65 theme following 807:815 arg1 structure 817:825 The following structure 803:825 The following structure 803:825 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 2 66 theme Biogel 344:349 arg1 P-6 351:353 Biogel P-6 344:353 Biogel P-6 344:353 Neutral and acidic oligosaccharides were released by alkaline borohydride treatment, purified by Biogel P-6 and fractionated by high-performance liquid chromatography. 2731547 13 67 theme linkage 2411:2417 arg1 position 2419:2426 linkage position 2411:2426 linkage position 2411:2426 Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. 2731547 9 68 link linked 1565:1570 arg1 glycoproteins 1572:1584 O-glycosidically linked glycoproteins 1548:1584 O-glycosidically linked glycoproteins 1548:1584 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 14 69 theme methylation 2459:2469 arg1 analysis 2471:2478 methylation analysis 2459:2478 methylation analysis 2459:2478 Using methylation analysis, 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry (FAB-MS), we propose the primary structure for 19 major oligosaccharides. 2731547 4 70 gly monosialylated 580:593 arg1 oligosaccharides 558:573 five neutral oligosaccharides 545:573 five neutral oligosaccharides 545:573 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 4 70 gly monosialylated 580:593 arg1 oligosaccharides 595:610 ten monosialylated oligosaccharides 576:610 ten monosialylated oligosaccharides 576:610 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 1 71 theme human 200:204 arg1 glycoproteins 215:227 human meconium glycoproteins 200:227 human meconium glycoproteins 200:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 12 72 theme normal-phase 2250:2261 arg1 chromatography 2263:2276 normal-phase chromatography 2250:2276 normal-phase chromatography 2250:2276 The neutral fraction was further purified by normal-phase and reversed-phase chromatography while acidic fractions were fractionated only by normal-phase chromatography. 2731547 1 73 attach isolated 186:193 arg1 glycoproteins 215:227 human meconium glycoproteins 200:227 human meconium glycoproteins 200:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 1 73 attach isolated 186:193 arg2 oligosaccharides 169:184 the major O-glycosidically linked neutral and acidic oligosaccharides 116:184 the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins 116:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 12 74 theme acidic 2207:2212 arg1 fractions 2214:2222 acidic fractions 2207:2222 acidic fractions 2207:2222 The neutral fraction was further purified by normal-phase and reversed-phase chromatography while acidic fractions were fractionated only by normal-phase chromatography. 2731547 6 75 theme group 1121:1125 arg1 activities 1127:1136 multiple blood group activities 1106:1136 multiple blood group activities 1106:1136 These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. 2731547 11 76 theme human 2023:2027 arg1 glycoproteins 2038:2050 human meconium glycoproteins 2023:2050 human meconium glycoproteins 2023:2050 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 6 77 theme multiple 1106:1113 arg1 activities 1127:1136 multiple blood group activities 1106:1136 multiple blood group activities 1106:1136 These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. 2731547 4 78 theme structural 522:531 arg1 analysis 533:540 the primary structural analysis 510:540 the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy 510:800 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 5 79 theme numerous 986:993 arg1 chains 1008:1013 numerous carbohydrate chains 986:1013 numerous carbohydrate chains of the mucin type 986:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 4 80 theme 1H-NMR 782:787 arg1 spectroscopy 789:800 400-MHz 1H-NMR spectroscopy 774:800 400-MHz 1H-NMR spectroscopy 774:800 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 9 81 theme major 1642:1646 arg1 monosaccharides 1648:1662 nine major monosaccharides 1637:1662 nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors 1637:1794 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 6 82 theme carbohydrate 1068:1079 arg1 structures 1081:1090 carbohydrate structures 1068:1090 carbohydrate structures which express multiple blood group activities 1068:1136 These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. 2731547 11 83 theme glycoproteins 2038:2050 arg1 degradation 2008:2018 alkaline borohydride degradation 1987:2018 alkaline borohydride degradation of human meconium glycoproteins 1987:2050 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 13 84 theme size 2359:2362 arg1 oligosaccharides 2329:2344 several low molecular mass oligosaccharides 2302:2344 several low molecular mass oligosaccharides of different size and composition 2302:2378 Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. 2731547 1 85 theme neutral 150:156 arg1 oligosaccharides 169:184 the major O-glycosidically linked neutral and acidic oligosaccharides 116:184 the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins 116:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 5 86 dep see 873:875 arg1 formula 864:870 formula 864:870 formula 864:870 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 14 87 theme major 2595:2599 arg1 oligosaccharides 2601:2616 19 major oligosaccharides 2592:2616 19 major oligosaccharides 2592:2616 Using methylation analysis, 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry (FAB-MS), we propose the primary structure for 19 major oligosaccharides. 2731547 11 88 theme acidic 1943:1948 arg1 [8 1926:1927 [8 1926:1927 [8 1926:1927 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 11 88 theme acidic 1943:1948 arg1 oligosaccharide-alditols 1950:1973 neutral and acidic oligosaccharide-alditols 1931:1973 neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins 1931:2050 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 13 89 theme composition 2368:2378 arg1 oligosaccharides 2329:2344 several low molecular mass oligosaccharides 2302:2344 several low molecular mass oligosaccharides of different size and composition 2302:2378 Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. 2731547 2 90 theme alkaline 300:307 arg1 treatment 321:329 alkaline borohydride treatment 300:329 alkaline borohydride treatment 300:329 Neutral and acidic oligosaccharides were released by alkaline borohydride treatment, purified by Biogel P-6 and fractionated by high-performance liquid chromatography. 2731547 4 91 gly monosialylated 617:630 arg1 oligosaccharides 558:573 five neutral oligosaccharides 545:573 five neutral oligosaccharides 545:573 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 4 91 gly monosialylated 617:630 arg1 oligosaccharide 645:659 one monosialylated monosulfated oligosaccharide 613:659 one monosialylated monosulfated oligosaccharide 613:659 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 5 92 theme type 1028:1031 arg1 chains 1008:1013 numerous carbohydrate chains 986:1013 numerous carbohydrate chains of the mucin type 986:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 4 93 theme monosialylated 580:593 arg1 oligosaccharides 558:573 five neutral oligosaccharides 545:573 five neutral oligosaccharides 545:573 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 4 93 theme monosialylated 580:593 arg1 oligosaccharides 595:610 ten monosialylated oligosaccharides 576:610 ten monosialylated oligosaccharides 576:610 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 11 94 theme neutral 1931:1937 arg1 [8 1926:1927 [8 1926:1927 [8 1926:1927 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 11 94 theme neutral 1931:1937 arg1 oligosaccharide-alditols 1950:1973 neutral and acidic oligosaccharide-alditols 1931:1973 neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins 1931:2050 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 7 95 theme born 1365:1368 arg1 meconium 1370:1377 new born meconium 1361:1377 new born meconium 1361:1377 A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. 2731547 13 96 theme mass 2324:2327 arg1 oligosaccharides 2329:2344 several low molecular mass oligosaccharides 2302:2344 several low molecular mass oligosaccharides of different size and composition 2302:2378 Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. 2731547 1 97 link linked 143:148 arg1 oligosaccharides 169:184 the major O-glycosidically linked neutral and acidic oligosaccharides 116:184 the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins 116:227 The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. 2731547 9 98 theme mild 1699:1702 arg1 hydrolysis 1709:1718 mild acid hydrolysis 1699:1718 mild acid hydrolysis 1699:1718 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 14 99 theme primary 2570:2576 arg1 structure 2578:2586 the primary structure 2566:2586 the primary structure for 19 major oligosaccharides 2566:2616 Using methylation analysis, 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry (FAB-MS), we propose the primary structure for 19 major oligosaccharides. 2731547 11 100 theme alkaline 1987:1994 arg1 borohydride 1996:2006 alkaline borohydride 1987:2006 alkaline borohydride degradation of human meconium glycoproteins 1987:2050 Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. 2731547 12 101 theme normal-phase 2154:2165 arg1 chromatography 2186:2199 normal-phase and reversed-phase chromatography 2154:2199 chromatography 2186:2199 The neutral fraction was further purified by normal-phase and reversed-phase chromatography while acidic fractions were fractionated only by normal-phase chromatography. 2731547 4 102 theme neutral 550:556 arg1 oligosaccharides 558:573 five neutral oligosaccharides 545:573 five neutral oligosaccharides 545:573 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 4 102 theme neutral 550:556 arg1 oligosaccharide 645:659 one monosialylated monosulfated oligosaccharide 613:659 one monosialylated monosulfated oligosaccharide 613:659 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 4 102 theme neutral 550:556 arg1 oligosaccharides 595:610 ten monosialylated oligosaccharides 576:610 ten monosialylated oligosaccharides 576:610 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 4 102 theme neutral 550:556 arg1 oligosaccharides 684:699 three disialylated oligosaccharides 665:699 three disialylated oligosaccharides 665:699 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 8 103 theme thirteen 1477:1484 arg1 description 1462:1472 the description 1458:1472 the description of thirteen of them 1458:1492 In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. 2731547 10 104 theme I- 1888:1889 arg1 activities 1905:1914 I- and i-antigen activities 1888:1914 I- and i-antigen activities 1888:1914 These oligosaccharides were derived from meconium glycopeptides which had been depleted of I- and i-antigen activities. 2731547 7 105 theme N-glycans 1335:1343 arg1 catabolism 1314:1323 catabolism 1314:1323 catabolism of O- and N-glycans accumulating in new born meconium 1314:1377 A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. 2731547 12 106 theme neutral 2113:2119 arg1 fraction 2121:2128 The neutral fraction 2109:2128 The neutral fraction 2109:2128 The neutral fraction was further purified by normal-phase and reversed-phase chromatography while acidic fractions were fractionated only by normal-phase chromatography. 2731547 9 107 theme base-borohydride 1724:1739 arg1 degradation 1741:1751 base-borohydride degradation 1724:1751 base-borohydride degradation 1724:1751 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 5 108 gly glycoproteins 898:910 arg1 compounds 971:979 high molecular mass compounds 951:979 high molecular mass compounds with numerous carbohydrate chains of the mucin type 951:1031 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 5 108 gly glycoproteins 898:910 arg1 glycoproteins 898:910 The intestinal glycoproteins 883:910 (formula; see text) The intestinal glycoproteins of human meconium 863:928 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 7 109 theme O- 1328:1329 arg1 catabolism 1314:1323 catabolism 1314:1323 catabolism of O- and N-glycans accumulating in new born meconium 1314:1377 A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. 2731547 13 110 theme low 2310:2312 arg1 mass 2324:2327 low molecular mass 2310:2327 several low molecular mass oligosaccharides of different size and composition 2302:2378 Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. 2731547 8 111 theme high 1497:1500 arg1 spectroscopy 1520:1531 high resolution 1H-NMR spectroscopy 1497:1531 high resolution 1H-NMR spectroscopy analysis 1497:1540 In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. 2731547 0 112 theme linked 31:36 arg1 oligosaccharides 38:53 O-glycosidically linked oligosaccharides 14:53 O-glycosidically linked oligosaccharides 14:53 Structures of O-glycosidically linked oligosaccharides isolated from human meconium glycoproteins. 2731547 8 113 with glycoasparagines 1436:1451 arg1 description 1462:1472 the description 1458:1472 the description of thirteen of them 1458:1492 In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. 2731547 8 114 theme 1H-NMR 1513:1518 arg1 spectroscopy 1520:1531 high resolution 1H-NMR spectroscopy 1497:1531 high resolution 1H-NMR spectroscopy analysis 1497:1540 In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. 2731547 5 115 theme human 915:919 arg1 meconium 921:928 human meconium 915:928 human meconium 915:928 The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. 2731547 9 116 theme group 1778:1782 arg1 secretors 1786:1794 group O secretors 1778:1794 group O secretors 1778:1794 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 6 117 theme hybridoma 1195:1203 arg1 antibodies 1205:1214 hybridoma antibodies [1-4] 1195:1220 hybridoma antibodies [1-4] 1195:1220 These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. 2731547 4 118 theme monosialylated 617:630 arg1 oligosaccharides 558:573 five neutral oligosaccharides 545:573 five neutral oligosaccharides 545:573 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 4 118 theme monosialylated 617:630 arg1 oligosaccharide 645:659 one monosialylated monosulfated oligosaccharide 613:659 one monosialylated monosulfated oligosaccharide 613:659 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 9 119 dep established 1607:1617 arg1 [7 1603:1604 [7 1603:1604 [7 1603:1604 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 7 120 theme free 1279:1282 arg1 oligosaccharides 1284:1299 fifteen free oligosaccharides 1271:1299 fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium 1271:1377 A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. 2731547 9 121 theme secretors 1786:1794 arg1 samples 1767:1773 meconium samples 1758:1773 meconium samples of group O secretors 1758:1794 From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. 2731547 10 122 theme i-antigen 1895:1903 arg1 activities 1905:1914 I- and i-antigen activities 1888:1914 I- and i-antigen activities 1888:1914 These oligosaccharides were derived from meconium glycopeptides which had been depleted of I- and i-antigen activities. 2731547 10 123 attach derived 1825:1831 arg1 glycopeptides 1847:1859 meconium glycopeptides 1838:1859 meconium glycopeptides which had been depleted of I- and i-antigen activities 1838:1914 These oligosaccharides were derived from meconium glycopeptides which had been depleted of I- and i-antigen activities. 2731547 10 123 attach derived 1825:1831 arg2 oligosaccharides 1803:1818 These oligosaccharides 1797:1818 These oligosaccharides 1797:1818 These oligosaccharides were derived from meconium glycopeptides which had been depleted of I- and i-antigen activities. 2731547 4 124 theme mass 743:746 arg1 analysis 761:768 fast-atom-bombardment mass spectrometry analysis 721:768 fast-atom-bombardment mass spectrometry analysis 721:768 The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. 2731547 8 125 theme them 1489:1492 arg1 them 1489:1492 them 1489:1492 them 1489:1492 In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. 2731547 8 125 theme them 1489:1492 arg1 thirteen 1477:1484 thirteen 1477:1484 thirteen 1477:1484 In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. 2731547 2 126 theme high-performance 375:390 arg1 chromatography 399:412 high-performance liquid chromatography 375:412 high-performance liquid chromatography 375:412 Neutral and acidic oligosaccharides were released by alkaline borohydride treatment, purified by Biogel P-6 and fractionated by high-performance liquid chromatography. 2731547 13 127 theme anomer 2431:2436 arg1 configuration 2438:2450 anomer configuration 2431:2450 anomer configuration 2431:2450 Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. 2731547 8 128 dep extended 1424:1431 arg1 [6 1398:1399 [6 1398:1399 [6 1398:1399 In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. 6468389 1 0 theme borohydride 349:359 arg1 treatment 361:369 alkaline borohydride treatment 340:369 alkaline borohydride treatment 340:369 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 3 1 theme 1H-NMR 572:577 arg1 spectroscopy 579:590 500-MHz 1H-NMR spectroscopy 564:590 500-MHz 1H-NMR spectroscopy 564:590 Twenty oligosaccharide structures were characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 6468389 6 2 theme oligosaccharides 935:950 arg1 pool 919:922 this pool 914:922 this pool of neutral oligosaccharides 914:950 127, 7-20], when paper-chromatographic fractionation of this pool of neutral oligosaccharides was employed. 6468389 7 3 theme pentasaccharide 1037:1051 arg1 alditols 1072:1079 another seven pentasaccharide and hexasaccharide alditols 1023:1079 another seven pentasaccharide and hexasaccharide alditols 1023:1079 High-performance liquid chromatography enabled to obtain another seven pentasaccharide and hexasaccharide alditols; the largest-size representatives are: (Formula see text). 6468389 7 4 theme largest-size 1086:1097 arg1 representatives 1099:1113 the largest-size representatives 1082:1113 the largest-size representatives 1082:1113 High-performance liquid chromatography enabled to obtain another seven pentasaccharide and hexasaccharide alditols; the largest-size representatives are: (Formula see text). 6468389 6 5 theme neutral 927:933 arg1 oligosaccharides 935:950 neutral oligosaccharides 927:950 neutral oligosaccharides 927:950 127, 7-20], when paper-chromatographic fractionation of this pool of neutral oligosaccharides was employed. 6468389 0 6 theme heterogeneity 103:115 arg1 characterization 8:23 Further characterization 0:23 Further characterization 0:23 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 1 7 attach released 288:295 arg2 chains 276:281 the carbohydrate chains 259:281 the carbohydrate chains 259:281 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 1 7 attach released 288:295 arg1 mucins 204:209 bronchial mucins 194:209 bronchial mucins of cystic fibrosis patients with blood group O 194:256 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 1 8 theme carbohydrate 263:274 arg1 chains 276:281 the carbohydrate chains 259:281 the carbohydrate chains 259:281 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 3 9 with conjunction 595:605 arg1 analysis 618:625 sugar analysis 612:625 sugar analysis 612:625 Twenty oligosaccharide structures were characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 6468389 8 10 theme bronchial 1261:1269 arg1 mucins 1271:1276 bronchial mucins 1261:1276 bronchial mucins 1261:1276 Thereby, this approach afforded deeper insight into the structural heterogeneity displayed by the carbohydrate chains of bronchial mucins. 6468389 6 11 theme pool 919:922 arg1 fractionation 897:909 paper-chromatographic fractionation 875:909 paper-chromatographic fractionation of this pool of neutral oligosaccharides 875:950 127, 7-20], when paper-chromatographic fractionation of this pool of neutral oligosaccharides was employed. 6468389 7 12 theme High-performance 966:981 arg1 chromatography 990:1003 High-performance liquid chromatography 966:1003 High-performance liquid chromatography 966:1003 High-performance liquid chromatography enabled to obtain another seven pentasaccharide and hexasaccharide alditols; the largest-size representatives are: (Formula see text). 6468389 2 13 theme neutral 450:456 arg1 oligosaccharides 458:473 neutral oligosaccharides 450:473 neutral oligosaccharides 450:473 Application of high-performance liquid chromatography directly on the pool of neutral oligosaccharides afforded 23 fractions. 6468389 8 14 theme carbohydrate 1238:1249 arg1 chains 1251:1256 the carbohydrate chains 1234:1256 the carbohydrate chains of bronchial mucins 1234:1276 Thereby, this approach afforded deeper insight into the structural heterogeneity displayed by the carbohydrate chains of bronchial mucins. 6468389 6 15 dep 127 858:860 arg1 7-20 863:866 7-20 863:866 7-20 863:866 127, 7-20], when paper-chromatographic fractionation of this pool of neutral oligosaccharides was employed. 6468389 3 16 theme sugar 612:616 arg1 analysis 618:625 sugar analysis 612:625 sugar analysis 612:625 Twenty oligosaccharide structures were characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 6468389 7 17 theme liquid 983:988 arg1 chromatography 990:1003 High-performance liquid chromatography 966:1003 High-performance liquid chromatography 966:1003 High-performance liquid chromatography enabled to obtain another seven pentasaccharide and hexasaccharide alditols; the largest-size representatives are: (Formula see text). 6468389 2 18 from Application 372:382 arg1 pool 442:445 the pool 438:445 the pool of neutral oligosaccharides 438:473 Application of high-performance liquid chromatography directly on the pool of neutral oligosaccharides afforded 23 fractions. 6468389 1 19 theme bronchial 194:202 arg1 mucins 204:209 bronchial mucins 194:209 bronchial mucins of cystic fibrosis patients with blood group O 194:256 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 0 20 theme Further 0:6 arg1 characterization 8:23 Further characterization 0:23 Further characterization 0:23 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 7 21 theme hexasaccharide 1057:1070 arg1 alditols 1072:1079 another seven pentasaccharide and hexasaccharide alditols 1023:1079 another seven pentasaccharide and hexasaccharide alditols 1023:1079 High-performance liquid chromatography enabled to obtain another seven pentasaccharide and hexasaccharide alditols; the largest-size representatives are: (Formula see text). 6468389 2 22 theme chromatography 411:424 arg1 Application 372:382 Application 372:382 Application of high-performance liquid chromatography directly on the pool of neutral oligosaccharides 372:473 Application of high-performance liquid chromatography directly on the pool of neutral oligosaccharides afforded 23 fractions. 6468389 0 23 theme neutral 134:140 arg1 chains 155:160 the neutral carbohydrate chains 130:160 the neutral carbohydrate chains of human bronchial mucins 130:186 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 2 24 theme oligosaccharides 458:473 arg1 pool 442:445 the pool 438:445 the pool of neutral oligosaccharides 438:473 Application of high-performance liquid chromatography directly on the pool of neutral oligosaccharides afforded 23 fractions. 6468389 1 25 with patients 230:237 arg1 O 256:256 blood group O 244:256 blood group O 244:256 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 1 26 theme cystic 214:219 arg1 fibrosis 221:228 cystic fibrosis 214:228 cystic fibrosis patients with blood group O 214:256 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 0 27 theme combined 31:38 arg1 approach 86:93 a combined high-performance liquid chromatography/1H-NMR approach 29:93 a combined high-performance liquid chromatography/1H-NMR approach 29:93 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 6 28 theme paper-chromatographic 875:895 arg1 fractionation 897:909 paper-chromatographic fractionation 875:909 paper-chromatographic fractionation of this pool of neutral oligosaccharides 875:950 127, 7-20], when paper-chromatographic fractionation of this pool of neutral oligosaccharides was employed. 6468389 1 29 theme fibrosis 221:228 arg1 patients 230:237 cystic fibrosis patients 214:237 cystic fibrosis patients with blood group O 214:256 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 8 30 theme deeper 1172:1177 arg1 insight 1179:1185 deeper insight 1172:1185 deeper insight into the structural heterogeneity displayed by the carbohydrate chains of bronchial mucins 1172:1276 Thereby, this approach afforded deeper insight into the structural heterogeneity displayed by the carbohydrate chains of bronchial mucins. 6468389 0 31 theme carbohydrate 142:153 arg1 chains 155:160 the neutral carbohydrate chains 130:160 the neutral carbohydrate chains of human bronchial mucins 130:186 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 4 32 theme bronchial 692:700 arg1 mucins 702:707 human bronchial mucins 686:707 human bronchial mucins [Van Halbeek, H., Dorland, L., Vliegenthart, J. F. G., Hull, W. E., Lamblin, G., Lhermitte, M., Boersma, A., and Roussel, P. (1982) Eur 686:843 Thirteen among these had been revealed before to occur in human bronchial mucins [Van Halbeek, H., Dorland, L., Vliegenthart, J. F. G., Hull, W. E., Lamblin, G., Lhermitte, M., Boersma, A., and Roussel, P. (1982) Eur. 6468389 1 33 theme patients 230:237 arg1 mucins 204:209 bronchial mucins 194:209 bronchial mucins of cystic fibrosis patients with blood group O 194:256 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 0 34 theme liquid 57:62 arg1 approach 86:93 a combined high-performance liquid chromatography/1H-NMR approach 29:93 a combined high-performance liquid chromatography/1H-NMR approach 29:93 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 0 35 theme human 165:169 arg1 mucins 181:186 human bronchial mucins 165:186 human bronchial mucins 165:186 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 2 36 from chromatography 411:424 arg1 pool 442:445 the pool 438:445 the pool of neutral oligosaccharides 438:473 Application of high-performance liquid chromatography directly on the pool of neutral oligosaccharides afforded 23 fractions. 6468389 8 37 theme mucins 1271:1276 arg1 chains 1251:1256 the carbohydrate chains 1234:1256 the carbohydrate chains of bronchial mucins 1234:1276 Thereby, this approach afforded deeper insight into the structural heterogeneity displayed by the carbohydrate chains of bronchial mucins. 6468389 0 38 theme high-performance 40:55 arg1 approach 86:93 a combined high-performance liquid chromatography/1H-NMR approach 29:93 a combined high-performance liquid chromatography/1H-NMR approach 29:93 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 1 39 theme oligosaccharide-alditols 312:335 arg1 form 304:307 the form 300:307 the form of oligosaccharide-alditols 300:335 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 4 40 dep mucins 702:707 arg1 Eur 841:843 Eur 841:843 Eur 841:843 Thirteen among these had been revealed before to occur in human bronchial mucins [Van Halbeek, H., Dorland, L., Vliegenthart, J. F. G., Hull, W. E., Lamblin, G., Lhermitte, M., Boersma, A., and Roussel, P. (1982) Eur. 6468389 3 41 theme 500-MHz 564:570 arg1 spectroscopy 579:590 500-MHz 1H-NMR spectroscopy 564:590 500-MHz 1H-NMR spectroscopy 564:590 Twenty oligosaccharide structures were characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 6468389 0 42 theme mucins 181:186 arg1 chains 155:160 the neutral carbohydrate chains 130:160 the neutral carbohydrate chains of human bronchial mucins 130:186 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 0 43 theme bronchial 171:179 arg1 mucins 181:186 human bronchial mucins 165:186 human bronchial mucins 165:186 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 1 44 theme blood 244:248 arg1 O 256:256 blood group O 244:256 blood group O 244:256 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 3 45 theme oligosaccharide 505:519 arg1 structures 521:530 Twenty oligosaccharide structures 498:530 Twenty oligosaccharide structures 498:530 Twenty oligosaccharide structures were characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. 6468389 2 46 from pool 442:445 arg1 Application 372:382 Application 372:382 Application of high-performance liquid chromatography directly on the pool of neutral oligosaccharides 372:473 Application of high-performance liquid chromatography directly on the pool of neutral oligosaccharides afforded 23 fractions. 6468389 2 47 theme liquid 404:409 arg1 chromatography 411:424 high-performance liquid chromatography 387:424 high-performance liquid chromatography directly on the pool of neutral oligosaccharides 387:473 Application of high-performance liquid chromatography directly on the pool of neutral oligosaccharides afforded 23 fractions. 6468389 8 48 theme structural 1196:1205 arg1 heterogeneity 1207:1219 the structural heterogeneity 1192:1219 the structural heterogeneity displayed by the carbohydrate chains of bronchial mucins 1192:1276 Thereby, this approach afforded deeper insight into the structural heterogeneity displayed by the carbohydrate chains of bronchial mucins. 6468389 1 49 theme group 250:254 arg1 O 256:256 blood group O 244:256 blood group O 244:256 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 0 50 theme chromatography/1H-NMR 64:84 arg1 approach 86:93 a combined high-performance liquid chromatography/1H-NMR approach 29:93 a combined high-performance liquid chromatography/1H-NMR approach 29:93 Further characterization, by a combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. 6468389 1 51 theme alkaline 340:347 arg1 treatment 361:369 alkaline borohydride treatment 340:369 alkaline borohydride treatment 340:369 From bronchial mucins of cystic fibrosis patients with blood group O, the carbohydrate chains were released in the form of oligosaccharide-alditols by alkaline borohydride treatment. 6468389 4 52 theme [Van 709:712 arg1 mucins 702:707 human bronchial mucins 686:707 human bronchial mucins [Van Halbeek, H., Dorland, L., Vliegenthart, J. F. G., Hull, W. E., Lamblin, G., Lhermitte, M., Boersma, A., and Roussel, P. (1982) Eur 686:843 Thirteen among these had been revealed before to occur in human bronchial mucins [Van Halbeek, H., Dorland, L., Vliegenthart, J. F. G., Hull, W. E., Lamblin, G., Lhermitte, M., Boersma, A., and Roussel, P. (1982) Eur. 6468389 2 53 theme high-performance 387:402 arg1 chromatography 411:424 high-performance liquid chromatography 387:424 high-performance liquid chromatography directly on the pool of neutral oligosaccharides 387:473 Application of high-performance liquid chromatography directly on the pool of neutral oligosaccharides afforded 23 fractions. 6468389 4 54 theme human 686:690 arg1 mucins 702:707 human bronchial mucins 686:707 human bronchial mucins [Van Halbeek, H., Dorland, L., Vliegenthart, J. F. G., Hull, W. E., Lamblin, G., Lhermitte, M., Boersma, A., and Roussel, P. (1982) Eur 686:843 Thirteen among these had been revealed before to occur in human bronchial mucins [Van Halbeek, H., Dorland, L., Vliegenthart, J. F. G., Hull, W. E., Lamblin, G., Lhermitte, M., Boersma, A., and Roussel, P. (1982) Eur. 2363690 0 0 theme subclass 76:83 arg1 proteins 85:92 human IgG subclass proteins 66:92 human IgG subclass proteins 66:92 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 2363690 4 1 dep Man 702:704 arg1 arms 742:745 arms 742:745 arms 742:745 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 0 2 theme IgG 72:74 arg1 proteins 85:92 human IgG subclass proteins 66:92 human IgG subclass proteins 66:92 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 2363690 4 3 theme alpha 728:732 arg1 Man 724:726 Man 724:726 Man(alpha 1----6) 724:740 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 4 3 theme alpha 728:732 arg1 1----6 734:739 alpha 1----6 728:739 alpha 1----6 728:739 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 4 4 theme carbohydrate 768:779 arg1 moieties 781:788 both Fc-localized carbohydrate moieties 750:788 both Fc-localized carbohydrate moieties 750:788 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 3 5 theme alpha 497:501 arg1 Man 493:495 Man 493:495 the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm 451:513 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 3 5 theme alpha 497:501 arg1 1----6 503:508 alpha 1----6 497:508 alpha 1----6 497:508 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 5 6 dep IgG2 987:990 arg1 proteins 1001:1008 proteins 1001:1008 proteins 1001:1008 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 3 7 from galactose 438:446 arg1 arm 511:513 the Man(alpha 1----6) arm 489:513 the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm 451:513 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 3 7 from galactose 438:446 arg1 arm 473:475 the Man(alpha 1----3) arm 451:475 the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm 451:513 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 4 8 theme previous 791:798 arg1 findings 800:807 previous findings 791:807 previous findings 791:807 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 1 9 theme human 164:168 arg1 paraproteins 174:185 18 human IgG paraproteins 161:185 18 human IgG paraproteins representing the four subclasses 161:218 Quantitative oligosaccharide profiles were determined for each of 18 human IgG paraproteins representing the four subclasses. 2363690 0 10 theme proteins 85:92 arg1 structures 52:61 the N-linked oligosaccharide structures 23:61 the N-linked oligosaccharide structures of human IgG subclass proteins 23:92 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 2363690 4 11 theme galactosylated 687:700 arg1 Man 702:704 Man 702:704 Man(alpha 1----3) 702:718 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 4 11 theme galactosylated 687:700 arg1 1----3 712:717 alpha 1----3 706:717 alpha 1----3 706:717 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 3 12 contain having 431:436 arg2 galactose 438:446 galactose 438:446 galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm 438:513 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 3 12 contain having 431:436 arg1 moieties 422:429 oligosaccharide moieties 406:429 oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm 406:513 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 4 13 theme alpha 706:710 arg1 Man 702:704 Man 702:704 Man(alpha 1----3) 702:718 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 4 13 theme alpha 706:710 arg1 1----3 712:717 alpha 1----3 706:717 alpha 1----3 706:717 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 1 14 theme IgG 170:172 arg1 paraproteins 174:185 18 human IgG paraproteins 161:185 18 human IgG paraproteins representing the four subclasses 161:218 Quantitative oligosaccharide profiles were determined for each of 18 human IgG paraproteins representing the four subclasses. 2363690 3 15 theme IgG3 357:360 arg1 proteins 362:369 The IgG2 and some IgG3 proteins 339:369 The IgG2 and some IgG3 proteins analysed 339:378 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 4 16 theme C 918:918 arg1 gamma 920:924 C gamma 2 918:926 the C gamma 2 domains 914:934 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 0 17 theme comparative 2:12 arg1 study 14:18 A comparative study 0:18 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 0:93 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 2363690 5 18 from present 976:982 arg1 IgG3 996:999 IgG3 996:999 IgG3 996:999 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 5 18 from present 976:982 arg1 IgG2 987:990 IgG2 987:990 IgG2 987:990 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 4 19 theme Fc-localized 755:766 arg1 moieties 781:788 both Fc-localized carbohydrate moieties 750:788 both Fc-localized carbohydrate moieties 750:788 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 3 20 theme IgG2 343:346 arg1 proteins 362:369 The IgG2 and some IgG3 proteins 339:369 The IgG2 and some IgG3 proteins analysed 339:378 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 3 21 theme moieties 422:429 arg1 predominance 390:401 a predominance 388:401 a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm 388:513 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 4 22 theme domains 928:934 arg1 space 905:909 the internal space 892:909 the internal space of the C gamma 2 domains 892:934 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 0 23 link N-linked 27:34 arg1 structures 52:61 the N-linked oligosaccharide structures 23:61 the N-linked oligosaccharide structures of human IgG subclass proteins 23:92 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 2363690 2 24 theme polyclonal 323:332 arg1 IgG 334:336 polyclonal IgG 323:336 polyclonal IgG 323:336 Each paraprotein exhibits a unique profile that may be substantially different from that observed for polyclonal IgG. 2363690 4 25 contain has 683:685 arg1 that 678:681 that 678:681 that 678:681 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 4 25 contain has 683:685 arg2 1----3 712:717 alpha 1----3 706:717 alpha 1----3 706:717 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 4 25 contain has 683:685 arg2 Man 702:704 Man 702:704 Man(alpha 1----3) 702:718 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 4 25 contain has 683:685 arg2 1----6 734:739 alpha 1----6 728:739 alpha 1----6 728:739 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 4 25 contain has 683:685 arg2 Man 724:726 Man 724:726 Man(alpha 1----6) 724:740 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 4 26 theme glycosylated 835:846 arg1 structures 848:857 such fully glycosylated structures 824:857 such fully glycosylated structures 824:857 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 1 27 theme Quantitative 95:106 arg1 profiles 124:131 Quantitative oligosaccharide profiles 95:131 Quantitative oligosaccharide profiles 95:131 Quantitative oligosaccharide profiles were determined for each of 18 human IgG paraproteins representing the four subclasses. 2363690 3 28 theme Man 567:569 arg1 arm 585:587 the Man(alpha 1----6) arm 563:587 the Man(alpha 1----6) arm 563:587 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 5 29 attach present 976:982 arg2 oligosaccharides 959:974 Unusual monoantennary oligosaccharides 937:974 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins 937:1008 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 5 29 attach present 976:982 arg1 IgG2 987:990 IgG2 987:990 IgG2 987:990 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 5 29 attach present 976:982 arg1 IgG3 996:999 IgG3 996:999 IgG3 996:999 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 1 30 theme oligosaccharide 108:122 arg1 profiles 124:131 Quantitative oligosaccharide profiles 95:131 Quantitative oligosaccharide profiles 95:131 Quantitative oligosaccharide profiles were determined for each of 18 human IgG paraproteins representing the four subclasses. 2363690 4 31 theme internal 896:903 arg1 space 905:909 the internal space 892:909 the internal space of the C gamma 2 domains 892:934 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 0 32 theme N-linked 27:34 arg1 structures 52:61 the N-linked oligosaccharide structures 23:61 the N-linked oligosaccharide structures of human IgG subclass proteins 23:92 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 2363690 4 33 gly glycosylated 835:846 arg1 structures 848:857 such fully glycosylated structures 824:857 such fully glycosylated structures 824:857 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 2 34 theme unique 249:254 arg1 different 290:298 different 290:298 different 290:298 Each paraprotein exhibits a unique profile that may be substantially different from that observed for polyclonal IgG. 2363690 2 34 theme unique 249:254 arg1 profile 256:262 a unique profile 247:262 a unique profile that may be substantially different from that observed for polyclonal IgG 247:336 Each paraprotein exhibits a unique profile that may be substantially different from that observed for polyclonal IgG. 2363690 3 35 theme alpha 459:463 arg1 Man 455:457 Man 455:457 the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm 451:513 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 3 35 theme alpha 459:463 arg1 1----3 465:470 alpha 1----3 459:470 alpha 1----3 459:470 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 3 36 theme Man 455:457 arg1 arm 473:475 the Man(alpha 1----3) arm 451:475 the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm 451:513 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 4 37 theme gamma 920:924 arg1 domains 928:934 the C gamma 2 domains 914:934 the C gamma 2 domains 914:934 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 5 38 from IgG3 996:999 arg1 present 976:982 present 976:982 present 976:982 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 3 39 theme oligosaccharide 406:420 arg1 moieties 422:429 oligosaccharide moieties 406:429 oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm 406:513 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 5 40 from IgG2 987:990 arg1 present 976:982 present 976:982 present 976:982 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 5 41 theme Unusual 937:943 arg1 oligosaccharides 959:974 Unusual monoantennary oligosaccharides 937:974 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins 937:1008 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 0 42 theme oligosaccharide 36:50 arg1 structures 52:61 the N-linked oligosaccharide structures 23:61 the N-linked oligosaccharide structures of human IgG subclass proteins 23:92 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 2363690 5 43 theme monoantennary 945:957 arg1 oligosaccharides 959:974 Unusual monoantennary oligosaccharides 937:974 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins 937:1008 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 3 44 theme Man 493:495 arg1 arm 511:513 the Man(alpha 1----6) arm 489:513 the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm 451:513 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 4 45 theme such 824:827 arg1 structures 848:857 such fully glycosylated structures 824:857 such fully glycosylated structures 824:857 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 5 46 theme present 976:982 arg1 oligosaccharides 959:974 Unusual monoantennary oligosaccharides 937:974 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins 937:1008 Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. 2363690 3 47 theme arm 585:587 arg1 galactosylation 544:558 galactosylation 544:558 galactosylation of the Man(alpha 1----6) arm 544:587 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 4 48 theme IgG4 653:656 arg1 protein 658:664 An IgG4 protein 650:664 An IgG4 protein 650:664 An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. 2363690 2 49 from that 305:308 arg1 different 290:298 different 290:298 different 290:298 Each paraprotein exhibits a unique profile that may be substantially different from that observed for polyclonal IgG. 2363690 2 49 from that 305:308 arg1 profile 256:262 a unique profile 247:262 a unique profile that may be substantially different from that observed for polyclonal IgG 247:336 Each paraprotein exhibits a unique profile that may be substantially different from that observed for polyclonal IgG. 2363690 0 50 theme human 66:70 arg1 proteins 85:92 human IgG subclass proteins 66:92 human IgG subclass proteins 66:92 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 2363690 3 51 theme alpha 571:575 arg1 arm 585:587 the Man(alpha 1----6) arm 563:587 the Man(alpha 1----6) arm 563:587 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 0 52 theme structures 52:61 arg1 study 14:18 A comparative study 0:18 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 0:93 A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. 2363690 3 53 theme polyclonal 634:643 arg1 IgG 645:647 polyclonal IgG 634:647 polyclonal IgG 634:647 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 2363690 3 54 theme 1----6 577:582 arg1 arm 585:587 the Man(alpha 1----6) arm 563:587 the Man(alpha 1----6) arm 563:587 The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. 3567160 0 0 theme pathological 82:93 arg1 G 110:110 human normal and pathological immunoglobulin G 65:110 human normal and pathological immunoglobulin G 65:110 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. 3567160 5 1 theme resonance 751:759 arg1 spectroscopy 761:772 High-resolution proton nuclear magnetic resonance spectroscopy 711:772 High-resolution proton nuclear magnetic resonance spectroscopy 711:772 High-resolution proton nuclear magnetic resonance spectroscopy was used along with chemical methods to determine the structures of the separated oligosaccharides. 3567160 1 2 theme pathological 162:173 arg1 IgG 193:195 IgG 193:195 IgG 193:195 The structures of oligosaccharides of normal and pathological immunoglobulin G (IgG) are reported. 3567160 1 2 theme pathological 162:173 arg1 G 190:190 immunoglobulin G 175:190 normal and pathological immunoglobulin G (IgG) 151:196 The structures of oligosaccharides of normal and pathological immunoglobulin G (IgG) are reported. 3567160 3 3 theme oligosaccharide 350:364 arg1 chains 366:371 the oligosaccharide chains 346:371 the oligosaccharide chains thus obtained 346:385 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 1 4 theme immunoglobulin 175:188 arg1 IgG 193:195 IgG 193:195 IgG 193:195 The structures of oligosaccharides of normal and pathological immunoglobulin G (IgG) are reported. 3567160 1 4 theme immunoglobulin 175:188 arg1 G 190:190 immunoglobulin G 175:190 normal and pathological immunoglobulin G (IgG) 151:196 The structures of oligosaccharides of normal and pathological immunoglobulin G (IgG) are reported. 3567160 6 5 theme biantennary 913:923 arg1 predominant 999:1009 predominant 999:1009 predominant 999:1009 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 6 5 theme biantennary 913:923 arg1 oligosaccharide 938:952 a biantennary complex-type oligosaccharide 911:952 a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) 911:994 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 0 6 theme G 110:110 arg1 oligosaccharides 45:60 the N-linked oligosaccharides 32:60 the N-linked oligosaccharides of human normal and pathological immunoglobulin G 32:110 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. 3567160 10 7 dep structure 1762:1770 arg1 see 1782:1784 see 1782:1784 see text 1782:1789 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 10 8 theme fucose 1715:1720 arg1 residue 1722:1728 a fucose residue 1713:1728 a fucose residue 1713:1728 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 4 9 theme oligosaccharides 639:654 arg1 kinds 630:634 the 16 kinds 623:634 the 16 kinds of oligosaccharides that have been suggested to exist in normal human IgG 623:708 It was possible to separate 15 out of the 16 kinds of oligosaccharides that have been suggested to exist in normal human IgG. 3567160 0 10 theme immunoglobulin 95:108 arg1 G 110:110 human normal and pathological immunoglobulin G 65:110 human normal and pathological immunoglobulin G 65:110 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. 3567160 9 11 theme oligosaccharides 1502:1517 arg1 fractions 1471:1479 the fractions 1467:1479 the fractions of fucose-containing oligosaccharides 1467:1517 We show that the fractions of fucose-containing oligosaccharides are markedly decreased in the heavy-chain disease protein Per. 3567160 5 12 theme High-resolution 711:725 arg1 resonance 751:759 High-resolution proton nuclear magnetic resonance 711:759 High-resolution proton nuclear magnetic resonance spectroscopy 711:772 High-resolution proton nuclear magnetic resonance spectroscopy was used along with chemical methods to determine the structures of the separated oligosaccharides. 3567160 10 13 theme biantennary 1661:1671 arg1 component 1646:1654 the major component 1636:1654 the major component 1636:1654 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 10 13 theme biantennary 1661:1671 arg1 oligosaccharide 1686:1700 a biantennary complex-type oligosaccharide 1659:1700 a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components 1659:1836 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 3 14 theme liquid 562:567 arg1 chromatography 569:582 reverse-phase high-performance liquid chromatography 531:582 reverse-phase high-performance liquid chromatography 531:582 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 8 15 from terminal 1444:1451 arg1 residues 1416:1423 one or two galactose residues 1395:1423 one or two galactose residues at the nonreducing terminal 1395:1451 It has been found that the most abundant species that exist in the pathological proteins analyzed in the present work lack one or two galactose residues at the nonreducing terminal. 3567160 6 16 theme oligosaccharides 1029:1044 arg1 kinds 1020:1024 four kinds 1015:1024 four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, 1015:1131 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 6 17 theme fucose 961:966 arg1 residue 968:974 a fucose residue 959:974 a fucose residue (formula; see text) 959:994 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 1 18 theme G 190:190 arg1 oligosaccharides 131:146 oligosaccharides 131:146 oligosaccharides of normal and pathological immunoglobulin G (IgG) 131:196 The structures of oligosaccharides of normal and pathological immunoglobulin G (IgG) are reported. 3567160 7 19 theme normal 1195:1200 arg1 IgG 1202:1204 normal IgG 1195:1204 normal IgG 1195:1204 The results obtained for normal IgG were compared with those obtained for three myeloma IgG proteins. 3567160 10 20 from oligosaccharide 1686:1700 arg1 paraprotein 1624:1634 this paraprotein 1619:1634 this paraprotein 1619:1634 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 10 21 dep see 1782:1784 arg1 Formula 1773:1779 Formula 1773:1779 Formula 1773:1779 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 3 22 theme derivatives 478:488 arg1 mixture 454:460 the mixture 450:460 the mixture of pyridylamino derivatives of the oligosaccharides 450:512 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 0 23 theme structural 12:21 arg1 study 23:27 Comparative structural study 0:27 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G 0:110 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. 3567160 3 24 theme chains 366:371 arg1 aminated 392:399 aminated 392:399 aminated 392:399 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 3 24 theme chains 366:371 arg1 ends 338:341 The reducing ends 325:341 The reducing ends of the oligosaccharide chains thus obtained 325:385 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 10 25 theme abundant 1818:1825 arg1 components 1827:1836 the most abundant components 1809:1836 the most abundant components 1809:1836 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 10 26 theme major 1640:1644 arg1 component 1646:1654 the major component 1636:1654 the major component 1636:1654 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 10 26 theme major 1640:1644 arg1 oligosaccharide 1686:1700 a biantennary complex-type oligosaccharide 1659:1700 a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components 1659:1836 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 6 27 with oligosaccharide 938:952 arg1 residue 968:974 a fucose residue 959:974 a fucose residue (formula; see text) 959:994 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 0 28 theme Comparative 0:10 arg1 study 23:27 Comparative structural study 0:27 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G 0:110 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. 3567160 0 29 link N-linked 36:43 arg1 oligosaccharides 45:60 the N-linked oligosaccharides 32:60 the N-linked oligosaccharides of human normal and pathological immunoglobulin G 32:110 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. 3567160 6 30 theme complex-type 925:936 arg1 predominant 999:1009 predominant 999:1009 predominant 999:1009 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 6 30 theme complex-type 925:936 arg1 oligosaccharide 938:952 a biantennary complex-type oligosaccharide 911:952 a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) 911:994 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 6 31 from IgG 907:909 arg1 predominant 999:1009 predominant 999:1009 predominant 999:1009 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 6 31 from IgG 907:909 arg1 oligosaccharide 938:952 a biantennary complex-type oligosaccharide 911:952 a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) 911:994 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 8 32 theme pathological 1339:1350 arg1 proteins 1352:1359 the pathological proteins 1335:1359 the pathological proteins analyzed in the present work 1335:1388 It has been found that the most abundant species that exist in the pathological proteins analyzed in the present work lack one or two galactose residues at the nonreducing terminal. 3567160 8 33 theme nonreducing 1432:1442 arg1 terminal 1444:1451 the nonreducing terminal 1428:1451 the nonreducing terminal 1428:1451 It has been found that the most abundant species that exist in the pathological proteins analyzed in the present work lack one or two galactose residues at the nonreducing terminal. 3567160 3 34 theme oligosaccharides 497:512 arg1 derivatives 478:488 pyridylamino derivatives 465:488 pyridylamino derivatives of the oligosaccharides 465:512 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 3 35 theme fluorescent 408:418 arg1 reagent 420:426 a fluorescent reagent 406:426 a fluorescent reagent 406:426 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 3 35 theme fluorescent 408:418 arg1 2-aminopyridine 429:443 2-aminopyridine 429:443 2-aminopyridine 429:443 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 9 36 theme heavy-chain 1549:1559 arg1 protein 1569:1575 the heavy-chain disease protein 1545:1575 the heavy-chain disease protein Per 1545:1579 We show that the fractions of fucose-containing oligosaccharides are markedly decreased in the heavy-chain disease protein Per. 3567160 8 37 theme galactose 1406:1414 arg1 residues 1416:1423 one or two galactose residues 1395:1423 one or two galactose residues at the nonreducing terminal 1395:1451 It has been found that the most abundant species that exist in the pathological proteins analyzed in the present work lack one or two galactose residues at the nonreducing terminal. 3567160 6 38 theme fucose 1116:1121 arg1 residues 1123:1130 fucose residues 1116:1130 fucose residues 1116:1130 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 0 39 theme N-linked 36:43 arg1 oligosaccharides 45:60 the N-linked oligosaccharides 32:60 the N-linked oligosaccharides of human normal and pathological immunoglobulin G 32:110 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. 3567160 4 40 theme normal 693:698 arg1 IgG 706:708 normal human IgG 693:708 normal human IgG 693:708 It was possible to separate 15 out of the 16 kinds of oligosaccharides that have been suggested to exist in normal human IgG. 3567160 10 41 theme components 1827:1836 arg1 components 1827:1836 the most abundant components 1809:1836 the most abundant components 1809:1836 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 10 41 theme components 1827:1836 arg1 one 1802:1804 one 1802:1804 one 1802:1804 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 9 42 theme fucose-containing 1484:1500 arg1 oligosaccharides 1502:1517 fucose-containing oligosaccharides 1484:1517 fucose-containing oligosaccharides 1484:1517 We show that the fractions of fucose-containing oligosaccharides are markedly decreased in the heavy-chain disease protein Per. 3567160 2 43 link Asparagine-linked 212:228 arg1 oligosaccharides 238:253 Asparagine-linked neutral oligosaccharides 212:253 Asparagine-linked neutral oligosaccharides 212:253 Asparagine-linked neutral oligosaccharides were released by N-oligosaccharide glycopeptidase (almond) digestion. 3567160 3 44 theme pyridylamino 465:476 arg1 derivatives 478:488 pyridylamino derivatives 465:488 pyridylamino derivatives of the oligosaccharides 465:512 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 6 45 dep see 986:988 arg1 formula 977:983 formula 977:983 formula 977:983 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 5 46 used used 778:781 arg2 spectroscopy 761:772 High-resolution proton nuclear magnetic resonance spectroscopy 711:772 High-resolution proton nuclear magnetic resonance spectroscopy 711:772 High-resolution proton nuclear magnetic resonance spectroscopy was used along with chemical methods to determine the structures of the separated oligosaccharides. 3567160 4 47 dep kinds 630:634 arg1 out 616:618 out 616:618 out 616:618 It was possible to separate 15 out of the 16 kinds of oligosaccharides that have been suggested to exist in normal human IgG. 3567160 6 48 attach predominant 999:1009 arg2 oligosaccharide 938:952 a biantennary complex-type oligosaccharide 911:952 a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) 911:994 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 6 48 attach predominant 999:1009 arg1 IgG 907:909 normal IgG 900:909 normal IgG 900:909 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 6 48 attach predominant 999:1009 arg2 predominant 999:1009 predominant 999:1009 predominant 999:1009 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 5 49 theme oligosaccharides 856:871 arg1 structures 828:837 the structures 824:837 the structures of the separated oligosaccharides 824:871 High-resolution proton nuclear magnetic resonance spectroscopy was used along with chemical methods to determine the structures of the separated oligosaccharides. 3567160 7 50 theme myeloma 1250:1256 arg1 proteins 1262:1269 three myeloma IgG proteins 1244:1269 three myeloma IgG proteins 1244:1269 The results obtained for normal IgG were compared with those obtained for three myeloma IgG proteins. 3567160 5 51 theme proton 727:732 arg1 resonance 751:759 High-resolution proton nuclear magnetic resonance 711:759 High-resolution proton nuclear magnetic resonance spectroscopy 711:772 High-resolution proton nuclear magnetic resonance spectroscopy was used along with chemical methods to determine the structures of the separated oligosaccharides. 3567160 10 52 theme particular 1591:1600 arg1 interest 1602:1609 particular interest 1591:1609 particular interest 1591:1609 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 3 53 with aminated 392:399 arg1 reagent 420:426 a fluorescent reagent 406:426 a fluorescent reagent 406:426 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 3 53 with aminated 392:399 arg1 2-aminopyridine 429:443 2-aminopyridine 429:443 2-aminopyridine 429:443 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 6 54 from predominant 999:1009 arg1 IgG 907:909 normal IgG 900:909 normal IgG 900:909 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 3 55 theme reverse-phase 531:543 arg1 chromatography 569:582 reverse-phase high-performance liquid chromatography 531:582 reverse-phase high-performance liquid chromatography 531:582 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 0 56 theme oligosaccharides 45:60 arg1 study 23:27 Comparative structural study 0:27 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G 0:110 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. 3567160 5 57 theme nuclear 734:740 arg1 resonance 751:759 High-resolution proton nuclear magnetic resonance 711:759 High-resolution proton nuclear magnetic resonance spectroscopy 711:772 High-resolution proton nuclear magnetic resonance spectroscopy was used along with chemical methods to determine the structures of the separated oligosaccharides. 3567160 2 58 theme Asparagine-linked 212:228 arg1 oligosaccharides 238:253 Asparagine-linked neutral oligosaccharides 212:253 Asparagine-linked neutral oligosaccharides 212:253 Asparagine-linked neutral oligosaccharides were released by N-oligosaccharide glycopeptidase (almond) digestion. 3567160 2 59 theme neutral 230:236 arg1 oligosaccharides 238:253 Asparagine-linked neutral oligosaccharides 212:253 Asparagine-linked neutral oligosaccharides 212:253 Asparagine-linked neutral oligosaccharides were released by N-oligosaccharide glycopeptidase (almond) digestion. 3567160 7 60 theme IgG 1258:1260 arg1 proteins 1262:1269 three myeloma IgG proteins 1244:1269 three myeloma IgG proteins 1244:1269 The results obtained for normal IgG were compared with those obtained for three myeloma IgG proteins. 3567160 3 61 theme high-performance 545:560 arg1 chromatography 569:582 reverse-phase high-performance liquid chromatography 531:582 reverse-phase high-performance liquid chromatography 531:582 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 5 62 theme magnetic 742:749 arg1 resonance 751:759 High-resolution proton nuclear magnetic resonance 711:759 High-resolution proton nuclear magnetic resonance spectroscopy 711:772 High-resolution proton nuclear magnetic resonance spectroscopy was used along with chemical methods to determine the structures of the separated oligosaccharides. 3567160 6 63 theme normal 900:905 arg1 IgG 907:909 normal IgG 900:909 normal IgG 900:909 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 6 64 with biantennary 1057:1067 arg1 N-acetylglucosamine 1084:1102 bisecting N-acetylglucosamine 1074:1102 bisecting N-acetylglucosamine 1074:1102 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 1 65 theme oligosaccharides 131:146 arg1 structures 117:126 The structures 113:126 The structures of oligosaccharides of normal and pathological immunoglobulin G (IgG) 113:196 The structures of oligosaccharides of normal and pathological immunoglobulin G (IgG) are reported. 3567160 3 66 theme reducing 329:336 arg1 aminated 392:399 aminated 392:399 aminated 392:399 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 3 66 theme reducing 329:336 arg1 ends 338:341 The reducing ends 325:341 The reducing ends of the oligosaccharide chains thus obtained 325:385 The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. 3567160 2 67 theme glycopeptidase 290:303 arg1 digestion 314:322 N-oligosaccharide glycopeptidase (almond) digestion 272:322 N-oligosaccharide glycopeptidase (almond) digestion 272:322 Asparagine-linked neutral oligosaccharides were released by N-oligosaccharide glycopeptidase (almond) digestion. 3567160 9 68 theme disease 1561:1567 arg1 protein 1569:1575 the heavy-chain disease protein 1545:1575 the heavy-chain disease protein Per 1545:1579 We show that the fractions of fucose-containing oligosaccharides are markedly decreased in the heavy-chain disease protein Per. 3567160 8 69 theme present 1377:1383 arg1 work 1385:1388 the present work 1373:1388 the present work 1373:1388 It has been found that the most abundant species that exist in the pathological proteins analyzed in the present work lack one or two galactose residues at the nonreducing terminal. 3567160 6 70 theme bisecting 1074:1082 arg1 N-acetylglucosamine 1084:1102 bisecting N-acetylglucosamine 1074:1102 bisecting N-acetylglucosamine 1074:1102 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 0 71 theme normal 71:76 arg1 G 110:110 human normal and pathological immunoglobulin G 65:110 human normal and pathological immunoglobulin G 65:110 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. 3567160 2 72 theme N-oligosaccharide 272:288 arg1 almond 306:311 almond 306:311 almond 306:311 Asparagine-linked neutral oligosaccharides were released by N-oligosaccharide glycopeptidase (almond) digestion. 3567160 2 72 theme N-oligosaccharide 272:288 arg1 glycopeptidase 290:303 N-oligosaccharide glycopeptidase 272:303 N-oligosaccharide glycopeptidase (almond) digestion 272:322 Asparagine-linked neutral oligosaccharides were released by N-oligosaccharide glycopeptidase (almond) digestion. 3567160 8 73 theme abundant 1304:1311 arg1 species 1313:1319 the most abundant species 1295:1319 the most abundant species that exist in the pathological proteins analyzed in the present work 1295:1388 It has been found that the most abundant species that exist in the pathological proteins analyzed in the present work lack one or two galactose residues at the nonreducing terminal. 3567160 1 74 theme normal 151:156 arg1 IgG 193:195 IgG 193:195 IgG 193:195 The structures of oligosaccharides of normal and pathological immunoglobulin G (IgG) are reported. 3567160 1 74 theme normal 151:156 arg1 G 190:190 immunoglobulin G 175:190 normal and pathological immunoglobulin G (IgG) 151:196 The structures of oligosaccharides of normal and pathological immunoglobulin G (IgG) are reported. 3567160 4 75 theme human 700:704 arg1 IgG 706:708 normal human IgG 693:708 normal human IgG 693:708 It was possible to separate 15 out of the 16 kinds of oligosaccharides that have been suggested to exist in normal human IgG. 3567160 6 76 dep residue 968:974 arg1 see 986:988 see 986:988 see text 986:993 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 0 77 theme human 65:69 arg1 G 110:110 human normal and pathological immunoglobulin G 65:110 human normal and pathological immunoglobulin G 65:110 Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. 3567160 5 78 theme separated 846:854 arg1 oligosaccharides 856:871 the separated oligosaccharides 842:871 the separated oligosaccharides 842:871 High-resolution proton nuclear magnetic resonance spectroscopy was used along with chemical methods to determine the structures of the separated oligosaccharides. 3567160 6 79 theme small 1154:1158 arg1 quantity 1160:1167 a very small quantity 1147:1167 a very small quantity 1147:1167 It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. 3567160 10 80 theme complex-type 1673:1684 arg1 component 1646:1654 the major component 1636:1654 the major component 1636:1654 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 10 80 theme complex-type 1673:1684 arg1 oligosaccharide 1686:1700 a biantennary complex-type oligosaccharide 1659:1700 a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components 1659:1836 It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components. 3567160 5 81 theme chemical 794:801 arg1 methods 803:809 chemical methods 794:809 chemical methods 794:809 High-resolution proton nuclear magnetic resonance spectroscopy was used along with chemical methods to determine the structures of the separated oligosaccharides. 8870235 0 0 theme pH 71:72 arg1 chromatography 89:102 high pH anion-exchange chromatography 66:102 high pH anion-exchange chromatography 66:102 The resolution of the neutral N-linked oligosaccharides of IgG by high pH anion-exchange chromatography. 8870235 7 1 theme enzyme 1336:1341 arg1 F 1365:1365 the enzyme peptide-N-glycosidase F 1332:1365 the enzyme peptide-N-glycosidase F 1332:1365 The technique was applied to the identification of neutral N-linked oligosaccharides released from human immunoglobulin G using the enzyme peptide-N-glycosidase F. 8870235 2 2 theme quantities 374:383 arg1 detection 352:360 the detection 348:360 the detection of picomole quantities of heterogeneous mixtures of oligosaccharide 348:428 When coupled with pulsed amperometric detection, the technique permits the detection of picomole quantities of heterogeneous mixtures of oligosaccharide without the need for derivatisation. 8870235 1 3 theme derived 251:257 arg1 oligosaccharides 259:274 glycoprotein derived oligosaccharides 238:274 glycoprotein derived oligosaccharides 238:274 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 0 4 theme high 66:69 arg1 chromatography 89:102 high pH anion-exchange chromatography 66:102 high pH anion-exchange chromatography 66:102 The resolution of the neutral N-linked oligosaccharides of IgG by high pH anion-exchange chromatography. 8870235 4 5 theme sialylated 910:919 arg1 structures 921:930 sialylated structures 910:930 sialylated structures 910:930 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 4 6 from influence 821:829 arg1 position 873:880 elution position 865:880 elution position 865:880 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 2 7 theme picomole 365:372 arg1 quantities 374:383 picomole quantities 365:383 picomole quantities of heterogeneous mixtures of oligosaccharide 365:428 When coupled with pulsed amperometric detection, the technique permits the detection of picomole quantities of heterogeneous mixtures of oligosaccharide without the need for derivatisation. 8870235 1 8 theme oligosaccharides 259:274 arg1 analysis 226:233 the qualitative analysis 210:233 the qualitative analysis of glycoprotein derived oligosaccharides 210:274 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 1 9 link derived 251:257 arg1 oligosaccharides 259:274 glycoprotein derived oligosaccharides 238:274 glycoprotein derived oligosaccharides 238:274 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 2 10 theme amperometric 302:313 arg1 detection 315:323 pulsed amperometric detection 295:323 pulsed amperometric detection 295:323 When coupled with pulsed amperometric detection, the technique permits the detection of picomole quantities of heterogeneous mixtures of oligosaccharide without the need for derivatisation. 8870235 4 11 link N-linked 781:788 arg1 oligosaccharides 790:805 seven commercially available neutral N-linked oligosaccharides 744:805 seven commercially available neutral N-linked oligosaccharides 744:805 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 0 12 theme anion-exchange 74:87 arg1 chromatography 89:102 high pH anion-exchange chromatography 66:102 high pH anion-exchange chromatography 66:102 The resolution of the neutral N-linked oligosaccharides of IgG by high pH anion-exchange chromatography. 8870235 1 13 gly glycoprotein 238:249 arg1 glycoprotein 238:249 glycoprotein 238:249 glycoprotein 238:249 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 2 14 theme pulsed 295:300 arg1 detection 315:323 pulsed amperometric detection 295:323 pulsed amperometric detection 295:323 When coupled with pulsed amperometric detection, the technique permits the detection of picomole quantities of heterogeneous mixtures of oligosaccharide without the need for derivatisation. 8870235 5 15 theme sequential 1000:1009 arg1 digestion 1011:1019 sequential digestion 1000:1019 sequential digestion with specific exoglycosidases 1000:1049 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 7 16 theme immunoglobulin 1309:1322 arg1 G 1324:1324 human immunoglobulin G 1303:1324 human immunoglobulin G 1303:1324 The technique was applied to the identification of neutral N-linked oligosaccharides released from human immunoglobulin G using the enzyme peptide-N-glycosidase F. 8870235 3 17 gly sialylated 540:549 arg1 oligosaccharides 551:566 sialylated oligosaccharides 540:566 sialylated oligosaccharides 540:566 The applications of HPAEC have generally been limited to the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems. 8870235 4 18 gly sialylated 910:919 arg1 structures 921:930 sialylated structures 910:930 sialylated structures 910:930 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 7 19 theme neutral 1255:1261 arg1 oligosaccharides 1272:1287 neutral N-linked oligosaccharides 1255:1287 neutral N-linked oligosaccharides released from human immunoglobulin G 1255:1324 The technique was applied to the identification of neutral N-linked oligosaccharides released from human immunoglobulin G using the enzyme peptide-N-glycosidase F. 8870235 5 20 theme N-linked 959:966 arg1 oligosaccharide 968:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 2 21 theme oligosaccharide 414:428 arg1 mixtures 402:409 heterogeneous mixtures 388:409 heterogeneous mixtures of oligosaccharide 388:428 When coupled with pulsed amperometric detection, the technique permits the detection of picomole quantities of heterogeneous mixtures of oligosaccharide without the need for derivatisation. 8870235 7 22 theme peptide-N-glycosidase 1343:1363 arg1 F 1365:1365 the enzyme peptide-N-glycosidase F 1332:1365 the enzyme peptide-N-glycosidase F 1332:1365 The technique was applied to the identification of neutral N-linked oligosaccharides released from human immunoglobulin G using the enzyme peptide-N-glycosidase F. 8870235 4 23 theme neutral 773:779 arg1 oligosaccharides 790:805 seven commercially available neutral N-linked oligosaccharides 744:805 seven commercially available neutral N-linked oligosaccharides 744:805 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 3 24 theme oligosaccharides 551:566 arg1 analysis 528:535 the analysis 524:535 the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems 524:680 The applications of HPAEC have generally been limited to the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems. 8870235 7 25 theme human 1303:1307 arg1 G 1324:1324 human immunoglobulin G 1303:1324 human immunoglobulin G 1303:1324 The technique was applied to the identification of neutral N-linked oligosaccharides released from human immunoglobulin G using the enzyme peptide-N-glycosidase F. 8870235 0 26 link N-linked 30:37 arg1 oligosaccharides 39:54 the neutral N-linked oligosaccharides 18:54 the neutral N-linked oligosaccharides of IgG 18:61 The resolution of the neutral N-linked oligosaccharides of IgG by high pH anion-exchange chromatography. 8870235 4 27 theme available 763:771 arg1 oligosaccharides 790:805 seven commercially available neutral N-linked oligosaccharides 744:805 seven commercially available neutral N-linked oligosaccharides 744:805 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 2 28 theme mixtures 402:409 arg1 quantities 374:383 picomole quantities 365:383 picomole quantities of heterogeneous mixtures of oligosaccharide 365:428 When coupled with pulsed amperometric detection, the technique permits the detection of picomole quantities of heterogeneous mixtures of oligosaccharide without the need for derivatisation. 8870235 5 29 with digestion 1011:1019 arg1 exoglycosidases 1035:1049 specific exoglycosidases 1026:1049 specific exoglycosidases 1026:1049 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 7 30 attach released 1289:1296 arg2 oligosaccharides 1272:1287 neutral N-linked oligosaccharides 1255:1287 neutral N-linked oligosaccharides released from human immunoglobulin G 1255:1324 The technique was applied to the identification of neutral N-linked oligosaccharides released from human immunoglobulin G using the enzyme peptide-N-glycosidase F. 8870235 7 30 attach released 1289:1296 arg1 G 1324:1324 human immunoglobulin G 1303:1324 human immunoglobulin G 1303:1324 The technique was applied to the identification of neutral N-linked oligosaccharides released from human immunoglobulin G using the enzyme peptide-N-glycosidase F. 8870235 5 31 link N-linked 959:966 arg1 oligosaccharide 968:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 3 32 dep oligosaccharides 551:566 arg1 possible 588:595 possible 588:595 possible 588:595 The applications of HPAEC have generally been limited to the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems. 8870235 1 33 theme major 189:193 arg1 development 195:205 a major development 187:205 a major development 187:205 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 5 34 theme specific 1026:1033 arg1 exoglycosidases 1035:1049 specific exoglycosidases 1026:1049 specific exoglycosidases 1026:1049 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 3 35 theme sialylated 540:549 arg1 oligosaccharides 551:566 sialylated oligosaccharides 540:566 sialylated oligosaccharides 540:566 The applications of HPAEC have generally been limited to the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems. 8870235 2 36 theme heterogeneous 388:400 arg1 mixtures 402:409 heterogeneous mixtures 388:409 heterogeneous mixtures of oligosaccharide 388:428 When coupled with pulsed amperometric detection, the technique permits the detection of picomole quantities of heterogeneous mixtures of oligosaccharide without the need for derivatisation. 8870235 0 37 theme N-linked 30:37 arg1 oligosaccharides 39:54 the neutral N-linked oligosaccharides 18:54 the neutral N-linked oligosaccharides of IgG 18:61 The resolution of the neutral N-linked oligosaccharides of IgG by high pH anion-exchange chromatography. 8870235 6 38 theme standard 1152:1159 arg1 position 1171:1178 This standard's elution position 1147:1178 This standard's elution position 1147:1178 This standard's elution position was confirmed by HPAEC. 8870235 3 39 theme HPAEC 487:491 arg1 applications 471:482 The applications 467:482 The applications of HPAEC 467:491 The applications of HPAEC have generally been limited to the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems. 8870235 0 40 theme neutral 22:28 arg1 oligosaccharides 39:54 the neutral N-linked oligosaccharides 18:54 the neutral N-linked oligosaccharides of IgG 18:61 The resolution of the neutral N-linked oligosaccharides of IgG by high pH anion-exchange chromatography. 8870235 7 41 theme N-linked 1263:1270 arg1 oligosaccharides 1272:1287 neutral N-linked oligosaccharides 1255:1287 neutral N-linked oligosaccharides released from human immunoglobulin G 1255:1324 The technique was applied to the identification of neutral N-linked oligosaccharides released from human immunoglobulin G using the enzyme peptide-N-glycosidase F. 8870235 3 42 theme neutral 633:639 arg1 oligosaccharides 641:656 neutral oligosaccharides 633:656 neutral oligosaccharides with the latest systems 633:680 The applications of HPAEC have generally been limited to the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems. 8870235 5 43 theme standard 935:942 arg1 oligosaccharide 968:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 5 44 gly monosialylated 944:957 arg1 oligosaccharide 968:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 3 45 theme heterogenous 608:619 arg1 mixtures 621:628 heterogenous mixtures 608:628 heterogenous mixtures of neutral oligosaccharides with the latest systems 608:680 The applications of HPAEC have generally been limited to the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems. 8870235 0 46 theme oligosaccharides 39:54 arg1 resolution 4:13 The resolution 0:13 The resolution of the neutral N-linked oligosaccharides of IgG by high pH anion-exchange chromatography 0:102 The resolution of the neutral N-linked oligosaccharides of IgG by high pH anion-exchange chromatography. 8870235 7 47 link N-linked 1263:1270 arg1 oligosaccharides 1272:1287 neutral N-linked oligosaccharides 1255:1287 neutral N-linked oligosaccharides released from human immunoglobulin G 1255:1324 The technique was applied to the identification of neutral N-linked oligosaccharides released from human immunoglobulin G using the enzyme peptide-N-glycosidase F. 8870235 4 48 used used 691:694 arg2 We 683:684 We 683:684 We 683:684 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 5 49 dep monogalactosylated 1064:1081 arg1 diantennary 1084:1094 diantennary 1084:1094 diantennary 1084:1094 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 7 50 theme oligosaccharides 1272:1287 arg1 identification 1237:1250 the identification 1233:1250 the identification of neutral N-linked oligosaccharides released from human immunoglobulin G 1233:1324 The technique was applied to the identification of neutral N-linked oligosaccharides released from human immunoglobulin G using the enzyme peptide-N-glycosidase F. 8870235 4 51 theme monosaccharide 834:847 arg1 substitution 849:860 monosaccharide substitution 834:860 monosaccharide substitution 834:860 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 4 52 theme elution 865:871 arg1 position 873:880 elution position 865:880 elution position 865:880 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 1 53 theme high 125:128 arg1 chromatography 148:161 high pH anion-exchange chromatography 125:161 high pH anion-exchange chromatography (HPAEC) 125:169 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 1 53 theme high 125:128 arg1 HPAEC 164:168 HPAEC 164:168 HPAEC 164:168 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 4 54 theme oligosaccharides 790:805 arg1 panel 735:739 a panel 733:739 a panel of seven commercially available neutral N-linked oligosaccharides 733:805 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 1 55 theme qualitative 214:224 arg1 analysis 226:233 the qualitative analysis 210:233 the qualitative analysis of glycoprotein derived oligosaccharides 210:274 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 5 56 theme monogalactosylated 1064:1081 arg1 oligosaccharide 1096:1110 a monogalactosylated, diantennary oligosaccharide 1062:1110 a monogalactosylated, diantennary oligosaccharide which is commercially unavailable 1062:1144 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 5 56 theme monogalactosylated 1064:1081 arg1 unavailable 1134:1144 unavailable 1134:1144 unavailable 1134:1144 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 1 57 dep derived 251:257 arg1 glycoprotein 238:249 glycoprotein 238:249 glycoprotein 238:249 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 3 58 theme latest 667:672 arg1 systems 674:680 the latest systems 663:680 the latest systems 663:680 The applications of HPAEC have generally been limited to the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems. 8870235 4 59 theme N-linked 781:788 arg1 oligosaccharides 790:805 seven commercially available neutral N-linked oligosaccharides 744:805 seven commercially available neutral N-linked oligosaccharides 744:805 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 1 60 theme pH 130:131 arg1 chromatography 148:161 high pH anion-exchange chromatography 125:161 high pH anion-exchange chromatography (HPAEC) 125:169 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 1 60 theme pH 130:131 arg1 HPAEC 164:168 HPAEC 164:168 HPAEC 164:168 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 5 61 mod modified 988:995 arg3 digestion 1011:1019 sequential digestion 1000:1019 sequential digestion with specific exoglycosidases 1000:1049 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 5 61 mod modified 988:995 arg1 oligosaccharide 968:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 3 62 with oligosaccharides 641:656 arg1 systems 674:680 the latest systems 663:680 the latest systems 663:680 The applications of HPAEC have generally been limited to the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems. 8870235 5 63 theme monosialylated 944:957 arg1 oligosaccharide 968:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide 933:982 A standard monosialylated N-linked oligosaccharide was modified by sequential digestion with specific exoglycosidases to produce a monogalactosylated, diantennary oligosaccharide which is commercially unavailable. 8870235 3 64 theme oligosaccharides 641:656 arg1 mixtures 621:628 heterogenous mixtures 608:628 heterogenous mixtures of neutral oligosaccharides with the latest systems 608:680 The applications of HPAEC have generally been limited to the analysis of sialylated oligosaccharides, however, it is now possible to analyse heterogenous mixtures of neutral oligosaccharides with the latest systems. 8870235 6 65 theme elution 1163:1169 arg1 position 1171:1178 This standard's elution position 1147:1178 This standard's elution position 1147:1178 This standard's elution position was confirmed by HPAEC. 8870235 1 66 theme anion-exchange 133:146 arg1 chromatography 148:161 high pH anion-exchange chromatography 125:161 high pH anion-exchange chromatography (HPAEC) 125:169 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 1 66 theme anion-exchange 133:146 arg1 HPAEC 164:168 HPAEC 164:168 HPAEC 164:168 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 8870235 0 67 theme IgG 59:61 arg1 oligosaccharides 39:54 the neutral N-linked oligosaccharides 18:54 the neutral N-linked oligosaccharides of IgG 18:61 The resolution of the neutral N-linked oligosaccharides of IgG by high pH anion-exchange chromatography. 8870235 4 68 theme substitution 849:860 arg1 influence 821:829 the influence 817:829 the influence of monosaccharide substitution on elution position 817:880 We have used such a system to separate completely a panel of seven commercially available neutral N-linked oligosaccharides and found the influence of monosaccharide substitution on elution position to be identical to that for sialylated structures. 8870235 1 69 theme chromatography 148:161 arg1 introduction 109:120 The introduction 105:120 The introduction of high pH anion-exchange chromatography (HPAEC) 105:169 The introduction of high pH anion-exchange chromatography (HPAEC) has represented a major development in the qualitative analysis of glycoprotein derived oligosaccharides. 12652077 2 0 theme liquid 538:543 arg1 chromatography 545:558 reversed-phase high-performance liquid chromatography 506:558 reversed-phase high-performance liquid chromatography 506:558 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 1 1 with complicated 183:193 arg1 RA 222:223 RA 222:223 RA 222:223 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 12652077 1 1 with complicated 183:193 arg1 arthritis 211:219 rheumatoid arthritis 200:219 rheumatoid arthritis (RA) 200:224 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 12652077 2 2 from individuals 474:484 arg1 IgG 401:403 IgG 401:403 IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals 401:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 2 from individuals 474:484 arg1 oligosaccharides 381:396 N-linked oligosaccharides 372:396 N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals 372:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 3 theme reversed-phase 506:519 arg1 chromatography 545:558 reversed-phase high-performance liquid chromatography 506:558 reversed-phase high-performance liquid chromatography 506:558 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 5 4 theme healthy 1414:1420 arg1 individuals 1422:1432 healthy individuals 1414:1432 healthy individuals 1414:1432 The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. 12652077 6 5 theme SS 1505:1506 arg1 patients 1508:1515 primary SS patients 1497:1515 primary SS patients with a high incidence of RF 1497:1543 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 7 6 theme future 1729:1734 arg1 complication 1736:1747 future complication 1729:1747 future complication with RA 1729:1755 These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA. 12652077 5 7 theme similar 1394:1400 arg1 levels 1387:1392 levels 1387:1392 levels similar to those of healthy individuals 1387:1432 The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. 12652077 7 8 contain carrying 1653:1660 arg2 oligosaccharides 1680:1695 abnormal N-linked oligosaccharides 1662:1695 abnormal N-linked oligosaccharides 1662:1695 These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA. 12652077 7 8 contain carrying 1653:1660 arg1 IgG 1649:1651 IgG 1649:1651 IgG carrying abnormal N-linked oligosaccharides in primary SS 1649:1709 These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA. 12652077 3 9 theme IgG 710:712 arg1 samples 714:720 the IgG samples 706:720 the IgG samples obtained from primary SS patients, RA patients, and healthy individuals 706:792 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 2 10 with combination 564:574 arg1 treatment 607:615 sequential exoglycosidase treatment 581:615 sequential exoglycosidase treatment 581:615 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 10 with combination 564:574 arg1 spectrometry 685:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 6 11 with patients 1508:1515 arg1 incidence 1529:1537 a high incidence 1522:1537 a high incidence of RF 1522:1543 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 7 12 link N-linked 1671:1678 arg1 oligosaccharides 1680:1695 abnormal N-linked oligosaccharides 1662:1695 abnormal N-linked oligosaccharides 1662:1695 These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA. 12652077 2 13 from patients 424:431 arg1 IgG 401:403 IgG 401:403 IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals 401:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 13 from patients 424:431 arg1 oligosaccharides 381:396 N-linked oligosaccharides 372:396 N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals 372:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 14 theme mass 680:683 arg1 spectrometry 685:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 3 15 theme primary 736:742 arg1 patients 747:754 primary SS patients 736:754 primary SS patients 736:754 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 2 16 theme ionization 654:663 arg1 spectrometry 685:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 3 17 theme same 808:811 arg1 series 813:818 the same series 804:818 the same series of biantennary complex-type oligosaccharides 804:863 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 4 18 theme primary 1125:1131 arg1 patients 1136:1143 primary SS patients 1125:1143 primary SS patients 1125:1143 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 5 19 theme IgG 1271:1273 arg1 oligosaccharides 1275:1290 IgG oligosaccharides 1271:1290 IgG oligosaccharides 1271:1290 The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. 12652077 3 20 theme RA 757:758 arg1 patients 760:767 RA patients 757:767 RA patients 757:767 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 0 21 theme primary 60:66 arg1 syndrome 78:85 primary Sjögren's syndrome 60:85 primary Sjögren's syndrome 60:85 Structural studies on IgG oligosaccharides of patients with primary Sjögren's syndrome. 12652077 1 22 theme abnormal 258:265 arg1 oligosaccharides 276:291 abnormal N-linked oligosaccharides 258:291 abnormal N-linked oligosaccharides 258:291 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 12652077 6 23 theme high 1524:1527 arg1 incidence 1529:1537 a high incidence 1522:1537 a high incidence of RF 1522:1543 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 1 24 theme autoimmune 118:127 arg1 disease 129:135 an autoimmune disease 115:135 an autoimmune disease 115:135 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 12652077 1 24 theme autoimmune 118:127 arg1 syndrome 98:105 Sjögren's syndrome 88:105 Sjögren's syndrome (SS) 88:110 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 12652077 7 25 theme N-linked 1671:1678 arg1 oligosaccharides 1680:1695 abnormal N-linked oligosaccharides 1662:1695 abnormal N-linked oligosaccharides 1662:1695 These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA. 12652077 2 26 theme SS 421:422 arg1 patients 424:431 12 primary SS patients 410:431 12 primary SS patients without RA 410:442 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 4 27 theme patients 1136:1143 arg1 IgG 1118:1120 the serum IgG 1108:1120 the serum IgG of primary SS patients 1108:1143 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 3 28 theme complex-type 835:846 arg1 oligosaccharides 848:863 biantennary complex-type oligosaccharides 823:863 biantennary complex-type oligosaccharides 823:863 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 2 29 theme RA 447:448 arg1 patients 450:457 9 RA patients 445:457 9 RA patients 445:457 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 30 theme exoglycosidase 592:605 arg1 treatment 607:615 sequential exoglycosidase treatment 581:615 sequential exoglycosidase treatment 581:615 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 31 dep order 297:301 arg1 investigate 306:316 investigate 306:316 to investigate the relationship between SS and RA 303:351 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 3 32 theme healthy 774:780 arg1 individuals 782:792 healthy individuals 774:792 healthy individuals 774:792 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 2 33 link N-linked 372:379 arg1 oligosaccharides 381:396 N-linked oligosaccharides 372:396 N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals 372:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 5 34 theme galactosylation 1312:1326 arg1 levels 1328:1333 galactosylation levels 1312:1333 galactosylation levels as low as those of RA patients 1312:1364 The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. 12652077 2 35 theme oligosaccharides 381:396 arg1 structures 358:367 the structures 354:367 the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals 354:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 36 theme laser 637:641 arg1 spectrometry 685:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 0 37 theme Structural 0:9 arg1 studies 11:17 Structural studies 0:17 Structural studies on IgG oligosaccharides of patients with primary Sjögren's syndrome 0:85 Structural studies on IgG oligosaccharides of patients with primary Sjögren's syndrome. 12652077 6 38 theme galactosylation 1565:1579 arg1 group 1581:1585 the low galactosylation group 1557:1585 the low galactosylation group 1557:1585 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 6 39 dep did 1591:1593 arg1 as 1588:1589 as 1588:1589 as 1588:1589 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 4 40 theme patients 1024:1031 arg1 IgG 1014:1016 the IgG 1010:1016 the IgG of RA patients 1010:1031 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 4 41 link N-linked 970:977 arg1 oligosaccharides 979:994 galactose-lacking N-linked oligosaccharides 952:994 galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients 952:1031 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 3 42 theme oligosaccharide 888:902 arg1 ratio 874:878 the ratio 870:878 the ratio of each oligosaccharide 870:902 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 1 43 link N-linked 267:274 arg1 oligosaccharides 276:291 abnormal N-linked oligosaccharides 258:291 abnormal N-linked oligosaccharides 258:291 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 12652077 2 44 theme IgG 401:403 arg1 oligosaccharides 381:396 N-linked oligosaccharides 372:396 N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals 372:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 0 45 theme patients 46:53 arg1 oligosaccharides 26:41 IgG oligosaccharides 22:41 IgG oligosaccharides of patients with primary Sjögren's syndrome 22:85 Structural studies on IgG oligosaccharides of patients with primary Sjögren's syndrome. 12652077 6 46 theme factor 1471:1476 arg1 levels 1450:1455 levels 1450:1455 levels of rheumatoid factor (RF) 1450:1481 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 2 47 from patients 450:457 arg1 IgG 401:403 IgG 401:403 IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals 401:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 47 from patients 450:457 arg1 oligosaccharides 381:396 N-linked oligosaccharides 372:396 N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals 372:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 4 48 theme N-linked 970:977 arg1 oligosaccharides 979:994 galactose-lacking N-linked oligosaccharides 952:994 galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients 952:1031 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 2 49 theme high-performance 521:536 arg1 chromatography 545:558 reversed-phase high-performance liquid chromatography 506:558 reversed-phase high-performance liquid chromatography 506:558 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 5 50 theme primary 1189:1195 arg1 SS 1197:1198 primary SS 1189:1198 primary SS 1189:1198 The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. 12652077 4 51 theme serum 1112:1116 arg1 IgG 1118:1120 the serum IgG 1108:1120 the serum IgG of primary SS patients 1108:1143 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 4 52 theme galactose-lacking 952:968 arg1 oligosaccharides 979:994 galactose-lacking N-linked oligosaccharides 952:994 galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients 952:1031 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 1 53 contain carry 252:256 arg1 IgG 236:238 IgG 236:238 IgG 236:238 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 12652077 1 53 contain carry 252:256 arg2 oligosaccharides 276:291 abnormal N-linked oligosaccharides 258:291 abnormal N-linked oligosaccharides 258:291 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 12652077 6 54 theme primary 1497:1503 arg1 patients 1508:1515 primary SS patients 1497:1515 primary SS patients with a high incidence of RF 1497:1543 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 2 55 from oligosaccharides 381:396 arg1 patients 424:431 12 primary SS patients 410:431 12 primary SS patients without RA 410:442 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 55 from oligosaccharides 381:396 arg1 individuals 474:484 8 healthy individuals 464:484 8 healthy individuals 464:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 55 from oligosaccharides 381:396 arg1 patients 450:457 9 RA patients 445:457 9 RA patients 445:457 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 5 56 theme galactosylation 1245:1259 arg1 levels 1261:1266 the galactosylation levels 1241:1266 the galactosylation levels of IgG oligosaccharides 1241:1290 The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. 12652077 3 57 theme SS 744:745 arg1 patients 747:754 primary SS patients 736:754 primary SS patients 736:754 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 6 58 theme RF 1542:1543 arg1 incidence 1529:1537 a high incidence 1522:1537 a high incidence of RF 1522:1543 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 3 59 theme biantennary 823:833 arg1 oligosaccharides 848:863 biantennary complex-type oligosaccharides 823:863 biantennary complex-type oligosaccharides 823:863 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 2 60 theme healthy 466:472 arg1 individuals 474:484 8 healthy individuals 464:484 8 healthy individuals 464:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 4 61 theme SS 1133:1134 arg1 patients 1136:1143 primary SS patients 1125:1143 primary SS patients 1125:1143 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 7 62 theme abnormal 1662:1669 arg1 oligosaccharides 1680:1695 abnormal N-linked oligosaccharides 1662:1695 abnormal N-linked oligosaccharides 1662:1695 These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA. 12652077 7 63 theme primary 1700:1706 arg1 SS 1708:1709 primary SS 1700:1709 primary SS 1700:1709 These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA. 12652077 1 64 theme N-linked 267:274 arg1 oligosaccharides 276:291 abnormal N-linked oligosaccharides 258:291 abnormal N-linked oligosaccharides 258:291 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 12652077 2 65 theme primary 413:419 arg1 patients 424:431 12 primary SS patients 410:431 12 primary SS patients without RA 410:442 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 0 66 from studies 11:17 arg1 oligosaccharides 26:41 IgG oligosaccharides 22:41 IgG oligosaccharides of patients with primary Sjögren's syndrome 22:85 Structural studies on IgG oligosaccharides of patients with primary Sjögren's syndrome. 12652077 6 67 theme RA 1595:1596 arg1 patients 1598:1605 RA patients 1595:1605 RA patients 1595:1605 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 3 68 theme oligosaccharides 848:863 arg1 series 813:818 the same series 804:818 the same series of biantennary complex-type oligosaccharides 804:863 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 2 69 theme sequential 581:590 arg1 treatment 607:615 sequential exoglycosidase treatment 581:615 sequential exoglycosidase treatment 581:615 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 7 70 theme IgG 1649:1651 arg1 appearance 1635:1644 appearance 1635:1644 appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS 1635:1709 These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA. 12652077 2 71 theme desorption 643:652 arg1 spectrometry 685:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 72 theme N-linked 372:379 arg1 oligosaccharides 381:396 N-linked oligosaccharides 372:396 N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals 372:484 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 2 73 theme matrix-assisted 621:635 arg1 spectrometry 685:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 matrix-assisted laser desorption ionization time-of-flight mass spectrometry 621:696 In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 12652077 5 74 theme oligosaccharides 1275:1290 arg1 levels 1261:1266 the galactosylation levels 1241:1266 the galactosylation levels of IgG oligosaccharides 1241:1290 The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. 12652077 0 75 theme IgG 22:24 arg1 oligosaccharides 26:41 IgG oligosaccharides 22:41 IgG oligosaccharides of patients with primary Sjögren's syndrome 22:85 Structural studies on IgG oligosaccharides of patients with primary Sjögren's syndrome. 12652077 6 76 theme low 1561:1563 arg1 group 1581:1585 the low galactosylation group 1557:1585 the low galactosylation group 1557:1585 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 4 77 theme RA 1021:1022 arg1 patients 1024:1031 RA patients 1021:1031 RA patients 1021:1031 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 4 78 theme oligosaccharides 979:994 arg1 higher 1051:1056 higher 1051:1056 higher 1051:1056 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 4 78 theme oligosaccharides 979:994 arg1 incidence 939:947 The incidence 935:947 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients 935:1031 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 7 79 with complication 1736:1747 arg1 RA 1754:1755 RA 1754:1755 RA 1754:1755 These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA. 12652077 5 80 theme RA 1354:1355 arg1 patients 1357:1364 RA patients 1354:1364 RA patients 1354:1364 The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. 12652077 3 81 contain contained 794:802 arg1 All 699:701 All 699:701 All 699:701 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 3 81 contain contained 794:802 arg1 samples 714:720 the IgG samples 706:720 the IgG samples obtained from primary SS patients, RA patients, and healthy individuals 706:792 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 3 81 contain contained 794:802 arg2 series 813:818 the same series 804:818 the same series of biantennary complex-type oligosaccharides 804:863 All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. 12652077 5 82 with patients 1175:1182 arg1 SS 1197:1198 primary SS 1189:1198 primary SS 1189:1198 The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. 12652077 5 83 theme low 1338:1340 arg1 levels 1328:1333 galactosylation levels 1312:1333 galactosylation levels as low as those of RA patients 1312:1364 The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. 12652077 6 84 theme rheumatoid 1460:1469 arg1 RF 1479:1480 RF 1479:1480 RF 1479:1480 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 6 84 theme rheumatoid 1460:1469 arg1 factor 1471:1476 rheumatoid factor 1460:1476 rheumatoid factor (RF) 1460:1481 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 4 85 theme healthy 1073:1079 arg1 individuals 1081:1091 healthy individuals 1073:1091 healthy individuals 1073:1091 The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. 12652077 6 86 theme levels 1450:1455 arg1 Measurement 1435:1445 Measurement 1435:1445 Measurement of levels of rheumatoid factor (RF) 1435:1481 Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. 12652077 1 87 theme rheumatoid 200:209 arg1 RA 222:223 RA 222:223 RA 222:223 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 12652077 1 87 theme rheumatoid 200:209 arg1 arthritis 211:219 rheumatoid arthritis 200:219 rheumatoid arthritis (RA) 200:224 Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. 2138613 0 0 theme G 93:93 arg1 molecule 95:102 immunoglobulin G molecule 78:102 immunoglobulin G molecule 78:102 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 1 1 theme NMR 379:381 arg1 spectroscopy 383:394 1H NMR spectroscopy 376:394 1H NMR spectroscopy 376:394 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 1 2 theme sugar 193:197 arg1 chains 199:204 The heterogeneous asparagine-linked sugar chains 157:204 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G 157:242 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 1 3 theme reversed-phase 281:294 arg1 chromatography 320:333 reversed-phase high performance liquid chromatography 281:333 reversed-phase high performance liquid chromatography 281:333 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 0 4 theme immunoglobulin 78:91 arg1 molecule 95:102 immunoglobulin G molecule 78:102 immunoglobulin G molecule 78:102 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 0 5 from heterogeneity 11:23 arg1 Conformation 62:73 immunoglobulin G. Conformation 44:73 immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases 44:154 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 9 6 theme sugar 1491:1495 arg1 chains 1497:1502 its sugar chains 1487:1502 its sugar chains 1487:1502 Thus, protein conformation may influence the structure of its sugar chains. 2138613 3 7 theme IgG 567:569 arg1 chains 550:555 the non-bisected sugar chains 527:555 the non-bisected sugar chains of bovine IgG 527:569 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 1 8 theme high 296:299 arg1 chromatography 320:333 reversed-phase high performance liquid chromatography 281:333 reversed-phase high performance liquid chromatography 281:333 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 7 9 theme galactosyltransferases 1242:1263 arg1 specificities 1225:1237 the substrate specificities 1211:1237 the substrate specificities of galactosyltransferases 1211:1263 Such findings are in conflict with the substrate specificities of galactosyltransferases. 2138613 3 10 theme 1-6 728:730 arg1 branch 732:737 the Man alpha 1-6 branch 714:737 the Man alpha 1-6 branch 714:737 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 3 11 theme Man 595:597 arg1 branch 609:614 the Man alpha 1-3 branch 591:614 the Man alpha 1-3 branch 591:614 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 1 12 theme performance 301:311 arg1 chromatography 320:333 reversed-phase high performance liquid chromatography 281:333 reversed-phase high performance liquid chromatography 281:333 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 0 13 theme molecule 95:102 arg1 Conformation 62:73 immunoglobulin G. Conformation 44:73 immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases 44:154 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 3 14 theme alpha 722:726 arg1 branch 732:737 the Man alpha 1-6 branch 714:737 the Man alpha 1-6 branch 714:737 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 3 15 theme alpha 599:603 arg1 branch 609:614 the Man alpha 1-3 branch 591:614 the Man alpha 1-3 branch 591:614 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 8 16 theme of 1381:1382 arg1 branch 1402:1407 more of the Man alpha 1-3 branch 1376:1407 more of the Man alpha 1-3 branch 1376:1407 Whereas these enzymes derivatized more of the Man alpha 1-6 branch of native human IgG1, in denatured protein more of the Man alpha 1-3 branch was galactosylated. 2138613 2 17 theme immunoglobulin 402:415 arg1 sources 424:430 Both immunoglobulin (Ig) G sources 397:430 Both immunoglobulin (Ig) G sources 397:430 Both immunoglobulin (Ig) G sources contained eight non-bisected biantennary complexes and four bisected biantennary complexes. 2138613 1 18 theme liquid 313:318 arg1 chromatography 320:333 reversed-phase high performance liquid chromatography 281:333 reversed-phase high performance liquid chromatography 281:333 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 0 19 theme specificities 118:130 arg1 Conformation 62:73 immunoglobulin G. Conformation 44:73 immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases 44:154 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 2 20 theme biantennary 461:471 arg1 complexes 473:481 eight non-bisected biantennary complexes 442:481 eight non-bisected biantennary complexes 442:481 Both immunoglobulin (Ig) G sources contained eight non-bisected biantennary complexes and four bisected biantennary complexes. 2138613 8 21 theme alpha 1392:1396 arg1 branch 1402:1407 more of the Man alpha 1-3 branch 1376:1407 more of the Man alpha 1-3 branch 1376:1407 Whereas these enzymes derivatized more of the Man alpha 1-6 branch of native human IgG1, in denatured protein more of the Man alpha 1-3 branch was galactosylated. 2138613 8 22 theme Man 1312:1314 arg1 branch 1326:1331 the Man alpha 1-6 branch 1308:1331 the Man alpha 1-6 branch of native human IgG1 1308:1352 Whereas these enzymes derivatized more of the Man alpha 1-6 branch of native human IgG1, in denatured protein more of the Man alpha 1-3 branch was galactosylated. 2138613 4 23 theme N-acetylglucosaminyltransferase 859:889 arg1 specificities 803:815 the substrate specificities 789:815 the substrate specificities of the galactosyl-transferases and of the N-acetylglucosaminyltransferase III involved in their synthesis 789:921 This difference can be explained by the substrate specificities of the galactosyl-transferases and of the N-acetylglucosaminyltransferase III involved in their synthesis. 2138613 0 24 theme substrate 108:116 arg1 specificities 118:130 substrate specificities 108:130 substrate specificities of glycosyltransferases 108:154 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 7 25 theme Such 1176:1179 arg1 findings 1181:1188 Such findings 1176:1188 Such findings 1176:1188 Such findings are in conflict with the substrate specificities of galactosyltransferases. 2138613 2 26 theme bisected 492:499 arg1 complexes 513:521 four bisected biantennary complexes 487:521 four bisected biantennary complexes 487:521 Both immunoglobulin (Ig) G sources contained eight non-bisected biantennary complexes and four bisected biantennary complexes. 2138613 1 27 theme bovine 209:214 arg1 G 242:242 bovine and human immunoglobulins G 209:242 bovine and human immunoglobulins G 209:242 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 2 28 theme biantennary 501:511 arg1 complexes 513:521 four bisected biantennary complexes 487:521 four bisected biantennary complexes 487:521 Both immunoglobulin (Ig) G sources contained eight non-bisected biantennary complexes and four bisected biantennary complexes. 2138613 7 29 with conflict 1197:1204 arg1 specificities 1225:1237 the substrate specificities 1211:1237 the substrate specificities of galactosyltransferases 1211:1263 Such findings are in conflict with the substrate specificities of galactosyltransferases. 2138613 6 30 theme alpha 1123:1127 arg1 branch 1133:1138 the Man alpha 1-3 branch 1115:1138 the Man alpha 1-3 branch 1115:1138 The Man alpha 1-6 branch of all IgG1s was more highly galactosylated than the Man alpha 1-3 branch even in the non-bisected complexes. 2138613 5 31 theme residues 1000:1007 arg1 distribution 970:981 the distribution 966:981 the distribution of its galactose residues from bovine IgG and human IgG2 966:1038 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 2 32 theme G 422:422 arg1 sources 424:430 Both immunoglobulin (Ig) G sources 397:430 Both immunoglobulin (Ig) G sources 397:430 Both immunoglobulin (Ig) G sources contained eight non-bisected biantennary complexes and four bisected biantennary complexes. 2138613 0 33 theme Structural 0:9 arg1 heterogeneity 11:23 Structural heterogeneity 0:23 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 0:155 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 6 34 theme alpha 1049:1053 arg1 branch 1059:1064 The Man alpha 1-6 branch 1041:1064 The Man alpha 1-6 branch of all IgG1s 1041:1077 The Man alpha 1-6 branch of all IgG1s was more highly galactosylated than the Man alpha 1-3 branch even in the non-bisected complexes. 2138613 5 35 theme sugar 928:932 arg1 chains 934:939 The sugar chains 924:939 The sugar chains of human IgG1 924:953 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 8 36 theme alpha 1316:1320 arg1 branch 1326:1331 the Man alpha 1-6 branch 1308:1331 the Man alpha 1-6 branch of native human IgG1 1308:1352 Whereas these enzymes derivatized more of the Man alpha 1-6 branch of native human IgG1, in denatured protein more of the Man alpha 1-3 branch was galactosylated. 2138613 1 37 theme human 220:224 arg1 G 242:242 bovine and human immunoglobulins G 209:242 bovine and human immunoglobulins G 209:242 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 0 38 theme sugar 28:32 arg1 chains 34:39 sugar chains 28:39 sugar chains 28:39 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 5 39 from distribution 970:981 arg1 IgG 1021:1023 bovine IgG 1014:1023 bovine IgG 1014:1023 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 5 39 from distribution 970:981 arg1 IgG2 1035:1038 human IgG2 1029:1038 human IgG2 1029:1038 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 0 40 theme glycosyltransferases 135:154 arg1 molecule 95:102 immunoglobulin G molecule 78:102 immunoglobulin G molecule 78:102 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 0 40 theme glycosyltransferases 135:154 arg1 specificities 118:130 substrate specificities 108:130 substrate specificities of glycosyltransferases 108:154 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 5 41 theme galactose 990:998 arg1 residues 1000:1007 its galactose residues 986:1007 its galactose residues from bovine IgG and human IgG2 986:1038 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 5 42 theme bovine 1014:1019 arg1 IgG 1021:1023 bovine IgG 1014:1023 bovine IgG 1014:1023 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 1 43 theme immunoglobulins 226:240 arg1 G 242:242 bovine and human immunoglobulins G 209:242 bovine and human immunoglobulins G 209:242 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 3 44 theme bisected 676:683 arg1 complexes 685:693 the bisected complexes 672:693 the bisected complexes 672:693 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 3 45 theme branch 609:614 arg1 galactosylation 572:586 galactosylation 572:586 galactosylation of the Man alpha 1-3 branch 572:614 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 1 46 theme G 242:242 arg1 chains 199:204 The heterogeneous asparagine-linked sugar chains 157:204 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G 157:242 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 3 47 theme bovine 560:565 arg1 IgG 567:569 bovine IgG 560:569 bovine IgG 560:569 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 7 48 theme substrate 1215:1223 arg1 specificities 1225:1237 the substrate specificities 1211:1237 the substrate specificities of galactosyltransferases 1211:1263 Such findings are in conflict with the substrate specificities of galactosyltransferases. 2138613 8 49 theme denatured 1358:1366 arg1 protein 1368:1374 denatured protein 1358:1374 denatured protein 1358:1374 Whereas these enzymes derivatized more of the Man alpha 1-6 branch of native human IgG1, in denatured protein more of the Man alpha 1-3 branch was galactosylated. 2138613 5 50 theme human 944:948 arg1 IgG1 950:953 human IgG1 944:953 human IgG1 944:953 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 2 51 theme non-bisected 448:459 arg1 complexes 473:481 eight non-bisected biantennary complexes 442:481 eight non-bisected biantennary complexes 442:481 Both immunoglobulin (Ig) G sources contained eight non-bisected biantennary complexes and four bisected biantennary complexes. 2138613 0 52 theme chains 34:39 arg1 heterogeneity 11:23 Structural heterogeneity 0:23 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 0:155 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 1 53 link asparagine-linked 175:191 arg1 chains 199:204 The heterogeneous asparagine-linked sugar chains 157:204 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G 157:242 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 4 54 theme substrate 793:801 arg1 specificities 803:815 the substrate specificities 789:815 the substrate specificities of the galactosyl-transferases and of the N-acetylglucosaminyltransferase III involved in their synthesis 789:921 This difference can be explained by the substrate specificities of the galactosyl-transferases and of the N-acetylglucosaminyltransferase III involved in their synthesis. 2138613 0 55 gly heterogeneity 11:23 arg1 chains 34:39 sugar chains 28:39 sugar chains 28:39 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 8 56 theme IgG1 1349:1352 arg1 branch 1326:1331 the Man alpha 1-6 branch 1308:1331 the Man alpha 1-6 branch of native human IgG1 1308:1352 Whereas these enzymes derivatized more of the Man alpha 1-6 branch of native human IgG1, in denatured protein more of the Man alpha 1-3 branch was galactosylated. 2138613 0 57 theme G. 59:60 arg1 Conformation 62:73 immunoglobulin G. Conformation 44:73 immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases 44:154 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 5 58 theme IgG1 950:953 arg1 chains 934:939 The sugar chains 924:939 The sugar chains of human IgG1 924:953 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 2 59 contain contained 432:440 arg1 sources 424:430 Both immunoglobulin (Ig) G sources 397:430 Both immunoglobulin (Ig) G sources 397:430 Both immunoglobulin (Ig) G sources contained eight non-bisected biantennary complexes and four bisected biantennary complexes. 2138613 2 59 contain contained 432:440 arg2 complexes 473:481 eight non-bisected biantennary complexes 442:481 eight non-bisected biantennary complexes 442:481 Both immunoglobulin (Ig) G sources contained eight non-bisected biantennary complexes and four bisected biantennary complexes. 2138613 2 59 contain contained 432:440 arg2 complexes 513:521 four bisected biantennary complexes 487:521 four bisected biantennary complexes 487:521 Both immunoglobulin (Ig) G sources contained eight non-bisected biantennary complexes and four bisected biantennary complexes. 2138613 5 60 theme human 1029:1033 arg1 IgG2 1035:1038 human IgG2 1029:1038 human IgG2 1029:1038 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 8 61 theme human 1343:1347 arg1 IgG1 1349:1352 native human IgG1 1336:1352 native human IgG1 1336:1352 Whereas these enzymes derivatized more of the Man alpha 1-6 branch of native human IgG1, in denatured protein more of the Man alpha 1-3 branch was galactosylated. 2138613 0 62 theme immunoglobulin 44:57 arg1 Conformation 62:73 immunoglobulin G. Conformation 44:73 immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases 44:154 Structural heterogeneity of sugar chains in immunoglobulin G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. 2138613 3 63 theme branch 732:737 arg1 galactosylation 695:709 galactosylation 695:709 galactosylation of the Man alpha 1-6 branch 695:737 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 8 64 theme native 1336:1341 arg1 IgG1 1349:1352 native human IgG1 1336:1352 native human IgG1 1336:1352 Whereas these enzymes derivatized more of the Man alpha 1-6 branch of native human IgG1, in denatured protein more of the Man alpha 1-3 branch was galactosylated. 2138613 3 65 theme Man 718:720 arg1 branch 732:737 the Man alpha 1-6 branch 714:737 the Man alpha 1-6 branch 714:737 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 3 66 theme Man 646:648 arg1 1-6 656:658 the Man alpha 1-6 642:658 the Man alpha 1-6 642:658 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 3 67 theme non-bisected 531:542 arg1 chains 550:555 the non-bisected sugar chains 527:555 the non-bisected sugar chains of bovine IgG 527:569 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 5 68 from IgG 1021:1023 arg1 residues 1000:1007 its galactose residues 986:1007 its galactose residues from bovine IgG and human IgG2 986:1038 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 5 68 from IgG 1021:1023 arg1 distribution 970:981 the distribution 966:981 the distribution of its galactose residues from bovine IgG and human IgG2 966:1038 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 6 69 theme IgG1s 1073:1077 arg1 branch 1059:1064 The Man alpha 1-6 branch 1041:1064 The Man alpha 1-6 branch of all IgG1s 1041:1077 The Man alpha 1-6 branch of all IgG1s was more highly galactosylated than the Man alpha 1-3 branch even in the non-bisected complexes. 2138613 8 70 theme Man 1388:1390 arg1 branch 1402:1407 more of the Man alpha 1-3 branch 1376:1407 more of the Man alpha 1-3 branch 1376:1407 Whereas these enzymes derivatized more of the Man alpha 1-6 branch of native human IgG1, in denatured protein more of the Man alpha 1-3 branch was galactosylated. 2138613 4 71 theme galactosyl-transferases 824:846 arg1 specificities 803:815 the substrate specificities 789:815 the substrate specificities of the galactosyl-transferases and of the N-acetylglucosaminyltransferase III involved in their synthesis 789:921 This difference can be explained by the substrate specificities of the galactosyl-transferases and of the N-acetylglucosaminyltransferase III involved in their synthesis. 2138613 3 72 theme sugar 544:548 arg1 chains 550:555 the non-bisected sugar chains 527:555 the non-bisected sugar chains of bovine IgG 527:569 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 8 73 theme more 1376:1379 arg1 branch 1402:1407 more of the Man alpha 1-3 branch 1376:1407 more of the Man alpha 1-3 branch 1376:1407 Whereas these enzymes derivatized more of the Man alpha 1-6 branch of native human IgG1, in denatured protein more of the Man alpha 1-3 branch was galactosylated. 2138613 6 74 theme non-bisected 1152:1163 arg1 complexes 1165:1173 the non-bisected complexes 1148:1173 the non-bisected complexes 1148:1173 The Man alpha 1-6 branch of all IgG1s was more highly galactosylated than the Man alpha 1-3 branch even in the non-bisected complexes. 2138613 3 75 theme alpha 650:654 arg1 1-6 656:658 the Man alpha 1-6 642:658 the Man alpha 1-6 642:658 In the non-bisected sugar chains of bovine IgG, galactosylation of the Man alpha 1-3 branch predominated over that of the Man alpha 1-6, whereas in the bisected complexes galactosylation of the Man alpha 1-6 branch predominated. 2138613 9 76 theme chains 1497:1502 arg1 structure 1474:1482 the structure 1470:1482 the structure of its sugar chains 1470:1502 Thus, protein conformation may influence the structure of its sugar chains. 2138613 1 77 theme heterogeneous 161:173 arg1 chains 199:204 The heterogeneous asparagine-linked sugar chains 157:204 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G 157:242 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 6 78 theme Man 1119:1121 arg1 branch 1133:1138 the Man alpha 1-3 branch 1115:1138 the Man alpha 1-3 branch 1115:1138 The Man alpha 1-6 branch of all IgG1s was more highly galactosylated than the Man alpha 1-3 branch even in the non-bisected complexes. 2138613 6 79 theme Man 1045:1047 arg1 branch 1059:1064 The Man alpha 1-6 branch 1041:1064 The Man alpha 1-6 branch of all IgG1s 1041:1077 The Man alpha 1-6 branch of all IgG1s was more highly galactosylated than the Man alpha 1-3 branch even in the non-bisected complexes. 2138613 1 80 theme 1H 376:377 arg1 spectroscopy 383:394 1H NMR spectroscopy 376:394 1H NMR spectroscopy 376:394 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 1 81 theme asparagine-linked 175:191 arg1 chains 199:204 The heterogeneous asparagine-linked sugar chains 157:204 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G 157:242 The heterogeneous asparagine-linked sugar chains of bovine and human immunoglobulins G were separated into 12 components by reversed-phase high performance liquid chromatography, and their structures were determined by 1H NMR spectroscopy. 2138613 5 82 from IgG2 1035:1038 arg1 residues 1000:1007 its galactose residues 986:1007 its galactose residues from bovine IgG and human IgG2 986:1038 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 5 82 from IgG2 1035:1038 arg1 distribution 970:981 the distribution 966:981 the distribution of its galactose residues from bovine IgG and human IgG2 966:1038 The sugar chains of human IgG1 differs in the distribution of its galactose residues from bovine IgG and human IgG2. 2138613 9 83 theme protein 1435:1441 arg1 conformation 1443:1454 protein conformation 1435:1454 protein conformation 1435:1454 Thus, protein conformation may influence the structure of its sugar chains. 2813359 6 0 theme biantennary 1187:1197 arg1 oligosaccharides 1199:1214 biantennary oligosaccharides 1187:1214 biantennary oligosaccharides 1187:1214 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 6 1 theme positive 1095:1102 arg1 correlation 1104:1114 a positive correlation 1093:1114 a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides 1093:1214 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 3 2 theme standard 657:664 arg1 EPO 666:668 the standard EPO 653:668 the standard EPO 653:668 In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. 2813359 3 3 dep in 610:611 arg1 vitro 613:617 vitro 613:617 vitro 613:617 In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. 2813359 7 4 theme biological 1339:1348 arg1 activity 1350:1357 in vivo biological activity 1331:1357 in vivo biological activity of EPO 1331:1364 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 5 5 theme sugar 816:820 arg1 chains 822:827 their N-linked sugar chains 801:827 their N-linked sugar chains 801:827 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 2 6 theme recombinant 525:535 arg1 EPO 543:545 the previously described recombinant human EPO 500:545 the previously described recombinant human EPO (standard EPO) 500:560 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 2 6 theme recombinant 525:535 arg1 EPO 557:559 standard EPO 548:559 standard EPO 548:559 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 7 7 theme in 1331:1332 arg1 activity 1350:1357 in vivo biological activity 1331:1357 in vivo biological activity of EPO 1331:1364 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 0 8 theme ovary 131:135 arg1 cells 137:141 Chinese hamster ovary cells 115:141 Chinese hamster ovary cells 115:141 Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. 2813359 5 9 theme major 998:1002 arg1 chain 1010:1014 the major sugar chain 994:1014 the major sugar chain 994:1014 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 9 theme major 998:1002 arg1 type 986:989 the tetraantennary complex type 959:989 the tetraantennary complex type 959:989 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 1 10 theme different 200:208 arg1 activities 221:230 different biological activities 200:230 different biological activities 200:230 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 2 11 theme standard 548:555 arg1 EPO 543:545 the previously described recombinant human EPO 500:545 the previously described recombinant human EPO (standard EPO) 500:560 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 2 11 theme standard 548:555 arg1 EPO 557:559 standard EPO 548:559 standard EPO 548:559 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 2 12 from times 466:470 arg1 activity 488:495 vitro activity 482:495 vitro activity of the previously described recombinant human EPO (standard EPO) 482:560 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 6 13 theme EPO 1148:1150 arg1 ratio 1160:1164 the ratio 1156:1164 the ratio of tetraantennary to biantennary oligosaccharides 1156:1214 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 6 13 theme EPO 1148:1150 arg1 activity 1136:1143 the in vivo activity 1124:1143 the in vivo activity of EPO 1124:1150 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 6 14 dep in 1128:1129 arg1 vivo 1131:1134 vivo 1131:1134 vivo 1131:1134 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 5 15 theme complex 978:984 arg1 chain 1010:1014 the major sugar chain 994:1014 the major sugar chain 994:1014 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 15 theme complex 978:984 arg1 type 986:989 the tetraantennary complex type 959:989 the tetraantennary complex type 959:989 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 2 16 theme EPO 543:545 arg1 activity 488:495 vitro activity 482:495 vitro activity of the previously described recombinant human EPO (standard EPO) 482:560 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 5 17 contain contains 850:857 arg2 type 883:886 the biantennary complex type 859:886 the biantennary complex type 859:886 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 17 contain contains 850:857 arg2 chain 907:911 the major sugar chain 891:911 the major sugar chain 891:911 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 17 contain contains 850:857 arg1 EPO-bi 843:848 EPO-bi 843:848 EPO-bi 843:848 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 18 theme complex 875:881 arg1 chain 907:911 the major sugar chain 891:911 the major sugar chain 891:911 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 18 theme complex 875:881 arg1 type 883:886 the biantennary complex type 859:886 the biantennary complex type 859:886 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 6 19 theme in 1128:1129 arg1 activity 1136:1143 the in vivo activity 1124:1143 the in vivo activity of EPO 1124:1150 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 2 20 theme 3 464:464 arg1 times 466:470 times 466:470 times 466:470 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 0 21 theme human 82:86 arg1 erythropoietin 88:101 recombinant human erythropoietin 70:101 recombinant human erythropoietin 70:101 Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. 2813359 4 22 theme standard 698:705 arg1 EPO 707:709 the standard EPO 694:709 the standard EPO 694:709 EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. 2813359 1 23 theme human 343:347 arg1 gene 364:367 the human erythropoietin gene 339:367 the human erythropoietin gene 339:367 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 2 24 theme vitro 482:486 arg1 activity 488:495 vitro activity 482:495 vitro activity of the previously described recombinant human EPO (standard EPO) 482:560 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 0 25 theme Chinese 115:121 arg1 cells 137:141 Chinese hamster ovary cells 115:141 Chinese hamster ovary cells 115:141 Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. 2813359 7 26 dep in 1331:1332 arg1 vivo 1334:1337 vivo 1334:1337 vivo 1334:1337 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 7 27 theme N-linked 1268:1275 arg1 chains 1283:1288 the N-linked sugar chains 1264:1288 the N-linked sugar chains 1264:1288 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 2 28 theme one-seventh 427:437 arg1 activity 451:458 in vivo activity 443:458 in vivo activity 443:458 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 1 29 theme recombinant 275:285 arg1 line 314:317 a recombinant Chinese hamster ovary cell line 273:317 a recombinant Chinese hamster ovary cell line 273:317 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 29 theme recombinant 275:285 arg1 B8-300 320:325 B8-300 320:325 B8-300 320:325 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 7 30 theme sugar 1277:1281 arg1 chains 1283:1288 the N-linked sugar chains 1264:1288 the N-linked sugar chains 1264:1288 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 0 31 theme sugar 21:25 arg1 structure 33:41 sugar chain structure 21:41 sugar chain structure 21:41 Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. 2813359 1 32 theme hamster 295:301 arg1 line 314:317 a recombinant Chinese hamster ovary cell line 273:317 a recombinant Chinese hamster ovary cell line 273:317 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 32 theme hamster 295:301 arg1 B8-300 320:325 B8-300 320:325 B8-300 320:325 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 5 33 theme major 895:899 arg1 chain 907:911 the major sugar chain 891:911 the major sugar chain 891:911 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 33 theme major 895:899 arg1 type 883:886 the biantennary complex type 859:886 the biantennary complex type 859:886 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 7 34 theme higher 1244:1249 arg1 branching 1251:1259 higher branching 1244:1259 higher branching of the N-linked sugar chains 1244:1288 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 1 35 theme cell 309:312 arg1 line 314:317 a recombinant Chinese hamster ovary cell line 273:317 a recombinant Chinese hamster ovary cell line 273:317 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 35 theme cell 309:312 arg1 B8-300 320:325 B8-300 320:325 B8-300 320:325 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 2 36 theme in 443:444 arg1 activity 451:458 in vivo activity 443:458 in vivo activity 443:458 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 3 37 theme in 598:599 arg1 activities 619:628 both in vivo and in vitro activities 593:628 both in vivo and in vitro activities comparable to those of the standard EPO 593:668 In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. 2813359 0 38 theme biological 47:56 arg1 activity 58:65 biological activity 47:65 biological activity 47:65 Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. 2813359 6 39 theme tetraantennary 1169:1182 arg1 ratio 1160:1164 the ratio 1156:1164 the ratio of tetraantennary to biantennary oligosaccharides 1156:1214 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 6 39 theme tetraantennary 1169:1182 arg1 activity 1136:1143 the in vivo activity 1124:1143 the in vivo activity of EPO 1124:1150 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 6 40 theme recombinant 1061:1071 arg1 EPO 1079:1081 recombinant human EPO 1061:1081 recombinant human EPO 1061:1081 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 3 41 theme comparable 630:639 arg1 activities 619:628 both in vivo and in vitro activities 593:628 both in vivo and in vitro activities comparable to those of the standard EPO 593:668 In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. 2813359 4 42 theme same 719:722 arg1 composition 735:745 the same amino acid composition 715:745 the same amino acid composition 715:745 EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. 2813359 2 43 dep times 466:470 arg1 higher 472:477 higher 472:477 higher 472:477 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 6 44 theme preparations 1045:1056 arg1 examination 1022:1032 examination 1022:1032 examination of various preparations of recombinant human EPO 1022:1081 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 5 45 contain contain 951:957 arg1 EPO-tetra 920:928 EPO-tetra 920:928 EPO-tetra 920:928 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 45 contain contain 951:957 arg2 chain 1010:1014 the major sugar chain 994:1014 the major sugar chain 994:1014 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 45 contain contain 951:957 arg1 EPO 947:949 the standard EPO 934:949 the standard EPO 934:949 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 45 contain contain 951:957 arg2 type 986:989 the tetraantennary complex type 959:989 the tetraantennary complex type 959:989 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 4 46 theme acid 730:733 arg1 composition 735:745 the same amino acid composition 715:745 the same amino acid composition 715:745 EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. 2813359 5 47 theme standard 938:945 arg1 EPO 947:949 the standard EPO 934:949 the standard EPO 934:949 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 1 48 theme culture 255:261 arg1 medium 263:268 the culture medium 251:268 the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced 251:387 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 2 49 dep in 443:444 arg1 vivo 446:449 vivo 446:449 vivo 446:449 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 1 50 theme EPO-tetra 184:192 arg1 forms 148:152 Two forms 144:152 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities 144:230 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 51 theme EPO-bi 173:178 arg1 forms 148:152 Two forms 144:152 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities 144:230 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 7 52 theme EPO 1362:1364 arg1 activity 1350:1357 in vivo biological activity 1331:1357 in vivo biological activity of EPO 1331:1364 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 5 53 theme N-linked 807:814 arg1 chains 822:827 their N-linked sugar chains 801:827 their N-linked sugar chains 801:827 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 7 54 link N-linked 1268:1275 arg1 chains 1283:1288 the N-linked sugar chains 1264:1288 the N-linked sugar chains 1264:1288 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 7 55 theme activity 1350:1357 arg1 expression 1317:1326 effective expression 1307:1326 effective expression of in vivo biological activity of EPO 1307:1364 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 5 56 theme tetraantennary 963:976 arg1 chain 1010:1014 the major sugar chain 994:1014 the major sugar chain 994:1014 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 56 theme tetraantennary 963:976 arg1 type 986:989 the tetraantennary complex type 959:989 the tetraantennary complex type 959:989 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 2 57 theme described 515:523 arg1 EPO 543:545 the previously described recombinant human EPO 500:545 the previously described recombinant human EPO (standard EPO) 500:560 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 2 57 theme described 515:523 arg1 EPO 557:559 standard EPO 548:559 standard EPO 548:559 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 6 58 theme EPO 1079:1081 arg1 preparations 1045:1056 various preparations 1037:1056 various preparations of recombinant human EPO 1037:1081 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 5 59 theme sugar 1004:1008 arg1 chain 1010:1014 the major sugar chain 994:1014 the major sugar chain 994:1014 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 59 theme sugar 1004:1008 arg1 type 986:989 the tetraantennary complex type 959:989 the tetraantennary complex type 959:989 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 1 60 attach isolated 237:244 arg1 medium 263:268 the culture medium 251:268 the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced 251:387 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 60 attach isolated 237:244 arg2 forms 148:152 Two forms 144:152 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities 144:230 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 5 61 theme structural 778:787 arg1 analyses 789:796 structural analyses 778:796 structural analyses of their N-linked sugar chains 778:827 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 4 62 contain had 711:713 arg1 EPO 707:709 the standard EPO 694:709 the standard EPO 694:709 EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. 2813359 4 62 contain had 711:713 arg2 immunoreactivity 751:766 immunoreactivity 751:766 immunoreactivity 751:766 EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. 2813359 4 62 contain had 711:713 arg1 EPO-tetra 679:687 EPO-tetra 679:687 EPO-tetra 679:687 EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. 2813359 4 62 contain had 711:713 arg2 composition 735:745 the same amino acid composition 715:745 the same amino acid composition 715:745 EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. 2813359 4 62 contain had 711:713 arg1 EPO-bi 671:676 EPO-bi 671:676 EPO-bi 671:676 EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. 2813359 7 63 theme effective 1307:1315 arg1 expression 1317:1326 effective expression 1307:1326 effective expression of in vivo biological activity of EPO 1307:1364 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 5 64 theme biantennary 863:873 arg1 chain 907:911 the major sugar chain 891:911 the major sugar chain 891:911 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 64 theme biantennary 863:873 arg1 type 883:886 the biantennary complex type 859:886 the biantennary complex type 859:886 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 2 65 theme human 537:541 arg1 EPO 543:545 the previously described recombinant human EPO 500:545 the previously described recombinant human EPO (standard EPO) 500:560 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 2 65 theme human 537:541 arg1 EPO 557:559 standard EPO 548:559 standard EPO 548:559 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 0 66 theme recombinant 70:80 arg1 erythropoietin 88:101 recombinant human erythropoietin 70:101 recombinant human erythropoietin 70:101 Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. 2813359 5 67 theme chains 822:827 arg1 analyses 789:796 structural analyses 778:796 structural analyses of their N-linked sugar chains 778:827 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 7 68 theme chains 1283:1288 arg1 branching 1251:1259 higher branching 1244:1259 higher branching of the N-linked sugar chains 1244:1288 These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. 2813359 0 69 theme erythropoietin 88:101 arg1 structure 33:41 sugar chain structure 21:41 sugar chain structure 21:41 Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. 2813359 0 69 theme erythropoietin 88:101 arg1 activity 58:65 biological activity 47:65 biological activity 47:65 Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. 2813359 1 70 with erythropoietin 157:170 arg1 activities 221:230 different biological activities 200:230 different biological activities 200:230 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 71 theme erythropoietin 157:170 arg1 forms 148:152 Two forms 144:152 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities 144:230 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 2 72 dep activity 451:458 arg1 the 439:441 the 439:441 the 439:441 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 5 73 theme sugar 901:905 arg1 chain 907:911 the major sugar chain 891:911 the major sugar chain 891:911 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 5 73 theme sugar 901:905 arg1 type 883:886 the biantennary complex type 859:886 the biantennary complex type 859:886 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 0 74 theme hamster 123:129 arg1 cells 137:141 Chinese hamster ovary cells 115:141 Chinese hamster ovary cells 115:141 Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. 2813359 1 75 theme erythropoietin 349:362 arg1 gene 364:367 the human erythropoietin gene 339:367 the human erythropoietin gene 339:367 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 5 76 link N-linked 807:814 arg1 chains 822:827 their N-linked sugar chains 801:827 their N-linked sugar chains 801:827 However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. 2813359 2 77 from activity 451:458 arg1 activity 488:495 vitro activity 482:495 vitro activity of the previously described recombinant human EPO (standard EPO) 482:560 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 0 78 theme chain 27:31 arg1 structure 33:41 sugar chain structure 21:41 sugar chain structure 21:41 Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. 2813359 1 79 theme Chinese 287:293 arg1 line 314:317 a recombinant Chinese hamster ovary cell line 273:317 a recombinant Chinese hamster ovary cell line 273:317 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 79 theme Chinese 287:293 arg1 B8-300 320:325 B8-300 320:325 B8-300 320:325 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 2 80 theme unusual 401:407 arg1 EPO-bi 390:395 EPO-bi 390:395 EPO-bi 390:395 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 2 80 theme unusual 401:407 arg1 form 409:412 an unusual form 398:412 an unusual form 398:412 EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). 2813359 1 81 theme ovary 303:307 arg1 line 314:317 a recombinant Chinese hamster ovary cell line 273:317 a recombinant Chinese hamster ovary cell line 273:317 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 81 theme ovary 303:307 arg1 B8-300 320:325 B8-300 320:325 B8-300 320:325 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 82 theme biological 210:219 arg1 activities 221:230 different biological activities 200:230 different biological activities 200:230 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 83 theme line 314:317 arg1 medium 263:268 the culture medium 251:268 the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced 251:387 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 1 84 with EPO-tetra 184:192 arg1 activities 221:230 different biological activities 200:230 different biological activities 200:230 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 6 85 theme human 1073:1077 arg1 EPO 1079:1081 recombinant human EPO 1061:1081 recombinant human EPO 1061:1081 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 1 86 with EPO-bi 173:178 arg1 activities 221:230 different biological activities 200:230 different biological activities 200:230 Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. 2813359 3 87 theme in 610:611 arg1 activities 619:628 both in vivo and in vitro activities 593:628 both in vivo and in vitro activities comparable to those of the standard EPO 593:668 In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. 2813359 3 88 dep in 598:599 arg1 vivo 601:604 vivo 601:604 vivo 601:604 In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. 2813359 6 89 theme various 1037:1043 arg1 preparations 1045:1056 various preparations 1037:1056 various preparations of recombinant human EPO 1037:1081 From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. 2813359 4 90 theme amino 724:728 arg1 composition 735:745 the same amino acid composition 715:745 the same amino acid composition 715:745 EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. 10764830 4 0 theme CHO 642:644 arg1 cells 646:650 The parental CHO cells 629:650 The parental CHO cells 629:650 The parental CHO cells produced IFN-gamma with biantennary sugar chains mainly. 10764830 5 1 theme GnT-IV 718:723 arg1 activity 725:732 the GnT-IV activity 714:732 the GnT-IV activity 714:732 When the GnT-IV activity was increased, triantennary sugar chains with a branch produced by GnT-IV increased up to 66.9% of the total sugar chains. 10764830 3 2 theme hamster 576:582 arg1 cells 596:600 Chinese hamster ovary (CHO) cells 568:600 Chinese hamster ovary (CHO) cells producing human IFN-gamma 568:626 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 8 3 theme multiantennary 1160:1173 arg1 chains 1181:1186 these multiantennary sugar chains 1154:1186 these multiantennary sugar chains 1154:1186 The proportion of these multiantennary sugar chains corresponded to the intracellular activities of GnT-IV and -V. 10764830 6 4 dep 55.7 966:969 arg1 to 963:964 to 963:964 to 963:964 When the GnT-V activity was increased, triantennary sugar chains with a corresponding branch increased up to 55.7% of the total sugar chains. 10764830 7 5 theme total 1116:1120 arg1 chains 1128:1133 the total sugar chains 1112:1133 the total sugar chains 1112:1133 When the GnT-IV and -V activities were increased at a time, tetraantennary sugar chains increased up to 56.2% of the total sugar chains. 10764830 9 6 theme secretory 1416:1424 arg1 glycoproteins 1426:1438 the secretory glycoproteins 1412:1438 the secretory glycoproteins 1412:1438 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 8 7 theme chains 1181:1186 arg1 proportion 1140:1149 The proportion 1136:1149 The proportion of these multiantennary sugar chains 1136:1186 The proportion of these multiantennary sugar chains corresponded to the intracellular activities of GnT-IV and -V. 10764830 6 8 theme corresponding 929:941 arg1 branch 943:948 a corresponding branch 927:948 a corresponding branch 927:948 When the GnT-V activity was increased, triantennary sugar chains with a corresponding branch increased up to 55.7% of the total sugar chains. 10764830 2 9 gly glycoprotein 272:283 arg1 IFN-gamma 251:259 IFN-gamma 251:259 IFN-gamma 251:259 We attempted to remodel the sugar chain structures using IFN-gamma as a model glycoprotein. 10764830 2 9 gly glycoprotein 272:283 arg1 glycoprotein 272:283 a model glycoprotein 264:283 a model glycoprotein 264:283 We attempted to remodel the sugar chain structures using IFN-gamma as a model glycoprotein. 10764830 2 10 theme model 266:270 arg1 IFN-gamma 251:259 IFN-gamma 251:259 IFN-gamma 251:259 We attempted to remodel the sugar chain structures using IFN-gamma as a model glycoprotein. 10764830 2 10 theme model 266:270 arg1 glycoprotein 272:283 a model glycoprotein 264:283 a model glycoprotein 264:283 We attempted to remodel the sugar chain structures using IFN-gamma as a model glycoprotein. 10764830 1 11 theme multiantennary 167:180 arg1 structures 182:191 multiantennary structures 167:191 multiantennary structures 167:191 Natural human interferon (IFN)-gamma has mainly biantennary complex-type sugar chains and scarcely has multiantennary structures. 10764830 11 12 theme therapeutics 1788:1799 arg1 potency 1764:1770 the potency 1760:1770 the potency of glycoprotein therapeutics 1760:1799 This technology can produce glycoforms out of natural occurrence, which should enlarge the potency of glycoprotein therapeutics. 10764830 7 13 theme chains 1128:1133 arg1 % 1107:1107 up to 56.2% 1097:1107 up to 56.2% of the total sugar chains 1097:1133 When the GnT-IV and -V activities were increased at a time, tetraantennary sugar chains increased up to 56.2% of the total sugar chains. 10764830 7 13 theme chains 1128:1133 arg1 chains 1128:1133 the total sugar chains 1112:1133 the total sugar chains 1112:1133 When the GnT-IV and -V activities were increased at a time, tetraantennary sugar chains increased up to 56.2% of the total sugar chains. 10764830 8 14 theme intracellular 1208:1220 arg1 activities 1222:1231 the intracellular activities 1204:1231 the intracellular activities of GnT-IV and -V 1204:1248 The proportion of these multiantennary sugar chains corresponded to the intracellular activities of GnT-IV and -V. 10764830 5 15 dep 66.9 824:827 arg1 to 821:822 to 821:822 to 821:822 When the GnT-IV activity was increased, triantennary sugar chains with a branch produced by GnT-IV increased up to 66.9% of the total sugar chains. 10764830 10 16 theme branching 1559:1567 arg1 structure 1569:1577 the branching structure 1555:1577 the branching structure of sugar chains of glycoproteins 1555:1610 The results suggest that the branching structure of sugar chains of glycoproteins could be controlled by cellular GnT-IV and GnT-V activities. 10764830 6 17 theme sugar 985:989 arg1 chains 991:996 the total sugar chains 975:996 the total sugar chains 975:996 When the GnT-V activity was increased, triantennary sugar chains with a corresponding branch increased up to 55.7% of the total sugar chains. 10764830 9 18 gly glycoproteins 1426:1438 arg1 glycoproteins 1426:1438 the secretory glycoproteins 1412:1438 the secretory glycoproteins 1412:1438 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 7 19 dep 56.2 1103:1106 arg1 to 1100:1101 to 1100:1101 to 1100:1101 When the GnT-IV and -V activities were increased at a time, tetraantennary sugar chains increased up to 56.2% of the total sugar chains. 10764830 2 20 theme chain 228:232 arg1 structures 234:243 the sugar chain structures 218:243 the sugar chain structures using IFN-gamma as a model glycoprotein 218:283 We attempted to remodel the sugar chain structures using IFN-gamma as a model glycoprotein. 10764830 9 21 theme cellular 1464:1471 arg1 proteins 1473:1480 almost CHO cellular proteins 1453:1480 almost CHO cellular proteins 1453:1480 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 3 22 theme branching 300:308 arg1 glycoforms 310:319 the branching glycoforms 296:319 the branching glycoforms of IFN-gamma 296:332 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 10 23 theme chains 1588:1593 arg1 structure 1569:1577 the branching structure 1555:1577 the branching structure of sugar chains of glycoproteins 1555:1610 The results suggest that the branching structure of sugar chains of glycoproteins could be controlled by cellular GnT-IV and GnT-V activities. 10764830 7 24 theme tetraantennary 1059:1072 arg1 chains 1080:1085 tetraantennary sugar chains 1059:1085 tetraantennary sugar chains 1059:1085 When the GnT-IV and -V activities were increased at a time, tetraantennary sugar chains increased up to 56.2% of the total sugar chains. 10764830 4 25 with IFN-gamma 661:669 arg1 chains 694:699 biantennary sugar chains 676:699 biantennary sugar chains 676:699 The parental CHO cells produced IFN-gamma with biantennary sugar chains mainly. 10764830 5 26 theme sugar 762:766 arg1 chains 768:773 triantennary sugar chains 749:773 triantennary sugar chains with a branch produced by GnT-IV 749:806 When the GnT-IV activity was increased, triantennary sugar chains with a branch produced by GnT-IV increased up to 66.9% of the total sugar chains. 10764830 9 27 theme lectin 1265:1270 arg1 blot 1272:1275 lectin blot and flow cytometric analysis 1265:1304 blot 1272:1275 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 1 28 theme complex-type 124:135 arg1 chains 143:148 complex-type sugar chains 124:148 complex-type sugar chains 124:148 Natural human interferon (IFN)-gamma has mainly biantennary complex-type sugar chains and scarcely has multiantennary structures. 10764830 11 29 theme natural 1719:1725 arg1 occurrence 1727:1736 natural occurrence 1719:1736 natural occurrence 1719:1736 This technology can produce glycoforms out of natural occurrence, which should enlarge the potency of glycoprotein therapeutics. 10764830 3 30 dep GnT-IV 363:368 arg1 UDP-N-acetylglucosamine 371:393 UDP-N-acetylglucosamine 371:393 UDP-N-acetylglucosamine 371:393 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 3 30 dep GnT-IV 363:368 arg1 4-N-acetylglucosaminyltransferase 425:457 4-N-acetylglucosaminyltransferase 425:457 4-N-acetylglucosaminyltransferase 425:457 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 9 31 theme cytometric 1286:1295 arg1 analysis 1297:1304 lectin blot and flow cytometric analysis 1265:1304 analysis 1297:1304 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 3 32 dep UDP-N-acetylglucosamine 371:393 arg1 beta-1 417:422 alpha-1,3-D-mannoside beta-1 395:422 alpha-1,3-D-mannoside beta-1 395:422 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 1 33 theme Natural 64:70 arg1 -gamma 94:99 Natural human interferon (IFN)-gamma 64:99 Natural human interferon (IFN)-gamma 64:99 Natural human interferon (IFN)-gamma has mainly biantennary complex-type sugar chains and scarcely has multiantennary structures. 10764830 10 34 theme cellular 1635:1642 arg1 activities 1661:1670 cellular GnT-IV and GnT-V activities 1635:1670 cellular GnT-IV and GnT-V activities 1635:1670 The results suggest that the branching structure of sugar chains of glycoproteins could be controlled by cellular GnT-IV and GnT-V activities. 10764830 1 35 theme interferon 78:87 arg1 -gamma 94:99 Natural human interferon (IFN)-gamma 64:99 Natural human interferon (IFN)-gamma 64:99 Natural human interferon (IFN)-gamma has mainly biantennary complex-type sugar chains and scarcely has multiantennary structures. 10764830 1 36 theme IFN 90:92 arg1 -gamma 94:99 Natural human interferon (IFN)-gamma 64:99 Natural human interferon (IFN)-gamma 64:99 Natural human interferon (IFN)-gamma has mainly biantennary complex-type sugar chains and scarcely has multiantennary structures. 10764830 3 37 theme alpha-1,6-D-mannoside 498:518 arg1 beta-1 520:525 alpha-1,6-D-mannoside beta-1 498:525 alpha-1,6-D-mannoside beta-1 498:525 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 0 38 theme sugar 14:18 arg1 structures 26:35 sugar chain structures 14:35 sugar chain structures of human interferon-gamma 14:61 Remodeling of sugar chain structures of human interferon-gamma. 10764830 0 39 theme structures 26:35 arg1 Remodeling 0:9 Remodeling 0:9 Remodeling of sugar chain structures of human interferon-gamma 0:61 Remodeling of sugar chain structures of human interferon-gamma. 10764830 9 40 theme chains 1361:1366 arg1 structure 1338:1346 the multi-branch structure 1321:1346 the multi-branch structure of the sugar chains 1321:1366 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 6 41 theme triantennary 896:907 arg1 chains 915:920 triantennary sugar chains 896:920 triantennary sugar chains with a corresponding branch 896:948 When the GnT-V activity was increased, triantennary sugar chains with a corresponding branch increased up to 55.7% of the total sugar chains. 10764830 3 42 theme alpha-1,3-D-mannoside 395:415 arg1 beta-1 417:422 alpha-1,3-D-mannoside beta-1 395:422 alpha-1,3-D-mannoside beta-1 395:422 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 1 43 contain has 163:165 arg2 structures 182:191 multiantennary structures 167:191 multiantennary structures 167:191 Natural human interferon (IFN)-gamma has mainly biantennary complex-type sugar chains and scarcely has multiantennary structures. 10764830 1 43 contain has 163:165 arg1 -gamma 94:99 Natural human interferon (IFN)-gamma 64:99 Natural human interferon (IFN)-gamma 64:99 Natural human interferon (IFN)-gamma has mainly biantennary complex-type sugar chains and scarcely has multiantennary structures. 10764830 5 44 theme sugar 843:847 arg1 chains 849:854 the total sugar chains 833:854 the total sugar chains 833:854 When the GnT-IV activity was increased, triantennary sugar chains with a branch produced by GnT-IV increased up to 66.9% of the total sugar chains. 10764830 11 45 gly glycoprotein 1775:1786 arg1 glycoprotein 1775:1786 glycoprotein therapeutics 1775:1799 glycoprotein therapeutics 1775:1799 This technology can produce glycoforms out of natural occurrence, which should enlarge the potency of glycoprotein therapeutics. 10764830 3 46 theme ovary 584:588 arg1 cells 596:600 Chinese hamster ovary (CHO) cells 568:600 Chinese hamster ovary (CHO) cells producing human IFN-gamma 568:626 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 0 47 theme interferon-gamma 46:61 arg1 structures 26:35 sugar chain structures 14:35 sugar chain structures of human interferon-gamma 14:61 Remodeling of sugar chain structures of human interferon-gamma. 10764830 4 48 theme biantennary 676:686 arg1 chains 694:699 biantennary sugar chains 676:699 biantennary sugar chains 676:699 The parental CHO cells produced IFN-gamma with biantennary sugar chains mainly. 10764830 7 49 theme sugar 1122:1126 arg1 chains 1128:1133 the total sugar chains 1112:1133 the total sugar chains 1112:1133 When the GnT-IV and -V activities were increased at a time, tetraantennary sugar chains increased up to 56.2% of the total sugar chains. 10764830 3 50 theme Chinese 568:574 arg1 cells 596:600 Chinese hamster ovary (CHO) cells 568:600 Chinese hamster ovary (CHO) cells producing human IFN-gamma 568:626 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 4 51 theme parental 633:640 arg1 cells 646:650 The parental CHO cells 629:650 The parental CHO cells 629:650 The parental CHO cells produced IFN-gamma with biantennary sugar chains mainly. 10764830 3 52 theme CHO 591:593 arg1 cells 596:600 Chinese hamster ovary (CHO) cells 568:600 Chinese hamster ovary (CHO) cells producing human IFN-gamma 568:626 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 9 53 theme glycoproteins 1426:1438 arg1 IFN-gamma 1394:1402 IFN-gamma 1394:1402 IFN-gamma 1394:1402 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 9 53 theme glycoproteins 1426:1438 arg1 glycoproteins 1426:1438 the secretory glycoproteins 1412:1438 the secretory glycoproteins 1412:1438 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 9 53 theme glycoproteins 1426:1438 arg1 one 1405:1407 one 1405:1407 one 1405:1407 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 8 54 theme sugar 1175:1179 arg1 chains 1181:1186 these multiantennary sugar chains 1154:1186 these multiantennary sugar chains 1154:1186 The proportion of these multiantennary sugar chains corresponded to the intracellular activities of GnT-IV and -V. 10764830 8 55 theme -V 1247:1248 arg1 activities 1222:1231 the intracellular activities 1204:1231 the intracellular activities of GnT-IV and -V 1204:1248 The proportion of these multiantennary sugar chains corresponded to the intracellular activities of GnT-IV and -V. 10764830 10 56 theme sugar 1582:1586 arg1 chains 1588:1593 sugar chains 1582:1593 sugar chains of glycoproteins 1582:1610 The results suggest that the branching structure of sugar chains of glycoproteins could be controlled by cellular GnT-IV and GnT-V activities. 10764830 0 57 theme human 40:44 arg1 interferon-gamma 46:61 human interferon-gamma 40:61 human interferon-gamma 40:61 Remodeling of sugar chain structures of human interferon-gamma. 10764830 3 58 theme human 612:616 arg1 IFN-gamma 618:626 human IFN-gamma 612:626 human IFN-gamma 612:626 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 6 59 theme chains 991:996 arg1 chains 991:996 the total sugar chains 975:996 the total sugar chains 975:996 When the GnT-V activity was increased, triantennary sugar chains with a corresponding branch increased up to 55.7% of the total sugar chains. 10764830 6 59 theme chains 991:996 arg1 % 970:970 up to 55.7% 960:970 up to 55.7% of the total sugar chains 960:996 When the GnT-V activity was increased, triantennary sugar chains with a corresponding branch increased up to 55.7% of the total sugar chains. 10764830 11 60 theme glycoprotein 1775:1786 arg1 therapeutics 1788:1799 glycoprotein therapeutics 1775:1799 glycoprotein therapeutics 1775:1799 This technology can produce glycoforms out of natural occurrence, which should enlarge the potency of glycoprotein therapeutics. 10764830 7 61 theme sugar 1074:1078 arg1 chains 1080:1085 tetraantennary sugar chains 1059:1085 tetraantennary sugar chains 1059:1085 When the GnT-IV and -V activities were increased at a time, tetraantennary sugar chains increased up to 56.2% of the total sugar chains. 10764830 9 62 theme CHO 1460:1462 arg1 proteins 1473:1480 almost CHO cellular proteins 1453:1480 almost CHO cellular proteins 1453:1480 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 6 63 theme total 979:983 arg1 chains 991:996 the total sugar chains 975:996 the total sugar chains 975:996 When the GnT-V activity was increased, triantennary sugar chains with a corresponding branch increased up to 55.7% of the total sugar chains. 10764830 2 64 theme sugar 222:226 arg1 structures 234:243 the sugar chain structures 218:243 the sugar chain structures using IFN-gamma as a model glycoprotein 218:283 We attempted to remodel the sugar chain structures using IFN-gamma as a model glycoprotein. 10764830 8 65 theme GnT-IV 1236:1241 arg1 activities 1222:1231 the intracellular activities 1204:1231 the intracellular activities of GnT-IV and -V 1204:1248 The proportion of these multiantennary sugar chains corresponded to the intracellular activities of GnT-IV and -V. 10764830 5 66 theme triantennary 749:760 arg1 chains 768:773 triantennary sugar chains 749:773 triantennary sugar chains with a branch produced by GnT-IV 749:806 When the GnT-IV activity was increased, triantennary sugar chains with a branch produced by GnT-IV increased up to 66.9% of the total sugar chains. 10764830 7 67 theme -V 1019:1020 arg1 activities 1022:1031 the GnT-IV and -V activities 1004:1031 the GnT-IV and -V activities 1004:1031 When the GnT-IV and -V activities were increased at a time, tetraantennary sugar chains increased up to 56.2% of the total sugar chains. 10764830 1 68 theme sugar 137:141 arg1 chains 143:148 complex-type sugar chains 124:148 complex-type sugar chains 124:148 Natural human interferon (IFN)-gamma has mainly biantennary complex-type sugar chains and scarcely has multiantennary structures. 10764830 9 69 theme flow 1281:1284 arg1 analysis 1297:1304 lectin blot and flow cytometric analysis 1265:1304 analysis 1297:1304 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 7 70 theme GnT-IV 1008:1013 arg1 activities 1022:1031 the GnT-IV and -V activities 1004:1031 the GnT-IV and -V activities 1004:1031 When the GnT-IV and -V activities were increased at a time, tetraantennary sugar chains increased up to 56.2% of the total sugar chains. 10764830 3 71 theme IFN-gamma 324:332 arg1 glycoforms 310:319 the branching glycoforms 296:319 the branching glycoforms of IFN-gamma 296:332 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 10 72 gly glycoproteins 1598:1610 arg1 glycoproteins 1598:1610 glycoproteins 1598:1610 glycoproteins 1598:1610 The results suggest that the branching structure of sugar chains of glycoproteins could be controlled by cellular GnT-IV and GnT-V activities. 10764830 9 73 theme GnT 1519:1521 arg1 genes 1523:1527 the GnT genes 1515:1527 the GnT genes 1515:1527 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 1 74 theme human 72:76 arg1 -gamma 94:99 Natural human interferon (IFN)-gamma 64:99 Natural human interferon (IFN)-gamma 64:99 Natural human interferon (IFN)-gamma has mainly biantennary complex-type sugar chains and scarcely has multiantennary structures. 10764830 5 75 theme chains 849:854 arg1 chains 849:854 the total sugar chains 833:854 the total sugar chains 833:854 When the GnT-IV activity was increased, triantennary sugar chains with a branch produced by GnT-IV increased up to 66.9% of the total sugar chains. 10764830 5 75 theme chains 849:854 arg1 % 828:828 up to 66.9% 818:828 up to 66.9% of the total sugar chains 818:854 When the GnT-IV activity was increased, triantennary sugar chains with a branch produced by GnT-IV increased up to 66.9% of the total sugar chains. 10764830 9 76 theme multi-branch 1325:1336 arg1 structure 1338:1346 the multi-branch structure 1321:1346 the multi-branch structure of the sugar chains 1321:1366 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 6 77 with chains 915:920 arg1 branch 943:948 a corresponding branch 927:948 a corresponding branch 927:948 When the GnT-V activity was increased, triantennary sugar chains with a corresponding branch increased up to 55.7% of the total sugar chains. 10764830 0 78 theme chain 20:24 arg1 structures 26:35 sugar chain structures 14:35 sugar chain structures of human interferon-gamma 14:61 Remodeling of sugar chain structures of human interferon-gamma. 10764830 10 79 theme GnT-V 1655:1659 arg1 activities 1661:1670 cellular GnT-IV and GnT-V activities 1635:1670 cellular GnT-IV and GnT-V activities 1635:1670 The results suggest that the branching structure of sugar chains of glycoproteins could be controlled by cellular GnT-IV and GnT-V activities. 10764830 9 80 theme sugar 1355:1359 arg1 chains 1361:1366 the sugar chains 1351:1366 the sugar chains 1351:1366 What is more, lectin blot and flow cytometric analysis indicated that the multi-branch structure of the sugar chains was increased not only on IFN-gamma, one of the secretory glycoproteins, but also on almost CHO cellular proteins by introducing either or both of the GnT genes. 10764830 6 81 theme sugar 909:913 arg1 chains 915:920 triantennary sugar chains 896:920 triantennary sugar chains with a corresponding branch 896:948 When the GnT-V activity was increased, triantennary sugar chains with a corresponding branch increased up to 55.7% of the total sugar chains. 10764830 5 82 with chains 768:773 arg1 branch 782:787 a branch 780:787 a branch produced by GnT-IV 780:806 When the GnT-IV activity was increased, triantennary sugar chains with a branch produced by GnT-IV increased up to 66.9% of the total sugar chains. 10764830 10 83 theme glycoproteins 1598:1610 arg1 chains 1588:1593 sugar chains 1582:1593 sugar chains of glycoproteins 1582:1610 The results suggest that the branching structure of sugar chains of glycoproteins could be controlled by cellular GnT-IV and GnT-V activities. 10764830 10 84 theme GnT-IV 1644:1649 arg1 activities 1661:1670 cellular GnT-IV and GnT-V activities 1635:1670 cellular GnT-IV and GnT-V activities 1635:1670 The results suggest that the branching structure of sugar chains of glycoproteins could be controlled by cellular GnT-IV and GnT-V activities. 10764830 5 85 theme total 837:841 arg1 chains 849:854 the total sugar chains 833:854 the total sugar chains 833:854 When the GnT-IV activity was increased, triantennary sugar chains with a branch produced by GnT-IV increased up to 66.9% of the total sugar chains. 10764830 3 86 dep GnT-V 467:471 arg1 6-N-acetylglucosaminyltransferase 528:560 6-N-acetylglucosaminyltransferase 528:560 6-N-acetylglucosaminyltransferase 528:560 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 3 86 dep GnT-V 467:471 arg1 UDP-N-acetylglucosamine 474:496 UDP-N-acetylglucosamine 474:496 UDP-N-acetylglucosamine 474:496 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 3 87 dep UDP-N-acetylglucosamine 474:496 arg1 beta-1 520:525 alpha-1,6-D-mannoside beta-1 498:525 alpha-1,6-D-mannoside beta-1 498:525 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 3 88 gly glycoforms 310:319 arg1 IFN-gamma 324:332 IFN-gamma 324:332 IFN-gamma 324:332 To obtain the branching glycoforms of IFN-gamma, we introduced the genes for GnT-IV (UDP-N-acetylglucosamine:alpha-1,3-D-mannoside beta-1, 4-N-acetylglucosaminyltransferase) and/or GnT-V (UDP-N-acetylglucosamine:alpha-1,6-D-mannoside beta-1, 6-N-acetylglucosaminyltransferase) into Chinese hamster ovary (CHO) cells producing human IFN-gamma. 10764830 6 89 theme GnT-V 866:870 arg1 activity 872:879 the GnT-V activity 862:879 the GnT-V activity 862:879 When the GnT-V activity was increased, triantennary sugar chains with a corresponding branch increased up to 55.7% of the total sugar chains. 10764830 4 90 theme sugar 688:692 arg1 chains 694:699 biantennary sugar chains 676:699 biantennary sugar chains 676:699 The parental CHO cells produced IFN-gamma with biantennary sugar chains mainly. 3956483 0 0 theme plasma 88:93 arg1 glycoproteins 57:69 mucus glycoproteins 51:69 mucus glycoproteins of human seminal plasma 51:93 Structure of neutral oligosaccharides derived from mucus glycoproteins of human seminal plasma. 3956483 0 1 theme seminal 80:86 arg1 plasma 88:93 human seminal plasma 74:93 human seminal plasma 74:93 Structure of neutral oligosaccharides derived from mucus glycoproteins of human seminal plasma. 3956483 1 2 theme methylation 346:356 arg1 analysis 358:365 methylation analysis 346:365 methylation analysis 346:365 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 3 from fraction 160:167 arg1 structures 108:117 The primary structures 96:117 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin 96:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 4 from alditols 144:151 arg1 fraction 160:167 the fraction 156:167 the fraction of neutral carbohydrates derived from human seminal plasma mucin 156:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 5 theme exoglycosidase 368:381 arg1 digestion 383:391 exoglycosidase digestion 368:391 exoglycosidase digestion 368:391 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 6 theme neutral 172:178 arg1 carbohydrates 180:192 neutral carbohydrates 172:192 neutral carbohydrates derived from human seminal plasma mucin 172:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 7 theme carbohydrates 180:192 arg1 fraction 160:167 the fraction 156:167 the fraction of neutral carbohydrates derived from human seminal plasma mucin 156:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 8 theme fast 272:275 arg1 bombardment 282:292 fast atom bombardment 272:292 fast atom bombardment 272:292 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 0 9 theme oligosaccharides 21:36 arg1 Structure 0:8 Structure 0:8 Structure of neutral oligosaccharides 0:36 Structure of neutral oligosaccharides derived from mucus glycoproteins of human seminal plasma. 3956483 1 10 theme atom 277:280 arg1 bombardment 282:292 fast atom bombardment 272:292 fast atom bombardment 272:292 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 11 theme primary 100:106 arg1 structures 108:117 The primary structures 96:117 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin 96:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 0 12 theme neutral 13:19 arg1 oligosaccharides 21:36 neutral oligosaccharides 13:36 neutral oligosaccharides 13:36 Structure of neutral oligosaccharides derived from mucus glycoproteins of human seminal plasma. 3956483 1 13 theme human 207:211 arg1 mucin 228:232 human seminal plasma mucin 207:232 human seminal plasma mucin 207:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 14 theme CrO3 398:401 arg1 oxidation 403:411 CrO3 oxidation 398:411 CrO3 oxidation 398:411 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 15 theme seminal 213:219 arg1 mucin 228:232 human seminal plasma mucin 207:232 human seminal plasma mucin 207:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 16 theme electron 298:305 arg1 spectrometry 319:330 electron impact mass spectrometry 298:330 electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation 298:411 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 17 attach derived 194:200 arg1 mucin 228:232 human seminal plasma mucin 207:232 human seminal plasma mucin 207:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 17 attach derived 194:200 arg2 carbohydrates 180:192 neutral carbohydrates 172:192 neutral carbohydrates derived from human seminal plasma mucin 172:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 18 theme plasma 221:226 arg1 mucin 228:232 human seminal plasma mucin 207:232 human seminal plasma mucin 207:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 19 theme impact 307:312 arg1 spectrometry 319:330 electron impact mass spectrometry 298:330 electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation 298:411 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 0 20 theme mucus 51:55 arg1 glycoproteins 57:69 mucus glycoproteins 51:69 mucus glycoproteins of human seminal plasma 51:93 Structure of neutral oligosaccharides derived from mucus glycoproteins of human seminal plasma. 3956483 1 21 theme mass 314:317 arg1 spectrometry 319:330 electron impact mass spectrometry 298:330 electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation 298:411 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 22 theme major 127:131 arg1 alditols 144:151 nine major saccharide alditols 122:151 nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin 122:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 23 from structures 108:117 arg1 fraction 160:167 the fraction 156:167 the fraction of neutral carbohydrates derived from human seminal plasma mucin 156:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 24 theme saccharide 133:142 arg1 alditols 144:151 nine major saccharide alditols 122:151 nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin 122:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 0 25 theme human 74:78 arg1 plasma 88:93 human seminal plasma 74:93 human seminal plasma 74:93 Structure of neutral oligosaccharides derived from mucus glycoproteins of human seminal plasma. 3956483 1 26 theme alditols 144:151 arg1 structures 108:117 The primary structures 96:117 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin 96:232 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 27 dep bombardment 282:292 arg1 the 259:261 the 259:261 the 259:261 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 1 27 dep bombardment 282:292 arg1 basis 263:267 basis 263:267 basis 263:267 The primary structures of nine major saccharide alditols in the fraction of neutral carbohydrates derived from human seminal plasma mucin have been established on the basis of fast atom bombardment and electron impact mass spectrometry combined with methylation analysis, exoglycosidase digestion, and CrO3 oxidation, as follows. 3956483 0 28 gly glycoproteins 57:69 arg1 glycoproteins 57:69 mucus glycoproteins 51:69 mucus glycoproteins of human seminal plasma 51:93 Structure of neutral oligosaccharides derived from mucus glycoproteins of human seminal plasma. 7496144 6 0 theme beta 1011:1014 arg1 1-->Asn 1016:1022 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn 956:1022 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn 956:1022 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 2 1 theme patients 314:321 arg1 one 303:305 one 303:305 one 303:305 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 1 theme patients 314:321 arg1 patients 314:321 the patients 310:321 the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) 310:389 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 6 2 theme following 929:937 arg1 structure 945:953 the following novel structure 925:953 the following novel structure 925:953 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 2 3 theme exchange 419:426 arg1 chromatography 428:441 anion exchange chromatography 413:441 anion exchange chromatography 413:441 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 5 4 theme nuclear 848:854 arg1 resonance 865:873 nuclear magnetic resonance 848:873 nuclear magnetic resonance (NMR) 848:879 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 5 4 theme nuclear 848:854 arg1 NMR 876:878 NMR 876:878 NMR 876:878 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 0 5 from Characterization 0:15 arg1 urine 81:85 the urine 77:85 the urine of a patient with aspartylglycosaminuria 77:126 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 7496144 2 6 from filtration 398:407 arg1 study 451:455 this study 446:455 this study 446:455 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 5 7 theme bombardment-mass 804:819 arg1 spectrometry 821:832 fast atom bombardment-mass spectrometry 794:832 fast atom bombardment-mass spectrometry (FAB-MS) 794:841 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 5 7 theme bombardment-mass 804:819 arg1 FAB-MS 835:840 FAB-MS 835:840 FAB-MS 835:840 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 0 8 theme patient 92:98 arg1 urine 81:85 the urine 77:85 the urine of a patient with aspartylglycosaminuria 77:126 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 7496144 5 9 theme magnetic 856:863 arg1 resonance 865:873 nuclear magnetic resonance 848:873 nuclear magnetic resonance (NMR) 848:879 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 5 9 theme magnetic 856:863 arg1 NMR 876:878 NMR 876:878 NMR 876:878 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 2 10 dep AG-4 385:388 arg1 to 382:383 to 382:383 to 382:383 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 6 11 theme alpha 979:983 arg1 beta 1011:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 956:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn 956:1022 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 1 12 theme first 160:164 arg1 patients 184:191 the first time two Japanese patients 156:191 the first time two Japanese patients with aspartylglycosaminuria (AGU) 156:225 We previously reported for the first time two Japanese patients with aspartylglycosaminuria (AGU). 7496144 0 13 theme novel 41:45 arg1 N-glycosides 59:70 a novel disialo Asn N-glycosides 39:70 a novel disialo Asn N-glycosides 39:70 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 7496144 0 14 with patient 92:98 arg1 aspartylglycosaminuria 105:126 aspartylglycosaminuria 105:126 aspartylglycosaminuria 105:126 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 7496144 3 15 theme AG-5 480:483 arg1 purification 464:475 Final purification 458:475 Final purification of AG-5 458:483 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 1 16 theme time 166:169 arg1 patients 184:191 the first time two Japanese patients 156:191 the first time two Japanese patients with aspartylglycosaminuria (AGU) 156:225 We previously reported for the first time two Japanese patients with aspartylglycosaminuria (AGU). 7496144 6 17 theme alpha 962:966 arg1 beta 1011:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 956:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn 956:1022 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 3 18 theme electrochemical 504:518 arg1 chromatography 568:581 high performance liquid chromatography 544:581 high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD) 544:626 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 18 theme electrochemical 504:518 arg1 method 536:541 an electrochemical chromatographic method 501:541 an electrochemical chromatographic method 501:541 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 6 19 theme 1-->4GlcNAc 999:1009 arg1 beta 1011:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 956:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn 956:1022 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 3 20 theme chromatographic 520:534 arg1 chromatography 568:581 high performance liquid chromatography 544:581 high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD) 544:626 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 20 theme chromatographic 520:534 arg1 method 536:541 an electrochemical chromatographic method 501:541 an electrochemical chromatographic method 501:541 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 1 21 theme Japanese 175:182 arg1 patients 184:191 the first time two Japanese patients 156:191 the first time two Japanese patients with aspartylglycosaminuria (AGU) 156:225 We previously reported for the first time two Japanese patients with aspartylglycosaminuria (AGU). 7496144 0 22 theme monosialo 25:33 arg1 Characterization 0:15 Characterization 0:15 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 0:127 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 7496144 3 23 theme liquid 561:566 arg1 chromatography 568:581 high performance liquid chromatography 544:581 high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD) 544:626 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 23 theme liquid 561:566 arg1 method 536:541 an electrochemical chromatographic method 501:541 an electrochemical chromatographic method 501:541 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 24 theme high 544:547 arg1 chromatography 568:581 high performance liquid chromatography 544:581 high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD) 544:626 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 24 theme high 544:547 arg1 method 536:541 an electrochemical chromatographic method 501:541 an electrochemical chromatographic method 501:541 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 2 25 theme AG-1 377:380 arg1 N-glycosides 363:374 four known monosialo Asn N-glycosides 338:374 four known monosialo Asn N-glycosides (AG-1 to AG-4) 338:389 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 25 theme AG-1 377:380 arg1 AG-4 385:388 AG-1 to AG-4 377:388 AG-1 to AG-4 377:388 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 5 26 theme permethylation 772:785 arg1 study 787:791 a permethylation study 770:791 a permethylation study 770:791 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 6 27 theme structural 895:904 arg1 analysis 906:913 the structural analysis 891:913 the structural analysis 891:913 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 2 28 from chromatography 428:441 arg1 study 451:455 this study 446:455 this study 446:455 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 4 29 theme AG-5 642:645 arg1 urine 674:678 approximately 1 mg l-1 urine 651:678 approximately 1 mg l-1 urine 651:678 The yield of AG-5 was approximately 1 mg l-1 urine. 7496144 4 29 theme AG-5 642:645 arg1 yield 633:637 The yield 629:637 The yield of AG-5 629:645 The yield of AG-5 was approximately 1 mg l-1 urine. 7496144 2 30 theme anion 413:417 arg1 chromatography 428:441 anion exchange chromatography 413:441 anion exchange chromatography 413:441 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 31 attach isolated 276:283 arg2 N-glycoside 248:258 A novel disialo Asn N-glycoside 228:258 A novel disialo Asn N-glycoside (AG-5) 228:265 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 31 attach isolated 276:283 arg1 urine 294:298 the urine 290:298 the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) 290:389 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 31 attach isolated 276:283 arg2 AG-5 261:264 AG-5 261:264 AG-5 261:264 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 1 32 with patients 184:191 arg1 AGU 222:224 AGU 222:224 AGU 222:224 We previously reported for the first time two Japanese patients with aspartylglycosaminuria (AGU). 7496144 1 32 with patients 184:191 arg1 aspartylglycosaminuria 198:219 aspartylglycosaminuria 198:219 aspartylglycosaminuria (AGU) 198:225 We previously reported for the first time two Japanese patients with aspartylglycosaminuria (AGU). 7496144 6 33 theme 2-->8NeuAc 968:977 arg1 beta 1011:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 956:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn 956:1022 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 2 34 dep N-glycosides 363:374 arg1 addition 326:333 addition 326:333 addition 326:333 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 6 35 theme beta 994:997 arg1 beta 1011:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 956:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn 956:1022 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 5 36 theme fast 794:797 arg1 spectrometry 821:832 fast atom bombardment-mass spectrometry 794:832 fast atom bombardment-mass spectrometry (FAB-MS) 794:841 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 5 36 theme fast 794:797 arg1 FAB-MS 835:840 FAB-MS 835:840 FAB-MS 835:840 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 2 37 theme monosialo 349:357 arg1 N-glycosides 363:374 four known monosialo Asn N-glycosides 338:374 four known monosialo Asn N-glycosides (AG-1 to AG-4) 338:389 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 37 theme monosialo 349:357 arg1 AG-4 385:388 AG-1 to AG-4 377:388 AG-1 to AG-4 377:388 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 3 38 theme pulsed 588:593 arg1 HPLC-PAD 618:625 HPLC-PAD 618:625 HPLC-PAD 618:625 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 38 theme pulsed 588:593 arg1 detector 608:615 pulsed amperometric detector 588:615 pulsed amperometric detector (HPLC-PAD) 588:626 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 39 theme amperometric 595:606 arg1 HPLC-PAD 618:625 HPLC-PAD 618:625 HPLC-PAD 618:625 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 39 theme amperometric 595:606 arg1 detector 608:615 pulsed amperometric detector 588:615 pulsed amperometric detector (HPLC-PAD) 588:626 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 40 theme performance 549:559 arg1 chromatography 568:581 high performance liquid chromatography 544:581 high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD) 544:626 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 40 theme performance 549:559 arg1 method 536:541 an electrochemical chromatographic method 501:541 an electrochemical chromatographic method 501:541 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 5 41 theme atom 799:802 arg1 spectrometry 821:832 fast atom bombardment-mass spectrometry 794:832 fast atom bombardment-mass spectrometry (FAB-MS) 794:841 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 5 41 theme atom 799:802 arg1 FAB-MS 835:840 FAB-MS 835:840 FAB-MS 835:840 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 2 42 theme Asn 359:361 arg1 N-glycosides 363:374 four known monosialo Asn N-glycosides 338:374 four known monosialo Asn N-glycosides (AG-1 to AG-4) 338:389 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 42 theme Asn 359:361 arg1 AG-4 385:388 AG-1 to AG-4 377:388 AG-1 to AG-4 377:388 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 0 43 theme disialo 47:53 arg1 N-glycosides 59:70 a novel disialo Asn N-glycosides 39:70 a novel disialo Asn N-glycosides 39:70 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 7496144 5 44 theme gas-liquid 743:752 arg1 chromatography 754:767 gas-liquid chromatography 743:767 gas-liquid chromatography 743:767 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 3 45 with chromatography 568:581 arg1 HPLC-PAD 618:625 HPLC-PAD 618:625 HPLC-PAD 618:625 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 3 45 with chromatography 568:581 arg1 detector 608:615 pulsed amperometric detector 588:615 pulsed amperometric detector (HPLC-PAD) 588:626 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 6 46 contain had 921:923 arg1 AG-5 916:919 AG-5 916:919 AG-5 916:919 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 6 46 contain had 921:923 arg2 structure 945:953 the following novel structure 925:953 the following novel structure 925:953 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 4 47 theme mg 667:668 arg1 yield 633:637 The yield 629:637 The yield of AG-5 629:645 The yield of AG-5 was approximately 1 mg l-1 urine. 7496144 4 47 theme mg 667:668 arg1 urine 674:678 approximately 1 mg l-1 urine 651:678 approximately 1 mg l-1 urine 651:678 The yield of AG-5 was approximately 1 mg l-1 urine. 7496144 2 48 theme gel 394:396 arg1 filtration 398:407 gel filtration 394:407 gel filtration 394:407 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 49 theme one 303:305 arg1 urine 294:298 the urine 290:298 the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) 290:389 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 5 50 theme AG-1 708:711 arg1 structures 694:703 The chemical structures 681:703 The chemical structures of AG-1 to AG-5 681:719 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 5 51 theme chemical 685:692 arg1 structures 694:703 The chemical structures 681:703 The chemical structures of AG-1 to AG-5 681:719 The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). 7496144 2 52 theme Asn 244:246 arg1 AG-5 261:264 AG-5 261:264 AG-5 261:264 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 52 theme Asn 244:246 arg1 N-glycoside 248:258 A novel disialo Asn N-glycoside 228:258 A novel disialo Asn N-glycoside (AG-5) 228:265 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 4 53 theme l-1 670:672 arg1 yield 633:637 The yield 629:637 The yield of AG-5 629:645 The yield of AG-5 was approximately 1 mg l-1 urine. 7496144 4 53 theme l-1 670:672 arg1 urine 674:678 approximately 1 mg l-1 urine 651:678 approximately 1 mg l-1 urine 651:678 The yield of AG-5 was approximately 1 mg l-1 urine. 7496144 0 54 theme N-glycosides 59:70 arg1 Characterization 0:15 Characterization 0:15 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 0:127 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 7496144 0 55 from urine 81:85 arg1 Characterization 0:15 Characterization 0:15 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 0:127 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 7496144 0 55 from urine 81:85 arg1 monosialo 25:33 monosialo 25:33 monosialo 25:33 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 7496144 2 56 theme disialo 236:242 arg1 AG-5 261:264 AG-5 261:264 AG-5 261:264 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 56 theme disialo 236:242 arg1 N-glycoside 248:258 A novel disialo Asn N-glycoside 228:258 A novel disialo Asn N-glycoside (AG-5) 228:265 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 6 57 theme 2-->3Gal 985:992 arg1 beta 1011:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 956:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn 956:1022 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 3 58 theme Final 458:462 arg1 purification 464:475 Final purification 458:475 Final purification of AG-5 458:483 Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). 7496144 2 59 theme known 343:347 arg1 N-glycosides 363:374 four known monosialo Asn N-glycosides 338:374 four known monosialo Asn N-glycosides (AG-1 to AG-4) 338:389 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 59 theme known 343:347 arg1 AG-4 385:388 AG-1 to AG-4 377:388 AG-1 to AG-4 377:388 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 0 60 theme Asn 55:57 arg1 N-glycosides 59:70 a novel disialo Asn N-glycosides 39:70 a novel disialo Asn N-glycosides 39:70 Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria. 7496144 2 61 theme novel 230:234 arg1 AG-5 261:264 AG-5 261:264 AG-5 261:264 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 2 61 theme novel 230:234 arg1 N-glycoside 248:258 A novel disialo Asn N-glycoside 228:258 A novel disialo Asn N-glycoside (AG-5) 228:265 A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. 7496144 6 62 theme NeuAc 956:960 arg1 beta 1011:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 956:1014 NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn 956:1022 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 7496144 6 63 theme novel 939:943 arg1 structure 945:953 the following novel structure 925:953 the following novel structure 925:953 Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn. 11445551 7 0 from context 1186:1192 arg1 investigations 1124:1137 investigations 1124:1137 investigations of mucin posttranslational modification in the context of disease 1124:1203 Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease. 11445551 7 1 theme modification 1166:1177 arg1 investigations 1124:1137 investigations 1124:1137 investigations of mucin posttranslational modification in the context of disease 1124:1203 Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease. 11445551 3 2 theme MUC1 580:583 arg1 MUC1F 594:598 MUC1F 594:598 MUC1F 594:598 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 3 2 theme MUC1 580:583 arg1 protein 585:591 epitope-tagged MUC1 protein 565:591 epitope-tagged MUC1 protein (MUC1F) 565:599 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 1 3 theme serine- 155:161 arg1 domains 201:207 serine- and threonine-rich tandem repeat (TR) domains 155:207 serine- and threonine-rich tandem repeat (TR) domains 155:207 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 4 4 with association 678:688 arg1 surface 704:710 the cell surface 695:710 the cell surface 695:710 These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. 11445551 2 5 theme secreted 348:355 arg1 mucins 357:362 the cell surface-associated and secreted mucins 316:362 the cell surface-associated and secreted mucins 316:362 In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. 11445551 3 6 from MUC5B 513:517 arg1 sequences 475:483 TR sequences 472:483 TR sequences from MUC2, MUC4, MUC5AC, or MUC5B 472:517 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 6 7 with reactivity 971:980 arg1 antibodies 987:996 antibodies 987:996 antibodies against particular blood-group and tumor-associated carbohydrate antigens 987:1070 Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. 11445551 7 8 theme mucin 1142:1146 arg1 modification 1166:1177 mucin posttranslational modification 1142:1177 mucin posttranslational modification in the context of disease 1142:1203 Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease. 11445551 3 9 from MUC4 496:499 arg1 sequences 475:483 TR sequences 472:483 TR sequences from MUC2, MUC4, MUC5AC, or MUC5B 472:517 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 4 10 theme culture 729:735 arg1 media 737:741 culture media 729:741 culture media 729:741 These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. 11445551 5 11 theme domains 773:779 arg1 presence 748:755 The presence 744:755 The presence of different TR domains within the chimeric mucins 744:806 The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. 11445551 1 12 theme biochemical 51:61 arg1 properties 79:88 The biochemical and biophysical properties 47:88 The biochemical and biophysical properties of mucins 47:98 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 2 13 theme mucins 357:362 arg1 properties 302:311 the properties 298:311 the properties of the cell surface-associated and secreted mucins 298:362 In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. 11445551 6 14 theme particular 1006:1015 arg1 blood-group 1017:1027 particular blood-group 1006:1027 particular blood-group 1006:1027 Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. 11445551 3 15 from MUC5AC 502:507 arg1 sequences 475:483 TR sequences 472:483 TR sequences from MUC2, MUC4, MUC5AC, or MUC5B 472:517 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 3 16 theme domains 417:423 arg1 O-glycosylation 389:403 the O-glycosylation 385:403 the O-glycosylation of mucin TR domains 385:423 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 1 17 theme threonine-rich 167:180 arg1 domains 201:207 serine- and threonine-rich tandem repeat (TR) domains 155:207 serine- and threonine-rich tandem repeat (TR) domains 155:207 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 5 18 theme different 760:768 arg1 domains 773:779 different TR domains 760:779 different TR domains 760:779 The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. 11445551 3 19 theme mucin 408:412 arg1 domains 417:423 mucin TR domains 408:423 mucin TR domains 408:423 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 1 20 theme biophysical 67:77 arg1 properties 79:88 The biochemical and biophysical properties 47:88 The biochemical and biophysical properties of mucins 47:98 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 1 21 theme tandem 182:187 arg1 repeat 189:194 tandem repeat 182:194 serine- and threonine-rich tandem repeat (TR) domains 155:207 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 1 21 theme tandem 182:187 arg1 TR 197:198 TR 197:198 TR 197:198 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 5 22 theme TR 770:771 arg1 domains 773:779 different TR domains 760:779 different TR domains 760:779 The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. 11445551 6 23 theme bombardment 937:947 arg1 spectrometry 954:965 fast atom bombardment mass spectrometry 927:965 fast atom bombardment mass spectrometry 927:965 Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. 11445551 7 24 theme Future 1073:1078 arg1 applications 1080:1091 Future applications 1073:1091 Future applications of these chimeras 1073:1109 Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease. 11445551 1 25 theme repeat 189:194 arg1 domains 201:207 serine- and threonine-rich tandem repeat (TR) domains 155:207 serine- and threonine-rich tandem repeat (TR) domains 155:207 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 0 26 theme In 0:1 arg1 glycosylation 8:20 In vivo glycosylation 0:20 In vivo glycosylation of mucin tandem repeats 0:44 In vivo glycosylation of mucin tandem repeats. 11445551 7 27 theme disease 1197:1203 arg1 context 1186:1192 the context 1182:1192 the context of disease 1182:1203 Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease. 11445551 2 28 gly O-glycosylation 249:263 arg1 number 215:220 a number 213:220 a number of human diseases 213:238 In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. 11445551 3 29 theme epitope-tagged 565:578 arg1 MUC1F 594:598 MUC1F 594:598 MUC1F 594:598 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 3 29 theme epitope-tagged 565:578 arg1 protein 585:591 epitope-tagged MUC1 protein 565:591 epitope-tagged MUC1 protein (MUC1F) 565:599 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 7 30 theme posttranslational 1148:1164 arg1 modification 1166:1177 mucin posttranslational modification 1142:1177 mucin posttranslational modification in the context of disease 1142:1203 Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease. 11445551 3 31 from MUC2 490:493 arg1 sequences 475:483 TR sequences 472:483 TR sequences from MUC2, MUC4, MUC5AC, or MUC5B 472:517 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 1 32 theme mucins 93:98 arg1 properties 79:88 The biochemical and biophysical properties 47:88 The biochemical and biophysical properties of mucins 47:98 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 5 33 theme chimeric 792:799 arg1 mucins 801:806 the chimeric mucins 788:806 the chimeric mucins 788:806 The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. 11445551 4 34 theme cell 699:702 arg1 surface 704:710 the cell surface 695:710 the cell surface 695:710 These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. 11445551 6 35 theme mass 949:952 arg1 spectrometry 954:965 fast atom bombardment mass spectrometry 927:965 fast atom bombardment mass spectrometry 927:965 Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. 11445551 7 36 theme chimeras 1102:1109 arg1 applications 1080:1091 Future applications 1073:1091 Future applications of these chimeras 1073:1109 Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease. 11445551 7 37 from modification 1166:1177 arg1 context 1186:1192 the context 1182:1192 the context of disease 1182:1203 Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease. 11445551 5 38 theme limited 824:830 arg1 influence 832:840 limited influence 824:840 limited influence 824:840 The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. 11445551 0 39 theme tandem 31:36 arg1 repeats 38:44 mucin tandem repeats 25:44 mucin tandem repeats 25:44 In vivo glycosylation of mucin tandem repeats. 11445551 4 40 theme expected 669:676 arg1 association 678:688 the expected association 665:688 the expected association with the cell surface 665:710 These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. 11445551 3 41 with mucins 460:465 arg1 sequences 475:483 TR sequences 472:483 TR sequences from MUC2, MUC4, MUC5AC, or MUC5B 472:517 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 3 42 theme recombinant 439:449 arg1 mucins 460:465 recombinant chimeric mucins 439:465 recombinant chimeric mucins 439:465 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 1 43 theme domains 201:207 arg1 O-glycosylation 136:150 extensive O-glycosylation 126:150 extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains 126:207 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 0 44 theme mucin 25:29 arg1 repeats 38:44 mucin tandem repeats 25:44 mucin tandem repeats 25:44 In vivo glycosylation of mucin tandem repeats. 11445551 4 45 with release 716:722 arg1 surface 704:710 the cell surface 695:710 the cell surface 695:710 These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. 11445551 3 46 theme TR 414:415 arg1 domains 417:423 mucin TR domains 408:423 mucin TR domains 408:423 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 3 47 theme chimeric 451:458 arg1 mucins 460:465 recombinant chimeric mucins 439:465 recombinant chimeric mucins 439:465 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 7 48 from investigations 1124:1137 arg1 context 1186:1192 the context 1182:1192 the context of disease 1182:1203 Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease. 11445551 6 49 theme atom 932:935 arg1 spectrometry 954:965 fast atom bombardment mass spectrometry 927:965 fast atom bombardment mass spectrometry 927:965 Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. 11445551 4 50 gly O-glycosylated 639:652 arg1 mucins 615:620 These hybrid mucins 602:620 These hybrid mucins 602:620 These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. 11445551 6 51 from Alterations 881:891 arg1 glycosylation 896:908 glycosylation 896:908 glycosylation 896:908 Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. 11445551 0 52 gly glycosylation 8:20 arg1 repeats 38:44 mucin tandem repeats 25:44 mucin tandem repeats 25:44 In vivo glycosylation of mucin tandem repeats. 11445551 0 53 theme repeats 38:44 arg1 glycosylation 8:20 In vivo glycosylation 0:20 In vivo glycosylation of mucin tandem repeats 0:44 In vivo glycosylation of mucin tandem repeats. 11445551 3 54 gly O-glycosylation 389:403 arg1 domains 417:423 mucin TR domains 408:423 mucin TR domains 408:423 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 1 55 gly O-glycosylation 136:150 arg1 domains 201:207 serine- and threonine-rich tandem repeat (TR) domains 155:207 serine- and threonine-rich tandem repeat (TR) domains 155:207 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 3 56 theme native 551:556 arg1 TRs 558:560 the native TRs 547:560 the native TRs of epitope-tagged MUC1 protein (MUC1F) 547:599 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 2 57 theme surface-associated 325:342 arg1 mucins 357:362 the cell surface-associated and secreted mucins 316:362 the cell surface-associated and secreted mucins 316:362 In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. 11445551 2 58 theme human 225:229 arg1 diseases 231:238 human diseases 225:238 human diseases 225:238 In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. 11445551 3 59 theme protein 585:591 arg1 TRs 558:560 the native TRs 547:560 the native TRs of epitope-tagged MUC1 protein (MUC1F) 547:599 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 2 60 theme cell 320:323 arg1 mucins 357:362 the cell surface-associated and secreted mucins 316:362 the cell surface-associated and secreted mucins 316:362 In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. 11445551 6 61 theme tumor-associated 1033:1048 arg1 antigens 1063:1070 tumor-associated carbohydrate antigens 1033:1070 tumor-associated carbohydrate antigens 1033:1070 Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. 11445551 6 62 with spectrometry 954:965 arg1 antibodies 987:996 antibodies 987:996 antibodies against particular blood-group and tumor-associated carbohydrate antigens 987:1070 Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. 11445551 2 63 theme aberrant 240:247 arg1 O-glycosylation 249:263 aberrant O-glycosylation 240:263 aberrant O-glycosylation 240:263 In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. 11445551 1 64 theme extensive 126:134 arg1 O-glycosylation 136:150 extensive O-glycosylation 126:150 extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains 126:207 The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. 11445551 2 65 from variations 284:293 arg1 properties 302:311 the properties 298:311 the properties of the cell surface-associated and secreted mucins 298:362 In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. 11445551 3 66 theme TR 472:473 arg1 sequences 475:483 TR sequences 472:483 TR sequences from MUC2, MUC4, MUC5AC, or MUC5B 472:517 To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). 11445551 6 67 theme carbohydrate 1050:1061 arg1 antigens 1063:1070 tumor-associated carbohydrate antigens 1033:1070 tumor-associated carbohydrate antigens 1033:1070 Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. 11445551 2 68 theme diseases 231:238 arg1 number 215:220 a number 213:220 a number of human diseases 213:238 In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. 11445551 4 69 theme hybrid 608:613 arg1 mucins 615:620 These hybrid mucins 602:620 These hybrid mucins 602:620 These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. 11445551 5 70 contain have 819:822 arg2 influence 832:840 limited influence 824:840 limited influence 824:840 The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. 11445551 5 70 contain have 819:822 arg1 presence 748:755 The presence 744:755 The presence of different TR domains within the chimeric mucins 744:806 The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. 11445551 0 71 dep In 0:1 arg1 vivo 3:6 vivo 3:6 vivo 3:6 In vivo glycosylation of mucin tandem repeats. 11445551 5 72 theme posttranslational 851:867 arg1 processing 869:878 their posttranslational processing 845:878 their posttranslational processing 845:878 The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. 11445551 6 73 theme fast 927:930 arg1 spectrometry 954:965 fast atom bombardment mass spectrometry 927:965 fast atom bombardment mass spectrometry 927:965 Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. 6487655 1 0 from complement 342:351 arg1 silica 388:393 octadecyl silica 378:393 octadecyl silica 378:393 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 4 1 theme carbohydrate 962:973 arg1 content 975:981 essentially the entire carbohydrate content 939:981 essentially the entire carbohydrate content 939:981 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 3 2 theme retention 724:732 arg1 times 734:738 relative retention times 715:738 relative retention times ranging from 3 to 12 715:759 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 0 3 from mucins 180:185 arg1 isolation 103:111 isolation 103:111 isolation 103:111 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 0 3 from mucins 180:185 arg1 characterization 117:132 characterization 117:132 characterization 117:132 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 1 4 theme octadecyl 378:386 arg1 silica 388:393 octadecyl silica 378:393 octadecyl silica 378:393 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 1 5 theme mucin 493:497 arg1 glycoproteins 499:511 mucin glycoproteins 493:511 mucin glycoproteins 493:511 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 2 6 theme size 576:579 arg1 basis 557:561 the basis 553:561 the basis of molecular size 553:579 The former technique separates well on the basis of molecular size, while the latter method shows selectivity for stereoisomers. 6487655 3 7 theme excellent 775:783 arg1 separations 797:807 excellent preparative separations 775:807 excellent preparative separations in reverse-phase chromatography 775:839 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 1 8 theme glycoproteins 499:511 arg1 degradation 478:488 alkaline borohydride degradation 457:488 alkaline borohydride degradation of mucin glycoproteins 457:511 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 2 9 theme molecular 566:574 arg1 size 576:579 molecular size 566:579 molecular size 566:579 The former technique separates well on the basis of molecular size, while the latter method shows selectivity for stereoisomers. 6487655 3 10 theme preparative 785:795 arg1 separations 797:807 excellent preparative separations 775:807 excellent preparative separations in reverse-phase chromatography 775:839 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 3 11 from separations 797:807 arg1 chromatography 826:839 reverse-phase chromatography 812:839 reverse-phase chromatography 812:839 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 0 12 dep isolation 103:111 arg1 the 99:101 the 99:101 the 99:101 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 1 13 theme Normal-phase 188:199 arg1 HPLC 238:241 HPLC 238:241 HPLC 238:241 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 1 13 theme Normal-phase 188:199 arg1 chromatography 222:235 Normal-phase high-pressure liquid chromatography 188:235 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile 188:302 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 1 13 theme Normal-phase 188:199 arg1 complement 342:351 an especially suitable complement 319:351 an especially suitable complement to reverse-phase HPLC on octadecyl silica 319:393 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 7 14 theme oligosaccharides 1288:1303 arg1 Structures 1274:1283 Structures 1274:1283 Structures of oligosaccharides differing by only one or two residues from those whose NMR spectra are known 1274:1380 Structures of oligosaccharides differing by only one or two residues from those whose NMR spectra are known may be deduced by a simple algorithm utilizing chemical shift analogies. 6487655 6 15 attach isolated 1137:1144 arg2 oligosaccharides 1104:1119 those oligosaccharides 1098:1119 those oligosaccharides which have been isolated from other sources and whose NMR spectra have been previously reported 1098:1215 For those oligosaccharides which have been isolated from other sources and whose NMR spectra have been previously reported, unambiguous structural identification follows directly. 6487655 6 15 attach isolated 1137:1144 arg1 sources 1157:1163 other sources 1151:1163 other sources 1151:1163 For those oligosaccharides which have been isolated from other sources and whose NMR spectra have been previously reported, unambiguous structural identification follows directly. 6487655 4 16 theme active 897:902 arg1 b 895:895 Lewis b active 889:902 Lewis b active 889:902 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 4 17 attach isolated 994:1001 arg1 glycoprotein 869:880 a single ovarian cyst glycoprotein 847:880 a single ovarian cyst glycoprotein 847:880 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 4 17 attach isolated 994:1001 arg2 oligosaccharides 908:923 13 oligosaccharides 905:923 13 oligosaccharides 905:923 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 4 17 attach isolated 994:1001 arg1 H 883:883 H 883:883 H 883:883 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 4 17 attach isolated 994:1001 arg1 b 895:895 Lewis b active 889:902 Lewis b active 889:902 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 1 18 theme high-pressure 201:213 arg1 HPLC 238:241 HPLC 238:241 HPLC 238:241 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 1 18 theme high-pressure 201:213 arg1 chromatography 222:235 Normal-phase high-pressure liquid chromatography 188:235 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile 188:302 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 1 18 theme high-pressure 201:213 arg1 complement 342:351 an especially suitable complement 319:351 an especially suitable complement to reverse-phase HPLC on octadecyl silica 319:393 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 4 19 gly glycoprotein 869:880 arg1 glycoprotein 869:880 a single ovarian cyst glycoprotein 847:880 a single ovarian cyst glycoprotein 847:880 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 1 20 with chromatography 222:235 arg1 elution 272:278 elution 272:278 elution by aqueous acetonitrile 272:302 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 1 21 theme liquid 215:220 arg1 HPLC 238:241 HPLC 238:241 HPLC 238:241 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 1 21 theme liquid 215:220 arg1 chromatography 222:235 Normal-phase high-pressure liquid chromatography 188:235 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile 188:302 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 1 21 theme liquid 215:220 arg1 complement 342:351 an especially suitable complement 319:351 an especially suitable complement to reverse-phase HPLC on octadecyl silica 319:393 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 3 22 theme reverse-phase 812:824 arg1 chromatography 826:839 reverse-phase chromatography 812:839 reverse-phase chromatography 812:839 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 6 23 theme structural 1230:1239 arg1 identification 1241:1254 unambiguous structural identification 1218:1254 unambiguous structural identification 1218:1254 For those oligosaccharides which have been isolated from other sources and whose NMR spectra have been previously reported, unambiguous structural identification follows directly. 6487655 3 24 theme relative 715:722 arg1 times 734:738 relative retention times 715:738 relative retention times ranging from 3 to 12 715:759 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 0 25 theme normal-phase 19:30 arg1 combination 4:14 The combination 0:14 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 0:186 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 7 26 theme chemical 1429:1436 arg1 analogies 1444:1452 chemical shift analogies 1429:1452 chemical shift analogies 1429:1452 Structures of oligosaccharides differing by only one or two residues from those whose NMR spectra are known may be deduced by a simple algorithm utilizing chemical shift analogies. 6487655 0 27 theme oligosaccharide 137:151 arg1 alditols 153:160 oligosaccharide alditols 137:160 oligosaccharide alditols 137:160 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 4 28 theme Lewis 889:893 arg1 b 895:895 Lewis b active 889:902 Lewis b active 889:902 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 1 29 theme aqueous 283:289 arg1 acetonitrile 291:302 aqueous acetonitrile 283:302 aqueous acetonitrile 283:302 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 3 30 dep tetra- 667:672 arg1 alditols 701:708 alditols 701:708 alditols 701:708 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 3 31 dep 12 758:759 arg1 to 755:756 to 755:756 to 755:756 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 2 32 theme latter 592:597 arg1 method 599:604 the latter method 588:604 the latter method 588:604 The former technique separates well on the basis of molecular size, while the latter method shows selectivity for stereoisomers. 6487655 5 33 theme 12 1022:1023 arg1 structures 1008:1017 The structures 1004:1017 The structures of 12 of the oligosaccharides 1004:1047 The structures of 12 of the oligosaccharides have been determined by 1H-NMR spectroscopy. 6487655 2 34 theme former 518:523 arg1 technique 525:533 The former technique 514:533 The former technique 514:533 The former technique separates well on the basis of molecular size, while the latter method shows selectivity for stereoisomers. 6487655 0 35 theme reverse-phase 36:48 arg1 chromatography 71:84 reverse-phase high-pressure liquid chromatography 36:84 reverse-phase high-pressure liquid chromatography 36:84 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 1 36 theme oligosaccharide 420:434 arg1 alditols 436:443 oligosaccharide alditols 420:443 oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins 420:511 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 7 37 theme simple 1402:1407 arg1 algorithm 1409:1417 a simple algorithm 1400:1417 a simple algorithm utilizing chemical shift analogies 1400:1452 Structures of oligosaccharides differing by only one or two residues from those whose NMR spectra are known may be deduced by a simple algorithm utilizing chemical shift analogies. 6487655 0 38 theme alditols 153:160 arg1 isolation 103:111 isolation 103:111 isolation 103:111 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 0 38 theme alditols 153:160 arg1 characterization 117:132 characterization 117:132 characterization 117:132 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 1 39 theme alditols 436:443 arg1 fractionation 403:415 the fractionation 399:415 the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins 399:511 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 0 40 theme liquid 64:69 arg1 chromatography 71:84 reverse-phase high-pressure liquid chromatography 36:84 reverse-phase high-pressure liquid chromatography 36:84 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 1 41 theme suitable 333:340 arg1 chromatography 222:235 Normal-phase high-pressure liquid chromatography 188:235 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile 188:302 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 1 41 theme suitable 333:340 arg1 complement 342:351 an especially suitable complement 319:351 an especially suitable complement to reverse-phase HPLC on octadecyl silica 319:393 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 0 42 theme cyst 175:178 arg1 mucins 180:185 ovarian cyst mucins 167:185 ovarian cyst mucins 167:185 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 0 43 theme high-pressure 50:62 arg1 chromatography 71:84 reverse-phase high-pressure liquid chromatography 36:84 reverse-phase high-pressure liquid chromatography 36:84 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 0 44 theme ovarian 167:173 arg1 mucins 180:185 ovarian cyst mucins 167:185 ovarian cyst mucins 167:185 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 3 45 theme Stereoisomeric 643:656 arg1 pairs 658:662 Stereoisomeric pairs 643:662 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols 643:708 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 0 46 with combination 4:14 arg1 NMR 91:93 NMR 91:93 NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins 91:185 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 3 47 theme hexasaccharide 686:699 arg1 pairs 658:662 Stereoisomeric pairs 643:662 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols 643:708 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 7 48 theme shift 1438:1442 arg1 analogies 1444:1452 chemical shift analogies 1429:1452 chemical shift analogies 1429:1452 Structures of oligosaccharides differing by only one or two residues from those whose NMR spectra are known may be deduced by a simple algorithm utilizing chemical shift analogies. 6487655 1 49 theme alkaline 457:464 arg1 borohydride 466:476 alkaline borohydride 457:476 alkaline borohydride degradation of mucin glycoproteins 457:511 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 3 50 theme penta- 675:680 arg1 pairs 658:662 Stereoisomeric pairs 643:662 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols 643:708 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 7 51 theme NMR 1360:1362 arg1 spectra 1364:1370 spectra 1364:1370 spectra 1364:1370 Structures of oligosaccharides differing by only one or two residues from those whose NMR spectra are known may be deduced by a simple algorithm utilizing chemical shift analogies. 6487655 6 52 theme unambiguous 1218:1228 arg1 identification 1241:1254 unambiguous structural identification 1218:1254 unambiguous structural identification 1218:1254 For those oligosaccharides which have been isolated from other sources and whose NMR spectra have been previously reported, unambiguous structural identification follows directly. 6487655 1 53 theme amino-bonded 247:258 arg1 silica 260:265 amino-bonded silica 247:265 amino-bonded silica 247:265 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 4 54 theme single 849:854 arg1 glycoprotein 869:880 a single ovarian cyst glycoprotein 847:880 a single ovarian cyst glycoprotein 847:880 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 1 55 theme borohydride 466:476 arg1 degradation 478:488 alkaline borohydride degradation 457:488 alkaline borohydride degradation of mucin glycoproteins 457:511 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 4 56 theme ovarian 856:862 arg1 glycoprotein 869:880 a single ovarian cyst glycoprotein 847:880 a single ovarian cyst glycoprotein 847:880 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 4 57 theme cyst 864:867 arg1 glycoprotein 869:880 a single ovarian cyst glycoprotein 847:880 a single ovarian cyst glycoprotein 847:880 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 5 58 theme oligosaccharides 1032:1047 arg1 12 1022:1023 12 1022:1023 12 1022:1023 The structures of 12 of the oligosaccharides have been determined by 1H-NMR spectroscopy. 6487655 5 58 theme oligosaccharides 1032:1047 arg1 oligosaccharides 1032:1047 the oligosaccharides 1028:1047 the oligosaccharides 1028:1047 The structures of 12 of the oligosaccharides have been determined by 1H-NMR spectroscopy. 6487655 3 59 theme tetra- 667:672 arg1 pairs 658:662 Stereoisomeric pairs 643:662 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols 643:708 Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. 6487655 1 60 from chromatography 222:235 arg1 silica 260:265 amino-bonded silica 247:265 amino-bonded silica 247:265 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 4 61 theme entire 955:960 arg1 content 975:981 essentially the entire carbohydrate content 939:981 essentially the entire carbohydrate content 939:981 From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. 6487655 6 62 theme other 1151:1155 arg1 sources 1157:1163 other sources 1151:1163 other sources 1151:1163 For those oligosaccharides which have been isolated from other sources and whose NMR spectra have been previously reported, unambiguous structural identification follows directly. 6487655 0 63 theme chromatography 71:84 arg1 combination 4:14 The combination 0:14 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 0:186 The combination of normal-phase and reverse-phase high-pressure liquid chromatography with NMR for the isolation and characterization of oligosaccharide alditols from ovarian cyst mucins. 6487655 1 64 theme reverse-phase 356:368 arg1 HPLC 370:373 reverse-phase HPLC 356:373 reverse-phase HPLC 356:373 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 6487655 5 65 theme 1H-NMR 1073:1078 arg1 spectroscopy 1080:1091 1H-NMR spectroscopy 1073:1091 1H-NMR spectroscopy 1073:1091 The structures of 12 of the oligosaccharides have been determined by 1H-NMR spectroscopy. 6487655 6 66 theme NMR 1175:1177 arg1 spectra 1179:1185 spectra 1179:1185 spectra 1179:1185 For those oligosaccharides which have been isolated from other sources and whose NMR spectra have been previously reported, unambiguous structural identification follows directly. 6487655 1 67 gly glycoproteins 499:511 arg1 glycoproteins 499:511 mucin glycoproteins 493:511 mucin glycoproteins 493:511 Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. 8444322 12 0 theme glycoprotein 1132:1143 arg1 forms 1145:1149 the low and high molecular weight mucus glycoprotein forms 1092:1149 the low and high molecular weight mucus glycoprotein forms of human saliva 1092:1165 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 8 1 from oligosaccharides 671:686 arg1 glycoprotein 696:707 each glycoprotein 691:707 each glycoprotein 691:707 Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. 8444322 2 2 with individuals 211:221 arg1 B 240:240 blood group B 228:240 blood group B 228:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 12 3 theme high 1104:1107 arg1 forms 1145:1149 the low and high molecular weight mucus glycoprotein forms 1092:1149 the low and high molecular weight mucus glycoprotein forms of human saliva 1092:1165 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 2 4 from forms 165:169 arg1 structure 76:84 The structure 72:84 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 72:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 0 5 from features 11:18 arg1 mucins 61:66 human salivary mucins 46:66 human salivary mucins 46:66 Structural features of carbohydrate chains in human salivary mucins. 8444322 10 6 theme sulfate 981:987 arg1 group 995:999 the sulfate ester group 977:999 the sulfate ester group at C6 of N-acetylglucosamine 977:1028 The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine. 8444322 4 7 theme acidic 379:384 arg1 alditols 408:415 neutral (55%) and acidic (45%) oligosaccharide alditols 361:415 neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units 361:456 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 12 8 theme human 1154:1158 arg1 saliva 1160:1165 human saliva 1154:1165 human saliva 1154:1165 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 4 9 dep acidic 379:384 arg1 % 389:389 45% 387:389 45% 387:389 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 2 10 from saliva 201:206 arg1 forms 165:169 the low and high molecular weight mucus glycoprotein forms 112:169 the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 112:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 2 10 from saliva 201:206 arg1 chains 102:107 carbohydrate chains 89:107 carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 89:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 2 11 theme chains 102:107 arg1 structure 76:84 The structure 72:84 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 72:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 10 12 theme sulfated 889:896 arg1 oligosaccharide 898:912 The sulfated oligosaccharide 885:912 The sulfated oligosaccharide in both glycoproteins 885:934 The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine. 8444322 10 12 theme sulfated 889:896 arg1 pentasaccharide 956:970 a pentasaccharide 954:970 a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine 954:1028 The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine. 8444322 2 13 gly glycoprotein 152:163 arg1 glycoprotein 152:163 the low and high molecular weight mucus glycoprotein forms 112:169 the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 112:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 6 14 theme neutral 478:484 arg1 oligosaccharides 486:501 The predominant neutral oligosaccharides 462:501 The predominant neutral oligosaccharides in both glycoprotein forms 462:528 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 2 15 theme weight 139:144 arg1 forms 165:169 the low and high molecular weight mucus glycoprotein forms 112:169 the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 112:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 6 16 theme sugar 553:557 arg1 units 559:563 16 and 15 sugar units 543:563 16 and 15 sugar units arranged in triantennary fashion 543:596 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 12 17 theme saliva 1160:1165 arg1 forms 1145:1149 the low and high molecular weight mucus glycoprotein forms 1092:1149 the low and high molecular weight mucus glycoprotein forms of human saliva 1092:1165 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 12 18 theme carbohydrate 1185:1196 arg1 chains 1198:1203 identical carbohydrate chains 1175:1203 identical carbohydrate chains 1175:1203 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 6 19 theme predominant 466:476 arg1 oligosaccharides 486:501 The predominant neutral oligosaccharides 462:501 The predominant neutral oligosaccharides in both glycoprotein forms 462:528 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 2 20 theme molecular 129:137 arg1 forms 165:169 the low and high molecular weight mucus glycoprotein forms 112:169 the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 112:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 2 21 from structure 76:84 arg1 forms 165:169 the low and high molecular weight mucus glycoprotein forms 112:169 the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 112:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 8 22 contain contained 709:717 arg1 Three 658:662 Three 658:662 Three 658:662 Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. 8444322 8 22 contain contained 709:717 arg1 oligosaccharides 671:686 the oligosaccharides 667:686 the oligosaccharides in each glycoprotein 667:707 Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. 8444322 8 22 contain contained 709:717 arg2 acid 726:729 sialic acid 719:729 sialic acid 719:729 Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. 8444322 2 23 theme high 124:127 arg1 forms 165:169 the low and high molecular weight mucus glycoprotein forms 112:169 the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 112:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 2 24 from chains 102:107 arg1 forms 165:169 the low and high molecular weight mucus glycoprotein forms 112:169 the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 112:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 2 24 from chains 102:107 arg1 saliva 201:206 submandibular-sublingual saliva 176:206 submandibular-sublingual saliva of individuals with blood group B 176:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 4 25 theme glycoproteins 310:322 arg1 cleavage 294:301 Alkaline borohydride reductive cleavage 263:301 Alkaline borohydride reductive cleavage of the glycoproteins 263:322 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 9 26 theme N-acetylgalactosamine 862:882 arg1 C6 856:857 C6 856:857 C6 of N-acetylgalactosamine 856:882 In two oligosaccharides sialic acid was linked to C3 of galactose and in one to C6 of N-acetylgalactosamine. 8444322 10 27 from C6 1004:1005 arg1 group 995:999 the sulfate ester group 977:999 the sulfate ester group at C6 of N-acetylglucosamine 977:1028 The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine. 8444322 12 28 theme mucus 1126:1130 arg1 forms 1145:1149 the low and high molecular weight mucus glycoprotein forms 1092:1149 the low and high molecular weight mucus glycoprotein forms of human saliva 1092:1165 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 12 29 theme molecular 1109:1117 arg1 forms 1145:1149 the low and high molecular weight mucus glycoprotein forms 1092:1149 the low and high molecular weight mucus glycoprotein forms of human saliva 1092:1165 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 10 30 from oligosaccharide 898:912 arg1 glycoproteins 922:934 both glycoproteins 917:934 both glycoproteins 917:934 The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine. 8444322 0 31 theme Structural 0:9 arg1 features 11:18 Structural features 0:18 Structural features of carbohydrate chains in human salivary mucins 0:66 Structural features of carbohydrate chains in human salivary mucins. 8444322 6 32 from oligosaccharides 486:501 arg1 forms 524:528 both glycoprotein forms 506:528 both glycoprotein forms 506:528 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 4 33 theme oligosaccharide 392:406 arg1 alditols 408:415 neutral (55%) and acidic (45%) oligosaccharide alditols 361:415 neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units 361:456 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 4 34 theme Alkaline 263:270 arg1 cleavage 294:301 Alkaline borohydride reductive cleavage 263:301 Alkaline borohydride reductive cleavage of the glycoproteins 263:322 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 0 35 theme carbohydrate 23:34 arg1 chains 36:41 carbohydrate chains 23:41 carbohydrate chains 23:41 Structural features of carbohydrate chains in human salivary mucins. 8444322 4 36 dep 16 443:444 arg1 to 440:441 to 440:441 to 440:441 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 9 37 theme sialic 800:805 arg1 acid 807:810 sialic acid 800:810 sialic acid 800:810 In two oligosaccharides sialic acid was linked to C3 of galactose and in one to C6 of N-acetylgalactosamine. 8444322 8 38 gly glycoprotein 696:707 arg1 glycoprotein 696:707 each glycoprotein 691:707 each glycoprotein 691:707 Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. 8444322 6 39 theme I 629:629 arg1 determinants 641:652 blood group B and I antigenic determinants 611:652 blood group B and I antigenic determinants 611:652 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 12 40 theme earlier 1079:1085 arg1 view 1087:1090 the earlier view 1075:1090 the earlier view 1075:1090 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 8 41 theme oligosaccharides 671:686 arg1 Three 658:662 Three 658:662 Three 658:662 Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. 8444322 8 41 theme oligosaccharides 671:686 arg1 oligosaccharides 671:686 the oligosaccharides 667:686 the oligosaccharides in each glycoprotein 667:707 Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. 8444322 6 42 contain carried 603:609 arg1 oligosaccharides 486:501 The predominant neutral oligosaccharides 462:501 The predominant neutral oligosaccharides in both glycoprotein forms 462:528 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 6 42 contain carried 603:609 arg2 determinants 641:652 blood group B and I antigenic determinants 611:652 blood group B and I antigenic determinants 611:652 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 6 43 theme B 623:623 arg1 determinants 641:652 blood group B and I antigenic determinants 611:652 blood group B and I antigenic determinants 611:652 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 4 44 theme reductive 284:292 arg1 cleavage 294:301 Alkaline borohydride reductive cleavage 263:301 Alkaline borohydride reductive cleavage of the glycoproteins 263:322 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 4 45 dep neutral 361:367 arg1 % 372:372 55% 370:372 55% 370:372 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 4 46 gly glycoproteins 310:322 arg1 glycoproteins 310:322 the glycoproteins 306:322 the glycoproteins 306:322 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 6 47 theme triantennary 577:588 arg1 fashion 590:596 triantennary fashion 577:596 triantennary fashion 577:596 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 12 48 gly glycoprotein 1132:1143 arg1 glycoprotein 1132:1143 the low and high molecular weight mucus glycoprotein forms 1092:1149 the low and high molecular weight mucus glycoprotein forms of human saliva 1092:1165 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 4 49 theme borohydride 272:282 arg1 cleavage 294:301 Alkaline borohydride reductive cleavage 263:301 Alkaline borohydride reductive cleavage of the glycoproteins 263:322 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 0 50 theme chains 36:41 arg1 features 11:18 Structural features 0:18 Structural features of carbohydrate chains in human salivary mucins 0:66 Structural features of carbohydrate chains in human salivary mucins. 8444322 2 51 theme carbohydrate 89:100 arg1 chains 102:107 carbohydrate chains 89:107 carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 89:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 2 52 theme glycoprotein 152:163 arg1 forms 165:169 the low and high molecular weight mucus glycoprotein forms 112:169 the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 112:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 2 53 theme group 234:238 arg1 B 240:240 blood group B 228:240 blood group B 228:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 0 54 theme salivary 52:59 arg1 mucins 61:66 human salivary mucins 46:66 human salivary mucins 46:66 Structural features of carbohydrate chains in human salivary mucins. 8444322 12 55 theme low 1096:1098 arg1 forms 1145:1149 the low and high molecular weight mucus glycoprotein forms 1092:1149 the low and high molecular weight mucus glycoprotein forms of human saliva 1092:1165 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 2 56 theme mucus 146:150 arg1 forms 165:169 the low and high molecular weight mucus glycoprotein forms 112:169 the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 112:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 2 57 theme blood 228:232 arg1 B 240:240 blood group B 228:240 blood group B 228:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 4 58 theme sugar 446:450 arg1 units 452:456 3 to 16 sugar units 438:456 3 to 16 sugar units 438:456 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 12 59 theme identical 1175:1183 arg1 chains 1198:1203 identical carbohydrate chains 1175:1203 identical carbohydrate chains 1175:1203 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 0 60 theme human 46:50 arg1 mucins 61:66 human salivary mucins 46:66 human salivary mucins 46:66 Structural features of carbohydrate chains in human salivary mucins. 8444322 10 61 theme N-acetylglucosamine 1010:1028 arg1 C6 1004:1005 C6 1004:1005 C6 of N-acetylglucosamine 1004:1028 The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine. 8444322 2 62 theme individuals 211:221 arg1 saliva 201:206 submandibular-sublingual saliva 176:206 submandibular-sublingual saliva of individuals with blood group B 176:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 4 63 theme neutral 361:367 arg1 alditols 408:415 neutral (55%) and acidic (45%) oligosaccharide alditols 361:415 neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units 361:456 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 6 64 theme group 617:621 arg1 B 623:623 blood group B 611:623 blood group B 611:623 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 12 65 contain contain 1167:1173 arg2 chains 1198:1203 identical carbohydrate chains 1175:1203 identical carbohydrate chains 1175:1203 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 12 65 contain contain 1167:1173 arg1 forms 1145:1149 the low and high molecular weight mucus glycoprotein forms 1092:1149 the low and high molecular weight mucus glycoprotein forms of human saliva 1092:1165 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 10 66 theme ester 989:993 arg1 group 995:999 the sulfate ester group 977:999 the sulfate ester group at C6 of N-acetylglucosamine 977:1028 The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine. 8444322 6 67 gly glycoprotein 511:522 arg1 glycoprotein 511:522 both glycoprotein forms 506:528 both glycoprotein forms 506:528 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 6 68 theme antigenic 631:639 arg1 determinants 641:652 blood group B and I antigenic determinants 611:652 blood group B and I antigenic determinants 611:652 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 9 69 attach linked 816:821 arg1 C3 826:827 C3 826:827 C3 of galactose 826:840 In two oligosaccharides sialic acid was linked to C3 of galactose and in one to C6 of N-acetylgalactosamine. 8444322 9 69 attach linked 816:821 arg3 one 849:851 one 849:851 one 849:851 In two oligosaccharides sialic acid was linked to C3 of galactose and in one to C6 of N-acetylgalactosamine. 8444322 9 69 attach linked 816:821 arg2 acid 807:810 sialic acid 800:810 sialic acid 800:810 In two oligosaccharides sialic acid was linked to C3 of galactose and in one to C6 of N-acetylgalactosamine. 8444322 9 69 attach linked 816:821 arg3 oligosaccharides 783:798 two oligosaccharides 779:798 two oligosaccharides 779:798 In two oligosaccharides sialic acid was linked to C3 of galactose and in one to C6 of N-acetylgalactosamine. 8444322 6 70 theme blood 611:615 arg1 B 623:623 blood group B 611:623 blood group B 611:623 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 9 71 theme galactose 832:840 arg1 C3 826:827 C3 826:827 C3 of galactose 826:840 In two oligosaccharides sialic acid was linked to C3 of galactose and in one to C6 of N-acetylgalactosamine. 8444322 4 72 theme alditols 408:415 arg1 population 347:356 a population 345:356 a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units 345:456 Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 8444322 10 73 with pentasaccharide 956:970 arg1 group 995:999 the sulfate ester group 977:999 the sulfate ester group at C6 of N-acetylglucosamine 977:1028 The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine. 8444322 8 74 theme sialic 719:724 arg1 acid 726:729 sialic acid 719:729 sialic acid 719:729 Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. 8444322 12 75 theme weight 1119:1124 arg1 forms 1145:1149 the low and high molecular weight mucus glycoprotein forms 1092:1149 the low and high molecular weight mucus glycoprotein forms of human saliva 1092:1165 The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. 8444322 2 76 theme submandibular-sublingual 176:199 arg1 saliva 201:206 submandibular-sublingual saliva 176:206 submandibular-sublingual saliva of individuals with blood group B 176:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 8 77 theme sugar 763:767 arg1 units 769:773 3 to 12 sugar units 755:773 3 to 12 sugar units 755:773 Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. 8444322 6 78 theme glycoprotein 511:522 arg1 forms 524:528 both glycoprotein forms 506:528 both glycoprotein forms 506:528 The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 8444322 2 79 theme low 116:118 arg1 forms 165:169 the low and high molecular weight mucus glycoprotein forms 112:169 the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B 112:240 The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 8444322 8 80 dep 12 760:761 arg1 to 757:758 to 757:758 to 757:758 Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. 8444322 10 81 gly glycoproteins 922:934 arg1 glycoproteins 922:934 both glycoproteins 917:934 both glycoproteins 917:934 The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N-acetylglucosamine. 4066681 7 0 theme same 1392:1395 arg1 oligosaccharides 1397:1412 these same oligosaccharides 1386:1412 these same oligosaccharides 1386:1412 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 6 1 theme disaccharide 1079:1090 arg1 structures 1065:1074 three neutral structures 1051:1074 three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1051:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 1 theme disaccharide 1079:1090 arg1 GalNAc-ol 1109:1117 a disaccharide GlcNAc beta (1-3)GalNAc-ol 1077:1117 a disaccharide GlcNAc beta (1-3)GalNAc-ol 1077:1117 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 10 2 theme species 2067:2073 arg1 studies 2040:2046 earlier studies 2032:2046 earlier studies of the major mucin species III, IV, and V 2032:2088 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 4 3 contain contained 718:726 arg1 Mucin 690:694 Mucin 690:694 Mucin 690:694 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 4 3 contain contained 718:726 arg2 array 742:746 a less varied array 728:746 a less varied array of discrete oligosaccharide structures 728:785 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 9 4 gly trisialylated 1942:1954 arg1 oligosaccharides 1956:1971 di- and trisialylated oligosaccharides 1934:1971 di- and trisialylated oligosaccharides not identified in other mucin species 1934:2009 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 5 5 from fractions 979:987 arg1 % 935:935 68 and 71% 926:935 % 935:935 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 5 from fractions 979:987 arg1 content 962:968 total oligosaccharide content 940:968 total oligosaccharide content in these fractions 940:987 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 6 6 theme GlcNAc 1200:1205 arg1 beta 1238:1241 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3) 1182:1247 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 7 theme Gal 1136:1138 arg1 beta 1157:1160 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3) 1120:1166 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1120:1175 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 4 8 dep contained 718:726 arg1 VI 715:716 VI 715:716 VI 715:716 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 3 9 theme performance 553:563 arg1 chromatography 572:585 sequential conventional and high performance liquid chromatography 520:585 chromatography 572:585 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 7 10 theme Gal 1529:1531 arg1 beta 1550:1553 hexasaccharide Gal beta (1-4)GlcNAc beta (1-3) 1514:1559 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 11 11 theme common 2351:2356 arg1 structures 2363:2372 common core structures 2351:2372 common core structures 2351:2372 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 9 12 contain contained 1924:1932 arg2 oligosaccharides 1956:1971 di- and trisialylated oligosaccharides 1934:1971 di- and trisialylated oligosaccharides not identified in other mucin species 1934:2009 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 12 contain contained 1924:1932 arg1 species 1908:1914 species 1908:1914 species VI 1908:1917 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 13 theme other 1991:1995 arg1 species 2003:2009 other mucin species 1991:2009 other mucin species 1991:2009 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 6 14 theme GlcNAc 1231:1236 arg1 beta 1238:1241 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3) 1182:1247 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 15 theme two 1328:1330 arg1 forms 1319:1323 the sialylated forms 1304:1323 the sialylated forms of two of these oligosaccharides 1304:1356 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 10 16 theme oligosaccharide 2122:2136 arg1 structures 2138:2147 oligosaccharide structures 2122:2147 oligosaccharide structures present in human colonic mucin 2122:2178 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 11 17 theme human 2212:2216 arg1 mucin 2226:2230 human colonic mucin 2212:2230 human colonic mucin 2212:2230 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 1 18 contain contains 97:104 arg2 components 119:128 six distinct components 106:128 six distinct components which may be separated by DEAE-cellulose chromatography 106:184 Purified human colonic mucin contains six distinct components which may be separated by DEAE-cellulose chromatography. 4066681 1 18 contain contains 97:104 arg1 mucin 91:95 Purified human colonic mucin 68:95 Purified human colonic mucin 68:95 Purified human colonic mucin contains six distinct components which may be separated by DEAE-cellulose chromatography. 4066681 8 19 theme discrete 1724:1731 arg1 oligosaccharides 1741:1756 discrete neutral oligosaccharides 1724:1756 discrete neutral oligosaccharides 1724:1756 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 2 20 theme side 241:244 arg1 chains 246:251 oligosaccharide side chains 225:251 oligosaccharide side chains 225:251 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 6 21 theme beta 1221:1224 arg1 beta 1238:1241 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3) 1182:1247 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 7 22 theme GlcNAc 1574:1579 arg1 beta 1581:1584 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta 1512:1584 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 22 theme GlcNAc 1574:1579 arg1 1-3 1587:1589 1-3 1587:1589 1-3 1587:1589 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 10 23 theme human 2160:2164 arg1 mucin 2174:2178 human colonic mucin 2160:2178 human colonic mucin 2160:2178 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 11 24 theme structures 2363:2372 arg1 variations 2337:2346 variations 2337:2346 variations of common core structures 2337:2372 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 6 25 theme beta 1157:1160 arg1 GalNAc-ol 1167:1175 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1120:1175 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1120:1175 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 25 theme beta 1157:1160 arg1 structures 1065:1074 three neutral structures 1051:1074 three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1051:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 26 theme acidic 1273:1278 arg1 components 1280:1289 two acidic components 1269:1289 two acidic components representing the sialylated forms of two of these oligosaccharides 1269:1356 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 7 27 theme alpha 1487:1491 arg1 GalNAc-ol 1498:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 27 theme alpha 1487:1491 arg1 structures 1448:1457 four additional acidic structures 1425:1457 four additional acidic structures 1425:1457 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 10 28 theme present 2149:2155 arg1 structures 2138:2147 oligosaccharide structures 2122:2147 oligosaccharide structures present in human colonic mucin 2122:2178 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 11 29 theme distinguishable 2274:2288 arg1 combinations 2290:2301 characteristic and distinguishable combinations 2255:2301 characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures 2255:2372 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 8 30 theme acidic 1772:1777 arg1 structures 1779:1788 six major acidic structures 1762:1788 six major acidic structures 1762:1788 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 7 31 theme beta 1564:1567 arg1 beta 1581:1584 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta 1512:1584 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 31 theme beta 1564:1567 arg1 1-3 1587:1589 1-3 1587:1589 1-3 1587:1589 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 32 theme disaccharide 1470:1481 arg1 GalNAc-ol 1498:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 32 theme disaccharide 1470:1481 arg1 structures 1448:1457 four additional acidic structures 1425:1457 four additional acidic structures 1425:1457 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 11 33 theme characteristic 2255:2268 arg1 combinations 2290:2301 characteristic and distinguishable combinations 2255:2301 characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures 2255:2372 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 7 34 dep beta 1581:1584 arg1 2-6 1606:1608 2-6 1606:1608 2-6 1606:1608 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 34 dep beta 1581:1584 arg1 alpha 1599:1603 NeuAc alpha 1593:1603 NeuAc alpha (2-6) 1593:1609 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 4 35 theme oligosaccharide 760:774 arg1 structures 776:785 discrete oligosaccharide structures 751:785 discrete oligosaccharide structures 751:785 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 10 36 attach present 2149:2155 arg2 structures 2138:2147 oligosaccharide structures 2122:2147 oligosaccharide structures present in human colonic mucin 2122:2178 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 10 36 attach present 2149:2155 arg1 mucin 2174:2178 human colonic mucin 2160:2178 human colonic mucin 2160:2178 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 1 37 theme Purified 68:75 arg1 mucin 91:95 Purified human colonic mucin 68:95 Purified human colonic mucin 68:95 Purified human colonic mucin contains six distinct components which may be separated by DEAE-cellulose chromatography. 4066681 6 38 dep included 1042:1049 arg1 well 1261:1264 well 1261:1264 well 1261:1264 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 1 39 theme colonic 83:89 arg1 mucin 91:95 Purified human colonic mucin 68:95 Purified human colonic mucin 68:95 Purified human colonic mucin contains six distinct components which may be separated by DEAE-cellulose chromatography. 4066681 3 40 theme oligosaccharide 383:397 arg1 chains 404:409 oligosaccharide side chains 383:409 oligosaccharide side chains 383:409 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 10 41 with conjunction 2015:2025 arg1 studies 2040:2046 earlier studies 2032:2046 earlier studies of the major mucin species III, IV, and V 2032:2088 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 4 42 theme varied 735:740 arg1 array 742:746 a less varied array 728:746 a less varied array of discrete oligosaccharide structures 728:785 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 3 43 theme remaining 430:438 arg1 species 463:469 the remaining early and late eluting species I 426:471 the remaining early and late eluting species I 426:471 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 0 44 theme Oligosaccharide 0:14 arg1 structures 16:25 Oligosaccharide structures 0:25 Oligosaccharide structures of isolated human colonic mucin species 0:65 Oligosaccharide structures of isolated human colonic mucin species. 4066681 3 45 dep determined 490:499 arg1 VI 482:483 VI 482:483 VI 482:483 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 7 46 theme GlcNAc 1543:1548 arg1 beta 1550:1553 hexasaccharide Gal beta (1-4)GlcNAc beta (1-3) 1514:1559 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 9 47 theme earlier 1868:1874 arg1 IV 1898:1899 IV 1898:1899 IV 1898:1899 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 47 theme earlier 1868:1874 arg1 species 1890:1896 the earlier eluting mucin species IV and V 1864:1905 the earlier eluting mucin species IV and V 1864:1905 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 47 theme earlier 1868:1874 arg1 V 1905:1905 V 1905:1905 V 1905:1905 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 2 48 theme abundant 267:274 arg1 species 276:282 the most abundant species 258:282 the most abundant species III, IV, and V which elute at intermediate salt concentrations 258:345 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 2 48 theme abundant 267:274 arg1 IV 289:290 IV 289:290 IV 289:290 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 2 48 theme abundant 267:274 arg1 V 297:297 V 297:297 V 297:297 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 2 48 theme abundant 267:274 arg1 III 284:286 III 284:286 III 284:286 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 7 49 theme acidic 1441:1446 arg1 -GalNAc-ol 1611:1620 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 49 theme acidic 1441:1446 arg1 GalNAc-ol 1498:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 49 theme acidic 1441:1446 arg1 structures 1448:1457 four additional acidic structures 1425:1457 four additional acidic structures 1425:1457 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 1 50 theme distinct 110:117 arg1 components 119:128 six distinct components 106:128 six distinct components which may be separated by DEAE-cellulose chromatography 106:184 Purified human colonic mucin contains six distinct components which may be separated by DEAE-cellulose chromatography. 4066681 11 51 contain possesses 2232:2240 arg2 species 2242:2248 species 2242:2248 species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures 2242:2372 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 11 51 contain possesses 2232:2240 arg1 mucin 2226:2230 human colonic mucin 2212:2230 human colonic mucin 2212:2230 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 3 52 theme glycosidase 667:677 arg1 digestion 679:687 sequential glycosidase digestion 656:687 sequential glycosidase digestion 656:687 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 4 53 theme mucin 819:823 arg1 components 825:834 the major mucin components 809:834 the major mucin components 809:834 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 3 54 theme eluting 455:461 arg1 species 463:469 the remaining early and late eluting species I 426:471 the remaining early and late eluting species I 426:471 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 0 55 theme human 39:43 arg1 species 59:65 isolated human colonic mucin species 30:65 isolated human colonic mucin species 30:65 Oligosaccharide structures of isolated human colonic mucin species. 4066681 6 56 theme sialylated 1308:1317 arg1 forms 1319:1323 the sialylated forms 1304:1323 the sialylated forms of two of these oligosaccharides 1304:1356 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 7 57 theme Neu 1483:1485 arg1 GalNAc-ol 1498:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 57 theme Neu 1483:1485 arg1 structures 1448:1457 four additional acidic structures 1425:1457 four additional acidic structures 1425:1457 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 58 theme other 1645:1649 arg1 species 1657:1663 any other mucin species 1641:1663 any other mucin species 1641:1663 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 6 59 theme mucin 1026:1030 arg1 species 1032:1038 mucin species I 1026:1040 mucin species I 1026:1040 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 3 60 theme chains 404:409 arg1 structures 369:378 the structures 365:378 the structures of oligosaccharide side chains 365:409 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 9 61 theme mucin 1884:1888 arg1 IV 1898:1899 IV 1898:1899 IV 1898:1899 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 61 theme mucin 1884:1888 arg1 species 1890:1896 the earlier eluting mucin species IV and V 1864:1905 the earlier eluting mucin species IV and V 1864:1905 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 61 theme mucin 1884:1888 arg1 V 1905:1905 V 1905:1905 V 1905:1905 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 0 62 theme mucin 53:57 arg1 species 59:65 isolated human colonic mucin species 30:65 isolated human colonic mucin species 30:65 Oligosaccharide structures of isolated human colonic mucin species. 4066681 8 63 theme eluting 1675:1681 arg1 species 1689:1695 The late eluting mucin species 1666:1695 The late eluting mucin species VI 1666:1698 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 9 64 theme eluting 1876:1882 arg1 IV 1898:1899 IV 1898:1899 IV 1898:1899 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 64 theme eluting 1876:1882 arg1 species 1890:1896 the earlier eluting mucin species IV and V 1864:1905 the earlier eluting mucin species IV and V 1864:1905 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 64 theme eluting 1876:1882 arg1 V 1905:1905 V 1905:1905 V 1905:1905 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 2 65 theme salt 327:330 arg1 concentrations 332:345 intermediate salt concentrations 314:345 intermediate salt concentrations 314:345 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 5 66 from % 935:935 arg1 fractions 979:987 these fractions 973:987 these fractions 973:987 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 3 67 dep species 463:469 arg1 I 471:471 I 471:471 I 471:471 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 11 68 with species 2242:2248 arg1 combinations 2290:2301 characteristic and distinguishable combinations 2255:2301 characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures 2255:2372 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 6 69 theme GlcNAc 1092:1097 arg1 structures 1065:1074 three neutral structures 1051:1074 three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1051:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 69 theme GlcNAc 1092:1097 arg1 GalNAc-ol 1109:1117 a disaccharide GlcNAc beta (1-3)GalNAc-ol 1077:1117 a disaccharide GlcNAc beta (1-3)GalNAc-ol 1077:1117 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 70 theme Gal 1217:1219 arg1 beta 1238:1241 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3) 1182:1247 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 5 71 from content 962:968 arg1 fractions 979:987 these fractions 973:987 these fractions 973:987 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 4 72 located observed 797:804 arg2 that 792:795 that 792:795 that 792:795 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 4 72 located observed 797:804 arg1 components 825:834 the major mucin components 809:834 the major mucin components 809:834 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 8 73 theme late 1670:1673 arg1 species 1689:1695 The late eluting mucin species 1666:1695 The late eluting mucin species VI 1666:1698 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 6 74 theme oligosaccharides 1341:1356 arg1 two 1328:1330 two 1328:1330 two 1328:1330 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 74 theme oligosaccharides 1341:1356 arg1 oligosaccharides 1341:1356 these oligosaccharides 1335:1356 these oligosaccharides 1335:1356 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 7 75 theme Mucin 1359:1363 arg1 species 1365:1371 Mucin species II 1359:1374 Mucin species II 1359:1374 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 10 76 theme mucin 2061:2065 arg1 species 2067:2073 the major mucin species 2051:2073 the major mucin species III, IV, and V 2051:2088 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 8 77 contain contained 1700:1708 arg2 structures 1779:1788 six major acidic structures 1762:1788 six major acidic structures 1762:1788 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 8 77 contain contained 1700:1708 arg2 oligosaccharides 1741:1756 discrete neutral oligosaccharides 1724:1756 discrete neutral oligosaccharides 1724:1756 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 8 77 contain contained 1700:1708 arg1 species 1689:1695 The late eluting mucin species 1666:1695 The late eluting mucin species VI 1666:1698 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 9 78 theme di- 1934:1936 arg1 oligosaccharides 1956:1971 di- and trisialylated oligosaccharides 1934:1971 di- and trisialylated oligosaccharides not identified in other mucin species 1934:2009 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 6 79 theme beta 1207:1210 arg1 beta 1238:1241 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3) 1182:1247 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 7 80 theme NeuAc 1593:1597 arg1 2-6 1606:1608 2-6 1606:1608 2-6 1606:1608 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 80 theme NeuAc 1593:1597 arg1 alpha 1599:1603 NeuAc alpha 1593:1603 NeuAc alpha (2-6) 1593:1609 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 6 81 theme beta 1140:1143 arg1 beta 1157:1160 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3) 1120:1166 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1120:1175 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 9 82 theme trisialylated 1942:1954 arg1 oligosaccharides 1956:1971 di- and trisialylated oligosaccharides 1934:1971 di- and trisialylated oligosaccharides not identified in other mucin species 1934:2009 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 6 83 theme tetrasaccharide 1184:1198 arg1 beta 1238:1241 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3) 1182:1247 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 3 84 theme liquid 565:570 arg1 chromatography 572:585 sequential conventional and high performance liquid chromatography 520:585 chromatography 572:585 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 7 85 theme beta 1533:1536 arg1 beta 1550:1553 hexasaccharide Gal beta (1-4)GlcNAc beta (1-3) 1514:1559 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 6 86 theme trisaccharide 1122:1134 arg1 beta 1157:1160 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3) 1120:1166 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1120:1175 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 2 87 dep species 276:282 arg1 species 276:282 the most abundant species 258:282 the most abundant species III, IV, and V which elute at intermediate salt concentrations 258:345 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 2 87 dep species 276:282 arg1 IV 289:290 IV 289:290 IV 289:290 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 2 87 dep species 276:282 arg1 V 297:297 V 297:297 V 297:297 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 2 87 dep species 276:282 arg1 III 284:286 III 284:286 III 284:286 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 3 88 theme high 548:551 arg1 chromatography 572:585 sequential conventional and high performance liquid chromatography 520:585 chromatography 572:585 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 5 89 theme Mucin 837:841 arg1 I 851:851 I 851:851 I 851:851 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 89 theme Mucin 837:841 arg1 species 843:849 Mucin species I and II 837:858 Mucin species I and II 837:858 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 89 theme Mucin 837:841 arg1 II 857:858 II 857:858 II 857:858 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 7 90 theme hexasaccharide 1514:1527 arg1 beta 1550:1553 hexasaccharide Gal beta (1-4)GlcNAc beta (1-3) 1514:1559 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 10 91 from present 2149:2155 arg1 mucin 2174:2178 human colonic mucin 2160:2178 human colonic mucin 2160:2178 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 6 92 theme beta 1238:1241 arg1 structures 1065:1074 three neutral structures 1051:1074 three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1051:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 92 theme beta 1238:1241 arg1 GalNAc-ol 1248:1256 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 9 93 theme mucin 1997:2001 arg1 species 2003:2009 other mucin species 1991:2009 other mucin species 1991:2009 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 8 94 theme neutral 1733:1739 arg1 oligosaccharides 1741:1756 discrete neutral oligosaccharides 1724:1756 discrete neutral oligosaccharides 1724:1756 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 2 95 theme chains 246:251 arg1 structure 212:220 the structure 208:220 the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations 208:345 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 10 96 from mucin 2174:2178 arg1 present 2149:2155 present 2149:2155 present 2149:2155 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 8 97 theme mucin 1683:1687 arg1 species 1689:1695 The late eluting mucin species 1666:1695 The late eluting mucin species VI 1666:1698 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 3 98 theme methylation 630:640 arg1 analysis 642:649 methylation analysis 630:649 methylation analysis 630:649 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 11 99 theme core 2358:2361 arg1 structures 2363:2372 common core structures 2351:2372 common core structures 2351:2372 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 3 100 theme II 474:475 arg1 species 463:469 the remaining early and late eluting species I 426:471 the remaining early and late eluting species I 426:471 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 8 101 theme major 1766:1770 arg1 structures 1779:1788 six major acidic structures 1762:1788 six major acidic structures 1762:1788 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 3 102 theme chromatography 614:627 arg1 combination 595:605 combination 595:605 combination of gas chromatography 595:627 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 3 102 theme chromatography 614:627 arg1 digestion 679:687 sequential glycosidase digestion 656:687 sequential glycosidase digestion 656:687 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 3 102 theme chromatography 614:627 arg1 analysis 642:649 methylation analysis 630:649 methylation analysis 630:649 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 7 103 contain contained 1376:1384 arg2 oligosaccharides 1397:1412 these same oligosaccharides 1386:1412 these same oligosaccharides 1386:1412 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 103 contain contained 1376:1384 arg1 species 1365:1371 Mucin species II 1359:1374 Mucin species II 1359:1374 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 104 theme beta 1581:1584 arg1 -GalNAc-ol 1611:1620 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 104 theme beta 1581:1584 arg1 structures 1448:1457 four additional acidic structures 1425:1457 four additional acidic structures 1425:1457 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 6 105 theme predominant 994:1004 arg1 oligosaccharides 1006:1021 The predominant oligosaccharides 990:1021 The predominant oligosaccharides of mucin species I 990:1040 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 8 106 dep species 1689:1695 arg1 VI 1697:1698 VI 1697:1698 VI 1697:1698 The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. 4066681 6 107 theme GlcNAc 1150:1155 arg1 beta 1157:1160 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3) 1120:1166 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1120:1175 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 11 108 theme colonic 2218:2224 arg1 mucin 2226:2230 human colonic mucin 2212:2230 human colonic mucin 2212:2230 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 1 109 theme DEAE-cellulose 156:169 arg1 chromatography 171:184 DEAE-cellulose chromatography 156:184 DEAE-cellulose chromatography 156:184 Purified human colonic mucin contains six distinct components which may be separated by DEAE-cellulose chromatography. 4066681 10 110 theme structures 2138:2147 arg1 range 2113:2117 the range 2109:2117 the range of oligosaccharide structures present in human colonic mucin 2109:2178 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 10 111 theme earlier 2032:2038 arg1 studies 2040:2046 earlier studies 2032:2046 earlier studies of the major mucin species III, IV, and V 2032:2088 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 9 112 theme structures 1819:1828 arg1 majority 1801:1808 the majority 1797:1808 the majority of these structures 1797:1828 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 6 113 gly sialylated 1308:1317 arg1 forms 1319:1323 the sialylated forms 1304:1323 the sialylated forms of two of these oligosaccharides 1304:1356 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 9 114 dep species 1890:1896 arg1 IV 1898:1899 IV 1898:1899 IV 1898:1899 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 114 dep species 1890:1896 arg1 species 1890:1896 the earlier eluting mucin species IV and V 1864:1905 the earlier eluting mucin species IV and V 1864:1905 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 114 dep species 1890:1896 arg1 V 1905:1905 V 1905:1905 V 1905:1905 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 11 115 theme oligosaccharides 2306:2321 arg1 combinations 2290:2301 characteristic and distinguishable combinations 2255:2301 characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures 2255:2372 These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures. 4066681 5 116 theme total 940:944 arg1 content 962:968 total oligosaccharide content 940:968 total oligosaccharide content in these fractions 940:987 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 117 contain contained 860:868 arg1 I 851:851 I 851:851 I 851:851 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 117 contain contained 860:868 arg1 II 857:858 II 857:858 II 857:858 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 117 contain contained 860:868 arg1 species 843:849 Mucin species I and II 837:858 Mucin species I and II 837:858 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 117 contain contained 860:868 arg2 structures 882:891 five and 10 structures 870:891 five and 10 structures 870:891 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 4 118 theme discrete 751:758 arg1 structures 776:785 discrete oligosaccharide structures 751:785 discrete oligosaccharide structures 751:785 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 9 119 attach isolated 1850:1857 arg2 majority 1801:1808 the majority 1797:1808 the majority of these structures 1797:1828 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 119 attach isolated 1850:1857 arg1 IV 1898:1899 IV 1898:1899 IV 1898:1899 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 119 attach isolated 1850:1857 arg1 species 1890:1896 the earlier eluting mucin species IV and V 1864:1905 the earlier eluting mucin species IV and V 1864:1905 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 9 119 attach isolated 1850:1857 arg1 V 1905:1905 V 1905:1905 V 1905:1905 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 1 120 theme human 77:81 arg1 mucin 91:95 Purified human colonic mucin 68:95 Purified human colonic mucin 68:95 Purified human colonic mucin contains six distinct components which may be separated by DEAE-cellulose chromatography. 4066681 7 121 theme Gal 1560:1562 arg1 beta 1581:1584 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta 1512:1584 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 121 theme Gal 1560:1562 arg1 1-3 1587:1589 1-3 1587:1589 1-3 1587:1589 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 10 122 theme colonic 2166:2172 arg1 mucin 2174:2178 human colonic mucin 2160:2178 human colonic mucin 2160:2178 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 10 123 theme major 2055:2059 arg1 species 2067:2073 the major mucin species 2051:2073 the major mucin species III, IV, and V 2051:2088 In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. 4066681 4 124 theme structures 776:785 arg1 array 742:746 a less varied array 728:746 a less varied array of discrete oligosaccharide structures 728:785 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 3 125 theme late 450:453 arg1 species 463:469 the remaining early and late eluting species I 426:471 the remaining early and late eluting species I 426:471 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 9 126 dep species 1908:1914 arg1 VI 1916:1917 VI 1916:1917 VI 1916:1917 While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. 4066681 5 127 theme 68 926:927 arg1 % 935:935 68 and 71% 926:935 % 935:935 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 127 theme 68 926:927 arg1 content 962:968 total oligosaccharide content 940:968 total oligosaccharide content in these fractions 940:987 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 6 128 theme neutral 1057:1063 arg1 GalNAc-ol 1167:1175 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1120:1175 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1120:1175 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 128 theme neutral 1057:1063 arg1 structures 1065:1074 three neutral structures 1051:1074 three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1051:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 128 theme neutral 1057:1063 arg1 GalNAc-ol 1248:1256 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 128 theme neutral 1057:1063 arg1 GalNAc-ol 1109:1117 a disaccharide GlcNAc beta (1-3)GalNAc-ol 1077:1117 a disaccharide GlcNAc beta (1-3)GalNAc-ol 1077:1117 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 3 129 theme side 399:402 arg1 chains 404:409 oligosaccharide side chains 383:409 oligosaccharide side chains 383:409 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 3 130 theme early 440:444 arg1 species 463:469 the remaining early and late eluting species I 426:471 the remaining early and late eluting species I 426:471 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 0 131 theme isolated 30:37 arg1 species 59:65 isolated human colonic mucin species 30:65 isolated human colonic mucin species 30:65 Oligosaccharide structures of isolated human colonic mucin species. 4066681 7 132 dep contained 1376:1384 arg1 -GalNAc-ol 1611:1620 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 132 dep contained 1376:1384 arg1 identified 1627:1636 identified 1627:1636 identified in any other mucin species 1627:1663 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 132 dep contained 1376:1384 arg1 GalNAc-ol 1498:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 132 dep contained 1376:1384 arg1 structures 1448:1457 four additional acidic structures 1425:1457 four additional acidic structures 1425:1457 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 5 133 theme 71 933:934 arg1 % 935:935 68 and 71% 926:935 % 935:935 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 133 theme 71 933:934 arg1 content 962:968 total oligosaccharide content 940:968 total oligosaccharide content in these fractions 940:987 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 7 134 theme beta 1550:1553 arg1 beta 1581:1584 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta 1512:1584 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 134 theme beta 1550:1553 arg1 1-3 1587:1589 1-3 1587:1589 1-3 1587:1589 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 5 135 theme oligosaccharide 946:960 arg1 content 962:968 total oligosaccharide content 940:968 total oligosaccharide content in these fractions 940:987 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 3 136 theme sequential 656:665 arg1 digestion 679:687 sequential glycosidase digestion 656:687 sequential glycosidase digestion 656:687 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 6 137 dep structures 1065:1074 arg1 GalNAc-ol 1167:1175 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1120:1175 a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1120:1175 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 137 dep structures 1065:1074 arg1 structures 1065:1074 three neutral structures 1051:1074 three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1051:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 137 dep structures 1065:1074 arg1 GalNAc-ol 1248:1256 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1182:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 137 dep structures 1065:1074 arg1 GalNAc-ol 1109:1117 a disaccharide GlcNAc beta (1-3)GalNAc-ol 1077:1117 a disaccharide GlcNAc beta (1-3)GalNAc-ol 1077:1117 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 0 138 theme colonic 45:51 arg1 species 59:65 isolated human colonic mucin species 30:65 isolated human colonic mucin species 30:65 Oligosaccharide structures of isolated human colonic mucin species. 4066681 2 139 from species 276:282 arg1 structure 212:220 the structure 208:220 the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations 208:345 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 6 140 theme species 1032:1038 arg1 oligosaccharides 1006:1021 The predominant oligosaccharides 990:1021 The predominant oligosaccharides of mucin species I 990:1040 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 2 141 theme Past 187:190 arg1 studies 192:198 Past studies 187:198 Past studies 187:198 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 4 142 theme major 813:817 arg1 components 825:834 the major mucin components 809:834 the major mucin components 809:834 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 0 143 theme species 59:65 arg1 structures 16:25 Oligosaccharide structures 0:25 Oligosaccharide structures of isolated human colonic mucin species 0:65 Oligosaccharide structures of isolated human colonic mucin species. 4066681 7 144 theme additional 1430:1439 arg1 -GalNAc-ol 1611:1620 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol 1512:1620 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 144 theme additional 1430:1439 arg1 GalNAc-ol 1498:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 a disaccharide Neu alpha (2-6)GalNAc-ol 1468:1506 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 144 theme additional 1430:1439 arg1 structures 1448:1457 four additional acidic structures 1425:1457 four additional acidic structures 1425:1457 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 7 145 theme mucin 1651:1655 arg1 species 1657:1663 any other mucin species 1641:1663 any other mucin species 1641:1663 Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. 4066681 2 146 theme oligosaccharide 225:239 arg1 chains 246:251 oligosaccharide side chains 225:251 oligosaccharide side chains 225:251 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 3 147 theme gas 610:612 arg1 chromatography 614:627 gas chromatography 610:627 gas chromatography 610:627 In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4066681 4 148 dep I 704:704 arg1 II 707:708 II 707:708 II 707:708 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 4 148 dep I 704:704 arg1 species 696:702 species 696:702 species 696:702 Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. 4066681 2 149 theme intermediate 314:325 arg1 concentrations 332:345 intermediate salt concentrations 314:345 intermediate salt concentrations 314:345 Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. 4066681 6 150 theme beta 1099:1102 arg1 structures 1065:1074 three neutral structures 1051:1074 three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol 1051:1256 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 6 150 theme beta 1099:1102 arg1 GalNAc-ol 1109:1117 a disaccharide GlcNAc beta (1-3)GalNAc-ol 1077:1117 a disaccharide GlcNAc beta (1-3)GalNAc-ol 1077:1117 The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. 4066681 5 151 dep species 843:849 arg1 I 851:851 I 851:851 I 851:851 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 151 dep species 843:849 arg1 species 843:849 Mucin species I and II 837:858 Mucin species I and II 837:858 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 151 dep species 843:849 arg1 II 857:858 II 857:858 II 857:858 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 152 theme content 962:968 arg1 % 935:935 68 and 71% 926:935 % 935:935 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4066681 5 152 theme content 962:968 arg1 content 962:968 total oligosaccharide content 940:968 total oligosaccharide content in these fractions 940:987 Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. 4008490 10 0 theme colonic 2365:2371 arg1 mucin 2373:2377 normal colonic mucin 2358:2377 normal colonic mucin 2358:2377 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 7 1 theme many 1330:1333 arg1 oligosaccharides 1335:1350 many oligosaccharides 1330:1350 many oligosaccharides 1330:1350 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 3 2 theme individual 526:535 arg1 oligosaccharides 537:552 individual oligosaccharides 526:552 individual oligosaccharides 526:552 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 7 3 theme GlcNAc 1528:1533 arg1 core 1552:1555 a GlcNAc beta (1-3)GalNAc core 1526:1555 a GlcNAc beta (1-3)GalNAc core 1526:1555 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 9 4 theme colonic 2184:2190 arg1 mucin 2192:2196 human colonic mucin 2178:2196 human colonic mucin 2178:2196 These data demonstrate that human colonic mucin contain a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures. 4008490 7 5 theme GalNAc 1545:1550 arg1 core 1552:1555 a GlcNAc beta (1-3)GalNAc core 1526:1555 a GlcNAc beta (1-3)GalNAc core 1526:1555 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 6 6 theme basic 1265:1269 arg1 structures 1272:1281 "basic" structures 1264:1281 "basic" structures 1264:1281 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 1 7 theme oligosaccharide 179:193 arg1 chains 200:205 oligosaccharide side chains 179:205 oligosaccharide side chains from the three most abundant species 179:242 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 9 8 theme wide 2208:2211 arg1 range 2213:2217 a wide range 2206:2217 a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures 2206:2301 These data demonstrate that human colonic mucin contain a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures. 4008490 1 9 theme chains 200:205 arg1 structures 165:174 the structures 161:174 the structures of oligosaccharide side chains from the three most abundant species 161:242 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 7 10 theme neutral 1721:1727 arg1 structures 1729:1738 neutral structures 1721:1738 neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues 1721:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 6 11 theme small 1248:1252 arg1 number 1254:1259 a relatively small number 1235:1259 a relatively small number of "basic" structures 1235:1281 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 9 12 contain contain 2198:2204 arg1 mucin 2192:2196 human colonic mucin 2178:2196 human colonic mucin 2178:2196 These data demonstrate that human colonic mucin contain a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures. 4008490 9 12 contain contain 2198:2204 arg2 range 2213:2217 a wide range 2206:2217 a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures 2206:2301 These data demonstrate that human colonic mucin contain a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures. 4008490 7 13 attach linked 1508:1513 arg2 residue 1500:1506 a galactosyl residue 1487:1506 a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core 1487:1555 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 13 attach linked 1508:1513 arg3 turn 1518:1521 turn 1518:1521 turn 1518:1521 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 13 attach linked 1508:1513 arg1 core 1552:1555 a GlcNAc beta (1-3)GalNAc core 1526:1555 a GlcNAc beta (1-3)GalNAc core 1526:1555 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 3 14 theme Bio-Gel 600:606 arg1 P-4 608:610 Bio-Gel P-4 600:610 Bio-Gel P-4 600:610 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 5 15 theme discrete 900:907 arg1 structures 925:934 21 discrete oligosaccharide structures 897:934 21 discrete oligosaccharide structures 897:934 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 7 16 theme acidic 1675:1680 arg1 oligosaccharides 1682:1697 all acidic oligosaccharides 1671:1697 all acidic oligosaccharides 1671:1697 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 17 dep species 1761:1767 arg1 limited 1807:1813 limited 1807:1813 limited 1807:1813 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 17 dep species 1761:1767 arg1 included 1839:1846 included 1839:1846 included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine 1839:1927 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 17 dep species 1761:1767 arg1 contained 1961:1969 contained 1961:1969 contained both sialic acid and fucose residues 1961:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 2 18 dep species 322:328 arg1 species 322:328 colonic mucin species III, IV, and V 308:343 colonic mucin species III, IV, and V 308:343 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 18 dep species 322:328 arg1 IV 335:336 IV 335:336 IV 335:336 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 18 dep species 322:328 arg1 V 343:343 V 343:343 V 343:343 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 18 dep species 322:328 arg1 III 330:332 III 330:332 III 330:332 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 3 19 theme P-2 624:626 arg1 resins 628:633 Bio-Gel P-2 resins 616:633 Bio-Gel P-2 resins 616:633 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 2 20 attach isolated 294:301 arg2 chains 282:287 Oligosaccharide side chains 261:287 Oligosaccharide side chains 261:287 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 20 attach isolated 294:301 arg1 species 322:328 colonic mucin species III, IV, and V 308:343 colonic mucin species III, IV, and V 308:343 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 20 attach isolated 294:301 arg1 IV 335:336 IV 335:336 IV 335:336 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 20 attach isolated 294:301 arg1 V 343:343 V 343:343 V 343:343 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 20 attach isolated 294:301 arg1 III 330:332 III 330:332 III 330:332 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 10 21 theme oligosaccharide 2448:2462 arg1 structures 2464:2473 oligosaccharide structures 2448:2473 oligosaccharide structures 2448:2473 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 9 22 theme core 2271:2274 arg1 structures 2292:2301 common core oligosaccharide structures 2264:2301 common core oligosaccharide structures 2264:2301 These data demonstrate that human colonic mucin contain a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures. 4008490 1 23 from species 236:242 arg1 chains 200:205 oligosaccharide side chains 179:205 oligosaccharide side chains from the three most abundant species 179:242 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 1 23 from species 236:242 arg1 structures 165:174 the structures 161:174 the structures of oligosaccharide side chains from the three most abundant species 161:242 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 2 24 theme side 277:280 arg1 chains 282:287 Oligosaccharide side chains 261:287 Oligosaccharide side chains 261:287 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 6 25 theme detailed 1115:1122 arg1 structures 1124:1133 detailed structures 1115:1133 detailed structures 1115:1133 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 4 26 theme individual 741:750 arg1 oligosaccharides 752:767 individual oligosaccharides 741:767 individual oligosaccharides 741:767 Composition and structure of individual oligosaccharides were determined by combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4008490 7 27 theme few 1818:1820 arg1 sites 1822:1826 few sites 1818:1826 few sites 1818:1826 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 9 28 theme structures 2292:2301 arg1 variations 2250:2259 variations 2250:2259 variations of common core oligosaccharide structures 2250:2301 These data demonstrate that human colonic mucin contain a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures. 4008490 3 29 theme sequential 571:580 arg1 chromatography 582:595 sequential chromatography 571:595 sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography 571:709 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 3 30 theme preparative 647:657 arg1 chromatography 696:709 preparative normal phase high performance liquid chromatography 647:709 preparative normal phase high performance liquid chromatography 647:709 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 7 31 theme acid 1785:1788 arg1 substitution 1790:1801 sialic acid substitution 1778:1801 sialic acid substitution 1778:1801 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 32 theme core 1648:1651 arg1 structure 1653:1661 the same core structure 1639:1661 the same core structure 1639:1661 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 3 33 theme phase 666:670 arg1 chromatography 696:709 preparative normal phase high performance liquid chromatography 647:709 preparative normal phase high performance liquid chromatography 647:709 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 3 34 from chromatography 582:595 arg1 resins 628:633 Bio-Gel P-2 resins 616:633 Bio-Gel P-2 resins 616:633 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 3 34 from chromatography 582:595 arg1 P-4 608:610 Bio-Gel P-4 600:610 Bio-Gel P-4 600:610 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 6 35 theme " 1270:1270 arg1 structures 1272:1281 "basic" structures 1264:1281 "basic" structures 1264:1281 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 1 36 theme colonic 66:72 arg1 mucin 74:78 Purified human colonic mucin 51:78 Purified human colonic mucin 51:78 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 2 37 theme borotritide 417:427 arg1 presence 398:405 the presence 394:405 the presence of sodium borotritide 394:427 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 4 38 theme sequential 849:858 arg1 digestion 872:880 sequential glycosidase digestion 849:880 sequential glycosidase digestion 849:880 Composition and structure of individual oligosaccharides were determined by combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4008490 7 39 theme mucin 1755:1759 arg1 species 1761:1767 the mucin species 1751:1767 the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues 1751:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 4 40 theme chromatography 807:820 arg1 combination 788:798 combination 788:798 combination of gas chromatography, methylation analysis, and sequential glycosidase digestion 788:880 Composition and structure of individual oligosaccharides were determined by combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4008490 0 41 theme Oligosaccharide 0:14 arg1 structures 16:25 Oligosaccharide structures 0:25 Oligosaccharide structures of human colonic mucin 0:48 Oligosaccharide structures of human colonic mucin. 4008490 8 42 theme oligosaccharide 2108:2122 arg1 structures 2124:2133 13, 14, and 10 oligosaccharide structures 2093:2133 13, 14, and 10 oligosaccharide structures 2093:2133 Individually, mucin species III, IV, and V were found to contain unique mixtures of 13, 14, and 10 oligosaccharide structures, respectively. 4008490 4 43 theme methylation 823:833 arg1 analysis 835:842 methylation analysis 823:842 methylation analysis 823:842 Composition and structure of individual oligosaccharides were determined by combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4008490 3 44 theme neutral 469:475 arg1 oligosaccharides 477:492 acidic and neutral oligosaccharides 458:492 acidic and neutral oligosaccharides 458:492 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 5 45 theme oligosaccharide 909:923 arg1 structures 925:934 21 discrete oligosaccharide structures 897:934 21 discrete oligosaccharide structures 897:934 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 7 46 theme chain 1618:1622 arg1 derivatives 1624:1634 linear chain derivatives 1611:1634 linear chain derivatives of the same core structure 1611:1661 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 1 47 theme distinct 103:110 arg1 components 112:121 six distinct components 99:121 six distinct components 99:121 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 7 48 attach present 1740:1746 arg2 structures 1729:1738 neutral structures 1721:1738 neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues 1721:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 48 attach present 1740:1746 arg1 species 1761:1767 the mucin species 1751:1767 the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues 1751:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 2 49 theme sodium 410:415 arg1 borotritide 417:427 sodium borotritide 410:427 sodium borotritide 410:427 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 3 50 theme acidic 458:463 arg1 oligosaccharides 477:492 acidic and neutral oligosaccharides 458:492 acidic and neutral oligosaccharides 458:492 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 0 51 theme colonic 36:42 arg1 mucin 44:48 human colonic mucin 30:48 human colonic mucin 30:48 Oligosaccharide structures of human colonic mucin. 4008490 7 52 theme sialic 1976:1981 arg1 acid 1983:1986 both sialic acid and fucose residues 1971:2006 acid 1983:1986 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 11 53 contain contains 2530:2537 arg2 subpopulations 2578:2591 structurally and functionally distinct subpopulations 2539:2591 structurally and functionally distinct subpopulations 2539:2591 These findings support the concept that colonic mucin contains structurally and functionally distinct subpopulations. 4008490 11 53 contain contains 2530:2537 arg1 mucin 2524:2528 colonic mucin 2516:2528 colonic mucin 2516:2528 These findings support the concept that colonic mucin contains structurally and functionally distinct subpopulations. 4008490 3 54 theme performance 677:687 arg1 chromatography 696:709 preparative normal phase high performance liquid chromatography 647:709 preparative normal phase high performance liquid chromatography 647:709 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 3 55 theme exchange 501:508 arg1 chromatography 510:523 ion exchange chromatography 497:523 ion exchange chromatography 497:523 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 7 56 theme terminal 1898:1905 arg1 N-acetylgalactosamine 1907:1927 the reducing terminal N-acetylgalactosamine 1885:1927 the reducing terminal N-acetylgalactosamine 1885:1927 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 57 theme structure 1392:1400 arg1 variations 1364:1373 variations 1364:1373 variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core 1364:1555 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 4 58 theme digestion 872:880 arg1 combination 788:798 combination 788:798 combination of gas chromatography, methylation analysis, and sequential glycosidase digestion 788:880 Composition and structure of individual oligosaccharides were determined by combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4008490 1 59 theme abundant 227:234 arg1 species 236:242 the three most abundant species 212:242 the three most abundant species 212:242 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 7 60 theme several 1942:1948 arg1 structures 1950:1959 several structures 1942:1959 several structures 1942:1959 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 61 theme non-branched 1566:1577 arg1 oligosaccharides 1579:1594 non-branched oligosaccharides 1566:1594 non-branched oligosaccharides 1566:1594 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 2 62 theme reductive 372:380 arg1 cleavage 382:389 alkaline borohydride reductive cleavage 351:389 alkaline borohydride reductive cleavage in the presence of sodium borotritide 351:427 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 5 63 theme major 959:963 arg1 oligosaccharides 1013:1028 10 acidic oligosaccharides 1003:1028 10 acidic oligosaccharides 1003:1028 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 5 63 theme major 959:963 arg1 species 985:991 the major human colonic mucin species 955:991 the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues 955:1103 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 5 63 theme major 959:963 arg1 structures 1045:1054 11 neutral structures 1034:1054 11 neutral structures 1034:1054 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 1 64 theme Purified 51:58 arg1 mucin 74:78 Purified human colonic mucin 51:78 Purified human colonic mucin 51:78 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 6 65 theme structures 1194:1203 arg1 variations 1221:1230 variations 1221:1230 variations of a relatively small number of "basic" structures 1221:1281 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 6 65 theme structures 1194:1203 arg1 majority 1178:1185 the majority 1174:1185 the majority of the structures identified 1174:1214 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 2 66 theme alkaline 351:358 arg1 cleavage 382:389 alkaline borohydride reductive cleavage 351:389 alkaline borohydride reductive cleavage in the presence of sodium borotritide 351:427 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 10 67 theme normal 2358:2363 arg1 mucin 2373:2377 normal colonic mucin 2358:2377 normal colonic mucin 2358:2377 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 7 68 theme alpha 1864:1868 arg1 linkage 1874:1880 alpha 2-6 linkage 1864:1880 alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine 1864:1927 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 9 69 theme human 2178:2182 arg1 mucin 2192:2196 human colonic mucin 2178:2196 human colonic mucin 2178:2196 These data demonstrate that human colonic mucin contain a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures. 4008490 2 70 theme colonic 308:314 arg1 species 322:328 colonic mucin species III, IV, and V 308:343 colonic mucin species III, IV, and V 308:343 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 70 theme colonic 308:314 arg1 IV 335:336 IV 335:336 IV 335:336 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 70 theme colonic 308:314 arg1 V 343:343 V 343:343 V 343:343 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 70 theme colonic 308:314 arg1 III 330:332 III 330:332 III 330:332 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 7 71 theme beta 1535:1538 arg1 core 1552:1555 a GlcNAc beta (1-3)GalNAc core 1526:1555 a GlcNAc beta (1-3)GalNAc core 1526:1555 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 5 72 theme human 965:969 arg1 oligosaccharides 1013:1028 10 acidic oligosaccharides 1003:1028 10 acidic oligosaccharides 1003:1028 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 5 72 theme human 965:969 arg1 species 985:991 the major human colonic mucin species 955:991 the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues 955:1103 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 5 72 theme human 965:969 arg1 structures 1045:1054 11 neutral structures 1034:1054 11 neutral structures 1034:1054 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 7 73 contain contained 1961:1969 arg1 structures 1950:1959 several structures 1942:1959 several structures 1942:1959 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 73 contain contained 1961:1969 arg2 acid 1983:1986 both sialic acid and fucose residues 1971:2006 acid 1983:1986 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 73 contain contained 1961:1969 arg2 residues 1999:2006 both sialic acid and fucose residues 1971:2006 residues 1999:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 1 74 theme side 195:198 arg1 chains 200:205 oligosaccharide side chains 179:205 oligosaccharide side chains from the three most abundant species 179:242 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 10 75 theme mucin 2373:2377 arg1 constituents 2342:2353 The major chromatographically defined constituents 2304:2353 The major chromatographically defined constituents of normal colonic mucin 2304:2377 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 6 76 theme number 1254:1259 arg1 variations 1221:1230 variations 1221:1230 variations of a relatively small number of "basic" structures 1221:1281 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 6 76 theme number 1254:1259 arg1 generalizations 1296:1310 several generalizations 1288:1310 several generalizations pertained 1288:1320 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 6 76 theme number 1254:1259 arg1 majority 1178:1185 the majority 1174:1185 the majority of the structures identified 1174:1214 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 7 77 attach derived 1708:1714 arg1 structures 1729:1738 neutral structures 1721:1738 neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues 1721:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 77 attach derived 1708:1714 arg2 oligosaccharides 1682:1697 all acidic oligosaccharides 1671:1697 all acidic oligosaccharides 1671:1697 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 6 78 theme structures 1272:1281 arg1 number 1254:1259 a relatively small number 1235:1259 a relatively small number of "basic" structures 1235:1281 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 10 79 theme distinguishable 2416:2430 arg1 combinations 2432:2443 characteristic and distinguishable combinations 2397:2443 characteristic and distinguishable combinations of oligosaccharide structures 2397:2473 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 9 80 theme oligosaccharides 2222:2237 arg1 range 2213:2217 a wide range 2206:2217 a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures 2206:2301 These data demonstrate that human colonic mucin contain a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures. 4008490 5 81 theme colonic 971:977 arg1 oligosaccharides 1013:1028 10 acidic oligosaccharides 1003:1028 10 acidic oligosaccharides 1003:1028 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 5 81 theme colonic 971:977 arg1 species 985:991 the major human colonic mucin species 955:991 the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues 955:1103 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 5 81 theme colonic 971:977 arg1 structures 1045:1054 11 neutral structures 1034:1054 11 neutral structures 1034:1054 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 10 82 theme characteristic 2397:2410 arg1 combinations 2432:2443 characteristic and distinguishable combinations 2397:2443 characteristic and distinguishable combinations of oligosaccharide structures 2397:2473 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 7 83 theme galactosyl 1489:1498 arg1 residue 1500:1506 a galactosyl residue 1487:1506 a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core 1487:1555 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 5 84 dep 12 1087:1088 arg1 to 1084:1085 to 1084:1085 to 1084:1085 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 8 85 theme mucin 2023:2027 arg1 species 2029:2035 mucin species III 2023:2039 mucin species III 2023:2039 Individually, mucin species III, IV, and V were found to contain unique mixtures of 13, 14, and 10 oligosaccharide structures, respectively. 4008490 7 86 from species 1761:1767 arg1 present 1740:1746 present 1740:1746 present 1740:1746 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 3 87 theme Bio-Gel 616:622 arg1 resins 628:633 Bio-Gel P-2 resins 616:633 Bio-Gel P-2 resins 616:633 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 5 88 theme acidic 1006:1011 arg1 oligosaccharides 1013:1028 10 acidic oligosaccharides 1003:1028 10 acidic oligosaccharides 1003:1028 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 10 89 theme structures 2464:2473 arg1 combinations 2432:2443 characteristic and distinguishable combinations 2397:2443 characteristic and distinguishable combinations of oligosaccharide structures 2397:2473 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 9 90 theme common 2264:2269 arg1 structures 2292:2301 common core oligosaccharide structures 2264:2301 common core oligosaccharide structures 2264:2301 These data demonstrate that human colonic mucin contain a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures. 4008490 3 91 theme normal 659:664 arg1 chromatography 696:709 preparative normal phase high performance liquid chromatography 647:709 preparative normal phase high performance liquid chromatography 647:709 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 1 92 theme DEAE-cellulose 126:139 arg1 chromatography 141:154 DEAE-cellulose chromatography 126:154 DEAE-cellulose chromatography 126:154 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 7 93 theme residue 1500:1506 arg1 C3 1474:1475 C3 1474:1475 C3 1474:1475 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 93 theme residue 1500:1506 arg1 C6 1481:1482 C6 1481:1482 C6 1481:1482 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 6 94 theme several 1288:1294 arg1 generalizations 1296:1310 several generalizations 1288:1310 several generalizations pertained 1288:1320 Although detailed structures were defined for each oligosaccharide, the majority of the structures identified were variations of a relatively small number of "basic" structures, and several generalizations pertained. 4008490 9 95 theme oligosaccharide 2276:2290 arg1 structures 2292:2301 common core oligosaccharide structures 2264:2301 common core oligosaccharide structures 2264:2301 These data demonstrate that human colonic mucin contain a wide range of oligosaccharides reflecting variations of common core oligosaccharide structures. 4008490 7 96 theme sialic 1778:1783 arg1 substitution 1790:1801 sialic acid substitution 1778:1801 sialic acid substitution 1778:1801 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 2 97 theme Oligosaccharide 261:275 arg1 chains 282:287 Oligosaccharide side chains 261:287 Oligosaccharide side chains 261:287 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 5 98 theme mucin 979:983 arg1 oligosaccharides 1013:1028 10 acidic oligosaccharides 1003:1028 10 acidic oligosaccharides 1003:1028 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 5 98 theme mucin 979:983 arg1 species 985:991 the major human colonic mucin species 955:991 the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues 955:1103 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 5 98 theme mucin 979:983 arg1 structures 1045:1054 11 neutral structures 1034:1054 11 neutral structures 1034:1054 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 7 99 theme structure 1653:1661 arg1 derivatives 1624:1634 linear chain derivatives 1611:1634 linear chain derivatives of the same core structure 1611:1661 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 11 100 theme distinct 2569:2576 arg1 subpopulations 2578:2591 structurally and functionally distinct subpopulations 2539:2591 structurally and functionally distinct subpopulations 2539:2591 These findings support the concept that colonic mucin contains structurally and functionally distinct subpopulations. 4008490 7 101 attach linked 1464:1469 arg2 residues 1455:1462 N-acetylglucosaminyl residues 1434:1462 N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core 1434:1555 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 101 attach linked 1464:1469 arg1 C3 1474:1475 C3 1474:1475 C3 1474:1475 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 101 attach linked 1464:1469 arg1 C6 1481:1482 C6 1481:1482 C6 1481:1482 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 102 theme same 1643:1646 arg1 structure 1653:1661 the same core structure 1639:1661 the same core structure 1639:1661 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 4 103 theme oligosaccharides 752:767 arg1 Composition 712:722 Composition 712:722 Composition 712:722 Composition and structure of individual oligosaccharides were determined by combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4008490 4 103 theme oligosaccharides 752:767 arg1 structure 728:736 structure 728:736 structure 728:736 Composition and structure of individual oligosaccharides were determined by combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4008490 1 104 from structures 165:174 arg1 species 236:242 the three most abundant species 212:242 the three most abundant species 212:242 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 1 105 theme human 60:64 arg1 mucin 74:78 Purified human colonic mucin 51:78 Purified human colonic mucin 51:78 Purified human colonic mucin was separated into six distinct components by DEAE-cellulose chromatography, and the structures of oligosaccharide side chains from the three most abundant species were determined. 4008490 2 106 theme mucin 316:320 arg1 species 322:328 colonic mucin species III, IV, and V 308:343 colonic mucin species III, IV, and V 308:343 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 106 theme mucin 316:320 arg1 IV 335:336 IV 335:336 IV 335:336 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 106 theme mucin 316:320 arg1 V 343:343 V 343:343 V 343:343 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 2 106 theme mucin 316:320 arg1 III 330:332 III 330:332 III 330:332 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 4 107 theme analysis 835:842 arg1 combination 788:798 combination 788:798 combination of gas chromatography, methylation analysis, and sequential glycosidase digestion 788:880 Composition and structure of individual oligosaccharides were determined by combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4008490 7 108 theme N-acetylglucosaminyl 1434:1453 arg1 residues 1455:1462 N-acetylglucosaminyl residues 1434:1462 N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core 1434:1555 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 10 109 theme defined 2334:2340 arg1 constituents 2342:2353 The major chromatographically defined constituents 2304:2353 The major chromatographically defined constituents of normal colonic mucin 2304:2377 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 8 110 theme unique 2074:2079 arg1 mixtures 2081:2088 unique mixtures 2074:2088 unique mixtures of 13, 14, and 10 oligosaccharide structures 2074:2133 Individually, mucin species III, IV, and V were found to contain unique mixtures of 13, 14, and 10 oligosaccharide structures, respectively. 4008490 7 111 theme fucose 1992:1997 arg1 residues 1999:2006 both sialic acid and fucose residues 1971:2006 residues 1999:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 5 112 theme neutral 1037:1043 arg1 structures 1045:1054 11 neutral structures 1034:1054 11 neutral structures 1034:1054 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 8 113 theme structures 2124:2133 arg1 mixtures 2081:2088 unique mixtures 2074:2088 unique mixtures of 13, 14, and 10 oligosaccharide structures 2074:2133 Individually, mucin species III, IV, and V were found to contain unique mixtures of 13, 14, and 10 oligosaccharide structures, respectively. 4008490 10 114 theme major 2308:2312 arg1 constituents 2342:2353 The major chromatographically defined constituents 2304:2353 The major chromatographically defined constituents of normal colonic mucin 2304:2377 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 4 115 theme gas 803:805 arg1 chromatography 807:820 gas chromatography 803:820 gas chromatography 803:820 Composition and structure of individual oligosaccharides were determined by combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4008490 3 116 theme initial 436:442 arg1 separation 444:453 initial separation 436:453 initial separation of acidic and neutral oligosaccharides by ion exchange chromatography 436:523 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 0 117 theme human 30:34 arg1 mucin 44:48 human colonic mucin 30:48 human colonic mucin 30:48 Oligosaccharide structures of human colonic mucin. 4008490 8 118 contain contain 2066:2072 arg1 species 2029:2035 mucin species III 2023:2039 mucin species III 2023:2039 Individually, mucin species III, IV, and V were found to contain unique mixtures of 13, 14, and 10 oligosaccharide structures, respectively. 4008490 8 118 contain contain 2066:2072 arg1 IV 2042:2043 IV 2042:2043 IV 2042:2043 Individually, mucin species III, IV, and V were found to contain unique mixtures of 13, 14, and 10 oligosaccharide structures, respectively. 4008490 8 118 contain contain 2066:2072 arg1 V 2050:2050 V 2050:2050 V 2050:2050 Individually, mucin species III, IV, and V were found to contain unique mixtures of 13, 14, and 10 oligosaccharide structures, respectively. 4008490 8 118 contain contain 2066:2072 arg2 mixtures 2081:2088 unique mixtures 2074:2088 unique mixtures of 13, 14, and 10 oligosaccharide structures 2074:2133 Individually, mucin species III, IV, and V were found to contain unique mixtures of 13, 14, and 10 oligosaccharide structures, respectively. 4008490 7 119 dep represented 1352:1362 arg1 appeared 1596:1603 appeared 1596:1603 appeared to be linear chain derivatives of the same core structure 1596:1661 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 119 dep represented 1352:1362 arg1 derived 1708:1714 derived 1708:1714 could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues 1699:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 120 theme branch 1411:1416 arg1 chains 1418:1423 branch chains 1411:1423 branch chains 1411:1423 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 3 121 theme liquid 689:694 arg1 chromatography 696:709 preparative normal phase high performance liquid chromatography 647:709 preparative normal phase high performance liquid chromatography 647:709 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 3 122 theme oligosaccharides 477:492 arg1 separation 444:453 initial separation 436:453 initial separation of acidic and neutral oligosaccharides by ion exchange chromatography 436:523 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 0 123 theme mucin 44:48 arg1 structures 16:25 Oligosaccharide structures 0:25 Oligosaccharide structures of human colonic mucin 0:48 Oligosaccharide structures of human colonic mucin. 4008490 7 124 theme present 1740:1746 arg1 structures 1729:1738 neutral structures 1721:1738 neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues 1721:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 3 125 theme high 672:675 arg1 chromatography 696:709 preparative normal phase high performance liquid chromatography 647:709 preparative normal phase high performance liquid chromatography 647:709 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 10 126 contain possess 2389:2395 arg1 constituents 2342:2353 The major chromatographically defined constituents 2304:2353 The major chromatographically defined constituents of normal colonic mucin 2304:2377 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 10 126 contain possess 2389:2395 arg2 combinations 2432:2443 characteristic and distinguishable combinations 2397:2443 characteristic and distinguishable combinations of oligosaccharide structures 2397:2473 The major chromatographically defined constituents of normal colonic mucin appear to possess characteristic and distinguishable combinations of oligosaccharide structures. 4008490 7 127 theme linear 1611:1616 arg1 derivatives 1624:1634 linear chain derivatives 1611:1634 linear chain derivatives of the same core structure 1611:1661 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 2 128 from cleavage 382:389 arg1 presence 398:405 the presence 394:405 the presence of sodium borotritide 394:427 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 4008490 7 129 theme biantennary 1380:1390 arg1 structure 1392:1400 a biantennary structure 1378:1400 a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core 1378:1555 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 11 130 theme colonic 2516:2522 arg1 mucin 2524:2528 colonic mucin 2516:2528 colonic mucin 2516:2528 These findings support the concept that colonic mucin contains structurally and functionally distinct subpopulations. 4008490 7 131 from present 1740:1746 arg1 species 1761:1767 the mucin species 1751:1767 the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues 1751:2006 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 4 132 theme glycosidase 860:870 arg1 digestion 872:880 sequential glycosidase digestion 849:880 sequential glycosidase digestion 849:880 Composition and structure of individual oligosaccharides were determined by combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. 4008490 3 133 theme ion 497:499 arg1 chromatography 510:523 ion exchange chromatography 497:523 ion exchange chromatography 497:523 After initial separation of acidic and neutral oligosaccharides by ion exchange chromatography, individual oligosaccharides were isolated by sequential chromatography on Bio-Gel P-4 and Bio-Gel P-2 resins followed by preparative normal phase high performance liquid chromatography. 4008490 5 134 theme sugar 1090:1094 arg1 residues 1096:1103 2 to 12 sugar residues 1082:1103 2 to 12 sugar residues 1082:1103 Collectively, 21 discrete oligosaccharide structures were identified in the major human colonic mucin species including 10 acidic oligosaccharides and 11 neutral structures which ranged in size from 2 to 12 sugar residues. 4008490 7 135 theme reducing 1889:1896 arg1 N-acetylgalactosamine 1907:1927 the reducing terminal N-acetylgalactosamine 1885:1927 the reducing terminal N-acetylgalactosamine 1885:1927 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 7 136 from substitution 1848:1859 arg1 linkage 1874:1880 alpha 2-6 linkage 1864:1880 alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine 1864:1927 First, many oligosaccharides represented variations of a biantennary structure in which branch chains arise in N-acetylglucosaminyl residues linked to C3 and C6 of a galactosyl residue linked in turn to a GlcNAc beta (1-3)GalNAc core; second, non-branched oligosaccharides appeared to be linear chain derivatives of the same core structure; third, all acidic oligosaccharides could be derived from neutral structures present in the mucin species; fourth, sialic acid substitution was limited to few sites and always included substitution in alpha 2-6 linkage to the reducing terminal N-acetylgalactosamine, and finally several structures contained both sialic acid and fucose residues. 4008490 2 137 theme borohydride 360:370 arg1 cleavage 382:389 alkaline borohydride reductive cleavage 351:389 alkaline borohydride reductive cleavage in the presence of sodium borotritide 351:427 Oligosaccharide side chains were isolated from colonic mucin species III, IV, and V after alkaline borohydride reductive cleavage in the presence of sodium borotritide. 6619131 4 0 theme three 702:706 arg1 mixture 687:693 a mixture 685:693 a mixture of the three 685:706 To determine the structures of oligosaccharides 2, 3, and 4, a mixture of the three was subjected to methylation analysis which revealed that the N-acetylgalactosaminitol was substituted at both C-3 and C-6 and other sugars at the nonreducing ends. 6619131 6 1 theme trioxide 1157:1164 arg1 oxidation 1166:1174 chromium trioxide oxidation 1148:1174 chromium trioxide oxidation 1148:1174 Anomeric configurations were determined by exoglycosidase digestions except for galactose which was analyzed by chromium trioxide oxidation. 6619131 1 2 gly glycoprotein 169:180 arg1 glycoprotein 169:180 a mucin-type glycoprotein 156:180 a mucin-type glycoprotein from a human rectal adenocarcinoma 156:215 Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). 6619131 2 3 theme Gal 292:294 arg1 beta 296:299 Gal beta 1 292:301 Gal beta 1 292:301 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 6 4 theme chromium 1148:1155 arg1 oxidation 1166:1174 chromium trioxide oxidation 1148:1174 chromium trioxide oxidation 1148:1174 Anomeric configurations were determined by exoglycosidase digestions except for galactose which was analyzed by chromium trioxide oxidation. 6619131 1 5 attach isolated 137:144 arg1 RMG 151:153 RMG 151:153 RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma) 151:216 Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). 6619131 1 5 attach isolated 137:144 arg2 oligosaccharides 95:110 Four oligosaccharides 90:110 Four oligosaccharides in the reduced form 90:130 Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). 6619131 2 6 theme GalNAc 417:422 arg1 alpha 424:428 GalNAc alpha 1 417:430 GalNAc alpha 1 417:430 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 3 7 theme RMG 619:621 arg1 treatment 606:614 alkaline borohydride treatment 585:614 alkaline borohydride treatment of RMG 585:621 The amounts of oligosaccharides 1, 2, 3, and 4 corresponded to 27, 5, 11, and 8% of the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG. 6619131 0 8 from Structures 0:9 arg1 glycoprotein 76:87 a human rectal adenocarcinoma glycoprotein 46:87 a human rectal adenocarcinoma glycoprotein 46:87 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 6619131 5 9 theme chromatography/mass 1002:1020 arg1 spectrometry 1022:1033 gas-liquid chromatography/mass spectrometry 991:1033 gas-liquid chromatography/mass spectrometry 991:1033 Desialized oligosaccharides were prepared, and the structures were deduced by analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry. 6619131 3 10 theme total 542:546 arg1 N-acetylgalactosaminitol 548:571 the total N-acetylgalactosaminitol 538:571 the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG 538:621 The amounts of oligosaccharides 1, 2, 3, and 4 corresponded to 27, 5, 11, and 8% of the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG. 6619131 3 11 theme N-acetylgalactosaminitol 548:571 arg1 N-acetylgalactosaminitol 548:571 the total N-acetylgalactosaminitol 538:571 the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG 538:621 The amounts of oligosaccharides 1, 2, 3, and 4 corresponded to 27, 5, 11, and 8% of the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG. 6619131 3 11 theme N-acetylgalactosaminitol 548:571 arg1 % 533:533 27, 5, 11, and 8% 517:533 27, 5, 11, and 8% of the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG 517:621 The amounts of oligosaccharides 1, 2, 3, and 4 corresponded to 27, 5, 11, and 8% of the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG. 6619131 0 12 gly glycoprotein 76:87 arg1 glycoprotein 76:87 a human rectal adenocarcinoma glycoprotein 46:87 a human rectal adenocarcinoma glycoprotein 46:87 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 6619131 1 13 theme mucin-type 158:167 arg1 glycoprotein 169:180 a mucin-type glycoprotein 156:180 a mucin-type glycoprotein from a human rectal adenocarcinoma 156:215 Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). 6619131 4 14 theme other 835:839 arg1 sugars 841:846 other sugars 835:846 other sugars 835:846 To determine the structures of oligosaccharides 2, 3, and 4, a mixture of the three was subjected to methylation analysis which revealed that the N-acetylgalactosaminitol was substituted at both C-3 and C-6 and other sugars at the nonreducing ends. 6619131 5 15 theme gas-liquid 991:1000 arg1 spectrometry 1022:1033 gas-liquid chromatography/mass spectrometry 991:1033 gas-liquid chromatography/mass spectrometry 991:1033 Desialized oligosaccharides were prepared, and the structures were deduced by analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry. 6619131 4 16 theme nonreducing 855:865 arg1 ends 867:870 the nonreducing ends 851:870 the nonreducing ends 851:870 To determine the structures of oligosaccharides 2, 3, and 4, a mixture of the three was subjected to methylation analysis which revealed that the N-acetylgalactosaminitol was substituted at both C-3 and C-6 and other sugars at the nonreducing ends. 6619131 4 17 theme methylation 725:735 arg1 analysis 737:744 methylation analysis 725:744 methylation analysis which revealed that the N-acetylgalactosaminitol was substituted at both C-3 and C-6 and other sugars at the nonreducing ends 725:870 To determine the structures of oligosaccharides 2, 3, and 4, a mixture of the three was subjected to methylation analysis which revealed that the N-acetylgalactosaminitol was substituted at both C-3 and C-6 and other sugars at the nonreducing ends. 6619131 2 18 theme Sia 269:271 arg1 alpha 273:277 Sia alpha 2 269:279 Sia alpha 2 269:279 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 6 19 theme Anomeric 1036:1043 arg1 configurations 1045:1058 Anomeric configurations 1036:1058 Anomeric configurations 1036:1058 Anomeric configurations were determined by exoglycosidase digestions except for galactose which was analyzed by chromium trioxide oxidation. 6619131 0 20 theme major 18:22 arg1 oligosaccharides 24:39 the major oligosaccharides 14:39 the major oligosaccharides from a human rectal adenocarcinoma glycoprotein 14:87 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 6619131 2 21 theme Sia 394:396 arg1 alpha 398:402 Sia alpha 2 394:404 Sia alpha 2 394:404 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 5 22 from spectrometry 1022:1033 arg1 analysis 951:958 analysis 951:958 analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry 951:1033 Desialized oligosaccharides were prepared, and the structures were deduced by analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry. 6619131 1 23 theme human 189:193 arg1 adenocarcinoma 202:215 a human rectal adenocarcinoma 187:215 a human rectal adenocarcinoma 187:215 Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). 6619131 2 24 theme Sia 328:330 arg1 alpha 332:336 Sia alpha 2 328:338 Sia alpha 2 328:338 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 5 25 from sugars 981:986 arg1 spectrometry 1022:1033 gas-liquid chromatography/mass spectrometry 991:1033 gas-liquid chromatography/mass spectrometry 991:1033 Desialized oligosaccharides were prepared, and the structures were deduced by analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry. 6619131 1 26 dep RMG 151:153 arg1 glycoprotein 169:180 a mucin-type glycoprotein 156:180 a mucin-type glycoprotein from a human rectal adenocarcinoma 156:215 Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). 6619131 1 27 theme rectal 195:200 arg1 adenocarcinoma 202:215 a human rectal adenocarcinoma 187:215 a human rectal adenocarcinoma 187:215 Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). 6619131 2 28 theme GlcNAc 351:356 arg1 beta 358:361 GlcNAc beta 1 351:363 GlcNAc beta 1 351:363 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 0 29 from glycoprotein 76:87 arg1 Structures 0:9 Structures 0:9 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 0:88 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 6619131 0 29 from glycoprotein 76:87 arg1 oligosaccharides 24:39 the major oligosaccharides 14:39 the major oligosaccharides from a human rectal adenocarcinoma glycoprotein 14:87 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 6619131 3 30 theme borohydride 594:604 arg1 treatment 606:614 alkaline borohydride treatment 585:614 alkaline borohydride treatment of RMG 585:621 The amounts of oligosaccharides 1, 2, 3, and 4 corresponded to 27, 5, 11, and 8% of the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG. 6619131 0 31 theme oligosaccharides 24:39 arg1 Structures 0:9 Structures 0:9 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 0:88 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 6619131 2 32 dep GalNAc-ol 376:384 arg1 leads 365:369 leads 365:369 leads to 3 365:374 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 2 33 dep GalNAc-ol 314:322 arg1 leads 303:307 leads 303:307 leads to 3 303:312 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 1 34 from adenocarcinoma 202:215 arg1 glycoprotein 169:180 a mucin-type glycoprotein 156:180 a mucin-type glycoprotein from a human rectal adenocarcinoma 156:215 Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). 6619131 0 35 theme human 48:52 arg1 glycoprotein 76:87 a human rectal adenocarcinoma glycoprotein 46:87 a human rectal adenocarcinoma glycoprotein 46:87 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 6619131 5 36 theme Desialized 873:882 arg1 oligosaccharides 884:899 Desialized oligosaccharides 873:899 Desialized oligosaccharides 873:899 Desialized oligosaccharides were prepared, and the structures were deduced by analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry. 6619131 6 37 theme exoglycosidase 1079:1092 arg1 digestions 1094:1103 exoglycosidase digestions 1079:1103 exoglycosidase digestions except for galactose which was analyzed by chromium trioxide oxidation 1079:1174 Anomeric configurations were determined by exoglycosidase digestions except for galactose which was analyzed by chromium trioxide oxidation. 6619131 5 38 from analysis 951:958 arg1 spectrometry 1022:1033 gas-liquid chromatography/mass spectrometry 991:1033 gas-liquid chromatography/mass spectrometry 991:1033 Desialized oligosaccharides were prepared, and the structures were deduced by analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry. 6619131 1 39 theme reduced 119:125 arg1 form 127:130 the reduced form 115:130 the reduced form 115:130 Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). 6619131 3 40 theme oligosaccharides 469:484 arg1 oligosaccharides 469:484 oligosaccharides 1, 2, 3, and 4 469:499 oligosaccharides 1, 2, 3, and 4 469:499 The amounts of oligosaccharides 1, 2, 3, and 4 corresponded to 27, 5, 11, and 8% of the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG. 6619131 3 40 theme oligosaccharides 469:484 arg1 amounts 458:464 The amounts 454:464 The amounts of oligosaccharides 1, 2, 3, and 4 454:499 The amounts of oligosaccharides 1, 2, 3, and 4 corresponded to 27, 5, 11, and 8% of the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG. 6619131 4 41 theme oligosaccharides 655:670 arg1 structures 641:650 the structures 637:650 the structures of oligosaccharides 2, 3, and 4 637:682 To determine the structures of oligosaccharides 2, 3, and 4, a mixture of the three was subjected to methylation analysis which revealed that the N-acetylgalactosaminitol was substituted at both C-3 and C-6 and other sugars at the nonreducing ends. 6619131 2 42 theme alpha 236:240 arg1 s2 242:243 Sia alpha s2 232:243 Sia alpha s2 232:243 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 3 43 theme alkaline 585:592 arg1 treatment 606:614 alkaline borohydride treatment 585:614 alkaline borohydride treatment of RMG 585:621 The amounts of oligosaccharides 1, 2, 3, and 4 corresponded to 27, 5, 11, and 8% of the total N-acetylgalactosaminitol produced on alkaline borohydride treatment of RMG. 6619131 0 44 theme adenocarcinoma 61:74 arg1 glycoprotein 76:87 a human rectal adenocarcinoma glycoprotein 46:87 a human rectal adenocarcinoma glycoprotein 46:87 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 6619131 2 45 theme Sia 232:234 arg1 s2 242:243 Sia alpha s2 232:243 Sia alpha s2 232:243 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 5 46 theme sugars 981:986 arg1 analysis 951:958 analysis 951:958 analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry 951:1033 Desialized oligosaccharides were prepared, and the structures were deduced by analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry. 6619131 1 47 from oligosaccharides 95:110 arg1 form 127:130 the reduced form 115:130 the reduced form 115:130 Four oligosaccharides in the reduced form were isolated from RMG (a mucin-type glycoprotein from a human rectal adenocarcinoma). 6619131 0 48 theme rectal 54:59 arg1 glycoprotein 76:87 a human rectal adenocarcinoma glycoprotein 46:87 a human rectal adenocarcinoma glycoprotein 46:87 Structures of the major oligosaccharides from a human rectal adenocarcinoma glycoprotein. 6619131 2 49 dep leads 245:249 arg1 1 229:229 1 229:229 1 229:229 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 2 49 dep leads 245:249 arg1 leads 340:344 leads 340:344 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol 340:384 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 2 49 dep leads 245:249 arg1 leads 406:410 leads 406:410 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol 406:451 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 2 49 dep leads 245:249 arg1 3 325:325 3 325:325 3 325:325 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 2 49 dep leads 245:249 arg1 leads 281:285 leads 281:285 leads to 6(Gal beta 1 leads to 3)GalNAc-ol 281:322 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 2 49 dep leads 245:249 arg1 2 266:266 2 266:266 2 266:266 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 2 50 dep GalNAc-ol 443:451 arg1 leads 432:436 leads 432:436 leads to 3 432:441 They were 1) Sia alpha s2 leads to 6GalNAc-ol; 2) Sia alpha 2 leads to 6(Gal beta 1 leads to 3)GalNAc-ol; 3) Sia alpha 2 leads to 6(GlcNAc beta 1 leads to 3)GalNAc-ol; and 4) Sia alpha 2 leads to 6(GalNAc alpha 1 leads to 3)GalNAc-ol. 6619131 5 51 theme permethylated 967:979 arg1 sugars 981:986 the permethylated sugars 963:986 the permethylated sugars on gas-liquid chromatography/mass spectrometry 963:1033 Desialized oligosaccharides were prepared, and the structures were deduced by analysis of the permethylated sugars on gas-liquid chromatography/mass spectrometry. 17050773 5 0 with patients 660:667 arg1 IgAN 674:677 IgAN 674:677 IgAN 674:677 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 6 1 theme serum 707:711 arg1 IgA 713:715 Total serum IgA 701:715 Total serum IgA 701:715 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 17050773 13 2 theme different 1734:1742 arg1 N-glycans 1744:1752 different N-glycans 1734:1752 different N-glycans 1734:1752 Furthermore, pIgA has different N-glycans, which may recruit lectins of the inflammatory pathway. 17050773 11 3 gly glycosylation 1386:1398 arg1 chains 1413:1418 IgA heavy chains 1403:1418 IgA heavy chains 1403:1418 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 11 4 theme oligomannose 1522:1533 arg1 presence 1510:1517 the presence 1506:1517 the presence of oligomannose 1506:1533 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 2 5 theme mannose-binding 254:268 arg1 lectin 270:275 mannose-binding lectin 254:275 mannose-binding lectin 254:275 Complement activation via mannose-binding lectin and the lectin pathway is associated with disease progression. 17050773 9 6 theme IgA 1163:1165 arg1 binding 1152:1158 binding 1152:1158 binding of IgA to mesangial cells 1152:1184 Furthermore, binding of IgA to mesangial cells largely was restricted to polymeric IgA. 17050773 9 7 theme mesangial 1170:1178 arg1 cells 1180:1184 mesangial cells 1170:1184 mesangial cells 1170:1184 Furthermore, binding of IgA to mesangial cells largely was restricted to polymeric IgA. 17050773 2 8 theme lectin 285:290 arg1 pathway 292:298 the lectin pathway 281:298 the lectin pathway 281:298 Complement activation via mannose-binding lectin and the lectin pathway is associated with disease progression. 17050773 14 9 from role 1839:1842 arg1 inflammation 1866:1877 glomerular inflammation 1855:1877 glomerular inflammation in IgAN 1855:1885 These results underscore the role of pIgA in glomerular inflammation in IgAN. 17050773 1 10 theme polymeric 189:197 arg1 pIgA1 205:209 pIgA1 205:209 pIgA1 205:209 IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1 (pIgA1) and complement. 17050773 1 10 theme polymeric 189:197 arg1 IgA1 199:202 polymeric IgA1 189:202 polymeric IgA1 (pIgA1) 189:210 IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1 (pIgA1) and complement. 17050773 7 11 with patients 914:921 arg1 IgAN 928:931 IgAN 928:931 IgAN 928:931 pIgA but not mIgA contained secretory IgA, and its concentration was significantly higher in patients with IgAN than in control subjects. 17050773 0 12 from role 70:73 arg1 inflammation 89:100 glomerular inflammation 78:100 glomerular inflammation in IgA nephropathy 78:119 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 12 13 from characteristic 1669:1682 arg1 conclusion 1559:1568 conclusion 1559:1568 conclusion 1559:1568 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 5 14 theme functional 557:566 arg1 properties 568:577 functional properties 557:577 functional properties 557:577 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 11 15 theme glycan 1454:1459 arg1 composition 1461:1471 glycan composition 1454:1471 glycan composition 1454:1471 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 9 16 theme polymeric 1212:1220 arg1 IgA 1222:1224 polymeric IgA 1212:1224 polymeric IgA 1212:1224 Furthermore, binding of IgA to mesangial cells largely was restricted to polymeric IgA. 17050773 11 17 theme chains 1413:1418 arg1 glycosylation 1386:1398 N-linked glycosylation 1377:1398 N-linked glycosylation of IgA heavy chains 1377:1418 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 7 18 theme control 941:947 arg1 subjects 949:956 control subjects 941:956 control subjects 941:956 pIgA but not mIgA contained secretory IgA, and its concentration was significantly higher in patients with IgAN than in control subjects. 17050773 12 19 theme pathway 1632:1638 arg1 activation 1640:1649 lectin pathway activation 1625:1649 lectin pathway activation 1625:1649 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 19 theme pathway 1632:1638 arg1 activation 1583:1592 activation 1583:1592 activation 1583:1592 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 19 theme pathway 1632:1638 arg1 binding 1571:1577 binding 1571:1577 binding 1571:1577 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 19 theme pathway 1632:1638 arg1 characteristic 1669:1682 a predominant characteristic 1655:1682 a predominant characteristic of pIgA 1655:1690 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 4 20 theme O-linked 495:502 arg1 glycosylation 504:516 aberrant O-linked glycosylation 486:516 aberrant O-linked glycosylation 486:516 IgAN is associated with abnormalities in circulating IgA, including aberrant O-linked glycosylation. 17050773 5 21 theme monomeric 625:633 arg1 IgA 635:637 highly purified monomeric IgA 609:637 highly purified monomeric IgA (mIgA) 609:644 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 5 21 theme monomeric 625:633 arg1 mIgA 640:643 mIgA 640:643 mIgA 640:643 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 3 22 theme recent 353:358 arg1 studies 360:366 recent studies 353:366 recent studies 353:366 Furthermore, recent studies have indicated a possible role for secretory IgA. 17050773 0 23 theme glomerular 78:87 arg1 inflammation 89:100 glomerular inflammation 78:100 glomerular inflammation in IgA nephropathy 78:119 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 8 24 theme control 993:999 arg1 subjects 1001:1008 control subjects 993:1008 control subjects 993:1008 Both in patients with IgAN and in control subjects, IgA binding to the GalNAc-specific lectin Helix Aspersa and to mannose-binding lectin was much stronger for pIgA than for mIgA. 17050773 10 25 theme mesangial 1246:1254 arg1 cells 1256:1260 mesangial cells 1246:1260 mesangial cells 1246:1260 Binding of pIgA to mesangial cells resulted in increased production of IL-8, predominantly with IgA from patients with IgAN. 17050773 8 26 with patients 967:974 arg1 IgAN 981:984 IgAN 981:984 IgAN 981:984 Both in patients with IgAN and in control subjects, IgA binding to the GalNAc-specific lectin Helix Aspersa and to mannose-binding lectin was much stronger for pIgA than for mIgA. 17050773 13 27 theme pathway 1801:1807 arg1 lectins 1773:1779 lectins 1773:1779 lectins of the inflammatory pathway 1773:1807 Furthermore, pIgA has different N-glycans, which may recruit lectins of the inflammatory pathway. 17050773 11 28 theme N-linked 1377:1384 arg1 glycosylation 1386:1398 N-linked glycosylation 1377:1398 N-linked glycosylation of IgA heavy chains 1377:1418 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 0 29 theme Differential 0:11 arg1 glycosylation 13:25 Differential glycosylation 0:25 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 0:120 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 11 30 from differences 1439:1449 arg1 composition 1461:1471 glycan composition 1454:1471 glycan composition 1454:1471 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 5 31 with subjects 691:698 arg1 IgAN 674:677 IgAN 674:677 IgAN 674:677 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 12 32 theme cells 1607:1611 arg1 activation 1640:1649 lectin pathway activation 1625:1649 lectin pathway activation 1625:1649 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 32 theme cells 1607:1611 arg1 activation 1583:1592 activation 1583:1592 activation 1583:1592 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 32 theme cells 1607:1611 arg1 binding 1571:1577 binding 1571:1577 binding 1571:1577 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 32 theme cells 1607:1611 arg1 characteristic 1669:1682 a predominant characteristic 1655:1682 a predominant characteristic of pIgA 1655:1690 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 3 33 theme secretory 403:411 arg1 IgA 413:415 secretory IgA 403:415 secretory IgA 403:415 Furthermore, recent studies have indicated a possible role for secretory IgA. 17050773 11 34 theme heavy 1407:1411 arg1 chains 1413:1418 IgA heavy chains 1403:1418 IgA heavy chains 1403:1418 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 8 35 theme lectin 1046:1051 arg1 Aspersa 1059:1065 the GalNAc-specific lectin Helix Aspersa 1026:1065 the GalNAc-specific lectin Helix Aspersa 1026:1065 Both in patients with IgAN and in control subjects, IgA binding to the GalNAc-specific lectin Helix Aspersa and to mannose-binding lectin was much stronger for pIgA than for mIgA. 17050773 0 36 gly glycosylation 13:25 arg1 IgA 54:56 polymeric and monomeric IgA 30:56 polymeric and monomeric IgA 30:56 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 0 37 theme IgA 54:56 arg1 glycosylation 13:25 Differential glycosylation 0:25 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 0:120 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 6 38 theme = 756:756 arg1 n 754:754 n = 11 754:759 n = 11 754:759 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 17050773 6 38 theme = 756:756 arg1 patients 744:751 patients 744:751 patients (n = 11) 744:760 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 17050773 2 39 theme disease 319:325 arg1 progression 327:337 disease progression 319:337 disease progression 319:337 Complement activation via mannose-binding lectin and the lectin pathway is associated with disease progression. 17050773 6 40 theme size 804:807 arg1 separation 809:818 size separation 804:818 size separation 804:818 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 17050773 10 41 from patients 1332:1339 arg1 IgA 1323:1325 IgA 1323:1325 IgA from patients with IgAN 1323:1349 Binding of pIgA to mesangial cells resulted in increased production of IL-8, predominantly with IgA from patients with IgAN. 17050773 10 42 theme IL-8 1298:1301 arg1 production 1284:1293 increased production 1274:1293 increased production of IL-8 1274:1301 Binding of pIgA to mesangial cells resulted in increased production of IL-8, predominantly with IgA from patients with IgAN. 17050773 10 43 with patients 1332:1339 arg1 IgAN 1346:1349 IgAN 1346:1349 IgAN 1346:1349 Binding of pIgA to mesangial cells resulted in increased production of IL-8, predominantly with IgA from patients with IgAN. 17050773 5 44 gly glycosylation 592:604 arg1 pIgA 650:653 pIgA 650:653 pIgA 650:653 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 5 44 gly glycosylation 592:604 arg1 IgA 635:637 highly purified monomeric IgA 609:637 highly purified monomeric IgA (mIgA) 609:644 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 5 44 gly glycosylation 592:604 arg1 mIgA 640:643 mIgA 640:643 mIgA 640:643 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 11 45 theme Quantitative 1352:1363 arg1 analysis 1365:1372 Quantitative analysis 1352:1372 Quantitative analysis of N-linked glycosylation of IgA heavy chains 1352:1418 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 7 46 theme secretory 849:857 arg1 IgA 859:861 secretory IgA 849:861 secretory IgA 849:861 pIgA but not mIgA contained secretory IgA, and its concentration was significantly higher in patients with IgAN than in control subjects. 17050773 6 47 theme = 786:786 arg1 n 784:784 n = 11 784:789 n = 11 784:789 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 17050773 6 47 theme = 786:786 arg1 subjects 774:781 control subjects 766:781 control subjects (n = 11) 766:790 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 17050773 14 48 theme pIgA 1847:1850 arg1 role 1839:1842 the role 1835:1842 the role of pIgA in glomerular inflammation in IgAN 1835:1885 These results underscore the role of pIgA in glomerular inflammation in IgAN. 17050773 14 49 theme glomerular 1855:1864 arg1 inflammation 1866:1877 glomerular inflammation 1855:1877 glomerular inflammation in IgAN 1855:1885 These results underscore the role of pIgA in glomerular inflammation in IgAN. 17050773 12 50 theme pIgA 1687:1690 arg1 activation 1640:1649 lectin pathway activation 1625:1649 lectin pathway activation 1625:1649 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 50 theme pIgA 1687:1690 arg1 activation 1583:1592 activation 1583:1592 activation 1583:1592 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 50 theme pIgA 1687:1690 arg1 binding 1571:1577 binding 1571:1577 binding 1571:1577 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 50 theme pIgA 1687:1690 arg1 characteristic 1669:1682 a predominant characteristic 1655:1682 a predominant characteristic of pIgA 1655:1690 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 5 51 theme pIgA 650:653 arg1 properties 568:577 functional properties 557:577 functional properties 557:577 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 5 51 theme pIgA 650:653 arg1 glycosylation 592:604 N-linked glycosylation 583:604 N-linked glycosylation 583:604 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 1 52 theme mesangial 165:173 arg1 deposition 175:184 mesangial deposition 165:184 mesangial deposition of polymeric IgA1 (pIgA1) 165:210 IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1 (pIgA1) and complement. 17050773 6 53 theme control 766:772 arg1 n 784:784 n = 11 784:789 n = 11 784:789 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 17050773 6 53 theme control 766:772 arg1 subjects 774:781 control subjects 766:781 control subjects (n = 11) 766:790 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 17050773 1 54 theme IgA1 199:202 arg1 deposition 175:184 mesangial deposition 165:184 mesangial deposition of polymeric IgA1 (pIgA1) 165:210 IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1 (pIgA1) and complement. 17050773 1 54 theme IgA1 199:202 arg1 complement 216:225 complement 216:225 complement 216:225 IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1 (pIgA1) and complement. 17050773 5 55 link N-linked 583:590 arg1 glycosylation 592:604 N-linked glycosylation 583:604 N-linked glycosylation 583:604 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 5 56 theme control 683:689 arg1 subjects 691:698 control subjects 683:698 control subjects 683:698 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 5 57 theme N-linked 583:590 arg1 glycosylation 592:604 N-linked glycosylation 583:604 N-linked glycosylation 583:604 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 1 58 theme IgA 122:124 arg1 IgAN 139:142 IgAN 139:142 IgAN 139:142 IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1 (pIgA1) and complement. 17050773 1 58 theme IgA 122:124 arg1 nephropathy 126:136 IgA nephropathy 122:136 IgA nephropathy (IgAN) 122:143 IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1 (pIgA1) and complement. 17050773 0 59 from inflammation 89:100 arg1 nephropathy 109:119 IgA nephropathy 105:119 IgA nephropathy 105:119 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 13 60 theme inflammatory 1788:1799 arg1 pathway 1801:1807 the inflammatory pathway 1784:1807 the inflammatory pathway 1784:1807 Furthermore, pIgA has different N-glycans, which may recruit lectins of the inflammatory pathway. 17050773 11 61 theme significant 1427:1437 arg1 differences 1439:1449 significant differences 1427:1449 significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose 1427:1533 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 0 62 theme possible 61:68 arg1 role 70:73 a possible role 59:73 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 0:120 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 2 63 theme Complement 228:237 arg1 activation 239:248 Complement activation 228:248 Complement activation via mannose-binding lectin and the lectin pathway 228:298 Complement activation via mannose-binding lectin and the lectin pathway is associated with disease progression. 17050773 14 64 from inflammation 1866:1877 arg1 IgAN 1882:1885 IgAN 1882:1885 IgAN 1882:1885 These results underscore the role of pIgA in glomerular inflammation in IgAN. 17050773 12 65 theme predominant 1657:1667 arg1 activation 1640:1649 lectin pathway activation 1625:1649 lectin pathway activation 1625:1649 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 65 theme predominant 1657:1667 arg1 activation 1583:1592 activation 1583:1592 activation 1583:1592 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 65 theme predominant 1657:1667 arg1 binding 1571:1577 binding 1571:1577 binding 1571:1577 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 65 theme predominant 1657:1667 arg1 characteristic 1669:1682 a predominant characteristic 1655:1682 a predominant characteristic of pIgA 1655:1690 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 66 theme lectin 1625:1630 arg1 activation 1640:1649 lectin pathway activation 1625:1649 lectin pathway activation 1625:1649 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 66 theme lectin 1625:1630 arg1 activation 1583:1592 activation 1583:1592 activation 1583:1592 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 66 theme lectin 1625:1630 arg1 binding 1571:1577 binding 1571:1577 binding 1571:1577 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 12 66 theme lectin 1625:1630 arg1 characteristic 1669:1682 a predominant characteristic 1655:1682 a predominant characteristic of pIgA 1655:1690 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 7 67 contain contained 839:847 arg1 mIgA 834:837 mIgA 834:837 pIgA but not mIgA 821:837 pIgA but not mIgA contained secretory IgA, and its concentration was significantly higher in patients with IgAN than in control subjects. 17050773 7 67 contain contained 839:847 arg1 pIgA 821:824 pIgA 821:824 pIgA but not mIgA 821:837 pIgA but not mIgA contained secretory IgA, and its concentration was significantly higher in patients with IgAN than in control subjects. 17050773 7 67 contain contained 839:847 arg2 IgA 859:861 secretory IgA 849:861 secretory IgA 849:861 pIgA but not mIgA contained secretory IgA, and its concentration was significantly higher in patients with IgAN than in control subjects. 17050773 5 68 theme IgA 635:637 arg1 properties 568:577 functional properties 557:577 functional properties 557:577 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 5 68 theme IgA 635:637 arg1 glycosylation 592:604 N-linked glycosylation 583:604 N-linked glycosylation 583:604 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 11 69 theme glycosylation 1386:1398 arg1 analysis 1365:1372 Quantitative analysis 1352:1372 Quantitative analysis of N-linked glycosylation of IgA heavy chains 1352:1418 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 0 70 theme IgA 105:107 arg1 nephropathy 109:119 IgA nephropathy 105:119 IgA nephropathy 105:119 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 10 71 theme pIgA 1238:1241 arg1 Binding 1227:1233 Binding 1227:1233 Binding of pIgA to mesangial cells 1227:1260 Binding of pIgA to mesangial cells resulted in increased production of IL-8, predominantly with IgA from patients with IgAN. 17050773 8 72 theme IgA 1011:1013 arg1 binding 1015:1021 IgA binding 1011:1021 IgA binding to the GalNAc-specific lectin Helix Aspersa and to mannose-binding lectin 1011:1095 Both in patients with IgAN and in control subjects, IgA binding to the GalNAc-specific lectin Helix Aspersa and to mannose-binding lectin was much stronger for pIgA than for mIgA. 17050773 4 73 theme aberrant 486:493 arg1 glycosylation 504:516 aberrant O-linked glycosylation 486:516 aberrant O-linked glycosylation 486:516 IgAN is associated with abnormalities in circulating IgA, including aberrant O-linked glycosylation. 17050773 4 74 link O-linked 495:502 arg1 glycosylation 504:516 aberrant O-linked glycosylation 486:516 aberrant O-linked glycosylation 486:516 IgAN is associated with abnormalities in circulating IgA, including aberrant O-linked glycosylation. 17050773 11 75 link N-linked 1377:1384 arg1 glycosylation 1386:1398 N-linked glycosylation 1377:1398 N-linked glycosylation of IgA heavy chains 1377:1418 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 3 76 theme possible 385:392 arg1 role 394:397 a possible role 383:397 a possible role for secretory IgA 383:415 Furthermore, recent studies have indicated a possible role for secretory IgA. 17050773 6 77 theme Total 701:705 arg1 IgA 713:715 Total serum IgA 701:715 Total serum IgA 701:715 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 17050773 0 78 theme polymeric 30:38 arg1 IgA 54:56 polymeric and monomeric IgA 30:56 polymeric and monomeric IgA 30:56 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 8 79 theme GalNAc-specific 1030:1044 arg1 Aspersa 1059:1065 the GalNAc-specific lectin Helix Aspersa 1026:1065 the GalNAc-specific lectin Helix Aspersa 1026:1065 Both in patients with IgAN and in control subjects, IgA binding to the GalNAc-specific lectin Helix Aspersa and to mannose-binding lectin was much stronger for pIgA than for mIgA. 17050773 5 80 theme purified 616:623 arg1 IgA 635:637 highly purified monomeric IgA 609:637 highly purified monomeric IgA (mIgA) 609:644 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 5 80 theme purified 616:623 arg1 mIgA 640:643 mIgA 640:643 mIgA 640:643 This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. 17050773 6 81 from subjects 774:781 arg1 affinity-purified 721:737 affinity-purified 721:737 affinity-purified 721:737 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 17050773 11 82 theme IgA 1403:1405 arg1 chains 1413:1418 IgA heavy chains 1403:1418 IgA heavy chains 1403:1418 Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. 17050773 0 83 theme monomeric 44:52 arg1 IgA 54:56 polymeric and monomeric IgA 30:56 polymeric and monomeric IgA 30:56 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 8 84 theme Helix 1053:1057 arg1 Aspersa 1059:1065 the GalNAc-specific lectin Helix Aspersa 1026:1065 the GalNAc-specific lectin Helix Aspersa 1026:1065 Both in patients with IgAN and in control subjects, IgA binding to the GalNAc-specific lectin Helix Aspersa and to mannose-binding lectin was much stronger for pIgA than for mIgA. 17050773 12 85 theme mesangial 1597:1605 arg1 cells 1607:1611 mesangial cells 1597:1611 mesangial cells 1597:1611 In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. 17050773 10 86 theme increased 1274:1282 arg1 production 1284:1293 increased production 1274:1293 increased production of IL-8 1274:1301 Binding of pIgA to mesangial cells resulted in increased production of IL-8, predominantly with IgA from patients with IgAN. 17050773 8 87 theme mannose-binding 1074:1088 arg1 lectin 1090:1095 mannose-binding lectin 1074:1095 mannose-binding lectin 1074:1095 Both in patients with IgAN and in control subjects, IgA binding to the GalNAc-specific lectin Helix Aspersa and to mannose-binding lectin was much stronger for pIgA than for mIgA. 17050773 13 88 contain has 1730:1732 arg1 pIgA 1725:1728 pIgA 1725:1728 pIgA 1725:1728 Furthermore, pIgA has different N-glycans, which may recruit lectins of the inflammatory pathway. 17050773 13 88 contain has 1730:1732 arg2 N-glycans 1744:1752 different N-glycans 1734:1752 different N-glycans 1734:1752 Furthermore, pIgA has different N-glycans, which may recruit lectins of the inflammatory pathway. 17050773 0 89 dep glycosylation 13:25 arg1 role 70:73 a possible role 59:73 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 0:120 Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 17050773 6 90 from patients 744:751 arg1 affinity-purified 721:737 affinity-purified 721:737 affinity-purified 721:737 Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. 23382691 11 0 theme haematological 2271:2284 arg1 cancer 2286:2291 haematological cancer 2271:2291 haematological cancer 2271:2291 The results may also provide an explanation for the reported pleiotropy and antagonistic effects of loci involved in autoimmune diseases and haematological cancer. 23382691 9 1 theme affected 1835:1842 arg1 N-glycans 1844:1852 affected N-glycans 1835:1852 affected N-glycans 1835:1852 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 4 2 theme MALDI-TOF 623:631 arg1 spectrometry 638:649 MALDI-TOF mass spectrometry 623:649 MALDI-TOF mass spectrometry (MS) 623:654 In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. 23382691 4 2 theme MALDI-TOF 623:631 arg1 MS 652:653 MS 652:653 MS 652:653 In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. 23382691 0 3 with pleiotropy 68:77 arg1 diseases 95:102 autoimmune diseases 84:102 autoimmune diseases 84:102 Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. 23382691 0 3 with pleiotropy 68:77 arg1 cancers 123:129 haematological cancers 108:129 haematological cancers 108:129 Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. 23382691 7 4 theme multiple 1394:1401 arg1 erythematosus 1303:1315 systemic lupus erythematosus 1288:1315 systemic lupus erythematosus 1288:1315 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 4 theme multiple 1394:1401 arg1 sclerosis 1403:1411 multiple sclerosis 1394:1411 multiple sclerosis 1394:1411 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 11 5 theme reported 2182:2189 arg1 pleiotropy 2191:2200 pleiotropy 2191:2200 pleiotropy 2191:2200 The results may also provide an explanation for the reported pleiotropy and antagonistic effects of loci involved in autoimmune diseases and haematological cancer. 23382691 10 6 gly glycosylation 2077:2089 arg1 protein 2110:2116 a single plasma protein 2094:2116 a single plasma protein using GWAS 2094:2127 Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein using GWAS. 23382691 8 7 theme general 1657:1663 arg1 pattern 1665:1671 the same general pattern 1648:1671 the same general pattern of changes in IgG glycosylation 1648:1703 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 1 8 theme IgG 183:185 arg1 function 196:203 IgG effector function 183:203 IgG effector function 183:203 Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. 23382691 4 9 theme Europeans 689:697 arg1 cohort 673:678 a replication cohort 659:678 a replication cohort of 1,848 Europeans 659:697 In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. 23382691 2 10 theme N-linked 319:326 arg1 glycans 332:338 N-linked IgG glycans 319:338 N-linked IgG glycans 319:338 To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. 23382691 5 11 theme same 863:866 arg1 B4GALT1 874:880 B4GALT1 874:880 B4GALT1 874:880 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 11 theme same 863:866 arg1 loci 868:871 two of the same loci 852:871 two of the same loci (B4GALT1 and MGAT3) in the replication cohort 852:917 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 11 theme same 863:866 arg1 MGAT3 886:890 MGAT3 886:890 MGAT3 886:890 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 7 12 theme ulcerative 1340:1349 arg1 erythematosus 1303:1315 systemic lupus erythematosus 1288:1315 systemic lupus erythematosus 1288:1315 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 12 theme ulcerative 1340:1349 arg1 colitis 1351:1357 ulcerative colitis 1340:1357 ulcerative colitis 1340:1357 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 5 13 theme study 741:745 arg1 results 754:760 genome-wide association study (GWAS) results 717:760 genome-wide association study (GWAS) results 717:760 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 14 theme discovery 829:837 arg1 analysis 839:846 the discovery analysis 825:846 the discovery analysis 825:846 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 4 15 theme replication 661:671 arg1 cohort 673:678 a replication cohort 659:678 a replication cohort of 1,848 Europeans 659:697 In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. 23382691 5 16 theme GWAS 748:751 arg1 results 754:760 genome-wide association study (GWAS) results 717:760 genome-wide association study (GWAS) results 717:760 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 7 17 dep erythematosus 1303:1315 arg1 e.g. 1282:1285 e.g. 1282:1285 e.g. 1282:1285 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 5 18 from loci 799:802 arg1 analysis 839:846 the discovery analysis 825:846 the discovery analysis 825:846 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 18 from loci 799:802 arg1 cohort 912:917 the replication cohort 896:917 the replication cohort 896:917 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 7 19 theme lupus 1297:1301 arg1 type 1386:1389 diabetes type 1 1377:1391 diabetes type 1 1377:1391 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 19 theme lupus 1297:1301 arg1 sclerosis 1455:1463 nodular sclerosis 1447:1463 nodular sclerosis 1447:1463 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 19 theme lupus 1297:1301 arg1 disease 1422:1428 Graves' disease 1414:1428 Graves' disease 1414:1428 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 19 theme lupus 1297:1301 arg1 arthritis 1329:1337 rheumatoid arthritis 1318:1337 rheumatoid arthritis 1318:1337 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 19 theme lupus 1297:1301 arg1 disease 1368:1374 Crohn's disease 1360:1374 Crohn's disease 1360:1374 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 19 theme lupus 1297:1301 arg1 disease 1438:1444 celiac disease 1431:1444 celiac disease 1431:1444 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 19 theme lupus 1297:1301 arg1 sclerosis 1403:1411 multiple sclerosis 1394:1411 multiple sclerosis 1394:1411 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 19 theme lupus 1297:1301 arg1 erythematosus 1303:1315 systemic lupus erythematosus 1288:1315 systemic lupus erythematosus 1288:1315 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 19 theme lupus 1297:1301 arg1 colitis 1351:1357 ulcerative colitis 1340:1357 ulcerative colitis 1340:1357 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 5 20 theme genome-wide 717:727 arg1 results 754:760 genome-wide association study (GWAS) results 717:760 genome-wide association study (GWAS) results 717:760 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 7 21 dep cancers 1488:1494 arg1 cancers 1488:1494 haematological cancers 1473:1494 haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma) 1473:1566 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 21 dep cancers 1488:1494 arg1 myeloma 1559:1565 multiple myeloma 1550:1565 multiple myeloma 1550:1565 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 21 dep cancers 1488:1494 arg1 leukaemia 1517:1525 acute lymphoblastic leukaemia 1497:1525 acute lymphoblastic leukaemia 1497:1525 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 21 dep cancers 1488:1494 arg1 lymphoma 1536:1543 Hodgkin lymphoma 1528:1543 Hodgkin lymphoma 1528:1543 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 1 22 theme immunoglobulin 149:162 arg1 IgG 167:169 IgG 167:169 IgG 167:169 Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. 23382691 1 22 theme immunoglobulin 149:162 arg1 G 164:164 immunoglobulin G 149:164 immunoglobulin G (IgG) 149:170 Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. 23382691 9 23 theme discriminative 1930:1943 arg1 power 1945:1949 substantial discriminative power 1918:1949 substantial discriminative power 1918:1949 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 5 24 theme significant 787:797 arg1 loci 799:802 9 genome-wide significant loci 773:802 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis 773:846 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 24 theme significant 787:797 arg1 × 812:812 P<2.27 × 10(-9) 805:819 P<2.27 × 10(-9) 805:819 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 7 25 theme lymphoblastic 1503:1515 arg1 cancers 1488:1494 haematological cancers 1473:1494 haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma) 1473:1566 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 25 theme lymphoblastic 1503:1515 arg1 leukaemia 1517:1525 acute lymphoblastic leukaemia 1497:1525 acute lymphoblastic leukaemia 1497:1525 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 6 26 dep glycosyltransferases 955:974 arg1 ST6GAL1 977:983 ST6GAL1 977:983 ST6GAL1 977:983 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 6 26 dep glycosyltransferases 955:974 arg1 glycosyltransferases 955:974 glycosyltransferases 955:974 glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3) 955:1010 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 6 26 dep glycosyltransferases 955:974 arg1 FUT8 995:998 FUT8 995:998 FUT8 995:998 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 6 26 dep glycosyltransferases 955:974 arg1 MGAT3 1005:1009 MGAT3 1005:1009 MGAT3 1005:1009 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 6 26 dep glycosyltransferases 955:974 arg1 B4GALT1 986:992 B4GALT1 986:992 B4GALT1 986:992 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 10 27 theme single 2096:2101 arg1 protein 2110:2116 a single plasma protein 2094:2116 a single plasma protein using GWAS 2094:2127 Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein using GWAS. 23382691 3 28 from populations 565:575 arg1 individuals 524:534 2,247 individuals 518:534 2,247 individuals from four European discovery populations 518:575 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 9 29 theme ROC-curve 1956:1964 arg1 analysis 1966:1973 a ROC-curve analysis 1954:1973 a ROC-curve analysis (area under the curve = 0.842) 1954:2004 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 5 30 theme results 754:760 arg1 Meta-analysis 700:712 Meta-analysis 700:712 Meta-analysis of genome-wide association study (GWAS) results 700:760 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 31 from loci 868:871 arg1 analysis 839:846 the discovery analysis 825:846 the discovery analysis 825:846 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 31 from loci 868:871 arg1 cohort 912:917 the replication cohort 896:917 the replication cohort 896:917 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 7 32 theme haematological 1473:1486 arg1 cancers 1488:1494 haematological cancers 1473:1494 haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma) 1473:1566 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 32 theme haematological 1473:1486 arg1 myeloma 1559:1565 multiple myeloma 1550:1565 multiple myeloma 1550:1565 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 32 theme haematological 1473:1486 arg1 leukaemia 1517:1525 acute lymphoblastic leukaemia 1497:1525 acute lymphoblastic leukaemia 1497:1525 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 32 theme haematological 1473:1486 arg1 lymphoma 1536:1543 Hodgkin lymphoma 1528:1543 Hodgkin lymphoma 1528:1543 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 3 33 theme N-glycosylation 446:460 arg1 measurements 430:441 77 quantitative measurements 414:441 77 quantitative measurements of N-glycosylation 414:460 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 0 34 theme haematological 108:121 arg1 cancers 123:129 haematological cancers 108:129 haematological cancers 108:129 Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. 23382691 3 35 from plasma 393:398 arg1 IgG 378:380 IgG 378:380 IgG from human plasma 378:398 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 5 36 dep loci 868:871 arg1 B4GALT1 874:880 B4GALT1 874:880 B4GALT1 874:880 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 36 dep loci 868:871 arg1 loci 868:871 two of the same loci 852:871 two of the same loci (B4GALT1 and MGAT3) in the replication cohort 852:917 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 36 dep loci 868:871 arg1 MGAT3 886:890 MGAT3 886:890 MGAT3 886:890 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 10 37 theme protein 2110:2116 arg1 glycosylation 2077:2089 glycosylation 2077:2089 glycosylation of a single plasma protein using GWAS 2077:2127 Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein using GWAS. 23382691 3 38 theme discovery 555:563 arg1 populations 565:575 four European discovery populations 541:575 four European discovery populations 541:575 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 3 39 theme ultra-performance 468:484 arg1 UPLC 509:512 UPLC 509:512 UPLC 509:512 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 3 39 theme ultra-performance 468:484 arg1 chromatography 493:506 ultra-performance liquid chromatography 468:506 ultra-performance liquid chromatography (UPLC) 468:513 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 9 40 theme multiple 1770:1777 arg1 traits 1792:1797 multiple IgG N-glycan traits 1770:1797 multiple IgG N-glycan traits 1770:1797 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 9 41 dep = 1997:1997 arg1 0.842 1999:2003 0.842 1999:2003 0.842 1999:2003 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 9 42 theme IgG 1779:1781 arg1 traits 1792:1797 multiple IgG N-glycan traits 1770:1797 multiple IgG N-glycan traits 1770:1797 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 0 43 theme immunoglobulin 46:59 arg1 G 61:61 human immunoglobulin G 40:61 human immunoglobulin G 40:61 Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. 23382691 7 44 theme celiac 1431:1436 arg1 disease 1438:1444 celiac disease 1431:1444 celiac disease 1431:1444 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 44 theme celiac 1431:1436 arg1 erythematosus 1303:1315 systemic lupus erythematosus 1288:1315 systemic lupus erythematosus 1288:1315 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 0 45 gly N-glycosylation 21:35 arg1 G 61:61 human immunoglobulin G 40:61 human immunoglobulin G 40:61 Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. 23382691 9 46 with cases 1861:1865 arg1 SLE 1872:1874 SLE 1872:1874 SLE 1872:1874 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 8 47 theme Follow-up 1569:1577 arg1 experiments 1590:1600 Follow-up functional experiments 1569:1600 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice 1569:1639 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 1 48 theme Fc 230:231 arg1 receptors 233:241 Fc receptors 230:241 Fc receptors 230:241 Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. 23382691 4 49 theme mass 633:636 arg1 spectrometry 638:649 MALDI-TOF mass spectrometry 623:649 MALDI-TOF mass spectrometry (MS) 623:654 In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. 23382691 4 49 theme mass 633:636 arg1 MS 652:653 MS 652:653 MS 652:653 In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. 23382691 5 50 theme of 856:857 arg1 B4GALT1 874:880 B4GALT1 874:880 B4GALT1 874:880 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 50 theme of 856:857 arg1 loci 868:871 two of the same loci 852:871 two of the same loci (B4GALT1 and MGAT3) in the replication cohort 852:917 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 50 theme of 856:857 arg1 MGAT3 886:890 MGAT3 886:890 MGAT3 886:890 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 9 51 theme biomarker 1812:1820 arg1 potential 1822:1830 biomarker potential 1812:1830 biomarker potential of affected N-glycans 1812:1852 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 8 52 theme haplodeficient 1605:1618 arg1 mice 1636:1639 haplodeficient Ikzf1 knock-out mice 1605:1639 haplodeficient Ikzf1 knock-out mice 1605:1639 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 11 53 theme autoimmune 2247:2256 arg1 diseases 2258:2265 autoimmune diseases 2247:2265 autoimmune diseases 2247:2265 The results may also provide an explanation for the reported pleiotropy and antagonistic effects of loci involved in autoimmune diseases and haematological cancer. 23382691 4 54 theme IgG 603:605 arg1 N-glycans 607:615 IgG N-glycans 603:615 IgG N-glycans 603:615 In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. 23382691 8 55 theme knock-out 1626:1634 arg1 mice 1636:1639 haplodeficient Ikzf1 knock-out mice 1605:1639 haplodeficient Ikzf1 knock-out mice 1605:1639 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 7 56 theme diabetes 1377:1384 arg1 type 1386:1389 diabetes type 1 1377:1391 diabetes type 1 1377:1391 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 56 theme diabetes 1377:1384 arg1 erythematosus 1303:1315 systemic lupus erythematosus 1288:1315 systemic lupus erythematosus 1288:1315 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 9 57 theme N-glycans 1844:1852 arg1 potential 1822:1830 biomarker potential 1812:1830 biomarker potential of affected N-glycans 1812:1852 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 2 58 theme IgG 285:287 arg1 glycosylation 289:301 IgG glycosylation 285:301 IgG glycosylation 285:301 To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. 23382691 8 59 from glycosylation 1691:1703 arg1 pattern 1665:1671 the same general pattern 1648:1671 the same general pattern of changes in IgG glycosylation 1648:1703 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 2 60 theme IgG 328:330 arg1 glycans 332:338 N-linked IgG glycans 319:338 N-linked IgG glycans 319:338 To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. 23382691 8 61 theme same 1652:1655 arg1 pattern 1665:1671 the same general pattern 1648:1671 the same general pattern of changes in IgG glycosylation 1648:1703 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 1 62 theme effector 187:194 arg1 function 196:203 IgG effector function 183:203 IgG effector function 183:203 Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. 23382691 11 63 theme antagonistic 2206:2217 arg1 effects 2219:2225 antagonistic effects 2206:2225 antagonistic effects 2206:2225 The results may also provide an explanation for the reported pleiotropy and antagonistic effects of loci involved in autoimmune diseases and haematological cancer. 23382691 6 64 dep glycosylation 1103:1115 arg1 SUV420H1 1155:1162 SUV420H1 1155:1162 SUV420H1 1155:1162 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 6 64 dep glycosylation 1103:1115 arg1 SMARCB1-DERL3 1169:1181 SMARCB1-DERL3 1169:1181 SMARCB1-DERL3 1169:1181 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 6 64 dep glycosylation 1103:1115 arg1 ABCF2-SMARCD3 1140:1152 ABCF2-SMARCD3 1140:1152 ABCF2-SMARCD3 1140:1152 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 6 64 dep glycosylation 1103:1115 arg1 IL6ST-ANKRD55 1125:1137 IL6ST-ANKRD55 1125:1137 IL6ST-ANKRD55 1125:1137 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 6 64 dep glycosylation 1103:1115 arg1 IKZF1 1118:1122 IKZF1 1118:1122 IKZF1 1118:1122 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 1 65 gly Glycosylation 132:144 arg1 IgG 167:169 IgG 167:169 IgG 167:169 Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. 23382691 1 65 gly Glycosylation 132:144 arg1 G 164:164 immunoglobulin G 149:164 immunoglobulin G (IgG) 149:170 Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. 23382691 7 66 theme multiple 1550:1557 arg1 cancers 1488:1494 haematological cancers 1473:1494 haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma) 1473:1566 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 66 theme multiple 1550:1557 arg1 myeloma 1559:1565 multiple myeloma 1550:1565 multiple myeloma 1550:1565 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 10 67 theme new 2055:2057 arg1 loci 2059:2062 new loci 2055:2062 new loci that control glycosylation of a single plasma protein using GWAS 2055:2127 Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein using GWAS. 23382691 4 68 theme 1,848 683:687 arg1 Europeans 689:697 1,848 Europeans 683:697 1,848 Europeans 683:697 In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. 23382691 9 69 dep analysis 1966:1973 arg1 area 1976:1979 area 1976:1979 area under the curve = 0.842 1976:2003 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 9 70 theme matched 1884:1890 arg1 controls 1892:1899 183 matched controls 1880:1899 183 matched controls 1880:1899 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 8 71 theme IgG 1687:1689 arg1 glycosylation 1691:1703 IgG glycosylation 1687:1703 IgG glycosylation 1687:1703 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 7 72 theme Hodgkin 1528:1534 arg1 cancers 1488:1494 haematological cancers 1473:1494 haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma) 1473:1566 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 72 theme Hodgkin 1528:1534 arg1 lymphoma 1536:1543 Hodgkin lymphoma 1528:1543 Hodgkin lymphoma 1528:1543 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 5 73 theme association 729:739 arg1 results 754:760 genome-wide association study (GWAS) results 717:760 genome-wide association study (GWAS) results 717:760 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 6 74 contain contained 1035:1043 arg2 genes 1045:1049 genes 1045:1049 genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3) 1045:1182 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 6 74 contain contained 1035:1043 arg1 5 1033:1033 5 1033:1033 5 1033:1033 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 7 75 theme rheumatoid 1318:1327 arg1 erythematosus 1303:1315 systemic lupus erythematosus 1288:1315 systemic lupus erythematosus 1288:1315 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 75 theme rheumatoid 1318:1327 arg1 arthritis 1329:1337 rheumatoid arthritis 1318:1337 rheumatoid arthritis 1318:1337 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 2 76 link N-linked 319:326 arg1 glycans 332:338 N-linked IgG glycans 319:338 N-linked IgG glycans 319:338 To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. 23382691 6 77 theme protein 1095:1101 arg1 glycosylation 1103:1115 protein glycosylation 1095:1115 protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3) 1095:1182 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 9 78 theme substantial 1918:1928 arg1 power 1945:1949 substantial discriminative power 1918:1949 substantial discriminative power 1918:1949 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 5 79 theme genome-wide 775:785 arg1 loci 799:802 9 genome-wide significant loci 773:802 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis 773:846 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 5 79 theme genome-wide 775:785 arg1 × 812:812 P<2.27 × 10(-9) 805:819 P<2.27 × 10(-9) 805:819 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 2 80 theme genetic 256:262 arg1 loci 264:267 genetic loci 256:267 genetic loci associated with IgG glycosylation 256:301 To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. 23382691 1 81 theme G 164:164 arg1 Glycosylation 132:144 Glycosylation 132:144 Glycosylation of immunoglobulin G (IgG) 132:170 Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. 23382691 7 82 theme acute 1497:1501 arg1 cancers 1488:1494 haematological cancers 1473:1494 haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma) 1473:1566 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 82 theme acute 1497:1501 arg1 leukaemia 1517:1525 acute lymphoblastic leukaemia 1497:1525 acute lymphoblastic leukaemia 1497:1525 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 83 theme systemic 1288:1295 arg1 type 1386:1389 diabetes type 1 1377:1391 diabetes type 1 1377:1391 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 83 theme systemic 1288:1295 arg1 sclerosis 1455:1463 nodular sclerosis 1447:1463 nodular sclerosis 1447:1463 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 83 theme systemic 1288:1295 arg1 disease 1422:1428 Graves' disease 1414:1428 Graves' disease 1414:1428 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 83 theme systemic 1288:1295 arg1 arthritis 1329:1337 rheumatoid arthritis 1318:1337 rheumatoid arthritis 1318:1337 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 83 theme systemic 1288:1295 arg1 disease 1368:1374 Crohn's disease 1360:1374 Crohn's disease 1360:1374 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 83 theme systemic 1288:1295 arg1 disease 1438:1444 celiac disease 1431:1444 celiac disease 1431:1444 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 83 theme systemic 1288:1295 arg1 sclerosis 1403:1411 multiple sclerosis 1394:1411 multiple sclerosis 1394:1411 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 83 theme systemic 1288:1295 arg1 erythematosus 1303:1315 systemic lupus erythematosus 1288:1315 systemic lupus erythematosus 1288:1315 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 83 theme systemic 1288:1295 arg1 colitis 1351:1357 ulcerative colitis 1340:1357 ulcerative colitis 1340:1357 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 10 84 theme plasma 2103:2108 arg1 protein 2110:2116 a single plasma protein 2094:2116 a single plasma protein using GWAS 2094:2127 Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein using GWAS. 23382691 0 85 theme autoimmune 84:93 arg1 diseases 95:102 autoimmune diseases 84:102 autoimmune diseases 84:102 Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. 23382691 8 86 from experiments 1590:1600 arg1 mice 1636:1639 haplodeficient Ikzf1 knock-out mice 1605:1639 haplodeficient Ikzf1 knock-out mice 1605:1639 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 9 87 with controls 1892:1899 arg1 SLE 1872:1874 SLE 1872:1874 SLE 1872:1874 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 5 88 theme replication 900:910 arg1 cohort 912:917 the replication cohort 896:917 the replication cohort 896:917 Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. 23382691 7 89 theme inflammatory 1257:1268 arg1 conditions 1270:1279 autoimmune and inflammatory conditions 1242:1279 autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) 1242:1464 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 90 theme autoimmune 1242:1251 arg1 conditions 1270:1279 autoimmune and inflammatory conditions 1242:1279 autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) 1242:1464 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 3 91 theme human 387:391 arg1 plasma 393:398 human plasma 387:398 human plasma 387:398 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 9 92 theme = 1997:1997 arg1 area 1976:1979 area 1976:1979 area under the curve = 0.842 1976:2003 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 8 93 theme changes 1676:1682 arg1 pattern 1665:1671 the same general pattern 1648:1671 the same general pattern of changes in IgG glycosylation 1648:1703 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 0 94 theme human 40:44 arg1 G 61:61 human immunoglobulin G 40:61 human immunoglobulin G 40:61 Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. 23382691 3 95 theme quantitative 417:428 arg1 measurements 430:441 77 quantitative measurements 414:441 77 quantitative measurements of N-glycosylation 414:460 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 6 96 contain contained 930:938 arg2 genes 940:944 genes 940:944 genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3) 940:1010 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 6 96 contain contained 930:938 arg1 loci 925:928 Four loci 920:928 Four loci 920:928 Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). 23382691 3 97 theme liquid 486:491 arg1 UPLC 509:512 UPLC 509:512 UPLC 509:512 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 3 97 theme liquid 486:491 arg1 chromatography 493:506 ultra-performance liquid chromatography 468:506 ultra-performance liquid chromatography (UPLC) 468:513 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 0 98 theme G 61:61 arg1 N-glycosylation 21:35 N-glycosylation 21:35 N-glycosylation of human immunoglobulin G 21:61 Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. 23382691 7 99 theme nodular 1447:1453 arg1 erythematosus 1303:1315 systemic lupus erythematosus 1288:1315 systemic lupus erythematosus 1288:1315 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 7 99 theme nodular 1447:1453 arg1 sclerosis 1455:1463 nodular sclerosis 1447:1463 nodular sclerosis 1447:1463 However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). 23382691 9 100 theme N-glycan 1783:1790 arg1 traits 1792:1797 multiple IgG N-glycan traits 1770:1797 multiple IgG N-glycan traits 1770:1797 As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). 23382691 8 101 theme functional 1579:1588 arg1 experiments 1590:1600 Follow-up functional experiments 1569:1600 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice 1569:1639 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 8 102 from changes 1676:1682 arg1 glycosylation 1691:1703 IgG glycosylation 1687:1703 IgG glycosylation 1687:1703 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 11 103 theme loci 2230:2233 arg1 pleiotropy 2191:2200 pleiotropy 2191:2200 pleiotropy 2191:2200 The results may also provide an explanation for the reported pleiotropy and antagonistic effects of loci involved in autoimmune diseases and haematological cancer. 23382691 11 103 theme loci 2230:2233 arg1 effects 2219:2225 antagonistic effects 2206:2225 antagonistic effects 2206:2225 The results may also provide an explanation for the reported pleiotropy and antagonistic effects of loci involved in autoimmune diseases and haematological cancer. 23382691 8 104 from pattern 1665:1671 arg1 glycosylation 1691:1703 IgG glycosylation 1687:1703 IgG glycosylation 1687:1703 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 23382691 3 105 theme European 546:553 arg1 populations 565:575 four European discovery populations 541:575 four European discovery populations 541:575 After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. 23382691 8 106 theme Ikzf1 1620:1624 arg1 mice 1636:1639 haplodeficient Ikzf1 knock-out mice 1605:1639 haplodeficient Ikzf1 knock-out mice 1605:1639 Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. 9180155 0 0 theme new 72:74 arg1 antibody 87:94 a new monoclonal antibody 70:94 a new monoclonal antibody (VK-8) 70:101 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 0 0 theme new 72:74 arg1 VK-8 97:100 VK-8 97:100 VK-8 97:100 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 1 1 theme OVCAR-3 272:278 arg1 cells 295:299 OVCAR-3 ovarian cancer cells 272:299 OVCAR-3 ovarian cancer cells 272:299 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 2 2 from serine 585:590 arg1 rich 577:580 rich 577:580 rich 577:580 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 3 gly fucosylated 838:848 arg1 Type 850:853 fucosylated Type 2 838:855 fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures 838:909 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 1 4 theme CA 204:205 arg1 antigen 226:232 the CA 125 ovarian cancer antigen 200:232 the CA 125 ovarian cancer antigen 200:232 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 4 5 theme OC125 1173:1177 arg1 antibodies 1216:1225 OC125, the original MAb to CA125, and VK-8 antibodies 1173:1225 OC125, the original MAb to CA125, and VK-8 antibodies 1173:1225 Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. 9180155 1 6 theme ovarian 280:286 arg1 cells 295:299 OVCAR-3 ovarian cancer cells 272:299 OVCAR-3 ovarian cancer cells 272:299 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 2 7 dep O-linked 722:729 arg1 O-linked 722:729 O-linked 722:729 O-linked 722:729 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 7 dep O-linked 722:729 arg1 4 681:681 4 681:681 4 681:681 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 7 dep O-linked 722:729 arg1 chains 695:700 the glycan chains 684:700 the glycan chains 684:700 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 3 8 theme proteolytic 1023:1033 arg1 enzymes 1035:1041 proteolytic enzymes 1023:1041 proteolytic enzymes to smaller fragments that no longer reacted with the antibody 1023:1103 The antigen exhibited a very high m.w. (> 10(3) kDa) in aqueous buffer as well as in urea, but was degraded by proteolytic enzymes to smaller fragments that no longer reacted with the antibody. 9180155 2 9 theme core 737:740 arg1 [Galbeta1 744:752 core 2 [Galbeta1 --> 3 737:758 core 2 [Galbeta1 --> 3 737:758 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 10 with rich 577:580 arg1 [Galbeta1 744:752 core 2 [Galbeta1 --> 3 737:758 core 2 [Galbeta1 --> 3 737:758 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 1 11 theme cancer 288:293 arg1 cells 295:299 OVCAR-3 ovarian cancer cells 272:299 OVCAR-3 ovarian cancer cells 272:299 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 3 12 dep 10 954:955 arg1 3 957:957 3 957:957 3 957:957 The antigen exhibited a very high m.w. (> 10(3) kDa) in aqueous buffer as well as in urea, but was degraded by proteolytic enzymes to smaller fragments that no longer reacted with the antibody. 9180155 2 13 theme protein 559:565 arg1 moiety 567:572 the protein moiety 555:572 the protein moiety 555:572 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 13 theme protein 559:565 arg1 glycosylated 456:467 glycosylated 456:467 glycosylated 456:467 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 14 gly glycosylated 456:467 arg1 --> 772:774 GlcNAcbeta1 --> 6 760:776 GlcNAcbeta1 --> 6 760:776 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 14 gly glycosylated 456:467 arg1 moiety 567:572 the protein moiety 555:572 the protein moiety 555:572 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 14 gly glycosylated 456:467 arg1 glycosylated 456:467 glycosylated 456:467 glycosylated 456:467 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 14 gly glycosylated 456:467 arg1 molecule 437:444 the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3 433:758 the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures 433:795 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 1 15 theme ovarian 211:217 arg1 antigen 226:232 the CA 125 ovarian cancer antigen 200:232 the CA 125 ovarian cancer antigen 200:232 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 0 16 theme monoclonal 76:85 arg1 antibody 87:94 a new monoclonal antibody 70:94 a new monoclonal antibody (VK-8) 70:101 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 0 16 theme monoclonal 76:85 arg1 VK-8 97:100 VK-8 97:100 VK-8 97:100 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 1 17 used used 239:242 arg2 MAb 179:181 MAb VK-8 179:186 MAb VK-8 179:186 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 1 17 used used 239:242 arg2 antibody 169:176 A new murine monoclonal antibody 145:176 A new murine monoclonal antibody (MAb VK-8) 145:187 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 4 18 theme protein 1250:1256 arg1 portion 1258:1264 the protein portion 1246:1264 the protein portion of the molecule 1246:1280 Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. 9180155 2 19 theme serine 632:637 arg1 residues 653:660 the serine and threonine residues 628:660 residues 653:660 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 1 20 theme cancer 219:224 arg1 antigen 226:232 the CA 125 ovarian cancer antigen 200:232 the CA 125 ovarian cancer antigen 200:232 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 2 21 theme glycan 688:693 arg1 O-linked 722:729 O-linked 722:729 O-linked 722:729 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 21 theme glycan 688:693 arg1 4 681:681 4 681:681 4 681:681 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 21 theme glycan 688:693 arg1 chains 695:700 the glycan chains 684:700 the glycan chains 684:700 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 22 theme H 878:878 arg1 type 880:883 H type 2 878:885 H type 2 878:885 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 23 contain carry 832:836 arg2 structures 900:909 fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures 838:909 fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures 838:909 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 23 contain carry 832:836 arg1 chains 825:830 these chains 819:830 these chains 819:830 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 24 from threonine 593:601 arg1 rich 577:580 rich 577:580 rich 577:580 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 25 theme mucin-type 404:413 arg1 glycoprotein 415:426 a mucin-type glycoprotein 402:426 a mucin-type glycoprotein 402:426 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 1 26 theme affinity 304:311 arg1 chromatography 313:326 affinity chromatography 304:326 affinity chromatography 304:326 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 5 27 theme peptide 1452:1458 arg1 backbone 1460:1467 the peptide backbone 1448:1467 the peptide backbone 1448:1467 Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis. 9180155 1 28 theme new 147:149 arg1 MAb 179:181 MAb VK-8 179:186 MAb VK-8 179:186 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 1 28 theme new 147:149 arg1 antibody 169:176 A new murine monoclonal antibody 145:176 A new murine monoclonal antibody (MAb VK-8) 145:187 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 2 29 theme many 620:623 arg1 serine 585:590 serine 585:590 serine 585:590 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 1 30 theme murine 151:156 arg1 MAb 179:181 MAb VK-8 179:186 MAb VK-8 179:186 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 1 30 theme murine 151:156 arg1 antibody 169:176 A new murine monoclonal antibody 145:176 A new murine monoclonal antibody (MAb VK-8) 145:187 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 4 31 theme MAb 1193:1195 arg1 antibodies 1216:1225 OC125, the original MAb to CA125, and VK-8 antibodies 1173:1225 OC125, the original MAb to CA125, and VK-8 antibodies 1173:1225 Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. 9180155 4 32 from epitopes 1234:1241 arg1 portion 1258:1264 the protein portion 1246:1264 the protein portion of the molecule 1246:1280 Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. 9180155 2 33 theme group 894:898 arg1 structures 900:909 fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures 838:909 fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures 838:909 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 1 34 theme monoclonal 158:167 arg1 MAb 179:181 MAb VK-8 179:186 MAb VK-8 179:186 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 1 34 theme monoclonal 158:167 arg1 antibody 169:176 A new murine monoclonal antibody 145:176 A new murine monoclonal antibody (MAb VK-8) 145:187 A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. 9180155 5 35 theme structural 1506:1515 arg1 analysis 1517:1524 more detailed carbohydrate structural analysis 1479:1524 more detailed carbohydrate structural analysis 1479:1524 Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis. 9180155 2 36 theme blood 888:892 arg1 structures 900:909 fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures 838:909 fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures 838:909 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 37 theme antigen 372:378 arg1 properties 345:354 The biochemical properties 329:354 The biochemical properties of the purified antigen 329:378 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 37 theme antigen 372:378 arg1 characteristic 384:397 characteristic 384:397 characteristic 384:397 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 38 theme --> 754:756 arg1 [Galbeta1 744:752 core 2 [Galbeta1 --> 3 737:758 core 2 [Galbeta1 --> 3 737:758 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 3 39 theme smaller 1046:1052 arg1 fragments 1054:1062 smaller fragments 1046:1062 smaller fragments that no longer reacted with the antibody 1046:1103 The antigen exhibited a very high m.w. (> 10(3) kDa) in aqueous buffer as well as in urea, but was degraded by proteolytic enzymes to smaller fragments that no longer reacted with the antibody. 9180155 2 40 theme fucosylated 838:848 arg1 Type 850:853 fucosylated Type 2 838:855 fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures 838:909 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 41 theme threonine 643:651 arg1 residues 653:660 the serine and threonine residues 628:660 residues 653:660 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 42 theme purified 363:370 arg1 antigen 372:378 the purified antigen 359:378 the purified antigen 359:378 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 0 43 theme cancer 42:47 arg1 CA 57:58 ovarian cancer antigen CA 125 34:62 ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8) 34:101 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 2 44 theme % 472:472 arg1 w/w 474:476 77% w/w 470:476 77% w/w 470:476 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 4 45 theme carbohydrate 1302:1313 arg1 involvement 1287:1297 the involvement 1283:1297 the involvement of carbohydrate 1283:1313 Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. 9180155 3 46 theme aqueous 968:974 arg1 buffer 976:981 aqueous buffer 968:981 aqueous buffer 968:981 The antigen exhibited a very high m.w. (> 10(3) kDa) in aqueous buffer as well as in urea, but was degraded by proteolytic enzymes to smaller fragments that no longer reacted with the antibody. 9180155 0 47 theme ovarian 34:40 arg1 CA 57:58 ovarian cancer antigen CA 125 34:62 ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8) 34:101 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 2 48 dep carry 832:836 arg1 5 816:816 5 816:816 5 816:816 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 49 dep glycosylated 456:467 arg1 w/w 474:476 77% w/w 470:476 77% w/w 470:476 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 49 dep glycosylated 456:467 arg1 rich 577:580 rich 577:580 rich 577:580 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 49 dep glycosylated 456:467 arg1 2 552:552 2 552:552 2 552:552 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 5 50 theme detailed 1484:1491 arg1 analysis 1517:1524 more detailed carbohydrate structural analysis 1479:1524 more detailed carbohydrate structural analysis 1479:1524 Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis. 9180155 5 51 theme Further 1336:1342 arg1 insight 1344:1350 Further insight 1336:1350 Further insight into the structure and function of the CA125 antigen 1336:1403 Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis. 9180155 0 52 theme CA 57:58 arg1 characterization 14:29 characterization 14:29 characterization 14:29 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 0 52 theme CA 57:58 arg1 Isolation 0:8 Isolation 0:8 Isolation 0:8 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 3 53 theme high 941:944 arg1 kDa 960:962 > 10(3) kDa 952:962 > 10(3) kDa 952:962 The antigen exhibited a very high m.w. (> 10(3) kDa) in aqueous buffer as well as in urea, but was degraded by proteolytic enzymes to smaller fragments that no longer reacted with the antibody. 9180155 3 53 theme high 941:944 arg1 m.w. 946:949 a very high m.w. 934:949 a very high m.w. (> 10(3) kDa) 934:963 The antigen exhibited a very high m.w. (> 10(3) kDa) in aqueous buffer as well as in urea, but was degraded by proteolytic enzymes to smaller fragments that no longer reacted with the antibody. 9180155 0 54 theme mucin-type 124:133 arg1 molecule 135:142 a mucin-type molecule 122:142 a mucin-type molecule 122:142 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 5 55 theme carbohydrate 1493:1504 arg1 analysis 1517:1524 more detailed carbohydrate structural analysis 1479:1524 more detailed carbohydrate structural analysis 1479:1524 Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis. 9180155 5 56 theme CA125 1391:1395 arg1 antigen 1397:1403 the CA125 antigen 1387:1403 the CA125 antigen 1387:1403 Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis. 9180155 0 57 theme antigen 49:55 arg1 CA 57:58 ovarian cancer antigen CA 125 34:62 ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8) 34:101 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 2 58 dep predominating 797:809 arg1 1 430:430 1 430:430 1 430:430 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 5 59 dep structure 1361:1369 arg1 the 1357:1359 the 1357:1359 the 1357:1359 Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis. 9180155 2 60 gly glycoprotein 415:426 arg1 glycoprotein 415:426 a mucin-type glycoprotein 402:426 a mucin-type glycoprotein 402:426 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 5 61 theme antigen 1397:1403 arg1 function 1375:1382 function 1375:1382 function 1375:1382 Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis. 9180155 5 61 theme antigen 1397:1403 arg1 structure 1361:1369 structure 1361:1369 structure 1361:1369 Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis. 9180155 2 62 theme GlcNAcbeta1 760:770 arg1 --> 772:774 GlcNAcbeta1 --> 6 760:776 GlcNAcbeta1 --> 6 760:776 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 62 theme GlcNAcbeta1 760:770 arg1 molecule 437:444 the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3 433:758 the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures 433:795 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 63 dep molecule 437:444 arg1 moiety 567:572 the protein moiety 555:572 the protein moiety 555:572 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 63 dep molecule 437:444 arg1 glycosylated 456:467 glycosylated 456:467 glycosylated 456:467 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 64 from proline 607:613 arg1 rich 577:580 rich 577:580 rich 577:580 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 65 gly glycosylated 666:677 arg1 residues 653:660 the serine and threonine residues 628:660 residues 653:660 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 4 66 theme molecule 1273:1280 arg1 portion 1258:1264 the protein portion 1246:1264 the protein portion of the molecule 1246:1280 Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. 9180155 4 67 theme VK-8 1211:1214 arg1 antibodies 1216:1225 OC125, the original MAb to CA125, and VK-8 antibodies 1173:1225 OC125, the original MAb to CA125, and VK-8 antibodies 1173:1225 Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. 9180155 2 68 dep Type 850:853 arg1 type 880:883 H type 2 878:885 H type 2 878:885 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 68 dep Type 850:853 arg1 x 871:871 x 871:871 x 871:871 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 68 dep Type 850:853 arg1 y 861:861 y 861:861 y 861:861 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 68 dep Type 850:853 arg1 Le 868:869 Le 868:869 Le 868:869 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 68 dep Type 850:853 arg1 Le 858:859 Le 858:859 Le(y) 858:862 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 69 theme molecule 437:444 arg1 structures 786:795 the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures 433:795 the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures 433:795 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 70 theme Type 850:853 arg1 structures 900:909 fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures 838:909 fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures 838:909 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 71 from rich 577:580 arg1 proline 607:613 proline 607:613 proline 607:613 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 71 from rich 577:580 arg1 threonine 593:601 threonine 593:601 threonine 593:601 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 71 from rich 577:580 arg1 serine 585:590 serine 585:590 serine 585:590 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 72 theme biochemical 333:343 arg1 properties 345:354 The biochemical properties 329:354 The biochemical properties of the purified antigen 329:378 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 72 theme biochemical 333:343 arg1 characteristic 384:397 characteristic 384:397 characteristic 384:397 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 4 73 theme other 1132:1136 arg1 data 1153:1156 other immunochemical data 1132:1156 other immunochemical data 1132:1156 Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. 9180155 2 74 theme glycoprotein 415:426 arg1 properties 345:354 The biochemical properties 329:354 The biochemical properties of the purified antigen 329:378 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 2 74 theme glycoprotein 415:426 arg1 characteristic 384:397 characteristic 384:397 characteristic 384:397 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 4 75 theme immunochemical 1138:1151 arg1 data 1153:1156 other immunochemical data 1132:1156 other immunochemical data 1132:1156 Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. 9180155 0 76 dep Isolation 0:8 arg1 identification 104:117 identification 104:117 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 0:143 Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 9180155 2 77 theme GalNAc 778:783 arg1 structures 786:795 the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures 433:795 the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures 433:795 The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. 9180155 4 78 theme original 1184:1191 arg1 MAb 1193:1195 the original MAb 1180:1195 the original MAb to CA125 1180:1204 Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. 1726196 3 0 theme 1----3 1034:1039 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 0 theme 1----3 1034:1039 arg1 -beta-Gal- 1180:1189 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 0 theme 1----3 1034:1039 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 1 theme -beta-Gal- 1062:1071 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 1 theme -beta-Gal- 1062:1071 arg1 -beta-Gal- 1180:1189 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 1 theme -beta-Gal- 1062:1071 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 2 2 theme methylation 701:711 arg1 analysis 713:720 methylation analysis 701:720 methylation analysis 701:720 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 3 3 theme 1----3 1055:1060 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 3 theme 1----3 1055:1060 arg1 -beta-Gal- 1180:1189 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 3 theme 1----3 1055:1060 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 4 theme -GalNAcol 1080:1088 arg1 -GalNAcol 1221:1229 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1024:1229 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1024:1229 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 5 theme oligosaccharides 813:828 arg1 those 848:852 those 848:852 those 848:852 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 5 theme oligosaccharides 813:828 arg1 array 804:808 an array 801:808 an array of oligosaccharides characterised 801:842 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 6 theme 1----3 1073:1078 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 6 theme 1----3 1073:1078 arg1 -beta-Gal- 1180:1189 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 6 theme 1----3 1073:1078 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 0 7 theme derivatives 143:153 arg1 microsequencing 110:124 t.l.c.-m.s. microsequencing 98:124 t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy 98:218 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 1 8 theme treated 421:427 arg1 group 435:439 mild-acid treated blood group 411:439 mild-acid treated blood group 411:439 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 0 9 theme conventional 175:186 arg1 spectroscopy 207:218 conventional m.s. and 1H-n.m.r. spectroscopy 175:218 conventional m.s. and 1H-n.m.r. spectroscopy 175:218 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 3 10 theme -GalNAcol 914:922 arg1 core 924:927 the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 861:1532 core 924:927 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 0 11 with conjunction 158:168 arg1 spectroscopy 207:218 conventional m.s. and 1H-n.m.r. spectroscopy 175:218 conventional m.s. and 1H-n.m.r. spectroscopy 175:218 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 3 12 with core 924:927 arg1 sequences 967:975 linear sequences 960:975 the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 946:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 13 theme branched 865:872 arg1 [beta-Gal- 894:903 the branched beta-GlcNAc-(1----6)[beta-Gal- 861:903 the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3) 861:912 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 13 theme branched 865:872 arg1 1----3 906:911 1----3 906:911 1----3 906:911 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 0 14 theme human 66:70 arg1 glycoproteins 81:93 human meconium glycoproteins 66:93 human meconium glycoproteins 66:93 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 2 15 theme oligosaccharides 777:792 arg1 spectroscopy 687:698 1H-n.m.r. spectroscopy 677:698 1H-n.m.r. spectroscopy 677:698 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 2 15 theme oligosaccharides 777:792 arg1 analysis 713:720 methylation analysis 701:720 methylation analysis 701:720 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 2 15 theme oligosaccharides 777:792 arg1 m.s. 746:749 m.s. 746:749 m.s. 746:749 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 2 15 theme oligosaccharides 777:792 arg1 spectrometry 732:743 mass spectrometry 727:743 mass spectrometry 727:743 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 3 16 theme beta-Gal- 1306:1314 arg1 -GalNAcol 1406:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 17 theme tetra- 369:374 arg1 part 224:227 part 224:227 part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins 224:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 17 theme tetra- 369:374 arg1 glycoproteins 462:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 0 18 from microsequencing 110:124 arg1 conjunction 158:168 conjunction 158:168 conjunction with conventional m.s. and 1H-n.m.r. spectroscopy 158:218 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 2 19 theme microsequencing 580:594 arg1 procedure 596:604 a t.l.c.-m.s. microsequencing procedure 566:604 a t.l.c.-m.s. microsequencing procedure 566:604 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 3 20 theme 1----3 1339:1344 arg1 -GalNAcol 1406:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 0 21 theme t.l.c.-m.s. 98:108 arg1 microsequencing 110:124 t.l.c.-m.s. microsequencing 98:124 t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy 98:218 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 3 22 theme beta-Gal- 1091:1099 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 22 theme beta-Gal- 1091:1099 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 23 theme linear 960:965 arg1 sequences 967:975 linear sequences 960:975 the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 946:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 24 theme -beta-GlcNAc- 1325:1337 arg1 -GalNAcol 1406:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 25 theme 1----3 1122:1127 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 25 theme 1----3 1122:1127 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 26 theme -beta-GlcNAc- 1108:1120 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 26 theme -beta-GlcNAc- 1108:1120 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 27 theme -beta-Gal- 1346:1355 arg1 -GalNAcol 1406:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 28 theme oligosaccharides 309:324 arg1 sequences 287:295 core and backbone sequences 269:295 sequences 287:295 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 29 theme 1----3 1140:1145 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 29 theme 1----3 1140:1145 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 30 theme human 329:333 arg1 glycoproteins 344:356 human meconium glycoproteins 329:356 human meconium glycoproteins 329:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 31 theme -beta-Gal- 1129:1138 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 31 theme -beta-Gal- 1129:1138 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 32 theme -beta- 1366:1371 arg1 -GalNAcol 1406:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 33 theme glycoproteins 344:356 arg1 oligosaccharides 309:324 O-linked oligosaccharides 300:324 O-linked oligosaccharides of human meconium glycoproteins 300:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 34 theme alpha-GalNAc- 1158:1170 arg1 -beta-Gal- 1180:1189 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 34 theme alpha-GalNAc- 1158:1170 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 35 attach released 397:404 arg1 group 435:439 mild-acid treated blood group 411:439 mild-acid treated blood group 411:439 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 35 attach released 397:404 arg2 hepta-saccharides 379:395 hepta-saccharides 379:395 hepta-saccharides released from mild-acid treated blood group 379:439 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 36 theme base 260:263 arg1 establishment 236:248 the establishment 232:248 the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins 232:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 37 link O-linked 300:307 arg1 oligosaccharides 309:324 O-linked oligosaccharides 300:324 O-linked oligosaccharides of human meconium glycoproteins 300:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 38 theme core 269:272 arg1 sequences 287:295 core and backbone sequences 269:295 sequences 287:295 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 39 theme 1----3 1173:1178 arg1 -beta-Gal- 1180:1189 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 39 theme 1----3 1173:1178 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 40 gly glycoproteins 462:474 arg1 part 224:227 part 224:227 part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins 224:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 40 gly glycoproteins 462:474 arg1 glycoproteins 462:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 41 theme backbone 278:285 arg1 sequences 287:295 core and backbone sequences 269:295 sequences 287:295 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 42 theme -beta-GlcNAc- 1200:1212 arg1 -GalNAcol 1221:1229 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1024:1229 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1024:1229 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 43 dep source 1016:1021 arg1 -GalNAcol 1221:1229 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1024:1229 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1024:1229 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 2 44 with conjunction 660:670 arg1 spectroscopy 687:698 1H-n.m.r. spectroscopy 677:698 1H-n.m.r. spectroscopy 677:698 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 2 44 with conjunction 660:670 arg1 analysis 713:720 methylation analysis 701:720 methylation analysis 701:720 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 2 44 with conjunction 660:670 arg1 m.s. 746:749 m.s. 746:749 m.s. 746:749 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 2 44 with conjunction 660:670 arg1 spectrometry 732:743 mass spectrometry 727:743 mass spectrometry 727:743 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 3 45 with others 934:939 arg1 sequences 967:975 linear sequences 960:975 the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 946:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 2 46 theme 1H-n.m.r. 677:685 arg1 spectroscopy 687:698 1H-n.m.r. spectroscopy 677:698 1H-n.m.r. spectroscopy 677:698 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 2 46 theme 1H-n.m.r. 677:685 arg1 m.s. 746:749 m.s. 746:749 m.s. 746:749 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 3 47 theme 1----3 1214:1219 arg1 -GalNAcol 1221:1229 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1024:1229 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1024:1229 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 48 theme blood 429:433 arg1 group 435:439 mild-acid treated blood group 411:439 mild-acid treated blood group 411:439 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 49 theme establishment 236:248 arg1 part 224:227 part 224:227 part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins 224:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 49 theme establishment 236:248 arg1 glycoproteins 462:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 50 theme 1----3 1246:1251 arg1 -beta-Gal- 1253:1262 beta-GlcNAc- (1----3)-beta-Gal- 1232:1262 beta-GlcNAc- (1----3)-beta-Gal- 1232:1262 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 50 theme 1----3 1246:1251 arg1 source 1016:1021 this source 1011:1021 this source 1011:1021 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 2 51 theme methylated 766:775 arg1 oligosaccharides 777:792 native and methylated oligosaccharides 755:792 native and methylated oligosaccharides 755:792 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 3 52 theme -beta-GlcNAc- 1273:1285 arg1 1----3/4 1264:1271 1----3/4 1264:1271 1----3/4 1264:1271 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 52 theme -beta-GlcNAc- 1273:1285 arg1 source 1016:1021 this source 1011:1021 this source 1011:1021 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 52 theme -beta-GlcNAc- 1273:1285 arg1 1----3 1287:1292 1----3 1287:1292 1----3 1287:1292 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 52 theme -beta-GlcNAc- 1273:1285 arg1 -beta-Gal- 1253:1262 beta-GlcNAc- (1----3)-beta-Gal- 1232:1262 beta-GlcNAc- (1----3)-beta-Gal- 1232:1262 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 0 53 theme m.s. 188:191 arg1 spectroscopy 207:218 conventional m.s. and 1H-n.m.r. spectroscopy 175:218 conventional m.s. and 1H-n.m.r. spectroscopy 175:218 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 1 54 theme [corrected 441:450 arg1 part 224:227 part 224:227 part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins 224:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 54 theme [corrected 441:450 arg1 glycoproteins 462:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 55 theme beta-GlcNAc- 1232:1243 arg1 -beta-Gal- 1253:1262 beta-GlcNAc- (1----3)-beta-Gal- 1232:1262 beta-GlcNAc- (1----3)-beta-Gal- 1232:1262 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 55 theme beta-GlcNAc- 1232:1243 arg1 source 1016:1021 this source 1011:1021 this source 1011:1021 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 2 56 theme neoglycolipid 630:642 arg1 derivatives 644:654 the neoglycolipid derivatives 626:654 the neoglycolipid derivatives 626:654 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 3 57 theme 1----3 1434:1439 arg1 -GalNAcol 1524:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 2 58 theme native 755:760 arg1 oligosaccharides 777:792 native and methylated oligosaccharides 755:792 native and methylated oligosaccharides 755:792 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 0 59 theme 1H-n.m.r. 197:205 arg1 spectroscopy 207:218 conventional m.s. and 1H-n.m.r. spectroscopy 175:218 conventional m.s. and 1H-n.m.r. spectroscopy 175:218 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 1 60 theme H-active 453:460 arg1 part 224:227 part 224:227 part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins 224:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 60 theme H-active 453:460 arg1 glycoproteins 462:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 61 dep sequences 967:975 arg1 characterised 981:993 characterised 981:993 not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 977:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 62 theme beta-GlcNAc- 1421:1432 arg1 -GalNAcol 1524:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 63 theme 1----6 887:892 arg1 [beta-Gal- 894:903 the branched beta-GlcNAc-(1----6)[beta-Gal- 861:903 the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3) 861:912 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 63 theme 1----6 887:892 arg1 1----3 906:911 1----3 906:911 1----3 906:911 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 0 64 theme meconium 72:79 arg1 glycoproteins 81:93 human meconium glycoproteins 66:93 human meconium glycoproteins 66:93 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 3 65 theme beta-GlcNAc- 874:885 arg1 [beta-Gal- 894:903 the branched beta-GlcNAc-(1----6)[beta-Gal- 861:903 the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3) 861:912 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 65 theme beta-GlcNAc- 874:885 arg1 1----3 906:911 1----3 906:911 1----3 906:911 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 66 theme minor 363:367 arg1 part 224:227 part 224:227 part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins 224:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 66 theme minor 363:367 arg1 glycoproteins 462:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins 359:474 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 1 67 gly glycoproteins 344:356 arg1 glycoproteins 344:356 human meconium glycoproteins 329:356 human meconium glycoproteins 329:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 68 theme -beta-Gal- 1441:1450 arg1 -GalNAcol 1524:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 2 69 theme mass 727:730 arg1 spectrometry 732:743 mass spectrometry 727:743 mass spectrometry 727:743 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 2 70 theme t.l.c.-m.s. 568:578 arg1 procedure 596:604 a t.l.c.-m.s. microsequencing procedure 566:604 a t.l.c.-m.s. microsequencing procedure 566:604 These oligosaccharides are heterogeneous and difficult to isolate, and a t.l.c.-m.s. microsequencing procedure has been applied to the neoglycolipid derivatives, in conjunction with 1H-n.m.r. spectroscopy, methylation analysis, and mass spectrometry (m.s.) of native and methylated oligosaccharides. 1726196 3 71 theme 1----3 1475:1480 arg1 -GalNAcol 1524:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 72 theme [beta-Gal- 894:903 arg1 core 924:927 the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 861:1532 core 924:927 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 0 73 theme neoglycolipid 129:141 arg1 derivatives 143:153 neoglycolipid derivatives 129:153 neoglycolipid derivatives 129:153 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 0 74 gly glycoproteins 81:93 arg1 glycoproteins 81:93 human meconium glycoproteins 66:93 human meconium glycoproteins 66:93 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 3 75 theme -beta-GlcNAc- 1461:1473 arg1 -GalNAcol 1524:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 76 contain having 854:859 arg1 those 848:852 those 848:852 those 848:852 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 76 contain having 854:859 arg1 array 804:808 an array 801:808 an array of oligosaccharides characterised 801:842 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 76 contain having 854:859 arg2 others 934:939 others 934:939 others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 934:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 76 contain having 854:859 arg2 core 924:927 the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 861:1532 core 924:927 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 77 theme mild-acid 411:419 arg1 group 435:439 mild-acid treated blood group 411:439 mild-acid treated blood group 411:439 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 78 theme following 950:958 arg1 sequences 967:975 linear sequences 960:975 the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 946:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 0 79 theme tetra- 26:31 arg1 Characterisation 0:15 Characterisation 0:15 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 0:219 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 1 80 theme O-linked 300:307 arg1 oligosaccharides 309:324 O-linked oligosaccharides 300:324 O-linked oligosaccharides of human meconium glycoproteins 300:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 81 theme -beta-Gal- 1482:1491 arg1 -GalNAcol 1524:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 82 theme 1----3 1517:1522 arg1 -GalNAcol 1524:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 83 theme 1----3 1381:1386 arg1 -GalNAcol 1406:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 84 theme meconium 335:342 arg1 glycoproteins 344:356 human meconium glycoproteins 329:356 human meconium glycoproteins 329:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 0 85 dep hepta-saccharides 36:52 arg1 O-linked 54:61 O-linked 54:61 O-linked 54:61 Characterisation of minor tetra- to hepta-saccharides O-linked to human meconium glycoproteins by t.l.c.-m.s. microsequencing of neoglycolipid derivatives in conjunction with conventional m.s. and 1H-n.m.r. spectroscopy. 1726196 3 86 theme beta-Gal- 1024:1032 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 86 theme beta-Gal- 1024:1032 arg1 -beta-Gal- 1180:1189 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 86 theme beta-Gal- 1024:1032 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 87 theme -beta-GlcNAc- 1503:1515 arg1 -GalNAcol 1524:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol 1421:1532 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 88 theme GlcNAc- 1373:1379 arg1 -GalNAcol 1406:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 89 theme 1----3 1399:1404 arg1 -GalNAcol 1406:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 1 90 theme data 255:258 arg1 base 260:263 a data base 253:263 a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins 253:356 As part of the establishment of a data base for core and backbone sequences of O-linked oligosaccharides of human meconium glycoproteins, the minor tetra- to hepta-saccharides released from mild-acid treated blood group [corrected] H-active glycoproteins have been studied. 1726196 3 91 theme -beta-GlcNAc- 1041:1053 arg1 -GalNAcol 1147:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1091:1155 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 91 theme -beta-GlcNAc- 1041:1053 arg1 -beta-Gal- 1180:1189 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 alpha-GalNAc- (1----3)-beta-Gal-(1----3/4) 1158:1199 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 91 theme -beta-GlcNAc- 1041:1053 arg1 -GalNAcol 1080:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1024:1088 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol. 1726196 3 92 theme -beta-Gal- 1388:1397 arg1 -GalNAcol 1406:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol 1306:1414 Among an array of oligosaccharides characterised are those having the branched beta-GlcNAc-(1----6)[beta-Gal- (1----3)]-GalNAcol core, and others with the following linear sequences not characterised previously from this source: beta-Gal-(1----3)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, beta-Gal-(1----4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, alpha-GalNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-GalNAcol, beta-GlcNAc- (1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)- GalNAcol, beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta- GlcNAc-(1----3)-beta-Gal-(1----3)-GalNAcol, and beta-GlcNAc-(1----3)-beta-Gal-(1----3/4)-beta-GlcNAc-(1----3)-beta-Gal- (1----3/4)-beta-GlcNAc-(1----3)-GalNAcol.